Title: WHO / Skin
Tags: Skin::Neoplastic::Soft_Tissue Skin::Neoplastic::Melanocytic Skin::Neoplastic::Hematolymphoid Skin::Neoplastic::Adnexal Skin::Neoplastic::Epidermal Skin::Neoplastic::Uncertain Skin::Infectious::Viral Skin::Depositional_Metabolic::Xanthoma Skin::Neoplastic::Metastatic Skin::Inflammatory::Granulomatous Skin::Syndromes::Muir_Torre_Syndrome Skin::Congenital_Structural::Cyst Skin::Inflammatory::Photosensitivity Skin::Inflammatory::Reactive Skin::Syndromes::Carney_Complex

Q: Clinically, Hidrocystoma/cystadenoma typically presents on the face as a solitary, translucent, and characteristically [...] cystic lesion.
Hidrocystoma/cystadenoma. Clinically, the lesion appears as a solitary, bluish to black, small dome-shaped papule.
Hidrocystoma/cystadenoma. Dermoscopy of a hidrocystoma.
A: bluish
Back Extra: Hidrocystoma/cystadenoma
- Clinical: Hidrocystomas are solitary, asymptomatic, bluish, cystic, and translucent lesions, usually located on the face, and they can vary in size from 5–10 mm to 70 mm.
- Micro: Hidrocystomas typically present as round to oval cystic structures lined by columnar epithelium with abundant mucin in the lumen.
- Ancillary: Luminal cells are positive for EMA and CEA, while myoepithelial elements are immunoreactive for S100, SOX10, and p63.
Reference Gallery:
Hidrocystoma. A cystic tumour containing large amounts of mucin.
Hidrocystoma. Detail of the cuboidal epithelium lining the cystic spaces.
Hidrocystoma/cystadenoma. Clinically, the lesion appears as a solitary, bluish to black, small dome-shaped papule.
Hidrocystoma/cystadenoma. Dermoscopy of a hidrocystoma.

Q: Microscopically, Hidrocystoma/cystadenoma presents as round to oval cystic structures lined by columnar or cuboidal epithelium, with the lumen frequently containing abundant [...].
Hidrocystoma. A cystic tumour containing large amounts of mucin.
Hidrocystoma. Detail of the cuboidal epithelium lining the cystic spaces.
A: mucin
Back Extra: Hidrocystoma/cystadenoma
- Clinical: Hidrocystomas are solitary, asymptomatic, bluish, cystic, and translucent lesions, usually located on the face, and they can vary in size from 5–10 mm to 70 mm.
- Micro: Hidrocystomas typically present as round to oval cystic structures lined by columnar epithelium with abundant mucin in the lumen.
- Ancillary: Luminal cells are positive for EMA and CEA, while myoepithelial elements are immunoreactive for S100, SOX10, and p63.
Reference Gallery:
Hidrocystoma. A cystic tumour containing large amounts of mucin.
Hidrocystoma. Detail of the cuboidal epithelium lining the cystic spaces.
Hidrocystoma/cystadenoma. Clinically, the lesion appears as a solitary, bluish to black, small dome-shaped papule.
Hidrocystoma/cystadenoma. Dermoscopy of a hidrocystoma.

Q: Histologically, Xanthelasma is characterized by dermal collections of [...] that often cluster around blood vessels and adnexal structures in the eyelid.
Xanthelasma. Eyelid skin comprising collections of foamy histiocytes in the dermis, associated with some patchy collections of lymphocytes around the vessels. Note how the foamy histiocytes peter out towards the deeper aspect of the biopsy.
A: lipid-laden (foamy) histiocytes
Back Extra: Xanthelasma
- Clinical: Xanthelasma appears as flat or minimally elevated yellow lesions, commonly in the medial aspect of the eyelids, often bilateral and symmetrical.
- Micro: Xanthelasma shows focal collections of lipid-laden histiocytes distributed mainly around blood vessels and adnexal structures in the eyelid dermis, with chronic inflammation and fibrosis.
- Ancillary: The foamy histiocytes typically express CD68, CD163, and factor XIIIa, but lack CD21, CD35, S100, CD1a, and Birbeck granules.
Reference Gallery:
Xanthelasma. Eyelid skin comprising collections of foamy histiocytes in the dermis, associated with some patchy collections of lymphocytes around the vessels. Note how the foamy histiocytes peter out towards the deeper aspect of the biopsy.
Xanthelasma. Higher-power image showing the frothy/foamy cytoplasm of the histiocytes and small bland nuclei.

Q: On high-power microscopic examination of Xanthelasma, the characteristic histiocytes display small, bland nuclei and abundant, frothy or [...] cytoplasm.
Xanthelasma. Higher-power image showing the frothy/foamy cytoplasm of the histiocytes and small bland nuclei.
A: foamy
Back Extra: Xanthelasma
- Clinical: Xanthelasma appears as flat or minimally elevated yellow lesions, commonly in the medial aspect of the eyelids, often bilateral and symmetrical.
- Micro: Xanthelasma shows focal collections of lipid-laden histiocytes distributed mainly around blood vessels and adnexal structures in the eyelid dermis, with chronic inflammation and fibrosis.
- Ancillary: The foamy histiocytes typically express CD68, CD163, and factor XIIIa, but lack CD21, CD35, S100, CD1a, and Birbeck granules.
Reference Gallery:
Xanthelasma. Eyelid skin comprising collections of foamy histiocytes in the dermis, associated with some patchy collections of lymphocytes around the vessels. Note how the foamy histiocytes peter out towards the deeper aspect of the biopsy.
Xanthelasma. Higher-power image showing the frothy/foamy cytoplasm of the histiocytes and small bland nuclei.

Q: In Juvenile Xanthogranuloma, the characteristic histologic finding is a dermal infiltrate of macrophages featuring multinucleated [...], which have a wreath of nuclei surrounding a homogeneous eosinophilic center and a xanthomatized periphery.
Juvenile xanthogranuloma. Below a grenz zone, there is a diffuse dermal infiltrate of eye-catching Touton giant cells characterized by a wreath of nuclei around a homogeneous eosinophilic centre, with a strongly xanthomatized periphery. Also note the mononuclear macrophages, dominated by xanthomatized cells, less prominent vacuolated cells, and scalloped cells.
Juvenile xanthogranuloma. Below a grenz zone, there is an infiltrate of monomorphic, xanthomatized macrophages, including plentiful Touton giant cells intermingled with a moderate number of lymphocytes. This type of monomorphic lesion is seen clinically as solitary/localized to generalized papular xanthoma, or in the late stages of xanthoma disseminatum. Xanthelasma, which is solitary or localized mostly around the eyelids, follows the same monomorphic xanthomatized reaction pattern, but usually with many fewer (or no) Touton giant cells.
A: Touton giant cells
Back Extra: Juvenile Xanthogranuloma
- Clinical: Juvenile xanthogranulomas typically present as asymptomatic macules, papules, or nodules in infants, often resolving spontaneously within months to years. In adults, lesions are usually larger and solitary.
- Micro: Histologically, juvenile xanthogranulomas are characterized by a dermal infiltrate of mononuclear macrophages, Touton giant cells, and varying degrees of xanthomatization and fibrosis.
- Ancillary: Macrophages in juvenile xanthogranulomas are positive for CD68, CD163, CD4, and CD14. Early lesions are also positive for factor XIIIa, and later spindly lesions express SMA and fascin.
Reference Gallery:
Juvenile xanthogranuloma. Below a grenz zone, there is a diffuse dermal infiltrate of eye-catching Touton giant cells characterized by a wreath of nuclei around a homogeneous eosinophilic centre, with a strongly xanthomatized periphery. Also note the mononuclear macrophages, dominated by xanthomatized cells, less prominent vacuolated cells, and scalloped cells.
Juvenile xanthogranuloma. Early juvenile xanthogranuloma, with mid-dermal to deep-dermal, ill-defined infiltrate of macrophages.
Xanthogranuloma, xanthomatized pattern. A dome-shaped to polypoid lesion of xanthogranuloma with a diffuse, ill-defined dermal infiltrate of mostly massively xanthomatized macrophages.
Juvenile xanthogranuloma. Below a grenz zone, there is an infiltrate of monomorphic, xanthomatized macrophages, including plentiful Touton giant cells intermingled with a moderate number of lymphocytes. This type of monomorphic lesion is seen clinically as solitary/localized to generalized papular xanthoma, or in the late stages of xanthoma disseminatum. Xanthelasma, which is solitary or localized mostly around the eyelids, follows the same monomorphic xanthomatized reaction pattern, but usually with many fewer (or no) Touton giant cells.
Xanthogranuloma, spindle cell pattern. A dome-shaped xanthogranuloma with an ill-defined, diffuse dermal infiltrate of macrophages.
Xanthogranuloma, spindle cell pattern. Xanthomatized, scalloped, and oncocytic cells are found mostly at the periphery of the lesion, while the central parts are dominated by monomorphic, spindle-shaped macrophages (which are positive for SMA, not shown) arranged in fascicles or a storiform pattern. This type of lesion is seen clinically either as a solitary (adult) xanthogranuloma or as a generalized lesion as part of the presentation of progressive nodular histiocytosis, namely prominent, dermal to subcutaneous, deep-seated nodules to tumours beside superficial more classic papules of xanthogranulomas.
Xanthogranuloma, solitary adult pattern. Below a grenz zone, a diffuse dermal infiltrate reveals multinucleate giant cells of (want-to-be) Touton character (mostly missing a xanthomatized rim), beside a polymorphous mixture of mononuclear vacuolated macrophages. Some of the peripheral macrophages are spindle-shaped, and the most prominent are homogeneously eosinophilic, scalloped to oncocytic macrophages.
Juvenile xanthogranuloma, disseminated. Brownish to focally yellowish papules.
Cutaneous juvenile xanthogranuloma. Extensive positive staining for factor XIIIa is typical.

Q: Early lesions of Juvenile Xanthogranuloma are typically characterized by an infiltrate of macrophages that are strongly positive for the immunohistochemical stain [...], in addition to broad macrophage markers such as CD68 and CD163.
Cutaneous juvenile xanthogranuloma. Extensive positive staining for factor XIIIa is typical.
A: factor XIIIa
Back Extra: Juvenile Xanthogranuloma
- Clinical: Juvenile xanthogranulomas typically present as asymptomatic macules, papules, or nodules in infants, often resolving spontaneously within months to years. In adults, lesions are usually larger and solitary.
- Micro: Histologically, juvenile xanthogranulomas are characterized by a dermal infiltrate of mononuclear macrophages, Touton giant cells, and varying degrees of xanthomatization and fibrosis.
- Ancillary: Macrophages in juvenile xanthogranulomas are positive for CD68, CD163, CD4, and CD14. Early lesions are also positive for factor XIIIa, and later spindly lesions express SMA and fascin.
Reference Gallery:
Juvenile xanthogranuloma. Below a grenz zone, there is a diffuse dermal infiltrate of eye-catching Touton giant cells characterized by a wreath of nuclei around a homogeneous eosinophilic centre, with a strongly xanthomatized periphery. Also note the mononuclear macrophages, dominated by xanthomatized cells, less prominent vacuolated cells, and scalloped cells.
Juvenile xanthogranuloma. Early juvenile xanthogranuloma, with mid-dermal to deep-dermal, ill-defined infiltrate of macrophages.
Xanthogranuloma, xanthomatized pattern. A dome-shaped to polypoid lesion of xanthogranuloma with a diffuse, ill-defined dermal infiltrate of mostly massively xanthomatized macrophages.
Juvenile xanthogranuloma. Below a grenz zone, there is an infiltrate of monomorphic, xanthomatized macrophages, including plentiful Touton giant cells intermingled with a moderate number of lymphocytes. This type of monomorphic lesion is seen clinically as solitary/localized to generalized papular xanthoma, or in the late stages of xanthoma disseminatum. Xanthelasma, which is solitary or localized mostly around the eyelids, follows the same monomorphic xanthomatized reaction pattern, but usually with many fewer (or no) Touton giant cells.
Xanthogranuloma, spindle cell pattern. A dome-shaped xanthogranuloma with an ill-defined, diffuse dermal infiltrate of macrophages.
Xanthogranuloma, spindle cell pattern. Xanthomatized, scalloped, and oncocytic cells are found mostly at the periphery of the lesion, while the central parts are dominated by monomorphic, spindle-shaped macrophages (which are positive for SMA, not shown) arranged in fascicles or a storiform pattern. This type of lesion is seen clinically either as a solitary (adult) xanthogranuloma or as a generalized lesion as part of the presentation of progressive nodular histiocytosis, namely prominent, dermal to subcutaneous, deep-seated nodules to tumours beside superficial more classic papules of xanthogranulomas.
Xanthogranuloma, solitary adult pattern. Below a grenz zone, a diffuse dermal infiltrate reveals multinucleate giant cells of (want-to-be) Touton character (mostly missing a xanthomatized rim), beside a polymorphous mixture of mononuclear vacuolated macrophages. Some of the peripheral macrophages are spindle-shaped, and the most prominent are homogeneously eosinophilic, scalloped to oncocytic macrophages.
Juvenile xanthogranuloma, disseminated. Brownish to focally yellowish papules.
Cutaneous juvenile xanthogranuloma. Extensive positive staining for factor XIIIa is typical.

Q: An infant presenting with asymptomatic, brownish to yellowish papules that typically resolve spontaneously over months to years is classic for [...].
Juvenile xanthogranuloma, disseminated. Brownish to focally yellowish papules.
A: Juvenile Xanthogranuloma
Back Extra: Juvenile Xanthogranuloma
- Clinical: Juvenile xanthogranulomas typically present as asymptomatic macules, papules, or nodules in infants, often resolving spontaneously within months to years. In adults, lesions are usually larger and solitary.
- Micro: Histologically, juvenile xanthogranulomas are characterized by a dermal infiltrate of mononuclear macrophages, Touton giant cells, and varying degrees of xanthomatization and fibrosis.
- Ancillary: Macrophages in juvenile xanthogranulomas are positive for CD68, CD163, CD4, and CD14. Early lesions are also positive for factor XIIIa, and later spindly lesions express SMA and fascin.
Reference Gallery:
Juvenile xanthogranuloma. Below a grenz zone, there is a diffuse dermal infiltrate of eye-catching Touton giant cells characterized by a wreath of nuclei around a homogeneous eosinophilic centre, with a strongly xanthomatized periphery. Also note the mononuclear macrophages, dominated by xanthomatized cells, less prominent vacuolated cells, and scalloped cells.
Juvenile xanthogranuloma. Early juvenile xanthogranuloma, with mid-dermal to deep-dermal, ill-defined infiltrate of macrophages.
Xanthogranuloma, xanthomatized pattern. A dome-shaped to polypoid lesion of xanthogranuloma with a diffuse, ill-defined dermal infiltrate of mostly massively xanthomatized macrophages.
Juvenile xanthogranuloma. Below a grenz zone, there is an infiltrate of monomorphic, xanthomatized macrophages, including plentiful Touton giant cells intermingled with a moderate number of lymphocytes. This type of monomorphic lesion is seen clinically as solitary/localized to generalized papular xanthoma, or in the late stages of xanthoma disseminatum. Xanthelasma, which is solitary or localized mostly around the eyelids, follows the same monomorphic xanthomatized reaction pattern, but usually with many fewer (or no) Touton giant cells.
Xanthogranuloma, spindle cell pattern. A dome-shaped xanthogranuloma with an ill-defined, diffuse dermal infiltrate of macrophages.
Xanthogranuloma, spindle cell pattern. Xanthomatized, scalloped, and oncocytic cells are found mostly at the periphery of the lesion, while the central parts are dominated by monomorphic, spindle-shaped macrophages (which are positive for SMA, not shown) arranged in fascicles or a storiform pattern. This type of lesion is seen clinically either as a solitary (adult) xanthogranuloma or as a generalized lesion as part of the presentation of progressive nodular histiocytosis, namely prominent, dermal to subcutaneous, deep-seated nodules to tumours beside superficial more classic papules of xanthogranulomas.
Xanthogranuloma, solitary adult pattern. Below a grenz zone, a diffuse dermal infiltrate reveals multinucleate giant cells of (want-to-be) Touton character (mostly missing a xanthomatized rim), beside a polymorphous mixture of mononuclear vacuolated macrophages. Some of the peripheral macrophages are spindle-shaped, and the most prominent are homogeneously eosinophilic, scalloped to oncocytic macrophages.
Juvenile xanthogranuloma, disseminated. Brownish to focally yellowish papules.
Cutaneous juvenile xanthogranuloma. Extensive positive staining for factor XIIIa is typical.

Q: Patients with Hydroa vacciniforme lymphoproliferative disorder classically present with recurring papulovesicular eruptions on sun-exposed skin that evolve into ulcers and pitted, [...] atrophic scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
A: varioliform
Back Extra: Hydroa vacciniforme lymphoproliferative disorder
- Clinical: Hydroa vacciniforme lymphoproliferative disorder is characterized by recurring papulovesicular eruptions on sun-exposed skin, evolving to blisters and ulcers, leading to varioliform atrophic scars. Seasonal variations are common, with lesions recurring in spring and summer.
- Micro: The skin shows epidermal reticular degeneration evolving to intraepidermal vesiculation and sometimes ulceration. A perivascular and periadnexal infiltrate of atypical small to medium-sized lymphoid cells is present in the dermis, often extending into the subcutis.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is required to demonstrate the presence of EBV, and many cases show CD8-positive cytotoxic T-cells expressing TIA1, granzyme B, or perforin.
Reference Gallery:
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas and non–sun-exposed areas (shown here). The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. Panniculitic form. In severe cases the lymphoid infiltrate is dense and diffuse, involving the dermis, subcutaneous tissue, and muscle. The atypical infiltrate surrounds blood vessels, with angiodestructive features.
Hydroa vacciniforme lymphoproliferative disorder. Panniculitic form. In severe cases the lymphoid infiltrate is dense and diffuse, involving the dermis, subcutaneous tissue, and muscle. The atypical infiltrate surrounds blood vessels, with angiodestructive features.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).

Q: Histologically, the characteristic epidermal finding in Hydroa vacciniforme lymphoproliferative disorder is intraepidermal spongiotic vesiculation often driven by [...] degeneration.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
A: reticular
Back Extra: Hydroa vacciniforme lymphoproliferative disorder
- Clinical: Hydroa vacciniforme lymphoproliferative disorder is characterized by recurring papulovesicular eruptions on sun-exposed skin, evolving to blisters and ulcers, leading to varioliform atrophic scars. Seasonal variations are common, with lesions recurring in spring and summer.
- Micro: The skin shows epidermal reticular degeneration evolving to intraepidermal vesiculation and sometimes ulceration. A perivascular and periadnexal infiltrate of atypical small to medium-sized lymphoid cells is present in the dermis, often extending into the subcutis.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is required to demonstrate the presence of EBV, and many cases show CD8-positive cytotoxic T-cells expressing TIA1, granzyme B, or perforin.
Reference Gallery:
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas and non–sun-exposed areas (shown here). The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. Panniculitic form. In severe cases the lymphoid infiltrate is dense and diffuse, involving the dermis, subcutaneous tissue, and muscle. The atypical infiltrate surrounds blood vessels, with angiodestructive features.
Hydroa vacciniforme lymphoproliferative disorder. Panniculitic form. In severe cases the lymphoid infiltrate is dense and diffuse, involving the dermis, subcutaneous tissue, and muscle. The atypical infiltrate surrounds blood vessels, with angiodestructive features.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).

Q: The diagnosis of Hydroa vacciniforme lymphoproliferative disorder requires demonstrating the presence of [...] within the atypical T-cell or NK-cell infiltrate, typically via in situ hybridization for EBER.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
A: Epstein-Barr virus (EBV)
Back Extra: Hydroa vacciniforme lymphoproliferative disorder
- Clinical: Hydroa vacciniforme lymphoproliferative disorder is characterized by recurring papulovesicular eruptions on sun-exposed skin, evolving to blisters and ulcers, leading to varioliform atrophic scars. Seasonal variations are common, with lesions recurring in spring and summer.
- Micro: The skin shows epidermal reticular degeneration evolving to intraepidermal vesiculation and sometimes ulceration. A perivascular and periadnexal infiltrate of atypical small to medium-sized lymphoid cells is present in the dermis, often extending into the subcutis.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is required to demonstrate the presence of EBV, and many cases show CD8-positive cytotoxic T-cells expressing TIA1, granzyme B, or perforin.
Reference Gallery:
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas and non–sun-exposed areas (shown here). The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed areas (shown here) and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated, with haemorrhagic crust and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. Panniculitic form. In severe cases the lymphoid infiltrate is dense and diffuse, involving the dermis, subcutaneous tissue, and muscle. The atypical infiltrate surrounds blood vessels, with angiodestructive features.
Hydroa vacciniforme lymphoproliferative disorder. Panniculitic form. In severe cases the lymphoid infiltrate is dense and diffuse, involving the dermis, subcutaneous tissue, and muscle. The atypical infiltrate surrounds blood vessels, with angiodestructive features.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).

Q: Patients presenting with clusters of smooth-surfaced, skin-colored to light-brown flat-topped papules, frequently on the face, hands, and shins, are classically exhibiting [...].
Verruca plana. A cluster of flat-topped pinkish papules is present.
A: Verruca plana
Back Extra: Verruca plana
- Clinical: Patients present with several smooth-surfaced, skin-coloured to light-brown papules, most frequently on the face, hands, and shins.
- Micro: Histologically, there is orthokeratosis, mild acanthosis, hypergranulosis, and scattered koilocytes in the upper third of the epidermis.
- Ancillary: Routine HPV subtyping is not indicated for the management of verruca plana.
Reference Gallery:
Verruca plana. The epidermis shows orthokeratosis, mild acanthosis, hypergranulosis, and a central aggregate of koilocytes.
Verruca plana. A cluster of flat-topped pinkish papules is present.

Q: Histologically, Verruca plana is characterized by mild acanthosis, orthokeratosis, hypergranulosis, and scattered [...] in the upper third of the epidermis.
Verruca plana. The epidermis shows orthokeratosis, mild acanthosis, hypergranulosis, and a central aggregate of koilocytes.
A: koilocytes
Back Extra: Verruca plana
- Clinical: Patients present with several smooth-surfaced, skin-coloured to light-brown papules, most frequently on the face, hands, and shins.
- Micro: Histologically, there is orthokeratosis, mild acanthosis, hypergranulosis, and scattered koilocytes in the upper third of the epidermis.
- Ancillary: Routine HPV subtyping is not indicated for the management of verruca plana.
Reference Gallery:
Verruca plana. The epidermis shows orthokeratosis, mild acanthosis, hypergranulosis, and a central aggregate of koilocytes.
Verruca plana. A cluster of flat-topped pinkish papules is present.

Q: In the myrmecial form of Verruca Plantaris and Verruca Palmaris, a pathognomonic histologic feature is the presence of coarse, inclusion-like [...] within the superficial keratinocytes.
Verruca plantaris. Coarse intracytoplasmic inclusion-like keratohyalin granules are present within the superficial keratinocytes.
A: keratohyalin granules
Back Extra: Verruca Plantaris and Verruca Palmaris
- Clinical: Verruca plantaris and Verruca palmaris are HPV-induced lesions, often presenting as painful, keratotic nodules on the soles or palms, with black dots reflecting intralesional vascular thrombosis.
- Micro: Characterized by marked hyperkeratosis, acanthosis, hypergranulosis, and koilocytosis. The myrmecial form shows endophytic growth with coarse eosinophilic keratohyalin granules in keratinocytes.
- Ancillary: Routine HPV subtyping is not indicated for Verruca plantaris and Verruca palmaris.
Reference Gallery:
Verruca plantaris. This myrmecial-type wart comprises a keratotic nodule on the sole of the foot and shows a surrounding blister.
Verruca plantaris. Partly endophytic and mildly papillomatous epidermal lesion, with marked hyperkeratosis and parakeratosis.
Verruca plantaris. Coarse intracytoplasmic inclusion-like keratohyalin granules are present within the superficial keratinocytes.

Q: Architecturally, the myrmecial variant of Verruca Plantaris and Verruca Palmaris is distinct due to its mildly papillomatous and predominantly [...] epidermal growth pattern accompanied by marked hyperkeratosis.
Verruca plantaris. Partly endophytic and mildly papillomatous epidermal lesion, with marked hyperkeratosis and parakeratosis.
A: endophytic
Back Extra: Verruca Plantaris and Verruca Palmaris
- Clinical: Verruca plantaris and Verruca palmaris are HPV-induced lesions, often presenting as painful, keratotic nodules on the soles or palms, with black dots reflecting intralesional vascular thrombosis.
- Micro: Characterized by marked hyperkeratosis, acanthosis, hypergranulosis, and koilocytosis. The myrmecial form shows endophytic growth with coarse eosinophilic keratohyalin granules in keratinocytes.
- Ancillary: Routine HPV subtyping is not indicated for Verruca plantaris and Verruca palmaris.
Reference Gallery:
Verruca plantaris. This myrmecial-type wart comprises a keratotic nodule on the sole of the foot and shows a surrounding blister.
Verruca plantaris. Partly endophytic and mildly papillomatous epidermal lesion, with marked hyperkeratosis and parakeratosis.
Verruca plantaris. Coarse intracytoplasmic inclusion-like keratohyalin granules are present within the superficial keratinocytes.

Q: Microscopically, Verruca Vulgaris features hyperkeratosis, papillomatosis, and characteristic HPV-altered cells with perinuclear halos known as [...].
Verruca vulgaris. The epidermal lesion shows hyperkeratosis, papillomatosis, and inward proliferation of the rete ridges.
Verruca vulgaris. Higher-magnification view highlighting the hypergranulosis and koilocytosis.
A: koilocytes
Back Extra: Verruca Vulgaris
- Clinical: Verruca vulgaris typically presents as single or multiple verrucous, keratotic papules or nodules, 1–20 mm in diameter, commonly on the hands and fingers.
- Micro: Microscopically, verruca vulgaris features hyperkeratosis, acanthosis, and papillomatosis with prominent, inwardly proliferating rete ridges and koilocytes.
- Ancillary: Routine HPV subtyping is not indicated in the management of verruca vulgaris.
Reference Gallery:
Verruca vulgaris. A keratotic nodule is present on the scalp.
Verruca vulgaris. The epidermal lesion shows hyperkeratosis, papillomatosis, and inward proliferation of the rete ridges.
Verruca vulgaris. Higher-magnification view highlighting the hypergranulosis and koilocytosis.

Q: A classic low-power architectural feature of Verruca Vulgaris is the prominent proliferation of rete ridges that characteristically point [...] toward the center of the lesion.
Verruca vulgaris. The epidermal lesion shows hyperkeratosis, papillomatosis, and inward proliferation of the rete ridges.
A: inwardly
Back Extra: Verruca Vulgaris
- Clinical: Verruca vulgaris typically presents as single or multiple verrucous, keratotic papules or nodules, 1–20 mm in diameter, commonly on the hands and fingers.
- Micro: Microscopically, verruca vulgaris features hyperkeratosis, acanthosis, and papillomatosis with prominent, inwardly proliferating rete ridges and koilocytes.
- Ancillary: Routine HPV subtyping is not indicated in the management of verruca vulgaris.
Reference Gallery:
Verruca vulgaris. A keratotic nodule is present on the scalp.
Verruca vulgaris. The epidermal lesion shows hyperkeratosis, papillomatosis, and inward proliferation of the rete ridges.
Verruca vulgaris. Higher-magnification view highlighting the hypergranulosis and koilocytosis.

Q: In cutaneous lesions of Inborn Error of Immunity-Associated Lymphoproliferative Disorders, a characteristic microscopic finding is a band-like, non-necrotizing confluent [...] infiltrate that is rich in CD8-positive T-cells.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. A band-like, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate is observed. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown in <<32513>>); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. A cytologically bland, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate is observed. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown in <<32513>>); and negative for infectious etiologies after extensive workup.
A: granulomatous
Back Extra: Inborn Error of Immunity-Associated Lymphoproliferative Disorders
- Clinical: Cutaneous involvement in Inborn Error of Immunity-Associated Lymphoproliferative Disorders often presents as generalized papulonodular indurated lesions with variable erythema, scaliness, and a haemorrhagic ulceronecrotic appearance.
- Micro: Microscopically, these lesions show a brisk CD8-positive T-cell–rich infiltrate with a band-like, non-necrotizing confluent granulomatous pattern and minimal to absent lymphoid infiltrate.
- Ancillary: Immunohistochemistry shows the infiltrate to be positive for CD163, CD4, and CD68, and negative for S100, CD1a, and CD207 (langerin); molecular testing excludes EBV and HIV infection.
Reference Gallery:
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. A band-like, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate is observed. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown in <<32513>>); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. CD68 immunohistochemistry reveals a band-like, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown here); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. A cytologically bland, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate is observed. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown in <<32513>>); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is positive for CD163 (<<32516>>) and negative for KIT (CD117) and CD1a (not shown).
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral-predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is positive for CD163 (shown here) and negative for KIT (CD117) and CD1a (not shown).
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral-predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is cytologically bland, and scattered admixed eosinophils are noted. The infiltrate is positive for CD163 (<<32516>>) and negative for KIT (CD117) and CD1a (not shown).
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. A band-like lymphohistiocytic infiltrate is present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. The band-like infiltrate in the upper dermis comprises a mixture of histiocytes and small mature lymphocytes with slightly irregular nuclear contour.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD3 immunohistochemistry highlights a band-like lymphohistiocytic infiltrate present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD4 immunohistochemistry highlights histiocytes and a minority of lymphocytes within the band-like lymphohistiocytic infiltrate present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD8 immunohistochemistry highlights a majority of lymphocytes within the band-like lymphohistiocytic infiltrate present in the upper dermis.
Granulomatous inflammation in RAG2 deficiency. A 33-year-old with history of RAG2 deficiency / combined immunodeficiency with non-healing ulcerating plaques on buttocks for 3 years. Extensive infectious workup was negative. There is central necrosis with granulomatous and mixed dermal inflammation.

Q: Immunohistochemistry of the cutaneous histiocytic infiltrate in Inborn Error of Immunity-Associated Lymphoproliferative Disorders typically demonstrates positivity for macrophage markers (e.g., CD163, CD68) and negativity for Langerhans cell markers such as S100 and [...].
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. CD68 immunohistochemistry reveals a band-like, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown here); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral-predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is positive for CD163 (shown here) and negative for KIT (CD117) and CD1a (not shown).
A: CD1a
Back Extra: Inborn Error of Immunity-Associated Lymphoproliferative Disorders
- Clinical: Cutaneous involvement in Inborn Error of Immunity-Associated Lymphoproliferative Disorders often presents as generalized papulonodular indurated lesions with variable erythema, scaliness, and a haemorrhagic ulceronecrotic appearance.
- Micro: Microscopically, these lesions show a brisk CD8-positive T-cell–rich infiltrate with a band-like, non-necrotizing confluent granulomatous pattern and minimal to absent lymphoid infiltrate.
- Ancillary: Immunohistochemistry shows the infiltrate to be positive for CD163, CD4, and CD68, and negative for S100, CD1a, and CD207 (langerin); molecular testing excludes EBV and HIV infection.
Reference Gallery:
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. A band-like, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate is observed. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown in <<32513>>); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. CD68 immunohistochemistry reveals a band-like, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown here); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. A cytologically bland, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate is observed. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown in <<32513>>); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is positive for CD163 (<<32516>>) and negative for KIT (CD117) and CD1a (not shown).
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral-predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is positive for CD163 (shown here) and negative for KIT (CD117) and CD1a (not shown).
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral-predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is cytologically bland, and scattered admixed eosinophils are noted. The infiltrate is positive for CD163 (<<32516>>) and negative for KIT (CD117) and CD1a (not shown).
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. A band-like lymphohistiocytic infiltrate is present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. The band-like infiltrate in the upper dermis comprises a mixture of histiocytes and small mature lymphocytes with slightly irregular nuclear contour.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD3 immunohistochemistry highlights a band-like lymphohistiocytic infiltrate present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD4 immunohistochemistry highlights histiocytes and a minority of lymphocytes within the band-like lymphohistiocytic infiltrate present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD8 immunohistochemistry highlights a majority of lymphocytes within the band-like lymphohistiocytic infiltrate present in the upper dermis.
Granulomatous inflammation in RAG2 deficiency. A 33-year-old with history of RAG2 deficiency / combined immunodeficiency with non-healing ulcerating plaques on buttocks for 3 years. Extensive infectious workup was negative. There is central necrosis with granulomatous and mixed dermal inflammation.

Q: While characterizing the dermal lymphohistiocytic infiltrate in Inborn Error of Immunity-Associated Lymphoproliferative Disorders, immunohistochemistry typically reveals that the majority of the lymphocytes are [...] T-cells.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD3 immunohistochemistry highlights a band-like lymphohistiocytic infiltrate present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD8 immunohistochemistry highlights a majority of lymphocytes within the band-like lymphohistiocytic infiltrate present in the upper dermis.
A: CD8-positive
Back Extra: Inborn Error of Immunity-Associated Lymphoproliferative Disorders
- Clinical: Cutaneous involvement in Inborn Error of Immunity-Associated Lymphoproliferative Disorders often presents as generalized papulonodular indurated lesions with variable erythema, scaliness, and a haemorrhagic ulceronecrotic appearance.
- Micro: Microscopically, these lesions show a brisk CD8-positive T-cell–rich infiltrate with a band-like, non-necrotizing confluent granulomatous pattern and minimal to absent lymphoid infiltrate.
- Ancillary: Immunohistochemistry shows the infiltrate to be positive for CD163, CD4, and CD68, and negative for S100, CD1a, and CD207 (langerin); molecular testing excludes EBV and HIV infection.
Reference Gallery:
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. A band-like, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate is observed. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown in <<32513>>); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. CD68 immunohistochemistry reveals a band-like, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown here); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. Same patient shown in (<<32515>>, <<32520>>, <<32516>>) at 4 years old, with worsening erythematous papules and red-brown plaques. A cytologically bland, non-necrotizing confluent granulomatous infiltrate with minimal to absent lymphoid infiltrate is observed. The infiltrate is negative for S100, CD1a, and CD207 (langerin); positive for CD163, CD4, and CD68 (CD68 staining shown in <<32513>>); and negative for infectious etiologies after extensive workup.
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is positive for CD163 (<<32516>>) and negative for KIT (CD117) and CD1a (not shown).
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral-predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is positive for CD163 (shown here) and negative for KIT (CD117) and CD1a (not shown).
Histiocyte-predominant presentation of CD8+ T-cell–rich and granulomatous lesion in the setting of common variable immune deficiency. One-year-old infant with recurrent acral-predominant vesicular/pustular eruption and history of common variable immune deficiency. A prominent superficial dermal histiocytic infiltrate is noted, with reactive changes in the overlying epidermis. The infiltrate is cytologically bland, and scattered admixed eosinophils are noted. The infiltrate is positive for CD163 (<<32516>>) and negative for KIT (CD117) and CD1a (not shown).
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. A band-like lymphohistiocytic infiltrate is present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. The band-like infiltrate in the upper dermis comprises a mixture of histiocytes and small mature lymphocytes with slightly irregular nuclear contour.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD3 immunohistochemistry highlights a band-like lymphohistiocytic infiltrate present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD4 immunohistochemistry highlights histiocytes and a minority of lymphocytes within the band-like lymphohistiocytic infiltrate present in the upper dermis.
Dermal lymphohistiocytic infiltrate in the setting of common variable immunodeficiency. A 34-year-old man with common variable immunodeficiency and a 1 year history of progressive rash. CD8 immunohistochemistry highlights a majority of lymphocytes within the band-like lymphohistiocytic infiltrate present in the upper dermis.
Granulomatous inflammation in RAG2 deficiency. A 33-year-old with history of RAG2 deficiency / combined immunodeficiency with non-healing ulcerating plaques on buttocks for 3 years. Extensive infectious workup was negative. There is central necrosis with granulomatous and mixed dermal inflammation.

Q: The underlying molecular defect in Xeroderma Pigmentosum typically involves biallelic mutations in genes responsible for the [...] pathway (e.g., XPA, XPC, ERCC genes).
The nucleotide excision repair (NER) pathway. Transcription-coupled repair (TCR) removes damage from actively transcribed genes, whereas global genome repair (GGR) removes damage from the remainder of the genome {19023283}. Mutations in the genes in rectangles have been associated with clinical disease. PCNA, proliferating cell nuclear antigen; RF-C, replication factor C.
A: nucleotide excision repair
Back Extra: Xeroderma Pigmentosum
- Clinical: Xeroderma pigmentosum (XP) is characterized by acute sunburn following minimal sun exposure, numerous freckle-like hyperpigmented macules on sun-exposed skin, and frequent skin cancers such as basal cell carcinoma, squamous cell carcinoma, and melanoma.
- Micro: Skin and other cancers in XP are morphologically similar to those in the general population, including basal cell carcinoma, squamous cell carcinoma, and melanoma.
- Ancillary: Molecular diagnosis involves identifying biallelic mutations in one of the seven nucleotide excision repair genes (XPA, ERCC3, XPC, ERCC2, DDB2, ERCC4, ERCC5), or the POLH gene.
Reference Gallery:
Xeroderma pigmentosum (XP). A Patient XP420BE, complementation group D, at 9 months of age, with severe blistering erythema of the malar area following minimal sun exposure. Note the sparing of her forehead and eyes, which were protected by a hat. B Patient XP358BE, complementation group C, at 2 years of age, did not sunburn easily but developed multiple hyperpigmented macules on her face. A rapidly growing squamous cell carcinoma or keratoacanthoma grew on her upper lip, and a precancerous lesion appeared on her forehead. C Northern African patient XP393BE, complementation group C, at 23 years of age, with numerous hyperpigmented macules on his face. Nodular basal cell cancer is present on his left nasal root. Pigmented basal cell cancer is present on his left cheek. His eyes show cornea scarring from unprotected sun exposure. D Patient XP19BE, complementation group A, at 35 years of age, with neurological degeneration. He has numerous hyperpigmented macules on sun exposed areas of his face and neck. Progressive sensorineural deafness requires use of a hearing aid.
Skin cancer in the setting of xeroderma pigmentosum. Xeroderma pigmentosum skin cancer by age at first skin cancer diagnosis and skin cancer type compared with the US general population. Upper panel: Proportion of non-melanoma skin cancer (NMSC) patients diagnosed at selected ages. Lower panel: Proportion of melanoma patients diagnosed at selected ages.
The nucleotide excision repair (NER) pathway. Transcription-coupled repair (TCR) removes damage from actively transcribed genes, whereas global genome repair (GGR) removes damage from the remainder of the genome {19023283}. Mutations in the genes in rectangles have been associated with clinical disease. PCNA, proliferating cell nuclear antigen; RF-C, replication factor C.
Xeroderma pigmentosum. Risk factors (odds ratio in red numbers above each bar) for development of internal tumours in xeroderma pigmentosum patients belonging to the French (F), American (A), Brazilian (B), or UK (UK) published xeroderma pigmentosum cohorts as compared with the US general population (gen_pop). Computed from {35246173}.

Q: [...] is a genetic disorder classically characterized by acute sunburn following minimal sun exposure, numerous freckle-like hyperpigmented macules, and frequent early-onset skin cancers (e.g., basal cell carcinoma, squamous cell carcinoma, melanoma).
Xeroderma pigmentosum (XP). A Patient XP420BE, complementation group D, at 9 months of age, with severe blistering erythema of the malar area following minimal sun exposure. Note the sparing of her forehead and eyes, which were protected by a hat. B Patient XP358BE, complementation group C, at 2 years of age, did not sunburn easily but developed multiple hyperpigmented macules on her face. A rapidly growing squamous cell carcinoma or keratoacanthoma grew on her upper lip, and a precancerous lesion appeared on her forehead. C Northern African patient XP393BE, complementation group C, at 23 years of age, with numerous hyperpigmented macules on his face. Nodular basal cell cancer is present on his left nasal root. Pigmented basal cell cancer is present on his left cheek. His eyes show cornea scarring from unprotected sun exposure. D Patient XP19BE, complementation group A, at 35 years of age, with neurological degeneration. He has numerous hyperpigmented macules on sun exposed areas of his face and neck. Progressive sensorineural deafness requires use of a hearing aid.
Skin cancer in the setting of xeroderma pigmentosum. Xeroderma pigmentosum skin cancer by age at first skin cancer diagnosis and skin cancer type compared with the US general population. Upper panel: Proportion of non-melanoma skin cancer (NMSC) patients diagnosed at selected ages. Lower panel: Proportion of melanoma patients diagnosed at selected ages.
A: Xeroderma Pigmentosum
Back Extra: Xeroderma Pigmentosum
- Clinical: Xeroderma pigmentosum (XP) is characterized by acute sunburn following minimal sun exposure, numerous freckle-like hyperpigmented macules on sun-exposed skin, and frequent skin cancers such as basal cell carcinoma, squamous cell carcinoma, and melanoma.
- Micro: Skin and other cancers in XP are morphologically similar to those in the general population, including basal cell carcinoma, squamous cell carcinoma, and melanoma.
- Ancillary: Molecular diagnosis involves identifying biallelic mutations in one of the seven nucleotide excision repair genes (XPA, ERCC3, XPC, ERCC2, DDB2, ERCC4, ERCC5), or the POLH gene.
Reference Gallery:
Xeroderma pigmentosum (XP). A Patient XP420BE, complementation group D, at 9 months of age, with severe blistering erythema of the malar area following minimal sun exposure. Note the sparing of her forehead and eyes, which were protected by a hat. B Patient XP358BE, complementation group C, at 2 years of age, did not sunburn easily but developed multiple hyperpigmented macules on her face. A rapidly growing squamous cell carcinoma or keratoacanthoma grew on her upper lip, and a precancerous lesion appeared on her forehead. C Northern African patient XP393BE, complementation group C, at 23 years of age, with numerous hyperpigmented macules on his face. Nodular basal cell cancer is present on his left nasal root. Pigmented basal cell cancer is present on his left cheek. His eyes show cornea scarring from unprotected sun exposure. D Patient XP19BE, complementation group A, at 35 years of age, with neurological degeneration. He has numerous hyperpigmented macules on sun exposed areas of his face and neck. Progressive sensorineural deafness requires use of a hearing aid.
Skin cancer in the setting of xeroderma pigmentosum. Xeroderma pigmentosum skin cancer by age at first skin cancer diagnosis and skin cancer type compared with the US general population. Upper panel: Proportion of non-melanoma skin cancer (NMSC) patients diagnosed at selected ages. Lower panel: Proportion of melanoma patients diagnosed at selected ages.
The nucleotide excision repair (NER) pathway. Transcription-coupled repair (TCR) removes damage from actively transcribed genes, whereas global genome repair (GGR) removes damage from the remainder of the genome {19023283}. Mutations in the genes in rectangles have been associated with clinical disease. PCNA, proliferating cell nuclear antigen; RF-C, replication factor C.
Xeroderma pigmentosum. Risk factors (odds ratio in red numbers above each bar) for development of internal tumours in xeroderma pigmentosum patients belonging to the French (F), American (A), Brazilian (B), or UK (UK) published xeroderma pigmentosum cohorts as compared with the US general population (gen_pop). Computed from {35246173}.

Q: A rapidly growing, well-circumscribed subcuticular mass that microscopically shows features of nodular fasciitis admixed with bone formation is characteristic of [...].
Fibro-osseous pseudotumour of digits. The lesion presents as a well-circumscribed subcuticular mass.
A: fibro-osseous tumor of digits
Back Extra: Fibro-osseous tumour of digits
- Clinical: Fibro-osseous tumour of digits is a rapidly growing, often painful lesion that can present with random calcifications on imaging studies and a broad age distribution, commonly affecting young adults.
- Micro: The lesion shows areas resembling nodular fasciitis with bone in various stages of formation, hypercellularity, and spindle cells with eosinophilic cytoplasm and plump fusiform nuclei.
- Ancillary: USP6 fusion genes are present in fibro-osseous tumour of digits, similar to nodular fasciitis, and molecular studies for USP6 rearrangement can be useful in diagnosis.
Reference Gallery:
Fibro-osseous pseudotumour of digits. The lesion presents as a well-circumscribed subcuticular mass.

Q: Similar to nodular fasciitis, the spindle cells in a fibro-osseous tumor of digits frequently harbor diagnostic fusions involving the [...] gene.
Fibro-osseous pseudotumour of digits. The lesion presents as a well-circumscribed subcuticular mass.
A: USP6
Back Extra: Fibro-osseous tumour of digits
- Clinical: Fibro-osseous tumour of digits is a rapidly growing, often painful lesion that can present with random calcifications on imaging studies and a broad age distribution, commonly affecting young adults.
- Micro: The lesion shows areas resembling nodular fasciitis with bone in various stages of formation, hypercellularity, and spindle cells with eosinophilic cytoplasm and plump fusiform nuclei.
- Ancillary: USP6 fusion genes are present in fibro-osseous tumour of digits, similar to nodular fasciitis, and molecular studies for USP6 rearrangement can be useful in diagnosis.
Reference Gallery:
Fibro-osseous pseudotumour of digits. The lesion presents as a well-circumscribed subcuticular mass.

Q: A primary tumor of the vulva that is histologically identical to breast carcinoma, often exhibiting features like stromal elastosis and tubulolobular growth (as seen in the provided histology), is diagnosed as [...].
Adenocarcinoma of the mammary-like glands of the vulva. Mammary-type tubulolobular carcinoma with areas of both tubular formation and a single-file pattern, resembling an invasive lobular carcinoma. Note the stromal and periductal elastosis.
A: Adenocarcinoma of mammary gland type
Back Extra: Adenocarcinoma of mammary gland type
- Clinical: Adenocarcinoma of mammary gland type most commonly presents as a vulval mass in postmenopausal women, with the labia majora being the most frequent location.
- Micro: Histologically, it is identical to mammary invasive ductal carcinoma, with common expression of ER, PR, GATA3, and ERBB2, and can be classified into subtypes like luminal A, luminal B, HER2-enriched, and basal-like.
- Ancillary: Immunohistochemistry often shows positivity for ER, PR, GATA3, and ERBB2, and molecular studies may reveal mutations in the PI3K/AKT cascade or the characteristic ETV6::NTRK3 fusion in secretory carcinoma.
Reference Gallery:
Adenocarcinoma of the mammary-like glands of the vulva. Mammary-type tubulolobular carcinoma with areas of both tubular formation and a single-file pattern, resembling an invasive lobular carcinoma. Note the stromal and periductal elastosis.

Q: When Adenocarcinoma of mammary gland type of the vulva presents as a tubulolobular variant, it closely mimics invasive lobular carcinoma of the breast by displaying cells arranged in a characteristic [...] pattern.
Adenocarcinoma of the mammary-like glands of the vulva. Mammary-type tubulolobular carcinoma with areas of both tubular formation and a single-file pattern, resembling an invasive lobular carcinoma. Note the stromal and periductal elastosis.
A: single-file
Back Extra: Adenocarcinoma of mammary gland type
- Clinical: Adenocarcinoma of mammary gland type most commonly presents as a vulval mass in postmenopausal women, with the labia majora being the most frequent location.
- Micro: Histologically, it is identical to mammary invasive ductal carcinoma, with common expression of ER, PR, GATA3, and ERBB2, and can be classified into subtypes like luminal A, luminal B, HER2-enriched, and basal-like.
- Ancillary: Immunohistochemistry often shows positivity for ER, PR, GATA3, and ERBB2, and molecular studies may reveal mutations in the PI3K/AKT cascade or the characteristic ETV6::NTRK3 fusion in secretory carcinoma.
Reference Gallery:
Adenocarcinoma of the mammary-like glands of the vulva. Mammary-type tubulolobular carcinoma with areas of both tubular formation and a single-file pattern, resembling an invasive lobular carcinoma. Note the stromal and periductal elastosis.

Q: Apocrine carcinoma may feature an in situ component characterized by atypical glands that remain surrounded by an intact [...] cell layer (often highlighted by α-SMA).
Apocrine carcinoma. In situ component in apocrine carcinoma. Staining for α-SMA reveals a myoepithelial cell layer around atypical glands.
A: myoepithelial
Back Extra: Apocrine Carcinoma
- Clinical: Apocrine carcinoma presents as a solitary nodule or multinodular mass, often ≥ 20 mm, and may be ulcerated or hemorrhagic. It typically affects adults in their fifth or sixth decade of life.
- Micro: The neoplasm shows papillary, tubular, and solid growth patterns with eosinophilic cytoplasm and variable nuclear pleomorphism. An in situ component may also be present.
- Ancillary: Immunohistochemistry shows expression of cytokeratins (including CK7), GCDFP-15, and variable positivity for CEA, S100, EMA, ER, PR, and AR.
Reference Gallery:
Apocrine carcinoma. Part of this tumour constitutes ductal carcinoma in situ; it has a cribriform appearance, with atypical epithelial cells showing abnormal mitotic figures and intact peripheral basal/myoepithelial cells. Focal apocrine secretion is evident.
Apocrine carcinoma. Part of this tumour constitutes ductal carcinoma in situ; it has a cribriform appearance, with atypical epithelial cells showing abnormal mitotic figures (arrows) and intact peripheral basal/myoepithelial cells. Focal apocrine secretion is evident.
Apocrine carcinoma. In situ component in apocrine carcinoma. Staining for α-SMA reveals a myoepithelial cell layer around atypical glands.
Apocrine carcinoma NOS. Clinical appearance of a lesion in the axillary skin, raising the differential diagnosis with breast cancer.

Q: Cutaneous apocrine carcinoma frequently presents as a nodular mass in areas rich in apocrine glands, such as the [...], raising a clinical differential diagnosis of metastatic breast cancer.
Apocrine carcinoma NOS. Clinical appearance of a lesion in the axillary skin, raising the differential diagnosis with breast cancer.
A: axilla
Back Extra: Apocrine Carcinoma
- Clinical: Apocrine carcinoma presents as a solitary nodule or multinodular mass, often ≥ 20 mm, and may be ulcerated or hemorrhagic. It typically affects adults in their fifth or sixth decade of life.
- Micro: The neoplasm shows papillary, tubular, and solid growth patterns with eosinophilic cytoplasm and variable nuclear pleomorphism. An in situ component may also be present.
- Ancillary: Immunohistochemistry shows expression of cytokeratins (including CK7), GCDFP-15, and variable positivity for CEA, S100, EMA, ER, PR, and AR.
Reference Gallery:
Apocrine carcinoma. Part of this tumour constitutes ductal carcinoma in situ; it has a cribriform appearance, with atypical epithelial cells showing abnormal mitotic figures and intact peripheral basal/myoepithelial cells. Focal apocrine secretion is evident.
Apocrine carcinoma. Part of this tumour constitutes ductal carcinoma in situ; it has a cribriform appearance, with atypical epithelial cells showing abnormal mitotic figures (arrows) and intact peripheral basal/myoepithelial cells. Focal apocrine secretion is evident.
Apocrine carcinoma. In situ component in apocrine carcinoma. Staining for α-SMA reveals a myoepithelial cell layer around atypical glands.
Apocrine carcinoma NOS. Clinical appearance of a lesion in the axillary skin, raising the differential diagnosis with breast cancer.

Q: Apocrine carcinoma often demonstrates an in situ component with a cribriform pattern, atypical cells with abnormal mitoses, and focal [...] secretion.
Apocrine carcinoma. Part of this tumour constitutes ductal carcinoma in situ; it has a cribriform appearance, with atypical epithelial cells showing abnormal mitotic figures and intact peripheral basal/myoepithelial cells. Focal apocrine secretion is evident.
Apocrine carcinoma. Part of this tumour constitutes ductal carcinoma in situ; it has a cribriform appearance, with atypical epithelial cells showing abnormal mitotic figures (arrows) and intact peripheral basal/myoepithelial cells. Focal apocrine secretion is evident.
A: apocrine
Back Extra: Apocrine Carcinoma
- Clinical: Apocrine carcinoma presents as a solitary nodule or multinodular mass, often ≥ 20 mm, and may be ulcerated or hemorrhagic. It typically affects adults in their fifth or sixth decade of life.
- Micro: The neoplasm shows papillary, tubular, and solid growth patterns with eosinophilic cytoplasm and variable nuclear pleomorphism. An in situ component may also be present.
- Ancillary: Immunohistochemistry shows expression of cytokeratins (including CK7), GCDFP-15, and variable positivity for CEA, S100, EMA, ER, PR, and AR.
Reference Gallery:
Apocrine carcinoma. Part of this tumour constitutes ductal carcinoma in situ; it has a cribriform appearance, with atypical epithelial cells showing abnormal mitotic figures and intact peripheral basal/myoepithelial cells. Focal apocrine secretion is evident.
Apocrine carcinoma. Part of this tumour constitutes ductal carcinoma in situ; it has a cribriform appearance, with atypical epithelial cells showing abnormal mitotic figures (arrows) and intact peripheral basal/myoepithelial cells. Focal apocrine secretion is evident.
Apocrine carcinoma. In situ component in apocrine carcinoma. Staining for α-SMA reveals a myoepithelial cell layer around atypical glands.
Apocrine carcinoma NOS. Clinical appearance of a lesion in the axillary skin, raising the differential diagnosis with breast cancer.

Q: Histologically, [...] features interconnected solid nests and characteristic sieve-like architectures with thin, thread-like intraluminal bridges set within a desmoplastic stroma.
Cribriform tumour. An example with pronounced cribriform architecture. Note the lymphoid aggregates at the periphery of the neoplasm and the layer of compressed fibrous tissue.
Cribriform tumour. Neoplastic epithelial cells with eosinophilic cytoplasm and pleomorphic and hyperchromatic nuclei in a desmoplastic stroma. Note the thin thread-like intraluminal bridges.
A: cribriform tumor
Back Extra: Cribriform Tumour
- Clinical: Cribriform tumour typically presents as a solitary, skin-coloured nodule on the lower extremities, often firm on palpation and with a duration ranging from several months to years.
- Micro: Cribriform tumour is characterized by interconnected solid nests and cribriform structures of epithelial cells with eosinophilic cytoplasm and hyperchromatic nuclei, often with intraluminal micropapillary projections and thin intraluminal bridges.
- Ancillary: Immunohistochemistry shows positivity for cytokeratins (MNF116, AE1/AE3, CAM5.2, CK5/6, CK7) and BerEP4, but negativity for GATA3, S100, CD15, CD31, and PR.
Reference Gallery:
Cribriform tumour. Neoplastic epithelial cells with eosinophilic cytoplasm and pleomorphic and hyperchromatic nuclei in a desmoplastic stroma.
Cribriform tumour. An example with pronounced cribriform architecture. Note the lymphoid aggregates at the periphery of the neoplasm and the layer of compressed fibrous tissue.
Cribriform tumour. Neoplastic epithelial cells with eosinophilic cytoplasm and pleomorphic and hyperchromatic nuclei in a desmoplastic stroma. Note the thin thread-like intraluminal bridges.
Cribriform tumour. Comparison of H&E and GATA3 staining. Panoramic and detail of a primary cutaneous apocrine cribriform carcinoma with H&E (<<37368>>) and GATA3-negative staining of the same tumour (<<37369>>).
Cribriform tumour. Comparison of H&E and GATA3 staining. Panoramic and detail of a primary cutaneous apocrine cribriform carcinoma with H&E (<<37368>>) and GATA3-negative staining of the same tumour (<<37369>>).
Cribriform tumour. High-power view of cribriform structures of a primary cutaneous apocrine cribriform carcinoma.
Cribriform tumour. GATA3 immunohistochemistry is negative (H&E <<37370>>).

Q: In primary cutaneous cribriform tumor, immunohistochemistry is notably negative for [...], which is a critical finding to help distinguish it from metastatic breast carcinoma.
Cribriform tumour. Comparison of H&E and GATA3 staining. Panoramic and detail of a primary cutaneous apocrine cribriform carcinoma with H&E (<<37368>>) and GATA3-negative staining of the same tumour (<<37369>>).
Cribriform tumour. GATA3 immunohistochemistry is negative (H&E <<37370>>).
A: GATA3
Back Extra: Cribriform Tumour
- Clinical: Cribriform tumour typically presents as a solitary, skin-coloured nodule on the lower extremities, often firm on palpation and with a duration ranging from several months to years.
- Micro: Cribriform tumour is characterized by interconnected solid nests and cribriform structures of epithelial cells with eosinophilic cytoplasm and hyperchromatic nuclei, often with intraluminal micropapillary projections and thin intraluminal bridges.
- Ancillary: Immunohistochemistry shows positivity for cytokeratins (MNF116, AE1/AE3, CAM5.2, CK5/6, CK7) and BerEP4, but negativity for GATA3, S100, CD15, CD31, and PR.
Reference Gallery:
Cribriform tumour. Neoplastic epithelial cells with eosinophilic cytoplasm and pleomorphic and hyperchromatic nuclei in a desmoplastic stroma.
Cribriform tumour. An example with pronounced cribriform architecture. Note the lymphoid aggregates at the periphery of the neoplasm and the layer of compressed fibrous tissue.
Cribriform tumour. Neoplastic epithelial cells with eosinophilic cytoplasm and pleomorphic and hyperchromatic nuclei in a desmoplastic stroma. Note the thin thread-like intraluminal bridges.
Cribriform tumour. Comparison of H&E and GATA3 staining. Panoramic and detail of a primary cutaneous apocrine cribriform carcinoma with H&E (<<37368>>) and GATA3-negative staining of the same tumour (<<37369>>).
Cribriform tumour. Comparison of H&E and GATA3 staining. Panoramic and detail of a primary cutaneous apocrine cribriform carcinoma with H&E (<<37368>>) and GATA3-negative staining of the same tumour (<<37369>>).
Cribriform tumour. High-power view of cribriform structures of a primary cutaneous apocrine cribriform carcinoma.
Cribriform tumour. GATA3 immunohistochemistry is negative (H&E <<37370>>).

Q: A biphasic neoplasm of the vulva or perianal region displaying elongated, anastomosing glands with a pericanalicular growth pattern and a paucicellular stroma is characteristic of the fibroadenoma variant of [...].
Fibroadenoma of anogenital mammary-like glands. The biphasic neoplasm is composed of elongated, branching, and anastomosing glandular structures surrounded by paucicellular stroma; the glandular lumina maintain round to oval configurations (a pericanalicular growth pattern).
Fibroadenoma of anogenital mammary-like glands. The biphasic neoplasm is composed of elongated, branching, and anastomosing glandular structures surrounded by paucicellular stroma; the glandular lumina maintain round to oval configurations (a pericanalicular growth pattern).
A: Fibroadenoma and Phyllodes Tumor of Anogenital Mammary-like Glands
Back Extra: Fibroadenoma and Phyllodes Tumour of Anogenital Mammary-like Glands
- Clinical: Fibroadenoma and Phyllodes Tumour of Anogenital Mammary-like Glands occur as solitary nodules measuring 8–60 mm, typically found in the vulva and perianal area, with most cases reported in females aged 20-69 years.
- Micro: Fibroadenoma is characterized by a well-circumscribed neoplasm with elongated, branching glandular structures and paucicellular stroma, while Phyllodes Tumour shows leaf-like projections and stromal hypercellularity.
- Ancillary: The epithelial component stains for ER, PR, and GATA3, and mutations in AKT1 and MET are identified in fibroadenoma, while low-grade phyllodes tumours may have ABL1 and TP53 mutations.
Reference Gallery:
Fibroadenoma of anogenital mammary-like glands. The biphasic neoplasm is composed of elongated, branching, and anastomosing glandular structures surrounded by paucicellular stroma; the glandular lumina maintain round to oval configurations (a pericanalicular growth pattern).
Fibroadenoma of anogenital mammary-like glands. The biphasic neoplasm is composed of elongated, branching, and anastomosing glandular structures surrounded by paucicellular stroma; the glandular lumina maintain round to oval configurations (a pericanalicular growth pattern).
Phyllodes tumour of anogenital mammary-like glands. Benign tumour with a leaf-like growth pattern and stromal hypercellularity.
Phyllodes tumour of anogenital mammary-like glands. Note the classic periglandular condensation of the stroma.

Q: Within the spectrum of Fibroadenoma and Phyllodes Tumor of Anogenital Mammary-like Glands, the phyllodes variant is morphologically distinguished by stromal hypercellularity, periglandular stromal condensation, and a characteristic [...] growth pattern.
Phyllodes tumour of anogenital mammary-like glands. Benign tumour with a leaf-like growth pattern and stromal hypercellularity.
Phyllodes tumour of anogenital mammary-like glands. Note the classic periglandular condensation of the stroma.
A: leaf-like
Back Extra: Fibroadenoma and Phyllodes Tumour of Anogenital Mammary-like Glands
- Clinical: Fibroadenoma and Phyllodes Tumour of Anogenital Mammary-like Glands occur as solitary nodules measuring 8–60 mm, typically found in the vulva and perianal area, with most cases reported in females aged 20-69 years.
- Micro: Fibroadenoma is characterized by a well-circumscribed neoplasm with elongated, branching glandular structures and paucicellular stroma, while Phyllodes Tumour shows leaf-like projections and stromal hypercellularity.
- Ancillary: The epithelial component stains for ER, PR, and GATA3, and mutations in AKT1 and MET are identified in fibroadenoma, while low-grade phyllodes tumours may have ABL1 and TP53 mutations.
Reference Gallery:
Fibroadenoma of anogenital mammary-like glands. The biphasic neoplasm is composed of elongated, branching, and anastomosing glandular structures surrounded by paucicellular stroma; the glandular lumina maintain round to oval configurations (a pericanalicular growth pattern).
Fibroadenoma of anogenital mammary-like glands. The biphasic neoplasm is composed of elongated, branching, and anastomosing glandular structures surrounded by paucicellular stroma; the glandular lumina maintain round to oval configurations (a pericanalicular growth pattern).
Phyllodes tumour of anogenital mammary-like glands. Benign tumour with a leaf-like growth pattern and stromal hypercellularity.
Phyllodes tumour of anogenital mammary-like glands. Note the classic periglandular condensation of the stroma.

Q: Hidradenoma papilliferum is a benign adnexal neoplasm that classically presents as a solitary, asymptomatic nodule or cyst-like lesion most commonly located on the [...].
Hidradenoma papilliferum. Clinical appearance of a vulvar lesion in a 52-year-old female patient.
A: vulva
Back Extra: Hidradenoma papilliferum
- Clinical: Hidradenoma papilliferum is a benign neoplasm that typically presents as a solitary, asymptomatic nodule or cyst-like lesion, most commonly in the vulva of White women aged 20-89 years.
- Micro: Microscopically, hidradenoma papilliferum shows a well-circumscribed, intradermal solid-cystic nodule with branching and anastomosing tubules, often forming papillae. The tubules are lined by a double layer of cells, with decapitation secretion being a common finding.
- Ancillary: No specific ancillary studies are typically required for the diagnosis of hidradenoma papilliferum.
Reference Gallery:
Hidradenoma papilliferum. Well-circumscribed cystic neoplasm with prominent papillary projections.
Hidradenoma papilliferum. The double epithelial lining consists of a peripheral layer of cuboidal myoepithelial cells and a luminal layer of columnar cells, many of which exhibit decapitation secretion.
Hidradenoma papilliferum. Clinical appearance of a vulvar lesion in a 52-year-old female patient.

Q: Microscopically, hidradenoma papilliferum features a well-circumscribed solid-cystic nodule with complex branching papillae lined by a double layer of cells that frequently exhibit [...].
Hidradenoma papilliferum. Well-circumscribed cystic neoplasm with prominent papillary projections.
Hidradenoma papilliferum. The double epithelial lining consists of a peripheral layer of cuboidal myoepithelial cells and a luminal layer of columnar cells, many of which exhibit decapitation secretion.
A: decapitation secretion
Back Extra: Hidradenoma papilliferum
- Clinical: Hidradenoma papilliferum is a benign neoplasm that typically presents as a solitary, asymptomatic nodule or cyst-like lesion, most commonly in the vulva of White women aged 20-89 years.
- Micro: Microscopically, hidradenoma papilliferum shows a well-circumscribed, intradermal solid-cystic nodule with branching and anastomosing tubules, often forming papillae. The tubules are lined by a double layer of cells, with decapitation secretion being a common finding.
- Ancillary: No specific ancillary studies are typically required for the diagnosis of hidradenoma papilliferum.
Reference Gallery:
Hidradenoma papilliferum. Well-circumscribed cystic neoplasm with prominent papillary projections.
Hidradenoma papilliferum. The double epithelial lining consists of a peripheral layer of cuboidal myoepithelial cells and a luminal layer of columnar cells, many of which exhibit decapitation secretion.
Hidradenoma papilliferum. Clinical appearance of a vulvar lesion in a 52-year-old female patient.

Q: A malignant adnexal tumor exhibiting a papillary architecture with nuclear atypia, abnormal mitoses, and frequently arising within a sebaceous nevus is [...].
Syringocystadenocarcinoma papilliferum. The tumour shows a papillary architecture.
Syringocystadenocarcinoma papilliferum. There are areas exhibiting nuclear and cellular atypia, abnormal mitotic figures (arrows), loss of polarity, and a focal disorderly proliferation of the neoplastic cells. The atypical epithelium is delineated from the adjacent dermis by an intact basal/myoepithelial cell layer, qualifying this tumour as syringocystadenocarcinoma papilliferum in situ.
A: Syringocystadenocarcinoma papilliferum
Back Extra: Syringocystadenocarcinoma papilliferum
- Clinical: Syringocystadenocarcinoma papilliferum appears as a nodule, inflammatory plaque, or tumour, sometimes ulcerated, and is often associated with a sebaceous naevus.
- Micro: The tumour shows papillary architecture with areas of nuclear and cellular atypia, abnormal mitotic figures, and loss of polarity.
- Ancillary: Myoepithelial cell markers can highlight the in situ component, and CK7 and CAM5.2 are positive in the epithelial cells.
Reference Gallery:
Syringocystadenocarcinoma papilliferum. The tumour shows a papillary architecture.
Syringocystadenocarcinoma papilliferum. There are areas exhibiting nuclear and cellular atypia, abnormal mitotic figures (arrows), loss of polarity, and a focal disorderly proliferation of the neoplastic cells. The atypical epithelium is delineated from the adjacent dermis by an intact basal/myoepithelial cell layer, qualifying this tumour as syringocystadenocarcinoma papilliferum in situ.

Q: In the in situ phase of Syringocystadenocarcinoma papilliferum, the atypical epithelium with loss of polarity is delineated from the adjacent dermis by an intact layer of [...] cells.
Syringocystadenocarcinoma papilliferum. There are areas exhibiting nuclear and cellular atypia, abnormal mitotic figures (arrows), loss of polarity, and a focal disorderly proliferation of the neoplastic cells. The atypical epithelium is delineated from the adjacent dermis by an intact basal/myoepithelial cell layer, qualifying this tumour as syringocystadenocarcinoma papilliferum in situ.
A: myoepithelial
Back Extra: Syringocystadenocarcinoma papilliferum
- Clinical: Syringocystadenocarcinoma papilliferum appears as a nodule, inflammatory plaque, or tumour, sometimes ulcerated, and is often associated with a sebaceous naevus.
- Micro: The tumour shows papillary architecture with areas of nuclear and cellular atypia, abnormal mitotic figures, and loss of polarity.
- Ancillary: Myoepithelial cell markers can highlight the in situ component, and CK7 and CAM5.2 are positive in the epithelial cells.
Reference Gallery:
Syringocystadenocarcinoma papilliferum. The tumour shows a papillary architecture.
Syringocystadenocarcinoma papilliferum. There are areas exhibiting nuclear and cellular atypia, abnormal mitotic figures (arrows), loss of polarity, and a focal disorderly proliferation of the neoplastic cells. The atypical epithelium is delineated from the adjacent dermis by an intact basal/myoepithelial cell layer, qualifying this tumour as syringocystadenocarcinoma papilliferum in situ.

Q: Histologically, the fibrovascular cores and stroma of Syringocystadenoma papilliferum characteristically contain a dense inflammatory infiltrate predominantly composed of [...].
Syringocystadenoma papilliferum. The tumour consists of tubular structures lined by two or more layers of cuboidal epithelium. The stroma shows an associated inflammatory infiltrate.
Syringocystadenoma papilliferum. Detail of the lining and inflammatory infiltrate composed of numerous plasma cells.
A: plasma cells
Back Extra: Syringocystadenoma papilliferum
- Clinical: Syringocystadenoma papilliferum presents as a solitary papule or nodule, often associated with naevus sebaceus of Jadassohn, and has a female predilection.
- Micro: The lesion is characterized by dilated papillary and cystic structures lined by two layers of cells, with the luminal cells showing decapitation secretion and the outer layer being myoepithelial.
- Ancillary: BRAF p.V600E and HRAS mutations are commonly associated with syringocystadenoma papilliferum, and the luminal cells are positive for CEA and EMA, while the outer layer is reactive for myoepithelial markers.
Reference Gallery:
Syringocystadenoma papilliferum. A broad and ulcerated papillary neoplasm on the skin surface.
Syringocystadenoma papilliferum. The tumour consists of tubular structures lined by two or more layers of cuboidal epithelium. The stroma shows an associated inflammatory infiltrate.
Syringocystadenoma papilliferum. Detail of the lining and inflammatory infiltrate composed of numerous plasma cells.

Q: The papillary and cystic structures of Syringocystadenoma papilliferum are lined by two cell layers, with the luminal layer classically demonstrating [...] secretion.
Syringocystadenoma papilliferum. The tumour consists of tubular structures lined by two or more layers of cuboidal epithelium. The stroma shows an associated inflammatory infiltrate.
A: decapitation
Back Extra: Syringocystadenoma papilliferum
- Clinical: Syringocystadenoma papilliferum presents as a solitary papule or nodule, often associated with naevus sebaceus of Jadassohn, and has a female predilection.
- Micro: The lesion is characterized by dilated papillary and cystic structures lined by two layers of cells, with the luminal cells showing decapitation secretion and the outer layer being myoepithelial.
- Ancillary: BRAF p.V600E and HRAS mutations are commonly associated with syringocystadenoma papilliferum, and the luminal cells are positive for CEA and EMA, while the outer layer is reactive for myoepithelial markers.
Reference Gallery:
Syringocystadenoma papilliferum. A broad and ulcerated papillary neoplasm on the skin surface.
Syringocystadenoma papilliferum. The tumour consists of tubular structures lined by two or more layers of cuboidal epithelium. The stroma shows an associated inflammatory infiltrate.
Syringocystadenoma papilliferum. Detail of the lining and inflammatory infiltrate composed of numerous plasma cells.

Q: Microscopically, [...] is characterized by a well-circumscribed dermal neoplasm composed of numerous tubular and ductal structures that frequently contain internal papillary projections.
Tubular papillary adenoma. A well-circumscribed neoplasm composed of numerous tubular and ductal structures.
Tubular papillary adenoma. There are papillary projections inside the tubules, with necrosis and calcification.
A: Tubular Adenoma
Back Extra: Tubular Adenoma
- Clinical: Tubular adenomas appear as asymptomatic, single, well-circumscribed nodules, most commonly on the lower limbs in middle-aged women.
- Micro: The lesions show well-circumscribed dermal neoplasms with a lobular architecture, containing multiple tubular structures lined by cuboidal to flattened cells and columnar cells with papillary projections.
- Ancillary: Immunohistochemistry shows luminal cells positive for CEA and EMA, and outer cells positive for myoepithelial markers like SMA, calponin, SOX10, and p63.
Reference Gallery:
Tubular papillary adenoma. A well-circumscribed neoplasm composed of numerous tubular and ductal structures.
Tubular papillary adenoma. There are papillary projections inside the tubules, with necrosis and calcification.

Q: In Tubular Adenoma, the prominent tubular structures are lined by cuboidal to columnar cells that frequently form internal [...], which may be accompanied by necrosis and calcification.
Tubular papillary adenoma. There are papillary projections inside the tubules, with necrosis and calcification.
A: papillary projections
Back Extra: Tubular Adenoma
- Clinical: Tubular adenomas appear as asymptomatic, single, well-circumscribed nodules, most commonly on the lower limbs in middle-aged women.
- Micro: The lesions show well-circumscribed dermal neoplasms with a lobular architecture, containing multiple tubular structures lined by cuboidal to flattened cells and columnar cells with papillary projections.
- Ancillary: Immunohistochemistry shows luminal cells positive for CEA and EMA, and outer cells positive for myoepithelial markers like SMA, calponin, SOX10, and p63.
Reference Gallery:
Tubular papillary adenoma. A well-circumscribed neoplasm composed of numerous tubular and ductal structures.
Tubular papillary adenoma. There are papillary projections inside the tubules, with necrosis and calcification.

Q: Histologically, Adnexal Adenocarcinoma NOS is characterized by an asymmetrical, poorly circumscribed infiltrative growth pattern forming atypical [...] structures, which frequently invade deep tissues such as skeletal muscle.
Adnexal adenocarcinoma. Deep invasion involving skeletal muscle.
Adnexal adenocarcinoma. Ducts and glands with high-grade atypia, infiltrating among skeletal muscle fibres.
A: ductal and glandular
Back Extra: Adnexal Adenocarcinoma NOS
- Clinical: Adnexal Adenocarcinoma NOS typically presents as a solitary nodule or plaque in the elderly, often on the head and neck.
- Micro: Histologically, the tumor is characterized by asymmetrical, poorly circumscribed, and infiltrative growth patterns with ductal/glandular structures and pleomorphic nuclei.
- Ancillary: Immunohistochemistry shows positivity for EMA, CEA, and focal expression of p63 and p40.
Reference Gallery:
Adnexal adenocarcinoma. Low-power view of a large, deeply invasive lesion involving most of the eyelid.
Adnexal adenocarcinoma. Deep invasion involving skeletal muscle.
Adnexal adenocarcinoma. Ducts and glands with high-grade atypia, infiltrating among skeletal muscle fibres.

Q: An asymmetrical, deeply infiltrative head and neck tumor in an elderly patient, showing high-grade ductal and glandular structures with pleomorphic nuclei invading skeletal muscle, is highly characteristic of [...].
Adnexal adenocarcinoma. Low-power view of a large, deeply invasive lesion involving most of the eyelid.
Adnexal adenocarcinoma. Ducts and glands with high-grade atypia, infiltrating among skeletal muscle fibres.
A: Adnexal Adenocarcinoma NOS
Back Extra: Adnexal Adenocarcinoma NOS
- Clinical: Adnexal Adenocarcinoma NOS typically presents as a solitary nodule or plaque in the elderly, often on the head and neck.
- Micro: Histologically, the tumor is characterized by asymmetrical, poorly circumscribed, and infiltrative growth patterns with ductal/glandular structures and pleomorphic nuclei.
- Ancillary: Immunohistochemistry shows positivity for EMA, CEA, and focal expression of p63 and p40.
Reference Gallery:
Adnexal adenocarcinoma. Low-power view of a large, deeply invasive lesion involving most of the eyelid.
Adnexal adenocarcinoma. Deep invasion involving skeletal muscle.
Adnexal adenocarcinoma. Ducts and glands with high-grade atypia, infiltrating among skeletal muscle fibres.

Q: A biphasic skin tumor showing superficial squamous differentiation and deeper ductal differentiation within a desmoplastic stroma is characteristic of [...].
Squamoid eccrine ductal carcinoma. There are deeper strands of atypical cells with clear ductal formation and desmoplastic stroma in this example.
Squamoid eccrine ductal carcinoma. Biphasic infiltrative dermal and subcutaneous tumour with a superficial component with features of a squamous cell carcinoma and a deeper component with ductal differentiation. A desmoplastic stroma is also seen.
A: Squamoid eccrine ductal carcinoma
Back Extra: Squamoid eccrine ductal carcinoma
- Clinical: Squamoid eccrine ductal carcinoma presents as large nodules and plaques, often in sun-damaged skin of elderly White individuals with a male predominance.
- Micro: The tumour has a biphasic appearance with superficial squamous differentiation and deeper ductal differentiation in a desmoplastic stroma.
- Ancillary: UV radiation signature mutations, including TP53 and NOTCH mutations, are commonly found in squamoid eccrine ductal carcinoma.
Reference Gallery:
Squamoid eccrine ductal carcinoma. There are deeper strands of atypical cells with clear ductal formation and desmoplastic stroma in this example.
Squamoid eccrine ductal carcinoma. CEA highlights ductal structures within the tumour.
Squamoid eccrine ductal carcinoma. Biphasic infiltrative dermal and subcutaneous tumour with a superficial component with features of a squamous cell carcinoma and a deeper component with ductal differentiation. A desmoplastic stroma is also seen.

Q: In Squamoid eccrine ductal carcinoma, the deeper ductal structures within the tumor can be highlighted by immunohistochemistry for [...].
Squamoid eccrine ductal carcinoma. CEA highlights ductal structures within the tumour.
A: CEA
Back Extra: Squamoid eccrine ductal carcinoma
- Clinical: Squamoid eccrine ductal carcinoma presents as large nodules and plaques, often in sun-damaged skin of elderly White individuals with a male predominance.
- Micro: The tumour has a biphasic appearance with superficial squamous differentiation and deeper ductal differentiation in a desmoplastic stroma.
- Ancillary: UV radiation signature mutations, including TP53 and NOTCH mutations, are commonly found in squamoid eccrine ductal carcinoma.
Reference Gallery:
Squamoid eccrine ductal carcinoma. There are deeper strands of atypical cells with clear ductal formation and desmoplastic stroma in this example.
Squamoid eccrine ductal carcinoma. CEA highlights ductal structures within the tumour.
Squamoid eccrine ductal carcinoma. Biphasic infiltrative dermal and subcutaneous tumour with a superficial component with features of a squamous cell carcinoma and a deeper component with ductal differentiation. A desmoplastic stroma is also seen.

Q: The essential diagnostic feature of Adenoid Cystic Carcinoma is the microscopic coexistence of true small bilayered ducts and [...].
Adenoid cystic carcinoma. The essential diagnostic feature is the coexistence of true small bilayered ducts and pseudocysts.
A: pseudocysts
Back Extra: Adenoid Cystic Carcinoma
- Clinical: Adenoid cystic carcinoma (AdCC) typically presents as a solitary nodule, often present for several years, and is more common in middle-aged to elderly individuals with a slight female predilection.
- Micro: Key microscopic features include a mixture of cribriform, tubular, and solid patterns, with true small bilayered ducts and pseudocysts, and frequent perineural invasion.
- Ancillary: Immunohistochemistry shows diffuse positivity for broad-spectrum keratins, CAM5.2, and CK7, with nuclear staining for SOX10 in basaloid and myoepithelial cells.
Reference Gallery:
Adenoid cystic carcinoma. Cribriform, tubular, and solid patterns are typical of this neoplasm, as is perineural or intraneural invasion.
Adenoid cystic carcinoma. Perineural and intraneural invasion.
Adenoid cystic carcinoma. The essential diagnostic feature is the coexistence of true small bilayered ducts and pseudocysts.
Adenoid cystic carcinoma. Areas with myoepithelial differentiation stain positively for α-SMA.

Q: A highly characteristic histologic feature of Adenoid Cystic Carcinoma, often seen alongside its typical cribriform and tubular patterns, is prominent [...] invasion.
Adenoid cystic carcinoma. Cribriform, tubular, and solid patterns are typical of this neoplasm, as is perineural or intraneural invasion.
Adenoid cystic carcinoma. Perineural and intraneural invasion.
A: perineural
Back Extra: Adenoid Cystic Carcinoma
- Clinical: Adenoid cystic carcinoma (AdCC) typically presents as a solitary nodule, often present for several years, and is more common in middle-aged to elderly individuals with a slight female predilection.
- Micro: Key microscopic features include a mixture of cribriform, tubular, and solid patterns, with true small bilayered ducts and pseudocysts, and frequent perineural invasion.
- Ancillary: Immunohistochemistry shows diffuse positivity for broad-spectrum keratins, CAM5.2, and CK7, with nuclear staining for SOX10 in basaloid and myoepithelial cells.
Reference Gallery:
Adenoid cystic carcinoma. Cribriform, tubular, and solid patterns are typical of this neoplasm, as is perineural or intraneural invasion.
Adenoid cystic carcinoma. Perineural and intraneural invasion.
Adenoid cystic carcinoma. The essential diagnostic feature is the coexistence of true small bilayered ducts and pseudocysts.
Adenoid cystic carcinoma. Areas with myoepithelial differentiation stain positively for α-SMA.

Q: In Adenoid Cystic Carcinoma, areas demonstrating myoepithelial differentiation will typically stain positively for the immunohistochemical marker [...].
Adenoid cystic carcinoma. Areas with myoepithelial differentiation stain positively for α-SMA.
A: α-SMA
Back Extra: Adenoid Cystic Carcinoma
- Clinical: Adenoid cystic carcinoma (AdCC) typically presents as a solitary nodule, often present for several years, and is more common in middle-aged to elderly individuals with a slight female predilection.
- Micro: Key microscopic features include a mixture of cribriform, tubular, and solid patterns, with true small bilayered ducts and pseudocysts, and frequent perineural invasion.
- Ancillary: Immunohistochemistry shows diffuse positivity for broad-spectrum keratins, CAM5.2, and CK7, with nuclear staining for SOX10 in basaloid and myoepithelial cells.
Reference Gallery:
Adenoid cystic carcinoma. Cribriform, tubular, and solid patterns are typical of this neoplasm, as is perineural or intraneural invasion.
Adenoid cystic carcinoma. Perineural and intraneural invasion.
Adenoid cystic carcinoma. The essential diagnostic feature is the coexistence of true small bilayered ducts and pseudocysts.
Adenoid cystic carcinoma. Areas with myoepithelial differentiation stain positively for α-SMA.

Q: A well-circumscribed dermal tumor composed of a mixture of clear cells, eosinophilic cells, and ductal structures is microscopically characteristic of a [...].
Hidradenoma. A well-circumscribed neoplasm composed mainly of clear cells admixed with ductal structures.
Hidradenoma. The tumour is composed of a mixture of clear and eosinophilic cells.
A: hidradenoma
Back Extra: Hidradenoma
- Clinical: Hidradenoma is an asymptomatic, solitary, firm nodule, usually < 20–30 mm in diameter, primarily located on the trunk and limbs.
- Micro: Hidradenomas are well-circumscribed dermal neoplasms composed of clear cells and ductal structures, with a characteristic hyalinized stroma.
- Ancillary: Hidradenomas often harbor a t(11;19) translocation, leading to the fusion of CRTC1 (MECT1) with MAML2, which activates downstream cAMP/CREB signalling genes.
Reference Gallery:
Hidradenoma. A well-circumscribed neoplasm composed mainly of clear cells admixed with ductal structures.
Hidradenoma. The tumour is composed of a mixture of clear and eosinophilic cells.
Atypical hidradenoma metastatic to lymph node. The primary tumour and the lymph node show overlapping features, consisting of a proliferation with a lobular architecture and extensive cystic changes containing pink amorphous material.

Q: At the molecular level, hidradenoma frequently harbors a pathognomonic [...] translocation, leading to the fusion of CRTC1 with MAML2.
Hidradenoma. A well-circumscribed neoplasm composed mainly of clear cells admixed with ductal structures.
A: t(11;19)
Back Extra: Hidradenoma
- Clinical: Hidradenoma is an asymptomatic, solitary, firm nodule, usually < 20–30 mm in diameter, primarily located on the trunk and limbs.
- Micro: Hidradenomas are well-circumscribed dermal neoplasms composed of clear cells and ductal structures, with a characteristic hyalinized stroma.
- Ancillary: Hidradenomas often harbor a t(11;19) translocation, leading to the fusion of CRTC1 (MECT1) with MAML2, which activates downstream cAMP/CREB signalling genes.
Reference Gallery:
Hidradenoma. A well-circumscribed neoplasm composed mainly of clear cells admixed with ductal structures.
Hidradenoma. The tumour is composed of a mixture of clear and eosinophilic cells.
Atypical hidradenoma metastatic to lymph node. The primary tumour and the lymph node show overlapping features, consisting of a proliferation with a lobular architecture and extensive cystic changes containing pink amorphous material.

Q: The apocrine pattern of a Mixed Tumor typically presents as a well-circumscribed dermal neoplasm featuring branched tubules embedded in a characteristic [...] stroma.
Mixed tumour (apocrine). A well-circumscribed dermal neoplasm composed of tubules embedded in a myxoid stroma.
A: myxoid
Back Extra: Mixed Tumour
- Clinical: Mixed tumours are typically solitary, well-circumscribed nodules, most commonly found on the scalp and face.
- Micro: The apocrine pattern of mixed tumour is characterized by elongated, branched tubules and cystic spaces lined by two layers of cells: cuboidal myoepithelial cells and columnar cells.
- Ancillary: Mixed tumours often express SOX10, p63, S100, calponin, SMA, EMA, KIT, CEA, various cytokeratins, and PLAG1 (except in the eccrine pattern).
Reference Gallery:
Mixed tumour (apocrine). A well-circumscribed dermal neoplasm composed of tubules embedded in a myxoid stroma.
Mixed tumour (apocrine). The tumour is composed of tubules lined by two or more rows of cuboidal cells with eosinophilic cytoplasm.
Mixed tumour (eccrine). A well-circumscribed deep dermal neoplasm composed mainly of round tubules embedded in a chondroid stroma.
Mixed tumour (eccrine). Detail of the tubules and the chondroid stroma.

Q: The eccrine pattern of a Mixed Tumor is distinctively characterized by round tubules embedded in a prominent [...] stroma.
Mixed tumour (eccrine). A well-circumscribed deep dermal neoplasm composed mainly of round tubules embedded in a chondroid stroma.
Mixed tumour (eccrine). Detail of the tubules and the chondroid stroma.
A: chondroid
Back Extra: Mixed Tumour
- Clinical: Mixed tumours are typically solitary, well-circumscribed nodules, most commonly found on the scalp and face.
- Micro: The apocrine pattern of mixed tumour is characterized by elongated, branched tubules and cystic spaces lined by two layers of cells: cuboidal myoepithelial cells and columnar cells.
- Ancillary: Mixed tumours often express SOX10, p63, S100, calponin, SMA, EMA, KIT, CEA, various cytokeratins, and PLAG1 (except in the eccrine pattern).
Reference Gallery:
Mixed tumour (apocrine). A well-circumscribed dermal neoplasm composed of tubules embedded in a myxoid stroma.
Mixed tumour (apocrine). The tumour is composed of tubules lined by two or more rows of cuboidal cells with eosinophilic cytoplasm.
Mixed tumour (eccrine). A well-circumscribed deep dermal neoplasm composed mainly of round tubules embedded in a chondroid stroma.
Mixed tumour (eccrine). Detail of the tubules and the chondroid stroma.

Q: In the apocrine variant of a Mixed Tumor, the tubules are characteristically lined by an inner layer of columnar cells and an outer layer of cuboidal [...] cells.
Mixed tumour (apocrine). The tumour is composed of tubules lined by two or more rows of cuboidal cells with eosinophilic cytoplasm.
A: myoepithelial
Back Extra: Mixed Tumour
- Clinical: Mixed tumours are typically solitary, well-circumscribed nodules, most commonly found on the scalp and face.
- Micro: The apocrine pattern of mixed tumour is characterized by elongated, branched tubules and cystic spaces lined by two layers of cells: cuboidal myoepithelial cells and columnar cells.
- Ancillary: Mixed tumours often express SOX10, p63, S100, calponin, SMA, EMA, KIT, CEA, various cytokeratins, and PLAG1 (except in the eccrine pattern).
Reference Gallery:
Mixed tumour (apocrine). A well-circumscribed dermal neoplasm composed of tubules embedded in a myxoid stroma.
Mixed tumour (apocrine). The tumour is composed of tubules lined by two or more rows of cuboidal cells with eosinophilic cytoplasm.
Mixed tumour (eccrine). A well-circumscribed deep dermal neoplasm composed mainly of round tubules embedded in a chondroid stroma.
Mixed tumour (eccrine). Detail of the tubules and the chondroid stroma.

Q: Patients with Brooke–Spiegler Syndrome frequently present with multiple cutaneous adnexal tumors, most notably spiradenomas, trichoepitheliomas, and [...] (which often present as prominent nodules on the scalp and ears).
Brooke–Spiegler syndrome. Clinical appearance of scalp cylindromas in a patient with Brooke–Spiegler syndrome.
Brooke–Spiegler syndrome. Clustered auricular cylindroma in a patient with Brooke–Spiegler syndrome. The ear is a favoured site.
A: cylindromas
Brooke–Spiegler Syndrome
- Clinical: Patients with Brooke–Spiegler Syndrome often present with multiple cutaneous spiradenomas, cylindromas, and trichoepitheliomas that are typically skin-coloured, reddish, or blue and grow throughout life.
- Micro: Cutaneous tumours in Brooke–Spiegler Syndrome show a jigsaw-puzzle (mosaic-like) arrangement of islands of basaloid cells surrounded by variably thickened eosinophilic basement membrane material.
- Ancillary: Diagnosis of Brooke–Spiegler Syndrome can be confirmed by identifying biallelic pathogenic variants in CYLD.
Reference Gallery:
Cutaneous cylindroma in Brooke–Spiegler syndrome. Low magnification showing irregular tumour nests surrounded by eosinophilic and hyaline basement membrane.
Cutaneous cylindroma in Brooke–Spiegler syndrome. High magnification showing prominent droplets of hyaline materials and duct-like structures within the tumour nests.
Brooke–Spiegler syndrome. Clinical appearance of scalp cylindromas in a patient with Brooke–Spiegler syndrome.
Basal cell adenoma in Brooke–Spiegler syndrome. Low-power view showing a well-circumscribed parotid basal cell adenoma, present in a patient with Brooke–Spiegler syndrome / familial cylindromatosis.
Membranous basal cell adenoma. Salivary gland involvement in Brooke–Spiegler syndrome is characterized by the presence of basal cell adenoma, membranous type, which appears identical to cutaneous cylindroma. The tumour nests show the characteristic peripheral palisading of dark cells, with paler cells separated by dense hyaline stroma.
Parotid tumour in Brooke–Spiegler syndrome. Salivary gland involvement is characterized by the presence of multicentric membranous basal cell adenomas. These tumours are usually bilateral/multicentric and well-circumscribed. The tumour nests show the characteristic peripheral palisading of dark cells, with paler cells located more centrally within these nests. The cells nests are separated by dense hyaline stroma.
Brooke–Spiegler syndrome. Clustered auricular cylindroma in a patient with Brooke–Spiegler syndrome. The ear is a favoured site.

Q: Histologically, the cutaneous cylindromas seen in Brooke–Spiegler Syndrome classically exhibit a [...] (or mosaic-like) arrangement of basaloid cell islands surrounded by variably thickened, eosinophilic basement membrane material.
Cutaneous cylindroma in Brooke–Spiegler syndrome. Low magnification showing irregular tumour nests surrounded by eosinophilic and hyaline basement membrane.
Cutaneous cylindroma in Brooke–Spiegler syndrome. High magnification showing prominent droplets of hyaline materials and duct-like structures within the tumour nests.
A: jigsaw-puzzle
Brooke–Spiegler Syndrome
- Clinical: Patients with Brooke–Spiegler Syndrome often present with multiple cutaneous spiradenomas, cylindromas, and trichoepitheliomas that are typically skin-coloured, reddish, or blue and grow throughout life.
- Micro: Cutaneous tumours in Brooke–Spiegler Syndrome show a jigsaw-puzzle (mosaic-like) arrangement of islands of basaloid cells surrounded by variably thickened eosinophilic basement membrane material.
- Ancillary: Diagnosis of Brooke–Spiegler Syndrome can be confirmed by identifying biallelic pathogenic variants in CYLD.
Reference Gallery:
Cutaneous cylindroma in Brooke–Spiegler syndrome. Low magnification showing irregular tumour nests surrounded by eosinophilic and hyaline basement membrane.
Cutaneous cylindroma in Brooke–Spiegler syndrome. High magnification showing prominent droplets of hyaline materials and duct-like structures within the tumour nests.
Brooke–Spiegler syndrome. Clinical appearance of scalp cylindromas in a patient with Brooke–Spiegler syndrome.
Basal cell adenoma in Brooke–Spiegler syndrome. Low-power view showing a well-circumscribed parotid basal cell adenoma, present in a patient with Brooke–Spiegler syndrome / familial cylindromatosis.
Membranous basal cell adenoma. Salivary gland involvement in Brooke–Spiegler syndrome is characterized by the presence of basal cell adenoma, membranous type, which appears identical to cutaneous cylindroma. The tumour nests show the characteristic peripheral palisading of dark cells, with paler cells separated by dense hyaline stroma.
Parotid tumour in Brooke–Spiegler syndrome. Salivary gland involvement is characterized by the presence of multicentric membranous basal cell adenomas. These tumours are usually bilateral/multicentric and well-circumscribed. The tumour nests show the characteristic peripheral palisading of dark cells, with paler cells located more centrally within these nests. The cells nests are separated by dense hyaline stroma.
Brooke–Spiegler syndrome. Clustered auricular cylindroma in a patient with Brooke–Spiegler syndrome. The ear is a favoured site.

Q: Salivary gland tumors associated with Brooke–Spiegler Syndrome are classically multicentric [...], which appear microscopically identical to cutaneous cylindromas with prominent peripheral palisading and dense hyaline stroma.
Membranous basal cell adenoma. Salivary gland involvement in Brooke–Spiegler syndrome is characterized by the presence of basal cell adenoma, membranous type, which appears identical to cutaneous cylindroma. The tumour nests show the characteristic peripheral palisading of dark cells, with paler cells separated by dense hyaline stroma.
Parotid tumour in Brooke–Spiegler syndrome. Salivary gland involvement is characterized by the presence of multicentric membranous basal cell adenomas. These tumours are usually bilateral/multicentric and well-circumscribed. The tumour nests show the characteristic peripheral palisading of dark cells, with paler cells located more centrally within these nests. The cells nests are separated by dense hyaline stroma.
A: membranous basal cell adenomas
Brooke–Spiegler Syndrome
- Clinical: Patients with Brooke–Spiegler Syndrome often present with multiple cutaneous spiradenomas, cylindromas, and trichoepitheliomas that are typically skin-coloured, reddish, or blue and grow throughout life.
- Micro: Cutaneous tumours in Brooke–Spiegler Syndrome show a jigsaw-puzzle (mosaic-like) arrangement of islands of basaloid cells surrounded by variably thickened eosinophilic basement membrane material.
- Ancillary: Diagnosis of Brooke–Spiegler Syndrome can be confirmed by identifying biallelic pathogenic variants in CYLD.
Reference Gallery:
Cutaneous cylindroma in Brooke–Spiegler syndrome. Low magnification showing irregular tumour nests surrounded by eosinophilic and hyaline basement membrane.
Cutaneous cylindroma in Brooke–Spiegler syndrome. High magnification showing prominent droplets of hyaline materials and duct-like structures within the tumour nests.
Brooke–Spiegler syndrome. Clinical appearance of scalp cylindromas in a patient with Brooke–Spiegler syndrome.
Basal cell adenoma in Brooke–Spiegler syndrome. Low-power view showing a well-circumscribed parotid basal cell adenoma, present in a patient with Brooke–Spiegler syndrome / familial cylindromatosis.
Membranous basal cell adenoma. Salivary gland involvement in Brooke–Spiegler syndrome is characterized by the presence of basal cell adenoma, membranous type, which appears identical to cutaneous cylindroma. The tumour nests show the characteristic peripheral palisading of dark cells, with paler cells separated by dense hyaline stroma.
Parotid tumour in Brooke–Spiegler syndrome. Salivary gland involvement is characterized by the presence of multicentric membranous basal cell adenomas. These tumours are usually bilateral/multicentric and well-circumscribed. The tumour nests show the characteristic peripheral palisading of dark cells, with paler cells located more centrally within these nests. The cells nests are separated by dense hyaline stroma.
Brooke–Spiegler syndrome. Clustered auricular cylindroma in a patient with Brooke–Spiegler syndrome. The ear is a favoured site.

Q: Microscopically, a Cylindroma features aggregates of basaloid cells surrounded by a prominent basement membrane, which creates a highly characteristic [...] arrangement.
Cylindroma. There are collections of basaloid epithelial cells in the dermis, surrounded by prominent basement membrane material, which has been described as a jigsaw-puzzle arrangement.
Cylindroma. Detail of the basaloid cells and areas of ductal differentiation.
A: jigsaw-puzzle
Back Extra: Cylindroma
- Clinical: Cylindromas are typically smooth, dome-shaped, hairless, reddish-brown papules or nodules, most commonly affecting the head and neck.
- Micro: Cylindroma is characterized by multiple aggregates of basaloid cells in a jigsaw-puzzle arrangement, surrounded by a prominent basement membrane.
- Ancillary: Immunohistochemistry shows expression of KIT (CD117) and SOX10, and MYB overexpression may also be observed.
Reference Gallery:
Cylindroma. There are collections of basaloid epithelial cells in the dermis, surrounded by prominent basement membrane material, which has been described as a jigsaw-puzzle arrangement.
Cylindroma. Detail of the basaloid cells and areas of ductal differentiation.
Solitary spiradenocylindroma. The lesion appears as a firm, erythematous nodule with a smooth surface.
Solitary spiradenocylindroma. By dermoscopy, solitary spiradenocylindroma shows a nonspecific vascular pattern.

Q: The interlocking "jigsaw-puzzle" pattern of a Cylindroma is formed by nests of basaloid cells that are tightly surrounded and separated by thickened, prominent [...] material.
Cylindroma. There are collections of basaloid epithelial cells in the dermis, surrounded by prominent basement membrane material, which has been described as a jigsaw-puzzle arrangement.
Cylindroma. Detail of the basaloid cells and areas of ductal differentiation.
A: basement membrane
Back Extra: Cylindroma
- Clinical: Cylindromas are typically smooth, dome-shaped, hairless, reddish-brown papules or nodules, most commonly affecting the head and neck.
- Micro: Cylindroma is characterized by multiple aggregates of basaloid cells in a jigsaw-puzzle arrangement, surrounded by a prominent basement membrane.
- Ancillary: Immunohistochemistry shows expression of KIT (CD117) and SOX10, and MYB overexpression may also be observed.
Reference Gallery:
Cylindroma. There are collections of basaloid epithelial cells in the dermis, surrounded by prominent basement membrane material, which has been described as a jigsaw-puzzle arrangement.
Cylindroma. Detail of the basaloid cells and areas of ductal differentiation.
Solitary spiradenocylindroma. The lesion appears as a firm, erythematous nodule with a smooth surface.
Solitary spiradenocylindroma. By dermoscopy, solitary spiradenocylindroma shows a nonspecific vascular pattern.

Q: Clinically, Digital Papillary Adenocarcinoma typically presents as an asymptomatic, slow-growing, deep-seated nodule preferentially located on [...] sites.
Digital papillary adenocarcinoma. Presentation as an asymmetrical deep-seated nodule.
Digital papillary adenocarcinoma. Gross examination of a digital papillary adenocarcinoma.
A: acral
Back Extra: Digital Papillary Adenocarcinoma
- Clinical: Digital papillary adenocarcinoma typically presents as a slow-growing, asymptomatic, deep-seated nodule on acral sites.
- Micro: The lesion is multinodular and shows a mix of solid, cystic, and papillary growth patterns with glandular structures and nuclear pleomorphism.
- Ancillary: The tumour cells are diffusely positive for pancytokeratin and CK7, with a recognizable layer of SMA-positive myoepithelial cells.
Reference Gallery:
Digital papillary adenocarcinoma. A multinodular, poorly circumscribed neoplasm exhibiting solid, cystic, and papillary areas.
Digital papillary adenocarcinoma. A multinodular, poorly circumscribed neoplasm exhibiting solid, cystic, and papillary areas.
Digital papillary adenocarcinoma. Presentation as an asymmetrical deep-seated nodule.
Digital papillary adenocarcinoma. Glandular structures can be prominent.
Digital papillary adenocarcinoma. Note the nuclear pleomorphism and mitotic figures.
Digital papillary adenocarcinoma. Staining for α-SMA reveals a myoepithelial cell layer around glands. There is focal loss of the surrounding SMA-positive myoepithelial cell layer (arrow).
Digital papillary adenocarcinoma. Gross examination of a digital papillary adenocarcinoma.
Digital papillary adenocarcinoma. Gross examination of a digital papillary adenocarcinoma.

Q: The microscopic appearance of Digital Papillary Adenocarcinoma typically reveals a multinodular, poorly circumscribed tumor exhibiting a characteristic mix of solid, cystic, and [...] growth patterns.
Digital papillary adenocarcinoma. A multinodular, poorly circumscribed neoplasm exhibiting solid, cystic, and papillary areas.
Digital papillary adenocarcinoma. A multinodular, poorly circumscribed neoplasm exhibiting solid, cystic, and papillary areas.
A: papillary
Back Extra: Digital Papillary Adenocarcinoma
- Clinical: Digital papillary adenocarcinoma typically presents as a slow-growing, asymptomatic, deep-seated nodule on acral sites.
- Micro: The lesion is multinodular and shows a mix of solid, cystic, and papillary growth patterns with glandular structures and nuclear pleomorphism.
- Ancillary: The tumour cells are diffusely positive for pancytokeratin and CK7, with a recognizable layer of SMA-positive myoepithelial cells.
Reference Gallery:
Digital papillary adenocarcinoma. A multinodular, poorly circumscribed neoplasm exhibiting solid, cystic, and papillary areas.
Digital papillary adenocarcinoma. A multinodular, poorly circumscribed neoplasm exhibiting solid, cystic, and papillary areas.
Digital papillary adenocarcinoma. Presentation as an asymmetrical deep-seated nodule.
Digital papillary adenocarcinoma. Glandular structures can be prominent.
Digital papillary adenocarcinoma. Note the nuclear pleomorphism and mitotic figures.
Digital papillary adenocarcinoma. Staining for α-SMA reveals a myoepithelial cell layer around glands. There is focal loss of the surrounding SMA-positive myoepithelial cell layer (arrow).
Digital papillary adenocarcinoma. Gross examination of a digital papillary adenocarcinoma.
Digital papillary adenocarcinoma. Gross examination of a digital papillary adenocarcinoma.

Q: To help confirm the diagnosis of invasive Digital Papillary Adenocarcinoma, immunostaining for alpha-SMA often reveals a recognizable layer of myoepithelial cells around the glandular structures that demonstrates focal [...].
Digital papillary adenocarcinoma. Staining for α-SMA reveals a myoepithelial cell layer around glands. There is focal loss of the surrounding SMA-positive myoepithelial cell layer (arrow).
A: loss
Back Extra: Digital Papillary Adenocarcinoma
- Clinical: Digital papillary adenocarcinoma typically presents as a slow-growing, asymptomatic, deep-seated nodule on acral sites.
- Micro: The lesion is multinodular and shows a mix of solid, cystic, and papillary growth patterns with glandular structures and nuclear pleomorphism.
- Ancillary: The tumour cells are diffusely positive for pancytokeratin and CK7, with a recognizable layer of SMA-positive myoepithelial cells.
Reference Gallery:
Digital papillary adenocarcinoma. A multinodular, poorly circumscribed neoplasm exhibiting solid, cystic, and papillary areas.
Digital papillary adenocarcinoma. A multinodular, poorly circumscribed neoplasm exhibiting solid, cystic, and papillary areas.
Digital papillary adenocarcinoma. Presentation as an asymmetrical deep-seated nodule.
Digital papillary adenocarcinoma. Glandular structures can be prominent.
Digital papillary adenocarcinoma. Note the nuclear pleomorphism and mitotic figures.
Digital papillary adenocarcinoma. Staining for α-SMA reveals a myoepithelial cell layer around glands. There is focal loss of the surrounding SMA-positive myoepithelial cell layer (arrow).
Digital papillary adenocarcinoma. Gross examination of a digital papillary adenocarcinoma.
Digital papillary adenocarcinoma. Gross examination of a digital papillary adenocarcinoma.

Q: Microscopically, Endocrine Mucin-Producing Sweat Gland Carcinoma features expansile nests of intermediate-sized cells with finely stippled chromatin and characteristic [...] cytoplasm that form solid, cystic, cribriform, and pseudopapillary patterns.
Endocrine mucin-producing sweat gland carcinoma. Low-magnification view showing expansile nests of bluish cells forming solid, cystic, and pseudopapillary patterns.
Endocrine mucin-producing sweat gland carcinoma. Tumour nest with a cribriform and cystic pattern.
Endocrine mucin-producing sweat gland carcinoma. A papilla with a vascular core. The tumour cells are intermediate-sized round, oval, and polygonal epithelial cells with bluish cytoplasm and oval nuclei showing inconspicuous nucleoli and finely stippled chromatin. Only rarely do tumours show more pleomorphism than in this lesion.
A: bluish
Back Extra: Endocrine Mucin-Producing Sweat Gland Carcinoma
- Clinical: Patients with Endocrine Mucin-Producing Sweat Gland Carcinoma present with a slow-growing, skin-coloured or bluish nodule, papule, or cyst, typically on the eyelid/periorbital skin, with a higher incidence in women.
- Micro: Endocrine Mucin-Producing Sweat Gland Carcinoma grows as expansile nodules with cystic, solid, papillary, and pseudopapillary patterns, showing bluish cells and intracellular/extracellular mucin.
- Ancillary: INSM1, ER, PR, and CK7 are strongly positive in Endocrine Mucin-Producing Sweat Gland Carcinoma, while synaptophysin or chromogranin expression can be focal or absent.
Reference Gallery:
Endocrine mucin-producing sweat gland carcinoma. Low-magnification view showing expansile nests of bluish cells forming solid, cystic, and pseudopapillary patterns.
Endocrine mucin-producing sweat gland carcinoma. Tumour nest with a cribriform and cystic pattern.
Endocrine mucin-producing sweat gland carcinoma. A papilla with a vascular core. The tumour cells are intermediate-sized round, oval, and polygonal epithelial cells with bluish cytoplasm and oval nuclei showing inconspicuous nucleoli and finely stippled chromatin. Only rarely do tumours show more pleomorphism than in this lesion.
Endocrine mucin-producing sweat gland carcinoma in situ. An early tumour arising in a dilated eccrine duct / hidrocystoma.
Endocrine mucin-producing sweat gland carcinoma. The presence of infiltrating nests associated with stromal mucin indicates early progression to mucinous carcinoma.

Q: While Endocrine Mucin-Producing Sweat Gland Carcinoma typically forms expansile nodules, the presence of infiltrating tumor nests associated with extracellular stromal mucin indicates early progression to [...].
Endocrine mucin-producing sweat gland carcinoma. The presence of infiltrating nests associated with stromal mucin indicates early progression to mucinous carcinoma.
A: mucinous carcinoma
Back Extra: Endocrine Mucin-Producing Sweat Gland Carcinoma
- Clinical: Patients with Endocrine Mucin-Producing Sweat Gland Carcinoma present with a slow-growing, skin-coloured or bluish nodule, papule, or cyst, typically on the eyelid/periorbital skin, with a higher incidence in women.
- Micro: Endocrine Mucin-Producing Sweat Gland Carcinoma grows as expansile nodules with cystic, solid, papillary, and pseudopapillary patterns, showing bluish cells and intracellular/extracellular mucin.
- Ancillary: INSM1, ER, PR, and CK7 are strongly positive in Endocrine Mucin-Producing Sweat Gland Carcinoma, while synaptophysin or chromogranin expression can be focal or absent.
Reference Gallery:
Endocrine mucin-producing sweat gland carcinoma. Low-magnification view showing expansile nests of bluish cells forming solid, cystic, and pseudopapillary patterns.
Endocrine mucin-producing sweat gland carcinoma. Tumour nest with a cribriform and cystic pattern.
Endocrine mucin-producing sweat gland carcinoma. A papilla with a vascular core. The tumour cells are intermediate-sized round, oval, and polygonal epithelial cells with bluish cytoplasm and oval nuclei showing inconspicuous nucleoli and finely stippled chromatin. Only rarely do tumours show more pleomorphism than in this lesion.
Endocrine mucin-producing sweat gland carcinoma in situ. An early tumour arising in a dilated eccrine duct / hidrocystoma.
Endocrine mucin-producing sweat gland carcinoma. The presence of infiltrating nests associated with stromal mucin indicates early progression to mucinous carcinoma.

Q: The provided images demonstrate high-grade [...], an aggressive sweat gland tumor characterized by nuclear pleomorphism, abnormal mitotic figures, infiltrative growth, and a predominance of clear cells or squamoid cells.
High-grade hidradenocarcinoma. This neoplasm has a predominance of relatively bland clear cells admixed with highly pleomorphic, sometimes multinucleated bizarre cells exhibiting abnormal mitotic figures.
High-grade hidradenocarcinoma. This neoplasm has a predominance of relatively bland clear cells admixed with highly pleomorphic, sometimes multinucleated bizarre cells exhibiting abnormal mitotic figures. High-power view shows frankly anaplastic areas.
A: hidradenocarcinoma
Back Extra: Hidradenocarcinoma
- Clinical: Hidradenocarcinoma is a solitary tumour varying in size from 10 to 60 mm, often presenting in the head and neck region, and is more common in males in their fifth to seventh decade of life.
- Micro: Hidradenocarcinoma is characterized by nuclear pleomorphism, increased mitotic activity, an infiltrative growth pattern, necrosis, and perineural and lymphovascular invasion, often with a predominance of clear cells or squamoid cells.
- Ancillary: CEA and EMA stain the luminal borders of ductal structures, and CRTC1::MAML2 fusions are diagnostic but rare. TP53 mutations are found in fewer than 20% of cases.
Reference Gallery:
High-grade hidradenocarcinoma. This neoplasm has a predominance of relatively bland clear cells admixed with highly pleomorphic, sometimes multinucleated bizarre cells exhibiting abnormal mitotic figures.
High-grade hidradenocarcinoma. This neoplasm has a predominance of relatively bland clear cells admixed with highly pleomorphic, sometimes multinucleated bizarre cells exhibiting abnormal mitotic figures. High-power view shows frankly anaplastic areas.

Q: Morphologically, hidradenocarcinoma is a malignant tumor that often exhibits an infiltrative growth pattern with a predominance of squamoid cells or [...], which may be admixed with frankly anaplastic areas and multinucleated bizarre cells.
High-grade hidradenocarcinoma. This neoplasm has a predominance of relatively bland clear cells admixed with highly pleomorphic, sometimes multinucleated bizarre cells exhibiting abnormal mitotic figures.
High-grade hidradenocarcinoma. This neoplasm has a predominance of relatively bland clear cells admixed with highly pleomorphic, sometimes multinucleated bizarre cells exhibiting abnormal mitotic figures. High-power view shows frankly anaplastic areas.
A: clear cells
Back Extra: Hidradenocarcinoma
- Clinical: Hidradenocarcinoma is a solitary tumour varying in size from 10 to 60 mm, often presenting in the head and neck region, and is more common in males in their fifth to seventh decade of life.
- Micro: Hidradenocarcinoma is characterized by nuclear pleomorphism, increased mitotic activity, an infiltrative growth pattern, necrosis, and perineural and lymphovascular invasion, often with a predominance of clear cells or squamoid cells.
- Ancillary: CEA and EMA stain the luminal borders of ductal structures, and CRTC1::MAML2 fusions are diagnostic but rare. TP53 mutations are found in fewer than 20% of cases.
Reference Gallery:
High-grade hidradenocarcinoma. This neoplasm has a predominance of relatively bland clear cells admixed with highly pleomorphic, sometimes multinucleated bizarre cells exhibiting abnormal mitotic figures.
High-grade hidradenocarcinoma. This neoplasm has a predominance of relatively bland clear cells admixed with highly pleomorphic, sometimes multinucleated bizarre cells exhibiting abnormal mitotic figures. High-power view shows frankly anaplastic areas.

Q: The defining microscopic feature of a Malignant Mixed Tumor is the presence of a malignant component (e.g., adenocarcinoma or myoepithelial carcinoma) arising in direct association with a pre-existing [...].
Malignant mixed tumour. This part of the neoplasm exhibits features of apocrine mixed tumour (the pre-existing lesion).
Malignant mixed tumour. There is transformation to adenocarcinoma. Note the atypical cells in the tubular areas.
Malignant mixed tumour. In this example, the malignant component has a sarcomatous appearance.
A: benign mixed tumor
Back Extra: Malignant Mixed Tumour
- Clinical: Malignant Mixed Tumours are rare and typically occur as solitary nodules in the elderly, often with a history of rapid growth.
- Micro: The presence of a benign mixed tumour (usually apocrine) in association with a malignant component, which can be adenocarcinoma, myoepithelial carcinoma, or sarcomatoid, is diagnostic.
- Ancillary: FISH studies may show PLAG1 rearrangements in the benign component, and additional chromosomal changes in the malignant areas, such as loss of 17p and 19p.
Reference Gallery:
Malignant mixed tumour. This part of the neoplasm exhibits features of apocrine mixed tumour (the pre-existing lesion).
Malignant mixed tumour. There is transformation to adenocarcinoma. Note the atypical cells in the tubular areas.
Malignant mixed tumour. In this example, the malignant component has a sarcomatous appearance.

Q: In Malignant Mixed Tumor, the malignant component arising from the benign precursor lesion may take the form of an adenocarcinoma, myoepithelial carcinoma, or exhibit a [...] appearance.
Malignant mixed tumour. There is transformation to adenocarcinoma. Note the atypical cells in the tubular areas.
Malignant mixed tumour. In this example, the malignant component has a sarcomatous appearance.
A: sarcomatous
Back Extra: Malignant Mixed Tumour
- Clinical: Malignant Mixed Tumours are rare and typically occur as solitary nodules in the elderly, often with a history of rapid growth.
- Micro: The presence of a benign mixed tumour (usually apocrine) in association with a malignant component, which can be adenocarcinoma, myoepithelial carcinoma, or sarcomatoid, is diagnostic.
- Ancillary: FISH studies may show PLAG1 rearrangements in the benign component, and additional chromosomal changes in the malignant areas, such as loss of 17p and 19p.
Reference Gallery:
Malignant mixed tumour. This part of the neoplasm exhibits features of apocrine mixed tumour (the pre-existing lesion).
Malignant mixed tumour. There is transformation to adenocarcinoma. Note the atypical cells in the tubular areas.
Malignant mixed tumour. In this example, the malignant component has a sarcomatous appearance.

Q: Microscopically, Malignant Neoplasms Arising from Spiradenoma, Cylindroma, or Spiradenocylindroma feature a transition from a benign parent lesion to a malignant component that classically demonstrates increased mitoses, cytological atypia, and a [...].
Malignant neoplasm arising in pre-existing spiradenoma. The transition between the benign parent lesion and the evolving malignant neoplasm.
Malignant neoplasm arising in pre-existing spiradenoma. Higher magnification shows that the low-grade malignant area is characterized by loss of the dual cell differentiation, mild to moderate cytological atypia with nuclear crowding, and mitotic activity.
A: loss of the dual cell population
Back Extra: Malignant Neoplasms Arising from Spiradenoma, Cylindroma, or Spiradenocylindroma
- Clinical: Malignant neoplasms arising from spiradenoma, cylindroma, or spiradenocylindroma typically present as large nodules, with median size around 40 mm, and can show rapid growth in longstanding lesions.
- Micro: The tumours show a gradual or abrupt transition from the benign parent lesion (spiradenoma, cylindroma, or spiradenocylindroma) to the malignant component, characterized by loss of dual cell population, cytological atypia, and increased mitotic activity.
- Ancillary: MYB expression is lost in the malignant counterparts, and the Ki-67 proliferation index is increased in the malignant areas.
Reference Gallery:
High-grade basal cell adenocarcinoma arising in a pre-existing spiradenoma. A residuum of spiradenoma can be seen at the lower left. The malignant portion is composed of medium-sized to large pleomorphic basaloid cells with numerous atypical mitotic figures and necrotic cells, presenting as confluent sheets and nodules with an infiltrative growth pattern (basal cell adenocarcinoma–like pattern, high grade).
High-grade basal cell adenocarcinoma arising in a pre-existing spiradenoma. The malignant portion is composed of medium-sized to large pleomorphic basaloid cells with numerous atypical mitotic figures and necrotic cells, presenting as confluent sheets and nodules with an infiltrative growth pattern (basal cell adenocarcinoma–like pattern, high grade).
Invasive adenocarcinoma NOS arising from pre-existing spiradenoma. This tumour shows highly atypical cells arranged in an alveolar pattern, with occasional lumina.
Several malignant patterns, including sarcomatoid carcinoma, in a pre-existing spiradenoma. Note the transition from the atypical basaloid component to a sarcomatoid component.
Several malignant patterns, including sarcomatoid carcinoma, in a pre-existing spiradenoma. Note the transition from the atypical basaloid component to a sarcomatoid component.
Malignant neoplasm arising in pre-existing spiradenoma. The transition between the benign parent lesion and the evolving malignant neoplasm.
Malignant neoplasm arising in pre-existing spiradenoma. Higher magnification shows that the low-grade malignant area is characterized by loss of the dual cell differentiation, mild to moderate cytological atypia with nuclear crowding, and mitotic activity.

Q: The diagnosis of [...] should be considered when a biopsy of a longstanding adnexal nodule shows an abrupt or gradual transition into an aggressive component, such as a high-grade basal cell adenocarcinoma-like, invasive adenocarcinoma NOS, or sarcomatoid carcinoma pattern.
High-grade basal cell adenocarcinoma arising in a pre-existing spiradenoma. A residuum of spiradenoma can be seen at the lower left. The malignant portion is composed of medium-sized to large pleomorphic basaloid cells with numerous atypical mitotic figures and necrotic cells, presenting as confluent sheets and nodules with an infiltrative growth pattern (basal cell adenocarcinoma–like pattern, high grade).
Invasive adenocarcinoma NOS arising from pre-existing spiradenoma. This tumour shows highly atypical cells arranged in an alveolar pattern, with occasional lumina.
Several malignant patterns, including sarcomatoid carcinoma, in a pre-existing spiradenoma. Note the transition from the atypical basaloid component to a sarcomatoid component.
A: Malignant Neoplasms Arising from Spiradenoma, Cylindroma, or Spiradenocylindroma
Back Extra: Malignant Neoplasms Arising from Spiradenoma, Cylindroma, or Spiradenocylindroma
- Clinical: Malignant neoplasms arising from spiradenoma, cylindroma, or spiradenocylindroma typically present as large nodules, with median size around 40 mm, and can show rapid growth in longstanding lesions.
- Micro: The tumours show a gradual or abrupt transition from the benign parent lesion (spiradenoma, cylindroma, or spiradenocylindroma) to the malignant component, characterized by loss of dual cell population, cytological atypia, and increased mitotic activity.
- Ancillary: MYB expression is lost in the malignant counterparts, and the Ki-67 proliferation index is increased in the malignant areas.
Reference Gallery:
High-grade basal cell adenocarcinoma arising in a pre-existing spiradenoma. A residuum of spiradenoma can be seen at the lower left. The malignant portion is composed of medium-sized to large pleomorphic basaloid cells with numerous atypical mitotic figures and necrotic cells, presenting as confluent sheets and nodules with an infiltrative growth pattern (basal cell adenocarcinoma–like pattern, high grade).
High-grade basal cell adenocarcinoma arising in a pre-existing spiradenoma. The malignant portion is composed of medium-sized to large pleomorphic basaloid cells with numerous atypical mitotic figures and necrotic cells, presenting as confluent sheets and nodules with an infiltrative growth pattern (basal cell adenocarcinoma–like pattern, high grade).
Invasive adenocarcinoma NOS arising from pre-existing spiradenoma. This tumour shows highly atypical cells arranged in an alveolar pattern, with occasional lumina.
Several malignant patterns, including sarcomatoid carcinoma, in a pre-existing spiradenoma. Note the transition from the atypical basaloid component to a sarcomatoid component.
Several malignant patterns, including sarcomatoid carcinoma, in a pre-existing spiradenoma. Note the transition from the atypical basaloid component to a sarcomatoid component.
Malignant neoplasm arising in pre-existing spiradenoma. The transition between the benign parent lesion and the evolving malignant neoplasm.
Malignant neoplasm arising in pre-existing spiradenoma. Higher magnification shows that the low-grade malignant area is characterized by loss of the dual cell differentiation, mild to moderate cytological atypia with nuclear crowding, and mitotic activity.

Q: A deeply infiltrative skin tumor that typically presents as a sclerotic plaque and histologically displays strands and nests of bland epithelial cells embedded in a dense desmoplastic stroma is characteristic of [...].
Microcystic adnexal carcinoma. Deeply infiltrative tumour.
Microcystic adnexal carcinoma. Strands and nests of bland epithelial cells infiltrate the dermis and subcutis and are associated with desmoplasia.
A: Microcystic Adnexal Carcinoma
Back Extra: Microcystic Adnexal Carcinoma
- Clinical: Most cases arise as a sclerotic plaque, affecting primarily White populations in their fifth or sixth decade of life.
- Micro: Characterized by infiltrative nests and strands of bland epithelial cells, cornifying cysts, and ductal structures with perineural invasion.
- Ancillary: Immunohistochemical markers such as cytokeratins, p63, EMA, and CEA can help distinguish it from other adnexal carcinomas.
Reference Gallery:
Microcystic adnexal carcinoma. Deeply infiltrative tumour.
Microcystic adnexal carcinoma. Strands and nests of bland epithelial cells infiltrate the dermis and subcutis and are associated with desmoplasia.
Microcystic adnexal carcinoma. Nests of bland epithelial cells with a keratocyst.

Q: A hallmark histologic feature of Microcystic Adnexal Carcinoma is the presence of nests of bland epithelial cells containing small, keratin-filled spaces known as [...] (or keratocysts).
Microcystic adnexal carcinoma. Nests of bland epithelial cells with a keratocyst.
A: cornifying cysts
Back Extra: Microcystic Adnexal Carcinoma
- Clinical: Most cases arise as a sclerotic plaque, affecting primarily White populations in their fifth or sixth decade of life.
- Micro: Characterized by infiltrative nests and strands of bland epithelial cells, cornifying cysts, and ductal structures with perineural invasion.
- Ancillary: Immunohistochemical markers such as cytokeratins, p63, EMA, and CEA can help distinguish it from other adnexal carcinomas.
Reference Gallery:
Microcystic adnexal carcinoma. Deeply infiltrative tumour.
Microcystic adnexal carcinoma. Strands and nests of bland epithelial cells infiltrate the dermis and subcutis and are associated with desmoplasia.
Microcystic adnexal carcinoma. Nests of bland epithelial cells with a keratocyst.

Q: Histologically, Mucinous Carcinoma is characterized by neoplastic cells arranged in nests or strands floating in large lakes of [...].
Mucinous carcinoma. Neoplastic cells are arranged in nests, strands, or individual units floating in lakes of extracellular mucin, separated by variably thick fibrous septa. In this lesion, extracellular mucin constitutes > 90% (the pure type of mucinous carcinoma).
A: extracellular mucin
Back Extra: Mucinous Carcinoma
- Clinical: Mucinous carcinoma of the skin presents as a solitary, slow-growing nodule or cyst-like lesion that is flesh-coloured, blue, or erythematous, typically 15-20 mm in size.
- Micro: Neoplastic cells are arranged in nests, strands, or individual units floating in lakes of extracellular mucin, often with an in situ component.
- Ancillary: Staining for myoepithelial markers (p63, calponin) and epithelial markers (CK7, EMA, CEA) can help differentiate primary cutaneous mucinous carcinoma from metastatic lesions.
Reference Gallery:
Mucinous carcinoma. There is an invasive ductal component in addition to the mucinous component (the mixed type of mucinous carcinoma).
Mucinous carcinoma. An in situ component in mucinous carcinoma of the skin is a strong indicator of primary cutaneous origin; in situ lesions range from various types of ductal hyperplasia to ductal carcinoma in situ. The in situ component corresponds to ductal carcinoma in situ of micropapillary type.
Mucinous carcinoma. Neoplastic cells are arranged in nests, strands, or individual units floating in lakes of extracellular mucin, separated by variably thick fibrous septa. In this lesion, extracellular mucin constitutes > 90% (the pure type of mucinous carcinoma).
Mucinous carcinoma. An in situ component in mucinous carcinoma of the skin is a strong indicator of primary cutaneous origin; in situ lesions range from various types of ductal hyperplasia to ductal carcinoma in situ. Staining for calponin highlights preserved basal/myoepithelial cells in the ductal carcinoma in situ.

Q: When evaluating cutaneous Mucinous Carcinoma, finding an [...] (e.g., ductal carcinoma in situ) is a strong indicator of a primary cutaneous origin rather than a metastatic lesion.
Mucinous carcinoma. An in situ component in mucinous carcinoma of the skin is a strong indicator of primary cutaneous origin; in situ lesions range from various types of ductal hyperplasia to ductal carcinoma in situ. The in situ component corresponds to ductal carcinoma in situ of micropapillary type.
A: in situ component
Back Extra: Mucinous Carcinoma
- Clinical: Mucinous carcinoma of the skin presents as a solitary, slow-growing nodule or cyst-like lesion that is flesh-coloured, blue, or erythematous, typically 15-20 mm in size.
- Micro: Neoplastic cells are arranged in nests, strands, or individual units floating in lakes of extracellular mucin, often with an in situ component.
- Ancillary: Staining for myoepithelial markers (p63, calponin) and epithelial markers (CK7, EMA, CEA) can help differentiate primary cutaneous mucinous carcinoma from metastatic lesions.
Reference Gallery:
Mucinous carcinoma. There is an invasive ductal component in addition to the mucinous component (the mixed type of mucinous carcinoma).
Mucinous carcinoma. An in situ component in mucinous carcinoma of the skin is a strong indicator of primary cutaneous origin; in situ lesions range from various types of ductal hyperplasia to ductal carcinoma in situ. The in situ component corresponds to ductal carcinoma in situ of micropapillary type.
Mucinous carcinoma. Neoplastic cells are arranged in nests, strands, or individual units floating in lakes of extracellular mucin, separated by variably thick fibrous septa. In this lesion, extracellular mucin constitutes > 90% (the pure type of mucinous carcinoma).
Mucinous carcinoma. An in situ component in mucinous carcinoma of the skin is a strong indicator of primary cutaneous origin; in situ lesions range from various types of ductal hyperplasia to ductal carcinoma in situ. Staining for calponin highlights preserved basal/myoepithelial cells in the ductal carcinoma in situ.

Q: In cutaneous Mucinous Carcinoma, immunohistochemistry for myoepithelial markers such as [...] or p63 can highlight preserved basal cells to confirm an in situ component, helping to rule out metastasis.
Mucinous carcinoma. An in situ component in mucinous carcinoma of the skin is a strong indicator of primary cutaneous origin; in situ lesions range from various types of ductal hyperplasia to ductal carcinoma in situ. Staining for calponin highlights preserved basal/myoepithelial cells in the ductal carcinoma in situ.
A: calponin
Back Extra: Mucinous Carcinoma
- Clinical: Mucinous carcinoma of the skin presents as a solitary, slow-growing nodule or cyst-like lesion that is flesh-coloured, blue, or erythematous, typically 15-20 mm in size.
- Micro: Neoplastic cells are arranged in nests, strands, or individual units floating in lakes of extracellular mucin, often with an in situ component.
- Ancillary: Staining for myoepithelial markers (p63, calponin) and epithelial markers (CK7, EMA, CEA) can help differentiate primary cutaneous mucinous carcinoma from metastatic lesions.
Reference Gallery:
Mucinous carcinoma. There is an invasive ductal component in addition to the mucinous component (the mixed type of mucinous carcinoma).
Mucinous carcinoma. An in situ component in mucinous carcinoma of the skin is a strong indicator of primary cutaneous origin; in situ lesions range from various types of ductal hyperplasia to ductal carcinoma in situ. The in situ component corresponds to ductal carcinoma in situ of micropapillary type.
Mucinous carcinoma. Neoplastic cells are arranged in nests, strands, or individual units floating in lakes of extracellular mucin, separated by variably thick fibrous septa. In this lesion, extracellular mucin constitutes > 90% (the pure type of mucinous carcinoma).
Mucinous carcinoma. An in situ component in mucinous carcinoma of the skin is a strong indicator of primary cutaneous origin; in situ lesions range from various types of ductal hyperplasia to ductal carcinoma in situ. Staining for calponin highlights preserved basal/myoepithelial cells in the ductal carcinoma in situ.

Q: Microscopic examination of porocarcinoma reveals an invasive dermal proliferation of pleomorphic [...] cells with infiltrative borders and a prominent epidermal connection.
Porocarcinoma. An infiltrative neoplasm with a prominent epidermal connection.
Porocarcinoma. There is prominent infiltration of the dermis by strands and nests of poroid tumour cells.
Porocarcinoma. The tumour contains nests and strands of variable pleomorphic poroid cells connected to the epidermis.
A: poroid
Q: Porocarcinoma
- Clinical: Patients with [...] present with an ulcerated nodule, rapid growth, ulceration, and bleeding.
- Micro: Invasive [...] shows intradermal proliferation with infiltrative borders and atypical cytological features.
- Ancillary: [...] and EMA highlight ductal differentiation in porocarcinoma.
Reference Gallery:
Porocarcinoma. An infiltrative neoplasm with a prominent epidermal connection.
Porocarcinoma. There is prominent infiltration of the dermis by strands and nests of poroid tumour cells.
Porocarcinoma. The tumour contains nests and strands of variable pleomorphic poroid cells connected to the epidermis.
Porocarcinoma. CEA highlights ductal differentiation.
A: porocarcinoma; porocarcinoma; CEA

Q: Ductal differentiation in porocarcinoma can be highlighted using immunohistochemical stains for EMA and [...].
Porocarcinoma. CEA highlights ductal differentiation.
A: CEA
Q: Porocarcinoma
- Clinical: Patients with [...] present with an ulcerated nodule, rapid growth, ulceration, and bleeding.
- Micro: Invasive [...] shows intradermal proliferation with infiltrative borders and atypical cytological features.
- Ancillary: [...] and EMA highlight ductal differentiation in porocarcinoma.
Reference Gallery:
Porocarcinoma. An infiltrative neoplasm with a prominent epidermal connection.
Porocarcinoma. There is prominent infiltration of the dermis by strands and nests of poroid tumour cells.
Porocarcinoma. The tumour contains nests and strands of variable pleomorphic poroid cells connected to the epidermis.
Porocarcinoma. CEA highlights ductal differentiation.
A: porocarcinoma; porocarcinoma; CEA

Q: Histologically, a Poroma is characteristically composed of two distinct cell populations: poroid cells with scant cytoplasm, and [...] with ample eosinophilic cytoplasm.
Poroma. At high power, the neoplasm is composed of two populations of poroid and cuticular cells. Poroid cells have a rounded or oval nucleus and scant cytoplasm. Cuticular cells have ample eosinophilic cytoplasm and a central nucleus, sometimes with moderate atypia.
A: cuticular cells
Back Extra: Poroma
- Clinical: Poromas typically present as solitary, sessile or pedunculated papules or nodules, ranging from 2 to 20 mm in size, often with a reddish or flesh-colored appearance.
- Micro: Poromas are characterized by two populations of cells: poroid cells with scant cytoplasm and cuticular cells with ample eosinophilic cytoplasm.
- Ancillary: Most poromas harbor recurrent YAP1::MAML2 or YAP1::NUTM1 gene fusions.
Reference Gallery:
Poroma. A well-circumscribed neoplasm composed of basaloid cells and widely connected to the epidermis.
Poroma. At high power, the neoplasm is composed of two populations of poroid and cuticular cells. Poroid cells have a rounded or oval nucleus and scant cytoplasm. Cuticular cells have ample eosinophilic cytoplasm and a central nucleus, sometimes with moderate atypia.
Poroma. Dermoscopy shows a brown-red plaque with focal arborizing vessels.
Poroma. A darker, brown macular lesion with less distinct vessels by dermoscopy.
Poroma. Poroma forming a flesh-coloured nodule in an 88-year-old woman.

Q: A key architectural feature of Poroma is a well-circumscribed neoplasm composed of basaloid cells that is widely connected to the [...].
Poroma. A well-circumscribed neoplasm composed of basaloid cells and widely connected to the epidermis.
A: epidermis
Back Extra: Poroma
- Clinical: Poromas typically present as solitary, sessile or pedunculated papules or nodules, ranging from 2 to 20 mm in size, often with a reddish or flesh-colored appearance.
- Micro: Poromas are characterized by two populations of cells: poroid cells with scant cytoplasm and cuticular cells with ample eosinophilic cytoplasm.
- Ancillary: Most poromas harbor recurrent YAP1::MAML2 or YAP1::NUTM1 gene fusions.
Reference Gallery:
Poroma. A well-circumscribed neoplasm composed of basaloid cells and widely connected to the epidermis.
Poroma. At high power, the neoplasm is composed of two populations of poroid and cuticular cells. Poroid cells have a rounded or oval nucleus and scant cytoplasm. Cuticular cells have ample eosinophilic cytoplasm and a central nucleus, sometimes with moderate atypia.
Poroma. Dermoscopy shows a brown-red plaque with focal arborizing vessels.
Poroma. A darker, brown macular lesion with less distinct vessels by dermoscopy.
Poroma. Poroma forming a flesh-coloured nodule in an 88-year-old woman.

Q: Clinically, a Poroma often presents as a solitary, reddish or flesh-colored nodule; on dermoscopy, it frequently displays a brown-red plaque with focal [...] vessels.
Poroma. Dermoscopy shows a brown-red plaque with focal arborizing vessels.
Poroma. Poroma forming a flesh-coloured nodule in an 88-year-old woman.
A: arborizing
Back Extra: Poroma
- Clinical: Poromas typically present as solitary, sessile or pedunculated papules or nodules, ranging from 2 to 20 mm in size, often with a reddish or flesh-colored appearance.
- Micro: Poromas are characterized by two populations of cells: poroid cells with scant cytoplasm and cuticular cells with ample eosinophilic cytoplasm.
- Ancillary: Most poromas harbor recurrent YAP1::MAML2 or YAP1::NUTM1 gene fusions.
Reference Gallery:
Poroma. A well-circumscribed neoplasm composed of basaloid cells and widely connected to the epidermis.
Poroma. At high power, the neoplasm is composed of two populations of poroid and cuticular cells. Poroid cells have a rounded or oval nucleus and scant cytoplasm. Cuticular cells have ample eosinophilic cytoplasm and a central nucleus, sometimes with moderate atypia.
Poroma. Dermoscopy shows a brown-red plaque with focal arborizing vessels.
Poroma. A darker, brown macular lesion with less distinct vessels by dermoscopy.
Poroma. Poroma forming a flesh-coloured nodule in an 88-year-old woman.

Q: A skin tumor presenting as an intradermal circumscribed nodule composed of bland neoplastic cells in microcystic and tubular patterns with abundant luminal material, which characteristically harbors an ETV6::NTRK3 translocation, is [...].
Secretory carcinoma of the skin. The neoplasm usually occurs as an intradermal circumscribed nodule.
Secretory carcinoma of the skin. The neoplasm usually occurs as an intradermal circumscribed nodule.
Secretory carcinoma of the skin. The tumour is composed of bland neoplastic cells arranged in microcystic, tubular, and solid growth patterns, with characteristic abundant secretion within the microcystic and tubular spaces.
A: Secretory Carcinoma
Back Extra: Secretory Carcinoma
- Clinical: Secretory carcinoma presents as a nondescript solitary small papule or nodule, most commonly found in the axilla.
- Micro: The tumour is composed of bland neoplastic cells arranged in microcystic, tubular, and solid growth patterns, with characteristic abundant secretion within the microcystic and tubular spaces.
- Ancillary: ETV6::NTRK3 translocation is detected in most cases, and immunohistochemically, the neoplastic cells are diffusely positive for S100, mammaglobin, and STAT5A.
Reference Gallery:
Secretory carcinoma of the skin. The neoplasm usually occurs as an intradermal circumscribed nodule.
Secretory carcinoma of the skin. The neoplasm usually occurs as an intradermal circumscribed nodule.
Secretory carcinoma of the skin. The tumour is composed of bland neoplastic cells arranged in microcystic, tubular, and solid growth patterns, with characteristic abundant secretion within the microcystic and tubular spaces.

Q: On histologic examination of Secretory Carcinoma, the bland neoplastic cells are arranged in microcystic, tubular, and solid patterns with characteristic abundant [...] within the spaces.
Secretory carcinoma of the skin. The tumour is composed of bland neoplastic cells arranged in microcystic, tubular, and solid growth patterns, with characteristic abundant secretion within the microcystic and tubular spaces.
A: secretion
Back Extra: Secretory Carcinoma
- Clinical: Secretory carcinoma presents as a nondescript solitary small papule or nodule, most commonly found in the axilla.
- Micro: The tumour is composed of bland neoplastic cells arranged in microcystic, tubular, and solid growth patterns, with characteristic abundant secretion within the microcystic and tubular spaces.
- Ancillary: ETV6::NTRK3 translocation is detected in most cases, and immunohistochemically, the neoplastic cells are diffusely positive for S100, mammaglobin, and STAT5A.
Reference Gallery:
Secretory carcinoma of the skin. The neoplasm usually occurs as an intradermal circumscribed nodule.
Secretory carcinoma of the skin. The neoplasm usually occurs as an intradermal circumscribed nodule.
Secretory carcinoma of the skin. The tumour is composed of bland neoplastic cells arranged in microcystic, tubular, and solid growth patterns, with characteristic abundant secretion within the microcystic and tubular spaces.

Q: Histologically, the tumor cells of Signet-ring cell / histiocytoid carcinoma characteristically feature eccentric nuclei and [...] or eosinophilic granular cytoplasm.
Signet-ring cell / histiocytoid carcinoma. The tumour is composed of sheets of large so-called histiocytoid cells with abundant cytoplasm; some cells contain intracytoplasmic vacuoles.
A: vacuolated
Back Extra: Signet-ring cell / histiocytoid carcinoma
- Clinical: Patients with eyelid lesions present with a diffuse thickening of the involved lid, covered by normal or erythematous skin, often misinterpreted as inflammatory disorders.
- Micro: The tumour is composed of sheets or cords of cells with eccentric nuclei and vacuolated or eosinophilic granular cytoplasm.
- Ancillary: Somatic mutations in CDH1, PIK3CA, NTRK3, CDKN1B, and TP53 have been detected, but their diagnostic significance is still under investigation.
Reference Gallery:
Signet-ring cell / histiocytoid carcinoma. The neoplasm involves the whole dermis.
Signet-ring cell / histiocytoid carcinoma. The tumour is composed of sheets of large so-called histiocytoid cells with abundant cytoplasm; some cells contain intracytoplasmic vacuoles.

Q: At low power, a characteristic architectural feature of Signet-ring cell / histiocytoid carcinoma is diffuse neoplastic infiltration involving the entire [...].
Signet-ring cell / histiocytoid carcinoma. The neoplasm involves the whole dermis.
A: dermis
Back Extra: Signet-ring cell / histiocytoid carcinoma
- Clinical: Patients with eyelid lesions present with a diffuse thickening of the involved lid, covered by normal or erythematous skin, often misinterpreted as inflammatory disorders.
- Micro: The tumour is composed of sheets or cords of cells with eccentric nuclei and vacuolated or eosinophilic granular cytoplasm.
- Ancillary: Somatic mutations in CDH1, PIK3CA, NTRK3, CDKN1B, and TP53 have been detected, but their diagnostic significance is still under investigation.
Reference Gallery:
Signet-ring cell / histiocytoid carcinoma. The neoplasm involves the whole dermis.
Signet-ring cell / histiocytoid carcinoma. The tumour is composed of sheets of large so-called histiocytoid cells with abundant cytoplasm; some cells contain intracytoplasmic vacuoles.

Q: Histologically, Spiradenoma typically forms well-circumscribed neoplastic nodules containing basaloid cells, numerous ductal structures, and admixed [...].
Spiradenoma. A section showing two well-circumscribed neoplastic nodules.
Spiradenoma. Detail of the basaloid cells with admixed basement membrane material and numerous ductal structures.
A: basement membrane material
Back Extra: Spiradenoma
- Clinical: Spiradenomas are rare, benign neoplasms that usually appear in adulthood and can present as solitary subcutaneous nodules or multiple lesions. Pain is a common feature, though its cause is unknown.
- Micro: Histologically, spiradenomas are composed of two types of cells: light (clear) cells in the center and dark cells forming the peripheral layer. Ductal structures and basement membrane material are frequently seen.
- Ancillary: Immunohistochemistry shows intense expression of SOX10 and calponin, SMA, and p63 in myoepithelial cells. Germline CYLD mutations are present in syndromic cases, while ALPK1 and CYLD mutations are seen in sporadic cases.
Reference Gallery:
Spiradenoma. A section showing two well-circumscribed neoplastic nodules.
Spiradenoma. Detail of the basaloid cells with admixed basement membrane material and numerous ductal structures.

Q: Microscopically, the basaloid nodules of Spiradenoma are characteristically composed of a dual cell population: peripheral dark cells and central [...].
Spiradenoma. Detail of the basaloid cells with admixed basement membrane material and numerous ductal structures.
A: light (clear) cells
Back Extra: Spiradenoma
- Clinical: Spiradenomas are rare, benign neoplasms that usually appear in adulthood and can present as solitary subcutaneous nodules or multiple lesions. Pain is a common feature, though its cause is unknown.
- Micro: Histologically, spiradenomas are composed of two types of cells: light (clear) cells in the center and dark cells forming the peripheral layer. Ductal structures and basement membrane material are frequently seen.
- Ancillary: Immunohistochemistry shows intense expression of SOX10 and calponin, SMA, and p63 in myoepithelial cells. Germline CYLD mutations are present in syndromic cases, while ALPK1 and CYLD mutations are seen in sporadic cases.
Reference Gallery:
Spiradenoma. A section showing two well-circumscribed neoplastic nodules.
Spiradenoma. Detail of the basaloid cells with admixed basement membrane material and numerous ductal structures.

Q: Histologically, Syringofibroadenoma is characterized by anastomosing cords of ductal epithelial cells arranged in a distinctive [...] pattern within a loose, edematous stroma.
Syringofibroadenoma. The tumour consists of cords of epithelial cells in a fenestrated pattern and anastomosing with each other. The stroma is oedematous, with loose collagen.
Syringofibroadenoma. Detail of the cords of epithelial cells and the loose collagen making up the tumour.
A: fenestrated
Back Extra: Syringofibroadenoma
- Clinical: Syringofibroadenoma typically affects older patients, with an average age of 60 years. Lesions can be solitary or multiple, often presenting as small papules or plaques on the lower extremities.
- Micro: Histopathology reveals ductal epithelial hyperplasia in a fenestrated pattern, with cords of epithelium interconnected in a loose, myxoid stroma containing abundant mucin and a lymphoplasmacytic infiltrate.
- Ancillary: Immunohistochemical studies show the presence of CEA, EMA, and filaggrin in the lumina of the small ducts, with a cytokeratin expression pattern similar to the distal portion of the eccrine duct.
Reference Gallery:
Syringofibroadenoma. The tumour consists of cords of epithelial cells in a fenestrated pattern and anastomosing with each other. The stroma is oedematous, with loose collagen.
Syringofibroadenoma. Detail of the cords of epithelial cells and the loose collagen making up the tumour.

Q: A skin biopsy reveals thin, interconnecting epithelial cords in a lattice-like arrangement set within a loose, edematous stroma with delicate collagen. This classic morphology represents a [...].
Syringofibroadenoma. The tumour consists of cords of epithelial cells in a fenestrated pattern and anastomosing with each other. The stroma is oedematous, with loose collagen.
Syringofibroadenoma. Detail of the cords of epithelial cells and the loose collagen making up the tumour.
A: Syringofibroadenoma
Back Extra: Syringofibroadenoma
- Clinical: Syringofibroadenoma typically affects older patients, with an average age of 60 years. Lesions can be solitary or multiple, often presenting as small papules or plaques on the lower extremities.
- Micro: Histopathology reveals ductal epithelial hyperplasia in a fenestrated pattern, with cords of epithelium interconnected in a loose, myxoid stroma containing abundant mucin and a lymphoplasmacytic infiltrate.
- Ancillary: Immunohistochemical studies show the presence of CEA, EMA, and filaggrin in the lumina of the small ducts, with a cytokeratin expression pattern similar to the distal portion of the eccrine duct.
Reference Gallery:
Syringofibroadenoma. The tumour consists of cords of epithelial cells in a fenestrated pattern and anastomosing with each other. The stroma is oedematous, with loose collagen.
Syringofibroadenoma. Detail of the cords of epithelial cells and the loose collagen making up the tumour.

Q: Clinically, Syringoma often presents as skin-colored or slightly yellow smooth papules that are classically located on the [...].
Eruptive syringoma. Multiple small papules below the eyebrows and the eyes.
A: eyelids
Back Extra: Syringoma
- Clinical: Syringoma manifests as skin-coloured or slightly yellow smooth papules, often on the eyelids, and can appear in eruptions on the anterior chest wall and flexural areas.
- Micro: Syringomas are well-circumscribed lesions in the upper dermis, characterized by ducts, cords, and cysts lined by a double layer of cuboidal cells within a sclerotic stroma.
- Ancillary: Ancillary studies are not typically relevant for diagnosing syringomas.
Reference Gallery:
Syringoma. Multiple, regular cystic spaces embedded in a sclerotic stroma.
Syringoma. Cystic spaces lined by cuboidal epithelium.
Eruptive syringoma. Multiple small papules below the eyebrows and the eyes.
Eruptive syringoma. Multiple papules across the skin of the neck.

