Title: WHO / HN
Tags: HN::Salivary_Gland::Malignant_Tumor HN::Salivary_Gland::Benign_Tumor HN::Heme::B_Cell HN::Odontogenic_Maxillofacial::Jaw_Cyst HN::Ear_Temporal_Bone::Middle_Inner_Ear HN::Sinonasal::Carcinoma HN::Odontogenic_Maxillofacial::Benign_Epithelial HN::Larynx_Hypopharynx_Trachea::Carcinoma HN::Odontogenic_Maxillofacial::Malignant HN::Ear_Temporal_Bone::External_Auditory_Canal HN::Odontogenic_Maxillofacial::Benign_Bone_Cartilage HN::Soft_Tissue::Vascular HN::Heme::Histiocytic_Dendritic

Q: Clinically and radiologically, Ceruminous Adenocarcinoma typically presents as a destructive soft-tissue mass filling the [...], often causing otalgia and hearing changes.
Ear ceruminous adenocarcinoma. A soft tissue–density mass (arrow) is noted filling the right external auditory canal in this T2-weighted axial image.
Ceruminous adenocarcinoma. This macroscopic resection sample demonstrates infiltration of the soft tissues and bone by the neoplasm.
A: external auditory canal
Q: Ceruminous Adenocarcinoma
- Clinical: Patients with [...] commonly present with otalgia, an external auditory canal mass, and hearing changes, with fullness, discharge, and bleeding being less frequent.
- Micro: [...] is characterized by complex architecture with back-to-back glands, pleomorphic cells, and mitotic figures.
- Ancillary: Immunohistochemistry in [...] may show CD117 highlighting luminal cells, aiding in the diagnosis.
Reference Gallery:
Ear ceruminous adenocarcinoma. A soft tissue–density mass (arrow) is noted filling the right external auditory canal in this T2-weighted axial image.
Ear ceruminous adenocarcinoma. Low-power view demonstrates a destructively invasive epithelial neoplasm with complex architecture and cystic change. Ceruminous glands are at the periphery.
Ear ceruminous adenocarcinoma. Native ceruminous glands are present (left), and a complex glandular neoplasm is noted infiltrating into the stroma. Back-to-back glands, luminal papillae, and desmoplastic stroma are seen.
Ear ceruminous adenocarcinoma. The cyst is lined by a highly pleomorphic epithelial proliferation associated with necrosis, a finding not seen in ceruminous adenomas.
Ear ceruminous adenocarcinoma. Complex back-to-back architecture with pleomorphic cells that have an increased N:C ratio is a feature of carcinoma. Note the mitotic figures.
Ear ceruminous adenocarcinoma. A Roman-bridge pattern of growth is seen in this carcinoma, with apocrine surface blebs. Mitotic figures are present.
Ear ceruminous adenoid cystic carcinoma. Native ceruminous glands (far left) confirm the site of the development of this ceruminous adenoid cystic carcinoma. There is well-developed reduplicated basement membrane, epithelial-stromal clefting, and perineural invasion (centre right).
Ear ceruminous adenoid cystic carcinoma. This carcinoma demonstrates perineural invasion (left) and tumour necrosis (right), features not seen in benign lesions. A cribriform pattern is prominent.
Ear ceruminous adenoid cystic carcinoma. Native ceruminous glands show yellow-brown cytoplasmic pigment (left), whereas the neoplastic cells lack this finding. Glycosaminoglycan material and basement membrane material are noted in the carcinoma.
Ear ceruminous adenoid cystic carcinoma. Native ceruminous glands (lower field) are seen immediately adjacent to islands of adenoid cystic carcinoma. There are small ductal groups surrounded by peg-shaped, hyperchromatic nuclei.
Ceruminous adenocarcinoma. This macroscopic resection sample demonstrates infiltration of the soft tissues and bone by the neoplasm.
A: ceruminous adenocarcinoma; Ceruminous adenocarcinoma; ceruminous adenocarcinoma

Q: Microscopically, Ceruminous Adenocarcinoma demonstrates a destructively invasive, complex glandular architecture featuring characteristic [...] glands, pleomorphic cells, and frequent mitotic figures.
Ear ceruminous adenocarcinoma. Native ceruminous glands are present (left), and a complex glandular neoplasm is noted infiltrating into the stroma. Back-to-back glands, luminal papillae, and desmoplastic stroma are seen.
Ear ceruminous adenocarcinoma. Complex back-to-back architecture with pleomorphic cells that have an increased N:C ratio is a feature of carcinoma. Note the mitotic figures.
A: back-to-back
Q: Ceruminous Adenocarcinoma
- Clinical: Patients with [...] commonly present with otalgia, an external auditory canal mass, and hearing changes, with fullness, discharge, and bleeding being less frequent.
- Micro: [...] is characterized by complex architecture with back-to-back glands, pleomorphic cells, and mitotic figures.
- Ancillary: Immunohistochemistry in [...] may show CD117 highlighting luminal cells, aiding in the diagnosis.
Reference Gallery:
Ear ceruminous adenocarcinoma. A soft tissue–density mass (arrow) is noted filling the right external auditory canal in this T2-weighted axial image.
Ear ceruminous adenocarcinoma. Low-power view demonstrates a destructively invasive epithelial neoplasm with complex architecture and cystic change. Ceruminous glands are at the periphery.
Ear ceruminous adenocarcinoma. Native ceruminous glands are present (left), and a complex glandular neoplasm is noted infiltrating into the stroma. Back-to-back glands, luminal papillae, and desmoplastic stroma are seen.
Ear ceruminous adenocarcinoma. The cyst is lined by a highly pleomorphic epithelial proliferation associated with necrosis, a finding not seen in ceruminous adenomas.
Ear ceruminous adenocarcinoma. Complex back-to-back architecture with pleomorphic cells that have an increased N:C ratio is a feature of carcinoma. Note the mitotic figures.
Ear ceruminous adenocarcinoma. A Roman-bridge pattern of growth is seen in this carcinoma, with apocrine surface blebs. Mitotic figures are present.
Ear ceruminous adenoid cystic carcinoma. Native ceruminous glands (far left) confirm the site of the development of this ceruminous adenoid cystic carcinoma. There is well-developed reduplicated basement membrane, epithelial-stromal clefting, and perineural invasion (centre right).
Ear ceruminous adenoid cystic carcinoma. This carcinoma demonstrates perineural invasion (left) and tumour necrosis (right), features not seen in benign lesions. A cribriform pattern is prominent.
Ear ceruminous adenoid cystic carcinoma. Native ceruminous glands show yellow-brown cytoplasmic pigment (left), whereas the neoplastic cells lack this finding. Glycosaminoglycan material and basement membrane material are noted in the carcinoma.
Ear ceruminous adenoid cystic carcinoma. Native ceruminous glands (lower field) are seen immediately adjacent to islands of adenoid cystic carcinoma. There are small ductal groups surrounded by peg-shaped, hyperchromatic nuclei.
Ceruminous adenocarcinoma. This macroscopic resection sample demonstrates infiltration of the soft tissues and bone by the neoplasm.
A: ceruminous adenocarcinoma; Ceruminous adenocarcinoma; ceruminous adenocarcinoma

Q: A key microscopic feature that distinguishes Ceruminous Adenocarcinoma from a benign ceruminous adenoma is the presence of marked cytologic pleomorphism, increased mitotic activity, and tumor [...].
Ear ceruminous adenocarcinoma. The cyst is lined by a highly pleomorphic epithelial proliferation associated with necrosis, a finding not seen in ceruminous adenomas.
A: necrosis
Q: Ceruminous Adenocarcinoma
- Clinical: Patients with [...] commonly present with otalgia, an external auditory canal mass, and hearing changes, with fullness, discharge, and bleeding being less frequent.
- Micro: [...] is characterized by complex architecture with back-to-back glands, pleomorphic cells, and mitotic figures.
- Ancillary: Immunohistochemistry in [...] may show CD117 highlighting luminal cells, aiding in the diagnosis.
Reference Gallery:
Ear ceruminous adenocarcinoma. A soft tissue–density mass (arrow) is noted filling the right external auditory canal in this T2-weighted axial image.
Ear ceruminous adenocarcinoma. Low-power view demonstrates a destructively invasive epithelial neoplasm with complex architecture and cystic change. Ceruminous glands are at the periphery.
Ear ceruminous adenocarcinoma. Native ceruminous glands are present (left), and a complex glandular neoplasm is noted infiltrating into the stroma. Back-to-back glands, luminal papillae, and desmoplastic stroma are seen.
Ear ceruminous adenocarcinoma. The cyst is lined by a highly pleomorphic epithelial proliferation associated with necrosis, a finding not seen in ceruminous adenomas.
Ear ceruminous adenocarcinoma. Complex back-to-back architecture with pleomorphic cells that have an increased N:C ratio is a feature of carcinoma. Note the mitotic figures.
Ear ceruminous adenocarcinoma. A Roman-bridge pattern of growth is seen in this carcinoma, with apocrine surface blebs. Mitotic figures are present.
Ear ceruminous adenoid cystic carcinoma. Native ceruminous glands (far left) confirm the site of the development of this ceruminous adenoid cystic carcinoma. There is well-developed reduplicated basement membrane, epithelial-stromal clefting, and perineural invasion (centre right).
Ear ceruminous adenoid cystic carcinoma. This carcinoma demonstrates perineural invasion (left) and tumour necrosis (right), features not seen in benign lesions. A cribriform pattern is prominent.
Ear ceruminous adenoid cystic carcinoma. Native ceruminous glands show yellow-brown cytoplasmic pigment (left), whereas the neoplastic cells lack this finding. Glycosaminoglycan material and basement membrane material are noted in the carcinoma.
Ear ceruminous adenoid cystic carcinoma. Native ceruminous glands (lower field) are seen immediately adjacent to islands of adenoid cystic carcinoma. There are small ductal groups surrounded by peg-shaped, hyperchromatic nuclei.
Ceruminous adenocarcinoma. This macroscopic resection sample demonstrates infiltration of the soft tissues and bone by the neoplasm.
A: ceruminous adenocarcinoma; Ceruminous adenocarcinoma; ceruminous adenocarcinoma

Q: A diagnostic microscopic feature of ceruminous adenoma is the presence of intracytoplasmic [...] granules within the neoplastic cells.
Ear ceruminous adenoma. One of the diagnostic features of benign ceruminous neoplasms is the presence of intracytoplasmic yellow-brown pigment granules (arrows).
A: yellow-brown pigment
Back Extra: Ceruminous Adenoma
- Clinical: Ceruminous adenomas typically present as a mass in the external auditory canal with intact tympanic membrane, causing symptoms such as conductive hearing loss, otorrhoea, and otalgia.
- Micro: The neoplasm is characterized by a biphasic pattern with inner luminal cells showing apocrine change and outer basal/myoepithelial cells. Intracytoplasmic yellow-brown pigment granules are a diagnostic feature.
- Ancillary: Immunohistochemistry shows strong and diffuse reactivity for pancytokeratin, CK7, EMA, and KIT (CD117) in luminal cells, and p63 and CK5/6 in basal cells.
Reference Gallery:
Ear ceruminous adenoma. Axial CT demonstrates a well-circumscribed mass within the external auditory canal (arrow).
Ear ceruminous adenoma. Below an intact squamous epithelium, a biphasic neoplastic proliferation is noted. The inner luminal cells have abundant eosinophilic cytoplasm.
Ear ceruminous adenoma. A biphasic neoplastic proliferation shows well-developed basement membrane around the neoplastic groups. The inner luminal cells display decapitation apocrine secretions.
Ear ceruminous adenoma. A more solid appearance may be seen in some tumours, although the biphasic appearance is still easily identified.
Ear ceruminous adenoma. A well-developed basal layer subtends the luminal cells, the latter showing abundant granular eosinophilic cytoplasm with apocrine change. Pleomorphism is not identified.
Ear ceruminous adenoma. One of the diagnostic features of benign ceruminous neoplasms is the presence of intracytoplasmic yellow-brown pigment granules (arrows).
Ear ceruminous pleomorphic adenoma. A ceruminous pleomorphic adenoma shows the characteristic features of pleomorphic adenoma, while ceruminous differentiation is seen at the periphery.
Ear ceruminous adenoma. The basal cells of ceruminous adenoma can be highlighted by p63 immunohistochemistry.
Ear ceruminous adenoma. The basal cells of ceruminous adenoma can be highlighted by CK5/6 immunohistochemistry.

Q: Ceruminous adenoma characteristically displays a biphasic histologic pattern, with the inner luminal cells demonstrating [...] change and decapitation secretions.
Ear ceruminous adenoma. A biphasic neoplastic proliferation shows well-developed basement membrane around the neoplastic groups. The inner luminal cells display decapitation apocrine secretions.
Ear ceruminous adenoma. A well-developed basal layer subtends the luminal cells, the latter showing abundant granular eosinophilic cytoplasm with apocrine change. Pleomorphism is not identified.
A: apocrine
Back Extra: Ceruminous Adenoma
- Clinical: Ceruminous adenomas typically present as a mass in the external auditory canal with intact tympanic membrane, causing symptoms such as conductive hearing loss, otorrhoea, and otalgia.
- Micro: The neoplasm is characterized by a biphasic pattern with inner luminal cells showing apocrine change and outer basal/myoepithelial cells. Intracytoplasmic yellow-brown pigment granules are a diagnostic feature.
- Ancillary: Immunohistochemistry shows strong and diffuse reactivity for pancytokeratin, CK7, EMA, and KIT (CD117) in luminal cells, and p63 and CK5/6 in basal cells.
Reference Gallery:
Ear ceruminous adenoma. Axial CT demonstrates a well-circumscribed mass within the external auditory canal (arrow).
Ear ceruminous adenoma. Below an intact squamous epithelium, a biphasic neoplastic proliferation is noted. The inner luminal cells have abundant eosinophilic cytoplasm.
Ear ceruminous adenoma. A biphasic neoplastic proliferation shows well-developed basement membrane around the neoplastic groups. The inner luminal cells display decapitation apocrine secretions.
Ear ceruminous adenoma. A more solid appearance may be seen in some tumours, although the biphasic appearance is still easily identified.
Ear ceruminous adenoma. A well-developed basal layer subtends the luminal cells, the latter showing abundant granular eosinophilic cytoplasm with apocrine change. Pleomorphism is not identified.
Ear ceruminous adenoma. One of the diagnostic features of benign ceruminous neoplasms is the presence of intracytoplasmic yellow-brown pigment granules (arrows).
Ear ceruminous pleomorphic adenoma. A ceruminous pleomorphic adenoma shows the characteristic features of pleomorphic adenoma, while ceruminous differentiation is seen at the periphery.
Ear ceruminous adenoma. The basal cells of ceruminous adenoma can be highlighted by p63 immunohistochemistry.
Ear ceruminous adenoma. The basal cells of ceruminous adenoma can be highlighted by CK5/6 immunohistochemistry.

Q: In a ceruminous adenoma, the outer basal (myoepithelial) cells are characteristically highlighted by CK5/6 and the immunohistochemical marker [...].
Ear ceruminous adenoma. The basal cells of ceruminous adenoma can be highlighted by p63 immunohistochemistry.
Ear ceruminous adenoma. The basal cells of ceruminous adenoma can be highlighted by CK5/6 immunohistochemistry.
A: p63
Back Extra: Ceruminous Adenoma
- Clinical: Ceruminous adenomas typically present as a mass in the external auditory canal with intact tympanic membrane, causing symptoms such as conductive hearing loss, otorrhoea, and otalgia.
- Micro: The neoplasm is characterized by a biphasic pattern with inner luminal cells showing apocrine change and outer basal/myoepithelial cells. Intracytoplasmic yellow-brown pigment granules are a diagnostic feature.
- Ancillary: Immunohistochemistry shows strong and diffuse reactivity for pancytokeratin, CK7, EMA, and KIT (CD117) in luminal cells, and p63 and CK5/6 in basal cells.
Reference Gallery:
Ear ceruminous adenoma. Axial CT demonstrates a well-circumscribed mass within the external auditory canal (arrow).
Ear ceruminous adenoma. Below an intact squamous epithelium, a biphasic neoplastic proliferation is noted. The inner luminal cells have abundant eosinophilic cytoplasm.
Ear ceruminous adenoma. A biphasic neoplastic proliferation shows well-developed basement membrane around the neoplastic groups. The inner luminal cells display decapitation apocrine secretions.
Ear ceruminous adenoma. A more solid appearance may be seen in some tumours, although the biphasic appearance is still easily identified.
Ear ceruminous adenoma. A well-developed basal layer subtends the luminal cells, the latter showing abundant granular eosinophilic cytoplasm with apocrine change. Pleomorphism is not identified.
Ear ceruminous adenoma. One of the diagnostic features of benign ceruminous neoplasms is the presence of intracytoplasmic yellow-brown pigment granules (arrows).
Ear ceruminous pleomorphic adenoma. A ceruminous pleomorphic adenoma shows the characteristic features of pleomorphic adenoma, while ceruminous differentiation is seen at the periphery.
Ear ceruminous adenoma. The basal cells of ceruminous adenoma can be highlighted by p63 immunohistochemistry.
Ear ceruminous adenoma. The basal cells of ceruminous adenoma can be highlighted by CK5/6 immunohistochemistry.

Q: [...] classically presents clinically as an intensely painful nodule with a small, cup-shaped central crater on the helix or antihelix of the external ear.
Ear chondrodermatitis nodularis chronica helicis. A clinical photograph demonstrating a small, cup-shaped central crater affecting the helix of a male patient.
A: Chondrodermatitis nodularis chronica helicis
Back Extra: Chondrodermatitis nodularis chronica helicis
- Clinical: Patients present with an intensely painful nodule on the helix or antihelix of the external ear, typically nocturnal and exacerbated by ear pressure.
- Micro: Central cup-shaped crater filled with necrotic debris, fibrin, and inflammatory cells, surrounded by acanthotic epithelium with acute inflammation.
- Ancillary: No specific ancillary studies are required for diagnosis.
Reference Gallery:
Ear chondrodermatitis nodularis chronica helicis. Central ulceration down to the cartilage is surrounded by a hyperplastic squamous epithelium. Note the adjacent solar elastosis.
Ear chondrodermatitis nodularis chronica helicis. Fibrinoid-type necrotic debris extends down to the ear cartilage. There is adjacent granulation-type tissue and hyperplastic squamous epithelium.
Ear chondrodermatitis nodularis chronica helicis. Biopsies are frequently superficial, with areas of hyperkeratosis and scale crust. Deeper and additional levels or deeper sections generally aid in diagnosis.
Ear chondrodermatitis nodularis chronica helicis. A clinical photograph demonstrating a small, cup-shaped central crater affecting the helix of a male patient.

Q: Chondrodermatitis nodularis chronica helicis is microscopically characterized by a central cup-shaped crater filled with necrotic debris and fibrin that extends deep to involve the underlying [...].
Ear chondrodermatitis nodularis chronica helicis. Central ulceration down to the cartilage is surrounded by a hyperplastic squamous epithelium. Note the adjacent solar elastosis.
Ear chondrodermatitis nodularis chronica helicis. Fibrinoid-type necrotic debris extends down to the ear cartilage. There is adjacent granulation-type tissue and hyperplastic squamous epithelium.
A: cartilage
Back Extra: Chondrodermatitis nodularis chronica helicis
- Clinical: Patients present with an intensely painful nodule on the helix or antihelix of the external ear, typically nocturnal and exacerbated by ear pressure.
- Micro: Central cup-shaped crater filled with necrotic debris, fibrin, and inflammatory cells, surrounded by acanthotic epithelium with acute inflammation.
- Ancillary: No specific ancillary studies are required for diagnosis.
Reference Gallery:
Ear chondrodermatitis nodularis chronica helicis. Central ulceration down to the cartilage is surrounded by a hyperplastic squamous epithelium. Note the adjacent solar elastosis.
Ear chondrodermatitis nodularis chronica helicis. Fibrinoid-type necrotic debris extends down to the ear cartilage. There is adjacent granulation-type tissue and hyperplastic squamous epithelium.
Ear chondrodermatitis nodularis chronica helicis. Biopsies are frequently superficial, with areas of hyperkeratosis and scale crust. Deeper and additional levels or deeper sections generally aid in diagnosis.
Ear chondrodermatitis nodularis chronica helicis. A clinical photograph demonstrating a small, cup-shaped central crater affecting the helix of a male patient.

Q: Microscopically, Cystic Chondromalacia is characterized by a central cleft within the cartilaginous plate that lacks an epithelial lining, making it a [...].
Ear cystic chondromalacia. The cartilage is splayed by an area of central degeneration, filled with blood and granulation tissue.
Ear cystic chondromalacia. A cleft is noted within the cartilage, where mucinous material may be seen.
A: pseudocyst
Back Extra: Cystic Chondromalacia
- Clinical: Patients usually present with a unilateral, fusiform, painless, slightly fluctuant swelling. Lesions present rapidly (< 12 weeks) and lack overlying skin changes.
- Micro: The cartilaginous plate contains a central cleft without epithelium (pseudocyst), associated with fibrous tissue, granulation tissue, and mucoid material.
- Ancillary: Fine needle aspiration (FNA) shows acellular smears of granular proteinaceous material, and fluid LDH levels may support the diagnosis.
Reference Gallery:
Ear cystic chondromalacia. A clinical photograph of the left ear demonstrates a region of fusiform swelling along the scapha below the helix.
Ear cystic chondromalacia. The cartilage is splayed by an area of central degeneration, filled with blood and granulation tissue.
Ear cystic chondromalacia. Frequently, a deroofing of the lesion will be performed clinically, with only the outer cartilage plate and some associated fibrosis identified.
Ear cystic chondromalacia. Higher-magnification view shows disrupted cartilage plates with the central area degenerated, with fibrin, organizing thrombus, fibrosis, and granulation-type tissue. Note the central location of the findings.
Ear cystic chondromalacia. A cleft is noted within the cartilage, where mucinous material may be seen.

Q: Clinically, Cystic Chondromalacia typically presents as a rapid-onset, unilateral, painless, fusiform swelling of the ear that classically lacks overlying [...].
Ear cystic chondromalacia. A clinical photograph of the left ear demonstrates a region of fusiform swelling along the scapha below the helix.
A: skin changes
Back Extra: Cystic Chondromalacia
- Clinical: Patients usually present with a unilateral, fusiform, painless, slightly fluctuant swelling. Lesions present rapidly (< 12 weeks) and lack overlying skin changes.
- Micro: The cartilaginous plate contains a central cleft without epithelium (pseudocyst), associated with fibrous tissue, granulation tissue, and mucoid material.
- Ancillary: Fine needle aspiration (FNA) shows acellular smears of granular proteinaceous material, and fluid LDH levels may support the diagnosis.
Reference Gallery:
Ear cystic chondromalacia. A clinical photograph of the left ear demonstrates a region of fusiform swelling along the scapha below the helix.
Ear cystic chondromalacia. The cartilage is splayed by an area of central degeneration, filled with blood and granulation tissue.
Ear cystic chondromalacia. Frequently, a deroofing of the lesion will be performed clinically, with only the outer cartilage plate and some associated fibrosis identified.
Ear cystic chondromalacia. Higher-magnification view shows disrupted cartilage plates with the central area degenerated, with fibrin, organizing thrombus, fibrosis, and granulation-type tissue. Note the central location of the findings.
Ear cystic chondromalacia. A cleft is noted within the cartilage, where mucinous material may be seen.

Q: High-power histological evaluation of Cystic Chondromalacia reveals a central zone of cartilaginous degeneration that is often filled with mucinous material, fibrin, blood, and [...] tissue.
Ear cystic chondromalacia. Higher-magnification view shows disrupted cartilage plates with the central area degenerated, with fibrin, organizing thrombus, fibrosis, and granulation-type tissue. Note the central location of the findings.
A: granulation
Back Extra: Cystic Chondromalacia
- Clinical: Patients usually present with a unilateral, fusiform, painless, slightly fluctuant swelling. Lesions present rapidly (< 12 weeks) and lack overlying skin changes.
- Micro: The cartilaginous plate contains a central cleft without epithelium (pseudocyst), associated with fibrous tissue, granulation tissue, and mucoid material.
- Ancillary: Fine needle aspiration (FNA) shows acellular smears of granular proteinaceous material, and fluid LDH levels may support the diagnosis.
Reference Gallery:
Ear cystic chondromalacia. A clinical photograph of the left ear demonstrates a region of fusiform swelling along the scapha below the helix.
Ear cystic chondromalacia. The cartilage is splayed by an area of central degeneration, filled with blood and granulation tissue.
Ear cystic chondromalacia. Frequently, a deroofing of the lesion will be performed clinically, with only the outer cartilage plate and some associated fibrosis identified.
Ear cystic chondromalacia. Higher-magnification view shows disrupted cartilage plates with the central area degenerated, with fibrin, organizing thrombus, fibrosis, and granulation-type tissue. Note the central location of the findings.
Ear cystic chondromalacia. A cleft is noted within the cartilage, where mucinous material may be seen.

Q: Histologically, Exostosis (osteoma) of the ear is composed of dense [...] with thick, anastomosing trabeculae and absent marrow spaces located beneath an intact squamous epithelium.
Exostosis. This ear exostosis demonstrates thick trabeculae of bone beneath an intact squamous epithelium.
Exostosis. The bone is dense and thick, identified beneath an intact squamous epithelium. If on a pedicle, osteoma may be used as the diagnosis.
Exostosis. This high-power image demonstrates lamellar bone with thick, anastomosing trabeculae with reversal lines.
A: lamellar bone
Back Extra: Exostosis (osteoma) of the ear
- Clinical: Patients with exostoses of the external auditory canal (EAC) and middle ear are generally asymptomatic, but can present with conductive hearing loss, otitis externa, otalgia, and cerumen impaction.
- Micro: Histologically, exostoses are composed of lamellar bone with anastomosing trabeculae and absent marrow spaces.
- Ancillary: High-resolution CT is the best modality for assessing exostoses, showing bilateral, broad-based, convex thickenings of cortical bone.
Reference Gallery:
Exostosis. This ear exostosis demonstrates thick trabeculae of bone beneath an intact squamous epithelium.
Exostosis. The bone is dense and thick, identified beneath an intact squamous epithelium. If on a pedicle, osteoma may be used as the diagnosis.
Exostosis. This high-power image demonstrates lamellar bone with thick, anastomosing trabeculae with reversal lines.
Ear osteoma. Axial CT showing an osteoma in the lateral aspect of the left external auditory canal, with a soft tissue plug lying medial in the meatus.
Bilateral external auditory canal exostoses. High-resolution CT shows bilateral external acoustic canal exostoses with smooth, convex, well-defined margins narrowing the external auditory canals.
Bilateral external auditory canal exostoses. High-resolution CT shows bilateral external acoustic canal exostoses with smooth, convex, well-defined margins narrowing the external auditory canals.

Q: On high-resolution CT imaging, bilateral, broad-based, convex thickenings of cortical bone narrowing the external auditory canal are highly characteristic of [...].
Bilateral external auditory canal exostoses. High-resolution CT shows bilateral external acoustic canal exostoses with smooth, convex, well-defined margins narrowing the external auditory canals.
Bilateral external auditory canal exostoses. High-resolution CT shows bilateral external acoustic canal exostoses with smooth, convex, well-defined margins narrowing the external auditory canals.
A: Exostosis (osteoma) of the ear
Back Extra: Exostosis (osteoma) of the ear
- Clinical: Patients with exostoses of the external auditory canal (EAC) and middle ear are generally asymptomatic, but can present with conductive hearing loss, otitis externa, otalgia, and cerumen impaction.
- Micro: Histologically, exostoses are composed of lamellar bone with anastomosing trabeculae and absent marrow spaces.
- Ancillary: High-resolution CT is the best modality for assessing exostoses, showing bilateral, broad-based, convex thickenings of cortical bone.
Reference Gallery:
Exostosis. This ear exostosis demonstrates thick trabeculae of bone beneath an intact squamous epithelium.
Exostosis. The bone is dense and thick, identified beneath an intact squamous epithelium. If on a pedicle, osteoma may be used as the diagnosis.
Exostosis. This high-power image demonstrates lamellar bone with thick, anastomosing trabeculae with reversal lines.
Ear osteoma. Axial CT showing an osteoma in the lateral aspect of the left external auditory canal, with a soft tissue plug lying medial in the meatus.
Bilateral external auditory canal exostoses. High-resolution CT shows bilateral external acoustic canal exostoses with smooth, convex, well-defined margins narrowing the external auditory canals.
Bilateral external auditory canal exostoses. High-resolution CT shows bilateral external acoustic canal exostoses with smooth, convex, well-defined margins narrowing the external auditory canals.

Q: Chronic otorrhea, otalgia, bleeding, hearing loss, and an enhancing soft tissue mass filling the ear canal are characteristic clinical and radiologic features of [...].
Squamous cell carcinoma of the external auditory canal. Posterior aspect of a pinnectomy with external auditory canal, tympanic membrane, and the malleus. A firm, grey to white tumour is seen involving the ear canal with extension into the soft tissues.
Squamous cell carcinoma of the external auditory canal. Axial (<<39216>>) and coronal (<<39217>>) postcontrast CT images (soft tissue windows) show enhancing soft tissue filling the left external auditory canal and middle ear in this biopsy-proven squamous cell carcinoma.
A: squamous cell carcinoma of the external auditory canal
Q: Squamous Cell Carcinoma of the External Auditory Canal
- Clinical: Chronic otorrhoea, otalgia, bleeding, hearing loss, and facial palsy are common nonspecific symptoms of [...].
- Micro: Most [...] are well-differentiated and keratinizing, with invasive nests of squamous cells and intercellular bridges.
- Ancillary: Immunohistochemistry for pancytokeratins, p40, p63, and CK5/6 is useful in confirming [...].
Reference Gallery:
Squamous cell carcinoma of the external auditory canal. Posterior aspect of a pinnectomy with external auditory canal, tympanic membrane, and the malleus. A firm, grey to white tumour is seen involving the ear canal with extension into the soft tissues.
Squamous cell carcinoma involving the external auditory canal. Section showing bony ear canal involved by squamous cell carcinoma and squamous cell carcinoma in situ.
Moderately differentiated squamous cell carcinoma. Section showing invasive nests of squamous cells with intercellular bridges, intracytoplasmic keratinization, and moderately enlarged nuclei with nucleoli.
Squamous cell carcinoma of the external auditory canal. Axial (<<39216>>) and coronal (<<39217>>) postcontrast CT images (soft tissue windows) show enhancing soft tissue filling the left external auditory canal and middle ear in this biopsy-proven squamous cell carcinoma.
Squamous cell carcinoma of the external auditory canal. Axial (<<39216>>) and coronal (<<39217>>) postcontrast CT images (soft tissue windows) show enhancing soft tissue filling the left external auditory canal and middle ear in this biopsy-proven squamous cell carcinoma.
Squamous cell carcinoma of the external auditory canal. Axial MRI (T1-weighted image shown here) showing enhancing soft tissue filling the left external auditory canal and middle ear, extending into the temporomandibular joint, with restricted diffusion on diffusion-weighted imaging.
Squamous cell carcinoma of the external auditory canal. Axial MRI (T1-weighted postcontrast fat-suppressed image shown here) showing enhancing soft tissue filling the left external auditory canal and middle ear, extending into the temporomandibular joint, with restricted diffusion on diffusion-weighted imaging.
Squamous cell carcinoma of the external auditory canal. Axial MRI (diffusion-weighted imaging at b1000 shown here) showing enhancing soft tissue filling the left external auditory canal and middle ear, extending into the temporomandibular joint, with restricted diffusion on diffusion-weighted imaging.
Squamous cell carcinoma of the external auditory canal. Axial MRI (apparent diffusion coefficient map image shown here) showing enhancing soft tissue filling the left external auditory canal and middle ear, extending into the temporomandibular joint, with restricted diffusion on diffusion-weighted imaging.
Squamous cell carcinoma of the external auditory canal. T1-weighted postcontrast fat-suppressed axial MRI shows a metastatic left level II lymph node.
A: Squamous Cell Carcinoma of the External Auditory Canal; Squamous Cell Carcinomas of the External Auditory Canal; Squamous Cell Carcinoma of the External Auditory Canal

Q: On microscopic examination, most cases of squamous cell carcinoma of the external auditory canal are characterized by invasive nests of squamous cells demonstrating intracytoplasmic keratinization and prominent [...].
Squamous cell carcinoma involving the external auditory canal. Section showing bony ear canal involved by squamous cell carcinoma and squamous cell carcinoma in situ.
Moderately differentiated squamous cell carcinoma. Section showing invasive nests of squamous cells with intercellular bridges, intracytoplasmic keratinization, and moderately enlarged nuclei with nucleoli.
A: intercellular bridges
Q: Squamous Cell Carcinoma of the External Auditory Canal
- Clinical: Chronic otorrhoea, otalgia, bleeding, hearing loss, and facial palsy are common nonspecific symptoms of [...].
- Micro: Most [...] are well-differentiated and keratinizing, with invasive nests of squamous cells and intercellular bridges.
- Ancillary: Immunohistochemistry for pancytokeratins, p40, p63, and CK5/6 is useful in confirming [...].
Reference Gallery:
Squamous cell carcinoma of the external auditory canal. Posterior aspect of a pinnectomy with external auditory canal, tympanic membrane, and the malleus. A firm, grey to white tumour is seen involving the ear canal with extension into the soft tissues.
Squamous cell carcinoma involving the external auditory canal. Section showing bony ear canal involved by squamous cell carcinoma and squamous cell carcinoma in situ.
Moderately differentiated squamous cell carcinoma. Section showing invasive nests of squamous cells with intercellular bridges, intracytoplasmic keratinization, and moderately enlarged nuclei with nucleoli.
Squamous cell carcinoma of the external auditory canal. Axial (<<39216>>) and coronal (<<39217>>) postcontrast CT images (soft tissue windows) show enhancing soft tissue filling the left external auditory canal and middle ear in this biopsy-proven squamous cell carcinoma.
Squamous cell carcinoma of the external auditory canal. Axial (<<39216>>) and coronal (<<39217>>) postcontrast CT images (soft tissue windows) show enhancing soft tissue filling the left external auditory canal and middle ear in this biopsy-proven squamous cell carcinoma.
Squamous cell carcinoma of the external auditory canal. Axial MRI (T1-weighted image shown here) showing enhancing soft tissue filling the left external auditory canal and middle ear, extending into the temporomandibular joint, with restricted diffusion on diffusion-weighted imaging.
Squamous cell carcinoma of the external auditory canal. Axial MRI (T1-weighted postcontrast fat-suppressed image shown here) showing enhancing soft tissue filling the left external auditory canal and middle ear, extending into the temporomandibular joint, with restricted diffusion on diffusion-weighted imaging.
Squamous cell carcinoma of the external auditory canal. Axial MRI (diffusion-weighted imaging at b1000 shown here) showing enhancing soft tissue filling the left external auditory canal and middle ear, extending into the temporomandibular joint, with restricted diffusion on diffusion-weighted imaging.
Squamous cell carcinoma of the external auditory canal. Axial MRI (apparent diffusion coefficient map image shown here) showing enhancing soft tissue filling the left external auditory canal and middle ear, extending into the temporomandibular joint, with restricted diffusion on diffusion-weighted imaging.
Squamous cell carcinoma of the external auditory canal. T1-weighted postcontrast fat-suppressed axial MRI shows a metastatic left level II lymph node.
A: Squamous Cell Carcinoma of the External Auditory Canal; Squamous Cell Carcinomas of the External Auditory Canal; Squamous Cell Carcinoma of the External Auditory Canal

Q: Otoscopic and intraoperative evaluation of a Cholesteatoma classically reveals an acquired middle ear mass predominantly composed of desquamated [...] debris.
Cholesteatoma. This otoscopic view demonstrates an acquired cholesteatoma, with keratin debris easily identified.
Cholesteatoma. This intraoperative image demonstrates the keratinous debris within a right attic cholesteatoma.
A: keratin
Q: Cholesteatoma
- Clinical: Patients with [...] often present with unrelenting or recurrent foul-smelling otorrhoea, tinnitus, and progressive hearing impairment.
- Micro: Histologically, [...] shows keratinizing stratified squamous epithelium, granulation tissue, and keratinaceous debris.
- Ancillary: Imaging studies such as CT and MRI are crucial in diagnosing [...], showing a non-enhancing soft tissue mass with bony erosion.
Reference Gallery:
Cholesteatoma. Axial CT of the petrous bones demonstrates a left mastoid cholesteatoma with scalloped bony erosion. Note the right-sided open cavity mastoidectomy for a previous contralateral cholesteatoma.
Cholesteatoma. A coronal diffusion-weighted imaging MRI sequence reveals left mastoid high signal consistent with cholesteatoma.
Cholesteatoma. There are layers of laminated, desquamated, and anucleated keratin filling the cystic luminal area, with only isolated intact squamous epithelial islands.
Cholesteatoma. A squamous epithelium with a prominent granular cell layer is noted within a cystic cavity filled with keratinous debris.
Cholesteatoma. This otoscopic view demonstrates an acquired cholesteatoma, with keratin debris easily identified.
Cholesteatoma. This intraoperative image demonstrates the keratinous debris within a right attic cholesteatoma.
A: cholesteatoma; cholesteatoma; cholesteatoma

Q: Histologically, a Cholesteatoma consists of a cystic space lined by keratinizing stratified squamous epithelium and filled with laminated, anucleated [...].
Cholesteatoma. There are layers of laminated, desquamated, and anucleated keratin filling the cystic luminal area, with only isolated intact squamous epithelial islands.
Cholesteatoma. A squamous epithelium with a prominent granular cell layer is noted within a cystic cavity filled with keratinous debris.
A: keratinaceous debris
Q: Cholesteatoma
- Clinical: Patients with [...] often present with unrelenting or recurrent foul-smelling otorrhoea, tinnitus, and progressive hearing impairment.
- Micro: Histologically, [...] shows keratinizing stratified squamous epithelium, granulation tissue, and keratinaceous debris.
- Ancillary: Imaging studies such as CT and MRI are crucial in diagnosing [...], showing a non-enhancing soft tissue mass with bony erosion.
Reference Gallery:
Cholesteatoma. Axial CT of the petrous bones demonstrates a left mastoid cholesteatoma with scalloped bony erosion. Note the right-sided open cavity mastoidectomy for a previous contralateral cholesteatoma.
Cholesteatoma. A coronal diffusion-weighted imaging MRI sequence reveals left mastoid high signal consistent with cholesteatoma.
Cholesteatoma. There are layers of laminated, desquamated, and anucleated keratin filling the cystic luminal area, with only isolated intact squamous epithelial islands.
Cholesteatoma. A squamous epithelium with a prominent granular cell layer is noted within a cystic cavity filled with keratinous debris.
Cholesteatoma. This otoscopic view demonstrates an acquired cholesteatoma, with keratin debris easily identified.
Cholesteatoma. This intraoperative image demonstrates the keratinous debris within a right attic cholesteatoma.
A: cholesteatoma; cholesteatoma; cholesteatoma

Q: Radiologically, a Cholesteatoma typically presents as a non-enhancing soft tissue mass in the middle ear or mastoid associated with characteristic scalloped [...].
Cholesteatoma. Axial CT of the petrous bones demonstrates a left mastoid cholesteatoma with scalloped bony erosion. Note the right-sided open cavity mastoidectomy for a previous contralateral cholesteatoma.
Cholesteatoma. A coronal diffusion-weighted imaging MRI sequence reveals left mastoid high signal consistent with cholesteatoma.
A: bony erosion
Q: Cholesteatoma
- Clinical: Patients with [...] often present with unrelenting or recurrent foul-smelling otorrhoea, tinnitus, and progressive hearing impairment.
- Micro: Histologically, [...] shows keratinizing stratified squamous epithelium, granulation tissue, and keratinaceous debris.
- Ancillary: Imaging studies such as CT and MRI are crucial in diagnosing [...], showing a non-enhancing soft tissue mass with bony erosion.
Reference Gallery:
Cholesteatoma. Axial CT of the petrous bones demonstrates a left mastoid cholesteatoma with scalloped bony erosion. Note the right-sided open cavity mastoidectomy for a previous contralateral cholesteatoma.
Cholesteatoma. A coronal diffusion-weighted imaging MRI sequence reveals left mastoid high signal consistent with cholesteatoma.
Cholesteatoma. There are layers of laminated, desquamated, and anucleated keratin filling the cystic luminal area, with only isolated intact squamous epithelial islands.
Cholesteatoma. A squamous epithelium with a prominent granular cell layer is noted within a cystic cavity filled with keratinous debris.
Cholesteatoma. This otoscopic view demonstrates an acquired cholesteatoma, with keratin debris easily identified.
Cholesteatoma. This intraoperative image demonstrates the keratinous debris within a right attic cholesteatoma.
A: cholesteatoma; cholesteatoma; cholesteatoma

Q: Histologically, an endolymphatic sac tumor is characterized by a single layer of cuboidal to columnar cells arranged in broad, interdigitating [...] projections, often accompanied by cystic spaces containing a colloid-like secretion.
Ear endolymphatic sac tumour. Bone fragments are usually identified in an endolymphatic sac tumour. There is a colloid-like secretion in the cystic spaces.
Ear endolymphatic sac tumour. The neoplastic cells are low cuboidal to slightly columnar, showing limited to absent pleomorphism. There is often a secretory material, histologically similar to thyroid gland colloid.
Endolymphatic sac tumour. Broad, interdigitating papillary projections composed of a single layer of cuboidal cells.
A: papillary
Back Extra: Endolymphatic Sac Tumour
- Clinical: Ipsilateral progressive hearing loss, tinnitus, facial nerve palsy, and vertigo are common presenting findings in patients with Endolymphatic Sac Tumour.
- Micro: The tumour is characterized by a single layer of low cuboidal to columnar epithelial cells arranged in simple, coarse, broad, interdigitating papillary projections with fibrovascular cores in Endolymphatic Sac Tumour.
- Ancillary: Neoplastic cells in Endolymphatic Sac Tumour are positive for pancytokeratin, CK7, HIF1α, EMA, GLUT1, CAIX (membranous), and PAX8 (nuclear).
Reference Gallery:
Ear endolymphatic sac tumour. A complex papillary proliferation is seen within an endolymphatic sac tumour.
Ear endolymphatic sac tumour. Bone fragments are usually identified in an endolymphatic sac tumour. There is a colloid-like secretion in the cystic spaces.
Ear endolymphatic sac tumour. The neoplastic cells are low cuboidal to slightly columnar, showing limited to absent pleomorphism. There is often a secretory material, histologically similar to thyroid gland colloid.
Ear endolymphatic sac tumour. The neoplastic cells show a low cuboidal to columnar cell appearance, lining papillary projections and dilated cystic spaces. Secretory material is frequently noted.
Ear endolymphatic sac tumour. The neoplastic cells show a strong and diffuse membranous reactivity for CAIX.
Ear endolymphatic sac tumour. The neoplastic cells show a strong and diffuse nuclear reactivity for PAX8.
Ear endolymphatic sac tumour. There is a large destructive mass affecting the temporal bone with extension into the cerebellum.
Ear endolymphatic sac tumour. This T1-weighted postcontrast MRI demonstrates the tumour as it destroys the bone and expands into the skull base, displacing the cerebellum.
Endolymphatic sac tumour. Broad, interdigitating papillary projections composed of a single layer of cuboidal cells.
Endolymphatic sac tumour. The neoplastic cells show a low cuboidal to columnar cell appearance with round nuclei lining dilated cystic spaces.

Q: Immunohistochemical analysis of an endolymphatic sac tumor characteristically demonstrates diffuse nuclear positivity for PAX8 and strong membranous reactivity for [...].
Ear endolymphatic sac tumour. The neoplastic cells show a strong and diffuse membranous reactivity for CAIX.
Ear endolymphatic sac tumour. The neoplastic cells show a strong and diffuse nuclear reactivity for PAX8.
A: CAIX
Back Extra: Endolymphatic Sac Tumour
- Clinical: Ipsilateral progressive hearing loss, tinnitus, facial nerve palsy, and vertigo are common presenting findings in patients with Endolymphatic Sac Tumour.
- Micro: The tumour is characterized by a single layer of low cuboidal to columnar epithelial cells arranged in simple, coarse, broad, interdigitating papillary projections with fibrovascular cores in Endolymphatic Sac Tumour.
- Ancillary: Neoplastic cells in Endolymphatic Sac Tumour are positive for pancytokeratin, CK7, HIF1α, EMA, GLUT1, CAIX (membranous), and PAX8 (nuclear).
Reference Gallery:
Ear endolymphatic sac tumour. A complex papillary proliferation is seen within an endolymphatic sac tumour.
Ear endolymphatic sac tumour. Bone fragments are usually identified in an endolymphatic sac tumour. There is a colloid-like secretion in the cystic spaces.
Ear endolymphatic sac tumour. The neoplastic cells are low cuboidal to slightly columnar, showing limited to absent pleomorphism. There is often a secretory material, histologically similar to thyroid gland colloid.
Ear endolymphatic sac tumour. The neoplastic cells show a low cuboidal to columnar cell appearance, lining papillary projections and dilated cystic spaces. Secretory material is frequently noted.
Ear endolymphatic sac tumour. The neoplastic cells show a strong and diffuse membranous reactivity for CAIX.
Ear endolymphatic sac tumour. The neoplastic cells show a strong and diffuse nuclear reactivity for PAX8.
Ear endolymphatic sac tumour. There is a large destructive mass affecting the temporal bone with extension into the cerebellum.
Ear endolymphatic sac tumour. This T1-weighted postcontrast MRI demonstrates the tumour as it destroys the bone and expands into the skull base, displacing the cerebellum.
Endolymphatic sac tumour. Broad, interdigitating papillary projections composed of a single layer of cuboidal cells.
Endolymphatic sac tumour. The neoplastic cells show a low cuboidal to columnar cell appearance with round nuclei lining dilated cystic spaces.

Q: On imaging and gross examination, an endolymphatic sac tumor typically presents as a destructive mass primarily affecting the [...], frequently extending into the cerebellopontine angle and displacing the cerebellum.
Ear endolymphatic sac tumour. There is a large destructive mass affecting the temporal bone with extension into the cerebellum.
Ear endolymphatic sac tumour. This T1-weighted postcontrast MRI demonstrates the tumour as it destroys the bone and expands into the skull base, displacing the cerebellum.
A: temporal bone
Back Extra: Endolymphatic Sac Tumour
- Clinical: Ipsilateral progressive hearing loss, tinnitus, facial nerve palsy, and vertigo are common presenting findings in patients with Endolymphatic Sac Tumour.
- Micro: The tumour is characterized by a single layer of low cuboidal to columnar epithelial cells arranged in simple, coarse, broad, interdigitating papillary projections with fibrovascular cores in Endolymphatic Sac Tumour.
- Ancillary: Neoplastic cells in Endolymphatic Sac Tumour are positive for pancytokeratin, CK7, HIF1α, EMA, GLUT1, CAIX (membranous), and PAX8 (nuclear).
Reference Gallery:
Ear endolymphatic sac tumour. A complex papillary proliferation is seen within an endolymphatic sac tumour.
Ear endolymphatic sac tumour. Bone fragments are usually identified in an endolymphatic sac tumour. There is a colloid-like secretion in the cystic spaces.
Ear endolymphatic sac tumour. The neoplastic cells are low cuboidal to slightly columnar, showing limited to absent pleomorphism. There is often a secretory material, histologically similar to thyroid gland colloid.
Ear endolymphatic sac tumour. The neoplastic cells show a low cuboidal to columnar cell appearance, lining papillary projections and dilated cystic spaces. Secretory material is frequently noted.
Ear endolymphatic sac tumour. The neoplastic cells show a strong and diffuse membranous reactivity for CAIX.
Ear endolymphatic sac tumour. The neoplastic cells show a strong and diffuse nuclear reactivity for PAX8.
Ear endolymphatic sac tumour. There is a large destructive mass affecting the temporal bone with extension into the cerebellum.
Ear endolymphatic sac tumour. This T1-weighted postcontrast MRI demonstrates the tumour as it destroys the bone and expands into the skull base, displacing the cerebellum.
Endolymphatic sac tumour. Broad, interdigitating papillary projections composed of a single layer of cuboidal cells.
Endolymphatic sac tumour. The neoplastic cells show a low cuboidal to columnar cell appearance with round nuclei lining dilated cystic spaces.

Q: Histologically, Middle Ear Adenocarcinoma is characterized by a complex [...] glandular pattern lined by mucin-producing epithelial cells.
Middle ear adenocarcinoma. There is a very complex papillary architecture, with mucinous producing cells. A concurrent cholesteatoma is noted (upper left).
A: cystic-papillary
Back Extra: Middle Ear Adenocarcinoma
- Clinical: Symptoms of Middle Ear Adenocarcinoma are often nonspecific and include hearing loss, otalgia, vestibular dysfunction, and otorrhoea.
- Micro: Middle Ear Adenocarcinoma shows a cystic-papillary glandular pattern with a complex architecture, including papillae lined by low cuboidal to columnar epithelial cells with abundant mucinous material.
- Ancillary: Tumour cells in Middle Ear Adenocarcinoma are positive for CK7, EMA, and (sometimes) S100, but negative for PAX8 and CAIX, which helps in distinguishing it from endolymphatic sac tumour.
Reference Gallery:
Middle ear adenocarcinoma. There is a very complex papillary architecture, with mucinous producing cells. A concurrent cholesteatoma is noted (upper left).
Middle ear adenocarcinoma. Cuboidal to columnar epithelial cells are noted lining the papillae. There is easily identified mucin production.
Middle ear adenocarcinoma. The columnar cells show basally located nuclei and abundant mucinous material in the cytoplasm. Pleomorphism is limited.

Q: At the cellular level, the papillae in Middle Ear Adenocarcinoma are lined by low cuboidal to columnar cells that characteristically contain abundant intracellular [...] material.
Middle ear adenocarcinoma. Cuboidal to columnar epithelial cells are noted lining the papillae. There is easily identified mucin production.
Middle ear adenocarcinoma. The columnar cells show basally located nuclei and abundant mucinous material in the cytoplasm. Pleomorphism is limited.
A: mucinous
Back Extra: Middle Ear Adenocarcinoma
- Clinical: Symptoms of Middle Ear Adenocarcinoma are often nonspecific and include hearing loss, otalgia, vestibular dysfunction, and otorrhoea.
- Micro: Middle Ear Adenocarcinoma shows a cystic-papillary glandular pattern with a complex architecture, including papillae lined by low cuboidal to columnar epithelial cells with abundant mucinous material.
- Ancillary: Tumour cells in Middle Ear Adenocarcinoma are positive for CK7, EMA, and (sometimes) S100, but negative for PAX8 and CAIX, which helps in distinguishing it from endolymphatic sac tumour.
Reference Gallery:
Middle ear adenocarcinoma. There is a very complex papillary architecture, with mucinous producing cells. A concurrent cholesteatoma is noted (upper left).
Middle ear adenocarcinoma. Cuboidal to columnar epithelial cells are noted lining the papillae. There is easily identified mucin production.
Middle ear adenocarcinoma. The columnar cells show basally located nuclei and abundant mucinous material in the cytoplasm. Pleomorphism is limited.

Q: A characteristic histologic finding in a middle ear neuroendocrine tumor is the presence of uniform cells with distinct borders and round nuclei that exhibit a delicate [...] chromatin distribution.
Middle ear neuroendocrine tumour. Surface epithelium (upper right) is separated from the neoplastic cells that show ample cytoplasm surrounding round nuclei with delicate salt-and-pepper chromatin distribution.
Middle ear neuroendocrine tumour. The tumour cells are well differentiated and have characteristic neuroendocrine morphology.
A: salt-and-pepper
Back Extra: Middle Ear Neuroendocrine Tumour
- Clinical: Symptoms include hearing changes, fullness or ear pressure, and tinnitus. Otoscopy reveals a grey-white or fibrotic mass behind an intact tympanic membrane.
- Micro: Tumours exhibit cuboidal to columnar cells with distinct cell borders and eosinophilic cytoplasm, showing various growth patterns including glandular, trabecular, and sheet-like configurations.
- Ancillary: Neoplastic cells coexpress keratins and neuroendocrine markers (synaptophysin, chromogranin) along with the transcription factors INSM1, ISL1, and SATB2.
Reference Gallery:
Middle ear neuroendocrine tumour. The tumour cells are well differentiated and have characteristic neuroendocrine morphology.
Middle ear neuroendocrine tumour. This L-cell tumour has characteristic trabecular and whorled architecture with focal solid nests.
Middle ear neuroendocrine tumour. The tumour cells are well differentiated and have characteristic neuroendocrine morphology.
Middle ear neuroendocrine tumour. The tumour cells express the transcription factor SATB2.
Middle ear neuroendocrine tumour. These tumours most often show L-cell differentiation characterized by whorled trabecular architecture and expression of PP (shown) as well as glucagon.
Middle ear neuroendocrine tumour. These tumours most often show L-cell differentiation, characterized by a whorled trabecular architecture and expression of glucagon.
Middle ear neuroendocrine tumour. These tumours are well-differentiated neuroendocrine tumours that express SSTR2.
Middle ear neuroendocrine tumour. The tumour cells of these middle ear neoplasms express INSM1 uniformly, even in areas that were formerly thought to be epithelial non-neuroendocrine components.
Middle ear neuroendocrine tumour. Surface epithelium (upper right) is separated from the neoplastic cells that show ample cytoplasm surrounding round nuclei with delicate salt-and-pepper chromatin distribution.
Middle ear mixed epithelial neuroendocrine tumour. The neoplastic proliferation has expanded below the middle ear epithelium. There are various growth patterns with cords and small glands.
Middle ear mixed epithelial neuroendocrine tumour. Various growth patterns with cords and small glands.

Q: In addition to classic neuroendocrine markers (synaptophysin, chromogranin), the neoplastic cells of a middle ear neuroendocrine tumor characteristically express the transcription factors INSM1, ISL1, and [...].
Middle ear neuroendocrine tumour. The tumour cells express the transcription factor SATB2.
Middle ear neuroendocrine tumour. The tumour cells of these middle ear neoplasms express INSM1 uniformly, even in areas that were formerly thought to be epithelial non-neuroendocrine components.
A: SATB2
Back Extra: Middle Ear Neuroendocrine Tumour
- Clinical: Symptoms include hearing changes, fullness or ear pressure, and tinnitus. Otoscopy reveals a grey-white or fibrotic mass behind an intact tympanic membrane.
- Micro: Tumours exhibit cuboidal to columnar cells with distinct cell borders and eosinophilic cytoplasm, showing various growth patterns including glandular, trabecular, and sheet-like configurations.
- Ancillary: Neoplastic cells coexpress keratins and neuroendocrine markers (synaptophysin, chromogranin) along with the transcription factors INSM1, ISL1, and SATB2.
Reference Gallery:
Middle ear neuroendocrine tumour. The tumour cells are well differentiated and have characteristic neuroendocrine morphology.
Middle ear neuroendocrine tumour. This L-cell tumour has characteristic trabecular and whorled architecture with focal solid nests.
Middle ear neuroendocrine tumour. The tumour cells are well differentiated and have characteristic neuroendocrine morphology.
Middle ear neuroendocrine tumour. The tumour cells express the transcription factor SATB2.
Middle ear neuroendocrine tumour. These tumours most often show L-cell differentiation characterized by whorled trabecular architecture and expression of PP (shown) as well as glucagon.
Middle ear neuroendocrine tumour. These tumours most often show L-cell differentiation, characterized by a whorled trabecular architecture and expression of glucagon.
Middle ear neuroendocrine tumour. These tumours are well-differentiated neuroendocrine tumours that express SSTR2.
Middle ear neuroendocrine tumour. The tumour cells of these middle ear neoplasms express INSM1 uniformly, even in areas that were formerly thought to be epithelial non-neuroendocrine components.
Middle ear neuroendocrine tumour. Surface epithelium (upper right) is separated from the neoplastic cells that show ample cytoplasm surrounding round nuclei with delicate salt-and-pepper chromatin distribution.
Middle ear mixed epithelial neuroendocrine tumour. The neoplastic proliferation has expanded below the middle ear epithelium. There are various growth patterns with cords and small glands.
Middle ear mixed epithelial neuroendocrine tumour. Various growth patterns with cords and small glands.

Q: A distinctive subset of middle ear neuroendocrine tumors demonstrates [...] differentiation, which is characterized by a whorled trabecular architecture and positive staining for glucagon and pancreatic polypeptide (PP).
Middle ear neuroendocrine tumour. This L-cell tumour has characteristic trabecular and whorled architecture with focal solid nests.
Middle ear neuroendocrine tumour. These tumours most often show L-cell differentiation, characterized by a whorled trabecular architecture and expression of glucagon.
A: L-cell
Back Extra: Middle Ear Neuroendocrine Tumour
- Clinical: Symptoms include hearing changes, fullness or ear pressure, and tinnitus. Otoscopy reveals a grey-white or fibrotic mass behind an intact tympanic membrane.
- Micro: Tumours exhibit cuboidal to columnar cells with distinct cell borders and eosinophilic cytoplasm, showing various growth patterns including glandular, trabecular, and sheet-like configurations.
- Ancillary: Neoplastic cells coexpress keratins and neuroendocrine markers (synaptophysin, chromogranin) along with the transcription factors INSM1, ISL1, and SATB2.
Reference Gallery:
Middle ear neuroendocrine tumour. The tumour cells are well differentiated and have characteristic neuroendocrine morphology.
Middle ear neuroendocrine tumour. This L-cell tumour has characteristic trabecular and whorled architecture with focal solid nests.
Middle ear neuroendocrine tumour. The tumour cells are well differentiated and have characteristic neuroendocrine morphology.
Middle ear neuroendocrine tumour. The tumour cells express the transcription factor SATB2.
Middle ear neuroendocrine tumour. These tumours most often show L-cell differentiation characterized by whorled trabecular architecture and expression of PP (shown) as well as glucagon.
Middle ear neuroendocrine tumour. These tumours most often show L-cell differentiation, characterized by a whorled trabecular architecture and expression of glucagon.
Middle ear neuroendocrine tumour. These tumours are well-differentiated neuroendocrine tumours that express SSTR2.
Middle ear neuroendocrine tumour. The tumour cells of these middle ear neoplasms express INSM1 uniformly, even in areas that were formerly thought to be epithelial non-neuroendocrine components.
Middle ear neuroendocrine tumour. Surface epithelium (upper right) is separated from the neoplastic cells that show ample cytoplasm surrounding round nuclei with delicate salt-and-pepper chromatin distribution.
Middle ear mixed epithelial neuroendocrine tumour. The neoplastic proliferation has expanded below the middle ear epithelium. There are various growth patterns with cords and small glands.
Middle ear mixed epithelial neuroendocrine tumour. Various growth patterns with cords and small glands.

Q: The histologic hallmark of Middle Ear Papilloma is the inverted growth of multilayered [...] epithelium without pleomorphism or tumor necrosis.
Middle ear papilloma. A multilayered transitional epithelium shows an inverted growth into the stroma of the middle ear. There is no pleomorphism or tumour necrosis.
Middle ear papilloma. Transepithelial inflammatory cells are seen in this multilayered epithelium. There is an overall inverted growth to the tumour.
A: transitional
Back Extra: Middle Ear Papilloma
- Clinical: Patients with middle ear papilloma often present with hearing loss, otorrhoea, and a mass; concurrent Eustachian tube involvement is common.
- Micro: The hallmark of middle ear papilloma is the inverted growth of multilayered transitional epithelium with no pleomorphism or tumour necrosis.
- Ancillary: Low-risk HPV has been identified in a few cases of middle ear papilloma, but neither EGFR nor KRAS mutations have been documented.
Reference Gallery:
Middle ear papilloma. This coronal T1-weighted postcontrast fat-suppressed image demonstrates destructive growth into the mastoid bone.
Middle ear papilloma. This axial T2-weighted fat-suppressed image demonstrates masses in both the sinonasal tract and the temporal bone, with carcinoma identified in both locations.
Middle ear papilloma. Spicules of bone are being remodelled by the inverted neoplastic islands of transitional epithelium in this middle ear papilloma.
Middle ear papilloma. A multilayered transitional epithelium shows an inverted growth into the stroma of the middle ear. There is no pleomorphism or tumour necrosis.
Middle ear papilloma. Transepithelial inflammatory cells are seen in this multilayered epithelium. There is an overall inverted growth to the tumour.

Q: Despite a lack of overt cytologic atypia, Middle Ear Papilloma can exhibit locally destructive behavior due to its [...] growth pattern, which frequently causes remodeling of adjacent bone.
Middle ear papilloma. This coronal T1-weighted postcontrast fat-suppressed image demonstrates destructive growth into the mastoid bone.
Middle ear papilloma. Spicules of bone are being remodelled by the inverted neoplastic islands of transitional epithelium in this middle ear papilloma.
A: inverted
Back Extra: Middle Ear Papilloma
- Clinical: Patients with middle ear papilloma often present with hearing loss, otorrhoea, and a mass; concurrent Eustachian tube involvement is common.
- Micro: The hallmark of middle ear papilloma is the inverted growth of multilayered transitional epithelium with no pleomorphism or tumour necrosis.
- Ancillary: Low-risk HPV has been identified in a few cases of middle ear papilloma, but neither EGFR nor KRAS mutations have been documented.
Reference Gallery:
Middle ear papilloma. This coronal T1-weighted postcontrast fat-suppressed image demonstrates destructive growth into the mastoid bone.
Middle ear papilloma. This axial T2-weighted fat-suppressed image demonstrates masses in both the sinonasal tract and the temporal bone, with carcinoma identified in both locations.
Middle ear papilloma. Spicules of bone are being remodelled by the inverted neoplastic islands of transitional epithelium in this middle ear papilloma.
Middle ear papilloma. A multilayered transitional epithelium shows an inverted growth into the stroma of the middle ear. There is no pleomorphism or tumour necrosis.
Middle ear papilloma. Transepithelial inflammatory cells are seen in this multilayered epithelium. There is an overall inverted growth to the tumour.

Q: Histologically, Middle Ear Squamous Cell Carcinoma typically features infiltrating nests of pleomorphic cells with a pavemented appearance, frequently demonstrating a desmoplastic stromal reaction, bone invasion, and abundant [...].
Middle ear squamous cell carcinoma. A fragment of bone is noted, along with a desmoplastic stromal reaction to an invasive squamous cell carcinoma, showing abundant keratinization and easily identified pleomorphism.
A: keratinization
Back Extra: Middle Ear Squamous Cell Carcinoma
- Clinical: Middle ear squamous cell carcinoma (MeSCC) typically presents with symptoms such as hearing loss, otorrhoea, otalgia, and facial nerve palsy.
- Micro: Histologically, MeSCC shows pleomorphic epithelial cells arranged in sheets with a pavemented appearance, increased N:C ratio, and coarse nuclear chromatin. Most tumours are keratinizing and well to moderately differentiated.
- Ancillary: Immunohistochemistry for pancytokeratin, p40, p63, and CK5/6 is positive in MeSCC.
Reference Gallery:
Middle ear squamous cell carcinoma. A tumour arising within a background of cholesteatoma. There is destruction of the malleus by infiltrating nests of squamous cells with moderate cytological atypia.
Middle ear squamous cell carcinoma. A fragment of bone is noted, along with a desmoplastic stromal reaction to an invasive squamous cell carcinoma, showing abundant keratinization and easily identified pleomorphism.

Q: Middle Ear Squamous Cell Carcinoma may arise within the background of a preexisting [...], presenting as an infiltrative tumor that can destroy middle ear ossicles such as the malleus.
Middle ear squamous cell carcinoma. A tumour arising within a background of cholesteatoma. There is destruction of the malleus by infiltrating nests of squamous cells with moderate cytological atypia.
A: cholesteatoma
Back Extra: Middle Ear Squamous Cell Carcinoma
- Clinical: Middle ear squamous cell carcinoma (MeSCC) typically presents with symptoms such as hearing loss, otorrhoea, otalgia, and facial nerve palsy.
- Micro: Histologically, MeSCC shows pleomorphic epithelial cells arranged in sheets with a pavemented appearance, increased N:C ratio, and coarse nuclear chromatin. Most tumours are keratinizing and well to moderately differentiated.
- Ancillary: Immunohistochemistry for pancytokeratin, p40, p63, and CK5/6 is positive in MeSCC.
Reference Gallery:
Middle ear squamous cell carcinoma. A tumour arising within a background of cholesteatoma. There is destruction of the malleus by infiltrating nests of squamous cells with moderate cytological atypia.
Middle ear squamous cell carcinoma. A fragment of bone is noted, along with a desmoplastic stromal reaction to an invasive squamous cell carcinoma, showing abundant keratinization and easily identified pleomorphism.

Q: The radiolucent, active phase of Otosclerosis—characterized by zones of active bone resorption and spongy immature bone—is specifically referred to as [...].
Otosclerosis. Axial CT of the petrous bones demonstrates a bilateral pericochlear lucency consistent with retrofenestral otospongiosis.
A: otospongiosis
Back Extra: Otosclerosis
- Clinical: Otosclerosis is a common cause of conductive hearing loss, often bilateral with initial asymmetrical hearing loss. It may also present with sensorineural hearing loss, tinnitus, and vertigo.
- Micro: Histologically, active areas (otospongiosis) show zones of active bone resorption with spongy immature bone, enlarged plump osteoblasts, osteoclastic giant cells, and dilated vascular marrow spaces.
- Ancillary: High-resolution CT is useful for identifying bilateral otic capsule demineralization and new bone formation in otosclerosis.
Reference Gallery:
Otosclerosis. Axial CT of the petrous bones demonstrates a bilateral pericochlear lucency consistent with retrofenestral otospongiosis.
Ear otosclerosis. Axial high-resolution CT shows bilateral otic capsule demineralization and new bone formation obstructing both oval windows.
Ear otosclerosis. Endoscopic image of the left ear, showing otosclerosis. Fn, facial nerve; m, malleus handle; O, otosclerotic focus; pe, pyramidal eminence; Rw, round window niche; TM, tympanic membrane.

Q: High-resolution CT imaging of Otosclerosis characteristically shows bilateral otic capsule demineralization and new bone formation that frequently obstructs the [...].
Ear otosclerosis. Axial high-resolution CT shows bilateral otic capsule demineralization and new bone formation obstructing both oval windows.
Ear otosclerosis. Endoscopic image of the left ear, showing otosclerosis. Fn, facial nerve; m, malleus handle; O, otosclerotic focus; pe, pyramidal eminence; Rw, round window niche; TM, tympanic membrane.
A: oval window
Back Extra: Otosclerosis
- Clinical: Otosclerosis is a common cause of conductive hearing loss, often bilateral with initial asymmetrical hearing loss. It may also present with sensorineural hearing loss, tinnitus, and vertigo.
- Micro: Histologically, active areas (otospongiosis) show zones of active bone resorption with spongy immature bone, enlarged plump osteoblasts, osteoclastic giant cells, and dilated vascular marrow spaces.
- Ancillary: High-resolution CT is useful for identifying bilateral otic capsule demineralization and new bone formation in otosclerosis.
Reference Gallery:
Otosclerosis. Axial CT of the petrous bones demonstrates a bilateral pericochlear lucency consistent with retrofenestral otospongiosis.
Ear otosclerosis. Axial high-resolution CT shows bilateral otic capsule demineralization and new bone formation obstructing both oval windows.
Ear otosclerosis. Endoscopic image of the left ear, showing otosclerosis. Fn, facial nerve; m, malleus handle; O, otosclerotic focus; pe, pyramidal eminence; Rw, round window niche; TM, tympanic membrane.

Q: Histologically, Vestibular Schwannoma features alternating hypercellular Antoni A areas with nuclear palisading (often forming [...]) and hypocellular, myxoid Antoni B areas.
Vestibular schwannoma. Alternating areas of hypercellularity and hypocellularity are seen in this schwannoma.
Vestibular schwannoma. The hypocellular (Antoni B) areas show a myxoid background material, adjacent to areas of slightly increased cellularity.
Vestibular schwannoma. Parallel nuclear palisading (Verocay body) is a feature seen in schwannoma. The nuclei are wavy or buckled.
A: Verocay bodies
Back Extra: Vestibular Schwannoma
- Clinical: The majority (> 90%) of patients with Vestibular Schwannoma present with ipsilateral sensorineural hearing loss, frequently unrecognized by the patients.
- Micro: Vestibular schwannomas show compact hypercellular Antoni A areas with occasional nuclear palisading, alternating with loosely arranged Antoni B foci.
- Ancillary: There is strong and diffuse nuclear and cytoplasmic reactivity for S100 and SOX10 by immunohistochemistry.
Reference Gallery:
Vestibular schwannoma. Alternating areas of hypercellularity and hypocellularity are seen in this schwannoma.
Vestibular schwannoma. Interlacing fascicles of spindled cells are seen in this schwannoma. The nuclei are pointed and elongated.
Vestibular schwannoma. The hypocellular (Antoni B) areas show a myxoid background material, adjacent to areas of slightly increased cellularity.
Vestibular schwannoma. Parallel nuclear palisading (Verocay body) is a feature seen in schwannoma. The nuclei are wavy or buckled.
Vestibular schwannoma. The nuclei in schwannoma range from slightly blunted to pointed and buckled, set within a fibrillar cytoplasm.
Vestibular schwannoma. It is not uncommon to have areas of hypocellularity with fibrosis, sometimes partly obscuring the nature of the neoplastic proliferation. However, fibrillar cytoplasm is seen associated with pointy nuclei.
Vestibular schwannoma. There is a strong and diffuse nuclear and cytoplasmic reactivity for S100 by immunohistochemistry.
Vestibular schwannoma. T2-weighted CISS axial image showing a large left-sided cerebellopontine angle cistern and internal auditory meatus mass with peritumoural cystic change and distortion of the posterior fossa structures.

Q: By immunohistochemistry, Vestibular Schwannoma demonstrates strong and diffuse nuclear and cytoplasmic reactivity for SOX10 and [...].
Vestibular schwannoma. There is a strong and diffuse nuclear and cytoplasmic reactivity for S100 by immunohistochemistry.
A: S100
Back Extra: Vestibular Schwannoma
- Clinical: The majority (> 90%) of patients with Vestibular Schwannoma present with ipsilateral sensorineural hearing loss, frequently unrecognized by the patients.
- Micro: Vestibular schwannomas show compact hypercellular Antoni A areas with occasional nuclear palisading, alternating with loosely arranged Antoni B foci.
- Ancillary: There is strong and diffuse nuclear and cytoplasmic reactivity for S100 and SOX10 by immunohistochemistry.
Reference Gallery:
Vestibular schwannoma. Alternating areas of hypercellularity and hypocellularity are seen in this schwannoma.
Vestibular schwannoma. Interlacing fascicles of spindled cells are seen in this schwannoma. The nuclei are pointed and elongated.
Vestibular schwannoma. The hypocellular (Antoni B) areas show a myxoid background material, adjacent to areas of slightly increased cellularity.
Vestibular schwannoma. Parallel nuclear palisading (Verocay body) is a feature seen in schwannoma. The nuclei are wavy or buckled.
Vestibular schwannoma. The nuclei in schwannoma range from slightly blunted to pointed and buckled, set within a fibrillar cytoplasm.
Vestibular schwannoma. It is not uncommon to have areas of hypocellularity with fibrosis, sometimes partly obscuring the nature of the neoplastic proliferation. However, fibrillar cytoplasm is seen associated with pointy nuclei.
Vestibular schwannoma. There is a strong and diffuse nuclear and cytoplasmic reactivity for S100 by immunohistochemistry.
Vestibular schwannoma. T2-weighted CISS axial image showing a large left-sided cerebellopontine angle cistern and internal auditory meatus mass with peritumoural cystic change and distortion of the posterior fossa structures.

Q: Clinically, >90% of patients with Vestibular Schwannoma present with ipsilateral [...] due to mass effect in the cerebellopontine angle.
Vestibular schwannoma. T2-weighted CISS axial image showing a large left-sided cerebellopontine angle cistern and internal auditory meatus mass with peritumoural cystic change and distortion of the posterior fossa structures.
A: sensorineural hearing loss
Back Extra: Vestibular Schwannoma
- Clinical: The majority (> 90%) of patients with Vestibular Schwannoma present with ipsilateral sensorineural hearing loss, frequently unrecognized by the patients.
- Micro: Vestibular schwannomas show compact hypercellular Antoni A areas with occasional nuclear palisading, alternating with loosely arranged Antoni B foci.
- Ancillary: There is strong and diffuse nuclear and cytoplasmic reactivity for S100 and SOX10 by immunohistochemistry.
Reference Gallery:
Vestibular schwannoma. Alternating areas of hypercellularity and hypocellularity are seen in this schwannoma.
Vestibular schwannoma. Interlacing fascicles of spindled cells are seen in this schwannoma. The nuclei are pointed and elongated.
Vestibular schwannoma. The hypocellular (Antoni B) areas show a myxoid background material, adjacent to areas of slightly increased cellularity.
Vestibular schwannoma. Parallel nuclear palisading (Verocay body) is a feature seen in schwannoma. The nuclei are wavy or buckled.
Vestibular schwannoma. The nuclei in schwannoma range from slightly blunted to pointed and buckled, set within a fibrillar cytoplasm.
Vestibular schwannoma. It is not uncommon to have areas of hypocellularity with fibrosis, sometimes partly obscuring the nature of the neoplastic proliferation. However, fibrillar cytoplasm is seen associated with pointy nuclei.
Vestibular schwannoma. There is a strong and diffuse nuclear and cytoplasmic reactivity for S100 by immunohistochemistry.
Vestibular schwannoma. T2-weighted CISS axial image showing a large left-sided cerebellopontine angle cistern and internal auditory meatus mass with peritumoural cystic change and distortion of the posterior fossa structures.

Q: Patients with Ataxia-Telangiectasia develop progressive cerebellar ataxia, telangiectases, immunodeficiency, and an increased risk of malignancies, particularly [...] (e.g., diffuse large B-cell lymphoma).
Large B-cell lymphoma. Retropharyngeal lymphadenopathy and Waldeyer ring fullness in a patient with ataxia–telangiectasia.
Large B-cell lymphoma. Strong CD20 expression in a diffuse large B-cell lymphoma involving the neck in a patient with ataxia–telangiectasia.
A: lymphoid neoplasms
Back Extra: Ataxia-Telangiectasia
- Clinical: Patients with ataxia-telangiectasia (AT) develop progressive cerebellar ataxia, telangiectases, immunosuppression, recurrent sinopulmonary infections, and increased risk of malignancies, particularly lymphoid neoplasms.
- Micro: Microscopically, the tumours in AT patients do not show significant differences compared to their sporadic counterparts.
- Ancillary: Essential diagnostic criteria for AT include characteristic neurological (ataxia, cerebellar degeneration) and non-neurological manifestations (telangiectases), elevated alpha-fetoprotein (AFP), decreased immunoglobulins, and increased chromosome breakage after X-ray exposure.
Reference Gallery:
Large B-cell lymphoma. Retropharyngeal lymphadenopathy and Waldeyer ring fullness in a patient with ataxia–telangiectasia.
Large B-cell lymphoma. Strong CD20 expression in a diffuse large B-cell lymphoma involving the neck in a patient with ataxia–telangiectasia.
Somatic ATM mutation in squamous cell carcinoma. Somatic mutations in ATM have been reported with increasing frequency in a variety of tumour types, including squamous cell carcinoma of the head and neck. In this example, next-generation sequencing detected several somatic gene variants involving ATM, including this ATM p.Q1416* nonsense variant, in a lymph node metastasis from a patient with a history of facial squamous cell carcinomas.

Q: While Ataxia-Telangiectasia is an inherited syndrome, somatic mutations involving the [...] gene are increasingly detected by next-generation sequencing in a variety of sporadic tumors, such as head and neck squamous cell carcinoma.
Somatic ATM mutation in squamous cell carcinoma. Somatic mutations in ATM have been reported with increasing frequency in a variety of tumour types, including squamous cell carcinoma of the head and neck. In this example, next-generation sequencing detected several somatic gene variants involving ATM, including this ATM p.Q1416* nonsense variant, in a lymph node metastasis from a patient with a history of facial squamous cell carcinomas.
A: ATM
Back Extra: Ataxia-Telangiectasia
- Clinical: Patients with ataxia-telangiectasia (AT) develop progressive cerebellar ataxia, telangiectases, immunosuppression, recurrent sinopulmonary infections, and increased risk of malignancies, particularly lymphoid neoplasms.
- Micro: Microscopically, the tumours in AT patients do not show significant differences compared to their sporadic counterparts.
- Ancillary: Essential diagnostic criteria for AT include characteristic neurological (ataxia, cerebellar degeneration) and non-neurological manifestations (telangiectases), elevated alpha-fetoprotein (AFP), decreased immunoglobulins, and increased chromosome breakage after X-ray exposure.
Reference Gallery:
Large B-cell lymphoma. Retropharyngeal lymphadenopathy and Waldeyer ring fullness in a patient with ataxia–telangiectasia.
Large B-cell lymphoma. Strong CD20 expression in a diffuse large B-cell lymphoma involving the neck in a patient with ataxia–telangiectasia.
Somatic ATM mutation in squamous cell carcinoma. Somatic mutations in ATM have been reported with increasing frequency in a variety of tumour types, including squamous cell carcinoma of the head and neck. In this example, next-generation sequencing detected several somatic gene variants involving ATM, including this ATM p.Q1416* nonsense variant, in a lymph node metastasis from a patient with a history of facial squamous cell carcinomas.

Q: Salivary gland involvement in Brooke-Spiegler Syndrome is typically characterized by multicentric basal cell adenomas exhibiting a characteristic [...]-type growth pattern.
Parotid tumour in Brooke–Spiegler syndrome. Salivary gland involvement is characterized by the presence of multicentric membranous-type basal cell adenoma. 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 cell nests are separated by dense hyaline stroma.
Basal cell adenoma. Membranous type. Salivary gland involvement in this syndrome is characterized by the presence of membranous-type basal cell adenoma, 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.
A: membranous
Back Extra: Brooke-Spiegler Syndrome
- Clinical: Multiple spiradenomas, cylindromas, and trichoepitheliomas, often coalescing into nodules that grow throughout life and increase in number with age.
- Micro: Multicentric basal cell adenomas with a membranous-type growth pattern, characterized by peripheral palisading of dark cells and a dense hyaline stroma.
- Ancillary: Presence of a constitutional heterozygous pathogenic variant in the CYLD gene confirms the diagnosis.
Reference Gallery:
Basal cell adenoma. Low-power view showing a well-circumscribed parotid basal cell adenoma, present in a patient with Brooke–Spiegler syndrome / familial cylindromatosis syndrome.
Parotid tumour in Brooke–Spiegler syndrome. Salivary gland involvement is characterized by the presence of multicentric membranous-type basal cell adenoma. 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 cell nests are separated by dense hyaline stroma.
Basal cell adenoma. Membranous type. Salivary gland involvement in this syndrome is characterized by the presence of membranous-type basal cell adenoma, 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.

Q: Brooke-Spiegler Syndrome (characterized by multiple cutaneous cylindromas, spiradenomas, and salivary basal cell adenomas) is confirmed by identifying a constitutional heterozygous pathogenic variant in the [...] gene.
Basal cell adenoma. Low-power view showing a well-circumscribed parotid basal cell adenoma, present in a patient with Brooke–Spiegler syndrome / familial cylindromatosis syndrome.
A: CYLD
Back Extra: Brooke-Spiegler Syndrome
- Clinical: Multiple spiradenomas, cylindromas, and trichoepitheliomas, often coalescing into nodules that grow throughout life and increase in number with age.
- Micro: Multicentric basal cell adenomas with a membranous-type growth pattern, characterized by peripheral palisading of dark cells and a dense hyaline stroma.
- Ancillary: Presence of a constitutional heterozygous pathogenic variant in the CYLD gene confirms the diagnosis.
Reference Gallery:
Basal cell adenoma. Low-power view showing a well-circumscribed parotid basal cell adenoma, present in a patient with Brooke–Spiegler syndrome / familial cylindromatosis syndrome.
Parotid tumour in Brooke–Spiegler syndrome. Salivary gland involvement is characterized by the presence of multicentric membranous-type basal cell adenoma. 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 cell nests are separated by dense hyaline stroma.
Basal cell adenoma. Membranous type. Salivary gland involvement in this syndrome is characterized by the presence of membranous-type basal cell adenoma, 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.

Q: Microscopically, the salivary tumors in Brooke-Spiegler Syndrome typically demonstrate nests of basaloid cells with peripheral palisading that are separated by a dense [...].
Parotid tumour in Brooke–Spiegler syndrome. Salivary gland involvement is characterized by the presence of multicentric membranous-type basal cell adenoma. 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 cell nests are separated by dense hyaline stroma.
Basal cell adenoma. Membranous type. Salivary gland involvement in this syndrome is characterized by the presence of membranous-type basal cell adenoma, 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.
A: hyaline stroma
Back Extra: Brooke-Spiegler Syndrome
- Clinical: Multiple spiradenomas, cylindromas, and trichoepitheliomas, often coalescing into nodules that grow throughout life and increase in number with age.
- Micro: Multicentric basal cell adenomas with a membranous-type growth pattern, characterized by peripheral palisading of dark cells and a dense hyaline stroma.
- Ancillary: Presence of a constitutional heterozygous pathogenic variant in the CYLD gene confirms the diagnosis.
Reference Gallery:
Basal cell adenoma. Low-power view showing a well-circumscribed parotid basal cell adenoma, present in a patient with Brooke–Spiegler syndrome / familial cylindromatosis syndrome.
Parotid tumour in Brooke–Spiegler syndrome. Salivary gland involvement is characterized by the presence of multicentric membranous-type basal cell adenoma. 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 cell nests are separated by dense hyaline stroma.
Basal cell adenoma. Membranous type. Salivary gland involvement in this syndrome is characterized by the presence of membranous-type basal cell adenoma, 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.

Q: In Cowden Syndrome, associated tumors and lesions typically demonstrate a loss of immunostaining for [...] due to constitutional pathogenic sequence variants.
PTEN hamartoma tumour syndrome / Cowden syndrome. Adenomatous thyroid nodules in patients with this syndrome show PTEN loss within the lesional follicular cells. Loss of PTEN immunostaining is identified within numerous skin, thyroid, cerebellar, and other lesions associated with Cowden syndrome.
Multiple thyroid adenomatous nodules in Cowden syndrome.
A: PTEN
Back Extra: Cowden Syndrome
- Clinical: Cowden syndrome is characterized by mucocutaneous lesions such as multiple facial trichilemmomas, acral keratoses, and papillomatous papules, as well as an increased risk of cancers, particularly breast, thyroid, and endometrial cancers.
- Micro: Histologically, oral papillomas in Cowden syndrome are indistinguishable from irritation fibromas, consisting of fibrous connective tissue with dilated blood vessels and inflammatory infiltrate, lined by hyperplastic non-keratinizing squamous epithelium.
- Ancillary: Approximately 85% of Cowden syndrome cases are associated with constitutional pathogenic sequence variants in PTEN (10q23.3), and PTEN immunostaining is typically lost in associated lesions.
Reference Gallery:
Oral papilloma in Cowden syndrome. A lesion is shown on the buccal mucosa.
Trichilemmoma in Cowden syndrome. This low-power view shows a small facial trichilemmoma.
Trichilemmoma in Cowden syndrome. Shave excision of a verruca vulgaris–like trichilemmoma.
Oral papilloma in Cowden syndrome. The histology of oral mucosal papillomas in Cowden syndrome is nonspecific and indistinguishable from that of irritation fibroma.
PTEN hamartoma tumour syndrome / Cowden syndrome. Adenomatous thyroid nodules in patients with this syndrome show PTEN loss within the lesional follicular cells. Loss of PTEN immunostaining is identified within numerous skin, thyroid, cerebellar, and other lesions associated with Cowden syndrome.
Multiple thyroid adenomatous nodules in Cowden syndrome.

Q: The characteristic mucocutaneous lesions of Cowden Syndrome include acral keratoses, oral papillomas, and multiple facial [...].
Trichilemmoma in Cowden syndrome. This low-power view shows a small facial trichilemmoma.
Trichilemmoma in Cowden syndrome. Shave excision of a verruca vulgaris–like trichilemmoma.
A: trichilemmomas
Back Extra: Cowden Syndrome
- Clinical: Cowden syndrome is characterized by mucocutaneous lesions such as multiple facial trichilemmomas, acral keratoses, and papillomatous papules, as well as an increased risk of cancers, particularly breast, thyroid, and endometrial cancers.
- Micro: Histologically, oral papillomas in Cowden syndrome are indistinguishable from irritation fibromas, consisting of fibrous connective tissue with dilated blood vessels and inflammatory infiltrate, lined by hyperplastic non-keratinizing squamous epithelium.
- Ancillary: Approximately 85% of Cowden syndrome cases are associated with constitutional pathogenic sequence variants in PTEN (10q23.3), and PTEN immunostaining is typically lost in associated lesions.
Reference Gallery:
Oral papilloma in Cowden syndrome. A lesion is shown on the buccal mucosa.
Trichilemmoma in Cowden syndrome. This low-power view shows a small facial trichilemmoma.
Trichilemmoma in Cowden syndrome. Shave excision of a verruca vulgaris–like trichilemmoma.
Oral papilloma in Cowden syndrome. The histology of oral mucosal papillomas in Cowden syndrome is nonspecific and indistinguishable from that of irritation fibroma.
PTEN hamartoma tumour syndrome / Cowden syndrome. Adenomatous thyroid nodules in patients with this syndrome show PTEN loss within the lesional follicular cells. Loss of PTEN immunostaining is identified within numerous skin, thyroid, cerebellar, and other lesions associated with Cowden syndrome.
Multiple thyroid adenomatous nodules in Cowden syndrome.

Q: Histologically, the oral mucosal papillomas seen in Cowden Syndrome are typically nonspecific and virtually indistinguishable from a(n) [...].
Oral papilloma in Cowden syndrome. A lesion is shown on the buccal mucosa.
Oral papilloma in Cowden syndrome. The histology of oral mucosal papillomas in Cowden syndrome is nonspecific and indistinguishable from that of irritation fibroma.
A: irritation fibroma
Back Extra: Cowden Syndrome
- Clinical: Cowden syndrome is characterized by mucocutaneous lesions such as multiple facial trichilemmomas, acral keratoses, and papillomatous papules, as well as an increased risk of cancers, particularly breast, thyroid, and endometrial cancers.
- Micro: Histologically, oral papillomas in Cowden syndrome are indistinguishable from irritation fibromas, consisting of fibrous connective tissue with dilated blood vessels and inflammatory infiltrate, lined by hyperplastic non-keratinizing squamous epithelium.
- Ancillary: Approximately 85% of Cowden syndrome cases are associated with constitutional pathogenic sequence variants in PTEN (10q23.3), and PTEN immunostaining is typically lost in associated lesions.
Reference Gallery:
Oral papilloma in Cowden syndrome. A lesion is shown on the buccal mucosa.
Trichilemmoma in Cowden syndrome. This low-power view shows a small facial trichilemmoma.
Trichilemmoma in Cowden syndrome. Shave excision of a verruca vulgaris–like trichilemmoma.
Oral papilloma in Cowden syndrome. The histology of oral mucosal papillomas in Cowden syndrome is nonspecific and indistinguishable from that of irritation fibroma.
PTEN hamartoma tumour syndrome / Cowden syndrome. Adenomatous thyroid nodules in patients with this syndrome show PTEN loss within the lesional follicular cells. Loss of PTEN immunostaining is identified within numerous skin, thyroid, cerebellar, and other lesions associated with Cowden syndrome.
Multiple thyroid adenomatous nodules in Cowden syndrome.

Q: The distinctive thyroid tumors that arise in patients with Familial Adenomatous Polyposis are known as [...], which feature anastomosing arches and solid morulae with peculiar nuclear inclusions.
Cribriform-morular thyroid carcinoma. Typical cribriform-morular carcinomas are easily recognized under low-power microscopy. A combination of morular, trabecular, solid, follicular, and spindled patterns of growth can be identified. The cribriform architecture is formed by anastomosing bars or arches 1–2 cell layers thick, and the morular component has peculiar nuclear inclusions.
A: cribriform-morular thyroid carcinomas
Back Extra: Familial Adenomatous Polyposis
- Clinical: Classic Familial Adenomatous Polyposis (FAP) is characterized by the development of >100 adenomatous polyps in the large intestine, with a near-100% risk of colorectal adenocarcinoma by 45 years of age.
- Micro: Thyroid tumours in FAP are cribriform-morular thyroid carcinomas, characterized by a cribriform architecture and the presence of morulae, which are positive for CK5 and CD5 and negative for p63, p40, TTF1, and PAX8.
- Ancillary: Immunohistochemistry shows strong nuclear and cytoplasmic expression of β-catenin in FAP-associated thyroid carcinomas, and molecular studies confirm the presence of APC mutations.
Reference Gallery:
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. The multifocal thyroid carcinomas in familial adenomatous polyposis are those of cribriform-modular thyroid carcinoma. The cribriform component is usually admixed with morulae. Morulae are positive for CK5 (as shown here) and CD5 and are negative for p63, p40, thyroid transcription factor 1 (TTF1), and PAX8.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. The morula cells immunostain for CD5 in a membranous pattern. The scattered CD5-positive T cells are also stained.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. This tumour type, whether or not associated with familial adenomatous polyposis, shows absent staining for thyroglobulin by the tumour cells.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. Another characteristic of the cribriform-morular thyroid carcinoma is the strong nuclear and cytoplasmic expression of β-catenin by the tumour cells.
Cribriform-morular thyroid carcinoma. Typical cribriform-morular carcinomas are easily recognized under low-power microscopy. A combination of morular, trabecular, solid, follicular, and spindled patterns of growth can be identified. The cribriform architecture is formed by anastomosing bars or arches 1–2 cell layers thick, and the morular component has peculiar nuclear inclusions.

Q: In Familial Adenomatous Polyposis, the associated cribriform-morular thyroid carcinomas show characteristic strong nuclear and cytoplasmic immunohistochemical expression of [...] due to underlying APC mutations.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. Another characteristic of the cribriform-morular thyroid carcinoma is the strong nuclear and cytoplasmic expression of β-catenin by the tumour cells.
A: β-catenin
Back Extra: Familial Adenomatous Polyposis
- Clinical: Classic Familial Adenomatous Polyposis (FAP) is characterized by the development of >100 adenomatous polyps in the large intestine, with a near-100% risk of colorectal adenocarcinoma by 45 years of age.
- Micro: Thyroid tumours in FAP are cribriform-morular thyroid carcinomas, characterized by a cribriform architecture and the presence of morulae, which are positive for CK5 and CD5 and negative for p63, p40, TTF1, and PAX8.
- Ancillary: Immunohistochemistry shows strong nuclear and cytoplasmic expression of β-catenin in FAP-associated thyroid carcinomas, and molecular studies confirm the presence of APC mutations.
Reference Gallery:
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. The multifocal thyroid carcinomas in familial adenomatous polyposis are those of cribriform-modular thyroid carcinoma. The cribriform component is usually admixed with morulae. Morulae are positive for CK5 (as shown here) and CD5 and are negative for p63, p40, thyroid transcription factor 1 (TTF1), and PAX8.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. The morula cells immunostain for CD5 in a membranous pattern. The scattered CD5-positive T cells are also stained.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. This tumour type, whether or not associated with familial adenomatous polyposis, shows absent staining for thyroglobulin by the tumour cells.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. Another characteristic of the cribriform-morular thyroid carcinoma is the strong nuclear and cytoplasmic expression of β-catenin by the tumour cells.
Cribriform-morular thyroid carcinoma. Typical cribriform-morular carcinomas are easily recognized under low-power microscopy. A combination of morular, trabecular, solid, follicular, and spindled patterns of growth can be identified. The cribriform architecture is formed by anastomosing bars or arches 1–2 cell layers thick, and the morular component has peculiar nuclear inclusions.

Q: The morular component of the thyroid tumors associated with Familial Adenomatous Polyposis demonstrates characteristic positive immunostaining for [...], but lacks true squamous markers like p40 and p63.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. The multifocal thyroid carcinomas in familial adenomatous polyposis are those of cribriform-modular thyroid carcinoma. The cribriform component is usually admixed with morulae. Morulae are positive for CK5 (as shown here) and CD5 and are negative for p63, p40, thyroid transcription factor 1 (TTF1), and PAX8.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. The morula cells immunostain for CD5 in a membranous pattern. The scattered CD5-positive T cells are also stained.
A: CK5 and CD5
Back Extra: Familial Adenomatous Polyposis
- Clinical: Classic Familial Adenomatous Polyposis (FAP) is characterized by the development of >100 adenomatous polyps in the large intestine, with a near-100% risk of colorectal adenocarcinoma by 45 years of age.
- Micro: Thyroid tumours in FAP are cribriform-morular thyroid carcinomas, characterized by a cribriform architecture and the presence of morulae, which are positive for CK5 and CD5 and negative for p63, p40, TTF1, and PAX8.
- Ancillary: Immunohistochemistry shows strong nuclear and cytoplasmic expression of β-catenin in FAP-associated thyroid carcinomas, and molecular studies confirm the presence of APC mutations.
Reference Gallery:
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. The multifocal thyroid carcinomas in familial adenomatous polyposis are those of cribriform-modular thyroid carcinoma. The cribriform component is usually admixed with morulae. Morulae are positive for CK5 (as shown here) and CD5 and are negative for p63, p40, thyroid transcription factor 1 (TTF1), and PAX8.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. The morula cells immunostain for CD5 in a membranous pattern. The scattered CD5-positive T cells are also stained.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. This tumour type, whether or not associated with familial adenomatous polyposis, shows absent staining for thyroglobulin by the tumour cells.
Familial adenomatous polyposis–associated cribriform-morular thyroid carcinoma. Another characteristic of the cribriform-morular thyroid carcinoma is the strong nuclear and cytoplasmic expression of β-catenin by the tumour cells.
Cribriform-morular thyroid carcinoma. Typical cribriform-morular carcinomas are easily recognized under low-power microscopy. A combination of morular, trabecular, solid, follicular, and spindled patterns of growth can be identified. The cribriform architecture is formed by anastomosing bars or arches 1–2 cell layers thick, and the morular component has peculiar nuclear inclusions.

Q: Head and neck squamous cell carcinomas in patients with Fanconi Anaemia frequently present as poorly differentiated tumors that undergo [...], which can be histologically highlighted by vimentin positivity in the spindle cell population.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Poorly differentiated with focal sarcomatoid changes.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Vimentin immunostaining within the spindle cell population, highlighting the epithelial–mesenchymal transition.
A: epithelial-mesenchymal transition
Back Extra: Fanconi Anaemia
- Clinical: Fanconi anaemia is characterized by premature ageing, short stature, microcephaly, and a predisposition to haematological and solid malignancies.
- Micro: FA-related HNSCCs frequently present as poorly differentiated tumours with epithelial–mesenchymal transition and a higher proportion of cancer stem cells.
- Ancillary: The diagnosis of Fanconi anaemia is confirmed by diepoxybutane (DEB)- or mitomycin C–induced formation of triradial and quadriradial figures in chromosome spreads from lymphocytes.
Reference Gallery:
Fanconi anaemia. Leukoplakia of the tongue in a patient with Fanconi anaemia.
Fanconi anaemia. Lichenoid keratosis of the tongue in a patient with Fanconi anaemia.
Fanconi anaemia. Squamous cell carcinoma of the tongue presenting as a non-healing ulcer in a patient with Fanconi anaemia.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Poorly differentiated with focal sarcomatoid changes.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Vimentin immunostaining within the spindle cell population, highlighting the epithelial–mesenchymal transition.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Immunostaining for ALDH1 in the cancer stem cells.

Q: The diagnosis of Fanconi Anaemia (which predisposes to premature aging, short stature, and oral squamous cell carcinomas, as shown) is confirmed by demonstrating triradial and quadriradial chromosomal figures in lymphocytes induced by mitomycin C or [...].
Fanconi anaemia. Squamous cell carcinoma of the tongue presenting as a non-healing ulcer in a patient with Fanconi anaemia.
A: diepoxybutane (DEB)
Back Extra: Fanconi Anaemia
- Clinical: Fanconi anaemia is characterized by premature ageing, short stature, microcephaly, and a predisposition to haematological and solid malignancies.
- Micro: FA-related HNSCCs frequently present as poorly differentiated tumours with epithelial–mesenchymal transition and a higher proportion of cancer stem cells.
- Ancillary: The diagnosis of Fanconi anaemia is confirmed by diepoxybutane (DEB)- or mitomycin C–induced formation of triradial and quadriradial figures in chromosome spreads from lymphocytes.
Reference Gallery:
Fanconi anaemia. Leukoplakia of the tongue in a patient with Fanconi anaemia.
Fanconi anaemia. Lichenoid keratosis of the tongue in a patient with Fanconi anaemia.
Fanconi anaemia. Squamous cell carcinoma of the tongue presenting as a non-healing ulcer in a patient with Fanconi anaemia.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Poorly differentiated with focal sarcomatoid changes.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Vimentin immunostaining within the spindle cell population, highlighting the epithelial–mesenchymal transition.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Immunostaining for ALDH1 in the cancer stem cells.

Q: In Fanconi Anaemia, the associated head and neck squamous cell carcinomas frequently exhibit a higher proportion of cancer stem cells, which can be explicitly highlighted by immunostaining for [...].
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Immunostaining for ALDH1 in the cancer stem cells.
A: ALDH1
Back Extra: Fanconi Anaemia
- Clinical: Fanconi anaemia is characterized by premature ageing, short stature, microcephaly, and a predisposition to haematological and solid malignancies.
- Micro: FA-related HNSCCs frequently present as poorly differentiated tumours with epithelial–mesenchymal transition and a higher proportion of cancer stem cells.
- Ancillary: The diagnosis of Fanconi anaemia is confirmed by diepoxybutane (DEB)- or mitomycin C–induced formation of triradial and quadriradial figures in chromosome spreads from lymphocytes.
Reference Gallery:
Fanconi anaemia. Leukoplakia of the tongue in a patient with Fanconi anaemia.
Fanconi anaemia. Lichenoid keratosis of the tongue in a patient with Fanconi anaemia.
Fanconi anaemia. Squamous cell carcinoma of the tongue presenting as a non-healing ulcer in a patient with Fanconi anaemia.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Poorly differentiated with focal sarcomatoid changes.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Vimentin immunostaining within the spindle cell population, highlighting the epithelial–mesenchymal transition.
Fanconi anaemia. Tongue squamous cell carcinoma in a patient with Fanconi anaemia. Immunostaining for ALDH1 in the cancer stem cells.

Q: Parathyroid tumors associated with Hyperparathyroidism-Jaw Tumor Syndrome characteristically exhibit loss of [...] expression on immunohistochemistry.
Parafibromin-deficient parathyroid tumour. Cytological features include nuclear enlargement often with preserved N:C ratios, multinucleation, perinuclear cytoplasmic clearing, and eosinophilic cell type, sometimes with a glassy quality.
Parafibromin-deficient parathyroid tumour. It is emphasized that for parafibromin immunohistochemistry to be considered negative there should be an internal positive control in non-neoplastic cells including non-neoplastic parathyroid tissue.
A: parafibromin
Back Extra: Hyperparathyroidism-Jaw Tumour Syndrome
- Clinical: Patients with Hyperparathyroidism-Jaw Tumour Syndrome often present with primary hyperparathyroidism, large parathyroid tumours, and severe hypercalcaemia, particularly in those under 40 years old.
- Micro: Parafibromin-deficient parathyroid tumours in Hyperparathyroidism-Jaw Tumour Syndrome show a sheet-like growth pattern, eosinophilic cytoplasm, and perinuclear cytoplasmic clearing.
- Ancillary: Loss of parafibromin expression on immunohistochemistry is a key diagnostic feature in parathyroid tumours associated with Hyperparathyroidism-Jaw Tumour Syndrome.
Reference Gallery:
Ossifying fibroma arising in hyperparathyroidism–jaw tumour syndrome. There is an avascular hypercellular stroma composed of bland spindled cells surrounding bony trabeculae (low-power view).
Ossifying fibroma arising in hyperparathyroidism–jaw tumour syndrome. High-power view of an avascular hypercellular stroma composed of bland spindled cells surrounding bony trabeculae.
Parafibromin-deficient parathyroid tumour. Cytological features include nuclear enlargement often with preserved N:C ratios, multinucleation, perinuclear cytoplasmic clearing, and eosinophilic cell type, sometimes with a glassy quality.
Parafibromin-deficient parathyroid tumour. It is emphasized that for parafibromin immunohistochemistry to be considered negative there should be an internal positive control in non-neoplastic cells including non-neoplastic parathyroid tissue.

Q: The characteristic fibro-osseous jaw lesions seen in patients with Hyperparathyroidism-Jaw Tumor Syndrome are histologically classified as [...], which consist of an avascular hypercellular stroma surrounding bony trabeculae.
Ossifying fibroma arising in hyperparathyroidism–jaw tumour syndrome. There is an avascular hypercellular stroma composed of bland spindled cells surrounding bony trabeculae (low-power view).
Ossifying fibroma arising in hyperparathyroidism–jaw tumour syndrome. High-power view of an avascular hypercellular stroma composed of bland spindled cells surrounding bony trabeculae.
A: ossifying fibromas
Back Extra: Hyperparathyroidism-Jaw Tumour Syndrome
- Clinical: Patients with Hyperparathyroidism-Jaw Tumour Syndrome often present with primary hyperparathyroidism, large parathyroid tumours, and severe hypercalcaemia, particularly in those under 40 years old.
- Micro: Parafibromin-deficient parathyroid tumours in Hyperparathyroidism-Jaw Tumour Syndrome show a sheet-like growth pattern, eosinophilic cytoplasm, and perinuclear cytoplasmic clearing.
- Ancillary: Loss of parafibromin expression on immunohistochemistry is a key diagnostic feature in parathyroid tumours associated with Hyperparathyroidism-Jaw Tumour Syndrome.
Reference Gallery:
Ossifying fibroma arising in hyperparathyroidism–jaw tumour syndrome. There is an avascular hypercellular stroma composed of bland spindled cells surrounding bony trabeculae (low-power view).
Ossifying fibroma arising in hyperparathyroidism–jaw tumour syndrome. High-power view of an avascular hypercellular stroma composed of bland spindled cells surrounding bony trabeculae.
Parafibromin-deficient parathyroid tumour. Cytological features include nuclear enlargement often with preserved N:C ratios, multinucleation, perinuclear cytoplasmic clearing, and eosinophilic cell type, sometimes with a glassy quality.
Parafibromin-deficient parathyroid tumour. It is emphasized that for parafibromin immunohistochemistry to be considered negative there should be an internal positive control in non-neoplastic cells including non-neoplastic parathyroid tissue.

Q: Patients with the 2B subtype of Multiple Endocrine Neoplasia Type 2 classically present with a marfanoid habitus and characteristic [...] (such as the one shown on the patient's tongue).
Multiple endocrine neoplasia type 2. A 21-year-old man with MEN2 with a tongue mucosal neuroma.
A: mucosal neuromas
Back Extra: Multiple Endocrine Neoplasia Type 2
- Clinical: Multiple Endocrine Neoplasia Type 2 (MEN2) is characterized by the development of medullary thyroid carcinoma (MTC), often associated with phaeochromocytoma and/or parathyroid proliferations. MEN2B can present with a marfanoid habitus and mucosal neuromas.
- Micro: MTC in MEN2 appears histologically similar to sporadic MTC but is more often multifocal and bilateral, with associated nodular C-cell hyperplasia. Parathyroid proliferations in MEN2A are classified as adenomas or hyperplasia.
- Ancillary: Diagnosis of MEN2 is confirmed by identifying a constitutional pathogenic sequence variant in the RET gene. Common mutations include RET p.C634R in MEN2A and RET p.M918T in MEN2B.
Reference Gallery:
Multiple endocrine neoplasia type 2. A 21-year-old man with MEN2 with a tongue mucosal neuroma.

Q: The diagnosis of Multiple Endocrine Neoplasia Type 2 is genetically confirmed by identifying a constitutional pathogenic sequence variant in the [...] proto-oncogene.
Multiple endocrine neoplasia type 2. A 21-year-old man with MEN2 with a tongue mucosal neuroma.
A: RET
Back Extra: Multiple Endocrine Neoplasia Type 2
- Clinical: Multiple Endocrine Neoplasia Type 2 (MEN2) is characterized by the development of medullary thyroid carcinoma (MTC), often associated with phaeochromocytoma and/or parathyroid proliferations. MEN2B can present with a marfanoid habitus and mucosal neuromas.
- Micro: MTC in MEN2 appears histologically similar to sporadic MTC but is more often multifocal and bilateral, with associated nodular C-cell hyperplasia. Parathyroid proliferations in MEN2A are classified as adenomas or hyperplasia.
- Ancillary: Diagnosis of MEN2 is confirmed by identifying a constitutional pathogenic sequence variant in the RET gene. Common mutations include RET p.C634R in MEN2A and RET p.M918T in MEN2B.
Reference Gallery:
Multiple endocrine neoplasia type 2. A 21-year-old man with MEN2 with a tongue mucosal neuroma.

Q: Patients with Neurofibromatosis Type 1 frequently present clinically with numerous cutaneous neurofibromas, skinfold freckling, and multiple pigmented skin lesions known as [...] macules.
Orbitofacial neurofibromatosis type 1. This is a unique clinical variant that affects the bone and soft tissues of the orbital region and may result in profound asymmetry. Café-au-lait spots and conventional cutaneous neurofibromas are also present in this patient.
A: café-au-lait
Back Extra: Neurofibromatosis Type 1
- Clinical: Multiple café-au-lait macules, skinfold freckling, and cutaneous neurofibromas are common in patients with Neurofibromatosis Type 1.
- Micro: Neurofibromas in Neurofibromatosis Type 1 are characterized by the presence of cells of the haematopoietic lineage, including histiocytes and mast cells.
- Ancillary: A pathogenic NF1 variant is detected in 95% of people with Neurofibromatosis Type 1, and additional genetic alterations are often seen in atypical neurofibromatous neoplasms.
Reference Gallery:
Orbitofacial neurofibromatosis type 1. This is a unique clinical variant that affects the bone and soft tissues of the orbital region and may result in profound asymmetry. Café-au-lait spots and conventional cutaneous neurofibromas are also present in this patient.
Orbitofacial neurofibroma. Orbital neurofibromas frequently have plexiform components and may intimately involve ocular adnexa, such as the lacrimal gland as in this example.
Orbitofacial neurofibroma. Orbitofacial neurofibromas frequently have coexisting plexiform and diffuse components.
Cutaneous neurofibroma. Cutaneous neurofibromas often involve the face and scalp in patients with neurofibromatosis type 1 and resemble their sporadic counterparts.
Malignant peripheral nerve sheath tumour. These tumours are relatively rare in the head and neck region. This low-grade tumour developed in progression from an orbitofacial neurofibroma in a patient with neurofibromatosis type 1.
Orbitofacial neurofibromatosis type 1. Axial CT using bone windows highlights prominent bone remodelling, facial neurofibromatosis, and proptosis associated with a large orbital neurofibroma in a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour. Malignant transformation in the form of a rapidly enlarging nodule (arrows) within a plexiform neurofibroma of the posterior scalp of a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour. High cellularity and mitotic activity characterize this tumour developing in the posterior scalp of a patient with neurofibromatosis type 1 within a longstanding plexiform neurofibroma.

Q: In Neurofibromatosis Type 1, deeply seated or orbitofacial neurofibromas frequently exhibit a characteristic, multinodular [...] architecture, which may intimately involve local structures and coexist with diffuse components.
Orbitofacial neurofibroma. Orbital neurofibromas frequently have plexiform components and may intimately involve ocular adnexa, such as the lacrimal gland as in this example.
Orbitofacial neurofibroma. Orbitofacial neurofibromas frequently have coexisting plexiform and diffuse components.
A: plexiform
Back Extra: Neurofibromatosis Type 1
- Clinical: Multiple café-au-lait macules, skinfold freckling, and cutaneous neurofibromas are common in patients with Neurofibromatosis Type 1.
- Micro: Neurofibromas in Neurofibromatosis Type 1 are characterized by the presence of cells of the haematopoietic lineage, including histiocytes and mast cells.
- Ancillary: A pathogenic NF1 variant is detected in 95% of people with Neurofibromatosis Type 1, and additional genetic alterations are often seen in atypical neurofibromatous neoplasms.
Reference Gallery:
Orbitofacial neurofibromatosis type 1. This is a unique clinical variant that affects the bone and soft tissues of the orbital region and may result in profound asymmetry. Café-au-lait spots and conventional cutaneous neurofibromas are also present in this patient.
Orbitofacial neurofibroma. Orbital neurofibromas frequently have plexiform components and may intimately involve ocular adnexa, such as the lacrimal gland as in this example.
Orbitofacial neurofibroma. Orbitofacial neurofibromas frequently have coexisting plexiform and diffuse components.
Cutaneous neurofibroma. Cutaneous neurofibromas often involve the face and scalp in patients with neurofibromatosis type 1 and resemble their sporadic counterparts.
Malignant peripheral nerve sheath tumour. These tumours are relatively rare in the head and neck region. This low-grade tumour developed in progression from an orbitofacial neurofibroma in a patient with neurofibromatosis type 1.
Orbitofacial neurofibromatosis type 1. Axial CT using bone windows highlights prominent bone remodelling, facial neurofibromatosis, and proptosis associated with a large orbital neurofibroma in a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour. Malignant transformation in the form of a rapidly enlarging nodule (arrows) within a plexiform neurofibroma of the posterior scalp of a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour. High cellularity and mitotic activity characterize this tumour developing in the posterior scalp of a patient with neurofibromatosis type 1 within a longstanding plexiform neurofibroma.

Q: A major and potentially lethal complication of Neurofibromatosis Type 1 is the malignant transformation of a longstanding plexiform neurofibroma into a highly cellular, mitotically active [...].
Malignant peripheral nerve sheath tumour. Malignant transformation in the form of a rapidly enlarging nodule (arrows) within a plexiform neurofibroma of the posterior scalp of a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour. High cellularity and mitotic activity characterize this tumour developing in the posterior scalp of a patient with neurofibromatosis type 1 within a longstanding plexiform neurofibroma.
A: malignant peripheral nerve sheath tumor
Back Extra: Neurofibromatosis Type 1
- Clinical: Multiple café-au-lait macules, skinfold freckling, and cutaneous neurofibromas are common in patients with Neurofibromatosis Type 1.
- Micro: Neurofibromas in Neurofibromatosis Type 1 are characterized by the presence of cells of the haematopoietic lineage, including histiocytes and mast cells.
- Ancillary: A pathogenic NF1 variant is detected in 95% of people with Neurofibromatosis Type 1, and additional genetic alterations are often seen in atypical neurofibromatous neoplasms.
Reference Gallery:
Orbitofacial neurofibromatosis type 1. This is a unique clinical variant that affects the bone and soft tissues of the orbital region and may result in profound asymmetry. Café-au-lait spots and conventional cutaneous neurofibromas are also present in this patient.
Orbitofacial neurofibroma. Orbital neurofibromas frequently have plexiform components and may intimately involve ocular adnexa, such as the lacrimal gland as in this example.
Orbitofacial neurofibroma. Orbitofacial neurofibromas frequently have coexisting plexiform and diffuse components.
Cutaneous neurofibroma. Cutaneous neurofibromas often involve the face and scalp in patients with neurofibromatosis type 1 and resemble their sporadic counterparts.
Malignant peripheral nerve sheath tumour. These tumours are relatively rare in the head and neck region. This low-grade tumour developed in progression from an orbitofacial neurofibroma in a patient with neurofibromatosis type 1.
Orbitofacial neurofibromatosis type 1. Axial CT using bone windows highlights prominent bone remodelling, facial neurofibromatosis, and proptosis associated with a large orbital neurofibroma in a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour. Malignant transformation in the form of a rapidly enlarging nodule (arrows) within a plexiform neurofibroma of the posterior scalp of a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour. High cellularity and mitotic activity characterize this tumour developing in the posterior scalp of a patient with neurofibromatosis type 1 within a longstanding plexiform neurofibroma.

Q: A hallmark clinical and radiologic finding in Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) is the presence of multiple [...] in the jaws, which frequently displace developing molars.
Naevoid basal cell carcinoma syndrome, multiple odontogenic keratocysts. Panoramic radiograph of a 13-year-old child, showing four large odontogenic keratocysts, one in each jaw quadrant posteriorly, displacing the developing third molars and upper second molars.
A: odontogenic keratocysts
Back Extra: Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
- Clinical: Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) is characterized by multiple basal cell carcinomas and odontogenic keratocysts, often evident by the age of 40.
- Micro: Odontogenic keratocysts in Gorlin Syndrome have a cyst lining with surface parakeratosis and hyperchromatic basal cell nuclei.
- Ancillary: Genetic testing for mutations in PTCH1 and SUFU is crucial for the diagnosis and management of Naevoid Basal Cell Carcinoma Syndrome.
Reference Gallery:
Naevoid basal cell carcinoma syndrome, multiple odontogenic keratocysts. Panoramic radiograph of a 13-year-old child, showing four large odontogenic keratocysts, one in each jaw quadrant posteriorly, displacing the developing third molars and upper second molars.
Odontogenic keratocyst. Cyst wall lined by uniform epithelium (stratified squamous type) without rete ridges but with hyperchromatic palisaded basal cell nuclei and characteristic corrugated surface parakeratin.
Odontogenic keratocyst. The epithelial cyst lining displays surface parakeratosis, cuboidal to columnar basal cells with hyperchromatic nuclei, and focal reverse nuclear polarity.

Q: The characteristic jaw cysts of Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) demonstrate a stratified squamous epithelial lining with palisaded, hyperchromatic basal cells and a corrugated surface layer of [...].
Odontogenic keratocyst. Cyst wall lined by uniform epithelium (stratified squamous type) without rete ridges but with hyperchromatic palisaded basal cell nuclei and characteristic corrugated surface parakeratin.
Odontogenic keratocyst. The epithelial cyst lining displays surface parakeratosis, cuboidal to columnar basal cells with hyperchromatic nuclei, and focal reverse nuclear polarity.
A: parakeratin
Back Extra: Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
- Clinical: Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) is characterized by multiple basal cell carcinomas and odontogenic keratocysts, often evident by the age of 40.
- Micro: Odontogenic keratocysts in Gorlin Syndrome have a cyst lining with surface parakeratosis and hyperchromatic basal cell nuclei.
- Ancillary: Genetic testing for mutations in PTCH1 and SUFU is crucial for the diagnosis and management of Naevoid Basal Cell Carcinoma Syndrome.
Reference Gallery:
Naevoid basal cell carcinoma syndrome, multiple odontogenic keratocysts. Panoramic radiograph of a 13-year-old child, showing four large odontogenic keratocysts, one in each jaw quadrant posteriorly, displacing the developing third molars and upper second molars.
Odontogenic keratocyst. Cyst wall lined by uniform epithelium (stratified squamous type) without rete ridges but with hyperchromatic palisaded basal cell nuclei and characteristic corrugated surface parakeratin.
Odontogenic keratocyst. The epithelial cyst lining displays surface parakeratosis, cuboidal to columnar basal cells with hyperchromatic nuclei, and focal reverse nuclear polarity.

Q: Patients with Tuberous Sclerosis commonly present with facial and oral [...], which form well-circumscribed, fibrotic vascular nodules characterized microscopically by increased vessel density and mural sclerosis.
Oral angiofibroma. Oral angiofibromas affecting the superior and inferior anterior gingiva.
Facial angiofibroma. Angiofibromas when large can form fibrotic vascular polypoid masses with a predilection for the face in patients with tuberous sclerosis (H&E).
Facial angiofibroma. An increase in vessel density with associated mural and stromal sclerosis characterizes angiofibromas in tuberous sclerosis.
A: angiofibromas
Back Extra: Tuberous Sclerosis
- Clinical: Cardiac rhabdomyomas are often a presenting feature of tuberous sclerosis in newborns and infants aged < 2 years.
- Micro: Angiofibromas form well-circumscribed nodules composed of bland oval cells, with delicate collagen deposition and evenly distributed small to medium-sized vessels.
- Ancillary: Genetic testing for TSC1 or TSC2 mutations is recommended for family members of an affected patient, especially in infants, and may also be offered as a preimplantation or prenatal test.
Reference Gallery:
Oral angiofibroma. Oral angiofibromas affecting the superior and inferior anterior gingiva.
Facial angiofibroma. Angiofibromas when large can form fibrotic vascular polypoid masses with a predilection for the face in patients with tuberous sclerosis (H&E).
Facial angiofibroma. An increase in vessel density with associated mural and stromal sclerosis characterizes angiofibromas in tuberous sclerosis.
Facial angiofibroma. Stromal multinucleated fibroblasts may be present in angiofibromas of patients with tuberous sclerosis and lack prognostic significance.

Q: In Tuberous Sclerosis, the characteristic angiofibromas may histologically demonstrate distinctive [...] scattered within the stroma, which are a morphological feature lacking prognostic significance.
Facial angiofibroma. Stromal multinucleated fibroblasts may be present in angiofibromas of patients with tuberous sclerosis and lack prognostic significance.
A: multinucleated fibroblasts
Back Extra: Tuberous Sclerosis
- Clinical: Cardiac rhabdomyomas are often a presenting feature of tuberous sclerosis in newborns and infants aged < 2 years.
- Micro: Angiofibromas form well-circumscribed nodules composed of bland oval cells, with delicate collagen deposition and evenly distributed small to medium-sized vessels.
- Ancillary: Genetic testing for TSC1 or TSC2 mutations is recommended for family members of an affected patient, especially in infants, and may also be offered as a preimplantation or prenatal test.
Reference Gallery:
Oral angiofibroma. Oral angiofibromas affecting the superior and inferior anterior gingiva.
Facial angiofibroma. Angiofibromas when large can form fibrotic vascular polypoid masses with a predilection for the face in patients with tuberous sclerosis (H&E).
Facial angiofibroma. An increase in vessel density with associated mural and stromal sclerosis characterizes angiofibromas in tuberous sclerosis.
Facial angiofibroma. Stromal multinucleated fibroblasts may be present in angiofibromas of patients with tuberous sclerosis and lack prognostic significance.

Q: In Von Hippel-Lindau Syndrome, a characteristic ear lesion is the [...], which microscopically exhibits single layers of low cuboidal to columnar cells forming papillary projections and cystic spaces containing colloid-like secretions.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. There is a colloid-like secretion in the cystic spaces.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. The neoplastic cells show a low cuboidal to columnar cell appearance, lining papillary projections and dilated cystic spaces.
A: endolymphatic sac tumor
Back Extra: Von Hippel-Lindau Syndrome
- Clinical: Neurological manifestations often begin with decreased visual acuity and can include cerebellar ataxia and spinal cord compression from haemangioblastomas.
- Micro: Ear endolymphatic sac tumours (ELSTs) are characterized by a single layer of low cuboidal to columnar cells arranged in papillary projections with fibrovascular cores, and cystic spaces containing serum, secretions, and/or erythrocytes.
- Ancillary: Neoplastic cells in ELSTs are positive for pancytokeratin, CK7, HIF1α, EMA, GLUT1, CAIX (membranous), and PAX8 (nuclear), and negative for TTF1, thyroglobulin, PSA, CD10, AMACR (P504S), p63, synaptophysin, GATA3, and RCCm.
Reference Gallery:
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. There is a colloid-like secretion in the cystic spaces.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. The neoplastic cells show a low cuboidal to columnar cell appearance, lining papillary projections and dilated cystic spaces.

Q: A [...] is a type of Germ Cell Tumor that is histologically characterized by the haphazard arrangement of tissues derived from all three germ layers (endoderm, mesoderm, and ectoderm).
Teratoma. Mature cartilage adjacent to more primitive mesenchyme in a mature teratoma.
Teratoma. Cartilage juxtaposed to various epithelia in a haphazard arrangement. Primitive blastema-type tissue is noted (upper left).
A: teratoma
Back Extra: Germ Cell Tumor
- Clinical: Teratomas in the head and neck can present as mass lesions, often causing nasal obstruction and facial deformity.
- Micro: Teratomas are characterized by the presence of tissues from all three germ layers (endoderm, mesoderm, and ectoderm), often with cystic spaces lined by various epithelial types.
- Ancillary: Yolk sac tumours are positive for AFP, α1-antitrypsin, SALL4, and glypican-3 (GPC3).
Reference Gallery:
Teratoma. A neonate had a midline maxilla pedunculated mass that protruded out of the mouth. Histologically this was a mature teratoma.
Teratoma. A sagittal T1 spin echo image of a large mass filling the nasopharynx, representing an immature teratoma.
Teratoma. An axial T2-weighted fat-suppressed image shows the same immature teratoma, with the characteristic bright signal.
Malignant teratoma. Ultrasound shows a 36.7 mm midline anterior neck mass that extended into the floor of the mouth. Histologically, this represented a malignant teratoma.
Teratoma. Mature cartilage adjacent to more primitive mesenchyme in a mature teratoma.
Teratoma. Cartilage juxtaposed to various epithelia in a haphazard arrangement. Primitive blastema-type tissue is noted (upper left).
Teratoma. Cysts lined by low cuboidal epithelium are subtended by primitive-appearing muscle tissue.
Yolk sac tumour. The histological features of yolk sac tumour are seen in this sinonasal tract lesion. Note the numerous globules in this field.
Yolk sac tumour. A Schiller–Duval body is seen, with a projection into the lumen. The neoplastic cells show cleared cytoplasm and a high N:C ratio.
Yolk sac tumour. The globules are highlighted by AFP (shown here) or α1-antitrypsin.

Q: The yolk sac tumor is a highly malignant subtype of Germ Cell Tumor that may histologically feature a central capillary surrounded by neoplastic cells projecting into a cystic space, a pathognomonic structure classically termed a [...].
Yolk sac tumour. A Schiller–Duval body is seen, with a projection into the lumen. The neoplastic cells show cleared cytoplasm and a high N:C ratio.
A: Schiller-Duval body
Back Extra: Germ Cell Tumor
- Clinical: Teratomas in the head and neck can present as mass lesions, often causing nasal obstruction and facial deformity.
- Micro: Teratomas are characterized by the presence of tissues from all three germ layers (endoderm, mesoderm, and ectoderm), often with cystic spaces lined by various epithelial types.
- Ancillary: Yolk sac tumours are positive for AFP, α1-antitrypsin, SALL4, and glypican-3 (GPC3).
Reference Gallery:
Teratoma. A neonate had a midline maxilla pedunculated mass that protruded out of the mouth. Histologically this was a mature teratoma.
Teratoma. A sagittal T1 spin echo image of a large mass filling the nasopharynx, representing an immature teratoma.
Teratoma. An axial T2-weighted fat-suppressed image shows the same immature teratoma, with the characteristic bright signal.
Malignant teratoma. Ultrasound shows a 36.7 mm midline anterior neck mass that extended into the floor of the mouth. Histologically, this represented a malignant teratoma.
Teratoma. Mature cartilage adjacent to more primitive mesenchyme in a mature teratoma.
Teratoma. Cartilage juxtaposed to various epithelia in a haphazard arrangement. Primitive blastema-type tissue is noted (upper left).
Teratoma. Cysts lined by low cuboidal epithelium are subtended by primitive-appearing muscle tissue.
Yolk sac tumour. The histological features of yolk sac tumour are seen in this sinonasal tract lesion. Note the numerous globules in this field.
Yolk sac tumour. A Schiller–Duval body is seen, with a projection into the lumen. The neoplastic cells show cleared cytoplasm and a high N:C ratio.
Yolk sac tumour. The globules are highlighted by AFP (shown here) or α1-antitrypsin.

Q: The yolk sac subtype of Germ Cell Tumor often contains intracytoplasmic eosinophilic globules that demonstrate characteristic immunohistochemical positivity for [...] (AFP) and alpha-1-antitrypsin.
Yolk sac tumour. The histological features of yolk sac tumour are seen in this sinonasal tract lesion. Note the numerous globules in this field.
Yolk sac tumour. The globules are highlighted by AFP (shown here) or α1-antitrypsin.
A: alpha-fetoprotein
Back Extra: Germ Cell Tumor
- Clinical: Teratomas in the head and neck can present as mass lesions, often causing nasal obstruction and facial deformity.
- Micro: Teratomas are characterized by the presence of tissues from all three germ layers (endoderm, mesoderm, and ectoderm), often with cystic spaces lined by various epithelial types.
- Ancillary: Yolk sac tumours are positive for AFP, α1-antitrypsin, SALL4, and glypican-3 (GPC3).
Reference Gallery:
Teratoma. A neonate had a midline maxilla pedunculated mass that protruded out of the mouth. Histologically this was a mature teratoma.
Teratoma. A sagittal T1 spin echo image of a large mass filling the nasopharynx, representing an immature teratoma.
Teratoma. An axial T2-weighted fat-suppressed image shows the same immature teratoma, with the characteristic bright signal.
Malignant teratoma. Ultrasound shows a 36.7 mm midline anterior neck mass that extended into the floor of the mouth. Histologically, this represented a malignant teratoma.
Teratoma. Mature cartilage adjacent to more primitive mesenchyme in a mature teratoma.
Teratoma. Cartilage juxtaposed to various epithelia in a haphazard arrangement. Primitive blastema-type tissue is noted (upper left).
Teratoma. Cysts lined by low cuboidal epithelium are subtended by primitive-appearing muscle tissue.
Yolk sac tumour. The histological features of yolk sac tumour are seen in this sinonasal tract lesion. Note the numerous globules in this field.
Yolk sac tumour. A Schiller–Duval body is seen, with a projection into the lumen. The neoplastic cells show cleared cytoplasm and a high N:C ratio.
Yolk sac tumour. The globules are highlighted by AFP (shown here) or α1-antitrypsin.

Q: Microscopically, Burkitt Lymphoma exhibits a diffuse proliferation of intermediate-sized monomorphic lymphoma cells that create a characteristic [...] pattern.
Burkitt lymphoma, oral cavity. There are small to medium-sized monomorphic lymphoid cells, with multiple small nucleoli, cohesive growth, and a starry-sky pattern.
Sporadic Burkitt lymphoma. This case of Burkitt lymphoma involved the nasopharynx. A starry-sky pattern is present and the lymphoma cells are monomorphic and of intermediate size.
A: starry-sky
Back Extra: Burkitt Lymphoma
- Clinical: Patients with Burkitt lymphoma often present with extranodal disease, a high tumour burden, and a short duration of symptoms.
- Micro: The morphological features of Burkitt lymphoma include a diffuse proliferation of intermediate-sized lymphoma cells with a starry-sky pattern.
- Ancillary: MYC translocations, particularly t(8;14)(q24;q32), are a hallmark of Burkitt lymphoma and are present in 80% of cases.
Reference Gallery:
Burkitt lymphoma, oral cavity. The lymphoma involves the submucosa, forming a dense infiltrate.
Burkitt lymphoma, oral cavity. There are small to medium-sized monomorphic lymphoid cells, with multiple small nucleoli, cohesive growth, and a starry-sky pattern.
Sporadic Burkitt lymphoma. This case of Burkitt lymphoma involved the nasopharynx. A starry-sky pattern is present and the lymphoma cells are monomorphic and of intermediate size.
Sporadic Burkitt lymphoma. Virtually all of the lymphoma cells are proliferating, as shown by Ki-67 immunohistochemistry.
Sporadic Burkitt lymphoma. The lymphoma cells are monomorphic with numerous cytoplasmic vacuoles, as seen on this cytospin preparation of a fine-needle aspirate stained with Giemsa.
Immunodeficiency-associated Burkitt lymphoma. This Burkitt lymphoma involving cervical lymph nodes developed in a man with HIV infection. The neoplasm has a prominent starry-sky pattern.
Immunodeficiency-associated Burkitt lymphoma. High-magnification view of Burkitt lymphoma involving cervical lymph nodes in a man with HIV infection. The lymphoma cells are monomorphic and of intermediate size, with multiple small nucleoli.
Immunodeficiency-associated Burkitt lymphoma. In this case of HIV-associated Burkitt lymphoma, virtually all of the cells were positive for EBV infection (in situ hybridization for EBV-encoded small RNA [EBER] with eosin counterstain).
Endemic Burkitt lymphoma. An African boy with Burkitt lymphoma involving his maxillary region.

Q: Due to its rapid growth and high tumor burden, Burkitt Lymphoma demonstrates a near 100% proliferation fraction when assessed with [...] immunohistochemistry.
Sporadic Burkitt lymphoma. Virtually all of the lymphoma cells are proliferating, as shown by Ki-67 immunohistochemistry.
A: Ki-67
Back Extra: Burkitt Lymphoma
- Clinical: Patients with Burkitt lymphoma often present with extranodal disease, a high tumour burden, and a short duration of symptoms.
- Micro: The morphological features of Burkitt lymphoma include a diffuse proliferation of intermediate-sized lymphoma cells with a starry-sky pattern.
- Ancillary: MYC translocations, particularly t(8;14)(q24;q32), are a hallmark of Burkitt lymphoma and are present in 80% of cases.
Reference Gallery:
Burkitt lymphoma, oral cavity. The lymphoma involves the submucosa, forming a dense infiltrate.
Burkitt lymphoma, oral cavity. There are small to medium-sized monomorphic lymphoid cells, with multiple small nucleoli, cohesive growth, and a starry-sky pattern.
Sporadic Burkitt lymphoma. This case of Burkitt lymphoma involved the nasopharynx. A starry-sky pattern is present and the lymphoma cells are monomorphic and of intermediate size.
Sporadic Burkitt lymphoma. Virtually all of the lymphoma cells are proliferating, as shown by Ki-67 immunohistochemistry.
Sporadic Burkitt lymphoma. The lymphoma cells are monomorphic with numerous cytoplasmic vacuoles, as seen on this cytospin preparation of a fine-needle aspirate stained with Giemsa.
Immunodeficiency-associated Burkitt lymphoma. This Burkitt lymphoma involving cervical lymph nodes developed in a man with HIV infection. The neoplasm has a prominent starry-sky pattern.
Immunodeficiency-associated Burkitt lymphoma. High-magnification view of Burkitt lymphoma involving cervical lymph nodes in a man with HIV infection. The lymphoma cells are monomorphic and of intermediate size, with multiple small nucleoli.
Immunodeficiency-associated Burkitt lymphoma. In this case of HIV-associated Burkitt lymphoma, virtually all of the cells were positive for EBV infection (in situ hybridization for EBV-encoded small RNA [EBER] with eosin counterstain).
Endemic Burkitt lymphoma. An African boy with Burkitt lymphoma involving his maxillary region.

Q: The endemic clinical variant of Burkitt Lymphoma often presents as an extranodal tumor classically involving the [...] region or jaw in African children.
Endemic Burkitt lymphoma. An African boy with Burkitt lymphoma involving his maxillary region.
A: maxillary
Back Extra: Burkitt Lymphoma
- Clinical: Patients with Burkitt lymphoma often present with extranodal disease, a high tumour burden, and a short duration of symptoms.
- Micro: The morphological features of Burkitt lymphoma include a diffuse proliferation of intermediate-sized lymphoma cells with a starry-sky pattern.
- Ancillary: MYC translocations, particularly t(8;14)(q24;q32), are a hallmark of Burkitt lymphoma and are present in 80% of cases.
Reference Gallery:
Burkitt lymphoma, oral cavity. The lymphoma involves the submucosa, forming a dense infiltrate.
Burkitt lymphoma, oral cavity. There are small to medium-sized monomorphic lymphoid cells, with multiple small nucleoli, cohesive growth, and a starry-sky pattern.
Sporadic Burkitt lymphoma. This case of Burkitt lymphoma involved the nasopharynx. A starry-sky pattern is present and the lymphoma cells are monomorphic and of intermediate size.
Sporadic Burkitt lymphoma. Virtually all of the lymphoma cells are proliferating, as shown by Ki-67 immunohistochemistry.
Sporadic Burkitt lymphoma. The lymphoma cells are monomorphic with numerous cytoplasmic vacuoles, as seen on this cytospin preparation of a fine-needle aspirate stained with Giemsa.
Immunodeficiency-associated Burkitt lymphoma. This Burkitt lymphoma involving cervical lymph nodes developed in a man with HIV infection. The neoplasm has a prominent starry-sky pattern.
Immunodeficiency-associated Burkitt lymphoma. High-magnification view of Burkitt lymphoma involving cervical lymph nodes in a man with HIV infection. The lymphoma cells are monomorphic and of intermediate size, with multiple small nucleoli.
Immunodeficiency-associated Burkitt lymphoma. In this case of HIV-associated Burkitt lymphoma, virtually all of the cells were positive for EBV infection (in situ hybridization for EBV-encoded small RNA [EBER] with eosin counterstain).
Endemic Burkitt lymphoma. An African boy with Burkitt lymphoma involving his maxillary region.

Q: Microscopically, Diffuse Large B-Cell Lymphoma is characterized by a diffuse architectural pattern composed of large cells, most often [...] or immunoblasts, with frequent mitotic figures.
Diffuse large B-cell lymphoma of the nasopharynx. Large centroblasts and some centrocytes replace normal tissue.
Diffuse large B-cell lymphoma of the tonsil. Oil magnification showing the centroblastic features of the lymphoma cells. Histiocytes and mitotic figures are also present in the field.
A: centroblasts
Back Extra: Diffuse Large B-Cell Lymphoma
- Clinical: Patients with Diffuse Large B-Cell Lymphoma (DLBCL) often present with a mass and site-specific symptoms, such as altered vision, sinus or nasal cavity obstruction, oropharyngeal ulcers, enlarged tonsils, or hoarseness.
- Micro: DLBCL is composed of centroblasts or, less often, immunoblasts arranged in a diffuse pattern. Mitotic figures are common, and coagulative necrosis may be present.
- Ancillary: Interphase cytogenetic testing is recommended to exclude DLBCL with MYC and BCL2 rearrangements. Ki-67 shows a high proliferation index (60-90%).
Reference Gallery:
Diffuse large B-cell lymphoma of the nasopharynx. The neoplasm diffusely replaces the mucosa. Normal epithelium is present at the top of the field.
Diffuse large B-cell lymphoma of the nasopharynx. Large centroblasts and some centrocytes replace normal tissue.
Diffuse large B-cell lymphoma of the nasopharynx. The neoplasm is strongly positive for CD20, supporting a B-cell lineage.
Diffuse large B-cell lymphoma of the tonsil. The neoplasm diffusely replaces the tonsillar parenchyma. Squamous epithelium from the surface of the tonsil is also present in the field.
Diffuse large B-cell lymphoma of the tonsil. Oil magnification showing the centroblastic features of the lymphoma cells. Histiocytes and mitotic figures are also present in the field.
Diffuse large B-cell lymphoma of the tonsil. The lymphoma cells are strongly positive for IRF4 (MUM1), and CD10 was negative (not shown), supporting a non–germinal-centre B-cell immunophenotype.

Q: In Diffuse Large B-Cell Lymphoma, a non-germinal center B-cell immunophenotype is typically supported by strong immunohistochemical positivity for [...] alongside negative CD10 staining.
Diffuse large B-cell lymphoma of the tonsil. The lymphoma cells are strongly positive for IRF4 (MUM1), and CD10 was negative (not shown), supporting a non–germinal-centre B-cell immunophenotype.
A: IRF4 (MUM1)
Back Extra: Diffuse Large B-Cell Lymphoma
- Clinical: Patients with Diffuse Large B-Cell Lymphoma (DLBCL) often present with a mass and site-specific symptoms, such as altered vision, sinus or nasal cavity obstruction, oropharyngeal ulcers, enlarged tonsils, or hoarseness.
- Micro: DLBCL is composed of centroblasts or, less often, immunoblasts arranged in a diffuse pattern. Mitotic figures are common, and coagulative necrosis may be present.
- Ancillary: Interphase cytogenetic testing is recommended to exclude DLBCL with MYC and BCL2 rearrangements. Ki-67 shows a high proliferation index (60-90%).
Reference Gallery:
Diffuse large B-cell lymphoma of the nasopharynx. The neoplasm diffusely replaces the mucosa. Normal epithelium is present at the top of the field.
Diffuse large B-cell lymphoma of the nasopharynx. Large centroblasts and some centrocytes replace normal tissue.
Diffuse large B-cell lymphoma of the nasopharynx. The neoplasm is strongly positive for CD20, supporting a B-cell lineage.
Diffuse large B-cell lymphoma of the tonsil. The neoplasm diffusely replaces the tonsillar parenchyma. Squamous epithelium from the surface of the tonsil is also present in the field.
Diffuse large B-cell lymphoma of the tonsil. Oil magnification showing the centroblastic features of the lymphoma cells. Histiocytes and mitotic figures are also present in the field.
Diffuse large B-cell lymphoma of the tonsil. The lymphoma cells are strongly positive for IRF4 (MUM1), and CD10 was negative (not shown), supporting a non–germinal-centre B-cell immunophenotype.

Q: To confirm a B-cell lineage, the neoplastic cells of Diffuse Large B-Cell Lymphoma typically show strong, diffuse immunohistochemical membrane staining for [...].
Diffuse large B-cell lymphoma of the nasopharynx. The neoplasm is strongly positive for CD20, supporting a B-cell lineage.
A: CD20
Back Extra: Diffuse Large B-Cell Lymphoma
- Clinical: Patients with Diffuse Large B-Cell Lymphoma (DLBCL) often present with a mass and site-specific symptoms, such as altered vision, sinus or nasal cavity obstruction, oropharyngeal ulcers, enlarged tonsils, or hoarseness.
- Micro: DLBCL is composed of centroblasts or, less often, immunoblasts arranged in a diffuse pattern. Mitotic figures are common, and coagulative necrosis may be present.
- Ancillary: Interphase cytogenetic testing is recommended to exclude DLBCL with MYC and BCL2 rearrangements. Ki-67 shows a high proliferation index (60-90%).
Reference Gallery:
Diffuse large B-cell lymphoma of the nasopharynx. The neoplasm diffusely replaces the mucosa. Normal epithelium is present at the top of the field.
Diffuse large B-cell lymphoma of the nasopharynx. Large centroblasts and some centrocytes replace normal tissue.
Diffuse large B-cell lymphoma of the nasopharynx. The neoplasm is strongly positive for CD20, supporting a B-cell lineage.
Diffuse large B-cell lymphoma of the tonsil. The neoplasm diffusely replaces the tonsillar parenchyma. Squamous epithelium from the surface of the tonsil is also present in the field.
Diffuse large B-cell lymphoma of the tonsil. Oil magnification showing the centroblastic features of the lymphoma cells. Histiocytes and mitotic figures are also present in the field.
Diffuse large B-cell lymphoma of the tonsil. The lymphoma cells are strongly positive for IRF4 (MUM1), and CD10 was negative (not shown), supporting a non–germinal-centre B-cell immunophenotype.

Q: Histologically, Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue is characterized by a background of small lymphoid cells and pale monocytoid B cells that frequently infiltrate surrounding glandular structures to form characteristic [...].
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, parotid gland. Lymphoepithelial lesions are infiltrated and surrounded by pale monocytoid B cells in a background of small lymphoid cells.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. There is a lymphoepithelial lesion and surrounding monocytoid B cells.
A: lymphoepithelial lesions
Q: Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
- Clinical: Most patients with [...] present with painless enlarging masses, and B symptoms are rare.
- Micro: [...] is characterized by small lymphocytes and marginal zone cells with pale cytoplasm and occasional large lymphoid cells.
- Ancillary: Genetic changes in [...] often result in NF-κB activation, and trisomy 3 and trisomy 18 are common in head and neck EMZLs.
Reference Gallery:
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, parotid gland. Low-power view typically shows a variegated appearance, with some reactive lymphoid follicles. Broad pale bands (often centred around ducts) are also seen.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, parotid gland. Lymphoepithelial lesions are infiltrated and surrounded by pale monocytoid B cells in a background of small lymphoid cells.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. There is a lymphoepithelial lesion and surrounding monocytoid B cells.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. There are many atypical plasma cells with cytoplasmic inclusions adjacent to a well-formed lymphoepithelial lesion.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. Numerous kappa light chain–positive plasma cells and plasmacytoid cells indicate prominent plasmacytic differentiation.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. Only rare cells are positive for lambda light chains.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, tongue. Much of the tissue is replaced by an interfollicular, vaguely nodular, and diffuse proliferation of marginal zone B cells. Residual reactive follicles are present at the right of the image.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, tongue. The marginal zone B cells are diffusely positive for IRTA1.
A: Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue

Q: When Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue exhibits prominent plasmacytic differentiation, ancillary studies (such as in situ hybridization) will typically demonstrate [...] to confirm monoclonality.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. Numerous kappa light chain–positive plasma cells and plasmacytoid cells indicate prominent plasmacytic differentiation.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. Only rare cells are positive for lambda light chains.
A: light chain restriction
Q: Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
- Clinical: Most patients with [...] present with painless enlarging masses, and B symptoms are rare.
- Micro: [...] is characterized by small lymphocytes and marginal zone cells with pale cytoplasm and occasional large lymphoid cells.
- Ancillary: Genetic changes in [...] often result in NF-κB activation, and trisomy 3 and trisomy 18 are common in head and neck EMZLs.
Reference Gallery:
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, parotid gland. Low-power view typically shows a variegated appearance, with some reactive lymphoid follicles. Broad pale bands (often centred around ducts) are also seen.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, parotid gland. Lymphoepithelial lesions are infiltrated and surrounded by pale monocytoid B cells in a background of small lymphoid cells.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. There is a lymphoepithelial lesion and surrounding monocytoid B cells.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. There are many atypical plasma cells with cytoplasmic inclusions adjacent to a well-formed lymphoepithelial lesion.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. Numerous kappa light chain–positive plasma cells and plasmacytoid cells indicate prominent plasmacytic differentiation.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. Only rare cells are positive for lambda light chains.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, tongue. Much of the tissue is replaced by an interfollicular, vaguely nodular, and diffuse proliferation of marginal zone B cells. Residual reactive follicles are present at the right of the image.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, tongue. The marginal zone B cells are diffusely positive for IRTA1.
A: Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue

Q: In Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, the interfollicular and vaguely nodular proliferations of neoplastic marginal zone B cells characteristically show diffuse immunohistochemical positivity for [...].
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, tongue. Much of the tissue is replaced by an interfollicular, vaguely nodular, and diffuse proliferation of marginal zone B cells. Residual reactive follicles are present at the right of the image.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, tongue. The marginal zone B cells are diffusely positive for IRTA1.
A: IRTA1
Q: Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
- Clinical: Most patients with [...] present with painless enlarging masses, and B symptoms are rare.
- Micro: [...] is characterized by small lymphocytes and marginal zone cells with pale cytoplasm and occasional large lymphoid cells.
- Ancillary: Genetic changes in [...] often result in NF-κB activation, and trisomy 3 and trisomy 18 are common in head and neck EMZLs.
Reference Gallery:
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, parotid gland. Low-power view typically shows a variegated appearance, with some reactive lymphoid follicles. Broad pale bands (often centred around ducts) are also seen.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, parotid gland. Lymphoepithelial lesions are infiltrated and surrounded by pale monocytoid B cells in a background of small lymphoid cells.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. There is a lymphoepithelial lesion and surrounding monocytoid B cells.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. There are many atypical plasma cells with cytoplasmic inclusions adjacent to a well-formed lymphoepithelial lesion.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. Numerous kappa light chain–positive plasma cells and plasmacytoid cells indicate prominent plasmacytic differentiation.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, submandibular gland. Only rare cells are positive for lambda light chains.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, tongue. Much of the tissue is replaced by an interfollicular, vaguely nodular, and diffuse proliferation of marginal zone B cells. Residual reactive follicles are present at the right of the image.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, tongue. The marginal zone B cells are diffusely positive for IRTA1.
A: Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue

Q: Histologically, typical cases of Follicular Lymphoma feature numerous crowded neoplastic follicles that characteristically lack polarization and a [...] pattern.
Classic follicular lymphoma (grade 1/2). The neoplastic follicles lack polarization and a starry-sky pattern. They are mainly composed of centrocytes with a few interspersed centroblasts.
Follicular lymphoma of the tonsil. The tonsillar parenchyma is replaced by abnormal follicles with poorly defined mantles and monotonous-appearing germinal centres lacking tingible-body macrophages.
A: starry-sky
Back Extra: Follicular Lymphoma
- Clinical: Most patients with follicular lymphoma present with painless enlarging lymph nodes or masses, predominantly affecting adults with a median age of 65 years.
- Micro: Typical follicular lymphoma cases show numerous and crowded follicles consisting of centrocytes and centroblasts, lacking a starry-sky pattern and polarization.
- Ancillary: Follicular lymphoma is positive for CD20, BCL2, and the t(14;18)(q32;q21) BCL2 rearrangement, which is present in 85% of cases.
Reference Gallery:
Classic follicular lymphoma (grade 1/2). The neoplastic follicles lack polarization and a starry-sky pattern. They are mainly composed of centrocytes with a few interspersed centroblasts.
Classic follicular lymphoma (grade 1/2). The neoplastic cells are uniformly positive for BCL2.
Follicular lymphoma of the tonsil. The tonsillar parenchyma is replaced by abnormal follicles with poorly defined mantles and monotonous-appearing germinal centres lacking tingible-body macrophages.
Submandibular gland follicular lymphoma, grade 3A. In the submandibular glands, there are crowded large follicles with inconspicuous mantles.
Submandibular gland follicular lymphoma, grade 3A. The follicles comprise significant numbers of centroblasts mixed with centrocytes. Tingible-body macrophages are lacking.
Follicular large B-cell lymphoma (follicular lymphoma, grade 3B). Note the exclusive follicular growth pattern.
Follicular large B-cell lymphoma (follicular lymphoma, grade 3B). There is some variation in the size of the blasts; however, no typical centrocytes are present.

Q: Follicular Lymphoma strongly expresses BCL2 protein due to the [...] translocation, which is present in approximately 85% of cases.
Classic follicular lymphoma (grade 1/2). The neoplastic cells are uniformly positive for BCL2.
A: t(14;18)
Back Extra: Follicular Lymphoma
- Clinical: Most patients with follicular lymphoma present with painless enlarging lymph nodes or masses, predominantly affecting adults with a median age of 65 years.
- Micro: Typical follicular lymphoma cases show numerous and crowded follicles consisting of centrocytes and centroblasts, lacking a starry-sky pattern and polarization.
- Ancillary: Follicular lymphoma is positive for CD20, BCL2, and the t(14;18)(q32;q21) BCL2 rearrangement, which is present in 85% of cases.
Reference Gallery:
Classic follicular lymphoma (grade 1/2). The neoplastic follicles lack polarization and a starry-sky pattern. They are mainly composed of centrocytes with a few interspersed centroblasts.
Classic follicular lymphoma (grade 1/2). The neoplastic cells are uniformly positive for BCL2.
Follicular lymphoma of the tonsil. The tonsillar parenchyma is replaced by abnormal follicles with poorly defined mantles and monotonous-appearing germinal centres lacking tingible-body macrophages.
Submandibular gland follicular lymphoma, grade 3A. In the submandibular glands, there are crowded large follicles with inconspicuous mantles.
Submandibular gland follicular lymphoma, grade 3A. The follicles comprise significant numbers of centroblasts mixed with centrocytes. Tingible-body macrophages are lacking.
Follicular large B-cell lymphoma (follicular lymphoma, grade 3B). Note the exclusive follicular growth pattern.
Follicular large B-cell lymphoma (follicular lymphoma, grade 3B). There is some variation in the size of the blasts; however, no typical centrocytes are present.

Q: The crowded neoplastic follicles in classic grade 1/2 Follicular Lymphoma are predominantly composed of small to medium cleaved cells known as [...], interspersed with a variable number of larger centroblasts.
Classic follicular lymphoma (grade 1/2). The neoplastic follicles lack polarization and a starry-sky pattern. They are mainly composed of centrocytes with a few interspersed centroblasts.
Submandibular gland follicular lymphoma, grade 3A. The follicles comprise significant numbers of centroblasts mixed with centrocytes. Tingible-body macrophages are lacking.
A: centrocytes
Back Extra: Follicular Lymphoma
- Clinical: Most patients with follicular lymphoma present with painless enlarging lymph nodes or masses, predominantly affecting adults with a median age of 65 years.
- Micro: Typical follicular lymphoma cases show numerous and crowded follicles consisting of centrocytes and centroblasts, lacking a starry-sky pattern and polarization.
- Ancillary: Follicular lymphoma is positive for CD20, BCL2, and the t(14;18)(q32;q21) BCL2 rearrangement, which is present in 85% of cases.
Reference Gallery:
Classic follicular lymphoma (grade 1/2). The neoplastic follicles lack polarization and a starry-sky pattern. They are mainly composed of centrocytes with a few interspersed centroblasts.
Classic follicular lymphoma (grade 1/2). The neoplastic cells are uniformly positive for BCL2.
Follicular lymphoma of the tonsil. The tonsillar parenchyma is replaced by abnormal follicles with poorly defined mantles and monotonous-appearing germinal centres lacking tingible-body macrophages.
Submandibular gland follicular lymphoma, grade 3A. In the submandibular glands, there are crowded large follicles with inconspicuous mantles.
Submandibular gland follicular lymphoma, grade 3A. The follicles comprise significant numbers of centroblasts mixed with centrocytes. Tingible-body macrophages are lacking.
Follicular large B-cell lymphoma (follicular lymphoma, grade 3B). Note the exclusive follicular growth pattern.
Follicular large B-cell lymphoma (follicular lymphoma, grade 3B). There is some variation in the size of the blasts; however, no typical centrocytes are present.

Q: Morphologically, Large B-cell lymphoma with IRF4 rearrangement exhibits large, expansile follicles devoid of mantle zones and is characterized by [...] cytology.
Large B-cell lymphoma with IRF4 rearrangement. This example shows follicular growth with closely packed expansile follicles devoid of mantles.
Large B-cell lymphoma with IRF4 rearrangement. High-power view showing centroblastic cytology.
A: centroblastic
Back Extra: Large B-cell lymphoma with IRF4 rearrangement
- Clinical: Most patients present with localized lymph node or tonsillar enlargement (stage I/II) in the head and neck region. Median age at presentation is in the second decade of life, and it is more frequently encountered in patients aged < 18 years.
- Micro: LBCL IRF4+ may present with a follicular, follicular and diffuse, or entirely diffuse growth pattern. Neoplastic follicles are large, expansile, and devoid of mantle zones, with centroblastic morphology.
- Ancillary: Conventional cytogenetic analysis shows t(6;14)(p25.3;q32) (IGH::IRF4) or IGK/IGL partners. IRF4 rearrangements can be identified by FISH in most cases.
Reference Gallery:
Large B-cell lymphoma with IRF4 rearrangement. This lymphoma shows a partly follicular and partly diffuse growth pattern.
Large B-cell lymphoma with IRF4 rearrangement. This example shows follicular growth with closely packed expansile follicles devoid of mantles.
Large B-cell lymphoma with IRF4 rearrangement. High-power view showing centroblastic cytology.
Large B-cell lymphoma with IRF4 rearrangement. There is strong BCL6 expression.
Large B-cell lymphoma with IRF4 rearrangement. There is strong, uniform IRF4 (MUM1) expression.

Q: The defining diagnostic feature of Large B-cell lymphoma with IRF4 rearrangement is strong and uniform immunohistochemical expression of [...], driven by an underlying translocation.
Large B-cell lymphoma with IRF4 rearrangement. There is strong, uniform IRF4 (MUM1) expression.
A: IRF4 (MUM1)
Back Extra: Large B-cell lymphoma with IRF4 rearrangement
- Clinical: Most patients present with localized lymph node or tonsillar enlargement (stage I/II) in the head and neck region. Median age at presentation is in the second decade of life, and it is more frequently encountered in patients aged < 18 years.
- Micro: LBCL IRF4+ may present with a follicular, follicular and diffuse, or entirely diffuse growth pattern. Neoplastic follicles are large, expansile, and devoid of mantle zones, with centroblastic morphology.
- Ancillary: Conventional cytogenetic analysis shows t(6;14)(p25.3;q32) (IGH::IRF4) or IGK/IGL partners. IRF4 rearrangements can be identified by FISH in most cases.
Reference Gallery:
Large B-cell lymphoma with IRF4 rearrangement. This lymphoma shows a partly follicular and partly diffuse growth pattern.
Large B-cell lymphoma with IRF4 rearrangement. This example shows follicular growth with closely packed expansile follicles devoid of mantles.
Large B-cell lymphoma with IRF4 rearrangement. High-power view showing centroblastic cytology.
Large B-cell lymphoma with IRF4 rearrangement. There is strong BCL6 expression.
Large B-cell lymphoma with IRF4 rearrangement. There is strong, uniform IRF4 (MUM1) expression.

