Title: WHO / BST
Tags: BST::Soft_Tissue::Fibroblastic BST::Soft_Tissue::Uncertain_Diff BST::Bone::Chondrogenic BST::Soft_Tissue::Adipocytic BST::Soft_Tissue::Vascular BST::Bone::Other BST::Soft_Tissue::Nerve_Sheath BST::Bone::Osteogenic BST::Soft_Tissue::Fibrohistiocytic BST::Soft_Tissue::Skeletal_Muscle BST::Bone::Vascular BST::Bone::Hematolymphoid BST::Bone::Notochordal BST::Syndromes::Predisposition BST::Soft_Tissue::Smooth_Muscle BST::Soft_Tissue::Pericytic BST::Bone::Fibrogenic

Q: Histologically, Bizarre Parosteal Osteochondromatous Proliferation features a disordered mixture of cartilage, bone, and fibrous tissue that frequently contains a distinct, deeply basophilic osteoid matrix known as [...].
Bizarre parosteal osteochondromatous proliferation. So-called blue bone is characteristic.
Bizarre parosteal osteochondromatous proliferation. Bizarre parosteal osteochondromatous proliferation with a more disorganized mixture of mainly bone and cartilage.
A: "blue bone"
Back Extra: Bizarre Parosteal Osteochondromatous Proliferation
- Clinical: Bizarre Parosteal Osteochondromatous Proliferation typically presents as a painless mass, often present for months to years, and radiologically appears as a well-circumscribed calcified mass attached to the cortical surface.
- Micro: Histopathologically, Bizarre Parosteal Osteochondromatous Proliferation is characterized by a mixture of cartilage, bone, and fibrous tissue with an outer hyaline cartilage cap and a characteristic 'blue bone' stroma.
- Ancillary: Recurrent cytogenetic abnormalities in Bizarre Parosteal Osteochondromatous Proliferation include t(1;17)(q32;q21), inv(7), and inv(6).
Reference Gallery:
Bizarre parosteal osteochondromatous proliferation. Gross specimen showing a bony stalk with cartilaginous surface.
Bizarre parosteal osteochondromatous proliferation. Low-power view showing bony stalk covered by cartilaginous cap.
Bizarre parosteal osteochondromatous proliferation. Cartilage often looks atypical with an increased number of chondrocytes with enlarged nuclei.
Bizarre parosteal osteochondromatous proliferation. Spindle cell proliferation with osteoid formation.
Bizarre parosteal osteochondromatous proliferation. So-called blue bone is characteristic.
Bizarre parosteal osteochondromatous proliferation. CT shows a calcified mass attached to the intact cortex of the ulna.
Bizarre parosteal osteochondromatous proliferation. On the radial side of the proximal phalanx, a soft tissue swelling with some calcifications and mature bone is seen superficial and contiguous to an intact cortex. There are no signs of osteochondroma.
Bizarre parosteal osteochondromatous proliferation. On the dorsal surface of the middle phalanx, mature bone is seen closest to a normal underlying cortex. In the periphery, more fluffy calcifications are present. A lucent demarcation line projects between cortex and the bizarre parosteal osteochondromatous proliferation.
Bizarre parosteal osteochondromatous proliferation. Bizarre parosteal osteochondromatous proliferation with a more disorganized mixture of mainly bone and cartilage.

Q: Radiographically, Bizarre Parosteal Osteochondromatous Proliferation typically presents as a calcified surface mass that is attached to an [...] underlying cortex, which helps distinguish it from an osteochondroma.
Bizarre parosteal osteochondromatous proliferation. CT shows a calcified mass attached to the intact cortex of the ulna.
Bizarre parosteal osteochondromatous proliferation. On the radial side of the proximal phalanx, a soft tissue swelling with some calcifications and mature bone is seen superficial and contiguous to an intact cortex. There are no signs of osteochondroma.
Bizarre parosteal osteochondromatous proliferation. On the dorsal surface of the middle phalanx, mature bone is seen closest to a normal underlying cortex. In the periphery, more fluffy calcifications are present. A lucent demarcation line projects between cortex and the bizarre parosteal osteochondromatous proliferation.
A: intact
Back Extra: Bizarre Parosteal Osteochondromatous Proliferation
- Clinical: Bizarre Parosteal Osteochondromatous Proliferation typically presents as a painless mass, often present for months to years, and radiologically appears as a well-circumscribed calcified mass attached to the cortical surface.
- Micro: Histopathologically, Bizarre Parosteal Osteochondromatous Proliferation is characterized by a mixture of cartilage, bone, and fibrous tissue with an outer hyaline cartilage cap and a characteristic 'blue bone' stroma.
- Ancillary: Recurrent cytogenetic abnormalities in Bizarre Parosteal Osteochondromatous Proliferation include t(1;17)(q32;q21), inv(7), and inv(6).
Reference Gallery:
Bizarre parosteal osteochondromatous proliferation. Gross specimen showing a bony stalk with cartilaginous surface.
Bizarre parosteal osteochondromatous proliferation. Low-power view showing bony stalk covered by cartilaginous cap.
Bizarre parosteal osteochondromatous proliferation. Cartilage often looks atypical with an increased number of chondrocytes with enlarged nuclei.
Bizarre parosteal osteochondromatous proliferation. Spindle cell proliferation with osteoid formation.
Bizarre parosteal osteochondromatous proliferation. So-called blue bone is characteristic.
Bizarre parosteal osteochondromatous proliferation. CT shows a calcified mass attached to the intact cortex of the ulna.
Bizarre parosteal osteochondromatous proliferation. On the radial side of the proximal phalanx, a soft tissue swelling with some calcifications and mature bone is seen superficial and contiguous to an intact cortex. There are no signs of osteochondroma.
Bizarre parosteal osteochondromatous proliferation. On the dorsal surface of the middle phalanx, mature bone is seen closest to a normal underlying cortex. In the periphery, more fluffy calcifications are present. A lucent demarcation line projects between cortex and the bizarre parosteal osteochondromatous proliferation.
Bizarre parosteal osteochondromatous proliferation. Bizarre parosteal osteochondromatous proliferation with a more disorganized mixture of mainly bone and cartilage.

Q: The cartilaginous component of Bizarre Parosteal Osteochondromatous Proliferation often appears irregular and features increased cellularity with [...] within the chondrocytes, inspiring the "bizarre" moniker.
Bizarre parosteal osteochondromatous proliferation. Low-power view showing bony stalk covered by cartilaginous cap.
Bizarre parosteal osteochondromatous proliferation. Cartilage often looks atypical with an increased number of chondrocytes with enlarged nuclei.
A: enlarged, atypical nuclei
Back Extra: Bizarre Parosteal Osteochondromatous Proliferation
- Clinical: Bizarre Parosteal Osteochondromatous Proliferation typically presents as a painless mass, often present for months to years, and radiologically appears as a well-circumscribed calcified mass attached to the cortical surface.
- Micro: Histopathologically, Bizarre Parosteal Osteochondromatous Proliferation is characterized by a mixture of cartilage, bone, and fibrous tissue with an outer hyaline cartilage cap and a characteristic 'blue bone' stroma.
- Ancillary: Recurrent cytogenetic abnormalities in Bizarre Parosteal Osteochondromatous Proliferation include t(1;17)(q32;q21), inv(7), and inv(6).
Reference Gallery:
Bizarre parosteal osteochondromatous proliferation. Gross specimen showing a bony stalk with cartilaginous surface.
Bizarre parosteal osteochondromatous proliferation. Low-power view showing bony stalk covered by cartilaginous cap.
Bizarre parosteal osteochondromatous proliferation. Cartilage often looks atypical with an increased number of chondrocytes with enlarged nuclei.
Bizarre parosteal osteochondromatous proliferation. Spindle cell proliferation with osteoid formation.
Bizarre parosteal osteochondromatous proliferation. So-called blue bone is characteristic.
Bizarre parosteal osteochondromatous proliferation. CT shows a calcified mass attached to the intact cortex of the ulna.
Bizarre parosteal osteochondromatous proliferation. On the radial side of the proximal phalanx, a soft tissue swelling with some calcifications and mature bone is seen superficial and contiguous to an intact cortex. There are no signs of osteochondroma.
Bizarre parosteal osteochondromatous proliferation. On the dorsal surface of the middle phalanx, mature bone is seen closest to a normal underlying cortex. In the periphery, more fluffy calcifications are present. A lucent demarcation line projects between cortex and the bizarre parosteal osteochondromatous proliferation.
Bizarre parosteal osteochondromatous proliferation. Bizarre parosteal osteochondromatous proliferation with a more disorganized mixture of mainly bone and cartilage.

Q: Radiographically, Chondroblastoma typically presents as an eccentric, well-defined lytic lesion that classically arises in the [...] of long bones, frequently accompanied by surrounding marrow edema.
Chondroblastoma. Lateral radiograph showing a lytic lesion in the distal femoral epiphysis.
Chondroblastoma. Sagittal short-tau inversion recovery (STIR) MRI showing a well-defined lesion of increased signal in the epiphysis, with similar, oedema-like, high signal in the adjacent marrow and soft tissues.
A: epiphysis
Back Extra: Chondroblastoma
- Clinical: Chondroblastoma typically presents with pain and local tenderness, often associated with joint effusion and impaired movement.
- Micro: Histologically, chondroblastomas are characterized by sheets of ovoid to polygonal cells with small grooved nuclei and eosinophilic cytoplasm, along with osteoclast-like giant cells and areas of matrix calcification.
- Ancillary: Immunohistochemistry using an antibody against H3.3 p.Lys36Met (K36M) shows diffuse nuclear expression in chondroblastoma cells, which is a helpful diagnostic marker.
Reference Gallery:
Chondroblastoma. Lateral radiograph showing a lytic lesion in the distal femoral epiphysis.
Chondroblastoma. Sagittal short-tau inversion recovery (STIR) MRI showing a well-defined lesion of increased signal in the epiphysis, with similar, oedema-like, high signal in the adjacent marrow and soft tissues.
Chondroblastoma. Axial CT of patella showing an eccentric well-defined lytic lesion.
Chondroblastoma. Sheets of chondroblastic oval to polygonal cells, osteoclast-like giant cells, and an area of matrix calcification.
Chondroblastoma. Oval to polygonal chondroblasts with well-defined cytoplasmic borders, merging with an area of eosinophilic cartilaginous matrix.
Chondroblastoma. Chondroblastic cells with nuclear indentation and grooves. The top-right corner shows chicken-wire pericellular calcification.
Chondroblastoma. H3.3 p.Lys36Met (K36M) diffuse nuclear expression in the chondroblastic cells. Note that the osteoclast-like giant cells show no expression.

Q: Histologically, Chondroblastoma is characterized by sheets of ovoid to polygonal cells with nuclear grooves, often featuring a distinct pericellular matrix mineralization pattern known as [...].
Chondroblastoma. Sheets of chondroblastic oval to polygonal cells, osteoclast-like giant cells, and an area of matrix calcification.
Chondroblastoma. Chondroblastic cells with nuclear indentation and grooves. The top-right corner shows chicken-wire pericellular calcification.
A: "chicken-wire" calcification
Back Extra: Chondroblastoma
- Clinical: Chondroblastoma typically presents with pain and local tenderness, often associated with joint effusion and impaired movement.
- Micro: Histologically, chondroblastomas are characterized by sheets of ovoid to polygonal cells with small grooved nuclei and eosinophilic cytoplasm, along with osteoclast-like giant cells and areas of matrix calcification.
- Ancillary: Immunohistochemistry using an antibody against H3.3 p.Lys36Met (K36M) shows diffuse nuclear expression in chondroblastoma cells, which is a helpful diagnostic marker.
Reference Gallery:
Chondroblastoma. Lateral radiograph showing a lytic lesion in the distal femoral epiphysis.
Chondroblastoma. Sagittal short-tau inversion recovery (STIR) MRI showing a well-defined lesion of increased signal in the epiphysis, with similar, oedema-like, high signal in the adjacent marrow and soft tissues.
Chondroblastoma. Axial CT of patella showing an eccentric well-defined lytic lesion.
Chondroblastoma. Sheets of chondroblastic oval to polygonal cells, osteoclast-like giant cells, and an area of matrix calcification.
Chondroblastoma. Oval to polygonal chondroblasts with well-defined cytoplasmic borders, merging with an area of eosinophilic cartilaginous matrix.
Chondroblastoma. Chondroblastic cells with nuclear indentation and grooves. The top-right corner shows chicken-wire pericellular calcification.
Chondroblastoma. H3.3 p.Lys36Met (K36M) diffuse nuclear expression in the chondroblastic cells. Note that the osteoclast-like giant cells show no expression.

Q: A highly specific diagnostic marker for Chondroblastoma is diffuse nuclear expression of [...] by immunohistochemistry, which highlights the mononuclear neoplastic cells but not the reactive osteoclast-like giant cells.
Chondroblastoma. H3.3 p.Lys36Met (K36M) diffuse nuclear expression in the chondroblastic cells. Note that the osteoclast-like giant cells show no expression.
A: H3.3 K36M
Back Extra: Chondroblastoma
- Clinical: Chondroblastoma typically presents with pain and local tenderness, often associated with joint effusion and impaired movement.
- Micro: Histologically, chondroblastomas are characterized by sheets of ovoid to polygonal cells with small grooved nuclei and eosinophilic cytoplasm, along with osteoclast-like giant cells and areas of matrix calcification.
- Ancillary: Immunohistochemistry using an antibody against H3.3 p.Lys36Met (K36M) shows diffuse nuclear expression in chondroblastoma cells, which is a helpful diagnostic marker.
Reference Gallery:
Chondroblastoma. Lateral radiograph showing a lytic lesion in the distal femoral epiphysis.
Chondroblastoma. Sagittal short-tau inversion recovery (STIR) MRI showing a well-defined lesion of increased signal in the epiphysis, with similar, oedema-like, high signal in the adjacent marrow and soft tissues.
Chondroblastoma. Axial CT of patella showing an eccentric well-defined lytic lesion.
Chondroblastoma. Sheets of chondroblastic oval to polygonal cells, osteoclast-like giant cells, and an area of matrix calcification.
Chondroblastoma. Oval to polygonal chondroblasts with well-defined cytoplasmic borders, merging with an area of eosinophilic cartilaginous matrix.
Chondroblastoma. Chondroblastic cells with nuclear indentation and grooves. The top-right corner shows chicken-wire pericellular calcification.
Chondroblastoma. H3.3 p.Lys36Met (K36M) diffuse nuclear expression in the chondroblastic cells. Note that the osteoclast-like giant cells show no expression.

Q: Microscopically, Chondromyxoid Fibroma features a distinct lobular architecture composed of myxoid tissue with hypercellular peripheries and [...].
Chondromyxoid fibroma. Lobular architecture. In addition to myxoid areas, areas with more hyaline cartilaginous matrix can be seen in a subset of cases.
Chondromyxoid fibroma. Stellate cells embedded in a myxoid matrix are seen on the right, with more-cellular areas containing round cells and multinucleated giant cells on the left.
A: hypocellular centers
Back Extra: Chondromyxoid Fibroma
- Clinical: Pain is the most common symptom, and the lesion is typically a well-demarcated, oval-shaped, lobulated osteolytic, eccentric, and metaphyseally located lesion, with attenuation and expansion of the cortex.
- Micro: Lobules demonstrate hypocellular centres with hypercellular peripheries, and stellate or spindle-shaped cells in a myxoid background. Calcification, when present, is usually coarse.
- Ancillary: Molecular analysis can identify upregulation of GRM1 expression, a specific diagnostic adjunct in distinguishing this entity from its mimics.
Reference Gallery:
Chondromyxoid fibroma. Radiograph shows an eccentrically localized, expansile mixed osteolytic-sclerotic tumour with a well-defined sclerotic margin in the metaphysis and proximal diaphysis of the tibia. The combination of these morphological characteristics with the location is indicative of chondromyxoid fibroma.
Chondromyxoid fibroma. The myxoid components have a high signal intensity on the T2-weighted fat-suppressed images. Note the reactive high signal surrounding the tumour in the bone marrow and in the periosteum medially.
Chondromyxoid fibroma. Stellate cells embedded in a myxoid matrix are seen on the right, with more-cellular areas containing round cells and multinucleated giant cells on the left.
Chondromyxoid fibroma. Moderate nuclear enlargement may be present. The eosinophilic cytoplasmic processes are evident.
Chondromyxoid fibroma. Lobular architecture. In addition to myxoid areas, areas with more hyaline cartilaginous matrix can be seen in a subset of cases.
Chondromyxoid fibroma of the ilium. Note the yellowish-grey, relatively uniform lesion, with sharply demarcated borders and expansion of the bone.
Chondromyxoid fibroma. Focal coarse calcification.

Q: Radiographically, Chondromyxoid Fibroma typically presents as a well-demarcated, expansile, osteolytic tumor characteristically situated in an [...] location within the metaphysis.
Chondromyxoid fibroma. Radiograph shows an eccentrically localized, expansile mixed osteolytic-sclerotic tumour with a well-defined sclerotic margin in the metaphysis and proximal diaphysis of the tibia. The combination of these morphological characteristics with the location is indicative of chondromyxoid fibroma.
Chondromyxoid fibroma. The myxoid components have a high signal intensity on the T2-weighted fat-suppressed images. Note the reactive high signal surrounding the tumour in the bone marrow and in the periosteum medially.
A: eccentric
Back Extra: Chondromyxoid Fibroma
- Clinical: Pain is the most common symptom, and the lesion is typically a well-demarcated, oval-shaped, lobulated osteolytic, eccentric, and metaphyseally located lesion, with attenuation and expansion of the cortex.
- Micro: Lobules demonstrate hypocellular centres with hypercellular peripheries, and stellate or spindle-shaped cells in a myxoid background. Calcification, when present, is usually coarse.
- Ancillary: Molecular analysis can identify upregulation of GRM1 expression, a specific diagnostic adjunct in distinguishing this entity from its mimics.
Reference Gallery:
Chondromyxoid fibroma. Radiograph shows an eccentrically localized, expansile mixed osteolytic-sclerotic tumour with a well-defined sclerotic margin in the metaphysis and proximal diaphysis of the tibia. The combination of these morphological characteristics with the location is indicative of chondromyxoid fibroma.
Chondromyxoid fibroma. The myxoid components have a high signal intensity on the T2-weighted fat-suppressed images. Note the reactive high signal surrounding the tumour in the bone marrow and in the periosteum medially.
Chondromyxoid fibroma. Stellate cells embedded in a myxoid matrix are seen on the right, with more-cellular areas containing round cells and multinucleated giant cells on the left.
Chondromyxoid fibroma. Moderate nuclear enlargement may be present. The eosinophilic cytoplasmic processes are evident.
Chondromyxoid fibroma. Lobular architecture. In addition to myxoid areas, areas with more hyaline cartilaginous matrix can be seen in a subset of cases.
Chondromyxoid fibroma of the ilium. Note the yellowish-grey, relatively uniform lesion, with sharply demarcated borders and expansion of the bone.
Chondromyxoid fibroma. Focal coarse calcification.

Q: Histologically, the characteristic cells of Chondromyxoid Fibroma are stellate or spindle-shaped with eosinophilic processes, and the hypercellular areas often contain admixed [...].
Chondromyxoid fibroma. Stellate cells embedded in a myxoid matrix are seen on the right, with more-cellular areas containing round cells and multinucleated giant cells on the left.
Chondromyxoid fibroma. Moderate nuclear enlargement may be present. The eosinophilic cytoplasmic processes are evident.
A: multinucleated giant cells
Back Extra: Chondromyxoid Fibroma
- Clinical: Pain is the most common symptom, and the lesion is typically a well-demarcated, oval-shaped, lobulated osteolytic, eccentric, and metaphyseally located lesion, with attenuation and expansion of the cortex.
- Micro: Lobules demonstrate hypocellular centres with hypercellular peripheries, and stellate or spindle-shaped cells in a myxoid background. Calcification, when present, is usually coarse.
- Ancillary: Molecular analysis can identify upregulation of GRM1 expression, a specific diagnostic adjunct in distinguishing this entity from its mimics.
Reference Gallery:
Chondromyxoid fibroma. Radiograph shows an eccentrically localized, expansile mixed osteolytic-sclerotic tumour with a well-defined sclerotic margin in the metaphysis and proximal diaphysis of the tibia. The combination of these morphological characteristics with the location is indicative of chondromyxoid fibroma.
Chondromyxoid fibroma. The myxoid components have a high signal intensity on the T2-weighted fat-suppressed images. Note the reactive high signal surrounding the tumour in the bone marrow and in the periosteum medially.
Chondromyxoid fibroma. Stellate cells embedded in a myxoid matrix are seen on the right, with more-cellular areas containing round cells and multinucleated giant cells on the left.
Chondromyxoid fibroma. Moderate nuclear enlargement may be present. The eosinophilic cytoplasmic processes are evident.
Chondromyxoid fibroma. Lobular architecture. In addition to myxoid areas, areas with more hyaline cartilaginous matrix can be seen in a subset of cases.
Chondromyxoid fibroma of the ilium. Note the yellowish-grey, relatively uniform lesion, with sharply demarcated borders and expansion of the bone.
Chondromyxoid fibroma. Focal coarse calcification.

Q: Radiographically, an Enchondroma classically presents with [...] calcifications and frequently involves the short tubular bones of the hands and feet.
Enchondroma. Note the popcorn-like calcifications.
Enchondroma. Symptomatic enchondromas in small tubular bones frequently present with pathological fractures. Note cortical attenuation (white arrow) and fracture (black arrow) in this expansile enchondroma, extending proximally.
A: popcorn-like
Back Extra: Enchondroma
- Clinical: Enchondromas are most commonly found in the short tubular bones of the hands and feet, and are usually asymptomatic. However, they can present with pain, palpable swelling, and pathological fractures in the affected bones.
- Micro: Histologically, enchondromas are hypocellular with an abundance of hyaline cartilage matrix. Tumour cells are embedded within sharp-edged lacunar spaces, and the nuclei are typically small and round with condensed chromatin.
- Ancillary: Immunohistochemistry is usually not helpful; tumour cells are positive for S100. Approximately 24% are positive for the p.Arg132His mutation-specific IDH1 antibody.
Reference Gallery:
Enchondroma. Enchondroma showing encasement: the separate nodules are surrounded by bone, which is a sign of slow growth.
Enchondroma. Note the popcorn-like calcifications.
Enchondroma. CT of a femoral enchondroma illustrates the dense, solid calcifications.
Enchondroma. Symptomatic enchondromas in small tubular bones frequently present with pathological fractures. Note cortical attenuation (white arrow) and fracture (black arrow) in this expansile enchondroma, extending proximally.
Enchondroma. The chondrocytes are typically situated within sharp-edged lacunar spaces. The cytoplasm is frequently retracted to form vacuoles and spider-like eosinophilic extensions. Nuclei are small, round, and hyperchromatic, although larger, vesicular nuclei can also be present. Mitotic figures are usually non-existent and binucleation is uncommon. Finely stippled calcifications within the hyaline matrix are common.
Enchondroma. Enchondromas commonly have a multinodular architectural pattern characterized by islands of cartilage encased by thin mantles of bone that are often separated by marrow. This pattern is more common in larger tumours. Enchondromas in small tubular bones tend to have a more confluent architecture.
Enchondroma. Some enchondromas become heavily calcified, as shown by densely stippled and solid areas of deeply basophilic staining. The chondrocytes are often necrotic in these areas, reduced to eosinophilic bodies within lacunae.

Q: Histologically, an Enchondroma features a hypocellular hyaline cartilage matrix with small, round chondrocytes situated within characteristic [...].
Enchondroma. The chondrocytes are typically situated within sharp-edged lacunar spaces. The cytoplasm is frequently retracted to form vacuoles and spider-like eosinophilic extensions. Nuclei are small, round, and hyperchromatic, although larger, vesicular nuclei can also be present. Mitotic figures are usually non-existent and binucleation is uncommon. Finely stippled calcifications within the hyaline matrix are common.
A: sharp-edged lacunar spaces
Back Extra: Enchondroma
- Clinical: Enchondromas are most commonly found in the short tubular bones of the hands and feet, and are usually asymptomatic. However, they can present with pain, palpable swelling, and pathological fractures in the affected bones.
- Micro: Histologically, enchondromas are hypocellular with an abundance of hyaline cartilage matrix. Tumour cells are embedded within sharp-edged lacunar spaces, and the nuclei are typically small and round with condensed chromatin.
- Ancillary: Immunohistochemistry is usually not helpful; tumour cells are positive for S100. Approximately 24% are positive for the p.Arg132His mutation-specific IDH1 antibody.
Reference Gallery:
Enchondroma. Enchondroma showing encasement: the separate nodules are surrounded by bone, which is a sign of slow growth.
Enchondroma. Note the popcorn-like calcifications.
Enchondroma. CT of a femoral enchondroma illustrates the dense, solid calcifications.
Enchondroma. Symptomatic enchondromas in small tubular bones frequently present with pathological fractures. Note cortical attenuation (white arrow) and fracture (black arrow) in this expansile enchondroma, extending proximally.
Enchondroma. The chondrocytes are typically situated within sharp-edged lacunar spaces. The cytoplasm is frequently retracted to form vacuoles and spider-like eosinophilic extensions. Nuclei are small, round, and hyperchromatic, although larger, vesicular nuclei can also be present. Mitotic figures are usually non-existent and binucleation is uncommon. Finely stippled calcifications within the hyaline matrix are common.
Enchondroma. Enchondromas commonly have a multinodular architectural pattern characterized by islands of cartilage encased by thin mantles of bone that are often separated by marrow. This pattern is more common in larger tumours. Enchondromas in small tubular bones tend to have a more confluent architecture.
Enchondroma. Some enchondromas become heavily calcified, as shown by densely stippled and solid areas of deeply basophilic staining. The chondrocytes are often necrotic in these areas, reduced to eosinophilic bodies within lacunae.

Q: A classic architectural feature of larger Enchondroma tumors is a multinodular pattern of cartilage islands completely surrounded by thin mantles of bone, a sign of slow growth known as [...].
Enchondroma. Enchondroma showing encasement: the separate nodules are surrounded by bone, which is a sign of slow growth.
Enchondroma. Enchondromas commonly have a multinodular architectural pattern characterized by islands of cartilage encased by thin mantles of bone that are often separated by marrow. This pattern is more common in larger tumours. Enchondromas in small tubular bones tend to have a more confluent architecture.
A: encasement
Back Extra: Enchondroma
- Clinical: Enchondromas are most commonly found in the short tubular bones of the hands and feet, and are usually asymptomatic. However, they can present with pain, palpable swelling, and pathological fractures in the affected bones.
- Micro: Histologically, enchondromas are hypocellular with an abundance of hyaline cartilage matrix. Tumour cells are embedded within sharp-edged lacunar spaces, and the nuclei are typically small and round with condensed chromatin.
- Ancillary: Immunohistochemistry is usually not helpful; tumour cells are positive for S100. Approximately 24% are positive for the p.Arg132His mutation-specific IDH1 antibody.
Reference Gallery:
Enchondroma. Enchondroma showing encasement: the separate nodules are surrounded by bone, which is a sign of slow growth.
Enchondroma. Note the popcorn-like calcifications.
Enchondroma. CT of a femoral enchondroma illustrates the dense, solid calcifications.
Enchondroma. Symptomatic enchondromas in small tubular bones frequently present with pathological fractures. Note cortical attenuation (white arrow) and fracture (black arrow) in this expansile enchondroma, extending proximally.
Enchondroma. The chondrocytes are typically situated within sharp-edged lacunar spaces. The cytoplasm is frequently retracted to form vacuoles and spider-like eosinophilic extensions. Nuclei are small, round, and hyperchromatic, although larger, vesicular nuclei can also be present. Mitotic figures are usually non-existent and binucleation is uncommon. Finely stippled calcifications within the hyaline matrix are common.
Enchondroma. Enchondromas commonly have a multinodular architectural pattern characterized by islands of cartilage encased by thin mantles of bone that are often separated by marrow. This pattern is more common in larger tumours. Enchondromas in small tubular bones tend to have a more confluent architecture.
Enchondroma. Some enchondromas become heavily calcified, as shown by densely stippled and solid areas of deeply basophilic staining. The chondrocytes are often necrotic in these areas, reduced to eosinophilic bodies within lacunae.

Q: The most common subtype of Enchondromatosis is [...], which presents with multiple enchondromas causing severe bone deformities (often with unilateral predominance), but notably lacks vascular lesions.
Ollier disease. Conventional radiographs of a child. A,B Progression in lower extremity deformity over time. C The deformity of the hand caused by multiple enchondromas.
A: Ollier disease
Back Extra: Enchondromatosis
- Clinical: Ollier disease and Maffucci syndrome are the most common subtypes of enchondromatosis, characterized by multiple enchondromas and, in Maffucci syndrome, additional cavernous hemangiomas.
- Micro: Enchondromas are well-circumscribed nodules with hypercellular cartilage and enlarged, irregular nuclei. In Ollier disease and Maffucci syndrome, increased cellularity and some nuclear atypia are not sufficient for diagnosing chondrosarcoma.
- Ancillary: Mutations in IDH1 and IDH2 are common in enchondromas and chondrosarcomas. Ollier disease often involves mutations at the p.Arg132 position in exon 4 of IDH1.
Reference Gallery:
Ollier disease. Conventional radiographs of a child. A,B Progression in lower extremity deformity over time. C The deformity of the hand caused by multiple enchondromas.
Maffucci syndrome. A Hand deformity due to multiple enchondromas; note the superficial haemangioma. B In another patient, multiple enchondromas with and without soft tissue extension in the second to fifth digits and the fifth metacarpal bone. In addition, phleboliths (arrows) can be seen in the soft tissue at the bases of the second and fourth fingers, indicating haemangiomas.
Ollier disease. A Tc-99m bone scintigraphy demonstrates unilateral occurrence with deformity of the right lower limb, showing multiple areas of focally increased uptake of the tracer in the femur and tibia. B Anteroposterior radiograph of the right knee and lower leg of the same patient shows structural changes in the marrow cavity and cortical bone of the femur and tibia, consisting of osteolysis and osteosclerosis. C In the proximal tibia, areas with mineralization (calcifications) can be appreciated (arrow). D Coronal fat-suppressed T1-weighted MRI of the femur after intravenous administration of contrast shows multiple partially lobulated areas with increased signal intensity due to enhancement of the chondromatous lesions. There is a large lesion in the distal diaphysis of the femur suggestive of chondrosarcoma (arrow). The enhancement demonstrates rings and arcs (also known as septal or nodular enhancement) consistent with the chondromatous nature of the lesion.

Q: The Maffucci syndrome subtype of Enchondromatosis is uniquely characterized by multiple enchondromas accompanied by soft tissue cavernous [...] (which may calcify to form phleboliths on radiographs).
Maffucci syndrome. A Hand deformity due to multiple enchondromas; note the superficial haemangioma. B In another patient, multiple enchondromas with and without soft tissue extension in the second to fifth digits and the fifth metacarpal bone. In addition, phleboliths (arrows) can be seen in the soft tissue at the bases of the second and fourth fingers, indicating haemangiomas.
A: hemangiomas
Back Extra: Enchondromatosis
- Clinical: Ollier disease and Maffucci syndrome are the most common subtypes of enchondromatosis, characterized by multiple enchondromas and, in Maffucci syndrome, additional cavernous hemangiomas.
- Micro: Enchondromas are well-circumscribed nodules with hypercellular cartilage and enlarged, irregular nuclei. In Ollier disease and Maffucci syndrome, increased cellularity and some nuclear atypia are not sufficient for diagnosing chondrosarcoma.
- Ancillary: Mutations in IDH1 and IDH2 are common in enchondromas and chondrosarcomas. Ollier disease often involves mutations at the p.Arg132 position in exon 4 of IDH1.
Reference Gallery:
Ollier disease. Conventional radiographs of a child. A,B Progression in lower extremity deformity over time. C The deformity of the hand caused by multiple enchondromas.
Maffucci syndrome. A Hand deformity due to multiple enchondromas; note the superficial haemangioma. B In another patient, multiple enchondromas with and without soft tissue extension in the second to fifth digits and the fifth metacarpal bone. In addition, phleboliths (arrows) can be seen in the soft tissue at the bases of the second and fourth fingers, indicating haemangiomas.
Ollier disease. A Tc-99m bone scintigraphy demonstrates unilateral occurrence with deformity of the right lower limb, showing multiple areas of focally increased uptake of the tracer in the femur and tibia. B Anteroposterior radiograph of the right knee and lower leg of the same patient shows structural changes in the marrow cavity and cortical bone of the femur and tibia, consisting of osteolysis and osteosclerosis. C In the proximal tibia, areas with mineralization (calcifications) can be appreciated (arrow). D Coronal fat-suppressed T1-weighted MRI of the femur after intravenous administration of contrast shows multiple partially lobulated areas with increased signal intensity due to enhancement of the chondromatous lesions. There is a large lesion in the distal diaphysis of the femur suggestive of chondrosarcoma (arrow). The enhancement demonstrates rings and arcs (also known as septal or nodular enhancement) consistent with the chondromatous nature of the lesion.

Q: Patients with Enchondromatosis have a significantly increased risk of their lesions undergoing malignant transformation into [...], which may be suspected on MRI if a mass demonstrates rapid growth or cortical destruction.
Ollier disease. A Tc-99m bone scintigraphy demonstrates unilateral occurrence with deformity of the right lower limb, showing multiple areas of focally increased uptake of the tracer in the femur and tibia. B Anteroposterior radiograph of the right knee and lower leg of the same patient shows structural changes in the marrow cavity and cortical bone of the femur and tibia, consisting of osteolysis and osteosclerosis. C In the proximal tibia, areas with mineralization (calcifications) can be appreciated (arrow). D Coronal fat-suppressed T1-weighted MRI of the femur after intravenous administration of contrast shows multiple partially lobulated areas with increased signal intensity due to enhancement of the chondromatous lesions. There is a large lesion in the distal diaphysis of the femur suggestive of chondrosarcoma (arrow). The enhancement demonstrates rings and arcs (also known as septal or nodular enhancement) consistent with the chondromatous nature of the lesion.
A: chondrosarcoma
Back Extra: Enchondromatosis
- Clinical: Ollier disease and Maffucci syndrome are the most common subtypes of enchondromatosis, characterized by multiple enchondromas and, in Maffucci syndrome, additional cavernous hemangiomas.
- Micro: Enchondromas are well-circumscribed nodules with hypercellular cartilage and enlarged, irregular nuclei. In Ollier disease and Maffucci syndrome, increased cellularity and some nuclear atypia are not sufficient for diagnosing chondrosarcoma.
- Ancillary: Mutations in IDH1 and IDH2 are common in enchondromas and chondrosarcomas. Ollier disease often involves mutations at the p.Arg132 position in exon 4 of IDH1.
Reference Gallery:
Ollier disease. Conventional radiographs of a child. A,B Progression in lower extremity deformity over time. C The deformity of the hand caused by multiple enchondromas.
Maffucci syndrome. A Hand deformity due to multiple enchondromas; note the superficial haemangioma. B In another patient, multiple enchondromas with and without soft tissue extension in the second to fifth digits and the fifth metacarpal bone. In addition, phleboliths (arrows) can be seen in the soft tissue at the bases of the second and fourth fingers, indicating haemangiomas.
Ollier disease. A Tc-99m bone scintigraphy demonstrates unilateral occurrence with deformity of the right lower limb, showing multiple areas of focally increased uptake of the tracer in the femur and tibia. B Anteroposterior radiograph of the right knee and lower leg of the same patient shows structural changes in the marrow cavity and cortical bone of the femur and tibia, consisting of osteolysis and osteosclerosis. C In the proximal tibia, areas with mineralization (calcifications) can be appreciated (arrow). D Coronal fat-suppressed T1-weighted MRI of the femur after intravenous administration of contrast shows multiple partially lobulated areas with increased signal intensity due to enhancement of the chondromatous lesions. There is a large lesion in the distal diaphysis of the femur suggestive of chondrosarcoma (arrow). The enhancement demonstrates rings and arcs (also known as septal or nodular enhancement) consistent with the chondromatous nature of the lesion.

Q: Microscopically, an Osteochondroma characteristically exhibits three distinct layers—perichondrium, cartilaginous cap, and bony stalk—with the cap resembling a disorganized growth plate that undergoes [...].
Osteochondroma. From left to right, the three layers can be recognized: perichondrium, cartilaginous cap, and bony stalk, with enchondral ossification at the interface between cartilage and bone. Note the resemblance to the growth plate with organization of hypertrophic chondrocytes in columns.
Osteochondroma. Endochondral ossification occurs at the bone–cartilage interface. There are columns of proliferative chondrocytes surrounded by cartilaginous hyaline matrix, resembling the normal growth plate.
A: endochondral ossification
Back Extra: Osteochondroma
- Clinical: Osteochondromas are often asymptomatic and found incidentally, but symptoms can include a hard, longstanding mass, bursa formation, arthritis, and impingement on adjacent structures.
- Micro: Osteochondromas have three layers: perichondrium, cartilaginous cap, and bony stalk. The cartilage cap resembles disorganized growth plate cartilage with endochondral ossification.
- Ancillary: Chromosomal aberrations involve the EXT1 gene on 8q22-q24.1 or the EXT2 gene on 11p11.2, but molecular testing is not typically required for diagnosis.
Reference Gallery:
Osteochondroma. From left to right, the three layers can be recognized: perichondrium, cartilaginous cap, and bony stalk, with enchondral ossification at the interface between cartilage and bone. Note the resemblance to the growth plate with organization of hypertrophic chondrocytes in columns.
Osteochondroma. Low-power view of osteochondroma.
Osteochondroma. Axial CT of an osteochondroma demonstrating continuity of both the stalk and centre of the lesion with the tibial cortex and medullary cavity, respectively.
Osteochondroma. Macroscopic view showing the external cartilage cap.
Osteochondroma. Cut section revealing the continuity of the cortex and marrow cavity with the underlying bone.
Osteochondroma. The cartilage cap centred by trabecular bone.
Osteochondroma. Endochondral ossification occurs at the bone–cartilage interface. There are columns of proliferative chondrocytes surrounded by cartilaginous hyaline matrix, resembling the normal growth plate.
Osteochondroma formation. A second hit in EXT in a proliferating cell of the growth plate near the bony collar underlies osteochondroma formation in patients with multiple osteochondromas. The cells lose polarity and grow out of the bone through a defective bony collar. In the cartilaginous cap, EXT−/− cells are intermingled with EXT+/− cells (mosaicism). In solitary osteochondromas, two somatic hits are required in a single chondrocyte.

Q: A defining radiologic and macroscopic feature of an Osteochondroma is the direct continuity of the lesion's cortex and [...] with that of the underlying host bone.
Osteochondroma. Axial CT of an osteochondroma demonstrating continuity of both the stalk and centre of the lesion with the tibial cortex and medullary cavity, respectively.
Osteochondroma. Cut section revealing the continuity of the cortex and marrow cavity with the underlying bone.
A: medullary cavity
Back Extra: Osteochondroma
- Clinical: Osteochondromas are often asymptomatic and found incidentally, but symptoms can include a hard, longstanding mass, bursa formation, arthritis, and impingement on adjacent structures.
- Micro: Osteochondromas have three layers: perichondrium, cartilaginous cap, and bony stalk. The cartilage cap resembles disorganized growth plate cartilage with endochondral ossification.
- Ancillary: Chromosomal aberrations involve the EXT1 gene on 8q22-q24.1 or the EXT2 gene on 11p11.2, but molecular testing is not typically required for diagnosis.
Reference Gallery:
Osteochondroma. From left to right, the three layers can be recognized: perichondrium, cartilaginous cap, and bony stalk, with enchondral ossification at the interface between cartilage and bone. Note the resemblance to the growth plate with organization of hypertrophic chondrocytes in columns.
Osteochondroma. Low-power view of osteochondroma.
Osteochondroma. Axial CT of an osteochondroma demonstrating continuity of both the stalk and centre of the lesion with the tibial cortex and medullary cavity, respectively.
Osteochondroma. Macroscopic view showing the external cartilage cap.
Osteochondroma. Cut section revealing the continuity of the cortex and marrow cavity with the underlying bone.
Osteochondroma. The cartilage cap centred by trabecular bone.
Osteochondroma. Endochondral ossification occurs at the bone–cartilage interface. There are columns of proliferative chondrocytes surrounded by cartilaginous hyaline matrix, resembling the normal growth plate.
Osteochondroma formation. A second hit in EXT in a proliferating cell of the growth plate near the bony collar underlies osteochondroma formation in patients with multiple osteochondromas. The cells lose polarity and grow out of the bone through a defective bony collar. In the cartilaginous cap, EXT−/− cells are intermingled with EXT+/− cells (mosaicism). In solitary osteochondromas, two somatic hits are required in a single chondrocyte.