Q: Histologically, the characteristic upper dermal ducts and cysts of Syringoma are lined by a double layer of [...] cells embedded within a sclerotic stroma.
Syringoma. Multiple, regular cystic spaces embedded in a sclerotic stroma.
Syringoma. Cystic spaces lined by cuboidal epithelium.
A: cuboidal
Back Extra: Syringoma
- Clinical: Syringoma manifests as skin-coloured or slightly yellow smooth papules, often on the eyelids, and can appear in eruptions on the anterior chest wall and flexural areas.
- Micro: Syringomas are well-circumscribed lesions in the upper dermis, characterized by ducts, cords, and cysts lined by a double layer of cuboidal cells within a sclerotic stroma.
- Ancillary: Ancillary studies are not typically relevant for diagnosing syringomas.
Reference Gallery:
Syringoma. Multiple, regular cystic spaces embedded in a sclerotic stroma.
Syringoma. Cystic spaces lined by cuboidal epithelium.
Eruptive syringoma. Multiple small papules below the eyebrows and the eyes.
Eruptive syringoma. Multiple papules across the skin of the neck.

Q: A biopsy of small, skin-colored eyelid papules showing upper dermal ducts and cysts lined by a double layer of cuboidal cells within a sclerotic stroma is pathognomonic for [...].
Syringoma. Multiple, regular cystic spaces embedded in a sclerotic stroma.
Syringoma. Cystic spaces lined by cuboidal epithelium.
Eruptive syringoma. Multiple small papules below the eyebrows and the eyes.
A: Syringoma
Back Extra: Syringoma
- Clinical: Syringoma manifests as skin-coloured or slightly yellow smooth papules, often on the eyelids, and can appear in eruptions on the anterior chest wall and flexural areas.
- Micro: Syringomas are well-circumscribed lesions in the upper dermis, characterized by ducts, cords, and cysts lined by a double layer of cuboidal cells within a sclerotic stroma.
- Ancillary: Ancillary studies are not typically relevant for diagnosing syringomas.
Reference Gallery:
Syringoma. Multiple, regular cystic spaces embedded in a sclerotic stroma.
Syringoma. Cystic spaces lined by cuboidal epithelium.
Eruptive syringoma. Multiple small papules below the eyebrows and the eyes.
Eruptive syringoma. Multiple papules across the skin of the neck.

Q: Histologically, Melanocytic Matricoma is characterized by solid aggregates of basophilic matrical and supramatrical cells, often with abundant melanin surrounding characteristic aggregates of [...].
Melanocytic matricoma. Scanning magnification showing a well-circumscribed dermal nodule.
Melanocytic matricoma. Higher magnification showing solid aggregates of basophilic matrical and supramatrical cells, with scant cytoplasm, round nuclei, prominent nucleoli, and abundant melanin around aggregates of shadow cells.
A: shadow cells
Back Extra: Melanocytic Matricoma
- Clinical: Melanocytic matricoma appears as a solitary, pigmented, purple or brownish-black papule or nodule. It is rare, with only about 25 cases reported, predominantly in elderly men.
- Micro: The lesion is a well-circumscribed dermal nodule composed of solid aggregates of basophilic matrical and supramatrical cells with scant cytoplasm, round nuclei, prominent nucleoli, and frequent mitotic figures.
- Ancillary: The matrical cells express PHLDA1 and nuclear β-catenin, but not BerEP4. Intratumoural melanocytes express S100, HMB45 antigen (PMEL [gp100]), melan-A, and SOX10.
Reference Gallery:
Melanocytic matricoma. Scanning magnification showing a well-circumscribed dermal nodule.
Melanocytic matricoma. Higher magnification showing solid aggregates of basophilic matrical and supramatrical cells, with scant cytoplasm, round nuclei, prominent nucleoli, and abundant melanin around aggregates of shadow cells.

Q: Histologically, the characteristic architecture of Pilar sheath acanthoma consists of a large central [...] filled with basket-weave orthokeratotic keratin, surrounded by radiating solid lobules of pale eosinophilic cells.
Pilar sheath acanthoma. Scanning magnification showing a large central crater filled by basket-weave basophilic orthokeratotic keratin.
Pilar sheath acanthoma. Higher magnification showing solid lobules composed of pale eosinophilic cells similar to those seen in the outer root sheath of the isthmus of the hair follicle.
A: crater
Back Extra: Pilar sheath acanthoma
- Clinical: Pilar sheath acanthoma is a rare, benign neoplasm that typically presents as a single papule or nodule with a central depression filled with keratin, often diagnosed clinically as a giant comedo.
- Micro: Histologically, it consists of a large central crater filled with basket-weave orthokeratotic keratin and solid lobules of pale eosinophilic cells similar to the outer root sheath of the hair follicle.
- Ancillary: Ancillary studies are not typically required for diagnosis.
Reference Gallery:
Pilar sheath acanthoma. Scanning magnification showing a large central crater filled by basket-weave basophilic orthokeratotic keratin.
Pilar sheath acanthoma. Higher magnification showing solid lobules composed of pale eosinophilic cells similar to those seen in the outer root sheath of the isthmus of the hair follicle.

Q: In Pilar sheath acanthoma, the solid epithelial lobules radiating from the central invagination are composed of pale eosinophilic cells that microscopically resemble the [...] of the hair follicle.
Pilar sheath acanthoma. Higher magnification showing solid lobules composed of pale eosinophilic cells similar to those seen in the outer root sheath of the isthmus of the hair follicle.
A: outer root sheath
Back Extra: Pilar sheath acanthoma
- Clinical: Pilar sheath acanthoma is a rare, benign neoplasm that typically presents as a single papule or nodule with a central depression filled with keratin, often diagnosed clinically as a giant comedo.
- Micro: Histologically, it consists of a large central crater filled with basket-weave orthokeratotic keratin and solid lobules of pale eosinophilic cells similar to the outer root sheath of the hair follicle.
- Ancillary: Ancillary studies are not typically required for diagnosis.
Reference Gallery:
Pilar sheath acanthoma. Scanning magnification showing a large central crater filled by basket-weave basophilic orthokeratotic keratin.
Pilar sheath acanthoma. Higher magnification showing solid lobules composed of pale eosinophilic cells similar to those seen in the outer root sheath of the isthmus of the hair follicle.

Q: In Pilomatrical Carcinoma, the malignant adnexal tumor classically shows highly atypical, immature basaloid cells surrounding aggregates of anucleate [...].
Pilomatrical carcinoma. Higher magnification showing solid aggregates composed of matrical, intermediate, and shadow cells.
Pilomatrical carcinoma. Still higher magnification showing neoplastic matrical cells around aggregates of shadow cells.
A: shadow cells
Back Extra: Pilomatrical Carcinoma
- Clinical: Pilomatrical carcinoma is a rare, often ulcerated nodule, commonly found on the face in middle-aged or elderly individuals.
- Micro: The lesion is composed of solid aggregates of immature basaloid matrical cells with scant cytoplasm, a vesicular nucleus, and numerous mitoses, often with areas of necrosis.
- Ancillary: Immunohistochemistry shows nuclear and cytoplasmic staining for β-catenin in the basaloid matrical cells, and mutations in exon 3 of the CTNNB1 gene can be detected.
Reference Gallery:
Pilomatrical carcinoma. Scanning magnification showing a nodular lesion with large areas of necrosis.
Pilomatrical carcinoma. Higher magnification showing solid aggregates composed of matrical, intermediate, and shadow cells.
Pilomatrical carcinoma. Still higher magnification showing neoplastic matrical cells around aggregates of shadow cells.
Pilomatrical carcinoma. Clinical appearance of a lesion on the neck.

Q: At scanning magnification, Pilomatrical Carcinoma frequently presents as an asymmetrical, heavily cellular nodular lesion characterized by large areas of [...].
Pilomatrical carcinoma. Scanning magnification showing a nodular lesion with large areas of necrosis.
A: necrosis
Back Extra: Pilomatrical Carcinoma
- Clinical: Pilomatrical carcinoma is a rare, often ulcerated nodule, commonly found on the face in middle-aged or elderly individuals.
- Micro: The lesion is composed of solid aggregates of immature basaloid matrical cells with scant cytoplasm, a vesicular nucleus, and numerous mitoses, often with areas of necrosis.
- Ancillary: Immunohistochemistry shows nuclear and cytoplasmic staining for β-catenin in the basaloid matrical cells, and mutations in exon 3 of the CTNNB1 gene can be detected.
Reference Gallery:
Pilomatrical carcinoma. Scanning magnification showing a nodular lesion with large areas of necrosis.
Pilomatrical carcinoma. Higher magnification showing solid aggregates composed of matrical, intermediate, and shadow cells.
Pilomatrical carcinoma. Still higher magnification showing neoplastic matrical cells around aggregates of shadow cells.
Pilomatrical carcinoma. Clinical appearance of a lesion on the neck.

Q: Clinically, Pilomatrical Carcinoma often presents as an ulcerated nodule on the face or neck, composed histologically of solid aggregates of highly atypical, immature basaloid [...] cells with scant cytoplasm and numerous mitoses.
Pilomatrical carcinoma. Higher magnification showing solid aggregates composed of matrical, intermediate, and shadow cells.
Pilomatrical carcinoma. Clinical appearance of a lesion on the neck.
A: matrical
Back Extra: Pilomatrical Carcinoma
- Clinical: Pilomatrical carcinoma is a rare, often ulcerated nodule, commonly found on the face in middle-aged or elderly individuals.
- Micro: The lesion is composed of solid aggregates of immature basaloid matrical cells with scant cytoplasm, a vesicular nucleus, and numerous mitoses, often with areas of necrosis.
- Ancillary: Immunohistochemistry shows nuclear and cytoplasmic staining for β-catenin in the basaloid matrical cells, and mutations in exon 3 of the CTNNB1 gene can be detected.
Reference Gallery:
Pilomatrical carcinoma. Scanning magnification showing a nodular lesion with large areas of necrosis.
Pilomatrical carcinoma. Higher magnification showing solid aggregates composed of matrical, intermediate, and shadow cells.
Pilomatrical carcinoma. Still higher magnification showing neoplastic matrical cells around aggregates of shadow cells.
Pilomatrical carcinoma. Clinical appearance of a lesion on the neck.

Q: The classic microscopic finding in Pilomatricoma is a transition from basophilic matrical cells at the periphery to anucleate [...] cells.
Pilomatricoma. A well-circumscribed dermal nodule.
Pilomatricoma. Higher magnification showing transition from matrical cells at the periphery to intermediate and shadow cells.
A: shadow
Back Extra: Pilomatricoma
- Clinical: Pilomatricoma appears as a solitary, mobile, hard papule or nodule, often with areas of calcification.
- Micro: The tumor consists of well-circumscribed dermal nodules with a transition from matrical cells to shadow cells, often with calcification and ossification.
- Ancillary: Most pilomatricomas harbor activating mutations in the exon 3 of the β-catenin (CTNNB1) gene.
Reference Gallery:
Pilomatricoma. A well-circumscribed dermal nodule.
Pilomatricoma. Higher magnification showing transition from matrical cells at the periphery to intermediate and shadow cells.
Pilomatricoma. Macroscopic appearance (fixed specimen) with areas of keratinization.
Pilomatricoma. Pigmented nodule of the skin of the upper lip.

Q: A solitary, mobile, hard dermal nodule that exhibits macroscopic areas of keratinization and secondary calcification is characteristic of a [...].
Pilomatricoma. Macroscopic appearance (fixed specimen) with areas of keratinization.
Pilomatricoma. Pigmented nodule of the skin of the upper lip.
A: Pilomatricoma
Back Extra: Pilomatricoma
- Clinical: Pilomatricoma appears as a solitary, mobile, hard papule or nodule, often with areas of calcification.
- Micro: The tumor consists of well-circumscribed dermal nodules with a transition from matrical cells to shadow cells, often with calcification and ossification.
- Ancillary: Most pilomatricomas harbor activating mutations in the exon 3 of the β-catenin (CTNNB1) gene.
Reference Gallery:
Pilomatricoma. A well-circumscribed dermal nodule.
Pilomatricoma. Higher magnification showing transition from matrical cells at the periphery to intermediate and shadow cells.
Pilomatricoma. Macroscopic appearance (fixed specimen) with areas of keratinization.
Pilomatricoma. Pigmented nodule of the skin of the upper lip.

Q: Most cases of Pilomatricoma harbor an activating mutation in exon 3 of the [...] gene, which encodes $\beta$-catenin.
Pilomatricoma. Higher magnification showing transition from matrical cells at the periphery to intermediate and shadow cells.
A: CTNNB1
Back Extra: Pilomatricoma
- Clinical: Pilomatricoma appears as a solitary, mobile, hard papule or nodule, often with areas of calcification.
- Micro: The tumor consists of well-circumscribed dermal nodules with a transition from matrical cells to shadow cells, often with calcification and ossification.
- Ancillary: Most pilomatricomas harbor activating mutations in the exon 3 of the β-catenin (CTNNB1) gene.
Reference Gallery:
Pilomatricoma. A well-circumscribed dermal nodule.
Pilomatricoma. Higher magnification showing transition from matrical cells at the periphery to intermediate and shadow cells.
Pilomatricoma. Macroscopic appearance (fixed specimen) with areas of keratinization.
Pilomatricoma. Pigmented nodule of the skin of the upper lip.

Q: Proliferating trichilemmal tumor is characterized histologically by a large, well-circumscribed dermal nodule composed of neoplastic aggregates that undergo characteristic [...].
Proliferating trichilemmal tumour. Scanning magnification showing a large and well-circumscribed dermal nodule.
Proliferating trichilemmal tumour. Higher magnification showing trichilemmal keratinization in neoplastic aggregates.
A: trichilemmal keratinization
Back Extra: Proliferating trichilemmal tumour
- Clinical: Proliferating trichilemmal tumour (PTT) usually manifests as a solitary, slow-growing, exophytic lesion, 20–250 mm in size, most commonly on the scalp in women aged > 40 years.
- Micro: PTT displays a well-circumscribed dermal solid and cystic neoplasm with prominent epithelial infoldings into the cystic cavity, and trichilemmal keratinization.
- Ancillary: Aneuploidy has been demonstrated in some cases by flow cytometry, and TP53 mutations and loss of heterozygosity at 17p have been described in the malignant areas of PTT.
Reference Gallery:
Proliferating trichilemmal tumour. Scanning magnification showing a large and well-circumscribed dermal nodule.
Proliferating trichilemmal tumour. Higher magnification showing trichilemmal keratinization in neoplastic aggregates.

Q: The diagnosis of [...] is histologically characterized by a poorly circumscribed, infiltrative cutaneous lesion exhibiting central cystic areas, irregular nests of atypical clear cells, and stromal invasion.
Trichilemmal carcinoma. High-power view showing the vacuolated cytoplasm and the irregular shape of the nests, with stromal invasion.
Trichilemmal carcinoma. Low-power view showing a poorly circumscribed infiltrative lesion with a central cystic area.
A: Trichilemmal Carcinoma
Back Extra: Trichilemmal Carcinoma
- Clinical: Trichilemmal carcinoma often presents as an erythematous, tan, or flesh-coloured papule, a keratotic nodule, or an indurated plaque, frequently ulcerated, in sun-exposed areas such as the face, scalp, and neck.
- Micro: Characterized by large atypical cells with clear cytoplasm, prominent nucleoli, and foci of trichilemmal keratinization, with an invasive component and possible pagetoid spread in the overlying epidermis.
- Ancillary: Trichilemmal carcinoma expresses CK1, CK10, CK14, CK7, and CK17, and is strongly positive for p53 and focally positive for CD34 (My10), but usually negative for EMA.
Reference Gallery:
Trichilemmal carcinoma. High-power view showing the vacuolated cytoplasm and the irregular shape of the nests, with stromal invasion.
Trichilemmal carcinoma. Low-power view showing a poorly circumscribed infiltrative lesion with a central cystic area.

Q: At high power, the irregular, infiltrative nests of Trichilemmal Carcinoma are characteristically composed of large atypical cells with prominent nucleoli and abundant, [...] (vacuolated) cytoplasm.
Trichilemmal carcinoma. High-power view showing the vacuolated cytoplasm and the irregular shape of the nests, with stromal invasion.
A: clear
Back Extra: Trichilemmal Carcinoma
- Clinical: Trichilemmal carcinoma often presents as an erythematous, tan, or flesh-coloured papule, a keratotic nodule, or an indurated plaque, frequently ulcerated, in sun-exposed areas such as the face, scalp, and neck.
- Micro: Characterized by large atypical cells with clear cytoplasm, prominent nucleoli, and foci of trichilemmal keratinization, with an invasive component and possible pagetoid spread in the overlying epidermis.
- Ancillary: Trichilemmal carcinoma expresses CK1, CK10, CK14, CK7, and CK17, and is strongly positive for p53 and focally positive for CD34 (My10), but usually negative for EMA.
Reference Gallery:
Trichilemmal carcinoma. High-power view showing the vacuolated cytoplasm and the irregular shape of the nests, with stromal invasion.
Trichilemmal carcinoma. Low-power view showing a poorly circumscribed infiltrative lesion with a central cystic area.

Q: Histologically, Trichilemmoma shows bulbous thickening of the follicular infundibulum with peripheral palisading and a characteristically thick [...].
Trichilemmoma. Scanning magnification showing a lesion composed of bulbous thickening of the follicular infundibula.
Trichilemmoma. Higher magnification showing lobules of monomorphic epithelial cells with pale, eosinophilic, or clear cytoplasm. The cells in the periphery display palisading.
Trichilemmoma. Base of lesion showing peripheral palisading and the basement membrane.
A: basement membrane
Back Extra: Trichilemmoma
- Clinical: Trichilemmoma presents as a solitary, small (3–8 mm in diameter), hemispherical papule, often in middle-aged to elderly adults, and can be associated with Cowden syndrome.
- Micro: Histologically, trichilemmoma shows bulbous thickening of the follicular infundibulum with peripheral palisading and a thick basement membrane, and monomorphic epithelial cells with pale, eosinophilic, or clear cytoplasm.
- Ancillary: PTEN expression may be lost in trichilemmomas, particularly in those associated with Cowden syndrome, and HRAS activating mutations are common.
Reference Gallery:
Trichilemmoma. Scanning magnification showing a lesion composed of bulbous thickening of the follicular infundibula.
Trichilemmoma. Higher magnification showing lobules of monomorphic epithelial cells with pale, eosinophilic, or clear cytoplasm. The cells in the periphery display palisading.
Trichilemmoma. Base of lesion showing peripheral palisading and the basement membrane.
Trichilemmoma. Base of a lesion showing peripheral palisading and the basement membrane.
Multiple trichilemmomas in Cowden syndrome. Clinical appearance.

Q: The presence of multiple facial Trichilemmomas is a hallmark clinical sign of [...], frequently associated with loss of PTEN expression.
Multiple trichilemmomas in Cowden syndrome. Clinical appearance.
A: Cowden syndrome
Back Extra: Trichilemmoma
- Clinical: Trichilemmoma presents as a solitary, small (3–8 mm in diameter), hemispherical papule, often in middle-aged to elderly adults, and can be associated with Cowden syndrome.
- Micro: Histologically, trichilemmoma shows bulbous thickening of the follicular infundibulum with peripheral palisading and a thick basement membrane, and monomorphic epithelial cells with pale, eosinophilic, or clear cytoplasm.
- Ancillary: PTEN expression may be lost in trichilemmomas, particularly in those associated with Cowden syndrome, and HRAS activating mutations are common.
Reference Gallery:
Trichilemmoma. Scanning magnification showing a lesion composed of bulbous thickening of the follicular infundibula.
Trichilemmoma. Higher magnification showing lobules of monomorphic epithelial cells with pale, eosinophilic, or clear cytoplasm. The cells in the periphery display palisading.
Trichilemmoma. Base of lesion showing peripheral palisading and the basement membrane.
Trichilemmoma. Base of a lesion showing peripheral palisading and the basement membrane.
Multiple trichilemmomas in Cowden syndrome. Clinical appearance.

Q: Clinically, [...] often presents as a well-circumscribed, slowly growing solitary nodule, most commonly located on the face or scalp.
Trichoadenoma. A well-circumscribed nodule on the scalp of an elderly male patient.
A: Trichoadenoma
Back Extra: Trichoadenoma
- Clinical: Trichoadenoma usually appears as a small, slowly growing, solitary nodular lesion with a telangiectatic surface, commonly located on the face or scalp.
- Micro: Histologically, trichoadenoma is characterized by well-circumscribed dermal nodules with numerous infundibulocystic structures and a densely vascularized stroma.
- Ancillary: Immunohistochemistry shows scattered CK20-positive Merkel cells, supporting the differentiation towards the follicular infundibulum and outer root sheath.
Reference Gallery:
Trichoadenoma. A well-circumscribed nodule on the scalp of an elderly male patient.
Trichoadenoma. Low-power view showing multiple cystic structures involving the dermis.
Trichoadenoma. Multiple cystic structures involve the dermis.

Q: Histologically, Trichoadenoma is characterized by well-circumscribed dermal nodules containing numerous [...] structures within a densely vascularized stroma.
Trichoadenoma. Low-power view showing multiple cystic structures involving the dermis.
Trichoadenoma. Multiple cystic structures involve the dermis.
A: infundibulocystic
Back Extra: Trichoadenoma
- Clinical: Trichoadenoma usually appears as a small, slowly growing, solitary nodular lesion with a telangiectatic surface, commonly located on the face or scalp.
- Micro: Histologically, trichoadenoma is characterized by well-circumscribed dermal nodules with numerous infundibulocystic structures and a densely vascularized stroma.
- Ancillary: Immunohistochemistry shows scattered CK20-positive Merkel cells, supporting the differentiation towards the follicular infundibulum and outer root sheath.
Reference Gallery:
Trichoadenoma. A well-circumscribed nodule on the scalp of an elderly male patient.
Trichoadenoma. Low-power view showing multiple cystic structures involving the dermis.
Trichoadenoma. Multiple cystic structures involve the dermis.

Q: Microscopic examination of Trichoblastic Carcinoma/Carcinosarcoma reveals an atypical basaloid epithelial component intimately associated with a distinct stromal component that recapitulates [...].
Trichoblastic carcinoma. This entity resembles a trichoblastoma due to its epithelial basaloid (follicular germinative) cell nodules associated with abundant specific follicular stroma, but unlike in trichoblastoma, there is cellular atypia in the epithelial component and atypical mitotic figures.
Trichoblastic carcinosarcoma. The epithelial component is composed of basaloid cells resembling those seen in conventional basal cell carcinoma but showing nuclear crowding, abnormal mitotic figures, and necrosis. Germ-like structures are present focally. The epithelial component is intimately associated with the stroma, which recapitulates specific follicular mesenchyme by virtue of its papilla-like aggregations but is composed of clearly atypical cells with numerous abnormal mitotic figures, crowding, and hyperchromasia.
A: follicular mesenchyme
Back Extra: Trichoblastic Carcinoma/Carcinosarcoma
- Clinical: Trichoblastic carcinoma/carcinosarcoma affects elderly patients and typically presents as a solitary nodule, often with an ulcerated surface.
- Micro: The epithelial component of trichoblastic carcinoma/carcinosarcoma shows severe atypia, abnormal mitotic figures, and necrosis, closely associated with a stromal component that recapitulates specific follicular mesenchyme.
- Ancillary: Genetic variants such as CDKN2A, TP53, TERT promoter, CTNNB1, and SUFU have been described in trichoblastic carcinosarcoma, but diagnostic molecular pathology is not essential for diagnosis.
Reference Gallery:
Trichoblastic carcinoma. This entity resembles a trichoblastoma due to its epithelial basaloid (follicular germinative) cell nodules associated with abundant specific follicular stroma, but unlike in trichoblastoma, there is cellular atypia in the epithelial component and atypical mitotic figures.
Trichoblastic carcinosarcoma. The epithelial component is composed of basaloid cells resembling those seen in conventional basal cell carcinoma but showing nuclear crowding, abnormal mitotic figures, and necrosis. Germ-like structures are present focally. The epithelial component is intimately associated with the stroma, which recapitulates specific follicular mesenchyme by virtue of its papilla-like aggregations but is composed of clearly atypical cells with numerous abnormal mitotic figures, crowding, and hyperchromasia.
Trichoblastic carcinosarcoma. The tumour is composed of epithelial and stromal components with distinctive appearances.
Trichoblastic carcinoma. A large ulcerated nodule shown to be a trichoblastic carcinoma by histology.
High-grade trichoblastic carcinoma. Low-power examination shows a dermal malignant neoplasm in association with a residuum of benign trichoblastoma, with a detectable zone of transformation.
High-grade trichoblastic carcinoma. The superficial portion of the biphasic tumour shows small nodular aggregations of follicular germinative cells and small infundibulocystic structures.
High-grade trichoblastic carcinoma. The deeper large neoplastic aggregates demonstrate comedo-like necrosis and are composed of basaloid cells with severe cytological atypia. Note the presence of numerous atypical mitoses.

Q: High-grade Trichoblastic Carcinoma/Carcinosarcoma is characterized by deep neoplastic aggregates of atypical basaloid cells that frequently exhibit central [...].
High-grade trichoblastic carcinoma. The deeper large neoplastic aggregates demonstrate comedo-like necrosis and are composed of basaloid cells with severe cytological atypia. Note the presence of numerous atypical mitoses.
A: comedo-like necrosis
Back Extra: Trichoblastic Carcinoma/Carcinosarcoma
- Clinical: Trichoblastic carcinoma/carcinosarcoma affects elderly patients and typically presents as a solitary nodule, often with an ulcerated surface.
- Micro: The epithelial component of trichoblastic carcinoma/carcinosarcoma shows severe atypia, abnormal mitotic figures, and necrosis, closely associated with a stromal component that recapitulates specific follicular mesenchyme.
- Ancillary: Genetic variants such as CDKN2A, TP53, TERT promoter, CTNNB1, and SUFU have been described in trichoblastic carcinosarcoma, but diagnostic molecular pathology is not essential for diagnosis.
Reference Gallery:
Trichoblastic carcinoma. This entity resembles a trichoblastoma due to its epithelial basaloid (follicular germinative) cell nodules associated with abundant specific follicular stroma, but unlike in trichoblastoma, there is cellular atypia in the epithelial component and atypical mitotic figures.
Trichoblastic carcinosarcoma. The epithelial component is composed of basaloid cells resembling those seen in conventional basal cell carcinoma but showing nuclear crowding, abnormal mitotic figures, and necrosis. Germ-like structures are present focally. The epithelial component is intimately associated with the stroma, which recapitulates specific follicular mesenchyme by virtue of its papilla-like aggregations but is composed of clearly atypical cells with numerous abnormal mitotic figures, crowding, and hyperchromasia.
Trichoblastic carcinosarcoma. The tumour is composed of epithelial and stromal components with distinctive appearances.
Trichoblastic carcinoma. A large ulcerated nodule shown to be a trichoblastic carcinoma by histology.
High-grade trichoblastic carcinoma. Low-power examination shows a dermal malignant neoplasm in association with a residuum of benign trichoblastoma, with a detectable zone of transformation.
High-grade trichoblastic carcinoma. The superficial portion of the biphasic tumour shows small nodular aggregations of follicular germinative cells and small infundibulocystic structures.
High-grade trichoblastic carcinoma. The deeper large neoplastic aggregates demonstrate comedo-like necrosis and are composed of basaloid cells with severe cytological atypia. Note the presence of numerous atypical mitoses.

Q: A defining histologic feature in some cases of Trichoblastic Carcinoma/Carcinosarcoma is the presence of a detectable zone of transformation arising from a benign precursor residuum, specifically a pre-existing [...].
High-grade trichoblastic carcinoma. Low-power examination shows a dermal malignant neoplasm in association with a residuum of benign trichoblastoma, with a detectable zone of transformation.
A: trichoblastoma
Back Extra: Trichoblastic Carcinoma/Carcinosarcoma
- Clinical: Trichoblastic carcinoma/carcinosarcoma affects elderly patients and typically presents as a solitary nodule, often with an ulcerated surface.
- Micro: The epithelial component of trichoblastic carcinoma/carcinosarcoma shows severe atypia, abnormal mitotic figures, and necrosis, closely associated with a stromal component that recapitulates specific follicular mesenchyme.
- Ancillary: Genetic variants such as CDKN2A, TP53, TERT promoter, CTNNB1, and SUFU have been described in trichoblastic carcinosarcoma, but diagnostic molecular pathology is not essential for diagnosis.
Reference Gallery:
Trichoblastic carcinoma. This entity resembles a trichoblastoma due to its epithelial basaloid (follicular germinative) cell nodules associated with abundant specific follicular stroma, but unlike in trichoblastoma, there is cellular atypia in the epithelial component and atypical mitotic figures.
Trichoblastic carcinosarcoma. The epithelial component is composed of basaloid cells resembling those seen in conventional basal cell carcinoma but showing nuclear crowding, abnormal mitotic figures, and necrosis. Germ-like structures are present focally. The epithelial component is intimately associated with the stroma, which recapitulates specific follicular mesenchyme by virtue of its papilla-like aggregations but is composed of clearly atypical cells with numerous abnormal mitotic figures, crowding, and hyperchromasia.
Trichoblastic carcinosarcoma. The tumour is composed of epithelial and stromal components with distinctive appearances.
Trichoblastic carcinoma. A large ulcerated nodule shown to be a trichoblastic carcinoma by histology.
High-grade trichoblastic carcinoma. Low-power examination shows a dermal malignant neoplasm in association with a residuum of benign trichoblastoma, with a detectable zone of transformation.
High-grade trichoblastic carcinoma. The superficial portion of the biphasic tumour shows small nodular aggregations of follicular germinative cells and small infundibulocystic structures.
High-grade trichoblastic carcinoma. The deeper large neoplastic aggregates demonstrate comedo-like necrosis and are composed of basaloid cells with severe cytological atypia. Note the presence of numerous atypical mitoses.

Q: Clinically, a Trichofolliculoma typically presents as a skin-colored, dome-shaped papule with a central pore containing thin white vellus hair shafts; this specific clinical presentation is known as the [...].
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
A: Pinkus sign
Back Extra: Trichofolliculoma
- Clinical: Trichofolliculoma presents as a single, skin-colored, dome-shaped papule, typically 5-7 mm in diameter, often with a central pore containing thin white vellus hair shafts (Pinkus sign).
- Micro: Histologically, trichofolliculoma is characterized by a central dilated follicular infundibulum with numerous vellus hair follicles radiating from it, showing differentiation towards the lower follicle segment.
- Ancillary: Signalling pathways involving BMPs and PYGO2 are associated with the experimental development of trichofolliculoma-like proliferations.
Reference Gallery:
Trichofolliculoma. Scanning magnification showing a symmetrical, well-circumscribed dermal lesion with a central, dilated, follicular infundibulum connected with the epidermis.
Trichofolliculoma. Higher magnification showing numerous villous hair follicles, with differentiation towards the lower hair follicle segment in different stages of development, emanating radially from the central cystic infundibulum.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Folliculocystic sebaceous hamartoma (so-called sebaceous trichofolliculoma). Well-developed, large lobules with mature sebocytes are observed.

Q: Histologically, a Trichofolliculoma is characterized by numerous vellus hair follicles radiating outward from a central, dilated [...].
Trichofolliculoma. Scanning magnification showing a symmetrical, well-circumscribed dermal lesion with a central, dilated, follicular infundibulum connected with the epidermis.
Trichofolliculoma. Higher magnification showing numerous villous hair follicles, with differentiation towards the lower hair follicle segment in different stages of development, emanating radially from the central cystic infundibulum.
A: follicular infundibulum
Back Extra: Trichofolliculoma
- Clinical: Trichofolliculoma presents as a single, skin-colored, dome-shaped papule, typically 5-7 mm in diameter, often with a central pore containing thin white vellus hair shafts (Pinkus sign).
- Micro: Histologically, trichofolliculoma is characterized by a central dilated follicular infundibulum with numerous vellus hair follicles radiating from it, showing differentiation towards the lower follicle segment.
- Ancillary: Signalling pathways involving BMPs and PYGO2 are associated with the experimental development of trichofolliculoma-like proliferations.
Reference Gallery:
Trichofolliculoma. Scanning magnification showing a symmetrical, well-circumscribed dermal lesion with a central, dilated, follicular infundibulum connected with the epidermis.
Trichofolliculoma. Higher magnification showing numerous villous hair follicles, with differentiation towards the lower hair follicle segment in different stages of development, emanating radially from the central cystic infundibulum.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Folliculocystic sebaceous hamartoma (so-called sebaceous trichofolliculoma). Well-developed, large lobules with mature sebocytes are observed.

Q: A sebaceous Trichofolliculoma is characterized by the presence of well-developed lobules with mature sebocytes radiating from the center and is alternatively termed a [...].
Folliculocystic sebaceous hamartoma (so-called sebaceous trichofolliculoma). Well-developed, large lobules with mature sebocytes are observed.
A: folliculocystic sebaceous hamartoma
Back Extra: Trichofolliculoma
- Clinical: Trichofolliculoma presents as a single, skin-colored, dome-shaped papule, typically 5-7 mm in diameter, often with a central pore containing thin white vellus hair shafts (Pinkus sign).
- Micro: Histologically, trichofolliculoma is characterized by a central dilated follicular infundibulum with numerous vellus hair follicles radiating from it, showing differentiation towards the lower follicle segment.
- Ancillary: Signalling pathways involving BMPs and PYGO2 are associated with the experimental development of trichofolliculoma-like proliferations.
Reference Gallery:
Trichofolliculoma. Scanning magnification showing a symmetrical, well-circumscribed dermal lesion with a central, dilated, follicular infundibulum connected with the epidermis.
Trichofolliculoma. Higher magnification showing numerous villous hair follicles, with differentiation towards the lower hair follicle segment in different stages of development, emanating radially from the central cystic infundibulum.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Trichofolliculoma. Dome-shape papule with vellus hair in a lower eyelid.
Folliculocystic sebaceous hamartoma (so-called sebaceous trichofolliculoma). Well-developed, large lobules with mature sebocytes are observed.

Q: A histological section of a cutaneous neoplasm shows anastomosing, horizontally arranged cords of epithelial cells with pale cytoplasm that connect to the epidermis, creating a fenestrated pattern. This is highly characteristic of a [...].
Tumour of follicular infundibulum. Scanning magnification showing a neoplasm composed of anastomosing horizontally arranged cords of epithelial cells, connecting at intervals with the epidermis and creating a fenestrated pattern.
Tumour of follicular infundibulum. Higher magnification showing most cells within the cords are large, with pale cytoplasm and a small round or oval nucleus. Small ductal structures are seen in the epithelial cords.
A: tumor of the follicular infundibulum
Back Extra: Tumour of the follicular infundibulum
- Clinical: Tumours of the follicular infundibulum typically present as multiple, smooth or slightly hyperkeratotic, hypopigmented papules, often in photoexposed areas.
- Micro: Histologically, the tumour is characterized by anastomosing cords of epithelial cells with pale cytoplasm and small round or oval nuclei, creating a fenestrated pattern.
- Ancillary: Ancillary studies are not typically required for diagnosis.
Reference Gallery:
Tumour of follicular infundibulum. Scanning magnification showing a neoplasm composed of anastomosing horizontally arranged cords of epithelial cells, connecting at intervals with the epidermis and creating a fenestrated pattern.
Tumour of follicular infundibulum. Higher magnification showing most cells within the cords are large, with pale cytoplasm and a small round or oval nucleus. Small ductal structures are seen in the epithelial cords.

Q: Histologically, a tumor of the follicular infundibulum is characterized by an anastomosing network of epithelial cords that connect to the epidermis, creating a distinct [...] pattern.
Tumour of follicular infundibulum. Scanning magnification showing a neoplasm composed of anastomosing horizontally arranged cords of epithelial cells, connecting at intervals with the epidermis and creating a fenestrated pattern.
A: fenestrated
Back Extra: Tumour of the follicular infundibulum
- Clinical: Tumours of the follicular infundibulum typically present as multiple, smooth or slightly hyperkeratotic, hypopigmented papules, often in photoexposed areas.
- Micro: Histologically, the tumour is characterized by anastomosing cords of epithelial cells with pale cytoplasm and small round or oval nuclei, creating a fenestrated pattern.
- Ancillary: Ancillary studies are not typically required for diagnosis.
Reference Gallery:
Tumour of follicular infundibulum. Scanning magnification showing a neoplasm composed of anastomosing horizontally arranged cords of epithelial cells, connecting at intervals with the epidermis and creating a fenestrated pattern.
Tumour of follicular infundibulum. Higher magnification showing most cells within the cords are large, with pale cytoplasm and a small round or oval nucleus. Small ductal structures are seen in the epithelial cords.

Q: A distinctive exophytic variant of Cutaneous Myoepithelioma is the [...] subtype, which is characterized by a sheet-like growth pattern of histiocytoid to short spindle cells with abundant pale eosinophilic cytoplasm.
Cutaneous syncytial myoepithelioma. This distinctive, often exophytic subtype shows a sheet-like growth pattern; note the adipocytic metaplasia in the deep aspect of the tumour.
Cutaneous syncytial myoepithelioma. The histiocytoid to short spindle cells contain abundant, pale eosinophilic, syncytial cytoplasm.
A: syncytial
Back Extra: Cutaneous Myoepithelioma
- Clinical: Patients with cutaneous myoepithelioma present with a painless, slow-growing papule or nodule, usually arising in adults with a peak incidence in the third through fifth decades and an M:F ratio of 3:1.
- Micro: Cutaneous myoepitheliomas are well-circumscribed, often showing a trabecular or nested arrangement of epithelioid, spindled, plasmacytoid, or clear cells, usually within a myxoid or hyalinized stroma.
- Ancillary: Cutaneous myoepitheliomas are consistently positive for EMA and S100. EWSR1 rearrangements can be detected in more than 80% of syncytial myoepitheliomas.
Reference Gallery:
Cutaneous syncytial myoepithelioma. This distinctive, often exophytic subtype shows a sheet-like growth pattern; note the adipocytic metaplasia in the deep aspect of the tumour.
Cutaneous syncytial myoepithelioma. The tumour shows an irregular interface with the dermis.
Cutaneous syncytial myoepithelioma. The histiocytoid to short spindle cells contain abundant, pale eosinophilic, syncytial cytoplasm.
Cutaneous myoepithelioma. The tumour is composed of uniform epithelioid cells showing a trabecular and nested growth pattern, within a prominent myxoid stroma.

Q: Classic Cutaneous Myoepithelioma typically presents as a well-circumscribed tumor composed of uniform epithelioid cells in a trabecular or nested arrangement, frequently embedded within a prominent [...] or hyalinized stroma.
Cutaneous myoepithelioma. The tumour is composed of uniform epithelioid cells showing a trabecular and nested growth pattern, within a prominent myxoid stroma.
A: myxoid
Back Extra: Cutaneous Myoepithelioma
- Clinical: Patients with cutaneous myoepithelioma present with a painless, slow-growing papule or nodule, usually arising in adults with a peak incidence in the third through fifth decades and an M:F ratio of 3:1.
- Micro: Cutaneous myoepitheliomas are well-circumscribed, often showing a trabecular or nested arrangement of epithelioid, spindled, plasmacytoid, or clear cells, usually within a myxoid or hyalinized stroma.
- Ancillary: Cutaneous myoepitheliomas are consistently positive for EMA and S100. EWSR1 rearrangements can be detected in more than 80% of syncytial myoepitheliomas.
Reference Gallery:
Cutaneous syncytial myoepithelioma. This distinctive, often exophytic subtype shows a sheet-like growth pattern; note the adipocytic metaplasia in the deep aspect of the tumour.
Cutaneous syncytial myoepithelioma. The tumour shows an irregular interface with the dermis.
Cutaneous syncytial myoepithelioma. The histiocytoid to short spindle cells contain abundant, pale eosinophilic, syncytial cytoplasm.
Cutaneous myoepithelioma. The tumour is composed of uniform epithelioid cells showing a trabecular and nested growth pattern, within a prominent myxoid stroma.

Q: Clinically, Onychocytic Matricoma typically presents as [...], which is characterized by a hyperpigmented streak and thickening of the nail plate.
Onychocytic matricoma. The fourth toenail unit demonstrates longitudinal pachymelanonychia.
A: longitudinal pachymelanonychia
Back Extra: Onychocytic Matricoma
- Clinical: Onychocytic matricoma typically presents as longitudinal pachymelanonychia, with a hyperpigmented streak and thickening of the nail plate.
- Micro: Histologically, the acanthotic pattern shows acanthosis of the matrix epithelium and whorls of epithelium with differentiation into onychocytes.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of onychocytic matricoma.
Reference Gallery:
Onychocytic matricoma. The acanthotic pattern of onychocytic matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation towards onychocytes.
Onychocytic matricoma. The acanthotic pattern of onychocytic matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation towards onychocytes.
Onychocytic matricoma. The acanthotic pattern of onychocytic matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation towards onychocytes.
Onychocytic matricoma. The fourth toenail unit demonstrates longitudinal pachymelanonychia.

Q: Histologically, the acanthotic pattern of Onychocytic Matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation into [...].
Onychocytic matricoma. The acanthotic pattern of onychocytic matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation towards onychocytes.
Onychocytic matricoma. The acanthotic pattern of onychocytic matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation towards onychocytes.
Onychocytic matricoma. The acanthotic pattern of onychocytic matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation towards onychocytes.
A: onychocytes
Back Extra: Onychocytic Matricoma
- Clinical: Onychocytic matricoma typically presents as longitudinal pachymelanonychia, with a hyperpigmented streak and thickening of the nail plate.
- Micro: Histologically, the acanthotic pattern shows acanthosis of the matrix epithelium and whorls of epithelium with differentiation into onychocytes.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of onychocytic matricoma.
Reference Gallery:
Onychocytic matricoma. The acanthotic pattern of onychocytic matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation towards onychocytes.
Onychocytic matricoma. The acanthotic pattern of onychocytic matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation towards onychocytes.
Onychocytic matricoma. The acanthotic pattern of onychocytic matricoma demonstrates acanthosis of the matrix epithelium and whorls of epithelium with differentiation towards onychocytes.
Onychocytic matricoma. The fourth toenail unit demonstrates longitudinal pachymelanonychia.

Q: Clinically, Onychomatricoma often presents as a proximal nodule with a thickened, yellowish nail plate, transverse overcurvature, and characteristic [...] visible at the distal free edge.
Onychomatricoma. Proximal nodule of the nail matrix, with thickened yellowish nail plate (xanthopachyonychia).
Onychomatricoma. Overcurvature and splinter haemorrhage.
Onychomatricoma. Cavities can be seen in the distal nail plate.
A: cavities
Back Extra: Onychomatricoma
- Clinical: Onychomatricoma presents as a nodular area under the proximal nail fold, with a thickened, yellowish nail plate and transverse overcurvature.
- Micro: The microscopic hallmark of onychomatricoma is the reduplicated matrical epithelium forming multiple V-shaped keratogenous zones over a hypercellular stroma.
- Ancillary: CD34-positive spindle cells are a characteristic feature in the stroma of onychomatricoma.
Reference Gallery:
Onychomatricoma. Proximal nodule of the nail matrix, with thickened yellowish nail plate (xanthopachyonychia).
Onychomatricoma. Overcurvature and splinter haemorrhage.
Onychomatricoma. Cavities can be seen in the distal nail plate.
Onychomatricoma. Longitudinal excision demonstrating the proximal fibroepithelial component in this case originating from the dorsal matrix, as well as thickened, interdigitating nail plate.
Onychomatricoma. Reduplicated matrical epithelium forming multiple V-shaped keratogenous zones, over a hypercellular stroma.
Onychomatricoma. Reduplicated matrical epithelium forming multiple V-shaped keratogenous zones, over a hypercellular stroma.
Onychomatricoma. Nail plate with thickening, loculated serum, and haemorrhage.
Onychomatricoma, pleomorphic pattern. Features similar to those of the classic pattern, with multinucleate and pleomorphic fibroblast-like cells in the stroma.
Onychomatricoma, pleomorphic pattern. Features similar to those of the classic pattern, with multinucleate and pleomorphic fibroblast-like cells in the stroma.
Onychomatricoma, proliferative pattern. Exaggerated matrical epithelium containing some incipient nail plate.
Onychomatricoma, proliferative pattern. Keratin whorls within nail plate, demonstrating other classic features in detached nail plate including multiple V-shaped invaginations of the superficial keratogenous zone proximally.

Q: The microscopic hallmark of Onychomatricoma consists of a hypercellular stroma overlaid by reduplicated matrical epithelium that forms multiple [...] keratogenous zones.
Onychomatricoma. Reduplicated matrical epithelium forming multiple V-shaped keratogenous zones, over a hypercellular stroma.
Onychomatricoma. Reduplicated matrical epithelium forming multiple V-shaped keratogenous zones, over a hypercellular stroma.
A: V-shaped
Back Extra: Onychomatricoma
- Clinical: Onychomatricoma presents as a nodular area under the proximal nail fold, with a thickened, yellowish nail plate and transverse overcurvature.
- Micro: The microscopic hallmark of onychomatricoma is the reduplicated matrical epithelium forming multiple V-shaped keratogenous zones over a hypercellular stroma.
- Ancillary: CD34-positive spindle cells are a characteristic feature in the stroma of onychomatricoma.
Reference Gallery:
Onychomatricoma. Proximal nodule of the nail matrix, with thickened yellowish nail plate (xanthopachyonychia).
Onychomatricoma. Overcurvature and splinter haemorrhage.
Onychomatricoma. Cavities can be seen in the distal nail plate.
Onychomatricoma. Longitudinal excision demonstrating the proximal fibroepithelial component in this case originating from the dorsal matrix, as well as thickened, interdigitating nail plate.
Onychomatricoma. Reduplicated matrical epithelium forming multiple V-shaped keratogenous zones, over a hypercellular stroma.
Onychomatricoma. Reduplicated matrical epithelium forming multiple V-shaped keratogenous zones, over a hypercellular stroma.
Onychomatricoma. Nail plate with thickening, loculated serum, and haemorrhage.
Onychomatricoma, pleomorphic pattern. Features similar to those of the classic pattern, with multinucleate and pleomorphic fibroblast-like cells in the stroma.
Onychomatricoma, pleomorphic pattern. Features similar to those of the classic pattern, with multinucleate and pleomorphic fibroblast-like cells in the stroma.
Onychomatricoma, proliferative pattern. Exaggerated matrical epithelium containing some incipient nail plate.
Onychomatricoma, proliferative pattern. Keratin whorls within nail plate, demonstrating other classic features in detached nail plate including multiple V-shaped invaginations of the superficial keratogenous zone proximally.

Q: Clinically, Onychopapilloma classically presents with [...] and a distal subungual hyperkeratotic spicule.
Onychopapilloma. Longitudinal erythronychia originating at distal nail matrix/lunula, with distal subungual hyperkeratotic nail spicule.
Onychopapilloma. Longitudinal erythronychia originating at distal nail matrix/lunula, with splinter haemorrhage.
A: longitudinal erythronychia
Back Extra: Onychopapilloma
- Clinical: Onychopapilloma typically presents with longitudinal erythronychia and distal subungual hyperkeratosis, often forming a spicule.
- Micro: Proximal nail bed may show matrical metaplasia, with multinucleate keratinocytes and hypergranulosis in the distal nail bed.
- Ancillary: No specific ancillary studies are typically required for the diagnosis of onychopapilloma.
Reference Gallery:
Onychopapilloma. Longitudinal erythronychia originating at distal nail matrix/lunula, with distal subungual hyperkeratotic nail spicule.
Onychopapilloma. Longitudinal erythronychia originating at distal nail matrix/lunula, with splinter haemorrhage.
Onychopapilloma. Longitudinal excision with hyperplasia of nail bed and distal hyperkeratosis forming a spicule.
Onychopapilloma. Proximal matrical metaplasia of nail bed.
Onychopapilloma. Multinucleate nail bed keratinocytes.
Onychopapilloma. Distal nail bed digitation with hypergranulosis, reminiscent of verruca, and distal subungual parakeratosis/hyperkeratosis.
Onychopapilloma. The distal nail bed shows hypergranulosis, distal subungual parakeratosis/hyperkeratosis, and loculated haemorrhage.

Q: On microscopic examination, the proximal nail bed of an Onychopapilloma classically shows [...] along with multinucleated keratinocytes.
Onychopapilloma. Proximal matrical metaplasia of nail bed.
Onychopapilloma. Multinucleate nail bed keratinocytes.
A: matrical metaplasia
Back Extra: Onychopapilloma
- Clinical: Onychopapilloma typically presents with longitudinal erythronychia and distal subungual hyperkeratosis, often forming a spicule.
- Micro: Proximal nail bed may show matrical metaplasia, with multinucleate keratinocytes and hypergranulosis in the distal nail bed.
- Ancillary: No specific ancillary studies are typically required for the diagnosis of onychopapilloma.
Reference Gallery:
Onychopapilloma. Longitudinal erythronychia originating at distal nail matrix/lunula, with distal subungual hyperkeratotic nail spicule.
Onychopapilloma. Longitudinal erythronychia originating at distal nail matrix/lunula, with splinter haemorrhage.
Onychopapilloma. Longitudinal excision with hyperplasia of nail bed and distal hyperkeratosis forming a spicule.
Onychopapilloma. Proximal matrical metaplasia of nail bed.
Onychopapilloma. Multinucleate nail bed keratinocytes.
Onychopapilloma. Distal nail bed digitation with hypergranulosis, reminiscent of verruca, and distal subungual parakeratosis/hyperkeratosis.
Onychopapilloma. The distal nail bed shows hypergranulosis, distal subungual parakeratosis/hyperkeratosis, and loculated haemorrhage.

Q: The distal nail bed in Onychopapilloma frequently demonstrates marked [...] and subungual hyperkeratosis, giving it a verruca-like appearance.
Onychopapilloma. Distal nail bed digitation with hypergranulosis, reminiscent of verruca, and distal subungual parakeratosis/hyperkeratosis.
Onychopapilloma. The distal nail bed shows hypergranulosis, distal subungual parakeratosis/hyperkeratosis, and loculated haemorrhage.
A: hypergranulosis
Back Extra: Onychopapilloma
- Clinical: Onychopapilloma typically presents with longitudinal erythronychia and distal subungual hyperkeratosis, often forming a spicule.
- Micro: Proximal nail bed may show matrical metaplasia, with multinucleate keratinocytes and hypergranulosis in the distal nail bed.
- Ancillary: No specific ancillary studies are typically required for the diagnosis of onychopapilloma.
Reference Gallery:
Onychopapilloma. Longitudinal erythronychia originating at distal nail matrix/lunula, with distal subungual hyperkeratotic nail spicule.
Onychopapilloma. Longitudinal erythronychia originating at distal nail matrix/lunula, with splinter haemorrhage.
Onychopapilloma. Longitudinal excision with hyperplasia of nail bed and distal hyperkeratosis forming a spicule.
Onychopapilloma. Proximal matrical metaplasia of nail bed.
Onychopapilloma. Multinucleate nail bed keratinocytes.
Onychopapilloma. Distal nail bed digitation with hypergranulosis, reminiscent of verruca, and distal subungual parakeratosis/hyperkeratosis.
Onychopapilloma. The distal nail bed shows hypergranulosis, distal subungual parakeratosis/hyperkeratosis, and loculated haemorrhage.

Q: Clinically, Subungual Keratoacanthoma presents as a painful nodule with nail dystrophy that often lacks spontaneous resolution and may radiographically show destruction of the underlying tuft of the [...].
Subungual keratoacanthoma. Fullness over nail matrix and bed with dystrophic nail plate and onycholysis (taken after an initial distal debridement procedure).
Subungual keratoacanthoma. Destruction of tuft of distal phalanx was confirmed radiographically, with small aggregates of bone adjacent to the tumour.
A: distal phalanx
Back Extra: Subungual Keratoacanthoma
- Clinical: Subungual keratoacanthoma presents as a painful nodule with subungual hyperkeratosis, often requiring surgical intervention due to lack of spontaneous resolution.
- Micro: Histologically, it shows a lobular proliferation of eosinophilic keratinocytes with vertical orientation, hyperkeratosis, and dyskeratotic keratinocytes.
- Ancillary: Amplification of genes encoding NF-κB1 and cortactin is observed in subungual keratoacanthoma but not in digital/subungual SCC, aiding in distinction.
Reference Gallery:
Subungual keratoacanthoma. Fullness over nail matrix and bed with dystrophic nail plate and onycholysis (taken after an initial distal debridement procedure).
Subungual keratoacanthoma. Features similar to those seen in incontinentia pigmenti, in a fragmented specimen.
Subungual keratoacanthoma. Features similar to those seen in incontinentia pigmenti, in a fragmented specimen.
Subungual keratoacanthoma. Destruction of tuft of distal phalanx was confirmed radiographically, with small aggregates of bone adjacent to the tumour.
Subungual tumour of incontinentia pigmenti. The findings are identical to those of subungual keratoacanthoma. Vertically oriented crateriform, lobular, and cystic proliferation of eosinophilic keratinocytes with associated hyperkeratosis, with overlying nail plate.
Subungual tumour of incontinentia pigmenti. The findings are identical to those of subungual keratoacanthoma. Numerous dyskeratotic keratinocytes in clusters throughout the epithelium and within hyperkeratosis, as well as calcification of keratinocytes and corneocytes.

Q: Histologically, Subungual Keratoacanthoma features a vertically oriented, crateriform, and lobular proliferation of [...], frequently accompanied by clusters of dyskeratotic cells.
Subungual tumour of incontinentia pigmenti. The findings are identical to those of subungual keratoacanthoma. Vertically oriented crateriform, lobular, and cystic proliferation of eosinophilic keratinocytes with associated hyperkeratosis, with overlying nail plate.
Subungual tumour of incontinentia pigmenti. The findings are identical to those of subungual keratoacanthoma. Numerous dyskeratotic keratinocytes in clusters throughout the epithelium and within hyperkeratosis, as well as calcification of keratinocytes and corneocytes.
A: eosinophilic keratinocytes
Back Extra: Subungual Keratoacanthoma
- Clinical: Subungual keratoacanthoma presents as a painful nodule with subungual hyperkeratosis, often requiring surgical intervention due to lack of spontaneous resolution.
- Micro: Histologically, it shows a lobular proliferation of eosinophilic keratinocytes with vertical orientation, hyperkeratosis, and dyskeratotic keratinocytes.
- Ancillary: Amplification of genes encoding NF-κB1 and cortactin is observed in subungual keratoacanthoma but not in digital/subungual SCC, aiding in distinction.
Reference Gallery:
Subungual keratoacanthoma. Fullness over nail matrix and bed with dystrophic nail plate and onycholysis (taken after an initial distal debridement procedure).
Subungual keratoacanthoma. Features similar to those seen in incontinentia pigmenti, in a fragmented specimen.
Subungual keratoacanthoma. Features similar to those seen in incontinentia pigmenti, in a fragmented specimen.
Subungual keratoacanthoma. Destruction of tuft of distal phalanx was confirmed radiographically, with small aggregates of bone adjacent to the tumour.
Subungual tumour of incontinentia pigmenti. The findings are identical to those of subungual keratoacanthoma. Vertically oriented crateriform, lobular, and cystic proliferation of eosinophilic keratinocytes with associated hyperkeratosis, with overlying nail plate.
Subungual tumour of incontinentia pigmenti. The findings are identical to those of subungual keratoacanthoma. Numerous dyskeratotic keratinocytes in clusters throughout the epithelium and within hyperkeratosis, as well as calcification of keratinocytes and corneocytes.

Q: Histologically, sebaceoma consists of well-circumscribed cellular lobules composed predominantly of small, monomorphic immature [...] cells, with a lesser population of mature sebocytes.
Sebaceoma. Low-power view showing a nodular proliferation of sebaceous and basaloid cells.
Sebaceoma. There is a predominance of basaloid cells; minimal cytological atypia may be seen.
A: basaloid
Back Extra: Sebaceoma
- Clinical: Sebaceomas are solitary, yellow-tan papules/nodules. They may rarely arise in a pre-existing sebaceous naevus and are more common in females, with a mean age of diagnosis at 70 years.
- Micro: Sebaceoma consists of well-circumscribed cellular lobules composed mostly of small, monomorphic immature basaloid cells with fewer mature sebocytes. Duct-like structures and cystic areas may be seen.
- Ancillary: Next-generation sequencing studies of sebaceomas have found frequent mutations in RAS family genes (HRAS and KRAS), TP53, CDKN2A, EGFR, and CTNNB1. EMA and adipophilin are immunohistochemical markers associated with the membranes of the cytoplasmic vacuoles.
Reference Gallery:
Sebaceoma. Low-power view showing a nodular proliferation of sebaceous and basaloid cells.
Sebaceoma. There is a predominance of basaloid cells; minimal cytological atypia may be seen.

Q: The adnexal tumor shown in the images, characterized by a nodular proliferation with a predominance of immature basaloid cells and a minor population of mature sebocytes, is a [...].
Sebaceoma. Low-power view showing a nodular proliferation of sebaceous and basaloid cells.
Sebaceoma. There is a predominance of basaloid cells; minimal cytological atypia may be seen.
A: sebaceoma
Back Extra: Sebaceoma
- Clinical: Sebaceomas are solitary, yellow-tan papules/nodules. They may rarely arise in a pre-existing sebaceous naevus and are more common in females, with a mean age of diagnosis at 70 years.
- Micro: Sebaceoma consists of well-circumscribed cellular lobules composed mostly of small, monomorphic immature basaloid cells with fewer mature sebocytes. Duct-like structures and cystic areas may be seen.
- Ancillary: Next-generation sequencing studies of sebaceomas have found frequent mutations in RAS family genes (HRAS and KRAS), TP53, CDKN2A, EGFR, and CTNNB1. EMA and adipophilin are immunohistochemical markers associated with the membranes of the cytoplasmic vacuoles.
Reference Gallery:
Sebaceoma. Low-power view showing a nodular proliferation of sebaceous and basaloid cells.
Sebaceoma. There is a predominance of basaloid cells; minimal cytological atypia may be seen.

Q: Microscopically, Sebaceous Adenoma is characterized by well-circumscribed lobular aggregates composed predominantly of mature sebocytes bordered by a peripheral rim of immature [...] cells.
Sebaceous adenoma. A well-circumscribed lobulated proliferation of sebocytes with admixed basaloid cells; sebocytes are predominant; minimal cytological atypia is present.
A: basaloid
Back Extra: Sebaceous Adenoma
- Clinical: Sebaceous adenoma is a well-circumscribed yellow-tan nodule, commonly found in sun-damaged skin of the head and neck area in individuals > 40 years old.
- Micro: Characterized by well-circumscribed lobular aggregates of mature sebocytes with a rim of immature basaloid cells, often connected to the overlying epidermis.
- Ancillary: Immunohistochemistry for MMR gene products (MLH1, MSH2, MSH6, PMS2) can help identify Muir–Torre syndrome, with loss of nuclear staining indicating deficient MMR.
Reference Gallery:
Sebaceous adenoma. A well-circumscribed lobulated proliferation of sebocytes with admixed basaloid cells; sebocytes are predominant; minimal cytological atypia is present.
Sebaceous adenoma. Low-power view of a cystic lesion containing predominantly clear cells (sebocytes). The patient had Muir–Torre syndrome.

Q: Patients diagnosed with Sebaceous Adenoma may have underlying [...], which can be screened for via immunohistochemical loss of nuclear mismatch repair (MMR) proteins.
Sebaceous adenoma. Low-power view of a cystic lesion containing predominantly clear cells (sebocytes). The patient had Muir–Torre syndrome.
A: Muir-Torre syndrome
Back Extra: Sebaceous Adenoma
- Clinical: Sebaceous adenoma is a well-circumscribed yellow-tan nodule, commonly found in sun-damaged skin of the head and neck area in individuals > 40 years old.
- Micro: Characterized by well-circumscribed lobular aggregates of mature sebocytes with a rim of immature basaloid cells, often connected to the overlying epidermis.
- Ancillary: Immunohistochemistry for MMR gene products (MLH1, MSH2, MSH6, PMS2) can help identify Muir–Torre syndrome, with loss of nuclear staining indicating deficient MMR.
Reference Gallery:
Sebaceous adenoma. A well-circumscribed lobulated proliferation of sebocytes with admixed basaloid cells; sebocytes are predominant; minimal cytological atypia is present.
Sebaceous adenoma. Low-power view of a cystic lesion containing predominantly clear cells (sebocytes). The patient had Muir–Torre syndrome.

Q: A characteristic histologic feature of NUT Carcinoma is the presence of undifferentiated tumor cells in solid aggregates or small ducts that exhibit foci of [...].
NUT carcinoma. In this BRD3::NUTM1-rearranged NUT adnexal carcinoma (HPS), the tumour cells are organized in strands, tubules, or solid aggregates with foci of abrupt keratinization.
NUT carcinoma. This BRD3::NUTM1-rearranged NUT adnexal carcinoma (HPS) shows the characteristic features of the presence of small round ducts and foci of abrupt keratinization.
A: abrupt keratinization
Back Extra: NUT Carcinoma
- Clinical: NUT carcinoma of the skin presents as a cutaneous papule or nodule, which may have been present for years, with potential regional metastatic spread at diagnosis.
- Micro: Tumour cells in NUT carcinoma are organized in strands, tubules, or solid aggregates, with characteristic features of small round ducts and foci of abrupt keratinization.
- Ancillary: NUT carcinoma shows positivity for EMA, CEA, CK5/6, CK7, p40, and SOX10 in immunohistochemistry, and molecular studies reveal BRD3::NUTM1, NSD3::NUTM1, or BRD3::NUTM2B gene fusions.
Reference Gallery:
NUT carcinoma. In this BRD3::NUTM1-rearranged NUT adnexal carcinoma (HPS), the tumour cells are organized in strands, tubules, or solid aggregates with foci of abrupt keratinization.
NUT carcinoma. This BRD3::NUTM1-rearranged NUT adnexal carcinoma (HPS) shows the characteristic features of the presence of small round ducts and foci of abrupt keratinization.
NUT carcinoma. This BRD3::NUTM1-rearranged NUT adnexal carcinoma consists of tumour cells with round nuclei and a prominent single nucleolus (HPS).
NUT carcinoma. This BRD3::NUTM1-rearranged NUT adnexal carcinoma consists of tumour cells with round nuclei and a prominent single nucleolus (HPS).

Q: At high magnification, the undifferentiated tumor cells of NUT Carcinoma classically possess round nuclei with a prominent single [...].
NUT carcinoma. This BRD3::NUTM1-rearranged NUT adnexal carcinoma consists of tumour cells with round nuclei and a prominent single nucleolus (HPS).
NUT carcinoma. This BRD3::NUTM1-rearranged NUT adnexal carcinoma consists of tumour cells with round nuclei and a prominent single nucleolus (HPS).
A: nucleolus
Back Extra: NUT Carcinoma
- Clinical: NUT carcinoma of the skin presents as a cutaneous papule or nodule, which may have been present for years, with potential regional metastatic spread at diagnosis.
- Micro: Tumour cells in NUT carcinoma are organized in strands, tubules, or solid aggregates, with characteristic features of small round ducts and foci of abrupt keratinization.
- Ancillary: NUT carcinoma shows positivity for EMA, CEA, CK5/6, CK7, p40, and SOX10 in immunohistochemistry, and molecular studies reveal BRD3::NUTM1, NSD3::NUTM1, or BRD3::NUTM2B gene fusions.
Reference Gallery:
NUT carcinoma. In this BRD3::NUTM1-rearranged NUT adnexal carcinoma (HPS), the tumour cells are organized in strands, tubules, or solid aggregates with foci of abrupt keratinization.
NUT carcinoma. This BRD3::NUTM1-rearranged NUT adnexal carcinoma (HPS) shows the characteristic features of the presence of small round ducts and foci of abrupt keratinization.
NUT carcinoma. This BRD3::NUTM1-rearranged NUT adnexal carcinoma consists of tumour cells with round nuclei and a prominent single nucleolus (HPS).
NUT carcinoma. This BRD3::NUTM1-rearranged NUT adnexal carcinoma consists of tumour cells with round nuclei and a prominent single nucleolus (HPS).

Q: Within the category of Other Benign Keratoses, [...] is characterized microscopically by epidermal acanthosis, a papillomatous growth pattern, and hyperkeratosis with prominent acantholysis lacking dyskeratosis.
Acantholytic acanthoma. Well-circumscribed keratosis characterized by epidermal thickening and acantholysis.
Acantholytic acanthoma. Higher magnification reveals prominent acantholysis with lack of dyskeratosis, reminiscent of benign chronic pemphigus (Hailey–Hailey disease).
A: acantholytic acanthoma
Back Extra: Other Benign Keratoses
- Clinical: Acantholytic acanthomas are solitary papules or nodules on the trunk of adults, with a male predominance.
- Micro: Acantholytic acanthoma shows epidermal acanthosis, a papillomatous growth pattern, and hyperkeratosis with prominent acantholysis.
- Ancillary: Immunohistochemistry for melan-A or HMB45 highlights dendritic melanocytes in melanoacanthoma.
Reference Gallery:
Acantholytic acanthoma. Well-circumscribed keratosis characterized by epidermal thickening and acantholysis.
Acantholytic acanthoma. Higher magnification reveals prominent acantholysis with lack of dyskeratosis, reminiscent of benign chronic pemphigus (Hailey–Hailey disease).
Melanoacanthoma. The prominent intralesional melanin pigment may lead to an erroneous diagnosis of a melanocytic lesion.
Melanoacanthoma. Immunohistochemistry for melan-A highlights colonization by dendritic melanocytes.

Q: Among Other Benign Keratoses, [...] is characterized by prominent intralesional melanin pigment and colonization by dendritic melanocytes, which can be highlighted by immunohistochemistry for melan-A or HMB45.
Melanoacanthoma. The prominent intralesional melanin pigment may lead to an erroneous diagnosis of a melanocytic lesion.
Melanoacanthoma. Immunohistochemistry for melan-A highlights colonization by dendritic melanocytes.
A: melanoacanthoma
Back Extra: Other Benign Keratoses
- Clinical: Acantholytic acanthomas are solitary papules or nodules on the trunk of adults, with a male predominance.
- Micro: Acantholytic acanthoma shows epidermal acanthosis, a papillomatous growth pattern, and hyperkeratosis with prominent acantholysis.
- Ancillary: Immunohistochemistry for melan-A or HMB45 highlights dendritic melanocytes in melanoacanthoma.
Reference Gallery:
Acantholytic acanthoma. Well-circumscribed keratosis characterized by epidermal thickening and acantholysis.
Acantholytic acanthoma. Higher magnification reveals prominent acantholysis with lack of dyskeratosis, reminiscent of benign chronic pemphigus (Hailey–Hailey disease).
Melanoacanthoma. The prominent intralesional melanin pigment may lead to an erroneous diagnosis of a melanocytic lesion.
Melanoacanthoma. Immunohistochemistry for melan-A highlights colonization by dendritic melanocytes.

Q: The hallmark histologic pattern of Clear Cell Acanthoma consists of cells with clear or pale cytoplasm arranged in a distinct [...] pattern of epidermal hyperplasia.
Clear cell acanthomas are characterized by psoriasiform epidermal hyperplasia with clear or pale cell change.
A: psoriasiform
Back Extra: Clear Cell Acanthoma
- Clinical: Patients present with sharply delineated, solitary, erythematous or brown papules and nodules, often showing a polypoid growth.
- Micro: Clear cell acanthomas are well circumscribed, with psoriasiform epidermal hyperplasia and elongated, fused rete ridges.
- Ancillary: Not relevant for diagnosis; clinical and histopathological features are sufficient.
Reference Gallery:
Clear cell acanthomas are characterized by psoriasiform epidermal hyperplasia with clear or pale cell change.
There is a sharp demarcation with the adjacent normal epidermis.
The tumour cells contain abundant clear cytoplasm. Also note the intralesional neutrophils and the dilated papillary vessels.

Q: Microscopically, Clear Cell Acanthoma features epidermal hyperplasia composed of pale tumor cells that exhibit a characteristic [...] from the adjacent normal epidermis.
There is a sharp demarcation with the adjacent normal epidermis.
A: sharp demarcation
Back Extra: Clear Cell Acanthoma
- Clinical: Patients present with sharply delineated, solitary, erythematous or brown papules and nodules, often showing a polypoid growth.
- Micro: Clear cell acanthomas are well circumscribed, with psoriasiform epidermal hyperplasia and elongated, fused rete ridges.
- Ancillary: Not relevant for diagnosis; clinical and histopathological features are sufficient.
Reference Gallery:
Clear cell acanthomas are characterized by psoriasiform epidermal hyperplasia with clear or pale cell change.
There is a sharp demarcation with the adjacent normal epidermis.
The tumour cells contain abundant clear cytoplasm. Also note the intralesional neutrophils and the dilated papillary vessels.

Q: In Clear Cell Acanthoma, the tumor typically contains intralesional neutrophils and characteristically exhibits [...] in the superficial dermis.
The tumour cells contain abundant clear cytoplasm. Also note the intralesional neutrophils and the dilated papillary vessels.
A: dilated papillary vessels
Back Extra: Clear Cell Acanthoma
- Clinical: Patients present with sharply delineated, solitary, erythematous or brown papules and nodules, often showing a polypoid growth.
- Micro: Clear cell acanthomas are well circumscribed, with psoriasiform epidermal hyperplasia and elongated, fused rete ridges.
- Ancillary: Not relevant for diagnosis; clinical and histopathological features are sufficient.
Reference Gallery:
Clear cell acanthomas are characterized by psoriasiform epidermal hyperplasia with clear or pale cell change.
There is a sharp demarcation with the adjacent normal epidermis.
The tumour cells contain abundant clear cytoplasm. Also note the intralesional neutrophils and the dilated papillary vessels.

Q: Histologically, Large Cell Acanthoma is characterized by a sharply demarcated epidermal proliferation of [...] that are typically twice the size of adjacent normal cells, with smooth nuclear contours and absent mitotic figures.
Large cell acanthoma. Large cell acanthomas show enlarged keratinocytes twice the size of adjacent normal keratinocytes. The nuclear contours are smooth, and mitotic figures are absent. Also note the overlying basket-weave orthokeratosis.
Large cell acanthoma. The hallmark feature is the presence of large keratinocytes with smooth nuclear contours and no signs of keratinocyte dysplasia.
A: enlarged keratinocytes
Back Extra: Large Cell Acanthoma
- Clinical: Large cell acanthomas appear as well-circumscribed tan to brown macules, typically less than 10 mm, found on chronically sun-exposed skin, especially in fair-skinned, middle-aged to elderly adults.
- Micro: Characterized by sharply delineated, enlarged keratinocytes with smooth nuclear contours, overlying basket-weave hyperkeratosis, and absence of mitotic figures.
- Ancillary: No relevant ancillary studies are needed for diagnosis.
Reference Gallery:
Large cell acanthoma. Large cell acanthomas show enlarged keratinocytes twice the size of adjacent normal keratinocytes. The nuclear contours are smooth, and mitotic figures are absent. Also note the overlying basket-weave orthokeratosis.
Large cell acanthoma. This epidermal tumour is sharply demarcated and shows acanthosis and overlying orthohyperkeratosis.
Large cell acanthoma. The hallmark feature is the presence of large keratinocytes with smooth nuclear contours and no signs of keratinocyte dysplasia.

Q: In Large Cell Acanthoma, the sharply delineated proliferation of large, non-dysplastic keratinocytes is characteristically topped by an overlying [...] orthohyperkeratosis.
Large cell acanthoma. Large cell acanthomas show enlarged keratinocytes twice the size of adjacent normal keratinocytes. The nuclear contours are smooth, and mitotic figures are absent. Also note the overlying basket-weave orthokeratosis.
Large cell acanthoma. This epidermal tumour is sharply demarcated and shows acanthosis and overlying orthohyperkeratosis.
A: basket-weave
Back Extra: Large Cell Acanthoma
- Clinical: Large cell acanthomas appear as well-circumscribed tan to brown macules, typically less than 10 mm, found on chronically sun-exposed skin, especially in fair-skinned, middle-aged to elderly adults.
- Micro: Characterized by sharply delineated, enlarged keratinocytes with smooth nuclear contours, overlying basket-weave hyperkeratosis, and absence of mitotic figures.
- Ancillary: No relevant ancillary studies are needed for diagnosis.
Reference Gallery:
Large cell acanthoma. Large cell acanthomas show enlarged keratinocytes twice the size of adjacent normal keratinocytes. The nuclear contours are smooth, and mitotic figures are absent. Also note the overlying basket-weave orthokeratosis.
Large cell acanthoma. This epidermal tumour is sharply demarcated and shows acanthosis and overlying orthohyperkeratosis.
Large cell acanthoma. The hallmark feature is the presence of large keratinocytes with smooth nuclear contours and no signs of keratinocyte dysplasia.

Q: In Lichen Planus-Like Keratosis, a key histologic feature is the presence of a [...] chronic inflammatory infiltrate in the superficial dermis, often accompanied by epidermal hyperplasia.
Lichen planus–like keratosis. There is epidermal hyperplasia and a band-like chronic inflammatory infiltrate in the superficial dermis.
A: band-like
Back Extra: Lichen Planus-Like Keratosis
- Clinical: Lichen planus-like keratoses are solitary erythematous, violaceous, or brown macules and plaques, commonly affecting middle-aged to elderly adults, with a female predilection.
- Micro: Characterized by well-circumscribed intraepidermal keratinocytic proliferations with epidermal hyperplasia, hyperkeratosis, and a band-like inflammatory infiltrate in the superficial dermis.
- Ancillary: Mutations in FGFR3, PIK3CA, HRAS, and KRAS may be identified, but diagnostic molecular pathology is not typically required.
Reference Gallery:
Lichen planus–like keratosis. There is epidermal hyperplasia and a band-like chronic inflammatory infiltrate in the superficial dermis.
Lichen planus–like keratosis. Note the vacuolar interface change, with numerous apoptotic keratinocytes and a superficial dermal chronic inflammatory infiltrate showing pigment incontinence.

Q: Microscopically, Lichen Planus-Like Keratosis frequently demonstrates a [...] change at the dermoepidermal junction, accompanied by numerous apoptotic keratinocytes and pigment incontinence.
Lichen planus–like keratosis. Note the vacuolar interface change, with numerous apoptotic keratinocytes and a superficial dermal chronic inflammatory infiltrate showing pigment incontinence.
A: vacuolar interface
Back Extra: Lichen Planus-Like Keratosis
- Clinical: Lichen planus-like keratoses are solitary erythematous, violaceous, or brown macules and plaques, commonly affecting middle-aged to elderly adults, with a female predilection.
- Micro: Characterized by well-circumscribed intraepidermal keratinocytic proliferations with epidermal hyperplasia, hyperkeratosis, and a band-like inflammatory infiltrate in the superficial dermis.
- Ancillary: Mutations in FGFR3, PIK3CA, HRAS, and KRAS may be identified, but diagnostic molecular pathology is not typically required.
Reference Gallery:
Lichen planus–like keratosis. There is epidermal hyperplasia and a band-like chronic inflammatory infiltrate in the superficial dermis.
Lichen planus–like keratosis. Note the vacuolar interface change, with numerous apoptotic keratinocytes and a superficial dermal chronic inflammatory infiltrate showing pigment incontinence.

Q: Microscopically, Seborrhoeic Keratosis is a well-circumscribed, papillomatous proliferation of basaloid keratinocytes that classically features the formation of [...].
Seborrhoeic keratosis. Seborrhoeic keratoses are well-circumscribed with a papillomatous architecture and a flat base.
Acanthotic seborrhoeic keratosis. The acanthotic pattern is composed of broad columns of neoplastic keratinocytes with “horn cyst” formation.
A: horn cysts
Back Extra: Seborrhoeic Keratosis
- Clinical: Seborrhoeic keratoses may appear as tan to brown or black, flat-based warty papules and plaques with a stuck-on appearance.
- Micro: Seborrhoeic keratoses are intraepidermal proliferations of basaloid keratinocytes, characterized by a well-circumscribed, papillomatous architecture with horn cysts.
- Ancillary: Oncogenic mutations such as FGFR3, PIK3CA, KRAS, HRAS, EGFR, AKT1, TERT, and DPH3 are noted in seborrhoeic keratoses.
Reference Gallery:
Seborrhoeic keratosis. Seborrhoeic keratoses are well-circumscribed with a papillomatous architecture and a flat base.
Seborrhoeic keratosis. Seborrhoeic keratoses are composed of bland polygonal basaloid cells without cytological atypia.
Acanthotic seborrhoeic keratosis. The acanthotic pattern is composed of broad columns of neoplastic keratinocytes with “horn cyst” formation.
Keratotic seborrhoeic keratosis. The keratotic pattern shows marked papillomatosis and hyperkeratosis.
Adenoid seborrhoeic keratosis. The adenoid pattern is characterized by interconnecting elongated rete ridges with horn cyst formation.
Clonal seborrhoeic keratosis. The clonal pattern shows intraepidermal nests of neoplastic keratinocytes giving rise to the Borst–Jadassohn pattern.
Irritated seborrhoeic keratosis. Hallmark features of the irritated subtype are areas of squamatization with squamous eddy formation.
Pigmented seborrhoeic keratosis. The pigmented pattern shows extensive cytoplasmic melanin pigmentation of the neoplastic keratinocytes.

Q: The irritated variant of Seborrhoeic Keratosis is characterized by areas of squamatization with the hallmark formation of [...].
Irritated seborrhoeic keratosis. Hallmark features of the irritated subtype are areas of squamatization with squamous eddy formation.
A: squamous eddies
Back Extra: Seborrhoeic Keratosis
- Clinical: Seborrhoeic keratoses may appear as tan to brown or black, flat-based warty papules and plaques with a stuck-on appearance.
- Micro: Seborrhoeic keratoses are intraepidermal proliferations of basaloid keratinocytes, characterized by a well-circumscribed, papillomatous architecture with horn cysts.
- Ancillary: Oncogenic mutations such as FGFR3, PIK3CA, KRAS, HRAS, EGFR, AKT1, TERT, and DPH3 are noted in seborrhoeic keratoses.
Reference Gallery:
Seborrhoeic keratosis. Seborrhoeic keratoses are well-circumscribed with a papillomatous architecture and a flat base.
Seborrhoeic keratosis. Seborrhoeic keratoses are composed of bland polygonal basaloid cells without cytological atypia.
Acanthotic seborrhoeic keratosis. The acanthotic pattern is composed of broad columns of neoplastic keratinocytes with “horn cyst” formation.
Keratotic seborrhoeic keratosis. The keratotic pattern shows marked papillomatosis and hyperkeratosis.
Adenoid seborrhoeic keratosis. The adenoid pattern is characterized by interconnecting elongated rete ridges with horn cyst formation.
Clonal seborrhoeic keratosis. The clonal pattern shows intraepidermal nests of neoplastic keratinocytes giving rise to the Borst–Jadassohn pattern.
Irritated seborrhoeic keratosis. Hallmark features of the irritated subtype are areas of squamatization with squamous eddy formation.
Pigmented seborrhoeic keratosis. The pigmented pattern shows extensive cytoplasmic melanin pigmentation of the neoplastic keratinocytes.

Q: The clonal pattern of Seborrhoeic Keratosis demonstrates distinct intraepidermal nests of neoplastic keratinocytes, known as the [...] pattern.
Clonal seborrhoeic keratosis. The clonal pattern shows intraepidermal nests of neoplastic keratinocytes giving rise to the Borst–Jadassohn pattern.
A: Borst-Jadassohn
Back Extra: Seborrhoeic Keratosis
- Clinical: Seborrhoeic keratoses may appear as tan to brown or black, flat-based warty papules and plaques with a stuck-on appearance.
- Micro: Seborrhoeic keratoses are intraepidermal proliferations of basaloid keratinocytes, characterized by a well-circumscribed, papillomatous architecture with horn cysts.
- Ancillary: Oncogenic mutations such as FGFR3, PIK3CA, KRAS, HRAS, EGFR, AKT1, TERT, and DPH3 are noted in seborrhoeic keratoses.
Reference Gallery:
Seborrhoeic keratosis. Seborrhoeic keratoses are well-circumscribed with a papillomatous architecture and a flat base.
Seborrhoeic keratosis. Seborrhoeic keratoses are composed of bland polygonal basaloid cells without cytological atypia.
Acanthotic seborrhoeic keratosis. The acanthotic pattern is composed of broad columns of neoplastic keratinocytes with “horn cyst” formation.
Keratotic seborrhoeic keratosis. The keratotic pattern shows marked papillomatosis and hyperkeratosis.
Adenoid seborrhoeic keratosis. The adenoid pattern is characterized by interconnecting elongated rete ridges with horn cyst formation.
Clonal seborrhoeic keratosis. The clonal pattern shows intraepidermal nests of neoplastic keratinocytes giving rise to the Borst–Jadassohn pattern.
Irritated seborrhoeic keratosis. Hallmark features of the irritated subtype are areas of squamatization with squamous eddy formation.
Pigmented seborrhoeic keratosis. The pigmented pattern shows extensive cytoplasmic melanin pigmentation of the neoplastic keratinocytes.

Q: On low-power microscopy, Warty Dyskeratoma typically presents as a well-circumscribed, [...] epidermal invagination containing a central parakeratotic plug.
Warty dyskeratoma. Note the lesional circumscription and slightly endophytic architecture on low-power magnification.
Warty dyskeratoma. Suprabasilar acantholysis and a central parakeratotic plug are present.
A: cup-shaped
Back Extra: Warty Dyskeratoma
- Clinical: Warty dyskeratomas appear as solitary tan to light-brown papules or small nodules, may appear umbilicated, and are typically found on the head and neck area in elderly individuals.
- Micro: Warty dyskeratoma is a well-circumscribed, cup-shaped epidermal invagination with prominent acantholysis, suprabasal clefting, dyskeratosis, and an overlying parakeratotic plug.
- Ancillary: Ancillary studies are not relevant for the diagnosis of warty dyskeratoma.
Reference Gallery:
Warty dyskeratoma. Note the lesional circumscription and slightly endophytic architecture on low-power magnification.
Warty dyskeratoma. Suprabasilar acantholysis and a central parakeratotic plug are present.
Warty dyskeratoma. Note the suprabasilar acantholysis and the dyskeratotic cells on higher magnification.

Q: Microscopically, the characteristic findings within the invagination of Warty Dyskeratoma include dyskeratotic cells and prominent suprabasilar [...].
Warty dyskeratoma. Suprabasilar acantholysis and a central parakeratotic plug are present.
Warty dyskeratoma. Note the suprabasilar acantholysis and the dyskeratotic cells on higher magnification.
A: acantholysis
Back Extra: Warty Dyskeratoma
- Clinical: Warty dyskeratomas appear as solitary tan to light-brown papules or small nodules, may appear umbilicated, and are typically found on the head and neck area in elderly individuals.
- Micro: Warty dyskeratoma is a well-circumscribed, cup-shaped epidermal invagination with prominent acantholysis, suprabasal clefting, dyskeratosis, and an overlying parakeratotic plug.
- Ancillary: Ancillary studies are not relevant for the diagnosis of warty dyskeratoma.
Reference Gallery:
Warty dyskeratoma. Note the lesional circumscription and slightly endophytic architecture on low-power magnification.
Warty dyskeratoma. Suprabasilar acantholysis and a central parakeratotic plug are present.
Warty dyskeratoma. Note the suprabasilar acantholysis and the dyskeratotic cells on higher magnification.

Q: In Basal Cell Carcinoma with Adnexal Differentiation, the matrical variant is histologically characterized by infiltrative basaloid islands containing [...].
Basal cell carcinoma with matrical differentiation. Infiltrative basaloid tumour containing islands of shadow cells indicative of hair matrix differentiation.
A: shadow cells
Back Extra: Basal Cell Carcinoma with Adnexal Differentiation
- Clinical: Basal cell carcinoma with adnexal differentiation often presents in periocular skin, similar to other BCCs.
- Micro: This variant of BCC can show various patterns, including matrical, infundibulocystic, and sebaceous differentiation, with characteristic features like shadow cells and mature sebocytes.
- Ancillary: Genetic alterations in SUFU, SMO, GLI1, GLI2, and PTCH1 are common in these tumours, supporting their association with the hedgehog pathway.
Reference Gallery:
Basal cell carcinoma with matrical differentiation. Infiltrative basaloid tumour containing islands of shadow cells indicative of hair matrix differentiation.
Infundibulocystic basal cell carcinoma. Anastomosing cords of basaloid tumour cells punctuated by small keratin-filled cysts.
Basal cell carcinoma with sebaceous differentiation. Basaloid tumour containing multivacuolated mature sebocytes, consistent with sebaceous differentiation.

Q: The infundibulocystic pattern of Basal Cell Carcinoma with Adnexal Differentiation features anastomosing cords of basaloid cells punctuated by small [...].
Infundibulocystic basal cell carcinoma. Anastomosing cords of basaloid tumour cells punctuated by small keratin-filled cysts.
A: keratin-filled cysts
Back Extra: Basal Cell Carcinoma with Adnexal Differentiation
- Clinical: Basal cell carcinoma with adnexal differentiation often presents in periocular skin, similar to other BCCs.
- Micro: This variant of BCC can show various patterns, including matrical, infundibulocystic, and sebaceous differentiation, with characteristic features like shadow cells and mature sebocytes.
- Ancillary: Genetic alterations in SUFU, SMO, GLI1, GLI2, and PTCH1 are common in these tumours, supporting their association with the hedgehog pathway.
Reference Gallery:
Basal cell carcinoma with matrical differentiation. Infiltrative basaloid tumour containing islands of shadow cells indicative of hair matrix differentiation.
Infundibulocystic basal cell carcinoma. Anastomosing cords of basaloid tumour cells punctuated by small keratin-filled cysts.
Basal cell carcinoma with sebaceous differentiation. Basaloid tumour containing multivacuolated mature sebocytes, consistent with sebaceous differentiation.

Q: When Basal Cell Carcinoma with Adnexal Differentiation exhibits a sebaceous pattern, the basaloid tumor uniquely contains multivacuolated [...].
Basal cell carcinoma with sebaceous differentiation. Basaloid tumour containing multivacuolated mature sebocytes, consistent with sebaceous differentiation.
A: mature sebocytes
Back Extra: Basal Cell Carcinoma with Adnexal Differentiation
- Clinical: Basal cell carcinoma with adnexal differentiation often presents in periocular skin, similar to other BCCs.
- Micro: This variant of BCC can show various patterns, including matrical, infundibulocystic, and sebaceous differentiation, with characteristic features like shadow cells and mature sebocytes.
- Ancillary: Genetic alterations in SUFU, SMO, GLI1, GLI2, and PTCH1 are common in these tumours, supporting their association with the hedgehog pathway.
Reference Gallery:
Basal cell carcinoma with matrical differentiation. Infiltrative basaloid tumour containing islands of shadow cells indicative of hair matrix differentiation.
Infundibulocystic basal cell carcinoma. Anastomosing cords of basaloid tumour cells punctuated by small keratin-filled cysts.
Basal cell carcinoma with sebaceous differentiation. Basaloid tumour containing multivacuolated mature sebocytes, consistent with sebaceous differentiation.

Q: Clinically, Fibroepithelial Basal Cell Carcinoma typically presents on the trunk as an exophytic, flesh-colored nodule that frequently mimics a benign [...].
Fibroepithelial basal cell carcinoma. Clinical image of fibroepithelial basal cell carcinoma, showing a flesh-coloured nodule.
A: fibroepithelial polyp
Back Extra: Fibroepithelial Basal Cell Carcinoma
- Clinical: Fibroepithelial basal cell carcinoma appears as an exophytic, flesh-coloured nodule, often resembling a fibroepithelial polyp, and may be pigmented. It is most common on the trunk, especially the lateral hip and back.
- Micro: Histopathologically, it shows multiple strands of basaloid epithelium with peripheral palisades emanating from the epidermis, surrounded by abundant fibroblastic, eosinophilic stroma.
- Ancillary: Not relevant for diagnosis.
Reference Gallery:
Fibroepithelial basal cell carcinoma. Clinical image of fibroepithelial basal cell carcinoma, showing a flesh-coloured nodule.
Fibroepithelial basal cell carcinoma. Dermoscopic appearance of a fibroepithelial basal cell carcinoma.
Fibroepithelial basal cell carcinoma. An example showing growth of reticulated strands of basaloid epithelium connected to epidermis.
Fibroepithelial basal cell carcinoma. The tumour demonstrates compressed strands of basaloid epithelium with focal peripheral palisading and abundant intervening fibrous stroma.
Fibroepithelial basal cell carcinoma. Basaloid strands emanate from epidermis and are surrounded by fibroblastic stroma.

Q: Microscopically, Fibroepithelial Basal Cell Carcinoma is characterized by multiple interconnected strands of [...] with focal peripheral palisading, which emanate from the epidermis into an abundant fibroblastic stroma.
Fibroepithelial basal cell carcinoma. An example showing growth of reticulated strands of basaloid epithelium connected to epidermis.
Fibroepithelial basal cell carcinoma. The tumour demonstrates compressed strands of basaloid epithelium with focal peripheral palisading and abundant intervening fibrous stroma.
Fibroepithelial basal cell carcinoma. Basaloid strands emanate from epidermis and are surrounded by fibroblastic stroma.
A: basaloid epithelium
Back Extra: Fibroepithelial Basal Cell Carcinoma
- Clinical: Fibroepithelial basal cell carcinoma appears as an exophytic, flesh-coloured nodule, often resembling a fibroepithelial polyp, and may be pigmented. It is most common on the trunk, especially the lateral hip and back.
- Micro: Histopathologically, it shows multiple strands of basaloid epithelium with peripheral palisades emanating from the epidermis, surrounded by abundant fibroblastic, eosinophilic stroma.
- Ancillary: Not relevant for diagnosis.
Reference Gallery:
Fibroepithelial basal cell carcinoma. Clinical image of fibroepithelial basal cell carcinoma, showing a flesh-coloured nodule.
Fibroepithelial basal cell carcinoma. Dermoscopic appearance of a fibroepithelial basal cell carcinoma.
Fibroepithelial basal cell carcinoma. An example showing growth of reticulated strands of basaloid epithelium connected to epidermis.
Fibroepithelial basal cell carcinoma. The tumour demonstrates compressed strands of basaloid epithelium with focal peripheral palisading and abundant intervening fibrous stroma.
Fibroepithelial basal cell carcinoma. Basaloid strands emanate from epidermis and are surrounded by fibroblastic stroma.

Q: Clinically, Infiltrating Basal Cell Carcinoma often presents as a pink, scar-like plaque or papule, which on dermoscopy classically demonstrates thin, [...] vessels.
Infiltrating basal cell carcinoma. Clinical photograph of an infiltrating basal cell carcinoma, showing depressed pink scar-like papule.
Infiltrating basal cell carcinoma. Dermoscopic image of infiltrating basal cell carcinoma showing white papule with serpentine vessels.
A: serpentine
Back Extra: Infiltrating Basal Cell Carcinoma
- Clinical: Infiltrating basal cell carcinomas are typically pink papules or plaques, often ulcerated and may appear scar-like.
- Micro: Characterized by irregular, jagged nests of basaloid tumour cells infiltrating the dermal collagen, often with a sclerotic stroma.
- Ancillary: Not relevant for diagnosis, but dermoscopy can help in identifying thin serpentine vessels.
Reference Gallery:
Infiltrating basal cell carcinoma. Clinical photograph of an infiltrating basal cell carcinoma, showing depressed pink scar-like papule.
Infiltrating basal cell carcinoma. Dermoscopic image of infiltrating basal cell carcinoma showing white papule with serpentine vessels.
Infiltrating basal cell carcinoma. Low-power photomicrograph of infiltrating basal cell carcinoma showing irregular deep border with jagged tumour nests.
Infiltrating basal cell carcinoma. Narrow tumour islands compressed by collagen with fibromyxoid appearance.

Q: Histologically, Infiltrating Basal Cell Carcinoma is defined by irregular, [...] nests and narrow cords of basaloid tumor cells infiltrating a sclerotic dermal stroma.
Infiltrating basal cell carcinoma. Low-power photomicrograph of infiltrating basal cell carcinoma showing irregular deep border with jagged tumour nests.
Infiltrating basal cell carcinoma. Narrow tumour islands compressed by collagen with fibromyxoid appearance.
A: jagged
Back Extra: Infiltrating Basal Cell Carcinoma
- Clinical: Infiltrating basal cell carcinomas are typically pink papules or plaques, often ulcerated and may appear scar-like.
- Micro: Characterized by irregular, jagged nests of basaloid tumour cells infiltrating the dermal collagen, often with a sclerotic stroma.
- Ancillary: Not relevant for diagnosis, but dermoscopy can help in identifying thin serpentine vessels.
Reference Gallery:
Infiltrating basal cell carcinoma. Clinical photograph of an infiltrating basal cell carcinoma, showing depressed pink scar-like papule.
Infiltrating basal cell carcinoma. Dermoscopic image of infiltrating basal cell carcinoma showing white papule with serpentine vessels.
Infiltrating basal cell carcinoma. Low-power photomicrograph of infiltrating basal cell carcinoma showing irregular deep border with jagged tumour nests.
Infiltrating basal cell carcinoma. Narrow tumour islands compressed by collagen with fibromyxoid appearance.

Q: The histologic hallmark of Micronodular Basal Cell Carcinoma is the presence of widely separated [...] of basaloid cells within a fibrous stroma, often displaying an irregular, infiltrative deep edge.
Micronodular basal cell carcinoma. Micronodular basal cell carcinoma shows small nests separated by fibrous stroma.
Micronodular basal cell carcinoma. High-power detail of small, widely separated nests of micronodular basal cell carcinoma.
A: small nests
Back Extra: Micronodular Basal Cell Carcinoma
- Clinical: Micronodular basal cell carcinoma typically presents as a pink papule or nodule, often ulcerated, and is most commonly situated on the head and neck.
- Micro: Micronodular basal cell carcinoma is characterized by small nests of basaloid cells separated by fibrous stroma, with an irregular, tentacular, and infiltrative deep or peripheral edge.
- Ancillary: Prognostic data for micronodular basal cell carcinoma are limited, but it is associated with an increased risk of local recurrence.
Reference Gallery:
Micronodular basal cell carcinoma (clinical photo). Micronodular basal cell carcinoma usually presents as a pink papule or nodule. It is often ulcerated and cannot be distinguished from nodular basal cell carcinoma on naked-eye examination or dermoscopy.
Micronodular basal cell carcinoma. Micronodular basal cell carcinoma shows small nests separated by fibrous stroma.
Micronodular basal cell carcinoma. High-power detail of small, widely separated nests of micronodular basal cell carcinoma.

Q: Although clinically presenting as a typical pink, often ulcerated papule or nodule on the head and neck, Micronodular Basal Cell Carcinoma is prognostically associated with an increased risk of [...].
Micronodular basal cell carcinoma (clinical photo). Micronodular basal cell carcinoma usually presents as a pink papule or nodule. It is often ulcerated and cannot be distinguished from nodular basal cell carcinoma on naked-eye examination or dermoscopy.
A: local recurrence
Back Extra: Micronodular Basal Cell Carcinoma
- Clinical: Micronodular basal cell carcinoma typically presents as a pink papule or nodule, often ulcerated, and is most commonly situated on the head and neck.
- Micro: Micronodular basal cell carcinoma is characterized by small nests of basaloid cells separated by fibrous stroma, with an irregular, tentacular, and infiltrative deep or peripheral edge.
- Ancillary: Prognostic data for micronodular basal cell carcinoma are limited, but it is associated with an increased risk of local recurrence.
Reference Gallery:
Micronodular basal cell carcinoma (clinical photo). Micronodular basal cell carcinoma usually presents as a pink papule or nodule. It is often ulcerated and cannot be distinguished from nodular basal cell carcinoma on naked-eye examination or dermoscopy.
Micronodular basal cell carcinoma. Micronodular basal cell carcinoma shows small nests separated by fibrous stroma.
Micronodular basal cell carcinoma. High-power detail of small, widely separated nests of micronodular basal cell carcinoma.

Q: Clinically, Sclerosing/Morphoeic Basal Cell Carcinoma often presents as a poorly defined, scar-like plaque, and dermoscopy classically reveals [...].
Sclerosing/morphoeic basal cell carcinoma. Clinical photograph of sclerosing/morphoeic basal cell carcinoma showing depressed white plaque with telangiectasia.
Sclerosing/morphoeic basal cell carcinoma. Dermoscopy of morphoeic basal cell carcinoma shows thin, serpentine vessels.
A: thin serpentine vessels
Back Extra: Sclerosing/Morphoeic Basal Cell Carcinoma
- Clinical: Patients with Sclerosing/Morphoeic Basal Cell Carcinoma present with a poorly defined, scar-like plaque that rarely ulcerates or bleeds, and dermoscopy shows thin serpentine vessels.
- Micro: Narrow cords of tumour (1–5 cells thick) are compressed by induced sclerotic collagenous stroma, disrupting the normal dermal architecture. These tumours show an irregular/tentacular, deeply infiltrative border.
- Ancillary: Fibroblast activation protein is positive in stromal fibroblasts of Sclerosing/Morphoeic BCC, and laminin-γ2 shows a cytoplasmic staining pattern in this type of BCC.
Reference Gallery:
Sclerosing/morphoeic basal cell carcinoma. Sclerosing/morphoeic basal cell carcinoma showing jagged tumour islands surrounded by abundant fibrocellular stroma.
Sclerosing/morphoeic basal cell carcinoma. Sclerosing/morphoeic basal cell carcinoma showing cellular preponderance of fibrocollagenous stroma compressing tumour islands.
Sclerosing/morphoeic basal cell carcinoma. Clinical photograph of sclerosing/morphoeic basal cell carcinoma showing depressed white plaque with telangiectasia.
Sclerosing/morphoeic basal cell carcinoma. Dermoscopy of morphoeic basal cell carcinoma shows thin, serpentine vessels.

Q: Histologically, Sclerosing/Morphoeic Basal Cell Carcinoma features narrow cords of tumor cells with an irregular, deeply infiltrative border that are compressed by a dense, [...].
Sclerosing/morphoeic basal cell carcinoma. Sclerosing/morphoeic basal cell carcinoma showing jagged tumour islands surrounded by abundant fibrocellular stroma.
Sclerosing/morphoeic basal cell carcinoma. Sclerosing/morphoeic basal cell carcinoma showing cellular preponderance of fibrocollagenous stroma compressing tumour islands.
A: sclerotic collagenous stroma
Back Extra: Sclerosing/Morphoeic Basal Cell Carcinoma
- Clinical: Patients with Sclerosing/Morphoeic Basal Cell Carcinoma present with a poorly defined, scar-like plaque that rarely ulcerates or bleeds, and dermoscopy shows thin serpentine vessels.
- Micro: Narrow cords of tumour (1–5 cells thick) are compressed by induced sclerotic collagenous stroma, disrupting the normal dermal architecture. These tumours show an irregular/tentacular, deeply infiltrative border.
- Ancillary: Fibroblast activation protein is positive in stromal fibroblasts of Sclerosing/Morphoeic BCC, and laminin-γ2 shows a cytoplasmic staining pattern in this type of BCC.
Reference Gallery:
Sclerosing/morphoeic basal cell carcinoma. Sclerosing/morphoeic basal cell carcinoma showing jagged tumour islands surrounded by abundant fibrocellular stroma.
Sclerosing/morphoeic basal cell carcinoma. Sclerosing/morphoeic basal cell carcinoma showing cellular preponderance of fibrocollagenous stroma compressing tumour islands.
Sclerosing/morphoeic basal cell carcinoma. Clinical photograph of sclerosing/morphoeic basal cell carcinoma showing depressed white plaque with telangiectasia.
Sclerosing/morphoeic basal cell carcinoma. Dermoscopy of morphoeic basal cell carcinoma shows thin, serpentine vessels.

Q: Clinically, Nodular Basal Cell Carcinoma classically presents on the head and neck as a pink, pearly papule or nodule with prominent [...] vessels and occasional ulceration or pigmentation.
Nodular basal cell carcinoma. Nodular basal cell carcinoma with focal pigmentation, demonstrating pearly papulonodule with telangiectatic vessels centrally.
Nodular basal cell carcinoma. Dermoscopy of nodular basal cell carcinoma shows blue, brown, and white globules, as well as serpentine vessels.
A: telangiectatic
Back Extra: Nodular Basal Cell Carcinoma
- Clinical: Patients with nodular basal cell carcinoma (BCC) present with a pink papule or nodule with frequent ulceration and occasionally pigmentation, most commonly in the head and neck region.
- Micro: Microscopically, nodular BCC shows well-circumscribed nodules of basaloid cells with peripheral palisading and retraction spaces, and disorganized nuclear arrangement with apoptosis in the center of the nodules.
- Ancillary: Ancillary studies are not typically required for the diagnosis of nodular BCC, which relies primarily on clinical and histopathological features.
Reference Gallery:
Nodular basal cell carcinoma. Nodular basal cell carcinoma with focal pigmentation, demonstrating pearly papulonodule with telangiectatic vessels centrally.
Nodular basal cell carcinoma. Dermoscopy of nodular basal cell carcinoma shows blue, brown, and white globules, as well as serpentine vessels.
Nodular basal cell carcinoma. Nodular basal cell carcinoma with several patterns, including cystic change and focal keratinization.

Q: Microscopically, Nodular Basal Cell Carcinoma is characterized by well-circumscribed nodules of basaloid cells exhibiting characteristic [...] and artifactual retraction spaces from the surrounding stroma.
Nodular basal cell carcinoma. Nodular basal cell carcinoma with several patterns, including cystic change and focal keratinization.
A: peripheral palisading
Back Extra: Nodular Basal Cell Carcinoma
- Clinical: Patients with nodular basal cell carcinoma (BCC) present with a pink papule or nodule with frequent ulceration and occasionally pigmentation, most commonly in the head and neck region.
- Micro: Microscopically, nodular BCC shows well-circumscribed nodules of basaloid cells with peripheral palisading and retraction spaces, and disorganized nuclear arrangement with apoptosis in the center of the nodules.
- Ancillary: Ancillary studies are not typically required for the diagnosis of nodular BCC, which relies primarily on clinical and histopathological features.
Reference Gallery:
Nodular basal cell carcinoma. Nodular basal cell carcinoma with focal pigmentation, demonstrating pearly papulonodule with telangiectatic vessels centrally.
Nodular basal cell carcinoma. Dermoscopy of nodular basal cell carcinoma shows blue, brown, and white globules, as well as serpentine vessels.
Nodular basal cell carcinoma. Nodular basal cell carcinoma with several patterns, including cystic change and focal keratinization.

Q: Microscopically, [...] features typical nodules of basaloid cells with peripheral nuclear palisading that are intimately mixed with a hypercellular, malignant mesenchymal stroma.
Basal cell carcinoma with sarcomatoid differentiation. Low-power view showing islands of basaloid cells separated by cellular stroma, which at higher power shows evidence of malignancy (screenshot from whole slide imaging).
Basal cell carcinoma with sarcomatoid differentiation. Higher-power view showing sarcomatous stroma to the left and typical nodules of basaloid cells with peripheral nuclear palisading on the right (screenshot from whole slide imaging).
A: Basal Cell Carcinoma with Sarcomatoid Differentiation
Back Extra: Basal Cell Carcinoma with Sarcomatoid Differentiation
- Clinical: Patients present with a rapidly growing new lesion or rapid enlargement of a longer-standing lesion, typically on sun-exposed skin of elderly White men.
- Micro: Nodules of basal cell carcinoma are separated by a malignant mesenchymal stroma that can resemble various types of sarcoma, including pleomorphic undifferentiated sarcoma, osteosarcoma, and chondrosarcoma.
- Ancillary: Staging follows the eighth edition of the Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) TNM system.
Reference Gallery:
Basal cell carcinoma with sarcomatoid differentiation. Low-power view showing islands of basaloid cells separated by cellular stroma, which at higher power shows evidence of malignancy (screenshot from whole slide imaging).
Basal cell carcinoma with sarcomatoid differentiation. Higher-power view showing sarcomatous stroma to the left and typical nodules of basaloid cells with peripheral nuclear palisading on the right (screenshot from whole slide imaging).
Basal cell carcinoma with sarcomatoid differentiation. Nests of basal cell carcinoma are surrounded by a hypercellular, predominantly spindle cell sarcomatoid stromal component. A focal area shows osteosarcomatous differentiation.
Basal cell carcinoma with sarcomatoid differentiation. Higher magnification detailing nests of basal cell carcinoma surrounded by hypercellular sarcomatoid stroma, which includes atypical plump and spindle cells in a fibromyxoid background.

Q: In Basal Cell Carcinoma with Sarcomatoid Differentiation, the malignant mesenchymal stroma often contains atypical spindle cells and can show heterologous elements, such as focal [...] or chondrosarcomatous differentiation.
Basal cell carcinoma with sarcomatoid differentiation. Nests of basal cell carcinoma are surrounded by a hypercellular, predominantly spindle cell sarcomatoid stromal component. A focal area shows osteosarcomatous differentiation.
Basal cell carcinoma with sarcomatoid differentiation. Higher magnification detailing nests of basal cell carcinoma surrounded by hypercellular sarcomatoid stroma, which includes atypical plump and spindle cells in a fibromyxoid background.
A: osteosarcomatous
Back Extra: Basal Cell Carcinoma with Sarcomatoid Differentiation
- Clinical: Patients present with a rapidly growing new lesion or rapid enlargement of a longer-standing lesion, typically on sun-exposed skin of elderly White men.
- Micro: Nodules of basal cell carcinoma are separated by a malignant mesenchymal stroma that can resemble various types of sarcoma, including pleomorphic undifferentiated sarcoma, osteosarcoma, and chondrosarcoma.
- Ancillary: Staging follows the eighth edition of the Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) TNM system.
Reference Gallery:
Basal cell carcinoma with sarcomatoid differentiation. Low-power view showing islands of basaloid cells separated by cellular stroma, which at higher power shows evidence of malignancy (screenshot from whole slide imaging).
Basal cell carcinoma with sarcomatoid differentiation. Higher-power view showing sarcomatous stroma to the left and typical nodules of basaloid cells with peripheral nuclear palisading on the right (screenshot from whole slide imaging).
Basal cell carcinoma with sarcomatoid differentiation. Nests of basal cell carcinoma are surrounded by a hypercellular, predominantly spindle cell sarcomatoid stromal component. A focal area shows osteosarcomatous differentiation.
Basal cell carcinoma with sarcomatoid differentiation. Higher magnification detailing nests of basal cell carcinoma surrounded by hypercellular sarcomatoid stroma, which includes atypical plump and spindle cells in a fibromyxoid background.

Q: Clinically, Superficial Basal Cell Carcinoma often presents as an erythematous, mildly scaly patch with characteristic [...].
Superficial basal cell carcinoma. Superficial basal cell carcinoma presents as an erythematous patch, often with rolled borders and multifocal erosion.
A: rolled borders
Back Extra: Superficial Basal Cell Carcinoma
- Clinical: Superficial basal cell carcinoma presents as erythematous, often annular, mildly scaly patches with rolled borders, ranging from 1–2 mm to > 100 mm in diameter.
- Micro: Lobules of basaloid cells with peripheral palisading extend from the base of the epidermis into the papillary dermis. Retraction of lobules from surrounding fibromyxoid stroma and a lymphoplasmacytic infiltrate may be seen.
- Ancillary: BerEP4/EpCAM is positive in superficial basal cell carcinoma but negative in actinic keratosis.
Reference Gallery:
Superficial basal cell carcinoma. Superficial basal cell carcinoma presents as an erythematous patch, often with rolled borders and multifocal erosion.
Superficial basal cell carcinoma. Dermoscopy of superficial basal cell carcinoma shows chaotic pigmentation, multiple microulcerations, and white lines.
Superficial basal cell carcinoma. Superficial basal cell carcinoma showing multiple nests of basaloid epithelium emanating from dermoepidermal junction.
Superficial basal cell carcinoma. Nests of superficial basal cell carcinoma intermingled with a chronically inflamed, fibrotic-appearing dermis.

Q: Dermoscopy of Superficial Basal Cell Carcinoma characteristically reveals chaotic pigmentation, white lines, and multiple [...].
Superficial basal cell carcinoma. Dermoscopy of superficial basal cell carcinoma shows chaotic pigmentation, multiple microulcerations, and white lines.
A: microulcerations
Back Extra: Superficial Basal Cell Carcinoma
- Clinical: Superficial basal cell carcinoma presents as erythematous, often annular, mildly scaly patches with rolled borders, ranging from 1–2 mm to > 100 mm in diameter.
- Micro: Lobules of basaloid cells with peripheral palisading extend from the base of the epidermis into the papillary dermis. Retraction of lobules from surrounding fibromyxoid stroma and a lymphoplasmacytic infiltrate may be seen.
- Ancillary: BerEP4/EpCAM is positive in superficial basal cell carcinoma but negative in actinic keratosis.
Reference Gallery:
Superficial basal cell carcinoma. Superficial basal cell carcinoma presents as an erythematous patch, often with rolled borders and multifocal erosion.
Superficial basal cell carcinoma. Dermoscopy of superficial basal cell carcinoma shows chaotic pigmentation, multiple microulcerations, and white lines.
Superficial basal cell carcinoma. Superficial basal cell carcinoma showing multiple nests of basaloid epithelium emanating from dermoepidermal junction.
Superficial basal cell carcinoma. Nests of superficial basal cell carcinoma intermingled with a chronically inflamed, fibrotic-appearing dermis.

Q: The defining histologic feature of Superficial Basal Cell Carcinoma consists of multifocal nests of basaloid epithelium with peripheral palisading that emanate directly from the [...].
Superficial basal cell carcinoma. Superficial basal cell carcinoma showing multiple nests of basaloid epithelium emanating from dermoepidermal junction.
Superficial basal cell carcinoma. Nests of superficial basal cell carcinoma intermingled with a chronically inflamed, fibrotic-appearing dermis.
A: dermoepidermal junction
Back Extra: Superficial Basal Cell Carcinoma
- Clinical: Superficial basal cell carcinoma presents as erythematous, often annular, mildly scaly patches with rolled borders, ranging from 1–2 mm to > 100 mm in diameter.
- Micro: Lobules of basaloid cells with peripheral palisading extend from the base of the epidermis into the papillary dermis. Retraction of lobules from surrounding fibromyxoid stroma and a lymphoplasmacytic infiltrate may be seen.
- Ancillary: BerEP4/EpCAM is positive in superficial basal cell carcinoma but negative in actinic keratosis.
Reference Gallery:
Superficial basal cell carcinoma. Superficial basal cell carcinoma presents as an erythematous patch, often with rolled borders and multifocal erosion.
Superficial basal cell carcinoma. Dermoscopy of superficial basal cell carcinoma shows chaotic pigmentation, multiple microulcerations, and white lines.
Superficial basal cell carcinoma. Superficial basal cell carcinoma showing multiple nests of basaloid epithelium emanating from dermoepidermal junction.
Superficial basal cell carcinoma. Nests of superficial basal cell carcinoma intermingled with a chronically inflamed, fibrotic-appearing dermis.

Q: Histologically, Basosquamous Carcinoma is characterized by areas of malignant squamous epithelium intermingled with [...] areas, characteristically exhibiting a transition zone between the two morphologic patterns.
Basosquamous carcinoma. Basaloid areas (upper portion of the field) intermingled with areas of malignant squamous epithelium (lower portion of the field).
A: basaloid
Back Extra: Basosquamous Carcinoma
- Clinical: Patients with Basosquamous Carcinoma often present with a slowly evolving papule or nodule, frequently ulcerated, and dermoscopic features that show combined characteristics of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
- Micro: Histologically, Basosquamous Carcinoma shows distinct zones of basaloid cell growth (BCC) intermixed with squamous cell carcinoma (SCC), often with a zone of transition between the two.
- Ancillary: Immunohistochemical stains such as BerEP4 and EMA are helpful to demonstrate the transition zone between basaloid and squamous morphologies.
Reference Gallery:
Basosquamous carcinoma. Basaloid areas (upper portion of the field) intermingled with areas of malignant squamous epithelium (lower portion of the field).

Q: In Basosquamous Carcinoma, distinct zones of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are present, typically demonstrating a [...] where the two morphologies intermix.
Basosquamous carcinoma. Basaloid areas (upper portion of the field) intermingled with areas of malignant squamous epithelium (lower portion of the field).
A: transition zone
Back Extra: Basosquamous Carcinoma
- Clinical: Patients with Basosquamous Carcinoma often present with a slowly evolving papule or nodule, frequently ulcerated, and dermoscopic features that show combined characteristics of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
- Micro: Histologically, Basosquamous Carcinoma shows distinct zones of basaloid cell growth (BCC) intermixed with squamous cell carcinoma (SCC), often with a zone of transition between the two.
- Ancillary: Immunohistochemical stains such as BerEP4 and EMA are helpful to demonstrate the transition zone between basaloid and squamous morphologies.
Reference Gallery:
Basosquamous carcinoma. Basaloid areas (upper portion of the field) intermingled with areas of malignant squamous epithelium (lower portion of the field).

Q: Clinically, a Keratoacanthoma is a rapidly growing squamous tumor that classically presents with a central keratotic plug and uniquely undergoes spontaneous [...] within a year.
Keratoacanthoma. A young man presented with a rapidly growing, smooth-surfaced nodule with keratotic centre typical for a keratoacanthoma on the nasal alar. His father died at a young age from colorectal carcinoma, and a paternal cousin has Muir–Torre syndrome.
A: regression
Back Extra: Keratoacanthoma
- Clinical: Keratoacanthoma is a self-limiting squamous tumour characterized by rapid growth, stabilization, and spontaneous regression within a year.
- Micro: Histologically, keratoacanthoma shows a central keratin-filled crater with overhanging lips of normal epidermis and a peripheral graded pattern of p53 and Ki-67 expression.
- Ancillary: Keratoacanthomas may display RAS driver mutations in 10-40% of cases, and TGFBR1 mutations are found in the Ferguson–Smith type.
Reference Gallery:
Keratoacanthoma. A young man presented with a rapidly growing, smooth-surfaced nodule with keratotic centre typical for a keratoacanthoma on the nasal alar. His father died at a young age from colorectal carcinoma, and a paternal cousin has Muir–Torre syndrome.
Keratoacanthoma. Good cosmetic result 2 years after shave removal and watchful waiting (see <<34982>> to see initial appearance).
Keratoacanthoma. Shave biopsy showing a relatively symmetrical, exoendophytic lesion with central keratin-filled crater with overhanging lips of normal epidermis.
Keratoacanthoma. Predominant compact orthokeratin of trichilemmal type surrounded by cells with characteristic abundant glassy eosinophilic cytoplasm. Central well-formed neutrophil microabscess.
Keratoacanthoma. The tumour is wrapped around a small nerve in the base of the biopsy. The peripheral (basal) cells retain a normal N:C ratio. Cellular atypia is mild.
Keratoacanthoma. Typical mosaic pattern of p16 expression by immunohistochemistry.
Keratoacanthoma. Peripheral graded pattern of p53 expression by immunohistochemistry.
Keratoacanthoma. Ki-67 showing a peripheral-only pattern, which is congruent with the pattern on p53 immunohistochemistry. This combination is typical for keratoacanthoma and uncommon in cutaneous squamous cell carcinoma, keratoacanthoma-like.
Keratoacanthoma. Clinical history: 79-year-old woman, nodule on shin, suspicious for keratoacanthoma or squamous cell carcinoma. Punch biopsy shows part of a well-formed crater with predominant laminated orthokeratosis forming rounded infundibular-type structures.
Keratoacanthoma. Deeper part shows nodules comprising the characteristic keratinocytes with abundant glassy cytoplasm and typical trichilemmal pattern of keratinization; parakeratosis is slight, without hyperchromatic crowded nuclei.
Keratoacanthoma. Cellular pleomorphism is mild to moderate, but cells retain a normal N:C ratio, and such large nuclei may be due to hyperdiploid cells (note multinucleated cell on the right). The lesion lacks the thick proliferative zone, high N:C ratio, and acantholysis that characterize squamous cell carcinoma.
Keratoacanthoma. Clinical image. After 4 months of watchful waiting, the lesion was stable in size but had not resolved, and lesion was excised with clear margins.

Q: At low magnification, the classic histologic architecture of a Keratoacanthoma consists of a central keratin-filled crater flanked by [...] of normal epidermis.
Keratoacanthoma. Shave biopsy showing a relatively symmetrical, exoendophytic lesion with central keratin-filled crater with overhanging lips of normal epidermis.
A: overhanging lips
Back Extra: Keratoacanthoma
- Clinical: Keratoacanthoma is a self-limiting squamous tumour characterized by rapid growth, stabilization, and spontaneous regression within a year.
- Micro: Histologically, keratoacanthoma shows a central keratin-filled crater with overhanging lips of normal epidermis and a peripheral graded pattern of p53 and Ki-67 expression.
- Ancillary: Keratoacanthomas may display RAS driver mutations in 10-40% of cases, and TGFBR1 mutations are found in the Ferguson–Smith type.
Reference Gallery:
Keratoacanthoma. A young man presented with a rapidly growing, smooth-surfaced nodule with keratotic centre typical for a keratoacanthoma on the nasal alar. His father died at a young age from colorectal carcinoma, and a paternal cousin has Muir–Torre syndrome.
Keratoacanthoma. Good cosmetic result 2 years after shave removal and watchful waiting (see <<34982>> to see initial appearance).
Keratoacanthoma. Shave biopsy showing a relatively symmetrical, exoendophytic lesion with central keratin-filled crater with overhanging lips of normal epidermis.
Keratoacanthoma. Predominant compact orthokeratin of trichilemmal type surrounded by cells with characteristic abundant glassy eosinophilic cytoplasm. Central well-formed neutrophil microabscess.
Keratoacanthoma. The tumour is wrapped around a small nerve in the base of the biopsy. The peripheral (basal) cells retain a normal N:C ratio. Cellular atypia is mild.
Keratoacanthoma. Typical mosaic pattern of p16 expression by immunohistochemistry.
Keratoacanthoma. Peripheral graded pattern of p53 expression by immunohistochemistry.
Keratoacanthoma. Ki-67 showing a peripheral-only pattern, which is congruent with the pattern on p53 immunohistochemistry. This combination is typical for keratoacanthoma and uncommon in cutaneous squamous cell carcinoma, keratoacanthoma-like.
Keratoacanthoma. Clinical history: 79-year-old woman, nodule on shin, suspicious for keratoacanthoma or squamous cell carcinoma. Punch biopsy shows part of a well-formed crater with predominant laminated orthokeratosis forming rounded infundibular-type structures.
Keratoacanthoma. Deeper part shows nodules comprising the characteristic keratinocytes with abundant glassy cytoplasm and typical trichilemmal pattern of keratinization; parakeratosis is slight, without hyperchromatic crowded nuclei.
Keratoacanthoma. Cellular pleomorphism is mild to moderate, but cells retain a normal N:C ratio, and such large nuclei may be due to hyperdiploid cells (note multinucleated cell on the right). The lesion lacks the thick proliferative zone, high N:C ratio, and acantholysis that characterize squamous cell carcinoma.
Keratoacanthoma. Clinical image. After 4 months of watchful waiting, the lesion was stable in size but had not resolved, and lesion was excised with clear margins.

Q: Immunohistochemical staining for p53 and Ki-67 in a Keratoacanthoma characteristically displays a graded, strictly [...] pattern of expression, helping distinguish it from conventional squamous cell carcinoma.
Keratoacanthoma. Peripheral graded pattern of p53 expression by immunohistochemistry.
Keratoacanthoma. Ki-67 showing a peripheral-only pattern, which is congruent with the pattern on p53 immunohistochemistry. This combination is typical for keratoacanthoma and uncommon in cutaneous squamous cell carcinoma, keratoacanthoma-like.
A: peripheral
Back Extra: Keratoacanthoma
- Clinical: Keratoacanthoma is a self-limiting squamous tumour characterized by rapid growth, stabilization, and spontaneous regression within a year.
- Micro: Histologically, keratoacanthoma shows a central keratin-filled crater with overhanging lips of normal epidermis and a peripheral graded pattern of p53 and Ki-67 expression.
- Ancillary: Keratoacanthomas may display RAS driver mutations in 10-40% of cases, and TGFBR1 mutations are found in the Ferguson–Smith type.
Reference Gallery:
Keratoacanthoma. A young man presented with a rapidly growing, smooth-surfaced nodule with keratotic centre typical for a keratoacanthoma on the nasal alar. His father died at a young age from colorectal carcinoma, and a paternal cousin has Muir–Torre syndrome.
Keratoacanthoma. Good cosmetic result 2 years after shave removal and watchful waiting (see <<34982>> to see initial appearance).
Keratoacanthoma. Shave biopsy showing a relatively symmetrical, exoendophytic lesion with central keratin-filled crater with overhanging lips of normal epidermis.
Keratoacanthoma. Predominant compact orthokeratin of trichilemmal type surrounded by cells with characteristic abundant glassy eosinophilic cytoplasm. Central well-formed neutrophil microabscess.
Keratoacanthoma. The tumour is wrapped around a small nerve in the base of the biopsy. The peripheral (basal) cells retain a normal N:C ratio. Cellular atypia is mild.
Keratoacanthoma. Typical mosaic pattern of p16 expression by immunohistochemistry.
Keratoacanthoma. Peripheral graded pattern of p53 expression by immunohistochemistry.
Keratoacanthoma. Ki-67 showing a peripheral-only pattern, which is congruent with the pattern on p53 immunohistochemistry. This combination is typical for keratoacanthoma and uncommon in cutaneous squamous cell carcinoma, keratoacanthoma-like.
Keratoacanthoma. Clinical history: 79-year-old woman, nodule on shin, suspicious for keratoacanthoma or squamous cell carcinoma. Punch biopsy shows part of a well-formed crater with predominant laminated orthokeratosis forming rounded infundibular-type structures.
Keratoacanthoma. Deeper part shows nodules comprising the characteristic keratinocytes with abundant glassy cytoplasm and typical trichilemmal pattern of keratinization; parakeratosis is slight, without hyperchromatic crowded nuclei.
Keratoacanthoma. Cellular pleomorphism is mild to moderate, but cells retain a normal N:C ratio, and such large nuclei may be due to hyperdiploid cells (note multinucleated cell on the right). The lesion lacks the thick proliferative zone, high N:C ratio, and acantholysis that characterize squamous cell carcinoma.
Keratoacanthoma. Clinical image. After 4 months of watchful waiting, the lesion was stable in size but had not resolved, and lesion was excised with clear margins.

Q: A rare, rapidly growing variant of squamous cell carcinoma characterized by poorly differentiated tumor cell islands embedded within and obscured by a dense inflammatory infiltrate is known as [...].
Lymphoepithelial carcinoma. Poorly differentiated tumour cell islands surrounded and infiltrated by a heavy inflammatory infiltrate.
Lymphoepithelial carcinoma. The tumour consists of numerous lymphocytes, scattered multinucleated giant cells, and plasma cells, in which malignant infiltrative squamous epithelial elements are embedded.
A: Lymphoepithelial Carcinoma
Back Extra: Lymphoepithelial Carcinoma
- Clinical: Lymphoepithelial carcinoma of the skin is a rare, rapidly growing SCC that typically involves sun-exposed areas, especially the head and neck.
- Micro: Characterized by poorly differentiated tumour cell islands surrounded by a dense lymphoplasmacytic infiltrate, resembling undifferentiated nasopharyngeal carcinoma.
- Ancillary: Immunohistochemistry (pancytokeratin, CK5/6, or p63) confirms the presence of epithelial elements, which may be obscured by the lymphoid component.
Reference Gallery:
Lymphoepithelial carcinoma. Poorly differentiated tumour cell islands surrounded and infiltrated by a heavy inflammatory infiltrate.
Lymphoepithelial carcinoma. The tumour consists of numerous lymphocytes, scattered multinucleated giant cells, and plasma cells, in which malignant infiltrative squamous epithelial elements are embedded.

Q: Microscopically, the malignant squamous epithelial elements in Lymphoepithelial Carcinoma are characteristically obscured by a dense [...] infiltrate.
Lymphoepithelial carcinoma. Poorly differentiated tumour cell islands surrounded and infiltrated by a heavy inflammatory infiltrate.
Lymphoepithelial carcinoma. The tumour consists of numerous lymphocytes, scattered multinucleated giant cells, and plasma cells, in which malignant infiltrative squamous epithelial elements are embedded.
A: lymphoplasmacytic
Back Extra: Lymphoepithelial Carcinoma
- Clinical: Lymphoepithelial carcinoma of the skin is a rare, rapidly growing SCC that typically involves sun-exposed areas, especially the head and neck.
- Micro: Characterized by poorly differentiated tumour cell islands surrounded by a dense lymphoplasmacytic infiltrate, resembling undifferentiated nasopharyngeal carcinoma.
- Ancillary: Immunohistochemistry (pancytokeratin, CK5/6, or p63) confirms the presence of epithelial elements, which may be obscured by the lymphoid component.
Reference Gallery:
Lymphoepithelial carcinoma. Poorly differentiated tumour cell islands surrounded and infiltrated by a heavy inflammatory infiltrate.
Lymphoepithelial carcinoma. The tumour consists of numerous lymphocytes, scattered multinucleated giant cells, and plasma cells, in which malignant infiltrative squamous epithelial elements are embedded.

Q: The hallmark microscopic finding in Acantholytic Squamous Cell Carcinoma is the presence of [...] within the tumor nests, which can mimic glandular or vascular structures.
Acantholytic squamous cell carcinoma. At low magnification, acantholytic spaces are visible within much of the tumour.
Acantholytic squamous cell carcinoma. There is prominent acantholysis within many of the nests of invasive squamous cells.
A: acantholytic spaces
Back Extra: Acantholytic Squamous Cell Carcinoma
- Clinical: Acantholytic Squamous Cell Carcinoma (SCC) often presents on the head, neck, face, and ears, with older men and organ transplant recipients being at higher risk.
- Micro: The hallmark of acantholytic SCC is the presence of acantholytic spaces within the tumour nests, resulting from impaired intercellular adhesion and cell separation.
- Ancillary: Immunohistochemically, pseudoglandular spaces in acantholytic SCC are negative for mucin, CK7, and CEA, while pseudovascular regions are negative for CD31 and ERG.
Reference Gallery:
Acantholytic squamous cell carcinoma. At low magnification, acantholytic spaces are visible within much of the tumour.
Acantholytic squamous cell carcinoma. There is prominent acantholysis within many of the nests of invasive squamous cells.

Q: The distinctive spaces seen in the tumor nests of Acantholytic Squamous Cell Carcinoma are fundamentally caused by impaired [...] leading to cell separation.
Acantholytic squamous cell carcinoma. There is prominent acantholysis within many of the nests of invasive squamous cells.
A: intercellular adhesion
Back Extra: Acantholytic Squamous Cell Carcinoma
- Clinical: Acantholytic Squamous Cell Carcinoma (SCC) often presents on the head, neck, face, and ears, with older men and organ transplant recipients being at higher risk.
- Micro: The hallmark of acantholytic SCC is the presence of acantholytic spaces within the tumour nests, resulting from impaired intercellular adhesion and cell separation.
- Ancillary: Immunohistochemically, pseudoglandular spaces in acantholytic SCC are negative for mucin, CK7, and CEA, while pseudovascular regions are negative for CD31 and ERG.
Reference Gallery:
Acantholytic squamous cell carcinoma. At low magnification, acantholytic spaces are visible within much of the tumour.
Acantholytic squamous cell carcinoma. There is prominent acantholysis within many of the nests of invasive squamous cells.

Q: In Clear Cell Squamous Cell Carcinoma, the malignant squamoid cells are characterized by prominent [...], which may occasionally result in the formation of signet-ring cells.
Clear cell squamous cell carcinoma. Cytoplasmic vacuolation is prominent in areas with some signet-ring cells.
A: cytoplasmic vacuolation
Back Extra: Clear Cell Squamous Cell Carcinoma
- Clinical: Clear cell squamous cell carcinoma often occurs on sun-damaged skin of older men, particularly affecting the head and neck.
- Micro: The tumour contains malignant squamoid clear epithelial cells with cytoplasmic vacuolation and focal keratinization. Intracytoplasmic vacuoles are typically unilocular, and the clear material is usually PAS-positive glycogen.
- Ancillary: Immunohistochemistry is similar to conventional SCC, with BerEP4 being negative. Glycogen accumulation in the cytoplasm of the neoplastic cells is PAS-positive.
Reference Gallery:
Clear cell squamous cell carcinoma. Cytoplasmic vacuolation is prominent in areas with some signet-ring cells.
Clear cell squamous cell carcinoma. The cells have glycogen-rich cytoplasm and give a positive PAS reaction.

Q: The clear material within the neoplastic cells of Clear Cell Squamous Cell Carcinoma is typically glycogen, which is highlighted by a positive [...] stain.
Clear cell squamous cell carcinoma. The cells have glycogen-rich cytoplasm and give a positive PAS reaction.
A: periodic acid-Schiff (PAS)
Back Extra: Clear Cell Squamous Cell Carcinoma
- Clinical: Clear cell squamous cell carcinoma often occurs on sun-damaged skin of older men, particularly affecting the head and neck.
- Micro: The tumour contains malignant squamoid clear epithelial cells with cytoplasmic vacuolation and focal keratinization. Intracytoplasmic vacuoles are typically unilocular, and the clear material is usually PAS-positive glycogen.
- Ancillary: Immunohistochemistry is similar to conventional SCC, with BerEP4 being negative. Glycogen accumulation in the cytoplasm of the neoplastic cells is PAS-positive.
Reference Gallery:
Clear cell squamous cell carcinoma. Cytoplasmic vacuolation is prominent in areas with some signet-ring cells.
Clear cell squamous cell carcinoma. The cells have glycogen-rich cytoplasm and give a positive PAS reaction.

Q: Clinically, Squamous Cell Carcinoma commonly arises in chronically sun-damaged skin, presenting as a red scaly plaque that progresses to a characteristic, often ulcerated, [...] nodule.
Squamous cell carcinoma. Clinical appearance of typical invasive squamous cell carcinoma forming a nodule surmounted by hyperkeratotic scale, arising in chronically sun-damaged skin.
A: hyperkeratotic
Back Extra: Squamous Cell Carcinoma
- Clinical: Squamous cell carcinoma appears as a solitary red scaly plaque, progressing to a hyperkeratotic, often ulcerated nodule. Regional lymph node involvement is the first route of metastasis.
- Micro: Invasive SCC shows polygonal cellular profiles, pleomorphism, and varying amounts of cytoplasmic and extracytoplasmic keratin. Most are well to moderately differentiated.
- Ancillary: Common mutations involve tumour suppressor genes such as TP53, NOTCH1, and NOTCH2. UV radiation–induced TP53 mutations occur early in the process.
Reference Gallery:
Squamous cell carcinoma. Clinical appearance of typical invasive squamous cell carcinoma forming a nodule surmounted by hyperkeratotic scale, arising in chronically sun-damaged skin.

Q: Histologically, Spindle Cell Squamous Cell Carcinoma is characterized by closely packed fascicles of pleomorphic spindle cells, often demonstrating a transition from vaguely nested [...] cells.
Spindle squamous cell carcinoma. Epithelioid, vaguely nested cells in transition to a fusiform elongated spindled morphology.
Spindle cell squamous cell carcinoma. Closely packed pleomorphic spindle cells.
A: epithelioid
Back Extra: Spindle Cell Squamous Cell Carcinoma
- Clinical: Spindle cell squamous cell carcinoma (SCC) typically arises in sun-exposed areas, presenting as a raised or exophytic plaque, nodule, or tumour, often with bleeding or ulceration.
- Micro: Histologically, spindle cell SCC is characterized by closely packed fascicles of pleomorphic spindle cells, often with mitotic activity and a background of actinic keratosis or SCC in situ.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with positive staining for p63, p40, 34βE12, CK5/6, and/or MNF116, especially if no epithelioid squamous component is present.
Reference Gallery:
Spindle cell squamous cell carcinoma occurring as a nodule on the arm
Spindle cell squamous cell carcinoma. Note the edge of a tumour nodule with marked solar elastosis.
Spindle squamous cell carcinoma. Epithelioid, vaguely nested cells in transition to a fusiform elongated spindled morphology.
Spindle cell squamous cell carcinoma. Closely packed pleomorphic spindle cells.
Spindle cell squamous cell carcinoma. Pancytokeratin immunostaining is positive in scattered lesional cells.

Q: Immunohistochemical evaluation of Spindle Cell Squamous Cell Carcinoma is crucial when a conventional squamous component is absent, typically demonstrating scattered lesional cell positivity for p63, p40, and [...].
Spindle cell squamous cell carcinoma. Pancytokeratin immunostaining is positive in scattered lesional cells.
A: pancytokeratin
Back Extra: Spindle Cell Squamous Cell Carcinoma
- Clinical: Spindle cell squamous cell carcinoma (SCC) typically arises in sun-exposed areas, presenting as a raised or exophytic plaque, nodule, or tumour, often with bleeding or ulceration.
- Micro: Histologically, spindle cell SCC is characterized by closely packed fascicles of pleomorphic spindle cells, often with mitotic activity and a background of actinic keratosis or SCC in situ.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with positive staining for p63, p40, 34βE12, CK5/6, and/or MNF116, especially if no epithelioid squamous component is present.
Reference Gallery:
Spindle cell squamous cell carcinoma occurring as a nodule on the arm
Spindle cell squamous cell carcinoma. Note the edge of a tumour nodule with marked solar elastosis.
Spindle squamous cell carcinoma. Epithelioid, vaguely nested cells in transition to a fusiform elongated spindled morphology.
Spindle cell squamous cell carcinoma. Closely packed pleomorphic spindle cells.
Spindle cell squamous cell carcinoma. Pancytokeratin immunostaining is positive in scattered lesional cells.

Q: Clinically and histologically, Spindle Cell Squamous Cell Carcinoma typically arises on heavily sun-exposed skin, frequently presenting as a nodule or tumor with an adjacent dermal background of marked [...].
Spindle cell squamous cell carcinoma occurring as a nodule on the arm
Spindle cell squamous cell carcinoma. Note the edge of a tumour nodule with marked solar elastosis.
A: solar elastosis
Back Extra: Spindle Cell Squamous Cell Carcinoma
- Clinical: Spindle cell squamous cell carcinoma (SCC) typically arises in sun-exposed areas, presenting as a raised or exophytic plaque, nodule, or tumour, often with bleeding or ulceration.
- Micro: Histologically, spindle cell SCC is characterized by closely packed fascicles of pleomorphic spindle cells, often with mitotic activity and a background of actinic keratosis or SCC in situ.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with positive staining for p63, p40, 34βE12, CK5/6, and/or MNF116, especially if no epithelioid squamous component is present.
Reference Gallery:
Spindle cell squamous cell carcinoma occurring as a nodule on the arm
Spindle cell squamous cell carcinoma. Note the edge of a tumour nodule with marked solar elastosis.
Spindle squamous cell carcinoma. Epithelioid, vaguely nested cells in transition to a fusiform elongated spindled morphology.
Spindle cell squamous cell carcinoma. Closely packed pleomorphic spindle cells.
Spindle cell squamous cell carcinoma. Pancytokeratin immunostaining is positive in scattered lesional cells.

Q: Spindle Cell Squamous Cell Carcinoma is histologically characterized by closely packed fascicles of pleomorphic spindle cells, typically arising in a background of severe [...].
Spindle cell squamous cell carcinoma. Note the edge of a tumour nodule with marked solar elastosis.
Spindle cell squamous cell carcinoma. Closely packed pleomorphic spindle cells.
A: solar elastosis
Back Extra: Spindle Cell Squamous Cell Carcinoma
- Clinical: Spindle cell squamous cell carcinoma often presents as a raised or exophytic plaque, nodule, or tumour, with symptoms of bleeding, ulceration, and rapid growth.
- Micro: The tumour is composed of closely packed fascicles of pleomorphic spindle cells, typically in a background of severe solar elastosis, with frequent mitotic activity.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with positive staining for p63, p40, 34βE12, CK5/6, and/or MNF116.
Reference Gallery:
Diagnosis not found. Legend text not found
Spindle cell squamous cell carcinoma. Note the edge of a tumour nodule with marked solar elastosis.
Spindle squamous cell carcinoma. Epithelioid, vaguely nested cells in transition to a fusiform elongated spindled morphology.
Spindle cell squamous cell carcinoma. Closely packed pleomorphic spindle cells.
Spindle cell squamous cell carcinoma. Pancytokeratin immunostaining is positive in scattered lesional cells.

Q: Spindle Cell Squamous Cell Carcinoma frequently displays an architectural transition from vaguely nested [...] cells into an elongated, fusiform spindled morphology.
Spindle squamous cell carcinoma. Epithelioid, vaguely nested cells in transition to a fusiform elongated spindled morphology.
A: epithelioid
Back Extra: Spindle Cell Squamous Cell Carcinoma
- Clinical: Spindle cell squamous cell carcinoma often presents as a raised or exophytic plaque, nodule, or tumour, with symptoms of bleeding, ulceration, and rapid growth.
- Micro: The tumour is composed of closely packed fascicles of pleomorphic spindle cells, typically in a background of severe solar elastosis, with frequent mitotic activity.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with positive staining for p63, p40, 34βE12, CK5/6, and/or MNF116.
Reference Gallery:
Diagnosis not found. Legend text not found
Spindle cell squamous cell carcinoma. Note the edge of a tumour nodule with marked solar elastosis.
Spindle squamous cell carcinoma. Epithelioid, vaguely nested cells in transition to a fusiform elongated spindled morphology.
Spindle cell squamous cell carcinoma. Closely packed pleomorphic spindle cells.
Spindle cell squamous cell carcinoma. Pancytokeratin immunostaining is positive in scattered lesional cells.

Q: Spindle Cell Squamous Cell Carcinoma can be confirmed via immunohistochemistry, typically demonstrating positivity in scattered tumor cells for squamous markers (e.g., p63, p40) and broad epithelial markers like [...].
Spindle cell squamous cell carcinoma. Pancytokeratin immunostaining is positive in scattered lesional cells.
A: pancytokeratin
Back Extra: Spindle Cell Squamous Cell Carcinoma
- Clinical: Spindle cell squamous cell carcinoma often presents as a raised or exophytic plaque, nodule, or tumour, with symptoms of bleeding, ulceration, and rapid growth.
- Micro: The tumour is composed of closely packed fascicles of pleomorphic spindle cells, typically in a background of severe solar elastosis, with frequent mitotic activity.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with positive staining for p63, p40, 34βE12, CK5/6, and/or MNF116.
Reference Gallery:
Diagnosis not found. Legend text not found
Spindle cell squamous cell carcinoma. Note the edge of a tumour nodule with marked solar elastosis.
Spindle squamous cell carcinoma. Epithelioid, vaguely nested cells in transition to a fusiform elongated spindled morphology.
Spindle cell squamous cell carcinoma. Closely packed pleomorphic spindle cells.
Spindle cell squamous cell carcinoma. Pancytokeratin immunostaining is positive in scattered lesional cells.

Q: Verrucous Squamous Cell Carcinoma is histologically characterized by a complex exophytic and endophytic architecture featuring deep, [...] tongues of well-differentiated squamous epithelium.
Verrucous squamous cell carcinoma. Scanning magnification shows a well-differentiated, keratinizing field giving rise to exuberant hyperkeratosis; the endophytic component forms invasive tongues with a characteristic club-shaped architecture.
A: club-shaped
Back Extra: Verrucous Squamous Cell Carcinoma
- Clinical: Verrucous squamous cell carcinoma can present as hyperkeratotic plaques on the palms and soles, which may be mistaken for verrucae or callosities.
- Micro: Characterized by a complex exophytic and endophytic architecture with deep, club-shaped tongues of intradermal growth and minimal cytological atypia.
- Ancillary: Overexpression of MDM2, a negative regulator of p53, has been implicated in the pathogenesis of verrucous squamous cell carcinoma.
Reference Gallery:
Verrucous squamous cell carcinoma. Scanning magnification shows a well-differentiated, keratinizing field giving rise to exuberant hyperkeratosis; the endophytic component forms invasive tongues with a characteristic club-shaped architecture.
Verrucous squamous cell carcinoma. The epithelial–stromal interface is mostly smooth but focally irregularly contoured.

Q: Unlike conventional variants, Verrucous Squamous Cell Carcinoma typically displays an epithelial–stromal interface that is mostly [...], representing a broad and blunt "pushing" border rather than an infiltrative one.
Verrucous squamous cell carcinoma. The epithelial–stromal interface is mostly smooth but focally irregularly contoured.
A: smooth
Back Extra: Verrucous Squamous Cell Carcinoma
- Clinical: Verrucous squamous cell carcinoma can present as hyperkeratotic plaques on the palms and soles, which may be mistaken for verrucae or callosities.
- Micro: Characterized by a complex exophytic and endophytic architecture with deep, club-shaped tongues of intradermal growth and minimal cytological atypia.
- Ancillary: Overexpression of MDM2, a negative regulator of p53, has been implicated in the pathogenesis of verrucous squamous cell carcinoma.
Reference Gallery:
Verrucous squamous cell carcinoma. Scanning magnification shows a well-differentiated, keratinizing field giving rise to exuberant hyperkeratosis; the endophytic component forms invasive tongues with a characteristic club-shaped architecture.
Verrucous squamous cell carcinoma. The epithelial–stromal interface is mostly smooth but focally irregularly contoured.

Q: A biopsy of a scaly erythematous patch on a sun-exposed area reveals non-full-thickness squamous dysplasia affecting the basal to mid-spinous layers with overlying parakeratosis. These findings are diagnostic of [...].
Actinic keratosis. Clinical appearance of scaly erythematous patches on the face.
Actinic keratosis. Squamous dysplasia affecting the lower and middle epidermal layers with overlying parakeratosis on a background of sun-damaged skin.
Actinic keratosis. Higher-power magnification highlighting the non–full-thickness squamous dysplasia and overlying parakeratosis.
A: Actinic Keratosis
Back Extra: Actinic Keratosis
- Clinical: Actinic keratoses (AKs) typically present as scaly erythematous patches on sun-exposed skin.
- Micro: AKs show squamous dysplasia affecting the basal to mid-spinous layers with overlying parakeratosis and a background of solar elastosis.
- Ancillary: Not relevant
Reference Gallery:
Actinic keratosis. Squamous dysplasia affecting the lower and middle epidermal layers with overlying parakeratosis on a background of sun-damaged skin.
Actinic keratosis. Higher-power magnification highlighting the non–full-thickness squamous dysplasia and overlying parakeratosis.
Hypertrophic actinic keratosis. The hypertrophic subtype is characterized by verrucoid epidermal hyperplasia with massive overlying parakeratosis.
Proliferative actinic keratosis. The proliferative subtype shows prominent buds of dysplastic epidermis protruding into superficial dermis.
Actinic keratosis, acantholytic pattern. Acantholysis is a commonly seen feature in actinic keratoses.
Pigmented actinic keratosis. The pigmented subtype is characterized by cytoplasmic melanin pigmentation of the basal cell layer dysplastic keratinocytes.
Pigmented actinic keratosis. Melan-A immunohistochemistry highlights increased numbers of single junctional melanocytes, but there is no confluent growth of melanocytes excluding lentigo maligna.
Actinic keratosis. Clinical appearance of scaly erythematous patches on the face.

Q: Histologically, Actinic Keratosis typically arises on a background of chronically sun-damaged skin, which manifests as a basophilic degeneration of dermal collagen known as [...].
Actinic keratosis. Squamous dysplasia affecting the lower and middle epidermal layers with overlying parakeratosis on a background of sun-damaged skin.
A: solar elastosis
Back Extra: Actinic Keratosis
- Clinical: Actinic keratoses (AKs) typically present as scaly erythematous patches on sun-exposed skin.
- Micro: AKs show squamous dysplasia affecting the basal to mid-spinous layers with overlying parakeratosis and a background of solar elastosis.
- Ancillary: Not relevant
Reference Gallery:
Actinic keratosis. Squamous dysplasia affecting the lower and middle epidermal layers with overlying parakeratosis on a background of sun-damaged skin.
Actinic keratosis. Higher-power magnification highlighting the non–full-thickness squamous dysplasia and overlying parakeratosis.
Hypertrophic actinic keratosis. The hypertrophic subtype is characterized by verrucoid epidermal hyperplasia with massive overlying parakeratosis.
Proliferative actinic keratosis. The proliferative subtype shows prominent buds of dysplastic epidermis protruding into superficial dermis.
Actinic keratosis, acantholytic pattern. Acantholysis is a commonly seen feature in actinic keratoses.
Pigmented actinic keratosis. The pigmented subtype is characterized by cytoplasmic melanin pigmentation of the basal cell layer dysplastic keratinocytes.
Pigmented actinic keratosis. Melan-A immunohistochemistry highlights increased numbers of single junctional melanocytes, but there is no confluent growth of melanocytes excluding lentigo maligna.
Actinic keratosis. Clinical appearance of scaly erythematous patches on the face.