Q: In addition to strong MUM1 positivity, Large B-cell lymphoma with IRF4 rearrangement classically shows strong immunohistochemical expression of the germinal center marker [...].
Large B-cell lymphoma with IRF4 rearrangement. There is strong BCL6 expression.
A: BCL6
Back Extra: Large B-cell lymphoma with IRF4 rearrangement
- Clinical: Most patients present with localized lymph node or tonsillar enlargement (stage I/II) in the head and neck region. Median age at presentation is in the second decade of life, and it is more frequently encountered in patients aged < 18 years.
- Micro: LBCL IRF4+ may present with a follicular, follicular and diffuse, or entirely diffuse growth pattern. Neoplastic follicles are large, expansile, and devoid of mantle zones, with centroblastic morphology.
- Ancillary: Conventional cytogenetic analysis shows t(6;14)(p25.3;q32) (IGH::IRF4) or IGK/IGL partners. IRF4 rearrangements can be identified by FISH in most cases.
Reference Gallery:
Large B-cell lymphoma with IRF4 rearrangement. This lymphoma shows a partly follicular and partly diffuse growth pattern.
Large B-cell lymphoma with IRF4 rearrangement. This example shows follicular growth with closely packed expansile follicles devoid of mantles.
Large B-cell lymphoma with IRF4 rearrangement. High-power view showing centroblastic cytology.
Large B-cell lymphoma with IRF4 rearrangement. There is strong BCL6 expression.
Large B-cell lymphoma with IRF4 rearrangement. There is strong, uniform IRF4 (MUM1) expression.

Q: In Mantle Cell Lymphoma, the neoplastic cells characteristically express CD5 and overexpress [...] on immunohistochemistry, which correlates with the IGH::CCND1 rearrangement.
Mantle cell lymphoma involving tonsil. Neoplastic cells are small to medium-sized and have round to irregular nuclei, coarse chromatin, inconspicuous nucleoli, and scant cytoplasm. Mitotic figures are readily identified.
Mantle cell lymphoma involving tonsil. Immunohistochemical analysis shows that the neoplastic cells are positive for cyclin D1.
A: cyclin D1
Back Extra: Mantle Cell Lymphoma
- Clinical: Mantle cell lymphoma commonly presents in older adults with a median age in the seventh decade of life and a male predominance (M:F ratio 2–3:1).
- Micro: The lymphoma cells are uniform and small with irregular nuclear contours, often forming a diffuse or vaguely nodular pattern.
- Ancillary: Mantle cell lymphoma is characterized by the presence of CD5 and cyclin D1 positivity on immunohistochemistry, and the presence of the IGH::CCND1 rearrangement.
Reference Gallery:
Mantle cell lymphoma involving tonsil. The lymphoma has a nodular pattern, mimicking follicular lymphoma. Note the intact but compressed crypts lined by squamous epithelium.
Mantle cell lymphoma involving tonsil. Neoplastic cells are small to medium-sized and have round to irregular nuclei, coarse chromatin, inconspicuous nucleoli, and scant cytoplasm. Mitotic figures are readily identified.
Mantle cell lymphoma involving tonsil. The nodules are occupied by densely packed CD20+ B cells.
Mantle cell lymphoma involving tonsil. Immunohistochemical analysis shows that the neoplastic cells are positive for BCL2.
Mantle cell lymphoma involving tonsil. Immunohistochemical analysis shows that the neoplastic cells are positive for cyclin D1.
Mantle cell lymphoma involving tonsil. Immunohistochemical analysis shows that the neoplastic cells are negative for BCL6.

Q: A lymphoid neoplasm demonstrating a diffuse or vaguely nodular pattern composed of uniform, small-to-medium B cells with irregular nuclear contours and coarse chromatin is characteristic of [...].
Mantle cell lymphoma involving tonsil. The lymphoma has a nodular pattern, mimicking follicular lymphoma. Note the intact but compressed crypts lined by squamous epithelium.
Mantle cell lymphoma involving tonsil. Neoplastic cells are small to medium-sized and have round to irregular nuclei, coarse chromatin, inconspicuous nucleoli, and scant cytoplasm. Mitotic figures are readily identified.
A: Mantle Cell Lymphoma
Back Extra: Mantle Cell Lymphoma
- Clinical: Mantle cell lymphoma commonly presents in older adults with a median age in the seventh decade of life and a male predominance (M:F ratio 2–3:1).
- Micro: The lymphoma cells are uniform and small with irregular nuclear contours, often forming a diffuse or vaguely nodular pattern.
- Ancillary: Mantle cell lymphoma is characterized by the presence of CD5 and cyclin D1 positivity on immunohistochemistry, and the presence of the IGH::CCND1 rearrangement.
Reference Gallery:
Mantle cell lymphoma involving tonsil. The lymphoma has a nodular pattern, mimicking follicular lymphoma. Note the intact but compressed crypts lined by squamous epithelium.
Mantle cell lymphoma involving tonsil. Neoplastic cells are small to medium-sized and have round to irregular nuclei, coarse chromatin, inconspicuous nucleoli, and scant cytoplasm. Mitotic figures are readily identified.
Mantle cell lymphoma involving tonsil. The nodules are occupied by densely packed CD20+ B cells.
Mantle cell lymphoma involving tonsil. Immunohistochemical analysis shows that the neoplastic cells are positive for BCL2.
Mantle cell lymphoma involving tonsil. Immunohistochemical analysis shows that the neoplastic cells are positive for cyclin D1.
Mantle cell lymphoma involving tonsil. Immunohistochemical analysis shows that the neoplastic cells are negative for BCL6.

Q: In Paediatric-type Follicular Lymphoma, the lymph node architecture is typically replaced by large, expansile, and often serpiginous follicles that characteristically retain a prominent [...] pattern.
Paediatric-type follicular lymphoma. The atypical follicles are large and expanded, often serpiginous and with irregular contours. A starry-sky pattern is often preserved.
A: starry-sky
Back Extra: Paediatric-type Follicular Lymphoma
- Clinical: Patients with paediatric-type follicular lymphoma (PTFL) typically present with isolated, asymptomatic lymphadenopathy, and disseminated disease excludes the diagnosis of PTFL.
- Micro: The lymph node architecture is replaced by large, expansile follicles with a prominent starry-sky pattern and may be composed of intermediate-sized cells with blastoid features and multiple nucleoli.
- Ancillary: Immunophenotyping shows a monotypic B-cell population positive for CD10 and negative for CD5. BCL2 is negative or weakly and variably positive in 40–50% of cases.
Reference Gallery:
Paediatric-type follicular lymphoma. The atypical follicles are large and expanded, often serpiginous and with irregular contours. A starry-sky pattern is often preserved.
Paediatric-type follicular lymphoma. The neoplastic follicles are negative for BCL2.

Q: Unlike the classic adult variant, the neoplastic follicles in Paediatric-type Follicular Lymphoma are characteristically negative or only weakly and variably positive for the anti-apoptotic marker [...].
Paediatric-type follicular lymphoma. The neoplastic follicles are negative for BCL2.
A: BCL2
Back Extra: Paediatric-type Follicular Lymphoma
- Clinical: Patients with paediatric-type follicular lymphoma (PTFL) typically present with isolated, asymptomatic lymphadenopathy, and disseminated disease excludes the diagnosis of PTFL.
- Micro: The lymph node architecture is replaced by large, expansile follicles with a prominent starry-sky pattern and may be composed of intermediate-sized cells with blastoid features and multiple nucleoli.
- Ancillary: Immunophenotyping shows a monotypic B-cell population positive for CD10 and negative for CD5. BCL2 is negative or weakly and variably positive in 40–50% of cases.
Reference Gallery:
Paediatric-type follicular lymphoma. The atypical follicles are large and expanded, often serpiginous and with irregular contours. A starry-sky pattern is often preserved.
Paediatric-type follicular lymphoma. The neoplastic follicles are negative for BCL2.

Q: Morphologically, Plasmablastic Lymphoma presents as diffuse sheets of large cells resembling immunoblasts with frequent mitoses and tingible body macrophages, creating a characteristic [...] pattern.
Plasmablastic lymphoma. Immunoblastic morphology.
Plasmablastic lymphoma. Starry-sky pattern.
A: starry-sky
Back Extra: Plasmablastic Lymphoma
- Clinical: A tumour mass in the oral cavity is the most common presentation, with 75% of HIV-positive patients showing disseminated disease.
- Micro: Diffuse sheets of large cells resembling immunoblasts, often with a starry-sky pattern and high proliferative index.
- Ancillary: Neoplastic cells are typically negative for CD20 and PAX5 but positive for CD38, CD138, and IRF4 (MUM1).
Reference Gallery:
Plasmablastic lymphoma. Immunoblastic morphology.
Plasmablastic lymphoma. Plasmacytic features.
Plasmablastic lymphoma. Starry-sky pattern.
Plasmablastic lymphoma. The neoplastic cells are negative for CD20.
Plasmablastic lymphoma. Neoplastic cells strongly express the plasmacellular differentiation marker IRF4 (MUM1).
Plasmablastic lymphoma. Ki-67 immunostain shows a proliferation rate of > 95%.
Plasmablastic lymphoma. Neoplastic cells express EBV-encoded small RNA (EBER).
Plasmablastic lymphoma. Neoplastic cells express the plasmacellular differentiation marker CD38.

Q: Ancillary testing in Plasmablastic Lymphoma typically demonstrates a loss of mature B-cell markers such as [...] and PAX5, while remaining strongly positive for plasma cell markers like CD38, CD138, and IRF4 (MUM1).
Plasmablastic lymphoma. The neoplastic cells are negative for CD20.
Plasmablastic lymphoma. Neoplastic cells strongly express the plasmacellular differentiation marker IRF4 (MUM1).
Plasmablastic lymphoma. Neoplastic cells express the plasmacellular differentiation marker CD38.
A: CD20
Back Extra: Plasmablastic Lymphoma
- Clinical: A tumour mass in the oral cavity is the most common presentation, with 75% of HIV-positive patients showing disseminated disease.
- Micro: Diffuse sheets of large cells resembling immunoblasts, often with a starry-sky pattern and high proliferative index.
- Ancillary: Neoplastic cells are typically negative for CD20 and PAX5 but positive for CD38, CD138, and IRF4 (MUM1).
Reference Gallery:
Plasmablastic lymphoma. Immunoblastic morphology.
Plasmablastic lymphoma. Plasmacytic features.
Plasmablastic lymphoma. Starry-sky pattern.
Plasmablastic lymphoma. The neoplastic cells are negative for CD20.
Plasmablastic lymphoma. Neoplastic cells strongly express the plasmacellular differentiation marker IRF4 (MUM1).
Plasmablastic lymphoma. Ki-67 immunostain shows a proliferation rate of > 95%.
Plasmablastic lymphoma. Neoplastic cells express EBV-encoded small RNA (EBER).
Plasmablastic lymphoma. Neoplastic cells express the plasmacellular differentiation marker CD38.

Q: Plasmablastic Lymphoma is an aggressive tumor (frequently presenting as an oral cavity mass in HIV-positive patients) that exhibits an extremely high [...] proliferation index, often > 95%.
Plasmablastic lymphoma. Ki-67 immunostain shows a proliferation rate of > 95%.
A: Ki-67
Back Extra: Plasmablastic Lymphoma
- Clinical: A tumour mass in the oral cavity is the most common presentation, with 75% of HIV-positive patients showing disseminated disease.
- Micro: Diffuse sheets of large cells resembling immunoblasts, often with a starry-sky pattern and high proliferative index.
- Ancillary: Neoplastic cells are typically negative for CD20 and PAX5 but positive for CD38, CD138, and IRF4 (MUM1).
Reference Gallery:
Plasmablastic lymphoma. Immunoblastic morphology.
Plasmablastic lymphoma. Plasmacytic features.
Plasmablastic lymphoma. Starry-sky pattern.
Plasmablastic lymphoma. The neoplastic cells are negative for CD20.
Plasmablastic lymphoma. Neoplastic cells strongly express the plasmacellular differentiation marker IRF4 (MUM1).
Plasmablastic lymphoma. Ki-67 immunostain shows a proliferation rate of > 95%.
Plasmablastic lymphoma. Neoplastic cells express EBV-encoded small RNA (EBER).
Plasmablastic lymphoma. Neoplastic cells express the plasmacellular differentiation marker CD38.

Q: Microscopic examination of Plasmacytoma shows a subepithelial infiltrate of monotonous neoplastic cells characterized by eccentric, [...] nuclei and occasional focal binucleation.
Plasmacytoma. There is a monotonous proliferation of plasmacytoid cells in this field, with focal binucleation.
Plasmacytoma. Oil immersion reveals the eccentric, clock-face nuclei and occasional nucleoli.
A: clock-face
Back Extra: Plasmacytoma
- Clinical: Patients with solitary extramedullary plasmacytoma (SEP) most often present with a soft tissue mass (80%), followed by airway obstruction (35%), epistaxis (35%), and local pain (20%).
- Micro: Microscopic examination shows a subepithelial diffuse infiltrate of neoplastic plasma cells with a scant vascularized stroma, occasional haemorrhagic areas, and focal binucleation.
- Ancillary: Immunohistochemistry is positive for CD138, CD79a, and CD38, and shows light chain restriction, typically for kappa light chains.
Reference Gallery:
Plasmacytoma. A polypoid mass mimicking sinonasal polyposis is identified in the nasal cavity by MRI.
Plasmacytoma. There is adenoid enlargement in this nasopharyngeal endoscopy of a patient with plasmacytoma.
Plasmacytoma. There is an intact epithelium overlying a monotonous proliferation of plasmacytoid-appearing cells.
Plasmacytoma. The neoplastic cells exhibit a strong and diffuse reaction for CD138 by immunohistochemistry.
Plasmacytoma. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CD79a by immunohistochemistry.
Plasmacytoma. This plasmacytoma shows light chain restriction with a strong and diffuse reaction for kappa light chains by in situ hybridization.
Plasmacytoma. In situ hybridization is negative for lambda light chains.
Plasmacytoma. There is a monotonous proliferation of plasmacytoid cells in this field, with focal binucleation.
Plasmacytoma. There are occasional intracytoplasmic inclusions.
Plasmacytoma. Oil immersion reveals the eccentric, clock-face nuclei and occasional nucleoli.
Plasmacytoma. There is a monotonous proliferation of plasmacytoid cells in the submucosa.

Q: The neoplastic cells in Plasmacytoma demonstrate monoclonality by exhibiting [...] (e.g., diffuse kappa-positivity and lambda-negativity) on in situ hybridization.
Plasmacytoma. This plasmacytoma shows light chain restriction with a strong and diffuse reaction for kappa light chains by in situ hybridization.
Plasmacytoma. In situ hybridization is negative for lambda light chains.
A: light chain restriction
Back Extra: Plasmacytoma
- Clinical: Patients with solitary extramedullary plasmacytoma (SEP) most often present with a soft tissue mass (80%), followed by airway obstruction (35%), epistaxis (35%), and local pain (20%).
- Micro: Microscopic examination shows a subepithelial diffuse infiltrate of neoplastic plasma cells with a scant vascularized stroma, occasional haemorrhagic areas, and focal binucleation.
- Ancillary: Immunohistochemistry is positive for CD138, CD79a, and CD38, and shows light chain restriction, typically for kappa light chains.
Reference Gallery:
Plasmacytoma. A polypoid mass mimicking sinonasal polyposis is identified in the nasal cavity by MRI.
Plasmacytoma. There is adenoid enlargement in this nasopharyngeal endoscopy of a patient with plasmacytoma.
Plasmacytoma. There is an intact epithelium overlying a monotonous proliferation of plasmacytoid-appearing cells.
Plasmacytoma. The neoplastic cells exhibit a strong and diffuse reaction for CD138 by immunohistochemistry.
Plasmacytoma. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CD79a by immunohistochemistry.
Plasmacytoma. This plasmacytoma shows light chain restriction with a strong and diffuse reaction for kappa light chains by in situ hybridization.
Plasmacytoma. In situ hybridization is negative for lambda light chains.
Plasmacytoma. There is a monotonous proliferation of plasmacytoid cells in this field, with focal binucleation.
Plasmacytoma. There are occasional intracytoplasmic inclusions.
Plasmacytoma. Oil immersion reveals the eccentric, clock-face nuclei and occasional nucleoli.
Plasmacytoma. There is a monotonous proliferation of plasmacytoid cells in the submucosa.

Q: Immunohistochemistry for a Plasmacytoma typically demonstrates strong and diffuse positivity for plasma cell markers, including CD38 and [...].
Plasmacytoma. The neoplastic cells exhibit a strong and diffuse reaction for CD138 by immunohistochemistry.
A: CD138
Back Extra: Plasmacytoma
- Clinical: Patients with solitary extramedullary plasmacytoma (SEP) most often present with a soft tissue mass (80%), followed by airway obstruction (35%), epistaxis (35%), and local pain (20%).
- Micro: Microscopic examination shows a subepithelial diffuse infiltrate of neoplastic plasma cells with a scant vascularized stroma, occasional haemorrhagic areas, and focal binucleation.
- Ancillary: Immunohistochemistry is positive for CD138, CD79a, and CD38, and shows light chain restriction, typically for kappa light chains.
Reference Gallery:
Plasmacytoma. A polypoid mass mimicking sinonasal polyposis is identified in the nasal cavity by MRI.
Plasmacytoma. There is adenoid enlargement in this nasopharyngeal endoscopy of a patient with plasmacytoma.
Plasmacytoma. There is an intact epithelium overlying a monotonous proliferation of plasmacytoid-appearing cells.
Plasmacytoma. The neoplastic cells exhibit a strong and diffuse reaction for CD138 by immunohistochemistry.
Plasmacytoma. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CD79a by immunohistochemistry.
Plasmacytoma. This plasmacytoma shows light chain restriction with a strong and diffuse reaction for kappa light chains by in situ hybridization.
Plasmacytoma. In situ hybridization is negative for lambda light chains.
Plasmacytoma. There is a monotonous proliferation of plasmacytoid cells in this field, with focal binucleation.
Plasmacytoma. There are occasional intracytoplasmic inclusions.
Plasmacytoma. Oil immersion reveals the eccentric, clock-face nuclei and occasional nucleoli.
Plasmacytoma. There is a monotonous proliferation of plasmacytoid cells in the submucosa.

Q: The histopathology of Erdheim-Chester Disease is characterized by an infiltrate of foamy histiocytes mixed with chronic inflammatory cells, marked fibrosis, and multinucleated [...] giant cells.
Erdheim–Chester disease. Higher-power view of a biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease, showing numerous foamy histiocytes of varying sizes and shapes.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome showing numerous Touton giant cells and foamy histiocytes in the dermis. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. A biopsy of the left maxillary sinus of a 69-year-old man, showing inflammation and fibrosis. This lesion had BRAF p.V600E mutations.
A: Touton
Back Extra: Erdheim-Chester Disease
- Clinical: Patients with Erdheim-Chester disease often present with lower-extremity bone pain and fatigue, and may have multisystem involvement affecting the cerebellum, pituitary, lungs, heart, urinary tract, and retroperitoneum.
- Micro: The characteristic histopathology of Erdheim-Chester disease includes foamy histiocytes with Touton giant cells, chronic inflammatory cells, and marked fibrosis.
- Ancillary: Immunohistochemical staining for CD163, CD68, and phosphorylated ERK is positive in Erdheim-Chester disease, while CD1a and CD207 (langerin) stains are consistently negative.
Reference Gallery:
Erdheim–Chester disease. Whole-body PET-CT (maximum intensity projection) showing involvement of the mandible and the long bones of the legs.
Erdheim–Chester disease. Xanthelasma-like lesions are commonly located on the inner canthus of the eyelids.
Erdheim–Chester disease. Biopsy of the left maxillary sinus of a 69-year-old man, showing strong CD163 positivity. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of the left maxillary sinus of a 69-year-old man, showing positive staining for phosphorylated ERK. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease.
Erdheim–Chester disease. Higher-power view of a biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease, showing numerous foamy histiocytes of varying sizes and shapes.
Erdheim–Chester disease. Biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease, showing strong staining for CD68.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome showing numerous Touton giant cells and foamy histiocytes in the dermis. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome, showing histiocytes at higher magnification. In Erdheim–Chester disease, the infiltrate extends deeper into the dermis than in regular xanthelasma and may also involve the orbicularis oculi muscle, if included in the biopsy. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome, showing strong staining for CD163. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Lack of CD1a staining in a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. A biopsy of the left maxillary sinus of a 69-year-old man, showing inflammation and fibrosis. This lesion had BRAF p.V600E mutations.

Q: A classic clinical and radiographic presentation of Erdheim-Chester Disease involves pain and symmetric involvement affecting the [...] of the lower extremities.
Erdheim–Chester disease. Whole-body PET-CT (maximum intensity projection) showing involvement of the mandible and the long bones of the legs.
A: long bones
Back Extra: Erdheim-Chester Disease
- Clinical: Patients with Erdheim-Chester disease often present with lower-extremity bone pain and fatigue, and may have multisystem involvement affecting the cerebellum, pituitary, lungs, heart, urinary tract, and retroperitoneum.
- Micro: The characteristic histopathology of Erdheim-Chester disease includes foamy histiocytes with Touton giant cells, chronic inflammatory cells, and marked fibrosis.
- Ancillary: Immunohistochemical staining for CD163, CD68, and phosphorylated ERK is positive in Erdheim-Chester disease, while CD1a and CD207 (langerin) stains are consistently negative.
Reference Gallery:
Erdheim–Chester disease. Whole-body PET-CT (maximum intensity projection) showing involvement of the mandible and the long bones of the legs.
Erdheim–Chester disease. Xanthelasma-like lesions are commonly located on the inner canthus of the eyelids.
Erdheim–Chester disease. Biopsy of the left maxillary sinus of a 69-year-old man, showing strong CD163 positivity. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of the left maxillary sinus of a 69-year-old man, showing positive staining for phosphorylated ERK. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease.
Erdheim–Chester disease. Higher-power view of a biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease, showing numerous foamy histiocytes of varying sizes and shapes.
Erdheim–Chester disease. Biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease, showing strong staining for CD68.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome showing numerous Touton giant cells and foamy histiocytes in the dermis. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome, showing histiocytes at higher magnification. In Erdheim–Chester disease, the infiltrate extends deeper into the dermis than in regular xanthelasma and may also involve the orbicularis oculi muscle, if included in the biopsy. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome, showing strong staining for CD163. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Lack of CD1a staining in a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. A biopsy of the left maxillary sinus of a 69-year-old man, showing inflammation and fibrosis. This lesion had BRAF p.V600E mutations.

Q: The histiocytes in Erdheim-Chester Disease are characteristically positive for macrophage markers like CD68 and CD163, but consistently negative for [...] and CD207 (langerin).
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome, showing strong staining for CD163. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Lack of CD1a staining in a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome. This lesion had BRAF p.V600E mutations.
A: CD1a
Back Extra: Erdheim-Chester Disease
- Clinical: Patients with Erdheim-Chester disease often present with lower-extremity bone pain and fatigue, and may have multisystem involvement affecting the cerebellum, pituitary, lungs, heart, urinary tract, and retroperitoneum.
- Micro: The characteristic histopathology of Erdheim-Chester disease includes foamy histiocytes with Touton giant cells, chronic inflammatory cells, and marked fibrosis.
- Ancillary: Immunohistochemical staining for CD163, CD68, and phosphorylated ERK is positive in Erdheim-Chester disease, while CD1a and CD207 (langerin) stains are consistently negative.
Reference Gallery:
Erdheim–Chester disease. Whole-body PET-CT (maximum intensity projection) showing involvement of the mandible and the long bones of the legs.
Erdheim–Chester disease. Xanthelasma-like lesions are commonly located on the inner canthus of the eyelids.
Erdheim–Chester disease. Biopsy of the left maxillary sinus of a 69-year-old man, showing strong CD163 positivity. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of the left maxillary sinus of a 69-year-old man, showing positive staining for phosphorylated ERK. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease.
Erdheim–Chester disease. Higher-power view of a biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease, showing numerous foamy histiocytes of varying sizes and shapes.
Erdheim–Chester disease. Biopsy of the nasal cavity of a 63-year-old man with known Erdheim–Chester disease, showing strong staining for CD68.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome showing numerous Touton giant cells and foamy histiocytes in the dermis. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome, showing histiocytes at higher magnification. In Erdheim–Chester disease, the infiltrate extends deeper into the dermis than in regular xanthelasma and may also involve the orbicularis oculi muscle, if included in the biopsy. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Biopsy of a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome, showing strong staining for CD163. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. Lack of CD1a staining in a xanthelasma from a 49-year-old normolipaemic woman with cerebellar syndrome. This lesion had BRAF p.V600E mutations.
Erdheim–Chester disease. A biopsy of the left maxillary sinus of a 69-year-old man, showing inflammation and fibrosis. This lesion had BRAF p.V600E mutations.

Q: Microscopically, the tumor cells of Follicular Dendritic Cell Sarcoma have pale eosinophilic cytoplasm with indistinct borders, imparting a characteristic [...] appearance with intermingled small lymphocytes.
Follicular dendritic cell sarcoma. There are plump spindly cells with indistinct borders, moderate eosinophilic cytoplasm, and ovoid nuclei with vesicular chromatin. There are a few intermixed lymphocytes. In this example there are frequent mitotic figures.
Follicular dendritic cell sarcoma of the tonsil. The plump spindly cells have indistinct cell borders, vesicular nuclei, and distinct nucleoli. There are many intermingled small lymphocytes.
A: syncytial
Back Extra: Follicular Dendritic Cell Sarcoma
- Clinical: Patients with nodal tumours typically present with slow-growing neck masses that may be asymptomatic or painful. In the Waldeyer ring, there may be intraoral swelling or dysphagia.
- Micro: The tumour cells have a moderate amount of pale eosinophilic cytoplasm and indistinct cell borders, imparting a syncytial appearance. The nuclei have vesicular or granular finely dispersed chromatin.
- Ancillary: Expression of a marker of FDCs, such as CD21, CD23, CD35, clusterin, and CXCL13, is essential for diagnosis. A broad immunohistochemical panel should be used.
Reference Gallery:
Follicular dendritic cell sarcoma. The nodal architecture is replaced by the follicular dendritic cell sarcoma infiltrate and shows the capsular reaction and a focus of necrosis (lower right).
Follicular dendritic cell sarcoma. There are plump spindly cells with indistinct borders, moderate eosinophilic cytoplasm, and ovoid nuclei with vesicular chromatin. There are a few intermixed lymphocytes. In this example there are frequent mitotic figures.
Follicular dendritic cell sarcoma. Positive membranous staining for CD21.
Follicular dendritic cell sarcoma. Positive membranous staining for CD35.
Follicular dendritic cell sarcoma. CXCL13, although not specific, shows cytoplasmic staining often with a Golgi/cytoplasmic dot-like staining pattern.
Follicular dendritic cell sarcoma. PDL1 staining (expression of the inhibitory immune receptor PD1 and its ligands PDL1 and PDL2 could be potential therapeutic targets).
Follicular dendritic cell sarcoma of the tonsil. The tumour (central field) forms an expansile, pushing growth in the tonsil. Ulceration is present at the left.
Follicular dendritic cell sarcoma of the tonsil. The plump spindly cells have indistinct cell borders, vesicular nuclei, and distinct nucleoli. There are many intermingled small lymphocytes.

Q: The immunohistochemical diagnosis of Follicular Dendritic Cell Sarcoma requires the expression of essential dendritic cell markers, most notably [...], alongside CD23 and clusterin.
Follicular dendritic cell sarcoma. Positive membranous staining for CD21.
Follicular dendritic cell sarcoma. Positive membranous staining for CD35.
A: CD21 and CD35
Back Extra: Follicular Dendritic Cell Sarcoma
- Clinical: Patients with nodal tumours typically present with slow-growing neck masses that may be asymptomatic or painful. In the Waldeyer ring, there may be intraoral swelling or dysphagia.
- Micro: The tumour cells have a moderate amount of pale eosinophilic cytoplasm and indistinct cell borders, imparting a syncytial appearance. The nuclei have vesicular or granular finely dispersed chromatin.
- Ancillary: Expression of a marker of FDCs, such as CD21, CD23, CD35, clusterin, and CXCL13, is essential for diagnosis. A broad immunohistochemical panel should be used.
Reference Gallery:
Follicular dendritic cell sarcoma. The nodal architecture is replaced by the follicular dendritic cell sarcoma infiltrate and shows the capsular reaction and a focus of necrosis (lower right).
Follicular dendritic cell sarcoma. There are plump spindly cells with indistinct borders, moderate eosinophilic cytoplasm, and ovoid nuclei with vesicular chromatin. There are a few intermixed lymphocytes. In this example there are frequent mitotic figures.
Follicular dendritic cell sarcoma. Positive membranous staining for CD21.
Follicular dendritic cell sarcoma. Positive membranous staining for CD35.
Follicular dendritic cell sarcoma. CXCL13, although not specific, shows cytoplasmic staining often with a Golgi/cytoplasmic dot-like staining pattern.
Follicular dendritic cell sarcoma. PDL1 staining (expression of the inhibitory immune receptor PD1 and its ligands PDL1 and PDL2 could be potential therapeutic targets).
Follicular dendritic cell sarcoma of the tonsil. The tumour (central field) forms an expansile, pushing growth in the tonsil. Ulceration is present at the left.
Follicular dendritic cell sarcoma of the tonsil. The plump spindly cells have indistinct cell borders, vesicular nuclei, and distinct nucleoli. There are many intermingled small lymphocytes.

Q: Classic histologic findings of Juvenile xanthogranuloma include a well-circumscribed dermal proliferation of histiocytes admixed with lymphocytes, eosinophils, and characteristic multinucleated [...] giant cells.
Juvenile xanthogranuloma. Classic morphology displaying small histiocytes with ovoid nuclei and pink cytoplasm admixed with xanthomatous cells and Touton giant cells.
A: Touton
Back Extra: Juvenile xanthogranuloma
- Clinical: Juvenile xanthogranuloma (JXG) is generally asymptomatic and evolves from a raised, pink to darker-brown lesion with progressive flattening. It is commonly found on the head and neck, upper trunk, and proximal extremities.
- Micro: JXGs are unencapsulated, well-circumscribed lesions in the papillary dermis, composed of histiocytes intermixed with lymphocytes, eosinophils, plasma cells, and Touton giant cells.
- Ancillary: Activating mutations in NRAS, KRAS, ARAF, and MAP2K1, as well as an RNF11::BRAF fusion, have been reported in systemic JXGs.
Reference Gallery:
Juvenile xanthogranuloma. Classic morphology displaying small histiocytes with ovoid nuclei and pink cytoplasm admixed with xanthomatous cells and Touton giant cells.
Juvenile xanthogranuloma family. In some early cases the classic morphology including xanthomatous cells and Touton giant cells is lacking, but there is a juvenile xanthogranuloma phenotype. The histiocytes infiltrate through the orbital muscle. This case harboured a CSF1R in-frame deletion.
Juvenile xanthogranuloma family. CD163 is diffusely expressed in an orbital soft tissue juvenile xanthogranuloma.
Juvenile xanthogranuloma family. Factor XIIIa is diffusely expressed in an orbital soft tissue juvenile xanthogranuloma.
Juvenile xanthogranuloma family. The histiocytes in the juvenile xanthogranuloma family of lesions have ample pink cytoplasm and bland, round to ovoid nuclei with variable mild nuclear indentation, without grooves and complex folding, distinguishing them from those in Langerhans cell histiocytosis.

Q: Immunohistochemical evaluation of Juvenile xanthogranuloma typically demonstrates diffuse expression of macrophage markers (e.g., CD163) as well as the dendritic cell marker [...].
Juvenile xanthogranuloma family. CD163 is diffusely expressed in an orbital soft tissue juvenile xanthogranuloma.
Juvenile xanthogranuloma family. Factor XIIIa is diffusely expressed in an orbital soft tissue juvenile xanthogranuloma.
A: Factor XIIIa
Back Extra: Juvenile xanthogranuloma
- Clinical: Juvenile xanthogranuloma (JXG) is generally asymptomatic and evolves from a raised, pink to darker-brown lesion with progressive flattening. It is commonly found on the head and neck, upper trunk, and proximal extremities.
- Micro: JXGs are unencapsulated, well-circumscribed lesions in the papillary dermis, composed of histiocytes intermixed with lymphocytes, eosinophils, plasma cells, and Touton giant cells.
- Ancillary: Activating mutations in NRAS, KRAS, ARAF, and MAP2K1, as well as an RNF11::BRAF fusion, have been reported in systemic JXGs.
Reference Gallery:
Juvenile xanthogranuloma. Classic morphology displaying small histiocytes with ovoid nuclei and pink cytoplasm admixed with xanthomatous cells and Touton giant cells.
Juvenile xanthogranuloma family. In some early cases the classic morphology including xanthomatous cells and Touton giant cells is lacking, but there is a juvenile xanthogranuloma phenotype. The histiocytes infiltrate through the orbital muscle. This case harboured a CSF1R in-frame deletion.
Juvenile xanthogranuloma family. CD163 is diffusely expressed in an orbital soft tissue juvenile xanthogranuloma.
Juvenile xanthogranuloma family. Factor XIIIa is diffusely expressed in an orbital soft tissue juvenile xanthogranuloma.
Juvenile xanthogranuloma family. The histiocytes in the juvenile xanthogranuloma family of lesions have ample pink cytoplasm and bland, round to ovoid nuclei with variable mild nuclear indentation, without grooves and complex folding, distinguishing them from those in Langerhans cell histiocytosis.

Q: The histiocytes in Juvenile xanthogranuloma have ample pink cytoplasm and bland nuclei with variable mild indentation, but uniquely lack the prominent nuclear grooves and complex folding that are characteristic of [...].
Juvenile xanthogranuloma family. The histiocytes in the juvenile xanthogranuloma family of lesions have ample pink cytoplasm and bland, round to ovoid nuclei with variable mild nuclear indentation, without grooves and complex folding, distinguishing them from those in Langerhans cell histiocytosis.
A: Langerhans cell histiocytosis
Back Extra: Juvenile xanthogranuloma
- Clinical: Juvenile xanthogranuloma (JXG) is generally asymptomatic and evolves from a raised, pink to darker-brown lesion with progressive flattening. It is commonly found on the head and neck, upper trunk, and proximal extremities.
- Micro: JXGs are unencapsulated, well-circumscribed lesions in the papillary dermis, composed of histiocytes intermixed with lymphocytes, eosinophils, plasma cells, and Touton giant cells.
- Ancillary: Activating mutations in NRAS, KRAS, ARAF, and MAP2K1, as well as an RNF11::BRAF fusion, have been reported in systemic JXGs.
Reference Gallery:
Juvenile xanthogranuloma. Classic morphology displaying small histiocytes with ovoid nuclei and pink cytoplasm admixed with xanthomatous cells and Touton giant cells.
Juvenile xanthogranuloma family. In some early cases the classic morphology including xanthomatous cells and Touton giant cells is lacking, but there is a juvenile xanthogranuloma phenotype. The histiocytes infiltrate through the orbital muscle. This case harboured a CSF1R in-frame deletion.
Juvenile xanthogranuloma family. CD163 is diffusely expressed in an orbital soft tissue juvenile xanthogranuloma.
Juvenile xanthogranuloma family. Factor XIIIa is diffusely expressed in an orbital soft tissue juvenile xanthogranuloma.
Juvenile xanthogranuloma family. The histiocytes in the juvenile xanthogranuloma family of lesions have ample pink cytoplasm and bland, round to ovoid nuclei with variable mild nuclear indentation, without grooves and complex folding, distinguishing them from those in Langerhans cell histiocytosis.

Q: Microscopically, the neoplastic cells in Langerhans Cell Histiocytosis are characterized by abundant eosinophilic cytoplasm and grooved, folded, or [...]-shaped nuclei, often in an inflammatory background rich in eosinophils.
Langerhans cell histiocytosis. The cells are bland with ample cytoplasm and characteristic grooved and folded nuclei with fine chromatin. Occasional mitoses can be found.
Langerhans cell histiocytosis. The Langerhans cells have ample cytoplasm surrounding coffee bean–shaped or cleaved nuclei. There are numerous eosinophils in the background.
A: coffee bean
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Unifocal LCH affects older children and adults, while multifocal and multisystem LCH affects young children and infants, respectively. Common manifestations include oral lesions and diabetes insipidus in hypothalamic-pituitary involvement.
- Micro: LCH cells are characterized by grooved, folded nuclei, fine chromatin, and a moderate amount of eosinophilic cytoplasm. They are often admixed with eosinophils, histiocytes, and lymphocytes.
- Ancillary: Over 85% of LCH cases have MAPK pathway gene mutations, commonly affecting BRAF, MAP2K1, or ARAF. BRAF p.V600E mutations are identifiable by a specific immunostain.
Reference Gallery:
Langerhans cell histiocytosis. In this ear canal polyp with an ulcerated surface, the submucosa is expanded with lesional cells.
Langerhans cell histiocytosis. The cells are bland with ample cytoplasm and characteristic grooved and folded nuclei with fine chromatin. Occasional mitoses can be found.
Langerhans cell histiocytosis. CD207 (langerin) staining is granular and cytoplasmic, and serves as a surrogate for cytoplasmic Birbeck granule detection.
Langerhans cell histiocytosis. The mutant-specific BRAF VE1 immunostain corresponds to BRAF p.V600E mutations when dark, granular staining is seen in the cytoplasm of lesional cells.
Langerhans cell histiocytosis. Lesional cell clusters are often admixed with inflammatory cells. Ulceration of the surface may introduce more neutrophils and haemorrhage.
Langerhans cell histiocytosis. Phosphorylated ERK expression is nuclear with variable cytoplasmic staining, corresponding to the upregulation of the ERK pathway. Staining in endothelial nuclei serves as an internal control.
Langerhans cell histiocytosis. The Langerhans cells have ample cytoplasm surrounding coffee bean–shaped or cleaved nuclei. There are numerous eosinophils in the background.

Q: In Langerhans Cell Histiocytosis, positive immunostaining for CD207 (langerin) highlights granular cytoplasmic positivity and serves as a surrogate marker for the presence of ultrastructural [...].
Langerhans cell histiocytosis. CD207 (langerin) staining is granular and cytoplasmic, and serves as a surrogate for cytoplasmic Birbeck granule detection.
A: Birbeck granules
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Unifocal LCH affects older children and adults, while multifocal and multisystem LCH affects young children and infants, respectively. Common manifestations include oral lesions and diabetes insipidus in hypothalamic-pituitary involvement.
- Micro: LCH cells are characterized by grooved, folded nuclei, fine chromatin, and a moderate amount of eosinophilic cytoplasm. They are often admixed with eosinophils, histiocytes, and lymphocytes.
- Ancillary: Over 85% of LCH cases have MAPK pathway gene mutations, commonly affecting BRAF, MAP2K1, or ARAF. BRAF p.V600E mutations are identifiable by a specific immunostain.
Reference Gallery:
Langerhans cell histiocytosis. In this ear canal polyp with an ulcerated surface, the submucosa is expanded with lesional cells.
Langerhans cell histiocytosis. The cells are bland with ample cytoplasm and characteristic grooved and folded nuclei with fine chromatin. Occasional mitoses can be found.
Langerhans cell histiocytosis. CD207 (langerin) staining is granular and cytoplasmic, and serves as a surrogate for cytoplasmic Birbeck granule detection.
Langerhans cell histiocytosis. The mutant-specific BRAF VE1 immunostain corresponds to BRAF p.V600E mutations when dark, granular staining is seen in the cytoplasm of lesional cells.
Langerhans cell histiocytosis. Lesional cell clusters are often admixed with inflammatory cells. Ulceration of the surface may introduce more neutrophils and haemorrhage.
Langerhans cell histiocytosis. Phosphorylated ERK expression is nuclear with variable cytoplasmic staining, corresponding to the upregulation of the ERK pathway. Staining in endothelial nuclei serves as an internal control.
Langerhans cell histiocytosis. The Langerhans cells have ample cytoplasm surrounding coffee bean–shaped or cleaved nuclei. There are numerous eosinophils in the background.

Q: Over 85% of Langerhans Cell Histiocytosis cases harbor mutations in the MAPK pathway, most commonly a p.V600E mutation in the [...] gene, which can be confirmed with a specific VE1 immunostain.
Langerhans cell histiocytosis. The mutant-specific BRAF VE1 immunostain corresponds to BRAF p.V600E mutations when dark, granular staining is seen in the cytoplasm of lesional cells.
A: BRAF
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Unifocal LCH affects older children and adults, while multifocal and multisystem LCH affects young children and infants, respectively. Common manifestations include oral lesions and diabetes insipidus in hypothalamic-pituitary involvement.
- Micro: LCH cells are characterized by grooved, folded nuclei, fine chromatin, and a moderate amount of eosinophilic cytoplasm. They are often admixed with eosinophils, histiocytes, and lymphocytes.
- Ancillary: Over 85% of LCH cases have MAPK pathway gene mutations, commonly affecting BRAF, MAP2K1, or ARAF. BRAF p.V600E mutations are identifiable by a specific immunostain.
Reference Gallery:
Langerhans cell histiocytosis. In this ear canal polyp with an ulcerated surface, the submucosa is expanded with lesional cells.
Langerhans cell histiocytosis. The cells are bland with ample cytoplasm and characteristic grooved and folded nuclei with fine chromatin. Occasional mitoses can be found.
Langerhans cell histiocytosis. CD207 (langerin) staining is granular and cytoplasmic, and serves as a surrogate for cytoplasmic Birbeck granule detection.
Langerhans cell histiocytosis. The mutant-specific BRAF VE1 immunostain corresponds to BRAF p.V600E mutations when dark, granular staining is seen in the cytoplasm of lesional cells.
Langerhans cell histiocytosis. Lesional cell clusters are often admixed with inflammatory cells. Ulceration of the surface may introduce more neutrophils and haemorrhage.
Langerhans cell histiocytosis. Phosphorylated ERK expression is nuclear with variable cytoplasmic staining, corresponding to the upregulation of the ERK pathway. Staining in endothelial nuclei serves as an internal control.
Langerhans cell histiocytosis. The Langerhans cells have ample cytoplasm surrounding coffee bean–shaped or cleaved nuclei. There are numerous eosinophils in the background.

Q: At high magnification, the hallmark histologic finding in Rosai-Dorfman Disease is the presence of intact lymphocytes within the cytoplasm of large histiocytes, a phenomenon known as [...].
Rosai–Dorfman disease involving a lymph node. At low magnification, the lymph node has a striated appearance due to distended pale sinuses and intervening darker cords of lymphocytes and plasma cells.
Rosai–Dorfman disease involving a lymph node. A large histiocyte with numerous intracytoplasmic lymphocytes (emperipolesis) is present in a distended sinus.
A: emperipolesis
Back Extra: Rosai-Dorfman Disease
- Clinical: Most patients present with painless, slow-growing lymphadenopathy or an extranodal mass; about one-third have B-type symptoms.
- Micro: Lymph nodes show expanded sinuses filled by large histiocytes with emperipolesis, hypochromatic nuclei, and a striated appearance at low power.
- Ancillary: Histiocytes are strongly positive for S100 and OCT2, and often have mutations in the MAPK/ERK pathway.
Reference Gallery:
Rosai–Dorfman disease involving a lymph node. At low magnification, the lymph node has a striated appearance due to distended pale sinuses and intervening darker cords of lymphocytes and plasma cells.
Rosai–Dorfman disease involving a lymph node. A large histiocyte with numerous intracytoplasmic lymphocytes (emperipolesis) is present in a distended sinus.
Rosai–Dorfman disease involving a lymph node. Numerous characteristic histiocytes are positive for S100. The reaction product also outlines unstained small lymphocytes within the histiocyte cytoplasm.
Rosai–Dorfman disease involving a lymph node. The histiocytes are positive for phosphorylated ERK, indicating that the MAPK/ERK pathway is activated, probably due to a mutated gene in the pathway.
Rosai–Dorfman disease involving the parotid gland. In this field, Rosai–Dorfman disease infiltrates and distorts the acinar tissue of the parotid gland. Although there are many characteristic histiocytes, emperipolesis is relatively minimal, which is common at extranodal sites of disease.

Q: The characteristic large histiocytes of Rosai-Dorfman Disease are classically strongly positive for the immunohistochemical marker [...], which neatly outlines the unstained engulfed lymphocytes.
Rosai–Dorfman disease involving a lymph node. Numerous characteristic histiocytes are positive for S100. The reaction product also outlines unstained small lymphocytes within the histiocyte cytoplasm.
A: S100
Back Extra: Rosai-Dorfman Disease
- Clinical: Most patients present with painless, slow-growing lymphadenopathy or an extranodal mass; about one-third have B-type symptoms.
- Micro: Lymph nodes show expanded sinuses filled by large histiocytes with emperipolesis, hypochromatic nuclei, and a striated appearance at low power.
- Ancillary: Histiocytes are strongly positive for S100 and OCT2, and often have mutations in the MAPK/ERK pathway.
Reference Gallery:
Rosai–Dorfman disease involving a lymph node. At low magnification, the lymph node has a striated appearance due to distended pale sinuses and intervening darker cords of lymphocytes and plasma cells.
Rosai–Dorfman disease involving a lymph node. A large histiocyte with numerous intracytoplasmic lymphocytes (emperipolesis) is present in a distended sinus.
Rosai–Dorfman disease involving a lymph node. Numerous characteristic histiocytes are positive for S100. The reaction product also outlines unstained small lymphocytes within the histiocyte cytoplasm.
Rosai–Dorfman disease involving a lymph node. The histiocytes are positive for phosphorylated ERK, indicating that the MAPK/ERK pathway is activated, probably due to a mutated gene in the pathway.
Rosai–Dorfman disease involving the parotid gland. In this field, Rosai–Dorfman disease infiltrates and distorts the acinar tissue of the parotid gland. Although there are many characteristic histiocytes, emperipolesis is relatively minimal, which is common at extranodal sites of disease.

Q: The molecular pathogenesis of Rosai-Dorfman Disease frequently involves activating mutations in the [...] signaling pathway, which can be demonstrated using immunohistochemistry for its phosphorylated kinase.
Rosai–Dorfman disease involving a lymph node. The histiocytes are positive for phosphorylated ERK, indicating that the MAPK/ERK pathway is activated, probably due to a mutated gene in the pathway.
A: MAPK/ERK
Back Extra: Rosai-Dorfman Disease
- Clinical: Most patients present with painless, slow-growing lymphadenopathy or an extranodal mass; about one-third have B-type symptoms.
- Micro: Lymph nodes show expanded sinuses filled by large histiocytes with emperipolesis, hypochromatic nuclei, and a striated appearance at low power.
- Ancillary: Histiocytes are strongly positive for S100 and OCT2, and often have mutations in the MAPK/ERK pathway.
Reference Gallery:
Rosai–Dorfman disease involving a lymph node. At low magnification, the lymph node has a striated appearance due to distended pale sinuses and intervening darker cords of lymphocytes and plasma cells.
Rosai–Dorfman disease involving a lymph node. A large histiocyte with numerous intracytoplasmic lymphocytes (emperipolesis) is present in a distended sinus.
Rosai–Dorfman disease involving a lymph node. Numerous characteristic histiocytes are positive for S100. The reaction product also outlines unstained small lymphocytes within the histiocyte cytoplasm.
Rosai–Dorfman disease involving a lymph node. The histiocytes are positive for phosphorylated ERK, indicating that the MAPK/ERK pathway is activated, probably due to a mutated gene in the pathway.
Rosai–Dorfman disease involving the parotid gland. In this field, Rosai–Dorfman disease infiltrates and distorts the acinar tissue of the parotid gland. Although there are many characteristic histiocytes, emperipolesis is relatively minimal, which is common at extranodal sites of disease.

Q: Classic Hodgkin Lymphoma is microscopically characterized by large, binucleated or multinucleated [...] cells scattered within a mixed inflammatory background.
Classic Hodgkin lymphoma, mixed cellularity. Normal nasopharyngeal tissue is replaced by a diffuse lymphoid proliferation with an inflammatory background and dispersed Hodgkin/Reed–Sternberg (HRS) cells.
Classic Hodgkin lymphoma, mixed cellularity. Diffuse inflammatory background with dispersed Hodgkin/Reed–Sternberg (HRS) cells.
A: Reed-Sternberg
Back Extra: Hodgkin Lymphoma
- Clinical: Hodgkin lymphoma typically involves the Waldeyer ring, including the nasopharynx and tonsils, and can present with local symptoms like difficulty swallowing or nasal obstruction.
- Micro: Classic Hodgkin lymphoma (CHL) is characterized by the presence of large, binucleated or multinucleated Hodgkin/Reed–Sternberg (HRS) cells in a mixed inflammatory background.
- Ancillary: HRS cells in CHL express CD30 and CD15, while lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) express CD20 and B-cell transcription factors.
Reference Gallery:
Classic Hodgkin lymphoma, mixed cellularity. MRI showing a mass limited to the nasopharynx.
Nodular lymphocyte-predominant Hodgkin lymphoma. Low-power view shows a vaguely nodular pattern in an intraparotid lymph node.
Nodular lymphocyte-predominant Hodgkin lymphoma. CD20+ lymphocyte-predominant cells are rosetted by CD20− cells in a nodular background rich in small B lymphocytes.
Nodular lymphocyte-predominant Hodgkin lymphoma. Lymphocyte-predominant cells are rosetted by PD1+ T follicular helper (TFH) cells.
Classic Hodgkin lymphoma, mixed cellularity. Normal nasopharyngeal tissue is replaced by a diffuse lymphoid proliferation with an inflammatory background and dispersed Hodgkin/Reed–Sternberg (HRS) cells.
Classic Hodgkin lymphoma, mixed cellularity. Diffuse inflammatory background with dispersed Hodgkin/Reed–Sternberg (HRS) cells.
Classic Hodgkin lymphoma, mixed cellularity. The Hodgkin/Reed–Sternberg (HRS) cells express CD30.
Nodular lymphocyte-predominant Hodgkin lymphoma. Nodular pattern with a predominance of small lymphocytes and scattered large atypical lymphocyte-predominant cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. OCT2 immunostaining highlights the nuclei of the lymphocyte-predominant cells in the nodular background.

Q: In Classic Hodgkin Lymphoma, the pathognomonic Hodgkin/Reed-Sternberg (HRS) cells characteristically express the immunomarkers CD15 and [...].
Classic Hodgkin lymphoma, mixed cellularity. The Hodgkin/Reed–Sternberg (HRS) cells express CD30.
A: CD30
Back Extra: Hodgkin Lymphoma
- Clinical: Hodgkin lymphoma typically involves the Waldeyer ring, including the nasopharynx and tonsils, and can present with local symptoms like difficulty swallowing or nasal obstruction.
- Micro: Classic Hodgkin lymphoma (CHL) is characterized by the presence of large, binucleated or multinucleated Hodgkin/Reed–Sternberg (HRS) cells in a mixed inflammatory background.
- Ancillary: HRS cells in CHL express CD30 and CD15, while lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) express CD20 and B-cell transcription factors.
Reference Gallery:
Classic Hodgkin lymphoma, mixed cellularity. MRI showing a mass limited to the nasopharynx.
Nodular lymphocyte-predominant Hodgkin lymphoma. Low-power view shows a vaguely nodular pattern in an intraparotid lymph node.
Nodular lymphocyte-predominant Hodgkin lymphoma. CD20+ lymphocyte-predominant cells are rosetted by CD20− cells in a nodular background rich in small B lymphocytes.
Nodular lymphocyte-predominant Hodgkin lymphoma. Lymphocyte-predominant cells are rosetted by PD1+ T follicular helper (TFH) cells.
Classic Hodgkin lymphoma, mixed cellularity. Normal nasopharyngeal tissue is replaced by a diffuse lymphoid proliferation with an inflammatory background and dispersed Hodgkin/Reed–Sternberg (HRS) cells.
Classic Hodgkin lymphoma, mixed cellularity. Diffuse inflammatory background with dispersed Hodgkin/Reed–Sternberg (HRS) cells.
Classic Hodgkin lymphoma, mixed cellularity. The Hodgkin/Reed–Sternberg (HRS) cells express CD30.
Nodular lymphocyte-predominant Hodgkin lymphoma. Nodular pattern with a predominance of small lymphocytes and scattered large atypical lymphocyte-predominant cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. OCT2 immunostaining highlights the nuclei of the lymphocyte-predominant cells in the nodular background.

Q: In Nodular Lymphocyte-Predominant Hodgkin Lymphoma, the large atypical lymphocyte-predominant (LP) cells distinctively express the B-cell marker [...].
Nodular lymphocyte-predominant Hodgkin lymphoma. CD20+ lymphocyte-predominant cells are rosetted by CD20− cells in a nodular background rich in small B lymphocytes.
A: CD20
Back Extra: Hodgkin Lymphoma
- Clinical: Hodgkin lymphoma typically involves the Waldeyer ring, including the nasopharynx and tonsils, and can present with local symptoms like difficulty swallowing or nasal obstruction.
- Micro: Classic Hodgkin lymphoma (CHL) is characterized by the presence of large, binucleated or multinucleated Hodgkin/Reed–Sternberg (HRS) cells in a mixed inflammatory background.
- Ancillary: HRS cells in CHL express CD30 and CD15, while lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) express CD20 and B-cell transcription factors.
Reference Gallery:
Classic Hodgkin lymphoma, mixed cellularity. MRI showing a mass limited to the nasopharynx.
Nodular lymphocyte-predominant Hodgkin lymphoma. Low-power view shows a vaguely nodular pattern in an intraparotid lymph node.
Nodular lymphocyte-predominant Hodgkin lymphoma. CD20+ lymphocyte-predominant cells are rosetted by CD20− cells in a nodular background rich in small B lymphocytes.
Nodular lymphocyte-predominant Hodgkin lymphoma. Lymphocyte-predominant cells are rosetted by PD1+ T follicular helper (TFH) cells.
Classic Hodgkin lymphoma, mixed cellularity. Normal nasopharyngeal tissue is replaced by a diffuse lymphoid proliferation with an inflammatory background and dispersed Hodgkin/Reed–Sternberg (HRS) cells.
Classic Hodgkin lymphoma, mixed cellularity. Diffuse inflammatory background with dispersed Hodgkin/Reed–Sternberg (HRS) cells.
Classic Hodgkin lymphoma, mixed cellularity. The Hodgkin/Reed–Sternberg (HRS) cells express CD30.
Nodular lymphocyte-predominant Hodgkin lymphoma. Nodular pattern with a predominance of small lymphocytes and scattered large atypical lymphocyte-predominant cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. OCT2 immunostaining highlights the nuclei of the lymphocyte-predominant cells in the nodular background.

Q: On histologic examination of Myeloid Sarcoma, the presence of scattered [...] admixed with cells showing immature chromatin provides a highly specific clue for granulocytic differentiation.
Myeloid sarcoma involving orbital fat. The neoplastic cells have thin nuclear membranes and immature chromatin. Rare eosinophilic metamyelocytes are present in this field.
A: eosinophilic metamyelocytes
Back Extra: Myeloid Sarcoma
- Clinical: Patients with myeloid sarcoma may present with a mass, painful throat, bleeding from the nose or mouth, jaw pain, or disturbed vision.
- Micro: Myeloid sarcoma forms a mass that diffusely replaces tissue architecture, often with a single-file pattern, especially in cases with monocytic differentiation.
- Ancillary: Immunophenotypic analysis shows that the neoplastic cells are often positive for CD11c, CD13, CD33, CD34, CD43, CD68, myeloperoxidase, and lysozyme.
Reference Gallery:
Myeloid sarcoma involving gingiva. Myeloid sarcoma with monocytic differentiation infiltrating the gingiva. In many areas the neoplastic cells exhibit a single-file pattern.
Myeloid sarcoma involving gingiva. This myeloid sarcoma shows monocytic differentiation; the neoplastic cells are strongly positive for CD68.
Myeloid sarcoma involving orbital fat. The neoplastic cells have thin nuclear membranes and immature chromatin. Rare eosinophilic metamyelocytes are present in this field.
Myeloid sarcoma involving orbital fat. The neoplastic cells are positive for myeloperoxidase, supporting granulocytic differentiation.

Q: Ancillary testing is essential to confirm Myeloid Sarcoma; cases with granulocytic differentiation are typically positive for [...], whereas those with monocytic differentiation typically strongly express CD68.
Myeloid sarcoma involving gingiva. This myeloid sarcoma shows monocytic differentiation; the neoplastic cells are strongly positive for CD68.
Myeloid sarcoma involving orbital fat. The neoplastic cells are positive for myeloperoxidase, supporting granulocytic differentiation.
A: myeloperoxidase
Back Extra: Myeloid Sarcoma
- Clinical: Patients with myeloid sarcoma may present with a mass, painful throat, bleeding from the nose or mouth, jaw pain, or disturbed vision.
- Micro: Myeloid sarcoma forms a mass that diffusely replaces tissue architecture, often with a single-file pattern, especially in cases with monocytic differentiation.
- Ancillary: Immunophenotypic analysis shows that the neoplastic cells are often positive for CD11c, CD13, CD33, CD34, CD43, CD68, myeloperoxidase, and lysozyme.
Reference Gallery:
Myeloid sarcoma involving gingiva. Myeloid sarcoma with monocytic differentiation infiltrating the gingiva. In many areas the neoplastic cells exhibit a single-file pattern.
Myeloid sarcoma involving gingiva. This myeloid sarcoma shows monocytic differentiation; the neoplastic cells are strongly positive for CD68.
Myeloid sarcoma involving orbital fat. The neoplastic cells have thin nuclear membranes and immature chromatin. Rare eosinophilic metamyelocytes are present in this field.
Myeloid sarcoma involving orbital fat. The neoplastic cells are positive for myeloperoxidase, supporting granulocytic differentiation.

Q: When Myeloid Sarcoma exhibits monocytic differentiation, the neoplastic cells characteristically infiltrate and replace the native tissue architecture in a [...] pattern.
Myeloid sarcoma involving gingiva. Myeloid sarcoma with monocytic differentiation infiltrating the gingiva. In many areas the neoplastic cells exhibit a single-file pattern.
A: single-file
Back Extra: Myeloid Sarcoma
- Clinical: Patients with myeloid sarcoma may present with a mass, painful throat, bleeding from the nose or mouth, jaw pain, or disturbed vision.
- Micro: Myeloid sarcoma forms a mass that diffusely replaces tissue architecture, often with a single-file pattern, especially in cases with monocytic differentiation.
- Ancillary: Immunophenotypic analysis shows that the neoplastic cells are often positive for CD11c, CD13, CD33, CD34, CD43, CD68, myeloperoxidase, and lysozyme.
Reference Gallery:
Myeloid sarcoma involving gingiva. Myeloid sarcoma with monocytic differentiation infiltrating the gingiva. In many areas the neoplastic cells exhibit a single-file pattern.
Myeloid sarcoma involving gingiva. This myeloid sarcoma shows monocytic differentiation; the neoplastic cells are strongly positive for CD68.
Myeloid sarcoma involving orbital fat. The neoplastic cells have thin nuclear membranes and immature chromatin. Rare eosinophilic metamyelocytes are present in this field.
Myeloid sarcoma involving orbital fat. The neoplastic cells are positive for myeloperoxidase, supporting granulocytic differentiation.

Q: Microscopically, an EBV-positive mucocutaneous ulcer consists of a well-circumscribed ulcer with a polymorphous infiltrate at its base that characteristically contains atypical [...] cells.
EBV-positive mucocutaneous ulcer. Low-magnification view of a tonsil shows a well-circumscribed lesion with extensive mucosal ulceration.
EBV-positive mucocutaneous ulcer. High-magnification view shows a mixed inflammatory infiltrate with atypical Hodgkin/Reed–Sternberg (HRS)-like cells.
A: Hodgkin/Reed-Sternberg (HRS)-like
Back Extra: EBV-positive mucocutaneous ulcer
- Clinical: EBV-positive mucocutaneous ulcer typically manifests as well-circumscribed, often painful ulcers in mucosal or cutaneous sites, without systemic symptoms.
- Micro: Microscopically, the lesion shows a well-circumscribed ulcer with a polymorphous infiltrate at the base, containing lymphoid cells, immunoblasts, plasma cells, and HRS-like cells.
- Ancillary: Immunohistochemistry shows a mixture of CD20+ and CD3+ lymphoid cells, with CD30 commonly expressed and EBV positivity confirmed by EBER in situ hybridization.
Reference Gallery:
EBV-positive mucocutaneous ulcer. Low-magnification view of a tonsil shows a well-circumscribed lesion with extensive mucosal ulceration.
EBV-positive mucocutaneous ulcer. High-magnification view shows a mixed inflammatory infiltrate with atypical Hodgkin/Reed–Sternberg (HRS)-like cells.
EBV-positive mucocutaneous ulcer. EBV-encoded small RNA (EBER) in situ hybridization highlights a range of EBV-positive cells.

Q: To confirm the diagnosis of an EBV-positive mucocutaneous ulcer, in situ hybridization for [...] is used to highlight the range of virally infected cells within the mixed inflammatory infiltrate.
EBV-positive mucocutaneous ulcer. EBV-encoded small RNA (EBER) in situ hybridization highlights a range of EBV-positive cells.
A: EBV-encoded small RNA (EBER)
Back Extra: EBV-positive mucocutaneous ulcer
- Clinical: EBV-positive mucocutaneous ulcer typically manifests as well-circumscribed, often painful ulcers in mucosal or cutaneous sites, without systemic symptoms.
- Micro: Microscopically, the lesion shows a well-circumscribed ulcer with a polymorphous infiltrate at the base, containing lymphoid cells, immunoblasts, plasma cells, and HRS-like cells.
- Ancillary: Immunohistochemistry shows a mixture of CD20+ and CD3+ lymphoid cells, with CD30 commonly expressed and EBV positivity confirmed by EBER in situ hybridization.
Reference Gallery:
EBV-positive mucocutaneous ulcer. Low-magnification view of a tonsil shows a well-circumscribed lesion with extensive mucosal ulceration.
EBV-positive mucocutaneous ulcer. High-magnification view shows a mixed inflammatory infiltrate with atypical Hodgkin/Reed–Sternberg (HRS)-like cells.
EBV-positive mucocutaneous ulcer. EBV-encoded small RNA (EBER) in situ hybridization highlights a range of EBV-positive cells.

Q: The characteristic histologic triad of IgG4-related disease consists of a dense lymphoplasmacytic infiltrate, storiform fibrosis, and [...].
IgG4-related sialadenitis. The vein in the right upper field shows fibrosis and transmural inflammatory cell infiltrate (obliterative phlebitis). The accompanying artery in the left lower field is uninvolved.
IgG4-related rhinitis. There are many plasma cells and small lymphocytes, and occasional eosinophils. Note the stromal fibrosis that exhibits a vague storiform appearance.
A: obliterative phlebitis
Back Extra: IgG4-related disease
- Clinical: Subacute presentation with fatigue, weight loss, nasal obstruction, facial swelling, pain, epistaxis, destruction of nasal structures, dysphonia, dyspnoea, stridor, hearing loss, vestibular dysfunction, and headache.
- Micro: Characterized by a lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis.
- Ancillary: Immunostaining shows increased IgG4+ cells and an IgG4+:IgG+ ratio > 40%, with elevated serum IgG4 levels.
Reference Gallery:
IgG4-related sialadenitis. IgG4-related submandibular gland disease with extensive fibrosis and glandular atrophy. Uninvolved parenchyma is present in the left upper field.
IgG4-related sialadenitis. There is a variable lymphoid infiltrate in the parenchyma, and the lobular architecture of the salivary gland is accentuated by septal fibrosis.
IgG4-related sialadenitis. The lymphoid infiltrate comprises plasma cells and small lymphocytes with some reactive lymphoid follicles.
IgG4-related sialadenitis. There is preferential loss of acini and some of the residual ductal structures show periductal fibrosis.
IgG4-related sialadenitis. The lymphoplasmacytic infiltrate typically does not involve the glandular epithelium, i.e. there are no lymphoepithelial lesions.
IgG4-related sialadenitis. The vein in the right upper field shows fibrosis and transmural inflammatory cell infiltrate (obliterative phlebitis). The accompanying artery in the left lower field is uninvolved.
IgG4-related sialadenitis. Immunostaining for IgG4 shows increased IgG4+ cells.
IgG4-related rhinitis. The expanded nasal mucosa shows patchy lymphoid cell infiltrate, reactive follicles, and stromal fibrosis.
IgG4-related rhinitis. There are many plasma cells and small lymphocytes, and occasional eosinophils. Note the stromal fibrosis that exhibits a vague storiform appearance.
IgG4-related rhinitis. Immunostaining for IgG4 shows increased IgG4+ cells.
IgG4-related rhinitis. Immunostaining for IgG. The IgG4+:IgG+ ratio is well above 40%.
IgG4-related sialadenitis. Immunostaining for IgG. The IgG4+:IgG+ ratio is well above 40%.

Q: To confirm a diagnosis of IgG4-related disease, immunohistochemistry typically demonstrates increased IgG4+ plasma cells and an IgG4+ to IgG+ cell ratio greater than [...].
IgG4-related sialadenitis. Immunostaining for IgG4 shows increased IgG4+ cells.
IgG4-related sialadenitis. Immunostaining for IgG. The IgG4+:IgG+ ratio is well above 40%.
A: 40%
Back Extra: IgG4-related disease
- Clinical: Subacute presentation with fatigue, weight loss, nasal obstruction, facial swelling, pain, epistaxis, destruction of nasal structures, dysphonia, dyspnoea, stridor, hearing loss, vestibular dysfunction, and headache.
- Micro: Characterized by a lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis.
- Ancillary: Immunostaining shows increased IgG4+ cells and an IgG4+:IgG+ ratio > 40%, with elevated serum IgG4 levels.
Reference Gallery:
IgG4-related sialadenitis. IgG4-related submandibular gland disease with extensive fibrosis and glandular atrophy. Uninvolved parenchyma is present in the left upper field.
IgG4-related sialadenitis. There is a variable lymphoid infiltrate in the parenchyma, and the lobular architecture of the salivary gland is accentuated by septal fibrosis.
IgG4-related sialadenitis. The lymphoid infiltrate comprises plasma cells and small lymphocytes with some reactive lymphoid follicles.
IgG4-related sialadenitis. There is preferential loss of acini and some of the residual ductal structures show periductal fibrosis.
IgG4-related sialadenitis. The lymphoplasmacytic infiltrate typically does not involve the glandular epithelium, i.e. there are no lymphoepithelial lesions.
IgG4-related sialadenitis. The vein in the right upper field shows fibrosis and transmural inflammatory cell infiltrate (obliterative phlebitis). The accompanying artery in the left lower field is uninvolved.
IgG4-related sialadenitis. Immunostaining for IgG4 shows increased IgG4+ cells.
IgG4-related rhinitis. The expanded nasal mucosa shows patchy lymphoid cell infiltrate, reactive follicles, and stromal fibrosis.
IgG4-related rhinitis. There are many plasma cells and small lymphocytes, and occasional eosinophils. Note the stromal fibrosis that exhibits a vague storiform appearance.
IgG4-related rhinitis. Immunostaining for IgG4 shows increased IgG4+ cells.
IgG4-related rhinitis. Immunostaining for IgG. The IgG4+:IgG+ ratio is well above 40%.
IgG4-related sialadenitis. Immunostaining for IgG. The IgG4+:IgG+ ratio is well above 40%.

Q: When IgG4-related disease involves the salivary glands (sialadenitis), the lymphoplasmacytic infiltrate typically spares the glandular epithelium, resulting in a characteristic absence of [...].
IgG4-related sialadenitis. The lymphoplasmacytic infiltrate typically does not involve the glandular epithelium, i.e. there are no lymphoepithelial lesions.
A: lymphoepithelial lesions
Back Extra: IgG4-related disease
- Clinical: Subacute presentation with fatigue, weight loss, nasal obstruction, facial swelling, pain, epistaxis, destruction of nasal structures, dysphonia, dyspnoea, stridor, hearing loss, vestibular dysfunction, and headache.
- Micro: Characterized by a lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis.
- Ancillary: Immunostaining shows increased IgG4+ cells and an IgG4+:IgG+ ratio > 40%, with elevated serum IgG4 levels.
Reference Gallery:
IgG4-related sialadenitis. IgG4-related submandibular gland disease with extensive fibrosis and glandular atrophy. Uninvolved parenchyma is present in the left upper field.
IgG4-related sialadenitis. There is a variable lymphoid infiltrate in the parenchyma, and the lobular architecture of the salivary gland is accentuated by septal fibrosis.
IgG4-related sialadenitis. The lymphoid infiltrate comprises plasma cells and small lymphocytes with some reactive lymphoid follicles.
IgG4-related sialadenitis. There is preferential loss of acini and some of the residual ductal structures show periductal fibrosis.
IgG4-related sialadenitis. The lymphoplasmacytic infiltrate typically does not involve the glandular epithelium, i.e. there are no lymphoepithelial lesions.
IgG4-related sialadenitis. The vein in the right upper field shows fibrosis and transmural inflammatory cell infiltrate (obliterative phlebitis). The accompanying artery in the left lower field is uninvolved.
IgG4-related sialadenitis. Immunostaining for IgG4 shows increased IgG4+ cells.
IgG4-related rhinitis. The expanded nasal mucosa shows patchy lymphoid cell infiltrate, reactive follicles, and stromal fibrosis.
IgG4-related rhinitis. There are many plasma cells and small lymphocytes, and occasional eosinophils. Note the stromal fibrosis that exhibits a vague storiform appearance.
IgG4-related rhinitis. Immunostaining for IgG4 shows increased IgG4+ cells.
IgG4-related rhinitis. Immunostaining for IgG. The IgG4+:IgG+ ratio is well above 40%.
IgG4-related sialadenitis. Immunostaining for IgG. The IgG4+:IgG+ ratio is well above 40%.

Q: Microscopically, Reactive Lymphoid Hyperplasia can demonstrate follicular hyperplasia or marked paracortical expansion by a [...] lymphoid infiltrate with numerous immunoblasts, which can often mimic lymphoma.
Infectious mononucleosis, tonsil. Several reactive lymphoid follicles are present adjacent to an intact crypt (right of image). Most of the rest of the tissue is replaced and expanded by an interfollicular and diffuse lymphoid proliferation.
Infectious mononucleosis, tonsil. High-power view shows a polymorphous population that includes many immunoblasts, with frequent mitoses.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). Low-power view shows marked paracortical expansion by a lymphohistiocytic infiltrate. Several follicles remain around the periphery of the infiltrate.
A: polymorphous
Back Extra: Reactive Lymphoid Hyperplasia
- Clinical: Patients with reactive lymphoid hyperplasia often present with lymphadenopathy, enlarged tonsils, or mucosal ulceration, with symptoms varying by the underlying cause.
- Micro: Microscopically, reactive lymphoid hyperplasia can show follicular hyperplasia, paracortical hyperplasia, and polymorphous lymphoid infiltrates, which can mimic lymphoma.
- Ancillary: Ancillary studies such as identification of infectious agents by immunohistochemistry, special stains, and molecular techniques are crucial in diagnosing reactive lymphoid hyperplasia.
Reference Gallery:
Infectious mononucleosis, tonsil. Several reactive lymphoid follicles are present adjacent to an intact crypt (right of image). Most of the rest of the tissue is replaced and expanded by an interfollicular and diffuse lymphoid proliferation.
Infectious mononucleosis, tonsil. One reactive follicle (lower right) is surrounded by a florid, polymorphous lymphoid proliferation. A focus of necrosis is present (upper left).
Infectious mononucleosis, tonsil. High-power view shows a polymorphous population that includes many immunoblasts, with frequent mitoses.
Infectious mononucleosis, tonsil. The infiltrate includes occasional Reed–Sternberg–like cells (oil immersion).
Infectious mononucleosis, tonsil. In situ hybridization for EBV-encoded small RNA (EBER) shows numerous EBV+ cells surrounding a follicle composed of cells that are mostly EBV–.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). Low-power view shows marked paracortical expansion by a lymphohistiocytic infiltrate. Several follicles remain around the periphery of the infiltrate.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). Much of the section is occupied by a polymorphous population that includes frequent large lymphoid cells. A portion of a follicle is seen (lower right).
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). In this area of the paracortex, immunoblasts are numerous, potentially mimicking lymphoma. There are also numerous pyknotic nuclei.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). In other areas, histiocytes, including crescentic forms, predominate.

Q: In cases of Reactive Lymphoid Hyperplasia secondary to infectious mononucleosis, the infiltrate can feature numerous immunoblasts and Reed-Sternberg-like cells, with the viral etiology classically confirmed using in situ hybridization for [...].
Infectious mononucleosis, tonsil. The infiltrate includes occasional Reed–Sternberg–like cells (oil immersion).
Infectious mononucleosis, tonsil. In situ hybridization for EBV-encoded small RNA (EBER) shows numerous EBV+ cells surrounding a follicle composed of cells that are mostly EBV–.
A: EBV-encoded small RNA (EBER)
Back Extra: Reactive Lymphoid Hyperplasia
- Clinical: Patients with reactive lymphoid hyperplasia often present with lymphadenopathy, enlarged tonsils, or mucosal ulceration, with symptoms varying by the underlying cause.
- Micro: Microscopically, reactive lymphoid hyperplasia can show follicular hyperplasia, paracortical hyperplasia, and polymorphous lymphoid infiltrates, which can mimic lymphoma.
- Ancillary: Ancillary studies such as identification of infectious agents by immunohistochemistry, special stains, and molecular techniques are crucial in diagnosing reactive lymphoid hyperplasia.
Reference Gallery:
Infectious mononucleosis, tonsil. Several reactive lymphoid follicles are present adjacent to an intact crypt (right of image). Most of the rest of the tissue is replaced and expanded by an interfollicular and diffuse lymphoid proliferation.
Infectious mononucleosis, tonsil. One reactive follicle (lower right) is surrounded by a florid, polymorphous lymphoid proliferation. A focus of necrosis is present (upper left).
Infectious mononucleosis, tonsil. High-power view shows a polymorphous population that includes many immunoblasts, with frequent mitoses.
Infectious mononucleosis, tonsil. The infiltrate includes occasional Reed–Sternberg–like cells (oil immersion).
Infectious mononucleosis, tonsil. In situ hybridization for EBV-encoded small RNA (EBER) shows numerous EBV+ cells surrounding a follicle composed of cells that are mostly EBV–.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). Low-power view shows marked paracortical expansion by a lymphohistiocytic infiltrate. Several follicles remain around the periphery of the infiltrate.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). Much of the section is occupied by a polymorphous population that includes frequent large lymphoid cells. A portion of a follicle is seen (lower right).
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). In this area of the paracortex, immunoblasts are numerous, potentially mimicking lymphoma. There are also numerous pyknotic nuclei.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). In other areas, histiocytes, including crescentic forms, predominate.

Q: Reactive Lymphoid Hyperplasia presenting as histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) features marked paracortical expansion with abundant pyknotic nuclei and a characteristic predominance of [...].
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). In this area of the paracortex, immunoblasts are numerous, potentially mimicking lymphoma. There are also numerous pyknotic nuclei.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). In other areas, histiocytes, including crescentic forms, predominate.
A: crescentic histiocytes
Back Extra: Reactive Lymphoid Hyperplasia
- Clinical: Patients with reactive lymphoid hyperplasia often present with lymphadenopathy, enlarged tonsils, or mucosal ulceration, with symptoms varying by the underlying cause.
- Micro: Microscopically, reactive lymphoid hyperplasia can show follicular hyperplasia, paracortical hyperplasia, and polymorphous lymphoid infiltrates, which can mimic lymphoma.
- Ancillary: Ancillary studies such as identification of infectious agents by immunohistochemistry, special stains, and molecular techniques are crucial in diagnosing reactive lymphoid hyperplasia.
Reference Gallery:
Infectious mononucleosis, tonsil. Several reactive lymphoid follicles are present adjacent to an intact crypt (right of image). Most of the rest of the tissue is replaced and expanded by an interfollicular and diffuse lymphoid proliferation.
Infectious mononucleosis, tonsil. One reactive follicle (lower right) is surrounded by a florid, polymorphous lymphoid proliferation. A focus of necrosis is present (upper left).
Infectious mononucleosis, tonsil. High-power view shows a polymorphous population that includes many immunoblasts, with frequent mitoses.
Infectious mononucleosis, tonsil. The infiltrate includes occasional Reed–Sternberg–like cells (oil immersion).
Infectious mononucleosis, tonsil. In situ hybridization for EBV-encoded small RNA (EBER) shows numerous EBV+ cells surrounding a follicle composed of cells that are mostly EBV–.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). Low-power view shows marked paracortical expansion by a lymphohistiocytic infiltrate. Several follicles remain around the periphery of the infiltrate.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). Much of the section is occupied by a polymorphous population that includes frequent large lymphoid cells. A portion of a follicle is seen (lower right).
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). In this area of the paracortex, immunoblasts are numerous, potentially mimicking lymphoma. There are also numerous pyknotic nuclei.
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). In other areas, histiocytes, including crescentic forms, predominate.

Q: Histologically, Extranodal NK/T-cell lymphoma is characterized by prominent tissue necrosis and a characteristic [...] growth pattern, resulting in the infiltration and destruction of blood vessel walls.
Extranodal NK/T-cell lymphoma. The tumour frequently demonstrates prominent necrosis.
Extranodal NK/T-cell lymphoma. The tumour cells display a characteristic angiocentric growth pattern with infiltration and destruction of a muscular blood vessel wall.
A: angiocentric
Back Extra: Extranodal NK/T-cell lymphoma
- Clinical: Extranodal NK/T-cell lymphoma commonly presents with nasal obstruction, epistaxis, and necrotizing lesions of the nose or hard palate.
- Micro: Characterized by a polymorphous infiltration of neoplastic cells with extensive necrosis and angiocentric growth.
- Ancillary: EBV-encoded small RNA (EBER) in situ hybridization reveals EBV infection in virtually all tumour cells.
Reference Gallery:
Extranodal NK/T-cell lymphoma. The nasal tumour invades adjacent tissue and penetrates overlying skin.
Extranodal NK/T-cell lymphoma. The tumour in the nasal cavity extends to the orbit, resulting in proptosis.
Extranodal NK/T-cell lymphoma. The tumour frequently demonstrates prominent necrosis.
Extranodal NK/T-cell lymphoma. In the nasal mucosa, extranodal NK/T-cell lymphoma can be associated with florid pseudoepitheliomatous hyperplasia of the overlying squamous epithelium.
Extranodal NK/T-cell lymphoma. The tumour cells display a characteristic angiocentric growth pattern with infiltration and destruction of a muscular blood vessel wall.
Extranodal NK/T-cell lymphoma. The tumour cells are positive for CD3.
Extranodal NK/T-cell lymphoma. The tumour cells are positive for CD56.
Extranodal NK/T-cell lymphoma. The tumour cells are positive for granzyme B.
Extranodal NK/T-cell lymphoma. Almost all tumour cells are positive for EBV-encoded small RNA (EBER) by in situ hybridization.
Extranodal NK/T-cell lymphoma. The lymphoma shows medium to large tumour cells with irregular and often hyperchromatic nuclei.

Q: Virtually all cases of Extranodal NK/T-cell lymphoma are driven by an underlying infection with [...], which is typically detected using EBER in situ hybridization.
Extranodal NK/T-cell lymphoma. Almost all tumour cells are positive for EBV-encoded small RNA (EBER) by in situ hybridization.
A: Epstein-Barr virus (EBV)
Back Extra: Extranodal NK/T-cell lymphoma
- Clinical: Extranodal NK/T-cell lymphoma commonly presents with nasal obstruction, epistaxis, and necrotizing lesions of the nose or hard palate.
- Micro: Characterized by a polymorphous infiltration of neoplastic cells with extensive necrosis and angiocentric growth.
- Ancillary: EBV-encoded small RNA (EBER) in situ hybridization reveals EBV infection in virtually all tumour cells.
Reference Gallery:
Extranodal NK/T-cell lymphoma. The nasal tumour invades adjacent tissue and penetrates overlying skin.
Extranodal NK/T-cell lymphoma. The tumour in the nasal cavity extends to the orbit, resulting in proptosis.
Extranodal NK/T-cell lymphoma. The tumour frequently demonstrates prominent necrosis.
Extranodal NK/T-cell lymphoma. In the nasal mucosa, extranodal NK/T-cell lymphoma can be associated with florid pseudoepitheliomatous hyperplasia of the overlying squamous epithelium.
Extranodal NK/T-cell lymphoma. The tumour cells display a characteristic angiocentric growth pattern with infiltration and destruction of a muscular blood vessel wall.
Extranodal NK/T-cell lymphoma. The tumour cells are positive for CD3.
Extranodal NK/T-cell lymphoma. The tumour cells are positive for CD56.
Extranodal NK/T-cell lymphoma. The tumour cells are positive for granzyme B.
Extranodal NK/T-cell lymphoma. Almost all tumour cells are positive for EBV-encoded small RNA (EBER) by in situ hybridization.
Extranodal NK/T-cell lymphoma. The lymphoma shows medium to large tumour cells with irregular and often hyperchromatic nuclei.

Q: Clinically, Extranodal NK/T-cell lymphoma often presents as an aggressive, necrotizing tumor classically localized to the [...] and upper aerodigestive tract.
Extranodal NK/T-cell lymphoma. The nasal tumour invades adjacent tissue and penetrates overlying skin.
Extranodal NK/T-cell lymphoma. The tumour in the nasal cavity extends to the orbit, resulting in proptosis.
A: nasal cavity
Back Extra: Extranodal NK/T-cell lymphoma
- Clinical: Extranodal NK/T-cell lymphoma commonly presents with nasal obstruction, epistaxis, and necrotizing lesions of the nose or hard palate.
- Micro: Characterized by a polymorphous infiltration of neoplastic cells with extensive necrosis and angiocentric growth.
- Ancillary: EBV-encoded small RNA (EBER) in situ hybridization reveals EBV infection in virtually all tumour cells.
Reference Gallery:
Extranodal NK/T-cell lymphoma. The nasal tumour invades adjacent tissue and penetrates overlying skin.
Extranodal NK/T-cell lymphoma. The tumour in the nasal cavity extends to the orbit, resulting in proptosis.
Extranodal NK/T-cell lymphoma. The tumour frequently demonstrates prominent necrosis.
Extranodal NK/T-cell lymphoma. In the nasal mucosa, extranodal NK/T-cell lymphoma can be associated with florid pseudoepitheliomatous hyperplasia of the overlying squamous epithelium.
Extranodal NK/T-cell lymphoma. The tumour cells display a characteristic angiocentric growth pattern with infiltration and destruction of a muscular blood vessel wall.
Extranodal NK/T-cell lymphoma. The tumour cells are positive for CD3.
Extranodal NK/T-cell lymphoma. The tumour cells are positive for CD56.
Extranodal NK/T-cell lymphoma. The tumour cells are positive for granzyme B.
Extranodal NK/T-cell lymphoma. Almost all tumour cells are positive for EBV-encoded small RNA (EBER) by in situ hybridization.
Extranodal NK/T-cell lymphoma. The lymphoma shows medium to large tumour cells with irregular and often hyperchromatic nuclei.

Q: Histologically, [...] is characterized by sheets of large atypical lymphoid cells with abundant pale eosinophilic cytoplasm, often set within a mixed inflammatory background containing numerous eosinophils.
Primary CD30-positive T-cell lymphoproliferative disorder of the buccal mucosa. The tumour is composed of sheets of large neoplastic cells with abundant pale eosinophilic cytoplasm.
Primary CD30-positive T-cell lymphoproliferative disorder of the tongue. The neoplastic cells are present within an inflammatory background containing numerous eosinophils.
A: Primary Mucosal CD30-Positive T-Cell Lymphoproliferative Disorder
Back Extra: Primary Mucosal CD30-Positive T-Cell Lymphoproliferative Disorder
- Clinical: Patients with Primary Mucosal CD30-Positive T-Cell Lymphoproliferative Disorder typically present with a mass lesion, often with ulceration, and a male predominance (M:F ratio: 2:1).
- Micro: The disorder shows a morphological spectrum with large atypical lymphoid cells, strong and uniform CD30 positivity, and a mixed inflammatory background.
- Ancillary: TR gene rearrangement studies are useful in establishing clonality, and occasional cases may have rearrangements of DUSP22 on 6p25.3.
Reference Gallery:
Primary CD30-positive T-cell lymphoproliferative disorder of the buccal mucosa. There is extensive infiltration of the mucosa, with superficial ulceration.
Primary CD30-positive T-cell lymphoproliferative disorder of the buccal mucosa. The tumour is composed of sheets of large neoplastic cells with abundant pale eosinophilic cytoplasm.
Primary CD30-positive T-cell lymphoproliferative disorder of the tongue. There is marked ulceration with deep infiltration of the muscle.
Primary CD30-positive T-cell lymphoproliferative disorder of the tongue. The neoplastic cells are present within an inflammatory background containing numerous eosinophils.

Q: Patients with [...] frequently present with an infiltrating mucosal mass lesion (e.g., buccal mucosa or tongue) that is typically accompanied by marked superficial ulceration.
Primary CD30-positive T-cell lymphoproliferative disorder of the buccal mucosa. There is extensive infiltration of the mucosa, with superficial ulceration.
Primary CD30-positive T-cell lymphoproliferative disorder of the tongue. There is marked ulceration with deep infiltration of the muscle.
A: Primary Mucosal CD30-Positive T-Cell Lymphoproliferative Disorder
Back Extra: Primary Mucosal CD30-Positive T-Cell Lymphoproliferative Disorder
- Clinical: Patients with Primary Mucosal CD30-Positive T-Cell Lymphoproliferative Disorder typically present with a mass lesion, often with ulceration, and a male predominance (M:F ratio: 2:1).
- Micro: The disorder shows a morphological spectrum with large atypical lymphoid cells, strong and uniform CD30 positivity, and a mixed inflammatory background.
- Ancillary: TR gene rearrangement studies are useful in establishing clonality, and occasional cases may have rearrangements of DUSP22 on 6p25.3.
Reference Gallery:
Primary CD30-positive T-cell lymphoproliferative disorder of the buccal mucosa. There is extensive infiltration of the mucosa, with superficial ulceration.
Primary CD30-positive T-cell lymphoproliferative disorder of the buccal mucosa. The tumour is composed of sheets of large neoplastic cells with abundant pale eosinophilic cytoplasm.
Primary CD30-positive T-cell lymphoproliferative disorder of the tongue. There is marked ulceration with deep infiltration of the muscle.
Primary CD30-positive T-cell lymphoproliferative disorder of the tongue. The neoplastic cells are present within an inflammatory background containing numerous eosinophils.

Q: Microscopic examination of T-lymphoblastic leukemia/lymphoma reveals a diffuse infiltrate of medium-sized blasts with immature chromatin, often forming a [...] pattern due to scattered tingible-body macrophages.
T-lymphoblastic lymphoma. High-power view reveals medium-sized blasts with immature chromatin and small nucleoli.
T-lymphoblastic leukaemia. There is a diffuse infiltrate of medium-sized lymphoid cells with delicate chromatin and small to inconspicuous nucleoli. Scattered tingible-body macrophages impart a starry-sky pattern.
A: starry-sky
Back Extra: T-lymphoblastic leukaemia/lymphoma
- Clinical: T-lymphoblastic leukaemia/lymphoma (T-ALL/LBL) primarily affects children and young adults, presenting with symptoms such as dyspnoea, superior vena cava syndrome, and pleural/pericardial effusions.
- Micro: High-power views reveal medium-sized blasts with immature chromatin and small nucleoli, often forming a starry-sky pattern due to scattered tingible-body macrophages.
- Ancillary: Flow cytometry typically shows positivity for cytoplasmic CD3, CD7, CD34, and TdT, with frequent clonal rearrangements of TRB and/or TRG.
Reference Gallery:
T-lymphoblastic lymphoma. High-power view reveals medium-sized blasts with immature chromatin and small nucleoli.
T-lymphoblastic lymphoma. The neoplastic cells express CD1a.
T-lymphoblastic lymphoma. The neoplastic cells are positive for TdT.
T-lymphoblastic lymphoma. The neoplastic cells express NOTCH1.
T-lymphoblastic lymphoma. Ki-67 staining labels > 90% of cells.
T-lymphoblastic leukaemia. There is a diffuse infiltrate of medium-sized lymphoid cells with delicate chromatin and small to inconspicuous nucleoli. Scattered tingible-body macrophages impart a starry-sky pattern.
T-lymphoblastic leukaemia/lymphoma, early T-precursor phenotype. Flow cytometry shows that the neoplastic cells are positive for cytoplasmic CD3, CD7, CD33 (not shown), CD34, KIT (CD117) (partial), and TdT; and negative for CD1a, CD2 (not shown), sCD3, CD4, CD8, CD13, and myeloperoxidase (MPO).

Q: The neoplastic blasts in T-lymphoblastic leukemia/lymphoma are characteristically positive for immature lymphoid markers, including CD34 and [...].
T-lymphoblastic lymphoma. The neoplastic cells are positive for TdT.
T-lymphoblastic leukaemia/lymphoma, early T-precursor phenotype. Flow cytometry shows that the neoplastic cells are positive for cytoplasmic CD3, CD7, CD33 (not shown), CD34, KIT (CD117) (partial), and TdT; and negative for CD1a, CD2 (not shown), sCD3, CD4, CD8, CD13, and myeloperoxidase (MPO).
A: terminal deoxynucleotidyl transferase (TdT)
Back Extra: T-lymphoblastic leukaemia/lymphoma
- Clinical: T-lymphoblastic leukaemia/lymphoma (T-ALL/LBL) primarily affects children and young adults, presenting with symptoms such as dyspnoea, superior vena cava syndrome, and pleural/pericardial effusions.
- Micro: High-power views reveal medium-sized blasts with immature chromatin and small nucleoli, often forming a starry-sky pattern due to scattered tingible-body macrophages.
- Ancillary: Flow cytometry typically shows positivity for cytoplasmic CD3, CD7, CD34, and TdT, with frequent clonal rearrangements of TRB and/or TRG.
Reference Gallery:
T-lymphoblastic lymphoma. High-power view reveals medium-sized blasts with immature chromatin and small nucleoli.
T-lymphoblastic lymphoma. The neoplastic cells express CD1a.
T-lymphoblastic lymphoma. The neoplastic cells are positive for TdT.
T-lymphoblastic lymphoma. The neoplastic cells express NOTCH1.
T-lymphoblastic lymphoma. Ki-67 staining labels > 90% of cells.
T-lymphoblastic leukaemia. There is a diffuse infiltrate of medium-sized lymphoid cells with delicate chromatin and small to inconspicuous nucleoli. Scattered tingible-body macrophages impart a starry-sky pattern.
T-lymphoblastic leukaemia/lymphoma, early T-precursor phenotype. Flow cytometry shows that the neoplastic cells are positive for cytoplasmic CD3, CD7, CD33 (not shown), CD34, KIT (CD117) (partial), and TdT; and negative for CD1a, CD2 (not shown), sCD3, CD4, CD8, CD13, and myeloperoxidase (MPO).

Q: The neoplastic cells in T-lymphoblastic leukemia/lymphoma typically exhibit a very high proliferation index, with [...] staining often labeling > 90% of the cells.
T-lymphoblastic lymphoma. Ki-67 staining labels > 90% of cells.
A: Ki-67
Back Extra: T-lymphoblastic leukaemia/lymphoma
- Clinical: T-lymphoblastic leukaemia/lymphoma (T-ALL/LBL) primarily affects children and young adults, presenting with symptoms such as dyspnoea, superior vena cava syndrome, and pleural/pericardial effusions.
- Micro: High-power views reveal medium-sized blasts with immature chromatin and small nucleoli, often forming a starry-sky pattern due to scattered tingible-body macrophages.
- Ancillary: Flow cytometry typically shows positivity for cytoplasmic CD3, CD7, CD34, and TdT, with frequent clonal rearrangements of TRB and/or TRG.
Reference Gallery:
T-lymphoblastic lymphoma. High-power view reveals medium-sized blasts with immature chromatin and small nucleoli.
T-lymphoblastic lymphoma. The neoplastic cells express CD1a.
T-lymphoblastic lymphoma. The neoplastic cells are positive for TdT.
T-lymphoblastic lymphoma. The neoplastic cells express NOTCH1.
T-lymphoblastic lymphoma. Ki-67 staining labels > 90% of cells.
T-lymphoblastic leukaemia. There is a diffuse infiltrate of medium-sized lymphoid cells with delicate chromatin and small to inconspicuous nucleoli. Scattered tingible-body macrophages impart a starry-sky pattern.
T-lymphoblastic leukaemia/lymphoma, early T-precursor phenotype. Flow cytometry shows that the neoplastic cells are positive for cytoplasmic CD3, CD7, CD33 (not shown), CD34, KIT (CD117) (partial), and TdT; and negative for CD1a, CD2 (not shown), sCD3, CD4, CD8, CD13, and myeloperoxidase (MPO).

Q: Histologically, Adenosquamous Carcinoma exhibits a biphasic morphology characterized by distinct, adjacent areas of both malignant squamous differentiation and malignant [...] differentiation.
Adenosquamous carcinoma. Low-magnification view showing distinct areas of squamous carcinoma (right) and adenocarcinoma (left). The latter shows tubular structures and necrosis.
Adenosquamous carcinoma. Higher-magnification view showing squamous carcinoma (right) and adenocarcinoma (left) adjacent to each other.
A: glandular
Back Extra: Adenosquamous Carcinoma
- Clinical: Adenosquamous carcinoma (ASC) is rare and affects men 2–4 times as frequently as women, with a peak incidence in the seventh and eighth decades of life.
- Micro: ASC shows a biphasic morphology with distinct areas of squamous and glandular differentiation, often with necrosis and vascular invasion.
- Ancillary: The CRTC1::MAML2 translocation is important in distinguishing ASC from mucoepidermoid carcinoma (MEC), where the MAML2 translocation excludes the diagnosis of ASC.
Reference Gallery:
Adenosquamous carcinoma. Low-magnification view showing distinct areas of squamous carcinoma (right) and adenocarcinoma (left). The latter shows tubular structures and necrosis.
Adenosquamous carcinoma. Higher-magnification view showing squamous carcinoma (right) and adenocarcinoma (left) adjacent to each other.
Adenosquamous carcinoma. Higher-magnification view showing squamous carcinoma (lower-right corner) and adenocarcinoma (upper-right corner and left side) with necrosis.

Q: To distinguish Adenosquamous Carcinoma from mucoepidermoid carcinoma, molecular testing is crucial because the presence of the [MAML2] translocation excludes the diagnosis of Adenosquamous Carcinoma.
Adenosquamous carcinoma. Higher-magnification view showing squamous carcinoma (lower-right corner) and adenocarcinoma (upper-right corner and left side) with necrosis.
A: CRTC1
Back Extra: Adenosquamous Carcinoma
- Clinical: Adenosquamous carcinoma (ASC) is rare and affects men 2–4 times as frequently as women, with a peak incidence in the seventh and eighth decades of life.
- Micro: ASC shows a biphasic morphology with distinct areas of squamous and glandular differentiation, often with necrosis and vascular invasion.
- Ancillary: The CRTC1::MAML2 translocation is important in distinguishing ASC from mucoepidermoid carcinoma (MEC), where the MAML2 translocation excludes the diagnosis of ASC.
Reference Gallery:
Adenosquamous carcinoma. Low-magnification view showing distinct areas of squamous carcinoma (right) and adenocarcinoma (left). The latter shows tubular structures and necrosis.
Adenosquamous carcinoma. Higher-magnification view showing squamous carcinoma (right) and adenocarcinoma (left) adjacent to each other.
Adenosquamous carcinoma. Higher-magnification view showing squamous carcinoma (lower-right corner) and adenocarcinoma (upper-right corner and left side) with necrosis.

Q: Histologically, Basaloid Squamous Cell Carcinoma is characterized by compact basaloid nests with high N:C ratios that frequently form a characteristic [...]–like arrangement, often accompanied by comedonecrosis and abrupt keratinization.
Basaloid squamous cell carcinoma. The tumour is characterized by compact solid nests and trabeculae of basaloid cells arranged in a jigsaw puzzle–like arrangement, separated by myxoid stroma. Abrupt keratinization (centre) and comedonecrosis (upper-right corner) are observed.
Basaloid squamous cell carcinoma. This classic example consists primarily of infiltrative basaloid nests with comedonecrosis. There is a frequent jigsaw puzzle–like arrangement, with compact basaloid nests separated by thin strands of hyaline material.
A: jigsaw puzzle
Back Extra: Basaloid Squamous Cell Carcinoma
- Clinical: Basaloid Squamous Cell Carcinoma (BSCC) often presents with symptoms such as haemoptysis, dysphagia, neck mass, cough, hoarseness, and otalgia, and is more common in older White men.
- Micro: BSCC is characterized by compact basaloid nests with high N:C ratios, frequent peripheral palisading, and a jigsaw puzzle–like arrangement. It also shows frequent comedonecrosis and abrupt keratinization.
- Ancillary: BSCC is diffusely positive for squamous markers (p40, p63, CK5/6) and negative for neuroendocrine markers (synaptophysin, chromogranin, INSM1), SMA, S100, and TTF1.
Reference Gallery:
Basaloid squamous cell carcinoma. The tumour is characterized by compact solid nests and trabeculae of basaloid cells arranged in a jigsaw puzzle–like arrangement, separated by myxoid stroma. Abrupt keratinization (centre) and comedonecrosis (upper-right corner) are observed.
Basaloid squamous cell carcinoma. Within one of the basaloid nests are numerous deposits of hyaline basement membrane–like material, resulting in a pseudocribriform appearance. The tumour cells are pleomorphic, with vesicular chromatin and prominent nucleoli.
Basaloid squamous cell carcinoma. The tumour is characteristically positive for p40 in a strong, diffuse pattern, which helps to distinguish it from mimics like adenoid cystic carcinoma and small cell carcinoma.
Basaloid squamous cell carcinoma. This classic example consists primarily of infiltrative basaloid nests with comedonecrosis. There is a frequent jigsaw puzzle–like arrangement, with compact basaloid nests separated by thin strands of hyaline material.

Q: To distinguish Basaloid Squamous Cell Carcinoma from mimics like small cell carcinoma or adenoid cystic carcinoma, immunohistochemistry characteristically demonstrates strong, diffuse positivity for the squamous marker [...].
Basaloid squamous cell carcinoma. The tumour is characteristically positive for p40 in a strong, diffuse pattern, which helps to distinguish it from mimics like adenoid cystic carcinoma and small cell carcinoma.
A: p40
Back Extra: Basaloid Squamous Cell Carcinoma
- Clinical: Basaloid Squamous Cell Carcinoma (BSCC) often presents with symptoms such as haemoptysis, dysphagia, neck mass, cough, hoarseness, and otalgia, and is more common in older White men.
- Micro: BSCC is characterized by compact basaloid nests with high N:C ratios, frequent peripheral palisading, and a jigsaw puzzle–like arrangement. It also shows frequent comedonecrosis and abrupt keratinization.
- Ancillary: BSCC is diffusely positive for squamous markers (p40, p63, CK5/6) and negative for neuroendocrine markers (synaptophysin, chromogranin, INSM1), SMA, S100, and TTF1.
Reference Gallery:
Basaloid squamous cell carcinoma. The tumour is characterized by compact solid nests and trabeculae of basaloid cells arranged in a jigsaw puzzle–like arrangement, separated by myxoid stroma. Abrupt keratinization (centre) and comedonecrosis (upper-right corner) are observed.
Basaloid squamous cell carcinoma. Within one of the basaloid nests are numerous deposits of hyaline basement membrane–like material, resulting in a pseudocribriform appearance. The tumour cells are pleomorphic, with vesicular chromatin and prominent nucleoli.
Basaloid squamous cell carcinoma. The tumour is characteristically positive for p40 in a strong, diffuse pattern, which helps to distinguish it from mimics like adenoid cystic carcinoma and small cell carcinoma.
Basaloid squamous cell carcinoma. This classic example consists primarily of infiltrative basaloid nests with comedonecrosis. There is a frequent jigsaw puzzle–like arrangement, with compact basaloid nests separated by thin strands of hyaline material.

Q: In Basaloid Squamous Cell Carcinoma, the basaloid nests may contain deposits of hyaline basement membrane–like material, resulting in a characteristic [...] appearance.
Basaloid squamous cell carcinoma. Within one of the basaloid nests are numerous deposits of hyaline basement membrane–like material, resulting in a pseudocribriform appearance. The tumour cells are pleomorphic, with vesicular chromatin and prominent nucleoli.
A: pseudocribriform
Back Extra: Basaloid Squamous Cell Carcinoma
- Clinical: Basaloid Squamous Cell Carcinoma (BSCC) often presents with symptoms such as haemoptysis, dysphagia, neck mass, cough, hoarseness, and otalgia, and is more common in older White men.
- Micro: BSCC is characterized by compact basaloid nests with high N:C ratios, frequent peripheral palisading, and a jigsaw puzzle–like arrangement. It also shows frequent comedonecrosis and abrupt keratinization.
- Ancillary: BSCC is diffusely positive for squamous markers (p40, p63, CK5/6) and negative for neuroendocrine markers (synaptophysin, chromogranin, INSM1), SMA, S100, and TTF1.
Reference Gallery:
Basaloid squamous cell carcinoma. The tumour is characterized by compact solid nests and trabeculae of basaloid cells arranged in a jigsaw puzzle–like arrangement, separated by myxoid stroma. Abrupt keratinization (centre) and comedonecrosis (upper-right corner) are observed.
Basaloid squamous cell carcinoma. Within one of the basaloid nests are numerous deposits of hyaline basement membrane–like material, resulting in a pseudocribriform appearance. The tumour cells are pleomorphic, with vesicular chromatin and prominent nucleoli.
Basaloid squamous cell carcinoma. The tumour is characteristically positive for p40 in a strong, diffuse pattern, which helps to distinguish it from mimics like adenoid cystic carcinoma and small cell carcinoma.
Basaloid squamous cell carcinoma. This classic example consists primarily of infiltrative basaloid nests with comedonecrosis. There is a frequent jigsaw puzzle–like arrangement, with compact basaloid nests separated by thin strands of hyaline material.

Q: Microscopically, Conventional Squamous Cell Carcinoma features infiltrating nests of tumor cells with distinct squamous differentiation, characteristically showing keratin pearls and [...].
Conventional squamous cell carcinoma, well differentiated. At low magnification, infiltrating nests show squamous maturation resembling normal squamous epithelium. Stromal reaction is light.
Conventional squamous cell carcinoma, moderately differentiated. At a higher magnification, nuclear atypia is seen, with obvious signs of squamous differentiation (keratinization and intercellular bridges). Mitoses are present in the centre of the nests.
A: intercellular bridges
Back Extra: Conventional Squamous Cell Carcinoma
- Clinical: Hoarseness is the most common presenting symptom for glottic tumours, while dysphagia and odynophagia are common in hypopharyngeal tumours.
- Micro: Tumour cells grow in irregular nests with stromal invasion, showing squamous differentiation with keratin pearls and intercellular bridges.
- Ancillary: SCCs are positive for cytokeratins (e.g., AE1/AE3, CK5, CK5/6, CK14, and CK19) and nuclear positivity for p63 and p40.
Reference Gallery:
Conventional squamous cell carcinoma, macroscopic appearance. Supraglottic. Exophytic and ulcerated tumour with granular surface of the epiglottis.
Conventional squamous cell carcinoma, macroscopic appearance. Glottic. The tumour extends through both vocal cords, affecting the anterior commissure.
Conventional squamous cell carcinoma, macroscopic appearance. Hypopharyngeal. Large exophytic and ulcerated tumour involving the left piriform sinus.
Conventional squamous cell carcinoma infiltrating the thyroid gland. Cross-sections of a glottic carcinoma extending through the supraglottic compartment and thyroid cartilage into the thyroid gland.
Conventional squamous cell carcinoma. Strong and weak membranous immunohistochemical positivity of PDL1, obtained with the anti-PDL1 22C3 antibody.
Conventional squamous cell carcinoma, well differentiated. At low magnification, infiltrating nests show squamous maturation resembling normal squamous epithelium. Stromal reaction is light.
Conventional squamous cell carcinoma, well differentiated. Cell shape varies according to its position within the nest. At the periphery, the cells are smaller, with higher N:C ratios. At the centre, the cells show large eosinophilic cytoplasm, with low N:C ratios.
Conventional squamous cell carcinoma, well differentiated. Nuclei are slightly pleomorphic, with open chromatin. Nucleoli are frequent. Mitoses are sparse and located at the nest margins. Atypical mitoses are not characteristic of well-differentiated tumours.
Conventional squamous cell carcinoma, moderately differentiated. An invasive growth pattern is clearly seen at low magnification.
Conventional squamous cell carcinoma, moderately differentiated. An infiltrative growth pattern is evident at the invasive front.
Conventional squamous cell carcinoma, moderately differentiated. At a higher magnification, nuclear atypia is seen, with obvious signs of squamous differentiation (keratinization and intercellular bridges). Mitoses are present in the centre of the nests.
Conventional squamous cell carcinoma, poorly differentiated. The tumour cells show a high N:C ratio.

Q: Clinically, a glottic Conventional Squamous Cell Carcinoma that involves the vocal cords most commonly presents with [...], whereas hypopharyngeal tumors frequently cause dysphagia and odynophagia.
Conventional squamous cell carcinoma, macroscopic appearance. Glottic. The tumour extends through both vocal cords, affecting the anterior commissure.
A: hoarseness
Back Extra: Conventional Squamous Cell Carcinoma
- Clinical: Hoarseness is the most common presenting symptom for glottic tumours, while dysphagia and odynophagia are common in hypopharyngeal tumours.
- Micro: Tumour cells grow in irregular nests with stromal invasion, showing squamous differentiation with keratin pearls and intercellular bridges.
- Ancillary: SCCs are positive for cytokeratins (e.g., AE1/AE3, CK5, CK5/6, CK14, and CK19) and nuclear positivity for p63 and p40.
Reference Gallery:
Conventional squamous cell carcinoma, macroscopic appearance. Supraglottic. Exophytic and ulcerated tumour with granular surface of the epiglottis.
Conventional squamous cell carcinoma, macroscopic appearance. Glottic. The tumour extends through both vocal cords, affecting the anterior commissure.
Conventional squamous cell carcinoma, macroscopic appearance. Hypopharyngeal. Large exophytic and ulcerated tumour involving the left piriform sinus.
Conventional squamous cell carcinoma infiltrating the thyroid gland. Cross-sections of a glottic carcinoma extending through the supraglottic compartment and thyroid cartilage into the thyroid gland.
Conventional squamous cell carcinoma. Strong and weak membranous immunohistochemical positivity of PDL1, obtained with the anti-PDL1 22C3 antibody.
Conventional squamous cell carcinoma, well differentiated. At low magnification, infiltrating nests show squamous maturation resembling normal squamous epithelium. Stromal reaction is light.
Conventional squamous cell carcinoma, well differentiated. Cell shape varies according to its position within the nest. At the periphery, the cells are smaller, with higher N:C ratios. At the centre, the cells show large eosinophilic cytoplasm, with low N:C ratios.
Conventional squamous cell carcinoma, well differentiated. Nuclei are slightly pleomorphic, with open chromatin. Nucleoli are frequent. Mitoses are sparse and located at the nest margins. Atypical mitoses are not characteristic of well-differentiated tumours.
Conventional squamous cell carcinoma, moderately differentiated. An invasive growth pattern is clearly seen at low magnification.
Conventional squamous cell carcinoma, moderately differentiated. An infiltrative growth pattern is evident at the invasive front.
Conventional squamous cell carcinoma, moderately differentiated. At a higher magnification, nuclear atypia is seen, with obvious signs of squamous differentiation (keratinization and intercellular bridges). Mitoses are present in the centre of the nests.
Conventional squamous cell carcinoma, poorly differentiated. The tumour cells show a high N:C ratio.

Q: Histologically, Lymphoepithelial Carcinoma exhibits a syncytial growth pattern of large tumor cells with vesicular chromatin and prominent nucleoli, which are characteristically accompanied by an intense [...] inflammatory infiltrate.
Lymphoepithelial carcinoma. The tumour is composed of large cells with indistinct cell borders and round nuclei with vesicular chromatin and prominent nucleoli, along with an intense infiltrate of chronic inflammatory cells.
A: lymphoplasmacytic
Back Extra: Lymphoepithelial Carcinoma
- Clinical: Lymphoepithelial carcinoma (LEC) often presents with hoarseness, neck mass, dysphonia, dysphagia, neck pain, and/or haemoptysis. It is rare, with < 50 reported cases, and mostly affects older males (mean: 62 years) of White descent.
- Micro: LEC is characterized by a sheet-like or nested architecture with syncytial growth, prominent lymphoplasmacytic cell infiltrate, and tumour cells with vesicular chromatin and prominent nucleoli.
- Ancillary: LEC is diffusely positive for pancytokeratin and usually positive for CK5/6 and p40/p63. It is almost always negative for EBV but can harbor high-risk HPV. TP53 mutations are frequently present.
Reference Gallery:
Lymphoepithelial carcinoma. The tumour is composed of large cells with indistinct cell borders and round nuclei with vesicular chromatin and prominent nucleoli, along with an intense infiltrate of chronic inflammatory cells.
Lymphoepithelial carcinoma. The carcinoma expresses cytokeratins (AE1/AE3 immunocytochemistry).
Lymphoepithelial carcinoma. The carcinoma shows strong nuclear expression of p40.

Q: Immunohistochemically, Lymphoepithelial Carcinoma is diffusely positive for pancytokeratins (e.g., AE1/AE3) and typically demonstrates strong nuclear expression for the squamous markers p63 and [...].
Lymphoepithelial carcinoma. The carcinoma expresses cytokeratins (AE1/AE3 immunocytochemistry).
Lymphoepithelial carcinoma. The carcinoma shows strong nuclear expression of p40.
A: p40
Back Extra: Lymphoepithelial Carcinoma
- Clinical: Lymphoepithelial carcinoma (LEC) often presents with hoarseness, neck mass, dysphonia, dysphagia, neck pain, and/or haemoptysis. It is rare, with < 50 reported cases, and mostly affects older males (mean: 62 years) of White descent.
- Micro: LEC is characterized by a sheet-like or nested architecture with syncytial growth, prominent lymphoplasmacytic cell infiltrate, and tumour cells with vesicular chromatin and prominent nucleoli.
- Ancillary: LEC is diffusely positive for pancytokeratin and usually positive for CK5/6 and p40/p63. It is almost always negative for EBV but can harbor high-risk HPV. TP53 mutations are frequently present.
Reference Gallery:
Lymphoepithelial carcinoma. The tumour is composed of large cells with indistinct cell borders and round nuclei with vesicular chromatin and prominent nucleoli, along with an intense infiltrate of chronic inflammatory cells.
Lymphoepithelial carcinoma. The carcinoma expresses cytokeratins (AE1/AE3 immunocytochemistry).
Lymphoepithelial carcinoma. The carcinoma shows strong nuclear expression of p40.

Q: Histologically, Papillary Squamous Cell Carcinoma is characterized by numerous complex, delicate papillae covered by a [...] that lacks maturation and exhibits increased mitotic activity.
Papillary squamous cell carcinoma. This low-power image highlights the numerous delicate papillae seen with papillary squamous cell carcinoma.
Papillary squamous cell carcinoma. At higher magnification, the papillae are covered by a malignant stratified squamous epithelium.
A: malignant stratified squamous epithelium
Back Extra: Papillary Squamous Cell Carcinoma
- Clinical: Patients with Papillary Squamous Cell Carcinoma most often present with hoarseness, dysphagia, sore throat, cough, and haemoptysis, and are usually identified in or after the sixth decade of life.
- Micro: Papillary squamous cell carcinoma is characterized by numerous complex papillary and filiform structures covered with a malignant stratified squamous epithelium, with features such as lack of maturation, increased N:C ratios, and numerous mitotic figures.
- Ancillary: Typical block-like p16 expression is seen in Papillary Squamous Cell Carcinoma secondary to high-risk HPV, especially in the non-keratinizing type.
Reference Gallery:
Papillary squamous cell carcinoma. This low-power image highlights the numerous delicate papillae seen with papillary squamous cell carcinoma.
Papillary squamous cell carcinoma. At higher magnification, the papillae are covered by a malignant stratified squamous epithelium.
Papillary squamous cell carcinoma. Diffuse, block-like p16 expression is seen with this hypopharyngeal papillary squamous cell carcinoma that was secondary to high-risk HPV infection.

Q: When Papillary Squamous Cell Carcinoma is secondary to a high-risk HPV infection (especially the non-keratinizing type), immunohistochemical staining characteristically shows diffuse, block-like positivity for [...].
Papillary squamous cell carcinoma. Diffuse, block-like p16 expression is seen with this hypopharyngeal papillary squamous cell carcinoma that was secondary to high-risk HPV infection.
A: p16
Back Extra: Papillary Squamous Cell Carcinoma
- Clinical: Patients with Papillary Squamous Cell Carcinoma most often present with hoarseness, dysphagia, sore throat, cough, and haemoptysis, and are usually identified in or after the sixth decade of life.
- Micro: Papillary squamous cell carcinoma is characterized by numerous complex papillary and filiform structures covered with a malignant stratified squamous epithelium, with features such as lack of maturation, increased N:C ratios, and numerous mitotic figures.
- Ancillary: Typical block-like p16 expression is seen in Papillary Squamous Cell Carcinoma secondary to high-risk HPV, especially in the non-keratinizing type.
Reference Gallery:
Papillary squamous cell carcinoma. This low-power image highlights the numerous delicate papillae seen with papillary squamous cell carcinoma.
Papillary squamous cell carcinoma. At higher magnification, the papillae are covered by a malignant stratified squamous epithelium.
Papillary squamous cell carcinoma. Diffuse, block-like p16 expression is seen with this hypopharyngeal papillary squamous cell carcinoma that was secondary to high-risk HPV infection.

Q: Macroscopically, Spindle Cell Squamous Cell Carcinoma of the larynx classically presents as an exophytic, [...] tumor with a fleshy and hemorrhagic cut surface.
Spindle cell squamous cell carcinoma. Typical macroscopic appearance of laryngeal spindle cell squamous cell carcinoma showing a polypoid, bossed tumour of the glottis.
Spindle cell squamous cell carcinoma. The cut surface of spindle cell squamous cell carcinoma is fleshy and haemorrhagic.
A: polypoid
Back Extra: Spindle Cell Squamous Cell Carcinoma
- Clinical: Hoarseness is a common symptom, and a firm exophytic mass is often seen on laryngoscopy. Imaging is similar to conventional squamous cell carcinoma (SCC).
- Micro: Histological hallmark is spindle cell proliferation with pleomorphism, hyperchromasia, and increased mitotic activity. Patterns include fascicular, storiform, and cartwheel arrangements.
- Ancillary: Variable reactivity for cytokeratin, p63, and p40. Strongly positive for vimentin and may show weak SMA reactivity.
Reference Gallery:
Spindle cell squamous cell carcinoma. Associated with a well-differentiated squamous cell carcinoma.
Spindle cell squamous cell carcinoma. Associated with high-grade keratinizing dysplasia.
Spindle cell squamous cell carcinoma. Predominant fascicular growth pattern.
Spindle cell squamous cell carcinoma. Stellate cell morphology.
Spindle cell squamous cell carcinoma. Epithelioid pleomorphic cell morphology.
Spindle cell squamous cell carcinoma. Increased stromal collagenization.
Spindle cell squamous cell carcinoma. Diffuse and strong pancytokeratin reactivity.
Spindle cell squamous cell carcinoma. Focal pancytokeratin reactivity.
Spindle cell squamous cell carcinoma. Focal p63 reactivity.
Spindle cell squamous cell carcinoma. Weak SMA reactivity.
Spindle cell squamous cell carcinoma. Typical macroscopic appearance of laryngeal spindle cell squamous cell carcinoma showing a polypoid, bossed tumour of the glottis.
Spindle cell squamous cell carcinoma. The cut surface of spindle cell squamous cell carcinoma is fleshy and haemorrhagic.

Q: Microscopically, Spindle Cell Squamous Cell Carcinoma is characterized by a malignant spindle cell proliferation often exhibiting a prominent [...] or storiform growth pattern, which may arise adjacent to high-grade keratinizing dysplasia.
Spindle cell squamous cell carcinoma. Associated with high-grade keratinizing dysplasia.
Spindle cell squamous cell carcinoma. Predominant fascicular growth pattern.
A: fascicular
Back Extra: Spindle Cell Squamous Cell Carcinoma
- Clinical: Hoarseness is a common symptom, and a firm exophytic mass is often seen on laryngoscopy. Imaging is similar to conventional squamous cell carcinoma (SCC).
- Micro: Histological hallmark is spindle cell proliferation with pleomorphism, hyperchromasia, and increased mitotic activity. Patterns include fascicular, storiform, and cartwheel arrangements.
- Ancillary: Variable reactivity for cytokeratin, p63, and p40. Strongly positive for vimentin and may show weak SMA reactivity.
Reference Gallery:
Spindle cell squamous cell carcinoma. Associated with a well-differentiated squamous cell carcinoma.
Spindle cell squamous cell carcinoma. Associated with high-grade keratinizing dysplasia.
Spindle cell squamous cell carcinoma. Predominant fascicular growth pattern.
Spindle cell squamous cell carcinoma. Stellate cell morphology.
Spindle cell squamous cell carcinoma. Epithelioid pleomorphic cell morphology.
Spindle cell squamous cell carcinoma. Increased stromal collagenization.
Spindle cell squamous cell carcinoma. Diffuse and strong pancytokeratin reactivity.
Spindle cell squamous cell carcinoma. Focal pancytokeratin reactivity.
Spindle cell squamous cell carcinoma. Focal p63 reactivity.
Spindle cell squamous cell carcinoma. Weak SMA reactivity.
Spindle cell squamous cell carcinoma. Typical macroscopic appearance of laryngeal spindle cell squamous cell carcinoma showing a polypoid, bossed tumour of the glottis.
Spindle cell squamous cell carcinoma. The cut surface of spindle cell squamous cell carcinoma is fleshy and haemorrhagic.

Q: In Spindle Cell Squamous Cell Carcinoma, the spindle cell component strongly expresses vimentin but characteristically shows only variable or focal reactivity for squamous markers such as p63 and [...].
Spindle cell squamous cell carcinoma. Focal pancytokeratin reactivity.
Spindle cell squamous cell carcinoma. Focal p63 reactivity.
A: pancytokeratin
Back Extra: Spindle Cell Squamous Cell Carcinoma
- Clinical: Hoarseness is a common symptom, and a firm exophytic mass is often seen on laryngoscopy. Imaging is similar to conventional squamous cell carcinoma (SCC).
- Micro: Histological hallmark is spindle cell proliferation with pleomorphism, hyperchromasia, and increased mitotic activity. Patterns include fascicular, storiform, and cartwheel arrangements.
- Ancillary: Variable reactivity for cytokeratin, p63, and p40. Strongly positive for vimentin and may show weak SMA reactivity.
Reference Gallery:
Spindle cell squamous cell carcinoma. Associated with a well-differentiated squamous cell carcinoma.
Spindle cell squamous cell carcinoma. Associated with high-grade keratinizing dysplasia.
Spindle cell squamous cell carcinoma. Predominant fascicular growth pattern.
Spindle cell squamous cell carcinoma. Stellate cell morphology.
Spindle cell squamous cell carcinoma. Epithelioid pleomorphic cell morphology.
Spindle cell squamous cell carcinoma. Increased stromal collagenization.
Spindle cell squamous cell carcinoma. Diffuse and strong pancytokeratin reactivity.
Spindle cell squamous cell carcinoma. Focal pancytokeratin reactivity.
Spindle cell squamous cell carcinoma. Focal p63 reactivity.
Spindle cell squamous cell carcinoma. Weak SMA reactivity.
Spindle cell squamous cell carcinoma. Typical macroscopic appearance of laryngeal spindle cell squamous cell carcinoma showing a polypoid, bossed tumour of the glottis.
Spindle cell squamous cell carcinoma. The cut surface of spindle cell squamous cell carcinoma is fleshy and haemorrhagic.

Q: Verrucous carcinoma is histologically characterized by thickened, undulating projections of well-differentiated squamous epithelium that invade the stroma with broad, [...] borders rather than infiltrative nests.
Verrucous carcinoma. Verrucous carcinoma of the larynx. Invasion takes the form of expanded epithelium, which pushes into the stroma in rounded nests that have abundant glassy cytoplasm, round nuclei with prominent nucleoli, and little mitotic activity. There is no stromal reaction.
Verrucous carcinoma. Thickened, undulating projections and invaginations of well-differentiated squamous epithelium with marked surface keratinization. The invasive area has well-defined pushing borders extending below the level of the surrounding epithelium.
Verrucous carcinoma. Invaginations and pushing projections of well-differentiated squamous epithelium with one layer of basal cells. The surrounding stroma is densely infiltrated by lymphocytes.
A: pushing
Back Extra: Verrucous Carcinoma
- Clinical: Verrucous Carcinoma (VC) most commonly presents with hoarseness (90%) and dyspnoea (10%).
- Micro: Classic VC is characterized by thickened, undulating projections of well-differentiated squamous epithelium with glassy eosinophilic cytoplasm and marked surface keratinization.
- Ancillary: Ancillary studies are not relevant in diagnosing Verrucous Carcinoma.
Reference Gallery:
Verrucous carcinoma of the larynx. A large verrucous carcinoma of the true cords from a laryngectomy specimen showing a granular, tan, exophytic mass.
Verrucous carcinoma. Verrucous carcinoma of the larynx. Invasion takes the form of expanded epithelium, which pushes into the stroma in rounded nests that have abundant glassy cytoplasm, round nuclei with prominent nucleoli, and little mitotic activity. There is no stromal reaction.
Verrucous carcinoma. Verrucous carcinoma with stromally invasive conventional squamous cell carcinoma (or hybrid verrucous carcinoma). The tumour shows a large, maturing verrucous component (above) and small, infiltrative, invasive nests (below).
Verrucous carcinoma. Thickened, undulating projections and invaginations of well-differentiated squamous epithelium with marked surface keratinization. The invasive area has well-defined pushing borders extending below the level of the surrounding epithelium.
Verrucous carcinoma. Invaginations and pushing projections of well-differentiated squamous epithelium with one layer of basal cells. The surrounding stroma is densely infiltrated by lymphocytes.

Q: Verrucous carcinoma of the larynx most commonly presents clinically with hoarseness and grossly appears as a granular, tan, [...] mass.
Verrucous carcinoma of the larynx. A large verrucous carcinoma of the true cords from a laryngectomy specimen showing a granular, tan, exophytic mass.
A: exophytic
Back Extra: Verrucous Carcinoma
- Clinical: Verrucous Carcinoma (VC) most commonly presents with hoarseness (90%) and dyspnoea (10%).
- Micro: Classic VC is characterized by thickened, undulating projections of well-differentiated squamous epithelium with glassy eosinophilic cytoplasm and marked surface keratinization.
- Ancillary: Ancillary studies are not relevant in diagnosing Verrucous Carcinoma.
Reference Gallery:
Verrucous carcinoma of the larynx. A large verrucous carcinoma of the true cords from a laryngectomy specimen showing a granular, tan, exophytic mass.
Verrucous carcinoma. Verrucous carcinoma of the larynx. Invasion takes the form of expanded epithelium, which pushes into the stroma in rounded nests that have abundant glassy cytoplasm, round nuclei with prominent nucleoli, and little mitotic activity. There is no stromal reaction.
Verrucous carcinoma. Verrucous carcinoma with stromally invasive conventional squamous cell carcinoma (or hybrid verrucous carcinoma). The tumour shows a large, maturing verrucous component (above) and small, infiltrative, invasive nests (below).
Verrucous carcinoma. Thickened, undulating projections and invaginations of well-differentiated squamous epithelium with marked surface keratinization. The invasive area has well-defined pushing borders extending below the level of the surrounding epithelium.
Verrucous carcinoma. Invaginations and pushing projections of well-differentiated squamous epithelium with one layer of basal cells. The surrounding stroma is densely infiltrated by lymphocytes.

Q: Verrucous carcinoma that contains a concurrent, infiltrative component of conventional squamous cell carcinoma is classified as a [...] tumor.
Verrucous carcinoma. Verrucous carcinoma with stromally invasive conventional squamous cell carcinoma (or hybrid verrucous carcinoma). The tumour shows a large, maturing verrucous component (above) and small, infiltrative, invasive nests (below).
A: hybrid
Back Extra: Verrucous Carcinoma
- Clinical: Verrucous Carcinoma (VC) most commonly presents with hoarseness (90%) and dyspnoea (10%).
- Micro: Classic VC is characterized by thickened, undulating projections of well-differentiated squamous epithelium with glassy eosinophilic cytoplasm and marked surface keratinization.
- Ancillary: Ancillary studies are not relevant in diagnosing Verrucous Carcinoma.
Reference Gallery:
Verrucous carcinoma of the larynx. A large verrucous carcinoma of the true cords from a laryngectomy specimen showing a granular, tan, exophytic mass.
Verrucous carcinoma. Verrucous carcinoma of the larynx. Invasion takes the form of expanded epithelium, which pushes into the stroma in rounded nests that have abundant glassy cytoplasm, round nuclei with prominent nucleoli, and little mitotic activity. There is no stromal reaction.
Verrucous carcinoma. Verrucous carcinoma with stromally invasive conventional squamous cell carcinoma (or hybrid verrucous carcinoma). The tumour shows a large, maturing verrucous component (above) and small, infiltrative, invasive nests (below).
Verrucous carcinoma. Thickened, undulating projections and invaginations of well-differentiated squamous epithelium with marked surface keratinization. The invasive area has well-defined pushing borders extending below the level of the surrounding epithelium.
Verrucous carcinoma. Invaginations and pushing projections of well-differentiated squamous epithelium with one layer of basal cells. The surrounding stroma is densely infiltrated by lymphocytes.

Q: In a grade 1 Laryngeal Cartilaginous Tumor (chondrosarcoma), the microscopic examination typically reveals increased cellularity and characteristic [...] without significant cytologic atypia.
Laryngeal chondrosarcoma, grade 1. The tumour demonstrates increased cellularity, but no significant atypia. Cluster disarray is present.
Laryngeal chondroma. There is a slightly increased cellularity within normally spaced chondrocytes that do not show cluster disarray. These tumours are < 20 mm by definition, without destructive growth by imaging.
A: cluster disarray
Back Extra: Laryngeal Cartilaginous Tumor
- Clinical: Laryngeal cartilaginous tumors grow slowly, often presenting with symptoms such as hoarseness, dyspnea, and dysphagia due to the endolaryngeal mass.
- Micro: Grade 1 laryngeal chondrosarcomas exhibit increased cellularity with cluster disarray, while higher grades show significant pleomorphism, mitotic activity, and necrosis.
- Ancillary: Immunohistochemistry shows chondroid cells positive for S100, SOX9, and D2-40, and negative for keratin and EMA.
Reference Gallery:
Laryngeal chondrosarcoma. A macroscopic section of laryngeal chondrosarcoma showing extension of the translucent cartilaginous tumour into the adjacent soft tissues.
Laryngeal chondrosarcoma. A low-power image demonstrates islands of destructively invasive chondrocytes, expanding the bony trabeculae and extending into the perilaryngeal soft tissues.
Laryngeal chondrosarcoma. The posterior lamina of the cricoid cartilage is destroyed by a neoplasm with popcorn-type calcification (CT, axial plane).
Laryngeal chondrosarcoma, grade 1. Neoplastic cartilage is noted, destroying the spicules of bone. Note the normal cartilage (far left).
Laryngeal chondrosarcoma, grade 1. Ischaemic change (granular blue cytoplasmic degeneration) is noted in the adjacent chondroma (left), and chondrosarcoma is noted on the right.
Laryngeal chondrosarcoma, grade 1. Calcification and residual bone from the endochondral ossification of the laryngeal cartilages may be seen within the background of the chondrosarcoma.
Laryngeal chondrosarcoma, grade 1. The tumour demonstrates increased cellularity, but no significant atypia. Cluster disarray is present.
Laryngeal chondrosarcoma. Tumours are graded, with this tumour demonstrating significant cellularity, pleomorphism, mitoses, and tumour necrosis, moving the lesion to grade 3 of 3.
Laryngeal chondrosarcoma. Myxoid pattern of chondrosarcoma, demonstrating myxoid change around the chondrocytes.
Laryngeal chondrosarcoma. Mesenchymal chondrosarcoma demonstrates a malignant spindled cell component immediately adjacent to islands of cartilaginous differentiation.
Laryngeal chondroma. There is a slightly increased cellularity within normally spaced chondrocytes that do not show cluster disarray. These tumours are < 20 mm by definition, without destructive growth by imaging.
Laryngeal chondrosarcoma. There is increased cellularity, with nuclear pleomorphism easily identified in this grade 2 chondrosarcoma.

Q: On computed tomography (CT), a malignant Laryngeal Cartilaginous Tumor commonly destroys the underlying cartilage (often the cricoid) and exhibits characteristic [...]-type calcification.
Laryngeal chondrosarcoma. The posterior lamina of the cricoid cartilage is destroyed by a neoplasm with popcorn-type calcification (CT, axial plane).
A: popcorn
Back Extra: Laryngeal Cartilaginous Tumor
- Clinical: Laryngeal cartilaginous tumors grow slowly, often presenting with symptoms such as hoarseness, dyspnea, and dysphagia due to the endolaryngeal mass.
- Micro: Grade 1 laryngeal chondrosarcomas exhibit increased cellularity with cluster disarray, while higher grades show significant pleomorphism, mitotic activity, and necrosis.
- Ancillary: Immunohistochemistry shows chondroid cells positive for S100, SOX9, and D2-40, and negative for keratin and EMA.
Reference Gallery:
Laryngeal chondrosarcoma. A macroscopic section of laryngeal chondrosarcoma showing extension of the translucent cartilaginous tumour into the adjacent soft tissues.
Laryngeal chondrosarcoma. A low-power image demonstrates islands of destructively invasive chondrocytes, expanding the bony trabeculae and extending into the perilaryngeal soft tissues.
Laryngeal chondrosarcoma. The posterior lamina of the cricoid cartilage is destroyed by a neoplasm with popcorn-type calcification (CT, axial plane).
Laryngeal chondrosarcoma, grade 1. Neoplastic cartilage is noted, destroying the spicules of bone. Note the normal cartilage (far left).
Laryngeal chondrosarcoma, grade 1. Ischaemic change (granular blue cytoplasmic degeneration) is noted in the adjacent chondroma (left), and chondrosarcoma is noted on the right.
Laryngeal chondrosarcoma, grade 1. Calcification and residual bone from the endochondral ossification of the laryngeal cartilages may be seen within the background of the chondrosarcoma.
Laryngeal chondrosarcoma, grade 1. The tumour demonstrates increased cellularity, but no significant atypia. Cluster disarray is present.
Laryngeal chondrosarcoma. Tumours are graded, with this tumour demonstrating significant cellularity, pleomorphism, mitoses, and tumour necrosis, moving the lesion to grade 3 of 3.
Laryngeal chondrosarcoma. Myxoid pattern of chondrosarcoma, demonstrating myxoid change around the chondrocytes.
Laryngeal chondrosarcoma. Mesenchymal chondrosarcoma demonstrates a malignant spindled cell component immediately adjacent to islands of cartilaginous differentiation.
Laryngeal chondroma. There is a slightly increased cellularity within normally spaced chondrocytes that do not show cluster disarray. These tumours are < 20 mm by definition, without destructive growth by imaging.
Laryngeal chondrosarcoma. There is increased cellularity, with nuclear pleomorphism easily identified in this grade 2 chondrosarcoma.

Q: While a low-grade Laryngeal Cartilaginous Tumor appears relatively well-differentiated, progression to a grade 3 tumor is defined by significant cellularity, marked pleomorphism, increased mitoses, and the presence of [...].
Laryngeal chondrosarcoma. Tumours are graded, with this tumour demonstrating significant cellularity, pleomorphism, mitoses, and tumour necrosis, moving the lesion to grade 3 of 3.
A: tumor necrosis
Back Extra: Laryngeal Cartilaginous Tumor
- Clinical: Laryngeal cartilaginous tumors grow slowly, often presenting with symptoms such as hoarseness, dyspnea, and dysphagia due to the endolaryngeal mass.
- Micro: Grade 1 laryngeal chondrosarcomas exhibit increased cellularity with cluster disarray, while higher grades show significant pleomorphism, mitotic activity, and necrosis.
- Ancillary: Immunohistochemistry shows chondroid cells positive for S100, SOX9, and D2-40, and negative for keratin and EMA.
Reference Gallery:
Laryngeal chondrosarcoma. A macroscopic section of laryngeal chondrosarcoma showing extension of the translucent cartilaginous tumour into the adjacent soft tissues.
Laryngeal chondrosarcoma. A low-power image demonstrates islands of destructively invasive chondrocytes, expanding the bony trabeculae and extending into the perilaryngeal soft tissues.
Laryngeal chondrosarcoma. The posterior lamina of the cricoid cartilage is destroyed by a neoplasm with popcorn-type calcification (CT, axial plane).
Laryngeal chondrosarcoma, grade 1. Neoplastic cartilage is noted, destroying the spicules of bone. Note the normal cartilage (far left).
Laryngeal chondrosarcoma, grade 1. Ischaemic change (granular blue cytoplasmic degeneration) is noted in the adjacent chondroma (left), and chondrosarcoma is noted on the right.
Laryngeal chondrosarcoma, grade 1. Calcification and residual bone from the endochondral ossification of the laryngeal cartilages may be seen within the background of the chondrosarcoma.
Laryngeal chondrosarcoma, grade 1. The tumour demonstrates increased cellularity, but no significant atypia. Cluster disarray is present.
Laryngeal chondrosarcoma. Tumours are graded, with this tumour demonstrating significant cellularity, pleomorphism, mitoses, and tumour necrosis, moving the lesion to grade 3 of 3.
Laryngeal chondrosarcoma. Myxoid pattern of chondrosarcoma, demonstrating myxoid change around the chondrocytes.
Laryngeal chondrosarcoma. Mesenchymal chondrosarcoma demonstrates a malignant spindled cell component immediately adjacent to islands of cartilaginous differentiation.
Laryngeal chondroma. There is a slightly increased cellularity within normally spaced chondrocytes that do not show cluster disarray. These tumours are < 20 mm by definition, without destructive growth by imaging.
Laryngeal chondrosarcoma. There is increased cellularity, with nuclear pleomorphism easily identified in this grade 2 chondrosarcoma.

Q: Severe architectural disorganization with full-thickness cellular atypia, complete loss of stratification, and an intact basement membrane is characteristic of carcinoma in situ in [...].
Laryngeal and hypopharyngeal epithelial dysplasia. Carcinoma in situ. There is prominent architectural disorganization, with complete loss of stratification and polarity. Severe cellular and nuclear atypia, mitoses, and apoptotic cells are seen in the entire thickness of the epithelium. The basement membrane is preserved.
Laryngeal epithelial dysplasia, carcinoma in situ. Laryngeal mucosa showing marked cytological atypia in keeping with carcinoma in situ. The basement membrane is intact.
A: Laryngeal and Hypopharyngeal Epithelial Dysplasia
Back Extra: Laryngeal and Hypopharyngeal Epithelial Dysplasia
- Clinical: Laryngeal and hypopharyngeal epithelial dysplasia is often asymptomatic, but symptoms like voice change and hoarseness can occur in the glottis.
- Micro: High-grade dysplasia shows marked cellular and nuclear atypia, loss of stratification, and a preserved basement membrane.
- Ancillary: NANOG expression can help differentiate between low-grade and high-grade dysplasia, with strong expression seen in high-grade dysplasia, carcinoma in situ, and squamous cell carcinoma.
Reference Gallery:
Laryngeal and hypopharyngeal epithelial dysplasia, low-grade. Augmented basal and parabasal cells, occupying the lower half of the epithelial thickness.
Laryngeal and hypopharyngeal epithelial dysplasia. High-grade dysplasia of the basaloid subtype with no maturation. Augmented basaloid cells with marked cellular and nuclear atypia occupy almost the entire thickness of the epithelium.
Laryngeal and hypopharyngeal epithelial dysplasia. High-grade dysplasia of the large, spinous cell type, with maturation. Augmented basaloid and spinous cells with marked cellular and nuclear atypia occupy almost the entire thickness of the epithelium.
Laryngeal and hypopharyngeal epithelial dysplasia. Carcinoma in situ. There is prominent architectural disorganization, with complete loss of stratification and polarity. Severe cellular and nuclear atypia, mitoses, and apoptotic cells are seen in the entire thickness of the epithelium. The basement membrane is preserved.
Laryngeal epithelial dysplasia, high-grade. Laryngeal mucosa showing detail of cytological changes in high-grade dysplasia.
Laryngeal epithelial dysplasia, carcinoma in situ. Laryngeal mucosa showing marked cytological atypia in keeping with carcinoma in situ. The basement membrane is intact.
Laryngeal epithelial dysplasia, low-grade. Laryngeal mucosa showing architectural disorganization and nuclear hyperchromasia in the lower third of the epithelium, typical of low-grade dysplasia.
Laryngeal epithelial dysplasia. Laryngoscopic appearance of leukoplakia and squamous cell carcinoma. Endoscopy with white light. The right vocal cord (arrow) is erythematous, with a small focus of leukoplakia anteriorly. The left vocal cord shows exophytic carcinoma of the anterior third infiltrating the sinus of Morgagni and anterior commissure.

Q: Augmented basal and parabasal cells with architectural disorganization restricted to the lower third to half of the epithelium is the hallmark of the low-grade form of [...].
Laryngeal and hypopharyngeal epithelial dysplasia, low-grade. Augmented basal and parabasal cells, occupying the lower half of the epithelial thickness.
Laryngeal epithelial dysplasia, low-grade. Laryngeal mucosa showing architectural disorganization and nuclear hyperchromasia in the lower third of the epithelium, typical of low-grade dysplasia.
A: Laryngeal and Hypopharyngeal Epithelial Dysplasia
Back Extra: Laryngeal and Hypopharyngeal Epithelial Dysplasia
- Clinical: Laryngeal and hypopharyngeal epithelial dysplasia is often asymptomatic, but symptoms like voice change and hoarseness can occur in the glottis.
- Micro: High-grade dysplasia shows marked cellular and nuclear atypia, loss of stratification, and a preserved basement membrane.
- Ancillary: NANOG expression can help differentiate between low-grade and high-grade dysplasia, with strong expression seen in high-grade dysplasia, carcinoma in situ, and squamous cell carcinoma.
Reference Gallery:
Laryngeal and hypopharyngeal epithelial dysplasia, low-grade. Augmented basal and parabasal cells, occupying the lower half of the epithelial thickness.
Laryngeal and hypopharyngeal epithelial dysplasia. High-grade dysplasia of the basaloid subtype with no maturation. Augmented basaloid cells with marked cellular and nuclear atypia occupy almost the entire thickness of the epithelium.
Laryngeal and hypopharyngeal epithelial dysplasia. High-grade dysplasia of the large, spinous cell type, with maturation. Augmented basaloid and spinous cells with marked cellular and nuclear atypia occupy almost the entire thickness of the epithelium.
Laryngeal and hypopharyngeal epithelial dysplasia. Carcinoma in situ. There is prominent architectural disorganization, with complete loss of stratification and polarity. Severe cellular and nuclear atypia, mitoses, and apoptotic cells are seen in the entire thickness of the epithelium. The basement membrane is preserved.
Laryngeal epithelial dysplasia, high-grade. Laryngeal mucosa showing detail of cytological changes in high-grade dysplasia.
Laryngeal epithelial dysplasia, carcinoma in situ. Laryngeal mucosa showing marked cytological atypia in keeping with carcinoma in situ. The basement membrane is intact.
Laryngeal epithelial dysplasia, low-grade. Laryngeal mucosa showing architectural disorganization and nuclear hyperchromasia in the lower third of the epithelium, typical of low-grade dysplasia.
Laryngeal epithelial dysplasia. Laryngoscopic appearance of leukoplakia and squamous cell carcinoma. Endoscopy with white light. The right vocal cord (arrow) is erythematous, with a small focus of leukoplakia anteriorly. The left vocal cord shows exophytic carcinoma of the anterior third infiltrating the sinus of Morgagni and anterior commissure.

Q: While often asymptomatic, Laryngeal and Hypopharyngeal Epithelial Dysplasia affecting the glottis can present with voice changes and frequently appears on laryngoscopy as a white mucosal patch termed [...].
Laryngeal epithelial dysplasia. Laryngoscopic appearance of leukoplakia and squamous cell carcinoma. Endoscopy with white light. The right vocal cord (arrow) is erythematous, with a small focus of leukoplakia anteriorly. The left vocal cord shows exophytic carcinoma of the anterior third infiltrating the sinus of Morgagni and anterior commissure.
A: leukoplakia
Back Extra: Laryngeal and Hypopharyngeal Epithelial Dysplasia
- Clinical: Laryngeal and hypopharyngeal epithelial dysplasia is often asymptomatic, but symptoms like voice change and hoarseness can occur in the glottis.
- Micro: High-grade dysplasia shows marked cellular and nuclear atypia, loss of stratification, and a preserved basement membrane.
- Ancillary: NANOG expression can help differentiate between low-grade and high-grade dysplasia, with strong expression seen in high-grade dysplasia, carcinoma in situ, and squamous cell carcinoma.
Reference Gallery:
Laryngeal and hypopharyngeal epithelial dysplasia, low-grade. Augmented basal and parabasal cells, occupying the lower half of the epithelial thickness.
Laryngeal and hypopharyngeal epithelial dysplasia. High-grade dysplasia of the basaloid subtype with no maturation. Augmented basaloid cells with marked cellular and nuclear atypia occupy almost the entire thickness of the epithelium.
Laryngeal and hypopharyngeal epithelial dysplasia. High-grade dysplasia of the large, spinous cell type, with maturation. Augmented basaloid and spinous cells with marked cellular and nuclear atypia occupy almost the entire thickness of the epithelium.
Laryngeal and hypopharyngeal epithelial dysplasia. Carcinoma in situ. There is prominent architectural disorganization, with complete loss of stratification and polarity. Severe cellular and nuclear atypia, mitoses, and apoptotic cells are seen in the entire thickness of the epithelium. The basement membrane is preserved.
Laryngeal epithelial dysplasia, high-grade. Laryngeal mucosa showing detail of cytological changes in high-grade dysplasia.
Laryngeal epithelial dysplasia, carcinoma in situ. Laryngeal mucosa showing marked cytological atypia in keeping with carcinoma in situ. The basement membrane is intact.
Laryngeal epithelial dysplasia, low-grade. Laryngeal mucosa showing architectural disorganization and nuclear hyperchromasia in the lower third of the epithelium, typical of low-grade dysplasia.
Laryngeal epithelial dysplasia. Laryngoscopic appearance of leukoplakia and squamous cell carcinoma. Endoscopy with white light. The right vocal cord (arrow) is erythematous, with a small focus of leukoplakia anteriorly. The left vocal cord shows exophytic carcinoma of the anterior third infiltrating the sinus of Morgagni and anterior commissure.

Q: Clinically, a Squamous Papilloma classically presents as a solitary, white, pedunculated or sessile lesion with a characteristic [...] or finger-like surface.
Squamous papilloma. Ventral tongue squamous papilloma presenting as a solitary, white, somewhat sessile lesion with finger-like fronds.
A: cauliflower-like
Back Extra: Squamous Papilloma
- Clinical: Most squamous papillomas are < 10 mm, pedunculated, and white, with a cauliflower-like or finger-like surface.
- Micro: Squamous papillomas show exophytic papillary proliferation of hyperplastic stratified squamous epithelium with a thin, branching core of fibrovascular connective tissue.
- Ancillary: Essential features include exophytic, pedunculated or sessile papillary architecture, epithelial hyperplasia, and parakeratosis/orthokeratosis.
Reference Gallery:
Squamous papilloma. Exophytic, pedunculated, papillary lesion consisting of a thin, branching core of fibrovascular connective tissue covered by hyperplastic stratified squamous parakeratinized epithelium.
Squamous papilloma. Papillary projections covered by stratified squamous parakeratinized epithelium with basal cell hyperplasia and orderly maturation.
Squamous papilloma. Lacking exophytic papillary projections, sessile papillomas have blunted, rounded papillae. Koilocytes generally are absent. The architecture may be a reflection of frictional forces in the oral cavity.
Squamous papilloma. Ventral tongue squamous papilloma presenting as a solitary, white, somewhat sessile lesion with finger-like fronds.

Q: Microscopically, a Squamous Papilloma is characterized by an exophytic proliferation of hyperplastic stratified squamous epithelium supported by a thin, branching [...].
Squamous papilloma. Exophytic, pedunculated, papillary lesion consisting of a thin, branching core of fibrovascular connective tissue covered by hyperplastic stratified squamous parakeratinized epithelium.
Squamous papilloma. Papillary projections covered by stratified squamous parakeratinized epithelium with basal cell hyperplasia and orderly maturation.
A: fibrovascular core
Back Extra: Squamous Papilloma
- Clinical: Most squamous papillomas are < 10 mm, pedunculated, and white, with a cauliflower-like or finger-like surface.
- Micro: Squamous papillomas show exophytic papillary proliferation of hyperplastic stratified squamous epithelium with a thin, branching core of fibrovascular connective tissue.
- Ancillary: Essential features include exophytic, pedunculated or sessile papillary architecture, epithelial hyperplasia, and parakeratosis/orthokeratosis.
Reference Gallery:
Squamous papilloma. Exophytic, pedunculated, papillary lesion consisting of a thin, branching core of fibrovascular connective tissue covered by hyperplastic stratified squamous parakeratinized epithelium.
Squamous papilloma. Papillary projections covered by stratified squamous parakeratinized epithelium with basal cell hyperplasia and orderly maturation.
Squamous papilloma. Lacking exophytic papillary projections, sessile papillomas have blunted, rounded papillae. Koilocytes generally are absent. The architecture may be a reflection of frictional forces in the oral cavity.
Squamous papilloma. Ventral tongue squamous papilloma presenting as a solitary, white, somewhat sessile lesion with finger-like fronds.

Q: In contrast to some other HPV-mediated mucosal lesions, histology of a typical Squamous Papilloma generally lacks classic viral cytopathic changes, meaning [...] are characteristically absent.
Squamous papilloma. Lacking exophytic papillary projections, sessile papillomas have blunted, rounded papillae. Koilocytes generally are absent. The architecture may be a reflection of frictional forces in the oral cavity.
A: koilocytes
Back Extra: Squamous Papilloma
- Clinical: Most squamous papillomas are < 10 mm, pedunculated, and white, with a cauliflower-like or finger-like surface.
- Micro: Squamous papillomas show exophytic papillary proliferation of hyperplastic stratified squamous epithelium with a thin, branching core of fibrovascular connective tissue.
- Ancillary: Essential features include exophytic, pedunculated or sessile papillary architecture, epithelial hyperplasia, and parakeratosis/orthokeratosis.
Reference Gallery:
Squamous papilloma. Exophytic, pedunculated, papillary lesion consisting of a thin, branching core of fibrovascular connective tissue covered by hyperplastic stratified squamous parakeratinized epithelium.
Squamous papilloma. Papillary projections covered by stratified squamous parakeratinized epithelium with basal cell hyperplasia and orderly maturation.
Squamous papilloma. Lacking exophytic papillary projections, sessile papillomas have blunted, rounded papillae. Koilocytes generally are absent. The architecture may be a reflection of frictional forces in the oral cavity.
Squamous papilloma. Ventral tongue squamous papilloma presenting as a solitary, white, somewhat sessile lesion with finger-like fronds.

Q: In Squamous Papilloma and Papillomatosis, gross and laryngoscopic examination typically reveals sessile, [...]-like masses covering the vocal cords, which can cause progressive hoarseness.
Squamous papillomatosis, larynx. Friable papillomas line the endolarynx.
Squamous papilloma, laryngoscopic appearance. Sessile, cauliflower-like masses cover almost two thirds of the right vocal cord and the anterior third of the left vocal cord.
A: cauliflower
Back Extra: Squamous Papilloma and Papillomatosis
- Clinical: Squamous Papilloma and Papillomatosis commonly presents with progressive hoarseness, stridor, and obstructive airway symptoms, especially in children under 5 years and adults aged 20–40 years.
- Micro: Squamous papillomas have a complex, thin fibrovascular core covered by hyperplastic squamous epithelium with koilocytic changes and minimal surface keratinization.
- Ancillary: In situ hybridization is positive for episomal HPV6 and HPV11 in the upper layers of the squamous epithelial lining.
Reference Gallery:
Squamous cell papillomatosis. Note the high-grade squamous dysplasia present within the surface epithelium of this papillary branch. HPV11 was present.
Squamous papillomatosis, larynx. Friable papillomas line the endolarynx.
Squamous cell papilloma of the larynx. High-magnification view of a papilloma branch with pronounced koilocytosis.
Squamous cell papillomas of the larynx. Positive diffuse in situ hybridization signal for episomal HPV6 and HPV11 within the upper layers of the squamous epithelial lining.
Squamous papilloma, laryngoscopic appearance. Sessile, cauliflower-like masses cover almost two thirds of the right vocal cord and the anterior third of the left vocal cord.

Q: The characteristic histologic finding in Squamous Papilloma and Papillomatosis is a complex, thin fibrovascular core covered by hyperplastic squamous epithelium exhibiting pronounced [...].
Squamous cell papilloma of the larynx. High-magnification view of a papilloma branch with pronounced koilocytosis.
A: koilocytosis
Back Extra: Squamous Papilloma and Papillomatosis
- Clinical: Squamous Papilloma and Papillomatosis commonly presents with progressive hoarseness, stridor, and obstructive airway symptoms, especially in children under 5 years and adults aged 20–40 years.
- Micro: Squamous papillomas have a complex, thin fibrovascular core covered by hyperplastic squamous epithelium with koilocytic changes and minimal surface keratinization.
- Ancillary: In situ hybridization is positive for episomal HPV6 and HPV11 in the upper layers of the squamous epithelial lining.
Reference Gallery:
Squamous cell papillomatosis. Note the high-grade squamous dysplasia present within the surface epithelium of this papillary branch. HPV11 was present.
Squamous papillomatosis, larynx. Friable papillomas line the endolarynx.
Squamous cell papilloma of the larynx. High-magnification view of a papilloma branch with pronounced koilocytosis.
Squamous cell papillomas of the larynx. Positive diffuse in situ hybridization signal for episomal HPV6 and HPV11 within the upper layers of the squamous epithelial lining.
Squamous papilloma, laryngoscopic appearance. Sessile, cauliflower-like masses cover almost two thirds of the right vocal cord and the anterior third of the left vocal cord.

Q: In Squamous Papilloma and Papillomatosis, in situ hybridization is characteristically positive for episomal [...] within the upper layers of the squamous epithelial lining.
Squamous cell papillomas of the larynx. Positive diffuse in situ hybridization signal for episomal HPV6 and HPV11 within the upper layers of the squamous epithelial lining.
A: HPV6 and HPV11
Back Extra: Squamous Papilloma and Papillomatosis
- Clinical: Squamous Papilloma and Papillomatosis commonly presents with progressive hoarseness, stridor, and obstructive airway symptoms, especially in children under 5 years and adults aged 20–40 years.
- Micro: Squamous papillomas have a complex, thin fibrovascular core covered by hyperplastic squamous epithelium with koilocytic changes and minimal surface keratinization.
- Ancillary: In situ hybridization is positive for episomal HPV6 and HPV11 in the upper layers of the squamous epithelial lining.
Reference Gallery:
Squamous cell papillomatosis. Note the high-grade squamous dysplasia present within the surface epithelium of this papillary branch. HPV11 was present.
Squamous papillomatosis, larynx. Friable papillomas line the endolarynx.
Squamous cell papilloma of the larynx. High-magnification view of a papilloma branch with pronounced koilocytosis.
Squamous cell papillomas of the larynx. Positive diffuse in situ hybridization signal for episomal HPV6 and HPV11 within the upper layers of the squamous epithelial lining.
Squamous papilloma, laryngoscopic appearance. Sessile, cauliflower-like masses cover almost two thirds of the right vocal cord and the anterior third of the left vocal cord.