Q: The pathogenesis of both solitary and multiple forms of Osteochondroma is classically driven by inactivating mutations in the [...] genes.
Osteochondroma formation. A second hit in EXT in a proliferating cell of the growth plate near the bony collar underlies osteochondroma formation in patients with multiple osteochondromas. The cells lose polarity and grow out of the bone through a defective bony collar. In the cartilaginous cap, EXT−/− cells are intermingled with EXT+/− cells (mosaicism). In solitary osteochondromas, two somatic hits are required in a single chondrocyte.
A: EXT1 or EXT2
Back Extra: Osteochondroma
- Clinical: Osteochondromas are often asymptomatic and found incidentally, but symptoms can include a hard, longstanding mass, bursa formation, arthritis, and impingement on adjacent structures.
- Micro: Osteochondromas have three layers: perichondrium, cartilaginous cap, and bony stalk. The cartilage cap resembles disorganized growth plate cartilage with endochondral ossification.
- Ancillary: Chromosomal aberrations involve the EXT1 gene on 8q22-q24.1 or the EXT2 gene on 11p11.2, but molecular testing is not typically required for diagnosis.
Reference Gallery:
Osteochondroma. From left to right, the three layers can be recognized: perichondrium, cartilaginous cap, and bony stalk, with enchondral ossification at the interface between cartilage and bone. Note the resemblance to the growth plate with organization of hypertrophic chondrocytes in columns.
Osteochondroma. Low-power view of osteochondroma.
Osteochondroma. Axial CT of an osteochondroma demonstrating continuity of both the stalk and centre of the lesion with the tibial cortex and medullary cavity, respectively.
Osteochondroma. Macroscopic view showing the external cartilage cap.
Osteochondroma. Cut section revealing the continuity of the cortex and marrow cavity with the underlying bone.
Osteochondroma. The cartilage cap centred by trabecular bone.
Osteochondroma. Endochondral ossification occurs at the bone–cartilage interface. There are columns of proliferative chondrocytes surrounded by cartilaginous hyaline matrix, resembling the normal growth plate.
Osteochondroma formation. A second hit in EXT in a proliferating cell of the growth plate near the bony collar underlies osteochondroma formation in patients with multiple osteochondromas. The cells lose polarity and grow out of the bone through a defective bony collar. In the cartilaginous cap, EXT−/− cells are intermingled with EXT+/− cells (mosaicism). In solitary osteochondromas, two somatic hits are required in a single chondrocyte.

Q: Osteochondromyxoma often presents as a painless bone tumor and is a characteristic manifestation in patients with [...].
Tibial osteochondromyxoma. The longitudinally sectioned tibia showed a heterogeneous, elongated, oval tumour. Inferiorly, the lesion was demarcated by a zone of haemorrhage (probably biopsy-related). Superiorly, the lesion was poorly delineated. A vague cylindrical zone (arrows) had a cartilaginous appearance and contained a small cyst with mucoid content.
A: Carney complex
Back Extra: Osteochondromyxoma
- Clinical: Osteochondromyxoma often presents as a painless mass, commonly found in patients with Carney complex.
- Micro: Tumour cells are embedded in a clear and basophilic myxoid matrix, with a moderately cellular to hypocellular, loose mesenchyme.
- Ancillary: Immunohistochemistry may show occasional S100 positivity, but no other ancillary studies are clinically relevant.
Reference Gallery:
Tibial osteochondromyxoma. The longitudinally sectioned tibia showed a heterogeneous, elongated, oval tumour. Inferiorly, the lesion was demarcated by a zone of haemorrhage (probably biopsy-related). Superiorly, the lesion was poorly delineated. A vague cylindrical zone (arrows) had a cartilaginous appearance and contained a small cyst with mucoid content.
Osteochondromyxoma. A sheet of tumour cells with overall clear appearance and vague lobular pattern (right) erodes the bony cortex of the tibial lesion. The hypocellular tumour with dilated sinusoids penetrates between narrow reactive bony trabeculae just beneath the periosteum (top).
Osteochondromyxoma. The circumscribed but unencapsulated hypocellular myxochondroid tumour abuts the nasal submucosa.
Osteochondromyxoma. The tumour is composed of a patternless sheet of cells separated by abundant basophilic mucopolysaccharide ground substance.
Osteochondromyxoma. Polygonal, elongated, and stellate-shaped cells are arranged in moderate-sized lobules.
Osteochondromyxoma. Polygonal and bipolar tumour cells in a barely perceptible, weakly basophilic matrix. Nuclei are hyperchromatic as a result of decalcification.
Osteochondromyxoma. Spindle cells and polygonal cells in a loose matrix with round eosinophilic hyaline areas.
Osteochondromyxoma. Osteoid formation present in an area of polygonal cells with lightly eosinophilic cytoplasm. The nuclei are round and regular, with occasional lobulation and grooving (arrows).

Q: The histologic appearance of osteochondromyxoma classically features polygonal to stellate-shaped tumor cells embedded in an abundant clear and basophilic [...] matrix.
Osteochondromyxoma. The tumour is composed of a patternless sheet of cells separated by abundant basophilic mucopolysaccharide ground substance.
Osteochondromyxoma. Polygonal, elongated, and stellate-shaped cells are arranged in moderate-sized lobules.
A: myxoid
Back Extra: Osteochondromyxoma
- Clinical: Osteochondromyxoma often presents as a painless mass, commonly found in patients with Carney complex.
- Micro: Tumour cells are embedded in a clear and basophilic myxoid matrix, with a moderately cellular to hypocellular, loose mesenchyme.
- Ancillary: Immunohistochemistry may show occasional S100 positivity, but no other ancillary studies are clinically relevant.
Reference Gallery:
Tibial osteochondromyxoma. The longitudinally sectioned tibia showed a heterogeneous, elongated, oval tumour. Inferiorly, the lesion was demarcated by a zone of haemorrhage (probably biopsy-related). Superiorly, the lesion was poorly delineated. A vague cylindrical zone (arrows) had a cartilaginous appearance and contained a small cyst with mucoid content.
Osteochondromyxoma. A sheet of tumour cells with overall clear appearance and vague lobular pattern (right) erodes the bony cortex of the tibial lesion. The hypocellular tumour with dilated sinusoids penetrates between narrow reactive bony trabeculae just beneath the periosteum (top).
Osteochondromyxoma. The circumscribed but unencapsulated hypocellular myxochondroid tumour abuts the nasal submucosa.
Osteochondromyxoma. The tumour is composed of a patternless sheet of cells separated by abundant basophilic mucopolysaccharide ground substance.
Osteochondromyxoma. Polygonal, elongated, and stellate-shaped cells are arranged in moderate-sized lobules.
Osteochondromyxoma. Polygonal and bipolar tumour cells in a barely perceptible, weakly basophilic matrix. Nuclei are hyperchromatic as a result of decalcification.
Osteochondromyxoma. Spindle cells and polygonal cells in a loose matrix with round eosinophilic hyaline areas.
Osteochondromyxoma. Osteoid formation present in an area of polygonal cells with lightly eosinophilic cytoplasm. The nuclei are round and regular, with occasional lobulation and grooving (arrows).

Q: In osteochondromyxoma, hypocellular zones of polygonal cells can occasionally produce areas of new bone matrix, recognized histologically as focal [...] formation.
Osteochondromyxoma. Osteoid formation present in an area of polygonal cells with lightly eosinophilic cytoplasm. The nuclei are round and regular, with occasional lobulation and grooving (arrows).
A: osteoid
Back Extra: Osteochondromyxoma
- Clinical: Osteochondromyxoma often presents as a painless mass, commonly found in patients with Carney complex.
- Micro: Tumour cells are embedded in a clear and basophilic myxoid matrix, with a moderately cellular to hypocellular, loose mesenchyme.
- Ancillary: Immunohistochemistry may show occasional S100 positivity, but no other ancillary studies are clinically relevant.
Reference Gallery:
Tibial osteochondromyxoma. The longitudinally sectioned tibia showed a heterogeneous, elongated, oval tumour. Inferiorly, the lesion was demarcated by a zone of haemorrhage (probably biopsy-related). Superiorly, the lesion was poorly delineated. A vague cylindrical zone (arrows) had a cartilaginous appearance and contained a small cyst with mucoid content.
Osteochondromyxoma. A sheet of tumour cells with overall clear appearance and vague lobular pattern (right) erodes the bony cortex of the tibial lesion. The hypocellular tumour with dilated sinusoids penetrates between narrow reactive bony trabeculae just beneath the periosteum (top).
Osteochondromyxoma. The circumscribed but unencapsulated hypocellular myxochondroid tumour abuts the nasal submucosa.
Osteochondromyxoma. The tumour is composed of a patternless sheet of cells separated by abundant basophilic mucopolysaccharide ground substance.
Osteochondromyxoma. Polygonal, elongated, and stellate-shaped cells are arranged in moderate-sized lobules.
Osteochondromyxoma. Polygonal and bipolar tumour cells in a barely perceptible, weakly basophilic matrix. Nuclei are hyperchromatic as a result of decalcification.
Osteochondromyxoma. Spindle cells and polygonal cells in a loose matrix with round eosinophilic hyaline areas.
Osteochondromyxoma. Osteoid formation present in an area of polygonal cells with lightly eosinophilic cytoplasm. The nuclei are round and regular, with occasional lobulation and grooving (arrows).

Q: Histologically and radiographically, a classic finding at the peripheral margins of a Periosteal Chondroma is the presence of reactive [...].
Periosteal chondroma. CT of a periosteal chondroma of the posterior femur illustrates characteristic radiographic findings. The tumour is well demarcated, partially mineralized, and contained by a discontinuous thin layer of periosteal bone. The underlying cortex is thickened and sclerotic and there is peripheral buttressing around the base of the tumour.
Periosteal chondroma. Low-power micrograph illustrating the classic features of periosteal chondroma. The tumour is situated beneath the periosteum (small arrows) and erodes the underlying sclerotic cortex. Thick periosteal buttressing is present at the periphery (large arrow).
A: cortical buttressing
Back Extra: Periosteal Chondroma
- Clinical: Periosteal chondroma presents as a small palpable swelling causing pain or local discomfort, especially if close to a joint, and is typically solitary.
- Micro: The tumour is well demarcated, lobulated, and composed of bland chondrocytes, often with a thick periosteal layer and cortical buttressing.
- Ancillary: Periosteal chondromas frequently harbour heterozygous mutations in IDH1, with p.Arg132Cys being the most common mutation.
Reference Gallery:
Periosteal chondroma. The tumour is arranged in hyaline lobules composed of bland chondrocytes. Note the thick periosteal layer on top, covering the tumour.
Periosteal chondroma. Classic features of periosteal chondroma. Note the cortical buttressing.
Periosteal chondroma. Well-marginated surface cartilaginous tumour. Note the hyaline, lobulated appearance and the cortical buttressing (arrow), but no invasion.
Periosteal chondroma. CT of a periosteal chondroma of the posterior femur illustrates characteristic radiographic findings. The tumour is well demarcated, partially mineralized, and contained by a discontinuous thin layer of periosteal bone. The underlying cortex is thickened and sclerotic and there is peripheral buttressing around the base of the tumour.
Periosteal chondroma. This radiograph depicts a mineralized tumour (arrow) with underlying cortical sclerosis.
Periosteal chondroma. Low-power micrograph illustrating the classic features of periosteal chondroma. The tumour is situated beneath the periosteum (small arrows) and erodes the underlying sclerotic cortex. Thick periosteal buttressing is present at the periphery (large arrow).

Q: Microscopically, a Periosteal Chondroma forms hyaline lobules of bland chondrocytes that are characteristically covered on the outer surface by a thick [...] layer.
Periosteal chondroma. The tumour is arranged in hyaline lobules composed of bland chondrocytes. Note the thick periosteal layer on top, covering the tumour.
A: periosteal
Back Extra: Periosteal Chondroma
- Clinical: Periosteal chondroma presents as a small palpable swelling causing pain or local discomfort, especially if close to a joint, and is typically solitary.
- Micro: The tumour is well demarcated, lobulated, and composed of bland chondrocytes, often with a thick periosteal layer and cortical buttressing.
- Ancillary: Periosteal chondromas frequently harbour heterozygous mutations in IDH1, with p.Arg132Cys being the most common mutation.
Reference Gallery:
Periosteal chondroma. The tumour is arranged in hyaline lobules composed of bland chondrocytes. Note the thick periosteal layer on top, covering the tumour.
Periosteal chondroma. Classic features of periosteal chondroma. Note the cortical buttressing.
Periosteal chondroma. Well-marginated surface cartilaginous tumour. Note the hyaline, lobulated appearance and the cortical buttressing (arrow), but no invasion.
Periosteal chondroma. CT of a periosteal chondroma of the posterior femur illustrates characteristic radiographic findings. The tumour is well demarcated, partially mineralized, and contained by a discontinuous thin layer of periosteal bone. The underlying cortex is thickened and sclerotic and there is peripheral buttressing around the base of the tumour.
Periosteal chondroma. This radiograph depicts a mineralized tumour (arrow) with underlying cortical sclerosis.
Periosteal chondroma. Low-power micrograph illustrating the classic features of periosteal chondroma. The tumour is situated beneath the periosteum (small arrows) and erodes the underlying sclerotic cortex. Thick periosteal buttressing is present at the periphery (large arrow).

Q: On radiographs, a Periosteal Chondroma often presents as a well-demarcated, partially mineralized surface tumor that characteristically induces underlying [...].
Periosteal chondroma. This radiograph depicts a mineralized tumour (arrow) with underlying cortical sclerosis.
A: cortical sclerosis
Back Extra: Periosteal Chondroma
- Clinical: Periosteal chondroma presents as a small palpable swelling causing pain or local discomfort, especially if close to a joint, and is typically solitary.
- Micro: The tumour is well demarcated, lobulated, and composed of bland chondrocytes, often with a thick periosteal layer and cortical buttressing.
- Ancillary: Periosteal chondromas frequently harbour heterozygous mutations in IDH1, with p.Arg132Cys being the most common mutation.
Reference Gallery:
Periosteal chondroma. The tumour is arranged in hyaline lobules composed of bland chondrocytes. Note the thick periosteal layer on top, covering the tumour.
Periosteal chondroma. Classic features of periosteal chondroma. Note the cortical buttressing.
Periosteal chondroma. Well-marginated surface cartilaginous tumour. Note the hyaline, lobulated appearance and the cortical buttressing (arrow), but no invasion.
Periosteal chondroma. CT of a periosteal chondroma of the posterior femur illustrates characteristic radiographic findings. The tumour is well demarcated, partially mineralized, and contained by a discontinuous thin layer of periosteal bone. The underlying cortex is thickened and sclerotic and there is peripheral buttressing around the base of the tumour.
Periosteal chondroma. This radiograph depicts a mineralized tumour (arrow) with underlying cortical sclerosis.
Periosteal chondroma. Low-power micrograph illustrating the classic features of periosteal chondroma. The tumour is situated beneath the periosteum (small arrows) and erodes the underlying sclerotic cortex. Thick periosteal buttressing is present at the periphery (large arrow).

Q: Microscopically, Subungual Exostosis features an osseous stalk covered by a characteristic [...] cap, which can exhibit hypercellularity and blend with a spindle cell proliferation.
Subungual exostosis. Low-power view showing fibrocartilaginous cap and osseous stalk involving the nail bed.
Subungual exostosis. Cartilage can be hypercellular and atypical. Note the fibrous nature of the cartilaginous matrix.
Subungual exostosis. Cartilage can blend with spindle cell proliferation.
A: fibrocartilaginous
Back Extra: Subungual Exostosis
- Clinical: Subungual exostosis often presents in young patients (<18 years) with a painful swelling in the nail bed that can deform the nail plate.
- Micro: The lesion is composed of fibrocartilaginous tissue at the periphery and bone trabeculae in the stalk, with possible hypercellularity and nuclear enlargement in the cartilage.
- Ancillary: Cytogenetic findings consistently show a t(X;6)(q24-q26;q15-q25) translocation, leading to increased expression of IRS4.
Reference Gallery:
Subungual exostosis. Low-power view showing fibrocartilaginous cap and osseous stalk involving the nail bed.
Subungual exostosis. Cartilage can be hypercellular and atypical. Note the fibrous nature of the cartilaginous matrix.
Subungual exostosis. Cartilage can blend with spindle cell proliferation.
Cytogenetic findings of subungual exostosis. Karyogram showing the characteristic t(X;6) that juxtaposes COL12A1 with IRS4. Arrows indicate breakpoints.
Subungual exostosis. A mature osseous mass, with a soft tissue mass surrounding it, is attached on the cortex of the distal phalanx.

Q: Cytogenetic studies of Subungual Exostosis consistently demonstrate a characteristic [...] translocation, leading to the juxtaposition of COL12A1 and increased expression of IRS4.
Cytogenetic findings of subungual exostosis. Karyogram showing the characteristic t(X;6) that juxtaposes COL12A1 with IRS4. Arrows indicate breakpoints.
A: t(X;6)
Back Extra: Subungual Exostosis
- Clinical: Subungual exostosis often presents in young patients (<18 years) with a painful swelling in the nail bed that can deform the nail plate.
- Micro: The lesion is composed of fibrocartilaginous tissue at the periphery and bone trabeculae in the stalk, with possible hypercellularity and nuclear enlargement in the cartilage.
- Ancillary: Cytogenetic findings consistently show a t(X;6)(q24-q26;q15-q25) translocation, leading to increased expression of IRS4.
Reference Gallery:
Subungual exostosis. Low-power view showing fibrocartilaginous cap and osseous stalk involving the nail bed.
Subungual exostosis. Cartilage can be hypercellular and atypical. Note the fibrous nature of the cartilaginous matrix.
Subungual exostosis. Cartilage can blend with spindle cell proliferation.
Cytogenetic findings of subungual exostosis. Karyogram showing the characteristic t(X;6) that juxtaposes COL12A1 with IRS4. Arrows indicate breakpoints.
Subungual exostosis. A mature osseous mass, with a soft tissue mass surrounding it, is attached on the cortex of the distal phalanx.

Q: In Synovial Chondromatosis, histopathology classically shows multiple [...] embedded within the synovium, often demonstrating peripheral ossification.
Synovial chondromatosis. Composed of multiple cartilaginous nodules. The lesions are cellular and the maturity of the ossification of the nodules is variable, from osteoid deposition to mature bone.
Synovial chondromatosis. A low-power view showing multiple cartilaginous nodules embedded in synovium. There is peripheral ossification of the nodules.
A: cartilaginous nodules
Back Extra: Synovial Chondromatosis
- Clinical: Synovial Chondromatosis often presents with pain, swelling, and mechanical symptoms such as locking, crepitus, and reduced range of movement.
- Micro: Histopathology shows multiple cartilaginous nodules embedded in synovium, often with peripheral ossification.
- Ancillary: MRI is useful for detecting synovial thickening, effusions, and bone erosion, with lobulated areas of low signal intensity and T2 hyperintensity.
Reference Gallery:
Synovial chondromatosis. Composed of multiple cartilaginous nodules. The lesions are cellular and the maturity of the ossification of the nodules is variable, from osteoid deposition to mature bone.
Synovial chondromatosis. Clustered chondrocytes in a hyaline matrix with little atypia.
Synovial chondromatosis. A low-power view showing multiple cartilaginous nodules embedded in synovium. There is peripheral ossification of the nodules.
Synovial chondromatosis. Lateral radiograph of the left knee. Lobular mass at the posterior aspect of the knee with extension into the proximal calf. The mass shows diffuse punctate calcification. Small foci of calcification are also visible at the anterior aspect of the knee.

Q: On radiographs, Synovial Chondromatosis typically presents as a lobular joint mass exhibiting diffuse [...].
Synovial chondromatosis. Lateral radiograph of the left knee. Lobular mass at the posterior aspect of the knee with extension into the proximal calf. The mass shows diffuse punctate calcification. Small foci of calcification are also visible at the anterior aspect of the knee.
A: punctate calcification
Back Extra: Synovial Chondromatosis
- Clinical: Synovial Chondromatosis often presents with pain, swelling, and mechanical symptoms such as locking, crepitus, and reduced range of movement.
- Micro: Histopathology shows multiple cartilaginous nodules embedded in synovium, often with peripheral ossification.
- Ancillary: MRI is useful for detecting synovial thickening, effusions, and bone erosion, with lobulated areas of low signal intensity and T2 hyperintensity.
Reference Gallery:
Synovial chondromatosis. Composed of multiple cartilaginous nodules. The lesions are cellular and the maturity of the ossification of the nodules is variable, from osteoid deposition to mature bone.
Synovial chondromatosis. Clustered chondrocytes in a hyaline matrix with little atypia.
Synovial chondromatosis. A low-power view showing multiple cartilaginous nodules embedded in synovium. There is peripheral ossification of the nodules.
Synovial chondromatosis. Lateral radiograph of the left knee. Lobular mass at the posterior aspect of the knee with extension into the proximal calf. The mass shows diffuse punctate calcification. Small foci of calcification are also visible at the anterior aspect of the knee.

Q: Microscopically, the lesions of Synovial Chondromatosis consist of clustered [...] within a hyaline matrix, typically showing little atypia.
Synovial chondromatosis. Clustered chondrocytes in a hyaline matrix with little atypia.
A: chondrocytes
Back Extra: Synovial Chondromatosis
- Clinical: Synovial Chondromatosis often presents with pain, swelling, and mechanical symptoms such as locking, crepitus, and reduced range of movement.
- Micro: Histopathology shows multiple cartilaginous nodules embedded in synovium, often with peripheral ossification.
- Ancillary: MRI is useful for detecting synovial thickening, effusions, and bone erosion, with lobulated areas of low signal intensity and T2 hyperintensity.
Reference Gallery:
Synovial chondromatosis. Composed of multiple cartilaginous nodules. The lesions are cellular and the maturity of the ossification of the nodules is variable, from osteoid deposition to mature bone.
Synovial chondromatosis. Clustered chondrocytes in a hyaline matrix with little atypia.
Synovial chondromatosis. A low-power view showing multiple cartilaginous nodules embedded in synovium. There is peripheral ossification of the nodules.
Synovial chondromatosis. Lateral radiograph of the left knee. Lobular mass at the posterior aspect of the knee with extension into the proximal calf. The mass shows diffuse punctate calcification. Small foci of calcification are also visible at the anterior aspect of the knee.

Q: In Atypical Cartilaginous Tumor / Chondrosarcoma, Grade 1, a key histologic feature that distinguishes it from an enchondroma is the presence of myxoid matrix changes and the [...] of pre-existing lamellar host bone.
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). ACT/CS1 demonstrating entrapment of pre-existing lamellar host bone, as well as myxoid matrix changes. These two criteria distinguish ACT/CS1 from enchondroma.
A: entrapment
Back Extra: Atypical Cartilaginous Tumour / Chondrosarcoma, Grade 1
- Clinical: Central ACT/CS1s can be asymptomatic or present with pain and swelling, and are often found incidentally. Tumours in the skull base can cause neurological symptoms.
- Micro: ACT/CS1s have a lobulated growth pattern with abundant hyaline cartilaginous matrix, low-to-moderate cellularity, and the presence of binucleated cells but no mitoses.
- Ancillary: IDH1 and IDH2 hotspot mutations are common in ACT/CS1, with about 50% of primary cases and 78% of cases in enchondromatosis having these mutations.
Reference Gallery:
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). ACT/CS1 showing a lobular growth pattern, abundance of predominantly hyaline cartilaginous matrix, and low cellularity.
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). ACT/CS1 demonstrating entrapment of pre-existing lamellar host bone, as well as myxoid matrix changes. These two criteria distinguish ACT/CS1 from enchondroma.
Atypical cartilaginous tumour in long bone. Conventional radiograph of atypical cartilaginous tumour in long bone shows features identical to those of enchondroma, including popcorn-like calcifications.
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). Tumours show moderate cellularity, with cells embedded in hyaline cartilaginous matrix. Nuclei usually show condensed chromatin. Note the presence of binucleated cells, whereas mitoses are absent.

Q: On conventional radiographs, an Atypical Cartilaginous Tumor / Chondrosarcoma, Grade 1 often presents with characteristic [...] calcifications, a radiologic appearance that is identical to an enchondroma.
Atypical cartilaginous tumour in long bone. Conventional radiograph of atypical cartilaginous tumour in long bone shows features identical to those of enchondroma, including popcorn-like calcifications.
A: popcorn-like
Back Extra: Atypical Cartilaginous Tumour / Chondrosarcoma, Grade 1
- Clinical: Central ACT/CS1s can be asymptomatic or present with pain and swelling, and are often found incidentally. Tumours in the skull base can cause neurological symptoms.
- Micro: ACT/CS1s have a lobulated growth pattern with abundant hyaline cartilaginous matrix, low-to-moderate cellularity, and the presence of binucleated cells but no mitoses.
- Ancillary: IDH1 and IDH2 hotspot mutations are common in ACT/CS1, with about 50% of primary cases and 78% of cases in enchondromatosis having these mutations.
Reference Gallery:
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). ACT/CS1 showing a lobular growth pattern, abundance of predominantly hyaline cartilaginous matrix, and low cellularity.
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). ACT/CS1 demonstrating entrapment of pre-existing lamellar host bone, as well as myxoid matrix changes. These two criteria distinguish ACT/CS1 from enchondroma.
Atypical cartilaginous tumour in long bone. Conventional radiograph of atypical cartilaginous tumour in long bone shows features identical to those of enchondroma, including popcorn-like calcifications.
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). Tumours show moderate cellularity, with cells embedded in hyaline cartilaginous matrix. Nuclei usually show condensed chromatin. Note the presence of binucleated cells, whereas mitoses are absent.

Q: Cytologically, an Atypical Cartilaginous Tumor / Chondrosarcoma, Grade 1 displays low-to-moderate cellularity within a hyaline matrix, characteristically lacking mitoses but frequently demonstrating atypia such as [...] cells.
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). ACT/CS1 showing a lobular growth pattern, abundance of predominantly hyaline cartilaginous matrix, and low cellularity.
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). Tumours show moderate cellularity, with cells embedded in hyaline cartilaginous matrix. Nuclei usually show condensed chromatin. Note the presence of binucleated cells, whereas mitoses are absent.
A: binucleated
Back Extra: Atypical Cartilaginous Tumour / Chondrosarcoma, Grade 1
- Clinical: Central ACT/CS1s can be asymptomatic or present with pain and swelling, and are often found incidentally. Tumours in the skull base can cause neurological symptoms.
- Micro: ACT/CS1s have a lobulated growth pattern with abundant hyaline cartilaginous matrix, low-to-moderate cellularity, and the presence of binucleated cells but no mitoses.
- Ancillary: IDH1 and IDH2 hotspot mutations are common in ACT/CS1, with about 50% of primary cases and 78% of cases in enchondromatosis having these mutations.
Reference Gallery:
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). ACT/CS1 showing a lobular growth pattern, abundance of predominantly hyaline cartilaginous matrix, and low cellularity.
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). ACT/CS1 demonstrating entrapment of pre-existing lamellar host bone, as well as myxoid matrix changes. These two criteria distinguish ACT/CS1 from enchondroma.
Atypical cartilaginous tumour in long bone. Conventional radiograph of atypical cartilaginous tumour in long bone shows features identical to those of enchondroma, including popcorn-like calcifications.
Atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). Tumours show moderate cellularity, with cells embedded in hyaline cartilaginous matrix. Nuclei usually show condensed chromatin. Note the presence of binucleated cells, whereas mitoses are absent.

Q: Histologically, Clear Cell Chondrosarcoma is characterized by lobules of round to polygonal cells with abundant clear to eosinophilic cytoplasm admixed with trabeculae of [...].
Clear cell chondrosarcoma. Round or polygonal cells with slightly eosinophilic cytoplasm are arranged in lobules and sheets, admixed with trabeculae of woven bone.
Clear cell chondrosarcoma. High-power view of clear cell chondrosarcoma; note the abundant cytoplasm, with the centrally placed nucleus with central nucleolus.
A: woven bone
Back Extra: Clear Cell Chondrosarcoma
- Clinical: Pain is the most common presenting symptom in patients with clear cell chondrosarcoma, often lasting over a year.
- Micro: Clear cell chondrosarcoma is characterized by lobules of cells with abundant clear or slightly eosinophilic cytoplasm, large round nuclei, and rare mitotic figures.
- Ancillary: Immunohistochemically, clear cell chondrosarcoma cells stain strongly for S100 and occasionally for cytokeratins (AE1/AE3 and CK18).
Reference Gallery:
Clear cell chondrosarcoma. Plain radiography shows a well-defined lytic lesion with calcification in the femoral head and neck.
Clear cell chondrosarcoma. Coronal reformatted CT highlights the intramedullary tumour with spotty mineralization.
Clear cell chondrosarcoma. Low-power view of the transition to low-grade clear cell chondrosarcomatous areas.
Clear cell chondrosarcoma. Round or polygonal cells with slightly eosinophilic cytoplasm are arranged in lobules and sheets, admixed with trabeculae of woven bone.
Clear cell chondrosarcoma. Tumour cells stain strongly with antibodies against S100.
Clear cell chondrosarcoma. Tumour cells focally show positivity for pancytokeratin AE1/AE3.
Clear cell chondrosarcoma. High-power view of clear cell chondrosarcoma; note the abundant cytoplasm, with the centrally placed nucleus with central nucleolus.

Q: Immunohistochemically, Clear Cell Chondrosarcoma tumor cells demonstrate strong positivity for S100 and focal, potentially misleading positivity for [...] (e.g., AE1/AE3).
Clear cell chondrosarcoma. Tumour cells stain strongly with antibodies against S100.
Clear cell chondrosarcoma. Tumour cells focally show positivity for pancytokeratin AE1/AE3.
A: cytokeratins
Back Extra: Clear Cell Chondrosarcoma
- Clinical: Pain is the most common presenting symptom in patients with clear cell chondrosarcoma, often lasting over a year.
- Micro: Clear cell chondrosarcoma is characterized by lobules of cells with abundant clear or slightly eosinophilic cytoplasm, large round nuclei, and rare mitotic figures.
- Ancillary: Immunohistochemically, clear cell chondrosarcoma cells stain strongly for S100 and occasionally for cytokeratins (AE1/AE3 and CK18).
Reference Gallery:
Clear cell chondrosarcoma. Plain radiography shows a well-defined lytic lesion with calcification in the femoral head and neck.
Clear cell chondrosarcoma. Coronal reformatted CT highlights the intramedullary tumour with spotty mineralization.
Clear cell chondrosarcoma. Low-power view of the transition to low-grade clear cell chondrosarcomatous areas.
Clear cell chondrosarcoma. Round or polygonal cells with slightly eosinophilic cytoplasm are arranged in lobules and sheets, admixed with trabeculae of woven bone.
Clear cell chondrosarcoma. Tumour cells stain strongly with antibodies against S100.
Clear cell chondrosarcoma. Tumour cells focally show positivity for pancytokeratin AE1/AE3.
Clear cell chondrosarcoma. High-power view of clear cell chondrosarcoma; note the abundant cytoplasm, with the centrally placed nucleus with central nucleolus.

Q: Radiographically, Clear Cell Chondrosarcoma typically presents as a well-defined lytic intramedullary tumor with spotty mineralization that characteristically involves the epiphysis of the [...].
Clear cell chondrosarcoma. Plain radiography shows a well-defined lytic lesion with calcification in the femoral head and neck.
Clear cell chondrosarcoma. Coronal reformatted CT highlights the intramedullary tumour with spotty mineralization.
A: femoral head
Back Extra: Clear Cell Chondrosarcoma
- Clinical: Pain is the most common presenting symptom in patients with clear cell chondrosarcoma, often lasting over a year.
- Micro: Clear cell chondrosarcoma is characterized by lobules of cells with abundant clear or slightly eosinophilic cytoplasm, large round nuclei, and rare mitotic figures.
- Ancillary: Immunohistochemically, clear cell chondrosarcoma cells stain strongly for S100 and occasionally for cytokeratins (AE1/AE3 and CK18).
Reference Gallery:
Clear cell chondrosarcoma. Plain radiography shows a well-defined lytic lesion with calcification in the femoral head and neck.
Clear cell chondrosarcoma. Coronal reformatted CT highlights the intramedullary tumour with spotty mineralization.
Clear cell chondrosarcoma. Low-power view of the transition to low-grade clear cell chondrosarcomatous areas.
Clear cell chondrosarcoma. Round or polygonal cells with slightly eosinophilic cytoplasm are arranged in lobules and sheets, admixed with trabeculae of woven bone.
Clear cell chondrosarcoma. Tumour cells stain strongly with antibodies against S100.
Clear cell chondrosarcoma. Tumour cells focally show positivity for pancytokeratin AE1/AE3.
Clear cell chondrosarcoma. High-power view of clear cell chondrosarcoma; note the abundant cytoplasm, with the centrally placed nucleus with central nucleolus.

Q: Histologically and grossly, dedifferentiated chondrosarcoma is uniquely characterized by an [...] between conventional low-grade hyaline cartilage and a non-cartilaginous high-grade sarcoma.
Dedifferentiated chondrosarcoma. Corresponding resection specimen of the dedifferentiated chondrosarcoma shown in Fig. #6683 and Fig. #6667. The greyish-white hyaline cartilage component fills the medullary cavity, whereas the fleshy, tan and reddish-brown high-grade sarcoma component involves surrounding soft tissue.
Dedifferentiated chondrosarcoma. There is an abrupt transition between the low-grade chondrosarcoma and high-grade sarcoma components.
A: abrupt transition
Back Extra: Dedifferentiated Chondrosarcoma
- Clinical: Dedifferentiated chondrosarcoma commonly presents with pain and a palpable mass, and about 20% of patients have a pathological fracture.
- Micro: There is an abrupt transition between the conventional hyaline cartilage and high-grade sarcoma components in dedifferentiated chondrosarcoma.
- Ancillary: Dedifferentiated chondrosarcomas often harbour mutations in IDH1 or IDH2, and the high-grade component may show p53 overexpression.
Reference Gallery:
Dedifferentiated chondrosarcoma. Sagittal fat-suppressed T2-weighted MRI of the humerus demonstrates imaging features of a high-grade chondrosarcoma. The MRI shows, in the intramedullary portion of the mid- and proximal humeral diaphysis, chondroid matrix with homogeneous high signal, associated expansion, cortical permeation, irregular periosteal reaction, and soft tissue reactive oedema or even tumour extension. More proximally, the more aggressive part of the tumour shows an area with more lytic destruction with an associated pathological fracture and an adjacent soft tissue mass containing amorphous osteoid matrix.
Dedifferentiated chondrosarcoma. Corresponding resection specimen of the dedifferentiated chondrosarcoma shown in Fig. #6683 and Fig. #6667. The greyish-white hyaline cartilage component fills the medullary cavity, whereas the fleshy, tan and reddish-brown high-grade sarcoma component involves surrounding soft tissue.
Dedifferentiated chondrosarcoma. There is an abrupt transition between the low-grade chondrosarcoma and high-grade sarcoma components.
Dedifferentiated chondrosarcoma. The high-grade sarcoma in this dedifferentiated chondrosarcoma shows deposition of osteoid.
Dedifferentiated chondrosarcoma. The high-grade sarcoma in this dedifferentiated chondrosarcoma is undifferentiated pleomorphic sarcoma.
Dedifferentiated chondrosarcoma. Anteroposterior radiograph demonstrates imaging features of a high-grade chondrosarcoma. The radiograph shows, in the intramedullary portion of the mid- and proximal humeral diaphysis, chondroid matrix with homogeneous high signal, associated expansion, cortical permeation, irregular periosteal reaction, and soft tissue reactive oedema or even tumour extension. More proximally, the more aggressive part of the tumour shows an area with more lytic destruction with an associated pathological fracture and an adjacent soft tissue mass containing amorphous osteoid matrix.

Q: Radiographically and clinically, an aggressive complication seen in approximately 20% of patients with dedifferentiated chondrosarcoma is a [...] resulting from extensive lytic bone destruction and adjacent soft tissue tumor extension.
Dedifferentiated chondrosarcoma. Sagittal fat-suppressed T2-weighted MRI of the humerus demonstrates imaging features of a high-grade chondrosarcoma. The MRI shows, in the intramedullary portion of the mid- and proximal humeral diaphysis, chondroid matrix with homogeneous high signal, associated expansion, cortical permeation, irregular periosteal reaction, and soft tissue reactive oedema or even tumour extension. More proximally, the more aggressive part of the tumour shows an area with more lytic destruction with an associated pathological fracture and an adjacent soft tissue mass containing amorphous osteoid matrix.
Dedifferentiated chondrosarcoma. Anteroposterior radiograph demonstrates imaging features of a high-grade chondrosarcoma. The radiograph shows, in the intramedullary portion of the mid- and proximal humeral diaphysis, chondroid matrix with homogeneous high signal, associated expansion, cortical permeation, irregular periosteal reaction, and soft tissue reactive oedema or even tumour extension. More proximally, the more aggressive part of the tumour shows an area with more lytic destruction with an associated pathological fracture and an adjacent soft tissue mass containing amorphous osteoid matrix.
A: pathological fracture
Back Extra: Dedifferentiated Chondrosarcoma
- Clinical: Dedifferentiated chondrosarcoma commonly presents with pain and a palpable mass, and about 20% of patients have a pathological fracture.
- Micro: There is an abrupt transition between the conventional hyaline cartilage and high-grade sarcoma components in dedifferentiated chondrosarcoma.
- Ancillary: Dedifferentiated chondrosarcomas often harbour mutations in IDH1 or IDH2, and the high-grade component may show p53 overexpression.
Reference Gallery:
Dedifferentiated chondrosarcoma. Sagittal fat-suppressed T2-weighted MRI of the humerus demonstrates imaging features of a high-grade chondrosarcoma. The MRI shows, in the intramedullary portion of the mid- and proximal humeral diaphysis, chondroid matrix with homogeneous high signal, associated expansion, cortical permeation, irregular periosteal reaction, and soft tissue reactive oedema or even tumour extension. More proximally, the more aggressive part of the tumour shows an area with more lytic destruction with an associated pathological fracture and an adjacent soft tissue mass containing amorphous osteoid matrix.
Dedifferentiated chondrosarcoma. Corresponding resection specimen of the dedifferentiated chondrosarcoma shown in Fig. #6683 and Fig. #6667. The greyish-white hyaline cartilage component fills the medullary cavity, whereas the fleshy, tan and reddish-brown high-grade sarcoma component involves surrounding soft tissue.
Dedifferentiated chondrosarcoma. There is an abrupt transition between the low-grade chondrosarcoma and high-grade sarcoma components.
Dedifferentiated chondrosarcoma. The high-grade sarcoma in this dedifferentiated chondrosarcoma shows deposition of osteoid.
Dedifferentiated chondrosarcoma. The high-grade sarcoma in this dedifferentiated chondrosarcoma is undifferentiated pleomorphic sarcoma.
Dedifferentiated chondrosarcoma. Anteroposterior radiograph demonstrates imaging features of a high-grade chondrosarcoma. The radiograph shows, in the intramedullary portion of the mid- and proximal humeral diaphysis, chondroid matrix with homogeneous high signal, associated expansion, cortical permeation, irregular periosteal reaction, and soft tissue reactive oedema or even tumour extension. More proximally, the more aggressive part of the tumour shows an area with more lytic destruction with an associated pathological fracture and an adjacent soft tissue mass containing amorphous osteoid matrix.

Q: When a biphasic bone tumor exhibits a low-grade hyaline cartilage component directly juxtaposed against a high-grade sarcoma (which may produce osteoid or resemble an undifferentiated pleomorphic sarcoma), the diagnosis is [...].
Dedifferentiated chondrosarcoma. The high-grade sarcoma in this dedifferentiated chondrosarcoma shows deposition of osteoid.
Dedifferentiated chondrosarcoma. The high-grade sarcoma in this dedifferentiated chondrosarcoma is undifferentiated pleomorphic sarcoma.
A: dedifferentiated chondrosarcoma
Back Extra: Dedifferentiated Chondrosarcoma
- Clinical: Dedifferentiated chondrosarcoma commonly presents with pain and a palpable mass, and about 20% of patients have a pathological fracture.
- Micro: There is an abrupt transition between the conventional hyaline cartilage and high-grade sarcoma components in dedifferentiated chondrosarcoma.
- Ancillary: Dedifferentiated chondrosarcomas often harbour mutations in IDH1 or IDH2, and the high-grade component may show p53 overexpression.
Reference Gallery:
Dedifferentiated chondrosarcoma. Sagittal fat-suppressed T2-weighted MRI of the humerus demonstrates imaging features of a high-grade chondrosarcoma. The MRI shows, in the intramedullary portion of the mid- and proximal humeral diaphysis, chondroid matrix with homogeneous high signal, associated expansion, cortical permeation, irregular periosteal reaction, and soft tissue reactive oedema or even tumour extension. More proximally, the more aggressive part of the tumour shows an area with more lytic destruction with an associated pathological fracture and an adjacent soft tissue mass containing amorphous osteoid matrix.
Dedifferentiated chondrosarcoma. Corresponding resection specimen of the dedifferentiated chondrosarcoma shown in Fig. #6683 and Fig. #6667. The greyish-white hyaline cartilage component fills the medullary cavity, whereas the fleshy, tan and reddish-brown high-grade sarcoma component involves surrounding soft tissue.
Dedifferentiated chondrosarcoma. There is an abrupt transition between the low-grade chondrosarcoma and high-grade sarcoma components.
Dedifferentiated chondrosarcoma. The high-grade sarcoma in this dedifferentiated chondrosarcoma shows deposition of osteoid.
Dedifferentiated chondrosarcoma. The high-grade sarcoma in this dedifferentiated chondrosarcoma is undifferentiated pleomorphic sarcoma.
Dedifferentiated chondrosarcoma. Anteroposterior radiograph demonstrates imaging features of a high-grade chondrosarcoma. The radiograph shows, in the intramedullary portion of the mid- and proximal humeral diaphysis, chondroid matrix with homogeneous high signal, associated expansion, cortical permeation, irregular periosteal reaction, and soft tissue reactive oedema or even tumour extension. More proximally, the more aggressive part of the tumour shows an area with more lytic destruction with an associated pathological fracture and an adjacent soft tissue mass containing amorphous osteoid matrix.