Q: The hypertrophic variant of Actinic Keratosis is histologically characterized by massive overlying parakeratosis and [...] epidermal hyperplasia.
Hypertrophic actinic keratosis. The hypertrophic subtype is characterized by verrucoid epidermal hyperplasia with massive overlying parakeratosis.
A: verrucoid
Back Extra: Actinic Keratosis
- Clinical: Actinic keratoses (AKs) typically present as scaly erythematous patches on sun-exposed skin.
- Micro: AKs show squamous dysplasia affecting the basal to mid-spinous layers with overlying parakeratosis and a background of solar elastosis.
- Ancillary: Not relevant
Reference Gallery:
Actinic keratosis. Squamous dysplasia affecting the lower and middle epidermal layers with overlying parakeratosis on a background of sun-damaged skin.
Actinic keratosis. Higher-power magnification highlighting the non–full-thickness squamous dysplasia and overlying parakeratosis.
Hypertrophic actinic keratosis. The hypertrophic subtype is characterized by verrucoid epidermal hyperplasia with massive overlying parakeratosis.
Proliferative actinic keratosis. The proliferative subtype shows prominent buds of dysplastic epidermis protruding into superficial dermis.
Actinic keratosis, acantholytic pattern. Acantholysis is a commonly seen feature in actinic keratoses.
Pigmented actinic keratosis. The pigmented subtype is characterized by cytoplasmic melanin pigmentation of the basal cell layer dysplastic keratinocytes.
Pigmented actinic keratosis. Melan-A immunohistochemistry highlights increased numbers of single junctional melanocytes, but there is no confluent growth of melanocytes excluding lentigo maligna.
Actinic keratosis. Clinical appearance of scaly erythematous patches on the face.

Q: Patients with a history of chronic heavy metal exposure may develop verrucous palmoplantar plaques; microscopic examination typically reveals hyperkeratosis and squamous dysplasia with prominent keratinocyte vacuolization, establishing a diagnosis of [...].
Arsenical keratosis. Almost full-thickness atypia of the epidermis, with dysregulated granular cell layer. Note the marked vacuolization of the cells, which is a helpful (although not diagnostic) feature.
Arsenical keratosis. Marked hyperkeratosis with a hyperplastic, highly dysregulated epidermis; there is slight papillomatosis.
Arsenical keratosis. Biopsy of the sole reveals basaloid hyperplasia with marked atypia, budding downward into the inflamed dermis. The lichenoid infiltrate is associated with apoptosis and clustered dyskeratosis of cells. Note that the overlying squamous cells are hyperplastic but without marked atypia.
A: Arsenical Keratosis
Back Extra: Arsenical Keratosis
- Clinical: Patients present with diffuse or localized hyperpigmentation and raindrop pigmentation affecting mainly the trunk, as well as yellowish hyperkeratotic papules and confluent verrucous plaques with a predilection for palmoplantar skin.
- Micro: Arsenical keratoses show a spectrum of morphology ranging from acanthosis, papillomatosis, and hyperkeratosis to squamous dysplasia, often with the dysplastic keratinocytes showing vacuolization, multinucleated forms, and atypical mitotic activity.
- Ancillary: Not relevant, but the history of chronic arsenic exposure and the characteristic clinical and histopathological features are key in distinguishing arsenical keratosis.
Reference Gallery:
Arsenical keratosis. Almost full-thickness atypia of the epidermis, with dysregulated granular cell layer. Note the marked vacuolization of the cells, which is a helpful (although not diagnostic) feature.
Arsenical keratosis. Marked hyperkeratosis with a hyperplastic, highly dysregulated epidermis; there is slight papillomatosis.
Arsenical keratosis. Biopsy of the sole reveals basaloid hyperplasia with marked atypia, budding downward into the inflamed dermis. The lichenoid infiltrate is associated with apoptosis and clustered dyskeratosis of cells. Note that the overlying squamous cells are hyperplastic but without marked atypia.

Q: A characteristic histologic feature of the dysplastic keratinocytes in Arsenical Keratosis is the presence of marked [...], which can be seen alongside multinucleated forms and atypical mitotic activity.
Arsenical keratosis. Almost full-thickness atypia of the epidermis, with dysregulated granular cell layer. Note the marked vacuolization of the cells, which is a helpful (although not diagnostic) feature.
A: vacuolization
Back Extra: Arsenical Keratosis
- Clinical: Patients present with diffuse or localized hyperpigmentation and raindrop pigmentation affecting mainly the trunk, as well as yellowish hyperkeratotic papules and confluent verrucous plaques with a predilection for palmoplantar skin.
- Micro: Arsenical keratoses show a spectrum of morphology ranging from acanthosis, papillomatosis, and hyperkeratosis to squamous dysplasia, often with the dysplastic keratinocytes showing vacuolization, multinucleated forms, and atypical mitotic activity.
- Ancillary: Not relevant, but the history of chronic arsenic exposure and the characteristic clinical and histopathological features are key in distinguishing arsenical keratosis.
Reference Gallery:
Arsenical keratosis. Almost full-thickness atypia of the epidermis, with dysregulated granular cell layer. Note the marked vacuolization of the cells, which is a helpful (although not diagnostic) feature.
Arsenical keratosis. Marked hyperkeratosis with a hyperplastic, highly dysregulated epidermis; there is slight papillomatosis.
Arsenical keratosis. Biopsy of the sole reveals basaloid hyperplasia with marked atypia, budding downward into the inflamed dermis. The lichenoid infiltrate is associated with apoptosis and clustered dyskeratosis of cells. Note that the overlying squamous cells are hyperplastic but without marked atypia.

Q: Histologically, Squamous Cell Carcinoma in Situ (Bowen Disease) is defined by the presence of [...] alongside acanthosis and parakeratotic hyperkeratosis, without dermal invasion.
Squamous cell carcinoma in situ (Bowen disease). There is full-thickness epidermal dysplasia associated with acanthosis and parakeratotic hyperkeratosis.
Squamous cell carcinoma in situ (Bowen disease). Full-thickness epidermal dysplasia is present; the superficial dermis shows severe solar elastosis and a patchy lymphocytic inflammatory cell infiltrate, but there is no dermal invasion.
Squamous cell carcinoma in situ (Bowen disease). Full-thickness epidermal dysplasia is present.
A: full-thickness epidermal dysplasia
Back Extra: Squamous Cell Carcinoma in Situ (Bowen Disease)
- Clinical: Patients with Squamous Cell Carcinoma in Situ (Bowen Disease) usually present with a solitary, slow-growing, scaly, erythematous patch or plaque, often on sun-exposed skin in elderly White patients.
- Micro: SCC in situ is characterized by full-thickness epidermal dysplasia with acanthosis, hyperparakeratosis, and a loss of the granular layer.
- Ancillary: TP53 mutations are found in the early stages of SCC in situ, and progression to invasive SCC is associated with immune dysregulation and increased PDL1 expression.
Reference Gallery:
Squamous cell carcinoma in situ (Bowen disease). There is full-thickness epidermal dysplasia associated with acanthosis and parakeratotic hyperkeratosis.
Squamous cell carcinoma in situ (Bowen disease). Full-thickness epidermal dysplasia is present; the superficial dermis shows severe solar elastosis and a patchy lymphocytic inflammatory cell infiltrate, but there is no dermal invasion.
Squamous cell carcinoma in situ (Bowen disease). Full-thickness epidermal dysplasia is present.
Squamous cell carcinoma in situ (Bowen disease). Bowen disease on chronically sun-damaged skin in the form of a red, scaly patch.
Squamous cell carcinoma in situ (Bowen disease). The corresponding dermoscopy of Bowen disease shown in <<37241>> is characterized by glomerular (coiled) vessels, scales, and a small erosion.
Squamous cell carcinoma in situ (Bowen disease). Low-power view of the dermatopathology of the case of Bowen disease shown in <<37241>> and <<37242>>, with acanthosis of the epidermis, hyperkeratosis and parakeratosis, full-thickness dysplasia, and a lymphocytic infiltrate.
Squamous cell carcinoma in situ (Bowen disease). High-power view of the dermatopathology of the case of Bowen disease shown in <<37241>> and <<37242>>, with acanthosis of the epidermis, hyperkeratosis and parakeratosis, full-thickness dysplasia, and a lymphocytic infiltrate.

Q: On dermoscopy, a scaly, erythematous patch of Squamous Cell Carcinoma in Situ (Bowen Disease) characteristically displays [...].
Squamous cell carcinoma in situ (Bowen disease). Bowen disease on chronically sun-damaged skin in the form of a red, scaly patch.
Squamous cell carcinoma in situ (Bowen disease). The corresponding dermoscopy of Bowen disease shown in <<37241>> is characterized by glomerular (coiled) vessels, scales, and a small erosion.
A: glomerular (coiled) vessels
Back Extra: Squamous Cell Carcinoma in Situ (Bowen Disease)
- Clinical: Patients with Squamous Cell Carcinoma in Situ (Bowen Disease) usually present with a solitary, slow-growing, scaly, erythematous patch or plaque, often on sun-exposed skin in elderly White patients.
- Micro: SCC in situ is characterized by full-thickness epidermal dysplasia with acanthosis, hyperparakeratosis, and a loss of the granular layer.
- Ancillary: TP53 mutations are found in the early stages of SCC in situ, and progression to invasive SCC is associated with immune dysregulation and increased PDL1 expression.
Reference Gallery:
Squamous cell carcinoma in situ (Bowen disease). There is full-thickness epidermal dysplasia associated with acanthosis and parakeratotic hyperkeratosis.
Squamous cell carcinoma in situ (Bowen disease). Full-thickness epidermal dysplasia is present; the superficial dermis shows severe solar elastosis and a patchy lymphocytic inflammatory cell infiltrate, but there is no dermal invasion.
Squamous cell carcinoma in situ (Bowen disease). Full-thickness epidermal dysplasia is present.
Squamous cell carcinoma in situ (Bowen disease). Bowen disease on chronically sun-damaged skin in the form of a red, scaly patch.
Squamous cell carcinoma in situ (Bowen disease). The corresponding dermoscopy of Bowen disease shown in <<37241>> is characterized by glomerular (coiled) vessels, scales, and a small erosion.
Squamous cell carcinoma in situ (Bowen disease). Low-power view of the dermatopathology of the case of Bowen disease shown in <<37241>> and <<37242>>, with acanthosis of the epidermis, hyperkeratosis and parakeratosis, full-thickness dysplasia, and a lymphocytic infiltrate.
Squamous cell carcinoma in situ (Bowen disease). High-power view of the dermatopathology of the case of Bowen disease shown in <<37241>> and <<37242>>, with acanthosis of the epidermis, hyperkeratosis and parakeratosis, full-thickness dysplasia, and a lymphocytic infiltrate.

Q: Clinically, PUVA Keratosis is characterized by multiple warty, hyperkeratotic papules that paradoxically arise on [...] skin, such as the trunk and thighs.
PUVA keratosis. Clinical appearance.
PUVA keratosis. Clinical appearance, close-up view.
A: sun-protected
Back Extra: PUVA Keratosis
- Clinical: PUVA keratosis presents with multiple warty, hyperkeratotic, and scaly papules on sun-protected skin, typically on the trunk and thighs.
- Micro: Histologically, PUVA keratosis is characterized by acanthosis, hyperkeratosis, and mild keratinocyte dysplasia in about 50% of cases.
- Ancillary: TP53 (57%) and HRAS (44%) mutations are frequently found, indicating UV radiation as a key etiological factor.
Reference Gallery:
PUVA keratosis. Hyperkeratosis with scattered parakeratosis. Note the effacement of the epidermal rete ridges, with atypia of the basal layer cells.
PUVA keratosis. Prominent atypia of the basal layer, with variably sized nuclei and focal squamatization. The squamous cells show dysmaturation with a variable increase in size and pallor; the granular cell layer is retained.
PUVA keratosis. Clinical appearance.
PUVA keratosis. Clinical appearance, close-up view.

Q: Histologically, PUVA Keratosis features hyperkeratosis, effaced epidermal rete ridges, and prominent cellular atypia that is characteristically localized to the [...] layer.
PUVA keratosis. Hyperkeratosis with scattered parakeratosis. Note the effacement of the epidermal rete ridges, with atypia of the basal layer cells.
PUVA keratosis. Prominent atypia of the basal layer, with variably sized nuclei and focal squamatization. The squamous cells show dysmaturation with a variable increase in size and pallor; the granular cell layer is retained.
A: basal
Back Extra: PUVA Keratosis
- Clinical: PUVA keratosis presents with multiple warty, hyperkeratotic, and scaly papules on sun-protected skin, typically on the trunk and thighs.
- Micro: Histologically, PUVA keratosis is characterized by acanthosis, hyperkeratosis, and mild keratinocyte dysplasia in about 50% of cases.
- Ancillary: TP53 (57%) and HRAS (44%) mutations are frequently found, indicating UV radiation as a key etiological factor.
Reference Gallery:
PUVA keratosis. Hyperkeratosis with scattered parakeratosis. Note the effacement of the epidermal rete ridges, with atypia of the basal layer cells.
PUVA keratosis. Prominent atypia of the basal layer, with variably sized nuclei and focal squamatization. The squamous cells show dysmaturation with a variable increase in size and pallor; the granular cell layer is retained.
PUVA keratosis. Clinical appearance.
PUVA keratosis. Clinical appearance, close-up view.

Q: Histologically, the atypical lymphoid cells of Adult T-cell leukaemia/lymphoma display marked nuclear pleomorphism with irregularly folded nuclei, and frequently aggregate within the epidermis to form [...].
Adult T-cell leukaemia/lymphoma involving skin. The epidermis and dermis show infiltration by atypical lymphoid cells with irregularly folded nuclei.
Adult T-cell leukaemia/lymphoma involving skin. In situ hybridization for HBZ, a viral transcript specific for HTLV-1. Positive signals (brown dots) are observed in the neoplastic cells forming a Pautrier microabscess.
A: Pautrier-like microabscesses
Back Extra: Adult T-cell leukaemia/lymphoma
- Clinical: Adult T-cell leukaemia/lymphoma often presents with skin lesions, including patch, plaque, multipapular, nodulotumoural, erythrodermic, and purpuric types.
- Micro: Histologically, the neoplastic cells form Pautrier-like microabscesses and show nuclear pleomorphism and mitotic activity.
- Ancillary: The neoplastic cells are positive for CD3, CD4, CD25, and CCR4, and negative for CD8, CD19, and CD20.
Reference Gallery:
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, patch type. The cutaneous manifestations of the patch/plaque and erythrodermic types share similarities with those of mycosis fungoides and Sézary syndrome, respectively.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, plaque type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, multipapular type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, nodulotumoural type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, erythrodermic type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, purpuric type.
Adult T-cell leukaemia/lymphoma involving skin. The epidermis and dermis show infiltration by atypical lymphoid cells with irregularly folded nuclei.
Adult T-cell leukaemia/lymphoma involving skin. The atypical lymphoid cells are immunoreactive for CD3.
Adult T-cell leukaemia/lymphoma involving skin. In situ hybridization for HBZ, a viral transcript specific for HTLV-1. Positive signals (brown dots) are observed in the neoplastic cells forming a Pautrier microabscess.
Adult T-cell leukaemia/lymphoma involving skin. The dermis is entirely involved by atypical lymphoid cells.
Adult T-cell leukaemia/lymphoma involving skin. The dermis is entirely involved by atypical lymphoid cells.
Adult T-cell leukaemia/lymphoma involving skin. The epidermis and dermis show infiltration by atypical lymphoid cells with irregularly folded nuclei.

Q: The cutaneous manifestations of the patch, plaque, and erythrodermic types of Adult T-cell leukaemia/lymphoma are highly variable and share clinical similarities with Sézary syndrome and [...].
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, patch type. The cutaneous manifestations of the patch/plaque and erythrodermic types share similarities with those of mycosis fungoides and Sézary syndrome, respectively.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, erythrodermic type.
A: mycosis fungoides
Back Extra: Adult T-cell leukaemia/lymphoma
- Clinical: Adult T-cell leukaemia/lymphoma often presents with skin lesions, including patch, plaque, multipapular, nodulotumoural, erythrodermic, and purpuric types.
- Micro: Histologically, the neoplastic cells form Pautrier-like microabscesses and show nuclear pleomorphism and mitotic activity.
- Ancillary: The neoplastic cells are positive for CD3, CD4, CD25, and CCR4, and negative for CD8, CD19, and CD20.
Reference Gallery:
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, patch type. The cutaneous manifestations of the patch/plaque and erythrodermic types share similarities with those of mycosis fungoides and Sézary syndrome, respectively.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, plaque type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, multipapular type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, nodulotumoural type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, erythrodermic type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, purpuric type.
Adult T-cell leukaemia/lymphoma involving skin. The epidermis and dermis show infiltration by atypical lymphoid cells with irregularly folded nuclei.
Adult T-cell leukaemia/lymphoma involving skin. The atypical lymphoid cells are immunoreactive for CD3.
Adult T-cell leukaemia/lymphoma involving skin. In situ hybridization for HBZ, a viral transcript specific for HTLV-1. Positive signals (brown dots) are observed in the neoplastic cells forming a Pautrier microabscess.
Adult T-cell leukaemia/lymphoma involving skin. The dermis is entirely involved by atypical lymphoid cells.
Adult T-cell leukaemia/lymphoma involving skin. The dermis is entirely involved by atypical lymphoid cells.
Adult T-cell leukaemia/lymphoma involving skin. The epidermis and dermis show infiltration by atypical lymphoid cells with irregularly folded nuclei.

Q: Adult T-cell leukaemia/lymphoma is etiologically driven by [...] (human T-cell lymphotropic virus type 1), the presence of which can be confirmed in tissue biopsies via in situ hybridization for the specific viral transcript HBZ.
Adult T-cell leukaemia/lymphoma involving skin. In situ hybridization for HBZ, a viral transcript specific for HTLV-1. Positive signals (brown dots) are observed in the neoplastic cells forming a Pautrier microabscess.
A: HTLV-1
Back Extra: Adult T-cell leukaemia/lymphoma
- Clinical: Adult T-cell leukaemia/lymphoma often presents with skin lesions, including patch, plaque, multipapular, nodulotumoural, erythrodermic, and purpuric types.
- Micro: Histologically, the neoplastic cells form Pautrier-like microabscesses and show nuclear pleomorphism and mitotic activity.
- Ancillary: The neoplastic cells are positive for CD3, CD4, CD25, and CCR4, and negative for CD8, CD19, and CD20.
Reference Gallery:
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, patch type. The cutaneous manifestations of the patch/plaque and erythrodermic types share similarities with those of mycosis fungoides and Sézary syndrome, respectively.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, plaque type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, multipapular type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, nodulotumoural type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, erythrodermic type.
Adult T-cell leukaemia/lymphoma. Cutaneous manifestations of adult T-cell leukaemia/lymphoma, purpuric type.
Adult T-cell leukaemia/lymphoma involving skin. The epidermis and dermis show infiltration by atypical lymphoid cells with irregularly folded nuclei.
Adult T-cell leukaemia/lymphoma involving skin. The atypical lymphoid cells are immunoreactive for CD3.
Adult T-cell leukaemia/lymphoma involving skin. In situ hybridization for HBZ, a viral transcript specific for HTLV-1. Positive signals (brown dots) are observed in the neoplastic cells forming a Pautrier microabscess.
Adult T-cell leukaemia/lymphoma involving skin. The dermis is entirely involved by atypical lymphoid cells.
Adult T-cell leukaemia/lymphoma involving skin. The dermis is entirely involved by atypical lymphoid cells.
Adult T-cell leukaemia/lymphoma involving skin. The epidermis and dermis show infiltration by atypical lymphoid cells with irregularly folded nuclei.

Q: Histologically, Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma features atypical pleomorphic lymphocytes that exhibit marked [...], characterized by pagetoid infiltration of the epidermis and extensive involvement of adnexal structures.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. The atypical pleomorphic lymphocytes infiltrate the epidermis in a pagetoid fashion.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. The atypical lymphocytes exhibit prominent epitheliotropism, with infiltration of hair follicles (folliculotropism), epidermis (epidermotropism), and sweat glands (syringotropism).
A: epitheliotropism
Back Extra: Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma
- Clinical: Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma presents with generalized or localized skin lesions, commonly involving acral sites, and can rapidly progress to widespread disease with ulcerated tumours.
- Micro: The histopathology shows atypical T lymphocytes with marked epidermotropism and adnexotropism, often with epidermal necrosis and a high proliferative index.
- Ancillary: Immunohistochemistry reveals CD3+, CD8+, CD4− phenotype, with expression of cytotoxic markers (TIA1, granzyme B, perforin) and a high Ki-67 proliferation index (>75%).
Reference Gallery:
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. The atypical pleomorphic lymphocytes infiltrate the epidermis in a pagetoid fashion.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. The atypical lymphocytes exhibit prominent epitheliotropism, with infiltration of hair follicles (folliculotropism), epidermis (epidermotropism), and sweat glands (syringotropism).
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, pathogenesis. Overactivation of JAK-2 through gene fusion events is frequently present in primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. In fusion-negative cases, gain-of-function mutations in JAK2, STAT3, and STAT5B and loss of negative regulators of the JAK/STAT pathway, particularly SH2B3, can be observed.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Nodulotumoural lesions with ulceration.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Necrotic and ulcerated lesions.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Diffuse cutaneous eruption with plaques.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Dermal and subcutaneous lymphoid infiltrates.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Expression of CD8 by neoplastic cells in the epidermis and dermis.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. High proliferative activity highlighted by Ki-67.

Q: The neoplastic cells in Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma typically express cytotoxic markers (e.g., TIA1, granzyme B), have a remarkably high Ki-67 index (>75%), and exhibit a characteristic CD3+, CD4−, and [...]+ immunophenotype.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Expression of CD8 by neoplastic cells in the epidermis and dermis.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. High proliferative activity highlighted by Ki-67.
A: CD8
Back Extra: Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma
- Clinical: Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma presents with generalized or localized skin lesions, commonly involving acral sites, and can rapidly progress to widespread disease with ulcerated tumours.
- Micro: The histopathology shows atypical T lymphocytes with marked epidermotropism and adnexotropism, often with epidermal necrosis and a high proliferative index.
- Ancillary: Immunohistochemistry reveals CD3+, CD8+, CD4− phenotype, with expression of cytotoxic markers (TIA1, granzyme B, perforin) and a high Ki-67 proliferation index (>75%).
Reference Gallery:
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. The atypical pleomorphic lymphocytes infiltrate the epidermis in a pagetoid fashion.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. The atypical lymphocytes exhibit prominent epitheliotropism, with infiltration of hair follicles (folliculotropism), epidermis (epidermotropism), and sweat glands (syringotropism).
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, pathogenesis. Overactivation of JAK-2 through gene fusion events is frequently present in primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. In fusion-negative cases, gain-of-function mutations in JAK2, STAT3, and STAT5B and loss of negative regulators of the JAK/STAT pathway, particularly SH2B3, can be observed.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Nodulotumoural lesions with ulceration.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Necrotic and ulcerated lesions.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Diffuse cutaneous eruption with plaques.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Dermal and subcutaneous lymphoid infiltrates.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Expression of CD8 by neoplastic cells in the epidermis and dermis.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. High proliferative activity highlighted by Ki-67.

Q: Clinically, Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma can present with generalized or localized eruptions (often involving acral sites) that rapidly progress into deeply necrotic and [...].
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Nodulotumoural lesions with ulceration.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Necrotic and ulcerated lesions.
A: ulcerated tumors
Back Extra: Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma
- Clinical: Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma presents with generalized or localized skin lesions, commonly involving acral sites, and can rapidly progress to widespread disease with ulcerated tumours.
- Micro: The histopathology shows atypical T lymphocytes with marked epidermotropism and adnexotropism, often with epidermal necrosis and a high proliferative index.
- Ancillary: Immunohistochemistry reveals CD3+, CD8+, CD4− phenotype, with expression of cytotoxic markers (TIA1, granzyme B, perforin) and a high Ki-67 proliferation index (>75%).
Reference Gallery:
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. The atypical pleomorphic lymphocytes infiltrate the epidermis in a pagetoid fashion.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. The atypical lymphocytes exhibit prominent epitheliotropism, with infiltration of hair follicles (folliculotropism), epidermis (epidermotropism), and sweat glands (syringotropism).
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, pathogenesis. Overactivation of JAK-2 through gene fusion events is frequently present in primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. In fusion-negative cases, gain-of-function mutations in JAK2, STAT3, and STAT5B and loss of negative regulators of the JAK/STAT pathway, particularly SH2B3, can be observed.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Nodulotumoural lesions with ulceration.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Necrotic and ulcerated lesions.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Diffuse cutaneous eruption with plaques.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Dermal and subcutaneous lymphoid infiltrates.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. Expression of CD8 by neoplastic cells in the epidermis and dermis.
Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. High proliferative activity highlighted by Ki-67.

Q: A poorly circumscribed dermal histiocytic proliferation showing sheets of cells with fine vacuoles and strong cytoplasmic positivity for ALK (often due to an underlying ALK translocation) is diagnostic of [...].
ALK-positive histiocytosis involving skin. The histiocytes show cytoplasmic staining for ALK.
ALK-positive histiocytosis involving skin. At this low-power magnification, a poorly circumscribed dermal cell infiltrate is observed (H&E), which was confirmed to consist of ALK-positive histiocytes.
A: ALK-positive histiocytosis
Back Extra: ALK-positive histiocytosis
- Clinical: ALK-positive histiocytosis can present as solitary or multiple nodules or papules, and is more common in females. It can be a single-system or multisystem disease, with the multisystem form often occurring in infancy.
- Micro: The skin shows a non-circumscribed, non-epidermotropic infiltrate comprising sheets of histiocytes. These cells may be large, multinucleated, or spindle-shaped, and often show fine vacuoles and haemosiderin deposition.
- Ancillary: Histiocytes in ALK-positive histiocytosis are ALK-positive and show variable positivity for histiocytic markers like CD68, CD163, and CD14. The Ki-67 proliferation index is low, and ALK translocation is a key diagnostic feature.
Reference Gallery:
ALK-positive histiocytosis involving skin. The dermis shows an infiltrate of histiocytes, some of which are multinucleated, resembling Touton giant cells.
ALK-positive histiocytosis involving skin. The histiocytes have oval to irregularly folded nuclei, lacking overt pleomorphism. They have lightly eosinophilic cytoplasm with fine vacuoles.
ALK-positive histiocytosis involving skin. The histiocytes show cytoplasmic staining for ALK.
ALK-positive histiocytosis involving skin. At this low-power magnification, a poorly circumscribed dermal cell infiltrate is observed (H&E), which was confirmed to consist of ALK-positive histiocytes.
ALK-positive histiocytosis involving skin. The histiocytes have irregularly folded to grooved nuclei and fine chromatin.

Q: Microscopically, the dermal infiltrate in ALK-positive histiocytosis frequently contains multinucleated histiocytes that closely resemble [...], admixed with mononuclear cells exhibiting finely vacuolated cytoplasm and folded nuclei.
ALK-positive histiocytosis involving skin. The dermis shows an infiltrate of histiocytes, some of which are multinucleated, resembling Touton giant cells.
ALK-positive histiocytosis involving skin. The histiocytes have oval to irregularly folded nuclei, lacking overt pleomorphism. They have lightly eosinophilic cytoplasm with fine vacuoles.
ALK-positive histiocytosis involving skin. The histiocytes have irregularly folded to grooved nuclei and fine chromatin.
A: Touton giant cells
Back Extra: ALK-positive histiocytosis
- Clinical: ALK-positive histiocytosis can present as solitary or multiple nodules or papules, and is more common in females. It can be a single-system or multisystem disease, with the multisystem form often occurring in infancy.
- Micro: The skin shows a non-circumscribed, non-epidermotropic infiltrate comprising sheets of histiocytes. These cells may be large, multinucleated, or spindle-shaped, and often show fine vacuoles and haemosiderin deposition.
- Ancillary: Histiocytes in ALK-positive histiocytosis are ALK-positive and show variable positivity for histiocytic markers like CD68, CD163, and CD14. The Ki-67 proliferation index is low, and ALK translocation is a key diagnostic feature.
Reference Gallery:
ALK-positive histiocytosis involving skin. The dermis shows an infiltrate of histiocytes, some of which are multinucleated, resembling Touton giant cells.
ALK-positive histiocytosis involving skin. The histiocytes have oval to irregularly folded nuclei, lacking overt pleomorphism. They have lightly eosinophilic cytoplasm with fine vacuoles.
ALK-positive histiocytosis involving skin. The histiocytes show cytoplasmic staining for ALK.
ALK-positive histiocytosis involving skin. At this low-power magnification, a poorly circumscribed dermal cell infiltrate is observed (H&E), which was confirmed to consist of ALK-positive histiocytes.
ALK-positive histiocytosis involving skin. The histiocytes have irregularly folded to grooved nuclei and fine chromatin.

Q: Histologically, Anaplastic Large Cell Lymphoma often displays a diffuse, infiltrative growth pattern composed of large cells with abundant cytoplasm and characteristic horseshoe-shaped nuclei, which are termed [...].
Systemic ALK-positive anaplastic large cell lymphoma involving skin. A dense lymphoid infiltrate involving the superficial and deep dermis with a wedge-shaped pattern is seen. The infiltrate extends into the subcutaneous fat.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. An infiltration of atypical lymphocytes in the epidermis is observed.
A: hallmark cells
Back Extra: Anaplastic Large Cell Lymphoma
- Clinical: The skin lesions of Anaplastic Large Cell Lymphoma (ALCL) often present as generalized papules, nodules, or ulcerating tumours, which may be present at diagnosis or develop during disease progression.
- Micro: The tumour cells in ALCL show a diffuse, infiltrative growth pattern with characteristic hallmark cells that have abundant cytoplasm, large horseshoe-shaped nuclei, and multiple nucleoli.
- Ancillary: ALK-positive ALCL can be confirmed by immunohistochemistry showing the expression of the ALK fusion protein. Clonal T-cell populations can be identified by TR gene rearrangement studies.
Reference Gallery:
Systemic ALK-positive anaplastic large cell lymphoma involving skin. A dense lymphoid infiltrate involving the superficial and deep dermis with a wedge-shaped pattern is seen. The infiltrate extends into the subcutaneous fat.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. An infiltration of atypical lymphocytes in the epidermis is observed.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. Atypical lymphocytes within the epidermis and dermis are highlighted by CD30.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. The atypical lymphocytes within the epidermis and dermis express the cytotoxic protein perforin.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. There is a perivascular distribution of neoplastic lymphoid cells, which show a nuclear and cytoplasmic expression of ALK, consistent with the presence of an NPM1::ALK fusion gene.

Q: On immunohistochemistry, the large atypical lymphocytes in Anaplastic Large Cell Lymphoma characteristically exhibit strong positivity for [...].
Systemic ALK-positive anaplastic large cell lymphoma involving skin. Atypical lymphocytes within the epidermis and dermis are highlighted by CD30.
A: CD30
Back Extra: Anaplastic Large Cell Lymphoma
- Clinical: The skin lesions of Anaplastic Large Cell Lymphoma (ALCL) often present as generalized papules, nodules, or ulcerating tumours, which may be present at diagnosis or develop during disease progression.
- Micro: The tumour cells in ALCL show a diffuse, infiltrative growth pattern with characteristic hallmark cells that have abundant cytoplasm, large horseshoe-shaped nuclei, and multiple nucleoli.
- Ancillary: ALK-positive ALCL can be confirmed by immunohistochemistry showing the expression of the ALK fusion protein. Clonal T-cell populations can be identified by TR gene rearrangement studies.
Reference Gallery:
Systemic ALK-positive anaplastic large cell lymphoma involving skin. A dense lymphoid infiltrate involving the superficial and deep dermis with a wedge-shaped pattern is seen. The infiltrate extends into the subcutaneous fat.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. An infiltration of atypical lymphocytes in the epidermis is observed.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. Atypical lymphocytes within the epidermis and dermis are highlighted by CD30.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. The atypical lymphocytes within the epidermis and dermis express the cytotoxic protein perforin.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. There is a perivascular distribution of neoplastic lymphoid cells, which show a nuclear and cytoplasmic expression of ALK, consistent with the presence of an NPM1::ALK fusion gene.

Q: A subset of Anaplastic Large Cell Lymphoma is driven by an NPM1::ALK gene fusion, which results in concurrent nuclear and cytoplasmic immunohistochemical staining for [...].
Systemic ALK-positive anaplastic large cell lymphoma involving skin. There is a perivascular distribution of neoplastic lymphoid cells, which show a nuclear and cytoplasmic expression of ALK, consistent with the presence of an NPM1::ALK fusion gene.
A: ALK
Back Extra: Anaplastic Large Cell Lymphoma
- Clinical: The skin lesions of Anaplastic Large Cell Lymphoma (ALCL) often present as generalized papules, nodules, or ulcerating tumours, which may be present at diagnosis or develop during disease progression.
- Micro: The tumour cells in ALCL show a diffuse, infiltrative growth pattern with characteristic hallmark cells that have abundant cytoplasm, large horseshoe-shaped nuclei, and multiple nucleoli.
- Ancillary: ALK-positive ALCL can be confirmed by immunohistochemistry showing the expression of the ALK fusion protein. Clonal T-cell populations can be identified by TR gene rearrangement studies.
Reference Gallery:
Systemic ALK-positive anaplastic large cell lymphoma involving skin. A dense lymphoid infiltrate involving the superficial and deep dermis with a wedge-shaped pattern is seen. The infiltrate extends into the subcutaneous fat.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. An infiltration of atypical lymphocytes in the epidermis is observed.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. Atypical lymphocytes within the epidermis and dermis are highlighted by CD30.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. The atypical lymphocytes within the epidermis and dermis express the cytotoxic protein perforin.
Systemic ALK-positive anaplastic large cell lymphoma involving skin. There is a perivascular distribution of neoplastic lymphoid cells, which show a nuclear and cytoplasmic expression of ALK, consistent with the presence of an NPM1::ALK fusion gene.

Q: In cutaneous involvement of Nodal T follicular helper cell lymphoma, angioimmunoblastic type, the neoplastic T cells typically show strong immunohistochemical positivity for the follicular helper T-cell marker [...], which highlights the atypical perivascular infiltrate.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy. There are medium-sized atypical cells admixed with reactive small lymphocytes and histiocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy. PD1 stain showing strong PD1 expression by the neoplastic T cells.
A: PD1
Back Extra: Nodal T follicular helper cell lymphoma, angioimmunoblastic type
- Clinical: Patients with nodal T follicular helper cell lymphoma, angioimmunoblastic type often present with advanced disease, B symptoms, and cutaneous manifestations such as pruritic erythematous maculopapular rash.
- Micro: The perivascular and/or periadnexal dermal infiltrate is composed of small to medium-sized mildly atypical neoplastic T cells, admixed with reactive lymphocytes, plasma cells, and histiocytes.
- Ancillary: Detection of identical clonal T-cell receptor gene rearrangement in skin biopsy and diagnostic lymph node biopsy confirms skin involvement, and PD1 immunostain helps identify the neoplastic T cells.
Reference Gallery:
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy. There are medium-sized atypical cells admixed with reactive small lymphocytes and histiocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy. PD1 stain showing strong PD1 expression by the neoplastic T cells.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. Light chain immunostains highlight the kappa light chain–restricted plasma cell population.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. Light chain immunostains highlight the kappa restricted plasma cell population. Lambda light chain immunostain.
Nodal T-cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. PD1 immunostain unmasks the PD1-positive neoplastic T cells.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. High-power view of mature plasma cells.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Low-power view of punch biopsy.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Dense nodular infiltrate involving dermis and subcutis, comprising large atypical lymphoid cells in a background of small to medium-sized lymphocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Nodular sheets/clusters and some dispersed large atypical lymphoid cells in a background of small to medium lymphocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). PD1-positive T cells with strong expression more specific for neoplastic T follicular helper cells.

Q: Skin biopsies of Nodal T follicular helper cell lymphoma, angioimmunoblastic type may occasionally be obscured by secondary clonal large B-cell proliferations that are characteristically driven by and positive for [...].
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Low-power view of punch biopsy.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Dense nodular infiltrate involving dermis and subcutis, comprising large atypical lymphoid cells in a background of small to medium-sized lymphocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Nodular sheets/clusters and some dispersed large atypical lymphoid cells in a background of small to medium lymphocytes.
A: Epstein-Barr virus (EBV)
Back Extra: Nodal T follicular helper cell lymphoma, angioimmunoblastic type
- Clinical: Patients with nodal T follicular helper cell lymphoma, angioimmunoblastic type often present with advanced disease, B symptoms, and cutaneous manifestations such as pruritic erythematous maculopapular rash.
- Micro: The perivascular and/or periadnexal dermal infiltrate is composed of small to medium-sized mildly atypical neoplastic T cells, admixed with reactive lymphocytes, plasma cells, and histiocytes.
- Ancillary: Detection of identical clonal T-cell receptor gene rearrangement in skin biopsy and diagnostic lymph node biopsy confirms skin involvement, and PD1 immunostain helps identify the neoplastic T cells.
Reference Gallery:
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy. There are medium-sized atypical cells admixed with reactive small lymphocytes and histiocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy. PD1 stain showing strong PD1 expression by the neoplastic T cells.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. Light chain immunostains highlight the kappa light chain–restricted plasma cell population.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. Light chain immunostains highlight the kappa restricted plasma cell population. Lambda light chain immunostain.
Nodal T-cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. PD1 immunostain unmasks the PD1-positive neoplastic T cells.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. High-power view of mature plasma cells.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Low-power view of punch biopsy.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Dense nodular infiltrate involving dermis and subcutis, comprising large atypical lymphoid cells in a background of small to medium-sized lymphocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Nodular sheets/clusters and some dispersed large atypical lymphoid cells in a background of small to medium lymphocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). PD1-positive T cells with strong expression more specific for neoplastic T follicular helper cells.

Q: To firmly establish skin involvement by Nodal T follicular helper cell lymphoma, angioimmunoblastic type, molecular testing typically demonstrates identical clonal [...] gene rearrangements between the cutaneous infiltrate and the diagnostic lymph node biopsy.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy.
A: T-cell receptor (TCR)
Back Extra: Nodal T follicular helper cell lymphoma, angioimmunoblastic type
- Clinical: Patients with nodal T follicular helper cell lymphoma, angioimmunoblastic type often present with advanced disease, B symptoms, and cutaneous manifestations such as pruritic erythematous maculopapular rash.
- Micro: The perivascular and/or periadnexal dermal infiltrate is composed of small to medium-sized mildly atypical neoplastic T cells, admixed with reactive lymphocytes, plasma cells, and histiocytes.
- Ancillary: Detection of identical clonal T-cell receptor gene rearrangement in skin biopsy and diagnostic lymph node biopsy confirms skin involvement, and PD1 immunostain helps identify the neoplastic T cells.
Reference Gallery:
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy. There are medium-sized atypical cells admixed with reactive small lymphocytes and histiocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type. Perivascular pattern of dermal involvement in a case where identical clonal T-cell receptor gene rearrangement was detected in skin biopsy and diagnostic lymph node biopsy. PD1 stain showing strong PD1 expression by the neoplastic T cells.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. Light chain immunostains highlight the kappa light chain–restricted plasma cell population.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. Light chain immunostains highlight the kappa restricted plasma cell population. Lambda light chain immunostain.
Nodal T-cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. PD1 immunostain unmasks the PD1-positive neoplastic T cells.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with secondary clonal plasma cell proliferation. The T-cell lymphoma is obscured by a dermal monotypic plasmacytic proliferation mimicking primary cutaneous marginal zone lymphoma. High-power view of mature plasma cells.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Low-power view of punch biopsy.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Dense nodular infiltrate involving dermis and subcutis, comprising large atypical lymphoid cells in a background of small to medium-sized lymphocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). Nodular sheets/clusters and some dispersed large atypical lymphoid cells in a background of small to medium lymphocytes.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type, with clonal EBV-positive large B-cell proliferation (secondary EBV-positive diffuse large B-cell lymphoma). PD1-positive T cells with strong expression more specific for neoplastic T follicular helper cells.

Q: Histologic examination of B-lymphoblastic leukaemia/lymphoma shows a dense dermal infiltrate of blastic cells with numerous tingible-body macrophages, often imparting a characteristic [...] pattern.
B-lymphoblastic leukaemia/lymphoma. Skin showing extensive involvement by an infiltrate of immature neoplastic cells involving the full thickness of the dermis with sparing of the epidermis.
B-lymphoblastic leukaemia/lymphoma. The neoplastic cells have blastoid features, with open chromatin and variably prominent nucleoli. Mitotic figures are identified readily. Numerous tingible-body macrophages are present, imparting a starry-sky pattern.
A: starry-sky
Back Extra: B-lymphoblastic leukaemia/lymphoma
- Clinical: B-lymphoblastic leukaemia/lymphoma typically presents with solitary or multiple rapidly growing, firm, erythematous to violaceous nodules, often in children and adolescents.
- Micro: Skin biopsy shows a dense, monotonous dermal infiltrate with sheets of neoplastic cells, sparing the upper dermis and surrounding appendages, and dissecting collagen fibres of small to medium-sized blastic cells.
- Ancillary: Immunohistochemistry is positive for CD19, CD79a, CD22, TdT, CD34, CD10, CD24, and PAX5, while CD20 is typically negative.
Reference Gallery:
B-lymphoblastic leukaemia/lymphoma. Skin showing extensive involvement by an infiltrate of immature neoplastic cells involving the full thickness of the dermis with sparing of the epidermis.
B-lymphoblastic leukaemia/lymphoma. The neoplastic cells have blastoid features, with open chromatin and variably prominent nucleoli. Mitotic figures are identified readily. Numerous tingible-body macrophages are present, imparting a starry-sky pattern.
B-lymphoblastic leukaemia/lymphoma. The neoplastic cells are positive for CD19.
B-lymphoblastic leukaemia/lymphoma. The neoplastic cells are positive for TdT.

Q: The neoplastic cells of B-lymphoblastic leukaemia/lymphoma characteristically express B-cell markers (e.g., CD19, PAX5) along with the immature lymphoid marker [...].
B-lymphoblastic leukaemia/lymphoma. The neoplastic cells are positive for CD19.
B-lymphoblastic leukaemia/lymphoma. The neoplastic cells are positive for TdT.
A: TdT
Back Extra: B-lymphoblastic leukaemia/lymphoma
- Clinical: B-lymphoblastic leukaemia/lymphoma typically presents with solitary or multiple rapidly growing, firm, erythematous to violaceous nodules, often in children and adolescents.
- Micro: Skin biopsy shows a dense, monotonous dermal infiltrate with sheets of neoplastic cells, sparing the upper dermis and surrounding appendages, and dissecting collagen fibres of small to medium-sized blastic cells.
- Ancillary: Immunohistochemistry is positive for CD19, CD79a, CD22, TdT, CD34, CD10, CD24, and PAX5, while CD20 is typically negative.
Reference Gallery:
B-lymphoblastic leukaemia/lymphoma. Skin showing extensive involvement by an infiltrate of immature neoplastic cells involving the full thickness of the dermis with sparing of the epidermis.
B-lymphoblastic leukaemia/lymphoma. The neoplastic cells have blastoid features, with open chromatin and variably prominent nucleoli. Mitotic figures are identified readily. Numerous tingible-body macrophages are present, imparting a starry-sky pattern.
B-lymphoblastic leukaemia/lymphoma. The neoplastic cells are positive for CD19.
B-lymphoblastic leukaemia/lymphoma. The neoplastic cells are positive for TdT.

Q: Clinically, patients with Blastic Plasmacytoid Dendritic Cell Neoplasm characteristically present with cutaneous lesions that are often described as violaceous or [...] (bruise-like) in appearance.
Blastic plasmacytoid dendritic cell neoplasm. Clinical presentation with macular or slightly infiltrated contusiform lesions.
A: contusiform
Back Extra: Blastic Plasmacytoid Dendritic Cell Neoplasm
- Clinical: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) typically presents with skin lesions that are violaceous, contusiform, or brown, and may involve the upper thorax, head, and neck.
- Micro: The neoplastic infiltrate of BPDCN is characterized by a diffuse monotonous infiltrate of medium-sized immature blastic cells with scant cytoplasm and eccentric nuclei.
- Ancillary: BPDCN cells are uniformly positive for CD4, CD56, and CD123, and show strong expression of TCF4 and absence of lineage-specific markers.
Reference Gallery:
Blastic plasmacytoid dendritic cell neoplasm. Non-epidermotropic confluent infiltrate of tumour cells in all dermal layers.
Blastic plasmacytoid dendritic cell neoplasm. Dense infiltrate of blasts with nuclear pleomorphism and mitoses.
Blastic plasmacytoid dendritic cell neoplasm. Intratumoural erythrocyte extravasation.
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD4 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD56 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD123 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Ki-67 proliferative activity index (~10–15%) of tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm involving skin. The dermis shows an extensive diffuse infiltrate of neoplastic cells.
Blastic plasmacytoid dendritic cell neoplasm involving skin. The neoplastic cells are immunoreactive for CD56.
Blastic plasmacytoid dendritic cell neoplasm. Clinical presentation with macular or slightly infiltrated contusiform lesions.

Q: Microscopically, Blastic Plasmacytoid Dendritic Cell Neoplasm typically shows a dense, non-epidermotropic dermal infiltrate composed of monotonous, immature [...] cells with scant cytoplasm and eccentric nuclei.
Blastic plasmacytoid dendritic cell neoplasm. Non-epidermotropic confluent infiltrate of tumour cells in all dermal layers.
Blastic plasmacytoid dendritic cell neoplasm. Dense infiltrate of blasts with nuclear pleomorphism and mitoses.
A: blastic
Back Extra: Blastic Plasmacytoid Dendritic Cell Neoplasm
- Clinical: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) typically presents with skin lesions that are violaceous, contusiform, or brown, and may involve the upper thorax, head, and neck.
- Micro: The neoplastic infiltrate of BPDCN is characterized by a diffuse monotonous infiltrate of medium-sized immature blastic cells with scant cytoplasm and eccentric nuclei.
- Ancillary: BPDCN cells are uniformly positive for CD4, CD56, and CD123, and show strong expression of TCF4 and absence of lineage-specific markers.
Reference Gallery:
Blastic plasmacytoid dendritic cell neoplasm. Non-epidermotropic confluent infiltrate of tumour cells in all dermal layers.
Blastic plasmacytoid dendritic cell neoplasm. Dense infiltrate of blasts with nuclear pleomorphism and mitoses.
Blastic plasmacytoid dendritic cell neoplasm. Intratumoural erythrocyte extravasation.
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD4 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD56 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD123 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Ki-67 proliferative activity index (~10–15%) of tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm involving skin. The dermis shows an extensive diffuse infiltrate of neoplastic cells.
Blastic plasmacytoid dendritic cell neoplasm involving skin. The neoplastic cells are immunoreactive for CD56.
Blastic plasmacytoid dendritic cell neoplasm. Clinical presentation with macular or slightly infiltrated contusiform lesions.

Q: The neoplastic cells in Blastic Plasmacytoid Dendritic Cell Neoplasm exhibit a highly characteristic immunohistochemical profile with strong, uniform co-expression of CD4, CD56, and [...].
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD4 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD56 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD123 by all tumour cells (immunohistochemistry, APAAP).
A: CD123
Back Extra: Blastic Plasmacytoid Dendritic Cell Neoplasm
- Clinical: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) typically presents with skin lesions that are violaceous, contusiform, or brown, and may involve the upper thorax, head, and neck.
- Micro: The neoplastic infiltrate of BPDCN is characterized by a diffuse monotonous infiltrate of medium-sized immature blastic cells with scant cytoplasm and eccentric nuclei.
- Ancillary: BPDCN cells are uniformly positive for CD4, CD56, and CD123, and show strong expression of TCF4 and absence of lineage-specific markers.
Reference Gallery:
Blastic plasmacytoid dendritic cell neoplasm. Non-epidermotropic confluent infiltrate of tumour cells in all dermal layers.
Blastic plasmacytoid dendritic cell neoplasm. Dense infiltrate of blasts with nuclear pleomorphism and mitoses.
Blastic plasmacytoid dendritic cell neoplasm. Intratumoural erythrocyte extravasation.
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD4 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD56 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Expression of CD123 by all tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm. Ki-67 proliferative activity index (~10–15%) of tumour cells (immunohistochemistry, APAAP).
Blastic plasmacytoid dendritic cell neoplasm involving skin. The dermis shows an extensive diffuse infiltrate of neoplastic cells.
Blastic plasmacytoid dendritic cell neoplasm involving skin. The neoplastic cells are immunoreactive for CD56.
Blastic plasmacytoid dendritic cell neoplasm. Clinical presentation with macular or slightly infiltrated contusiform lesions.

Q: Skin lesions in an elderly male demonstrating a nodular dermal infiltrate of medium-sized cells with eccentric nuclei and clumped chromatin, often with scattered apoptotic cells, are highly characteristic of [...].
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Mature plasmacytoid dendritic cell proliferation associated with acute myeloid leukaemia. Pandermal infiltrates and nodular infiltrates of plasmacytoid dendritic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Aggregates of plasmacytoid dendritic cells with irregular nuclear contour. Note the presence of apoptotic cells.
A: Mature Plasmacytoid Dendritic Cell Proliferation Associated with Myeloid Neoplasm
Back Extra: Mature Plasmacytoid Dendritic Cell Proliferation Associated with Myeloid Neoplasm
- Clinical: Mature Plasmacytoid Dendritic Cell Proliferation (MPDCP) associated with myeloid neoplasms often manifests as rash, macules, and papules, primarily in males around 69–72 years of age.
- Micro: MPDCP is characterized by medium-sized cells with eccentrically located nuclei and clumped chromatin, forming a dermal infiltrate with a nodular pattern.
- Ancillary: MPDCP shows a specific immunophenotype, including positivity for CD123 and CD4, and a low Ki-67 proliferation index.
Reference Gallery:
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Mature plasmacytoid dendritic cell proliferation associated with acute myeloid leukaemia. Pandermal infiltrates and nodular infiltrates of plasmacytoid dendritic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Aggregates of plasmacytoid dendritic cells with irregular nuclear contour. Note the presence of apoptotic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Expression of CD123 by the plasmacytoid dendritic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Expression of CD3 by admixed T cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Ki-67 immunohistochemistry showing a low proliferative activity of the plasmacytoid dendritic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Expression of CD2-associated protein (CD2AP) by plasmacytoid dendritic cells.
Clonal plasmacytoid dendritic cell proliferations. Proposed scheme outlining the relationships between mature plasmacytoid dendritic cell proliferations, associated with myeloid neoplasms, and blastic plasmacytoid dendritic cell neoplasm. BPDCN, blastic plasmacytoid dendritic cell neoplasm; pDC-AML, acute myeloid leukaemia with plasmacytoid dendritic cell expansion; pDC-CMML, chronic myelomonocytic leukaemia with plasmacytoid dendritic cell expansion; pDCs, plasmacytoid dendritic cells.

Q: In Mature Plasmacytoid Dendritic Cell Proliferation Associated with Myeloid Neoplasm, the neoplastic cells characteristically express CD4 and the highly specific plasmacytoid dendritic cell marker [...], while maintaining a notably low Ki-67 proliferation index.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Expression of CD123 by the plasmacytoid dendritic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Ki-67 immunohistochemistry showing a low proliferative activity of the plasmacytoid dendritic cells.
A: CD123
Back Extra: Mature Plasmacytoid Dendritic Cell Proliferation Associated with Myeloid Neoplasm
- Clinical: Mature Plasmacytoid Dendritic Cell Proliferation (MPDCP) associated with myeloid neoplasms often manifests as rash, macules, and papules, primarily in males around 69–72 years of age.
- Micro: MPDCP is characterized by medium-sized cells with eccentrically located nuclei and clumped chromatin, forming a dermal infiltrate with a nodular pattern.
- Ancillary: MPDCP shows a specific immunophenotype, including positivity for CD123 and CD4, and a low Ki-67 proliferation index.
Reference Gallery:
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Mature plasmacytoid dendritic cell proliferation associated with acute myeloid leukaemia. Pandermal infiltrates and nodular infiltrates of plasmacytoid dendritic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Aggregates of plasmacytoid dendritic cells with irregular nuclear contour. Note the presence of apoptotic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Expression of CD123 by the plasmacytoid dendritic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Expression of CD3 by admixed T cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Ki-67 immunohistochemistry showing a low proliferative activity of the plasmacytoid dendritic cells.
Mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm. Expression of CD2-associated protein (CD2AP) by plasmacytoid dendritic cells.
Clonal plasmacytoid dendritic cell proliferations. Proposed scheme outlining the relationships between mature plasmacytoid dendritic cell proliferations, associated with myeloid neoplasms, and blastic plasmacytoid dendritic cell neoplasm. BPDCN, blastic plasmacytoid dendritic cell neoplasm; pDC-AML, acute myeloid leukaemia with plasmacytoid dendritic cell expansion; pDC-CMML, chronic myelomonocytic leukaemia with plasmacytoid dendritic cell expansion; pDCs, plasmacytoid dendritic cells.

Q: A skin biopsy demonstrating a dense, diffuse infiltrate of monotonous, medium-sized lymphoid cells with frequent mitotic figures that fills the dermis and spares the epidermis is characteristic of cutaneous involvement by [...].
Burkitt lymphoma. The patient was an adult woman from Africa. This skin lesion corresponds to a dense, diffuse lymphoid infiltrate filling most of the dermis and sparing the epidermis.
Burkitt lymphoma. The tumour cells are medium-sized, with round or slightly irregular nuclei, coarsely stippled chromatin, small nucleoli, and a small amount of eosinophilic cytoplasm. Mitotic figures are frequent (oil immersion).
A: Burkitt Lymphoma
Back Extra: Burkitt Lymphoma
- Clinical: Cutaneous involvement of Burkitt lymphoma can present as subcutaneous nodules or macules, often with extracutaneous disease and haematogenous dissemination.
- Micro: A diffuse infiltrate of medium-sized, monotonous lymphoid cells with round nuclei, multiple nucleoli, and deeply basophilic cytoplasm is characteristic.
- Ancillary: The neoplastic cells are positive for CD20, CD10, BCL6, and MYC, with a nearly 100% Ki-67 proliferation index and MYC::IGH translocation.
Reference Gallery:
Burkitt lymphoma. The patient was an adult woman from Africa. This skin lesion corresponds to a dense, diffuse lymphoid infiltrate filling most of the dermis and sparing the epidermis.
Burkitt lymphoma. The tumour cells are medium-sized, with round or slightly irregular nuclei, coarsely stippled chromatin, small nucleoli, and a small amount of eosinophilic cytoplasm. Mitotic figures are frequent (oil immersion).

Q: In Burkitt Lymphoma, the highly aggressive tumor is characterized by an exceptionally high proliferation index (nearly 100% Ki-67), which visually corresponds on H&E to the presence of frequent [...] among the medium-sized, monotonous cells.
Burkitt lymphoma. The tumour cells are medium-sized, with round or slightly irregular nuclei, coarsely stippled chromatin, small nucleoli, and a small amount of eosinophilic cytoplasm. Mitotic figures are frequent (oil immersion).
A: mitotic figures
Back Extra: Burkitt Lymphoma
- Clinical: Cutaneous involvement of Burkitt lymphoma can present as subcutaneous nodules or macules, often with extracutaneous disease and haematogenous dissemination.
- Micro: A diffuse infiltrate of medium-sized, monotonous lymphoid cells with round nuclei, multiple nucleoli, and deeply basophilic cytoplasm is characteristic.
- Ancillary: The neoplastic cells are positive for CD20, CD10, BCL6, and MYC, with a nearly 100% Ki-67 proliferation index and MYC::IGH translocation.
Reference Gallery:
Burkitt lymphoma. The patient was an adult woman from Africa. This skin lesion corresponds to a dense, diffuse lymphoid infiltrate filling most of the dermis and sparing the epidermis.
Burkitt lymphoma. The tumour cells are medium-sized, with round or slightly irregular nuclei, coarsely stippled chromatin, small nucleoli, and a small amount of eosinophilic cytoplasm. Mitotic figures are frequent (oil immersion).

Q: Microscopically, skin involvement by Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma is characterized by a monotonous infiltrate of small lymphocytes with clumped chromatin, which may form small [...] composed of larger prolymphocytes and paraimmunoblasts.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving the skin. The predominant cells in chronic lymphocytic leukaemia / small lymphocytic lymphoma are small lymphocytes with scant cytoplasm and a round nucleus with clumped chromatin. In addition to the monotonous diffuse small cell infiltrate (left), there may be small proliferation centres (right) with clustering of larger cells: prolymphocytes (slightly larger with more dispersed chromatin and small nucleoli) and paraimmunoblasts (large cells with slightly basophilic cytoplasm and round to oval nuclei with dispersed chromatin and central nucleoli).
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Monotonous infiltrate of small lymphocytes in the dermis.
A: proliferation centers
Back Extra: Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma
- Clinical: Chronic lymphocytic leukaemia / small lymphocytic lymphoma (CLL/SLL) usually presents in patients with known CLL, with skin involvement often manifesting as erythematous papules, plaques, nodules, or tumours.
- Micro: CLL/SLL in the skin appears as a perivascular, periadnexal, nodular, diffuse, or band-like infiltrate of small, monotonous lymphocytes with clumped chromatin.
- Ancillary: Diagnosis is supported by immunohistochemical findings, including CD20+, CD5+, and CD23+ expression, and negative for CD10, cyclin D1, and SOX11.
Reference Gallery:
Chronic lymphocytic leukaemia and actinic keratosis. Skin infiltration by a chronic lymphocytic leukaemia at the site of an actinic keratosis.
Chronic lymphocytic leukaemia and actinic keratosis. Close-up view of the lymphoid skin infiltration with monotonous small lymphocytic cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving the skin. The predominant cells in chronic lymphocytic leukaemia / small lymphocytic lymphoma are small lymphocytes with scant cytoplasm and a round nucleus with clumped chromatin. In addition to the monotonous diffuse small cell infiltrate (left), there may be small proliferation centres (right) with clustering of larger cells: prolymphocytes (slightly larger with more dispersed chromatin and small nucleoli) and paraimmunoblasts (large cells with slightly basophilic cytoplasm and round to oval nuclei with dispersed chromatin and central nucleoli).
Chronic lymphocytic leukaemia. Transformation of chronic lymphocytic leukaemia to diffuse large B-cell lymphoma (Richter syndrome) in the skin. A dense diffuse dermal infiltrate of large atypical lymphocytes with prominent nucleoli and frequent mitoses.
Chronic lymphocytic leukaemia. Transformation of chronic lymphocytic leukaemia to diffuse large B-cell lymphoma (Richter syndrome) in the skin. High proliferation index with Ki-67 stain.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma. Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving the skin in association with basal cell carcinoma in a patient with a history of chronic lymphocytic leukaemia / small lymphocytic lymphoma. The infiltrate is CD20+
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Monotonous infiltrate of small lymphocytes in the dermis.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Immunohistochemistry shows a predominance of CD20+ B cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Coexpression of CD23 by the tumour cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. CD3+ T cells are a small minority.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. CD5 shows a biphasic staining pattern: strong expression in scattered reactive T cells and weaker expression in the neoplastic B-cell infiltrate.

Q: The immunohistochemical profile of Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma features a predominance of CD20+ B-cells that characteristically co-express CD5 (weaker than reactive T-cells) and [...] (unlike mantle cell lymphoma).
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Immunohistochemistry shows a predominance of CD20+ B cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Coexpression of CD23 by the tumour cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. CD5 shows a biphasic staining pattern: strong expression in scattered reactive T cells and weaker expression in the neoplastic B-cell infiltrate.
A: CD23
Back Extra: Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma
- Clinical: Chronic lymphocytic leukaemia / small lymphocytic lymphoma (CLL/SLL) usually presents in patients with known CLL, with skin involvement often manifesting as erythematous papules, plaques, nodules, or tumours.
- Micro: CLL/SLL in the skin appears as a perivascular, periadnexal, nodular, diffuse, or band-like infiltrate of small, monotonous lymphocytes with clumped chromatin.
- Ancillary: Diagnosis is supported by immunohistochemical findings, including CD20+, CD5+, and CD23+ expression, and negative for CD10, cyclin D1, and SOX11.
Reference Gallery:
Chronic lymphocytic leukaemia and actinic keratosis. Skin infiltration by a chronic lymphocytic leukaemia at the site of an actinic keratosis.
Chronic lymphocytic leukaemia and actinic keratosis. Close-up view of the lymphoid skin infiltration with monotonous small lymphocytic cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving the skin. The predominant cells in chronic lymphocytic leukaemia / small lymphocytic lymphoma are small lymphocytes with scant cytoplasm and a round nucleus with clumped chromatin. In addition to the monotonous diffuse small cell infiltrate (left), there may be small proliferation centres (right) with clustering of larger cells: prolymphocytes (slightly larger with more dispersed chromatin and small nucleoli) and paraimmunoblasts (large cells with slightly basophilic cytoplasm and round to oval nuclei with dispersed chromatin and central nucleoli).
Chronic lymphocytic leukaemia. Transformation of chronic lymphocytic leukaemia to diffuse large B-cell lymphoma (Richter syndrome) in the skin. A dense diffuse dermal infiltrate of large atypical lymphocytes with prominent nucleoli and frequent mitoses.
Chronic lymphocytic leukaemia. Transformation of chronic lymphocytic leukaemia to diffuse large B-cell lymphoma (Richter syndrome) in the skin. High proliferation index with Ki-67 stain.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma. Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving the skin in association with basal cell carcinoma in a patient with a history of chronic lymphocytic leukaemia / small lymphocytic lymphoma. The infiltrate is CD20+
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Monotonous infiltrate of small lymphocytes in the dermis.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Immunohistochemistry shows a predominance of CD20+ B cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Coexpression of CD23 by the tumour cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. CD3+ T cells are a small minority.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. CD5 shows a biphasic staining pattern: strong expression in scattered reactive T cells and weaker expression in the neoplastic B-cell infiltrate.

Q: When Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma rapidly progresses to form a dense dermal infiltrate of large atypical lymphocytes with prominent nucleoli and a high Ki-67 proliferation index, it indicates Richter syndrome, which is a transformation to [...].
Chronic lymphocytic leukaemia. Transformation of chronic lymphocytic leukaemia to diffuse large B-cell lymphoma (Richter syndrome) in the skin. A dense diffuse dermal infiltrate of large atypical lymphocytes with prominent nucleoli and frequent mitoses.
Chronic lymphocytic leukaemia. Transformation of chronic lymphocytic leukaemia to diffuse large B-cell lymphoma (Richter syndrome) in the skin. High proliferation index with Ki-67 stain.
A: diffuse large B-cell lymphoma
Back Extra: Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma
- Clinical: Chronic lymphocytic leukaemia / small lymphocytic lymphoma (CLL/SLL) usually presents in patients with known CLL, with skin involvement often manifesting as erythematous papules, plaques, nodules, or tumours.
- Micro: CLL/SLL in the skin appears as a perivascular, periadnexal, nodular, diffuse, or band-like infiltrate of small, monotonous lymphocytes with clumped chromatin.
- Ancillary: Diagnosis is supported by immunohistochemical findings, including CD20+, CD5+, and CD23+ expression, and negative for CD10, cyclin D1, and SOX11.
Reference Gallery:
Chronic lymphocytic leukaemia and actinic keratosis. Skin infiltration by a chronic lymphocytic leukaemia at the site of an actinic keratosis.
Chronic lymphocytic leukaemia and actinic keratosis. Close-up view of the lymphoid skin infiltration with monotonous small lymphocytic cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving the skin. The predominant cells in chronic lymphocytic leukaemia / small lymphocytic lymphoma are small lymphocytes with scant cytoplasm and a round nucleus with clumped chromatin. In addition to the monotonous diffuse small cell infiltrate (left), there may be small proliferation centres (right) with clustering of larger cells: prolymphocytes (slightly larger with more dispersed chromatin and small nucleoli) and paraimmunoblasts (large cells with slightly basophilic cytoplasm and round to oval nuclei with dispersed chromatin and central nucleoli).
Chronic lymphocytic leukaemia. Transformation of chronic lymphocytic leukaemia to diffuse large B-cell lymphoma (Richter syndrome) in the skin. A dense diffuse dermal infiltrate of large atypical lymphocytes with prominent nucleoli and frequent mitoses.
Chronic lymphocytic leukaemia. Transformation of chronic lymphocytic leukaemia to diffuse large B-cell lymphoma (Richter syndrome) in the skin. High proliferation index with Ki-67 stain.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma. Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving the skin in association with basal cell carcinoma in a patient with a history of chronic lymphocytic leukaemia / small lymphocytic lymphoma. The infiltrate is CD20+
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Monotonous infiltrate of small lymphocytes in the dermis.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Immunohistochemistry shows a predominance of CD20+ B cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. Coexpression of CD23 by the tumour cells.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. CD3+ T cells are a small minority.
Chronic lymphocytic leukaemia / small lymphocytic lymphoma involving skin. CD5 shows a biphasic staining pattern: strong expression in scattered reactive T cells and weaker expression in the neoplastic B-cell infiltrate.

Q: Patients with [...] often present clinically with generalized scaly patches and plaques, deep dermal or subcutaneous tumors, and prominent ulceration.
Primary cutaneous gamma/delta T-cell lymphoma. Polycyclic dyschromic patches and plaques with scale in early presentation.
Primary cutaneous gamma/delta T-cell lymphoma. Ulcerated tumour.
A: Primary Cutaneous Gamma/Delta T-Cell Lymphoma
Q: Primary Cutaneous Gamma/Delta T-Cell Lymphoma
- Clinical: Patients with [...] often present with generalized scaly patches and plaques, deep dermal and/or subcutaneous nodules or tumours, and ulceration.
- Micro: In [...], the malignant cells are predominantly medium-sized with elongated nuclei and coarse chromatin, and may involve any skin compartment.
- Ancillary: [...] shows a typical immunophenotype of CD3+, CD2+, CD7+/−, CD5−, and negative for TCRβ, with expression of cytotoxic proteins such as granzyme B and perforin.
Reference Gallery:
Primary cutaneous gamma/delta T-cell lymphoma. Polycyclic dyschromic patches and plaques with scale in early presentation.
Primary cutaneous gamma/delta T-cell lymphoma. Ulcerated tumour.
Primary cutaneous gamma/delta T-cell lymphoma. Ulcerated plaque of primary cutaneous gamma/delta T-cell lymphoma. Diffuse superficial and dermal infiltrate, with sheets of large atypical lymphocytes with cytotoxic tissue damage and large ulcer.
Primary cutaneous gamma/delta T-cell lymphoma. Panniculitic primary cutaneous gamma/delta T-cell lymphoma. Diffuse sheets of medium to large atypical cells infiltrate the fat lobules and rim adipocytes.
Primary cutaneous gamma/delta T-cell lymphoma. Intraepidermal and dermal primary cutaneous gamma/delta T-cell lymphoma. Epidermotropic and superficial dermal pattern with cytotoxic tissue alteration (haemorrhage) and Pautrier-like microabscesses.
Primary cutaneous gamma/delta T-cell lymphoma. Eccrine involvement in primary cutaneous gamma/delta T-cell lymphoma. Deep dermal/panniculitic infiltrates encase and are tropic to the adnexal epithelium.
Primary cutaneous gamma/delta T-cell lymphoma. TCRδ immunohistochemistry. Tumour cells are diffusely positive.
A: Primary Cutaneous Gamma/Delta T-Cell Lymphoma; Primary Cutaneous Gamma/Delta T-Cell Lymphoma; Primary Cutaneous Gamma/Delta T-Cell Lymphoma

Q: Histologically, Primary Cutaneous Gamma/Delta T-Cell Lymphoma can involve any skin compartment and frequently demonstrates a deep [...] pattern where medium-to-large atypical lymphocytes infiltrate fat lobules and rim adipocytes.
Primary cutaneous gamma/delta T-cell lymphoma. Panniculitic primary cutaneous gamma/delta T-cell lymphoma. Diffuse sheets of medium to large atypical cells infiltrate the fat lobules and rim adipocytes.
A: panniculitic
Q: Primary Cutaneous Gamma/Delta T-Cell Lymphoma
- Clinical: Patients with [...] often present with generalized scaly patches and plaques, deep dermal and/or subcutaneous nodules or tumours, and ulceration.
- Micro: In [...], the malignant cells are predominantly medium-sized with elongated nuclei and coarse chromatin, and may involve any skin compartment.
- Ancillary: [...] shows a typical immunophenotype of CD3+, CD2+, CD7+/−, CD5−, and negative for TCRβ, with expression of cytotoxic proteins such as granzyme B and perforin.
Reference Gallery:
Primary cutaneous gamma/delta T-cell lymphoma. Polycyclic dyschromic patches and plaques with scale in early presentation.
Primary cutaneous gamma/delta T-cell lymphoma. Ulcerated tumour.
Primary cutaneous gamma/delta T-cell lymphoma. Ulcerated plaque of primary cutaneous gamma/delta T-cell lymphoma. Diffuse superficial and dermal infiltrate, with sheets of large atypical lymphocytes with cytotoxic tissue damage and large ulcer.
Primary cutaneous gamma/delta T-cell lymphoma. Panniculitic primary cutaneous gamma/delta T-cell lymphoma. Diffuse sheets of medium to large atypical cells infiltrate the fat lobules and rim adipocytes.
Primary cutaneous gamma/delta T-cell lymphoma. Intraepidermal and dermal primary cutaneous gamma/delta T-cell lymphoma. Epidermotropic and superficial dermal pattern with cytotoxic tissue alteration (haemorrhage) and Pautrier-like microabscesses.
Primary cutaneous gamma/delta T-cell lymphoma. Eccrine involvement in primary cutaneous gamma/delta T-cell lymphoma. Deep dermal/panniculitic infiltrates encase and are tropic to the adnexal epithelium.
Primary cutaneous gamma/delta T-cell lymphoma. TCRδ immunohistochemistry. Tumour cells are diffusely positive.
A: Primary Cutaneous Gamma/Delta T-Cell Lymphoma; Primary Cutaneous Gamma/Delta T-Cell Lymphoma; Primary Cutaneous Gamma/Delta T-Cell Lymphoma

Q: The neoplastic cells of Primary Cutaneous Gamma/Delta T-Cell Lymphoma are typically positive for CD3 and cytotoxic proteins, and characteristically show diffuse immunohistochemical expression of [...] (while being negative for TCRβ).
Primary cutaneous gamma/delta T-cell lymphoma. TCRδ immunohistochemistry. Tumour cells are diffusely positive.
A: TCRδ
Q: Primary Cutaneous Gamma/Delta T-Cell Lymphoma
- Clinical: Patients with [...] often present with generalized scaly patches and plaques, deep dermal and/or subcutaneous nodules or tumours, and ulceration.
- Micro: In [...], the malignant cells are predominantly medium-sized with elongated nuclei and coarse chromatin, and may involve any skin compartment.
- Ancillary: [...] shows a typical immunophenotype of CD3+, CD2+, CD7+/−, CD5−, and negative for TCRβ, with expression of cytotoxic proteins such as granzyme B and perforin.
Reference Gallery:
Primary cutaneous gamma/delta T-cell lymphoma. Polycyclic dyschromic patches and plaques with scale in early presentation.
Primary cutaneous gamma/delta T-cell lymphoma. Ulcerated tumour.
Primary cutaneous gamma/delta T-cell lymphoma. Ulcerated plaque of primary cutaneous gamma/delta T-cell lymphoma. Diffuse superficial and dermal infiltrate, with sheets of large atypical lymphocytes with cytotoxic tissue damage and large ulcer.
Primary cutaneous gamma/delta T-cell lymphoma. Panniculitic primary cutaneous gamma/delta T-cell lymphoma. Diffuse sheets of medium to large atypical cells infiltrate the fat lobules and rim adipocytes.
Primary cutaneous gamma/delta T-cell lymphoma. Intraepidermal and dermal primary cutaneous gamma/delta T-cell lymphoma. Epidermotropic and superficial dermal pattern with cytotoxic tissue alteration (haemorrhage) and Pautrier-like microabscesses.
Primary cutaneous gamma/delta T-cell lymphoma. Eccrine involvement in primary cutaneous gamma/delta T-cell lymphoma. Deep dermal/panniculitic infiltrates encase and are tropic to the adnexal epithelium.
Primary cutaneous gamma/delta T-cell lymphoma. TCRδ immunohistochemistry. Tumour cells are diffusely positive.
A: Primary Cutaneous Gamma/Delta T-Cell Lymphoma; Primary Cutaneous Gamma/Delta T-Cell Lymphoma; Primary Cutaneous Gamma/Delta T-Cell Lymphoma

Q: A typical clinical presentation of rapidly growing, red skin tumors on the lower extremities in an elderly female, combined with a diffuse dermal infiltrate of centroblasts and immunoblasts, is highly characteristic of [...].
Primary cutaneous diffuse large B-cell lymphoma, leg type. Sheets of large cells with centroblasts and immunoblasts.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Typical clinical presentation with tumours on a leg.
A: Primary cutaneous diffuse large B-cell lymphoma, leg type
Back Extra: Primary cutaneous diffuse large B-cell lymphoma, leg type
- Clinical: PCLBCL-LT typically presents in elderly patients, more commonly in women, with red or bluish-red, rapidly growing skin tumours, most frequently on the legs.
- Micro: Histologically, PCLBCL-LT shows diffuse monotonous infiltrates of centroblasts and immunoblasts, with frequent mitotic figures and strong expression of BCL2, IRF4 (MUM1), and FOXP1.
- Ancillary: MYD88 mutations (p.L265P) are highly recurrent, and chromosomal translocations involving IGH, MYC, and BCL6 are common.
Reference Gallery:
Primary cutaneous diffuse large B-cell lymphoma, leg type. Diffuse sheet-like infiltration of the dermis and subcutis by a large cell infiltrate. The epidermis is spared. Some nodularity can be seen.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Sheets of large cells with centroblasts and immunoblasts.
Primary cutaneous diffuse large B-cell lymphoma, leg type. The Ki-67 proliferation rate is high.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong cytoplasmic expression of IgM in the tumour cells.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong nuclear expression of IRF4 (MUM1) in the tumour cells is typical.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong BCL6 expression is seen in many cases.
Primary cutaneous diffuse large B-cell lymphoma, leg type. CD10 is usually negative by immunohistochemistry, but very faint expression that is difficult to separate from CD10 background staining in intermingled cutaneous collagen fibres may be present, as seen here.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Typical clinical presentation with tumours on a leg.

Q: In Primary cutaneous diffuse large B-cell lymphoma, leg type, immunohistochemistry characteristically demonstrates strong nuclear expression of the post-germinal center marker [...].
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong nuclear expression of IRF4 (MUM1) in the tumour cells is typical.
A: IRF4 (MUM1)
Back Extra: Primary cutaneous diffuse large B-cell lymphoma, leg type
- Clinical: PCLBCL-LT typically presents in elderly patients, more commonly in women, with red or bluish-red, rapidly growing skin tumours, most frequently on the legs.
- Micro: Histologically, PCLBCL-LT shows diffuse monotonous infiltrates of centroblasts and immunoblasts, with frequent mitotic figures and strong expression of BCL2, IRF4 (MUM1), and FOXP1.
- Ancillary: MYD88 mutations (p.L265P) are highly recurrent, and chromosomal translocations involving IGH, MYC, and BCL6 are common.
Reference Gallery:
Primary cutaneous diffuse large B-cell lymphoma, leg type. Diffuse sheet-like infiltration of the dermis and subcutis by a large cell infiltrate. The epidermis is spared. Some nodularity can be seen.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Sheets of large cells with centroblasts and immunoblasts.
Primary cutaneous diffuse large B-cell lymphoma, leg type. The Ki-67 proliferation rate is high.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong cytoplasmic expression of IgM in the tumour cells.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong nuclear expression of IRF4 (MUM1) in the tumour cells is typical.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong BCL6 expression is seen in many cases.
Primary cutaneous diffuse large B-cell lymphoma, leg type. CD10 is usually negative by immunohistochemistry, but very faint expression that is difficult to separate from CD10 background staining in intermingled cutaneous collagen fibres may be present, as seen here.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Typical clinical presentation with tumours on a leg.

Q: Histologically, Primary cutaneous diffuse large B-cell lymphoma, leg type shows a dense, sheet-like infiltrate of large B-cells in the dermis and subcutis that characteristically spares the overlying [...].
Primary cutaneous diffuse large B-cell lymphoma, leg type. Diffuse sheet-like infiltration of the dermis and subcutis by a large cell infiltrate. The epidermis is spared. Some nodularity can be seen.
A: epidermis
Back Extra: Primary cutaneous diffuse large B-cell lymphoma, leg type
- Clinical: PCLBCL-LT typically presents in elderly patients, more commonly in women, with red or bluish-red, rapidly growing skin tumours, most frequently on the legs.
- Micro: Histologically, PCLBCL-LT shows diffuse monotonous infiltrates of centroblasts and immunoblasts, with frequent mitotic figures and strong expression of BCL2, IRF4 (MUM1), and FOXP1.
- Ancillary: MYD88 mutations (p.L265P) are highly recurrent, and chromosomal translocations involving IGH, MYC, and BCL6 are common.
Reference Gallery:
Primary cutaneous diffuse large B-cell lymphoma, leg type. Diffuse sheet-like infiltration of the dermis and subcutis by a large cell infiltrate. The epidermis is spared. Some nodularity can be seen.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Sheets of large cells with centroblasts and immunoblasts.
Primary cutaneous diffuse large B-cell lymphoma, leg type. The Ki-67 proliferation rate is high.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong cytoplasmic expression of IgM in the tumour cells.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong nuclear expression of IRF4 (MUM1) in the tumour cells is typical.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Strong BCL6 expression is seen in many cases.
Primary cutaneous diffuse large B-cell lymphoma, leg type. CD10 is usually negative by immunohistochemistry, but very faint expression that is difficult to separate from CD10 background staining in intermingled cutaneous collagen fibres may be present, as seen here.
Primary cutaneous diffuse large B-cell lymphoma, leg type. Typical clinical presentation with tumours on a leg.

Q: Histologically, an EBV-Positive Mucocutaneous Ulcer features a polymorphous infiltrate containing atypical large B cells and characteristic [...] cells.
EBV-positive mucocutaneous ulcer. Atypical Hodgkin-like cells are present.
EBV-positive mucocutaneous ulcer. Atypical Hodgkin-like cells are present.
A: Hodgkin/Reed-Sternberg-like
Back Extra: EBV-Positive Mucocutaneous Ulcer
- Clinical: EBV-Positive Mucocutaneous Ulcer typically presents as a well-circumscribed, painful ulcer on mucosal or cutaneous sites, commonly in elderly patients.
- Micro: The lesion is characterized by a polymorphous infiltrate with atypical large B cells and Hodgkin/Reed–Sternberg-like cells, often with necrosis and angioinvasion.
- Ancillary: The atypical cells are EBV-positive, express B-cell markers (PAX5, OCT2, BOB1), and are frequently positive for CD30 and IRF4.
Reference Gallery:
EBV-positive mucocutaneous ulcer. Ulceration on the penis with fibrin.
EBV-positive mucocutaneous ulcer. Clinical lesion on the thigh.
EBV-positive mucocutaneous ulcer. A large ulcer is present on the hard palate.
EBV-positive mucocutaneous ulcer. Prominent angiotropism is present.
EBV-positive mucocutaneous ulcer. In this example, there is angiodestruction.
EBV-positive mucocutaneous ulcer. Atypical mucosal infiltrate with a polymorphous appearance.
EBV-positive mucocutaneous ulcer. The atypical infiltrate contains epithelioid histiocytes and large cells.
EBV-positive mucocutaneous ulcer. Atypical Hodgkin-like cells are present.
EBV-positive mucocutaneous ulcer. Atypical Hodgkin-like cells are present.
EBV-positive mucocutaneous ulcer. The large cells are positive for CD20.
EBV-positive mucocutaneous ulcer. CD30 expression in the Hodgkin-like cells.
EBV-positive mucocutaneous ulcer. EBV expression in the infiltrate.

Q: In addition to a polymorphous infiltrate, microscopic examination of an EBV-Positive Mucocutaneous Ulcer often reveals prominent [...] (and subsequent angiodestruction) by the atypical cells.
EBV-positive mucocutaneous ulcer. Prominent angiotropism is present.
EBV-positive mucocutaneous ulcer. In this example, there is angiodestruction.
A: angiotropism
Back Extra: EBV-Positive Mucocutaneous Ulcer
- Clinical: EBV-Positive Mucocutaneous Ulcer typically presents as a well-circumscribed, painful ulcer on mucosal or cutaneous sites, commonly in elderly patients.
- Micro: The lesion is characterized by a polymorphous infiltrate with atypical large B cells and Hodgkin/Reed–Sternberg-like cells, often with necrosis and angioinvasion.
- Ancillary: The atypical cells are EBV-positive, express B-cell markers (PAX5, OCT2, BOB1), and are frequently positive for CD30 and IRF4.
Reference Gallery:
EBV-positive mucocutaneous ulcer. Ulceration on the penis with fibrin.
EBV-positive mucocutaneous ulcer. Clinical lesion on the thigh.
EBV-positive mucocutaneous ulcer. A large ulcer is present on the hard palate.
EBV-positive mucocutaneous ulcer. Prominent angiotropism is present.
EBV-positive mucocutaneous ulcer. In this example, there is angiodestruction.
EBV-positive mucocutaneous ulcer. Atypical mucosal infiltrate with a polymorphous appearance.
EBV-positive mucocutaneous ulcer. The atypical infiltrate contains epithelioid histiocytes and large cells.
EBV-positive mucocutaneous ulcer. Atypical Hodgkin-like cells are present.
EBV-positive mucocutaneous ulcer. Atypical Hodgkin-like cells are present.
EBV-positive mucocutaneous ulcer. The large cells are positive for CD20.
EBV-positive mucocutaneous ulcer. CD30 expression in the Hodgkin-like cells.
EBV-positive mucocutaneous ulcer. EBV expression in the infiltrate.

Q: Immunohistochemically, the large, atypical cells in an EBV-Positive Mucocutaneous Ulcer express B-cell markers, EBV (via in situ hybridization), and are frequently positive for the activation marker [...].
EBV-positive mucocutaneous ulcer. CD30 expression in the Hodgkin-like cells.
EBV-positive mucocutaneous ulcer. EBV expression in the infiltrate.
A: CD30
Back Extra: EBV-Positive Mucocutaneous Ulcer
- Clinical: EBV-Positive Mucocutaneous Ulcer typically presents as a well-circumscribed, painful ulcer on mucosal or cutaneous sites, commonly in elderly patients.
- Micro: The lesion is characterized by a polymorphous infiltrate with atypical large B cells and Hodgkin/Reed–Sternberg-like cells, often with necrosis and angioinvasion.
- Ancillary: The atypical cells are EBV-positive, express B-cell markers (PAX5, OCT2, BOB1), and are frequently positive for CD30 and IRF4.
Reference Gallery:
EBV-positive mucocutaneous ulcer. Ulceration on the penis with fibrin.
EBV-positive mucocutaneous ulcer. Clinical lesion on the thigh.
EBV-positive mucocutaneous ulcer. A large ulcer is present on the hard palate.
EBV-positive mucocutaneous ulcer. Prominent angiotropism is present.
EBV-positive mucocutaneous ulcer. In this example, there is angiodestruction.
EBV-positive mucocutaneous ulcer. Atypical mucosal infiltrate with a polymorphous appearance.
EBV-positive mucocutaneous ulcer. The atypical infiltrate contains epithelioid histiocytes and large cells.
EBV-positive mucocutaneous ulcer. Atypical Hodgkin-like cells are present.
EBV-positive mucocutaneous ulcer. Atypical Hodgkin-like cells are present.
EBV-positive mucocutaneous ulcer. The large cells are positive for CD20.
EBV-positive mucocutaneous ulcer. CD30 expression in the Hodgkin-like cells.
EBV-positive mucocutaneous ulcer. EBV expression in the infiltrate.

Q: Patients presenting with bilateral symmetrical involvement of the metadiaphysis of long bones and a bone biopsy demonstrating an infiltrate of foamy macrophages and Touton giant cells most likely have [...].
40–60 years; M:F ratio: 3:1. Bone biopsy showing diffuse infiltration of cancellous bone by foamy histiocytes.
A: Erdheim-Chester Disease
Back Extra: Erdheim-Chester Disease
- Clinical: Erdheim-Chester Disease (ECD) typically manifests with bilateral symmetrical involvement of the metadiaphysis of long bones, retroperitoneal fibrosis, and periaortic infiltration.
- Micro: Histopathologically, ECD is characterized by an infiltrate of foamy macrophages, Touton giant cells, lymphocytes, and plasma cells.
- Ancillary: ECD histiocytes are positive for CD163, CD68, and factor XIIIa, and often show strong cytoplasmic positivity for VE1, indicative of BRAF p.V600E mutations.
Reference Gallery:
40–60 years; M:F ratio: 3:1. Yellowish, pseudotumoural xanthelasma associated with Erdheim–Chester disease.
40–60 years; M:F ratio: 3:1. Yellowish, circumferential xanthelasma-like lesion associated with Erdheim–Chester disease.
40–60 years; M:F ratio: 3:1. A single papular lesion on the foot.
40–60 years; M:F ratio: 3:1. Dermal infiltrate made of foamy macrophages.
40–60 years; M:F ratio: 3:1. Bone biopsy showing diffuse infiltration of cancellous bone by foamy histiocytes.
40–60 years; M:F ratio: 3:1. Diffuse positivity for factor XIIIa.

Q: In Erdheim-Chester Disease, the neoplastic histiocytes are positive for macrophage markers (CD68, CD163) and characteristically show diffuse immunohistochemical positivity for [...].
40–60 years; M:F ratio: 3:1. Diffuse positivity for factor XIIIa.
A: factor XIIIa
Back Extra: Erdheim-Chester Disease
- Clinical: Erdheim-Chester Disease (ECD) typically manifests with bilateral symmetrical involvement of the metadiaphysis of long bones, retroperitoneal fibrosis, and periaortic infiltration.
- Micro: Histopathologically, ECD is characterized by an infiltrate of foamy macrophages, Touton giant cells, lymphocytes, and plasma cells.
- Ancillary: ECD histiocytes are positive for CD163, CD68, and factor XIIIa, and often show strong cytoplasmic positivity for VE1, indicative of BRAF p.V600E mutations.
Reference Gallery:
40–60 years; M:F ratio: 3:1. Yellowish, pseudotumoural xanthelasma associated with Erdheim–Chester disease.
40–60 years; M:F ratio: 3:1. Yellowish, circumferential xanthelasma-like lesion associated with Erdheim–Chester disease.
40–60 years; M:F ratio: 3:1. A single papular lesion on the foot.
40–60 years; M:F ratio: 3:1. Dermal infiltrate made of foamy macrophages.
40–60 years; M:F ratio: 3:1. Bone biopsy showing diffuse infiltration of cancellous bone by foamy histiocytes.
40–60 years; M:F ratio: 3:1. Diffuse positivity for factor XIIIa.

Q: Cutaneous manifestations of Erdheim-Chester Disease frequently include yellowish, circumferential pseudotumoral lesions around the eyes known as [...].
40–60 years; M:F ratio: 3:1. Yellowish, pseudotumoural xanthelasma associated with Erdheim–Chester disease.
40–60 years; M:F ratio: 3:1. Yellowish, circumferential xanthelasma-like lesion associated with Erdheim–Chester disease.
A: xanthelasmas
Back Extra: Erdheim-Chester Disease
- Clinical: Erdheim-Chester Disease (ECD) typically manifests with bilateral symmetrical involvement of the metadiaphysis of long bones, retroperitoneal fibrosis, and periaortic infiltration.
- Micro: Histopathologically, ECD is characterized by an infiltrate of foamy macrophages, Touton giant cells, lymphocytes, and plasma cells.
- Ancillary: ECD histiocytes are positive for CD163, CD68, and factor XIIIa, and often show strong cytoplasmic positivity for VE1, indicative of BRAF p.V600E mutations.
Reference Gallery:
40–60 years; M:F ratio: 3:1. Yellowish, pseudotumoural xanthelasma associated with Erdheim–Chester disease.
40–60 years; M:F ratio: 3:1. Yellowish, circumferential xanthelasma-like lesion associated with Erdheim–Chester disease.
40–60 years; M:F ratio: 3:1. A single papular lesion on the foot.
40–60 years; M:F ratio: 3:1. Dermal infiltrate made of foamy macrophages.
40–60 years; M:F ratio: 3:1. Bone biopsy showing diffuse infiltration of cancellous bone by foamy histiocytes.
40–60 years; M:F ratio: 3:1. Diffuse positivity for factor XIIIa.

Q: Microscopic examination of the skin in Extranodal NK/T-cell lymphoma typically reveals an atypical lymphoid infiltrate with prominent necrosis and a characteristic [...] growth pattern.
Primary cutaneous extranodal NK/T-cell lymphoma. The skin shows extensive infiltration of the dermis and subcutis by lymphoma. Angiocentric growth is evident in addition to prominent necrosis.
Primary cutaneous extranodal NK/T-cell lymphoma. The atypical lymphoid cells are medium-sized and often show irregular nuclear foldings.
A: angiocentric
Back Extra: Extranodal NK/T-cell lymphoma
- Clinical: Cutaneous lesions in extranodal NK/T-cell lymphoma can manifest as nodules, cellulitis-like swellings, or erythematous to purpuric patches. Lesions are often ulcerated and commonly found on the lower extremities.
- Micro: The skin in extranodal NK/T-cell lymphoma shows a dermal and subcutaneous lymphoid infiltrate with prominent necrosis and angiocentric growth. The atypical lymphoid cells are medium-sized with irregular nuclear foldings.
- Ancillary: Lymphoma cells are positive for CD3ε, CD56, and cytotoxic markers, and show EBV positivity by EBER in situ hybridization.
Reference Gallery:
Primary cutaneous extranodal NK/T-cell lymphoma. Nodular lesions on leg (which may or may not ulcerate as disease progresses).
Primary cutaneous extranodal NK/T-cell lymphoma. Crusted erythematous patches on the leg.
Primary cutaneous extranodal NK/T-cell lymphoma. Ulcerated nodule.
Primary cutaneous extranodal NK/T-cell lymphoma. Purpuric plaques over thigh. The arrow indicates a healed lesion that had become pigmented.
Primary cutaneous extranodal NK/T-cell lymphoma. Cellulitis-like swelling around the knee.
Primary cutaneous extranodal NK/T-cell lymphoma. Crusted ulcerated plaque on abdomen.
Primary cutaneous extranodal NK/T-cell lymphoma. The skin shows extensive infiltration of the dermis and subcutis by lymphoma. Angiocentric growth is evident in addition to prominent necrosis.
Primary cutaneous extranodal NK/T-cell lymphoma. Positive immunostaining for CD3.
Primary cutaneous extranodal NK/T-cell lymphoma. Positive staining for CD56.
Primary cutaneous extranodal NK/T-cell lymphoma. In situ hybridization for EBV-encoded small RNA (EBER) shows that most tumour cells are positively labelled.
Primary cutaneous extranodal NK/T-cell lymphoma. The skin shows extensive diffuse dermal infiltration by lymphoid cells.
Primary cutaneous extranodal NK/T-cell lymphoma. The atypical lymphoid cells are medium-sized and often show irregular nuclear foldings.

Q: The neoplastic cells in Extranodal NK/T-cell lymphoma characteristically express CD3, CD56, cytotoxic markers, and universally demonstrate evidence of Epstein-Barr virus via [...] in situ hybridization.
Primary cutaneous extranodal NK/T-cell lymphoma. Positive staining for CD56.
Primary cutaneous extranodal NK/T-cell lymphoma. In situ hybridization for EBV-encoded small RNA (EBER) shows that most tumour cells are positively labelled.
A: EBER
Back Extra: Extranodal NK/T-cell lymphoma
- Clinical: Cutaneous lesions in extranodal NK/T-cell lymphoma can manifest as nodules, cellulitis-like swellings, or erythematous to purpuric patches. Lesions are often ulcerated and commonly found on the lower extremities.
- Micro: The skin in extranodal NK/T-cell lymphoma shows a dermal and subcutaneous lymphoid infiltrate with prominent necrosis and angiocentric growth. The atypical lymphoid cells are medium-sized with irregular nuclear foldings.
- Ancillary: Lymphoma cells are positive for CD3ε, CD56, and cytotoxic markers, and show EBV positivity by EBER in situ hybridization.
Reference Gallery:
Primary cutaneous extranodal NK/T-cell lymphoma. Nodular lesions on leg (which may or may not ulcerate as disease progresses).
Primary cutaneous extranodal NK/T-cell lymphoma. Crusted erythematous patches on the leg.
Primary cutaneous extranodal NK/T-cell lymphoma. Ulcerated nodule.
Primary cutaneous extranodal NK/T-cell lymphoma. Purpuric plaques over thigh. The arrow indicates a healed lesion that had become pigmented.
Primary cutaneous extranodal NK/T-cell lymphoma. Cellulitis-like swelling around the knee.
Primary cutaneous extranodal NK/T-cell lymphoma. Crusted ulcerated plaque on abdomen.
Primary cutaneous extranodal NK/T-cell lymphoma. The skin shows extensive infiltration of the dermis and subcutis by lymphoma. Angiocentric growth is evident in addition to prominent necrosis.
Primary cutaneous extranodal NK/T-cell lymphoma. Positive immunostaining for CD3.
Primary cutaneous extranodal NK/T-cell lymphoma. Positive staining for CD56.
Primary cutaneous extranodal NK/T-cell lymphoma. In situ hybridization for EBV-encoded small RNA (EBER) shows that most tumour cells are positively labelled.
Primary cutaneous extranodal NK/T-cell lymphoma. The skin shows extensive diffuse dermal infiltration by lymphoid cells.
Primary cutaneous extranodal NK/T-cell lymphoma. The atypical lymphoid cells are medium-sized and often show irregular nuclear foldings.

Q: A patient presenting with distinct ulcerated nodules, purpuric plaques, or cellulitis-like swellings on the lower extremities, accompanied by a necrotizing, CD56-positive lymphoid infiltrate, is highly characteristic of [...].
Primary cutaneous extranodal NK/T-cell lymphoma. Nodular lesions on leg (which may or may not ulcerate as disease progresses).
Primary cutaneous extranodal NK/T-cell lymphoma. Purpuric plaques over thigh. The arrow indicates a healed lesion that had become pigmented.
Primary cutaneous extranodal NK/T-cell lymphoma. Cellulitis-like swelling around the knee.
A: Extranodal NK/T-cell lymphoma
Back Extra: Extranodal NK/T-cell lymphoma
- Clinical: Cutaneous lesions in extranodal NK/T-cell lymphoma can manifest as nodules, cellulitis-like swellings, or erythematous to purpuric patches. Lesions are often ulcerated and commonly found on the lower extremities.
- Micro: The skin in extranodal NK/T-cell lymphoma shows a dermal and subcutaneous lymphoid infiltrate with prominent necrosis and angiocentric growth. The atypical lymphoid cells are medium-sized with irregular nuclear foldings.
- Ancillary: Lymphoma cells are positive for CD3ε, CD56, and cytotoxic markers, and show EBV positivity by EBER in situ hybridization.
Reference Gallery:
Primary cutaneous extranodal NK/T-cell lymphoma. Nodular lesions on leg (which may or may not ulcerate as disease progresses).
Primary cutaneous extranodal NK/T-cell lymphoma. Crusted erythematous patches on the leg.
Primary cutaneous extranodal NK/T-cell lymphoma. Ulcerated nodule.
Primary cutaneous extranodal NK/T-cell lymphoma. Purpuric plaques over thigh. The arrow indicates a healed lesion that had become pigmented.
Primary cutaneous extranodal NK/T-cell lymphoma. Cellulitis-like swelling around the knee.
Primary cutaneous extranodal NK/T-cell lymphoma. Crusted ulcerated plaque on abdomen.
Primary cutaneous extranodal NK/T-cell lymphoma. The skin shows extensive infiltration of the dermis and subcutis by lymphoma. Angiocentric growth is evident in addition to prominent necrosis.
Primary cutaneous extranodal NK/T-cell lymphoma. Positive immunostaining for CD3.
Primary cutaneous extranodal NK/T-cell lymphoma. Positive staining for CD56.
Primary cutaneous extranodal NK/T-cell lymphoma. In situ hybridization for EBV-encoded small RNA (EBER) shows that most tumour cells are positively labelled.
Primary cutaneous extranodal NK/T-cell lymphoma. The skin shows extensive diffuse dermal infiltration by lymphoid cells.
Primary cutaneous extranodal NK/T-cell lymphoma. The atypical lymphoid cells are medium-sized and often show irregular nuclear foldings.

Q: Histologically, the large, pleomorphic tumor cells of Histiocytic Sarcoma display abundant eosinophilic cytoplasm and are immunohistochemically positive for CD68 and [...].
Cutaneous histiocytic sarcoma. The neoplastic cells are very large, showing moderate nuclear pleomorphism and mitotic activity. They have abundant eosinophilic cytoplasm.
Cutaneous histiocytic sarcoma. The neoplastic cells are immunoreactive for CD163.
A: CD163
Back Extra: Histiocytic Sarcoma
- Clinical: Patients present with plaques, nodules, and tumours at any site on the body. Some cases are associated with prior or metachronous lymphoma and primary mediastinal germ cell tumours.
- Micro: HS shows a diffuse infiltrate of large tumour cells with abundant eosinophilic cytoplasm, often vacuolated, and variable pleomorphism.
- Ancillary: Immunohistochemically, HS cells express multiple histiocytic markers, including CD163 and CD68, but are negative for Langerhans cell, follicular dendritic cell, and myeloid cell markers.
Reference Gallery:
Histiocytic sarcoma. Large tumours on the face.
Histiocytic sarcoma. An erythematous patch with ulcer on the arm.
Histiocytic sarcoma. A solitary tumour with crust and erythema on the arm.
Histiocytic sarcoma. The skin surface is eroded. The skin shows dense infiltration of tumour cells in the dermis and subcutis.
Histiocytic sarcoma. Diffuse infiltrate of large-sized cells with round to oval nuclei and eosinophilic cytoplasm, intermingled with neutrophils.
Cutaneous histiocytic sarcoma. The neoplastic cells are very large, showing moderate nuclear pleomorphism and mitotic activity. They have abundant eosinophilic cytoplasm.
Cutaneous histiocytic sarcoma. The neoplastic cells are immunoreactive for CD163.

Q: Patients with Histiocytic Sarcoma may present with large cutaneous plaques or tumors; notably, some cases occur in association with primary mediastinal germ cell tumors or a prior/metachronous [...].
Histiocytic sarcoma. Large tumours on the face.
Histiocytic sarcoma. An erythematous patch with ulcer on the arm.
A: lymphoma
Back Extra: Histiocytic Sarcoma
- Clinical: Patients present with plaques, nodules, and tumours at any site on the body. Some cases are associated with prior or metachronous lymphoma and primary mediastinal germ cell tumours.
- Micro: HS shows a diffuse infiltrate of large tumour cells with abundant eosinophilic cytoplasm, often vacuolated, and variable pleomorphism.
- Ancillary: Immunohistochemically, HS cells express multiple histiocytic markers, including CD163 and CD68, but are negative for Langerhans cell, follicular dendritic cell, and myeloid cell markers.
Reference Gallery:
Histiocytic sarcoma. Large tumours on the face.
Histiocytic sarcoma. An erythematous patch with ulcer on the arm.
Histiocytic sarcoma. A solitary tumour with crust and erythema on the arm.
Histiocytic sarcoma. The skin surface is eroded. The skin shows dense infiltration of tumour cells in the dermis and subcutis.
Histiocytic sarcoma. Diffuse infiltrate of large-sized cells with round to oval nuclei and eosinophilic cytoplasm, intermingled with neutrophils.
Cutaneous histiocytic sarcoma. The neoplastic cells are very large, showing moderate nuclear pleomorphism and mitotic activity. They have abundant eosinophilic cytoplasm.
Cutaneous histiocytic sarcoma. The neoplastic cells are immunoreactive for CD163.

Q: In Indeterminate Dendritic Cell Tumor, the neoplastic cells morphologically resemble Langerhans cells; however, transmission electron microscopy characteristically reveals an absence of [...].
Indeterminate dendritic cell tumour. By transmission electron microscopy, an indeterminate cell shows numerous mitochondria, lysosomes, and endoplasmic reticulum, but no Birbeck granules.
Indeterminate dendritic cell tumour. The infiltrate within the dermis is diffuse, consisting of monomorphic mononuclear cells resembling Langerhans cells, with irregular grooved nuclei and abundant eosinophilic cytoplasm.
A: Birbeck granules
Back Extra: Indeterminate Dendritic Cell Tumour
- Clinical: Indeterminate Dendritic Cell Tumour (IDCT) typically presents as single, multifocal, or generalized papules, nodules, or tumours, often soft, erythematous to brownish, and may ulcerate.
- Micro: Histologically, IDCT shows a diffuse dermal infiltrate of monomorphic mononuclear cells with kidney-shaped nuclei and abundant eosinophilic cytoplasm, resembling Langerhans cells.
- Ancillary: Tumour cells are positive for S100 and CD1a but negative for CD207 (langerin); mutations in BRAF (p.V600E), KRAS, or KMT2A (MLL) may be present.
Reference Gallery:
Indeterminate dendritic cell tumour. Multiple generalized isochromatic papular cutaneous lesion.
Indeterminate dendritic cell tumour. Multiple firm erythematous papules on the legs.
Indeterminate dendritic cell tumour. Diffuse dermal infiltrate made of rounded medium-sized histiocytes with single nuclei and abundant cytoplasm.
Indeterminate dendritic cell tumour. Positivity of the tumour cells for CD1a.
Indeterminate dendritic cell tumour. Tumour cells are negative for CD207 (langerin).
Indeterminate dendritic cell tumour. The proliferation is made of medium to large sized mononuclear cells with eosinophilic cytoplasm and indented or kidney-shaped nuclei, admixed with few neutrophils and lymphocytes.
Indeterminate dendritic cell tumour. By transmission electron microscopy, an indeterminate cell shows numerous mitochondria, lysosomes, and endoplasmic reticulum, but no Birbeck granules.
Indeterminate dendritic cell tumour. The infiltrate within the dermis is diffuse, consisting of monomorphic mononuclear cells resembling Langerhans cells, with irregular grooved nuclei and abundant eosinophilic cytoplasm.
Indeterminate dendritic cell tumour. Higher-power view.
Indeterminate dendritic cell tumour. Tumour cells are positive for S100.
Indeterminate dendritic cell tumour. Staining for CD1a is positive in the tumour cells.
Indeterminate dendritic cell tumour. Tumour cells are negative for CD207 (langerin).

Q: The immunophenotype of Indeterminate Dendritic Cell Tumor is typically positive for S100 and CD1a, but is characteristically negative for [...].
Indeterminate dendritic cell tumour. Tumour cells are positive for S100.
Indeterminate dendritic cell tumour. Staining for CD1a is positive in the tumour cells.
Indeterminate dendritic cell tumour. Tumour cells are negative for CD207 (langerin).
A: CD207 (langerin)
Back Extra: Indeterminate Dendritic Cell Tumour
- Clinical: Indeterminate Dendritic Cell Tumour (IDCT) typically presents as single, multifocal, or generalized papules, nodules, or tumours, often soft, erythematous to brownish, and may ulcerate.
- Micro: Histologically, IDCT shows a diffuse dermal infiltrate of monomorphic mononuclear cells with kidney-shaped nuclei and abundant eosinophilic cytoplasm, resembling Langerhans cells.
- Ancillary: Tumour cells are positive for S100 and CD1a but negative for CD207 (langerin); mutations in BRAF (p.V600E), KRAS, or KMT2A (MLL) may be present.
Reference Gallery:
Indeterminate dendritic cell tumour. Multiple generalized isochromatic papular cutaneous lesion.
Indeterminate dendritic cell tumour. Multiple firm erythematous papules on the legs.
Indeterminate dendritic cell tumour. Diffuse dermal infiltrate made of rounded medium-sized histiocytes with single nuclei and abundant cytoplasm.
Indeterminate dendritic cell tumour. Positivity of the tumour cells for CD1a.
Indeterminate dendritic cell tumour. Tumour cells are negative for CD207 (langerin).
Indeterminate dendritic cell tumour. The proliferation is made of medium to large sized mononuclear cells with eosinophilic cytoplasm and indented or kidney-shaped nuclei, admixed with few neutrophils and lymphocytes.
Indeterminate dendritic cell tumour. By transmission electron microscopy, an indeterminate cell shows numerous mitochondria, lysosomes, and endoplasmic reticulum, but no Birbeck granules.
Indeterminate dendritic cell tumour. The infiltrate within the dermis is diffuse, consisting of monomorphic mononuclear cells resembling Langerhans cells, with irregular grooved nuclei and abundant eosinophilic cytoplasm.
Indeterminate dendritic cell tumour. Higher-power view.
Indeterminate dendritic cell tumour. Tumour cells are positive for S100.
Indeterminate dendritic cell tumour. Staining for CD1a is positive in the tumour cells.
Indeterminate dendritic cell tumour. Tumour cells are negative for CD207 (langerin).

Q: Histologically, Indeterminate Dendritic Cell Tumor features a diffuse dermal infiltrate of monomorphic mononuclear cells with abundant eosinophilic cytoplasm and characteristic [...] nuclei.
Indeterminate dendritic cell tumour. Diffuse dermal infiltrate made of rounded medium-sized histiocytes with single nuclei and abundant cytoplasm.
Indeterminate dendritic cell tumour. The proliferation is made of medium to large sized mononuclear cells with eosinophilic cytoplasm and indented or kidney-shaped nuclei, admixed with few neutrophils and lymphocytes.
Indeterminate dendritic cell tumour. Higher-power view.
A: kidney-shaped
Back Extra: Indeterminate Dendritic Cell Tumour
- Clinical: Indeterminate Dendritic Cell Tumour (IDCT) typically presents as single, multifocal, or generalized papules, nodules, or tumours, often soft, erythematous to brownish, and may ulcerate.
- Micro: Histologically, IDCT shows a diffuse dermal infiltrate of monomorphic mononuclear cells with kidney-shaped nuclei and abundant eosinophilic cytoplasm, resembling Langerhans cells.
- Ancillary: Tumour cells are positive for S100 and CD1a but negative for CD207 (langerin); mutations in BRAF (p.V600E), KRAS, or KMT2A (MLL) may be present.
Reference Gallery:
Indeterminate dendritic cell tumour. Multiple generalized isochromatic papular cutaneous lesion.
Indeterminate dendritic cell tumour. Multiple firm erythematous papules on the legs.
Indeterminate dendritic cell tumour. Diffuse dermal infiltrate made of rounded medium-sized histiocytes with single nuclei and abundant cytoplasm.
Indeterminate dendritic cell tumour. Positivity of the tumour cells for CD1a.
Indeterminate dendritic cell tumour. Tumour cells are negative for CD207 (langerin).
Indeterminate dendritic cell tumour. The proliferation is made of medium to large sized mononuclear cells with eosinophilic cytoplasm and indented or kidney-shaped nuclei, admixed with few neutrophils and lymphocytes.
Indeterminate dendritic cell tumour. By transmission electron microscopy, an indeterminate cell shows numerous mitochondria, lysosomes, and endoplasmic reticulum, but no Birbeck granules.
Indeterminate dendritic cell tumour. The infiltrate within the dermis is diffuse, consisting of monomorphic mononuclear cells resembling Langerhans cells, with irregular grooved nuclei and abundant eosinophilic cytoplasm.
Indeterminate dendritic cell tumour. Higher-power view.
Indeterminate dendritic cell tumour. Tumour cells are positive for S100.
Indeterminate dendritic cell tumour. Staining for CD1a is positive in the tumour cells.
Indeterminate dendritic cell tumour. Tumour cells are negative for CD207 (langerin).

Q: Histologically, Intravascular Large B-Cell Lymphoma is characterized by large, atypical tumor cells with vesicular nuclei that are strikingly confined to the lumina of [...].
Intravascular large B-cell lymphoma. High-power magnification shows large tumour cells with vesicular chromatin and several small nucleoli filling vascular spaces.
Intravascular large B-cell lymphoma. Intravascular large B-cell lymphoma involving a cutaneous haemangioma, showing capillaries distended by tumour cells.
A: small blood vessels
Back Extra: Intravascular Large B-Cell Lymphoma
- Clinical: Patients often present with fever of unknown origin, pain, and local organ-specific symptoms. The skin is the most commonly affected organ, with diverse dermatological manifestations such as 'peau d’orange'-like lesions and palpable blue-red discolouration.
- Micro: Histopathology shows large lymphoid cells with vesicular nuclei and multiple prominent nucleoli within the lumina of small vessels, often showing mitotic figures. The growth pattern can be free-floating, cohesive, or marginating/adherent.
- Ancillary: Immunophenotype is characterized by CD20 and CD79a positivity. MYD88 and CD79B mutations are common, and IRF4 (MUM1) is positive in 75-80% of cases.
Reference Gallery:
Intravascular large B-cell lymphoma. An example involving a cutaneous haemangioma.
Intravascular large B-cell lymphoma. An example involving a cutaneous haemangioma, highlighted by CD20 immunohistochemistry. Note confinement of tumour cells to vascular spaces in intravascular large B-cell lymphoma.
Intravascular large B-cell lymphoma. High-power magnification shows large tumour cells with vesicular chromatin and several small nucleoli filling vascular spaces.
Intravascular large B-cell lymphoma. Intravascular large B-cell lymphoma involving a cutaneous haemangioma, showing capillaries distended by tumour cells.
Intravascular large B-cell lymphoma. CD20 immunohistochemistry highlights confinement of tumour cells to vascular spaces in intravascular large B-cell lymphoma involving a cutaneous haemangioma.

Q: In Intravascular Large B-Cell Lymphoma, strong positivity for the B-cell immunohistochemical marker [...] vividly highlights the strict confinement of the malignant tumor cells to the vascular spaces.
Intravascular large B-cell lymphoma. An example involving a cutaneous haemangioma, highlighted by CD20 immunohistochemistry. Note confinement of tumour cells to vascular spaces in intravascular large B-cell lymphoma.
Intravascular large B-cell lymphoma. CD20 immunohistochemistry highlights confinement of tumour cells to vascular spaces in intravascular large B-cell lymphoma involving a cutaneous haemangioma.
A: CD20
Back Extra: Intravascular Large B-Cell Lymphoma
- Clinical: Patients often present with fever of unknown origin, pain, and local organ-specific symptoms. The skin is the most commonly affected organ, with diverse dermatological manifestations such as 'peau d’orange'-like lesions and palpable blue-red discolouration.
- Micro: Histopathology shows large lymphoid cells with vesicular nuclei and multiple prominent nucleoli within the lumina of small vessels, often showing mitotic figures. The growth pattern can be free-floating, cohesive, or marginating/adherent.
- Ancillary: Immunophenotype is characterized by CD20 and CD79a positivity. MYD88 and CD79B mutations are common, and IRF4 (MUM1) is positive in 75-80% of cases.
Reference Gallery:
Intravascular large B-cell lymphoma. An example involving a cutaneous haemangioma.
Intravascular large B-cell lymphoma. An example involving a cutaneous haemangioma, highlighted by CD20 immunohistochemistry. Note confinement of tumour cells to vascular spaces in intravascular large B-cell lymphoma.
Intravascular large B-cell lymphoma. High-power magnification shows large tumour cells with vesicular chromatin and several small nucleoli filling vascular spaces.
Intravascular large B-cell lymphoma. Intravascular large B-cell lymphoma involving a cutaneous haemangioma, showing capillaries distended by tumour cells.
Intravascular large B-cell lymphoma. CD20 immunohistochemistry highlights confinement of tumour cells to vascular spaces in intravascular large B-cell lymphoma involving a cutaneous haemangioma.

Q: A skin biopsy from a patient with fever of unknown origin and peau d'orange lesions shows capillaries massively distended by large, cohesive malignant tumor cells that do not form an extravascular mass. This morphologic presentation is diagnostic of [...].
Intravascular large B-cell lymphoma. An example involving a cutaneous haemangioma.
A: Intravascular Large B-Cell Lymphoma
Back Extra: Intravascular Large B-Cell Lymphoma
- Clinical: Patients often present with fever of unknown origin, pain, and local organ-specific symptoms. The skin is the most commonly affected organ, with diverse dermatological manifestations such as 'peau d’orange'-like lesions and palpable blue-red discolouration.
- Micro: Histopathology shows large lymphoid cells with vesicular nuclei and multiple prominent nucleoli within the lumina of small vessels, often showing mitotic figures. The growth pattern can be free-floating, cohesive, or marginating/adherent.
- Ancillary: Immunophenotype is characterized by CD20 and CD79a positivity. MYD88 and CD79B mutations are common, and IRF4 (MUM1) is positive in 75-80% of cases.
Reference Gallery:
Intravascular large B-cell lymphoma. An example involving a cutaneous haemangioma.
Intravascular large B-cell lymphoma. An example involving a cutaneous haemangioma, highlighted by CD20 immunohistochemistry. Note confinement of tumour cells to vascular spaces in intravascular large B-cell lymphoma.
Intravascular large B-cell lymphoma. High-power magnification shows large tumour cells with vesicular chromatin and several small nucleoli filling vascular spaces.
Intravascular large B-cell lymphoma. Intravascular large B-cell lymphoma involving a cutaneous haemangioma, showing capillaries distended by tumour cells.
Intravascular large B-cell lymphoma. CD20 immunohistochemistry highlights confinement of tumour cells to vascular spaces in intravascular large B-cell lymphoma involving a cutaneous haemangioma.

Q: Histologically, Langerhans Cell Histiocytosis is characterized by an infiltrate of large cells with prominent [...], frequently admixed with inflammatory cells such as eosinophils.
Langerhans cell histiocytosis. Higher-power image of Langerhans cell histiocytosis in papillary dermis with nuclear grooves and mixed inflammatory infiltrate.
Langerhans cell histiocytosis. Langerhans cell histiocytosis cells with typical nuclear grooves and intermixed inflammatory cells including eosinophils.
A: nuclear grooves
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Skin involvement in Langerhans Cell Histiocytosis (LCH) can range from erythematous, crusted, and vesiculopustular lesions to papular nodules with central crusting, often seen in infants.
- Micro: LCH is characterized by the presence of large cells with complex nuclear contours and nuclear grooves, mixed with inflammatory cells including eosinophils and lymphocytes.
- Ancillary: CD1a and CD207 (langerin) immunostaining are key markers for LCH, with CD1a showing membranous staining and CD207 showing granular cytoplasmic staining.
Reference Gallery:
Langerhans cell histiocytosis. Cutaneous Langerhans cell histiocytosis expanding the papillary dermis at the epidermal–dermal interface.
Langerhans cell histiocytosis. Higher-power image of Langerhans cell histiocytosis in papillary dermis with nuclear grooves and mixed inflammatory infiltrate.
Langerhans cell histiocytosis. CD1a stain with membranous staining of Langerhans cell histiocytosis.
Langerhans cell histiocytosis. CD207 (langerin) with cytoplasmic staining.
Langerhans cell histiocytosis. Plump Langerhans cell histiocytosis cells expanding the papillary dermis with epidermotropism.
Langerhans cell histiocytosis. CD207 (langerin) with granular cytoplasmic staining.
Langerhans cell histiocytosis. Expansile dermal expansion of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. CD207 (langerin) with granular cytoplasmic staining including Golgi accentuation (paranuclear, cytoplasmic dot-like) of staining.
Langerhans cell histiocytosis. Langerhans cell histiocytosis cells with typical nuclear grooves and intermixed inflammatory cells including eosinophils.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with expansile dermal infiltrate and epidermotropism and scale crust.
Langerhans cell histiocytosis. Cytoplasmic BRAF VE1 mutant-specific immunostaining in Langerhans cell histiocytosis with known BRAF p.V600E mutation.
Langerhans cell histiocytosis. Langerhans cell histiocytosis involving the scalp of a child.

Q: Immunohistochemically, the lesional cells of Langerhans Cell Histiocytosis are classically positive for membranous CD1a and granular cytoplasmic [...], the latter often showing Golgi accentuation.
Langerhans cell histiocytosis. CD1a stain with membranous staining of Langerhans cell histiocytosis.
Langerhans cell histiocytosis. CD207 (langerin) with granular cytoplasmic staining including Golgi accentuation (paranuclear, cytoplasmic dot-like) of staining.
A: CD207
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Skin involvement in Langerhans Cell Histiocytosis (LCH) can range from erythematous, crusted, and vesiculopustular lesions to papular nodules with central crusting, often seen in infants.
- Micro: LCH is characterized by the presence of large cells with complex nuclear contours and nuclear grooves, mixed with inflammatory cells including eosinophils and lymphocytes.
- Ancillary: CD1a and CD207 (langerin) immunostaining are key markers for LCH, with CD1a showing membranous staining and CD207 showing granular cytoplasmic staining.
Reference Gallery:
Langerhans cell histiocytosis. Cutaneous Langerhans cell histiocytosis expanding the papillary dermis at the epidermal–dermal interface.
Langerhans cell histiocytosis. Higher-power image of Langerhans cell histiocytosis in papillary dermis with nuclear grooves and mixed inflammatory infiltrate.
Langerhans cell histiocytosis. CD1a stain with membranous staining of Langerhans cell histiocytosis.
Langerhans cell histiocytosis. CD207 (langerin) with cytoplasmic staining.
Langerhans cell histiocytosis. Plump Langerhans cell histiocytosis cells expanding the papillary dermis with epidermotropism.
Langerhans cell histiocytosis. CD207 (langerin) with granular cytoplasmic staining.
Langerhans cell histiocytosis. Expansile dermal expansion of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. CD207 (langerin) with granular cytoplasmic staining including Golgi accentuation (paranuclear, cytoplasmic dot-like) of staining.
Langerhans cell histiocytosis. Langerhans cell histiocytosis cells with typical nuclear grooves and intermixed inflammatory cells including eosinophils.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with expansile dermal infiltrate and epidermotropism and scale crust.
Langerhans cell histiocytosis. Cytoplasmic BRAF VE1 mutant-specific immunostaining in Langerhans cell histiocytosis with known BRAF p.V600E mutation.
Langerhans cell histiocytosis. Langerhans cell histiocytosis involving the scalp of a child.

Q: Cutaneous involvement in [...] frequently presents in infants as crusted, vesiculopustular, or papular scalp lesions, and histologically shows an expansile dermal infiltrate with epidermotropism.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with expansile dermal infiltrate and epidermotropism and scale crust.
Langerhans cell histiocytosis. Langerhans cell histiocytosis involving the scalp of a child.
A: Langerhans Cell Histiocytosis
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Skin involvement in Langerhans Cell Histiocytosis (LCH) can range from erythematous, crusted, and vesiculopustular lesions to papular nodules with central crusting, often seen in infants.
- Micro: LCH is characterized by the presence of large cells with complex nuclear contours and nuclear grooves, mixed with inflammatory cells including eosinophils and lymphocytes.
- Ancillary: CD1a and CD207 (langerin) immunostaining are key markers for LCH, with CD1a showing membranous staining and CD207 showing granular cytoplasmic staining.
Reference Gallery:
Langerhans cell histiocytosis. Cutaneous Langerhans cell histiocytosis expanding the papillary dermis at the epidermal–dermal interface.
Langerhans cell histiocytosis. Higher-power image of Langerhans cell histiocytosis in papillary dermis with nuclear grooves and mixed inflammatory infiltrate.
Langerhans cell histiocytosis. CD1a stain with membranous staining of Langerhans cell histiocytosis.
Langerhans cell histiocytosis. CD207 (langerin) with cytoplasmic staining.
Langerhans cell histiocytosis. Plump Langerhans cell histiocytosis cells expanding the papillary dermis with epidermotropism.
Langerhans cell histiocytosis. CD207 (langerin) with granular cytoplasmic staining.
Langerhans cell histiocytosis. Expansile dermal expansion of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. CD207 (langerin) with granular cytoplasmic staining including Golgi accentuation (paranuclear, cytoplasmic dot-like) of staining.
Langerhans cell histiocytosis. Langerhans cell histiocytosis cells with typical nuclear grooves and intermixed inflammatory cells including eosinophils.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with expansile dermal infiltrate and epidermotropism and scale crust.
Langerhans cell histiocytosis. Cytoplasmic BRAF VE1 mutant-specific immunostaining in Langerhans cell histiocytosis with known BRAF p.V600E mutation.
Langerhans cell histiocytosis. Langerhans cell histiocytosis involving the scalp of a child.

Q: Cutaneous involvement by Myeloid Sarcoma frequently presents as a dermal and subcutaneous infiltrate of medium-large monoblasts that typically spares the epidermis, a feature referred to as a [...].
Myeloid sarcoma. Cutaneous involvement by myeloid sarcoma in a patient with a history of acute myeloid leukaemia who presented with an isolated nodular lesion on the right lower back. Diffuse monoblastic infiltrate involves dermis and subcutaneous tissue with sparing of the epidermis (grenz zone). Focally, the neoplastic cells exhibit a single-file pattern of infiltration.
Myeloid sarcoma. Monoblasts are of medium-large size, with fine chromatin, a distinct nucleolus, and a scant to moderate amount of cytoplasm.
A: grenz zone
Back Extra: Myeloid Sarcoma
- Clinical: Myeloid sarcoma can present as violaceous or haemorrhagic papules, plaques, or nodules, and is more common in patients with a history of AML.
- Micro: The neoplastic cells in myeloid sarcoma are medium-large with fine chromatin, a distinct nucleolus, and a scant to moderate amount of cytoplasm.
- Ancillary: Neoplastic cells in myeloid sarcoma express CD13, CD33, CD43, CD68, and myeloperoxidase, and often lack CD34 and KIT.
Reference Gallery:
Myeloid sarcoma. Cutaneous involvement by myeloid sarcoma in a patient with a history of acute myeloid leukaemia who presented with an isolated nodular lesion on the right lower back. Diffuse monoblastic infiltrate involves dermis and subcutaneous tissue with sparing of the epidermis (grenz zone). Focally, the neoplastic cells exhibit a single-file pattern of infiltration.
Myeloid sarcoma. Monoblasts are of medium-large size, with fine chromatin, a distinct nucleolus, and a scant to moderate amount of cytoplasm.
Myeloid sarcoma. Monoblasts express CD68.
Myeloid sarcoma. Monoblasts express lysozyme.
Neoplastic myeloid blast infiltrate. The myeloid blasts have abnormal cytoplasmic NPM1 expression in addition to normal nuclear positivity, indicative of NPM1 mutation. The normal endothelial cells within the vessel have only nuclear-restricted NPM1 expression.
Neoplastic myeloid blast infiltrate, consistent with acute myeloid leukaemia involving skin. Cutaneous involvement by neoplastic myeloid blasts in a patient with acute myeloid leukaemia who presented with a violaceous papular lesion on the left inner thigh. The myeloid blast infiltrate is periadnexal and perivascular and involves the subcutaneous adipose tissue; the epidermis is spared. Given the infiltrate with blasts ≥ 20%, the diagnosis of acute myeloid leukaemia involving skin is most appropriate.

Q: Immunohistochemistry for Myeloid Sarcoma typically demonstrates neoplastic blasts that express myeloid markers such as myeloperoxidase (MPO), lysozyme, and the monocytic/histiocytic marker [...].
Myeloid sarcoma. Monoblasts express CD68.
Myeloid sarcoma. Monoblasts express lysozyme.
A: CD68
Back Extra: Myeloid Sarcoma
- Clinical: Myeloid sarcoma can present as violaceous or haemorrhagic papules, plaques, or nodules, and is more common in patients with a history of AML.
- Micro: The neoplastic cells in myeloid sarcoma are medium-large with fine chromatin, a distinct nucleolus, and a scant to moderate amount of cytoplasm.
- Ancillary: Neoplastic cells in myeloid sarcoma express CD13, CD33, CD43, CD68, and myeloperoxidase, and often lack CD34 and KIT.
Reference Gallery:
Myeloid sarcoma. Cutaneous involvement by myeloid sarcoma in a patient with a history of acute myeloid leukaemia who presented with an isolated nodular lesion on the right lower back. Diffuse monoblastic infiltrate involves dermis and subcutaneous tissue with sparing of the epidermis (grenz zone). Focally, the neoplastic cells exhibit a single-file pattern of infiltration.
Myeloid sarcoma. Monoblasts are of medium-large size, with fine chromatin, a distinct nucleolus, and a scant to moderate amount of cytoplasm.
Myeloid sarcoma. Monoblasts express CD68.
Myeloid sarcoma. Monoblasts express lysozyme.
Neoplastic myeloid blast infiltrate. The myeloid blasts have abnormal cytoplasmic NPM1 expression in addition to normal nuclear positivity, indicative of NPM1 mutation. The normal endothelial cells within the vessel have only nuclear-restricted NPM1 expression.
Neoplastic myeloid blast infiltrate, consistent with acute myeloid leukaemia involving skin. Cutaneous involvement by neoplastic myeloid blasts in a patient with acute myeloid leukaemia who presented with a violaceous papular lesion on the left inner thigh. The myeloid blast infiltrate is periadnexal and perivascular and involves the subcutaneous adipose tissue; the epidermis is spared. Given the infiltrate with blasts ≥ 20%, the diagnosis of acute myeloid leukaemia involving skin is most appropriate.

Q: In cases of Myeloid Sarcoma driven by an NPM1 mutation, immunohistochemistry will reveal abnormal [...] expression of NPM1 in the neoplastic blasts, contrasting with normal nuclear restriction.
Neoplastic myeloid blast infiltrate. The myeloid blasts have abnormal cytoplasmic NPM1 expression in addition to normal nuclear positivity, indicative of NPM1 mutation. The normal endothelial cells within the vessel have only nuclear-restricted NPM1 expression.
A: cytoplasmic
Back Extra: Myeloid Sarcoma
- Clinical: Myeloid sarcoma can present as violaceous or haemorrhagic papules, plaques, or nodules, and is more common in patients with a history of AML.
- Micro: The neoplastic cells in myeloid sarcoma are medium-large with fine chromatin, a distinct nucleolus, and a scant to moderate amount of cytoplasm.
- Ancillary: Neoplastic cells in myeloid sarcoma express CD13, CD33, CD43, CD68, and myeloperoxidase, and often lack CD34 and KIT.
Reference Gallery:
Myeloid sarcoma. Cutaneous involvement by myeloid sarcoma in a patient with a history of acute myeloid leukaemia who presented with an isolated nodular lesion on the right lower back. Diffuse monoblastic infiltrate involves dermis and subcutaneous tissue with sparing of the epidermis (grenz zone). Focally, the neoplastic cells exhibit a single-file pattern of infiltration.
Myeloid sarcoma. Monoblasts are of medium-large size, with fine chromatin, a distinct nucleolus, and a scant to moderate amount of cytoplasm.
Myeloid sarcoma. Monoblasts express CD68.
Myeloid sarcoma. Monoblasts express lysozyme.
Neoplastic myeloid blast infiltrate. The myeloid blasts have abnormal cytoplasmic NPM1 expression in addition to normal nuclear positivity, indicative of NPM1 mutation. The normal endothelial cells within the vessel have only nuclear-restricted NPM1 expression.
Neoplastic myeloid blast infiltrate, consistent with acute myeloid leukaemia involving skin. Cutaneous involvement by neoplastic myeloid blasts in a patient with acute myeloid leukaemia who presented with a violaceous papular lesion on the left inner thigh. The myeloid blast infiltrate is periadnexal and perivascular and involves the subcutaneous adipose tissue; the epidermis is spared. Given the infiltrate with blasts ≥ 20%, the diagnosis of acute myeloid leukaemia involving skin is most appropriate.

Q: Histologically, Lymphomatoid Granulomatosis is characterized by a polymorphous lymphoid infiltrate that displays a distinct [...] pattern, frequently involving small- to large-caliber vessels with associated necrosis.
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. Medium-sized to large hyperchromatic atypical lymphoid cells are arranged in a perivascular pattern.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. Large hyperchromatic atypical lymphoid cells within a necrotic vessel wall and extensive areas of necrosis in the subcutaneous fat.
A: angiocentric and angiodestructive
Back Extra: Lymphomatoid Granulomatosis
- Clinical: Lymphomatoid granulomatosis (LyG) most commonly involves the lung, followed by the CNS (40%) and skin (34%). Cutaneous lesions are frequently disseminated, appearing as multiple erythematous dermal papules or subcutaneous nodules, often with necrosis and ulceration.
- Micro: LyG is characterized by an angiocentric and angiodestructive, polymorphous lymphoid infiltrate with involvement of small- to large-calibre vessels. The lesion contains small lymphocytes admixed with large atypical B cells and often includes areas of necrosis.
- Ancillary: Immunohistochemistry shows the atypical large B cells expressing pan–B-cell markers and being positive for EBV-encoded small RNA (EBER). CD20 is also expressed by the tumour cells, highlighting an angiocentric pattern.
Reference Gallery:
Lymphomatoid granulomatosis, grade 3. Clinical presentation of lymphomatoid granulomatosis, grade 3, with large ulcerating plaques on the back of a 57-year-old female patient, who presented with extensive skin lesions and a cerebellar involvement.
Lymphomatoid granulomatosis, grade 3. Clinical presentation of lymphomatoid granulomatosis, grade 3, with large ulcerating plaques on the chest of a 57-year-old female patient, who presented with extensive skin lesions and a cerebellar involvement.
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. A lymphocytic infiltrate is seen in the dermis, with a perivascular pattern.
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. The large cells are positive for EBV by in situ hybridization for EBV-encoded small RNA (EBER).
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. Medium-sized to large hyperchromatic atypical lymphoid cells are arranged in a perivascular pattern.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. Large hyperchromatic atypical lymphoid cells within a necrotic vessel wall and extensive areas of necrosis in the subcutaneous fat.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. EBV-encoded small RNA (EBER) immunohistochemical expression by the tumour cells highlights an angiocentric pattern.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. CD20 is expressed by the tumour cells and highlights an angiocentric pattern.

Q: In Lymphomatoid Granulomatosis, the large, atypical B cells are characteristically positive for [...], which is typically demonstrated using EBER in situ hybridization.
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. The large cells are positive for EBV by in situ hybridization for EBV-encoded small RNA (EBER).
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. EBV-encoded small RNA (EBER) immunohistochemical expression by the tumour cells highlights an angiocentric pattern.
A: Epstein-Barr virus (EBV)
Back Extra: Lymphomatoid Granulomatosis
- Clinical: Lymphomatoid granulomatosis (LyG) most commonly involves the lung, followed by the CNS (40%) and skin (34%). Cutaneous lesions are frequently disseminated, appearing as multiple erythematous dermal papules or subcutaneous nodules, often with necrosis and ulceration.
- Micro: LyG is characterized by an angiocentric and angiodestructive, polymorphous lymphoid infiltrate with involvement of small- to large-calibre vessels. The lesion contains small lymphocytes admixed with large atypical B cells and often includes areas of necrosis.
- Ancillary: Immunohistochemistry shows the atypical large B cells expressing pan–B-cell markers and being positive for EBV-encoded small RNA (EBER). CD20 is also expressed by the tumour cells, highlighting an angiocentric pattern.
Reference Gallery:
Lymphomatoid granulomatosis, grade 3. Clinical presentation of lymphomatoid granulomatosis, grade 3, with large ulcerating plaques on the back of a 57-year-old female patient, who presented with extensive skin lesions and a cerebellar involvement.
Lymphomatoid granulomatosis, grade 3. Clinical presentation of lymphomatoid granulomatosis, grade 3, with large ulcerating plaques on the chest of a 57-year-old female patient, who presented with extensive skin lesions and a cerebellar involvement.
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. A lymphocytic infiltrate is seen in the dermis, with a perivascular pattern.
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. The large cells are positive for EBV by in situ hybridization for EBV-encoded small RNA (EBER).
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. Medium-sized to large hyperchromatic atypical lymphoid cells are arranged in a perivascular pattern.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. Large hyperchromatic atypical lymphoid cells within a necrotic vessel wall and extensive areas of necrosis in the subcutaneous fat.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. EBV-encoded small RNA (EBER) immunohistochemical expression by the tumour cells highlights an angiocentric pattern.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. CD20 is expressed by the tumour cells and highlights an angiocentric pattern.

Q: Cutaneous lesions of Lymphomatoid Granulomatosis frequently disseminate and present as multiple erythematous dermal papules or subcutaneous nodules, often progressing to prominent [...].
Lymphomatoid granulomatosis, grade 3. Clinical presentation of lymphomatoid granulomatosis, grade 3, with large ulcerating plaques on the back of a 57-year-old female patient, who presented with extensive skin lesions and a cerebellar involvement.
Lymphomatoid granulomatosis, grade 3. Clinical presentation of lymphomatoid granulomatosis, grade 3, with large ulcerating plaques on the chest of a 57-year-old female patient, who presented with extensive skin lesions and a cerebellar involvement.
A: necrosis and ulceration
Back Extra: Lymphomatoid Granulomatosis
- Clinical: Lymphomatoid granulomatosis (LyG) most commonly involves the lung, followed by the CNS (40%) and skin (34%). Cutaneous lesions are frequently disseminated, appearing as multiple erythematous dermal papules or subcutaneous nodules, often with necrosis and ulceration.
- Micro: LyG is characterized by an angiocentric and angiodestructive, polymorphous lymphoid infiltrate with involvement of small- to large-calibre vessels. The lesion contains small lymphocytes admixed with large atypical B cells and often includes areas of necrosis.
- Ancillary: Immunohistochemistry shows the atypical large B cells expressing pan–B-cell markers and being positive for EBV-encoded small RNA (EBER). CD20 is also expressed by the tumour cells, highlighting an angiocentric pattern.
Reference Gallery:
Lymphomatoid granulomatosis, grade 3. Clinical presentation of lymphomatoid granulomatosis, grade 3, with large ulcerating plaques on the back of a 57-year-old female patient, who presented with extensive skin lesions and a cerebellar involvement.
Lymphomatoid granulomatosis, grade 3. Clinical presentation of lymphomatoid granulomatosis, grade 3, with large ulcerating plaques on the chest of a 57-year-old female patient, who presented with extensive skin lesions and a cerebellar involvement.
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. A lymphocytic infiltrate is seen in the dermis, with a perivascular pattern.
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. The large cells are positive for EBV by in situ hybridization for EBV-encoded small RNA (EBER).
Lymphomatoid granulomatosis, grade 2. A 56-year-old woman presenting with clusters of erythematous papules on the trunk. Medium-sized to large hyperchromatic atypical lymphoid cells are arranged in a perivascular pattern.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. Large hyperchromatic atypical lymphoid cells within a necrotic vessel wall and extensive areas of necrosis in the subcutaneous fat.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. EBV-encoded small RNA (EBER) immunohistochemical expression by the tumour cells highlights an angiocentric pattern.
Lymphomatoid granulomatosis, grade 3. A 72-year-old male patient presenting with various large ulcerating plaques. CD20 is expressed by the tumour cells and highlights an angiocentric pattern.

Q: Clinically, Lymphomatoid Papulosis presents with recurrent papulonodular skin lesions that characteristically exhibit a [...] course, often spontaneously ulcerating and regressing to leave scars.
Lymphomatoid papulosis. Papules and small nodules, as well as hyperpigmented macules as residuals of regressed lesions on the leg.
A: waxing and waning
Back Extra: Lymphomatoid Papulosis
- Clinical: Lymphomatoid papulosis (LyP) is characterized by recurrent waxing and waning papulonodular skin lesions that may ulcerate and leave scars or pigmentary changes.
- Micro: Histologically, LyP features atypical CD30-positive T cells in a mixed inflammatory background, with distinct subtypes (A, B, C, D, E) showing varying cellular and architectural patterns.
- Ancillary: Monoclonal T-cell receptor (TR) gene rearrangements are detectable in 22–80% of cases, and the DUSP22-IRF4 locus rearrangement is found in a small subset of cases.
Reference Gallery:
Lymphomatoid papulosis. Papules and small nodules, as well as hyperpigmented macules as residuals of regressed lesions on the leg.
Lymphomatoid papulosis. Wedge-shaped infiltrate of atypical lymphoid cells beneath an ulceration.
Lymphomatoid papulosis, subtype C. Cohesive infiltrates of medium-sized to large lymphoid cells.
Lymphomatoid papulosis, subtype C. Infiltrates of large lymphoid cells with severe nuclear pleomorphism.
Lymphomatoid papulosis, subtype C. Expression of CD30 by all atypical cells (red substrate).
Lymphomatoid papulosis, subtype A. Mixed infiltrate of scattered medium-sized to large lymphoid cells within a background of small lymphocytes and histiocytes.
Lymphomatoid papulosis, subtype A. Mixed infiltrate of scattered medium-sized to large lymphoid cells within a background of eosinophils, small lymphocytes, and histiocytes.
Lymphomatoid papulosis, subtype A. Expression of CD30 by all atypical cells (red substrate).
Lymphomatoid papulosis, subtype B. Epidermotropic infiltrate of small, slightly atypical lymphocytes, which express CD4 and (variably) CD30.
Lymphomatoid papulosis, subtype D. Epidermotropic infiltrate of small to medium-sized atypical lymphocytes.
Lymphomatoid papulosis, subtype D. Expression of CD30 by epidermotropic and dermal atypical lymphocytes (red substrate).
Lymphomatoid papulosis, subtype E. Angiocentric and angiodestructive infiltrates of medium-sized lymphoid cells with pleomorphic nuclei.

Q: Regardless of the histologic subtype, the atypical T cells in Lymphomatoid Papulosis characteristically show strong expression of [...] on immunohistochemistry.
Lymphomatoid papulosis, subtype C. Expression of CD30 by all atypical cells (red substrate).
Lymphomatoid papulosis, subtype A. Expression of CD30 by all atypical cells (red substrate).
A: CD30
Back Extra: Lymphomatoid Papulosis
- Clinical: Lymphomatoid papulosis (LyP) is characterized by recurrent waxing and waning papulonodular skin lesions that may ulcerate and leave scars or pigmentary changes.
- Micro: Histologically, LyP features atypical CD30-positive T cells in a mixed inflammatory background, with distinct subtypes (A, B, C, D, E) showing varying cellular and architectural patterns.
- Ancillary: Monoclonal T-cell receptor (TR) gene rearrangements are detectable in 22–80% of cases, and the DUSP22-IRF4 locus rearrangement is found in a small subset of cases.
Reference Gallery:
Lymphomatoid papulosis. Papules and small nodules, as well as hyperpigmented macules as residuals of regressed lesions on the leg.
Lymphomatoid papulosis. Wedge-shaped infiltrate of atypical lymphoid cells beneath an ulceration.
Lymphomatoid papulosis, subtype C. Cohesive infiltrates of medium-sized to large lymphoid cells.
Lymphomatoid papulosis, subtype C. Infiltrates of large lymphoid cells with severe nuclear pleomorphism.
Lymphomatoid papulosis, subtype C. Expression of CD30 by all atypical cells (red substrate).
Lymphomatoid papulosis, subtype A. Mixed infiltrate of scattered medium-sized to large lymphoid cells within a background of small lymphocytes and histiocytes.
Lymphomatoid papulosis, subtype A. Mixed infiltrate of scattered medium-sized to large lymphoid cells within a background of eosinophils, small lymphocytes, and histiocytes.
Lymphomatoid papulosis, subtype A. Expression of CD30 by all atypical cells (red substrate).
Lymphomatoid papulosis, subtype B. Epidermotropic infiltrate of small, slightly atypical lymphocytes, which express CD4 and (variably) CD30.
Lymphomatoid papulosis, subtype D. Epidermotropic infiltrate of small to medium-sized atypical lymphocytes.
Lymphomatoid papulosis, subtype D. Expression of CD30 by epidermotropic and dermal atypical lymphocytes (red substrate).
Lymphomatoid papulosis, subtype E. Angiocentric and angiodestructive infiltrates of medium-sized lymphoid cells with pleomorphic nuclei.

Q: At low magnification, Lymphomatoid Papulosis often displays a classic [...] dermal infiltrate of atypical lymphoid cells, typically situated beneath an epidermal ulceration.
Lymphomatoid papulosis. Wedge-shaped infiltrate of atypical lymphoid cells beneath an ulceration.
A: wedge-shaped
Back Extra: Lymphomatoid Papulosis
- Clinical: Lymphomatoid papulosis (LyP) is characterized by recurrent waxing and waning papulonodular skin lesions that may ulcerate and leave scars or pigmentary changes.
- Micro: Histologically, LyP features atypical CD30-positive T cells in a mixed inflammatory background, with distinct subtypes (A, B, C, D, E) showing varying cellular and architectural patterns.
- Ancillary: Monoclonal T-cell receptor (TR) gene rearrangements are detectable in 22–80% of cases, and the DUSP22-IRF4 locus rearrangement is found in a small subset of cases.
Reference Gallery:
Lymphomatoid papulosis. Papules and small nodules, as well as hyperpigmented macules as residuals of regressed lesions on the leg.
Lymphomatoid papulosis. Wedge-shaped infiltrate of atypical lymphoid cells beneath an ulceration.
Lymphomatoid papulosis, subtype C. Cohesive infiltrates of medium-sized to large lymphoid cells.
Lymphomatoid papulosis, subtype C. Infiltrates of large lymphoid cells with severe nuclear pleomorphism.
Lymphomatoid papulosis, subtype C. Expression of CD30 by all atypical cells (red substrate).
Lymphomatoid papulosis, subtype A. Mixed infiltrate of scattered medium-sized to large lymphoid cells within a background of small lymphocytes and histiocytes.
Lymphomatoid papulosis, subtype A. Mixed infiltrate of scattered medium-sized to large lymphoid cells within a background of eosinophils, small lymphocytes, and histiocytes.
Lymphomatoid papulosis, subtype A. Expression of CD30 by all atypical cells (red substrate).
Lymphomatoid papulosis, subtype B. Epidermotropic infiltrate of small, slightly atypical lymphocytes, which express CD4 and (variably) CD30.
Lymphomatoid papulosis, subtype D. Epidermotropic infiltrate of small to medium-sized atypical lymphocytes.
Lymphomatoid papulosis, subtype D. Expression of CD30 by epidermotropic and dermal atypical lymphocytes (red substrate).
Lymphomatoid papulosis, subtype E. Angiocentric and angiodestructive infiltrates of medium-sized lymphoid cells with pleomorphic nuclei.

Q: The diagnosis of Mantle Cell Lymphoma is confirmed by a CD20+, CD5+, and CD23- immunophenotype along with uniform nuclear overexpression of [...].
Mantle cell lymphoma. Strong membrane expression of CD20 by immunohistochemistry.
Mantle cell lymphoma. Strong nuclear expression of cyclin D1 by immunohistochemistry.
A: cyclin D1
Back Extra: Mantle Cell Lymphoma
- Clinical: Mantle cell lymphoma (MCL) typically presents as skin nodules, plaques, or macular lesions, usually in older adults and more commonly in men.
- Micro: MCL shows a nodular, diffuse, or perivascular and periadnexal dermal infiltrate separated from the epidermis by a grenz zone. The blastoid subtype is characterized by medium-sized cells with dispersed chromatin and frequent mitoses.
- Ancillary: Diagnosis of MCL is confirmed by uniform nuclear overexpression of cyclin D1, and the immunophenotype is typically CD20+, CD5+, CD10−, BCL6−, BCL2+, CD23−, and cyclin D1+.
Reference Gallery:
Mantle cell lymphoma. Skin infiltration by a mantle cell lymphoma presenting as a confluent nodular lesion at the lower leg – thus clinically mimicking a primary cutaneous diffuse large B-cell lymphoma, leg type.
Mantle cell lymphoma (blastoid subtype). Involving skin. This patient relapsed with widespread disease 6 years after being diagnosed with mantle cell lymphoma and after receiving aggressive therapy including bone marrow transplant. There is a diffuse dermal proliferation of blastoid cells separated from the epidermis by a grenz zone of uninvolved papillary dermis. The patient died within 1 week of this skin biopsy.
Mantle cell lymphoma (blastoid subtype). The neoplastic cells are mitotically active, medium-sized atypical cells with oval and irregular nuclei, finely dispersed chromatin, occasional small nucleoli, and scant cytoplasm.
Mantle cell lymphoma. Strong membrane expression of CD20 by immunohistochemistry.
Mantle cell lymphoma. Strong nuclear expression of cyclin D1 by immunohistochemistry.

Q: In cutaneous involvement by Mantle Cell Lymphoma, the dermal infiltrate is characteristically separated from the epidermis by an uninvolved area of papillary dermis known as a [...].
Mantle cell lymphoma (blastoid subtype). Involving skin. This patient relapsed with widespread disease 6 years after being diagnosed with mantle cell lymphoma and after receiving aggressive therapy including bone marrow transplant. There is a diffuse dermal proliferation of blastoid cells separated from the epidermis by a grenz zone of uninvolved papillary dermis. The patient died within 1 week of this skin biopsy.
Mantle cell lymphoma (blastoid subtype). The neoplastic cells are mitotically active, medium-sized atypical cells with oval and irregular nuclei, finely dispersed chromatin, occasional small nucleoli, and scant cytoplasm.
A: grenz zone
Back Extra: Mantle Cell Lymphoma
- Clinical: Mantle cell lymphoma (MCL) typically presents as skin nodules, plaques, or macular lesions, usually in older adults and more commonly in men.
- Micro: MCL shows a nodular, diffuse, or perivascular and periadnexal dermal infiltrate separated from the epidermis by a grenz zone. The blastoid subtype is characterized by medium-sized cells with dispersed chromatin and frequent mitoses.
- Ancillary: Diagnosis of MCL is confirmed by uniform nuclear overexpression of cyclin D1, and the immunophenotype is typically CD20+, CD5+, CD10−, BCL6−, BCL2+, CD23−, and cyclin D1+.
Reference Gallery:
Mantle cell lymphoma. Skin infiltration by a mantle cell lymphoma presenting as a confluent nodular lesion at the lower leg – thus clinically mimicking a primary cutaneous diffuse large B-cell lymphoma, leg type.
Mantle cell lymphoma (blastoid subtype). Involving skin. This patient relapsed with widespread disease 6 years after being diagnosed with mantle cell lymphoma and after receiving aggressive therapy including bone marrow transplant. There is a diffuse dermal proliferation of blastoid cells separated from the epidermis by a grenz zone of uninvolved papillary dermis. The patient died within 1 week of this skin biopsy.
Mantle cell lymphoma (blastoid subtype). The neoplastic cells are mitotically active, medium-sized atypical cells with oval and irregular nuclei, finely dispersed chromatin, occasional small nucleoli, and scant cytoplasm.
Mantle cell lymphoma. Strong membrane expression of CD20 by immunohistochemistry.
Mantle cell lymphoma. Strong nuclear expression of cyclin D1 by immunohistochemistry.