Q: In Mucosal Melanoma, amelanotic variants require immunohistochemistry for diagnosis, typically showing robust expression of melanocytic markers such as S100, HMB45, and [...].
Oral mucosal melanoma. The melanoma cells are highlighted by HMB45 immunohistochemistry.
Sinonasal mucosal melanoma. Immunohistochemistry for SOX10 highlights single and clustered intraepithelial malignant melanocytes.
Sinonasal mucosal melanoma. Amelanotic melanoma can mimic other sinonasal tumours and requires a panel of immunomarkers, including multiple melanoma markers, which can have variable sensitivity.
A: SOX10
Back Extra: Mucosal Melanoma
- Clinical: Sinonasal mucosal melanoma often presents with nonspecific symptoms such as nasal obstruction, sinus congestion, rhinorrhoea, and epistaxis.
- Micro: Mucosal melanoma cells are polymorphic, displaying spindled, epithelioid, plasmacytoid, or rhabdoid morphology, often within the same tumour.
- Ancillary: Immunohistochemistry is essential for diagnosing amelanotic mucosal melanomas, with robust expression of S100, HMB45, and SOX10 in epithelioid/undifferentiated cells.
Reference Gallery:
Sinonasal mucosal melanoma. Postcontrast MRI demonstrates a large sinonasal mucosal melanoma involving the nasal cavity and the maxillary, ethmoid, frontal, and sphenoid sinuses, with orbital and intracranial (extradural) extension.
Sinonasal mucosal melanoma. The tumour presents as a pigmented nodule in the nasal cavity.
Oral mucosal melanoma. Epithelioid tumour cells infiltrating the basal layer of squamous epithelium as single cells and the subepithelial tissue as nests. Melanin is noted.
Sinonasal mucosal melanoma. A variety of histological patterns can occur, including the peritheliomatous pattern comprising discohesive small blue round cells around blood vessels.
Sinonasal mucosal melanoma. Epithelioid tumour cells with amphophilic cytoplasm, large nuclei, and prominent nucleoli are arranged in solid sheets. Melanin is present.
Sinonasal mucosal melanoma. Spindled tumour cells are arranged in intersecting fascicles.
Oral mucosal melanoma. A tumour involving the hard palate, edentulous maxillary alveolar ridge, and buccal mucosa. The pigmented lesion exhibits irregular borders and prominent colour variation.
Oral mucosal melanoma. There is a radial growth phase similar to that in lentiginous melanoma, with atypical pigmented melanocytes in the basal layer spreading laterally and with vertical pagetoid spread, as well as invasive melanocytes in the stroma.
Oral mucosal melanoma. The melanoma cells are highlighted by HMB45 immunohistochemistry.
Sinonasal melanoma. Respiratory epithelium adjacent to tumour shows intraepithelial malignant melanocytes in clusters and as single cells.
Sinonasal mucosal melanoma. Immunohistochemistry for SOX10 highlights single and clustered intraepithelial malignant melanocytes.
Sinonasal mucosal melanoma. Amelanotic melanoma can mimic other sinonasal tumours and requires a panel of immunomarkers, including multiple melanoma markers, which can have variable sensitivity.

Q: Histologically, [...] is characterized by highly polymorphic tumor cells (epithelioid, spindled, plasmacytoid, or rhabdoid) that can form subepithelial nests or intersecting fascicles.
Oral mucosal melanoma. Epithelioid tumour cells infiltrating the basal layer of squamous epithelium as single cells and the subepithelial tissue as nests. Melanin is noted.
Sinonasal mucosal melanoma. Epithelioid tumour cells with amphophilic cytoplasm, large nuclei, and prominent nucleoli are arranged in solid sheets. Melanin is present.
Sinonasal mucosal melanoma. Spindled tumour cells are arranged in intersecting fascicles.
A: Mucosal Melanoma
Back Extra: Mucosal Melanoma
- Clinical: Sinonasal mucosal melanoma often presents with nonspecific symptoms such as nasal obstruction, sinus congestion, rhinorrhoea, and epistaxis.
- Micro: Mucosal melanoma cells are polymorphic, displaying spindled, epithelioid, plasmacytoid, or rhabdoid morphology, often within the same tumour.
- Ancillary: Immunohistochemistry is essential for diagnosing amelanotic mucosal melanomas, with robust expression of S100, HMB45, and SOX10 in epithelioid/undifferentiated cells.
Reference Gallery:
Sinonasal mucosal melanoma. Postcontrast MRI demonstrates a large sinonasal mucosal melanoma involving the nasal cavity and the maxillary, ethmoid, frontal, and sphenoid sinuses, with orbital and intracranial (extradural) extension.
Sinonasal mucosal melanoma. The tumour presents as a pigmented nodule in the nasal cavity.
Oral mucosal melanoma. Epithelioid tumour cells infiltrating the basal layer of squamous epithelium as single cells and the subepithelial tissue as nests. Melanin is noted.
Sinonasal mucosal melanoma. A variety of histological patterns can occur, including the peritheliomatous pattern comprising discohesive small blue round cells around blood vessels.
Sinonasal mucosal melanoma. Epithelioid tumour cells with amphophilic cytoplasm, large nuclei, and prominent nucleoli are arranged in solid sheets. Melanin is present.
Sinonasal mucosal melanoma. Spindled tumour cells are arranged in intersecting fascicles.
Oral mucosal melanoma. A tumour involving the hard palate, edentulous maxillary alveolar ridge, and buccal mucosa. The pigmented lesion exhibits irregular borders and prominent colour variation.
Oral mucosal melanoma. There is a radial growth phase similar to that in lentiginous melanoma, with atypical pigmented melanocytes in the basal layer spreading laterally and with vertical pagetoid spread, as well as invasive melanocytes in the stroma.
Oral mucosal melanoma. The melanoma cells are highlighted by HMB45 immunohistochemistry.
Sinonasal melanoma. Respiratory epithelium adjacent to tumour shows intraepithelial malignant melanocytes in clusters and as single cells.
Sinonasal mucosal melanoma. Immunohistochemistry for SOX10 highlights single and clustered intraepithelial malignant melanocytes.
Sinonasal mucosal melanoma. Amelanotic melanoma can mimic other sinonasal tumours and requires a panel of immunomarkers, including multiple melanoma markers, which can have variable sensitivity.

Q: The radial growth phase of Mucosal Melanoma often demonstrates intraepithelial malignant melanocytes with characteristic upward [...].
Oral mucosal melanoma. There is a radial growth phase similar to that in lentiginous melanoma, with atypical pigmented melanocytes in the basal layer spreading laterally and with vertical pagetoid spread, as well as invasive melanocytes in the stroma.
Sinonasal melanoma. Respiratory epithelium adjacent to tumour shows intraepithelial malignant melanocytes in clusters and as single cells.
A: pagetoid spread
Back Extra: Mucosal Melanoma
- Clinical: Sinonasal mucosal melanoma often presents with nonspecific symptoms such as nasal obstruction, sinus congestion, rhinorrhoea, and epistaxis.
- Micro: Mucosal melanoma cells are polymorphic, displaying spindled, epithelioid, plasmacytoid, or rhabdoid morphology, often within the same tumour.
- Ancillary: Immunohistochemistry is essential for diagnosing amelanotic mucosal melanomas, with robust expression of S100, HMB45, and SOX10 in epithelioid/undifferentiated cells.
Reference Gallery:
Sinonasal mucosal melanoma. Postcontrast MRI demonstrates a large sinonasal mucosal melanoma involving the nasal cavity and the maxillary, ethmoid, frontal, and sphenoid sinuses, with orbital and intracranial (extradural) extension.
Sinonasal mucosal melanoma. The tumour presents as a pigmented nodule in the nasal cavity.
Oral mucosal melanoma. Epithelioid tumour cells infiltrating the basal layer of squamous epithelium as single cells and the subepithelial tissue as nests. Melanin is noted.
Sinonasal mucosal melanoma. A variety of histological patterns can occur, including the peritheliomatous pattern comprising discohesive small blue round cells around blood vessels.
Sinonasal mucosal melanoma. Epithelioid tumour cells with amphophilic cytoplasm, large nuclei, and prominent nucleoli are arranged in solid sheets. Melanin is present.
Sinonasal mucosal melanoma. Spindled tumour cells are arranged in intersecting fascicles.
Oral mucosal melanoma. A tumour involving the hard palate, edentulous maxillary alveolar ridge, and buccal mucosa. The pigmented lesion exhibits irregular borders and prominent colour variation.
Oral mucosal melanoma. There is a radial growth phase similar to that in lentiginous melanoma, with atypical pigmented melanocytes in the basal layer spreading laterally and with vertical pagetoid spread, as well as invasive melanocytes in the stroma.
Oral mucosal melanoma. The melanoma cells are highlighted by HMB45 immunohistochemistry.
Sinonasal melanoma. Respiratory epithelium adjacent to tumour shows intraepithelial malignant melanocytes in clusters and as single cells.
Sinonasal mucosal melanoma. Immunohistochemistry for SOX10 highlights single and clustered intraepithelial malignant melanocytes.
Sinonasal mucosal melanoma. Amelanotic melanoma can mimic other sinonasal tumours and requires a panel of immunomarkers, including multiple melanoma markers, which can have variable sensitivity.

Q: In the evaluation of a Metastatic Tumor with neuroendocrine features, strong immunoreactivity for [...] helps confirm a primary pulmonary small cell carcinoma origin rather than a primary Merkel cell carcinoma.
Metastatic small cell carcinoma to the parotid salivary gland. Separating primary neuroendocrine carcinomas (NECs) from metastatic NECs can be challenging, especially when they are of the Merkel cell type. However, this tumour expressed strong immunoreactivity for thyroid transcription factor 1 (TTF1) in a patient with a known pulmonary small cell carcinoma.
A: TTF1
Back Extra: Metastatic Tumor
- Clinical: Metastatic tumours often present as painful or non-painful masses in the head and neck region, with symptoms varying by subsite, such as swelling, pain, bleeding, and cranial nerve deficits.
- Micro: Histopathology of metastatic tumours typically mirrors the primary tumour phenotype, but grade progression may occur. Immunohistochemistry is crucial for confirming the origin of the metastasis.
- Ancillary: Molecular testing, including immunohistochemistry and in situ hybridization, is essential for confirming specific tumour types and identifying genetic alterations associated with the primary tumour.
Reference Gallery:
Metastatic squamous cell carcinoma to the parotid gland. CT shows a large cystic mass within the parotid gland (arrow), which proved to be metastatic cutaneous squamous cell carcinoma.
Metastatic melanoma to the parotid salivary gland. This gross image demonstrates a dark-brown nodular cut surface, representing metastatic melanoma.
Metastatic squamous cell carcinoma to the parotid gland. There is an island of non-keratinizing squamous cell carcinoma with central comedonecrosis within the parotid gland.
Metastatic small cell carcinoma to the parotid salivary gland. Separating primary neuroendocrine carcinomas (NECs) from metastatic NECs can be challenging, especially when they are of the Merkel cell type. However, this tumour expressed strong immunoreactivity for thyroid transcription factor 1 (TTF1) in a patient with a known pulmonary small cell carcinoma.
Metastatic renal cell carcinoma to the gingiva. There is neoplastic replacement of the stroma by a pleomorphic population of epithelial cells with prominent nucleoli. This tumour was identical to a known renal cell carcinoma.
Metastatic renal cell carcinoma to the gingiva. This metastatic renal cell carcinoma was strongly immunoreactive for PAX8 (shown), along with CAIX and RCCm, findings that helped to support a metastatic neoplasm.
Breast carcinoma metastatic to olfactory neuroblastoma. Tumour-to-tumour metastasis often develops as part of a sanctuary site or altered vascularity. Metastatic lobular breast carcinoma is seen here, intermingled with an olfactory neuroblastoma.
Breast carcinoma metastatic to olfactory neuroblastoma. Strong ER immunoreactivity highlights the metastatic breast carcinoma cells in this example of tumour-to-tumour (olfactory neuroblastoma) metastasis.
Metastatic renal cell carcinoma to the sinonasal tract. Sheets of pleomorphic cells with tumour necrosis are noted below an intact respiratory epithelium. Metastatic renal cell carcinoma was confirmed by clinical, imaging, and immunohistochemistry findings.
Metastatic renal cell carcinoma to the sinonasal tract. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CAIX (shown). PAX8 and RCCm were also positive, supporting a diagnosis of metastatic renal cell carcinoma.
Metastatic prostatic adenocarcinoma in the temporal bone. CT of the skull base, showing a lytic deposit of metastatic carcinoma in the right temporal bone (arrows) with polypoid tissue in the external auditory canal.
Metastatic prostatic adenocarcinoma in the temporal bone. Biopsy from the external auditory canal shows cribriform prostatic adenocarcinoma.

Q: When evaluating a Metastatic Tumor in the head and neck (such as the gingiva or sinonasal tract), strong immunohistochemical positivity for [...] and CAIX strongly supports a primary renal cell carcinoma origin.
Metastatic renal cell carcinoma to the gingiva. This metastatic renal cell carcinoma was strongly immunoreactive for PAX8 (shown), along with CAIX and RCCm, findings that helped to support a metastatic neoplasm.
Metastatic renal cell carcinoma to the sinonasal tract. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CAIX (shown). PAX8 and RCCm were also positive, supporting a diagnosis of metastatic renal cell carcinoma.
A: PAX8
Back Extra: Metastatic Tumor
- Clinical: Metastatic tumours often present as painful or non-painful masses in the head and neck region, with symptoms varying by subsite, such as swelling, pain, bleeding, and cranial nerve deficits.
- Micro: Histopathology of metastatic tumours typically mirrors the primary tumour phenotype, but grade progression may occur. Immunohistochemistry is crucial for confirming the origin of the metastasis.
- Ancillary: Molecular testing, including immunohistochemistry and in situ hybridization, is essential for confirming specific tumour types and identifying genetic alterations associated with the primary tumour.
Reference Gallery:
Metastatic squamous cell carcinoma to the parotid gland. CT shows a large cystic mass within the parotid gland (arrow), which proved to be metastatic cutaneous squamous cell carcinoma.
Metastatic melanoma to the parotid salivary gland. This gross image demonstrates a dark-brown nodular cut surface, representing metastatic melanoma.
Metastatic squamous cell carcinoma to the parotid gland. There is an island of non-keratinizing squamous cell carcinoma with central comedonecrosis within the parotid gland.
Metastatic small cell carcinoma to the parotid salivary gland. Separating primary neuroendocrine carcinomas (NECs) from metastatic NECs can be challenging, especially when they are of the Merkel cell type. However, this tumour expressed strong immunoreactivity for thyroid transcription factor 1 (TTF1) in a patient with a known pulmonary small cell carcinoma.
Metastatic renal cell carcinoma to the gingiva. There is neoplastic replacement of the stroma by a pleomorphic population of epithelial cells with prominent nucleoli. This tumour was identical to a known renal cell carcinoma.
Metastatic renal cell carcinoma to the gingiva. This metastatic renal cell carcinoma was strongly immunoreactive for PAX8 (shown), along with CAIX and RCCm, findings that helped to support a metastatic neoplasm.
Breast carcinoma metastatic to olfactory neuroblastoma. Tumour-to-tumour metastasis often develops as part of a sanctuary site or altered vascularity. Metastatic lobular breast carcinoma is seen here, intermingled with an olfactory neuroblastoma.
Breast carcinoma metastatic to olfactory neuroblastoma. Strong ER immunoreactivity highlights the metastatic breast carcinoma cells in this example of tumour-to-tumour (olfactory neuroblastoma) metastasis.
Metastatic renal cell carcinoma to the sinonasal tract. Sheets of pleomorphic cells with tumour necrosis are noted below an intact respiratory epithelium. Metastatic renal cell carcinoma was confirmed by clinical, imaging, and immunohistochemistry findings.
Metastatic renal cell carcinoma to the sinonasal tract. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CAIX (shown). PAX8 and RCCm were also positive, supporting a diagnosis of metastatic renal cell carcinoma.
Metastatic prostatic adenocarcinoma in the temporal bone. CT of the skull base, showing a lytic deposit of metastatic carcinoma in the right temporal bone (arrows) with polypoid tissue in the external auditory canal.
Metastatic prostatic adenocarcinoma in the temporal bone. Biopsy from the external auditory canal shows cribriform prostatic adenocarcinoma.

Q: Gross examination of a Metastatic Tumor in the parotid gland demonstrating a distinctively dark-brown nodular cut surface is highly characteristic of metastatic [...].
Metastatic melanoma to the parotid salivary gland. This gross image demonstrates a dark-brown nodular cut surface, representing metastatic melanoma.
A: melanoma
Back Extra: Metastatic Tumor
- Clinical: Metastatic tumours often present as painful or non-painful masses in the head and neck region, with symptoms varying by subsite, such as swelling, pain, bleeding, and cranial nerve deficits.
- Micro: Histopathology of metastatic tumours typically mirrors the primary tumour phenotype, but grade progression may occur. Immunohistochemistry is crucial for confirming the origin of the metastasis.
- Ancillary: Molecular testing, including immunohistochemistry and in situ hybridization, is essential for confirming specific tumour types and identifying genetic alterations associated with the primary tumour.
Reference Gallery:
Metastatic squamous cell carcinoma to the parotid gland. CT shows a large cystic mass within the parotid gland (arrow), which proved to be metastatic cutaneous squamous cell carcinoma.
Metastatic melanoma to the parotid salivary gland. This gross image demonstrates a dark-brown nodular cut surface, representing metastatic melanoma.
Metastatic squamous cell carcinoma to the parotid gland. There is an island of non-keratinizing squamous cell carcinoma with central comedonecrosis within the parotid gland.
Metastatic small cell carcinoma to the parotid salivary gland. Separating primary neuroendocrine carcinomas (NECs) from metastatic NECs can be challenging, especially when they are of the Merkel cell type. However, this tumour expressed strong immunoreactivity for thyroid transcription factor 1 (TTF1) in a patient with a known pulmonary small cell carcinoma.
Metastatic renal cell carcinoma to the gingiva. There is neoplastic replacement of the stroma by a pleomorphic population of epithelial cells with prominent nucleoli. This tumour was identical to a known renal cell carcinoma.
Metastatic renal cell carcinoma to the gingiva. This metastatic renal cell carcinoma was strongly immunoreactive for PAX8 (shown), along with CAIX and RCCm, findings that helped to support a metastatic neoplasm.
Breast carcinoma metastatic to olfactory neuroblastoma. Tumour-to-tumour metastasis often develops as part of a sanctuary site or altered vascularity. Metastatic lobular breast carcinoma is seen here, intermingled with an olfactory neuroblastoma.
Breast carcinoma metastatic to olfactory neuroblastoma. Strong ER immunoreactivity highlights the metastatic breast carcinoma cells in this example of tumour-to-tumour (olfactory neuroblastoma) metastasis.
Metastatic renal cell carcinoma to the sinonasal tract. Sheets of pleomorphic cells with tumour necrosis are noted below an intact respiratory epithelium. Metastatic renal cell carcinoma was confirmed by clinical, imaging, and immunohistochemistry findings.
Metastatic renal cell carcinoma to the sinonasal tract. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CAIX (shown). PAX8 and RCCm were also positive, supporting a diagnosis of metastatic renal cell carcinoma.
Metastatic prostatic adenocarcinoma in the temporal bone. CT of the skull base, showing a lytic deposit of metastatic carcinoma in the right temporal bone (arrows) with polypoid tissue in the external auditory canal.
Metastatic prostatic adenocarcinoma in the temporal bone. Biopsy from the external auditory canal shows cribriform prostatic adenocarcinoma.

Q: Microscopically, Low-grade nasopharyngeal papillary adenocarcinoma exhibits overlapping, elongated nuclei with fine chromatin and occasional psammoma bodies, closely mimicking the features of [...].
Low-grade nasopharyngeal papillary adenocarcinoma. The nuclei show features similar to those seen in association with papillary thyroid carcinoma, including nuclear enlargement and elongation with dispersed (very fine) nuclear chromatin, and crowding and overlapping.
Low-grade nasopharyngeal papillary adenocarcinoma. Psammomatoid concretions may be identified, which in association with a papillary architecture and nuclear features would suggest a possible diagnosis of papillary thyroid carcinoma.
A: papillary thyroid carcinoma
Back Extra: Low-grade nasopharyngeal papillary adenocarcinoma
- Clinical: Common symptoms include nasal obstruction and blood-stained rhinorrhoea.
- Micro: Characterized by complex papillary and glandular architectures, with mild to moderate nuclear pleomorphism.
- Ancillary: Positively stains for TTF1, but negative for thyroglobulin and PAX8.
Reference Gallery:
Low-grade nasopharyngeal papillary adenocarcinoma. At low magnification, the tumour is diffusely infiltrative with papillary and glandular growth.
Low-grade nasopharyngeal papillary adenocarcinoma. Characteristic papillary architecture with fibrovascular cores.
Low-grade nasopharyngeal papillary adenocarcinoma. The nuclei show features similar to those seen in association with papillary thyroid carcinoma, including nuclear enlargement and elongation with dispersed (very fine) nuclear chromatin, and crowding and overlapping.
Low-grade nasopharyngeal papillary adenocarcinoma. In conjunction with the papillary architecture, the neoplasm may have focal or more widespread areas of complex glandular growth characterized by a microcystic/cribriform pattern and/or back-to-back glands without intervening stroma.
Low-grade nasopharyngeal papillary adenocarcinoma. Psammomatoid concretions may be identified, which in association with a papillary architecture and nuclear features would suggest a possible diagnosis of papillary thyroid carcinoma.
Low-grade nasopharyngeal papillary adenocarcinoma. Transition from normal surface respiratory epithelium to the neoplasm supports a primary origin of this tumour from the nasopharyngeal mucosa and weighs against a possible diagnosis of metastatic papillary thyroid carcinoma.
Low-grade nasopharyngeal papillary adenocarcinoma. The neoplasm is diffusely positive for thyroid transcription factor 1 (TTF1), a characteristic finding, but lacks immunoreactivity for thyroglobulin and PAX8.
Low-grade nasopharyngeal papillary adenocarcinoma. An example showing a prominent component of spindly cells merging with the papillae. The spindly cells exhibit bland-looking nuclei.

Q: Despite its morphologic resemblance to a metastatic thyroid tumor, Low-grade nasopharyngeal papillary adenocarcinoma is characteristically negative for thyroglobulin and PAX8, but exhibits diffuse immunoreactivity for [...].
Low-grade nasopharyngeal papillary adenocarcinoma. The neoplasm is diffusely positive for thyroid transcription factor 1 (TTF1), a characteristic finding, but lacks immunoreactivity for thyroglobulin and PAX8.
A: TTF1
Back Extra: Low-grade nasopharyngeal papillary adenocarcinoma
- Clinical: Common symptoms include nasal obstruction and blood-stained rhinorrhoea.
- Micro: Characterized by complex papillary and glandular architectures, with mild to moderate nuclear pleomorphism.
- Ancillary: Positively stains for TTF1, but negative for thyroglobulin and PAX8.
Reference Gallery:
Low-grade nasopharyngeal papillary adenocarcinoma. At low magnification, the tumour is diffusely infiltrative with papillary and glandular growth.
Low-grade nasopharyngeal papillary adenocarcinoma. Characteristic papillary architecture with fibrovascular cores.
Low-grade nasopharyngeal papillary adenocarcinoma. The nuclei show features similar to those seen in association with papillary thyroid carcinoma, including nuclear enlargement and elongation with dispersed (very fine) nuclear chromatin, and crowding and overlapping.
Low-grade nasopharyngeal papillary adenocarcinoma. In conjunction with the papillary architecture, the neoplasm may have focal or more widespread areas of complex glandular growth characterized by a microcystic/cribriform pattern and/or back-to-back glands without intervening stroma.
Low-grade nasopharyngeal papillary adenocarcinoma. Psammomatoid concretions may be identified, which in association with a papillary architecture and nuclear features would suggest a possible diagnosis of papillary thyroid carcinoma.
Low-grade nasopharyngeal papillary adenocarcinoma. Transition from normal surface respiratory epithelium to the neoplasm supports a primary origin of this tumour from the nasopharyngeal mucosa and weighs against a possible diagnosis of metastatic papillary thyroid carcinoma.
Low-grade nasopharyngeal papillary adenocarcinoma. The neoplasm is diffusely positive for thyroid transcription factor 1 (TTF1), a characteristic finding, but lacks immunoreactivity for thyroglobulin and PAX8.
Low-grade nasopharyngeal papillary adenocarcinoma. An example showing a prominent component of spindly cells merging with the papillae. The spindly cells exhibit bland-looking nuclei.

Q: Histologically, a primary mucosal origin for Low-grade nasopharyngeal papillary adenocarcinoma (as opposed to a metastasis) is supported by observing a morphologic transition from the normal surface [...].
Low-grade nasopharyngeal papillary adenocarcinoma. Transition from normal surface respiratory epithelium to the neoplasm supports a primary origin of this tumour from the nasopharyngeal mucosa and weighs against a possible diagnosis of metastatic papillary thyroid carcinoma.
A: respiratory epithelium
Back Extra: Low-grade nasopharyngeal papillary adenocarcinoma
- Clinical: Common symptoms include nasal obstruction and blood-stained rhinorrhoea.
- Micro: Characterized by complex papillary and glandular architectures, with mild to moderate nuclear pleomorphism.
- Ancillary: Positively stains for TTF1, but negative for thyroglobulin and PAX8.
Reference Gallery:
Low-grade nasopharyngeal papillary adenocarcinoma. At low magnification, the tumour is diffusely infiltrative with papillary and glandular growth.
Low-grade nasopharyngeal papillary adenocarcinoma. Characteristic papillary architecture with fibrovascular cores.
Low-grade nasopharyngeal papillary adenocarcinoma. The nuclei show features similar to those seen in association with papillary thyroid carcinoma, including nuclear enlargement and elongation with dispersed (very fine) nuclear chromatin, and crowding and overlapping.
Low-grade nasopharyngeal papillary adenocarcinoma. In conjunction with the papillary architecture, the neoplasm may have focal or more widespread areas of complex glandular growth characterized by a microcystic/cribriform pattern and/or back-to-back glands without intervening stroma.
Low-grade nasopharyngeal papillary adenocarcinoma. Psammomatoid concretions may be identified, which in association with a papillary architecture and nuclear features would suggest a possible diagnosis of papillary thyroid carcinoma.
Low-grade nasopharyngeal papillary adenocarcinoma. Transition from normal surface respiratory epithelium to the neoplasm supports a primary origin of this tumour from the nasopharyngeal mucosa and weighs against a possible diagnosis of metastatic papillary thyroid carcinoma.
Low-grade nasopharyngeal papillary adenocarcinoma. The neoplasm is diffusely positive for thyroid transcription factor 1 (TTF1), a characteristic finding, but lacks immunoreactivity for thyroglobulin and PAX8.
Low-grade nasopharyngeal papillary adenocarcinoma. An example showing a prominent component of spindly cells merging with the papillae. The spindly cells exhibit bland-looking nuclei.

Q: Microscopically, the undifferentiated subtype of non-keratinizing Nasopharyngeal Carcinoma classically features a [...] growth pattern with indistinct cell borders, large vesicular nuclei, prominent nucleoli, and a dense background of intermingled lymphocytes.
Nasopharyngeal non-keratinizing squamous cell carcinoma, undifferentiated subtype. Example dominated by spindly tumour cells showing indistinct cell borders. The nuclei have fine chromatin and small, distinct nucleoli. There are intermingled small lymphocytes.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, undifferentiated subtype. This example is dominated by spindly tumour cells with indistinct cell borders. The nuclei have fine chromatin and prominent nucleoli.
A: syncytial
Back Extra: Nasopharyngeal Carcinoma
- Clinical: The majority of patients with Nasopharyngeal Carcinoma present with a painless enlarging upper neck mass, often due to involvement of the retropharyngeal and jugulodigastric nodes.
- Micro: Nasopharyngeal Carcinoma commonly shows a syncytial appearance with large vesicular nuclei and prominent nucleoli, intermixed with lymphocytes and plasma cells.
- Ancillary: In situ hybridization for EBV-encoded small RNAs (EBERs) is positive in practically all cases of Nasopharyngeal Carcinoma, particularly in non-keratinizing subtypes.
Reference Gallery:
Nasopharyngeal non-keratinizing squamous cell carcinoma, undifferentiated subtype. Example dominated by spindly tumour cells showing indistinct cell borders. The nuclei have fine chromatin and small, distinct nucleoli. There are intermingled small lymphocytes.
Nasopharyngeal non-keratinizing squamous cell carcinoma. Example dominated by spindly tumour cells. Positive labelling of the tumour cell nuclei for EBV-encoded small RNAs (EBERs) on in situ hybridization supports the diagnosis of nasopharyngeal carcinoma. The tumour cells also show immunoreactivity for cytokeratin and p40 (not shown), supporting their epithelial nature.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, undifferentiated subtype. This example is dominated by spindly tumour cells with indistinct cell borders. The nuclei have fine chromatin and prominent nucleoli.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, undifferentiated subtype. The nasopharyngeal mucosa shows infiltration by sheets and islands of carcinoma beneath an intact surface epithelium, which shows squamous metaplasia.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, undifferentiated subtype. The ulcerated nasopharyngeal mucosa is infiltrated by sheets of carcinoma cells. Necrosis is present.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, undifferentiated subtype. An example with amyloid globules among the carcinoma cells.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma. In situ hybridization for EBV-encoded small RNAs (EBERs) shows positive nuclear labelling of all the tumour cells.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, differentiated subtype. The tumour grows in the form of plexiform sheets, showing some resemblance to urothelial carcinoma.
Nasopharyngeal non-keratinizing squamous cell carcinoma, differentiated subtype. The carcinoma grows in the form of complex anastomosing trabeculae.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, differentiated subtype. The carcinoma cells are polygonal and have a moderate amount of cytoplasm.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, differentiated subtype. Compared with the undifferentiated subtype, the carcinoma cells have more distinct cell borders, a greater amount of cytoplasm, and more chromatin-rich nuclei.
Nasopharyngeal carcinoma. Keratinizing squamous cell carcinoma. This tumour is morphologically similar to keratinizing squamous cell carcinoma commonly seen in other head and neck sites.

Q: In practically all cases of non-keratinizing Nasopharyngeal Carcinoma, tumor cells show strong positive nuclear labeling on in situ hybridization for [...].
Nasopharyngeal non-keratinizing squamous cell carcinoma. Example dominated by spindly tumour cells. Positive labelling of the tumour cell nuclei for EBV-encoded small RNAs (EBERs) on in situ hybridization supports the diagnosis of nasopharyngeal carcinoma. The tumour cells also show immunoreactivity for cytokeratin and p40 (not shown), supporting their epithelial nature.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma. In situ hybridization for EBV-encoded small RNAs (EBERs) shows positive nuclear labelling of all the tumour cells.
A: EBV-encoded small RNAs (EBERs)
Back Extra: Nasopharyngeal Carcinoma
- Clinical: The majority of patients with Nasopharyngeal Carcinoma present with a painless enlarging upper neck mass, often due to involvement of the retropharyngeal and jugulodigastric nodes.
- Micro: Nasopharyngeal Carcinoma commonly shows a syncytial appearance with large vesicular nuclei and prominent nucleoli, intermixed with lymphocytes and plasma cells.
- Ancillary: In situ hybridization for EBV-encoded small RNAs (EBERs) is positive in practically all cases of Nasopharyngeal Carcinoma, particularly in non-keratinizing subtypes.
Reference Gallery:
Nasopharyngeal non-keratinizing squamous cell carcinoma, undifferentiated subtype. Example dominated by spindly tumour cells showing indistinct cell borders. The nuclei have fine chromatin and small, distinct nucleoli. There are intermingled small lymphocytes.
Nasopharyngeal non-keratinizing squamous cell carcinoma. Example dominated by spindly tumour cells. Positive labelling of the tumour cell nuclei for EBV-encoded small RNAs (EBERs) on in situ hybridization supports the diagnosis of nasopharyngeal carcinoma. The tumour cells also show immunoreactivity for cytokeratin and p40 (not shown), supporting their epithelial nature.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, undifferentiated subtype. This example is dominated by spindly tumour cells with indistinct cell borders. The nuclei have fine chromatin and prominent nucleoli.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, undifferentiated subtype. The nasopharyngeal mucosa shows infiltration by sheets and islands of carcinoma beneath an intact surface epithelium, which shows squamous metaplasia.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, undifferentiated subtype. The ulcerated nasopharyngeal mucosa is infiltrated by sheets of carcinoma cells. Necrosis is present.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, undifferentiated subtype. An example with amyloid globules among the carcinoma cells.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma. In situ hybridization for EBV-encoded small RNAs (EBERs) shows positive nuclear labelling of all the tumour cells.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, differentiated subtype. The tumour grows in the form of plexiform sheets, showing some resemblance to urothelial carcinoma.
Nasopharyngeal non-keratinizing squamous cell carcinoma, differentiated subtype. The carcinoma grows in the form of complex anastomosing trabeculae.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, differentiated subtype. The carcinoma cells are polygonal and have a moderate amount of cytoplasm.
Nasopharyngeal carcinoma, non-keratinizing squamous cell carcinoma, differentiated subtype. Compared with the undifferentiated subtype, the carcinoma cells have more distinct cell borders, a greater amount of cytoplasm, and more chromatin-rich nuclei.
Nasopharyngeal carcinoma. Keratinizing squamous cell carcinoma. This tumour is morphologically similar to keratinizing squamous cell carcinoma commonly seen in other head and neck sites.

Q: A Hairy Polyp is classically characterized by squamous epithelium containing [...] overlying mesodermal (fibroadipose) tissue.
Hairy polyp. Squamous epithelium with pilosebaceous units overlying mesodermal (fibroadipose) tissue.
A: pilosebaceous units
Back Extra: Hairy Polyp
- Clinical: Hairy polyps can present with respiratory obstruction, stridor, and feeding difficulties.
- Micro: Hairy polyps are characterized by squamous epithelium with hair follicles and sebaceous units overlying fibroadipose tissue.
- Ancillary: Ancillary studies are not typically required for the diagnosis of hairy polyps.
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Hairy polyp. Squamous epithelium with pilosebaceous units overlying mesodermal (fibroadipose) tissue.
Hairy polyp. Central portion of a hairy polyp containing mesoderm-derived tissue, including fibroadipose tissue and cartilage.

Q: The central core of a Hairy Polyp contains mesoderm-derived tissue, which frequently includes fibroadipose tissue and [...].
Hairy polyp. Central portion of a hairy polyp containing mesoderm-derived tissue, including fibroadipose tissue and cartilage.
A: cartilage
Back Extra: Hairy Polyp
- Clinical: Hairy polyps can present with respiratory obstruction, stridor, and feeding difficulties.
- Micro: Hairy polyps are characterized by squamous epithelium with hair follicles and sebaceous units overlying fibroadipose tissue.
- Ancillary: Ancillary studies are not typically required for the diagnosis of hairy polyps.
Reference Gallery:
Hairy polyp. Squamous epithelium with pilosebaceous units overlying mesodermal (fibroadipose) tissue.
Hairy polyp. Central portion of a hairy polyp containing mesoderm-derived tissue, including fibroadipose tissue and cartilage.

Q: The diagnosis of [...] is classically made in infants presenting with nasal airway obstruction, characterized histologically by a polypoid mass with epithelial tubules, hypocellular myxoid stroma, and squamous eddies continuous with the surface epithelium.
Salivary gland anlage tumour. Polypoid mass with complex squamous proliferation, squamous eddies and myxoid stroma, and ducts connecting to the surface.
Salivary gland anlage tumour. Epithelial tubules and hypocellular myxoid stroma with bland myoepithelial cells.
A: Salivary Gland Anlage Tumor
Back Extra: Salivary Gland Anlage Tumor
- Clinical: Patients present with feeding difficulty and respiratory distress due to nasal airway obstruction, often by 3 months of age.
- Micro: Characterized by a complex network of tubules and ducts, with hypocellular myxoid stroma and squamous nests continuous with the surface epithelium.
- Ancillary: Myoepithelial nature is confirmed by positive immunohistochemistry for cytokeratins and SMA.
Reference Gallery:
Salivary gland anlage tumour. Polypoid mass with complex squamous proliferation, squamous eddies and myxoid stroma, and ducts connecting to the surface.
Salivary gland anlage tumour. Epithelial tubules and hypocellular myxoid stroma with bland myoepithelial cells.
Salivary gland anlage tumour. In the core of the polypoid mass, bland-looking spindle cells merge with tubules and squamous islands.

Q: A highly characteristic microscopic feature of Salivary Gland Anlage Tumor is the presence of a complex network of tubules and ducts intermixed with [...] that uniquely connect to the surface epithelium.
Salivary gland anlage tumour. Polypoid mass with complex squamous proliferation, squamous eddies and myxoid stroma, and ducts connecting to the surface.
Salivary gland anlage tumour. In the core of the polypoid mass, bland-looking spindle cells merge with tubules and squamous islands.
A: squamous nests
Back Extra: Salivary Gland Anlage Tumor
- Clinical: Patients present with feeding difficulty and respiratory distress due to nasal airway obstruction, often by 3 months of age.
- Micro: Characterized by a complex network of tubules and ducts, with hypocellular myxoid stroma and squamous nests continuous with the surface epithelium.
- Ancillary: Myoepithelial nature is confirmed by positive immunohistochemistry for cytokeratins and SMA.
Reference Gallery:
Salivary gland anlage tumour. Polypoid mass with complex squamous proliferation, squamous eddies and myxoid stroma, and ducts connecting to the surface.
Salivary gland anlage tumour. Epithelial tubules and hypocellular myxoid stroma with bland myoepithelial cells.
Salivary gland anlage tumour. In the core of the polypoid mass, bland-looking spindle cells merge with tubules and squamous islands.

Q: Microscopically, a Branchial Cleft Cyst is typically lined by stratified squamous epithelium and characteristically contains abundant [...] within the cyst wall.
Branchial cleft cyst. Lined by stratified squamous epithelium with lymphoid tissue in the cyst wall.
Branchial cleft cyst. Benign stratified squamous epithelium lining a branchial cleft cyst.
A: lymphoid tissue
Back Extra: Branchial Cleft Cyst
- Clinical: Patients present with a painless neck mass that may increase in size after an upper respiratory tract infection.
- Micro: Branchial cleft cysts are usually unilocular and lined with stratified squamous epithelium, often with lymphoid tissue in the cyst wall.
- Ancillary: p16 overexpression is noted in 30-40% of branchial cleft cysts, but high-risk HPV testing should be performed to rule out metastasis from an HPV-associated squamous cell carcinoma.
Reference Gallery:
Branchial cleft cyst. Lined by stratified squamous epithelium with lymphoid tissue in the cyst wall.
Branchial cleft cyst. Benign stratified squamous epithelium lining a branchial cleft cyst.
Branchial cleft cyst. Branchial cleft cyst aspirate (Giemsa) showing inflammatory cells admixed with mature squamous cells and keratinous debris.

Q: On fine needle aspiration, a Branchial Cleft Cyst typically yields an aspirate containing inflammatory cells admixed with mature squamous cells and abundant [...].
Branchial cleft cyst. Branchial cleft cyst aspirate (Giemsa) showing inflammatory cells admixed with mature squamous cells and keratinous debris.
A: keratinous debris
Back Extra: Branchial Cleft Cyst
- Clinical: Patients present with a painless neck mass that may increase in size after an upper respiratory tract infection.
- Micro: Branchial cleft cysts are usually unilocular and lined with stratified squamous epithelium, often with lymphoid tissue in the cyst wall.
- Ancillary: p16 overexpression is noted in 30-40% of branchial cleft cysts, but high-risk HPV testing should be performed to rule out metastasis from an HPV-associated squamous cell carcinoma.
Reference Gallery:
Branchial cleft cyst. Lined by stratified squamous epithelium with lymphoid tissue in the cyst wall.
Branchial cleft cyst. Benign stratified squamous epithelium lining a branchial cleft cyst.
Branchial cleft cyst. Branchial cleft cyst aspirate (Giemsa) showing inflammatory cells admixed with mature squamous cells and keratinous debris.

Q: Grossly and clinically, [...] typically present as firm, palpable cystic masses (often found in areas like the floor of the mouth) that may feature a cutaneous pit secreting sebaceous material and protruding hair follicles.
Dermoid cyst. Excised cystic lesion from the floor of the mouth.
A: Dermoid and Teratoid Cysts
Back Extra: Dermoid and Teratoid Cysts
- Clinical: Patients with Dermoid and Teratoid Cysts often present with a nonspecific, firm, palpable mass, sometimes with a cutaneous pit secreting sebaceous material and protruding hair follicles.
- Micro: The cyst wall of Dermoid and Teratoid Cysts is composed of keratinized, epidermis-like squamous epithelium, with cutaneous adnexal structures including hair follicles or sebaceous, eccrine, or apocrine glandular elements.
- Ancillary: Imaging studies are crucial for Dermoid and Teratoid Cysts to rule out osseous or intracranial extension, with characteristic findings such as hypodense lesions on CT and the 'sack-of-marbles sign' on MRI.
Reference Gallery:
Dermoid cyst. Excised cystic lesion from the floor of the mouth.
Dermoid cyst. Cyst wall composed of epidermis-like squamous epithelium, with associated underlying adnexal structures including sebaceous and focal eccrine glands.

Q: Microscopically, the cyst wall of Dermoid and Teratoid Cysts is lined by an epidermis-like squamous epithelium and distinctively contains underlying cutaneous [...] structures (e.g., sebaceous or eccrine glands).
Dermoid cyst. Cyst wall composed of epidermis-like squamous epithelium, with associated underlying adnexal structures including sebaceous and focal eccrine glands.
A: adnexal
Back Extra: Dermoid and Teratoid Cysts
- Clinical: Patients with Dermoid and Teratoid Cysts often present with a nonspecific, firm, palpable mass, sometimes with a cutaneous pit secreting sebaceous material and protruding hair follicles.
- Micro: The cyst wall of Dermoid and Teratoid Cysts is composed of keratinized, epidermis-like squamous epithelium, with cutaneous adnexal structures including hair follicles or sebaceous, eccrine, or apocrine glandular elements.
- Ancillary: Imaging studies are crucial for Dermoid and Teratoid Cysts to rule out osseous or intracranial extension, with characteristic findings such as hypodense lesions on CT and the 'sack-of-marbles sign' on MRI.
Reference Gallery:
Dermoid cyst. Excised cystic lesion from the floor of the mouth.
Dermoid cyst. Cyst wall composed of epidermis-like squamous epithelium, with associated underlying adnexal structures including sebaceous and focal eccrine glands.

Q: A Lymphoepithelial Cyst typically presents as a unilateral, painless mass in immunocompetent individuals, but bilateral disease is strongly associated with underlying [...] infection.
Lymphoepithelial cyst. A multilocular lymphoepithelial cyst in an immunocompetent patient.
A: HIV
Back Extra: Lymphoepithelial Cyst
- Clinical: Lymphoepithelial cysts present as unilateral, painless masses in immunocompetent individuals; bilateral disease is more common in HIV-positive patients.
- Micro: Lymphoepithelial cysts are dilated cystic structures lined by squamous or columnar epithelium, permeated by mature lymphocytes, and surrounded by a dense lymphoid infiltrate.
- Ancillary: In HIV-positive patients, immunoreactivity for the major HIV-1 core protein p24 can be seen in follicular dendritic cells and interfollicular multinucleated giant cells within the lymphoid stroma.
Reference Gallery:
Lymphoepithelial cyst. A multilocular lymphoepithelial cyst in an immunocompetent patient.
Lymphoepithelial cyst. Benign epithelium of a lymphoepithelial cyst permeated by mature lymphocytes.

Q: Histologically, a Lymphoepithelial Cyst consists of dilated cystic structures lined by squamous or columnar epithelium that is characteristically permeated by [...].
Lymphoepithelial cyst. Benign epithelium of a lymphoepithelial cyst permeated by mature lymphocytes.
A: mature lymphocytes
Back Extra: Lymphoepithelial Cyst
- Clinical: Lymphoepithelial cysts present as unilateral, painless masses in immunocompetent individuals; bilateral disease is more common in HIV-positive patients.
- Micro: Lymphoepithelial cysts are dilated cystic structures lined by squamous or columnar epithelium, permeated by mature lymphocytes, and surrounded by a dense lymphoid infiltrate.
- Ancillary: In HIV-positive patients, immunoreactivity for the major HIV-1 core protein p24 can be seen in follicular dendritic cells and interfollicular multinucleated giant cells within the lymphoid stroma.
Reference Gallery:
Lymphoepithelial cyst. A multilocular lymphoepithelial cyst in an immunocompetent patient.
Lymphoepithelial cyst. Benign epithelium of a lymphoepithelial cyst permeated by mature lymphocytes.

Q: Presenting as a painless, lobulated mass in the floor of the mouth, a [...] is histologically characterized by a cyst-like space filled with extravasated mucin and surrounded by fibroconnective tissue.
Ranula. A cyst-like structure filled with mucin and lined by inflammatory cells and fibrous tissue with adjacent salivary gland and ducts.
Ranula. T2-weighted MRI showing a lobulated T2-hyperintense mass along the floor of the mouth along the lateral left mylohyoid musculature within the sublingual gland.
A: Ranula
Back Extra: Ranula
- Clinical: Ranula typically presents as a painless mass in the floor of the mouth and can extend into the submandibular space (plunging ranula).
- Micro: Histologically, ranula is a cyst-like structure filled with mucin and surrounded by fibroconnective tissue, often containing histiocytes.
- Ancillary: MRI is useful for visualizing the extent of a ranula, particularly in identifying the tail sign in plunging ranula.
Reference Gallery:
Ranula. A cyst-like structure filled with mucin and lined by inflammatory cells and fibrous tissue with adjacent salivary gland and ducts.
Ranula. T2-weighted MRI showing a lobulated T2-hyperintense mass along the floor of the mouth along the lateral left mylohyoid musculature within the sublingual gland.

Q: Histologically, a Ranula appears as a cyst-like structure that typically lacks a true epithelial lining and is primarily filled with extravasated [...] surrounded by fibroconnective tissue and histiocytes.
Ranula. A cyst-like structure filled with mucin and lined by inflammatory cells and fibrous tissue with adjacent salivary gland and ducts.
A: mucin
Back Extra: Ranula
- Clinical: Ranula typically presents as a painless mass in the floor of the mouth and can extend into the submandibular space (plunging ranula).
- Micro: Histologically, ranula is a cyst-like structure filled with mucin and surrounded by fibroconnective tissue, often containing histiocytes.
- Ancillary: MRI is useful for visualizing the extent of a ranula, particularly in identifying the tail sign in plunging ranula.
Reference Gallery:
Ranula. A cyst-like structure filled with mucin and lined by inflammatory cells and fibrous tissue with adjacent salivary gland and ducts.
Ranula. T2-weighted MRI showing a lobulated T2-hyperintense mass along the floor of the mouth along the lateral left mylohyoid musculature within the sublingual gland.

Q: A Thyroglossal Duct Cyst classically presents as a painless, mobile neck mass located in the [...], which characteristically moves upward with swallowing.
Thyroglossal duct cyst. A midline subcutaneous mass is identified at the level of the hyoid bone in this young man.
A: midline
Back Extra: Thyroglossal Duct Cyst
- Clinical: Patients typically present with a mobile, midline, infrahyoid, painless neck mass that moves upward with swallowing. An associated skin fistula is present in about 10% of cases.
- Micro: The cyst is lined by respiratory or squamous epithelium and often contains thyroid follicles. Ruptured cysts may show a metaplastic squamous lining and inflammation.
- Ancillary: Smears from thyroglossal duct cysts are often non-diagnostic, with low cellularity and more inflammatory cells than epithelial cells.
Reference Gallery:
Thyroglossal duct cyst. A midline subcutaneous mass is identified at the level of the hyoid bone in this young man.
Neck thyroglossal duct cyst. A transverse neck ultrasound demonstrates a hypoechoic mass just off the midline in the anterior neck.
Neck thyroglossal duct cyst. T1-weighted axial MRI shows a soft tissue–density mass with low signal intensity, just off the midline at the level of the hyoid bone.
Thyroglossal duct cyst. T2-weighted axial MRI shows a soft tissue–density mass with bright signal intensity, just off the midline at the level of the hyoid bone.
Papillary carcinoma arising in thyroglossal duct cyst. This sagittal CT image shows a cystic lesion immediately adjacent to the hyoid bone. Nodular soft tissue excrescences within the cyst suggested carcinoma, which was confirmed histologically.
Neck thyroglossal duct cyst. Immediately adjacent to the hyoid bone, within the soft tissue, are follicles of thyroid epithelium adjacent to a respiratory epithelium–lined cyst.
Neck thyroglossal duct cyst. The respiratory epithelium–lined cyst is associated with skeletal muscle, minor mucoserous glands, and rare thyroid follicles.
Neck thyroglossal duct cyst. Thyroid follicles are usually identified in the soft tissues immediately adjacent to the cyst. This cyst shows a respiratory epithelium.
Neck thyroglossal duct cyst. Cysts commonly rupture or become inflamed. An example is seen here with a metaplastic squamous lining. Note the thyroid follicles in the cyst wall.
Neck thyroglossal duct cyst. Thyroid gland tissue may be very limited in amount and difficult to identify, although if carefully sought, it can usually be found (arrow).
Papillary carcinoma arising in thyroglossal duct cyst. An ultrasound image of a midline neck cyst with an irregular contour and a nodular soft tissue excrescence projecting into the lumen. This finding is worrisome for carcinoma, which was identified histologically.
Thyroglossal duct cyst. This intraoperative photograph demonstrates a cystic mass on a pedicle towards the base of the tongue.

Q: Histologically, a Thyroglossal Duct Cyst is typically lined by respiratory or squamous epithelium and characteristically contains [...] within the adjacent connective tissue wall.
Neck thyroglossal duct cyst. Immediately adjacent to the hyoid bone, within the soft tissue, are follicles of thyroid epithelium adjacent to a respiratory epithelium–lined cyst.
Neck thyroglossal duct cyst. Thyroid follicles are usually identified in the soft tissues immediately adjacent to the cyst. This cyst shows a respiratory epithelium.
A: thyroid follicles
Back Extra: Thyroglossal Duct Cyst
- Clinical: Patients typically present with a mobile, midline, infrahyoid, painless neck mass that moves upward with swallowing. An associated skin fistula is present in about 10% of cases.
- Micro: The cyst is lined by respiratory or squamous epithelium and often contains thyroid follicles. Ruptured cysts may show a metaplastic squamous lining and inflammation.
- Ancillary: Smears from thyroglossal duct cysts are often non-diagnostic, with low cellularity and more inflammatory cells than epithelial cells.
Reference Gallery:
Thyroglossal duct cyst. A midline subcutaneous mass is identified at the level of the hyoid bone in this young man.
Neck thyroglossal duct cyst. A transverse neck ultrasound demonstrates a hypoechoic mass just off the midline in the anterior neck.
Neck thyroglossal duct cyst. T1-weighted axial MRI shows a soft tissue–density mass with low signal intensity, just off the midline at the level of the hyoid bone.
Thyroglossal duct cyst. T2-weighted axial MRI shows a soft tissue–density mass with bright signal intensity, just off the midline at the level of the hyoid bone.
Papillary carcinoma arising in thyroglossal duct cyst. This sagittal CT image shows a cystic lesion immediately adjacent to the hyoid bone. Nodular soft tissue excrescences within the cyst suggested carcinoma, which was confirmed histologically.
Neck thyroglossal duct cyst. Immediately adjacent to the hyoid bone, within the soft tissue, are follicles of thyroid epithelium adjacent to a respiratory epithelium–lined cyst.
Neck thyroglossal duct cyst. The respiratory epithelium–lined cyst is associated with skeletal muscle, minor mucoserous glands, and rare thyroid follicles.
Neck thyroglossal duct cyst. Thyroid follicles are usually identified in the soft tissues immediately adjacent to the cyst. This cyst shows a respiratory epithelium.
Neck thyroglossal duct cyst. Cysts commonly rupture or become inflamed. An example is seen here with a metaplastic squamous lining. Note the thyroid follicles in the cyst wall.
Neck thyroglossal duct cyst. Thyroid gland tissue may be very limited in amount and difficult to identify, although if carefully sought, it can usually be found (arrow).
Papillary carcinoma arising in thyroglossal duct cyst. An ultrasound image of a midline neck cyst with an irregular contour and a nodular soft tissue excrescence projecting into the lumen. This finding is worrisome for carcinoma, which was identified histologically.
Thyroglossal duct cyst. This intraoperative photograph demonstrates a cystic mass on a pedicle towards the base of the tongue.

Q: Patients with Branchioma most commonly present with a slow-growing subfascial swelling in the [...] region.
Branchioma. A heterogeneous soft tissue mass is noted in the anterior neck above the region of the clavicle.
A: suprasternoclavicular
Back Extra: Branchioma
- Clinical: Patients most commonly present with a slow-growing subfascial suprasternoclavicular swelling, left-sided more often than right-sided.
- Micro: Branchioma is typically well-circumscribed or encapsulated, with a haphazard proliferation of spindled cells, epithelial islands, and adipocytes.
- Ancillary: The plump spindly cells are positive for pancytokeratin, CK5/6, p63, p40, and SMA, indicating myoepithelial differentiation.
Reference Gallery:
Branchioma. A heterogeneous soft tissue mass is noted in the anterior neck above the region of the clavicle.
Branchioma. Low-power view shows a well-circumscribed mass containing numerous cysts and a spindled stroma with adipocytes.
Branchioma. There is a cellular spindled cell population immediately adjacent to and intermingled with an epithelial component with areas of cystic dilatation. Adipocytes are seen throughout.
Branchioma. Various components of branchioma are haphazardly distributed, with squamous-lined cysts adjacent to spindled cells and adipocytes set within fibrous connective tissue.
Branchioma. The features of branchioma may be subtle, with adipocytes and fibrosis partly obscuring the squamous epithelium and associated spindled cells.
Branchioma with carcinoma. In some cases, malignant transformation of the epithelial component may be seen, here showing a complex papillary architecture of cells with moderate pleomorphism and an apocrine morphology.
Branchioma. Fascicles of plump spindly cells with uniform nuclei. The spindle cells in the right field show myoid features, characterized by densely eosinophilic cytoplasm.
Branchioma. An example of monophasic branchioma with an absent to inconspicuous epithelial component. The adipose component is present only very focally.
Branchioma. Immunostaining for pancytokeratin highlights the epithelial and plump spindly cell components. Note the frequent presence of anastomosing narrow strands (upper left).
Branchioma. Immunostaining for SMA highlights the plump spindly cells, while the epithelial component is negative.

Q: The histologic hallmark of Branchioma is a well-circumscribed, haphazard proliferation of epithelial islands, spindled cells, and [...].
Branchioma. Low-power view shows a well-circumscribed mass containing numerous cysts and a spindled stroma with adipocytes.
Branchioma. There is a cellular spindled cell population immediately adjacent to and intermingled with an epithelial component with areas of cystic dilatation. Adipocytes are seen throughout.
Branchioma. Various components of branchioma are haphazardly distributed, with squamous-lined cysts adjacent to spindled cells and adipocytes set within fibrous connective tissue.
A: adipocytes
Back Extra: Branchioma
- Clinical: Patients most commonly present with a slow-growing subfascial suprasternoclavicular swelling, left-sided more often than right-sided.
- Micro: Branchioma is typically well-circumscribed or encapsulated, with a haphazard proliferation of spindled cells, epithelial islands, and adipocytes.
- Ancillary: The plump spindly cells are positive for pancytokeratin, CK5/6, p63, p40, and SMA, indicating myoepithelial differentiation.
Reference Gallery:
Branchioma. A heterogeneous soft tissue mass is noted in the anterior neck above the region of the clavicle.
Branchioma. Low-power view shows a well-circumscribed mass containing numerous cysts and a spindled stroma with adipocytes.
Branchioma. There is a cellular spindled cell population immediately adjacent to and intermingled with an epithelial component with areas of cystic dilatation. Adipocytes are seen throughout.
Branchioma. Various components of branchioma are haphazardly distributed, with squamous-lined cysts adjacent to spindled cells and adipocytes set within fibrous connective tissue.
Branchioma. The features of branchioma may be subtle, with adipocytes and fibrosis partly obscuring the squamous epithelium and associated spindled cells.
Branchioma with carcinoma. In some cases, malignant transformation of the epithelial component may be seen, here showing a complex papillary architecture of cells with moderate pleomorphism and an apocrine morphology.
Branchioma. Fascicles of plump spindly cells with uniform nuclei. The spindle cells in the right field show myoid features, characterized by densely eosinophilic cytoplasm.
Branchioma. An example of monophasic branchioma with an absent to inconspicuous epithelial component. The adipose component is present only very focally.
Branchioma. Immunostaining for pancytokeratin highlights the epithelial and plump spindly cell components. Note the frequent presence of anastomosing narrow strands (upper left).
Branchioma. Immunostaining for SMA highlights the plump spindly cells, while the epithelial component is negative.

Q: In Branchioma, the plump spindly cells exhibit myoepithelial differentiation, characteristically staining positive for pancytokeratin, p63, and [...].
Branchioma. Immunostaining for pancytokeratin highlights the epithelial and plump spindly cell components. Note the frequent presence of anastomosing narrow strands (upper left).
Branchioma. Immunostaining for SMA highlights the plump spindly cells, while the epithelial component is negative.
A: SMA
Back Extra: Branchioma
- Clinical: Patients most commonly present with a slow-growing subfascial suprasternoclavicular swelling, left-sided more often than right-sided.
- Micro: Branchioma is typically well-circumscribed or encapsulated, with a haphazard proliferation of spindled cells, epithelial islands, and adipocytes.
- Ancillary: The plump spindly cells are positive for pancytokeratin, CK5/6, p63, p40, and SMA, indicating myoepithelial differentiation.
Reference Gallery:
Branchioma. A heterogeneous soft tissue mass is noted in the anterior neck above the region of the clavicle.
Branchioma. Low-power view shows a well-circumscribed mass containing numerous cysts and a spindled stroma with adipocytes.
Branchioma. There is a cellular spindled cell population immediately adjacent to and intermingled with an epithelial component with areas of cystic dilatation. Adipocytes are seen throughout.
Branchioma. Various components of branchioma are haphazardly distributed, with squamous-lined cysts adjacent to spindled cells and adipocytes set within fibrous connective tissue.
Branchioma. The features of branchioma may be subtle, with adipocytes and fibrosis partly obscuring the squamous epithelium and associated spindled cells.
Branchioma with carcinoma. In some cases, malignant transformation of the epithelial component may be seen, here showing a complex papillary architecture of cells with moderate pleomorphism and an apocrine morphology.
Branchioma. Fascicles of plump spindly cells with uniform nuclei. The spindle cells in the right field show myoid features, characterized by densely eosinophilic cytoplasm.
Branchioma. An example of monophasic branchioma with an absent to inconspicuous epithelial component. The adipose component is present only very focally.
Branchioma. Immunostaining for pancytokeratin highlights the epithelial and plump spindly cell components. Note the frequent presence of anastomosing narrow strands (upper left).
Branchioma. Immunostaining for SMA highlights the plump spindly cells, while the epithelial component is negative.

Q: The most common histologic subtype of Heterotopia-Associated Carcinoma is [...], which frequently arises within a thyroglossal duct cyst and exhibits characteristic nuclear features alongside benign heterotopic elements.
Heterotopia-associated carcinoma: Papillary thyroid carcinoma arising in a thyroglossal duct cyst. Papillary structures lined by cells with nuclear features of papillary thyroid carcinoma are present within a cyst located in the upper midline neck (left). Skeletal muscle and benign heterotopic glandular structures are also identified (right). This carcinoma arose above the thyroid gland, and no lesions were identified in the thyroid.
Heterotopia-associated carcinoma: Papillary thyroid carcinoma arising in a thyroglossal duct cyst. The complex papillary structures (lower right) are lined by cells with nuclear features of papillary thyroid carcinoma; the heterotopic thyroid tissue (upper left) is composed of simple follicles with bland nuclear features.
A: papillary thyroid carcinoma
Back Extra: Heterotopia-Associated Carcinoma
- Clinical: Most patients present with an asymptomatic neck mass, with rare reports of pain or dysphagia. Heterotopia-associated carcinomas are more common in females and span a wide age range.
- Micro: The most common histology is papillary thyroid carcinoma, with characteristic nuclear features and architecture that may be papillary or follicular, proliferating within a cyst or infiltrating surrounding tissue.
- Ancillary: BRAF p.V600E mutations are common in thyroglossal duct cyst papillary thyroid carcinomas, while heterotopic mucoepidermoid carcinomas often harbor MAML2 rearrangements.
Reference Gallery:
Heterotopia-associated carcinoma: Papillary thyroid carcinoma arising in a thyroglossal duct cyst. Papillary structures lined by cells with nuclear features of papillary thyroid carcinoma are present within a cyst located in the upper midline neck (left). Skeletal muscle and benign heterotopic glandular structures are also identified (right). This carcinoma arose above the thyroid gland, and no lesions were identified in the thyroid.
Heterotopia-associated low-grade mucoepidermoid carcinoma arising in a cervical lymph node. A proliferation of neoplastic glands lined by mucinous and intermediate cells is entirely confined within an encapsulated cervical lymph node. No additional sites of disease were identified in the major or minor salivary glands.
Heterotopia-associated papillary thyroid carcinoma arising in a thyroglossal duct cyst. In addition to proliferating within the lumen of a cyst, this papillary thyroid carcinoma infiltrates surrounding soft tissue. Benign heterotopic thyroid structures are also present.
Heterotopia-associated carcinoma: Papillary thyroid carcinoma arising in a thyroglossal duct cyst. The complex papillary structures (lower right) are lined by cells with nuclear features of papillary thyroid carcinoma; the heterotopic thyroid tissue (upper left) is composed of simple follicles with bland nuclear features.

Q: When a Heterotopia-Associated Carcinoma presents as a mucoepidermoid carcinoma (e.g., arising within an encapsulated cervical lymph node), the tumor often harbors a [...] rearrangement.
Heterotopia-associated low-grade mucoepidermoid carcinoma arising in a cervical lymph node. A proliferation of neoplastic glands lined by mucinous and intermediate cells is entirely confined within an encapsulated cervical lymph node. No additional sites of disease were identified in the major or minor salivary glands.
A: MAML2
Back Extra: Heterotopia-Associated Carcinoma
- Clinical: Most patients present with an asymptomatic neck mass, with rare reports of pain or dysphagia. Heterotopia-associated carcinomas are more common in females and span a wide age range.
- Micro: The most common histology is papillary thyroid carcinoma, with characteristic nuclear features and architecture that may be papillary or follicular, proliferating within a cyst or infiltrating surrounding tissue.
- Ancillary: BRAF p.V600E mutations are common in thyroglossal duct cyst papillary thyroid carcinomas, while heterotopic mucoepidermoid carcinomas often harbor MAML2 rearrangements.
Reference Gallery:
Heterotopia-associated carcinoma: Papillary thyroid carcinoma arising in a thyroglossal duct cyst. Papillary structures lined by cells with nuclear features of papillary thyroid carcinoma are present within a cyst located in the upper midline neck (left). Skeletal muscle and benign heterotopic glandular structures are also identified (right). This carcinoma arose above the thyroid gland, and no lesions were identified in the thyroid.
Heterotopia-associated low-grade mucoepidermoid carcinoma arising in a cervical lymph node. A proliferation of neoplastic glands lined by mucinous and intermediate cells is entirely confined within an encapsulated cervical lymph node. No additional sites of disease were identified in the major or minor salivary glands.
Heterotopia-associated papillary thyroid carcinoma arising in a thyroglossal duct cyst. In addition to proliferating within the lumen of a cyst, this papillary thyroid carcinoma infiltrates surrounding soft tissue. Benign heterotopic thyroid structures are also present.
Heterotopia-associated carcinoma: Papillary thyroid carcinoma arising in a thyroglossal duct cyst. The complex papillary structures (lower right) are lined by cells with nuclear features of papillary thyroid carcinoma; the heterotopic thyroid tissue (upper left) is composed of simple follicles with bland nuclear features.

Q: When Heterotopia-Associated Carcinoma manifests as a papillary thyroid carcinoma within a thyroglossal duct cyst, the neoplastic cells commonly harbor a [...] mutation.
Heterotopia-associated papillary thyroid carcinoma arising in a thyroglossal duct cyst. In addition to proliferating within the lumen of a cyst, this papillary thyroid carcinoma infiltrates surrounding soft tissue. Benign heterotopic thyroid structures are also present.
A: BRAF p.V600E
Back Extra: Heterotopia-Associated Carcinoma
- Clinical: Most patients present with an asymptomatic neck mass, with rare reports of pain or dysphagia. Heterotopia-associated carcinomas are more common in females and span a wide age range.
- Micro: The most common histology is papillary thyroid carcinoma, with characteristic nuclear features and architecture that may be papillary or follicular, proliferating within a cyst or infiltrating surrounding tissue.
- Ancillary: BRAF p.V600E mutations are common in thyroglossal duct cyst papillary thyroid carcinomas, while heterotopic mucoepidermoid carcinomas often harbor MAML2 rearrangements.
Reference Gallery:
Heterotopia-associated carcinoma: Papillary thyroid carcinoma arising in a thyroglossal duct cyst. Papillary structures lined by cells with nuclear features of papillary thyroid carcinoma are present within a cyst located in the upper midline neck (left). Skeletal muscle and benign heterotopic glandular structures are also identified (right). This carcinoma arose above the thyroid gland, and no lesions were identified in the thyroid.
Heterotopia-associated low-grade mucoepidermoid carcinoma arising in a cervical lymph node. A proliferation of neoplastic glands lined by mucinous and intermediate cells is entirely confined within an encapsulated cervical lymph node. No additional sites of disease were identified in the major or minor salivary glands.
Heterotopia-associated papillary thyroid carcinoma arising in a thyroglossal duct cyst. In addition to proliferating within the lumen of a cyst, this papillary thyroid carcinoma infiltrates surrounding soft tissue. Benign heterotopic thyroid structures are also present.
Heterotopia-associated carcinoma: Papillary thyroid carcinoma arising in a thyroglossal duct cyst. The complex papillary structures (lower right) are lined by cells with nuclear features of papillary thyroid carcinoma; the heterotopic thyroid tissue (upper left) is composed of simple follicles with bland nuclear features.

Q: Patients with Squamous Carcinoma of Unknown Primary Site most frequently present clinically with a [...] (often representing a cystic lymph node metastasis from an occult oropharyngeal primary).
Carcinoma of unknown primary. Cystic lymph node metastases of an HPV-associated carcinoma.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. Core biopsy of a neck mass in a patient with an unknown history of cancer.
A: neck mass
Q: Squamous Carcinoma of Unknown Primary Site
- Clinical: The most common presentation of [...] is a neck mass or swelling, and the oropharynx is the most common primary site when identified.
- Micro: [...] often shows non-keratinizing morphology characteristic of HPV-associated SCC.
- Ancillary: High-risk HPV testing and p16 immunohistochemical staining are crucial in diagnosing [...].
Reference Gallery:
Carcinoma of unknown primary. Cystic lymph node metastases of an HPV-associated carcinoma.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. Core biopsy of a neck mass in a patient with an unknown history of cancer.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. Core biopsy of a neck mass in a patient with an unknown history of cancer, showing a non-keratinizing carcinoma.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. p16 immunohistochemical staining highlights HPV-associated carcinoma in a core biopsy of a neck mass in a patient with an unknown history of cancer.
A: Squamous Carcinoma of Unknown Primary Site; Squamous Carcinoma of Unknown Primary Site; Squamous Carcinoma of Unknown Primary Site

Q: Histologically, the metastatic deposits in Squamous Carcinoma of Unknown Primary Site often demonstrate a [...] morphology, which is characteristic of HPV-associated squamous cell carcinoma.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. Core biopsy of a neck mass in a patient with an unknown history of cancer, showing a non-keratinizing carcinoma.
A: non-keratinizing
Q: Squamous Carcinoma of Unknown Primary Site
- Clinical: The most common presentation of [...] is a neck mass or swelling, and the oropharynx is the most common primary site when identified.
- Micro: [...] often shows non-keratinizing morphology characteristic of HPV-associated SCC.
- Ancillary: High-risk HPV testing and p16 immunohistochemical staining are crucial in diagnosing [...].
Reference Gallery:
Carcinoma of unknown primary. Cystic lymph node metastases of an HPV-associated carcinoma.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. Core biopsy of a neck mass in a patient with an unknown history of cancer.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. Core biopsy of a neck mass in a patient with an unknown history of cancer, showing a non-keratinizing carcinoma.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. p16 immunohistochemical staining highlights HPV-associated carcinoma in a core biopsy of a neck mass in a patient with an unknown history of cancer.
A: Squamous Carcinoma of Unknown Primary Site; Squamous Carcinoma of Unknown Primary Site; Squamous Carcinoma of Unknown Primary Site

Q: In the diagnostic evaluation of Squamous Carcinoma of Unknown Primary Site, high-risk HPV testing and [...] immunohistochemical staining are crucial to help identify an occult oropharyngeal primary.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. p16 immunohistochemical staining highlights HPV-associated carcinoma in a core biopsy of a neck mass in a patient with an unknown history of cancer.
A: p16
Q: Squamous Carcinoma of Unknown Primary Site
- Clinical: The most common presentation of [...] is a neck mass or swelling, and the oropharynx is the most common primary site when identified.
- Micro: [...] often shows non-keratinizing morphology characteristic of HPV-associated SCC.
- Ancillary: High-risk HPV testing and p16 immunohistochemical staining are crucial in diagnosing [...].
Reference Gallery:
Carcinoma of unknown primary. Cystic lymph node metastases of an HPV-associated carcinoma.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. Core biopsy of a neck mass in a patient with an unknown history of cancer.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. Core biopsy of a neck mass in a patient with an unknown history of cancer, showing a non-keratinizing carcinoma.
Carcinoma of unknown primary. Metastatic HPV-associated carcinoma. p16 immunohistochemical staining highlights HPV-associated carcinoma in a core biopsy of a neck mass in a patient with an unknown history of cancer.
A: Squamous Carcinoma of Unknown Primary Site; Squamous Carcinoma of Unknown Primary Site; Squamous Carcinoma of Unknown Primary Site

Q: In an Ectopic or Invasive Pituitary Neuroendocrine Tumour (PitNET) / Pituitary Adenoma, tumor cells often infiltrate beneath the sinonasal respiratory mucosa, displaying a monomorphic appearance arranged in nests, alveolar patterns, or [...] with central fibrovascular cores.
Sinonasal pituitary neuroendocrine tumour (PitNET). There is an intact respiratory epithelium overlying a nested to alveolar neuroendocrine tumour.
Sinonasal pituitary neuroendocrine tumour (PitNET). A neoplastic infiltrate is noted between the bone as well as within the bone interstices in this PitNET. Note the pseudorosettes with central fibrovascular cores.
Sinonasal gonadotroph tumour. Tumour cells infiltrate under respiratory mucosa.
A: pseudorosettes
Back Extra: Ectopic or Invasive Pituitary Neuroendocrine Tumour (PitNET) / Pituitary Adenoma
- Clinical: Ectopic or Invasive PitNETs often present with symptoms of endocrinopathies (e.g., Cushing syndrome, acromegaly) or mass effect (e.g., sinusitis, rhinorrhoea).
- Micro: Histologically, PitNETs are characterized by a monomorphic appearance with cells arranged in various patterns such as diffuse, glandular, papillary, and trabecular.
- Ancillary: Immunohistochemistry is essential for confirming adenohypophysial differentiation using pituitary transcription factors and hormones.
Reference Gallery:
Sinonasal pituitary neuroendocrine tumour (PitNET). There is an intact respiratory epithelium overlying a nested to alveolar neuroendocrine tumour.
Sinonasal pituitary neuroendocrine tumour (PitNET). A neoplastic infiltrate is noted between the bone as well as within the bone interstices in this PitNET. Note the pseudorosettes with central fibrovascular cores.
Sinonasal pituitary neuroendocrine tumour (PitNET). A richly vascularized fibrocollagenous background separates the neoplastic cells into islands and nests.
Sinonasal pituitary neuroendocrine tumour (PitNET). In some tumours, there is compression of the neoplastic cells by a heavy collagenized stroma, partly obscuring the neoplastic cells.
Sinonasal pituitary neuroendocrine tumour (PitNET). The neoplastic cells show strong and diffuse nuclear reactivity for PIT1.
Sinonasal pituitary neuroendocrine tumour (PitNET). The neoplastic cells demonstrate a characteristic dot-like paranuclear (Golgi) pancytokeratin immunoreactivity.
Sinonasal pituitary neuroendocrine tumour (PitNET). Many of the tumours within the sinonasal tract will demonstrate hormone immunoreactivity, with prolactin (shown) being one of the most common hormones identified.
Pituitary neuroendocrine tumour (PitNET). Rosettes are seen in some PitNETs, sometimes simulating glandular differentiation.
Sinonasal sparsely granulated lactotroph tumour. Pituitary neuroendocrine tumours (PitNETs) that invade into sinonasal mucosa often show extensive crush artefact on biopsy.
Sinonasal sparsely granulated lactotroph tumour. Despite extensive crush artefact, the tumour cells are recognized to have strong nuclear reactivity for PIT1, confirming adenohypophysial differentiation.
Sinonasal sparsely granulated lactotroph tumour. Despite extensive crush artefact, the tumour cells exhibit cytoplasmic reactivity for prolactin, which has a juxtanuclear dot-like accentuation (inset), confirming differentiation as a sparsely granulated lactotroph tumour.
Sinonasal gonadotroph tumour. Tumour cells infiltrate under respiratory mucosa.

Q: To confirm adenohypophyseal differentiation in an Ectopic or Invasive Pituitary Neuroendocrine Tumour (PitNET) / Pituitary Adenoma (especially when obscured by extensive crush artifact), immunohistochemistry is essential and typically demonstrates strong nuclear reactivity for pituitary transcription factors such as [...].
Sinonasal pituitary neuroendocrine tumour (PitNET). The neoplastic cells show strong and diffuse nuclear reactivity for PIT1.
Sinonasal sparsely granulated lactotroph tumour. Pituitary neuroendocrine tumours (PitNETs) that invade into sinonasal mucosa often show extensive crush artefact on biopsy.
Sinonasal sparsely granulated lactotroph tumour. Despite extensive crush artefact, the tumour cells are recognized to have strong nuclear reactivity for PIT1, confirming adenohypophysial differentiation.
A: PIT1
Back Extra: Ectopic or Invasive Pituitary Neuroendocrine Tumour (PitNET) / Pituitary Adenoma
- Clinical: Ectopic or Invasive PitNETs often present with symptoms of endocrinopathies (e.g., Cushing syndrome, acromegaly) or mass effect (e.g., sinusitis, rhinorrhoea).
- Micro: Histologically, PitNETs are characterized by a monomorphic appearance with cells arranged in various patterns such as diffuse, glandular, papillary, and trabecular.
- Ancillary: Immunohistochemistry is essential for confirming adenohypophysial differentiation using pituitary transcription factors and hormones.
Reference Gallery:
Sinonasal pituitary neuroendocrine tumour (PitNET). There is an intact respiratory epithelium overlying a nested to alveolar neuroendocrine tumour.
Sinonasal pituitary neuroendocrine tumour (PitNET). A neoplastic infiltrate is noted between the bone as well as within the bone interstices in this PitNET. Note the pseudorosettes with central fibrovascular cores.
Sinonasal pituitary neuroendocrine tumour (PitNET). A richly vascularized fibrocollagenous background separates the neoplastic cells into islands and nests.
Sinonasal pituitary neuroendocrine tumour (PitNET). In some tumours, there is compression of the neoplastic cells by a heavy collagenized stroma, partly obscuring the neoplastic cells.
Sinonasal pituitary neuroendocrine tumour (PitNET). The neoplastic cells show strong and diffuse nuclear reactivity for PIT1.
Sinonasal pituitary neuroendocrine tumour (PitNET). The neoplastic cells demonstrate a characteristic dot-like paranuclear (Golgi) pancytokeratin immunoreactivity.
Sinonasal pituitary neuroendocrine tumour (PitNET). Many of the tumours within the sinonasal tract will demonstrate hormone immunoreactivity, with prolactin (shown) being one of the most common hormones identified.
Pituitary neuroendocrine tumour (PitNET). Rosettes are seen in some PitNETs, sometimes simulating glandular differentiation.
Sinonasal sparsely granulated lactotroph tumour. Pituitary neuroendocrine tumours (PitNETs) that invade into sinonasal mucosa often show extensive crush artefact on biopsy.
Sinonasal sparsely granulated lactotroph tumour. Despite extensive crush artefact, the tumour cells are recognized to have strong nuclear reactivity for PIT1, confirming adenohypophysial differentiation.
Sinonasal sparsely granulated lactotroph tumour. Despite extensive crush artefact, the tumour cells exhibit cytoplasmic reactivity for prolactin, which has a juxtanuclear dot-like accentuation (inset), confirming differentiation as a sparsely granulated lactotroph tumour.
Sinonasal gonadotroph tumour. Tumour cells infiltrate under respiratory mucosa.

Q: When an Ectopic or Invasive Pituitary Neuroendocrine Tumour (PitNET) / Pituitary Adenoma differentiates as a sparsely granulated lactotroph tumor, the neoplastic cells characteristically demonstrate a [...] (Golgi) staining pattern for both pancytokeratin and prolactin.
Sinonasal pituitary neuroendocrine tumour (PitNET). The neoplastic cells demonstrate a characteristic dot-like paranuclear (Golgi) pancytokeratin immunoreactivity.
Sinonasal sparsely granulated lactotroph tumour. Despite extensive crush artefact, the tumour cells exhibit cytoplasmic reactivity for prolactin, which has a juxtanuclear dot-like accentuation (inset), confirming differentiation as a sparsely granulated lactotroph tumour.
A: dot-like paranuclear
Back Extra: Ectopic or Invasive Pituitary Neuroendocrine Tumour (PitNET) / Pituitary Adenoma
- Clinical: Ectopic or Invasive PitNETs often present with symptoms of endocrinopathies (e.g., Cushing syndrome, acromegaly) or mass effect (e.g., sinusitis, rhinorrhoea).
- Micro: Histologically, PitNETs are characterized by a monomorphic appearance with cells arranged in various patterns such as diffuse, glandular, papillary, and trabecular.
- Ancillary: Immunohistochemistry is essential for confirming adenohypophysial differentiation using pituitary transcription factors and hormones.
Reference Gallery:
Sinonasal pituitary neuroendocrine tumour (PitNET). There is an intact respiratory epithelium overlying a nested to alveolar neuroendocrine tumour.
Sinonasal pituitary neuroendocrine tumour (PitNET). A neoplastic infiltrate is noted between the bone as well as within the bone interstices in this PitNET. Note the pseudorosettes with central fibrovascular cores.
Sinonasal pituitary neuroendocrine tumour (PitNET). A richly vascularized fibrocollagenous background separates the neoplastic cells into islands and nests.
Sinonasal pituitary neuroendocrine tumour (PitNET). In some tumours, there is compression of the neoplastic cells by a heavy collagenized stroma, partly obscuring the neoplastic cells.
Sinonasal pituitary neuroendocrine tumour (PitNET). The neoplastic cells show strong and diffuse nuclear reactivity for PIT1.
Sinonasal pituitary neuroendocrine tumour (PitNET). The neoplastic cells demonstrate a characteristic dot-like paranuclear (Golgi) pancytokeratin immunoreactivity.
Sinonasal pituitary neuroendocrine tumour (PitNET). Many of the tumours within the sinonasal tract will demonstrate hormone immunoreactivity, with prolactin (shown) being one of the most common hormones identified.
Pituitary neuroendocrine tumour (PitNET). Rosettes are seen in some PitNETs, sometimes simulating glandular differentiation.
Sinonasal sparsely granulated lactotroph tumour. Pituitary neuroendocrine tumours (PitNETs) that invade into sinonasal mucosa often show extensive crush artefact on biopsy.
Sinonasal sparsely granulated lactotroph tumour. Despite extensive crush artefact, the tumour cells are recognized to have strong nuclear reactivity for PIT1, confirming adenohypophysial differentiation.
Sinonasal sparsely granulated lactotroph tumour. Despite extensive crush artefact, the tumour cells exhibit cytoplasmic reactivity for prolactin, which has a juxtanuclear dot-like accentuation (inset), confirming differentiation as a sparsely granulated lactotroph tumour.
Sinonasal gonadotroph tumour. Tumour cells infiltrate under respiratory mucosa.

Q: Microscopically, Large Cell Neuroendocrine Carcinoma (LCNEC) typically forms large organoid nests of tumor cells with peripheral palisading and central [...].
Large cell neuroendocrine carcinoma (LCNEC). Large nests of tumour cells with peripheral palisading and comedonecrosis.
Large cell neuroendocrine carcinoma (LCNEC). Sheets and nests of large cells with abundant cytoplasm, prominent nucleoli, and comedonecrosis.
A: comedonecrosis
Back Extra: Large Cell Neuroendocrine Carcinoma (LCNEC)
- Clinical: Presenting symptoms of Large Cell Neuroendocrine Carcinoma (LCNEC) correspond to anatomical site, with hoarseness or dysphagia in the larynx or oropharynx, and nasal obstruction, epistaxis, or anosmia in the sinonasal tract.
- Micro: LCNEC shows nested, organoid, or trabecular growth patterns with frequent peripheral palisading, rosette formation, and central comedonecrosis. Tumour cells are large with abundant eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli.
- Ancillary: LCNEC should be positive for cytokeratin, particularly CAM5.2, and may show diffuse synaptophysin and INSM1 expression. The Ki-67 index is typically > 20%, and often > 50%.
Reference Gallery:
Large cell neuroendocrine carcinoma (LCNEC). Large nests of tumour cells with peripheral palisading and comedonecrosis.
Large cell neuroendocrine carcinoma (LCNEC). Abundant eosinophilic cytoplasm with prominent nucleoli.
Large cell neuroendocrine carcinoma (LCNEC). Diffuse synaptophysin expression.
Large cell neuroendocrine carcinoma (LCNEC). A subset of oropharyngeal and sinonasal tumours are positive for high-risk HPV by RNA in situ hybridization.
Large cell neuroendocrine carcinoma (LCNEC). Sheets and nests of large cells with abundant cytoplasm, prominent nucleoli, and comedonecrosis.
Large cell neuroendocrine carcinoma (LCNEC). Positivity for a cytokeratin (e.g. CAM5.2) should be seen.
Large cell neuroendocrine carcinoma (LCNEC). INSM1 expression.

Q: Cytologically, the tumor cells of Large Cell Neuroendocrine Carcinoma (LCNEC) are characterized by abundant eosinophilic cytoplasm, vesicular chromatin, and [...].
Large cell neuroendocrine carcinoma (LCNEC). Abundant eosinophilic cytoplasm with prominent nucleoli.
A: prominent nucleoli
Back Extra: Large Cell Neuroendocrine Carcinoma (LCNEC)
- Clinical: Presenting symptoms of Large Cell Neuroendocrine Carcinoma (LCNEC) correspond to anatomical site, with hoarseness or dysphagia in the larynx or oropharynx, and nasal obstruction, epistaxis, or anosmia in the sinonasal tract.
- Micro: LCNEC shows nested, organoid, or trabecular growth patterns with frequent peripheral palisading, rosette formation, and central comedonecrosis. Tumour cells are large with abundant eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli.
- Ancillary: LCNEC should be positive for cytokeratin, particularly CAM5.2, and may show diffuse synaptophysin and INSM1 expression. The Ki-67 index is typically > 20%, and often > 50%.
Reference Gallery:
Large cell neuroendocrine carcinoma (LCNEC). Large nests of tumour cells with peripheral palisading and comedonecrosis.
Large cell neuroendocrine carcinoma (LCNEC). Abundant eosinophilic cytoplasm with prominent nucleoli.
Large cell neuroendocrine carcinoma (LCNEC). Diffuse synaptophysin expression.
Large cell neuroendocrine carcinoma (LCNEC). A subset of oropharyngeal and sinonasal tumours are positive for high-risk HPV by RNA in situ hybridization.
Large cell neuroendocrine carcinoma (LCNEC). Sheets and nests of large cells with abundant cytoplasm, prominent nucleoli, and comedonecrosis.
Large cell neuroendocrine carcinoma (LCNEC). Positivity for a cytokeratin (e.g. CAM5.2) should be seen.
Large cell neuroendocrine carcinoma (LCNEC). INSM1 expression.

Q: Immunohistochemistry for Large Cell Neuroendocrine Carcinoma (LCNEC) typically demonstrates positivity for cytokeratins (e.g., CAM5.2) and neuroendocrine markers like synaptophysin and [...].
Large cell neuroendocrine carcinoma (LCNEC). Diffuse synaptophysin expression.
Large cell neuroendocrine carcinoma (LCNEC). Positivity for a cytokeratin (e.g. CAM5.2) should be seen.
Large cell neuroendocrine carcinoma (LCNEC). INSM1 expression.
A: INSM1
Back Extra: Large Cell Neuroendocrine Carcinoma (LCNEC)
- Clinical: Presenting symptoms of Large Cell Neuroendocrine Carcinoma (LCNEC) correspond to anatomical site, with hoarseness or dysphagia in the larynx or oropharynx, and nasal obstruction, epistaxis, or anosmia in the sinonasal tract.
- Micro: LCNEC shows nested, organoid, or trabecular growth patterns with frequent peripheral palisading, rosette formation, and central comedonecrosis. Tumour cells are large with abundant eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli.
- Ancillary: LCNEC should be positive for cytokeratin, particularly CAM5.2, and may show diffuse synaptophysin and INSM1 expression. The Ki-67 index is typically > 20%, and often > 50%.
Reference Gallery:
Large cell neuroendocrine carcinoma (LCNEC). Large nests of tumour cells with peripheral palisading and comedonecrosis.
Large cell neuroendocrine carcinoma (LCNEC). Abundant eosinophilic cytoplasm with prominent nucleoli.
Large cell neuroendocrine carcinoma (LCNEC). Diffuse synaptophysin expression.
Large cell neuroendocrine carcinoma (LCNEC). A subset of oropharyngeal and sinonasal tumours are positive for high-risk HPV by RNA in situ hybridization.
Large cell neuroendocrine carcinoma (LCNEC). Sheets and nests of large cells with abundant cytoplasm, prominent nucleoli, and comedonecrosis.
Large cell neuroendocrine carcinoma (LCNEC). Positivity for a cytokeratin (e.g. CAM5.2) should be seen.
Large cell neuroendocrine carcinoma (LCNEC). INSM1 expression.

Q: The classic clinical presentation of an asymptomatic, rapidly expanding, violaceous nodule on sun-exposed skin in elderly or immunosuppressed patients (the "AEIOU" mnemonic) is highly characteristic of [...].
Merkel cell carcinoma. A violaceous nodule on the right helix of a 71-year-old man.
Merkel cell carcinoma. Clinical image showing the characteristic AEIOU presentation: a nodule that is asymptomatic, expanding rapidly, often in a patient who is immunosuppressed or older than 50 years, and arising on ultraviolet (UV) radiation–exposed skin.
A: Merkel Cell Carcinoma
Back Extra: Merkel Cell Carcinoma
- Clinical: Merkel cell carcinoma (MCC) typically presents as a rapidly growing, violaceous papule or nodule, often in immunosuppressed or elderly patients.
- Micro: On histology, MCC appears as a densely cellular dermal malignancy with mitotic figures and apoptotic bodies. Tumour cells have scant cytoplasm, round to oval nuclei, and finely granular chromatin.
- Ancillary: Immunohistochemical markers such as CK20 (perinuclear dot-like positivity), synaptophysin, and chromogranin A are crucial for diagnosing MCC. MCPyV LT (CM2B4) positivity is also highly specific.
Reference Gallery:
Merkel cell carcinoma. A violaceous nodule on the right helix of a 71-year-old man.
Merkel cell carcinoma. Clinical image showing the characteristic AEIOU presentation: a nodule that is asymptomatic, expanding rapidly, often in a patient who is immunosuppressed or older than 50 years, and arising on ultraviolet (UV) radiation–exposed skin.
Merkel cell carcinoma. Tumour cells arranged as syncytia and trabeculae with large, irregular nuclei and slight cytoplasm. The nuclei have finely granular chromatin, and mitotic figures are numerous (H&E).
Merkel cell carcinoma. Divergent differentiation may be seen, and squamous cell carcinoma is the most common (H&E).
Merkel cell carcinoma. CK20 immunohistochemistry stains Merkel cell carcinoma with a characteristic perinuclear dot-like positivity.
Merkel cell carcinoma. Merkel cell polyomavirus T-antigen shows nuclear positivity.

Q: On histology, Merkel Cell Carcinoma is a densely cellular dermal malignancy composed of tumor cells with scant cytoplasm, numerous mitotic figures, and nuclei that classically display finely [...] chromatin.
Merkel cell carcinoma. Tumour cells arranged as syncytia and trabeculae with large, irregular nuclei and slight cytoplasm. The nuclei have finely granular chromatin, and mitotic figures are numerous (H&E).
A: granular
Back Extra: Merkel Cell Carcinoma
- Clinical: Merkel cell carcinoma (MCC) typically presents as a rapidly growing, violaceous papule or nodule, often in immunosuppressed or elderly patients.
- Micro: On histology, MCC appears as a densely cellular dermal malignancy with mitotic figures and apoptotic bodies. Tumour cells have scant cytoplasm, round to oval nuclei, and finely granular chromatin.
- Ancillary: Immunohistochemical markers such as CK20 (perinuclear dot-like positivity), synaptophysin, and chromogranin A are crucial for diagnosing MCC. MCPyV LT (CM2B4) positivity is also highly specific.
Reference Gallery:
Merkel cell carcinoma. A violaceous nodule on the right helix of a 71-year-old man.
Merkel cell carcinoma. Clinical image showing the characteristic AEIOU presentation: a nodule that is asymptomatic, expanding rapidly, often in a patient who is immunosuppressed or older than 50 years, and arising on ultraviolet (UV) radiation–exposed skin.
Merkel cell carcinoma. Tumour cells arranged as syncytia and trabeculae with large, irregular nuclei and slight cytoplasm. The nuclei have finely granular chromatin, and mitotic figures are numerous (H&E).
Merkel cell carcinoma. Divergent differentiation may be seen, and squamous cell carcinoma is the most common (H&E).
Merkel cell carcinoma. CK20 immunohistochemistry stains Merkel cell carcinoma with a characteristic perinuclear dot-like positivity.
Merkel cell carcinoma. Merkel cell polyomavirus T-antigen shows nuclear positivity.

Q: In Merkel Cell Carcinoma, the tumor cells frequently demonstrate highly specific nuclear positivity for Merkel cell polyomavirus (MCPyV) and classically show a characteristic [...] positivity pattern with CK20 immunohistochemistry.
Merkel cell carcinoma. CK20 immunohistochemistry stains Merkel cell carcinoma with a characteristic perinuclear dot-like positivity.
Merkel cell carcinoma. Merkel cell polyomavirus T-antigen shows nuclear positivity.
A: perinuclear dot-like
Back Extra: Merkel Cell Carcinoma
- Clinical: Merkel cell carcinoma (MCC) typically presents as a rapidly growing, violaceous papule or nodule, often in immunosuppressed or elderly patients.
- Micro: On histology, MCC appears as a densely cellular dermal malignancy with mitotic figures and apoptotic bodies. Tumour cells have scant cytoplasm, round to oval nuclei, and finely granular chromatin.
- Ancillary: Immunohistochemical markers such as CK20 (perinuclear dot-like positivity), synaptophysin, and chromogranin A are crucial for diagnosing MCC. MCPyV LT (CM2B4) positivity is also highly specific.
Reference Gallery:
Merkel cell carcinoma. A violaceous nodule on the right helix of a 71-year-old man.
Merkel cell carcinoma. Clinical image showing the characteristic AEIOU presentation: a nodule that is asymptomatic, expanding rapidly, often in a patient who is immunosuppressed or older than 50 years, and arising on ultraviolet (UV) radiation–exposed skin.
Merkel cell carcinoma. Tumour cells arranged as syncytia and trabeculae with large, irregular nuclei and slight cytoplasm. The nuclei have finely granular chromatin, and mitotic figures are numerous (H&E).
Merkel cell carcinoma. Divergent differentiation may be seen, and squamous cell carcinoma is the most common (H&E).
Merkel cell carcinoma. CK20 immunohistochemistry stains Merkel cell carcinoma with a characteristic perinuclear dot-like positivity.
Merkel cell carcinoma. Merkel cell polyomavirus T-antigen shows nuclear positivity.

Q: Microscopically, Small Cell Neuroendocrine Carcinoma is characterized by sheets and nests of small hyperchromatic cells with scant cytoplasm, frequent mitoses, abundant apoptotic bodies, and prominent [...].
Small cell neuroendocrine carcinoma (SCNEC). Scant cytoplasm, nuclear moulding, and numerous mitotic figures and apoptotic bodies.
Small cell neuroendocrine carcinoma (SCNEC). Sheets and nests of small hyperchromatic cells with occasional peripheral palisading and rosettes.
A: nuclear molding
Back Extra: Small Cell Neuroendocrine Carcinoma
- Clinical: Symptoms depend on the site of origin: hoarseness or dysphagia in the larynx, nasal obstruction or epistaxis in the sinonasal region.
- Micro: Sheets and nests of small hyperchromatic cells with scant cytoplasm, nuclear moulding, and numerous mitotic figures and apoptotic bodies.
- Ancillary: Positive for cytokeratin (especially CAM5.2), INSM1, and often TTF1; high Ki-67 index (> 20%, often > 70%).
Reference Gallery:
Small cell neuroendocrine carcinoma (SCNEC). Scant cytoplasm, nuclear moulding, and numerous mitotic figures and apoptotic bodies.
Small cell neuroendocrine carcinoma (SCNEC). Sheets and nests of small hyperchromatic cells with occasional peripheral palisading and rosettes.
Small cell neuroendocrine carcinoma (SCNEC). Positivity for high-risk HPV by RNA in situ hybridization is seen in a subset of oropharyngeal and sinonasal cases.
Small cell neuroendocrine carcinoma (SCNEC). Diffuse strong nuclear INSM1 expression.
Small cell neuroendocrine carcinoma (SCNEC). Paranuclear dot-like CAM5.2 expression.

Q: Immunohistochemistry for Small Cell Neuroendocrine Carcinoma often reveals diffuse nuclear positivity for INSM1 and a characteristic [...] staining pattern for low-molecular-weight cytokeratins like CAM5.2.
Small cell neuroendocrine carcinoma (SCNEC). Diffuse strong nuclear INSM1 expression.
Small cell neuroendocrine carcinoma (SCNEC). Paranuclear dot-like CAM5.2 expression.
A: paranuclear dot-like
Back Extra: Small Cell Neuroendocrine Carcinoma
- Clinical: Symptoms depend on the site of origin: hoarseness or dysphagia in the larynx, nasal obstruction or epistaxis in the sinonasal region.
- Micro: Sheets and nests of small hyperchromatic cells with scant cytoplasm, nuclear moulding, and numerous mitotic figures and apoptotic bodies.
- Ancillary: Positive for cytokeratin (especially CAM5.2), INSM1, and often TTF1; high Ki-67 index (> 20%, often > 70%).
Reference Gallery:
Small cell neuroendocrine carcinoma (SCNEC). Scant cytoplasm, nuclear moulding, and numerous mitotic figures and apoptotic bodies.
Small cell neuroendocrine carcinoma (SCNEC). Sheets and nests of small hyperchromatic cells with occasional peripheral palisading and rosettes.
Small cell neuroendocrine carcinoma (SCNEC). Positivity for high-risk HPV by RNA in situ hybridization is seen in a subset of oropharyngeal and sinonasal cases.
Small cell neuroendocrine carcinoma (SCNEC). Diffuse strong nuclear INSM1 expression.
Small cell neuroendocrine carcinoma (SCNEC). Paranuclear dot-like CAM5.2 expression.

Q: Microscopically, a [...] of the larynx typically presents as a mass lesion with a trabecular or organoid architecture underlying the squamous mucosa, consisting of cells with monotonous nuclei and granular, pale, acidophilic cytoplasm.
Neuroendocrine tumour of the larynx. These well-differentiated tumours present as mass lesions and have a trabecular or organoid architecture underlying the squamous mucosa.
A: Neuroendocrine Tumour
Back Extra: Neuroendocrine Tumour
- Clinical: Laryngeal neuroendocrine tumours may cause hoarseness, dysphonia, sore throat, and haemoptysis, and can be asymptomatic and detected incidentally during laryngoscopy.
- Micro: These tumours are composed of cords, trabeculae, or small nests of neuroendocrine cells with granular pale acidophilic cytoplasm and monotonous nuclei.
- Ancillary: Diffuse nuclear INSM1 immunopositivity and cytoplasmic synaptophysin and chromogranin A staining are typical findings.
Reference Gallery:
Neuroendocrine tumour of the larynx. These well-differentiated tumours present as mass lesions and have a trabecular or organoid architecture underlying the squamous mucosa.
Neuroendocrine tumour of the larynx. The tumour cells have intense cytoplasmic positivity for chromogranin A.
Neuroendocrine tumour of the larynx. The proliferative rate of these tumours is generally relatively low, but cut-off levels to define grading are not yet established.

Q: Immunohistochemical evaluation of a Neuroendocrine Tumour typically demonstrates diffuse nuclear INSM1 positivity along with intense cytoplasmic staining for synaptophysin and [...].
Neuroendocrine tumour of the larynx. The tumour cells have intense cytoplasmic positivity for chromogranin A.
A: chromogranin A
Back Extra: Neuroendocrine Tumour
- Clinical: Laryngeal neuroendocrine tumours may cause hoarseness, dysphonia, sore throat, and haemoptysis, and can be asymptomatic and detected incidentally during laryngoscopy.
- Micro: These tumours are composed of cords, trabeculae, or small nests of neuroendocrine cells with granular pale acidophilic cytoplasm and monotonous nuclei.
- Ancillary: Diffuse nuclear INSM1 immunopositivity and cytoplasmic synaptophysin and chromogranin A staining are typical findings.
Reference Gallery:
Neuroendocrine tumour of the larynx. These well-differentiated tumours present as mass lesions and have a trabecular or organoid architecture underlying the squamous mucosa.
Neuroendocrine tumour of the larynx. The tumour cells have intense cytoplasmic positivity for chromogranin A.
Neuroendocrine tumour of the larynx. The proliferative rate of these tumours is generally relatively low, but cut-off levels to define grading are not yet established.

Q: Although specific grading cut-offs are not yet established, the proliferative rate (e.g., Ki-67) of a typical well-differentiated laryngeal [...] is generally relatively low.
Neuroendocrine tumour of the larynx. The proliferative rate of these tumours is generally relatively low, but cut-off levels to define grading are not yet established.
A: Neuroendocrine Tumour
Back Extra: Neuroendocrine Tumour
- Clinical: Laryngeal neuroendocrine tumours may cause hoarseness, dysphonia, sore throat, and haemoptysis, and can be asymptomatic and detected incidentally during laryngoscopy.
- Micro: These tumours are composed of cords, trabeculae, or small nests of neuroendocrine cells with granular pale acidophilic cytoplasm and monotonous nuclei.
- Ancillary: Diffuse nuclear INSM1 immunopositivity and cytoplasmic synaptophysin and chromogranin A staining are typical findings.
Reference Gallery:
Neuroendocrine tumour of the larynx. These well-differentiated tumours present as mass lesions and have a trabecular or organoid architecture underlying the squamous mucosa.
Neuroendocrine tumour of the larynx. The tumour cells have intense cytoplasmic positivity for chromogranin A.
Neuroendocrine tumour of the larynx. The proliferative rate of these tumours is generally relatively low, but cut-off levels to define grading are not yet established.

Q: In Familial Paraganglioma Syndromes, SDH-related tumors characteristically exhibit [...] on H&E and typically express cytoplasmic tyrosine hydroxylase.
SDH-related paraganglioma. These tumours often have abundant granular eosinophilic cytoplasm (shown here). They express cytoplasmic tyrosine hydroxylase. Lack of cytoplasmic SDHB with intact stromal positivity indicates SDH-related disease. Tumours associated with a pseudohypoxia pathway alteration also express inhibin.
SDHB-associated carotid body paraganglioma. The morphological findings of an SDHB-associated carotid body paraganglioma are similar to those of paragangliomas at other sites and of other genetic origins.
A: abundant granular eosinophilic cytoplasm
Q: Familial Paraganglioma Syndromes
- Clinical: Symptoms of [...] include sweating, palpitation, and anxiety; signs include hypertension and tachycardia, often seen in familial paraganglioma syndromes.
- Micro: SDH-related paragangliomas often have [...] and express cytoplasmic tyrosine hydroxylase.
- Ancillary: Loss of [...] immunoreactivity with intact stromal positivity supports the diagnosis of SDH-related disease in familial paraganglioma syndromes.
Reference Gallery:
Familial paraganglioma syndromes. Biochemical and genetic clusters of paragangliomas.
SDH-related paraganglioma. These tumours often have abundant granular eosinophilic cytoplasm (shown here). They express cytoplasmic tyrosine hydroxylase. Lack of cytoplasmic SDHB with intact stromal positivity indicates SDH-related disease. Tumours associated with a pseudohypoxia pathway alteration also express inhibin.
SDH-related paraganglioma. These tumours often have abundant granular eosinophilic cytoplasm. They express cytoplasmic tyrosine hydroxylase. Lack of cytoplasmic SDHB with intact stromal positivity (shown here) indicates SDH-related disease. Tumours associated with a pseudohypoxia pathway alteration also express inhibin.
SDHB-associated carotid body paraganglioma. The morphological findings of an SDHB-associated carotid body paraganglioma are similar to those of paragangliomas at other sites and of other genetic origins.
SDHB-associated carotid body paraganglioma. Immunohistochemistry for SDHB shows loss of the characteristic granular cytoplasmic staining for SDHB in this carotid body paraganglioma.
A: epinephrine/norepinephrine excess; abundant granular eosinophilic cytoplasm; cytoplasmic SDHB

Q: The diagnosis of SDH-related disease in Familial Paraganglioma Syndromes is supported immunohistochemically by the loss of [...] immunoreactivity with intact stromal positivity.
SDH-related paraganglioma. These tumours often have abundant granular eosinophilic cytoplasm. They express cytoplasmic tyrosine hydroxylase. Lack of cytoplasmic SDHB with intact stromal positivity (shown here) indicates SDH-related disease. Tumours associated with a pseudohypoxia pathway alteration also express inhibin.
SDHB-associated carotid body paraganglioma. Immunohistochemistry for SDHB shows loss of the characteristic granular cytoplasmic staining for SDHB in this carotid body paraganglioma.
A: cytoplasmic SDHB
Q: Familial Paraganglioma Syndromes
- Clinical: Symptoms of [...] include sweating, palpitation, and anxiety; signs include hypertension and tachycardia, often seen in familial paraganglioma syndromes.
- Micro: SDH-related paragangliomas often have [...] and express cytoplasmic tyrosine hydroxylase.
- Ancillary: Loss of [...] immunoreactivity with intact stromal positivity supports the diagnosis of SDH-related disease in familial paraganglioma syndromes.
Reference Gallery:
Familial paraganglioma syndromes. Biochemical and genetic clusters of paragangliomas.
SDH-related paraganglioma. These tumours often have abundant granular eosinophilic cytoplasm (shown here). They express cytoplasmic tyrosine hydroxylase. Lack of cytoplasmic SDHB with intact stromal positivity indicates SDH-related disease. Tumours associated with a pseudohypoxia pathway alteration also express inhibin.
SDH-related paraganglioma. These tumours often have abundant granular eosinophilic cytoplasm. They express cytoplasmic tyrosine hydroxylase. Lack of cytoplasmic SDHB with intact stromal positivity (shown here) indicates SDH-related disease. Tumours associated with a pseudohypoxia pathway alteration also express inhibin.
SDHB-associated carotid body paraganglioma. The morphological findings of an SDHB-associated carotid body paraganglioma are similar to those of paragangliomas at other sites and of other genetic origins.
SDHB-associated carotid body paraganglioma. Immunohistochemistry for SDHB shows loss of the characteristic granular cytoplasmic staining for SDHB in this carotid body paraganglioma.
A: epinephrine/norepinephrine excess; abundant granular eosinophilic cytoplasm; cytoplasmic SDHB

Q: Histologically, Head and Neck Paraganglioma classically exhibits tumor cells arranged in a nested, [...] architecture surrounded by a prominent capillary network.
Head and neck paraganglioma. Well-developed cavernous blood vessels are characteristic in head and neck paragangliomas.
Head and neck paraganglioma. Small tumour cell nests composed of chief cells, which have abundant clear cytoplasm and oval-shaped nuclei with fairly low N:C ratios, are surrounded by capillaries. Capillary endothelial cells are evident.
A: zellballen
Back Extra: Head and Neck Paraganglioma
- Clinical: Carotid body paragangliomas often present as asymptomatic mass lesions, while middle ear paragangliomas may present with pulsatile tinnitus or hearing abnormalities.
- Micro: Tumours exhibit a Zellballen architecture with chief cells having abundant pale eosinophilic cytoplasm and well-developed cavernous blood vessels.
- Ancillary: Strong positivity for synaptophysin and GATA3 is characteristic, and SDHB immunohistochemistry or genetic testing can help identify hereditary risk.
Reference Gallery:
Head and neck paraganglioma. Enhanced axial CT. The tumours were located at the right and left carotid bifurcation.
Head and neck paraganglioma. Bilateral carotid tumours and an infra-aortic arch paraganglioma are shown in this coronal FDG PET image.
Head and neck paraganglioma. Anterior coronal view of gadolinium-enhanced T1-weighted MRI of carotid body tumours. These were located at the right and left carotid bifurcations.
Head and neck paraganglioma. Coronal view of a magnetic resonance angiography image of carotid body tumours. The vascular tumours were detected at the carotid bifurcations bilaterally. The patient is a 53-year-old man who has a family history; his elder sister and cousin have middle ear paragangliomas. He was found to have germinal mutations: SDHD c.317G>A (p.G106D).
Head and neck paraganglioma. A carotid body paraganglioma, 37 mm in maximum diameter, sliced to show a cut surface that is tan-coloured, solid, and irregular, with some cystic degeneration.
Head and neck paraganglioma. Carotid body paragangliomas, bilateral. Tumour sizes were 37 × 26 × 14 mm on the left side, and 38 × 34 × 22 mm on the right side. The cut surface of both paragangliomas was tan-coloured, solid, and irregular, with some cystic degeneration. Marked haemorrhagic foci on the right side may have been caused by preoperative embolization.
Head and neck paraganglioma. Well-developed cavernous blood vessels are characteristic in head and neck paragangliomas.
Head and neck paraganglioma. Small tumour cell nests composed of chief cells, which have abundant clear cytoplasm and oval-shaped nuclei with fairly low N:C ratios, are surrounded by capillaries. Capillary endothelial cells are evident.
Head and neck paraganglioma. Synaptophysin immunohistochemistry is strongly positive without exception.
Head and neck paraganglioma. GATA3 is positive in paraganglioma (in those with good tissue preservation).
Head and neck paraganglioma. Vacuolations of variable size are evident in tumour cells in SDH-related paragangliomas, such as this SDHD-deficient example from the carotid body.
Head and neck paraganglioma. SDHD-related carotid body paraganglioma. Emboli in vessels are frequently observed in operated tumour tissue consequent to marked tissue degeneration.

Q: In addition to strong diffuse positivity for neuroendocrine markers such as synaptophysin, Head and Neck Paraganglioma is characteristically positive for the transcription factor [...].
Head and neck paraganglioma. Synaptophysin immunohistochemistry is strongly positive without exception.
Head and neck paraganglioma. GATA3 is positive in paraganglioma (in those with good tissue preservation).
A: GATA3
Back Extra: Head and Neck Paraganglioma
- Clinical: Carotid body paragangliomas often present as asymptomatic mass lesions, while middle ear paragangliomas may present with pulsatile tinnitus or hearing abnormalities.
- Micro: Tumours exhibit a Zellballen architecture with chief cells having abundant pale eosinophilic cytoplasm and well-developed cavernous blood vessels.
- Ancillary: Strong positivity for synaptophysin and GATA3 is characteristic, and SDHB immunohistochemistry or genetic testing can help identify hereditary risk.
Reference Gallery:
Head and neck paraganglioma. Enhanced axial CT. The tumours were located at the right and left carotid bifurcation.
Head and neck paraganglioma. Bilateral carotid tumours and an infra-aortic arch paraganglioma are shown in this coronal FDG PET image.
Head and neck paraganglioma. Anterior coronal view of gadolinium-enhanced T1-weighted MRI of carotid body tumours. These were located at the right and left carotid bifurcations.
Head and neck paraganglioma. Coronal view of a magnetic resonance angiography image of carotid body tumours. The vascular tumours were detected at the carotid bifurcations bilaterally. The patient is a 53-year-old man who has a family history; his elder sister and cousin have middle ear paragangliomas. He was found to have germinal mutations: SDHD c.317G>A (p.G106D).
Head and neck paraganglioma. A carotid body paraganglioma, 37 mm in maximum diameter, sliced to show a cut surface that is tan-coloured, solid, and irregular, with some cystic degeneration.
Head and neck paraganglioma. Carotid body paragangliomas, bilateral. Tumour sizes were 37 × 26 × 14 mm on the left side, and 38 × 34 × 22 mm on the right side. The cut surface of both paragangliomas was tan-coloured, solid, and irregular, with some cystic degeneration. Marked haemorrhagic foci on the right side may have been caused by preoperative embolization.
Head and neck paraganglioma. Well-developed cavernous blood vessels are characteristic in head and neck paragangliomas.
Head and neck paraganglioma. Small tumour cell nests composed of chief cells, which have abundant clear cytoplasm and oval-shaped nuclei with fairly low N:C ratios, are surrounded by capillaries. Capillary endothelial cells are evident.
Head and neck paraganglioma. Synaptophysin immunohistochemistry is strongly positive without exception.
Head and neck paraganglioma. GATA3 is positive in paraganglioma (in those with good tissue preservation).
Head and neck paraganglioma. Vacuolations of variable size are evident in tumour cells in SDH-related paragangliomas, such as this SDHD-deficient example from the carotid body.
Head and neck paraganglioma. SDHD-related carotid body paraganglioma. Emboli in vessels are frequently observed in operated tumour tissue consequent to marked tissue degeneration.

Q: Evaluation of a Head and Neck Paraganglioma should include assessing for hereditary risk, often by testing for mutations or loss of immunohistochemical expression in the [...] complex.
Head and neck paraganglioma. Coronal view of a magnetic resonance angiography image of carotid body tumours. The vascular tumours were detected at the carotid bifurcations bilaterally. The patient is a 53-year-old man who has a family history; his elder sister and cousin have middle ear paragangliomas. He was found to have germinal mutations: SDHD c.317G>A (p.G106D).
Head and neck paraganglioma. Vacuolations of variable size are evident in tumour cells in SDH-related paragangliomas, such as this SDHD-deficient example from the carotid body.
A: succinate dehydrogenase (SDH)
Back Extra: Head and Neck Paraganglioma
- Clinical: Carotid body paragangliomas often present as asymptomatic mass lesions, while middle ear paragangliomas may present with pulsatile tinnitus or hearing abnormalities.
- Micro: Tumours exhibit a Zellballen architecture with chief cells having abundant pale eosinophilic cytoplasm and well-developed cavernous blood vessels.
- Ancillary: Strong positivity for synaptophysin and GATA3 is characteristic, and SDHB immunohistochemistry or genetic testing can help identify hereditary risk.
Reference Gallery:
Head and neck paraganglioma. Enhanced axial CT. The tumours were located at the right and left carotid bifurcation.
Head and neck paraganglioma. Bilateral carotid tumours and an infra-aortic arch paraganglioma are shown in this coronal FDG PET image.
Head and neck paraganglioma. Anterior coronal view of gadolinium-enhanced T1-weighted MRI of carotid body tumours. These were located at the right and left carotid bifurcations.
Head and neck paraganglioma. Coronal view of a magnetic resonance angiography image of carotid body tumours. The vascular tumours were detected at the carotid bifurcations bilaterally. The patient is a 53-year-old man who has a family history; his elder sister and cousin have middle ear paragangliomas. He was found to have germinal mutations: SDHD c.317G>A (p.G106D).
Head and neck paraganglioma. A carotid body paraganglioma, 37 mm in maximum diameter, sliced to show a cut surface that is tan-coloured, solid, and irregular, with some cystic degeneration.
Head and neck paraganglioma. Carotid body paragangliomas, bilateral. Tumour sizes were 37 × 26 × 14 mm on the left side, and 38 × 34 × 22 mm on the right side. The cut surface of both paragangliomas was tan-coloured, solid, and irregular, with some cystic degeneration. Marked haemorrhagic foci on the right side may have been caused by preoperative embolization.
Head and neck paraganglioma. Well-developed cavernous blood vessels are characteristic in head and neck paragangliomas.
Head and neck paraganglioma. Small tumour cell nests composed of chief cells, which have abundant clear cytoplasm and oval-shaped nuclei with fairly low N:C ratios, are surrounded by capillaries. Capillary endothelial cells are evident.
Head and neck paraganglioma. Synaptophysin immunohistochemistry is strongly positive without exception.
Head and neck paraganglioma. GATA3 is positive in paraganglioma (in those with good tissue preservation).
Head and neck paraganglioma. Vacuolations of variable size are evident in tumour cells in SDH-related paragangliomas, such as this SDHD-deficient example from the carotid body.
Head and neck paraganglioma. SDHD-related carotid body paraganglioma. Emboli in vessels are frequently observed in operated tumour tissue consequent to marked tissue degeneration.

Q: Microscopically, Chondroblastoma is characterized by uniform, oval to polygonal cells with nuclear grooves, osteoclast-like giant cells, and a characteristic [...].
Chondroblastoma. Oval to polygonal chondroblasts associated with an eosinophilic cartilaginous matrix.
A: eosinophilic cartilaginous matrix
Back Extra: Chondroblastoma
- Clinical: The most frequent clinical symptom of Chondroblastoma is pain, with additional symptoms like hearing loss, tinnitus, and vertigo when located in the temporal bone.
- Micro: Microscopically, Chondroblastomas are characterized by uniform, eosinophilic, polygonal cells with well-defined borders and nuclear grooves, intermingled with an amorphous eosinophilic matrix containing osteoclast-like giant cells.
- Ancillary: Detection of the H3-3B:c.110A>T p.K37M (K36M) mutation is highly specific for Chondroblastoma and can be useful in confirming the diagnosis.
Reference Gallery:
Chondroblastoma. H3.3B diffuse nuclear expression in the chondroblastic cells (H3.3B immunostain).
Chondroblastoma. Oval to polygonal chondroblasts associated with an eosinophilic cartilaginous matrix.
Chondroblastoma. Expansile and well-delineated tumour in the wall of the right sphenoidal sinus. CT, axial.
Chondroblastoma. Expansile and well-delineated tumour in the wall of the right sphenoidal sinus. CT, lower coronal reconstruction.

Q: The diagnosis of Chondroblastoma can be confirmed by detecting the highly specific [...] mutation, which demonstrates diffuse nuclear expression on immunohistochemistry.
Chondroblastoma. H3.3B diffuse nuclear expression in the chondroblastic cells (H3.3B immunostain).
A: H3.3B K36M
Back Extra: Chondroblastoma
- Clinical: The most frequent clinical symptom of Chondroblastoma is pain, with additional symptoms like hearing loss, tinnitus, and vertigo when located in the temporal bone.
- Micro: Microscopically, Chondroblastomas are characterized by uniform, eosinophilic, polygonal cells with well-defined borders and nuclear grooves, intermingled with an amorphous eosinophilic matrix containing osteoclast-like giant cells.
- Ancillary: Detection of the H3-3B:c.110A>T p.K37M (K36M) mutation is highly specific for Chondroblastoma and can be useful in confirming the diagnosis.
Reference Gallery:
Chondroblastoma. H3.3B diffuse nuclear expression in the chondroblastic cells (H3.3B immunostain).
Chondroblastoma. Oval to polygonal chondroblasts associated with an eosinophilic cartilaginous matrix.
Chondroblastoma. Expansile and well-delineated tumour in the wall of the right sphenoidal sinus. CT, axial.
Chondroblastoma. Expansile and well-delineated tumour in the wall of the right sphenoidal sinus. CT, lower coronal reconstruction.

Q: On computed tomography, an expansile, well-delineated skull base tumor (e.g., in the sphenoidal sinus) presenting with localized pain or hearing loss is characteristic of a [...].
Chondroblastoma. Expansile and well-delineated tumour in the wall of the right sphenoidal sinus. CT, axial.
Chondroblastoma. Expansile and well-delineated tumour in the wall of the right sphenoidal sinus. CT, lower coronal reconstruction.
A: Chondroblastoma
Back Extra: Chondroblastoma
- Clinical: The most frequent clinical symptom of Chondroblastoma is pain, with additional symptoms like hearing loss, tinnitus, and vertigo when located in the temporal bone.
- Micro: Microscopically, Chondroblastomas are characterized by uniform, eosinophilic, polygonal cells with well-defined borders and nuclear grooves, intermingled with an amorphous eosinophilic matrix containing osteoclast-like giant cells.
- Ancillary: Detection of the H3-3B:c.110A>T p.K37M (K36M) mutation is highly specific for Chondroblastoma and can be useful in confirming the diagnosis.
Reference Gallery:
Chondroblastoma. H3.3B diffuse nuclear expression in the chondroblastic cells (H3.3B immunostain).
Chondroblastoma. Oval to polygonal chondroblasts associated with an eosinophilic cartilaginous matrix.
Chondroblastoma. Expansile and well-delineated tumour in the wall of the right sphenoidal sinus. CT, axial.
Chondroblastoma. Expansile and well-delineated tumour in the wall of the right sphenoidal sinus. CT, lower coronal reconstruction.

Q: A characteristic microscopic architectural feature of Chondromyxoid Fibroma is a lobular growth pattern with cellular condensation at the [...] of the lobules.
Chondromyxoid fibroma. Lobular tumour with cellular condensation at the periphery of the lobules.
A: periphery
Back Extra: Chondromyxoid Fibroma
- Clinical: Clinical features of chondromyxoid fibroma (CMF) include tinnitus, visual disturbances, headaches, hearing loss, and sinonasal congestion, depending on the site.
- Micro: CMF consists of a lobular proliferation of spindled and stellate cells with abundant eosinophilic cytoplasm and a chondromyxoid background.
- Ancillary: Immunohistochemistry is typically not required, but CMF shows variable staining for SMA, S100, EMA, and SOX9 and is negative for cytokeratins and GFAP.
Reference Gallery:
Chondromyxoid fibroma. Foci of coarse calcification.
Chondromyxoid fibroma. Head CT, axial view, showing an expansile, osteolytic tumour with matrix mineralization, a sclerotic margin, and cortical thinning, involving the ethmoid bone and left frontal sinus.
Chondromyxoid fibroma. Stellate cells with prominent eosinophilic cytoplasmic processes embedded in a myxoid matrix.
Chondromyxoid fibroma. Lobular tumour with cellular condensation at the periphery of the lobules.

Q: At high magnification, the matrix of a Chondromyxoid Fibroma typically contains spindled and [...] cells with prominent eosinophilic cytoplasmic processes.
Chondromyxoid fibroma. Stellate cells with prominent eosinophilic cytoplasmic processes embedded in a myxoid matrix.
A: stellate
Back Extra: Chondromyxoid Fibroma
- Clinical: Clinical features of chondromyxoid fibroma (CMF) include tinnitus, visual disturbances, headaches, hearing loss, and sinonasal congestion, depending on the site.
- Micro: CMF consists of a lobular proliferation of spindled and stellate cells with abundant eosinophilic cytoplasm and a chondromyxoid background.
- Ancillary: Immunohistochemistry is typically not required, but CMF shows variable staining for SMA, S100, EMA, and SOX9 and is negative for cytokeratins and GFAP.
Reference Gallery:
Chondromyxoid fibroma. Foci of coarse calcification.
Chondromyxoid fibroma. Head CT, axial view, showing an expansile, osteolytic tumour with matrix mineralization, a sclerotic margin, and cortical thinning, involving the ethmoid bone and left frontal sinus.
Chondromyxoid fibroma. Stellate cells with prominent eosinophilic cytoplasmic processes embedded in a myxoid matrix.
Chondromyxoid fibroma. Lobular tumour with cellular condensation at the periphery of the lobules.

Q: Radiographically, craniofacial Chondromyxoid Fibroma often presents as an expansile, [...] tumor with matrix mineralization, cortical thinning, and a sclerotic margin.
Chondromyxoid fibroma. Head CT, axial view, showing an expansile, osteolytic tumour with matrix mineralization, a sclerotic margin, and cortical thinning, involving the ethmoid bone and left frontal sinus.
A: osteolytic
Back Extra: Chondromyxoid Fibroma
- Clinical: Clinical features of chondromyxoid fibroma (CMF) include tinnitus, visual disturbances, headaches, hearing loss, and sinonasal congestion, depending on the site.
- Micro: CMF consists of a lobular proliferation of spindled and stellate cells with abundant eosinophilic cytoplasm and a chondromyxoid background.
- Ancillary: Immunohistochemistry is typically not required, but CMF shows variable staining for SMA, S100, EMA, and SOX9 and is negative for cytokeratins and GFAP.
Reference Gallery:
Chondromyxoid fibroma. Foci of coarse calcification.
Chondromyxoid fibroma. Head CT, axial view, showing an expansile, osteolytic tumour with matrix mineralization, a sclerotic margin, and cortical thinning, involving the ethmoid bone and left frontal sinus.
Chondromyxoid fibroma. Stellate cells with prominent eosinophilic cytoplasmic processes embedded in a myxoid matrix.
Chondromyxoid fibroma. Lobular tumour with cellular condensation at the periphery of the lobules.

Q: Microscopically, [...] features a uniform proliferation of bland spindle cells arranged in intertwining fascicles with abundant interspersed collagen fibers, minimal atypia, and rare mitoses.
Moderately cellular proliferation of bland spindle cells lacking atypia and pleomorphism, with interspersed collagen fibres.
A: Desmoplastic Fibroma of Bone
Back Extra: Desmoplastic Fibroma of Bone
- Clinical: Desmoplastic fibroma of bone typically presents as an asymptomatic swelling or facial asymmetry; other symptoms include pain, trismus, mobile teeth, infection, and bleeding.
- Micro: The tumor is composed of uniform benign spindle cells arranged in intertwining fascicles, with minimal atypia or pleomorphism and rare mitoses.
- Ancillary: DFBs express vimentin, SMA, and MSA, with low Ki-67 expression and lack nuclear β-catenin expression.
Reference Gallery:
Panoramic radiograph shows a desmoplastic fibroma of bone (arrows) with marked bone erosion, extension into the oral cavity, loss of the first permanent molar, resorption of the second primary molar root, and a pushing margin.
Macroscopic appearance of the cut surface, showing the white, whorled banding.
CT shows loss of the lingual cortical bone with soft tissue extension (arrows).
Moderately cellular proliferation of bland spindle cells lacking atypia and pleomorphism, with interspersed collagen fibres.

Q: On macroscopic examination, the cut surface of a Desmoplastic Fibroma of Bone typically exhibits a characteristic [...] banding pattern.
Macroscopic appearance of the cut surface, showing the white, whorled banding.
A: white, whorled
Back Extra: Desmoplastic Fibroma of Bone
- Clinical: Desmoplastic fibroma of bone typically presents as an asymptomatic swelling or facial asymmetry; other symptoms include pain, trismus, mobile teeth, infection, and bleeding.
- Micro: The tumor is composed of uniform benign spindle cells arranged in intertwining fascicles, with minimal atypia or pleomorphism and rare mitoses.
- Ancillary: DFBs express vimentin, SMA, and MSA, with low Ki-67 expression and lack nuclear β-catenin expression.
Reference Gallery:
Panoramic radiograph shows a desmoplastic fibroma of bone (arrows) with marked bone erosion, extension into the oral cavity, loss of the first permanent molar, resorption of the second primary molar root, and a pushing margin.
Macroscopic appearance of the cut surface, showing the white, whorled banding.
CT shows loss of the lingual cortical bone with soft tissue extension (arrows).
Moderately cellular proliferation of bland spindle cells lacking atypia and pleomorphism, with interspersed collagen fibres.

Q: Radiographically, Desmoplastic Fibroma of Bone often presents as a destructive mass with a pushing margin that causes marked [...] and cortical loss, frequently extending into surrounding soft tissue.
Panoramic radiograph shows a desmoplastic fibroma of bone (arrows) with marked bone erosion, extension into the oral cavity, loss of the first permanent molar, resorption of the second primary molar root, and a pushing margin.
CT shows loss of the lingual cortical bone with soft tissue extension (arrows).
A: bone erosion
Back Extra: Desmoplastic Fibroma of Bone
- Clinical: Desmoplastic fibroma of bone typically presents as an asymptomatic swelling or facial asymmetry; other symptoms include pain, trismus, mobile teeth, infection, and bleeding.
- Micro: The tumor is composed of uniform benign spindle cells arranged in intertwining fascicles, with minimal atypia or pleomorphism and rare mitoses.
- Ancillary: DFBs express vimentin, SMA, and MSA, with low Ki-67 expression and lack nuclear β-catenin expression.
Reference Gallery:
Panoramic radiograph shows a desmoplastic fibroma of bone (arrows) with marked bone erosion, extension into the oral cavity, loss of the first permanent molar, resorption of the second primary molar root, and a pushing margin.
Macroscopic appearance of the cut surface, showing the white, whorled banding.
CT shows loss of the lingual cortical bone with soft tissue extension (arrows).
Moderately cellular proliferation of bland spindle cells lacking atypia and pleomorphism, with interspersed collagen fibres.

Q: Histologically, the interconnected trabeculae of bone and osteoid in Osteoblastoma are characteristically rimmed by prominent, often multilayered [...] set in a richly vascular stroma.
Osteoblastoma. Circumscribed edge and characteristic blue-bone appearance. The spaces in osteoid are filled by multilayered large eosinophilic osteoblasts.
Osteoblastoma. Irregular interconnected trabeculae of osteoid, partially mineralized and with resting and reversal lines. There is a prominent, sometimes multilayered osteoblast rim with scattered osteoclasts.
Osteoblastoma. Prominent osteoblastic rimming with a layer of large osteoblasts several cells thick on the bone surface.
A: osteoblasts
Back Extra: Osteoblastoma
- Clinical: Osteoblastoma may be asymptomatic or present with localized swelling and pain. It is a rare tumour that occurs mostly in the second to third decades of life, with a slight female predominance.
- Micro: Osteoblastoma is composed of anastomosing trabeculae of bone and osteoid, rimmed by plump osteoblasts, sometimes with densely mineralized foci, and set in a loose, richly vascular fibrous stroma.
- Ancillary: Recurrent rearrangements of FOS or (less frequently) FOSB define osteoblastoma and osteoid osteoma and are also found in cementoblastoma, suggesting a pathogenetic relationship.
Reference Gallery:
Osteoblastoma. Circumscribed edge and characteristic blue-bone appearance. The spaces in osteoid are filled by multilayered large eosinophilic osteoblasts.
Osteoblastoma. Radiographic appearance of an osteoblastoma in a panoramic radiograph.
Osteoblastoma. CT showing a well-defined but irregular outline and radiolucent rim with dense patchy mineralization centrally.
Osteoblastoma. Immunohistochemistry showing strong nuclear positivity for the transcription factor FOS.
Osteoblastoma. Irregular interconnected trabeculae of osteoid, partially mineralized and with resting and reversal lines. There is a prominent, sometimes multilayered osteoblast rim with scattered osteoclasts.
Osteoblastoma. Prominent osteoblastic rimming with a layer of large osteoblasts several cells thick on the bone surface.

Q: At the molecular level, Osteoblastoma is defined by recurrent rearrangements of the [...] or FOSB genes, which can be demonstrated as strong nuclear positivity on immunohistochemistry.
Osteoblastoma. Immunohistochemistry showing strong nuclear positivity for the transcription factor FOS.
A: FOS
Back Extra: Osteoblastoma
- Clinical: Osteoblastoma may be asymptomatic or present with localized swelling and pain. It is a rare tumour that occurs mostly in the second to third decades of life, with a slight female predominance.
- Micro: Osteoblastoma is composed of anastomosing trabeculae of bone and osteoid, rimmed by plump osteoblasts, sometimes with densely mineralized foci, and set in a loose, richly vascular fibrous stroma.
- Ancillary: Recurrent rearrangements of FOS or (less frequently) FOSB define osteoblastoma and osteoid osteoma and are also found in cementoblastoma, suggesting a pathogenetic relationship.
Reference Gallery:
Osteoblastoma. Circumscribed edge and characteristic blue-bone appearance. The spaces in osteoid are filled by multilayered large eosinophilic osteoblasts.
Osteoblastoma. Radiographic appearance of an osteoblastoma in a panoramic radiograph.
Osteoblastoma. CT showing a well-defined but irregular outline and radiolucent rim with dense patchy mineralization centrally.
Osteoblastoma. Immunohistochemistry showing strong nuclear positivity for the transcription factor FOS.
Osteoblastoma. Irregular interconnected trabeculae of osteoid, partially mineralized and with resting and reversal lines. There is a prominent, sometimes multilayered osteoblast rim with scattered osteoclasts.
Osteoblastoma. Prominent osteoblastic rimming with a layer of large osteoblasts several cells thick on the bone surface.

Q: Radiographically, Osteoblastoma frequently presents on CT imaging as a well-defined lesion with a radiolucent rim and central dense, patchy [...].
Osteoblastoma. CT showing a well-defined but irregular outline and radiolucent rim with dense patchy mineralization centrally.
A: mineralization
Back Extra: Osteoblastoma
- Clinical: Osteoblastoma may be asymptomatic or present with localized swelling and pain. It is a rare tumour that occurs mostly in the second to third decades of life, with a slight female predominance.
- Micro: Osteoblastoma is composed of anastomosing trabeculae of bone and osteoid, rimmed by plump osteoblasts, sometimes with densely mineralized foci, and set in a loose, richly vascular fibrous stroma.
- Ancillary: Recurrent rearrangements of FOS or (less frequently) FOSB define osteoblastoma and osteoid osteoma and are also found in cementoblastoma, suggesting a pathogenetic relationship.
Reference Gallery:
Osteoblastoma. Circumscribed edge and characteristic blue-bone appearance. The spaces in osteoid are filled by multilayered large eosinophilic osteoblasts.
Osteoblastoma. Radiographic appearance of an osteoblastoma in a panoramic radiograph.
Osteoblastoma. CT showing a well-defined but irregular outline and radiolucent rim with dense patchy mineralization centrally.
Osteoblastoma. Immunohistochemistry showing strong nuclear positivity for the transcription factor FOS.
Osteoblastoma. Irregular interconnected trabeculae of osteoid, partially mineralized and with resting and reversal lines. There is a prominent, sometimes multilayered osteoblast rim with scattered osteoclasts.
Osteoblastoma. Prominent osteoblastic rimming with a layer of large osteoblasts several cells thick on the bone surface.

Q: In Osteochondroma, the characteristic exophytic bony projection merges with the underlying trabecular bone and is covered by a distinct [...].
Osteochondroma. Cartilaginous cap covered by periosteum at the surface, merging with underlying trabecular bone.
A: cartilaginous cap
Back Extra: Osteochondroma
- Clinical: Osteochondromas in the maxillofacial region often cause swelling, asymmetry, trismus, and temporomandibular joint dysfunction.
- Micro: Osteochondroma is characterized by a cartilage-capped bony projection with cortical and medullary continuity with the parent bone.
- Ancillary: Homozygous deletions of EXT1 are associated with sporadic osteochondromas, suggesting a neoplastic rather than developmental condition.
Reference Gallery:
Osteochondroma. Cartilaginous cap covered by periosteum at the surface, merging with underlying trabecular bone.

Q: On radiographic imaging, an osteoma classically presents as a well-defined, heavily ossified mass or dense [...] arising from the bone surface, frequently involving the paranasal sinuses.
Osteoma of the right frontal sinus. Frontal radiograph demonstrating a heavily ossified mass in the sinus, arising from the bone surface.
Osteoma of the right frontal sinus. Sagittal reformatted CT demonstrating a heavily ossified mass in the sinus, arising from the bone surface.
A: radiopacity
Back Extra: Osteoma
- Clinical: Central osteomas are often asymptomatic, while surface osteomas may present with a slow-growing swelling, facial distortion, or altered dental occlusion.
- Micro: Osteomas are composed mostly of lamellar bone, compact or trabecular, with osteoblasts and osteoclasts usually inconspicuous.
- Ancillary: Imaging shows dense radiopacities with well-defined margins.
Reference Gallery:
Osteoma, surface type. Osteoma of the maxillary sinus, with a dense, smooth swelling of compact mature bone with focal more cellular osteoblast-like areas centrally.
Osteoma of the right frontal sinus. Frontal radiograph demonstrating a heavily ossified mass in the sinus, arising from the bone surface.
Osteoma of the right frontal sinus. Sagittal reformatted CT demonstrating a heavily ossified mass in the sinus, arising from the bone surface.

Q: Histologically, an osteoma is characteristically composed of dense, mature [...] (either compact or trabecular) with relatively inconspicuous osteoblasts and osteoclasts.
Osteoma, surface type. Osteoma of the maxillary sinus, with a dense, smooth swelling of compact mature bone with focal more cellular osteoblast-like areas centrally.
A: lamellar bone
Back Extra: Osteoma
- Clinical: Central osteomas are often asymptomatic, while surface osteomas may present with a slow-growing swelling, facial distortion, or altered dental occlusion.
- Micro: Osteomas are composed mostly of lamellar bone, compact or trabecular, with osteoblasts and osteoclasts usually inconspicuous.
- Ancillary: Imaging shows dense radiopacities with well-defined margins.
Reference Gallery:
Osteoma, surface type. Osteoma of the maxillary sinus, with a dense, smooth swelling of compact mature bone with focal more cellular osteoblast-like areas centrally.
Osteoma of the right frontal sinus. Frontal radiograph demonstrating a heavily ossified mass in the sinus, arising from the bone surface.
Osteoma of the right frontal sinus. Sagittal reformatted CT demonstrating a heavily ossified mass in the sinus, arising from the bone surface.

Q: Adenoid Ameloblastoma is a jaw tumor histologically characterized by a cribriform architecture, duct-like structures, epithelial whorls (morules), and the deposition of [...].
Adenoid ameloblastoma. Duct-like structures, epithelial whorls, and clear cells in close approximation to dentinoid.
Adenoid ameloblastoma. A partly cystic tumour demonstrating a cribriform architecture towards the top of the section. Ameloblastoma-like configuration, duct-like structures, epithelial whorls or morules, and dentinoid are present.
A: dentinoid
Back Extra: Adenoid Ameloblastoma
- Clinical: Adenoid ameloblastoma typically presents as a painless swelling, with a mean diameter of 40 mm, and may show radiolucent unilocular lesions with well-defined boundaries.
- Micro: The tumor is characterized by a cribriform arrangement of basal ameloblast-like cells, with duct-like structures, whorled cellular condensations (morules), and dentinoid.
- Ancillary: CTNNB1 mutations are common in adenoid ameloblastoma, while BRAF p.V600E mutations, typical of other ameloblastomas, are absent.
Reference Gallery:
Adenoid ameloblastoma. Characteristic cribriform architecture with pseudocysts, duct-like structures, and whorls or morules.
Adenoid ameloblastoma. Focal ghost cell keratinization.
Adenoid ameloblastoma. Duct-like structures, epithelial whorls, and clear cells in close approximation to dentinoid.
Adenoid ameloblastoma. A partly cystic tumour demonstrating a cribriform architecture towards the top of the section. Ameloblastoma-like configuration, duct-like structures, epithelial whorls or morules, and dentinoid are present.

Q: Adenoid Ameloblastoma characteristically demonstrates a [...] arrangement of basal ameloblast-like cells with pseudocysts and whorled cellular condensations.
Adenoid ameloblastoma. Characteristic cribriform architecture with pseudocysts, duct-like structures, and whorls or morules.
A: cribriform
Back Extra: Adenoid Ameloblastoma
- Clinical: Adenoid ameloblastoma typically presents as a painless swelling, with a mean diameter of 40 mm, and may show radiolucent unilocular lesions with well-defined boundaries.
- Micro: The tumor is characterized by a cribriform arrangement of basal ameloblast-like cells, with duct-like structures, whorled cellular condensations (morules), and dentinoid.
- Ancillary: CTNNB1 mutations are common in adenoid ameloblastoma, while BRAF p.V600E mutations, typical of other ameloblastomas, are absent.
Reference Gallery:
Adenoid ameloblastoma. Characteristic cribriform architecture with pseudocysts, duct-like structures, and whorls or morules.
Adenoid ameloblastoma. Focal ghost cell keratinization.
Adenoid ameloblastoma. Duct-like structures, epithelial whorls, and clear cells in close approximation to dentinoid.
Adenoid ameloblastoma. A partly cystic tumour demonstrating a cribriform architecture towards the top of the section. Ameloblastoma-like configuration, duct-like structures, epithelial whorls or morules, and dentinoid are present.

Q: Adenoid Ameloblastoma may occasionally exhibit focal areas of [...] keratinization in addition to its classic structural findings.
Adenoid ameloblastoma. Focal ghost cell keratinization.
A: ghost cell
Back Extra: Adenoid Ameloblastoma
- Clinical: Adenoid ameloblastoma typically presents as a painless swelling, with a mean diameter of 40 mm, and may show radiolucent unilocular lesions with well-defined boundaries.
- Micro: The tumor is characterized by a cribriform arrangement of basal ameloblast-like cells, with duct-like structures, whorled cellular condensations (morules), and dentinoid.
- Ancillary: CTNNB1 mutations are common in adenoid ameloblastoma, while BRAF p.V600E mutations, typical of other ameloblastomas, are absent.
Reference Gallery:
Adenoid ameloblastoma. Characteristic cribriform architecture with pseudocysts, duct-like structures, and whorls or morules.
Adenoid ameloblastoma. Focal ghost cell keratinization.
Adenoid ameloblastoma. Duct-like structures, epithelial whorls, and clear cells in close approximation to dentinoid.
Adenoid ameloblastoma. A partly cystic tumour demonstrating a cribriform architecture towards the top of the section. Ameloblastoma-like configuration, duct-like structures, epithelial whorls or morules, and dentinoid are present.

Q: Histologically, Adenomatoid Odontogenic Tumor is characterized by nodules of epithelial cells forming distinctive [...], often associated with eosinophilic amorphous material.
Adenomatoid odontogenic tumour. Tumour showing prominent epithelial proliferation organized in solid nodules and strands formed by cuboidal odontogenic epithelial cells, with round arrays of back-to-back columnar cells.
Adenomatoid odontogenic tumour. Extrafollicular example. A fibrous capsule encloses odontogenic epithelium organized in solid nodules and strands of varying size containing duct-like structures and focal calcification in a haemorrhagic stroma.
A: rosette- or duct-like structures
Back Extra: Adenomatoid Odontogenic Tumor
- Clinical: Adenomatoid Odontogenic Tumor (AOT) typically presents as a well-defined, unilocular radiolucency around an unerupted tooth, often causing tooth displacement and root resorption.
- Micro: AOT is characterized by variably sized nodules of spindle, cuboidal, and columnar epithelial cells forming rosette- or duct-like structures, with eosinophilic amorphous secretory material similar to enamel matrix.
- Ancillary: KRAS p.G12V and p.G12R mutations are commonly detected in AOTs, independent of clinicopathological features.
Reference Gallery:
Adenomatoid odontogenic tumour. Gross features of a follicular adenomatoid odontogenic tumour showing a thick fibrous capsule around the crown of a permanent premolar, with intraluminal proliferation.
Adenomatoid odontogenic tumour. Tumour showing prominent epithelial proliferation organized in solid nodules and strands formed by cuboidal odontogenic epithelial cells, with round arrays of back-to-back columnar cells.
Adenomatoid odontogenic tumour. Extrafollicular example. A fibrous capsule encloses odontogenic epithelium organized in solid nodules and strands of varying size containing duct-like structures and focal calcification in a haemorrhagic stroma.
Adenomatoid odontogenic tumour. Cropped panoramic radiograph showing an adenomatoid odontogenic tumour with cyst formation on the upper first premolar. The corticated radiolucency is associated with tooth root displacement. There is no visible internal mineralization.
Adenomatoid odontogenic tumour. Cone-beam imaging of an adenomatoid odontogenic tumour showing a relatively well-defined radiolucency containing small speckles of mineralization (axial).
Adenomatoid odontogenic tumour. Cone-beam imaging of an adenomatoid odontogenic tumour showing a relatively well-defined radiolucency containing small speckles of mineralization (3D reconstruction).
Adenomatoid odontogenic tumour. Cone-beam imaging of an adenomatoid odontogenic tumour showing a relatively well-defined radiolucency containing small speckles of mineralization (panoramic reconstruction).

Q: Clinically and radiographically, a follicular Adenomatoid Odontogenic Tumor typically presents as a well-defined radiolucency surrounding the crown of an [...], sometimes containing small speckles of mineralization.
Adenomatoid odontogenic tumour. Gross features of a follicular adenomatoid odontogenic tumour showing a thick fibrous capsule around the crown of a permanent premolar, with intraluminal proliferation.
Adenomatoid odontogenic tumour. Cropped panoramic radiograph showing an adenomatoid odontogenic tumour with cyst formation on the upper first premolar. The corticated radiolucency is associated with tooth root displacement. There is no visible internal mineralization.
Adenomatoid odontogenic tumour. Cone-beam imaging of an adenomatoid odontogenic tumour showing a relatively well-defined radiolucency containing small speckles of mineralization (axial).
A: unerupted tooth
Back Extra: Adenomatoid Odontogenic Tumor
- Clinical: Adenomatoid Odontogenic Tumor (AOT) typically presents as a well-defined, unilocular radiolucency around an unerupted tooth, often causing tooth displacement and root resorption.
- Micro: AOT is characterized by variably sized nodules of spindle, cuboidal, and columnar epithelial cells forming rosette- or duct-like structures, with eosinophilic amorphous secretory material similar to enamel matrix.
- Ancillary: KRAS p.G12V and p.G12R mutations are commonly detected in AOTs, independent of clinicopathological features.
Reference Gallery:
Adenomatoid odontogenic tumour. Gross features of a follicular adenomatoid odontogenic tumour showing a thick fibrous capsule around the crown of a permanent premolar, with intraluminal proliferation.
Adenomatoid odontogenic tumour. Tumour showing prominent epithelial proliferation organized in solid nodules and strands formed by cuboidal odontogenic epithelial cells, with round arrays of back-to-back columnar cells.
Adenomatoid odontogenic tumour. Extrafollicular example. A fibrous capsule encloses odontogenic epithelium organized in solid nodules and strands of varying size containing duct-like structures and focal calcification in a haemorrhagic stroma.
Adenomatoid odontogenic tumour. Cropped panoramic radiograph showing an adenomatoid odontogenic tumour with cyst formation on the upper first premolar. The corticated radiolucency is associated with tooth root displacement. There is no visible internal mineralization.
Adenomatoid odontogenic tumour. Cone-beam imaging of an adenomatoid odontogenic tumour showing a relatively well-defined radiolucency containing small speckles of mineralization (axial).
Adenomatoid odontogenic tumour. Cone-beam imaging of an adenomatoid odontogenic tumour showing a relatively well-defined radiolucency containing small speckles of mineralization (3D reconstruction).
Adenomatoid odontogenic tumour. Cone-beam imaging of an adenomatoid odontogenic tumour showing a relatively well-defined radiolucency containing small speckles of mineralization (panoramic reconstruction).

Q: The classic follicular histologic pattern of Conventional Ameloblastoma features peripheral palisaded ameloblast-like cells with reverse polarity and central loose cells resembling the [...].
Ameloblastoma, conventional. Follicular pattern, with acanthomatous change in the large cyst. Peripheral epithelial cells in the islands have hyperchromatic nuclei in a palisading pattern, reverse polarity, and often cytoplasmic vacuolation.
Ameloblastoma, conventional. High-power view of the follicular pattern showing peripheral ameloblast-like cells with palisaded nuclei, reverse polarity, and cytoplasmic vacuolation; and looser, stellate reticulum–like cells in the centre of the follicles.
A: stellate reticulum
Back Extra: Conventional Ameloblastoma
- Clinical: Conventional ameloblastomas present as a painless, slow-growing mass that can displace and loosen teeth, expand and perforate the cortices, and cause facial disfigurement.
- Micro: The most common histological subtype of conventional ameloblastoma is the follicular pattern, characterized by islands of epithelium with peripheral ameloblast-like cells and central stellate reticulum-like cells.
- Ancillary: BRAF p.V600E mutations are the most common activating mutations in conventional ameloblastomas, and immunohistochemical staining can be used to detect these mutations.
Reference Gallery:
Ameloblastoma, conventional. Plexiform histological pattern with anastomosing cords and strands of tumour.
Ameloblastoma, conventional. The most commonly identified oncogenic mutations and their relative frequencies in ameloblastoma (AM) and unicystic ameloblastoma (UAM) located in the mandible or maxilla {24374844; 24993163; 24859340; 30216733}.
Ameloblastoma, conventional. Mixed pattern, with larger, rounded, pale-staining areas characteristic of the follicular histological pattern and focally acanthomatous, spiky, darker-staining islands with more cellular central areas, characteristic of the desmoplastic pattern.
Ameloblastoma, conventional. Large ameloblastoma of the mandible, causing facial deformity.
Ameloblastoma, conventional. Panoramic radiograph of an ameloblastoma forming a typical radiolucent, multilocular, soap bubble–pattern lesion with cortical expansion, tooth displacement, and root resorption.
Ameloblastoma, conventional. 3D CT reconstruction highlights expansion and the multilocularity of the tumour.
Ameloblastoma, conventional. Positive immunohistochemical staining for p.V600E-mutant BRAF in ameloblastoma epithelium. The staining is cytoplasmic.
Ameloblastoma, conventional. Follicular pattern, with acanthomatous change in the large cyst. Peripheral epithelial cells in the islands have hyperchromatic nuclei in a palisading pattern, reverse polarity, and often cytoplasmic vacuolation.
Ameloblastoma, conventional. High-power view of the follicular pattern showing peripheral ameloblast-like cells with palisaded nuclei, reverse polarity, and cytoplasmic vacuolation; and looser, stellate reticulum–like cells in the centre of the follicles.

Q: On panoramic radiographs, Conventional Ameloblastoma frequently presents as an expansile, multilocular radiolucency with a characteristic [...] appearance that can cause root resorption and tooth displacement.
Ameloblastoma, conventional. Panoramic radiograph of an ameloblastoma forming a typical radiolucent, multilocular, soap bubble–pattern lesion with cortical expansion, tooth displacement, and root resorption.
Ameloblastoma, conventional. 3D CT reconstruction highlights expansion and the multilocularity of the tumour.
A: "soap bubble"
Back Extra: Conventional Ameloblastoma
- Clinical: Conventional ameloblastomas present as a painless, slow-growing mass that can displace and loosen teeth, expand and perforate the cortices, and cause facial disfigurement.
- Micro: The most common histological subtype of conventional ameloblastoma is the follicular pattern, characterized by islands of epithelium with peripheral ameloblast-like cells and central stellate reticulum-like cells.
- Ancillary: BRAF p.V600E mutations are the most common activating mutations in conventional ameloblastomas, and immunohistochemical staining can be used to detect these mutations.
Reference Gallery:
Ameloblastoma, conventional. Plexiform histological pattern with anastomosing cords and strands of tumour.
Ameloblastoma, conventional. The most commonly identified oncogenic mutations and their relative frequencies in ameloblastoma (AM) and unicystic ameloblastoma (UAM) located in the mandible or maxilla {24374844; 24993163; 24859340; 30216733}.
Ameloblastoma, conventional. Mixed pattern, with larger, rounded, pale-staining areas characteristic of the follicular histological pattern and focally acanthomatous, spiky, darker-staining islands with more cellular central areas, characteristic of the desmoplastic pattern.
Ameloblastoma, conventional. Large ameloblastoma of the mandible, causing facial deformity.
Ameloblastoma, conventional. Panoramic radiograph of an ameloblastoma forming a typical radiolucent, multilocular, soap bubble–pattern lesion with cortical expansion, tooth displacement, and root resorption.
Ameloblastoma, conventional. 3D CT reconstruction highlights expansion and the multilocularity of the tumour.
Ameloblastoma, conventional. Positive immunohistochemical staining for p.V600E-mutant BRAF in ameloblastoma epithelium. The staining is cytoplasmic.
Ameloblastoma, conventional. Follicular pattern, with acanthomatous change in the large cyst. Peripheral epithelial cells in the islands have hyperchromatic nuclei in a palisading pattern, reverse polarity, and often cytoplasmic vacuolation.
Ameloblastoma, conventional. High-power view of the follicular pattern showing peripheral ameloblast-like cells with palisaded nuclei, reverse polarity, and cytoplasmic vacuolation; and looser, stellate reticulum–like cells in the centre of the follicles.

Q: The most common activating oncogenic mutation in Conventional Ameloblastoma is the [...] mutation, which can be reliably identified using targeted immunohistochemical stains.
Ameloblastoma, conventional. The most commonly identified oncogenic mutations and their relative frequencies in ameloblastoma (AM) and unicystic ameloblastoma (UAM) located in the mandible or maxilla {24374844; 24993163; 24859340; 30216733}.
Ameloblastoma, conventional. Positive immunohistochemical staining for p.V600E-mutant BRAF in ameloblastoma epithelium. The staining is cytoplasmic.
A: BRAF p.V600E
Back Extra: Conventional Ameloblastoma
- Clinical: Conventional ameloblastomas present as a painless, slow-growing mass that can displace and loosen teeth, expand and perforate the cortices, and cause facial disfigurement.
- Micro: The most common histological subtype of conventional ameloblastoma is the follicular pattern, characterized by islands of epithelium with peripheral ameloblast-like cells and central stellate reticulum-like cells.
- Ancillary: BRAF p.V600E mutations are the most common activating mutations in conventional ameloblastomas, and immunohistochemical staining can be used to detect these mutations.
Reference Gallery:
Ameloblastoma, conventional. Plexiform histological pattern with anastomosing cords and strands of tumour.
Ameloblastoma, conventional. The most commonly identified oncogenic mutations and their relative frequencies in ameloblastoma (AM) and unicystic ameloblastoma (UAM) located in the mandible or maxilla {24374844; 24993163; 24859340; 30216733}.
Ameloblastoma, conventional. Mixed pattern, with larger, rounded, pale-staining areas characteristic of the follicular histological pattern and focally acanthomatous, spiky, darker-staining islands with more cellular central areas, characteristic of the desmoplastic pattern.
Ameloblastoma, conventional. Large ameloblastoma of the mandible, causing facial deformity.
Ameloblastoma, conventional. Panoramic radiograph of an ameloblastoma forming a typical radiolucent, multilocular, soap bubble–pattern lesion with cortical expansion, tooth displacement, and root resorption.
Ameloblastoma, conventional. 3D CT reconstruction highlights expansion and the multilocularity of the tumour.
Ameloblastoma, conventional. Positive immunohistochemical staining for p.V600E-mutant BRAF in ameloblastoma epithelium. The staining is cytoplasmic.
Ameloblastoma, conventional. Follicular pattern, with acanthomatous change in the large cyst. Peripheral epithelial cells in the islands have hyperchromatic nuclei in a palisading pattern, reverse polarity, and often cytoplasmic vacuolation.
Ameloblastoma, conventional. High-power view of the follicular pattern showing peripheral ameloblast-like cells with palisaded nuclei, reverse polarity, and cytoplasmic vacuolation; and looser, stellate reticulum–like cells in the centre of the follicles.