Q: Grossly, a Secondary Peripheral Atypical Cartilaginous Tumour / Chondrosarcoma, Grade 1 often arises juxtaposed to a pre-existing osteochondroma and is suspected when the cartilaginous cap exceeds [...] in thickness.
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1), resection specimen. Secondary peripheral ACT/CS1 arising juxtaposed to a pre-existing osteochondroma. The size of the cartilaginous cap, which should be measured perpendicular to the tidemark, exceeds 2 cm.
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1), resection specimen. Large secondary peripheral ACT/CS1. Note the remnants of the stalk on the right, as well as the abundant nodular proliferation of cartilage, with areas of calcification.
A: 2 cm
Back Extra: Secondary Peripheral Atypical Cartilaginous Tumour / Chondrosarcoma, Grade 1
- Clinical: Patients usually present with a longstanding mass and recent rapid enlargement or pain, especially if the tumour grows after puberty.
- Micro: The tumour shows moderate cellularity with an abundance of hyaline cartilaginous matrix. Coarse and irregular calcifications are prominent.
- Ancillary: The tumour cells strongly express S100, and EXT1 or EXT2 mutations are present in about 40% of the tumour cells.
Reference Gallery:
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1), resection specimen. Secondary peripheral ACT/CS1 arising juxtaposed to a pre-existing osteochondroma. The size of the cartilaginous cap, which should be measured perpendicular to the tidemark, exceeds 2 cm.
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). A lobular hyaline cartilaginous tumour is seen with nodular extension into the surrounding soft tissues.
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). Tumours show moderate cellularity and an abundance of hyaline cartilaginous matrix. Areas of hypertrophic differentiation and calcification (right) can be seen.
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1), resection specimen. Large secondary peripheral ACT/CS1. Note the remnants of the stalk on the right, as well as the abundant nodular proliferation of cartilage, with areas of calcification.

Q: Histologically, Secondary Peripheral Atypical Cartilaginous Tumour / Chondrosarcoma, Grade 1 exhibits moderate cellularity, an abundant hyaline cartilaginous matrix, and often shows nodular extension into the surrounding [...].
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). A lobular hyaline cartilaginous tumour is seen with nodular extension into the surrounding soft tissues.
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). Tumours show moderate cellularity and an abundance of hyaline cartilaginous matrix. Areas of hypertrophic differentiation and calcification (right) can be seen.
A: soft tissues
Back Extra: Secondary Peripheral Atypical Cartilaginous Tumour / Chondrosarcoma, Grade 1
- Clinical: Patients usually present with a longstanding mass and recent rapid enlargement or pain, especially if the tumour grows after puberty.
- Micro: The tumour shows moderate cellularity with an abundance of hyaline cartilaginous matrix. Coarse and irregular calcifications are prominent.
- Ancillary: The tumour cells strongly express S100, and EXT1 or EXT2 mutations are present in about 40% of the tumour cells.
Reference Gallery:
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1), resection specimen. Secondary peripheral ACT/CS1 arising juxtaposed to a pre-existing osteochondroma. The size of the cartilaginous cap, which should be measured perpendicular to the tidemark, exceeds 2 cm.
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). A lobular hyaline cartilaginous tumour is seen with nodular extension into the surrounding soft tissues.
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). Tumours show moderate cellularity and an abundance of hyaline cartilaginous matrix. Areas of hypertrophic differentiation and calcification (right) can be seen.
Secondary peripheral atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1), resection specimen. Large secondary peripheral ACT/CS1. Note the remnants of the stalk on the right, as well as the abundant nodular proliferation of cartilage, with areas of calcification.

Q: Histologically, [...] is a cartilaginous matrix-producing tumor that exhibits increased cellularity, nuclear pleomorphism, and prominent myxoid matrix changes, with the highest grade demonstrating spindled cells and readily identifiable mitoses.
Secondary peripheral chondrosarcoma. Grade 2 chondrosarcoma with increased cellularity and myxoid matrix changes.
Secondary peripheral chondrosarcoma. Grade 3 chondrosarcoma with increased cellularity, myxoid matrix changes, and spindled cells. Mitoses are easily found.
A: Secondary Peripheral Chondrosarcoma, Grades 2 and 3
Back Extra: Secondary Peripheral Chondrosarcoma, Grades 2 and 3
- Clinical: Signs and symptoms include enlargement or pain in a longstanding mass, especially after puberty. Neurological symptoms and limited joint motion can be present.
- Micro: Grade 2 and 3 secondary peripheral chondrosarcomas are lobular cartilaginous matrix–producing tumours with increased cellularity, nuclear pleomorphism, and mitoses.
- Ancillary: These tumours can be positive for S100. Molecular analysis is rarely needed for diagnosis.
Reference Gallery:
Secondary peripheral chondrosarcoma. Grade 2 chondrosarcoma with increased cellularity and myxoid matrix changes.
Secondary peripheral chondrosarcoma. Grade 3 chondrosarcoma with increased cellularity, myxoid matrix changes, and spindled cells. Mitoses are easily found.
Secondary peripheral chondrosarcoma arising in a patient with multiple osteochondromas. Conventional radiograph (left) and surgical specimen (right) of the right proximal fibula. Note the thickness of the cartilaginous cap (> 2 cm), flaring of the cortex (macro), and indistinct margins with irregular mineralization (radiograph).
Secondary peripheral chondrosarcoma arising in a patient with multiple osteochondromas. Discrete peripheral nodules of cartilage are embedded in the soft tissue at the periphery of the lesion. These features explain the irregular margins and the possibility of local recurrence when the lesion is resected with inadequate surgical margins.

Q: In Secondary Peripheral Chondrosarcoma, Grades 2 and 3 arising from multiple osteochondromas, gross and radiographic evaluation typically reveals discrete peripheral soft tissue nodules and a thickened cartilaginous cap measuring greater than [...].
Secondary peripheral chondrosarcoma arising in a patient with multiple osteochondromas. Conventional radiograph (left) and surgical specimen (right) of the right proximal fibula. Note the thickness of the cartilaginous cap (> 2 cm), flaring of the cortex (macro), and indistinct margins with irregular mineralization (radiograph).
Secondary peripheral chondrosarcoma arising in a patient with multiple osteochondromas. Discrete peripheral nodules of cartilage are embedded in the soft tissue at the periphery of the lesion. These features explain the irregular margins and the possibility of local recurrence when the lesion is resected with inadequate surgical margins.
A: 2 cm
Back Extra: Secondary Peripheral Chondrosarcoma, Grades 2 and 3
- Clinical: Signs and symptoms include enlargement or pain in a longstanding mass, especially after puberty. Neurological symptoms and limited joint motion can be present.
- Micro: Grade 2 and 3 secondary peripheral chondrosarcomas are lobular cartilaginous matrix–producing tumours with increased cellularity, nuclear pleomorphism, and mitoses.
- Ancillary: These tumours can be positive for S100. Molecular analysis is rarely needed for diagnosis.
Reference Gallery:
Secondary peripheral chondrosarcoma. Grade 2 chondrosarcoma with increased cellularity and myxoid matrix changes.
Secondary peripheral chondrosarcoma. Grade 3 chondrosarcoma with increased cellularity, myxoid matrix changes, and spindled cells. Mitoses are easily found.
Secondary peripheral chondrosarcoma arising in a patient with multiple osteochondromas. Conventional radiograph (left) and surgical specimen (right) of the right proximal fibula. Note the thickness of the cartilaginous cap (> 2 cm), flaring of the cortex (macro), and indistinct margins with irregular mineralization (radiograph).
Secondary peripheral chondrosarcoma arising in a patient with multiple osteochondromas. Discrete peripheral nodules of cartilage are embedded in the soft tissue at the periphery of the lesion. These features explain the irregular margins and the possibility of local recurrence when the lesion is resected with inadequate surgical margins.

Q: Radiographically and grossly, Central Chondrosarcoma, Grades 2 and 3 typically presents as a large tumor (> 5 cm) featuring ill-defined, [...] lesions, cortical scalloping, and frequent regions of hemorrhage or necrosis.
High-grade central chondrosarcoma. Radiograph showing mainly osteolytic, ill-defined lesion in the proximal femur (arrows). There are small calcifications centrally.
High-grade central chondrosarcoma. Coronal reconstruction of CT showing an osteolytic, ill-defined lesion in the proximal femur (arrows). Tunnelling is depicted in the cortex at the minor trochanter.
High-grade central chondrosarcoma. This tumour involves the proximal femur. Note the haemorrhagic and necrotic areas, and the cortical scalloping.
A: osteolytic
Back Extra: Central Chondrosarcoma, Grades 2 and 3
- Clinical: Central Chondrosarcoma, Grades 2 and 3, typically presents with pain and swelling, and can cause pathological fractures. Tumours are usually > 5 cm with large osteolytic areas on radiographs.
- Micro: High-grade central chondrosarcomas show increased cellularity, myxoid matrix changes, and more nuclear atypia compared to Grade 1. Mitoses are easily seen in Grade 3.
- Ancillary: Grade 2 and 3 central chondrosarcomas often carry IDH1 or IDH2 mutations and are characterized by aneuploidy and complex karyotypes. TP53 is mutated in 20–49% of cases.
Reference Gallery:
High-grade central chondrosarcoma. Radiograph showing mainly osteolytic, ill-defined lesion in the proximal femur (arrows). There are small calcifications centrally.
High-grade central chondrosarcoma. Coronal reconstruction of CT showing an osteolytic, ill-defined lesion in the proximal femur (arrows). Tunnelling is depicted in the cortex at the minor trochanter.
High-grade central chondrosarcoma. Coronal gadolinium chelate–enhanced fat-suppressed MRI. Centrally septonodular enhancement typical for cartilaginous tumour is seen. Apart from size (> 5 cm), there are several features indicating the presence of high-grade chondrosarcoma rather than atypical cartilaginous tumour. In the periphery, enhancement is more homogeneous. Peripheral to the tumour, intraosseous and extraosseous ill-defined reactive changes are enhancing. Also, high signal in cortical bone medially and circumferential periostitis are visualized.
High-grade central chondrosarcoma. Axial gadolinium chelate–enhanced fat-suppressed MRI. Centrally septonodular enhancement typical for cartilaginous tumour is seen. Apart from size (> 5 cm), there are several features indicating the presence of high-grade chondrosarcoma rather than atypical cartilaginous tumour. In the periphery, enhancement is more homogeneous. Peripheral to the tumour, intraosseous and extraosseous ill-defined reactive changes are enhancing. High signal in cortical bone medially and circumferential periostitis are also visualized.
High-grade central chondrosarcoma. Axial T2-weighted fat-suppressed image shows the cortical involvement and the periosteal and soft tissue reactive changes as high signal intensity. The intraosseous tumour component has an inhomogeneous mainly high signal intensity, consistent with mucoid areas (non-enhancing on gadolinium chelate images) and cellular areas (enhancing on gadolinium chelate images).
High-grade central chondrosarcoma. Whole-body maximum intensity projection of FDG PET shows markedly increased FDG uptake in the lesion, consistent with high-grade sarcoma and not atypical cartilaginous tumour.
Central chondrosarcoma. High-grade. A low-power view showing permeative growth pattern, in which the pre-existing bone trabeculae are entrapped by the tumour, filling the marrow cavities.
Central chondrosarcoma. Grade 2. This low-power view demonstrates the typical lobular growth pattern. There are extensive myxoid matrix changes.
Central chondrosarcoma. Grade 2. Cellularity is increased compared with atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). The matrix is hyaline, with focal myxoid changes.
Central chondrosarcoma. Grade 2. This high-power view shows extensive myxoid matrix, increased cellularity, and more nuclear atypia compared with atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1).
Central chondrosarcoma. Grade 3. High cellularity, myxoid matrix changes, and spindle cell changes. Mitoses are easily seen.
High-grade central chondrosarcoma. This tumour involves the proximal femur. Note the haemorrhagic and necrotic areas, and the cortical scalloping.

Q: Histologically, Central Chondrosarcoma, Grades 2 and 3 displays a permeative growth pattern that entraps host bone trabeculae, accompanied by increased cellularity, nuclear atypia, and prominent [...] matrix changes.
Central chondrosarcoma. High-grade. A low-power view showing permeative growth pattern, in which the pre-existing bone trabeculae are entrapped by the tumour, filling the marrow cavities.
Central chondrosarcoma. Grade 2. This low-power view demonstrates the typical lobular growth pattern. There are extensive myxoid matrix changes.
Central chondrosarcoma. Grade 2. This high-power view shows extensive myxoid matrix, increased cellularity, and more nuclear atypia compared with atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1).
A: myxoid
Back Extra: Central Chondrosarcoma, Grades 2 and 3
- Clinical: Central Chondrosarcoma, Grades 2 and 3, typically presents with pain and swelling, and can cause pathological fractures. Tumours are usually > 5 cm with large osteolytic areas on radiographs.
- Micro: High-grade central chondrosarcomas show increased cellularity, myxoid matrix changes, and more nuclear atypia compared to Grade 1. Mitoses are easily seen in Grade 3.
- Ancillary: Grade 2 and 3 central chondrosarcomas often carry IDH1 or IDH2 mutations and are characterized by aneuploidy and complex karyotypes. TP53 is mutated in 20–49% of cases.
Reference Gallery:
High-grade central chondrosarcoma. Radiograph showing mainly osteolytic, ill-defined lesion in the proximal femur (arrows). There are small calcifications centrally.
High-grade central chondrosarcoma. Coronal reconstruction of CT showing an osteolytic, ill-defined lesion in the proximal femur (arrows). Tunnelling is depicted in the cortex at the minor trochanter.
High-grade central chondrosarcoma. Coronal gadolinium chelate–enhanced fat-suppressed MRI. Centrally septonodular enhancement typical for cartilaginous tumour is seen. Apart from size (> 5 cm), there are several features indicating the presence of high-grade chondrosarcoma rather than atypical cartilaginous tumour. In the periphery, enhancement is more homogeneous. Peripheral to the tumour, intraosseous and extraosseous ill-defined reactive changes are enhancing. Also, high signal in cortical bone medially and circumferential periostitis are visualized.
High-grade central chondrosarcoma. Axial gadolinium chelate–enhanced fat-suppressed MRI. Centrally septonodular enhancement typical for cartilaginous tumour is seen. Apart from size (> 5 cm), there are several features indicating the presence of high-grade chondrosarcoma rather than atypical cartilaginous tumour. In the periphery, enhancement is more homogeneous. Peripheral to the tumour, intraosseous and extraosseous ill-defined reactive changes are enhancing. High signal in cortical bone medially and circumferential periostitis are also visualized.
High-grade central chondrosarcoma. Axial T2-weighted fat-suppressed image shows the cortical involvement and the periosteal and soft tissue reactive changes as high signal intensity. The intraosseous tumour component has an inhomogeneous mainly high signal intensity, consistent with mucoid areas (non-enhancing on gadolinium chelate images) and cellular areas (enhancing on gadolinium chelate images).
High-grade central chondrosarcoma. Whole-body maximum intensity projection of FDG PET shows markedly increased FDG uptake in the lesion, consistent with high-grade sarcoma and not atypical cartilaginous tumour.
Central chondrosarcoma. High-grade. A low-power view showing permeative growth pattern, in which the pre-existing bone trabeculae are entrapped by the tumour, filling the marrow cavities.
Central chondrosarcoma. Grade 2. This low-power view demonstrates the typical lobular growth pattern. There are extensive myxoid matrix changes.
Central chondrosarcoma. Grade 2. Cellularity is increased compared with atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1). The matrix is hyaline, with focal myxoid changes.
Central chondrosarcoma. Grade 2. This high-power view shows extensive myxoid matrix, increased cellularity, and more nuclear atypia compared with atypical cartilaginous tumour / chondrosarcoma, grade 1 (ACT/CS1).
Central chondrosarcoma. Grade 3. High cellularity, myxoid matrix changes, and spindle cell changes. Mitoses are easily seen.
High-grade central chondrosarcoma. This tumour involves the proximal femur. Note the haemorrhagic and necrotic areas, and the cortical scalloping.

Q: The classic histologic hallmark of Mesenchymal Chondrosarcoma is a biphasic pattern consisting of poorly differentiated small round cells interspersed with abrupt islands of well-differentiated [...].
Mesenchymal chondrosarcoma. This gross pathology picture of a bone surface tumour demonstrates a well-delineated and circumscribed tumour with zonal white cartilaginous (closer to bone surface) and tan-pink solid components.
Mesenchymal chondrosarcoma. Round cells with central zonal cartilage and bone.
A: hyaline cartilage
Back Extra: Mesenchymal Chondrosarcoma
- Clinical: Mesenchymal chondrosarcoma presents with pain and swelling, and 15% of patients have metastasis at presentation.
- Micro: Characterized by a biphasic appearance with small to medium-sized, poorly differentiated round cells and islands of well-differentiated hyaline cartilage.
- Ancillary: Mesenchymal chondrosarcoma harbours a recurrent HEY1-NCOA2 rearrangement, a defining molecular diagnostic marker.
Reference Gallery:
Mesenchymal chondrosarcoma. This gross pathology picture of a bone surface tumour demonstrates a well-delineated and circumscribed tumour with zonal white cartilaginous (closer to bone surface) and tan-pink solid components.
Mesenchymal chondrosarcoma. Mesenchymal chondrosarcoma may uncommonly show spindle cell morphology and eosinophilic matrix resembling osteoid.
Mesenchymal chondrosarcoma. Staghorn or pericytoid vascular pattern present in the undifferentiated area.
Mesenchymal chondrosarcoma. A round cell tumour of undifferentiated tumour cells, which may be seen in small biopsies.
Mesenchymal chondrosarcoma. Round cells with central zonal cartilage and bone.
Mesenchymal chondrosarcoma. Linear progression from resting chondrocytes to proliferating to hypertrophic to endochondral ossification to bone.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. CT showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. T1-weighted MRI showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. T1-weighted MRI with gadolinium enhancement showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. T2-weighted MRI showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.

Q: The undifferentiated small round cell areas of Mesenchymal Chondrosarcoma frequently demonstrate a prominent pericytoid or [...] vascular pattern.
Mesenchymal chondrosarcoma. Staghorn or pericytoid vascular pattern present in the undifferentiated area.
A: staghorn
Back Extra: Mesenchymal Chondrosarcoma
- Clinical: Mesenchymal chondrosarcoma presents with pain and swelling, and 15% of patients have metastasis at presentation.
- Micro: Characterized by a biphasic appearance with small to medium-sized, poorly differentiated round cells and islands of well-differentiated hyaline cartilage.
- Ancillary: Mesenchymal chondrosarcoma harbours a recurrent HEY1-NCOA2 rearrangement, a defining molecular diagnostic marker.
Reference Gallery:
Mesenchymal chondrosarcoma. This gross pathology picture of a bone surface tumour demonstrates a well-delineated and circumscribed tumour with zonal white cartilaginous (closer to bone surface) and tan-pink solid components.
Mesenchymal chondrosarcoma. Mesenchymal chondrosarcoma may uncommonly show spindle cell morphology and eosinophilic matrix resembling osteoid.
Mesenchymal chondrosarcoma. Staghorn or pericytoid vascular pattern present in the undifferentiated area.
Mesenchymal chondrosarcoma. A round cell tumour of undifferentiated tumour cells, which may be seen in small biopsies.
Mesenchymal chondrosarcoma. Round cells with central zonal cartilage and bone.
Mesenchymal chondrosarcoma. Linear progression from resting chondrocytes to proliferating to hypertrophic to endochondral ossification to bone.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. CT showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. T1-weighted MRI showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. T1-weighted MRI with gadolinium enhancement showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. T2-weighted MRI showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.

Q: A recurrent [NCOA2] gene rearrangement serves as the defining molecular diagnostic marker for Mesenchymal Chondrosarcoma.
Mesenchymal chondrosarcoma. A round cell tumour of undifferentiated tumour cells, which may be seen in small biopsies.
A: HEY1
Back Extra: Mesenchymal Chondrosarcoma
- Clinical: Mesenchymal chondrosarcoma presents with pain and swelling, and 15% of patients have metastasis at presentation.
- Micro: Characterized by a biphasic appearance with small to medium-sized, poorly differentiated round cells and islands of well-differentiated hyaline cartilage.
- Ancillary: Mesenchymal chondrosarcoma harbours a recurrent HEY1-NCOA2 rearrangement, a defining molecular diagnostic marker.
Reference Gallery:
Mesenchymal chondrosarcoma. This gross pathology picture of a bone surface tumour demonstrates a well-delineated and circumscribed tumour with zonal white cartilaginous (closer to bone surface) and tan-pink solid components.
Mesenchymal chondrosarcoma. Mesenchymal chondrosarcoma may uncommonly show spindle cell morphology and eosinophilic matrix resembling osteoid.
Mesenchymal chondrosarcoma. Staghorn or pericytoid vascular pattern present in the undifferentiated area.
Mesenchymal chondrosarcoma. A round cell tumour of undifferentiated tumour cells, which may be seen in small biopsies.
Mesenchymal chondrosarcoma. Round cells with central zonal cartilage and bone.
Mesenchymal chondrosarcoma. Linear progression from resting chondrocytes to proliferating to hypertrophic to endochondral ossification to bone.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. CT showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. T1-weighted MRI showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. T1-weighted MRI with gadolinium enhancement showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.
Mesenchymal chondrosarcoma involving the left pedicle of the eighth thoracic vertebra. T2-weighted MRI showing an osteolytic and destructive lesion with irregular calcification accompanied by extraosseous extension into the soft tissue in the vertebral foramen and spinal canal.

Q: Grossly and radiologically, Periosteal Chondrosarcoma presents as a lobulated cartilaginous surface tumor that predominantly arises in the [...] of long tubular bones (most commonly the distal femur and humerus).
Periosteal chondrosarcoma. Conventional radiograph of the left humerus, with a periosteal tumour extending into the soft tissue.
Periosteal chondrosarcoma. Gross features of the same periosteal chondrosarcoma shown in Fig. #5777 show a large lobulated cartilaginous tumour (diameter: 5.5 cm) at the surface of bone, with growth into the cortex.
A: metaphysis
Back Extra: Periosteal Chondrosarcoma
- Clinical: Periosteal chondrosarcoma predominantly affects the metaphysis of long tubular bones, most commonly the distal femur and humerus. Patients often present with pain and swelling.
- Micro: The tumour is characterized by a lobular, moderately cellular cartilaginous neoplasm with a myxoid matrix, calcification, and metaplastic bone formation.
- Ancillary: IDH1 and IDH2 mutations are occasionally found, but the diagnosis is primarily based on histopathology and imaging findings.
Reference Gallery:
Periosteal chondrosarcoma. Conventional radiograph of the left humerus, with a periosteal tumour extending into the soft tissue.
Periosteal chondrosarcoma. Gross features of the same periosteal chondrosarcoma shown in Fig. #5777 show a large lobulated cartilaginous tumour (diameter: 5.5 cm) at the surface of bone, with growth into the cortex.
Periosteal chondrosarcoma. Axial T1-weighted MRI (with fat suppression after intravenous contrast administration) showing a periosteal tumour (diameter: 5.5 cm) with septonodular enhancement typical for a cartilaginous tumour.
Periosteal chondrosarcoma. Cortical extension (arrowhead) of the cartilaginous tumour.
Periosteal chondrosarcoma. Formation of metaplastic bone (arrowhead) on the edges of the cartilaginous lobules.
Periosteal chondrosarcoma. Occasionally, cartilage tumour lobules may be observed in the medullary bone (arrowheads).

Q: A key microscopic diagnostic feature of Periosteal Chondrosarcoma is a moderately cellular, lobular cartilaginous tumor that characteristically forms [...] along the edges of the cartilage lobules.
Periosteal chondrosarcoma. Formation of metaplastic bone (arrowhead) on the edges of the cartilaginous lobules.
A: metaplastic bone
Back Extra: Periosteal Chondrosarcoma
- Clinical: Periosteal chondrosarcoma predominantly affects the metaphysis of long tubular bones, most commonly the distal femur and humerus. Patients often present with pain and swelling.
- Micro: The tumour is characterized by a lobular, moderately cellular cartilaginous neoplasm with a myxoid matrix, calcification, and metaplastic bone formation.
- Ancillary: IDH1 and IDH2 mutations are occasionally found, but the diagnosis is primarily based on histopathology and imaging findings.
Reference Gallery:
Periosteal chondrosarcoma. Conventional radiograph of the left humerus, with a periosteal tumour extending into the soft tissue.
Periosteal chondrosarcoma. Gross features of the same periosteal chondrosarcoma shown in Fig. #5777 show a large lobulated cartilaginous tumour (diameter: 5.5 cm) at the surface of bone, with growth into the cortex.
Periosteal chondrosarcoma. Axial T1-weighted MRI (with fat suppression after intravenous contrast administration) showing a periosteal tumour (diameter: 5.5 cm) with septonodular enhancement typical for a cartilaginous tumour.
Periosteal chondrosarcoma. Cortical extension (arrowhead) of the cartilaginous tumour.
Periosteal chondrosarcoma. Formation of metaplastic bone (arrowhead) on the edges of the cartilaginous lobules.
Periosteal chondrosarcoma. Occasionally, cartilage tumour lobules may be observed in the medullary bone (arrowheads).

Q: Desmoplastic Fibroma of Bone is a low-cellularity tumor characterized microscopically by fascicles of bland [...] embedded in a dense collagenous matrix.
Desmoplastic fibroma of bone. Tumour with fascicles of fibroblastic spindle cells embedded in fibrillary collagen.
A: spindle cells
Back Extra: Desmoplastic Fibroma of Bone
- Clinical: Desmoplastic fibroma of bone often presents with a longstanding history of pain or bone deformity, and in about 10% of cases, a pathological fracture is the presenting symptom.
- Micro: The tumour is characterized by a low cellularity with fascicles of bland spindle cells set in a collagenous matrix, and mitoses are scant.
- Ancillary: Molecular tests for GNAS single-nucleotide variants and MDM2 amplification should be performed to exclude fibrous dysplasia and low-grade central osteosarcoma, respectively.
Reference Gallery:
Desmoplastic fibroma of bone with a CTNNB1 (p.Ser45Phe) mutation. Plain radiograph showing a well-demarcated lytic tumour of the distal radius with cortical breakthrough, extension in surrounding soft tissue, and bowing of the ulna.
Desmoplastic fibroma of bone. Tumour with fascicles of fibroblastic spindle cells embedded in fibrillary collagen.
Desmoplastic fibroma of bone. Recurrent tumour showing invasion of bone and surrounding soft tissue. The cut surface of the tumour has a fibrous appearance.

Q: Desmoplastic Fibroma of Bone typically presents radiographically as a well-demarcated [...] lesion that may exhibit cortical breakthrough and soft tissue extension.
Desmoplastic fibroma of bone with a CTNNB1 (p.Ser45Phe) mutation. Plain radiograph showing a well-demarcated lytic tumour of the distal radius with cortical breakthrough, extension in surrounding soft tissue, and bowing of the ulna.
A: lytic
Back Extra: Desmoplastic Fibroma of Bone
- Clinical: Desmoplastic fibroma of bone often presents with a longstanding history of pain or bone deformity, and in about 10% of cases, a pathological fracture is the presenting symptom.
- Micro: The tumour is characterized by a low cellularity with fascicles of bland spindle cells set in a collagenous matrix, and mitoses are scant.
- Ancillary: Molecular tests for GNAS single-nucleotide variants and MDM2 amplification should be performed to exclude fibrous dysplasia and low-grade central osteosarcoma, respectively.
Reference Gallery:
Desmoplastic fibroma of bone with a CTNNB1 (p.Ser45Phe) mutation. Plain radiograph showing a well-demarcated lytic tumour of the distal radius with cortical breakthrough, extension in surrounding soft tissue, and bowing of the ulna.
Desmoplastic fibroma of bone. Tumour with fascicles of fibroblastic spindle cells embedded in fibrillary collagen.
Desmoplastic fibroma of bone. Recurrent tumour showing invasion of bone and surrounding soft tissue. The cut surface of the tumour has a fibrous appearance.

Q: Desmoplastic Fibroma of Bone can demonstrate local bone invasion macroscopically, featuring a distinctively [...] appearance on its cut surface.
Desmoplastic fibroma of bone. Recurrent tumour showing invasion of bone and surrounding soft tissue. The cut surface of the tumour has a fibrous appearance.
A: fibrous
Back Extra: Desmoplastic Fibroma of Bone
- Clinical: Desmoplastic fibroma of bone often presents with a longstanding history of pain or bone deformity, and in about 10% of cases, a pathological fracture is the presenting symptom.
- Micro: The tumour is characterized by a low cellularity with fascicles of bland spindle cells set in a collagenous matrix, and mitoses are scant.
- Ancillary: Molecular tests for GNAS single-nucleotide variants and MDM2 amplification should be performed to exclude fibrous dysplasia and low-grade central osteosarcoma, respectively.
Reference Gallery:
Desmoplastic fibroma of bone with a CTNNB1 (p.Ser45Phe) mutation. Plain radiograph showing a well-demarcated lytic tumour of the distal radius with cortical breakthrough, extension in surrounding soft tissue, and bowing of the ulna.
Desmoplastic fibroma of bone. Tumour with fascicles of fibroblastic spindle cells embedded in fibrillary collagen.
Desmoplastic fibroma of bone. Recurrent tumour showing invasion of bone and surrounding soft tissue. The cut surface of the tumour has a fibrous appearance.

Q: Histologically, Non-ossifying Fibroma is characterized by spindle-shaped cells arranged in a [...] pattern, accompanied by scattered osteoclast-type giant cells and foamy histiocytes.
Non-ossifying fibroma. Non-ossifying fibroma composed of spindle-shaped cells arranged in a storiform growth pattern, with scattered osteoclast-type giant cells.
Non-ossifying fibroma. Non-ossifying fibroma with large collections of foamy histiocytes.
A: storiform
Back Extra: Non-ossifying Fibroma
- Clinical: Non-ossifying fibromas are usually asymptomatic and found incidentally in skeletally immature individuals, typically in the second decade of life. Larger lesions can cause pain or pathological fractures.
- Micro: Histopathology shows spindle-shaped cells arranged in a storiform pattern, with scattered osteoclast-type giant cells and foamy histiocytes.
- Ancillary: KRAS and FGFR1 mutation testing can be considered in ambiguous cases to aid in diagnosis.
Reference Gallery:
Non-ossifying fibroma. Plain radiographs of non-ossifying fibromas of the distal radius (left) and the distal tibia (right). Both lesions are lobulated and well demarcated, with a sclerotic rim.
Non-ossifying fibroma. Coronal (left) and sagittal (right) formatted CT of a non-ossifying fibroma of the distal tibia.
Non-ossifying fibroma. Non-ossifying fibroma composed of spindle-shaped cells arranged in a storiform growth pattern, with scattered osteoclast-type giant cells.
Non-ossifying fibroma. Non-ossifying fibroma with large collections of foamy histiocytes.
Non-ossifying fibroma. Schema of signalling pathways involved in the pathogenesis of non-ossifying fibromas.

Q: On imaging, Non-ossifying Fibroma typically appears in skeletally immature individuals as a lobulated, well-demarcated radiolucent lesion bounded by a [...].
Non-ossifying fibroma. Plain radiographs of non-ossifying fibromas of the distal radius (left) and the distal tibia (right). Both lesions are lobulated and well demarcated, with a sclerotic rim.
Non-ossifying fibroma. Coronal (left) and sagittal (right) formatted CT of a non-ossifying fibroma of the distal tibia.
A: sclerotic rim
Back Extra: Non-ossifying Fibroma
- Clinical: Non-ossifying fibromas are usually asymptomatic and found incidentally in skeletally immature individuals, typically in the second decade of life. Larger lesions can cause pain or pathological fractures.
- Micro: Histopathology shows spindle-shaped cells arranged in a storiform pattern, with scattered osteoclast-type giant cells and foamy histiocytes.
- Ancillary: KRAS and FGFR1 mutation testing can be considered in ambiguous cases to aid in diagnosis.
Reference Gallery:
Non-ossifying fibroma. Plain radiographs of non-ossifying fibromas of the distal radius (left) and the distal tibia (right). Both lesions are lobulated and well demarcated, with a sclerotic rim.
Non-ossifying fibroma. Coronal (left) and sagittal (right) formatted CT of a non-ossifying fibroma of the distal tibia.
Non-ossifying fibroma. Non-ossifying fibroma composed of spindle-shaped cells arranged in a storiform growth pattern, with scattered osteoclast-type giant cells.
Non-ossifying fibroma. Non-ossifying fibroma with large collections of foamy histiocytes.
Non-ossifying fibroma. Schema of signalling pathways involved in the pathogenesis of non-ossifying fibromas.

Q: The pathogenesis of Non-ossifying Fibroma involves signaling pathway alterations, and diagnostic testing in ambiguous cases can evaluate for KRAS and [...] mutations.
Non-ossifying fibroma. Schema of signalling pathways involved in the pathogenesis of non-ossifying fibromas.
A: FGFR1
Back Extra: Non-ossifying Fibroma
- Clinical: Non-ossifying fibromas are usually asymptomatic and found incidentally in skeletally immature individuals, typically in the second decade of life. Larger lesions can cause pain or pathological fractures.
- Micro: Histopathology shows spindle-shaped cells arranged in a storiform pattern, with scattered osteoclast-type giant cells and foamy histiocytes.
- Ancillary: KRAS and FGFR1 mutation testing can be considered in ambiguous cases to aid in diagnosis.
Reference Gallery:
Non-ossifying fibroma. Plain radiographs of non-ossifying fibromas of the distal radius (left) and the distal tibia (right). Both lesions are lobulated and well demarcated, with a sclerotic rim.
Non-ossifying fibroma. Coronal (left) and sagittal (right) formatted CT of a non-ossifying fibroma of the distal tibia.
Non-ossifying fibroma. Non-ossifying fibroma composed of spindle-shaped cells arranged in a storiform growth pattern, with scattered osteoclast-type giant cells.
Non-ossifying fibroma. Non-ossifying fibroma with large collections of foamy histiocytes.
Non-ossifying fibroma. Schema of signalling pathways involved in the pathogenesis of non-ossifying fibromas.

Q: Microscopically, Fibrosarcoma of Bone is composed of a uniformly cellular population of undifferentiated spindle cells arranged in a [...] pattern, without a specific line of differentiation.
Fibrosarcoma. Fibrosarcoma is composed of undifferentiated spindle cells organized in fascicles. No specific line of differentiation is present.
A: fascicular
Q: Fibrosarcoma of Bone
- Clinical: The most common clinical signs and symptoms of [...] are local pain, swelling, limitation of motion, and pathological fracture.
- Micro: Microscopically, [...] is composed of a uniformly cellular population of spindle-shaped cells arranged in a fascicular pattern with a variable amount of collagen production.
- Ancillary: Molecular genetics plays a major role in excluding tumour-specific aberrations in [...]. Common losses include 6q, 8p, 9p, 10, 13, and 20p.
Reference Gallery:
Fibrosarcoma. Gross specimen of primary fibrosarcoma of bone. Cut surface is whitish and translucent, with more dense areas at the periphery.
Fibrosarcoma. Fibrosarcoma is composed of undifferentiated spindle cells organized in fascicles. No specific line of differentiation is present.
A: fibrosarcoma of bone; fibrosarcoma of bone; fibrosarcoma of bone

Q: Gross examination of primary [...] reveals a cut surface that is characteristically whitish and translucent, with denser areas at the periphery.
Fibrosarcoma. Gross specimen of primary fibrosarcoma of bone. Cut surface is whitish and translucent, with more dense areas at the periphery.
A: Fibrosarcoma of Bone
Q: Fibrosarcoma of Bone
- Clinical: The most common clinical signs and symptoms of [...] are local pain, swelling, limitation of motion, and pathological fracture.
- Micro: Microscopically, [...] is composed of a uniformly cellular population of spindle-shaped cells arranged in a fascicular pattern with a variable amount of collagen production.
- Ancillary: Molecular genetics plays a major role in excluding tumour-specific aberrations in [...]. Common losses include 6q, 8p, 9p, 10, 13, and 20p.
Reference Gallery:
Fibrosarcoma. Gross specimen of primary fibrosarcoma of bone. Cut surface is whitish and translucent, with more dense areas at the periphery.
Fibrosarcoma. Fibrosarcoma is composed of undifferentiated spindle cells organized in fascicles. No specific line of differentiation is present.
A: fibrosarcoma of bone; fibrosarcoma of bone; fibrosarcoma of bone

Q: Microscopically, [...] is characterized by blood-filled cystic spaces lacking a true endothelial lining, separated by fibrous septa containing reactive woven bone, hemorrhage, and osteoclast-like giant cells.
Aneurysmal bone cyst. Gross image of a resected specimen from the pelvic bone showing multiple haemorrhagic cystic spaces with intervening septations.
Aneurysmal bone cyst. Cyst wall showing lack of distinctive cell lining and composed of spindle cells with scattered osteoclast-like giant cells, haemorrhage, and haemosiderin pigment deposition.
A: Aneurysmal Bone Cyst
Back Extra: Aneurysmal Bone Cyst
- Clinical: Aneurysmal bone cyst (ABC) typically presents with pain and swelling, often in the long bones or vertebrae.
- Micro: The microscopic appearance of ABC is characterized by blood-filled cystic spaces separated by fibrous septa containing osteoclast-like giant cells and reactive woven bone.
- Ancillary: USP6 gene rearrangement is a key molecular finding in ABC, detectable by FISH.
Reference Gallery:
Aneurysmal bone cyst. Axial fat-suppressed T2-weighted MRI of the distal tibia demonstrates multiple fluid-fluid levels.
Aneurysmal bone cyst. Gross image of a resected specimen from the pelvic bone showing multiple haemorrhagic cystic spaces with intervening septations.
Aneurysmal bone cyst. Cyst wall with multiple septations.
Aneurysmal bone cyst. Cyst wall showing lack of distinctive cell lining and composed of spindle cells with scattered osteoclast-like giant cells, haemorrhage, and haemosiderin pigment deposition.
Aneurysmal bone cyst. Aneurysmal bone cyst with areas of basophilic blue bone formation.
Solid aneurysmal bone cyst. FISH for USP6 gene using break-apart probe showing split green and red signals indicating rearrangement.
Solid aneurysmal bone cyst. Tumour composed of fibroblast-like spindle cells, osteoclast-like giant cells, and reactive new bone formation.
Aneurysmal bone cyst. Lateral radiograph demonstrates an expansile multiloculated lytic lesion in the distal tibia.

Q: Primary Aneurysmal Bone Cyst is molecularly characterized by a gene rearrangement involving [...], which can be detected via fluorescence in situ hybridization (FISH).
Solid aneurysmal bone cyst. FISH for USP6 gene using break-apart probe showing split green and red signals indicating rearrangement.
A: USP6
Back Extra: Aneurysmal Bone Cyst
- Clinical: Aneurysmal bone cyst (ABC) typically presents with pain and swelling, often in the long bones or vertebrae.
- Micro: The microscopic appearance of ABC is characterized by blood-filled cystic spaces separated by fibrous septa containing osteoclast-like giant cells and reactive woven bone.
- Ancillary: USP6 gene rearrangement is a key molecular finding in ABC, detectable by FISH.
Reference Gallery:
Aneurysmal bone cyst. Axial fat-suppressed T2-weighted MRI of the distal tibia demonstrates multiple fluid-fluid levels.
Aneurysmal bone cyst. Gross image of a resected specimen from the pelvic bone showing multiple haemorrhagic cystic spaces with intervening septations.
Aneurysmal bone cyst. Cyst wall with multiple septations.
Aneurysmal bone cyst. Cyst wall showing lack of distinctive cell lining and composed of spindle cells with scattered osteoclast-like giant cells, haemorrhage, and haemosiderin pigment deposition.
Aneurysmal bone cyst. Aneurysmal bone cyst with areas of basophilic blue bone formation.
Solid aneurysmal bone cyst. FISH for USP6 gene using break-apart probe showing split green and red signals indicating rearrangement.
Solid aneurysmal bone cyst. Tumour composed of fibroblast-like spindle cells, osteoclast-like giant cells, and reactive new bone formation.
Aneurysmal bone cyst. Lateral radiograph demonstrates an expansile multiloculated lytic lesion in the distal tibia.