Q: Microscopically, Mast Cell Sarcoma presents as a localized tumor of immature, highly atypical cells that are often accompanied by a prominent background infiltrate of [...].
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei (shown here). The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
A: eosinophils
Back Extra: Mast Cell Sarcoma
- Clinical: Mast Cell Sarcoma (MCS) arises de novo in most cases, and up to 30% of patients present with symptoms of mast cell activation syndrome, including flushing, fever, malaise, diarrhoea, and tachycardia.
- Micro: MCS manifests as a localized tumour of immature and often highly atypical cells with a destructive growth pattern, containing metachromatic granules and often infiltrated by eosinophils.
- Ancillary: Neoplastic mast cells in MCS express tryptase and KIT (CD117), and may variably express CD2, CD25, and CD30. Whole KIT sequencing is recommended due to the low frequency of the typical KIT p.D816V mutation.
Reference Gallery:
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25 (shown here), and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117) (shown here), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found (shown here). The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa) (shown here). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei (shown here). The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.

Q: Neoplastic cells in Mast Cell Sarcoma characteristically contain [...] granules that can be highlighted by a Giemsa stain.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa) (shown here). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
A: metachromatic
Back Extra: Mast Cell Sarcoma
- Clinical: Mast Cell Sarcoma (MCS) arises de novo in most cases, and up to 30% of patients present with symptoms of mast cell activation syndrome, including flushing, fever, malaise, diarrhoea, and tachycardia.
- Micro: MCS manifests as a localized tumour of immature and often highly atypical cells with a destructive growth pattern, containing metachromatic granules and often infiltrated by eosinophils.
- Ancillary: Neoplastic mast cells in MCS express tryptase and KIT (CD117), and may variably express CD2, CD25, and CD30. Whole KIT sequencing is recommended due to the low frequency of the typical KIT p.D816V mutation.
Reference Gallery:
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25 (shown here), and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117) (shown here), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found (shown here). The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa) (shown here). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei (shown here). The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.

Q: While Mast Cell Sarcoma strongly expresses KIT (CD117), it has a low frequency of the classic [...] mutation commonly seen in systemic mastocytosis, therefore whole KIT sequencing is recommended.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117) (shown here), CD25, and CD30.
A: p.D816V
Back Extra: Mast Cell Sarcoma
- Clinical: Mast Cell Sarcoma (MCS) arises de novo in most cases, and up to 30% of patients present with symptoms of mast cell activation syndrome, including flushing, fever, malaise, diarrhoea, and tachycardia.
- Micro: MCS manifests as a localized tumour of immature and often highly atypical cells with a destructive growth pattern, containing metachromatic granules and often infiltrated by eosinophils.
- Ancillary: Neoplastic mast cells in MCS express tryptase and KIT (CD117), and may variably express CD2, CD25, and CD30. Whole KIT sequencing is recommended due to the low frequency of the typical KIT p.D816V mutation.
Reference Gallery:
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25 (shown here), and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117) (shown here), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found (shown here). The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei. The tumour cells show metachromatic granules (Giemsa) (shown here). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.
Mast cell sarcoma. Mast cell sarcoma of the rib in a 73-year-old male patient. At high magnification, highly polymorphic tumour cells lay in a background of numerous eosinophils; some neoplastic cells present with bilobated nuclei (shown here). The tumour cells show metachromatic granules (Giemsa). A pronounced cytoplasmic expression of tryptase was found. The tumour cells showed a strong membranous expression of KIT (CD117), CD25, and CD30.

Q: In Mastocytosis, the neoplastic cells classically contain numerous cytoplasmic metachromatic granules that are intensely highlighted by a [...] stain.
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (<<38203>>). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (shown here). A moderate cytoplasmic expression of tryptase is evident (<<38205>>). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).
A: Giemsa
Back Extra: Mastocytosis
- Clinical: Cutaneous mastocytosis often presents with maculopapular lesions, which are typically brown or red and can be pruritic. Systemic symptoms like flushing, headache, and diarrhea are due to mast cell mediator release.
- Micro: Histopathologically, cutaneous mastocytosis shows an increase in dermal mast cells, often with a spindle-shaped morphology. Immunohistochemistry for tryptase and KIT (CD117) is positive in these cells.
- Ancillary: Diagnosis of mastocytosis is supported by the detection of KIT mutations, particularly p.D816V, and the presence of aberrant immunophenotypes such as CD25+ or CD2+ mast cells in lesional skin.
Reference Gallery:
Cutaneous mastocytosis. Mastocytosis in the skin in an adult with the clinical picture of cutaneous mastocytosis (monomorphic maculopapular cutaneous mastocytosis). Immunohistochemistry for tryptase shows a moderate increase in mostly spindle-shaped mast cells. Only a few neoplastic mast cells show an aberrant expression of CD25 (not pictured). A bone marrow biopsy is indicated in this situation, because more than 90% of adult patients with the preliminary diagnosis of mastocytosis in the skin have systemic mastocytosis, usually indolent systemic mastocytosis.
Cutaneous mastocytosis. Clinical presentation of polymorphic maculopapular cutaneous mastocytosis (shown here), monomorphic maculopapular cutaneous mastocytosis (<<38199>>), and diffuse cutaneous mastocytosis (<<38200>>).
Cutaneous mastocytosis. Clinical presentation of polymorphic maculopapular cutaneous mastocytosis (<<38198>>), monomorphic maculopapular cutaneous mastocytosis (shown here), and diffuse cutaneous mastocytosis (<<38200>>).
Cutaneous mastocytosis. Clinical presentation of polymorphic maculopapular cutaneous mastocytosis (<<38198>>), monomorphic maculopapular cutaneous mastocytosis (<<38199>>), and diffuse cutaneous mastocytosis (shown here).
Paediatric cutaneous mastocytosis (polymorphic maculopapular cutaneous mastocytosis). The epidermis shows elongated rete ridges and pronounced hyperpigmentation. Pale-staining histiocytoid cells infiltrate the upper dermis. Immunohistochemistry for tryptase (<<38202>>) identifies these cells as mast cells.
Paediatric cutaneous mastocytosis (polymorphic maculopapular cutaneous mastocytosis). The epidermis shows elongated rete ridges and pronounced hyperpigmentation. Pale-staining histiocytoid cells infiltrate the upper dermis (<<38201>>). Immunohistochemistry for tryptase (shone here) identifies these cells as mast cells.
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (shown here). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (<<38204>>). A moderate cytoplasmic expression of tryptase is evident (<<38205>>). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (<<38203>>). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (shown here). A moderate cytoplasmic expression of tryptase is evident (<<38205>>). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (<<38203>>). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (<<38204>>). A moderate cytoplasmic expression of tryptase is evident (shown here). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).

Q: The diagnosis of Mastocytosis is confirmed histologically by an increase in dermal spindle-shaped or histiocytoid cells that demonstrate strong immunohistochemical positivity for KIT (CD117) and [...].
Cutaneous mastocytosis. Mastocytosis in the skin in an adult with the clinical picture of cutaneous mastocytosis (monomorphic maculopapular cutaneous mastocytosis). Immunohistochemistry for tryptase shows a moderate increase in mostly spindle-shaped mast cells. Only a few neoplastic mast cells show an aberrant expression of CD25 (not pictured). A bone marrow biopsy is indicated in this situation, because more than 90% of adult patients with the preliminary diagnosis of mastocytosis in the skin have systemic mastocytosis, usually indolent systemic mastocytosis.
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (<<38203>>). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (<<38204>>). A moderate cytoplasmic expression of tryptase is evident (shown here). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).
A: tryptase
Back Extra: Mastocytosis
- Clinical: Cutaneous mastocytosis often presents with maculopapular lesions, which are typically brown or red and can be pruritic. Systemic symptoms like flushing, headache, and diarrhea are due to mast cell mediator release.
- Micro: Histopathologically, cutaneous mastocytosis shows an increase in dermal mast cells, often with a spindle-shaped morphology. Immunohistochemistry for tryptase and KIT (CD117) is positive in these cells.
- Ancillary: Diagnosis of mastocytosis is supported by the detection of KIT mutations, particularly p.D816V, and the presence of aberrant immunophenotypes such as CD25+ or CD2+ mast cells in lesional skin.
Reference Gallery:
Cutaneous mastocytosis. Mastocytosis in the skin in an adult with the clinical picture of cutaneous mastocytosis (monomorphic maculopapular cutaneous mastocytosis). Immunohistochemistry for tryptase shows a moderate increase in mostly spindle-shaped mast cells. Only a few neoplastic mast cells show an aberrant expression of CD25 (not pictured). A bone marrow biopsy is indicated in this situation, because more than 90% of adult patients with the preliminary diagnosis of mastocytosis in the skin have systemic mastocytosis, usually indolent systemic mastocytosis.
Cutaneous mastocytosis. Clinical presentation of polymorphic maculopapular cutaneous mastocytosis (shown here), monomorphic maculopapular cutaneous mastocytosis (<<38199>>), and diffuse cutaneous mastocytosis (<<38200>>).
Cutaneous mastocytosis. Clinical presentation of polymorphic maculopapular cutaneous mastocytosis (<<38198>>), monomorphic maculopapular cutaneous mastocytosis (shown here), and diffuse cutaneous mastocytosis (<<38200>>).
Cutaneous mastocytosis. Clinical presentation of polymorphic maculopapular cutaneous mastocytosis (<<38198>>), monomorphic maculopapular cutaneous mastocytosis (<<38199>>), and diffuse cutaneous mastocytosis (shown here).
Paediatric cutaneous mastocytosis (polymorphic maculopapular cutaneous mastocytosis). The epidermis shows elongated rete ridges and pronounced hyperpigmentation. Pale-staining histiocytoid cells infiltrate the upper dermis. Immunohistochemistry for tryptase (<<38202>>) identifies these cells as mast cells.
Paediatric cutaneous mastocytosis (polymorphic maculopapular cutaneous mastocytosis). The epidermis shows elongated rete ridges and pronounced hyperpigmentation. Pale-staining histiocytoid cells infiltrate the upper dermis (<<38201>>). Immunohistochemistry for tryptase (shone here) identifies these cells as mast cells.
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (shown here). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (<<38204>>). A moderate cytoplasmic expression of tryptase is evident (<<38205>>). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (<<38203>>). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (shown here). A moderate cytoplasmic expression of tryptase is evident (<<38205>>). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (<<38203>>). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (<<38204>>). A moderate cytoplasmic expression of tryptase is evident (shown here). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).

Q: In adult patients presenting with cutaneous Mastocytosis, the neoplastic cells may show aberrant expression of [...], which strongly correlates with systemic disease and indicates the need for a bone marrow biopsy.
Cutaneous mastocytosis. Mastocytosis in the skin in an adult with the clinical picture of cutaneous mastocytosis (monomorphic maculopapular cutaneous mastocytosis). Immunohistochemistry for tryptase shows a moderate increase in mostly spindle-shaped mast cells. Only a few neoplastic mast cells show an aberrant expression of CD25 (not pictured). A bone marrow biopsy is indicated in this situation, because more than 90% of adult patients with the preliminary diagnosis of mastocytosis in the skin have systemic mastocytosis, usually indolent systemic mastocytosis.
A: CD25
Back Extra: Mastocytosis
- Clinical: Cutaneous mastocytosis often presents with maculopapular lesions, which are typically brown or red and can be pruritic. Systemic symptoms like flushing, headache, and diarrhea are due to mast cell mediator release.
- Micro: Histopathologically, cutaneous mastocytosis shows an increase in dermal mast cells, often with a spindle-shaped morphology. Immunohistochemistry for tryptase and KIT (CD117) is positive in these cells.
- Ancillary: Diagnosis of mastocytosis is supported by the detection of KIT mutations, particularly p.D816V, and the presence of aberrant immunophenotypes such as CD25+ or CD2+ mast cells in lesional skin.
Reference Gallery:
Cutaneous mastocytosis. Mastocytosis in the skin in an adult with the clinical picture of cutaneous mastocytosis (monomorphic maculopapular cutaneous mastocytosis). Immunohistochemistry for tryptase shows a moderate increase in mostly spindle-shaped mast cells. Only a few neoplastic mast cells show an aberrant expression of CD25 (not pictured). A bone marrow biopsy is indicated in this situation, because more than 90% of adult patients with the preliminary diagnosis of mastocytosis in the skin have systemic mastocytosis, usually indolent systemic mastocytosis.
Cutaneous mastocytosis. Clinical presentation of polymorphic maculopapular cutaneous mastocytosis (shown here), monomorphic maculopapular cutaneous mastocytosis (<<38199>>), and diffuse cutaneous mastocytosis (<<38200>>).
Cutaneous mastocytosis. Clinical presentation of polymorphic maculopapular cutaneous mastocytosis (<<38198>>), monomorphic maculopapular cutaneous mastocytosis (shown here), and diffuse cutaneous mastocytosis (<<38200>>).
Cutaneous mastocytosis. Clinical presentation of polymorphic maculopapular cutaneous mastocytosis (<<38198>>), monomorphic maculopapular cutaneous mastocytosis (<<38199>>), and diffuse cutaneous mastocytosis (shown here).
Paediatric cutaneous mastocytosis (polymorphic maculopapular cutaneous mastocytosis). The epidermis shows elongated rete ridges and pronounced hyperpigmentation. Pale-staining histiocytoid cells infiltrate the upper dermis. Immunohistochemistry for tryptase (<<38202>>) identifies these cells as mast cells.
Paediatric cutaneous mastocytosis (polymorphic maculopapular cutaneous mastocytosis). The epidermis shows elongated rete ridges and pronounced hyperpigmentation. Pale-staining histiocytoid cells infiltrate the upper dermis (<<38201>>). Immunohistochemistry for tryptase (shone here) identifies these cells as mast cells.
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (shown here). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (<<38204>>). A moderate cytoplasmic expression of tryptase is evident (<<38205>>). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (<<38203>>). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (shown here). A moderate cytoplasmic expression of tryptase is evident (<<38205>>). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).
Mastocytoma. Sheets of isomorphic round cells with histiocytoid appearance are seen expanding the dermis (<<38203>>). The neoplastic cells show numerous cytoplasmic metachromatic granules (Giemsa) (<<38204>>). A moderate cytoplasmic expression of tryptase is evident (shown here). In addition, the neoplastic mast cells demonstrate a strong membranous expression of KIT (CD117) (<<38206>>). Of note, no expression of CD25 and no KIT mutations were found (neither p.D816V nor mutations in other relevant regions of the KIT gene).

Q: Histologically, Reticulohistiocytosis features a dermal infiltrate of large, often multinucleated giant cells characterized by abundant, eosinophilic, [...] cytoplasm.
Multicentric reticulohistiocytosis. Dermal infiltrate made of multinuclear ground-glass histiocytes.
Solitary reticulohistiocytoma. Upper dermal infiltrate made of mononucleate to multinucleate histiocytes with eosinophilic ground-glass cytoplasm.
Diffuse reticulohistiocytosis. At higher magnification, the infiltrate is made of large to giant epithelioid cells with single or multiple randomly oriented nuclei and abundant eosinophilic “ground-glass” cytoplasm. Rare figures of emperipolesis may be seen.
A: ground-glass
Back Extra: Reticulohistiocytosis
- Clinical: Reticulohistiocytosis can present as a solitary cutaneous lesion (reticulohistiocytoma) or as multiple lesions (multicentric reticulohistiocytosis), often associated with erosive polyarthritis.
- Micro: Histologically, reticulohistiocytosis is characterized by a dermal infiltrate of large mononuclear, binucleated, or multinucleated giant cells with randomly oriented nuclei and finely granular ground-glass cytoplasm.
- Ancillary: The histiocytes in reticulohistiocytosis are positive for CD14, CD68 (KP1 and PGM1), CD163, and vimentin, and negative for CD1a and CD207 (langerin).
Reference Gallery:
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). A single papular-nodular erythematous cutaneous lesion.
Multicentric reticulohistiocytosis. Multiple papular lesions over the hand joints.
Multicentric reticulohistiocytosis. Dermal infiltrate made of multinuclear ground-glass histiocytes.
Solitary reticulohistiocytoma. Upper dermal infiltrate made of mononucleate to multinucleate histiocytes with eosinophilic ground-glass cytoplasm.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). Tumour cells express CD68R/PGM1.
Diffuse reticulohistiocytosis. At higher magnification, the infiltrate is made of large to giant epithelioid cells with single or multiple randomly oriented nuclei and abundant eosinophilic “ground-glass” cytoplasm. Rare figures of emperipolesis may be seen.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The dome-shaped skin lesion comprises a dense infiltrate of large histiocytes in the dermis.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The histiocytes are very large and show prominent nucleoli and abundant hyaline cytoplasm.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The histiocytes are immunoreactive for CD163.
Solitary cutaneous reticulohistiocytoma. The histiocytes are negative for S100.
Solitary cutaneous reticulohistiocytoma. A dome-shaped skin lesion formed by a dense dermal infiltrate of large histiocytes.
Solitary cutaneous reticulohistiocytoma. In this example, most histiocytes are multinucleated. They have abundant eosinophilic cytoplasm, sometimes with fine vacuoles.

Q: Patients with the multicentric form of Reticulohistiocytosis often present with multiple cutaneous papules and nodules that are strongly associated with severe, [...].
Multicentric reticulohistiocytosis. Multiple papular lesions over the hand joints.
A: erosive polyarthritis
Back Extra: Reticulohistiocytosis
- Clinical: Reticulohistiocytosis can present as a solitary cutaneous lesion (reticulohistiocytoma) or as multiple lesions (multicentric reticulohistiocytosis), often associated with erosive polyarthritis.
- Micro: Histologically, reticulohistiocytosis is characterized by a dermal infiltrate of large mononuclear, binucleated, or multinucleated giant cells with randomly oriented nuclei and finely granular ground-glass cytoplasm.
- Ancillary: The histiocytes in reticulohistiocytosis are positive for CD14, CD68 (KP1 and PGM1), CD163, and vimentin, and negative for CD1a and CD207 (langerin).
Reference Gallery:
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). A single papular-nodular erythematous cutaneous lesion.
Multicentric reticulohistiocytosis. Multiple papular lesions over the hand joints.
Multicentric reticulohistiocytosis. Dermal infiltrate made of multinuclear ground-glass histiocytes.
Solitary reticulohistiocytoma. Upper dermal infiltrate made of mononucleate to multinucleate histiocytes with eosinophilic ground-glass cytoplasm.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). Tumour cells express CD68R/PGM1.
Diffuse reticulohistiocytosis. At higher magnification, the infiltrate is made of large to giant epithelioid cells with single or multiple randomly oriented nuclei and abundant eosinophilic “ground-glass” cytoplasm. Rare figures of emperipolesis may be seen.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The dome-shaped skin lesion comprises a dense infiltrate of large histiocytes in the dermis.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The histiocytes are very large and show prominent nucleoli and abundant hyaline cytoplasm.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The histiocytes are immunoreactive for CD163.
Solitary cutaneous reticulohistiocytoma. The histiocytes are negative for S100.
Solitary cutaneous reticulohistiocytoma. A dome-shaped skin lesion formed by a dense dermal infiltrate of large histiocytes.
Solitary cutaneous reticulohistiocytoma. In this example, most histiocytes are multinucleated. They have abundant eosinophilic cytoplasm, sometimes with fine vacuoles.

Q: The characteristic histiocytes in Reticulohistiocytosis express macrophage markers such as CD68 and [...], while lacking expression of S100, CD1a, and langerin.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The histiocytes are immunoreactive for CD163.
Solitary cutaneous reticulohistiocytoma. The histiocytes are negative for S100.
A: CD163
Back Extra: Reticulohistiocytosis
- Clinical: Reticulohistiocytosis can present as a solitary cutaneous lesion (reticulohistiocytoma) or as multiple lesions (multicentric reticulohistiocytosis), often associated with erosive polyarthritis.
- Micro: Histologically, reticulohistiocytosis is characterized by a dermal infiltrate of large mononuclear, binucleated, or multinucleated giant cells with randomly oriented nuclei and finely granular ground-glass cytoplasm.
- Ancillary: The histiocytes in reticulohistiocytosis are positive for CD14, CD68 (KP1 and PGM1), CD163, and vimentin, and negative for CD1a and CD207 (langerin).
Reference Gallery:
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). A single papular-nodular erythematous cutaneous lesion.
Multicentric reticulohistiocytosis. Multiple papular lesions over the hand joints.
Multicentric reticulohistiocytosis. Dermal infiltrate made of multinuclear ground-glass histiocytes.
Solitary reticulohistiocytoma. Upper dermal infiltrate made of mononucleate to multinucleate histiocytes with eosinophilic ground-glass cytoplasm.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). Tumour cells express CD68R/PGM1.
Diffuse reticulohistiocytosis. At higher magnification, the infiltrate is made of large to giant epithelioid cells with single or multiple randomly oriented nuclei and abundant eosinophilic “ground-glass” cytoplasm. Rare figures of emperipolesis may be seen.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The dome-shaped skin lesion comprises a dense infiltrate of large histiocytes in the dermis.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The histiocytes are very large and show prominent nucleoli and abundant hyaline cytoplasm.
Solitary cutaneous reticulohistiocytosis (reticulohistiocytoma). The histiocytes are immunoreactive for CD163.
Solitary cutaneous reticulohistiocytoma. The histiocytes are negative for S100.
Solitary cutaneous reticulohistiocytoma. A dome-shaped skin lesion formed by a dense dermal infiltrate of large histiocytes.
Solitary cutaneous reticulohistiocytoma. In this example, most histiocytes are multinucleated. They have abundant eosinophilic cytoplasm, sometimes with fine vacuoles.

Q: Clinically, Mycosis Fungoides typically presents as indolent, persisting patches and plaques that can eventually progress to tumors, nodules, or generalized diffuse erythema known as [...].
Mycosis fungoides. Stage IB: disseminated patches and thin plaques on the trunk.
Mycosis fungoides. Stage III: erythroderma.
A: erythroderma
Back Extra: Mycosis Fungoides
- Clinical: Mycosis fungoides typically presents as indolent, persisting patches and plaques that can eventually progress to nodules or erythroderma.
- Micro: Histopathologically, mycosis fungoides is characterized by small to medium-sized atypical lymphocytes with hyperconvoluted (cerebriform) nuclei, often forming Pautrier microabscesses.
- Ancillary: Immunophenotyping shows a CD2+, CD3+, TCRβ+, CD5+, CD4+, CD8− phenotype, with frequent loss of CD7 in advanced disease.
Reference Gallery:
Mycosis fungoides. Stage IA: poikilodermatous patch of the breast.
Mycosis fungoides. Stage IA: patches localized in the “bathing trunk” area.
Mycosis fungoides. Infiltrating cells can show cerebriform nuclei.
Mycosis fungoides. Stage IIB: plaque on the neck.
Mycosis fungoides. Stage IB: disseminated patches and thin plaques on the trunk.
Mycosis fungoides. Stage III: erythroderma.
Mycosis fungoides, large cell transformation, nodule, arm. Mycosis fungoides with large cell transformation and erythroderma. Numerous skin nodules amenable to sampling by FNA are present.
Patch/plaque mycosis fungoides, patch lesion. Small atypical lymphocytes migrate into lower to middle layers of the epidermis and are present in superficial papillary dermis.
Patch/plaque mycosis fungoides, patch lesion. TCRαβ heterodimer labels membranes of atypical epidermotropic lymphocytes with weak cytoplasmic presence, spotlighting cerebriform nuclei.
Mycosis fungoides, large cell transformation. FNAB skin nodule, MGG stain. Smears show large pleomorphic cells with convoluted nuclei.
Folliculotropic mycosis fungoides, early, with follicular mucin. Small to medium-sized atypical lymphocytes, epitheliotropic to follicular epithelium, and sebaceous gland structures. Mucin pools are present.
Mycosis fungoides, plaque lesion. Medium-sized atypical lymphocytes with Pautrier microabscess and a diffuse band-like involvement of the papillary dermis.

Q: Histologically, Mycosis Fungoides is characterized by small to medium-sized atypical lymphocytes that migrate into the epidermis and often aggregate to form characteristic [...].
Patch/plaque mycosis fungoides, patch lesion. Small atypical lymphocytes migrate into lower to middle layers of the epidermis and are present in superficial papillary dermis.
Mycosis fungoides, plaque lesion. Medium-sized atypical lymphocytes with Pautrier microabscess and a diffuse band-like involvement of the papillary dermis.
A: Pautrier microabscesses
Back Extra: Mycosis Fungoides
- Clinical: Mycosis fungoides typically presents as indolent, persisting patches and plaques that can eventually progress to nodules or erythroderma.
- Micro: Histopathologically, mycosis fungoides is characterized by small to medium-sized atypical lymphocytes with hyperconvoluted (cerebriform) nuclei, often forming Pautrier microabscesses.
- Ancillary: Immunophenotyping shows a CD2+, CD3+, TCRβ+, CD5+, CD4+, CD8− phenotype, with frequent loss of CD7 in advanced disease.
Reference Gallery:
Mycosis fungoides. Stage IA: poikilodermatous patch of the breast.
Mycosis fungoides. Stage IA: patches localized in the “bathing trunk” area.
Mycosis fungoides. Infiltrating cells can show cerebriform nuclei.
Mycosis fungoides. Stage IIB: plaque on the neck.
Mycosis fungoides. Stage IB: disseminated patches and thin plaques on the trunk.
Mycosis fungoides. Stage III: erythroderma.
Mycosis fungoides, large cell transformation, nodule, arm. Mycosis fungoides with large cell transformation and erythroderma. Numerous skin nodules amenable to sampling by FNA are present.
Patch/plaque mycosis fungoides, patch lesion. Small atypical lymphocytes migrate into lower to middle layers of the epidermis and are present in superficial papillary dermis.
Patch/plaque mycosis fungoides, patch lesion. TCRαβ heterodimer labels membranes of atypical epidermotropic lymphocytes with weak cytoplasmic presence, spotlighting cerebriform nuclei.
Mycosis fungoides, large cell transformation. FNAB skin nodule, MGG stain. Smears show large pleomorphic cells with convoluted nuclei.
Folliculotropic mycosis fungoides, early, with follicular mucin. Small to medium-sized atypical lymphocytes, epitheliotropic to follicular epithelium, and sebaceous gland structures. Mucin pools are present.
Mycosis fungoides, plaque lesion. Medium-sized atypical lymphocytes with Pautrier microabscess and a diffuse band-like involvement of the papillary dermis.

Q: The epidermotropic atypical T-cells (usually CD4+) in Mycosis Fungoides display distinctive, hyperconvoluted nuclei that are described as [...].
Mycosis fungoides. Infiltrating cells can show cerebriform nuclei.
Patch/plaque mycosis fungoides, patch lesion. TCRαβ heterodimer labels membranes of atypical epidermotropic lymphocytes with weak cytoplasmic presence, spotlighting cerebriform nuclei.
A: cerebriform
Back Extra: Mycosis Fungoides
- Clinical: Mycosis fungoides typically presents as indolent, persisting patches and plaques that can eventually progress to nodules or erythroderma.
- Micro: Histopathologically, mycosis fungoides is characterized by small to medium-sized atypical lymphocytes with hyperconvoluted (cerebriform) nuclei, often forming Pautrier microabscesses.
- Ancillary: Immunophenotyping shows a CD2+, CD3+, TCRβ+, CD5+, CD4+, CD8− phenotype, with frequent loss of CD7 in advanced disease.
Reference Gallery:
Mycosis fungoides. Stage IA: poikilodermatous patch of the breast.
Mycosis fungoides. Stage IA: patches localized in the “bathing trunk” area.
Mycosis fungoides. Infiltrating cells can show cerebriform nuclei.
Mycosis fungoides. Stage IIB: plaque on the neck.
Mycosis fungoides. Stage IB: disseminated patches and thin plaques on the trunk.
Mycosis fungoides. Stage III: erythroderma.
Mycosis fungoides, large cell transformation, nodule, arm. Mycosis fungoides with large cell transformation and erythroderma. Numerous skin nodules amenable to sampling by FNA are present.
Patch/plaque mycosis fungoides, patch lesion. Small atypical lymphocytes migrate into lower to middle layers of the epidermis and are present in superficial papillary dermis.
Patch/plaque mycosis fungoides, patch lesion. TCRαβ heterodimer labels membranes of atypical epidermotropic lymphocytes with weak cytoplasmic presence, spotlighting cerebriform nuclei.
Mycosis fungoides, large cell transformation. FNAB skin nodule, MGG stain. Smears show large pleomorphic cells with convoluted nuclei.
Folliculotropic mycosis fungoides, early, with follicular mucin. Small to medium-sized atypical lymphocytes, epitheliotropic to follicular epithelium, and sebaceous gland structures. Mucin pools are present.
Mycosis fungoides, plaque lesion. Medium-sized atypical lymphocytes with Pautrier microabscess and a diffuse band-like involvement of the papillary dermis.

Q: A patient presenting with a large, solitary, polypoid skin tumor with a dermal infiltrate of large anaplastic lymphoid cells lacking epidermotropism is highly characteristic of [...].
Primary cutaneous anaplastic large cell lymphoma. Large polypoid tumour on the leg.
Primary cutaneous anaplastic large cell lymphoma. Nodular infiltrate in the dermis and subcutis. Absence of epidermotropism.
A: Primary Cutaneous Anaplastic Large Cell Lymphoma
Back Extra: Primary Cutaneous Anaplastic Large Cell Lymphoma
- Clinical: Most patients present with solitary or localized skin nodules or tumours, often with ulceration. Multifocal lesions are seen in about 20% of patients.
- Micro: The dermis is infiltrated by tumour cells with anaplastic morphology, with round / oval / irregularly shaped nuclei, prominent nucleoli, and abundant cytoplasm.
- Ancillary: CD30 is expressed by > 75% of tumour cells, and the neoplastic cells show variable loss of CD2, CD3, CD5, and CD7.
Reference Gallery:
Primary cutaneous anaplastic large cell lymphoma. Large polypoid tumour on the leg.
Primary cutaneous anaplastic large cell lymphoma. Nodular infiltrate in the dermis and subcutis. Absence of epidermotropism.
Primary cutaneous anaplastic large cell lymphoma. Confluent infiltrate of large anaplastic lymphoid cells.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD30 by the tumour cells, with membranous and Golgi pattern.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD3 by small reactive T cells. Lack of expression of CD3 by the tumour cells.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD4 by the tumour cells.

Q: In Primary Cutaneous Anaplastic Large Cell Lymphoma, the neoplastic cells characteristically demonstrate strong expression of [...] in >75% of the tumor cells, often with a distinct membranous and Golgi pattern.
Primary cutaneous anaplastic large cell lymphoma. Confluent infiltrate of large anaplastic lymphoid cells.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD30 by the tumour cells, with membranous and Golgi pattern.
A: CD30
Back Extra: Primary Cutaneous Anaplastic Large Cell Lymphoma
- Clinical: Most patients present with solitary or localized skin nodules or tumours, often with ulceration. Multifocal lesions are seen in about 20% of patients.
- Micro: The dermis is infiltrated by tumour cells with anaplastic morphology, with round / oval / irregularly shaped nuclei, prominent nucleoli, and abundant cytoplasm.
- Ancillary: CD30 is expressed by > 75% of tumour cells, and the neoplastic cells show variable loss of CD2, CD3, CD5, and CD7.
Reference Gallery:
Primary cutaneous anaplastic large cell lymphoma. Large polypoid tumour on the leg.
Primary cutaneous anaplastic large cell lymphoma. Nodular infiltrate in the dermis and subcutis. Absence of epidermotropism.
Primary cutaneous anaplastic large cell lymphoma. Confluent infiltrate of large anaplastic lymphoid cells.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD30 by the tumour cells, with membranous and Golgi pattern.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD3 by small reactive T cells. Lack of expression of CD3 by the tumour cells.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD4 by the tumour cells.

Q: Immunohistochemistry in Primary Cutaneous Anaplastic Large Cell Lymphoma often demonstrates variable loss of pan-T-cell markers such as [...] by the tumor cells, while retaining CD4 expression.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD3 by small reactive T cells. Lack of expression of CD3 by the tumour cells.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD4 by the tumour cells.
A: CD3
Back Extra: Primary Cutaneous Anaplastic Large Cell Lymphoma
- Clinical: Most patients present with solitary or localized skin nodules or tumours, often with ulceration. Multifocal lesions are seen in about 20% of patients.
- Micro: The dermis is infiltrated by tumour cells with anaplastic morphology, with round / oval / irregularly shaped nuclei, prominent nucleoli, and abundant cytoplasm.
- Ancillary: CD30 is expressed by > 75% of tumour cells, and the neoplastic cells show variable loss of CD2, CD3, CD5, and CD7.
Reference Gallery:
Primary cutaneous anaplastic large cell lymphoma. Large polypoid tumour on the leg.
Primary cutaneous anaplastic large cell lymphoma. Nodular infiltrate in the dermis and subcutis. Absence of epidermotropism.
Primary cutaneous anaplastic large cell lymphoma. Confluent infiltrate of large anaplastic lymphoid cells.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD30 by the tumour cells, with membranous and Golgi pattern.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD3 by small reactive T cells. Lack of expression of CD3 by the tumour cells.
Primary cutaneous anaplastic large cell lymphoma. Expression of CD4 by the tumour cells.

Q: A highly characteristic immunohistochemical finding in Primary Cutaneous Acral CD8-Positive T-Cell Lymphoproliferative Disorder is a unique Golgi dot-like staining pattern for [...].
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Characteristic dot-like staining for CD68 (brown) in tumour cells (red) (immunohistochemistry, APAAP, double stain).
A: CD68
Back Extra: Primary Cutaneous Acral CD8-Positive T-Cell Lymphoproliferative Disorder
- Clinical: The tumour usually manifests as an asymptomatic, solitary, reddish, non-ulcerated papule, nodule, or (less frequently) plaque, measuring up to 40 mm, that grows slowly over weeks or months.
- Micro: The tumour is composed of a dense and monotonous dermal proliferation of atypical medium-sized lymphocytes with irregular and frequently folded nuclei with fine chromatin and moderate nuclear pleomorphism.
- Ancillary: CD3+, CD4−, CD8+, CD30−, βF1+, TIA1+ (granzyme B and perforin usually negative), and CD68 displays a characteristic Golgi dot-like staining pattern in the majority (> 80%) of cases.
Reference Gallery:
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Dense dermal monotonous infiltrate separated from the overlying epidermis by a grenz zone.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Medium-sized tumour cells with moderate nuclear atypia, fine chromatin, and small nucleoli.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Expression of CD8 by tumour cells.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Focal loss of CD5 expression by tumour cells.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Expression of TIA1 by tumour cells.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Characteristic dot-like staining for CD68 (brown) in tumour cells (red) (immunohistochemistry, APAAP, double stain).
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Erythematous tumour of the left helix.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. A reddish nodule on the lower leg.

Q: Histologically, Primary Cutaneous Acral CD8-Positive T-Cell Lymphoproliferative Disorder features a dense, monotonous dermal proliferation of atypical medium-sized lymphocytes separated from the epidermis by an uninvolved band of tissue known as a [...].
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Dense dermal monotonous infiltrate separated from the overlying epidermis by a grenz zone.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Medium-sized tumour cells with moderate nuclear atypia, fine chromatin, and small nucleoli.
A: grenz zone
Back Extra: Primary Cutaneous Acral CD8-Positive T-Cell Lymphoproliferative Disorder
- Clinical: The tumour usually manifests as an asymptomatic, solitary, reddish, non-ulcerated papule, nodule, or (less frequently) plaque, measuring up to 40 mm, that grows slowly over weeks or months.
- Micro: The tumour is composed of a dense and monotonous dermal proliferation of atypical medium-sized lymphocytes with irregular and frequently folded nuclei with fine chromatin and moderate nuclear pleomorphism.
- Ancillary: CD3+, CD4−, CD8+, CD30−, βF1+, TIA1+ (granzyme B and perforin usually negative), and CD68 displays a characteristic Golgi dot-like staining pattern in the majority (> 80%) of cases.
Reference Gallery:
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Dense dermal monotonous infiltrate separated from the overlying epidermis by a grenz zone.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Medium-sized tumour cells with moderate nuclear atypia, fine chromatin, and small nucleoli.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Expression of CD8 by tumour cells.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Focal loss of CD5 expression by tumour cells.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Expression of TIA1 by tumour cells.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Characteristic dot-like staining for CD68 (brown) in tumour cells (red) (immunohistochemistry, APAAP, double stain).
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. Erythematous tumour of the left helix.
Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder. A reddish nodule on the lower leg.

Q: A solitary erythematous nodule showing a dense dermal infiltrate of small to medium pleomorphic CD4+ T cells with a low Ki-67 index (~5-10%) is characteristic of [...].
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. Typical presentation as a solitary erythematous lesion on the forehead.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The lymphoid cells are small to intermediate in size, with mild pleomorphism. Admixed histiocytes can be seen.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The atypical T cells are positive for CD4.
A: Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder
Back Extra: Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder
- Clinical: Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder commonly presents as a solitary erythematous nodule, followed by tumour, papule, macule, or plaque.
- Micro: The lesion consists of a dense, diffuse to nodular infiltrate within the dermis, often extending into the subcutis. Small to medium-sized pleomorphic T cells predominate, with occasional large cells.
- Ancillary: Immunophenotyping shows CD3+, CD4+, CD8−, and CD30− cells, with an admixed B-cell component and a low Ki-67 proliferation index (~5-10%).
Reference Gallery:
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. Typical presentation as a solitary erythematous lesion on the forehead.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The lesion consists of a dense, diffuse to nodular infiltrate within the dermis, with a tendency to infiltrate the subcutis.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The lymphoid cells are small to intermediate in size, with mild pleomorphism. Admixed histiocytes can be seen.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The atypical T cells are positive for CD4.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The Ki-67 proliferation index is relatively low (~5–10%).

Q: Clinically, Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder most commonly presents as a solitary erythematous [...], though it can also manifest as a tumor, papule, macule, or plaque.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. Typical presentation as a solitary erythematous lesion on the forehead.
A: nodule
Back Extra: Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder
- Clinical: Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder commonly presents as a solitary erythematous nodule, followed by tumour, papule, macule, or plaque.
- Micro: The lesion consists of a dense, diffuse to nodular infiltrate within the dermis, often extending into the subcutis. Small to medium-sized pleomorphic T cells predominate, with occasional large cells.
- Ancillary: Immunophenotyping shows CD3+, CD4+, CD8−, and CD30− cells, with an admixed B-cell component and a low Ki-67 proliferation index (~5-10%).
Reference Gallery:
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. Typical presentation as a solitary erythematous lesion on the forehead.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The lesion consists of a dense, diffuse to nodular infiltrate within the dermis, with a tendency to infiltrate the subcutis.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The lymphoid cells are small to intermediate in size, with mild pleomorphism. Admixed histiocytes can be seen.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The atypical T cells are positive for CD4.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The Ki-67 proliferation index is relatively low (~5–10%).

Q: In Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder, the atypical dermal infiltrate characteristically demonstrates a(n) [...] Ki-67 proliferation index (approximately 5-10%), which helps distinguish it from more aggressive lymphomas.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The Ki-67 proliferation index is relatively low (~5–10%).
A: low
Back Extra: Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder
- Clinical: Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder commonly presents as a solitary erythematous nodule, followed by tumour, papule, macule, or plaque.
- Micro: The lesion consists of a dense, diffuse to nodular infiltrate within the dermis, often extending into the subcutis. Small to medium-sized pleomorphic T cells predominate, with occasional large cells.
- Ancillary: Immunophenotyping shows CD3+, CD4+, CD8−, and CD30− cells, with an admixed B-cell component and a low Ki-67 proliferation index (~5-10%).
Reference Gallery:
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. Typical presentation as a solitary erythematous lesion on the forehead.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The lesion consists of a dense, diffuse to nodular infiltrate within the dermis, with a tendency to infiltrate the subcutis.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The lymphoid cells are small to intermediate in size, with mild pleomorphism. Admixed histiocytes can be seen.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The atypical T cells are positive for CD4.
Primary cutaneous CD4-positive small or medium T-cell lymphoproliferative disorder. The Ki-67 proliferation index is relatively low (~5–10%).

Q: A patient presents with firm, erythematous to violaceous plaques and tumors primarily located on the head, neck, and trunk. Biopsy reveals a cutaneous B-cell infiltrate composed of monotonous cells that are positive for BCL6 but characteristically negative for BCL2. This presentation is highly suggestive of [...].
Primary cutaneous follicle centre lymphoma. Confluent tumours on the scalp.
Primary cutaneous follicle centre lymphoma. Multiple coalescing plaques and tumours of the back.
A: Primary Cutaneous Follicle Centre Lymphoma
Back Extra: Primary Cutaneous Follicle Centre Lymphoma
- Clinical: Patients typically present with firm, erythematous to violaceous plaques, nodules, or tumours on the head/neck or trunk.
- Micro: Histologically, the infiltrates show a follicular, follicular and diffuse, or diffuse growth pattern with a monotonous proliferation of BCL6-positive follicle centre cells.
- Ancillary: Consistent expression of BCL6, and positive for CD20 and CD79a, but usually negative for BCL2 and IRF4 (MUM1).
Reference Gallery:
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Cutaneous involvement by a nodular and in part diffuse lymphoid infiltrate extending into the subcutis.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. The lymphoma shows a confluent nodular and vaguely follicular architecture.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Sheets of large and in part spindle cells with intermingled centrocytoid cells and some polylobated cells are seen.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Strong expression of BCL6 within the tumour cells.
Primary cutaneous follicle centre lymphoma. There is only faint expression of BCL2 within the neoplastic cells.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Ki-67 immunohistochemistry shows a high proliferative index.
Primary cutaneous follicle centre lymphoma. Plaques and tumours on the back.
Primary cutaneous follicle centre lymphoma. Confluent tumours on the scalp.
Primary cutaneous follicle centre lymphoma. Multiple coalescing plaques and tumours of the back.
Primary cutaneous follicle centre lymphoma. Multiple coalescing plaques and tumours of the back after radiotherapy.
Primary cutaneous follicle centre lymphoma. Irregular and disrupted networks of CD21-positive follicular dendritic cells within the tumoural infiltrates.

Q: The neoplastic cells in Primary Cutaneous Follicle Centre Lymphoma consistently express pan-B cell markers and BCL6, but characteristically lack strong expression of [...], a feature that helps distinguish it from secondary cutaneous involvement by systemic follicular lymphoma.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Strong expression of BCL6 within the tumour cells.
Primary cutaneous follicle centre lymphoma. There is only faint expression of BCL2 within the neoplastic cells.
A: BCL2
Back Extra: Primary Cutaneous Follicle Centre Lymphoma
- Clinical: Patients typically present with firm, erythematous to violaceous plaques, nodules, or tumours on the head/neck or trunk.
- Micro: Histologically, the infiltrates show a follicular, follicular and diffuse, or diffuse growth pattern with a monotonous proliferation of BCL6-positive follicle centre cells.
- Ancillary: Consistent expression of BCL6, and positive for CD20 and CD79a, but usually negative for BCL2 and IRF4 (MUM1).
Reference Gallery:
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Cutaneous involvement by a nodular and in part diffuse lymphoid infiltrate extending into the subcutis.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. The lymphoma shows a confluent nodular and vaguely follicular architecture.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Sheets of large and in part spindle cells with intermingled centrocytoid cells and some polylobated cells are seen.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Strong expression of BCL6 within the tumour cells.
Primary cutaneous follicle centre lymphoma. There is only faint expression of BCL2 within the neoplastic cells.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Ki-67 immunohistochemistry shows a high proliferative index.
Primary cutaneous follicle centre lymphoma. Plaques and tumours on the back.
Primary cutaneous follicle centre lymphoma. Confluent tumours on the scalp.
Primary cutaneous follicle centre lymphoma. Multiple coalescing plaques and tumours of the back.
Primary cutaneous follicle centre lymphoma. Multiple coalescing plaques and tumours of the back after radiotherapy.
Primary cutaneous follicle centre lymphoma. Irregular and disrupted networks of CD21-positive follicular dendritic cells within the tumoural infiltrates.

Q: In Primary Cutaneous Follicle Centre Lymphoma, the tumor infiltrates often contain irregular and disrupted networks of [...], which can be specifically highlighted by CD21 immunohistochemistry.
Primary cutaneous follicle centre lymphoma. Irregular and disrupted networks of CD21-positive follicular dendritic cells within the tumoural infiltrates.
A: follicular dendritic cells
Back Extra: Primary Cutaneous Follicle Centre Lymphoma
- Clinical: Patients typically present with firm, erythematous to violaceous plaques, nodules, or tumours on the head/neck or trunk.
- Micro: Histologically, the infiltrates show a follicular, follicular and diffuse, or diffuse growth pattern with a monotonous proliferation of BCL6-positive follicle centre cells.
- Ancillary: Consistent expression of BCL6, and positive for CD20 and CD79a, but usually negative for BCL2 and IRF4 (MUM1).
Reference Gallery:
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Cutaneous involvement by a nodular and in part diffuse lymphoid infiltrate extending into the subcutis.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. The lymphoma shows a confluent nodular and vaguely follicular architecture.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Sheets of large and in part spindle cells with intermingled centrocytoid cells and some polylobated cells are seen.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Strong expression of BCL6 within the tumour cells.
Primary cutaneous follicle centre lymphoma. There is only faint expression of BCL2 within the neoplastic cells.
Primary cutaneous follicle centre lymphoma with a predominance of large/spindled cells. Ki-67 immunohistochemistry shows a high proliferative index.
Primary cutaneous follicle centre lymphoma. Plaques and tumours on the back.
Primary cutaneous follicle centre lymphoma. Confluent tumours on the scalp.
Primary cutaneous follicle centre lymphoma. Multiple coalescing plaques and tumours of the back.
Primary cutaneous follicle centre lymphoma. Multiple coalescing plaques and tumours of the back after radiotherapy.
Primary cutaneous follicle centre lymphoma. Irregular and disrupted networks of CD21-positive follicular dendritic cells within the tumoural infiltrates.

Q: Histologically, Primary Cutaneous Marginal Zone Lymphoma is characterized by a dense, dermal multinodular infiltrate of small lymphocytes surrounding reactive germinal centers, often accompanied by aggregates of [...] at the periphery.
Primary cutaneous marginal zone B-cell lymphoma. Aggregates of plasma cells in the periphery of the infiltrates and superficial subepidermal component.
Primary cutaneous marginal zone lymphoma. Confluent nodular aggregates of lymphoid infiltrate in the dermis, with sparing of the epidermis.
Primary cutaneous marginal zone lymphoma. The neoplastic cells surround a reactive germinal centre and comprise small lymphoid cells slightly larger than small lymphocytes.
A: plasma cells
Back Extra: Primary Cutaneous Marginal Zone Lymphoma
- Clinical: Patients with Primary Cutaneous Marginal Zone Lymphoma (PCMZL) present with non-ulcerated multifocal and sometimes solitary red or violaceous plaques or nodules.
- Micro: PCMZL shows a dense dermal multinodular infiltrate of small lymphocytes, plasma cells, and follicles with reactive germinal centres.
- Ancillary: The neoplastic B cells in PCMZL are positive for BCL2 and negative for CD5, CD10, BCL6, and cyclin D1/SOX11.
Reference Gallery:
Primary cutaneous marginal zone lymphoma. Erythematous nodule on the upper lateral trunk.
Primary cutaneous marginal zone B-cell lymphoma. Nodular dermal infiltrate with extension into the superficial parts of the subcutaneous fat.
Primary cutaneous marginal zone B-cell lymphoma. Infiltrate of small lymphocytes and reactive germinal centres with tingible-body macrophages.
Primary cutaneous marginal zone B-cell lymphoma. Aggregates of plasma cells in the periphery of the infiltrates and superficial subepidermal component.
Primary cutaneous marginal zone B-cell lymphoma. Characteristic high number of T cells highlighted by the expression of CD3 in the class-switched form.
Primary cutaneous marginal zone B-cell lymphoma. Expression of BCL2 by tumour cells and T cells. Absence of BCL2 in the germinal centres.
Primary cutaneous marginal zone B-cell lymphoma. Expression of BCL6 in the germinal centres, but not by tumour cells.
Primary cutaneous marginal zone B-cell lymphoma. Monotypic expression of immunoglobulin light chain kappa.
Primary cutaneous marginal zone lymphoma. Confluent nodular aggregates of lymphoid infiltrate in the dermis, with sparing of the epidermis.
Primary cutaneous marginal zone lymphoma. The neoplastic cells surround a reactive germinal centre and comprise small lymphoid cells slightly larger than small lymphocytes.
Primary cutaneous marginal zone lymphoma. Reactive germinal centre is often identifiable.
Primary cutaneous marginal zone lymphoma. The neoplastic B cells are accompanied by large numbers of CD3+ reactive T cells.

Q: In Primary Cutaneous Marginal Zone Lymphoma, the neoplastic B cells surrounding the reactive germinal centers typically show positive expression for [...], while being negative for CD5, CD10, and BCL6.
Primary cutaneous marginal zone B-cell lymphoma. Expression of BCL2 by tumour cells and T cells. Absence of BCL2 in the germinal centres.
Primary cutaneous marginal zone B-cell lymphoma. Expression of BCL6 in the germinal centres, but not by tumour cells.
A: BCL2
Back Extra: Primary Cutaneous Marginal Zone Lymphoma
- Clinical: Patients with Primary Cutaneous Marginal Zone Lymphoma (PCMZL) present with non-ulcerated multifocal and sometimes solitary red or violaceous plaques or nodules.
- Micro: PCMZL shows a dense dermal multinodular infiltrate of small lymphocytes, plasma cells, and follicles with reactive germinal centres.
- Ancillary: The neoplastic B cells in PCMZL are positive for BCL2 and negative for CD5, CD10, BCL6, and cyclin D1/SOX11.
Reference Gallery:
Primary cutaneous marginal zone lymphoma. Erythematous nodule on the upper lateral trunk.
Primary cutaneous marginal zone B-cell lymphoma. Nodular dermal infiltrate with extension into the superficial parts of the subcutaneous fat.
Primary cutaneous marginal zone B-cell lymphoma. Infiltrate of small lymphocytes and reactive germinal centres with tingible-body macrophages.
Primary cutaneous marginal zone B-cell lymphoma. Aggregates of plasma cells in the periphery of the infiltrates and superficial subepidermal component.
Primary cutaneous marginal zone B-cell lymphoma. Characteristic high number of T cells highlighted by the expression of CD3 in the class-switched form.
Primary cutaneous marginal zone B-cell lymphoma. Expression of BCL2 by tumour cells and T cells. Absence of BCL2 in the germinal centres.
Primary cutaneous marginal zone B-cell lymphoma. Expression of BCL6 in the germinal centres, but not by tumour cells.
Primary cutaneous marginal zone B-cell lymphoma. Monotypic expression of immunoglobulin light chain kappa.
Primary cutaneous marginal zone lymphoma. Confluent nodular aggregates of lymphoid infiltrate in the dermis, with sparing of the epidermis.
Primary cutaneous marginal zone lymphoma. The neoplastic cells surround a reactive germinal centre and comprise small lymphoid cells slightly larger than small lymphocytes.
Primary cutaneous marginal zone lymphoma. Reactive germinal centre is often identifiable.
Primary cutaneous marginal zone lymphoma. The neoplastic B cells are accompanied by large numbers of CD3+ reactive T cells.

Q: A characteristic feature of Primary Cutaneous Marginal Zone Lymphoma is that the neoplastic B cells are accompanied by a high number of reactive T cells, which are highlighted by the immunostain [...].
Primary cutaneous marginal zone B-cell lymphoma. Characteristic high number of T cells highlighted by the expression of CD3 in the class-switched form.
Primary cutaneous marginal zone lymphoma. The neoplastic B cells are accompanied by large numbers of CD3+ reactive T cells.
A: CD3
Back Extra: Primary Cutaneous Marginal Zone Lymphoma
- Clinical: Patients with Primary Cutaneous Marginal Zone Lymphoma (PCMZL) present with non-ulcerated multifocal and sometimes solitary red or violaceous plaques or nodules.
- Micro: PCMZL shows a dense dermal multinodular infiltrate of small lymphocytes, plasma cells, and follicles with reactive germinal centres.
- Ancillary: The neoplastic B cells in PCMZL are positive for BCL2 and negative for CD5, CD10, BCL6, and cyclin D1/SOX11.
Reference Gallery:
Primary cutaneous marginal zone lymphoma. Erythematous nodule on the upper lateral trunk.
Primary cutaneous marginal zone B-cell lymphoma. Nodular dermal infiltrate with extension into the superficial parts of the subcutaneous fat.
Primary cutaneous marginal zone B-cell lymphoma. Infiltrate of small lymphocytes and reactive germinal centres with tingible-body macrophages.
Primary cutaneous marginal zone B-cell lymphoma. Aggregates of plasma cells in the periphery of the infiltrates and superficial subepidermal component.
Primary cutaneous marginal zone B-cell lymphoma. Characteristic high number of T cells highlighted by the expression of CD3 in the class-switched form.
Primary cutaneous marginal zone B-cell lymphoma. Expression of BCL2 by tumour cells and T cells. Absence of BCL2 in the germinal centres.
Primary cutaneous marginal zone B-cell lymphoma. Expression of BCL6 in the germinal centres, but not by tumour cells.
Primary cutaneous marginal zone B-cell lymphoma. Monotypic expression of immunoglobulin light chain kappa.
Primary cutaneous marginal zone lymphoma. Confluent nodular aggregates of lymphoid infiltrate in the dermis, with sparing of the epidermis.
Primary cutaneous marginal zone lymphoma. The neoplastic cells surround a reactive germinal centre and comprise small lymphoid cells slightly larger than small lymphocytes.
Primary cutaneous marginal zone lymphoma. Reactive germinal centre is often identifiable.
Primary cutaneous marginal zone lymphoma. The neoplastic B cells are accompanied by large numbers of CD3+ reactive T cells.

Q: Histologically, a diffuse or nodular dermal infiltrate of cohesive sheets of pleomorphic medium-to-large lymphocytes that typically spares the epidermis (limited epidermotropism) is highly characteristic of [...].
Primary cutaneous peripheral T-cell lymphoma NOS. Diffuse dermal infiltrate of cohesive sheets of lymphocytes with involvement of the subcutis. The epidermis is spared.
Primary cutaneous peripheral T-cell lymphoma NOS. Sheets of pleomorphic small, medium-sized, and large tumour cells.
A: Primary Cutaneous Peripheral T-Cell Lymphoma, Not Otherwise Specified
Back Extra: Primary Cutaneous Peripheral T-Cell Lymphoma, Not Otherwise Specified
- Clinical: Most patients present with disseminated plaques, papules, or tumours, and about one-third show (initially) solitary lesions. Ulceration can be found (~15%).
- Micro: There is a diffuse or nodular dermal infiltrate consisting of cohesive sheets of mostly medium-sized to large tumour cells, with subcutis involvement and limited epidermotropism in about one-third of cases.
- Ancillary: The tumour cells are positive for CD3 and CD2, with the most common phenotype being CD4+/CD8−. About one-third show a CD4−/CD8− phenotype, and approximately 10% are CD4+/CD8+.
Reference Gallery:
Primary cutaneous peripheral T-cell lymphoma NOS. Large red tumour on the left forearm.
Primary cutaneous peripheral T-cell lymphoma NOS. Diffuse dermal infiltrate of cohesive sheets of lymphocytes with involvement of the subcutis. The epidermis is spared.
Primary cutaneous peripheral T-cell lymphoma NOS. Sheets of pleomorphic small, medium-sized, and large tumour cells.
Primary cutaneous peripheral T-cell lymphoma NOS. The tumour cells are positive for CD3.
Primary cutaneous peripheral T-cell lymphoma NOS. The tumour cells show a partial loss of CD4.
Primary cutaneous peripheral T-cell lymphoma NOS. Partial loss of CD4.
Primary cutaneous peripheral T-cell lymphoma NOS. The tumour cells are negative for CD8.

Q: Presenting clinically as disseminated plaques or red tumors, [...] most commonly demonstrates a CD3+, CD4+/CD8- immunophenotype, though aberrant loss of T-cell antigens can occur.
Primary cutaneous peripheral T-cell lymphoma NOS. Large red tumour on the left forearm.
Primary cutaneous peripheral T-cell lymphoma NOS. The tumour cells are positive for CD3.
Primary cutaneous peripheral T-cell lymphoma NOS. The tumour cells are negative for CD8.
A: Primary Cutaneous Peripheral T-Cell Lymphoma, Not Otherwise Specified
Back Extra: Primary Cutaneous Peripheral T-Cell Lymphoma, Not Otherwise Specified
- Clinical: Most patients present with disseminated plaques, papules, or tumours, and about one-third show (initially) solitary lesions. Ulceration can be found (~15%).
- Micro: There is a diffuse or nodular dermal infiltrate consisting of cohesive sheets of mostly medium-sized to large tumour cells, with subcutis involvement and limited epidermotropism in about one-third of cases.
- Ancillary: The tumour cells are positive for CD3 and CD2, with the most common phenotype being CD4+/CD8−. About one-third show a CD4−/CD8− phenotype, and approximately 10% are CD4+/CD8+.
Reference Gallery:
Primary cutaneous peripheral T-cell lymphoma NOS. Large red tumour on the left forearm.
Primary cutaneous peripheral T-cell lymphoma NOS. Diffuse dermal infiltrate of cohesive sheets of lymphocytes with involvement of the subcutis. The epidermis is spared.
Primary cutaneous peripheral T-cell lymphoma NOS. Sheets of pleomorphic small, medium-sized, and large tumour cells.
Primary cutaneous peripheral T-cell lymphoma NOS. The tumour cells are positive for CD3.
Primary cutaneous peripheral T-cell lymphoma NOS. The tumour cells show a partial loss of CD4.
Primary cutaneous peripheral T-cell lymphoma NOS. Partial loss of CD4.
Primary cutaneous peripheral T-cell lymphoma NOS. The tumour cells are negative for CD8.

Q: Histologically, Reactive B-cell-rich lymphoid proliferation (rB-LP) features a dense dermal infiltrate predominantly composed of B cells that frequently form prominent reactive [...].
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Diffuse dermal lymphocytic infiltrate predominantly composed of B cells.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Large germinal centres with small mantle zones.
A: germinal centers
Back Extra: Reactive B-cell-rich lymphoid proliferation (rB-LP)
- Clinical: rB-LP often presents as solitary red, brown, or bluish nodules, typically on the head, neck, upper extremities, and trunk. The miliarial subtype is characterized by multiple small semitranslucent papules in sunlight-exposed areas.
- Micro: Histologically, rB-LP is marked by a nodular or diffuse dermal lymphocytic infiltrate predominantly composed of B cells, with admixed T lymphocytes, plasma cells, and eosinophils. Reactive germinal centres are common.
- Ancillary: Immunohistochemistry shows B cells positive for CD20, CD79a, and PAX5, with reactive germinal centres positive for CD10 and BCL6 but negative for BCL2. Polyclonal B-cell infiltrates and the absence of clonality are key distinguishing factors.
Reference Gallery:
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Red plaques on the scrotum.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Diffuse dermal lymphocytic infiltrate predominantly composed of B cells.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Large germinal centres with small mantle zones.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The infiltrate consists predominantly of CD79a-positive B cells.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The reactive germinal centres are positive for BCL6.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The reactive germinal centres are negative for BCL2. The small mantle zones are highlighted.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The proliferative activity outlined by Ki-67 is high and relatively well limited to the reactive germinal centres.

Q: A key immunohistochemical feature of Reactive B-cell-rich lymphoid proliferation (rB-LP) is that the reactive germinal centers are characteristically negative for [...], which helps distinguish it from neoplastic processes.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The reactive germinal centres are negative for BCL2. The small mantle zones are highlighted.
A: BCL2
Back Extra: Reactive B-cell-rich lymphoid proliferation (rB-LP)
- Clinical: rB-LP often presents as solitary red, brown, or bluish nodules, typically on the head, neck, upper extremities, and trunk. The miliarial subtype is characterized by multiple small semitranslucent papules in sunlight-exposed areas.
- Micro: Histologically, rB-LP is marked by a nodular or diffuse dermal lymphocytic infiltrate predominantly composed of B cells, with admixed T lymphocytes, plasma cells, and eosinophils. Reactive germinal centres are common.
- Ancillary: Immunohistochemistry shows B cells positive for CD20, CD79a, and PAX5, with reactive germinal centres positive for CD10 and BCL6 but negative for BCL2. Polyclonal B-cell infiltrates and the absence of clonality are key distinguishing factors.
Reference Gallery:
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Red plaques on the scrotum.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Diffuse dermal lymphocytic infiltrate predominantly composed of B cells.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Large germinal centres with small mantle zones.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The infiltrate consists predominantly of CD79a-positive B cells.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The reactive germinal centres are positive for BCL6.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The reactive germinal centres are negative for BCL2. The small mantle zones are highlighted.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The proliferative activity outlined by Ki-67 is high and relatively well limited to the reactive germinal centres.

Q: In Reactive B-cell-rich lymphoid proliferation (rB-LP), the proliferative index is typically high and well-limited to the reactive germinal centers, as highlighted by the [...] stain.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The proliferative activity outlined by Ki-67 is high and relatively well limited to the reactive germinal centres.
A: Ki-67
Back Extra: Reactive B-cell-rich lymphoid proliferation (rB-LP)
- Clinical: rB-LP often presents as solitary red, brown, or bluish nodules, typically on the head, neck, upper extremities, and trunk. The miliarial subtype is characterized by multiple small semitranslucent papules in sunlight-exposed areas.
- Micro: Histologically, rB-LP is marked by a nodular or diffuse dermal lymphocytic infiltrate predominantly composed of B cells, with admixed T lymphocytes, plasma cells, and eosinophils. Reactive germinal centres are common.
- Ancillary: Immunohistochemistry shows B cells positive for CD20, CD79a, and PAX5, with reactive germinal centres positive for CD10 and BCL6 but negative for BCL2. Polyclonal B-cell infiltrates and the absence of clonality are key distinguishing factors.
Reference Gallery:
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Red plaques on the scrotum.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Diffuse dermal lymphocytic infiltrate predominantly composed of B cells.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. Large germinal centres with small mantle zones.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The infiltrate consists predominantly of CD79a-positive B cells.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The reactive germinal centres are positive for BCL6.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The reactive germinal centres are negative for BCL2. The small mantle zones are highlighted.
Borrelia-associated reactive B-cell–rich lymphoid proliferation. The proliferative activity outlined by Ki-67 is high and relatively well limited to the reactive germinal centres.

Q: Histologically, Reactive T-cell–rich lymphoid proliferations characteristically feature a dense dermal infiltrate of small lymphocytes with prominent [...].
Reactive T-cell–rich lymphoid proliferations. Dense dermal lymphocytic infiltrates with perifollicular accentuation.
Reactive T-cell–rich lymphoid proliferations. Nodular reactive T-cell–rich lymphoid proliferation: dermal nodular infiltrate composed mostly of small lymphocytes.
Reactive T-cell–rich lymphoid proliferations. Infiltrate of small lymphocytes without nuclear atypia.
A: perifollicular accentuation
Back Extra: Reactive T-cell–rich lymphoid proliferations
- Clinical: Reactive T-cell–rich lymphoid proliferations (rT-LPs) can manifest as solitary reddish nodules, papules, maculopapular eruptions, or erythroderma, often mimicking cutaneous T-cell lymphomas.
- Micro: Histologically, rT-LPs are characterized by a nodular or diffuse dermal infiltrate of small lymphocytes, often with perifollicular accentuation and a lack of significant nuclear atypia.
- Ancillary: Immunohistochemistry shows CD3-positive T cells, with CD4-positive cells dominating in the dermis and CD8-positive cells in the epidermis. CD30 can be expressed by scattered atypical lymphocytes.
Reference Gallery:
Reactive T-cell–rich lymphoid proliferations. Erythematous nodule on the nose.
Reactive T-cell–rich lymphoid proliferations. Dense dermal lymphocytic infiltrates with perifollicular accentuation.
Reactive T-cell–rich lymphoid proliferations. Dominant T-cell component with expression of CD3 by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. B-cell component with expression of CD20 by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Nodular reactive T-cell–rich lymphoid proliferation: dermal nodular infiltrate composed mostly of small lymphocytes.
Reactive T-cell–rich lymphoid proliferations. Infiltrate of small lymphocytes without nuclear atypia.
Reactive T-cell–rich lymphoid proliferations. Expression of CD4 by the majority of T cells by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with exocytosis of atypically appearing small lymphocytes into the basal layer of the epidermis. Presence of eosinophils in the dermal infiltrate (often seen in drug reaction).
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with exocytosis of numerous CD3-positive T cells, with lining-up along junctional zone by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with scattered CD8-positive lymphocytes.
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with expression of CD4 by lymphocytes located in the dermis and epidermis.
Reactive T-cell–rich lymphoid proliferations. CD30-positive reactive T-cell–rich lymphoid proliferation: molluscum contagiosum with atypical lymphocytic infiltrate.

Q: In Reactive T-cell–rich lymphoid proliferations, immunohistochemistry demonstrates a dominant T-cell component where [...]-positive cells typically predominate in the dermal infiltrate.
Reactive T-cell–rich lymphoid proliferations. Dominant T-cell component with expression of CD3 by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Expression of CD4 by the majority of T cells by immunohistochemistry.
A: CD4
Back Extra: Reactive T-cell–rich lymphoid proliferations
- Clinical: Reactive T-cell–rich lymphoid proliferations (rT-LPs) can manifest as solitary reddish nodules, papules, maculopapular eruptions, or erythroderma, often mimicking cutaneous T-cell lymphomas.
- Micro: Histologically, rT-LPs are characterized by a nodular or diffuse dermal infiltrate of small lymphocytes, often with perifollicular accentuation and a lack of significant nuclear atypia.
- Ancillary: Immunohistochemistry shows CD3-positive T cells, with CD4-positive cells dominating in the dermis and CD8-positive cells in the epidermis. CD30 can be expressed by scattered atypical lymphocytes.
Reference Gallery:
Reactive T-cell–rich lymphoid proliferations. Erythematous nodule on the nose.
Reactive T-cell–rich lymphoid proliferations. Dense dermal lymphocytic infiltrates with perifollicular accentuation.
Reactive T-cell–rich lymphoid proliferations. Dominant T-cell component with expression of CD3 by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. B-cell component with expression of CD20 by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Nodular reactive T-cell–rich lymphoid proliferation: dermal nodular infiltrate composed mostly of small lymphocytes.
Reactive T-cell–rich lymphoid proliferations. Infiltrate of small lymphocytes without nuclear atypia.
Reactive T-cell–rich lymphoid proliferations. Expression of CD4 by the majority of T cells by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with exocytosis of atypically appearing small lymphocytes into the basal layer of the epidermis. Presence of eosinophils in the dermal infiltrate (often seen in drug reaction).
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with exocytosis of numerous CD3-positive T cells, with lining-up along junctional zone by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with scattered CD8-positive lymphocytes.
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with expression of CD4 by lymphocytes located in the dermis and epidermis.
Reactive T-cell–rich lymphoid proliferations. CD30-positive reactive T-cell–rich lymphoid proliferation: molluscum contagiosum with atypical lymphocytic infiltrate.

Q: Mycosis fungoides–like Reactive T-cell–rich lymphoid proliferations are often caused by drug reactions and feature exocytosis of lymphocytes into the basal epidermis accompanied by dermal [...].
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with exocytosis of atypically appearing small lymphocytes into the basal layer of the epidermis. Presence of eosinophils in the dermal infiltrate (often seen in drug reaction).
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with exocytosis of numerous CD3-positive T cells, with lining-up along junctional zone by immunohistochemistry.
A: eosinophils
Back Extra: Reactive T-cell–rich lymphoid proliferations
- Clinical: Reactive T-cell–rich lymphoid proliferations (rT-LPs) can manifest as solitary reddish nodules, papules, maculopapular eruptions, or erythroderma, often mimicking cutaneous T-cell lymphomas.
- Micro: Histologically, rT-LPs are characterized by a nodular or diffuse dermal infiltrate of small lymphocytes, often with perifollicular accentuation and a lack of significant nuclear atypia.
- Ancillary: Immunohistochemistry shows CD3-positive T cells, with CD4-positive cells dominating in the dermis and CD8-positive cells in the epidermis. CD30 can be expressed by scattered atypical lymphocytes.
Reference Gallery:
Reactive T-cell–rich lymphoid proliferations. Erythematous nodule on the nose.
Reactive T-cell–rich lymphoid proliferations. Dense dermal lymphocytic infiltrates with perifollicular accentuation.
Reactive T-cell–rich lymphoid proliferations. Dominant T-cell component with expression of CD3 by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. B-cell component with expression of CD20 by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Nodular reactive T-cell–rich lymphoid proliferation: dermal nodular infiltrate composed mostly of small lymphocytes.
Reactive T-cell–rich lymphoid proliferations. Infiltrate of small lymphocytes without nuclear atypia.
Reactive T-cell–rich lymphoid proliferations. Expression of CD4 by the majority of T cells by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with exocytosis of atypically appearing small lymphocytes into the basal layer of the epidermis. Presence of eosinophils in the dermal infiltrate (often seen in drug reaction).
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with exocytosis of numerous CD3-positive T cells, with lining-up along junctional zone by immunohistochemistry.
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with scattered CD8-positive lymphocytes.
Reactive T-cell–rich lymphoid proliferations. Mycosis fungoides–like reactive T-cell–rich lymphoid proliferation: drug reaction with expression of CD4 by lymphocytes located in the dermis and epidermis.
Reactive T-cell–rich lymphoid proliferations. CD30-positive reactive T-cell–rich lymphoid proliferation: molluscum contagiosum with atypical lymphocytic infiltrate.

Q: A classic morphologic feature of Rosai-Dorfman Disease is the presence of intact hematopoietic cells (often lymphocytes or plasma cells) within the cytoplasm of large histiocytes, a phenomenon known as [...].
Cutaneous Rosai–Dorfman disease. Accumulation of large histiocytes with characteristic emperipolesis.
Cutaneous Rosai–Dorfman disease. The distinctive histiocytes of Rosai–Dorfman disease are very large, with pale-staining cytoplasm, round nuclei, and large nucleoli. Plasma cells are found in the cytoplasm of the histiocytes (emperipolesis).
A: emperipolesis
Back Extra: Rosai-Dorfman Disease
- Clinical: Multiple painless reddish-brown papules, nodules, or plaques are typical, with involvement of the trunk, head, and neck. Cutaneous RDD often resolves spontaneously, but extranodal disease may require surgical intervention if vital structures are compromised.
- Micro: Histologically, cutaneous RDD shows large histiocytes with pale-staining cytoplasm, round nuclei, and prominent nucleoli. Emperipolesis, the presence of intact hematopoietic cells within the histiocyte cytoplasm, is characteristic.
- Ancillary: Immunohistochemically, RDD histiocytes are S100-positive and often positive for OCT2, cyclin D1, and phosphorylated ERK. They lack CD1a and CD207 (langerin). Gain-of-function mutations in the MAPK/ERK pathway are common.
Reference Gallery:
Cutaneous Rosai–Dorfman disease. Nodular proliferation of enlarged histiocytes associated with plasma cells and fibrosis, occupying the dermis and subcutaneous tissue.
Cutaneous Rosai–Dorfman disease. Accumulation of large histiocytes with characteristic emperipolesis.
Cutaneous Rosai–Dorfman disease with spindle cells. Spindle cell morphology of Rosai–Dorfman disease histiocytes with prominent perivascular plasma cells within a fibrotic stroma.
Rosai–Dorfman disease. Immunohistochemistry for S100 highlights Rosai–Dorfman histiocytes with characteristic emperipolesis.
Rosai–Dorfman disease. Immunohistochemistry for the transcription factor OCT2 highlights Rosai–Dorfman histiocytes.
Rosai–Dorfman disease. Immunohistochemistry for cyclin D1 highlights Rosai–Dorfman histiocytes.
Cutaneous Rosai–Dorfman disease. The dermis shows a non-circumscribed lesion with pale-staining areas (rich in histiocytes) and dark-staining areas (rich in lymphocytes and plasma cells).
Cutaneous Rosai–Dorfman disease. The pale-staining areas are rich in histiocytes, while the dark-staining areas are rich in plasma cells and lymphocytes. This lesion also shows fibrosis.
Cutaneous Rosai–Dorfman disease. The distinctive histiocytes of Rosai–Dorfman disease are very large, with pale-staining cytoplasm, round nuclei, and large nucleoli. Plasma cells are found in the cytoplasm of the histiocytes (emperipolesis).
Cutaneous Rosai–Dorfman disease. Not all histiocytes have diagnostic morphology. In this field, there are foamy histiocytes (probably reactive in nature) admixed with histiocytes with prominent nucleoli. Emperipolesis is not evident.
Cutaneous Rosai–Dorfman disease mimicking chronic inflammation. This example shows marked infiltration of lymphocytes and plasma cells in the dermis and subcutis, suggestive of an inflammatory process.
Cutaneous Rosai–Dorfman disease mimicking chronic inflammation. The subcutaneous tissue shows extensive infiltration of lymphocytes and plasma cells.

Q: Immunohistochemically, the large histiocytes in Rosai-Dorfman Disease are classically positive for [...] (which also beautifully highlights the engulfed intact cells), but characteristically lack CD1a and CD207 (langerin).
Rosai–Dorfman disease. Immunohistochemistry for S100 highlights Rosai–Dorfman histiocytes with characteristic emperipolesis.
A: S100
Back Extra: Rosai-Dorfman Disease
- Clinical: Multiple painless reddish-brown papules, nodules, or plaques are typical, with involvement of the trunk, head, and neck. Cutaneous RDD often resolves spontaneously, but extranodal disease may require surgical intervention if vital structures are compromised.
- Micro: Histologically, cutaneous RDD shows large histiocytes with pale-staining cytoplasm, round nuclei, and prominent nucleoli. Emperipolesis, the presence of intact hematopoietic cells within the histiocyte cytoplasm, is characteristic.
- Ancillary: Immunohistochemically, RDD histiocytes are S100-positive and often positive for OCT2, cyclin D1, and phosphorylated ERK. They lack CD1a and CD207 (langerin). Gain-of-function mutations in the MAPK/ERK pathway are common.
Reference Gallery:
Cutaneous Rosai–Dorfman disease. Nodular proliferation of enlarged histiocytes associated with plasma cells and fibrosis, occupying the dermis and subcutaneous tissue.
Cutaneous Rosai–Dorfman disease. Accumulation of large histiocytes with characteristic emperipolesis.
Cutaneous Rosai–Dorfman disease with spindle cells. Spindle cell morphology of Rosai–Dorfman disease histiocytes with prominent perivascular plasma cells within a fibrotic stroma.
Rosai–Dorfman disease. Immunohistochemistry for S100 highlights Rosai–Dorfman histiocytes with characteristic emperipolesis.
Rosai–Dorfman disease. Immunohistochemistry for the transcription factor OCT2 highlights Rosai–Dorfman histiocytes.
Rosai–Dorfman disease. Immunohistochemistry for cyclin D1 highlights Rosai–Dorfman histiocytes.
Cutaneous Rosai–Dorfman disease. The dermis shows a non-circumscribed lesion with pale-staining areas (rich in histiocytes) and dark-staining areas (rich in lymphocytes and plasma cells).
Cutaneous Rosai–Dorfman disease. The pale-staining areas are rich in histiocytes, while the dark-staining areas are rich in plasma cells and lymphocytes. This lesion also shows fibrosis.
Cutaneous Rosai–Dorfman disease. The distinctive histiocytes of Rosai–Dorfman disease are very large, with pale-staining cytoplasm, round nuclei, and large nucleoli. Plasma cells are found in the cytoplasm of the histiocytes (emperipolesis).
Cutaneous Rosai–Dorfman disease. Not all histiocytes have diagnostic morphology. In this field, there are foamy histiocytes (probably reactive in nature) admixed with histiocytes with prominent nucleoli. Emperipolesis is not evident.
Cutaneous Rosai–Dorfman disease mimicking chronic inflammation. This example shows marked infiltration of lymphocytes and plasma cells in the dermis and subcutis, suggestive of an inflammatory process.
Cutaneous Rosai–Dorfman disease mimicking chronic inflammation. The subcutaneous tissue shows extensive infiltration of lymphocytes and plasma cells.

Q: At low magnification, cutaneous lesions of [...] classically exhibit a distinctive alternating pattern of pale-staining zones (rich in large histiocytes) and dark-staining zones (rich in lymphocytes and plasma cells).
Cutaneous Rosai–Dorfman disease. The dermis shows a non-circumscribed lesion with pale-staining areas (rich in histiocytes) and dark-staining areas (rich in lymphocytes and plasma cells).
Cutaneous Rosai–Dorfman disease. The pale-staining areas are rich in histiocytes, while the dark-staining areas are rich in plasma cells and lymphocytes. This lesion also shows fibrosis.
A: Rosai-Dorfman Disease
Back Extra: Rosai-Dorfman Disease
- Clinical: Multiple painless reddish-brown papules, nodules, or plaques are typical, with involvement of the trunk, head, and neck. Cutaneous RDD often resolves spontaneously, but extranodal disease may require surgical intervention if vital structures are compromised.
- Micro: Histologically, cutaneous RDD shows large histiocytes with pale-staining cytoplasm, round nuclei, and prominent nucleoli. Emperipolesis, the presence of intact hematopoietic cells within the histiocyte cytoplasm, is characteristic.
- Ancillary: Immunohistochemically, RDD histiocytes are S100-positive and often positive for OCT2, cyclin D1, and phosphorylated ERK. They lack CD1a and CD207 (langerin). Gain-of-function mutations in the MAPK/ERK pathway are common.
Reference Gallery:
Cutaneous Rosai–Dorfman disease. Nodular proliferation of enlarged histiocytes associated with plasma cells and fibrosis, occupying the dermis and subcutaneous tissue.
Cutaneous Rosai–Dorfman disease. Accumulation of large histiocytes with characteristic emperipolesis.
Cutaneous Rosai–Dorfman disease with spindle cells. Spindle cell morphology of Rosai–Dorfman disease histiocytes with prominent perivascular plasma cells within a fibrotic stroma.
Rosai–Dorfman disease. Immunohistochemistry for S100 highlights Rosai–Dorfman histiocytes with characteristic emperipolesis.
Rosai–Dorfman disease. Immunohistochemistry for the transcription factor OCT2 highlights Rosai–Dorfman histiocytes.
Rosai–Dorfman disease. Immunohistochemistry for cyclin D1 highlights Rosai–Dorfman histiocytes.
Cutaneous Rosai–Dorfman disease. The dermis shows a non-circumscribed lesion with pale-staining areas (rich in histiocytes) and dark-staining areas (rich in lymphocytes and plasma cells).
Cutaneous Rosai–Dorfman disease. The pale-staining areas are rich in histiocytes, while the dark-staining areas are rich in plasma cells and lymphocytes. This lesion also shows fibrosis.
Cutaneous Rosai–Dorfman disease. The distinctive histiocytes of Rosai–Dorfman disease are very large, with pale-staining cytoplasm, round nuclei, and large nucleoli. Plasma cells are found in the cytoplasm of the histiocytes (emperipolesis).
Cutaneous Rosai–Dorfman disease. Not all histiocytes have diagnostic morphology. In this field, there are foamy histiocytes (probably reactive in nature) admixed with histiocytes with prominent nucleoli. Emperipolesis is not evident.
Cutaneous Rosai–Dorfman disease mimicking chronic inflammation. This example shows marked infiltration of lymphocytes and plasma cells in the dermis and subcutis, suggestive of an inflammatory process.
Cutaneous Rosai–Dorfman disease mimicking chronic inflammation. The subcutaneous tissue shows extensive infiltration of lymphocytes and plasma cells.

Q: A clinical presentation of high fever and exaggerated skin manifestations—such as indurations that progress to blisters, bullae, and necrotic ulcers—following a mosquito bite is characteristic of [...].
Severe mosquito bite allergy. The bite area becomes indurated, forming blisters and bullae that break down into necrotic ulcers that heal over 2–3 weeks, leaving scars.
Severe mosquito bite allergy. The bite area becomes indurated, forming blisters and bullae that break down into necrotic ulcers that heal over 2–3 weeks, leaving scars.
A: Severe Mosquito Bite Allergy
Back Extra: Severe Mosquito Bite Allergy
- Clinical: Severe mosquito bite allergy is characterized by high fever and severe skin manifestations after mosquito bites, including blisters, bullae, and indurations.
- Micro: Histologically, there is a variably dense infiltrate of small to large atypical lymphocytes with a perivascular distribution in the dermis and subcutaneous tissue.
- Ancillary: Most cases exhibit an NK-cell immunophenotype, positive for CD16, CD56, and cytotoxic markers, and EBV-encoded small RNA (EBER) by in situ hybridization.
Reference Gallery:
Severe mosquito bite allergy. The bite area becomes indurated, forming blisters and bullae that break down into necrotic ulcers that heal over 2–3 weeks, leaving scars.
Severe mosquito bite allergy. The bite area becomes indurated, forming blisters and bullae that break down into necrotic ulcers that heal over 2–3 weeks, leaving scars.
Severe mosquito bite allergy. The bite area becomes indurated, forming blisters and bullae that break down into necrotic ulcers that heal over 2–3 weeks, leaving scars.
Severe mosquito bite allergy. There is a variably dense infiltrate, with a perivascular distribution in the dermis and ulceration of the epidermis.
Severe mosquito bite allergy. There is a variably dense infiltrate, with a perivascular distribution in the dermis and ulceration of the epidermis.
Severe mosquito bite allergy. The infiltrate corresponds to small, medium, and large atypical lymphocytes intermixed with eosinophils.
Severe mosquito bite allergy. The infiltrate corresponds to small, medium, and large atypical lymphocytes intermixed with eosinophils.

Q: Microscopically, the skin lesions of Severe Mosquito Bite Allergy demonstrate a variably dense perivascular infiltrate of small to large atypical lymphocytes characteristically intermixed with [...].
Severe mosquito bite allergy. The infiltrate corresponds to small, medium, and large atypical lymphocytes intermixed with eosinophils.
Severe mosquito bite allergy. The infiltrate corresponds to small, medium, and large atypical lymphocytes intermixed with eosinophils.
A: eosinophils
Back Extra: Severe Mosquito Bite Allergy
- Clinical: Severe mosquito bite allergy is characterized by high fever and severe skin manifestations after mosquito bites, including blisters, bullae, and indurations.
- Micro: Histologically, there is a variably dense infiltrate of small to large atypical lymphocytes with a perivascular distribution in the dermis and subcutaneous tissue.
- Ancillary: Most cases exhibit an NK-cell immunophenotype, positive for CD16, CD56, and cytotoxic markers, and EBV-encoded small RNA (EBER) by in situ hybridization.
Reference Gallery:
Severe mosquito bite allergy. The bite area becomes indurated, forming blisters and bullae that break down into necrotic ulcers that heal over 2–3 weeks, leaving scars.
Severe mosquito bite allergy. The bite area becomes indurated, forming blisters and bullae that break down into necrotic ulcers that heal over 2–3 weeks, leaving scars.
Severe mosquito bite allergy. The bite area becomes indurated, forming blisters and bullae that break down into necrotic ulcers that heal over 2–3 weeks, leaving scars.
Severe mosquito bite allergy. There is a variably dense infiltrate, with a perivascular distribution in the dermis and ulceration of the epidermis.
Severe mosquito bite allergy. There is a variably dense infiltrate, with a perivascular distribution in the dermis and ulceration of the epidermis.
Severe mosquito bite allergy. The infiltrate corresponds to small, medium, and large atypical lymphocytes intermixed with eosinophils.
Severe mosquito bite allergy. The infiltrate corresponds to small, medium, and large atypical lymphocytes intermixed with eosinophils.

Q: Patients with Sézary Syndrome classically present with severe pruritus, palmar hyperkeratosis, and generalized [...].
Sézary syndrome. Generalized (pigmented) erythroderma with scratch effects.
Sézary syndrome. Generalized skin involvement (erythroderma), with palmar hyperkeratosis and onychodystrophy.
A: erythroderma
Back Extra: Sézary Syndrome
- Clinical: Patients with Sézary Syndrome often present with generalized erythroderma, pruritus, alopecia, and palmar hyperkeratosis.
- Micro: Sézary cells are large atypical lymphocytes with cerebriform nuclei, often found in peripheral blood, skin, and lymph nodes.
- Ancillary: The neoplastic T cells in Sézary Syndrome show a CD3+, CD4+, CD8− phenotype and frequently lose expression of CD7 and CD26.
Reference Gallery:
Sézary syndrome. Generalized (pigmented) erythroderma with scratch effects.
Sézary syndrome. Perivascular infiltration with atypical lymphoid cells in superficial dermis.
Sézary syndrome. Higher magnification shows atypical lymphoid cells with cerebriform morphology.
Sézary syndrome. Generalized skin involvement (erythroderma), with palmar hyperkeratosis and onychodystrophy.
Sézary syndrome. Band-like infiltrate of atypical lymphoid cells in superficial dermis, with formation of Pautrier microabscesses.
Sézary syndrome. Strong expression of PD1 (CD279) by the atypical T cells.
Sézary syndrome. Electron micrograph of a Sézary cell showing nuclei with invaginated nuclear membranes and deep nuclear clefting.
Sézary syndrome. Atypical lymphocytes characteristic of Sézary syndrome.
Sézary syndrome. Sézary cells typically show a CD3+/CD4+/CD8− immunophenotype. The loss of CD7 and CD26 is common. Decreased expression of CD2 and/or CD5 is also seen. They are typically αβ T cells. The expression of CD30 is often associated with large cell transformation in mycosis fungoides and Sézary syndrome. Of note, the enumeration of neoplastic cells by flow cytometry should not be simply based on CD7−/CD4+ or CD26−/CD4+ immunophenotype, because a subset of normal/reactive T cells can be CD7− and/or CD26−. Determination of immunophenotypic aberrancies offers a better way to enumerate neoplastic T cells {32667737}.

Q: The hallmark atypical lymphocytes found in the skin, lymph nodes, and peripheral blood of patients with Sézary Syndrome feature highly convoluted, [...] nuclei.
Sézary syndrome. Higher magnification shows atypical lymphoid cells with cerebriform morphology.
Sézary syndrome. Electron micrograph of a Sézary cell showing nuclei with invaginated nuclear membranes and deep nuclear clefting.
Sézary syndrome. Atypical lymphocytes characteristic of Sézary syndrome.
A: cerebriform
Back Extra: Sézary Syndrome
- Clinical: Patients with Sézary Syndrome often present with generalized erythroderma, pruritus, alopecia, and palmar hyperkeratosis.
- Micro: Sézary cells are large atypical lymphocytes with cerebriform nuclei, often found in peripheral blood, skin, and lymph nodes.
- Ancillary: The neoplastic T cells in Sézary Syndrome show a CD3+, CD4+, CD8− phenotype and frequently lose expression of CD7 and CD26.
Reference Gallery:
Sézary syndrome. Generalized (pigmented) erythroderma with scratch effects.
Sézary syndrome. Perivascular infiltration with atypical lymphoid cells in superficial dermis.
Sézary syndrome. Higher magnification shows atypical lymphoid cells with cerebriform morphology.
Sézary syndrome. Generalized skin involvement (erythroderma), with palmar hyperkeratosis and onychodystrophy.
Sézary syndrome. Band-like infiltrate of atypical lymphoid cells in superficial dermis, with formation of Pautrier microabscesses.
Sézary syndrome. Strong expression of PD1 (CD279) by the atypical T cells.
Sézary syndrome. Electron micrograph of a Sézary cell showing nuclei with invaginated nuclear membranes and deep nuclear clefting.
Sézary syndrome. Atypical lymphocytes characteristic of Sézary syndrome.
Sézary syndrome. Sézary cells typically show a CD3+/CD4+/CD8− immunophenotype. The loss of CD7 and CD26 is common. Decreased expression of CD2 and/or CD5 is also seen. They are typically αβ T cells. The expression of CD30 is often associated with large cell transformation in mycosis fungoides and Sézary syndrome. Of note, the enumeration of neoplastic cells by flow cytometry should not be simply based on CD7−/CD4+ or CD26−/CD4+ immunophenotype, because a subset of normal/reactive T cells can be CD7− and/or CD26−. Determination of immunophenotypic aberrancies offers a better way to enumerate neoplastic T cells {32667737}.

Q: By flow cytometry, the neoplastic CD4+ T cells in Sézary Syndrome frequently demonstrate an aberrant loss of [...].
Sézary syndrome. Sézary cells typically show a CD3+/CD4+/CD8− immunophenotype. The loss of CD7 and CD26 is common. Decreased expression of CD2 and/or CD5 is also seen. They are typically αβ T cells. The expression of CD30 is often associated with large cell transformation in mycosis fungoides and Sézary syndrome. Of note, the enumeration of neoplastic cells by flow cytometry should not be simply based on CD7−/CD4+ or CD26−/CD4+ immunophenotype, because a subset of normal/reactive T cells can be CD7− and/or CD26−. Determination of immunophenotypic aberrancies offers a better way to enumerate neoplastic T cells {32667737}.
A: CD7 and CD26
Back Extra: Sézary Syndrome
- Clinical: Patients with Sézary Syndrome often present with generalized erythroderma, pruritus, alopecia, and palmar hyperkeratosis.
- Micro: Sézary cells are large atypical lymphocytes with cerebriform nuclei, often found in peripheral blood, skin, and lymph nodes.
- Ancillary: The neoplastic T cells in Sézary Syndrome show a CD3+, CD4+, CD8− phenotype and frequently lose expression of CD7 and CD26.
Reference Gallery:
Sézary syndrome. Generalized (pigmented) erythroderma with scratch effects.
Sézary syndrome. Perivascular infiltration with atypical lymphoid cells in superficial dermis.
Sézary syndrome. Higher magnification shows atypical lymphoid cells with cerebriform morphology.
Sézary syndrome. Generalized skin involvement (erythroderma), with palmar hyperkeratosis and onychodystrophy.
Sézary syndrome. Band-like infiltrate of atypical lymphoid cells in superficial dermis, with formation of Pautrier microabscesses.
Sézary syndrome. Strong expression of PD1 (CD279) by the atypical T cells.
Sézary syndrome. Electron micrograph of a Sézary cell showing nuclei with invaginated nuclear membranes and deep nuclear clefting.
Sézary syndrome. Atypical lymphocytes characteristic of Sézary syndrome.
Sézary syndrome. Sézary cells typically show a CD3+/CD4+/CD8− immunophenotype. The loss of CD7 and CD26 is common. Decreased expression of CD2 and/or CD5 is also seen. They are typically αβ T cells. The expression of CD30 is often associated with large cell transformation in mycosis fungoides and Sézary syndrome. Of note, the enumeration of neoplastic cells by flow cytometry should not be simply based on CD7−/CD4+ or CD26−/CD4+ immunophenotype, because a subset of normal/reactive T cells can be CD7− and/or CD26−. Determination of immunophenotypic aberrancies offers a better way to enumerate neoplastic T cells {32667737}.

Q: In Subcutaneous Panniculitis-like T-cell Lymphoma, histologic examination classically shows atypical lymphocytes [...], often accompanied by fat necrosis.
Subcutaneous panniculitis-like T-cell lymphoma. Infiltrate of medium-sized atypical lymphocytes. Rimming of lipocytes by the neoplastic cells.
Subcutaneous panniculitis-like T-cell lymphoma. Subcutaneous lobular lymphocytic infiltrates are seen.
A: rimming adipocytes
Back Extra: Subcutaneous Panniculitis-like T-cell Lymphoma
- Clinical: Patients with Subcutaneous Panniculitis-like T-cell Lymphoma (SPTCL) typically present with tender, non-ulcerated nodules and may have constitutional symptoms like fever and malaise.
- Micro: Histologically, SPTCL shows medium-sized lymphocytes with irregular and hyperchromatic nuclei, often rimming adipocytes and causing fat necrosis.
- Ancillary: Immunohistochemistry reveals CD8-positive T cells with αβ heterodimer expression, and high Ki-67 proliferative activity, but negative for CD30 and EBV-encoded small RNA (EBER).
Reference Gallery:
Subcutaneous panniculitis-like T-cell lymphoma. Infiltrate of medium-sized atypical lymphocytes. Rimming of lipocytes by the neoplastic cells.
Subcutaneous panniculitis-like T-cell lymphoma. Expression of CD8 by the tumour cells.
Subcutaneous panniculitis-like T-cell lymphoma. Erythematous deep nodules involving the lower leg.
Subcutaneous panniculitis-like T-cell lymphoma. Subcutaneous lobular lymphocytic infiltrates are seen.

Q: The neoplastic cells in Subcutaneous Panniculitis-like T-cell Lymphoma typically express an αβ T-cell receptor and are characteristically positive for [...] on immunohistochemistry.
Subcutaneous panniculitis-like T-cell lymphoma. Expression of CD8 by the tumour cells.
A: CD8
Back Extra: Subcutaneous Panniculitis-like T-cell Lymphoma
- Clinical: Patients with Subcutaneous Panniculitis-like T-cell Lymphoma (SPTCL) typically present with tender, non-ulcerated nodules and may have constitutional symptoms like fever and malaise.
- Micro: Histologically, SPTCL shows medium-sized lymphocytes with irregular and hyperchromatic nuclei, often rimming adipocytes and causing fat necrosis.
- Ancillary: Immunohistochemistry reveals CD8-positive T cells with αβ heterodimer expression, and high Ki-67 proliferative activity, but negative for CD30 and EBV-encoded small RNA (EBER).
Reference Gallery:
Subcutaneous panniculitis-like T-cell lymphoma. Infiltrate of medium-sized atypical lymphocytes. Rimming of lipocytes by the neoplastic cells.
Subcutaneous panniculitis-like T-cell lymphoma. Expression of CD8 by the tumour cells.
Subcutaneous panniculitis-like T-cell lymphoma. Erythematous deep nodules involving the lower leg.
Subcutaneous panniculitis-like T-cell lymphoma. Subcutaneous lobular lymphocytic infiltrates are seen.

Q: Patients with Subcutaneous Panniculitis-like T-cell Lymphoma typically present clinically with erythematous, tender [...], which are often non-ulcerated.
Subcutaneous panniculitis-like T-cell lymphoma. Erythematous deep nodules involving the lower leg.
A: deep nodules
Back Extra: Subcutaneous Panniculitis-like T-cell Lymphoma
- Clinical: Patients with Subcutaneous Panniculitis-like T-cell Lymphoma (SPTCL) typically present with tender, non-ulcerated nodules and may have constitutional symptoms like fever and malaise.
- Micro: Histologically, SPTCL shows medium-sized lymphocytes with irregular and hyperchromatic nuclei, often rimming adipocytes and causing fat necrosis.
- Ancillary: Immunohistochemistry reveals CD8-positive T cells with αβ heterodimer expression, and high Ki-67 proliferative activity, but negative for CD30 and EBV-encoded small RNA (EBER).
Reference Gallery:
Subcutaneous panniculitis-like T-cell lymphoma. Infiltrate of medium-sized atypical lymphocytes. Rimming of lipocytes by the neoplastic cells.
Subcutaneous panniculitis-like T-cell lymphoma. Expression of CD8 by the tumour cells.
Subcutaneous panniculitis-like T-cell lymphoma. Erythematous deep nodules involving the lower leg.
Subcutaneous panniculitis-like T-cell lymphoma. Subcutaneous lobular lymphocytic infiltrates are seen.

Q: In T-Cell Prolymphocytic Leukemia, cutaneous involvement can manifest as a papuloerythroderma that classically spares the skin folds of the abdomen, a clinical finding known as the [...].
T-prolymphocytic leukaemia involving skin. Papuloerythroderma-like lesion sparing the skin folds of the abdomen (deck-chair sign).
T-prolymphocytic leukaemia involving skin. The skin lesion is composed of cobblestone-like flat-topped papules.
A: deck-chair sign
Back Extra: T-Cell Prolymphocytic Leukemia
- Clinical: T-Cell Prolymphocytic Leukemia (T-PLL) often presents with extreme lymphocytosis, anemia, thrombocytopenia, hepatosplenomegaly, and generalized lymphadenopathy. Cutaneous manifestations include papuloerythroderma and cobblestone-like flat-topped papules.
- Micro: Skin biopsy shows a perivascular and periadnexal infiltrate of small to medium-sized prolymphocytes with basophilic cytoplasm and prominent nucleoli.
- Ancillary: Neoplastic cells are positive for CD2, CD3, CD7, CD52, and negative for TdT, CD1a, CD16, and CD30. They also express cytoplasmic TCL1 and show clonal TR gene rearrangements.
Reference Gallery:
T-prolymphocytic leukaemia involving skin. Papuloerythroderma-like lesion sparing the skin folds of the abdomen (deck-chair sign).
T-prolymphocytic leukaemia involving skin. The skin lesion is composed of cobblestone-like flat-topped papules.
T-prolymphocytic leukaemia involving skin. Circulating T-prolymphocytic leukaemia cells are characterized by small to medium-sized cells with basophilic cytoplasm and prominent nucleoli.
T-prolymphocytic leukaemia involving skin. Skin involved by a lymphoid infiltrate in the superficial dermis, with focal infiltration into the rete ridges. The lymphoid cells are atypical and composed of predominantly small to medium-sized mature lymphocytes.
T-prolymphocytic leukaemia involving skin. CD3 is expressed by the majority of T cells within the dermis, as well as in the epidermis.
T-prolymphocytic leukaemia involving skin. The neoplastic cells are CD4-positive.
T-prolymphocytic leukaemia involving skin. The neoplastic cells in the skin involved by T-prolymphocytic leukaemia are small to medium in size, with round and mature chromatin.
T-prolymphocytic leukaemia involving skin. Infiltration of the superficial and deep dermis by perivascular and periadnexal lymphoid infiltrate.
T-prolymphocytic leukaemia involving skin. Flow cytometric analysis demonstrates a population of mature CD3+, CD2+, CD7+, and CD56− T cells. The CD3 shows a spectrum of expression in the T-cell population.

Q: The circulating neoplastic cells in T-Cell Prolymphocytic Leukemia are typically small to medium-sized with basophilic cytoplasm and [...], giving them their distinct "prolymphocytic" appearance.
T-prolymphocytic leukaemia involving skin. Circulating T-prolymphocytic leukaemia cells are characterized by small to medium-sized cells with basophilic cytoplasm and prominent nucleoli.
A: prominent nucleoli
Back Extra: T-Cell Prolymphocytic Leukemia
- Clinical: T-Cell Prolymphocytic Leukemia (T-PLL) often presents with extreme lymphocytosis, anemia, thrombocytopenia, hepatosplenomegaly, and generalized lymphadenopathy. Cutaneous manifestations include papuloerythroderma and cobblestone-like flat-topped papules.
- Micro: Skin biopsy shows a perivascular and periadnexal infiltrate of small to medium-sized prolymphocytes with basophilic cytoplasm and prominent nucleoli.
- Ancillary: Neoplastic cells are positive for CD2, CD3, CD7, CD52, and negative for TdT, CD1a, CD16, and CD30. They also express cytoplasmic TCL1 and show clonal TR gene rearrangements.
Reference Gallery:
T-prolymphocytic leukaemia involving skin. Papuloerythroderma-like lesion sparing the skin folds of the abdomen (deck-chair sign).
T-prolymphocytic leukaemia involving skin. The skin lesion is composed of cobblestone-like flat-topped papules.
T-prolymphocytic leukaemia involving skin. Circulating T-prolymphocytic leukaemia cells are characterized by small to medium-sized cells with basophilic cytoplasm and prominent nucleoli.
T-prolymphocytic leukaemia involving skin. Skin involved by a lymphoid infiltrate in the superficial dermis, with focal infiltration into the rete ridges. The lymphoid cells are atypical and composed of predominantly small to medium-sized mature lymphocytes.
T-prolymphocytic leukaemia involving skin. CD3 is expressed by the majority of T cells within the dermis, as well as in the epidermis.
T-prolymphocytic leukaemia involving skin. The neoplastic cells are CD4-positive.
T-prolymphocytic leukaemia involving skin. The neoplastic cells in the skin involved by T-prolymphocytic leukaemia are small to medium in size, with round and mature chromatin.
T-prolymphocytic leukaemia involving skin. Infiltration of the superficial and deep dermis by perivascular and periadnexal lymphoid infiltrate.
T-prolymphocytic leukaemia involving skin. Flow cytometric analysis demonstrates a population of mature CD3+, CD2+, CD7+, and CD56− T cells. The CD3 shows a spectrum of expression in the T-cell population.

Q: Skin biopsies of T-Cell Prolymphocytic Leukemia typically demonstrate an atypical lymphoid infiltrate of mature lymphocytes that classically follows a [...] distribution in the superficial and deep dermis.
T-prolymphocytic leukaemia involving skin. Infiltration of the superficial and deep dermis by perivascular and periadnexal lymphoid infiltrate.
A: perivascular and periadnexal
Back Extra: T-Cell Prolymphocytic Leukemia
- Clinical: T-Cell Prolymphocytic Leukemia (T-PLL) often presents with extreme lymphocytosis, anemia, thrombocytopenia, hepatosplenomegaly, and generalized lymphadenopathy. Cutaneous manifestations include papuloerythroderma and cobblestone-like flat-topped papules.
- Micro: Skin biopsy shows a perivascular and periadnexal infiltrate of small to medium-sized prolymphocytes with basophilic cytoplasm and prominent nucleoli.
- Ancillary: Neoplastic cells are positive for CD2, CD3, CD7, CD52, and negative for TdT, CD1a, CD16, and CD30. They also express cytoplasmic TCL1 and show clonal TR gene rearrangements.
Reference Gallery:
T-prolymphocytic leukaemia involving skin. Papuloerythroderma-like lesion sparing the skin folds of the abdomen (deck-chair sign).
T-prolymphocytic leukaemia involving skin. The skin lesion is composed of cobblestone-like flat-topped papules.
T-prolymphocytic leukaemia involving skin. Circulating T-prolymphocytic leukaemia cells are characterized by small to medium-sized cells with basophilic cytoplasm and prominent nucleoli.
T-prolymphocytic leukaemia involving skin. Skin involved by a lymphoid infiltrate in the superficial dermis, with focal infiltration into the rete ridges. The lymphoid cells are atypical and composed of predominantly small to medium-sized mature lymphocytes.
T-prolymphocytic leukaemia involving skin. CD3 is expressed by the majority of T cells within the dermis, as well as in the epidermis.
T-prolymphocytic leukaemia involving skin. The neoplastic cells are CD4-positive.
T-prolymphocytic leukaemia involving skin. The neoplastic cells in the skin involved by T-prolymphocytic leukaemia are small to medium in size, with round and mature chromatin.
T-prolymphocytic leukaemia involving skin. Infiltration of the superficial and deep dermis by perivascular and periadnexal lymphoid infiltrate.
T-prolymphocytic leukaemia involving skin. Flow cytometric analysis demonstrates a population of mature CD3+, CD2+, CD7+, and CD56− T cells. The CD3 shows a spectrum of expression in the T-cell population.

Q: A benign melanocytic proliferation on the palms or soles that typically appears as a brownish-black macule and classically shows a parallel furrow pattern on dermoscopy is an [...].
Acral naevus. Brownish papule on the palm.
Acral naevus. Black macule on the sole of a 56-year-old woman.
Acral naevus. Dermoscopic finding of acral naevus. The parallel furrow and reticular pattern is seen in the patient of <<37891>>.
A: acral nevus
Back Extra: Acral Naevus
- Clinical: Acral naevi are common, occurring in more than a third of individuals, and their incidence peaks in the third and fourth decades of life. They appear as brownish to black small macules or flat papules.
- Micro: Acral naevi are relatively small and circumscribed, and they can be junctional, compound, or intradermal. Naevus cells are arranged as single units and variably sized nests.
- Ancillary: Acral naevi express melanocytic markers, which can help reveal subtle proliferations in nail matrix naevus (NMN). Acral naevi harbour BRAF or NRAS mutations.
Reference Gallery:
Acral compound naevus. Variably sized junctional proliferation with nests in the epidermis and the dermis.
Nail matrix naevus. Black linear band on the left third fingernail of a 2-year-old girl.
Nail matrix naevus. Dermoscopic finding. Black to brownish band, measuring 3 mm in width, on the fingernail of the same patient in <<34173>>.
Nail matrix naevus. There are variably sized junctional nests and single cells in the nail matrix.
Acral naevus. Dermoscopic features.
Acral naevus. Brownish papule on the palm.
Acral naevus. Black macule on the sole of a 56-year-old woman.
Acral naevus. Dermoscopic finding of acral naevus. The parallel furrow and reticular pattern is seen in the patient of <<37891>>.
Acral naevus. Acral compound naevus. Nests in the epidermis and dermis.
Acral naevus. Melan-A staining shows nests and single-cell proliferation in epidermis and dermis.

Q: When an acral nevus occurs in the nail unit (nail matrix nevus), it classically presents as a black longitudinal band on the nail plate, a clinical finding known as longitudinal [...].
Nail matrix naevus. Black linear band on the left third fingernail of a 2-year-old girl.
Nail matrix naevus. Dermoscopic finding. Black to brownish band, measuring 3 mm in width, on the fingernail of the same patient in <<34173>>.
Nail matrix naevus. There are variably sized junctional nests and single cells in the nail matrix.
A: melanonychia
Back Extra: Acral Naevus
- Clinical: Acral naevi are common, occurring in more than a third of individuals, and their incidence peaks in the third and fourth decades of life. They appear as brownish to black small macules or flat papules.
- Micro: Acral naevi are relatively small and circumscribed, and they can be junctional, compound, or intradermal. Naevus cells are arranged as single units and variably sized nests.
- Ancillary: Acral naevi express melanocytic markers, which can help reveal subtle proliferations in nail matrix naevus (NMN). Acral naevi harbour BRAF or NRAS mutations.
Reference Gallery:
Acral compound naevus. Variably sized junctional proliferation with nests in the epidermis and the dermis.
Nail matrix naevus. Black linear band on the left third fingernail of a 2-year-old girl.
Nail matrix naevus. Dermoscopic finding. Black to brownish band, measuring 3 mm in width, on the fingernail of the same patient in <<34173>>.
Nail matrix naevus. There are variably sized junctional nests and single cells in the nail matrix.
Acral naevus. Dermoscopic features.
Acral naevus. Brownish papule on the palm.
Acral naevus. Black macule on the sole of a 56-year-old woman.
Acral naevus. Dermoscopic finding of acral naevus. The parallel furrow and reticular pattern is seen in the patient of <<37891>>.
Acral naevus. Acral compound naevus. Nests in the epidermis and dermis.
Acral naevus. Melan-A staining shows nests and single-cell proliferation in epidermis and dermis.

Q: Microscopically, an acral nevus is a circumscribed proliferation of melanocytes arranged in nests and single units, which can be highlighted by immunohistochemical stains such as [...].
Acral compound naevus. Variably sized junctional proliferation with nests in the epidermis and the dermis.
Acral naevus. Acral compound naevus. Nests in the epidermis and dermis.
Acral naevus. Melan-A staining shows nests and single-cell proliferation in epidermis and dermis.
A: Melan-A
Back Extra: Acral Naevus
- Clinical: Acral naevi are common, occurring in more than a third of individuals, and their incidence peaks in the third and fourth decades of life. They appear as brownish to black small macules or flat papules.
- Micro: Acral naevi are relatively small and circumscribed, and they can be junctional, compound, or intradermal. Naevus cells are arranged as single units and variably sized nests.
- Ancillary: Acral naevi express melanocytic markers, which can help reveal subtle proliferations in nail matrix naevus (NMN). Acral naevi harbour BRAF or NRAS mutations.
Reference Gallery:
Acral compound naevus. Variably sized junctional proliferation with nests in the epidermis and the dermis.
Nail matrix naevus. Black linear band on the left third fingernail of a 2-year-old girl.
Nail matrix naevus. Dermoscopic finding. Black to brownish band, measuring 3 mm in width, on the fingernail of the same patient in <<34173>>.
Nail matrix naevus. There are variably sized junctional nests and single cells in the nail matrix.
Acral naevus. Dermoscopic features.
Acral naevus. Brownish papule on the palm.
Acral naevus. Black macule on the sole of a 56-year-old woman.
Acral naevus. Dermoscopic finding of acral naevus. The parallel furrow and reticular pattern is seen in the patient of <<37891>>.
Acral naevus. Acral compound naevus. Nests in the epidermis and dermis.
Acral naevus. Melan-A staining shows nests and single-cell proliferation in epidermis and dermis.

Q: On dermoscopic evaluation, an Acral Naevus located on the palms or soles often displays a characteristic benign [...] and reticular pattern.
Acral naevus. Black macule on the sole of a 56-year-old woman.
Acral naevus. Dermoscopic finding of acral naevus. The parallel furrow and reticular pattern is seen in the patient of <<37891>>.
A: parallel furrow
Back Extra: Acral Naevus
- Clinical: Acral naevi are common, occurring in more than a third of individuals, and their incidence peaks in the third and fourth decades of life. They are brownish to black small macules or flat papules.
- Micro: Acral naevi are relatively small and circumscribed, and they can be junctional, compound, or intradermal. Naevus cells are arranged as single units and variably sized nests.
- Ancillary: Immunohistochemistry shows that acral naevi express melanocytic markers, which can help reveal subtle proliferations in nail matrix naevus.
Reference Gallery:
Nail matrix naevus. Black linear band on the left third fingernail of a 2-year-old girl.
Nail matrix naevus. Dermoscopic finding. Black to brownish band, measuring 3 mm in width, on the fingernail of the same patient in <<34173>>.
Nail matrix naevus. There are variably sized junctional nests and single cells in the nail matrix.
Acral naevus. Dermoscopic features.
Acral naevus. Brownish papule on the palm.
Acral naevus. Black macule on the sole of a 56-year-old woman.
Acral naevus. Dermoscopic finding of acral naevus. The parallel furrow and reticular pattern is seen in the patient of <<37891>>.
Acral naevus. Acral compound naevus. Nests in the epidermis and dermis.
Acral naevus. Melan-A staining shows nests and single-cell proliferation in epidermis and dermis.

Q: Microscopically, an Acral Naevus is a relatively small, circumscribed melanocytic proliferation characterized by cells arranged as single units and variably sized [...] at the dermoepidermal junction and/or within the dermis.
Nail matrix naevus. There are variably sized junctional nests and single cells in the nail matrix.
Acral naevus. Acral compound naevus. Nests in the epidermis and dermis.
A: nests
Back Extra: Acral Naevus
- Clinical: Acral naevi are common, occurring in more than a third of individuals, and their incidence peaks in the third and fourth decades of life. They are brownish to black small macules or flat papules.
- Micro: Acral naevi are relatively small and circumscribed, and they can be junctional, compound, or intradermal. Naevus cells are arranged as single units and variably sized nests.
- Ancillary: Immunohistochemistry shows that acral naevi express melanocytic markers, which can help reveal subtle proliferations in nail matrix naevus.
Reference Gallery:
Nail matrix naevus. Black linear band on the left third fingernail of a 2-year-old girl.
Nail matrix naevus. Dermoscopic finding. Black to brownish band, measuring 3 mm in width, on the fingernail of the same patient in <<34173>>.
Nail matrix naevus. There are variably sized junctional nests and single cells in the nail matrix.
Acral naevus. Dermoscopic features.
Acral naevus. Brownish papule on the palm.
Acral naevus. Black macule on the sole of a 56-year-old woman.
Acral naevus. Dermoscopic finding of acral naevus. The parallel furrow and reticular pattern is seen in the patient of <<37891>>.
Acral naevus. Acral compound naevus. Nests in the epidermis and dermis.
Acral naevus. Melan-A staining shows nests and single-cell proliferation in epidermis and dermis.

Q: In cases of an Acral Naevus involving the nail matrix or to highlight subtle melanocytic proliferations, an immunohistochemical stain such as [...] can be utilized.
Acral naevus. Melan-A staining shows nests and single-cell proliferation in epidermis and dermis.
A: Melan-A
Back Extra: Acral Naevus
- Clinical: Acral naevi are common, occurring in more than a third of individuals, and their incidence peaks in the third and fourth decades of life. They are brownish to black small macules or flat papules.
- Micro: Acral naevi are relatively small and circumscribed, and they can be junctional, compound, or intradermal. Naevus cells are arranged as single units and variably sized nests.
- Ancillary: Immunohistochemistry shows that acral naevi express melanocytic markers, which can help reveal subtle proliferations in nail matrix naevus.
Reference Gallery:
Nail matrix naevus. Black linear band on the left third fingernail of a 2-year-old girl.
Nail matrix naevus. Dermoscopic finding. Black to brownish band, measuring 3 mm in width, on the fingernail of the same patient in <<34173>>.
Nail matrix naevus. There are variably sized junctional nests and single cells in the nail matrix.
Acral naevus. Dermoscopic features.
Acral naevus. Brownish papule on the palm.
Acral naevus. Black macule on the sole of a 56-year-old woman.
Acral naevus. Dermoscopic finding of acral naevus. The parallel furrow and reticular pattern is seen in the patient of <<37891>>.
Acral naevus. Acral compound naevus. Nests in the epidermis and dermis.
Acral naevus. Melan-A staining shows nests and single-cell proliferation in epidermis and dermis.

Q: Histologically, BAP1-inactivated melanocytoma is characteristically composed of large, unpigmented, [...] melanocytes with vesicular nuclei, prominent nucleoli, and an associated sparse to dense lymphocytic infiltrate.
Combined BAP1-inactivated melanocytoma. Close-up of the large, unpigmented, epithelioid melanocytes with large pleomorphic nuclei, vesicular chromatin, abundant cytoplasm, distinct cell borders, and a sparse infiltrate of lymphocytes.
BAP1-inactivated melanocytoma. Dermal component with nests of mainly naevocytoid cells interspaced with loose sheets of large epithelioid melanocytes with abundant eosinophilic cytoplasm. No mitotic activity. Absence of top-down maturation.
A: epithelioid
Back Extra: BAP1-inactivated melanocytoma
- Clinical: BAP1-inactivated melanocytomas often present as inconspicuous, skin-coloured to reddish-brown, dome-shaped papules 4–12 mm in size.
- Micro: Histologically, these lesions consist of large, unpigmented, epithelioid melanocytes with vesicular nuclei and prominent nucleoli, often with a lymphocytic infiltrate.
- Ancillary: Immunohistochemistry shows complete loss of BAP1 expression in the tumour cells, which helps confirm the diagnosis.
Reference Gallery:
BAP1-inactivated melanocytoma. Reddish-brown, elevated, slightly asymmetrical papule on the upper arm.
Combined BAP1-inactivated melanocytoma. The conventional naevus on the left is composed of small, oval melanocytes, with the BAP1-inactivated melanocytoma composed of large, unpigmented, epithelioid melanocytes on the right.
Combined BAP1-inactivated melanocytoma. Close-up of the large, unpigmented, epithelioid melanocytes with large pleomorphic nuclei, vesicular chromatin, abundant cytoplasm, distinct cell borders, and a sparse infiltrate of lymphocytes.
BAP1-inactivated melanocytoma. Compound melanocytic proliferation with an intradermal component mixing nests and sheet-like patterns. Focal dense lymphocytic infiltrate (haematoxylin eosin saffron stain).
BAP1-inactivated melanocytoma. Dermal component with nests of mainly naevocytoid cells interspaced with loose sheets of large epithelioid melanocytes with abundant eosinophilic cytoplasm. No mitotic activity. Absence of top-down maturation.
BAP1-inactivated melanocytoma. BAP1 immunohistochemistry showing a diffuse loss of expression in the tumour cells (internal controls: intradermal keratinocytes and lymphocytes).

Q: Immunohistochemistry in BAP1-inactivated melanocytoma classically demonstrates a diffuse loss of [...] expression in the tumor cells (with retained expression in internal controls like keratinocytes and lymphocytes).
BAP1-inactivated melanocytoma. BAP1 immunohistochemistry showing a diffuse loss of expression in the tumour cells (internal controls: intradermal keratinocytes and lymphocytes).
A: BAP1
Back Extra: BAP1-inactivated melanocytoma
- Clinical: BAP1-inactivated melanocytomas often present as inconspicuous, skin-coloured to reddish-brown, dome-shaped papules 4–12 mm in size.
- Micro: Histologically, these lesions consist of large, unpigmented, epithelioid melanocytes with vesicular nuclei and prominent nucleoli, often with a lymphocytic infiltrate.
- Ancillary: Immunohistochemistry shows complete loss of BAP1 expression in the tumour cells, which helps confirm the diagnosis.
Reference Gallery:
BAP1-inactivated melanocytoma. Reddish-brown, elevated, slightly asymmetrical papule on the upper arm.
Combined BAP1-inactivated melanocytoma. The conventional naevus on the left is composed of small, oval melanocytes, with the BAP1-inactivated melanocytoma composed of large, unpigmented, epithelioid melanocytes on the right.
Combined BAP1-inactivated melanocytoma. Close-up of the large, unpigmented, epithelioid melanocytes with large pleomorphic nuclei, vesicular chromatin, abundant cytoplasm, distinct cell borders, and a sparse infiltrate of lymphocytes.
BAP1-inactivated melanocytoma. Compound melanocytic proliferation with an intradermal component mixing nests and sheet-like patterns. Focal dense lymphocytic infiltrate (haematoxylin eosin saffron stain).
BAP1-inactivated melanocytoma. Dermal component with nests of mainly naevocytoid cells interspaced with loose sheets of large epithelioid melanocytes with abundant eosinophilic cytoplasm. No mitotic activity. Absence of top-down maturation.
BAP1-inactivated melanocytoma. BAP1 immunohistochemistry showing a diffuse loss of expression in the tumour cells (internal controls: intradermal keratinocytes and lymphocytes).

Q: A patient presents with a skin-colored to reddish-brown, dome-shaped papule. If histology reveals a combined nevus containing a distinct population of large, unpigmented epithelioid melanocytes with associated lymphocytes, the most likely diagnosis is [...].
BAP1-inactivated melanocytoma. Reddish-brown, elevated, slightly asymmetrical papule on the upper arm.
Combined BAP1-inactivated melanocytoma. The conventional naevus on the left is composed of small, oval melanocytes, with the BAP1-inactivated melanocytoma composed of large, unpigmented, epithelioid melanocytes on the right.
A: BAP1-inactivated melanocytoma
Back Extra: BAP1-inactivated melanocytoma
- Clinical: BAP1-inactivated melanocytomas often present as inconspicuous, skin-coloured to reddish-brown, dome-shaped papules 4–12 mm in size.
- Micro: Histologically, these lesions consist of large, unpigmented, epithelioid melanocytes with vesicular nuclei and prominent nucleoli, often with a lymphocytic infiltrate.
- Ancillary: Immunohistochemistry shows complete loss of BAP1 expression in the tumour cells, which helps confirm the diagnosis.
Reference Gallery:
BAP1-inactivated melanocytoma. Reddish-brown, elevated, slightly asymmetrical papule on the upper arm.
Combined BAP1-inactivated melanocytoma. The conventional naevus on the left is composed of small, oval melanocytes, with the BAP1-inactivated melanocytoma composed of large, unpigmented, epithelioid melanocytes on the right.
Combined BAP1-inactivated melanocytoma. Close-up of the large, unpigmented, epithelioid melanocytes with large pleomorphic nuclei, vesicular chromatin, abundant cytoplasm, distinct cell borders, and a sparse infiltrate of lymphocytes.
BAP1-inactivated melanocytoma. Compound melanocytic proliferation with an intradermal component mixing nests and sheet-like patterns. Focal dense lymphocytic infiltrate (haematoxylin eosin saffron stain).
BAP1-inactivated melanocytoma. Dermal component with nests of mainly naevocytoid cells interspaced with loose sheets of large epithelioid melanocytes with abundant eosinophilic cytoplasm. No mitotic activity. Absence of top-down maturation.
BAP1-inactivated melanocytoma. BAP1 immunohistochemistry showing a diffuse loss of expression in the tumour cells (internal controls: intradermal keratinocytes and lymphocytes).

Q: Patients with BAP1-related tumour predisposition syndrome (BAP1-TPDS) classically present with multiple skin-colored to reddish-brown, dome-shaped papules on sun-exposed skin, which represent [...].
BAP1-related tumour predisposition syndrome. Skin lesions typical of BAP1-related tumour predisposition syndrome: multiple BAP1-inactivated naevi. Multiple skin-coloured to reddish-brown, dome-shaped, well-circumscribed papules on the right upper arm (BAP1-inactivated naevi), together with smaller, brown macules (common acquired naevi).
BAP1-related tumour predisposition syndrome. BAP1-inactivated naevi often present as reddish-brown, dome-shaped, well-circumscribed papules.
A: BAP1-inactivated melanocytic nevi
Back Extra: BAP1-related tumour predisposition syndrome (BAP1-TPDS)
- Clinical: Patients with BAP1-related tumour predisposition syndrome (BAP1-TPDS) often present with multiple BAP1-inactivated melanocytic naevi, which are typically skin-coloured to reddish-brown, dome-shaped, well-circumscribed papules on sun-exposed skin.
- Micro: BAP1-inactivated melanocytic naevi are predominantly intradermal, with an admixture of small naevoid cells and larger epithelioid cells, showing varying degrees of atypia and loss of nuclear BAP1 expression.
- Ancillary: Loss of nuclear BAP1 expression by immunohistochemistry is a key finding in BAP1-inactivated melanocytic naevi, and genetic testing of germline DNA confirms the diagnosis.
Reference Gallery:
BAP1-related tumour predisposition syndrome. Skin lesions typical of BAP1-related tumour predisposition syndrome: multiple BAP1-inactivated naevi. Multiple skin-coloured to reddish-brown, dome-shaped, well-circumscribed papules on the right upper arm (BAP1-inactivated naevi), together with smaller, brown macules (common acquired naevi).
BAP1-related tumour predisposition syndrome. BAP1-inactivated naevi often present as reddish-brown, dome-shaped, well-circumscribed papules.
BAP1-related tumour predisposition syndrome. BAP1-inactivated naevus. A symmetrical, well-circumscribed, predominantly intradermal tumour.
BAP1-inactivated naevus. Higher magnification shows enlarged, epithelioid melanocytes with distinct cell borders, abundant cytoplasm, and large nuclei with conspicuous nucleoli.
BAP1-inactivated naevus. BAP1 immunohistochemistry shows a loss of nuclear BAP1 expression in the large, epithelioid melanocytes, but not in the keratinocytes or the tumour-infiltrating lymphocytes.

Q: The characteristic skin lesions of BAP1-related tumour predisposition syndrome (BAP1-TPDS) are predominantly intradermal and feature a biphasic population of small nevoid cells admixed with larger, atypical [...].
BAP1-related tumour predisposition syndrome. BAP1-inactivated naevus. A symmetrical, well-circumscribed, predominantly intradermal tumour.
BAP1-inactivated naevus. Higher magnification shows enlarged, epithelioid melanocytes with distinct cell borders, abundant cytoplasm, and large nuclei with conspicuous nucleoli.
A: epithelioid melanocytes
Back Extra: BAP1-related tumour predisposition syndrome (BAP1-TPDS)
- Clinical: Patients with BAP1-related tumour predisposition syndrome (BAP1-TPDS) often present with multiple BAP1-inactivated melanocytic naevi, which are typically skin-coloured to reddish-brown, dome-shaped, well-circumscribed papules on sun-exposed skin.
- Micro: BAP1-inactivated melanocytic naevi are predominantly intradermal, with an admixture of small naevoid cells and larger epithelioid cells, showing varying degrees of atypia and loss of nuclear BAP1 expression.
- Ancillary: Loss of nuclear BAP1 expression by immunohistochemistry is a key finding in BAP1-inactivated melanocytic naevi, and genetic testing of germline DNA confirms the diagnosis.
Reference Gallery:
BAP1-related tumour predisposition syndrome. Skin lesions typical of BAP1-related tumour predisposition syndrome: multiple BAP1-inactivated naevi. Multiple skin-coloured to reddish-brown, dome-shaped, well-circumscribed papules on the right upper arm (BAP1-inactivated naevi), together with smaller, brown macules (common acquired naevi).
BAP1-related tumour predisposition syndrome. BAP1-inactivated naevi often present as reddish-brown, dome-shaped, well-circumscribed papules.
BAP1-related tumour predisposition syndrome. BAP1-inactivated naevus. A symmetrical, well-circumscribed, predominantly intradermal tumour.
BAP1-inactivated naevus. Higher magnification shows enlarged, epithelioid melanocytes with distinct cell borders, abundant cytoplasm, and large nuclei with conspicuous nucleoli.
BAP1-inactivated naevus. BAP1 immunohistochemistry shows a loss of nuclear BAP1 expression in the large, epithelioid melanocytes, but not in the keratinocytes or the tumour-infiltrating lymphocytes.

Q: By immunohistochemistry, the atypical epithelioid cells in the skin lesions of BAP1-related tumour predisposition syndrome (BAP1-TPDS) characteristically demonstrate a [...].
BAP1-inactivated naevus. BAP1 immunohistochemistry shows a loss of nuclear BAP1 expression in the large, epithelioid melanocytes, but not in the keratinocytes or the tumour-infiltrating lymphocytes.
A: loss of nuclear BAP1 expression
Back Extra: BAP1-related tumour predisposition syndrome (BAP1-TPDS)
- Clinical: Patients with BAP1-related tumour predisposition syndrome (BAP1-TPDS) often present with multiple BAP1-inactivated melanocytic naevi, which are typically skin-coloured to reddish-brown, dome-shaped, well-circumscribed papules on sun-exposed skin.
- Micro: BAP1-inactivated melanocytic naevi are predominantly intradermal, with an admixture of small naevoid cells and larger epithelioid cells, showing varying degrees of atypia and loss of nuclear BAP1 expression.
- Ancillary: Loss of nuclear BAP1 expression by immunohistochemistry is a key finding in BAP1-inactivated melanocytic naevi, and genetic testing of germline DNA confirms the diagnosis.
Reference Gallery:
BAP1-related tumour predisposition syndrome. Skin lesions typical of BAP1-related tumour predisposition syndrome: multiple BAP1-inactivated naevi. Multiple skin-coloured to reddish-brown, dome-shaped, well-circumscribed papules on the right upper arm (BAP1-inactivated naevi), together with smaller, brown macules (common acquired naevi).
BAP1-related tumour predisposition syndrome. BAP1-inactivated naevi often present as reddish-brown, dome-shaped, well-circumscribed papules.
BAP1-related tumour predisposition syndrome. BAP1-inactivated naevus. A symmetrical, well-circumscribed, predominantly intradermal tumour.
BAP1-inactivated naevus. Higher magnification shows enlarged, epithelioid melanocytes with distinct cell borders, abundant cytoplasm, and large nuclei with conspicuous nucleoli.
BAP1-inactivated naevus. BAP1 immunohistochemistry shows a loss of nuclear BAP1 expression in the large, epithelioid melanocytes, but not in the keratinocytes or the tumour-infiltrating lymphocytes.

Q: Grossly, Uveal Melanocytoma classically presents as a heavily pigmented, dark-gray to black mass that is discoid or [...].
Ciliary body melanocytoma. A resection specimen shows a heavily pigmented dome-shaped mass.
A: dome-shaped
Back Extra: Uveal Melanocytoma
- Clinical: Uveal melanocytoma typically presents as a discoid or dome-shaped dark-grey to black mass that can cause iris heterochromia and glaucoma.
- Micro: Melanocytomas are composed of large polygonal pigmented melanocytes with a low N:C ratio and bland nuclei. Bleaching is often required to evaluate the cells adequately.
- Ancillary: Uveal melanocytomas are positive for melan-A, HMB45, SOX10, MITF, and S100, and show a very low Ki-67 growth fraction (0-2%).
Reference Gallery:
Ciliary body melanocytoma transforming to uveal melanoma. H&E section showing a ciliary body melanocytoma (on the left) transforming to a uveal melanoma (on the right). Note the loss of pigment and the higher N:C ratio of the uveal melanoma cells.
Ciliary body melanocytoma. An unbleached section shows heavily melanized, polygonal melanocytic cells that are artefactially separated. Their nuclei are central to peripheral.
Uveal melanocytoma. FNAC shows a cluster of ovoid cells with centrally located small nuclei and intracytoplasmic pigment (Pap stain).
Ciliary body melanocytoma. A resection specimen shows a heavily pigmented dome-shaped mass.
Uveal melanocytoma. Polyhedral tumour cells with abundant cytoplasmic pigmentation that obscures nuclear features.
Uveal melanocytoma. Beaching allows for removal of cytoplasmic melanin pigment granules, revealing tumour cells with low N:C ratio and small round nuclei with inconspicuous nucleoli.
Iris melanocytoma. A 9-year-old girl with a pigmented iris tumour measuring approximately 3.4 mm in diameter and located in the lower nasal quadrant (between the 7 and 8 o’clock positions). Additionally, a smaller inferior crescent-like lesion is seen at the 6 o’clock position.

Q: Microscopically, Uveal Melanocytoma consists of large, heavily pigmented polygonal cells; due to the dense melanin, [...] is often required to properly evaluate the bland nuclei and low N:C ratio.
Uveal melanocytoma. Polyhedral tumour cells with abundant cytoplasmic pigmentation that obscures nuclear features.
Uveal melanocytoma. Beaching allows for removal of cytoplasmic melanin pigment granules, revealing tumour cells with low N:C ratio and small round nuclei with inconspicuous nucleoli.
A: bleaching
Back Extra: Uveal Melanocytoma
- Clinical: Uveal melanocytoma typically presents as a discoid or dome-shaped dark-grey to black mass that can cause iris heterochromia and glaucoma.
- Micro: Melanocytomas are composed of large polygonal pigmented melanocytes with a low N:C ratio and bland nuclei. Bleaching is often required to evaluate the cells adequately.
- Ancillary: Uveal melanocytomas are positive for melan-A, HMB45, SOX10, MITF, and S100, and show a very low Ki-67 growth fraction (0-2%).
Reference Gallery:
Ciliary body melanocytoma transforming to uveal melanoma. H&E section showing a ciliary body melanocytoma (on the left) transforming to a uveal melanoma (on the right). Note the loss of pigment and the higher N:C ratio of the uveal melanoma cells.
Ciliary body melanocytoma. An unbleached section shows heavily melanized, polygonal melanocytic cells that are artefactially separated. Their nuclei are central to peripheral.
Uveal melanocytoma. FNAC shows a cluster of ovoid cells with centrally located small nuclei and intracytoplasmic pigment (Pap stain).
Ciliary body melanocytoma. A resection specimen shows a heavily pigmented dome-shaped mass.
Uveal melanocytoma. Polyhedral tumour cells with abundant cytoplasmic pigmentation that obscures nuclear features.
Uveal melanocytoma. Beaching allows for removal of cytoplasmic melanin pigment granules, revealing tumour cells with low N:C ratio and small round nuclei with inconspicuous nucleoli.
Iris melanocytoma. A 9-year-old girl with a pigmented iris tumour measuring approximately 3.4 mm in diameter and located in the lower nasal quadrant (between the 7 and 8 o’clock positions). Additionally, a smaller inferior crescent-like lesion is seen at the 6 o’clock position.

Q: The characteristic bluish-gray to bluish-black color of a Blue Naevus is clinically attributed to the [...] of preferential blue color transmission.
Blue naevus. This relatively large lesion exemplifies the characteristic colour due to the Tyndall effect of preferential blue colour transmission.
A: Tyndall effect
Back Extra: Blue Naevus
- Clinical: Blue naevi are bluish-grey to bluish-black macules or papules, usually < 10 mm in diameter. Plaque-type blue naevi can be several centimetres in diameter and are present at birth or arise in early childhood.
- Micro: Dendritic blue naevus shows small, spindled, and dendritic melanocytes in a fibrotic background. Cellular blue naevus features well-circumscribed nests of lightly pigmented, fusiform to ovoid melanocytes.
- Ancillary: Melanocytes in blue naevi are usually positive for HMB45, SOX10, and melan-A. GNAQ, GNA11, PLCB4, or CYSLTR2 mutations are common in cellular blue naevi.
Reference Gallery:
Dendritic blue naevus. Poorly defined dermal hyperpigmented fibrosing proliferation.
Dendritic blue naevus. There are small spindled and dendritic melanocytes in a fibrotic background.
Blue naevus. This relatively large lesion exemplifies the characteristic colour due to the Tyndall effect of preferential blue colour transmission.
Cellular blue naevus. Symmetrical heavily pigmented nodule elevating the skin without ulceration.
Cellular blue naevus. Biphasic architecture with an upper intradermal, poorly delineated area of dendritic blue naevus and deep expansion pushing away the subcutis, with cellular nests of unpigmented melanocytes.
Cellular blue naevus. Higher magnification shows cellular nests of medium-sized fusiform to ovoid cells surrounded by heavily pigmented spindle cells.
Dendritic blue naevus. Poorly defined, hyperpigmented, fibrosing dermal proliferation.
Dendritic blue naevus. Small, poorly defined, spindled and dendritic dermal melanocytes.
Dendritic blue naevus. Higher magnification shows small spindled and dendritic melanocytes in a fasciculated fibrotic background.
Cellular blue naevus. Poorly delineated, spindled and fibrotic intradermal proliferation expanding deeply into the subcutis, with central myxoid/cystic changes surrounding cellular nests.
Cellular blue naevus. High-magnification view of the central area with myxoid/cystic changes surrounding cellular nests of bland, spindled, unpigmented melanocytes.
Plaque-type cellular blue naevus. Biphasic architecture, with a poorly delineated upper intradermal area of dendritic blue naevus and deep expansion extending into the subcutis with cellular nests of non-pigmented melanocytes.

Q: A classic histologic feature of the conventional Blue Naevus is a poorly defined dermal proliferation of heavily pigmented, spindled, and [...] melanocytes embedded in a fibrotic stroma.
Dendritic blue naevus. There are small spindled and dendritic melanocytes in a fibrotic background.
Dendritic blue naevus. Higher magnification shows small spindled and dendritic melanocytes in a fasciculated fibrotic background.
A: dendritic
Back Extra: Blue Naevus
- Clinical: Blue naevi are bluish-grey to bluish-black macules or papules, usually < 10 mm in diameter. Plaque-type blue naevi can be several centimetres in diameter and are present at birth or arise in early childhood.
- Micro: Dendritic blue naevus shows small, spindled, and dendritic melanocytes in a fibrotic background. Cellular blue naevus features well-circumscribed nests of lightly pigmented, fusiform to ovoid melanocytes.
- Ancillary: Melanocytes in blue naevi are usually positive for HMB45, SOX10, and melan-A. GNAQ, GNA11, PLCB4, or CYSLTR2 mutations are common in cellular blue naevi.
Reference Gallery:
Dendritic blue naevus. Poorly defined dermal hyperpigmented fibrosing proliferation.
Dendritic blue naevus. There are small spindled and dendritic melanocytes in a fibrotic background.
Blue naevus. This relatively large lesion exemplifies the characteristic colour due to the Tyndall effect of preferential blue colour transmission.
Cellular blue naevus. Symmetrical heavily pigmented nodule elevating the skin without ulceration.
Cellular blue naevus. Biphasic architecture with an upper intradermal, poorly delineated area of dendritic blue naevus and deep expansion pushing away the subcutis, with cellular nests of unpigmented melanocytes.
Cellular blue naevus. Higher magnification shows cellular nests of medium-sized fusiform to ovoid cells surrounded by heavily pigmented spindle cells.
Dendritic blue naevus. Poorly defined, hyperpigmented, fibrosing dermal proliferation.
Dendritic blue naevus. Small, poorly defined, spindled and dendritic dermal melanocytes.
Dendritic blue naevus. Higher magnification shows small spindled and dendritic melanocytes in a fasciculated fibrotic background.
Cellular blue naevus. Poorly delineated, spindled and fibrotic intradermal proliferation expanding deeply into the subcutis, with central myxoid/cystic changes surrounding cellular nests.
Cellular blue naevus. High-magnification view of the central area with myxoid/cystic changes surrounding cellular nests of bland, spindled, unpigmented melanocytes.
Plaque-type cellular blue naevus. Biphasic architecture, with a poorly delineated upper intradermal area of dendritic blue naevus and deep expansion extending into the subcutis with cellular nests of non-pigmented melanocytes.

Q: The cellular variant of a Blue Naevus typically features a biphasic architecture composed of an upper intradermal component and deep, pushing [...] of lightly pigmented or unpigmented fusiform-to-ovoid melanocytes.
Cellular blue naevus. Biphasic architecture with an upper intradermal, poorly delineated area of dendritic blue naevus and deep expansion pushing away the subcutis, with cellular nests of unpigmented melanocytes.
Cellular blue naevus. Higher magnification shows cellular nests of medium-sized fusiform to ovoid cells surrounded by heavily pigmented spindle cells.
A: cellular nests
Back Extra: Blue Naevus
- Clinical: Blue naevi are bluish-grey to bluish-black macules or papules, usually < 10 mm in diameter. Plaque-type blue naevi can be several centimetres in diameter and are present at birth or arise in early childhood.
- Micro: Dendritic blue naevus shows small, spindled, and dendritic melanocytes in a fibrotic background. Cellular blue naevus features well-circumscribed nests of lightly pigmented, fusiform to ovoid melanocytes.
- Ancillary: Melanocytes in blue naevi are usually positive for HMB45, SOX10, and melan-A. GNAQ, GNA11, PLCB4, or CYSLTR2 mutations are common in cellular blue naevi.
Reference Gallery:
Dendritic blue naevus. Poorly defined dermal hyperpigmented fibrosing proliferation.
Dendritic blue naevus. There are small spindled and dendritic melanocytes in a fibrotic background.
Blue naevus. This relatively large lesion exemplifies the characteristic colour due to the Tyndall effect of preferential blue colour transmission.
Cellular blue naevus. Symmetrical heavily pigmented nodule elevating the skin without ulceration.
Cellular blue naevus. Biphasic architecture with an upper intradermal, poorly delineated area of dendritic blue naevus and deep expansion pushing away the subcutis, with cellular nests of unpigmented melanocytes.
Cellular blue naevus. Higher magnification shows cellular nests of medium-sized fusiform to ovoid cells surrounded by heavily pigmented spindle cells.
Dendritic blue naevus. Poorly defined, hyperpigmented, fibrosing dermal proliferation.
Dendritic blue naevus. Small, poorly defined, spindled and dendritic dermal melanocytes.
Dendritic blue naevus. Higher magnification shows small spindled and dendritic melanocytes in a fasciculated fibrotic background.
Cellular blue naevus. Poorly delineated, spindled and fibrotic intradermal proliferation expanding deeply into the subcutis, with central myxoid/cystic changes surrounding cellular nests.
Cellular blue naevus. High-magnification view of the central area with myxoid/cystic changes surrounding cellular nests of bland, spindled, unpigmented melanocytes.
Plaque-type cellular blue naevus. Biphasic architecture, with a poorly delineated upper intradermal area of dendritic blue naevus and deep expansion extending into the subcutis with cellular nests of non-pigmented melanocytes.

Q: The diagnosis of a [...] is established when histopathology reveals a common compound or dermal nevus that harbors a deep nodular subpopulation (clone) of morphologically distinct melanocytes.
Combined naevus. Deep dermal nodular melanocytic proliferation (clone) within a common compound naevus (haematoxylin phloxine saffron stain).
Combined naevus. Dermal clone composed of large spindled and epithelioid melanocytes (haematoxylin phloxine saffron stain).
A: Combined Naevus
Back Extra: Combined Naevus
- Clinical: Patients with combined naevus commonly present with a papule or nodule in a patch or plaque with different pigmentation, and there can be a history of recent change.
- Micro: Typically, a compound or dermal naevus of the superficial congenital type with a subpopulation of morphologically distinct cells, usually situated in the superficial dermis.
- Ancillary: Immunohistochemistry or molecular studies can assist in ruling out BAP1-inactivated, WNT-activated, and pigmented epithelioid melanocytoma, as well as proliferative nodules in congenital naevi.
Reference Gallery:
Combined naevus. Deep dermal nodular melanocytic proliferation (clone) within a common compound naevus (haematoxylin phloxine saffron stain).
Combined naevus. Dermal clone composed of large spindled and epithelioid melanocytes (haematoxylin phloxine saffron stain).

Q: In a Combined Naevus, the distinct subpopulation of melanocytes (often large spindled and epithelioid cells) forming a nodule within the background common nevus is termed a dermal [...].
Combined naevus. Deep dermal nodular melanocytic proliferation (clone) within a common compound naevus (haematoxylin phloxine saffron stain).
Combined naevus. Dermal clone composed of large spindled and epithelioid melanocytes (haematoxylin phloxine saffron stain).
A: clone
Back Extra: Combined Naevus
- Clinical: Patients with combined naevus commonly present with a papule or nodule in a patch or plaque with different pigmentation, and there can be a history of recent change.
- Micro: Typically, a compound or dermal naevus of the superficial congenital type with a subpopulation of morphologically distinct cells, usually situated in the superficial dermis.
- Ancillary: Immunohistochemistry or molecular studies can assist in ruling out BAP1-inactivated, WNT-activated, and pigmented epithelioid melanocytoma, as well as proliferative nodules in congenital naevi.
Reference Gallery:
Combined naevus. Deep dermal nodular melanocytic proliferation (clone) within a common compound naevus (haematoxylin phloxine saffron stain).
Combined naevus. Dermal clone composed of large spindled and epithelioid melanocytes (haematoxylin phloxine saffron stain).

Q: Histologically, the hallmark of benign Junctional, Compound, and Dermal Naevi is a progressive pattern of [...] with descent into the dermis, transitioning from superficial epithelioid (type A) cells to intermediate lymphocyte-like (type B) cells, and finally to deep spindled (type C) cells.
Dermal naevus. The naevus is raised, well-circumscribed, and symmetrical, with papillomatous surface configuration. Naevus cells are uniformly dispersed and show diminished cellularity and maturation with depth.
Dermal naevus. Type A naevus cells in the superficial dermis. These cells are also termed “epithelioid” because of the relatively prominent pink cytoplasm and thus resemblance to epithelial cells. The nuclei are small and uniform.
Dermal naevus. Type B naevus cells in the middle portion of the naevus. These cells are also termed “lymphocytoid” because of scant cytoplasm and hence resemblance to lymphocytes.
A: maturation
Back Extra: Junctional, Compound, and Dermal Naevi
- Clinical: Junctional, compound, and dermal naevi are benign, well-circumscribed, symmetrical, and uniformly pigmented macules or papules up to 6 mm in diameter.
- Micro: Naevus cells in dermal naevi show a pattern of maturation from large epithelioid cells (type A) in the superficial dermis to small lymphocyte-like cells (type B) and finally to spindled cells (type C) in the deep dermis.
- Ancillary: DNA copy-number analysis and BRAF p.V600E mutations can assist in distinguishing common acquired naevi from melanoma.
Reference Gallery:
Compound naevus. The naevus is slightly raised, well-defined, and symmetrical, with regular borders and uniform colour. However, a slightly darker peripheral rim suggests designation as a “cockade” naevus.
Dermal naevus. The naevus is raised, well-circumscribed, and symmetrical, with papillomatous surface configuration. Naevus cells are uniformly dispersed and show diminished cellularity and maturation with depth.
Dermal naevus. Type A naevus cells in the superficial dermis. These cells are also termed “epithelioid” because of the relatively prominent pink cytoplasm and thus resemblance to epithelial cells. The nuclei are small and uniform.
Dermal naevus. Type B naevus cells in the middle portion of the naevus. These cells are also termed “lymphocytoid” because of scant cytoplasm and hence resemblance to lymphocytes.
Dermal naevus. Type C naevus cells seen in the deepest portion of the naevus and the final stage of maturation (or senescence) with depth in a naevus. These cells are variably spindled with slight Schwannian differentiation and dispersed in a delicate matrix. These changes are often termed “neurotization”.
Compound naevus. Dermoscopic features. Cobblestone pattern with uniform dark-brown colour.
Compound naevus. Clinical features.
Dermal naevus. Dermoscopic features. Uniform, slightly pinkish tan skin colour, ectatic vascular channels.
Dermal naevus. Clinical features.
Junctional naevus. Clinical features.
Junctional naevus. Dermoscopic features. Uniform dark-brown colour with network at periphery and slight radial streaming.
Compound melanocytic naevus. A well-circumscribed, symmetrical, moderately cellular proliferation of naevoid melanocytes, with expansion of the papillary dermis. There is no adjacent junctional component (shoulder).