Q: Histologically, Ameloblastoma, extraosseous/peripheral features epithelial islands within the lamina propria that exhibit looser epithelium centrally and [...].
Ameloblastoma, extraosseous. Mucosa with ameloblastic tumour islands within the lamina propria, characterized by hyperchromatic peripheral basal cells and looser epithelium centrally.
A: hyperchromatic peripheral basal cells
Back Extra: Ameloblastoma, extraosseous/peripheral
- Clinical: Ameloblastoma, extraosseous/peripheral is an asymptomatic, slow-growing, firm epulis with a mean diameter of < 20 mm, and a mean patient age of 52 years.
- Micro: Histopathological features include ameloblastic tumour islands characterized by hyperchromatic peripheral basal cells and looser epithelium centrally.
- Ancillary: BRAF p.V600E mutations are commonly found in peripheral ameloblastoma, and BerEP4 expression can help distinguish it from intraoral basal cell carcinoma.
Reference Gallery:
Ameloblastoma, extraosseous. Mucosa with ameloblastic tumour islands within the lamina propria, characterized by hyperchromatic peripheral basal cells and looser epithelium centrally.
Ameloblastoma, extraosseous. A nodule on the gingiva, without radiographic evidence of underlying bone involvement.

Q: Clinically, Ameloblastoma, extraosseous/peripheral typically presents as an asymptomatic, firm nodule (epulis) on the gingiva that distinctly lacks radiographic evidence of [...].
Ameloblastoma, extraosseous. A nodule on the gingiva, without radiographic evidence of underlying bone involvement.
A: underlying bone involvement
Back Extra: Ameloblastoma, extraosseous/peripheral
- Clinical: Ameloblastoma, extraosseous/peripheral is an asymptomatic, slow-growing, firm epulis with a mean diameter of < 20 mm, and a mean patient age of 52 years.
- Micro: Histopathological features include ameloblastic tumour islands characterized by hyperchromatic peripheral basal cells and looser epithelium centrally.
- Ancillary: BRAF p.V600E mutations are commonly found in peripheral ameloblastoma, and BerEP4 expression can help distinguish it from intraoral basal cell carcinoma.
Reference Gallery:
Ameloblastoma, extraosseous. Mucosa with ameloblastic tumour islands within the lamina propria, characterized by hyperchromatic peripheral basal cells and looser epithelium centrally.
Ameloblastoma, extraosseous. A nodule on the gingiva, without radiographic evidence of underlying bone involvement.

Q: Microscopically, the lining epithelium of Unicystic Ameloblastoma is characterized by a palisaded columnar basal layer demonstrating [...] and stellate reticulum-like upper layers.
Ameloblastoma, unicystic. High-power view showing the lining epithelium in one of the zones with elongate or palisaded basal cells, reverse polarity, and cytoplasmic vacuolation. The surface cells, sometimes called “parachute cells” because of their shape, are distinctive. Subepithelial hyalinization in a narrow band is a common finding.
Ameloblastoma, unicystic. Low-power view of the cyst wall, showing regular epithelium that appears to be dyscohesive and no islands in the wall. There is a prominent hyperchromatic basal cell layer, palisaded focally.
A: reverse polarity
Back Extra: Unicystic Ameloblastoma
- Clinical: Unicystic ameloblastoma (UAM) is usually an asymptomatic jaw swelling, often associated with unerupted teeth, especially mandibular third molars.
- Micro: The lining epithelium of UAM is characterized by a palisaded columnar basal layer with reverse polarity and stellate reticulum-like upper layers.
- Ancillary: BRAF p.V600E immunohistochemistry and genetic testing are useful for confirming the diagnosis and predicting recurrence.
Reference Gallery:
Ameloblastoma, unicystic. High-power view showing the lining epithelium in one of the zones with elongate or palisaded basal cells, reverse polarity, and cytoplasmic vacuolation. The surface cells, sometimes called “parachute cells” because of their shape, are distinctive. Subepithelial hyalinization in a narrow band is a common finding.
Ameloblastoma, unicystic. Low-power view of the cyst wall, showing regular epithelium that appears to be dyscohesive and no islands in the wall. There is a prominent hyperchromatic basal cell layer, palisaded focally.
Ameloblastoma, unicystic. Positive cytoplasmic staining for BRAF p.V600E by immunohistochemistry.
Ameloblastoma, unicystic. Part of a panoramic radiograph showing a typical corticated unilocular radiolucency with resorption of roots of the adjacent molar teeth.

Q: Immunohistochemistry and genetic testing for the [...] mutation are frequently positive in Unicystic Ameloblastoma, aiding in diagnosis and predicting recurrence.
Ameloblastoma, unicystic. Positive cytoplasmic staining for BRAF p.V600E by immunohistochemistry.
A: BRAF p.V600E
Back Extra: Unicystic Ameloblastoma
- Clinical: Unicystic ameloblastoma (UAM) is usually an asymptomatic jaw swelling, often associated with unerupted teeth, especially mandibular third molars.
- Micro: The lining epithelium of UAM is characterized by a palisaded columnar basal layer with reverse polarity and stellate reticulum-like upper layers.
- Ancillary: BRAF p.V600E immunohistochemistry and genetic testing are useful for confirming the diagnosis and predicting recurrence.
Reference Gallery:
Ameloblastoma, unicystic. High-power view showing the lining epithelium in one of the zones with elongate or palisaded basal cells, reverse polarity, and cytoplasmic vacuolation. The surface cells, sometimes called “parachute cells” because of their shape, are distinctive. Subepithelial hyalinization in a narrow band is a common finding.
Ameloblastoma, unicystic. Low-power view of the cyst wall, showing regular epithelium that appears to be dyscohesive and no islands in the wall. There is a prominent hyperchromatic basal cell layer, palisaded focally.
Ameloblastoma, unicystic. Positive cytoplasmic staining for BRAF p.V600E by immunohistochemistry.
Ameloblastoma, unicystic. Part of a panoramic radiograph showing a typical corticated unilocular radiolucency with resorption of roots of the adjacent molar teeth.

Q: Radiographically, Unicystic Ameloblastoma typically presents as a corticated [...], often associated with an unerupted mandibular third molar and causing resorption of adjacent roots.
Ameloblastoma, unicystic. Part of a panoramic radiograph showing a typical corticated unilocular radiolucency with resorption of roots of the adjacent molar teeth.
A: unilocular radiolucency
Back Extra: Unicystic Ameloblastoma
- Clinical: Unicystic ameloblastoma (UAM) is usually an asymptomatic jaw swelling, often associated with unerupted teeth, especially mandibular third molars.
- Micro: The lining epithelium of UAM is characterized by a palisaded columnar basal layer with reverse polarity and stellate reticulum-like upper layers.
- Ancillary: BRAF p.V600E immunohistochemistry and genetic testing are useful for confirming the diagnosis and predicting recurrence.
Reference Gallery:
Ameloblastoma, unicystic. High-power view showing the lining epithelium in one of the zones with elongate or palisaded basal cells, reverse polarity, and cytoplasmic vacuolation. The surface cells, sometimes called “parachute cells” because of their shape, are distinctive. Subepithelial hyalinization in a narrow band is a common finding.
Ameloblastoma, unicystic. Low-power view of the cyst wall, showing regular epithelium that appears to be dyscohesive and no islands in the wall. There is a prominent hyperchromatic basal cell layer, palisaded focally.
Ameloblastoma, unicystic. Positive cytoplasmic staining for BRAF p.V600E by immunohistochemistry.
Ameloblastoma, unicystic. Part of a panoramic radiograph showing a typical corticated unilocular radiolucency with resorption of roots of the adjacent molar teeth.

Q: Microscopically, a Calcifying Epithelial Odontogenic Tumor is characterized by nests of polyhedral epithelial cells, focal calcifications, and distinctive extracellular deposits of [...].
Calcifying epithelial odontogenic tumour. Islands of odontogenic epithelium, with amyloid and focal calcification.
Calcifying epithelial odontogenic tumour. High-power view of the epithelial islands, including the polygonal cells, intercellular prickles, and mild nuclear pleomorphism.
Calcifying epithelial odontogenic tumour. Congo red stain demonstrating the amyloid material.
A: amyloid
Back Extra: Calcifying Epithelial Odontogenic Tumour
- Clinical: Many Calcifying Epithelial Odontogenic Tumours are asymptomatic, but larger ones can cause slow-growing jaw expansion and tooth mobility.
- Micro: Characterized by sheets, cords, or nests of polyhedral epithelial cells with amyloid deposits and focal calcification.
- Ancillary: Mutations in PTEN, CDKN2A, JAK3, MET, AMBN, and PTCH1 have been reported in Calcifying Epithelial Odontogenic Tumours.
Reference Gallery:
Calcifying epithelial odontogenic tumour. Islands of odontogenic epithelium, with amyloid and focal calcification.
Calcifying epithelial odontogenic tumour. High-power view of the epithelial islands, including the polygonal cells, intercellular prickles, and mild nuclear pleomorphism.
Calcifying epithelial odontogenic tumour. Congo red stain demonstrating the amyloid material.
Calcifying epithelial odontogenic tumour. Panoramic radiograph showing a calcifying epithelial odontogenic tumour in the left body and parasymphysis of the mandible, generally a well-defined radiolucency with some small internal mineralizations.

Q: A patient presents with a slow-growing jaw expansion. Radiographically, the presence of a well-defined radiolucency with small internal mineralizations is highly characteristic of a [...].
Calcifying epithelial odontogenic tumour. Panoramic radiograph showing a calcifying epithelial odontogenic tumour in the left body and parasymphysis of the mandible, generally a well-defined radiolucency with some small internal mineralizations.
A: Calcifying Epithelial Odontogenic Tumor
Back Extra: Calcifying Epithelial Odontogenic Tumour
- Clinical: Many Calcifying Epithelial Odontogenic Tumours are asymptomatic, but larger ones can cause slow-growing jaw expansion and tooth mobility.
- Micro: Characterized by sheets, cords, or nests of polyhedral epithelial cells with amyloid deposits and focal calcification.
- Ancillary: Mutations in PTEN, CDKN2A, JAK3, MET, AMBN, and PTCH1 have been reported in Calcifying Epithelial Odontogenic Tumours.
Reference Gallery:
Calcifying epithelial odontogenic tumour. Islands of odontogenic epithelium, with amyloid and focal calcification.
Calcifying epithelial odontogenic tumour. High-power view of the epithelial islands, including the polygonal cells, intercellular prickles, and mild nuclear pleomorphism.
Calcifying epithelial odontogenic tumour. Congo red stain demonstrating the amyloid material.
Calcifying epithelial odontogenic tumour. Panoramic radiograph showing a calcifying epithelial odontogenic tumour in the left body and parasymphysis of the mandible, generally a well-defined radiolucency with some small internal mineralizations.

Q: In Metastasizing Ameloblastoma, distant metastatic lesions (such as the brain metastasis shown) exhibit histopathological features that are [...], meaning there are no specific morphologic features that predict metastatic behavior.
Metastasizing ameloblastoma. Brain metastasis from a maxillary ameloblastoma.
A: identical to conventional ameloblastoma
Back Extra: Metastasizing Ameloblastoma
- Clinical: Metastasizing ameloblastoma can present with symptoms such as dry cough, haemoptysis, and dyspnoea, particularly in cases of pulmonary metastasis.
- Micro: Microscopically, metastasizing ameloblastoma exhibits identical histopathological features to conventional ameloblastoma, with no specific features predicting metastasis.
- Ancillary: BRAF p.V600E mutations are commonly found in metastasizing ameloblastoma, but no putative molecular markers of metastatic behavior have been identified.
Reference Gallery:
Metastasizing ameloblastoma. Brain metastasis from a maxillary ameloblastoma.

Q: Histologically, Squamous Odontogenic Tumor consists of islands of benign squamous epithelium with flattened to cuboidal peripheral cells and characteristic central [...].
Squamous odontogenic tumour. Islands of benign squamous epithelium in a mature fibrous stroma.
Squamous odontogenic tumour. The peripheral cells are flattened, and central cells show areas of microcystic degeneration and individual cell keratinization.
A: microcystic degeneration
Back Extra: Squamous Odontogenic Tumour
- Clinical: Squamous Odontogenic Tumour (SOT) usually presents as an asymptomatic swelling, with a mean age at diagnosis of 34.8 years and equal prevalence in men and women.
- Micro: SOT is characterized by islands of benign squamous epithelium in a fibrous stroma, with peripheral cells being flat to cuboidal and central cells showing cystic degeneration and individual cell keratinization.
- Ancillary: NOTCH receptors and their ligands are proposed to play a role in the cytodifferentiation of SOT, and mutations in AMBN have been identified.
Reference Gallery:
Squamous odontogenic tumour. Islands of benign squamous epithelium in a mature fibrous stroma.
Squamous odontogenic tumour. The peripheral cells are flattened, and central cells show areas of microcystic degeneration and individual cell keratinization.
Squamous odontogenic tumour-like proliferation in the wall of an odontogenic cyst. Proliferation of epithelium in the wall of an odontogenic cyst can be a close mimic for squamous odontogenic tumour, but the context is not compatible with that diagnosis.
Squamous odontogenic tumour-like proliferation in the wall of an odontogenic cyst. Proliferation of epithelium in the wall of an odontogenic cyst can be a close mimic for squamous odontogenic tumour, but the context is not compatible with that diagnosis.

Q: When evaluating a suspected Squamous Odontogenic Tumor, pathologists must exclude a reactive SOT-like epithelial proliferation occurring in the wall of a(n) [...], which can be a close morphological mimic.
Squamous odontogenic tumour-like proliferation in the wall of an odontogenic cyst. Proliferation of epithelium in the wall of an odontogenic cyst can be a close mimic for squamous odontogenic tumour, but the context is not compatible with that diagnosis.
Squamous odontogenic tumour-like proliferation in the wall of an odontogenic cyst. Proliferation of epithelium in the wall of an odontogenic cyst can be a close mimic for squamous odontogenic tumour, but the context is not compatible with that diagnosis.
A: odontogenic cyst
Back Extra: Squamous Odontogenic Tumour
- Clinical: Squamous Odontogenic Tumour (SOT) usually presents as an asymptomatic swelling, with a mean age at diagnosis of 34.8 years and equal prevalence in men and women.
- Micro: SOT is characterized by islands of benign squamous epithelium in a fibrous stroma, with peripheral cells being flat to cuboidal and central cells showing cystic degeneration and individual cell keratinization.
- Ancillary: NOTCH receptors and their ligands are proposed to play a role in the cytodifferentiation of SOT, and mutations in AMBN have been identified.
Reference Gallery:
Squamous odontogenic tumour. Islands of benign squamous epithelium in a mature fibrous stroma.
Squamous odontogenic tumour. The peripheral cells are flattened, and central cells show areas of microcystic degeneration and individual cell keratinization.
Squamous odontogenic tumour-like proliferation in the wall of an odontogenic cyst. Proliferation of epithelium in the wall of an odontogenic cyst can be a close mimic for squamous odontogenic tumour, but the context is not compatible with that diagnosis.
Squamous odontogenic tumour-like proliferation in the wall of an odontogenic cyst. Proliferation of epithelium in the wall of an odontogenic cyst can be a close mimic for squamous odontogenic tumour, but the context is not compatible with that diagnosis.

Q: Histologically, cemento-ossifying fibroma exhibits a variable fibrous stroma containing a mixture of mineralized tissue, including woven bone, lamellar bone, and characteristic [...] calcifications.
Cemento-ossifying fibroma. Well-defined tumour mass with cellular fibrous stroma and focal cementum-like dense bone calcifications. This particular example shows abundant stroma and only a focal mineralized component.
Cemento-ossifying fibroma. A lesion in mid-phase maturation, with less-cellular fibrous stroma and dense lamellar bone mineralization.
Cemento-ossifying fibroma. Trabeculae of heavily mineralized but sparsely cellular woven bone in a fibrous stroma.
A: cementum-like
Back Extra: Cemento-ossifying fibroma
- Clinical: Cemento-ossifying fibroma typically causes painless jaw expansion and may present as a well-defined corticated radiolucency on imaging.
- Micro: Histologically, cemento-ossifying fibroma shows a variable mix of fibrous stroma and mineralized tissue, including woven and lamellar bone, and cementum-like calcifications.
- Ancillary: Inactivating mutations in the CDC73 (HRPT2) gene have been identified in some cases of cemento-ossifying fibroma.
Reference Gallery:
Cemento-ossifying fibroma. Well-defined tumour mass with cellular fibrous stroma and focal cementum-like dense bone calcifications. This particular example shows abundant stroma and only a focal mineralized component.
Cemento-ossifying fibroma. Panoramic radiograph showing a well-defined, expansile radiolucency in the posterior mandible with associated cortical thinning and tooth root displacement.
Cemento-ossifying fibroma. A lesion in mid-phase maturation, with less-cellular fibrous stroma and dense lamellar bone mineralization.
Cemento-ossifying fibroma. Trabeculae of heavily mineralized but sparsely cellular woven bone in a fibrous stroma.

Q: Imaging of a cemento-ossifying fibroma typically reveals a well-defined, expansile [...] in the posterior mandible, which can cause cortical thinning and displacement of tooth roots.
Cemento-ossifying fibroma. Panoramic radiograph showing a well-defined, expansile radiolucency in the posterior mandible with associated cortical thinning and tooth root displacement.
A: radiolucency
Back Extra: Cemento-ossifying fibroma
- Clinical: Cemento-ossifying fibroma typically causes painless jaw expansion and may present as a well-defined corticated radiolucency on imaging.
- Micro: Histologically, cemento-ossifying fibroma shows a variable mix of fibrous stroma and mineralized tissue, including woven and lamellar bone, and cementum-like calcifications.
- Ancillary: Inactivating mutations in the CDC73 (HRPT2) gene have been identified in some cases of cemento-ossifying fibroma.
Reference Gallery:
Cemento-ossifying fibroma. Well-defined tumour mass with cellular fibrous stroma and focal cementum-like dense bone calcifications. This particular example shows abundant stroma and only a focal mineralized component.
Cemento-ossifying fibroma. Panoramic radiograph showing a well-defined, expansile radiolucency in the posterior mandible with associated cortical thinning and tooth root displacement.
Cemento-ossifying fibroma. A lesion in mid-phase maturation, with less-cellular fibrous stroma and dense lamellar bone mineralization.
Cemento-ossifying fibroma. Trabeculae of heavily mineralized but sparsely cellular woven bone in a fibrous stroma.

Q: Radiographically, a Cementoblastoma characteristically presents as a radiopaque mass attached to the tooth root, typically surrounded by a [...] continuous with the periodontal ligament.
Cementoblastoma. Panoramic radiograph showing a cementoblastoma attached to the root of the first permanent molar, a typical radiopaque lesion with a radiolucent rim in continuity with the periodontal ligament.
A: radiolucent rim
Back Extra: Cementoblastoma
- Clinical: Cementoblastoma (CB) causes a slow-growing, characteristically painful expansion of the jaw, with the associated tooth remaining vital in about 80% of cases.
- Micro: Histologically, CB resembles osteoblastoma, with a dense cellular cementum mass fused with the resorbed tooth root, and radiating finger-like trabeculae of newly formed matrix at the periphery.
- Ancillary: CB harbours FOS rearrangement and shows FOS overexpression, similar to osteoid osteoma and osteoblastoma.
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Cementoblastoma. A low-power photomicrograph showing a cementoblastoma arising from and fused to a resorbed tooth root.
Cementoblastoma. Buccal and lingual expansion in a patient with a cementoblastoma affecting the mandibular first molar tooth.
Cementoblastoma. Panoramic radiograph showing a cementoblastoma attached to the root of the first permanent molar, a typical radiopaque lesion with a radiolucent rim in continuity with the periodontal ligament.
Cementoblastoma. Dense bone showing prominent resting and reversal lines with small medullary spaces partly or completely filled by multilayered eosinophilic and slightly enlarged osteoblasts.

Q: A defining histologic and clinical feature of Cementoblastoma is a dense mass of cellular cementum that is directly [...] to the resorbed root of the associated tooth.
Cementoblastoma. A low-power photomicrograph showing a cementoblastoma arising from and fused to a resorbed tooth root.
Cementoblastoma. Buccal and lingual expansion in a patient with a cementoblastoma affecting the mandibular first molar tooth.
A: fused
Back Extra: Cementoblastoma
- Clinical: Cementoblastoma (CB) causes a slow-growing, characteristically painful expansion of the jaw, with the associated tooth remaining vital in about 80% of cases.
- Micro: Histologically, CB resembles osteoblastoma, with a dense cellular cementum mass fused with the resorbed tooth root, and radiating finger-like trabeculae of newly formed matrix at the periphery.
- Ancillary: CB harbours FOS rearrangement and shows FOS overexpression, similar to osteoid osteoma and osteoblastoma.
Reference Gallery:
Cementoblastoma. A low-power photomicrograph showing a cementoblastoma arising from and fused to a resorbed tooth root.
Cementoblastoma. Buccal and lingual expansion in a patient with a cementoblastoma affecting the mandibular first molar tooth.
Cementoblastoma. Panoramic radiograph showing a cementoblastoma attached to the root of the first permanent molar, a typical radiopaque lesion with a radiolucent rim in continuity with the periodontal ligament.
Cementoblastoma. Dense bone showing prominent resting and reversal lines with small medullary spaces partly or completely filled by multilayered eosinophilic and slightly enlarged osteoblasts.

Q: Microscopically, the dense matrix of a Cementoblastoma contains small medullary spaces lined by multilayered osteoblast-like cells and exhibits prominent [...].
Cementoblastoma. Dense bone showing prominent resting and reversal lines with small medullary spaces partly or completely filled by multilayered eosinophilic and slightly enlarged osteoblasts.
A: resting and reversal lines
Back Extra: Cementoblastoma
- Clinical: Cementoblastoma (CB) causes a slow-growing, characteristically painful expansion of the jaw, with the associated tooth remaining vital in about 80% of cases.
- Micro: Histologically, CB resembles osteoblastoma, with a dense cellular cementum mass fused with the resorbed tooth root, and radiating finger-like trabeculae of newly formed matrix at the periphery.
- Ancillary: CB harbours FOS rearrangement and shows FOS overexpression, similar to osteoid osteoma and osteoblastoma.
Reference Gallery:
Cementoblastoma. A low-power photomicrograph showing a cementoblastoma arising from and fused to a resorbed tooth root.
Cementoblastoma. Buccal and lingual expansion in a patient with a cementoblastoma affecting the mandibular first molar tooth.
Cementoblastoma. Panoramic radiograph showing a cementoblastoma attached to the root of the first permanent molar, a typical radiopaque lesion with a radiolucent rim in continuity with the periodontal ligament.
Cementoblastoma. Dense bone showing prominent resting and reversal lines with small medullary spaces partly or completely filled by multilayered eosinophilic and slightly enlarged osteoblasts.

Q: The classic histologic presentation of an Odontogenic Fibroma consists of moderately cellular, bland fibrous tissue containing inactive-appearing nests and cords of [...].
Central odontogenic fibroma. Appearance of the conventional pattern, cellular connective tissue associated with strands of odontogenic epithelium.
A: odontogenic epithelium
Back Extra: Odontogenic Fibroma
- Clinical: Small odontogenic fibromas are usually asymptomatic, while larger tumors can cause localized swelling, tooth loosening, and pain.
- Micro: Odontogenic fibromas are characterized by moderately cellular, bland fibrous tissue with inactive-appearing odontogenic epithelial nests and cords, sometimes with minor hard tissue formation.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis and management of odontogenic fibromas.
Reference Gallery:
Central odontogenic fibroma. Appearance of the conventional pattern, cellular connective tissue associated with strands of odontogenic epithelium.
Central odontogenic fibroma, amyloid subtype. Fibrous tissue with scattered odontogenic epithelial islands associated with amyloid deposits presenting as homogeneous eosinophilic ovoid masses.
Odontogenic fibroma, granular cell pattern. Granular stromal cells associated with odontogenic epithelial islands.
Central odontogenic fibroma. A well-defined, partly corticated radiolucency with areas of radiopacity in the left mandibular body, with tooth displacement.

Q: A well-defined, partly corticated radiolucency with areas of radiopacity causing tooth displacement is the characteristic radiographic presentation of a large central [...].
Central odontogenic fibroma. A well-defined, partly corticated radiolucency with areas of radiopacity in the left mandibular body, with tooth displacement.
A: Odontogenic Fibroma
Back Extra: Odontogenic Fibroma
- Clinical: Small odontogenic fibromas are usually asymptomatic, while larger tumors can cause localized swelling, tooth loosening, and pain.
- Micro: Odontogenic fibromas are characterized by moderately cellular, bland fibrous tissue with inactive-appearing odontogenic epithelial nests and cords, sometimes with minor hard tissue formation.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis and management of odontogenic fibromas.
Reference Gallery:
Central odontogenic fibroma. Appearance of the conventional pattern, cellular connective tissue associated with strands of odontogenic epithelium.
Central odontogenic fibroma, amyloid subtype. Fibrous tissue with scattered odontogenic epithelial islands associated with amyloid deposits presenting as homogeneous eosinophilic ovoid masses.
Odontogenic fibroma, granular cell pattern. Granular stromal cells associated with odontogenic epithelial islands.
Central odontogenic fibroma. A well-defined, partly corticated radiolucency with areas of radiopacity in the left mandibular body, with tooth displacement.

Q: Microscopic variants of an Odontogenic Fibroma include a granular cell pattern and an [...] subtype, the latter being characterized by homogeneous eosinophilic ovoid deposits among epithelial islands.
Central odontogenic fibroma, amyloid subtype. Fibrous tissue with scattered odontogenic epithelial islands associated with amyloid deposits presenting as homogeneous eosinophilic ovoid masses.
Odontogenic fibroma, granular cell pattern. Granular stromal cells associated with odontogenic epithelial islands.
A: amyloid
Back Extra: Odontogenic Fibroma
- Clinical: Small odontogenic fibromas are usually asymptomatic, while larger tumors can cause localized swelling, tooth loosening, and pain.
- Micro: Odontogenic fibromas are characterized by moderately cellular, bland fibrous tissue with inactive-appearing odontogenic epithelial nests and cords, sometimes with minor hard tissue formation.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis and management of odontogenic fibromas.
Reference Gallery:
Central odontogenic fibroma. Appearance of the conventional pattern, cellular connective tissue associated with strands of odontogenic epithelium.
Central odontogenic fibroma, amyloid subtype. Fibrous tissue with scattered odontogenic epithelial islands associated with amyloid deposits presenting as homogeneous eosinophilic ovoid masses.
Odontogenic fibroma, granular cell pattern. Granular stromal cells associated with odontogenic epithelial islands.
Central odontogenic fibroma. A well-defined, partly corticated radiolucency with areas of radiopacity in the left mandibular body, with tooth displacement.

Q: Radiographically, an odontogenic myxoma frequently presents as a unilocular or multilocular radiolucency with characteristic fine, straight internal [...] (bony septa).
Odontogenic myxoma. This deliberately slightly underexposed panoramic radiograph shows the characteristic straight criss-crossing internal bony septa found in some lesions.
Odontogenic myxoma. This example in the body of the mandible shows thin, expanded cortex and bony septa in the CT bone window.
A: trabeculation
Back Extra: Odontogenic Myxoma
- Clinical: Odontogenic myxoma (OM) presents with insidious, slow growth and bone expansion, often causing tooth mobility or displacement.
- Micro: Histologically, OM is characterized by a sparse population of stellate to spindle cells in a loose myxoid stroma.
- Ancillary: Radiographically, OM often appears as unilocular or multilocular radiolucencies with fine, straight internal trabeculation.
Reference Gallery:
Normal dental follicle resembling odontogenic myxoma. Histologically, dental follicle and papilla are almost identical to odontogenic myxoma, but a clue may be given by the size, shape, and presence of epithelial remnants running along some surfaces.
Odontogenic myxoma. This deliberately slightly underexposed panoramic radiograph shows the characteristic straight criss-crossing internal bony septa found in some lesions.
Odontogenic myxoma. An odontogenic myxoma from the mandible, comprising loose myxoid tissue with a sparse cell population.
Odontogenic myxoma. High-magnification view of an odontogenic myxoma from the mandible, showing loose myxoid tissue stroma with scattered spindle and stellate cells without atypia and forming minimal or no collagen.
Odontogenic myxoma. This myxoma has prominent collagen formation, but excess basophilic ground substance remains between the fibres. Such lesions are sometimes termed “fibromyxoma”.
Odontogenic myxoma. This example in the body of the mandible shows thin, expanded cortex and bony septa in the CT bone window.
Odontogenic myxoma. This example in the body of the mandible shows low soft tissue density.
Odontogenic myxoma. An example in the body of the mandible. The high proton density resulting from the high water content in the myxoid tissue gives a hyperintense signal on T2-weighted MRI.

Q: Histologically, an odontogenic myxoma is characterized by a sparse population of bland stellate to spindle cells suspended in an abundant, loose [...].
Odontogenic myxoma. An odontogenic myxoma from the mandible, comprising loose myxoid tissue with a sparse cell population.
Odontogenic myxoma. High-magnification view of an odontogenic myxoma from the mandible, showing loose myxoid tissue stroma with scattered spindle and stellate cells without atypia and forming minimal or no collagen.
A: myxoid stroma
Back Extra: Odontogenic Myxoma
- Clinical: Odontogenic myxoma (OM) presents with insidious, slow growth and bone expansion, often causing tooth mobility or displacement.
- Micro: Histologically, OM is characterized by a sparse population of stellate to spindle cells in a loose myxoid stroma.
- Ancillary: Radiographically, OM often appears as unilocular or multilocular radiolucencies with fine, straight internal trabeculation.
Reference Gallery:
Normal dental follicle resembling odontogenic myxoma. Histologically, dental follicle and papilla are almost identical to odontogenic myxoma, but a clue may be given by the size, shape, and presence of epithelial remnants running along some surfaces.
Odontogenic myxoma. This deliberately slightly underexposed panoramic radiograph shows the characteristic straight criss-crossing internal bony septa found in some lesions.
Odontogenic myxoma. An odontogenic myxoma from the mandible, comprising loose myxoid tissue with a sparse cell population.
Odontogenic myxoma. High-magnification view of an odontogenic myxoma from the mandible, showing loose myxoid tissue stroma with scattered spindle and stellate cells without atypia and forming minimal or no collagen.
Odontogenic myxoma. This myxoma has prominent collagen formation, but excess basophilic ground substance remains between the fibres. Such lesions are sometimes termed “fibromyxoma”.
Odontogenic myxoma. This example in the body of the mandible shows thin, expanded cortex and bony septa in the CT bone window.
Odontogenic myxoma. This example in the body of the mandible shows low soft tissue density.
Odontogenic myxoma. An example in the body of the mandible. The high proton density resulting from the high water content in the myxoid tissue gives a hyperintense signal on T2-weighted MRI.

Q: Histologically, the loose connective tissue of an odontogenic myxoma can nearly identically mimic a normal [...], although the latter may contain characteristic epithelial remnants along its surfaces.
Normal dental follicle resembling odontogenic myxoma. Histologically, dental follicle and papilla are almost identical to odontogenic myxoma, but a clue may be given by the size, shape, and presence of epithelial remnants running along some surfaces.
Odontogenic myxoma. High-magnification view of an odontogenic myxoma from the mandible, showing loose myxoid tissue stroma with scattered spindle and stellate cells without atypia and forming minimal or no collagen.
A: dental follicle
Back Extra: Odontogenic Myxoma
- Clinical: Odontogenic myxoma (OM) presents with insidious, slow growth and bone expansion, often causing tooth mobility or displacement.
- Micro: Histologically, OM is characterized by a sparse population of stellate to spindle cells in a loose myxoid stroma.
- Ancillary: Radiographically, OM often appears as unilocular or multilocular radiolucencies with fine, straight internal trabeculation.
Reference Gallery:
Normal dental follicle resembling odontogenic myxoma. Histologically, dental follicle and papilla are almost identical to odontogenic myxoma, but a clue may be given by the size, shape, and presence of epithelial remnants running along some surfaces.
Odontogenic myxoma. This deliberately slightly underexposed panoramic radiograph shows the characteristic straight criss-crossing internal bony septa found in some lesions.
Odontogenic myxoma. An odontogenic myxoma from the mandible, comprising loose myxoid tissue with a sparse cell population.
Odontogenic myxoma. High-magnification view of an odontogenic myxoma from the mandible, showing loose myxoid tissue stroma with scattered spindle and stellate cells without atypia and forming minimal or no collagen.
Odontogenic myxoma. This myxoma has prominent collagen formation, but excess basophilic ground substance remains between the fibres. Such lesions are sometimes termed “fibromyxoma”.
Odontogenic myxoma. This example in the body of the mandible shows thin, expanded cortex and bony septa in the CT bone window.
Odontogenic myxoma. This example in the body of the mandible shows low soft tissue density.
Odontogenic myxoma. An example in the body of the mandible. The high proton density resulting from the high water content in the myxoid tissue gives a hyperintense signal on T2-weighted MRI.

Q: Microscopically, Ameloblastic Fibroma is a biphasic tumor characterized by bilayered strands of ameloblast-like epithelium set in a hypercellular primitive stroma that characteristically resembles [...].
Ameloblastic fibroma. Ameloblast-like epithelial cells with tall, hyperchromatic, palisading nuclei with reverse polarity arranged in bilayered, parallel strands in a hypercellular stroma that resembles dental papilla.
Ameloblastic fibroma. Some of the epithelial strands widen into rounded expansions, the larger of which may contain a small amount of loose, stellate reticulum–like epithelium. Occasionally, if these enlargements are wide enough, they resemble an early enamel organ.
A: dental papilla
Back Extra: Ameloblastic Fibroma
- Clinical: Most Ameloblastic Fibromas (78%) are slow-growing and cause asymptomatic jawbone expansion. They are often associated with unerupted and displaced teeth, particularly the first or second permanent molars.
- Micro: The mesenchymal component of Ameloblastic Fibroma resembles dental papilla, and the epithelial component forms long, narrow cords and strands of bilaminar cuboidal to columnar palisaded cells, with occasional thickenings.
- Ancillary: BRAF p.V600E mutations are detected in 46% of cases, mostly in the mesenchymal component, and can be useful for excluding developing odontomas in selected cases.
Reference Gallery:
Ameloblastic fibroma. Ameloblast-like epithelial cells with tall, hyperchromatic, palisading nuclei with reverse polarity arranged in bilayered, parallel strands in a hypercellular stroma that resembles dental papilla.
Ameloblastic fibroma. Some of the epithelial strands widen into rounded expansions, the larger of which may contain a small amount of loose, stellate reticulum–like epithelium. Occasionally, if these enlargements are wide enough, they resemble an early enamel organ.
Ameloblastic fibroma. Cone-beam CT, axial plane, showing a multilocular, hypodense tumour of the left maxilla with prominent expansion, cortical thinning, and tooth root displacement.
Ameloblastic fibroma. Cone-beam CT, coronal plane, showing a multilocular, hypodense tumour of the left maxilla with prominent expansion, cortical thinning, and tooth root displacement.

Q: A slow-growing jaw tumor presents radiographically as a multilocular, hypodense expansion that is often associated with an unerupted tooth; when biopsy reveals narrow cords of palisaded epithelial cells within a primitive stroma, the diagnosis is [...].
Ameloblastic fibroma. Ameloblast-like epithelial cells with tall, hyperchromatic, palisading nuclei with reverse polarity arranged in bilayered, parallel strands in a hypercellular stroma that resembles dental papilla.
Ameloblastic fibroma. Cone-beam CT, axial plane, showing a multilocular, hypodense tumour of the left maxilla with prominent expansion, cortical thinning, and tooth root displacement.
Ameloblastic fibroma. Cone-beam CT, coronal plane, showing a multilocular, hypodense tumour of the left maxilla with prominent expansion, cortical thinning, and tooth root displacement.
A: Ameloblastic Fibroma
Back Extra: Ameloblastic Fibroma
- Clinical: Most Ameloblastic Fibromas (78%) are slow-growing and cause asymptomatic jawbone expansion. They are often associated with unerupted and displaced teeth, particularly the first or second permanent molars.
- Micro: The mesenchymal component of Ameloblastic Fibroma resembles dental papilla, and the epithelial component forms long, narrow cords and strands of bilaminar cuboidal to columnar palisaded cells, with occasional thickenings.
- Ancillary: BRAF p.V600E mutations are detected in 46% of cases, mostly in the mesenchymal component, and can be useful for excluding developing odontomas in selected cases.
Reference Gallery:
Ameloblastic fibroma. Ameloblast-like epithelial cells with tall, hyperchromatic, palisading nuclei with reverse polarity arranged in bilayered, parallel strands in a hypercellular stroma that resembles dental papilla.
Ameloblastic fibroma. Some of the epithelial strands widen into rounded expansions, the larger of which may contain a small amount of loose, stellate reticulum–like epithelium. Occasionally, if these enlargements are wide enough, they resemble an early enamel organ.
Ameloblastic fibroma. Cone-beam CT, axial plane, showing a multilocular, hypodense tumour of the left maxilla with prominent expansion, cortical thinning, and tooth root displacement.
Ameloblastic fibroma. Cone-beam CT, coronal plane, showing a multilocular, hypodense tumour of the left maxilla with prominent expansion, cortical thinning, and tooth root displacement.

Q: Histologically, the Dentinogenic ghost cell tumor is characterized by nests of ameloblastoma-like epithelium with varying amounts of dentinoid and prominent [...] keratinization.
Dentinogenic ghost cell tumour. An ameloblastoma-like epithelial proliferation with ghost cells entrapped within masses of dentinoid. Aggregates of ghost cells devoid of epithelium are being integrated within the dentinoid.
Dentinogenic ghost cell tumour. Large aggregates of flattened, pale eosinophilic ghost cells surrounded by a thin hyperchromatic epithelium resembling ameloblastoma.
A: ghost cell
Back Extra: Dentinogenic ghost cell tumour
- Clinical: Dentinogenic ghost cell tumour presents as a slow-growing tumour with cortical expansion and occasional cortical perforation, often causing facial asymmetry.
- Micro: The tumour is characterized by nests and islands of ameloblastoma-like epithelium with prominent ghost cell keratinization and varying amounts of dentinoid.
- Ancillary: BRAF p.V600E mutations are absent in Dentinogenic ghost cell tumours, but CTNNB1 mutations may be associated with ghost cell keratinization.
Reference Gallery:
Dentinogenic ghost cell tumour. Intraoral view of the patient in Fig. 28378 shows the tumour with gross cortical bone expansion.
Dentinogenic ghost cell tumour. Panoramic radiograph from the patient in Fig. 28378, showing a markedly expansile multilocular lesion with cortical thinning, partial cortication, and multiple internal radiopacities in the body and anterior mandible.
Dentinogenic ghost cell tumour. An ameloblastoma-like epithelial proliferation with ghost cells entrapped within masses of dentinoid. Aggregates of ghost cells devoid of epithelium are being integrated within the dentinoid.
Dentinogenic ghost cell tumour. Large aggregates of flattened, pale eosinophilic ghost cells surrounded by a thin hyperchromatic epithelium resembling ameloblastoma.
Dentinogenic ghost cell tumour. A 59-year-old woman with an anterior mandibular tumour, showing facial asymmetry.

Q: While it features ameloblastoma-like epithelium, the Dentinogenic ghost cell tumor lacks BRAF p.V600E mutations; instead, ghost cell keratinization in this lesion is typically associated with mutations in the [...] gene.
Dentinogenic ghost cell tumour. Large aggregates of flattened, pale eosinophilic ghost cells surrounded by a thin hyperchromatic epithelium resembling ameloblastoma.
A: CTNNB1
Back Extra: Dentinogenic ghost cell tumour
- Clinical: Dentinogenic ghost cell tumour presents as a slow-growing tumour with cortical expansion and occasional cortical perforation, often causing facial asymmetry.
- Micro: The tumour is characterized by nests and islands of ameloblastoma-like epithelium with prominent ghost cell keratinization and varying amounts of dentinoid.
- Ancillary: BRAF p.V600E mutations are absent in Dentinogenic ghost cell tumours, but CTNNB1 mutations may be associated with ghost cell keratinization.
Reference Gallery:
Dentinogenic ghost cell tumour. Intraoral view of the patient in Fig. 28378 shows the tumour with gross cortical bone expansion.
Dentinogenic ghost cell tumour. Panoramic radiograph from the patient in Fig. 28378, showing a markedly expansile multilocular lesion with cortical thinning, partial cortication, and multiple internal radiopacities in the body and anterior mandible.
Dentinogenic ghost cell tumour. An ameloblastoma-like epithelial proliferation with ghost cells entrapped within masses of dentinoid. Aggregates of ghost cells devoid of epithelium are being integrated within the dentinoid.
Dentinogenic ghost cell tumour. Large aggregates of flattened, pale eosinophilic ghost cells surrounded by a thin hyperchromatic epithelium resembling ameloblastoma.
Dentinogenic ghost cell tumour. A 59-year-old woman with an anterior mandibular tumour, showing facial asymmetry.

Q: A slow-growing, markedly expansile multilocular lesion of the jaw with internal radiopacities that microscopically shows dentinoid and anucleate pale eosinophilic cells is best diagnosed as a [...].
Dentinogenic ghost cell tumour. Panoramic radiograph from the patient in Fig. 28378, showing a markedly expansile multilocular lesion with cortical thinning, partial cortication, and multiple internal radiopacities in the body and anterior mandible.
Dentinogenic ghost cell tumour. An ameloblastoma-like epithelial proliferation with ghost cells entrapped within masses of dentinoid. Aggregates of ghost cells devoid of epithelium are being integrated within the dentinoid.
A: Dentinogenic ghost cell tumor
Back Extra: Dentinogenic ghost cell tumour
- Clinical: Dentinogenic ghost cell tumour presents as a slow-growing tumour with cortical expansion and occasional cortical perforation, often causing facial asymmetry.
- Micro: The tumour is characterized by nests and islands of ameloblastoma-like epithelium with prominent ghost cell keratinization and varying amounts of dentinoid.
- Ancillary: BRAF p.V600E mutations are absent in Dentinogenic ghost cell tumours, but CTNNB1 mutations may be associated with ghost cell keratinization.
Reference Gallery:
Dentinogenic ghost cell tumour. Intraoral view of the patient in Fig. 28378 shows the tumour with gross cortical bone expansion.
Dentinogenic ghost cell tumour. Panoramic radiograph from the patient in Fig. 28378, showing a markedly expansile multilocular lesion with cortical thinning, partial cortication, and multiple internal radiopacities in the body and anterior mandible.
Dentinogenic ghost cell tumour. An ameloblastoma-like epithelial proliferation with ghost cells entrapped within masses of dentinoid. Aggregates of ghost cells devoid of epithelium are being integrated within the dentinoid.
Dentinogenic ghost cell tumour. Large aggregates of flattened, pale eosinophilic ghost cells surrounded by a thin hyperchromatic epithelium resembling ameloblastoma.
Dentinogenic ghost cell tumour. A 59-year-old woman with an anterior mandibular tumour, showing facial asymmetry.

Q: The compound subtype of Odontoma is morphologically characterized by a conglomerate of multiple small, rudimentary [...].
Odontoma. Compound subtype. Microscopic view of multiple small, tooth-like structures.
Odontoma. Compound subtype. Macroscopic view showing a conglomerate of numerous small, rudimentary tooth-like structures.
Odontoma. Compound subtype. Cropped panoramic radiograph showing a mass composed of several small, radi opaque tooth-like structures, displacing the first maxillary premolar upwards.
A: tooth-like structures
Back Extra: Odontoma
- Clinical: Odontomas are asymptomatic, slow-growing lesions often associated with unerupted teeth, typically 10-30 mm in diameter.
- Micro: Compound odontomas contain multiple rudimentary teeth with dentine and enamel matrix, while complex odontomas show a disorganized mass of mature tubular dentine and rounded zones of enamel matrix.
- Ancillary: No specific ancillary studies are required for the diagnosis of odontomas.
Reference Gallery:
Odontoma. Compound subtype. Microscopic view of multiple small, tooth-like structures.
Odontoma. Complex subtype. Microscopic section showing radiating sheets of dentine enclosing spaces containing enamel matrix where mature enamel has been removed by decalcification.
Odontoma. Complex odontoma at high magnification, highlighting the keyhole spaces containing basophilic enamel matrix, which has a prismatic structure. Residual odontogenic epithelium is also present around matrix.
Odontoma. Compound subtype. Macroscopic view showing a conglomerate of numerous small, rudimentary tooth-like structures.
Odontoma. Compound subtype. Cropped panoramic radiograph showing a mass composed of several small, radi opaque tooth-like structures, displacing the first maxillary premolar upwards.
Odontoma. Complex subtype. Cropped panoramic radiograph showing a well-defined radiopaque mass associated with the mandibular third molar, which was displaced downwards to the lower border of the mandible with the inferior alveolar nerve canal.

Q: Unlike the compound variant, the complex subtype of Odontoma microscopically presents as a disorganized mass of mature tubular [...] and rounded zones of basophilic enamel matrix.
Odontoma. Complex subtype. Microscopic section showing radiating sheets of dentine enclosing spaces containing enamel matrix where mature enamel has been removed by decalcification.
Odontoma. Complex odontoma at high magnification, highlighting the keyhole spaces containing basophilic enamel matrix, which has a prismatic structure. Residual odontogenic epithelium is also present around matrix.
A: dentin
Back Extra: Odontoma
- Clinical: Odontomas are asymptomatic, slow-growing lesions often associated with unerupted teeth, typically 10-30 mm in diameter.
- Micro: Compound odontomas contain multiple rudimentary teeth with dentine and enamel matrix, while complex odontomas show a disorganized mass of mature tubular dentine and rounded zones of enamel matrix.
- Ancillary: No specific ancillary studies are required for the diagnosis of odontomas.
Reference Gallery:
Odontoma. Compound subtype. Microscopic view of multiple small, tooth-like structures.
Odontoma. Complex subtype. Microscopic section showing radiating sheets of dentine enclosing spaces containing enamel matrix where mature enamel has been removed by decalcification.
Odontoma. Complex odontoma at high magnification, highlighting the keyhole spaces containing basophilic enamel matrix, which has a prismatic structure. Residual odontogenic epithelium is also present around matrix.
Odontoma. Compound subtype. Macroscopic view showing a conglomerate of numerous small, rudimentary tooth-like structures.
Odontoma. Compound subtype. Cropped panoramic radiograph showing a mass composed of several small, radi opaque tooth-like structures, displacing the first maxillary premolar upwards.
Odontoma. Complex subtype. Cropped panoramic radiograph showing a well-defined radiopaque mass associated with the mandibular third molar, which was displaced downwards to the lower border of the mandible with the inferior alveolar nerve canal.

Q: Radiographically, an Odontoma typically presents as an asymptomatic, well-defined radiopaque mass that is frequently associated with an [...] tooth.
Odontoma. Compound subtype. Cropped panoramic radiograph showing a mass composed of several small, radi opaque tooth-like structures, displacing the first maxillary premolar upwards.
Odontoma. Complex subtype. Cropped panoramic radiograph showing a well-defined radiopaque mass associated with the mandibular third molar, which was displaced downwards to the lower border of the mandible with the inferior alveolar nerve canal.
A: unerupted
Back Extra: Odontoma
- Clinical: Odontomas are asymptomatic, slow-growing lesions often associated with unerupted teeth, typically 10-30 mm in diameter.
- Micro: Compound odontomas contain multiple rudimentary teeth with dentine and enamel matrix, while complex odontomas show a disorganized mass of mature tubular dentine and rounded zones of enamel matrix.
- Ancillary: No specific ancillary studies are required for the diagnosis of odontomas.
Reference Gallery:
Odontoma. Compound subtype. Microscopic view of multiple small, tooth-like structures.
Odontoma. Complex subtype. Microscopic section showing radiating sheets of dentine enclosing spaces containing enamel matrix where mature enamel has been removed by decalcification.
Odontoma. Complex odontoma at high magnification, highlighting the keyhole spaces containing basophilic enamel matrix, which has a prismatic structure. Residual odontogenic epithelium is also present around matrix.
Odontoma. Compound subtype. Macroscopic view showing a conglomerate of numerous small, rudimentary tooth-like structures.
Odontoma. Compound subtype. Cropped panoramic radiograph showing a mass composed of several small, radi opaque tooth-like structures, displacing the first maxillary premolar upwards.
Odontoma. Complex subtype. Cropped panoramic radiograph showing a well-defined radiopaque mass associated with the mandibular third molar, which was displaced downwards to the lower border of the mandible with the inferior alveolar nerve canal.

Q: Radiographically, Primordial Odontogenic Tumor typically presents as a well-defined unilocular radiolucency that displaces adjacent roots and is closely associated with an [...] tooth.
Primordial odontogenic tumour. A well-defined unilocular radiolucency surrounding and displacing the second premolar and producing slight root resorption of the first permanent molar.
Primordial odontogenic tumour. Macroscopic appearance. A solid, white mass displacing the enclosed molar towards the periphery, visible just below the surface centrally, and closely associated with two further teeth.
A: unerupted
Back Extra: Primordial Odontogenic Tumour
- Clinical: Primordial odontogenic tumour (POT) usually presents as a well-defined radiolucency associated with unerupted teeth, most commonly the mandibular third molar, and may displace and resorb roots of adjacent teeth.
- Micro: POT is characterized by loose or myxoid fibrous tissue containing variable numbers of fusiform and stellate fibroblasts, surrounded by a single layer of columnar or cuboidal epithelium with scant superficial layers of stellate reticulum-like cells.
- Ancillary: Mesenchymal cells in POT are positive for vimentin, and subepithelial expression of CD34 and CD138 is often detected, with a low Ki-67 index (< 5%).
Reference Gallery:
Primordial odontogenic tumour. A well-defined unilocular radiolucency surrounding and displacing the second premolar and producing slight root resorption of the first permanent molar.
Primordial odontogenic tumour. Macroscopic appearance. A solid, white mass displacing the enclosed molar towards the periphery, visible just below the surface centrally, and closely associated with two further teeth.
Primordial odontogenic tumour. Macroscopic appearance, with a lobular outline and thin odontogenic epithelial covering.
Primordial odontogenic tumour. The outer layer, with epithelial cells and palisaded cells and a thin fibrous outer capsule.
Primordial odontogenic tumour. Cellular loose mesenchyme.

Q: Microscopically, Primordial Odontogenic Tumor is characterized by a core of loose, cellular mesenchyme that is characteristically surrounded by an outer single layer of [...].
Primordial odontogenic tumour. The outer layer, with epithelial cells and palisaded cells and a thin fibrous outer capsule.
Primordial odontogenic tumour. Cellular loose mesenchyme.
A: columnar or cuboidal epithelium
Back Extra: Primordial Odontogenic Tumour
- Clinical: Primordial odontogenic tumour (POT) usually presents as a well-defined radiolucency associated with unerupted teeth, most commonly the mandibular third molar, and may displace and resorb roots of adjacent teeth.
- Micro: POT is characterized by loose or myxoid fibrous tissue containing variable numbers of fusiform and stellate fibroblasts, surrounded by a single layer of columnar or cuboidal epithelium with scant superficial layers of stellate reticulum-like cells.
- Ancillary: Mesenchymal cells in POT are positive for vimentin, and subepithelial expression of CD34 and CD138 is often detected, with a low Ki-67 index (< 5%).
Reference Gallery:
Primordial odontogenic tumour. A well-defined unilocular radiolucency surrounding and displacing the second premolar and producing slight root resorption of the first permanent molar.
Primordial odontogenic tumour. Macroscopic appearance. A solid, white mass displacing the enclosed molar towards the periphery, visible just below the surface centrally, and closely associated with two further teeth.
Primordial odontogenic tumour. Macroscopic appearance, with a lobular outline and thin odontogenic epithelial covering.
Primordial odontogenic tumour. The outer layer, with epithelial cells and palisaded cells and a thin fibrous outer capsule.
Primordial odontogenic tumour. Cellular loose mesenchyme.

Q: Histologically, an Aneurysmal Bone Cyst is characterized by the presence of [...] that are separated by fibrous septa containing multinucleated osteoclastic giant cells.
Aneurysmal bone cyst. Low-power image showing blood-filled sinusoidal spaces.
Aneurysmal bone cyst. Higher-magnification view of a blood-filled sinusoidal space lined by multinucleated giant cells. The features are relatively nonspecific, but the diagnosis was supported by cytogenetic analysis showing rearrangement of USP6.
A: blood-filled sinusoidal spaces
Back Extra: Aneurysmal Bone Cyst
- Clinical: Aneurysmal bone cysts present as painful jaw enlargements, often causing tooth mobility and displacement. They can lead to root resorption and, in maxillary cases, sinus and orbital involvement.
- Micro: Characterized by blood-filled sinusoidal spaces lined by macrophages and fibroblasts, separated by fibrous septa with multinucleated osteoclastic giant cells. The presence of blue bone is a characteristic but not diagnostic feature.
- Ancillary: Cytogenetic analysis showing a translocation involving USP6 and partners like CDH11 (common in 70% of cases) is highly supportive of the diagnosis, especially in solid-pattern ABCs.
Reference Gallery:
Aneurysmal bone cyst. Low-power image showing blood-filled sinusoidal spaces.
Aneurysmal bone cyst. Higher-magnification view of a blood-filled sinusoidal space lined by multinucleated giant cells. The features are relatively nonspecific, but the diagnosis was supported by cytogenetic analysis showing rearrangement of USP6.
Aneurysmal bone cyst. Solid type, containing clusters of multinucleated giant cells set in a fibroblastic stroma.
Aneurysmal bone cyst. Axial CT showing a circumscribed, partially fluid-filled mass with prominent expansion in the right posterior mandible.
Aneurysmal bone cyst. Panoramic radiograph showing an aneurysmal bone cyst in the posterior body and ramus of the mandible with a typical scalloped outline, cortical erosion, and limited cortication.

Q: Cytogenetic analysis of an Aneurysmal Bone Cyst frequently demonstrates a diagnostic translocation involving the [...] gene (often partnered with CDH11).
Aneurysmal bone cyst. Higher-magnification view of a blood-filled sinusoidal space lined by multinucleated giant cells. The features are relatively nonspecific, but the diagnosis was supported by cytogenetic analysis showing rearrangement of USP6.
A: USP6
Back Extra: Aneurysmal Bone Cyst
- Clinical: Aneurysmal bone cysts present as painful jaw enlargements, often causing tooth mobility and displacement. They can lead to root resorption and, in maxillary cases, sinus and orbital involvement.
- Micro: Characterized by blood-filled sinusoidal spaces lined by macrophages and fibroblasts, separated by fibrous septa with multinucleated osteoclastic giant cells. The presence of blue bone is a characteristic but not diagnostic feature.
- Ancillary: Cytogenetic analysis showing a translocation involving USP6 and partners like CDH11 (common in 70% of cases) is highly supportive of the diagnosis, especially in solid-pattern ABCs.
Reference Gallery:
Aneurysmal bone cyst. Low-power image showing blood-filled sinusoidal spaces.
Aneurysmal bone cyst. Higher-magnification view of a blood-filled sinusoidal space lined by multinucleated giant cells. The features are relatively nonspecific, but the diagnosis was supported by cytogenetic analysis showing rearrangement of USP6.
Aneurysmal bone cyst. Solid type, containing clusters of multinucleated giant cells set in a fibroblastic stroma.
Aneurysmal bone cyst. Axial CT showing a circumscribed, partially fluid-filled mass with prominent expansion in the right posterior mandible.
Aneurysmal bone cyst. Panoramic radiograph showing an aneurysmal bone cyst in the posterior body and ramus of the mandible with a typical scalloped outline, cortical erosion, and limited cortication.

Q: On panoramic radiographs, an Aneurysmal Bone Cyst of the jaw characteristically presents as an expansile mass with cortical erosion and a typical [...] outline.
Aneurysmal bone cyst. Panoramic radiograph showing an aneurysmal bone cyst in the posterior body and ramus of the mandible with a typical scalloped outline, cortical erosion, and limited cortication.
A: scalloped
Back Extra: Aneurysmal Bone Cyst
- Clinical: Aneurysmal bone cysts present as painful jaw enlargements, often causing tooth mobility and displacement. They can lead to root resorption and, in maxillary cases, sinus and orbital involvement.
- Micro: Characterized by blood-filled sinusoidal spaces lined by macrophages and fibroblasts, separated by fibrous septa with multinucleated osteoclastic giant cells. The presence of blue bone is a characteristic but not diagnostic feature.
- Ancillary: Cytogenetic analysis showing a translocation involving USP6 and partners like CDH11 (common in 70% of cases) is highly supportive of the diagnosis, especially in solid-pattern ABCs.
Reference Gallery:
Aneurysmal bone cyst. Low-power image showing blood-filled sinusoidal spaces.
Aneurysmal bone cyst. Higher-magnification view of a blood-filled sinusoidal space lined by multinucleated giant cells. The features are relatively nonspecific, but the diagnosis was supported by cytogenetic analysis showing rearrangement of USP6.
Aneurysmal bone cyst. Solid type, containing clusters of multinucleated giant cells set in a fibroblastic stroma.
Aneurysmal bone cyst. Axial CT showing a circumscribed, partially fluid-filled mass with prominent expansion in the right posterior mandible.
Aneurysmal bone cyst. Panoramic radiograph showing an aneurysmal bone cyst in the posterior body and ramus of the mandible with a typical scalloped outline, cortical erosion, and limited cortication.

Q: A well-delineated unilocular radiolucency that characteristically scallops between the roots of associated vital teeth is a classic presentation of a [...].
Simple bone cyst. Typical presentation of a simple bone cyst affecting the body of the mandible on the left. Note the lesion extending up in a rounded pattern between the roots of the associated teeth.
A: Simple Bone Cyst
Back Extra: Simple Bone Cyst
- Clinical: The vast majority of Simple Bone Cysts are asymptomatic and discovered on routine examination. Radiographically, they are well-delineated unilocular radiolucencies that scallop between the roots of associated vital teeth.
- Micro: Simple Bone Cysts have no epithelial lining and contain thin strips of loosely collagenous or myxoid connective tissue with thin, lace-like fragments of immature bone at the periphery.
- Ancillary: More than half of Simple Bone Cysts in the peripheral skeleton have been shown to harbour either FUS::NFATC2 or EWSR1::NFATC2 fusion, but jaw SBCs have not yet been analysed.
Reference Gallery:
Simple bone cyst. Scrapings from the wall of a simple bone cyst featuring bland fibrous tissue and bone fragments.
Simple bone cyst. Scraping from the wall of a simple bone cyst featuring delicate connective tissue and irregular fragments of bone.
Simple bone cyst. Typical presentation of a simple bone cyst affecting the body of the mandible on the left. Note the lesion extending up in a rounded pattern between the roots of the associated teeth.

Q: Because a Simple Bone Cyst is considered a pseudocyst, histologic examination of the lesional wall reveals loose connective tissue and irregular bone fragments but completely lacks an [...].
Simple bone cyst. Scrapings from the wall of a simple bone cyst featuring bland fibrous tissue and bone fragments.
Simple bone cyst. Scraping from the wall of a simple bone cyst featuring delicate connective tissue and irregular fragments of bone.
A: epithelial lining
Back Extra: Simple Bone Cyst
- Clinical: The vast majority of Simple Bone Cysts are asymptomatic and discovered on routine examination. Radiographically, they are well-delineated unilocular radiolucencies that scallop between the roots of associated vital teeth.
- Micro: Simple Bone Cysts have no epithelial lining and contain thin strips of loosely collagenous or myxoid connective tissue with thin, lace-like fragments of immature bone at the periphery.
- Ancillary: More than half of Simple Bone Cysts in the peripheral skeleton have been shown to harbour either FUS::NFATC2 or EWSR1::NFATC2 fusion, but jaw SBCs have not yet been analysed.
Reference Gallery:
Simple bone cyst. Scrapings from the wall of a simple bone cyst featuring bland fibrous tissue and bone fragments.
Simple bone cyst. Scraping from the wall of a simple bone cyst featuring delicate connective tissue and irregular fragments of bone.
Simple bone cyst. Typical presentation of a simple bone cyst affecting the body of the mandible on the left. Note the lesion extending up in a rounded pattern between the roots of the associated teeth.

Q: Radiographically, Cemento-osseous dysplasia typically presents as asymptomatic, mixed radiopaque and radiolucent lesions that are characteristically associated with the [...].
Cemento-osseous dysplasia. Periapical form, with discrete mixed radiopaque and radiolucent lesions involving the anterior tooth root apices.
Cemento-osseous dysplasia. Focal subtype, similar to the periapical form, but solitary and surrounded by a well-defined osteolytic rim.
A: roots of vital teeth
Back Extra: Cemento-osseous dysplasia
- Clinical: Cemento-osseous dysplasia (COD) is usually asymptomatic and non-expansile, associated with the roots of vital teeth. Some cases may expand, especially in the florid subtype.
- Micro: All COD subtypes exhibit varying proportions of osteoid and woven bone, cementum-like mineralizations, and a cellular fibrous connective tissue stroma.
- Ancillary: Radiological diagnosis is typical, with periodic follow-up for expansion, cyst formation, and osteomyelitis. Surgical intervention is only for symptomatic cases.
Reference Gallery:
Cemento-osseous dysplasia. Irregular woven bone trabeculae and cementum-like particles in a cellular fibrovascular connective tissue background.
Cemento-osseous dysplasia. Periapical form, with discrete mixed radiopaque and radiolucent lesions involving the anterior tooth root apices.
Cemento-osseous dysplasia. Focal subtype, similar to the periapical form, but solitary and surrounded by a well-defined osteolytic rim.
Cemento-osseous dysplasia. Florid subtype. A mixture of radiopaque and radiolucent lesions involving the anterior and posterior mandibular alveolar bone centred on tooth root apices.
Cemento-osseous dysplasia. Woven bone and osteoid in a focally hypercellular stroma.

Q: Histologically, Cemento-osseous dysplasia features a cellular fibrous connective tissue stroma containing irregular woven bone trabeculae and characteristic basophilic [...] mineralizations.
Cemento-osseous dysplasia. Irregular woven bone trabeculae and cementum-like particles in a cellular fibrovascular connective tissue background.
Cemento-osseous dysplasia. Woven bone and osteoid in a focally hypercellular stroma.
A: cementum-like
Back Extra: Cemento-osseous dysplasia
- Clinical: Cemento-osseous dysplasia (COD) is usually asymptomatic and non-expansile, associated with the roots of vital teeth. Some cases may expand, especially in the florid subtype.
- Micro: All COD subtypes exhibit varying proportions of osteoid and woven bone, cementum-like mineralizations, and a cellular fibrous connective tissue stroma.
- Ancillary: Radiological diagnosis is typical, with periodic follow-up for expansion, cyst formation, and osteomyelitis. Surgical intervention is only for symptomatic cases.
Reference Gallery:
Cemento-osseous dysplasia. Irregular woven bone trabeculae and cementum-like particles in a cellular fibrovascular connective tissue background.
Cemento-osseous dysplasia. Periapical form, with discrete mixed radiopaque and radiolucent lesions involving the anterior tooth root apices.
Cemento-osseous dysplasia. Focal subtype, similar to the periapical form, but solitary and surrounded by a well-defined osteolytic rim.
Cemento-osseous dysplasia. Florid subtype. A mixture of radiopaque and radiolucent lesions involving the anterior and posterior mandibular alveolar bone centred on tooth root apices.
Cemento-osseous dysplasia. Woven bone and osteoid in a focally hypercellular stroma.

Q: The [...] subtype of Cemento-osseous dysplasia is distinguished radiographically by widespread, mixed radiopaque and radiolucent lesions that frequently involve multiple jaw quadrants.
Cemento-osseous dysplasia. Florid subtype. A mixture of radiopaque and radiolucent lesions involving the anterior and posterior mandibular alveolar bone centred on tooth root apices.
A: florid
Back Extra: Cemento-osseous dysplasia
- Clinical: Cemento-osseous dysplasia (COD) is usually asymptomatic and non-expansile, associated with the roots of vital teeth. Some cases may expand, especially in the florid subtype.
- Micro: All COD subtypes exhibit varying proportions of osteoid and woven bone, cementum-like mineralizations, and a cellular fibrous connective tissue stroma.
- Ancillary: Radiological diagnosis is typical, with periodic follow-up for expansion, cyst formation, and osteomyelitis. Surgical intervention is only for symptomatic cases.
Reference Gallery:
Cemento-osseous dysplasia. Irregular woven bone trabeculae and cementum-like particles in a cellular fibrovascular connective tissue background.
Cemento-osseous dysplasia. Periapical form, with discrete mixed radiopaque and radiolucent lesions involving the anterior tooth root apices.
Cemento-osseous dysplasia. Focal subtype, similar to the periapical form, but solitary and surrounded by a well-defined osteolytic rim.
Cemento-osseous dysplasia. Florid subtype. A mixture of radiopaque and radiolucent lesions involving the anterior and posterior mandibular alveolar bone centred on tooth root apices.
Cemento-osseous dysplasia. Woven bone and osteoid in a focally hypercellular stroma.

Q: In Familial Gigantiform Cementoma, patients typically present with striking facial deformity due to rapid jaw expansion, while histology reveals a cellular fibroblastic stroma with immature bone and characteristic spheroidal, basophilic [...].
Familial gigantiform cementoma. Cementum-like calcifications appearing as spheroidal to curvilinear deposits of hypocellular, basophilic material.
Familial gigantiform cementoma. A tumour in a 3-year-old girl. A massive expansion of the jaws, causing marked facial deformity.
A: cementum-like calcifications
Back Extra: Familial Gigantiform Cementoma
- Clinical: Rapidly progressive, painless expansion resulting in significant deformity, orbital distortion, and possible airway compromise.
- Micro: Immature bony trabeculae and cementum-like calcifications are seen within a hypercellular fibroblastic stroma.
- Ancillary: None
Reference Gallery:
Familial gigantiform cementoma. CT showing markedly expansile masses with well-circumscribed borders and mixed density in the mandible and maxilla bilaterally.
Familial gigantiform cementoma. Mineralized osteoid and immature bone within a background of cellular fibrous connective tissue.
Familial gigantiform cementoma. Cementum-like calcifications appearing as spheroidal to curvilinear deposits of hypocellular, basophilic material.
Familial gigantiform cementoma. A tumour in a 3-year-old girl. A massive expansion of the jaws, causing marked facial deformity.

Q: Histologically, the woven bone in Fibrous Dysplasia forms irregular, curvilinear trabeculae within a fibrous stroma, classically described as having a [...] appearance.
Fibrous dysplasia. Late-stage disease showing lamellar maturation but retaining irregularly shaped trabeculae and often lacking osteoblastic rimming.
Fibrous dysplasia. Early-stage or active area of the disease with a hypercellular fibrous tissue and condensing woven bone trabeculae, with a focus of giant cells.
Fibrous dysplasia. Maturing area of the lesion with a less cellular stroma and woven bone. Note the osteoblast rimming, which is common in maturing fibrous dysplasia of the jaws, unlike fibrous dysplasia of long bones.
A: "Chinese character"
Back Extra: Fibrous Dysplasia
- Clinical: Fibrous dysplasia presents with painless swelling, orofacial asymmetry, and may cause nasal obstruction, chronic sinusitis, and cranial nerve compression.
- Micro: The lesion consists of woven bone with irregular curvilinear trabeculae and a fibrous stroma, often described as having a 'Chinese character' appearance.
- Ancillary: Confirmation of fibrous dysplasia involves detecting somatic GNAS mutations using next-generation or Sanger sequencing.
Reference Gallery:
Fibrous dysplasia. Late-stage disease showing lamellar maturation but retaining irregularly shaped trabeculae and often lacking osteoblastic rimming.
Fibrous dysplasia. Radiograph of an area affected by fibrous dysplasia. Note the ground-glass appearance, and the loss of lamina dura and cortex definition without tooth displacement.
Fibrous dysplasia. CT, axial view, shows an even, mixed-radiolucency lesion of fibrous dysplasia, with marked expansion of the maxilla but no tooth displacement.
Fibrous dysplasia. Early-stage or active area of the disease with a hypercellular fibrous tissue and condensing woven bone trabeculae, with a focus of giant cells.
Fibrous dysplasia. Maturing area of the lesion with a less cellular stroma and woven bone. Note the osteoblast rimming, which is common in maturing fibrous dysplasia of the jaws, unlike fibrous dysplasia of long bones.

Q: Radiographically, the expansile bone lesions of Fibrous Dysplasia classically demonstrate a diffuse, hazy [...] appearance, often with blending margins and loss of the lamina dura.
Fibrous dysplasia. Radiograph of an area affected by fibrous dysplasia. Note the ground-glass appearance, and the loss of lamina dura and cortex definition without tooth displacement.
Fibrous dysplasia. CT, axial view, shows an even, mixed-radiolucency lesion of fibrous dysplasia, with marked expansion of the maxilla but no tooth displacement.
A: ground-glass
Back Extra: Fibrous Dysplasia
- Clinical: Fibrous dysplasia presents with painless swelling, orofacial asymmetry, and may cause nasal obstruction, chronic sinusitis, and cranial nerve compression.
- Micro: The lesion consists of woven bone with irregular curvilinear trabeculae and a fibrous stroma, often described as having a 'Chinese character' appearance.
- Ancillary: Confirmation of fibrous dysplasia involves detecting somatic GNAS mutations using next-generation or Sanger sequencing.
Reference Gallery:
Fibrous dysplasia. Late-stage disease showing lamellar maturation but retaining irregularly shaped trabeculae and often lacking osteoblastic rimming.
Fibrous dysplasia. Radiograph of an area affected by fibrous dysplasia. Note the ground-glass appearance, and the loss of lamina dura and cortex definition without tooth displacement.
Fibrous dysplasia. CT, axial view, shows an even, mixed-radiolucency lesion of fibrous dysplasia, with marked expansion of the maxilla but no tooth displacement.
Fibrous dysplasia. Early-stage or active area of the disease with a hypercellular fibrous tissue and condensing woven bone trabeculae, with a focus of giant cells.
Fibrous dysplasia. Maturing area of the lesion with a less cellular stroma and woven bone. Note the osteoblast rimming, which is common in maturing fibrous dysplasia of the jaws, unlike fibrous dysplasia of long bones.

Q: Histologically, Juvenile Trabecular Ossifying Fibroma features elongate strands of osteoid often described as '[...]', which are densely rimmed by osteoblasts within a cellular fibroblastic stroma.
Juvenile trabecular ossifying fibroma. A more fibrous area of cellular plump fibroblasts with thin trabeculae of woven bone.
Juvenile trabecular ossifying fibroma. Anastomosing trabeculae of woven bone containing plump osteocytes and lying in a very cellular fibroblastic stroma.
A: brush strokes
Back Extra: Juvenile Trabecular Ossifying Fibroma
- Clinical: Patients typically present with painless jaw expansion, rapid growth, and tooth displacement. Maxillary lesions may cause nasal obstruction and epistaxis.
- Micro: Histopathology reveals an unencapsulated tumor with elongate strands (‘brush strokes’), trabeculae, and sheets of osteoid densely rimmed by osteoblasts in a fibroblastic stroma.
- Ancillary: MDM2 and RASAL1 amplification have been detected in some cases, but diagnostic molecular pathology is not typically relevant.
Reference Gallery:
Juvenile trabecular ossifying fibroma. In actively growing lesions, disorganized sheets of osteoid may raise concern for osteosarcoma.
Juvenile trabecular ossifying fibroma. A more fibrous area of cellular plump fibroblasts with thin trabeculae of woven bone.
Juvenile trabecular ossifying fibroma. Anastomosing trabeculae of woven bone containing plump osteocytes and lying in a very cellular fibroblastic stroma.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Coronal reformatted CT image showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Axial reformatted CT image showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Panoramic radiograph showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.

Q: Radiographically, Juvenile Trabecular Ossifying Fibroma typically presents in children as an expansile jaw lesion with a well-defined [...] margin, internal mineralization, and potential tooth displacement.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Coronal reformatted CT image showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Axial reformatted CT image showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Panoramic radiograph showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.
A: scalloped
Back Extra: Juvenile Trabecular Ossifying Fibroma
- Clinical: Patients typically present with painless jaw expansion, rapid growth, and tooth displacement. Maxillary lesions may cause nasal obstruction and epistaxis.
- Micro: Histopathology reveals an unencapsulated tumor with elongate strands (‘brush strokes’), trabeculae, and sheets of osteoid densely rimmed by osteoblasts in a fibroblastic stroma.
- Ancillary: MDM2 and RASAL1 amplification have been detected in some cases, but diagnostic molecular pathology is not typically relevant.
Reference Gallery:
Juvenile trabecular ossifying fibroma. In actively growing lesions, disorganized sheets of osteoid may raise concern for osteosarcoma.
Juvenile trabecular ossifying fibroma. A more fibrous area of cellular plump fibroblasts with thin trabeculae of woven bone.
Juvenile trabecular ossifying fibroma. Anastomosing trabeculae of woven bone containing plump osteocytes and lying in a very cellular fibroblastic stroma.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Coronal reformatted CT image showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Axial reformatted CT image showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Panoramic radiograph showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.

Q: In actively growing lesions of Juvenile Trabecular Ossifying Fibroma, the presence of disorganized sheets of osteoid may raise concern for a malignant mimic, specifically [...].
Juvenile trabecular ossifying fibroma. In actively growing lesions, disorganized sheets of osteoid may raise concern for osteosarcoma.
A: osteosarcoma
Back Extra: Juvenile Trabecular Ossifying Fibroma
- Clinical: Patients typically present with painless jaw expansion, rapid growth, and tooth displacement. Maxillary lesions may cause nasal obstruction and epistaxis.
- Micro: Histopathology reveals an unencapsulated tumor with elongate strands (‘brush strokes’), trabeculae, and sheets of osteoid densely rimmed by osteoblasts in a fibroblastic stroma.
- Ancillary: MDM2 and RASAL1 amplification have been detected in some cases, but diagnostic molecular pathology is not typically relevant.
Reference Gallery:
Juvenile trabecular ossifying fibroma. In actively growing lesions, disorganized sheets of osteoid may raise concern for osteosarcoma.
Juvenile trabecular ossifying fibroma. A more fibrous area of cellular plump fibroblasts with thin trabeculae of woven bone.
Juvenile trabecular ossifying fibroma. Anastomosing trabeculae of woven bone containing plump osteocytes and lying in a very cellular fibroblastic stroma.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Coronal reformatted CT image showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Axial reformatted CT image showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.
Juvenile trabecular ossifying fibroma. A mandibular juvenile trabecular ossifying fibroma in a 12-year-old child. Panoramic radiograph showing a well-defined scalloped margin, focally perforated cortex, and internal mineralization, with no root resorption but early root growth deflection of the second premolar.

Q: Psammomatoid Ossifying Fibroma is histologically characterized by a hypercellular stroma containing numerous closely packed [...] (psammomatoid mineralizations) with wispy eosinophilic collagen fibers at their periphery.
Psammomatoid ossifying fibroma. Numerous closely packed spherical ossicles or psammomatoid mineralizations in a cellular fibrous stroma.
Psammomatoid ossifying fibroma. Spherical ossicles with a wispy eosinophilic collagenous periphery.
A: spherical ossicles
Back Extra: Psammomatoid Ossifying Fibroma
- Clinical: Psammomatoid ossifying fibroma (PsOF) is usually an asymptomatic, rapidly enlarging bony swelling, though it can cause pain, nasal obstruction, epistaxis, proptosis, and visual disturbance depending on its location.
- Micro: The lesion is characterized by multiple spherical ossicles in a hypercellular stroma of bland ovoid and spindle cells, with wispy eosinophilic collagen fibers at the periphery.
- Ancillary: PsOFs often carry SATB2 gene rearrangements, with breakpoints at Xq26 and 2q33, and may also show MDM2 and RASAL1 amplification.
Reference Gallery:
Psammomatoid ossifying fibroma. Typical facial bone lesion showing early maturation with minimal internal mineralization, marked expansion, and cortical thinning.
Psammomatoid ossifying fibroma. Numerous closely packed spherical ossicles or psammomatoid mineralizations in a cellular fibrous stroma.
Psammomatoid ossifying fibroma. Spherical ossicles with a wispy eosinophilic collagenous periphery.

Q: [...] typically presents as a rapidly enlarging facial bone swelling that demonstrates marked expansion and cortical thinning on radiologic imaging.
Psammomatoid ossifying fibroma. Typical facial bone lesion showing early maturation with minimal internal mineralization, marked expansion, and cortical thinning.
A: Psammomatoid Ossifying Fibroma
Back Extra: Psammomatoid Ossifying Fibroma
- Clinical: Psammomatoid ossifying fibroma (PsOF) is usually an asymptomatic, rapidly enlarging bony swelling, though it can cause pain, nasal obstruction, epistaxis, proptosis, and visual disturbance depending on its location.
- Micro: The lesion is characterized by multiple spherical ossicles in a hypercellular stroma of bland ovoid and spindle cells, with wispy eosinophilic collagen fibers at the periphery.
- Ancillary: PsOFs often carry SATB2 gene rearrangements, with breakpoints at Xq26 and 2q33, and may also show MDM2 and RASAL1 amplification.
Reference Gallery:
Psammomatoid ossifying fibroma. Typical facial bone lesion showing early maturation with minimal internal mineralization, marked expansion, and cortical thinning.
Psammomatoid ossifying fibroma. Numerous closely packed spherical ossicles or psammomatoid mineralizations in a cellular fibrous stroma.
Psammomatoid ossifying fibroma. Spherical ossicles with a wispy eosinophilic collagenous periphery.

Q: Patients typically in their first or second decade presenting with painless unilateral maxillary enlargement, retained primary molars with missing permanent premolars, and characteristic radiographic vertical trabeculation should be evaluated for [...].
Segmental odontomaxillary dysplasia. Fibrous and bony enlargement of the maxillary alveolar mucosa (left side of image). Retained primary molar on the same side.
Segmental odontomaxillary dysplasia. Sequential tomograms reveal an absence of premolars, retained primary molars with root resorption of the second molar, and vertical trabeculation in the affected area of the maxilla.
Segmental odontomaxillary dysplasia. Coarse radiopacities affecting the left side of the maxilla extending to the zygomatic bone and floor of the orbit.
A: Segmental Odontomaxillary Dysplasia
Back Extra: Segmental Odontomaxillary Dysplasia
- Clinical: Patients present with painless maxillary buccal and palatal enlargement, usually in the first or second decade of life, with dental abnormalities including retained primary molars and missing permanent teeth.
- Micro: Histologically, the bone appears inert with irregular bone spicules and multiple accentuated reversal lines, indicating a developmental disorder.
- Ancillary: Radiographic features include coarse radiopacities, vertical trabeculation, and reduced sinus volume, helping to differentiate from other conditions.
Reference Gallery:
Segmental odontomaxillary dysplasia. Abnormal woven and lamellar bone architecture with accentuated and multiple reversal and prominent resting lines associated with fibromyxoid tissue. Note the retraction artefact and lack of bone deposition.
Segmental odontomaxillary dysplasia. Fibrous and bony enlargement of the maxillary alveolar mucosa (left side of image). Retained primary molar on the same side.
Segmental odontomaxillary dysplasia. Sequential tomograms reveal an absence of premolars, retained primary molars with root resorption of the second molar, and vertical trabeculation in the affected area of the maxilla.
Segmental odontomaxillary dysplasia. Coarse radiopacities affecting the left side of the maxilla extending to the zygomatic bone and floor of the orbit.

Q: The microscopic examination of Segmental Odontomaxillary Dysplasia classically reveals "inert" irregular bone spicules with multiple accentuated [...] within a fibromyxoid stroma, indicating a developmental disorder.
Segmental odontomaxillary dysplasia. Abnormal woven and lamellar bone architecture with accentuated and multiple reversal and prominent resting lines associated with fibromyxoid tissue. Note the retraction artefact and lack of bone deposition.
A: reversal lines
Back Extra: Segmental Odontomaxillary Dysplasia
- Clinical: Patients present with painless maxillary buccal and palatal enlargement, usually in the first or second decade of life, with dental abnormalities including retained primary molars and missing permanent teeth.
- Micro: Histologically, the bone appears inert with irregular bone spicules and multiple accentuated reversal lines, indicating a developmental disorder.
- Ancillary: Radiographic features include coarse radiopacities, vertical trabeculation, and reduced sinus volume, helping to differentiate from other conditions.
Reference Gallery:
Segmental odontomaxillary dysplasia. Abnormal woven and lamellar bone architecture with accentuated and multiple reversal and prominent resting lines associated with fibromyxoid tissue. Note the retraction artefact and lack of bone deposition.
Segmental odontomaxillary dysplasia. Fibrous and bony enlargement of the maxillary alveolar mucosa (left side of image). Retained primary molar on the same side.
Segmental odontomaxillary dysplasia. Sequential tomograms reveal an absence of premolars, retained primary molars with root resorption of the second molar, and vertical trabeculation in the affected area of the maxilla.
Segmental odontomaxillary dysplasia. Coarse radiopacities affecting the left side of the maxilla extending to the zygomatic bone and floor of the orbit.

Q: Radiographically, Central Giant Cell Granuloma typically presents as an expansile, multilocular radiolucency with a "honeycomb" appearance, most commonly located in the [...].
Central giant cell granuloma. A typical giant cell granuloma in the posterior body and ramus of the mandible, showing a well-delineated but variably corticated, apparently multilocular radiolucency. Faint internal septa of osteoid and thin bone are present posteriorly, producing a honeycomb appearance.
A: mandible
Back Extra: Central Giant Cell Granuloma
- Clinical: Central Giant Cell Granuloma presents as a well-defined, asymptomatic, slow-growing, expansile radiolucency, often in the mandible.
- Micro: Characterized by osteoclast multinucleated giant cells and mononuclear cells in a vascular stroma, with frequent hemosiderin deposition.
- Ancillary: Somatic mutations in KRAS, FGFR1, and TRPV4 are commonly found, driving MAPK pathway activation.
Reference Gallery:
Central giant cell granuloma. Osteoclast-like giant cells and mononuclear cells in a vascular stroma that also contains trabecular bone and osteoid.
Central giant cell granuloma. High-power image showing relatively small multinucleated osteoclast-type giant cells intermixed with mononuclear cells.
Central giant cell granuloma. A typical giant cell granuloma in the posterior body and ramus of the mandible, showing a well-delineated but variably corticated, apparently multilocular radiolucency. Faint internal septa of osteoid and thin bone are present posteriorly, producing a honeycomb appearance.
Central giant cell granuloma. Low-power view showing small osteoclast-like giant cells in a haemorrhagic background and a relatively well demarcated margin to surrounding bone.

Q: The defining histologic feature of Central Giant Cell Granuloma is a proliferation of mononuclear cells interspersed with [...] set within a vascular, often hemorrhagic stroma.
Central giant cell granuloma. Osteoclast-like giant cells and mononuclear cells in a vascular stroma that also contains trabecular bone and osteoid.
Central giant cell granuloma. High-power image showing relatively small multinucleated osteoclast-type giant cells intermixed with mononuclear cells.
Central giant cell granuloma. Low-power view showing small osteoclast-like giant cells in a haemorrhagic background and a relatively well demarcated margin to surrounding bone.
A: osteoclast-like multinucleated giant cells
Back Extra: Central Giant Cell Granuloma
- Clinical: Central Giant Cell Granuloma presents as a well-defined, asymptomatic, slow-growing, expansile radiolucency, often in the mandible.
- Micro: Characterized by osteoclast multinucleated giant cells and mononuclear cells in a vascular stroma, with frequent hemosiderin deposition.
- Ancillary: Somatic mutations in KRAS, FGFR1, and TRPV4 are commonly found, driving MAPK pathway activation.
Reference Gallery:
Central giant cell granuloma. Osteoclast-like giant cells and mononuclear cells in a vascular stroma that also contains trabecular bone and osteoid.
Central giant cell granuloma. High-power image showing relatively small multinucleated osteoclast-type giant cells intermixed with mononuclear cells.
Central giant cell granuloma. A typical giant cell granuloma in the posterior body and ramus of the mandible, showing a well-delineated but variably corticated, apparently multilocular radiolucency. Faint internal septa of osteoid and thin bone are present posteriorly, producing a honeycomb appearance.
Central giant cell granuloma. Low-power view showing small osteoclast-like giant cells in a haemorrhagic background and a relatively well demarcated margin to surrounding bone.

Q: Radiologically, Cherubism characteristically presents with massive, bilateral, symmetrical expansion of the jaws demonstrating a well-defined, multilocular, [...]-like appearance with cortical thinning.
Cherubism. Panoramic radiograph showing bilateral multilocular radiolucencies in the posterior mandible.
Cherubism. CT coronal reformat showing massive bilateral enlargement of both mandibular rami, with cortical thinning and perforation and an internal honeycomb structure of osteoid or woven bone trabeculae.
A: soap bubble
Back Extra: Cherubism
- Clinical: Slow, symmetrical expansion of the jaws in early childhood, often causing orbital displacement and a characteristic cherubic facial appearance.
- Micro: Abnormally large multinucleated osteoclast-like giant cells in a loose or oedematous spindle cell stroma with perivascular deposits.
- Ancillary: Radiologically, affected bones show a symmetrical, well-defined, multilocular, soap bubble–like appearance with thinned cortex.
Reference Gallery:
Cherubism. Panoramic radiograph showing bilateral multilocular radiolucencies in the posterior mandible.
Cherubism. Much of the lesion is oedematous fibrous tissue with sparse giant cells and sometimes prominent vessels.
Cherubism. Vascular fibrous tissue with scattered multinucleated osteoclast-like giant cells, haemorrhage, and haemosiderin deposits.
Cherubism. CT coronal reformat showing massive bilateral enlargement of both mandibular rami, with cortical thinning and perforation and an internal honeycomb structure of osteoid or woven bone trabeculae.

Q: Microscopically, Cherubism features abnormally large, multinucleated [...] scattered within a loose, edematous spindle cell stroma, often accompanied by hemorrhage and hemosiderin deposits.
Cherubism. Much of the lesion is oedematous fibrous tissue with sparse giant cells and sometimes prominent vessels.
Cherubism. Vascular fibrous tissue with scattered multinucleated osteoclast-like giant cells, haemorrhage, and haemosiderin deposits.
A: osteoclast-like giant cells
Back Extra: Cherubism
- Clinical: Slow, symmetrical expansion of the jaws in early childhood, often causing orbital displacement and a characteristic cherubic facial appearance.
- Micro: Abnormally large multinucleated osteoclast-like giant cells in a loose or oedematous spindle cell stroma with perivascular deposits.
- Ancillary: Radiologically, affected bones show a symmetrical, well-defined, multilocular, soap bubble–like appearance with thinned cortex.
Reference Gallery:
Cherubism. Panoramic radiograph showing bilateral multilocular radiolucencies in the posterior mandible.
Cherubism. Much of the lesion is oedematous fibrous tissue with sparse giant cells and sometimes prominent vessels.
Cherubism. Vascular fibrous tissue with scattered multinucleated osteoclast-like giant cells, haemorrhage, and haemosiderin deposits.
Cherubism. CT coronal reformat showing massive bilateral enlargement of both mandibular rami, with cortical thinning and perforation and an internal honeycomb structure of osteoid or woven bone trabeculae.

Q: Clinically, [...] typically presents as a sessile or pedunculated gingival mass with a characteristic red, maroon, or purple color.
Peripheral giant cell granuloma. The lesion forms a red or maroon gingival enlargement in the left maxilla between two teeth.
A: Peripheral Giant Cell Granuloma
Back Extra: Peripheral Giant Cell Granuloma
- Clinical: Peripheral Giant Cell Granuloma (PGCG) presents as a sessile or pedunculated lump with a smooth, ulcerated, or nodular surface, often with a characteristic red, maroon, or purple colour.
- Micro: PGCG resembles central giant cell granuloma, with an unencapsulated proliferation of mononuclear spindle-shaped and polygonal cells with osteoclast multinucleated cells in a vascular loose fibrous tissue.
- Ancillary: About 70% of PGCGs harbour KRAS mutations, mainly in codons 146 and 12, and 10% have FGFR1 p.C381R or FGFR1 p.N330I mutations.
Reference Gallery:
Peripheral giant cell granuloma. The lesion forms a red or maroon gingival enlargement in the left maxilla between two teeth.
Peripheral giant cell granuloma. Mononuclear and osteoclast-type multinucleated giant cells in a vascular stroma containing some haemosiderin, all covered by oral epithelium. The lesion is microscopically identical to a central giant cell granuloma.
Peripheral giant cell granuloma. A complete lesion. A pedunculated polyp containing a cellular lobular mass of giant cells with haemorrhage.

Q: Microscopically, [...] consists of an unencapsulated mucosal proliferation of mononuclear cells and osteoclast-type multinucleated giant cells set in a vascular stroma with hemosiderin and hemorrhage.
Peripheral giant cell granuloma. Mononuclear and osteoclast-type multinucleated giant cells in a vascular stroma containing some haemosiderin, all covered by oral epithelium. The lesion is microscopically identical to a central giant cell granuloma.
Peripheral giant cell granuloma. A complete lesion. A pedunculated polyp containing a cellular lobular mass of giant cells with haemorrhage.
A: Peripheral Giant Cell Granuloma
Back Extra: Peripheral Giant Cell Granuloma
- Clinical: Peripheral Giant Cell Granuloma (PGCG) presents as a sessile or pedunculated lump with a smooth, ulcerated, or nodular surface, often with a characteristic red, maroon, or purple colour.
- Micro: PGCG resembles central giant cell granuloma, with an unencapsulated proliferation of mononuclear spindle-shaped and polygonal cells with osteoclast multinucleated cells in a vascular loose fibrous tissue.
- Ancillary: About 70% of PGCGs harbour KRAS mutations, mainly in codons 146 and 12, and 10% have FGFR1 p.C381R or FGFR1 p.N330I mutations.
Reference Gallery:
Peripheral giant cell granuloma. The lesion forms a red or maroon gingival enlargement in the left maxilla between two teeth.
Peripheral giant cell granuloma. Mononuclear and osteoclast-type multinucleated giant cells in a vascular stroma containing some haemosiderin, all covered by oral epithelium. The lesion is microscopically identical to a central giant cell granuloma.
Peripheral giant cell granuloma. A complete lesion. A pedunculated polyp containing a cellular lobular mass of giant cells with haemorrhage.

Q: A mixed radiolucent/radiopaque jaw lesion lined by stratified epithelium containing ghost cells and a dentinoid product is a classic presentation of a [...].
Calcifying odontogenic cyst. Typical radiographic presentation as a pericoronal mixed radiolucent/radiopaque lesion of the right posterior mandible and ramus.
Calcifying odontogenic cyst. Areas of the cyst wall containing ghost cells and a homogeneous eosinophilic dentinoid product with cell inclusions.
A: Calcifying Odontogenic Cyst
Back Extra: Calcifying Odontogenic Cyst
- Clinical: Most patients are asymptomatic, although intrabony lesions typically cause cortical expansion. About one-third are uniformly radiolucent, and the remainder are mixed radiolucent/radiopaque.
- Micro: Characterized by a unilocular cyst with a stratified epithelial lining, ghost cells (rounded or stacked flattened pale eosinophilic cells), and dentinoid product.
- Ancillary: Mutations in CTNNB1 (β-catenin) are common, implicating the WNT pathway.
Reference Gallery:
Calcifying odontogenic cyst. Typical radiographic presentation as a pericoronal mixed radiolucent/radiopaque lesion of the right posterior mandible and ramus.
Calcifying odontogenic cyst. Cytological detail of ghost cells devoid of nuclei but with maintenance of cell outlines.
Calcifying odontogenic cyst. Areas of the cyst wall containing ghost cells and a homogeneous eosinophilic dentinoid product with cell inclusions.
Calcifying odontogenic cyst. Cystic architecture with prominent basal cells and numerous homogeneous eosinophilic ghost cells.

Q: The epithelial lining of a Calcifying Odontogenic Cyst is characterized by pale, eosinophilic cells that are devoid of nuclei but maintain their cell outlines, which are termed [...].
Calcifying odontogenic cyst. Cytological detail of ghost cells devoid of nuclei but with maintenance of cell outlines.
Calcifying odontogenic cyst. Cystic architecture with prominent basal cells and numerous homogeneous eosinophilic ghost cells.
A: ghost cells
Back Extra: Calcifying Odontogenic Cyst
- Clinical: Most patients are asymptomatic, although intrabony lesions typically cause cortical expansion. About one-third are uniformly radiolucent, and the remainder are mixed radiolucent/radiopaque.
- Micro: Characterized by a unilocular cyst with a stratified epithelial lining, ghost cells (rounded or stacked flattened pale eosinophilic cells), and dentinoid product.
- Ancillary: Mutations in CTNNB1 (β-catenin) are common, implicating the WNT pathway.
Reference Gallery:
Calcifying odontogenic cyst. Typical radiographic presentation as a pericoronal mixed radiolucent/radiopaque lesion of the right posterior mandible and ramus.
Calcifying odontogenic cyst. Cytological detail of ghost cells devoid of nuclei but with maintenance of cell outlines.
Calcifying odontogenic cyst. Areas of the cyst wall containing ghost cells and a homogeneous eosinophilic dentinoid product with cell inclusions.
Calcifying odontogenic cyst. Cystic architecture with prominent basal cells and numerous homogeneous eosinophilic ghost cells.

Q: Radiographically, a Dentigerous Cyst characteristically presents as a [...] radiolucency around an unerupted tooth (most commonly the lower third molar), attaching at the cementoenamel junction.
Dentigerous cyst. Typical pericoronal radiolucency around the lower third molar, with attachment of the cyst lining at the cementoenamel junction. The associated tooth is displaced posteriorly.
A: pericoronal
Back Extra: Dentigerous Cyst
- Clinical: Most dentigerous cysts are asymptomatic and are discovered on routine dental radiographs or when a tooth fails to erupt.
- Micro: The dentigerous cyst has a thin, non-keratinized stratified squamous epithelial lining, often bilaminar, with occasional mucous or sebaceous metaplasia.
- Ancillary: No specific ancillary studies are required for the diagnosis of dentigerous cysts.
Reference Gallery:
Dentigerous cyst. Thin, regular squamous epithelial lining.
Dentigerous cyst. The thick and hyperplastic epithelial lining of an inflamed dentigerous cyst in relationship to the dense acute and chronic inflammation.
Dentigerous cyst. Typical pericoronal radiolucency around the lower third molar, with attachment of the cyst lining at the cementoenamel junction. The associated tooth is displaced posteriorly.

Q: Microscopically, the thin, non-keratinized stratified squamous epithelial lining of an uninflamed Dentigerous Cyst is typically described as [...] (consisting of 2-3 cell layers) and may exhibit occasional mucous or sebaceous metaplasia.
Dentigerous cyst. Thin, regular squamous epithelial lining.
A: bilaminar
Back Extra: Dentigerous Cyst
- Clinical: Most dentigerous cysts are asymptomatic and are discovered on routine dental radiographs or when a tooth fails to erupt.
- Micro: The dentigerous cyst has a thin, non-keratinized stratified squamous epithelial lining, often bilaminar, with occasional mucous or sebaceous metaplasia.
- Ancillary: No specific ancillary studies are required for the diagnosis of dentigerous cysts.
Reference Gallery:
Dentigerous cyst. Thin, regular squamous epithelial lining.
Dentigerous cyst. The thick and hyperplastic epithelial lining of an inflamed dentigerous cyst in relationship to the dense acute and chronic inflammation.
Dentigerous cyst. Typical pericoronal radiolucency around the lower third molar, with attachment of the cyst lining at the cementoenamel junction. The associated tooth is displaced posteriorly.

Q: Clinically, an adult Gingival Cyst typically presents as a single, painless, well-circumscribed nodule on the attached gingivae, often displaying a characteristic [...] appearance.
Gingival cyst of the adult. A small, well-circumscribed, translucent nodule in the left lower attached gingiva, buccal to the first premolar.
A: bluish-gray translucent
Back Extra: Gingival Cyst
- Clinical: Gingival cyst of the adult (GCA) usually forms a single painless, well-circumscribed nodule of the attached gingivae, sometimes with a bluish-grey translucent appearance.
- Micro: GCA is lined by a thin, flat or cuboidal squamous epithelium, 1–3 cells thick, without rete ridges. Plaque-like thickenings that protrude into the lumen or the connective tissue wall and clear cells are usually present.
- Ancillary: Radiographs are not helpful in detecting GCA, despite occasional superficial erosion of the underlying alveolar bone.
Reference Gallery:
Gingival cyst of the adult. A small, well-circumscribed, translucent nodule in the left lower attached gingiva, buccal to the first premolar.
Gingival cyst of the adult. The cyst is lined by non-keratinized epithelium with two plaque-like thickenings that protrude into the lumen.
Gingival cyst of the adult. Gingival mucosa with an underlying cyst cavity with a thin, inconspicuous epithelial lining.

Q: Histologically, a Gingival Cyst is lined by a thin, flat or cuboidal squamous epithelium (1–3 cells thick) that characteristically features focal [...] protruding into the lumen or connective tissue wall.
Gingival cyst of the adult. The cyst is lined by non-keratinized epithelium with two plaque-like thickenings that protrude into the lumen.
Gingival cyst of the adult. Gingival mucosa with an underlying cyst cavity with a thin, inconspicuous epithelial lining.
A: plaque-like thickenings
Back Extra: Gingival Cyst
- Clinical: Gingival cyst of the adult (GCA) usually forms a single painless, well-circumscribed nodule of the attached gingivae, sometimes with a bluish-grey translucent appearance.
- Micro: GCA is lined by a thin, flat or cuboidal squamous epithelium, 1–3 cells thick, without rete ridges. Plaque-like thickenings that protrude into the lumen or the connective tissue wall and clear cells are usually present.
- Ancillary: Radiographs are not helpful in detecting GCA, despite occasional superficial erosion of the underlying alveolar bone.
Reference Gallery:
Gingival cyst of the adult. A small, well-circumscribed, translucent nodule in the left lower attached gingiva, buccal to the first premolar.
Gingival cyst of the adult. The cyst is lined by non-keratinized epithelium with two plaque-like thickenings that protrude into the lumen.
Gingival cyst of the adult. Gingival mucosa with an underlying cyst cavity with a thin, inconspicuous epithelial lining.

Q: Microscopically, the epithelium of a Glandular Odontogenic Cyst characteristically displays whorled thickenings, duct-like microcysts, and superficial columnar cells that frequently possess [...].
Glandular odontogenic cyst. The epithelial lining shows microcysts and duct-like structures. There is a superficial layer of columnar cells, with cilia in places.
Glandular odontogenic cyst. The lining shows whorled epithelial thickenings and papillary projections. Superficial columnar cells can also be seen.
Glandular odontogenic cyst. A thickening in the epithelium containing glands and with a ciliated surface.
A: cilia
Back Extra: Glandular Odontogenic Cyst
- Clinical: Glandular Odontogenic Cyst (GOC) typically presents as a slowly expanding, painless swelling, often radiologically well-defined and multilocular, with possible tooth displacement or root resorption.
- Micro: GOCs are characterized by a multilocular cystic structure lined with epithelium that can show whorled thickenings, microcysts, apocrine metaplasia, and ciliated cells.
- Ancillary: GOC is generally negative for MAML2 gene rearrangements, although some studies have shown rearrangements in histologically similar lesions, raising the possibility of a pre-existing GOC.
Reference Gallery:
Glandular odontogenic cyst. The epithelial lining shows microcysts and duct-like structures. There is a superficial layer of columnar cells, with cilia in places.
Glandular odontogenic cyst. The lining shows whorled epithelial thickenings and papillary projections. Superficial columnar cells can also be seen.
Glandular odontogenic cyst. An extensive multilocular lesion filling the entire body of the mandible and crossing the midline.
Glandular odontogenic cyst. A thickening in the epithelium containing glands and with a ciliated surface.

Q: Radiographically, a Glandular Odontogenic Cyst typically presents as an extensive, well-defined, [...] radiolucency that can significantly expand the mandible and cross the midline.
Glandular odontogenic cyst. An extensive multilocular lesion filling the entire body of the mandible and crossing the midline.
A: multilocular
Back Extra: Glandular Odontogenic Cyst
- Clinical: Glandular Odontogenic Cyst (GOC) typically presents as a slowly expanding, painless swelling, often radiologically well-defined and multilocular, with possible tooth displacement or root resorption.
- Micro: GOCs are characterized by a multilocular cystic structure lined with epithelium that can show whorled thickenings, microcysts, apocrine metaplasia, and ciliated cells.
- Ancillary: GOC is generally negative for MAML2 gene rearrangements, although some studies have shown rearrangements in histologically similar lesions, raising the possibility of a pre-existing GOC.
Reference Gallery:
Glandular odontogenic cyst. The epithelial lining shows microcysts and duct-like structures. There is a superficial layer of columnar cells, with cilia in places.
Glandular odontogenic cyst. The lining shows whorled epithelial thickenings and papillary projections. Superficial columnar cells can also be seen.
Glandular odontogenic cyst. An extensive multilocular lesion filling the entire body of the mandible and crossing the midline.
Glandular odontogenic cyst. A thickening in the epithelium containing glands and with a ciliated surface.

Q: A(n) [...] typically presents on imaging as a well-demarcated, corticated radiolucency overlying the buccal or distobuccal aspect of a mandibular molar, notably with an intact periodontal or follicular space.
Inflammatory collateral cyst. A mandibular buccal bifurcation cyst overlies the buccal aspect of a mandibular second molar tooth. It appears as a well-demarcated, corticated radiolucency. Note that the periodontal space and lamina dura are intact and normal.
Inflammatory collateral cyst. This cyst appears as a well-demarcated and corticated radiolucency at the distobuccal aspect of an impacted third molar tooth. The follicular space surrounding the crown is intact and normal, seen as a narrow radiolucent rim around the crown posteriorly, excluding dentigerous cyst.
A: Inflammatory Collateral Cyst
Back Extra: Inflammatory Collateral Cyst
- Clinical: Paradental cysts (PCs) are often symptomless, but mandibular buccal bifurcation cysts (MBBCs) may present with pain, tenderness, and suppuration. Imaging shows corticated radiolucencies overlying the buccal or distobuccal aspect of the tooth.
- Micro: The epithelial lining of an inflammatory collateral cyst is squamous and non-keratinized, showing signs of secondary inflammation and arcading rete hyperplasia.
- Ancillary: Cysts are typically enucleated, and third molars associated with PCs are often removed. Molars associated with MBBC can be conserved and usually erupt normally.
Reference Gallery:
Inflammatory collateral cyst. A mandibular buccal bifurcation cyst overlies the buccal aspect of a mandibular second molar tooth. It appears as a well-demarcated, corticated radiolucency. Note that the periodontal space and lamina dura are intact and normal.
Inflammatory collateral cyst. This paradental cyst is composed of an inflamed fibrous wall lined by hyperplastic epithelium. The cyst appears as an open pocket.
Inflammatory collateral cyst. The epithelial lining is squamous and non-keratinized and shows secondary inflammatory changes with arcading rete hyperplasia and has no specific features.
Inflammatory collateral cyst. This cyst appears as a well-demarcated and corticated radiolucency at the distobuccal aspect of an impacted third molar tooth. The follicular space surrounding the crown is intact and normal, seen as a narrow radiolucent rim around the crown posteriorly, excluding dentigerous cyst.

Q: The microscopic appearance of an Inflammatory Collateral Cyst typically consists of an inflamed fibrous wall lined by non-keratinized squamous epithelium exhibiting prominent [...].
Inflammatory collateral cyst. This paradental cyst is composed of an inflamed fibrous wall lined by hyperplastic epithelium. The cyst appears as an open pocket.
Inflammatory collateral cyst. The epithelial lining is squamous and non-keratinized and shows secondary inflammatory changes with arcading rete hyperplasia and has no specific features.
A: arcading rete hyperplasia
Back Extra: Inflammatory Collateral Cyst
- Clinical: Paradental cysts (PCs) are often symptomless, but mandibular buccal bifurcation cysts (MBBCs) may present with pain, tenderness, and suppuration. Imaging shows corticated radiolucencies overlying the buccal or distobuccal aspect of the tooth.
- Micro: The epithelial lining of an inflammatory collateral cyst is squamous and non-keratinized, showing signs of secondary inflammation and arcading rete hyperplasia.
- Ancillary: Cysts are typically enucleated, and third molars associated with PCs are often removed. Molars associated with MBBC can be conserved and usually erupt normally.
Reference Gallery:
Inflammatory collateral cyst. A mandibular buccal bifurcation cyst overlies the buccal aspect of a mandibular second molar tooth. It appears as a well-demarcated, corticated radiolucency. Note that the periodontal space and lamina dura are intact and normal.
Inflammatory collateral cyst. This paradental cyst is composed of an inflamed fibrous wall lined by hyperplastic epithelium. The cyst appears as an open pocket.
Inflammatory collateral cyst. The epithelial lining is squamous and non-keratinized and shows secondary inflammatory changes with arcading rete hyperplasia and has no specific features.
Inflammatory collateral cyst. This cyst appears as a well-demarcated and corticated radiolucency at the distobuccal aspect of an impacted third molar tooth. The follicular space surrounding the crown is intact and normal, seen as a narrow radiolucent rim around the crown posteriorly, excluding dentigerous cyst.

Q: In Lateral Periodontal Cyst and Botryoid Odontogenic Cyst, the cyst wall is classically lined by a thin, non-keratinized epithelium featuring focal, whorled, [...] that contain clear cells.
Lateral periodontal cyst. A cyst with uninflamed fibrous wall lined by a thin cuboidal epithelium a few cells thick, with focal, whorled, plaque-like epithelial thickenings containing clear cells.
Lateral periodontal cyst. High-power view showing clear cells in the epithelium.
Botryoid odontogenic cyst. Uninflamed fibrous wall lined by a thin, non-keratinized squamous epithelium, and focal plaque-like epithelial thickening.
A: plaque-like thickenings
Back Extra: Lateral Periodontal Cyst and Botryoid Odontogenic Cyst
- Clinical: Lateral Periodontal Cyst (LPC) and Botryoid Odontogenic Cyst (BOC) are often asymptomatic and discovered incidentally on radiographs.
- Micro: LPC is characterized by a thin, non-keratinized squamous or cuboidal epithelium with focal whorled, plaque-like thickenings containing clear cells.
- Ancillary: Imaging shows LPC as a well-demarcated, corticated unilocular radiolucency, while BOC has a multilocular appearance.
Reference Gallery:
Lateral periodontal cyst. A cyst with uninflamed fibrous wall lined by a thin cuboidal epithelium a few cells thick, with focal, whorled, plaque-like epithelial thickenings containing clear cells.
Lateral periodontal cyst. High-power view showing clear cells in the epithelium.
Botryoid odontogenic cyst. A cyst showing multiple cystic spaces, with the same histology as lateral periodontal cyst.
Botryoid odontogenic cyst. Uninflamed fibrous wall lined by a thin, non-keratinized squamous epithelium, and focal plaque-like epithelial thickening.
Lateral periodontal and botryoid odontogenic cysts. Left: A typical lateral periodontal cyst producing a unilocular radiolucency between the right lower premolar roots. Right: A typical botryoid odontogenic cyst showing a similar but multilocular cyst in the right mandibular canine/premolar region.

Q: Radiographically in Lateral Periodontal Cyst and Botryoid Odontogenic Cyst, the lateral periodontal cyst typically presents as a well-demarcated unilocular radiolucency between tooth roots, while the botryoid variant distinctively appears [...].
Lateral periodontal and botryoid odontogenic cysts. Left: A typical lateral periodontal cyst producing a unilocular radiolucency between the right lower premolar roots. Right: A typical botryoid odontogenic cyst showing a similar but multilocular cyst in the right mandibular canine/premolar region.
A: multilocular
Back Extra: Lateral Periodontal Cyst and Botryoid Odontogenic Cyst
- Clinical: Lateral Periodontal Cyst (LPC) and Botryoid Odontogenic Cyst (BOC) are often asymptomatic and discovered incidentally on radiographs.
- Micro: LPC is characterized by a thin, non-keratinized squamous or cuboidal epithelium with focal whorled, plaque-like thickenings containing clear cells.
- Ancillary: Imaging shows LPC as a well-demarcated, corticated unilocular radiolucency, while BOC has a multilocular appearance.
Reference Gallery:
Lateral periodontal cyst. A cyst with uninflamed fibrous wall lined by a thin cuboidal epithelium a few cells thick, with focal, whorled, plaque-like epithelial thickenings containing clear cells.
Lateral periodontal cyst. High-power view showing clear cells in the epithelium.
Botryoid odontogenic cyst. A cyst showing multiple cystic spaces, with the same histology as lateral periodontal cyst.
Botryoid odontogenic cyst. Uninflamed fibrous wall lined by a thin, non-keratinized squamous epithelium, and focal plaque-like epithelial thickening.
Lateral periodontal and botryoid odontogenic cysts. Left: A typical lateral periodontal cyst producing a unilocular radiolucency between the right lower premolar roots. Right: A typical botryoid odontogenic cyst showing a similar but multilocular cyst in the right mandibular canine/premolar region.

Q: An incidentally discovered odontogenic lesion presenting as a unilocular or multilocular radiolucency with histology showing a thin epithelium and focal, whorled, plaque-like thickenings containing clear cells is diagnostic of [...].
Lateral periodontal cyst. A cyst with uninflamed fibrous wall lined by a thin cuboidal epithelium a few cells thick, with focal, whorled, plaque-like epithelial thickenings containing clear cells.
Botryoid odontogenic cyst. A cyst showing multiple cystic spaces, with the same histology as lateral periodontal cyst.
Lateral periodontal and botryoid odontogenic cysts. Left: A typical lateral periodontal cyst producing a unilocular radiolucency between the right lower premolar roots. Right: A typical botryoid odontogenic cyst showing a similar but multilocular cyst in the right mandibular canine/premolar region.
A: Lateral Periodontal Cyst and Botryoid Odontogenic Cyst
Back Extra: Lateral Periodontal Cyst and Botryoid Odontogenic Cyst
- Clinical: Lateral Periodontal Cyst (LPC) and Botryoid Odontogenic Cyst (BOC) are often asymptomatic and discovered incidentally on radiographs.
- Micro: LPC is characterized by a thin, non-keratinized squamous or cuboidal epithelium with focal whorled, plaque-like thickenings containing clear cells.
- Ancillary: Imaging shows LPC as a well-demarcated, corticated unilocular radiolucency, while BOC has a multilocular appearance.
Reference Gallery:
Lateral periodontal cyst. A cyst with uninflamed fibrous wall lined by a thin cuboidal epithelium a few cells thick, with focal, whorled, plaque-like epithelial thickenings containing clear cells.
Lateral periodontal cyst. High-power view showing clear cells in the epithelium.
Botryoid odontogenic cyst. A cyst showing multiple cystic spaces, with the same histology as lateral periodontal cyst.
Botryoid odontogenic cyst. Uninflamed fibrous wall lined by a thin, non-keratinized squamous epithelium, and focal plaque-like epithelial thickening.
Lateral periodontal and botryoid odontogenic cysts. Left: A typical lateral periodontal cyst producing a unilocular radiolucency between the right lower premolar roots. Right: A typical botryoid odontogenic cyst showing a similar but multilocular cyst in the right mandibular canine/premolar region.

Q: On occlusal radiographs, a Nasopalatine Duct Cyst classically presents as a well-corticated radiolucency located just posterior to the apices of the [...].
Nasopalatine duct cyst. Occlusal radiograph showing typical radiographic appearances of a corticated radiolucency just behind and around the apices of the upper central incisors.
A: maxillary central incisors
Back Extra: Nasopalatine Duct Cyst
- Clinical: Most Nasopalatine Duct Cysts (NDCs) present as sessile swellings posterior to the maxillary incisors or are asymptomatic.
- Micro: About 90% of NDCs are lined by non-keratinized stratified squamous epithelium, with focal cuboidal, columnar, or ciliated areas.
- Ancillary: Smears of aspirated cysts show degenerative cyst fluid with debris and macrophages, some of which contain haemosiderin. Epithelium is absent or scant.
Reference Gallery:
Nasopalatine duct cyst. The cyst wall is lined by respiratory-type epithelium with thick-walled vessels, fat, and nerves.
Nasopalatine duct cyst. Occlusal radiograph showing typical radiographic appearances of a corticated radiolucency just behind and around the apices of the upper central incisors.
Nasopalatine duct cyst. Three areas (Fig. <<#39306>>, Fig. <<#39307>>, and Fig. <<#39308>>) of the wall from the same cyst showing a range of lining epithelium, from bilaminar cuboidal to low squamous and respiratory. Intermediate appearances are often seen.
Nasopalatine duct cyst. Three areas (Fig. <<#39306>>, Fig. <<#39307>>, and Fig. <<#39308>>) of the wall from the same cyst showing a range of lining epithelium, from bilaminar cuboidal to low squamous and respiratory. Intermediate appearances are often seen.
Nasopalatine duct cyst. Three areas (Fig. <<#39306>>, Fig. <<#39307>>, and Fig. <<#39308>>) of the wall from the same cyst showing a range of lining epithelium, from bilaminar cuboidal to low squamous and respiratory. Intermediate appearances are often seen.

Q: Histologically, the epithelial lining of a Nasopalatine Duct Cyst is highly variable and can range from stratified squamous to ciliated pseudostratified columnar ([...]) epithelium, often with large nerves and thick-walled blood vessels present in the connective tissue wall.
Nasopalatine duct cyst. The cyst wall is lined by respiratory-type epithelium with thick-walled vessels, fat, and nerves.
Nasopalatine duct cyst. Three areas (Fig. <<#39306>>, Fig. <<#39307>>, and Fig. <<#39308>>) of the wall from the same cyst showing a range of lining epithelium, from bilaminar cuboidal to low squamous and respiratory. Intermediate appearances are often seen.
Nasopalatine duct cyst. Three areas (Fig. <<#39306>>, Fig. <<#39307>>, and Fig. <<#39308>>) of the wall from the same cyst showing a range of lining epithelium, from bilaminar cuboidal to low squamous and respiratory. Intermediate appearances are often seen.
A: respiratory
Back Extra: Nasopalatine Duct Cyst
- Clinical: Most Nasopalatine Duct Cysts (NDCs) present as sessile swellings posterior to the maxillary incisors or are asymptomatic.
- Micro: About 90% of NDCs are lined by non-keratinized stratified squamous epithelium, with focal cuboidal, columnar, or ciliated areas.
- Ancillary: Smears of aspirated cysts show degenerative cyst fluid with debris and macrophages, some of which contain haemosiderin. Epithelium is absent or scant.
Reference Gallery:
Nasopalatine duct cyst. The cyst wall is lined by respiratory-type epithelium with thick-walled vessels, fat, and nerves.
Nasopalatine duct cyst. Occlusal radiograph showing typical radiographic appearances of a corticated radiolucency just behind and around the apices of the upper central incisors.
Nasopalatine duct cyst. Three areas (Fig. <<#39306>>, Fig. <<#39307>>, and Fig. <<#39308>>) of the wall from the same cyst showing a range of lining epithelium, from bilaminar cuboidal to low squamous and respiratory. Intermediate appearances are often seen.
Nasopalatine duct cyst. Three areas (Fig. <<#39306>>, Fig. <<#39307>>, and Fig. <<#39308>>) of the wall from the same cyst showing a range of lining epithelium, from bilaminar cuboidal to low squamous and respiratory. Intermediate appearances are often seen.
Nasopalatine duct cyst. Three areas (Fig. <<#39306>>, Fig. <<#39307>>, and Fig. <<#39308>>) of the wall from the same cyst showing a range of lining epithelium, from bilaminar cuboidal to low squamous and respiratory. Intermediate appearances are often seen.

Q: Histologically, the Odontogenic Keratocyst is lined by a thin, parakeratinized stratified squamous epithelium with hyperchromatic, palisaded basal cells that frequently demonstrate [...].
Odontogenic keratocyst. The epithelial cyst lining displays surface parakeratosis, cuboidal to columnar basal cells with hyperchromatic nuclei, and focal reverse nuclear polarity.
Odontogenic keratocyst. Cyst wall lined by uniform stratified squamous–type epithelium without rete ridges but with hyperchromatic palisaded basal cell nuclei and characteristic corrugated surface parakeratin.
A: reverse nuclear polarity
Back Extra: Odontogenic Keratocyst
- Clinical: Odontogenic keratocysts are often asymptomatic, but can present with swelling and bony destruction. They are associated with a high risk of recurrence (20–30%) after enucleation.
- Micro: Histologically, the cyst lining is characterized by a thin, parakeratinized stratified squamous epithelium with hyperchromatic, palisaded basal cells and occasional reverse nuclear polarity.
- Ancillary: Molecular analysis for PTCH1 mutations can help in differentiating ambiguous cystic lesions or possible malignant neoplasms that may mimic odontogenic keratocysts.
Reference Gallery:
Odontogenic keratocyst. Some odontogenic keratocysts display basal budding.
Odontogenic keratocyst. Panoramic radiograph of a large, multilocular odontogenic keratocyst enlarging into the body and ramus of the mandible. The inferior dental nerve canal is displaced inferiorly, but despite the longitudinal extent there is minimal expansion and displacement of teeth.
Odontogenic keratocyst. Microcysts or satellite cysts in the wall.
Odontogenic keratocyst. In areas of inflammation, metaplastic change obscures the characteristic diagnostic features of odontogenic keratocyst epithelium, often preventing diagnosis in inflamed areas or small samples.
Odontogenic keratocyst. The epithelial cyst lining displays surface parakeratosis, cuboidal to columnar basal cells with hyperchromatic nuclei, and focal reverse nuclear polarity.
Odontogenic keratocyst. Cyst wall lined by uniform stratified squamous–type epithelium without rete ridges but with hyperchromatic palisaded basal cell nuclei and characteristic corrugated surface parakeratin.

Q: Radiographically presenting as a uni- or multilocular radiolucency, the Odontogenic Keratocyst is clinically notable for its high rate of [...] (20–30%) following enucleation.
Odontogenic keratocyst. Panoramic radiograph of a large, multilocular odontogenic keratocyst enlarging into the body and ramus of the mandible. The inferior dental nerve canal is displaced inferiorly, but despite the longitudinal extent there is minimal expansion and displacement of teeth.
A: recurrence
Back Extra: Odontogenic Keratocyst
- Clinical: Odontogenic keratocysts are often asymptomatic, but can present with swelling and bony destruction. They are associated with a high risk of recurrence (20–30%) after enucleation.
- Micro: Histologically, the cyst lining is characterized by a thin, parakeratinized stratified squamous epithelium with hyperchromatic, palisaded basal cells and occasional reverse nuclear polarity.
- Ancillary: Molecular analysis for PTCH1 mutations can help in differentiating ambiguous cystic lesions or possible malignant neoplasms that may mimic odontogenic keratocysts.
Reference Gallery:
Odontogenic keratocyst. Some odontogenic keratocysts display basal budding.
Odontogenic keratocyst. Panoramic radiograph of a large, multilocular odontogenic keratocyst enlarging into the body and ramus of the mandible. The inferior dental nerve canal is displaced inferiorly, but despite the longitudinal extent there is minimal expansion and displacement of teeth.
Odontogenic keratocyst. Microcysts or satellite cysts in the wall.
Odontogenic keratocyst. In areas of inflammation, metaplastic change obscures the characteristic diagnostic features of odontogenic keratocyst epithelium, often preventing diagnosis in inflamed areas or small samples.
Odontogenic keratocyst. The epithelial cyst lining displays surface parakeratosis, cuboidal to columnar basal cells with hyperchromatic nuclei, and focal reverse nuclear polarity.
Odontogenic keratocyst. Cyst wall lined by uniform stratified squamous–type epithelium without rete ridges but with hyperchromatic palisaded basal cell nuclei and characteristic corrugated surface parakeratin.

Q: In addition to the classic epithelial lining, the fibrous wall of an Odontogenic Keratocyst may contain small, secondary cavities known as [...] (or microcysts), as well as focal basal budding.
Odontogenic keratocyst. Some odontogenic keratocysts display basal budding.
Odontogenic keratocyst. Microcysts or satellite cysts in the wall.
A: satellite cysts
Back Extra: Odontogenic Keratocyst
- Clinical: Odontogenic keratocysts are often asymptomatic, but can present with swelling and bony destruction. They are associated with a high risk of recurrence (20–30%) after enucleation.
- Micro: Histologically, the cyst lining is characterized by a thin, parakeratinized stratified squamous epithelium with hyperchromatic, palisaded basal cells and occasional reverse nuclear polarity.
- Ancillary: Molecular analysis for PTCH1 mutations can help in differentiating ambiguous cystic lesions or possible malignant neoplasms that may mimic odontogenic keratocysts.
Reference Gallery:
Odontogenic keratocyst. Some odontogenic keratocysts display basal budding.
Odontogenic keratocyst. Panoramic radiograph of a large, multilocular odontogenic keratocyst enlarging into the body and ramus of the mandible. The inferior dental nerve canal is displaced inferiorly, but despite the longitudinal extent there is minimal expansion and displacement of teeth.
Odontogenic keratocyst. Microcysts or satellite cysts in the wall.
Odontogenic keratocyst. In areas of inflammation, metaplastic change obscures the characteristic diagnostic features of odontogenic keratocyst epithelium, often preventing diagnosis in inflamed areas or small samples.
Odontogenic keratocyst. The epithelial cyst lining displays surface parakeratosis, cuboidal to columnar basal cells with hyperchromatic nuclei, and focal reverse nuclear polarity.
Odontogenic keratocyst. Cyst wall lined by uniform stratified squamous–type epithelium without rete ridges but with hyperchromatic palisaded basal cell nuclei and characteristic corrugated surface parakeratin.

Q: Microscopically, an Orthokeratinized Odontogenic Cyst is lined by a thin, regular layer of [...] stratified squamous epithelium with lamellated keratin extending into the lumen.
Orthokeratinized odontogenic cyst. A thin, regular lining of orthokeratinized stratified squamous epithelium. The keratin is lamellated and extends into the lumen.
A: orthokeratinized
Back Extra: Orthokeratinized Odontogenic Cyst
- Clinical: Orthokeratinized Odontogenic Cyst (OOC) typically presents as a painless swelling or is found incidentally on radiographic examination.
- Micro: OOC is characterized by a thin, regular lining of orthokeratinized stratified squamous epithelium with a prominent granular cell layer and heavy keratinization.
- Ancillary: Cytology of an OOC aspirate may show lamellae and fragments of orthokeratin.
Reference Gallery:
Orthokeratinized odontogenic cyst. A thin, regular lining of orthokeratinized stratified squamous epithelium. The keratin is lamellated and extends into the lumen.
Orthokeratinized odontogenic cyst. Radiology shows a well-demarcated and corticated unilocular radiolucency.

Q: On radiographic examination, an Orthokeratinized Odontogenic Cyst typically presents as a well-demarcated and corticated [...].
Orthokeratinized odontogenic cyst. Radiology shows a well-demarcated and corticated unilocular radiolucency.
A: unilocular radiolucency
Back Extra: Orthokeratinized Odontogenic Cyst
- Clinical: Orthokeratinized Odontogenic Cyst (OOC) typically presents as a painless swelling or is found incidentally on radiographic examination.
- Micro: OOC is characterized by a thin, regular lining of orthokeratinized stratified squamous epithelium with a prominent granular cell layer and heavy keratinization.
- Ancillary: Cytology of an OOC aspirate may show lamellae and fragments of orthokeratin.
Reference Gallery:
Orthokeratinized odontogenic cyst. A thin, regular lining of orthokeratinized stratified squamous epithelium. The keratin is lamellated and extends into the lumen.
Orthokeratinized odontogenic cyst. Radiology shows a well-demarcated and corticated unilocular radiolucency.

Q: On imaging, a Radicular Cyst classically presents as a well-demarcated, [...] at the apex of an involved tooth.
Radicular cyst. Periapical radiograph showing a well-demarcated, corticated radiolucency at the apex of an upper incisor tooth.
Radicular cyst. Panoramic radiograph showing a residual radicular cyst at a site of a previous tooth extraction. It appears as a corticated radiolucency.
A: corticated radiolucency
Back Extra: Radicular Cyst
- Clinical: Radicular cysts are often symptomless and found incidentally on radiological investigation, typically as a well-demarcated, corticated radiolucency.
- Micro: The cyst is lined by non-keratinized stratified squamous epithelium with a characteristic arcading pattern and may contain cholesterol clefts and foamy histiocytes.
- Ancillary: Cytology of aspirated cysts may show degenerative cyst fluid with cholesterol crystals and debris.
Reference Gallery:
Radicular cyst. Periapical radiograph showing a well-demarcated, corticated radiolucency at the apex of an upper incisor tooth.
Radicular cyst. Panoramic radiograph showing a residual radicular cyst at a site of a previous tooth extraction. It appears as a corticated radiolucency.
Radicular cyst. The cyst is lined by hyperplastic epithelium showing a characteristic arcading pattern.
Radicular cyst. A cluster of hyaline (Rushton) bodies forms a small nodule in the epithelial lining, indicating an odontogenic cyst.
Radicular cyst. Cholesterol clefts disrupt the epithelial lining and protrude into the cyst lumen.

Q: Microscopically, the non-keratinized stratified squamous epithelium lining a Radicular Cyst typically displays a characteristic [...] pattern.
Radicular cyst. The cyst is lined by hyperplastic epithelium showing a characteristic arcading pattern.
A: arcading
Back Extra: Radicular Cyst
- Clinical: Radicular cysts are often symptomless and found incidentally on radiological investigation, typically as a well-demarcated, corticated radiolucency.
- Micro: The cyst is lined by non-keratinized stratified squamous epithelium with a characteristic arcading pattern and may contain cholesterol clefts and foamy histiocytes.
- Ancillary: Cytology of aspirated cysts may show degenerative cyst fluid with cholesterol crystals and debris.
Reference Gallery:
Radicular cyst. Periapical radiograph showing a well-demarcated, corticated radiolucency at the apex of an upper incisor tooth.
Radicular cyst. Panoramic radiograph showing a residual radicular cyst at a site of a previous tooth extraction. It appears as a corticated radiolucency.
Radicular cyst. The cyst is lined by hyperplastic epithelium showing a characteristic arcading pattern.
Radicular cyst. A cluster of hyaline (Rushton) bodies forms a small nodule in the epithelial lining, indicating an odontogenic cyst.
Radicular cyst. Cholesterol clefts disrupt the epithelial lining and protrude into the cyst lumen.

Q: The epithelial lining of a Radicular Cyst is frequently disrupted by linear, needle-like spaces known as [...], which may protrude into the cyst lumen.
Radicular cyst. Cholesterol clefts disrupt the epithelial lining and protrude into the cyst lumen.
A: cholesterol clefts
Back Extra: Radicular Cyst
- Clinical: Radicular cysts are often symptomless and found incidentally on radiological investigation, typically as a well-demarcated, corticated radiolucency.
- Micro: The cyst is lined by non-keratinized stratified squamous epithelium with a characteristic arcading pattern and may contain cholesterol clefts and foamy histiocytes.
- Ancillary: Cytology of aspirated cysts may show degenerative cyst fluid with cholesterol crystals and debris.
Reference Gallery:
Radicular cyst. Periapical radiograph showing a well-demarcated, corticated radiolucency at the apex of an upper incisor tooth.
Radicular cyst. Panoramic radiograph showing a residual radicular cyst at a site of a previous tooth extraction. It appears as a corticated radiolucency.
Radicular cyst. The cyst is lined by hyperplastic epithelium showing a characteristic arcading pattern.
Radicular cyst. A cluster of hyaline (Rushton) bodies forms a small nodule in the epithelial lining, indicating an odontogenic cyst.
Radicular cyst. Cholesterol clefts disrupt the epithelial lining and protrude into the cyst lumen.

Q: A [...] typically presents radiographically as a well-demarcated unilocular radiolucency and is microscopically lined by pseudostratified ciliated columnar (respiratory-type) epithelium.
Surgical ciliated cyst. Cyst lined by bilaminar cuboidal epithelium with focal cilia.
Surgical ciliated cyst. Cyst lined by fully differentiated respiratory epithelium.
Surgical ciliated cyst. Sagittal CT of a surgical ciliated cyst of the maxilla, from a patient with a history of traumatic tooth extraction.
A: Surgical Ciliated Cyst
Back Extra: Surgical Ciliated Cyst
- Clinical: Surgical ciliated cysts are often asymptomatic but can present with swelling, pain, or tenderness. They appear as a well-demarcated unilocular radiolucency on radiographs.
- Micro: The cyst is lined by pseudostratified ciliated columnar (respiratory-type) epithelium. Mucous (goblet) cells and areas of squamous metaplasia or simple cuboidal cells may be present.
- Ancillary: Treatment involves simple enucleation, and recurrences are rare.
Reference Gallery:
Surgical ciliated cyst. Cyst lined by bilaminar cuboidal epithelium with focal cilia.
Surgical ciliated cyst. Cyst lined by fully differentiated respiratory epithelium.
Surgical ciliated cyst. Sagittal CT of a surgical ciliated cyst of the maxilla, from a patient with a history of traumatic tooth extraction.

Q: Microscopically, the luminal surface of a Surgical Ciliated Cyst is classically lined by [...] (respiratory-type) epithelium, which may also contain mucous (goblet) cells or squamous metaplasia.
Surgical ciliated cyst. Cyst lined by bilaminar cuboidal epithelium with focal cilia.
Surgical ciliated cyst. Cyst lined by fully differentiated respiratory epithelium.
A: pseudostratified ciliated columnar
Back Extra: Surgical Ciliated Cyst
- Clinical: Surgical ciliated cysts are often asymptomatic but can present with swelling, pain, or tenderness. They appear as a well-demarcated unilocular radiolucency on radiographs.
- Micro: The cyst is lined by pseudostratified ciliated columnar (respiratory-type) epithelium. Mucous (goblet) cells and areas of squamous metaplasia or simple cuboidal cells may be present.
- Ancillary: Treatment involves simple enucleation, and recurrences are rare.
Reference Gallery:
Surgical ciliated cyst. Cyst lined by bilaminar cuboidal epithelium with focal cilia.
Surgical ciliated cyst. Cyst lined by fully differentiated respiratory epithelium.
Surgical ciliated cyst. Sagittal CT of a surgical ciliated cyst of the maxilla, from a patient with a history of traumatic tooth extraction.

Q: Histologically, ameloblastic carcinoma demonstrates features of ameloblastomatous differentiation combined with frank malignant characteristics, such as nuclear atypia, increased mitotic figures, and central [...] within the epithelial islands.
Ameloblastic carcinoma. A low-power image demonstrating thick, multilobulated ribbons of tumour in dense fibrous tissue. Extensive necrosis is present in the upper-left corner, with comedonecrosis in the lower-right corner.
Ameloblastic carcinoma. Cellular atypia and apoptotic necrosis in the centre of the follicle.
A: comedonecrosis
Q: Ameloblastic Carcinoma
- Clinical: Patients with [...] often present with jaw or orofacial swelling, pain, and paraesthesia, and may develop tooth mobility and extension into the oral mucosa and trismus.
- Micro: Ameloblastic Carcinoma ([...]) shows variable features of malignancy, including at least moderate cellular or nuclear atypia, increased mitotic activity, and central necrosis in islands.
- Ancillary: [...] mutations are reported in up to 40% of Ameloblastic Carcinoma cases, which can be useful in confirming the diagnosis.
Reference Gallery:
Ameloblastic carcinoma. Composite mandibular segmental resection with temporomandibular joint disarticulation. The mass expands beyond cortical bone, with a large exophytic component.
Ameloblastic carcinoma. A low-power image demonstrating thick, multilobulated ribbons of tumour in dense fibrous tissue. Extensive necrosis is present in the upper-left corner, with comedonecrosis in the lower-right corner.
Ameloblastic carcinoma. Cellular atypia and apoptotic necrosis in the centre of the follicle.
Ameloblastic carcinoma. CT showing a solid mass with heterogeneous enhancement related to tumour necrosis in the left mandible, with marked expansion, cortical destruction, and soft tissue extension.
Ameloblastic carcinoma. Hypercellular area of disorganized and overlapping epithelial cells, exhibiting a high mitotic rate at the periphery of follicles and sheets.
Ameloblastic carcinoma. Spindle cell growth pattern, with stellate reticulum–like cells and less evident peripheral palisading.
Ameloblastic carcinoma. Hypercellular peripheral epithelial compartment with overlapping cells, clear cell change, and necrosis.
A: Ameloblastic Carcinoma; AC; BRAF p.V600E

Q: An aggressive, malignant epithelial odontogenic tumor of the jaw that typically presents with marked cortical destruction, exophytic soft tissue extension, and histologic features of cytologic atypia is diagnosed as [...].
Ameloblastic carcinoma. Composite mandibular segmental resection with temporomandibular joint disarticulation. The mass expands beyond cortical bone, with a large exophytic component.
Ameloblastic carcinoma. CT showing a solid mass with heterogeneous enhancement related to tumour necrosis in the left mandible, with marked expansion, cortical destruction, and soft tissue extension.
A: ameloblastic carcinoma
Q: Ameloblastic Carcinoma
- Clinical: Patients with [...] often present with jaw or orofacial swelling, pain, and paraesthesia, and may develop tooth mobility and extension into the oral mucosa and trismus.
- Micro: Ameloblastic Carcinoma ([...]) shows variable features of malignancy, including at least moderate cellular or nuclear atypia, increased mitotic activity, and central necrosis in islands.
- Ancillary: [...] mutations are reported in up to 40% of Ameloblastic Carcinoma cases, which can be useful in confirming the diagnosis.
Reference Gallery:
Ameloblastic carcinoma. Composite mandibular segmental resection with temporomandibular joint disarticulation. The mass expands beyond cortical bone, with a large exophytic component.
Ameloblastic carcinoma. A low-power image demonstrating thick, multilobulated ribbons of tumour in dense fibrous tissue. Extensive necrosis is present in the upper-left corner, with comedonecrosis in the lower-right corner.
Ameloblastic carcinoma. Cellular atypia and apoptotic necrosis in the centre of the follicle.
Ameloblastic carcinoma. CT showing a solid mass with heterogeneous enhancement related to tumour necrosis in the left mandible, with marked expansion, cortical destruction, and soft tissue extension.
Ameloblastic carcinoma. Hypercellular area of disorganized and overlapping epithelial cells, exhibiting a high mitotic rate at the periphery of follicles and sheets.
Ameloblastic carcinoma. Spindle cell growth pattern, with stellate reticulum–like cells and less evident peripheral palisading.
Ameloblastic carcinoma. Hypercellular peripheral epithelial compartment with overlapping cells, clear cell change, and necrosis.
A: Ameloblastic Carcinoma; AC; BRAF p.V600E

Q: Microscopically, Clear cell odontogenic carcinoma features nests or trabeculae of monomorphic polygonal cells with predominantly [...] cytoplasm set in a prominent hyalinized or fibrocellular stroma.
Clear cell odontogenic carcinoma. The tumour is composed predominantly of optically clear cells.
Clear cell odontogenic carcinoma. Clear cell tumour nests in a prominent fibrocellular stroma.
Clear cell odontogenic carcinoma. The tumour demonstrates cords of cells with clear to faintly eosinophilic cytoplasm in a hyalinized stroma.
A: clear
Back Extra: Clear cell odontogenic carcinoma
- Clinical: Destructive jaw swelling, pain, paraesthesia, tooth mobility, and mucosal ulceration. Metastasis can occur to lymph nodes, lungs, and bone.
- Micro: Lobular sheets, nests, or trabeculae of monomorphic polygonal cells with clear to slightly eosinophilic cytoplasm and eccentric nuclei in a hyalinized or fibrocellular stroma.
- Ancillary: Positive for cytokeratins (AE1/AE3, CK5/6, CK19), p63, and EMA. EWSR1 rearrangements with ATF1 as the most common fusion partner.
Reference Gallery:
Clear cell odontogenic carcinoma. Resection specimen showing a poorly defined, destructive radiolucency in the posterior body and ramus of the mandible.
Clear cell odontogenic carcinoma. The tumour shows a solid biphasic pattern.
Clear cell odontogenic carcinoma. The tumour is composed predominantly of optically clear cells.
Clear cell odontogenic carcinoma. Clear cell tumour nests in a prominent fibrocellular stroma.
Clear cell odontogenic carcinoma. The tumour demonstrates cords of cells with clear to faintly eosinophilic cytoplasm in a hyalinized stroma.

Q: The most common molecular alteration defining Clear cell odontogenic carcinoma is a rearrangement involving the [...] gene (typically fused with ATF1).
Clear cell odontogenic carcinoma. The tumour shows a solid biphasic pattern.
A: EWSR1
Back Extra: Clear cell odontogenic carcinoma
- Clinical: Destructive jaw swelling, pain, paraesthesia, tooth mobility, and mucosal ulceration. Metastasis can occur to lymph nodes, lungs, and bone.
- Micro: Lobular sheets, nests, or trabeculae of monomorphic polygonal cells with clear to slightly eosinophilic cytoplasm and eccentric nuclei in a hyalinized or fibrocellular stroma.
- Ancillary: Positive for cytokeratins (AE1/AE3, CK5/6, CK19), p63, and EMA. EWSR1 rearrangements with ATF1 as the most common fusion partner.
Reference Gallery:
Clear cell odontogenic carcinoma. Resection specimen showing a poorly defined, destructive radiolucency in the posterior body and ramus of the mandible.
Clear cell odontogenic carcinoma. The tumour shows a solid biphasic pattern.
Clear cell odontogenic carcinoma. The tumour is composed predominantly of optically clear cells.
Clear cell odontogenic carcinoma. Clear cell tumour nests in a prominent fibrocellular stroma.
Clear cell odontogenic carcinoma. The tumour demonstrates cords of cells with clear to faintly eosinophilic cytoplasm in a hyalinized stroma.

Q: Clinically and radiographically, Clear cell odontogenic carcinoma frequently presents as a poorly defined, destructive [...] in the jaw (most commonly the mandible).
Clear cell odontogenic carcinoma. Resection specimen showing a poorly defined, destructive radiolucency in the posterior body and ramus of the mandible.
A: radiolucency
Back Extra: Clear cell odontogenic carcinoma
- Clinical: Destructive jaw swelling, pain, paraesthesia, tooth mobility, and mucosal ulceration. Metastasis can occur to lymph nodes, lungs, and bone.
- Micro: Lobular sheets, nests, or trabeculae of monomorphic polygonal cells with clear to slightly eosinophilic cytoplasm and eccentric nuclei in a hyalinized or fibrocellular stroma.
- Ancillary: Positive for cytokeratins (AE1/AE3, CK5/6, CK19), p63, and EMA. EWSR1 rearrangements with ATF1 as the most common fusion partner.
Reference Gallery:
Clear cell odontogenic carcinoma. Resection specimen showing a poorly defined, destructive radiolucency in the posterior body and ramus of the mandible.
Clear cell odontogenic carcinoma. The tumour shows a solid biphasic pattern.
Clear cell odontogenic carcinoma. The tumour is composed predominantly of optically clear cells.
Clear cell odontogenic carcinoma. Clear cell tumour nests in a prominent fibrocellular stroma.
Clear cell odontogenic carcinoma. The tumour demonstrates cords of cells with clear to faintly eosinophilic cytoplasm in a hyalinized stroma.

Q: Ghost Cell Odontogenic Carcinoma features malignant odontogenic epithelium intermixed with aberrant keratinization that appears histologically as [...].
Ghost cell odontogenic carcinoma. Malignant odontogenic epithelium with some peripheral palisading associated with ghost cells and apoptotic necrosis.
Ghost cell odontogenic carcinoma. A solid carcinoma, comprising sheets of malignant hyperchromatic epithelium with scattered clusters of ghost cells. There is no epithelial architecture, peripheral palisading, or evidence of ameloblastic differentiation.
A: ghost cells
Back Extra: Ghost Cell Odontogenic Carcinoma
- Clinical: GCOC may present with nonspecific signs and symptoms such as pain, swelling, ulceration, tooth mobility, and paraesthesia. Imaging typically shows a poorly demarcated radiolucency with internal mineralization.
- Micro: The main component is odontogenic epithelial sheets, islands, and strands, with at least focally reverse polarity, and aberrant keratinization as ghost cells. Evidence of malignancy includes mitotic activity, pleomorphism, hyperchromatism, necrosis, and an infiltrative growth pattern.
- Ancillary: Mutations of CTNNB1 (β-catenin) and APC are reported in GCOC, similar to other tumours with ghost cells and/or dentinoid material. Additional mutations in sonic hedgehog and ATM pathways are also documented.
Reference Gallery:
Ghost cell odontogenic carcinoma. Malignant odontogenic epithelium with some peripheral palisading associated with ghost cells and apoptotic necrosis.
Ghost cell odontogenic carcinoma. A solid carcinoma, comprising sheets of malignant hyperchromatic epithelium with scattered clusters of ghost cells. There is no epithelial architecture, peripheral palisading, or evidence of ameloblastic differentiation.
Ghost cell odontogenic carcinoma. A solid carcinoma, comprising sheets of malignant hyperchromatic epithelium with scattered clusters of ghost cells. There is no epithelial architecture, peripheral palisading, or evidence of ameloblastic differentiation.

Q: [...] is histologically diagnosed when an odontogenic tumor demonstrates sheets of malignant, hyperchromatic epithelium lacking normal architecture, alongside scattered clusters of ghost cells and overt malignant features like necrosis.
Ghost cell odontogenic carcinoma. A solid carcinoma, comprising sheets of malignant hyperchromatic epithelium with scattered clusters of ghost cells. There is no epithelial architecture, peripheral palisading, or evidence of ameloblastic differentiation.
Ghost cell odontogenic carcinoma. A solid carcinoma, comprising sheets of malignant hyperchromatic epithelium with scattered clusters of ghost cells. There is no epithelial architecture, peripheral palisading, or evidence of ameloblastic differentiation.
A: Ghost Cell Odontogenic Carcinoma
Back Extra: Ghost Cell Odontogenic Carcinoma
- Clinical: GCOC may present with nonspecific signs and symptoms such as pain, swelling, ulceration, tooth mobility, and paraesthesia. Imaging typically shows a poorly demarcated radiolucency with internal mineralization.
- Micro: The main component is odontogenic epithelial sheets, islands, and strands, with at least focally reverse polarity, and aberrant keratinization as ghost cells. Evidence of malignancy includes mitotic activity, pleomorphism, hyperchromatism, necrosis, and an infiltrative growth pattern.
- Ancillary: Mutations of CTNNB1 (β-catenin) and APC are reported in GCOC, similar to other tumours with ghost cells and/or dentinoid material. Additional mutations in sonic hedgehog and ATM pathways are also documented.
Reference Gallery:
Ghost cell odontogenic carcinoma. Malignant odontogenic epithelium with some peripheral palisading associated with ghost cells and apoptotic necrosis.
Ghost cell odontogenic carcinoma. A solid carcinoma, comprising sheets of malignant hyperchromatic epithelium with scattered clusters of ghost cells. There is no epithelial architecture, peripheral palisading, or evidence of ameloblastic differentiation.
Ghost cell odontogenic carcinoma. A solid carcinoma, comprising sheets of malignant hyperchromatic epithelium with scattered clusters of ghost cells. There is no epithelial architecture, peripheral palisading, or evidence of ameloblastic differentiation.

Q: A defining histologic feature of Odontogenic Carcinosarcoma is a true biphasic pattern where both the epithelial and ectomesenchymal components exhibit cytological features of [...] (e.g., hypercellularity, pleomorphism, and frequent mitoses), often alongside dentinoid production.
Odontogenic carcinosarcoma. Islands of highly cellular and poorly differentiated epithelium lying in a stromal component producing abundant dentinoid.
Odontogenic carcinosarcoma. The epithelial component shows high cellularity, some pleomorphism and hyperchromatism, and frequent mitoses.
Odontogenic carcinosarcoma. The ectomesenchymal component shows hypercellularity, some pleomorphism, hyperchromatism, increased mitoses, and extensive dentinoid.
A: malignancy
Q: Odontogenic Carcinosarcoma
- Clinical: Most patients with [...] present with pain, swelling, and paraesthesia, with a mean tumour diameter of approximately 60 mm at diagnosis.
- Micro: Histologically, [...] shows both epithelial and ectomesenchymal components with cytological features of malignancy, including high cellularity, pleomorphism, and frequent mitoses.
- Ancillary: The epithelial component of [...] is reactive for cytokeratins, particularly CK19, while the ectomesenchymal component is invariably positive for vimentin.
Reference Gallery:
Odontogenic carcinosarcoma. Islands of highly cellular and poorly differentiated epithelium lying in a stromal component producing abundant dentinoid.
Odontogenic carcinosarcoma. The epithelial component shows high cellularity, some pleomorphism and hyperchromatism, and frequent mitoses.
Odontogenic carcinosarcoma. The ectomesenchymal component shows hypercellularity, some pleomorphism, hyperchromatism, increased mitoses, and extensive dentinoid.
Odontogenic carcinosarcoma. Axial CT shows a large, expansile, radiolucent lesion of the left mandible, with cortical destruction.
A: odontogenic carcinosarcoma; odontogenic carcinosarcoma; odontogenic carcinosarcoma

Q: Radiographically, Odontogenic Carcinosarcoma typically presents as a large, expansile, [...] lesion with aggressive cortical destruction, frequently causing clinical pain, swelling, and paresthesia.
Odontogenic carcinosarcoma. Axial CT shows a large, expansile, radiolucent lesion of the left mandible, with cortical destruction.
A: radiolucent
Q: Odontogenic Carcinosarcoma
- Clinical: Most patients with [...] present with pain, swelling, and paraesthesia, with a mean tumour diameter of approximately 60 mm at diagnosis.
- Micro: Histologically, [...] shows both epithelial and ectomesenchymal components with cytological features of malignancy, including high cellularity, pleomorphism, and frequent mitoses.
- Ancillary: The epithelial component of [...] is reactive for cytokeratins, particularly CK19, while the ectomesenchymal component is invariably positive for vimentin.
Reference Gallery:
Odontogenic carcinosarcoma. Islands of highly cellular and poorly differentiated epithelium lying in a stromal component producing abundant dentinoid.
Odontogenic carcinosarcoma. The epithelial component shows high cellularity, some pleomorphism and hyperchromatism, and frequent mitoses.
Odontogenic carcinosarcoma. The ectomesenchymal component shows hypercellularity, some pleomorphism, hyperchromatism, increased mitoses, and extensive dentinoid.
Odontogenic carcinosarcoma. Axial CT shows a large, expansile, radiolucent lesion of the left mandible, with cortical destruction.
A: odontogenic carcinosarcoma; odontogenic carcinosarcoma; odontogenic carcinosarcoma

Q: In odontogenic sarcoma, the hallmark histologic finding is a biphasic tumor featuring a hypercellular, malignant ectomesenchymal component paired with an epithelial component that is characteristically cytologically [...].
Ameloblastic fibrosarcoma. Mixed odontogenic tumour in which the epithelial component is cytologically bland but the ectomesenchymal component displays hypercellularity.
A: bland
Back Extra: Odontogenic Sarcoma
- Clinical: Patients present with locally aggressive expansile lesions, often with pain and cortical destruction.
- Micro: The ectomesenchymal component is hypercellular with cytological atypia and a high mitotic index, while the epithelial component is cytologically bland.
- Ancillary: BRAF p.V600E activating mutations are commonly found in the mesenchymal component of odontogenic sarcomas.
Reference Gallery:
Odontogenic sarcoma. Radiographic image showing a poorly marginated osteolytic radiolucency of the right posterior mandible.
Ameloblastic fibrosarcoma. Mixed odontogenic tumour in which the epithelial component is cytologically bland but the ectomesenchymal component displays hypercellularity.
Odontogenic sarcoma. At high magnification, the ectomesenchymal component is hypercellular, with cytological atypia and a high mitotic index.

Q: In odontogenic sarcoma, the cytological atypia and high mitotic index are restricted strictly to the [...] component of the tumor.
Odontogenic sarcoma. At high magnification, the ectomesenchymal component is hypercellular, with cytological atypia and a high mitotic index.
A: ectomesenchymal
Back Extra: Odontogenic Sarcoma
- Clinical: Patients present with locally aggressive expansile lesions, often with pain and cortical destruction.
- Micro: The ectomesenchymal component is hypercellular with cytological atypia and a high mitotic index, while the epithelial component is cytologically bland.
- Ancillary: BRAF p.V600E activating mutations are commonly found in the mesenchymal component of odontogenic sarcomas.
Reference Gallery:
Odontogenic sarcoma. Radiographic image showing a poorly marginated osteolytic radiolucency of the right posterior mandible.
Ameloblastic fibrosarcoma. Mixed odontogenic tumour in which the epithelial component is cytologically bland but the ectomesenchymal component displays hypercellularity.
Odontogenic sarcoma. At high magnification, the ectomesenchymal component is hypercellular, with cytological atypia and a high mitotic index.

Q: Radiographic imaging of an odontogenic sarcoma typically reveals a locally aggressive, poorly marginated, [...] radiolucency that frequently causes pain and cortical destruction.
Odontogenic sarcoma. Radiographic image showing a poorly marginated osteolytic radiolucency of the right posterior mandible.
A: osteolytic
Back Extra: Odontogenic Sarcoma
- Clinical: Patients present with locally aggressive expansile lesions, often with pain and cortical destruction.
- Micro: The ectomesenchymal component is hypercellular with cytological atypia and a high mitotic index, while the epithelial component is cytologically bland.
- Ancillary: BRAF p.V600E activating mutations are commonly found in the mesenchymal component of odontogenic sarcomas.
Reference Gallery:
Odontogenic sarcoma. Radiographic image showing a poorly marginated osteolytic radiolucency of the right posterior mandible.
Ameloblastic fibrosarcoma. Mixed odontogenic tumour in which the epithelial component is cytologically bland but the ectomesenchymal component displays hypercellularity.
Odontogenic sarcoma. At high magnification, the ectomesenchymal component is hypercellular, with cytological atypia and a high mitotic index.

Q: Advanced cases of [...] often present radiographically as poorly defined osteolytic areas causing cortical erosion, tooth root resorption, and eventually painful expansion, paresthesia, and pathological fractures.
Primary intraosseous carcinoma NOS. This radiolucency associated with the lower third molar presented in an 82-year-old man and had increased in size when compared with a panoramic radiograph taken 7 years earlier, and it had developed a poorly defined periphery. There was complete bony destruction of buccal cortex, root resorption, and paraesthesia along the distribution of the right inferior alveolar nerve.
Primary intraosseous carcinoma NOS. Two years after the image shown in Fig. 39433, there is extensive poorly localized destruction and pathological fracture.
A: Primary Intraosseous Carcinoma NOS
Back Extra: Primary Intraosseous Carcinoma NOS
- Clinical: Primary Intraosseous Carcinoma NOS often presents with a poorly defined osteolytic area, cortical erosion, and tooth root resorption. Advanced cases may show painful expansion, pathological fractures, and paraesthesia.
- Micro: Primary Intraosseous Carcinoma NOS is characterized by islands and nests of atypical squamous epithelium with minimal keratinization. Most cases are moderately differentiated, with occasional severe cytological atypia.
- Ancillary: CK19 positivity on immunohistochemistry can support an odontogenic origin, but it has low specificity. No specific molecular markers are described.
Reference Gallery:
Primary intraosseous carcinoma NOS. This radiolucency associated with the lower third molar presented in an 82-year-old man and had increased in size when compared with a panoramic radiograph taken 7 years earlier, and it had developed a poorly defined periphery. There was complete bony destruction of buccal cortex, root resorption, and paraesthesia along the distribution of the right inferior alveolar nerve.
Primary intraosseous carcinoma NOS. Typical squamous carcinoma that arose in an odontogenic cyst.
Primary intraosseous carcinoma NOS. This primary intraosseous carcinoma is arising from a pre-existing odontogenic cyst. A search for definite cytological atypia, mitotic activity, and invasion may be required, because hyperplastic islands of epithelium often develop in the walls of odontogenic cysts, and those primary intraosseous carcinomas that arise in cysts are often well differentiated.
Primary intraosseous carcinoma NOS. Subtle early signs of intraosseous carcinoma in the dental follicle of an unerupted lower premolar, with slight expansion and loss of cortication.
Primary intraosseous carcinoma NOS. Two years after the image shown in Fig. 39433, there is extensive poorly localized destruction and pathological fracture.