Q: On magnetic resonance imaging (MRI), an Aneurysmal Bone Cyst classically demonstrates multiple [...] within an expansile, multiloculated lytic bone lesion.
Aneurysmal bone cyst. Axial fat-suppressed T2-weighted MRI of the distal tibia demonstrates multiple fluid-fluid levels.
Aneurysmal bone cyst. Lateral radiograph demonstrates an expansile multiloculated lytic lesion in the distal tibia.
A: fluid-fluid levels
Back Extra: Aneurysmal Bone Cyst
- Clinical: Aneurysmal bone cyst (ABC) typically presents with pain and swelling, often in the long bones or vertebrae.
- Micro: The microscopic appearance of ABC is characterized by blood-filled cystic spaces separated by fibrous septa containing osteoclast-like giant cells and reactive woven bone.
- Ancillary: USP6 gene rearrangement is a key molecular finding in ABC, detectable by FISH.
Reference Gallery:
Aneurysmal bone cyst. Axial fat-suppressed T2-weighted MRI of the distal tibia demonstrates multiple fluid-fluid levels.
Aneurysmal bone cyst. Gross image of a resected specimen from the pelvic bone showing multiple haemorrhagic cystic spaces with intervening septations.
Aneurysmal bone cyst. Cyst wall with multiple septations.
Aneurysmal bone cyst. Cyst wall showing lack of distinctive cell lining and composed of spindle cells with scattered osteoclast-like giant cells, haemorrhage, and haemosiderin pigment deposition.
Aneurysmal bone cyst. Aneurysmal bone cyst with areas of basophilic blue bone formation.
Solid aneurysmal bone cyst. FISH for USP6 gene using break-apart probe showing split green and red signals indicating rearrangement.
Solid aneurysmal bone cyst. Tumour composed of fibroblast-like spindle cells, osteoclast-like giant cells, and reactive new bone formation.
Aneurysmal bone cyst. Lateral radiograph demonstrates an expansile multiloculated lytic lesion in the distal tibia.

Q: In Erdheim-Chester Disease, perirenal infiltration by histiocytes can produce a highly characteristic radiologic appearance on CT known as the [...] sign.
Erdheim–Chester disease. The hairy kidney sign. CT showing perirenal infiltration by Erdheim–Chester disease.
A: hairy kidney
Back Extra: Erdheim-Chester Disease
- Clinical: Erdheim-Chester Disease is characterized by bone pain, exophthalmos, xanthelasma, and diabetes insipidus, with 95% of patients showing symmetrical osteosclerosis of the leg bones.
- Micro: Histopathology shows infiltration of foamy histiocytes, Touton giant cells, and fibrosis. Histiocytes are positive for CD163, CD68, and CD14 but negative for CD1a and CD207.
- Ancillary: A BRAF p.Val600Glu mutation is present in 50-60% of ECD cases, and other mutations in the MAPK pathway (ARAF, NRAS, KRAS, MAP2K1) may also be found.
Reference Gallery:
Erdheim–Chester disease. The hairy kidney sign. CT showing perirenal infiltration by Erdheim–Chester disease.
Erdheim–Chester disease. Coronal T1-weighted spin echo MRI showing heterogeneous marrow abnormality throughout both femoral shafts in a 46-year-old man.
Erdheim–Chester disease. Short-tau inversion recovery (STIR) MRI showing heterogeneous marrow abnormality throughout both femoral shafts in a 46-year-old man.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy showing infiltration by foamy histiocytes.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy showing predominant fibrosis.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy. Immunohistochemistry shows expression of CD163.
Erdheim–Chester disease. Brain xanthogranuloma in a patient with typical bone lesions.
Erdheim–Chester disease. Brain xanthogranuloma in a patient with typical bone lesions, showing diffuse immunoreactivity for CD14.
Erdheim–Chester disease. Brain xanthogranuloma in a patient with typical bone lesions, showing immunoreactivity for factor XIIIa.
Erdheim–Chester disease. Characteristic bone infiltration by the histiocytic proliferation.

Q: Nearly all patients with Erdheim-Chester Disease demonstrate symmetric [...] of the long bones (e.g., femur and tibia), which correlates with histiocytic marrow infiltration and presents clinically as bone pain.
Erdheim–Chester disease. Coronal T1-weighted spin echo MRI showing heterogeneous marrow abnormality throughout both femoral shafts in a 46-year-old man.
Erdheim–Chester disease. Short-tau inversion recovery (STIR) MRI showing heterogeneous marrow abnormality throughout both femoral shafts in a 46-year-old man.
Erdheim–Chester disease. Characteristic bone infiltration by the histiocytic proliferation.
A: osteosclerosis
Back Extra: Erdheim-Chester Disease
- Clinical: Erdheim-Chester Disease is characterized by bone pain, exophthalmos, xanthelasma, and diabetes insipidus, with 95% of patients showing symmetrical osteosclerosis of the leg bones.
- Micro: Histopathology shows infiltration of foamy histiocytes, Touton giant cells, and fibrosis. Histiocytes are positive for CD163, CD68, and CD14 but negative for CD1a and CD207.
- Ancillary: A BRAF p.Val600Glu mutation is present in 50-60% of ECD cases, and other mutations in the MAPK pathway (ARAF, NRAS, KRAS, MAP2K1) may also be found.
Reference Gallery:
Erdheim–Chester disease. The hairy kidney sign. CT showing perirenal infiltration by Erdheim–Chester disease.
Erdheim–Chester disease. Coronal T1-weighted spin echo MRI showing heterogeneous marrow abnormality throughout both femoral shafts in a 46-year-old man.
Erdheim–Chester disease. Short-tau inversion recovery (STIR) MRI showing heterogeneous marrow abnormality throughout both femoral shafts in a 46-year-old man.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy showing infiltration by foamy histiocytes.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy showing predominant fibrosis.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy. Immunohistochemistry shows expression of CD163.
Erdheim–Chester disease. Brain xanthogranuloma in a patient with typical bone lesions.
Erdheim–Chester disease. Brain xanthogranuloma in a patient with typical bone lesions, showing diffuse immunoreactivity for CD14.
Erdheim–Chester disease. Brain xanthogranuloma in a patient with typical bone lesions, showing immunoreactivity for factor XIIIa.
Erdheim–Chester disease. Characteristic bone infiltration by the histiocytic proliferation.

Q: Biopsies of [...] typically reveal an infiltration of foamy histiocytes and Touton giant cells set within a background of marked fibrosis (histiocytes are typically positive for CD163 and negative for CD1a).
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy showing infiltration by foamy histiocytes.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy showing predominant fibrosis.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy. Immunohistochemistry shows expression of CD163.
A: Erdheim-Chester Disease
Back Extra: Erdheim-Chester Disease
- Clinical: Erdheim-Chester Disease is characterized by bone pain, exophthalmos, xanthelasma, and diabetes insipidus, with 95% of patients showing symmetrical osteosclerosis of the leg bones.
- Micro: Histopathology shows infiltration of foamy histiocytes, Touton giant cells, and fibrosis. Histiocytes are positive for CD163, CD68, and CD14 but negative for CD1a and CD207.
- Ancillary: A BRAF p.Val600Glu mutation is present in 50-60% of ECD cases, and other mutations in the MAPK pathway (ARAF, NRAS, KRAS, MAP2K1) may also be found.
Reference Gallery:
Erdheim–Chester disease. The hairy kidney sign. CT showing perirenal infiltration by Erdheim–Chester disease.
Erdheim–Chester disease. Coronal T1-weighted spin echo MRI showing heterogeneous marrow abnormality throughout both femoral shafts in a 46-year-old man.
Erdheim–Chester disease. Short-tau inversion recovery (STIR) MRI showing heterogeneous marrow abnormality throughout both femoral shafts in a 46-year-old man.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy showing infiltration by foamy histiocytes.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy showing predominant fibrosis.
Erdheim–Chester disease. Retroperitoneal (perirenal) biopsy. Immunohistochemistry shows expression of CD163.
Erdheim–Chester disease. Brain xanthogranuloma in a patient with typical bone lesions.
Erdheim–Chester disease. Brain xanthogranuloma in a patient with typical bone lesions, showing diffuse immunoreactivity for CD14.
Erdheim–Chester disease. Brain xanthogranuloma in a patient with typical bone lesions, showing immunoreactivity for factor XIIIa.
Erdheim–Chester disease. Characteristic bone infiltration by the histiocytic proliferation.

Q: Microscopically, Langerhans Cell Histiocytosis features diagnostic cells with characteristic folded or [...] nuclei, frequently admixed with numerous eosinophils and giant cells.
Langerhans cell histiocytosis. Low-power image of bone Langerhans cell histiocytosis with clusters of Langerhans cells and large numbers of eosinophils and osteoclast-like giant cells.
Langerhans cell histiocytosis. High-power image of Langerhans cell histiocytosis showing distinctive morphology of intermediate-sized cells with nuclear grooves, irregular nuclear contours, and pale eosinophilic cytoplasm.
A: grooved
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Langerhans Cell Histiocytosis can present as painful lytic bone lesions, often in the skull or long bones, with associated soft tissue masses. In multisystem disease, patients may have fever, cytopenias, and hepatosplenomegaly.
- Micro: Diagnostic cells in Langerhans Cell Histiocytosis have grooved, folded, or lobed nuclei with fine chromatin and minimal nuclear atypia. They are surrounded by eosinophils, histiocytes, and occasional giant cells.
- Ancillary: Langerhans Cell Histiocytosis cells express CD1a, CD207 (langerin), and S100. Over 85% of cases have BRAF or MAPK pathway mutations, most commonly BRAF p.Val600Glu.
Reference Gallery:
Langerhans cell histiocytosis. Low-power image of bone Langerhans cell histiocytosis with clusters of Langerhans cells and large numbers of eosinophils and osteoclast-like giant cells.
Langerhans cell histiocytosis. High-power image of Langerhans cell histiocytosis showing distinctive morphology of intermediate-sized cells with nuclear grooves, irregular nuclear contours, and pale eosinophilic cytoplasm.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with surface CD1a immunoreactivity on the majority of cells.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with cytoplasmic granular positivity for CD207 (langerin) in the majority of Langerhans cells.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with molecularly confirmed BRAF p.Val600Glu mutation showing strong diffuse cytoplasmic granular VE1 positivity in Langerhans cells.
Langerhans cell histiocytosis. CT with a C2 vertebral lytic lesion of Langerhans cell histiocytosis.
Langerhans cell histiocytosis. CT of the skull without contrast. Lytic lesion in the right frontal bone with associated soft tissue component. Margins should be left intact for proper healing in cases of bone Langerhans cell histiocytosis.
Langerhans cell histiocytosis involving diaphysis of the left tibia. Plain X-ray shows a radiolucent lesion in the left tibia, with periosteal new bone formation.
Langerhans cell histiocytosis involving diaphysis of the left tibia. In the same case shown in Fig. #6500, MRI shows an intramedullary lesion in the tibial diaphysis with erosion of the adjacent cortex.

Q: Immunohistochemically, the neoplastic cells of Langerhans Cell Histiocytosis characteristically express S100, CD1a, and [...] (langerin).
Langerhans cell histiocytosis. Langerhans cell histiocytosis with surface CD1a immunoreactivity on the majority of cells.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with cytoplasmic granular positivity for CD207 (langerin) in the majority of Langerhans cells.
A: CD207
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Langerhans Cell Histiocytosis can present as painful lytic bone lesions, often in the skull or long bones, with associated soft tissue masses. In multisystem disease, patients may have fever, cytopenias, and hepatosplenomegaly.
- Micro: Diagnostic cells in Langerhans Cell Histiocytosis have grooved, folded, or lobed nuclei with fine chromatin and minimal nuclear atypia. They are surrounded by eosinophils, histiocytes, and occasional giant cells.
- Ancillary: Langerhans Cell Histiocytosis cells express CD1a, CD207 (langerin), and S100. Over 85% of cases have BRAF or MAPK pathway mutations, most commonly BRAF p.Val600Glu.
Reference Gallery:
Langerhans cell histiocytosis. Low-power image of bone Langerhans cell histiocytosis with clusters of Langerhans cells and large numbers of eosinophils and osteoclast-like giant cells.
Langerhans cell histiocytosis. High-power image of Langerhans cell histiocytosis showing distinctive morphology of intermediate-sized cells with nuclear grooves, irregular nuclear contours, and pale eosinophilic cytoplasm.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with surface CD1a immunoreactivity on the majority of cells.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with cytoplasmic granular positivity for CD207 (langerin) in the majority of Langerhans cells.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with molecularly confirmed BRAF p.Val600Glu mutation showing strong diffuse cytoplasmic granular VE1 positivity in Langerhans cells.
Langerhans cell histiocytosis. CT with a C2 vertebral lytic lesion of Langerhans cell histiocytosis.
Langerhans cell histiocytosis. CT of the skull without contrast. Lytic lesion in the right frontal bone with associated soft tissue component. Margins should be left intact for proper healing in cases of bone Langerhans cell histiocytosis.
Langerhans cell histiocytosis involving diaphysis of the left tibia. Plain X-ray shows a radiolucent lesion in the left tibia, with periosteal new bone formation.
Langerhans cell histiocytosis involving diaphysis of the left tibia. In the same case shown in Fig. #6500, MRI shows an intramedullary lesion in the tibial diaphysis with erosion of the adjacent cortex.

Q: A classic radiologic and clinical presentation of Langerhans Cell Histiocytosis is the presence of painful [...] bone lesions, which frequently involve the skull or long bones.
Langerhans cell histiocytosis. CT of the skull without contrast. Lytic lesion in the right frontal bone with associated soft tissue component. Margins should be left intact for proper healing in cases of bone Langerhans cell histiocytosis.
Langerhans cell histiocytosis involving diaphysis of the left tibia. Plain X-ray shows a radiolucent lesion in the left tibia, with periosteal new bone formation.
A: lytic
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Langerhans Cell Histiocytosis can present as painful lytic bone lesions, often in the skull or long bones, with associated soft tissue masses. In multisystem disease, patients may have fever, cytopenias, and hepatosplenomegaly.
- Micro: Diagnostic cells in Langerhans Cell Histiocytosis have grooved, folded, or lobed nuclei with fine chromatin and minimal nuclear atypia. They are surrounded by eosinophils, histiocytes, and occasional giant cells.
- Ancillary: Langerhans Cell Histiocytosis cells express CD1a, CD207 (langerin), and S100. Over 85% of cases have BRAF or MAPK pathway mutations, most commonly BRAF p.Val600Glu.
Reference Gallery:
Langerhans cell histiocytosis. Low-power image of bone Langerhans cell histiocytosis with clusters of Langerhans cells and large numbers of eosinophils and osteoclast-like giant cells.
Langerhans cell histiocytosis. High-power image of Langerhans cell histiocytosis showing distinctive morphology of intermediate-sized cells with nuclear grooves, irregular nuclear contours, and pale eosinophilic cytoplasm.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with surface CD1a immunoreactivity on the majority of cells.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with cytoplasmic granular positivity for CD207 (langerin) in the majority of Langerhans cells.
Langerhans cell histiocytosis. Langerhans cell histiocytosis with molecularly confirmed BRAF p.Val600Glu mutation showing strong diffuse cytoplasmic granular VE1 positivity in Langerhans cells.
Langerhans cell histiocytosis. CT with a C2 vertebral lytic lesion of Langerhans cell histiocytosis.
Langerhans cell histiocytosis. CT of the skull without contrast. Lytic lesion in the right frontal bone with associated soft tissue component. Margins should be left intact for proper healing in cases of bone Langerhans cell histiocytosis.
Langerhans cell histiocytosis involving diaphysis of the left tibia. Plain X-ray shows a radiolucent lesion in the left tibia, with periosteal new bone formation.
Langerhans cell histiocytosis involving diaphysis of the left tibia. In the same case shown in Fig. #6500, MRI shows an intramedullary lesion in the tibial diaphysis with erosion of the adjacent cortex.

Q: The characteristic histologic hallmark of Rosai-Dorfman Disease is the presence of large histiocytes exhibiting [...], defined as the presence of intact inflammatory cells within their cytoplasm.
Rosai–Dorfman disease. Numerous large histiocytes with abundant pale eosinophilic cytoplasm are surrounded by chronic inflammatory cells.
Rosai–Dorfman disease. Rosai–Dorfman histiocytes with emperipolesis.
A: emperipolesis
Back Extra: Rosai-Dorfman Disease
- Clinical: Patients with Rosai-Dorfman Disease typically present with localized pain and a well-defined lytic, sometimes expansile, septated mass on imaging.
- Micro: The tumour is characterized by sheets and clusters of large histiocytes with emperipolesis and a mixed inflammatory infiltrate.
- Ancillary: Histiocytes in Rosai-Dorfman Disease are S100-positive and negative for CD1a and CD207, with possible NRAS, KRAS, MAP2K1, ARAF, and BRAF mutations.
Reference Gallery:
Rosai–Dorfman disease. Radiograph showing distal femur that appears unremarkable.
Rosai–Dorfman disease. Tumour in medial femoral condyle that is bright on coronal fat-saturated T2-weighted image.
Rosai–Dorfman disease. Lesion replaces the normal marrow and surrounds the bony trabeculae.
Rosai–Dorfman disease. Numerous large histiocytes with abundant pale eosinophilic cytoplasm are surrounded by chronic inflammatory cells.
Rosai–Dorfman disease. Numerous neutrophils are present, which can lead to a misdiagnosis of osteomyelitis.
Rosai–Dorfman disease. Rosai–Dorfman histiocytes with emperipolesis.
Rosai–Dorfman disease. Rosai–Dorfman histiocytes are strongly immunoreactive for S100.

Q: Immunohistochemical staining in Rosai-Dorfman Disease typically demonstrates that the characteristic large histiocytes are negative for CD1a and CD207, but strongly positive for [...].
Rosai–Dorfman disease. Rosai–Dorfman histiocytes are strongly immunoreactive for S100.
A: S100
Back Extra: Rosai-Dorfman Disease
- Clinical: Patients with Rosai-Dorfman Disease typically present with localized pain and a well-defined lytic, sometimes expansile, septated mass on imaging.
- Micro: The tumour is characterized by sheets and clusters of large histiocytes with emperipolesis and a mixed inflammatory infiltrate.
- Ancillary: Histiocytes in Rosai-Dorfman Disease are S100-positive and negative for CD1a and CD207, with possible NRAS, KRAS, MAP2K1, ARAF, and BRAF mutations.
Reference Gallery:
Rosai–Dorfman disease. Radiograph showing distal femur that appears unremarkable.
Rosai–Dorfman disease. Tumour in medial femoral condyle that is bright on coronal fat-saturated T2-weighted image.
Rosai–Dorfman disease. Lesion replaces the normal marrow and surrounds the bony trabeculae.
Rosai–Dorfman disease. Numerous large histiocytes with abundant pale eosinophilic cytoplasm are surrounded by chronic inflammatory cells.
Rosai–Dorfman disease. Numerous neutrophils are present, which can lead to a misdiagnosis of osteomyelitis.
Rosai–Dorfman disease. Rosai–Dorfman histiocytes with emperipolesis.
Rosai–Dorfman disease. Rosai–Dorfman histiocytes are strongly immunoreactive for S100.

Q: On imaging, Primary Non-Hodgkin Lymphoma of Bone typically presents as a large, lytic, and destructive tumor with characteristic [...] or permeative borders.
Diffuse large B-cell lymphoma of bone. MRI of the right clavicle (single arrowhead) shows soft tissue extension (double arrowhead).
Diffuse large B-cell lymphoma of bone. A lesion in the right clavicle (arrowheads) on conventional X-ray.
A: moth-eaten
Back Extra: Primary Non-Hodgkin Lymphoma of Bone
- Clinical: Primary Non-Hodgkin Lymphoma of Bone typically presents with pain in the affected bone, and imaging shows a large, lytic, and destructive tumour with moth-eaten or permeative borders.
- Micro: The microscopic appearance of Primary Non-Hodgkin Lymphoma of Bone is characterized by a diffuse growth pattern of large, atypical lymphoid cells, often with prominent fibrosis and reactive changes in bony trabeculae.
- Ancillary: Immunohistochemical markers such as CD20, PAX5, and CD79a are crucial for diagnosing Primary Non-Hodgkin Lymphoma of Bone, and clonal rearrangements of immunoglobulin genes are detectable.
Reference Gallery:
Diffuse large B-cell lymphoma of bone. MRI of the right clavicle (single arrowhead) shows soft tissue extension (double arrowhead).
Diffuse large B-cell lymphoma of bone. A lesion in the right clavicle (arrowheads) on conventional X-ray.
Primary bone diffuse large B-cell lymphoma. Pleomorphic B cells with large irregular multilobulated nuclei and prominent nucleoli.
Primary bone diffuse large B-cell lymphoma. Crush and smear artefacts are frequently observed in primary bone diffuse large B-cell lymphoma.
Primary bone diffuse large B-cell lymphoma. Extensive immunoreactivity for CD20, a pan–B-cell marker, in tumour cells of this primary bone diffuse large B-cell lymphoma.
Primary bone diffuse large B-cell lymphoma. Extensive sclerosis with crush artefact in a case of primary bone diffuse large B-cell lymphoma mimicking sarcoma.
Primary bone diffuse large B-cell lymphoma. PAX5 immunoreactivity highlights the spindle cell appearance of the neoplastic B cells.

Q: Microscopically, Primary Non-Hodgkin Lymphoma of Bone features large, atypical lymphoid cells often accompanied by extensive sclerosis and prominent [...] artifacts, which can cause the lesion to mimic a sarcoma.
Primary bone diffuse large B-cell lymphoma. Crush and smear artefacts are frequently observed in primary bone diffuse large B-cell lymphoma.
Primary bone diffuse large B-cell lymphoma. Extensive sclerosis with crush artefact in a case of primary bone diffuse large B-cell lymphoma mimicking sarcoma.
A: crush and smear
Back Extra: Primary Non-Hodgkin Lymphoma of Bone
- Clinical: Primary Non-Hodgkin Lymphoma of Bone typically presents with pain in the affected bone, and imaging shows a large, lytic, and destructive tumour with moth-eaten or permeative borders.
- Micro: The microscopic appearance of Primary Non-Hodgkin Lymphoma of Bone is characterized by a diffuse growth pattern of large, atypical lymphoid cells, often with prominent fibrosis and reactive changes in bony trabeculae.
- Ancillary: Immunohistochemical markers such as CD20, PAX5, and CD79a are crucial for diagnosing Primary Non-Hodgkin Lymphoma of Bone, and clonal rearrangements of immunoglobulin genes are detectable.
Reference Gallery:
Diffuse large B-cell lymphoma of bone. MRI of the right clavicle (single arrowhead) shows soft tissue extension (double arrowhead).
Diffuse large B-cell lymphoma of bone. A lesion in the right clavicle (arrowheads) on conventional X-ray.
Primary bone diffuse large B-cell lymphoma. Pleomorphic B cells with large irregular multilobulated nuclei and prominent nucleoli.
Primary bone diffuse large B-cell lymphoma. Crush and smear artefacts are frequently observed in primary bone diffuse large B-cell lymphoma.
Primary bone diffuse large B-cell lymphoma. Extensive immunoreactivity for CD20, a pan–B-cell marker, in tumour cells of this primary bone diffuse large B-cell lymphoma.
Primary bone diffuse large B-cell lymphoma. Extensive sclerosis with crush artefact in a case of primary bone diffuse large B-cell lymphoma mimicking sarcoma.
Primary bone diffuse large B-cell lymphoma. PAX5 immunoreactivity highlights the spindle cell appearance of the neoplastic B cells.

Q: The diagnosis of Primary Non-Hodgkin Lymphoma of Bone is supported by immunohistochemical positivity for pan-B-cell markers such as CD20 and [...], the latter of which may unusually highlight a spindle cell appearance in the neoplastic cells.
Primary bone diffuse large B-cell lymphoma. Extensive immunoreactivity for CD20, a pan–B-cell marker, in tumour cells of this primary bone diffuse large B-cell lymphoma.
Primary bone diffuse large B-cell lymphoma. PAX5 immunoreactivity highlights the spindle cell appearance of the neoplastic B cells.
A: PAX5
Back Extra: Primary Non-Hodgkin Lymphoma of Bone
- Clinical: Primary Non-Hodgkin Lymphoma of Bone typically presents with pain in the affected bone, and imaging shows a large, lytic, and destructive tumour with moth-eaten or permeative borders.
- Micro: The microscopic appearance of Primary Non-Hodgkin Lymphoma of Bone is characterized by a diffuse growth pattern of large, atypical lymphoid cells, often with prominent fibrosis and reactive changes in bony trabeculae.
- Ancillary: Immunohistochemical markers such as CD20, PAX5, and CD79a are crucial for diagnosing Primary Non-Hodgkin Lymphoma of Bone, and clonal rearrangements of immunoglobulin genes are detectable.
Reference Gallery:
Diffuse large B-cell lymphoma of bone. MRI of the right clavicle (single arrowhead) shows soft tissue extension (double arrowhead).
Diffuse large B-cell lymphoma of bone. A lesion in the right clavicle (arrowheads) on conventional X-ray.
Primary bone diffuse large B-cell lymphoma. Pleomorphic B cells with large irregular multilobulated nuclei and prominent nucleoli.
Primary bone diffuse large B-cell lymphoma. Crush and smear artefacts are frequently observed in primary bone diffuse large B-cell lymphoma.
Primary bone diffuse large B-cell lymphoma. Extensive immunoreactivity for CD20, a pan–B-cell marker, in tumour cells of this primary bone diffuse large B-cell lymphoma.
Primary bone diffuse large B-cell lymphoma. Extensive sclerosis with crush artefact in a case of primary bone diffuse large B-cell lymphoma mimicking sarcoma.
Primary bone diffuse large B-cell lymphoma. PAX5 immunoreactivity highlights the spindle cell appearance of the neoplastic B cells.

Q: In Solitary Plasmacytoma of Bone, histopathology reveals sheets of neoplastic plasma cells that characteristically express the immunohistochemical marker [...].
Plasmacytoma of bone. In this case, neoplastic plasma cells are mostly small and mature.
Plasmacytoma of bone. Neoplastic plasma cells are CD138-positive on immunohistochemistry. They were also positive for CD56 and monotypic kappa (not shown).
A: CD138
Back Extra: Solitary Plasmacytoma of Bone
- Clinical: Patients typically present with localized pain, sometimes accompanied by fracture, and often have a serum or urine M component.
- Micro: Histopathology shows sheets of neoplastic plasma cells, which can be small and mature or enlarged and atypical, and may be CD138-positive on immunohistochemistry.
- Ancillary: Molecular pathology reveals rearrangement of Ig heavy and light chain genes, and diagnostic criteria include a single osseous lesion, clonal plasma cells, and no evidence of PCM on staging bone marrow biopsy.
Reference Gallery:
Plasmacytoma of bone. Low power shows sheets of cells without intervening stroma.
Plasmacytoma of bone. In this case, neoplastic plasma cells are mostly small and mature.
Plasmacytoma of bone. Neoplastic plasma cells are CD138-positive on immunohistochemistry. They were also positive for CD56 and monotypic kappa (not shown).
Solitary plasmacytoma of bone. Axial CT image of the pelvis shows a well-defined lytic lesion (asterisk) in the posterior aspect of the left ilium. The cortex is thinned and there is mild expansile remodelling.
Solitary plasmacytoma of bone. Proton density MRI with fat saturation image of the pelvis shows a well-defined lytic lesion (asterisk) in the posterior aspect of the left ilium, with homogeneous, hyperintense marrow infiltration.
Solitary plasmacytoma of bone. Anteroposterior radiograph of the right humerus shows geographical destruction consisting of patchy bone lysis. There is no surrounding sclerosis and the cortex is mildly thinned (arrows) but intact.

Q: Radiographic imaging of Solitary Plasmacytoma of Bone typically demonstrates a solitary, well-defined [...] bone lesion, often with cortical thinning but lacking surrounding sclerosis.
Solitary plasmacytoma of bone. Axial CT image of the pelvis shows a well-defined lytic lesion (asterisk) in the posterior aspect of the left ilium. The cortex is thinned and there is mild expansile remodelling.
Solitary plasmacytoma of bone. Anteroposterior radiograph of the right humerus shows geographical destruction consisting of patchy bone lysis. There is no surrounding sclerosis and the cortex is mildly thinned (arrows) but intact.
A: lytic
Back Extra: Solitary Plasmacytoma of Bone
- Clinical: Patients typically present with localized pain, sometimes accompanied by fracture, and often have a serum or urine M component.
- Micro: Histopathology shows sheets of neoplastic plasma cells, which can be small and mature or enlarged and atypical, and may be CD138-positive on immunohistochemistry.
- Ancillary: Molecular pathology reveals rearrangement of Ig heavy and light chain genes, and diagnostic criteria include a single osseous lesion, clonal plasma cells, and no evidence of PCM on staging bone marrow biopsy.
Reference Gallery:
Plasmacytoma of bone. Low power shows sheets of cells without intervening stroma.
Plasmacytoma of bone. In this case, neoplastic plasma cells are mostly small and mature.
Plasmacytoma of bone. Neoplastic plasma cells are CD138-positive on immunohistochemistry. They were also positive for CD56 and monotypic kappa (not shown).
Solitary plasmacytoma of bone. Axial CT image of the pelvis shows a well-defined lytic lesion (asterisk) in the posterior aspect of the left ilium. The cortex is thinned and there is mild expansile remodelling.
Solitary plasmacytoma of bone. Proton density MRI with fat saturation image of the pelvis shows a well-defined lytic lesion (asterisk) in the posterior aspect of the left ilium, with homogeneous, hyperintense marrow infiltration.
Solitary plasmacytoma of bone. Anteroposterior radiograph of the right humerus shows geographical destruction consisting of patchy bone lysis. There is no surrounding sclerosis and the cortex is mildly thinned (arrows) but intact.

Q: Microscopically, Benign Notochordal Cell Tumor is characterized by solid sheets of bland, [...] tumor cells that lack mitotic activity.
Benign notochordal cell tumour. Benign notochordal cell tumour consists of solid sheets of vacuolated tumour cells with bland nuclei. The tumour cells mimic mature fat or brown fat cells.
A: adipocyte-like vacuolated
Back Extra: Benign Notochordal Cell Tumour
- Clinical: Benign Notochordal Cell Tumours (BNCTs) are usually found incidentally on imaging and may be associated with pain. They are most commonly found in the vertebral bodies or the clivus.
- Micro: BNCT consists of solid sheets of adipocyte-like vacuolated tumour cells and eosinophilic, less-vacuolated tumour cells. The nuclei are usually bland and mitotic figures are absent.
- Ancillary: Both BNCT and EPS are immunoreactive for brachyury (encoded by TBXT), cytokeratin, EMA, and (variably) S100.
Reference Gallery:
Benign notochordal cell tumour. Benign notochordal cell tumour consists of solid sheets of vacuolated tumour cells with bland nuclei. The tumour cells mimic mature fat or brown fat cells.
Benign notochordal cell tumour. Benign notochordal cell tumour reveals scattered residual bone marrow islands within the lesion.
Benign notochordal cell tumour. The affected bone trabeculae show appositional bone formation and no osteolytic process.
Benign notochordal cell tumour coexisting with conventional chordoma. This tumour shows a focus of benign notochordal cell tumour (right) coexisting with conventional chordoma (left).
Benign notochordal cell tumour. Sagittal T1-weigthed MRI (left) and T2-weighted MRI (right) show a well-defined, intraosseous lesion in the first coccygeal vertebra, containing several small foci of hyperintense T1 signal, suggesting fat (arrow). Histological diagnosis was confirmed after coccygectomy for pain.
Benign notochordal cell tumour. Vertebral body with dense white lesion.

Q: Unlike conventional chordomas, Benign Notochordal Cell Tumor typically grows without an osteolytic process, often permeating trabeculae and entrapping scattered [...] islands within the lesion.
Benign notochordal cell tumour. Benign notochordal cell tumour reveals scattered residual bone marrow islands within the lesion.
Benign notochordal cell tumour. The affected bone trabeculae show appositional bone formation and no osteolytic process.
A: residual bone marrow
Back Extra: Benign Notochordal Cell Tumour
- Clinical: Benign Notochordal Cell Tumours (BNCTs) are usually found incidentally on imaging and may be associated with pain. They are most commonly found in the vertebral bodies or the clivus.
- Micro: BNCT consists of solid sheets of adipocyte-like vacuolated tumour cells and eosinophilic, less-vacuolated tumour cells. The nuclei are usually bland and mitotic figures are absent.
- Ancillary: Both BNCT and EPS are immunoreactive for brachyury (encoded by TBXT), cytokeratin, EMA, and (variably) S100.
Reference Gallery:
Benign notochordal cell tumour. Benign notochordal cell tumour consists of solid sheets of vacuolated tumour cells with bland nuclei. The tumour cells mimic mature fat or brown fat cells.
Benign notochordal cell tumour. Benign notochordal cell tumour reveals scattered residual bone marrow islands within the lesion.
Benign notochordal cell tumour. The affected bone trabeculae show appositional bone formation and no osteolytic process.
Benign notochordal cell tumour coexisting with conventional chordoma. This tumour shows a focus of benign notochordal cell tumour (right) coexisting with conventional chordoma (left).
Benign notochordal cell tumour. Sagittal T1-weigthed MRI (left) and T2-weighted MRI (right) show a well-defined, intraosseous lesion in the first coccygeal vertebra, containing several small foci of hyperintense T1 signal, suggesting fat (arrow). Histological diagnosis was confirmed after coccygectomy for pain.
Benign notochordal cell tumour. Vertebral body with dense white lesion.

Q: Radiographically and grossly, Benign Notochordal Cell Tumor typically presents as a well-defined, incidental intraosseous lesion most commonly located in the clivus or the [...].
Benign notochordal cell tumour. Sagittal T1-weigthed MRI (left) and T2-weighted MRI (right) show a well-defined, intraosseous lesion in the first coccygeal vertebra, containing several small foci of hyperintense T1 signal, suggesting fat (arrow). Histological diagnosis was confirmed after coccygectomy for pain.
Benign notochordal cell tumour. Vertebral body with dense white lesion.
A: vertebral bodies
Back Extra: Benign Notochordal Cell Tumour
- Clinical: Benign Notochordal Cell Tumours (BNCTs) are usually found incidentally on imaging and may be associated with pain. They are most commonly found in the vertebral bodies or the clivus.
- Micro: BNCT consists of solid sheets of adipocyte-like vacuolated tumour cells and eosinophilic, less-vacuolated tumour cells. The nuclei are usually bland and mitotic figures are absent.
- Ancillary: Both BNCT and EPS are immunoreactive for brachyury (encoded by TBXT), cytokeratin, EMA, and (variably) S100.
Reference Gallery:
Benign notochordal cell tumour. Benign notochordal cell tumour consists of solid sheets of vacuolated tumour cells with bland nuclei. The tumour cells mimic mature fat or brown fat cells.
Benign notochordal cell tumour. Benign notochordal cell tumour reveals scattered residual bone marrow islands within the lesion.
Benign notochordal cell tumour. The affected bone trabeculae show appositional bone formation and no osteolytic process.
Benign notochordal cell tumour coexisting with conventional chordoma. This tumour shows a focus of benign notochordal cell tumour (right) coexisting with conventional chordoma (left).
Benign notochordal cell tumour. Sagittal T1-weigthed MRI (left) and T2-weighted MRI (right) show a well-defined, intraosseous lesion in the first coccygeal vertebra, containing several small foci of hyperintense T1 signal, suggesting fat (arrow). Histological diagnosis was confirmed after coccygectomy for pain.
Benign notochordal cell tumour. Vertebral body with dense white lesion.

Q: Histologically, Conventional Chordoma is characterized by cords and nests of large, vacuolated, bubbly-appearing cells known as [...] cells embedded in an abundant myxoid matrix.
Chordoma. Tumour cells are arranged in cords and nests. Note the typical light basophilic appearance of the myxoid matrix.
Chordoma. Cords of tumour cells with mixed physaliphorous and epithelioid features.
A: physaliphorous
Back Extra: Conventional Chordoma
- Clinical: Conventional chordoma typically presents with pain and site-related neurological symptoms, and is often seen as a lytic, destructive lesion in the axial skeleton.
- Micro: The histopathology of conventional chordoma shows large epithelioid cells with clear to light eosinophilic cytoplasm, arranged in cords and nests within an abundant myxoid matrix.
- Ancillary: The tumour is diffusely immunoreactive for cytokeratin and EMA, and shows nuclear immunoreactivity for brachyury.
Reference Gallery:
Conventional chordoma. Sagittal T1 MRI shows a heterogeneous mass arising from the distal sacrum, extending within bone from S2 to the coccyx. There is a large anterior and small posterior extraosseous mass.
Chordoma. Classic appearance of conventional chordoma showing the lobulated architecture with abundant extracellular matrix.
Chordoma. Tumour cells are arranged in cords and nests. Note the typical light basophilic appearance of the myxoid matrix.
Chordoma. Cords of tumour cells with mixed physaliphorous and epithelioid features.
Chordoma. Cytological atypia including multinucleated cells with bizarre nuclei and pseudonuclear inclusion.
Chordoma. Tumour cells arranged in a pseudoalveolar pattern, mimicking renal cell carcinoma.
Chordoma. Nuclear immunoreactivity for brachyury.
Conventional chordoma. Sacrectomy specimen showing a large lobulated mass with a gelatinous appearance, invading and destroying the distal sacrum.
Conventional chordoma. Sagittal CT of the sacrum. There is destruction of the sacrum inferior to S1. Tumour extends proximally within the central spinal canal posterior to S1, the proximal level indicated (arrow). Bone fragments (arrowheads) remain visible anterior and posterior to tumour in the central spinal canal, which is expanded. Distally, there is an anterior extraosseous presacral mass (asterisk).

Q: Immunohistochemically, Conventional Chordoma is typically positive for cytokeratin and EMA, and characteristically shows diffuse nuclear immunoreactivity for [...], a highly specific transcription factor.
Chordoma. Nuclear immunoreactivity for brachyury.
A: brachyury
Back Extra: Conventional Chordoma
- Clinical: Conventional chordoma typically presents with pain and site-related neurological symptoms, and is often seen as a lytic, destructive lesion in the axial skeleton.
- Micro: The histopathology of conventional chordoma shows large epithelioid cells with clear to light eosinophilic cytoplasm, arranged in cords and nests within an abundant myxoid matrix.
- Ancillary: The tumour is diffusely immunoreactive for cytokeratin and EMA, and shows nuclear immunoreactivity for brachyury.
Reference Gallery:
Conventional chordoma. Sagittal T1 MRI shows a heterogeneous mass arising from the distal sacrum, extending within bone from S2 to the coccyx. There is a large anterior and small posterior extraosseous mass.
Chordoma. Classic appearance of conventional chordoma showing the lobulated architecture with abundant extracellular matrix.
Chordoma. Tumour cells are arranged in cords and nests. Note the typical light basophilic appearance of the myxoid matrix.
Chordoma. Cords of tumour cells with mixed physaliphorous and epithelioid features.
Chordoma. Cytological atypia including multinucleated cells with bizarre nuclei and pseudonuclear inclusion.
Chordoma. Tumour cells arranged in a pseudoalveolar pattern, mimicking renal cell carcinoma.
Chordoma. Nuclear immunoreactivity for brachyury.
Conventional chordoma. Sacrectomy specimen showing a large lobulated mass with a gelatinous appearance, invading and destroying the distal sacrum.
Conventional chordoma. Sagittal CT of the sacrum. There is destruction of the sacrum inferior to S1. Tumour extends proximally within the central spinal canal posterior to S1, the proximal level indicated (arrow). Bone fragments (arrowheads) remain visible anterior and posterior to tumour in the central spinal canal, which is expanded. Distally, there is an anterior extraosseous presacral mass (asterisk).

Q: The diagnosis of [...] should be strongly suspected when a lytic, destructive, gelatinous tumor is found arising almost exclusively in the axial skeleton (most frequently the sacrococcygeal region or spheno-occipital clivus).
Conventional chordoma. Sagittal T1 MRI shows a heterogeneous mass arising from the distal sacrum, extending within bone from S2 to the coccyx. There is a large anterior and small posterior extraosseous mass.
Conventional chordoma. Sacrectomy specimen showing a large lobulated mass with a gelatinous appearance, invading and destroying the distal sacrum.
Conventional chordoma. Sagittal CT of the sacrum. There is destruction of the sacrum inferior to S1. Tumour extends proximally within the central spinal canal posterior to S1, the proximal level indicated (arrow). Bone fragments (arrowheads) remain visible anterior and posterior to tumour in the central spinal canal, which is expanded. Distally, there is an anterior extraosseous presacral mass (asterisk).
A: Conventional Chordoma
Back Extra: Conventional Chordoma
- Clinical: Conventional chordoma typically presents with pain and site-related neurological symptoms, and is often seen as a lytic, destructive lesion in the axial skeleton.
- Micro: The histopathology of conventional chordoma shows large epithelioid cells with clear to light eosinophilic cytoplasm, arranged in cords and nests within an abundant myxoid matrix.
- Ancillary: The tumour is diffusely immunoreactive for cytokeratin and EMA, and shows nuclear immunoreactivity for brachyury.
Reference Gallery:
Conventional chordoma. Sagittal T1 MRI shows a heterogeneous mass arising from the distal sacrum, extending within bone from S2 to the coccyx. There is a large anterior and small posterior extraosseous mass.
Chordoma. Classic appearance of conventional chordoma showing the lobulated architecture with abundant extracellular matrix.
Chordoma. Tumour cells are arranged in cords and nests. Note the typical light basophilic appearance of the myxoid matrix.
Chordoma. Cords of tumour cells with mixed physaliphorous and epithelioid features.
Chordoma. Cytological atypia including multinucleated cells with bizarre nuclei and pseudonuclear inclusion.
Chordoma. Tumour cells arranged in a pseudoalveolar pattern, mimicking renal cell carcinoma.
Chordoma. Nuclear immunoreactivity for brachyury.
Conventional chordoma. Sacrectomy specimen showing a large lobulated mass with a gelatinous appearance, invading and destroying the distal sacrum.
Conventional chordoma. Sagittal CT of the sacrum. There is destruction of the sacrum inferior to S1. Tumour extends proximally within the central spinal canal posterior to S1, the proximal level indicated (arrow). Bone fragments (arrowheads) remain visible anterior and posterior to tumour in the central spinal canal, which is expanded. Distally, there is an anterior extraosseous presacral mass (asterisk).