Q: In the deepest portions of Junctional, Compound, and Dermal Naevi, the melanocytes terminally differentiate into spindled type C cells with slight Schwannian differentiation dispersed in a delicate matrix, a benign histologic change specifically termed [...].
Dermal naevus. Type C naevus cells seen in the deepest portion of the naevus and the final stage of maturation (or senescence) with depth in a naevus. These cells are variably spindled with slight Schwannian differentiation and dispersed in a delicate matrix. These changes are often termed “neurotization”.
A: neurotization
Back Extra: Junctional, Compound, and Dermal Naevi
- Clinical: Junctional, compound, and dermal naevi are benign, well-circumscribed, symmetrical, and uniformly pigmented macules or papules up to 6 mm in diameter.
- Micro: Naevus cells in dermal naevi show a pattern of maturation from large epithelioid cells (type A) in the superficial dermis to small lymphocyte-like cells (type B) and finally to spindled cells (type C) in the deep dermis.
- Ancillary: DNA copy-number analysis and BRAF p.V600E mutations can assist in distinguishing common acquired naevi from melanoma.
Reference Gallery:
Compound naevus. The naevus is slightly raised, well-defined, and symmetrical, with regular borders and uniform colour. However, a slightly darker peripheral rim suggests designation as a “cockade” naevus.
Dermal naevus. The naevus is raised, well-circumscribed, and symmetrical, with papillomatous surface configuration. Naevus cells are uniformly dispersed and show diminished cellularity and maturation with depth.
Dermal naevus. Type A naevus cells in the superficial dermis. These cells are also termed “epithelioid” because of the relatively prominent pink cytoplasm and thus resemblance to epithelial cells. The nuclei are small and uniform.
Dermal naevus. Type B naevus cells in the middle portion of the naevus. These cells are also termed “lymphocytoid” because of scant cytoplasm and hence resemblance to lymphocytes.
Dermal naevus. Type C naevus cells seen in the deepest portion of the naevus and the final stage of maturation (or senescence) with depth in a naevus. These cells are variably spindled with slight Schwannian differentiation and dispersed in a delicate matrix. These changes are often termed “neurotization”.
Compound naevus. Dermoscopic features. Cobblestone pattern with uniform dark-brown colour.
Compound naevus. Clinical features.
Dermal naevus. Dermoscopic features. Uniform, slightly pinkish tan skin colour, ectatic vascular channels.
Dermal naevus. Clinical features.
Junctional naevus. Clinical features.
Junctional naevus. Dermoscopic features. Uniform dark-brown colour with network at periphery and slight radial streaming.
Compound melanocytic naevus. A well-circumscribed, symmetrical, moderately cellular proliferation of naevoid melanocytes, with expansion of the papillary dermis. There is no adjacent junctional component (shoulder).

Q: Well-circumscribed, highly symmetrical pigmented macules or papules with a uniform color (typically < 6 mm in diameter) that show a cobblestone or uniform network pattern on dermoscopy clinically represent benign [...].
Compound naevus. Dermoscopic features. Cobblestone pattern with uniform dark-brown colour.
Compound naevus. Clinical features.
Junctional naevus. Dermoscopic features. Uniform dark-brown colour with network at periphery and slight radial streaming.
A: Junctional, Compound, and Dermal Naevi
Back Extra: Junctional, Compound, and Dermal Naevi
- Clinical: Junctional, compound, and dermal naevi are benign, well-circumscribed, symmetrical, and uniformly pigmented macules or papules up to 6 mm in diameter.
- Micro: Naevus cells in dermal naevi show a pattern of maturation from large epithelioid cells (type A) in the superficial dermis to small lymphocyte-like cells (type B) and finally to spindled cells (type C) in the deep dermis.
- Ancillary: DNA copy-number analysis and BRAF p.V600E mutations can assist in distinguishing common acquired naevi from melanoma.
Reference Gallery:
Compound naevus. The naevus is slightly raised, well-defined, and symmetrical, with regular borders and uniform colour. However, a slightly darker peripheral rim suggests designation as a “cockade” naevus.
Dermal naevus. The naevus is raised, well-circumscribed, and symmetrical, with papillomatous surface configuration. Naevus cells are uniformly dispersed and show diminished cellularity and maturation with depth.
Dermal naevus. Type A naevus cells in the superficial dermis. These cells are also termed “epithelioid” because of the relatively prominent pink cytoplasm and thus resemblance to epithelial cells. The nuclei are small and uniform.
Dermal naevus. Type B naevus cells in the middle portion of the naevus. These cells are also termed “lymphocytoid” because of scant cytoplasm and hence resemblance to lymphocytes.
Dermal naevus. Type C naevus cells seen in the deepest portion of the naevus and the final stage of maturation (or senescence) with depth in a naevus. These cells are variably spindled with slight Schwannian differentiation and dispersed in a delicate matrix. These changes are often termed “neurotization”.
Compound naevus. Dermoscopic features. Cobblestone pattern with uniform dark-brown colour.
Compound naevus. Clinical features.
Dermal naevus. Dermoscopic features. Uniform, slightly pinkish tan skin colour, ectatic vascular channels.
Dermal naevus. Clinical features.
Junctional naevus. Clinical features.
Junctional naevus. Dermoscopic features. Uniform dark-brown colour with network at periphery and slight radial streaming.
Compound melanocytic naevus. A well-circumscribed, symmetrical, moderately cellular proliferation of naevoid melanocytes, with expansion of the papillary dermis. There is no adjacent junctional component (shoulder).

Q: Extremely large Congenital Melanocytic Nevi that cover massive areas of the body are classically termed [...], which carry an increased risk of malignant transformation.
Giant congenital naevus. This pigmented lesion, which was present at birth, covers a large area of skin. Such lesions are sometimes known as “garment naevi”. Note a smaller so-called “satellite” lesion on the thigh.
A: garment nevi
Back Extra: Congenital Melanocytic Nevi
- Clinical: Congenital melanocytic nevi are typically categorized as small, intermediate, or giant based on their size, with the risk of melanoma increasing with larger nevi.
- Micro: Congenital melanocytic nevi often show a distinct pattern of cells, from large epithelioid type A cells in the upper dermis to small lymphocyte-like type B cells and spindled type C cells in the deeper dermis.
- Ancillary: NRAS mutations are present in the majority of large congenital melanocytic nevi, while BRAF p.V600E mutations are less common.
Reference Gallery:
Congenital melanocytic naevus. A broad plaque lesion, which in this instance is generally uniformly pigmented brown. This lesion is intermediate in terms of size.
Giant congenital naevus. This pigmented lesion, which was present at birth, covers a large area of skin. Such lesions are sometimes known as “garment naevi”. Note a smaller so-called “satellite” lesion on the thigh.
Congenital naevus. Note the depth of the dermal component and the concentration of cells around skin adnexa.
Congenital naevus, small type. Dome-shaped lesion composed mostly of dark lymphocyte-like type-B cells (upper part of lesion) and pale-staining spindle cells (lower part of lesion).
Congenital naevus, small type. Greater detail of naevus with lymphocyte-like type-B cells and spindled type-C cells. The type-C cells mimic neural structures, exhibiting Schwannian differentiation.
Congenital melanocytic naevus with junctional atypia. A congenital melanocytic naevus is present in the dermis and at the junction.
Congenital melanocytic naevus with junctional atypia. In the uppermost part of the lesion, cells are homogeneous and typical.
Congenital melanocytic naevus. Symmetrical, oval, brown, well-circumscribed plaque with prominent terminal hairs.
Congenital melanocytic naevus. Dermoscopic features showing haloed and target globules and blotches.

Q: Histologically, Congenital Melanocytic Nevi exhibit a distinct maturation pattern progressing from superficial epithelioid cells (type A), to intermediate lymphocyte-like cells (type B), and finally to deep, spindled [...] cells.
Congenital naevus, small type. Dome-shaped lesion composed mostly of dark lymphocyte-like type-B cells (upper part of lesion) and pale-staining spindle cells (lower part of lesion).
Congenital naevus, small type. Greater detail of naevus with lymphocyte-like type-B cells and spindled type-C cells. The type-C cells mimic neural structures, exhibiting Schwannian differentiation.
A: type C
Back Extra: Congenital Melanocytic Nevi
- Clinical: Congenital melanocytic nevi are typically categorized as small, intermediate, or giant based on their size, with the risk of melanoma increasing with larger nevi.
- Micro: Congenital melanocytic nevi often show a distinct pattern of cells, from large epithelioid type A cells in the upper dermis to small lymphocyte-like type B cells and spindled type C cells in the deeper dermis.
- Ancillary: NRAS mutations are present in the majority of large congenital melanocytic nevi, while BRAF p.V600E mutations are less common.
Reference Gallery:
Congenital melanocytic naevus. A broad plaque lesion, which in this instance is generally uniformly pigmented brown. This lesion is intermediate in terms of size.
Giant congenital naevus. This pigmented lesion, which was present at birth, covers a large area of skin. Such lesions are sometimes known as “garment naevi”. Note a smaller so-called “satellite” lesion on the thigh.
Congenital naevus. Note the depth of the dermal component and the concentration of cells around skin adnexa.
Congenital naevus, small type. Dome-shaped lesion composed mostly of dark lymphocyte-like type-B cells (upper part of lesion) and pale-staining spindle cells (lower part of lesion).
Congenital naevus, small type. Greater detail of naevus with lymphocyte-like type-B cells and spindled type-C cells. The type-C cells mimic neural structures, exhibiting Schwannian differentiation.
Congenital melanocytic naevus with junctional atypia. A congenital melanocytic naevus is present in the dermis and at the junction.
Congenital melanocytic naevus with junctional atypia. In the uppermost part of the lesion, cells are homogeneous and typical.
Congenital melanocytic naevus. Symmetrical, oval, brown, well-circumscribed plaque with prominent terminal hairs.
Congenital melanocytic naevus. Dermoscopic features showing haloed and target globules and blotches.

Q: A classic microscopic hallmark of Congenital Melanocytic Nevi is the deep extension of melanocytes into the lower dermis with a prominent concentration of cells tracking around [...] (e.g., hair follicles and sweat glands).
Congenital naevus. Note the depth of the dermal component and the concentration of cells around skin adnexa.
Congenital melanocytic naevus. Symmetrical, oval, brown, well-circumscribed plaque with prominent terminal hairs.
A: skin adnexa
Back Extra: Congenital Melanocytic Nevi
- Clinical: Congenital melanocytic nevi are typically categorized as small, intermediate, or giant based on their size, with the risk of melanoma increasing with larger nevi.
- Micro: Congenital melanocytic nevi often show a distinct pattern of cells, from large epithelioid type A cells in the upper dermis to small lymphocyte-like type B cells and spindled type C cells in the deeper dermis.
- Ancillary: NRAS mutations are present in the majority of large congenital melanocytic nevi, while BRAF p.V600E mutations are less common.
Reference Gallery:
Congenital melanocytic naevus. A broad plaque lesion, which in this instance is generally uniformly pigmented brown. This lesion is intermediate in terms of size.
Giant congenital naevus. This pigmented lesion, which was present at birth, covers a large area of skin. Such lesions are sometimes known as “garment naevi”. Note a smaller so-called “satellite” lesion on the thigh.
Congenital naevus. Note the depth of the dermal component and the concentration of cells around skin adnexa.
Congenital naevus, small type. Dome-shaped lesion composed mostly of dark lymphocyte-like type-B cells (upper part of lesion) and pale-staining spindle cells (lower part of lesion).
Congenital naevus, small type. Greater detail of naevus with lymphocyte-like type-B cells and spindled type-C cells. The type-C cells mimic neural structures, exhibiting Schwannian differentiation.
Congenital melanocytic naevus with junctional atypia. A congenital melanocytic naevus is present in the dermis and at the junction.
Congenital melanocytic naevus with junctional atypia. In the uppermost part of the lesion, cells are homogeneous and typical.
Congenital melanocytic naevus. Symmetrical, oval, brown, well-circumscribed plaque with prominent terminal hairs.
Congenital melanocytic naevus. Dermoscopic features showing haloed and target globules and blotches.

Q: A highly characteristic feature of a compound Conjunctival Naevus is the presence of multiple small [...], which can be identified both histologically and clinically on slit-lamp examination.
Conjunctival melanocytic naevus. A compound naevus associated with prominent epithelial inclusion cysts. The lesion shows maturation with depth.
Compound conjunctival naevus. An example of a compound naevus with prominent nests of naevus cells and occasional epithelial cysts in the substantia propria.
A: epithelial inclusion cysts
Back Extra: Conjunctival Naevus
- Clinical: Conjunctival naevi are well-defined, variably pigmented (tan to brown) or amelanotic, mobile macules, papules, or plaques. Compound naevi often show multiple small epithelial inclusion microcysts by slit-lamp examination.
- Micro: Junctional melanocytic naevi exhibit an intraepithelial proliferation of round to oval epithelioid cells. Compound naevi contain naevus cells within the epithelium and stroma, showing maturation with depth. Subepithelial naevi arise in the stroma, with melanocytes arranged as nests, often amelanotic or minimally pigmented.
- Ancillary: Most conjunctival naevi are positive for HMB45 in the superficial areas and show homogeneous deeper staining for melan-A, SOX10, and MITF. They are usually negative for cyclin D1 and PRAME.
Reference Gallery:
Conjunctival melanocytic naevus. A compound naevus associated with prominent epithelial inclusion cysts. The lesion shows maturation with depth.
Compound conjunctival melanocytic naevus. In the context of a thin conjunctival epithelium, junctional melanocytic nests appear to be confluent and show consumption of the epidermis. Such a pattern is common in conjunctival naevi and does not indicate atypia.
Conjunctival compound naevus. A variably pigmented, well-circumscribed lesion.
Conjunctival junctional naevus. Junctional nests in a naevus from a teenaged patient.
Compound conjunctival naevus. An example of a compound naevus with prominent nests of naevus cells and occasional epithelial cysts in the substantia propria.
Conjunctival subepithelial naevus. An example of a subepithelial conjunctival melanocytic naevus with mature naevus cells in the stroma.

Q: In a compound Conjunctival Naevus, melanocytic nests are present in both the epithelium and the stroma, characteristically exhibiting [...] with increasing depth.
Conjunctival melanocytic naevus. A compound naevus associated with prominent epithelial inclusion cysts. The lesion shows maturation with depth.
A: maturation
Back Extra: Conjunctival Naevus
- Clinical: Conjunctival naevi are well-defined, variably pigmented (tan to brown) or amelanotic, mobile macules, papules, or plaques. Compound naevi often show multiple small epithelial inclusion microcysts by slit-lamp examination.
- Micro: Junctional melanocytic naevi exhibit an intraepithelial proliferation of round to oval epithelioid cells. Compound naevi contain naevus cells within the epithelium and stroma, showing maturation with depth. Subepithelial naevi arise in the stroma, with melanocytes arranged as nests, often amelanotic or minimally pigmented.
- Ancillary: Most conjunctival naevi are positive for HMB45 in the superficial areas and show homogeneous deeper staining for melan-A, SOX10, and MITF. They are usually negative for cyclin D1 and PRAME.
Reference Gallery:
Conjunctival melanocytic naevus. A compound naevus associated with prominent epithelial inclusion cysts. The lesion shows maturation with depth.
Compound conjunctival melanocytic naevus. In the context of a thin conjunctival epithelium, junctional melanocytic nests appear to be confluent and show consumption of the epidermis. Such a pattern is common in conjunctival naevi and does not indicate atypia.
Conjunctival compound naevus. A variably pigmented, well-circumscribed lesion.
Conjunctival junctional naevus. Junctional nests in a naevus from a teenaged patient.
Compound conjunctival naevus. An example of a compound naevus with prominent nests of naevus cells and occasional epithelial cysts in the substantia propria.
Conjunctival subepithelial naevus. An example of a subepithelial conjunctival melanocytic naevus with mature naevus cells in the stroma.

Q: A Conjunctival Naevus that lacks an intraepithelial component and consists exclusively of mature melanocytes arranged as nests within the underlying stroma is classified as a [...] nevus.
Conjunctival subepithelial naevus. An example of a subepithelial conjunctival melanocytic naevus with mature naevus cells in the stroma.
A: subepithelial
Back Extra: Conjunctival Naevus
- Clinical: Conjunctival naevi are well-defined, variably pigmented (tan to brown) or amelanotic, mobile macules, papules, or plaques. Compound naevi often show multiple small epithelial inclusion microcysts by slit-lamp examination.
- Micro: Junctional melanocytic naevi exhibit an intraepithelial proliferation of round to oval epithelioid cells. Compound naevi contain naevus cells within the epithelium and stroma, showing maturation with depth. Subepithelial naevi arise in the stroma, with melanocytes arranged as nests, often amelanotic or minimally pigmented.
- Ancillary: Most conjunctival naevi are positive for HMB45 in the superficial areas and show homogeneous deeper staining for melan-A, SOX10, and MITF. They are usually negative for cyclin D1 and PRAME.
Reference Gallery:
Conjunctival melanocytic naevus. A compound naevus associated with prominent epithelial inclusion cysts. The lesion shows maturation with depth.
Compound conjunctival melanocytic naevus. In the context of a thin conjunctival epithelium, junctional melanocytic nests appear to be confluent and show consumption of the epidermis. Such a pattern is common in conjunctival naevi and does not indicate atypia.
Conjunctival compound naevus. A variably pigmented, well-circumscribed lesion.
Conjunctival junctional naevus. Junctional nests in a naevus from a teenaged patient.
Compound conjunctival naevus. An example of a compound naevus with prominent nests of naevus cells and occasional epithelial cysts in the substantia propria.
Conjunctival subepithelial naevus. An example of a subepithelial conjunctival melanocytic naevus with mature naevus cells in the stroma.

Q: Histologically, the deep penetrating subtype of WNT-activated deep penetrating / plexiform melanocytoma (naevus) characteristically presents as a dermal-based tumor with a [...] (or V-shaped) architecture.
WNT-activated deep penetrating / plexiform melanocytoma (naevus), deep penetrating subtype. V-shaped dermal-based tumour.
A: wedge-shaped
Back Extra: WNT-activated deep penetrating / plexiform melanocytoma (naevus)
- Clinical: WNT-activated deep penetrating / plexiform melanocytoma (naevus) typically presents as a symmetrical, well-circumscribed, darkly pigmented papule < 10 mm in size, often on the head and neck.
- Micro: The tumor is characterized by a dermal-based proliferation of spindled and/or epithelioid melanocytes arranged in a wedge-shaped, fascicular, or plexiform pattern, often with a junctional component.
- Ancillary: β-catenin immunohistochemistry shows nuclear positivity, and molecular analysis reveals mutations in the WNT pathway, primarily CTNNB1, and MAPK pathway mutations such as BRAF (p.V600E).
Reference Gallery:
WNT-activated deep penetrating / plexiform melanocytoma (naevus), plexiform spindle cell pattern. Pigmented and spindled melanocytes are centred on the cutaneous vascular plexus, assuming a plexiform (candelabra-like) architectural configuration.
WNT-activated deep penetrating / plexiform melanocytoma (naevus), deep penetrating subtype. V-shaped dermal-based tumour.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles of melanocytes showing nuclear positivity for β-catenin immunostaining, among conventional naevus melanocytes devoid of nuclear expression.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). β-catenin immunohistochemistry with a red substrate to distinguish positive expression from melanin. Positive nuclear β-catenin highlights a plexiform architecture of the proliferation.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Slightly enlarged fusiform melanocytes are arranged in bundles. These melanocytes contain scant, finely granular, greyish-brown cytoplasmic melanin, as well as enlarged nuclei with slight pleomorphism (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus), plexiform spindle cell subtype. Fascicles of melanocytes with scattered melanophages infiltrate the deep dermis (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus), plexiform spindle cell subtype. Fascicles of melanocytes can extend along adnexal structures (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles with slightly enlarged melanocytes with little pleomorphism are present among sheets of bland cells of a conventional dermal naevus, separated by scattered melanophages (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles of melanocytes are present among sheets of a conventional dermal naevus (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus). β-catenin immunohistochemistry with a red substrate to distinguish positive expression from melanin. The melanocytes show a cytoplasmic and nuclear staining. Internal control is represented by a hair follicle without nuclear staining.
WNT-activated deep penetrating / plexiform melanocytoma (naevus), deep penetrating subtype. Slightly enlarged melanocytes are arranged in fascicles or bundles, associated with some melanophages. The melanocytes have a finely granular pigmented cytoplasm and present some degree of atypia.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). A pigmented nodule that is generally symmetrical and not ulcerated. Biopsy and histopathological examination are required to distinguish this lesion from a nodular melanoma.

Q: A hallmark immunohistochemical finding in WNT-activated deep penetrating / plexiform melanocytoma (naevus) is strong nuclear expression of [...], which highlights the proliferating fascicles and distinguishes them from conventional nevus cells.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles of melanocytes showing nuclear positivity for β-catenin immunostaining, among conventional naevus melanocytes devoid of nuclear expression.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). β-catenin immunohistochemistry with a red substrate to distinguish positive expression from melanin. Positive nuclear β-catenin highlights a plexiform architecture of the proliferation.
A: β-catenin
Back Extra: WNT-activated deep penetrating / plexiform melanocytoma (naevus)
- Clinical: WNT-activated deep penetrating / plexiform melanocytoma (naevus) typically presents as a symmetrical, well-circumscribed, darkly pigmented papule < 10 mm in size, often on the head and neck.
- Micro: The tumor is characterized by a dermal-based proliferation of spindled and/or epithelioid melanocytes arranged in a wedge-shaped, fascicular, or plexiform pattern, often with a junctional component.
- Ancillary: β-catenin immunohistochemistry shows nuclear positivity, and molecular analysis reveals mutations in the WNT pathway, primarily CTNNB1, and MAPK pathway mutations such as BRAF (p.V600E).
Reference Gallery:
WNT-activated deep penetrating / plexiform melanocytoma (naevus), plexiform spindle cell pattern. Pigmented and spindled melanocytes are centred on the cutaneous vascular plexus, assuming a plexiform (candelabra-like) architectural configuration.
WNT-activated deep penetrating / plexiform melanocytoma (naevus), deep penetrating subtype. V-shaped dermal-based tumour.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles of melanocytes showing nuclear positivity for β-catenin immunostaining, among conventional naevus melanocytes devoid of nuclear expression.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). β-catenin immunohistochemistry with a red substrate to distinguish positive expression from melanin. Positive nuclear β-catenin highlights a plexiform architecture of the proliferation.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Slightly enlarged fusiform melanocytes are arranged in bundles. These melanocytes contain scant, finely granular, greyish-brown cytoplasmic melanin, as well as enlarged nuclei with slight pleomorphism (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus), plexiform spindle cell subtype. Fascicles of melanocytes with scattered melanophages infiltrate the deep dermis (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus), plexiform spindle cell subtype. Fascicles of melanocytes can extend along adnexal structures (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles with slightly enlarged melanocytes with little pleomorphism are present among sheets of bland cells of a conventional dermal naevus, separated by scattered melanophages (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles of melanocytes are present among sheets of a conventional dermal naevus (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus). β-catenin immunohistochemistry with a red substrate to distinguish positive expression from melanin. The melanocytes show a cytoplasmic and nuclear staining. Internal control is represented by a hair follicle without nuclear staining.
WNT-activated deep penetrating / plexiform melanocytoma (naevus), deep penetrating subtype. Slightly enlarged melanocytes are arranged in fascicles or bundles, associated with some melanophages. The melanocytes have a finely granular pigmented cytoplasm and present some degree of atypia.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). A pigmented nodule that is generally symmetrical and not ulcerated. Biopsy and histopathological examination are required to distinguish this lesion from a nodular melanoma.

Q: Clinically, WNT-activated deep penetrating / plexiform melanocytoma (naevus) often presents as a heavily pigmented, symmetrical nodule that requires biopsy and histopathologic evaluation to definitively rule out [...].
WNT-activated deep penetrating / plexiform melanocytoma (naevus). A pigmented nodule that is generally symmetrical and not ulcerated. Biopsy and histopathological examination are required to distinguish this lesion from a nodular melanoma.
A: nodular melanoma
Back Extra: WNT-activated deep penetrating / plexiform melanocytoma (naevus)
- Clinical: WNT-activated deep penetrating / plexiform melanocytoma (naevus) typically presents as a symmetrical, well-circumscribed, darkly pigmented papule < 10 mm in size, often on the head and neck.
- Micro: The tumor is characterized by a dermal-based proliferation of spindled and/or epithelioid melanocytes arranged in a wedge-shaped, fascicular, or plexiform pattern, often with a junctional component.
- Ancillary: β-catenin immunohistochemistry shows nuclear positivity, and molecular analysis reveals mutations in the WNT pathway, primarily CTNNB1, and MAPK pathway mutations such as BRAF (p.V600E).
Reference Gallery:
WNT-activated deep penetrating / plexiform melanocytoma (naevus), plexiform spindle cell pattern. Pigmented and spindled melanocytes are centred on the cutaneous vascular plexus, assuming a plexiform (candelabra-like) architectural configuration.
WNT-activated deep penetrating / plexiform melanocytoma (naevus), deep penetrating subtype. V-shaped dermal-based tumour.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles of melanocytes showing nuclear positivity for β-catenin immunostaining, among conventional naevus melanocytes devoid of nuclear expression.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). β-catenin immunohistochemistry with a red substrate to distinguish positive expression from melanin. Positive nuclear β-catenin highlights a plexiform architecture of the proliferation.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Slightly enlarged fusiform melanocytes are arranged in bundles. These melanocytes contain scant, finely granular, greyish-brown cytoplasmic melanin, as well as enlarged nuclei with slight pleomorphism (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus), plexiform spindle cell subtype. Fascicles of melanocytes with scattered melanophages infiltrate the deep dermis (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus), plexiform spindle cell subtype. Fascicles of melanocytes can extend along adnexal structures (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles with slightly enlarged melanocytes with little pleomorphism are present among sheets of bland cells of a conventional dermal naevus, separated by scattered melanophages (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus). Bundles of melanocytes are present among sheets of a conventional dermal naevus (haematoxylin phloxine saffron stain).
WNT-activated deep penetrating / plexiform melanocytoma (naevus). β-catenin immunohistochemistry with a red substrate to distinguish positive expression from melanin. The melanocytes show a cytoplasmic and nuclear staining. Internal control is represented by a hair follicle without nuclear staining.
WNT-activated deep penetrating / plexiform melanocytoma (naevus), deep penetrating subtype. Slightly enlarged melanocytes are arranged in fascicles or bundles, associated with some melanophages. The melanocytes have a finely granular pigmented cytoplasm and present some degree of atypia.
WNT-activated deep penetrating / plexiform melanocytoma (naevus). A pigmented nodule that is generally symmetrical and not ulcerated. Biopsy and histopathological examination are required to distinguish this lesion from a nodular melanoma.

Q: Clinically, [...] typically presents as a bluish or darker patch classically located on the lower back and buttocks, which often fades or disappears by the age of 5–6 years.
Congenital dermal melanocytosis. Variably sized bluish patches on the buttocks, back, and arms.
A: Congenital Dermal Melanocytosis
Back Extra: Congenital Dermal Melanocytosis
- Clinical: Congenital dermal melanocytosis (CDM) typically appears as a bluish or darker patch on the lower back and buttocks, and often disappears by the age of 5–6 years.
- Micro: Histologically, CDM is characterized by pigmented dendritic melanocytes sparsely dispersed in the dermis, often parallel to the epidermis.
- Ancillary: GNAQ and GNA11 mutations have been identified in cases associated with phakomatosis pigmentovascularis, but routine molecular testing is not clinically relevant.
Reference Gallery:
Congenital dermal melanocytosis. Variably sized bluish patches on the buttocks, back, and arms.
Phakomatosis pigmentovascularis. Aberrant congenital dermal melanocytosis on the trunk and extremities coexists with naevus flammeus on the left chest and arm.
Congenital dermal melanocytosis. Pigmented dendritic melanocytes are scattered in the dermis.

Q: Histologically, Congenital Dermal Melanocytosis is characterized by sparsely dispersed [...] in the dermis, often oriented parallel to the epidermis.
Congenital dermal melanocytosis. Pigmented dendritic melanocytes are scattered in the dermis.
A: pigmented dendritic melanocytes
Back Extra: Congenital Dermal Melanocytosis
- Clinical: Congenital dermal melanocytosis (CDM) typically appears as a bluish or darker patch on the lower back and buttocks, and often disappears by the age of 5–6 years.
- Micro: Histologically, CDM is characterized by pigmented dendritic melanocytes sparsely dispersed in the dermis, often parallel to the epidermis.
- Ancillary: GNAQ and GNA11 mutations have been identified in cases associated with phakomatosis pigmentovascularis, but routine molecular testing is not clinically relevant.
Reference Gallery:
Congenital dermal melanocytosis. Variably sized bluish patches on the buttocks, back, and arms.
Phakomatosis pigmentovascularis. Aberrant congenital dermal melanocytosis on the trunk and extremities coexists with naevus flammeus on the left chest and arm.
Congenital dermal melanocytosis. Pigmented dendritic melanocytes are scattered in the dermis.

Q: Aberrant Congenital Dermal Melanocytosis on the trunk and extremities coexisting with a nevus flammeus (port-wine stain) is characteristic of [...], a condition occasionally associated with GNAQ and GNA11 mutations.
Phakomatosis pigmentovascularis. Aberrant congenital dermal melanocytosis on the trunk and extremities coexists with naevus flammeus on the left chest and arm.
A: phakomatosis pigmentovascularis
Back Extra: Congenital Dermal Melanocytosis
- Clinical: Congenital dermal melanocytosis (CDM) typically appears as a bluish or darker patch on the lower back and buttocks, and often disappears by the age of 5–6 years.
- Micro: Histologically, CDM is characterized by pigmented dendritic melanocytes sparsely dispersed in the dermis, often parallel to the epidermis.
- Ancillary: GNAQ and GNA11 mutations have been identified in cases associated with phakomatosis pigmentovascularis, but routine molecular testing is not clinically relevant.
Reference Gallery:
Congenital dermal melanocytosis. Variably sized bluish patches on the buttocks, back, and arms.
Phakomatosis pigmentovascularis. Aberrant congenital dermal melanocytosis on the trunk and extremities coexists with naevus flammeus on the left chest and arm.
Congenital dermal melanocytosis. Pigmented dendritic melanocytes are scattered in the dermis.

Q: Clinically, a Dysplastic Nevus often presents with an uneven contour, color variegation, and a raised center with a flat periphery, resembling a [...] appearance.
Dysplastic nevus. This lesion is broad, somewhat irregular, raised in the center, and flat at the periphery. It has variegated shades of tan and dark brown, and an indefinite border.
A: fried egg
Back Extra: Dysplastic Nevus
- Clinical: Dysplastic nevi typically present as macules or papules with a non-well-defined border, color variegation, and an uneven peripheral contour. They often have a raised center, resembling a fried egg or target appearance.
- Micro: Melanocytic dysplasia is characterized by architectural disorder, including junctional shoulders, bridging of nests, and cytological atypia with enlarged nuclei and irregular hyperchromatic nuclei.
- Ancillary: Immunohistochemistry is not typically necessary, but when used, dysplastic nevi label with S100, melan-A, MITF, tyrosinase, and SOX10. The Ki-67 proliferation index is typically < 5%.
Reference Gallery:
Dysplastic nevus, low grade. Cytological atypia. Lesional melanocytes have nuclei that are enlarged but in general less than 1.5 times the size of the nucleus of a resting basal keratinocyte. There is also relatively abundant cytoplasm, as well as “dusty” melanin pigment.
Dysplastic nevus, high grade. Cytological atypia. There are several cells in this field that have nuclei larger than 1.5 times that of a resting basal keratinocyte. In addition, they have variably abundant cytoplasm and “dusty” melanin pigment.
Dysplastic nevus. This lesion is broad, somewhat irregular, raised in the center, and flat at the periphery. It has variegated shades of tan and dark brown, and an indefinite border.
Compound dysplastic nevus, low grade. A broad lesion characterized by relative symmetry and uniformly elongated rete ridges. In the center, a dermal component partly fills the expanded papillary dermis; at the periphery, there are junctional shoulders. There is a patchy perivascular lymphocytic infiltrate.
Compound dysplastic nevus, low grade. High-power view of the edge of the dermal component and the beginning of the adjacent shoulder. The junctional component is moderately cellular and is composed of naevoid to epithelioid melanocytes; the nuclear size of these cells is less than 1.5 times that of resting (i.e. with the smallest nuclei) basal keratinocytes, constituting moderate random cytological atypia.
Compound dysplastic nevus, high grade. A broad lesion, slightly > 4 mm in diameter on the slide, with changes present at the left specimen edge. The rete ridges are somewhat irregularly thickened, although relatively uniformly elongated. There is a patchy to focally more dense lymphocytic infiltrate in the dermis, mostly perivascular and partly interstitial. Nests of melanocytes can be seen near the tips and sides of rete ridges, with some bridging nests.
Compound dysplastic nevus, high grade. Some of the lesional melanocytes have a nuclear size more than 1.5 times that of resting basal keratinocytes, as well as irregular hyperchromatic nuclei, constituting severe random cytological atypia. There is a focal tendency to confluence of lesional cell nests in the epidermis, with only minimal evidence of upward scatter in this field. In the dermis, there are perivascular lymphocytes and melanophages, with subtle concentric fibroplasia at the tip of some rete.
Compound dysplastic nevus, high grade. In this focal area of the lesion, there are changes that raise concern for evolving melanoma (at least in situ); there are large cells, and there is a focal tendency to upward pagetoid scatter near the middle of the lesion, not beyond the mid-spinous layer. A few cells in the dermis (left of center) resemble those in the epidermis, with an associated focus of diffuse fibroplasia. The lymphocytic infiltrate is focally band-like; there is well-developed eosinophilic fibroplasia around rete ridges on the right.
Dysplastic nevus. Dermoscopic features. Atypical nevus dermoscopically showing asymmetry of colors and structures. The nevus was diagnosed as a moderately dysplastic compound nevus.
Dysplastic nevus. Dermoscopic features. Large atypical nevus in a fair skin type dermoscopically showing slight asymmetry due to a patchy light-brown network at the periphery and areas of erythema and hypopigmentation in the center. Histologically it was diagnosed as a moderately dysplastic nevus.

Q: A key architectural feature of a compound Dysplastic Nevus is the lateral extension of the junctional melanocytic component beyond the central dermal component, creating what are known as [...].
Compound dysplastic nevus, low grade. A broad lesion characterized by relative symmetry and uniformly elongated rete ridges. In the center, a dermal component partly fills the expanded papillary dermis; at the periphery, there are junctional shoulders. There is a patchy perivascular lymphocytic infiltrate.
Compound dysplastic nevus, low grade. High-power view of the edge of the dermal component and the beginning of the adjacent shoulder. The junctional component is moderately cellular and is composed of naevoid to epithelioid melanocytes; the nuclear size of these cells is less than 1.5 times that of resting (i.e. with the smallest nuclei) basal keratinocytes, constituting moderate random cytological atypia.
A: junctional shoulders
Back Extra: Dysplastic Nevus
- Clinical: Dysplastic nevi typically present as macules or papules with a non-well-defined border, color variegation, and an uneven peripheral contour. They often have a raised center, resembling a fried egg or target appearance.
- Micro: Melanocytic dysplasia is characterized by architectural disorder, including junctional shoulders, bridging of nests, and cytological atypia with enlarged nuclei and irregular hyperchromatic nuclei.
- Ancillary: Immunohistochemistry is not typically necessary, but when used, dysplastic nevi label with S100, melan-A, MITF, tyrosinase, and SOX10. The Ki-67 proliferation index is typically < 5%.
Reference Gallery:
Dysplastic nevus, low grade. Cytological atypia. Lesional melanocytes have nuclei that are enlarged but in general less than 1.5 times the size of the nucleus of a resting basal keratinocyte. There is also relatively abundant cytoplasm, as well as “dusty” melanin pigment.
Dysplastic nevus, high grade. Cytological atypia. There are several cells in this field that have nuclei larger than 1.5 times that of a resting basal keratinocyte. In addition, they have variably abundant cytoplasm and “dusty” melanin pigment.
Dysplastic nevus. This lesion is broad, somewhat irregular, raised in the center, and flat at the periphery. It has variegated shades of tan and dark brown, and an indefinite border.
Compound dysplastic nevus, low grade. A broad lesion characterized by relative symmetry and uniformly elongated rete ridges. In the center, a dermal component partly fills the expanded papillary dermis; at the periphery, there are junctional shoulders. There is a patchy perivascular lymphocytic infiltrate.
Compound dysplastic nevus, low grade. High-power view of the edge of the dermal component and the beginning of the adjacent shoulder. The junctional component is moderately cellular and is composed of naevoid to epithelioid melanocytes; the nuclear size of these cells is less than 1.5 times that of resting (i.e. with the smallest nuclei) basal keratinocytes, constituting moderate random cytological atypia.
Compound dysplastic nevus, high grade. A broad lesion, slightly > 4 mm in diameter on the slide, with changes present at the left specimen edge. The rete ridges are somewhat irregularly thickened, although relatively uniformly elongated. There is a patchy to focally more dense lymphocytic infiltrate in the dermis, mostly perivascular and partly interstitial. Nests of melanocytes can be seen near the tips and sides of rete ridges, with some bridging nests.
Compound dysplastic nevus, high grade. Some of the lesional melanocytes have a nuclear size more than 1.5 times that of resting basal keratinocytes, as well as irregular hyperchromatic nuclei, constituting severe random cytological atypia. There is a focal tendency to confluence of lesional cell nests in the epidermis, with only minimal evidence of upward scatter in this field. In the dermis, there are perivascular lymphocytes and melanophages, with subtle concentric fibroplasia at the tip of some rete.
Compound dysplastic nevus, high grade. In this focal area of the lesion, there are changes that raise concern for evolving melanoma (at least in situ); there are large cells, and there is a focal tendency to upward pagetoid scatter near the middle of the lesion, not beyond the mid-spinous layer. A few cells in the dermis (left of center) resemble those in the epidermis, with an associated focus of diffuse fibroplasia. The lymphocytic infiltrate is focally band-like; there is well-developed eosinophilic fibroplasia around rete ridges on the right.
Dysplastic nevus. Dermoscopic features. Atypical nevus dermoscopically showing asymmetry of colors and structures. The nevus was diagnosed as a moderately dysplastic compound nevus.
Dysplastic nevus. Dermoscopic features. Large atypical nevus in a fair skin type dermoscopically showing slight asymmetry due to a patchy light-brown network at the periphery and areas of erythema and hypopigmentation in the center. Histologically it was diagnosed as a moderately dysplastic nevus.

Q: The cytological atypia in a Dysplastic Nevus is often graded by comparing the size of melanocyte nuclei to those of resting basal keratinocytes; high-grade atypia is defined by melanocytic nuclei that are greater than [...] times the size of a resting basal keratinocyte.
Dysplastic nevus, low grade. Cytological atypia. Lesional melanocytes have nuclei that are enlarged but in general less than 1.5 times the size of the nucleus of a resting basal keratinocyte. There is also relatively abundant cytoplasm, as well as “dusty” melanin pigment.
Dysplastic nevus, high grade. Cytological atypia. There are several cells in this field that have nuclei larger than 1.5 times that of a resting basal keratinocyte. In addition, they have variably abundant cytoplasm and “dusty” melanin pigment.
A: 1.5
Back Extra: Dysplastic Nevus
- Clinical: Dysplastic nevi typically present as macules or papules with a non-well-defined border, color variegation, and an uneven peripheral contour. They often have a raised center, resembling a fried egg or target appearance.
- Micro: Melanocytic dysplasia is characterized by architectural disorder, including junctional shoulders, bridging of nests, and cytological atypia with enlarged nuclei and irregular hyperchromatic nuclei.
- Ancillary: Immunohistochemistry is not typically necessary, but when used, dysplastic nevi label with S100, melan-A, MITF, tyrosinase, and SOX10. The Ki-67 proliferation index is typically < 5%.
Reference Gallery:
Dysplastic nevus, low grade. Cytological atypia. Lesional melanocytes have nuclei that are enlarged but in general less than 1.5 times the size of the nucleus of a resting basal keratinocyte. There is also relatively abundant cytoplasm, as well as “dusty” melanin pigment.
Dysplastic nevus, high grade. Cytological atypia. There are several cells in this field that have nuclei larger than 1.5 times that of a resting basal keratinocyte. In addition, they have variably abundant cytoplasm and “dusty” melanin pigment.
Dysplastic nevus. This lesion is broad, somewhat irregular, raised in the center, and flat at the periphery. It has variegated shades of tan and dark brown, and an indefinite border.
Compound dysplastic nevus, low grade. A broad lesion characterized by relative symmetry and uniformly elongated rete ridges. In the center, a dermal component partly fills the expanded papillary dermis; at the periphery, there are junctional shoulders. There is a patchy perivascular lymphocytic infiltrate.
Compound dysplastic nevus, low grade. High-power view of the edge of the dermal component and the beginning of the adjacent shoulder. The junctional component is moderately cellular and is composed of naevoid to epithelioid melanocytes; the nuclear size of these cells is less than 1.5 times that of resting (i.e. with the smallest nuclei) basal keratinocytes, constituting moderate random cytological atypia.
Compound dysplastic nevus, high grade. A broad lesion, slightly > 4 mm in diameter on the slide, with changes present at the left specimen edge. The rete ridges are somewhat irregularly thickened, although relatively uniformly elongated. There is a patchy to focally more dense lymphocytic infiltrate in the dermis, mostly perivascular and partly interstitial. Nests of melanocytes can be seen near the tips and sides of rete ridges, with some bridging nests.
Compound dysplastic nevus, high grade. Some of the lesional melanocytes have a nuclear size more than 1.5 times that of resting basal keratinocytes, as well as irregular hyperchromatic nuclei, constituting severe random cytological atypia. There is a focal tendency to confluence of lesional cell nests in the epidermis, with only minimal evidence of upward scatter in this field. In the dermis, there are perivascular lymphocytes and melanophages, with subtle concentric fibroplasia at the tip of some rete.
Compound dysplastic nevus, high grade. In this focal area of the lesion, there are changes that raise concern for evolving melanoma (at least in situ); there are large cells, and there is a focal tendency to upward pagetoid scatter near the middle of the lesion, not beyond the mid-spinous layer. A few cells in the dermis (left of center) resemble those in the epidermis, with an associated focus of diffuse fibroplasia. The lymphocytic infiltrate is focally band-like; there is well-developed eosinophilic fibroplasia around rete ridges on the right.
Dysplastic nevus. Dermoscopic features. Atypical nevus dermoscopically showing asymmetry of colors and structures. The nevus was diagnosed as a moderately dysplastic compound nevus.
Dysplastic nevus. Dermoscopic features. Large atypical nevus in a fair skin type dermoscopically showing slight asymmetry due to a patchy light-brown network at the periphery and areas of erythema and hypopigmentation in the center. Histologically it was diagnosed as a moderately dysplastic nevus.

Q: Presenting clinically as uniformly pigmented macules or papules (as seen here), most cases of Genital naevus are driven by a [...] mutation.
Genital naevus. A pigmented plaque-like lesion of the vulva.
Genital naevus. Genital naevus on the glans. Black macule on a 34-year-old man.
A: BRAF p.V600E
Back Extra: Genital naevus
- Clinical: Genital naevi are uniformly pigmented, well-circumscribed, solitary macules or papules, up to 10 mm in size, that typically arise in young adults.
- Micro: The junctional component consists of single cells and nests haphazardly distributed along the epidermal rete ridges, often oriented parallel to the epidermal surface, with focal retraction artefact and dyscohesion.
- Ancillary: Most genital naevi have BRAF p.V600E mutations.
Reference Gallery:
Genital naevus. Deeply pigmented cells extending deeply into the underlying stroma with evidence of cellular maturation.
Genital naevus. High-power view of maturation of cells in the stroma.
Genital naevus. A pigmented plaque-like lesion of the vulva.
Genital naevus. Genital naevus on the glans. Black macule on a 34-year-old man.
Genital naevus. There is a junctional component of single cells and small nests. The cells of the dermal component display mild atypia.
Vulvar naevus. The lesion has a junctional component of nests, with focal retraction artefact and dyscohesion, distributed haphazardly along the epidermal rete ridges; some are oriented parallel to the epidermal surface. The dermal component displays mild cytological atypia superficially but shows maturation with increasing depth.
Vulvar naevus. The lesion has a junctional component of nests, with focal retraction artefact and dyscohesion, distributed haphazardly along the epidermal rete ridges; some are oriented parallel to the epidermal surface. The dermal component displays mild cytological atypia superficially but shows maturation with increasing depth.

Q: A characteristic architectural feature of a Genital naevus is that its junctional nests are often haphazardly distributed and oriented [...] to the epidermal surface, commonly showing focal retraction artifact and dyscohesion.
Vulvar naevus. The lesion has a junctional component of nests, with focal retraction artefact and dyscohesion, distributed haphazardly along the epidermal rete ridges; some are oriented parallel to the epidermal surface. The dermal component displays mild cytological atypia superficially but shows maturation with increasing depth.
Vulvar naevus. The lesion has a junctional component of nests, with focal retraction artefact and dyscohesion, distributed haphazardly along the epidermal rete ridges; some are oriented parallel to the epidermal surface. The dermal component displays mild cytological atypia superficially but shows maturation with increasing depth.
A: parallel
Back Extra: Genital naevus
- Clinical: Genital naevi are uniformly pigmented, well-circumscribed, solitary macules or papules, up to 10 mm in size, that typically arise in young adults.
- Micro: The junctional component consists of single cells and nests haphazardly distributed along the epidermal rete ridges, often oriented parallel to the epidermal surface, with focal retraction artefact and dyscohesion.
- Ancillary: Most genital naevi have BRAF p.V600E mutations.
Reference Gallery:
Genital naevus. Deeply pigmented cells extending deeply into the underlying stroma with evidence of cellular maturation.
Genital naevus. High-power view of maturation of cells in the stroma.
Genital naevus. A pigmented plaque-like lesion of the vulva.
Genital naevus. Genital naevus on the glans. Black macule on a 34-year-old man.
Genital naevus. There is a junctional component of single cells and small nests. The cells of the dermal component display mild atypia.
Vulvar naevus. The lesion has a junctional component of nests, with focal retraction artefact and dyscohesion, distributed haphazardly along the epidermal rete ridges; some are oriented parallel to the epidermal surface. The dermal component displays mild cytological atypia superficially but shows maturation with increasing depth.
Vulvar naevus. The lesion has a junctional component of nests, with focal retraction artefact and dyscohesion, distributed haphazardly along the epidermal rete ridges; some are oriented parallel to the epidermal surface. The dermal component displays mild cytological atypia superficially but shows maturation with increasing depth.

Q: While the superficial dermal component of a Genital naevus may display mild cytological atypia, benignity is supported by the presence of cellular [...] with increasing depth into the stroma.
Genital naevus. Deeply pigmented cells extending deeply into the underlying stroma with evidence of cellular maturation.
Genital naevus. High-power view of maturation of cells in the stroma.
A: maturation
Back Extra: Genital naevus
- Clinical: Genital naevi are uniformly pigmented, well-circumscribed, solitary macules or papules, up to 10 mm in size, that typically arise in young adults.
- Micro: The junctional component consists of single cells and nests haphazardly distributed along the epidermal rete ridges, often oriented parallel to the epidermal surface, with focal retraction artefact and dyscohesion.
- Ancillary: Most genital naevi have BRAF p.V600E mutations.
Reference Gallery:
Genital naevus. Deeply pigmented cells extending deeply into the underlying stroma with evidence of cellular maturation.
Genital naevus. High-power view of maturation of cells in the stroma.
Genital naevus. A pigmented plaque-like lesion of the vulva.
Genital naevus. Genital naevus on the glans. Black macule on a 34-year-old man.
Genital naevus. There is a junctional component of single cells and small nests. The cells of the dermal component display mild atypia.
Vulvar naevus. The lesion has a junctional component of nests, with focal retraction artefact and dyscohesion, distributed haphazardly along the epidermal rete ridges; some are oriented parallel to the epidermal surface. The dermal component displays mild cytological atypia superficially but shows maturation with increasing depth.
Vulvar naevus. The lesion has a junctional component of nests, with focal retraction artefact and dyscohesion, distributed haphazardly along the epidermal rete ridges; some are oriented parallel to the epidermal surface. The dermal component displays mild cytological atypia superficially but shows maturation with increasing depth.

Q: Clinically, a Halo Naevus classically presents as a central papular pigmented lesion surrounded by a symmetrical [...].
Halo naevus. A papular pigmented lesion surrounded by a symmetrical depigmented halo, in a background of tan skin.
Halo naevus. Dermoscopic features. White halo with increased vascularization of the underlying dermal plexus. Small papule with residual structureless brown pigmentation. The lesion was excised because it was the only halo naevus in an adult patient, and histopathology confirmed a halo naevus.
A: depigmented halo
Back Extra: Halo Naevus
- Clinical: Halo naevi often arise during the summer, are most common in teenagers and young adults, and are associated with dysplastic naevi. They can present as a papular pigmented lesion surrounded by a depigmented halo.
- Micro: Halo naevi show a dense lymphocytic infiltrate that partially or completely obscures the naevus cells. Melanin-laden histiocytes and mast cells may be present. Hyperchromatism and mild to moderate pleomorphism are reactive changes.
- Ancillary: Immunohistochemistry with SOX10 or melan-A can help delineate the naevus cells, while PRAME is usually negative.
Reference Gallery:
Halo naevus. A papular pigmented lesion surrounded by a symmetrical depigmented halo, in a background of tan skin.
Halo naevus. A well-circumscribed lesion that at first glance could be mistaken for a lymphocytic infiltrate. Infiltrating lymphocytes are intimately admixed with naevus cells, which will lead to apoptosis and ultimately the disappearance of the naevus cells. In later examples, the naevus cells are less conspicuous than in this field.
Halo naevus. Dermoscopic features. White halo with increased vascularization of the underlying dermal plexus. Small papule with residual structureless brown pigmentation. The lesion was excised because it was the only halo naevus in an adult patient, and histopathology confirmed a halo naevus.

Q: Histologically, the characteristic finding in a Halo Naevus is a dense [...] that intimately admixes with and often obscures the underlying nevus cells.
Halo naevus. A well-circumscribed lesion that at first glance could be mistaken for a lymphocytic infiltrate. Infiltrating lymphocytes are intimately admixed with naevus cells, which will lead to apoptosis and ultimately the disappearance of the naevus cells. In later examples, the naevus cells are less conspicuous than in this field.
A: lymphocytic infiltrate
Back Extra: Halo Naevus
- Clinical: Halo naevi often arise during the summer, are most common in teenagers and young adults, and are associated with dysplastic naevi. They can present as a papular pigmented lesion surrounded by a depigmented halo.
- Micro: Halo naevi show a dense lymphocytic infiltrate that partially or completely obscures the naevus cells. Melanin-laden histiocytes and mast cells may be present. Hyperchromatism and mild to moderate pleomorphism are reactive changes.
- Ancillary: Immunohistochemistry with SOX10 or melan-A can help delineate the naevus cells, while PRAME is usually negative.
Reference Gallery:
Halo naevus. A papular pigmented lesion surrounded by a symmetrical depigmented halo, in a background of tan skin.
Halo naevus. A well-circumscribed lesion that at first glance could be mistaken for a lymphocytic infiltrate. Infiltrating lymphocytes are intimately admixed with naevus cells, which will lead to apoptosis and ultimately the disappearance of the naevus cells. In later examples, the naevus cells are less conspicuous than in this field.
Halo naevus. Dermoscopic features. White halo with increased vascularization of the underlying dermal plexus. Small papule with residual structureless brown pigmentation. The lesion was excised because it was the only halo naevus in an adult patient, and histopathology confirmed a halo naevus.

Q: Microscopically, Simple lentigo and lentiginous melanocytic naevus exist on a morphologic spectrum; simple lentigo features elongated rete ridges and increased [...] in the basal epidermis, whereas the nevus stage is defined by true nest formation.
Simple lentigo. Slightly elongated rete with epidermal pigmentation and individual pattern of melanocytes in the basal epidermis.
A: individual melanocytes
Back Extra: Simple lentigo and lentiginous melanocytic naevus
- Clinical: Simple lentigo and lentiginous melanocytic naevus are benign, pigmented lesions that are typically < 6 mm in diameter, symmetrical, and uniformly pigmented.
- Micro: Simple lentigo is characterized by hyperpigmentation of the basal layer epidermal keratinocytes with elongated rete ridges and increased individual melanocytes. Lentiginous naevi have nests of melanocytes.
- Ancillary: Simple lentigines lack BRAF p.V600E mutations.
Reference Gallery:
Simple lentigo. Slightly elongated rete with epidermal pigmentation and individual pattern of melanocytes in the basal epidermis.
Lentiginous junctional naevus. A small, symmetrical, macular or slightly raised, uniformly pigmented lesion.

Q: Clinically, Simple lentigo and lentiginous melanocytic naevus typically present as benign, symmetrical, and uniformly pigmented macules or slightly raised lesions that are [...] in maximum diameter.
Lentiginous junctional naevus. A small, symmetrical, macular or slightly raised, uniformly pigmented lesion.
A: < 6 mm
Back Extra: Simple lentigo and lentiginous melanocytic naevus
- Clinical: Simple lentigo and lentiginous melanocytic naevus are benign, pigmented lesions that are typically < 6 mm in diameter, symmetrical, and uniformly pigmented.
- Micro: Simple lentigo is characterized by hyperpigmentation of the basal layer epidermal keratinocytes with elongated rete ridges and increased individual melanocytes. Lentiginous naevi have nests of melanocytes.
- Ancillary: Simple lentigines lack BRAF p.V600E mutations.
Reference Gallery:
Simple lentigo. Slightly elongated rete with epidermal pigmentation and individual pattern of melanocytes in the basal epidermis.
Lentiginous junctional naevus. A small, symmetrical, macular or slightly raised, uniformly pigmented lesion.

Q: In Circumscribed Meningeal Melanocytic Neoplasms, the microscopic appearance varies; benign melanocytomas exhibit densely packed, slightly spindled or oval tumor cells, whereas malignant melanomas demonstrate increased cellularity, mitoses, and prominent [...].
Meningeal melanocytoma. A melanocytoma, harbouring a GNAQ p.Q209L mutation, is composed of densely packed, slightly spindled or oval tumour cells containing variable melanin pigment.
Meningeal melanoma. The tumour is composed of pleomorphic cells arranged in loose nests.
A: pleomorphism
Q: Circumscribed Meningeal Melanocytic Neoplasms
- Clinical: Patients with [...] typically present with focal neurological signs related to compression of the CNS, such as headaches, seizures, or motor deficits.
- Micro: Meningeal melanocytomas are characterized by densely packed, slightly spindled or oval tumour cells with variable melanin pigment, while meningeal melanomas are more cellular and pleomorphic with increased mitoses.
- Ancillary: Immunohistochemistry shows strong expression of S100, melan-A, HMB45, and MITF in [...]. Absence of nuclear BAP1 staining indicates BAP1 inactivation.
Reference Gallery:
Meningeal melanocytoma. A melanocytoma, harbouring a GNAQ p.Q209L mutation, is composed of densely packed, slightly spindled or oval tumour cells containing variable melanin pigment.
Meningeal melanoma. The tumour is composed of pleomorphic cells arranged in loose nests.
Meningeal melanoma. The tumour shows loss of nuclear BAP1 expression immunohistochemically, corresponding at the molecular level to a BAP1 p.Q267 frameshift mutation in this case.
Meningeal melanocytoma. The lesion shows strong contrast enhancement (T1-weighted MRI).
Meningeal melanocytoma. The tumour does not show marked nuclear polymorphism.
Meningeal melanoma. This GNA11-mutant meningeal melanoma shows a prominent epithelioid cytology and variable melanin content.
Meningeal melanoma. A nested architecture and epithelioid cytology characterize this spinal tumour.
Meningeal melanocytoma, intermediate grade. This tumour, affecting the tentorium, is composed of rounded cells without marked nuclear polymorphism but with increased mitotic activity. The tumour carries GNA11 and EIF1AX mutations.
Meningeal melanocytoma, intermediate grade. This GNAQ-mutant tumour diffusely infiltrates CNS tissue of the filum terminale. The surrounding nervous tissue shows marked gliosis and Rosenthal fibres.
A: Circumscribed Meningeal Melanocytic Neoplasms; Circumscribed Meningeal Melanocytic Neoplasms

Q: In Circumscribed Meningeal Melanocytic Neoplasms, aggressive variants such as meningeal melanomas may harbor specific mutations that result in the immunohistochemical loss of nuclear [...] expression.
Meningeal melanoma. The tumour shows loss of nuclear BAP1 expression immunohistochemically, corresponding at the molecular level to a BAP1 p.Q267 frameshift mutation in this case.
A: BAP1
Q: Circumscribed Meningeal Melanocytic Neoplasms
- Clinical: Patients with [...] typically present with focal neurological signs related to compression of the CNS, such as headaches, seizures, or motor deficits.
- Micro: Meningeal melanocytomas are characterized by densely packed, slightly spindled or oval tumour cells with variable melanin pigment, while meningeal melanomas are more cellular and pleomorphic with increased mitoses.
- Ancillary: Immunohistochemistry shows strong expression of S100, melan-A, HMB45, and MITF in [...]. Absence of nuclear BAP1 staining indicates BAP1 inactivation.
Reference Gallery:
Meningeal melanocytoma. A melanocytoma, harbouring a GNAQ p.Q209L mutation, is composed of densely packed, slightly spindled or oval tumour cells containing variable melanin pigment.
Meningeal melanoma. The tumour is composed of pleomorphic cells arranged in loose nests.
Meningeal melanoma. The tumour shows loss of nuclear BAP1 expression immunohistochemically, corresponding at the molecular level to a BAP1 p.Q267 frameshift mutation in this case.
Meningeal melanocytoma. The lesion shows strong contrast enhancement (T1-weighted MRI).
Meningeal melanocytoma. The tumour does not show marked nuclear polymorphism.
Meningeal melanoma. This GNA11-mutant meningeal melanoma shows a prominent epithelioid cytology and variable melanin content.
Meningeal melanoma. A nested architecture and epithelioid cytology characterize this spinal tumour.
Meningeal melanocytoma, intermediate grade. This tumour, affecting the tentorium, is composed of rounded cells without marked nuclear polymorphism but with increased mitotic activity. The tumour carries GNA11 and EIF1AX mutations.
Meningeal melanocytoma, intermediate grade. This GNAQ-mutant tumour diffusely infiltrates CNS tissue of the filum terminale. The surrounding nervous tissue shows marked gliosis and Rosenthal fibres.
A: Circumscribed Meningeal Melanocytic Neoplasms; Circumscribed Meningeal Melanocytic Neoplasms

Q: Patients presenting with focal neurological signs from CNS compression and demonstrating strong contrast-enhancing meningeal lesions on T1-weighted MRI may be diagnosed with [...].
Meningeal melanocytoma. The lesion shows strong contrast enhancement (T1-weighted MRI).
A: Circumscribed Meningeal Melanocytic Neoplasms
Q: Circumscribed Meningeal Melanocytic Neoplasms
- Clinical: Patients with [...] typically present with focal neurological signs related to compression of the CNS, such as headaches, seizures, or motor deficits.
- Micro: Meningeal melanocytomas are characterized by densely packed, slightly spindled or oval tumour cells with variable melanin pigment, while meningeal melanomas are more cellular and pleomorphic with increased mitoses.
- Ancillary: Immunohistochemistry shows strong expression of S100, melan-A, HMB45, and MITF in [...]. Absence of nuclear BAP1 staining indicates BAP1 inactivation.
Reference Gallery:
Meningeal melanocytoma. A melanocytoma, harbouring a GNAQ p.Q209L mutation, is composed of densely packed, slightly spindled or oval tumour cells containing variable melanin pigment.
Meningeal melanoma. The tumour is composed of pleomorphic cells arranged in loose nests.
Meningeal melanoma. The tumour shows loss of nuclear BAP1 expression immunohistochemically, corresponding at the molecular level to a BAP1 p.Q267 frameshift mutation in this case.
Meningeal melanocytoma. The lesion shows strong contrast enhancement (T1-weighted MRI).
Meningeal melanocytoma. The tumour does not show marked nuclear polymorphism.
Meningeal melanoma. This GNA11-mutant meningeal melanoma shows a prominent epithelioid cytology and variable melanin content.
Meningeal melanoma. A nested architecture and epithelioid cytology characterize this spinal tumour.
Meningeal melanocytoma, intermediate grade. This tumour, affecting the tentorium, is composed of rounded cells without marked nuclear polymorphism but with increased mitotic activity. The tumour carries GNA11 and EIF1AX mutations.
Meningeal melanocytoma, intermediate grade. This GNAQ-mutant tumour diffusely infiltrates CNS tissue of the filum terminale. The surrounding nervous tissue shows marked gliosis and Rosenthal fibres.
A: Circumscribed Meningeal Melanocytic Neoplasms; Circumscribed Meningeal Melanocytic Neoplasms

Q: Microscopic evaluation of [...] reveals benign pigmented cells restricted to the leptomeninges in the benign form (melanocytosis), whereas the malignant form (melanomatosis) demonstrates cytologic atypia, mitotic activity, and diffuse invasion into the underlying brain parenchyma.
Meningeal melanocytosis. Melanocytic cells with benign features diffusely proliferate within the meninges between the nerve roots of the lower spinal cord.
Meningeal melanomatosis. Malignant melanocytic cells diffusely infiltrate the underlying brain parenchyma. The tumour carries an NRAS p.Q61R mutation.
A: Diffuse Meningeal Melanocytic Neoplasms: Melanocytosis and Melanomatosis
Back Extra: Diffuse Meningeal Melanocytic Neoplasms: Melanocytosis and Melanomatosis
- Clinical: Neurological symptoms can arise from either hydrocephalus or local effects on the CNS parenchyma; symptoms progress rapidly once malignant transformation occurs.
- Micro: Meningeal melanocytosis shows benign melanocytic cells in the meninges, while melanomatosis demonstrates invasive and atypical cells with mitotic activity and necrosis.
- Ancillary: Somatic mutations in NRAS are common, and BRAF mutations occur in a minority of cases. Diagnostic molecular pathology is crucial for distinguishing primary from metastatic disease.
Reference Gallery:
Meningeal melanomatosis. Macroscopy of meningeal melanomatosis in a child with neurocutaneous melanosis who succumbed at the age of 17 months due to rapid disease progression.
Meningeal melanocytosis. Melanocytic cells with benign features diffusely proliferate within the meninges between the nerve roots of the lower spinal cord.
Meningeal melanomatosis. T1-weighted axial MRI revealing a hyperintense, contrast-enhancing lesion outlining the gyri and sulci in the left frontal-parietal-occipital region in a 5-year-old child.
Meningeal melanomatosis. Macroscopic appearance of the cerebral tissue shows brownish discolouration of the thickened leptomeninges and black discolouration of the underlying cerebral cortex.
Meningeal melanomatosis. Malignant melanocytic cells diffusely infiltrate the underlying brain parenchyma. The tumour carries an NRAS p.Q61R mutation.
Meningeal melanomatosis. A subpopulation of melanoma cells are heavily pigmented.
Melanoma arising from meningeal melanocytosis. Meningeal melanoma in an adult with neurocutaneous melanosis and melanocytosis. The melanoma cells infiltrate the surrounding brain tissue.
Melanoma arising from meningeal melanocytosis. The meningeal melanoma infiltrates the brain, spreading along the small vessels (angiotropism).

Q: Gross examination of [...] characteristically reveals striking brownish to black discoloration of the thickened leptomeninges and underlying cerebral cortex due to extensive melanin deposition.
Meningeal melanomatosis. Macroscopic appearance of the cerebral tissue shows brownish discolouration of the thickened leptomeninges and black discolouration of the underlying cerebral cortex.
A: Diffuse Meningeal Melanocytic Neoplasms: Melanocytosis and Melanomatosis
Back Extra: Diffuse Meningeal Melanocytic Neoplasms: Melanocytosis and Melanomatosis
- Clinical: Neurological symptoms can arise from either hydrocephalus or local effects on the CNS parenchyma; symptoms progress rapidly once malignant transformation occurs.
- Micro: Meningeal melanocytosis shows benign melanocytic cells in the meninges, while melanomatosis demonstrates invasive and atypical cells with mitotic activity and necrosis.
- Ancillary: Somatic mutations in NRAS are common, and BRAF mutations occur in a minority of cases. Diagnostic molecular pathology is crucial for distinguishing primary from metastatic disease.
Reference Gallery:
Meningeal melanomatosis. Macroscopy of meningeal melanomatosis in a child with neurocutaneous melanosis who succumbed at the age of 17 months due to rapid disease progression.
Meningeal melanocytosis. Melanocytic cells with benign features diffusely proliferate within the meninges between the nerve roots of the lower spinal cord.
Meningeal melanomatosis. T1-weighted axial MRI revealing a hyperintense, contrast-enhancing lesion outlining the gyri and sulci in the left frontal-parietal-occipital region in a 5-year-old child.
Meningeal melanomatosis. Macroscopic appearance of the cerebral tissue shows brownish discolouration of the thickened leptomeninges and black discolouration of the underlying cerebral cortex.
Meningeal melanomatosis. Malignant melanocytic cells diffusely infiltrate the underlying brain parenchyma. The tumour carries an NRAS p.Q61R mutation.
Meningeal melanomatosis. A subpopulation of melanoma cells are heavily pigmented.
Melanoma arising from meningeal melanocytosis. Meningeal melanoma in an adult with neurocutaneous melanosis and melanocytosis. The melanoma cells infiltrate the surrounding brain tissue.
Melanoma arising from meningeal melanocytosis. The meningeal melanoma infiltrates the brain, spreading along the small vessels (angiotropism).

Q: Neuroimaging (T1-weighted MRI) of [...] typically reveals diffuse, hyperintense, contrast-enhancing lesions that distinctly outline the affected cerebral gyri and sulci.
Meningeal melanomatosis. T1-weighted axial MRI revealing a hyperintense, contrast-enhancing lesion outlining the gyri and sulci in the left frontal-parietal-occipital region in a 5-year-old child.
A: Diffuse Meningeal Melanocytic Neoplasms: Melanocytosis and Melanomatosis
Back Extra: Diffuse Meningeal Melanocytic Neoplasms: Melanocytosis and Melanomatosis
- Clinical: Neurological symptoms can arise from either hydrocephalus or local effects on the CNS parenchyma; symptoms progress rapidly once malignant transformation occurs.
- Micro: Meningeal melanocytosis shows benign melanocytic cells in the meninges, while melanomatosis demonstrates invasive and atypical cells with mitotic activity and necrosis.
- Ancillary: Somatic mutations in NRAS are common, and BRAF mutations occur in a minority of cases. Diagnostic molecular pathology is crucial for distinguishing primary from metastatic disease.
Reference Gallery:
Meningeal melanomatosis. Macroscopy of meningeal melanomatosis in a child with neurocutaneous melanosis who succumbed at the age of 17 months due to rapid disease progression.
Meningeal melanocytosis. Melanocytic cells with benign features diffusely proliferate within the meninges between the nerve roots of the lower spinal cord.
Meningeal melanomatosis. T1-weighted axial MRI revealing a hyperintense, contrast-enhancing lesion outlining the gyri and sulci in the left frontal-parietal-occipital region in a 5-year-old child.
Meningeal melanomatosis. Macroscopic appearance of the cerebral tissue shows brownish discolouration of the thickened leptomeninges and black discolouration of the underlying cerebral cortex.
Meningeal melanomatosis. Malignant melanocytic cells diffusely infiltrate the underlying brain parenchyma. The tumour carries an NRAS p.Q61R mutation.
Meningeal melanomatosis. A subpopulation of melanoma cells are heavily pigmented.
Melanoma arising from meningeal melanocytosis. Meningeal melanoma in an adult with neurocutaneous melanosis and melanocytosis. The melanoma cells infiltrate the surrounding brain tissue.
Melanoma arising from meningeal melanocytosis. The meningeal melanoma infiltrates the brain, spreading along the small vessels (angiotropism).

Q: Clinically, a Meyerson Nevus classically presents as a central nevus surrounded by a symmetrical erythematous and [...] halo.
Meyerson nevus. A central nevus is surrounded by a symmetrical erythematous eczematous plaque.
A: eczematous
Back Extra: Meyerson Nevus
- Clinical: Meyerson nevus typically presents as a central nevus surrounded by a symmetrical erythematous and eczematous halo, often found on the trunk and proximal extremities.
- Micro: Histologically, a Meyerson nevus shows a compound nevus with associated epidermal acanthosis, spongiosis, and parakeratosis.
- Ancillary: Differential diagnosis includes halo nevi and melanomas, but Meyerson nevi can be distinguished by the presence of a spongiotic dermatitis and a predominance of CD4-positive T cells.
Reference Gallery:
Meyerson nevus. A compound nevus is associated with epidermal acanthosis, spongiosis, and parakeratosis.
Meyerson nevus. A central nevus is surrounded by a symmetrical erythematous eczematous plaque.

Q: Histologically, a Meyerson Nevus typically features a compound nevus with associated epidermal acanthosis, parakeratosis, and [...].
Meyerson nevus. A compound nevus is associated with epidermal acanthosis, spongiosis, and parakeratosis.
A: spongiosis
Back Extra: Meyerson Nevus
- Clinical: Meyerson nevus typically presents as a central nevus surrounded by a symmetrical erythematous and eczematous halo, often found on the trunk and proximal extremities.
- Micro: Histologically, a Meyerson nevus shows a compound nevus with associated epidermal acanthosis, spongiosis, and parakeratosis.
- Ancillary: Differential diagnosis includes halo nevi and melanomas, but Meyerson nevi can be distinguished by the presence of a spongiotic dermatitis and a predominance of CD4-positive T cells.
Reference Gallery:
Meyerson nevus. A compound nevus is associated with epidermal acanthosis, spongiosis, and parakeratosis.
Meyerson nevus. A central nevus is surrounded by a symmetrical erythematous eczematous plaque.

Q: Microscopically, MITF pathway-activated melanocytic tumors are characterized by large cells with copious [...] or granular cytoplasm, often arranged in dense sheets and fascicles that infiltrate the dermis.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. The proliferation infiltrates the dermis and subcutis, and it is organized in dense sheets and fascicles. Arborescent small blood vessels are closely intermingled with the tumour. Small nerve structures are visible within the tumour without clear-cut neurotropism.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Cytological features show little variation from top to bottom. The cells are large cells with a copious foamy or optically clear cytoplasm and an oval or spindle-shaped nucleus. There is mild nuclear pleomorphism and sparse mitotic activity (1 mitosis/mm2).
A: optically clear
Back Extra: MITF pathway-activated melanocytic tumours
- Clinical: These tumours typically present as solitary unpigmented nodules on the distal extremities and trunk, with a female predilection for ACT::MITF translocation cases.
- Micro: The tumour cells are large with copious optically clear or granular cytoplasm, forming dense sheets and fascicles, and infiltrating the dermis and subcutis.
- Ancillary: Immunohistochemical staining shows positivity for HMB45, melan-A (MART1), S100, and MITF. Molecular testing confirms ACT::MITF or MITF::CREM translocations.
Reference Gallery:
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Tumour cells show a cytoplasmic expression of HMB45.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. The proliferation infiltrates the dermis and subcutis, and it is organized in dense sheets and fascicles. Arborescent small blood vessels are closely intermingled with the tumour. Small nerve structures are visible within the tumour without clear-cut neurotropism.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Cytological features show little variation from top to bottom. The cells are large cells with a copious foamy or optically clear cytoplasm and an oval or spindle-shaped nucleus. There is mild nuclear pleomorphism and sparse mitotic activity (1 mitosis/mm2).
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Tumour cells show a nuclear expression of MITF.
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Poorly defined intradermal nodule displaying a central sheet-like and fascicular pattern and extending both towards the epidermis and towards the subcutis, as small nests or isolated cells.
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Tumour cells are arranged in fascicles, intermingled with collagen bundles.
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Cytological atypia is moderate to severe. There are areas in which tumour cells exhibit extensive granular cytoplasm and small oval or spindled nuclei, alternating with areas in which tumour cells contain hyperchromatic nuclei surrounded by limited cytoplasm.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Massive infiltration of the dermis and subcutis by a cellular, ill-limited tumoural nodule.

Q: Immunohistochemical evaluation of MITF pathway-activated melanocytic tumors characteristically reveals cytoplasmic positivity for HMB45 alongside diagnostic nuclear expression of [...].
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Tumour cells show a cytoplasmic expression of HMB45.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Tumour cells show a nuclear expression of MITF.
A: MITF
Back Extra: MITF pathway-activated melanocytic tumours
- Clinical: These tumours typically present as solitary unpigmented nodules on the distal extremities and trunk, with a female predilection for ACT::MITF translocation cases.
- Micro: The tumour cells are large with copious optically clear or granular cytoplasm, forming dense sheets and fascicles, and infiltrating the dermis and subcutis.
- Ancillary: Immunohistochemical staining shows positivity for HMB45, melan-A (MART1), S100, and MITF. Molecular testing confirms ACT::MITF or MITF::CREM translocations.
Reference Gallery:
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Tumour cells show a cytoplasmic expression of HMB45.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. The proliferation infiltrates the dermis and subcutis, and it is organized in dense sheets and fascicles. Arborescent small blood vessels are closely intermingled with the tumour. Small nerve structures are visible within the tumour without clear-cut neurotropism.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Cytological features show little variation from top to bottom. The cells are large cells with a copious foamy or optically clear cytoplasm and an oval or spindle-shaped nucleus. There is mild nuclear pleomorphism and sparse mitotic activity (1 mitosis/mm2).
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Tumour cells show a nuclear expression of MITF.
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Poorly defined intradermal nodule displaying a central sheet-like and fascicular pattern and extending both towards the epidermis and towards the subcutis, as small nests or isolated cells.
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Tumour cells are arranged in fascicles, intermingled with collagen bundles.
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Cytological atypia is moderate to severe. There are areas in which tumour cells exhibit extensive granular cytoplasm and small oval or spindled nuclei, alternating with areas in which tumour cells contain hyperchromatic nuclei surrounded by limited cytoplasm.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Massive infiltration of the dermis and subcutis by a cellular, ill-limited tumoural nodule.

Q: Molecular testing of MITF pathway-activated melanocytic tumors confirms the diagnosis by identifying characteristic gene fusions, most notably the [MITF or MITF::CREM] translocations.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Cytological features show little variation from top to bottom. The cells are large cells with a copious foamy or optically clear cytoplasm and an oval or spindle-shaped nucleus. There is mild nuclear pleomorphism and sparse mitotic activity (1 mitosis/mm2).
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Poorly defined intradermal nodule displaying a central sheet-like and fascicular pattern and extending both towards the epidermis and towards the subcutis, as small nests or isolated cells.
A: ACT
Back Extra: MITF pathway-activated melanocytic tumours
- Clinical: These tumours typically present as solitary unpigmented nodules on the distal extremities and trunk, with a female predilection for ACT::MITF translocation cases.
- Micro: The tumour cells are large with copious optically clear or granular cytoplasm, forming dense sheets and fascicles, and infiltrating the dermis and subcutis.
- Ancillary: Immunohistochemical staining shows positivity for HMB45, melan-A (MART1), S100, and MITF. Molecular testing confirms ACT::MITF or MITF::CREM translocations.
Reference Gallery:
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Tumour cells show a cytoplasmic expression of HMB45.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. The proliferation infiltrates the dermis and subcutis, and it is organized in dense sheets and fascicles. Arborescent small blood vessels are closely intermingled with the tumour. Small nerve structures are visible within the tumour without clear-cut neurotropism.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Cytological features show little variation from top to bottom. The cells are large cells with a copious foamy or optically clear cytoplasm and an oval or spindle-shaped nucleus. There is mild nuclear pleomorphism and sparse mitotic activity (1 mitosis/mm2).
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Tumour cells show a nuclear expression of MITF.
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Poorly defined intradermal nodule displaying a central sheet-like and fascicular pattern and extending both towards the epidermis and towards the subcutis, as small nests or isolated cells.
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Tumour cells are arranged in fascicles, intermingled with collagen bundles.
Clear cell tumour with melanocytic differentiation and MITF::CREM translocation. Cytological atypia is moderate to severe. There are areas in which tumour cells exhibit extensive granular cytoplasm and small oval or spindled nuclei, alternating with areas in which tumour cells contain hyperchromatic nuclei surrounded by limited cytoplasm.
Clear cell tumour with melanocytic differentiation and ACT::MITF translocation. Massive infiltration of the dermis and subcutis by a cellular, ill-limited tumoural nodule.

Q: Histologically, Melanosis is characterized by melanin deposition in basilar keratinocytes with a roughly [...] number of melanocytes at the dermoepidermal junction.
Vulvar melanosis. There are elongate rete ridges. Pigmentation is restricted to the keratinocytes of the basal layer, with a roughly normal number of melanocytes at the junction.
Vulvar melanosis. Melanocytes are inconspicuous, and rare melanophages are present in the superficial dermis.
A: normal
Back Extra: Melanosis
- Clinical: Melanosis presents as single or multiple asymptomatic pigmented macules or patches with inhomogeneous black or brown coloration and poorly defined borders.
- Micro: Characterized by melanin pigment deposited in basilar keratinocytes, occasionally with elongated rete ridges and melanophages in the papillary dermis.
- Ancillary: Immunohistochemistry shows positive staining for melanocytic markers such as melan-A, MITF, HMB45, and SOX10.
Reference Gallery:
Vulvar melanosis. 52-year-old woman. Multifocal pigmented lesion with non-homogeneous pigmentation.
Vulvar melanosis. Dermoscopically, irregular diffuse pigmentation characterized by the presence of shades of brown and black colouring in the absence of other dermoscopic parameters.
Vulvar melanosis. There are elongate rete ridges. Pigmentation is restricted to the keratinocytes of the basal layer, with a roughly normal number of melanocytes at the junction.
Vulvar melanosis. Melanocytes are inconspicuous, and rare melanophages are present in the superficial dermis.
Penile melanosis. Multifocal pigmented lesion with non-homogeneous pigmentation.
Benign epithelial melanosis of the conjunctiva. Conjunctival epithelium is pigmented, with some melanophages present in the substantia propria as well. Melanocytes, however, appear normal.
Benign epithelial melanosis of the conjunctiva. A melan-A (MART1) immunostain confirms normal density of dendritic-appearing melanocytes.

Q: Clinically, [...] presents as single or multiple asymptomatic pigmented macules or patches with inhomogeneous black or brown coloration and poorly defined borders on mucosal or cutaneous surfaces.
Vulvar melanosis. 52-year-old woman. Multifocal pigmented lesion with non-homogeneous pigmentation.
Penile melanosis. Multifocal pigmented lesion with non-homogeneous pigmentation.
A: Melanosis
Back Extra: Melanosis
- Clinical: Melanosis presents as single or multiple asymptomatic pigmented macules or patches with inhomogeneous black or brown coloration and poorly defined borders.
- Micro: Characterized by melanin pigment deposited in basilar keratinocytes, occasionally with elongated rete ridges and melanophages in the papillary dermis.
- Ancillary: Immunohistochemistry shows positive staining for melanocytic markers such as melan-A, MITF, HMB45, and SOX10.
Reference Gallery:
Vulvar melanosis. 52-year-old woman. Multifocal pigmented lesion with non-homogeneous pigmentation.
Vulvar melanosis. Dermoscopically, irregular diffuse pigmentation characterized by the presence of shades of brown and black colouring in the absence of other dermoscopic parameters.
Vulvar melanosis. There are elongate rete ridges. Pigmentation is restricted to the keratinocytes of the basal layer, with a roughly normal number of melanocytes at the junction.
Vulvar melanosis. Melanocytes are inconspicuous, and rare melanophages are present in the superficial dermis.
Penile melanosis. Multifocal pigmented lesion with non-homogeneous pigmentation.
Benign epithelial melanosis of the conjunctiva. Conjunctival epithelium is pigmented, with some melanophages present in the substantia propria as well. Melanocytes, however, appear normal.
Benign epithelial melanosis of the conjunctiva. A melan-A (MART1) immunostain confirms normal density of dendritic-appearing melanocytes.

Q: In Melanosis, immunohistochemistry for melanocytic markers like Melan-A (MART1) characteristically highlights a [...] density of dendritic-appearing melanocytes.
Benign epithelial melanosis of the conjunctiva. A melan-A (MART1) immunostain confirms normal density of dendritic-appearing melanocytes.
A: normal
Back Extra: Melanosis
- Clinical: Melanosis presents as single or multiple asymptomatic pigmented macules or patches with inhomogeneous black or brown coloration and poorly defined borders.
- Micro: Characterized by melanin pigment deposited in basilar keratinocytes, occasionally with elongated rete ridges and melanophages in the papillary dermis.
- Ancillary: Immunohistochemistry shows positive staining for melanocytic markers such as melan-A, MITF, HMB45, and SOX10.
Reference Gallery:
Vulvar melanosis. 52-year-old woman. Multifocal pigmented lesion with non-homogeneous pigmentation.
Vulvar melanosis. Dermoscopically, irregular diffuse pigmentation characterized by the presence of shades of brown and black colouring in the absence of other dermoscopic parameters.
Vulvar melanosis. There are elongate rete ridges. Pigmentation is restricted to the keratinocytes of the basal layer, with a roughly normal number of melanocytes at the junction.
Vulvar melanosis. Melanocytes are inconspicuous, and rare melanophages are present in the superficial dermis.
Penile melanosis. Multifocal pigmented lesion with non-homogeneous pigmentation.
Benign epithelial melanosis of the conjunctiva. Conjunctival epithelium is pigmented, with some melanophages present in the substantia propria as well. Melanocytes, however, appear normal.
Benign epithelial melanosis of the conjunctiva. A melan-A (MART1) immunostain confirms normal density of dendritic-appearing melanocytes.

Q: Clinically, Naevus of Ito and Naevus of Ota typically present as congenital or childhood-onset [...], frequently involving the face, sclera, or shoulder regions.
Naevus of Ito. Bluish patch on the right supraclavicular area and shoulder.
Naevus of Ota. Bluish patch on the face, with scleral involvement.
Naevus of Ota. Dark bluish to brown patch on the face in an adult.
A: bluish patches
Back Extra: Naevus of Ito and Naevus of Ota
- Clinical: Naevus of Ito and Naevus of Ota are bluish patches that are present at birth in about 50% of cases or appear before adolescence.
- Micro: Sparse populations of pigmented and dendritic melanocytes are haphazardly dispersed in the upper dermis.
- Ancillary: GNAQ and GNA11 mutations are commonly found in naevi of Ota and Ito.
Reference Gallery:
Naevus of Ito. Bluish patch on the right supraclavicular area and shoulder.
Naevus of Ota. Bluish patch on the face, with scleral involvement.
Naevus of Ota. Dark bluish to brown patch on the face in an adult.
Naevus of Ota. Single dendritic melanocytes are dispersed in the upper dermis.

Q: Microscopically, Naevus of Ito and Naevus of Ota feature a sparse population of pigmented, [...] melanocytes that are haphazardly dispersed within the upper dermis.
Naevus of Ota. Single dendritic melanocytes are dispersed in the upper dermis.
A: dendritic
Back Extra: Naevus of Ito and Naevus of Ota
- Clinical: Naevus of Ito and Naevus of Ota are bluish patches that are present at birth in about 50% of cases or appear before adolescence.
- Micro: Sparse populations of pigmented and dendritic melanocytes are haphazardly dispersed in the upper dermis.
- Ancillary: GNAQ and GNA11 mutations are commonly found in naevi of Ota and Ito.
Reference Gallery:
Naevus of Ito. Bluish patch on the right supraclavicular area and shoulder.
Naevus of Ota. Bluish patch on the face, with scleral involvement.
Naevus of Ota. Dark bluish to brown patch on the face in an adult.
Naevus of Ota. Single dendritic melanocytes are dispersed in the upper dermis.

Q: The clinical presentation of a light-brown patch speckled with darker brown or black macules or papules is characteristic of [...].
Naevus spilus. A large tan patch with multiple small brown macules and papules within it.
Naevus spilus. A smaller form of naevus spilus shows a light-brown patch with three dark-brown macules.
A: Naevus spilus
Back Extra: Naevus spilus
- Clinical: Naevus spilus appears as a light-brown patch with black, brown, or reddish-brown macules or papules within it, typically 30-60 mm in diameter.
- Micro: The background hyperpigmented patch has elongated, hyperpigmented rete ridges with slightly increased numbers of melanocytes. The speckles show variable findings, including those of lentiginous junctional, compound, or intradermal naevi.
- Ancillary: Naevi spilus likely result from a postzygotic HRAS mutation in a melanocyte precursor, with additional alterations in the darker papules.
Reference Gallery:
Naevus spilus. A large tan patch with multiple small brown macules and papules within it.
Naevus spilus. A smaller form of naevus spilus shows a light-brown patch with three dark-brown macules.
Naevus spilus. Scanning magnification reveals subtle elongation of rete. On the right side of the photomicrograph is a compound naevus representing a small papule in the naevus spilus.
Naevus spilus. The tan patch of naevus spilus shows subtle elongate rete with a mildly increased number of small basilar melanocytes.
Naevus spilus. A small dark papule of naevus spilus shows a compound naevus without atypia.

Q: Histologically in Naevus spilus, the background tan patch shows elongated, hyperpigmented rete ridges, while the darker clinical speckles typically represent a localized [...].
Naevus spilus. Scanning magnification reveals subtle elongation of rete. On the right side of the photomicrograph is a compound naevus representing a small papule in the naevus spilus.
Naevus spilus. The tan patch of naevus spilus shows subtle elongate rete with a mildly increased number of small basilar melanocytes.
Naevus spilus. A small dark papule of naevus spilus shows a compound naevus without atypia.
A: junctional, compound, or intradermal nevus
Back Extra: Naevus spilus
- Clinical: Naevus spilus appears as a light-brown patch with black, brown, or reddish-brown macules or papules within it, typically 30-60 mm in diameter.
- Micro: The background hyperpigmented patch has elongated, hyperpigmented rete ridges with slightly increased numbers of melanocytes. The speckles show variable findings, including those of lentiginous junctional, compound, or intradermal naevi.
- Ancillary: Naevi spilus likely result from a postzygotic HRAS mutation in a melanocyte precursor, with additional alterations in the darker papules.
Reference Gallery:
Naevus spilus. A large tan patch with multiple small brown macules and papules within it.
Naevus spilus. A smaller form of naevus spilus shows a light-brown patch with three dark-brown macules.
Naevus spilus. Scanning magnification reveals subtle elongation of rete. On the right side of the photomicrograph is a compound naevus representing a small papule in the naevus spilus.
Naevus spilus. The tan patch of naevus spilus shows subtle elongate rete with a mildly increased number of small basilar melanocytes.
Naevus spilus. A small dark papule of naevus spilus shows a compound naevus without atypia.

Q: Histologically, [...] present as expansile proliferations within the dermal or subcutaneous tissue, often showing sharp demarcation from the surrounding background nevus cells.
Proliferative nodule in congenital melanocytic naevus. A compound giant congenital naevus is observed with multiple proliferative nodules with sharp demarcation from surrounding congenital naevus cells.
Proliferative nodule in congenital melanocytic naevus. Higher magnification of the proliferative nodule shows slightly enlarged epithelioid melanocytes with visible nucleoli and occasional mitotic activity but a lack of high-grade nuclear atypia.
A: Proliferative Nodules in Congenital Melanocytic Nevus
Back Extra: Proliferative Nodules in Congenital Melanocytic Nevus
- Clinical: Proliferative nodules (PNs) in congenital melanocytic nevi are typically < 20 mm in size, can be ulcerated, and may show rapid growth.
- Micro: Within the dermal or subcutaneous portion of a congenital naevus, PNs show an expansile proliferation of melanocytes with various morphologies (spitzoid, small blue round cell, epithelioid, or spindle).
- Ancillary: Gains or losses of entire chromosomes are seen in PNs, whereas melanomas tend to have segmental copy-number aberrations.
Reference Gallery:
Proliferative nodule in congenital melanocytic naevus. A compound giant congenital naevus is observed with multiple proliferative nodules with sharp demarcation from surrounding congenital naevus cells.
Proliferative nodule in congenital melanocytic naevus. Higher magnification of the proliferative nodule shows slightly enlarged epithelioid melanocytes with visible nucleoli and occasional mitotic activity but a lack of high-grade nuclear atypia.
Proliferative nodule in congenital melanocytic naevus. A nodular proliferation consisting of monomorphic small round blue cells filling and expanding the dermis is observed.
Proliferative nodule in congenital melanocytic naevus. Higher magnification shows a monomorphic proliferation of small round blue cells with mitotic activity.

Q: In Proliferative Nodules in Congenital Melanocytic Nevus, the expansile nodules can demonstrate diverse cytomorphologies, including a distinct pattern composed of monomorphic [...] filling and expanding the dermis.
Proliferative nodule in congenital melanocytic naevus. A nodular proliferation consisting of monomorphic small round blue cells filling and expanding the dermis is observed.
Proliferative nodule in congenital melanocytic naevus. Higher magnification shows a monomorphic proliferation of small round blue cells with mitotic activity.
A: small round blue cells
Back Extra: Proliferative Nodules in Congenital Melanocytic Nevus
- Clinical: Proliferative nodules (PNs) in congenital melanocytic nevi are typically < 20 mm in size, can be ulcerated, and may show rapid growth.
- Micro: Within the dermal or subcutaneous portion of a congenital naevus, PNs show an expansile proliferation of melanocytes with various morphologies (spitzoid, small blue round cell, epithelioid, or spindle).
- Ancillary: Gains or losses of entire chromosomes are seen in PNs, whereas melanomas tend to have segmental copy-number aberrations.
Reference Gallery:
Proliferative nodule in congenital melanocytic naevus. A compound giant congenital naevus is observed with multiple proliferative nodules with sharp demarcation from surrounding congenital naevus cells.
Proliferative nodule in congenital melanocytic naevus. Higher magnification of the proliferative nodule shows slightly enlarged epithelioid melanocytes with visible nucleoli and occasional mitotic activity but a lack of high-grade nuclear atypia.
Proliferative nodule in congenital melanocytic naevus. A nodular proliferation consisting of monomorphic small round blue cells filling and expanding the dermis is observed.
Proliferative nodule in congenital melanocytic naevus. Higher magnification shows a monomorphic proliferation of small round blue cells with mitotic activity.

Q: Clinically and dermoscopically, a Recurrent Naevus presents as irregular pigmentation that is characteristically confined to the boundaries of a prior surgical [...].
Recurrent naevus. Irregular pigmentation involves a dermal scar related to previous naevus removal. Importantly, this pigmentation does not extend beyond the confines of the scar.
Recurrent naevus. Dermoscopy reveals radial lines, irregular clods, and centrifugal growth patterns confined to the scar.
A: scar
Back Extra: Recurrent Naevus
- Clinical: Recurrent naevus manifests as an area of pigmentation within a scar, often causing clinical concern for melanoma.
- Micro: Histopathology shows an atypical junctional and superficial dermal melanocytic proliferation overlying a scar, with mild to moderate cytological atypia.
- Ancillary: The proliferation rate in recurrent naevi is low, and immunohistochemistry for tyrosinase or HMB45 antigen shows decreased immunoreactivity in deeper cells.
Reference Gallery:
Recurrent naevus. Trizonal pattern of recurrent naevus with atypical junctional component and dermal scar overlying residual banal dermal naevus.
Recurrent naevus. The junctional component is predominantly lentiginous and composed of epithelioid melanocytes overlying dermal scar.
Recurrent naevus. Irregular pigmentation involves a dermal scar related to previous naevus removal. Importantly, this pigmentation does not extend beyond the confines of the scar.
Recurrent naevus. Dermoscopy reveals radial lines, irregular clods, and centrifugal growth patterns confined to the scar.

Q: Histopathologically, a Recurrent Naevus characteristically exhibits a [...] pattern, consisting of an atypical junctional melanocytic proliferation, an underlying dermal scar, and residual banal dermal melanocytes at the base.
Recurrent naevus. Trizonal pattern of recurrent naevus with atypical junctional component and dermal scar overlying residual banal dermal naevus.
Recurrent naevus. The junctional component is predominantly lentiginous and composed of epithelioid melanocytes overlying dermal scar.
A: trizonal
Back Extra: Recurrent Naevus
- Clinical: Recurrent naevus manifests as an area of pigmentation within a scar, often causing clinical concern for melanoma.
- Micro: Histopathology shows an atypical junctional and superficial dermal melanocytic proliferation overlying a scar, with mild to moderate cytological atypia.
- Ancillary: The proliferation rate in recurrent naevi is low, and immunohistochemistry for tyrosinase or HMB45 antigen shows decreased immunoreactivity in deeper cells.
Reference Gallery:
Recurrent naevus. Trizonal pattern of recurrent naevus with atypical junctional component and dermal scar overlying residual banal dermal naevus.
Recurrent naevus. The junctional component is predominantly lentiginous and composed of epithelioid melanocytes overlying dermal scar.
Recurrent naevus. Irregular pigmentation involves a dermal scar related to previous naevus removal. Importantly, this pigmentation does not extend beyond the confines of the scar.
Recurrent naevus. Dermoscopy reveals radial lines, irregular clods, and centrifugal growth patterns confined to the scar.

Q: Histologically, Solar Lentigo presents as a well-demarcated intraepidermal proliferation of bland keratinocytes featuring [...] with occasional fusion.
Solar lentigo. Elongated rete ridges with occasional fusion are characteristic of the solar lentigo.
A: elongated rete ridges
Back Extra: Solar Lentigo
- Clinical: Solar lentigines present as small, uniformly pigmented tan to brown macules, most commonly found on chronically sun-exposed skin, particularly of the face, forearms, and dorsal aspects of the hands.
- Micro: Solar lentigines are well-demarcated intraepidermal proliferations of bland basaloid keratinocytes with elongated rete ridges and hyperpigmentation of the basal cell layer.
- Ancillary: Solar lentigines may show mutations in the FGFR3 and PIK3CA genes, but typically lack BRAF mutations.
Reference Gallery:
Solar lentigo. Elongated rete ridges with occasional fusion are characteristic of the solar lentigo.
Solar lentigo. Basal cell layer hyperpigmentation accentuated at the tips of the rete ridges is frequently seen in solar lentigines.

Q: A characteristic microscopic finding in Solar Lentigo is hyperpigmentation of the basal cell layer that is frequently accentuated at the [...].
Solar lentigo. Basal cell layer hyperpigmentation accentuated at the tips of the rete ridges is frequently seen in solar lentigines.
A: tips of the rete ridges
Back Extra: Solar Lentigo
- Clinical: Solar lentigines present as small, uniformly pigmented tan to brown macules, most commonly found on chronically sun-exposed skin, particularly of the face, forearms, and dorsal aspects of the hands.
- Micro: Solar lentigines are well-demarcated intraepidermal proliferations of bland basaloid keratinocytes with elongated rete ridges and hyperpigmentation of the basal cell layer.
- Ancillary: Solar lentigines may show mutations in the FGFR3 and PIK3CA genes, but typically lack BRAF mutations.
Reference Gallery:
Solar lentigo. Elongated rete ridges with occasional fusion are characteristic of the solar lentigo.
Solar lentigo. Basal cell layer hyperpigmentation accentuated at the tips of the rete ridges is frequently seen in solar lentigines.

Q: Histologically, Special-Site Naevi (e.g., from the groin or umbilicus) are characterized by architectural disorder with irregular junctional nests, cytologic atypia, and a classically [...] cellular pattern, but crucially lack increased mitotic activity or necrotic melanocytes.
Special-site naevus of the groin. A nested and discohesive pattern is present with irregular junctional nests.
Special-site naevus of the umbilicus. Irregular nesting arrangement is present with a dyscohesive pattern, junctional cytological atypia, slight pagetoid spread, and dermal fibroplasia.
A: dyscohesive
Back Extra: Special-Site Naevi
- Clinical: Special-site naevi are typically > 6 mm in size, with irregular borders and are often clinically innocuous, though patients may not notice recent changes.
- Micro: These naevi show architectural disorder with asymmetry, irregular junctional nests, cytological atypia, and slight pagetoid spread, but lack increased mitotic activity or necrotic melanocytes.
- Ancillary: Molecular analyses are usually unnecessary for diagnosis; dermoscopy can help differentiate from melanoma based on key features like pigment network and large globules.
Reference Gallery:
Special-site naevi of the breast. Clinical characteristics of breast naevi.
Special-site naevus of the groin. A nested and discohesive pattern is present with irregular junctional nests.
Special-site naevus of the umbilicus. Irregular nesting arrangement is present with a dyscohesive pattern, junctional cytological atypia, slight pagetoid spread, and dermal fibroplasia.

Q: Clinically, pigmented lesions occurring in locations like the breast that are typically > 6 mm with irregular borders—yet remain biologically innocuous without recent changes—are characteristic of [...].
Special-site naevi of the breast. Clinical characteristics of breast naevi.
A: Special-Site Naevi
Back Extra: Special-Site Naevi
- Clinical: Special-site naevi are typically > 6 mm in size, with irregular borders and are often clinically innocuous, though patients may not notice recent changes.
- Micro: These naevi show architectural disorder with asymmetry, irregular junctional nests, cytological atypia, and slight pagetoid spread, but lack increased mitotic activity or necrotic melanocytes.
- Ancillary: Molecular analyses are usually unnecessary for diagnosis; dermoscopy can help differentiate from melanoma based on key features like pigment network and large globules.
Reference Gallery:
Special-site naevi of the breast. Clinical characteristics of breast naevi.
Special-site naevus of the groin. A nested and discohesive pattern is present with irregular junctional nests.
Special-site naevus of the umbilicus. Irregular nesting arrangement is present with a dyscohesive pattern, junctional cytological atypia, slight pagetoid spread, and dermal fibroplasia.

Q: A Spitz Nevus typically presents clinically as a rapidly growing, reddish-pink papule or nodule, and histologically features symmetrical nests of large [...] melanocytes.
Spitz naevus with HRAS mutation. Enlarged spindled and epithelioid melanocytes are present in the epidermis, with clefting around them. Within the dermis below, nests and cords of similar melanocytes are present between desmoplastic collagen bundles.
Spitz naevus. Small well-defined symmetrical dome-shaped tumour with uniform reddish-pink colour.
A: epithelioid and/or spindled
Back Extra: Spitz Nevus
- Clinical: Spitz naevi typically arise as pink papules or nodules and undergo a period of rapid growth lasting 3–6 months before stabilizing.
- Micro: Spitz naevi are usually symmetrical with nests of large epithelioid and/or spindled melanocytes, often showing clefting and a hyperplastic epidermis.
- Ancillary: Most Spitz naevi strongly express p16 and retain expression in a diffuse or mosaic pattern, with a low Ki-67 proliferation index.
Reference Gallery:
Spitz naevus with HRAS mutation. Enlarged spindled and epithelioid melanocytes are present in the epidermis, with clefting around them. Within the dermis below, nests and cords of similar melanocytes are present between desmoplastic collagen bundles.
Spitz naevus with HRAS mutation. This naevus measures 9 mm in diameter and 1.6 mm in thickness. Note the predominantly intradermal distribution of melanocytes, with only slight epidermal hyperplasia.
Compound Spitz naevus. Compound Spitz naevus with ALK fusion exhibits fascicular dermal growth pattern (haematoxylin phloxine saffron).
Compound Spitz naevus. This naevus with ALK fusion shows junctional nests of large spindled melanocytes, as well as intradermal nests and fascicles of spindled, amelanotic melanocytes with a fibrous background (haematoxylin phloxine saffron).
Compound Spitz naevus. This Spitz naevus with ALK fusion exhibits dermal nests and fascicles of spindled, amelanotic melanocytes with a fibrous background (haematoxylin phloxine saffron).
Spitz naevus. Small well-defined symmetrical dome-shaped tumour with uniform reddish-pink colour.
Spitz naevus. Note uniformity of lesion with dermoscopy.
Spitz naevus. Dermoscopic features.
Spitz naevus. Clinical features.

Q: Histologically, the junctional nests in a Spitz Nevus often exhibit characteristic prominent [...] separating the large melanocytes from the adjacent hyperplastic epidermis.
Spitz naevus with HRAS mutation. Enlarged spindled and epithelioid melanocytes are present in the epidermis, with clefting around them. Within the dermis below, nests and cords of similar melanocytes are present between desmoplastic collagen bundles.
A: clefting
Back Extra: Spitz Nevus
- Clinical: Spitz naevi typically arise as pink papules or nodules and undergo a period of rapid growth lasting 3–6 months before stabilizing.
- Micro: Spitz naevi are usually symmetrical with nests of large epithelioid and/or spindled melanocytes, often showing clefting and a hyperplastic epidermis.
- Ancillary: Most Spitz naevi strongly express p16 and retain expression in a diffuse or mosaic pattern, with a low Ki-67 proliferation index.
Reference Gallery:
Spitz naevus with HRAS mutation. Enlarged spindled and epithelioid melanocytes are present in the epidermis, with clefting around them. Within the dermis below, nests and cords of similar melanocytes are present between desmoplastic collagen bundles.
Spitz naevus with HRAS mutation. This naevus measures 9 mm in diameter and 1.6 mm in thickness. Note the predominantly intradermal distribution of melanocytes, with only slight epidermal hyperplasia.
Compound Spitz naevus. Compound Spitz naevus with ALK fusion exhibits fascicular dermal growth pattern (haematoxylin phloxine saffron).
Compound Spitz naevus. This naevus with ALK fusion shows junctional nests of large spindled melanocytes, as well as intradermal nests and fascicles of spindled, amelanotic melanocytes with a fibrous background (haematoxylin phloxine saffron).
Compound Spitz naevus. This Spitz naevus with ALK fusion exhibits dermal nests and fascicles of spindled, amelanotic melanocytes with a fibrous background (haematoxylin phloxine saffron).
Spitz naevus. Small well-defined symmetrical dome-shaped tumour with uniform reddish-pink colour.
Spitz naevus. Note uniformity of lesion with dermoscopy.
Spitz naevus. Dermoscopic features.
Spitz naevus. Clinical features.

Q: On dermoscopy, Pigmented Spindle Cell Nevi (Reed Nevi) classically display a [...] appearance characterized by radial lines and pseudopods at the periphery of the heavily pigmented lesion.
Pigmented spindle cell naevus (Reed naevus). The naevus is discrete and well-defined, with uniform brown-black coloration.
Pigmented spindle cell naevus (Reed naevus). Dermoscopic features. Note starburst appearance with radial lines and pseudopods at periphery.
A: starburst
Back Extra: Pigmented Spindle Cell Nevi (Reed Nevi)
- Clinical: Pigmented Spindle Cell Nevi (Reed Nevi) typically present as well-circumscribed, symmetrical, black or dark-brown macules or papules, averaging about 3 mm in diameter.
- Micro: Histologically, PSCNs show nested proliferations of spindled and pigmented melanocytes, with overlying epidermal hyperplasia and Kamino bodies.
- Ancillary: PSCNs often demonstrate strong p16 expression, and molecular analyses may reveal genomic rearrangements involving NTRK3, MET, ROS1, or RET.
Reference Gallery:
Pigmented spindle cell naevus (Reed naevus). A 3 mm pigmented macule showing epidermal hyperplasia with fascicles of bland pigmented spindle cells along the dermoepidermal junction. Clefting spaces are noted. Prominent melanophages are seen in the papillary dermis.
Pigmented spindle cell naevus (Reed naevus). The naevus is discrete and well-defined, with uniform brown-black coloration.
Pigmented spindle cell naevus (Reed naevus). Dermoscopic features. Note starburst appearance with radial lines and pseudopods at periphery.
Atypical pigmented spindle cell tumour. The lesion is represented by a combination of nests of pigmented spindle cells with uniformly distributed single pagetoid melanocytes.

Q: Histologically, Pigmented Spindle Cell Nevi (Reed Nevi) feature epidermal hyperplasia and discrete fascicles of highly pigmented, bland [...] melanocytes localized predominantly along the dermoepidermal junction, often with prominent clefting.
Pigmented spindle cell naevus (Reed naevus). A 3 mm pigmented macule showing epidermal hyperplasia with fascicles of bland pigmented spindle cells along the dermoepidermal junction. Clefting spaces are noted. Prominent melanophages are seen in the papillary dermis.
A: spindled
Back Extra: Pigmented Spindle Cell Nevi (Reed Nevi)
- Clinical: Pigmented Spindle Cell Nevi (Reed Nevi) typically present as well-circumscribed, symmetrical, black or dark-brown macules or papules, averaging about 3 mm in diameter.
- Micro: Histologically, PSCNs show nested proliferations of spindled and pigmented melanocytes, with overlying epidermal hyperplasia and Kamino bodies.
- Ancillary: PSCNs often demonstrate strong p16 expression, and molecular analyses may reveal genomic rearrangements involving NTRK3, MET, ROS1, or RET.
Reference Gallery:
Pigmented spindle cell naevus (Reed naevus). A 3 mm pigmented macule showing epidermal hyperplasia with fascicles of bland pigmented spindle cells along the dermoepidermal junction. Clefting spaces are noted. Prominent melanophages are seen in the papillary dermis.
Pigmented spindle cell naevus (Reed naevus). The naevus is discrete and well-defined, with uniform brown-black coloration.
Pigmented spindle cell naevus (Reed naevus). Dermoscopic features. Note starburst appearance with radial lines and pseudopods at periphery.
Atypical pigmented spindle cell tumour. The lesion is represented by a combination of nests of pigmented spindle cells with uniformly distributed single pagetoid melanocytes.

Q: Clinically presenting as unilateral, irregularly shaped, pigmented macules or patches that are larger and less circumscribed than conjunctival nevi, [...] often exhibit a waxing and waning course.
Conjunctival melanocytic intraepithelial lesion, early. Uniform tan macular lesion involving bulbar conjunctiva.
Conjunctival melanocytic intraepithelial lesion, advanced. Large variegated macular lesion involving bulbar conjunctiva with irregular scalloped borders and variegated tan, brown, dark-brown coloration.
A: Conjunctival Melanocytic Intraepithelial Lesions
Back Extra: Conjunctival Melanocytic Intraepithelial Lesions
- Clinical: Conjunctival Melanocytic Intraepithelial Lesions (C-MILs) are usually unilateral, irregularly shaped, pigmented macules or patches, and may wax and wane. They are larger and less circumscribed than conjunctival naevi.
- Micro: C-MILs are characterized by an intraepithelial proliferation of conjunctival melanocytes with varying degrees of cytological atypia, ranging from small melanocytes with nuclear hyperchromasia to severely atypical large pleomorphic cells.
- Ancillary: Immunohistochemistry is positive for melan-A, S100, HMB45, MITF, and SOX10. FISH for imbalances of loci such as RREB1, MYB, and CCND1 can be useful in difficult cases.
Reference Gallery:
Primary acquired melanosis with atypia. An example presenting as a flat, variably pigmented lesion in the bulbar conjunctiva and limbus.
Primary acquired melanosis with atypia. A lentiginous proliferation of melanocytes highlighted by melan-A immunostaining (inset).
Conjunctival melanocytic intraepithelial neoplasia scoring. Conjunctival melanocytic intraepithelial neoplasia is scored out of 10 on the basis of the extent of horizontal (radial) spread and vertical spread (suprabasilar extension) of melanocytes, as well as the degree of atypia. sq., squamous.
Conjunctival melanocytic intraepithelial lesion, early. Uniform tan macular lesion involving bulbar conjunctiva.
Conjunctival melanocytic intraepithelial lesion, low grade. The basilar melanocytes are increased in frequency and associated with basal-layer hyperpigmentation. The melanocytes exhibit mild variation in nuclear characteristics (haematoxylin eosin saffron stain).
Conjunctival melanocytic intraepithelial lesion, high grade. Confluence of atypical melanocytes replacing the basilar layers to lower half of the conjunctival epithelium. Focal pagetoid spread is seen (haematoxylin eosin saffron stain).
Conjunctival melanocytic intraepithelial lesion, advanced. Large variegated macular lesion involving bulbar conjunctiva with irregular scalloped borders and variegated tan, brown, dark-brown coloration.
Hypermelanosis. Basal-layer hyperpigmentation of the conjunctival epithelium is present. However, the basilar melanocytes are not increased in frequency, and cytological atypia is not observed.

Q: Microscopically, high-grade Conjunctival Melanocytic Intraepithelial Lesions are characterized by a confluence of atypical melanocytes replacing the basilar layers, often accompanied by focal [...] into the upper conjunctival epithelium.
Conjunctival melanocytic intraepithelial lesion, high grade. Confluence of atypical melanocytes replacing the basilar layers to lower half of the conjunctival epithelium. Focal pagetoid spread is seen (haematoxylin eosin saffron stain).
A: pagetoid spread
Back Extra: Conjunctival Melanocytic Intraepithelial Lesions
- Clinical: Conjunctival Melanocytic Intraepithelial Lesions (C-MILs) are usually unilateral, irregularly shaped, pigmented macules or patches, and may wax and wane. They are larger and less circumscribed than conjunctival naevi.
- Micro: C-MILs are characterized by an intraepithelial proliferation of conjunctival melanocytes with varying degrees of cytological atypia, ranging from small melanocytes with nuclear hyperchromasia to severely atypical large pleomorphic cells.
- Ancillary: Immunohistochemistry is positive for melan-A, S100, HMB45, MITF, and SOX10. FISH for imbalances of loci such as RREB1, MYB, and CCND1 can be useful in difficult cases.
Reference Gallery:
Primary acquired melanosis with atypia. An example presenting as a flat, variably pigmented lesion in the bulbar conjunctiva and limbus.
Primary acquired melanosis with atypia. A lentiginous proliferation of melanocytes highlighted by melan-A immunostaining (inset).
Conjunctival melanocytic intraepithelial neoplasia scoring. Conjunctival melanocytic intraepithelial neoplasia is scored out of 10 on the basis of the extent of horizontal (radial) spread and vertical spread (suprabasilar extension) of melanocytes, as well as the degree of atypia. sq., squamous.
Conjunctival melanocytic intraepithelial lesion, early. Uniform tan macular lesion involving bulbar conjunctiva.
Conjunctival melanocytic intraepithelial lesion, low grade. The basilar melanocytes are increased in frequency and associated with basal-layer hyperpigmentation. The melanocytes exhibit mild variation in nuclear characteristics (haematoxylin eosin saffron stain).
Conjunctival melanocytic intraepithelial lesion, high grade. Confluence of atypical melanocytes replacing the basilar layers to lower half of the conjunctival epithelium. Focal pagetoid spread is seen (haematoxylin eosin saffron stain).
Conjunctival melanocytic intraepithelial lesion, advanced. Large variegated macular lesion involving bulbar conjunctiva with irregular scalloped borders and variegated tan, brown, dark-brown coloration.
Hypermelanosis. Basal-layer hyperpigmentation of the conjunctival epithelium is present. However, the basilar melanocytes are not increased in frequency, and cytological atypia is not observed.

Q: In Conjunctival Melanocytic Intraepithelial Lesions, the characteristic lentiginous intraepithelial proliferation of atypical melanocytes is reliably highlighted by immunohistochemical markers such as S100, SOX10, HMB45, and [...].
Primary acquired melanosis with atypia. A lentiginous proliferation of melanocytes highlighted by melan-A immunostaining (inset).
A: melan-A
Back Extra: Conjunctival Melanocytic Intraepithelial Lesions
- Clinical: Conjunctival Melanocytic Intraepithelial Lesions (C-MILs) are usually unilateral, irregularly shaped, pigmented macules or patches, and may wax and wane. They are larger and less circumscribed than conjunctival naevi.
- Micro: C-MILs are characterized by an intraepithelial proliferation of conjunctival melanocytes with varying degrees of cytological atypia, ranging from small melanocytes with nuclear hyperchromasia to severely atypical large pleomorphic cells.
- Ancillary: Immunohistochemistry is positive for melan-A, S100, HMB45, MITF, and SOX10. FISH for imbalances of loci such as RREB1, MYB, and CCND1 can be useful in difficult cases.
Reference Gallery:
Primary acquired melanosis with atypia. An example presenting as a flat, variably pigmented lesion in the bulbar conjunctiva and limbus.
Primary acquired melanosis with atypia. A lentiginous proliferation of melanocytes highlighted by melan-A immunostaining (inset).
Conjunctival melanocytic intraepithelial neoplasia scoring. Conjunctival melanocytic intraepithelial neoplasia is scored out of 10 on the basis of the extent of horizontal (radial) spread and vertical spread (suprabasilar extension) of melanocytes, as well as the degree of atypia. sq., squamous.
Conjunctival melanocytic intraepithelial lesion, early. Uniform tan macular lesion involving bulbar conjunctiva.
Conjunctival melanocytic intraepithelial lesion, low grade. The basilar melanocytes are increased in frequency and associated with basal-layer hyperpigmentation. The melanocytes exhibit mild variation in nuclear characteristics (haematoxylin eosin saffron stain).
Conjunctival melanocytic intraepithelial lesion, high grade. Confluence of atypical melanocytes replacing the basilar layers to lower half of the conjunctival epithelium. Focal pagetoid spread is seen (haematoxylin eosin saffron stain).
Conjunctival melanocytic intraepithelial lesion, advanced. Large variegated macular lesion involving bulbar conjunctiva with irregular scalloped borders and variegated tan, brown, dark-brown coloration.
Hypermelanosis. Basal-layer hyperpigmentation of the conjunctival epithelium is present. However, the basilar melanocytes are not increased in frequency, and cytological atypia is not observed.

Q: An asymmetrical, poorly circumscribed dermal proliferation of large epithelioid to spindled melanocytes that shows little to no maturation and a pushing lower border is characteristic of a(n) [...].
Spitz melanocytoma (atypical Spitz tumour). A compound melanocytic proliferation with asymmetry, poor circumscription, pseudoepitheliomatous hyperplasia, and no ulceration, developing in a paediatric patient.
Spitz melanocytoma (atypical Spitz tumour). Nests of large monomorphic epithelioid cells with enlarged rounded nuclei, relatively prominent nucleoli, abundant cytoplasm, occasional mitotic figures, and an inflammatory cell reaction. This tumour harboured a MAP3K8 fusion and a homozygous deletion of CDKN2A. No TERT promoter mutation was detected.
A: Spitz Melanocytoma (Atypical Spitz Tumour)
Back Extra: Spitz Melanocytoma (Atypical Spitz Tumour)
- Clinical: Spitz melanocytomas typically appear as papules, nodules, or plaques ≥ 5 mm in diameter, and they may display asymmetry, irregular borders, color variegation, and/or ulceration. They are most common in adolescents and young adults.
- Micro: Spitz melanocytomas often arise as asymmetrical, poorly circumscribed proliferations of large epithelioid to spindled melanocytes, arranged as cellular aggregates or nodules that replace the dermis, with little or no maturation and a pushing lower border.
- Ancillary: Identification of a Spitz initiating oncogene is helpful in confirming Spitz lineage. Complete absence of p16 expression is associated with genetic inactivation of CDKN2A, which does not occur in Spitz naevi.
Reference Gallery:
Spitz melanocytoma (atypical Spitz tumour). A compound melanocytic proliferation with asymmetry, poor circumscription, pseudoepitheliomatous hyperplasia, and no ulceration, developing in a paediatric patient.
Spitz melanocytoma (atypical Spitz tumour). Nests of large monomorphic epithelioid cells with enlarged rounded nuclei, relatively prominent nucleoli, abundant cytoplasm, occasional mitotic figures, and an inflammatory cell reaction. This tumour harboured a MAP3K8 fusion and a homozygous deletion of CDKN2A. No TERT promoter mutation was detected.
Spitz melanocytoma (atypical Spitz tumour). This Spitz melanocytoma has a BRAF fusion and homozygous deletion of CDKN2A. It is exophytic with a slightly asymmetrical distribution of melanocytes and a patchy lymphocytic infiltrate.
Spitz melanocytoma (atypical Spitz tumour). This tumour with BRAF fusion shows epidermal hyperplasia and large aggregates of epithelioid to fusiform melanocytes in the superficial dermis.
Spitz melanocytoma (atypical Spitz tumour). Tumour with BRAF fusion. The melanocytes have variably sized nuclei and abundant cytoplasm. Some nuclei have intranuclear vacuoles and show hyperchromasia.
Spitz melanocytoma (atypical Spitz tumour). Tumour with BRAF fusion. Immunohistochemistry for p16 demonstrates a small residuum of Spitz naevus that retains p16 expression. Absence of p16 expression in the remainder of the tumour is in keeping with deep deletion of CDKN2A.
Spitz melanocytoma (atypical Spitz tumour). Growing nodule on the knee with irregular pigmentation (MAP3K8 fusion).
Spitz melanocytoma. There is a loss of expression of p16 by tumour cells.

Q: In Spitz Melanocytoma (Atypical Spitz Tumour), immunohistochemical loss of [...] expression is frequently observed, which correlates with the genetic inactivation or deep deletion of CDKN2A and helps distinguish it from a benign Spitz nevus.
Spitz melanocytoma (atypical Spitz tumour). Tumour with BRAF fusion. Immunohistochemistry for p16 demonstrates a small residuum of Spitz naevus that retains p16 expression. Absence of p16 expression in the remainder of the tumour is in keeping with deep deletion of CDKN2A.
Spitz melanocytoma. There is a loss of expression of p16 by tumour cells.
A: p16
Back Extra: Spitz Melanocytoma (Atypical Spitz Tumour)
- Clinical: Spitz melanocytomas typically appear as papules, nodules, or plaques ≥ 5 mm in diameter, and they may display asymmetry, irregular borders, color variegation, and/or ulceration. They are most common in adolescents and young adults.
- Micro: Spitz melanocytomas often arise as asymmetrical, poorly circumscribed proliferations of large epithelioid to spindled melanocytes, arranged as cellular aggregates or nodules that replace the dermis, with little or no maturation and a pushing lower border.
- Ancillary: Identification of a Spitz initiating oncogene is helpful in confirming Spitz lineage. Complete absence of p16 expression is associated with genetic inactivation of CDKN2A, which does not occur in Spitz naevi.
Reference Gallery:
Spitz melanocytoma (atypical Spitz tumour). A compound melanocytic proliferation with asymmetry, poor circumscription, pseudoepitheliomatous hyperplasia, and no ulceration, developing in a paediatric patient.
Spitz melanocytoma (atypical Spitz tumour). Nests of large monomorphic epithelioid cells with enlarged rounded nuclei, relatively prominent nucleoli, abundant cytoplasm, occasional mitotic figures, and an inflammatory cell reaction. This tumour harboured a MAP3K8 fusion and a homozygous deletion of CDKN2A. No TERT promoter mutation was detected.
Spitz melanocytoma (atypical Spitz tumour). This Spitz melanocytoma has a BRAF fusion and homozygous deletion of CDKN2A. It is exophytic with a slightly asymmetrical distribution of melanocytes and a patchy lymphocytic infiltrate.
Spitz melanocytoma (atypical Spitz tumour). This tumour with BRAF fusion shows epidermal hyperplasia and large aggregates of epithelioid to fusiform melanocytes in the superficial dermis.
Spitz melanocytoma (atypical Spitz tumour). Tumour with BRAF fusion. The melanocytes have variably sized nuclei and abundant cytoplasm. Some nuclei have intranuclear vacuoles and show hyperchromasia.
Spitz melanocytoma (atypical Spitz tumour). Tumour with BRAF fusion. Immunohistochemistry for p16 demonstrates a small residuum of Spitz naevus that retains p16 expression. Absence of p16 expression in the remainder of the tumour is in keeping with deep deletion of CDKN2A.
Spitz melanocytoma (atypical Spitz tumour). Growing nodule on the knee with irregular pigmentation (MAP3K8 fusion).
Spitz melanocytoma. There is a loss of expression of p16 by tumour cells.

Q: A newly growing, irregularly pigmented nodule in an adolescent that demonstrates large, epithelioid melanocytes harboring MAP3K8 or BRAF fusions is characteristic of a(n) [...].
Spitz melanocytoma (atypical Spitz tumour). This Spitz melanocytoma has a BRAF fusion and homozygous deletion of CDKN2A. It is exophytic with a slightly asymmetrical distribution of melanocytes and a patchy lymphocytic infiltrate.
Spitz melanocytoma (atypical Spitz tumour). Growing nodule on the knee with irregular pigmentation (MAP3K8 fusion).
A: Spitz Melanocytoma (Atypical Spitz Tumour)
Back Extra: Spitz Melanocytoma (Atypical Spitz Tumour)
- Clinical: Spitz melanocytomas typically appear as papules, nodules, or plaques ≥ 5 mm in diameter, and they may display asymmetry, irregular borders, color variegation, and/or ulceration. They are most common in adolescents and young adults.
- Micro: Spitz melanocytomas often arise as asymmetrical, poorly circumscribed proliferations of large epithelioid to spindled melanocytes, arranged as cellular aggregates or nodules that replace the dermis, with little or no maturation and a pushing lower border.
- Ancillary: Identification of a Spitz initiating oncogene is helpful in confirming Spitz lineage. Complete absence of p16 expression is associated with genetic inactivation of CDKN2A, which does not occur in Spitz naevi.
Reference Gallery:
Spitz melanocytoma (atypical Spitz tumour). A compound melanocytic proliferation with asymmetry, poor circumscription, pseudoepitheliomatous hyperplasia, and no ulceration, developing in a paediatric patient.
Spitz melanocytoma (atypical Spitz tumour). Nests of large monomorphic epithelioid cells with enlarged rounded nuclei, relatively prominent nucleoli, abundant cytoplasm, occasional mitotic figures, and an inflammatory cell reaction. This tumour harboured a MAP3K8 fusion and a homozygous deletion of CDKN2A. No TERT promoter mutation was detected.
Spitz melanocytoma (atypical Spitz tumour). This Spitz melanocytoma has a BRAF fusion and homozygous deletion of CDKN2A. It is exophytic with a slightly asymmetrical distribution of melanocytes and a patchy lymphocytic infiltrate.
Spitz melanocytoma (atypical Spitz tumour). This tumour with BRAF fusion shows epidermal hyperplasia and large aggregates of epithelioid to fusiform melanocytes in the superficial dermis.
Spitz melanocytoma (atypical Spitz tumour). Tumour with BRAF fusion. The melanocytes have variably sized nuclei and abundant cytoplasm. Some nuclei have intranuclear vacuoles and show hyperchromasia.
Spitz melanocytoma (atypical Spitz tumour). Tumour with BRAF fusion. Immunohistochemistry for p16 demonstrates a small residuum of Spitz naevus that retains p16 expression. Absence of p16 expression in the remainder of the tumour is in keeping with deep deletion of CDKN2A.
Spitz melanocytoma (atypical Spitz tumour). Growing nodule on the knee with irregular pigmentation (MAP3K8 fusion).
Spitz melanocytoma. There is a loss of expression of p16 by tumour cells.

Q: The melanocytic tumor characterized microscopically by a heavily pigmented, predominantly dermal proliferation of dendritic and epithelioid melanocytes (often displaying "fried-egg" nuclei) interspersed among abundant melanophages is known as [...].
Pigmented epithelioid melanocytoma. Fascicles of epithelioid cells are visible in the upper left, with “fried-egg nuclei” (oval nuclei with a large central nucleolus and thickened nuclear membrane). Nest of common naevus is present in the lower right. Sheets of melanophages predominate overall (haematoxylin phloxine saffron).
Pigmented epithelioid melanocytoma, MAP3K8 fusion genetic background. Dermal nests and isolated midsized epithelioid melanocytes are surrounded by numerous melanophages (haematoxylin eosin saffron).
A: Pigmented Epithelioid Melanocytoma
Back Extra: Pigmented Epithelioid Melanocytoma
- Clinical: Pigmented epithelioid melanocytomas (PEMs) appear as slowly growing pigmented nodules or papules, most commonly arising in the second and third decades of life.
- Micro: PEMs are heavily pigmented, predominantly dermal tumours with an inverted wedge or bulbous configuration, composed of pigmented dendritic and epithelioid melanocytes.
- Ancillary: Loss of PRKAR1A expression is found in up to 80% of cases, and DNA- and RNA-based sequencing helps confirm the diagnosis and rule out molecular markers of progression towards melanoma.
Reference Gallery:
Pigmented epithelioid melanocytoma. A slowly growing pigmented nodule.
Pigmented epithelioid melanocytoma. Small hyperpigmented superficial dermal nodule. Thin fascicles of spindled melanocytes are visible between the predominating sheets of melanophages (haematoxylin phloxine saffron stain).
Pigmented epithelioid melanocytoma. Fascicles of epithelioid cells are visible in the upper left, with “fried-egg nuclei” (oval nuclei with a large central nucleolus and thickened nuclear membrane). Nest of common naevus is present in the lower right. Sheets of melanophages predominate overall (haematoxylin phloxine saffron).
Pigmented epithelioid melanocytoma, MAP3K8 fusion genetic background. Compound melanocytic proliferation characterized by a slight epidermal hyperplasia with pigmented junction and a hyperpigmented dermal infiltration with ill-limited fascicles in a fibrous background (haematoxylin phloxine saffron).
Pigmented epithelioid melanocytoma, MAP3K8 fusion genetic background. Dermal nests and isolated midsized epithelioid melanocytes are surrounded by numerous melanophages (haematoxylin eosin saffron).
Pigmented epithelioid melanocytoma. PRKAR1A immunohistochemistry. The common naevus and melanophages display a diffuse cytoplasmic staining. The fascicles of epithelioid cells lack cytoplasmic staining.

Q: Up to 80% of cases of Pigmented Epithelioid Melanocytoma demonstrate an immunohistochemical loss of [...] expression.
Pigmented epithelioid melanocytoma. PRKAR1A immunohistochemistry. The common naevus and melanophages display a diffuse cytoplasmic staining. The fascicles of epithelioid cells lack cytoplasmic staining.
A: PRKAR1A
Back Extra: Pigmented Epithelioid Melanocytoma
- Clinical: Pigmented epithelioid melanocytomas (PEMs) appear as slowly growing pigmented nodules or papules, most commonly arising in the second and third decades of life.
- Micro: PEMs are heavily pigmented, predominantly dermal tumours with an inverted wedge or bulbous configuration, composed of pigmented dendritic and epithelioid melanocytes.
- Ancillary: Loss of PRKAR1A expression is found in up to 80% of cases, and DNA- and RNA-based sequencing helps confirm the diagnosis and rule out molecular markers of progression towards melanoma.
Reference Gallery:
Pigmented epithelioid melanocytoma. A slowly growing pigmented nodule.
Pigmented epithelioid melanocytoma. Small hyperpigmented superficial dermal nodule. Thin fascicles of spindled melanocytes are visible between the predominating sheets of melanophages (haematoxylin phloxine saffron stain).
Pigmented epithelioid melanocytoma. Fascicles of epithelioid cells are visible in the upper left, with “fried-egg nuclei” (oval nuclei with a large central nucleolus and thickened nuclear membrane). Nest of common naevus is present in the lower right. Sheets of melanophages predominate overall (haematoxylin phloxine saffron).
Pigmented epithelioid melanocytoma, MAP3K8 fusion genetic background. Compound melanocytic proliferation characterized by a slight epidermal hyperplasia with pigmented junction and a hyperpigmented dermal infiltration with ill-limited fascicles in a fibrous background (haematoxylin phloxine saffron).
Pigmented epithelioid melanocytoma, MAP3K8 fusion genetic background. Dermal nests and isolated midsized epithelioid melanocytes are surrounded by numerous melanophages (haematoxylin eosin saffron).
Pigmented epithelioid melanocytoma. PRKAR1A immunohistochemistry. The common naevus and melanophages display a diffuse cytoplasmic staining. The fascicles of epithelioid cells lack cytoplasmic staining.

Q: In Acral Melanoma on the sole, dermoscopy characteristically reveals a [...] pattern, where pigment concentrates on the ridges of the skin markings.
Acral melanoma. Dermoscopic finding. Parallel ridge pattern (brown to black band-like pigmentation on the ridges of the skin markings) is characteristic of acral melanoma on the sole.
A: parallel ridge
Back Extra: Acral Melanoma
- Clinical: Acral lentiginous melanoma (ALM) typically presents as a variably pigmented flat patch with an irregular outline, progressing to a darker papule or nodule.
- Micro: In situ ALM shows an irregularly distributed, mostly basal melanocytes with enlarged hyperchromatic nuclei and prominent dendrites, followed by dermal invasion.
- Ancillary: SOX10 immunostaining is positive in acral melanoma and can help in assessing the density and distribution of melanocytes.
Reference Gallery:
Acral melanoma. Irregular black patch with central papule on the heel of an 81-year-old woman.
Subungual melanoma. Total melanonychia of the thumbnail with apparent Hutchinson sign.
Amelanotic acral melanoma. Ulcerative erythematous nodule on the heel, without pigment.
Acral melanoma. Dermoscopic finding. Parallel ridge pattern (brown to black band-like pigmentation on the ridges of the skin markings) is characteristic of acral melanoma on the sole.
Acral lentiginous melanoma. There are a few nests and mostly lentiginous proliferation of atypical hyperchromatic melanocytes in the epidermal basal layer.
Acral melanoma. Subungual melanoma. Scattered proliferation of atypical hyperchromatic melanocytes in the nail matrix and invasive spindle cells with inflammatory cells.
Sentinel lymph node of acral melanoma. Tumour cells are not identifiable in routine H&E stain.
Sentinel lymph node of acral melanoma. SOX10 staining identifies the isolated melanoma cells in sentinel lymph node.
Acral melanoma. Immunostaining for melan-A highlights a lentiginous proliferation of atypical melanocytes with prominent dendritic processes.
Subungual melanoma. This very early stage example shows only scattered proliferation of atypical hyperchromatic melanocytes in the nail matrix.

Q: Microscopically, in situ Acral Melanoma typically demonstrates a lentiginous proliferation of atypical, hyperchromatic melanocytes with prominent [...] processes.
Acral lentiginous melanoma. There are a few nests and mostly lentiginous proliferation of atypical hyperchromatic melanocytes in the epidermal basal layer.
Acral melanoma. Immunostaining for melan-A highlights a lentiginous proliferation of atypical melanocytes with prominent dendritic processes.
A: dendritic
Back Extra: Acral Melanoma
- Clinical: Acral lentiginous melanoma (ALM) typically presents as a variably pigmented flat patch with an irregular outline, progressing to a darker papule or nodule.
- Micro: In situ ALM shows an irregularly distributed, mostly basal melanocytes with enlarged hyperchromatic nuclei and prominent dendrites, followed by dermal invasion.
- Ancillary: SOX10 immunostaining is positive in acral melanoma and can help in assessing the density and distribution of melanocytes.
Reference Gallery:
Acral melanoma. Irregular black patch with central papule on the heel of an 81-year-old woman.
Subungual melanoma. Total melanonychia of the thumbnail with apparent Hutchinson sign.
Amelanotic acral melanoma. Ulcerative erythematous nodule on the heel, without pigment.
Acral melanoma. Dermoscopic finding. Parallel ridge pattern (brown to black band-like pigmentation on the ridges of the skin markings) is characteristic of acral melanoma on the sole.
Acral lentiginous melanoma. There are a few nests and mostly lentiginous proliferation of atypical hyperchromatic melanocytes in the epidermal basal layer.
Acral melanoma. Subungual melanoma. Scattered proliferation of atypical hyperchromatic melanocytes in the nail matrix and invasive spindle cells with inflammatory cells.
Sentinel lymph node of acral melanoma. Tumour cells are not identifiable in routine H&E stain.
Sentinel lymph node of acral melanoma. SOX10 staining identifies the isolated melanoma cells in sentinel lymph node.
Acral melanoma. Immunostaining for melan-A highlights a lentiginous proliferation of atypical melanocytes with prominent dendritic processes.
Subungual melanoma. This very early stage example shows only scattered proliferation of atypical hyperchromatic melanocytes in the nail matrix.

Q: A subungual Acral Melanoma can present as total melanonychia extending from the nail bed into the proximal nail fold, a classic clinical finding known as the [...] sign.
Subungual melanoma. Total melanonychia of the thumbnail with apparent Hutchinson sign.
A: Hutchinson
Back Extra: Acral Melanoma
- Clinical: Acral lentiginous melanoma (ALM) typically presents as a variably pigmented flat patch with an irregular outline, progressing to a darker papule or nodule.
- Micro: In situ ALM shows an irregularly distributed, mostly basal melanocytes with enlarged hyperchromatic nuclei and prominent dendrites, followed by dermal invasion.
- Ancillary: SOX10 immunostaining is positive in acral melanoma and can help in assessing the density and distribution of melanocytes.
Reference Gallery:
Acral melanoma. Irregular black patch with central papule on the heel of an 81-year-old woman.
Subungual melanoma. Total melanonychia of the thumbnail with apparent Hutchinson sign.
Amelanotic acral melanoma. Ulcerative erythematous nodule on the heel, without pigment.
Acral melanoma. Dermoscopic finding. Parallel ridge pattern (brown to black band-like pigmentation on the ridges of the skin markings) is characteristic of acral melanoma on the sole.
Acral lentiginous melanoma. There are a few nests and mostly lentiginous proliferation of atypical hyperchromatic melanocytes in the epidermal basal layer.
Acral melanoma. Subungual melanoma. Scattered proliferation of atypical hyperchromatic melanocytes in the nail matrix and invasive spindle cells with inflammatory cells.
Sentinel lymph node of acral melanoma. Tumour cells are not identifiable in routine H&E stain.
Sentinel lymph node of acral melanoma. SOX10 staining identifies the isolated melanoma cells in sentinel lymph node.
Acral melanoma. Immunostaining for melan-A highlights a lentiginous proliferation of atypical melanocytes with prominent dendritic processes.
Subungual melanoma. This very early stage example shows only scattered proliferation of atypical hyperchromatic melanocytes in the nail matrix.

Q: Histologically, a sharply delimited, expansile nodule of monomorphic epithelioid cells and prominent, confluent zones of necrosis underlying a background benign melanocytic proliferation is characteristic of [...].
Dermal melanoma arising in a large congenital naevus. A sharply delimited rounded nodule of melanoma underlies the congenital naevus in the superficial dermis.
Dermal melanoma arising in a large congenital naevus. A monomorphic population of epithelioid melanoma cells is seen in this field.
Melanoma arising in large congenital naevus. Large confluent zones of necrosis are present.
A: Melanoma arising in giant congenital naevus
Back Extra: Melanoma arising in giant congenital naevus
- Clinical: Melanomas arising in giant congenital naevi are rapidly growing, often ulcerated nodules or plaques that differ in colour and texture from the congenital naevus in the background.
- Micro: Melanoma cells can appear as large expansile nodules with sharp circumscription, necrosis, and mitoses. Cytomorphological features may include epithelioid cells with hyperchromatic nuclei and prominent nucleoli.
- Ancillary: PRAME positivity, loss of p16 and H3 p.K27me3 immunoreactivity, and increased Ki-67 labelling favour melanoma. Copy-number analysis typically shows gains and losses of arms or segments of chromosomes.
Reference Gallery:
Dermal melanoma arising in a large congenital naevus. A sharply delimited rounded nodule of melanoma underlies the congenital naevus in the superficial dermis.
Dermal melanoma arising in a large congenital naevus. A monomorphic population of epithelioid melanoma cells is seen in this field.
Melanoma arising in large congenital naevus. Large confluent zones of necrosis are present.
Melanoma arising in giant congenital naevus presenting as a reddish brown nodule (arrow). Legend text not found
Melanoma arising in a large congenital naevus. Sheet-like arrangements of poorly differentiated polygonal melanoma cells are seen in this field.

Q: Clinically presenting as a rapidly growing, reddish-brown nodule that distinctly differs in color and texture from the background pigmented lesion, the image displays a classic case of [...].
Melanoma arising in giant congenital naevus presenting as a reddish brown nodule (arrow). Legend text not found
A: Melanoma arising in giant congenital naevus
Back Extra: Melanoma arising in giant congenital naevus
- Clinical: Melanomas arising in giant congenital naevi are rapidly growing, often ulcerated nodules or plaques that differ in colour and texture from the congenital naevus in the background.
- Micro: Melanoma cells can appear as large expansile nodules with sharp circumscription, necrosis, and mitoses. Cytomorphological features may include epithelioid cells with hyperchromatic nuclei and prominent nucleoli.
- Ancillary: PRAME positivity, loss of p16 and H3 p.K27me3 immunoreactivity, and increased Ki-67 labelling favour melanoma. Copy-number analysis typically shows gains and losses of arms or segments of chromosomes.
Reference Gallery:
Dermal melanoma arising in a large congenital naevus. A sharply delimited rounded nodule of melanoma underlies the congenital naevus in the superficial dermis.
Dermal melanoma arising in a large congenital naevus. A monomorphic population of epithelioid melanoma cells is seen in this field.
Melanoma arising in large congenital naevus. Large confluent zones of necrosis are present.
Melanoma arising in giant congenital naevus presenting as a reddish brown nodule (arrow). Legend text not found
Melanoma arising in a large congenital naevus. Sheet-like arrangements of poorly differentiated polygonal melanoma cells are seen in this field.

Q: A deeply pigmented tumor demonstrating an abrupt histologic transition from a benign intraseptal proliferation of small spindled cells to a malignant nodule of highly atypical epithelioid melanocytes with brisk mitoses and central necrosis is diagnostic of [...].
Melanoma arising in blue naevus. Dense sheet-like, pigmented multilobular tumour with central area of necrosis. The tumour extends into subcutaneous tissue, with well-defined lowermost margin.
Melanoma arising in blue naevus. Large tumoural nodule connected to a fibrous, pigmented, intraseptal melanocytic proliferation in the subcutis (haematoxylin eosin saffron stain).
Melanoma arising in blue naevus. Higher-magnification view showing sheets of large epithelioid melanocytes with multiple mitoses in the malignant area (right side), adjacent to small spindled melanocytes (haematoxylin eosin saffron stain).
A: Melanoma arising in blue naevus
Back Extra: Melanoma arising in blue naevus
- Clinical: Melanoma arising in blue naevus (MBN) is a fast-growing, large nodule, usually in a longstanding blue naevus, most common in adults aged > 45 years, with no sex predilection. The scalp is the most common site.
- Micro: MBN shows dense dermal sheets of large spindled and epithelioid melanocytes with severe atypia and high mitotic activity, often effacing adnexal structures, and frequent central areas of necrosis in large tumours.
- Ancillary: MBNs harbour GNAQ, GNA11, PLCB4, or CYSLTR2 mutations, and mutations of SF3B1, EIF1AX, or BAP1 can support the diagnosis of malignant transformation.
Reference Gallery:
Melanoma arising in blue naevus. Dense sheet-like, pigmented multilobular tumour with central area of necrosis. The tumour extends into subcutaneous tissue, with well-defined lowermost margin.
Melanoma arising in blue naevus. Large tumoural nodule connected to a fibrous, pigmented, intraseptal melanocytic proliferation in the subcutis (haematoxylin eosin saffron stain).
Melanoma arising in blue naevus. Higher-magnification view showing sheets of large epithelioid melanocytes with multiple mitoses in the malignant area (right side), adjacent to small spindled melanocytes (haematoxylin eosin saffron stain).

Q: In Melanoma arising in blue naevus, the malignant transformation is microscopically characterized by an abrupt transition to dense dermal sheets of severely atypical spindled and [...] melanocytes that exhibit high mitotic activity.
Melanoma arising in blue naevus. Higher-magnification view showing sheets of large epithelioid melanocytes with multiple mitoses in the malignant area (right side), adjacent to small spindled melanocytes (haematoxylin eosin saffron stain).
A: epithelioid
Back Extra: Melanoma arising in blue naevus
- Clinical: Melanoma arising in blue naevus (MBN) is a fast-growing, large nodule, usually in a longstanding blue naevus, most common in adults aged > 45 years, with no sex predilection. The scalp is the most common site.
- Micro: MBN shows dense dermal sheets of large spindled and epithelioid melanocytes with severe atypia and high mitotic activity, often effacing adnexal structures, and frequent central areas of necrosis in large tumours.
- Ancillary: MBNs harbour GNAQ, GNA11, PLCB4, or CYSLTR2 mutations, and mutations of SF3B1, EIF1AX, or BAP1 can support the diagnosis of malignant transformation.
Reference Gallery:
Melanoma arising in blue naevus. Dense sheet-like, pigmented multilobular tumour with central area of necrosis. The tumour extends into subcutaneous tissue, with well-defined lowermost margin.
Melanoma arising in blue naevus. Large tumoural nodule connected to a fibrous, pigmented, intraseptal melanocytic proliferation in the subcutis (haematoxylin eosin saffron stain).
Melanoma arising in blue naevus. Higher-magnification view showing sheets of large epithelioid melanocytes with multiple mitoses in the malignant area (right side), adjacent to small spindled melanocytes (haematoxylin eosin saffron stain).

Q: Macroscopically and on low-power examination, the large malignant nodules of Melanoma arising in blue naevus typically present as dense, multilobular pigmented tumors extending into the subcutis that frequently exhibit areas of central [...].
Melanoma arising in blue naevus. Dense sheet-like, pigmented multilobular tumour with central area of necrosis. The tumour extends into subcutaneous tissue, with well-defined lowermost margin.
A: necrosis
Back Extra: Melanoma arising in blue naevus
- Clinical: Melanoma arising in blue naevus (MBN) is a fast-growing, large nodule, usually in a longstanding blue naevus, most common in adults aged > 45 years, with no sex predilection. The scalp is the most common site.
- Micro: MBN shows dense dermal sheets of large spindled and epithelioid melanocytes with severe atypia and high mitotic activity, often effacing adnexal structures, and frequent central areas of necrosis in large tumours.
- Ancillary: MBNs harbour GNAQ, GNA11, PLCB4, or CYSLTR2 mutations, and mutations of SF3B1, EIF1AX, or BAP1 can support the diagnosis of malignant transformation.
Reference Gallery:
Melanoma arising in blue naevus. Dense sheet-like, pigmented multilobular tumour with central area of necrosis. The tumour extends into subcutaneous tissue, with well-defined lowermost margin.
Melanoma arising in blue naevus. Large tumoural nodule connected to a fibrous, pigmented, intraseptal melanocytic proliferation in the subcutis (haematoxylin eosin saffron stain).
Melanoma arising in blue naevus. Higher-magnification view showing sheets of large epithelioid melanocytes with multiple mitoses in the malignant area (right side), adjacent to small spindled melanocytes (haematoxylin eosin saffron stain).

Q: Suspicious limbal masses presenting with multifocal irregular pigmentation, tumor hemorrhage, and prominent [...] are highly characteristic clinical features of Conjunctival Melanoma.
Conjunctival melanoma. A,B Limbal masses with tortuous feeder vessels. Multifocal irregular pigmentation in Panel A. C Multinodular mass in the tarsal conjunctiva. D Aggressive recurrences can be non-pigmented.
A: tortuous feeder vessels
Back Extra: Conjunctival Melanoma
- Clinical: Conjunctival melanomas vary in appearance and can be amelanotic. Suspicious features include tumour haemorrhage, large tumour base, tortuous feeder vessels, and corneal invasion.
- Micro: Histology shows stromal invasion by nests or sheets of atypical melanocytes, with possible ulceration and mitotic activity.
- Ancillary: Molecular studies often reveal NRAS, NRAS, and TERT mutations, and nuclear expression of PRAME.
Reference Gallery:
Conjunctival melanoma. Early invasive melanoma arising in a naevus. Molecular studies revealed NRAS p.Q61R and TERT c.-146C>T mutation, positive melanoma FISH, and nuclear expression of PRAME.
Conjunctival melanoma. Early invasive melanoma arising in a naevus. Molecular studies revealed NRAS p.Q61R and TERT c.-146C>T mutation, positive melanoma FISH, and nuclear expression of PRAME.
Conjunctival melanoma. A,B Limbal masses with tortuous feeder vessels. Multifocal irregular pigmentation in Panel A. C Multinodular mass in the tarsal conjunctiva. D Aggressive recurrences can be non-pigmented.
Conjunctival melanoma. Invasive tumour with an epithelioid cell type.

Q: Microscopically, [...] is diagnosed by identifying stromal invasion by nests or sheets of atypical melanocytes, which often exhibit an epithelioid morphology and can arise from a pre-existing nevus.
Conjunctival melanoma. Early invasive melanoma arising in a naevus. Molecular studies revealed NRAS p.Q61R and TERT c.-146C>T mutation, positive melanoma FISH, and nuclear expression of PRAME.
Conjunctival melanoma. Invasive tumour with an epithelioid cell type.
A: Conjunctival Melanoma
Back Extra: Conjunctival Melanoma
- Clinical: Conjunctival melanomas vary in appearance and can be amelanotic. Suspicious features include tumour haemorrhage, large tumour base, tortuous feeder vessels, and corneal invasion.
- Micro: Histology shows stromal invasion by nests or sheets of atypical melanocytes, with possible ulceration and mitotic activity.
- Ancillary: Molecular studies often reveal NRAS, NRAS, and TERT mutations, and nuclear expression of PRAME.
Reference Gallery:
Conjunctival melanoma. Early invasive melanoma arising in a naevus. Molecular studies revealed NRAS p.Q61R and TERT c.-146C>T mutation, positive melanoma FISH, and nuclear expression of PRAME.
Conjunctival melanoma. Early invasive melanoma arising in a naevus. Molecular studies revealed NRAS p.Q61R and TERT c.-146C>T mutation, positive melanoma FISH, and nuclear expression of PRAME.
Conjunctival melanoma. A,B Limbal masses with tortuous feeder vessels. Multifocal irregular pigmentation in Panel A. C Multinodular mass in the tarsal conjunctiva. D Aggressive recurrences can be non-pigmented.
Conjunctival melanoma. Invasive tumour with an epithelioid cell type.