Q: Histologically, Primary Intraosseous Carcinoma NOS features islands of atypical squamous epithelium with minimal keratinization, and many well-differentiated cases demonstrably arise from the epithelial lining of a pre-existing [...].
Primary intraosseous carcinoma NOS. Typical squamous carcinoma that arose in an odontogenic cyst.
Primary intraosseous carcinoma NOS. This primary intraosseous carcinoma is arising from a pre-existing odontogenic cyst. A search for definite cytological atypia, mitotic activity, and invasion may be required, because hyperplastic islands of epithelium often develop in the walls of odontogenic cysts, and those primary intraosseous carcinomas that arise in cysts are often well differentiated.
A: odontogenic cyst
Back Extra: Primary Intraosseous Carcinoma NOS
- Clinical: Primary Intraosseous Carcinoma NOS often presents with a poorly defined osteolytic area, cortical erosion, and tooth root resorption. Advanced cases may show painful expansion, pathological fractures, and paraesthesia.
- Micro: Primary Intraosseous Carcinoma NOS is characterized by islands and nests of atypical squamous epithelium with minimal keratinization. Most cases are moderately differentiated, with occasional severe cytological atypia.
- Ancillary: CK19 positivity on immunohistochemistry can support an odontogenic origin, but it has low specificity. No specific molecular markers are described.
Reference Gallery:
Primary intraosseous carcinoma NOS. This radiolucency associated with the lower third molar presented in an 82-year-old man and had increased in size when compared with a panoramic radiograph taken 7 years earlier, and it had developed a poorly defined periphery. There was complete bony destruction of buccal cortex, root resorption, and paraesthesia along the distribution of the right inferior alveolar nerve.
Primary intraosseous carcinoma NOS. Typical squamous carcinoma that arose in an odontogenic cyst.
Primary intraosseous carcinoma NOS. This primary intraosseous carcinoma is arising from a pre-existing odontogenic cyst. A search for definite cytological atypia, mitotic activity, and invasion may be required, because hyperplastic islands of epithelium often develop in the walls of odontogenic cysts, and those primary intraosseous carcinomas that arise in cysts are often well differentiated.
Primary intraosseous carcinoma NOS. Subtle early signs of intraosseous carcinoma in the dental follicle of an unerupted lower premolar, with slight expansion and loss of cortication.
Primary intraosseous carcinoma NOS. Two years after the image shown in Fig. 39433, there is extensive poorly localized destruction and pathological fracture.

Q: [...] is an infiltrative tumor characterized histologically by malignant epithelial cells forming thin cords and small nests embedded within a dense, fibrocollagenous sclerotic stroma.
Sclerosing odontogenic carcinoma. A cellular example with less sclerotic stroma showing haphazardly arranged thin cords, strands, and small nests of epithelium blending with loose and dense collagenous stroma. Mild inflammation is present in the background, which can cause some difficulty in distinguishing the epithelial component.
Sclerosing odontogenic carcinoma. Typical appearance, with extensive sclerosis of the stroma and dispersed, sometimes inconspicuous, epithelial islands and strands.
A: Sclerosing Odontogenic Carcinoma
Back Extra: Sclerosing Odontogenic Carcinoma
- Clinical: Sclerosing odontogenic carcinoma (SOC) often presents as a swelling that can grow rapidly, with occasional paraesthesia in mandibular cases. Radiographically, it appears as a poorly defined radiolucency with cortical bone destruction.
- Micro: A dense, fibrocollagenous sclerotic stroma containing malignant epithelial cells forming thin cords, strands, and small nests. Mild cellular atypia and infiltrative growth are common, with perineural invasion frequently observed.
- Ancillary: CK19 immunostain highlights the epithelial component, and all cases tested have been negative for EWSR1 rearrangement.
Reference Gallery:
Sclerosing odontogenic carcinoma. A cellular example with less sclerotic stroma showing haphazardly arranged thin cords, strands, and small nests of epithelium blending with loose and dense collagenous stroma. Mild inflammation is present in the background, which can cause some difficulty in distinguishing the epithelial component.
Sclerosing odontogenic carcinoma. Typical appearance, with extensive sclerosis of the stroma and dispersed, sometimes inconspicuous, epithelial islands and strands.
Sclerosing odontogenic carcinoma. CK19 immunostain highlights the epithelial component.
Sclerosing odontogenic carcinoma. Radiographic image showing a relatively low-grade tumour appearance, with a well-defined and partly corticated outline.

Q: Sclerosing Odontogenic Carcinoma contains dispersed and sometimes inconspicuous epithelial islands and strands that are consistently highlighted by a [...] immunostain.
Sclerosing odontogenic carcinoma. CK19 immunostain highlights the epithelial component.
A: CK19
Back Extra: Sclerosing Odontogenic Carcinoma
- Clinical: Sclerosing odontogenic carcinoma (SOC) often presents as a swelling that can grow rapidly, with occasional paraesthesia in mandibular cases. Radiographically, it appears as a poorly defined radiolucency with cortical bone destruction.
- Micro: A dense, fibrocollagenous sclerotic stroma containing malignant epithelial cells forming thin cords, strands, and small nests. Mild cellular atypia and infiltrative growth are common, with perineural invasion frequently observed.
- Ancillary: CK19 immunostain highlights the epithelial component, and all cases tested have been negative for EWSR1 rearrangement.
Reference Gallery:
Sclerosing odontogenic carcinoma. A cellular example with less sclerotic stroma showing haphazardly arranged thin cords, strands, and small nests of epithelium blending with loose and dense collagenous stroma. Mild inflammation is present in the background, which can cause some difficulty in distinguishing the epithelial component.
Sclerosing odontogenic carcinoma. Typical appearance, with extensive sclerosis of the stroma and dispersed, sometimes inconspicuous, epithelial islands and strands.
Sclerosing odontogenic carcinoma. CK19 immunostain highlights the epithelial component.
Sclerosing odontogenic carcinoma. Radiographic image showing a relatively low-grade tumour appearance, with a well-defined and partly corticated outline.

Q: Although often destructive, [...] may radiographically present with a relatively low-grade tumor appearance, featuring a well-defined and partly corticated outline.
Sclerosing odontogenic carcinoma. Radiographic image showing a relatively low-grade tumour appearance, with a well-defined and partly corticated outline.
A: Sclerosing Odontogenic Carcinoma
Back Extra: Sclerosing Odontogenic Carcinoma
- Clinical: Sclerosing odontogenic carcinoma (SOC) often presents as a swelling that can grow rapidly, with occasional paraesthesia in mandibular cases. Radiographically, it appears as a poorly defined radiolucency with cortical bone destruction.
- Micro: A dense, fibrocollagenous sclerotic stroma containing malignant epithelial cells forming thin cords, strands, and small nests. Mild cellular atypia and infiltrative growth are common, with perineural invasion frequently observed.
- Ancillary: CK19 immunostain highlights the epithelial component, and all cases tested have been negative for EWSR1 rearrangement.
Reference Gallery:
Sclerosing odontogenic carcinoma. A cellular example with less sclerotic stroma showing haphazardly arranged thin cords, strands, and small nests of epithelium blending with loose and dense collagenous stroma. Mild inflammation is present in the background, which can cause some difficulty in distinguishing the epithelial component.
Sclerosing odontogenic carcinoma. Typical appearance, with extensive sclerosis of the stroma and dispersed, sometimes inconspicuous, epithelial islands and strands.
Sclerosing odontogenic carcinoma. CK19 immunostain highlights the epithelial component.
Sclerosing odontogenic carcinoma. Radiographic image showing a relatively low-grade tumour appearance, with a well-defined and partly corticated outline.

Q: On CT imaging, a well-differentiated Chondrosarcoma classically demonstrates characteristic cartilaginous [...].
Chondrosarcoma. Grade 1. A tumour of the nasal septum containing the typical cartilaginous popcorn calcifications. CT, sagittal reconstruction.
A: popcorn calcifications
Back Extra: Chondrosarcoma
- Clinical: Chondrosarcoma can present with nasal obstruction if it involves the nose, or as asymptomatic or painful swelling at other sites.
- Micro: Well-differentiated chondrosarcomas have a lobular morphology with small, uniform nuclei in a basophilic matrix. Higher grades show increased cellularity, nuclear pleomorphism, and mitoses.
- Ancillary: Immunohistochemistry typically shows tumour cells staining for S100, SOX9, ERG, and podoplanin. IDH1/2 mutations can help distinguish conventional chondrosarcoma from chondroblastic osteosarcoma.
Reference Gallery:
Chondrosarcoma. Grade 2. Cartilaginous tumour formation showing permeative and osteodestructive growth.
Chondrosarcoma. Grade 1. A tumour of the nasal septum containing the typical cartilaginous popcorn calcifications. CT, sagittal reconstruction.
Chondrosarcoma. Grade 2. Lobules of neoplastic cartilage infiltrating the submucosal soft tissues.

Q: Microscopically, Chondrosarcoma is characterized by a [...] morphology composed of neoplastic cartilage within a basophilic matrix, often exhibiting permeative and osteodestructive growth into adjacent tissues.
Chondrosarcoma. Grade 2. Cartilaginous tumour formation showing permeative and osteodestructive growth.
Chondrosarcoma. Grade 2. Lobules of neoplastic cartilage infiltrating the submucosal soft tissues.
A: lobular
Back Extra: Chondrosarcoma
- Clinical: Chondrosarcoma can present with nasal obstruction if it involves the nose, or as asymptomatic or painful swelling at other sites.
- Micro: Well-differentiated chondrosarcomas have a lobular morphology with small, uniform nuclei in a basophilic matrix. Higher grades show increased cellularity, nuclear pleomorphism, and mitoses.
- Ancillary: Immunohistochemistry typically shows tumour cells staining for S100, SOX9, ERG, and podoplanin. IDH1/2 mutations can help distinguish conventional chondrosarcoma from chondroblastic osteosarcoma.
Reference Gallery:
Chondrosarcoma. Grade 2. Cartilaginous tumour formation showing permeative and osteodestructive growth.
Chondrosarcoma. Grade 1. A tumour of the nasal septum containing the typical cartilaginous popcorn calcifications. CT, sagittal reconstruction.
Chondrosarcoma. Grade 2. Lobules of neoplastic cartilage infiltrating the submucosal soft tissues.

Q: A biphasic malignant bone tumor consisting of well-differentiated cartilage lobules admixed with small, uniform, round to spindle-shaped cells exhibiting a hemangiopericytoma-like vascular pattern is characteristic of [...].
Mesenchymal chondrosarcoma. The characteristic histological feature is a bimorphic pattern: small, uniform, round to spindle-shaped cells with a perivascular haemangiopericytoma–like pattern and admixed cartilaginous tissue.
Mesenchymal chondrosarcoma. At low magnification, the characteristic histological feature is small, uniform, round to spindle-shaped cells that resemble Ewing sarcoma, with a perivascular haemangiopericytoma–like pattern, necrosis, and mineralization in cartilage islands.
A: Mesenchymal Chondrosarcoma
Q: Mesenchymal Chondrosarcoma
- Clinical: Patients with [...] present with swelling, pain, and possible pathological fracture, often with an aggressive lytic and destructive mass on imaging.
- Micro: Histologically, [...] is characterized by a biphasic pattern of small, uniform, round to spindle-shaped cells and well-differentiated cartilage lobules.
- Ancillary: [...] shows diffuse strong membrane positivity for CD99 and nuclear SOX9 immunoreactivity.
Reference Gallery:
Mesenchymal chondrosarcoma. The characteristic histological feature is a bimorphic pattern: small, uniform, round to spindle-shaped cells with a perivascular haemangiopericytoma–like pattern and admixed cartilaginous tissue.
Mesenchymal chondrosarcoma. At low magnification, the characteristic histological feature is small, uniform, round to spindle-shaped cells that resemble Ewing sarcoma, with a perivascular haemangiopericytoma–like pattern, necrosis, and mineralization in cartilage islands.
Mesenchymal chondrosarcoma. Immunohistochemistry includes diffuse strong membrane positivity for CD99 on the mesenchymal small cell component.
Mesenchymal chondrosarcoma. Nuclear SOX9 immunoreactivity has a patchy distribution in both the small cell and chondroid components.
Mesenchymal chondrosarcoma. An aggressive tumour of the nasal cavity infiltrating the surrounding structures, with cortical destruction and patchy internal mineralization. CT, coronal reconstruction.
A: Mesenchymal Chondrosarcoma; Mesenchymal Chondrosarcoma; Mesenchymal Chondrosarcoma

Q: Immunohistochemically, the small cell component of Mesenchymal Chondrosarcoma classically shows diffuse, strong membrane positivity for [...] (mimicking Ewing sarcoma), while both the small cell and chondroid components show nuclear positivity for SOX9.
Mesenchymal chondrosarcoma. Immunohistochemistry includes diffuse strong membrane positivity for CD99 on the mesenchymal small cell component.
Mesenchymal chondrosarcoma. Nuclear SOX9 immunoreactivity has a patchy distribution in both the small cell and chondroid components.
A: CD99
Q: Mesenchymal Chondrosarcoma
- Clinical: Patients with [...] present with swelling, pain, and possible pathological fracture, often with an aggressive lytic and destructive mass on imaging.
- Micro: Histologically, [...] is characterized by a biphasic pattern of small, uniform, round to spindle-shaped cells and well-differentiated cartilage lobules.
- Ancillary: [...] shows diffuse strong membrane positivity for CD99 and nuclear SOX9 immunoreactivity.
Reference Gallery:
Mesenchymal chondrosarcoma. The characteristic histological feature is a bimorphic pattern: small, uniform, round to spindle-shaped cells with a perivascular haemangiopericytoma–like pattern and admixed cartilaginous tissue.
Mesenchymal chondrosarcoma. At low magnification, the characteristic histological feature is small, uniform, round to spindle-shaped cells that resemble Ewing sarcoma, with a perivascular haemangiopericytoma–like pattern, necrosis, and mineralization in cartilage islands.
Mesenchymal chondrosarcoma. Immunohistochemistry includes diffuse strong membrane positivity for CD99 on the mesenchymal small cell component.
Mesenchymal chondrosarcoma. Nuclear SOX9 immunoreactivity has a patchy distribution in both the small cell and chondroid components.
Mesenchymal chondrosarcoma. An aggressive tumour of the nasal cavity infiltrating the surrounding structures, with cortical destruction and patchy internal mineralization. CT, coronal reconstruction.
A: Mesenchymal Chondrosarcoma; Mesenchymal Chondrosarcoma; Mesenchymal Chondrosarcoma

Q: On imaging (such as CT), Mesenchymal Chondrosarcoma presents as an aggressive, osteolytic and destructive mass often featuring [...] corresponding to its well-differentiated cartilage islands.
Mesenchymal chondrosarcoma. An aggressive tumour of the nasal cavity infiltrating the surrounding structures, with cortical destruction and patchy internal mineralization. CT, coronal reconstruction.
A: patchy internal mineralization
Q: Mesenchymal Chondrosarcoma
- Clinical: Patients with [...] present with swelling, pain, and possible pathological fracture, often with an aggressive lytic and destructive mass on imaging.
- Micro: Histologically, [...] is characterized by a biphasic pattern of small, uniform, round to spindle-shaped cells and well-differentiated cartilage lobules.
- Ancillary: [...] shows diffuse strong membrane positivity for CD99 and nuclear SOX9 immunoreactivity.
Reference Gallery:
Mesenchymal chondrosarcoma. The characteristic histological feature is a bimorphic pattern: small, uniform, round to spindle-shaped cells with a perivascular haemangiopericytoma–like pattern and admixed cartilaginous tissue.
Mesenchymal chondrosarcoma. At low magnification, the characteristic histological feature is small, uniform, round to spindle-shaped cells that resemble Ewing sarcoma, with a perivascular haemangiopericytoma–like pattern, necrosis, and mineralization in cartilage islands.
Mesenchymal chondrosarcoma. Immunohistochemistry includes diffuse strong membrane positivity for CD99 on the mesenchymal small cell component.
Mesenchymal chondrosarcoma. Nuclear SOX9 immunoreactivity has a patchy distribution in both the small cell and chondroid components.
Mesenchymal chondrosarcoma. An aggressive tumour of the nasal cavity infiltrating the surrounding structures, with cortical destruction and patchy internal mineralization. CT, coronal reconstruction.
A: Mesenchymal Chondrosarcoma; Mesenchymal Chondrosarcoma; Mesenchymal Chondrosarcoma

Q: Conventional Osteosarcoma of the jaw is microscopically characterized by highly atypical cells producing an immature and often [...] neoplastic osteoid.
Osteosarcoma of the jaw. Conventional type. Moderately atypical spindle cells displaying an irregular and partly lace-like osteoid formation.
Conventional chondroblastic osteosarcoma. Dense tumour proliferation with lace-like osteoid formation and permeative growth.
A: lace-like
Q: Osteosarcoma of the jaw
- Clinical: The most frequent clinical manifestation of [...] is local swelling, often associated with pain and ulceration, and loosening of adjacent teeth.
- Micro: Conventional osteosarcoma of the jaw is defined by highly atypical cells producing an immature and often lace-like neoplastic osteoid.
- Ancillary: Positive staining with antibodies against [...] and [...] might aid in distinguishing low-grade osteosarcoma from benign fibro-osseous mimics.
Reference Gallery:
Osteosarcoma of the jaw. Conventional fibroblastic osteosarcoma. Highly pleomorphic spindle cells resembling fibrosarcoma.
Osteosarcoma of the jaw. Conventional type. Moderately atypical spindle cells displaying an irregular and partly lace-like osteoid formation.
Conventional chondroblastic osteosarcoma. A well-delineated tumour showing a cambium-like proliferative and hypercellular layer at the periphery, directly adjacent to soft tissue.
Conventional chondroblastic osteosarcoma. Dense tumour proliferation with lace-like osteoid formation and permeative growth.
Osteosarcoma, chondroblastic type. A tumour affecting the maxilla with infiltration of the adjacent soft tissue and mucosa, on the buccal aspect showing the parallel trabeculae of bone that produce the sunray appearance radiologically.
Osteosarcoma of the jaw. Conventional type. CT, axial view, showing a large and densely mineralized tumour expanding and destroying the right mandible.
Osteosarcoma. A painful swelling on the hard palate around the posterior teeth in a 33-year-old woman, a typical expansion without clinical features of malignancy.
Osteosarcoma of the jaw. Cone-beam CT, axial view, displaying a destructive osteosarcoma of the left maxilla with moderate internal mineralization.
A: osteosarcoma of the jaw; MDM2; CDK4

Q: In Osteosarcoma of the jaw, parallel trabeculae of bone infiltrating the adjacent soft tissue can produce a characteristic [...] appearance radiologically.
Osteosarcoma, chondroblastic type. A tumour affecting the maxilla with infiltration of the adjacent soft tissue and mucosa, on the buccal aspect showing the parallel trabeculae of bone that produce the sunray appearance radiologically.
A: sunray
Q: Osteosarcoma of the jaw
- Clinical: The most frequent clinical manifestation of [...] is local swelling, often associated with pain and ulceration, and loosening of adjacent teeth.
- Micro: Conventional osteosarcoma of the jaw is defined by highly atypical cells producing an immature and often lace-like neoplastic osteoid.
- Ancillary: Positive staining with antibodies against [...] and [...] might aid in distinguishing low-grade osteosarcoma from benign fibro-osseous mimics.
Reference Gallery:
Osteosarcoma of the jaw. Conventional fibroblastic osteosarcoma. Highly pleomorphic spindle cells resembling fibrosarcoma.
Osteosarcoma of the jaw. Conventional type. Moderately atypical spindle cells displaying an irregular and partly lace-like osteoid formation.
Conventional chondroblastic osteosarcoma. A well-delineated tumour showing a cambium-like proliferative and hypercellular layer at the periphery, directly adjacent to soft tissue.
Conventional chondroblastic osteosarcoma. Dense tumour proliferation with lace-like osteoid formation and permeative growth.
Osteosarcoma, chondroblastic type. A tumour affecting the maxilla with infiltration of the adjacent soft tissue and mucosa, on the buccal aspect showing the parallel trabeculae of bone that produce the sunray appearance radiologically.
Osteosarcoma of the jaw. Conventional type. CT, axial view, showing a large and densely mineralized tumour expanding and destroying the right mandible.
Osteosarcoma. A painful swelling on the hard palate around the posterior teeth in a 33-year-old woman, a typical expansion without clinical features of malignancy.
Osteosarcoma of the jaw. Cone-beam CT, axial view, displaying a destructive osteosarcoma of the left maxilla with moderate internal mineralization.
A: osteosarcoma of the jaw; MDM2; CDK4

Q: Microscopically, Rhabdomyosarcoma with TFCP2 rearrangement characteristically displays a [...] morphology composed of admixed spindle cell and epithelioid components with abundant eosinophilic cytoplasm.
Rhabdomyosarcoma with TFCP2 rearrangement. Epithelioid component with tumour cells displaying abundant eosinophilic cytoplasm along with large vesicular nuclei.
Rhabdomyosarcoma with TFCP2 rearrangement. Mixed spindle cell and epithelioid components showing tumour cells with abundant eosinophilic cytoplasm, either globoid or elongated, forming short fascicles.
A: biphasic
Back Extra: Rhabdomyosarcoma with TFCP2 rearrangement
- Clinical: Patients present with a large, rapidly growing swelling, often with pain and signs of compression.
- Micro: TFCP2-RMSs are biphasic, with spindle cell and epithelioid areas, showing large nuclei with brisk mitotic activity and necrosis.
- Ancillary: Virtually all cases are positive for cytokeratins, desmin, myogenin, and MYOD1. ALK expression is variable.
Reference Gallery:
Rhabdomyosarcoma with TFCP2 rearrangement. Epithelioid component with tumour cells displaying abundant eosinophilic cytoplasm along with large vesicular nuclei.
Rhabdomyosarcoma with TFCP2 rearrangement. Mixed spindle cell and epithelioid components showing tumour cells with abundant eosinophilic cytoplasm, either globoid or elongated, forming short fascicles.
Rhabdomyosarcoma with TFCP2 rearrangement. Diffuse expression of keratin by tumour cells (AE1/AE3 immunohistochemistry).
Rhabdomyosarcoma with TFCP2 rearrangement. Diffuse nuclear expression of MYOD1 by tumour cells (MYOD1 immunohistochemistry).
Rhabdomyosarcoma with TFCP2 rearrangement. Strong expression of ALK by tumour cells. Detection is variable between antibody clones and this example is stained with the 1A4 clone.
Rhabdomyosarcoma with TFCP2 rearrangement. T1-weighted (left) and T2-weighted (right) MRI showing an osteolytic mass of the mandible with soft tissue extension.

Q: An important immunohistochemical feature of Rhabdomyosarcoma with TFCP2 rearrangement is the paradoxical, diffuse expression of [...] alongside skeletal muscle markers (e.g., MYOD1, desmin) and variable ALK positivity.
Rhabdomyosarcoma with TFCP2 rearrangement. Diffuse expression of keratin by tumour cells (AE1/AE3 immunohistochemistry).
Rhabdomyosarcoma with TFCP2 rearrangement. Diffuse nuclear expression of MYOD1 by tumour cells (MYOD1 immunohistochemistry).
Rhabdomyosarcoma with TFCP2 rearrangement. Strong expression of ALK by tumour cells. Detection is variable between antibody clones and this example is stained with the 1A4 clone.
A: cytokeratins
Back Extra: Rhabdomyosarcoma with TFCP2 rearrangement
- Clinical: Patients present with a large, rapidly growing swelling, often with pain and signs of compression.
- Micro: TFCP2-RMSs are biphasic, with spindle cell and epithelioid areas, showing large nuclei with brisk mitotic activity and necrosis.
- Ancillary: Virtually all cases are positive for cytokeratins, desmin, myogenin, and MYOD1. ALK expression is variable.
Reference Gallery:
Rhabdomyosarcoma with TFCP2 rearrangement. Epithelioid component with tumour cells displaying abundant eosinophilic cytoplasm along with large vesicular nuclei.
Rhabdomyosarcoma with TFCP2 rearrangement. Mixed spindle cell and epithelioid components showing tumour cells with abundant eosinophilic cytoplasm, either globoid or elongated, forming short fascicles.
Rhabdomyosarcoma with TFCP2 rearrangement. Diffuse expression of keratin by tumour cells (AE1/AE3 immunohistochemistry).
Rhabdomyosarcoma with TFCP2 rearrangement. Diffuse nuclear expression of MYOD1 by tumour cells (MYOD1 immunohistochemistry).
Rhabdomyosarcoma with TFCP2 rearrangement. Strong expression of ALK by tumour cells. Detection is variable between antibody clones and this example is stained with the 1A4 clone.
Rhabdomyosarcoma with TFCP2 rearrangement. T1-weighted (left) and T2-weighted (right) MRI showing an osteolytic mass of the mandible with soft tissue extension.

Q: Radiologically, Rhabdomyosarcoma with TFCP2 rearrangement classically presents as an [...] mass of the craniofacial bones (e.g., the mandible) with soft tissue extension.
Rhabdomyosarcoma with TFCP2 rearrangement. T1-weighted (left) and T2-weighted (right) MRI showing an osteolytic mass of the mandible with soft tissue extension.
A: osteolytic
Back Extra: Rhabdomyosarcoma with TFCP2 rearrangement
- Clinical: Patients present with a large, rapidly growing swelling, often with pain and signs of compression.
- Micro: TFCP2-RMSs are biphasic, with spindle cell and epithelioid areas, showing large nuclei with brisk mitotic activity and necrosis.
- Ancillary: Virtually all cases are positive for cytokeratins, desmin, myogenin, and MYOD1. ALK expression is variable.
Reference Gallery:
Rhabdomyosarcoma with TFCP2 rearrangement. Epithelioid component with tumour cells displaying abundant eosinophilic cytoplasm along with large vesicular nuclei.
Rhabdomyosarcoma with TFCP2 rearrangement. Mixed spindle cell and epithelioid components showing tumour cells with abundant eosinophilic cytoplasm, either globoid or elongated, forming short fascicles.
Rhabdomyosarcoma with TFCP2 rearrangement. Diffuse expression of keratin by tumour cells (AE1/AE3 immunohistochemistry).
Rhabdomyosarcoma with TFCP2 rearrangement. Diffuse nuclear expression of MYOD1 by tumour cells (MYOD1 immunohistochemistry).
Rhabdomyosarcoma with TFCP2 rearrangement. Strong expression of ALK by tumour cells. Detection is variable between antibody clones and this example is stained with the 1A4 clone.
Rhabdomyosarcoma with TFCP2 rearrangement. T1-weighted (left) and T2-weighted (right) MRI showing an osteolytic mass of the mandible with soft tissue extension.

Q: Histologically, Carcinoma cuniculatum is characterized by a distinctive, burrowing [...] lined by well-differentiated squamous epithelium with minimal atypia.
Carcinoma cuniculatum. A characteristic infiltrative labyrinthine network of keratin-filled crypts.
Carcinoma cuniculatum. No more than mild cytological atypia and keratin microabscess formation.
A: labyrinthine network of keratin-filled crypts
Back Extra: Carcinoma cuniculatum
- Clinical: Common symptoms include pain, swelling, mucosal ulceration, tooth mobility, and induration. The presence of sequestra or yellow keratinaceous discharge from oral or cutaneous fistulae may lead to misdiagnosis as osteomyelitis or abscess.
- Micro: Characterized by a burrowing labyrinthine network of well-differentiated squamous epithelium, forming interconnecting keratin-filled crypts. There is no more than mild nuclear atypia.
- Ancillary: No specific ancillary studies are required for diagnosis.
Reference Gallery:
Carcinoma cuniculatum. Macroscopic view of carcinoma cuniculatum infiltrating bone between tooth roots. The white tumour encloses necrotic bone. The apparently separate islands were contiguous in a different plane.
Carcinoma cuniculatum. A characteristic infiltrative labyrinthine network of keratin-filled crypts.
Carcinoma cuniculatum. Bone invasion with microsequestra.
Carcinoma cuniculatum. No more than mild cytological atypia and keratin microabscess formation.
Carcinoma cuniculatum. Panoramic radiograph showing a carcinoma cuniculatum in the posterior body of the mandible, producing a moth-eaten partial radiolucency with cortical preservation. The appearance can resemble osteomyelitis, particularly when sequestra are detected radiographically.

Q: Clinically and radiographically, Carcinoma cuniculatum frequently presents with bone invasion, sequestra, and occasionally a yellow keratinaceous discharge, leading to a common misdiagnosis of [...].
Carcinoma cuniculatum. Macroscopic view of carcinoma cuniculatum infiltrating bone between tooth roots. The white tumour encloses necrotic bone. The apparently separate islands were contiguous in a different plane.
Carcinoma cuniculatum. Bone invasion with microsequestra.
Carcinoma cuniculatum. Panoramic radiograph showing a carcinoma cuniculatum in the posterior body of the mandible, producing a moth-eaten partial radiolucency with cortical preservation. The appearance can resemble osteomyelitis, particularly when sequestra are detected radiographically.
A: osteomyelitis
Back Extra: Carcinoma cuniculatum
- Clinical: Common symptoms include pain, swelling, mucosal ulceration, tooth mobility, and induration. The presence of sequestra or yellow keratinaceous discharge from oral or cutaneous fistulae may lead to misdiagnosis as osteomyelitis or abscess.
- Micro: Characterized by a burrowing labyrinthine network of well-differentiated squamous epithelium, forming interconnecting keratin-filled crypts. There is no more than mild nuclear atypia.
- Ancillary: No specific ancillary studies are required for diagnosis.
Reference Gallery:
Carcinoma cuniculatum. Macroscopic view of carcinoma cuniculatum infiltrating bone between tooth roots. The white tumour encloses necrotic bone. The apparently separate islands were contiguous in a different plane.
Carcinoma cuniculatum. A characteristic infiltrative labyrinthine network of keratin-filled crypts.
Carcinoma cuniculatum. Bone invasion with microsequestra.
Carcinoma cuniculatum. No more than mild cytological atypia and keratin microabscess formation.
Carcinoma cuniculatum. Panoramic radiograph showing a carcinoma cuniculatum in the posterior body of the mandible, producing a moth-eaten partial radiolucency with cortical preservation. The appearance can resemble osteomyelitis, particularly when sequestra are detected radiographically.

Q: Microscopically, conventional Oral Squamous Cell Carcinoma features large nests of malignant cells with eosinophilic cytoplasm, prominent intercellular bridging, and the characteristic formation of [...].
Squamous cell carcinoma. Well-differentiated, keratinizing conventional type.
A: squamous pearls
Back Extra: Oral Squamous Cell Carcinoma
- Clinical: Oral squamous cell carcinoma (OSCC) is often asymptomatic in early stages but can present with pain, altered sensation, and restricted tongue movement or swallowing in advanced stages. Lesions can appear as white, red, or mixed red and white, flat, nodular, or mass lesions.
- Micro: Conventional keratinizing OSCCs contain large nests, cords, and islands of cells with pink cytoplasm, prominent intercellular bridging, round, often hyperchromatic nuclei, squamous pearls, and dyskeratotic cells. Higher-grade neoplasms show marked nuclear and cellular pleomorphism, nuclear hyperchromasia, and mitotic figures.
- Ancillary: Confirmatory evaluation by histology of incisional or excisional biopsies remains the gold standard for diagnosing OSCC. Immunohistochemistry using keratins (AE1/AE3), CK5/6, p63, and p40 can confirm epithelial and squamous differentiation.
Reference Gallery:
Oral squamous cell carcinoma. Estimated age-standardized incidence rates (ASRs, World Standard Population), per 100 000 person-years, of lip and oral cavity cancer in 2020 among both sexes (all ages).
Oral squamous cell carcinoma. Estimated age-standardized mortality rates (ASRs, World Standard Population), per 100 000 person-years, of lip and oral cavity cancer in 2020 among both sexes (all ages).
Squamous cell carcinoma. Oral cavity squamous cell carcinoma demonstrating perineural invasion.
Squamous cell carcinoma. Although the tumour appears to have a cohesive invading front, a detached tumour satellite > 1 mm from the main tumour is a worst pattern of invasion 5 and an adverse prognostic factor (see Table <<25609>>).
Squamous cell carcinoma. Worst pattern of invasion 3, composed of small groups of > 15 tumour cells and single infiltrating tumour cells associated with a desmoplastic stroma (see Table <<25609>>).
Squamous cell carcinoma. Mandibular medullary bone invasion by squamous cell carcinoma.
Squamous cell carcinoma. Well-differentiated, keratinizing conventional type.
Basaloid squamous cell carcinoma. Well-rounded nests of basaloid cells with peripheral palisading, frequent mitoses, and comedonecrosis.
Spindle cell squamous cell carcinoma. A haphazard collection of atypical spindled and pleomorphic cells with hyperchromatic nuclei, lacking obvious epithelial differentiation.
Acantholytic squamous cell carcinoma. Pseudoglandular structures with dyskeratotic cells and prominent acantholysis that results from a loss of epithelial cohesion.
Adenosquamous carcinoma. A blending of epithelial and glandular components with necrosis, mitoses, and marked cellular and nuclear pleomorphism.

Q: In cases of Oral Squamous Cell Carcinoma, adverse histologic prognostic factors that must be evaluated include perineural invasion and the [...] (e.g., detached tumor satellites greater than 1 mm from the main tumor mass).
Squamous cell carcinoma. Oral cavity squamous cell carcinoma demonstrating perineural invasion.
Squamous cell carcinoma. Although the tumour appears to have a cohesive invading front, a detached tumour satellite > 1 mm from the main tumour is a worst pattern of invasion 5 and an adverse prognostic factor (see Table <<25609>>).
A: worst pattern of invasion
Back Extra: Oral Squamous Cell Carcinoma
- Clinical: Oral squamous cell carcinoma (OSCC) is often asymptomatic in early stages but can present with pain, altered sensation, and restricted tongue movement or swallowing in advanced stages. Lesions can appear as white, red, or mixed red and white, flat, nodular, or mass lesions.
- Micro: Conventional keratinizing OSCCs contain large nests, cords, and islands of cells with pink cytoplasm, prominent intercellular bridging, round, often hyperchromatic nuclei, squamous pearls, and dyskeratotic cells. Higher-grade neoplasms show marked nuclear and cellular pleomorphism, nuclear hyperchromasia, and mitotic figures.
- Ancillary: Confirmatory evaluation by histology of incisional or excisional biopsies remains the gold standard for diagnosing OSCC. Immunohistochemistry using keratins (AE1/AE3), CK5/6, p63, and p40 can confirm epithelial and squamous differentiation.
Reference Gallery:
Oral squamous cell carcinoma. Estimated age-standardized incidence rates (ASRs, World Standard Population), per 100 000 person-years, of lip and oral cavity cancer in 2020 among both sexes (all ages).
Oral squamous cell carcinoma. Estimated age-standardized mortality rates (ASRs, World Standard Population), per 100 000 person-years, of lip and oral cavity cancer in 2020 among both sexes (all ages).
Squamous cell carcinoma. Oral cavity squamous cell carcinoma demonstrating perineural invasion.
Squamous cell carcinoma. Although the tumour appears to have a cohesive invading front, a detached tumour satellite > 1 mm from the main tumour is a worst pattern of invasion 5 and an adverse prognostic factor (see Table <<25609>>).
Squamous cell carcinoma. Worst pattern of invasion 3, composed of small groups of > 15 tumour cells and single infiltrating tumour cells associated with a desmoplastic stroma (see Table <<25609>>).
Squamous cell carcinoma. Mandibular medullary bone invasion by squamous cell carcinoma.
Squamous cell carcinoma. Well-differentiated, keratinizing conventional type.
Basaloid squamous cell carcinoma. Well-rounded nests of basaloid cells with peripheral palisading, frequent mitoses, and comedonecrosis.
Spindle cell squamous cell carcinoma. A haphazard collection of atypical spindled and pleomorphic cells with hyperchromatic nuclei, lacking obvious epithelial differentiation.
Acantholytic squamous cell carcinoma. Pseudoglandular structures with dyskeratotic cells and prominent acantholysis that results from a loss of epithelial cohesion.
Adenosquamous carcinoma. A blending of epithelial and glandular components with necrosis, mitoses, and marked cellular and nuclear pleomorphism.

Q: Clinically, a slowly growing, slightly exophytic white tumor that frequently erodes underlying bone and causes extensive local destruction is characteristic of [...].
Verrucous carcinoma. A large exophytic tumour with verrucous architecture blanketing the edentulous mandibular alveolar ridge and extending to the involve the vestibule and buccal mucosa.
A: Verrucous Carcinoma
Back Extra: Verrucous Carcinoma
- Clinical: Verrucous Carcinoma (VC) presents as a slowly growing, slightly exophytic white tumour, often eroding bones and causing extensive destruction if left untreated.
- Micro: VC is characterized by a broad-based, well-differentiated exophytic and endophytic squamous epithelial proliferation with marked surface keratinization and keratin plugging, and well-defined pushing borders.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Verrucous Carcinoma.
Reference Gallery:
Verrucous carcinoma with minimal invasive carcinoma. Examination of the whole specimen showed verrucous carcinoma with a focus of conventional squamous cell carcinoma.
Verrucous carcinoma. A large exophytic tumour with verrucous architecture blanketing the edentulous mandibular alveolar ridge and extending to the involve the vestibule and buccal mucosa.
Verrucous carcinoma. A broad-based, well-differentiated epithelial proliferation with marked papillary parakeratosis and keratin plugging. Verrucous carcinoma invades the stroma evenly with well-defined pushing borders, extending below the level of the adjacent epithelium.
Verrucous carcinoma. A bulbous, coalescing rete and an expanded spinous layer are present. A lichenoid immune response is often seen.
Verrucous carcinoma. A lack of cytological atypia with normal maturation is usually seen in verrucous carcinoma. Rarely, mitoses may be present in the basal/parabasal layer, but without atypical mitotic forms.

Q: Histologically, Verrucous Carcinoma is defined by a broad-based, well-differentiated squamous proliferation with prominent surface keratin plugging and well-defined [...].
Verrucous carcinoma. A broad-based, well-differentiated epithelial proliferation with marked papillary parakeratosis and keratin plugging. Verrucous carcinoma invades the stroma evenly with well-defined pushing borders, extending below the level of the adjacent epithelium.
A: pushing borders
Back Extra: Verrucous Carcinoma
- Clinical: Verrucous Carcinoma (VC) presents as a slowly growing, slightly exophytic white tumour, often eroding bones and causing extensive destruction if left untreated.
- Micro: VC is characterized by a broad-based, well-differentiated exophytic and endophytic squamous epithelial proliferation with marked surface keratinization and keratin plugging, and well-defined pushing borders.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Verrucous Carcinoma.
Reference Gallery:
Verrucous carcinoma with minimal invasive carcinoma. Examination of the whole specimen showed verrucous carcinoma with a focus of conventional squamous cell carcinoma.
Verrucous carcinoma. A large exophytic tumour with verrucous architecture blanketing the edentulous mandibular alveolar ridge and extending to the involve the vestibule and buccal mucosa.
Verrucous carcinoma. A broad-based, well-differentiated epithelial proliferation with marked papillary parakeratosis and keratin plugging. Verrucous carcinoma invades the stroma evenly with well-defined pushing borders, extending below the level of the adjacent epithelium.
Verrucous carcinoma. A bulbous, coalescing rete and an expanded spinous layer are present. A lichenoid immune response is often seen.
Verrucous carcinoma. A lack of cytological atypia with normal maturation is usually seen in verrucous carcinoma. Rarely, mitoses may be present in the basal/parabasal layer, but without atypical mitotic forms.

Q: Despite its locally destructive nature, the bulbous, coalescing rete pegs of Verrucous Carcinoma display normal maturation and characteristically lack significant [...].
Verrucous carcinoma. A bulbous, coalescing rete and an expanded spinous layer are present. A lichenoid immune response is often seen.
Verrucous carcinoma. A lack of cytological atypia with normal maturation is usually seen in verrucous carcinoma. Rarely, mitoses may be present in the basal/parabasal layer, but without atypical mitotic forms.
A: cytological atypia
Back Extra: Verrucous Carcinoma
- Clinical: Verrucous Carcinoma (VC) presents as a slowly growing, slightly exophytic white tumour, often eroding bones and causing extensive destruction if left untreated.
- Micro: VC is characterized by a broad-based, well-differentiated exophytic and endophytic squamous epithelial proliferation with marked surface keratinization and keratin plugging, and well-defined pushing borders.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Verrucous Carcinoma.
Reference Gallery:
Verrucous carcinoma with minimal invasive carcinoma. Examination of the whole specimen showed verrucous carcinoma with a focus of conventional squamous cell carcinoma.
Verrucous carcinoma. A large exophytic tumour with verrucous architecture blanketing the edentulous mandibular alveolar ridge and extending to the involve the vestibule and buccal mucosa.
Verrucous carcinoma. A broad-based, well-differentiated epithelial proliferation with marked papillary parakeratosis and keratin plugging. Verrucous carcinoma invades the stroma evenly with well-defined pushing borders, extending below the level of the adjacent epithelium.
Verrucous carcinoma. A bulbous, coalescing rete and an expanded spinous layer are present. A lichenoid immune response is often seen.
Verrucous carcinoma. A lack of cytological atypia with normal maturation is usually seen in verrucous carcinoma. Rarely, mitoses may be present in the basal/parabasal layer, but without atypical mitotic forms.

Q: Histologically, Multifocal Epithelial Hyperplasia exhibits prominent acanthosis, widened rete pegs, and characteristic [...] in the upper epithelium, which represent cytopathic viral nuclear damage.
Multifocal epithelial hyperplasia. Acanthotic epithelium with minimal superficial keratosis. Rete pegs show elongation and widening, with a tendency to coalesce. Cell maturation is well preserved.
Multifocal epithelial hyperplasia. Characteristic mitosoid bodies representing cytopathic viral nuclear damage.
A: mitosoid bodies
Back Extra: Multifocal Epithelial Hyperplasia
- Clinical: Patients with multifocal epithelial hyperplasia (MEH) typically present with multiple, painless, sessile papules that can coalesce into cobblestone plaques.
- Micro: Histologically, MEH shows prominent exophytic acanthosis, broad and confluent rete ridges, and characteristic mitosoid bodies in the upper epithelium.
- Ancillary: HPV subtypes 13 and 32 are commonly associated with MEH, and routine HPV detection is rarely required.
Reference Gallery:
Multifocal epithelial hyperplasia. Multiple coalescing papules on the retrocommissural mucosa in an 8-year-old boy.
Multifocal epithelial hyperplasia. Acanthotic epithelium with minimal superficial keratosis. Rete pegs show elongation and widening, with a tendency to coalesce. Cell maturation is well preserved.
Multifocal epithelial hyperplasia. Characteristic mitosoid bodies representing cytopathic viral nuclear damage.

Q: Patients with Multifocal Epithelial Hyperplasia typically present with multiple painless, sessile papules that coalesce into cobblestone plaques, a condition primarily associated with HPV subtypes [...].
Multifocal epithelial hyperplasia. Multiple coalescing papules on the retrocommissural mucosa in an 8-year-old boy.
A: 13 and 32
Back Extra: Multifocal Epithelial Hyperplasia
- Clinical: Patients with multifocal epithelial hyperplasia (MEH) typically present with multiple, painless, sessile papules that can coalesce into cobblestone plaques.
- Micro: Histologically, MEH shows prominent exophytic acanthosis, broad and confluent rete ridges, and characteristic mitosoid bodies in the upper epithelium.
- Ancillary: HPV subtypes 13 and 32 are commonly associated with MEH, and routine HPV detection is rarely required.
Reference Gallery:
Multifocal epithelial hyperplasia. Multiple coalescing papules on the retrocommissural mucosa in an 8-year-old boy.
Multifocal epithelial hyperplasia. Acanthotic epithelium with minimal superficial keratosis. Rete pegs show elongation and widening, with a tendency to coalesce. Cell maturation is well preserved.
Multifocal epithelial hyperplasia. Characteristic mitosoid bodies representing cytopathic viral nuclear damage.

Q: Characterized clinically by coalescing oral papules and histologically by broad rete ridges with pathognomonic mitosoid bodies, the precise diagnosis is [...].
Multifocal epithelial hyperplasia. Multiple coalescing papules on the retrocommissural mucosa in an 8-year-old boy.
Multifocal epithelial hyperplasia. Characteristic mitosoid bodies representing cytopathic viral nuclear damage.
A: Multifocal Epithelial Hyperplasia
Back Extra: Multifocal Epithelial Hyperplasia
- Clinical: Patients with multifocal epithelial hyperplasia (MEH) typically present with multiple, painless, sessile papules that can coalesce into cobblestone plaques.
- Micro: Histologically, MEH shows prominent exophytic acanthosis, broad and confluent rete ridges, and characteristic mitosoid bodies in the upper epithelium.
- Ancillary: HPV subtypes 13 and 32 are commonly associated with MEH, and routine HPV detection is rarely required.
Reference Gallery:
Multifocal epithelial hyperplasia. Multiple coalescing papules on the retrocommissural mucosa in an 8-year-old boy.
Multifocal epithelial hyperplasia. Acanthotic epithelium with minimal superficial keratosis. Rete pegs show elongation and widening, with a tendency to coalesce. Cell maturation is well preserved.
Multifocal epithelial hyperplasia. Characteristic mitosoid bodies representing cytopathic viral nuclear damage.

Q: A classic clinical presentation featuring a single ulcer located laterally near the junction of the hard and soft palate is highly characteristic of [...].
Necrotizing sialometaplasia. Palatal ulcer lateral to the midline.
A: necrotizing sialometaplasia
Back Extra: Necrotizing Sialometaplasia
- Clinical: Classic presentation is a single lateral ulcer near the junction of the hard and soft palate, often asymptomatic but may have a burning sensation or mild pain.
- Micro: Pre-existing salivary lobular architecture is preserved with acinar necrosis, ductal squamous metaplasia, and regenerative atypia.
- Ancillary: Not typically required, but follow-up is crucial to ensure proper healing and rule out other conditions.
Reference Gallery:
Necrotizing sialometaplasia. The lobular architecture of the minor salivary glands is preserved and also involves ducts. Smooth contours and regenerative atypia of the lobules is evident among a reactive myxocollagenous stroma.
Necrotizing sialometaplasia. Necrosis of acini (with loss of nuclei and cell borders) with squamous metaplasia. Lobular configuration is maintained.
Necrotizing sialometaplasia. Pseudoepitheliomatous hyperplasia and squamous metaplasia of residual ducts and acini. The lobular architecture of the glands is preserved, with the outlines of the necrosed residual acini. Inflammation is also present.
Necrotizing sialometaplasia. Palatal ulcer lateral to the midline.

Q: The histologic hallmark of necrotizing sialometaplasia is acinar necrosis and ductal squamous metaplasia with overall preservation of the underlying salivary [...].
Necrotizing sialometaplasia. The lobular architecture of the minor salivary glands is preserved and also involves ducts. Smooth contours and regenerative atypia of the lobules is evident among a reactive myxocollagenous stroma.
Necrotizing sialometaplasia. Necrosis of acini (with loss of nuclei and cell borders) with squamous metaplasia. Lobular configuration is maintained.
A: lobular architecture
Back Extra: Necrotizing Sialometaplasia
- Clinical: Classic presentation is a single lateral ulcer near the junction of the hard and soft palate, often asymptomatic but may have a burning sensation or mild pain.
- Micro: Pre-existing salivary lobular architecture is preserved with acinar necrosis, ductal squamous metaplasia, and regenerative atypia.
- Ancillary: Not typically required, but follow-up is crucial to ensure proper healing and rule out other conditions.
Reference Gallery:
Necrotizing sialometaplasia. The lobular architecture of the minor salivary glands is preserved and also involves ducts. Smooth contours and regenerative atypia of the lobules is evident among a reactive myxocollagenous stroma.
Necrotizing sialometaplasia. Necrosis of acini (with loss of nuclei and cell borders) with squamous metaplasia. Lobular configuration is maintained.
Necrotizing sialometaplasia. Pseudoepitheliomatous hyperplasia and squamous metaplasia of residual ducts and acini. The lobular architecture of the glands is preserved, with the outlines of the necrosed residual acini. Inflammation is also present.
Necrotizing sialometaplasia. Palatal ulcer lateral to the midline.

Q: In necrotizing sialometaplasia, the presence of [...] and squamous metaplasia of residual ducts can mimic squamous cell carcinoma, but the smooth contours and preserved lobular outlines confirm the reactive nature of the lesion.
Necrotizing sialometaplasia. Pseudoepitheliomatous hyperplasia and squamous metaplasia of residual ducts and acini. The lobular architecture of the glands is preserved, with the outlines of the necrosed residual acini. Inflammation is also present.
A: pseudoepitheliomatous hyperplasia
Back Extra: Necrotizing Sialometaplasia
- Clinical: Classic presentation is a single lateral ulcer near the junction of the hard and soft palate, often asymptomatic but may have a burning sensation or mild pain.
- Micro: Pre-existing salivary lobular architecture is preserved with acinar necrosis, ductal squamous metaplasia, and regenerative atypia.
- Ancillary: Not typically required, but follow-up is crucial to ensure proper healing and rule out other conditions.
Reference Gallery:
Necrotizing sialometaplasia. The lobular architecture of the minor salivary glands is preserved and also involves ducts. Smooth contours and regenerative atypia of the lobules is evident among a reactive myxocollagenous stroma.
Necrotizing sialometaplasia. Necrosis of acini (with loss of nuclei and cell borders) with squamous metaplasia. Lobular configuration is maintained.
Necrotizing sialometaplasia. Pseudoepitheliomatous hyperplasia and squamous metaplasia of residual ducts and acini. The lobular architecture of the glands is preserved, with the outlines of the necrosed residual acini. Inflammation is also present.
Necrotizing sialometaplasia. Palatal ulcer lateral to the midline.

Q: A rapidly growing, asymptomatic pigmented lesion most commonly presenting as diffuse melanin pigmentation on the buccal mucosa is characteristic of [...].
Oral melanoacanthoma. Diffuse melanin pigmentation in the buccal mucosa of rapid onset but otherwise asymptomatic.
A: oral melanoacanthoma
Back Extra: Oral melanoacanthoma
- Clinical: Oral melanoacanthoma typically presents as a rapidly growing, pigmented lesion on the buccal mucosa, which is usually asymptomatic but can be slightly raised.
- Micro: Histopathology shows acanthosis, dendritic melanocytes throughout the epithelium, and melanin deposition in the basal layer, with S100 immunohistochemistry highlighting the melanocytes.
- Ancillary: Mucosal melanoma is the primary differential diagnosis, distinguished by the absence of atypia, hyperchromatism, and invasive melanocytic nests in oral melanoacanthoma.
Reference Gallery:
Melanoacanthoma. Dendritic melanocytes within the intercellular spaces of the acanthotic epithelium may be seen, but S100 immunohistochemisty is helpful when they are scarce or lightly pigmented.
Melanoacanthoma. The dendritic melanocytes are highlighted by S100 immunohistochemisty.
Oral melanoacanthoma. Diffuse melanin pigmentation in the buccal mucosa of rapid onset but otherwise asymptomatic.
Oral melanoacanthoma of the buccal mucosa. Acanthosis of the epithelium is apparent, along with melanin deposition in the basal layer and dendritic melanocytes within the epithelium.

Q: Histologically, oral melanoacanthoma is characterized by epithelial acanthosis, melanin deposition in the basal layer, and the presence of numerous [...] dispersed throughout the epithelium.
Melanoacanthoma. Dendritic melanocytes within the intercellular spaces of the acanthotic epithelium may be seen, but S100 immunohistochemisty is helpful when they are scarce or lightly pigmented.
Oral melanoacanthoma of the buccal mucosa. Acanthosis of the epithelium is apparent, along with melanin deposition in the basal layer and dendritic melanocytes within the epithelium.
A: dendritic melanocytes
Back Extra: Oral melanoacanthoma
- Clinical: Oral melanoacanthoma typically presents as a rapidly growing, pigmented lesion on the buccal mucosa, which is usually asymptomatic but can be slightly raised.
- Micro: Histopathology shows acanthosis, dendritic melanocytes throughout the epithelium, and melanin deposition in the basal layer, with S100 immunohistochemistry highlighting the melanocytes.
- Ancillary: Mucosal melanoma is the primary differential diagnosis, distinguished by the absence of atypia, hyperchromatism, and invasive melanocytic nests in oral melanoacanthoma.
Reference Gallery:
Melanoacanthoma. Dendritic melanocytes within the intercellular spaces of the acanthotic epithelium may be seen, but S100 immunohistochemisty is helpful when they are scarce or lightly pigmented.
Melanoacanthoma. The dendritic melanocytes are highlighted by S100 immunohistochemisty.
Oral melanoacanthoma. Diffuse melanin pigmentation in the buccal mucosa of rapid onset but otherwise asymptomatic.
Oral melanoacanthoma of the buccal mucosa. Acanthosis of the epithelium is apparent, along with melanin deposition in the basal layer and dendritic melanocytes within the epithelium.

Q: When evaluating oral melanoacanthoma, immunohistochemical staining with [...] is highly useful to highlight the characteristic dendritic melanocytes within the intercellular spaces of the epithelium.
Melanoacanthoma. The dendritic melanocytes are highlighted by S100 immunohistochemisty.
A: S100
Back Extra: Oral melanoacanthoma
- Clinical: Oral melanoacanthoma typically presents as a rapidly growing, pigmented lesion on the buccal mucosa, which is usually asymptomatic but can be slightly raised.
- Micro: Histopathology shows acanthosis, dendritic melanocytes throughout the epithelium, and melanin deposition in the basal layer, with S100 immunohistochemistry highlighting the melanocytes.
- Ancillary: Mucosal melanoma is the primary differential diagnosis, distinguished by the absence of atypia, hyperchromatism, and invasive melanocytic nests in oral melanoacanthoma.
Reference Gallery:
Melanoacanthoma. Dendritic melanocytes within the intercellular spaces of the acanthotic epithelium may be seen, but S100 immunohistochemisty is helpful when they are scarce or lightly pigmented.
Melanoacanthoma. The dendritic melanocytes are highlighted by S100 immunohistochemisty.
Oral melanoacanthoma. Diffuse melanin pigmentation in the buccal mucosa of rapid onset but otherwise asymptomatic.
Oral melanoacanthoma of the buccal mucosa. Acanthosis of the epithelium is apparent, along with melanin deposition in the basal layer and dendritic melanocytes within the epithelium.

Q: Histologically, [...] is typically characterized by a dysplastic epithelium covered by a brightly eosinophilic layer of parakeratin, accompanied by numerous karyorrhectic and apoptotic cells.
HPV-associated oral epithelial dysplasia. Dysplastic epithelium with a brightly eosinophilic keratin surface and basaloid morphology.
HPV-associated dysplasia. Marked architectural and cytological changes of dysplasia with karyorrhectic and apoptotic cells.
A: HPV-associated oral epithelial dysplasia
Back Extra: HPV-associated oral epithelial dysplasia
- Clinical: Patients with HPV-associated oral epithelial dysplasia (HPVOED) present with white, red/white, or red patches, which are usually flat and demarcated, with a male predilection (M:F ratio: 6:1).
- Micro: The epithelial surface is often covered by a brightly eosinophilic layer of parakeratin, with marked architectural and cytological changes, including karyorrhectic and apoptotic cells.
- Ancillary: Strong and diffuse nuclear and cytoplasmic p16 immunoreactivity is a characteristic finding, and high-risk HPV should be confirmed using DNA or RNA in situ hybridization.
Reference Gallery:
HPV-associated oral epithelial dysplasia. Dysplastic epithelium with a brightly eosinophilic keratin surface and basaloid morphology.
HPV-associated dysplasia. Marked architectural and cytological changes of dysplasia with karyorrhectic and apoptotic cells.
HPV-associated dysplasia. The epithelium shows full-thickness intense cytoplasmic and nuclear immunoreactivity for p16.
HPV-associated dysplasia. RNA in situ hybridization for high-risk HPV shows punctate, dot-like nuclear staining.
HPV-associated oral epithelial dysplasia. Marked architectural and cytological changes of dysplasia, with karyorrhectic and apoptotic cells.

Q: A characteristic immunohistochemical finding in HPV-associated oral epithelial dysplasia is strong and diffuse full-thickness nuclear and cytoplasmic expression of [...].
HPV-associated dysplasia. The epithelium shows full-thickness intense cytoplasmic and nuclear immunoreactivity for p16.
A: p16
Back Extra: HPV-associated oral epithelial dysplasia
- Clinical: Patients with HPV-associated oral epithelial dysplasia (HPVOED) present with white, red/white, or red patches, which are usually flat and demarcated, with a male predilection (M:F ratio: 6:1).
- Micro: The epithelial surface is often covered by a brightly eosinophilic layer of parakeratin, with marked architectural and cytological changes, including karyorrhectic and apoptotic cells.
- Ancillary: Strong and diffuse nuclear and cytoplasmic p16 immunoreactivity is a characteristic finding, and high-risk HPV should be confirmed using DNA or RNA in situ hybridization.
Reference Gallery:
HPV-associated oral epithelial dysplasia. Dysplastic epithelium with a brightly eosinophilic keratin surface and basaloid morphology.
HPV-associated dysplasia. Marked architectural and cytological changes of dysplasia with karyorrhectic and apoptotic cells.
HPV-associated dysplasia. The epithelium shows full-thickness intense cytoplasmic and nuclear immunoreactivity for p16.
HPV-associated dysplasia. RNA in situ hybridization for high-risk HPV shows punctate, dot-like nuclear staining.
HPV-associated oral epithelial dysplasia. Marked architectural and cytological changes of dysplasia, with karyorrhectic and apoptotic cells.

Q: Ancillary testing for HPV-associated oral epithelial dysplasia using RNA in situ hybridization typically demonstrates punctate, dot-like nuclear staining to confirm the presence of [...].
HPV-associated dysplasia. RNA in situ hybridization for high-risk HPV shows punctate, dot-like nuclear staining.
A: high-risk HPV
Back Extra: HPV-associated oral epithelial dysplasia
- Clinical: Patients with HPV-associated oral epithelial dysplasia (HPVOED) present with white, red/white, or red patches, which are usually flat and demarcated, with a male predilection (M:F ratio: 6:1).
- Micro: The epithelial surface is often covered by a brightly eosinophilic layer of parakeratin, with marked architectural and cytological changes, including karyorrhectic and apoptotic cells.
- Ancillary: Strong and diffuse nuclear and cytoplasmic p16 immunoreactivity is a characteristic finding, and high-risk HPV should be confirmed using DNA or RNA in situ hybridization.
Reference Gallery:
HPV-associated oral epithelial dysplasia. Dysplastic epithelium with a brightly eosinophilic keratin surface and basaloid morphology.
HPV-associated dysplasia. Marked architectural and cytological changes of dysplasia with karyorrhectic and apoptotic cells.
HPV-associated dysplasia. The epithelium shows full-thickness intense cytoplasmic and nuclear immunoreactivity for p16.
HPV-associated dysplasia. RNA in situ hybridization for high-risk HPV shows punctate, dot-like nuclear staining.
HPV-associated oral epithelial dysplasia. Marked architectural and cytological changes of dysplasia, with karyorrhectic and apoptotic cells.

Q: In Oral Epithelial Dysplasia, hallmark architectural abnormalities include loss of basal cell polarity, premature keratinization, and the formation of [...] rete processes.
Oral epithelial dysplasia, moderate. Drop-shaped rete processes with increased mitotic figures, reduced keratinocyte cohesion, and abnormal variation in nuclear size, extending to the spinous layer.
Oral epithelial dysplasia, mild. Primarily an architectural or differentiated pattern of dysplasia with loss of basal cell polarization, budding of the rete, increased hyperchromasia, and mitotic figures confined to the basal and parabasal layers with generalized premature keratinization.
A: drop-shaped
Back Extra: Oral Epithelial Dysplasia
- Clinical: Oral epithelial dysplasia (OED) is often asymptomatic and is diagnosed through biopsy of oral potentially malignant disorders (OPMDs) like erythroplakia and erythroleukoplakia.
- Micro: OED is characterized by architectural and cytological atypia, including loss of basal cell polarity, increased mitotic figures, and premature keratinization.
- Ancillary: Diagnosis of OED does not rely on ancillary studies; it is primarily based on histopathological examination.
Reference Gallery:
Oral epithelial dysplasia, moderate. Drop-shaped rete processes with increased mitotic figures, reduced keratinocyte cohesion, and abnormal variation in nuclear size, extending to the spinous layer.
Oral epithelial dysplasia, severe. Increased keratinization, loss of cohesion in the prickle cell layer, and increased numbers of basaloid cells with mild hyperchromatism and anisonucleosis with budding and downward growth.
Oral epithelial dysplasia, severe. Loss of basal cell polarity, epithelial differentiation, increased mitotic figures, and abnormal variation in nuclear and cellular features extending throughout the full epithelial thickness.
Oral epithelial dysplasia, mild. Band-like inflammatory infiltrate at the epithelial–stromal interface imparting a lichenoid appearance including apoptotic degeneration of keratinocytes but with general preservation of a slightly expanded and hyperchromatic basal cell layer.
Oral epithelial dysplasia, moderate. Band-like inflammatory infiltrate at the epithelial–stromal interface imparts a lichenoid appearance, but loss of basal cell polarization, nuclear hyperchromasia, and mitoses extending to the mid-third of the atrophic epithelium excludes oral lichen planus.
Oral epithelial dysplasia, mild. Primarily an architectural or differentiated pattern of dysplasia with loss of basal cell polarization, budding of the rete, increased hyperchromasia, and mitotic figures confined to the basal and parabasal layers with generalized premature keratinization.
Oral epithelial dysplasia, mild. Architectural features of dysplasia include a sharp lateral demarcation of the epithelium with an abrupt change to orthokeratosis. Mild anisonucleosis and hyperchromatism, as well as a slightly disorganized basal cell layer with generalized premature keratinization, are seen.

Q: Some cases of Oral Epithelial Dysplasia feature a band-like inflammatory infiltrate that mimics [...], but can be distinguished by the presence of true cytological atypia, loss of basal cell polarization, and suprabasal mitoses.
Oral epithelial dysplasia, mild. Band-like inflammatory infiltrate at the epithelial–stromal interface imparting a lichenoid appearance including apoptotic degeneration of keratinocytes but with general preservation of a slightly expanded and hyperchromatic basal cell layer.
Oral epithelial dysplasia, moderate. Band-like inflammatory infiltrate at the epithelial–stromal interface imparts a lichenoid appearance, but loss of basal cell polarization, nuclear hyperchromasia, and mitoses extending to the mid-third of the atrophic epithelium excludes oral lichen planus.
A: oral lichen planus
Back Extra: Oral Epithelial Dysplasia
- Clinical: Oral epithelial dysplasia (OED) is often asymptomatic and is diagnosed through biopsy of oral potentially malignant disorders (OPMDs) like erythroplakia and erythroleukoplakia.
- Micro: OED is characterized by architectural and cytological atypia, including loss of basal cell polarity, increased mitotic figures, and premature keratinization.
- Ancillary: Diagnosis of OED does not rely on ancillary studies; it is primarily based on histopathological examination.
Reference Gallery:
Oral epithelial dysplasia, moderate. Drop-shaped rete processes with increased mitotic figures, reduced keratinocyte cohesion, and abnormal variation in nuclear size, extending to the spinous layer.
Oral epithelial dysplasia, severe. Increased keratinization, loss of cohesion in the prickle cell layer, and increased numbers of basaloid cells with mild hyperchromatism and anisonucleosis with budding and downward growth.
Oral epithelial dysplasia, severe. Loss of basal cell polarity, epithelial differentiation, increased mitotic figures, and abnormal variation in nuclear and cellular features extending throughout the full epithelial thickness.
Oral epithelial dysplasia, mild. Band-like inflammatory infiltrate at the epithelial–stromal interface imparting a lichenoid appearance including apoptotic degeneration of keratinocytes but with general preservation of a slightly expanded and hyperchromatic basal cell layer.
Oral epithelial dysplasia, moderate. Band-like inflammatory infiltrate at the epithelial–stromal interface imparts a lichenoid appearance, but loss of basal cell polarization, nuclear hyperchromasia, and mitoses extending to the mid-third of the atrophic epithelium excludes oral lichen planus.
Oral epithelial dysplasia, mild. Primarily an architectural or differentiated pattern of dysplasia with loss of basal cell polarization, budding of the rete, increased hyperchromasia, and mitotic figures confined to the basal and parabasal layers with generalized premature keratinization.
Oral epithelial dysplasia, mild. Architectural features of dysplasia include a sharp lateral demarcation of the epithelium with an abrupt change to orthokeratosis. Mild anisonucleosis and hyperchromatism, as well as a slightly disorganized basal cell layer with generalized premature keratinization, are seen.

Q: In Oral Potentially Malignant Disorders, the most common clinical presentation is a persistent white mucosal patch or plaque (often seen on the tongue), clinically termed [...].
Oral leukoplakia. Large leukoplakia on the lateral and ventral tongue. Some margins are well defined but fade to normal posteriorly.
Oral leukoplakia. Depressed lesion on the lateral tongue with light keratosis around the periphery and zones of keratosis within it, together with mucosa with a lightly stippled surface. Biopsy showed moderate dysplasia.
A: leukoplakia
Back Extra: Oral Potentially Malignant Disorders
- Clinical: Oral Potentially Malignant Disorders (OPMDs) often present as red, white, or speckled lesions, with leukoplakia and erythroplakia being the most common types.
- Micro: The histopathological hallmark of OPMDs is the presence and degree of oral epithelial dysplasia, which can range from minimal to severe.
- Ancillary: Ancillary studies are generally not clinically relevant for the diagnosis of OPMDs.
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Erythroleukoplakia. A mixed red and white patch on the lateral tongue. The leukoplakia component is non-homogeneous, with nodular keratotic areas.
Erythroplakia. An irregular, flat, fiery-red patch of the lateral tongue. Severe dysplasia was present on biopsy.
Oral leukoplakia. Large leukoplakia on the lateral and ventral tongue. Some margins are well defined but fade to normal posteriorly.
Oral leukoplakia. Depressed lesion on the lateral tongue with light keratosis around the periphery and zones of keratosis within it, together with mucosa with a lightly stippled surface. Biopsy showed moderate dysplasia.

Q: In Oral Potentially Malignant Disorders, irregular, fiery-red mucosal patches that frequently harbor severe dysplasia are clinically termed [...].
Erythroplakia. An irregular, flat, fiery-red patch of the lateral tongue. Severe dysplasia was present on biopsy.
A: erythroplakia
Back Extra: Oral Potentially Malignant Disorders
- Clinical: Oral Potentially Malignant Disorders (OPMDs) often present as red, white, or speckled lesions, with leukoplakia and erythroplakia being the most common types.
- Micro: The histopathological hallmark of OPMDs is the presence and degree of oral epithelial dysplasia, which can range from minimal to severe.
- Ancillary: Ancillary studies are generally not clinically relevant for the diagnosis of OPMDs.
Reference Gallery:
Erythroleukoplakia. A mixed red and white patch on the lateral tongue. The leukoplakia component is non-homogeneous, with nodular keratotic areas.
Erythroplakia. An irregular, flat, fiery-red patch of the lateral tongue. Severe dysplasia was present on biopsy.
Oral leukoplakia. Large leukoplakia on the lateral and ventral tongue. Some margins are well defined but fade to normal posteriorly.
Oral leukoplakia. Depressed lesion on the lateral tongue with light keratosis around the periphery and zones of keratosis within it, together with mucosa with a lightly stippled surface. Biopsy showed moderate dysplasia.

Q: In Oral Potentially Malignant Disorders, mixed red and white speckled patches on the oral mucosa are clinically designated as [...].
Erythroleukoplakia. A mixed red and white patch on the lateral tongue. The leukoplakia component is non-homogeneous, with nodular keratotic areas.
A: erythroleukoplakia
Back Extra: Oral Potentially Malignant Disorders
- Clinical: Oral Potentially Malignant Disorders (OPMDs) often present as red, white, or speckled lesions, with leukoplakia and erythroplakia being the most common types.
- Micro: The histopathological hallmark of OPMDs is the presence and degree of oral epithelial dysplasia, which can range from minimal to severe.
- Ancillary: Ancillary studies are generally not clinically relevant for the diagnosis of OPMDs.
Reference Gallery:
Erythroleukoplakia. A mixed red and white patch on the lateral tongue. The leukoplakia component is non-homogeneous, with nodular keratotic areas.
Erythroplakia. An irregular, flat, fiery-red patch of the lateral tongue. Severe dysplasia was present on biopsy.
Oral leukoplakia. Large leukoplakia on the lateral and ventral tongue. Some margins are well defined but fade to normal posteriorly.
Oral leukoplakia. Depressed lesion on the lateral tongue with light keratosis around the periphery and zones of keratosis within it, together with mucosa with a lightly stippled surface. Biopsy showed moderate dysplasia.

Q: Clinically, Proliferative Verrucous Leukoplakia often presents as spreading, smooth to fissured or verruciform white patches that frequently mimic oral [...] or homogeneous leukoplakias.
Proliferative verrucous leukoplakia. A well-demarcated leukoplakia with a prominent linear marginal pattern common to proliferative verrucous leukoplakia lesions involving the gingiva.
Proliferative verrucous leukoplakia. Diffuse, rough, variably thickened leukoplakia with prominent fissuring and indistinct borders.
A: lichen planus
Back Extra: Proliferative Verrucous Leukoplakia
- Clinical: Proliferative Verrucous Leukoplakia (PVL) often presents as indistinguishable from oral lichen planus or homogeneous oral leukoplakias, forming smooth to fissured/verruciform white or mixed white-and-red patches.
- Micro: Early lesions of PVL are unremarkable flat keratoses with architectural features that may be atypical, such as premature keratinization and sharp lateral margins.
- Ancillary: PVL is best managed by active patient surveillance, with biopsy when clinically indicated.
Reference Gallery:
Proliferative verrucous leukoplakia. A well-demarcated leukoplakia with a prominent linear marginal pattern common to proliferative verrucous leukoplakia lesions involving the gingiva.
Proliferative verrucous leukoplakia. Diffuse, rough, variably thickened leukoplakia with prominent fissuring and indistinct borders.
Early lesions of proliferative verrucous leukoplakia. Abrupt transition to marked hyperorthokeratosis and epithelial corrugation with lichenoid inflammation.
Early lesions of proliferative verrucous leukoplakia. Sharp transitions and skip zones of corrugated orthokeratosis.
Proliferative verrucous leukoplakia. Bulky hyperkeratotic endophytic proliferation with lichenoid inflammation. Bulky endophytic proliferative epithelium showing bland cells with broad, blunted rete pegs that appear to merge towards one another as they attain a uniform depth.
Proliferative verrucous leukoplakia. Bulky hyperkeratotic proliferation with lichenoid inflammation. An exophytic and endophytic growth pattern covered by parakeratin, with an undulating surface and surface crypts filled with parakeratin.
Proliferative verrucous leukoplakia. Early lesion exhibiting subtle histology with orthokeratosis, epithelial atrophy, no cytological atypia, and variable or no inflammation.

Q: Early microscopic lesions of Proliferative Verrucous Leukoplakia frequently exhibit an unremarkable flat keratosis with architectural atypia, classically demonstrating a sharp, [...] to marked hyperorthokeratosis and epithelial corrugation.
Early lesions of proliferative verrucous leukoplakia. Abrupt transition to marked hyperorthokeratosis and epithelial corrugation with lichenoid inflammation.
Early lesions of proliferative verrucous leukoplakia. Sharp transitions and skip zones of corrugated orthokeratosis.
A: abrupt transition
Back Extra: Proliferative Verrucous Leukoplakia
- Clinical: Proliferative Verrucous Leukoplakia (PVL) often presents as indistinguishable from oral lichen planus or homogeneous oral leukoplakias, forming smooth to fissured/verruciform white or mixed white-and-red patches.
- Micro: Early lesions of PVL are unremarkable flat keratoses with architectural features that may be atypical, such as premature keratinization and sharp lateral margins.
- Ancillary: PVL is best managed by active patient surveillance, with biopsy when clinically indicated.
Reference Gallery:
Proliferative verrucous leukoplakia. A well-demarcated leukoplakia with a prominent linear marginal pattern common to proliferative verrucous leukoplakia lesions involving the gingiva.
Proliferative verrucous leukoplakia. Diffuse, rough, variably thickened leukoplakia with prominent fissuring and indistinct borders.
Early lesions of proliferative verrucous leukoplakia. Abrupt transition to marked hyperorthokeratosis and epithelial corrugation with lichenoid inflammation.
Early lesions of proliferative verrucous leukoplakia. Sharp transitions and skip zones of corrugated orthokeratosis.
Proliferative verrucous leukoplakia. Bulky hyperkeratotic endophytic proliferation with lichenoid inflammation. Bulky endophytic proliferative epithelium showing bland cells with broad, blunted rete pegs that appear to merge towards one another as they attain a uniform depth.
Proliferative verrucous leukoplakia. Bulky hyperkeratotic proliferation with lichenoid inflammation. An exophytic and endophytic growth pattern covered by parakeratin, with an undulating surface and surface crypts filled with parakeratin.
Proliferative verrucous leukoplakia. Early lesion exhibiting subtle histology with orthokeratosis, epithelial atrophy, no cytological atypia, and variable or no inflammation.

Q: In more advanced, bulky lesions of Proliferative Verrucous Leukoplakia, the epithelium shows a hyperkeratotic endophytic proliferation with bland cytology and broad, blunted [...] that appear to merge toward one another at a uniform depth.
Proliferative verrucous leukoplakia. Bulky hyperkeratotic endophytic proliferation with lichenoid inflammation. Bulky endophytic proliferative epithelium showing bland cells with broad, blunted rete pegs that appear to merge towards one another as they attain a uniform depth.
Proliferative verrucous leukoplakia. Bulky hyperkeratotic proliferation with lichenoid inflammation. An exophytic and endophytic growth pattern covered by parakeratin, with an undulating surface and surface crypts filled with parakeratin.
A: rete pegs
Back Extra: Proliferative Verrucous Leukoplakia
- Clinical: Proliferative Verrucous Leukoplakia (PVL) often presents as indistinguishable from oral lichen planus or homogeneous oral leukoplakias, forming smooth to fissured/verruciform white or mixed white-and-red patches.
- Micro: Early lesions of PVL are unremarkable flat keratoses with architectural features that may be atypical, such as premature keratinization and sharp lateral margins.
- Ancillary: PVL is best managed by active patient surveillance, with biopsy when clinically indicated.
Reference Gallery:
Proliferative verrucous leukoplakia. A well-demarcated leukoplakia with a prominent linear marginal pattern common to proliferative verrucous leukoplakia lesions involving the gingiva.
Proliferative verrucous leukoplakia. Diffuse, rough, variably thickened leukoplakia with prominent fissuring and indistinct borders.
Early lesions of proliferative verrucous leukoplakia. Abrupt transition to marked hyperorthokeratosis and epithelial corrugation with lichenoid inflammation.
Early lesions of proliferative verrucous leukoplakia. Sharp transitions and skip zones of corrugated orthokeratosis.
Proliferative verrucous leukoplakia. Bulky hyperkeratotic endophytic proliferation with lichenoid inflammation. Bulky endophytic proliferative epithelium showing bland cells with broad, blunted rete pegs that appear to merge towards one another as they attain a uniform depth.
Proliferative verrucous leukoplakia. Bulky hyperkeratotic proliferation with lichenoid inflammation. An exophytic and endophytic growth pattern covered by parakeratin, with an undulating surface and surface crypts filled with parakeratin.
Proliferative verrucous leukoplakia. Early lesion exhibiting subtle histology with orthokeratosis, epithelial atrophy, no cytological atypia, and variable or no inflammation.

Q: Clinically, patients with Submucous Fibrosis typically present with a leathery mucosa and palpable [...] in the buccal mucosa, lip, or palate, which leads to a progressive limitation of mouth opening.
Oral submucous fibrosis. Fibrous bands of buccal mucosa.
Oral submucous fibrosis. Palatal fibrosis and shrunken uvula.
A: fibrous bands
Back Extra: Submucous Fibrosis
- Clinical: Fibrous banding in the buccal mucosa, lip, or palate leads to a progressive limitation of mouth opening, often accompanied by burning mouth, depapillation of the tongue, and a leathery mucosa.
- Micro: Early stages show hyperplastic epithelium, which progresses to marked atrophy with loss of rete ridges and juxtaepithelial hyalinization. Advanced stages exhibit dense fibrosis and muscle degeneration.
- Ancillary: No established molecular predictive markers, but loss of heterozygosity in genes within the 13q14-q33 region may have some predictive value for malignant transformation.
Reference Gallery:
Oral submucous fibrosis. Fibrous bands of buccal mucosa.
Oral submucous fibrosis. Palatal fibrosis and shrunken uvula.
Oral submucous fibrosis. Epithelium showing dysplastic changes. The submucosa is fibrosed and contains a diffuse inflammatory cell infiltrate.
Oral submucous fibrosis. Marked epithelial atrophy, flattening of rete ridges, juxtaepithelial hyalinization, and homogeneous collagen.
Oral submucous fibrosis. An advanced case showing fibrosis involving muscles, muscle degeneration, and foci of chronic inflammatory cells.
Map showing countries reporting areca nut consumption. Legend text not found

Q: Microscopically, established cases of Submucous Fibrosis are characterized by marked epithelial atrophy, loss of rete ridges, dense collagen deposition, and characteristic [...].
Oral submucous fibrosis. Marked epithelial atrophy, flattening of rete ridges, juxtaepithelial hyalinization, and homogeneous collagen.
A: juxtaepithelial hyalinization
Back Extra: Submucous Fibrosis
- Clinical: Fibrous banding in the buccal mucosa, lip, or palate leads to a progressive limitation of mouth opening, often accompanied by burning mouth, depapillation of the tongue, and a leathery mucosa.
- Micro: Early stages show hyperplastic epithelium, which progresses to marked atrophy with loss of rete ridges and juxtaepithelial hyalinization. Advanced stages exhibit dense fibrosis and muscle degeneration.
- Ancillary: No established molecular predictive markers, but loss of heterozygosity in genes within the 13q14-q33 region may have some predictive value for malignant transformation.
Reference Gallery:
Oral submucous fibrosis. Fibrous bands of buccal mucosa.
Oral submucous fibrosis. Palatal fibrosis and shrunken uvula.
Oral submucous fibrosis. Epithelium showing dysplastic changes. The submucosa is fibrosed and contains a diffuse inflammatory cell infiltrate.
Oral submucous fibrosis. Marked epithelial atrophy, flattening of rete ridges, juxtaepithelial hyalinization, and homogeneous collagen.
Oral submucous fibrosis. An advanced case showing fibrosis involving muscles, muscle degeneration, and foci of chronic inflammatory cells.
Map showing countries reporting areca nut consumption. Legend text not found

Q: Clinically, Congenital Granular Cell Epulis typically presents in newborns as a lobulated soft tissue mass emerging from the [...].
Congenital granular cell epulis. A newborn girl with a sessile lobulated pink mass of the maxillary alveolar process measuring several centimetres in diameter. The mass interferes with feeding.
A: maxillary alveolar ridge
Back Extra: Congenital Granular Cell Epulis
- Clinical: Congenital granular cell epulis typically presents as a pedunculated soft tissue mass on the maxillary alveolar ridge in newborns, which can interfere with feeding and respiration.
- Micro: The lesion is well-circumscribed, with tightly packed polygonal cells having abundant granular cytoplasm and eccentric dark nuclei, without mitosis.
- Ancillary: Immunohistochemistry shows positivity for vimentin, NSE, laminin, and variability with histiocytic markers; negative for muscle markers, SOX10, and S100.
Reference Gallery:
Congenital granular cell epulis. A newborn girl with a sessile lobulated pink mass of the maxillary alveolar process measuring several centimetres in diameter. The mass interferes with feeding.
Congenital granular cell epulis. A well-circumscribed lesion beneath an attenuated epithelium that lacks rete ridges. An uninvolved zone of lamina propria separates the lesion from the epithelium. The lesion is composed of tightly packed polygonal cells with abundant granular cytoplasm. Nuclei are eccentric and dark-staining, with inconspicuous nucleoli and no evidence of mitotic activity. Thin-walled vessels are distributed throughout the lesion (inset).

Q: Microscopically, Congenital Granular Cell Epulis consists of tightly packed polygonal cells with abundant [...], which are characteristically separated from the overlying attenuated epithelium by an uninvolved zone of lamina propria.
Congenital granular cell epulis. A well-circumscribed lesion beneath an attenuated epithelium that lacks rete ridges. An uninvolved zone of lamina propria separates the lesion from the epithelium. The lesion is composed of tightly packed polygonal cells with abundant granular cytoplasm. Nuclei are eccentric and dark-staining, with inconspicuous nucleoli and no evidence of mitotic activity. Thin-walled vessels are distributed throughout the lesion (inset).
A: granular cytoplasm
Back Extra: Congenital Granular Cell Epulis
- Clinical: Congenital granular cell epulis typically presents as a pedunculated soft tissue mass on the maxillary alveolar ridge in newborns, which can interfere with feeding and respiration.
- Micro: The lesion is well-circumscribed, with tightly packed polygonal cells having abundant granular cytoplasm and eccentric dark nuclei, without mitosis.
- Ancillary: Immunohistochemistry shows positivity for vimentin, NSE, laminin, and variability with histiocytic markers; negative for muscle markers, SOX10, and S100.
Reference Gallery:
Congenital granular cell epulis. A newborn girl with a sessile lobulated pink mass of the maxillary alveolar process measuring several centimetres in diameter. The mass interferes with feeding.
Congenital granular cell epulis. A well-circumscribed lesion beneath an attenuated epithelium that lacks rete ridges. An uninvolved zone of lamina propria separates the lesion from the epithelium. The lesion is composed of tightly packed polygonal cells with abundant granular cytoplasm. Nuclei are eccentric and dark-staining, with inconspicuous nucleoli and no evidence of mitotic activity. Thin-walled vessels are distributed throughout the lesion (inset).

Q: Despite its name, true [...] matrix is paradoxically rare and typically only focal in Ectomesenchymal Chondromyxoid Tumor.
Ectomesenchymal chondromyxoid tumour. Spindle cells arranged in loose fascicles and whorls, with myxohyaline stroma.
Ectomesenchymal chondromyxoid tumour. Hyaline cartilage matrix is paradoxically rare and, when present, is typically only focal.
A: hyaline cartilage
Back Extra: Ectomesenchymal Chondromyxoid Tumour
- Clinical: Ectomesenchymal chondromyxoid tumour presents as a slow-growing, painless mass in young adults, often with a duration ranging from months to years.
- Micro: The tumour is characterized by spindle to stellate cells arranged in sheets, fascicles, and reticular patterns within a myxoid to collagenous stroma.
- Ancillary: Immunohistochemistry shows diffuse expression of GFAP, and the presence of a RREB1::MRTFB fusion is diagnostically helpful.
Reference Gallery:
Ectomesenchymal chondromyxoid tumour. Spindle cells arranged in loose fascicles and whorls, with myxohyaline stroma.
Ectomesenchymal chondromyxoid tumour. Stellate cells with a reticular pattern and abundant myxoid stroma.
Ectomesenchymal chondromyxoid tumour. Locally aggressive features, such as bone involvement, are uncommon.
Ectomesenchymal chondromyxoid tumour. Most tumours express GFAP.
Ectomesenchymal chondromyxoid tumour. Hyaline cartilage matrix is paradoxically rare and, when present, is typically only focal.

Q: Immunohistochemistry for Ectomesenchymal Chondromyxoid Tumor characteristically demonstrates diffuse expression of [...].
Ectomesenchymal chondromyxoid tumour. Most tumours express GFAP.
A: GFAP
Back Extra: Ectomesenchymal Chondromyxoid Tumour
- Clinical: Ectomesenchymal chondromyxoid tumour presents as a slow-growing, painless mass in young adults, often with a duration ranging from months to years.
- Micro: The tumour is characterized by spindle to stellate cells arranged in sheets, fascicles, and reticular patterns within a myxoid to collagenous stroma.
- Ancillary: Immunohistochemistry shows diffuse expression of GFAP, and the presence of a RREB1::MRTFB fusion is diagnostically helpful.
Reference Gallery:
Ectomesenchymal chondromyxoid tumour. Spindle cells arranged in loose fascicles and whorls, with myxohyaline stroma.
Ectomesenchymal chondromyxoid tumour. Stellate cells with a reticular pattern and abundant myxoid stroma.
Ectomesenchymal chondromyxoid tumour. Locally aggressive features, such as bone involvement, are uncommon.
Ectomesenchymal chondromyxoid tumour. Most tumours express GFAP.
Ectomesenchymal chondromyxoid tumour. Hyaline cartilage matrix is paradoxically rare and, when present, is typically only focal.

Q: The overlying mucosa in a Granular Cell Tumor frequently exhibits dramatic [...], which must not be erroneously interpreted as squamous cell carcinoma.
Granular cell tumour. Dramatic pseudoepitheliomatous hyperplasia of the overlying mucosa should not be erroneously interpreted as squamous cell carcinoma, and the unencapsulated mass of granular cells immediately beneath the epithelium should not be overlooked.
A: pseudoepitheliomatous hyperplasia
Back Extra: Granular Cell Tumor
- Clinical: Patients with granular cell tumour present with a non-tender, slowly enlarging, sessile mucosal to yellowish-coloured submucosal mass, usually < 10 mm in diameter.
- Micro: Granular cell tumour is an unencapsulated tumour composed of large polygonal cells with abundant eosinophilic granular cytoplasm and small round nuclei in the subepithelial tissue.
- Ancillary: The tumour cells are immunoreactive for S100, CD57, SOX10, inhibin, and calretinin.
Reference Gallery:
Granular cell tumour. The granular cells are immunoreactive for S100.
Granular cell tumour. Sheets of large polygonal cells intermingled with skeletal muscle fibres. The cells demonstrate abundant granular cytoplasm and small round nuclei either eccentrically or centrally located.
Granular cell tumour. Dramatic pseudoepitheliomatous hyperplasia of the overlying mucosa should not be erroneously interpreted as squamous cell carcinoma, and the unencapsulated mass of granular cells immediately beneath the epithelium should not be overlooked.

Q: Microscopically, a Granular Cell Tumor typically consists of unencapsulated sheets of large polygonal cells with small, round nuclei and abundant eosinophilic [...] cytoplasm.
Granular cell tumour. Sheets of large polygonal cells intermingled with skeletal muscle fibres. The cells demonstrate abundant granular cytoplasm and small round nuclei either eccentrically or centrally located.
A: granular
Back Extra: Granular Cell Tumor
- Clinical: Patients with granular cell tumour present with a non-tender, slowly enlarging, sessile mucosal to yellowish-coloured submucosal mass, usually < 10 mm in diameter.
- Micro: Granular cell tumour is an unencapsulated tumour composed of large polygonal cells with abundant eosinophilic granular cytoplasm and small round nuclei in the subepithelial tissue.
- Ancillary: The tumour cells are immunoreactive for S100, CD57, SOX10, inhibin, and calretinin.
Reference Gallery:
Granular cell tumour. The granular cells are immunoreactive for S100.
Granular cell tumour. Sheets of large polygonal cells intermingled with skeletal muscle fibres. The cells demonstrate abundant granular cytoplasm and small round nuclei either eccentrically or centrally located.
Granular cell tumour. Dramatic pseudoepitheliomatous hyperplasia of the overlying mucosa should not be erroneously interpreted as squamous cell carcinoma, and the unencapsulated mass of granular cells immediately beneath the epithelium should not be overlooked.

Q: Immunohistochemically, the neoplastic cells of a Granular Cell Tumor strongly express neural crest markers, most notably SOX10 and [...].
Granular cell tumour. The granular cells are immunoreactive for S100.
A: S100
Back Extra: Granular Cell Tumor
- Clinical: Patients with granular cell tumour present with a non-tender, slowly enlarging, sessile mucosal to yellowish-coloured submucosal mass, usually < 10 mm in diameter.
- Micro: Granular cell tumour is an unencapsulated tumour composed of large polygonal cells with abundant eosinophilic granular cytoplasm and small round nuclei in the subepithelial tissue.
- Ancillary: The tumour cells are immunoreactive for S100, CD57, SOX10, inhibin, and calretinin.
Reference Gallery:
Granular cell tumour. The granular cells are immunoreactive for S100.
Granular cell tumour. Sheets of large polygonal cells intermingled with skeletal muscle fibres. The cells demonstrate abundant granular cytoplasm and small round nuclei either eccentrically or centrally located.
Granular cell tumour. Dramatic pseudoepitheliomatous hyperplasia of the overlying mucosa should not be erroneously interpreted as squamous cell carcinoma, and the unencapsulated mass of granular cells immediately beneath the epithelium should not be overlooked.

Q: A rapidly enlarging, bluish-black mass in the upper alveolus of a 3- to 6-month-old infant is the classic clinical and gross presentation for [...].
Melanotic neuroectodermal tumour of infancy. This CT image shows a large jaw mass expanding into the soft tissues (arrow).
Melanotic neuroectodermal tumour of infancy. A tooth is incorporated into the tumour mass. Note the blue-black pigmentation.
A: melanotic neuroectodermal tumor of infancy
Back Extra: Melanotic Neuroectodermal Tumour of Infancy
- Clinical: Melanotic neuroectodermal tumour of infancy typically presents as a rapidly enlarging, bluish-black mass in the upper alveolus of infants aged 3-6 months, causing facial deformity and feeding disruption.
- Micro: Tumour cells are arranged in alveolar nests, cords, and trabeculae, with melanotic epithelial cells surrounding small neuroblast-like cells and forming tubuloglandular structures.
- Ancillary: Both small and large tumour cells express vimentin and synaptophysin, while large cells coexpress pancytokeratin, HMB45, and melan-A, confirming dual epithelial and melanocytic features.
Reference Gallery:
Melanotic neuroectodermal tumour of infancy. Aggregates of tumour cells separated by fibrous stroma. There are small blue cells, with larger epithelial cells at the periphery, some of which contain melanin pigment.
Melanotic neuroectodermal tumour of infancy. High-power view of the small neuroblast-like cells with hyperchromatic nuclei and scant cytoplasm associated with larger epithelial cells with vesicular nuclei and cytoplasmic pigment.
Melanotic neuroectodermal tumour of infancy. This CT image shows a large jaw mass expanding into the soft tissues (arrow).
Melanotic neuroectodermal tumour of infancy. A tooth is incorporated into the tumour mass. Note the blue-black pigmentation.

Q: Histologically, melanotic neuroectodermal tumor of infancy features alveolar nests composed of larger, melanin-containing epithelial cells at the periphery that surround a central population of [...].
Melanotic neuroectodermal tumour of infancy. Aggregates of tumour cells separated by fibrous stroma. There are small blue cells, with larger epithelial cells at the periphery, some of which contain melanin pigment.
Melanotic neuroectodermal tumour of infancy. High-power view of the small neuroblast-like cells with hyperchromatic nuclei and scant cytoplasm associated with larger epithelial cells with vesicular nuclei and cytoplasmic pigment.
A: small neuroblast-like cells
Back Extra: Melanotic Neuroectodermal Tumour of Infancy
- Clinical: Melanotic neuroectodermal tumour of infancy typically presents as a rapidly enlarging, bluish-black mass in the upper alveolus of infants aged 3-6 months, causing facial deformity and feeding disruption.
- Micro: Tumour cells are arranged in alveolar nests, cords, and trabeculae, with melanotic epithelial cells surrounding small neuroblast-like cells and forming tubuloglandular structures.
- Ancillary: Both small and large tumour cells express vimentin and synaptophysin, while large cells coexpress pancytokeratin, HMB45, and melan-A, confirming dual epithelial and melanocytic features.
Reference Gallery:
Melanotic neuroectodermal tumour of infancy. Aggregates of tumour cells separated by fibrous stroma. There are small blue cells, with larger epithelial cells at the periphery, some of which contain melanin pigment.
Melanotic neuroectodermal tumour of infancy. High-power view of the small neuroblast-like cells with hyperchromatic nuclei and scant cytoplasm associated with larger epithelial cells with vesicular nuclei and cytoplasmic pigment.
Melanotic neuroectodermal tumour of infancy. This CT image shows a large jaw mass expanding into the soft tissues (arrow).
Melanotic neuroectodermal tumour of infancy. A tooth is incorporated into the tumour mass. Note the blue-black pigmentation.

Q: Histologically, a Hamartomatous Polyp of the tonsil is characterized by an admixture of normal lymphoid tissue, fibrous stroma, and numerous dilated [...].
Polypoid lymphangioma. High-power image shows numerous small to medium-sized dilated vascular channels.
Lymphangiectatic fibrous polyp – hamartoma. Polypoid tumour from the palatine tonsil, with fibrous stroma and dilated vasculature intermixed with normal lymphoid stroma.
A: vascular channels
Back Extra: Hamartomatous Polyp
- Clinical: Patients with hamartomatous polyps may present with symptoms such as dysphagia, sore throat, globus, or obstructive symptoms.
- Micro: The microscopic appearance of a hamartomatous polyp includes numerous small to medium-sized dilated vascular channels, lymphoid tissue, and fibrous stroma.
- Ancillary: Ancillary studies are not typically required for the diagnosis of hamartomatous polyps.
Reference Gallery:
Lymphangiectatic fibrous polyp. Low-power image shows the lymphoid and fibrous component.
Polypoid lymphangioma. Low-power image shows the lymphoid and dilated vascular channels.
Polypoid lymphangioma. High-power image shows numerous small to medium-sized dilated vascular channels.
Lymphangiectatic fibrous polyp – hamartoma. Polypoid tumour from the palatine tonsil, with fibrous stroma and dilated vasculature intermixed with normal lymphoid stroma.
Lymphangiectatic fibrous polyp – hamartoma. Polypoid tumour from the palatine tonsil, with fibrous stroma and dilated vasculature intermixed with normal lymphoid stroma.

Q: A [...] of the upper aerodigestive tract may present with globus sensation and is characterized microscopically by a benign polypoid architecture containing normal lymphoid tissue, fibrous stroma, and lymphangiectatic spaces.
Lymphangiectatic fibrous polyp. Low-power image shows the lymphoid and fibrous component.
Polypoid lymphangioma. Low-power image shows the lymphoid and dilated vascular channels.
Lymphangiectatic fibrous polyp – hamartoma. Polypoid tumour from the palatine tonsil, with fibrous stroma and dilated vasculature intermixed with normal lymphoid stroma.
A: Hamartomatous Polyp
Back Extra: Hamartomatous Polyp
- Clinical: Patients with hamartomatous polyps may present with symptoms such as dysphagia, sore throat, globus, or obstructive symptoms.
- Micro: The microscopic appearance of a hamartomatous polyp includes numerous small to medium-sized dilated vascular channels, lymphoid tissue, and fibrous stroma.
- Ancillary: Ancillary studies are not typically required for the diagnosis of hamartomatous polyps.
Reference Gallery:
Lymphangiectatic fibrous polyp. Low-power image shows the lymphoid and fibrous component.
Polypoid lymphangioma. Low-power image shows the lymphoid and dilated vascular channels.
Polypoid lymphangioma. High-power image shows numerous small to medium-sized dilated vascular channels.
Lymphangiectatic fibrous polyp – hamartoma. Polypoid tumour from the palatine tonsil, with fibrous stroma and dilated vasculature intermixed with normal lymphoid stroma.
Lymphangiectatic fibrous polyp – hamartoma. Polypoid tumour from the palatine tonsil, with fibrous stroma and dilated vasculature intermixed with normal lymphoid stroma.

Q: The classic histologic appearance of Squamous Cell Carcinoma, HPV-associated features nests of [...] tumor cells with high N:C ratios, round to spindled nuclei, and a syncytial cytoplasm, often embedded in a lymphoid stroma.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype. Nests of cells with round to spindled, hyperchromatic nuclei, with abundant mitosis and apoptosis.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype. This non-keratinizing HPV-associated squamous cell carcinoma has large nests with smooth edges in a lymphoid stroma and with tumour cells with high N:C ratios and round to oval nuclei.
A: non-keratinizing
Q: Squamous Cell Carcinoma, HPV-associated
- Clinical: Patients with [...] oropharyngeal squamous cell carcinoma often present with painless cervical lymphadenopathy and small primary tumours that have metastasized to the upper and middle jugular chain lymph nodes.
- Micro: The histology of [...] oropharyngeal squamous cell carcinoma is characterized by non-keratinizing tumour cells with high N:C ratios, round to spindled nuclei, and syncytial cytoplasm.
- Ancillary: [...] nuclear and cytoplasmic p16 immunostaining is a reliable surrogate marker for high-risk HPV in oropharyngeal squamous cell carcinoma.
Reference Gallery:
Squamous cell carcinoma, HPV-associated. Oropharyngeal. Extensive surface growth mimicking an in situ process.
Squamous cell carcinoma, HPV-associated. Basaloid subtype. HPV detection (inset: DNA in situ hybridization) is needed to distinguish these tumours from the more aggressive basaloid variant of HPV-independent squamous cell carcinoma.
Squamous cell carcinoma, HPV-associated. Lymphoepithelial subtype. The tumour shows lymphoepithelial features including syncytial cytoplasm, vesicular nuclei with prominent central nucleoli, and an associated lymphoplasmacytic infiltrate.
Oropharyngeal carcinoma, HPV-associated. Adenosquamous subtype. HPV-associated oropharyngeal carcinoma exhibiting a non-keratinizing squamous cell component and a glandular component.
Squamous cell carcinoma, HPV-associated. High-risk HPV RNA in situ hybridization is positive in this HPV-associated carcinoma showing punctate, granular nuclear and cytoplasmic staining.
Squamous cell carcinoma, HPV-associated. A tumour showing strong and diffuse nuclear and cytoplasmic p16 staining.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype. Nests of cells with round to spindled, hyperchromatic nuclei, with abundant mitosis and apoptosis.
Squamous cell carcinoma, HPV-associated. Ciliated adenosquamous subtype. Rare HPV-associated carcinomas can have glands with cilia, seen here with rounded, smooth lumina and cells with terminal bar formation and prominent cilia.
Squamous cell carcinoma, HPV-associated. Example with nuclear anaplasia. Some HPV-associated squamous cell carcinomas show areas of tumour cell multinucleation and extreme nuclear pleomorphism, although this is not of clear prognostic significance.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype with maturation. Some HPV-associated squamous cell carcinomas have both non-keratinizing and keratinizing areas, which frequently show an unusual pattern of reverse maturation, where the keratinizing areas are peripheral with artefactual clefting.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype. This non-keratinizing HPV-associated squamous cell carcinoma has large nests with smooth edges in a lymphoid stroma and with tumour cells with high N:C ratios and round to oval nuclei.
Squamous cell carcinoma, HPV-associated. Estimated age-standardized incidence rates (ASRs, World Standard Population), per 100,000 person-years, of oropharyngeal squamous cell carcinoma in 2020 among both sexes (all ages).
A: HPV-associated; HPV-associated; Diffuse and strong

Q: In Squamous Cell Carcinoma, HPV-associated, a highly reliable surrogate immunohistochemical marker for high-risk viral infection is [...] nuclear and cytoplasmic p16 staining.
Squamous cell carcinoma, HPV-associated. A tumour showing strong and diffuse nuclear and cytoplasmic p16 staining.
A: diffuse and strong
Q: Squamous Cell Carcinoma, HPV-associated
- Clinical: Patients with [...] oropharyngeal squamous cell carcinoma often present with painless cervical lymphadenopathy and small primary tumours that have metastasized to the upper and middle jugular chain lymph nodes.
- Micro: The histology of [...] oropharyngeal squamous cell carcinoma is characterized by non-keratinizing tumour cells with high N:C ratios, round to spindled nuclei, and syncytial cytoplasm.
- Ancillary: [...] nuclear and cytoplasmic p16 immunostaining is a reliable surrogate marker for high-risk HPV in oropharyngeal squamous cell carcinoma.
Reference Gallery:
Squamous cell carcinoma, HPV-associated. Oropharyngeal. Extensive surface growth mimicking an in situ process.
Squamous cell carcinoma, HPV-associated. Basaloid subtype. HPV detection (inset: DNA in situ hybridization) is needed to distinguish these tumours from the more aggressive basaloid variant of HPV-independent squamous cell carcinoma.
Squamous cell carcinoma, HPV-associated. Lymphoepithelial subtype. The tumour shows lymphoepithelial features including syncytial cytoplasm, vesicular nuclei with prominent central nucleoli, and an associated lymphoplasmacytic infiltrate.
Oropharyngeal carcinoma, HPV-associated. Adenosquamous subtype. HPV-associated oropharyngeal carcinoma exhibiting a non-keratinizing squamous cell component and a glandular component.
Squamous cell carcinoma, HPV-associated. High-risk HPV RNA in situ hybridization is positive in this HPV-associated carcinoma showing punctate, granular nuclear and cytoplasmic staining.
Squamous cell carcinoma, HPV-associated. A tumour showing strong and diffuse nuclear and cytoplasmic p16 staining.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype. Nests of cells with round to spindled, hyperchromatic nuclei, with abundant mitosis and apoptosis.
Squamous cell carcinoma, HPV-associated. Ciliated adenosquamous subtype. Rare HPV-associated carcinomas can have glands with cilia, seen here with rounded, smooth lumina and cells with terminal bar formation and prominent cilia.
Squamous cell carcinoma, HPV-associated. Example with nuclear anaplasia. Some HPV-associated squamous cell carcinomas show areas of tumour cell multinucleation and extreme nuclear pleomorphism, although this is not of clear prognostic significance.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype with maturation. Some HPV-associated squamous cell carcinomas have both non-keratinizing and keratinizing areas, which frequently show an unusual pattern of reverse maturation, where the keratinizing areas are peripheral with artefactual clefting.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype. This non-keratinizing HPV-associated squamous cell carcinoma has large nests with smooth edges in a lymphoid stroma and with tumour cells with high N:C ratios and round to oval nuclei.
Squamous cell carcinoma, HPV-associated. Estimated age-standardized incidence rates (ASRs, World Standard Population), per 100,000 person-years, of oropharyngeal squamous cell carcinoma in 2020 among both sexes (all ages).
A: HPV-associated; HPV-associated; Diffuse and strong

Q: To definitively distinguish basaloid variants of Squamous Cell Carcinoma, HPV-associated from aggressive HPV-independent tumors, definitive detection of the virus via [...] is required, which typically shows punctate, granular staining.
Squamous cell carcinoma, HPV-associated. Basaloid subtype. HPV detection (inset: DNA in situ hybridization) is needed to distinguish these tumours from the more aggressive basaloid variant of HPV-independent squamous cell carcinoma.
Squamous cell carcinoma, HPV-associated. High-risk HPV RNA in situ hybridization is positive in this HPV-associated carcinoma showing punctate, granular nuclear and cytoplasmic staining.
A: in situ hybridization (ISH)
Q: Squamous Cell Carcinoma, HPV-associated
- Clinical: Patients with [...] oropharyngeal squamous cell carcinoma often present with painless cervical lymphadenopathy and small primary tumours that have metastasized to the upper and middle jugular chain lymph nodes.
- Micro: The histology of [...] oropharyngeal squamous cell carcinoma is characterized by non-keratinizing tumour cells with high N:C ratios, round to spindled nuclei, and syncytial cytoplasm.
- Ancillary: [...] nuclear and cytoplasmic p16 immunostaining is a reliable surrogate marker for high-risk HPV in oropharyngeal squamous cell carcinoma.
Reference Gallery:
Squamous cell carcinoma, HPV-associated. Oropharyngeal. Extensive surface growth mimicking an in situ process.
Squamous cell carcinoma, HPV-associated. Basaloid subtype. HPV detection (inset: DNA in situ hybridization) is needed to distinguish these tumours from the more aggressive basaloid variant of HPV-independent squamous cell carcinoma.
Squamous cell carcinoma, HPV-associated. Lymphoepithelial subtype. The tumour shows lymphoepithelial features including syncytial cytoplasm, vesicular nuclei with prominent central nucleoli, and an associated lymphoplasmacytic infiltrate.
Oropharyngeal carcinoma, HPV-associated. Adenosquamous subtype. HPV-associated oropharyngeal carcinoma exhibiting a non-keratinizing squamous cell component and a glandular component.
Squamous cell carcinoma, HPV-associated. High-risk HPV RNA in situ hybridization is positive in this HPV-associated carcinoma showing punctate, granular nuclear and cytoplasmic staining.
Squamous cell carcinoma, HPV-associated. A tumour showing strong and diffuse nuclear and cytoplasmic p16 staining.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype. Nests of cells with round to spindled, hyperchromatic nuclei, with abundant mitosis and apoptosis.
Squamous cell carcinoma, HPV-associated. Ciliated adenosquamous subtype. Rare HPV-associated carcinomas can have glands with cilia, seen here with rounded, smooth lumina and cells with terminal bar formation and prominent cilia.
Squamous cell carcinoma, HPV-associated. Example with nuclear anaplasia. Some HPV-associated squamous cell carcinomas show areas of tumour cell multinucleation and extreme nuclear pleomorphism, although this is not of clear prognostic significance.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype with maturation. Some HPV-associated squamous cell carcinomas have both non-keratinizing and keratinizing areas, which frequently show an unusual pattern of reverse maturation, where the keratinizing areas are peripheral with artefactual clefting.
Squamous cell carcinoma, HPV-associated. Non-keratinizing subtype. This non-keratinizing HPV-associated squamous cell carcinoma has large nests with smooth edges in a lymphoid stroma and with tumour cells with high N:C ratios and round to oval nuclei.
Squamous cell carcinoma, HPV-associated. Estimated age-standardized incidence rates (ASRs, World Standard Population), per 100,000 person-years, of oropharyngeal squamous cell carcinoma in 2020 among both sexes (all ages).
A: HPV-associated; HPV-associated; Diffuse and strong

Q: Microscopically, the keratinizing subtype of Squamous Cell Carcinoma, HPV-independent typically demonstrates infiltrative, angulated tumor nests associated with a pronounced [...] and the formation of keratin pearls.
Squamous cell carcinoma, HPV-independent. Keratinizing subtype. The tumour shows irregular, angulated nests of cells with dense, eosinophilic cytoplasm with rare keratin pearls and associated desmoplastic stromal reaction.
A: stromal desmoplasia
Back Extra: Squamous Cell Carcinoma, HPV-independent
- Clinical: Patients typically present with symptoms such as pain/sore throat, dysphagia, and/or a neck mass.
- Micro: The tumour nests are infiltrative and angulated, often surrounded by prominent stromal desmoplasia, with keratinization and intercellular bridges present.
- Ancillary: Transcriptionally active HPV is absent, and p16 is typically not overexpressed, with a nuclear and cytoplasmic cut-off point of 70% used as a negative surrogate for high-risk HPV.
Reference Gallery:
Squamous cell carcinoma, HPV-independent. Carcinomas usually arise from the surface mucosa but may extend into tonsillar lymphoid tissue.
Squamous cell carcinoma, HPV-independent. Keratinizing subtype. The tumour shows irregular, angulated nests of cells with dense, eosinophilic cytoplasm with rare keratin pearls and associated desmoplastic stromal reaction.
Squamous cell carcinoma, HPV-independent. Keratinizing subtype, p16-negative. Immunohistochemistry for p16 shows that the tumour cells have only patchy, moderate-intensity reactivity in much less than 70% of tumour cells, a negative result (as a surrogate of high-risk HPV).

Q: To confirm the diagnosis of Squamous Cell Carcinoma, HPV-independent, immunohistochemistry for p16 will be [...], demonstrating only patchy or no reactivity (using a cut-off of less than 70% of tumor cells).
Squamous cell carcinoma, HPV-independent. Keratinizing subtype, p16-negative. Immunohistochemistry for p16 shows that the tumour cells have only patchy, moderate-intensity reactivity in much less than 70% of tumour cells, a negative result (as a surrogate of high-risk HPV).
A: negative
Back Extra: Squamous Cell Carcinoma, HPV-independent
- Clinical: Patients typically present with symptoms such as pain/sore throat, dysphagia, and/or a neck mass.
- Micro: The tumour nests are infiltrative and angulated, often surrounded by prominent stromal desmoplasia, with keratinization and intercellular bridges present.
- Ancillary: Transcriptionally active HPV is absent, and p16 is typically not overexpressed, with a nuclear and cytoplasmic cut-off point of 70% used as a negative surrogate for high-risk HPV.
Reference Gallery:
Squamous cell carcinoma, HPV-independent. Carcinomas usually arise from the surface mucosa but may extend into tonsillar lymphoid tissue.
Squamous cell carcinoma, HPV-independent. Keratinizing subtype. The tumour shows irregular, angulated nests of cells with dense, eosinophilic cytoplasm with rare keratin pearls and associated desmoplastic stromal reaction.
Squamous cell carcinoma, HPV-independent. Keratinizing subtype, p16-negative. Immunohistochemistry for p16 shows that the tumour cells have only patchy, moderate-intensity reactivity in much less than 70% of tumour cells, a negative result (as a surrogate of high-risk HPV).

Q: Histologically, Basal Cell Adenoma is characterized by prominent [...] of dark basaloid cells around paler luminal cells and ducts.
Basal cell adenoma. Tubulotrabecular pattern. Note the peripheral palisading.
Basal cell adenoma. Cribriform pattern. Note the peripheral palisading.
A: peripheral palisading
Back Extra: Basal Cell Adenoma
- Clinical: Basal cell adenomas present as well-defined, mobile, solitary masses, more common in the sixth and seventh decades with a slight female predilection.
- Micro: The tumour shows peripheral palisading of dark cells with luminal paler cells and ducts, and stroma of variable amount and collagenous density.
- Ancillary: Coexpression of nuclear β-catenin and LEF1 is detected in basal cell adenomas, and CTNNB1 alterations are often present, especially in tubulotrabecular BCA.
Reference Gallery:
Basal cell adenoma. Most tumours are encapsulated.
Basal cell adenoma. Tubulotrabecular pattern. Note the peripheral palisading.
Basal cell adenoma. Cribriform pattern. Note the peripheral palisading.
Basal cell adenoma. Trabecular pattern with a myoepithelial-derived stromal component. Note the peripheral palisading.
Basal cell adenoma. Membranous pattern. Note the peripheral palisading.
Basal cell adenoma. These tumours often show nuclear localization of β-catenin, typically in the peripheral cell layer.
Basal cell adenoma. LEF1 shows strong nuclear staining of peripheral cell layers.
Basal cell adenoma. Tumour cells are monomorphic with scant cytoplasm. Here, they are arranged in arborizing fragments with scant, interdigitating hyaline stroma. Scattered naked nuclei are noted. (FNAC, Giemsa.)
Basal cell adenoma. Nuclei are vesicular and are accentuated at the periphery of cell fragments. (FNAC, Pap.)
Basal cell adenoma. Grossly, basal cell adenomas are well circumscribed and show a homogeneous grey-tan cut surface.
Basal cell adenoma. Axial CT demonstrates a smooth, homogeneous ovoid mass within the parotid gland. No destructive growth is noted.
Basal cell adenoma. Coronal CT demonstrates a smooth, homogeneous ovoid mass within the parotid gland. No destructive growth is noted.

Q: A defining immunohistochemical feature of Basal Cell Adenoma (often driven by CTNNB1 alterations) is the nuclear co-expression of LEF1 and [...], typically accentuating the outer cell layer.
Basal cell adenoma. These tumours often show nuclear localization of β-catenin, typically in the peripheral cell layer.
Basal cell adenoma. LEF1 shows strong nuclear staining of peripheral cell layers.
A: beta-catenin
Back Extra: Basal Cell Adenoma
- Clinical: Basal cell adenomas present as well-defined, mobile, solitary masses, more common in the sixth and seventh decades with a slight female predilection.
- Micro: The tumour shows peripheral palisading of dark cells with luminal paler cells and ducts, and stroma of variable amount and collagenous density.
- Ancillary: Coexpression of nuclear β-catenin and LEF1 is detected in basal cell adenomas, and CTNNB1 alterations are often present, especially in tubulotrabecular BCA.
Reference Gallery:
Basal cell adenoma. Most tumours are encapsulated.
Basal cell adenoma. Tubulotrabecular pattern. Note the peripheral palisading.
Basal cell adenoma. Cribriform pattern. Note the peripheral palisading.
Basal cell adenoma. Trabecular pattern with a myoepithelial-derived stromal component. Note the peripheral palisading.
Basal cell adenoma. Membranous pattern. Note the peripheral palisading.
Basal cell adenoma. These tumours often show nuclear localization of β-catenin, typically in the peripheral cell layer.
Basal cell adenoma. LEF1 shows strong nuclear staining of peripheral cell layers.
Basal cell adenoma. Tumour cells are monomorphic with scant cytoplasm. Here, they are arranged in arborizing fragments with scant, interdigitating hyaline stroma. Scattered naked nuclei are noted. (FNAC, Giemsa.)
Basal cell adenoma. Nuclei are vesicular and are accentuated at the periphery of cell fragments. (FNAC, Pap.)
Basal cell adenoma. Grossly, basal cell adenomas are well circumscribed and show a homogeneous grey-tan cut surface.
Basal cell adenoma. Axial CT demonstrates a smooth, homogeneous ovoid mass within the parotid gland. No destructive growth is noted.
Basal cell adenoma. Coronal CT demonstrates a smooth, homogeneous ovoid mass within the parotid gland. No destructive growth is noted.

Q: Grossly and microscopically, Basal Cell Adenoma typically presents as a smooth, well-circumscribed, and distinctly [...] mass with a homogeneous gray-tan appearance.
Basal cell adenoma. Most tumours are encapsulated.
Basal cell adenoma. Grossly, basal cell adenomas are well circumscribed and show a homogeneous grey-tan cut surface.
A: encapsulated
Back Extra: Basal Cell Adenoma
- Clinical: Basal cell adenomas present as well-defined, mobile, solitary masses, more common in the sixth and seventh decades with a slight female predilection.
- Micro: The tumour shows peripheral palisading of dark cells with luminal paler cells and ducts, and stroma of variable amount and collagenous density.
- Ancillary: Coexpression of nuclear β-catenin and LEF1 is detected in basal cell adenomas, and CTNNB1 alterations are often present, especially in tubulotrabecular BCA.
Reference Gallery:
Basal cell adenoma. Most tumours are encapsulated.
Basal cell adenoma. Tubulotrabecular pattern. Note the peripheral palisading.
Basal cell adenoma. Cribriform pattern. Note the peripheral palisading.
Basal cell adenoma. Trabecular pattern with a myoepithelial-derived stromal component. Note the peripheral palisading.
Basal cell adenoma. Membranous pattern. Note the peripheral palisading.
Basal cell adenoma. These tumours often show nuclear localization of β-catenin, typically in the peripheral cell layer.
Basal cell adenoma. LEF1 shows strong nuclear staining of peripheral cell layers.
Basal cell adenoma. Tumour cells are monomorphic with scant cytoplasm. Here, they are arranged in arborizing fragments with scant, interdigitating hyaline stroma. Scattered naked nuclei are noted. (FNAC, Giemsa.)
Basal cell adenoma. Nuclei are vesicular and are accentuated at the periphery of cell fragments. (FNAC, Pap.)
Basal cell adenoma. Grossly, basal cell adenomas are well circumscribed and show a homogeneous grey-tan cut surface.
Basal cell adenoma. Axial CT demonstrates a smooth, homogeneous ovoid mass within the parotid gland. No destructive growth is noted.
Basal cell adenoma. Coronal CT demonstrates a smooth, homogeneous ovoid mass within the parotid gland. No destructive growth is noted.

Q: Clinically, patients with Canalicular Adenoma typically present with a slowly growing, painless, non-ulcerated mass most commonly located in the [...].
Canalicular adenoma. A clinical image showing an upper-lip subepithelial nodule, characteristic of canalicular adenoma.
A: upper lip
Q: Canalicular Adenoma
- Clinical: Patients with [...] present with a slowly growing, mobile, painless, non-ulcerated mass, commonly in the upper lip.
- Micro: The epithelial cells in [...] are arranged in anastomosing cords, canalcules, and ribbons, often forming a characteristic 'beading' pattern.
- Ancillary: Immunohistochemically, [...] cells are positive for S100 and GFAP (peripheral), but negative for DOG1, desmin, and actins.
Reference Gallery:
Salivary canalicular adenoma. Multifocality identified by identical tumour foci that are separate from the main tumour mass.
Salivary canalicular adenoma. Low-power view demonstrates the interlacing canals and ribbons of neoplastic cuboidal-columnar cells separated by a loose, oedematous stroma.
Salivary canalicular adenoma. This cellular tumour demonstrates a tight, glandular, ribbon-like architecture composed of a syncytium of short columnar epithelial cells.
Salivary canalicular adenoma. Adjacent ribbons of cells come together and form a knot (beading), a feature quite characteristic of canalicular adenoma.
Salivary canalicular adenoma. The canals contain squamoid morules, histiocytes, and calcifications.
Salivary canalicular adenoma. All of the neoplastic cells show a strong and diffuse nuclear and cytoplasmic reaction for S100.
Salivary canalicular adenoma. There is a curious peripheral GFAP immunoreactivity, while the central tumour cells are non-reactive.
Canalicular adenoma. A clinical image showing an upper-lip subepithelial nodule, characteristic of canalicular adenoma.
A: canalicular adenoma; canalicular adenoma; canalicular adenoma

Q: Microscopically, Canalicular Adenoma is characterized by columnar epithelial cells in a loose, edematous stroma, arranged in anastomosing ribbons that often come together to form tight knots, known as a characteristic [...] pattern.
Salivary canalicular adenoma. Low-power view demonstrates the interlacing canals and ribbons of neoplastic cuboidal-columnar cells separated by a loose, oedematous stroma.
Salivary canalicular adenoma. Adjacent ribbons of cells come together and form a knot (beading), a feature quite characteristic of canalicular adenoma.
A: "beading"
Q: Canalicular Adenoma
- Clinical: Patients with [...] present with a slowly growing, mobile, painless, non-ulcerated mass, commonly in the upper lip.
- Micro: The epithelial cells in [...] are arranged in anastomosing cords, canalcules, and ribbons, often forming a characteristic 'beading' pattern.
- Ancillary: Immunohistochemically, [...] cells are positive for S100 and GFAP (peripheral), but negative for DOG1, desmin, and actins.
Reference Gallery:
Salivary canalicular adenoma. Multifocality identified by identical tumour foci that are separate from the main tumour mass.
Salivary canalicular adenoma. Low-power view demonstrates the interlacing canals and ribbons of neoplastic cuboidal-columnar cells separated by a loose, oedematous stroma.
Salivary canalicular adenoma. This cellular tumour demonstrates a tight, glandular, ribbon-like architecture composed of a syncytium of short columnar epithelial cells.
Salivary canalicular adenoma. Adjacent ribbons of cells come together and form a knot (beading), a feature quite characteristic of canalicular adenoma.
Salivary canalicular adenoma. The canals contain squamoid morules, histiocytes, and calcifications.
Salivary canalicular adenoma. All of the neoplastic cells show a strong and diffuse nuclear and cytoplasmic reaction for S100.
Salivary canalicular adenoma. There is a curious peripheral GFAP immunoreactivity, while the central tumour cells are non-reactive.
Canalicular adenoma. A clinical image showing an upper-lip subepithelial nodule, characteristic of canalicular adenoma.
A: canalicular adenoma; canalicular adenoma; canalicular adenoma

Q: Immunohistochemically, Canalicular Adenoma is typically diffusely positive for S100 and shows a curious peripheral pattern of immunoreactivity for [...].
Salivary canalicular adenoma. All of the neoplastic cells show a strong and diffuse nuclear and cytoplasmic reaction for S100.
Salivary canalicular adenoma. There is a curious peripheral GFAP immunoreactivity, while the central tumour cells are non-reactive.
A: GFAP
Q: Canalicular Adenoma
- Clinical: Patients with [...] present with a slowly growing, mobile, painless, non-ulcerated mass, commonly in the upper lip.
- Micro: The epithelial cells in [...] are arranged in anastomosing cords, canalcules, and ribbons, often forming a characteristic 'beading' pattern.
- Ancillary: Immunohistochemically, [...] cells are positive for S100 and GFAP (peripheral), but negative for DOG1, desmin, and actins.
Reference Gallery:
Salivary canalicular adenoma. Multifocality identified by identical tumour foci that are separate from the main tumour mass.
Salivary canalicular adenoma. Low-power view demonstrates the interlacing canals and ribbons of neoplastic cuboidal-columnar cells separated by a loose, oedematous stroma.
Salivary canalicular adenoma. This cellular tumour demonstrates a tight, glandular, ribbon-like architecture composed of a syncytium of short columnar epithelial cells.
Salivary canalicular adenoma. Adjacent ribbons of cells come together and form a knot (beading), a feature quite characteristic of canalicular adenoma.
Salivary canalicular adenoma. The canals contain squamoid morules, histiocytes, and calcifications.
Salivary canalicular adenoma. All of the neoplastic cells show a strong and diffuse nuclear and cytoplasmic reaction for S100.
Salivary canalicular adenoma. There is a curious peripheral GFAP immunoreactivity, while the central tumour cells are non-reactive.
Canalicular adenoma. A clinical image showing an upper-lip subepithelial nodule, characteristic of canalicular adenoma.
A: canalicular adenoma; canalicular adenoma; canalicular adenoma

Q: The oncocytic-papillary subtype of Cystadenoma of the salivary glands typically features a cystic lesion lined by an epithelium composed of [...] cells that frequently exhibit variable papillary configurations.
Cystadenoma of the salivary gland, oncocytic–papillary subtype. A unicystic lesion lined by oncocytic epithelium with a variable papillary configuration.
A: oncocytic
Back Extra: Cystadenoma of the salivary glands
- Clinical: Cystadenomas present as slowly growing, painless nodules or masses, more commonly affecting women in the fifth to seventh decade of life.
- Micro: Cystadenomas are well circumscribed, with cysts lined by an admixture of columnar, cuboidal, and oncocytic cells, and lack cytological atypia or invasive growth.
- Ancillary: The lining cells show a simple luminal phenotype (CK8/18+) supported by a p63+ basal cell layer, and testing can exclude other cystic tumour entities like secretory carcinoma (ETV6) and mucoepidermoid carcinoma (MAML2).
Reference Gallery:
Cystadenoma of the salivary gland. The cysts in this tumour are lined predominantly by apocrine cells.
Cystadenoma of the salivary gland, oncocytic–papillary subtype. A unicystic lesion lined by oncocytic epithelium with a variable papillary configuration.
Cystadenoma of the salivary gland, mucinous subtype. A multicystic tumour composed of large cysts lined by well-oriented mucinous cells with basal nuclei and focal papillae supported by a basal cell layer. No MAML2 fusion was detected.

Q: The mucinous subtype of Cystadenoma of the salivary glands can morphologically mimic mucoepidermoid carcinoma, but is molecularly differentiated by the absence of a [...] gene fusion.
Cystadenoma of the salivary gland, mucinous subtype. A multicystic tumour composed of large cysts lined by well-oriented mucinous cells with basal nuclei and focal papillae supported by a basal cell layer. No MAML2 fusion was detected.
A: MAML2
Back Extra: Cystadenoma of the salivary glands
- Clinical: Cystadenomas present as slowly growing, painless nodules or masses, more commonly affecting women in the fifth to seventh decade of life.
- Micro: Cystadenomas are well circumscribed, with cysts lined by an admixture of columnar, cuboidal, and oncocytic cells, and lack cytological atypia or invasive growth.
- Ancillary: The lining cells show a simple luminal phenotype (CK8/18+) supported by a p63+ basal cell layer, and testing can exclude other cystic tumour entities like secretory carcinoma (ETV6) and mucoepidermoid carcinoma (MAML2).
Reference Gallery:
Cystadenoma of the salivary gland. The cysts in this tumour are lined predominantly by apocrine cells.
Cystadenoma of the salivary gland, oncocytic–papillary subtype. A unicystic lesion lined by oncocytic epithelium with a variable papillary configuration.
Cystadenoma of the salivary gland, mucinous subtype. A multicystic tumour composed of large cysts lined by well-oriented mucinous cells with basal nuclei and focal papillae supported by a basal cell layer. No MAML2 fusion was detected.

Q: Morphologically, Cystadenoma of the salivary glands may present as well-circumscribed cysts lined predominantly by eosinophilic [...] cells, completely lacking cytological atypia or invasive growth.
Cystadenoma of the salivary gland. The cysts in this tumour are lined predominantly by apocrine cells.
A: apocrine
Back Extra: Cystadenoma of the salivary glands
- Clinical: Cystadenomas present as slowly growing, painless nodules or masses, more commonly affecting women in the fifth to seventh decade of life.
- Micro: Cystadenomas are well circumscribed, with cysts lined by an admixture of columnar, cuboidal, and oncocytic cells, and lack cytological atypia or invasive growth.
- Ancillary: The lining cells show a simple luminal phenotype (CK8/18+) supported by a p63+ basal cell layer, and testing can exclude other cystic tumour entities like secretory carcinoma (ETV6) and mucoepidermoid carcinoma (MAML2).
Reference Gallery:
Cystadenoma of the salivary gland. The cysts in this tumour are lined predominantly by apocrine cells.
Cystadenoma of the salivary gland, oncocytic–papillary subtype. A unicystic lesion lined by oncocytic epithelium with a variable papillary configuration.
Cystadenoma of the salivary gland, mucinous subtype. A multicystic tumour composed of large cysts lined by well-oriented mucinous cells with basal nuclei and focal papillae supported by a basal cell layer. No MAML2 fusion was detected.

Q: The intraductal variant of Ductal Papilloma typically presents microscopically as a unilocular cyst with [...] proliferations lined by bland cuboidal to columnar and mucoid cells.
Intraductal papilloma. A unilocular lesion with intracystic papillary proliferation.
Intraductal papilloma. Bland cuboidal to columnar tumour cells are admixed with some mucoid cells.
A: intracystic papillary
Back Extra: Ductal Papilloma
- Clinical: Ductal papillomas (DPs) present as slowly growing, painless submucosal lesions or polypoid intraoral lesions, affecting adults with no sex predilection.
- Micro: Intraductal papillomas are unicystic lesions with papillary projections lined by columnar cells, while inverted ductal papillomas are endophytic, unencapsulated tumours with well-defined borders.
- Ancillary: Immunohistochemistry is of little diagnostic value, and HPV DNA is rarely detected.
Reference Gallery:
Ductal papilloma, inverted. The tumour has well-defined borders and is characterized by endophytic growth.
Ductal papilloma, inverted. At higher magnification, the tumour is seen to be composed of squamoid cells and some mucous cells, with no atypia.
Intraductal papilloma. A unilocular lesion with intracystic papillary proliferation.
Intraductal papilloma. Bland cuboidal to columnar tumour cells are admixed with some mucoid cells.

Q: The inverted variant of Ductal Papilloma is characterized microscopically by a well-defined, unencapsulated tumor that exhibits an [...] growth pattern composed of bland squamoid and mucous cells.
Ductal papilloma, inverted. The tumour has well-defined borders and is characterized by endophytic growth.
Ductal papilloma, inverted. At higher magnification, the tumour is seen to be composed of squamoid cells and some mucous cells, with no atypia.
A: endophytic
Back Extra: Ductal Papilloma
- Clinical: Ductal papillomas (DPs) present as slowly growing, painless submucosal lesions or polypoid intraoral lesions, affecting adults with no sex predilection.
- Micro: Intraductal papillomas are unicystic lesions with papillary projections lined by columnar cells, while inverted ductal papillomas are endophytic, unencapsulated tumours with well-defined borders.
- Ancillary: Immunohistochemistry is of little diagnostic value, and HPV DNA is rarely detected.
Reference Gallery:
Ductal papilloma, inverted. The tumour has well-defined borders and is characterized by endophytic growth.
Ductal papilloma, inverted. At higher magnification, the tumour is seen to be composed of squamoid cells and some mucous cells, with no atypia.
Intraductal papilloma. A unilocular lesion with intracystic papillary proliferation.
Intraductal papilloma. Bland cuboidal to columnar tumour cells are admixed with some mucoid cells.

Q: The typical histological appearance of Intercalated Duct Adenoma and Hyperplasia is a nodular or multinodular proliferation of monotonous [...] that often contain delicate eosinophilic cytoplasmic granules.
Salivary intercalated duct adenoma. Low-power view demonstrates an irregular periphery, with multinodularity. The proliferation is a monotonous single-cell population, with acinar cells at the periphery.
Salivary intercalated duct adenoma. A monotonous proliferation of cuboidal cells arranged in an acinar configuration. Note the delicate eosinophilic cytoplasmic granules.
A: cuboidal ductal cells
Back Extra: Intercalated Duct Adenoma and Hyperplasia
- Clinical: Most cases of Intercalated Duct Adenoma and Hyperplasia are incidental, often identified concurrently with other salivary gland lesions, and have an M:F ratio of 2:3, occurring in middle age (mean age: 52 years).
- Micro: Intercalated duct lesions are characterized by a nodular or multinodular proliferation of cuboidal ductal cells with attenuated myoepithelial cells, and are subclassified into adenoma (well-circumscribed or encapsulated) and hyperplasia (blending with adjacent acini).
- Ancillary: Adenomas often harbor HRAS pathogenic variants, while hyperplasia frequently shows CTNNB1 mutations, though these molecular findings are not clinically relevant for diagnosis.
Reference Gallery:
Salivary intercalated duct adenoma. Low-power view demonstrates an irregular periphery, with multinodularity. The proliferation is a monotonous single-cell population, with acinar cells at the periphery.
Salivary intercalated duct adenoma. A monotonous proliferation of cuboidal cells arranged in an acinar configuration. Note the delicate eosinophilic cytoplasmic granules.
Salivary intercalated duct lesion. The separation of adenoma from hyperplasia is challenging, because sometimes there is a blending at the periphery with acinar cells (dark blue cytoplasmic granules), whereas the proliferation contains eosinophilic cytoplasmic granules.
Intercalated duct hyperplasia. Proliferation of small eosinophilic tubules with transition from acini.

Q: In Intercalated Duct Adenoma and Hyperplasia, the hyperplasia subtype is microscopically distinguished from the adenoma subtype by its tendency to [...] rather than forming a well-circumscribed or encapsulated mass.
Salivary intercalated duct lesion. The separation of adenoma from hyperplasia is challenging, because sometimes there is a blending at the periphery with acinar cells (dark blue cytoplasmic granules), whereas the proliferation contains eosinophilic cytoplasmic granules.
Intercalated duct hyperplasia. Proliferation of small eosinophilic tubules with transition from acini.
A: blend with adjacent acini
Back Extra: Intercalated Duct Adenoma and Hyperplasia
- Clinical: Most cases of Intercalated Duct Adenoma and Hyperplasia are incidental, often identified concurrently with other salivary gland lesions, and have an M:F ratio of 2:3, occurring in middle age (mean age: 52 years).
- Micro: Intercalated duct lesions are characterized by a nodular or multinodular proliferation of cuboidal ductal cells with attenuated myoepithelial cells, and are subclassified into adenoma (well-circumscribed or encapsulated) and hyperplasia (blending with adjacent acini).
- Ancillary: Adenomas often harbor HRAS pathogenic variants, while hyperplasia frequently shows CTNNB1 mutations, though these molecular findings are not clinically relevant for diagnosis.
Reference Gallery:
Salivary intercalated duct adenoma. Low-power view demonstrates an irregular periphery, with multinodularity. The proliferation is a monotonous single-cell population, with acinar cells at the periphery.
Salivary intercalated duct adenoma. A monotonous proliferation of cuboidal cells arranged in an acinar configuration. Note the delicate eosinophilic cytoplasmic granules.
Salivary intercalated duct lesion. The separation of adenoma from hyperplasia is challenging, because sometimes there is a blending at the periphery with acinar cells (dark blue cytoplasmic granules), whereas the proliferation contains eosinophilic cytoplasmic granules.
Intercalated duct hyperplasia. Proliferation of small eosinophilic tubules with transition from acini.

Q: A slowly growing parotid gland tumor that grossly displays multiple cystic formations filled with lamellar keratin-like material is characteristic of [...].
Keratocystoma. Cut surface of the parotid tumour, showing multiple cystic formations filled with keratin-like material.
A: Keratocystoma
Back Extra: Keratocystoma
- Clinical: Keratocystoma typically presents as a painless, slowly growing parotid gland mass in patients aged 8–49 years.
- Micro: The cyst wall of keratocystoma is lined by bland stratified squamous epithelium with parakeratotic cells, and the cystic spaces contain keratotic lamellae.
- Ancillary: Keratocystoma is characterized by RUNX2 rearrangements, often with IRF2BP2::RUNX2 fusion, and immunostains for S100, SMA, and calponin are negative.
Reference Gallery:
Keratocystoma. Cut surface of the parotid tumour, showing multiple cystic formations filled with keratin-like material.
Keratocystoma. Multiple cysts with focal bud-like epithelial outer protrusions and a few solid epithelial cell nests. The cystic spaces contain lamellar keratin material.
Keratocystoma. The cyst wall is lined by bland stratified squamous epithelium with keratinization through parakeratotic cells. Note the lack of a granular cell layer.

Q: Microscopically, the cyst walls of a Keratocystoma are lined by bland stratified squamous epithelium that exhibits [...] and notably lacks a granular cell layer.
Keratocystoma. Multiple cysts with focal bud-like epithelial outer protrusions and a few solid epithelial cell nests. The cystic spaces contain lamellar keratin material.
Keratocystoma. The cyst wall is lined by bland stratified squamous epithelium with keratinization through parakeratotic cells. Note the lack of a granular cell layer.
A: parakeratosis
Back Extra: Keratocystoma
- Clinical: Keratocystoma typically presents as a painless, slowly growing parotid gland mass in patients aged 8–49 years.
- Micro: The cyst wall of keratocystoma is lined by bland stratified squamous epithelium with parakeratotic cells, and the cystic spaces contain keratotic lamellae.
- Ancillary: Keratocystoma is characterized by RUNX2 rearrangements, often with IRF2BP2::RUNX2 fusion, and immunostains for S100, SMA, and calponin are negative.
Reference Gallery:
Keratocystoma. Cut surface of the parotid tumour, showing multiple cystic formations filled with keratin-like material.
Keratocystoma. Multiple cysts with focal bud-like epithelial outer protrusions and a few solid epithelial cell nests. The cystic spaces contain lamellar keratin material.
Keratocystoma. The cyst wall is lined by bland stratified squamous epithelium with keratinization through parakeratotic cells. Note the lack of a granular cell layer.

Q: Grossly, a parotid gland tumor presenting as a well-circumscribed mass with numerous cysts filled with yellow, greasy material is characteristic of the [...] variant of Lymphadenoma.
Sebaceous lymphadenoma. The cut surface of this parotid gland tumour shows numerous cysts filled with yellow, greasy sebaceous material.
A: sebaceous
Back Extra: Lymphadenoma
- Clinical: Lymphadenomas present as slowly growing, painless masses, most commonly in the parotid gland. They are rare, representing <0.5% of salivary gland adenomas, with a median patient age of 59 years.
- Micro: Sebaceous lymphadenomas are characterized by well-circumscribed lesions with numerous variably sized ducts, sebaceous differentiation, and a benign lymphoid background. Histiocytes and foreign body giant cells are often present due to sebum leakage.
- Ancillary: Sebocytes stain positive for p63, EMA, adipophilin, and perilipin. Basal cells are positive for CK5/6 and p63, while luminal epithelial cells stain for CK7, CK18, and CK19. The Ki-67 index is typically <10%.
Reference Gallery:
Sebaceous lymphadenoma. The cut surface of this parotid gland tumour shows numerous cysts filled with yellow, greasy sebaceous material.
Lymphadenoma. Numerous cystic spaces and small ducts are noted, many showing microvesicular cytoplasm as would be expected in sebaceous differentiation.
Lymphadenoma. Sebaceous lymphadenoma. Small glands are lined by cuboidal cells, and numerous sebocytes are noted throughout, a finding seen in sebaceous lymphadenoma. Note the lymphoid stroma in the background.

Q: Microscopically, a salivary gland tumor characterized by cystic spaces and small ducts exhibiting sebaceous differentiation set within a dense, benign lymphoid stroma is diagnostic of the sebaceous variant of [...].
Lymphadenoma. Numerous cystic spaces and small ducts are noted, many showing microvesicular cytoplasm as would be expected in sebaceous differentiation.
Lymphadenoma. Sebaceous lymphadenoma. Small glands are lined by cuboidal cells, and numerous sebocytes are noted throughout, a finding seen in sebaceous lymphadenoma. Note the lymphoid stroma in the background.
A: Lymphadenoma
Back Extra: Lymphadenoma
- Clinical: Lymphadenomas present as slowly growing, painless masses, most commonly in the parotid gland. They are rare, representing <0.5% of salivary gland adenomas, with a median patient age of 59 years.
- Micro: Sebaceous lymphadenomas are characterized by well-circumscribed lesions with numerous variably sized ducts, sebaceous differentiation, and a benign lymphoid background. Histiocytes and foreign body giant cells are often present due to sebum leakage.
- Ancillary: Sebocytes stain positive for p63, EMA, adipophilin, and perilipin. Basal cells are positive for CK5/6 and p63, while luminal epithelial cells stain for CK7, CK18, and CK19. The Ki-67 index is typically <10%.
Reference Gallery:
Sebaceous lymphadenoma. The cut surface of this parotid gland tumour shows numerous cysts filled with yellow, greasy sebaceous material.
Lymphadenoma. Numerous cystic spaces and small ducts are noted, many showing microvesicular cytoplasm as would be expected in sebaceous differentiation.
Lymphadenoma. Sebaceous lymphadenoma. Small glands are lined by cuboidal cells, and numerous sebocytes are noted throughout, a finding seen in sebaceous lymphadenoma. Note the lymphoid stroma in the background.

Q: Microscopically, Salivary Gland Myoepithelioma is a well-circumscribed tumor composed of cells with variable morphology, typically showing spindled, clear, epithelioid, or [...] features.
Salivary gland myoepithelioma. Epithelioid and plasmacytoid myoepithelial cells.
A: plasmacytoid
Back Extra: Salivary Gland Myoepithelioma
- Clinical: Salivary Gland Myoepithelioma presents as a painless slow-growing mass, affects both sexes equally, and is most common in middle-aged individuals.
- Micro: The tumour is well-circumscribed and encapsulated, composed of myoepithelial cells with variable morphology (spindled, epithelioid, plasmacytoid, or clear).
- Ancillary: Positive for keratins, S100, SOX10, and myoepithelial markers like p63, calponin, and SMA; PLAG1 rearrangement may be detected.
Reference Gallery:
Salivary gland myoepithelioma. Epithelioid and plasmacytoid myoepithelial cells.
Salivary gland myoepithelioma. Well-circumscribed, non-invasive tumour surrounded by a capsule composed of spindle-shaped cells with myoepithelial differentiation.
Salivary gland myoepithelioma. Spindle cell with adipose metaplasia. The tumour is composed of spindled myoepithelial cells with adipose metaplasia.
Salivary gland myoepithelioma. The tumour is well circumscribed, encapsulated, and composed of myoepithelial cells.

Q: In Salivary Gland Myoepithelioma, the neoplastic spindled myoepithelial cells can occasionally undergo [...].
Salivary gland myoepithelioma. Spindle cell with adipose metaplasia. The tumour is composed of spindled myoepithelial cells with adipose metaplasia.
A: adipose metaplasia
Back Extra: Salivary Gland Myoepithelioma
- Clinical: Salivary Gland Myoepithelioma presents as a painless slow-growing mass, affects both sexes equally, and is most common in middle-aged individuals.
- Micro: The tumour is well-circumscribed and encapsulated, composed of myoepithelial cells with variable morphology (spindled, epithelioid, plasmacytoid, or clear).
- Ancillary: Positive for keratins, S100, SOX10, and myoepithelial markers like p63, calponin, and SMA; PLAG1 rearrangement may be detected.
Reference Gallery:
Salivary gland myoepithelioma. Epithelioid and plasmacytoid myoepithelial cells.
Salivary gland myoepithelioma. Well-circumscribed, non-invasive tumour surrounded by a capsule composed of spindle-shaped cells with myoepithelial differentiation.
Salivary gland myoepithelioma. Spindle cell with adipose metaplasia. The tumour is composed of spindled myoepithelial cells with adipose metaplasia.
Salivary gland myoepithelioma. The tumour is well circumscribed, encapsulated, and composed of myoepithelial cells.

Q: Architecturally, Salivary Gland Myoepithelioma characteristically presents as a non-invasive, well-circumscribed, and [...] tumor.
Salivary gland myoepithelioma. Well-circumscribed, non-invasive tumour surrounded by a capsule composed of spindle-shaped cells with myoepithelial differentiation.
Salivary gland myoepithelioma. The tumour is well circumscribed, encapsulated, and composed of myoepithelial cells.
A: encapsulated
Back Extra: Salivary Gland Myoepithelioma
- Clinical: Salivary Gland Myoepithelioma presents as a painless slow-growing mass, affects both sexes equally, and is most common in middle-aged individuals.
- Micro: The tumour is well-circumscribed and encapsulated, composed of myoepithelial cells with variable morphology (spindled, epithelioid, plasmacytoid, or clear).
- Ancillary: Positive for keratins, S100, SOX10, and myoepithelial markers like p63, calponin, and SMA; PLAG1 rearrangement may be detected.
Reference Gallery:
Salivary gland myoepithelioma. Epithelioid and plasmacytoid myoepithelial cells.
Salivary gland myoepithelioma. Well-circumscribed, non-invasive tumour surrounded by a capsule composed of spindle-shaped cells with myoepithelial differentiation.
Salivary gland myoepithelioma. Spindle cell with adipose metaplasia. The tumour is composed of spindled myoepithelial cells with adipose metaplasia.
Salivary gland myoepithelioma. The tumour is well circumscribed, encapsulated, and composed of myoepithelial cells.

Q: Histologically, Oncocytoma typically presents as a well-circumscribed tumor composed of sheets of large, bland cells with abundant [...] cytoplasm.
Oncocytoma. Oncocytoma of the parotid gland. The tumour is composed predominantly of sheets of oncocytes, large bland cells with eosinophilic granular cytoplasm.
Oncocytoma. Sheets of monomorphic cells with oncocytic cytoplasm.
A: eosinophilic granular
Back Extra: Oncocytoma
- Clinical: Oncocytomas most commonly occur in the parotid gland, presenting as a unilateral painless swelling in the seventh decade of life.
- Micro: Oncocytomas are well-circumscribed tumors consisting of oncocytes with abundant eosinophilic granular cytoplasm arranged in nests and sheets.
- Ancillary: The presence of p63-positive basal cells and absence of PAX2 and PAX8 expression are important markers for oncocytoma.
Reference Gallery:
Oncocytoma. Several p63+ basal cells.
Oncocytoma. Oncocytoma of the parotid gland. The tumour is composed predominantly of sheets of oncocytes, large bland cells with eosinophilic granular cytoplasm.
Oncocytoma. Sheets of monomorphic cells with oncocytic cytoplasm.

Q: In Oncocytoma, ancillary immunohistochemical testing classically highlights the presence of scattered [...]-positive basal cells.
Oncocytoma. Several p63+ basal cells.
A: p63
Back Extra: Oncocytoma
- Clinical: Oncocytomas most commonly occur in the parotid gland, presenting as a unilateral painless swelling in the seventh decade of life.
- Micro: Oncocytomas are well-circumscribed tumors consisting of oncocytes with abundant eosinophilic granular cytoplasm arranged in nests and sheets.
- Ancillary: The presence of p63-positive basal cells and absence of PAX2 and PAX8 expression are important markers for oncocytoma.
Reference Gallery:
Oncocytoma. Several p63+ basal cells.
Oncocytoma. Oncocytoma of the parotid gland. The tumour is composed predominantly of sheets of oncocytes, large bland cells with eosinophilic granular cytoplasm.
Oncocytoma. Sheets of monomorphic cells with oncocytic cytoplasm.

Q: Pleomorphic Adenoma is histologically defined by a biphasic proliferation of ductal and myoepithelial cells embedded within a characteristic [...] stroma.
Pleomorphic adenoma. The classic histological features are seen, with a chondromyxoid matrix blending imperceptibly with the myoepithelial cells and showing small ducts in the background.
Pleomorphic adenoma. The imperceptible blending of the components of pleomorphic adenoma are an aid to diagnosis. Small ducts are seen, surrounded by myoepithelial cells that merge into the adjacent chondromyxoid matrix.
A: chondromyxoid
Back Extra: Pleomorphic Adenoma
- Clinical: Pleomorphic adenomas typically present as slowly growing, painless masses, often in the parotid gland. Recurrent lesions can present as multinodular disease.
- Micro: Histologically, pleomorphic adenomas are characterized by an admixture of ductal and myoepithelial cells within a chondromyxoid stroma, with variable cellularity and stromal components.
- Ancillary: PLAG1 and HMGA2 are sensitive immunohistochemical markers for pleomorphic adenomas, with gene fusions involving these genes common in these tumors.
Reference Gallery:
Pleomorphic adenoma. Capsular invasion by pseudopodia.
Pleomorphic adenoma. FNAC. Giemsa stain showing myoepithelial and ductal cells in a background of magenta fibrillary matrix.
Pleomorphic adenoma. FNAC (Pap) showing myoepithelial and ductal cells in a background of fibrillary matrix.
Pleomorphic adenoma. This slowly growing mass had been present for > 10 years. There is no ulceration or erythema of the skin.
Pleomorphic adenoma. This ultrasound shows a well-defined, solid mass that is hypoechoic compared with adjacent salivary tissue, with homogeneous internal echoes.
Pleomorphic adenoma. Classic marked hyperintensity (similar intensity to cerebrospinal fluid) on a T2-weighted fat-suppressed protocol. This right retropharyngeal mass shows connection to the deep lobe of the parotid gland.
Pleomorphic adenoma. The classic histological features are seen, with a chondromyxoid matrix blending imperceptibly with the myoepithelial cells and showing small ducts in the background.
Pleomorphic adenoma. The imperceptible blending of the components of pleomorphic adenoma are an aid to diagnosis. Small ducts are seen, surrounded by myoepithelial cells that merge into the adjacent chondromyxoid matrix.
Pleomorphic adenoma. Clinically recurrent tumours demonstrate numerous nodules of pleomorphic adenoma set within fibrous connective tissue and fat. The cellularity is variable. There is no destructive infiltration and there is a lack of pleomorphism.
Pleomorphic adenoma. Many tumours are sampled by core needle biopsy. When all of the elements are present, a diagnosis can be made, while recognizing the sampling limitations.
Pleomorphic adenoma. High-power view of the core needle sample demonstrates the characteristic features of pleomorphic adenoma.
Pleomorphic adenoma. Tumours show remarkable variation in appearance, with a prominent spindled cell myoepithelial component illustrated. Focal squamous metaplasia is present.

Q: Pleomorphic Adenoma can recur if incompletely excised (often due to microscopic capsular pseudopodia), classically presenting as recurrent [...] disease.
Pleomorphic adenoma. Capsular invasion by pseudopodia.
Pleomorphic adenoma. Clinically recurrent tumours demonstrate numerous nodules of pleomorphic adenoma set within fibrous connective tissue and fat. The cellularity is variable. There is no destructive infiltration and there is a lack of pleomorphism.
A: multinodular
Back Extra: Pleomorphic Adenoma
- Clinical: Pleomorphic adenomas typically present as slowly growing, painless masses, often in the parotid gland. Recurrent lesions can present as multinodular disease.
- Micro: Histologically, pleomorphic adenomas are characterized by an admixture of ductal and myoepithelial cells within a chondromyxoid stroma, with variable cellularity and stromal components.
- Ancillary: PLAG1 and HMGA2 are sensitive immunohistochemical markers for pleomorphic adenomas, with gene fusions involving these genes common in these tumors.
Reference Gallery:
Pleomorphic adenoma. Capsular invasion by pseudopodia.
Pleomorphic adenoma. FNAC. Giemsa stain showing myoepithelial and ductal cells in a background of magenta fibrillary matrix.
Pleomorphic adenoma. FNAC (Pap) showing myoepithelial and ductal cells in a background of fibrillary matrix.
Pleomorphic adenoma. This slowly growing mass had been present for > 10 years. There is no ulceration or erythema of the skin.
Pleomorphic adenoma. This ultrasound shows a well-defined, solid mass that is hypoechoic compared with adjacent salivary tissue, with homogeneous internal echoes.
Pleomorphic adenoma. Classic marked hyperintensity (similar intensity to cerebrospinal fluid) on a T2-weighted fat-suppressed protocol. This right retropharyngeal mass shows connection to the deep lobe of the parotid gland.
Pleomorphic adenoma. The classic histological features are seen, with a chondromyxoid matrix blending imperceptibly with the myoepithelial cells and showing small ducts in the background.
Pleomorphic adenoma. The imperceptible blending of the components of pleomorphic adenoma are an aid to diagnosis. Small ducts are seen, surrounded by myoepithelial cells that merge into the adjacent chondromyxoid matrix.
Pleomorphic adenoma. Clinically recurrent tumours demonstrate numerous nodules of pleomorphic adenoma set within fibrous connective tissue and fat. The cellularity is variable. There is no destructive infiltration and there is a lack of pleomorphism.
Pleomorphic adenoma. Many tumours are sampled by core needle biopsy. When all of the elements are present, a diagnosis can be made, while recognizing the sampling limitations.
Pleomorphic adenoma. High-power view of the core needle sample demonstrates the characteristic features of pleomorphic adenoma.
Pleomorphic adenoma. Tumours show remarkable variation in appearance, with a prominent spindled cell myoepithelial component illustrated. Focal squamous metaplasia is present.

Q: Pleomorphic Adenoma on fine needle aspiration (FNA) classically demonstrates an admixture of myoepithelial and ductal cells within a fibrillary matrix that stains prominently [...] on a Giemsa stain.
Pleomorphic adenoma. FNAC. Giemsa stain showing myoepithelial and ductal cells in a background of magenta fibrillary matrix.
Pleomorphic adenoma. FNAC (Pap) showing myoepithelial and ductal cells in a background of fibrillary matrix.
A: magenta
Back Extra: Pleomorphic Adenoma
- Clinical: Pleomorphic adenomas typically present as slowly growing, painless masses, often in the parotid gland. Recurrent lesions can present as multinodular disease.
- Micro: Histologically, pleomorphic adenomas are characterized by an admixture of ductal and myoepithelial cells within a chondromyxoid stroma, with variable cellularity and stromal components.
- Ancillary: PLAG1 and HMGA2 are sensitive immunohistochemical markers for pleomorphic adenomas, with gene fusions involving these genes common in these tumors.
Reference Gallery:
Pleomorphic adenoma. Capsular invasion by pseudopodia.
Pleomorphic adenoma. FNAC. Giemsa stain showing myoepithelial and ductal cells in a background of magenta fibrillary matrix.
Pleomorphic adenoma. FNAC (Pap) showing myoepithelial and ductal cells in a background of fibrillary matrix.
Pleomorphic adenoma. This slowly growing mass had been present for > 10 years. There is no ulceration or erythema of the skin.
Pleomorphic adenoma. This ultrasound shows a well-defined, solid mass that is hypoechoic compared with adjacent salivary tissue, with homogeneous internal echoes.
Pleomorphic adenoma. Classic marked hyperintensity (similar intensity to cerebrospinal fluid) on a T2-weighted fat-suppressed protocol. This right retropharyngeal mass shows connection to the deep lobe of the parotid gland.
Pleomorphic adenoma. The classic histological features are seen, with a chondromyxoid matrix blending imperceptibly with the myoepithelial cells and showing small ducts in the background.
Pleomorphic adenoma. The imperceptible blending of the components of pleomorphic adenoma are an aid to diagnosis. Small ducts are seen, surrounded by myoepithelial cells that merge into the adjacent chondromyxoid matrix.
Pleomorphic adenoma. Clinically recurrent tumours demonstrate numerous nodules of pleomorphic adenoma set within fibrous connective tissue and fat. The cellularity is variable. There is no destructive infiltration and there is a lack of pleomorphism.
Pleomorphic adenoma. Many tumours are sampled by core needle biopsy. When all of the elements are present, a diagnosis can be made, while recognizing the sampling limitations.
Pleomorphic adenoma. High-power view of the core needle sample demonstrates the characteristic features of pleomorphic adenoma.
Pleomorphic adenoma. Tumours show remarkable variation in appearance, with a prominent spindled cell myoepithelial component illustrated. Focal squamous metaplasia is present.