Q: Macroscopically and microscopically, Dedifferentiated Chordoma typically presents as a biphasic tumor characterized by an abrupt transition from a conventional chordoma to a high-grade [...].
Dedifferentiated chordoma. Typical features of a chordoma (right), with an abrupt change to a high-grade pleomorphic sarcoma showing rhabdomyoblastic differentiation (left).
Deddifferentiated chordoma. Sacrectomy specimen showing a large destructive tumour: the haemorrhagic area represents the conventional component, and the more solid fleshy larger area is a dedifferentiated tumour.
A: spindle and/or pleomorphic sarcoma
Back Extra: Dedifferentiated Chordoma
- Clinical: Deddifferentiated chordoma often presents with rapid progression, pain, and neurological symptoms, and can arise de novo or at a previously resected conventional chordoma site.
- Micro: The hallmark of deddifferentiated chordoma is the presence of conventional chordoma and a high-grade spindle and/or pleomorphic sarcoma, often showing abrupt transitions and possible osteosarcomatous or rhabdomyosarcomatous differentiation.
- Ancillary: The deddifferentiated component of the tumour typically lacks brachyury expression, a marker found in conventional chordoma, as shown by immunohistochemistry.
Reference Gallery:
Dedifferentiated chordoma. Typical features of a chordoma (right), with an abrupt change to a high-grade pleomorphic sarcoma showing rhabdomyoblastic differentiation (left).
Deddifferentiated chordoma. Rhabdomyosarcomatous differentiation highlighted by desmin immunostain. The tumour was also positive for myogenin (not shown).
Deddifferentiated chordoma. Axial T2-weighted MRI of the pelvis shows a biphasic tumour. A large, heterogeneous, hyperintense mass has destroyed the sacrum (asterisk) and extended into the presacral space. Within the anterior aspect of the mass, there is a well-defined, relatively hypointense component (arrows) consistent with dedifferentiated tumour (high-grade pleomorphic spindle cell sarcoma showing smooth muscle differentiation).
Deddifferentiated chordoma. Sacrectomy specimen showing a large destructive tumour: the haemorrhagic area represents the conventional component, and the more solid fleshy larger area is a dedifferentiated tumour.
Deddifferentiated chordoma. Immunoreactivity to brachyury is lost in the dedifferentiated component (left).

Q: In Dedifferentiated Chordoma, the high-grade dedifferentiated component characteristically demonstrates a loss of [...] expression on immunohistochemistry, a marker that is retained in the conventional component.
Deddifferentiated chordoma. Immunoreactivity to brachyury is lost in the dedifferentiated component (left).
A: brachyury
Back Extra: Dedifferentiated Chordoma
- Clinical: Deddifferentiated chordoma often presents with rapid progression, pain, and neurological symptoms, and can arise de novo or at a previously resected conventional chordoma site.
- Micro: The hallmark of deddifferentiated chordoma is the presence of conventional chordoma and a high-grade spindle and/or pleomorphic sarcoma, often showing abrupt transitions and possible osteosarcomatous or rhabdomyosarcomatous differentiation.
- Ancillary: The deddifferentiated component of the tumour typically lacks brachyury expression, a marker found in conventional chordoma, as shown by immunohistochemistry.
Reference Gallery:
Dedifferentiated chordoma. Typical features of a chordoma (right), with an abrupt change to a high-grade pleomorphic sarcoma showing rhabdomyoblastic differentiation (left).
Deddifferentiated chordoma. Rhabdomyosarcomatous differentiation highlighted by desmin immunostain. The tumour was also positive for myogenin (not shown).
Deddifferentiated chordoma. Axial T2-weighted MRI of the pelvis shows a biphasic tumour. A large, heterogeneous, hyperintense mass has destroyed the sacrum (asterisk) and extended into the presacral space. Within the anterior aspect of the mass, there is a well-defined, relatively hypointense component (arrows) consistent with dedifferentiated tumour (high-grade pleomorphic spindle cell sarcoma showing smooth muscle differentiation).
Deddifferentiated chordoma. Sacrectomy specimen showing a large destructive tumour: the haemorrhagic area represents the conventional component, and the more solid fleshy larger area is a dedifferentiated tumour.
Deddifferentiated chordoma. Immunoreactivity to brachyury is lost in the dedifferentiated component (left).

Q: The high-grade sarcomatous component of Dedifferentiated Chordoma may exhibit heterologous elements, most notably osteosarcomatous or [...] differentiation.
Deddifferentiated chordoma. Rhabdomyosarcomatous differentiation highlighted by desmin immunostain. The tumour was also positive for myogenin (not shown).
Deddifferentiated chordoma. Axial T2-weighted MRI of the pelvis shows a biphasic tumour. A large, heterogeneous, hyperintense mass has destroyed the sacrum (asterisk) and extended into the presacral space. Within the anterior aspect of the mass, there is a well-defined, relatively hypointense component (arrows) consistent with dedifferentiated tumour (high-grade pleomorphic spindle cell sarcoma showing smooth muscle differentiation).
A: rhabdomyosarcomatous
Back Extra: Dedifferentiated Chordoma
- Clinical: Deddifferentiated chordoma often presents with rapid progression, pain, and neurological symptoms, and can arise de novo or at a previously resected conventional chordoma site.
- Micro: The hallmark of deddifferentiated chordoma is the presence of conventional chordoma and a high-grade spindle and/or pleomorphic sarcoma, often showing abrupt transitions and possible osteosarcomatous or rhabdomyosarcomatous differentiation.
- Ancillary: The deddifferentiated component of the tumour typically lacks brachyury expression, a marker found in conventional chordoma, as shown by immunohistochemistry.
Reference Gallery:
Dedifferentiated chordoma. Typical features of a chordoma (right), with an abrupt change to a high-grade pleomorphic sarcoma showing rhabdomyoblastic differentiation (left).
Deddifferentiated chordoma. Rhabdomyosarcomatous differentiation highlighted by desmin immunostain. The tumour was also positive for myogenin (not shown).
Deddifferentiated chordoma. Axial T2-weighted MRI of the pelvis shows a biphasic tumour. A large, heterogeneous, hyperintense mass has destroyed the sacrum (asterisk) and extended into the presacral space. Within the anterior aspect of the mass, there is a well-defined, relatively hypointense component (arrows) consistent with dedifferentiated tumour (high-grade pleomorphic spindle cell sarcoma showing smooth muscle differentiation).
Deddifferentiated chordoma. Sacrectomy specimen showing a large destructive tumour: the haemorrhagic area represents the conventional component, and the more solid fleshy larger area is a dedifferentiated tumour.
Deddifferentiated chordoma. Immunoreactivity to brachyury is lost in the dedifferentiated component (left).

Q: A key diagnostic immunohistochemical feature of Poorly Differentiated Chordoma is the characteristic loss of [...] expression.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating lack of staining for (i.e. loss of) SMARCB1 (INI1).
A: SMARCB1 (INI1)
Poorly Differentiated Chordoma
- Clinical: Patients with poorly differentiated chordoma often present with nonspecific symptoms such as headache, pain, cranial nerve symptoms, and weight loss.
- Micro: Poorly differentiated chordoma is composed of cohesive sheets or nests of epithelioid cells with eosinophilic cytoplasm, prominent nucleoli, and geographical necrosis.
- Ancillary: A diagnostic feature of poorly differentiated chordoma is the loss of SMARCB1 (INI1) expression, which can be confirmed by immunohistochemistry.
Reference Gallery:
Poorly differentiated chordoma. The tumour is composed of sheets of poorly differentiated epithelioid cells with eosinophilic cytoplasm, irregular nuclei, and prominent nucleoli. There is a central area of necrosis, but no myxoid stroma is present.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating diffuse immunohistochemical staining for keratin.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating diffuse immunohistochemical nuclear staining for brachyury.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating lack of staining for (i.e. loss of) SMARCB1 (INI1).
Poorly differentiated chordoma. Axial T2-weighted image showing a large enhancing tumour arising in the skull base.

Q: Despite its atypical morphology and loss of INI1, Poorly Differentiated Chordoma retains diffuse nuclear immunohistochemical staining for [...], confirming its notochordal origin.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating diffuse immunohistochemical nuclear staining for brachyury.
A: brachyury
Poorly Differentiated Chordoma
- Clinical: Patients with poorly differentiated chordoma often present with nonspecific symptoms such as headache, pain, cranial nerve symptoms, and weight loss.
- Micro: Poorly differentiated chordoma is composed of cohesive sheets or nests of epithelioid cells with eosinophilic cytoplasm, prominent nucleoli, and geographical necrosis.
- Ancillary: A diagnostic feature of poorly differentiated chordoma is the loss of SMARCB1 (INI1) expression, which can be confirmed by immunohistochemistry.
Reference Gallery:
Poorly differentiated chordoma. The tumour is composed of sheets of poorly differentiated epithelioid cells with eosinophilic cytoplasm, irregular nuclei, and prominent nucleoli. There is a central area of necrosis, but no myxoid stroma is present.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating diffuse immunohistochemical staining for keratin.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating diffuse immunohistochemical nuclear staining for brachyury.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating lack of staining for (i.e. loss of) SMARCB1 (INI1).
Poorly differentiated chordoma. Axial T2-weighted image showing a large enhancing tumour arising in the skull base.

Q: A highly aggressive skull base tumor characterized by cohesive nests of epithelioid cells, prominent nucleoli, geographical necrosis, and an absence of myxoid stroma is known as [...].
Poorly differentiated chordoma. The tumour is composed of sheets of poorly differentiated epithelioid cells with eosinophilic cytoplasm, irregular nuclei, and prominent nucleoli. There is a central area of necrosis, but no myxoid stroma is present.
Poorly differentiated chordoma. Axial T2-weighted image showing a large enhancing tumour arising in the skull base.
A: Poorly Differentiated Chordoma
Poorly Differentiated Chordoma
- Clinical: Patients with poorly differentiated chordoma often present with nonspecific symptoms such as headache, pain, cranial nerve symptoms, and weight loss.
- Micro: Poorly differentiated chordoma is composed of cohesive sheets or nests of epithelioid cells with eosinophilic cytoplasm, prominent nucleoli, and geographical necrosis.
- Ancillary: A diagnostic feature of poorly differentiated chordoma is the loss of SMARCB1 (INI1) expression, which can be confirmed by immunohistochemistry.
Reference Gallery:
Poorly differentiated chordoma. The tumour is composed of sheets of poorly differentiated epithelioid cells with eosinophilic cytoplasm, irregular nuclei, and prominent nucleoli. There is a central area of necrosis, but no myxoid stroma is present.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating diffuse immunohistochemical staining for keratin.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating diffuse immunohistochemical nuclear staining for brachyury.
Poorly differentiated chordoma. Poorly differentiated chordoma demonstrating lack of staining for (i.e. loss of) SMARCB1 (INI1).
Poorly differentiated chordoma. Axial T2-weighted image showing a large enhancing tumour arising in the skull base.

Q: Clinically and radiographically, Osteoblastoma frequently arises in the [...] of the spine and presents with pain that is typically not relieved by NSAIDs.
Osteoblastoma. Axial CT shows an expansile tumour in the posterior elements, with matrix mineralization.
A: posterior elements
Osteoblastoma
- Clinical: Osteoblastoma is characterized by pain, often not relieved by NSAIDs, and can present with neurological symptoms if in the spine. Systemic symptoms can occur in rare cases.
- Micro: Osteoblastoma is composed of interconnecting trabeculae of woven bone rimmed by plump osteoblasts, with a richly vascularized stroma and scattered osteoclast-like giant cells.
- Ancillary: FOS gene rearrangement is found in the majority of osteoblastomas, helping in the diagnosis.
Reference Gallery:
Osteoblastoma. Axial CT shows an expansile tumour in the posterior elements, with matrix mineralization.
Osteoblastoma. Sagittal short-tau inversion recovery (STIR) MRI showing a well-defined lesion with hyperintense oedema-like signal in the adjacent marrow and soft tissue.
Osteoblastoma. Well-defined tumour borders. The tumour is focally merging with remodelled bone at the periphery (maturation).
Osteoblastoma. Woven bone trabeculae lined by one or more layers of plump osteoblasts, scattered osteoclast-type giant cells, and intervening vascular stroma. Anaplasia and atypical mitotic figures are absent.
Osteoblastoma. Interconnecting trabeculae of woven bone rimmed by plump osteoblasts. Richly vascularized fibroblastic stroma.
Osteoblastoma. Nuclear expression of FOS (c-FOS), highlighting the osteoblastic cells.
Osteoblastoma. Osteoblastoma with extensive sclerosis.
Epithelioid osteoblastoma. The lesion is composed of sheets of large, epithelioid osteoblasts associated with bone formation.

Q: Histologically, Osteoblastoma is composed of interconnecting trabeculae of woven bone that are characteristically rimmed by [...] within a richly vascularized stroma.
Osteoblastoma. Woven bone trabeculae lined by one or more layers of plump osteoblasts, scattered osteoclast-type giant cells, and intervening vascular stroma. Anaplasia and atypical mitotic figures are absent.
Osteoblastoma. Interconnecting trabeculae of woven bone rimmed by plump osteoblasts. Richly vascularized fibroblastic stroma.
A: plump osteoblasts
Osteoblastoma
- Clinical: Osteoblastoma is characterized by pain, often not relieved by NSAIDs, and can present with neurological symptoms if in the spine. Systemic symptoms can occur in rare cases.
- Micro: Osteoblastoma is composed of interconnecting trabeculae of woven bone rimmed by plump osteoblasts, with a richly vascularized stroma and scattered osteoclast-like giant cells.
- Ancillary: FOS gene rearrangement is found in the majority of osteoblastomas, helping in the diagnosis.
Reference Gallery:
Osteoblastoma. Axial CT shows an expansile tumour in the posterior elements, with matrix mineralization.
Osteoblastoma. Sagittal short-tau inversion recovery (STIR) MRI showing a well-defined lesion with hyperintense oedema-like signal in the adjacent marrow and soft tissue.
Osteoblastoma. Well-defined tumour borders. The tumour is focally merging with remodelled bone at the periphery (maturation).
Osteoblastoma. Woven bone trabeculae lined by one or more layers of plump osteoblasts, scattered osteoclast-type giant cells, and intervening vascular stroma. Anaplasia and atypical mitotic figures are absent.
Osteoblastoma. Interconnecting trabeculae of woven bone rimmed by plump osteoblasts. Richly vascularized fibroblastic stroma.
Osteoblastoma. Nuclear expression of FOS (c-FOS), highlighting the osteoblastic cells.
Osteoblastoma. Osteoblastoma with extensive sclerosis.
Epithelioid osteoblastoma. The lesion is composed of sheets of large, epithelioid osteoblasts associated with bone formation.

Q: The majority of cases of Osteoblastoma harbor a rearrangement in the [...] gene, which can be highlighted by nuclear immunohistochemical staining.
Osteoblastoma. Nuclear expression of FOS (c-FOS), highlighting the osteoblastic cells.
A: FOS
Osteoblastoma
- Clinical: Osteoblastoma is characterized by pain, often not relieved by NSAIDs, and can present with neurological symptoms if in the spine. Systemic symptoms can occur in rare cases.
- Micro: Osteoblastoma is composed of interconnecting trabeculae of woven bone rimmed by plump osteoblasts, with a richly vascularized stroma and scattered osteoclast-like giant cells.
- Ancillary: FOS gene rearrangement is found in the majority of osteoblastomas, helping in the diagnosis.
Reference Gallery:
Osteoblastoma. Axial CT shows an expansile tumour in the posterior elements, with matrix mineralization.
Osteoblastoma. Sagittal short-tau inversion recovery (STIR) MRI showing a well-defined lesion with hyperintense oedema-like signal in the adjacent marrow and soft tissue.
Osteoblastoma. Well-defined tumour borders. The tumour is focally merging with remodelled bone at the periphery (maturation).
Osteoblastoma. Woven bone trabeculae lined by one or more layers of plump osteoblasts, scattered osteoclast-type giant cells, and intervening vascular stroma. Anaplasia and atypical mitotic figures are absent.
Osteoblastoma. Interconnecting trabeculae of woven bone rimmed by plump osteoblasts. Richly vascularized fibroblastic stroma.
Osteoblastoma. Nuclear expression of FOS (c-FOS), highlighting the osteoblastic cells.
Osteoblastoma. Osteoblastoma with extensive sclerosis.
Epithelioid osteoblastoma. The lesion is composed of sheets of large, epithelioid osteoblasts associated with bone formation.

Q: On imaging, Osteoid Osteoma classically presents as a small, radiolucent central [...] that is surrounded by thick reactive cortical sclerosis.
Osteoid osteoma. Frontal radiograph of the femur demonstrates cortical thickening and sclerosis of the medial femoral shaft.
Osteoid osteoma. Axial CT showing a small nidus with central calcification, surrounded by diffuse sclerosis and cortical thickening.
A: nidus
Back Extra: Osteoid Osteoma
- Clinical: Osteoid osteoma often presents with nocturnal pain that can be relieved by NSAIDs, and is commonly located in the long bones, particularly the femur and tibia.
- Micro: The central nidus of an osteoid osteoma is characterized by well-defined trabeculae of woven bone surrounded by hypervascular sclerotic bone.
- Ancillary: FOS gene rearrangement and elevated prostaglandins (PGE2, PGI2, COX-2) are associated with osteoid osteoma, explaining the pain and sensitivity to NSAIDs.
Reference Gallery:
Osteoid osteoma. Frontal radiograph of the femur demonstrates cortical thickening and sclerosis of the medial femoral shaft.
Osteoid osteoma. Axial CT showing a small nidus with central calcification, surrounded by diffuse sclerosis and cortical thickening.
Osteoid osteoma. Well-defined nidus surrounded by dense cortical / compact lamellar bone.
Osteoid osteoma. Anastomosing trabeculae of woven bone rimmed by plump osteoblasts in a highly vascular background with numerous osteoclast-like giant cells.
Osteoid osteoma. A very sharp circumscription of nidus near the cortical surface showing dense cortex to the right and reactive neocortex to the left of the lesion.

Q: Histologically, the central core of an Osteoid Osteoma is highly vascular and composed of anastomosing trabeculae of [...] prominently rimmed by plump osteoblasts.
Osteoid osteoma. Anastomosing trabeculae of woven bone rimmed by plump osteoblasts in a highly vascular background with numerous osteoclast-like giant cells.
Osteoid osteoma. A very sharp circumscription of nidus near the cortical surface showing dense cortex to the right and reactive neocortex to the left of the lesion.
A: woven bone
Back Extra: Osteoid Osteoma
- Clinical: Osteoid osteoma often presents with nocturnal pain that can be relieved by NSAIDs, and is commonly located in the long bones, particularly the femur and tibia.
- Micro: The central nidus of an osteoid osteoma is characterized by well-defined trabeculae of woven bone surrounded by hypervascular sclerotic bone.
- Ancillary: FOS gene rearrangement and elevated prostaglandins (PGE2, PGI2, COX-2) are associated with osteoid osteoma, explaining the pain and sensitivity to NSAIDs.
Reference Gallery:
Osteoid osteoma. Frontal radiograph of the femur demonstrates cortical thickening and sclerosis of the medial femoral shaft.
Osteoid osteoma. Axial CT showing a small nidus with central calcification, surrounded by diffuse sclerosis and cortical thickening.
Osteoid osteoma. Well-defined nidus surrounded by dense cortical / compact lamellar bone.
Osteoid osteoma. Anastomosing trabeculae of woven bone rimmed by plump osteoblasts in a highly vascular background with numerous osteoclast-like giant cells.
Osteoid osteoma. A very sharp circumscription of nidus near the cortical surface showing dense cortex to the right and reactive neocortex to the left of the lesion.

Q: Clinically, the intense nocturnal pain associated with Osteoid Osteoma is classically relieved by [...] due to the high local production of prostaglandins (e.g., PGE2) by the tumor.
Osteoid osteoma. Axial CT showing a small nidus with central calcification, surrounded by diffuse sclerosis and cortical thickening.
A: NSAIDs
Back Extra: Osteoid Osteoma
- Clinical: Osteoid osteoma often presents with nocturnal pain that can be relieved by NSAIDs, and is commonly located in the long bones, particularly the femur and tibia.
- Micro: The central nidus of an osteoid osteoma is characterized by well-defined trabeculae of woven bone surrounded by hypervascular sclerotic bone.
- Ancillary: FOS gene rearrangement and elevated prostaglandins (PGE2, PGI2, COX-2) are associated with osteoid osteoma, explaining the pain and sensitivity to NSAIDs.
Reference Gallery:
Osteoid osteoma. Frontal radiograph of the femur demonstrates cortical thickening and sclerosis of the medial femoral shaft.
Osteoid osteoma. Axial CT showing a small nidus with central calcification, surrounded by diffuse sclerosis and cortical thickening.
Osteoid osteoma. Well-defined nidus surrounded by dense cortical / compact lamellar bone.
Osteoid osteoma. Anastomosing trabeculae of woven bone rimmed by plump osteoblasts in a highly vascular background with numerous osteoclast-like giant cells.
Osteoid osteoma. A very sharp circumscription of nidus near the cortical surface showing dense cortex to the right and reactive neocortex to the left of the lesion.

Q: Histologically, an Osteoma is a well-demarcated tumor predominantly composed of mature [...] bone, occasionally with cancellous areas and a well-vascularized stroma.
Osteoma. Well-demarcated tumour composed of trabecular bone.
Osteoma. Osteoma of the frontal sinus. The tumour is composed of lamellar/cortical-type bone adjacent to sinus epithelium.
A: lamellar/cortical-type
Back Extra: Osteoma
- Clinical: Osteomas are usually slow-growing and asymptomatic, but they can cause pain, headache, and obstruction of the paranasal sinuses.
- Micro: Osteomas are predominantly composed of mature lamellar/cortical-type bone, with occasional cancellous areas and a well-vascularized stroma.
- Ancillary: CT density measurements can be used to distinguish osteomas from sclerotic metastases, using a cut-off point of > 885 Hounsfield units.
Reference Gallery:
Osteoma of the right frontal sinus. A Frontal radiograph. B Sagittal reformatted CT demonstrating an ossified mass arising on the surface of bone.
Osteoma. Well-demarcated tumour composed of trabecular bone.
Osteoma. Osteoma of the frontal sinus. The tumour is composed of lamellar/cortical-type bone adjacent to sinus epithelium.
Osteoma. Axial CT showing an osteoma of the right mandibular angle (arrow). The tumour is arising on the surface of the bone and is homogeneously dense.
Bone island. Axial CT shows an intramedullary dense bone island involving the coracoid process.
Bone island / enostosis. Low-power image of a bone island involving the medullary cavity of the proximal femur. The lesion is composed of lamellar/cortical-type bone that merges with the surrounding trabecular bone.

Q: Radiologically, an Osteoma presents as a homogeneously dense, slow-growing, ossified mass arising on the surface of bones, frequently involving the craniofacial region such as the mandible and [...] (where it may cause obstruction).
Osteoma of the right frontal sinus. A Frontal radiograph. B Sagittal reformatted CT demonstrating an ossified mass arising on the surface of bone.
Osteoma. Axial CT showing an osteoma of the right mandibular angle (arrow). The tumour is arising on the surface of the bone and is homogeneously dense.
A: paranasal sinuses
Back Extra: Osteoma
- Clinical: Osteomas are usually slow-growing and asymptomatic, but they can cause pain, headache, and obstruction of the paranasal sinuses.
- Micro: Osteomas are predominantly composed of mature lamellar/cortical-type bone, with occasional cancellous areas and a well-vascularized stroma.
- Ancillary: CT density measurements can be used to distinguish osteomas from sclerotic metastases, using a cut-off point of > 885 Hounsfield units.
Reference Gallery:
Osteoma of the right frontal sinus. A Frontal radiograph. B Sagittal reformatted CT demonstrating an ossified mass arising on the surface of bone.
Osteoma. Well-demarcated tumour composed of trabecular bone.
Osteoma. Osteoma of the frontal sinus. The tumour is composed of lamellar/cortical-type bone adjacent to sinus epithelium.
Osteoma. Axial CT showing an osteoma of the right mandibular angle (arrow). The tumour is arising on the surface of the bone and is homogeneously dense.
Bone island. Axial CT shows an intramedullary dense bone island involving the coracoid process.
Bone island / enostosis. Low-power image of a bone island involving the medullary cavity of the proximal femur. The lesion is composed of lamellar/cortical-type bone that merges with the surrounding trabecular bone.

Q: Histologically, High-grade surface osteosarcoma is characterized by malignant polyhedral and spindle cells that produce a characteristic lace-like [...] matrix.
High-grade surface osteosarcoma. The histology is typical of high-grade osteoblastic osteosarcoma, with malignant-appearing polyhedral and spindle cells producing an immature osteoid matrix with a lace-like pattern. Note the abundant mitoses.
A: immature osteoid
Back Extra: High-grade surface osteosarcoma
- Clinical: High-grade surface osteosarcoma typically presents with swelling and pain of short duration.
- Micro: Histologically, it is identical to high-grade conventional osteosarcoma, with malignant polyhedral and spindle cells producing an immature osteoid matrix.
- Ancillary: No clinically relevant ancillary studies are typically required for diagnosis.
Reference Gallery:
High-grade surface osteosarcoma. Lateral radiograph of the right tibia and fibula. An elliptical mass is projected adjacent to the tibial bone surface, showing fairly dense lobular and punctate mineralization. No cortical destruction is identified.
High-grade surface osteosarcoma. Gross specimen sectioned axially demonstrates a large tumour mass extending from the bone surface to the skin. The cortex and medullary cavity are not involved. The tumour has a heterogeneous appearance, ranging from densely ossified to fleshy.
High-grade surface osteosarcoma. The histology is typical of high-grade osteoblastic osteosarcoma, with malignant-appearing polyhedral and spindle cells producing an immature osteoid matrix with a lace-like pattern. Note the abundant mitoses.
High-grade surface osteosarcoma. Axial T1-weighted MRI of the right proximal calf. A lobular mass is located on the subcutaneous surface of the tibia. It causes cortical thinning, invades adjacent muscle, extends into the subcutaneous fat, and fungates through the skin. Lobular low signal in the deep aspect of the mass is consistent with ossification.

Q: On imaging and gross examination, High-grade surface osteosarcoma typically presents as a densely ossified surface-based bone tumor that characteristically lacks involvement of the underlying [...].
High-grade surface osteosarcoma. Lateral radiograph of the right tibia and fibula. An elliptical mass is projected adjacent to the tibial bone surface, showing fairly dense lobular and punctate mineralization. No cortical destruction is identified.
High-grade surface osteosarcoma. Gross specimen sectioned axially demonstrates a large tumour mass extending from the bone surface to the skin. The cortex and medullary cavity are not involved. The tumour has a heterogeneous appearance, ranging from densely ossified to fleshy.
A: medullary cavity
Back Extra: High-grade surface osteosarcoma
- Clinical: High-grade surface osteosarcoma typically presents with swelling and pain of short duration.
- Micro: Histologically, it is identical to high-grade conventional osteosarcoma, with malignant polyhedral and spindle cells producing an immature osteoid matrix.
- Ancillary: No clinically relevant ancillary studies are typically required for diagnosis.
Reference Gallery:
High-grade surface osteosarcoma. Lateral radiograph of the right tibia and fibula. An elliptical mass is projected adjacent to the tibial bone surface, showing fairly dense lobular and punctate mineralization. No cortical destruction is identified.
High-grade surface osteosarcoma. Gross specimen sectioned axially demonstrates a large tumour mass extending from the bone surface to the skin. The cortex and medullary cavity are not involved. The tumour has a heterogeneous appearance, ranging from densely ossified to fleshy.
High-grade surface osteosarcoma. The histology is typical of high-grade osteoblastic osteosarcoma, with malignant-appearing polyhedral and spindle cells producing an immature osteoid matrix with a lace-like pattern. Note the abundant mitoses.
High-grade surface osteosarcoma. Axial T1-weighted MRI of the right proximal calf. A lobular mass is located on the subcutaneous surface of the tibia. It causes cortical thinning, invades adjacent muscle, extends into the subcutaneous fat, and fungates through the skin. Lobular low signal in the deep aspect of the mass is consistent with ossification.

Q: Microscopically, low-grade central osteosarcoma consists of mildly cellular fascicles of spindle cells producing well-formed, irregular [...] that can closely resemble fibrous dysplasia.
Low-grade central osteosarcoma. Low-power view showing a mildly cellular fascicular proliferation of spindle cells, admixed with well-formed neoplastic bone trabeculae in a parallel distribution.
Low-grade central osteosarcoma. Some tumours produce well-formed but irregular bone trabeculae, reminiscent of fibrous dysplasia.
A: bony trabeculae
Back Extra: Low-grade central osteosarcoma
- Clinical: Low-grade central osteosarcoma often presents with swelling or pain and can have a prolonged preoperative period (average > 2 years).
- Micro: The tumour is composed of mildly cellular fascicles of spindle cells with mild nuclear atypia and well-formed, irregular bony trabeculae.
- Ancillary: MDM2 amplification is a helpful diagnostic marker to differentiate low-grade central osteosarcoma from benign mimics.
Reference Gallery:
Low-grade central osteosarcoma. Frontal radiograph of the hip demonstrates an ill-defined lytic and sclerotic lesion with coarsened trabeculations in the proximal femoral metaphysis.
Low-grade central osteosarcoma with focal dedifferentiation. A large lytic and sclerotic lesion with trabeculation in the distal femoral metaphysis, extending to the end of the bone. The tumour margin is partly well defined, and bone cortex is mildly expanded. Cloud-like soft tissue density represents a dedifferentiated component.
Low-grade central osteosarcoma. Bisected resection specimen of the proximal femur showing a fibrous tumour with focal gritty areas and cortical expansion.
Low-grade central osteosarcoma. Low-power view showing a mildly cellular fascicular proliferation of spindle cells, admixed with well-formed neoplastic bone trabeculae in a parallel distribution.
Low-grade central osteosarcoma. Some tumours produce well-formed but irregular bone trabeculae, reminiscent of fibrous dysplasia.
Low-grade central osteosarcoma. Some tumours focally lack matrix production, resembling desmoplastic fibroma.
Low-grade central osteosarcoma. Tumour spindle cells display mild nuclear atypia.
Dedifferentiated low-grade central osteosarcoma. Low-grade central osteosarcoma (left half) progresses (dedifferentiates) to high-grade sarcoma (right half) with greater degrees of cellularity and nuclear atypia.
Low-grade central osteosarcoma. FISH shows MDM2 amplification in tumour cells. Green, MDM2; red, CEN12.

Q: In low-grade central osteosarcoma, detecting the amplification of [...] via FISH is highly useful to differentiate this tumor from benign mimics.
Low-grade central osteosarcoma. FISH shows MDM2 amplification in tumour cells. Green, MDM2; red, CEN12.
A: MDM2
Back Extra: Low-grade central osteosarcoma
- Clinical: Low-grade central osteosarcoma often presents with swelling or pain and can have a prolonged preoperative period (average > 2 years).
- Micro: The tumour is composed of mildly cellular fascicles of spindle cells with mild nuclear atypia and well-formed, irregular bony trabeculae.
- Ancillary: MDM2 amplification is a helpful diagnostic marker to differentiate low-grade central osteosarcoma from benign mimics.
Reference Gallery:
Low-grade central osteosarcoma. Frontal radiograph of the hip demonstrates an ill-defined lytic and sclerotic lesion with coarsened trabeculations in the proximal femoral metaphysis.
Low-grade central osteosarcoma with focal dedifferentiation. A large lytic and sclerotic lesion with trabeculation in the distal femoral metaphysis, extending to the end of the bone. The tumour margin is partly well defined, and bone cortex is mildly expanded. Cloud-like soft tissue density represents a dedifferentiated component.
Low-grade central osteosarcoma. Bisected resection specimen of the proximal femur showing a fibrous tumour with focal gritty areas and cortical expansion.
Low-grade central osteosarcoma. Low-power view showing a mildly cellular fascicular proliferation of spindle cells, admixed with well-formed neoplastic bone trabeculae in a parallel distribution.
Low-grade central osteosarcoma. Some tumours produce well-formed but irregular bone trabeculae, reminiscent of fibrous dysplasia.
Low-grade central osteosarcoma. Some tumours focally lack matrix production, resembling desmoplastic fibroma.
Low-grade central osteosarcoma. Tumour spindle cells display mild nuclear atypia.
Dedifferentiated low-grade central osteosarcoma. Low-grade central osteosarcoma (left half) progresses (dedifferentiates) to high-grade sarcoma (right half) with greater degrees of cellularity and nuclear atypia.
Low-grade central osteosarcoma. FISH shows MDM2 amplification in tumour cells. Green, MDM2; red, CEN12.

Q: Low-grade central osteosarcoma can undergo focal [...], an abrupt transition into a high-grade sarcoma characterized by markedly increased cellularity and nuclear atypia.
Low-grade central osteosarcoma with focal dedifferentiation. A large lytic and sclerotic lesion with trabeculation in the distal femoral metaphysis, extending to the end of the bone. The tumour margin is partly well defined, and bone cortex is mildly expanded. Cloud-like soft tissue density represents a dedifferentiated component.
Dedifferentiated low-grade central osteosarcoma. Low-grade central osteosarcoma (left half) progresses (dedifferentiates) to high-grade sarcoma (right half) with greater degrees of cellularity and nuclear atypia.
A: dedifferentiation
Back Extra: Low-grade central osteosarcoma
- Clinical: Low-grade central osteosarcoma often presents with swelling or pain and can have a prolonged preoperative period (average > 2 years).
- Micro: The tumour is composed of mildly cellular fascicles of spindle cells with mild nuclear atypia and well-formed, irregular bony trabeculae.
- Ancillary: MDM2 amplification is a helpful diagnostic marker to differentiate low-grade central osteosarcoma from benign mimics.
Reference Gallery:
Low-grade central osteosarcoma. Frontal radiograph of the hip demonstrates an ill-defined lytic and sclerotic lesion with coarsened trabeculations in the proximal femoral metaphysis.
Low-grade central osteosarcoma with focal dedifferentiation. A large lytic and sclerotic lesion with trabeculation in the distal femoral metaphysis, extending to the end of the bone. The tumour margin is partly well defined, and bone cortex is mildly expanded. Cloud-like soft tissue density represents a dedifferentiated component.
Low-grade central osteosarcoma. Bisected resection specimen of the proximal femur showing a fibrous tumour with focal gritty areas and cortical expansion.
Low-grade central osteosarcoma. Low-power view showing a mildly cellular fascicular proliferation of spindle cells, admixed with well-formed neoplastic bone trabeculae in a parallel distribution.
Low-grade central osteosarcoma. Some tumours produce well-formed but irregular bone trabeculae, reminiscent of fibrous dysplasia.
Low-grade central osteosarcoma. Some tumours focally lack matrix production, resembling desmoplastic fibroma.
Low-grade central osteosarcoma. Tumour spindle cells display mild nuclear atypia.
Dedifferentiated low-grade central osteosarcoma. Low-grade central osteosarcoma (left half) progresses (dedifferentiates) to high-grade sarcoma (right half) with greater degrees of cellularity and nuclear atypia.
Low-grade central osteosarcoma. FISH shows MDM2 amplification in tumour cells. Green, MDM2; red, CEN12.

Q: Microscopically, the tumor in Parosteal Osteosarcoma is characterized by well-formed bone trabeculae and spindle cells with minimal atypia that are typically arranged in a [...] pattern.
Parosteal osteosarcoma. Low-power image showing fascicles of spindle cells admixed with well-developed bone trabeculae arranged in a parallel pattern.
Parosteal osteosarcoma. Higher magnification showing spindle cells with mild atypia and bone trabeculae.
A: parallel
Back Extra: Parosteal Osteosarcoma
- Clinical: Patients with parosteal osteosarcoma often present with a painless mass, and a long history of symptoms, typically over a year.
- Micro: The tumour is characterized by well-formed bone trabeculae and spindle cells with minimal atypia, arranged in a parallel pattern.
- Ancillary: FISH analysis for MDM2 amplification is a highly sensitive and specific diagnostic tool for parosteal osteosarcoma.
Reference Gallery:
Parosteal osteosarcoma. Lateral radiograph shows a densely ossified mass attached to the posterior aspect of the distal femur superiorly, separated by a lucent plane inferiorly (arrow).
Parosteal osteosarcoma. Gross appearance (sagittal section) showing the three tumour components: a well-differentiated deep component (1); a large, mineralized overlying mass (2); and the layer of cartilage on the tumour surface (3).
Dedifferentiated parosteal osteosarcoma. The large dedifferentiated, haemorrhagic component is seen inferiorly (1); low-grade ossified tumour is present superiorly (2).
Parosteal osteosarcoma. Low-power image showing fascicles of spindle cells admixed with well-developed bone trabeculae arranged in a parallel pattern.
Parosteal osteosarcoma. Irregular anastomosing and curved bone trabeculae in parosteal osteosarcoma simulating fibrous dysplasia.
Parosteal osteosarcoma. Higher magnification showing spindle cells with mild atypia and bone trabeculae.
Parosteal osteosarcoma. Cartilage cap in parosteal osteosarcoma.
Parosteal osteosarcoma. Cartilaginous differentiation in parosteal osteosarcoma.
Parosteal osteosarcoma. Diffuse nuclear staining for MDM2.
Parosteal osteosarcoma. SNP array analysis of a parosteal osteosarcoma shows gain of genomic regions in chromosome 12, including high-level amplification of CDK4 and MDM2.
Parosteal osteosarcoma. Partial metaphase spread from a parosteal osteosarcoma. FISH analysis using probes specific for MDM2 (red) and CDK4 (green) shows that the ring chromosome contains many copies of these genes.
Parosteal osteosarcoma. Axial CT shows a heterogeneous ossified mass with slender attachment to the posterior cortex of the femur. A well-differentiated, relatively lucent component is seen deeply (1) and a lobular, sclerotic mass superficially (2).

Q: Diagnostic ancillary testing for Parosteal Osteosarcoma typically demonstrates high-level amplification of the CDK4 and [...] genes.
Parosteal osteosarcoma. Diffuse nuclear staining for MDM2.
Parosteal osteosarcoma. Partial metaphase spread from a parosteal osteosarcoma. FISH analysis using probes specific for MDM2 (red) and CDK4 (green) shows that the ring chromosome contains many copies of these genes.
A: MDM2
Back Extra: Parosteal Osteosarcoma
- Clinical: Patients with parosteal osteosarcoma often present with a painless mass, and a long history of symptoms, typically over a year.
- Micro: The tumour is characterized by well-formed bone trabeculae and spindle cells with minimal atypia, arranged in a parallel pattern.
- Ancillary: FISH analysis for MDM2 amplification is a highly sensitive and specific diagnostic tool for parosteal osteosarcoma.
Reference Gallery:
Parosteal osteosarcoma. Lateral radiograph shows a densely ossified mass attached to the posterior aspect of the distal femur superiorly, separated by a lucent plane inferiorly (arrow).
Parosteal osteosarcoma. Gross appearance (sagittal section) showing the three tumour components: a well-differentiated deep component (1); a large, mineralized overlying mass (2); and the layer of cartilage on the tumour surface (3).
Dedifferentiated parosteal osteosarcoma. The large dedifferentiated, haemorrhagic component is seen inferiorly (1); low-grade ossified tumour is present superiorly (2).
Parosteal osteosarcoma. Low-power image showing fascicles of spindle cells admixed with well-developed bone trabeculae arranged in a parallel pattern.
Parosteal osteosarcoma. Irregular anastomosing and curved bone trabeculae in parosteal osteosarcoma simulating fibrous dysplasia.
Parosteal osteosarcoma. Higher magnification showing spindle cells with mild atypia and bone trabeculae.
Parosteal osteosarcoma. Cartilage cap in parosteal osteosarcoma.
Parosteal osteosarcoma. Cartilaginous differentiation in parosteal osteosarcoma.
Parosteal osteosarcoma. Diffuse nuclear staining for MDM2.
Parosteal osteosarcoma. SNP array analysis of a parosteal osteosarcoma shows gain of genomic regions in chromosome 12, including high-level amplification of CDK4 and MDM2.
Parosteal osteosarcoma. Partial metaphase spread from a parosteal osteosarcoma. FISH analysis using probes specific for MDM2 (red) and CDK4 (green) shows that the ring chromosome contains many copies of these genes.
Parosteal osteosarcoma. Axial CT shows a heterogeneous ossified mass with slender attachment to the posterior cortex of the femur. A well-differentiated, relatively lucent component is seen deeply (1) and a lobular, sclerotic mass superficially (2).