Q: In addition to NRAS and TERT promoter mutations, Conjunctival Melanoma frequently demonstrates diffuse nuclear positivity for the immunohistochemical marker [...].
Conjunctival melanoma. Early invasive melanoma arising in a naevus. Molecular studies revealed NRAS p.Q61R and TERT c.-146C>T mutation, positive melanoma FISH, and nuclear expression of PRAME.
A: PRAME
Back Extra: Conjunctival Melanoma
- Clinical: Conjunctival melanomas vary in appearance and can be amelanotic. Suspicious features include tumour haemorrhage, large tumour base, tortuous feeder vessels, and corneal invasion.
- Micro: Histology shows stromal invasion by nests or sheets of atypical melanocytes, with possible ulceration and mitotic activity.
- Ancillary: Molecular studies often reveal NRAS, NRAS, and TERT mutations, and nuclear expression of PRAME.
Reference Gallery:
Conjunctival melanoma. Early invasive melanoma arising in a naevus. Molecular studies revealed NRAS p.Q61R and TERT c.-146C>T mutation, positive melanoma FISH, and nuclear expression of PRAME.
Conjunctival melanoma. Early invasive melanoma arising in a naevus. Molecular studies revealed NRAS p.Q61R and TERT c.-146C>T mutation, positive melanoma FISH, and nuclear expression of PRAME.
Conjunctival melanoma. A,B Limbal masses with tortuous feeder vessels. Multifocal irregular pigmentation in Panel A. C Multinodular mass in the tarsal conjunctiva. D Aggressive recurrences can be non-pigmented.
Conjunctival melanoma. Invasive tumour with an epithelioid cell type.

Q: Clinically, Desmoplastic Melanoma often presents on sun-exposed skin of older adults as an indurated, firm plaque or nodule that lacks typical visual pigment, a presentation described as [...].
Desmoplastic melanoma. The range of appearances is broad; some examples arise in a pigmented patch; others, like this example, are amelanotic, level with the surface or elevated (as shown here), and (often) indurated.
A: amelanotic
Back Extra: Desmoplastic Melanoma
- Clinical: Desmoplastic melanoma often presents as a painless, indurated plaque on sun-exposed skin, predominantly in patients over 65 years old.
- Micro: The tumor is characterized by spindle-shaped melanocytes in a desmoplastic or fibrous stroma, with haphazardly distributed cells and an accompanying lymphocytic infiltrate.
- Ancillary: Immunohistochemically, the spindle cells are positive for S100, SOX10, and p75-NGFR, but usually negative for HMB45 and melan-A.
Reference Gallery:
Desmoplastic melanoma. The range of appearances is broad; some examples arise in a pigmented patch; others, like this example, are amelanotic, level with the surface or elevated (as shown here), and (often) indurated.
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. Thick neuroid bundles are present in the upper dermis; there are also occasional atypical junctional melanocytes, a few subepidermal spindle cells, and scattered lymphocytes.
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. A neuroid bundle (top) contains atypical elongated spindle nuclei; intraneural and perineural involvement of a small nerve is also present. There is a prominent infiltrate of lymphocytes.
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. Atypical spindle cells, some with elongated nuclei, are admixed with lymphocytes.
Desmoplastic melanoma in the cheek of a 73-year-old man. The increased cellularity in the dermis is due mainly to spindled melanocytes and lymphocytes; there is also patchy solar elastosis, deep acute haemorrhage, and epidermal thickening.
Desmoplastic melanoma in the cheek of a 73-year-old man. A few atypical enlarged melanocytes are present in the junctional zone. The fibrohistiocytic pattern is accompanied by scattered lymphocytes, some in clusters; mitoses are rare.
Desmoplastic melanoma in the cheek of a 73-year-old man. Atypical spindle cells with elongated nuclei appear to be within and between collagen bundles.
Desmoplastic melanoma in the forearm of a 76-year-old woman. Abnormal junctional melanocytes and dermal spindle cells with patchy lymphocytes.
Desmoplastic melanoma in the scalp of a 68-year-old man. This punch biopsy specimen was originally diagnosed as a scar; only an occasional spindle cell was S100-positive, and no abnormal junctional melanocytes were found. A larger desmoplastic melanoma was removed from the same site 6 months later; clues to the diagnosis are the small foci of lymphocytes and the haphazard permeation of the dermal zone of elastosis by spindle cells.
Desmoplastic melanoma. Scattered atypical spindle cells in dermis show nuclear expression of SOX10 with red chromogen.

Q: A biopsy of sun-damaged skin showing haphazardly distributed spindled melanocytes in a dense, fibrotic stroma with a patchy lymphocytic infiltrate and perineural invasion is highly characteristic of [...].
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. A neuroid bundle (top) contains atypical elongated spindle nuclei; intraneural and perineural involvement of a small nerve is also present. There is a prominent infiltrate of lymphocytes.
Desmoplastic melanoma in the scalp of a 68-year-old man. This punch biopsy specimen was originally diagnosed as a scar; only an occasional spindle cell was S100-positive, and no abnormal junctional melanocytes were found. A larger desmoplastic melanoma was removed from the same site 6 months later; clues to the diagnosis are the small foci of lymphocytes and the haphazard permeation of the dermal zone of elastosis by spindle cells.
A: Desmoplastic Melanoma
Back Extra: Desmoplastic Melanoma
- Clinical: Desmoplastic melanoma often presents as a painless, indurated plaque on sun-exposed skin, predominantly in patients over 65 years old.
- Micro: The tumor is characterized by spindle-shaped melanocytes in a desmoplastic or fibrous stroma, with haphazardly distributed cells and an accompanying lymphocytic infiltrate.
- Ancillary: Immunohistochemically, the spindle cells are positive for S100, SOX10, and p75-NGFR, but usually negative for HMB45 and melan-A.
Reference Gallery:
Desmoplastic melanoma. The range of appearances is broad; some examples arise in a pigmented patch; others, like this example, are amelanotic, level with the surface or elevated (as shown here), and (often) indurated.
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. Thick neuroid bundles are present in the upper dermis; there are also occasional atypical junctional melanocytes, a few subepidermal spindle cells, and scattered lymphocytes.
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. A neuroid bundle (top) contains atypical elongated spindle nuclei; intraneural and perineural involvement of a small nerve is also present. There is a prominent infiltrate of lymphocytes.
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. Atypical spindle cells, some with elongated nuclei, are admixed with lymphocytes.
Desmoplastic melanoma in the cheek of a 73-year-old man. The increased cellularity in the dermis is due mainly to spindled melanocytes and lymphocytes; there is also patchy solar elastosis, deep acute haemorrhage, and epidermal thickening.
Desmoplastic melanoma in the cheek of a 73-year-old man. A few atypical enlarged melanocytes are present in the junctional zone. The fibrohistiocytic pattern is accompanied by scattered lymphocytes, some in clusters; mitoses are rare.
Desmoplastic melanoma in the cheek of a 73-year-old man. Atypical spindle cells with elongated nuclei appear to be within and between collagen bundles.
Desmoplastic melanoma in the forearm of a 76-year-old woman. Abnormal junctional melanocytes and dermal spindle cells with patchy lymphocytes.
Desmoplastic melanoma in the scalp of a 68-year-old man. This punch biopsy specimen was originally diagnosed as a scar; only an occasional spindle cell was S100-positive, and no abnormal junctional melanocytes were found. A larger desmoplastic melanoma was removed from the same site 6 months later; clues to the diagnosis are the small foci of lymphocytes and the haphazard permeation of the dermal zone of elastosis by spindle cells.
Desmoplastic melanoma. Scattered atypical spindle cells in dermis show nuclear expression of SOX10 with red chromogen.

Q: Immunohistochemically, the atypical spindle cells of Desmoplastic Melanoma are typically negative for HMB45 and Melan-A, but retain strong positivity for S100 and nuclear [...].
Desmoplastic melanoma. Scattered atypical spindle cells in dermis show nuclear expression of SOX10 with red chromogen.
A: SOX10
Back Extra: Desmoplastic Melanoma
- Clinical: Desmoplastic melanoma often presents as a painless, indurated plaque on sun-exposed skin, predominantly in patients over 65 years old.
- Micro: The tumor is characterized by spindle-shaped melanocytes in a desmoplastic or fibrous stroma, with haphazardly distributed cells and an accompanying lymphocytic infiltrate.
- Ancillary: Immunohistochemically, the spindle cells are positive for S100, SOX10, and p75-NGFR, but usually negative for HMB45 and melan-A.
Reference Gallery:
Desmoplastic melanoma. The range of appearances is broad; some examples arise in a pigmented patch; others, like this example, are amelanotic, level with the surface or elevated (as shown here), and (often) indurated.
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. Thick neuroid bundles are present in the upper dermis; there are also occasional atypical junctional melanocytes, a few subepidermal spindle cells, and scattered lymphocytes.
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. A neuroid bundle (top) contains atypical elongated spindle nuclei; intraneural and perineural involvement of a small nerve is also present. There is a prominent infiltrate of lymphocytes.
Desmoplastic melanoma with so-called neural transforming areas in the lip of a 24-year-old woman. Atypical spindle cells, some with elongated nuclei, are admixed with lymphocytes.
Desmoplastic melanoma in the cheek of a 73-year-old man. The increased cellularity in the dermis is due mainly to spindled melanocytes and lymphocytes; there is also patchy solar elastosis, deep acute haemorrhage, and epidermal thickening.
Desmoplastic melanoma in the cheek of a 73-year-old man. A few atypical enlarged melanocytes are present in the junctional zone. The fibrohistiocytic pattern is accompanied by scattered lymphocytes, some in clusters; mitoses are rare.
Desmoplastic melanoma in the cheek of a 73-year-old man. Atypical spindle cells with elongated nuclei appear to be within and between collagen bundles.
Desmoplastic melanoma in the forearm of a 76-year-old woman. Abnormal junctional melanocytes and dermal spindle cells with patchy lymphocytes.
Desmoplastic melanoma in the scalp of a 68-year-old man. This punch biopsy specimen was originally diagnosed as a scar; only an occasional spindle cell was S100-positive, and no abnormal junctional melanocytes were found. A larger desmoplastic melanoma was removed from the same site 6 months later; clues to the diagnosis are the small foci of lymphocytes and the haphazard permeation of the dermal zone of elastosis by spindle cells.
Desmoplastic melanoma. Scattered atypical spindle cells in dermis show nuclear expression of SOX10 with red chromogen.

Q: The most common genetic cause of Familial Melanoma is a germline mutation in the [...] gene.
Familial melanoma pathways. Schematic illustration of pathways important in familial melanoma (see text).
A: CDKN2A
Back Extra: Familial Melanoma
- Clinical: Familial melanomas often present with multiple primary melanomas and a high frequency of atypical nevi, with a strong association with germline CDKN2A variants.
- Micro: Histopathological features include superficial spreading melanoma with increased pigmentation and pagetoid scatter, similar to sporadic melanomas.
- Ancillary: p16 (p16INK4a) immunohistochemistry can be used to detect CDK4 activation, which is a risk factor for familial melanoma.
Reference Gallery:
Familial melanoma pathways. Schematic illustration of pathways important in familial melanoma (see text).

Q: In Uveal Melanoma, the [...] cell type (characterized by distinct cytoplasmic margins, large nuclei, and prominent nucleoli) is associated with the worst prognosis compared to spindle cell variants.
Choroidal melanoma. Spindle cell type; spindle B cells have prominent nucleoli and form a syncytium.
Choroidal melanoma. Epithelioid cell type; epithelioid cells have distinct cytoplasmic margins and large round or oval nuclei with prominent reddish-purple nucleoli and peripheral margination of chromatin.
Choroidal melanoma. Mixed cell type; this mixed cell melanoma comprises clones of pigmented spindle cells (bottom left) and amelanotic epithelioid cells (top right).
A: epithelioid
Back Extra: Uveal Melanoma
- Clinical: Uveal melanomas can present with symptoms such as photopsia, floaters, and loss of vision, or they may be asymptomatic and detected during routine eye examinations.
- Micro: Uveal melanomas can be classified into spindle A, spindle B, epithelioid, and mixed cell types, with epithelioid cell type being associated with the worst prognosis.
- Ancillary: BAP1 immunostaining is a crucial ancillary test, where lack of nuclear immunostaining indicates a high risk of metastasis.
Reference Gallery:
Ciliary body melanoma. A tumour invading the anterior chamber. Gonioscopic examination shows a pigmented melanoma invading the anterior chamber angle: a band of tumour also blankets the adjacent trabecular meshwork.
Choroidal melanoma. A variably pigmented choroidal melanoma is heavily pigmented in one area (asterisk) and amelanotic in another (arrow).
Choroidal melanoma. An amelanotic choroidal melanoma has broken through the Bruch membrane and thus assumed a mushroom (collar button) shape. Congested vascular channels are visible in the portion of the tumour internal to the Bruch membrane, and a serous retinal detachment is present around the tumour.
Ciliochoroidal melanoma. An exenteration specimen contains a heavily pigmented choroidal melanoma that fills the eye (UM), invades the optic nerve (arrow), and extends beyond the sclera into the orbit where it forms a large nodule (asterisk).
Choroidal melanoma. Spindle cell type; spindle B cells have prominent nucleoli and form a syncytium.
Choroidal melanoma. Epithelioid cell type; epithelioid cells have distinct cytoplasmic margins and large round or oval nuclei with prominent reddish-purple nucleoli and peripheral margination of chromatin.
Choroidal melanoma. Mixed cell type; this mixed cell melanoma comprises clones of pigmented spindle cells (bottom left) and amelanotic epithelioid cells (top right).
Choroidal melanoma. Necrosis of melanoma tissue may occur spontaneously, and it can be difficult to diagnose (particularly in cases without substantial pigmentation).
Choroidal melanoma. BAP1-positive. Immunohistochemistry for BAP1 labels the nuclei.

Q: A crucial ancillary test in the workup of Uveal Melanoma is immunohistochemistry for [...], where a lack of nuclear staining indicates a high risk of metastasis.
Choroidal melanoma. BAP1-positive. Immunohistochemistry for BAP1 labels the nuclei.
A: BAP1
Back Extra: Uveal Melanoma
- Clinical: Uveal melanomas can present with symptoms such as photopsia, floaters, and loss of vision, or they may be asymptomatic and detected during routine eye examinations.
- Micro: Uveal melanomas can be classified into spindle A, spindle B, epithelioid, and mixed cell types, with epithelioid cell type being associated with the worst prognosis.
- Ancillary: BAP1 immunostaining is a crucial ancillary test, where lack of nuclear immunostaining indicates a high risk of metastasis.
Reference Gallery:
Ciliary body melanoma. A tumour invading the anterior chamber. Gonioscopic examination shows a pigmented melanoma invading the anterior chamber angle: a band of tumour also blankets the adjacent trabecular meshwork.
Choroidal melanoma. A variably pigmented choroidal melanoma is heavily pigmented in one area (asterisk) and amelanotic in another (arrow).
Choroidal melanoma. An amelanotic choroidal melanoma has broken through the Bruch membrane and thus assumed a mushroom (collar button) shape. Congested vascular channels are visible in the portion of the tumour internal to the Bruch membrane, and a serous retinal detachment is present around the tumour.
Ciliochoroidal melanoma. An exenteration specimen contains a heavily pigmented choroidal melanoma that fills the eye (UM), invades the optic nerve (arrow), and extends beyond the sclera into the orbit where it forms a large nodule (asterisk).
Choroidal melanoma. Spindle cell type; spindle B cells have prominent nucleoli and form a syncytium.
Choroidal melanoma. Epithelioid cell type; epithelioid cells have distinct cytoplasmic margins and large round or oval nuclei with prominent reddish-purple nucleoli and peripheral margination of chromatin.
Choroidal melanoma. Mixed cell type; this mixed cell melanoma comprises clones of pigmented spindle cells (bottom left) and amelanotic epithelioid cells (top right).
Choroidal melanoma. Necrosis of melanoma tissue may occur spontaneously, and it can be difficult to diagnose (particularly in cases without substantial pigmentation).
Choroidal melanoma. BAP1-positive. Immunohistochemistry for BAP1 labels the nuclei.

Q: The classic microscopic pattern of [...] features a continuous, poorly circumscribed lentiginous proliferation of atypical melanocytes with epidermal thinning, loss of rete ridges, and underlying severe solar elastosis.
Lentigo maligna. This field shows the so-called classic pattern, with continuous basal (lentiginous) proliferation of uniformly atypical naevoid to epithelioid melanocytes.
Lentigo maligna melanoma, invasive. Predominantly basal proliferation of moderately and uniformly atypical naevoid to epithelioid and spindle melanocytes; there is focal low-level suprabasal scatter and there are a few nests that appear to hang down from the epidermis in a droplet-like pattern; the process is in situ in this field.
A: High-CSD Melanoma (including Lentigo Maligna Melanoma)
Back Extra: High-CSD Melanoma (including Lentigo Maligna Melanoma)
- Clinical: Lentigo maligna presents as an expanding asymmetrical patch with irregular indistinct borders and varying color. Amelanotic lesions present as an erythematous patch.
- Micro: High-CSD melanoma and LMM are poorly circumscribed lentiginous proliferations of atypical melanocytes with epidermal thinning and loss of rete ridges, often on skin with severe solar elastosis.
- Ancillary: Melan-A and SOX10 can be useful in assessing the cellularity and degree of confluence of the junctional melanocytic proliferation and reveal occult invasion.
Reference Gallery:
Lentigo maligna melanoma. Lentigo maligna melanoma characteristically has a prolonged radial growth phase, exemplified by this lesion, which was present for more than 15 years without a vertical growth phase.
Lentigo maligna. This field shows the so-called classic pattern, with continuous basal (lentiginous) proliferation of uniformly atypical naevoid to epithelioid melanocytes.
Lentigo maligna. Another field shows the dysplastic naevus–like (or naevoid lentigo maligna) pattern, although this single field is not diagnostic of lentigo maligna.
Lentigo maligna melanoma, invasive. Predominantly basal proliferation of moderately and uniformly atypical naevoid to epithelioid and spindle melanocytes; there is focal low-level suprabasal scatter and there are a few nests that appear to hang down from the epidermis in a droplet-like pattern; the process is in situ in this field.
Lentigo maligna melanoma, invasive. There is a collection of cells in the papillary dermis, filling and expanding it. The cells have a somewhat naevoid morphology (relatively small, scant cytoplasm), and there is evidence suggesting maturation to a smaller cell type at the base, but the nuclei are hyperchromatic and irregular. There are no mitoses; the invasive component in lentigo maligna melanoma is often somewhat naevoid, as in this case; the tumour thickness is 0.3 mm, indicative of a lesion at minimal risk of metastasis.
Lentigo maligna melanoma. Clinical features of a lentigo maligna melanoma.
Lentigo maligna melanoma. Dermoscopic features. Minimally invasive lentigo maligna melanoma on the ala of the nose of a 90-year-old patient. Dermoscopy reveals grey-brown rhomboidal lines, asymmetrically pigmented circles, and grey dots.
Lentigo maligna melanoma. Dermoscopic features. Invasive lentigo maligna melanoma on the ala of the nose of a man in his sixties. Note that the lesion represents a solitary spot on otherwise healthy-appearing skin. Dermoscopy reveals grey thickened lines around the hair follicles, grey dots, and diffuse ill-marked brownish pigmentation.
Lentigo maligna and primary acquired melanosis of the conjunctiva. Lentigo maligna / lentigo maligna melanoma involving the face, eyelid, and conjunctiva.

Q: Dermoscopy of early facial lesions in [...] characteristically reveals gray-brown rhomboidal lines, asymmetrically pigmented circles, and gray dots within an asymmetrical patch on chronically sun-damaged skin.
Lentigo maligna melanoma. Dermoscopic features. Minimally invasive lentigo maligna melanoma on the ala of the nose of a 90-year-old patient. Dermoscopy reveals grey-brown rhomboidal lines, asymmetrically pigmented circles, and grey dots.
Lentigo maligna melanoma. Dermoscopic features. Invasive lentigo maligna melanoma on the ala of the nose of a man in his sixties. Note that the lesion represents a solitary spot on otherwise healthy-appearing skin. Dermoscopy reveals grey thickened lines around the hair follicles, grey dots, and diffuse ill-marked brownish pigmentation.
A: High-CSD Melanoma (including Lentigo Maligna Melanoma)
Back Extra: High-CSD Melanoma (including Lentigo Maligna Melanoma)
- Clinical: Lentigo maligna presents as an expanding asymmetrical patch with irregular indistinct borders and varying color. Amelanotic lesions present as an erythematous patch.
- Micro: High-CSD melanoma and LMM are poorly circumscribed lentiginous proliferations of atypical melanocytes with epidermal thinning and loss of rete ridges, often on skin with severe solar elastosis.
- Ancillary: Melan-A and SOX10 can be useful in assessing the cellularity and degree of confluence of the junctional melanocytic proliferation and reveal occult invasion.
Reference Gallery:
Lentigo maligna melanoma. Lentigo maligna melanoma characteristically has a prolonged radial growth phase, exemplified by this lesion, which was present for more than 15 years without a vertical growth phase.
Lentigo maligna. This field shows the so-called classic pattern, with continuous basal (lentiginous) proliferation of uniformly atypical naevoid to epithelioid melanocytes.
Lentigo maligna. Another field shows the dysplastic naevus–like (or naevoid lentigo maligna) pattern, although this single field is not diagnostic of lentigo maligna.
Lentigo maligna melanoma, invasive. Predominantly basal proliferation of moderately and uniformly atypical naevoid to epithelioid and spindle melanocytes; there is focal low-level suprabasal scatter and there are a few nests that appear to hang down from the epidermis in a droplet-like pattern; the process is in situ in this field.
Lentigo maligna melanoma, invasive. There is a collection of cells in the papillary dermis, filling and expanding it. The cells have a somewhat naevoid morphology (relatively small, scant cytoplasm), and there is evidence suggesting maturation to a smaller cell type at the base, but the nuclei are hyperchromatic and irregular. There are no mitoses; the invasive component in lentigo maligna melanoma is often somewhat naevoid, as in this case; the tumour thickness is 0.3 mm, indicative of a lesion at minimal risk of metastasis.
Lentigo maligna melanoma. Clinical features of a lentigo maligna melanoma.
Lentigo maligna melanoma. Dermoscopic features. Minimally invasive lentigo maligna melanoma on the ala of the nose of a 90-year-old patient. Dermoscopy reveals grey-brown rhomboidal lines, asymmetrically pigmented circles, and grey dots.
Lentigo maligna melanoma. Dermoscopic features. Invasive lentigo maligna melanoma on the ala of the nose of a man in his sixties. Note that the lesion represents a solitary spot on otherwise healthy-appearing skin. Dermoscopy reveals grey thickened lines around the hair follicles, grey dots, and diffuse ill-marked brownish pigmentation.
Lentigo maligna and primary acquired melanosis of the conjunctiva. Lentigo maligna / lentigo maligna melanoma involving the face, eyelid, and conjunctiva.

Q: When High-CSD Melanoma (including Lentigo Maligna Melanoma) becomes invasive, the tumor cells expanding the papillary dermis frequently exhibit a deceptively [...] morphology, characterized by relatively small cells with scant cytoplasm that mimic benign maturation.
Lentigo maligna melanoma, invasive. There is a collection of cells in the papillary dermis, filling and expanding it. The cells have a somewhat naevoid morphology (relatively small, scant cytoplasm), and there is evidence suggesting maturation to a smaller cell type at the base, but the nuclei are hyperchromatic and irregular. There are no mitoses; the invasive component in lentigo maligna melanoma is often somewhat naevoid, as in this case; the tumour thickness is 0.3 mm, indicative of a lesion at minimal risk of metastasis.
A: nevoid
Back Extra: High-CSD Melanoma (including Lentigo Maligna Melanoma)
- Clinical: Lentigo maligna presents as an expanding asymmetrical patch with irregular indistinct borders and varying color. Amelanotic lesions present as an erythematous patch.
- Micro: High-CSD melanoma and LMM are poorly circumscribed lentiginous proliferations of atypical melanocytes with epidermal thinning and loss of rete ridges, often on skin with severe solar elastosis.
- Ancillary: Melan-A and SOX10 can be useful in assessing the cellularity and degree of confluence of the junctional melanocytic proliferation and reveal occult invasion.
Reference Gallery:
Lentigo maligna melanoma. Lentigo maligna melanoma characteristically has a prolonged radial growth phase, exemplified by this lesion, which was present for more than 15 years without a vertical growth phase.
Lentigo maligna. This field shows the so-called classic pattern, with continuous basal (lentiginous) proliferation of uniformly atypical naevoid to epithelioid melanocytes.
Lentigo maligna. Another field shows the dysplastic naevus–like (or naevoid lentigo maligna) pattern, although this single field is not diagnostic of lentigo maligna.
Lentigo maligna melanoma, invasive. Predominantly basal proliferation of moderately and uniformly atypical naevoid to epithelioid and spindle melanocytes; there is focal low-level suprabasal scatter and there are a few nests that appear to hang down from the epidermis in a droplet-like pattern; the process is in situ in this field.
Lentigo maligna melanoma, invasive. There is a collection of cells in the papillary dermis, filling and expanding it. The cells have a somewhat naevoid morphology (relatively small, scant cytoplasm), and there is evidence suggesting maturation to a smaller cell type at the base, but the nuclei are hyperchromatic and irregular. There are no mitoses; the invasive component in lentigo maligna melanoma is often somewhat naevoid, as in this case; the tumour thickness is 0.3 mm, indicative of a lesion at minimal risk of metastasis.
Lentigo maligna melanoma. Clinical features of a lentigo maligna melanoma.
Lentigo maligna melanoma. Dermoscopic features. Minimally invasive lentigo maligna melanoma on the ala of the nose of a 90-year-old patient. Dermoscopy reveals grey-brown rhomboidal lines, asymmetrically pigmented circles, and grey dots.
Lentigo maligna melanoma. Dermoscopic features. Invasive lentigo maligna melanoma on the ala of the nose of a man in his sixties. Note that the lesion represents a solitary spot on otherwise healthy-appearing skin. Dermoscopy reveals grey thickened lines around the hair follicles, grey dots, and diffuse ill-marked brownish pigmentation.
Lentigo maligna and primary acquired melanosis of the conjunctiva. Lentigo maligna / lentigo maligna melanoma involving the face, eyelid, and conjunctiva.

Q: In melanoma metastatic to other organs, tumor cells can exhibit an angiotropic infiltration pattern, arrayed along the abluminal surfaces of vascular channels in a [...] location without intravascular involvement.
Cutaneous melanoma metastasis, liver. Metastasis (Met) in lower third of field, with replacement histopathological growth pattern. The interface between the metastasis and liver parenchyma (Liv) above is poorly defined. Melanoma cells are dispersed as single cells and in small clusters (arrows) throughout the liver parenchyma considerable distances from the metastasis. These cells replace hepatocytes and are arranged along the external surfaces of sinusoidal microvascular channels in the hepatic plates without altering their architecture. Inset: HMB45 immunostain with red chromogen highlights melanoma cells in the liver parenchyma along the abluminal endothelial surfaces of sinusoidal vessels.
Melanoma metastasis, brain. Pigmented epithelioid melanoma cells exhibit diffuse angiotropic infiltration of the brain parenchyma. Tumour cells are arrayed along the abluminal (external) surfaces of vascular channels in a pericytic location. Intravascular (luminal) involvement is not observed.
A: pericytic
Melanoma Metastatic to Other Organs
- Clinical: The most common presentation of melanoma metastatic to other organs is regional lymph node spread with sentinel or palpable clinical nodal involvement in patients with prior primary cutaneous melanoma.
- Micro: In melanoma metastatic to other organs, tumour cells can infiltrate and replace surrounding tissue in a non-disruptive pattern, often along vascular channels in a pericytic location.
- Ancillary: Immunohistochemistry, particularly with markers like HMB45, SOX10, and Melan-A, is crucial for confirming the diagnosis of melanoma metastatic to other organs.
Reference Gallery:
Cutaneous melanoma metastasis, liver. Metastasis (Met) in lower third of field, with replacement histopathological growth pattern. The interface between the metastasis and liver parenchyma (Liv) above is poorly defined. Melanoma cells are dispersed as single cells and in small clusters (arrows) throughout the liver parenchyma considerable distances from the metastasis. These cells replace hepatocytes and are arranged along the external surfaces of sinusoidal microvascular channels in the hepatic plates without altering their architecture. Inset: HMB45 immunostain with red chromogen highlights melanoma cells in the liver parenchyma along the abluminal endothelial surfaces of sinusoidal vessels.
Uveal melanoma metastasis, liver. The desmoplastic histopathological growth pattern as shown here is characterized by a well-defined annulus of desmoplasia separating the metastasis from the surrounding liver parenchyma.
Melanoma metastasis, brain. Nodule of metastatic melanoma in the brain composed of pigmented epithelioid melanoma cells.
Melanoma metastasis, brain. Pigmented epithelioid melanoma cells exhibit diffuse angiotropic infiltration of the brain parenchyma. Tumour cells are arrayed along the abluminal (external) surfaces of vascular channels in a pericytic location. Intravascular (luminal) involvement is not observed.
Melanoma metastasis, sentinel lymph node. This field shows small cellular aggregates suspicious for melanoma at scanning magnification.
Melanoma metastasis, sentinel lymph node. Expansile mass of slightly pigmented melanoma cells.
Melanoma metastasis, sentinel lymph node. SOX10 immunostain is positive in melanoma cells (red chromogen).
Melanoma metastasis, lymph node. Expansile aggregates of heavily pigmented melanoma cells are seen at scanning magnification.
Melanoma metastasis, lymph node. Heavily pigmented epithelioid melanoma cells are observed.

Q: The diagnosis of [...] is often confirmed using immunohistochemistry for specific melanocytic markers such as HMB45, SOX10, and Melan-A.
Cutaneous melanoma metastasis, liver. Metastasis (Met) in lower third of field, with replacement histopathological growth pattern. The interface between the metastasis and liver parenchyma (Liv) above is poorly defined. Melanoma cells are dispersed as single cells and in small clusters (arrows) throughout the liver parenchyma considerable distances from the metastasis. These cells replace hepatocytes and are arranged along the external surfaces of sinusoidal microvascular channels in the hepatic plates without altering their architecture. Inset: HMB45 immunostain with red chromogen highlights melanoma cells in the liver parenchyma along the abluminal endothelial surfaces of sinusoidal vessels.
Melanoma metastasis, sentinel lymph node. SOX10 immunostain is positive in melanoma cells (red chromogen).
A: melanoma metastatic to other organs
Melanoma Metastatic to Other Organs
- Clinical: The most common presentation of melanoma metastatic to other organs is regional lymph node spread with sentinel or palpable clinical nodal involvement in patients with prior primary cutaneous melanoma.
- Micro: In melanoma metastatic to other organs, tumour cells can infiltrate and replace surrounding tissue in a non-disruptive pattern, often along vascular channels in a pericytic location.
- Ancillary: Immunohistochemistry, particularly with markers like HMB45, SOX10, and Melan-A, is crucial for confirming the diagnosis of melanoma metastatic to other organs.
Reference Gallery:
Cutaneous melanoma metastasis, liver. Metastasis (Met) in lower third of field, with replacement histopathological growth pattern. The interface between the metastasis and liver parenchyma (Liv) above is poorly defined. Melanoma cells are dispersed as single cells and in small clusters (arrows) throughout the liver parenchyma considerable distances from the metastasis. These cells replace hepatocytes and are arranged along the external surfaces of sinusoidal microvascular channels in the hepatic plates without altering their architecture. Inset: HMB45 immunostain with red chromogen highlights melanoma cells in the liver parenchyma along the abluminal endothelial surfaces of sinusoidal vessels.
Uveal melanoma metastasis, liver. The desmoplastic histopathological growth pattern as shown here is characterized by a well-defined annulus of desmoplasia separating the metastasis from the surrounding liver parenchyma.
Melanoma metastasis, brain. Nodule of metastatic melanoma in the brain composed of pigmented epithelioid melanoma cells.
Melanoma metastasis, brain. Pigmented epithelioid melanoma cells exhibit diffuse angiotropic infiltration of the brain parenchyma. Tumour cells are arrayed along the abluminal (external) surfaces of vascular channels in a pericytic location. Intravascular (luminal) involvement is not observed.
Melanoma metastasis, sentinel lymph node. This field shows small cellular aggregates suspicious for melanoma at scanning magnification.
Melanoma metastasis, sentinel lymph node. Expansile mass of slightly pigmented melanoma cells.
Melanoma metastasis, sentinel lymph node. SOX10 immunostain is positive in melanoma cells (red chromogen).
Melanoma metastasis, lymph node. Expansile aggregates of heavily pigmented melanoma cells are seen at scanning magnification.
Melanoma metastasis, lymph node. Heavily pigmented epithelioid melanoma cells are observed.

Q: The most common presentation of [...] is regional lymph node spread, frequently identified as heavily pigmented epithelioid tumor cells in sentinel or palpable clinical nodal biopsies.
Melanoma metastasis, sentinel lymph node. This field shows small cellular aggregates suspicious for melanoma at scanning magnification.
Melanoma metastasis, sentinel lymph node. Expansile mass of slightly pigmented melanoma cells.
Melanoma metastasis, lymph node. Heavily pigmented epithelioid melanoma cells are observed.
A: melanoma metastatic to other organs
Melanoma Metastatic to Other Organs
- Clinical: The most common presentation of melanoma metastatic to other organs is regional lymph node spread with sentinel or palpable clinical nodal involvement in patients with prior primary cutaneous melanoma.
- Micro: In melanoma metastatic to other organs, tumour cells can infiltrate and replace surrounding tissue in a non-disruptive pattern, often along vascular channels in a pericytic location.
- Ancillary: Immunohistochemistry, particularly with markers like HMB45, SOX10, and Melan-A, is crucial for confirming the diagnosis of melanoma metastatic to other organs.
Reference Gallery:
Cutaneous melanoma metastasis, liver. Metastasis (Met) in lower third of field, with replacement histopathological growth pattern. The interface between the metastasis and liver parenchyma (Liv) above is poorly defined. Melanoma cells are dispersed as single cells and in small clusters (arrows) throughout the liver parenchyma considerable distances from the metastasis. These cells replace hepatocytes and are arranged along the external surfaces of sinusoidal microvascular channels in the hepatic plates without altering their architecture. Inset: HMB45 immunostain with red chromogen highlights melanoma cells in the liver parenchyma along the abluminal endothelial surfaces of sinusoidal vessels.
Uveal melanoma metastasis, liver. The desmoplastic histopathological growth pattern as shown here is characterized by a well-defined annulus of desmoplasia separating the metastasis from the surrounding liver parenchyma.
Melanoma metastasis, brain. Nodule of metastatic melanoma in the brain composed of pigmented epithelioid melanoma cells.
Melanoma metastasis, brain. Pigmented epithelioid melanoma cells exhibit diffuse angiotropic infiltration of the brain parenchyma. Tumour cells are arrayed along the abluminal (external) surfaces of vascular channels in a pericytic location. Intravascular (luminal) involvement is not observed.
Melanoma metastasis, sentinel lymph node. This field shows small cellular aggregates suspicious for melanoma at scanning magnification.
Melanoma metastasis, sentinel lymph node. Expansile mass of slightly pigmented melanoma cells.
Melanoma metastasis, sentinel lymph node. SOX10 immunostain is positive in melanoma cells (red chromogen).
Melanoma metastasis, lymph node. Expansile aggregates of heavily pigmented melanoma cells are seen at scanning magnification.
Melanoma metastasis, lymph node. Heavily pigmented epithelioid melanoma cells are observed.

Q: A clinical presentation of multiple new pigmented, elevated lesions on the skin (often in a zosteriform or erysipelas-like formation) in a patient with a prior history of melanoma is classic for [...].
Metastatic melanoma. Multiple new lesions on the leg of a patient with a previous history of melanoma. Lesions are pigmented, some of them elevated.
A: Metastatic Melanoma to the Skin
Back Extra: Metastatic Melanoma to the Skin
- Clinical: Metastatic melanoma to the skin often presents as one or several pigmented or amelanotic nodules or plaques, sometimes in a zosteriform or erysipelas-like formation.
- Micro: Histologically, metastatic melanoma in the skin shows a well-circumscribed nodule in the dermis and/or subcutis, with sheets of atypical melanocytes and mitoses.
- Ancillary: Neoplastic melanocytes in metastatic melanoma express melanocytic markers such as melan-A, SOX10, HMB45, and S100.
Reference Gallery:
Metastatic melanoma. Solitary, well-circumscribed nodule of metastatic melanoma in the subcutis.
Melanoma metastatic to the skin, angiotropism of melanoma cells. Melanoma cells are disposed about the abluminal surface of a dermal microvascular channel (arrow), without intravasation. This pattern of spread can be seen in microscopic satellites and in transit and distant metastases.
Metastatic melanoma. Multiple new lesions on the leg of a patient with a previous history of melanoma. Lesions are pigmented, some of them elevated.

Q: Histologically, a solitary, well-circumscribed nodule in the deep dermis or subcutis composed of sheets of atypical melanocytes with frequent mitoses is a classic architectural pattern for [...].
Metastatic melanoma. Solitary, well-circumscribed nodule of metastatic melanoma in the subcutis.
A: Metastatic Melanoma to the Skin
Back Extra: Metastatic Melanoma to the Skin
- Clinical: Metastatic melanoma to the skin often presents as one or several pigmented or amelanotic nodules or plaques, sometimes in a zosteriform or erysipelas-like formation.
- Micro: Histologically, metastatic melanoma in the skin shows a well-circumscribed nodule in the dermis and/or subcutis, with sheets of atypical melanocytes and mitoses.
- Ancillary: Neoplastic melanocytes in metastatic melanoma express melanocytic markers such as melan-A, SOX10, HMB45, and S100.
Reference Gallery:
Metastatic melanoma. Solitary, well-circumscribed nodule of metastatic melanoma in the subcutis.
Melanoma metastatic to the skin, angiotropism of melanoma cells. Melanoma cells are disposed about the abluminal surface of a dermal microvascular channel (arrow), without intravasation. This pattern of spread can be seen in microscopic satellites and in transit and distant metastases.
Metastatic melanoma. Multiple new lesions on the leg of a patient with a previous history of melanoma. Lesions are pigmented, some of them elevated.

Q: In Metastatic Melanoma to the Skin, tumor cells may be disposed around the abluminal surface of dermal microvascular channels without true intravasation, a specific pattern of spread known as [...].
Melanoma metastatic to the skin, angiotropism of melanoma cells. Melanoma cells are disposed about the abluminal surface of a dermal microvascular channel (arrow), without intravasation. This pattern of spread can be seen in microscopic satellites and in transit and distant metastases.
A: angiotropism
Back Extra: Metastatic Melanoma to the Skin
- Clinical: Metastatic melanoma to the skin often presents as one or several pigmented or amelanotic nodules or plaques, sometimes in a zosteriform or erysipelas-like formation.
- Micro: Histologically, metastatic melanoma in the skin shows a well-circumscribed nodule in the dermis and/or subcutis, with sheets of atypical melanocytes and mitoses.
- Ancillary: Neoplastic melanocytes in metastatic melanoma express melanocytic markers such as melan-A, SOX10, HMB45, and S100.
Reference Gallery:
Metastatic melanoma. Solitary, well-circumscribed nodule of metastatic melanoma in the subcutis.
Melanoma metastatic to the skin, angiotropism of melanoma cells. Melanoma cells are disposed about the abluminal surface of a dermal microvascular channel (arrow), without intravasation. This pattern of spread can be seen in microscopic satellites and in transit and distant metastases.
Metastatic melanoma. Multiple new lesions on the leg of a patient with a previous history of melanoma. Lesions are pigmented, some of them elevated.

Q: In Mucosal Melanoma, the adjacent squamous epithelium frequently exhibits a [...] proliferation of atypical melanocytes, often accompanied by subepithelial melanophages and lymphocytes.
Mucosal melanoma. The invasive tumour is composed of uniformly atypical epithelioid cells (bottom left), admixed with numerous melanophages. There is involvement of the overlying epithelium by atypical melanocytes, mostly basal in this field.
Mucosal melanoma. In the squamous epithelium adjacent to a mucosal melanoma, there is a basal (lentiginous) proliferation of atypical melanocytes (relatively subtle, as is often the case), with melanophages and lymphocytes in the subepithelial stroma.
A: basal (lentiginous)
Back Extra: Mucosal Melanoma
- Clinical: Mucosal melanomas typically present as irregularly pigmented macules or plaques in older patients, often with nonspecific symptoms such as nasal obstruction, epistaxis, and sinus congestion.
- Micro: The invasive areas of mucosal melanoma are usually composed of sheets and expansive nodules of large pleomorphic and large epithelioid cells, with variable melanin production and a common subepithelial lymphocytic infiltrate.
- Ancillary: Immunohistochemistry for S100, SOX10, MITF, HMB45, and melan-A is usually positive, and characteristic somatic mutations such as BRAF, NRAS, and KIT are commonly identified.
Reference Gallery:
Mucosal melanoma. The invasive tumour is composed of uniformly atypical epithelioid cells (bottom left), admixed with numerous melanophages. There is involvement of the overlying epithelium by atypical melanocytes, mostly basal in this field.
Mucosal melanoma. In the squamous epithelium adjacent to a mucosal melanoma, there is a basal (lentiginous) proliferation of atypical melanocytes (relatively subtle, as is often the case), with melanophages and lymphocytes in the subepithelial stroma.
Mucosal melanoma. Melanomas of the oral cavity or the vulvovaginal or urethral mucosae can present as a bulky tumour, as seen in this microscopic field.
Mucosal melanoma. Lower part of the oral mucosa of a multifocal melanoma.
Mucosal melanoma. Vulvar tumour in a 65-year-old woman. Large atypical epithelioid melanocytes, with scattered melanophages and high mitotic activity, are seen in this lesion.

Q: An older woman presents with an irregularly pigmented, bulky vulvar tumor. Biopsy reveals an invasive proliferation of large, atypical epithelioid cells with high mitotic activity and scattered melanophages, diagnostic of [...].
Mucosal melanoma. Melanomas of the oral cavity or the vulvovaginal or urethral mucosae can present as a bulky tumour, as seen in this microscopic field.
Mucosal melanoma. Vulvar tumour in a 65-year-old woman. Large atypical epithelioid melanocytes, with scattered melanophages and high mitotic activity, are seen in this lesion.
A: Mucosal Melanoma
Back Extra: Mucosal Melanoma
- Clinical: Mucosal melanomas typically present as irregularly pigmented macules or plaques in older patients, often with nonspecific symptoms such as nasal obstruction, epistaxis, and sinus congestion.
- Micro: The invasive areas of mucosal melanoma are usually composed of sheets and expansive nodules of large pleomorphic and large epithelioid cells, with variable melanin production and a common subepithelial lymphocytic infiltrate.
- Ancillary: Immunohistochemistry for S100, SOX10, MITF, HMB45, and melan-A is usually positive, and characteristic somatic mutations such as BRAF, NRAS, and KIT are commonly identified.
Reference Gallery:
Mucosal melanoma. The invasive tumour is composed of uniformly atypical epithelioid cells (bottom left), admixed with numerous melanophages. There is involvement of the overlying epithelium by atypical melanocytes, mostly basal in this field.
Mucosal melanoma. In the squamous epithelium adjacent to a mucosal melanoma, there is a basal (lentiginous) proliferation of atypical melanocytes (relatively subtle, as is often the case), with melanophages and lymphocytes in the subepithelial stroma.
Mucosal melanoma. Melanomas of the oral cavity or the vulvovaginal or urethral mucosae can present as a bulky tumour, as seen in this microscopic field.
Mucosal melanoma. Lower part of the oral mucosa of a multifocal melanoma.
Mucosal melanoma. Vulvar tumour in a 65-year-old woman. Large atypical epithelioid melanocytes, with scattered melanophages and high mitotic activity, are seen in this lesion.

Q: A deceptively bland melanocytic neoplasm that mimics a benign intradermal nevus at low power, but features crowded atypical cells with enlarged nucleoli and deep dermal mitoses at high power, is characteristic of [...].
Naevoid melanoma. At low power, this lesion resembles a benign intradermal melanocytic naevus.
Naevoid melanoma. Haematoxylin eosin saffron stain. Papillomatous pattern. The melanocytes are atypical, with crowded, sometimes hyperchromatic nuclei and enlarged nucleoli. Mitoses are seen.
A: Naevoid Melanoma
Back Extra: Naevoid Melanoma
- Clinical: Naevoid melanomas can present as a papule or nodule with varying or no pigmentation, often resembling an intradermal or benign naevus.
- Micro: The neoplastic melanocytes in naevoid melanoma are small to intermediate in size, with less atypia and maturation with descent into the reticular dermis. Mitoses are a key diagnostic clue.
- Ancillary: Immunohistochemical staining for p16, Ki-67, and PRAME is helpful, and molecular studies often show mutations in BRAF or NRAS.
Reference Gallery:
Naevoid melanoma. At low power, this lesion resembles a benign intradermal melanocytic naevus.
Naevoid melanoma. Haematoxylin eosin saffron stain. Papillomatous pattern. “Puffy-shirt” silhouette lesion characterized by elongated thin rete ridges separating the melanocytic component into compartments.
Naevoid melanoma. Haematoxylin eosin saffron stain. Papillomatous pattern. The melanocytes are atypical, with crowded, sometimes hyperchromatic nuclei and enlarged nucleoli. Mitoses are seen.

Q: In the papillomatous variant of Naevoid Melanoma, elongated thin rete ridges separate the melanocytic component into distinct compartments, creating a characteristic [...] silhouette.
Naevoid melanoma. Haematoxylin eosin saffron stain. Papillomatous pattern. “Puffy-shirt” silhouette lesion characterized by elongated thin rete ridges separating the melanocytic component into compartments.
A: "puffy-shirt"
Back Extra: Naevoid Melanoma
- Clinical: Naevoid melanomas can present as a papule or nodule with varying or no pigmentation, often resembling an intradermal or benign naevus.
- Micro: The neoplastic melanocytes in naevoid melanoma are small to intermediate in size, with less atypia and maturation with descent into the reticular dermis. Mitoses are a key diagnostic clue.
- Ancillary: Immunohistochemical staining for p16, Ki-67, and PRAME is helpful, and molecular studies often show mutations in BRAF or NRAS.
Reference Gallery:
Naevoid melanoma. At low power, this lesion resembles a benign intradermal melanocytic naevus.
Naevoid melanoma. Haematoxylin eosin saffron stain. Papillomatous pattern. “Puffy-shirt” silhouette lesion characterized by elongated thin rete ridges separating the melanocytic component into compartments.
Naevoid melanoma. Haematoxylin eosin saffron stain. Papillomatous pattern. The melanocytes are atypical, with crowded, sometimes hyperchromatic nuclei and enlarged nucleoli. Mitoses are seen.

Q: Clinically, Nodular Melanoma typically presents as rapidly growing, pigmented or unpigmented nodules that frequently [...] and bleed.
Nodular melanoma. Lesion located on the trunk, with positive sentinel lymph node. A symmetrical pigmented nodule, bluish-reddish, with regular borders is observed.
A: ulcerate
Back Extra: Nodular Melanoma
- Clinical: Nodular melanomas often present as rapidly growing, pigmented or unpigmented nodules that can ulcerate and bleed.
- Micro: Characterized by cohesive aggregates of epithelioid or spindled neoplastic melanocytes in the dermis, with an inflammatory infiltrate and fibrosing stromal reaction.
- Ancillary: Immunohistochemistry shows expression of melanocytic markers such as melan-A, HMB45, S100, and MITF.
Reference Gallery:
Nodular melanoma. Lesion located on the trunk, with positive sentinel lymph node. A symmetrical pigmented nodule, bluish-reddish, with regular borders is observed.
Nodular melanoma. Dermoscopy shows asymmetry in colours and structures; multiple colours, including brown, blue, white, and red; irregular dots and globules; and polymorphous vessels.
Nodular melanoma. Melanoma forming closely packed small nests of non-pigmented cells.
Nodular melanoma. Closely packed, irregularly shaped aggregates of epithelioid and spindled cells with scattered mitotic figures surrounded by a fibrosing stromal reaction.
Nodular melanoma. Closely packed aggregates of monomorphic melanoma cells with an inflammatory infiltrate rich in neutrophils.
Nodular melanoma. Intradermal proliferation of neoplastic melanocytes, associated with elongated rete ridges.

Q: Microscopically, Nodular Melanoma is characterized by cohesive aggregates of [...] or spindled neoplastic melanocytes in the dermis.
Nodular melanoma. Closely packed, irregularly shaped aggregates of epithelioid and spindled cells with scattered mitotic figures surrounded by a fibrosing stromal reaction.
A: epithelioid
Back Extra: Nodular Melanoma
- Clinical: Nodular melanomas often present as rapidly growing, pigmented or unpigmented nodules that can ulcerate and bleed.
- Micro: Characterized by cohesive aggregates of epithelioid or spindled neoplastic melanocytes in the dermis, with an inflammatory infiltrate and fibrosing stromal reaction.
- Ancillary: Immunohistochemistry shows expression of melanocytic markers such as melan-A, HMB45, S100, and MITF.
Reference Gallery:
Nodular melanoma. Lesion located on the trunk, with positive sentinel lymph node. A symmetrical pigmented nodule, bluish-reddish, with regular borders is observed.
Nodular melanoma. Dermoscopy shows asymmetry in colours and structures; multiple colours, including brown, blue, white, and red; irregular dots and globules; and polymorphous vessels.
Nodular melanoma. Melanoma forming closely packed small nests of non-pigmented cells.
Nodular melanoma. Closely packed, irregularly shaped aggregates of epithelioid and spindled cells with scattered mitotic figures surrounded by a fibrosing stromal reaction.
Nodular melanoma. Closely packed aggregates of monomorphic melanoma cells with an inflammatory infiltrate rich in neutrophils.
Nodular melanoma. Intradermal proliferation of neoplastic melanocytes, associated with elongated rete ridges.

Q: In Nodular Melanoma, the dermal aggregates of neoplastic melanocytes are often accompanied by an inflammatory infiltrate and a(n) [...] stromal reaction.
Nodular melanoma. Closely packed, irregularly shaped aggregates of epithelioid and spindled cells with scattered mitotic figures surrounded by a fibrosing stromal reaction.
Nodular melanoma. Closely packed aggregates of monomorphic melanoma cells with an inflammatory infiltrate rich in neutrophils.
A: fibrosing
Back Extra: Nodular Melanoma
- Clinical: Nodular melanomas often present as rapidly growing, pigmented or unpigmented nodules that can ulcerate and bleed.
- Micro: Characterized by cohesive aggregates of epithelioid or spindled neoplastic melanocytes in the dermis, with an inflammatory infiltrate and fibrosing stromal reaction.
- Ancillary: Immunohistochemistry shows expression of melanocytic markers such as melan-A, HMB45, S100, and MITF.
Reference Gallery:
Nodular melanoma. Lesion located on the trunk, with positive sentinel lymph node. A symmetrical pigmented nodule, bluish-reddish, with regular borders is observed.
Nodular melanoma. Dermoscopy shows asymmetry in colours and structures; multiple colours, including brown, blue, white, and red; irregular dots and globules; and polymorphous vessels.
Nodular melanoma. Melanoma forming closely packed small nests of non-pigmented cells.
Nodular melanoma. Closely packed, irregularly shaped aggregates of epithelioid and spindled cells with scattered mitotic figures surrounded by a fibrosing stromal reaction.
Nodular melanoma. Closely packed aggregates of monomorphic melanoma cells with an inflammatory infiltrate rich in neutrophils.
Nodular melanoma. Intradermal proliferation of neoplastic melanocytes, associated with elongated rete ridges.

Q: A defining histologic feature of Dermal Melanoma is the presence of dense sheets of atypical melanocytes restricted to the dermis without [...], regression, or ulceration.
Dermal melanoma. Dense intradermal nodule (haematoxylin phloxine saffron stain).
Dermal melanoma. Dense dermal nodule (haematoxylin phloxine saffron stain).
A: intraepidermal involvement
Back Extra: Dermal Melanoma
- Clinical: Dermal melanoma typically presents as a solitary firm nodule, less than 10 mm in size, with variable coloration from flesh-colored to blue.
- Micro: Histologically, dermal melanoma is characterized by dense sheets of atypical melanocytes in the dermis without intraepidermal involvement, regression, or ulceration.
- Ancillary: Immunohistochemistry shows neoplastic melanocytes expressing melan-A, SOX10, HMB45, and S100, with possible mutations in GNAQ or GNA11.
Reference Gallery:
Dermal melanoma. Dense intradermal nodule (haematoxylin phloxine saffron stain).
Dermal melanoma. Dense sheets of atypical epithelioid melanocytes are seen (haematoxylin phloxine saffron stain).
Dermal melanoma. Dense dermal nodule (haematoxylin phloxine saffron stain).
Dermal melanoma. Dense sheets of atypical melanocytes with areas of necrosis and multiple mitotic figures (haematoxylin phloxine saffron stain).

Q: Dense dermal sheets of atypical epithelioid melanocytes exhibiting areas of necrosis and frequent mitotic figures are characteristic of [...].
Dermal melanoma. Dense sheets of atypical epithelioid melanocytes are seen (haematoxylin phloxine saffron stain).
Dermal melanoma. Dense sheets of atypical melanocytes with areas of necrosis and multiple mitotic figures (haematoxylin phloxine saffron stain).
A: Dermal Melanoma
Back Extra: Dermal Melanoma
- Clinical: Dermal melanoma typically presents as a solitary firm nodule, less than 10 mm in size, with variable coloration from flesh-colored to blue.
- Micro: Histologically, dermal melanoma is characterized by dense sheets of atypical melanocytes in the dermis without intraepidermal involvement, regression, or ulceration.
- Ancillary: Immunohistochemistry shows neoplastic melanocytes expressing melan-A, SOX10, HMB45, and S100, with possible mutations in GNAQ or GNA11.
Reference Gallery:
Dermal melanoma. Dense intradermal nodule (haematoxylin phloxine saffron stain).
Dermal melanoma. Dense sheets of atypical epithelioid melanocytes are seen (haematoxylin phloxine saffron stain).
Dermal melanoma. Dense dermal nodule (haematoxylin phloxine saffron stain).
Dermal melanoma. Dense sheets of atypical melanocytes with areas of necrosis and multiple mitotic figures (haematoxylin phloxine saffron stain).

Q: A crucial histologic feature that helps distinguish Spitz Melanoma from a benign Spitz nevus is its bulky extension deep into the subcutaneous fat with a complete lack of [...] at the deep margin.
Spitz melanoma. A tumour that developed on the thigh of an 11-year-old girl with an asymmetrical and ulcerated bulky neoplasm extending into subcutaneous fat. The tumour is 12 mm in diameter and 7 mm in thickness; no maturation is observed.
Spitz melanoma. Tumour from the thigh of an 11-year-old girl shows tumour extending into the subcutaneous fat without maturation; note the dense cellularity.
A: maturation
Back Extra: Spitz Melanoma
- Clinical: Patients typically present with a changing or enlarging amelanotic or pigmented papule, nodule, or plaque, typically > 6 mm, which can be pigmented and have a smooth, verrucous, or ulcerated surface.
- Micro: Spitz melanoma may demonstrate deep rather than stratified HMB45 staining, and patchy rather than diffuse melan-A staining.
- Ancillary: Spitz-associated genomic fusions (e.g., BRAF, NTRK1, ROS1, ALK, etc.) can confirm Spitz lineage.
Reference Gallery:
Spitz melanoma from a 14-year-old patient. A densely cellular melanocytic proliferation composed of junctional nests of spindle and epithelioid cells that permeate the dermis. The melanocytes have uniform round or oval nuclei, conspicuous nucleoli, and pale cytoplasm. Intradermal mitotic figures are present. The melanoma metastasized to the lungs and brain, resulting in death 18 months after initial diagnosis. This tumour carried a BRAF fusion and a TERT promoter mutation.
Spitz melanoma from a 14-year-old patient. An ulcerated epidermis with an underlying broad melanocytic neoplasm measuring 10 mm in diameter.
Spitz melanoma from a 14-year-old patient. The melanocytes have uniform round or oval nuclei, conspicuous nucleoli, and pale cytoplasm. Intradermal mitotic figures are present, with a mitotic rate of 5 mitoses per mm².
Spitz melanoma. A tumour that developed on the thigh of an 11-year-old girl with an asymmetrical and ulcerated bulky neoplasm extending into subcutaneous fat. The tumour is 12 mm in diameter and 7 mm in thickness; no maturation is observed.
Spitz melanoma. Tumour from the thigh of an 11-year-old girl shows epidermal hyperplasia and vertically oriented nests of melanocytes, suggesting a spitzoid neoplasm.
Spitz melanoma. Tumour from the thigh of an 11-year-old girl shows tumour extending into the subcutaneous fat without maturation; note the dense cellularity.
Spitz melanoma. Tumour that developed on the thigh of an 11-year-old girl at high magnification shows fascicles of spindle cells; the mitotic rate is 7 mitoses per mm², and a TERT promoter mutation was confirmed. Following the initial diagnosis, the patient developed a regional clinical lymph node metastasis at 6 months and died from widespread metastases at 24 months.

Q: While genomic evaluation of Spitz Melanoma typically confirms Spitz lineage via kinase fusions (e.g., ROS1, NTRK1, BRAF), the addition of a [...] mutation strongly correlates with highly aggressive clinical behavior and widespread metastasis.
Spitz melanoma from a 14-year-old patient. A densely cellular melanocytic proliferation composed of junctional nests of spindle and epithelioid cells that permeate the dermis. The melanocytes have uniform round or oval nuclei, conspicuous nucleoli, and pale cytoplasm. Intradermal mitotic figures are present. The melanoma metastasized to the lungs and brain, resulting in death 18 months after initial diagnosis. This tumour carried a BRAF fusion and a TERT promoter mutation.
Spitz melanoma. Tumour that developed on the thigh of an 11-year-old girl at high magnification shows fascicles of spindle cells; the mitotic rate is 7 mitoses per mm², and a TERT promoter mutation was confirmed. Following the initial diagnosis, the patient developed a regional clinical lymph node metastasis at 6 months and died from widespread metastases at 24 months.
A: TERT promoter
Back Extra: Spitz Melanoma
- Clinical: Patients typically present with a changing or enlarging amelanotic or pigmented papule, nodule, or plaque, typically > 6 mm, which can be pigmented and have a smooth, verrucous, or ulcerated surface.
- Micro: Spitz melanoma may demonstrate deep rather than stratified HMB45 staining, and patchy rather than diffuse melan-A staining.
- Ancillary: Spitz-associated genomic fusions (e.g., BRAF, NTRK1, ROS1, ALK, etc.) can confirm Spitz lineage.
Reference Gallery:
Spitz melanoma from a 14-year-old patient. A densely cellular melanocytic proliferation composed of junctional nests of spindle and epithelioid cells that permeate the dermis. The melanocytes have uniform round or oval nuclei, conspicuous nucleoli, and pale cytoplasm. Intradermal mitotic figures are present. The melanoma metastasized to the lungs and brain, resulting in death 18 months after initial diagnosis. This tumour carried a BRAF fusion and a TERT promoter mutation.
Spitz melanoma from a 14-year-old patient. An ulcerated epidermis with an underlying broad melanocytic neoplasm measuring 10 mm in diameter.
Spitz melanoma from a 14-year-old patient. The melanocytes have uniform round or oval nuclei, conspicuous nucleoli, and pale cytoplasm. Intradermal mitotic figures are present, with a mitotic rate of 5 mitoses per mm².
Spitz melanoma. A tumour that developed on the thigh of an 11-year-old girl with an asymmetrical and ulcerated bulky neoplasm extending into subcutaneous fat. The tumour is 12 mm in diameter and 7 mm in thickness; no maturation is observed.
Spitz melanoma. Tumour from the thigh of an 11-year-old girl shows epidermal hyperplasia and vertically oriented nests of melanocytes, suggesting a spitzoid neoplasm.
Spitz melanoma. Tumour from the thigh of an 11-year-old girl shows tumour extending into the subcutaneous fat without maturation; note the dense cellularity.
Spitz melanoma. Tumour that developed on the thigh of an 11-year-old girl at high magnification shows fascicles of spindle cells; the mitotic rate is 7 mitoses per mm², and a TERT promoter mutation was confirmed. Following the initial diagnosis, the patient developed a regional clinical lymph node metastasis at 6 months and died from widespread metastases at 24 months.

Q: In contrast to benign spitzoid neoplasms, Spitz Melanoma typically demonstrates a high rate of deep intradermal [...] (e.g., >5 per mm²), accompanied by cellular atypia and destructive growth.
Spitz melanoma from a 14-year-old patient. The melanocytes have uniform round or oval nuclei, conspicuous nucleoli, and pale cytoplasm. Intradermal mitotic figures are present, with a mitotic rate of 5 mitoses per mm².
Spitz melanoma. Tumour that developed on the thigh of an 11-year-old girl at high magnification shows fascicles of spindle cells; the mitotic rate is 7 mitoses per mm², and a TERT promoter mutation was confirmed. Following the initial diagnosis, the patient developed a regional clinical lymph node metastasis at 6 months and died from widespread metastases at 24 months.
A: mitotic figures
Back Extra: Spitz Melanoma
- Clinical: Patients typically present with a changing or enlarging amelanotic or pigmented papule, nodule, or plaque, typically > 6 mm, which can be pigmented and have a smooth, verrucous, or ulcerated surface.
- Micro: Spitz melanoma may demonstrate deep rather than stratified HMB45 staining, and patchy rather than diffuse melan-A staining.
- Ancillary: Spitz-associated genomic fusions (e.g., BRAF, NTRK1, ROS1, ALK, etc.) can confirm Spitz lineage.
Reference Gallery:
Spitz melanoma from a 14-year-old patient. A densely cellular melanocytic proliferation composed of junctional nests of spindle and epithelioid cells that permeate the dermis. The melanocytes have uniform round or oval nuclei, conspicuous nucleoli, and pale cytoplasm. Intradermal mitotic figures are present. The melanoma metastasized to the lungs and brain, resulting in death 18 months after initial diagnosis. This tumour carried a BRAF fusion and a TERT promoter mutation.
Spitz melanoma from a 14-year-old patient. An ulcerated epidermis with an underlying broad melanocytic neoplasm measuring 10 mm in diameter.
Spitz melanoma from a 14-year-old patient. The melanocytes have uniform round or oval nuclei, conspicuous nucleoli, and pale cytoplasm. Intradermal mitotic figures are present, with a mitotic rate of 5 mitoses per mm².
Spitz melanoma. A tumour that developed on the thigh of an 11-year-old girl with an asymmetrical and ulcerated bulky neoplasm extending into subcutaneous fat. The tumour is 12 mm in diameter and 7 mm in thickness; no maturation is observed.
Spitz melanoma. Tumour from the thigh of an 11-year-old girl shows epidermal hyperplasia and vertically oriented nests of melanocytes, suggesting a spitzoid neoplasm.
Spitz melanoma. Tumour from the thigh of an 11-year-old girl shows tumour extending into the subcutaneous fat without maturation; note the dense cellularity.
Spitz melanoma. Tumour that developed on the thigh of an 11-year-old girl at high magnification shows fascicles of spindle cells; the mitotic rate is 7 mitoses per mm², and a TERT promoter mutation was confirmed. Following the initial diagnosis, the patient developed a regional clinical lymph node metastasis at 6 months and died from widespread metastases at 24 months.

Q: In Low-CSD Melanoma (including Superficial Spreading Melanoma), the tumor often demonstrates a dual progression model, presenting initially as a flat, plaque-like radial growth phase before developing into a raised, nodular [...].
Low-CSD melanoma, superficial spreading type. This tumour has a radial growth phase component (plaque-like, predominantly tan, at the upper right of the lesion) and a vertical growth phase (raised, predominantly black).
A: vertical growth phase
Back Extra: Low-CSD Melanoma (including Superficial Spreading Melanoma)
- Clinical: Low-CSD melanoma of the superficial spreading melanoma (SSM) pattern arises as an irregularly outlined and pigmented macule that may become nodular and ulcerated as it progresses.
- Micro: The in situ component of SSM is characterized by an intraepidermal proliferation of atypical melanocytes with pagetoid scatter and variably sized nests along the dermal-epidermal junction.
- Ancillary: Neoplastic melanocytes are positive for SOX10, MITF, HMB45, melan-A (MART1), and S100, but lineage markers can be lost as the tumour progresses.
Reference Gallery:
Low-CSD melanoma (superficial spreading melanoma). Lentiginous junctional proliferation characterized by large atypical melanocytes with a pigmented cytoplasm without pagetoid scatter.
Low-CSD melanoma (superficial spreading melanoma) with an associated naevus. Large cells of the invasive vertical growth phase, top right, adjacent to smaller cells of an associated naevus.
Low-CSD melanoma (superficial spreading melanoma) with an associated naevus. Pagetoid proliferation of large atypical epithelioid cells in the epidermis.
Tumour-infiltrating lymphocyte (TIL) patterns. Schematic figure illustrating the classification of lymphocytic infiltrate patterns in vertical growth phase (VGP) melanomas, as defined by Clark and colleagues.
Low-CSD melanoma, regression features. The papillary dermis is widened with fibroplasia, and there is a sprinkling of lymphocytes and melanophages, consistent with a regressed pigmented lesion.
Superficial spreading melanoma. Radial growth phase. There are atypical melanocytes with pagetoid scatter in the epidermis, as well as clusters of cells in the dermis resembling those in the epidermis and lacking evidence of tumorigenic proliferation or mitotic activity.
Superficial spreading melanoma. Radial growth phase (left) and vertical growth phase (right). The vertical growth phase is composed of uniformly atypical cells that fill and expand the papillary dermis and infiltrate the reticular dermis. Unlike the cells of a naevus, these cells do not mature and do not disperse into the reticular dermis.
Low-CSD melanoma, superficial spreading type. This tumour has a radial growth phase component (plaque-like, predominantly tan, at the upper right of the lesion) and a vertical growth phase (raised, predominantly black).

Q: The in situ component of Low-CSD Melanoma (including Superficial Spreading Melanoma) is classically characterized by an intraepidermal proliferation of large, atypical melanocytes demonstrating upward migration, a pattern known as [...].
Low-CSD melanoma (superficial spreading melanoma) with an associated naevus. Pagetoid proliferation of large atypical epithelioid cells in the epidermis.
Superficial spreading melanoma. Radial growth phase. There are atypical melanocytes with pagetoid scatter in the epidermis, as well as clusters of cells in the dermis resembling those in the epidermis and lacking evidence of tumorigenic proliferation or mitotic activity.
A: pagetoid scatter
Back Extra: Low-CSD Melanoma (including Superficial Spreading Melanoma)
- Clinical: Low-CSD melanoma of the superficial spreading melanoma (SSM) pattern arises as an irregularly outlined and pigmented macule that may become nodular and ulcerated as it progresses.
- Micro: The in situ component of SSM is characterized by an intraepidermal proliferation of atypical melanocytes with pagetoid scatter and variably sized nests along the dermal-epidermal junction.
- Ancillary: Neoplastic melanocytes are positive for SOX10, MITF, HMB45, melan-A (MART1), and S100, but lineage markers can be lost as the tumour progresses.
Reference Gallery:
Low-CSD melanoma (superficial spreading melanoma). Lentiginous junctional proliferation characterized by large atypical melanocytes with a pigmented cytoplasm without pagetoid scatter.
Low-CSD melanoma (superficial spreading melanoma) with an associated naevus. Large cells of the invasive vertical growth phase, top right, adjacent to smaller cells of an associated naevus.
Low-CSD melanoma (superficial spreading melanoma) with an associated naevus. Pagetoid proliferation of large atypical epithelioid cells in the epidermis.
Tumour-infiltrating lymphocyte (TIL) patterns. Schematic figure illustrating the classification of lymphocytic infiltrate patterns in vertical growth phase (VGP) melanomas, as defined by Clark and colleagues.
Low-CSD melanoma, regression features. The papillary dermis is widened with fibroplasia, and there is a sprinkling of lymphocytes and melanophages, consistent with a regressed pigmented lesion.
Superficial spreading melanoma. Radial growth phase. There are atypical melanocytes with pagetoid scatter in the epidermis, as well as clusters of cells in the dermis resembling those in the epidermis and lacking evidence of tumorigenic proliferation or mitotic activity.
Superficial spreading melanoma. Radial growth phase (left) and vertical growth phase (right). The vertical growth phase is composed of uniformly atypical cells that fill and expand the papillary dermis and infiltrate the reticular dermis. Unlike the cells of a naevus, these cells do not mature and do not disperse into the reticular dermis.
Low-CSD melanoma, superficial spreading type. This tumour has a radial growth phase component (plaque-like, predominantly tan, at the upper right of the lesion) and a vertical growth phase (raised, predominantly black).

Q: During the invasive stage of Low-CSD Melanoma (including Superficial Spreading Melanoma), the atypical melanocytes expand the papillary dermis and are typically distinguished from a benign nevus by their complete lack of [...] as they descend deeper into the reticular dermis.
Low-CSD melanoma (superficial spreading melanoma) with an associated naevus. Large cells of the invasive vertical growth phase, top right, adjacent to smaller cells of an associated naevus.
Superficial spreading melanoma. Radial growth phase (left) and vertical growth phase (right). The vertical growth phase is composed of uniformly atypical cells that fill and expand the papillary dermis and infiltrate the reticular dermis. Unlike the cells of a naevus, these cells do not mature and do not disperse into the reticular dermis.
A: maturation
Back Extra: Low-CSD Melanoma (including Superficial Spreading Melanoma)
- Clinical: Low-CSD melanoma of the superficial spreading melanoma (SSM) pattern arises as an irregularly outlined and pigmented macule that may become nodular and ulcerated as it progresses.
- Micro: The in situ component of SSM is characterized by an intraepidermal proliferation of atypical melanocytes with pagetoid scatter and variably sized nests along the dermal-epidermal junction.
- Ancillary: Neoplastic melanocytes are positive for SOX10, MITF, HMB45, melan-A (MART1), and S100, but lineage markers can be lost as the tumour progresses.
Reference Gallery:
Low-CSD melanoma (superficial spreading melanoma). Lentiginous junctional proliferation characterized by large atypical melanocytes with a pigmented cytoplasm without pagetoid scatter.
Low-CSD melanoma (superficial spreading melanoma) with an associated naevus. Large cells of the invasive vertical growth phase, top right, adjacent to smaller cells of an associated naevus.
Low-CSD melanoma (superficial spreading melanoma) with an associated naevus. Pagetoid proliferation of large atypical epithelioid cells in the epidermis.
Tumour-infiltrating lymphocyte (TIL) patterns. Schematic figure illustrating the classification of lymphocytic infiltrate patterns in vertical growth phase (VGP) melanomas, as defined by Clark and colleagues.
Low-CSD melanoma, regression features. The papillary dermis is widened with fibroplasia, and there is a sprinkling of lymphocytes and melanophages, consistent with a regressed pigmented lesion.
Superficial spreading melanoma. Radial growth phase. There are atypical melanocytes with pagetoid scatter in the epidermis, as well as clusters of cells in the dermis resembling those in the epidermis and lacking evidence of tumorigenic proliferation or mitotic activity.
Superficial spreading melanoma. Radial growth phase (left) and vertical growth phase (right). The vertical growth phase is composed of uniformly atypical cells that fill and expand the papillary dermis and infiltrate the reticular dermis. Unlike the cells of a naevus, these cells do not mature and do not disperse into the reticular dermis.
Low-CSD melanoma, superficial spreading type. This tumour has a radial growth phase component (plaque-like, predominantly tan, at the upper right of the lesion) and a vertical growth phase (raised, predominantly black).

Q: In Cancer of Unknown Primary, biopsies of metastatic sites typically demonstrate a poorly differentiated morphology and frequently exhibit a [...] growth pattern, which complicates identifying the tissue of origin.
Cancer of unknown primary. Biopsy from a mass adjacent to the adrenal gland showing a poorly differentiated carcinoma with a discohesive growth pattern. A primary adrenal gland neoplasm was ruled out, and no primary tumour was identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
A: discohesive
Back Extra: Cancer of Unknown Primary
- Clinical: Cancer of unknown primary (CUP) can present with diverse symptoms such as asthenia, weight loss, pain, and swollen lymph nodes. PET-CT is used for staging single-site/oligometastatic CUP.
- Micro: In CUP, cancer cells often appear as multiple nodules with a discohesive growth pattern and poorly differentiated morphology, making it difficult to identify the primary site.
- Ancillary: NGS and immunohistochemistry panels are crucial for identifying molecular targets and ruling out other potential diagnoses. Common mutations include TP53, KRAS, and CDKN2A.
Reference Gallery:
Cancer of unknown primary. Biopsy from a mass adjacent to the adrenal gland showing a poorly differentiated carcinoma with a discohesive growth pattern. A primary adrenal gland neoplasm was ruled out, and no primary tumour was identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. A cervical lymph node biopsy contained a poorly differentiated carcinoma with a solid growth pattern and comedo-like necrosis. Squamous cell origin was ruled out, and a primary tumour was not identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. A left inguinal lymph node metastasis replaced by a poorly differentiated adenocarcinoma with biphasic morphology. A primary tumour could not be identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. An axillary soft tissue metastasis in a male patient with a poorly differentiated adenocarcinoma. A primary tumour could not be identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. CT showing a left-sided adrenal mass.
Cancer of unknown primary. CT showing left-sided cervical lymph node metastases.
Cancer of unknown primary. CT showing retroperitoneal lymph node metastases.
Cancer of unknown primary. CT showing a mediastinal mass and a left-sided rib metastasis.

Q: The fundamental defining feature of Cancer of Unknown Primary is the presence of metastatic lesions (e.g., in lymph nodes or the adrenal region) where the [...] cannot be identified despite exhaustive immunohistochemical, molecular, and radiological workup.
Cancer of unknown primary. A cervical lymph node biopsy contained a poorly differentiated carcinoma with a solid growth pattern and comedo-like necrosis. Squamous cell origin was ruled out, and a primary tumour was not identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. A left inguinal lymph node metastasis replaced by a poorly differentiated adenocarcinoma with biphasic morphology. A primary tumour could not be identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. CT showing retroperitoneal lymph node metastases.
A: primary tumor
Back Extra: Cancer of Unknown Primary
- Clinical: Cancer of unknown primary (CUP) can present with diverse symptoms such as asthenia, weight loss, pain, and swollen lymph nodes. PET-CT is used for staging single-site/oligometastatic CUP.
- Micro: In CUP, cancer cells often appear as multiple nodules with a discohesive growth pattern and poorly differentiated morphology, making it difficult to identify the primary site.
- Ancillary: NGS and immunohistochemistry panels are crucial for identifying molecular targets and ruling out other potential diagnoses. Common mutations include TP53, KRAS, and CDKN2A.
Reference Gallery:
Cancer of unknown primary. Biopsy from a mass adjacent to the adrenal gland showing a poorly differentiated carcinoma with a discohesive growth pattern. A primary adrenal gland neoplasm was ruled out, and no primary tumour was identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. A cervical lymph node biopsy contained a poorly differentiated carcinoma with a solid growth pattern and comedo-like necrosis. Squamous cell origin was ruled out, and a primary tumour was not identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. A left inguinal lymph node metastasis replaced by a poorly differentiated adenocarcinoma with biphasic morphology. A primary tumour could not be identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. An axillary soft tissue metastasis in a male patient with a poorly differentiated adenocarcinoma. A primary tumour could not be identified despite extensive immunohistochemical, radiological, and clinical workup. Broad molecular workup did not provide any information to conclude on a primary tumour site either.
Cancer of unknown primary. CT showing a left-sided adrenal mass.
Cancer of unknown primary. CT showing left-sided cervical lymph node metastases.
Cancer of unknown primary. CT showing retroperitoneal lymph node metastases.
Cancer of unknown primary. CT showing a mediastinal mass and a left-sided rib metastasis.

Q: Microscopically, Metastases to Skin typically present as relatively well-circumscribed tumor deposits expanding the dermis or subcutaneous tissue while characteristically preserving the overlying [...].
Pleural mesothelioma metastatic to the lip. Note the atypical cells expanding the dermis and preserving the overlying epidermis.
A: epidermis
Back Extra: Metastases to Skin
- Clinical: Cutaneous metastases are more common in elderly individuals, often presenting as isolated nodules or papules. In 1-12% of cases, the cutaneous metastasis is the first symptom of the malignancy.
- Micro: Metastases to the skin usually appear as relatively well-circumscribed lesions involving the dermis or subcutaneous tissue, with varying patterns depending on the primary tumor type.
- Ancillary: Immunohistochemistry is crucial for distinguishing the primary site of metastasis; metastatic adenocarcinomas to the skin are typically negative for p63, calretinin, and D2-40.
Reference Gallery:
Pleural mesothelioma metastatic to the lip. Note the atypical cells expanding the dermis and preserving the overlying epidermis.
Mucinous colonic adenocarcinoma metastatic to the skin of the abdomen. Note the characteristic pools of mucin with clusters of tumour cells inside. Inset: CDX2 immunohistochemistry.
Pleural mesothelioma metastatic to the lip. Higher-power view shows the epithelioid cells with pleomorphic nuclei, ample cytoplasm, and focal pseudoglandular pattern. Inset: Multiplex CK5/6 and WT1 immunohistochemistry.
Immunohistochemical algorithm to help in the differential diagnosis of metastasis to the skin. Legend text not found

Q: Immunohistochemistry is crucial for evaluating Metastases to Skin; to distinguish them from primary cutaneous adnexal tumors, it is helpful to note that metastatic adenocarcinomas are typically negative for calretinin, D2-40, and [...].
Immunohistochemical algorithm to help in the differential diagnosis of metastasis to the skin. Legend text not found
A: p63
Back Extra: Metastases to Skin
- Clinical: Cutaneous metastases are more common in elderly individuals, often presenting as isolated nodules or papules. In 1-12% of cases, the cutaneous metastasis is the first symptom of the malignancy.
- Micro: Metastases to the skin usually appear as relatively well-circumscribed lesions involving the dermis or subcutaneous tissue, with varying patterns depending on the primary tumor type.
- Ancillary: Immunohistochemistry is crucial for distinguishing the primary site of metastasis; metastatic adenocarcinomas to the skin are typically negative for p63, calretinin, and D2-40.
Reference Gallery:
Pleural mesothelioma metastatic to the lip. Note the atypical cells expanding the dermis and preserving the overlying epidermis.
Mucinous colonic adenocarcinoma metastatic to the skin of the abdomen. Note the characteristic pools of mucin with clusters of tumour cells inside. Inset: CDX2 immunohistochemistry.
Pleural mesothelioma metastatic to the lip. Higher-power view shows the epithelioid cells with pleomorphic nuclei, ample cytoplasm, and focal pseudoglandular pattern. Inset: Multiplex CK5/6 and WT1 immunohistochemistry.
Immunohistochemical algorithm to help in the differential diagnosis of metastasis to the skin. Legend text not found

Q: When evaluating Metastases to Skin, a histological pattern showing pools of mucin containing clusters of tumor cells that are strongly positive for CDX2 is highly characteristic of a primary [...].
Mucinous colonic adenocarcinoma metastatic to the skin of the abdomen. Note the characteristic pools of mucin with clusters of tumour cells inside. Inset: CDX2 immunohistochemistry.
A: colonic adenocarcinoma
Back Extra: Metastases to Skin
- Clinical: Cutaneous metastases are more common in elderly individuals, often presenting as isolated nodules or papules. In 1-12% of cases, the cutaneous metastasis is the first symptom of the malignancy.
- Micro: Metastases to the skin usually appear as relatively well-circumscribed lesions involving the dermis or subcutaneous tissue, with varying patterns depending on the primary tumor type.
- Ancillary: Immunohistochemistry is crucial for distinguishing the primary site of metastasis; metastatic adenocarcinomas to the skin are typically negative for p63, calretinin, and D2-40.
Reference Gallery:
Pleural mesothelioma metastatic to the lip. Note the atypical cells expanding the dermis and preserving the overlying epidermis.
Mucinous colonic adenocarcinoma metastatic to the skin of the abdomen. Note the characteristic pools of mucin with clusters of tumour cells inside. Inset: CDX2 immunohistochemistry.
Pleural mesothelioma metastatic to the lip. Higher-power view shows the epithelioid cells with pleomorphic nuclei, ample cytoplasm, and focal pseudoglandular pattern. Inset: Multiplex CK5/6 and WT1 immunohistochemistry.
Immunohistochemical algorithm to help in the differential diagnosis of metastasis to the skin. Legend text not found

Q: Clinically, an Angiolipoma characteristically presents as multiple small, [...] subcutaneous nodules, particularly on the arms of young adults.
Angiolipoma. Multiple subcutaneous nodules on the arm and forearm.
A: painful
Back Extra: Angiolipoma
- Clinical: Patients with angiolipomas typically present with multiple small, painful subcutaneous nodules, especially in children and young adults, with a male predominance.
- Micro: Angiolipomas are characterized by mature adipocytes mixed with clusters of thin-walled capillaries, often containing intravascular thrombi, and are embedded in a hyalinized stroma.
- Ancillary: Angiolipomas frequently harbor mutations in PRKD2 and PIK3CA, but molecular testing is not typically required for diagnosis.
Reference Gallery:
Angiolipoma. Angiolipomas are well-circumscribed tumours composed of mature adipose tissue with clusters of capillaries. The capillaries are predominantly located at the periphery of the tumour.
Angiolipoma. Clusters of capillaries in a hyalinized stroma associated with spindled cells are observed.
Angiolipoma. The capillaries in angiolipoma often have intravascular fibrin thrombi.
Cellular angiolipoma. In cellular angiolipomas, the vascular component predominates and there may be almost no mature adipose tissue.
Angiolipoma. Multiple subcutaneous nodules on the arm and forearm.

Q: Microscopically, an Angiolipoma consists of mature adipocytes and clusters of capillaries that typically contain characteristic intravascular [...].
Angiolipoma. Angiolipomas are well-circumscribed tumours composed of mature adipose tissue with clusters of capillaries. The capillaries are predominantly located at the periphery of the tumour.
Angiolipoma. The capillaries in angiolipoma often have intravascular fibrin thrombi.
A: fibrin thrombi
Back Extra: Angiolipoma
- Clinical: Patients with angiolipomas typically present with multiple small, painful subcutaneous nodules, especially in children and young adults, with a male predominance.
- Micro: Angiolipomas are characterized by mature adipocytes mixed with clusters of thin-walled capillaries, often containing intravascular thrombi, and are embedded in a hyalinized stroma.
- Ancillary: Angiolipomas frequently harbor mutations in PRKD2 and PIK3CA, but molecular testing is not typically required for diagnosis.
Reference Gallery:
Angiolipoma. Angiolipomas are well-circumscribed tumours composed of mature adipose tissue with clusters of capillaries. The capillaries are predominantly located at the periphery of the tumour.
Angiolipoma. Clusters of capillaries in a hyalinized stroma associated with spindled cells are observed.
Angiolipoma. The capillaries in angiolipoma often have intravascular fibrin thrombi.
Cellular angiolipoma. In cellular angiolipomas, the vascular component predominates and there may be almost no mature adipose tissue.
Angiolipoma. Multiple subcutaneous nodules on the arm and forearm.

Q: In a cellular Angiolipoma, the [...] component predominates, and there may be almost no mature adipose tissue observed.
Cellular angiolipoma. In cellular angiolipomas, the vascular component predominates and there may be almost no mature adipose tissue.
A: vascular
Back Extra: Angiolipoma
- Clinical: Patients with angiolipomas typically present with multiple small, painful subcutaneous nodules, especially in children and young adults, with a male predominance.
- Micro: Angiolipomas are characterized by mature adipocytes mixed with clusters of thin-walled capillaries, often containing intravascular thrombi, and are embedded in a hyalinized stroma.
- Ancillary: Angiolipomas frequently harbor mutations in PRKD2 and PIK3CA, but molecular testing is not typically required for diagnosis.
Reference Gallery:
Angiolipoma. Angiolipomas are well-circumscribed tumours composed of mature adipose tissue with clusters of capillaries. The capillaries are predominantly located at the periphery of the tumour.
Angiolipoma. Clusters of capillaries in a hyalinized stroma associated with spindled cells are observed.
Angiolipoma. The capillaries in angiolipoma often have intravascular fibrin thrombi.
Cellular angiolipoma. In cellular angiolipomas, the vascular component predominates and there may be almost no mature adipose tissue.
Angiolipoma. Multiple subcutaneous nodules on the arm and forearm.

Q: The morphological hallmark of an atypical lipomatous tumor is the presence of mature adipose tissue intersected by irregular fibrous septa that contain enlarged, [...].
Atypical lipomatous tumour. An irregular fibrous band containing enlarged, hyperchromatic stromal cells, the morphological hallmarks of atypical lipomatous tumour in any location.
Atypical lipomatous tumour. Adipocytes and stromal cells with enlarged, hyperchromatic nuclei in atypical lipomatous tumour. Lipoblasts are not required for this diagnosis.
A: hyperchromatic stromal cells
Back Extra: Atypical Lipomatous Tumour
- Clinical: Atypical Lipomatous Tumour (ALT) typically presents as a nonspecific nodule or mass in the dermis or subcutis, occasionally mimicking an acrochordon.
- Micro: ALT is characterized by a variable proportion of mature adipose tissue and irregular fibrous septa containing hyperchromatic stromal cells. Rare lipoblasts may be present.
- Ancillary: MDM2 nuclear expression and FISH for MDM2 amplification are useful confirmatory tests for ALT. However, ALTs associated with Li–Fraumeni syndrome are MDM2-negative but express p53.
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Atypical lipomatous tumour. An irregular fibrous band containing enlarged, hyperchromatic stromal cells, the morphological hallmarks of atypical lipomatous tumour in any location.
Atypical lipomatous tumour. Adipocytes and stromal cells with enlarged, hyperchromatic nuclei in atypical lipomatous tumour. Lipoblasts are not required for this diagnosis.

Q: Although they may be rarely seen, the presence of [...] is not required to establish the histologic diagnosis of an atypical lipomatous tumor.
Atypical lipomatous tumour. Adipocytes and stromal cells with enlarged, hyperchromatic nuclei in atypical lipomatous tumour. Lipoblasts are not required for this diagnosis.
A: lipoblasts
Back Extra: Atypical Lipomatous Tumour
- Clinical: Atypical Lipomatous Tumour (ALT) typically presents as a nonspecific nodule or mass in the dermis or subcutis, occasionally mimicking an acrochordon.
- Micro: ALT is characterized by a variable proportion of mature adipose tissue and irregular fibrous septa containing hyperchromatic stromal cells. Rare lipoblasts may be present.
- Ancillary: MDM2 nuclear expression and FISH for MDM2 amplification are useful confirmatory tests for ALT. However, ALTs associated with Li–Fraumeni syndrome are MDM2-negative but express p53.
Reference Gallery:
Atypical lipomatous tumour. An irregular fibrous band containing enlarged, hyperchromatic stromal cells, the morphological hallmarks of atypical lipomatous tumour in any location.
Atypical lipomatous tumour. Adipocytes and stromal cells with enlarged, hyperchromatic nuclei in atypical lipomatous tumour. Lipoblasts are not required for this diagnosis.

Q: The Lipoma is the most common mesenchymal neoplasm in adults. Grossly, it presents as a well-circumscribed yellow tumor, and histologically it consists of lobules of mature [...] lacking cytological atypia (e.g., no atypical hyperchromatic stromal cells).
Lipoma. Histologically, lipomas are composed of a uniform population of mature adipocytes.
Lipoma. Degenerate changes are not uncommon in lipomas, but cytological atypia, such as atypical hyperchromatic stromal cells, should be absent.
Lipoma. Macroscopically, lipoma is a well-circumscribed tumour with a uniform, glistening yellow cut surface.
A: adipocytes
Back Extra: Lipoma
- Clinical: Lipomas are the most common mesenchymal neoplasm in adults, typically presenting as slow-growing, mobile, and painless subcutaneous masses in the fifth or sixth decade.
- Micro: Histologically, lipomas are composed of lobules of mature adipocytes with thin, incomplete fibrous septa, and may show fat necrosis, fibrosis, and myxoid change.
- Ancillary: Lesional adipocytes are positive for HMGA2, which helps distinguish them from normal adipose tissue, but immunohistochemistry and molecular studies are rarely necessary for diagnosis.
Reference Gallery:
Lipoma. Histologically, lipomas are composed of a uniform population of mature adipocytes.
Lipoma. Degenerate changes are not uncommon in lipomas, but cytological atypia, such as atypical hyperchromatic stromal cells, should be absent.
Lipoma. Macroscopically, lipoma is a well-circumscribed tumour with a uniform, glistening yellow cut surface.
Osteolipoma. Longstanding lipomas may contain metaplastic bone and/or cartilage.

Q: Long-standing cases of Lipoma may undergo metaplasia to form bone and/or cartilage, a specific morphologic variant known as an [...].
Osteolipoma. Longstanding lipomas may contain metaplastic bone and/or cartilage.
A: osteolipoma
Back Extra: Lipoma
- Clinical: Lipomas are the most common mesenchymal neoplasm in adults, typically presenting as slow-growing, mobile, and painless subcutaneous masses in the fifth or sixth decade.
- Micro: Histologically, lipomas are composed of lobules of mature adipocytes with thin, incomplete fibrous septa, and may show fat necrosis, fibrosis, and myxoid change.
- Ancillary: Lesional adipocytes are positive for HMGA2, which helps distinguish them from normal adipose tissue, but immunohistochemistry and molecular studies are rarely necessary for diagnosis.
Reference Gallery:
Lipoma. Histologically, lipomas are composed of a uniform population of mature adipocytes.
Lipoma. Degenerate changes are not uncommon in lipomas, but cytological atypia, such as atypical hyperchromatic stromal cells, should be absent.
Lipoma. Macroscopically, lipoma is a well-circumscribed tumour with a uniform, glistening yellow cut surface.
Osteolipoma. Longstanding lipomas may contain metaplastic bone and/or cartilage.

Q: Histologically, Naevus lipomatosus superficialis is uniquely characterized by aggregates of mature [...] located abnormally high within the papillary and upper reticular dermis.
Naevus lipomatosus superficialis. Scanning magnification showing aggregates of adipocytes at the level of the papillary and upper reticular dermis.
Naevus lipomatosus superficialis. Higher magnification showing aggregates of mature adipocytes.
A: adipocytes
Back Extra: Naevus lipomatosus superficialis
- Clinical: Naevus lipomatosus superficialis (NLS) presents as slow-growing, skin-coloured to yellow, dome-shaped plaques with a wrinkled or cerebriform overlying skin.
- Micro: NLS is characterized by aggregates of mature adipocytes at the level of the papillary and upper reticular dermis, often surrounding blood vessels.
- Ancillary: Ancillary studies are not typically required for diagnosis; the diagnosis is primarily based on clinical and histopathological findings.
Reference Gallery:
Naevus lipomatosus superficialis. Scanning magnification showing aggregates of adipocytes at the level of the papillary and upper reticular dermis.
Naevus lipomatosus superficialis. Higher magnification showing aggregates of mature adipocytes.
Naevus lipomatosus superficialis. Soft nodules with a zosteriform distribution on the lateral trunk and lower back.

Q: Clinically, Naevus lipomatosus superficialis often presents as soft, skin-colored to yellow nodules or plaques that frequently cluster in a [...] distribution on the lower back and lateral trunk.
Naevus lipomatosus superficialis. Soft nodules with a zosteriform distribution on the lateral trunk and lower back.
A: zosteriform
Back Extra: Naevus lipomatosus superficialis
- Clinical: Naevus lipomatosus superficialis (NLS) presents as slow-growing, skin-coloured to yellow, dome-shaped plaques with a wrinkled or cerebriform overlying skin.
- Micro: NLS is characterized by aggregates of mature adipocytes at the level of the papillary and upper reticular dermis, often surrounding blood vessels.
- Ancillary: Ancillary studies are not typically required for diagnosis; the diagnosis is primarily based on clinical and histopathological findings.
Reference Gallery:
Naevus lipomatosus superficialis. Scanning magnification showing aggregates of adipocytes at the level of the papillary and upper reticular dermis.
Naevus lipomatosus superficialis. Higher magnification showing aggregates of mature adipocytes.
Naevus lipomatosus superficialis. Soft nodules with a zosteriform distribution on the lateral trunk and lower back.

Q: The histologic diagnosis of pleomorphic liposarcoma requires identifying [...] set within a background of undifferentiated, high-grade spindle cell sarcoma.
Pleomorphic liposarcoma. Dermal pleomorphic liposarcoma composed of an undifferentiated spindle cell sarcoma containing numerous pleomorphic lipoblasts.
Pleomorphic liposarcoma. Diagnosis requires the presence of pleomorphic lipoblasts. Note lipid droplets indenting the pleomorphic, hyperchromatic nucleus. These cells may be rare or plentiful in any given tumour.
A: pleomorphic lipoblasts
Back Extra: Pleomorphic Liposarcoma
- Clinical: Patients present with a rapidly growing, nonspecific or occasionally fatty-appearing mass of the skin or subcutis, typically in adults in later life.
- Micro: The tumours contain a variable number of pleomorphic lipoblasts in a background of undifferentiated, high-grade, pleomorphic spindle cell sarcoma.
- Ancillary: Absence of MDM2 amplification with a complex karyotype and widespread complex copy-number changes may help in the diagnosis.
Reference Gallery:
Pleomorphic liposarcoma. Dermal pleomorphic liposarcoma composed of an undifferentiated spindle cell sarcoma containing numerous pleomorphic lipoblasts.
Pleomorphic liposarcoma. Diagnosis requires the presence of pleomorphic lipoblasts. Note lipid droplets indenting the pleomorphic, hyperchromatic nucleus. These cells may be rare or plentiful in any given tumour.
Pleomorphic liposarcoma. Epithelioid morphology resembling that of poorly differentiated carcinoma, adrenocortical carcinoma, melanoma, high-grade myxoid (round cell) liposarcoma, or renal clear cell carcinoma may be seen in a subset of cases.
Pleomorphic liposarcoma. Areas resembling myxofibrosarcoma are an infrequent finding in subcutaneous pleomorphic liposarcomas.

Q: A subset of pleomorphic liposarcoma cases may feature a striking [...] morphology, which can microscopically mimic poorly differentiated carcinoma, melanoma, or renal clear cell carcinoma.
Pleomorphic liposarcoma. Epithelioid morphology resembling that of poorly differentiated carcinoma, adrenocortical carcinoma, melanoma, high-grade myxoid (round cell) liposarcoma, or renal clear cell carcinoma may be seen in a subset of cases.
A: epithelioid
Back Extra: Pleomorphic Liposarcoma
- Clinical: Patients present with a rapidly growing, nonspecific or occasionally fatty-appearing mass of the skin or subcutis, typically in adults in later life.
- Micro: The tumours contain a variable number of pleomorphic lipoblasts in a background of undifferentiated, high-grade, pleomorphic spindle cell sarcoma.
- Ancillary: Absence of MDM2 amplification with a complex karyotype and widespread complex copy-number changes may help in the diagnosis.
Reference Gallery:
Pleomorphic liposarcoma. Dermal pleomorphic liposarcoma composed of an undifferentiated spindle cell sarcoma containing numerous pleomorphic lipoblasts.
Pleomorphic liposarcoma. Diagnosis requires the presence of pleomorphic lipoblasts. Note lipid droplets indenting the pleomorphic, hyperchromatic nucleus. These cells may be rare or plentiful in any given tumour.
Pleomorphic liposarcoma. Epithelioid morphology resembling that of poorly differentiated carcinoma, adrenocortical carcinoma, melanoma, high-grade myxoid (round cell) liposarcoma, or renal clear cell carcinoma may be seen in a subset of cases.
Pleomorphic liposarcoma. Areas resembling myxofibrosarcoma are an infrequent finding in subcutaneous pleomorphic liposarcomas.

Q: Although primarily an undifferentiated spindle cell tumor, subcutaneous cases of pleomorphic liposarcoma may infrequently contain areas morphologically resembling [...].
Pleomorphic liposarcoma. Areas resembling myxofibrosarcoma are an infrequent finding in subcutaneous pleomorphic liposarcomas.
A: myxofibrosarcoma
Back Extra: Pleomorphic Liposarcoma
- Clinical: Patients present with a rapidly growing, nonspecific or occasionally fatty-appearing mass of the skin or subcutis, typically in adults in later life.
- Micro: The tumours contain a variable number of pleomorphic lipoblasts in a background of undifferentiated, high-grade, pleomorphic spindle cell sarcoma.
- Ancillary: Absence of MDM2 amplification with a complex karyotype and widespread complex copy-number changes may help in the diagnosis.
Reference Gallery:
Pleomorphic liposarcoma. Dermal pleomorphic liposarcoma composed of an undifferentiated spindle cell sarcoma containing numerous pleomorphic lipoblasts.
Pleomorphic liposarcoma. Diagnosis requires the presence of pleomorphic lipoblasts. Note lipid droplets indenting the pleomorphic, hyperchromatic nucleus. These cells may be rare or plentiful in any given tumour.
Pleomorphic liposarcoma. Epithelioid morphology resembling that of poorly differentiated carcinoma, adrenocortical carcinoma, melanoma, high-grade myxoid (round cell) liposarcoma, or renal clear cell carcinoma may be seen in a subset of cases.
Pleomorphic liposarcoma. Areas resembling myxofibrosarcoma are an infrequent finding in subcutaneous pleomorphic liposarcomas.

Q: In the pleomorphic variant of Spindle Cell / Pleomorphic Lipoma, histology characteristically demonstrates pleomorphic spindle cells and multinucleated [...] giant cells.
Pleomorphic lipoma. Features of spindle cell lipoma with the addition of pleomorphic cells and multinucleated floret-like giant cells.
A: floret-like
Back Extra: Spindle Cell / Pleomorphic Lipoma
- Clinical: Patients with Spindle Cell / Pleomorphic Lipoma (SCL/PL) usually present with a painless, slowly growing, mobile subcutaneous mass, most common in men aged 45 to 60 years.
- Micro: SCL/PL is characterized by mature adipocytes, bland spindle cells, and ropy collagen. PL also shows pleomorphic spindle cells and multinucleated floret-like giant cells.
- Ancillary: CD34 positivity in spindle and pleomorphic cells, with loss of nuclear RB1, and partial or whole chromosome 13 and/or 16 deletions are typical ancillary findings.
Reference Gallery:
Spindle cell lipoma. A variable combination of adipocytes, bland spindle cells, and ropy collagen fibres.
Pleomorphic lipoma. Features of spindle cell lipoma with the addition of pleomorphic cells and multinucleated floret-like giant cells.
Myxoid spindle cell lipoma. Bland spindle cells, ropy collagen, and mature adipocytes in an extensively myxoid stroma.
Spindle cell lipoma. Pseudoangiomatous pattern.
Spindle cell lipoma. Low-fat pattern with bland spindle cells, ropy collagen, and little to no adipose component.

Q: A hallmark histologic feature of Spindle Cell / Pleomorphic Lipoma is the presence of bland spindle cells and thick, eosinophilic bundles of [...], often admixed with mature adipocytes.
Spindle cell lipoma. A variable combination of adipocytes, bland spindle cells, and ropy collagen fibres.
Spindle cell lipoma. Low-fat pattern with bland spindle cells, ropy collagen, and little to no adipose component.
A: ropy collagen
Back Extra: Spindle Cell / Pleomorphic Lipoma
- Clinical: Patients with Spindle Cell / Pleomorphic Lipoma (SCL/PL) usually present with a painless, slowly growing, mobile subcutaneous mass, most common in men aged 45 to 60 years.
- Micro: SCL/PL is characterized by mature adipocytes, bland spindle cells, and ropy collagen. PL also shows pleomorphic spindle cells and multinucleated floret-like giant cells.
- Ancillary: CD34 positivity in spindle and pleomorphic cells, with loss of nuclear RB1, and partial or whole chromosome 13 and/or 16 deletions are typical ancillary findings.
Reference Gallery:
Spindle cell lipoma. A variable combination of adipocytes, bland spindle cells, and ropy collagen fibres.
Pleomorphic lipoma. Features of spindle cell lipoma with the addition of pleomorphic cells and multinucleated floret-like giant cells.
Myxoid spindle cell lipoma. Bland spindle cells, ropy collagen, and mature adipocytes in an extensively myxoid stroma.
Spindle cell lipoma. Pseudoangiomatous pattern.
Spindle cell lipoma. Low-fat pattern with bland spindle cells, ropy collagen, and little to no adipose component.

Q: Patients with [...] may present with multiple Ungual Fibrokeratomas (often referred to as Koenen tumors), which frequently cause longitudinal grooves in the affected nail plates.
Ungual fibrokeratoma. This patient with tuberous sclerosis shows multiple ungual fibrokeratomas / Koenen tumours affecting the fingernails. The tumours are associated with longitudinal grooves in the affected nail plates.
A: tuberous sclerosis
Back Extra: Ungual Fibrokeratoma
- Clinical: Ungual fibrokeratomas often appear as rod-shaped, dome-shaped, flat, or branching lesions and are frequently associated with longitudinal grooves in the nail plate, trachyonychia, and onycholysis.
- Micro: Histopathology shows a fibrovascular core with epidermal acanthosis and hyperkeratosis. Histopathological patterns vary, ranging from dense collagen bundles to oedematous structures.
- Ancillary: Immunohistochemistry is generally not required, but factor XIIIa-positive dermal dendritic cells are involved in the pathogenesis of these lesions.
Reference Gallery:
Ungual fibrokeratoma. The sections show a sausage-shaped lesion that demonstrates a fibrovascular core and has epidermal acanthosis and hyperkeratosis.
Ungual fibrokeratoma. The sections show a sausage-shaped lesion that demonstrates a fibrovascular core and has epidermal acanthosis and hyperkeratosis.
Ungual fibrokeratoma. This patient with tuberous sclerosis shows multiple ungual fibrokeratomas / Koenen tumours affecting the fingernails. The tumours are associated with longitudinal grooves in the affected nail plates.

Q: The histopathologic hallmark of an Ungual Fibrokeratoma is a sausage-shaped lesion demonstrating a central [...] surrounded by epidermal acanthosis and hyperkeratosis.
Ungual fibrokeratoma. The sections show a sausage-shaped lesion that demonstrates a fibrovascular core and has epidermal acanthosis and hyperkeratosis.
Ungual fibrokeratoma. The sections show a sausage-shaped lesion that demonstrates a fibrovascular core and has epidermal acanthosis and hyperkeratosis.
A: fibrovascular core
Back Extra: Ungual Fibrokeratoma
- Clinical: Ungual fibrokeratomas often appear as rod-shaped, dome-shaped, flat, or branching lesions and are frequently associated with longitudinal grooves in the nail plate, trachyonychia, and onycholysis.
- Micro: Histopathology shows a fibrovascular core with epidermal acanthosis and hyperkeratosis. Histopathological patterns vary, ranging from dense collagen bundles to oedematous structures.
- Ancillary: Immunohistochemistry is generally not required, but factor XIIIa-positive dermal dendritic cells are involved in the pathogenesis of these lesions.
Reference Gallery:
Ungual fibrokeratoma. The sections show a sausage-shaped lesion that demonstrates a fibrovascular core and has epidermal acanthosis and hyperkeratosis.
Ungual fibrokeratoma. The sections show a sausage-shaped lesion that demonstrates a fibrovascular core and has epidermal acanthosis and hyperkeratosis.
Ungual fibrokeratoma. This patient with tuberous sclerosis shows multiple ungual fibrokeratomas / Koenen tumours affecting the fingernails. The tumours are associated with longitudinal grooves in the affected nail plates.

Q: A [...] typically manifests as a dome-shaped, sessile papule on the nose or central face, demonstrating dilated blood vessels and a collagenized stroma on histology.
Fibrous papule. A papular shape of a classic fibrous papule.
Fibrous papule. Hyalinized collagen is seen in the upper dermis, with dilated blood vessels and stellate fibroblasts.
A: Fibrous Papule
Back Extra: Fibrous Papule
- Clinical: Fibrous papule typically manifests as a dome-shaped, sessile papule on the nose or central face, most commonly seen in middle-aged adults.
- Micro: Characterized by a dome-shaped configuration with dilated blood vessels, fibrotic or collagenized stroma, and stellate fibroblasts.
- Ancillary: Multiple fibrous papules in tuberous sclerosis are associated with germline mutations in TSC1 or TSC2 genes.
Reference Gallery:
Fibrous papule. A papular shape of a classic fibrous papule.
Fibrous papule. Hyalinized collagen is seen in the upper dermis, with dilated blood vessels and stellate fibroblasts.
Fibrous papule. Higher-power view of the stellate fibroblasts and the dilated blood vessels in the upper dermis.
Fibrous papule. Some lesions are more cellular.
Fibrous papule. Some lesions have a clear cell pattern.

Q: At high power, the hyalinized collagen stroma of a Fibrous Papule characteristically contains dilated blood vessels and scattered [...] fibroblasts.
Fibrous papule. Hyalinized collagen is seen in the upper dermis, with dilated blood vessels and stellate fibroblasts.
Fibrous papule. Higher-power view of the stellate fibroblasts and the dilated blood vessels in the upper dermis.
A: stellate
Back Extra: Fibrous Papule
- Clinical: Fibrous papule typically manifests as a dome-shaped, sessile papule on the nose or central face, most commonly seen in middle-aged adults.
- Micro: Characterized by a dome-shaped configuration with dilated blood vessels, fibrotic or collagenized stroma, and stellate fibroblasts.
- Ancillary: Multiple fibrous papules in tuberous sclerosis are associated with germline mutations in TSC1 or TSC2 genes.
Reference Gallery:
Fibrous papule. A papular shape of a classic fibrous papule.
Fibrous papule. Hyalinized collagen is seen in the upper dermis, with dilated blood vessels and stellate fibroblasts.
Fibrous papule. Higher-power view of the stellate fibroblasts and the dilated blood vessels in the upper dermis.
Fibrous papule. Some lesions are more cellular.
Fibrous papule. Some lesions have a clear cell pattern.

Q: While a typical Fibrous Papule contains scattered stellate fibroblasts in a fibrotic stroma, histologic variants exist that are more cellular or display a distinct [...] pattern.
Fibrous papule. Some lesions are more cellular.
Fibrous papule. Some lesions have a clear cell pattern.
A: clear cell
Back Extra: Fibrous Papule
- Clinical: Fibrous papule typically manifests as a dome-shaped, sessile papule on the nose or central face, most commonly seen in middle-aged adults.
- Micro: Characterized by a dome-shaped configuration with dilated blood vessels, fibrotic or collagenized stroma, and stellate fibroblasts.
- Ancillary: Multiple fibrous papules in tuberous sclerosis are associated with germline mutations in TSC1 or TSC2 genes.
Reference Gallery:
Fibrous papule. A papular shape of a classic fibrous papule.
Fibrous papule. Hyalinized collagen is seen in the upper dermis, with dilated blood vessels and stellate fibroblasts.
Fibrous papule. Higher-power view of the stellate fibroblasts and the dilated blood vessels in the upper dermis.
Fibrous papule. Some lesions are more cellular.
Fibrous papule. Some lesions have a clear cell pattern.

Q: Histologically, Angiomatoid Fibrous Histiocytoma is characterized by nodules of ovoid and spindle cells, a peripheral rim of lymphocytes with germinal centers, and characteristic [...].
Angiomatoid fibrous histiocytoma. A well-circumscribed, nodular tumour with a blood-filled pseudocystic space, tumour cells, inflammatory cells, and a peripheral cuff of lymphoid cells (including germinal centres), resembling a lymph node.
Angiomatoid fibrous histiocytoma. Pseudocystic haemorrhagic areas surrounded by epithelioid and spindle-shaped tumour cells and intervening lymphocytes and plasma cells.
A: hemorrhagic pseudocystic spaces
Back Extra: Angiomatoid Fibrous Histiocytoma
- Clinical: Angiomatoid fibrous histiocytoma typically presents as a slow-growing, superficial, painless soft tissue mass, commonly affecting the subcutis in the first two decades of life.
- Micro: The histopathology is characterized by nodules of ovoid and spindle cells, haemorrhagic pseudocystic spaces, and a peripheral rim of lymphoplasmacytic cells with germinal centres.
- Ancillary: Immunohistochemistry often shows positivity for SOX9 and desmin, and the presence of EWSR1::CREB1 or EWSR1::ATF1 gene fusions is a key diagnostic feature.
Reference Gallery:
Angiomatoid fibrous histiocytoma. A well-circumscribed, nodular tumour with a blood-filled pseudocystic space, tumour cells, inflammatory cells, and a peripheral cuff of lymphoid cells (including germinal centres), resembling a lymph node.
Angiomatoid fibrous histiocytoma. Pseudocystic haemorrhagic areas surrounded by epithelioid and spindle-shaped tumour cells and intervening lymphocytes and plasma cells.
Angiomatoid fibrous histiocytoma. Fascicles of epithelioid and spindled cells with bland nuclei and a variable myxoid stroma.
Angiomatoid fibrous histiocytoma. Oval and polygonal cells with distinct areas of myxoid stroma and intervening lymphocytes and plasma cells.
Angiomatoid fibrous histiocytoma. Tumour cells have enlarged nuclei and relatively bland chromatin, along with interspersed lymphocytes and few plasma cells.
Angiomatoid fibrous histiocytoma. Tumour cells displaying focal desmin positivity.
Angiomatoid fibrous histiocytoma. Using an EWSR1 dual-coloured break-apart FISH probe, several tumour cells show red–green split signals, indicative of EWSR1 gene rearrangement.

Q: In addition to focal desmin positivity, a key molecular diagnostic feature of Angiomatoid Fibrous Histiocytoma is the presence of an [...] gene rearrangement (usually fused with CREB1 or ATF1).
Angiomatoid fibrous histiocytoma. Tumour cells displaying focal desmin positivity.
Angiomatoid fibrous histiocytoma. Using an EWSR1 dual-coloured break-apart FISH probe, several tumour cells show red–green split signals, indicative of EWSR1 gene rearrangement.
A: EWSR1
Back Extra: Angiomatoid Fibrous Histiocytoma
- Clinical: Angiomatoid fibrous histiocytoma typically presents as a slow-growing, superficial, painless soft tissue mass, commonly affecting the subcutis in the first two decades of life.
- Micro: The histopathology is characterized by nodules of ovoid and spindle cells, haemorrhagic pseudocystic spaces, and a peripheral rim of lymphoplasmacytic cells with germinal centres.
- Ancillary: Immunohistochemistry often shows positivity for SOX9 and desmin, and the presence of EWSR1::CREB1 or EWSR1::ATF1 gene fusions is a key diagnostic feature.
Reference Gallery:
Angiomatoid fibrous histiocytoma. A well-circumscribed, nodular tumour with a blood-filled pseudocystic space, tumour cells, inflammatory cells, and a peripheral cuff of lymphoid cells (including germinal centres), resembling a lymph node.
Angiomatoid fibrous histiocytoma. Pseudocystic haemorrhagic areas surrounded by epithelioid and spindle-shaped tumour cells and intervening lymphocytes and plasma cells.
Angiomatoid fibrous histiocytoma. Fascicles of epithelioid and spindled cells with bland nuclei and a variable myxoid stroma.
Angiomatoid fibrous histiocytoma. Oval and polygonal cells with distinct areas of myxoid stroma and intervening lymphocytes and plasma cells.
Angiomatoid fibrous histiocytoma. Tumour cells have enlarged nuclei and relatively bland chromatin, along with interspersed lymphocytes and few plasma cells.
Angiomatoid fibrous histiocytoma. Tumour cells displaying focal desmin positivity.
Angiomatoid fibrous histiocytoma. Using an EWSR1 dual-coloured break-apart FISH probe, several tumour cells show red–green split signals, indicative of EWSR1 gene rearrangement.

Q: Histologically, Atypical Fibroxanthoma is a highly cellular dermal tumor that frequently displays extreme nuclear pleomorphism, brisk mitoses, and bizarre [...] cells.
Atypical fibroxanthoma. Multinucleated tumour cells and mitoses are frequently identifiable.
A: multinucleated
Back Extra: Atypical Fibroxanthoma
- Clinical: Atypical Fibroxanthoma (AFX) often manifests as a solitary, localized nodule up to 20 mm in diameter, on sun-damaged skin, with common ulceration and a short history of rapid growth.
- Micro: AFX is characterized by a highly cellular dermal tumour with nuclear pleomorphism, mitoses, and spindle or epithelioid cells. It may show various patterns including granular cell, keloidal, myxoid, and sclerotic forms.
- Ancillary: Immunohistochemistry is essential for diagnosis, with CD10 often strongly and diffusely expressed. AFX should be CD10-positive and negative for melanocyte and keratinocyte markers.
Reference Gallery:
Atypical fibroxanthoma. Multinucleated tumour cells and mitoses are frequently identifiable.
Atypical fibroxanthoma. This tumour shows keloidal change; in other zones, the lesion was almost entirely composed of eosinophilic collagen fibres, with only very sparse remaining malignant cells.
Atypical fibroxanthoma. This example of atypical fibroxanthoma exhibits granular cells with haemorrhage and pigmentation due to haemosiderin deposition.
Atypical fibroxanthoma. Extensive haemorrhage in atypical fibroxanthoma sometimes raises the differential diagnosis of angiosarcoma.
Atypical fibroxanthoma. Myxoid subtype.
Atypical fibroxanthoma. Plaque-like pattern, with cells lying parallel to the epidermis. Centrally, this tumour showed features more typical of atypical fibroxanthoma, with a nodule invading deep into the dermis.
Atypical fibroxanthoma. SMA positivity is frequent.

Q: A notable histologic pattern of Atypical Fibroxanthoma features thick, densely eosinophilic collagen fibers with sparse malignant cells, referred to as [...] change.
Atypical fibroxanthoma. This tumour shows keloidal change; in other zones, the lesion was almost entirely composed of eosinophilic collagen fibres, with only very sparse remaining malignant cells.
A: keloidal
Back Extra: Atypical Fibroxanthoma
- Clinical: Atypical Fibroxanthoma (AFX) often manifests as a solitary, localized nodule up to 20 mm in diameter, on sun-damaged skin, with common ulceration and a short history of rapid growth.
- Micro: AFX is characterized by a highly cellular dermal tumour with nuclear pleomorphism, mitoses, and spindle or epithelioid cells. It may show various patterns including granular cell, keloidal, myxoid, and sclerotic forms.
- Ancillary: Immunohistochemistry is essential for diagnosis, with CD10 often strongly and diffusely expressed. AFX should be CD10-positive and negative for melanocyte and keratinocyte markers.
Reference Gallery:
Atypical fibroxanthoma. Multinucleated tumour cells and mitoses are frequently identifiable.
Atypical fibroxanthoma. This tumour shows keloidal change; in other zones, the lesion was almost entirely composed of eosinophilic collagen fibres, with only very sparse remaining malignant cells.
Atypical fibroxanthoma. This example of atypical fibroxanthoma exhibits granular cells with haemorrhage and pigmentation due to haemosiderin deposition.
Atypical fibroxanthoma. Extensive haemorrhage in atypical fibroxanthoma sometimes raises the differential diagnosis of angiosarcoma.
Atypical fibroxanthoma. Myxoid subtype.
Atypical fibroxanthoma. Plaque-like pattern, with cells lying parallel to the epidermis. Centrally, this tumour showed features more typical of atypical fibroxanthoma, with a nodule invading deep into the dermis.
Atypical fibroxanthoma. SMA positivity is frequent.

Q: When Atypical Fibroxanthoma presents with extensive [...], the pseudovascular spaces and pleomorphic cells can histologically mimic an angiosarcoma.
Atypical fibroxanthoma. Extensive haemorrhage in atypical fibroxanthoma sometimes raises the differential diagnosis of angiosarcoma.
A: hemorrhage
Back Extra: Atypical Fibroxanthoma
- Clinical: Atypical Fibroxanthoma (AFX) often manifests as a solitary, localized nodule up to 20 mm in diameter, on sun-damaged skin, with common ulceration and a short history of rapid growth.
- Micro: AFX is characterized by a highly cellular dermal tumour with nuclear pleomorphism, mitoses, and spindle or epithelioid cells. It may show various patterns including granular cell, keloidal, myxoid, and sclerotic forms.
- Ancillary: Immunohistochemistry is essential for diagnosis, with CD10 often strongly and diffusely expressed. AFX should be CD10-positive and negative for melanocyte and keratinocyte markers.
Reference Gallery:
Atypical fibroxanthoma. Multinucleated tumour cells and mitoses are frequently identifiable.
Atypical fibroxanthoma. This tumour shows keloidal change; in other zones, the lesion was almost entirely composed of eosinophilic collagen fibres, with only very sparse remaining malignant cells.
Atypical fibroxanthoma. This example of atypical fibroxanthoma exhibits granular cells with haemorrhage and pigmentation due to haemosiderin deposition.
Atypical fibroxanthoma. Extensive haemorrhage in atypical fibroxanthoma sometimes raises the differential diagnosis of angiosarcoma.
Atypical fibroxanthoma. Myxoid subtype.
Atypical fibroxanthoma. Plaque-like pattern, with cells lying parallel to the epidermis. Centrally, this tumour showed features more typical of atypical fibroxanthoma, with a nodule invading deep into the dermis.
Atypical fibroxanthoma. SMA positivity is frequent.

Q: Calcifying aponeurotic fibroma typically features bland spindle cells in fascicles surrounding nodular zones of [...], which may contain scattered epithelioid cells, chondroid cells, and osteoclast-like giant cells.
Calcifying aponeurotic fibroma. Spindle cells arranged in fascicles surround areas of calcification containing epithelioid and chondroid cells and occasional multinucleated osteoclast-like giant cells.
Calcifying aponeurotic fibroma. Calcifying aponeurotic fibroma is characterized by bland spindle cells and nodular zones of calcification.
A: calcification
Back Extra: Calcifying Aponeurotic Fibroma
- Clinical: Calcifying Aponeurotic Fibroma typically presents as a solitary painless mass in the aponeurotic soft tissue of the palms and feet.
- Micro: Calcifying Aponeurotic Fibroma is characterized by bland spindle cells arranged in fascicles, with areas of calcification and occasional multinucleated giant cells.
- Ancillary: Detection of FN1::EGF fusion, resulting from a recurrent translocation involving the promoter region of FN1 (2q35) and EGF (4q25), is helpful in diagnosing Calcifying Aponeurotic Fibroma.
Reference Gallery:
Calcifying aponeurotic fibroma. Spindle cells arranged in fascicles surround areas of calcification containing epithelioid and chondroid cells and occasional multinucleated osteoclast-like giant cells.
Calcifying aponeurotic fibroma. A resection specimen showing an ill-defined greyish-white lesion with a gritty consistency.
Calcifying aponeurotic fibroma. The infiltrative spindle cell component is reminiscent of fibromatosis.
Calcifying aponeurotic fibroma. Calcifying aponeurotic fibroma is characterized by bland spindle cells and nodular zones of calcification.

Q: Histologically, the infiltrative spindle cell component of calcifying aponeurotic fibroma is strongly reminiscent of [...].
Calcifying aponeurotic fibroma. The infiltrative spindle cell component is reminiscent of fibromatosis.
A: fibromatosis
Back Extra: Calcifying Aponeurotic Fibroma
- Clinical: Calcifying Aponeurotic Fibroma typically presents as a solitary painless mass in the aponeurotic soft tissue of the palms and feet.
- Micro: Calcifying Aponeurotic Fibroma is characterized by bland spindle cells arranged in fascicles, with areas of calcification and occasional multinucleated giant cells.
- Ancillary: Detection of FN1::EGF fusion, resulting from a recurrent translocation involving the promoter region of FN1 (2q35) and EGF (4q25), is helpful in diagnosing Calcifying Aponeurotic Fibroma.
Reference Gallery:
Calcifying aponeurotic fibroma. Spindle cells arranged in fascicles surround areas of calcification containing epithelioid and chondroid cells and occasional multinucleated osteoclast-like giant cells.
Calcifying aponeurotic fibroma. A resection specimen showing an ill-defined greyish-white lesion with a gritty consistency.
Calcifying aponeurotic fibroma. The infiltrative spindle cell component is reminiscent of fibromatosis.
Calcifying aponeurotic fibroma. Calcifying aponeurotic fibroma is characterized by bland spindle cells and nodular zones of calcification.

Q: Grossly, calcifying aponeurotic fibroma typically presents as an ill-defined, grayish-white mass with a characteristic [...] consistency.
Calcifying aponeurotic fibroma. A resection specimen showing an ill-defined greyish-white lesion with a gritty consistency.
A: gritty
Back Extra: Calcifying Aponeurotic Fibroma
- Clinical: Calcifying Aponeurotic Fibroma typically presents as a solitary painless mass in the aponeurotic soft tissue of the palms and feet.
- Micro: Calcifying Aponeurotic Fibroma is characterized by bland spindle cells arranged in fascicles, with areas of calcification and occasional multinucleated giant cells.
- Ancillary: Detection of FN1::EGF fusion, resulting from a recurrent translocation involving the promoter region of FN1 (2q35) and EGF (4q25), is helpful in diagnosing Calcifying Aponeurotic Fibroma.
Reference Gallery:
Calcifying aponeurotic fibroma. Spindle cells arranged in fascicles surround areas of calcification containing epithelioid and chondroid cells and occasional multinucleated osteoclast-like giant cells.
Calcifying aponeurotic fibroma. A resection specimen showing an ill-defined greyish-white lesion with a gritty consistency.
Calcifying aponeurotic fibroma. The infiltrative spindle cell component is reminiscent of fibromatosis.
Calcifying aponeurotic fibroma. Calcifying aponeurotic fibroma is characterized by bland spindle cells and nodular zones of calcification.

Q: Microscopically, Cutaneous Myxoma is characterized by a well-circumscribed papulonodular lesion featuring abundant myxoid material and sparse stromal cells that classically exhibit a [...] morphology.
Cutaneous myxoma. Scanning magnification showing a papulonodular lesion with a myxoid appearance.
Cutaneous myxoma. Higher magnification showing myxoid material, with sparse cellularity. The stromal cells have fusiform or stellate morphology.
A: spindled or stellate
Q: Cutaneous Myxoma
- Clinical: Cutaneous myxomas manifest as [...], often due to abundant mucin content. Multiple lesions may indicate Carney complex.
- Micro: Cutaneous myxoma is characterized by a [...]. Adnexal induction in the overlying epidermis is common in Carney complex.
- Ancillary: Immunohistochemistry shows positivity for [...] and loss of expression of PRKAR1A in sporadic cases. In Carney complex, PRKAR1A gene mutations are found.
Reference Gallery:
Cutaneous myxoma. Scanning magnification showing a papulonodular lesion with a myxoid appearance.
Cutaneous myxoma. Higher magnification showing myxoid material, with sparse cellularity. The stromal cells have fusiform or stellate morphology.
A: slow-growing nodules with a translucent appearance; well-circumscribed multilobular lesion with abundant myxoid material and spindled or stellate cells; α-SMA

Q: While they can occur sporadically, the clinical finding of multiple Cutaneous Myxomas should raise strong suspicion for an underlying diagnosis of [...].
Cutaneous myxoma. Scanning magnification showing a papulonodular lesion with a myxoid appearance.
A: Carney complex
Q: Cutaneous Myxoma
- Clinical: Cutaneous myxomas manifest as [...], often due to abundant mucin content. Multiple lesions may indicate Carney complex.
- Micro: Cutaneous myxoma is characterized by a [...]. Adnexal induction in the overlying epidermis is common in Carney complex.
- Ancillary: Immunohistochemistry shows positivity for [...] and loss of expression of PRKAR1A in sporadic cases. In Carney complex, PRKAR1A gene mutations are found.
Reference Gallery:
Cutaneous myxoma. Scanning magnification showing a papulonodular lesion with a myxoid appearance.
Cutaneous myxoma. Higher magnification showing myxoid material, with sparse cellularity. The stromal cells have fusiform or stellate morphology.
A: slow-growing nodules with a translucent appearance; well-circumscribed multilobular lesion with abundant myxoid material and spindled or stellate cells; α-SMA

Q: Clinically, a Dermatofibroma presents as a firm, dome-shaped, and often hyperpigmented papule that characteristically retracts downward when laterally squeezed, demonstrating a positive [...].
Dermatofibroma. Symmetrical, firm papulonodule with a peripheral brown rim.
A: dimple sign
Back Extra: Dermatofibroma
- Clinical: Dermatofibroma is a common, benign, firm, dome-shaped papule or nodule, often hyperpigmented with a characteristic 'dimple sign' when squeezed.
- Micro: Characterized by a polymorphous population of spindled to rounded cells with surrounding reactive dermal dendrocytes and macrophages, and entrapment of collagen bundles forming collagen balls.
- Ancillary: Immunohistochemistry shows focally positive staining for CD68, SMA, desmin, and CD34. Recurrent gene fusions involving PKC isoforms are identified in a minority of cases.
Reference Gallery:
Dermatofibroma. Symmetrical, firm papulonodule with a peripheral brown rim.
Dermatofibroma. Classic dermatofibroma, centred in the reticular dermis, with a symmetrical outline.
Cellular dermatofibroma. Densely packed spindled cells.
Atypical Dermatofibroma. Pleomorphic and spindled cells.
Dermatofibroma. An older lesion, with spindled and triangular cells with coarse collagen.
Dermatofibroma. With foamy macrophages.
Atypical Dermatofibroma. With pleomorphic giant cells.
Dermatofibroma. With spindled cells and macrophages, coarse collagen, and collagen balls.

Q: A classic histologic hallmark of Dermatofibroma is a polymorphous proliferation of spindled cells in the dermis that entraps coarse bundles of collagen at the periphery, frequently forming [...].
Dermatofibroma. Classic dermatofibroma, centred in the reticular dermis, with a symmetrical outline.
Dermatofibroma. An older lesion, with spindled and triangular cells with coarse collagen.
Dermatofibroma. With spindled cells and macrophages, coarse collagen, and collagen balls.
A: collagen balls
Back Extra: Dermatofibroma
- Clinical: Dermatofibroma is a common, benign, firm, dome-shaped papule or nodule, often hyperpigmented with a characteristic 'dimple sign' when squeezed.
- Micro: Characterized by a polymorphous population of spindled to rounded cells with surrounding reactive dermal dendrocytes and macrophages, and entrapment of collagen bundles forming collagen balls.
- Ancillary: Immunohistochemistry shows focally positive staining for CD68, SMA, desmin, and CD34. Recurrent gene fusions involving PKC isoforms are identified in a minority of cases.
Reference Gallery:
Dermatofibroma. Symmetrical, firm papulonodule with a peripheral brown rim.
Dermatofibroma. Classic dermatofibroma, centred in the reticular dermis, with a symmetrical outline.
Cellular dermatofibroma. Densely packed spindled cells.
Atypical Dermatofibroma. Pleomorphic and spindled cells.
Dermatofibroma. An older lesion, with spindled and triangular cells with coarse collagen.
Dermatofibroma. With foamy macrophages.
Atypical Dermatofibroma. With pleomorphic giant cells.
Dermatofibroma. With spindled cells and macrophages, coarse collagen, and collagen balls.

Q: Microscopically, Dermatofibrosarcoma Protuberans is a cellular tumor composed of uniform short spindle cells arranged in a prominent [...] (cartwheel) pattern, which classically infiltrates subcutaneous fat in a "honeycomb" fashion.
Dermatofibrosarcoma protuberans. Cellular tumour composed of monotonous short spindle cells with prominent storiform growth pattern.
Dermatofibrosarcoma protuberans. Tumour characteristically infiltrates around fat cells (“honeycomb pattern”).
A: storiform
Back Extra: Dermatofibrosarcoma Protuberans
- Clinical: Patients typically present with a painless, firm, slow-growing plaque or nodule, which may be discoloured (brown, reddish-blue, or violaceous).
- Micro: Characterized by a proliferation of uniform, medium-sized spindle cells with a storiform or cartwheel pattern, centered in the dermis and infiltrating the subcutaneous adipose tissue in a lace-like or honeycomb pattern.
- Ancillary: The majority of cases harbour a COL1A1::PDGFB rearrangement, detected by FISH, and show diffuse strong staining for CD34.
Reference Gallery:
Dermatofibrosarcoma protuberans. Polypoid tumour on the arm.
Dermatofibrosarcoma protuberans. Cross-section reveals a white, firm, fibrous tumour.
Dermatofibrosarcoma protuberans. Cellular, dermally based tumour that infiltrates into the subcutaneous fat.
Dermatofibrosarcoma protuberans. Cellular tumour composed of monotonous short spindle cells with prominent storiform growth pattern.
Dermatofibrosarcoma protuberans. Tumour characteristically infiltrates around fat cells (“honeycomb pattern”).
Dermatofibrosarcoma protuberans with fibrosarcomatous transformation. In fibrosarcomatous transformation, the spindle cells are longer, arranged in a fascicular/herringbone-like pattern, and often accompanied by increased mitotic activity.
Dermatofibrosarcoma protuberans. Giant cell fibroblastoma subtype with multinucleated giant cells.
Dermatofibrosarcoma protuberans. Some tumours can have prominent myxoid stroma and lose their storiform architecture.
Dermatofibrosarcoma protuberans. Myoid nodules can be rarely encountered.
Dermatofibrosarcoma protuberans. The pigmented subtype has pigment-laden dendritic cells.
Dermatofibrosarcoma protuberans. The majority of tumours harbour a t(17;22) translocation resulting in a fusion of PDGFB with the promoter region of COL1A1 via multiple breakpoints. The resulting protein is constitutively expressed and processed to a normal PDGFB ligand, driving oncogenesis.

Q: The pathogenesis of Dermatofibrosarcoma Protuberans is classically driven by a t(17;22) translocation that results in a [PDGFB] gene fusion.
Dermatofibrosarcoma protuberans. The majority of tumours harbour a t(17;22) translocation resulting in a fusion of PDGFB with the promoter region of COL1A1 via multiple breakpoints. The resulting protein is constitutively expressed and processed to a normal PDGFB ligand, driving oncogenesis.
A: COL1A1
Back Extra: Dermatofibrosarcoma Protuberans
- Clinical: Patients typically present with a painless, firm, slow-growing plaque or nodule, which may be discoloured (brown, reddish-blue, or violaceous).
- Micro: Characterized by a proliferation of uniform, medium-sized spindle cells with a storiform or cartwheel pattern, centered in the dermis and infiltrating the subcutaneous adipose tissue in a lace-like or honeycomb pattern.
- Ancillary: The majority of cases harbour a COL1A1::PDGFB rearrangement, detected by FISH, and show diffuse strong staining for CD34.
Reference Gallery:
Dermatofibrosarcoma protuberans. Polypoid tumour on the arm.
Dermatofibrosarcoma protuberans. Cross-section reveals a white, firm, fibrous tumour.
Dermatofibrosarcoma protuberans. Cellular, dermally based tumour that infiltrates into the subcutaneous fat.
Dermatofibrosarcoma protuberans. Cellular tumour composed of monotonous short spindle cells with prominent storiform growth pattern.
Dermatofibrosarcoma protuberans. Tumour characteristically infiltrates around fat cells (“honeycomb pattern”).
Dermatofibrosarcoma protuberans with fibrosarcomatous transformation. In fibrosarcomatous transformation, the spindle cells are longer, arranged in a fascicular/herringbone-like pattern, and often accompanied by increased mitotic activity.
Dermatofibrosarcoma protuberans. Giant cell fibroblastoma subtype with multinucleated giant cells.
Dermatofibrosarcoma protuberans. Some tumours can have prominent myxoid stroma and lose their storiform architecture.
Dermatofibrosarcoma protuberans. Myoid nodules can be rarely encountered.
Dermatofibrosarcoma protuberans. The pigmented subtype has pigment-laden dendritic cells.
Dermatofibrosarcoma protuberans. The majority of tumours harbour a t(17;22) translocation resulting in a fusion of PDGFB with the promoter region of COL1A1 via multiple breakpoints. The resulting protein is constitutively expressed and processed to a normal PDGFB ligand, driving oncogenesis.

Q: When Dermatofibrosarcoma Protuberans undergoes fibrosarcomatous transformation, the spindle cells become longer and are arranged in a highly cellular [...] (or fascicular) growth pattern with increased mitotic activity.
Dermatofibrosarcoma protuberans with fibrosarcomatous transformation. In fibrosarcomatous transformation, the spindle cells are longer, arranged in a fascicular/herringbone-like pattern, and often accompanied by increased mitotic activity.
A: herringbone
Back Extra: Dermatofibrosarcoma Protuberans
- Clinical: Patients typically present with a painless, firm, slow-growing plaque or nodule, which may be discoloured (brown, reddish-blue, or violaceous).
- Micro: Characterized by a proliferation of uniform, medium-sized spindle cells with a storiform or cartwheel pattern, centered in the dermis and infiltrating the subcutaneous adipose tissue in a lace-like or honeycomb pattern.
- Ancillary: The majority of cases harbour a COL1A1::PDGFB rearrangement, detected by FISH, and show diffuse strong staining for CD34.
Reference Gallery:
Dermatofibrosarcoma protuberans. Polypoid tumour on the arm.
Dermatofibrosarcoma protuberans. Cross-section reveals a white, firm, fibrous tumour.
Dermatofibrosarcoma protuberans. Cellular, dermally based tumour that infiltrates into the subcutaneous fat.
Dermatofibrosarcoma protuberans. Cellular tumour composed of monotonous short spindle cells with prominent storiform growth pattern.
Dermatofibrosarcoma protuberans. Tumour characteristically infiltrates around fat cells (“honeycomb pattern”).
Dermatofibrosarcoma protuberans with fibrosarcomatous transformation. In fibrosarcomatous transformation, the spindle cells are longer, arranged in a fascicular/herringbone-like pattern, and often accompanied by increased mitotic activity.
Dermatofibrosarcoma protuberans. Giant cell fibroblastoma subtype with multinucleated giant cells.
Dermatofibrosarcoma protuberans. Some tumours can have prominent myxoid stroma and lose their storiform architecture.
Dermatofibrosarcoma protuberans. Myoid nodules can be rarely encountered.
Dermatofibrosarcoma protuberans. The pigmented subtype has pigment-laden dendritic cells.
Dermatofibrosarcoma protuberans. The majority of tumours harbour a t(17;22) translocation resulting in a fusion of PDGFB with the promoter region of COL1A1 via multiple breakpoints. The resulting protein is constitutively expressed and processed to a normal PDGFB ligand, driving oncogenesis.

Q: Histologically, Dermatomyofibroma is characterized by bundles of bland myofibroblasts arranged parallel to the epidermis, except in the deep dermis and subcutis where they typically assume a [...] arrangement while sparing adnexal structures.
Dermatomyofibroma. A dermal neoplasm composed of bundles of myofibroblasts arranged parallel to the epidermis except in the deep dermis/subcutis, where the arrangement is usually perpendicular.
Dermatomyofibroma. Bland myofibroblasts arranged in bundles are seen. Note the sparing of adnexal structures.
A: perpendicular
Back Extra: Dermatomyofibroma
- Clinical: Dermatomyofibroma most frequently occurs in young females and presents as an asymptomatic, erythematous, reddish-brown or hypopigmented, flat, plaque-like lesion.
- Micro: Histologically, the lesion shows densely packed slender bundles of cytologically bland spindle cells with fibroblastic and myofibroblastic differentiation, arranged parallel to the epidermis, except in the deep dermis/subcutis where the arrangement is usually perpendicular.
- Ancillary: Immunohistochemically, tumour cells are positive for vimentin and calponin, and may show variable positivity for α-SMA and CD34, while desmin, h-caldesmon, and S100 are negative.
Reference Gallery:
Dermatomyofibroma. A dermal neoplasm composed of bundles of myofibroblasts arranged parallel to the epidermis except in the deep dermis/subcutis, where the arrangement is usually perpendicular.
Dermatomyofibroma. Bland myofibroblasts arranged in bundles are seen. Note the sparing of adnexal structures.
Dermatomyofibroma. The tumour cells may be positive for SMA, particularly in early lesions.

Q: In Dermatomyofibroma, the tumor cells typically express vimentin and calponin, and may be positive for [...] (particularly in early lesions), while desmin, h-caldesmon, and S100 are negative.
Dermatomyofibroma. The tumour cells may be positive for SMA, particularly in early lesions.
A: SMA
Back Extra: Dermatomyofibroma
- Clinical: Dermatomyofibroma most frequently occurs in young females and presents as an asymptomatic, erythematous, reddish-brown or hypopigmented, flat, plaque-like lesion.
- Micro: Histologically, the lesion shows densely packed slender bundles of cytologically bland spindle cells with fibroblastic and myofibroblastic differentiation, arranged parallel to the epidermis, except in the deep dermis/subcutis where the arrangement is usually perpendicular.
- Ancillary: Immunohistochemically, tumour cells are positive for vimentin and calponin, and may show variable positivity for α-SMA and CD34, while desmin, h-caldesmon, and S100 are negative.
Reference Gallery:
Dermatomyofibroma. A dermal neoplasm composed of bundles of myofibroblasts arranged parallel to the epidermis except in the deep dermis/subcutis, where the arrangement is usually perpendicular.
Dermatomyofibroma. Bland myofibroblasts arranged in bundles are seen. Note the sparing of adnexal structures.
Dermatomyofibroma. The tumour cells may be positive for SMA, particularly in early lesions.

Q: The characteristic microscopic appearance of Desmoplastic Fibroblastoma consists of a hypocellular tumor with bland, widely spaced [...] embedded in a fibromyxoid to collagenous stroma.
Desmoplastic fibroblastoma. Hypocellular proliferation of distinctive, widely spaced, spindled to stellate fibroblasts in a fibromyxoid stroma.
Desmoplastic fibroblastoma. Hypocellular hyalinization with bland stellate fibroblasts.
A: spindled to stellate fibroblasts
Back Extra: Desmoplastic Fibroblastoma
- Clinical: Desmoplastic fibroblastoma is a painless, solitary, slow-growing subcutaneous mass that predominantly affects adults (median age: 50–60 years) with a male predominance.
- Micro: Hypocellular tumours with bland, spindled to stellate fibroblasts in a fibromyxoid to delicate collagenous background.
- Ancillary: Translocations involving 11q12, including t(2;11)(q31;q12) and t(11;17)(q12;p11.2), have been reported, with overexpression of the FOSL1 protein.
Reference Gallery:
Desmoplastic fibroblastoma. Hypocellular proliferation of distinctive, widely spaced, spindled to stellate fibroblasts in a fibromyxoid stroma.
Desmoplastic fibroblastoma. Hypocellular hyalinization with bland stellate fibroblasts.

Q: At low magnification, Desmoplastic Fibroblastoma is characteristically a remarkably [...] tumor, containing widely dispersed fibroblasts within a fibromyxoid or hyalinized stroma.
Desmoplastic fibroblastoma. Hypocellular proliferation of distinctive, widely spaced, spindled to stellate fibroblasts in a fibromyxoid stroma.
Desmoplastic fibroblastoma. Hypocellular hyalinization with bland stellate fibroblasts.
A: hypocellular
Back Extra: Desmoplastic Fibroblastoma
- Clinical: Desmoplastic fibroblastoma is a painless, solitary, slow-growing subcutaneous mass that predominantly affects adults (median age: 50–60 years) with a male predominance.
- Micro: Hypocellular tumours with bland, spindled to stellate fibroblasts in a fibromyxoid to delicate collagenous background.
- Ancillary: Translocations involving 11q12, including t(2;11)(q31;q12) and t(11;17)(q12;p11.2), have been reported, with overexpression of the FOSL1 protein.
Reference Gallery:
Desmoplastic fibroblastoma. Hypocellular proliferation of distinctive, widely spaced, spindled to stellate fibroblasts in a fibromyxoid stroma.
Desmoplastic fibroblastoma. Hypocellular hyalinization with bland stellate fibroblasts.

Q: Elastofibroma is a slow-growing lesion characterized microscopically by bland spindle cells, a myxoid stroma, and characteristic degenerative, fragmented [...].
Elastofibroma. Degenerative fragmented collagen fibres with bland spindle cells.
A: collagen fibers
Back Extra: Elastofibroma
- Clinical: Elastofibromas are slow-growing, typically solitary, and usually asymptomatic, but can cause pain or scapular snapping/impingement.
- Micro: Elastofibromas are characterized by degenerative collagen fibres, bland spindle cells, and a myxoid stroma.
- Ancillary: Chromosomal abnormalities such as copy gains on Xq and t(8;12)(q22;q24.3) rearrangements have been identified in some cases.
Reference Gallery:
Elastofibroma. Degenerative fragmented collagen fibres with bland spindle cells.
Elastofibroma. Elastin stain highlights fragmented, thickened, and globular collagen fibres.

Q: To best highlight the fragmented, thickened, and globular fibers characteristic of an Elastofibroma, an [...] stain is utilized.
Elastofibroma. Elastin stain highlights fragmented, thickened, and globular collagen fibres.
A: elastin
Back Extra: Elastofibroma
- Clinical: Elastofibromas are slow-growing, typically solitary, and usually asymptomatic, but can cause pain or scapular snapping/impingement.
- Micro: Elastofibromas are characterized by degenerative collagen fibres, bland spindle cells, and a myxoid stroma.
- Ancillary: Chromosomal abnormalities such as copy gains on Xq and t(8;12)(q22;q24.3) rearrangements have been identified in some cases.
Reference Gallery:
Elastofibroma. Degenerative fragmented collagen fibres with bland spindle cells.
Elastofibroma. Elastin stain highlights fragmented, thickened, and globular collagen fibres.

Q: Morphologically, Epithelioid fibrous histiocytoma presents as a well-circumscribed, dome-shaped papule often featuring a characteristic epidermal [...], and is composed of uniform plump cells with abundant pale eosinophilic to amphophilic cytoplasm.
Epithelioid fibrous histiocytoma. Scanning magnification showing a well-circumscribed dome-shaped papule with adnexal collarette.
Epithelioid fibrous histiocytoma. Higher magnification showing tumour cells with vesicular nuclei, small nucleoli, and abundant pale eosinophilic or amphophilic cytoplasm.
A: adnexal collarette
Back Extra: Epithelioid fibrous histiocytoma
- Clinical: Epithelioid fibrous histiocytoma typically presents as an exophytic nodule, often with a vascular appearance, commonly affecting the lower extremities and occurring in young to middle-aged adults (median age: 40 years).
- Micro: The lesion is well-circumscribed, often with an adnexal collarette, and composed of uniform plump epithelioid cells with vesicular nuclei, small nucleoli, and abundant pale eosinophilic or amphophilic cytoplasm.
- Ancillary: ALK overexpression is seen in about 90% of cases, with ALK rearrangements being the most common genetic alteration.
Reference Gallery:
Epithelioid fibrous histiocytoma. Scanning magnification showing a well-circumscribed dome-shaped papule with adnexal collarette.
Epithelioid fibrous histiocytoma. Higher magnification showing tumour cells with vesicular nuclei, small nucleoli, and abundant pale eosinophilic or amphophilic cytoplasm.
Epithelioid fibrous histiocytoma. Immunohistochemically, the neoplastic cells show strong ALK positivity.

Q: Immunohistochemically, approximately 90% of Epithelioid fibrous histiocytoma cases show strong, diffuse positivity for [...], reflecting underlying gene rearrangements.
Epithelioid fibrous histiocytoma. Immunohistochemically, the neoplastic cells show strong ALK positivity.
A: ALK
Back Extra: Epithelioid fibrous histiocytoma
- Clinical: Epithelioid fibrous histiocytoma typically presents as an exophytic nodule, often with a vascular appearance, commonly affecting the lower extremities and occurring in young to middle-aged adults (median age: 40 years).
- Micro: The lesion is well-circumscribed, often with an adnexal collarette, and composed of uniform plump epithelioid cells with vesicular nuclei, small nucleoli, and abundant pale eosinophilic or amphophilic cytoplasm.
- Ancillary: ALK overexpression is seen in about 90% of cases, with ALK rearrangements being the most common genetic alteration.
Reference Gallery:
Epithelioid fibrous histiocytoma. Scanning magnification showing a well-circumscribed dome-shaped papule with adnexal collarette.
Epithelioid fibrous histiocytoma. Higher magnification showing tumour cells with vesicular nuclei, small nucleoli, and abundant pale eosinophilic or amphophilic cytoplasm.
Epithelioid fibrous histiocytoma. Immunohistochemically, the neoplastic cells show strong ALK positivity.

Q: Histologically, EWSR1::SMAD3-rearranged fibroblastic tumors are well-demarcated with a characteristic zonal architecture, featuring an acellular, hyalinized [...] surrounded by a cellular periphery of intersecting spindle cell fascicles.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. Peripheral zones consist of intersecting cellular fascicles of fibroblastic spindle cells within collagenous stroma.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. The acellular centre of the tumour may be hyalinized.
A: center
Back Extra: EWSR1::SMAD3-rearranged fibroblastic tumour
- Clinical: EWSR1::SMAD3-rearranged fibroblastic tumours typically present as small, painless, superficial lesions on the hands and feet, with a female predominance (M:F ratio: 1:4).
- Micro: These tumours are well-demarcated, with a hyalinized acellular centre and intersecting cellular fascicles of fibroblastic spindle cells in the periphery.
- Ancillary: Diagnosis is confirmed by the presence of an EWSR1::SMAD3 fusion gene, detectable by next-generation sequencing or break-apart FISH assays.
Reference Gallery:
EWSR1::SMAD3 fusion–positive fibroblastic tumour. Peripheral zones consist of intersecting cellular fascicles of fibroblastic spindle cells within collagenous stroma.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. Tumour area with hyalinized collagen rosettes.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. The acellular centre of the tumour may be hyalinized.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. By immunohistochemistry, tumour cells consistently show diffuse nuclear ERG expression.