Q: Histologically, Sclerosing Polycystic Adenoma is characterized by heavy stromal sclerosis, cystic ducts lined by apocrine or foamy epithelium, and large acinar cells containing characteristic [...].
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. An intermediate-power image shows heavy stromal sclerosis with cystic dilatation of hyperplastic-appearing epithelium showing ducts and acinar cells. Apocrine change is present, and foamy cytoplasm is seen in degenerating cells.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. Eosinophilic, spherical laminated hyaline globules are noted in association with epithelial nests, which also have cells with prominent eosinophilic cytoplasmic granules.
A: eosinophilic cytoplasmic granules
Back Extra: Sclerosing Polycystic Adenoma
- Clinical: Sclerosing Polycystic Adenoma (SPA) is a slow-growing, painless mass, rarely multifocal, with a slight female predominance and a mean age of presentation of 40 years.
- Micro: SPA is characterized by a cystic and multilobular pattern, with large acinar cells containing eosinophilic cytoplasmic granules, and variably sized ducts lined by apocrine or foamy epithelium.
- Ancillary: Immunohistochemistry shows loss of PTEN expression in ductal and apocrine elements, while myoepithelial cells retain PTEN expression.
Reference Gallery:
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. An intermediate-power image shows heavy stromal sclerosis with cystic dilatation of hyperplastic-appearing epithelium showing ducts and acinar cells. Apocrine change is present, and foamy cytoplasm is seen in degenerating cells.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. Eosinophilic, spherical laminated hyaline globules are noted in association with epithelial nests, which also have cells with prominent eosinophilic cytoplasmic granules.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. This case shows a mixed population of acinar cells and ducts in a fibrous stroma. The cystic duct in the centre shows apocrine hyperplasia that, by itself, is indistinguishable from apocrine intraductal carcinoma.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. PTEN immunohistochemistry shows an abnormal loss of expression in the ductal and apocrine elements but retained staining in the stromal and myoepithelial cells.
Sclerosing polycystic adenoma. Foci of homogeneous solid, micropapillary, and cribriform intraductal epithelial proliferations reminiscent of the intercalated duct cell variant of intraductal carcinoma. The intraductal proliferations are composed of intercalated duct cell–like epithelium and show solid and cribriform patterns.
Sclerosing polycystic adenoma. The intraductal proliferations show rigid bridging and cribriform patterns and are composed of intercalated duct cell–like epithelium positive for SOX10.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. Closely attached solid, tubular, and cribriform epithelial proliferations are composed of apocrine cells with nuclear atypia and finely granular cytoplasm. These cells are positive for AR and negative for SOX10.

Q: Immunohistochemistry in Sclerosing Polycystic Adenoma characteristically shows an abnormal loss of [...] expression in the ductal and apocrine elements, while staining is retained in the surrounding stromal and myoepithelial cells.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. PTEN immunohistochemistry shows an abnormal loss of expression in the ductal and apocrine elements but retained staining in the stromal and myoepithelial cells.
A: PTEN
Back Extra: Sclerosing Polycystic Adenoma
- Clinical: Sclerosing Polycystic Adenoma (SPA) is a slow-growing, painless mass, rarely multifocal, with a slight female predominance and a mean age of presentation of 40 years.
- Micro: SPA is characterized by a cystic and multilobular pattern, with large acinar cells containing eosinophilic cytoplasmic granules, and variably sized ducts lined by apocrine or foamy epithelium.
- Ancillary: Immunohistochemistry shows loss of PTEN expression in ductal and apocrine elements, while myoepithelial cells retain PTEN expression.
Reference Gallery:
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. An intermediate-power image shows heavy stromal sclerosis with cystic dilatation of hyperplastic-appearing epithelium showing ducts and acinar cells. Apocrine change is present, and foamy cytoplasm is seen in degenerating cells.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. Eosinophilic, spherical laminated hyaline globules are noted in association with epithelial nests, which also have cells with prominent eosinophilic cytoplasmic granules.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. This case shows a mixed population of acinar cells and ducts in a fibrous stroma. The cystic duct in the centre shows apocrine hyperplasia that, by itself, is indistinguishable from apocrine intraductal carcinoma.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. PTEN immunohistochemistry shows an abnormal loss of expression in the ductal and apocrine elements but retained staining in the stromal and myoepithelial cells.
Sclerosing polycystic adenoma. Foci of homogeneous solid, micropapillary, and cribriform intraductal epithelial proliferations reminiscent of the intercalated duct cell variant of intraductal carcinoma. The intraductal proliferations are composed of intercalated duct cell–like epithelium and show solid and cribriform patterns.
Sclerosing polycystic adenoma. The intraductal proliferations show rigid bridging and cribriform patterns and are composed of intercalated duct cell–like epithelium positive for SOX10.
Sclerosing polycystic adenoma. Salivary sclerosing polycystic adenoma. Closely attached solid, tubular, and cribriform epithelial proliferations are composed of apocrine cells with nuclear atypia and finely granular cytoplasm. These cells are positive for AR and negative for SOX10.

Q: Microscopically, a Sebaceous Adenoma presents as a well-circumscribed tumor composed of irregularly sized nests that demonstrate prominent [...] differentiation, often forming cystic spaces that previously contained sebum.
Sebaceous adenoma. The tumour is encapsulated and is composed of numerous closely associated nests with prominent sebaceous differentiation. The cystic spaces previously contained sebum.
Sebaceous adenoma. Nests of cells exhibiting prominent sebaceous differentiation.
A: sebaceous
Back Extra: Sebaceous Adenoma
- Clinical: Sebaceous adenoma typically presents as a painless mass in the sixth decade of life, more commonly in males, and predominantly in the parotid gland.
- Micro: Characterized by irregularly sized nests of sebaceous cells with cystic changes and squamous differentiation, without significant atypia or pleomorphism.
- Ancillary: Ancillary studies are generally not required for diagnosis, as the morphological features are distinct.
Reference Gallery:
Sebaceous adenoma. The tumour is encapsulated and is composed of numerous closely associated nests with prominent sebaceous differentiation. The cystic spaces previously contained sebum.
Sebaceous adenoma. Nests of cells exhibiting prominent sebaceous differentiation.
Sebaceous adenoma. A smear showing a minute tissue fragment of large vacuolated epithelial cells with centrally located scalloped nuclei (FNAB, Giemsa).

Q: On fine needle aspiration (FNA) cytology, a Sebaceous Adenoma yields minute tissue fragments composed of large, [...] epithelial cells with centrally located, scalloped nuclei.
Sebaceous adenoma. A smear showing a minute tissue fragment of large vacuolated epithelial cells with centrally located scalloped nuclei (FNAB, Giemsa).
A: vacuolated
Back Extra: Sebaceous Adenoma
- Clinical: Sebaceous adenoma typically presents as a painless mass in the sixth decade of life, more commonly in males, and predominantly in the parotid gland.
- Micro: Characterized by irregularly sized nests of sebaceous cells with cystic changes and squamous differentiation, without significant atypia or pleomorphism.
- Ancillary: Ancillary studies are generally not required for diagnosis, as the morphological features are distinct.
Reference Gallery:
Sebaceous adenoma. The tumour is encapsulated and is composed of numerous closely associated nests with prominent sebaceous differentiation. The cystic spaces previously contained sebum.
Sebaceous adenoma. Nests of cells exhibiting prominent sebaceous differentiation.
Sebaceous adenoma. A smear showing a minute tissue fragment of large vacuolated epithelial cells with centrally located scalloped nuclei (FNAB, Giemsa).

Q: Histologically, Sialadenoma Papilliferum is characterized by a biphasic growth pattern consisting of an [...] and an endophytic ductal papillary proliferation.
Sialadenoma papilliferum. At low magnification, sialadenoma papilliferum is characterized by the presence of exophytic and endophytic components.
Sialadenoma papilliferum. The upper exophytic part shows a papillary proliferation of squamous cells mixed with ductal cells. The lower part shows the ductal component with a cystic-papillary pattern.
A: exophytic squamous
Back Extra: Sialadenoma Papilliferum
- Clinical: Sialadenoma papilliferum typically presents as a raised, sessile or pedunculated mucosal lesion, most commonly in older adults with a male predominance.
- Micro: The histopathology of sialadenoma papilliferum is characterized by exophytic squamous and endophytic ductal papillary proliferation, often with cystic-like spaces and a lymphoplasmacytic stromal infiltrate.
- Ancillary: Both the squamous and ductal components of sialadenoma papilliferum are positive for BRAF p.V600E by immunohistochemistry, which is a useful diagnostic marker.
Reference Gallery:
Sialadenoma papilliferum. At low magnification, sialadenoma papilliferum is characterized by the presence of exophytic and endophytic components.
Sialadenoma papilliferum. The upper exophytic part shows a papillary proliferation of squamous cells mixed with ductal cells. The lower part shows the ductal component with a cystic-papillary pattern.
Sialadenoma papilliferum. The ductal component has p63-positive basal cells.
Sialadenoma papilliferum. Both the squamous and ductal components are positive for BRAF p.V600E by immunohistochemistry.

Q: In Sialadenoma Papilliferum, immunohistochemistry typically reveals that both the squamous and ductal components are positive for [...].
Sialadenoma papilliferum. Both the squamous and ductal components are positive for BRAF p.V600E by immunohistochemistry.
A: BRAF p.V600E
Back Extra: Sialadenoma Papilliferum
- Clinical: Sialadenoma papilliferum typically presents as a raised, sessile or pedunculated mucosal lesion, most commonly in older adults with a male predominance.
- Micro: The histopathology of sialadenoma papilliferum is characterized by exophytic squamous and endophytic ductal papillary proliferation, often with cystic-like spaces and a lymphoplasmacytic stromal infiltrate.
- Ancillary: Both the squamous and ductal components of sialadenoma papilliferum are positive for BRAF p.V600E by immunohistochemistry, which is a useful diagnostic marker.
Reference Gallery:
Sialadenoma papilliferum. At low magnification, sialadenoma papilliferum is characterized by the presence of exophytic and endophytic components.
Sialadenoma papilliferum. The upper exophytic part shows a papillary proliferation of squamous cells mixed with ductal cells. The lower part shows the ductal component with a cystic-papillary pattern.
Sialadenoma papilliferum. The ductal component has p63-positive basal cells.
Sialadenoma papilliferum. Both the squamous and ductal components are positive for BRAF p.V600E by immunohistochemistry.

Q: The endophytic ductal component of Sialadenoma Papilliferum typically maintains an intact layer of basal cells that are positive for [...] by immunohistochemistry.
Sialadenoma papilliferum. The ductal component has p63-positive basal cells.
A: p63
Back Extra: Sialadenoma Papilliferum
- Clinical: Sialadenoma papilliferum typically presents as a raised, sessile or pedunculated mucosal lesion, most commonly in older adults with a male predominance.
- Micro: The histopathology of sialadenoma papilliferum is characterized by exophytic squamous and endophytic ductal papillary proliferation, often with cystic-like spaces and a lymphoplasmacytic stromal infiltrate.
- Ancillary: Both the squamous and ductal components of sialadenoma papilliferum are positive for BRAF p.V600E by immunohistochemistry, which is a useful diagnostic marker.
Reference Gallery:
Sialadenoma papilliferum. At low magnification, sialadenoma papilliferum is characterized by the presence of exophytic and endophytic components.
Sialadenoma papilliferum. The upper exophytic part shows a papillary proliferation of squamous cells mixed with ductal cells. The lower part shows the ductal component with a cystic-papillary pattern.
Sialadenoma papilliferum. The ductal component has p63-positive basal cells.
Sialadenoma papilliferum. Both the squamous and ductal components are positive for BRAF p.V600E by immunohistochemistry.

Q: Sialolipoma is a well-circumscribed tumor that classically combines lobules of normal salivary parenchyma with a dominating and evenly interspersed [...] component.
Sialolipoma. Isolated salivary gland elements are seen within a predominantly adipocytic proliferation. A well-developed capsule was seen around the periphery.
Sialolipoma of the parotid gland. Isolated salivary gland elements are seen within a predominantly adipocytic proliferation. A well-developed capsule was seen around the periphery.
A: adipose tissue
Back Extra: Sialolipoma
- Clinical: Patients typically present with a slow-growing swelling in the salivary gland, with an equal sex distribution and a mean age of 51.5 years at presentation.
- Micro: Sialolipomas are well-circumscribed tumors combining lobules of salivary parenchyma with a dominating and evenly interspersed adipose tissue component.
- Ancillary: Cytological preparations may show mature adipocytic and salivary epithelial elements in varying proportions.
Reference Gallery:
Sialolipoma. Isolated salivary gland elements are seen within a predominantly adipocytic proliferation. A well-developed capsule was seen around the periphery.
Sialolipoma of the parotid gland. Isolated salivary gland elements are seen within a predominantly adipocytic proliferation. A well-developed capsule was seen around the periphery.
Oncocytic lipoadenoma. The tumour consists of salivary gland lobules with oncocytic features and mature adipose tissue. A well-developed capsule was seen around the periphery.

Q: Sialolipoma typically features a well-developed peripheral capsule surrounding a predominantly adipocytic proliferation that entraps isolated [...] elements.
Sialolipoma. Isolated salivary gland elements are seen within a predominantly adipocytic proliferation. A well-developed capsule was seen around the periphery.
Sialolipoma of the parotid gland. Isolated salivary gland elements are seen within a predominantly adipocytic proliferation. A well-developed capsule was seen around the periphery.
A: salivary gland
Back Extra: Sialolipoma
- Clinical: Patients typically present with a slow-growing swelling in the salivary gland, with an equal sex distribution and a mean age of 51.5 years at presentation.
- Micro: Sialolipomas are well-circumscribed tumors combining lobules of salivary parenchyma with a dominating and evenly interspersed adipose tissue component.
- Ancillary: Cytological preparations may show mature adipocytic and salivary epithelial elements in varying proportions.
Reference Gallery:
Sialolipoma. Isolated salivary gland elements are seen within a predominantly adipocytic proliferation. A well-developed capsule was seen around the periphery.
Sialolipoma of the parotid gland. Isolated salivary gland elements are seen within a predominantly adipocytic proliferation. A well-developed capsule was seen around the periphery.
Oncocytic lipoadenoma. The tumour consists of salivary gland lobules with oncocytic features and mature adipose tissue. A well-developed capsule was seen around the periphery.

Q: Striated Duct Adenoma is a well-circumscribed tumor composed of a pure, unilayered population of eosinophilic ducts with minimal intervening stroma, and its intraluminal secretions can uniquely resemble [...].
Striated duct adenoma. Low-power image of a striated duct adenoma with variable small-calibre ducts and microcysts.
Striated duct adenoma. The tumours are made of a pure population of eosinophilic ducts with minimal intervening stroma. Some lumina contain numerous red blood cells.
Striated duct adenoma. The majority of the ductal spaces are similarly sized to normal striated ducts and have bland nuclei. Luminal secretions may resemble colloid.
A: colloid
Back Extra: Striated Duct Adenoma
- Clinical: Striated duct adenomas (SDA) present as painless masses in adults (age range: 47–78 years) with a slight female predominance.
- Micro: SDAs are well-circumscribed, encapsulated masses composed of small, closely spaced ducts with minimal intervening stroma. The ducts are lined by a single layer of columnar cells with eosinophilic cytoplasm.
- Ancillary: SDAs are strongly positive for keratins (CK7, CK5/6) and S100, with only focal staining for basal markers like p63 and calponin.
Reference Gallery:
Striated duct adenoma. Low-power image of a striated duct adenoma with variable small-calibre ducts and microcysts.
Striated duct adenoma. The tumours are made of a pure population of eosinophilic ducts with minimal intervening stroma. Some lumina contain numerous red blood cells.
Striated duct adenoma. The majority of the ductal spaces are similarly sized to normal striated ducts and have bland nuclei. Luminal secretions may resemble colloid.
Striated duct adenoma. These tumours are diffusely positive for S100, unlike their closest mimics, namely oncocytomas.
Striated duct adenoma. Striated duct adenomas are unilayered, with minimal contribution from basal or myoepithelial cells. Therefore, p63 immunohistochemistry stains only focal abluminal cells, if any.
Striated duct adenoma. Calponin (shown here) or actins show only focal abluminal staining, if any, in striated duct adenoma.

Q: To distinguish Striated Duct Adenoma from its closest morphologic mimic, oncocytoma, immunohistochemistry can be used, as it is characteristically and diffusely positive for [...].
Striated duct adenoma. These tumours are diffusely positive for S100, unlike their closest mimics, namely oncocytomas.
A: S100
Back Extra: Striated Duct Adenoma
- Clinical: Striated duct adenomas (SDA) present as painless masses in adults (age range: 47–78 years) with a slight female predominance.
- Micro: SDAs are well-circumscribed, encapsulated masses composed of small, closely spaced ducts with minimal intervening stroma. The ducts are lined by a single layer of columnar cells with eosinophilic cytoplasm.
- Ancillary: SDAs are strongly positive for keratins (CK7, CK5/6) and S100, with only focal staining for basal markers like p63 and calponin.
Reference Gallery:
Striated duct adenoma. Low-power image of a striated duct adenoma with variable small-calibre ducts and microcysts.
Striated duct adenoma. The tumours are made of a pure population of eosinophilic ducts with minimal intervening stroma. Some lumina contain numerous red blood cells.
Striated duct adenoma. The majority of the ductal spaces are similarly sized to normal striated ducts and have bland nuclei. Luminal secretions may resemble colloid.
Striated duct adenoma. These tumours are diffusely positive for S100, unlike their closest mimics, namely oncocytomas.
Striated duct adenoma. Striated duct adenomas are unilayered, with minimal contribution from basal or myoepithelial cells. Therefore, p63 immunohistochemistry stains only focal abluminal cells, if any.
Striated duct adenoma. Calponin (shown here) or actins show only focal abluminal staining, if any, in striated duct adenoma.

Q: Because the eosinophilic ducts of Striated Duct Adenoma are primarily unilayered, immunohistochemistry for basal and myoepithelial markers like calponin and [...] will typically show only focal or absent abluminal staining.
Striated duct adenoma. Striated duct adenomas are unilayered, with minimal contribution from basal or myoepithelial cells. Therefore, p63 immunohistochemistry stains only focal abluminal cells, if any.
Striated duct adenoma. Calponin (shown here) or actins show only focal abluminal staining, if any, in striated duct adenoma.
A: p63
Back Extra: Striated Duct Adenoma
- Clinical: Striated duct adenomas (SDA) present as painless masses in adults (age range: 47–78 years) with a slight female predominance.
- Micro: SDAs are well-circumscribed, encapsulated masses composed of small, closely spaced ducts with minimal intervening stroma. The ducts are lined by a single layer of columnar cells with eosinophilic cytoplasm.
- Ancillary: SDAs are strongly positive for keratins (CK7, CK5/6) and S100, with only focal staining for basal markers like p63 and calponin.
Reference Gallery:
Striated duct adenoma. Low-power image of a striated duct adenoma with variable small-calibre ducts and microcysts.
Striated duct adenoma. The tumours are made of a pure population of eosinophilic ducts with minimal intervening stroma. Some lumina contain numerous red blood cells.
Striated duct adenoma. The majority of the ductal spaces are similarly sized to normal striated ducts and have bland nuclei. Luminal secretions may resemble colloid.
Striated duct adenoma. These tumours are diffusely positive for S100, unlike their closest mimics, namely oncocytomas.
Striated duct adenoma. Striated duct adenomas are unilayered, with minimal contribution from basal or myoepithelial cells. Therefore, p63 immunohistochemistry stains only focal abluminal cells, if any.
Striated duct adenoma. Calponin (shown here) or actins show only focal abluminal staining, if any, in striated duct adenoma.

Q: The hallmark microscopic finding in Warthin Tumor is the presence of papillary-cystic structures lined by a double layer of [...] cells set within a dense lymphoid stroma.
Warthin tumour. Numerous papillary structures are noted, lined by a double layer of oncocytically altered cells, all set within a very well developed lymphoid stroma.
Warthin tumour. The double-layered (tram-tracking) appearance of the oncocytically altered cells is quite characteristic, whether they line the cystic spaces or are arranged in papillae. Note the lymphoid stroma.
A: oncocytic
Back Extra: Warthin Tumor
- Clinical: Warthin tumors typically present as painless, slow-growing swellings in the parotid gland, more common in males and with a mean age of diagnosis around 62 years.
- Micro: Characterized by papillary-cystic structures lined by a double layer of oncocytic epithelial cells, surrounded by a lymphoid stroma with germinal centers.
- Ancillary: Absence of MAML2 rearrangement helps distinguish Warthin tumor from mucoepidermoid carcinoma.
Reference Gallery:
Warthin tumour. Gross image. A well-defined circumscribed tumour with a brown glistening homogeneous cut surface.
Warthin tumour. A smear showing a group of epithelial cells in a lymphoid background (FNAB, Pap).
Warthin tumour. Spaces lined by oncocytic epithelium, with surrounding lymphoid stroma.
Warthin tumour. Numerous papillary structures are noted, lined by a double layer of oncocytically altered cells, all set within a very well developed lymphoid stroma.
Warthin tumour. The double-layered (tram-tracking) appearance of the oncocytically altered cells is quite characteristic, whether they line the cystic spaces or are arranged in papillae. Note the lymphoid stroma.
Warthin tumour. Oncocytically altered tumours frequently undergo infarction or degeneration, especially after manipulation (FNA or core needle biopsy). However, papillary ghost cell outlines are noted, with degenerated lymphoid stroma adjacent.
Warthin tumour. Smears show small cohesive sheets of oncocytes, numerous lymphocytes, and granular background debris (FNAB, Pap).
Warthin tumour. Smears show numerous small cohesive sheets of oncocytes with lymphocytes in the background granular debris (FNAB, Giemsa).
Warthin tumour. The double-layered pattern of the oncocytic cells is quite characteristic, whether they line the cystic spaces or are arranged in papillae. Note the lymphoid stroma.
Warthin tumour. Papillary structures are noted, lined by a double layer of oncocytic cells, surrounded by well-developed lymphoid stroma.
Warthin tumour. Metaplastic Warthin tumour. The tumour is characterized by the replacement of the double layer of oncocytic cells by metaplastic epithelium.
Warthin tumour. Warthin tumour with mucinous metaplasia. Extensive mucinous metaplasia replacing bilayered papillary oncocytic epithelium.

Q: Fine-needle aspiration (FNA) of a Warthin Tumor classically reveals cohesive sheets of [...] mixed with a background of numerous lymphocytes and granular debris.
Warthin tumour. Smears show small cohesive sheets of oncocytes, numerous lymphocytes, and granular background debris (FNAB, Pap).
Warthin tumour. Smears show numerous small cohesive sheets of oncocytes with lymphocytes in the background granular debris (FNAB, Giemsa).
A: oncocytes
Back Extra: Warthin Tumor
- Clinical: Warthin tumors typically present as painless, slow-growing swellings in the parotid gland, more common in males and with a mean age of diagnosis around 62 years.
- Micro: Characterized by papillary-cystic structures lined by a double layer of oncocytic epithelial cells, surrounded by a lymphoid stroma with germinal centers.
- Ancillary: Absence of MAML2 rearrangement helps distinguish Warthin tumor from mucoepidermoid carcinoma.
Reference Gallery:
Warthin tumour. Gross image. A well-defined circumscribed tumour with a brown glistening homogeneous cut surface.
Warthin tumour. A smear showing a group of epithelial cells in a lymphoid background (FNAB, Pap).
Warthin tumour. Spaces lined by oncocytic epithelium, with surrounding lymphoid stroma.
Warthin tumour. Numerous papillary structures are noted, lined by a double layer of oncocytically altered cells, all set within a very well developed lymphoid stroma.
Warthin tumour. The double-layered (tram-tracking) appearance of the oncocytically altered cells is quite characteristic, whether they line the cystic spaces or are arranged in papillae. Note the lymphoid stroma.
Warthin tumour. Oncocytically altered tumours frequently undergo infarction or degeneration, especially after manipulation (FNA or core needle biopsy). However, papillary ghost cell outlines are noted, with degenerated lymphoid stroma adjacent.
Warthin tumour. Smears show small cohesive sheets of oncocytes, numerous lymphocytes, and granular background debris (FNAB, Pap).
Warthin tumour. Smears show numerous small cohesive sheets of oncocytes with lymphocytes in the background granular debris (FNAB, Giemsa).
Warthin tumour. The double-layered pattern of the oncocytic cells is quite characteristic, whether they line the cystic spaces or are arranged in papillae. Note the lymphoid stroma.
Warthin tumour. Papillary structures are noted, lined by a double layer of oncocytic cells, surrounded by well-developed lymphoid stroma.
Warthin tumour. Metaplastic Warthin tumour. The tumour is characterized by the replacement of the double layer of oncocytic cells by metaplastic epithelium.
Warthin tumour. Warthin tumour with mucinous metaplasia. Extensive mucinous metaplasia replacing bilayered papillary oncocytic epithelium.

Q: Grossly, a Warthin Tumor typically presents as a well-circumscribed mass with a solid or cystic cut surface that is classically [...] in color.
Warthin tumour. Gross image. A well-defined circumscribed tumour with a brown glistening homogeneous cut surface.
A: brown
Back Extra: Warthin Tumor
- Clinical: Warthin tumors typically present as painless, slow-growing swellings in the parotid gland, more common in males and with a mean age of diagnosis around 62 years.
- Micro: Characterized by papillary-cystic structures lined by a double layer of oncocytic epithelial cells, surrounded by a lymphoid stroma with germinal centers.
- Ancillary: Absence of MAML2 rearrangement helps distinguish Warthin tumor from mucoepidermoid carcinoma.
Reference Gallery:
Warthin tumour. Gross image. A well-defined circumscribed tumour with a brown glistening homogeneous cut surface.
Warthin tumour. A smear showing a group of epithelial cells in a lymphoid background (FNAB, Pap).
Warthin tumour. Spaces lined by oncocytic epithelium, with surrounding lymphoid stroma.
Warthin tumour. Numerous papillary structures are noted, lined by a double layer of oncocytically altered cells, all set within a very well developed lymphoid stroma.
Warthin tumour. The double-layered (tram-tracking) appearance of the oncocytically altered cells is quite characteristic, whether they line the cystic spaces or are arranged in papillae. Note the lymphoid stroma.
Warthin tumour. Oncocytically altered tumours frequently undergo infarction or degeneration, especially after manipulation (FNA or core needle biopsy). However, papillary ghost cell outlines are noted, with degenerated lymphoid stroma adjacent.
Warthin tumour. Smears show small cohesive sheets of oncocytes, numerous lymphocytes, and granular background debris (FNAB, Pap).
Warthin tumour. Smears show numerous small cohesive sheets of oncocytes with lymphocytes in the background granular debris (FNAB, Giemsa).
Warthin tumour. The double-layered pattern of the oncocytic cells is quite characteristic, whether they line the cystic spaces or are arranged in papillae. Note the lymphoid stroma.
Warthin tumour. Papillary structures are noted, lined by a double layer of oncocytic cells, surrounded by well-developed lymphoid stroma.
Warthin tumour. Metaplastic Warthin tumour. The tumour is characterized by the replacement of the double layer of oncocytic cells by metaplastic epithelium.
Warthin tumour. Warthin tumour with mucinous metaplasia. Extensive mucinous metaplasia replacing bilayered papillary oncocytic epithelium.

Q: A hallmark histologic feature of Acinic Cell Carcinoma is the presence of serous acinar cells containing abundant, PAS-positive, diastase-resistant [...] in their basophilic cytoplasm.
Acinic cell carcinoma. A basophilic, zymogen-rich example.
Acinic cell carcinoma. A mixture of zymogen-containing serous acinar and intercalated duct–type cells.
A: zymogen granules
Back Extra: Acinic Cell Carcinoma
- Clinical: Acinic cell carcinoma typically presents as a slow-growing, painless mass. High-grade tumours may be rapidly growing, fixed to adjacent structures, and associated with facial nerve paralysis.
- Micro: The tumour exhibits solid, microcystic, follicular, and papillary-cystic architectures. Neoplastic cells are heterogeneous, with serous acinar cells being the most common, featuring PAS-positive, diastase-resistant basophilic cytoplasmic zymogen granules.
- Ancillary: Acinic cell carcinoma cells express DOG1 and NR4A3 (NOR1), and are negative for p40/p63, mammaglobin, and S100. Molecular pathology is typically not needed for diagnosis, but NR4A subfamily rearrangements or positive immunohistochemistry for NR4A3 or NR4A2 may be confirmatory in challenging cases.
Reference Gallery:
Acinic cell carcinoma. A basophilic, zymogen-rich example.
Acinic cell carcinoma. A mixture of zymogen-containing serous acinar and intercalated duct–type cells.
Acinic cell carcinoma. Microcystic and follicular growth patterns.
Acinic cell carcinoma. Acinic cell carcinoma with high-grade transformation. High-grade tumour cells that feature nuclear enlargement and pleomorphism (upper right) can be seen admixed with conventional, low-grade tumour cells (lower left) in this high-grade example.
Acinic cell carcinoma. High-grade adenocarcinoma with necrosis in this acinic cell carcinoma with high-grade transformation.
Acinic cell carcinoma. Round to oval nuclei with delicate, vacuolated cytoplasm (FNAB, Pap).
Acinic cell carcinoma. The smear shows round to oval nuclei with delicate, vacuolated cytoplasm (FNAB, Pap). Characteristic coarse cytoplasmic zymogen granules that stain basophilic in Pap preparations may be seen (not shown).
Acinic cell carcinoma. DOG1 immunohistochemistry shows a membranous, canalicular or apical-luminal, and cytoplasmic reaction in the neoplastic cells of acinic cell carcinoma.
Acinic cell carcinoma. All of the neoplastic nuclei show strong and diffuse immunoreactivity for NR4A3 (endothelial cells are a negative internal control).
Acinic cell carcinoma. Nuclear expression of NR4A3 in the neoplastic acinar cells of acinic cell carcinoma with a lymphoid-rich stroma.
Acinic cell carcinoma. Strong nuclear expression of NR4A2 (NURR1) in neoplastic cells in an acinic cell carcinoma.

Q: In addition to DOG1 positivity, Acinic Cell Carcinoma is characterized by NR4A subfamily rearrangements, which can be confirmed by strong nuclear immunohistochemical expression of [...] (or NR4A2).
Acinic cell carcinoma. DOG1 immunohistochemistry shows a membranous, canalicular or apical-luminal, and cytoplasmic reaction in the neoplastic cells of acinic cell carcinoma.
Acinic cell carcinoma. All of the neoplastic nuclei show strong and diffuse immunoreactivity for NR4A3 (endothelial cells are a negative internal control).
Acinic cell carcinoma. Strong nuclear expression of NR4A2 (NURR1) in neoplastic cells in an acinic cell carcinoma.
A: NR4A3
Back Extra: Acinic Cell Carcinoma
- Clinical: Acinic cell carcinoma typically presents as a slow-growing, painless mass. High-grade tumours may be rapidly growing, fixed to adjacent structures, and associated with facial nerve paralysis.
- Micro: The tumour exhibits solid, microcystic, follicular, and papillary-cystic architectures. Neoplastic cells are heterogeneous, with serous acinar cells being the most common, featuring PAS-positive, diastase-resistant basophilic cytoplasmic zymogen granules.
- Ancillary: Acinic cell carcinoma cells express DOG1 and NR4A3 (NOR1), and are negative for p40/p63, mammaglobin, and S100. Molecular pathology is typically not needed for diagnosis, but NR4A subfamily rearrangements or positive immunohistochemistry for NR4A3 or NR4A2 may be confirmatory in challenging cases.
Reference Gallery:
Acinic cell carcinoma. A basophilic, zymogen-rich example.
Acinic cell carcinoma. A mixture of zymogen-containing serous acinar and intercalated duct–type cells.
Acinic cell carcinoma. Microcystic and follicular growth patterns.
Acinic cell carcinoma. Acinic cell carcinoma with high-grade transformation. High-grade tumour cells that feature nuclear enlargement and pleomorphism (upper right) can be seen admixed with conventional, low-grade tumour cells (lower left) in this high-grade example.
Acinic cell carcinoma. High-grade adenocarcinoma with necrosis in this acinic cell carcinoma with high-grade transformation.
Acinic cell carcinoma. Round to oval nuclei with delicate, vacuolated cytoplasm (FNAB, Pap).
Acinic cell carcinoma. The smear shows round to oval nuclei with delicate, vacuolated cytoplasm (FNAB, Pap). Characteristic coarse cytoplasmic zymogen granules that stain basophilic in Pap preparations may be seen (not shown).
Acinic cell carcinoma. DOG1 immunohistochemistry shows a membranous, canalicular or apical-luminal, and cytoplasmic reaction in the neoplastic cells of acinic cell carcinoma.
Acinic cell carcinoma. All of the neoplastic nuclei show strong and diffuse immunoreactivity for NR4A3 (endothelial cells are a negative internal control).
Acinic cell carcinoma. Nuclear expression of NR4A3 in the neoplastic acinar cells of acinic cell carcinoma with a lymphoid-rich stroma.
Acinic cell carcinoma. Strong nuclear expression of NR4A2 (NURR1) in neoplastic cells in an acinic cell carcinoma.

Q: On fine-needle aspiration (FNA) smears, the neoplastic cells of Acinic Cell Carcinoma typically feature round to oval nuclei with delicate, [...] cytoplasm.
Acinic cell carcinoma. Round to oval nuclei with delicate, vacuolated cytoplasm (FNAB, Pap).
Acinic cell carcinoma. The smear shows round to oval nuclei with delicate, vacuolated cytoplasm (FNAB, Pap). Characteristic coarse cytoplasmic zymogen granules that stain basophilic in Pap preparations may be seen (not shown).
A: vacuolated
Back Extra: Acinic Cell Carcinoma
- Clinical: Acinic cell carcinoma typically presents as a slow-growing, painless mass. High-grade tumours may be rapidly growing, fixed to adjacent structures, and associated with facial nerve paralysis.
- Micro: The tumour exhibits solid, microcystic, follicular, and papillary-cystic architectures. Neoplastic cells are heterogeneous, with serous acinar cells being the most common, featuring PAS-positive, diastase-resistant basophilic cytoplasmic zymogen granules.
- Ancillary: Acinic cell carcinoma cells express DOG1 and NR4A3 (NOR1), and are negative for p40/p63, mammaglobin, and S100. Molecular pathology is typically not needed for diagnosis, but NR4A subfamily rearrangements or positive immunohistochemistry for NR4A3 or NR4A2 may be confirmatory in challenging cases.
Reference Gallery:
Acinic cell carcinoma. A basophilic, zymogen-rich example.
Acinic cell carcinoma. A mixture of zymogen-containing serous acinar and intercalated duct–type cells.
Acinic cell carcinoma. Microcystic and follicular growth patterns.
Acinic cell carcinoma. Acinic cell carcinoma with high-grade transformation. High-grade tumour cells that feature nuclear enlargement and pleomorphism (upper right) can be seen admixed with conventional, low-grade tumour cells (lower left) in this high-grade example.
Acinic cell carcinoma. High-grade adenocarcinoma with necrosis in this acinic cell carcinoma with high-grade transformation.
Acinic cell carcinoma. Round to oval nuclei with delicate, vacuolated cytoplasm (FNAB, Pap).
Acinic cell carcinoma. The smear shows round to oval nuclei with delicate, vacuolated cytoplasm (FNAB, Pap). Characteristic coarse cytoplasmic zymogen granules that stain basophilic in Pap preparations may be seen (not shown).
Acinic cell carcinoma. DOG1 immunohistochemistry shows a membranous, canalicular or apical-luminal, and cytoplasmic reaction in the neoplastic cells of acinic cell carcinoma.
Acinic cell carcinoma. All of the neoplastic nuclei show strong and diffuse immunoreactivity for NR4A3 (endothelial cells are a negative internal control).
Acinic cell carcinoma. Nuclear expression of NR4A3 in the neoplastic acinar cells of acinic cell carcinoma with a lymphoid-rich stroma.
Acinic cell carcinoma. Strong nuclear expression of NR4A2 (NURR1) in neoplastic cells in an acinic cell carcinoma.

Q: Histologically, Adenoid Cystic Carcinoma is classically characterized by a [...] growth pattern with pseudocysts, often described as having a "Swiss-cheese" or "telephone-dial" appearance.
Adenoid cystic carcinoma. Cribriform pattern (MYB::NFIB-positive case). Myoepithelial tumour cells with clear cytoplasm and angular nuclei surround multiple cyst-like areas (pseudocysts) that are contiguous with the stroma of the neoplasm (arrow). A small lumen surrounded by eosinophilic, cuboidal cells (asterisk) indicates a focus of true ductal differentiation.
Adenoid cystic carcinoma. The cribriform pattern of adenoid cystic carcinoma is one of the most helpful features in the diagnosis. This image shows glycosaminoglycan material creating the Swiss-cheese or telephone-dial appearance. Note the stromal-epithelial clefting.
A: cribriform
Q: Adenoid Cystic Carcinoma
- Clinical: Patients with [...] usually present with a slow-growing mass and may have neural symptoms such as pain, numbness, and paraesthesia.
- Micro: [...] is characterized by a cribriform pattern with pseudocysts and a basophilic matrix, and often shows perineural invasion.
- Ancillary: MYB or NFIB rearrangements are common in [...] and can be detected by FISH or other methods.
Reference Gallery:
Adenoid cystic carcinoma. Gross photograph showing a firm, unencapsulated, and infiltrative mass with a greyish-white, homogeneous cut surface in the left parotid gland.
Adenoid cystic carcinoma. Cribriform pattern (MYB::NFIB-positive case). Myoepithelial tumour cells with clear cytoplasm and angular nuclei surround multiple cyst-like areas (pseudocysts) that are contiguous with the stroma of the neoplasm (arrow). A small lumen surrounded by eosinophilic, cuboidal cells (asterisk) indicates a focus of true ductal differentiation.
Adenoid cystic carcinoma, solid pattern (MYB::NFIB-positive case). The solid pattern is characterized by dense cellular tumour nests lacking the pseudocystic spaces observed in the cribriform and tubular patterns.
Adenoid cystic carcinoma, high-grade transformation (MYB::NFIB-positive case). A typical cribriform tumour nest (asterisk) is surrounded by tumour nests best characterized as poorly differentiated adenocarcinoma.
Adenoid cystic carcinoma. A MYB::NFIB-positive case. The tumour shows prominent perineural and intraneural invasion.
Adenoid cystic carcinoma. The FNA smear demonstrates the characteristic discrete spheres and branching tubules of the acellular magenta matrix (Romanowsky–Giemsa stain).
Adenoid cystic carcinoma. Cribriform growth pattern.
Adenoid cystic carcinoma. Immunostaining for p40 decorates the basal cell layer.
Adenoid cystic carcinoma. Low-power view of adenoid cystic carcinoma showing a prevailing cribriform growth pattern.
Adenoid cystic carcinoma. Adenoid cystic carcinoma of the tongue with perineural and intraneural invasion.
Adenoid cystic carcinoma. The cribriform pattern of adenoid cystic carcinoma is one of the most helpful features in the diagnosis. This image shows glycosaminoglycan material creating the Swiss-cheese or telephone-dial appearance. Note the stromal-epithelial clefting.
Adenoid cystic carcinoma. Axial CT demonstrates a destructive mass involving the left palate, with bone remodelling. Although not diagnostic of adenoid cystic carcinoma, it is supportive of a malignant salivary gland neoplasm.
A: adenoid cystic carcinoma; Adenoid cystic carcinoma; adenoid cystic carcinoma

Q: Patients with Adenoid Cystic Carcinoma frequently present with neural symptoms (e.g., pain, numbness) due to the tumor's characteristic propensity for prominent [...].
Adenoid cystic carcinoma. A MYB::NFIB-positive case. The tumour shows prominent perineural and intraneural invasion.
Adenoid cystic carcinoma. Adenoid cystic carcinoma of the tongue with perineural and intraneural invasion.
A: perineural invasion
Q: Adenoid Cystic Carcinoma
- Clinical: Patients with [...] usually present with a slow-growing mass and may have neural symptoms such as pain, numbness, and paraesthesia.
- Micro: [...] is characterized by a cribriform pattern with pseudocysts and a basophilic matrix, and often shows perineural invasion.
- Ancillary: MYB or NFIB rearrangements are common in [...] and can be detected by FISH or other methods.
Reference Gallery:
Adenoid cystic carcinoma. Gross photograph showing a firm, unencapsulated, and infiltrative mass with a greyish-white, homogeneous cut surface in the left parotid gland.
Adenoid cystic carcinoma. Cribriform pattern (MYB::NFIB-positive case). Myoepithelial tumour cells with clear cytoplasm and angular nuclei surround multiple cyst-like areas (pseudocysts) that are contiguous with the stroma of the neoplasm (arrow). A small lumen surrounded by eosinophilic, cuboidal cells (asterisk) indicates a focus of true ductal differentiation.
Adenoid cystic carcinoma, solid pattern (MYB::NFIB-positive case). The solid pattern is characterized by dense cellular tumour nests lacking the pseudocystic spaces observed in the cribriform and tubular patterns.
Adenoid cystic carcinoma, high-grade transformation (MYB::NFIB-positive case). A typical cribriform tumour nest (asterisk) is surrounded by tumour nests best characterized as poorly differentiated adenocarcinoma.
Adenoid cystic carcinoma. A MYB::NFIB-positive case. The tumour shows prominent perineural and intraneural invasion.
Adenoid cystic carcinoma. The FNA smear demonstrates the characteristic discrete spheres and branching tubules of the acellular magenta matrix (Romanowsky–Giemsa stain).
Adenoid cystic carcinoma. Cribriform growth pattern.
Adenoid cystic carcinoma. Immunostaining for p40 decorates the basal cell layer.
Adenoid cystic carcinoma. Low-power view of adenoid cystic carcinoma showing a prevailing cribriform growth pattern.
Adenoid cystic carcinoma. Adenoid cystic carcinoma of the tongue with perineural and intraneural invasion.
Adenoid cystic carcinoma. The cribriform pattern of adenoid cystic carcinoma is one of the most helpful features in the diagnosis. This image shows glycosaminoglycan material creating the Swiss-cheese or telephone-dial appearance. Note the stromal-epithelial clefting.
Adenoid cystic carcinoma. Axial CT demonstrates a destructive mass involving the left palate, with bone remodelling. Although not diagnostic of adenoid cystic carcinoma, it is supportive of a malignant salivary gland neoplasm.
A: adenoid cystic carcinoma; Adenoid cystic carcinoma; adenoid cystic carcinoma

Q: Fine-needle aspiration (FNA) smears of Adenoid Cystic Carcinoma characteristically demonstrate discrete spheres and branching tubules composed of an acellular [...] when evaluated with a Romanowsky-Giemsa stain.
Adenoid cystic carcinoma. The FNA smear demonstrates the characteristic discrete spheres and branching tubules of the acellular magenta matrix (Romanowsky–Giemsa stain).
A: magenta matrix
Q: Adenoid Cystic Carcinoma
- Clinical: Patients with [...] usually present with a slow-growing mass and may have neural symptoms such as pain, numbness, and paraesthesia.
- Micro: [...] is characterized by a cribriform pattern with pseudocysts and a basophilic matrix, and often shows perineural invasion.
- Ancillary: MYB or NFIB rearrangements are common in [...] and can be detected by FISH or other methods.
Reference Gallery:
Adenoid cystic carcinoma. Gross photograph showing a firm, unencapsulated, and infiltrative mass with a greyish-white, homogeneous cut surface in the left parotid gland.
Adenoid cystic carcinoma. Cribriform pattern (MYB::NFIB-positive case). Myoepithelial tumour cells with clear cytoplasm and angular nuclei surround multiple cyst-like areas (pseudocysts) that are contiguous with the stroma of the neoplasm (arrow). A small lumen surrounded by eosinophilic, cuboidal cells (asterisk) indicates a focus of true ductal differentiation.
Adenoid cystic carcinoma, solid pattern (MYB::NFIB-positive case). The solid pattern is characterized by dense cellular tumour nests lacking the pseudocystic spaces observed in the cribriform and tubular patterns.
Adenoid cystic carcinoma, high-grade transformation (MYB::NFIB-positive case). A typical cribriform tumour nest (asterisk) is surrounded by tumour nests best characterized as poorly differentiated adenocarcinoma.
Adenoid cystic carcinoma. A MYB::NFIB-positive case. The tumour shows prominent perineural and intraneural invasion.
Adenoid cystic carcinoma. The FNA smear demonstrates the characteristic discrete spheres and branching tubules of the acellular magenta matrix (Romanowsky–Giemsa stain).
Adenoid cystic carcinoma. Cribriform growth pattern.
Adenoid cystic carcinoma. Immunostaining for p40 decorates the basal cell layer.
Adenoid cystic carcinoma. Low-power view of adenoid cystic carcinoma showing a prevailing cribriform growth pattern.
Adenoid cystic carcinoma. Adenoid cystic carcinoma of the tongue with perineural and intraneural invasion.
Adenoid cystic carcinoma. The cribriform pattern of adenoid cystic carcinoma is one of the most helpful features in the diagnosis. This image shows glycosaminoglycan material creating the Swiss-cheese or telephone-dial appearance. Note the stromal-epithelial clefting.
Adenoid cystic carcinoma. Axial CT demonstrates a destructive mass involving the left palate, with bone remodelling. Although not diagnostic of adenoid cystic carcinoma, it is supportive of a malignant salivary gland neoplasm.
A: adenoid cystic carcinoma; Adenoid cystic carcinoma; adenoid cystic carcinoma

Q: Histologically, Basal Cell Adenocarcinoma typically exhibits solid or membranous growth patterns composed of dark cells that demonstrate peripheral [...], often with infiltrative margins into surrounding tissue.
Basal cell adenocarcinoma. The tumour shows infiltration into soft tissue.
Basal cell adenocarcinoma. Most tumours show a solid and/or membranous pattern, although any pattern can be seen.
A: palisading
Back Extra: Basal Cell Adenocarcinoma
- Clinical: Basal Cell Adenocarcinoma (BCAC) typically presents as a slow-growing nodule in the parotid gland, and accounts for < 3% of malignant salivary tumours.
- Micro: BCACs exhibit tubulotrabecular, membranous, or solid growth patterns, with peripheral palisading of dark cells and centrally located ducts.
- Ancillary: Nuclear β-catenin immunoexpression is present in a subset of BCACs, and molecular alterations in CYLD or CTNNB1 may be observed.
Reference Gallery:
Basal cell adenocarcinoma. Syndromic setting. The carcinoma (right) is arising in a background of multiple precursor lesions (left). Compared with the precursor lesions, tumour nests are larger and bounded by more profound sclerosis.
Basal cell adenocarcinoma. The tumour shows infiltration into soft tissue.
Basal cell adenocarcinoma. Perineural invasion can be noted.
Basal cell adenocarcinoma. Most tumours show a solid and/or membranous pattern, although any pattern can be seen.
Basal cell adenocarcinoma. Aggressive features such as high cytonuclear grade with mitoses are rare.
Basal cell adenocarcinoma. Aggressive features such as high cytonuclear grade with necrosis are rare.
Basal cell adenocarcinoma. This tumour shows a tan-white homogeneous cut surface and a multinodular pushing border that may be deceptively innocuous.

Q: In the syndromic setting, Basal Cell Adenocarcinoma may arise in a background of precursor lesions and is characteristically associated with molecular alterations in CTNNB1 or the [...] gene.
Basal cell adenocarcinoma. Syndromic setting. The carcinoma (right) is arising in a background of multiple precursor lesions (left). Compared with the precursor lesions, tumour nests are larger and bounded by more profound sclerosis.
A: CYLD
Back Extra: Basal Cell Adenocarcinoma
- Clinical: Basal Cell Adenocarcinoma (BCAC) typically presents as a slow-growing nodule in the parotid gland, and accounts for < 3% of malignant salivary tumours.
- Micro: BCACs exhibit tubulotrabecular, membranous, or solid growth patterns, with peripheral palisading of dark cells and centrally located ducts.
- Ancillary: Nuclear β-catenin immunoexpression is present in a subset of BCACs, and molecular alterations in CYLD or CTNNB1 may be observed.
Reference Gallery:
Basal cell adenocarcinoma. Syndromic setting. The carcinoma (right) is arising in a background of multiple precursor lesions (left). Compared with the precursor lesions, tumour nests are larger and bounded by more profound sclerosis.
Basal cell adenocarcinoma. The tumour shows infiltration into soft tissue.
Basal cell adenocarcinoma. Perineural invasion can be noted.
Basal cell adenocarcinoma. Most tumours show a solid and/or membranous pattern, although any pattern can be seen.
Basal cell adenocarcinoma. Aggressive features such as high cytonuclear grade with mitoses are rare.
Basal cell adenocarcinoma. Aggressive features such as high cytonuclear grade with necrosis are rare.
Basal cell adenocarcinoma. This tumour shows a tan-white homogeneous cut surface and a multinodular pushing border that may be deceptively innocuous.

Q: Macroscopically, Basal Cell Adenocarcinoma often has a deceptively innocuous, multinodular pushing border, but microscopically distinguishes itself from benign adenomas by frank soft tissue infiltration or [...] invasion.
Basal cell adenocarcinoma. Perineural invasion can be noted.
Basal cell adenocarcinoma. This tumour shows a tan-white homogeneous cut surface and a multinodular pushing border that may be deceptively innocuous.
A: perineural
Back Extra: Basal Cell Adenocarcinoma
- Clinical: Basal Cell Adenocarcinoma (BCAC) typically presents as a slow-growing nodule in the parotid gland, and accounts for < 3% of malignant salivary tumours.
- Micro: BCACs exhibit tubulotrabecular, membranous, or solid growth patterns, with peripheral palisading of dark cells and centrally located ducts.
- Ancillary: Nuclear β-catenin immunoexpression is present in a subset of BCACs, and molecular alterations in CYLD or CTNNB1 may be observed.
Reference Gallery:
Basal cell adenocarcinoma. Syndromic setting. The carcinoma (right) is arising in a background of multiple precursor lesions (left). Compared with the precursor lesions, tumour nests are larger and bounded by more profound sclerosis.
Basal cell adenocarcinoma. The tumour shows infiltration into soft tissue.
Basal cell adenocarcinoma. Perineural invasion can be noted.
Basal cell adenocarcinoma. Most tumours show a solid and/or membranous pattern, although any pattern can be seen.
Basal cell adenocarcinoma. Aggressive features such as high cytonuclear grade with mitoses are rare.
Basal cell adenocarcinoma. Aggressive features such as high cytonuclear grade with necrosis are rare.
Basal cell adenocarcinoma. This tumour shows a tan-white homogeneous cut surface and a multinodular pushing border that may be deceptively innocuous.

Q: Patients with Carcinoma ex pleomorphic adenoma classically present with a longstanding painless tumor that undergoes [...], often correlating with destructive mass features on imaging.
Carcinoma ex pleomorphic adenoma. This coronal CT image demonstrates a large destructive soft tissue–density mass in the right parotid gland.
Carcinoma ex pleomorphic adenoma. This axial CT image shows small calcifications within a large destructive right parotid gland tumour.
A: recent rapid progression
Back Extra: Carcinoma ex pleomorphic adenoma
- Clinical: Carcinoma ex pleomorphic adenoma typically presents as a longstanding painless mass with recent rapid progression, and may cause facial nerve palsy, pain, or skin ulceration.
- Micro: In most cases, the carcinoma component constitutes more than 50% of the tumour volume, often showing features of salivary duct carcinoma or myoepithelial carcinoma.
- Ancillary: PLAG1 or HMGA2 rearrangements detected by FISH serve as a marker of pre-existing pleomorphic adenoma and can assist in the diagnosis of carcinoma ex pleomorphic adenoma.
Reference Gallery:
Carcinoma ex pleomorphic adenoma. High-power view of the invasive carcinoma showing the histology of salivary duct carcinoma.
Carcinoma ex pleomorphic adenoma. Macroscopic view showing the invasive carcinoma at the top and a residual well-circumscribed sclerotic pleomorphic adenoma component at the bottom.
Carcinoma ex pleomorphic adenoma. This coronal CT image demonstrates a large destructive soft tissue–density mass in the right parotid gland.
Carcinoma ex pleomorphic adenoma. This axial CT image shows small calcifications within a large destructive right parotid gland tumour.
Carcinoma ex pleomorphic adenoma. Nodules of pleomorphic adenoma with calcifications are noted in the centre of this tumour. The malignant transformation to carcinoma is seen surrounding the tumour.
Carcinoma ex pleomorphic adenoma. The lower half demonstrates the heavy stromal hyalinization within the pleomorphic adenoma with associated calcifications, while the area of myoepithelial carcinoma expands into the adjacent tissues.
Carcinoma ex pleomorphic adenoma. A heavily hyalinized residuum of pleomorphic adenoma is noted. The carcinoma is seen immediately adjacent.
Carcinoma ex pleomorphic adenoma. In many instances, the initial alterations are identified as profoundly pleomorphic epithelial cells within the lumen of ducts in the pleomorphic adenoma. This degree of atypia is beyond that of a benign tumour.

Q: In Carcinoma ex pleomorphic adenoma, the residual benign component typically exhibits extensive [...] and calcifications adjacent to the invasive malignancy.
Carcinoma ex pleomorphic adenoma. The lower half demonstrates the heavy stromal hyalinization within the pleomorphic adenoma with associated calcifications, while the area of myoepithelial carcinoma expands into the adjacent tissues.
Carcinoma ex pleomorphic adenoma. A heavily hyalinized residuum of pleomorphic adenoma is noted. The carcinoma is seen immediately adjacent.
A: stromal hyalinization
Back Extra: Carcinoma ex pleomorphic adenoma
- Clinical: Carcinoma ex pleomorphic adenoma typically presents as a longstanding painless mass with recent rapid progression, and may cause facial nerve palsy, pain, or skin ulceration.
- Micro: In most cases, the carcinoma component constitutes more than 50% of the tumour volume, often showing features of salivary duct carcinoma or myoepithelial carcinoma.
- Ancillary: PLAG1 or HMGA2 rearrangements detected by FISH serve as a marker of pre-existing pleomorphic adenoma and can assist in the diagnosis of carcinoma ex pleomorphic adenoma.
Reference Gallery:
Carcinoma ex pleomorphic adenoma. High-power view of the invasive carcinoma showing the histology of salivary duct carcinoma.
Carcinoma ex pleomorphic adenoma. Macroscopic view showing the invasive carcinoma at the top and a residual well-circumscribed sclerotic pleomorphic adenoma component at the bottom.
Carcinoma ex pleomorphic adenoma. This coronal CT image demonstrates a large destructive soft tissue–density mass in the right parotid gland.
Carcinoma ex pleomorphic adenoma. This axial CT image shows small calcifications within a large destructive right parotid gland tumour.
Carcinoma ex pleomorphic adenoma. Nodules of pleomorphic adenoma with calcifications are noted in the centre of this tumour. The malignant transformation to carcinoma is seen surrounding the tumour.
Carcinoma ex pleomorphic adenoma. The lower half demonstrates the heavy stromal hyalinization within the pleomorphic adenoma with associated calcifications, while the area of myoepithelial carcinoma expands into the adjacent tissues.
Carcinoma ex pleomorphic adenoma. A heavily hyalinized residuum of pleomorphic adenoma is noted. The carcinoma is seen immediately adjacent.
Carcinoma ex pleomorphic adenoma. In many instances, the initial alterations are identified as profoundly pleomorphic epithelial cells within the lumen of ducts in the pleomorphic adenoma. This degree of atypia is beyond that of a benign tumour.

Q: Microscopically, the invasive malignant component of Carcinoma ex pleomorphic adenoma most frequently exhibits high-grade features resembling myoepithelial carcinoma or [...].
Carcinoma ex pleomorphic adenoma. High-power view of the invasive carcinoma showing the histology of salivary duct carcinoma.
A: salivary duct carcinoma
Back Extra: Carcinoma ex pleomorphic adenoma
- Clinical: Carcinoma ex pleomorphic adenoma typically presents as a longstanding painless mass with recent rapid progression, and may cause facial nerve palsy, pain, or skin ulceration.
- Micro: In most cases, the carcinoma component constitutes more than 50% of the tumour volume, often showing features of salivary duct carcinoma or myoepithelial carcinoma.
- Ancillary: PLAG1 or HMGA2 rearrangements detected by FISH serve as a marker of pre-existing pleomorphic adenoma and can assist in the diagnosis of carcinoma ex pleomorphic adenoma.
Reference Gallery:
Carcinoma ex pleomorphic adenoma. High-power view of the invasive carcinoma showing the histology of salivary duct carcinoma.
Carcinoma ex pleomorphic adenoma. Macroscopic view showing the invasive carcinoma at the top and a residual well-circumscribed sclerotic pleomorphic adenoma component at the bottom.
Carcinoma ex pleomorphic adenoma. This coronal CT image demonstrates a large destructive soft tissue–density mass in the right parotid gland.
Carcinoma ex pleomorphic adenoma. This axial CT image shows small calcifications within a large destructive right parotid gland tumour.
Carcinoma ex pleomorphic adenoma. Nodules of pleomorphic adenoma with calcifications are noted in the centre of this tumour. The malignant transformation to carcinoma is seen surrounding the tumour.
Carcinoma ex pleomorphic adenoma. The lower half demonstrates the heavy stromal hyalinization within the pleomorphic adenoma with associated calcifications, while the area of myoepithelial carcinoma expands into the adjacent tissues.
Carcinoma ex pleomorphic adenoma. A heavily hyalinized residuum of pleomorphic adenoma is noted. The carcinoma is seen immediately adjacent.
Carcinoma ex pleomorphic adenoma. In many instances, the initial alterations are identified as profoundly pleomorphic epithelial cells within the lumen of ducts in the pleomorphic adenoma. This degree of atypia is beyond that of a benign tumour.

Q: Microscopically, Carcinosarcoma of the salivary glands is defined by a biphasic proliferation of high-grade carcinomatous elements mixed with high-grade [...] components (e.g., osteoid, chondroid, or spindle cells).
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. Osteoid and chondroid sarcomatous components.
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. The tumour is composed of high-grade adenocarcinomatous and high-grade sarcomatous components.
A: sarcomatous
Back Extra: Carcinosarcoma of the salivary glands
- Clinical: Carcinosarcomas are typically large, rapidly growing, and infiltrative tumours, with a mean age of presentation at 58 years.
- Micro: The tumour is characterized by a combination of high-grade adenocarcinomatous and sarcomatous components, often with a pre-existing pleomorphic adenoma.
- Ancillary: Immunohistochemistry is essential for distinguishing the sarcomatous component, and a subset of cases may harbour PLAG1 or HMGA2 fusions.
Reference Gallery:
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. Undifferentiated and squamous carcinomatous components.
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. Osteoid and chondroid sarcomatous components.
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. The tumour is composed of high-grade adenocarcinomatous and high-grade sarcomatous components.
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. The tumour is composed of spindle-shaped sarcomatous and high-grade adenocarcinomatous structures. There is a hyalinized focus of pre-existing pleomorphic adenoma in the upper-left part of the picture.

Q: Histologic evaluation of Carcinosarcoma of the salivary glands may reveal a hyalinized background focus, indicating that the high-grade malignant tumor arose from a pre-existing [...].
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. The tumour is composed of spindle-shaped sarcomatous and high-grade adenocarcinomatous structures. There is a hyalinized focus of pre-existing pleomorphic adenoma in the upper-left part of the picture.
A: pleomorphic adenoma
Back Extra: Carcinosarcoma of the salivary glands
- Clinical: Carcinosarcomas are typically large, rapidly growing, and infiltrative tumours, with a mean age of presentation at 58 years.
- Micro: The tumour is characterized by a combination of high-grade adenocarcinomatous and sarcomatous components, often with a pre-existing pleomorphic adenoma.
- Ancillary: Immunohistochemistry is essential for distinguishing the sarcomatous component, and a subset of cases may harbour PLAG1 or HMGA2 fusions.
Reference Gallery:
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. Undifferentiated and squamous carcinomatous components.
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. Osteoid and chondroid sarcomatous components.
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. The tumour is composed of high-grade adenocarcinomatous and high-grade sarcomatous components.
Carcinosarcoma ex pleomorphic adenoma of the parotid gland. The tumour is composed of spindle-shaped sarcomatous and high-grade adenocarcinomatous structures. There is a hyalinized focus of pre-existing pleomorphic adenoma in the upper-left part of the picture.

Q: The histologic hallmark of Epithelial-Myoepithelial Carcinoma is the presence of biphasic tubular structures composed of inner eosinophilic ductal cells and outer [...] cells.
Epithelial-myoepithelial carcinoma. Bilayered tubular structures, consisting of inner eosinophilic ductal cells and outer polygonal clear myoepithelial cells.
A: clear myoepithelial
Back Extra: Epithelial-Myoepithelial Carcinoma
- Clinical: Epithelial-Myoepithelial Carcinoma typically presents as a slow-growing, painless mass in the salivary glands, with rare lymphadenopathy.
- Micro: The hallmark of Epithelial-Myoepithelial Carcinoma is the presence of biphasic tubular structures with inner eosinophilic ductal cells and outer clear myoepithelial cells.
- Ancillary: Immunohistochemistry shows luminal cells positive for CK7 and abluminal cells positive for SMA and calponin, with frequent RAS p.Q61R mutations.
Reference Gallery:
Epithelial-myoepithelial carcinoma. Low-power view shows a multinodular growth pattern.
Epithelial-myoepithelial carcinoma. Bilayered tubular structures, consisting of inner eosinophilic ductal cells and outer polygonal clear myoepithelial cells.
Epithelial-myoepithelial carcinoma, histological variations. A cribriform pattern with multiple pseudocysts.
Epithelial-myoepithelial carcinoma, histological variations. Sebaceous differentiation featuring tumour cells with bubbly cytoplasm.
Epithelial-myoepithelial carcinoma, histological variations. Apocrine differentiation of ductal cells.
Epithelial-myoepithelial carcinoma, histological variations. A double-clear tubular pattern. Both inner ductal cells and outer myoepithelial cells exhibit clear cytoplasm.
Epithelial-myoepithelial carcinoma. Immunostaining for CK7 highlights the luminal ductal cells.
Epithelial-myoepithelial carcinoma. The abluminal myoepithelial cells are positive for SMA.
Epithelial-myoepithelial carcinoma. RAS p.Q61R is expressed in the abluminal myoepithelial cells.

Q: To confirm the biphasic population in Epithelial-Myoepithelial Carcinoma, immunohistochemistry typically demonstrates inner luminal cells positive for CK7 and outer abluminal cells positive for [...] and calponin.
Epithelial-myoepithelial carcinoma. Immunostaining for CK7 highlights the luminal ductal cells.
Epithelial-myoepithelial carcinoma. The abluminal myoepithelial cells are positive for SMA.
A: SMA
Back Extra: Epithelial-Myoepithelial Carcinoma
- Clinical: Epithelial-Myoepithelial Carcinoma typically presents as a slow-growing, painless mass in the salivary glands, with rare lymphadenopathy.
- Micro: The hallmark of Epithelial-Myoepithelial Carcinoma is the presence of biphasic tubular structures with inner eosinophilic ductal cells and outer clear myoepithelial cells.
- Ancillary: Immunohistochemistry shows luminal cells positive for CK7 and abluminal cells positive for SMA and calponin, with frequent RAS p.Q61R mutations.
Reference Gallery:
Epithelial-myoepithelial carcinoma. Low-power view shows a multinodular growth pattern.
Epithelial-myoepithelial carcinoma. Bilayered tubular structures, consisting of inner eosinophilic ductal cells and outer polygonal clear myoepithelial cells.
Epithelial-myoepithelial carcinoma, histological variations. A cribriform pattern with multiple pseudocysts.
Epithelial-myoepithelial carcinoma, histological variations. Sebaceous differentiation featuring tumour cells with bubbly cytoplasm.
Epithelial-myoepithelial carcinoma, histological variations. Apocrine differentiation of ductal cells.
Epithelial-myoepithelial carcinoma, histological variations. A double-clear tubular pattern. Both inner ductal cells and outer myoepithelial cells exhibit clear cytoplasm.
Epithelial-myoepithelial carcinoma. Immunostaining for CK7 highlights the luminal ductal cells.
Epithelial-myoepithelial carcinoma. The abluminal myoepithelial cells are positive for SMA.
Epithelial-myoepithelial carcinoma. RAS p.Q61R is expressed in the abluminal myoepithelial cells.

Q: A frequent genetic alteration associated with Epithelial-Myoepithelial Carcinoma is the [...] mutation, which can be highlighted in the abluminal cells by immunohistochemistry.
Epithelial-myoepithelial carcinoma. RAS p.Q61R is expressed in the abluminal myoepithelial cells.
A: RAS p.Q61R
Back Extra: Epithelial-Myoepithelial Carcinoma
- Clinical: Epithelial-Myoepithelial Carcinoma typically presents as a slow-growing, painless mass in the salivary glands, with rare lymphadenopathy.
- Micro: The hallmark of Epithelial-Myoepithelial Carcinoma is the presence of biphasic tubular structures with inner eosinophilic ductal cells and outer clear myoepithelial cells.
- Ancillary: Immunohistochemistry shows luminal cells positive for CK7 and abluminal cells positive for SMA and calponin, with frequent RAS p.Q61R mutations.
Reference Gallery:
Epithelial-myoepithelial carcinoma. Low-power view shows a multinodular growth pattern.
Epithelial-myoepithelial carcinoma. Bilayered tubular structures, consisting of inner eosinophilic ductal cells and outer polygonal clear myoepithelial cells.
Epithelial-myoepithelial carcinoma, histological variations. A cribriform pattern with multiple pseudocysts.
Epithelial-myoepithelial carcinoma, histological variations. Sebaceous differentiation featuring tumour cells with bubbly cytoplasm.
Epithelial-myoepithelial carcinoma, histological variations. Apocrine differentiation of ductal cells.
Epithelial-myoepithelial carcinoma, histological variations. A double-clear tubular pattern. Both inner ductal cells and outer myoepithelial cells exhibit clear cytoplasm.
Epithelial-myoepithelial carcinoma. Immunostaining for CK7 highlights the luminal ductal cells.
Epithelial-myoepithelial carcinoma. The abluminal myoepithelial cells are positive for SMA.
Epithelial-myoepithelial carcinoma. RAS p.Q61R is expressed in the abluminal myoepithelial cells.

Q: Histologically, Hyalinizing Clear Cell Carcinoma is characterized by nests and cords of bland clear to eosinophilic cells embedded in a characteristically [...] stroma.
Hyalinizing clear cell carcinoma. The tumour shows bland clear cells in cords and small nests in a sclerotic stroma.
A: hyalinized
Back Extra: Hyalinizing Clear Cell Carcinoma
- Clinical: Most Hyalinizing Clear Cell Carcinomas (HCCCs) present with localized swelling, and the overlying mucosa may be ulcerated. Pain and cranial nerve involvement are rare.
- Micro: HCCCs show a combination of clear and eosinophilic cells arranged in nests and cords, with a variably hyalinized stroma. Perineural invasion is common.
- Ancillary: HCCC cells are typically positive for p63, high-molecular-weight keratins, and EWSR1 fusion, but negative for myoepithelial markers.
Reference Gallery:
Hyalinizing clear cell carcinoma. The tumour shows a combination of clear and eosinophilic cords of cells with perineural invasion.
Hyalinizing clear cell carcinoma. The tumour shows bland clear cells in cords and small nests in a sclerotic stroma.
Hyalinizing clear cell carcinoma. The tumour may connect to the surface in the oral cavity and may show pagetoid spread, or pseudoepitheliomatous hyperplasia of the squamous mucosa (shown here).
Hyalinizing clear cell carcinoma. Some hyalinizing clear cell carcinomas have minimal clear cell change. This tumour is mostly eosinophilic, with only a small focus of clear cells.
Hyalinizing clear cell carcinoma. About half of all cases show focal mucin, and occasional cases have conspicuous goblet-type mucinous cells (mucicarmine).
Hyalinizing clear cell carcinoma. The majority of cases stain diffusely with p63.
Hyalinizing clear cell carcinoma. Most hyalinizing clear cell carcinomas stain diffusely with high-molecular-weight keratins. This staining pattern reflects a squamous phenotype and is a pitfall in the differential diagnosis with mucoepidermoid carcinoma.

Q: Immunohistochemically, Hyalinizing Clear Cell Carcinoma typically shows diffuse nuclear positivity for [...], along with expression of high-molecular-weight keratins.
Hyalinizing clear cell carcinoma. The majority of cases stain diffusely with p63.
Hyalinizing clear cell carcinoma. Most hyalinizing clear cell carcinomas stain diffusely with high-molecular-weight keratins. This staining pattern reflects a squamous phenotype and is a pitfall in the differential diagnosis with mucoepidermoid carcinoma.
A: p63
Back Extra: Hyalinizing Clear Cell Carcinoma
- Clinical: Most Hyalinizing Clear Cell Carcinomas (HCCCs) present with localized swelling, and the overlying mucosa may be ulcerated. Pain and cranial nerve involvement are rare.
- Micro: HCCCs show a combination of clear and eosinophilic cells arranged in nests and cords, with a variably hyalinized stroma. Perineural invasion is common.
- Ancillary: HCCC cells are typically positive for p63, high-molecular-weight keratins, and EWSR1 fusion, but negative for myoepithelial markers.
Reference Gallery:
Hyalinizing clear cell carcinoma. The tumour shows a combination of clear and eosinophilic cords of cells with perineural invasion.
Hyalinizing clear cell carcinoma. The tumour shows bland clear cells in cords and small nests in a sclerotic stroma.
Hyalinizing clear cell carcinoma. The tumour may connect to the surface in the oral cavity and may show pagetoid spread, or pseudoepitheliomatous hyperplasia of the squamous mucosa (shown here).
Hyalinizing clear cell carcinoma. Some hyalinizing clear cell carcinomas have minimal clear cell change. This tumour is mostly eosinophilic, with only a small focus of clear cells.
Hyalinizing clear cell carcinoma. About half of all cases show focal mucin, and occasional cases have conspicuous goblet-type mucinous cells (mucicarmine).
Hyalinizing clear cell carcinoma. The majority of cases stain diffusely with p63.
Hyalinizing clear cell carcinoma. Most hyalinizing clear cell carcinomas stain diffusely with high-molecular-weight keratins. This staining pattern reflects a squamous phenotype and is a pitfall in the differential diagnosis with mucoepidermoid carcinoma.

Q: Despite having relatively bland cytologic features, Hyalinizing Clear Cell Carcinoma is a malignant tumor that frequently demonstrates [...].
Hyalinizing clear cell carcinoma. The tumour shows a combination of clear and eosinophilic cords of cells with perineural invasion.
A: perineural invasion
Back Extra: Hyalinizing Clear Cell Carcinoma
- Clinical: Most Hyalinizing Clear Cell Carcinomas (HCCCs) present with localized swelling, and the overlying mucosa may be ulcerated. Pain and cranial nerve involvement are rare.
- Micro: HCCCs show a combination of clear and eosinophilic cells arranged in nests and cords, with a variably hyalinized stroma. Perineural invasion is common.
- Ancillary: HCCC cells are typically positive for p63, high-molecular-weight keratins, and EWSR1 fusion, but negative for myoepithelial markers.
Reference Gallery:
Hyalinizing clear cell carcinoma. The tumour shows a combination of clear and eosinophilic cords of cells with perineural invasion.
Hyalinizing clear cell carcinoma. The tumour shows bland clear cells in cords and small nests in a sclerotic stroma.
Hyalinizing clear cell carcinoma. The tumour may connect to the surface in the oral cavity and may show pagetoid spread, or pseudoepitheliomatous hyperplasia of the squamous mucosa (shown here).
Hyalinizing clear cell carcinoma. Some hyalinizing clear cell carcinomas have minimal clear cell change. This tumour is mostly eosinophilic, with only a small focus of clear cells.
Hyalinizing clear cell carcinoma. About half of all cases show focal mucin, and occasional cases have conspicuous goblet-type mucinous cells (mucicarmine).
Hyalinizing clear cell carcinoma. The majority of cases stain diffusely with p63.
Hyalinizing clear cell carcinoma. Most hyalinizing clear cell carcinomas stain diffusely with high-molecular-weight keratins. This staining pattern reflects a squamous phenotype and is a pitfall in the differential diagnosis with mucoepidermoid carcinoma.

Q: The defining histologic feature of Intraductal Carcinoma is the presence of tumor lobules with solid, cribriform, or micropapillary growth completely surrounded by a continuous layer of [...] cells.
Intraductal carcinoma. Intercalated duct type. All forms of intraductal carcinoma are characterized by a rim of myoepithelial cells completely surrounding the tumour lobules. Here, the myoepithelial cells are highlighted by p40 immunostaining.
Intraductal carcinoma, apocrine subtype. Almost intact abluminal myoepithelial layer decorated by p63 immunostaining.
Intraductal carcinoma. Intercalated duct cell subtype. This intraductal carcinoma has a typical low-power appearance of large cysts and rounded lobules with solid, cribriform, and micropapillary growth. Although cell morphology cannot be seen at this magnification, the blue appearance is in keeping with intercalated duct–type intraductal carcinoma. Haemorrhage and cholesterol clefts are evident. This case harboured NCOA4::RET.
A: myoepithelial
Back Extra: Intraductal Carcinoma
- Clinical: Intraductal carcinoma (IDC) typically presents as a longstanding painless swelling in the salivary gland. Rare cases can progress to invasive carcinoma ex IDC.
- Micro: IDCs are characterized by rounded cysts and lobules with solid, cribriform, and micropapillary growth patterns, all surrounded by a continuous layer of myoepithelial cells. Apocrine IDCs show large cells with bubbly eosinophilic cytoplasm and snouting.
- Ancillary: Intercalated duct and oncocytic IDCs are positive for S100, SOX10, and mammaglobin but negative for AR and GCDFP-15. Apocrine IDC is positive for AR. Myoepithelial cells are consistently positive for p40/p63, CK14, SMA, and calponin.
Reference Gallery:
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. Two different morphologies can be seen in this mixed intraductal carcinoma. Apocrine cells (top) have eosinophilic cytoplasm, apical snouting, and large nucleoli. Intercalated duct cells (bottom) have less cytoplasm, which is more amphophilic; smaller nuclei; and indistinct nucleoli. The nests of both components are rimmed by a subtle layer of flattened myoepithelial cells. This case harboured TRIM27::RET.
Intraductal carcinoma, oncocytic subtype. This case consists of tightly packed, solid nests of oncocytic cells with abundant granular eosinophilic cytoplasm and round nuclei with small, distinct nucleoli. This tumour was positive for S100 and negative for AR (not shown), and it harboured BRAF p.V600E.
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. S100 is diffusely positive in the intercalated duct component (bottom), whereas in the apocrine component (top) only the surrounding myoepithelial cells stain.
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. Only the apocrine tumour component (top) of this mixed intraductal carcinoma was positive for AR.
Intraductal carcinoma. Intercalated duct type. All forms of intraductal carcinoma are characterized by a rim of myoepithelial cells completely surrounding the tumour lobules. Here, the myoepithelial cells are highlighted by p40 immunostaining.
Intraductal carcinoma, apocrine subtype. Intraductal papillary proliferations with widespread apocrine differentiation.
Intraductal carcinoma, apocrine subtype. The tumour cells are positive for AR.
Intraductal carcinoma, apocrine subtype. Almost intact abluminal myoepithelial layer decorated by p63 immunostaining.
Intraductal carcinoma. Intercalated duct cell subtype. This intraductal carcinoma has a typical low-power appearance of large cysts and rounded lobules with solid, cribriform, and micropapillary growth. Although cell morphology cannot be seen at this magnification, the blue appearance is in keeping with intercalated duct–type intraductal carcinoma. Haemorrhage and cholesterol clefts are evident. This case harboured NCOA4::RET.

Q: The apocrine subtype of Intraductal Carcinoma is typically positive for [...], distinguishing it from the intercalated duct and oncocytic subtypes.
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. Only the apocrine tumour component (top) of this mixed intraductal carcinoma was positive for AR.
Intraductal carcinoma, apocrine subtype. The tumour cells are positive for AR.
A: androgen receptor (AR)
Back Extra: Intraductal Carcinoma
- Clinical: Intraductal carcinoma (IDC) typically presents as a longstanding painless swelling in the salivary gland. Rare cases can progress to invasive carcinoma ex IDC.
- Micro: IDCs are characterized by rounded cysts and lobules with solid, cribriform, and micropapillary growth patterns, all surrounded by a continuous layer of myoepithelial cells. Apocrine IDCs show large cells with bubbly eosinophilic cytoplasm and snouting.
- Ancillary: Intercalated duct and oncocytic IDCs are positive for S100, SOX10, and mammaglobin but negative for AR and GCDFP-15. Apocrine IDC is positive for AR. Myoepithelial cells are consistently positive for p40/p63, CK14, SMA, and calponin.
Reference Gallery:
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. Two different morphologies can be seen in this mixed intraductal carcinoma. Apocrine cells (top) have eosinophilic cytoplasm, apical snouting, and large nucleoli. Intercalated duct cells (bottom) have less cytoplasm, which is more amphophilic; smaller nuclei; and indistinct nucleoli. The nests of both components are rimmed by a subtle layer of flattened myoepithelial cells. This case harboured TRIM27::RET.
Intraductal carcinoma, oncocytic subtype. This case consists of tightly packed, solid nests of oncocytic cells with abundant granular eosinophilic cytoplasm and round nuclei with small, distinct nucleoli. This tumour was positive for S100 and negative for AR (not shown), and it harboured BRAF p.V600E.
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. S100 is diffusely positive in the intercalated duct component (bottom), whereas in the apocrine component (top) only the surrounding myoepithelial cells stain.
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. Only the apocrine tumour component (top) of this mixed intraductal carcinoma was positive for AR.
Intraductal carcinoma. Intercalated duct type. All forms of intraductal carcinoma are characterized by a rim of myoepithelial cells completely surrounding the tumour lobules. Here, the myoepithelial cells are highlighted by p40 immunostaining.
Intraductal carcinoma, apocrine subtype. Intraductal papillary proliferations with widespread apocrine differentiation.
Intraductal carcinoma, apocrine subtype. The tumour cells are positive for AR.
Intraductal carcinoma, apocrine subtype. Almost intact abluminal myoepithelial layer decorated by p63 immunostaining.
Intraductal carcinoma. Intercalated duct cell subtype. This intraductal carcinoma has a typical low-power appearance of large cysts and rounded lobules with solid, cribriform, and micropapillary growth. Although cell morphology cannot be seen at this magnification, the blue appearance is in keeping with intercalated duct–type intraductal carcinoma. Haemorrhage and cholesterol clefts are evident. This case harboured NCOA4::RET.

Q: In Intraductal Carcinoma, the intercalated duct and oncocytic subtypes are characteristically positive for [...], SOX10, and mammaglobin, whereas the apocrine subtype is typically negative.
Intraductal carcinoma, oncocytic subtype. This case consists of tightly packed, solid nests of oncocytic cells with abundant granular eosinophilic cytoplasm and round nuclei with small, distinct nucleoli. This tumour was positive for S100 and negative for AR (not shown), and it harboured BRAF p.V600E.
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. S100 is diffusely positive in the intercalated duct component (bottom), whereas in the apocrine component (top) only the surrounding myoepithelial cells stain.
A: S100
Back Extra: Intraductal Carcinoma
- Clinical: Intraductal carcinoma (IDC) typically presents as a longstanding painless swelling in the salivary gland. Rare cases can progress to invasive carcinoma ex IDC.
- Micro: IDCs are characterized by rounded cysts and lobules with solid, cribriform, and micropapillary growth patterns, all surrounded by a continuous layer of myoepithelial cells. Apocrine IDCs show large cells with bubbly eosinophilic cytoplasm and snouting.
- Ancillary: Intercalated duct and oncocytic IDCs are positive for S100, SOX10, and mammaglobin but negative for AR and GCDFP-15. Apocrine IDC is positive for AR. Myoepithelial cells are consistently positive for p40/p63, CK14, SMA, and calponin.
Reference Gallery:
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. Two different morphologies can be seen in this mixed intraductal carcinoma. Apocrine cells (top) have eosinophilic cytoplasm, apical snouting, and large nucleoli. Intercalated duct cells (bottom) have less cytoplasm, which is more amphophilic; smaller nuclei; and indistinct nucleoli. The nests of both components are rimmed by a subtle layer of flattened myoepithelial cells. This case harboured TRIM27::RET.
Intraductal carcinoma, oncocytic subtype. This case consists of tightly packed, solid nests of oncocytic cells with abundant granular eosinophilic cytoplasm and round nuclei with small, distinct nucleoli. This tumour was positive for S100 and negative for AR (not shown), and it harboured BRAF p.V600E.
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. S100 is diffusely positive in the intercalated duct component (bottom), whereas in the apocrine component (top) only the surrounding myoepithelial cells stain.
Intraductal carcinoma, mixed intercalated duct–apocrine subtype. Only the apocrine tumour component (top) of this mixed intraductal carcinoma was positive for AR.
Intraductal carcinoma. Intercalated duct type. All forms of intraductal carcinoma are characterized by a rim of myoepithelial cells completely surrounding the tumour lobules. Here, the myoepithelial cells are highlighted by p40 immunostaining.
Intraductal carcinoma, apocrine subtype. Intraductal papillary proliferations with widespread apocrine differentiation.
Intraductal carcinoma, apocrine subtype. The tumour cells are positive for AR.
Intraductal carcinoma, apocrine subtype. Almost intact abluminal myoepithelial layer decorated by p63 immunostaining.
Intraductal carcinoma. Intercalated duct cell subtype. This intraductal carcinoma has a typical low-power appearance of large cysts and rounded lobules with solid, cribriform, and micropapillary growth. Although cell morphology cannot be seen at this magnification, the blue appearance is in keeping with intercalated duct–type intraductal carcinoma. Haemorrhage and cholesterol clefts are evident. This case harboured NCOA4::RET.

Q: Microscopic evaluation of Lymphoepithelial Carcinoma reveals nests of large, anaplastic carcinoma cells with prominent nucleoli arranged in a [...] pattern within a dense lymphoid stroma.
Salivary lymphoepithelial carcinoma. Low-power view demonstrates adjacent salivary gland tissue next to a nested to sheet-like infiltrate of neoplastic epithelial cells in a background lymphoid stroma.
Salivary lymphoepithelial carcinoma. The neoplastic cells are arranged in a syncytium, showing large round nuclei with prominent nucleoli and nuclear chromatin clearing.
A: syncytial
Back Extra: Lymphoepithelial Carcinoma
- Clinical: Patients typically present with a painless mass; pain and nerve findings are rare. Cervical lymphadenopathy is noted in about 17% of cases, and EBV infection is commonly associated.
- Micro: The histological features include nests of large anaplastic carcinoma cells within a lymphoid stroma, often showing a syncytial arrangement and prominent nucleoli.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is essential for establishing the presence of EBV, a key diagnostic marker.
Reference Gallery:
Salivary lymphoepithelial carcinoma. Low-power view demonstrates adjacent salivary gland tissue next to a nested to sheet-like infiltrate of neoplastic epithelial cells in a background lymphoid stroma.
Salivary lymphoepithelial carcinoma. The almost-1:1 ratio of neoplastic epithelial cells to lymphoid cells may make identification of the neoplastic elements challenging. Isolated multinucleated tumour giant cells are seen.
Salivary lymphoepithelial carcinoma. The neoplastic cells are arranged in a syncytium, showing large round nuclei with prominent nucleoli and nuclear chromatin clearing.
Salivary lymphoepithelial carcinoma. Tumour cell spindling may occasionally be the dominant finding in lymphoepithelial carcinomas.
Salivary lymphoepithelial carcinoma. The neoplastic cells show a sieve- or lace-like pancytokeratin immunoreactivity, a result of the adjacent lymphoid elements compressing the cytoplasm (AE1/AE3).
Salivary lymphoepithelial carcinoma. All of the neoplastic cell nuclei demonstrate a strong and diffuse reaction for EBER in situ hybridization, a characteristic finding of this neoplasm.
Lymphoepithelial carcinoma. The fish-flesh cut appearance is quite characteristic of lymphoepithelial carcinoma in the salivary glands.

Q: Diagnosing Lymphoepithelial Carcinoma frequently requires in situ hybridization for [...], confirming the neoplasm's strong association with the Epstein-Barr virus (EBV).
Salivary lymphoepithelial carcinoma. All of the neoplastic cell nuclei demonstrate a strong and diffuse reaction for EBER in situ hybridization, a characteristic finding of this neoplasm.
A: EBER
Back Extra: Lymphoepithelial Carcinoma
- Clinical: Patients typically present with a painless mass; pain and nerve findings are rare. Cervical lymphadenopathy is noted in about 17% of cases, and EBV infection is commonly associated.
- Micro: The histological features include nests of large anaplastic carcinoma cells within a lymphoid stroma, often showing a syncytial arrangement and prominent nucleoli.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is essential for establishing the presence of EBV, a key diagnostic marker.
Reference Gallery:
Salivary lymphoepithelial carcinoma. Low-power view demonstrates adjacent salivary gland tissue next to a nested to sheet-like infiltrate of neoplastic epithelial cells in a background lymphoid stroma.
Salivary lymphoepithelial carcinoma. The almost-1:1 ratio of neoplastic epithelial cells to lymphoid cells may make identification of the neoplastic elements challenging. Isolated multinucleated tumour giant cells are seen.
Salivary lymphoepithelial carcinoma. The neoplastic cells are arranged in a syncytium, showing large round nuclei with prominent nucleoli and nuclear chromatin clearing.
Salivary lymphoepithelial carcinoma. Tumour cell spindling may occasionally be the dominant finding in lymphoepithelial carcinomas.
Salivary lymphoepithelial carcinoma. The neoplastic cells show a sieve- or lace-like pancytokeratin immunoreactivity, a result of the adjacent lymphoid elements compressing the cytoplasm (AE1/AE3).
Salivary lymphoepithelial carcinoma. All of the neoplastic cell nuclei demonstrate a strong and diffuse reaction for EBER in situ hybridization, a characteristic finding of this neoplasm.
Lymphoepithelial carcinoma. The fish-flesh cut appearance is quite characteristic of lymphoepithelial carcinoma in the salivary glands.

Q: Grossly, the cut surface of a salivary gland Lymphoepithelial Carcinoma typically displays a characteristic [...] appearance.
Lymphoepithelial carcinoma. The fish-flesh cut appearance is quite characteristic of lymphoepithelial carcinoma in the salivary glands.
A: fish-flesh
Back Extra: Lymphoepithelial Carcinoma
- Clinical: Patients typically present with a painless mass; pain and nerve findings are rare. Cervical lymphadenopathy is noted in about 17% of cases, and EBV infection is commonly associated.
- Micro: The histological features include nests of large anaplastic carcinoma cells within a lymphoid stroma, often showing a syncytial arrangement and prominent nucleoli.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is essential for establishing the presence of EBV, a key diagnostic marker.
Reference Gallery:
Salivary lymphoepithelial carcinoma. Low-power view demonstrates adjacent salivary gland tissue next to a nested to sheet-like infiltrate of neoplastic epithelial cells in a background lymphoid stroma.
Salivary lymphoepithelial carcinoma. The almost-1:1 ratio of neoplastic epithelial cells to lymphoid cells may make identification of the neoplastic elements challenging. Isolated multinucleated tumour giant cells are seen.
Salivary lymphoepithelial carcinoma. The neoplastic cells are arranged in a syncytium, showing large round nuclei with prominent nucleoli and nuclear chromatin clearing.
Salivary lymphoepithelial carcinoma. Tumour cell spindling may occasionally be the dominant finding in lymphoepithelial carcinomas.
Salivary lymphoepithelial carcinoma. The neoplastic cells show a sieve- or lace-like pancytokeratin immunoreactivity, a result of the adjacent lymphoid elements compressing the cytoplasm (AE1/AE3).
Salivary lymphoepithelial carcinoma. All of the neoplastic cell nuclei demonstrate a strong and diffuse reaction for EBER in situ hybridization, a characteristic finding of this neoplasm.
Lymphoepithelial carcinoma. The fish-flesh cut appearance is quite characteristic of lymphoepithelial carcinoma in the salivary glands.

Q: Histologically, Microsecretory Adenocarcinoma classically features [...] filled with pale, bluish secretions set in a cellular fibromyxoid stroma.
Microsecretory adenocarcinoma. The prototypical appearance of microsecretory adenocarcinoma is microcysts filled with pale, bluish secretions, set in a cellular fibromyxoid stroma.
Microsecretory adenocarcinoma. The tumour cells are flattened, with modest amounts of eosinophilic to clear cytoplasm and monotonous, hyperchromatic oval nuclei.
A: microcysts
Back Extra: Microsecretory Adenocarcinoma
- Clinical: Patients with microsecretory adenocarcinoma typically present with a painless, slow-growing mass.
- Micro: Microsecretory adenocarcinoma features microcysts filled with pale, bluish secretions and a cellular fibromyxoid stroma.
- Ancillary: Microsecretory adenocarcinoma has a consistent immunoprofile, positive for S100, SOX10, and p63, and negative for p40.
Reference Gallery:
Microsecretory adenocarcinoma. The tumour often initially appears circumscribed, but close inspection reveals subtle infiltration into nearby tissues such as skeletal muscle.
Microsecretory adenocarcinoma. The prototypical appearance of microsecretory adenocarcinoma is microcysts filled with pale, bluish secretions, set in a cellular fibromyxoid stroma.
Microsecretory adenocarcinoma. The tumour cells are flattened, with modest amounts of eosinophilic to clear cytoplasm and monotonous, hyperchromatic oval nuclei.
Microsecretory adenocarcinoma. The tumour has a consistent immunoprofile, with strong and diffuse immunoexpression of S100.
Microsecretory adenocarcinoma. Microsecretory adenocarcinoma has a consistent immunoprofile, with strong and diffuse immunoexpression of p63.
Microsecretory adenocarcinoma. The lack of nuclear reactivity for p40, coupled with the strong p63, helps in reaching a diagnosis for this tumour category.

Q: Regarding its immunoprofile, Microsecretory Adenocarcinoma characteristically exhibits a discrepant staining pattern: it is strongly positive for [...] but notably negative for p40.
Microsecretory adenocarcinoma. Microsecretory adenocarcinoma has a consistent immunoprofile, with strong and diffuse immunoexpression of p63.
Microsecretory adenocarcinoma. The lack of nuclear reactivity for p40, coupled with the strong p63, helps in reaching a diagnosis for this tumour category.
A: p63
Back Extra: Microsecretory Adenocarcinoma
- Clinical: Patients with microsecretory adenocarcinoma typically present with a painless, slow-growing mass.
- Micro: Microsecretory adenocarcinoma features microcysts filled with pale, bluish secretions and a cellular fibromyxoid stroma.
- Ancillary: Microsecretory adenocarcinoma has a consistent immunoprofile, positive for S100, SOX10, and p63, and negative for p40.
Reference Gallery:
Microsecretory adenocarcinoma. The tumour often initially appears circumscribed, but close inspection reveals subtle infiltration into nearby tissues such as skeletal muscle.
Microsecretory adenocarcinoma. The prototypical appearance of microsecretory adenocarcinoma is microcysts filled with pale, bluish secretions, set in a cellular fibromyxoid stroma.
Microsecretory adenocarcinoma. The tumour cells are flattened, with modest amounts of eosinophilic to clear cytoplasm and monotonous, hyperchromatic oval nuclei.
Microsecretory adenocarcinoma. The tumour has a consistent immunoprofile, with strong and diffuse immunoexpression of S100.
Microsecretory adenocarcinoma. Microsecretory adenocarcinoma has a consistent immunoprofile, with strong and diffuse immunoexpression of p63.
Microsecretory adenocarcinoma. The lack of nuclear reactivity for p40, coupled with the strong p63, helps in reaching a diagnosis for this tumour category.

Q: Microsecretory Adenocarcinoma consistently demonstrates strong and diffuse immunoexpression of the neural crest markers SOX10 and [...].
Microsecretory adenocarcinoma. The tumour has a consistent immunoprofile, with strong and diffuse immunoexpression of S100.
A: S100
Back Extra: Microsecretory Adenocarcinoma
- Clinical: Patients with microsecretory adenocarcinoma typically present with a painless, slow-growing mass.
- Micro: Microsecretory adenocarcinoma features microcysts filled with pale, bluish secretions and a cellular fibromyxoid stroma.
- Ancillary: Microsecretory adenocarcinoma has a consistent immunoprofile, positive for S100, SOX10, and p63, and negative for p40.
Reference Gallery:
Microsecretory adenocarcinoma. The tumour often initially appears circumscribed, but close inspection reveals subtle infiltration into nearby tissues such as skeletal muscle.
Microsecretory adenocarcinoma. The prototypical appearance of microsecretory adenocarcinoma is microcysts filled with pale, bluish secretions, set in a cellular fibromyxoid stroma.
Microsecretory adenocarcinoma. The tumour cells are flattened, with modest amounts of eosinophilic to clear cytoplasm and monotonous, hyperchromatic oval nuclei.
Microsecretory adenocarcinoma. The tumour has a consistent immunoprofile, with strong and diffuse immunoexpression of S100.
Microsecretory adenocarcinoma. Microsecretory adenocarcinoma has a consistent immunoprofile, with strong and diffuse immunoexpression of p63.
Microsecretory adenocarcinoma. The lack of nuclear reactivity for p40, coupled with the strong p63, helps in reaching a diagnosis for this tumour category.

Q: Mucinous adenocarcinoma is histologically characterized by the abundant production of intracellular and/or extracellular [...], often forming large stromal lakes that suspend clusters of tumor cells.
Mucinous adenocarcinoma. Nests and cords of tumour cells suspended in stromal mucin pools.
Mucinous adenocarcinoma. Nests of tumour cells with prominent mucin vacuoles suspended in lakes of stromal mucin.
A: mucin
Q: Mucinous Adenocarcinoma
- Clinical: Most patients with [...] present with painless masses or swellings. Nodal metastases are occasionally seen at presentation.
- Micro: [...] is defined by abundant intracellular and/or extracellular mucin production, with variable papillary, colloid, or signet-ring architectures.
- Ancillary: [...] is positive for CK7 and negative for CK20, CDX2, p63, p40, TTF1, S100, calponin, SMA, and AR. AKT1 p.E17K mutation can support the diagnosis.
Reference Gallery:
Mucinous adenocarcinoma. Complex mucin-producing papillary fronds projecting into cystic spaces.
Mucinous adenocarcinoma. Nests and cords of tumour cells suspended in stromal mucin pools.
Mucinous adenocarcinoma. Dyscohesive signet-ring cells with prominent intracytoplasmic mucin vacuoles.
Mucinous adenocarcinoma. Mixed papillary fronds and colloid pools.
Mucinous adenocarcinoma. Columnar cells with apical mucin caps forming complex papillary fronds.
Mucinous adenocarcinoma. Nests of tumour cells with prominent mucin vacuoles suspended in lakes of stromal mucin.
A: Mucinous Adenocarcinoma; Mucinous Adenocarcinoma; Mucinous Adenocarcinoma

Q: In addition to papillary and colloid architectures, mucinous adenocarcinoma can demonstrate dyscohesive tumor cells with prominent intracytoplasmic vacuoles that compress the nucleus to the periphery, known as [...] cells.
Mucinous adenocarcinoma. Dyscohesive signet-ring cells with prominent intracytoplasmic mucin vacuoles.
A: signet-ring
Q: Mucinous Adenocarcinoma
- Clinical: Most patients with [...] present with painless masses or swellings. Nodal metastases are occasionally seen at presentation.
- Micro: [...] is defined by abundant intracellular and/or extracellular mucin production, with variable papillary, colloid, or signet-ring architectures.
- Ancillary: [...] is positive for CK7 and negative for CK20, CDX2, p63, p40, TTF1, S100, calponin, SMA, and AR. AKT1 p.E17K mutation can support the diagnosis.
Reference Gallery:
Mucinous adenocarcinoma. Complex mucin-producing papillary fronds projecting into cystic spaces.
Mucinous adenocarcinoma. Nests and cords of tumour cells suspended in stromal mucin pools.
Mucinous adenocarcinoma. Dyscohesive signet-ring cells with prominent intracytoplasmic mucin vacuoles.
Mucinous adenocarcinoma. Mixed papillary fronds and colloid pools.
Mucinous adenocarcinoma. Columnar cells with apical mucin caps forming complex papillary fronds.
Mucinous adenocarcinoma. Nests of tumour cells with prominent mucin vacuoles suspended in lakes of stromal mucin.
A: Mucinous Adenocarcinoma; Mucinous Adenocarcinoma; Mucinous Adenocarcinoma

Q: Complex mucin-producing papillary fronds projecting into cystic spaces, often admixed with colloid pools, are classic histologic findings of [...].
Mucinous adenocarcinoma. Complex mucin-producing papillary fronds projecting into cystic spaces.
Mucinous adenocarcinoma. Mixed papillary fronds and colloid pools.
Mucinous adenocarcinoma. Columnar cells with apical mucin caps forming complex papillary fronds.
A: mucinous adenocarcinoma
Q: Mucinous Adenocarcinoma
- Clinical: Most patients with [...] present with painless masses or swellings. Nodal metastases are occasionally seen at presentation.
- Micro: [...] is defined by abundant intracellular and/or extracellular mucin production, with variable papillary, colloid, or signet-ring architectures.
- Ancillary: [...] is positive for CK7 and negative for CK20, CDX2, p63, p40, TTF1, S100, calponin, SMA, and AR. AKT1 p.E17K mutation can support the diagnosis.
Reference Gallery:
Mucinous adenocarcinoma. Complex mucin-producing papillary fronds projecting into cystic spaces.
Mucinous adenocarcinoma. Nests and cords of tumour cells suspended in stromal mucin pools.
Mucinous adenocarcinoma. Dyscohesive signet-ring cells with prominent intracytoplasmic mucin vacuoles.
Mucinous adenocarcinoma. Mixed papillary fronds and colloid pools.
Mucinous adenocarcinoma. Columnar cells with apical mucin caps forming complex papillary fronds.
Mucinous adenocarcinoma. Nests of tumour cells with prominent mucin vacuoles suspended in lakes of stromal mucin.
A: Mucinous Adenocarcinoma; Mucinous Adenocarcinoma; Mucinous Adenocarcinoma

Q: Histologically, Mucoepidermoid Carcinoma is classically characterized by a triphasic population of intermediate, squamoid, and [...] cells, which frequently form cystic and solid growth patterns.
Mucoepidermoid carcinoma. Low-grade tumour. Cystic spaces are partly lined by mucous cells. Other cell types include intermediate, squamoid, and partly clear cells.
A: mucous
Back Extra: Mucoepidermoid Carcinoma
- Clinical: Mucoepidermoid carcinoma (MEC) typically presents as a firm and fixed tumour, often with a bluish appearance if situated below an intact oral surface epithelium.
- Micro: MEC is characterized by mucous, intermediate, and squamoid cells forming cystic and solid growth patterns. Cystic spaces are lined by mucous cells, and intermediate cells are often the most frequent cell type.
- Ancillary: The CRTC1::MAML2 fusion gene is specific for MEC and is useful in diagnostic workups. Immunohistochemical p63 or p40 expression, in the absence of S100/SOX10 staining, may also help differentiate MEC from other salivary tumours.
Reference Gallery:
Mucoepidermoid carcinoma. Low-grade tumour. Cystic spaces are partly lined by mucous cells. Other cell types include intermediate, squamoid, and partly clear cells.
Mucoepidermoid carcinoma. Clear cell pattern. Tumour cells have largely clear cytoplasm.
Mucoepidermoid carcinoma. Warthin-like pattern. Tumour cells have oncocytoid and mucous features, and form cystic spaces. Tumour areas are surrounded by lymphatic tissue reminiscent of the architecture of Warthin tumour.
Mucoepidermoid carcinoma. Ciliated pattern. Tumour cells lining cystic spaces display luminal cilia.
Mucoepidermoid carcinoma. Smears from the tumour contain malignant cells, indicative of low-grade mucoepidermoid carcinoma (FNAC, parotid gland; Pap).
Mucoepidermoid carcinoma. Intermediate-grade tumour. Largely solid nests of tumour cells with some ductal, mucinous, and oncocytoid features, and tumour necrosis. There is nerve invasion in the adjacent field (not shown).
Mucoepidermoid carcinoma. High-grade tumour. Poorly differentiated high-grade carcinoma with minor amounts of mucinous cells.
Mucoepidermoid carcinoma. Sclerotic pattern. Tumour cells are embedded in a sclerotic collagenous matrix.
Mucoepidermoid carcinoma. Oncocytic pattern. Prominent oncocytoid features and very few hardly visible mucous cells. CRTC1::MAML2 fusion was detected.
Mucoepidermoid carcinoma. There is a very large, destructive parotid gland mass that has thinned the overlying skin.
Mucoepidermoid carcinoma. Axial CT shows a mass within the palate, with areas of cystic change.
Mucoepidermoid carcinoma. T2-weighted coronal MRI shows a hyperintense, large, destructive right parotid gland mass, with significant soft tissue extension.

Q: The specific genetic hallmark for Mucoepidermoid Carcinoma is the [MAML2] fusion gene, which is especially useful in confirming the diagnosis in challenging variants (e.g., those with a predominantly oncocytic pattern).
Mucoepidermoid carcinoma. Oncocytic pattern. Prominent oncocytoid features and very few hardly visible mucous cells. CRTC1::MAML2 fusion was detected.
A: CRTC1
Back Extra: Mucoepidermoid Carcinoma
- Clinical: Mucoepidermoid carcinoma (MEC) typically presents as a firm and fixed tumour, often with a bluish appearance if situated below an intact oral surface epithelium.
- Micro: MEC is characterized by mucous, intermediate, and squamoid cells forming cystic and solid growth patterns. Cystic spaces are lined by mucous cells, and intermediate cells are often the most frequent cell type.
- Ancillary: The CRTC1::MAML2 fusion gene is specific for MEC and is useful in diagnostic workups. Immunohistochemical p63 or p40 expression, in the absence of S100/SOX10 staining, may also help differentiate MEC from other salivary tumours.
Reference Gallery:
Mucoepidermoid carcinoma. Low-grade tumour. Cystic spaces are partly lined by mucous cells. Other cell types include intermediate, squamoid, and partly clear cells.
Mucoepidermoid carcinoma. Clear cell pattern. Tumour cells have largely clear cytoplasm.
Mucoepidermoid carcinoma. Warthin-like pattern. Tumour cells have oncocytoid and mucous features, and form cystic spaces. Tumour areas are surrounded by lymphatic tissue reminiscent of the architecture of Warthin tumour.
Mucoepidermoid carcinoma. Ciliated pattern. Tumour cells lining cystic spaces display luminal cilia.
Mucoepidermoid carcinoma. Smears from the tumour contain malignant cells, indicative of low-grade mucoepidermoid carcinoma (FNAC, parotid gland; Pap).
Mucoepidermoid carcinoma. Intermediate-grade tumour. Largely solid nests of tumour cells with some ductal, mucinous, and oncocytoid features, and tumour necrosis. There is nerve invasion in the adjacent field (not shown).
Mucoepidermoid carcinoma. High-grade tumour. Poorly differentiated high-grade carcinoma with minor amounts of mucinous cells.
Mucoepidermoid carcinoma. Sclerotic pattern. Tumour cells are embedded in a sclerotic collagenous matrix.
Mucoepidermoid carcinoma. Oncocytic pattern. Prominent oncocytoid features and very few hardly visible mucous cells. CRTC1::MAML2 fusion was detected.
Mucoepidermoid carcinoma. There is a very large, destructive parotid gland mass that has thinned the overlying skin.
Mucoepidermoid carcinoma. Axial CT shows a mass within the palate, with areas of cystic change.
Mucoepidermoid carcinoma. T2-weighted coronal MRI shows a hyperintense, large, destructive right parotid gland mass, with significant soft tissue extension.

Q: The characteristic histologic pattern of [...] consists of a multinodular architecture with a zonal arrangement showing a hypercellular peripheral rim surrounding a hypocellular, often myxoid center.
Myoepithelial carcinoma. Lobulated multinodular pattern with a hypercellular periphery and a hypocellular centre.
Myoepithelial carcinoma. Myoepithelial carcinoma of the parotid gland. The tumour has a multinodular architecture divided by fibrous bands. A characteristic feature is a zonal arrangement with a hypercellular peripheral rim surrounding a hypocellular and often myxoid centre.
A: Myoepithelial Carcinoma
Back Extra: Myoepithelial Carcinoma
- Clinical: Patients often present with a painless, rapidly growing mass in the salivary gland, with irregular, lobulated, poorly defined imaging features.
- Micro: The tumor exhibits a multinodular pattern with a hypercellular peripheral rim and a hypocellular, often myxoid center, and may show spindle, epithelioid, plasmacytoid, and clear cell types.
- Ancillary: Myoepithelial carcinoma expresses cytokeratins, SOX10, S100, and myoepithelial markers like SMA, calponin, and p63/p40, and often harbors PLAG1 fusions.
Reference Gallery:
Myoepithelial carcinoma. Lobulated multinodular pattern with a hypercellular periphery and a hypocellular centre.
Myoepithelial carcinoma. Spindle and epithelioid/plasmacytoid myoepithelial cells with a myxoid stroma.
Myoepithelial carcinoma. Myoepithelial carcinoma of the parotid gland. Clear cells represent a prominent component of a subset of myoepithelial carcinomas. Squamous pearls or overt squamous differentiation are present.
Myoepithelial carcinoma. Myoepithelial carcinoma of the parotid gland. The tumour has a multinodular architecture divided by fibrous bands. A characteristic feature is a zonal arrangement with a hypercellular peripheral rim surrounding a hypocellular and often myxoid centre.

Q: In addition to a multinodular architecture, Myoepithelial Carcinoma often displays a variety of cell types within a myxoid stroma, most notably spindle, epithelioid, clear, and [...] cells.
Myoepithelial carcinoma. Spindle and epithelioid/plasmacytoid myoepithelial cells with a myxoid stroma.
Myoepithelial carcinoma. Myoepithelial carcinoma of the parotid gland. Clear cells represent a prominent component of a subset of myoepithelial carcinomas. Squamous pearls or overt squamous differentiation are present.
A: plasmacytoid
Back Extra: Myoepithelial Carcinoma
- Clinical: Patients often present with a painless, rapidly growing mass in the salivary gland, with irregular, lobulated, poorly defined imaging features.
- Micro: The tumor exhibits a multinodular pattern with a hypercellular peripheral rim and a hypocellular, often myxoid center, and may show spindle, epithelioid, plasmacytoid, and clear cell types.
- Ancillary: Myoepithelial carcinoma expresses cytokeratins, SOX10, S100, and myoepithelial markers like SMA, calponin, and p63/p40, and often harbors PLAG1 fusions.
Reference Gallery:
Myoepithelial carcinoma. Lobulated multinodular pattern with a hypercellular periphery and a hypocellular centre.
Myoepithelial carcinoma. Spindle and epithelioid/plasmacytoid myoepithelial cells with a myxoid stroma.
Myoepithelial carcinoma. Myoepithelial carcinoma of the parotid gland. Clear cells represent a prominent component of a subset of myoepithelial carcinomas. Squamous pearls or overt squamous differentiation are present.
Myoepithelial carcinoma. Myoepithelial carcinoma of the parotid gland. The tumour has a multinodular architecture divided by fibrous bands. A characteristic feature is a zonal arrangement with a hypercellular peripheral rim surrounding a hypocellular and often myxoid centre.

Q: The cribriform subtype of Polymorphous Adenocarcinoma is characterized by optically clear nuclei and distinctive papillary and [...] structures.
Polymorphous adenocarcinoma, cribriform subtype. Optical nuclear chromatin clearing is a characteristic finding in this tumour. Note the papillary and glomeruloid architecture.
Polymorphous adenocarcinoma, cribriform subtype. The low-power photomicrograph demonstrates numerous patterns, with easily identified papillary structures and glomeruloid bodies. Fibrous connective tissue stroma is present. The nuclei show open chromatin, even at this magnification.
Polymorphous adenocarcinoma, cribriform subtype. Solid growth pattern and optically clear nuclei reminiscent of papillary thyroid cancer nuclei.
A: glomeruloid
Back Extra: Polymorphous Adenocarcinoma
- Clinical: Polymorphous adenocarcinoma typically presents as a slowly growing, painless mass. Cervical lymph node metastases are more common in the cribriform subtype.
- Micro: The classic subtype shows uniform small oval nuclei with open chromatin, while the cribriform subtype has glomeruloid and papillary structures with clear nuclei.
- Ancillary: Immunohistochemistry shows diffuse positivity for S100 and cytokeratins. PRKD1, PRKD2, or PRKD3 fusions are highly specific for diagnosis.
Reference Gallery:
Polymorphous adenocarcinoma, classic subtype. The tumour cells have uniform small oval nuclei, scant cytoplasm, open chromatin, and inconspicuous nucleoli. Neurotropism is seen.
Polymorphous adenocarcinoma. S100 is diffusely positive in polymorphous adenocarcinoma, regardless of morphological subtype.
Polymorphous adenocarcinoma, cribriform subtype. Glomeruloid structures.
Polymorphous adenocarcinoma, cribriform subtype. Glomeruloid structures.
Polymorphous adenocarcinoma, cribriform subtype. Optical nuclear chromatin clearing is a characteristic finding in this tumour. Note the papillary and glomeruloid architecture.
Polymorphous adenocarcinoma, cribriform subtype. The low-power photomicrograph demonstrates numerous patterns, with easily identified papillary structures and glomeruloid bodies. Fibrous connective tissue stroma is present. The nuclei show open chromatin, even at this magnification.
Polymorphous adenocarcinoma, cribriform subtype. Islands of neoplastic cells are separated by a fibrous connective tissue stroma. The cells show glomeruloid projections into the lumen with clefting artefacts. The nuclei are monotonous.
Polymorphous adenocarcinoma, cribriform subtype. Numerous patterns, with easily identified papillary structures and glomeruloid bodies. The nuclei show open chromatin. Fibrous connective tissue stroma is present.
Polymorphous adenocarcinoma, cribriform subtype. Solid growth pattern and optically clear nuclei reminiscent of papillary thyroid cancer nuclei.
Polymorphous adenocarcinoma, classic subtype. Various patterns, including tubules, trabeculae, microcysts, and cribriform architecture, are seen in a mucoid/myxoid background. The tumour is often arranged in a targetoid or streaming fashion in the periphery or around nerves.

Q: Regardless of the morphological subtype, Polymorphous Adenocarcinoma characteristically shows diffuse immunohistochemical positivity for cytokeratins and [...].
Polymorphous adenocarcinoma. S100 is diffusely positive in polymorphous adenocarcinoma, regardless of morphological subtype.
A: S100
Back Extra: Polymorphous Adenocarcinoma
- Clinical: Polymorphous adenocarcinoma typically presents as a slowly growing, painless mass. Cervical lymph node metastases are more common in the cribriform subtype.
- Micro: The classic subtype shows uniform small oval nuclei with open chromatin, while the cribriform subtype has glomeruloid and papillary structures with clear nuclei.
- Ancillary: Immunohistochemistry shows diffuse positivity for S100 and cytokeratins. PRKD1, PRKD2, or PRKD3 fusions are highly specific for diagnosis.
Reference Gallery:
Polymorphous adenocarcinoma, classic subtype. The tumour cells have uniform small oval nuclei, scant cytoplasm, open chromatin, and inconspicuous nucleoli. Neurotropism is seen.
Polymorphous adenocarcinoma. S100 is diffusely positive in polymorphous adenocarcinoma, regardless of morphological subtype.
Polymorphous adenocarcinoma, cribriform subtype. Glomeruloid structures.
Polymorphous adenocarcinoma, cribriform subtype. Glomeruloid structures.
Polymorphous adenocarcinoma, cribriform subtype. Optical nuclear chromatin clearing is a characteristic finding in this tumour. Note the papillary and glomeruloid architecture.
Polymorphous adenocarcinoma, cribriform subtype. The low-power photomicrograph demonstrates numerous patterns, with easily identified papillary structures and glomeruloid bodies. Fibrous connective tissue stroma is present. The nuclei show open chromatin, even at this magnification.
Polymorphous adenocarcinoma, cribriform subtype. Islands of neoplastic cells are separated by a fibrous connective tissue stroma. The cells show glomeruloid projections into the lumen with clefting artefacts. The nuclei are monotonous.
Polymorphous adenocarcinoma, cribriform subtype. Numerous patterns, with easily identified papillary structures and glomeruloid bodies. The nuclei show open chromatin. Fibrous connective tissue stroma is present.
Polymorphous adenocarcinoma, cribriform subtype. Solid growth pattern and optically clear nuclei reminiscent of papillary thyroid cancer nuclei.
Polymorphous adenocarcinoma, classic subtype. Various patterns, including tubules, trabeculae, microcysts, and cribriform architecture, are seen in a mucoid/myxoid background. The tumour is often arranged in a targetoid or streaming fashion in the periphery or around nerves.

Q: In the classic subtype of Polymorphous Adenocarcinoma, uniform tumor cells often arrange in a streaming or targetoid fashion around nerves, a characteristic feature known as [...].
Polymorphous adenocarcinoma, classic subtype. The tumour cells have uniform small oval nuclei, scant cytoplasm, open chromatin, and inconspicuous nucleoli. Neurotropism is seen.
Polymorphous adenocarcinoma, classic subtype. Various patterns, including tubules, trabeculae, microcysts, and cribriform architecture, are seen in a mucoid/myxoid background. The tumour is often arranged in a targetoid or streaming fashion in the periphery or around nerves.
A: neurotropism
Back Extra: Polymorphous Adenocarcinoma
- Clinical: Polymorphous adenocarcinoma typically presents as a slowly growing, painless mass. Cervical lymph node metastases are more common in the cribriform subtype.
- Micro: The classic subtype shows uniform small oval nuclei with open chromatin, while the cribriform subtype has glomeruloid and papillary structures with clear nuclei.
- Ancillary: Immunohistochemistry shows diffuse positivity for S100 and cytokeratins. PRKD1, PRKD2, or PRKD3 fusions are highly specific for diagnosis.
Reference Gallery:
Polymorphous adenocarcinoma, classic subtype. The tumour cells have uniform small oval nuclei, scant cytoplasm, open chromatin, and inconspicuous nucleoli. Neurotropism is seen.
Polymorphous adenocarcinoma. S100 is diffusely positive in polymorphous adenocarcinoma, regardless of morphological subtype.
Polymorphous adenocarcinoma, cribriform subtype. Glomeruloid structures.
Polymorphous adenocarcinoma, cribriform subtype. Glomeruloid structures.
Polymorphous adenocarcinoma, cribriform subtype. Optical nuclear chromatin clearing is a characteristic finding in this tumour. Note the papillary and glomeruloid architecture.
Polymorphous adenocarcinoma, cribriform subtype. The low-power photomicrograph demonstrates numerous patterns, with easily identified papillary structures and glomeruloid bodies. Fibrous connective tissue stroma is present. The nuclei show open chromatin, even at this magnification.
Polymorphous adenocarcinoma, cribriform subtype. Islands of neoplastic cells are separated by a fibrous connective tissue stroma. The cells show glomeruloid projections into the lumen with clefting artefacts. The nuclei are monotonous.
Polymorphous adenocarcinoma, cribriform subtype. Numerous patterns, with easily identified papillary structures and glomeruloid bodies. The nuclei show open chromatin. Fibrous connective tissue stroma is present.
Polymorphous adenocarcinoma, cribriform subtype. Solid growth pattern and optically clear nuclei reminiscent of papillary thyroid cancer nuclei.
Polymorphous adenocarcinoma, classic subtype. Various patterns, including tubules, trabeculae, microcysts, and cribriform architecture, are seen in a mucoid/myxoid background. The tumour is often arranged in a targetoid or streaming fashion in the periphery or around nerves.

Q: Histologically, Salivary Duct Carcinoma features a complex architecture including solid, cribriform, and papillary-cystic patterns, frequently accompanied by central [...].
Salivary duct carcinoma. Invasive component of a salivary duct carcinoma comprising glands and solid nests, necrotic areas, and hypocellular hyalinized stroma of probably pre-existing pleomorphic adenoma (lower part of the image).
Salivary duct carcinoma. Complex architecture with cribriforming glands and a Roman-bridge pattern.
A: comedonecrosis
Back Extra: Salivary Duct Carcinoma
- Clinical: Salivary duct carcinoma (SDC) often presents as a rapidly growing mass with symptoms such as facial nerve palsy, pain, and cervical lymphadenopathy.
- Micro: SDCs exhibit a complex architecture with solid, cribriform, and papillary-cystic patterns, frequent comedonecrosis, and large pleomorphic nuclei with prominent nucleoli.
- Ancillary: Approximately 90% of SDCs show moderate to strong immunopositivity for androgen receptor (AR).
Reference Gallery:
Salivary duct carcinoma ex pleomorphic adenoma. Gross presentation of salivary duct carcinoma ex pleomorphic adenoma. Irregular tan-white mass involves the parotid gland (right) and extends to the skin. In the centre of the mass, there is a rounded focus of pre-existing hyalinized pleomorphic adenoma.
Salivary duct carcinoma. Invasive component of a salivary duct carcinoma comprising glands and solid nests, necrotic areas, and hypocellular hyalinized stroma of probably pre-existing pleomorphic adenoma (lower part of the image).
Salivary duct carcinoma. Salivary duct carcinoma cells (oncocytic subtype) characterized by abundant eosinophilic cytoplasm with apocrine-type secretions and enlarged pleomorphic nuclei with prominent nucleoli.
Salivary duct carcinoma. Complex architecture with cribriforming glands and a Roman-bridge pattern.
Salivary duct carcinoma. Moderate to strong immunopositivity for AR.
Salivary duct carcinoma. Sarcomatoid subtype. Conventional salivary duct carcinoma (left) is adjacent to sarcomatoid atypical spindle cells (right).
Salivary duct carcinoma. Mucin-rich subtype. Mucin lakes and cells of conventional salivary duct carcinoma.
Salivary duct carcinoma. Micropapillary subtype. Small clusters of tumour cells, devoid of fibrovascular cores, surrounded by clear spaces.
Salivary duct carcinoma. Axial combined PET-CT shows an infiltrative mass with avid FDG uptake arising from the submandibular gland.
Left parotid salivary duct carcinoma. T1-weighted axial MRI showing intermediate signal lesion spanning superficial and deep lobes.
Left parotid salivary duct carcinoma. Postcontrast fat-suppressed T1-weighted axial MRI showing heterogeneous enhancement.
Left parotid salivary duct carcinoma. T2-weighted axial MRI showing intermediate to low signal intensity (compare with hyperintense pleomorphic adenoma).

Q: In terms of ancillary studies, approximately 90% of Salivary Duct Carcinoma cases demonstrate moderate to strong immunohistochemical positivity for [...].
Salivary duct carcinoma. Moderate to strong immunopositivity for AR.
A: androgen receptor (AR)
Back Extra: Salivary Duct Carcinoma
- Clinical: Salivary duct carcinoma (SDC) often presents as a rapidly growing mass with symptoms such as facial nerve palsy, pain, and cervical lymphadenopathy.
- Micro: SDCs exhibit a complex architecture with solid, cribriform, and papillary-cystic patterns, frequent comedonecrosis, and large pleomorphic nuclei with prominent nucleoli.
- Ancillary: Approximately 90% of SDCs show moderate to strong immunopositivity for androgen receptor (AR).
Reference Gallery:
Salivary duct carcinoma ex pleomorphic adenoma. Gross presentation of salivary duct carcinoma ex pleomorphic adenoma. Irregular tan-white mass involves the parotid gland (right) and extends to the skin. In the centre of the mass, there is a rounded focus of pre-existing hyalinized pleomorphic adenoma.
Salivary duct carcinoma. Invasive component of a salivary duct carcinoma comprising glands and solid nests, necrotic areas, and hypocellular hyalinized stroma of probably pre-existing pleomorphic adenoma (lower part of the image).
Salivary duct carcinoma. Salivary duct carcinoma cells (oncocytic subtype) characterized by abundant eosinophilic cytoplasm with apocrine-type secretions and enlarged pleomorphic nuclei with prominent nucleoli.
Salivary duct carcinoma. Complex architecture with cribriforming glands and a Roman-bridge pattern.
Salivary duct carcinoma. Moderate to strong immunopositivity for AR.
Salivary duct carcinoma. Sarcomatoid subtype. Conventional salivary duct carcinoma (left) is adjacent to sarcomatoid atypical spindle cells (right).
Salivary duct carcinoma. Mucin-rich subtype. Mucin lakes and cells of conventional salivary duct carcinoma.
Salivary duct carcinoma. Micropapillary subtype. Small clusters of tumour cells, devoid of fibrovascular cores, surrounded by clear spaces.
Salivary duct carcinoma. Axial combined PET-CT shows an infiltrative mass with avid FDG uptake arising from the submandibular gland.
Left parotid salivary duct carcinoma. T1-weighted axial MRI showing intermediate signal lesion spanning superficial and deep lobes.
Left parotid salivary duct carcinoma. Postcontrast fat-suppressed T1-weighted axial MRI showing heterogeneous enhancement.
Left parotid salivary duct carcinoma. T2-weighted axial MRI showing intermediate to low signal intensity (compare with hyperintense pleomorphic adenoma).

Q: Microscopically, [...] is characterized by a wide range of infiltrative ductal or glandular proliferation patterns (e.g., solid nests, cords, and cribriform structures) that lack specific diagnostic fusions and fail to conform to any recognized specific tumor category.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, low-grade. This oral cavity tumour was made up of solid nests punctuated by ducts lined by monotonous round nuclei. It does not conform to any known tumour type and was negative for fusions by RNA sequencing.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, intermediate-grade. This submandibular gland tumour consisted of one cell type with monotonous dark nuclei, arranged as infiltrative solid and cribriform nests, cords, and ducts in a myxoid stroma. The tumour was negative for fusions by RNA sequencing.
A: Salivary gland carcinoma NOS
Back Extra: Salivary gland carcinoma NOS
- Clinical: Patients with salivary gland carcinoma NOS typically present with asymptomatic, solitary, firm or cystic masses, which may be painful and can ulcerate in the palate.
- Micro: Tumours display a wide range of ductal or glandular proliferation patterns, with architectural growth including small nests, cords, large islands, and a densely cellular stroma.
- Ancillary: Immunohistochemistry helps distinguish salivary gland carcinoma NOS from other salivary gland tumours and metastatic adenocarcinoma using markers like NR4A3, DOG1, calponin, CK5/6, and p63.
Reference Gallery:
Salivary gland carcinoma NOS. Adenocarcinoma NOS ex intraductal carcinoma. Adjacent to an intercalated duct–type intraductal carcinoma (left), there is a frankly infiltrative tumour (right) comprising irregular glands and micropapillae. Both components harboured NCOA4::RET.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, low-grade. This oral cavity tumour was made up of solid nests punctuated by ducts lined by monotonous round nuclei. It does not conform to any known tumour type and was negative for fusions by RNA sequencing.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, intermediate-grade. This submandibular gland tumour consisted of one cell type with monotonous dark nuclei, arranged as infiltrative solid and cribriform nests, cords, and ducts in a myxoid stroma. The tumour was negative for fusions by RNA sequencing.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, high-grade. This submandibular gland tumour has irregular ducts lined by pleomorphic cells with necrosis and a high mitotic rate. There are no overtly apocrine features, and AR (not shown) was negative.

Q: High-grade cases of [...] display irregular ducts lined by pleomorphic cells, prominent necrosis, and a high mitotic rate, but importantly lack defining features of other specific entities (such as overt apocrine features or androgen receptor expression).
Salivary gland carcinoma NOS. Adenocarcinoma NOS, high-grade. This submandibular gland tumour has irregular ducts lined by pleomorphic cells with necrosis and a high mitotic rate. There are no overtly apocrine features, and AR (not shown) was negative.
A: Salivary gland carcinoma NOS
Back Extra: Salivary gland carcinoma NOS
- Clinical: Patients with salivary gland carcinoma NOS typically present with asymptomatic, solitary, firm or cystic masses, which may be painful and can ulcerate in the palate.
- Micro: Tumours display a wide range of ductal or glandular proliferation patterns, with architectural growth including small nests, cords, large islands, and a densely cellular stroma.
- Ancillary: Immunohistochemistry helps distinguish salivary gland carcinoma NOS from other salivary gland tumours and metastatic adenocarcinoma using markers like NR4A3, DOG1, calponin, CK5/6, and p63.
Reference Gallery:
Salivary gland carcinoma NOS. Adenocarcinoma NOS ex intraductal carcinoma. Adjacent to an intercalated duct–type intraductal carcinoma (left), there is a frankly infiltrative tumour (right) comprising irregular glands and micropapillae. Both components harboured NCOA4::RET.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, low-grade. This oral cavity tumour was made up of solid nests punctuated by ducts lined by monotonous round nuclei. It does not conform to any known tumour type and was negative for fusions by RNA sequencing.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, intermediate-grade. This submandibular gland tumour consisted of one cell type with monotonous dark nuclei, arranged as infiltrative solid and cribriform nests, cords, and ducts in a myxoid stroma. The tumour was negative for fusions by RNA sequencing.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, high-grade. This submandibular gland tumour has irregular ducts lined by pleomorphic cells with necrosis and a high mitotic rate. There are no overtly apocrine features, and AR (not shown) was negative.

Q: In rare instances, [...] can arise ex intraductal carcinoma, displaying an adjacent, frankly infiltrative tumor component comprised of irregular glands and micropapillae.
Salivary gland carcinoma NOS. Adenocarcinoma NOS ex intraductal carcinoma. Adjacent to an intercalated duct–type intraductal carcinoma (left), there is a frankly infiltrative tumour (right) comprising irregular glands and micropapillae. Both components harboured NCOA4::RET.
A: Salivary gland carcinoma NOS
Back Extra: Salivary gland carcinoma NOS
- Clinical: Patients with salivary gland carcinoma NOS typically present with asymptomatic, solitary, firm or cystic masses, which may be painful and can ulcerate in the palate.
- Micro: Tumours display a wide range of ductal or glandular proliferation patterns, with architectural growth including small nests, cords, large islands, and a densely cellular stroma.
- Ancillary: Immunohistochemistry helps distinguish salivary gland carcinoma NOS from other salivary gland tumours and metastatic adenocarcinoma using markers like NR4A3, DOG1, calponin, CK5/6, and p63.
Reference Gallery:
Salivary gland carcinoma NOS. Adenocarcinoma NOS ex intraductal carcinoma. Adjacent to an intercalated duct–type intraductal carcinoma (left), there is a frankly infiltrative tumour (right) comprising irregular glands and micropapillae. Both components harboured NCOA4::RET.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, low-grade. This oral cavity tumour was made up of solid nests punctuated by ducts lined by monotonous round nuclei. It does not conform to any known tumour type and was negative for fusions by RNA sequencing.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, intermediate-grade. This submandibular gland tumour consisted of one cell type with monotonous dark nuclei, arranged as infiltrative solid and cribriform nests, cords, and ducts in a myxoid stroma. The tumour was negative for fusions by RNA sequencing.
Salivary gland carcinoma NOS. Adenocarcinoma NOS, high-grade. This submandibular gland tumour has irregular ducts lined by pleomorphic cells with necrosis and a high mitotic rate. There are no overtly apocrine features, and AR (not shown) was negative.

Q: A helpful microscopic finding to confirm the diagnosis of malignancy in Sclerosing Microcystic Adenocarcinoma, which otherwise features deceptively bland cytology, is the frequent presence of [...].
Sclerosing microcystic adenocarcinoma. A finding that assists in confirming a diagnosis of malignancy (i.e. adenocarcinoma) is the presence of perineural invasion, which is commonly present.
A: perineural invasion
Back Extra: Sclerosing Microcystic Adenocarcinoma
- Clinical: Sclerosing microcystic adenocarcinoma typically presents as a painless mass or swelling, affecting women more commonly than men, with a mean age of 56 years.
- Micro: The tumor is characterized by ducts/tubules, strands/cords, and nests within a densely collagenous stroma, with perineural invasion and bland cytology.
- Ancillary: Immunohistochemistry shows duct lining cells positive for pancytokeratin and CK7, while myoepithelial cells are positive for p40/p63, S100, SMA, and calponin.
Reference Gallery:
Sclerosing microcystic adenocarcinoma. A finding that assists in confirming a diagnosis of malignancy (i.e. adenocarcinoma) is the presence of perineural invasion, which is commonly present.
Sclerosing microcystic carcinoma. The neoplasm is composed of ducts and tubules, along with strands and cords within a sclerosing stroma.
Sclerosing microcystic carcinoma. The cords of neoplastic cells are usually compressed by the heavy stromal sclerosis.
Sclerosing microcystic adenocarcinoma. The myoepithelial cells are highlighted by SMA.
Sclerosing microcystic adenocarcinoma. The myoepithelial cells can also be highlighted with p40 immunohistochemistry.

Q: Microscopically, Sclerosing Microcystic Adenocarcinoma features bland epithelial ducts, tubules, and strands that are strongly compressed by a dense, heavy [...] stroma.
Sclerosing microcystic carcinoma. The neoplasm is composed of ducts and tubules, along with strands and cords within a sclerosing stroma.
Sclerosing microcystic carcinoma. The cords of neoplastic cells are usually compressed by the heavy stromal sclerosis.
A: sclerotic
Back Extra: Sclerosing Microcystic Adenocarcinoma
- Clinical: Sclerosing microcystic adenocarcinoma typically presents as a painless mass or swelling, affecting women more commonly than men, with a mean age of 56 years.
- Micro: The tumor is characterized by ducts/tubules, strands/cords, and nests within a densely collagenous stroma, with perineural invasion and bland cytology.
- Ancillary: Immunohistochemistry shows duct lining cells positive for pancytokeratin and CK7, while myoepithelial cells are positive for p40/p63, S100, SMA, and calponin.
Reference Gallery:
Sclerosing microcystic adenocarcinoma. A finding that assists in confirming a diagnosis of malignancy (i.e. adenocarcinoma) is the presence of perineural invasion, which is commonly present.
Sclerosing microcystic carcinoma. The neoplasm is composed of ducts and tubules, along with strands and cords within a sclerosing stroma.
Sclerosing microcystic carcinoma. The cords of neoplastic cells are usually compressed by the heavy stromal sclerosis.
Sclerosing microcystic adenocarcinoma. The myoepithelial cells are highlighted by SMA.
Sclerosing microcystic adenocarcinoma. The myoepithelial cells can also be highlighted with p40 immunohistochemistry.

Q: Immunohistochemistry in Sclerosing Microcystic Adenocarcinoma demonstrates an intact myoepithelial cell layer around the neoplastic ducts that can be highlighted by SMA and nuclear markers such as [...].
Sclerosing microcystic adenocarcinoma. The myoepithelial cells are highlighted by SMA.
Sclerosing microcystic adenocarcinoma. The myoepithelial cells can also be highlighted with p40 immunohistochemistry.
A: p40
Back Extra: Sclerosing Microcystic Adenocarcinoma
- Clinical: Sclerosing microcystic adenocarcinoma typically presents as a painless mass or swelling, affecting women more commonly than men, with a mean age of 56 years.
- Micro: The tumor is characterized by ducts/tubules, strands/cords, and nests within a densely collagenous stroma, with perineural invasion and bland cytology.
- Ancillary: Immunohistochemistry shows duct lining cells positive for pancytokeratin and CK7, while myoepithelial cells are positive for p40/p63, S100, SMA, and calponin.
Reference Gallery:
Sclerosing microcystic adenocarcinoma. A finding that assists in confirming a diagnosis of malignancy (i.e. adenocarcinoma) is the presence of perineural invasion, which is commonly present.
Sclerosing microcystic carcinoma. The neoplasm is composed of ducts and tubules, along with strands and cords within a sclerosing stroma.
Sclerosing microcystic carcinoma. The cords of neoplastic cells are usually compressed by the heavy stromal sclerosis.
Sclerosing microcystic adenocarcinoma. The myoepithelial cells are highlighted by SMA.
Sclerosing microcystic adenocarcinoma. The myoepithelial cells can also be highlighted with p40 immunohistochemistry.

Q: Microscopically, Sebaceous Adenocarcinoma features locally infiltrating tumor nests composed of peripheral atypical basal cells and central large, vacuolated cells that frequently demonstrate [...] secretion.
Sebaceous adenocarcinoma. Several tumour nests with prominent central sebaceous differentiation, composed of large, moderately pleomorphic, vacuolated cells with an area of holocrine secretion (centre); nuclei are pleomorphic. These cells are surrounded by atypical basal cells. A few infiltrating lymphocytes are noted.
A: holocrine
Back Extra: Sebaceous Adenocarcinoma
- Clinical: Patients with sebaceous adenocarcinoma often present with painful masses, varying degrees of facial nerve paralysis, and occasional skin fixation. Rare cases are associated with Muir–Torre syndrome.
- Micro: The tumour is composed of multiple invasive nests and sheets of cells with hyperchromatic nuclei, abundant clear vacuolated to eosinophilic cytoplasm (sebocytes), and mild to marked cellular pleomorphism. Perineural invasion is noted in about 20% of cases.
- Ancillary: Sebaceous/basal epithelial cells are positive for CK5/6, CK7, CK14, and EMA; sebocytes are positive for CD15, lactoferrin, GCDFP-2, and adipophilin. Loss of MSH2 expression is uncommon and may characterize tumours in Muir–Torre syndrome.
Reference Gallery:
Sebaceous adenocarcinoma. Locally infiltrating, closely packed tumour nests with prominent sebaceous differentiation, surrounded by peripheral basal cells with mild to moderate cytological atypia.
Sebaceous adenocarcinoma. Several tumour nests with prominent central sebaceous differentiation, composed of large, moderately pleomorphic, vacuolated cells with an area of holocrine secretion (centre); nuclei are pleomorphic. These cells are surrounded by atypical basal cells. A few infiltrating lymphocytes are noted.

Q: The pathognomonic large, vacuolated cells with clear to eosinophilic cytoplasm seen in the central tumor nests of Sebaceous Adenocarcinoma are known as [...].
Sebaceous adenocarcinoma. Locally infiltrating, closely packed tumour nests with prominent sebaceous differentiation, surrounded by peripheral basal cells with mild to moderate cytological atypia.
Sebaceous adenocarcinoma. Several tumour nests with prominent central sebaceous differentiation, composed of large, moderately pleomorphic, vacuolated cells with an area of holocrine secretion (centre); nuclei are pleomorphic. These cells are surrounded by atypical basal cells. A few infiltrating lymphocytes are noted.
A: sebocytes
Back Extra: Sebaceous Adenocarcinoma
- Clinical: Patients with sebaceous adenocarcinoma often present with painful masses, varying degrees of facial nerve paralysis, and occasional skin fixation. Rare cases are associated with Muir–Torre syndrome.
- Micro: The tumour is composed of multiple invasive nests and sheets of cells with hyperchromatic nuclei, abundant clear vacuolated to eosinophilic cytoplasm (sebocytes), and mild to marked cellular pleomorphism. Perineural invasion is noted in about 20% of cases.
- Ancillary: Sebaceous/basal epithelial cells are positive for CK5/6, CK7, CK14, and EMA; sebocytes are positive for CD15, lactoferrin, GCDFP-2, and adipophilin. Loss of MSH2 expression is uncommon and may characterize tumours in Muir–Torre syndrome.
Reference Gallery:
Sebaceous adenocarcinoma. Locally infiltrating, closely packed tumour nests with prominent sebaceous differentiation, surrounded by peripheral basal cells with mild to moderate cytological atypia.
Sebaceous adenocarcinoma. Several tumour nests with prominent central sebaceous differentiation, composed of large, moderately pleomorphic, vacuolated cells with an area of holocrine secretion (centre); nuclei are pleomorphic. These cells are surrounded by atypical basal cells. A few infiltrating lymphocytes are noted.

Q: Histologically, Secretory Carcinoma typically displays a microcystic or cribriform growth pattern filled with characteristic eosinophilic, [...] secretions.
Secretory carcinoma. Histology of a secretory carcinoma with the classic ETV6::NTRK3 fusion demonstrates a microcystic/cribriform growth pattern and homogeneous and bubbly eosinophilic secretory material.
Secretory carcinoma. Microcystic architecture, pale mucinous secretions, and typical nuclear morphology.
A: bubbly
Back Extra: Secretory Carcinoma
- Clinical: Secretory Carcinoma typically presents as a painless, slowly growing mass, and high-grade transformation is associated with aggressive clinical behavior and a poor prognosis.
- Micro: Histologically, Secretory Carcinoma shows a microcystic/cribriform growth pattern with distinctive vesicular nuclei and eosinophilic or bubbly secretions.
- Ancillary: Immunohistochemically, Secretory Carcinoma is positive for S100, SOX10, and mammaglobin, and most cases harbor the ETV6::NTRK3 fusion.
Reference Gallery:
Secretory carcinoma. Histology of a secretory carcinoma with the classic ETV6::NTRK3 fusion demonstrates a microcystic/cribriform growth pattern and homogeneous and bubbly eosinophilic secretory material.
Secretory carcinoma. Secretory carcinoma of the buccal mucosa. The tumour cells of secretory carcinoma have low-grade vesicular nuclei with finely granular chromatin and distinctive centrally located nucleoli, surrounded by pale-pink granular or vacuolated cytoplasm.
Secretory carcinoma. Secretory carcinoma of the parotid gland with ETV6::NTRK3 fusion. The papillary-cystic architectural pattern shows some degree of cyst formation with micropapillary features and hobnailing of the cells.
Secretory carcinoma with ETV6::NTRK3 fusion. Papillary-like structures and clusters of epithelial cells with rich, finely granulated cytoplasm and round to oval mildly polymorphic nuclei with discernible nucleoli in a mucinous background (FNAC, Pap).
Secretory carcinoma of the parotid gland with ETV6::RET fusion. Secretory carcinoma has a prominent fibrosclerotic stroma and a solid/microcystic structure. The tumour cells have bland, vesicular, round to oval nuclei and distinctive centrally located nucleoli.
Secretory carcinoma. Perineural invasion is seen in the upper right corner.
Secretory carcinoma. Microcystic architecture, pale mucinous secretions, and typical nuclear morphology.
Secretory carcinoma. SOX10 immunohistochemistry shows diffuse nuclear staining in the tumour cells.
Secretory carcinoma. S100 immunohistochemistry shows diffuse cytoplasmic staining in the tumour cells.
Secretory carcinoma. Mammaglobin immunohistochemistry shows diffuse cytoplasmic positivity in the tumour cells.
Secretory carcinoma of the parotid gland. Gross section of superficial parotidectomy shows a well-circumscribed haemorrhagic cystic tumour.
Secretory carcinoma of the parotid gland with high-grade transformation (ETV6::NTRK3 fusion was confirmed). Gross photograph showing an unencapsulated, haemorrhagic, infiltrative mass with a focally cystic cut surface.

Q: The defining molecular alteration in the vast majority of Secretory Carcinoma cases is the [NTRK3] gene fusion.
Secretory carcinoma. Histology of a secretory carcinoma with the classic ETV6::NTRK3 fusion demonstrates a microcystic/cribriform growth pattern and homogeneous and bubbly eosinophilic secretory material.
Secretory carcinoma. Secretory carcinoma of the parotid gland with ETV6::NTRK3 fusion. The papillary-cystic architectural pattern shows some degree of cyst formation with micropapillary features and hobnailing of the cells.
A: ETV6
Back Extra: Secretory Carcinoma
- Clinical: Secretory Carcinoma typically presents as a painless, slowly growing mass, and high-grade transformation is associated with aggressive clinical behavior and a poor prognosis.
- Micro: Histologically, Secretory Carcinoma shows a microcystic/cribriform growth pattern with distinctive vesicular nuclei and eosinophilic or bubbly secretions.
- Ancillary: Immunohistochemically, Secretory Carcinoma is positive for S100, SOX10, and mammaglobin, and most cases harbor the ETV6::NTRK3 fusion.
Reference Gallery:
Secretory carcinoma. Histology of a secretory carcinoma with the classic ETV6::NTRK3 fusion demonstrates a microcystic/cribriform growth pattern and homogeneous and bubbly eosinophilic secretory material.
Secretory carcinoma. Secretory carcinoma of the buccal mucosa. The tumour cells of secretory carcinoma have low-grade vesicular nuclei with finely granular chromatin and distinctive centrally located nucleoli, surrounded by pale-pink granular or vacuolated cytoplasm.
Secretory carcinoma. Secretory carcinoma of the parotid gland with ETV6::NTRK3 fusion. The papillary-cystic architectural pattern shows some degree of cyst formation with micropapillary features and hobnailing of the cells.
Secretory carcinoma with ETV6::NTRK3 fusion. Papillary-like structures and clusters of epithelial cells with rich, finely granulated cytoplasm and round to oval mildly polymorphic nuclei with discernible nucleoli in a mucinous background (FNAC, Pap).
Secretory carcinoma of the parotid gland with ETV6::RET fusion. Secretory carcinoma has a prominent fibrosclerotic stroma and a solid/microcystic structure. The tumour cells have bland, vesicular, round to oval nuclei and distinctive centrally located nucleoli.
Secretory carcinoma. Perineural invasion is seen in the upper right corner.
Secretory carcinoma. Microcystic architecture, pale mucinous secretions, and typical nuclear morphology.
Secretory carcinoma. SOX10 immunohistochemistry shows diffuse nuclear staining in the tumour cells.
Secretory carcinoma. S100 immunohistochemistry shows diffuse cytoplasmic staining in the tumour cells.
Secretory carcinoma. Mammaglobin immunohistochemistry shows diffuse cytoplasmic positivity in the tumour cells.
Secretory carcinoma of the parotid gland. Gross section of superficial parotidectomy shows a well-circumscribed haemorrhagic cystic tumour.
Secretory carcinoma of the parotid gland with high-grade transformation (ETV6::NTRK3 fusion was confirmed). Gross photograph showing an unencapsulated, haemorrhagic, infiltrative mass with a focally cystic cut surface.

Q: The classic immunohistochemical profile of Secretory Carcinoma consists of diffuse positivity for S100, SOX10, and [...].
Secretory carcinoma. SOX10 immunohistochemistry shows diffuse nuclear staining in the tumour cells.
Secretory carcinoma. S100 immunohistochemistry shows diffuse cytoplasmic staining in the tumour cells.
Secretory carcinoma. Mammaglobin immunohistochemistry shows diffuse cytoplasmic positivity in the tumour cells.
A: mammaglobin
Back Extra: Secretory Carcinoma
- Clinical: Secretory Carcinoma typically presents as a painless, slowly growing mass, and high-grade transformation is associated with aggressive clinical behavior and a poor prognosis.
- Micro: Histologically, Secretory Carcinoma shows a microcystic/cribriform growth pattern with distinctive vesicular nuclei and eosinophilic or bubbly secretions.
- Ancillary: Immunohistochemically, Secretory Carcinoma is positive for S100, SOX10, and mammaglobin, and most cases harbor the ETV6::NTRK3 fusion.
Reference Gallery:
Secretory carcinoma. Histology of a secretory carcinoma with the classic ETV6::NTRK3 fusion demonstrates a microcystic/cribriform growth pattern and homogeneous and bubbly eosinophilic secretory material.
Secretory carcinoma. Secretory carcinoma of the buccal mucosa. The tumour cells of secretory carcinoma have low-grade vesicular nuclei with finely granular chromatin and distinctive centrally located nucleoli, surrounded by pale-pink granular or vacuolated cytoplasm.
Secretory carcinoma. Secretory carcinoma of the parotid gland with ETV6::NTRK3 fusion. The papillary-cystic architectural pattern shows some degree of cyst formation with micropapillary features and hobnailing of the cells.
Secretory carcinoma with ETV6::NTRK3 fusion. Papillary-like structures and clusters of epithelial cells with rich, finely granulated cytoplasm and round to oval mildly polymorphic nuclei with discernible nucleoli in a mucinous background (FNAC, Pap).
Secretory carcinoma of the parotid gland with ETV6::RET fusion. Secretory carcinoma has a prominent fibrosclerotic stroma and a solid/microcystic structure. The tumour cells have bland, vesicular, round to oval nuclei and distinctive centrally located nucleoli.
Secretory carcinoma. Perineural invasion is seen in the upper right corner.
Secretory carcinoma. Microcystic architecture, pale mucinous secretions, and typical nuclear morphology.
Secretory carcinoma. SOX10 immunohistochemistry shows diffuse nuclear staining in the tumour cells.
Secretory carcinoma. S100 immunohistochemistry shows diffuse cytoplasmic staining in the tumour cells.
Secretory carcinoma. Mammaglobin immunohistochemistry shows diffuse cytoplasmic positivity in the tumour cells.
Secretory carcinoma of the parotid gland. Gross section of superficial parotidectomy shows a well-circumscribed haemorrhagic cystic tumour.
Secretory carcinoma of the parotid gland with high-grade transformation (ETV6::NTRK3 fusion was confirmed). Gross photograph showing an unencapsulated, haemorrhagic, infiltrative mass with a focally cystic cut surface.

Q: Patients with [...] typically present with a painless facial swelling in the neonatal period; histology reveals solid organoid nests of primitive basaloid epithelial cells with occasional ductal differentiation.
Sialoblastoma. Tumour cells exhibit round to oval nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Occasional differentiated ducts are noted within the tumour nests.
A: sialoblastoma
Q: Sialoblastoma
- Clinical: Patients with [...] typically present with a painless facial swelling, and the lesion is often diagnosed in the neonatal period.
- Micro: Histologically, [...] shows solid organoid nests of primitive basaloid epithelial cells with scant cytoplasm and round to oval vesicular nuclei, and occasional ductal differentiation.
- Ancillary: Immunohistochemistry for [...] is often positive in sialoblastoma, highlighting the myoepithelial differentiation.
Reference Gallery:
Sialoblastoma. CK7 shows strong immunoreactivity in the basaloid nests and ducts.
Sialoblastoma. p63 highlights the myoepithelial differentiation.
Sialoblastoma. Calponin highlights the myoepithelial differentiation.
Sialoblastoma. SMA highlights the myoepithelial differentiation.
Sialoblastoma. Tumour cells exhibit round to oval nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Occasional differentiated ducts are noted within the tumour nests.
A: sialoblastoma; sialoblastoma; CK7, p63, and calponin

Q: To confirm the dual differentiation in [...], immunohistochemistry typically shows positivity for CK7 in the ductal elements and markers such as p63 and calponin to highlight the myoepithelial differentiation.
Sialoblastoma. CK7 shows strong immunoreactivity in the basaloid nests and ducts.
Sialoblastoma. p63 highlights the myoepithelial differentiation.
Sialoblastoma. Calponin highlights the myoepithelial differentiation.
A: sialoblastoma
Q: Sialoblastoma
- Clinical: Patients with [...] typically present with a painless facial swelling, and the lesion is often diagnosed in the neonatal period.
- Micro: Histologically, [...] shows solid organoid nests of primitive basaloid epithelial cells with scant cytoplasm and round to oval vesicular nuclei, and occasional ductal differentiation.
- Ancillary: Immunohistochemistry for [...] is often positive in sialoblastoma, highlighting the myoepithelial differentiation.
Reference Gallery:
Sialoblastoma. CK7 shows strong immunoreactivity in the basaloid nests and ducts.
Sialoblastoma. p63 highlights the myoepithelial differentiation.
Sialoblastoma. Calponin highlights the myoepithelial differentiation.
Sialoblastoma. SMA highlights the myoepithelial differentiation.
Sialoblastoma. Tumour cells exhibit round to oval nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Occasional differentiated ducts are noted within the tumour nests.
A: sialoblastoma; sialoblastoma; CK7, p63, and calponin

Q: The classic microscopic features of Squamous Cell Carcinoma include infiltrating well- to moderately differentiated cells with intercellular bridges and the formation of [...].
Squamous cell carcinoma, primary in parotid gland. Invasive keratinizing squamous cell carcinoma protruding into a salivary duct. Residual intact attenuated epithelial cells line the duct superior to the carcinoma.
Squamous cell carcinoma, primary in parotid gland. Invasive squamous cell carcinoma comprising an admixture of well-, moderately, and poorly differentiated carcinoma.
A: keratin pearls
Back Extra: Squamous Cell Carcinoma
- Clinical: Primary salivary gland squamous cell carcinoma (SCC) is very rare, more common in men, and occurs mostly in the seventh to eighth decades of life.
- Micro: SCC is characterized by infiltrating well- to moderately differentiated carcinoma with desmoplasia, intracellular keratin, keratin pearl formation, and intercellular bridges.
- Ancillary: SCCs are immunoreactive for cytokeratins and p63/p40, and negative for AR, S100, mammaglobin, and DOG1.
Reference Gallery:
Squamous cell carcinoma, primary in parotid gland. Tumour showing a salivary duct lined in part by (normal) respiratory epithelial cells transitioning to squamous cell carcinoma, the latter infiltrative (centre left). Note the area of squamous metaplasia of the duct epithelium (lower right).
Squamous cell carcinoma, primary in parotid gland. Invasive keratinizing squamous cell carcinoma protruding into a salivary duct. Residual intact attenuated epithelial cells line the duct superior to the carcinoma.
Squamous cell carcinoma, primary in parotid gland. Invasive squamous cell carcinoma comprising an admixture of well-, moderately, and poorly differentiated carcinoma.

Q: Histologically, primary salivary gland Squamous Cell Carcinoma may arise from salivary ducts, occasionally demonstrating a direct transition from areas of ductal squamous [...].
Squamous cell carcinoma, primary in parotid gland. Tumour showing a salivary duct lined in part by (normal) respiratory epithelial cells transitioning to squamous cell carcinoma, the latter infiltrative (centre left). Note the area of squamous metaplasia of the duct epithelium (lower right).
A: metaplasia
Back Extra: Squamous Cell Carcinoma
- Clinical: Primary salivary gland squamous cell carcinoma (SCC) is very rare, more common in men, and occurs mostly in the seventh to eighth decades of life.
- Micro: SCC is characterized by infiltrating well- to moderately differentiated carcinoma with desmoplasia, intracellular keratin, keratin pearl formation, and intercellular bridges.
- Ancillary: SCCs are immunoreactive for cytokeratins and p63/p40, and negative for AR, S100, mammaglobin, and DOG1.
Reference Gallery:
Squamous cell carcinoma, primary in parotid gland. Tumour showing a salivary duct lined in part by (normal) respiratory epithelial cells transitioning to squamous cell carcinoma, the latter infiltrative (centre left). Note the area of squamous metaplasia of the duct epithelium (lower right).
Squamous cell carcinoma, primary in parotid gland. Invasive keratinizing squamous cell carcinoma protruding into a salivary duct. Residual intact attenuated epithelial cells line the duct superior to the carcinoma.
Squamous cell carcinoma, primary in parotid gland. Invasive squamous cell carcinoma comprising an admixture of well-, moderately, and poorly differentiated carcinoma.