Q: Radiologically, Parosteal Osteosarcoma characteristically presents as a densely ossified mass on the posterior distal femur that is separated from the underlying bone cortex by a [...].
Parosteal osteosarcoma. Lateral radiograph shows a densely ossified mass attached to the posterior aspect of the distal femur superiorly, separated by a lucent plane inferiorly (arrow).
Parosteal osteosarcoma. Axial CT shows a heterogeneous ossified mass with slender attachment to the posterior cortex of the femur. A well-differentiated, relatively lucent component is seen deeply (1) and a lobular, sclerotic mass superficially (2).
A: lucent plane
Back Extra: Parosteal Osteosarcoma
- Clinical: Patients with parosteal osteosarcoma often present with a painless mass, and a long history of symptoms, typically over a year.
- Micro: The tumour is characterized by well-formed bone trabeculae and spindle cells with minimal atypia, arranged in a parallel pattern.
- Ancillary: FISH analysis for MDM2 amplification is a highly sensitive and specific diagnostic tool for parosteal osteosarcoma.
Reference Gallery:
Parosteal osteosarcoma. Lateral radiograph shows a densely ossified mass attached to the posterior aspect of the distal femur superiorly, separated by a lucent plane inferiorly (arrow).
Parosteal osteosarcoma. Gross appearance (sagittal section) showing the three tumour components: a well-differentiated deep component (1); a large, mineralized overlying mass (2); and the layer of cartilage on the tumour surface (3).
Dedifferentiated parosteal osteosarcoma. The large dedifferentiated, haemorrhagic component is seen inferiorly (1); low-grade ossified tumour is present superiorly (2).
Parosteal osteosarcoma. Low-power image showing fascicles of spindle cells admixed with well-developed bone trabeculae arranged in a parallel pattern.
Parosteal osteosarcoma. Irregular anastomosing and curved bone trabeculae in parosteal osteosarcoma simulating fibrous dysplasia.
Parosteal osteosarcoma. Higher magnification showing spindle cells with mild atypia and bone trabeculae.
Parosteal osteosarcoma. Cartilage cap in parosteal osteosarcoma.
Parosteal osteosarcoma. Cartilaginous differentiation in parosteal osteosarcoma.
Parosteal osteosarcoma. Diffuse nuclear staining for MDM2.
Parosteal osteosarcoma. SNP array analysis of a parosteal osteosarcoma shows gain of genomic regions in chromosome 12, including high-level amplification of CDK4 and MDM2.
Parosteal osteosarcoma. Partial metaphase spread from a parosteal osteosarcoma. FISH analysis using probes specific for MDM2 (red) and CDK4 (green) shows that the ring chromosome contains many copies of these genes.
Parosteal osteosarcoma. Axial CT shows a heterogeneous ossified mass with slender attachment to the posterior cortex of the femur. A well-differentiated, relatively lucent component is seen deeply (1) and a lobular, sclerotic mass superficially (2).

Q: Histologically, the predominant matrix in periosteal osteosarcoma consists of lobules of cytologically atypical [...], which are separated by bands of primitive sarcomatous cells producing fine, lace-like osteoid.
Periosteal osteosarcoma. Scanning power. This composite photomicrograph demonstrates pale cartilaginous areas with intervening linear arrays of reactive bone coursing through the matrix towards the perimeter. The base is more densely ossified and consists of tumour bone and cartilage matrix. Note the thin layer of periosteum along the surface.
Periosteal osteosarcoma. At higher power, the linear reactive bone spicules are separated by cartilaginous tumour matrix, with focal central lace-like osteoid production.
Periosteal osteosarcoma. Atypical nuclear morphology of the cartilaginous matrix is illustrated and central osteoid formation is present.
A: cartilage
Periosteal Osteosarcoma
- Clinical: Patients with periosteal osteosarcoma often present with swelling and/or pain of short duration (weeks to months).
- Micro: Histopathology of periosteal osteosarcoma shows poorly delineated lobules of cytologically atypical cartilage with intervening bands of primitive sarcomatous cells and bone formation.
- Ancillary: MDM2/CDK4 amplification and IDH mutations are typically not identified in periosteal osteosarcoma.
Reference Gallery:
Periosteal osteosarcoma. Lateral radiograph of the left femur. There is a fusiform mass on the bone surface, showing dense calcification and lobular less-mineralized tumour superficially, within which are irregular bone spicules. The cortex of the femur appears intact.
Periosteal osteosarcoma. Axial T1-weighted (left) and T2-weighted (right) MRI of the left femur. The surface mass incompletely surrounds the bone. It is hyperintense on both sequences, with homogeneous low signal at its base, indicating ossification, and slender hypointense strands, best seen on the T1-weighted image, due to fine bone spicules. The cortex is thinned laterally but not disrupted, and marrow signal is normal.
Periosteal osteosarcoma. Gross specimen, coronal. Pale tumour with visible vertical perpendicular spiculation confined to the surface of the cortex and entirely beneath the periosteum, lending a fusiform architecture. The cortex and medullary cavity are unremarkable.
Periosteal osteosarcoma. Gross specimen, axial. In this section, much of the tumour has a translucent, chondroid appearance. Irregular cream-coloured ossification is visible near the cortex, whereas the spiculated linear appearance predominates at the perimeter. A surface rim of periosteum surrounds the tumour, and the cortex and medulla are intact.
Periosteal osteosarcoma. Scanning power. This composite photomicrograph demonstrates pale cartilaginous areas with intervening linear arrays of reactive bone coursing through the matrix towards the perimeter. The base is more densely ossified and consists of tumour bone and cartilage matrix. Note the thin layer of periosteum along the surface.
Periosteal osteosarcoma. At higher power, the linear reactive bone spicules are separated by cartilaginous tumour matrix, with focal central lace-like osteoid production.
Periosteal osteosarcoma. Atypical nuclear morphology of the cartilaginous matrix is illustrated and central osteoid formation is present.
Periosteal osteosarcoma. Higher power of the tumour periphery demonstrates a tendency of the tumour cells to spindle.

Q: Radiologically and grossly, periosteal osteosarcoma typically presents as a superficial fusiform mass with characteristic perpendicular, radiating [...] and a largely intact underlying cortex.
Periosteal osteosarcoma. Lateral radiograph of the left femur. There is a fusiform mass on the bone surface, showing dense calcification and lobular less-mineralized tumour superficially, within which are irregular bone spicules. The cortex of the femur appears intact.
Periosteal osteosarcoma. Gross specimen, coronal. Pale tumour with visible vertical perpendicular spiculation confined to the surface of the cortex and entirely beneath the periosteum, lending a fusiform architecture. The cortex and medullary cavity are unremarkable.
Periosteal osteosarcoma. Gross specimen, axial. In this section, much of the tumour has a translucent, chondroid appearance. Irregular cream-coloured ossification is visible near the cortex, whereas the spiculated linear appearance predominates at the perimeter. A surface rim of periosteum surrounds the tumour, and the cortex and medulla are intact.
A: bone spicules
Periosteal Osteosarcoma
- Clinical: Patients with periosteal osteosarcoma often present with swelling and/or pain of short duration (weeks to months).
- Micro: Histopathology of periosteal osteosarcoma shows poorly delineated lobules of cytologically atypical cartilage with intervening bands of primitive sarcomatous cells and bone formation.
- Ancillary: MDM2/CDK4 amplification and IDH mutations are typically not identified in periosteal osteosarcoma.
Reference Gallery:
Periosteal osteosarcoma. Lateral radiograph of the left femur. There is a fusiform mass on the bone surface, showing dense calcification and lobular less-mineralized tumour superficially, within which are irregular bone spicules. The cortex of the femur appears intact.
Periosteal osteosarcoma. Axial T1-weighted (left) and T2-weighted (right) MRI of the left femur. The surface mass incompletely surrounds the bone. It is hyperintense on both sequences, with homogeneous low signal at its base, indicating ossification, and slender hypointense strands, best seen on the T1-weighted image, due to fine bone spicules. The cortex is thinned laterally but not disrupted, and marrow signal is normal.
Periosteal osteosarcoma. Gross specimen, coronal. Pale tumour with visible vertical perpendicular spiculation confined to the surface of the cortex and entirely beneath the periosteum, lending a fusiform architecture. The cortex and medullary cavity are unremarkable.
Periosteal osteosarcoma. Gross specimen, axial. In this section, much of the tumour has a translucent, chondroid appearance. Irregular cream-coloured ossification is visible near the cortex, whereas the spiculated linear appearance predominates at the perimeter. A surface rim of periosteum surrounds the tumour, and the cortex and medulla are intact.
Periosteal osteosarcoma. Scanning power. This composite photomicrograph demonstrates pale cartilaginous areas with intervening linear arrays of reactive bone coursing through the matrix towards the perimeter. The base is more densely ossified and consists of tumour bone and cartilage matrix. Note the thin layer of periosteum along the surface.
Periosteal osteosarcoma. At higher power, the linear reactive bone spicules are separated by cartilaginous tumour matrix, with focal central lace-like osteoid production.
Periosteal osteosarcoma. Atypical nuclear morphology of the cartilaginous matrix is illustrated and central osteoid formation is present.
Periosteal osteosarcoma. Higher power of the tumour periphery demonstrates a tendency of the tumour cells to spindle.

Q: The diagnosis of Secondary Osteosarcoma should be strongly suspected when an enlarging, aggressive bone mass develops in a patient with a history of prior radiation therapy or [...] of bone.
Paget osteosarcoma. Axial CT shows multifocal synchronous tumour at presentation. An osteoblastic lesion is present in the right ilium (arrow).
Postirradiation osteosarcoma. Anteroposterior radiograph of the right hemipelvis showing lytic destruction of the right ilium (arrows) and pathological fracture of the acetabulum, with central dislocation of the right hip. Postradiotherapy sclerosis is present in the right ilium after radiotherapy 12 years previously for a gynaecological malignancy.
A: Paget disease
Back Extra: Secondary Osteosarcoma
- Clinical: New pain and an enlarging mass in a patient with a history of predisposing bone conditions such as Paget disease or radiation therapy suggest the diagnosis of secondary osteosarcoma.
- Micro: The histological features of secondary osteosarcoma are indistinguishable from primary osteosarcoma, often showing highly pleomorphic sarcoma with bizarre nuclei and atypical mitoses.
- Ancillary: Ancillary studies in radiation-associated osteosarcoma can reveal mutation signatures of ionizing radiation, including an excess of small deletions and balanced inversions.
Reference Gallery:
Paget osteosarcoma. Axial CT shows multifocal synchronous tumour at presentation. An osteoblastic lesion is present in the right ilium (arrow).
Paget osteosarcoma. The more inferior tumour in the acetabulum is lytic (asterisk). There is background cortical thickening and trabecular coarsening in the pelvis and right proximal femur due to Paget disease.
Postirradiation osteosarcoma. Anteroposterior radiograph of the right hemipelvis showing lytic destruction of the right ilium (arrows) and pathological fracture of the acetabulum, with central dislocation of the right hip. Postradiotherapy sclerosis is present in the right ilium after radiotherapy 12 years previously for a gynaecological malignancy.
Postirradiation osteosarcoma. Coronal T2-weighted MRI of the right hemipelvis. The lytic tumour corresponds to a haemorrhagic mass (asterisk), which has destroyed the acetabulum and infiltrated the ilium and ischium (arrows).
Osteosarcoma in Paget disease of bone. The pre-existing bone shows features of Paget disease: the bone is thickened with mosaic lines of mineralization and is bordered by osteoclasts. A highly pleomorphic sarcoma is present, with bizarre nuclei and atypical mitoses, adjacent to the aberrant bone.
Osteosarcoma arising in infarct. An osteosarcoma (right) arising in a bone affected by infarction (left).
Secondary osteosarcoma. Osteosarcoma arising in association with a total knee prosthesis. The tumour is haemorrhagic and has destroyed the bone.

Q: While the tumor cells themselves are highly pleomorphic and indistinguishable from primary lesions, Secondary Osteosarcoma arising in the setting of Paget disease features adjacent thickened bone demonstrating characteristic [...] of mineralization.
Osteosarcoma in Paget disease of bone. The pre-existing bone shows features of Paget disease: the bone is thickened with mosaic lines of mineralization and is bordered by osteoclasts. A highly pleomorphic sarcoma is present, with bizarre nuclei and atypical mitoses, adjacent to the aberrant bone.
A: mosaic lines
Back Extra: Secondary Osteosarcoma
- Clinical: New pain and an enlarging mass in a patient with a history of predisposing bone conditions such as Paget disease or radiation therapy suggest the diagnosis of secondary osteosarcoma.
- Micro: The histological features of secondary osteosarcoma are indistinguishable from primary osteosarcoma, often showing highly pleomorphic sarcoma with bizarre nuclei and atypical mitoses.
- Ancillary: Ancillary studies in radiation-associated osteosarcoma can reveal mutation signatures of ionizing radiation, including an excess of small deletions and balanced inversions.
Reference Gallery:
Paget osteosarcoma. Axial CT shows multifocal synchronous tumour at presentation. An osteoblastic lesion is present in the right ilium (arrow).
Paget osteosarcoma. The more inferior tumour in the acetabulum is lytic (asterisk). There is background cortical thickening and trabecular coarsening in the pelvis and right proximal femur due to Paget disease.
Postirradiation osteosarcoma. Anteroposterior radiograph of the right hemipelvis showing lytic destruction of the right ilium (arrows) and pathological fracture of the acetabulum, with central dislocation of the right hip. Postradiotherapy sclerosis is present in the right ilium after radiotherapy 12 years previously for a gynaecological malignancy.
Postirradiation osteosarcoma. Coronal T2-weighted MRI of the right hemipelvis. The lytic tumour corresponds to a haemorrhagic mass (asterisk), which has destroyed the acetabulum and infiltrated the ilium and ischium (arrows).
Osteosarcoma in Paget disease of bone. The pre-existing bone shows features of Paget disease: the bone is thickened with mosaic lines of mineralization and is bordered by osteoclasts. A highly pleomorphic sarcoma is present, with bizarre nuclei and atypical mitoses, adjacent to the aberrant bone.
Osteosarcoma arising in infarct. An osteosarcoma (right) arising in a bone affected by infarction (left).
Secondary osteosarcoma. Osteosarcoma arising in association with a total knee prosthesis. The tumour is haemorrhagic and has destroyed the bone.

Q: Radiologic imaging of Chondromesenchymal Hamartoma of Chest Wall typically reveals an expansile lytic rib lesion with an internal [...] and occasionally fluid-fluid levels indicative of intralesional hemorrhage.
Chondromesenchymal hamartoma. Axial CT of a chondromesenchymal hamartoma shows an expansile lytic lesion involving a right posterior rib with internal chondroid matrix (arrow) and an associated extrapleural and posterior soft tissue mass (asterisks).
Chondromesenchymal hamartoma. Sagittal T2-weighted MRI of a 1-year-old girl shows a large mass arising from a posterior rib with a large heterogeneous extrapleural soft tissue mass. The mass is associated with deformity of the adjacent rib (not shown) and contains multiple internal fluid-filled spaces (arrow), some of which contain fluid-fluid levels indicative of intralesional haemorrhage.
A: chondroid matrix
Back Extra: Chondromesenchymal Hamartoma of Chest Wall
- Clinical: Chondromesenchymal hamartoma of chest wall typically presents as a slow-growing palpable mass, most often diagnosed within the first year of life.
- Micro: Histologically, the lesion is characterized by nodules of hyaline cartilage, reactive-appearing bone, bland spindle cells, and multinucleated giant cells.
- Ancillary: No specific ancillary studies are required for diagnosis; imaging studies such as CT and MRI help in characterizing the lesion and planning surgery.
Reference Gallery:
Chondromesenchymal hamartoma. Low-power examination reveals a cystic lesion with nodules of hyaline cartilage.
Chondromesenchymal hamartoma. Nodule of cartilage with an appearance similar to the epiphyseal growth plate.
Chondromesenchymal hamartoma. The cyst walls are composed of a loose arrangement of bland spindled cells and multinucleated giant cells.
Chondromesenchymal hamartoma. Foci of immature bony trabeculae are also present.
Chondromesenchymal hamartoma. Axial CT of a chondromesenchymal hamartoma shows an expansile lytic lesion involving a right posterior rib with internal chondroid matrix (arrow) and an associated extrapleural and posterior soft tissue mass (asterisks).
Chondromesenchymal hamartoma. Sagittal T2-weighted MRI of a 1-year-old girl shows a large mass arising from a posterior rib with a large heterogeneous extrapleural soft tissue mass. The mass is associated with deformity of the adjacent rib (not shown) and contains multiple internal fluid-filled spaces (arrow), some of which contain fluid-fluid levels indicative of intralesional haemorrhage.

Q: Histologically, Chondromesenchymal Hamartoma of Chest Wall is characterized by cyst walls containing bland spindled cells and multinucleated giant cells, which are admixed with reactive bone and prominent nodules of [...].
Chondromesenchymal hamartoma. Low-power examination reveals a cystic lesion with nodules of hyaline cartilage.
Chondromesenchymal hamartoma. The cyst walls are composed of a loose arrangement of bland spindled cells and multinucleated giant cells.
Chondromesenchymal hamartoma. Foci of immature bony trabeculae are also present.
A: hyaline cartilage
Back Extra: Chondromesenchymal Hamartoma of Chest Wall
- Clinical: Chondromesenchymal hamartoma of chest wall typically presents as a slow-growing palpable mass, most often diagnosed within the first year of life.
- Micro: Histologically, the lesion is characterized by nodules of hyaline cartilage, reactive-appearing bone, bland spindle cells, and multinucleated giant cells.
- Ancillary: No specific ancillary studies are required for diagnosis; imaging studies such as CT and MRI help in characterizing the lesion and planning surgery.
Reference Gallery:
Chondromesenchymal hamartoma. Low-power examination reveals a cystic lesion with nodules of hyaline cartilage.
Chondromesenchymal hamartoma. Nodule of cartilage with an appearance similar to the epiphyseal growth plate.
Chondromesenchymal hamartoma. The cyst walls are composed of a loose arrangement of bland spindled cells and multinucleated giant cells.
Chondromesenchymal hamartoma. Foci of immature bony trabeculae are also present.
Chondromesenchymal hamartoma. Axial CT of a chondromesenchymal hamartoma shows an expansile lytic lesion involving a right posterior rib with internal chondroid matrix (arrow) and an associated extrapleural and posterior soft tissue mass (asterisks).
Chondromesenchymal hamartoma. Sagittal T2-weighted MRI of a 1-year-old girl shows a large mass arising from a posterior rib with a large heterogeneous extrapleural soft tissue mass. The mass is associated with deformity of the adjacent rib (not shown) and contains multiple internal fluid-filled spaces (arrow), some of which contain fluid-fluid levels indicative of intralesional haemorrhage.

Q: A highly characteristic histologic feature of Fibrocartilaginous Mesenchymoma is the presence of hyaline cartilage nodules that undergo enchondral ossification, frequently resembling an [...].
Fibrocartilaginous mesenchymoma. Enchondral ossification with bone formation at one edge of a cartilagenous nodule.
Fibrocartilaginous mesenchymoma. Epiphyseal growth plate–like cartilaginous nodule in a spindle cell proliferation.
A: epiphyseal growth plate
Back Extra: Fibrocartilaginous Mesenchymoma
- Clinical: Fibrocartilaginous mesenchymoma primarily affects young patients, with a median age of 13 years and a slight male predominance. It can present as a painful lesion with localized swelling.
- Micro: Characterized by spindle cells, hyaline cartilage nodules, and bone trabeculae. The spindle cell component is hypocellular to moderately cellular with elongated cells and mildly atypical nuclei.
- Ancillary: Mutations in GNAS, IDH1, and IDH2, as well as amplification of MDM2, were absent in tested tumours. Immunohistochemistry is not helpful.
Reference Gallery:
Fibrocartilaginous mesenchymoma. Enchondral ossification with bone formation at one edge of a cartilagenous nodule.
Fibrocartilaginous mesenchymoma. Anteroposterior radiograph shows an eccentric, lytic lesion in the metadiaphysis and epiphysis of the distal right femur, containing a punctate and hazy internal matrix.
Fibrocartilaginous mesenchymoma. Epiphyseal growth plate–like cartilaginous nodule in a spindle cell proliferation.
Fibrocartilaginous mesenchymoma. Long and short bony trabeculae are present.
Fibrocartilaginous mesenchymoma. Coronal CT shows an eccentric, lytic, expansile lesion in the distal right femoral metadiaphysis with extension into the epiphysis. The lesion contains a punctate and hazy internal matrix and is associated with cortical destruction and a soft tissue mass along the proximal aspect of the lesion medially.
Fibrocartilaginous mesenchymoma. High-power view showing a highly cellular spindle cell component that can resemble fibrosarcoma.

Q: Radiographically, [...] typically presents in young patients as an eccentric, expansile, lytic lesion in the metadiaphysis and epiphysis containing a punctate and hazy internal matrix.
Fibrocartilaginous mesenchymoma. Anteroposterior radiograph shows an eccentric, lytic lesion in the metadiaphysis and epiphysis of the distal right femur, containing a punctate and hazy internal matrix.
Fibrocartilaginous mesenchymoma. Coronal CT shows an eccentric, lytic, expansile lesion in the distal right femoral metadiaphysis with extension into the epiphysis. The lesion contains a punctate and hazy internal matrix and is associated with cortical destruction and a soft tissue mass along the proximal aspect of the lesion medially.
A: Fibrocartilaginous Mesenchymoma
Back Extra: Fibrocartilaginous Mesenchymoma
- Clinical: Fibrocartilaginous mesenchymoma primarily affects young patients, with a median age of 13 years and a slight male predominance. It can present as a painful lesion with localized swelling.
- Micro: Characterized by spindle cells, hyaline cartilage nodules, and bone trabeculae. The spindle cell component is hypocellular to moderately cellular with elongated cells and mildly atypical nuclei.
- Ancillary: Mutations in GNAS, IDH1, and IDH2, as well as amplification of MDM2, were absent in tested tumours. Immunohistochemistry is not helpful.
Reference Gallery:
Fibrocartilaginous mesenchymoma. Enchondral ossification with bone formation at one edge of a cartilagenous nodule.
Fibrocartilaginous mesenchymoma. Anteroposterior radiograph shows an eccentric, lytic lesion in the metadiaphysis and epiphysis of the distal right femur, containing a punctate and hazy internal matrix.
Fibrocartilaginous mesenchymoma. Epiphyseal growth plate–like cartilaginous nodule in a spindle cell proliferation.
Fibrocartilaginous mesenchymoma. Long and short bony trabeculae are present.
Fibrocartilaginous mesenchymoma. Coronal CT shows an eccentric, lytic, expansile lesion in the distal right femoral metadiaphysis with extension into the epiphysis. The lesion contains a punctate and hazy internal matrix and is associated with cortical destruction and a soft tissue mass along the proximal aspect of the lesion medially.
Fibrocartilaginous mesenchymoma. High-power view showing a highly cellular spindle cell component that can resemble fibrosarcoma.

Q: Histologically, Fibrous Dysplasia is characterized by irregular, curvilinear trabeculae of [...] in a background of bland spindle cells, sometimes exhibiting Sharpey-like fibers.
Fibrous dysplasia. Typical deposition of woven bone in a background of bland spindle cell proliferation.
Fibrous dysplasia. Higher power showing Sharpey-like fibres, a typical finding in fibrous dysplasia.
A: woven bone
Back Extra: Fibrous Dysplasia
- Clinical: Fibrous dysplasia can present as monostotic or polyostotic forms, often causing pain and fractures, and is associated with endocrinopathies and skin pigment changes in McCune–Albright syndrome.
- Micro: Characterized by irregular, curvilinear trabeculae of woven bone and bland fibroblastic cells, sometimes with Sharpey-like fibers and cartilaginous components.
- Ancillary: Mutations in GNAS are common in fibrous dysplasia, and can help differentiate it from low-grade central osteosarcoma.
Reference Gallery:
Fibrous dysplasia. Typical deposition of woven bone in a background of bland spindle cell proliferation.
Fibrous dysplasia. Higher power showing Sharpey-like fibres, a typical finding in fibrous dysplasia.
Polyostotic fibrous dysplasia. Polyostotic fibrous dysplasia with localizations in proximal femur, pubic bone extending through inferior ramus to acetabulum, and left iliac bone. The lesions have sclerotic, well-defined, lobulated margins and a geographical pattern of destruction, and they exhibit a combination of osteolysis, ground-glass opacities, and sclerotic septations. Also note the varus deformation (shepherd’s crook) of the right femur, which eventually resulted in a fracture.
Fibrous dysplasia. CT of skull with fibrous dysplasia. In flat bones the process is often expansile.
Fibrous dysplasia. Fibrous dysplasia with gross cartilaginous components.

Q: In the polyostotic form of Fibrous Dysplasia, patients can develop a classic varus deformation of the proximal femur that frequently leads to fractures, known radiographically as a [...] deformity.
Polyostotic fibrous dysplasia. Polyostotic fibrous dysplasia with localizations in proximal femur, pubic bone extending through inferior ramus to acetabulum, and left iliac bone. The lesions have sclerotic, well-defined, lobulated margins and a geographical pattern of destruction, and they exhibit a combination of osteolysis, ground-glass opacities, and sclerotic septations. Also note the varus deformation (shepherd’s crook) of the right femur, which eventually resulted in a fracture.
A: shepherd's crook
Back Extra: Fibrous Dysplasia
- Clinical: Fibrous dysplasia can present as monostotic or polyostotic forms, often causing pain and fractures, and is associated with endocrinopathies and skin pigment changes in McCune–Albright syndrome.
- Micro: Characterized by irregular, curvilinear trabeculae of woven bone and bland fibroblastic cells, sometimes with Sharpey-like fibers and cartilaginous components.
- Ancillary: Mutations in GNAS are common in fibrous dysplasia, and can help differentiate it from low-grade central osteosarcoma.
Reference Gallery:
Fibrous dysplasia. Typical deposition of woven bone in a background of bland spindle cell proliferation.
Fibrous dysplasia. Higher power showing Sharpey-like fibres, a typical finding in fibrous dysplasia.
Polyostotic fibrous dysplasia. Polyostotic fibrous dysplasia with localizations in proximal femur, pubic bone extending through inferior ramus to acetabulum, and left iliac bone. The lesions have sclerotic, well-defined, lobulated margins and a geographical pattern of destruction, and they exhibit a combination of osteolysis, ground-glass opacities, and sclerotic septations. Also note the varus deformation (shepherd’s crook) of the right femur, which eventually resulted in a fracture.
Fibrous dysplasia. CT of skull with fibrous dysplasia. In flat bones the process is often expansile.
Fibrous dysplasia. Fibrous dysplasia with gross cartilaginous components.

Q: Although primarily an osseous and fibroblastic lesion, Fibrous Dysplasia can occasionally exhibit prominent [...] components, which must be distinguished from a primary chondroid tumor.
Fibrous dysplasia. Fibrous dysplasia with gross cartilaginous components.
A: cartilaginous
Back Extra: Fibrous Dysplasia
- Clinical: Fibrous dysplasia can present as monostotic or polyostotic forms, often causing pain and fractures, and is associated with endocrinopathies and skin pigment changes in McCune–Albright syndrome.
- Micro: Characterized by irregular, curvilinear trabeculae of woven bone and bland fibroblastic cells, sometimes with Sharpey-like fibers and cartilaginous components.
- Ancillary: Mutations in GNAS are common in fibrous dysplasia, and can help differentiate it from low-grade central osteosarcoma.
Reference Gallery:
Fibrous dysplasia. Typical deposition of woven bone in a background of bland spindle cell proliferation.
Fibrous dysplasia. Higher power showing Sharpey-like fibres, a typical finding in fibrous dysplasia.
Polyostotic fibrous dysplasia. Polyostotic fibrous dysplasia with localizations in proximal femur, pubic bone extending through inferior ramus to acetabulum, and left iliac bone. The lesions have sclerotic, well-defined, lobulated margins and a geographical pattern of destruction, and they exhibit a combination of osteolysis, ground-glass opacities, and sclerotic septations. Also note the varus deformation (shepherd’s crook) of the right femur, which eventually resulted in a fracture.
Fibrous dysplasia. CT of skull with fibrous dysplasia. In flat bones the process is often expansile.
Fibrous dysplasia. Fibrous dysplasia with gross cartilaginous components.

Q: In the microscopic evaluation of Lipoma and Hibernoma of Bone, the lipoma typically consists of mature white adipocytes with a single large vacuole, whereas the hibernoma is characterized by distinct [...] cells containing multiple small clear vacuoles within an eosinophilic cytoplasm.
Lipoma of bone. Large white adipocyte with crescent-shaped nucleus containing intranuclear inclusion.
Hibernoma of bone. Brown fat cells of hibernoma have multiple small clear vacuoles enmeshed in eosinophilic cytoplasm.
A: brown fat
Back Extra: Lipoma and Hibernoma of Bone
- Clinical: Lipomas are typically asymptomatic or cause aching pain, while hibernomas are usually asymptomatic and detected incidentally.
- Micro: Lipomas are composed of lobules of mature adipocytes with a single large clear cytoplasmic vacuole, while hibernomas contain brown fat cells with multiple small clear vacuoles.
- Ancillary: Immunohistochemistry shows lipomas are positive for S100 and negative for CD68, while hibernomas strongly express the brown fat marker UCP1.
Reference Gallery:
Lipoma of bone. Radiograph shows well-circumscribed oval radiolucency, with calcifications.
Lipoma of bone. Coronal T1-weighted MRI demonstrates the lipoma that has high signal intensity and is longer than appreciated on the plain film.
Lipoma of bone. Lipoma within the medullary cavity is well circumscribed.
Lipoma of bone. Large white adipocyte with crescent-shaped nucleus containing intranuclear inclusion.
Hibernoma of bone. Coronal CT shows well-circumscribed hibernoma that is mineralized.
Hibernoma of bone. Brown fat cells of hibernoma have multiple small clear vacuoles enmeshed in eosinophilic cytoplasm.
Parosteal lipoma. Juxtacortical mass is well circumscribed and bubbly in appearance. It contains linear mineralization that is most prominent at its site of attachment to the bone.
Parosteal lipoma. Axial CT shows bone at base of parosteal lipoma surrounded by oval well-circumscribed mass of fat that is dark with low density. Cortex is intact and there is no continuity between the lesion and the bone marrow of the diaphysis.
Parosteal lipoma. Woven bone with a small amount of cartilage at the base beneath lobules of white adipose tissue.
Parosteal lipoma. Parosteal lipoma of rib composed of a juxtacortical, well-defined mass of yellowish fat.

Q: Within the spectrum of Lipoma and Hibernoma of Bone, a lesion presenting radiographically and grossly as a well-circumscribed, juxtacortical fat mass with an intact underlying bony cortex is diagnosed as a [...].
Parosteal lipoma. Axial CT shows bone at base of parosteal lipoma surrounded by oval well-circumscribed mass of fat that is dark with low density. Cortex is intact and there is no continuity between the lesion and the bone marrow of the diaphysis.
Parosteal lipoma. Parosteal lipoma of rib composed of a juxtacortical, well-defined mass of yellowish fat.
A: parosteal lipoma
Back Extra: Lipoma and Hibernoma of Bone
- Clinical: Lipomas are typically asymptomatic or cause aching pain, while hibernomas are usually asymptomatic and detected incidentally.
- Micro: Lipomas are composed of lobules of mature adipocytes with a single large clear cytoplasmic vacuole, while hibernomas contain brown fat cells with multiple small clear vacuoles.
- Ancillary: Immunohistochemistry shows lipomas are positive for S100 and negative for CD68, while hibernomas strongly express the brown fat marker UCP1.
Reference Gallery:
Lipoma of bone. Radiograph shows well-circumscribed oval radiolucency, with calcifications.
Lipoma of bone. Coronal T1-weighted MRI demonstrates the lipoma that has high signal intensity and is longer than appreciated on the plain film.
Lipoma of bone. Lipoma within the medullary cavity is well circumscribed.
Lipoma of bone. Large white adipocyte with crescent-shaped nucleus containing intranuclear inclusion.
Hibernoma of bone. Coronal CT shows well-circumscribed hibernoma that is mineralized.
Hibernoma of bone. Brown fat cells of hibernoma have multiple small clear vacuoles enmeshed in eosinophilic cytoplasm.
Parosteal lipoma. Juxtacortical mass is well circumscribed and bubbly in appearance. It contains linear mineralization that is most prominent at its site of attachment to the bone.
Parosteal lipoma. Axial CT shows bone at base of parosteal lipoma surrounded by oval well-circumscribed mass of fat that is dark with low density. Cortex is intact and there is no continuity between the lesion and the bone marrow of the diaphysis.
Parosteal lipoma. Woven bone with a small amount of cartilage at the base beneath lobules of white adipose tissue.
Parosteal lipoma. Parosteal lipoma of rib composed of a juxtacortical, well-defined mass of yellowish fat.

Q: Histologically, Osteofibrous Dysplasia is characterized by a bland fibrous stroma containing trabeculae of woven bone with prominent [...].
Osteofibrous dysplasia. Osteofibrous dysplasia composed of trabeculae of woven bone with osteoblastic rimming and fibrous tissue.
Osteofibrous dysplasia. Higher-power view of osteofibrous dysplasia demonstrating the woven bone with osteoblastic rimming, surrounded by spindle-shaped cells.
A: osteoblastic rimming
Back Extra: Osteofibrous Dysplasia
- Clinical: Osteofibrous dysplasia typically presents in children with pain, localized swelling, and bowing deformity of the tibia and/or fibula.
- Micro: Histologically, osteofibrous dysplasia is characterized by trabeculae of woven bone with prominent osteoblastic rimming and a fibrous stroma composed of bland spindle-shaped cells.
- Ancillary: Immunohistochemistry shows occasional positive staining for p63 and S100, and single scattered keratin-positive stromal cells.
Reference Gallery:
Osteofibrous dysplasia. Plain radiograph shows a mixed lytic and sclerotic lesion that is causing endosteal scalloping and cortical expansion of the proximal tibial diaphysis.
Osteofibrous dysplasia. Axial CT shows that the tumour is confined to the cortex of the tibia and surrounded by a rim of bone, without involvement of the medullary cavity or soft tissues.
Osteofibrous dysplasia. Axial T1 MRI demonstrates an expansile intracortical tumour causing cortical thinning, without periosteal reaction. There is no infiltration of the adjacent medullary cavity.
Osteofibrous dysplasia. Osteofibrous dysplasia composed of trabeculae of woven bone with osteoblastic rimming and fibrous tissue.
Osteofibrous dysplasia. Higher-power view of osteofibrous dysplasia demonstrating the woven bone with osteoblastic rimming, surrounded by spindle-shaped cells.
Osteofibrous dysplasia. Osteofibrous dysplasia shows single scattered keratin-positive stromal cells. Clusters of keratin-positive cells (as seen in osteofibrous dysplasia–like adamantinoma) are not seen.

Q: Immunohistochemistry in Osteofibrous Dysplasia characteristically highlights single scattered stromal cells that are positive for [...], distinguishing it from the cellular clusters seen in adamantinoma.
Osteofibrous dysplasia. Osteofibrous dysplasia shows single scattered keratin-positive stromal cells. Clusters of keratin-positive cells (as seen in osteofibrous dysplasia–like adamantinoma) are not seen.
A: keratin
Back Extra: Osteofibrous Dysplasia
- Clinical: Osteofibrous dysplasia typically presents in children with pain, localized swelling, and bowing deformity of the tibia and/or fibula.
- Micro: Histologically, osteofibrous dysplasia is characterized by trabeculae of woven bone with prominent osteoblastic rimming and a fibrous stroma composed of bland spindle-shaped cells.
- Ancillary: Immunohistochemistry shows occasional positive staining for p63 and S100, and single scattered keratin-positive stromal cells.
Reference Gallery:
Osteofibrous dysplasia. Plain radiograph shows a mixed lytic and sclerotic lesion that is causing endosteal scalloping and cortical expansion of the proximal tibial diaphysis.
Osteofibrous dysplasia. Axial CT shows that the tumour is confined to the cortex of the tibia and surrounded by a rim of bone, without involvement of the medullary cavity or soft tissues.
Osteofibrous dysplasia. Axial T1 MRI demonstrates an expansile intracortical tumour causing cortical thinning, without periosteal reaction. There is no infiltration of the adjacent medullary cavity.
Osteofibrous dysplasia. Osteofibrous dysplasia composed of trabeculae of woven bone with osteoblastic rimming and fibrous tissue.
Osteofibrous dysplasia. Higher-power view of osteofibrous dysplasia demonstrating the woven bone with osteoblastic rimming, surrounded by spindle-shaped cells.
Osteofibrous dysplasia. Osteofibrous dysplasia shows single scattered keratin-positive stromal cells. Clusters of keratin-positive cells (as seen in osteofibrous dysplasia–like adamantinoma) are not seen.

Q: Radiographically, Osteofibrous Dysplasia presents in children as a mixed lytic and sclerotic, expansile intracortical lesion almost exclusively located in the diaphysis of the [...] and/or fibula, often causing a bowing deformity.
Osteofibrous dysplasia. Plain radiograph shows a mixed lytic and sclerotic lesion that is causing endosteal scalloping and cortical expansion of the proximal tibial diaphysis.
Osteofibrous dysplasia. Axial CT shows that the tumour is confined to the cortex of the tibia and surrounded by a rim of bone, without involvement of the medullary cavity or soft tissues.
A: tibia
Back Extra: Osteofibrous Dysplasia
- Clinical: Osteofibrous dysplasia typically presents in children with pain, localized swelling, and bowing deformity of the tibia and/or fibula.
- Micro: Histologically, osteofibrous dysplasia is characterized by trabeculae of woven bone with prominent osteoblastic rimming and a fibrous stroma composed of bland spindle-shaped cells.
- Ancillary: Immunohistochemistry shows occasional positive staining for p63 and S100, and single scattered keratin-positive stromal cells.
Reference Gallery:
Osteofibrous dysplasia. Plain radiograph shows a mixed lytic and sclerotic lesion that is causing endosteal scalloping and cortical expansion of the proximal tibial diaphysis.
Osteofibrous dysplasia. Axial CT shows that the tumour is confined to the cortex of the tibia and surrounded by a rim of bone, without involvement of the medullary cavity or soft tissues.
Osteofibrous dysplasia. Axial T1 MRI demonstrates an expansile intracortical tumour causing cortical thinning, without periosteal reaction. There is no infiltration of the adjacent medullary cavity.
Osteofibrous dysplasia. Osteofibrous dysplasia composed of trabeculae of woven bone with osteoblastic rimming and fibrous tissue.
Osteofibrous dysplasia. Higher-power view of osteofibrous dysplasia demonstrating the woven bone with osteoblastic rimming, surrounded by spindle-shaped cells.
Osteofibrous dysplasia. Osteofibrous dysplasia shows single scattered keratin-positive stromal cells. Clusters of keratin-positive cells (as seen in osteofibrous dysplasia–like adamantinoma) are not seen.