Q: An important diagnostic pitfall is that EWSR1::SMAD3-rearranged fibroblastic tumors consistently demonstrate diffuse nuclear immunohistochemical expression of [...], which can mimic vascular neoplasms.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. By immunohistochemistry, tumour cells consistently show diffuse nuclear ERG expression.
A: ERG
Back Extra: EWSR1::SMAD3-rearranged fibroblastic tumour
- Clinical: EWSR1::SMAD3-rearranged fibroblastic tumours typically present as small, painless, superficial lesions on the hands and feet, with a female predominance (M:F ratio: 1:4).
- Micro: These tumours are well-demarcated, with a hyalinized acellular centre and intersecting cellular fascicles of fibroblastic spindle cells in the periphery.
- Ancillary: Diagnosis is confirmed by the presence of an EWSR1::SMAD3 fusion gene, detectable by next-generation sequencing or break-apart FISH assays.
Reference Gallery:
EWSR1::SMAD3 fusion–positive fibroblastic tumour. Peripheral zones consist of intersecting cellular fascicles of fibroblastic spindle cells within collagenous stroma.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. Tumour area with hyalinized collagen rosettes.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. The acellular centre of the tumour may be hyalinized.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. By immunohistochemistry, tumour cells consistently show diffuse nuclear ERG expression.

Q: In addition to a biphasic zonal architecture, a distinctive microscopic feature frequently observed in EWSR1::SMAD3-rearranged fibroblastic tumors is the presence of hyalinized collagen [...].
EWSR1::SMAD3 fusion–positive fibroblastic tumour. Tumour area with hyalinized collagen rosettes.
A: rosettes
Back Extra: EWSR1::SMAD3-rearranged fibroblastic tumour
- Clinical: EWSR1::SMAD3-rearranged fibroblastic tumours typically present as small, painless, superficial lesions on the hands and feet, with a female predominance (M:F ratio: 1:4).
- Micro: These tumours are well-demarcated, with a hyalinized acellular centre and intersecting cellular fascicles of fibroblastic spindle cells in the periphery.
- Ancillary: Diagnosis is confirmed by the presence of an EWSR1::SMAD3 fusion gene, detectable by next-generation sequencing or break-apart FISH assays.
Reference Gallery:
EWSR1::SMAD3 fusion–positive fibroblastic tumour. Peripheral zones consist of intersecting cellular fascicles of fibroblastic spindle cells within collagenous stroma.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. Tumour area with hyalinized collagen rosettes.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. The acellular centre of the tumour may be hyalinized.
EWSR1::SMAD3 fusion–positive fibroblastic tumour. By immunohistochemistry, tumour cells consistently show diffuse nuclear ERG expression.

Q: Histologically, [...] features a dermal proliferation of bland, spindle-shaped and ovoid cells in short intersecting fascicles, characteristically demonstrating preserved adnexal structures and scattered, entrapped adipocytes.
Fibroblastic connective tissue naevus. The spindled cells are arranged in fascicles and have bland, undulating nuclei and eosinophilic cytoplasmic processes. Scattered adipocytes in the reticular dermis are a frequent finding.
Fibroblastic connective tissue naevus. Same lesion shown in <<34144>> at higher magnification. Note that adnexal structures are well preserved, and some adipocytes are entrapped in the tumour. Here cells are arranged in a storiform manner.
A: Fibroblastic Connective Tissue Naevus
Back Extra: Fibroblastic Connective Tissue Naevus
- Clinical: Fibroblastic Connective Tissue Naevus typically manifests as a solitary, slowly growing, painless plaque-like or nodular skin lesion, most commonly in young patients (median age: 10 years) with a slight female predominance.
- Micro: The lesion is composed of bland spindle-shaped and ovoid cells arranged in a short intersecting fascicular pattern, with preserved adnexal structures and entrapped adipocytes.
- Ancillary: Expression of CD34 and SMA is common, and the KHDRBS1::NTRK3 rearrangement has been reported in one case.
Reference Gallery:
Fibroblastic connective tissue naevus. Mild papillomatosis of the epidermis and a proliferation of bland spindled cells in the dermis are observed. Note the presence of adipocytes in the reticular dermis.
Fibroblastic connective tissue naevus. The spindled cells are arranged in fascicles and have bland, undulating nuclei and eosinophilic cytoplasmic processes. Scattered adipocytes in the reticular dermis are a frequent finding.
Fibroblastic connective tissue naevus. Intersecting fascicles of bland spindled cells are seen.
Fibroblastic connective tissue naevus. Atrophic congenital plaque on the back.
Fibroblastic connective tissue naevus. Foci of short bland ovoid cells in the reticular dermis are seen, especially around the eccrine glands, sparing them (haematoxylin eosin saffron stain).
Fibroblastic connective tissue naevus. The lesion is positive for CD34.
Fibroblastic connective tissue naevus. Short spindle or ovoid cells are observed (haematoxylin eosin saffron stain).
Fibroblastic connective tissue naevus. Cellular infiltration of both the reticular dermis and the subcutis. Spindle-shaped and ovoid cells are arranged in a short intersecting fascicular pattern.
Fibroblastic connective tissue naevus. Same lesion shown in <<34144>> at higher magnification. Note that adnexal structures are well preserved, and some adipocytes are entrapped in the tumour. Here cells are arranged in a storiform manner.

Q: Immunohistochemical staining in Fibroblastic Connective Tissue Naevus typically demonstrates common expression of SMA and [...] within the lesional spindled cells.
Fibroblastic connective tissue naevus. The lesion is positive for CD34.
A: CD34
Back Extra: Fibroblastic Connective Tissue Naevus
- Clinical: Fibroblastic Connective Tissue Naevus typically manifests as a solitary, slowly growing, painless plaque-like or nodular skin lesion, most commonly in young patients (median age: 10 years) with a slight female predominance.
- Micro: The lesion is composed of bland spindle-shaped and ovoid cells arranged in a short intersecting fascicular pattern, with preserved adnexal structures and entrapped adipocytes.
- Ancillary: Expression of CD34 and SMA is common, and the KHDRBS1::NTRK3 rearrangement has been reported in one case.
Reference Gallery:
Fibroblastic connective tissue naevus. Mild papillomatosis of the epidermis and a proliferation of bland spindled cells in the dermis are observed. Note the presence of adipocytes in the reticular dermis.
Fibroblastic connective tissue naevus. The spindled cells are arranged in fascicles and have bland, undulating nuclei and eosinophilic cytoplasmic processes. Scattered adipocytes in the reticular dermis are a frequent finding.
Fibroblastic connective tissue naevus. Intersecting fascicles of bland spindled cells are seen.
Fibroblastic connective tissue naevus. Atrophic congenital plaque on the back.
Fibroblastic connective tissue naevus. Foci of short bland ovoid cells in the reticular dermis are seen, especially around the eccrine glands, sparing them (haematoxylin eosin saffron stain).
Fibroblastic connective tissue naevus. The lesion is positive for CD34.
Fibroblastic connective tissue naevus. Short spindle or ovoid cells are observed (haematoxylin eosin saffron stain).
Fibroblastic connective tissue naevus. Cellular infiltration of both the reticular dermis and the subcutis. Spindle-shaped and ovoid cells are arranged in a short intersecting fascicular pattern.
Fibroblastic connective tissue naevus. Same lesion shown in <<34144>> at higher magnification. Note that adnexal structures are well preserved, and some adipocytes are entrapped in the tumour. Here cells are arranged in a storiform manner.

Q: Clinically, [...] typically presents in young children (median age of 10 years) as a solitary, slowly growing, painless plaque or nodular lesion.
Fibroblastic connective tissue naevus. Atrophic congenital plaque on the back.
A: Fibroblastic Connective Tissue Naevus
Back Extra: Fibroblastic Connective Tissue Naevus
- Clinical: Fibroblastic Connective Tissue Naevus typically manifests as a solitary, slowly growing, painless plaque-like or nodular skin lesion, most commonly in young patients (median age: 10 years) with a slight female predominance.
- Micro: The lesion is composed of bland spindle-shaped and ovoid cells arranged in a short intersecting fascicular pattern, with preserved adnexal structures and entrapped adipocytes.
- Ancillary: Expression of CD34 and SMA is common, and the KHDRBS1::NTRK3 rearrangement has been reported in one case.
Reference Gallery:
Fibroblastic connective tissue naevus. Mild papillomatosis of the epidermis and a proliferation of bland spindled cells in the dermis are observed. Note the presence of adipocytes in the reticular dermis.
Fibroblastic connective tissue naevus. The spindled cells are arranged in fascicles and have bland, undulating nuclei and eosinophilic cytoplasmic processes. Scattered adipocytes in the reticular dermis are a frequent finding.
Fibroblastic connective tissue naevus. Intersecting fascicles of bland spindled cells are seen.
Fibroblastic connective tissue naevus. Atrophic congenital plaque on the back.
Fibroblastic connective tissue naevus. Foci of short bland ovoid cells in the reticular dermis are seen, especially around the eccrine glands, sparing them (haematoxylin eosin saffron stain).
Fibroblastic connective tissue naevus. The lesion is positive for CD34.
Fibroblastic connective tissue naevus. Short spindle or ovoid cells are observed (haematoxylin eosin saffron stain).
Fibroblastic connective tissue naevus. Cellular infiltration of both the reticular dermis and the subcutis. Spindle-shaped and ovoid cells are arranged in a short intersecting fascicular pattern.
Fibroblastic connective tissue naevus. Same lesion shown in <<34144>> at higher magnification. Note that adnexal structures are well preserved, and some adipocytes are entrapped in the tumour. Here cells are arranged in a storiform manner.

Q: Fibroma of tendon sheath is a sharply circumscribed, hypocellular tumor characterized by bland fibroblasts and characteristic [...] vascular spaces within a dense hyalinized matrix.
Fibroma of tendon sheath. Sharply circumscribed hypocellular tumour with a hyalinized matrix containing slit-like spaces and blood vessels.
Fibroma of tendon sheath. Bland fibroblasts and slit-like capillary vessels within a hyalinized matrix.
A: slit-like
Back Extra: Fibroma of tendon sheath
- Clinical: Fibroma of tendon sheath typically presents as a small, slow-growing, and solitary mass in the upper extremities, often asymptomatic to mildly painful, and is more common in middle-aged men.
- Micro: Characterized by bland fibroblastic spindle and stellate cells arranged in fascicles or a storiform pattern within a dense fibrocollagenous hyalinized matrix, with slit-like spaces and dilated vascular channels.
- Ancillary: USP6 rearrangement can support the diagnosis in challenging cases.
Reference Gallery:
Fibroma of tendon sheath. Sharply circumscribed hypocellular tumour with a hyalinized matrix containing slit-like spaces and blood vessels.
Fibroma of tendon sheath. Bland fibroblasts and slit-like capillary vessels within a hyalinized matrix.
Cellular fibroma of tendon sheath. Example showing foci of increased cellularity, with constituent spindle cells arrayed in a fascicular to storiform growth pattern resembling nodular fasciitis.

Q: Fibroma of tendon sheath can exhibit foci of increased cellularity, featuring spindle cells arrayed in a fascicular to [...] growth pattern that morphologically resembles nodular fasciitis.
Cellular fibroma of tendon sheath. Example showing foci of increased cellularity, with constituent spindle cells arrayed in a fascicular to storiform growth pattern resembling nodular fasciitis.
A: storiform
Back Extra: Fibroma of tendon sheath
- Clinical: Fibroma of tendon sheath typically presents as a small, slow-growing, and solitary mass in the upper extremities, often asymptomatic to mildly painful, and is more common in middle-aged men.
- Micro: Characterized by bland fibroblastic spindle and stellate cells arranged in fascicles or a storiform pattern within a dense fibrocollagenous hyalinized matrix, with slit-like spaces and dilated vascular channels.
- Ancillary: USP6 rearrangement can support the diagnosis in challenging cases.
Reference Gallery:
Fibroma of tendon sheath. Sharply circumscribed hypocellular tumour with a hyalinized matrix containing slit-like spaces and blood vessels.
Fibroma of tendon sheath. Bland fibroblasts and slit-like capillary vessels within a hyalinized matrix.
Cellular fibroma of tendon sheath. Example showing foci of increased cellularity, with constituent spindle cells arrayed in a fascicular to storiform growth pattern resembling nodular fasciitis.

Q: Clinically, Inclusion Body Fibromatosis typically presents as an asymptomatic, dome-shaped cutaneous nodule located on the hands or feet, particularly involving the [...].
Inclusion body fibromatosis. A single protuberant nodule with an erythematous surface on the lateral aspect of the distal fourth toe.
Inclusion body fibromatosis. Dome-shaped cellular dermal nodule composed of spindled cells arranged in short fascicles and whorls.
A: distal digits
Back Extra: Inclusion Body Fibromatosis
- Clinical: Inclusion Body Fibromatosis typically presents as an asymptomatic, dome-shaped or polypoid cutaneous nodule on the hands or feet, especially the distal digits.
- Micro: Characterized by spindled cells with elongated, bland nuclei and eosinophilic intracytoplasmic inclusions, often arranged in short fascicles and whorls.
- Ancillary: The cells express vimentin, muscle actin in a peripheral 'tram-track' pattern, calponin, desmin, and CD99, with inclusions staining positive for calponin-1.
Reference Gallery:
Inclusion body fibromatosis. A single protuberant nodule with an erythematous surface on the lateral aspect of the distal fourth toe.
Inclusion body fibromatosis. Dome-shaped cellular dermal nodule composed of spindled cells arranged in short fascicles and whorls.
Inclusion body fibromatosis. Spindled cells surround dermal adnexa.
Inclusion body fibromatosis. Spindled cells directly beneath the epidermis, with fascicles growing perpendicular to the surface.
Inclusion body fibromatosis. High-power view demonstrates spindled cells with elongated, cytologically bland nuclei and rounded, eosinophilic paranuclear inclusions that often indent the nucleus.
Inclusion body fibromatosis. Gömöri trichrome stain highlights the intracytoplasmic inclusions (red).

Q: The pathognomonic histologic feature of Inclusion Body Fibromatosis is the presence of spindled cells containing rounded, eosinophilic [...] that frequently indent the nucleus.
Inclusion body fibromatosis. High-power view demonstrates spindled cells with elongated, cytologically bland nuclei and rounded, eosinophilic paranuclear inclusions that often indent the nucleus.
A: paranuclear inclusions
Back Extra: Inclusion Body Fibromatosis
- Clinical: Inclusion Body Fibromatosis typically presents as an asymptomatic, dome-shaped or polypoid cutaneous nodule on the hands or feet, especially the distal digits.
- Micro: Characterized by spindled cells with elongated, bland nuclei and eosinophilic intracytoplasmic inclusions, often arranged in short fascicles and whorls.
- Ancillary: The cells express vimentin, muscle actin in a peripheral 'tram-track' pattern, calponin, desmin, and CD99, with inclusions staining positive for calponin-1.
Reference Gallery:
Inclusion body fibromatosis. A single protuberant nodule with an erythematous surface on the lateral aspect of the distal fourth toe.
Inclusion body fibromatosis. Dome-shaped cellular dermal nodule composed of spindled cells arranged in short fascicles and whorls.
Inclusion body fibromatosis. Spindled cells surround dermal adnexa.
Inclusion body fibromatosis. Spindled cells directly beneath the epidermis, with fascicles growing perpendicular to the surface.
Inclusion body fibromatosis. High-power view demonstrates spindled cells with elongated, cytologically bland nuclei and rounded, eosinophilic paranuclear inclusions that often indent the nucleus.
Inclusion body fibromatosis. Gömöri trichrome stain highlights the intracytoplasmic inclusions (red).

Q: In Inclusion Body Fibromatosis, the characteristic intracytoplasmic inclusions can be highlighted in red using a [...] stain.
Inclusion body fibromatosis. Gömöri trichrome stain highlights the intracytoplasmic inclusions (red).
A: Gömöri trichrome
Back Extra: Inclusion Body Fibromatosis
- Clinical: Inclusion Body Fibromatosis typically presents as an asymptomatic, dome-shaped or polypoid cutaneous nodule on the hands or feet, especially the distal digits.
- Micro: Characterized by spindled cells with elongated, bland nuclei and eosinophilic intracytoplasmic inclusions, often arranged in short fascicles and whorls.
- Ancillary: The cells express vimentin, muscle actin in a peripheral 'tram-track' pattern, calponin, desmin, and CD99, with inclusions staining positive for calponin-1.
Reference Gallery:
Inclusion body fibromatosis. A single protuberant nodule with an erythematous surface on the lateral aspect of the distal fourth toe.
Inclusion body fibromatosis. Dome-shaped cellular dermal nodule composed of spindled cells arranged in short fascicles and whorls.
Inclusion body fibromatosis. Spindled cells surround dermal adnexa.
Inclusion body fibromatosis. Spindled cells directly beneath the epidermis, with fascicles growing perpendicular to the surface.
Inclusion body fibromatosis. High-power view demonstrates spindled cells with elongated, cytologically bland nuclei and rounded, eosinophilic paranuclear inclusions that often indent the nucleus.
Inclusion body fibromatosis. Gömöri trichrome stain highlights the intracytoplasmic inclusions (red).

Q: Microscopically, a Gardner Fibroma is composed of bland spindle cells and dense, thickened collagen characteristically interspersed with [...].
Gardner fibroma. Dense collagen with clefts and cracks and bland spindle cells.
A: clefts and cracks
Back Extra: Gardner Fibroma
- Clinical: Gardner fibromas are typically solitary, most common in children (especially boys), and often associated with familial adenomatous polyposis (FAP) and desmoid-type fibromatosis.
- Micro: These tumours are composed of dense collagen with clefts and cracks and bland spindle cells. Entrapped fat and mast cells can be seen, and the cut surface may show yellow, soft areas.
- Ancillary: Immunohistochemistry shows β-catenin positivity with nuclear accumulation, and CD34 is positive, while SMA is negative. Germline mutations in APC are common in FAP-associated tumours.
Reference Gallery:
Gardner fibroma. Dense collagen with clefts and cracks and bland spindle cells.

Q: A Gardner Fibroma is a soft tissue tumor (histology shown) that frequently occurs in children and often serves as a sentinel lesion for an underlying genetic syndrome known as [...].
Gardner fibroma. Dense collagen with clefts and cracks and bland spindle cells.
A: familial adenomatous polyposis (FAP)
Back Extra: Gardner Fibroma
- Clinical: Gardner fibromas are typically solitary, most common in children (especially boys), and often associated with familial adenomatous polyposis (FAP) and desmoid-type fibromatosis.
- Micro: These tumours are composed of dense collagen with clefts and cracks and bland spindle cells. Entrapped fat and mast cells can be seen, and the cut surface may show yellow, soft areas.
- Ancillary: Immunohistochemistry shows β-catenin positivity with nuclear accumulation, and CD34 is positive, while SMA is negative. Germline mutations in APC are common in FAP-associated tumours.
Reference Gallery:
Gardner fibroma. Dense collagen with clefts and cracks and bland spindle cells.

Q: Histologically, Multinucleate Cell Angiohistiocytoma features mildly increased telangiectatic blood vessels and distinctive multinucleated cells that are typically [...] with elongated cytoplasmic extensions.
Multinucleate cell angiohistiocytoma. Odd-shaped, angulated multinucleate cells with abundant long cytoplasmic extensions populate the dermis. Blood vessels are telangiectatic, with slightly hyalinized wall and prominent endothelial cells.
A: angulated and stellate
Back Extra: Multinucleate Cell Angiohistiocytoma
- Clinical: Multinucleate cell angiohistiocytoma presents as solitary or multiple smooth erythematous papules and nodules, typically affecting the dorsal hands, fingers, lower extremities, and trunk.
- Micro: The lesion consists of multinucleated cells that are angulated and stellate, with elongated cytoplasmic extensions, and increased numbers of small-calibre vessels with prominent endothelial cells.
- Ancillary: Multinucleated cells may express CD68 and factor XIIIa, but are generally negative for CD163, CD34, and factor VIII.
Reference Gallery:
Multinucleate cell angiohistiocytoma. Odd-shaped, angulated multinucleate cells with abundant long cytoplasmic extensions populate the dermis. Blood vessels are telangiectatic, with slightly hyalinized wall and prominent endothelial cells.
Multinucleate cell angiohistiocytoma. Superficial papillary and reticular dermal vessels, which are mildly increased in number, are telangiectatic with stromal fibrosis parallel to the epidermis.

Q: In Multinucleate Cell Angiohistiocytoma, the superficial papillary and reticular dermal vessels are telangiectatic and accompanied by stromal fibrosis that is oriented [...] to the epidermis.
Multinucleate cell angiohistiocytoma. Superficial papillary and reticular dermal vessels, which are mildly increased in number, are telangiectatic with stromal fibrosis parallel to the epidermis.
A: parallel
Back Extra: Multinucleate Cell Angiohistiocytoma
- Clinical: Multinucleate cell angiohistiocytoma presents as solitary or multiple smooth erythematous papules and nodules, typically affecting the dorsal hands, fingers, lower extremities, and trunk.
- Micro: The lesion consists of multinucleated cells that are angulated and stellate, with elongated cytoplasmic extensions, and increased numbers of small-calibre vessels with prominent endothelial cells.
- Ancillary: Multinucleated cells may express CD68 and factor XIIIa, but are generally negative for CD163, CD34, and factor VIII.
Reference Gallery:
Multinucleate cell angiohistiocytoma. Odd-shaped, angulated multinucleate cells with abundant long cytoplasmic extensions populate the dermis. Blood vessels are telangiectatic, with slightly hyalinized wall and prominent endothelial cells.
Multinucleate cell angiohistiocytoma. Superficial papillary and reticular dermal vessels, which are mildly increased in number, are telangiectatic with stromal fibrosis parallel to the epidermis.

Q: A classic histologic hallmark of Myofibroma and Myofibromatosis is the presence of myointimal-like nodular proliferations, commonly referred to as [...].
Myofibroma. An example showing almost exclusively myxohyaline myointimal vascular balls, with little intervening cellular primitive myoid stroma.
Myofibroma. Transition from vascular balls (midfield) to more cellular primitive myoid stroma (right).
A: vascular balls
Back Extra: Myofibroma and Myofibromatosis
- Clinical: Myofibroma can present as solitary, multicentric, or generalized forms. The solitary form is more common in males, while the multicentric form predominantly affects females.
- Micro: Characterized by a biphasic growth with alternating bundles of primitive, small rounded cells and plump spindled mesenchymal cells, along with myointimal-like nodular proliferations (vascular balls).
- Ancillary: Germline PDGFRB mutations predispose to myofibromatosis in affected families, while sporadic lesions have frequent somatic PDGFRB mutations.
Reference Gallery:
Myofibroma. A cellular myofibroma showing moderate to high cellularity (upper left) blending with hyalinized foci (lower right) within vascularized stroma containing thin-walled vessels.
Myofibroma. An example showing almost exclusively myxohyaline myointimal vascular balls, with little intervening cellular primitive myoid stroma.
Myofibroma. Transition from vascular balls (midfield) to more cellular primitive myoid stroma (right).
Myofibroma. An example with prominent vascular balls (upper field) abutting cellular primitive myoid stroma with pericytoma-like vessels (lower field).

Q: Microscopically, Myofibroma and Myofibromatosis exhibits a characteristic [...] growth pattern consisting of alternating bundles of primitive, small rounded cells and plump spindled mesenchymal cells.
Myofibroma. A cellular myofibroma showing moderate to high cellularity (upper left) blending with hyalinized foci (lower right) within vascularized stroma containing thin-walled vessels.
Myofibroma. Transition from vascular balls (midfield) to more cellular primitive myoid stroma (right).
A: biphasic
Back Extra: Myofibroma and Myofibromatosis
- Clinical: Myofibroma can present as solitary, multicentric, or generalized forms. The solitary form is more common in males, while the multicentric form predominantly affects females.
- Micro: Characterized by a biphasic growth with alternating bundles of primitive, small rounded cells and plump spindled mesenchymal cells, along with myointimal-like nodular proliferations (vascular balls).
- Ancillary: Germline PDGFRB mutations predispose to myofibromatosis in affected families, while sporadic lesions have frequent somatic PDGFRB mutations.
Reference Gallery:
Myofibroma. A cellular myofibroma showing moderate to high cellularity (upper left) blending with hyalinized foci (lower right) within vascularized stroma containing thin-walled vessels.
Myofibroma. An example showing almost exclusively myxohyaline myointimal vascular balls, with little intervening cellular primitive myoid stroma.
Myofibroma. Transition from vascular balls (midfield) to more cellular primitive myoid stroma (right).
Myofibroma. An example with prominent vascular balls (upper field) abutting cellular primitive myoid stroma with pericytoma-like vessels (lower field).

Q: In Myofibroma and Myofibromatosis, the cellular primitive myoid stroma frequently contains thin-walled, branching vascular channels described as [...]-like vessels.
Myofibroma. An example with prominent vascular balls (upper field) abutting cellular primitive myoid stroma with pericytoma-like vessels (lower field).
A: pericytoma
Back Extra: Myofibroma and Myofibromatosis
- Clinical: Myofibroma can present as solitary, multicentric, or generalized forms. The solitary form is more common in males, while the multicentric form predominantly affects females.
- Micro: Characterized by a biphasic growth with alternating bundles of primitive, small rounded cells and plump spindled mesenchymal cells, along with myointimal-like nodular proliferations (vascular balls).
- Ancillary: Germline PDGFRB mutations predispose to myofibromatosis in affected families, while sporadic lesions have frequent somatic PDGFRB mutations.
Reference Gallery:
Myofibroma. A cellular myofibroma showing moderate to high cellularity (upper left) blending with hyalinized foci (lower right) within vascularized stroma containing thin-walled vessels.
Myofibroma. An example showing almost exclusively myxohyaline myointimal vascular balls, with little intervening cellular primitive myoid stroma.
Myofibroma. Transition from vascular balls (midfield) to more cellular primitive myoid stroma (right).
Myofibroma. An example with prominent vascular balls (upper field) abutting cellular primitive myoid stroma with pericytoma-like vessels (lower field).

Q: The classic histologic hallmark of low-grade Myxofibrosarcoma is a hypocellular myxoid stroma containing mildly atypical spindle-to-stellate cells and prominent, elongated, [...] blood vessels.
Myxofibrosarcoma, low grade. A hypocellular myxoid neoplasm with mildly atypical, spindle-to-stellate cells with nuclear hyperchromasia and elongated, curvilinear blood vessels.
A: curvilinear
Back Extra: Myxofibrosarcoma
- Clinical: Myxofibrosarcoma is a slow-growing, often painless tumor that primarily affects the extremities, especially the thigh, and is more common in elderly patients.
- Micro: Low-grade myxofibrosarcoma is characterized by a hypocellular, myxoid stroma with mildly atypical spindle-to-stellate cells and elongated, curvilinear blood vessels.
- Ancillary: Myxofibrosarcomas often exhibit chromosomal rearrangements and copy-number alterations, particularly involving oncogenes on 5p, and commonly show mutations in TP53, RB1, and CDKN2A/CDKN2B.
Reference Gallery:
Subcutaneous myxofibrosarcoma. Superficially located myxofibrosarcoma with a multinodular growth pattern and a gelatinous, myxoid cut surface.
Myxofibrosarcoma, low grade. A hypocellular myxoid neoplasm with mildly atypical, spindle-to-stellate cells with nuclear hyperchromasia and elongated, curvilinear blood vessels.
Dermal myxofibrosarcoma. A typical dermal myxofibrosarcoma with infiltrative, multinodular growth.
Subcutaneous myxofibrosarcoma. A myxofibrosarcoma extensively infiltrating the subcutaneous adipose tissue.
Myxofibrosarcoma, intermediate grade. More cellular and atypical cells and occasional mucin-engulfing pseudolipoblasts surround long curvilinear vessels in myxoid stroma.
Myxofibrosarcoma, high grade. A high-grade solid component resembling undifferentiated pleomorphic sarcoma (left) is juxtaposed to an area with typical histology of myxofibrosarcoma (right). Bizarre giant cells with storiform arrangement are frequent.
Epithelioid myxofibrosarcoma, high grade. An abrupt transition from the low-grade area (right lower) to a high-grade epithelioid component (left upper) presenting cohesive clusters or even confluent sheets.
Epithelioid myxofibrosarcoma, high grade. Note the enlarged epithelioid cells with abundant eosinophilic cytoplasm, prominent nucleoli, and atypical mitoses.

Q: Grossly, superficially located Myxofibrosarcoma often demonstrates a multinodular growth pattern with a characteristic [...] cut surface, reflecting its underlying myxoid composition.
Subcutaneous myxofibrosarcoma. Superficially located myxofibrosarcoma with a multinodular growth pattern and a gelatinous, myxoid cut surface.
A: gelatinous
Back Extra: Myxofibrosarcoma
- Clinical: Myxofibrosarcoma is a slow-growing, often painless tumor that primarily affects the extremities, especially the thigh, and is more common in elderly patients.
- Micro: Low-grade myxofibrosarcoma is characterized by a hypocellular, myxoid stroma with mildly atypical spindle-to-stellate cells and elongated, curvilinear blood vessels.
- Ancillary: Myxofibrosarcomas often exhibit chromosomal rearrangements and copy-number alterations, particularly involving oncogenes on 5p, and commonly show mutations in TP53, RB1, and CDKN2A/CDKN2B.
Reference Gallery:
Subcutaneous myxofibrosarcoma. Superficially located myxofibrosarcoma with a multinodular growth pattern and a gelatinous, myxoid cut surface.
Myxofibrosarcoma, low grade. A hypocellular myxoid neoplasm with mildly atypical, spindle-to-stellate cells with nuclear hyperchromasia and elongated, curvilinear blood vessels.
Dermal myxofibrosarcoma. A typical dermal myxofibrosarcoma with infiltrative, multinodular growth.
Subcutaneous myxofibrosarcoma. A myxofibrosarcoma extensively infiltrating the subcutaneous adipose tissue.
Myxofibrosarcoma, intermediate grade. More cellular and atypical cells and occasional mucin-engulfing pseudolipoblasts surround long curvilinear vessels in myxoid stroma.
Myxofibrosarcoma, high grade. A high-grade solid component resembling undifferentiated pleomorphic sarcoma (left) is juxtaposed to an area with typical histology of myxofibrosarcoma (right). Bizarre giant cells with storiform arrangement are frequent.
Epithelioid myxofibrosarcoma, high grade. An abrupt transition from the low-grade area (right lower) to a high-grade epithelioid component (left upper) presenting cohesive clusters or even confluent sheets.
Epithelioid myxofibrosarcoma, high grade. Note the enlarged epithelioid cells with abundant eosinophilic cytoplasm, prominent nucleoli, and atypical mitoses.

Q: As Myxofibrosarcoma progresses to a high-grade tumor, it often develops solid cellular components resembling [...] (UPS) with frequent bizarre giant cells.
Myxofibrosarcoma, high grade. A high-grade solid component resembling undifferentiated pleomorphic sarcoma (left) is juxtaposed to an area with typical histology of myxofibrosarcoma (right). Bizarre giant cells with storiform arrangement are frequent.
A: undifferentiated pleomorphic sarcoma
Back Extra: Myxofibrosarcoma
- Clinical: Myxofibrosarcoma is a slow-growing, often painless tumor that primarily affects the extremities, especially the thigh, and is more common in elderly patients.
- Micro: Low-grade myxofibrosarcoma is characterized by a hypocellular, myxoid stroma with mildly atypical spindle-to-stellate cells and elongated, curvilinear blood vessels.
- Ancillary: Myxofibrosarcomas often exhibit chromosomal rearrangements and copy-number alterations, particularly involving oncogenes on 5p, and commonly show mutations in TP53, RB1, and CDKN2A/CDKN2B.
Reference Gallery:
Subcutaneous myxofibrosarcoma. Superficially located myxofibrosarcoma with a multinodular growth pattern and a gelatinous, myxoid cut surface.
Myxofibrosarcoma, low grade. A hypocellular myxoid neoplasm with mildly atypical, spindle-to-stellate cells with nuclear hyperchromasia and elongated, curvilinear blood vessels.
Dermal myxofibrosarcoma. A typical dermal myxofibrosarcoma with infiltrative, multinodular growth.
Subcutaneous myxofibrosarcoma. A myxofibrosarcoma extensively infiltrating the subcutaneous adipose tissue.
Myxofibrosarcoma, intermediate grade. More cellular and atypical cells and occasional mucin-engulfing pseudolipoblasts surround long curvilinear vessels in myxoid stroma.
Myxofibrosarcoma, high grade. A high-grade solid component resembling undifferentiated pleomorphic sarcoma (left) is juxtaposed to an area with typical histology of myxofibrosarcoma (right). Bizarre giant cells with storiform arrangement are frequent.
Epithelioid myxofibrosarcoma, high grade. An abrupt transition from the low-grade area (right lower) to a high-grade epithelioid component (left upper) presenting cohesive clusters or even confluent sheets.
Epithelioid myxofibrosarcoma, high grade. Note the enlarged epithelioid cells with abundant eosinophilic cytoplasm, prominent nucleoli, and atypical mitoses.

Q: Microscopically, Myxoinflammatory Fibroblastic Sarcoma is characterized by prominent inflammation, multivacuolated pseudolipoblasts, and binucleated tumor cells with inclusion-like macronucleoli that closely mimic [...] cells.
Myxoinflammatory fibroblastic sarcoma. Binucleated tumour cells with inclusion-like macronucleoli may closely mimic Reed–Sternberg cells.
Myxoinflammatory fibroblastic sarcoma. High-power view of pseudolipoblasts (multivacuolated cells containing mucin).
A: Reed-Sternberg
Back Extra: Myxoinflammatory Fibroblastic Sarcoma
- Clinical: Myxoinflammatory fibroblastic sarcoma typically manifests as a painless mass in the acral regions, particularly the hands and feet, and often mimics infection or other inflammatory conditions.
- Micro: The tumour is characterized by a myxohyaline stroma with dense inflammation, pleomorphic fibroblastic cells, and prominent macronucleoli. Pseudolipoblasts and bizarre cells are also common.
- Ancillary: Cytogenetic studies show amplification of the VGLL3 gene and a t(1;10) translocation in a significant proportion of cases.
Reference Gallery:
Myxoinflammatory fibroblastic sarcoma. This tumour type shows infiltrative margins and is often dominated by chronic inflammation, thereby mimicking an inflammatory process. Note the areas with prominent myxoid stroma.
Myxoinflammatory fibroblastic sarcoma. In the myxoid areas, pseudolipoblasts (multivacuolated cells containing mucin) may be prominent.
Myxoinflammatory fibroblastic sarcoma. The tumour cells contain vesicular chromatin and large nucleoli. Note the scattered mixed inflammatory cells.
Myxoinflammatory fibroblastic sarcoma. Binucleated tumour cells with inclusion-like macronucleoli may closely mimic Reed–Sternberg cells.
Myxoinflammatory fibroblastic sarcoma. Alcian blue staining the myxoid stroma of the tumour.
Myxoinflammatory fibroblastic sarcoma. High-power view of pseudolipoblasts (multivacuolated cells containing mucin).
Myxoinflammatory fibroblastic sarcoma. Array comparative genomic hybridization profile of a myxoinflammatory fibroblastic sarcoma showing amplification of the VGLL3 gene (arrow) and unbalanced t(1;10) with breakpoints in the OGA gene (10q24) and near the TGFBR3 gene (1p22) (arrowheads).

Q: Molecular studies in Myxoinflammatory Fibroblastic Sarcoma frequently reveal an unbalanced t(1;10) translocation alongside characteristic amplification of the [...] gene.
Myxoinflammatory fibroblastic sarcoma. Array comparative genomic hybridization profile of a myxoinflammatory fibroblastic sarcoma showing amplification of the VGLL3 gene (arrow) and unbalanced t(1;10) with breakpoints in the OGA gene (10q24) and near the TGFBR3 gene (1p22) (arrowheads).
A: VGLL3
Back Extra: Myxoinflammatory Fibroblastic Sarcoma
- Clinical: Myxoinflammatory fibroblastic sarcoma typically manifests as a painless mass in the acral regions, particularly the hands and feet, and often mimics infection or other inflammatory conditions.
- Micro: The tumour is characterized by a myxohyaline stroma with dense inflammation, pleomorphic fibroblastic cells, and prominent macronucleoli. Pseudolipoblasts and bizarre cells are also common.
- Ancillary: Cytogenetic studies show amplification of the VGLL3 gene and a t(1;10) translocation in a significant proportion of cases.
Reference Gallery:
Myxoinflammatory fibroblastic sarcoma. This tumour type shows infiltrative margins and is often dominated by chronic inflammation, thereby mimicking an inflammatory process. Note the areas with prominent myxoid stroma.
Myxoinflammatory fibroblastic sarcoma. In the myxoid areas, pseudolipoblasts (multivacuolated cells containing mucin) may be prominent.
Myxoinflammatory fibroblastic sarcoma. The tumour cells contain vesicular chromatin and large nucleoli. Note the scattered mixed inflammatory cells.
Myxoinflammatory fibroblastic sarcoma. Binucleated tumour cells with inclusion-like macronucleoli may closely mimic Reed–Sternberg cells.
Myxoinflammatory fibroblastic sarcoma. Alcian blue staining the myxoid stroma of the tumour.
Myxoinflammatory fibroblastic sarcoma. High-power view of pseudolipoblasts (multivacuolated cells containing mucin).
Myxoinflammatory fibroblastic sarcoma. Array comparative genomic hybridization profile of a myxoinflammatory fibroblastic sarcoma showing amplification of the VGLL3 gene (arrow) and unbalanced t(1;10) with breakpoints in the OGA gene (10q24) and near the TGFBR3 gene (1p22) (arrowheads).

Q: The prominent myxoid stroma in Myxoinflammatory Fibroblastic Sarcoma contains abundant mucin, which can be highlighted using an [...] stain.
Myxoinflammatory fibroblastic sarcoma. Alcian blue staining the myxoid stroma of the tumour.
A: Alcian blue
Back Extra: Myxoinflammatory Fibroblastic Sarcoma
- Clinical: Myxoinflammatory fibroblastic sarcoma typically manifests as a painless mass in the acral regions, particularly the hands and feet, and often mimics infection or other inflammatory conditions.
- Micro: The tumour is characterized by a myxohyaline stroma with dense inflammation, pleomorphic fibroblastic cells, and prominent macronucleoli. Pseudolipoblasts and bizarre cells are also common.
- Ancillary: Cytogenetic studies show amplification of the VGLL3 gene and a t(1;10) translocation in a significant proportion of cases.
Reference Gallery:
Myxoinflammatory fibroblastic sarcoma. This tumour type shows infiltrative margins and is often dominated by chronic inflammation, thereby mimicking an inflammatory process. Note the areas with prominent myxoid stroma.
Myxoinflammatory fibroblastic sarcoma. In the myxoid areas, pseudolipoblasts (multivacuolated cells containing mucin) may be prominent.
Myxoinflammatory fibroblastic sarcoma. The tumour cells contain vesicular chromatin and large nucleoli. Note the scattered mixed inflammatory cells.
Myxoinflammatory fibroblastic sarcoma. Binucleated tumour cells with inclusion-like macronucleoli may closely mimic Reed–Sternberg cells.
Myxoinflammatory fibroblastic sarcoma. Alcian blue staining the myxoid stroma of the tumour.
Myxoinflammatory fibroblastic sarcoma. High-power view of pseudolipoblasts (multivacuolated cells containing mucin).
Myxoinflammatory fibroblastic sarcoma. Array comparative genomic hybridization profile of a myxoinflammatory fibroblastic sarcoma showing amplification of the VGLL3 gene (arrow) and unbalanced t(1;10) with breakpoints in the OGA gene (10q24) and near the TGFBR3 gene (1p22) (arrowheads).

Q: Histologically, Nodular Fasciitis characteristically features plump myofibroblastic spindle cells arranged in a loose, [...]-like growth pattern with prominent myxoid stroma and extravasated red blood cells.
Nodular fasciitis. Myofibroblastic spindle cells with tissue culture growth pattern, myxoid stroma, and extravasated red blood cells are characteristic.
A: tissue culture
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis presents as a rapidly growing subcutaneous mass, typically in the forearm, thigh, or upper arm, and can spontaneously regress.
- Micro: Myofibroblastic spindle cells with a tissue culture-like growth pattern, myxoid stroma, and extravasated red blood cells are characteristic features.
- Ancillary: Nodular fasciitis harbors USP6 rearrangements, most commonly the MYH9::USP6 fusion, which is seen in about 90% of cases.
Reference Gallery:
Nodular fasciitis. A nodular subcutaneous mass, which can sometimes involve the overlying dermis.
Nodular fasciitis. Myofibroblastic spindle cells with tissue culture growth pattern, myxoid stroma, and extravasated red blood cells are characteristic.
Nodular fasciitis. Scattered multinucleated giant cells and inflammatory cells can be seen.
Nodular fasciitis. Some tumours may have keloidal-like collagen bundles.
Nodular fasciitis. Schematic representation of the MYH9::USP6 fusion.

Q: The vast majority of Nodular Fasciitis cases are now known to be neoplastic and harbor a recurrent gene rearrangement, most commonly the [USP6] fusion.
Nodular fasciitis. Schematic representation of the MYH9::USP6 fusion.
A: MYH9
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis presents as a rapidly growing subcutaneous mass, typically in the forearm, thigh, or upper arm, and can spontaneously regress.
- Micro: Myofibroblastic spindle cells with a tissue culture-like growth pattern, myxoid stroma, and extravasated red blood cells are characteristic features.
- Ancillary: Nodular fasciitis harbors USP6 rearrangements, most commonly the MYH9::USP6 fusion, which is seen in about 90% of cases.
Reference Gallery:
Nodular fasciitis. A nodular subcutaneous mass, which can sometimes involve the overlying dermis.
Nodular fasciitis. Myofibroblastic spindle cells with tissue culture growth pattern, myxoid stroma, and extravasated red blood cells are characteristic.
Nodular fasciitis. Scattered multinucleated giant cells and inflammatory cells can be seen.
Nodular fasciitis. Some tumours may have keloidal-like collagen bundles.
Nodular fasciitis. Schematic representation of the MYH9::USP6 fusion.

Q: While classic Nodular Fasciitis features myxoid stroma and inflammatory cells, some tumors (particularly older lesions) can become more fibrotic and display thick, [...]-like collagen bundles.
Nodular fasciitis. Some tumours may have keloidal-like collagen bundles.
A: keloidal
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis presents as a rapidly growing subcutaneous mass, typically in the forearm, thigh, or upper arm, and can spontaneously regress.
- Micro: Myofibroblastic spindle cells with a tissue culture-like growth pattern, myxoid stroma, and extravasated red blood cells are characteristic features.
- Ancillary: Nodular fasciitis harbors USP6 rearrangements, most commonly the MYH9::USP6 fusion, which is seen in about 90% of cases.
Reference Gallery:
Nodular fasciitis. A nodular subcutaneous mass, which can sometimes involve the overlying dermis.
Nodular fasciitis. Myofibroblastic spindle cells with tissue culture growth pattern, myxoid stroma, and extravasated red blood cells are characteristic.
Nodular fasciitis. Scattered multinucleated giant cells and inflammatory cells can be seen.
Nodular fasciitis. Some tumours may have keloidal-like collagen bundles.
Nodular fasciitis. Schematic representation of the MYH9::USP6 fusion.

Q: A solitary, painless soft tissue tumor arising in the posterior neck, characterized microscopically by bland fibroblasts, thick collagen fibers, and entrapped fat or skeletal muscle, is classic for [...].
Nuchal-type fibroma. Thickened collagen fibres and small fibroblasts with entrapped fat.
Nuchal-type fibroma. The lesional cells are bland spindled fibroblasts. Extension into skeletal muscle is common.
A: Nuchal-Type Fibroma
Back Extra: Nuchal-Type Fibroma
- Clinical: Patients typically present with a solitary, painless swelling in the posterior neck, with a male predilection and peak incidence between the third and fifth decades of life.
- Micro: Nuchal-type fibromas are hypocellular tumours with small fibroblasts, thick collagen fibres, and often entrapped fat, skeletal muscle, and nerves.
- Ancillary: Immunohistochemistry shows negative staining for desmin, actin, S100, and EMA, with possible nuclear expression of β-catenin.
Reference Gallery:
Nuchal-type fibroma. Thickened collagen fibres and small fibroblasts with entrapped fat.
Nuchal-type fibroma. The lesional cells are bland spindled fibroblasts. Extension into skeletal muscle is common.

Q: Microscopically, Nuchal-Type Fibroma is a hypocellular tumor featuring thick collagen fibers and bland spindled fibroblasts that characteristically entrap adjacent normal structures, particularly [...].
Nuchal-type fibroma. Thickened collagen fibres and small fibroblasts with entrapped fat.
Nuchal-type fibroma. The lesional cells are bland spindled fibroblasts. Extension into skeletal muscle is common.
A: adipose tissue and skeletal muscle
Back Extra: Nuchal-Type Fibroma
- Clinical: Patients typically present with a solitary, painless swelling in the posterior neck, with a male predilection and peak incidence between the third and fifth decades of life.
- Micro: Nuchal-type fibromas are hypocellular tumours with small fibroblasts, thick collagen fibres, and often entrapped fat, skeletal muscle, and nerves.
- Ancillary: Immunohistochemistry shows negative staining for desmin, actin, S100, and EMA, with possible nuclear expression of β-catenin.
Reference Gallery:
Nuchal-type fibroma. Thickened collagen fibres and small fibroblasts with entrapped fat.
Nuchal-type fibroma. The lesional cells are bland spindled fibroblasts. Extension into skeletal muscle is common.

Q: The diagnosis of [...] should be strongly suspected in a young patient presenting with a solitary, flat, circumscribed tumor on the neck that microscopically exhibits a characteristic dermal zonation pattern of spindle cells.
Plaque-like CD34-positive dermal fibroma. A flat, slightly indurated circumscribed tumour on the anterior aspect of the neck of a young boy.
Plaque-like CD34-positive dermal fibroma. Characteristic zonation of tumour cells, with perpendicular arrangement in the upper portion and horizontal arrangement in the deeper part.
A: Plaque-like CD34-positive dermal fibroma
Back Extra: Plaque-like CD34-positive dermal fibroma
- Clinical: Plaque-like CD34-positive dermal fibroma typically presents as a solitary, slowly growing, well-demarcated, erythematous to brown-yellow plaque, often on the neck or trunk of children and young adults.
- Micro: The tumour is characterized by a band-like proliferation of bland CD34-positive spindle cells in the upper and mid dermis, with a characteristic zonation pattern and sparing of the papillary dermis.
- Ancillary: Tumour cells are diffusely positive for CD34 and fascin, with inconsistent staining for factor XIIIa.
Reference Gallery:
Plaque-like CD34-positive dermal fibroma. A flat, slightly indurated circumscribed tumour on the anterior aspect of the neck of a young boy.
Plaque-like CD34-positive dermal fibroma. Characteristic zonation of tumour cells, with perpendicular arrangement in the upper portion and horizontal arrangement in the deeper part.
Plaque-like CD34-positive dermal fibroma. CD34 staining reveals the characteristic fingerprint pattern of a fibroblastic tumour.

Q: Histologically, Plaque-like CD34-positive dermal fibroma features a band-like proliferation of bland spindle cells with a characteristic [...] pattern, demonstrating a perpendicular arrangement in the upper portion and a horizontal arrangement deeper in the dermis.
Plaque-like CD34-positive dermal fibroma. Characteristic zonation of tumour cells, with perpendicular arrangement in the upper portion and horizontal arrangement in the deeper part.
A: zonation
Back Extra: Plaque-like CD34-positive dermal fibroma
- Clinical: Plaque-like CD34-positive dermal fibroma typically presents as a solitary, slowly growing, well-demarcated, erythematous to brown-yellow plaque, often on the neck or trunk of children and young adults.
- Micro: The tumour is characterized by a band-like proliferation of bland CD34-positive spindle cells in the upper and mid dermis, with a characteristic zonation pattern and sparing of the papillary dermis.
- Ancillary: Tumour cells are diffusely positive for CD34 and fascin, with inconsistent staining for factor XIIIa.
Reference Gallery:
Plaque-like CD34-positive dermal fibroma. A flat, slightly indurated circumscribed tumour on the anterior aspect of the neck of a young boy.
Plaque-like CD34-positive dermal fibroma. Characteristic zonation of tumour cells, with perpendicular arrangement in the upper portion and horizontal arrangement in the deeper part.
Plaque-like CD34-positive dermal fibroma. CD34 staining reveals the characteristic fingerprint pattern of a fibroblastic tumour.

Q: In Plaque-like CD34-positive dermal fibroma, immunohistochemical staining for CD34 characteristically reveals a distinct [...] pattern of the fibroblastic tumor cells.
Plaque-like CD34-positive dermal fibroma. CD34 staining reveals the characteristic fingerprint pattern of a fibroblastic tumour.
A: fingerprint
Back Extra: Plaque-like CD34-positive dermal fibroma
- Clinical: Plaque-like CD34-positive dermal fibroma typically presents as a solitary, slowly growing, well-demarcated, erythematous to brown-yellow plaque, often on the neck or trunk of children and young adults.
- Micro: The tumour is characterized by a band-like proliferation of bland CD34-positive spindle cells in the upper and mid dermis, with a characteristic zonation pattern and sparing of the papillary dermis.
- Ancillary: Tumour cells are diffusely positive for CD34 and fascin, with inconsistent staining for factor XIIIa.
Reference Gallery:
Plaque-like CD34-positive dermal fibroma. A flat, slightly indurated circumscribed tumour on the anterior aspect of the neck of a young boy.
Plaque-like CD34-positive dermal fibroma. Characteristic zonation of tumour cells, with perpendicular arrangement in the upper portion and horizontal arrangement in the deeper part.
Plaque-like CD34-positive dermal fibroma. CD34 staining reveals the characteristic fingerprint pattern of a fibroblastic tumour.

Q: A rapidly growing, ulcerated nodule on the sun-damaged skin of an elderly patient reveals marked nuclear atypia, multinucleated tumor giant cells, and negative staining for S100 and cytokeratins. This presentation is diagnostic of [...].
Pleomorphic dermal sarcoma. Tumour cells are epithelioid and spindled, showing marked nuclear atypia; multinucleated tumour giant cells are admixed.
A: Pleomorphic Dermal Sarcoma
Back Extra: Pleomorphic Dermal Sarcoma
- Clinical: Pleomorphic dermal sarcoma typically presents as a rapidly growing nodule with a diameter of 5–50 mm, often ulcerated, in elderly, sun-damaged skin of White patients.
- Micro: The tumour is characterized by pleomorphic spindle and epithelioid cells with marked nuclear atypia, multinucleated giant cells, brisk mitotic activity, and focal necrosis.
- Ancillary: Immunohistochemical studies show negative staining for S100, desmin, and cytokeratins, with positive staining for CD10, CD99, and PDGFRB. High mutation load with UV radiation signature is common.
Reference Gallery:
Pleomorphic dermal sarcoma. This large and cellular tumour is based within dermis and extends to the overlying epidermis.
Pleomorphic dermal sarcoma. Tumour cells are epithelioid and spindled, showing marked nuclear atypia; multinucleated tumour giant cells are admixed.
Pleomorphic dermal sarcoma. This tumour is characterized by infiltrative growth, with invasion of subcutaneous adipose tissue and the underlying galea.
Pleomorphic dermal sarcoma. There is focal necrosis on the right.

Q: Histologically, Pleomorphic Dermal Sarcoma is distinguished from atypical fibroxanthoma by deep tissue invasion or the presence of focal [...].
Pleomorphic dermal sarcoma. There is focal necrosis on the right.
A: necrosis
Back Extra: Pleomorphic Dermal Sarcoma
- Clinical: Pleomorphic dermal sarcoma typically presents as a rapidly growing nodule with a diameter of 5–50 mm, often ulcerated, in elderly, sun-damaged skin of White patients.
- Micro: The tumour is characterized by pleomorphic spindle and epithelioid cells with marked nuclear atypia, multinucleated giant cells, brisk mitotic activity, and focal necrosis.
- Ancillary: Immunohistochemical studies show negative staining for S100, desmin, and cytokeratins, with positive staining for CD10, CD99, and PDGFRB. High mutation load with UV radiation signature is common.
Reference Gallery:
Pleomorphic dermal sarcoma. This large and cellular tumour is based within dermis and extends to the overlying epidermis.
Pleomorphic dermal sarcoma. Tumour cells are epithelioid and spindled, showing marked nuclear atypia; multinucleated tumour giant cells are admixed.
Pleomorphic dermal sarcoma. This tumour is characterized by infiltrative growth, with invasion of subcutaneous adipose tissue and the underlying galea.
Pleomorphic dermal sarcoma. There is focal necrosis on the right.

Q: In Pleomorphic Dermal Sarcoma, the tumor demonstrates an infiltrative growth pattern that frequently extends deep to involve the underlying galea or [...].
Pleomorphic dermal sarcoma. This tumour is characterized by infiltrative growth, with invasion of subcutaneous adipose tissue and the underlying galea.
A: subcutaneous adipose tissue
Back Extra: Pleomorphic Dermal Sarcoma
- Clinical: Pleomorphic dermal sarcoma typically presents as a rapidly growing nodule with a diameter of 5–50 mm, often ulcerated, in elderly, sun-damaged skin of White patients.
- Micro: The tumour is characterized by pleomorphic spindle and epithelioid cells with marked nuclear atypia, multinucleated giant cells, brisk mitotic activity, and focal necrosis.
- Ancillary: Immunohistochemical studies show negative staining for S100, desmin, and cytokeratins, with positive staining for CD10, CD99, and PDGFRB. High mutation load with UV radiation signature is common.
Reference Gallery:
Pleomorphic dermal sarcoma. This large and cellular tumour is based within dermis and extends to the overlying epidermis.
Pleomorphic dermal sarcoma. Tumour cells are epithelioid and spindled, showing marked nuclear atypia; multinucleated tumour giant cells are admixed.
Pleomorphic dermal sarcoma. This tumour is characterized by infiltrative growth, with invasion of subcutaneous adipose tissue and the underlying galea.
Pleomorphic dermal sarcoma. There is focal necrosis on the right.

Q: Microscopically, Pleomorphic fibroma presents as a papule composed of dense collagen bundles admixed with stellate fibroblasts that characteristically exhibit striking [...] and hyperchromasia.
Pleomorphic fibroma. A dome-shaped papule with stellate hyperchromatic fibroblasts.
Pleomorphic fibroma. Collagen bundles admixed with atypical fibroblasts demonstrating degenerative nuclear pleomorphism and hyperchromasia.
A: degenerative nuclear pleomorphism
Back Extra: Pleomorphic fibroma
- Clinical: Pleomorphic fibromas are painless, single, slow-growing, fleshy polyps or papules, typically affecting the extremities, trunk, and head and neck in middle-aged adults.
- Micro: These tumors are hypocellular, composed of dense, haphazardly arranged collagen bundles admixed with spindle cells and large pleomorphic cells with hyperchromatic, multilobulated nuclei.
- Ancillary: Immunohistochemistry shows positivity for CD34 and loss of RB1 expression, with aberrant p53 expression in Li–Fraumeni syndrome–associated cases.
Reference Gallery:
Pleomorphic fibroma. A dome-shaped papule with stellate hyperchromatic fibroblasts.
Pleomorphic fibroma. Collagen bundles admixed with atypical fibroblasts demonstrating degenerative nuclear pleomorphism and hyperchromasia.

Q: A key histologic characteristic of Pleomorphic fibroma is that despite the presence of atypical, hyperchromatic, and multilobulated nuclei, the tumor remains markedly [...] overall.
Pleomorphic fibroma. A dome-shaped papule with stellate hyperchromatic fibroblasts.
Pleomorphic fibroma. Collagen bundles admixed with atypical fibroblasts demonstrating degenerative nuclear pleomorphism and hyperchromasia.
A: hypocellular
Back Extra: Pleomorphic fibroma
- Clinical: Pleomorphic fibromas are painless, single, slow-growing, fleshy polyps or papules, typically affecting the extremities, trunk, and head and neck in middle-aged adults.
- Micro: These tumors are hypocellular, composed of dense, haphazardly arranged collagen bundles admixed with spindle cells and large pleomorphic cells with hyperchromatic, multilobulated nuclei.
- Ancillary: Immunohistochemistry shows positivity for CD34 and loss of RB1 expression, with aberrant p53 expression in Li–Fraumeni syndrome–associated cases.
Reference Gallery:
Pleomorphic fibroma. A dome-shaped papule with stellate hyperchromatic fibroblasts.
Pleomorphic fibroma. Collagen bundles admixed with atypical fibroblasts demonstrating degenerative nuclear pleomorphism and hyperchromasia.

Q: As the name implies, a Plexiform Fibrohistiocytic Tumor typically demonstrates a deeply situated [...] growth pattern composed of small cellular nodules within the dermis and subcutaneous adipose tissue.
Plexiform fibrohistiocytic tumour. The tumour is located in dermis and subcutaneous adipose tissue and shows a plexiform growth composed of small cellular nodules.
A: plexiform
Back Extra: Plexiform Fibrohistiocytic Tumour
- Clinical: Plexiform fibrohistiocytic tumours are most commonly found in children, adolescents, and young adults, with a median age ranging from 14.5 to 20 years.
- Micro: The tumour shows a biphasic morphology characterized by small to medium-sized nodules of histiocyte-rich foci with osteoclast-like giant cells and fascicular spindled myofibroblastic fascicles.
- Ancillary: Expression of SMA in the spindled myofibroblastic foci and CD68 in the histiocytic cannonballs is typical, while CD34, desmin, EMA, keratin, and S100 are generally negative.
Reference Gallery:
Plexiform fibrohistiocytic tumour. The tumour is located in dermis and subcutaneous adipose tissue and shows a plexiform growth composed of small cellular nodules.
Plexiform fibrohistiocytic tumour. The small nodules are composed of bland and uniform histiocytoid cells with admixed osteoclast-like giant cells and haemorrhage.
Plexiform fibrohistiocytic tumour. A fascicular growth of uniform spindle cells may be an additional or the predominant finding in a subset of these tumours. Also note the mitotic figure (on the left side of the field).

Q: A characteristic histologic feature of Plexiform Fibrohistiocytic Tumor is its biphasic morphology, featuring spindled fascicles and small nodules rich in bland histiocytes and scattered [...].
Plexiform fibrohistiocytic tumour. The small nodules are composed of bland and uniform histiocytoid cells with admixed osteoclast-like giant cells and haemorrhage.
A: osteoclast-like giant cells
Back Extra: Plexiform Fibrohistiocytic Tumour
- Clinical: Plexiform fibrohistiocytic tumours are most commonly found in children, adolescents, and young adults, with a median age ranging from 14.5 to 20 years.
- Micro: The tumour shows a biphasic morphology characterized by small to medium-sized nodules of histiocyte-rich foci with osteoclast-like giant cells and fascicular spindled myofibroblastic fascicles.
- Ancillary: Expression of SMA in the spindled myofibroblastic foci and CD68 in the histiocytic cannonballs is typical, while CD34, desmin, EMA, keratin, and S100 are generally negative.
Reference Gallery:
Plexiform fibrohistiocytic tumour. The tumour is located in dermis and subcutaneous adipose tissue and shows a plexiform growth composed of small cellular nodules.
Plexiform fibrohistiocytic tumour. The small nodules are composed of bland and uniform histiocytoid cells with admixed osteoclast-like giant cells and haemorrhage.
Plexiform fibrohistiocytic tumour. A fascicular growth of uniform spindle cells may be an additional or the predominant finding in a subset of these tumours. Also note the mitotic figure (on the left side of the field).

Q: The biphasic morphology of a Plexiform Fibrohistiocytic Tumor includes histiocytoid nodules admixed with a distinct fascicular growth of uniform, spindled [...].
Plexiform fibrohistiocytic tumour. A fascicular growth of uniform spindle cells may be an additional or the predominant finding in a subset of these tumours. Also note the mitotic figure (on the left side of the field).
A: myofibroblasts
Back Extra: Plexiform Fibrohistiocytic Tumour
- Clinical: Plexiform fibrohistiocytic tumours are most commonly found in children, adolescents, and young adults, with a median age ranging from 14.5 to 20 years.
- Micro: The tumour shows a biphasic morphology characterized by small to medium-sized nodules of histiocyte-rich foci with osteoclast-like giant cells and fascicular spindled myofibroblastic fascicles.
- Ancillary: Expression of SMA in the spindled myofibroblastic foci and CD68 in the histiocytic cannonballs is typical, while CD34, desmin, EMA, keratin, and S100 are generally negative.
Reference Gallery:
Plexiform fibrohistiocytic tumour. The tumour is located in dermis and subcutaneous adipose tissue and shows a plexiform growth composed of small cellular nodules.
Plexiform fibrohistiocytic tumour. The small nodules are composed of bland and uniform histiocytoid cells with admixed osteoclast-like giant cells and haemorrhage.
Plexiform fibrohistiocytic tumour. A fascicular growth of uniform spindle cells may be an additional or the predominant finding in a subset of these tumours. Also note the mitotic figure (on the left side of the field).

Q: Histologically, Superficial Acral Fibromyxoma forms a lobulated proliferation of uniform spindle cells in a variably collagenous to [...] stroma, which can notably infiltrate the subcutis and underlying bone.
Superficial acral fibromyxoma. A lobular architecture is seen, with the tumour infiltrating into the subcutis and involving underlying bone.
Superficial acral fibromyxoma. A prominent myxoid stroma is observed.
Superficial acral fibromyxoma. There is a fascicular growth of uniform spindle cells in a fibromyxoid stroma. Note the absence of cytological atypia.
A: myxoid
Back Extra: Superficial Acral Fibromyxoma
- Clinical: Superficial acral fibromyxomas are slowly growing, often painful lesions that range in size from 10 to 50 mm, typically found on the periungual region of digits.
- Micro: These tumours are lobulated, with a hypocellular to cellular stroma, and a variably collagenous to myxoid appearance. They may show infiltrative borders and involvement of underlying bone.
- Ancillary: Tumour cells are positive for CD34, CD99, and nestin, and often show a loss of RB1 expression.
Reference Gallery:
Superficial acral fibromyxoma. A lobular architecture is seen, with the tumour infiltrating into the subcutis and involving underlying bone.
Superficial acral fibromyxoma. A prominent myxoid stroma is observed.
Superficial acral fibromyxoma. A tumour with more collagenous stroma and a vaguely fascicular growth pattern.
Superficial acral fibromyxoma. A tumour with a more storiform growth pattern and conspicuous vasculature.
Cellular acral fibromyxoma. Acral fibromyxoma with increased cellularity.
Superficial acral fibromyxoma. The tumour cells are positive for CD34.
Superficial acral fibromyxoma. There is a fascicular growth of uniform spindle cells in a fibromyxoid stroma. Note the absence of cytological atypia.
Superficial acral fibromyxoma. The tumour cells show a loss of RB1 expression.

Q: The uniform spindle cells of Superficial Acral Fibromyxoma characteristically show strong immunohistochemical positivity for [...], as well as CD99 and nestin.
Superficial acral fibromyxoma. The tumour cells are positive for CD34.
A: CD34
Back Extra: Superficial Acral Fibromyxoma
- Clinical: Superficial acral fibromyxomas are slowly growing, often painful lesions that range in size from 10 to 50 mm, typically found on the periungual region of digits.
- Micro: These tumours are lobulated, with a hypocellular to cellular stroma, and a variably collagenous to myxoid appearance. They may show infiltrative borders and involvement of underlying bone.
- Ancillary: Tumour cells are positive for CD34, CD99, and nestin, and often show a loss of RB1 expression.
Reference Gallery:
Superficial acral fibromyxoma. A lobular architecture is seen, with the tumour infiltrating into the subcutis and involving underlying bone.
Superficial acral fibromyxoma. A prominent myxoid stroma is observed.
Superficial acral fibromyxoma. A tumour with more collagenous stroma and a vaguely fascicular growth pattern.
Superficial acral fibromyxoma. A tumour with a more storiform growth pattern and conspicuous vasculature.
Cellular acral fibromyxoma. Acral fibromyxoma with increased cellularity.
Superficial acral fibromyxoma. The tumour cells are positive for CD34.
Superficial acral fibromyxoma. There is a fascicular growth of uniform spindle cells in a fibromyxoid stroma. Note the absence of cytological atypia.
Superficial acral fibromyxoma. The tumour cells show a loss of RB1 expression.

Q: A distinctive immunohistochemical finding in many cases of Superficial Acral Fibromyxoma is the characteristic loss of nuclear [...] expression.
Superficial acral fibromyxoma. The tumour cells show a loss of RB1 expression.
A: RB1
Back Extra: Superficial Acral Fibromyxoma
- Clinical: Superficial acral fibromyxomas are slowly growing, often painful lesions that range in size from 10 to 50 mm, typically found on the periungual region of digits.
- Micro: These tumours are lobulated, with a hypocellular to cellular stroma, and a variably collagenous to myxoid appearance. They may show infiltrative borders and involvement of underlying bone.
- Ancillary: Tumour cells are positive for CD34, CD99, and nestin, and often show a loss of RB1 expression.
Reference Gallery:
Superficial acral fibromyxoma. A lobular architecture is seen, with the tumour infiltrating into the subcutis and involving underlying bone.
Superficial acral fibromyxoma. A prominent myxoid stroma is observed.
Superficial acral fibromyxoma. A tumour with more collagenous stroma and a vaguely fascicular growth pattern.
Superficial acral fibromyxoma. A tumour with a more storiform growth pattern and conspicuous vasculature.
Cellular acral fibromyxoma. Acral fibromyxoma with increased cellularity.
Superficial acral fibromyxoma. The tumour cells are positive for CD34.
Superficial acral fibromyxoma. There is a fascicular growth of uniform spindle cells in a fibromyxoid stroma. Note the absence of cytological atypia.
Superficial acral fibromyxoma. The tumour cells show a loss of RB1 expression.

Q: Microscopically, Superficial CD34-positive fibroblastic tumour is characterized by pleomorphic spindle cells with abundant eosinophilic cytoplasm that typically has a distinctive [...] appearance.
Superficial CD34-positive fibroblastic tumour. Pleomorphic spindle cells with abundant granular to glassy eosinophilic cytoplasm and an occasional intranuclear pseudoinclusion.
Superficial CD34-positive fibroblastic tumour. Pleomorphic spindle cells with glassy cytoplasm and intranuclear pseudoinclusions.
A: granular or glassy
Back Extra: Superficial CD34-positive fibroblastic tumour
- Clinical: Superficial CD34-positive fibroblastic tumour typically presents as a slow-growing, painless mass in the superficial soft tissues, often with a long prebiopsy duration.
- Micro: The tumour is characterized by a proliferation of spindled and pleomorphic cells with abundant eosinophilic cytoplasm, often having a granular or ‘glassy’ appearance.
- Ancillary: These tumours invariably express CD34 and CADM3, and PRDM10 rearrangements are commonly identified.
Reference Gallery:
Superficial CD34-positive fibroblastic tumour. Well-circumscribed, cellular tumour in the dermis and subcutis, with peripheral lymphoid aggregates.
Superficial CD34-positive fibroblastic tumour. Highly cellular fascicles of spindle-shaped and pleomorphic cells with intervening inflammatory cells.
Superficial CD34-positive fibroblastic tumour. Pleomorphic spindle cells with abundant granular to glassy eosinophilic cytoplasm and an occasional intranuclear pseudoinclusion.
Superficial CD34-positive fibroblastic tumour. There are several pleomorphic cells with bizarre nuclear shapes, but no mitotic figures, and a mixed inflammatory infiltrate.
Superficial CD34-positive fibroblastic tumour. Pleomorphic spindle cells with glassy cytoplasm and intranuclear pseudoinclusions.
Superficial CD34-positive fibroblastic tumour / PRDM10-rearranged soft tissue tumour. Lipid-laden histiocytes and pleomorphic spindled cells.
Superficial CD34-positive fibroblastic tumour. Diffuse CD34 expression is consistently present.
Superficial CD34-positive fibroblastic tumour. Diffuse CADM3 expression is invariably present.

Q: Immunohistochemically, Superficial CD34-positive fibroblastic tumour is characterized by the invariable and diffuse expression of CD34 and [...].
Superficial CD34-positive fibroblastic tumour. Diffuse CD34 expression is consistently present.
Superficial CD34-positive fibroblastic tumour. Diffuse CADM3 expression is invariably present.
A: CADM3
Back Extra: Superficial CD34-positive fibroblastic tumour
- Clinical: Superficial CD34-positive fibroblastic tumour typically presents as a slow-growing, painless mass in the superficial soft tissues, often with a long prebiopsy duration.
- Micro: The tumour is characterized by a proliferation of spindled and pleomorphic cells with abundant eosinophilic cytoplasm, often having a granular or ‘glassy’ appearance.
- Ancillary: These tumours invariably express CD34 and CADM3, and PRDM10 rearrangements are commonly identified.
Reference Gallery:
Superficial CD34-positive fibroblastic tumour. Well-circumscribed, cellular tumour in the dermis and subcutis, with peripheral lymphoid aggregates.
Superficial CD34-positive fibroblastic tumour. Highly cellular fascicles of spindle-shaped and pleomorphic cells with intervening inflammatory cells.
Superficial CD34-positive fibroblastic tumour. Pleomorphic spindle cells with abundant granular to glassy eosinophilic cytoplasm and an occasional intranuclear pseudoinclusion.
Superficial CD34-positive fibroblastic tumour. There are several pleomorphic cells with bizarre nuclear shapes, but no mitotic figures, and a mixed inflammatory infiltrate.
Superficial CD34-positive fibroblastic tumour. Pleomorphic spindle cells with glassy cytoplasm and intranuclear pseudoinclusions.
Superficial CD34-positive fibroblastic tumour / PRDM10-rearranged soft tissue tumour. Lipid-laden histiocytes and pleomorphic spindled cells.
Superficial CD34-positive fibroblastic tumour. Diffuse CD34 expression is consistently present.
Superficial CD34-positive fibroblastic tumour. Diffuse CADM3 expression is invariably present.

Q: Superficial CD34-positive fibroblastic tumour is a distinctive mesenchymal neoplasm that commonly harbors recurrent gene rearrangements involving [...].
Superficial CD34-positive fibroblastic tumour / PRDM10-rearranged soft tissue tumour. Lipid-laden histiocytes and pleomorphic spindled cells.
A: PRDM10
Back Extra: Superficial CD34-positive fibroblastic tumour
- Clinical: Superficial CD34-positive fibroblastic tumour typically presents as a slow-growing, painless mass in the superficial soft tissues, often with a long prebiopsy duration.
- Micro: The tumour is characterized by a proliferation of spindled and pleomorphic cells with abundant eosinophilic cytoplasm, often having a granular or ‘glassy’ appearance.
- Ancillary: These tumours invariably express CD34 and CADM3, and PRDM10 rearrangements are commonly identified.
Reference Gallery:
Superficial CD34-positive fibroblastic tumour. Well-circumscribed, cellular tumour in the dermis and subcutis, with peripheral lymphoid aggregates.
Superficial CD34-positive fibroblastic tumour. Highly cellular fascicles of spindle-shaped and pleomorphic cells with intervening inflammatory cells.
Superficial CD34-positive fibroblastic tumour. Pleomorphic spindle cells with abundant granular to glassy eosinophilic cytoplasm and an occasional intranuclear pseudoinclusion.
Superficial CD34-positive fibroblastic tumour. There are several pleomorphic cells with bizarre nuclear shapes, but no mitotic figures, and a mixed inflammatory infiltrate.
Superficial CD34-positive fibroblastic tumour. Pleomorphic spindle cells with glassy cytoplasm and intranuclear pseudoinclusions.
Superficial CD34-positive fibroblastic tumour / PRDM10-rearranged soft tissue tumour. Lipid-laden histiocytes and pleomorphic spindled cells.
Superficial CD34-positive fibroblastic tumour. Diffuse CD34 expression is consistently present.
Superficial CD34-positive fibroblastic tumour. Diffuse CADM3 expression is invariably present.

Q: Histologically, Superficial Fibromatosis is characterized by a [...] growth pattern at low power.
Superficial fibromatosis. Low-power view showing a characteristic multinodular growth pattern.
A: multinodular
Back Extra: Superficial Fibromatosis
- Clinical: Palmar fibromatosis is characterized by small, painless coalescing nodules forming cords or bands in the subcutaneous tissue and underlying fascial plane.
- Micro: Superficial fibromatosis shows a characteristic multinodular growth pattern with spindle cells arranged in parallel fascicles within a collagenous stroma.
- Ancillary: Neoplastic cells in superficial fibromatosis may be positive for SMA and focally for desmin, and rarely show nuclear β-catenin expression.
Reference Gallery:
Superficial fibromatosis. Low-power view showing a characteristic multinodular growth pattern.
Superficial fibromatosis. Tumour cells are arranged in parallel fascicles separated by a collagenous stroma.
Superficial fibromatosis. The tumour is composed of spindle cells with bland ovoid nuclei with open chromatin and small nucleoli.
Superficial fibromatosis. Late-stage lesions are hypocellular and consist mostly of densely hyalinized fibrous tissue.

Q: At higher magnification, the bland spindle cells of Superficial Fibromatosis are characteristically arranged in [...] separated by a collagenous stroma.
Superficial fibromatosis. Tumour cells are arranged in parallel fascicles separated by a collagenous stroma.
Superficial fibromatosis. The tumour is composed of spindle cells with bland ovoid nuclei with open chromatin and small nucleoli.
A: parallel fascicles
Back Extra: Superficial Fibromatosis
- Clinical: Palmar fibromatosis is characterized by small, painless coalescing nodules forming cords or bands in the subcutaneous tissue and underlying fascial plane.
- Micro: Superficial fibromatosis shows a characteristic multinodular growth pattern with spindle cells arranged in parallel fascicles within a collagenous stroma.
- Ancillary: Neoplastic cells in superficial fibromatosis may be positive for SMA and focally for desmin, and rarely show nuclear β-catenin expression.
Reference Gallery:
Superficial fibromatosis. Low-power view showing a characteristic multinodular growth pattern.
Superficial fibromatosis. Tumour cells are arranged in parallel fascicles separated by a collagenous stroma.
Superficial fibromatosis. The tumour is composed of spindle cells with bland ovoid nuclei with open chromatin and small nucleoli.
Superficial fibromatosis. Late-stage lesions are hypocellular and consist mostly of densely hyalinized fibrous tissue.

Q: Late-stage lesions of Superficial Fibromatosis typically become hypocellular and consist mostly of densely [...] fibrous tissue.
Superficial fibromatosis. Late-stage lesions are hypocellular and consist mostly of densely hyalinized fibrous tissue.
A: hyalinized
Back Extra: Superficial Fibromatosis
- Clinical: Palmar fibromatosis is characterized by small, painless coalescing nodules forming cords or bands in the subcutaneous tissue and underlying fascial plane.
- Micro: Superficial fibromatosis shows a characteristic multinodular growth pattern with spindle cells arranged in parallel fascicles within a collagenous stroma.
- Ancillary: Neoplastic cells in superficial fibromatosis may be positive for SMA and focally for desmin, and rarely show nuclear β-catenin expression.
Reference Gallery:
Superficial fibromatosis. Low-power view showing a characteristic multinodular growth pattern.
Superficial fibromatosis. Tumour cells are arranged in parallel fascicles separated by a collagenous stroma.
Superficial fibromatosis. The tumour is composed of spindle cells with bland ovoid nuclei with open chromatin and small nucleoli.
Superficial fibromatosis. Late-stage lesions are hypocellular and consist mostly of densely hyalinized fibrous tissue.

Q: Histologically, angioleiomyoma is a well-circumscribed tumor characterized by concentric bundles of bland smooth muscle surrounding [...] of varying caliber.
Angioleiomyoma, solid subtype. Well-circumscribed lesion composed of compressed blood vessels surrounded by concentric bundles of smooth muscle.
Angioleiomyoma, venous subtype. Multiple blood vessels surrounded by concentric bland smooth muscle cells that blend with surrounding intervascular smooth muscle.
A: blood vessels
Back Extra: Angioleiomyoma
- Clinical: Approximately half of angioleiomyomas are painful and affect a wide age range, with peak incidence in the fourth through sixth decades of life.
- Micro: Angioleiomyomas are composed of bundles of bland, well-differentiated smooth muscle surrounding blood vessels of varying calibre, with three subtypes: solid, venous, and cavernous.
- Ancillary: Tumour cells are diffusely positive for actins (including SMA), calponin, and h-caldesmon, and negative for melanocytic markers.
Reference Gallery:
Angioleiomyoma, solid subtype. Well-circumscribed lesion composed of compressed blood vessels surrounded by concentric bundles of smooth muscle.
Angioleiomyoma, venous subtype. Multiple blood vessels surrounded by concentric bland smooth muscle cells that blend with surrounding intervascular smooth muscle.
Angioleiomyoma, venous subtype. Tumour cells are diffusely positive for SMA.

Q: Based on the architecture and caliber of the vascular channels, angioleiomyoma is classified into three histologic subtypes: solid, cavernous, and [...].
Angioleiomyoma, venous subtype. Multiple blood vessels surrounded by concentric bland smooth muscle cells that blend with surrounding intervascular smooth muscle.
A: venous
Back Extra: Angioleiomyoma
- Clinical: Approximately half of angioleiomyomas are painful and affect a wide age range, with peak incidence in the fourth through sixth decades of life.
- Micro: Angioleiomyomas are composed of bundles of bland, well-differentiated smooth muscle surrounding blood vessels of varying calibre, with three subtypes: solid, venous, and cavernous.
- Ancillary: Tumour cells are diffusely positive for actins (including SMA), calponin, and h-caldesmon, and negative for melanocytic markers.
Reference Gallery:
Angioleiomyoma, solid subtype. Well-circumscribed lesion composed of compressed blood vessels surrounded by concentric bundles of smooth muscle.
Angioleiomyoma, venous subtype. Multiple blood vessels surrounded by concentric bland smooth muscle cells that blend with surrounding intervascular smooth muscle.
Angioleiomyoma, venous subtype. Tumour cells are diffusely positive for SMA.

Q: In angioleiomyoma, the neoplastic smooth muscle cells are diffusely positive for actins, most notably [...] (smooth muscle actin).
Angioleiomyoma, venous subtype. Tumour cells are diffusely positive for SMA.
A: SMA
Back Extra: Angioleiomyoma
- Clinical: Approximately half of angioleiomyomas are painful and affect a wide age range, with peak incidence in the fourth through sixth decades of life.
- Micro: Angioleiomyomas are composed of bundles of bland, well-differentiated smooth muscle surrounding blood vessels of varying calibre, with three subtypes: solid, venous, and cavernous.
- Ancillary: Tumour cells are diffusely positive for actins (including SMA), calponin, and h-caldesmon, and negative for melanocytic markers.
Reference Gallery:
Angioleiomyoma, solid subtype. Well-circumscribed lesion composed of compressed blood vessels surrounded by concentric bundles of smooth muscle.
Angioleiomyoma, venous subtype. Multiple blood vessels surrounded by concentric bland smooth muscle cells that blend with surrounding intervascular smooth muscle.
Angioleiomyoma, venous subtype. Tumour cells are diffusely positive for SMA.

Q: In an immunosuppressed patient, a skin-colored subcutaneous nodule showing circumscribed fascicles of spindled myoid cells with admixed smaller rounded cells and intratumoral lymphocytes is characteristic of [...].
EBV-associated smooth muscle tumour. Circumscribed tumour composed of fascicles of spindled myoid cells.
EBV-associated smooth muscle tumour. Fascicles of spindle myoid cells and scattered intratumoural lymphocytes.
EBV-associated smooth muscle tumour. Smaller, rounded tumour cells with intervening lymphocytes.
A: EBV-associated smooth muscle tumor
Back Extra: EBV-associated smooth muscle tumour
- Clinical: EBV-associated smooth muscle tumour typically occurs in immunosuppressed patients, presenting as a skin-coloured nodule, often in the subcutaneous tissues of the limbs and trunk.
- Micro: The tumour is characterized by circumscribed fascicles of spindled myoid cells with an admixed population of smaller rounded cells and intratumoural lymphocytes.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) confirms EBV infection in neoplastic myoid cells.
Reference Gallery:
EBV-associated smooth muscle tumour. Circumscribed tumour composed of fascicles of spindled myoid cells.
EBV-associated smooth muscle tumour. Fascicles of spindle myoid cells and scattered intratumoural lymphocytes.
EBV-associated smooth muscle tumour. The tumour cells show strong staining with an antibody to SMA.
EBV-associated smooth muscle tumour. CD45 immunohistochemistry highlighting intratumoural lymphocytes.
EBV-associated smooth muscle tumour. The tumour cells show uniform nuclear signalling on in situ hybridization for EBV-encoded small RNA (EBER).
EBV-associated smooth muscle tumour. Smaller, rounded tumour cells with intervening lymphocytes.

Q: The diagnosis of an EBV-associated smooth muscle tumor is definitively confirmed by in situ hybridization for [...], which demonstrates uniform nuclear signaling in the neoplastic myoid cells.
EBV-associated smooth muscle tumour. The tumour cells show uniform nuclear signalling on in situ hybridization for EBV-encoded small RNA (EBER).
A: EBV-encoded small RNA (EBER)
Back Extra: EBV-associated smooth muscle tumour
- Clinical: EBV-associated smooth muscle tumour typically occurs in immunosuppressed patients, presenting as a skin-coloured nodule, often in the subcutaneous tissues of the limbs and trunk.
- Micro: The tumour is characterized by circumscribed fascicles of spindled myoid cells with an admixed population of smaller rounded cells and intratumoural lymphocytes.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) confirms EBV infection in neoplastic myoid cells.
Reference Gallery:
EBV-associated smooth muscle tumour. Circumscribed tumour composed of fascicles of spindled myoid cells.
EBV-associated smooth muscle tumour. Fascicles of spindle myoid cells and scattered intratumoural lymphocytes.
EBV-associated smooth muscle tumour. The tumour cells show strong staining with an antibody to SMA.
EBV-associated smooth muscle tumour. CD45 immunohistochemistry highlighting intratumoural lymphocytes.
EBV-associated smooth muscle tumour. The tumour cells show uniform nuclear signalling on in situ hybridization for EBV-encoded small RNA (EBER).
EBV-associated smooth muscle tumour. Smaller, rounded tumour cells with intervening lymphocytes.

Q: In an EBV-associated smooth muscle tumor, the spindled neoplastic cells typically demonstrate strong immunohistochemical positivity for [...], while the admixed intratumoral lymphocytes can be highlighted by CD45.
EBV-associated smooth muscle tumour. The tumour cells show strong staining with an antibody to SMA.
EBV-associated smooth muscle tumour. CD45 immunohistochemistry highlighting intratumoural lymphocytes.
A: smooth muscle actin (SMA)
Back Extra: EBV-associated smooth muscle tumour
- Clinical: EBV-associated smooth muscle tumour typically occurs in immunosuppressed patients, presenting as a skin-coloured nodule, often in the subcutaneous tissues of the limbs and trunk.
- Micro: The tumour is characterized by circumscribed fascicles of spindled myoid cells with an admixed population of smaller rounded cells and intratumoural lymphocytes.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) confirms EBV infection in neoplastic myoid cells.
Reference Gallery:
EBV-associated smooth muscle tumour. Circumscribed tumour composed of fascicles of spindled myoid cells.
EBV-associated smooth muscle tumour. Fascicles of spindle myoid cells and scattered intratumoural lymphocytes.
EBV-associated smooth muscle tumour. The tumour cells show strong staining with an antibody to SMA.
EBV-associated smooth muscle tumour. CD45 immunohistochemistry highlighting intratumoural lymphocytes.
EBV-associated smooth muscle tumour. The tumour cells show uniform nuclear signalling on in situ hybridization for EBV-encoded small RNA (EBER).
EBV-associated smooth muscle tumour. Smaller, rounded tumour cells with intervening lymphocytes.

Q: [...] is a dermal-based tumor consisting of fascicles of relatively uniform, eosinophilic spindled cells with cigar-shaped nuclei and perinuclear vacuoles, showing nuclear enlargement, hyperchromatism, and mitotic activity.
Atypical intradermal smooth muscle neoplasm. A dermal-based tumour typically consisting of well-differentiated smooth muscle cells with only moderate atypia.
Atypical intradermal smooth muscle neoplasm. There is moderate nuclear enlargement and hyperchromatism, and easily identified mitotic figures are seen.
A: Atypical intradermal smooth muscle neoplasm
Back Extra: Atypical intradermal smooth muscle neoplasm
- Clinical: Atypical intradermal smooth muscle neoplasms typically manifest as small (5–30 mm), solitary, and occasionally painful nodules on the trunk and lower extremities, most commonly affecting older men with a mean age of 56 years.
- Micro: These neoplasms are well-differentiated, consisting of fascicles of relatively uniform, eosinophilic spindled cells with perinuclear vacuoles and cigar-shaped nuclei, showing nuclear enlargement, hyperchromatism, and mitotic activity.
- Ancillary: Diagnostic criteria include a dermal-based tumour with an infiltrative growth pattern, variable expression of SMA, desmin, and caldesmon, and limited involvement of the subcutaneous fat.
Reference Gallery:
Atypical intradermal smooth muscle neoplasm. A dermal-based tumour typically consisting of well-differentiated smooth muscle cells with only moderate atypia.
Atypical intradermal smooth muscle neoplasm. As compared with their soft tissue counterparts, these tumours are typically less eosinophilic, resembling normal pilar smooth muscle (right).
Atypical intradermal smooth muscle neoplasm. Involvement of subcutaneous fat is the most important adverse prognostic feature in atypical intradermal smooth muscle neoplasm. Tumours with overt infiltration of subcutaneous fat have a metastatic risk and can be labelled cutaneous leiomyosarcoma instead.
Atypical intradermal smooth muscle neoplasm. There is moderate nuclear enlargement and hyperchromatism, and easily identified mitotic figures are seen.
Atypical intradermal smooth muscle neoplasm. Caldesmon is the most specific marker of smooth muscle differentiation.

Q: In an atypical intradermal smooth muscle neoplasm, overt infiltration of the [...] is the most important adverse prognostic feature, carrying a metastatic risk and prompting a diagnosis of cutaneous leiomyosarcoma.
Atypical intradermal smooth muscle neoplasm. Involvement of subcutaneous fat is the most important adverse prognostic feature in atypical intradermal smooth muscle neoplasm. Tumours with overt infiltration of subcutaneous fat have a metastatic risk and can be labelled cutaneous leiomyosarcoma instead.
A: subcutaneous fat
Back Extra: Atypical intradermal smooth muscle neoplasm
- Clinical: Atypical intradermal smooth muscle neoplasms typically manifest as small (5–30 mm), solitary, and occasionally painful nodules on the trunk and lower extremities, most commonly affecting older men with a mean age of 56 years.
- Micro: These neoplasms are well-differentiated, consisting of fascicles of relatively uniform, eosinophilic spindled cells with perinuclear vacuoles and cigar-shaped nuclei, showing nuclear enlargement, hyperchromatism, and mitotic activity.
- Ancillary: Diagnostic criteria include a dermal-based tumour with an infiltrative growth pattern, variable expression of SMA, desmin, and caldesmon, and limited involvement of the subcutaneous fat.
Reference Gallery:
Atypical intradermal smooth muscle neoplasm. A dermal-based tumour typically consisting of well-differentiated smooth muscle cells with only moderate atypia.
Atypical intradermal smooth muscle neoplasm. As compared with their soft tissue counterparts, these tumours are typically less eosinophilic, resembling normal pilar smooth muscle (right).
Atypical intradermal smooth muscle neoplasm. Involvement of subcutaneous fat is the most important adverse prognostic feature in atypical intradermal smooth muscle neoplasm. Tumours with overt infiltration of subcutaneous fat have a metastatic risk and can be labelled cutaneous leiomyosarcoma instead.
Atypical intradermal smooth muscle neoplasm. There is moderate nuclear enlargement and hyperchromatism, and easily identified mitotic figures are seen.
Atypical intradermal smooth muscle neoplasm. Caldesmon is the most specific marker of smooth muscle differentiation.

Q: To confirm the smooth muscle origin of an atypical intradermal smooth muscle neoplasm, immunohistochemistry for [...] is often utilized, as it is the most specific marker of smooth muscle differentiation.
Atypical intradermal smooth muscle neoplasm. Caldesmon is the most specific marker of smooth muscle differentiation.
A: caldesmon
Back Extra: Atypical intradermal smooth muscle neoplasm
- Clinical: Atypical intradermal smooth muscle neoplasms typically manifest as small (5–30 mm), solitary, and occasionally painful nodules on the trunk and lower extremities, most commonly affecting older men with a mean age of 56 years.
- Micro: These neoplasms are well-differentiated, consisting of fascicles of relatively uniform, eosinophilic spindled cells with perinuclear vacuoles and cigar-shaped nuclei, showing nuclear enlargement, hyperchromatism, and mitotic activity.
- Ancillary: Diagnostic criteria include a dermal-based tumour with an infiltrative growth pattern, variable expression of SMA, desmin, and caldesmon, and limited involvement of the subcutaneous fat.
Reference Gallery:
Atypical intradermal smooth muscle neoplasm. A dermal-based tumour typically consisting of well-differentiated smooth muscle cells with only moderate atypia.
Atypical intradermal smooth muscle neoplasm. As compared with their soft tissue counterparts, these tumours are typically less eosinophilic, resembling normal pilar smooth muscle (right).
Atypical intradermal smooth muscle neoplasm. Involvement of subcutaneous fat is the most important adverse prognostic feature in atypical intradermal smooth muscle neoplasm. Tumours with overt infiltration of subcutaneous fat have a metastatic risk and can be labelled cutaneous leiomyosarcoma instead.
Atypical intradermal smooth muscle neoplasm. There is moderate nuclear enlargement and hyperchromatism, and easily identified mitotic figures are seen.
Atypical intradermal smooth muscle neoplasm. Caldesmon is the most specific marker of smooth muscle differentiation.

Q: In a Cutaneous Leiomyoma, the intersecting fascicles of spindled smooth muscle cells feature characteristic [...] (blunt-ended) nuclei and glassy eosinophilic cytoplasm.
Cutaneous leiomyoma. Cutaneous (pilar) leiomyoma, closely resembling non-neoplastic pilar smooth muscle.
Cutaneous leiomyoma. Higher-power view of cutaneous leiomyoma, showing bland spindled cells with cigar-shaped nuclei and somewhat glassy-appearing eosinophilic cytoplasm.
A: cigar-shaped
Back Extra: Cutaneous Leiomyoma
- Clinical: Cutaneous leiomyomas are flesh-coloured to reddish-brown, firm, dome-shaped papules or nodules, often painful, and may be distributed in linear, segmental, or zosteriform patterns.
- Micro: Pilar leiomyomas are poorly circumscribed dermal nodules of intersecting, well-differentiated smooth muscle bundles with spindle cells, elongated, blunt-ended nuclei, and eosinophilic cytoplasm.
- Ancillary: Loss of fumarate hydratase (FH) expression and enhanced 2-succinocysteine (2SC) expression are useful in identifying hereditary leiomyomatosis and renal cell cancer syndrome.
Reference Gallery:
Cutaneous leiomyoma. Cutaneous (pilar) leiomyoma, closely resembling non-neoplastic pilar smooth muscle.
Cutaneous leiomyoma. Higher-power view of cutaneous leiomyoma, showing bland spindled cells with cigar-shaped nuclei and somewhat glassy-appearing eosinophilic cytoplasm.
Genital leiomyoma of the scrotum. Also known as dartoic leiomyoma, this is the scrotal counterpart of more common cutaneous lesions.
Genital leiomyoma. Circumscribed growth, low cellularity, and bland nuclear features in a scrotal leiomyoma.
Fumarate hydratase–deficient cutaneous leiomyoma. Fumarate hydratase–deficient leiomyoma occurring in a patient with hereditary leiomyomatosis and renal cell carcinoma syndrome. Note the moderate nuclear atypia and perinuclear haloes, characteristic features.
Fumarate hydratase–deficient cutaneous leiomyoma. Complete loss of fumarate hydratase expression in the tumour cells, with retained internal controls.
Fumarate hydratase–deficient cutaneous leiomyoma. Enhanced expression of 2-succinocysteine.

Q: A Cutaneous Leiomyoma displaying moderate nuclear atypia and perinuclear halos raises suspicion for Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) syndrome, characterized by the immunohistochemical loss of [...] expression.
Fumarate hydratase–deficient cutaneous leiomyoma. Fumarate hydratase–deficient leiomyoma occurring in a patient with hereditary leiomyomatosis and renal cell carcinoma syndrome. Note the moderate nuclear atypia and perinuclear haloes, characteristic features.
Fumarate hydratase–deficient cutaneous leiomyoma. Complete loss of fumarate hydratase expression in the tumour cells, with retained internal controls.
A: fumarate hydratase
Back Extra: Cutaneous Leiomyoma
- Clinical: Cutaneous leiomyomas are flesh-coloured to reddish-brown, firm, dome-shaped papules or nodules, often painful, and may be distributed in linear, segmental, or zosteriform patterns.
- Micro: Pilar leiomyomas are poorly circumscribed dermal nodules of intersecting, well-differentiated smooth muscle bundles with spindle cells, elongated, blunt-ended nuclei, and eosinophilic cytoplasm.
- Ancillary: Loss of fumarate hydratase (FH) expression and enhanced 2-succinocysteine (2SC) expression are useful in identifying hereditary leiomyomatosis and renal cell cancer syndrome.
Reference Gallery:
Cutaneous leiomyoma. Cutaneous (pilar) leiomyoma, closely resembling non-neoplastic pilar smooth muscle.
Cutaneous leiomyoma. Higher-power view of cutaneous leiomyoma, showing bland spindled cells with cigar-shaped nuclei and somewhat glassy-appearing eosinophilic cytoplasm.
Genital leiomyoma of the scrotum. Also known as dartoic leiomyoma, this is the scrotal counterpart of more common cutaneous lesions.
Genital leiomyoma. Circumscribed growth, low cellularity, and bland nuclear features in a scrotal leiomyoma.
Fumarate hydratase–deficient cutaneous leiomyoma. Fumarate hydratase–deficient leiomyoma occurring in a patient with hereditary leiomyomatosis and renal cell carcinoma syndrome. Note the moderate nuclear atypia and perinuclear haloes, characteristic features.
Fumarate hydratase–deficient cutaneous leiomyoma. Complete loss of fumarate hydratase expression in the tumour cells, with retained internal controls.
Fumarate hydratase–deficient cutaneous leiomyoma. Enhanced expression of 2-succinocysteine.

Q: In a fumarate hydratase–deficient Cutaneous Leiomyoma, immunohistochemical staining will characteristically demonstrate enhanced expression of [...].
Fumarate hydratase–deficient cutaneous leiomyoma. Enhanced expression of 2-succinocysteine.
A: 2-succinocysteine
Back Extra: Cutaneous Leiomyoma
- Clinical: Cutaneous leiomyomas are flesh-coloured to reddish-brown, firm, dome-shaped papules or nodules, often painful, and may be distributed in linear, segmental, or zosteriform patterns.
- Micro: Pilar leiomyomas are poorly circumscribed dermal nodules of intersecting, well-differentiated smooth muscle bundles with spindle cells, elongated, blunt-ended nuclei, and eosinophilic cytoplasm.
- Ancillary: Loss of fumarate hydratase (FH) expression and enhanced 2-succinocysteine (2SC) expression are useful in identifying hereditary leiomyomatosis and renal cell cancer syndrome.
Reference Gallery:
Cutaneous leiomyoma. Cutaneous (pilar) leiomyoma, closely resembling non-neoplastic pilar smooth muscle.
Cutaneous leiomyoma. Higher-power view of cutaneous leiomyoma, showing bland spindled cells with cigar-shaped nuclei and somewhat glassy-appearing eosinophilic cytoplasm.
Genital leiomyoma of the scrotum. Also known as dartoic leiomyoma, this is the scrotal counterpart of more common cutaneous lesions.
Genital leiomyoma. Circumscribed growth, low cellularity, and bland nuclear features in a scrotal leiomyoma.
Fumarate hydratase–deficient cutaneous leiomyoma. Fumarate hydratase–deficient leiomyoma occurring in a patient with hereditary leiomyomatosis and renal cell carcinoma syndrome. Note the moderate nuclear atypia and perinuclear haloes, characteristic features.
Fumarate hydratase–deficient cutaneous leiomyoma. Complete loss of fumarate hydratase expression in the tumour cells, with retained internal controls.
Fumarate hydratase–deficient cutaneous leiomyoma. Enhanced expression of 2-succinocysteine.

Q: Clinically, a classic presentation of Smooth Muscle Hamartoma is a congenital plaque featuring perifollicular papules and prominent [...].
Smooth muscle hamartoma. A large congenital pinkish plaque on the trunk, with long, thin, light hair emanating from its surface.
A: hypertrichosis
Back Extra: Smooth Muscle Hamartoma
- Clinical: Smooth muscle hamartoma (SMH) is typically a congenital, slightly indurated, and pigmented or flesh-colored plaque, often presenting with perifollicular papules and hypertrichosis.
- Micro: Histologically, SMH shows haphazardly arranged, mature smooth muscle bundles in the dermis, often associated with the pilosebaceous units, and may show focal retraction artefact.
- Ancillary: A subset of congenital SMHs result from postzygotic ACTB mutations, which are also found in Becker nevi, suggesting a biological relationship.
Reference Gallery:
Smooth muscle hamartoma. A large congenital pinkish plaque on the trunk, with long, thin, light hair emanating from its surface.
Smooth muscle hamartoma. The lesion occupies the full depth of the reticular dermis and, focally, the superficial subcutis. The overlying epidermis is normal.
Smooth muscle hamartoma. The lesion occupies the full depth of the reticular dermis and, focally, the superficial subcutis. The overlying epidermis is normal. There are small and horizontally arranged smooth muscle bundles, surrounded by focal retraction artefact.
Smooth muscle hamartoma. There is focal retraction artefact around the smooth muscle bundles.
Smooth muscle hamartoma. Positive immunohistochemistry with an antibody to SMA.
Smooth muscle hamartoma. Smooth muscle bundles are haphazardly arranged, scattered throughout the dermis and superficial subcutis. The overlying epidermis is acanthotic.
Smooth muscle hamartoma. Strongly positive staining of the smooth muscle bundles with an antibody to calponin.

Q: In Smooth Muscle Hamartoma, the characteristic histologic finding is haphazardly arranged, mature smooth muscle bundles in the dermis that frequently display focal [...].
Smooth muscle hamartoma. The lesion occupies the full depth of the reticular dermis and, focally, the superficial subcutis. The overlying epidermis is normal. There are small and horizontally arranged smooth muscle bundles, surrounded by focal retraction artefact.
Smooth muscle hamartoma. There is focal retraction artefact around the smooth muscle bundles.
A: retraction artifact
Back Extra: Smooth Muscle Hamartoma
- Clinical: Smooth muscle hamartoma (SMH) is typically a congenital, slightly indurated, and pigmented or flesh-colored plaque, often presenting with perifollicular papules and hypertrichosis.
- Micro: Histologically, SMH shows haphazardly arranged, mature smooth muscle bundles in the dermis, often associated with the pilosebaceous units, and may show focal retraction artefact.
- Ancillary: A subset of congenital SMHs result from postzygotic ACTB mutations, which are also found in Becker nevi, suggesting a biological relationship.
Reference Gallery:
Smooth muscle hamartoma. A large congenital pinkish plaque on the trunk, with long, thin, light hair emanating from its surface.
Smooth muscle hamartoma. The lesion occupies the full depth of the reticular dermis and, focally, the superficial subcutis. The overlying epidermis is normal.
Smooth muscle hamartoma. The lesion occupies the full depth of the reticular dermis and, focally, the superficial subcutis. The overlying epidermis is normal. There are small and horizontally arranged smooth muscle bundles, surrounded by focal retraction artefact.
Smooth muscle hamartoma. There is focal retraction artefact around the smooth muscle bundles.
Smooth muscle hamartoma. Positive immunohistochemistry with an antibody to SMA.
Smooth muscle hamartoma. Smooth muscle bundles are haphazardly arranged, scattered throughout the dermis and superficial subcutis. The overlying epidermis is acanthotic.
Smooth muscle hamartoma. Strongly positive staining of the smooth muscle bundles with an antibody to calponin.

Q: In Smooth Muscle Hamartoma, the haphazardly arranged mature dermal bundles demonstrate strong immunohistochemical positivity for smooth muscle markers such as SMA and [...].
Smooth muscle hamartoma. Positive immunohistochemistry with an antibody to SMA.
Smooth muscle hamartoma. Strongly positive staining of the smooth muscle bundles with an antibody to calponin.
A: calponin
Back Extra: Smooth Muscle Hamartoma
- Clinical: Smooth muscle hamartoma (SMH) is typically a congenital, slightly indurated, and pigmented or flesh-colored plaque, often presenting with perifollicular papules and hypertrichosis.
- Micro: Histologically, SMH shows haphazardly arranged, mature smooth muscle bundles in the dermis, often associated with the pilosebaceous units, and may show focal retraction artefact.
- Ancillary: A subset of congenital SMHs result from postzygotic ACTB mutations, which are also found in Becker nevi, suggesting a biological relationship.
Reference Gallery:
Smooth muscle hamartoma. A large congenital pinkish plaque on the trunk, with long, thin, light hair emanating from its surface.
Smooth muscle hamartoma. The lesion occupies the full depth of the reticular dermis and, focally, the superficial subcutis. The overlying epidermis is normal.
Smooth muscle hamartoma. The lesion occupies the full depth of the reticular dermis and, focally, the superficial subcutis. The overlying epidermis is normal. There are small and horizontally arranged smooth muscle bundles, surrounded by focal retraction artefact.
Smooth muscle hamartoma. There is focal retraction artefact around the smooth muscle bundles.
Smooth muscle hamartoma. Positive immunohistochemistry with an antibody to SMA.
Smooth muscle hamartoma. Smooth muscle bundles are haphazardly arranged, scattered throughout the dermis and superficial subcutis. The overlying epidermis is acanthotic.
Smooth muscle hamartoma. Strongly positive staining of the smooth muscle bundles with an antibody to calponin.

Q: In Dermal Hyperneury / Epithelial Sheath Neuroma, the epithelial sheath neuroma lesions are characterized histologically by enlarged nerve fibers that are uniquely ensheathed by mature [...].
Epithelial sheath neuroma. Enlarged nerve fibres are ensheathed by squamous epithelium.
A: squamous epithelium
Back Extra: Dermal Hyperneury / Epithelial Sheath Neuroma
- Clinical: Dermal hyperneury and epithelial sheath neuroma present as single or multiple, asymptomatic lesions. Patients may experience itching, intermittent burning, or pain. Most patients are in their seventh decade of life, with a slight female preponderance.
- Micro: Histologically, dermal hyperneury shows increased nerve fibres that are 1.5–4 times larger than normal. Epithelial sheath neuroma features enlarged nerve fibres ensheathed by mature squamous epithelium.
- Ancillary: Multiple lesions in younger patients should prompt investigation for genetic syndromes and molecular alterations, particularly involving PTEN-regulated and RET-regulated signalling pathways.
Reference Gallery:
Dermal hyperneury. Prominent and enlarged dermal nerve fibres.
Dermal hyperneury. Intraneural mucin accumulation is evident in some cases of dermal hyperneury.
Epithelial sheath neuroma. Enlarged nerve fibres are ensheathed by squamous epithelium.

Q: In Dermal Hyperneury / Epithelial Sheath Neuroma, the dermal hyperneury component features prominent, enlarged dermal nerve fibers that may sometimes demonstrate secondary accumulation of intraneural [...].
Dermal hyperneury. Prominent and enlarged dermal nerve fibres.
Dermal hyperneury. Intraneural mucin accumulation is evident in some cases of dermal hyperneury.
A: mucin
Back Extra: Dermal Hyperneury / Epithelial Sheath Neuroma
- Clinical: Dermal hyperneury and epithelial sheath neuroma present as single or multiple, asymptomatic lesions. Patients may experience itching, intermittent burning, or pain. Most patients are in their seventh decade of life, with a slight female preponderance.
- Micro: Histologically, dermal hyperneury shows increased nerve fibres that are 1.5–4 times larger than normal. Epithelial sheath neuroma features enlarged nerve fibres ensheathed by mature squamous epithelium.
- Ancillary: Multiple lesions in younger patients should prompt investigation for genetic syndromes and molecular alterations, particularly involving PTEN-regulated and RET-regulated signalling pathways.
Reference Gallery:
Dermal hyperneury. Prominent and enlarged dermal nerve fibres.
Dermal hyperneury. Intraneural mucin accumulation is evident in some cases of dermal hyperneury.
Epithelial sheath neuroma. Enlarged nerve fibres are ensheathed by squamous epithelium.

Q: Microscopically, Dermal Nerve Sheath Myxoma displays a characteristic [...] growth pattern consisting of abundant myxoid matrix surrounded by a dense fibrous border.
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
A: multinodular
Back Extra: Dermal Nerve Sheath Myxoma
- Clinical: Dermal nerve sheath myxomas are small, superficial, slow-growing masses, often painless, located in the distal extremities, particularly the fingers.
- Micro: Characterized by a multinodular growth pattern, abundant myxoid matrix, and a dense fibrous border. Neoplastic Schwann cells are arranged in cords and syncytial-like aggregates, with some cells having a ring-like appearance.
- Ancillary: Diffusely positive for S100, with GFAP and CD57 often positive. AE1/AE3 can be positive in rare cells, and the fibrous capsule may show scattered EMA-positive cells.
Reference Gallery:
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. The neoplastic Schwann cells express S100.

Q: In Dermal Nerve Sheath Myxoma, the neoplastic Schwann cells are arranged in cords and syncytia, with some cells exhibiting a [...] appearance that resembles fat cells.
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
A: ring-like
Back Extra: Dermal Nerve Sheath Myxoma
- Clinical: Dermal nerve sheath myxomas are small, superficial, slow-growing masses, often painless, located in the distal extremities, particularly the fingers.
- Micro: Characterized by a multinodular growth pattern, abundant myxoid matrix, and a dense fibrous border. Neoplastic Schwann cells are arranged in cords and syncytial-like aggregates, with some cells having a ring-like appearance.
- Ancillary: Diffusely positive for S100, with GFAP and CD57 often positive. AE1/AE3 can be positive in rare cells, and the fibrous capsule may show scattered EMA-positive cells.
Reference Gallery:
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. The neoplastic Schwann cells express S100.

Q: Immunohistochemical staining of a Dermal Nerve Sheath Myxoma demonstrates diffuse positivity for [...].
Dermal nerve sheath myxoma. The neoplastic Schwann cells express S100.
A: S100
Back Extra: Dermal Nerve Sheath Myxoma
- Clinical: Dermal nerve sheath myxomas are small, superficial, slow-growing masses, often painless, located in the distal extremities, particularly the fingers.
- Micro: Characterized by a multinodular growth pattern, abundant myxoid matrix, and a dense fibrous border. Neoplastic Schwann cells are arranged in cords and syncytial-like aggregates, with some cells having a ring-like appearance.
- Ancillary: Diffusely positive for S100, with GFAP and CD57 often positive. AE1/AE3 can be positive in rare cells, and the fibrous capsule may show scattered EMA-positive cells.
Reference Gallery:
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. Low/intermediate-power view of a dermal nerve sheath myxoma. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. The neoplastic Schwann cells express S100.

Q: A granular cell tumor often induces striking [...] in the overlying squamous epithelium, which can histologically mimic invasive squamous cell carcinoma.
Granular cell tumour. This biopsy of a tongue lesion shows pseudoepitheliomatous hyperplasia, mimicking invasive carcinoma. Note the sheets of granular cell tumour cells with extensive granular cytoplasm surrounding the nests of hyperplastic squamous epithelium.
Granular cell tumour. A dermal example with extensive pseudoepitheliomatous hyperplasia.
A: pseudoepitheliomatous hyperplasia
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours typically manifest as solitary, firm, skin-coloured to reddish-brown painless nodules, most common in African Americans and in the fourth to sixth decades of life.
- Micro: Composed of sheets, nests, and trabeculae of large epithelioid to polygonal cells with abundant granular eosinophilic cytoplasm and centrally located nuclei.
- Ancillary: Strong and diffuse positivity for S100, SOX10, inhibin, and calretinin, with a low Ki-67 proliferation index (< 2%) in benign forms.
Reference Gallery:
Granular cell tumour. The squamous epithelium overlying the tumour shows basal cell hyperplasia.
Granular cell tumour. The tumour is composed of polygonal cells with hyperchromatic nuclei and abundant granular eosinophilic cytoplasm. Note the occasional cells with degenerative nuclear atypia.
Granular cell tumour. This biopsy of a tongue lesion shows pseudoepitheliomatous hyperplasia, mimicking invasive carcinoma. Note the sheets of granular cell tumour cells with extensive granular cytoplasm surrounding the nests of hyperplastic squamous epithelium.
Granular cell tumour. As seen here, S100 immunohistochemistry is diffusely and strongly positive in granular cell tumour.
Malignant granular cell tumour. This malignant granular cell tumour shows cytological pleomorphism and extensive mitotic activity, including atypical mitotic figures.
Granular cell tumour. Granular cell tumour infiltrating fibrous tissue and composed of sheets of cells with small round nuclei and extensive pink cytoplasm.
Granular cell tumour. Granular cell tumour composed of nests and sheets of cells with small round nuclei and extensively granular cytoplasm.
Granular cell tumour. A dermal example with extensive pseudoepitheliomatous hyperplasia.
Granular cell tumour. Perineural infiltration is common.

Q: In addition to SOX10, inhibin, and calretinin, a granular cell tumor classically demonstrates strong and diffuse immunohistochemical positivity for [...].
Granular cell tumour. As seen here, S100 immunohistochemistry is diffusely and strongly positive in granular cell tumour.
A: S100
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours typically manifest as solitary, firm, skin-coloured to reddish-brown painless nodules, most common in African Americans and in the fourth to sixth decades of life.
- Micro: Composed of sheets, nests, and trabeculae of large epithelioid to polygonal cells with abundant granular eosinophilic cytoplasm and centrally located nuclei.
- Ancillary: Strong and diffuse positivity for S100, SOX10, inhibin, and calretinin, with a low Ki-67 proliferation index (< 2%) in benign forms.
Reference Gallery:
Granular cell tumour. The squamous epithelium overlying the tumour shows basal cell hyperplasia.
Granular cell tumour. The tumour is composed of polygonal cells with hyperchromatic nuclei and abundant granular eosinophilic cytoplasm. Note the occasional cells with degenerative nuclear atypia.
Granular cell tumour. This biopsy of a tongue lesion shows pseudoepitheliomatous hyperplasia, mimicking invasive carcinoma. Note the sheets of granular cell tumour cells with extensive granular cytoplasm surrounding the nests of hyperplastic squamous epithelium.
Granular cell tumour. As seen here, S100 immunohistochemistry is diffusely and strongly positive in granular cell tumour.
Malignant granular cell tumour. This malignant granular cell tumour shows cytological pleomorphism and extensive mitotic activity, including atypical mitotic figures.
Granular cell tumour. Granular cell tumour infiltrating fibrous tissue and composed of sheets of cells with small round nuclei and extensive pink cytoplasm.
Granular cell tumour. Granular cell tumour composed of nests and sheets of cells with small round nuclei and extensively granular cytoplasm.
Granular cell tumour. A dermal example with extensive pseudoepitheliomatous hyperplasia.
Granular cell tumour. Perineural infiltration is common.

Q: A benign skin or mucosal neoplasm composed of nests and sheets of polygonal cells with abundant granular eosinophilic cytoplasm and small round centrally located nuclei is characteristic of a [...].
Granular cell tumour. The tumour is composed of polygonal cells with hyperchromatic nuclei and abundant granular eosinophilic cytoplasm. Note the occasional cells with degenerative nuclear atypia.
Granular cell tumour. Granular cell tumour composed of nests and sheets of cells with small round nuclei and extensively granular cytoplasm.
A: granular cell tumor
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours typically manifest as solitary, firm, skin-coloured to reddish-brown painless nodules, most common in African Americans and in the fourth to sixth decades of life.
- Micro: Composed of sheets, nests, and trabeculae of large epithelioid to polygonal cells with abundant granular eosinophilic cytoplasm and centrally located nuclei.
- Ancillary: Strong and diffuse positivity for S100, SOX10, inhibin, and calretinin, with a low Ki-67 proliferation index (< 2%) in benign forms.
Reference Gallery:
Granular cell tumour. The squamous epithelium overlying the tumour shows basal cell hyperplasia.
Granular cell tumour. The tumour is composed of polygonal cells with hyperchromatic nuclei and abundant granular eosinophilic cytoplasm. Note the occasional cells with degenerative nuclear atypia.
Granular cell tumour. This biopsy of a tongue lesion shows pseudoepitheliomatous hyperplasia, mimicking invasive carcinoma. Note the sheets of granular cell tumour cells with extensive granular cytoplasm surrounding the nests of hyperplastic squamous epithelium.
Granular cell tumour. As seen here, S100 immunohistochemistry is diffusely and strongly positive in granular cell tumour.
Malignant granular cell tumour. This malignant granular cell tumour shows cytological pleomorphism and extensive mitotic activity, including atypical mitotic figures.
Granular cell tumour. Granular cell tumour infiltrating fibrous tissue and composed of sheets of cells with small round nuclei and extensive pink cytoplasm.
Granular cell tumour. Granular cell tumour composed of nests and sheets of cells with small round nuclei and extensively granular cytoplasm.
Granular cell tumour. A dermal example with extensive pseudoepitheliomatous hyperplasia.
Granular cell tumour. Perineural infiltration is common.

Q: In the schwannoma/perineurioma variant of a Hybrid Nerve Sheath Tumour, dual immunolabeling reveals an intimately admixed population of cells with S100 highlighting the Schwann cells and [...] highlighting the perineurial cells.
Hybrid schwannoma/perineurioma. Double immunolabelling for S100 (red) and EMA (brown) highlights alternating Schwann cells and perineurial cells, respectively.
A: EMA
Back Extra: Hybrid Nerve Sheath Tumour
- Clinical: Hybrid nerve sheath tumours are rare, painless masses in subcutaneous tissue or dermis, often seen in young adults with equal sex distribution.
- Micro: The tumour shows a mixed population of Schwann cells and perineurial cells, with a storiform or fascicular growth pattern and alternating cell types highlighted by immunohistochemistry.
- Ancillary: VGLL3 gene rearrangement is found in most cases of hybrid perineurioma/schwannoma, aiding in diagnosis.
Reference Gallery:
Hybrid schwannoma/neurofibroma. Solid nodule of Schwann cell proliferation surrounded by loose hypocellular tumour.
Hybrid schwannoma/neurofibroma. S100 stain showing diffuse staining in the solid Schwann cell nodule and a mixed population of cells (S100-positive and S100-negative) in surrounding loose areas.
Hybrid schwannoma/perineurioma. The tumour shows a storiform architecture, similar to that of perineurioma of soft tissue.
Hybrid schwannoma/perineurioma. Many of the tumour cells contain plump, tapering nuclei and eosinophilic cytoplasm, typical of Schwann cells. The perineurial cell component is often inconspicuous.
Hybrid schwannoma/perineurioma. Double immunolabelling for S100 (red) and EMA (brown) highlights alternating Schwann cells and perineurial cells, respectively.

Q: A peripheral nerve sheath tumor displaying a discrete, solid nodule of Schwann cells (diffusely S100-positive) surrounded by a loose, hypocellular background (showing a mixed population of S100-positive and negative cells) is characteristic of the schwannoma/neurofibroma variant of a [...].
Hybrid schwannoma/neurofibroma. Solid nodule of Schwann cell proliferation surrounded by loose hypocellular tumour.
Hybrid schwannoma/neurofibroma. S100 stain showing diffuse staining in the solid Schwann cell nodule and a mixed population of cells (S100-positive and S100-negative) in surrounding loose areas.
A: Hybrid Nerve Sheath Tumour
Back Extra: Hybrid Nerve Sheath Tumour
- Clinical: Hybrid nerve sheath tumours are rare, painless masses in subcutaneous tissue or dermis, often seen in young adults with equal sex distribution.
- Micro: The tumour shows a mixed population of Schwann cells and perineurial cells, with a storiform or fascicular growth pattern and alternating cell types highlighted by immunohistochemistry.
- Ancillary: VGLL3 gene rearrangement is found in most cases of hybrid perineurioma/schwannoma, aiding in diagnosis.
Reference Gallery:
Hybrid schwannoma/neurofibroma. Solid nodule of Schwann cell proliferation surrounded by loose hypocellular tumour.
Hybrid schwannoma/neurofibroma. S100 stain showing diffuse staining in the solid Schwann cell nodule and a mixed population of cells (S100-positive and S100-negative) in surrounding loose areas.
Hybrid schwannoma/perineurioma. The tumour shows a storiform architecture, similar to that of perineurioma of soft tissue.
Hybrid schwannoma/perineurioma. Many of the tumour cells contain plump, tapering nuclei and eosinophilic cytoplasm, typical of Schwann cells. The perineurial cell component is often inconspicuous.
Hybrid schwannoma/perineurioma. Double immunolabelling for S100 (red) and EMA (brown) highlights alternating Schwann cells and perineurial cells, respectively.

Q: In the schwannoma/perineurioma variant of a Hybrid Nerve Sheath Tumour, the tumor typically exhibits a [...] or fascicular growth pattern, composed of plump, tapering Schwann cells and inconspicuous perineurial cells.
Hybrid schwannoma/perineurioma. The tumour shows a storiform architecture, similar to that of perineurioma of soft tissue.
Hybrid schwannoma/perineurioma. Many of the tumour cells contain plump, tapering nuclei and eosinophilic cytoplasm, typical of Schwann cells. The perineurial cell component is often inconspicuous.
A: storiform
Back Extra: Hybrid Nerve Sheath Tumour
- Clinical: Hybrid nerve sheath tumours are rare, painless masses in subcutaneous tissue or dermis, often seen in young adults with equal sex distribution.
- Micro: The tumour shows a mixed population of Schwann cells and perineurial cells, with a storiform or fascicular growth pattern and alternating cell types highlighted by immunohistochemistry.
- Ancillary: VGLL3 gene rearrangement is found in most cases of hybrid perineurioma/schwannoma, aiding in diagnosis.
Reference Gallery:
Hybrid schwannoma/neurofibroma. Solid nodule of Schwann cell proliferation surrounded by loose hypocellular tumour.
Hybrid schwannoma/neurofibroma. S100 stain showing diffuse staining in the solid Schwann cell nodule and a mixed population of cells (S100-positive and S100-negative) in surrounding loose areas.
Hybrid schwannoma/perineurioma. The tumour shows a storiform architecture, similar to that of perineurioma of soft tissue.
Hybrid schwannoma/perineurioma. Many of the tumour cells contain plump, tapering nuclei and eosinophilic cytoplasm, typical of Schwann cells. The perineurial cell component is often inconspicuous.
Hybrid schwannoma/perineurioma. Double immunolabelling for S100 (red) and EMA (brown) highlights alternating Schwann cells and perineurial cells, respectively.

Q: Microscopically, conventional Malignant Peripheral Nerve Sheath Tumor features spindle cells arranged in alternating hypercellular and hypocellular areas with characteristic [...].
Malignant peripheral nerve sheath tumour. Higher magnification demonstrates the alternating hypercellular and hypocellular areas.
Malignant peripheral nerve sheath tumour. A high-power view shows the characteristic “wavy” nuclei.
A: "wavy" nuclei
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumour (MPNST) is often associated with localized swelling and pain, but can be asymptomatic. It is more common in older patients and those with neurofibromatosis type 1 (NF1).
- Micro: MPNSTs are typically composed of fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas, and characteristic 'wavy' nuclei. Epithelioid MPNST shows plump, epithelioid cells with abundant eosinophilic cytoplasm.
- Ancillary: MPNSTs may be positive for S100 and SOX10, but expression is often patchy. Epithelioid MPNSTs show strong and diffuse expression of S100 and SOX10, but often lose SMARCB1 expression.
Reference Gallery:
Epithelioid malignant peripheral nerve sheath tumour. The cells are epithelioid, with eosinophilic cytoplasm and large nuclei with prominent nucleoli, mimicking a malignant melanoma.
Epithelioid malignant peripheral nerve sheath tumour. A SOX10 stain shows diffuse expression by the tumour cells. This is in contrast to the spindle cell subtype, which shows very focal or no expression of SOX10. The same staining pattern is seen with S100.
Epithelioid malignant peripheral nerve sheath tumour. SMARCB1 (INI1) immunohistochemistry shows loss of expression by the neoplastic cells. This is a frequent finding in the epithelioid subtype.
Malignant peripheral nerve sheath tumour. Tumour arising in a patient with neurofibromatosis type 1. The tumour involves the dermis and subcutaneous tissue. It is composed of spindle-shaped cells with alternating hypercellular and hypocellular areas.
Malignant peripheral nerve sheath tumour. Higher magnification demonstrates the alternating hypercellular and hypocellular areas.
Malignant peripheral nerve sheath tumour. A high-power view shows the characteristic “wavy” nuclei.

Q: The epithelioid variant of Malignant Peripheral Nerve Sheath Tumor mimics melanoma with strong SOX10 positivity but frequently demonstrates loss of [...] (INI1) expression.
Epithelioid malignant peripheral nerve sheath tumour. The cells are epithelioid, with eosinophilic cytoplasm and large nuclei with prominent nucleoli, mimicking a malignant melanoma.
Epithelioid malignant peripheral nerve sheath tumour. A SOX10 stain shows diffuse expression by the tumour cells. This is in contrast to the spindle cell subtype, which shows very focal or no expression of SOX10. The same staining pattern is seen with S100.
Epithelioid malignant peripheral nerve sheath tumour. SMARCB1 (INI1) immunohistochemistry shows loss of expression by the neoplastic cells. This is a frequent finding in the epithelioid subtype.
A: SMARCB1
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumour (MPNST) is often associated with localized swelling and pain, but can be asymptomatic. It is more common in older patients and those with neurofibromatosis type 1 (NF1).
- Micro: MPNSTs are typically composed of fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas, and characteristic 'wavy' nuclei. Epithelioid MPNST shows plump, epithelioid cells with abundant eosinophilic cytoplasm.
- Ancillary: MPNSTs may be positive for S100 and SOX10, but expression is often patchy. Epithelioid MPNSTs show strong and diffuse expression of S100 and SOX10, but often lose SMARCB1 expression.
Reference Gallery:
Epithelioid malignant peripheral nerve sheath tumour. The cells are epithelioid, with eosinophilic cytoplasm and large nuclei with prominent nucleoli, mimicking a malignant melanoma.
Epithelioid malignant peripheral nerve sheath tumour. A SOX10 stain shows diffuse expression by the tumour cells. This is in contrast to the spindle cell subtype, which shows very focal or no expression of SOX10. The same staining pattern is seen with S100.
Epithelioid malignant peripheral nerve sheath tumour. SMARCB1 (INI1) immunohistochemistry shows loss of expression by the neoplastic cells. This is a frequent finding in the epithelioid subtype.
Malignant peripheral nerve sheath tumour. Tumour arising in a patient with neurofibromatosis type 1. The tumour involves the dermis and subcutaneous tissue. It is composed of spindle-shaped cells with alternating hypercellular and hypocellular areas.
Malignant peripheral nerve sheath tumour. Higher magnification demonstrates the alternating hypercellular and hypocellular areas.
Malignant peripheral nerve sheath tumour. A high-power view shows the characteristic “wavy” nuclei.

Q: In Merkel Cell Carcinoma, the tumor cells classically display nuclear molding and a fine stippled ([...]) chromatin pattern.
Merkel cell carcinoma. The tumour cells display a fine stippled chromatin pattern. There is nuclear moulding.
Merkel cell carcinoma. The tumour cells display a pale salt-and-pepper chromatin pattern; there is focal rosette-like arrangement of the nuclei; several mitotic figures are present.
A: salt-and-pepper
Back Extra: Merkel Cell Carcinoma
- Clinical: Merkel cell carcinoma typically appears as a rapidly growing flesh-colored or violaceous nodule or plaque, most commonly on sun-damaged skin, especially the head and neck, extremities, and trunk.
- Micro: The tumour cells display a fine stippled (salt-and-pepper) chromatin pattern, nuclear moulding, and numerous mitotic figures. They often form large or small aggregates and may display a trabecular growth pattern.
- Ancillary: Immunohistochemically, tumour cells are uniformly immunoreactive with CM2B4 (MCPyV large T antigen) and CK20 in a perinuclear dot-like pattern. They also express epithelial markers and neuroendocrine markers.
Reference Gallery:
Merkel cell carcinoma. Nodule on the upper lip.
Merkel cell carcinoma. The tumour cells display a fine stippled chromatin pattern. There is nuclear moulding.
Merkel cell carcinoma. Involvement of the dermis and subcutis.
Merkel cell carcinoma. The tumour cells display a pale salt-and-pepper chromatin pattern; there is focal rosette-like arrangement of the nuclei; several mitotic figures are present.
Merkel cell carcinoma. The tumour cells are uniformly immunoreactive with CM2B4 (a monoclonal antibody to the MCPyV large T antigen).
Merkel cell carcinoma. The tumour cells display a trabecular architecture.
Merkel cell carcinoma. Combined neuroendocrine and invasive squamous cell carcinoma. A minor component of the tumour shows squamous differentiation.
Merkel cell carcinoma. Higher magnification shows nuclear labelling of the tumour cells with CM2B4.
Merkel cell carcinoma. The tumour cells are immunoreactive for CK20 in a perinuclear dot-like pattern.
Merkel cell carcinoma. Malignant blue cell tumour in dermis and subcutis.
Merkel cell carcinoma. Epidermotropic Merkel cell carcinoma. Tumour cells are present in both the epidermis and dermis.

Q: Immunohistochemically, Merkel Cell Carcinoma is classically positive for CK20 in a characteristic [...] pattern.
Merkel cell carcinoma. The tumour cells are immunoreactive for CK20 in a perinuclear dot-like pattern.
A: perinuclear dot-like
Back Extra: Merkel Cell Carcinoma
- Clinical: Merkel cell carcinoma typically appears as a rapidly growing flesh-colored or violaceous nodule or plaque, most commonly on sun-damaged skin, especially the head and neck, extremities, and trunk.
- Micro: The tumour cells display a fine stippled (salt-and-pepper) chromatin pattern, nuclear moulding, and numerous mitotic figures. They often form large or small aggregates and may display a trabecular growth pattern.
- Ancillary: Immunohistochemically, tumour cells are uniformly immunoreactive with CM2B4 (MCPyV large T antigen) and CK20 in a perinuclear dot-like pattern. They also express epithelial markers and neuroendocrine markers.
Reference Gallery:
Merkel cell carcinoma. Nodule on the upper lip.
Merkel cell carcinoma. The tumour cells display a fine stippled chromatin pattern. There is nuclear moulding.
Merkel cell carcinoma. Involvement of the dermis and subcutis.
Merkel cell carcinoma. The tumour cells display a pale salt-and-pepper chromatin pattern; there is focal rosette-like arrangement of the nuclei; several mitotic figures are present.
Merkel cell carcinoma. The tumour cells are uniformly immunoreactive with CM2B4 (a monoclonal antibody to the MCPyV large T antigen).
Merkel cell carcinoma. The tumour cells display a trabecular architecture.
Merkel cell carcinoma. Combined neuroendocrine and invasive squamous cell carcinoma. A minor component of the tumour shows squamous differentiation.
Merkel cell carcinoma. Higher magnification shows nuclear labelling of the tumour cells with CM2B4.
Merkel cell carcinoma. The tumour cells are immunoreactive for CK20 in a perinuclear dot-like pattern.
Merkel cell carcinoma. Malignant blue cell tumour in dermis and subcutis.
Merkel cell carcinoma. Epidermotropic Merkel cell carcinoma. Tumour cells are present in both the epidermis and dermis.

Q: The tumor cells in Merkel Cell Carcinoma are characteristically immunoreactive with CM2B4, a monoclonal antibody directed against the [...].
Merkel cell carcinoma. The tumour cells are uniformly immunoreactive with CM2B4 (a monoclonal antibody to the MCPyV large T antigen).
Merkel cell carcinoma. Higher magnification shows nuclear labelling of the tumour cells with CM2B4.
A: MCPyV large T antigen
Back Extra: Merkel Cell Carcinoma
- Clinical: Merkel cell carcinoma typically appears as a rapidly growing flesh-colored or violaceous nodule or plaque, most commonly on sun-damaged skin, especially the head and neck, extremities, and trunk.
- Micro: The tumour cells display a fine stippled (salt-and-pepper) chromatin pattern, nuclear moulding, and numerous mitotic figures. They often form large or small aggregates and may display a trabecular growth pattern.
- Ancillary: Immunohistochemically, tumour cells are uniformly immunoreactive with CM2B4 (MCPyV large T antigen) and CK20 in a perinuclear dot-like pattern. They also express epithelial markers and neuroendocrine markers.
Reference Gallery:
Merkel cell carcinoma. Nodule on the upper lip.
Merkel cell carcinoma. The tumour cells display a fine stippled chromatin pattern. There is nuclear moulding.
Merkel cell carcinoma. Involvement of the dermis and subcutis.
Merkel cell carcinoma. The tumour cells display a pale salt-and-pepper chromatin pattern; there is focal rosette-like arrangement of the nuclei; several mitotic figures are present.
Merkel cell carcinoma. The tumour cells are uniformly immunoreactive with CM2B4 (a monoclonal antibody to the MCPyV large T antigen).
Merkel cell carcinoma. The tumour cells display a trabecular architecture.
Merkel cell carcinoma. Combined neuroendocrine and invasive squamous cell carcinoma. A minor component of the tumour shows squamous differentiation.
Merkel cell carcinoma. Higher magnification shows nuclear labelling of the tumour cells with CM2B4.
Merkel cell carcinoma. The tumour cells are immunoreactive for CK20 in a perinuclear dot-like pattern.
Merkel cell carcinoma. Malignant blue cell tumour in dermis and subcutis.
Merkel cell carcinoma. Epidermotropic Merkel cell carcinoma. Tumour cells are present in both the epidermis and dermis.

Q: A classic cutaneous Neurofibroma is an unencapsulated dermal tumor characterized by spindle cells with thin, [...] nuclei, delicate collagen strands, and conspicuous mast cells.
Cutaneous neurofibroma. A well-circumscribed but unencapsulated, pale eosinophilic tumour centred in the dermis.
Cutaneous neurofibroma. Spindle cells with thin, wavy, hyperchromatic nuclei and delicate, pale eosinophilic cytoplasmic processes; these spindle cells are embedded in a matrix of thin strands of collagen and interstitial mucin, with an associated infiltrate of small mature lymphocytes, histiocytes, and conspicuous mast cells.
A: wavy
Back Extra: Neurofibroma
- Clinical: Neurofibromas are often solitary, slow-growing, painless, soft, skin-coloured papules or nodules. Plexiform neurofibromas are congenital, irregular, tortuous, multinodular masses, typically affecting children or young adults.
- Micro: Neurofibromas are unencapsulated tumours composed of spindle cells, collagen fibres, lymphocytes, and mast cells. They may show a myxoid, sclerotic, or lipomatous pattern.
- Ancillary: Some cells in neurofibromas are positive for S100 and SOX10. CD34-positive perineurial fibroblasts anastomose around Schwann cells, forming a characteristic 'fingerprint' pattern.
Reference Gallery:
Cutaneous neurofibroma. A well-circumscribed but unencapsulated, pale eosinophilic tumour centred in the dermis.
Diffuse neurofibroma. Pale eosinophilic tumour infiltrating the dermis (without effacing endogenous structures) and extending into the subcutis.
Diffuse neurofibroma. High-magnification view of tumour cells insinuating within subcutaneous adipose tissue.
Plexiform neurofibroma. Serpiginous, expanded nerve bundles infiltrated by tumour.
Cutaneous neurofibroma. Spindle cells in a matrix composed of strands of collagen.
Mixed-pattern (plexiform and diffuse) neurofibroma. Tortuous nerve bundles expanded by tumour with spillage into the surrounding tissue, without effacement of architecture; note the preservation of glandular structures.
Cutaneous neurofibroma. Spindle cells with thin, wavy, hyperchromatic nuclei and delicate, pale eosinophilic cytoplasmic processes; these spindle cells are embedded in a matrix of thin strands of collagen and interstitial mucin, with an associated infiltrate of small mature lymphocytes, histiocytes, and conspicuous mast cells.

Q: The plexiform variant of Neurofibroma is classically characterized histologically by tortuous, serpiginous, and expanded [...] infiltrated by tumor.
Plexiform neurofibroma. Serpiginous, expanded nerve bundles infiltrated by tumour.
Mixed-pattern (plexiform and diffuse) neurofibroma. Tortuous nerve bundles expanded by tumour with spillage into the surrounding tissue, without effacement of architecture; note the preservation of glandular structures.
A: nerve bundles
Back Extra: Neurofibroma
- Clinical: Neurofibromas are often solitary, slow-growing, painless, soft, skin-coloured papules or nodules. Plexiform neurofibromas are congenital, irregular, tortuous, multinodular masses, typically affecting children or young adults.
- Micro: Neurofibromas are unencapsulated tumours composed of spindle cells, collagen fibres, lymphocytes, and mast cells. They may show a myxoid, sclerotic, or lipomatous pattern.
- Ancillary: Some cells in neurofibromas are positive for S100 and SOX10. CD34-positive perineurial fibroblasts anastomose around Schwann cells, forming a characteristic 'fingerprint' pattern.
Reference Gallery:
Cutaneous neurofibroma. A well-circumscribed but unencapsulated, pale eosinophilic tumour centred in the dermis.
Diffuse neurofibroma. Pale eosinophilic tumour infiltrating the dermis (without effacing endogenous structures) and extending into the subcutis.
Diffuse neurofibroma. High-magnification view of tumour cells insinuating within subcutaneous adipose tissue.
Plexiform neurofibroma. Serpiginous, expanded nerve bundles infiltrated by tumour.
Cutaneous neurofibroma. Spindle cells in a matrix composed of strands of collagen.
Mixed-pattern (plexiform and diffuse) neurofibroma. Tortuous nerve bundles expanded by tumour with spillage into the surrounding tissue, without effacement of architecture; note the preservation of glandular structures.
Cutaneous neurofibroma. Spindle cells with thin, wavy, hyperchromatic nuclei and delicate, pale eosinophilic cytoplasmic processes; these spindle cells are embedded in a matrix of thin strands of collagen and interstitial mucin, with an associated infiltrate of small mature lymphocytes, histiocytes, and conspicuous mast cells.

Q: The diffuse variant of Neurofibroma features tumor cells that broadly infiltrate the dermis and extend into the subcutis, characteristically insinuating within the subcutaneous [...].
Diffuse neurofibroma. Pale eosinophilic tumour infiltrating the dermis (without effacing endogenous structures) and extending into the subcutis.
Diffuse neurofibroma. High-magnification view of tumour cells insinuating within subcutaneous adipose tissue.
A: adipose tissue
Back Extra: Neurofibroma
- Clinical: Neurofibromas are often solitary, slow-growing, painless, soft, skin-coloured papules or nodules. Plexiform neurofibromas are congenital, irregular, tortuous, multinodular masses, typically affecting children or young adults.
- Micro: Neurofibromas are unencapsulated tumours composed of spindle cells, collagen fibres, lymphocytes, and mast cells. They may show a myxoid, sclerotic, or lipomatous pattern.
- Ancillary: Some cells in neurofibromas are positive for S100 and SOX10. CD34-positive perineurial fibroblasts anastomose around Schwann cells, forming a characteristic 'fingerprint' pattern.
Reference Gallery:
Cutaneous neurofibroma. A well-circumscribed but unencapsulated, pale eosinophilic tumour centred in the dermis.
Diffuse neurofibroma. Pale eosinophilic tumour infiltrating the dermis (without effacing endogenous structures) and extending into the subcutis.
Diffuse neurofibroma. High-magnification view of tumour cells insinuating within subcutaneous adipose tissue.
Plexiform neurofibroma. Serpiginous, expanded nerve bundles infiltrated by tumour.
Cutaneous neurofibroma. Spindle cells in a matrix composed of strands of collagen.
Mixed-pattern (plexiform and diffuse) neurofibroma. Tortuous nerve bundles expanded by tumour with spillage into the surrounding tissue, without effacement of architecture; note the preservation of glandular structures.
Cutaneous neurofibroma. Spindle cells with thin, wavy, hyperchromatic nuclei and delicate, pale eosinophilic cytoplasmic processes; these spindle cells are embedded in a matrix of thin strands of collagen and interstitial mucin, with an associated infiltrate of small mature lymphocytes, histiocytes, and conspicuous mast cells.

Q: Microscopically, a non-neural granular cell tumor often presents as a polypoid lesion with an epithelial collarette and large, oval cells containing abundant coarse [...].
Non-neural granular cell tumour. The lesions are often polypoid, with an epithelial collarette.
Non-neural granular cell tumour. Note the large oval cells with abundant cytoplasmic eosinophilic granules.
A: eosinophilic granules
Back Extra: Non-neural granular cell tumour
- Clinical: Non-neural granular cell tumours typically present as non-ulcerated papules or nodules, commonly on the back or widely distributed on the torso, limbs, and face.
- Micro: The tumour cells are large and oval with coarse eosinophilic granules, often forming sheets and showing epithelial collarettes.
- Ancillary: The cells are usually positive for CD68 and CD63 but negative for S100, desmin, SMA, and cytokeratin.
Reference Gallery:
Non-neural granular cell tumour. The lesions are often polypoid, with an epithelial collarette.
Non-neural granular cell tumour. Note the large oval cells with abundant cytoplasmic eosinophilic granules.
Non-neural granular cell tumour. Cytological atypia and pleomorphism may be encountered, but they do not correlate with a more aggressive course; note the pustulo-ovoid bodies of Milian in the right side of the field.

Q: In a non-neural granular cell tumor, the presence of cytological atypia and [...] does not correlate with a more aggressive clinical course.
Non-neural granular cell tumour. Cytological atypia and pleomorphism may be encountered, but they do not correlate with a more aggressive course; note the pustulo-ovoid bodies of Milian in the right side of the field.
A: pustulo-ovoid bodies of Milian
Back Extra: Non-neural granular cell tumour
- Clinical: Non-neural granular cell tumours typically present as non-ulcerated papules or nodules, commonly on the back or widely distributed on the torso, limbs, and face.
- Micro: The tumour cells are large and oval with coarse eosinophilic granules, often forming sheets and showing epithelial collarettes.
- Ancillary: The cells are usually positive for CD68 and CD63 but negative for S100, desmin, SMA, and cytokeratin.
Reference Gallery:
Non-neural granular cell tumour. The lesions are often polypoid, with an epithelial collarette.
Non-neural granular cell tumour. Note the large oval cells with abundant cytoplasmic eosinophilic granules.
Non-neural granular cell tumour. Cytological atypia and pleomorphism may be encountered, but they do not correlate with a more aggressive course; note the pustulo-ovoid bodies of Milian in the right side of the field.

Q: Histologically, Solitary Circumscribed Neuroma presents as a circumscribed dermal tumor composed of bland spindle cell fascicles that frequently exhibit characteristic [...] at the tumor-stroma interface.
Solitary circumscribed neuroma. A circumscribed dermal tumour is composed of fascicles of bland spindle cells without prominent palisading. Artefactual clefting is a characteristic feature.
A: artifactual clefting
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary circumscribed neuroma typically presents as a small, solitary, asymptomatic, firm, skin-coloured papule, most commonly on the face.
- Micro: The tumour is composed of fascicles of bland spindled cells within a dermal nodule, often with artefactual clefting at the tumour-stroma interface.
- Ancillary: Schwann cells in the tumour are strongly positive for S100, and CD34 staining shows a characteristic chicken-wire pattern.
Reference Gallery:
Solitary circumscribed neuroma. A circumscribed dermal tumour is composed of fascicles of bland spindle cells without prominent palisading. Artefactual clefting is a characteristic feature.
Solitary circumscribed neuroma. Schwann cells within the tumour stain diffusely positive for S100.
Solitary circumscribed neuroma. A variable number of axons are distributed throughout the tumour, as highlighted by NFP staining.
Solitary circumscribed neuroma. EMA is expressed by perineural cells in the capsule.
Solitary circumscribed neuroma. Solitary circumscribed neuroma shows a chicken-wire pattern of staining for CD34.

Q: In Solitary Circumscribed Neuroma, CD34 immunohistochemistry characteristically demonstrates a distinct [...] staining pattern throughout the tumor.
Solitary circumscribed neuroma. Solitary circumscribed neuroma shows a chicken-wire pattern of staining for CD34.
A: chicken-wire
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary circumscribed neuroma typically presents as a small, solitary, asymptomatic, firm, skin-coloured papule, most commonly on the face.
- Micro: The tumour is composed of fascicles of bland spindled cells within a dermal nodule, often with artefactual clefting at the tumour-stroma interface.
- Ancillary: Schwann cells in the tumour are strongly positive for S100, and CD34 staining shows a characteristic chicken-wire pattern.
Reference Gallery:
Solitary circumscribed neuroma. A circumscribed dermal tumour is composed of fascicles of bland spindle cells without prominent palisading. Artefactual clefting is a characteristic feature.
Solitary circumscribed neuroma. Schwann cells within the tumour stain diffusely positive for S100.
Solitary circumscribed neuroma. A variable number of axons are distributed throughout the tumour, as highlighted by NFP staining.
Solitary circumscribed neuroma. EMA is expressed by perineural cells in the capsule.
Solitary circumscribed neuroma. Solitary circumscribed neuroma shows a chicken-wire pattern of staining for CD34.

Q: Immunohistochemistry in Solitary Circumscribed Neuroma highlights its distinct components: axons are marked by NFP, the surrounding capsule expresses EMA, and the admixed Schwann cells are strongly and diffusely positive for [...].
Solitary circumscribed neuroma. Schwann cells within the tumour stain diffusely positive for S100.
Solitary circumscribed neuroma. A variable number of axons are distributed throughout the tumour, as highlighted by NFP staining.
Solitary circumscribed neuroma. EMA is expressed by perineural cells in the capsule.
A: S100
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary circumscribed neuroma typically presents as a small, solitary, asymptomatic, firm, skin-coloured papule, most commonly on the face.
- Micro: The tumour is composed of fascicles of bland spindled cells within a dermal nodule, often with artefactual clefting at the tumour-stroma interface.
- Ancillary: Schwann cells in the tumour are strongly positive for S100, and CD34 staining shows a characteristic chicken-wire pattern.
Reference Gallery:
Solitary circumscribed neuroma. A circumscribed dermal tumour is composed of fascicles of bland spindle cells without prominent palisading. Artefactual clefting is a characteristic feature.
Solitary circumscribed neuroma. Schwann cells within the tumour stain diffusely positive for S100.
Solitary circumscribed neuroma. A variable number of axons are distributed throughout the tumour, as highlighted by NFP staining.
Solitary circumscribed neuroma. EMA is expressed by perineural cells in the capsule.
Solitary circumscribed neuroma. Solitary circumscribed neuroma shows a chicken-wire pattern of staining for CD34.

Q: Microscopically, Perineurioma features a storiform to fascicular growth pattern within a collagenous to myxoid stroma, comprising monomorphic spindle cells with characteristic [...] nuclei.
Cutaneous perineurioma. A well-demarcated, acral pop-out lesion with fine collagen fibres, storiform to fascicular, in a lamellar arrangement, and moderate perivascular whorls, with interspersed monomorphic slender spindle cells.
Perineurioma, soft tissue. A perineurioma with a fascicular, lamellar and moderately whorled, more dense character, with fine collagen fibres in the lower-right, while the upper-left is storiform to whorled and looser to myxoid, with beginning reticular arrangement. Note the monomorphic, slender spindle cells with wavy tapering nuclei and delicate bipolar cytoplasmic extensions.
A: wavy, tapering
Back Extra: Perineurioma
- Clinical: Perineuriomas typically appear as well-circumscribed, painless, skin-coloured papules, nodules, or tumours, most commonly in the subcutaneous tissue of middle-aged adults.
- Micro: Perineuriomas show a storiform to fascicular growth pattern with a collagenous to myxoid stroma, and monomorphic spindle cells with wavy, tapering nuclei.
- Ancillary: EMA is positive in perineuriomas, from weak and focal to strong and diffuse, while S100, SOX10, and GFAP are negative.
Reference Gallery:
Cutaneous perineurioma. A well-demarcated, acral pop-out lesion with fine collagen fibres, storiform to fascicular, in a lamellar arrangement, and moderate perivascular whorls, with interspersed monomorphic slender spindle cells.
Perineurioma. EMA immunoreactivity of slender spindle cells with wavy tapering nuclei and delicate bipolar to dendritic reactivity. Note that this reactivity can be quite variable within a given lesion, as well as from lesion to lesion.
Perineurioma, cutaneous sclerotic. Scanning magnification of a well-demarcated, acral lesion with homogeneous, faintly eosinophilic, cell-pure character contrasting with vascular structures.
Sclerotic cutaneous perineurioma. A well-demarcated lesion with fine collagen fibres, storiform, lamellar, and prominently whorled with central sclerosis. There are interspersed monomorphic, small, round/oval to spindle cells.
Cutaneous perineurioma, vascular-rich pattern. A well-demarcated, acral lesion with fine collagen fibres, fascicular and lamellar, and prominent small round dilated to prominently elongated vessels. There are interspersed monomorphic round/oval to slender spindle cells.
Subcutaneous perineurioma. A well-demarcated lesion with fibrosclerotic collagen, lamellar arrangement, and prominent perivascular whorls. There are interspersed monomorphic, inconspicuous, round/oval to spindle cells.
Subcutaneous perineurioma. A well-demarcated lesion with fibrosclerotic collagen, lamellar arrangement, and prominent perivascular whorls, with interspersed monomorphic, inconspicuous, mostly round to oval perineurial cells.
Perineurioma, soft tissue. A perineurioma with a fascicular, lamellar and moderately whorled, more dense character, with fine collagen fibres in the lower-right, while the upper-left is storiform to whorled and looser to myxoid, with beginning reticular arrangement. Note the monomorphic, slender spindle cells with wavy tapering nuclei and delicate bipolar cytoplasmic extensions.
Reticular perineurioma. Myxoid stroma and reticular arrangement of spindle cells.
Soft tissue perineurioma. Tumour with variably myxoid to collagenous stroma, mimicking low-grade fibromyxoid sarcoma.