Q: In Lymphoepithelial Sialadenitis, the classic histologic finding in advanced stages is a dense T cell-dominated periductal infiltrate accompanied by the presence of [...] (also known as islands).
Lymphoepithelial sialadenitis. Fully developed parotid lymphoepithelial sialadenitis with massive lymphocytic infiltration (haemalum, blue), total parenchymal atrophy, and preserved lobular architecture, with multiple lymphoepithelial lesions (CK14, brown), and reactive follicles (Ki-67, red), altogether representing an entirely reactive histological pattern (clinically Sjögren syndrome).
Lymphoepithelial sialadenitis of the parotid gland. Dense small lymphocytic infiltration accompanied by lymphoepithelial lesions (islands).
A: lymphoepithelial lesions
Back Extra: Lymphoepithelial Sialadenitis
- Clinical: Predominantly affects females in their sixth or seventh decade, presenting with sicca syndrome and bilateral parotid swelling.
- Micro: Characterized by T cell-dominated periductal lymphocytic infiltration and the presence of lymphoepithelial lesions (islands) in advanced stages.
- Ancillary: Keratin staining can help identify the frequency and distribution of lymphoepithelial lesions, and kappa/lambda light chain immunohistochemistry can demonstrate polyclonal nature.
Reference Gallery:
Lymphoepithelial sialadenitis. Minor labial gland with four foci of dense periductal lymphocytic infiltration, representing a positive focus score in a female patient with clinical Sjögren syndrome.
Lymphoepithelial sialadenitis. Fully developed parotid lymphoepithelial sialadenitis with massive lymphocytic infiltration (haemalum, blue), total parenchymal atrophy, and preserved lobular architecture, with multiple lymphoepithelial lesions (CK14, brown), and reactive follicles (Ki-67, red), altogether representing an entirely reactive histological pattern (clinically Sjögren syndrome).
Lymphoepithelial sialadenitis of the parotid gland. Dense small lymphocytic infiltration accompanied by lymphoepithelial lesions (islands).

Q: Minor salivary gland biopsies in Lymphoepithelial Sialadenitis often show dense periductal lymphocytic infiltration, which is evaluated to calculate a positive focus score in patients presenting with clinical [...].
Lymphoepithelial sialadenitis. Minor labial gland with four foci of dense periductal lymphocytic infiltration, representing a positive focus score in a female patient with clinical Sjögren syndrome.
A: Sjögren syndrome
Back Extra: Lymphoepithelial Sialadenitis
- Clinical: Predominantly affects females in their sixth or seventh decade, presenting with sicca syndrome and bilateral parotid swelling.
- Micro: Characterized by T cell-dominated periductal lymphocytic infiltration and the presence of lymphoepithelial lesions (islands) in advanced stages.
- Ancillary: Keratin staining can help identify the frequency and distribution of lymphoepithelial lesions, and kappa/lambda light chain immunohistochemistry can demonstrate polyclonal nature.
Reference Gallery:
Lymphoepithelial sialadenitis. Minor labial gland with four foci of dense periductal lymphocytic infiltration, representing a positive focus score in a female patient with clinical Sjögren syndrome.
Lymphoepithelial sialadenitis. Fully developed parotid lymphoepithelial sialadenitis with massive lymphocytic infiltration (haemalum, blue), total parenchymal atrophy, and preserved lobular architecture, with multiple lymphoepithelial lesions (CK14, brown), and reactive follicles (Ki-67, red), altogether representing an entirely reactive histological pattern (clinically Sjögren syndrome).
Lymphoepithelial sialadenitis of the parotid gland. Dense small lymphocytic infiltration accompanied by lymphoepithelial lesions (islands).

Q: To clearly highlight the characteristic epithelial islands in Lymphoepithelial Sialadenitis against the massive lymphocytic infiltrate, immunohistochemistry for [...] (such as CK14) is frequently utilized.
Lymphoepithelial sialadenitis. Fully developed parotid lymphoepithelial sialadenitis with massive lymphocytic infiltration (haemalum, blue), total parenchymal atrophy, and preserved lobular architecture, with multiple lymphoepithelial lesions (CK14, brown), and reactive follicles (Ki-67, red), altogether representing an entirely reactive histological pattern (clinically Sjögren syndrome).
A: keratin
Back Extra: Lymphoepithelial Sialadenitis
- Clinical: Predominantly affects females in their sixth or seventh decade, presenting with sicca syndrome and bilateral parotid swelling.
- Micro: Characterized by T cell-dominated periductal lymphocytic infiltration and the presence of lymphoepithelial lesions (islands) in advanced stages.
- Ancillary: Keratin staining can help identify the frequency and distribution of lymphoepithelial lesions, and kappa/lambda light chain immunohistochemistry can demonstrate polyclonal nature.
Reference Gallery:
Lymphoepithelial sialadenitis. Minor labial gland with four foci of dense periductal lymphocytic infiltration, representing a positive focus score in a female patient with clinical Sjögren syndrome.
Lymphoepithelial sialadenitis. Fully developed parotid lymphoepithelial sialadenitis with massive lymphocytic infiltration (haemalum, blue), total parenchymal atrophy, and preserved lobular architecture, with multiple lymphoepithelial lesions (CK14, brown), and reactive follicles (Ki-67, red), altogether representing an entirely reactive histological pattern (clinically Sjögren syndrome).
Lymphoepithelial sialadenitis of the parotid gland. Dense small lymphocytic infiltration accompanied by lymphoepithelial lesions (islands).

Q: Histologically, Nodular Oncocytic Hyperplasia is characterized by irregularly shaped, unencapsulated nodules composed of [...] with abundant granular cytoplasm distributed throughout the salivary parenchyma.
Nodular oncocytic hyperplasia. Nodules of oncocytes in the salivary gland parenchyma.
Nodular oncocytic hyperplasia. High-power view of nodules in the parotid gland parenchyma demonstrating oncocytic cells with granular cytoplasm.
A: oncocytes
Back Extra: Nodular Oncocytic Hyperplasia
- Clinical: Patients often present with a palpable, painless mass that has been present for years.
- Micro: Nodular oncocytic hyperplasia consists of irregularly shaped unencapsulated nodules of oncocytes with granular cytoplasm, distributed throughout the salivary parenchyma.
- Ancillary: Ancillary studies are not typically required for diagnosis.
Reference Gallery:
Nodular oncocytic hyperplasia. Nodules of oncocytes in the salivary gland parenchyma.
Nodular oncocytic hyperplasia. Extensive nodules of oncocytes in the parotid gland parenchyma.
Nodular oncocytic hyperplasia. Parotid gland showing multiple separate clear cell nodules.
Nodular oncocytic hyperplasia. High-power view of nodules in the parotid gland parenchyma demonstrating oncocytic cells with granular cytoplasm.

Q: Unlike a typical oncocytoma which forms a solitary circumscribed mass, Nodular Oncocytic Hyperplasia features multiple oncocytic nodules throughout the salivary gland that are characteristically [...].
Nodular oncocytic hyperplasia. Extensive nodules of oncocytes in the parotid gland parenchyma.
Nodular oncocytic hyperplasia. Parotid gland showing multiple separate clear cell nodules.
A: unencapsulated
Back Extra: Nodular Oncocytic Hyperplasia
- Clinical: Patients often present with a palpable, painless mass that has been present for years.
- Micro: Nodular oncocytic hyperplasia consists of irregularly shaped unencapsulated nodules of oncocytes with granular cytoplasm, distributed throughout the salivary parenchyma.
- Ancillary: Ancillary studies are not typically required for diagnosis.
Reference Gallery:
Nodular oncocytic hyperplasia. Nodules of oncocytes in the salivary gland parenchyma.
Nodular oncocytic hyperplasia. Extensive nodules of oncocytes in the parotid gland parenchyma.
Nodular oncocytic hyperplasia. Parotid gland showing multiple separate clear cell nodules.
Nodular oncocytic hyperplasia. High-power view of nodules in the parotid gland parenchyma demonstrating oncocytic cells with granular cytoplasm.

Q: Histologically, [...] exhibits a spectrum of tumor architectures, ranging from well-differentiated papillary or tubular patterns to poorly differentiated mucinous forms with signet-ring cells.
Intestinal-type sinonasal adenocarcinoma. A well-differentiated tumour showing a papillary architecture with fibrovascular cores lined by dysplastic columnar epithelium.
Intestinal-type sinonasal adenocarcinoma. A moderately differentiated tumour with a tubular arrangement of neoplastic cells.
Intestinal-type sinonasal adenocarcinoma. This mucinous tumour has a signet-ring morphology.
A: Intestinal-Type Sinonasal Adenocarcinoma
Q: Intestinal-Type Sinonasal Adenocarcinoma
- Clinical: [...] often presents with unilateral nasal obstruction, epistaxis, and rhinorrhoea. Advanced stages may present with pain, exophthalmos, and facial contour changes.
- Micro: [...] shows a spectrum of differentiation from well-differentiated papillary to poorly differentiated solid and mucinous patterns, often with goblet and Paneth cells.
- Ancillary: [...] is positive for CK20, CDX2, villin, MUC2, and SATB2. TP53 mutations are common, and high levels of EGFR expression and amplification are reported.
Reference Gallery:
Intestinal-type sinonasal adenocarcinoma. A well-differentiated tumour showing a papillary architecture with fibrovascular cores lined by dysplastic columnar epithelium.
Intestinal-type sinonasal adenocarcinoma. A moderately differentiated tumour with a tubular arrangement of neoplastic cells.
Intestinal-type sinonasal adenocarcinoma. This mucinous tumour consists of small groups of neoplastic cells dispersed within abundant mucus.
Intestinal-type sinonasal adenocarcinoma. This mucinous tumour has a signet-ring morphology.
Intestinal-type sinonasal adenocarcinoma. This tumour consists of a proliferation of dysplastic columnar cells, with interspersed goblet cells. Numerous Paneth cells with granular eosinophilic cytoplasm are also visible in this example.
A: Intestinal-Type Sinonasal Adenocarcinoma; Intestinal-Type Sinonasal Adenocarcinoma; Intestinal-Type Sinonasal Adenocarcinoma

Q: A hallmark microscopic finding of Intestinal-Type Sinonasal Adenocarcinoma is the presence of dysplastic columnar epithelium admixed with specialized gastrointestinal cell types, such as goblet cells and eosinophilic, granular [...].
Intestinal-type sinonasal adenocarcinoma. This tumour consists of a proliferation of dysplastic columnar cells, with interspersed goblet cells. Numerous Paneth cells with granular eosinophilic cytoplasm are also visible in this example.
A: Paneth cells
Q: Intestinal-Type Sinonasal Adenocarcinoma
- Clinical: [...] often presents with unilateral nasal obstruction, epistaxis, and rhinorrhoea. Advanced stages may present with pain, exophthalmos, and facial contour changes.
- Micro: [...] shows a spectrum of differentiation from well-differentiated papillary to poorly differentiated solid and mucinous patterns, often with goblet and Paneth cells.
- Ancillary: [...] is positive for CK20, CDX2, villin, MUC2, and SATB2. TP53 mutations are common, and high levels of EGFR expression and amplification are reported.
Reference Gallery:
Intestinal-type sinonasal adenocarcinoma. A well-differentiated tumour showing a papillary architecture with fibrovascular cores lined by dysplastic columnar epithelium.
Intestinal-type sinonasal adenocarcinoma. A moderately differentiated tumour with a tubular arrangement of neoplastic cells.
Intestinal-type sinonasal adenocarcinoma. This mucinous tumour consists of small groups of neoplastic cells dispersed within abundant mucus.
Intestinal-type sinonasal adenocarcinoma. This mucinous tumour has a signet-ring morphology.
Intestinal-type sinonasal adenocarcinoma. This tumour consists of a proliferation of dysplastic columnar cells, with interspersed goblet cells. Numerous Paneth cells with granular eosinophilic cytoplasm are also visible in this example.
A: Intestinal-Type Sinonasal Adenocarcinoma; Intestinal-Type Sinonasal Adenocarcinoma; Intestinal-Type Sinonasal Adenocarcinoma

Q: A sinonasal tumor composed of uniform, small glands with a papillary and tubular growth pattern that is positive for CK7 but negative for intestinal markers (e.g., CDX2) is best diagnosed as [...].
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour cells are uniform, with regular rounded nuclei with finely granular chromatin and abundant eosinophilic cytoplasm.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour consists of uniform small glands and tubular structures formed by a single row of cuboidal or columnar cells and displays a papillary growth pattern. Most papillae are simple and composed of a loose fibrovascular core and bland-looking epithelium arranged in one row or in a bilayered pattern. Some papillae are more complex, with a branching pattern.
A: Non-intestinal-type Sinonasal Adenocarcinoma
Back Extra: Non-intestinal-type Sinonasal Adenocarcinoma
- Clinical: Non-intestinal-type sinonasal adenocarcinoma (SNAC) can present with obstruction, epistaxis, and pain, with high-grade variants also showing deformity and proptosis.
- Micro: Low-grade SNACs typically show a papillary and tubular growth pattern with uniform mucinous cuboidal to columnar cells, while high-grade SNACs exhibit solid growth with mitotic figures and necrosis.
- Ancillary: Immunohistochemistry shows expression of cytokeratins (CK7) and absence of squamous antigens (p40) and intestinal markers (CDX2, SATB2, MUC2). Some cases may show β-catenin nuclear localization.
Reference Gallery:
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour cells are uniform, with regular rounded nuclei with finely granular chromatin and abundant eosinophilic cytoplasm.
Non–intestinal-type sinonasal adenocarcinoma, high-grade. This tumour was positive for high-risk HPV.
Non–intestinal-type sinonasal adenocarcinoma, high-grade. Many high-grade sinonasal adenocarcinomas have nests and ribbons of tumour cells intermixed with smaller glands or rosettes.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour consists of uniform small glands and tubular structures formed by a single row of cuboidal or columnar cells and displays a papillary growth pattern. Most papillae are simple and composed of a loose fibrovascular core and bland-looking epithelium arranged in one row or in a bilayered pattern. Some papillae are more complex, with a branching pattern.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour is composed of closely packed tubules with occasional squamous morules.
Non–intestinal-type sinonasal adenocarcinoma, high-grade. This tumour is composed of small cysts with papillae projecting into them.
Non–intestinal-type sinonasal adenocarcinoma, renal cell–like subtype. The tumour consists of a tubulopapillary proliferation of polygonal cells with optically clear cytoplasm and small, uniform, round nuclei.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. Occasional cases exhibit abnormal nuclear localization with β-catenin immunohistochemistry.

Q: In the renal cell-like subtype of Non-intestinal-type Sinonasal Adenocarcinoma, the tumor consists of a tubulopapillary proliferation of polygonal cells with optically [...] cytoplasm and small, uniform, round nuclei.
Non–intestinal-type sinonasal adenocarcinoma, renal cell–like subtype. The tumour consists of a tubulopapillary proliferation of polygonal cells with optically clear cytoplasm and small, uniform, round nuclei.
A: clear
Back Extra: Non-intestinal-type Sinonasal Adenocarcinoma
- Clinical: Non-intestinal-type sinonasal adenocarcinoma (SNAC) can present with obstruction, epistaxis, and pain, with high-grade variants also showing deformity and proptosis.
- Micro: Low-grade SNACs typically show a papillary and tubular growth pattern with uniform mucinous cuboidal to columnar cells, while high-grade SNACs exhibit solid growth with mitotic figures and necrosis.
- Ancillary: Immunohistochemistry shows expression of cytokeratins (CK7) and absence of squamous antigens (p40) and intestinal markers (CDX2, SATB2, MUC2). Some cases may show β-catenin nuclear localization.
Reference Gallery:
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour cells are uniform, with regular rounded nuclei with finely granular chromatin and abundant eosinophilic cytoplasm.
Non–intestinal-type sinonasal adenocarcinoma, high-grade. This tumour was positive for high-risk HPV.
Non–intestinal-type sinonasal adenocarcinoma, high-grade. Many high-grade sinonasal adenocarcinomas have nests and ribbons of tumour cells intermixed with smaller glands or rosettes.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour consists of uniform small glands and tubular structures formed by a single row of cuboidal or columnar cells and displays a papillary growth pattern. Most papillae are simple and composed of a loose fibrovascular core and bland-looking epithelium arranged in one row or in a bilayered pattern. Some papillae are more complex, with a branching pattern.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour is composed of closely packed tubules with occasional squamous morules.
Non–intestinal-type sinonasal adenocarcinoma, high-grade. This tumour is composed of small cysts with papillae projecting into them.
Non–intestinal-type sinonasal adenocarcinoma, renal cell–like subtype. The tumour consists of a tubulopapillary proliferation of polygonal cells with optically clear cytoplasm and small, uniform, round nuclei.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. Occasional cases exhibit abnormal nuclear localization with β-catenin immunohistochemistry.

Q: Occasional low-grade cases of Non-intestinal-type Sinonasal Adenocarcinoma can exhibit abnormal nuclear localization with [...] on immunohistochemistry.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. Occasional cases exhibit abnormal nuclear localization with β-catenin immunohistochemistry.
A: β-catenin
Back Extra: Non-intestinal-type Sinonasal Adenocarcinoma
- Clinical: Non-intestinal-type sinonasal adenocarcinoma (SNAC) can present with obstruction, epistaxis, and pain, with high-grade variants also showing deformity and proptosis.
- Micro: Low-grade SNACs typically show a papillary and tubular growth pattern with uniform mucinous cuboidal to columnar cells, while high-grade SNACs exhibit solid growth with mitotic figures and necrosis.
- Ancillary: Immunohistochemistry shows expression of cytokeratins (CK7) and absence of squamous antigens (p40) and intestinal markers (CDX2, SATB2, MUC2). Some cases may show β-catenin nuclear localization.
Reference Gallery:
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour cells are uniform, with regular rounded nuclei with finely granular chromatin and abundant eosinophilic cytoplasm.
Non–intestinal-type sinonasal adenocarcinoma, high-grade. This tumour was positive for high-risk HPV.
Non–intestinal-type sinonasal adenocarcinoma, high-grade. Many high-grade sinonasal adenocarcinomas have nests and ribbons of tumour cells intermixed with smaller glands or rosettes.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour consists of uniform small glands and tubular structures formed by a single row of cuboidal or columnar cells and displays a papillary growth pattern. Most papillae are simple and composed of a loose fibrovascular core and bland-looking epithelium arranged in one row or in a bilayered pattern. Some papillae are more complex, with a branching pattern.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. The tumour is composed of closely packed tubules with occasional squamous morules.
Non–intestinal-type sinonasal adenocarcinoma, high-grade. This tumour is composed of small cysts with papillae projecting into them.
Non–intestinal-type sinonasal adenocarcinoma, renal cell–like subtype. The tumour consists of a tubulopapillary proliferation of polygonal cells with optically clear cytoplasm and small, uniform, round nuclei.
Non–intestinal-type sinonasal adenocarcinoma, low-grade. Occasional cases exhibit abnormal nuclear localization with β-catenin immunohistochemistry.

Q: In HPV-related Multiphenotypic Sinonasal Carcinoma, the biphasic tumor contains a myoepithelial component (positive for p40 and SMA) and a ductal component characteristically highlighted by immunostaining for [...].
HPV-related multiphenotypic sinonasal carcinoma. KIT (CD117) highlights the tumour ducts, in a staining pattern that is the inverse of the myoepithelial cell marker pattern.
HPV-related multiphenotypic sinonasal carcinoma. Myoepithelial markers like p40 show an abluminal staining pattern in the myoepithelial tumour cells.
HPV-related multiphenotypic sinonasal carcinoma. Myoepithelial markers like SMA show an abluminal staining pattern in the myoepithelial tumour cells.
A: KIT (CD117)
Back Extra: HPV-related Multiphenotypic Sinonasal Carcinoma
- Clinical: Most patients with HPV-related multiphenotypic sinonasal carcinoma present with obstruction and epistaxis, and the tumour is nearly always localized to the sinonasal tract at presentation.
- Micro: The tumour grows as solid sheets, lobules, and cribriform nests of basaloid cells with myoepithelial and ductal components, often showing high-grade cellular features, a high mitotic index, and tumour necrosis.
- Ancillary: HMSC is positive for p16 and high-risk HPV by direct HPV assays. Immunostaining for p40, p63, SMA, and calponin highlights the myoepithelial component, while KIT (CD117) highlights the ductal component.
Reference Gallery:
HPV-related multiphenotypic sinonasal carcinoma. The tumour typically grows as solid and cribriform nests, with frequent myxohyaline stroma and necrosis.
HPV-related multiphenotypic sinonasal carcinoma. The predominant myoepithelial-type cells are basaloid with clear cell change, with scattered eosinophilic ducts (centre). The tumour is pleomorphic and mitotically active.
HPV-related multiphenotypic sinonasal carcinoma. KIT (CD117) highlights the tumour ducts, in a staining pattern that is the inverse of the myoepithelial cell marker pattern.
HPV-related multiphenotypic sinonasal carcinoma. The tumour, by definition, harbours high-risk HPV, here demonstrated by RNA in situ hybridization. HPV33 is the most frequently associated type.
HPV-related multiphenotypic sinonasal carcinoma. The invasive basaloid tumour (bottom) is often accompanied by high-grade squamous dysplasia of the overlying surface epithelium (top).
HPV-related multiphenotypic sinonasal carcinoma. Myoepithelial markers like p40 show an abluminal staining pattern in the myoepithelial tumour cells.
HPV-related multiphenotypic sinonasal carcinoma. Myoepithelial markers like SMA show an abluminal staining pattern in the myoepithelial tumour cells.

Q: While most HPV-driven head and neck squamous cell carcinomas are driven by HPV16, HPV-related Multiphenotypic Sinonasal Carcinoma most frequently harbors the high-risk viral subtype [...].
HPV-related multiphenotypic sinonasal carcinoma. The tumour, by definition, harbours high-risk HPV, here demonstrated by RNA in situ hybridization. HPV33 is the most frequently associated type.
A: HPV33
Back Extra: HPV-related Multiphenotypic Sinonasal Carcinoma
- Clinical: Most patients with HPV-related multiphenotypic sinonasal carcinoma present with obstruction and epistaxis, and the tumour is nearly always localized to the sinonasal tract at presentation.
- Micro: The tumour grows as solid sheets, lobules, and cribriform nests of basaloid cells with myoepithelial and ductal components, often showing high-grade cellular features, a high mitotic index, and tumour necrosis.
- Ancillary: HMSC is positive for p16 and high-risk HPV by direct HPV assays. Immunostaining for p40, p63, SMA, and calponin highlights the myoepithelial component, while KIT (CD117) highlights the ductal component.
Reference Gallery:
HPV-related multiphenotypic sinonasal carcinoma. The tumour typically grows as solid and cribriform nests, with frequent myxohyaline stroma and necrosis.
HPV-related multiphenotypic sinonasal carcinoma. The predominant myoepithelial-type cells are basaloid with clear cell change, with scattered eosinophilic ducts (centre). The tumour is pleomorphic and mitotically active.
HPV-related multiphenotypic sinonasal carcinoma. KIT (CD117) highlights the tumour ducts, in a staining pattern that is the inverse of the myoepithelial cell marker pattern.
HPV-related multiphenotypic sinonasal carcinoma. The tumour, by definition, harbours high-risk HPV, here demonstrated by RNA in situ hybridization. HPV33 is the most frequently associated type.
HPV-related multiphenotypic sinonasal carcinoma. The invasive basaloid tumour (bottom) is often accompanied by high-grade squamous dysplasia of the overlying surface epithelium (top).
HPV-related multiphenotypic sinonasal carcinoma. Myoepithelial markers like p40 show an abluminal staining pattern in the myoepithelial tumour cells.
HPV-related multiphenotypic sinonasal carcinoma. Myoepithelial markers like SMA show an abluminal staining pattern in the myoepithelial tumour cells.

Q: A mitotically active, biphasic sinonasal tumor composed of basaloid myoepithelial cells and eosinophilic ducts, which is frequently accompanied by high-grade squamous dysplasia of the overlying surface epithelium, is characteristic of [...].
HPV-related multiphenotypic sinonasal carcinoma. The predominant myoepithelial-type cells are basaloid with clear cell change, with scattered eosinophilic ducts (centre). The tumour is pleomorphic and mitotically active.
HPV-related multiphenotypic sinonasal carcinoma. The invasive basaloid tumour (bottom) is often accompanied by high-grade squamous dysplasia of the overlying surface epithelium (top).
A: HPV-related Multiphenotypic Sinonasal Carcinoma
Back Extra: HPV-related Multiphenotypic Sinonasal Carcinoma
- Clinical: Most patients with HPV-related multiphenotypic sinonasal carcinoma present with obstruction and epistaxis, and the tumour is nearly always localized to the sinonasal tract at presentation.
- Micro: The tumour grows as solid sheets, lobules, and cribriform nests of basaloid cells with myoepithelial and ductal components, often showing high-grade cellular features, a high mitotic index, and tumour necrosis.
- Ancillary: HMSC is positive for p16 and high-risk HPV by direct HPV assays. Immunostaining for p40, p63, SMA, and calponin highlights the myoepithelial component, while KIT (CD117) highlights the ductal component.
Reference Gallery:
HPV-related multiphenotypic sinonasal carcinoma. The tumour typically grows as solid and cribriform nests, with frequent myxohyaline stroma and necrosis.
HPV-related multiphenotypic sinonasal carcinoma. The predominant myoepithelial-type cells are basaloid with clear cell change, with scattered eosinophilic ducts (centre). The tumour is pleomorphic and mitotically active.
HPV-related multiphenotypic sinonasal carcinoma. KIT (CD117) highlights the tumour ducts, in a staining pattern that is the inverse of the myoepithelial cell marker pattern.
HPV-related multiphenotypic sinonasal carcinoma. The tumour, by definition, harbours high-risk HPV, here demonstrated by RNA in situ hybridization. HPV33 is the most frequently associated type.
HPV-related multiphenotypic sinonasal carcinoma. The invasive basaloid tumour (bottom) is often accompanied by high-grade squamous dysplasia of the overlying surface epithelium (top).
HPV-related multiphenotypic sinonasal carcinoma. Myoepithelial markers like p40 show an abluminal staining pattern in the myoepithelial tumour cells.
HPV-related multiphenotypic sinonasal carcinoma. Myoepithelial markers like SMA show an abluminal staining pattern in the myoepithelial tumour cells.

Q: Histologically, Keratinizing Squamous Cell Carcinoma features infiltrative proliferations of malignant epithelial cells with squamous differentiation, primarily identified by the presence of intercellular bridges and [...] production.
Keratinizing squamous cell carcinoma. Proliferation of malignant epithelial cells with squamous differentiation and intercellular bridges.
Keratinizing squamous cell carcinoma. Keratin production is frequent.
A: keratin
Q: Keratinizing Squamous Cell Carcinoma
- Clinical: Patients with [...] often present with nasal obstruction, facial pain, rhinorrhoea, and epistaxis.
- Micro: Histologically, [...] shows infiltrative proliferations of malignant epithelial cells with squamous differentiation, intercellular bridges, and keratin production.
- Ancillary: Immunohistochemistry in [...] typically shows positivity for pancytokeratin, p40, p63, and CK5/6.
Reference Gallery:
Keratinizing squamous cell carcinoma. Proliferation of malignant epithelial cells with squamous differentiation and intercellular bridges.
Keratinizing squamous cell carcinoma. Keratin production is frequent.
Keratinizing squamous cell carcinoma. T1-weighted axial MRI demonstrates a large tumour centred on the left maxillary sinus, extending into the soft tissues of the cheek, masticator space, and retromaxillary fat, involving the pterygoid process and pterygomaxillary region.
Keratinizing squamous cell carcinoma. Fat-suppressed T1-weighted axial MRI demonstrates a large tumour centred on the left maxillary sinus, extending into the soft tissues of the cheek, masticator space, and retromaxillary fat, involving the pterygoid process and pterygomaxillary region.
Keratinizing squamous cell carcinoma. Axial apparent diffusion coefficient map demonstrates a large tumour centred on the left maxillary sinus, extending into the soft tissues of the cheek, masticator space, and retromaxillary fat, involving the pterygoid process and pterygomaxillary region. Note its low apparent diffusion coefficient value, consistent with a highly cellular mass.
A: keratinizing squamous cell carcinoma; keratinizing squamous cell carcinoma; keratinizing squamous cell carcinoma

Q: Patients with sinonasal [...] often present with nasal obstruction, rhinorrhea, and epistaxis; MRI frequently reveals a large, infiltrative tumor (e.g., centered on the maxillary sinus) with high cellularity on ADC maps.
Keratinizing squamous cell carcinoma. T1-weighted axial MRI demonstrates a large tumour centred on the left maxillary sinus, extending into the soft tissues of the cheek, masticator space, and retromaxillary fat, involving the pterygoid process and pterygomaxillary region.
Keratinizing squamous cell carcinoma. Fat-suppressed T1-weighted axial MRI demonstrates a large tumour centred on the left maxillary sinus, extending into the soft tissues of the cheek, masticator space, and retromaxillary fat, involving the pterygoid process and pterygomaxillary region.
Keratinizing squamous cell carcinoma. Axial apparent diffusion coefficient map demonstrates a large tumour centred on the left maxillary sinus, extending into the soft tissues of the cheek, masticator space, and retromaxillary fat, involving the pterygoid process and pterygomaxillary region. Note its low apparent diffusion coefficient value, consistent with a highly cellular mass.
A: Keratinizing Squamous Cell Carcinoma
Q: Keratinizing Squamous Cell Carcinoma
- Clinical: Patients with [...] often present with nasal obstruction, facial pain, rhinorrhoea, and epistaxis.
- Micro: Histologically, [...] shows infiltrative proliferations of malignant epithelial cells with squamous differentiation, intercellular bridges, and keratin production.
- Ancillary: Immunohistochemistry in [...] typically shows positivity for pancytokeratin, p40, p63, and CK5/6.
Reference Gallery:
Keratinizing squamous cell carcinoma. Proliferation of malignant epithelial cells with squamous differentiation and intercellular bridges.
Keratinizing squamous cell carcinoma. Keratin production is frequent.
Keratinizing squamous cell carcinoma. T1-weighted axial MRI demonstrates a large tumour centred on the left maxillary sinus, extending into the soft tissues of the cheek, masticator space, and retromaxillary fat, involving the pterygoid process and pterygomaxillary region.
Keratinizing squamous cell carcinoma. Fat-suppressed T1-weighted axial MRI demonstrates a large tumour centred on the left maxillary sinus, extending into the soft tissues of the cheek, masticator space, and retromaxillary fat, involving the pterygoid process and pterygomaxillary region.
Keratinizing squamous cell carcinoma. Axial apparent diffusion coefficient map demonstrates a large tumour centred on the left maxillary sinus, extending into the soft tissues of the cheek, masticator space, and retromaxillary fat, involving the pterygoid process and pterygomaxillary region. Note its low apparent diffusion coefficient value, consistent with a highly cellular mass.
A: keratinizing squamous cell carcinoma; keratinizing squamous cell carcinoma; keratinizing squamous cell carcinoma

Q: Histologically, Non-Keratinizing Squamous Cell Carcinoma is characterized by expansile nests, lobules, or broad ribbons with pushing borders, high N:C ratios (appearing basophilic), and [...].
Non-keratinizing squamous cell carcinoma. Nested and lobulated growth of cells with high N:C ratios and no keratinization, with peripheral palisading and minimal stromal desmoplasia.
Non-keratinizing squamous cell carcinoma. The classic growth pattern of non-keratinizing squamous cell carcinoma is partially papillary and exophytic, with invasion as broad, pushing, smooth-edged ribbons. This pattern is reminiscent of inverted papilloma, but non-keratinizing squamous cell carcinoma is much more basophilic, owing to the high N:C ratios of the neoplastic cells.
A: minimal or no keratinization
Back Extra: Non-Keratinizing Squamous Cell Carcinoma
- Clinical: Patients with Non-Keratinizing Squamous Cell Carcinoma (NKSCC) often present with nasal obstruction, epistaxis, and pain, with imaging showing an aggressive soft tissue lesion and bony destruction.
- Micro: NKSCC is characterized by expansile nests, lobules, or ribbons with a pushing pattern of invasion, high N:C ratios, and minimal keratinization.
- Ancillary: HPV-associated NKSCC can be identified by p16 overexpression and PCR positivity for high-risk HPV.
Reference Gallery:
Non-keratinizing squamous cell carcinoma. Nested and lobulated growth of cells with high N:C ratios and no keratinization, with peripheral palisading and minimal stromal desmoplasia.
Non-keratinizing squamous cell carcinoma. Predominantly papillary growth can be seen in a subset of tumours, and cytological atypia can vary widely.
Non-keratinizing squamous cell carcinoma. HPV-associated squamous cell carcinoma is a subtype of non-keratinizing squamous cell carcinoma defined by the presence of transcriptionally active high-risk HPV, highlighted here by RNA in situ hybridization.
Non-keratinizing squamous cell carcinoma, DEK::AFF2 subtype. Confluent exophytic and endophytic growth with surface epithelial discohesion and strikingly monotonous oval nuclei.
Non-keratinizing squamous cell carcinoma, DEK::AFF2 subtype. Dense tumour-infiltrating neutrophils are frequently seen.
Non-keratinizing squamous cell carcinoma. The classic growth pattern of non-keratinizing squamous cell carcinoma is partially papillary and exophytic, with invasion as broad, pushing, smooth-edged ribbons. This pattern is reminiscent of inverted papilloma, but non-keratinizing squamous cell carcinoma is much more basophilic, owing to the high N:C ratios of the neoplastic cells.
Non-keratinizing squamous cell carcinoma. Coronal CT (bone window) shows a large soft-tissue lesion filling the left nasal cavity, with attenuation of the left lamina papyracea.
Non-keratinizing squamous cell carcinoma. Coronal short-tau inversion recovery (STIR) MRI shows clear differentiation between the soft tissue tumour (intermediate signal) extending into the left maxillary sinus and the retained sinus secretions (high signal).
Non-keratinizing squamous cell carcinoma. Postcontrast fat-suppressed T1-weighted axial MRI shows linear cerebriform enhancement, suggesting that this non-keratinizing squamous cell carcinoma may have arisen from inverted papilloma.

Q: A specific subtype of Non-Keratinizing Squamous Cell Carcinoma is driven by transcriptionally active high-risk HPV, which can be directly highlighted microscopically using [...].
Non-keratinizing squamous cell carcinoma. HPV-associated squamous cell carcinoma is a subtype of non-keratinizing squamous cell carcinoma defined by the presence of transcriptionally active high-risk HPV, highlighted here by RNA in situ hybridization.
A: RNA in situ hybridization
Back Extra: Non-Keratinizing Squamous Cell Carcinoma
- Clinical: Patients with Non-Keratinizing Squamous Cell Carcinoma (NKSCC) often present with nasal obstruction, epistaxis, and pain, with imaging showing an aggressive soft tissue lesion and bony destruction.
- Micro: NKSCC is characterized by expansile nests, lobules, or ribbons with a pushing pattern of invasion, high N:C ratios, and minimal keratinization.
- Ancillary: HPV-associated NKSCC can be identified by p16 overexpression and PCR positivity for high-risk HPV.
Reference Gallery:
Non-keratinizing squamous cell carcinoma. Nested and lobulated growth of cells with high N:C ratios and no keratinization, with peripheral palisading and minimal stromal desmoplasia.
Non-keratinizing squamous cell carcinoma. Predominantly papillary growth can be seen in a subset of tumours, and cytological atypia can vary widely.
Non-keratinizing squamous cell carcinoma. HPV-associated squamous cell carcinoma is a subtype of non-keratinizing squamous cell carcinoma defined by the presence of transcriptionally active high-risk HPV, highlighted here by RNA in situ hybridization.
Non-keratinizing squamous cell carcinoma, DEK::AFF2 subtype. Confluent exophytic and endophytic growth with surface epithelial discohesion and strikingly monotonous oval nuclei.
Non-keratinizing squamous cell carcinoma, DEK::AFF2 subtype. Dense tumour-infiltrating neutrophils are frequently seen.
Non-keratinizing squamous cell carcinoma. The classic growth pattern of non-keratinizing squamous cell carcinoma is partially papillary and exophytic, with invasion as broad, pushing, smooth-edged ribbons. This pattern is reminiscent of inverted papilloma, but non-keratinizing squamous cell carcinoma is much more basophilic, owing to the high N:C ratios of the neoplastic cells.
Non-keratinizing squamous cell carcinoma. Coronal CT (bone window) shows a large soft-tissue lesion filling the left nasal cavity, with attenuation of the left lamina papyracea.
Non-keratinizing squamous cell carcinoma. Coronal short-tau inversion recovery (STIR) MRI shows clear differentiation between the soft tissue tumour (intermediate signal) extending into the left maxillary sinus and the retained sinus secretions (high signal).
Non-keratinizing squamous cell carcinoma. Postcontrast fat-suppressed T1-weighted axial MRI shows linear cerebriform enhancement, suggesting that this non-keratinizing squamous cell carcinoma may have arisen from inverted papilloma.

Q: On postcontrast MRI, a Non-Keratinizing Squamous Cell Carcinoma that arises from an underlying inverted papilloma may demonstrate a characteristic linear [...] enhancement pattern.
Non-keratinizing squamous cell carcinoma. Postcontrast fat-suppressed T1-weighted axial MRI shows linear cerebriform enhancement, suggesting that this non-keratinizing squamous cell carcinoma may have arisen from inverted papilloma.
A: cerebriform
Back Extra: Non-Keratinizing Squamous Cell Carcinoma
- Clinical: Patients with Non-Keratinizing Squamous Cell Carcinoma (NKSCC) often present with nasal obstruction, epistaxis, and pain, with imaging showing an aggressive soft tissue lesion and bony destruction.
- Micro: NKSCC is characterized by expansile nests, lobules, or ribbons with a pushing pattern of invasion, high N:C ratios, and minimal keratinization.
- Ancillary: HPV-associated NKSCC can be identified by p16 overexpression and PCR positivity for high-risk HPV.
Reference Gallery:
Non-keratinizing squamous cell carcinoma. Nested and lobulated growth of cells with high N:C ratios and no keratinization, with peripheral palisading and minimal stromal desmoplasia.
Non-keratinizing squamous cell carcinoma. Predominantly papillary growth can be seen in a subset of tumours, and cytological atypia can vary widely.
Non-keratinizing squamous cell carcinoma. HPV-associated squamous cell carcinoma is a subtype of non-keratinizing squamous cell carcinoma defined by the presence of transcriptionally active high-risk HPV, highlighted here by RNA in situ hybridization.
Non-keratinizing squamous cell carcinoma, DEK::AFF2 subtype. Confluent exophytic and endophytic growth with surface epithelial discohesion and strikingly monotonous oval nuclei.
Non-keratinizing squamous cell carcinoma, DEK::AFF2 subtype. Dense tumour-infiltrating neutrophils are frequently seen.
Non-keratinizing squamous cell carcinoma. The classic growth pattern of non-keratinizing squamous cell carcinoma is partially papillary and exophytic, with invasion as broad, pushing, smooth-edged ribbons. This pattern is reminiscent of inverted papilloma, but non-keratinizing squamous cell carcinoma is much more basophilic, owing to the high N:C ratios of the neoplastic cells.
Non-keratinizing squamous cell carcinoma. Coronal CT (bone window) shows a large soft-tissue lesion filling the left nasal cavity, with attenuation of the left lamina papyracea.
Non-keratinizing squamous cell carcinoma. Coronal short-tau inversion recovery (STIR) MRI shows clear differentiation between the soft tissue tumour (intermediate signal) extending into the left maxillary sinus and the retained sinus secretions (high signal).
Non-keratinizing squamous cell carcinoma. Postcontrast fat-suppressed T1-weighted axial MRI shows linear cerebriform enhancement, suggesting that this non-keratinizing squamous cell carcinoma may have arisen from inverted papilloma.

Q: Microscopically, NUT carcinoma typically features sheets of monomorphic, undifferentiated cells often accompanied by characteristic [...].
NUT carcinoma. Sheet-like growth pattern of round, medium-sized, monomorphic cells with distinct nucleoli and vesicular open chromatin. The glycogenated, clear cytoplasm gives the cells a fried egg–like appearance. Single cell necrosis and frequent mitoses are seen.
NUT carcinoma. Abrupt, keratinized squamous differentiation is a characteristic feature, seen in 33% of cases.
A: abrupt keratinization
Q: NUT Carcinoma
- Clinical: Patients with [...] present with symptoms caused by a rapidly growing mass, including nasal obstruction, pain, and epistaxis.
- Micro: [...] shows sheets and nests of small to intermediate-sized undifferentiated cells with a monomorphic appearance and prominent nucleoli.
- Ancillary: [...] is diagnosed by demonstrating NUTM1 rearrangement, often using FISH or immunohistochemistry for nuclear NUT staining.
Reference Gallery:
NUT carcinoma. Axial non-contrast CT shows a destructive soft tissue mass containing coarse foci of calcification centred on the right nasal cavity / ethmoid air cells.
NUT carcinoma. Pap of an FNA of a head and neck primary NUT carcinoma reveals some spindling of medium-sized monomorphic cells with delicate cytoplasm and distinct nucleoli.
NUT carcinoma. Sheet-like growth pattern of round, medium-sized, monomorphic cells with distinct nucleoli and vesicular open chromatin. The glycogenated, clear cytoplasm gives the cells a fried egg–like appearance. Single cell necrosis and frequent mitoses are seen.
NUT carcinoma. Abrupt, keratinized squamous differentiation is a characteristic feature, seen in 33% of cases.
NUT carcinoma. Schematic of predicted NUT fusions and respective wildtype proteins. Arrows indicate breakpoints. PWWP, proline-tryptophan-tryptophan-proline domain; PHD, plant homeodomain; SET, Su(var)3–9, enhancer of zeste, and trithorax domain; C/H rich, cysteine/histidine–rich domain; NLS, nuclear localization signal; NES, nuclear export signal; Bromo, bromodomain; ET, extraterminal domain.
NUT carcinoma. FISH demonstrates BRD4 rearrangement by the splitting apart of red and green DNA probes flanking the BRD4 genomic locus. Demonstration by FISH of BRD4 and NUTM1 break-apart indicates a BRD4::NUT fusion.
NUT carcinoma. Diffuse nuclear staining with the NUT monoclonal antibody (clone C52B1). The speckled pattern of staining is characteristic.
NUT carcinoma. Kaplan–Meier overall survival curves of NUT carcinoma patient risk groups defined on the basis of anatomical location and NUTM1 fusion partner.
A: NUT carcinoma; NUT carcinoma; NUT carcinoma

Q: Immunohistochemistry for NUT carcinoma is highly specific, demonstrating a characteristic speckled nuclear staining pattern for the [...] protein.
NUT carcinoma. Diffuse nuclear staining with the NUT monoclonal antibody (clone C52B1). The speckled pattern of staining is characteristic.
A: NUT
Q: NUT Carcinoma
- Clinical: Patients with [...] present with symptoms caused by a rapidly growing mass, including nasal obstruction, pain, and epistaxis.
- Micro: [...] shows sheets and nests of small to intermediate-sized undifferentiated cells with a monomorphic appearance and prominent nucleoli.
- Ancillary: [...] is diagnosed by demonstrating NUTM1 rearrangement, often using FISH or immunohistochemistry for nuclear NUT staining.
Reference Gallery:
NUT carcinoma. Axial non-contrast CT shows a destructive soft tissue mass containing coarse foci of calcification centred on the right nasal cavity / ethmoid air cells.
NUT carcinoma. Pap of an FNA of a head and neck primary NUT carcinoma reveals some spindling of medium-sized monomorphic cells with delicate cytoplasm and distinct nucleoli.
NUT carcinoma. Sheet-like growth pattern of round, medium-sized, monomorphic cells with distinct nucleoli and vesicular open chromatin. The glycogenated, clear cytoplasm gives the cells a fried egg–like appearance. Single cell necrosis and frequent mitoses are seen.
NUT carcinoma. Abrupt, keratinized squamous differentiation is a characteristic feature, seen in 33% of cases.
NUT carcinoma. Schematic of predicted NUT fusions and respective wildtype proteins. Arrows indicate breakpoints. PWWP, proline-tryptophan-tryptophan-proline domain; PHD, plant homeodomain; SET, Su(var)3–9, enhancer of zeste, and trithorax domain; C/H rich, cysteine/histidine–rich domain; NLS, nuclear localization signal; NES, nuclear export signal; Bromo, bromodomain; ET, extraterminal domain.
NUT carcinoma. FISH demonstrates BRD4 rearrangement by the splitting apart of red and green DNA probes flanking the BRD4 genomic locus. Demonstration by FISH of BRD4 and NUTM1 break-apart indicates a BRD4::NUT fusion.
NUT carcinoma. Diffuse nuclear staining with the NUT monoclonal antibody (clone C52B1). The speckled pattern of staining is characteristic.
NUT carcinoma. Kaplan–Meier overall survival curves of NUT carcinoma patient risk groups defined on the basis of anatomical location and NUTM1 fusion partner.
A: NUT carcinoma; NUT carcinoma; NUT carcinoma

Q: The defining molecular driver of NUT carcinoma is the chromosomal rearrangement of the [...] gene, most commonly fusing with BRD4 (which can be detected via FISH).
NUT carcinoma. Schematic of predicted NUT fusions and respective wildtype proteins. Arrows indicate breakpoints. PWWP, proline-tryptophan-tryptophan-proline domain; PHD, plant homeodomain; SET, Su(var)3–9, enhancer of zeste, and trithorax domain; C/H rich, cysteine/histidine–rich domain; NLS, nuclear localization signal; NES, nuclear export signal; Bromo, bromodomain; ET, extraterminal domain.
NUT carcinoma. FISH demonstrates BRD4 rearrangement by the splitting apart of red and green DNA probes flanking the BRD4 genomic locus. Demonstration by FISH of BRD4 and NUTM1 break-apart indicates a BRD4::NUT fusion.
A: NUTM1
Q: NUT Carcinoma
- Clinical: Patients with [...] present with symptoms caused by a rapidly growing mass, including nasal obstruction, pain, and epistaxis.
- Micro: [...] shows sheets and nests of small to intermediate-sized undifferentiated cells with a monomorphic appearance and prominent nucleoli.
- Ancillary: [...] is diagnosed by demonstrating NUTM1 rearrangement, often using FISH or immunohistochemistry for nuclear NUT staining.
Reference Gallery:
NUT carcinoma. Axial non-contrast CT shows a destructive soft tissue mass containing coarse foci of calcification centred on the right nasal cavity / ethmoid air cells.
NUT carcinoma. Pap of an FNA of a head and neck primary NUT carcinoma reveals some spindling of medium-sized monomorphic cells with delicate cytoplasm and distinct nucleoli.
NUT carcinoma. Sheet-like growth pattern of round, medium-sized, monomorphic cells with distinct nucleoli and vesicular open chromatin. The glycogenated, clear cytoplasm gives the cells a fried egg–like appearance. Single cell necrosis and frequent mitoses are seen.
NUT carcinoma. Abrupt, keratinized squamous differentiation is a characteristic feature, seen in 33% of cases.
NUT carcinoma. Schematic of predicted NUT fusions and respective wildtype proteins. Arrows indicate breakpoints. PWWP, proline-tryptophan-tryptophan-proline domain; PHD, plant homeodomain; SET, Su(var)3–9, enhancer of zeste, and trithorax domain; C/H rich, cysteine/histidine–rich domain; NLS, nuclear localization signal; NES, nuclear export signal; Bromo, bromodomain; ET, extraterminal domain.
NUT carcinoma. FISH demonstrates BRD4 rearrangement by the splitting apart of red and green DNA probes flanking the BRD4 genomic locus. Demonstration by FISH of BRD4 and NUTM1 break-apart indicates a BRD4::NUT fusion.
NUT carcinoma. Diffuse nuclear staining with the NUT monoclonal antibody (clone C52B1). The speckled pattern of staining is characteristic.
NUT carcinoma. Kaplan–Meier overall survival curves of NUT carcinoma patient risk groups defined on the basis of anatomical location and NUTM1 fusion partner.
A: NUT carcinoma; NUT carcinoma; NUT carcinoma

Q: A defining histologic feature of Sinonasal Lymphoepithelial Carcinoma is the presence of solid nests and trabeculae of tumor cells admixed with a marked [...] inflammatory infiltrate.
Sinonasal lymphoepithelial carcinoma. A mass composed of solid nests and trabeculae of tumour cells accompanied by a marked inflammatory infiltrate of lymphocytes and plasma cells.
Sinonasal lymphoepithelial carcinoma. Tumour cells show large nuclei, vesicular chromatin, prominent nucleoli, indistinct cell borders, and an associated inflammatory infiltrate of lymphocytes and plasma cells.
A: lymphoplasmacytic
Back Extra: Sinonasal Lymphoepithelial Carcinoma
- Clinical: Patients typically present with nasal obstruction, bloody nasal discharge, facial swelling, and pain, and the tumour is more common in men in their fifth to seventh decade of life.
- Micro: Tumour cells are arranged in nests, trabeculae, or cords with a rich lymphoplasmacytic infiltrate and large, vesicular nuclei with prominent nucleoli.
- Ancillary: Tumour cells are positive for cytokeratins and EBV-encoded small RNA (EBER) by in situ hybridization.
Reference Gallery:
Sinonasal lymphoepithelial carcinoma. A mass composed of solid nests and trabeculae of tumour cells accompanied by a marked inflammatory infiltrate of lymphocytes and plasma cells.
Sinonasal lymphoepithelial carcinoma. Thick, fibrous bands separating tumour islands can be observed.
Sinonasal lymphoepithelial carcinoma. Tumour cells show large nuclei, vesicular chromatin, prominent nucleoli, indistinct cell borders, and an associated inflammatory infiltrate of lymphocytes and plasma cells.
Sinonasal lymphoepithelial carcinoma. Most cases are positive for EBV-encoded small RNA (EBER) by in situ hybridization.

Q: The vast majority of Sinonasal Lymphoepithelial Carcinoma cases are driven by Epstein-Barr virus (EBV), which is classically confirmed by ancillary testing showing positivity for [...] via in situ hybridization.
Sinonasal lymphoepithelial carcinoma. Most cases are positive for EBV-encoded small RNA (EBER) by in situ hybridization.
A: EBER
Back Extra: Sinonasal Lymphoepithelial Carcinoma
- Clinical: Patients typically present with nasal obstruction, bloody nasal discharge, facial swelling, and pain, and the tumour is more common in men in their fifth to seventh decade of life.
- Micro: Tumour cells are arranged in nests, trabeculae, or cords with a rich lymphoplasmacytic infiltrate and large, vesicular nuclei with prominent nucleoli.
- Ancillary: Tumour cells are positive for cytokeratins and EBV-encoded small RNA (EBER) by in situ hybridization.
Reference Gallery:
Sinonasal lymphoepithelial carcinoma. A mass composed of solid nests and trabeculae of tumour cells accompanied by a marked inflammatory infiltrate of lymphocytes and plasma cells.
Sinonasal lymphoepithelial carcinoma. Thick, fibrous bands separating tumour islands can be observed.
Sinonasal lymphoepithelial carcinoma. Tumour cells show large nuclei, vesicular chromatin, prominent nucleoli, indistinct cell borders, and an associated inflammatory infiltrate of lymphocytes and plasma cells.
Sinonasal lymphoepithelial carcinoma. Most cases are positive for EBV-encoded small RNA (EBER) by in situ hybridization.

Q: Microscopically, [...] is an aggressive neoplasm characterized by sheets, lobules, and trabeculae of malignant cells with enlarged vesicular nuclei, high N:C ratios, prominent nucleoli, and abundant necrosis.
Sinonasal undifferentiated carcinoma. Lobules, trabeculae, and nests of malignant epithelial cells.
Sinonasal undifferentiated carcinoma. Invasion into bone by tumour cells and abundant necrosis.
Sinonasal undifferentiated carcinoma. Undifferentiated tumour cell population showing a high N:C ratio, an open or vesicular chromatin pattern, and prominent nucleoli.
A: sinonasal undifferentiated carcinoma
Q: Sinonasal Undifferentiated Carcinoma
- Clinical: Common presenting symptoms of [...] include nasal obstruction, sinusitis, epistaxis, and/or headache.
- Micro: [...] is characterized by sheets, lobules, nests, and trabeculae of malignant cells with enlarged round nuclei and prominent nucleoli.
- Ancillary: [...] is positive for cytokeratins and may show IDH2 hotspot mutations, particularly p.R172S.
Reference Gallery:
Sinonasal undifferentiated carcinoma. Lobules, trabeculae, and nests of malignant epithelial cells.
Sinonasal undifferentiated carcinoma. Invasion into bone by tumour cells and abundant necrosis.
Sinonasal undifferentiated carcinoma. Undifferentiated tumour cell population showing a high N:C ratio, an open or vesicular chromatin pattern, and prominent nucleoli.
Sinonasal undifferentiated carcinoma. Tumour showing more basaloid morphology.
Sinonasal undifferentiated carcinoma. IDH2 p.R172S showing granular cytoplasmic staining for a multispecific antibody for mutant IDH1/2 p.R132/172 (clone MsMab-1).
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This coronal short-tau inversion recovery (STIR) image demonstrates an intermediate-signal tumour, high-signal secretions in the obstructed left maxillary sinus, and vasogenic oedema in the left frontal lobe.
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This coronal postcontrast fat-suppressed T1-weighted image shows the extent of the tumour and its proximity to the left optic nerve.
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This sagittal postcontrast T1-weighted image shows extension across the cribriform plate into the anterior cranial fossa and involvement of the sphenoid sinus.
A: Sinonasal Undifferentiated Carcinoma; Sinonasal Undifferentiated Carcinoma; Sinonasal Undifferentiated Carcinoma

Q: A distinct subset of sinonasal undifferentiated carcinoma is driven by specific hotspot mutations in the [...] gene, which can be detected using immunohistochemistry targeting the mutant p.R172S protein.
Sinonasal undifferentiated carcinoma. IDH2 p.R172S showing granular cytoplasmic staining for a multispecific antibody for mutant IDH1/2 p.R132/172 (clone MsMab-1).
A: IDH2
Q: Sinonasal Undifferentiated Carcinoma
- Clinical: Common presenting symptoms of [...] include nasal obstruction, sinusitis, epistaxis, and/or headache.
- Micro: [...] is characterized by sheets, lobules, nests, and trabeculae of malignant cells with enlarged round nuclei and prominent nucleoli.
- Ancillary: [...] is positive for cytokeratins and may show IDH2 hotspot mutations, particularly p.R172S.
Reference Gallery:
Sinonasal undifferentiated carcinoma. Lobules, trabeculae, and nests of malignant epithelial cells.
Sinonasal undifferentiated carcinoma. Invasion into bone by tumour cells and abundant necrosis.
Sinonasal undifferentiated carcinoma. Undifferentiated tumour cell population showing a high N:C ratio, an open or vesicular chromatin pattern, and prominent nucleoli.
Sinonasal undifferentiated carcinoma. Tumour showing more basaloid morphology.
Sinonasal undifferentiated carcinoma. IDH2 p.R172S showing granular cytoplasmic staining for a multispecific antibody for mutant IDH1/2 p.R132/172 (clone MsMab-1).
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This coronal short-tau inversion recovery (STIR) image demonstrates an intermediate-signal tumour, high-signal secretions in the obstructed left maxillary sinus, and vasogenic oedema in the left frontal lobe.
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This coronal postcontrast fat-suppressed T1-weighted image shows the extent of the tumour and its proximity to the left optic nerve.
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This sagittal postcontrast T1-weighted image shows extension across the cribriform plate into the anterior cranial fossa and involvement of the sphenoid sinus.
A: Sinonasal Undifferentiated Carcinoma; Sinonasal Undifferentiated Carcinoma; Sinonasal Undifferentiated Carcinoma

Q: Radiologically, [...] frequently presents as a large, destructive mass characteristically centered in the ethmoid air cells with extensive orbital and intracranial extension.
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This coronal short-tau inversion recovery (STIR) image demonstrates an intermediate-signal tumour, high-signal secretions in the obstructed left maxillary sinus, and vasogenic oedema in the left frontal lobe.
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This coronal postcontrast fat-suppressed T1-weighted image shows the extent of the tumour and its proximity to the left optic nerve.
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This sagittal postcontrast T1-weighted image shows extension across the cribriform plate into the anterior cranial fossa and involvement of the sphenoid sinus.
A: sinonasal undifferentiated carcinoma
Q: Sinonasal Undifferentiated Carcinoma
- Clinical: Common presenting symptoms of [...] include nasal obstruction, sinusitis, epistaxis, and/or headache.
- Micro: [...] is characterized by sheets, lobules, nests, and trabeculae of malignant cells with enlarged round nuclei and prominent nucleoli.
- Ancillary: [...] is positive for cytokeratins and may show IDH2 hotspot mutations, particularly p.R172S.
Reference Gallery:
Sinonasal undifferentiated carcinoma. Lobules, trabeculae, and nests of malignant epithelial cells.
Sinonasal undifferentiated carcinoma. Invasion into bone by tumour cells and abundant necrosis.
Sinonasal undifferentiated carcinoma. Undifferentiated tumour cell population showing a high N:C ratio, an open or vesicular chromatin pattern, and prominent nucleoli.
Sinonasal undifferentiated carcinoma. Tumour showing more basaloid morphology.
Sinonasal undifferentiated carcinoma. IDH2 p.R172S showing granular cytoplasmic staining for a multispecific antibody for mutant IDH1/2 p.R132/172 (clone MsMab-1).
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This coronal short-tau inversion recovery (STIR) image demonstrates an intermediate-signal tumour, high-signal secretions in the obstructed left maxillary sinus, and vasogenic oedema in the left frontal lobe.
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This coronal postcontrast fat-suppressed T1-weighted image shows the extent of the tumour and its proximity to the left optic nerve.
Sinonasal undifferentiated carcinoma. MRI shows a large tumour mass centred on the left ethmoid air cells, with orbital and intracranial extension. This sagittal postcontrast T1-weighted image shows extension across the cribriform plate into the anterior cranial fossa and involvement of the sphenoid sinus.
A: Sinonasal Undifferentiated Carcinoma; Sinonasal Undifferentiated Carcinoma; Sinonasal Undifferentiated Carcinoma

Q: In SWI/SNF Complex-Deficient Sinonasal Carcinoma, the SMARCB1-deficient subtype often displays a plasmacytoid/rhabdoid or basaloid morphology and is definitively diagnosed by [...] on immunohistochemistry (with retained expression in non-neoplastic cells).
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient carcinoma. High-grade tumour cells with a rhabdoid morphology.
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient carcinoma. On immunohistochemistry, the tumour cells show loss of SMARCB1 staining, whereas the stromal cells, endothelial cells, and lymphocytes retain nuclear expression.
A: complete loss of SMARCB1
Back Extra: SWI/SNF Complex-Deficient Sinonasal Carcinoma
- Clinical: Most patients present with locally advanced disease (T4), including involvement of the orbit and skull base, and symptoms are nonspecific (nasal obstruction, sinusitis, epistaxis, and headache).
- Micro: SMARCB1-deficient carcinomas display a monomorphic, predominantly basaloid or plasmacytoid/rhabdoid cell morphology, while SMARCA4-deficient carcinomas are histologically undifferentiated, composed of large epithelioid anaplastic cells.
- Ancillary: Complete loss of SMARCB1 or SMARCA4 by immunohistochemistry is required for diagnosis, and these tumours lack squamous and glandular differentiation by immunohistochemistry.
Reference Gallery:
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient carcinoma. High-grade tumour cells with a rhabdoid morphology.
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient carcinoma. Anastomosing islands of tumour cells with vesicular nuclei, conspicuous nucleoli, and moderate amounts of cytoplasm.
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient carcinoma. On immunohistochemistry, the tumour cells show loss of SMARCB1 staining, whereas the stromal cells, endothelial cells, and lymphocytes retain nuclear expression.
SMI/SNF complex–deficient sinonasal carcinoma: SMARCA4-deficient sinonasal carcinoma. Complete loss of SMARCA4 limited to the neoplastic cells.
SMI/SNF complex–deficient sinonasal carcinoma: SMARCA4-deficient sinonasal carcinoma. Focal synaptophysin reactivity is common in SMARCA4-deficient sinonasal carcinoma.
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient sinonasal adenocarcinoma. Diffuse SALL4 expression in a tumour with a yolk sac–like growth pattern.
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient sinonasal adenocarcinoma. The tumour shows an exclusively yolk sac–like growth pattern.
SMI/SNF complex–deficient sinonasal carcinoma: SMARCA4-deficient sinonasal carcinoma. Large cells arranged into irregular communicating nests and strands, with a vaguely neuroendocrine appearance.

Q: In SWI/SNF Complex-Deficient Sinonasal Carcinoma, the SMARCA4-deficient subtype is composed of histologically undifferentiated, large anaplastic epithelioid cells and requires [...] on immunohistochemistry for diagnosis.
SMI/SNF complex–deficient sinonasal carcinoma: SMARCA4-deficient sinonasal carcinoma. Large cells arranged into irregular communicating nests and strands, with a vaguely neuroendocrine appearance.
SMI/SNF complex–deficient sinonasal carcinoma: SMARCA4-deficient sinonasal carcinoma. Complete loss of SMARCA4 limited to the neoplastic cells.
A: complete loss of SMARCA4
Back Extra: SWI/SNF Complex-Deficient Sinonasal Carcinoma
- Clinical: Most patients present with locally advanced disease (T4), including involvement of the orbit and skull base, and symptoms are nonspecific (nasal obstruction, sinusitis, epistaxis, and headache).
- Micro: SMARCB1-deficient carcinomas display a monomorphic, predominantly basaloid or plasmacytoid/rhabdoid cell morphology, while SMARCA4-deficient carcinomas are histologically undifferentiated, composed of large epithelioid anaplastic cells.
- Ancillary: Complete loss of SMARCB1 or SMARCA4 by immunohistochemistry is required for diagnosis, and these tumours lack squamous and glandular differentiation by immunohistochemistry.
Reference Gallery:
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient carcinoma. High-grade tumour cells with a rhabdoid morphology.
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient carcinoma. Anastomosing islands of tumour cells with vesicular nuclei, conspicuous nucleoli, and moderate amounts of cytoplasm.
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient carcinoma. On immunohistochemistry, the tumour cells show loss of SMARCB1 staining, whereas the stromal cells, endothelial cells, and lymphocytes retain nuclear expression.
SMI/SNF complex–deficient sinonasal carcinoma: SMARCA4-deficient sinonasal carcinoma. Complete loss of SMARCA4 limited to the neoplastic cells.
SMI/SNF complex–deficient sinonasal carcinoma: SMARCA4-deficient sinonasal carcinoma. Focal synaptophysin reactivity is common in SMARCA4-deficient sinonasal carcinoma.
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient sinonasal adenocarcinoma. Diffuse SALL4 expression in a tumour with a yolk sac–like growth pattern.
SMI/SNF complex–deficient sinonasal carcinoma. SMARCB1-deficient sinonasal adenocarcinoma. The tumour shows an exclusively yolk sac–like growth pattern.
SMI/SNF complex–deficient sinonasal carcinoma: SMARCA4-deficient sinonasal carcinoma. Large cells arranged into irregular communicating nests and strands, with a vaguely neuroendocrine appearance.

Q: [...] is an aggressive sinonasal tumor characterized microscopically by a mixed proliferation of epithelial, mesenchymal, and primitive neuroepithelial elements.
Teratocarcinosarcoma. Intermixed squamous epithelium with a fetal-like clear cell appearance and spindle cells embedded in chondroid and osseous matrix.
Teratocarcinosarcoma. Primitive neuroepithelium with abundant rosette formation surrounded by hypercellular fascicles of spindle cells.
Teratocarcinosarcoma. Mixed epithelial, mesenchymal, and primitive neuroepithelial elements.
A: Teratocarcinosarcoma
Teratocarcinosarcoma
- Clinical: Presenting symptoms of nasal obstruction, epistaxis, and headache often occur due to mass effect in Teratocarcinosarcoma.
- Micro: Teratocarcinosarcoma is characterized by a mix of epithelial, mesenchymal, and primitive neuroepithelial elements.
- Ancillary: Approximately 80% of Teratocarcinosarcoma cases show loss of SMARCA4 (BRG1).
Reference Gallery:
Teratocarcinosarcoma. Intermixed squamous epithelium with a fetal-like clear cell appearance and spindle cells embedded in chondroid and osseous matrix.
Teratocarcinosarcoma. Primitive neuroepithelium with abundant rosette formation surrounded by hypercellular fascicles of spindle cells.
Teratocarcinosarcoma. Primitive neuroepithelium with transition to gland-like structures.
Teratocarcinosarcoma. Loss of SMARCA4 in tumour elements including glands and neuroepithelium, with retained expression in blood vessels.
Teratocarcinosarcoma. Mixed epithelial, mesenchymal, and primitive neuroepithelial elements.
Teratocarcinosarcoma. Axial postcontrast fat-suppressed MRI showing an aggressive soft tissue mass centred on the left maxillary sinus extending through all bony margins into the nasal cavity, cheek, and retromaxillary fat.
Teratocarcinosarcoma. Avid FDG uptake was demonstrated on PET-CT.
Teratocarcinosarcoma. Despite treatment, the patient rapidly developed multiple lung lesions consistent with metastases, as seen in this axial CT image.

Q: Approximately 80% of teratocarcinosarcoma cases demonstrate immunohistochemical loss of [...] (BRG1).
Teratocarcinosarcoma. Loss of SMARCA4 in tumour elements including glands and neuroepithelium, with retained expression in blood vessels.
A: SMARCA4
Teratocarcinosarcoma
- Clinical: Presenting symptoms of nasal obstruction, epistaxis, and headache often occur due to mass effect in Teratocarcinosarcoma.
- Micro: Teratocarcinosarcoma is characterized by a mix of epithelial, mesenchymal, and primitive neuroepithelial elements.
- Ancillary: Approximately 80% of Teratocarcinosarcoma cases show loss of SMARCA4 (BRG1).
Reference Gallery:
Teratocarcinosarcoma. Intermixed squamous epithelium with a fetal-like clear cell appearance and spindle cells embedded in chondroid and osseous matrix.
Teratocarcinosarcoma. Primitive neuroepithelium with abundant rosette formation surrounded by hypercellular fascicles of spindle cells.
Teratocarcinosarcoma. Primitive neuroepithelium with transition to gland-like structures.
Teratocarcinosarcoma. Loss of SMARCA4 in tumour elements including glands and neuroepithelium, with retained expression in blood vessels.
Teratocarcinosarcoma. Mixed epithelial, mesenchymal, and primitive neuroepithelial elements.
Teratocarcinosarcoma. Axial postcontrast fat-suppressed MRI showing an aggressive soft tissue mass centred on the left maxillary sinus extending through all bony margins into the nasal cavity, cheek, and retromaxillary fat.
Teratocarcinosarcoma. Avid FDG uptake was demonstrated on PET-CT.
Teratocarcinosarcoma. Despite treatment, the patient rapidly developed multiple lung lesions consistent with metastases, as seen in this axial CT image.

Q: Nasal Chondromesenchymal Hamartoma presents as a destructive sinonasal mass (typically in infants) and is commonly associated with mutations in the [...] gene.
Nasal chondromesenchymal hamartoma. A coronal CT image showing a destructive sinonasal tract mass with intracranial extension.
A: DICER1
Back Extra: Nasal Chondromesenchymal Hamartoma
- Clinical: Nasal chondromesenchymal hamartomas are typically identified as nonspecific masses in children, with a peak incidence in those under 1 year of age.
- Micro: The lesion is characterized by cysts lined by respiratory epithelium, immature to mature cartilage, and a variably myxoid spindle cell stroma.
- Ancillary: Immunohistochemistry shows S100 positivity in the cartilaginous areas, and DICER1 mutations are commonly identified in these tumors.
Reference Gallery:
Nasal chondromesenchymal hamartoma. A coronal CT image showing a destructive sinonasal tract mass with intracranial extension.
Nasal chondromesenchymal hamartoma. Low-power view shows immature cartilage and stroma in a background of minor mucoserous glands.
Nasal chondromesenchymal hamartoma. Intermediate-power view demonstrating immature islands of cartilage in a cellular background stroma.
Nasal chondromesenchymal hamartoma. High-power view shows immature cartilage in a cellular stroma showing mild nuclear pleomorphism. Extravasated erythrocytes are noted, with focal cystic changes.
Nasal chondromesenchymal hamartoma. Bone, immature cartilage, and a cellular spindled cell stroma are noted in this hamartoma.
Nasal chondromesenchymal hamartoma. S100 strongly highlights the nuclei and cytoplasm of the cartilaginous portions of the hamartoma. (The minor mucoserous gland is a good internal control.)

Q: The characteristic histologic appearance of Nasal Chondromesenchymal Hamartoma includes a cellular, variably myxoid spindle cell stroma admixed with focal cysts and islands of immature to mature [...].
Nasal chondromesenchymal hamartoma. Intermediate-power view demonstrating immature islands of cartilage in a cellular background stroma.
Nasal chondromesenchymal hamartoma. Bone, immature cartilage, and a cellular spindled cell stroma are noted in this hamartoma.
A: cartilage
Back Extra: Nasal Chondromesenchymal Hamartoma
- Clinical: Nasal chondromesenchymal hamartomas are typically identified as nonspecific masses in children, with a peak incidence in those under 1 year of age.
- Micro: The lesion is characterized by cysts lined by respiratory epithelium, immature to mature cartilage, and a variably myxoid spindle cell stroma.
- Ancillary: Immunohistochemistry shows S100 positivity in the cartilaginous areas, and DICER1 mutations are commonly identified in these tumors.
Reference Gallery:
Nasal chondromesenchymal hamartoma. A coronal CT image showing a destructive sinonasal tract mass with intracranial extension.
Nasal chondromesenchymal hamartoma. Low-power view shows immature cartilage and stroma in a background of minor mucoserous glands.
Nasal chondromesenchymal hamartoma. Intermediate-power view demonstrating immature islands of cartilage in a cellular background stroma.
Nasal chondromesenchymal hamartoma. High-power view shows immature cartilage in a cellular stroma showing mild nuclear pleomorphism. Extravasated erythrocytes are noted, with focal cystic changes.
Nasal chondromesenchymal hamartoma. Bone, immature cartilage, and a cellular spindled cell stroma are noted in this hamartoma.
Nasal chondromesenchymal hamartoma. S100 strongly highlights the nuclei and cytoplasm of the cartilaginous portions of the hamartoma. (The minor mucoserous gland is a good internal control.)

Q: In Nasal Chondromesenchymal Hamartoma, the characteristic islands of immature matrix are strongly positive for the immunohistochemical marker [...].
Nasal chondromesenchymal hamartoma. S100 strongly highlights the nuclei and cytoplasm of the cartilaginous portions of the hamartoma. (The minor mucoserous gland is a good internal control.)
A: S100
Back Extra: Nasal Chondromesenchymal Hamartoma
- Clinical: Nasal chondromesenchymal hamartomas are typically identified as nonspecific masses in children, with a peak incidence in those under 1 year of age.
- Micro: The lesion is characterized by cysts lined by respiratory epithelium, immature to mature cartilage, and a variably myxoid spindle cell stroma.
- Ancillary: Immunohistochemistry shows S100 positivity in the cartilaginous areas, and DICER1 mutations are commonly identified in these tumors.
Reference Gallery:
Nasal chondromesenchymal hamartoma. A coronal CT image showing a destructive sinonasal tract mass with intracranial extension.
Nasal chondromesenchymal hamartoma. Low-power view shows immature cartilage and stroma in a background of minor mucoserous glands.
Nasal chondromesenchymal hamartoma. Intermediate-power view demonstrating immature islands of cartilage in a cellular background stroma.
Nasal chondromesenchymal hamartoma. High-power view shows immature cartilage in a cellular stroma showing mild nuclear pleomorphism. Extravasated erythrocytes are noted, with focal cystic changes.
Nasal chondromesenchymal hamartoma. Bone, immature cartilage, and a cellular spindled cell stroma are noted in this hamartoma.
Nasal chondromesenchymal hamartoma. S100 strongly highlights the nuclei and cytoplasm of the cartilaginous portions of the hamartoma. (The minor mucoserous gland is a good internal control.)

Q: Histologically, [...] typically presents as a nasal polypoid mass consisting of elongated or ovoid glands lined by pseudostratified ciliated epithelium and surrounded by a thick, hyalinized stroma.
Respiratory epithelial adenomatoid hamartoma. Polypoid mass consisting of elongated or ovoid glands, descending from the surface.
Respiratory epithelial adenomatoid hamartoma. Glands are lined by ciliated epithelium with mucinous cells, enveloped by thick, hyalinized stroma. There is intervening chronic inflammation.
A: Respiratory Epithelial Adenomatoid Hamartoma
Q: Respiratory Epithelial Adenomatoid Hamartoma
- Clinical: Patients with [...] may present with nasal obstruction, anosmia, headache, and epistaxis, often in the context of chronic rhinosinusitis.
- Micro: [...] consists of elongated or ovoid glands lined by pseudostratified, ciliated epithelium with mucinous metaplasia, surrounded by a thickened basement membrane.
- Ancillary: Immunohistochemistry for [...] shows staining for CK7, MUC4, and CK8/18, but not for CK5/6, CK20, CDX2, or SATB2.
Reference Gallery:
Respiratory epithelial adenomatoid hamartoma. Polypoid mass consisting of elongated or ovoid glands, descending from the surface.
Respiratory epithelial adenomatoid hamartoma. Marked stromal hyalinization with flattening of the epithelium is common.
Respiratory epithelial adenomatoid hamartoma. Glands are lined by ciliated epithelium with mucinous cells, enveloped by thick, hyalinized stroma. There is intervening chronic inflammation.
Respiratory epithelial adenomatoid hamartoma. In most cases, collections of small seromucinous glands are also noted between the larger glands.
Respiratory epithelial adenomatoid hamartoma, chondro-osseous and respiratory epithelial subtype. This lesion consists of a proliferation of small surface-type and seromucinous glands, associated with spicules of mature lamellar bone.
A: Respiratory Epithelial Adenomatoid Hamartoma; Respiratory Epithelial Adenomatoid Hamartoma; Respiratory Epithelial Adenomatoid Hamartoma

Q: A characteristic histologic feature of Respiratory Epithelial Adenomatoid Hamartoma is the presence of elongated, descending glands enveloped by a distinctly thickened and [...] (or basement membrane).
Respiratory epithelial adenomatoid hamartoma. Marked stromal hyalinization with flattening of the epithelium is common.
Respiratory epithelial adenomatoid hamartoma. Glands are lined by ciliated epithelium with mucinous cells, enveloped by thick, hyalinized stroma. There is intervening chronic inflammation.
A: hyalinized stroma
Q: Respiratory Epithelial Adenomatoid Hamartoma
- Clinical: Patients with [...] may present with nasal obstruction, anosmia, headache, and epistaxis, often in the context of chronic rhinosinusitis.
- Micro: [...] consists of elongated or ovoid glands lined by pseudostratified, ciliated epithelium with mucinous metaplasia, surrounded by a thickened basement membrane.
- Ancillary: Immunohistochemistry for [...] shows staining for CK7, MUC4, and CK8/18, but not for CK5/6, CK20, CDX2, or SATB2.
Reference Gallery:
Respiratory epithelial adenomatoid hamartoma. Polypoid mass consisting of elongated or ovoid glands, descending from the surface.
Respiratory epithelial adenomatoid hamartoma. Marked stromal hyalinization with flattening of the epithelium is common.
Respiratory epithelial adenomatoid hamartoma. Glands are lined by ciliated epithelium with mucinous cells, enveloped by thick, hyalinized stroma. There is intervening chronic inflammation.
Respiratory epithelial adenomatoid hamartoma. In most cases, collections of small seromucinous glands are also noted between the larger glands.
Respiratory epithelial adenomatoid hamartoma, chondro-osseous and respiratory epithelial subtype. This lesion consists of a proliferation of small surface-type and seromucinous glands, associated with spicules of mature lamellar bone.
A: Respiratory Epithelial Adenomatoid Hamartoma; Respiratory Epithelial Adenomatoid Hamartoma; Respiratory Epithelial Adenomatoid Hamartoma

Q: The chondro-osseous subtype of Respiratory Epithelial Adenomatoid Hamartoma consists of a proliferation of small surface-type and seromucinous glands intimately associated with spicules of mature [...].
Respiratory epithelial adenomatoid hamartoma, chondro-osseous and respiratory epithelial subtype. This lesion consists of a proliferation of small surface-type and seromucinous glands, associated with spicules of mature lamellar bone.
A: lamellar bone
Q: Respiratory Epithelial Adenomatoid Hamartoma
- Clinical: Patients with [...] may present with nasal obstruction, anosmia, headache, and epistaxis, often in the context of chronic rhinosinusitis.
- Micro: [...] consists of elongated or ovoid glands lined by pseudostratified, ciliated epithelium with mucinous metaplasia, surrounded by a thickened basement membrane.
- Ancillary: Immunohistochemistry for [...] shows staining for CK7, MUC4, and CK8/18, but not for CK5/6, CK20, CDX2, or SATB2.
Reference Gallery:
Respiratory epithelial adenomatoid hamartoma. Polypoid mass consisting of elongated or ovoid glands, descending from the surface.
Respiratory epithelial adenomatoid hamartoma. Marked stromal hyalinization with flattening of the epithelium is common.
Respiratory epithelial adenomatoid hamartoma. Glands are lined by ciliated epithelium with mucinous cells, enveloped by thick, hyalinized stroma. There is intervening chronic inflammation.
Respiratory epithelial adenomatoid hamartoma. In most cases, collections of small seromucinous glands are also noted between the larger glands.
Respiratory epithelial adenomatoid hamartoma, chondro-osseous and respiratory epithelial subtype. This lesion consists of a proliferation of small surface-type and seromucinous glands, associated with spicules of mature lamellar bone.
A: Respiratory Epithelial Adenomatoid Hamartoma; Respiratory Epithelial Adenomatoid Hamartoma; Respiratory Epithelial Adenomatoid Hamartoma

Q: Microscopically, Seromucinous Hamartoma is characteristically a polypoid lesion that features a proliferation of small, eosinophilic glands arranged in a [...] distribution within the stroma.
Seromucinous hamartoma. The lesion is polypoid and contains many small glands in the stroma, with a horizontal/lobular distribution.
Seromucinous hamartoma. Glands are small, eosinophilic, and uniform, and they may contain an amorphous eosinophilic material. Basal lamina around tubules is discernible.
A: horizontal or lobular
Back Extra: Seromucinous Hamartoma
- Clinical: Seromucinous hamartoma presents with nasal obstruction, purulent rhinorrhoea, and epistaxis.
- Micro: The lesion is characterized by small, eosinophilic glands in a polypoid structure, often with a horizontal/lobular distribution.
- Ancillary: Immunohistochemistry shows S100 positivity in the glands and absence of p63-positive basal cells around small glands.
Reference Gallery:
Seromucinous hamartoma. The lesion is polypoid and contains many small glands in the stroma, with a horizontal/lobular distribution.
Seromucinous hamartoma. Glands are small, eosinophilic, and uniform, and they may contain an amorphous eosinophilic material. Basal lamina around tubules is discernible.
Seromucinous hamartoma. Glands are immunoreactive for S100.
Seromucinous hamartoma. p63-positive basal cells are absent around small glands but are evident around cystic structures lined by respiratory epithelium.
Seromucinous hamartoma. Small eosinophilic glands may be admixed with cystic structures lined by respiratory epithelium.

Q: In Seromucinous Hamartoma, immunohistochemical staining reveals that the small, uniform glands are characteristically positive for [...].
Seromucinous hamartoma. Glands are immunoreactive for S100.
A: S100
Back Extra: Seromucinous Hamartoma
- Clinical: Seromucinous hamartoma presents with nasal obstruction, purulent rhinorrhoea, and epistaxis.
- Micro: The lesion is characterized by small, eosinophilic glands in a polypoid structure, often with a horizontal/lobular distribution.
- Ancillary: Immunohistochemistry shows S100 positivity in the glands and absence of p63-positive basal cells around small glands.
Reference Gallery:
Seromucinous hamartoma. The lesion is polypoid and contains many small glands in the stroma, with a horizontal/lobular distribution.
Seromucinous hamartoma. Glands are small, eosinophilic, and uniform, and they may contain an amorphous eosinophilic material. Basal lamina around tubules is discernible.
Seromucinous hamartoma. Glands are immunoreactive for S100.
Seromucinous hamartoma. p63-positive basal cells are absent around small glands but are evident around cystic structures lined by respiratory epithelium.
Seromucinous hamartoma. Small eosinophilic glands may be admixed with cystic structures lined by respiratory epithelium.

Q: A key immunohistochemical feature of Seromucinous Hamartoma is the absence of [...]-positive basal cells around the small eosinophilic glands, though they remain evident around larger cystic structures.
Seromucinous hamartoma. p63-positive basal cells are absent around small glands but are evident around cystic structures lined by respiratory epithelium.
Seromucinous hamartoma. Small eosinophilic glands may be admixed with cystic structures lined by respiratory epithelium.
A: p63
Back Extra: Seromucinous Hamartoma
- Clinical: Seromucinous hamartoma presents with nasal obstruction, purulent rhinorrhoea, and epistaxis.
- Micro: The lesion is characterized by small, eosinophilic glands in a polypoid structure, often with a horizontal/lobular distribution.
- Ancillary: Immunohistochemistry shows S100 positivity in the glands and absence of p63-positive basal cells around small glands.
Reference Gallery:
Seromucinous hamartoma. The lesion is polypoid and contains many small glands in the stroma, with a horizontal/lobular distribution.
Seromucinous hamartoma. Glands are small, eosinophilic, and uniform, and they may contain an amorphous eosinophilic material. Basal lamina around tubules is discernible.
Seromucinous hamartoma. Glands are immunoreactive for S100.
Seromucinous hamartoma. p63-positive basal cells are absent around small glands but are evident around cystic structures lined by respiratory epithelium.
Seromucinous hamartoma. Small eosinophilic glands may be admixed with cystic structures lined by respiratory epithelium.

Q: Biphenotypic Sinonasal Sarcoma is characterized microscopically by a densely cellular spindle cell proliferation forming long fascicles with characteristic [...].
Biphenotypic sinonasal sarcoma. The tumour exhibits a densely cellular spindle cell proliferation forming long fascicles with entrapped epithelial foci.
Biphenotypic sinonasal sarcoma. Densely cellular spindle cell proliferations forming long fascicles with entrapped epithelial foci.
A: entrapped epithelial foci
Back Extra: Biphenotypic Sinonasal Sarcoma
- Clinical: Biphenotypic sinonasal sarcoma often presents with nasal obstruction, pain, epistaxis, or rhinorrhoea, and is more common in females with a mean age of 53 years.
- Micro: The microscopic appearance of biphenotypic sinonasal sarcoma includes a densely cellular spindle cell proliferation forming long fascicles, with entrapped epithelial foci and a low mitotic rate.
- Ancillary: Ancillary studies show that biphenotypic sinonasal sarcoma is consistently positive for PAX3 and SMA, and negative for SOX10. Desmin and MYOD1 staining are inconsistent and often patchy or focal.
Reference Gallery:
Biphenotypic sinonasal sarcoma. Diffuse nuclear PAX3 staining (using clone 274212).
Biphenotypic sinonasal sarcoma. Coronal CT. The tumour is seen infiltrating the left maxillary sinus, ethmoid sinus, and left nasal cavity.
Biphenotypic sinonasal sarcoma. MRI of the left ethmoid air cells shows tumour infiltrating the orbital wall, frontal lobe, and left nasal cavity (coronal view, T1 spin echo signal, with injection of gadolinium).
Biphenotypic sinonasal sarcoma. MRI picture of a tumour of the left maxillary sinus infiltrating the left nasal cavity (T2 fast spin echo signal with fat saturation).
Biphenotypic sinonasal sarcoma. The tumour exhibits a densely cellular spindle cell proliferation forming long fascicles with entrapped epithelial foci.
Biphenotypic sinonasal sarcoma. Densely cellular spindle cell proliferations forming long fascicles with entrapped epithelial foci.
Biphenotypic sinonasal sarcoma. The tumour cells display monotonous elongated nuclei with fine chromatin and low mitotic activity.
Biphenotypic sinonasal sarcoma. The tumour can occasionally display focal rhabdomyoblastic differentiation.
Biphenotypic sinonasal sarcoma. The tumour cells show heterogeneous staining with desmin antibody, which is most often patchy and focal (desmin immunohistochemistry).
Biphenotypic sinonasal sarcoma. The tumour cells show heterogeneous nuclear immunoreactivity of rhabdomyoblastic cells for MYOD1.
Biphenotypic sinonasal sarcoma. The tumour cells never express SOX10 (SOX10 immunohistochemistry).

Q: In terms of immunohistochemistry, Biphenotypic Sinonasal Sarcoma is consistently positive for SMA and [...], while remaining definitively negative for SOX10.
Biphenotypic sinonasal sarcoma. Diffuse nuclear PAX3 staining (using clone 274212).
Biphenotypic sinonasal sarcoma. The tumour cells never express SOX10 (SOX10 immunohistochemistry).
A: PAX3
Back Extra: Biphenotypic Sinonasal Sarcoma
- Clinical: Biphenotypic sinonasal sarcoma often presents with nasal obstruction, pain, epistaxis, or rhinorrhoea, and is more common in females with a mean age of 53 years.
- Micro: The microscopic appearance of biphenotypic sinonasal sarcoma includes a densely cellular spindle cell proliferation forming long fascicles, with entrapped epithelial foci and a low mitotic rate.
- Ancillary: Ancillary studies show that biphenotypic sinonasal sarcoma is consistently positive for PAX3 and SMA, and negative for SOX10. Desmin and MYOD1 staining are inconsistent and often patchy or focal.
Reference Gallery:
Biphenotypic sinonasal sarcoma. Diffuse nuclear PAX3 staining (using clone 274212).
Biphenotypic sinonasal sarcoma. Coronal CT. The tumour is seen infiltrating the left maxillary sinus, ethmoid sinus, and left nasal cavity.
Biphenotypic sinonasal sarcoma. MRI of the left ethmoid air cells shows tumour infiltrating the orbital wall, frontal lobe, and left nasal cavity (coronal view, T1 spin echo signal, with injection of gadolinium).
Biphenotypic sinonasal sarcoma. MRI picture of a tumour of the left maxillary sinus infiltrating the left nasal cavity (T2 fast spin echo signal with fat saturation).
Biphenotypic sinonasal sarcoma. The tumour exhibits a densely cellular spindle cell proliferation forming long fascicles with entrapped epithelial foci.
Biphenotypic sinonasal sarcoma. Densely cellular spindle cell proliferations forming long fascicles with entrapped epithelial foci.
Biphenotypic sinonasal sarcoma. The tumour cells display monotonous elongated nuclei with fine chromatin and low mitotic activity.
Biphenotypic sinonasal sarcoma. The tumour can occasionally display focal rhabdomyoblastic differentiation.
Biphenotypic sinonasal sarcoma. The tumour cells show heterogeneous staining with desmin antibody, which is most often patchy and focal (desmin immunohistochemistry).
Biphenotypic sinonasal sarcoma. The tumour cells show heterogeneous nuclear immunoreactivity of rhabdomyoblastic cells for MYOD1.
Biphenotypic sinonasal sarcoma. The tumour cells never express SOX10 (SOX10 immunohistochemistry).

Q: A cellular spindle cell tumor of the nasal cavity that often demonstrates focal rhabdomyoblastic differentiation with patchy desmin and MYOD1 expression is diagnostic of [...].
Biphenotypic sinonasal sarcoma. The tumour can occasionally display focal rhabdomyoblastic differentiation.
Biphenotypic sinonasal sarcoma. The tumour cells show heterogeneous staining with desmin antibody, which is most often patchy and focal (desmin immunohistochemistry).
Biphenotypic sinonasal sarcoma. The tumour cells show heterogeneous nuclear immunoreactivity of rhabdomyoblastic cells for MYOD1.
A: Biphenotypic Sinonasal Sarcoma
Back Extra: Biphenotypic Sinonasal Sarcoma
- Clinical: Biphenotypic sinonasal sarcoma often presents with nasal obstruction, pain, epistaxis, or rhinorrhoea, and is more common in females with a mean age of 53 years.
- Micro: The microscopic appearance of biphenotypic sinonasal sarcoma includes a densely cellular spindle cell proliferation forming long fascicles, with entrapped epithelial foci and a low mitotic rate.
- Ancillary: Ancillary studies show that biphenotypic sinonasal sarcoma is consistently positive for PAX3 and SMA, and negative for SOX10. Desmin and MYOD1 staining are inconsistent and often patchy or focal.
Reference Gallery:
Biphenotypic sinonasal sarcoma. Diffuse nuclear PAX3 staining (using clone 274212).
Biphenotypic sinonasal sarcoma. Coronal CT. The tumour is seen infiltrating the left maxillary sinus, ethmoid sinus, and left nasal cavity.
Biphenotypic sinonasal sarcoma. MRI of the left ethmoid air cells shows tumour infiltrating the orbital wall, frontal lobe, and left nasal cavity (coronal view, T1 spin echo signal, with injection of gadolinium).
Biphenotypic sinonasal sarcoma. MRI picture of a tumour of the left maxillary sinus infiltrating the left nasal cavity (T2 fast spin echo signal with fat saturation).
Biphenotypic sinonasal sarcoma. The tumour exhibits a densely cellular spindle cell proliferation forming long fascicles with entrapped epithelial foci.
Biphenotypic sinonasal sarcoma. Densely cellular spindle cell proliferations forming long fascicles with entrapped epithelial foci.
Biphenotypic sinonasal sarcoma. The tumour cells display monotonous elongated nuclei with fine chromatin and low mitotic activity.
Biphenotypic sinonasal sarcoma. The tumour can occasionally display focal rhabdomyoblastic differentiation.
Biphenotypic sinonasal sarcoma. The tumour cells show heterogeneous staining with desmin antibody, which is most often patchy and focal (desmin immunohistochemistry).
Biphenotypic sinonasal sarcoma. The tumour cells show heterogeneous nuclear immunoreactivity of rhabdomyoblastic cells for MYOD1.
Biphenotypic sinonasal sarcoma. The tumour cells never express SOX10 (SOX10 immunohistochemistry).

Q: A classic histologic feature of Chordoma is the presence of large epithelioid cells with bubbly cytoplasm known as [...], which are typically embedded in a myxoid or chondroid matrix.
Chordoma. Physaliphorous cells are quite characteristic of chordoma, where there are numerous vacuolations in the cytoplasm that result in a spider-like appearance.
Chordoma. Cellular smear with large cells containing cytoplasmic vacuoles set within a magenta matrix material (Giemsa).
A: physaliphorous cells
Back Extra: Chordoma
- Clinical: Chordoma presents with pain, a mass lesion, and neurological deficits. Commonly seen in the nasopharynx and skull base, it is rare in Black patients and has a male predominance.
- Micro: Characterized by large epithelioid cells with bubbly cytoplasm (physaliphorous cells) embedded in a myxoid or chondroid matrix. Poorly differentiated chordoma lacks the myxoid matrix and shows pleomorphic epithelioid cells with areas of rhabdoid morphology.
- Ancillary: Neoplastic cells are strongly positive for cytokeratin, EMA, and brachyury (TBXT). Poorly differentiated chordoma shows loss of SMARCB1 expression.
Reference Gallery:
Chordoma. Sagittal CT demonstrates a large, destructive, soft tissue–density mass within the nasopharynx and skull base.
Chordoma. This sagittal T2-weighted image shows a hyperintense, destructive, nasopharynx midline mass.
Chordoma. Physaliphorous cells are quite characteristic of chordoma, where there are numerous vacuolations in the cytoplasm that result in a spider-like appearance.
Chordoma. There is strong, diffuse nuclear expression of brachyury in the neoplastic cells of chordoma.
Chordoma. Small groups of cells clustered together in a myxoid-mucinous matrix. Note the large signet ring–like cells along with smaller cells with granular cytoplasm (Pap-stained smear).
Chordoma. Cellular smear with large cells containing cytoplasmic vacuoles set within a magenta matrix material (Giemsa).
Chordoma. Poorly differentiated chordoma. Sheets of pleomorphic epithelioid cells. There is no myxoid matrix. Necrosis is often a feature.
Chordoma. Poorly differentiated chordoma. Characteristic loss of expression of SMARCB1.

Q: The neoplastic cells of Chordoma are strongly and characteristically positive for the nuclear transcription factor [...] (TBXT) by immunohistochemistry.
Chordoma. There is strong, diffuse nuclear expression of brachyury in the neoplastic cells of chordoma.
A: brachyury
Back Extra: Chordoma
- Clinical: Chordoma presents with pain, a mass lesion, and neurological deficits. Commonly seen in the nasopharynx and skull base, it is rare in Black patients and has a male predominance.
- Micro: Characterized by large epithelioid cells with bubbly cytoplasm (physaliphorous cells) embedded in a myxoid or chondroid matrix. Poorly differentiated chordoma lacks the myxoid matrix and shows pleomorphic epithelioid cells with areas of rhabdoid morphology.
- Ancillary: Neoplastic cells are strongly positive for cytokeratin, EMA, and brachyury (TBXT). Poorly differentiated chordoma shows loss of SMARCB1 expression.
Reference Gallery:
Chordoma. Sagittal CT demonstrates a large, destructive, soft tissue–density mass within the nasopharynx and skull base.
Chordoma. This sagittal T2-weighted image shows a hyperintense, destructive, nasopharynx midline mass.
Chordoma. Physaliphorous cells are quite characteristic of chordoma, where there are numerous vacuolations in the cytoplasm that result in a spider-like appearance.
Chordoma. There is strong, diffuse nuclear expression of brachyury in the neoplastic cells of chordoma.
Chordoma. Small groups of cells clustered together in a myxoid-mucinous matrix. Note the large signet ring–like cells along with smaller cells with granular cytoplasm (Pap-stained smear).
Chordoma. Cellular smear with large cells containing cytoplasmic vacuoles set within a magenta matrix material (Giemsa).
Chordoma. Poorly differentiated chordoma. Sheets of pleomorphic epithelioid cells. There is no myxoid matrix. Necrosis is often a feature.
Chordoma. Poorly differentiated chordoma. Characteristic loss of expression of SMARCB1.

Q: Poorly differentiated Chordoma, which lacks a myxoid matrix and shows pleomorphic epithelioid cells, characteristically demonstrates a loss of [...] expression by immunohistochemistry.
Chordoma. Poorly differentiated chordoma. Sheets of pleomorphic epithelioid cells. There is no myxoid matrix. Necrosis is often a feature.
Chordoma. Poorly differentiated chordoma. Characteristic loss of expression of SMARCB1.
A: SMARCB1
Back Extra: Chordoma
- Clinical: Chordoma presents with pain, a mass lesion, and neurological deficits. Commonly seen in the nasopharynx and skull base, it is rare in Black patients and has a male predominance.
- Micro: Characterized by large epithelioid cells with bubbly cytoplasm (physaliphorous cells) embedded in a myxoid or chondroid matrix. Poorly differentiated chordoma lacks the myxoid matrix and shows pleomorphic epithelioid cells with areas of rhabdoid morphology.
- Ancillary: Neoplastic cells are strongly positive for cytokeratin, EMA, and brachyury (TBXT). Poorly differentiated chordoma shows loss of SMARCB1 expression.
Reference Gallery:
Chordoma. Sagittal CT demonstrates a large, destructive, soft tissue–density mass within the nasopharynx and skull base.
Chordoma. This sagittal T2-weighted image shows a hyperintense, destructive, nasopharynx midline mass.
Chordoma. Physaliphorous cells are quite characteristic of chordoma, where there are numerous vacuolations in the cytoplasm that result in a spider-like appearance.
Chordoma. There is strong, diffuse nuclear expression of brachyury in the neoplastic cells of chordoma.
Chordoma. Small groups of cells clustered together in a myxoid-mucinous matrix. Note the large signet ring–like cells along with smaller cells with granular cytoplasm (Pap-stained smear).
Chordoma. Cellular smear with large cells containing cytoplasmic vacuoles set within a magenta matrix material (Giemsa).
Chordoma. Poorly differentiated chordoma. Sheets of pleomorphic epithelioid cells. There is no myxoid matrix. Necrosis is often a feature.
Chordoma. Poorly differentiated chordoma. Characteristic loss of expression of SMARCB1.

Q: A characteristic histologic finding in Sinonasal Glomangiopericytoma is a complex vascular network with open, patulous [...] vessels and peritheliomatous hyalinization.
Sinonasal glomangiopericytoma. Open, patulous vessels with a staghorn or antler-like configuration are characteristic of the tumour.
Sinonasal glomangiopericytoma. A peritheliomatous hyalinization with a patternless proliferation of ovoid to spindled cells is a characteristic finding of the tumour.
A: staghorn
Back Extra: Sinonasal Glomangiopericytoma
- Clinical: Sinonasal glomangiopericytomas most commonly present with nasal obstruction and epistaxis, affecting patients in the sixth to seventh decades of life with a slight female predilection.
- Micro: The tumour shows a complex, ramifying vascular network with characteristic staghorn vessels and peritheliomatous hyalinization, with spindle-shaped to ovoid cells and syncytial arrangement.
- Ancillary: Immunohistochemistry shows strong positivity for SMA and nuclear β-catenin, with recurrent missense mutations in CTNNB1 exon 3, particularly at codon 33.
Reference Gallery:
Sinonasal glomangiopericytoma. CT shows a large, polypoid, soft tissue–density mass filling the nasal cavity and extending into the nasopharynx.
Sinonasal glomangiopericytoma. T1-weighted, fat-suppressed, postcontrast axial MRI shows an enhancing mass within the nasal cavity and adjacent sinuses.
Sinonasal glomangiopericytoma. An intact respiratory lining covers a cellular neoplastic proliferation with short, interlacing fascicles.
Sinonasal glomangiopericytoma. The spindled cell neoplasm is separated from the surface epithelium by a well-developed zone of fibrosis.
Sinonasal glomangiopericytoma. Open, patulous vessels with a staghorn or antler-like configuration are characteristic of the tumour.
Sinonasal glomangiopericytoma. A peritheliomatous hyalinization with a patternless proliferation of ovoid to spindled cells is a characteristic finding of the tumour.
Sinonasal glomangiopericytoma. Tumours show a variable cellularity, with a high cellularity seen in this tumour. Note the syncytial quality to the neoplastic cells.
Sinonasal glomangiopericytoma. Cellularity can be quite variable, with this field demonstrating a hypocellular area, where the neoplastic cells are spindled with a cleared cytoplasm.
Sinonasal glomangiopericytoma. A reticulated pattern shows open spaces with extravasated erythrocytes along with large, patulous vascular spaces.
Sinonasal glomangiopericytoma. Tumour cells are isomorphic, with bland, monotonous nuclei with fine chromatin distribution. Eosinophils and mast cells are commonly present.
Sinonasal glomangiopericytoma. Marked erythrocyte extravasation into the tumour may obscure the true nature of the neoplasm.
Sinonasal glomangiopericytoma. The neoplastic cells demonstrate a diffuse cytoplasmic reaction for SMA, a feature characteristic of this tumour.

Q: Immunohistochemistry in Sinonasal Glomangiopericytoma characteristically exhibits a diffuse cytoplasmic reaction for [...] along with nuclear expression of β-catenin.
Sinonasal glomangiopericytoma. The neoplastic cells demonstrate a diffuse cytoplasmic reaction for SMA, a feature characteristic of this tumour.
A: SMA
Back Extra: Sinonasal Glomangiopericytoma
- Clinical: Sinonasal glomangiopericytomas most commonly present with nasal obstruction and epistaxis, affecting patients in the sixth to seventh decades of life with a slight female predilection.
- Micro: The tumour shows a complex, ramifying vascular network with characteristic staghorn vessels and peritheliomatous hyalinization, with spindle-shaped to ovoid cells and syncytial arrangement.
- Ancillary: Immunohistochemistry shows strong positivity for SMA and nuclear β-catenin, with recurrent missense mutations in CTNNB1 exon 3, particularly at codon 33.
Reference Gallery:
Sinonasal glomangiopericytoma. CT shows a large, polypoid, soft tissue–density mass filling the nasal cavity and extending into the nasopharynx.
Sinonasal glomangiopericytoma. T1-weighted, fat-suppressed, postcontrast axial MRI shows an enhancing mass within the nasal cavity and adjacent sinuses.
Sinonasal glomangiopericytoma. An intact respiratory lining covers a cellular neoplastic proliferation with short, interlacing fascicles.
Sinonasal glomangiopericytoma. The spindled cell neoplasm is separated from the surface epithelium by a well-developed zone of fibrosis.
Sinonasal glomangiopericytoma. Open, patulous vessels with a staghorn or antler-like configuration are characteristic of the tumour.
Sinonasal glomangiopericytoma. A peritheliomatous hyalinization with a patternless proliferation of ovoid to spindled cells is a characteristic finding of the tumour.
Sinonasal glomangiopericytoma. Tumours show a variable cellularity, with a high cellularity seen in this tumour. Note the syncytial quality to the neoplastic cells.
Sinonasal glomangiopericytoma. Cellularity can be quite variable, with this field demonstrating a hypocellular area, where the neoplastic cells are spindled with a cleared cytoplasm.
Sinonasal glomangiopericytoma. A reticulated pattern shows open spaces with extravasated erythrocytes along with large, patulous vascular spaces.
Sinonasal glomangiopericytoma. Tumour cells are isomorphic, with bland, monotonous nuclei with fine chromatin distribution. Eosinophils and mast cells are commonly present.
Sinonasal glomangiopericytoma. Marked erythrocyte extravasation into the tumour may obscure the true nature of the neoplasm.
Sinonasal glomangiopericytoma. The neoplastic cells demonstrate a diffuse cytoplasmic reaction for SMA, a feature characteristic of this tumour.

Q: [...] is a spindle cell neoplasm of the nasal cavity that typically features a well-developed subepithelial zone of fibrosis and marked erythrocyte extravasation.
Sinonasal glomangiopericytoma. The spindled cell neoplasm is separated from the surface epithelium by a well-developed zone of fibrosis.
Sinonasal glomangiopericytoma. Marked erythrocyte extravasation into the tumour may obscure the true nature of the neoplasm.
A: Sinonasal Glomangiopericytoma
Back Extra: Sinonasal Glomangiopericytoma
- Clinical: Sinonasal glomangiopericytomas most commonly present with nasal obstruction and epistaxis, affecting patients in the sixth to seventh decades of life with a slight female predilection.
- Micro: The tumour shows a complex, ramifying vascular network with characteristic staghorn vessels and peritheliomatous hyalinization, with spindle-shaped to ovoid cells and syncytial arrangement.
- Ancillary: Immunohistochemistry shows strong positivity for SMA and nuclear β-catenin, with recurrent missense mutations in CTNNB1 exon 3, particularly at codon 33.
Reference Gallery:
Sinonasal glomangiopericytoma. CT shows a large, polypoid, soft tissue–density mass filling the nasal cavity and extending into the nasopharynx.
Sinonasal glomangiopericytoma. T1-weighted, fat-suppressed, postcontrast axial MRI shows an enhancing mass within the nasal cavity and adjacent sinuses.
Sinonasal glomangiopericytoma. An intact respiratory lining covers a cellular neoplastic proliferation with short, interlacing fascicles.
Sinonasal glomangiopericytoma. The spindled cell neoplasm is separated from the surface epithelium by a well-developed zone of fibrosis.
Sinonasal glomangiopericytoma. Open, patulous vessels with a staghorn or antler-like configuration are characteristic of the tumour.
Sinonasal glomangiopericytoma. A peritheliomatous hyalinization with a patternless proliferation of ovoid to spindled cells is a characteristic finding of the tumour.
Sinonasal glomangiopericytoma. Tumours show a variable cellularity, with a high cellularity seen in this tumour. Note the syncytial quality to the neoplastic cells.
Sinonasal glomangiopericytoma. Cellularity can be quite variable, with this field demonstrating a hypocellular area, where the neoplastic cells are spindled with a cleared cytoplasm.
Sinonasal glomangiopericytoma. A reticulated pattern shows open spaces with extravasated erythrocytes along with large, patulous vascular spaces.
Sinonasal glomangiopericytoma. Tumour cells are isomorphic, with bland, monotonous nuclei with fine chromatin distribution. Eosinophils and mast cells are commonly present.
Sinonasal glomangiopericytoma. Marked erythrocyte extravasation into the tumour may obscure the true nature of the neoplasm.
Sinonasal glomangiopericytoma. The neoplastic cells demonstrate a diffuse cytoplasmic reaction for SMA, a feature characteristic of this tumour.

Q: The classic clinical triad of nasal obstruction, severe epistaxis, and a highly vascular nasopharyngeal mass on imaging is characteristic of [...].
Sinonasal tract angiofibroma. Fluoroscopic angiography documents the vascular nature of the tumour, while also allowing for presurgical embolization.
Sinonasal tract angiofibroma. Axial T1-weighted MRI, postcontrast fat-saturated/suppressed T1-weighted MRI, and T2-weighted MRI images demonstrating a highly vascular soft tissue lesion in the right nasal cavity, with involvement and widening of the pterygopalatine fossa – a common finding on cross-sectional imaging. Note internal low-signal foci on the T2-weighted image denoting flow voids, as well as extension on postcontrast imaging into the pterygoid canal (Vidian canal).
A: Sinonasal Tract Angiofibroma
Back Extra: Sinonasal Tract Angiofibroma
- Clinical: The classic triad of nasal obstruction, epistaxis, and sinonasal/nasopharyngeal mass is seen in many patients, often over a prolonged symptom duration.
- Micro: The stroma is composed of bipolar or stellate fibroblastic cells with plump, vesicular, spindled nuclei and indistinct nucleoli, set within a variably cellular fibrovascular stroma.
- Ancillary: Somatic mutations in the gene encoding β-catenin (CTNNB1) are seen in 75% of tumours, and strong nuclear expression of AR and β-catenin is observed by immunohistochemistry.
Reference Gallery:
Sinonasal tract angiofibroma. Fluoroscopic angiography documents the vascular nature of the tumour, while also allowing for presurgical embolization.
Sinonasal tract angiofibroma. T1-weighted coronal MRI shows a large central destructive neoplasm. Although it is a benign tumour, it can reach a large size and be locally aggressive.
Sinonasal tract angiofibroma. The stroma may be quite cellular, with fibroblastic cells set within a collagenized stroma.
Sinonasal tract angiofibroma. The stromal cells show a strong and diffuse nuclear reaction for β-catenin by immunohistochemistry.
Sinonasal tract angiofibroma. The stromal spindled cells show a strong and diffuse nuclear reaction for AR by immunohistochemistry.
Sinonasal tract angiofibroma. The surface epithelium is unremarkable, overlying a variably cellular vascular neoplasm. Patulous vessels with and without smooth muscle walls are noted.
Sinonasal tract angiofibroma. Several vessel types are set within a fibrocollagenous stroma. There is embolic material, a finding noted after embolization.
Sinonasal tract angiofibroma. Axial T1-weighted MRI, postcontrast fat-saturated/suppressed T1-weighted MRI, and T2-weighted MRI images demonstrating a highly vascular soft tissue lesion in the right nasal cavity, with involvement and widening of the pterygopalatine fossa – a common finding on cross-sectional imaging. Note internal low-signal foci on the T2-weighted image denoting flow voids, as well as extension on postcontrast imaging into the pterygoid canal (Vidian canal).
Sinonasal tract angiofibroma. Axial postcontrast CT demonstrating a large heterogeneous, avidly enhancing soft tissue mass in the right nasal cavity involving a grossly expanded pterygopalatine fossa, filling the postnasal space and extending into adjacent parapharyngeal and masticator spaces.
Sinonasal tract angiofibroma. Axial postcontrast CT demonstrating involvement of the right sphenoid sinus and intracranial extension into the right cavernous sinus.

Q: Microscopically, [...] is characterized by a variably cellular stroma containing bipolar or stellate fibroblastic cells and patulous blood vessels with or without smooth muscle walls.
Sinonasal tract angiofibroma. The stroma may be quite cellular, with fibroblastic cells set within a collagenized stroma.
Sinonasal tract angiofibroma. The surface epithelium is unremarkable, overlying a variably cellular vascular neoplasm. Patulous vessels with and without smooth muscle walls are noted.
A: Sinonasal Tract Angiofibroma
Back Extra: Sinonasal Tract Angiofibroma
- Clinical: The classic triad of nasal obstruction, epistaxis, and sinonasal/nasopharyngeal mass is seen in many patients, often over a prolonged symptom duration.
- Micro: The stroma is composed of bipolar or stellate fibroblastic cells with plump, vesicular, spindled nuclei and indistinct nucleoli, set within a variably cellular fibrovascular stroma.
- Ancillary: Somatic mutations in the gene encoding β-catenin (CTNNB1) are seen in 75% of tumours, and strong nuclear expression of AR and β-catenin is observed by immunohistochemistry.
Reference Gallery:
Sinonasal tract angiofibroma. Fluoroscopic angiography documents the vascular nature of the tumour, while also allowing for presurgical embolization.
Sinonasal tract angiofibroma. T1-weighted coronal MRI shows a large central destructive neoplasm. Although it is a benign tumour, it can reach a large size and be locally aggressive.
Sinonasal tract angiofibroma. The stroma may be quite cellular, with fibroblastic cells set within a collagenized stroma.
Sinonasal tract angiofibroma. The stromal cells show a strong and diffuse nuclear reaction for β-catenin by immunohistochemistry.
Sinonasal tract angiofibroma. The stromal spindled cells show a strong and diffuse nuclear reaction for AR by immunohistochemistry.
Sinonasal tract angiofibroma. The surface epithelium is unremarkable, overlying a variably cellular vascular neoplasm. Patulous vessels with and without smooth muscle walls are noted.
Sinonasal tract angiofibroma. Several vessel types are set within a fibrocollagenous stroma. There is embolic material, a finding noted after embolization.
Sinonasal tract angiofibroma. Axial T1-weighted MRI, postcontrast fat-saturated/suppressed T1-weighted MRI, and T2-weighted MRI images demonstrating a highly vascular soft tissue lesion in the right nasal cavity, with involvement and widening of the pterygopalatine fossa – a common finding on cross-sectional imaging. Note internal low-signal foci on the T2-weighted image denoting flow voids, as well as extension on postcontrast imaging into the pterygoid canal (Vidian canal).
Sinonasal tract angiofibroma. Axial postcontrast CT demonstrating a large heterogeneous, avidly enhancing soft tissue mass in the right nasal cavity involving a grossly expanded pterygopalatine fossa, filling the postnasal space and extending into adjacent parapharyngeal and masticator spaces.
Sinonasal tract angiofibroma. Axial postcontrast CT demonstrating involvement of the right sphenoid sinus and intracranial extension into the right cavernous sinus.

Q: Immunohistochemistry in Sinonasal Tract Angiofibroma characteristically shows strong nuclear expression of androgen receptor (AR) and [...] (the latter due to somatic CTNNB1 mutations in most tumors).
Sinonasal tract angiofibroma. The stromal cells show a strong and diffuse nuclear reaction for β-catenin by immunohistochemistry.
Sinonasal tract angiofibroma. The stromal spindled cells show a strong and diffuse nuclear reaction for AR by immunohistochemistry.
A: beta-catenin
Back Extra: Sinonasal Tract Angiofibroma
- Clinical: The classic triad of nasal obstruction, epistaxis, and sinonasal/nasopharyngeal mass is seen in many patients, often over a prolonged symptom duration.
- Micro: The stroma is composed of bipolar or stellate fibroblastic cells with plump, vesicular, spindled nuclei and indistinct nucleoli, set within a variably cellular fibrovascular stroma.
- Ancillary: Somatic mutations in the gene encoding β-catenin (CTNNB1) are seen in 75% of tumours, and strong nuclear expression of AR and β-catenin is observed by immunohistochemistry.
Reference Gallery:
Sinonasal tract angiofibroma. Fluoroscopic angiography documents the vascular nature of the tumour, while also allowing for presurgical embolization.
Sinonasal tract angiofibroma. T1-weighted coronal MRI shows a large central destructive neoplasm. Although it is a benign tumour, it can reach a large size and be locally aggressive.
Sinonasal tract angiofibroma. The stroma may be quite cellular, with fibroblastic cells set within a collagenized stroma.
Sinonasal tract angiofibroma. The stromal cells show a strong and diffuse nuclear reaction for β-catenin by immunohistochemistry.
Sinonasal tract angiofibroma. The stromal spindled cells show a strong and diffuse nuclear reaction for AR by immunohistochemistry.
Sinonasal tract angiofibroma. The surface epithelium is unremarkable, overlying a variably cellular vascular neoplasm. Patulous vessels with and without smooth muscle walls are noted.
Sinonasal tract angiofibroma. Several vessel types are set within a fibrocollagenous stroma. There is embolic material, a finding noted after embolization.
Sinonasal tract angiofibroma. Axial T1-weighted MRI, postcontrast fat-saturated/suppressed T1-weighted MRI, and T2-weighted MRI images demonstrating a highly vascular soft tissue lesion in the right nasal cavity, with involvement and widening of the pterygopalatine fossa – a common finding on cross-sectional imaging. Note internal low-signal foci on the T2-weighted image denoting flow voids, as well as extension on postcontrast imaging into the pterygoid canal (Vidian canal).
Sinonasal tract angiofibroma. Axial postcontrast CT demonstrating a large heterogeneous, avidly enhancing soft tissue mass in the right nasal cavity involving a grossly expanded pterygopalatine fossa, filling the postnasal space and extending into adjacent parapharyngeal and masticator spaces.
Sinonasal tract angiofibroma. Axial postcontrast CT demonstrating involvement of the right sphenoid sinus and intracranial extension into the right cavernous sinus.

Q: Histologically, low-grade olfactory neuroblastoma is characterized by a prominent fibrillary matrix (neuropil) and the presence of [...].
Olfactory neuroblastoma. Hyams grade I tumour showing a lobular architecture and a prominent fibrillary matrix. Homer Wright rosettes are noted.
A: Homer Wright rosettes
Back Extra: Olfactory Neuroblastoma
- Clinical: Nasal obstruction is the most common symptom of Olfactory Neuroblastoma, often accompanied by epistaxis, nasal discharge, and/or pain.
- Micro: Olfactory Neuroblastoma is characterized by fibrillary cytoplasm and interdigitating neuronal processes (neuropil), and Homer Wright rosettes are frequently observed.
- Ancillary: Immunohistochemistry in Olfactory Neuroblastoma typically shows diffuse staining for neuroendocrine markers and S100 reactivity in sustentacular cells.
Reference Gallery:
Olfactory neuroblastoma. Hyams grade I tumour showing a lobular architecture and a prominent fibrillary matrix. Homer Wright rosettes are noted.
Olfactory neuroblastoma. Hyams grade II tumour showing a lobular architecture. Moderate nuclear pleomorphism and occasional mitotic figures are noted.
Olfactory neuroblastoma. Hyams grade III tumour showing Flexner–Wintersteiner rosettes.
Olfactory neuroblastoma. Hyams grade IV tumour showing no fibrillary matrix. Mitotic figures are seen. Necrosis is seen.
Olfactory neuroblastoma, cytological touch preparation. The nuclei are round with delicate, salt-and-pepper chromatin and small nucleoli.
Olfactory neuroblastoma. T2-weighted axial MRI showing a large soft tissue lesion involving bilateral ethmoid air cells, destroying the intervening bony septum.
Olfactory neuroblastoma. Postcontrast fat-suppressed T1-weighted sagittal MRI demonstrates intracranial extension and a small, typical, tumoural cyst.
Olfactory neuroblastoma. Four years after treatment, the patient developed multiple metastatic cervical lymph nodes, the largest on the right side at level Ib (arrow).
Olfactory neuroblastoma. Gross appearance of a polypoid, red-grey mass.

Q: Cytological touch preparations of olfactory neuroblastoma characteristically demonstrate round nuclei with a delicate, [...] chromatin pattern.
Olfactory neuroblastoma, cytological touch preparation. The nuclei are round with delicate, salt-and-pepper chromatin and small nucleoli.
A: salt-and-pepper
Back Extra: Olfactory Neuroblastoma
- Clinical: Nasal obstruction is the most common symptom of Olfactory Neuroblastoma, often accompanied by epistaxis, nasal discharge, and/or pain.
- Micro: Olfactory Neuroblastoma is characterized by fibrillary cytoplasm and interdigitating neuronal processes (neuropil), and Homer Wright rosettes are frequently observed.
- Ancillary: Immunohistochemistry in Olfactory Neuroblastoma typically shows diffuse staining for neuroendocrine markers and S100 reactivity in sustentacular cells.
Reference Gallery:
Olfactory neuroblastoma. Hyams grade I tumour showing a lobular architecture and a prominent fibrillary matrix. Homer Wright rosettes are noted.
Olfactory neuroblastoma. Hyams grade II tumour showing a lobular architecture. Moderate nuclear pleomorphism and occasional mitotic figures are noted.
Olfactory neuroblastoma. Hyams grade III tumour showing Flexner–Wintersteiner rosettes.
Olfactory neuroblastoma. Hyams grade IV tumour showing no fibrillary matrix. Mitotic figures are seen. Necrosis is seen.
Olfactory neuroblastoma, cytological touch preparation. The nuclei are round with delicate, salt-and-pepper chromatin and small nucleoli.
Olfactory neuroblastoma. T2-weighted axial MRI showing a large soft tissue lesion involving bilateral ethmoid air cells, destroying the intervening bony septum.
Olfactory neuroblastoma. Postcontrast fat-suppressed T1-weighted sagittal MRI demonstrates intracranial extension and a small, typical, tumoural cyst.
Olfactory neuroblastoma. Four years after treatment, the patient developed multiple metastatic cervical lymph nodes, the largest on the right side at level Ib (arrow).
Olfactory neuroblastoma. Gross appearance of a polypoid, red-grey mass.

Q: Grossly, olfactory neuroblastoma typically presents as a red-gray, [...] mass that frequently causes nasal obstruction.
Olfactory neuroblastoma. Gross appearance of a polypoid, red-grey mass.
A: polypoid
Back Extra: Olfactory Neuroblastoma
- Clinical: Nasal obstruction is the most common symptom of Olfactory Neuroblastoma, often accompanied by epistaxis, nasal discharge, and/or pain.
- Micro: Olfactory Neuroblastoma is characterized by fibrillary cytoplasm and interdigitating neuronal processes (neuropil), and Homer Wright rosettes are frequently observed.
- Ancillary: Immunohistochemistry in Olfactory Neuroblastoma typically shows diffuse staining for neuroendocrine markers and S100 reactivity in sustentacular cells.
Reference Gallery:
Olfactory neuroblastoma. Hyams grade I tumour showing a lobular architecture and a prominent fibrillary matrix. Homer Wright rosettes are noted.
Olfactory neuroblastoma. Hyams grade II tumour showing a lobular architecture. Moderate nuclear pleomorphism and occasional mitotic figures are noted.
Olfactory neuroblastoma. Hyams grade III tumour showing Flexner–Wintersteiner rosettes.
Olfactory neuroblastoma. Hyams grade IV tumour showing no fibrillary matrix. Mitotic figures are seen. Necrosis is seen.
Olfactory neuroblastoma, cytological touch preparation. The nuclei are round with delicate, salt-and-pepper chromatin and small nucleoli.
Olfactory neuroblastoma. T2-weighted axial MRI showing a large soft tissue lesion involving bilateral ethmoid air cells, destroying the intervening bony septum.
Olfactory neuroblastoma. Postcontrast fat-suppressed T1-weighted sagittal MRI demonstrates intracranial extension and a small, typical, tumoural cyst.
Olfactory neuroblastoma. Four years after treatment, the patient developed multiple metastatic cervical lymph nodes, the largest on the right side at level Ib (arrow).
Olfactory neuroblastoma. Gross appearance of a polypoid, red-grey mass.

Q: In Adamantinomatous Craniopharyngioma, the epithelial nests characteristically display basal palisading, stellate reticulum, and nodules of [...] (also known as ghost cells).
Adamantinomatous craniopharyngioma. Basal palisading of tumour cells along the tumour–brain interface, epithelial whorls, stellate reticulum, and wet keratin (ghost cells).
A: wet keratin
Back Extra: Adamantinomatous Craniopharyngioma
- Clinical: Adamantinomatous craniopharyngioma within the sinonasal tract presents with nonspecific clinical findings, including headaches, visual changes, and endocrine deficits.
- Micro: The tumour consists of epithelium arranged in cords, lobules, ribbons, and nodular whorls, with basal palisading and wet keratin (ghost cells).
- Ancillary: Immunohistochemistry shows nuclear accumulation of β-catenin in a subset of cells, and CTNNB1 mutations are present.
Reference Gallery:
Adamantinomatous craniopharyngioma. Postcontrast T1-weighted MRI shows a suprasellar 37 mm predominantly cystic mass with a thin rim of enhancement extending into the third ventricle. There was a 16 mm region of nodular enhancement inferiorly. This male 18-year-old had a 2-month history of headache, which had become acutely worse with a new onset of nausea and vomiting. The mass demonstrated peripheral calcification on CT.
Adamantinomatous craniopharyngioma. Basal palisading of tumour cells along the tumour–brain interface, epithelial whorls, stellate reticulum, and wet keratin (ghost cells).
Adamantinomatous craniopharyngioma. High-power view of the interface of adamantinomatous craniopharyngioma and brain tissue; Rosenthal fibres are present in the reactive piloid gliosis.
Adamantinomatous craniopharyngioma. Even though mutations in exon 3 of CTNNB1, which encodes β-catenin, are clonal and present across the neoplastic epithelium, β-catenin protein only accumulates in the nucleus in a subset of cells, such as those present in epithelial whorls or surrounding wet keratin.

Q: Immunohistochemistry for Adamantinomatous Craniopharyngioma characteristically demonstrates nuclear accumulation of [...] in a subset of cells, which correlates with underlying CTNNB1 mutations.
Adamantinomatous craniopharyngioma. Even though mutations in exon 3 of CTNNB1, which encodes β-catenin, are clonal and present across the neoplastic epithelium, β-catenin protein only accumulates in the nucleus in a subset of cells, such as those present in epithelial whorls or surrounding wet keratin.
A: β-catenin
Back Extra: Adamantinomatous Craniopharyngioma
- Clinical: Adamantinomatous craniopharyngioma within the sinonasal tract presents with nonspecific clinical findings, including headaches, visual changes, and endocrine deficits.
- Micro: The tumour consists of epithelium arranged in cords, lobules, ribbons, and nodular whorls, with basal palisading and wet keratin (ghost cells).
- Ancillary: Immunohistochemistry shows nuclear accumulation of β-catenin in a subset of cells, and CTNNB1 mutations are present.
Reference Gallery:
Adamantinomatous craniopharyngioma. Postcontrast T1-weighted MRI shows a suprasellar 37 mm predominantly cystic mass with a thin rim of enhancement extending into the third ventricle. There was a 16 mm region of nodular enhancement inferiorly. This male 18-year-old had a 2-month history of headache, which had become acutely worse with a new onset of nausea and vomiting. The mass demonstrated peripheral calcification on CT.
Adamantinomatous craniopharyngioma. Basal palisading of tumour cells along the tumour–brain interface, epithelial whorls, stellate reticulum, and wet keratin (ghost cells).
Adamantinomatous craniopharyngioma. High-power view of the interface of adamantinomatous craniopharyngioma and brain tissue; Rosenthal fibres are present in the reactive piloid gliosis.
Adamantinomatous craniopharyngioma. Even though mutations in exon 3 of CTNNB1, which encodes β-catenin, are clonal and present across the neoplastic epithelium, β-catenin protein only accumulates in the nucleus in a subset of cells, such as those present in epithelial whorls or surrounding wet keratin.

Q: At the tumor-brain interface of an Adamantinomatous Craniopharyngioma, the surrounding brain tissue typically exhibits reactive piloid gliosis containing prominent [...].
Adamantinomatous craniopharyngioma. High-power view of the interface of adamantinomatous craniopharyngioma and brain tissue; Rosenthal fibres are present in the reactive piloid gliosis.
A: Rosenthal fibers
Back Extra: Adamantinomatous Craniopharyngioma
- Clinical: Adamantinomatous craniopharyngioma within the sinonasal tract presents with nonspecific clinical findings, including headaches, visual changes, and endocrine deficits.
- Micro: The tumour consists of epithelium arranged in cords, lobules, ribbons, and nodular whorls, with basal palisading and wet keratin (ghost cells).
- Ancillary: Immunohistochemistry shows nuclear accumulation of β-catenin in a subset of cells, and CTNNB1 mutations are present.
Reference Gallery:
Adamantinomatous craniopharyngioma. Postcontrast T1-weighted MRI shows a suprasellar 37 mm predominantly cystic mass with a thin rim of enhancement extending into the third ventricle. There was a 16 mm region of nodular enhancement inferiorly. This male 18-year-old had a 2-month history of headache, which had become acutely worse with a new onset of nausea and vomiting. The mass demonstrated peripheral calcification on CT.
Adamantinomatous craniopharyngioma. Basal palisading of tumour cells along the tumour–brain interface, epithelial whorls, stellate reticulum, and wet keratin (ghost cells).
Adamantinomatous craniopharyngioma. High-power view of the interface of adamantinomatous craniopharyngioma and brain tissue; Rosenthal fibres are present in the reactive piloid gliosis.
Adamantinomatous craniopharyngioma. Even though mutations in exon 3 of CTNNB1, which encodes β-catenin, are clonal and present across the neoplastic epithelium, β-catenin protein only accumulates in the nucleus in a subset of cells, such as those present in epithelial whorls or surrounding wet keratin.

Q: Microscopic examination of Meningioma of the sinonasal tract, ear, and temporal bone characteristically reveals a proliferation of meningothelial cells with a low to intermediate N:C ratio, psammoma bodies, and prominent [...].
Meningioma of the sinonasal tract. An intact respiratory epithelium is noted above a stromal proliferation of meningothelial cells. Note the small psammoma bodies and well-developed intranuclear cytoplasmic inclusions.
Meningioma. Meningioma of the sinonasal tract. Slight nuclear atypia may be seen in meningothelial meningioma. Intranuclear cytoplasmic inclusions are prominent in this field.
A: intranuclear cytoplasmic inclusions
Q: Meningioma of the sinonasal tract, ear, and temporal bone
- Clinical: Symptoms of [...] include nasal obstruction, epistaxis, and hearing loss, often presenting for years before diagnosis.
- Micro: Microscopic examination reveals meningothelial cells with a low to intermediate N:C ratio, intranuclear cytoplasmic inclusions, and psammoma bodies in [...].
- Ancillary: Immunohistochemical studies show [...] to be positive for EMA, SSTR2A, and MUC4.
Reference Gallery:
Meningioma of the sinonasal tract. A homogeneous mass is identified within the sphenoid sinus, associated with bone remodelling and hyperostosis, in this CT image.
Meningioma of the ear. Fragments of tissue show a meningothelial proliferation associated with innumerable variably sized psammoma bodies.
Meningioma of the ear. It is common to see meningioma within the interstices of bone. The tumour frequently grows through the bone from an intracranial primary to present either in the ear or in the sinonasal tract.
Meningioma of the sinonasal tract. The meningothelial pattern, composed of slightly spindled cells, is seen in this meningothelial meningioma.
Meningioma of the sinonasal tract. An intact respiratory epithelium is noted above a stromal proliferation of meningothelial cells. Note the small psammoma bodies and well-developed intranuclear cytoplasmic inclusions.
Meningioma of the sinonasal tract. The meningothelial proliferation is intimately associated with the surface squamous epithelium and the adjacent minor mucoserous glands. This finding sometimes mimics squamous cell carcinoma. However, the numerous intranuclear cytoplasmic inclusions help with interpretation.
Meningioma. Meningioma of the sinonasal tract. Slight nuclear atypia may be seen in meningothelial meningioma. Intranuclear cytoplasmic inclusions are prominent in this field.
Meningioma. Meningioma of the sinonasal tract. Fibrous meningiomas are the most difficult to recognize, because the neoplastic cells take on a spindled appearance within a background of collagen. Special studies are often required to confirm the diagnosis.
Meningioma. Meningioma of the ear. The psammomatous subtype of meningioma is seen more commonly in the ear than in the sinonasal tract. There are usually numerous psammoma bodies within the tumour.
Meningioma. Meningioma of the ear. The rhabdoid subtype of meningioma has eccentric eosinophilic cytoplasm in cells that show a syncytial architecture. This type of meningioma raises a different differential diagnosis than other subtypes, potentially requiring immunohistochemistry to resolve the diagnosis.
Meningioma of the ear. The neoplastic cells are highlighted by a membranous to cytoplasmic EMA reactivity.
A: Meningioma of the sinonasal tract, ear, and temporal bone; Meningioma of the sinonasal tract, ear, and temporal bone; Meningioma of the sinonasal tract, ear, and temporal bone

Q: Immunohistochemical evaluation of Meningioma of the sinonasal tract, ear, and temporal bone typically demonstrates characteristic membranous to cytoplasmic reactivity for [...] (in addition to SSTR2A positivity).
Meningioma of the ear. The neoplastic cells are highlighted by a membranous to cytoplasmic EMA reactivity.
A: EMA
Q: Meningioma of the sinonasal tract, ear, and temporal bone
- Clinical: Symptoms of [...] include nasal obstruction, epistaxis, and hearing loss, often presenting for years before diagnosis.
- Micro: Microscopic examination reveals meningothelial cells with a low to intermediate N:C ratio, intranuclear cytoplasmic inclusions, and psammoma bodies in [...].
- Ancillary: Immunohistochemical studies show [...] to be positive for EMA, SSTR2A, and MUC4.
Reference Gallery:
Meningioma of the sinonasal tract. A homogeneous mass is identified within the sphenoid sinus, associated with bone remodelling and hyperostosis, in this CT image.
Meningioma of the ear. Fragments of tissue show a meningothelial proliferation associated with innumerable variably sized psammoma bodies.
Meningioma of the ear. It is common to see meningioma within the interstices of bone. The tumour frequently grows through the bone from an intracranial primary to present either in the ear or in the sinonasal tract.
Meningioma of the sinonasal tract. The meningothelial pattern, composed of slightly spindled cells, is seen in this meningothelial meningioma.
Meningioma of the sinonasal tract. An intact respiratory epithelium is noted above a stromal proliferation of meningothelial cells. Note the small psammoma bodies and well-developed intranuclear cytoplasmic inclusions.
Meningioma of the sinonasal tract. The meningothelial proliferation is intimately associated with the surface squamous epithelium and the adjacent minor mucoserous glands. This finding sometimes mimics squamous cell carcinoma. However, the numerous intranuclear cytoplasmic inclusions help with interpretation.
Meningioma. Meningioma of the sinonasal tract. Slight nuclear atypia may be seen in meningothelial meningioma. Intranuclear cytoplasmic inclusions are prominent in this field.
Meningioma. Meningioma of the sinonasal tract. Fibrous meningiomas are the most difficult to recognize, because the neoplastic cells take on a spindled appearance within a background of collagen. Special studies are often required to confirm the diagnosis.
Meningioma. Meningioma of the ear. The psammomatous subtype of meningioma is seen more commonly in the ear than in the sinonasal tract. There are usually numerous psammoma bodies within the tumour.
Meningioma. Meningioma of the ear. The rhabdoid subtype of meningioma has eccentric eosinophilic cytoplasm in cells that show a syncytial architecture. This type of meningioma raises a different differential diagnosis than other subtypes, potentially requiring immunohistochemistry to resolve the diagnosis.
Meningioma of the ear. The neoplastic cells are highlighted by a membranous to cytoplasmic EMA reactivity.
A: Meningioma of the sinonasal tract, ear, and temporal bone; Meningioma of the sinonasal tract, ear, and temporal bone; Meningioma of the sinonasal tract, ear, and temporal bone

Q: On CT imaging, Meningioma of the sinonasal tract, ear, and temporal bone often presents as a homogeneous mass that is classically associated with bone remodeling and [...].
Meningioma of the sinonasal tract. A homogeneous mass is identified within the sphenoid sinus, associated with bone remodelling and hyperostosis, in this CT image.
A: hyperostosis
Q: Meningioma of the sinonasal tract, ear, and temporal bone
- Clinical: Symptoms of [...] include nasal obstruction, epistaxis, and hearing loss, often presenting for years before diagnosis.
- Micro: Microscopic examination reveals meningothelial cells with a low to intermediate N:C ratio, intranuclear cytoplasmic inclusions, and psammoma bodies in [...].
- Ancillary: Immunohistochemical studies show [...] to be positive for EMA, SSTR2A, and MUC4.
Reference Gallery:
Meningioma of the sinonasal tract. A homogeneous mass is identified within the sphenoid sinus, associated with bone remodelling and hyperostosis, in this CT image.
Meningioma of the ear. Fragments of tissue show a meningothelial proliferation associated with innumerable variably sized psammoma bodies.
Meningioma of the ear. It is common to see meningioma within the interstices of bone. The tumour frequently grows through the bone from an intracranial primary to present either in the ear or in the sinonasal tract.
Meningioma of the sinonasal tract. The meningothelial pattern, composed of slightly spindled cells, is seen in this meningothelial meningioma.
Meningioma of the sinonasal tract. An intact respiratory epithelium is noted above a stromal proliferation of meningothelial cells. Note the small psammoma bodies and well-developed intranuclear cytoplasmic inclusions.
Meningioma of the sinonasal tract. The meningothelial proliferation is intimately associated with the surface squamous epithelium and the adjacent minor mucoserous glands. This finding sometimes mimics squamous cell carcinoma. However, the numerous intranuclear cytoplasmic inclusions help with interpretation.
Meningioma. Meningioma of the sinonasal tract. Slight nuclear atypia may be seen in meningothelial meningioma. Intranuclear cytoplasmic inclusions are prominent in this field.
Meningioma. Meningioma of the sinonasal tract. Fibrous meningiomas are the most difficult to recognize, because the neoplastic cells take on a spindled appearance within a background of collagen. Special studies are often required to confirm the diagnosis.
Meningioma. Meningioma of the ear. The psammomatous subtype of meningioma is seen more commonly in the ear than in the sinonasal tract. There are usually numerous psammoma bodies within the tumour.
Meningioma. Meningioma of the ear. The rhabdoid subtype of meningioma has eccentric eosinophilic cytoplasm in cells that show a syncytial architecture. This type of meningioma raises a different differential diagnosis than other subtypes, potentially requiring immunohistochemistry to resolve the diagnosis.
Meningioma of the ear. The neoplastic cells are highlighted by a membranous to cytoplasmic EMA reactivity.
A: Meningioma of the sinonasal tract, ear, and temporal bone; Meningioma of the sinonasal tract, ear, and temporal bone; Meningioma of the sinonasal tract, ear, and temporal bone

Q: Histologically, Sinonasal Ameloblastoma is characterized by a basaloid epithelial neoplasm exhibiting a plexiform or follicular growth pattern, typically with a loosely arranged central [...]-like component.
Sinonasal ameloblastoma. Low-magnification view demonstrating plexiform patterned growth.
Sinonasal ameloblastoma. Tumour in direct continuity with intact sinonasal surface epithelium (far left).
A: stellate reticulum
Back Extra: Sinonasal Ameloblastoma
- Clinical: Sinonasal ameloblastoma commonly presents with nasal obstruction and/or epistaxis, and may extend into the nasal vestibule or cause orbitofacial deformity.
- Micro: The tumour is a basaloid epithelial neoplasm arranged in a plexiform or follicular pattern, with a loosely arranged stellate reticulum-like component centrally.
- Ancillary: Although not clinically relevant in sinonasal tract tumours, BRAF activating mutations are most common in jaw tumours, followed by mutually exclusive RAS mutations.
Reference Gallery:
Sinonasal ameloblastoma. Polypoid nasal vestibular projection of sinonasal ameloblastoma.
Sinonasal ameloblastoma. Tumour expands the maxillary sinus with extension into the nasal cavity (CT, axial plane).
Sinonasal ameloblastoma. Low-magnification view demonstrating plexiform patterned growth.
Sinonasal ameloblastoma. Tumour in direct continuity with intact sinonasal surface epithelium (far left).

Q: Clinically and radiologically, Sinonasal Ameloblastoma often expands the maxillary sinus and can present as a polypoid tumor extending into the [...].
Sinonasal ameloblastoma. Polypoid nasal vestibular projection of sinonasal ameloblastoma.
Sinonasal ameloblastoma. Tumour expands the maxillary sinus with extension into the nasal cavity (CT, axial plane).
A: nasal vestibule
Back Extra: Sinonasal Ameloblastoma
- Clinical: Sinonasal ameloblastoma commonly presents with nasal obstruction and/or epistaxis, and may extend into the nasal vestibule or cause orbitofacial deformity.
- Micro: The tumour is a basaloid epithelial neoplasm arranged in a plexiform or follicular pattern, with a loosely arranged stellate reticulum-like component centrally.
- Ancillary: Although not clinically relevant in sinonasal tract tumours, BRAF activating mutations are most common in jaw tumours, followed by mutually exclusive RAS mutations.
Reference Gallery:
Sinonasal ameloblastoma. Polypoid nasal vestibular projection of sinonasal ameloblastoma.
Sinonasal ameloblastoma. Tumour expands the maxillary sinus with extension into the nasal cavity (CT, axial plane).
Sinonasal ameloblastoma. Low-magnification view demonstrating plexiform patterned growth.
Sinonasal ameloblastoma. Tumour in direct continuity with intact sinonasal surface epithelium (far left).

Q: Histologically, Sinonasal Papilloma, Exophytic is characterized by finger-like papillary fronds with fibrovascular cores that are covered by a maturing, multilayered squamous epithelium often containing superficial [...].
Sinonasal papilloma, exophytic. The lesion is exophytic and covered by a maturing multilayered squamous epithelium.
Sinonasal papilloma, exophytic. Maturing squamous epithelium with superficial koilocytes lines these finger-like projections. Scattered transmigrating intraepithelial neutrophils are seen.
A: koilocytes
Back Extra: Sinonasal Papilloma, Exophytic
- Clinical: Typical presenting symptoms include epistaxis and unilateral nasal obstruction caused by a mass lesion.
- Micro: Exophytic sinonasal papillomas are composed of papillary fronds with fibrovascular cores covered by a proliferative, multilayered epithelium that is 5–20 cells thick.
- Ancillary: The majority of these tumours harbour low-risk HPV (mostly types 6 and 11).
Reference Gallery:
Sinonasal papilloma, exophytic. Most exophytic sinonasal papillomas harbour low-risk HPV, demonstrated here by RNA in situ hybridization for HPV types 6 and 11.
Sinonasal papilloma, exophytic. The lesion is exophytic and covered by a maturing multilayered squamous epithelium.
Sinonasal papilloma, exophytic. Maturing squamous epithelium with superficial koilocytes lines these finger-like projections. Scattered transmigrating intraepithelial neutrophils are seen.

Q: The majority of Sinonasal Papilloma, Exophytic tumors harbor low-risk [...], which can be confirmed using RNA in situ hybridization.
Sinonasal papilloma, exophytic. Most exophytic sinonasal papillomas harbour low-risk HPV, demonstrated here by RNA in situ hybridization for HPV types 6 and 11.
A: human papillomavirus (HPV) types 6 and 11
Back Extra: Sinonasal Papilloma, Exophytic
- Clinical: Typical presenting symptoms include epistaxis and unilateral nasal obstruction caused by a mass lesion.
- Micro: Exophytic sinonasal papillomas are composed of papillary fronds with fibrovascular cores covered by a proliferative, multilayered epithelium that is 5–20 cells thick.
- Ancillary: The majority of these tumours harbour low-risk HPV (mostly types 6 and 11).
Reference Gallery:
Sinonasal papilloma, exophytic. Most exophytic sinonasal papillomas harbour low-risk HPV, demonstrated here by RNA in situ hybridization for HPV types 6 and 11.
Sinonasal papilloma, exophytic. The lesion is exophytic and covered by a maturing multilayered squamous epithelium.
Sinonasal papilloma, exophytic. Maturing squamous epithelium with superficial koilocytes lines these finger-like projections. Scattered transmigrating intraepithelial neutrophils are seen.

Q: The characteristic microscopic findings of Sinonasal Papilloma, Oncocytic include multilayered oncocytic epithelium containing intraepithelial microcysts and [...].
Sinonasal papilloma, oncocytic. High-power view showing the characteristic oncocytic cuboidal to columnar cells and intraepithelial microcysts with mucin and/or neutrophilic microabscesses.
A: neutrophilic microabscesses
Back Extra: Sinonasal Papilloma, Oncocytic
- Clinical: Patients with Sinonasal Papilloma, Oncocytic (OSP) typically present with unilateral nasal obstruction, rhinorrhoea, epistaxis, and/or anosmia.
- Micro: OSP is characterized by multilayered oncocytic cuboidal to columnar epithelium with intraepithelial microcysts and neutrophilic microabscesses.
- Ancillary: KRAS mutations in exons 2 or 3 are common in OSP, leading to constitutive KRAS activity and downstream pathway activation.
Reference Gallery:
Sinonasal papilloma, oncocytic. Low-power view highlighting the mixed exophytic and endophytic growth pattern.
Sinonasal papilloma, oncocytic. High-power view showing the characteristic oncocytic cuboidal to columnar cells and intraepithelial microcysts with mucin and/or neutrophilic microabscesses.
Sinonasal papilloma, oncocytic, with dysplasia. There is increased nuclear atypia and mitotic activity (right half of image) characteristic of dysplasia.
Sinonasal papilloma, oncocytic, with associated sinonasal carcinoma. Infiltrating nests of atypical squamous epithelial cells involve bone, corresponding to a sinonasal carcinoma arising in association with sinonasal papilloma, oncocytic.

Q: Molecularly, Sinonasal Papilloma, Oncocytic is commonly associated with activating mutations in the [...] gene (exons 2 or 3).
Sinonasal papilloma, oncocytic. High-power view showing the characteristic oncocytic cuboidal to columnar cells and intraepithelial microcysts with mucin and/or neutrophilic microabscesses.
A: KRAS
Back Extra: Sinonasal Papilloma, Oncocytic
- Clinical: Patients with Sinonasal Papilloma, Oncocytic (OSP) typically present with unilateral nasal obstruction, rhinorrhoea, epistaxis, and/or anosmia.
- Micro: OSP is characterized by multilayered oncocytic cuboidal to columnar epithelium with intraepithelial microcysts and neutrophilic microabscesses.
- Ancillary: KRAS mutations in exons 2 or 3 are common in OSP, leading to constitutive KRAS activity and downstream pathway activation.
Reference Gallery:
Sinonasal papilloma, oncocytic. Low-power view highlighting the mixed exophytic and endophytic growth pattern.
Sinonasal papilloma, oncocytic. High-power view showing the characteristic oncocytic cuboidal to columnar cells and intraepithelial microcysts with mucin and/or neutrophilic microabscesses.
Sinonasal papilloma, oncocytic, with dysplasia. There is increased nuclear atypia and mitotic activity (right half of image) characteristic of dysplasia.
Sinonasal papilloma, oncocytic, with associated sinonasal carcinoma. Infiltrating nests of atypical squamous epithelial cells involve bone, corresponding to a sinonasal carcinoma arising in association with sinonasal papilloma, oncocytic.

Q: Microscopically, a spindle cell Lipoma is characteristically composed of an admixture of mature adipocytes, bland spindle cells, and thick bundles of [...].
Spindle cell lipoma. There are adipocytes blended with thick collagen bundles, with areas of myxoid change. Nuclear pleomorphism is not identified.
Spindle cell lipoma. At low magnification, a typical mixture of adipocytes, spindle cells, and thick collagen bundles can be seen.
A: collagen
Back Extra: Lipoma
- Clinical: Lipomas are more common in men than women and typically present as slowly growing, asymptomatic, circumscribed masses <5 mm in diameter.
- Micro: Spindle cell lipoma is characterized by a mixture of adipocytes, bland spindle cells, and thick collagen bundles, often with areas of myxoid change.
- Ancillary: Loss of RB1 can be detected in the neoplastic cells of spindle cell and pleomorphic lipomas, which helps in their diagnosis.
Reference Gallery:
Spindle cell lipoma. At low magnification, there is a well-circumscribed tumour, showing an increased cellularity with collagen bands.
Spindle cell lipoma. There are adipocytes blended with thick collagen bundles, with areas of myxoid change. Nuclear pleomorphism is not identified.
Spindle cell lipoma. It is common to see myxoid change in spindle cell lipoma, as is noted in this example; there is dissection between collagen bundles of the myxoid material.
Spindle cell lipoma. This field shows only bland spindled cells set within a collagenous stroma.
Pleomorphic lipoma. There is anisonucleosis along with lipoblast-like cells in this pleomorphic lipoma. Note the numerous mast cells in the background.
Spindle cell lipoma. At low magnification, a typical mixture of adipocytes, spindle cells, and thick collagen bundles can be seen.
Spindle cell lipoma. There are scattered small multinucleated cells.
Spindle cell lipoma. A low-fat cellular spindle cell lipoma closely mimicking solitary fibrous tumour.
Spindle cell lipoma. Low-fat cellular spindle cell lipoma closely mimicking solitary fibrous tumour.
Spindle cell lipoma. Diffuse CD34 expression.
Spindle cell lipoma. Loss of RB1 in the neoplastic cells of spindle cell lipoma, but not in the stromal fibroblasts and endothelium.
Dysplastic lipoma. Distorted lipogenesis is accompanied by prominent CD68-positive macrophages encasing single fat cells in a ring-like manner.

Q: In spindle cell and pleomorphic variants of Lipoma, the neoplastic cells classically demonstrate loss of the tumor suppressor [...] by immunohistochemistry.
Spindle cell lipoma. Loss of RB1 in the neoplastic cells of spindle cell lipoma, but not in the stromal fibroblasts and endothelium.
A: RB1
Back Extra: Lipoma
- Clinical: Lipomas are more common in men than women and typically present as slowly growing, asymptomatic, circumscribed masses <5 mm in diameter.
- Micro: Spindle cell lipoma is characterized by a mixture of adipocytes, bland spindle cells, and thick collagen bundles, often with areas of myxoid change.
- Ancillary: Loss of RB1 can be detected in the neoplastic cells of spindle cell and pleomorphic lipomas, which helps in their diagnosis.
Reference Gallery:
Spindle cell lipoma. At low magnification, there is a well-circumscribed tumour, showing an increased cellularity with collagen bands.
Spindle cell lipoma. There are adipocytes blended with thick collagen bundles, with areas of myxoid change. Nuclear pleomorphism is not identified.
Spindle cell lipoma. It is common to see myxoid change in spindle cell lipoma, as is noted in this example; there is dissection between collagen bundles of the myxoid material.
Spindle cell lipoma. This field shows only bland spindled cells set within a collagenous stroma.
Pleomorphic lipoma. There is anisonucleosis along with lipoblast-like cells in this pleomorphic lipoma. Note the numerous mast cells in the background.
Spindle cell lipoma. At low magnification, a typical mixture of adipocytes, spindle cells, and thick collagen bundles can be seen.
Spindle cell lipoma. There are scattered small multinucleated cells.
Spindle cell lipoma. A low-fat cellular spindle cell lipoma closely mimicking solitary fibrous tumour.
Spindle cell lipoma. Low-fat cellular spindle cell lipoma closely mimicking solitary fibrous tumour.
Spindle cell lipoma. Diffuse CD34 expression.
Spindle cell lipoma. Loss of RB1 in the neoplastic cells of spindle cell lipoma, but not in the stromal fibroblasts and endothelium.
Dysplastic lipoma. Distorted lipogenesis is accompanied by prominent CD68-positive macrophages encasing single fat cells in a ring-like manner.

Q: Immunohistochemically, the bland spindle cells in a spindle cell Lipoma characteristically demonstrate diffuse expression of [...].
Spindle cell lipoma. Diffuse CD34 expression.
A: CD34
Back Extra: Lipoma
- Clinical: Lipomas are more common in men than women and typically present as slowly growing, asymptomatic, circumscribed masses <5 mm in diameter.
- Micro: Spindle cell lipoma is characterized by a mixture of adipocytes, bland spindle cells, and thick collagen bundles, often with areas of myxoid change.
- Ancillary: Loss of RB1 can be detected in the neoplastic cells of spindle cell and pleomorphic lipomas, which helps in their diagnosis.
Reference Gallery:
Spindle cell lipoma. At low magnification, there is a well-circumscribed tumour, showing an increased cellularity with collagen bands.
Spindle cell lipoma. There are adipocytes blended with thick collagen bundles, with areas of myxoid change. Nuclear pleomorphism is not identified.
Spindle cell lipoma. It is common to see myxoid change in spindle cell lipoma, as is noted in this example; there is dissection between collagen bundles of the myxoid material.
Spindle cell lipoma. This field shows only bland spindled cells set within a collagenous stroma.
Pleomorphic lipoma. There is anisonucleosis along with lipoblast-like cells in this pleomorphic lipoma. Note the numerous mast cells in the background.
Spindle cell lipoma. At low magnification, a typical mixture of adipocytes, spindle cells, and thick collagen bundles can be seen.
Spindle cell lipoma. There are scattered small multinucleated cells.
Spindle cell lipoma. A low-fat cellular spindle cell lipoma closely mimicking solitary fibrous tumour.
Spindle cell lipoma. Low-fat cellular spindle cell lipoma closely mimicking solitary fibrous tumour.
Spindle cell lipoma. Diffuse CD34 expression.
Spindle cell lipoma. Loss of RB1 in the neoplastic cells of spindle cell lipoma, but not in the stromal fibroblasts and endothelium.
Dysplastic lipoma. Distorted lipogenesis is accompanied by prominent CD68-positive macrophages encasing single fat cells in a ring-like manner.

Q: In myxoid Liposarcoma, the histology is characterized by prelipoblasts and lipoblasts set in a myxoid matrix, often with a characteristic [...].
Myxoid liposarcoma. This type of liposarcoma is composed of prelipoblasts and (univacuolar) lipoblasts set in a myxoid matrix. Note the typical peripheral condensation of cells in the lower part of the field.
A: plexiform capillary network
Back Extra: Liposarcoma
- Clinical: Liposarcomas account for 2–9% of sarcomas in the head and neck, with a mean patient age of 60 years.
- Micro: Myxoid liposarcoma is characterized by prelipoblasts and lipoblasts set in a myxoid matrix, often with a characteristic plexiform capillary network.
- Ancillary: Well-differentiated liposarcoma and dedifferentiated liposarcoma are positive for MDM2 and CDK4 on immunohistochemistry.
Reference Gallery:
Dedifferentiated liposarcoma. This field shows the abrupt transition from well-differentiated liposarcoma to a non-lipogenic sarcoma.
Myxoid liposarcoma. This type of liposarcoma is composed of prelipoblasts and (univacuolar) lipoblasts set in a myxoid matrix. Note the typical peripheral condensation of cells in the lower part of the field.
Pleomorphic myxoid liposarcoma. This field shows atypical univacuolated and plurivacuolated lipoblasts and pleomorphic cells in a prominent myxoid matrix.

Q: Histologically, dedifferentiated Liposarcoma characteristically demonstrates an abrupt transition from a well-differentiated liposarcoma to a [...].
Dedifferentiated liposarcoma. This field shows the abrupt transition from well-differentiated liposarcoma to a non-lipogenic sarcoma.
A: non-lipogenic sarcoma
Back Extra: Liposarcoma
- Clinical: Liposarcomas account for 2–9% of sarcomas in the head and neck, with a mean patient age of 60 years.
- Micro: Myxoid liposarcoma is characterized by prelipoblasts and lipoblasts set in a myxoid matrix, often with a characteristic plexiform capillary network.
- Ancillary: Well-differentiated liposarcoma and dedifferentiated liposarcoma are positive for MDM2 and CDK4 on immunohistochemistry.
Reference Gallery:
Dedifferentiated liposarcoma. This field shows the abrupt transition from well-differentiated liposarcoma to a non-lipogenic sarcoma.
Myxoid liposarcoma. This type of liposarcoma is composed of prelipoblasts and (univacuolar) lipoblasts set in a myxoid matrix. Note the typical peripheral condensation of cells in the lower part of the field.
Pleomorphic myxoid liposarcoma. This field shows atypical univacuolated and plurivacuolated lipoblasts and pleomorphic cells in a prominent myxoid matrix.