Q: On plain radiography, the finding of a fallen leaf sign following a pathologic fracture is highly characteristic of a hollow lesion such as a [...].
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
A: Simple Bone Cyst
Q: Simple Bone Cyst
- Clinical: [...] are often asymptomatic but can present with mild pain, swelling, or limitation of motion, especially after a pathological fracture.
- Micro: The lining of a [...] is composed of a thin layer of fibrous tissue containing fibroblasts, small blood vessels, and may include foci of chronic inflammation, giant cells, and haemosiderin.
- Ancillary: MRI is useful in diagnosing [...], showing low signal intensity on T1-weighted images and bright, homogeneous signal intensity on T2-weighted images.
Reference Gallery:
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. Simple bone cysts may occur in the calcaneus in older patients.
Simple bone cyst. MRI highlighting the increased signal intensity of the cyst contents on T2-weighted images.
Simple bone cyst. T1 MRI highlights the circumscribed borders of the cyst and the low signal intensity of its contents.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
Simple bone cyst. Foci of foamy histiocytes are commonly found in the cyst wall.
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
A: Simple bone cysts; simple bone cyst; simple bone cysts

Q: On MRI, a Simple Bone Cyst typically exhibits low signal intensity on T1-weighted images and bright, homogeneous signal intensity on [...] images due to its fluid contents.
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. T1 MRI highlights the circumscribed borders of the cyst and the low signal intensity of its contents.
A: T2-weighted
Q: Simple Bone Cyst
- Clinical: [...] are often asymptomatic but can present with mild pain, swelling, or limitation of motion, especially after a pathological fracture.
- Micro: The lining of a [...] is composed of a thin layer of fibrous tissue containing fibroblasts, small blood vessels, and may include foci of chronic inflammation, giant cells, and haemosiderin.
- Ancillary: MRI is useful in diagnosing [...], showing low signal intensity on T1-weighted images and bright, homogeneous signal intensity on T2-weighted images.
Reference Gallery:
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. Simple bone cysts may occur in the calcaneus in older patients.
Simple bone cyst. MRI highlighting the increased signal intensity of the cyst contents on T2-weighted images.
Simple bone cyst. T1 MRI highlights the circumscribed borders of the cyst and the low signal intensity of its contents.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
Simple bone cyst. Foci of foamy histiocytes are commonly found in the cyst wall.
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
A: Simple bone cysts; simple bone cyst; simple bone cysts

Q: Histologically, the wall of a Simple Bone Cyst consists of a thin layer of fibrous tissue that commonly contains characteristic [...], which may subsequently calcify or ossify.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
A: fibrin-like deposits
Q: Simple Bone Cyst
- Clinical: [...] are often asymptomatic but can present with mild pain, swelling, or limitation of motion, especially after a pathological fracture.
- Micro: The lining of a [...] is composed of a thin layer of fibrous tissue containing fibroblasts, small blood vessels, and may include foci of chronic inflammation, giant cells, and haemosiderin.
- Ancillary: MRI is useful in diagnosing [...], showing low signal intensity on T1-weighted images and bright, homogeneous signal intensity on T2-weighted images.
Reference Gallery:
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. Simple bone cysts may occur in the calcaneus in older patients.
Simple bone cyst. MRI highlighting the increased signal intensity of the cyst contents on T2-weighted images.
Simple bone cyst. T1 MRI highlights the circumscribed borders of the cyst and the low signal intensity of its contents.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
Simple bone cyst. Foci of foamy histiocytes are commonly found in the cyst wall.
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
A: Simple bone cysts; simple bone cyst; simple bone cysts

Q: Microscopically, classic Adamantinoma of long bones is characterized by a biphasic appearance featuring prominent [...] components (which may form tubular, basaloid, spindle, or squamous patterns) surrounded by a fibrous stroma.
Classic adamantinoma. Biopsy from the tibial lesion shows classic adamantinoma with the neoplastic epithelial cells forming tubular structures.
Classic adamantinoma. Basaloid pattern with the peripheral palisading of the tumour cells surrounding inner spindle-shaped cells.
Classic adamantinoma. Squamous differentiation, where the centre of the epithelial islands shows obvious keratinization, is the rarest subtype of adamantinoma.
A: epithelial
Back Extra: Adamantinoma of long bones
- Clinical: Adamantinoma of long bones typically presents as a painful or painless swelling with a protracted clinical course, often lasting over 30 years before diagnosis.
- Micro: The microscopic appearance of classic adamantinoma includes prominent epithelial components forming tubular, spindle, basaloid, or squamous patterns, while the osteofibrous dysplasia–like variant has small nests of epithelial cells within a fibrous stroma.
- Ancillary: Immunohistochemistry in adamantinoma shows coexpression of keratin, EMA, vimentin, p63, and podoplanin, with a predominant basal epithelial cell differentiation.
Reference Gallery:
Classic adamantinoma. Biopsy from the tibial lesion shows classic adamantinoma with the neoplastic epithelial cells forming tubular structures.
Osteofibrous dysplasia–like adamantinoma. Osteofibrous dysplasia–like adamantinomatous areas that look like osteofibrous dysplasia with trabeculae of woven bone rimmed by plump osteoblasts. Within the fibrous stroma there are small nests of epithelial cells (inside circle) that are hard to see on H&E-stained slides and may mimic endothelial cells.
Classic adamantinoma. Basaloid pattern with the peripheral palisading of the tumour cells surrounding inner spindle-shaped cells.
Classic adamantinoma. Squamous differentiation, where the centre of the epithelial islands shows obvious keratinization, is the rarest subtype of adamantinoma.
Classic adamantinoma. A resection specimen from the tibia shows a tan mass involving the medullary cavity associated with a pathological fracture. Proximal to the main tumour there are smaller nodules of tumour associated with sclerosis.
Classic adamantinoma. Classic adamantinoma demonstrating a large expansile osteolytic lesion with soap bubble appearance involving the distal tibia and causing cortical thinning.
Osteofibrous dysplasia–like adamantinoma. In the anterior cortex of the mid-tibial shaft there is an intracortical, multiloculated lytic lesion with surrounding sclerosis.
Osteofibrous dysplasia–like adamantinoma. Axial CT demonstrating lytic lesions with surrounding sclerosis involving the anterior cortex.
Dedifferentiated adamantinoma. Sarcomatous progression of the epithelial component is characteristic of dedifferentiated adamantinoma.
Classic adamantinoma. Spindle cell subtype of adamantinoma with tumour cells arranged in intersecting fascicles. This subtype must be distinguished from intraosseous synovial sarcoma.

Q: The osteofibrous dysplasia–like variant of Adamantinoma of long bones demonstrates small, difficult-to-see nests of epithelial cells within a fibrous stroma containing trabeculae of [...] rimmed by plump osteoblasts.
Osteofibrous dysplasia–like adamantinoma. Osteofibrous dysplasia–like adamantinomatous areas that look like osteofibrous dysplasia with trabeculae of woven bone rimmed by plump osteoblasts. Within the fibrous stroma there are small nests of epithelial cells (inside circle) that are hard to see on H&E-stained slides and may mimic endothelial cells.
A: woven bone
Back Extra: Adamantinoma of long bones
- Clinical: Adamantinoma of long bones typically presents as a painful or painless swelling with a protracted clinical course, often lasting over 30 years before diagnosis.
- Micro: The microscopic appearance of classic adamantinoma includes prominent epithelial components forming tubular, spindle, basaloid, or squamous patterns, while the osteofibrous dysplasia–like variant has small nests of epithelial cells within a fibrous stroma.
- Ancillary: Immunohistochemistry in adamantinoma shows coexpression of keratin, EMA, vimentin, p63, and podoplanin, with a predominant basal epithelial cell differentiation.
Reference Gallery:
Classic adamantinoma. Biopsy from the tibial lesion shows classic adamantinoma with the neoplastic epithelial cells forming tubular structures.
Osteofibrous dysplasia–like adamantinoma. Osteofibrous dysplasia–like adamantinomatous areas that look like osteofibrous dysplasia with trabeculae of woven bone rimmed by plump osteoblasts. Within the fibrous stroma there are small nests of epithelial cells (inside circle) that are hard to see on H&E-stained slides and may mimic endothelial cells.
Classic adamantinoma. Basaloid pattern with the peripheral palisading of the tumour cells surrounding inner spindle-shaped cells.
Classic adamantinoma. Squamous differentiation, where the centre of the epithelial islands shows obvious keratinization, is the rarest subtype of adamantinoma.
Classic adamantinoma. A resection specimen from the tibia shows a tan mass involving the medullary cavity associated with a pathological fracture. Proximal to the main tumour there are smaller nodules of tumour associated with sclerosis.
Classic adamantinoma. Classic adamantinoma demonstrating a large expansile osteolytic lesion with soap bubble appearance involving the distal tibia and causing cortical thinning.
Osteofibrous dysplasia–like adamantinoma. In the anterior cortex of the mid-tibial shaft there is an intracortical, multiloculated lytic lesion with surrounding sclerosis.
Osteofibrous dysplasia–like adamantinoma. Axial CT demonstrating lytic lesions with surrounding sclerosis involving the anterior cortex.
Dedifferentiated adamantinoma. Sarcomatous progression of the epithelial component is characteristic of dedifferentiated adamantinoma.
Classic adamantinoma. Spindle cell subtype of adamantinoma with tumour cells arranged in intersecting fascicles. This subtype must be distinguished from intraosseous synovial sarcoma.

Q: Radiographically, classic Adamantinoma of long bones typically presents in the tibia as a large, expansile, osteolytic lesion with a characteristic [...] appearance and associated cortical thinning.
Classic adamantinoma. Classic adamantinoma demonstrating a large expansile osteolytic lesion with soap bubble appearance involving the distal tibia and causing cortical thinning.
A: soap bubble
Back Extra: Adamantinoma of long bones
- Clinical: Adamantinoma of long bones typically presents as a painful or painless swelling with a protracted clinical course, often lasting over 30 years before diagnosis.
- Micro: The microscopic appearance of classic adamantinoma includes prominent epithelial components forming tubular, spindle, basaloid, or squamous patterns, while the osteofibrous dysplasia–like variant has small nests of epithelial cells within a fibrous stroma.
- Ancillary: Immunohistochemistry in adamantinoma shows coexpression of keratin, EMA, vimentin, p63, and podoplanin, with a predominant basal epithelial cell differentiation.
Reference Gallery:
Classic adamantinoma. Biopsy from the tibial lesion shows classic adamantinoma with the neoplastic epithelial cells forming tubular structures.
Osteofibrous dysplasia–like adamantinoma. Osteofibrous dysplasia–like adamantinomatous areas that look like osteofibrous dysplasia with trabeculae of woven bone rimmed by plump osteoblasts. Within the fibrous stroma there are small nests of epithelial cells (inside circle) that are hard to see on H&E-stained slides and may mimic endothelial cells.
Classic adamantinoma. Basaloid pattern with the peripheral palisading of the tumour cells surrounding inner spindle-shaped cells.
Classic adamantinoma. Squamous differentiation, where the centre of the epithelial islands shows obvious keratinization, is the rarest subtype of adamantinoma.
Classic adamantinoma. A resection specimen from the tibia shows a tan mass involving the medullary cavity associated with a pathological fracture. Proximal to the main tumour there are smaller nodules of tumour associated with sclerosis.
Classic adamantinoma. Classic adamantinoma demonstrating a large expansile osteolytic lesion with soap bubble appearance involving the distal tibia and causing cortical thinning.
Osteofibrous dysplasia–like adamantinoma. In the anterior cortex of the mid-tibial shaft there is an intracortical, multiloculated lytic lesion with surrounding sclerosis.
Osteofibrous dysplasia–like adamantinoma. Axial CT demonstrating lytic lesions with surrounding sclerosis involving the anterior cortex.
Dedifferentiated adamantinoma. Sarcomatous progression of the epithelial component is characteristic of dedifferentiated adamantinoma.
Classic adamantinoma. Spindle cell subtype of adamantinoma with tumour cells arranged in intersecting fascicles. This subtype must be distinguished from intraosseous synovial sarcoma.

Q: The defining genetic feature of Ewing sarcoma is a t(11;22) translocation, which results in the [...] fusion transcript.
The EWSR1-FLI1 fusion. The most common Ewing sarcoma translocation is between the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. The EWSR1 protein has an N-terminal domain (NTD) that is an intrinsically disordered domain and a C-terminal region that contains RGG domains and an RNA-recognition motif (RRM). The FLI1 protein has an N-terminal domain with a pointed protein–protein interaction domain (PNT) and an ETS-type DNA-binding domain (DNABD) in its C-terminus. The resulting EWSR1-FLI1 protein retains the EWSR1 NTD and the FLI1 DNABD.
Next-generation sequencing of EWSR1-FLI1. Next-generation RNA sequencing of Ewing sarcoma demonstrates in-frame fusion between EWSR1 and FLI1 gene products. Next-generation sequencing is more specific than EWSR1 break-apart FISH because it provides detailed information about both translocation partners.
A: EWSR1-FLI1
Back Extra: Ewing Sarcoma
- Clinical: Ewing sarcoma often presents with locoregional pain, a palpable mass, and sometimes pathological fracture or fever.
- Micro: Classic Ewing sarcoma is characterized by uniform small round cells with finely stippled chromatin and indistinct cytoplasmic membranes.
- Ancillary: The most common genetic translocation in Ewing sarcoma is t(11;22)(q24;q12), resulting in the EWSR1-FLI1 fusion transcript.
Reference Gallery:
The EWSR1-FLI1 fusion. The most common Ewing sarcoma translocation is between the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. The EWSR1 protein has an N-terminal domain (NTD) that is an intrinsically disordered domain and a C-terminal region that contains RGG domains and an RNA-recognition motif (RRM). The FLI1 protein has an N-terminal domain with a pointed protein–protein interaction domain (PNT) and an ETS-type DNA-binding domain (DNABD) in its C-terminus. The resulting EWSR1-FLI1 protein retains the EWSR1 NTD and the FLI1 DNABD.
Next-generation sequencing of EWSR1-FLI1. Next-generation RNA sequencing of Ewing sarcoma demonstrates in-frame fusion between EWSR1 and FLI1 gene products. Next-generation sequencing is more specific than EWSR1 break-apart FISH because it provides detailed information about both translocation partners.
Classic Ewing sarcoma. Notice the vaguely lobular pattern and cleared-out cytoplasm, due to glycogen deposits.
Ewing sarcoma. A classic Ewing sarcoma (A) can be compared with atypical Ewing sarcoma (B) in terms of nuclear size, chromatin structure, and cytoplasmic clearing.
Ewing sarcoma. Ewing sarcoma with extensive neuroectodermal differentiation (formerly called primitive neuroectodermal tumour) showing well-formed pseudorosettes, absence of nucleoli, and finely granular chromatin.
Ewing sarcoma. Ewing sarcoma typically shows strong and diffuse membrane staining for CD99.
Bone Ewing sarcoma. Anteroposterior radiograph of the right humerus shows an aggressive lesion in the proximal metadiaphysis, with permeative bone destruction, cortical lysis, and a multilamellated periosteal reaction, which is interrupted medially and laterally.

Q: Immunohistochemistry for Ewing sarcoma characteristically exhibits strong, diffuse membranous positivity for [...].
Ewing sarcoma. Ewing sarcoma typically shows strong and diffuse membrane staining for CD99.
A: CD99
Back Extra: Ewing Sarcoma
- Clinical: Ewing sarcoma often presents with locoregional pain, a palpable mass, and sometimes pathological fracture or fever.
- Micro: Classic Ewing sarcoma is characterized by uniform small round cells with finely stippled chromatin and indistinct cytoplasmic membranes.
- Ancillary: The most common genetic translocation in Ewing sarcoma is t(11;22)(q24;q12), resulting in the EWSR1-FLI1 fusion transcript.
Reference Gallery:
The EWSR1-FLI1 fusion. The most common Ewing sarcoma translocation is between the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. The EWSR1 protein has an N-terminal domain (NTD) that is an intrinsically disordered domain and a C-terminal region that contains RGG domains and an RNA-recognition motif (RRM). The FLI1 protein has an N-terminal domain with a pointed protein–protein interaction domain (PNT) and an ETS-type DNA-binding domain (DNABD) in its C-terminus. The resulting EWSR1-FLI1 protein retains the EWSR1 NTD and the FLI1 DNABD.
Next-generation sequencing of EWSR1-FLI1. Next-generation RNA sequencing of Ewing sarcoma demonstrates in-frame fusion between EWSR1 and FLI1 gene products. Next-generation sequencing is more specific than EWSR1 break-apart FISH because it provides detailed information about both translocation partners.
Classic Ewing sarcoma. Notice the vaguely lobular pattern and cleared-out cytoplasm, due to glycogen deposits.
Ewing sarcoma. A classic Ewing sarcoma (A) can be compared with atypical Ewing sarcoma (B) in terms of nuclear size, chromatin structure, and cytoplasmic clearing.
Ewing sarcoma. Ewing sarcoma with extensive neuroectodermal differentiation (formerly called primitive neuroectodermal tumour) showing well-formed pseudorosettes, absence of nucleoli, and finely granular chromatin.
Ewing sarcoma. Ewing sarcoma typically shows strong and diffuse membrane staining for CD99.
Bone Ewing sarcoma. Anteroposterior radiograph of the right humerus shows an aggressive lesion in the proximal metadiaphysis, with permeative bone destruction, cortical lysis, and a multilamellated periosteal reaction, which is interrupted medially and laterally.

Q: On plain radiographs, a bone Ewing sarcoma often displays permeative destruction accompanied by a characteristic [...] (or "onion-skin") periosteal reaction.
Bone Ewing sarcoma. Anteroposterior radiograph of the right humerus shows an aggressive lesion in the proximal metadiaphysis, with permeative bone destruction, cortical lysis, and a multilamellated periosteal reaction, which is interrupted medially and laterally.
A: multilamellated
Back Extra: Ewing Sarcoma
- Clinical: Ewing sarcoma often presents with locoregional pain, a palpable mass, and sometimes pathological fracture or fever.
- Micro: Classic Ewing sarcoma is characterized by uniform small round cells with finely stippled chromatin and indistinct cytoplasmic membranes.
- Ancillary: The most common genetic translocation in Ewing sarcoma is t(11;22)(q24;q12), resulting in the EWSR1-FLI1 fusion transcript.
Reference Gallery:
The EWSR1-FLI1 fusion. The most common Ewing sarcoma translocation is between the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. The EWSR1 protein has an N-terminal domain (NTD) that is an intrinsically disordered domain and a C-terminal region that contains RGG domains and an RNA-recognition motif (RRM). The FLI1 protein has an N-terminal domain with a pointed protein–protein interaction domain (PNT) and an ETS-type DNA-binding domain (DNABD) in its C-terminus. The resulting EWSR1-FLI1 protein retains the EWSR1 NTD and the FLI1 DNABD.
Next-generation sequencing of EWSR1-FLI1. Next-generation RNA sequencing of Ewing sarcoma demonstrates in-frame fusion between EWSR1 and FLI1 gene products. Next-generation sequencing is more specific than EWSR1 break-apart FISH because it provides detailed information about both translocation partners.
Classic Ewing sarcoma. Notice the vaguely lobular pattern and cleared-out cytoplasm, due to glycogen deposits.
Ewing sarcoma. A classic Ewing sarcoma (A) can be compared with atypical Ewing sarcoma (B) in terms of nuclear size, chromatin structure, and cytoplasmic clearing.
Ewing sarcoma. Ewing sarcoma with extensive neuroectodermal differentiation (formerly called primitive neuroectodermal tumour) showing well-formed pseudorosettes, absence of nucleoli, and finely granular chromatin.
Ewing sarcoma. Ewing sarcoma typically shows strong and diffuse membrane staining for CD99.
Bone Ewing sarcoma. Anteroposterior radiograph of the right humerus shows an aggressive lesion in the proximal metadiaphysis, with permeative bone destruction, cortical lysis, and a multilamellated periosteal reaction, which is interrupted medially and laterally.

Q: Radiographically, Leiomyosarcoma of Bone typically presents as an aggressive, permeative [...] lesion, often accompanied by cortical destruction.
Leiomyosarcoma. X-ray of a tumour in the distal femur showing an aggressive, permeative lytic lesion with cortical destruction.
A: lytic
Back Extra: Leiomyosarcoma of Bone
- Clinical: Patients with Leiomyosarcoma of Bone typically present with pain and may have a pathological fracture. Imaging shows lytic, aggressive lesions with cortical destruction.
- Micro: Leiomyosarcoma of Bone shows a tan, fleshy, creamy appearance on cut sections, with areas of necrosis. Histopathology reveals spindle cells in long, intersecting fascicles with fibrillary, eosinophilic cytoplasm and elongated nuclei.
- Ancillary: Immunohistochemistry demonstrates smooth muscle differentiation with diffuse staining for desmin and SMA. Genomic losses and absence of phosphorylated RB1 are common findings.
Reference Gallery:
Leiomyosarcoma. X-ray of a tumour in the distal femur showing an aggressive, permeative lytic lesion with cortical destruction.
Leiomyosarcoma. Femoral macroscopy. Note both an intraosseous and an extraosseous component of the white fleshy tumour.
Leiomyosarcoma. Low-power image showing bundles of spindle cells.
Leiomyosarcoma. On high power, cellular pleomorphism of the tumour cells is seen.

Q: On macroscopy, Leiomyosarcoma of Bone frequently appears as a white, [...] tumor that may exhibit both intraosseous and extraosseous components.
Leiomyosarcoma. Femoral macroscopy. Note both an intraosseous and an extraosseous component of the white fleshy tumour.
A: fleshy
Back Extra: Leiomyosarcoma of Bone
- Clinical: Patients with Leiomyosarcoma of Bone typically present with pain and may have a pathological fracture. Imaging shows lytic, aggressive lesions with cortical destruction.
- Micro: Leiomyosarcoma of Bone shows a tan, fleshy, creamy appearance on cut sections, with areas of necrosis. Histopathology reveals spindle cells in long, intersecting fascicles with fibrillary, eosinophilic cytoplasm and elongated nuclei.
- Ancillary: Immunohistochemistry demonstrates smooth muscle differentiation with diffuse staining for desmin and SMA. Genomic losses and absence of phosphorylated RB1 are common findings.
Reference Gallery:
Leiomyosarcoma. X-ray of a tumour in the distal femur showing an aggressive, permeative lytic lesion with cortical destruction.
Leiomyosarcoma. Femoral macroscopy. Note both an intraosseous and an extraosseous component of the white fleshy tumour.
Leiomyosarcoma. Low-power image showing bundles of spindle cells.
Leiomyosarcoma. On high power, cellular pleomorphism of the tumour cells is seen.

Q: The histopathology of Leiomyosarcoma of Bone is characterized by bundles or long, intersecting fascicles of pleomorphic [...] with fibrillary, eosinophilic cytoplasm.
Leiomyosarcoma. Low-power image showing bundles of spindle cells.
Leiomyosarcoma. On high power, cellular pleomorphism of the tumour cells is seen.
A: spindle cells
Back Extra: Leiomyosarcoma of Bone
- Clinical: Patients with Leiomyosarcoma of Bone typically present with pain and may have a pathological fracture. Imaging shows lytic, aggressive lesions with cortical destruction.
- Micro: Leiomyosarcoma of Bone shows a tan, fleshy, creamy appearance on cut sections, with areas of necrosis. Histopathology reveals spindle cells in long, intersecting fascicles with fibrillary, eosinophilic cytoplasm and elongated nuclei.
- Ancillary: Immunohistochemistry demonstrates smooth muscle differentiation with diffuse staining for desmin and SMA. Genomic losses and absence of phosphorylated RB1 are common findings.
Reference Gallery:
Leiomyosarcoma. X-ray of a tumour in the distal femur showing an aggressive, permeative lytic lesion with cortical destruction.
Leiomyosarcoma. Femoral macroscopy. Note both an intraosseous and an extraosseous component of the white fleshy tumour.
Leiomyosarcoma. Low-power image showing bundles of spindle cells.
Leiomyosarcoma. On high power, cellular pleomorphism of the tumour cells is seen.

Q: Elderly patients presenting with severe bone pain, multiple destructive skeletal lesions (e.g., in the pelvis or spine), and pathological fractures are highly suspected to have [...].
Metastatic carcinoma in pelvic bone. Multiple skeletal lesions in elderly patients are suggestive of metastatic spread.
Metastatic carcinoma in the spine. Gross photography showing a solid vertebral lesion involving multiple levels.
A: Bone Metastases
Back Extra: Bone Metastases
- Clinical: Pain is usually the first symptom of {{Bone Metastases}}, and pathological fractures are common.
- Micro: Metastases often present with features similar to the primary lesion, such as adenocarcinomas or squamous cell carcinomas.
- Ancillary: Immunohistochemistry is crucial to suggest or confirm the primary origin of {{Bone Metastases}}.
Reference Gallery:
Metastatic carcinoma in pelvic bone. Multiple skeletal lesions in elderly patients are suggestive of metastatic spread.
Metastasis from renal carcinoma. Radiography of hip with large solitary skeletal lesion.
Metastatic carcinoma in the spine. Gross photography showing a solid vertebral lesion involving multiple levels.
Metastasis from breast carcinoma. Medium-power microscopic view showing small infiltrating glands. Comparison with the specimen from the original cancer site is often necessary.
Metastasis from breast carcinoma. Staining for ER is positive.

Q: Histologic evaluation of [...] typically reveals morphology resembling the primary tumor, and establishing the exact origin relies heavily on ancillary immunohistochemistry (e.g., ER positivity for a breast primary).
Metastasis from breast carcinoma. Medium-power microscopic view showing small infiltrating glands. Comparison with the specimen from the original cancer site is often necessary.
Metastasis from breast carcinoma. Staining for ER is positive.
A: Bone Metastases
Back Extra: Bone Metastases
- Clinical: Pain is usually the first symptom of {{Bone Metastases}}, and pathological fractures are common.
- Micro: Metastases often present with features similar to the primary lesion, such as adenocarcinomas or squamous cell carcinomas.
- Ancillary: Immunohistochemistry is crucial to suggest or confirm the primary origin of {{Bone Metastases}}.
Reference Gallery:
Metastatic carcinoma in pelvic bone. Multiple skeletal lesions in elderly patients are suggestive of metastatic spread.
Metastasis from renal carcinoma. Radiography of hip with large solitary skeletal lesion.
Metastatic carcinoma in the spine. Gross photography showing a solid vertebral lesion involving multiple levels.
Metastasis from breast carcinoma. Medium-power microscopic view showing small infiltrating glands. Comparison with the specimen from the original cancer site is often necessary.
Metastasis from breast carcinoma. Staining for ER is positive.

Q: In Round Cell Sarcoma with EWSR1-non-ETS Fusions, particularly the NFATC2 subtypes, tumor cells are characteristically arranged in cords, nests, or pseudoacinar structures within a [...] stromal background.
EWSR1-NFATC2 sarcoma. Tumour cells embedded in fibrohyaline stroma.
A: fibrohyaline or myxohyaline
Back Extra: Round Cell Sarcoma with EWSR1-non-ETS Fusions
- Clinical: Round Cell Sarcoma with EWSR1-non-ETS Fusions presents as frequently painful, locally destructive bone lesions that may invade surrounding soft tissue or as well-circumscribed primary soft tissue tumours.
- Micro: EWSR1-NFATC2 and FUS-NFATC2 sarcomas are composed of small to medium-sized round and/or spindled cells with limited eosinophilic or clear cytoplasm, arranged in cords, small nests, trabeculae, and pseudoacinar structures in a fibrohyaline or myxohyaline stromal background.
- Ancillary: Identification of EWSR1-NFATC2, FUS-NFATC2, and EWSR1-PATZ1 fusions can be achieved using molecular approaches, though EWSR1 break-apart probes may have limited sensitivity for detecting the EWSR1-PATZ1 fusion.
Reference Gallery:
EWSR1-NFATC2 sarcoma. Multicolour FISH of an EWSR1-NFATC2 fusion–positive case exhibiting a ring chromosome derived from multiple alternating segments of chromosomes 20 and 22 (arrow).
EWSR1-NFATC2 sarcoma. Sarcomas with NFATC2 rearrangement infiltrating and destroying bone.
EWSR1-NFATC2 sarcoma. The tumour is composed of an undifferentiated round cell proliferation without admixed stroma and cytological features reminiscent of Ewing sarcoma.
EWSR1-NFATC2 sarcoma. Diffuse expression of CD99.
EWSR1-NFATC2 sarcoma. Tumour cells embedded in fibrohyaline stroma.
EWSR1-PATZ1 sarcoma. Small to medium-sized tumour nuclei are round to ovoid, with fine granular chromatin.
EWSR1-PATZ1 sarcoma. Tumour nuclei may exhibit mild atypia with size/shape variation and coarse chromatin.
EWSR1-NFATC2 sarcoma. EWSR1 break-apart FISH demonstrates split signals with amplification of the telomeric probe (green); normal cells with colocalized signals are seen on the left.
EWSR1-PATZ1 fusion sarcoma. A Detection of the EWSR1-PATZ1 fusion by RT-PCR. B Direct sequencing demonstrates the nucleotide sequence and deduced amino acid sequence around the EWSR1-PATZ1 fusion point. C Schematic representation of the EWSR1 and PATZ1 genomic organization and fusion transcript.

Q: Although genetically distinct, undifferentiated areas of Round Cell Sarcoma with EWSR1-non-ETS Fusions (such as EWSR1-NFATC2 tumors) can mimic Ewing sarcoma cytologically and show diffuse immunohistochemical expression of [...].
EWSR1-NFATC2 sarcoma. The tumour is composed of an undifferentiated round cell proliferation without admixed stroma and cytological features reminiscent of Ewing sarcoma.
EWSR1-NFATC2 sarcoma. Diffuse expression of CD99.
A: CD99
Back Extra: Round Cell Sarcoma with EWSR1-non-ETS Fusions
- Clinical: Round Cell Sarcoma with EWSR1-non-ETS Fusions presents as frequently painful, locally destructive bone lesions that may invade surrounding soft tissue or as well-circumscribed primary soft tissue tumours.
- Micro: EWSR1-NFATC2 and FUS-NFATC2 sarcomas are composed of small to medium-sized round and/or spindled cells with limited eosinophilic or clear cytoplasm, arranged in cords, small nests, trabeculae, and pseudoacinar structures in a fibrohyaline or myxohyaline stromal background.
- Ancillary: Identification of EWSR1-NFATC2, FUS-NFATC2, and EWSR1-PATZ1 fusions can be achieved using molecular approaches, though EWSR1 break-apart probes may have limited sensitivity for detecting the EWSR1-PATZ1 fusion.
Reference Gallery:
EWSR1-NFATC2 sarcoma. Multicolour FISH of an EWSR1-NFATC2 fusion–positive case exhibiting a ring chromosome derived from multiple alternating segments of chromosomes 20 and 22 (arrow).
EWSR1-NFATC2 sarcoma. Sarcomas with NFATC2 rearrangement infiltrating and destroying bone.
EWSR1-NFATC2 sarcoma. The tumour is composed of an undifferentiated round cell proliferation without admixed stroma and cytological features reminiscent of Ewing sarcoma.
EWSR1-NFATC2 sarcoma. Diffuse expression of CD99.
EWSR1-NFATC2 sarcoma. Tumour cells embedded in fibrohyaline stroma.
EWSR1-PATZ1 sarcoma. Small to medium-sized tumour nuclei are round to ovoid, with fine granular chromatin.
EWSR1-PATZ1 sarcoma. Tumour nuclei may exhibit mild atypia with size/shape variation and coarse chromatin.
EWSR1-NFATC2 sarcoma. EWSR1 break-apart FISH demonstrates split signals with amplification of the telomeric probe (green); normal cells with colocalized signals are seen on the left.
EWSR1-PATZ1 fusion sarcoma. A Detection of the EWSR1-PATZ1 fusion by RT-PCR. B Direct sequencing demonstrates the nucleotide sequence and deduced amino acid sequence around the EWSR1-PATZ1 fusion point. C Schematic representation of the EWSR1 and PATZ1 genomic organization and fusion transcript.

Q: The definitive diagnosis of Round Cell Sarcoma with EWSR1-non-ETS Fusions requires molecular confirmation; importantly, standard EWSR1 break-apart FISH may have limited sensitivity for detecting the [...] fusion variant.
EWSR1-PATZ1 sarcoma. Tumour nuclei may exhibit mild atypia with size/shape variation and coarse chromatin.
EWSR1-PATZ1 fusion sarcoma. A Detection of the EWSR1-PATZ1 fusion by RT-PCR. B Direct sequencing demonstrates the nucleotide sequence and deduced amino acid sequence around the EWSR1-PATZ1 fusion point. C Schematic representation of the EWSR1 and PATZ1 genomic organization and fusion transcript.
A: EWSR1-PATZ1
Back Extra: Round Cell Sarcoma with EWSR1-non-ETS Fusions
- Clinical: Round Cell Sarcoma with EWSR1-non-ETS Fusions presents as frequently painful, locally destructive bone lesions that may invade surrounding soft tissue or as well-circumscribed primary soft tissue tumours.
- Micro: EWSR1-NFATC2 and FUS-NFATC2 sarcomas are composed of small to medium-sized round and/or spindled cells with limited eosinophilic or clear cytoplasm, arranged in cords, small nests, trabeculae, and pseudoacinar structures in a fibrohyaline or myxohyaline stromal background.
- Ancillary: Identification of EWSR1-NFATC2, FUS-NFATC2, and EWSR1-PATZ1 fusions can be achieved using molecular approaches, though EWSR1 break-apart probes may have limited sensitivity for detecting the EWSR1-PATZ1 fusion.
Reference Gallery:
EWSR1-NFATC2 sarcoma. Multicolour FISH of an EWSR1-NFATC2 fusion–positive case exhibiting a ring chromosome derived from multiple alternating segments of chromosomes 20 and 22 (arrow).
EWSR1-NFATC2 sarcoma. Sarcomas with NFATC2 rearrangement infiltrating and destroying bone.
EWSR1-NFATC2 sarcoma. The tumour is composed of an undifferentiated round cell proliferation without admixed stroma and cytological features reminiscent of Ewing sarcoma.
EWSR1-NFATC2 sarcoma. Diffuse expression of CD99.
EWSR1-NFATC2 sarcoma. Tumour cells embedded in fibrohyaline stroma.
EWSR1-PATZ1 sarcoma. Small to medium-sized tumour nuclei are round to ovoid, with fine granular chromatin.
EWSR1-PATZ1 sarcoma. Tumour nuclei may exhibit mild atypia with size/shape variation and coarse chromatin.
EWSR1-NFATC2 sarcoma. EWSR1 break-apart FISH demonstrates split signals with amplification of the telomeric probe (green); normal cells with colocalized signals are seen on the left.
EWSR1-PATZ1 fusion sarcoma. A Detection of the EWSR1-PATZ1 fusion by RT-PCR. B Direct sequencing demonstrates the nucleotide sequence and deduced amino acid sequence around the EWSR1-PATZ1 fusion point. C Schematic representation of the EWSR1 and PATZ1 genomic organization and fusion transcript.

Q: Histologically characterized by marked cytological pleomorphism, multinucleated giant tumor cells, and numerous atypical mitoses, [...] is a diagnosis of exclusion that lacks an identifiable line of differentiation on immunohistochemistry.
Undifferentiated pleomorphic sarcoma. Marked cytological pleomorphism characterized by giant tumour cells with large hyperchromatic nuclei and atypical mitoses.
Undifferentiated pleomorphic sarcoma of bone. Marked cytological pleomorphism characterized by giant tumour cells with large hyperchromatic nuclei.
A: Undifferentiated Pleomorphic Sarcoma of Bone
Back Extra: Undifferentiated Pleomorphic Sarcoma of Bone
- Clinical: Undifferentiated Pleomorphic Sarcoma of Bone typically presents with pain and swelling, and is often associated with pathological fractures in weight-bearing long bones.
- Micro: The tumour is characterized by marked pleomorphism with spindle-shaped and epithelioid cells, multinucleated giant cells, and numerous atypical mitotic figures.
- Ancillary: Immunohistochemistry is crucial for diagnosis, as UPS lacks an identifiable line of differentiation and is a diagnosis of exclusion.
Reference Gallery:
Undifferentiated pleomorphic sarcoma. Marked cytological pleomorphism characterized by giant tumour cells with large hyperchromatic nuclei and atypical mitoses.
Undifferentiated pleomorphic sarcoma of bone. Lateral radiograph shows a predominantly osteolytic lesion in the distal femoral diaphysis, with malignant periosteal new bone formation.
Undifferentiated pleomorphic sarcoma of bone. Sagittal T2-weighted fat-suppressed MRI shows a predominantly osteolytic lesion in the distal femoral diaphysis, with malignant periosteal new bone formation and soft tissue mass anteriorly.
Undifferentiated pleomorphic sarcoma of bone. Cut surface of the resected tumour shows a yellowish-grey tumour with areas of reddish-brown haemorrhage and soft tissue extension.
Undifferentiated pleomorphic sarcoma of bone. Marked cytological pleomorphism characterized by giant tumour cells with large hyperchromatic nuclei.
Undifferentiated pleomorphic sarcoma of bone. Higher power of <<#7567>>Fig. #7567: marked cytological pleomorphism characterized by giant tumour cells with large hyperchromatic nuclei.

Q: Clinically presenting with pain, swelling, and potential pathological fractures in weight-bearing long bones, [...] typically demonstrates an aggressive, predominantly osteolytic lesion with malignant periosteal new bone formation and reddish-brown hemorrhage on gross examination.
Undifferentiated pleomorphic sarcoma of bone. Lateral radiograph shows a predominantly osteolytic lesion in the distal femoral diaphysis, with malignant periosteal new bone formation.
Undifferentiated pleomorphic sarcoma of bone. Sagittal T2-weighted fat-suppressed MRI shows a predominantly osteolytic lesion in the distal femoral diaphysis, with malignant periosteal new bone formation and soft tissue mass anteriorly.
Undifferentiated pleomorphic sarcoma of bone. Cut surface of the resected tumour shows a yellowish-grey tumour with areas of reddish-brown haemorrhage and soft tissue extension.
A: Undifferentiated Pleomorphic Sarcoma of Bone
Back Extra: Undifferentiated Pleomorphic Sarcoma of Bone
- Clinical: Undifferentiated Pleomorphic Sarcoma of Bone typically presents with pain and swelling, and is often associated with pathological fractures in weight-bearing long bones.
- Micro: The tumour is characterized by marked pleomorphism with spindle-shaped and epithelioid cells, multinucleated giant cells, and numerous atypical mitotic figures.
- Ancillary: Immunohistochemistry is crucial for diagnosis, as UPS lacks an identifiable line of differentiation and is a diagnosis of exclusion.
Reference Gallery:
Undifferentiated pleomorphic sarcoma. Marked cytological pleomorphism characterized by giant tumour cells with large hyperchromatic nuclei and atypical mitoses.
Undifferentiated pleomorphic sarcoma of bone. Lateral radiograph shows a predominantly osteolytic lesion in the distal femoral diaphysis, with malignant periosteal new bone formation.
Undifferentiated pleomorphic sarcoma of bone. Sagittal T2-weighted fat-suppressed MRI shows a predominantly osteolytic lesion in the distal femoral diaphysis, with malignant periosteal new bone formation and soft tissue mass anteriorly.
Undifferentiated pleomorphic sarcoma of bone. Cut surface of the resected tumour shows a yellowish-grey tumour with areas of reddish-brown haemorrhage and soft tissue extension.
Undifferentiated pleomorphic sarcoma of bone. Marked cytological pleomorphism characterized by giant tumour cells with large hyperchromatic nuclei.
Undifferentiated pleomorphic sarcoma of bone. Higher power of <<#7567>>Fig. #7567: marked cytological pleomorphism characterized by giant tumour cells with large hyperchromatic nuclei.

Q: On axial CT imaging, a vertebral Haemangioma of bone characteristically presents as a fat-containing lytic lesion with coarse trabeculae, known as the [...].
Haemangioma of bone. CT axial image demonstrates a low-density, fat-containing lytic vertebral lesion with coarse trabeculae, known as the polka-dot pattern.
A: polka-dot pattern
Back Extra: Haemangioma of bone
- Clinical: The majority of haemangiomas, especially those arising in the spine, are incidental radiographic findings. However, large vertebral tumours may cause cord compression, pain, and neurological symptoms.
- Micro: Haemangiomas are composed of thin-walled blood-filled vessels lined by a single layer of flat, cytologically banal endothelial cells, permeating the marrow and surrounding pre-existing trabeculae.
- Ancillary: The tumour cells stain for endothelial markers such as CD31, ERG, FLI1, CD34, and factor VIII–related antigen.
Reference Gallery:
Haemangioma of bone. CT axial image demonstrates a low-density, fat-containing lytic vertebral lesion with coarse trabeculae, known as the polka-dot pattern.
Haemangioma of bone. Portion of tibia with a well-circumscribed tumour showing a solid component and coarse trabeculations.
Haemangioma of bone. Cavernous haemangioma consisting of dilated blood vessels lined by flat banal endothelial cells.

Q: Microscopically, Haemangioma of bone is characteristically composed of dilated, blood-filled vessels lined by a single layer of flat, cytologically banal [...] cells.
Haemangioma of bone. Cavernous haemangioma consisting of dilated blood vessels lined by flat banal endothelial cells.
A: endothelial
Back Extra: Haemangioma of bone
- Clinical: The majority of haemangiomas, especially those arising in the spine, are incidental radiographic findings. However, large vertebral tumours may cause cord compression, pain, and neurological symptoms.
- Micro: Haemangiomas are composed of thin-walled blood-filled vessels lined by a single layer of flat, cytologically banal endothelial cells, permeating the marrow and surrounding pre-existing trabeculae.
- Ancillary: The tumour cells stain for endothelial markers such as CD31, ERG, FLI1, CD34, and factor VIII–related antigen.
Reference Gallery:
Haemangioma of bone. CT axial image demonstrates a low-density, fat-containing lytic vertebral lesion with coarse trabeculae, known as the polka-dot pattern.
Haemangioma of bone. Portion of tibia with a well-circumscribed tumour showing a solid component and coarse trabeculations.
Haemangioma of bone. Cavernous haemangioma consisting of dilated blood vessels lined by flat banal endothelial cells.

Q: A vascular tumor characterized by a lobular proliferation of epithelioid endothelial cells, frequently accompanied by an inflammatory infiltrate rich in eosinophils, is known as [...].
Epithelioid haemangioma of bone. Lobulated architecture with a congeries of arteriole-like structures surrounding tumour.
Epithelioid haemangioma of bone. Epithelioid endothelial cells bulge into well-formed vascular lumina and also grow in solid clusters.
Epithelioid haemangioma of bone. Numerous eosinophils are present within the tumour in a subset of cases.
A: Epithelioid Haemangioma of Bone
Back Extra: Epithelioid Haemangioma of Bone
- Clinical: Epithelioid haemangioma of bone typically presents as a well-defined lytic, sometimes expansile mass in the metaphysis or diaphysis of long tubular bones, causing pain.
- Micro: The tumour has a lobular architecture with large, polyhedral epithelioid cells that form vascular lumina or grow in solid sheets, often with a prominent inflammatory infiltrate rich in eosinophils.
- Ancillary: Immunohistochemistry shows strong positivity for CD31, CD34, and FOSB, with some cases also positive for keratin.
Reference Gallery:
Epithelioid haemangioma of bone. Lytic and expansile mass of the distal clavicle surrounded by a thin rim of reactive bone.
Epithelioid haemangioma of bone. Lobulated mass that is sharply demarcated and shows high signal intensity on axial proton density fat-saturated MRI.
Epithelioid haemangioma of bone. Numerous round, lytic, well-defined lesions in distal radius and ulna.
Epithelioid haemangioma of bone. A dark-red, well-circumscribed tumour arises in the bone and extends into the soft tissue.
Epithelioid haemangioma of bone. Lobulated architecture with a congeries of arteriole-like structures surrounding tumour.
Epithelioid haemangioma of bone. Epithelioid endothelial cells bulge into well-formed vascular lumina and also grow in solid clusters.
Epithelioid haemangioma of bone. Epithelioid endothelial cells with vesicular nuclei and densely eosinophilic cytoplasm that contains vacuoles.
Epithelioid haemangioma of bone. Intratumoural haemorrhage with spindle-shaped neoplastic cells.
Epithelioid haemangioma of bone. Numerous eosinophils are present within the tumour in a subset of cases.
Epithelioid haemangioma of bone. The epithelioid cells stain strongly with CD31 on immunohistochemistry.
Epithelioid haemangioma of bone. The epithelioid cells can stain strongly with keratin.
Epithelioid haemangioma of bone. The epithelioid cells stain strongly with FOSB.