Q: Immunohistochemically, the neoplastic spindle cells in a Perineurioma are classically positive for [...], while typically remaining negative for S100, SOX10, and GFAP.
Perineurioma. EMA immunoreactivity of slender spindle cells with wavy tapering nuclei and delicate bipolar to dendritic reactivity. Note that this reactivity can be quite variable within a given lesion, as well as from lesion to lesion.
A: EMA
Back Extra: Perineurioma
- Clinical: Perineuriomas typically appear as well-circumscribed, painless, skin-coloured papules, nodules, or tumours, most commonly in the subcutaneous tissue of middle-aged adults.
- Micro: Perineuriomas show a storiform to fascicular growth pattern with a collagenous to myxoid stroma, and monomorphic spindle cells with wavy, tapering nuclei.
- Ancillary: EMA is positive in perineuriomas, from weak and focal to strong and diffuse, while S100, SOX10, and GFAP are negative.
Reference Gallery:
Cutaneous perineurioma. A well-demarcated, acral pop-out lesion with fine collagen fibres, storiform to fascicular, in a lamellar arrangement, and moderate perivascular whorls, with interspersed monomorphic slender spindle cells.
Perineurioma. EMA immunoreactivity of slender spindle cells with wavy tapering nuclei and delicate bipolar to dendritic reactivity. Note that this reactivity can be quite variable within a given lesion, as well as from lesion to lesion.
Perineurioma, cutaneous sclerotic. Scanning magnification of a well-demarcated, acral lesion with homogeneous, faintly eosinophilic, cell-pure character contrasting with vascular structures.
Sclerotic cutaneous perineurioma. A well-demarcated lesion with fine collagen fibres, storiform, lamellar, and prominently whorled with central sclerosis. There are interspersed monomorphic, small, round/oval to spindle cells.
Cutaneous perineurioma, vascular-rich pattern. A well-demarcated, acral lesion with fine collagen fibres, fascicular and lamellar, and prominent small round dilated to prominently elongated vessels. There are interspersed monomorphic round/oval to slender spindle cells.
Subcutaneous perineurioma. A well-demarcated lesion with fibrosclerotic collagen, lamellar arrangement, and prominent perivascular whorls. There are interspersed monomorphic, inconspicuous, round/oval to spindle cells.
Subcutaneous perineurioma. A well-demarcated lesion with fibrosclerotic collagen, lamellar arrangement, and prominent perivascular whorls, with interspersed monomorphic, inconspicuous, mostly round to oval perineurial cells.
Perineurioma, soft tissue. A perineurioma with a fascicular, lamellar and moderately whorled, more dense character, with fine collagen fibres in the lower-right, while the upper-left is storiform to whorled and looser to myxoid, with beginning reticular arrangement. Note the monomorphic, slender spindle cells with wavy tapering nuclei and delicate bipolar cytoplasmic extensions.
Reticular perineurioma. Myxoid stroma and reticular arrangement of spindle cells.
Soft tissue perineurioma. Tumour with variably myxoid to collagenous stroma, mimicking low-grade fibromyxoid sarcoma.

Q: Architecturally, the spindle cells in Perineurioma frequently display a lamellar arrangement and characteristically form prominent [...].
Subcutaneous perineurioma. A well-demarcated lesion with fibrosclerotic collagen, lamellar arrangement, and prominent perivascular whorls. There are interspersed monomorphic, inconspicuous, round/oval to spindle cells.
Subcutaneous perineurioma. A well-demarcated lesion with fibrosclerotic collagen, lamellar arrangement, and prominent perivascular whorls, with interspersed monomorphic, inconspicuous, mostly round to oval perineurial cells.
A: perivascular whorls
Back Extra: Perineurioma
- Clinical: Perineuriomas typically appear as well-circumscribed, painless, skin-coloured papules, nodules, or tumours, most commonly in the subcutaneous tissue of middle-aged adults.
- Micro: Perineuriomas show a storiform to fascicular growth pattern with a collagenous to myxoid stroma, and monomorphic spindle cells with wavy, tapering nuclei.
- Ancillary: EMA is positive in perineuriomas, from weak and focal to strong and diffuse, while S100, SOX10, and GFAP are negative.
Reference Gallery:
Cutaneous perineurioma. A well-demarcated, acral pop-out lesion with fine collagen fibres, storiform to fascicular, in a lamellar arrangement, and moderate perivascular whorls, with interspersed monomorphic slender spindle cells.
Perineurioma. EMA immunoreactivity of slender spindle cells with wavy tapering nuclei and delicate bipolar to dendritic reactivity. Note that this reactivity can be quite variable within a given lesion, as well as from lesion to lesion.
Perineurioma, cutaneous sclerotic. Scanning magnification of a well-demarcated, acral lesion with homogeneous, faintly eosinophilic, cell-pure character contrasting with vascular structures.
Sclerotic cutaneous perineurioma. A well-demarcated lesion with fine collagen fibres, storiform, lamellar, and prominently whorled with central sclerosis. There are interspersed monomorphic, small, round/oval to spindle cells.
Cutaneous perineurioma, vascular-rich pattern. A well-demarcated, acral lesion with fine collagen fibres, fascicular and lamellar, and prominent small round dilated to prominently elongated vessels. There are interspersed monomorphic round/oval to slender spindle cells.
Subcutaneous perineurioma. A well-demarcated lesion with fibrosclerotic collagen, lamellar arrangement, and prominent perivascular whorls. There are interspersed monomorphic, inconspicuous, round/oval to spindle cells.
Subcutaneous perineurioma. A well-demarcated lesion with fibrosclerotic collagen, lamellar arrangement, and prominent perivascular whorls, with interspersed monomorphic, inconspicuous, mostly round to oval perineurial cells.
Perineurioma, soft tissue. A perineurioma with a fascicular, lamellar and moderately whorled, more dense character, with fine collagen fibres in the lower-right, while the upper-left is storiform to whorled and looser to myxoid, with beginning reticular arrangement. Note the monomorphic, slender spindle cells with wavy tapering nuclei and delicate bipolar cytoplasmic extensions.
Reticular perineurioma. Myxoid stroma and reticular arrangement of spindle cells.
Soft tissue perineurioma. Tumour with variably myxoid to collagenous stroma, mimicking low-grade fibromyxoid sarcoma.

Q: The hallmark histologic feature of a Schwannoma is an alternating pattern of hypocellular myxoid Antoni B areas and hypercellular Antoni A areas that frequently contain palisading structures called [...].
Schwannoma. An Antoni A area demonstrating palisading Verocay bodies.
Schwannoma. An Antoni B area demonstrating a hypocellular myxoid region adjacent to Antoni A changes.
A: Verocay bodies
Back Extra: Schwannoma
- Clinical: Schwannomas are typically solitary, slow-growing, and can be painful, often found in the extremities, head and neck, and trunk.
- Micro: Characterized by alternating Antoni A (cellular, with Verocay bodies) and Antoni B (hypocellular, myxoid) areas.
- Ancillary: Strong positivity for S100 and SOX10, and somatic loss-of-function mutations in NF2.
Reference Gallery:
Schwannoma. An Antoni A area demonstrating palisading Verocay bodies.
Schwannoma. An Antoni B area demonstrating a hypocellular myxoid region adjacent to Antoni A changes.
Cellular schwannoma. Increased cellularity with fascicular architecture.
Neuroblastoma-like schwannoma. A characteristic pseudorosette.
Plexiform schwannoma. Multiple schwannoma nodules in the dermis.
Epithelioid schwannoma. Epithelioid tumour cells.

Q: Unlike a conventional Schwannoma, the [...] variant of Schwannoma exhibits increased cellularity with a predominantly fascicular architecture and typically lacks well-developed Verocay bodies.
Cellular schwannoma. Increased cellularity with fascicular architecture.
A: cellular
Back Extra: Schwannoma
- Clinical: Schwannomas are typically solitary, slow-growing, and can be painful, often found in the extremities, head and neck, and trunk.
- Micro: Characterized by alternating Antoni A (cellular, with Verocay bodies) and Antoni B (hypocellular, myxoid) areas.
- Ancillary: Strong positivity for S100 and SOX10, and somatic loss-of-function mutations in NF2.
Reference Gallery:
Schwannoma. An Antoni A area demonstrating palisading Verocay bodies.
Schwannoma. An Antoni B area demonstrating a hypocellular myxoid region adjacent to Antoni A changes.
Cellular schwannoma. Increased cellularity with fascicular architecture.
Neuroblastoma-like schwannoma. A characteristic pseudorosette.
Plexiform schwannoma. Multiple schwannoma nodules in the dermis.
Epithelioid schwannoma. Epithelioid tumour cells.

Q: The [...] variant of Schwannoma typically presents as multiple interconnected tumor nodules in the dermis or subcutis, expanding along a nerve plexus.
Plexiform schwannoma. Multiple schwannoma nodules in the dermis.
A: plexiform
Back Extra: Schwannoma
- Clinical: Schwannomas are typically solitary, slow-growing, and can be painful, often found in the extremities, head and neck, and trunk.
- Micro: Characterized by alternating Antoni A (cellular, with Verocay bodies) and Antoni B (hypocellular, myxoid) areas.
- Ancillary: Strong positivity for S100 and SOX10, and somatic loss-of-function mutations in NF2.
Reference Gallery:
Schwannoma. An Antoni A area demonstrating palisading Verocay bodies.
Schwannoma. An Antoni B area demonstrating a hypocellular myxoid region adjacent to Antoni A changes.
Cellular schwannoma. Increased cellularity with fascicular architecture.
Neuroblastoma-like schwannoma. A characteristic pseudorosette.
Plexiform schwannoma. Multiple schwannoma nodules in the dermis.
Epithelioid schwannoma. Epithelioid tumour cells.

Q: Histologically, Ewing Sarcoma tumors are classically composed of sheets of mitotically active, uniform [...] with indistinct cell borders and finely stippled chromatin.
Cutaneous Ewing sarcoma. Dermal tumour composed of small round blue cells with high N:C ratio.
Cutaneous Ewing sarcoma. Small round blue cells with nuclei with finely stippled chromatin and inconspicuous nucleoli, scant clear to eosinophilic cytoplasm, and indistinct cytoplasmic borders. Note the mitoses.
A: small round blue cells
Back Extra: Ewing Sarcoma
- Clinical: Ewing sarcoma manifests as dermal or subcutaneous nodules that may be painful, polypoid, and/or ulcerated. Median tumour size is 23 mm (range: 5–120 mm).
- Micro: Tumours are composed of sheets of mitotically active, uniform small blue round cells with indistinct cell borders and round nuclei with fine stippled chromatin.
- Ancillary: Membranous CD99 immunoreactivity is a highly sensitive but nonspecific finding. Molecular confirmation with FET::ETS fusions is required for diagnosis.
Reference Gallery:
Cutaneous Ewing sarcoma. Dermal tumour composed of small round blue cells with high N:C ratio.
Cutaneous Ewing sarcoma. Small round blue cells with nuclei with finely stippled chromatin and inconspicuous nucleoli, scant clear to eosinophilic cytoplasm, and indistinct cytoplasmic borders. Note the mitoses.
Cutaneous Ewing sarcoma. Ewing sarcoma typically demonstrates strong and diffuse membranous CD99 immunoreactivity.

Q: A highly sensitive immunohistochemical finding in Ewing Sarcoma is strong and diffuse membranous staining for [...].
Cutaneous Ewing sarcoma. Ewing sarcoma typically demonstrates strong and diffuse membranous CD99 immunoreactivity.
A: CD99
Back Extra: Ewing Sarcoma
- Clinical: Ewing sarcoma manifests as dermal or subcutaneous nodules that may be painful, polypoid, and/or ulcerated. Median tumour size is 23 mm (range: 5–120 mm).
- Micro: Tumours are composed of sheets of mitotically active, uniform small blue round cells with indistinct cell borders and round nuclei with fine stippled chromatin.
- Ancillary: Membranous CD99 immunoreactivity is a highly sensitive but nonspecific finding. Molecular confirmation with FET::ETS fusions is required for diagnosis.
Reference Gallery:
Cutaneous Ewing sarcoma. Dermal tumour composed of small round blue cells with high N:C ratio.
Cutaneous Ewing sarcoma. Small round blue cells with nuclei with finely stippled chromatin and inconspicuous nucleoli, scant clear to eosinophilic cytoplasm, and indistinct cytoplasmic borders. Note the mitoses.
Cutaneous Ewing sarcoma. Ewing sarcoma typically demonstrates strong and diffuse membranous CD99 immunoreactivity.

Q: A classic histologic pattern of NTRK-rearranged spindle cell neoplasm is a [...]-like appearance, featuring fibrous septa and increased spindled cells.
NTRK-rearranged spindle cell neoplasm. Superficial tumour with TPR::NTRK1 fusion, resembling lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Superficial tumour with TPR::NTRK1 fusion, resembling lipofibromatosis.
A: lipofibromatosis
Back Extra: NTRK-rearranged spindle cell neoplasm
- Clinical: NTRK-rearranged spindle cell neoplasms present as palpable masses, typically 10–60 mm in diameter, and are most frequently seen in the paediatric population but can occur at any age.
- Micro: These neoplasms can exhibit a lipofibromatosis-like pattern with fibrous septa and increased spindled cells, or a more cellular appearance with sheets of spindled to ovoid cells in a myxoid background.
- Ancillary: Tumours often show diffuse pan-TRK expression and may coexpress CD34, S100, or SMA. Molecular genetic testing is essential for confirming the diagnosis.
Reference Gallery:
NTRK-rearranged spindle cell neoplasm. Superficial tumour with TPR::NTRK1 fusion, resembling lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Superficial tumour with TPR::NTRK1 fusion, resembling lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Superficial tumour with TPR::NTRK1 fusion, resembling lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Hybrid tumour with TPR::NTRK1 fusion; an area with increased cellularity reminiscent of low-grade malignant peripheral nerve sheath tumour.
NTRK-rearranged spindle cell neoplasm. Tumour with TPM3::NTRK1 fusion; an area resembling high-grade spindle cell sarcoma.
NTRK-rearranged spindle cell neoplasm. Tumour with TPM3::NTRK1 fusion and diffuse immunoreactivity for pan-TRK.

Q: For the ancillary workup of NTRK-rearranged spindle cell neoplasm, tumors characteristically demonstrate diffuse immunohistochemical expression of [...].
NTRK-rearranged spindle cell neoplasm. Tumour with TPM3::NTRK1 fusion and diffuse immunoreactivity for pan-TRK.
A: pan-TRK
Back Extra: NTRK-rearranged spindle cell neoplasm
- Clinical: NTRK-rearranged spindle cell neoplasms present as palpable masses, typically 10–60 mm in diameter, and are most frequently seen in the paediatric population but can occur at any age.
- Micro: These neoplasms can exhibit a lipofibromatosis-like pattern with fibrous septa and increased spindled cells, or a more cellular appearance with sheets of spindled to ovoid cells in a myxoid background.
- Ancillary: Tumours often show diffuse pan-TRK expression and may coexpress CD34, S100, or SMA. Molecular genetic testing is essential for confirming the diagnosis.
Reference Gallery:
NTRK-rearranged spindle cell neoplasm. Superficial tumour with TPR::NTRK1 fusion, resembling lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Superficial tumour with TPR::NTRK1 fusion, resembling lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Superficial tumour with TPR::NTRK1 fusion, resembling lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Hybrid tumour with TPR::NTRK1 fusion; an area with increased cellularity reminiscent of low-grade malignant peripheral nerve sheath tumour.
NTRK-rearranged spindle cell neoplasm. Tumour with TPM3::NTRK1 fusion; an area resembling high-grade spindle cell sarcoma.
NTRK-rearranged spindle cell neoplasm. Tumour with TPM3::NTRK1 fusion and diffuse immunoreactivity for pan-TRK.

Q: Acquired Elastotic Haemangioma features a superficial dermal proliferation of small blood vessels that are lined by a single layer of endothelial cells and characteristically surrounded by an outer layer of [...].
Acquired elastotic haemangioma. Small blood vessels lined by a single layer of endothelial cells surrounded by a layer of pericytes and associated with solar elastosis.
A: pericytes
Back Extra: Acquired Elastotic Haemangioma
- Clinical: Asymptomatic, small papule or plaque in sun-exposed skin, more common in middle-aged and elderly adults with a slight female predilection.
- Micro: Band-like proliferation of capillaries in the upper reticular dermis, with a layer of pericytes and associated solar elastosis.
- Ancillary: Not relevant for diagnosis.
Reference Gallery:
Acquired elastotic haemangioma. Plaque-like superficial dermal proliferation of small vascular channels in the background of solar elastosis.
Acquired elastotic haemangioma. Small blood vessels lined by a single layer of endothelial cells surrounded by a layer of pericytes and associated with solar elastosis.

Q: [...] typically presents as an asymptomatic small papule or plaque on sun-exposed skin and microscopically features a band-like proliferation of capillaries within a prominent background of solar elastosis.
Acquired elastotic haemangioma. Plaque-like superficial dermal proliferation of small vascular channels in the background of solar elastosis.
Acquired elastotic haemangioma. Small blood vessels lined by a single layer of endothelial cells surrounded by a layer of pericytes and associated with solar elastosis.
A: Acquired Elastotic Haemangioma
Back Extra: Acquired Elastotic Haemangioma
- Clinical: Asymptomatic, small papule or plaque in sun-exposed skin, more common in middle-aged and elderly adults with a slight female predilection.
- Micro: Band-like proliferation of capillaries in the upper reticular dermis, with a layer of pericytes and associated solar elastosis.
- Ancillary: Not relevant for diagnosis.
Reference Gallery:
Acquired elastotic haemangioma. Plaque-like superficial dermal proliferation of small vascular channels in the background of solar elastosis.
Acquired elastotic haemangioma. Small blood vessels lined by a single layer of endothelial cells surrounded by a layer of pericytes and associated with solar elastosis.

Q: A hallmark histologic feature of Angiokeratoma is the presence of dilated, congested vascular channels located specifically within the [...].
Angiokeratoma. Congested and dilated vascular channels lined by a single flattened layer of endothelial cells.
A: papillary dermis
Back Extra: Angiokeratoma
- Clinical: Patients with Angiokeratoma corporis diffusum (ACD) present with numerous asymptomatic pinpoint papules, while Angiokeratoma of Fordyce (AF) and Angiokeratoma of Mibelli (AM) present with single or multiple small red keratotic papules.
- Micro: Angiokeratoma shows dilated, congested vascular channels in the papillary dermis, often associated with overlying epidermal changes such as acanthosis and hyperkeratosis.
- Ancillary: Ancillary studies are not relevant in the diagnosis of Angiokeratoma.
Reference Gallery:
Angiokeratoma. Congested and dilated vascular channels lined by a single flattened layer of endothelial cells.
Angiokeratoma. Low-power image demonstrating epidermal changes of angiokeratoma.

Q: In Angiokeratoma, the superficial vascular proliferation is characteristically accompanied by overlying epidermal changes, most notably [...].
Angiokeratoma. Low-power image demonstrating epidermal changes of angiokeratoma.
A: acanthosis and hyperkeratosis
Back Extra: Angiokeratoma
- Clinical: Patients with Angiokeratoma corporis diffusum (ACD) present with numerous asymptomatic pinpoint papules, while Angiokeratoma of Fordyce (AF) and Angiokeratoma of Mibelli (AM) present with single or multiple small red keratotic papules.
- Micro: Angiokeratoma shows dilated, congested vascular channels in the papillary dermis, often associated with overlying epidermal changes such as acanthosis and hyperkeratosis.
- Ancillary: Ancillary studies are not relevant in the diagnosis of Angiokeratoma.
Reference Gallery:
Angiokeratoma. Congested and dilated vascular channels lined by a single flattened layer of endothelial cells.
Angiokeratoma. Low-power image demonstrating epidermal changes of angiokeratoma.

Q: A clinical presentation of a violaceous plaque on the sun-damaged scalp of an elderly patient, paired with a histology of anastomosing vessels dissecting dermal collagen lined by atypical endothelial cells, is highly characteristic of [...].
Angiosarcoma. Tumour on the scalp.
Angiosarcoma. Primary cutaneous angiosarcoma. The tumour is composed of architecturally complex, anastomosing vessels lined by atypical endothelial cells dissecting between collagen bundles of the dermis.
A: Cutaneous Angiosarcoma
Back Extra: Cutaneous Angiosarcoma
- Clinical: Cutaneous angiosarcoma often presents as erythematous to violaceous plaques or nodules, commonly on sun-damaged skin of the head and neck in elderly patients.
- Micro: Pathologically, angiosarcoma is characterized by complex, anastomosing vessels lined by atypical endothelial cells, which may form solid sheets or exhibit epithelioid morphology.
- Ancillary: Immunohistochemically, angiosarcoma is positive for CD31, CD34, FLI1, and ERG. Radiation- and lymphoedema-associated cases are frequently positive for MYC amplification.
Reference Gallery:
Angiosarcoma. Primary cutaneous angiosarcoma. The tumour is composed of architecturally complex, anastomosing vessels lined by atypical endothelial cells dissecting between collagen bundles of the dermis.
Angiosarcoma. Complex vessels lined by multilayering atypical endothelial cells.
Angiosarcoma. Occasional cases are composed of solid sheets of atypical spindled cells.
Angiosarcoma. Solid sheet-like proliferation with sieve-like vascular lumina.
Angiosarcoma. Neoplastic vessels lined by atypical epithelioid endothelial cells.
Angiosarcoma. Rare cases have tumour cells with abundant foamy cytoplasm resembling histiocytes.
Radiation-induced angiosarcoma. Radiation-induced angiosarcoma with distinctive capillary lobule growth pattern.
Radiation-induced angiosarcoma. The radiation dermatitis pattern of postradiation angiosarcoma consists of thin vascular channels lined by atypical endothelial cells and scattered atypical endothelial cells associated with haemorrhage.
Radiation-induced angiosarcoma. Medium-power image demonstrating proliferation of neoplastic vessels lined by atypical endothelial cells.
Radiation-induced angiosarcoma. An immunohistochemical stain for MYC demonstrates strong nuclear immunoreactivity.
Angiosarcoma. Tumour on the scalp.

Q: Cutaneous Angiosarcoma can arise secondary to radiation therapy or chronic lymphedema; these secondary cases are frequently distinguished from primary cases by amplification and strong nuclear immunoreactivity for [...].
Radiation-induced angiosarcoma. The radiation dermatitis pattern of postradiation angiosarcoma consists of thin vascular channels lined by atypical endothelial cells and scattered atypical endothelial cells associated with haemorrhage.
Radiation-induced angiosarcoma. An immunohistochemical stain for MYC demonstrates strong nuclear immunoreactivity.
A: MYC
Back Extra: Cutaneous Angiosarcoma
- Clinical: Cutaneous angiosarcoma often presents as erythematous to violaceous plaques or nodules, commonly on sun-damaged skin of the head and neck in elderly patients.
- Micro: Pathologically, angiosarcoma is characterized by complex, anastomosing vessels lined by atypical endothelial cells, which may form solid sheets or exhibit epithelioid morphology.
- Ancillary: Immunohistochemically, angiosarcoma is positive for CD31, CD34, FLI1, and ERG. Radiation- and lymphoedema-associated cases are frequently positive for MYC amplification.
Reference Gallery:
Angiosarcoma. Primary cutaneous angiosarcoma. The tumour is composed of architecturally complex, anastomosing vessels lined by atypical endothelial cells dissecting between collagen bundles of the dermis.
Angiosarcoma. Complex vessels lined by multilayering atypical endothelial cells.
Angiosarcoma. Occasional cases are composed of solid sheets of atypical spindled cells.
Angiosarcoma. Solid sheet-like proliferation with sieve-like vascular lumina.
Angiosarcoma. Neoplastic vessels lined by atypical epithelioid endothelial cells.
Angiosarcoma. Rare cases have tumour cells with abundant foamy cytoplasm resembling histiocytes.
Radiation-induced angiosarcoma. Radiation-induced angiosarcoma with distinctive capillary lobule growth pattern.
Radiation-induced angiosarcoma. The radiation dermatitis pattern of postradiation angiosarcoma consists of thin vascular channels lined by atypical endothelial cells and scattered atypical endothelial cells associated with haemorrhage.
Radiation-induced angiosarcoma. Medium-power image demonstrating proliferation of neoplastic vessels lined by atypical endothelial cells.
Radiation-induced angiosarcoma. An immunohistochemical stain for MYC demonstrates strong nuclear immunoreactivity.
Angiosarcoma. Tumour on the scalp.

Q: Histologically, Cutaneous Angiosarcoma often exhibits architecturally complex vessels, but less differentiated areas can form solid sheets of atypical spindled cells containing characteristic [...] vascular lumina.
Angiosarcoma. Occasional cases are composed of solid sheets of atypical spindled cells.
Angiosarcoma. Solid sheet-like proliferation with sieve-like vascular lumina.
A: sieve-like
Back Extra: Cutaneous Angiosarcoma
- Clinical: Cutaneous angiosarcoma often presents as erythematous to violaceous plaques or nodules, commonly on sun-damaged skin of the head and neck in elderly patients.
- Micro: Pathologically, angiosarcoma is characterized by complex, anastomosing vessels lined by atypical endothelial cells, which may form solid sheets or exhibit epithelioid morphology.
- Ancillary: Immunohistochemically, angiosarcoma is positive for CD31, CD34, FLI1, and ERG. Radiation- and lymphoedema-associated cases are frequently positive for MYC amplification.
Reference Gallery:
Angiosarcoma. Primary cutaneous angiosarcoma. The tumour is composed of architecturally complex, anastomosing vessels lined by atypical endothelial cells dissecting between collagen bundles of the dermis.
Angiosarcoma. Complex vessels lined by multilayering atypical endothelial cells.
Angiosarcoma. Occasional cases are composed of solid sheets of atypical spindled cells.
Angiosarcoma. Solid sheet-like proliferation with sieve-like vascular lumina.
Angiosarcoma. Neoplastic vessels lined by atypical epithelioid endothelial cells.
Angiosarcoma. Rare cases have tumour cells with abundant foamy cytoplasm resembling histiocytes.
Radiation-induced angiosarcoma. Radiation-induced angiosarcoma with distinctive capillary lobule growth pattern.
Radiation-induced angiosarcoma. The radiation dermatitis pattern of postradiation angiosarcoma consists of thin vascular channels lined by atypical endothelial cells and scattered atypical endothelial cells associated with haemorrhage.
Radiation-induced angiosarcoma. Medium-power image demonstrating proliferation of neoplastic vessels lined by atypical endothelial cells.
Radiation-induced angiosarcoma. An immunohistochemical stain for MYC demonstrates strong nuclear immunoreactivity.
Angiosarcoma. Tumour on the scalp.

Q: Histologically, an Arteriovenous Malformation consists of a heterogeneous mixture of [...] within a fibromyxomatous background, along with larger-caliber arteries and thick-walled veins.
Arteriovenous malformation. Ill-defined dermal and subcutaneous proliferation of variably sized vascular channels.
Arteriovenous malformation. Small and medium-sized vein- and artery-like congested vascular channels.
A: arterioles, capillaries, and venules
Back Extra: Arteriovenous Malformation
- Clinical: Arteriovenous malformations (AVMs) are characterized by a poorly defined bluish or red mass that may be pulsatile, with variably severe arteriovenous shunting.
- Micro: Histologically, AVMs show a heterogeneous mixture of arterioles, capillaries, and venules within a fibromyxomatous background, along with larger-calibre arteries and thick-walled veins.
- Ancillary: Diagnosis of AVMs typically requires clinicopathological correlation and radiological studies, particularly in small samples.
Reference Gallery:
Arteriovenous malformation. Ill-defined dermal and subcutaneous proliferation of variably sized vascular channels.
Arteriovenous malformation. Small and medium-sized vein- and artery-like congested vascular channels.

Q: The histologic diagnosis of an [...] is characterized by an ill-defined dermal and subcutaneous proliferation of variably sized, congested artery- and vein-like vascular channels.
Arteriovenous malformation. Ill-defined dermal and subcutaneous proliferation of variably sized vascular channels.
Arteriovenous malformation. Small and medium-sized vein- and artery-like congested vascular channels.
A: Arteriovenous Malformation
Back Extra: Arteriovenous Malformation
- Clinical: Arteriovenous malformations (AVMs) are characterized by a poorly defined bluish or red mass that may be pulsatile, with variably severe arteriovenous shunting.
- Micro: Histologically, AVMs show a heterogeneous mixture of arterioles, capillaries, and venules within a fibromyxomatous background, along with larger-calibre arteries and thick-walled veins.
- Ancillary: Diagnosis of AVMs typically requires clinicopathological correlation and radiological studies, particularly in small samples.
Reference Gallery:
Arteriovenous malformation. Ill-defined dermal and subcutaneous proliferation of variably sized vascular channels.
Arteriovenous malformation. Small and medium-sized vein- and artery-like congested vascular channels.

Q: Histologically, Postradiation Atypical Vascular Lesion involves the upper and mid dermis and classically demonstrates a/an [...] architecture composed of irregular, thin-walled, empty lymphatic-like vascular channels.
Atypical vascular lesion. Scanning magnification showing dilated vascular structures in the dermis.
A: inverted V-shaped
Back Extra: Postradiation Atypical Vascular Lesion
- Clinical: Patients typically present with papules, small vesicles, or erythematous ecchymotic plaques with prominent telangiectasia. Most patients are elderly women, and the latency period is usually 2–3 years after radiotherapy.
- Micro: Histologically, the lesion involves the upper and mid dermis, with an inverted V-shaped architecture. It is composed of irregular, branching, anastomosing, thin-walled, empty lymphatic-like vascular channels lined by a single discontinuous layer of endothelial cells with little or no cytological atypia.
- Ancillary: Endothelial cells are positive for ERG, CD34, CD31, podoplanin (D2-40), PROX1, and LYVE1, supporting a lymphatic lineage. The Ki-67 proliferation index is low, and KSHV/HHV8 is negative.
Reference Gallery:
Atypical vascular lesion. Scanning magnification showing dilated vascular structures in the dermis.
Atypical vascular lesion. Higher magnification showing dilated vascular structures lined by atypical endothelial cells.

Q: A proliferation of irregular, thin-walled, dilated vascular channels with little to no cytological atypia that typically presents 2–3 years following radiation therapy is known as [...].
Atypical vascular lesion. Scanning magnification showing dilated vascular structures in the dermis.
Atypical vascular lesion. Higher magnification showing dilated vascular structures lined by atypical endothelial cells.
A: Postradiation Atypical Vascular Lesion
Back Extra: Postradiation Atypical Vascular Lesion
- Clinical: Patients typically present with papules, small vesicles, or erythematous ecchymotic plaques with prominent telangiectasia. Most patients are elderly women, and the latency period is usually 2–3 years after radiotherapy.
- Micro: Histologically, the lesion involves the upper and mid dermis, with an inverted V-shaped architecture. It is composed of irregular, branching, anastomosing, thin-walled, empty lymphatic-like vascular channels lined by a single discontinuous layer of endothelial cells with little or no cytological atypia.
- Ancillary: Endothelial cells are positive for ERG, CD34, CD31, podoplanin (D2-40), PROX1, and LYVE1, supporting a lymphatic lineage. The Ki-67 proliferation index is low, and KSHV/HHV8 is negative.
Reference Gallery:
Atypical vascular lesion. Scanning magnification showing dilated vascular structures in the dermis.
Atypical vascular lesion. Higher magnification showing dilated vascular structures lined by atypical endothelial cells.

Q: [...] is a benign cutaneous vascular tumor histologically characterized by an expansion of the papillary dermis due to a lobular proliferation of dilated, congested capillaries.
Cherry haemangioma. The tumour consists of lobules of dilated capillaries.
A: Cherry Haemangioma
Back Extra: Cherry Haemangioma
- Clinical: Cherry haemangiomas are multiple, tiny, bright red, asymptomatic papules that increase in number with age, commonly affecting the trunk, upper limbs, and less frequently the lower limbs.
- Micro: Histologically, the papillary dermis is expanded by a lobular proliferation of small, dilated, and congested capillaries with a single layer of endothelial cells and an epithelial collarette.
- Ancillary: HRAS and KRAS somatic mutations are found in a small proportion of cases, with frequent mutations in GNA14, GNA11, and GNAQ.
Reference Gallery:
Cherry haemangioma. The tumour consists of lobules of dilated capillaries.
Cherry haemangioma. At high power, dilated and congested capillaries are lined by a single layer of endothelial cells.

Q: Cherry Haemangioma features dilated and congested capillaries that, upon high-power microscopic examination, are characteristically lined by a single layer of [...] without atypia.
Cherry haemangioma. At high power, dilated and congested capillaries are lined by a single layer of endothelial cells.
A: endothelial cells
Back Extra: Cherry Haemangioma
- Clinical: Cherry haemangiomas are multiple, tiny, bright red, asymptomatic papules that increase in number with age, commonly affecting the trunk, upper limbs, and less frequently the lower limbs.
- Micro: Histologically, the papillary dermis is expanded by a lobular proliferation of small, dilated, and congested capillaries with a single layer of endothelial cells and an epithelial collarette.
- Ancillary: HRAS and KRAS somatic mutations are found in a small proportion of cases, with frequent mutations in GNA14, GNA11, and GNAQ.
Reference Gallery:
Cherry haemangioma. The tumour consists of lobules of dilated capillaries.
Cherry haemangioma. At high power, dilated and congested capillaries are lined by a single layer of endothelial cells.

Q: Histologically, Composite Haemangioendothelioma is defined by a complex admixture of distinct vascular patterns, most frequently exhibiting a combination of epithelioid and [...] hemangioendothelioma-like areas.
Composite haemangioendothelioma. Sheets of vacuolated, epithelioid endothelial cells, reminiscent of epithelioid haemangioendothelioma, admixed with vascular channels lined by hobnail endothelial cells.
Composite haemangioendothelioma with neuroendocrine marker expression. Epithelioid endothelial cells adjacent to slit-like vascular channels lined by hobnailed cells.
A: retiform
Back Extra: Composite Haemangioendothelioma
- Clinical: Composite Haemangioendothelioma (CHE) often presents as longstanding reddish-blue nodules or plaques, most commonly on the hands, feet, or head and neck, with a female predominance.
- Micro: Histologically, CHE shows a complex admixture of retiform, spindle cell, epithelioid, and haemangioma-like components, with a distinctive nested appearance and neuroendocrine marker expression in some cases.
- Ancillary: Ancillary studies reveal positive endothelial markers (CD31, CD34, FLI1, ERG) and the presence of YAP1::MAML2 fusions in a subset of cases.
Reference Gallery:
Composite haemangioendothelioma. An example from the arm of a young woman. The most superficial portions of this tumour consisted of infiltrating vascular channels lined by hobnail endothelial cells, reminiscent of retiform haemangioendothelioma.
Composite haemangioendothelioma. Higher-power view of a retiform focus in a composite haemangioendothelioma.
Composite haemangioendothelioma. Sheets of vacuolated, epithelioid endothelial cells, reminiscent of epithelioid haemangioendothelioma, admixed with vascular channels lined by hobnail endothelial cells.
Composite haemangioendothelioma. D2-40 (podoplanin) expression in dermal composite haemangioendothelioma.
Composite haemangioendothelioma with neuroendocrine marker expression. A dermal-based tumour occurring in a middle-aged woman, with superficial vascular channels resembling retiform haemangioendothelioma, as well as deeper collections of nested, epithelioid endothelial cells.
Composite haemangioendothelioma with neuroendocrine marker expression. Retiform and dilated, haemangioma-like vascular channels.
Composite haemangioendothelioma with neuroendocrine marker expression. Epithelioid endothelial cells adjacent to slit-like vascular channels lined by hobnailed cells.
Composite haemangioendothelioma with neuroendocrine marker expression. Synaptophysin expression in neuroendocrine composite haemangioendothelioma.
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like area composed of sheets of epithelioid cells with occasionally prominent cytoplasmic vacuolization.
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like component composed of cords and nests of epithelioid cells in a hyalinized stroma.
Neuroendocrine composite haemangioendothelioma. Retiform haemangioendothelioma–like area from a neuroendocrine composite haemangioendothelioma composed of anastomosing vessels lined by hobnailing endothelium with an appearance reminiscent of rete testis.

Q: A specific histologic subset of Composite Haemangioendothelioma exhibits a distinctive nested architecture of epithelioid cells and is characterized by aberrant expression of [...] immunohistochemical markers (e.g., synaptophysin).
Composite haemangioendothelioma with neuroendocrine marker expression. A dermal-based tumour occurring in a middle-aged woman, with superficial vascular channels resembling retiform haemangioendothelioma, as well as deeper collections of nested, epithelioid endothelial cells.
Composite haemangioendothelioma with neuroendocrine marker expression. Synaptophysin expression in neuroendocrine composite haemangioendothelioma.
A: neuroendocrine
Back Extra: Composite Haemangioendothelioma
- Clinical: Composite Haemangioendothelioma (CHE) often presents as longstanding reddish-blue nodules or plaques, most commonly on the hands, feet, or head and neck, with a female predominance.
- Micro: Histologically, CHE shows a complex admixture of retiform, spindle cell, epithelioid, and haemangioma-like components, with a distinctive nested appearance and neuroendocrine marker expression in some cases.
- Ancillary: Ancillary studies reveal positive endothelial markers (CD31, CD34, FLI1, ERG) and the presence of YAP1::MAML2 fusions in a subset of cases.
Reference Gallery:
Composite haemangioendothelioma. An example from the arm of a young woman. The most superficial portions of this tumour consisted of infiltrating vascular channels lined by hobnail endothelial cells, reminiscent of retiform haemangioendothelioma.
Composite haemangioendothelioma. Higher-power view of a retiform focus in a composite haemangioendothelioma.
Composite haemangioendothelioma. Sheets of vacuolated, epithelioid endothelial cells, reminiscent of epithelioid haemangioendothelioma, admixed with vascular channels lined by hobnail endothelial cells.
Composite haemangioendothelioma. D2-40 (podoplanin) expression in dermal composite haemangioendothelioma.
Composite haemangioendothelioma with neuroendocrine marker expression. A dermal-based tumour occurring in a middle-aged woman, with superficial vascular channels resembling retiform haemangioendothelioma, as well as deeper collections of nested, epithelioid endothelial cells.
Composite haemangioendothelioma with neuroendocrine marker expression. Retiform and dilated, haemangioma-like vascular channels.
Composite haemangioendothelioma with neuroendocrine marker expression. Epithelioid endothelial cells adjacent to slit-like vascular channels lined by hobnailed cells.
Composite haemangioendothelioma with neuroendocrine marker expression. Synaptophysin expression in neuroendocrine composite haemangioendothelioma.
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like area composed of sheets of epithelioid cells with occasionally prominent cytoplasmic vacuolization.
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like component composed of cords and nests of epithelioid cells in a hyalinized stroma.
Neuroendocrine composite haemangioendothelioma. Retiform haemangioendothelioma–like area from a neuroendocrine composite haemangioendothelioma composed of anastomosing vessels lined by hobnailing endothelium with an appearance reminiscent of rete testis.

Q: Microscopically characterized by capillary lobules separated by collagenous septa or variably dilated vascular channels, rapidly involuting (RICH) and non-involuting (NICH) vascular tumors are classified as [...].
Rapidly involuting congenital haemangioma. Lobules of capillaries separated by collagenous septa.
Non-involuting congenital haemangioma. Dermal vascular proliferation composed of variably dilated vascular channels.
Non-involuting congenital haemangioma. Dilated, thin-walled, irregular vascular channels.
A: Congenital Non-Progressive Haemangiomas
Back Extra: Congenital Non-Progressive Haemangiomas
- Clinical: Congenital non-progressive haemangiomas are fully formed at birth and are classified into rapidly involuting (RICH) and non-involuting (NICH) types. RICHs involute spontaneously within the first 6 months, while NICHs persist without regression.
- Micro: Microscopically, RICH, PICH, and NICH show capillary lobules with a fibrotic stroma. NICH and PICH often display arteriovenous shunts and hobnail endothelial cells.
- Ancillary: Somatic activating mutations in GNAQ and GNA11 at Q209 are identified in both RICH and NICH.
Reference Gallery:
Rapidly involuting congenital haemangioma. Lobules of capillaries separated by collagenous septa.
Rapidly involuting congenital haemangioma. Tightly packed capillaries.
Non-involuting congenital haemangioma. Dermal vascular proliferation composed of variably dilated vascular channels.
Non-involuting congenital haemangioma. Dilated, thin-walled, irregular vascular channels.

Q: In Congenital Non-Progressive Haemangiomas, the [...] variant (RICH) is characterized histologically by tightly packed capillary lobules separated by prominent collagenous septa.
Rapidly involuting congenital haemangioma. Lobules of capillaries separated by collagenous septa.
Rapidly involuting congenital haemangioma. Tightly packed capillaries.
A: rapidly involuting
Back Extra: Congenital Non-Progressive Haemangiomas
- Clinical: Congenital non-progressive haemangiomas are fully formed at birth and are classified into rapidly involuting (RICH) and non-involuting (NICH) types. RICHs involute spontaneously within the first 6 months, while NICHs persist without regression.
- Micro: Microscopically, RICH, PICH, and NICH show capillary lobules with a fibrotic stroma. NICH and PICH often display arteriovenous shunts and hobnail endothelial cells.
- Ancillary: Somatic activating mutations in GNAQ and GNA11 at Q209 are identified in both RICH and NICH.
Reference Gallery:
Rapidly involuting congenital haemangioma. Lobules of capillaries separated by collagenous septa.
Rapidly involuting congenital haemangioma. Tightly packed capillaries.
Non-involuting congenital haemangioma. Dermal vascular proliferation composed of variably dilated vascular channels.
Non-involuting congenital haemangioma. Dilated, thin-walled, irregular vascular channels.

Q: In Congenital Non-Progressive Haemangiomas, the [...] variant (NICH) persistently shows a dermal vascular proliferation composed of variably dilated, thin-walled, irregular vascular channels.
Non-involuting congenital haemangioma. Dermal vascular proliferation composed of variably dilated vascular channels.
Non-involuting congenital haemangioma. Dilated, thin-walled, irregular vascular channels.
A: non-involuting
Back Extra: Congenital Non-Progressive Haemangiomas
- Clinical: Congenital non-progressive haemangiomas are fully formed at birth and are classified into rapidly involuting (RICH) and non-involuting (NICH) types. RICHs involute spontaneously within the first 6 months, while NICHs persist without regression.
- Micro: Microscopically, RICH, PICH, and NICH show capillary lobules with a fibrotic stroma. NICH and PICH often display arteriovenous shunts and hobnail endothelial cells.
- Ancillary: Somatic activating mutations in GNAQ and GNA11 at Q209 are identified in both RICH and NICH.
Reference Gallery:
Rapidly involuting congenital haemangioma. Lobules of capillaries separated by collagenous septa.
Rapidly involuting congenital haemangioma. Tightly packed capillaries.
Non-involuting congenital haemangioma. Dermal vascular proliferation composed of variably dilated vascular channels.
Non-involuting congenital haemangioma. Dilated, thin-walled, irregular vascular channels.

Q: A well-circumscribed, dermal vascular tumor composed of sheets of epithelioid endothelial cells with intracytoplasmic vacuoles and surrounding SMA-positive pericytes is characteristic of a [...].
Cutaneous epithelioid angiomatous nodule. Epithelioid endothelial cells are arranged in sheets. They have abundant eosinophilic cytoplasm and contain vesicular nuclei with small eosinophilic nucleoli; intracytoplasmic lumina are focally present. A mitotic figure is visible in the upper-right corner; also note the presence of well-formed intralesional vascular channels.
Cutaneous epithelioid angiomatous nodule. SMA immunohistochemistry demonstrates pericytes surrounding the endothelial cells.
A: Cutaneous Epithelioid Angiomatous Nodule
Back Extra: Cutaneous Epithelioid Angiomatous Nodule
- Clinical: Cutaneous epithelioid angiomatous nodules appear as solitary papules and nodules with erythematous to bluish discolouration, typically < 15 mm in size, with a peak incidence in young to middle-aged adults.
- Micro: The tumours are well-circumscribed nodules in the dermis, composed of solid sheets of large polygonal epithelioid cells with abundant cytoplasm, vesicular nuclei, and small eosinophilic nucleoli. Intracytoplasmic vacuoles and intralesional vascular channels are focal features.
- Ancillary: Immunohistochemically, the tumour cells express endothelial cell markers (CD31, CD34, and factor VIII), and SMA-positive pericytes are present. Immunohistochemistry for FOSB is negative.
Reference Gallery:
Cutaneous epithelioid angiomatous nodule. The tumour is nodular and well circumscribed; it is based within the dermis, with surrounding haemosiderin deposition.
Cutaneous epithelioid angiomatous nodule. Epithelioid endothelial cells are arranged in sheets. They have abundant eosinophilic cytoplasm and contain vesicular nuclei with small eosinophilic nucleoli; intracytoplasmic lumina are focally present. A mitotic figure is visible in the upper-right corner; also note the presence of well-formed intralesional vascular channels.
Cutaneous epithelioid angiomatous nodule. CD31 immunohistochemistry highlights endothelial cells.
Cutaneous epithelioid angiomatous nodule. SMA immunohistochemistry demonstrates pericytes surrounding the endothelial cells.

Q: Microscopically, the epithelioid endothelial cells of a Cutaneous Epithelioid Angiomatous Nodule are arranged in solid sheets and focally display characteristic [...] (or lumina).
Cutaneous epithelioid angiomatous nodule. Epithelioid endothelial cells are arranged in sheets. They have abundant eosinophilic cytoplasm and contain vesicular nuclei with small eosinophilic nucleoli; intracytoplasmic lumina are focally present. A mitotic figure is visible in the upper-right corner; also note the presence of well-formed intralesional vascular channels.
A: intracytoplasmic vacuoles
Back Extra: Cutaneous Epithelioid Angiomatous Nodule
- Clinical: Cutaneous epithelioid angiomatous nodules appear as solitary papules and nodules with erythematous to bluish discolouration, typically < 15 mm in size, with a peak incidence in young to middle-aged adults.
- Micro: The tumours are well-circumscribed nodules in the dermis, composed of solid sheets of large polygonal epithelioid cells with abundant cytoplasm, vesicular nuclei, and small eosinophilic nucleoli. Intracytoplasmic vacuoles and intralesional vascular channels are focal features.
- Ancillary: Immunohistochemically, the tumour cells express endothelial cell markers (CD31, CD34, and factor VIII), and SMA-positive pericytes are present. Immunohistochemistry for FOSB is negative.
Reference Gallery:
Cutaneous epithelioid angiomatous nodule. The tumour is nodular and well circumscribed; it is based within the dermis, with surrounding haemosiderin deposition.
Cutaneous epithelioid angiomatous nodule. Epithelioid endothelial cells are arranged in sheets. They have abundant eosinophilic cytoplasm and contain vesicular nuclei with small eosinophilic nucleoli; intracytoplasmic lumina are focally present. A mitotic figure is visible in the upper-right corner; also note the presence of well-formed intralesional vascular channels.
Cutaneous epithelioid angiomatous nodule. CD31 immunohistochemistry highlights endothelial cells.
Cutaneous epithelioid angiomatous nodule. SMA immunohistochemistry demonstrates pericytes surrounding the endothelial cells.

Q: In a Cutaneous Epithelioid Angiomatous Nodule, immunohistochemistry reveals CD31-positive endothelial cells that are distinctly surrounded by a layer of SMA-positive [...].
Cutaneous epithelioid angiomatous nodule. CD31 immunohistochemistry highlights endothelial cells.
Cutaneous epithelioid angiomatous nodule. SMA immunohistochemistry demonstrates pericytes surrounding the endothelial cells.
A: pericytes
Back Extra: Cutaneous Epithelioid Angiomatous Nodule
- Clinical: Cutaneous epithelioid angiomatous nodules appear as solitary papules and nodules with erythematous to bluish discolouration, typically < 15 mm in size, with a peak incidence in young to middle-aged adults.
- Micro: The tumours are well-circumscribed nodules in the dermis, composed of solid sheets of large polygonal epithelioid cells with abundant cytoplasm, vesicular nuclei, and small eosinophilic nucleoli. Intracytoplasmic vacuoles and intralesional vascular channels are focal features.
- Ancillary: Immunohistochemically, the tumour cells express endothelial cell markers (CD31, CD34, and factor VIII), and SMA-positive pericytes are present. Immunohistochemistry for FOSB is negative.
Reference Gallery:
Cutaneous epithelioid angiomatous nodule. The tumour is nodular and well circumscribed; it is based within the dermis, with surrounding haemosiderin deposition.
Cutaneous epithelioid angiomatous nodule. Epithelioid endothelial cells are arranged in sheets. They have abundant eosinophilic cytoplasm and contain vesicular nuclei with small eosinophilic nucleoli; intracytoplasmic lumina are focally present. A mitotic figure is visible in the upper-right corner; also note the presence of well-formed intralesional vascular channels.
Cutaneous epithelioid angiomatous nodule. CD31 immunohistochemistry highlights endothelial cells.
Cutaneous epithelioid angiomatous nodule. SMA immunohistochemistry demonstrates pericytes surrounding the endothelial cells.

Q: Histologically, Epithelioid Haemangioendothelioma is composed of bland epithelioid cells arranged in cords and nests within a myxohyaline stroma, characteristically featuring [...].
Epithelioid haemangioendothelioma. The tumour is composed of cords of epithelioid cells with pale cytoplasm, infiltrating the dermis.
Epithelioid haemangioendothelioma. Glassy eosinophilic cytoplasm is a characteristic feature. Note the intracytoplasmic vacuoles.
A: intracytoplasmic vacuoles
Back Extra: Epithelioid Haemangioendothelioma
- Clinical: Epithelioid Haemangioendothelioma (EHE) most often arises in middle-aged adults, with a slight female predominance. Clinical features include nondescript nodules, sometimes with a thickened epidermis or ulceration.
- Micro: EHE is composed of relatively bland epithelioid cells with intracytoplasmic vacuoles, arranged in cords and nests within a myxohyaline stroma. The YAP1::TFE3 subtype shows a nested and vasoformative architecture.
- Ancillary: Immunohistochemically, EHE is positive for CD31, FLI1, and ERG. The WWTR1::CAMTA1 fusion is confirmed by strong nuclear CAMTA1 expression, while the YAP1::TFE3 fusion is confirmed by diffuse nuclear TFE3 expression and loss of YAP1 C-terminus expression.
Reference Gallery:
Epithelioid haemangioendothelioma. Cutaneous epithelioid haemangioendothelioma with overlying epidermal hyperplasia.
Epithelioid haemangioendothelioma. The tumour is composed of cords of epithelioid cells with pale cytoplasm, infiltrating the dermis.
Epithelioid haemangioendothelioma. Glassy eosinophilic cytoplasm is a characteristic feature. Note the intracytoplasmic vacuoles.
Epithelioid haemangioendothelioma. CD31 expression confirms endothelial differentiation.
Epithelioid haemangioendothelioma. Nuclear CAMTA1 reflects the underlying WWTR1::CAMTA1 fusion of conventional epithelioid haemangioendothelioma.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Cutaneous examples of this subtype are extremely rare. The vascular nature of the tumour can be appreciated.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. A nested architecture is characteristic. Note the abundant eosinophilic cytoplasm.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Most examples show focal vasoformative architecture.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Strong nuclear TFE3 expression is typical of this subtype.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Loss of expression of the C-terminus of YAP1 is highly specific for YAP1::TFE3 fusion.

Q: Conventional Epithelioid Haemangioendothelioma harbors a WWTR1::CAMTA1 fusion, which is confirmed immunohistochemically by strong nuclear expression of [...].
Epithelioid haemangioendothelioma. Nuclear CAMTA1 reflects the underlying WWTR1::CAMTA1 fusion of conventional epithelioid haemangioendothelioma.
A: CAMTA1
Back Extra: Epithelioid Haemangioendothelioma
- Clinical: Epithelioid Haemangioendothelioma (EHE) most often arises in middle-aged adults, with a slight female predominance. Clinical features include nondescript nodules, sometimes with a thickened epidermis or ulceration.
- Micro: EHE is composed of relatively bland epithelioid cells with intracytoplasmic vacuoles, arranged in cords and nests within a myxohyaline stroma. The YAP1::TFE3 subtype shows a nested and vasoformative architecture.
- Ancillary: Immunohistochemically, EHE is positive for CD31, FLI1, and ERG. The WWTR1::CAMTA1 fusion is confirmed by strong nuclear CAMTA1 expression, while the YAP1::TFE3 fusion is confirmed by diffuse nuclear TFE3 expression and loss of YAP1 C-terminus expression.
Reference Gallery:
Epithelioid haemangioendothelioma. Cutaneous epithelioid haemangioendothelioma with overlying epidermal hyperplasia.
Epithelioid haemangioendothelioma. The tumour is composed of cords of epithelioid cells with pale cytoplasm, infiltrating the dermis.
Epithelioid haemangioendothelioma. Glassy eosinophilic cytoplasm is a characteristic feature. Note the intracytoplasmic vacuoles.
Epithelioid haemangioendothelioma. CD31 expression confirms endothelial differentiation.
Epithelioid haemangioendothelioma. Nuclear CAMTA1 reflects the underlying WWTR1::CAMTA1 fusion of conventional epithelioid haemangioendothelioma.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Cutaneous examples of this subtype are extremely rare. The vascular nature of the tumour can be appreciated.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. A nested architecture is characteristic. Note the abundant eosinophilic cytoplasm.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Most examples show focal vasoformative architecture.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Strong nuclear TFE3 expression is typical of this subtype.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Loss of expression of the C-terminus of YAP1 is highly specific for YAP1::TFE3 fusion.

Q: The YAP1::TFE3 subtype of Epithelioid Haemangioendothelioma frequently displays a vasoformative and nested architecture, and is uniquely confirmed by strong nuclear TFE3 positivity coupled with loss of [...] expression.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. A nested architecture is characteristic. Note the abundant eosinophilic cytoplasm.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Strong nuclear TFE3 expression is typical of this subtype.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Loss of expression of the C-terminus of YAP1 is highly specific for YAP1::TFE3 fusion.
A: YAP1 C-terminus
Back Extra: Epithelioid Haemangioendothelioma
- Clinical: Epithelioid Haemangioendothelioma (EHE) most often arises in middle-aged adults, with a slight female predominance. Clinical features include nondescript nodules, sometimes with a thickened epidermis or ulceration.
- Micro: EHE is composed of relatively bland epithelioid cells with intracytoplasmic vacuoles, arranged in cords and nests within a myxohyaline stroma. The YAP1::TFE3 subtype shows a nested and vasoformative architecture.
- Ancillary: Immunohistochemically, EHE is positive for CD31, FLI1, and ERG. The WWTR1::CAMTA1 fusion is confirmed by strong nuclear CAMTA1 expression, while the YAP1::TFE3 fusion is confirmed by diffuse nuclear TFE3 expression and loss of YAP1 C-terminus expression.
Reference Gallery:
Epithelioid haemangioendothelioma. Cutaneous epithelioid haemangioendothelioma with overlying epidermal hyperplasia.
Epithelioid haemangioendothelioma. The tumour is composed of cords of epithelioid cells with pale cytoplasm, infiltrating the dermis.
Epithelioid haemangioendothelioma. Glassy eosinophilic cytoplasm is a characteristic feature. Note the intracytoplasmic vacuoles.
Epithelioid haemangioendothelioma. CD31 expression confirms endothelial differentiation.
Epithelioid haemangioendothelioma. Nuclear CAMTA1 reflects the underlying WWTR1::CAMTA1 fusion of conventional epithelioid haemangioendothelioma.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Cutaneous examples of this subtype are extremely rare. The vascular nature of the tumour can be appreciated.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. A nested architecture is characteristic. Note the abundant eosinophilic cytoplasm.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Most examples show focal vasoformative architecture.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Strong nuclear TFE3 expression is typical of this subtype.
Epithelioid haemangioendothelioma subtype with YAP1::TFE3. Loss of expression of the C-terminus of YAP1 is highly specific for YAP1::TFE3 fusion.

Q: A skin-colored to erythematous nodule characterized histologically by a dermal lobular vascular proliferation with a prominent mixed inflammatory infiltrate (often rich in eosinophils) is diagnostic of [...].
Epithelioid haemangioma. Dermal lobular vascular proliferation obscured by prominent inflammation.
Epithelioid haemangioma. Vascular channels with prominent epithelioid cells associated with fibrosis and inflammatory cells, mainly lymphocytes and eosinophils.
A: Epithelioid Haemangioma
Back Extra: Epithelioid Haemangioma
- Clinical: Epithelioid haemangioma (EH) manifests as single or multiple, persistent, skin-coloured to erythematous papules and nodules, often with peripheral eosinophilia in 15% of patients.
- Micro: EH is characterized by a lobular proliferation of vascular channels lined by bland epithelioid endothelial cells with an associated inflammatory infiltrate of lymphocytes, histiocytes, plasma cells, and eosinophils.
- Ancillary: Immunohistochemistry shows positive staining for blood vascular markers, SMA-positive pericyte layer, and frequent FOSB nuclear staining, but lacks lymphatic markers.
Reference Gallery:
Epithelioid haemangioma. Dermal lobular vascular proliferation obscured by prominent inflammation.
Epithelioid haemangioma. Vascular channels with prominent epithelioid cells associated with fibrosis and inflammatory cells, mainly lymphocytes and eosinophils.
Epithelioid haemangioma. Vascular channels lined by prominent epithelioid endothelial cells.

Q: In Epithelioid Haemangioma, the vascular channels are characteristically lined by plump, bland cells known as [...].
Epithelioid haemangioma. Vascular channels lined by prominent epithelioid endothelial cells.
A: epithelioid endothelial cells
Back Extra: Epithelioid Haemangioma
- Clinical: Epithelioid haemangioma (EH) manifests as single or multiple, persistent, skin-coloured to erythematous papules and nodules, often with peripheral eosinophilia in 15% of patients.
- Micro: EH is characterized by a lobular proliferation of vascular channels lined by bland epithelioid endothelial cells with an associated inflammatory infiltrate of lymphocytes, histiocytes, plasma cells, and eosinophils.
- Ancillary: Immunohistochemistry shows positive staining for blood vascular markers, SMA-positive pericyte layer, and frequent FOSB nuclear staining, but lacks lymphatic markers.
Reference Gallery:
Epithelioid haemangioma. Dermal lobular vascular proliferation obscured by prominent inflammation.
Epithelioid haemangioma. Vascular channels with prominent epithelioid cells associated with fibrosis and inflammatory cells, mainly lymphocytes and eosinophils.
Epithelioid haemangioma. Vascular channels lined by prominent epithelioid endothelial cells.

Q: Microscopic examination of a Glomeruloid Haemangioma typically reveals a dermal proliferation of dilated vascular channels containing capillary clusters that closely resemble [...].
Glomeruloid haemangioma. High-power image demonstrates intravascular capillary proliferation resembling a renal glomerulus.
A: renal glomeruli
Back Extra: Glomeruloid Haemangioma
- Clinical: Multiple erythematous papules affecting the trunk and extremities, often seen in the context of multicentric Castleman disease or POEMS syndrome.
- Micro: Dermal proliferation of dilated vascular channels containing clusters of capillaries that resemble renal glomeruli, with endothelial cells containing PAS-positive intracytoplasmic inclusions.
- Ancillary: Not relevant for diagnosis.
Reference Gallery:
Glomeruloid haemangioma. High-power image demonstrates intravascular capillary proliferation resembling a renal glomerulus.

Q: A typical Glomus Tumor is characterized by nests of round cells arranged around small vessels, featuring a central round nucleus, eosinophilic cytoplasm, and a [...].
Glomus tumour (typical). The circumscribed edge of this glomus tumour is intimately associated with a rim of small-calibre nerves. The bulk of the lesion is formed by sheets of round glomus cells arranged around scattered small vessels.
Glomus tumour (typical). The typical appearance of glomus cells is seen here, with the cells having a central round nucleus, eosinophilic cytoplasm, and a well-defined cytoplasmic membrane.
A: sharp cellular outline
Back Extra: Glomus Tumor
- Clinical: Glomus tumors are typically solitary, small (<10 mm), painful nodules or plaques with a pink to blue hue, often found in the digits and subungual regions.
- Micro: Glomus tumors are composed of nests of round glomus cells with a central round nucleus, eosinophilic cytoplasm, and a sharp cellular outline.
- Ancillary: Glomus tumors typically express smooth muscle actin (SMA), h-caldesmon, and pericellular collagen IV.
Reference Gallery:
Glomuvenous malformation. The defining feature of glomuvenous malformation is the presence of increased numbers of benign-appearing glomus cells within the walls of the vascular malformation.
Glomuvenous malformation. Higher-power view of glomus cells within vascular smooth muscle.
Symplastic glomus tumour. Degenerative-appearing nuclear atypia without mitotic activity characterizes symplastic glomus tumour.
Malignant glomus tumour. High nuclear grade and easily identified mitotic activity in malignant glomus tumour.
Malignant glomus tumour. Spindle cell morphology is relatively common in malignant glomus tumour. The cells tend to be somewhat smaller and less distinctly eosinophilic than those of leiomyosarcoma.
Glomus tumour of uncertain malignant potential. This tumour showed clear demarcation between a typical, benign-appearing component (right) and an atypical component (left). The latter showed moderate nuclear pleomorphism and scattered multinucleated cells, but without mitotic activity.
Glomus tumour (typical). The circumscribed edge of this glomus tumour is intimately associated with a rim of small-calibre nerves. The bulk of the lesion is formed by sheets of round glomus cells arranged around scattered small vessels.
Glomus tumour (typical). The typical appearance of glomus cells is seen here, with the cells having a central round nucleus, eosinophilic cytoplasm, and a well-defined cytoplasmic membrane.
Glomus tumour of uncertain malignant potential. Coexisting typical and atypical components are present, the latter with moderate nuclear grade but insufficient mitotic activity for a diagnosis of malignant.
Typical glomus tumour. Glomus cells show uniform strong immunostaining for SMA.

Q: By immunohistochemistry, the characteristic round cells in a Glomus Tumor typically show uniform, strong staining for [...].
Typical glomus tumour. Glomus cells show uniform strong immunostaining for SMA.
A: smooth muscle actin (SMA)
Back Extra: Glomus Tumor
- Clinical: Glomus tumors are typically solitary, small (<10 mm), painful nodules or plaques with a pink to blue hue, often found in the digits and subungual regions.
- Micro: Glomus tumors are composed of nests of round glomus cells with a central round nucleus, eosinophilic cytoplasm, and a sharp cellular outline.
- Ancillary: Glomus tumors typically express smooth muscle actin (SMA), h-caldesmon, and pericellular collagen IV.
Reference Gallery:
Glomuvenous malformation. The defining feature of glomuvenous malformation is the presence of increased numbers of benign-appearing glomus cells within the walls of the vascular malformation.
Glomuvenous malformation. Higher-power view of glomus cells within vascular smooth muscle.
Symplastic glomus tumour. Degenerative-appearing nuclear atypia without mitotic activity characterizes symplastic glomus tumour.
Malignant glomus tumour. High nuclear grade and easily identified mitotic activity in malignant glomus tumour.
Malignant glomus tumour. Spindle cell morphology is relatively common in malignant glomus tumour. The cells tend to be somewhat smaller and less distinctly eosinophilic than those of leiomyosarcoma.
Glomus tumour of uncertain malignant potential. This tumour showed clear demarcation between a typical, benign-appearing component (right) and an atypical component (left). The latter showed moderate nuclear pleomorphism and scattered multinucleated cells, but without mitotic activity.
Glomus tumour (typical). The circumscribed edge of this glomus tumour is intimately associated with a rim of small-calibre nerves. The bulk of the lesion is formed by sheets of round glomus cells arranged around scattered small vessels.
Glomus tumour (typical). The typical appearance of glomus cells is seen here, with the cells having a central round nucleus, eosinophilic cytoplasm, and a well-defined cytoplasmic membrane.
Glomus tumour of uncertain malignant potential. Coexisting typical and atypical components are present, the latter with moderate nuclear grade but insufficient mitotic activity for a diagnosis of malignant.
Typical glomus tumour. Glomus cells show uniform strong immunostaining for SMA.

Q: A symplastic Glomus Tumor is defined by the presence of marked, degenerative-appearing nuclear atypia but explicitly lacks [...].
Symplastic glomus tumour. Degenerative-appearing nuclear atypia without mitotic activity characterizes symplastic glomus tumour.
A: mitotic activity
Back Extra: Glomus Tumor
- Clinical: Glomus tumors are typically solitary, small (<10 mm), painful nodules or plaques with a pink to blue hue, often found in the digits and subungual regions.
- Micro: Glomus tumors are composed of nests of round glomus cells with a central round nucleus, eosinophilic cytoplasm, and a sharp cellular outline.
- Ancillary: Glomus tumors typically express smooth muscle actin (SMA), h-caldesmon, and pericellular collagen IV.
Reference Gallery:
Glomuvenous malformation. The defining feature of glomuvenous malformation is the presence of increased numbers of benign-appearing glomus cells within the walls of the vascular malformation.
Glomuvenous malformation. Higher-power view of glomus cells within vascular smooth muscle.
Symplastic glomus tumour. Degenerative-appearing nuclear atypia without mitotic activity characterizes symplastic glomus tumour.
Malignant glomus tumour. High nuclear grade and easily identified mitotic activity in malignant glomus tumour.
Malignant glomus tumour. Spindle cell morphology is relatively common in malignant glomus tumour. The cells tend to be somewhat smaller and less distinctly eosinophilic than those of leiomyosarcoma.
Glomus tumour of uncertain malignant potential. This tumour showed clear demarcation between a typical, benign-appearing component (right) and an atypical component (left). The latter showed moderate nuclear pleomorphism and scattered multinucleated cells, but without mitotic activity.
Glomus tumour (typical). The circumscribed edge of this glomus tumour is intimately associated with a rim of small-calibre nerves. The bulk of the lesion is formed by sheets of round glomus cells arranged around scattered small vessels.
Glomus tumour (typical). The typical appearance of glomus cells is seen here, with the cells having a central round nucleus, eosinophilic cytoplasm, and a well-defined cytoplasmic membrane.
Glomus tumour of uncertain malignant potential. Coexisting typical and atypical components are present, the latter with moderate nuclear grade but insufficient mitotic activity for a diagnosis of malignant.
Typical glomus tumour. Glomus cells show uniform strong immunostaining for SMA.

Q: Architecturally, the irregular, thin-walled vascular channels in Hobnail hemangioma are classically described as [...], showing dilated superficial channels that progressively decrease in size in the deeper dermis.
Hobnail haemangioma. Dilated, irregular, thin-walled vascular channels in the superficial dermis, with progressive decrease in the deeper dermis.
A: wedge-shaped
Back Extra: Hobnail Haemangioma
- Clinical: Hobnail haemangioma occurs mainly in young and middle-aged adults, often presenting as small, nondescript erythematous papules, typically on the trunk and extremities.
- Micro: This lesion is characterized by wedge-shaped, thin-walled, irregular vascular channels lined by bland endothelial cells with a hobnail appearance.
- Ancillary: Endothelial cells are strongly positive for podoplanin (D2-40) and usually negative or weakly positive for CD34.
Reference Gallery:
Hobnail haemangioma. Dilated, irregular, thin-walled vascular channels in the superficial dermis, with progressive decrease in the deeper dermis.
Hobnail haemangioma. Dilated, lymphatic-like channels with focal papillary projections. Haemosiderin is seen in the background.
Hobnail haemangioma. Vascular channels lined by bland hobnail endothelial cells.

Q: In Hobnail hemangioma, the dilated, lymphatic-like vascular channels are typically lined by bland endothelial cells that exhibit a characteristic [...] appearance, often accompanied by background hemosiderin and focal papillary projections.
Hobnail haemangioma. Dilated, lymphatic-like channels with focal papillary projections. Haemosiderin is seen in the background.
Hobnail haemangioma. Vascular channels lined by bland hobnail endothelial cells.
A: hobnail
Back Extra: Hobnail Haemangioma
- Clinical: Hobnail haemangioma occurs mainly in young and middle-aged adults, often presenting as small, nondescript erythematous papules, typically on the trunk and extremities.
- Micro: This lesion is characterized by wedge-shaped, thin-walled, irregular vascular channels lined by bland endothelial cells with a hobnail appearance.
- Ancillary: Endothelial cells are strongly positive for podoplanin (D2-40) and usually negative or weakly positive for CD34.
Reference Gallery:
Hobnail haemangioma. Dilated, irregular, thin-walled vascular channels in the superficial dermis, with progressive decrease in the deeper dermis.
Hobnail haemangioma. Dilated, lymphatic-like channels with focal papillary projections. Haemosiderin is seen in the background.
Hobnail haemangioma. Vascular channels lined by bland hobnail endothelial cells.

Q: In the early proliferative stage of Infantile Haemangioma, the tumor is histologically characterized by cellular dermal [...] of tightly packed capillaries lined by plump endothelial cells.
Infantile haemangioma. Early stage consisting of lobules of capillaries.
A: lobules
Back Extra: Infantile Haemangioma
- Clinical: Infantile haemangiomas typically appear in the first 2–6 weeks of life, as bright-red or blue nodules or plaques, often with a strawberry-like appearance.
- Micro: The early proliferative stage of infantile haemangioma consists of cellular dermal masses of tightly packed capillaries with small lumina, lined by plump endothelial cells.
- Ancillary: GLUT1 positivity is a key diagnostic marker for infantile haemangioma, distinguishing it from congenital non-progressive haemangiomas.
Reference Gallery:
Infantile haemangioma. Early stage consisting of lobules of capillaries.
Infantile haemangioma. Involuting stage. Early fibrosis within tumour lobules.
Infantile haemangioma. Late stage. Prominent perivascular fibrosis.

Q: As an Infantile Haemangioma enters the involuting and late stages, the capillary structures are progressively replaced by prominent perivascular and intralesional [...].
Infantile haemangioma. Involuting stage. Early fibrosis within tumour lobules.
Infantile haemangioma. Late stage. Prominent perivascular fibrosis.
A: fibrosis
Back Extra: Infantile Haemangioma
- Clinical: Infantile haemangiomas typically appear in the first 2–6 weeks of life, as bright-red or blue nodules or plaques, often with a strawberry-like appearance.
- Micro: The early proliferative stage of infantile haemangioma consists of cellular dermal masses of tightly packed capillaries with small lumina, lined by plump endothelial cells.
- Ancillary: GLUT1 positivity is a key diagnostic marker for infantile haemangioma, distinguishing it from congenital non-progressive haemangiomas.
Reference Gallery:
Infantile haemangioma. Early stage consisting of lobules of capillaries.
Infantile haemangioma. Involuting stage. Early fibrosis within tumour lobules.
Infantile haemangioma. Late stage. Prominent perivascular fibrosis.

Q: Early patch-stage Kaposi Sarcoma exhibits subtle endothelial cell proliferation dissecting through dermal collagen, frequently demonstrating the characteristic [...].
Kaposi sarcoma. Patch-stage Kaposi sarcoma; there is dissection of dermal collagen by a subtle vasoformative proliferation, and the promontory sign is evident.
A: promontory sign
Back Extra: Kaposi Sarcoma
- Clinical: Kaposi sarcoma (KS) presents as purplish cutaneous lesions that can range from small patches to large nodules, often with associated lymphoedema in the lower limbs.
- Micro: Patch-stage KS shows subtle endothelial cell proliferation with dermal collagen dissection and the promontory sign, while nodular KS exhibits fascicles of mitotically active spindled cells and slit-like spaces containing red blood cells.
- Ancillary: Kaposi sarcoma is diagnosed by detecting KSHV/HHV8 in lesional tissue using PCR, in situ hybridization, and immunohistochemical staining for LANA1, CD34, CD31, and podoplanin.
Reference Gallery:
Kaposi sarcoma. Plaque-stage Kaposi sarcoma; hyperpigmented plaques are present on the hands.
Kaposi sarcoma. Nodular Kaposi sarcoma; a large vulval tumour with ulceration.
Kaposi sarcoma. Nodular and verrucous Kaposi sarcoma; numerous nodular and hyperkeratotic lesions are present in a background of associated lymphoedema.
Kaposi sarcoma. Patch-stage Kaposi sarcoma; there is dissection of dermal collagen by a subtle vasoformative proliferation, and the promontory sign is evident.
Kaposi sarcoma. Plaque-stage Kaposi sarcoma; a more cellular proliferation, extensive erythrocytic extravasation, haemosiderin pigment deposition, and a focal mononuclear inflammatory cell infiltrate are seen.
Kaposi sarcoma. Nodular Kaposi sarcoma; there are fascicles of mitotically active spindled cells, slit-like spaces containing red blood cells, and scattered hyaline globules.
Kaposi sarcoma. Nodular Kaposi sarcoma; strongly positive immunohistochemical staining for podoplanin (recognized by the D2-40 antibody).
Kaposi sarcoma. Nodular Kaposi sarcoma; positive nuclear staining with an antibody to KSHV/HHV8 LANA1.
Kaposi sarcoma. Lymphangioma-like Kaposi sarcoma; the dermis is expanded by interanastomosing lymphangiomatous-looking channels.
Kaposi sarcoma. Anaplastic (pleomorphic) Kaposi sarcoma; there is cellular atypia, focal necrosis, and an absence of obvious vasoformative features.
Kaposi sarcoma. FNAC specimen from a nodule on the leg of a man with HIV infection; there is a loosely cohesive cluster of bland spindled cells, with altered blood present in the background.
Kaposi sarcoma (KS). Age-standardized incidence rates (ASIRs) in 2020 of HIV-attributable (epidemic) KS (A) and non–HIV-attributable (classic/endemic/iatrogenic) KS (B).

Q: The advanced nodular stage of Kaposi Sarcoma is characterized by fascicles of mitotically active spindled cells forming [...] that contain extravasated red blood cells and scattered hyaline globules.
Kaposi sarcoma. Nodular Kaposi sarcoma; there are fascicles of mitotically active spindled cells, slit-like spaces containing red blood cells, and scattered hyaline globules.
A: slit-like spaces
Back Extra: Kaposi Sarcoma
- Clinical: Kaposi sarcoma (KS) presents as purplish cutaneous lesions that can range from small patches to large nodules, often with associated lymphoedema in the lower limbs.
- Micro: Patch-stage KS shows subtle endothelial cell proliferation with dermal collagen dissection and the promontory sign, while nodular KS exhibits fascicles of mitotically active spindled cells and slit-like spaces containing red blood cells.
- Ancillary: Kaposi sarcoma is diagnosed by detecting KSHV/HHV8 in lesional tissue using PCR, in situ hybridization, and immunohistochemical staining for LANA1, CD34, CD31, and podoplanin.
Reference Gallery:
Kaposi sarcoma. Plaque-stage Kaposi sarcoma; hyperpigmented plaques are present on the hands.
Kaposi sarcoma. Nodular Kaposi sarcoma; a large vulval tumour with ulceration.
Kaposi sarcoma. Nodular and verrucous Kaposi sarcoma; numerous nodular and hyperkeratotic lesions are present in a background of associated lymphoedema.
Kaposi sarcoma. Patch-stage Kaposi sarcoma; there is dissection of dermal collagen by a subtle vasoformative proliferation, and the promontory sign is evident.
Kaposi sarcoma. Plaque-stage Kaposi sarcoma; a more cellular proliferation, extensive erythrocytic extravasation, haemosiderin pigment deposition, and a focal mononuclear inflammatory cell infiltrate are seen.
Kaposi sarcoma. Nodular Kaposi sarcoma; there are fascicles of mitotically active spindled cells, slit-like spaces containing red blood cells, and scattered hyaline globules.
Kaposi sarcoma. Nodular Kaposi sarcoma; strongly positive immunohistochemical staining for podoplanin (recognized by the D2-40 antibody).
Kaposi sarcoma. Nodular Kaposi sarcoma; positive nuclear staining with an antibody to KSHV/HHV8 LANA1.
Kaposi sarcoma. Lymphangioma-like Kaposi sarcoma; the dermis is expanded by interanastomosing lymphangiomatous-looking channels.
Kaposi sarcoma. Anaplastic (pleomorphic) Kaposi sarcoma; there is cellular atypia, focal necrosis, and an absence of obvious vasoformative features.
Kaposi sarcoma. FNAC specimen from a nodule on the leg of a man with HIV infection; there is a loosely cohesive cluster of bland spindled cells, with altered blood present in the background.
Kaposi sarcoma (KS). Age-standardized incidence rates (ASIRs) in 2020 of HIV-attributable (epidemic) KS (A) and non–HIV-attributable (classic/endemic/iatrogenic) KS (B).

Q: The diagnosis of Kaposi Sarcoma is definitively confirmed by demonstrating nuclear positivity for [...] (also known as KSHV) via LANA-1 immunohistochemistry.
Kaposi sarcoma. Nodular Kaposi sarcoma; positive nuclear staining with an antibody to KSHV/HHV8 LANA1.
A: HHV8
Back Extra: Kaposi Sarcoma
- Clinical: Kaposi sarcoma (KS) presents as purplish cutaneous lesions that can range from small patches to large nodules, often with associated lymphoedema in the lower limbs.
- Micro: Patch-stage KS shows subtle endothelial cell proliferation with dermal collagen dissection and the promontory sign, while nodular KS exhibits fascicles of mitotically active spindled cells and slit-like spaces containing red blood cells.
- Ancillary: Kaposi sarcoma is diagnosed by detecting KSHV/HHV8 in lesional tissue using PCR, in situ hybridization, and immunohistochemical staining for LANA1, CD34, CD31, and podoplanin.
Reference Gallery:
Kaposi sarcoma. Plaque-stage Kaposi sarcoma; hyperpigmented plaques are present on the hands.
Kaposi sarcoma. Nodular Kaposi sarcoma; a large vulval tumour with ulceration.
Kaposi sarcoma. Nodular and verrucous Kaposi sarcoma; numerous nodular and hyperkeratotic lesions are present in a background of associated lymphoedema.
Kaposi sarcoma. Patch-stage Kaposi sarcoma; there is dissection of dermal collagen by a subtle vasoformative proliferation, and the promontory sign is evident.
Kaposi sarcoma. Plaque-stage Kaposi sarcoma; a more cellular proliferation, extensive erythrocytic extravasation, haemosiderin pigment deposition, and a focal mononuclear inflammatory cell infiltrate are seen.
Kaposi sarcoma. Nodular Kaposi sarcoma; there are fascicles of mitotically active spindled cells, slit-like spaces containing red blood cells, and scattered hyaline globules.
Kaposi sarcoma. Nodular Kaposi sarcoma; strongly positive immunohistochemical staining for podoplanin (recognized by the D2-40 antibody).
Kaposi sarcoma. Nodular Kaposi sarcoma; positive nuclear staining with an antibody to KSHV/HHV8 LANA1.
Kaposi sarcoma. Lymphangioma-like Kaposi sarcoma; the dermis is expanded by interanastomosing lymphangiomatous-looking channels.
Kaposi sarcoma. Anaplastic (pleomorphic) Kaposi sarcoma; there is cellular atypia, focal necrosis, and an absence of obvious vasoformative features.
Kaposi sarcoma. FNAC specimen from a nodule on the leg of a man with HIV infection; there is a loosely cohesive cluster of bland spindled cells, with altered blood present in the background.
Kaposi sarcoma (KS). Age-standardized incidence rates (ASIRs) in 2020 of HIV-attributable (epidemic) KS (A) and non–HIV-attributable (classic/endemic/iatrogenic) KS (B).

Q: Clinically and macroscopically, Lobular Capillary Haemangioma typically presents as a rapidly growing, hemorrhagic, and frequently [...] polypoid nodule.
Lobular capillary haemangioma. Ulcerated polypoid vascular lobular proliferation.
A: ulcerated
Back Extra: Lobular Capillary Haemangioma
- Clinical: Lobular capillary haemangioma presents as a rapidly growing, polypoid, haemorrhagic, and frequently ulcerated blue or red nodule.
- Micro: The lesion shows variably dilated capillaries arranged in lobules within an oedematous stroma, often with prominent inflammation.
- Ancillary: Sporadic lobular capillary haemangiomas may be associated with RAS-family and BRAF mutations, particularly the c.1799T>A p.V600E mutation.
Reference Gallery:
Lobular capillary haemangioma. Ulcerated polypoid vascular lobular proliferation.
Lobular capillary haemangioma. Small variably dilated vascular channels associated with focal inflammation and oedematous stroma.

Q: Microscopic examination of a Lobular Capillary Haemangioma classically reveals variably dilated capillaries arranged in distinct [...] within an edematous stroma, often accompanied by inflammation.
Lobular capillary haemangioma. Ulcerated polypoid vascular lobular proliferation.
Lobular capillary haemangioma. Small variably dilated vascular channels associated with focal inflammation and oedematous stroma.
A: lobules
Back Extra: Lobular Capillary Haemangioma
- Clinical: Lobular capillary haemangioma presents as a rapidly growing, polypoid, haemorrhagic, and frequently ulcerated blue or red nodule.
- Micro: The lesion shows variably dilated capillaries arranged in lobules within an oedematous stroma, often with prominent inflammation.
- Ancillary: Sporadic lobular capillary haemangiomas may be associated with RAS-family and BRAF mutations, particularly the c.1799T>A p.V600E mutation.
Reference Gallery:
Lobular capillary haemangioma. Ulcerated polypoid vascular lobular proliferation.
Lobular capillary haemangioma. Small variably dilated vascular channels associated with focal inflammation and oedematous stroma.

Q: Microscopically, Lymphangioma (superficial lymphatic malformation) features dilated, thin-walled vascular structures in the papillary dermis that are classically lined by a single [...] layer of flattened endothelial cells.
Lymphangioma (superficial lymphatic malformation). Dilated thin-walled vascular structures lined by a single discontinuous layer of flattened endothelial cells.
A: discontinuous
Back Extra: Lymphangioma (superficial lymphatic malformation)
- Clinical: Lesions appear as multiple small translucent or yellowish vesicles grouped in a plaque, often with a wart-like surface and purpuric areas.
- Micro: SLMs involve the papillary dermis and consist of dilated thin-walled vascular structures lined by a single discontinuous layer of flattened endothelial cells.
- Ancillary: Endothelial cells lining SLMs express CD31, ERG, podoplanin (D2-40), LYVE1, and PROX1.
Reference Gallery:
Lymphangioma (superficial lymphatic malformation). Dilated thin-walled vascular structures lined by a single discontinuous layer of flattened endothelial cells.

Q: Microscopically, Microvenular Hemangioma features poorly defined, elongated venule-like vascular spaces that are characteristically surrounded by a conspicuous layer of [...].
Microvenular haemangioma. Small venule-like vascular spaces, each of which is surrounded by a layer of pericytes. Infiltration of the arrector pili muscles is often seen.
A: pericytes
Back Extra: Microvenular Haemangioma
- Clinical: Microvenular haemangioma is a rare, asymptomatic, red papule or plaque that primarily affects young adults, with no sex predilection. Lesions are usually single and small, located on the trunk and extremities, especially the forearms.
- Micro: Microscopically, the lesion shows poorly defined, elongated vascular channels resembling venules, dissecting hyalinized collagen bundles. Each vessel is surrounded by a conspicuous layer of pericytes, and the endothelial cells are bland and mitotically inactive.
- Ancillary: Ancillary studies are not typically necessary for diagnosis; however, immunohistochemistry can show positivity for ERG, CD31, and CD34, with negativity for podoplanin (D2-40).
Reference Gallery:
Microvenular haemangioma. Ill-defined dermal vascular proliferation composed of numerous small elongated channels.
Microvenular haemangioma. Small venule-like vascular spaces, each of which is surrounded by a layer of pericytes. Infiltration of the arrector pili muscles is often seen.

Q: An ill-defined dermal vascular proliferation composed of numerous small, elongated venule-like channels that dissect hyalinized collagen and often infiltrate arrector pili muscles is characteristic of [...].
Microvenular haemangioma. Ill-defined dermal vascular proliferation composed of numerous small elongated channels.
Microvenular haemangioma. Small venule-like vascular spaces, each of which is surrounded by a layer of pericytes. Infiltration of the arrector pili muscles is often seen.
A: Microvenular Hemangioma
Back Extra: Microvenular Haemangioma
- Clinical: Microvenular haemangioma is a rare, asymptomatic, red papule or plaque that primarily affects young adults, with no sex predilection. Lesions are usually single and small, located on the trunk and extremities, especially the forearms.
- Micro: Microscopically, the lesion shows poorly defined, elongated vascular channels resembling venules, dissecting hyalinized collagen bundles. Each vessel is surrounded by a conspicuous layer of pericytes, and the endothelial cells are bland and mitotically inactive.
- Ancillary: Ancillary studies are not typically necessary for diagnosis; however, immunohistochemistry can show positivity for ERG, CD31, and CD34, with negativity for podoplanin (D2-40).
Reference Gallery:
Microvenular haemangioma. Ill-defined dermal vascular proliferation composed of numerous small elongated channels.
Microvenular haemangioma. Small venule-like vascular spaces, each of which is surrounded by a layer of pericytes. Infiltration of the arrector pili muscles is often seen.

Q: Microscopically, Myopericytoma is characterized by concentric, multilayered perivascular growth of myoid cells that creates a characteristic [...] appearance.
Myopericytoma. Uniform ovoid cells with concentric (onion skin–like) perivascular growth.
Myopericytoma. High-power view of onion skin–like growth around a vessel.
A: onion skin-like
Back Extra: Myopericytoma
- Clinical: Myopericytomas typically present as solitary, painless dermal or subcutaneous nodules and are most common in adults.
- Micro: Characterized by concentric, multilayered perivascular growth with eosinophilic, myoid cells and onion skin-like appearance.
- Ancillary: Most myopericytomas stain positively for α-SMA and h-caldesmon, and a subset (15%) have BRAF mutations.
Reference Gallery:
Myopericytoma. Presentation as a small, well-circumscribed subcutaneous nodule.
Myopericytoma. Uniform ovoid cells with concentric (onion skin–like) perivascular growth.
Myopericytoma. Some cases show an admixture of haemangiopericytoma-like and onion skin–like vasculature.
Myopericytoma. High-power view of onion skin–like growth around a vessel.

Q: In addition to concentric perivascular growth, Myopericytoma often shows an admixture of branching vessels that have a [...] appearance.
Myopericytoma. Some cases show an admixture of haemangiopericytoma-like and onion skin–like vasculature.
A: hemangiopericytoma-like
Back Extra: Myopericytoma
- Clinical: Myopericytomas typically present as solitary, painless dermal or subcutaneous nodules and are most common in adults.
- Micro: Characterized by concentric, multilayered perivascular growth with eosinophilic, myoid cells and onion skin-like appearance.
- Ancillary: Most myopericytomas stain positively for α-SMA and h-caldesmon, and a subset (15%) have BRAF mutations.
Reference Gallery:
Myopericytoma. Presentation as a small, well-circumscribed subcutaneous nodule.
Myopericytoma. Uniform ovoid cells with concentric (onion skin–like) perivascular growth.
Myopericytoma. Some cases show an admixture of haemangiopericytoma-like and onion skin–like vasculature.
Myopericytoma. High-power view of onion skin–like growth around a vessel.

Q: In Papillary Haemangioma, the plump endothelial cells frequently contain characteristic eosinophilic intracytoplasmic globules known as [...].
Papillary haemangioma. Intravascular papillae with collagenous cores and eosinophilic intracytoplasmic inclusions (thanatosomes).
A: thanatosomes
Back Extra: Papillary Haemangioma
- Clinical: Papillary haemangioma appears as a solitary, longstanding, bluish-red papule, commonly up to 11 mm in diameter, and is most often found in adult men on the head and neck.
- Micro: Characterized by dermal, widely dilated, thin-walled vascular channels with numerous luminal papillary projections containing capillaries lined by plump endothelial cells with intracytoplasmic eosinophilic globules (thanatosomes).
- Ancillary: Endothelial cells are positive for CD31, CD34, and ERG, and negative for lymphatic markers.
Reference Gallery:
Papillary haemangioma. Lobulated dermal vascular proliferation composed of vascular channels with papillary projections.
Papillary haemangioma. Dilated vascular channels containing papillary projections and focal thrombosis.
Papillary haemangioma. Intravascular papillae with collagenous cores and eosinophilic intracytoplasmic inclusions (thanatosomes).

Q: The defining histologic feature of Papillary Haemangioma is a dermal vascular proliferation composed of widely dilated channels containing numerous luminal [...].
Papillary haemangioma. Lobulated dermal vascular proliferation composed of vascular channels with papillary projections.
Papillary haemangioma. Dilated vascular channels containing papillary projections and focal thrombosis.
A: papillary projections
Back Extra: Papillary Haemangioma
- Clinical: Papillary haemangioma appears as a solitary, longstanding, bluish-red papule, commonly up to 11 mm in diameter, and is most often found in adult men on the head and neck.
- Micro: Characterized by dermal, widely dilated, thin-walled vascular channels with numerous luminal papillary projections containing capillaries lined by plump endothelial cells with intracytoplasmic eosinophilic globules (thanatosomes).
- Ancillary: Endothelial cells are positive for CD31, CD34, and ERG, and negative for lymphatic markers.
Reference Gallery:
Papillary haemangioma. Lobulated dermal vascular proliferation composed of vascular channels with papillary projections.
Papillary haemangioma. Dilated vascular channels containing papillary projections and focal thrombosis.
Papillary haemangioma. Intravascular papillae with collagenous cores and eosinophilic intracytoplasmic inclusions (thanatosomes).

Q: A skin biopsy revealing a dense, band-like proliferation of small-caliber blood vessels within the superficial dermis, often with an overlying hyperkeratotic and acanthotic epidermis, is the classic presentation of [...].
Poikilodermatous plaque-like haemangioma. Low-power view showing a dense proliferation of small round vessels within the superficial dermis.
Poikilodermatous plaque-like haemangioma. Small-calibre blood vessels are lined by bland endothelium. The overlying epidermis is hyperkeratotic and acanthotic.
A: Poikilodermatous Plaque-like Haemangioma
Back Extra: Poikilodermatous Plaque-like Haemangioma
- Clinical: Patients present with asymptomatic, slowly growing, erythematous or violaceous scaly plaques that are often described as poikilodermous.
- Micro: Histology shows a band-like proliferation of small-calibre blood vessels in the superficial dermis, with a concomitant loss of elastic fibres and mild lymphocytic inflammation.
- Ancillary: No specific ancillary studies are typically required for diagnosis.
Reference Gallery:
Poikilodermatous plaque-like haemangioma. Low-power view showing a dense proliferation of small round vessels within the superficial dermis.
Poikilodermatous plaque-like haemangioma. Small-calibre blood vessels are lined by bland endothelium. The overlying epidermis is hyperkeratotic and acanthotic.
Poikilodermatous plaque-like haemangioma. Absence of elastic fibres in the affected area (Van Gieson).

Q: Alongside the vascular proliferation, a characteristic histologic feature of Poikilodermatous Plaque-like Haemangioma is the localized loss of [...] in the superficial dermis.
Poikilodermatous plaque-like haemangioma. Absence of elastic fibres in the affected area (Van Gieson).
A: elastic fibers
Back Extra: Poikilodermatous Plaque-like Haemangioma
- Clinical: Patients present with asymptomatic, slowly growing, erythematous or violaceous scaly plaques that are often described as poikilodermous.
- Micro: Histology shows a band-like proliferation of small-calibre blood vessels in the superficial dermis, with a concomitant loss of elastic fibres and mild lymphocytic inflammation.
- Ancillary: No specific ancillary studies are typically required for diagnosis.
Reference Gallery:
Poikilodermatous plaque-like haemangioma. Low-power view showing a dense proliferation of small round vessels within the superficial dermis.
Poikilodermatous plaque-like haemangioma. Small-calibre blood vessels are lined by bland endothelium. The overlying epidermis is hyperkeratotic and acanthotic.
Poikilodermatous plaque-like haemangioma. Absence of elastic fibres in the affected area (Van Gieson).

Q: Histologically, [...] is a vascular tumor that presents as sheets or fascicles of atypical spindled to epithelioid cells with dense, eosinophilic cytoplasm and frequently contains admixed neutrophils.
Pseudomyogenic haemangioendothelioma. A tumour composed of sheets and fascicles of atypical spindled cells.
Pseudomyogenic haemangioendothelioma. Higher-power image of atypical spindled cells with dense eosinophilic cytoplasm, resembling rhabdomyoblasts.
Pseudomyogenic haemangioendothelioma. The tumour is composed of spindled to epithelioid cells with dense, eosinophilic cytoplasm. Note the admixed neutrophils that may be seen in about 50% of cases.
A: Pseudomyogenic Haemangioendothelioma
Back Extra: Pseudomyogenic Haemangioendothelioma
- Clinical: Pseudomyogenic haemangioendothelioma often presents as painless or painful nodules, most commonly on the lower extremities, and is more prevalent in young men.
- Micro: Histologically, the tumour is composed of sheets and fascicles of atypical spindled to epithelioid cells with dense, eosinophilic cytoplasm, and may contain admixed neutrophils in about 50% of cases.
- Ancillary: Immunohistochemistry shows positivity for keratins, FLI1, ERG, and FOSB, and the presence of FOSB rearrangements can help confirm the diagnosis.
Reference Gallery:
Pseudomyogenic haemangioendothelioma. Low-power image demonstrating infiltrative tumour involving dermis and subcutis.
Pseudomyogenic haemangioendothelioma. A tumour composed of sheets and fascicles of atypical spindled cells.
Pseudomyogenic haemangioendothelioma. Higher-power image of atypical spindled cells with dense eosinophilic cytoplasm, resembling rhabdomyoblasts.
Pseudomyogenic haemangioendothelioma. In this tumour, there were sheets of atypical epithelioid cells with abundant eosinophilic cytoplasm.
Pseudomyogenic haemangioendothelioma. Diffuse expression of keratin (AE1/AE3 clones).
Pseudomyogenic haemangioendothelioma. Diffuse expression of ERG.
Pseudomyogenic haemangioendothelioma. Cutaneous pseudomyogenic haemangioendothelioma is often associated with overlying epidermal hyperplasia.
Pseudomyogenic haemangioendothelioma. Multiple lesions on the face.
Pseudomyogenic haemangioendothelioma. A patient presenting with multiple lesions on the leg.
Pseudomyogenic haemangioendothelioma. The tumour is composed of spindled to epithelioid cells with dense, eosinophilic cytoplasm. Note the admixed neutrophils that may be seen in about 50% of cases.
Pseudomyogenic haemangioendothelioma. Nuclear immunoreactivity for FOSB can help confirm the diagnosis. Cytoplasmic immunoreactivity for FOSB is also typically present in pseudomyogenic haemangioendothelioma.

Q: In Pseudomyogenic Haemangioendothelioma, the tumor cells atypically co-express keratins and endothelial markers (e.g., ERG), and characteristically show strong nuclear immunoreactivity for [...].
Pseudomyogenic haemangioendothelioma. Diffuse expression of keratin (AE1/AE3 clones).
Pseudomyogenic haemangioendothelioma. Diffuse expression of ERG.
Pseudomyogenic haemangioendothelioma. Nuclear immunoreactivity for FOSB can help confirm the diagnosis. Cytoplasmic immunoreactivity for FOSB is also typically present in pseudomyogenic haemangioendothelioma.
A: FOSB
Back Extra: Pseudomyogenic Haemangioendothelioma
- Clinical: Pseudomyogenic haemangioendothelioma often presents as painless or painful nodules, most commonly on the lower extremities, and is more prevalent in young men.
- Micro: Histologically, the tumour is composed of sheets and fascicles of atypical spindled to epithelioid cells with dense, eosinophilic cytoplasm, and may contain admixed neutrophils in about 50% of cases.
- Ancillary: Immunohistochemistry shows positivity for keratins, FLI1, ERG, and FOSB, and the presence of FOSB rearrangements can help confirm the diagnosis.
Reference Gallery:
Pseudomyogenic haemangioendothelioma. Low-power image demonstrating infiltrative tumour involving dermis and subcutis.
Pseudomyogenic haemangioendothelioma. A tumour composed of sheets and fascicles of atypical spindled cells.
Pseudomyogenic haemangioendothelioma. Higher-power image of atypical spindled cells with dense eosinophilic cytoplasm, resembling rhabdomyoblasts.
Pseudomyogenic haemangioendothelioma. In this tumour, there were sheets of atypical epithelioid cells with abundant eosinophilic cytoplasm.
Pseudomyogenic haemangioendothelioma. Diffuse expression of keratin (AE1/AE3 clones).
Pseudomyogenic haemangioendothelioma. Diffuse expression of ERG.
Pseudomyogenic haemangioendothelioma. Cutaneous pseudomyogenic haemangioendothelioma is often associated with overlying epidermal hyperplasia.
Pseudomyogenic haemangioendothelioma. Multiple lesions on the face.
Pseudomyogenic haemangioendothelioma. A patient presenting with multiple lesions on the leg.
Pseudomyogenic haemangioendothelioma. The tumour is composed of spindled to epithelioid cells with dense, eosinophilic cytoplasm. Note the admixed neutrophils that may be seen in about 50% of cases.
Pseudomyogenic haemangioendothelioma. Nuclear immunoreactivity for FOSB can help confirm the diagnosis. Cytoplasmic immunoreactivity for FOSB is also typically present in pseudomyogenic haemangioendothelioma.

Q: The uniting histologic hallmark of the two variants of Hobnail Hemangioendotheliomas (papillary intralymphatic and retiform) is the presence of hyperchromatic endothelial cells that display a [...] morphology.
Papillary intralymphatic angioendothelioma. Intraluminal papillary tufts with a fibrotic core are a characteristic feature, lined with cells with hyperchromatic, hobnail nuclei. Note the prominent stromal lymphocytes.
Papillary intralymphatic angioendothelioma. The endothelial cells lining the dissecting channels contain hyperchromatic, hobnail nuclei.
Retiform haemangioendothelioma. Elongated vascular channels, lined by darkly staining, hobnail endothelial cells. Perivascular fibrosis and lymphoid aggregates, both common features in retiform haemangioendothelioma, are also present.
A: hobnail
Back Extra: Hobnail Hemangioendotheliomas
- Clinical: Hobnail Hemangioendotheliomas (Papillary intralymphatic angioendothelioma and Retiform haemangioendothelioma) typically present as slow-growing, red/bluish plaques or nodules, < 30 mm in size.
- Micro: Both variants are characterized by darkly staining, hobnail endothelial cells. PILA shows lymphatic channels with cavernous malformations, while RHE exhibits elongated, branching vascular channels.
- Ancillary: These lesions express pan-endothelial markers (CD31, ERG, FLI1) and lymphatic endothelial markers (podoplanin, VEGFR3, PROX1).
Reference Gallery:
Papillary intralymphatic angioendothelioma. Papillary intralymphatic angioendothelioma often contains a prominent cavernous lymphatic malformation-like component. Note the deeper irregular vascular spaces.
Papillary intralymphatic angioendothelioma. Intraluminal papillary tufts with a fibrotic core are a characteristic feature, lined with cells with hyperchromatic, hobnail nuclei. Note the prominent stromal lymphocytes.
Papillary intralymphatic angioendothelioma. The endothelial cells lining the dissecting channels contain hyperchromatic, hobnail nuclei.
Retiform haemangioendothelioma. An example occurring on the foot of a 26-year-old man. Note the elongated, branching vascular channels, reminiscent of rete testis.
Retiform haemangioendothelioma. Elongated vascular channels, lined by darkly staining, hobnail endothelial cells. Perivascular fibrosis and lymphoid aggregates, both common features in retiform haemangioendothelioma, are also present.
Retiform haemangioendothelioma. Intravascular papillary tufts are often present in retiform haemangioendothelioma, as well as in papillary intravascular angioendothelioma.

Q: The retiform variant of Hobnail Hemangioendotheliomas exhibits elongated, branching vascular channels that characteristically resemble the normal architecture of the [...].
Retiform haemangioendothelioma. An example occurring on the foot of a 26-year-old man. Note the elongated, branching vascular channels, reminiscent of rete testis.
Retiform haemangioendothelioma. Elongated vascular channels, lined by darkly staining, hobnail endothelial cells. Perivascular fibrosis and lymphoid aggregates, both common features in retiform haemangioendothelioma, are also present.
A: rete testis
Back Extra: Hobnail Hemangioendotheliomas
- Clinical: Hobnail Hemangioendotheliomas (Papillary intralymphatic angioendothelioma and Retiform haemangioendothelioma) typically present as slow-growing, red/bluish plaques or nodules, < 30 mm in size.
- Micro: Both variants are characterized by darkly staining, hobnail endothelial cells. PILA shows lymphatic channels with cavernous malformations, while RHE exhibits elongated, branching vascular channels.
- Ancillary: These lesions express pan-endothelial markers (CD31, ERG, FLI1) and lymphatic endothelial markers (podoplanin, VEGFR3, PROX1).
Reference Gallery:
Papillary intralymphatic angioendothelioma. Papillary intralymphatic angioendothelioma often contains a prominent cavernous lymphatic malformation-like component. Note the deeper irregular vascular spaces.
Papillary intralymphatic angioendothelioma. Intraluminal papillary tufts with a fibrotic core are a characteristic feature, lined with cells with hyperchromatic, hobnail nuclei. Note the prominent stromal lymphocytes.
Papillary intralymphatic angioendothelioma. The endothelial cells lining the dissecting channels contain hyperchromatic, hobnail nuclei.
Retiform haemangioendothelioma. An example occurring on the foot of a 26-year-old man. Note the elongated, branching vascular channels, reminiscent of rete testis.
Retiform haemangioendothelioma. Elongated vascular channels, lined by darkly staining, hobnail endothelial cells. Perivascular fibrosis and lymphoid aggregates, both common features in retiform haemangioendothelioma, are also present.
Retiform haemangioendothelioma. Intravascular papillary tufts are often present in retiform haemangioendothelioma, as well as in papillary intravascular angioendothelioma.

Q: The papillary intralymphatic variant of Hobnail Hemangioendotheliomas often features cavernous lymphatic malformation-like spaces containing characteristic intraluminal [...] with fibrotic cores.
Papillary intralymphatic angioendothelioma. Papillary intralymphatic angioendothelioma often contains a prominent cavernous lymphatic malformation-like component. Note the deeper irregular vascular spaces.
Papillary intralymphatic angioendothelioma. Intraluminal papillary tufts with a fibrotic core are a characteristic feature, lined with cells with hyperchromatic, hobnail nuclei. Note the prominent stromal lymphocytes.
A: papillary tufts
Back Extra: Hobnail Hemangioendotheliomas
- Clinical: Hobnail Hemangioendotheliomas (Papillary intralymphatic angioendothelioma and Retiform haemangioendothelioma) typically present as slow-growing, red/bluish plaques or nodules, < 30 mm in size.
- Micro: Both variants are characterized by darkly staining, hobnail endothelial cells. PILA shows lymphatic channels with cavernous malformations, while RHE exhibits elongated, branching vascular channels.
- Ancillary: These lesions express pan-endothelial markers (CD31, ERG, FLI1) and lymphatic endothelial markers (podoplanin, VEGFR3, PROX1).
Reference Gallery:
Papillary intralymphatic angioendothelioma. Papillary intralymphatic angioendothelioma often contains a prominent cavernous lymphatic malformation-like component. Note the deeper irregular vascular spaces.
Papillary intralymphatic angioendothelioma. Intraluminal papillary tufts with a fibrotic core are a characteristic feature, lined with cells with hyperchromatic, hobnail nuclei. Note the prominent stromal lymphocytes.
Papillary intralymphatic angioendothelioma. The endothelial cells lining the dissecting channels contain hyperchromatic, hobnail nuclei.
Retiform haemangioendothelioma. An example occurring on the foot of a 26-year-old man. Note the elongated, branching vascular channels, reminiscent of rete testis.
Retiform haemangioendothelioma. Elongated vascular channels, lined by darkly staining, hobnail endothelial cells. Perivascular fibrosis and lymphoid aggregates, both common features in retiform haemangioendothelioma, are also present.
Retiform haemangioendothelioma. Intravascular papillary tufts are often present in retiform haemangioendothelioma, as well as in papillary intravascular angioendothelioma.

Q: The irregular, dilated, thin-walled vascular channels in Sinusoidal Hemangioma characteristically impart a distinctive [...] or sinusoidal pattern on histology.
Sinusoidal haemangioma. Note the distinctive sinusoidal appearance of the vascular channels.
A: sieve-like
Back Extra: Sinusoidal Hemangioma
- Clinical: Sinusoidal hemangiomas are small, asymptomatic, well-demarcated dermal or subcutaneous bluish nodules, primarily occurring in middle-aged women.
- Micro: The lesions are lobular and well-circumscribed, composed of irregular, dilated, thin-walled vascular channels with a sinusoidal or sieve-like pattern.
- Ancillary: No specific ancillary studies are necessary for the diagnosis of sinusoidal hemangioma.
Reference Gallery:
Sinusoidal haemangioma. Note the distinctive sinusoidal appearance of the vascular channels.

Q: A lobular, well-circumscribed vascular lesion composed of irregular, thin-walled channels forming a sieve-like pattern, typically presenting as a bluish dermal or subcutaneous nodule in middle-aged women, is diagnostic of [...].
Sinusoidal haemangioma. Note the distinctive sinusoidal appearance of the vascular channels.
A: Sinusoidal Hemangioma
Back Extra: Sinusoidal Hemangioma
- Clinical: Sinusoidal hemangiomas are small, asymptomatic, well-demarcated dermal or subcutaneous bluish nodules, primarily occurring in middle-aged women.
- Micro: The lesions are lobular and well-circumscribed, composed of irregular, dilated, thin-walled vascular channels with a sinusoidal or sieve-like pattern.
- Ancillary: No specific ancillary studies are necessary for the diagnosis of sinusoidal hemangioma.
Reference Gallery:
Sinusoidal haemangioma. Note the distinctive sinusoidal appearance of the vascular channels.

Q: Microscopically, [...] is characterized by irregular, dilated, thin-walled vascular channels admixed with solid areas of bland spindle-shaped cells and vacuolated epithelioid endothelial cells.
Spindle cell haemangioma. Dilated and congested thin-walled vascular channels with spindle-shaped and vacuolated endothelial cells in the background.
Spindle cell haemangioma. Bland spindle-shaped cells, vascular channels lined by a layer of flattened endothelial cells, and aggregates of vacuolated cells.
Spindle cell haemangioma. Spindle-shaped cells and vacuolated cells with cells displaying intracytoplasmic lumina.
A: Spindle Cell Haemangioma
Back Extra: Spindle Cell Haemangioma
- Clinical: Spindle cell haemangiomas are multiple, asymptomatic bluish nodules that develop over many years and are associated with Maffucci syndrome, lymphoedema, early-onset varicose veins, and Klippel–Trénaunay syndrome.
- Micro: The lesion is characterized by irregular, dilated, thin-walled vascular channels mixed with solid areas of vacuolated epithelioid endothelial cells and bland spindle-shaped cells.
- Ancillary: Sporadic and Maffucci syndrome-associated lesions often have IDH1 p.R132C hotspot mutations and somatic alterations in 2p22.3, 2q24.3, and 14q11.2.
Reference Gallery:
Spindle cell haemangioma. Dilated and congested thin-walled vascular channels with spindle-shaped and vacuolated endothelial cells in the background.
Spindle cell haemangioma. Bland spindle-shaped cells, vascular channels lined by a layer of flattened endothelial cells, and aggregates of vacuolated cells.
Spindle cell haemangioma. Spindle-shaped cells and vacuolated cells with cells displaying intracytoplasmic lumina.
Spindle cell haemangioma. Clinical appearance during surgical removal.

Q: Clinically presenting as multiple asymptomatic bluish nodules, [...] is frequently associated with Maffucci syndrome, lymphedema, and Klippel-Trénaunay syndrome.
Spindle cell haemangioma. Clinical appearance during surgical removal.
A: Spindle Cell Haemangioma
Back Extra: Spindle Cell Haemangioma
- Clinical: Spindle cell haemangiomas are multiple, asymptomatic bluish nodules that develop over many years and are associated with Maffucci syndrome, lymphoedema, early-onset varicose veins, and Klippel–Trénaunay syndrome.
- Micro: The lesion is characterized by irregular, dilated, thin-walled vascular channels mixed with solid areas of vacuolated epithelioid endothelial cells and bland spindle-shaped cells.
- Ancillary: Sporadic and Maffucci syndrome-associated lesions often have IDH1 p.R132C hotspot mutations and somatic alterations in 2p22.3, 2q24.3, and 14q11.2.
Reference Gallery:
Spindle cell haemangioma. Dilated and congested thin-walled vascular channels with spindle-shaped and vacuolated endothelial cells in the background.
Spindle cell haemangioma. Bland spindle-shaped cells, vascular channels lined by a layer of flattened endothelial cells, and aggregates of vacuolated cells.
Spindle cell haemangioma. Spindle-shaped cells and vacuolated cells with cells displaying intracytoplasmic lumina.
Spindle cell haemangioma. Clinical appearance during surgical removal.

Q: In Tufted Hemangioma, microscopic examination classically reveals tightly packed lobules of capillaries arranged in a [...] pattern throughout the dermis.
Tufted angioma. Tightly packed small capillary lobules throughout the dermis.
A: cannonball
Back Extra: Tufted Hemangioma
- Clinical: Tufted hemangiomas are slow-growing, poorly defined macules, papules, nodules, and plaques, often seen in infants and children.
- Micro: Characterized by multiple tightly packed lobules of capillaries with a cannonball pattern and crescent-like lymphatic spaces.
- Ancillary: Genetic evidence supports a homogeneous methylation pattern, linking tufted hemangioma to kaposiform hemangioendothelioma.
Reference Gallery:
Tufted angioma. Tightly packed small capillary lobules throughout the dermis.
Tufted angioma. Small capillary lobules associated with crescent-like lymphatic spaces.

Q: A characteristic histologic finding in Tufted Hemangioma is the presence of capillary lobules associated with peripheral, [...].
Tufted angioma. Small capillary lobules associated with crescent-like lymphatic spaces.
A: crescent-like lymphatic spaces
Back Extra: Tufted Hemangioma
- Clinical: Tufted hemangiomas are slow-growing, poorly defined macules, papules, nodules, and plaques, often seen in infants and children.
- Micro: Characterized by multiple tightly packed lobules of capillaries with a cannonball pattern and crescent-like lymphatic spaces.
- Ancillary: Genetic evidence supports a homogeneous methylation pattern, linking tufted hemangioma to kaposiform hemangioendothelioma.
Reference Gallery:
Tufted angioma. Tightly packed small capillary lobules throughout the dermis.
Tufted angioma. Small capillary lobules associated with crescent-like lymphatic spaces.

Q: Histologic examination of [...] characteristically displays prominent epidermal papillomatosis and hyperkeratosis overlying dilated, congested capillaries and venules in the dermis and subcutaneous tissue.
Verrucous venous malformation. Warty changes of the epidermis associated with a superficial, deep dermal, and subcutaneous vascular proliferation.
Verrucous venous malformation. Dilated congested vascular spaces in the papillary dermis and a vascular proliferation in the dermis and subcutis.
A: Verrucous Venous Malformation
Back Extra: Verrucous Venous Malformation
- Clinical: Verrucous Venous Malformation presents as slightly raised, red to purple plaques that become more hyperkeratotic and may ulcerate, bleed, and slowly enlarge over time.
- Micro: The epidermis shows prominent acanthosis, papillomatosis, hyperkeratosis, and parakeratosis, with dilated and congested capillaries and venules in the papillary dermis and subcutaneous tissue.
- Ancillary: A somatic missense mutation in MAP3K3 has been identified in some cases of Verrucous Venous Malformation.
Reference Gallery:
Verrucous venous malformation. Warty changes of the epidermis associated with a superficial, deep dermal, and subcutaneous vascular proliferation.
Verrucous venous malformation. Dilated congested vascular spaces in the papillary dermis and a vascular proliferation in the dermis and subcutis.

Q: In Verrucous Venous Malformation, the characteristic underlying dermal and subcutaneous vascular proliferation is typically associated with reactive [...] epidermal changes, including marked acanthosis and papillomatosis.
Verrucous venous malformation. Warty changes of the epidermis associated with a superficial, deep dermal, and subcutaneous vascular proliferation.
A: warty
Back Extra: Verrucous Venous Malformation
- Clinical: Verrucous Venous Malformation presents as slightly raised, red to purple plaques that become more hyperkeratotic and may ulcerate, bleed, and slowly enlarge over time.
- Micro: The epidermis shows prominent acanthosis, papillomatosis, hyperkeratosis, and parakeratosis, with dilated and congested capillaries and venules in the papillary dermis and subcutaneous tissue.
- Ancillary: A somatic missense mutation in MAP3K3 has been identified in some cases of Verrucous Venous Malformation.
Reference Gallery:
Verrucous venous malformation. Warty changes of the epidermis associated with a superficial, deep dermal, and subcutaneous vascular proliferation.
Verrucous venous malformation. Dilated congested vascular spaces in the papillary dermis and a vascular proliferation in the dermis and subcutis.

Q: A classic histologic hallmark of Cellular Neurothekeoma is the presence of [...] of epithelioid or spindled cells with vesicular nuclei and pale eosinophilic cytoplasm, set within a dense collagenous stroma.
Cellular neurothekeoma. Scanning magnification showing a well-circumscribed dermal nodule.
Cellular neurothekeoma. Higher magnification showing nodules composed of epithelioid cells with a vesicular nucleus, small nucleolus, and pale eosinophilic cytoplasm, surrounded by dense collagenous stroma.
A: lobulated or micronodular nests
Back Extra: Cellular Neurothekeoma
- Clinical: Cellular neurothekeoma commonly occurs in children and young adults, with a female predominance, and typically presents as a solitary firm papule or nodule on the face, shoulders, or upper limbs.
- Micro: Histologically, cellular neurothekeoma is characterized by lobulated or micronodular nests of epithelioid or spindled cells with vesicular nuclei, small nucleoli, and pale eosinophilic cytoplasm, often separated by dense collagenous stroma.
- Ancillary: Immunohistochemically, cellular neurothekeoma consistently expresses CD63, NSE, PGP9.5, and S100A6, but does not express S100, GFAP, CD57, SOX10, or EMA.
Reference Gallery:
Cellular neurothekeoma. Scanning magnification showing a well-circumscribed dermal nodule.
Cellular neurothekeoma. Higher magnification showing nodules composed of epithelioid cells with a vesicular nucleus, small nucleolus, and pale eosinophilic cytoplasm, surrounded by dense collagenous stroma.
Cellular neurothekeoma. Some tumours show prominent myxoid stromal change and can mimic dermal nerve sheath myxoma.

Q: While typically presenting with a dense collagenous stroma, some Cellular Neurothekeoma tumors exhibit prominent myxoid stromal changes, making them a close morphologic mimic of [...].
Cellular neurothekeoma. Some tumours show prominent myxoid stromal change and can mimic dermal nerve sheath myxoma.
A: dermal nerve sheath myxoma
Back Extra: Cellular Neurothekeoma
- Clinical: Cellular neurothekeoma commonly occurs in children and young adults, with a female predominance, and typically presents as a solitary firm papule or nodule on the face, shoulders, or upper limbs.
- Micro: Histologically, cellular neurothekeoma is characterized by lobulated or micronodular nests of epithelioid or spindled cells with vesicular nuclei, small nucleoli, and pale eosinophilic cytoplasm, often separated by dense collagenous stroma.
- Ancillary: Immunohistochemically, cellular neurothekeoma consistently expresses CD63, NSE, PGP9.5, and S100A6, but does not express S100, GFAP, CD57, SOX10, or EMA.
Reference Gallery:
Cellular neurothekeoma. Scanning magnification showing a well-circumscribed dermal nodule.
Cellular neurothekeoma. Higher magnification showing nodules composed of epithelioid cells with a vesicular nucleus, small nucleolus, and pale eosinophilic cytoplasm, surrounded by dense collagenous stroma.
Cellular neurothekeoma. Some tumours show prominent myxoid stromal change and can mimic dermal nerve sheath myxoma.

Q: Histologically, the spindle and epithelioid tumor cells of Dermal Clear Cell Sarcoma are typically arranged in compact fascicles separated by thin strands of collagen and frequently contain characteristic [...].
Dermal clear cell sarcoma. Compact fascicles of tumour cells are present in the dermis, separated by thin strands of collagen. Some tumour cells display clear cell features.
Dermal clear cell sarcoma. Multinucleated wreath-like giant cells are present.
A: multinucleated wreath-type giant cells
Back Extra: Dermal Clear Cell Sarcoma
- Clinical: Dermal Clear Cell Sarcoma typically affects young adults in the third to fourth decade of life, often presenting as small amelanotic nodules on the extremities.
- Micro: The tumour is characterized by fascicles and nests of amelanotic spindle and epithelioid cells, often with multinucleated wreath-type giant cells and collagenous septa.
- Ancillary: Immunohistochemistry shows positivity for S100, SOX10, and melanocyte differentiation antigens, while the presence of EWSR1 gene rearrangements and EWSR1::ATF1 or EWSR1::CREB1 gene fusions helps in diagnosis.
Reference Gallery:
Dermal clear cell sarcoma. An amelanotic spindle cell tumour fills the dermis and extends into the superficial subcutis.
Dermal clear cell sarcoma. Compact fascicles of tumour cells are present in the dermis, separated by thin strands of collagen. Some tumour cells display clear cell features.
Dermal clear cell sarcoma. Multinucleated wreath-like giant cells are present.
Compound dermal clear cell sarcoma. There is an amelanotic infiltrative spindle cell tumour involving acral skin.
Compound clear cell sarcoma. Nests of tumour cells are present at the dermoepidermal junction, overlying fascicles of intradermal spindle cells, with an occasional multinucleated cell.

Q: In the compound variant of Dermal Clear Cell Sarcoma, the amelanotic spindle cell tumor involves the acral skin and uniquely exhibits nests of tumor cells at the [...], mimicking melanoma.
Compound dermal clear cell sarcoma. There is an amelanotic infiltrative spindle cell tumour involving acral skin.
Compound clear cell sarcoma. Nests of tumour cells are present at the dermoepidermal junction, overlying fascicles of intradermal spindle cells, with an occasional multinucleated cell.
A: dermoepidermal junction
Back Extra: Dermal Clear Cell Sarcoma
- Clinical: Dermal Clear Cell Sarcoma typically affects young adults in the third to fourth decade of life, often presenting as small amelanotic nodules on the extremities.
- Micro: The tumour is characterized by fascicles and nests of amelanotic spindle and epithelioid cells, often with multinucleated wreath-type giant cells and collagenous septa.
- Ancillary: Immunohistochemistry shows positivity for S100, SOX10, and melanocyte differentiation antigens, while the presence of EWSR1 gene rearrangements and EWSR1::ATF1 or EWSR1::CREB1 gene fusions helps in diagnosis.
Reference Gallery:
Dermal clear cell sarcoma. An amelanotic spindle cell tumour fills the dermis and extends into the superficial subcutis.
Dermal clear cell sarcoma. Compact fascicles of tumour cells are present in the dermis, separated by thin strands of collagen. Some tumour cells display clear cell features.
Dermal clear cell sarcoma. Multinucleated wreath-like giant cells are present.
Compound dermal clear cell sarcoma. There is an amelanotic infiltrative spindle cell tumour involving acral skin.
Compound clear cell sarcoma. Nests of tumour cells are present at the dermoepidermal junction, overlying fascicles of intradermal spindle cells, with an occasional multinucleated cell.

Q: A circumscribed, dermal spindle and epithelioid cell neoplasm that demonstrates diffuse SOX10 positivity but only patchy or variable S100 expression is highly characteristic of [TRIM11 cutaneous tumor].
CRTC1::TRIM11 cutaneous tumour. Low-power magnification shows a circumscribed, unencapsulated, dermal, spindle cell tumour.
CRTC1::TRIM11 cutaneous tumour. SOX10 immunohistochemistry shows diffuse nuclear positivity in tumour cells. Note that the tumour is dermal, circumscribed, and unencapsulated.
CRTC1::TRIM11 cutaneous tumour. S100 immunohistochemistry shows patchy, pale staining in tumour cells.
A: CRTC1
Back Extra: CRTC1::TRIM11 Cutaneous Tumour
- Clinical: CRTC1::TRIM11 Cutaneous Tumours typically present as discrete, slowly growing, skin-coloured nodules, often on the extremities or trunk, with occasional mild pain or tingling.
- Micro: The tumour is characterized by dermal-based, circumscribed nodules with spindle and epithelioid cells arranged in nests and streaming fascicles, featuring pale cytoplasm, vesicular chromatin, and prominent nucleoli.
- Ancillary: Diagnosis is confirmed by the presence of CRTC1::TRIM11 fusion, with diffuse SOX10 positivity and variable S100 expression.
Reference Gallery:
CRTC1::TRIM11 cutaneous tumour. Low-power magnification shows a circumscribed, unencapsulated, dermal, spindle cell tumour.
CRTC1::TRIM11 cutaneous tumour. Nests and short fascicles of oval cells embedded in thin fibrous strands are seen. Cells have amphophilic cytoplasm, open chromatin, and small central nucleoli.
CRTC1::TRIM11 cutaneous tumour. SOX10 immunohistochemistry shows diffuse nuclear positivity in tumour cells. Note that the tumour is dermal, circumscribed, and unencapsulated.
CRTC1::TRIM11 cutaneous tumour. S100 immunohistochemistry shows patchy, pale staining in tumour cells.
CRTC1::TRIM11 cutaneous tumour. Neoplastic cells are arranged in ill-defined nests and fascicles in a fibrillary stroma.
CRTC1::TRIM11 cutaneous tumour. Cells have pale, vacuolated cytoplasm and open to vesicular chromatin, with central, variably prominent nucleoli.
CRTC1::TRIM11 cutaneous tumour. TRIM11 immunohistochemistry. Nuclear positivity in the tumoural cells is stronger in the invasive border of the lesion. Notice the strong positivity of fibres within the dermis (usual internal control).
CRTC1::TRIM11 cutaneous tumour. The lesion is made of nests and long intersecting fascicles of spindled and epithelioid large cells with mild atypia in a fibrous background.
CRTC1::TRIM11 cutaneous tumour. Nests of large unpigmented cells are seen. Nuclei are oval or spindled and often have a large visible nucleolus; the cytoplasm is fibrillar. No mitotic activity is visible.
CRTC1::TRIM11 cutaneous tumour. An area with a higher density displaying several multinucleated small or large cells, as well as a few isolated cells with dense granular intracytoplasmic melanin pigment.

Q: Morphologically, CRTC1::TRIM11 cutaneous tumor typically presents as a dermal-based, unencapsulated nodule composed of spindle and epithelioid cells that are arranged in characteristic [...].
CRTC1::TRIM11 cutaneous tumour. Nests and short fascicles of oval cells embedded in thin fibrous strands are seen. Cells have amphophilic cytoplasm, open chromatin, and small central nucleoli.
CRTC1::TRIM11 cutaneous tumour. Neoplastic cells are arranged in ill-defined nests and fascicles in a fibrillary stroma.
CRTC1::TRIM11 cutaneous tumour. The lesion is made of nests and long intersecting fascicles of spindled and epithelioid large cells with mild atypia in a fibrous background.
A: nests and streaming fascicles
Back Extra: CRTC1::TRIM11 Cutaneous Tumour
- Clinical: CRTC1::TRIM11 Cutaneous Tumours typically present as discrete, slowly growing, skin-coloured nodules, often on the extremities or trunk, with occasional mild pain or tingling.
- Micro: The tumour is characterized by dermal-based, circumscribed nodules with spindle and epithelioid cells arranged in nests and streaming fascicles, featuring pale cytoplasm, vesicular chromatin, and prominent nucleoli.
- Ancillary: Diagnosis is confirmed by the presence of CRTC1::TRIM11 fusion, with diffuse SOX10 positivity and variable S100 expression.
Reference Gallery:
CRTC1::TRIM11 cutaneous tumour. Low-power magnification shows a circumscribed, unencapsulated, dermal, spindle cell tumour.
CRTC1::TRIM11 cutaneous tumour. Nests and short fascicles of oval cells embedded in thin fibrous strands are seen. Cells have amphophilic cytoplasm, open chromatin, and small central nucleoli.
CRTC1::TRIM11 cutaneous tumour. SOX10 immunohistochemistry shows diffuse nuclear positivity in tumour cells. Note that the tumour is dermal, circumscribed, and unencapsulated.
CRTC1::TRIM11 cutaneous tumour. S100 immunohistochemistry shows patchy, pale staining in tumour cells.
CRTC1::TRIM11 cutaneous tumour. Neoplastic cells are arranged in ill-defined nests and fascicles in a fibrillary stroma.
CRTC1::TRIM11 cutaneous tumour. Cells have pale, vacuolated cytoplasm and open to vesicular chromatin, with central, variably prominent nucleoli.
CRTC1::TRIM11 cutaneous tumour. TRIM11 immunohistochemistry. Nuclear positivity in the tumoural cells is stronger in the invasive border of the lesion. Notice the strong positivity of fibres within the dermis (usual internal control).
CRTC1::TRIM11 cutaneous tumour. The lesion is made of nests and long intersecting fascicles of spindled and epithelioid large cells with mild atypia in a fibrous background.
CRTC1::TRIM11 cutaneous tumour. Nests of large unpigmented cells are seen. Nuclei are oval or spindled and often have a large visible nucleolus; the cytoplasm is fibrillar. No mitotic activity is visible.
CRTC1::TRIM11 cutaneous tumour. An area with a higher density displaying several multinucleated small or large cells, as well as a few isolated cells with dense granular intracytoplasmic melanin pigment.

Q: In CRTC1::TRIM11 cutaneous tumor, definitive diagnosis is confirmed by identifying the underlying [TRIM11 fusion] via molecular testing or targeted nuclear immunohistochemistry.
CRTC1::TRIM11 cutaneous tumour. TRIM11 immunohistochemistry. Nuclear positivity in the tumoural cells is stronger in the invasive border of the lesion. Notice the strong positivity of fibres within the dermis (usual internal control).
A: CRTC1
Back Extra: CRTC1::TRIM11 Cutaneous Tumour
- Clinical: CRTC1::TRIM11 Cutaneous Tumours typically present as discrete, slowly growing, skin-coloured nodules, often on the extremities or trunk, with occasional mild pain or tingling.
- Micro: The tumour is characterized by dermal-based, circumscribed nodules with spindle and epithelioid cells arranged in nests and streaming fascicles, featuring pale cytoplasm, vesicular chromatin, and prominent nucleoli.
- Ancillary: Diagnosis is confirmed by the presence of CRTC1::TRIM11 fusion, with diffuse SOX10 positivity and variable S100 expression.
Reference Gallery:
CRTC1::TRIM11 cutaneous tumour. Low-power magnification shows a circumscribed, unencapsulated, dermal, spindle cell tumour.
CRTC1::TRIM11 cutaneous tumour. Nests and short fascicles of oval cells embedded in thin fibrous strands are seen. Cells have amphophilic cytoplasm, open chromatin, and small central nucleoli.
CRTC1::TRIM11 cutaneous tumour. SOX10 immunohistochemistry shows diffuse nuclear positivity in tumour cells. Note that the tumour is dermal, circumscribed, and unencapsulated.
CRTC1::TRIM11 cutaneous tumour. S100 immunohistochemistry shows patchy, pale staining in tumour cells.
CRTC1::TRIM11 cutaneous tumour. Neoplastic cells are arranged in ill-defined nests and fascicles in a fibrillary stroma.
CRTC1::TRIM11 cutaneous tumour. Cells have pale, vacuolated cytoplasm and open to vesicular chromatin, with central, variably prominent nucleoli.
CRTC1::TRIM11 cutaneous tumour. TRIM11 immunohistochemistry. Nuclear positivity in the tumoural cells is stronger in the invasive border of the lesion. Notice the strong positivity of fibres within the dermis (usual internal control).
CRTC1::TRIM11 cutaneous tumour. The lesion is made of nests and long intersecting fascicles of spindled and epithelioid large cells with mild atypia in a fibrous background.
CRTC1::TRIM11 cutaneous tumour. Nests of large unpigmented cells are seen. Nuclei are oval or spindled and often have a large visible nucleolus; the cytoplasm is fibrillar. No mitotic activity is visible.
CRTC1::TRIM11 cutaneous tumour. An area with a higher density displaying several multinucleated small or large cells, as well as a few isolated cells with dense granular intracytoplasmic melanin pigment.

Q: Classic Epithelioid Sarcoma commonly presents in acral skin with a sporotrichoid spread and histologically shows a pseudogranulomatous pattern with atypical cells palisading around foci of [...].
Classic/conventional epithelioid sarcoma. A granulomatous lesion composed of atypical epithelioid and spindled cells palisading around a focus of necrobiosis.
Classic/conventional epithelioid sarcoma. Polygonal epithelioid tumour cells with abundant eosinophilic cytoplasm and distinct cell borders.
A: necrobiosis
Back Extra: Epithelioid Sarcoma
- Clinical: Classic Epithelioid Sarcoma commonly presents as superficial, slow-growing, painless, firm nodules in acral skin, with a characteristic sporotrichoid spread.
- Micro: Classic Epithelioid Sarcoma shows a pseudogranulomatous pattern with atypical epithelioid and spindled cells palisading around foci of necrobiosis. Proximal type displays sheet-like growth of larger epithelioid cells.
- Ancillary: Loss of nuclear SMARCB1 expression is a key diagnostic feature in both subtypes of Epithelioid Sarcoma.
Reference Gallery:
Classic/conventional epithelioid sarcoma. A granulomatous lesion composed of atypical epithelioid and spindled cells palisading around a focus of necrobiosis.
Classic/conventional epithelioid sarcoma. Polygonal epithelioid tumour cells with abundant eosinophilic cytoplasm and distinct cell borders.
Classic/conventional epithelioid sarcoma. Tumour cells reveal loss of SMARCB1 nuclear expression, while endothelial and inflammatory cells show retained expression.
Proximal epithelioid sarcoma. A sheet-like proliferation of poorly differentiated rhabdoid tumour cells with pleomorphic vesicular nuclei and prominent nucleoli.

Q: A key diagnostic feature in both classic and proximal subtypes of Epithelioid Sarcoma is the loss of nuclear expression of [...] on immunohistochemistry.
Classic/conventional epithelioid sarcoma. Tumour cells reveal loss of SMARCB1 nuclear expression, while endothelial and inflammatory cells show retained expression.
A: SMARCB1
Back Extra: Epithelioid Sarcoma
- Clinical: Classic Epithelioid Sarcoma commonly presents as superficial, slow-growing, painless, firm nodules in acral skin, with a characteristic sporotrichoid spread.
- Micro: Classic Epithelioid Sarcoma shows a pseudogranulomatous pattern with atypical epithelioid and spindled cells palisading around foci of necrobiosis. Proximal type displays sheet-like growth of larger epithelioid cells.
- Ancillary: Loss of nuclear SMARCB1 expression is a key diagnostic feature in both subtypes of Epithelioid Sarcoma.
Reference Gallery:
Classic/conventional epithelioid sarcoma. A granulomatous lesion composed of atypical epithelioid and spindled cells palisading around a focus of necrobiosis.
Classic/conventional epithelioid sarcoma. Polygonal epithelioid tumour cells with abundant eosinophilic cytoplasm and distinct cell borders.
Classic/conventional epithelioid sarcoma. Tumour cells reveal loss of SMARCB1 nuclear expression, while endothelial and inflammatory cells show retained expression.
Proximal epithelioid sarcoma. A sheet-like proliferation of poorly differentiated rhabdoid tumour cells with pleomorphic vesicular nuclei and prominent nucleoli.

Q: Unlike the classic subtype, the proximal variant of Epithelioid Sarcoma characteristically displays a sheet-like growth pattern composed of larger, poorly differentiated [...] tumor cells with prominent nucleoli.
Proximal epithelioid sarcoma. A sheet-like proliferation of poorly differentiated rhabdoid tumour cells with pleomorphic vesicular nuclei and prominent nucleoli.
A: rhabdoid
Back Extra: Epithelioid Sarcoma
- Clinical: Classic Epithelioid Sarcoma commonly presents as superficial, slow-growing, painless, firm nodules in acral skin, with a characteristic sporotrichoid spread.
- Micro: Classic Epithelioid Sarcoma shows a pseudogranulomatous pattern with atypical epithelioid and spindled cells palisading around foci of necrobiosis. Proximal type displays sheet-like growth of larger epithelioid cells.
- Ancillary: Loss of nuclear SMARCB1 expression is a key diagnostic feature in both subtypes of Epithelioid Sarcoma.
Reference Gallery:
Classic/conventional epithelioid sarcoma. A granulomatous lesion composed of atypical epithelioid and spindled cells palisading around a focus of necrobiosis.
Classic/conventional epithelioid sarcoma. Polygonal epithelioid tumour cells with abundant eosinophilic cytoplasm and distinct cell borders.
Classic/conventional epithelioid sarcoma. Tumour cells reveal loss of SMARCB1 nuclear expression, while endothelial and inflammatory cells show retained expression.
Proximal epithelioid sarcoma. A sheet-like proliferation of poorly differentiated rhabdoid tumour cells with pleomorphic vesicular nuclei and prominent nucleoli.

Q: A cutaneous neoplasm demonstrating a nested or trabecular growth of cells with clear to palely eosinophilic cytoplasm arranged around a delicate capillary network, which characteristically co-expresses melanocytic (e.g., HMB45) and muscle markers, is diagnostic of a [...].
Cutaneous PEComa. The tumour cells in the dermis show a trabecular and nested growth pattern and have abundant clear or palely eosinophilic cytoplasm. Scattered multinucleated tumour cells are present.
Cutaneous PEComa. A delicate capillary network surrounds nests of epithelioid tumour cells. The tumour cells have wispy eosinophilic cytoplasm and round or oval nuclei with fine chromatin and mild pleomorphism. No mitotic activity is seen.
Cutaneous PEComa. HMB45 is the most consistently expressed marker and may show diffuse or patchy cytoplasmic positivity.
A: Perivascular Epithelioid Cell Tumor (PEComa)
Back Extra: Perivascular Epithelioid Cell Tumour (PEComa)
- Clinical: Primary cutaneous PEComas are rare and typically arise in female patients, presenting as painless cutaneous nodules, papules, or plaques, most commonly on the extremities.
- Micro: Cutaneous PEComas show a nested or trabecular architecture with perivascular排列 and tumour cells with granular, palely eosinophilic, or clear cytoplasm and round nuclei with small nucleoli.
- Ancillary: PEComas characteristically express both melanocytic markers (HMB45, melan-A, MITF) and muscle markers (SMA, desmin, caldesmon). Deletion of 16p, the location of the TSC2 gene, is a frequent finding.
Reference Gallery:
Cutaneous PEComa. The tumour cells in the dermis show a trabecular and nested growth pattern and have abundant clear or palely eosinophilic cytoplasm. Scattered multinucleated tumour cells are present.
Cutaneous PEComa. A delicate capillary network surrounds nests of epithelioid tumour cells. The tumour cells have wispy eosinophilic cytoplasm and round or oval nuclei with fine chromatin and mild pleomorphism. No mitotic activity is seen.
Cutaneous PEComa. HMB45 is the most consistently expressed marker and may show diffuse or patchy cytoplasmic positivity.

Q: Perivascular Epithelioid Cell Tumor (PEComa) has a distinctive immunohistochemical profile, typically demonstrating co-expression of smooth muscle markers (e.g., SMA, desmin) and [...] markers (e.g., HMB45, Melan-A).
Cutaneous PEComa. HMB45 is the most consistently expressed marker and may show diffuse or patchy cytoplasmic positivity.
A: melanocytic
Back Extra: Perivascular Epithelioid Cell Tumour (PEComa)
- Clinical: Primary cutaneous PEComas are rare and typically arise in female patients, presenting as painless cutaneous nodules, papules, or plaques, most commonly on the extremities.
- Micro: Cutaneous PEComas show a nested or trabecular architecture with perivascular排列 and tumour cells with granular, palely eosinophilic, or clear cytoplasm and round nuclei with small nucleoli.
- Ancillary: PEComas characteristically express both melanocytic markers (HMB45, melan-A, MITF) and muscle markers (SMA, desmin, caldesmon). Deletion of 16p, the location of the TSC2 gene, is a frequent finding.
Reference Gallery:
Cutaneous PEComa. The tumour cells in the dermis show a trabecular and nested growth pattern and have abundant clear or palely eosinophilic cytoplasm. Scattered multinucleated tumour cells are present.
Cutaneous PEComa. A delicate capillary network surrounds nests of epithelioid tumour cells. The tumour cells have wispy eosinophilic cytoplasm and round or oval nuclei with fine chromatin and mild pleomorphism. No mitotic activity is seen.
Cutaneous PEComa. HMB45 is the most consistently expressed marker and may show diffuse or patchy cytoplasmic positivity.

Q: In Carney Complex, patients often present with multiple endocrine tumors, myxomas, and spotty facial or mucosal skin pigmentation clinically termed [...].
Carney complex. Facial lentiginosis.
Carney complex. Mucosal lentiginosis.
A: lentiginosis
Back Extra: Carney Complex
- Clinical: Carney Complex (CNC) is characterized by spotty skin pigmentation, naevi, myxomatosis, secretory endocrine tumours, and pigmented schwannomas.
- Micro: Histologically, CNC-related tumours often show increased activity of catalytic subunits of PKA (PKA Cα or PKA Cβ) due to inactivation of PRKAR1A.
- Ancillary: Genetic testing for pathogenic germline mutations in PRKAR1A, PDE8B, or PDE11A confirms the diagnosis of CNC.
Reference Gallery:
Carney complex. Facial lentiginosis.
Carney complex. Mucosal lentiginosis.
Carney complex. Superficial angiomyxoma.
Carney complex. Cardiac myxoma.
Carney complex. Pigmented epithelioid melanocytoma (epithelioid blue naevus).

Q: The clinical presentation of multiple distinctive neoplasms, including superficial angiomyxomas, cardiac myxomas, and pigmented epithelioid melanocytomas (epithelioid blue nevi), is highly characteristic of the genetic syndrome [...].
Carney complex. Superficial angiomyxoma.
Carney complex. Cardiac myxoma.
Carney complex. Pigmented epithelioid melanocytoma (epithelioid blue naevus).
A: Carney Complex
Back Extra: Carney Complex
- Clinical: Carney Complex (CNC) is characterized by spotty skin pigmentation, naevi, myxomatosis, secretory endocrine tumours, and pigmented schwannomas.
- Micro: Histologically, CNC-related tumours often show increased activity of catalytic subunits of PKA (PKA Cα or PKA Cβ) due to inactivation of PRKAR1A.
- Ancillary: Genetic testing for pathogenic germline mutations in PRKAR1A, PDE8B, or PDE11A confirms the diagnosis of CNC.
Reference Gallery:
Carney complex. Facial lentiginosis.
Carney complex. Mucosal lentiginosis.
Carney complex. Superficial angiomyxoma.
Carney complex. Cardiac myxoma.
Carney complex. Pigmented epithelioid melanocytoma (epithelioid blue naevus).

Q: Muir-Torre Syndrome is defined by the association of visceral malignancies (e.g., colonic adenocarcinomas) with characteristic cutaneous neoplasms, most notably keratoacanthomas and [...].
Sebaceous adenoma in a patient with Muir–Torre syndrome. Scanning magnification shows centrally cystic architecture in a sebaceous adenoma from a patient with Muir–Torre syndrome.
A: sebaceous adenomas
Back Extra: Muir-Torre Syndrome
- Clinical: Patients with Muir-Torre Syndrome (MTS) often develop cutaneous neoplasms, particularly sebaceous adenomas and keratoacanthomas, and visceral malignancies, especially colonic adenocarcinomas.
- Micro: Histopathological features of sebaceous adenomas in MTS include centrally cystic architecture and characteristic immunohistochemical staining patterns.
- Ancillary: Immunohistochemistry for MLH1, PMS2, MSH2, and MSH6 can help identify deficient mismatch repair (MMR) proteins, which is a key diagnostic feature of MTS.
Reference Gallery:
Sebaceous adenoma in a patient with Muir–Torre syndrome. Scanning magnification shows centrally cystic architecture in a sebaceous adenoma from a patient with Muir–Torre syndrome.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Preserved expression of MLH1 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Preserved expression of PMS2 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Deficient expression of MSH2 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Deficient expression of MSH6 by immunohistochemistry.

Q: At scanning magnification, the sebaceous adenomas associated with Muir-Torre Syndrome frequently display a characteristic [...] architecture.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Scanning magnification shows centrally cystic architecture in a sebaceous adenoma from a patient with Muir–Torre syndrome.
A: centrally cystic
Back Extra: Muir-Torre Syndrome
- Clinical: Patients with Muir-Torre Syndrome (MTS) often develop cutaneous neoplasms, particularly sebaceous adenomas and keratoacanthomas, and visceral malignancies, especially colonic adenocarcinomas.
- Micro: Histopathological features of sebaceous adenomas in MTS include centrally cystic architecture and characteristic immunohistochemical staining patterns.
- Ancillary: Immunohistochemistry for MLH1, PMS2, MSH2, and MSH6 can help identify deficient mismatch repair (MMR) proteins, which is a key diagnostic feature of MTS.
Reference Gallery:
Sebaceous adenoma in a patient with Muir–Torre syndrome. Scanning magnification shows centrally cystic architecture in a sebaceous adenoma from a patient with Muir–Torre syndrome.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Preserved expression of MLH1 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Preserved expression of PMS2 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Deficient expression of MSH2 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Deficient expression of MSH6 by immunohistochemistry.

Q: The hallmark diagnostic feature of Muir-Torre Syndrome is a deficiency in [...] proteins, which is frequently demonstrated by immunohistochemical loss of markers like MSH2 and MSH6.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Preserved expression of MLH1 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Preserved expression of PMS2 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Deficient expression of MSH2 by immunohistochemistry.
A: mismatch repair (MMR)
Back Extra: Muir-Torre Syndrome
- Clinical: Patients with Muir-Torre Syndrome (MTS) often develop cutaneous neoplasms, particularly sebaceous adenomas and keratoacanthomas, and visceral malignancies, especially colonic adenocarcinomas.
- Micro: Histopathological features of sebaceous adenomas in MTS include centrally cystic architecture and characteristic immunohistochemical staining patterns.
- Ancillary: Immunohistochemistry for MLH1, PMS2, MSH2, and MSH6 can help identify deficient mismatch repair (MMR) proteins, which is a key diagnostic feature of MTS.
Reference Gallery:
Sebaceous adenoma in a patient with Muir–Torre syndrome. Scanning magnification shows centrally cystic architecture in a sebaceous adenoma from a patient with Muir–Torre syndrome.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Preserved expression of MLH1 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Preserved expression of PMS2 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Deficient expression of MSH2 by immunohistochemistry.
Sebaceous adenoma in a patient with Muir–Torre syndrome. Deficient expression of MSH6 by immunohistochemistry.

Q: Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)—which classically presents with multiple basal cell carcinomas, jaw cysts, and characteristic skeletal abnormalities—is most frequently caused by a germline mutation in the [...] gene.
Figure showing characteristic skeletal abnormalities in NBCCS.
A: PTCH1
Back Extra: Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
- Clinical: Multiple basal cell carcinomas (BCCs) and jaw odontogenic keratocysts (OKCs) are the most frequent manifestations.
- Micro: NBCCS-associated BCCs show characteristic basaloid neoplastic cells with peripheral palisading and stromal mucin deposition.
- Ancillary: Comprehensive mutation analysis of the PTCH1 and SUFU genes by DNA sequencing and MLPA identifies most NBCCS-related pathogenic variants.
Reference Gallery:
Figure showing characteristic skeletal abnormalities in NBCCS.

Q: In Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome), patients classically develop characteristic skeletal abnormalities, multiple basal cell carcinomas, and cystic jaw lesions known as [...].
Figure showing characteristic skeletal abnormalities in NBCCS.
A: odontogenic keratocysts
Back Extra: Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
- Clinical: Multiple basal cell carcinomas (BCCs) and jaw odontogenic keratocysts (OKCs) are the most frequent manifestations.
- Micro: NBCCS-associated BCCs show characteristic basaloid neoplastic cells with peripheral palisading and stromal mucin deposition.
- Ancillary: Comprehensive mutation analysis of the PTCH1 and SUFU genes by DNA sequencing and MLPA identifies most NBCCS-related pathogenic variants.
Reference Gallery:
Figure showing characteristic skeletal abnormalities in NBCCS.