Q: A benign, slowly growing mass composed of nodules of mature hyaline cartilage separated by fibrous septa, notably lacking mitotic figures and binucleated forms, is diagnostic of a(n) [...].
Chondroma arising in the maxillary alveolus. Nodules of hyaline cartilage are present, separated by fibrous septa. Chondrocytes contain small hyperchromatic nuclei.
Chondroma arising in the maxillary alveolus. Higher-power view of chondrocytes with hyperchromatic nuclei showing no binucleated forms and no mitotic figures.
A: Chondroma
Back Extra: Chondroma
- Clinical: Chondromas are painless, firm, and slowly growing masses, often found in middle-aged patients with a male predominance (M:F ratio: 1.5:1).
- Micro: Chondromas are nodular tumors composed of mature hyaline or myxoid cartilage, with lobules separated by fibrous septa. Chondrocytes may show hyperchromatic nuclei, but no binucleated forms or mitotic figures.
- Ancillary: Cytogenetic analyses reveal rearrangements of 12q13-q15 and trisomy 5. FN1 gene rearrangements are present in about 50% of cases, with FGFR1 and FGFR2 as fusion partners.
Reference Gallery:
Chondroma arising in the maxillary alveolus. Biopsies are often fragmented as seen here. Islands of hyaline cartilage may be present in the mucosa beneath intact epithelium.
Chondroma arising in the maxillary alveolus. Nodules of hyaline cartilage are present, separated by fibrous septa. Chondrocytes contain small hyperchromatic nuclei.
Chondroma arising in the maxillary alveolus. Higher-power view of chondrocytes with hyperchromatic nuclei showing no binucleated forms and no mitotic figures.
Chondroma in nasal septum. At some sites, such as the larynx and nasal septum, chondroma may erode into adjacent bone, mimicking malignancy.
Chondroma of the tongue. A nodule of fibrohyaline cartilage is present in the stroma beneath intact epithelium.

Q: Although histologically benign, a Chondroma arising in specific sites like the nasal septum or larynx may clinically mimic a malignancy by [...].
Chondroma in nasal septum. At some sites, such as the larynx and nasal septum, chondroma may erode into adjacent bone, mimicking malignancy.
A: eroding into adjacent bone
Back Extra: Chondroma
- Clinical: Chondromas are painless, firm, and slowly growing masses, often found in middle-aged patients with a male predominance (M:F ratio: 1.5:1).
- Micro: Chondromas are nodular tumors composed of mature hyaline or myxoid cartilage, with lobules separated by fibrous septa. Chondrocytes may show hyperchromatic nuclei, but no binucleated forms or mitotic figures.
- Ancillary: Cytogenetic analyses reveal rearrangements of 12q13-q15 and trisomy 5. FN1 gene rearrangements are present in about 50% of cases, with FGFR1 and FGFR2 as fusion partners.
Reference Gallery:
Chondroma arising in the maxillary alveolus. Biopsies are often fragmented as seen here. Islands of hyaline cartilage may be present in the mucosa beneath intact epithelium.
Chondroma arising in the maxillary alveolus. Nodules of hyaline cartilage are present, separated by fibrous septa. Chondrocytes contain small hyperchromatic nuclei.
Chondroma arising in the maxillary alveolus. Higher-power view of chondrocytes with hyperchromatic nuclei showing no binucleated forms and no mitotic figures.
Chondroma in nasal septum. At some sites, such as the larynx and nasal septum, chondroma may erode into adjacent bone, mimicking malignancy.
Chondroma of the tongue. A nodule of fibrohyaline cartilage is present in the stroma beneath intact epithelium.

Q: Histologically, [...] is composed of long fascicles of uniform myofibroblasts with slender, tapering nuclei set in a collagenous or myxoid background.
Desmoid fibromatosis. There are long fascicles of uniform myofibroblasts in bundles with tapered nuclei. Lymphocytes are sometimes obvious at the margin.
A: desmoid fibromatosis
Back Extra: Desmoid Fibromatosis
- Clinical: Desmoid fibromatosis is typically asymptomatic but can become symptomatic by forming a mass and invading adjacent structures like bone, nerves, and vasculature.
- Micro: Histologically, the tumor is composed of long fascicles of uniform myofibroblasts with slender, tapering nuclei and inconspicuous cytoplasm, set in a collagenous or myxoid background.
- Ancillary: Somatic mutations in exon 3 of CTNNB1, leading to nuclear β-catenin expression, are a common finding and can help in diagnosis.
Reference Gallery:
Desmoid fibromatosis. There are long fascicles of uniform myofibroblasts in bundles with tapered nuclei. Lymphocytes are sometimes obvious at the margin.
Desmoid fibromatosis. Tumours may show desmin and/or SMA expression in the myofibroblasts.
Desmoid fibromatosis. Nuclear expression of β-catenin is characteristic.

Q: Immunohistochemical expression of SMA and/or desmin within long fascicles of uniform myofibroblasts is an expected ancillary finding in [...].
Desmoid fibromatosis. Tumours may show desmin and/or SMA expression in the myofibroblasts.
A: desmoid fibromatosis
Back Extra: Desmoid Fibromatosis
- Clinical: Desmoid fibromatosis is typically asymptomatic but can become symptomatic by forming a mass and invading adjacent structures like bone, nerves, and vasculature.
- Micro: Histologically, the tumor is composed of long fascicles of uniform myofibroblasts with slender, tapering nuclei and inconspicuous cytoplasm, set in a collagenous or myxoid background.
- Ancillary: Somatic mutations in exon 3 of CTNNB1, leading to nuclear β-catenin expression, are a common finding and can help in diagnosis.
Reference Gallery:
Desmoid fibromatosis. There are long fascicles of uniform myofibroblasts in bundles with tapered nuclei. Lymphocytes are sometimes obvious at the margin.
Desmoid fibromatosis. Tumours may show desmin and/or SMA expression in the myofibroblasts.
Desmoid fibromatosis. Nuclear expression of β-catenin is characteristic.

Q: A highly characteristic ancillary finding in desmoid fibromatosis is the aberrant nuclear expression of [...], reflecting underlying somatic mutations in CTNNB1.
Desmoid fibromatosis. Nuclear expression of β-catenin is characteristic.
A: β-catenin
Back Extra: Desmoid Fibromatosis
- Clinical: Desmoid fibromatosis is typically asymptomatic but can become symptomatic by forming a mass and invading adjacent structures like bone, nerves, and vasculature.
- Micro: Histologically, the tumor is composed of long fascicles of uniform myofibroblasts with slender, tapering nuclei and inconspicuous cytoplasm, set in a collagenous or myxoid background.
- Ancillary: Somatic mutations in exon 3 of CTNNB1, leading to nuclear β-catenin expression, are a common finding and can help in diagnosis.
Reference Gallery:
Desmoid fibromatosis. There are long fascicles of uniform myofibroblasts in bundles with tapered nuclei. Lymphocytes are sometimes obvious at the margin.
Desmoid fibromatosis. Tumours may show desmin and/or SMA expression in the myofibroblasts.
Desmoid fibromatosis. Nuclear expression of β-catenin is characteristic.

Q: Histologically, [...] is characterized by a proliferation of myofibroblasts that can exhibit myxoid, hypercellular, and hypocellular patterns, typically accompanied by a chronic inflammatory infiltrate.
Laryngeal inflammatory myofibroblastic tumour. In the myxoid pattern, plump myofibroblasts are set in an oedematous background with blood vessels and a chronic inflammatory infiltrate rich in lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour of the tongue. Lesional cells are arranged in fascicles in the hypercellular pattern. This example shows limited chronic inflammation, and the tumour cells infiltrate skeletal muscle. This tumour harboured a CARS1 (CARS)::ALK fusion gene.
Laryngeal inflammatory myofibroblastic tumour. Collagenous stroma predominates in the hypocellular pattern, with a relatively limited proliferation of elongated spindle cells and associated chronic inflammatory cells.
A: Inflammatory Myofibroblastic Tumor
Back Extra: Inflammatory Myofibroblastic Tumour
- Clinical: Patients with laryngeal inflammatory myofibroblastic tumours typically present with hoarseness and dysphonia, while those with sinonasal and skull base tumours experience nasal obstruction, pain, visual changes, and cranial nerve palsies.
- Micro: Inflammatory myofibroblastic tumours can show three principal patterns: myxoid, hypercellular, and hypocellular. The myofibroblasts have eosinophilic cytoplasm and vesicular nuclei with small nucleoli, often with a chronic inflammatory infiltrate.
- Ancillary: Immunohistochemistry (IHC) commonly shows ALK expression, especially in patients under 40 years of age. Molecular studies often reveal ALK gene rearrangements, with TIMP3 being a common fusion partner in head and neck IMTs.
Reference Gallery:
Laryngeal inflammatory myofibroblastic tumour. In the myxoid pattern, plump myofibroblasts are set in an oedematous background with blood vessels and a chronic inflammatory infiltrate rich in lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour of the tongue. Lesional cells are arranged in fascicles in the hypercellular pattern. This example shows limited chronic inflammation, and the tumour cells infiltrate skeletal muscle. This tumour harboured a CARS1 (CARS)::ALK fusion gene.
Laryngeal inflammatory myofibroblastic tumour. Collagenous stroma predominates in the hypocellular pattern, with a relatively limited proliferation of elongated spindle cells and associated chronic inflammatory cells.
Inflammatory myofibroblastic tumour of the oral mucosa. The spindle-shaped myofibroblasts have oval nuclei and vesicular chromatin with small, prominent nucleoli; scattered intranuclear pseudoinclusions can be seen.
Hypopharyngeal inflammatory myofibroblastic tumour after crizotinib therapy. A large inflammatory myofibroblastic tumour of the hypopharynx is grossly lobulated, tan, and fleshy, with areas of necrosis (yellow, left), after neoadjuvant treatment with crizotinib. This tumour harboured a ROS1 gene rearrangement, an unusual feature for head and neck inflammatory myofibroblastic tumours.
Laryngeal inflammatory myofibroblastic tumour. The submucosal myofibroblastic spindle cell proliferation is diffusely and strongly positive for ALK by immunohistochemistry. This tumour harboured a TIMP3::ALK rearrangement.

Q: In Inflammatory Myofibroblastic Tumor, immunohistochemistry commonly shows diffuse and strong expression of [...], which correlates with underlying gene rearrangements often seen in patients under 40 years of age.
Laryngeal inflammatory myofibroblastic tumour. The submucosal myofibroblastic spindle cell proliferation is diffusely and strongly positive for ALK by immunohistochemistry. This tumour harboured a TIMP3::ALK rearrangement.
A: ALK
Back Extra: Inflammatory Myofibroblastic Tumour
- Clinical: Patients with laryngeal inflammatory myofibroblastic tumours typically present with hoarseness and dysphonia, while those with sinonasal and skull base tumours experience nasal obstruction, pain, visual changes, and cranial nerve palsies.
- Micro: Inflammatory myofibroblastic tumours can show three principal patterns: myxoid, hypercellular, and hypocellular. The myofibroblasts have eosinophilic cytoplasm and vesicular nuclei with small nucleoli, often with a chronic inflammatory infiltrate.
- Ancillary: Immunohistochemistry (IHC) commonly shows ALK expression, especially in patients under 40 years of age. Molecular studies often reveal ALK gene rearrangements, with TIMP3 being a common fusion partner in head and neck IMTs.
Reference Gallery:
Laryngeal inflammatory myofibroblastic tumour. In the myxoid pattern, plump myofibroblasts are set in an oedematous background with blood vessels and a chronic inflammatory infiltrate rich in lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour of the tongue. Lesional cells are arranged in fascicles in the hypercellular pattern. This example shows limited chronic inflammation, and the tumour cells infiltrate skeletal muscle. This tumour harboured a CARS1 (CARS)::ALK fusion gene.
Laryngeal inflammatory myofibroblastic tumour. Collagenous stroma predominates in the hypocellular pattern, with a relatively limited proliferation of elongated spindle cells and associated chronic inflammatory cells.
Inflammatory myofibroblastic tumour of the oral mucosa. The spindle-shaped myofibroblasts have oval nuclei and vesicular chromatin with small, prominent nucleoli; scattered intranuclear pseudoinclusions can be seen.
Hypopharyngeal inflammatory myofibroblastic tumour after crizotinib therapy. A large inflammatory myofibroblastic tumour of the hypopharynx is grossly lobulated, tan, and fleshy, with areas of necrosis (yellow, left), after neoadjuvant treatment with crizotinib. This tumour harboured a ROS1 gene rearrangement, an unusual feature for head and neck inflammatory myofibroblastic tumours.
Laryngeal inflammatory myofibroblastic tumour. The submucosal myofibroblastic spindle cell proliferation is diffusely and strongly positive for ALK by immunohistochemistry. This tumour harboured a TIMP3::ALK rearrangement.

Q: Molecular studies of head and neck Inflammatory Myofibroblastic Tumor often reveal ALK gene rearrangements, with [...] being a common fusion partner.
Laryngeal inflammatory myofibroblastic tumour. The submucosal myofibroblastic spindle cell proliferation is diffusely and strongly positive for ALK by immunohistochemistry. This tumour harboured a TIMP3::ALK rearrangement.
A: TIMP3
Back Extra: Inflammatory Myofibroblastic Tumour
- Clinical: Patients with laryngeal inflammatory myofibroblastic tumours typically present with hoarseness and dysphonia, while those with sinonasal and skull base tumours experience nasal obstruction, pain, visual changes, and cranial nerve palsies.
- Micro: Inflammatory myofibroblastic tumours can show three principal patterns: myxoid, hypercellular, and hypocellular. The myofibroblasts have eosinophilic cytoplasm and vesicular nuclei with small nucleoli, often with a chronic inflammatory infiltrate.
- Ancillary: Immunohistochemistry (IHC) commonly shows ALK expression, especially in patients under 40 years of age. Molecular studies often reveal ALK gene rearrangements, with TIMP3 being a common fusion partner in head and neck IMTs.
Reference Gallery:
Laryngeal inflammatory myofibroblastic tumour. In the myxoid pattern, plump myofibroblasts are set in an oedematous background with blood vessels and a chronic inflammatory infiltrate rich in lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour of the tongue. Lesional cells are arranged in fascicles in the hypercellular pattern. This example shows limited chronic inflammation, and the tumour cells infiltrate skeletal muscle. This tumour harboured a CARS1 (CARS)::ALK fusion gene.
Laryngeal inflammatory myofibroblastic tumour. Collagenous stroma predominates in the hypocellular pattern, with a relatively limited proliferation of elongated spindle cells and associated chronic inflammatory cells.
Inflammatory myofibroblastic tumour of the oral mucosa. The spindle-shaped myofibroblasts have oval nuclei and vesicular chromatin with small, prominent nucleoli; scattered intranuclear pseudoinclusions can be seen.
Hypopharyngeal inflammatory myofibroblastic tumour after crizotinib therapy. A large inflammatory myofibroblastic tumour of the hypopharynx is grossly lobulated, tan, and fleshy, with areas of necrosis (yellow, left), after neoadjuvant treatment with crizotinib. This tumour harboured a ROS1 gene rearrangement, an unusual feature for head and neck inflammatory myofibroblastic tumours.
Laryngeal inflammatory myofibroblastic tumour. The submucosal myofibroblastic spindle cell proliferation is diffusely and strongly positive for ALK by immunohistochemistry. This tumour harboured a TIMP3::ALK rearrangement.

Q: A characteristic histologic finding in Low-grade myofibroblastic sarcoma is the [...]-like infiltration of adjacent skeletal muscle.
Myofibroblastic sarcoma. Infiltration of the skeletal muscle.
Myofibroblastic sarcoma. Infiltration into the voluntary muscle leads to a typical checkerboard pattern.
A: checkerboard
Back Extra: Low-grade myofibroblastic sarcoma
- Clinical: Low-grade myofibroblastic sarcoma typically presents as a slowly growing, painless mass in the head and neck region, most commonly in the tongue, larynx, and gingiva.
- Micro: Key microscopic features include checkerboard-like infiltration of adjacent skeletal muscle and fascicles of myofibroblastic cells with enlarged, tapered, hyperchromatic nuclei.
- Ancillary: Immunohistochemistry shows variable expression of SMA, desmin, calponin, and CD34, with focal expression of H-caldesmon in some cases.
Reference Gallery:
Myofibroblastic sarcoma. Infiltration of the skeletal muscle.
Myofibroblastic sarcoma. Infiltration into the voluntary muscle leads to a typical checkerboard pattern.
Myofibroblastic sarcoma. The myofibroblastic cells are arranged in long fascicles bearing a resemblance to desmoid fibromatosis.

Q: Microscopically, [...] features spindle cells arranged in long fascicles that bear a strong histologic resemblance to desmoid fibromatosis.
Myofibroblastic sarcoma. The myofibroblastic cells are arranged in long fascicles bearing a resemblance to desmoid fibromatosis.
A: Low-grade myofibroblastic sarcoma
Back Extra: Low-grade myofibroblastic sarcoma
- Clinical: Low-grade myofibroblastic sarcoma typically presents as a slowly growing, painless mass in the head and neck region, most commonly in the tongue, larynx, and gingiva.
- Micro: Key microscopic features include checkerboard-like infiltration of adjacent skeletal muscle and fascicles of myofibroblastic cells with enlarged, tapered, hyperchromatic nuclei.
- Ancillary: Immunohistochemistry shows variable expression of SMA, desmin, calponin, and CD34, with focal expression of H-caldesmon in some cases.
Reference Gallery:
Myofibroblastic sarcoma. Infiltration of the skeletal muscle.
Myofibroblastic sarcoma. Infiltration into the voluntary muscle leads to a typical checkerboard pattern.
Myofibroblastic sarcoma. The myofibroblastic cells are arranged in long fascicles bearing a resemblance to desmoid fibromatosis.

Q: Histologically, Nodular Fasciitis classically features plump, spindle-shaped myofibroblasts arranged in a loosely cohesive, [...] architecture within a fibromyxoid stroma.
Nodular fasciitis. This field shows the tissue culture–like appearance of nodular fasciitis.
Nodular fasciitis. Bland-looking myofibroblastic cells are loosely arranged in a fibromyxoid matrix.
A: tissue culture-like
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis grows rapidly and usually has a preoperative duration of ≤ 2–3 months; it often measures ≤ 30 mm on excision.
- Micro: The lesion is composed of plump, spindle-shaped cells with a tissue culture–like architecture and a variably myxoid stroma.
- Ancillary: USP6 rearrangement is a characteristic feature and can confirm the diagnosis.
Reference Gallery:
Nodular fasciitis. The lesion is often circumscribed.
Nodular fasciitis. This field shows the tissue culture–like appearance of nodular fasciitis.
Nodular fasciitis. Bland-looking myofibroblastic cells are loosely arranged in a fibromyxoid matrix.

Q: A small (≤ 30 mm), rapidly growing soft tissue mass that clinically develops over 2–3 months and histologically demonstrates a circumscribed proliferation of bland myofibroblasts is highly characteristic of [...].
Nodular fasciitis. The lesion is often circumscribed.
Nodular fasciitis. Bland-looking myofibroblastic cells are loosely arranged in a fibromyxoid matrix.
A: Nodular Fasciitis
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis grows rapidly and usually has a preoperative duration of ≤ 2–3 months; it often measures ≤ 30 mm on excision.
- Micro: The lesion is composed of plump, spindle-shaped cells with a tissue culture–like architecture and a variably myxoid stroma.
- Ancillary: USP6 rearrangement is a characteristic feature and can confirm the diagnosis.
Reference Gallery:
Nodular fasciitis. The lesion is often circumscribed.
Nodular fasciitis. This field shows the tissue culture–like appearance of nodular fasciitis.
Nodular fasciitis. Bland-looking myofibroblastic cells are loosely arranged in a fibromyxoid matrix.

Q: While often diagnosed by its classic microscopic appearance, the diagnosis of Nodular Fasciitis can be confirmed by identifying a characteristic rearrangement involving the [...] gene.
Nodular fasciitis. This field shows the tissue culture–like appearance of nodular fasciitis.
A: USP6
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis grows rapidly and usually has a preoperative duration of ≤ 2–3 months; it often measures ≤ 30 mm on excision.
- Micro: The lesion is composed of plump, spindle-shaped cells with a tissue culture–like architecture and a variably myxoid stroma.
- Ancillary: USP6 rearrangement is a characteristic feature and can confirm the diagnosis.
Reference Gallery:
Nodular fasciitis. The lesion is often circumscribed.
Nodular fasciitis. This field shows the tissue culture–like appearance of nodular fasciitis.
Nodular fasciitis. Bland-looking myofibroblastic cells are loosely arranged in a fibromyxoid matrix.

Q: Histologically, Solitary Fibrous Tumor typically displays a "patternless" architecture of bland spindle cells, dilated vascular spaces, and characteristic thick, [...] collagen deposition.
Solitary fibrous tumour. Salivary gland solitary fibrous tumour. Keloid-like collagen transitions into areas of more delicate, wiry collagen deposition in a salivary gland solitary fibrous tumour. There are residual entrapped ducts and acini.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this sinonasal tract tumour showing a very hypocellular pattern, with prominent keloid-like collagen deposition.
A: keloid-like
Back Extra: Solitary Fibrous Tumour
- Clinical: Patients with solitary fibrous tumour (SFT) usually present with a painless, slow-growing mass. Visual changes, pain, and proptosis may occur in orbital tumours, while sinonasal tumours can cause obstructive symptoms, epistaxis, and discharge.
- Micro: SFTs are characterized by a patternless distribution of hypocellular and hypercellular areas, with uniform, bland, syncytial spindled cells separated by dilated, angulated vascular spaces. Myxoid change and keloid-like collagen deposition can also be seen.
- Ancillary: STAT6 immunohistochemistry shows strong and diffuse nuclear expression, which is essential for diagnosing SFT. The presence of NAB2::STAT6 gene fusion can be demonstrated in selected cases.
Reference Gallery:
Solitary fibrous tumour. Solitary fibrous tumour of the parotid gland. There is an irregular but well-defined high-signal-intensity mass within the parotid gland as shown by this axial T1-weighted, fat-suppressed postcontrast MRI.
Solitary fibrous tumour. Salivary solitary fibrous tumour. At low magnification there is a well-circumscribed appearance to this cellular spindled cell neoplasm. Note the residual salivary gland tissue.
Solitary fibrous tumour. Salivary gland solitary fibrous tumour. Keloid-like collagen transitions into areas of more delicate, wiry collagen deposition in a salivary gland solitary fibrous tumour. There are residual entrapped ducts and acini.
Sinonasal tract solitary fibrous tumour. Compact, short fascicles of spindled cells are separated by open, patulous vessels showing a staghorn appearance.
Sinonasal tract solitary fibrous tumour. Wiry, refractile collagen is deposited between a modestly cellular, monotonous spindled cell neoplastic proliferation.
Sinonasal tract solitary fibrous tumour. The neoplastic cells have a syncytial quality, with bland, elongated, oval nuclei surrounded by limited cytoplasm. There is a richly collagenized stroma.
Sinonasal tract solitary fibrous tumour. There is a relatively low cellularity in this tumour showing hyperchromatic nuclei in haphazardly arranged spindled cells.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this orbital tumour showing a very tight, palisaded nuclear arrangement.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this sinonasal tract tumour showing a very hypocellular pattern, with prominent keloid-like collagen deposition.
Solitary fibrous tumour. Tumour subtypes are recognized, with a well-developed adipocytic component in this sinonasal tract tumour.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this sinonasal tract tumour showing myxoid stromal change.
Solitary fibrous tumour. STAT6 immunohistochemistry gives a strong and diffuse nuclear reaction.

Q: The dilated, angulated vascular spaces characteristically seen in the background stroma of a Solitary Fibrous Tumor are classically described as having a [...] appearance.
Sinonasal tract solitary fibrous tumour. Compact, short fascicles of spindled cells are separated by open, patulous vessels showing a staghorn appearance.
A: staghorn
Back Extra: Solitary Fibrous Tumour
- Clinical: Patients with solitary fibrous tumour (SFT) usually present with a painless, slow-growing mass. Visual changes, pain, and proptosis may occur in orbital tumours, while sinonasal tumours can cause obstructive symptoms, epistaxis, and discharge.
- Micro: SFTs are characterized by a patternless distribution of hypocellular and hypercellular areas, with uniform, bland, syncytial spindled cells separated by dilated, angulated vascular spaces. Myxoid change and keloid-like collagen deposition can also be seen.
- Ancillary: STAT6 immunohistochemistry shows strong and diffuse nuclear expression, which is essential for diagnosing SFT. The presence of NAB2::STAT6 gene fusion can be demonstrated in selected cases.
Reference Gallery:
Solitary fibrous tumour. Solitary fibrous tumour of the parotid gland. There is an irregular but well-defined high-signal-intensity mass within the parotid gland as shown by this axial T1-weighted, fat-suppressed postcontrast MRI.
Solitary fibrous tumour. Salivary solitary fibrous tumour. At low magnification there is a well-circumscribed appearance to this cellular spindled cell neoplasm. Note the residual salivary gland tissue.
Solitary fibrous tumour. Salivary gland solitary fibrous tumour. Keloid-like collagen transitions into areas of more delicate, wiry collagen deposition in a salivary gland solitary fibrous tumour. There are residual entrapped ducts and acini.
Sinonasal tract solitary fibrous tumour. Compact, short fascicles of spindled cells are separated by open, patulous vessels showing a staghorn appearance.
Sinonasal tract solitary fibrous tumour. Wiry, refractile collagen is deposited between a modestly cellular, monotonous spindled cell neoplastic proliferation.
Sinonasal tract solitary fibrous tumour. The neoplastic cells have a syncytial quality, with bland, elongated, oval nuclei surrounded by limited cytoplasm. There is a richly collagenized stroma.
Sinonasal tract solitary fibrous tumour. There is a relatively low cellularity in this tumour showing hyperchromatic nuclei in haphazardly arranged spindled cells.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this orbital tumour showing a very tight, palisaded nuclear arrangement.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this sinonasal tract tumour showing a very hypocellular pattern, with prominent keloid-like collagen deposition.
Solitary fibrous tumour. Tumour subtypes are recognized, with a well-developed adipocytic component in this sinonasal tract tumour.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this sinonasal tract tumour showing myxoid stromal change.
Solitary fibrous tumour. STAT6 immunohistochemistry gives a strong and diffuse nuclear reaction.

Q: Immunohistochemistry for Solitary Fibrous Tumor is characterized by essential, strong, and diffuse nuclear expression of [...], reflecting its underlying NAB2::STAT6 gene fusion.
Solitary fibrous tumour. STAT6 immunohistochemistry gives a strong and diffuse nuclear reaction.
A: STAT6
Back Extra: Solitary Fibrous Tumour
- Clinical: Patients with solitary fibrous tumour (SFT) usually present with a painless, slow-growing mass. Visual changes, pain, and proptosis may occur in orbital tumours, while sinonasal tumours can cause obstructive symptoms, epistaxis, and discharge.
- Micro: SFTs are characterized by a patternless distribution of hypocellular and hypercellular areas, with uniform, bland, syncytial spindled cells separated by dilated, angulated vascular spaces. Myxoid change and keloid-like collagen deposition can also be seen.
- Ancillary: STAT6 immunohistochemistry shows strong and diffuse nuclear expression, which is essential for diagnosing SFT. The presence of NAB2::STAT6 gene fusion can be demonstrated in selected cases.
Reference Gallery:
Solitary fibrous tumour. Solitary fibrous tumour of the parotid gland. There is an irregular but well-defined high-signal-intensity mass within the parotid gland as shown by this axial T1-weighted, fat-suppressed postcontrast MRI.
Solitary fibrous tumour. Salivary solitary fibrous tumour. At low magnification there is a well-circumscribed appearance to this cellular spindled cell neoplasm. Note the residual salivary gland tissue.
Solitary fibrous tumour. Salivary gland solitary fibrous tumour. Keloid-like collagen transitions into areas of more delicate, wiry collagen deposition in a salivary gland solitary fibrous tumour. There are residual entrapped ducts and acini.
Sinonasal tract solitary fibrous tumour. Compact, short fascicles of spindled cells are separated by open, patulous vessels showing a staghorn appearance.
Sinonasal tract solitary fibrous tumour. Wiry, refractile collagen is deposited between a modestly cellular, monotonous spindled cell neoplastic proliferation.
Sinonasal tract solitary fibrous tumour. The neoplastic cells have a syncytial quality, with bland, elongated, oval nuclei surrounded by limited cytoplasm. There is a richly collagenized stroma.
Sinonasal tract solitary fibrous tumour. There is a relatively low cellularity in this tumour showing hyperchromatic nuclei in haphazardly arranged spindled cells.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this orbital tumour showing a very tight, palisaded nuclear arrangement.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this sinonasal tract tumour showing a very hypocellular pattern, with prominent keloid-like collagen deposition.
Solitary fibrous tumour. Tumour subtypes are recognized, with a well-developed adipocytic component in this sinonasal tract tumour.
Solitary fibrous tumour. Tumour cellularity and patterns can vary, with this sinonasal tract tumour showing myxoid stromal change.
Solitary fibrous tumour. STAT6 immunohistochemistry gives a strong and diffuse nuclear reaction.

Q: Histologically, Myofibroma features a biphasic growth of primitive basophilic cells and eosinophilic myoid cells, commonly associated with prominent myointimal nodular proliferations termed [...].
Myofibroma. A well-defined tumour with prominent micronodular myointimal proliferations (vascular balls) surrounded by cellular areas with primitive ovoid to spindled cells and gaping vessels.
Myofibroma. Myxoid myointimal proliferation (vascular ball) closely juxtaposed to sclerotic areas.
A: vascular balls
Back Extra: Myofibroma
- Clinical: Myofibroma presents as a small, well-circumscribed, superficial dermal or subcutaneous violaceous nodule, ranging in size from < 10 mm to several centimetres. Three clinicopathological settings are recognized: solitary, multicentric, and generalized.
- Micro: Characterized by alternating bundles of primitive basophilic, small, rounded to plump spindled cells and eosinophilic myoid cells, associated with prominent thin-walled pericytoma-like vessels with frequent myointimal nodular proliferations (vascular balls).
- Ancillary: Identification of somatic or germline PDGFRB mutations may be helpful in selected cases. Infantile myofibromatosis lacks the ETV6::NTRK3 and LMNA::NTRK1 gene fusions found in infantile fibrosarcoma.
Reference Gallery:
Myofibroma. A well-defined tumour with prominent micronodular myointimal proliferations (vascular balls) surrounded by cellular areas with primitive ovoid to spindled cells and gaping vessels.
Myofibroma. Myxoid myointimal proliferation (vascular ball) closely juxtaposed to sclerotic areas.
Myofibroma. Fascicles of monomorphic primitive ovoid to spindled cells interrupted by elongated compressed vessels and focal myointimal proliferation.
Myofibroma. Cellular myofibroma with monomorphic primitive ovoid to spindled cells interrupted by pericytoma-like ectatic, thin-walled vessels.
Myofibroma. Alternating fascicles of darkly stained primitive-looking and eosinophilic (myoid) cells.
Myofibroma. Ischaemic-type necrosis may be present.
Myofibroma. Alternating eosinophilic myoid and darkly stained primitive cellular fascicles.
Myofibroma. Diffuse cellular areas lacking zonation should not be mistaken for sarcoma.
Myofibroma. SMA highlights the myoid fascicles sparing the primitive-looking cells.
Myofibroma. CT shows a contrast-enhancing, well-defined mass in the median neck closely associated with the thyroid gland.

Q: The characteristic biphasic histologic pattern of Myofibroma consists of alternating bundles of primitive basophilic cells and [...] cells, which are highlighted by smooth muscle actin (SMA) stains.
Myofibroma. Alternating fascicles of darkly stained primitive-looking and eosinophilic (myoid) cells.
Myofibroma. Alternating eosinophilic myoid and darkly stained primitive cellular fascicles.
Myofibroma. SMA highlights the myoid fascicles sparing the primitive-looking cells.
A: eosinophilic myoid
Back Extra: Myofibroma
- Clinical: Myofibroma presents as a small, well-circumscribed, superficial dermal or subcutaneous violaceous nodule, ranging in size from < 10 mm to several centimetres. Three clinicopathological settings are recognized: solitary, multicentric, and generalized.
- Micro: Characterized by alternating bundles of primitive basophilic, small, rounded to plump spindled cells and eosinophilic myoid cells, associated with prominent thin-walled pericytoma-like vessels with frequent myointimal nodular proliferations (vascular balls).
- Ancillary: Identification of somatic or germline PDGFRB mutations may be helpful in selected cases. Infantile myofibromatosis lacks the ETV6::NTRK3 and LMNA::NTRK1 gene fusions found in infantile fibrosarcoma.
Reference Gallery:
Myofibroma. A well-defined tumour with prominent micronodular myointimal proliferations (vascular balls) surrounded by cellular areas with primitive ovoid to spindled cells and gaping vessels.
Myofibroma. Myxoid myointimal proliferation (vascular ball) closely juxtaposed to sclerotic areas.
Myofibroma. Fascicles of monomorphic primitive ovoid to spindled cells interrupted by elongated compressed vessels and focal myointimal proliferation.
Myofibroma. Cellular myofibroma with monomorphic primitive ovoid to spindled cells interrupted by pericytoma-like ectatic, thin-walled vessels.
Myofibroma. Alternating fascicles of darkly stained primitive-looking and eosinophilic (myoid) cells.
Myofibroma. Ischaemic-type necrosis may be present.
Myofibroma. Alternating eosinophilic myoid and darkly stained primitive cellular fascicles.
Myofibroma. Diffuse cellular areas lacking zonation should not be mistaken for sarcoma.
Myofibroma. SMA highlights the myoid fascicles sparing the primitive-looking cells.
Myofibroma. CT shows a contrast-enhancing, well-defined mass in the median neck closely associated with the thyroid gland.

Q: Interlacing fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas, along with spindled to serpentine nuclei, are histologic hallmarks of [...].
Malignant peripheral nerve sheath tumour. Interlacing fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas.
Malignant peripheral nerve sheath tumour. Fascicles are densely cellular, and the tumour cells have hyperchromatic and spindled to serpentine nuclei and palely eosinophilic cytoplasm.
A: Malignant Peripheral Nerve Sheath Tumor
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumour (MPNST) typically presents as an enlarging, often painful mass in patients between 20 and 50 years of age, more commonly in those with neurofibromatosis type 1 (NF1).
- Micro: MPNST shows interlacing fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas, hyperchromatic and spindled to serpentine nuclei, and palely eosinophilic cytoplasm.
- Ancillary: Complete loss of staining for H3K27me3 is a helpful diagnostic feature, occurring in 50–80% of MPNSTs.
Reference Gallery:
Malignant peripheral nerve sheath tumour. Interlacing fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas.
Malignant peripheral nerve sheath tumour. Fascicles are densely cellular, and the tumour cells have hyperchromatic and spindled to serpentine nuclei and palely eosinophilic cytoplasm.
Malignant peripheral nerve sheath tumour. Complete loss of staining for H3K27me3 is a helpful diagnostic feature, occurring in 50–80% of all cases.

Q: In Malignant Peripheral Nerve Sheath Tumor, 50–80% of cases exhibit a complete diagnostic loss of immunohistochemical staining for [...].
Malignant peripheral nerve sheath tumour. Complete loss of staining for H3K27me3 is a helpful diagnostic feature, occurring in 50–80% of all cases.
A: H3K27me3
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumour (MPNST) typically presents as an enlarging, often painful mass in patients between 20 and 50 years of age, more commonly in those with neurofibromatosis type 1 (NF1).
- Micro: MPNST shows interlacing fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas, hyperchromatic and spindled to serpentine nuclei, and palely eosinophilic cytoplasm.
- Ancillary: Complete loss of staining for H3K27me3 is a helpful diagnostic feature, occurring in 50–80% of MPNSTs.
Reference Gallery:
Malignant peripheral nerve sheath tumour. Interlacing fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas.
Malignant peripheral nerve sheath tumour. Fascicles are densely cellular, and the tumour cells have hyperchromatic and spindled to serpentine nuclei and palely eosinophilic cytoplasm.
Malignant peripheral nerve sheath tumour. Complete loss of staining for H3K27me3 is a helpful diagnostic feature, occurring in 50–80% of all cases.

Q: Neurofibroma is histologically characterized by a random distribution of spindled cells exhibiting characteristic [...] nuclei set within a fibrous to collagenous stroma.
Sinonasal neurofibroma. Short intersecting fascicles of spindled cells with buckled nuclei and a background fibrous stroma.
Sinonasal neurofibroma. Spindled cells with buckled nuclei set within a collagenized background stroma. Mast cells are easily identified.
A: wavy or buckled
Back Extra: Neurofibroma
- Clinical: Patients with neurofibromas often present with a slowly growing, sometimes painful mass, and may develop motor or sensory symptoms when major nerve trunks are affected.
- Micro: Histopathology of neurofibromas shows a random distribution of spindly cells in a myxoid to collagenous stroma, with wavy and tapered nuclei and frequent mast cells.
- Ancillary: Immunohistochemistry for neurofibromas demonstrates positive staining for S100, SOX10, and NFP, with variable expression of CD34 and EMA in fibroblasts and perineurial cells.
Reference Gallery:
Sinonasal neurofibroma. Sagittal CT demonstrates a soft tissue–density mass (arrow) within the nasal cavity below the ethmoid sinus.
Sinonasal neurofibroma. Short intersecting fascicles of spindled cells with buckled nuclei and a background fibrous stroma.
Sinonasal neurofibroma. Spindled cells with buckled nuclei set within a collagenized background stroma. Mast cells are easily identified.
Sinonasal neurofibroma. The spindled cells are positive for S100 (shown), SOX10, and NFP.

Q: Neurofibroma features spindled cells that typically demonstrate positive immunohistochemical staining for SOX10, NFP, and [...].
Sinonasal neurofibroma. The spindled cells are positive for S100 (shown), SOX10, and NFP.
A: S100
Back Extra: Neurofibroma
- Clinical: Patients with neurofibromas often present with a slowly growing, sometimes painful mass, and may develop motor or sensory symptoms when major nerve trunks are affected.
- Micro: Histopathology of neurofibromas shows a random distribution of spindly cells in a myxoid to collagenous stroma, with wavy and tapered nuclei and frequent mast cells.
- Ancillary: Immunohistochemistry for neurofibromas demonstrates positive staining for S100, SOX10, and NFP, with variable expression of CD34 and EMA in fibroblasts and perineurial cells.
Reference Gallery:
Sinonasal neurofibroma. Sagittal CT demonstrates a soft tissue–density mass (arrow) within the nasal cavity below the ethmoid sinus.
Sinonasal neurofibroma. Short intersecting fascicles of spindled cells with buckled nuclei and a background fibrous stroma.
Sinonasal neurofibroma. Spindled cells with buckled nuclei set within a collagenized background stroma. Mast cells are easily identified.
Sinonasal neurofibroma. The spindled cells are positive for S100 (shown), SOX10, and NFP.

Q: Neurofibroma can present radiographically as a soft tissue–density mass, and its histopathologic stroma characteristically contains interspersed inflammatory cells, most notably frequent [...].
Sinonasal neurofibroma. Sagittal CT demonstrates a soft tissue–density mass (arrow) within the nasal cavity below the ethmoid sinus.
Sinonasal neurofibroma. Spindled cells with buckled nuclei set within a collagenized background stroma. Mast cells are easily identified.
A: mast cells
Back Extra: Neurofibroma
- Clinical: Patients with neurofibromas often present with a slowly growing, sometimes painful mass, and may develop motor or sensory symptoms when major nerve trunks are affected.
- Micro: Histopathology of neurofibromas shows a random distribution of spindly cells in a myxoid to collagenous stroma, with wavy and tapered nuclei and frequent mast cells.
- Ancillary: Immunohistochemistry for neurofibromas demonstrates positive staining for S100, SOX10, and NFP, with variable expression of CD34 and EMA in fibroblasts and perineurial cells.
Reference Gallery:
Sinonasal neurofibroma. Sagittal CT demonstrates a soft tissue–density mass (arrow) within the nasal cavity below the ethmoid sinus.
Sinonasal neurofibroma. Short intersecting fascicles of spindled cells with buckled nuclei and a background fibrous stroma.
Sinonasal neurofibroma. Spindled cells with buckled nuclei set within a collagenized background stroma. Mast cells are easily identified.
Sinonasal neurofibroma. The spindled cells are positive for S100 (shown), SOX10, and NFP.

Q: A frequently painful subtype of Neuroma that microscopically features disorganized, sprouting fascicles of Schwann cells haphazardly arranged in a fibromyxoid stroma is known as a [...] neuroma.
Traumatic neuroma. Sprouting fascicles of Schwann cells haphazardly arranged in a fibromyxoid stroma.
A: traumatic
Back Extra: Neuroma
- Clinical: Neuromas often present as single nodules (traumatic neuroma, solitary circumscribed neuroma) or multiple nodules (PIK3CA neuroma), and many traumatic neuromas are painful.
- Micro: Traumatic neuromas show disorganized Schwann cell fascicles, while solitary circumscribed neuromas are characterized by intersecting Schwann cell fascicles with nerve axons and cracking artefacts.
- Ancillary: PIK3CA neuromas are associated with PIK3CA variants in the majority of cases.
Reference Gallery:
Traumatic neuroma. Sprouting fascicles of Schwann cells haphazardly arranged in a fibromyxoid stroma.
Solitary circumscribed neuroma. A fungating neural lesion characterized by intersecting Schwann cell fascicles with cracking artefacts.
Oral pseudoperineurioma. A fibrous hyperplastic lesion with fascicles of nerves in the stroma.
Oral pseudoperineurioma. Pseudo–onion bulb perineurial cell proliferation. Single or (mostly) double layers of perineurial cells surrounding individual axons.
Oral pseudoperineurioma. Pseudo–onion bulb perineurial cell proliferation. Single or (mostly) double layers of perineurial cells surrounding individual axons in a collagenous hyperplastic stroma (H&E).
Oral pseudoperineurioma. EMA highlights multiple pseudo–onion bulbs composed of perineurial cells within a nerve partially surrounded by perineurium.
PIK3CA neuroma. Nodular lesions on the lip.
PIK3CA neuroma. Unilateral enlargement of the tongue with prominent papillae.
PIK3CA neuroma. Biopsy of the labial lesion revealed expanded nerves showing perineurial proliferation, consistent with oral pseudoperineurioma.

Q: The solitary circumscribed Neuroma is characterized microscopically by intersecting fascicles of Schwann cells and nerve axons separated by distinctive [...].
Solitary circumscribed neuroma. A fungating neural lesion characterized by intersecting Schwann cell fascicles with cracking artefacts.
A: cracking artifacts
Back Extra: Neuroma
- Clinical: Neuromas often present as single nodules (traumatic neuroma, solitary circumscribed neuroma) or multiple nodules (PIK3CA neuroma), and many traumatic neuromas are painful.
- Micro: Traumatic neuromas show disorganized Schwann cell fascicles, while solitary circumscribed neuromas are characterized by intersecting Schwann cell fascicles with nerve axons and cracking artefacts.
- Ancillary: PIK3CA neuromas are associated with PIK3CA variants in the majority of cases.
Reference Gallery:
Traumatic neuroma. Sprouting fascicles of Schwann cells haphazardly arranged in a fibromyxoid stroma.
Solitary circumscribed neuroma. A fungating neural lesion characterized by intersecting Schwann cell fascicles with cracking artefacts.
Oral pseudoperineurioma. A fibrous hyperplastic lesion with fascicles of nerves in the stroma.
Oral pseudoperineurioma. Pseudo–onion bulb perineurial cell proliferation. Single or (mostly) double layers of perineurial cells surrounding individual axons.
Oral pseudoperineurioma. Pseudo–onion bulb perineurial cell proliferation. Single or (mostly) double layers of perineurial cells surrounding individual axons in a collagenous hyperplastic stroma (H&E).
Oral pseudoperineurioma. EMA highlights multiple pseudo–onion bulbs composed of perineurial cells within a nerve partially surrounded by perineurium.
PIK3CA neuroma. Nodular lesions on the lip.
PIK3CA neuroma. Unilateral enlargement of the tongue with prominent papillae.
PIK3CA neuroma. Biopsy of the labial lesion revealed expanded nerves showing perineurial proliferation, consistent with oral pseudoperineurioma.

Q: A [...] Neuroma often presents clinically with multiple nodules or unilateral tongue enlargement, and microscopically features expanded nerves with pseudo-onion bulb perineurial proliferation.
PIK3CA neuroma. Nodular lesions on the lip.
PIK3CA neuroma. Unilateral enlargement of the tongue with prominent papillae.
PIK3CA neuroma. Biopsy of the labial lesion revealed expanded nerves showing perineurial proliferation, consistent with oral pseudoperineurioma.
A: PIK3CA
Back Extra: Neuroma
- Clinical: Neuromas often present as single nodules (traumatic neuroma, solitary circumscribed neuroma) or multiple nodules (PIK3CA neuroma), and many traumatic neuromas are painful.
- Micro: Traumatic neuromas show disorganized Schwann cell fascicles, while solitary circumscribed neuromas are characterized by intersecting Schwann cell fascicles with nerve axons and cracking artefacts.
- Ancillary: PIK3CA neuromas are associated with PIK3CA variants in the majority of cases.
Reference Gallery:
Traumatic neuroma. Sprouting fascicles of Schwann cells haphazardly arranged in a fibromyxoid stroma.
Solitary circumscribed neuroma. A fungating neural lesion characterized by intersecting Schwann cell fascicles with cracking artefacts.
Oral pseudoperineurioma. A fibrous hyperplastic lesion with fascicles of nerves in the stroma.
Oral pseudoperineurioma. Pseudo–onion bulb perineurial cell proliferation. Single or (mostly) double layers of perineurial cells surrounding individual axons.
Oral pseudoperineurioma. Pseudo–onion bulb perineurial cell proliferation. Single or (mostly) double layers of perineurial cells surrounding individual axons in a collagenous hyperplastic stroma (H&E).
Oral pseudoperineurioma. EMA highlights multiple pseudo–onion bulbs composed of perineurial cells within a nerve partially surrounded by perineurium.
PIK3CA neuroma. Nodular lesions on the lip.
PIK3CA neuroma. Unilateral enlargement of the tongue with prominent papillae.
PIK3CA neuroma. Biopsy of the labial lesion revealed expanded nerves showing perineurial proliferation, consistent with oral pseudoperineurioma.

Q: Microscopically, Schwannoma classically exhibits hypercellular Antoni A areas with nuclear palisading known as [...], juxtaposed with hypocellular, myxoid Antoni B areas.
Sinonasal schwannoma. Hypocellular and hypercellular areas are seen in this schwannoma.
Sinonasal schwannoma. There is an Antoni A area juxtaposed to an Antoni B area, with myxoid change noted in the stroma.
A: Verocay bodies
Back Extra: Schwannoma
- Clinical: Patients present with a slowly growing, sometimes painful mass, often with a well-circumscribed, expansile tumour on imaging.
- Micro: Schwannomas show hypercellular Antoni A areas with nuclear palisading (Verocay bodies) and hypocellular Antoni B areas with myxoid changes.
- Ancillary: Immunohistochemistry shows diffuse S100 and SOX10 positivity, and genetic findings may include NF2 inactivating mutations.
Reference Gallery:
Schwannoma. Sinonasal schwannoma. T1-weighted fat-suppressed coronal MRI shows a mass expanding into the skull base. It is not uncommon for schwannoma to grow through foramina.
Schwannoma. Schwannoma of the parapharyngeal space. There is a well-circumscribed mass in the parapharyngeal space, showing increased intensity on this axial T2-weighted fast spin echo image.
Sinonasal schwannoma. Hypocellular and hypercellular areas are seen in this schwannoma.
Sinonasal schwannoma. There is a hypercellular spindled cell population below an intact respiratory epithelium. The nuclei are wavy to buckled.
Oral schwannoma. Fascicles of spindled neoplastic cells are seen adjacent to vessels that have a peritheliomatous hyalinization.
Sinonasal schwannoma. There is an Antoni A area juxtaposed to an Antoni B area, with myxoid change noted in the stroma.
Sinonasal schwannoma. The spindled cell proliferation is intimately associated with inflammatory cells as well as vessels with hyalinization.
Sinonasal schwannoma. Ancient change, identified by remarkably pleomorphic-appearing nuclei, is a finding of degeneration in schwannoma.
Sinonasal schwannoma. The neoplastic cells show strong and diffuse nuclear and cytoplasmic S100 immunoreactivity.
Sinonasal schwannoma. The neoplastic cells show strong and diffuse nuclear SOX10 immunoreactivity.
Schwannoma. This Giemsa-stained smear is cellular, demonstrating cohesive syncytial fragments of bland spindle cells. The tumour cells are wavy, with convoluted nuclei.
Oral schwannoma. A clinical photograph of a submucosal lateral tongue nodule.

Q: By immunohistochemistry, the neoplastic spindle cells of a Schwannoma characteristically show strong and diffuse positivity for SOX10 and [...].
Sinonasal schwannoma. The neoplastic cells show strong and diffuse nuclear and cytoplasmic S100 immunoreactivity.
Sinonasal schwannoma. The neoplastic cells show strong and diffuse nuclear SOX10 immunoreactivity.
A: S100
Back Extra: Schwannoma
- Clinical: Patients present with a slowly growing, sometimes painful mass, often with a well-circumscribed, expansile tumour on imaging.
- Micro: Schwannomas show hypercellular Antoni A areas with nuclear palisading (Verocay bodies) and hypocellular Antoni B areas with myxoid changes.
- Ancillary: Immunohistochemistry shows diffuse S100 and SOX10 positivity, and genetic findings may include NF2 inactivating mutations.
Reference Gallery:
Schwannoma. Sinonasal schwannoma. T1-weighted fat-suppressed coronal MRI shows a mass expanding into the skull base. It is not uncommon for schwannoma to grow through foramina.
Schwannoma. Schwannoma of the parapharyngeal space. There is a well-circumscribed mass in the parapharyngeal space, showing increased intensity on this axial T2-weighted fast spin echo image.
Sinonasal schwannoma. Hypocellular and hypercellular areas are seen in this schwannoma.
Sinonasal schwannoma. There is a hypercellular spindled cell population below an intact respiratory epithelium. The nuclei are wavy to buckled.
Oral schwannoma. Fascicles of spindled neoplastic cells are seen adjacent to vessels that have a peritheliomatous hyalinization.
Sinonasal schwannoma. There is an Antoni A area juxtaposed to an Antoni B area, with myxoid change noted in the stroma.
Sinonasal schwannoma. The spindled cell proliferation is intimately associated with inflammatory cells as well as vessels with hyalinization.
Sinonasal schwannoma. Ancient change, identified by remarkably pleomorphic-appearing nuclei, is a finding of degeneration in schwannoma.
Sinonasal schwannoma. The neoplastic cells show strong and diffuse nuclear and cytoplasmic S100 immunoreactivity.
Sinonasal schwannoma. The neoplastic cells show strong and diffuse nuclear SOX10 immunoreactivity.
Schwannoma. This Giemsa-stained smear is cellular, demonstrating cohesive syncytial fragments of bland spindle cells. The tumour cells are wavy, with convoluted nuclei.
Oral schwannoma. A clinical photograph of a submucosal lateral tongue nodule.

Q: A known degenerative finding in Schwannoma is the presence of remarkably pleomorphic-appearing, atypical nuclei without mitoses, a feature referred to as [...].
Sinonasal schwannoma. Ancient change, identified by remarkably pleomorphic-appearing nuclei, is a finding of degeneration in schwannoma.
A: ancient change
Back Extra: Schwannoma
- Clinical: Patients present with a slowly growing, sometimes painful mass, often with a well-circumscribed, expansile tumour on imaging.
- Micro: Schwannomas show hypercellular Antoni A areas with nuclear palisading (Verocay bodies) and hypocellular Antoni B areas with myxoid changes.
- Ancillary: Immunohistochemistry shows diffuse S100 and SOX10 positivity, and genetic findings may include NF2 inactivating mutations.
Reference Gallery:
Schwannoma. Sinonasal schwannoma. T1-weighted fat-suppressed coronal MRI shows a mass expanding into the skull base. It is not uncommon for schwannoma to grow through foramina.
Schwannoma. Schwannoma of the parapharyngeal space. There is a well-circumscribed mass in the parapharyngeal space, showing increased intensity on this axial T2-weighted fast spin echo image.
Sinonasal schwannoma. Hypocellular and hypercellular areas are seen in this schwannoma.
Sinonasal schwannoma. There is a hypercellular spindled cell population below an intact respiratory epithelium. The nuclei are wavy to buckled.
Oral schwannoma. Fascicles of spindled neoplastic cells are seen adjacent to vessels that have a peritheliomatous hyalinization.
Sinonasal schwannoma. There is an Antoni A area juxtaposed to an Antoni B area, with myxoid change noted in the stroma.
Sinonasal schwannoma. The spindled cell proliferation is intimately associated with inflammatory cells as well as vessels with hyalinization.
Sinonasal schwannoma. Ancient change, identified by remarkably pleomorphic-appearing nuclei, is a finding of degeneration in schwannoma.
Sinonasal schwannoma. The neoplastic cells show strong and diffuse nuclear and cytoplasmic S100 immunoreactivity.
Sinonasal schwannoma. The neoplastic cells show strong and diffuse nuclear SOX10 immunoreactivity.
Schwannoma. This Giemsa-stained smear is cellular, demonstrating cohesive syncytial fragments of bland spindle cells. The tumour cells are wavy, with convoluted nuclei.
Oral schwannoma. A clinical photograph of a submucosal lateral tongue nodule.

Q: Adult-type Rhabdomyoma is classically characterized by large polygonal cells with focally retracted clear cytoplasm, creating a distinctive [...] appearance.
Rhabdomyoma, adult type. Intermediate-power view demonstrates polygonal, plump cells with focally retracted, clear cytoplasm creating a spider-web appearance.
Rhabdomyoma, adult type. High-power view showing cytoplasmic processes creating a spider-web appearance. Note the delicate cross-striations in the cytoplasm of the polygonal cells.
A: spider-web
Back Extra: Rhabdomyoma
- Clinical: Patients with Rhabdomyoma often present with a slowly growing mass, particularly in the head and neck region.
- Micro: Adult-type Rhabdomyoma (ARM) is characterized by large polygonal cells with abundant eosinophilic or vacuolated cytoplasm and peripherally located nuclei.
- Ancillary: Immunohistochemistry (IHC) shows strong and diffuse cytoplasmic expression of desmin in both ARM and fetal-type Rhabdomyoma (FRM).
Reference Gallery:
Rhabdomyoma, adult type. Intermediate-power view demonstrates polygonal, plump cells with focally retracted, clear cytoplasm creating a spider-web appearance.
Rhabdomyoma, adult type. High-power view showing cytoplasmic processes creating a spider-web appearance. Note the delicate cross-striations in the cytoplasm of the polygonal cells.
Rhabdomyoma, fetal type. There are primitive-appearing spindled cells and isolated strap-type cells with eosinophilic, eccentric cytoplasm.
Rhabdomyoma, fetal type. The primitive-appearing cells may dissect between muscle bundles, but they lack lymphovascular invasion, tumour necrosis, and atypical mitoses.
Rhabdomyoma, fetal type. There is a monotony to the neoplastic cells, which have a syncytial appearance with slightly plasmacytoid cells. Occasional intranuclear cytoplasmic inclusions are present.
Rhabdomyoma, fetal type. The neoplastic cells demonstrate a strong and diffuse cytoplasmic expression of desmin, highlighting the elongated cytoplasmic processes.
Fetal rhabdomyoma. A primitive-appearing but non-atypical spindled to epithelioid proliferation of polygonal to spindled cells adjacent to minor mucoserous glands and skeletal muscle.
Rhabdomyoma, fetal type. Cytologically bland spindled cells are arranged in loose fascicles in a collagenous stroma.
Rhabdomyoma, fetal type. Mature-appearing rhabdomyoblasts are seen in an inflammatory background. There is no atypia or mitotic activity.

Q: Microscopically, fetal-type Rhabdomyoma consists of a bland proliferation of primitive-appearing spindled cells admixed with isolated, eosinophilic [...] cells.
Rhabdomyoma, fetal type. There are primitive-appearing spindled cells and isolated strap-type cells with eosinophilic, eccentric cytoplasm.
A: strap-type
Back Extra: Rhabdomyoma
- Clinical: Patients with Rhabdomyoma often present with a slowly growing mass, particularly in the head and neck region.
- Micro: Adult-type Rhabdomyoma (ARM) is characterized by large polygonal cells with abundant eosinophilic or vacuolated cytoplasm and peripherally located nuclei.
- Ancillary: Immunohistochemistry (IHC) shows strong and diffuse cytoplasmic expression of desmin in both ARM and fetal-type Rhabdomyoma (FRM).
Reference Gallery:
Rhabdomyoma, adult type. Intermediate-power view demonstrates polygonal, plump cells with focally retracted, clear cytoplasm creating a spider-web appearance.
Rhabdomyoma, adult type. High-power view showing cytoplasmic processes creating a spider-web appearance. Note the delicate cross-striations in the cytoplasm of the polygonal cells.
Rhabdomyoma, fetal type. There are primitive-appearing spindled cells and isolated strap-type cells with eosinophilic, eccentric cytoplasm.
Rhabdomyoma, fetal type. The primitive-appearing cells may dissect between muscle bundles, but they lack lymphovascular invasion, tumour necrosis, and atypical mitoses.
Rhabdomyoma, fetal type. There is a monotony to the neoplastic cells, which have a syncytial appearance with slightly plasmacytoid cells. Occasional intranuclear cytoplasmic inclusions are present.
Rhabdomyoma, fetal type. The neoplastic cells demonstrate a strong and diffuse cytoplasmic expression of desmin, highlighting the elongated cytoplasmic processes.
Fetal rhabdomyoma. A primitive-appearing but non-atypical spindled to epithelioid proliferation of polygonal to spindled cells adjacent to minor mucoserous glands and skeletal muscle.
Rhabdomyoma, fetal type. Cytologically bland spindled cells are arranged in loose fascicles in a collagenous stroma.
Rhabdomyoma, fetal type. Mature-appearing rhabdomyoblasts are seen in an inflammatory background. There is no atypia or mitotic activity.

Q: Immunohistochemistry for Rhabdomyoma (both adult and fetal types) demonstrates strong and diffuse cytoplasmic expression of the muscle marker [...].
Rhabdomyoma, fetal type. The neoplastic cells demonstrate a strong and diffuse cytoplasmic expression of desmin, highlighting the elongated cytoplasmic processes.
A: desmin
Back Extra: Rhabdomyoma
- Clinical: Patients with Rhabdomyoma often present with a slowly growing mass, particularly in the head and neck region.
- Micro: Adult-type Rhabdomyoma (ARM) is characterized by large polygonal cells with abundant eosinophilic or vacuolated cytoplasm and peripherally located nuclei.
- Ancillary: Immunohistochemistry (IHC) shows strong and diffuse cytoplasmic expression of desmin in both ARM and fetal-type Rhabdomyoma (FRM).
Reference Gallery:
Rhabdomyoma, adult type. Intermediate-power view demonstrates polygonal, plump cells with focally retracted, clear cytoplasm creating a spider-web appearance.
Rhabdomyoma, adult type. High-power view showing cytoplasmic processes creating a spider-web appearance. Note the delicate cross-striations in the cytoplasm of the polygonal cells.
Rhabdomyoma, fetal type. There are primitive-appearing spindled cells and isolated strap-type cells with eosinophilic, eccentric cytoplasm.
Rhabdomyoma, fetal type. The primitive-appearing cells may dissect between muscle bundles, but they lack lymphovascular invasion, tumour necrosis, and atypical mitoses.
Rhabdomyoma, fetal type. There is a monotony to the neoplastic cells, which have a syncytial appearance with slightly plasmacytoid cells. Occasional intranuclear cytoplasmic inclusions are present.
Rhabdomyoma, fetal type. The neoplastic cells demonstrate a strong and diffuse cytoplasmic expression of desmin, highlighting the elongated cytoplasmic processes.
Fetal rhabdomyoma. A primitive-appearing but non-atypical spindled to epithelioid proliferation of polygonal to spindled cells adjacent to minor mucoserous glands and skeletal muscle.
Rhabdomyoma, fetal type. Cytologically bland spindled cells are arranged in loose fascicles in a collagenous stroma.
Rhabdomyoma, fetal type. Mature-appearing rhabdomyoblasts are seen in an inflammatory background. There is no atypia or mitotic activity.

Q: In the embryonal subtype of rhabdomyosarcoma, the diagnosis is heavily supported by the presence of elongated cells with abundant eosinophilic cytoplasm, known as [...], which may occasionally exhibit focal cross-striations.
Embryonal rhabdomyosarcoma. A pleomorphic spindled cell population is noted adjacent to the cartilage in this ear embryonal rhabdomyosarcoma. Strap cells are present, a finding that helps to confirm a rhabdomyosarcoma diagnosis.
Embryonal rhabdomyosarcoma. Short fascicles are composed of spindled cells with eosinophilic cytoplasm showing focal cross-striations in this oral embryonal rhabdomyosarcoma. There is easily identified pleomorphism.
A: strap cells
Back Extra: Rhabdomyosarcoma
- Clinical: Rhabdomyosarcoma often presents with nonspecific symptoms, leading to delayed diagnosis. Metastatic disease is frequently present at diagnosis (25–30%).
- Micro: Sinonasal alveolar rhabdomyosarcoma shows neoplastic cells with a high N:C ratio, surrounded by minor mucoserous glands, and often presents with a dyscohesive appearance.
- Ancillary: Rhabdomyosarcoma may show aberrant coexpression with CAM5.2 and synaptophysin, which can cause diagnostic challenges without a comprehensive immunohistochemistry panel.
Reference Gallery:
Sinonasal rhabdomyosarcoma. CT demonstrates a large, destructive sinonasal tract mass (between black and white arrows), present for several months.
Sinonasal alveolar rhabdomyosarcoma. A dyscohesive appearance shows neoplastic cells falling from the adjacent fibrous tissue septa into the centre of the alveolar structures. The neoplastic cells have a very high N:C ratio.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells are small with slightly cleared cytoplasm. They surround and entomb the native minor mucoserous glands.
Sinonasal alveolar rhabdomyosarcoma. At high magnification, the rhabdoid appearance of the cells can be seen, with opaque, eccentric cytoplasm. Mitotic figures are easily identified.
Sinonasal alveolar rhabdomyosarcoma. There is an intact respiratory epithelium. The stroma is busy, filled with small cells showing a high N:C ratio and rhabdoid features. Sometimes this appearance may mimic inflammatory sinonasal polyps.
Embryonal rhabdomyosarcoma. A pleomorphic spindled cell population is noted adjacent to the cartilage in this ear embryonal rhabdomyosarcoma. Strap cells are present, a finding that helps to confirm a rhabdomyosarcoma diagnosis.
Embryonal rhabdomyosarcoma. Short fascicles are composed of spindled cells with eosinophilic cytoplasm showing focal cross-striations in this oral embryonal rhabdomyosarcoma. There is easily identified pleomorphism.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells demonstrate a strong and diffuse nuclear reaction for myogenin.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells of rhabdomyosarcoma may show aberrant coexpression with CAM5.2, a finding that may cause diagnostic problems if a panel of immunohistochemistry studies is not performed.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells of rhabdomyosarcoma may show aberrant coexpression with synaptophysin, a finding that may cause diagnostic problems if a panel of immunohistochemistry studies is not performed.
Sinonasal alveolar rhabdomyosarcoma. Aspiration smears demonstrate multinucleated tumour cells along with dispersed single cells showing eccentric cytoplasm.
Spindle cell rhabdomyosarcoma. Spindle-shaped tumour cells have hyperchromatic nuclei and are arranged in fascicular patterns.

Q: The neoplastic cells of rhabdomyosarcoma characteristically demonstrate strong and diffuse nuclear reactivity for [...], a key skeletal muscle regulatory transcription factor.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells demonstrate a strong and diffuse nuclear reaction for myogenin.
A: myogenin
Back Extra: Rhabdomyosarcoma
- Clinical: Rhabdomyosarcoma often presents with nonspecific symptoms, leading to delayed diagnosis. Metastatic disease is frequently present at diagnosis (25–30%).
- Micro: Sinonasal alveolar rhabdomyosarcoma shows neoplastic cells with a high N:C ratio, surrounded by minor mucoserous glands, and often presents with a dyscohesive appearance.
- Ancillary: Rhabdomyosarcoma may show aberrant coexpression with CAM5.2 and synaptophysin, which can cause diagnostic challenges without a comprehensive immunohistochemistry panel.
Reference Gallery:
Sinonasal rhabdomyosarcoma. CT demonstrates a large, destructive sinonasal tract mass (between black and white arrows), present for several months.
Sinonasal alveolar rhabdomyosarcoma. A dyscohesive appearance shows neoplastic cells falling from the adjacent fibrous tissue septa into the centre of the alveolar structures. The neoplastic cells have a very high N:C ratio.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells are small with slightly cleared cytoplasm. They surround and entomb the native minor mucoserous glands.
Sinonasal alveolar rhabdomyosarcoma. At high magnification, the rhabdoid appearance of the cells can be seen, with opaque, eccentric cytoplasm. Mitotic figures are easily identified.
Sinonasal alveolar rhabdomyosarcoma. There is an intact respiratory epithelium. The stroma is busy, filled with small cells showing a high N:C ratio and rhabdoid features. Sometimes this appearance may mimic inflammatory sinonasal polyps.
Embryonal rhabdomyosarcoma. A pleomorphic spindled cell population is noted adjacent to the cartilage in this ear embryonal rhabdomyosarcoma. Strap cells are present, a finding that helps to confirm a rhabdomyosarcoma diagnosis.
Embryonal rhabdomyosarcoma. Short fascicles are composed of spindled cells with eosinophilic cytoplasm showing focal cross-striations in this oral embryonal rhabdomyosarcoma. There is easily identified pleomorphism.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells demonstrate a strong and diffuse nuclear reaction for myogenin.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells of rhabdomyosarcoma may show aberrant coexpression with CAM5.2, a finding that may cause diagnostic problems if a panel of immunohistochemistry studies is not performed.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells of rhabdomyosarcoma may show aberrant coexpression with synaptophysin, a finding that may cause diagnostic problems if a panel of immunohistochemistry studies is not performed.
Sinonasal alveolar rhabdomyosarcoma. Aspiration smears demonstrate multinucleated tumour cells along with dispersed single cells showing eccentric cytoplasm.
Spindle cell rhabdomyosarcoma. Spindle-shaped tumour cells have hyperchromatic nuclei and are arranged in fascicular patterns.

Q: A major diagnostic pitfall in evaluating poorly differentiated cases of rhabdomyosarcoma is the potential for aberrant coexpression of epithelial markers (e.g., CAM5.2) and the neuroendocrine marker [...], necessitating a comprehensive immunohistochemistry panel.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells of rhabdomyosarcoma may show aberrant coexpression with CAM5.2, a finding that may cause diagnostic problems if a panel of immunohistochemistry studies is not performed.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells of rhabdomyosarcoma may show aberrant coexpression with synaptophysin, a finding that may cause diagnostic problems if a panel of immunohistochemistry studies is not performed.
A: synaptophysin
Back Extra: Rhabdomyosarcoma
- Clinical: Rhabdomyosarcoma often presents with nonspecific symptoms, leading to delayed diagnosis. Metastatic disease is frequently present at diagnosis (25–30%).
- Micro: Sinonasal alveolar rhabdomyosarcoma shows neoplastic cells with a high N:C ratio, surrounded by minor mucoserous glands, and often presents with a dyscohesive appearance.
- Ancillary: Rhabdomyosarcoma may show aberrant coexpression with CAM5.2 and synaptophysin, which can cause diagnostic challenges without a comprehensive immunohistochemistry panel.
Reference Gallery:
Sinonasal rhabdomyosarcoma. CT demonstrates a large, destructive sinonasal tract mass (between black and white arrows), present for several months.
Sinonasal alveolar rhabdomyosarcoma. A dyscohesive appearance shows neoplastic cells falling from the adjacent fibrous tissue septa into the centre of the alveolar structures. The neoplastic cells have a very high N:C ratio.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells are small with slightly cleared cytoplasm. They surround and entomb the native minor mucoserous glands.
Sinonasal alveolar rhabdomyosarcoma. At high magnification, the rhabdoid appearance of the cells can be seen, with opaque, eccentric cytoplasm. Mitotic figures are easily identified.
Sinonasal alveolar rhabdomyosarcoma. There is an intact respiratory epithelium. The stroma is busy, filled with small cells showing a high N:C ratio and rhabdoid features. Sometimes this appearance may mimic inflammatory sinonasal polyps.
Embryonal rhabdomyosarcoma. A pleomorphic spindled cell population is noted adjacent to the cartilage in this ear embryonal rhabdomyosarcoma. Strap cells are present, a finding that helps to confirm a rhabdomyosarcoma diagnosis.
Embryonal rhabdomyosarcoma. Short fascicles are composed of spindled cells with eosinophilic cytoplasm showing focal cross-striations in this oral embryonal rhabdomyosarcoma. There is easily identified pleomorphism.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells demonstrate a strong and diffuse nuclear reaction for myogenin.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells of rhabdomyosarcoma may show aberrant coexpression with CAM5.2, a finding that may cause diagnostic problems if a panel of immunohistochemistry studies is not performed.
Sinonasal alveolar rhabdomyosarcoma. The neoplastic cells of rhabdomyosarcoma may show aberrant coexpression with synaptophysin, a finding that may cause diagnostic problems if a panel of immunohistochemistry studies is not performed.
Sinonasal alveolar rhabdomyosarcoma. Aspiration smears demonstrate multinucleated tumour cells along with dispersed single cells showing eccentric cytoplasm.
Spindle cell rhabdomyosarcoma. Spindle-shaped tumour cells have hyperchromatic nuclei and are arranged in fascicular patterns.

Q: The definitive ancillary test for an EBV-associated smooth muscle tumor is in situ hybridization demonstrating strong nuclear positivity for [...].
EBV-associated smooth muscle tumour. The neoplastic cells demonstrate a strong nuclear reaction for EBV-encoded small RNA (EBER) by in situ hybridization.
A: EBER (EBV-encoded small RNA)
Back Extra: EBV-associated smooth muscle tumour
- Clinical: EBV-associated smooth muscle tumour often presents in immunosuppressed patients, with symptoms such as dysphonia, hoarseness, dyspnoea, and pain.
- Micro: The tumour is characterized by intersecting fascicles of spindle cells with eosinophilic cytoplasm and blunt-ended nuclei, and can also contain epithelioid cells.
- Ancillary: Diagnosis is confirmed by strong nuclear positivity for EBV-encoded small RNA (EBER) by in situ hybridization.
Reference Gallery:
EBV-associated smooth muscle tumour. An endoscopic view of a polypoid projection arising from the glottis.
EBV-associated smooth muscle tumour. There is an intact squamous epithelium overlying this spindled to primitive-appearing neoplasm of the larynx.
EBV-associated smooth muscle tumour. Interlacing fascicles of spindled neoplastic cells are identified in this field of the tumour.
EBV-associated smooth muscle tumour. An epithelioid to primitive appearance is noted in these neoplastic cells with a high N:C ratio and open, vesicular nuclear chromatin.
EBV-associated smooth muscle tumour. The neoplastic cells are variably immunoreactive for SMMHC.
EBV-associated smooth muscle tumour. The neoplastic cells demonstrate a strong nuclear reaction for EBV-encoded small RNA (EBER) by in situ hybridization.

Q: In an immunosuppressed patient, a spindle cell neoplasm showing intersecting fascicles, smooth muscle myosin heavy chain (SMMHC) immunoreactivity, and strong nuclear EBER positivity is diagnostic of an [...].
EBV-associated smooth muscle tumour. Interlacing fascicles of spindled neoplastic cells are identified in this field of the tumour.
EBV-associated smooth muscle tumour. The neoplastic cells are variably immunoreactive for SMMHC.
EBV-associated smooth muscle tumour. The neoplastic cells demonstrate a strong nuclear reaction for EBV-encoded small RNA (EBER) by in situ hybridization.
A: EBV-associated smooth muscle tumor
Back Extra: EBV-associated smooth muscle tumour
- Clinical: EBV-associated smooth muscle tumour often presents in immunosuppressed patients, with symptoms such as dysphonia, hoarseness, dyspnoea, and pain.
- Micro: The tumour is characterized by intersecting fascicles of spindle cells with eosinophilic cytoplasm and blunt-ended nuclei, and can also contain epithelioid cells.
- Ancillary: Diagnosis is confirmed by strong nuclear positivity for EBV-encoded small RNA (EBER) by in situ hybridization.
Reference Gallery:
EBV-associated smooth muscle tumour. An endoscopic view of a polypoid projection arising from the glottis.
EBV-associated smooth muscle tumour. There is an intact squamous epithelium overlying this spindled to primitive-appearing neoplasm of the larynx.
EBV-associated smooth muscle tumour. Interlacing fascicles of spindled neoplastic cells are identified in this field of the tumour.
EBV-associated smooth muscle tumour. An epithelioid to primitive appearance is noted in these neoplastic cells with a high N:C ratio and open, vesicular nuclear chromatin.
EBV-associated smooth muscle tumour. The neoplastic cells are variably immunoreactive for SMMHC.
EBV-associated smooth muscle tumour. The neoplastic cells demonstrate a strong nuclear reaction for EBV-encoded small RNA (EBER) by in situ hybridization.

Q: Microscopically, the conventional form of Leiomyoma and Angioleiomyoma is characterized by bland spindled cells arranged in [...].
Leiomyoma. Interlacing fascicles of smooth muscle cells are seen in this leiomyoma. The nuclei are bland.
Leiomyoma. Fascicles of spindled leiomyoma cells show cytoplasmic vacuoles, some adjacent to bland nuclei.
A: intersecting fascicles
Leiomyoma and Angioleiomyoma
- Clinical: Leiomyomas and angioleiomyomas cause soft tissue swellings and nasal or airway obstruction, with equal sex distribution and an excellent prognosis.
- Micro: Leiomyomas show bland, spindled cells arranged in intersecting fascicles, while angioleiomyomas have a prominent vasculature surrounded by smooth muscle cells.
- Ancillary: Leiomyomas and angioleiomyomas express smooth muscle markers (α-SMA, desmin) but are negative for HMB45, SOX10, and S100.
Reference Gallery:
Sinonasal leiomyoma. CT demonstrating a well-circumscribed mass in the anterior nasal cavity (arrow).
Angioleiomyoma. Vascular channels are surrounded by a spindle cell proliferation in this nasal cavity angioleiomyoma.
Angioleiomyoma. An angioleiomyoma shows the spindled smooth muscle proliferation intimately associated with vessel walls.
Angioleiomyoma. A collapsed vessel lumen is surrounded by a thickened wall in which the smooth muscle cells continue into the stroma as part of an angioleiomyoma (also known as a vascular leiomyoma). Inflammatory cells are noted.
Leiomyoma. Interlacing fascicles of smooth muscle cells are seen in this leiomyoma. The nuclei are bland.
Leiomyoma. Fascicles of spindled leiomyoma cells show cytoplasmic vacuoles, some adjacent to bland nuclei.
Leiomyoma. The neoplastic cells of leiomyoma show a strong and diffuse cytoplasmic reaction for SMA.
Leiomyoma. The neoplastic cells of leiomyoma show a strong and diffuse cytoplasmic reaction for desmin.

Q: When examining lesions in the Leiomyoma and Angioleiomyoma category, the finding of prominent vascular channels intimately surrounded by proliferating smooth muscle cells specifically identifies an [...].
Angioleiomyoma. Vascular channels are surrounded by a spindle cell proliferation in this nasal cavity angioleiomyoma.
Angioleiomyoma. An angioleiomyoma shows the spindled smooth muscle proliferation intimately associated with vessel walls.
Angioleiomyoma. A collapsed vessel lumen is surrounded by a thickened wall in which the smooth muscle cells continue into the stroma as part of an angioleiomyoma (also known as a vascular leiomyoma). Inflammatory cells are noted.
A: angioleiomyoma
Leiomyoma and Angioleiomyoma
- Clinical: Leiomyomas and angioleiomyomas cause soft tissue swellings and nasal or airway obstruction, with equal sex distribution and an excellent prognosis.
- Micro: Leiomyomas show bland, spindled cells arranged in intersecting fascicles, while angioleiomyomas have a prominent vasculature surrounded by smooth muscle cells.
- Ancillary: Leiomyomas and angioleiomyomas express smooth muscle markers (α-SMA, desmin) but are negative for HMB45, SOX10, and S100.
Reference Gallery:
Sinonasal leiomyoma. CT demonstrating a well-circumscribed mass in the anterior nasal cavity (arrow).
Angioleiomyoma. Vascular channels are surrounded by a spindle cell proliferation in this nasal cavity angioleiomyoma.
Angioleiomyoma. An angioleiomyoma shows the spindled smooth muscle proliferation intimately associated with vessel walls.
Angioleiomyoma. A collapsed vessel lumen is surrounded by a thickened wall in which the smooth muscle cells continue into the stroma as part of an angioleiomyoma (also known as a vascular leiomyoma). Inflammatory cells are noted.
Leiomyoma. Interlacing fascicles of smooth muscle cells are seen in this leiomyoma. The nuclei are bland.
Leiomyoma. Fascicles of spindled leiomyoma cells show cytoplasmic vacuoles, some adjacent to bland nuclei.
Leiomyoma. The neoplastic cells of leiomyoma show a strong and diffuse cytoplasmic reaction for SMA.
Leiomyoma. The neoplastic cells of leiomyoma show a strong and diffuse cytoplasmic reaction for desmin.

Q: Immunohistochemical stains for Leiomyoma and Angioleiomyoma characteristically demonstrate strong and diffuse positivity for the smooth muscle markers [...].
Leiomyoma. The neoplastic cells of leiomyoma show a strong and diffuse cytoplasmic reaction for SMA.
Leiomyoma. The neoplastic cells of leiomyoma show a strong and diffuse cytoplasmic reaction for desmin.
A: SMA and desmin
Leiomyoma and Angioleiomyoma
- Clinical: Leiomyomas and angioleiomyomas cause soft tissue swellings and nasal or airway obstruction, with equal sex distribution and an excellent prognosis.
- Micro: Leiomyomas show bland, spindled cells arranged in intersecting fascicles, while angioleiomyomas have a prominent vasculature surrounded by smooth muscle cells.
- Ancillary: Leiomyomas and angioleiomyomas express smooth muscle markers (α-SMA, desmin) but are negative for HMB45, SOX10, and S100.
Reference Gallery:
Sinonasal leiomyoma. CT demonstrating a well-circumscribed mass in the anterior nasal cavity (arrow).
Angioleiomyoma. Vascular channels are surrounded by a spindle cell proliferation in this nasal cavity angioleiomyoma.
Angioleiomyoma. An angioleiomyoma shows the spindled smooth muscle proliferation intimately associated with vessel walls.
Angioleiomyoma. A collapsed vessel lumen is surrounded by a thickened wall in which the smooth muscle cells continue into the stroma as part of an angioleiomyoma (also known as a vascular leiomyoma). Inflammatory cells are noted.
Leiomyoma. Interlacing fascicles of smooth muscle cells are seen in this leiomyoma. The nuclei are bland.
Leiomyoma. Fascicles of spindled leiomyoma cells show cytoplasmic vacuoles, some adjacent to bland nuclei.
Leiomyoma. The neoplastic cells of leiomyoma show a strong and diffuse cytoplasmic reaction for SMA.
Leiomyoma. The neoplastic cells of leiomyoma show a strong and diffuse cytoplasmic reaction for desmin.

Q: Microscopically, Leiomyosarcoma is characterized by atypical spindle cells arranged in interlacing fascicles, which may exhibit atypical mitotic figures and islands of [...] (a feature not seen in benign smooth muscle tumors).
Leiomyosarcoma. The spindled neoplastic cells show islands of comedonecrosis, a finding not seen in benign smooth muscle tumours.
Leiomyosarcoma. Interlacing fascicles of spindled neoplastic cells are seen with limited pleomorphism.
A: comedonecrosis
Back Extra: Leiomyosarcoma
- Clinical: Symptoms of Leiomyosarcoma (LMS) include a mass lesion, with metastases being rare. Primary head and neck LMSs are very rare, representing 0.01% of all tumours.
- Micro: Leiomyosarcomas are characterized by spindle cells arranged in interlacing fascicles, with atypia, high mitotic activity, and comedonecrosis.
- Ancillary: Immunohistochemical markers such as SMA, desmin, and h-caldesmon are strongly positive in leiomyosarcoma, while RB1 is commonly lost.
Reference Gallery:
Leiomyosarcoma. A left maxillary sinus soft tissue–density mass destroys the surrounding bone and expands into the facial soft tissues.
Leiomyosarcoma. The atypical spindle cell proliferation destroys the bone.
Leiomyosarcoma. The spindled neoplastic cells show islands of comedonecrosis, a finding not seen in benign smooth muscle tumours.
Leiomyosarcoma. The tumour cells scroll off the smooth muscle wall of vessels within the sinonasal tract.
Leiomyosarcoma. The pleomorphic neoplastic tumours cells are noted below an intact respiratory epithelium.
Leiomyosarcoma. The pleomorphic spindled cells infiltrate bone and show atypical mitotic figures.
Leiomyosarcoma. Interlacing fascicles of spindled neoplastic cells are seen with limited pleomorphism.
Leiomyosarcoma. There is a juxtaposition between high-grade tumour cells and low-grade tumour cells (right). It is not uncommon to have variation in grade in the same tumour.
Epithelioid leiomyosarcoma. The epithelioid appearance of leiomyosarcoma can sometimes mimic that of primary squamous cell carcinoma (uninvolved native minor mucoserous glands noted in upper left).
Leiomyosarcoma. The myxoid pattern of leiomyosarcoma demonstrates spindled neoplastic cells suspended in a myxoid to mucinous-type background material.
Leiomyosarcoma. The neoplastic cells of leiomyosarcoma are immunoreactive for desmin.
Leiomyosarcoma. The neoplastic cells of leiomyosarcoma are immunoreactive for SMA.

Q: To confirm the diagnosis of Leiomyosarcoma, immunohistochemical evaluation is characteristically strongly positive for smooth muscle markers such as h-caldesmon, as well as [...].
Leiomyosarcoma. The neoplastic cells of leiomyosarcoma are immunoreactive for desmin.
Leiomyosarcoma. The neoplastic cells of leiomyosarcoma are immunoreactive for SMA.
A: SMA and desmin
Back Extra: Leiomyosarcoma
- Clinical: Symptoms of Leiomyosarcoma (LMS) include a mass lesion, with metastases being rare. Primary head and neck LMSs are very rare, representing 0.01% of all tumours.
- Micro: Leiomyosarcomas are characterized by spindle cells arranged in interlacing fascicles, with atypia, high mitotic activity, and comedonecrosis.
- Ancillary: Immunohistochemical markers such as SMA, desmin, and h-caldesmon are strongly positive in leiomyosarcoma, while RB1 is commonly lost.
Reference Gallery:
Leiomyosarcoma. A left maxillary sinus soft tissue–density mass destroys the surrounding bone and expands into the facial soft tissues.
Leiomyosarcoma. The atypical spindle cell proliferation destroys the bone.
Leiomyosarcoma. The spindled neoplastic cells show islands of comedonecrosis, a finding not seen in benign smooth muscle tumours.
Leiomyosarcoma. The tumour cells scroll off the smooth muscle wall of vessels within the sinonasal tract.
Leiomyosarcoma. The pleomorphic neoplastic tumours cells are noted below an intact respiratory epithelium.
Leiomyosarcoma. The pleomorphic spindled cells infiltrate bone and show atypical mitotic figures.
Leiomyosarcoma. Interlacing fascicles of spindled neoplastic cells are seen with limited pleomorphism.
Leiomyosarcoma. There is a juxtaposition between high-grade tumour cells and low-grade tumour cells (right). It is not uncommon to have variation in grade in the same tumour.
Epithelioid leiomyosarcoma. The epithelioid appearance of leiomyosarcoma can sometimes mimic that of primary squamous cell carcinoma (uninvolved native minor mucoserous glands noted in upper left).
Leiomyosarcoma. The myxoid pattern of leiomyosarcoma demonstrates spindled neoplastic cells suspended in a myxoid to mucinous-type background material.
Leiomyosarcoma. The neoplastic cells of leiomyosarcoma are immunoreactive for desmin.
Leiomyosarcoma. The neoplastic cells of leiomyosarcoma are immunoreactive for SMA.

Q: The [...] variant of Leiomyosarcoma is characterized by rounder neoplastic cells rather than classic spindle cells, which can sometimes morphologically mimic a primary squamous cell carcinoma.
Epithelioid leiomyosarcoma. The epithelioid appearance of leiomyosarcoma can sometimes mimic that of primary squamous cell carcinoma (uninvolved native minor mucoserous glands noted in upper left).
A: epithelioid
Back Extra: Leiomyosarcoma
- Clinical: Symptoms of Leiomyosarcoma (LMS) include a mass lesion, with metastases being rare. Primary head and neck LMSs are very rare, representing 0.01% of all tumours.
- Micro: Leiomyosarcomas are characterized by spindle cells arranged in interlacing fascicles, with atypia, high mitotic activity, and comedonecrosis.
- Ancillary: Immunohistochemical markers such as SMA, desmin, and h-caldesmon are strongly positive in leiomyosarcoma, while RB1 is commonly lost.
Reference Gallery:
Leiomyosarcoma. A left maxillary sinus soft tissue–density mass destroys the surrounding bone and expands into the facial soft tissues.
Leiomyosarcoma. The atypical spindle cell proliferation destroys the bone.
Leiomyosarcoma. The spindled neoplastic cells show islands of comedonecrosis, a finding not seen in benign smooth muscle tumours.
Leiomyosarcoma. The tumour cells scroll off the smooth muscle wall of vessels within the sinonasal tract.
Leiomyosarcoma. The pleomorphic neoplastic tumours cells are noted below an intact respiratory epithelium.
Leiomyosarcoma. The pleomorphic spindled cells infiltrate bone and show atypical mitotic figures.
Leiomyosarcoma. Interlacing fascicles of spindled neoplastic cells are seen with limited pleomorphism.
Leiomyosarcoma. There is a juxtaposition between high-grade tumour cells and low-grade tumour cells (right). It is not uncommon to have variation in grade in the same tumour.
Epithelioid leiomyosarcoma. The epithelioid appearance of leiomyosarcoma can sometimes mimic that of primary squamous cell carcinoma (uninvolved native minor mucoserous glands noted in upper left).
Leiomyosarcoma. The myxoid pattern of leiomyosarcoma demonstrates spindled neoplastic cells suspended in a myxoid to mucinous-type background material.
Leiomyosarcoma. The neoplastic cells of leiomyosarcoma are immunoreactive for desmin.
Leiomyosarcoma. The neoplastic cells of leiomyosarcoma are immunoreactive for SMA.

Q: Histologically, [...] presents with interlacing fascicles of spindle cells showing blunt-ended (cigar-shaped) nuclei and ample eosinophilic cytoplasm. While mild to moderate pleomorphism may be present, there is no tumor necrosis and the mitotic count remains strictly ≤ 4 mitoses/2 mm².
Smooth muscle tumour of uncertain malignant potential. Fascicles appear less organized and are composed of spindle cells with mild to moderate to focally marked nuclear pleomorphism, hyperchromatic nuclei, and eosinophilic cytoplasm. Despite these atypical nuclear features, mitotic figures and tumour necrosis are not present. The marked cellularity and nuclear pleomorphism are not focal but include extensive areas of the neoplasm and were therefore beyond those that might be ascribed to findings seen in symplastic leiomyomas.
Smooth muscle tumour of uncertain malignant potential. Two mitotic figures (at 3 o’clock and at 9 o’clock) are seen, but overall the mitotic count was ≤ 4 mitoses/2 mm², with no tumour necrosis.
A: Smooth Muscle Tumour of Uncertain Malignant Potential
Back Extra: Smooth Muscle Tumour of Uncertain Malignant Potential
- Clinical: Patients with Smooth Muscle Tumour of Uncertain Malignant Potential (STUMP) are aged 20–44 years, with both sexes affected. Sinonasal tumours present with nasal obstruction and facial pain.
- Micro: STUMPs form interlacing fascicles and bundles of smooth muscle cells with blunt-ended nuclei and ample eosinophilic cytoplasm, showing slightly increased cellularity, mild to moderate pleomorphism, and a mitotic count of ≤ 4 mitoses/2 mm².
- Ancillary: Immunocytochemistry is positive for SMA, MSA, and desmin, with no nuclear expression of β-catenin, HMB45, SOX10, S100, or keratins.
Reference Gallery:
Smooth muscle tumour of uncertain malignant potential. A submucosal cellular neoplasm composed of spindle-shaped cells with deeply eosinophilic cytoplasm, characterized by interlacing and/or intersecting fascicles or bundles, some at acute angles.
Smooth muscle tumour of uncertain malignant potential. Areas of the tumour showing features of benign smooth muscle tumour (i.e. leiomyoma) including well-organized fascicles composed of spindle-shaped cells with uniform-appearing nuclei, some with blunt ends (cigar-shaped nuclei), and abundant eosinophilic cytoplasm.
Smooth muscle tumour of uncertain malignant potential. Fascicles appear less organized and are composed of spindle cells with mild to moderate to focally marked nuclear pleomorphism, hyperchromatic nuclei, and eosinophilic cytoplasm. Despite these atypical nuclear features, mitotic figures and tumour necrosis are not present. The marked cellularity and nuclear pleomorphism are not focal but include extensive areas of the neoplasm and were therefore beyond those that might be ascribed to findings seen in symplastic leiomyomas.
Smooth muscle tumour of uncertain malignant potential. High-magnification view shows an admixture of cells including more-differentiated cells characterized by uniform nuclei with blunt ends (cigar-shaped nuclei) and evenly dispersed nuclear chromatin admixed with less differentiated cells characterized by nuclear hyperchromasia and moderate to marked nuclear pleomorphism. All cells have brightly eosinophilic-appearing cytoplasm. Mitoses and tumour necrosis were not identified.
Smooth muscle tumour of uncertain malignant potential. Two mitotic figures (at 3 o’clock and at 9 o’clock) are seen, but overall the mitotic count was ≤ 4 mitoses/2 mm², with no tumour necrosis.
Smooth muscle tumour of uncertain malignant potential. The neoplastic cells are diffusely immunoreactive for SMMHC.
Smooth muscle tumour of uncertain malignant potential. The neoplastic cells are diffusely immunoreactive for caldesmon.
Smooth muscle tumour of uncertain malignant potential. The neoplastic cells are diffusely immunoreactive for desmin.
Smooth muscle tumour of uncertain malignant potential. Ki-67/CD45 double staining shows a varying proliferation index, at < 5% in the better-differentiated areas of the neoplasm (right) to > 30% in the less-differentiated areas (left) (brown chromogen for Ki-67; red chromogen for CD45).

Q: Immunohistochemical staining in [...] demonstrates diffuse positivity for smooth muscle markers such as SMMHC, caldesmon, and desmin, while lacking expression of HMB45, SOX10, or S100.
Smooth muscle tumour of uncertain malignant potential. The neoplastic cells are diffusely immunoreactive for SMMHC.
Smooth muscle tumour of uncertain malignant potential. The neoplastic cells are diffusely immunoreactive for caldesmon.
Smooth muscle tumour of uncertain malignant potential. The neoplastic cells are diffusely immunoreactive for desmin.
A: Smooth Muscle Tumour of Uncertain Malignant Potential
Back Extra: Smooth Muscle Tumour of Uncertain Malignant Potential
- Clinical: Patients with Smooth Muscle Tumour of Uncertain Malignant Potential (STUMP) are aged 20–44 years, with both sexes affected. Sinonasal tumours present with nasal obstruction and facial pain.
- Micro: STUMPs form interlacing fascicles and bundles of smooth muscle cells with blunt-ended nuclei and ample eosinophilic cytoplasm, showing slightly increased cellularity, mild to moderate pleomorphism, and a mitotic count of ≤ 4 mitoses/2 mm².
- Ancillary: Immunocytochemistry is positive for SMA, MSA, and desmin, with no nuclear expression of β-catenin, HMB45, SOX10, S100, or keratins.
Reference Gallery:
Smooth muscle tumour of uncertain malignant potential. A submucosal cellular neoplasm composed of spindle-shaped cells with deeply eosinophilic cytoplasm, characterized by interlacing and/or intersecting fascicles or bundles, some at acute angles.
Smooth muscle tumour of uncertain malignant potential. Areas of the tumour showing features of benign smooth muscle tumour (i.e. leiomyoma) including well-organized fascicles composed of spindle-shaped cells with uniform-appearing nuclei, some with blunt ends (cigar-shaped nuclei), and abundant eosinophilic cytoplasm.
Smooth muscle tumour of uncertain malignant potential. Fascicles appear less organized and are composed of spindle cells with mild to moderate to focally marked nuclear pleomorphism, hyperchromatic nuclei, and eosinophilic cytoplasm. Despite these atypical nuclear features, mitotic figures and tumour necrosis are not present. The marked cellularity and nuclear pleomorphism are not focal but include extensive areas of the neoplasm and were therefore beyond those that might be ascribed to findings seen in symplastic leiomyomas.
Smooth muscle tumour of uncertain malignant potential. High-magnification view shows an admixture of cells including more-differentiated cells characterized by uniform nuclei with blunt ends (cigar-shaped nuclei) and evenly dispersed nuclear chromatin admixed with less differentiated cells characterized by nuclear hyperchromasia and moderate to marked nuclear pleomorphism. All cells have brightly eosinophilic-appearing cytoplasm. Mitoses and tumour necrosis were not identified.
Smooth muscle tumour of uncertain malignant potential. Two mitotic figures (at 3 o’clock and at 9 o’clock) are seen, but overall the mitotic count was ≤ 4 mitoses/2 mm², with no tumour necrosis.
Smooth muscle tumour of uncertain malignant potential. The neoplastic cells are diffusely immunoreactive for SMMHC.
Smooth muscle tumour of uncertain malignant potential. The neoplastic cells are diffusely immunoreactive for caldesmon.
Smooth muscle tumour of uncertain malignant potential. The neoplastic cells are diffusely immunoreactive for desmin.
Smooth muscle tumour of uncertain malignant potential. Ki-67/CD45 double staining shows a varying proliferation index, at < 5% in the better-differentiated areas of the neoplasm (right) to > 30% in the less-differentiated areas (left) (brown chromogen for Ki-67; red chromogen for CD45).

Q: Microscopically, [...] is a soft tissue tumor characterized by hypocellular lobules, fibrous septa, and cells forming cords and complex trabecular arrays within an abundant pale-blue myxoid matrix.
Extraskeletal myxoid chondrosarcoma. The tumour shows a multinodular appearance with fibrous septa forming hypocellular lobules with abundant pale-blue chondromyxoid matrix.
Extraskeletal myxoid chondrosarcoma. The tumour cells form cords, small clusters, and complex trabecular and cribriform arrays.
Extraskeletal myxoid chondrosarcoma. The basaloid cords of neoplastic cells are set within a myxoid background, with fibrous septa noted.
A: Extraskeletal Myxoid Chondrosarcoma
Back Extra: Extraskeletal Myxoid Chondrosarcoma
- Clinical: Patients may present with an enlarging deep-seated soft tissue mass, often associated with pain, diplopia, or headache.
- Micro: The tumour is multinodular with fibrous septa separating hypocellular lobules, and an abundant pale-blue myxoid matrix. Cells form cords, clusters, and complex trabecular arrays.
- Ancillary: NR4A3 gene rearrangement is a hallmark of extraskeletal myxoid chondrosarcoma, often involving EWSR1 or TAF15 fusions.
Reference Gallery:
Extraskeletal myxoid chondrosarcoma. A gross photograph demonstrates a multinodular appearance with a myxoid, pale-tan to white appearance.
Extraskeletal myxoid chondrosarcoma. The tumour shows a multinodular appearance with fibrous septa forming hypocellular lobules with abundant pale-blue chondromyxoid matrix.
Extraskeletal myxoid chondrosarcoma. The tumour cells form cords, small clusters, and complex trabecular and cribriform arrays.
Extraskeletal myxoid chondrosarcoma. The basaloid cords of neoplastic cells are set within a myxoid background, with fibrous septa noted.
Extraskeletal myxoid chondrosarcoma. This EWSR1 break-apart probe demonstrates that EWSR1 is involved, but it does not confirm the partner.

Q: The hallmark molecular finding in Extraskeletal Myxoid Chondrosarcoma is a gene rearrangement involving [...], which most commonly fuses with EWSR1 or TAF15.
Extraskeletal myxoid chondrosarcoma. This EWSR1 break-apart probe demonstrates that EWSR1 is involved, but it does not confirm the partner.
A: NR4A3
Back Extra: Extraskeletal Myxoid Chondrosarcoma
- Clinical: Patients may present with an enlarging deep-seated soft tissue mass, often associated with pain, diplopia, or headache.
- Micro: The tumour is multinodular with fibrous septa separating hypocellular lobules, and an abundant pale-blue myxoid matrix. Cells form cords, clusters, and complex trabecular arrays.
- Ancillary: NR4A3 gene rearrangement is a hallmark of extraskeletal myxoid chondrosarcoma, often involving EWSR1 or TAF15 fusions.
Reference Gallery:
Extraskeletal myxoid chondrosarcoma. A gross photograph demonstrates a multinodular appearance with a myxoid, pale-tan to white appearance.
Extraskeletal myxoid chondrosarcoma. The tumour shows a multinodular appearance with fibrous septa forming hypocellular lobules with abundant pale-blue chondromyxoid matrix.
Extraskeletal myxoid chondrosarcoma. The tumour cells form cords, small clusters, and complex trabecular and cribriform arrays.
Extraskeletal myxoid chondrosarcoma. The basaloid cords of neoplastic cells are set within a myxoid background, with fibrous septa noted.
Extraskeletal myxoid chondrosarcoma. This EWSR1 break-apart probe demonstrates that EWSR1 is involved, but it does not confirm the partner.

Q: Microscopically, [...] is characterized by sheets and nests of epithelioid to ovoid cells with monomorphic nuclei and a prominent capillary-sized vasculature.
GLI1-altered soft tissue tumour, with ACTB::GLI1 fusion gene. Sheets of epithelioid to ovoid cells with monomorphic nuclei. Extension into vascular spaces is common.
GLI1-altered soft tissue tumour, with ACTB::GLI1 fusion gene. The nuclei are round to ovoid and relatively monomorphic, with small nucleoli. A prominent capillary-sized vasculature permeates the tumour.
A: GLI1-altered soft tissue tumor
Back Extra: GLI1-altered soft tissue tumour
- Clinical: GLI1-altered soft tissue tumours typically present as a slow-growing, painless mass, most commonly in young adults, with no overt sex predilection.
- Micro: These tumours are characterized by sheets and nests of epithelioid to ovoid cells with monomorphic nuclei and a prominent capillary-sized vasculature.
- Ancillary: The diagnosis is confirmed by the presence of a GLI1 rearrangement or amplification, with variable immunoreactivity for S100, CD10, and EMA.
Reference Gallery:
GLI1-altered soft tissue tumour, with ACTB::GLI1 fusion gene. Sheets of epithelioid to ovoid cells with monomorphic nuclei. Extension into vascular spaces is common.
GLI1-altered soft tissue tumour, with ACTB::GLI1 fusion gene. The nuclei are round to ovoid and relatively monomorphic, with small nucleoli. A prominent capillary-sized vasculature permeates the tumour.
GLI1-altered soft tissue tumour with MALAT1::GLI1 fusion gene. Infiltrative margins are present in some cases.
GLI1-altered soft tissue tumour with MALAT1::GLI1 fusion gene. Variable immunoreactivity for S100 may be present.
GLI1-altered soft tissue tumour with GLI1 amplification. Amplification of GLI1 may be associated with amplification of adjacent genes, including STAT6, which can be demonstrated immunohistochemically.

Q: In cases of GLI1-altered soft tissue tumor driven by gene amplification, there may be co-amplification of adjacent genes, leading to characteristic immunohistochemical expression of [...].
GLI1-altered soft tissue tumour with GLI1 amplification. Amplification of GLI1 may be associated with amplification of adjacent genes, including STAT6, which can be demonstrated immunohistochemically.
A: STAT6
Back Extra: GLI1-altered soft tissue tumour
- Clinical: GLI1-altered soft tissue tumours typically present as a slow-growing, painless mass, most commonly in young adults, with no overt sex predilection.
- Micro: These tumours are characterized by sheets and nests of epithelioid to ovoid cells with monomorphic nuclei and a prominent capillary-sized vasculature.
- Ancillary: The diagnosis is confirmed by the presence of a GLI1 rearrangement or amplification, with variable immunoreactivity for S100, CD10, and EMA.
Reference Gallery:
GLI1-altered soft tissue tumour, with ACTB::GLI1 fusion gene. Sheets of epithelioid to ovoid cells with monomorphic nuclei. Extension into vascular spaces is common.
GLI1-altered soft tissue tumour, with ACTB::GLI1 fusion gene. The nuclei are round to ovoid and relatively monomorphic, with small nucleoli. A prominent capillary-sized vasculature permeates the tumour.
GLI1-altered soft tissue tumour with MALAT1::GLI1 fusion gene. Infiltrative margins are present in some cases.
GLI1-altered soft tissue tumour with MALAT1::GLI1 fusion gene. Variable immunoreactivity for S100 may be present.
GLI1-altered soft tissue tumour with GLI1 amplification. Amplification of GLI1 may be associated with amplification of adjacent genes, including STAT6, which can be demonstrated immunohistochemically.

Q: A GLI1-altered soft tissue tumor may show variable immunoreactivity for CD10, EMA, and [...].
GLI1-altered soft tissue tumour with MALAT1::GLI1 fusion gene. Variable immunoreactivity for S100 may be present.
A: S100
Back Extra: GLI1-altered soft tissue tumour
- Clinical: GLI1-altered soft tissue tumours typically present as a slow-growing, painless mass, most commonly in young adults, with no overt sex predilection.
- Micro: These tumours are characterized by sheets and nests of epithelioid to ovoid cells with monomorphic nuclei and a prominent capillary-sized vasculature.
- Ancillary: The diagnosis is confirmed by the presence of a GLI1 rearrangement or amplification, with variable immunoreactivity for S100, CD10, and EMA.
Reference Gallery:
GLI1-altered soft tissue tumour, with ACTB::GLI1 fusion gene. Sheets of epithelioid to ovoid cells with monomorphic nuclei. Extension into vascular spaces is common.
GLI1-altered soft tissue tumour, with ACTB::GLI1 fusion gene. The nuclei are round to ovoid and relatively monomorphic, with small nucleoli. A prominent capillary-sized vasculature permeates the tumour.
GLI1-altered soft tissue tumour with MALAT1::GLI1 fusion gene. Infiltrative margins are present in some cases.
GLI1-altered soft tissue tumour with MALAT1::GLI1 fusion gene. Variable immunoreactivity for S100 may be present.
GLI1-altered soft tissue tumour with GLI1 amplification. Amplification of GLI1 may be associated with amplification of adjacent genes, including STAT6, which can be demonstrated immunohistochemically.

Q: Microscopically, a Myxoma typically features a loose, hypocellular proliferation of spindled to stellate cells embedded in a prominent [...] stroma, often with fine collagen bands.
Sinonasal tract myxoma. There is a loose, hypocellular stroma with spindled to stellate cells within a myxoid matrix.
Sinonasal tract myxoma. A collagenous and myxoid stroma is the predominant finding, with only isolated, bland spindled neoplastic cells.
A: myxoid
Back Extra: Myxoma
- Clinical: Myxoma typically presents as a slow-growing, site-specific swelling with symptoms related to local tumor extension into adjacent structures (e.g., middle ear, palate, orbit, nasal cavity).
- Micro: Myxomas are characterized by a loose hypocellular proliferation of spindled, stellate, or round cells within a myxoid stroma, often containing arciform thin blood vessels and scattered fine collagen bands.
- Ancillary: Immunohistochemistry may show variable SMA and nuclear β-catenin reactivity. Nuclear β-catenin staining is useful in selected cases, particularly in patients with Carney complex.
Reference Gallery:
Sinonasal tract myxoma. There is a loose, hypocellular stroma with spindled to stellate cells within a myxoid matrix.
Sinonasal tract myxoma. A collagenous and myxoid stroma is the predominant finding, with only isolated, bland spindled neoplastic cells.
External ear canal myxoma. Note the myxoid stroma and polypoid appearance.
External ear canal myxoma in a patient with Carney complex. Overlying epithelium shows basaloid extensions, which may mimic superficial basal cell carcinoma. Such epithelial basaloid buds may be seen in lesions of the external auditory canal in patients with Carney complex.

Q: In a patient with Myxoma of the external ear canal, the presence of overlying epithelial basaloid buds or extensions is a classic finding associated with [...].
External ear canal myxoma. Note the myxoid stroma and polypoid appearance.
External ear canal myxoma in a patient with Carney complex. Overlying epithelium shows basaloid extensions, which may mimic superficial basal cell carcinoma. Such epithelial basaloid buds may be seen in lesions of the external auditory canal in patients with Carney complex.
A: Carney complex
Back Extra: Myxoma
- Clinical: Myxoma typically presents as a slow-growing, site-specific swelling with symptoms related to local tumor extension into adjacent structures (e.g., middle ear, palate, orbit, nasal cavity).
- Micro: Myxomas are characterized by a loose hypocellular proliferation of spindled, stellate, or round cells within a myxoid stroma, often containing arciform thin blood vessels and scattered fine collagen bands.
- Ancillary: Immunohistochemistry may show variable SMA and nuclear β-catenin reactivity. Nuclear β-catenin staining is useful in selected cases, particularly in patients with Carney complex.
Reference Gallery:
Sinonasal tract myxoma. There is a loose, hypocellular stroma with spindled to stellate cells within a myxoid matrix.
Sinonasal tract myxoma. A collagenous and myxoid stroma is the predominant finding, with only isolated, bland spindled neoplastic cells.
External ear canal myxoma. Note the myxoid stroma and polypoid appearance.
External ear canal myxoma in a patient with Carney complex. Overlying epithelium shows basaloid extensions, which may mimic superficial basal cell carcinoma. Such epithelial basaloid buds may be seen in lesions of the external auditory canal in patients with Carney complex.

Q: The characteristic microscopic appearance of a phosphaturic mesenchymal tumor consists of bland spindle cells within a basophilic, smudgy matrix containing typical [...].
Phosphaturic mesenchymal tumour. Spindle cell neoplastic proliferation with grungy stromal calcification.
Phosphaturic mesenchymal tumour. Basophilic, smudgy stroma with grungy calcification (right) and a paucicellular, bland spindle cell proliferation along with dilated thin blood vessels (left).
Phosphaturic mesenchymal tumour. The tumour is composed of a haphazard, patternless proliferation of spindle cells with slender tapering nuclei. Typical basophilic, smudgy matrix and flocculent calcification are also present.
A: grungy calcification
Q: Phosphaturic Mesenchymal Tumour
- Clinical: Most patients with phosphaturic mesenchymal tumours present with muscle weakness, fatigue, bone pain, and fractures due to [...].
- Micro: The characteristic microscopic features of phosphaturic mesenchymal tumours include [...] in a richly vascularized stroma with basophilic, smudgy matrix and grungy calcification.
- Ancillary: Diagnosis is confirmed by chromogenic in situ hybridization for [...] and identification of FN1::FGFR1 or FN1::FGF1 fusions.
Reference Gallery:
Phosphaturic mesenchymal tumour. Contrast-enhanced CT shows an intensely enhancing alveolar soft tissue mass involving the anterior and medial maxillary wall.
Phosphaturic mesenchymal tumour. Spindle cell neoplastic proliferation with grungy stromal calcification.
Phosphaturic mesenchymal tumour. Basophilic, smudgy stroma with grungy calcification (right) and a paucicellular, bland spindle cell proliferation along with dilated thin blood vessels (left).
Phosphaturic mesenchymal tumour. The tumour is composed of a haphazard, patternless proliferation of spindle cells with slender tapering nuclei. Typical basophilic, smudgy matrix and flocculent calcification are also present.
Phosphaturic mesenchymal tumour. Thick blood vessels and mature adipose tissue are common among tumours in the head and neck.
Phosphaturic mesenchymal tumour. Osteoclastic giant cells may be prominent in some tumours.
Phosphaturic mesenchymal tumour. Tumours composed of spindle cells with a myoid appearance and scant stroma may be seen in the head and neck region.
Phosphaturic mesenchymal tumour. Tumours may harbour aneurysmal bone cyst–like areas.
Phosphaturic mesenchymal tumour. Chromogenic in situ hybridization shows FGF23 mRNA in the tumour cells.
A: tumour-induced osteomalacia; bland spindle to stellate cells; FGF23 mRNA

Q: The diagnosis of a phosphaturic mesenchymal tumor is frequently confirmed by performing chromogenic in situ hybridization (CISH) to detect the presence of [...].
Phosphaturic mesenchymal tumour. Chromogenic in situ hybridization shows FGF23 mRNA in the tumour cells.
A: FGF23 mRNA
Q: Phosphaturic Mesenchymal Tumour
- Clinical: Most patients with phosphaturic mesenchymal tumours present with muscle weakness, fatigue, bone pain, and fractures due to [...].
- Micro: The characteristic microscopic features of phosphaturic mesenchymal tumours include [...] in a richly vascularized stroma with basophilic, smudgy matrix and grungy calcification.
- Ancillary: Diagnosis is confirmed by chromogenic in situ hybridization for [...] and identification of FN1::FGFR1 or FN1::FGF1 fusions.
Reference Gallery:
Phosphaturic mesenchymal tumour. Contrast-enhanced CT shows an intensely enhancing alveolar soft tissue mass involving the anterior and medial maxillary wall.
Phosphaturic mesenchymal tumour. Spindle cell neoplastic proliferation with grungy stromal calcification.
Phosphaturic mesenchymal tumour. Basophilic, smudgy stroma with grungy calcification (right) and a paucicellular, bland spindle cell proliferation along with dilated thin blood vessels (left).
Phosphaturic mesenchymal tumour. The tumour is composed of a haphazard, patternless proliferation of spindle cells with slender tapering nuclei. Typical basophilic, smudgy matrix and flocculent calcification are also present.
Phosphaturic mesenchymal tumour. Thick blood vessels and mature adipose tissue are common among tumours in the head and neck.
Phosphaturic mesenchymal tumour. Osteoclastic giant cells may be prominent in some tumours.
Phosphaturic mesenchymal tumour. Tumours composed of spindle cells with a myoid appearance and scant stroma may be seen in the head and neck region.
Phosphaturic mesenchymal tumour. Tumours may harbour aneurysmal bone cyst–like areas.
Phosphaturic mesenchymal tumour. Chromogenic in situ hybridization shows FGF23 mRNA in the tumour cells.
A: tumour-induced osteomalacia; bland spindle to stellate cells; FGF23 mRNA

Q: Microscopically, classic cases of Synovial Sarcoma exhibit a [...] appearance, characterized by streaming fascicles of spindle cells intermixed with distinct gland formation and dystrophic calcifications.
Synovial sarcoma. A biphasic appearance is noted, with streaming fascicles of neoplastic cells associated with gland formation. Dystrophic calcifications are present.
Synovial sarcoma. Elongated patulous vessels are noted in this tumour, where there are alternating fascicles of spindled cells with epithelioid cells. Calcifications are present.
A: biphasic
Back Extra: Synovial Sarcoma
- Clinical: Synovial Sarcoma typically presents as a deep-seated, palpable swelling in patients under 50 years of age, often with pain or tenderness.
- Micro: Synovial Sarcoma can exhibit a biphasic appearance with streaming fascicles of spindle cells and gland formation, along with dystrophic calcifications.
- Ancillary: TLE1 nuclear immunoreactivity is present in up to 95% of Synovial Sarcoma cases, and the SS18::SSX fusion gene is a key molecular marker for diagnosis.
Reference Gallery:
Synovial sarcoma. An axial CT image shows displacement of the trachea by a large, destructive soft tissue–density mass in the low anterior neck.
Synovial sarcoma. This gross illustration demonstrates numerous cysts and spaces, characteristic of a biphasic tumour.
Synovial sarcoma. A biphasic appearance is noted, with streaming fascicles of neoplastic cells associated with gland formation. Dystrophic calcifications are present.
Synovial sarcoma. Elongated patulous vessels are noted in this tumour, where there are alternating fascicles of spindled cells with epithelioid cells. Calcifications are present.
Synovial sarcoma. A spindled population is present, but there is a subtle epithelioid quality to it, which can be highlighted with cytokeratin.
Synovial sarcoma. The epithelioid cells are highlighted by a strong pancytokeratin immunoreaction.
Synovial sarcoma. A poorly differentiated tumour exhibits more pleomorphism within a spindled cell population.
Synovial sarcoma. All of the neoplastic cells show a strong and diffuse nuclear reaction for TLE1 by immunohistochemistry.

Q: In Synovial Sarcoma, up to 95% of cases exhibit strong and diffuse nuclear immunoreactivity for the marker [...], which is associated with the characteristic SS18::SSX fusion gene.
Synovial sarcoma. All of the neoplastic cells show a strong and diffuse nuclear reaction for TLE1 by immunohistochemistry.
A: TLE1
Back Extra: Synovial Sarcoma
- Clinical: Synovial Sarcoma typically presents as a deep-seated, palpable swelling in patients under 50 years of age, often with pain or tenderness.
- Micro: Synovial Sarcoma can exhibit a biphasic appearance with streaming fascicles of spindle cells and gland formation, along with dystrophic calcifications.
- Ancillary: TLE1 nuclear immunoreactivity is present in up to 95% of Synovial Sarcoma cases, and the SS18::SSX fusion gene is a key molecular marker for diagnosis.
Reference Gallery:
Synovial sarcoma. An axial CT image shows displacement of the trachea by a large, destructive soft tissue–density mass in the low anterior neck.
Synovial sarcoma. This gross illustration demonstrates numerous cysts and spaces, characteristic of a biphasic tumour.
Synovial sarcoma. A biphasic appearance is noted, with streaming fascicles of neoplastic cells associated with gland formation. Dystrophic calcifications are present.
Synovial sarcoma. Elongated patulous vessels are noted in this tumour, where there are alternating fascicles of spindled cells with epithelioid cells. Calcifications are present.
Synovial sarcoma. A spindled population is present, but there is a subtle epithelioid quality to it, which can be highlighted with cytokeratin.
Synovial sarcoma. The epithelioid cells are highlighted by a strong pancytokeratin immunoreaction.
Synovial sarcoma. A poorly differentiated tumour exhibits more pleomorphism within a spindled cell population.
Synovial sarcoma. All of the neoplastic cells show a strong and diffuse nuclear reaction for TLE1 by immunohistochemistry.

Q: In Synovial Sarcoma, the distinct epithelioid cell population can be strongly highlighted using a [...] immunostain, differentiating it from the surrounding spindle cell component.
Synovial sarcoma. A spindled population is present, but there is a subtle epithelioid quality to it, which can be highlighted with cytokeratin.
Synovial sarcoma. The epithelioid cells are highlighted by a strong pancytokeratin immunoreaction.
A: pancytokeratin
Back Extra: Synovial Sarcoma
- Clinical: Synovial Sarcoma typically presents as a deep-seated, palpable swelling in patients under 50 years of age, often with pain or tenderness.
- Micro: Synovial Sarcoma can exhibit a biphasic appearance with streaming fascicles of spindle cells and gland formation, along with dystrophic calcifications.
- Ancillary: TLE1 nuclear immunoreactivity is present in up to 95% of Synovial Sarcoma cases, and the SS18::SSX fusion gene is a key molecular marker for diagnosis.
Reference Gallery:
Synovial sarcoma. An axial CT image shows displacement of the trachea by a large, destructive soft tissue–density mass in the low anterior neck.
Synovial sarcoma. This gross illustration demonstrates numerous cysts and spaces, characteristic of a biphasic tumour.
Synovial sarcoma. A biphasic appearance is noted, with streaming fascicles of neoplastic cells associated with gland formation. Dystrophic calcifications are present.
Synovial sarcoma. Elongated patulous vessels are noted in this tumour, where there are alternating fascicles of spindled cells with epithelioid cells. Calcifications are present.
Synovial sarcoma. A spindled population is present, but there is a subtle epithelioid quality to it, which can be highlighted with cytokeratin.
Synovial sarcoma. The epithelioid cells are highlighted by a strong pancytokeratin immunoreaction.
Synovial sarcoma. A poorly differentiated tumour exhibits more pleomorphism within a spindled cell population.
Synovial sarcoma. All of the neoplastic cells show a strong and diffuse nuclear reaction for TLE1 by immunohistochemistry.

Q: Immunohistochemical evaluation of Ewing Sarcoma classically demonstrates strong, diffuse [...] positivity for CD99.
Ewing sarcoma. Sheets and nests of uniform small round cells with a moderate amount of eosinophilic cytoplasm and oval nuclei with delicate chromatin.
Ewing sarcoma. Diffuse membranous CD99 positivity.
A: membranous
Back Extra: Ewing Sarcoma
- Clinical: Patients with Ewing sarcoma often present with a palpable mass or mass effect, including pain, swelling, bleeding, or pathological fracture.
- Micro: Ewing sarcoma is characterized by hypercellular sheets and nests of uniform small round cells with a scant amount of eosinophilic to clear cytoplasm and occasional rosette formation.
- Ancillary: IHC shows consistent membranous positivity for CD99 and nuclear positivity for NKX2-2. Genetic confirmation is recommended, with about 85–90% of cases showing t(11;22)(q24;q12), resulting in EWSR1::FLI1 fusion.
Reference Gallery:
Ewing sarcoma. Sheets and nests of uniform small round cells with a moderate amount of eosinophilic cytoplasm and oval nuclei with delicate chromatin.
Ewing sarcoma. Diffuse membranous CD99 positivity.
Ewing sarcoma. Break-apart FISH shows a split in the red and green signals, confirming the presence of EWSR1 rearrangement.
Adamantinoma-like Ewing sarcoma. Nested and lobulated architecture with peripheral palisading and hyalinized stroma.
Adamantinoma-like Ewing sarcoma. Focal formation of compact keratin pearls.
Adamantinoma-like Ewing sarcoma. Diffuse cytokeratin AE1/AE3 positivity.
Adamantinoma-like Ewing sarcoma. Diffuse p40 positivity.

Q: Approximately 85–90% of Ewing Sarcoma cases are driven by the [...] translocation, resulting in an EWSR1::FLI1 fusion.
Ewing sarcoma. Break-apart FISH shows a split in the red and green signals, confirming the presence of EWSR1 rearrangement.
A: t(11;22)(q24;q12)
Back Extra: Ewing Sarcoma
- Clinical: Patients with Ewing sarcoma often present with a palpable mass or mass effect, including pain, swelling, bleeding, or pathological fracture.
- Micro: Ewing sarcoma is characterized by hypercellular sheets and nests of uniform small round cells with a scant amount of eosinophilic to clear cytoplasm and occasional rosette formation.
- Ancillary: IHC shows consistent membranous positivity for CD99 and nuclear positivity for NKX2-2. Genetic confirmation is recommended, with about 85–90% of cases showing t(11;22)(q24;q12), resulting in EWSR1::FLI1 fusion.
Reference Gallery:
Ewing sarcoma. Sheets and nests of uniform small round cells with a moderate amount of eosinophilic cytoplasm and oval nuclei with delicate chromatin.
Ewing sarcoma. Diffuse membranous CD99 positivity.
Ewing sarcoma. Break-apart FISH shows a split in the red and green signals, confirming the presence of EWSR1 rearrangement.
Adamantinoma-like Ewing sarcoma. Nested and lobulated architecture with peripheral palisading and hyalinized stroma.
Adamantinoma-like Ewing sarcoma. Focal formation of compact keratin pearls.
Adamantinoma-like Ewing sarcoma. Diffuse cytokeratin AE1/AE3 positivity.
Adamantinoma-like Ewing sarcoma. Diffuse p40 positivity.

Q: The [...] variant of Ewing Sarcoma displays complex epithelial differentiation, morphologically showing compact keratin pearls and immunohistochemically expressing pan-cytokeratin and p40.
Adamantinoma-like Ewing sarcoma. Nested and lobulated architecture with peripheral palisading and hyalinized stroma.
Adamantinoma-like Ewing sarcoma. Focal formation of compact keratin pearls.
Adamantinoma-like Ewing sarcoma. Diffuse p40 positivity.
A: adamantinoma-like
Back Extra: Ewing Sarcoma
- Clinical: Patients with Ewing sarcoma often present with a palpable mass or mass effect, including pain, swelling, bleeding, or pathological fracture.
- Micro: Ewing sarcoma is characterized by hypercellular sheets and nests of uniform small round cells with a scant amount of eosinophilic to clear cytoplasm and occasional rosette formation.
- Ancillary: IHC shows consistent membranous positivity for CD99 and nuclear positivity for NKX2-2. Genetic confirmation is recommended, with about 85–90% of cases showing t(11;22)(q24;q12), resulting in EWSR1::FLI1 fusion.
Reference Gallery:
Ewing sarcoma. Sheets and nests of uniform small round cells with a moderate amount of eosinophilic cytoplasm and oval nuclei with delicate chromatin.
Ewing sarcoma. Diffuse membranous CD99 positivity.
Ewing sarcoma. Break-apart FISH shows a split in the red and green signals, confirming the presence of EWSR1 rearrangement.
Adamantinoma-like Ewing sarcoma. Nested and lobulated architecture with peripheral palisading and hyalinized stroma.
Adamantinoma-like Ewing sarcoma. Focal formation of compact keratin pearls.
Adamantinoma-like Ewing sarcoma. Diffuse cytokeratin AE1/AE3 positivity.
Adamantinoma-like Ewing sarcoma. Diffuse p40 positivity.

Q: Histologically, Undifferentiated Sarcoma features a highly pleomorphic admixture of spindled, epithelioid, and polygonal cells, frequently containing multinucleated [...] with bubbly cytoplasm.
Pleomorphic sarcoma. It is not uncommon to have a mixture of epithelioid, spindled, and polygonal cells, showing easily identified pleomorphism.
Pleomorphic sarcoma. Multinucleated tumour giant cells may be seen, with bubbly cytoplasm. Eosinophilic globules may be noted in the cytoplasm of neoplastic cells.
A: tumor giant cells
Back Extra: Undifferentiated Sarcoma
- Clinical: Undifferentiated sarcoma commonly arises in the sinonasal tract, upper aerodigestive system, parotid gland region, and soft tissue of the neck. Rapid growth is common, and rare cases may present with regional or distant metastases.
- Micro: Tumours are composed of an admixture of spindle, epithelioid, and pleomorphic cells set in a variably collagenized extracellular matrix. Frequent mitotic figures, histiocyte-like cells, and giant tumour cells are observed.
- Ancillary: Immunohistochemically, there may be limited SMA reactivity, but h-caldesmon, desmin, S100, and epithelial markers are not expressed.
Reference Gallery:
Pleomorphic sarcoma. There is a large destructive mass filling the nasal cavity and expanding into the orbit and skull base in this CT image.
Pleomorphic sarcoma. The overlying epithelium is uninvolved, and the entire stroma is filled with an undifferentiated malignancy.
Pleomorphic sarcoma. It is not uncommon to have a mixture of epithelioid, spindled, and polygonal cells, showing easily identified pleomorphism.
Pleomorphic sarcoma. Multinucleated tumour giant cells may be seen, with bubbly cytoplasm. Eosinophilic globules may be noted in the cytoplasm of neoplastic cells.

Q: Radiographically, Undifferentiated Sarcoma of the head and neck often presents as a rapidly growing, highly [...] mass that commonly arises in the sinonasal tract.
Pleomorphic sarcoma. There is a large destructive mass filling the nasal cavity and expanding into the orbit and skull base in this CT image.
A: destructive
Back Extra: Undifferentiated Sarcoma
- Clinical: Undifferentiated sarcoma commonly arises in the sinonasal tract, upper aerodigestive system, parotid gland region, and soft tissue of the neck. Rapid growth is common, and rare cases may present with regional or distant metastases.
- Micro: Tumours are composed of an admixture of spindle, epithelioid, and pleomorphic cells set in a variably collagenized extracellular matrix. Frequent mitotic figures, histiocyte-like cells, and giant tumour cells are observed.
- Ancillary: Immunohistochemically, there may be limited SMA reactivity, but h-caldesmon, desmin, S100, and epithelial markers are not expressed.
Reference Gallery:
Pleomorphic sarcoma. There is a large destructive mass filling the nasal cavity and expanding into the orbit and skull base in this CT image.
Pleomorphic sarcoma. The overlying epithelium is uninvolved, and the entire stroma is filled with an undifferentiated malignancy.
Pleomorphic sarcoma. It is not uncommon to have a mixture of epithelioid, spindled, and polygonal cells, showing easily identified pleomorphism.
Pleomorphic sarcoma. Multinucleated tumour giant cells may be seen, with bubbly cytoplasm. Eosinophilic globules may be noted in the cytoplasm of neoplastic cells.

Q: At low magnification, a notable feature of sinonasal Undifferentiated Sarcoma is that the overlying surface [...] is typically uninvolved by the underlying malignant stromal proliferation.
Pleomorphic sarcoma. The overlying epithelium is uninvolved, and the entire stroma is filled with an undifferentiated malignancy.
A: epithelium
Back Extra: Undifferentiated Sarcoma
- Clinical: Undifferentiated sarcoma commonly arises in the sinonasal tract, upper aerodigestive system, parotid gland region, and soft tissue of the neck. Rapid growth is common, and rare cases may present with regional or distant metastases.
- Micro: Tumours are composed of an admixture of spindle, epithelioid, and pleomorphic cells set in a variably collagenized extracellular matrix. Frequent mitotic figures, histiocyte-like cells, and giant tumour cells are observed.
- Ancillary: Immunohistochemically, there may be limited SMA reactivity, but h-caldesmon, desmin, S100, and epithelial markers are not expressed.
Reference Gallery:
Pleomorphic sarcoma. There is a large destructive mass filling the nasal cavity and expanding into the orbit and skull base in this CT image.
Pleomorphic sarcoma. The overlying epithelium is uninvolved, and the entire stroma is filled with an undifferentiated malignancy.
Pleomorphic sarcoma. It is not uncommon to have a mixture of epithelioid, spindled, and polygonal cells, showing easily identified pleomorphism.
Pleomorphic sarcoma. Multinucleated tumour giant cells may be seen, with bubbly cytoplasm. Eosinophilic globules may be noted in the cytoplasm of neoplastic cells.

Q: Histologically, Angiosarcoma is characterized by highly pleomorphic endothelial cells that typically form irregular, tortuous, and freely [...] vascular channels.
Angiosarcoma. Freely anastomosing vessels are lined by highly pleomorphic endothelial cells associated with extravasated erythrocytes.
Angiosarcoma. The neoplastic cells show profound pleomorphism, with cytoplasmic vacuoles and eosinophilic globules, associated with neolumen formation and erythrocyte extravasation.
A: anastomosing
Back Extra: Angiosarcoma
- Clinical: Angiosarcoma often presents with nonspecific symptoms such as epistaxis, nasal obstruction, and sinusitis, and can invade vital structures.
- Micro: Angiosarcomas are characterized by tortuous, irregular vascular channels lined by pleomorphic endothelial cells, often with necrosis and hemorrhage.
- Ancillary: Immunohistochemistry shows strong and diffuse positivity for CD31, ERG, and CD34 in angiosarcoma.
Reference Gallery:
Angiosarcoma. A large, fleshy, haemorrhagic mass is present adjacent to the gingiva, histologically diagnosed as an angiosarcoma.
Angiosarcoma. An epithelioid proliferation of atypical cells makes up this angiosarcoma, with numerous neolumina identified.
Angiosarcoma. Freely anastomosing vessels are lined by highly pleomorphic endothelial cells associated with extravasated erythrocytes.
Angiosarcoma. The neoplastic cells show profound pleomorphism, with cytoplasmic vacuoles and eosinophilic globules, associated with neolumen formation and erythrocyte extravasation.
Angiosarcoma. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CD34.
Angiosarcoma. The neoplastic cells show a strong and diffuse nuclear reaction for ERG.
Angiosarcoma. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CD31.

Q: Strong and diffuse immunohistochemical positivity for CD31, CD34, and nuclear ERG in a malignant tumor forming irregular vascular channels is diagnostic of [...].
Angiosarcoma. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CD34.
Angiosarcoma. The neoplastic cells show a strong and diffuse nuclear reaction for ERG.
Angiosarcoma. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CD31.
A: Angiosarcoma
Back Extra: Angiosarcoma
- Clinical: Angiosarcoma often presents with nonspecific symptoms such as epistaxis, nasal obstruction, and sinusitis, and can invade vital structures.
- Micro: Angiosarcomas are characterized by tortuous, irregular vascular channels lined by pleomorphic endothelial cells, often with necrosis and hemorrhage.
- Ancillary: Immunohistochemistry shows strong and diffuse positivity for CD31, ERG, and CD34 in angiosarcoma.
Reference Gallery:
Angiosarcoma. A large, fleshy, haemorrhagic mass is present adjacent to the gingiva, histologically diagnosed as an angiosarcoma.
Angiosarcoma. An epithelioid proliferation of atypical cells makes up this angiosarcoma, with numerous neolumina identified.
Angiosarcoma. Freely anastomosing vessels are lined by highly pleomorphic endothelial cells associated with extravasated erythrocytes.
Angiosarcoma. The neoplastic cells show profound pleomorphism, with cytoplasmic vacuoles and eosinophilic globules, associated with neolumen formation and erythrocyte extravasation.
Angiosarcoma. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CD34.
Angiosarcoma. The neoplastic cells show a strong and diffuse nuclear reaction for ERG.
Angiosarcoma. The neoplastic cells show a strong and diffuse cytoplasmic reaction for CD31.

Q: Histologically, Epithelioid Hemangioendothelioma is characterized by cords of bland epithelioid or spindled cells in a myxohyaline stroma, often exhibiting characteristic [...] (sometimes referred to as "blister cells").
Epithelioid haemangioendothelioma. The bland-looking epithelioid cells are arranged in cords and nests showing typical glassy cytoplasm. Note the subtle vascular lumina.
Epithelioid haemangioendothelioma. Cells are more spindly and are loosely arranged in a fibrous matrix. Some cells show typical lumina (blister cells).
A: intracytoplasmic lumina
Q: Epithelioid Hemangioendothelioma
- Clinical: Patients with [...] often present with a slowly growing, sometimes painful mass due to vascular occlusion. Lymph node metastases are common.
- Micro: [...] is characterized by bland-looking epithelioid and spindle cells arranged in cords and strands in a myxohyaline stroma, with subtle intracytoplasmic lumina.
- Ancillary: [...] can be confirmed with molecular identification of the WWTR1::CAMTA1 or YAP1::TFE3 fusion genes.
Reference Gallery:
Epithelioid haemangioendothelioma. The bland-looking epithelioid cells are arranged in cords and nests showing typical glassy cytoplasm. Note the subtle vascular lumina.
Epithelioid haemangioendothelioma. Cells are more spindly and are loosely arranged in a fibrous matrix. Some cells show typical lumina (blister cells).
Epithelioid haemangioendothelioma. Most cases express CAMTA1, due to the WWTR1::CAMTA1 fusion.
A: epithelioid hemangioendothelioma; Epithelioid hemangioendothelioma; Epithelioid hemangioendothelioma

Q: The majority of Epithelioid Hemangioendothelioma cases show nuclear CAMTA1 positivity on immunohistochemistry, which is driven by the diagnostic [CAMTA1] gene fusion.
Epithelioid haemangioendothelioma. Most cases express CAMTA1, due to the WWTR1::CAMTA1 fusion.
A: WWTR1
Q: Epithelioid Hemangioendothelioma
- Clinical: Patients with [...] often present with a slowly growing, sometimes painful mass due to vascular occlusion. Lymph node metastases are common.
- Micro: [...] is characterized by bland-looking epithelioid and spindle cells arranged in cords and strands in a myxohyaline stroma, with subtle intracytoplasmic lumina.
- Ancillary: [...] can be confirmed with molecular identification of the WWTR1::CAMTA1 or YAP1::TFE3 fusion genes.
Reference Gallery:
Epithelioid haemangioendothelioma. The bland-looking epithelioid cells are arranged in cords and nests showing typical glassy cytoplasm. Note the subtle vascular lumina.
Epithelioid haemangioendothelioma. Cells are more spindly and are loosely arranged in a fibrous matrix. Some cells show typical lumina (blister cells).
Epithelioid haemangioendothelioma. Most cases express CAMTA1, due to the WWTR1::CAMTA1 fusion.
A: epithelioid hemangioendothelioma; Epithelioid hemangioendothelioma; Epithelioid hemangioendothelioma

Q: A slowly growing, erythematous nodule that microscopically shows a circumscribed proliferation of vessels lined by plump epithelioid endothelial cells with an inflammatory background is characteristic of [...].
Epithelioid haemangioma. An erythematous lower eyelid lesion has caused significant swelling.
Epithelioid haemangioma of the pinna. Low-power view demonstrates a rich vascular proliferation with lymphocytic infiltration below an intact epidermis.
A: Epithelioid Hemangioma
Back Extra: Epithelioid Hemangioma
- Clinical: Epithelioid hemangiomas are characterized by slowly growing, indolent, erythematous and violaceous nodules that are often pruritic or painful, and multifocal in about 15% of cases.
- Micro: Microscopically, the lesion shows a circumscribed, nodular to lobular proliferation of variably sized vessels lined by plump epithelioid endothelial cells with abundant eosinophilic cytoplasm and intracytoplasmic vacuoles (blister cells).
- Ancillary: Immunohistochemical expression of FOSB may be seen in about 50% of cases, and chromosomal translocations leading to FOS or FOSB rearrangements are common drivers of tumorigenesis.
Reference Gallery:
Epithelioid haemangioma. An erythematous lower eyelid lesion has caused significant swelling.
Epithelioid haemangioma of the pinna. Low-power view demonstrates a rich vascular proliferation with lymphocytic infiltration below an intact epidermis.
Epithelioid haemangioma. The epidermis is intact. There is a proliferation of vessels with endothelial cells projecting into the lumen. Note the eosinophils and lymphocytes.
Epithelioid haemangioma. Numerous intracytoplasmic vacuoles (blister cells) are noted in the endothelial cells. There is a background scattering of lymphocytes and eosinophils.

Q: The prominent, plump endothelial cells in Epithelioid Hemangioma frequently contain characteristic intracytoplasmic vacuoles, which are morphologically referred to as [...].
Epithelioid haemangioma. Numerous intracytoplasmic vacuoles (blister cells) are noted in the endothelial cells. There is a background scattering of lymphocytes and eosinophils.
A: blister cells
Back Extra: Epithelioid Hemangioma
- Clinical: Epithelioid hemangiomas are characterized by slowly growing, indolent, erythematous and violaceous nodules that are often pruritic or painful, and multifocal in about 15% of cases.
- Micro: Microscopically, the lesion shows a circumscribed, nodular to lobular proliferation of variably sized vessels lined by plump epithelioid endothelial cells with abundant eosinophilic cytoplasm and intracytoplasmic vacuoles (blister cells).
- Ancillary: Immunohistochemical expression of FOSB may be seen in about 50% of cases, and chromosomal translocations leading to FOS or FOSB rearrangements are common drivers of tumorigenesis.
Reference Gallery:
Epithelioid haemangioma. An erythematous lower eyelid lesion has caused significant swelling.
Epithelioid haemangioma of the pinna. Low-power view demonstrates a rich vascular proliferation with lymphocytic infiltration below an intact epidermis.
Epithelioid haemangioma. The epidermis is intact. There is a proliferation of vessels with endothelial cells projecting into the lumen. Note the eosinophils and lymphocytes.
Epithelioid haemangioma. Numerous intracytoplasmic vacuoles (blister cells) are noted in the endothelial cells. There is a background scattering of lymphocytes and eosinophils.

Q: In addition to the lobular vascular proliferation, the background stroma of Epithelioid Hemangioma typically contains a prominent inflammatory infiltrate composed predominantly of lymphocytes and [...].
Epithelioid haemangioma. The epidermis is intact. There is a proliferation of vessels with endothelial cells projecting into the lumen. Note the eosinophils and lymphocytes.
Epithelioid haemangioma. Numerous intracytoplasmic vacuoles (blister cells) are noted in the endothelial cells. There is a background scattering of lymphocytes and eosinophils.
A: eosinophils
Back Extra: Epithelioid Hemangioma
- Clinical: Epithelioid hemangiomas are characterized by slowly growing, indolent, erythematous and violaceous nodules that are often pruritic or painful, and multifocal in about 15% of cases.
- Micro: Microscopically, the lesion shows a circumscribed, nodular to lobular proliferation of variably sized vessels lined by plump epithelioid endothelial cells with abundant eosinophilic cytoplasm and intracytoplasmic vacuoles (blister cells).
- Ancillary: Immunohistochemical expression of FOSB may be seen in about 50% of cases, and chromosomal translocations leading to FOS or FOSB rearrangements are common drivers of tumorigenesis.
Reference Gallery:
Epithelioid haemangioma. An erythematous lower eyelid lesion has caused significant swelling.
Epithelioid haemangioma of the pinna. Low-power view demonstrates a rich vascular proliferation with lymphocytic infiltration below an intact epidermis.
Epithelioid haemangioma. The epidermis is intact. There is a proliferation of vessels with endothelial cells projecting into the lumen. Note the eosinophils and lymphocytes.
Epithelioid haemangioma. Numerous intracytoplasmic vacuoles (blister cells) are noted in the endothelial cells. There is a background scattering of lymphocytes and eosinophils.

Q: Microscopically, the lobular capillary variant of Haemangioma is classically characterized by tightly packed capillaries arranged around central [...].
Lobular capillary haemangioma. Lobules are composed of tightly packed capillaries around central patulous vessels. Inflammation is minimal in this illustration.
Lobular capillary haemangioma. A larger central vessel is surrounded by a variably cellular proliferation of capillary-sized vessels and pericytic cells, associated with stromal fibrosis and haemorrhage.
A: patulous vessels
Back Extra: Haemangioma
- Clinical: Haemangiomas commonly present as red haemorrhagic papules in the oral cavity and as unilateral epistaxis or obstructive masses in the sinonasal tract.
- Micro: Lobular capillary haemangiomas are characterized by a lobular architecture of tightly packed capillaries around central patulous vessels, surrounded by a fibromyxoid stroma.
- Ancillary: Immunohistochemistry shows neoplastic cells positive for CD34, CD31, ERG, FLI1, and von Willebrand factor.
Reference Gallery:
Lobular capillary haemangioma. Sagittal T2-weighted fat-suppressed MRI of a Little area sinonasal tract haemangioma, showing bright signal intensity.
Lobular capillary haemangioma. Low-power view shows surface ulceration. There are many central vessels surrounded by a cellular vascular proliferation arranged in a lobular architecture.
Lobular capillary haemangioma. Lobules are composed of tightly packed capillaries around central patulous vessels. Inflammation is minimal in this illustration.
Lobular capillary haemangioma. A larger central vessel is surrounded by a variably cellular proliferation of capillary-sized vessels and pericytic cells, associated with stromal fibrosis and haemorrhage.
Lobular capillary haemangioma. Stromal hyalinization, oedema, and myxoid change may sometimes be the dominant finding, although the rich vascularity is still easy to identify.
Cavernous haemangioma. A circumscribed vascular lesion composed of cavernous spaces, located in the dermis and subcutis of the neck.

Q: A highly characteristic finding in the sinonasal presentation of Haemangioma is a distinct [...] architecture of tightly packed capillaries on histology, which classically corresponds to a bright signal intensity on T2-weighted MRI.
Lobular capillary haemangioma. Sagittal T2-weighted fat-suppressed MRI of a Little area sinonasal tract haemangioma, showing bright signal intensity.
Lobular capillary haemangioma. Low-power view shows surface ulceration. There are many central vessels surrounded by a cellular vascular proliferation arranged in a lobular architecture.
A: lobular
Back Extra: Haemangioma
- Clinical: Haemangiomas commonly present as red haemorrhagic papules in the oral cavity and as unilateral epistaxis or obstructive masses in the sinonasal tract.
- Micro: Lobular capillary haemangiomas are characterized by a lobular architecture of tightly packed capillaries around central patulous vessels, surrounded by a fibromyxoid stroma.
- Ancillary: Immunohistochemistry shows neoplastic cells positive for CD34, CD31, ERG, FLI1, and von Willebrand factor.
Reference Gallery:
Lobular capillary haemangioma. Sagittal T2-weighted fat-suppressed MRI of a Little area sinonasal tract haemangioma, showing bright signal intensity.
Lobular capillary haemangioma. Low-power view shows surface ulceration. There are many central vessels surrounded by a cellular vascular proliferation arranged in a lobular architecture.
Lobular capillary haemangioma. Lobules are composed of tightly packed capillaries around central patulous vessels. Inflammation is minimal in this illustration.
Lobular capillary haemangioma. A larger central vessel is surrounded by a variably cellular proliferation of capillary-sized vessels and pericytic cells, associated with stromal fibrosis and haemorrhage.
Lobular capillary haemangioma. Stromal hyalinization, oedema, and myxoid change may sometimes be the dominant finding, although the rich vascularity is still easy to identify.
Cavernous haemangioma. A circumscribed vascular lesion composed of cavernous spaces, located in the dermis and subcutis of the neck.

Q: The cavernous variant of Haemangioma is a circumscribed vascular lesion that is microscopically defined by the presence of large, dilated [...] within the dermis or subcutis.
Cavernous haemangioma. A circumscribed vascular lesion composed of cavernous spaces, located in the dermis and subcutis of the neck.
A: cavernous spaces
Back Extra: Haemangioma
- Clinical: Haemangiomas commonly present as red haemorrhagic papules in the oral cavity and as unilateral epistaxis or obstructive masses in the sinonasal tract.
- Micro: Lobular capillary haemangiomas are characterized by a lobular architecture of tightly packed capillaries around central patulous vessels, surrounded by a fibromyxoid stroma.
- Ancillary: Immunohistochemistry shows neoplastic cells positive for CD34, CD31, ERG, FLI1, and von Willebrand factor.
Reference Gallery:
Lobular capillary haemangioma. Sagittal T2-weighted fat-suppressed MRI of a Little area sinonasal tract haemangioma, showing bright signal intensity.
Lobular capillary haemangioma. Low-power view shows surface ulceration. There are many central vessels surrounded by a cellular vascular proliferation arranged in a lobular architecture.
Lobular capillary haemangioma. Lobules are composed of tightly packed capillaries around central patulous vessels. Inflammation is minimal in this illustration.
Lobular capillary haemangioma. A larger central vessel is surrounded by a variably cellular proliferation of capillary-sized vessels and pericytic cells, associated with stromal fibrosis and haemorrhage.
Lobular capillary haemangioma. Stromal hyalinization, oedema, and myxoid change may sometimes be the dominant finding, although the rich vascularity is still easy to identify.
Cavernous haemangioma. A circumscribed vascular lesion composed of cavernous spaces, located in the dermis and subcutis of the neck.

Q: The definitive diagnosis of Kaposi Sarcoma is confirmed by strong nuclear immunohistochemical expression of [...] in the neoplastic spindle cells.
Kaposi sarcoma. Oral. All of the neoplastic cells show a strong and diffuse nuclear expression of KSHV/HHV8, confirming the diagnosis of Kaposi sarcoma.
Kaposi sarcoma. Only the nuclei of the neoplastic cells show immunoreactivity for KSHV/HHV8, whereas the native endothelial cells are negative, a finding that helps to confirm the diagnosis.
A: KSHV/HHV8
Back Extra: Kaposi Sarcoma
- Clinical: Kaposi Sarcoma forms multiple reddish to purple macules that progress to plaques or nodules, often seen in patients with HIV/AIDS, especially in men who have sex with men.
- Micro: Early lesions show a subtle proliferation of small, slit-like vascular spaces with extravasated erythrocytes and a lymphoplasmacytic infiltrate. Advanced stages show unencapsulated infiltrating fascicles of spindle cells with atypia and mitoses.
- Ancillary: Diagnostic features include the presence of hyaline globules and strong nuclear KSHV/HHV8 expression in neoplastic cells.
Reference Gallery:
Oral Kaposi sarcoma. Gingival and tongue purple vascular lesions are noted in this HIV-positive patient.
Kaposi sarcoma. Laryngeal. This hypercellular, fascicular arrangement of neoplastic spindled cells shows extravasated erythrocytes.
Kaposi sarcoma. Oral. Intracytoplasmic eosinophilic globules are frequently seen in Kaposi sarcoma. Erythrocytes are easily identified throughout.
Kaposi sarcoma. Laryngeal. There is moderate nuclear pleomorphism in spindled neoplastic cells that show numerous large intracytoplasmic eosinophilic globules.
Kaposi sarcoma. Oral. All of the neoplastic cells show a strong and diffuse nuclear expression of KSHV/HHV8, confirming the diagnosis of Kaposi sarcoma.
Kaposi sarcoma. This oral cavity Kaposi sarcoma demonstrates a lymphangioma-like appearance, although spindled neoplastic cells are also seen.
Kaposi sarcoma. The vasoformative appearance of the neoplastic cells can be appreciated here, with dilated lumina. Extravasated erythrocytes are noted.
Kaposi sarcoma. Only the nuclei of the neoplastic cells show immunoreactivity for KSHV/HHV8, whereas the native endothelial cells are negative, a finding that helps to confirm the diagnosis.
Oral Kaposi sarcoma. Nodular Kaposi sarcoma of the palate.

Q: Microscopically, the spindle cells in Kaposi Sarcoma frequently contain characteristic intracytoplasmic, eosinophilic [...].
Kaposi sarcoma. Oral. Intracytoplasmic eosinophilic globules are frequently seen in Kaposi sarcoma. Erythrocytes are easily identified throughout.
Kaposi sarcoma. Laryngeal. There is moderate nuclear pleomorphism in spindled neoplastic cells that show numerous large intracytoplasmic eosinophilic globules.
A: hyaline globules
Back Extra: Kaposi Sarcoma
- Clinical: Kaposi Sarcoma forms multiple reddish to purple macules that progress to plaques or nodules, often seen in patients with HIV/AIDS, especially in men who have sex with men.
- Micro: Early lesions show a subtle proliferation of small, slit-like vascular spaces with extravasated erythrocytes and a lymphoplasmacytic infiltrate. Advanced stages show unencapsulated infiltrating fascicles of spindle cells with atypia and mitoses.
- Ancillary: Diagnostic features include the presence of hyaline globules and strong nuclear KSHV/HHV8 expression in neoplastic cells.
Reference Gallery:
Oral Kaposi sarcoma. Gingival and tongue purple vascular lesions are noted in this HIV-positive patient.
Kaposi sarcoma. Laryngeal. This hypercellular, fascicular arrangement of neoplastic spindled cells shows extravasated erythrocytes.
Kaposi sarcoma. Oral. Intracytoplasmic eosinophilic globules are frequently seen in Kaposi sarcoma. Erythrocytes are easily identified throughout.
Kaposi sarcoma. Laryngeal. There is moderate nuclear pleomorphism in spindled neoplastic cells that show numerous large intracytoplasmic eosinophilic globules.
Kaposi sarcoma. Oral. All of the neoplastic cells show a strong and diffuse nuclear expression of KSHV/HHV8, confirming the diagnosis of Kaposi sarcoma.
Kaposi sarcoma. This oral cavity Kaposi sarcoma demonstrates a lymphangioma-like appearance, although spindled neoplastic cells are also seen.
Kaposi sarcoma. The vasoformative appearance of the neoplastic cells can be appreciated here, with dilated lumina. Extravasated erythrocytes are noted.
Kaposi sarcoma. Only the nuclei of the neoplastic cells show immunoreactivity for KSHV/HHV8, whereas the native endothelial cells are negative, a finding that helps to confirm the diagnosis.
Oral Kaposi sarcoma. Nodular Kaposi sarcoma of the palate.

Q: A classic histologic hallmark of Kaposi Sarcoma is the proliferation of slit-like vascular spaces that characteristically contain [...].
Kaposi sarcoma. Laryngeal. This hypercellular, fascicular arrangement of neoplastic spindled cells shows extravasated erythrocytes.
Kaposi sarcoma. The vasoformative appearance of the neoplastic cells can be appreciated here, with dilated lumina. Extravasated erythrocytes are noted.
A: extravasated erythrocytes
Back Extra: Kaposi Sarcoma
- Clinical: Kaposi Sarcoma forms multiple reddish to purple macules that progress to plaques or nodules, often seen in patients with HIV/AIDS, especially in men who have sex with men.
- Micro: Early lesions show a subtle proliferation of small, slit-like vascular spaces with extravasated erythrocytes and a lymphoplasmacytic infiltrate. Advanced stages show unencapsulated infiltrating fascicles of spindle cells with atypia and mitoses.
- Ancillary: Diagnostic features include the presence of hyaline globules and strong nuclear KSHV/HHV8 expression in neoplastic cells.
Reference Gallery:
Oral Kaposi sarcoma. Gingival and tongue purple vascular lesions are noted in this HIV-positive patient.
Kaposi sarcoma. Laryngeal. This hypercellular, fascicular arrangement of neoplastic spindled cells shows extravasated erythrocytes.
Kaposi sarcoma. Oral. Intracytoplasmic eosinophilic globules are frequently seen in Kaposi sarcoma. Erythrocytes are easily identified throughout.
Kaposi sarcoma. Laryngeal. There is moderate nuclear pleomorphism in spindled neoplastic cells that show numerous large intracytoplasmic eosinophilic globules.
Kaposi sarcoma. Oral. All of the neoplastic cells show a strong and diffuse nuclear expression of KSHV/HHV8, confirming the diagnosis of Kaposi sarcoma.
Kaposi sarcoma. This oral cavity Kaposi sarcoma demonstrates a lymphangioma-like appearance, although spindled neoplastic cells are also seen.
Kaposi sarcoma. The vasoformative appearance of the neoplastic cells can be appreciated here, with dilated lumina. Extravasated erythrocytes are noted.
Kaposi sarcoma. Only the nuclei of the neoplastic cells show immunoreactivity for KSHV/HHV8, whereas the native endothelial cells are negative, a finding that helps to confirm the diagnosis.
Oral Kaposi sarcoma. Nodular Kaposi sarcoma of the palate.

Q: Microscopically, Lymphangioma typically presents with variably sized, irregular, thin-walled, fluid-filled spaces lined by [...].
Lymphangioma. This papillary mucosal lesion shows accumulation of dilated lymphatic vessels and, focally, small clusters of lymphocytes.
Lymphangioma. This lesion located next to the parotid gland of a newborn consists of cystically dilated lymphatic channels.
A: lymphatic endothelium
Back Extra: Lymphangioma
- Clinical: Lymphangiomas are most commonly diagnosed in infancy and early childhood, with symptoms related to lesion size and involvement of surrounding structures.
- Micro: Microscopically, lymphangiomas show variably sized, irregular, thin-walled, fluid-filled spaces lined by lymphatic endothelium, surrounded by fibrous, smooth muscle, and adipose tissue.
- Ancillary: D2-40 is a useful marker for confirming the lymphatic nature of the vessels in lymphangiomas.
Reference Gallery:
Lymphangioma. This papillary mucosal lesion shows accumulation of dilated lymphatic vessels and, focally, small clusters of lymphocytes.
Lymphangioma. D2-40 highlights the lymphatic nature of the vessels.
Lymphangioma. This lesion located next to the parotid gland of a newborn consists of cystically dilated lymphatic channels.

Q: To confirm the lymphatic nature of the vascular channels in Lymphangioma, the highly specific immunohistochemical marker [...] is commonly utilized.
Lymphangioma. D2-40 highlights the lymphatic nature of the vessels.
A: D2-40
Back Extra: Lymphangioma
- Clinical: Lymphangiomas are most commonly diagnosed in infancy and early childhood, with symptoms related to lesion size and involvement of surrounding structures.
- Micro: Microscopically, lymphangiomas show variably sized, irregular, thin-walled, fluid-filled spaces lined by lymphatic endothelium, surrounded by fibrous, smooth muscle, and adipose tissue.
- Ancillary: D2-40 is a useful marker for confirming the lymphatic nature of the vessels in lymphangiomas.
Reference Gallery:
Lymphangioma. This papillary mucosal lesion shows accumulation of dilated lymphatic vessels and, focally, small clusters of lymphocytes.
Lymphangioma. D2-40 highlights the lymphatic nature of the vessels.
Lymphangioma. This lesion located next to the parotid gland of a newborn consists of cystically dilated lymphatic channels.