Q: In addition to endothelial markers (e.g., CD31, CD34), Epithelioid Haemangioma of Bone often demonstrates strong nuclear immunohistochemical positivity for [...].
Epithelioid haemangioma of bone. The epithelioid cells stain strongly with CD31 on immunohistochemistry.
Epithelioid haemangioma of bone. The epithelioid cells stain strongly with FOSB.
A: FOSB
Back Extra: Epithelioid Haemangioma of Bone
- Clinical: Epithelioid haemangioma of bone typically presents as a well-defined lytic, sometimes expansile mass in the metaphysis or diaphysis of long tubular bones, causing pain.
- Micro: The tumour has a lobular architecture with large, polyhedral epithelioid cells that form vascular lumina or grow in solid sheets, often with a prominent inflammatory infiltrate rich in eosinophils.
- Ancillary: Immunohistochemistry shows strong positivity for CD31, CD34, and FOSB, with some cases also positive for keratin.
Reference Gallery:
Epithelioid haemangioma of bone. Lytic and expansile mass of the distal clavicle surrounded by a thin rim of reactive bone.
Epithelioid haemangioma of bone. Lobulated mass that is sharply demarcated and shows high signal intensity on axial proton density fat-saturated MRI.
Epithelioid haemangioma of bone. Numerous round, lytic, well-defined lesions in distal radius and ulna.
Epithelioid haemangioma of bone. A dark-red, well-circumscribed tumour arises in the bone and extends into the soft tissue.
Epithelioid haemangioma of bone. Lobulated architecture with a congeries of arteriole-like structures surrounding tumour.
Epithelioid haemangioma of bone. Epithelioid endothelial cells bulge into well-formed vascular lumina and also grow in solid clusters.
Epithelioid haemangioma of bone. Epithelioid endothelial cells with vesicular nuclei and densely eosinophilic cytoplasm that contains vacuoles.
Epithelioid haemangioma of bone. Intratumoural haemorrhage with spindle-shaped neoplastic cells.
Epithelioid haemangioma of bone. Numerous eosinophils are present within the tumour in a subset of cases.
Epithelioid haemangioma of bone. The epithelioid cells stain strongly with CD31 on immunohistochemistry.
Epithelioid haemangioma of bone. The epithelioid cells can stain strongly with keratin.
Epithelioid haemangioma of bone. The epithelioid cells stain strongly with FOSB.

Q: Radiographically, [...] typically presents as a well-defined, sometimes expansile lytic mass in the metaphysis or diaphysis of long tubular bones.
Epithelioid haemangioma of bone. Lytic and expansile mass of the distal clavicle surrounded by a thin rim of reactive bone.
Epithelioid haemangioma of bone. Lobulated mass that is sharply demarcated and shows high signal intensity on axial proton density fat-saturated MRI.
Epithelioid haemangioma of bone. Numerous round, lytic, well-defined lesions in distal radius and ulna.
A: Epithelioid Haemangioma of Bone
Back Extra: Epithelioid Haemangioma of Bone
- Clinical: Epithelioid haemangioma of bone typically presents as a well-defined lytic, sometimes expansile mass in the metaphysis or diaphysis of long tubular bones, causing pain.
- Micro: The tumour has a lobular architecture with large, polyhedral epithelioid cells that form vascular lumina or grow in solid sheets, often with a prominent inflammatory infiltrate rich in eosinophils.
- Ancillary: Immunohistochemistry shows strong positivity for CD31, CD34, and FOSB, with some cases also positive for keratin.
Reference Gallery:
Epithelioid haemangioma of bone. Lytic and expansile mass of the distal clavicle surrounded by a thin rim of reactive bone.
Epithelioid haemangioma of bone. Lobulated mass that is sharply demarcated and shows high signal intensity on axial proton density fat-saturated MRI.
Epithelioid haemangioma of bone. Numerous round, lytic, well-defined lesions in distal radius and ulna.
Epithelioid haemangioma of bone. A dark-red, well-circumscribed tumour arises in the bone and extends into the soft tissue.
Epithelioid haemangioma of bone. Lobulated architecture with a congeries of arteriole-like structures surrounding tumour.
Epithelioid haemangioma of bone. Epithelioid endothelial cells bulge into well-formed vascular lumina and also grow in solid clusters.
Epithelioid haemangioma of bone. Epithelioid endothelial cells with vesicular nuclei and densely eosinophilic cytoplasm that contains vacuoles.
Epithelioid haemangioma of bone. Intratumoural haemorrhage with spindle-shaped neoplastic cells.
Epithelioid haemangioma of bone. Numerous eosinophils are present within the tumour in a subset of cases.
Epithelioid haemangioma of bone. The epithelioid cells stain strongly with CD31 on immunohistochemistry.
Epithelioid haemangioma of bone. The epithelioid cells can stain strongly with keratin.
Epithelioid haemangioma of bone. The epithelioid cells stain strongly with FOSB.

Q: An older patient presents with multiple lytic bone lesions. Grossly, the mass is extensively hemorrhagic, and histopathology reveals malignant cells forming vascular spaces that are strongly positive for CD31, ERG, and FLI1. The most likely diagnosis is [...].
Angiosarcoma of bone. Coronal CT of an angiosarcoma producing multiple lytic lesions involving the femur and pelvic bones.
Angiosarcoma of bone. The tumour infiltrates bone. It forms obvious vascular spaces, with some of the lumina being lined by malignant endothelial cells.
Angiosarcoma of bone. The resected large haemorrhagic tumour involves and destroys several bones, extending into soft tissues.
A: angiosarcoma of bone
Back Extra: Angiosarcoma of Bone
- Clinical: Angiosarcoma of bone is rare, usually presents as a painful lesion, and is more common in older individuals.
- Micro: Characterized by cytologically malignant cells, often epithelioid, with vesicular nuclei and numerous mitotic figures.
- Ancillary: Positive for endothelial markers (ERG, CD31, FLI1) and often shows amplification of 2q and 17q.
Reference Gallery:
Angiosarcoma of bone. Coronal CT of an angiosarcoma producing multiple lytic lesions involving the femur and pelvic bones.
Angiosarcoma of bone. The tumour infiltrates bone. It forms obvious vascular spaces, with some of the lumina being lined by malignant endothelial cells.
Epithelioid angiosarcoma of bone. The tumour cells are epithelioid and form a solid growth pattern, mimicking metastatic carcinoma.
Angiosarcoma of bone. The resected large haemorrhagic tumour involves and destroys several bones, extending into soft tissues.
Angiosarcoma of bone. This tumour shows spindle cell morphology and extravasation of erythrocytes.

Q: Histologically, the epithelioid variant of angiosarcoma of bone often forms a solid growth pattern with large, cytologically malignant cells with vesicular nuclei, a morphology that can closely mimic [...].
Epithelioid angiosarcoma of bone. The tumour cells are epithelioid and form a solid growth pattern, mimicking metastatic carcinoma.
A: metastatic carcinoma
Back Extra: Angiosarcoma of Bone
- Clinical: Angiosarcoma of bone is rare, usually presents as a painful lesion, and is more common in older individuals.
- Micro: Characterized by cytologically malignant cells, often epithelioid, with vesicular nuclei and numerous mitotic figures.
- Ancillary: Positive for endothelial markers (ERG, CD31, FLI1) and often shows amplification of 2q and 17q.
Reference Gallery:
Angiosarcoma of bone. Coronal CT of an angiosarcoma producing multiple lytic lesions involving the femur and pelvic bones.
Angiosarcoma of bone. The tumour infiltrates bone. It forms obvious vascular spaces, with some of the lumina being lined by malignant endothelial cells.
Epithelioid angiosarcoma of bone. The tumour cells are epithelioid and form a solid growth pattern, mimicking metastatic carcinoma.
Angiosarcoma of bone. The resected large haemorrhagic tumour involves and destroys several bones, extending into soft tissues.
Angiosarcoma of bone. This tumour shows spindle cell morphology and extravasation of erythrocytes.

Q: In addition to classic epithelioid and obvious vascular patterns, angiosarcoma of bone can occasionally exhibit a spindle cell morphology associated with prominent extravasation of [...] into the surrounding stroma.
Angiosarcoma of bone. This tumour shows spindle cell morphology and extravasation of erythrocytes.
A: erythrocytes
Back Extra: Angiosarcoma of Bone
- Clinical: Angiosarcoma of bone is rare, usually presents as a painful lesion, and is more common in older individuals.
- Micro: Characterized by cytologically malignant cells, often epithelioid, with vesicular nuclei and numerous mitotic figures.
- Ancillary: Positive for endothelial markers (ERG, CD31, FLI1) and often shows amplification of 2q and 17q.
Reference Gallery:
Angiosarcoma of bone. Coronal CT of an angiosarcoma producing multiple lytic lesions involving the femur and pelvic bones.
Angiosarcoma of bone. The tumour infiltrates bone. It forms obvious vascular spaces, with some of the lumina being lined by malignant endothelial cells.
Epithelioid angiosarcoma of bone. The tumour cells are epithelioid and form a solid growth pattern, mimicking metastatic carcinoma.
Angiosarcoma of bone. The resected large haemorrhagic tumour involves and destroys several bones, extending into soft tissues.
Angiosarcoma of bone. This tumour shows spindle cell morphology and extravasation of erythrocytes.

Q: Radiographically presenting as single or regionally multifocal osteolytic lesions and grossly as large hemorrhagic tumors destroying host tissue, [...] is an aggressive vascular malignancy.
Angiosarcoma of bone. Coronal CT of an angiosarcoma producing multiple lytic lesions involving the femur and pelvic bones.
Angiosarcoma of bone. The resected large haemorrhagic tumour involves and destroys several bones, extending into soft tissues.
A: Angiosarcoma of Bone
Back Extra: Angiosarcoma of Bone
- Clinical: Angiosarcoma of bone typically presents as a painful lesion with a palpable mass, often manifesting as a single or regionally multifocal osteolytic tumour.
- Micro: The tumour cells are most often epithelioid in appearance, with vesicular nuclei, deeply eosinophilic cytoplasm, and frequent mitotic figures.
- Ancillary: Angiosarcoma of bone shows expression of endothelial markers like ERG, CD31, and FLI1, and may also express SMA and D2-40.
Reference Gallery:
Angiosarcoma of bone. Coronal CT of an angiosarcoma producing multiple lytic lesions involving the femur and pelvic bones.
Angiosarcoma of bone. The tumour infiltrates bone. It forms obvious vascular spaces, with some of the lumina being lined by malignant endothelial cells.
Epithelioid angiosarcoma of bone. The tumour cells are epithelioid and form a solid growth pattern, mimicking metastatic carcinoma.
Angiosarcoma of bone. The resected large haemorrhagic tumour involves and destroys several bones, extending into soft tissues.
Angiosarcoma of bone. This tumour shows spindle cell morphology and extravasation of erythrocytes.

Q: Histologically, Angiosarcoma of Bone infiltrates host tissue and forms irregular vascular spaces lined by [...] cells; it can also display a spindle cell morphology with prominent extravasation of erythrocytes.
Angiosarcoma of bone. The tumour infiltrates bone. It forms obvious vascular spaces, with some of the lumina being lined by malignant endothelial cells.
Angiosarcoma of bone. This tumour shows spindle cell morphology and extravasation of erythrocytes.
A: malignant endothelial
Back Extra: Angiosarcoma of Bone
- Clinical: Angiosarcoma of bone typically presents as a painful lesion with a palpable mass, often manifesting as a single or regionally multifocal osteolytic tumour.
- Micro: The tumour cells are most often epithelioid in appearance, with vesicular nuclei, deeply eosinophilic cytoplasm, and frequent mitotic figures.
- Ancillary: Angiosarcoma of bone shows expression of endothelial markers like ERG, CD31, and FLI1, and may also express SMA and D2-40.
Reference Gallery:
Angiosarcoma of bone. Coronal CT of an angiosarcoma producing multiple lytic lesions involving the femur and pelvic bones.
Angiosarcoma of bone. The tumour infiltrates bone. It forms obvious vascular spaces, with some of the lumina being lined by malignant endothelial cells.
Epithelioid angiosarcoma of bone. The tumour cells are epithelioid and form a solid growth pattern, mimicking metastatic carcinoma.
Angiosarcoma of bone. The resected large haemorrhagic tumour involves and destroys several bones, extending into soft tissues.
Angiosarcoma of bone. This tumour shows spindle cell morphology and extravasation of erythrocytes.

Q: The epithelioid variant of Angiosarcoma of Bone forms a solid growth pattern mimicking metastatic carcinoma, but can be distinguished by positive immunohistochemical expression for endothelial markers such as [...].
Epithelioid angiosarcoma of bone. The tumour cells are epithelioid and form a solid growth pattern, mimicking metastatic carcinoma.
A: CD31, ERG, and FLI1
Back Extra: Angiosarcoma of Bone
- Clinical: Angiosarcoma of bone typically presents as a painful lesion with a palpable mass, often manifesting as a single or regionally multifocal osteolytic tumour.
- Micro: The tumour cells are most often epithelioid in appearance, with vesicular nuclei, deeply eosinophilic cytoplasm, and frequent mitotic figures.
- Ancillary: Angiosarcoma of bone shows expression of endothelial markers like ERG, CD31, and FLI1, and may also express SMA and D2-40.
Reference Gallery:
Angiosarcoma of bone. Coronal CT of an angiosarcoma producing multiple lytic lesions involving the femur and pelvic bones.
Angiosarcoma of bone. The tumour infiltrates bone. It forms obvious vascular spaces, with some of the lumina being lined by malignant endothelial cells.
Epithelioid angiosarcoma of bone. The tumour cells are epithelioid and form a solid growth pattern, mimicking metastatic carcinoma.
Angiosarcoma of bone. The resected large haemorrhagic tumour involves and destroys several bones, extending into soft tissues.
Angiosarcoma of bone. This tumour shows spindle cell morphology and extravasation of erythrocytes.

Q: Microscopically, [...] features large epithelioid cells (often containing clear vacuoles) arranged in cords within a characteristic myxohyaline stroma.
Epithelioid haemangioendothelioma of bone. Tumour infiltrates the bone. The neoplastic cells are arranged in cords within a myxohyaline stroma.
Epithelioid haemangioendothelioma of bone. The tumour consists of cords of epithelioid cells with deeply eosinophilic cytoplasm, with some containing clear vacuoles, in a basophilic myxohyaline stroma.
A: epithelioid hemangioendothelioma of bone
Q: Epithelioid Hemangioendothelioma of Bone
- Clinical: Common symptoms of [...] include localized pain and swelling, but the lesions can also be asymptomatic.
- Micro: [...] is characterized by large epithelioid cells with eosinophilic cytoplasm arranged in cords within a myxohyaline stroma.
- Ancillary: [...] is often positive for CAMTA1 and may have the WWTR1-CAMTA1 or YAP1-TFE3 fusion genes.
Reference Gallery:
Epithelioid haemangioendothelioma of bone. Expansile lytic tumour of the distal ulna has a trabeculated pattern.
Epithelioid haemangioendothelioma of bone. Tumour has multinodular growth pattern and has high signal intensity on coronal T2 fat-saturated MRI.
YAP1-TFE3–positive epithelioid haemangioendothelioma of bone. Tumour replaces the marrow in multiple vertebral bodies and has high signal intensity in sagittal T2 MRI. Also note vertebral fractures and epidural extension.
YAP1-TFE3–positive epithelioid haemangioendothelioma of bone. FDG PET showing multiple lesions that have avid FDG uptake.
Epithelioid haemangioendothelioma of bone. Sharply demarcated tan-white mass involving the cortex.
Epithelioid haemangioendothelioma of bone. Tumour infiltrates the bone. The neoplastic cells are arranged in cords within a myxohyaline stroma.
Epithelioid haemangioendothelioma of bone. The tumour consists of cords of epithelioid cells with deeply eosinophilic cytoplasm, with some containing clear vacuoles, in a basophilic myxohyaline stroma.
Epithelioid haemangioendothelioma of bone with YAP1-TFE3 fusion. Tumour shows well-formed lumina and large tumour cells with abundant cytoplasm.
Epithelioid haemangioendothelioma of bone with YAP1-TFE3 fusion. Large tumour cells have voluminous eosinophilic cytoplasm.
Epithelioid haemangioendothelioma of bone. Tumour cells show strong nuclear immunohistochemical staining for CAMTA1.
A: Epithelioid Hemangioendothelioma of Bone; Epithelioid Hemangioendothelioma of Bone; Epithelioid Hemangioendothelioma of Bone

Q: Immunohistochemically, epithelioid hemangioendothelioma of bone typically demonstrates strong nuclear positivity for [...], which correlates with the presence of the WWTR1-CAMTA1 gene fusion.
Epithelioid haemangioendothelioma of bone. Tumour cells show strong nuclear immunohistochemical staining for CAMTA1.
A: CAMTA1
Q: Epithelioid Hemangioendothelioma of Bone
- Clinical: Common symptoms of [...] include localized pain and swelling, but the lesions can also be asymptomatic.
- Micro: [...] is characterized by large epithelioid cells with eosinophilic cytoplasm arranged in cords within a myxohyaline stroma.
- Ancillary: [...] is often positive for CAMTA1 and may have the WWTR1-CAMTA1 or YAP1-TFE3 fusion genes.
Reference Gallery:
Epithelioid haemangioendothelioma of bone. Expansile lytic tumour of the distal ulna has a trabeculated pattern.
Epithelioid haemangioendothelioma of bone. Tumour has multinodular growth pattern and has high signal intensity on coronal T2 fat-saturated MRI.
YAP1-TFE3–positive epithelioid haemangioendothelioma of bone. Tumour replaces the marrow in multiple vertebral bodies and has high signal intensity in sagittal T2 MRI. Also note vertebral fractures and epidural extension.
YAP1-TFE3–positive epithelioid haemangioendothelioma of bone. FDG PET showing multiple lesions that have avid FDG uptake.
Epithelioid haemangioendothelioma of bone. Sharply demarcated tan-white mass involving the cortex.
Epithelioid haemangioendothelioma of bone. Tumour infiltrates the bone. The neoplastic cells are arranged in cords within a myxohyaline stroma.
Epithelioid haemangioendothelioma of bone. The tumour consists of cords of epithelioid cells with deeply eosinophilic cytoplasm, with some containing clear vacuoles, in a basophilic myxohyaline stroma.
Epithelioid haemangioendothelioma of bone with YAP1-TFE3 fusion. Tumour shows well-formed lumina and large tumour cells with abundant cytoplasm.
Epithelioid haemangioendothelioma of bone with YAP1-TFE3 fusion. Large tumour cells have voluminous eosinophilic cytoplasm.
Epithelioid haemangioendothelioma of bone. Tumour cells show strong nuclear immunohistochemical staining for CAMTA1.
A: Epithelioid Hemangioendothelioma of Bone; Epithelioid Hemangioendothelioma of Bone; Epithelioid Hemangioendothelioma of Bone

Q: A distinct variant of epithelioid hemangioendothelioma of bone that demonstrates large tumor cells with voluminous eosinophilic cytoplasm and well-formed vascular lumina is driven by the [...] gene fusion.
Epithelioid haemangioendothelioma of bone with YAP1-TFE3 fusion. Tumour shows well-formed lumina and large tumour cells with abundant cytoplasm.
Epithelioid haemangioendothelioma of bone with YAP1-TFE3 fusion. Large tumour cells have voluminous eosinophilic cytoplasm.
A: YAP1-TFE3
Q: Epithelioid Hemangioendothelioma of Bone
- Clinical: Common symptoms of [...] include localized pain and swelling, but the lesions can also be asymptomatic.
- Micro: [...] is characterized by large epithelioid cells with eosinophilic cytoplasm arranged in cords within a myxohyaline stroma.
- Ancillary: [...] is often positive for CAMTA1 and may have the WWTR1-CAMTA1 or YAP1-TFE3 fusion genes.
Reference Gallery:
Epithelioid haemangioendothelioma of bone. Expansile lytic tumour of the distal ulna has a trabeculated pattern.
Epithelioid haemangioendothelioma of bone. Tumour has multinodular growth pattern and has high signal intensity on coronal T2 fat-saturated MRI.
YAP1-TFE3–positive epithelioid haemangioendothelioma of bone. Tumour replaces the marrow in multiple vertebral bodies and has high signal intensity in sagittal T2 MRI. Also note vertebral fractures and epidural extension.
YAP1-TFE3–positive epithelioid haemangioendothelioma of bone. FDG PET showing multiple lesions that have avid FDG uptake.
Epithelioid haemangioendothelioma of bone. Sharply demarcated tan-white mass involving the cortex.
Epithelioid haemangioendothelioma of bone. Tumour infiltrates the bone. The neoplastic cells are arranged in cords within a myxohyaline stroma.
Epithelioid haemangioendothelioma of bone. The tumour consists of cords of epithelioid cells with deeply eosinophilic cytoplasm, with some containing clear vacuoles, in a basophilic myxohyaline stroma.
Epithelioid haemangioendothelioma of bone with YAP1-TFE3 fusion. Tumour shows well-formed lumina and large tumour cells with abundant cytoplasm.
Epithelioid haemangioendothelioma of bone with YAP1-TFE3 fusion. Large tumour cells have voluminous eosinophilic cytoplasm.
Epithelioid haemangioendothelioma of bone. Tumour cells show strong nuclear immunohistochemical staining for CAMTA1.
A: Epithelioid Hemangioendothelioma of Bone; Epithelioid Hemangioendothelioma of Bone; Epithelioid Hemangioendothelioma of Bone

Q: Angiolipoma is a benign soft tissue tumor that microscopically features mature adipocytes and branching capillaries that frequently contain [...].
Angiolipoma. The lesion consists of mature adipocytes and capillaries, some of which contain microthrombi.
A: fibrin thrombi
Back Extra: Angiolipoma
- Clinical: Angiolipomas are small, painful subcutaneous nodules that commonly appear in the extremities, especially the forearm, and the trunk, typically in individuals in their late 20s.
- Micro: Characterized by mature adipocytes mixed with branching capillary-sized vessels, often containing fibrin thrombi, with more prominent vascularity at the periphery.
- Ancillary: Most angiolipomas show a normal karyotype, but 80% have low-frequency PRKD2 mutations, and rare cases may show chromosome 13 rearrangements.
Reference Gallery:
Angiolipoma. The lesion consists of mature adipocytes and capillaries, some of which contain microthrombi.
Angiolipoma. Cellular angiolipoma, in which the vessels predominate.

Q: Angiolipoma includes a morphologic variant where the branching vascular component predominantly replaces the mature adipocytes, which is termed a [...] angiolipoma.
Angiolipoma. Cellular angiolipoma, in which the vessels predominate.
A: cellular
Back Extra: Angiolipoma
- Clinical: Angiolipomas are small, painful subcutaneous nodules that commonly appear in the extremities, especially the forearm, and the trunk, typically in individuals in their late 20s.
- Micro: Characterized by mature adipocytes mixed with branching capillary-sized vessels, often containing fibrin thrombi, with more prominent vascularity at the periphery.
- Ancillary: Most angiolipomas show a normal karyotype, but 80% have low-frequency PRKD2 mutations, and rare cases may show chromosome 13 rearrangements.
Reference Gallery:
Angiolipoma. The lesion consists of mature adipocytes and capillaries, some of which contain microthrombi.
Angiolipoma. Cellular angiolipoma, in which the vessels predominate.

Q: Angiolipoma generally demonstrates a normal karyotype; however, the majority of cases harbor low-frequency mutations in the [...] gene.
Angiolipoma. The lesion consists of mature adipocytes and capillaries, some of which contain microthrombi.
A: PRKD2
Back Extra: Angiolipoma
- Clinical: Angiolipomas are small, painful subcutaneous nodules that commonly appear in the extremities, especially the forearm, and the trunk, typically in individuals in their late 20s.
- Micro: Characterized by mature adipocytes mixed with branching capillary-sized vessels, often containing fibrin thrombi, with more prominent vascularity at the periphery.
- Ancillary: Most angiolipomas show a normal karyotype, but 80% have low-frequency PRKD2 mutations, and rare cases may show chromosome 13 rearrangements.
Reference Gallery:
Angiolipoma. The lesion consists of mature adipocytes and capillaries, some of which contain microthrombi.
Angiolipoma. Cellular angiolipoma, in which the vessels predominate.

Q: The classic histologic pattern of a [...] consists of multivacuolated brown fat cells with a centrally placed, normochromatic nucleus.
Hibernoma. Classic pattern, consisting of multivacuolated brown fat cells, with a centrally placed, normochromatic nucleus.
A: hibernoma
Back Extra: Hibernoma
- Clinical: Hibernomas typically present as small, slow-growing, painless, mobile, subcutaneous masses in young adults (mean age 38 years).
- Micro: Hibernomas are characterized by multivacuolated brown fat cells with a centrally placed, normochromatic nucleus and a rich capillary network.
- Ancillary: Hibernomas commonly show complex genomic rearrangements involving chromosome 11q13, with deletions affecting the MEN1 and AIP genes.
Reference Gallery:
Hibernoma. Tumour of the abdominal wall, visualized on T2-weighted MRI (top image) and FDG PET (bottom image). Hibernomas are very metabolically active and are often identified incidentally on FDG PET performed for the detection of metastatic disease in patients with known malignancies.
Hibernoma. Multiple hibernomas (yellow ovals), in this instance arising in a patient with documented multiple endocrine neoplasia type 1.
Hibernoma. Classic pattern, consisting of multivacuolated brown fat cells, with a centrally placed, normochromatic nucleus.
Hibernoma. FISH analysis with a whole-chromosome paint probe specific for chromosome 11 reveals complex structural rearrangements involving this chromosome.
Hibernoma. SNP array analysis shows hemizygous and homozygous deletions in chromosome band 11q13. The homozygous deletions contain the genes MEN1 (64.3 Mb) and AIP (67.0 Mb).
Hibernoma. Lipoma-like subtype of hibernoma, consisting chiefly of white fat.
Hibernoma. Spindle cell subtype of hibernoma, with short spindled cells, wiry collagen, and scattered brown fat cells.
Hibernoma. Rare hibernomas occur in an intramuscular location.
Hibernoma. An example with stromal myxoid change and modestly atypical stromal cells. Such tumours are easily mistaken for atypical lipomatous tumour.

Q: A hibernoma commonly exhibits complex genomic rearrangements involving chromosome band [...], which often result in deletions affecting the MEN1 and AIP genes.
Hibernoma. Multiple hibernomas (yellow ovals), in this instance arising in a patient with documented multiple endocrine neoplasia type 1.
Hibernoma. FISH analysis with a whole-chromosome paint probe specific for chromosome 11 reveals complex structural rearrangements involving this chromosome.
Hibernoma. SNP array analysis shows hemizygous and homozygous deletions in chromosome band 11q13. The homozygous deletions contain the genes MEN1 (64.3 Mb) and AIP (67.0 Mb).
A: 11q13
Back Extra: Hibernoma
- Clinical: Hibernomas typically present as small, slow-growing, painless, mobile, subcutaneous masses in young adults (mean age 38 years).
- Micro: Hibernomas are characterized by multivacuolated brown fat cells with a centrally placed, normochromatic nucleus and a rich capillary network.
- Ancillary: Hibernomas commonly show complex genomic rearrangements involving chromosome 11q13, with deletions affecting the MEN1 and AIP genes.
Reference Gallery:
Hibernoma. Tumour of the abdominal wall, visualized on T2-weighted MRI (top image) and FDG PET (bottom image). Hibernomas are very metabolically active and are often identified incidentally on FDG PET performed for the detection of metastatic disease in patients with known malignancies.
Hibernoma. Multiple hibernomas (yellow ovals), in this instance arising in a patient with documented multiple endocrine neoplasia type 1.
Hibernoma. Classic pattern, consisting of multivacuolated brown fat cells, with a centrally placed, normochromatic nucleus.
Hibernoma. FISH analysis with a whole-chromosome paint probe specific for chromosome 11 reveals complex structural rearrangements involving this chromosome.
Hibernoma. SNP array analysis shows hemizygous and homozygous deletions in chromosome band 11q13. The homozygous deletions contain the genes MEN1 (64.3 Mb) and AIP (67.0 Mb).
Hibernoma. Lipoma-like subtype of hibernoma, consisting chiefly of white fat.
Hibernoma. Spindle cell subtype of hibernoma, with short spindled cells, wiry collagen, and scattered brown fat cells.
Hibernoma. Rare hibernomas occur in an intramuscular location.
Hibernoma. An example with stromal myxoid change and modestly atypical stromal cells. Such tumours are easily mistaken for atypical lipomatous tumour.

Q: Due to its composition of [...], a hibernoma typically presents as a highly metabolically active soft tissue mass on FDG PET imaging that can mimic metastatic disease.
Hibernoma. Tumour of the abdominal wall, visualized on T2-weighted MRI (top image) and FDG PET (bottom image). Hibernomas are very metabolically active and are often identified incidentally on FDG PET performed for the detection of metastatic disease in patients with known malignancies.
A: brown fat
Back Extra: Hibernoma
- Clinical: Hibernomas typically present as small, slow-growing, painless, mobile, subcutaneous masses in young adults (mean age 38 years).
- Micro: Hibernomas are characterized by multivacuolated brown fat cells with a centrally placed, normochromatic nucleus and a rich capillary network.
- Ancillary: Hibernomas commonly show complex genomic rearrangements involving chromosome 11q13, with deletions affecting the MEN1 and AIP genes.
Reference Gallery:
Hibernoma. Tumour of the abdominal wall, visualized on T2-weighted MRI (top image) and FDG PET (bottom image). Hibernomas are very metabolically active and are often identified incidentally on FDG PET performed for the detection of metastatic disease in patients with known malignancies.
Hibernoma. Multiple hibernomas (yellow ovals), in this instance arising in a patient with documented multiple endocrine neoplasia type 1.
Hibernoma. Classic pattern, consisting of multivacuolated brown fat cells, with a centrally placed, normochromatic nucleus.
Hibernoma. FISH analysis with a whole-chromosome paint probe specific for chromosome 11 reveals complex structural rearrangements involving this chromosome.
Hibernoma. SNP array analysis shows hemizygous and homozygous deletions in chromosome band 11q13. The homozygous deletions contain the genes MEN1 (64.3 Mb) and AIP (67.0 Mb).
Hibernoma. Lipoma-like subtype of hibernoma, consisting chiefly of white fat.
Hibernoma. Spindle cell subtype of hibernoma, with short spindled cells, wiry collagen, and scattered brown fat cells.
Hibernoma. Rare hibernomas occur in an intramuscular location.
Hibernoma. An example with stromal myxoid change and modestly atypical stromal cells. Such tumours are easily mistaken for atypical lipomatous tumour.

Q: Histologically, Lipoblastoma and Lipoblastomatosis display a characteristic lobulated architecture separated by fibrovascular septa, with a mixture of peripheral myxoid mesenchymal tissue in transition with adipocytic tissue containing varying stages of [...].
Lipoblastoma. This circumscribed, lobulated mass shows internal fibrous septa with a mixture of peripheral myxoid mesenchymal tissue in transition with adipocytic tissue, containing lipoblasts in various stages of maturation.
Lipoblastoma. Lipoblasts display a range of maturation, from multivacuolated lipoblasts to small signet-ring lipoblasts to mature adipocytes.
A: lipoblasts
Back Extra: Lipoblastoma and Lipoblastomatosis
- Clinical: Lipoblastoma and Lipoblastomatosis are benign adipocytic neoplasms that can present as superficial circumscribed masses or infiltrative deep soft tissue tumours, often in the trunk, and can cause compressive symptoms such as stridor.
- Micro: Characterized by a lobulated architecture with sheets of adipocytes separated by fibrovascular septa, ranging from primitive mesenchymal cells to mature adipocytes.
- Ancillary: PLAG1 rearrangements, often involving chromosome 8q11-q13, can support the diagnosis and are detected using FISH or karyotyping.
Reference Gallery:
Lipoblastoma. FISH analysis performed on metaphase cells of this case using a PLAG1 break-apart probe set revealed the presence of two abnormal chromosome 8 homologues with a cytogenetically cryptic paracentric inversion resulting in PLAG1 rearrangement (arrows). Normal chromosome 8 with juxtaposed orange/green signals (arrowhead).
Lipoblastoma. R-banded karyotype of a lipoblastoma showing polysomy of chromosome 8.
Lipoblastoma. This circumscribed, lobulated mass shows internal fibrous septa with a mixture of peripheral myxoid mesenchymal tissue in transition with adipocytic tissue, containing lipoblasts in various stages of maturation.
Lipoblastoma. Lipoblasts display a range of maturation, from multivacuolated lipoblasts to small signet-ring lipoblasts to mature adipocytes.
Lipoblastoma. A myxoid area of lipoblastoma highlighting the delicate vasculature, myxoid matrix, and mesenchymal spindle cell component, which may occasionally include mild to moderate nuclear atypia.
Lipoblastoma. Mature lipoblastoma resembles fibrolipoma, with delicate internal fibrous septa, mostly mature adipocytes, and rare lipoblasts, most readily identified at the edges of the lobules, adjacent to foci of myxoid stroma.

Q: Molecular analysis of Lipoblastoma and Lipoblastomatosis frequently reveals characteristic genetic rearrangements in the [...] gene on chromosome 8q11-q13, which can be detected using FISH or karyotyping.
Lipoblastoma. FISH analysis performed on metaphase cells of this case using a PLAG1 break-apart probe set revealed the presence of two abnormal chromosome 8 homologues with a cytogenetically cryptic paracentric inversion resulting in PLAG1 rearrangement (arrows). Normal chromosome 8 with juxtaposed orange/green signals (arrowhead).
Lipoblastoma. R-banded karyotype of a lipoblastoma showing polysomy of chromosome 8.
A: PLAG1
Back Extra: Lipoblastoma and Lipoblastomatosis
- Clinical: Lipoblastoma and Lipoblastomatosis are benign adipocytic neoplasms that can present as superficial circumscribed masses or infiltrative deep soft tissue tumours, often in the trunk, and can cause compressive symptoms such as stridor.
- Micro: Characterized by a lobulated architecture with sheets of adipocytes separated by fibrovascular septa, ranging from primitive mesenchymal cells to mature adipocytes.
- Ancillary: PLAG1 rearrangements, often involving chromosome 8q11-q13, can support the diagnosis and are detected using FISH or karyotyping.
Reference Gallery:
Lipoblastoma. FISH analysis performed on metaphase cells of this case using a PLAG1 break-apart probe set revealed the presence of two abnormal chromosome 8 homologues with a cytogenetically cryptic paracentric inversion resulting in PLAG1 rearrangement (arrows). Normal chromosome 8 with juxtaposed orange/green signals (arrowhead).
Lipoblastoma. R-banded karyotype of a lipoblastoma showing polysomy of chromosome 8.
Lipoblastoma. This circumscribed, lobulated mass shows internal fibrous septa with a mixture of peripheral myxoid mesenchymal tissue in transition with adipocytic tissue, containing lipoblasts in various stages of maturation.
Lipoblastoma. Lipoblasts display a range of maturation, from multivacuolated lipoblasts to small signet-ring lipoblasts to mature adipocytes.
Lipoblastoma. A myxoid area of lipoblastoma highlighting the delicate vasculature, myxoid matrix, and mesenchymal spindle cell component, which may occasionally include mild to moderate nuclear atypia.
Lipoblastoma. Mature lipoblastoma resembles fibrolipoma, with delicate internal fibrous septa, mostly mature adipocytes, and rare lipoblasts, most readily identified at the edges of the lobules, adjacent to foci of myxoid stroma.

Q: Focally, Chondroid Lipoma can show a prominent vascular pattern of arborizing capillaries, which may histologically mimic [...].
Chondroid lipoma. Focally, chondroid lipomas can show arborizing capillaries, simulating myxoid liposarcoma.
A: myxoid liposarcoma
Back Extra: Chondroid Lipoma
- Clinical: Chondroid lipomas are typically found as painless, well-circumscribed masses, predominantly in adult women.
- Micro: Histologically, these tumours show a mixture of mature adipocytes, lipoblasts, and a myxohyaline chondroid matrix, often with arborizing capillaries.
- Ancillary: The characteristic t(11;16)(q13;p13) translocation results in the C11orf95-MRTFB fusion gene, a key diagnostic marker.
Reference Gallery:
Chondroid lipoma. These tumours present as small, well-circumscribed or even encapsulated masses.
Chondroid lipoma. The tumour consists of a moderately cellular proliferation of epithelioid cells, lipoblasts, and mature fat, in a hyalinized, vaguely chondroid matrix.
Chondroid lipoma. Focally, chondroid lipomas can show arborizing capillaries, simulating myxoid liposarcoma.
Chondroid lipoma. High-power view of lipoblasts, mature fat, and hyalinized stroma in chondroid lipoma.
Genetics of chondroid lipoma. A Partial karyotype and schematic illustrating the characteristic 11;16 translocation. B Schematic of C11orf95 and MRTFB showing corresponding breakpoints associated with the C11orf95-MRTFB fusion gene. C Nucleotide and amino acid sequences around the fusion point are presented. D The coding region of the fusion cDNA demonstrating the boundaries of exons and the position of conserved domains.

Q: The defining molecular feature of Chondroid Lipoma is a t(11;16) translocation resulting in the [...] fusion gene.
Genetics of chondroid lipoma. A Partial karyotype and schematic illustrating the characteristic 11;16 translocation. B Schematic of C11orf95 and MRTFB showing corresponding breakpoints associated with the C11orf95-MRTFB fusion gene. C Nucleotide and amino acid sequences around the fusion point are presented. D The coding region of the fusion cDNA demonstrating the boundaries of exons and the position of conserved domains.
A: C11orf95-MRTFB
Back Extra: Chondroid Lipoma
- Clinical: Chondroid lipomas are typically found as painless, well-circumscribed masses, predominantly in adult women.
- Micro: Histologically, these tumours show a mixture of mature adipocytes, lipoblasts, and a myxohyaline chondroid matrix, often with arborizing capillaries.
- Ancillary: The characteristic t(11;16)(q13;p13) translocation results in the C11orf95-MRTFB fusion gene, a key diagnostic marker.
Reference Gallery:
Chondroid lipoma. These tumours present as small, well-circumscribed or even encapsulated masses.
Chondroid lipoma. The tumour consists of a moderately cellular proliferation of epithelioid cells, lipoblasts, and mature fat, in a hyalinized, vaguely chondroid matrix.
Chondroid lipoma. Focally, chondroid lipomas can show arborizing capillaries, simulating myxoid liposarcoma.
Chondroid lipoma. High-power view of lipoblasts, mature fat, and hyalinized stroma in chondroid lipoma.
Genetics of chondroid lipoma. A Partial karyotype and schematic illustrating the characteristic 11;16 translocation. B Schematic of C11orf95 and MRTFB showing corresponding breakpoints associated with the C11orf95-MRTFB fusion gene. C Nucleotide and amino acid sequences around the fusion point are presented. D The coding region of the fusion cDNA demonstrating the boundaries of exons and the position of conserved domains.

Q: Histologically, Chondroid Lipoma is a well-circumscribed tumor composed of epithelioid cells, mature fat, and [...] embedded in a myxohyaline, vaguely chondroid matrix.
Chondroid lipoma. These tumours present as small, well-circumscribed or even encapsulated masses.
Chondroid lipoma. The tumour consists of a moderately cellular proliferation of epithelioid cells, lipoblasts, and mature fat, in a hyalinized, vaguely chondroid matrix.
Chondroid lipoma. High-power view of lipoblasts, mature fat, and hyalinized stroma in chondroid lipoma.
A: lipoblasts
Back Extra: Chondroid Lipoma
- Clinical: Chondroid lipomas are typically found as painless, well-circumscribed masses, predominantly in adult women.
- Micro: Histologically, these tumours show a mixture of mature adipocytes, lipoblasts, and a myxohyaline chondroid matrix, often with arborizing capillaries.
- Ancillary: The characteristic t(11;16)(q13;p13) translocation results in the C11orf95-MRTFB fusion gene, a key diagnostic marker.
Reference Gallery:
Chondroid lipoma. These tumours present as small, well-circumscribed or even encapsulated masses.
Chondroid lipoma. The tumour consists of a moderately cellular proliferation of epithelioid cells, lipoblasts, and mature fat, in a hyalinized, vaguely chondroid matrix.
Chondroid lipoma. Focally, chondroid lipomas can show arborizing capillaries, simulating myxoid liposarcoma.
Chondroid lipoma. High-power view of lipoblasts, mature fat, and hyalinized stroma in chondroid lipoma.
Genetics of chondroid lipoma. A Partial karyotype and schematic illustrating the characteristic 11;16 translocation. B Schematic of C11orf95 and MRTFB showing corresponding breakpoints associated with the C11orf95-MRTFB fusion gene. C Nucleotide and amino acid sequences around the fusion point are presented. D The coding region of the fusion cDNA demonstrating the boundaries of exons and the position of conserved domains.

Q: Histological examination of a Lipoma classically reveals a homogeneous proliferation of [...] lacking cytological atypia.
Lipoma. Histological sections show a homogeneous population of mature adipocytes.
A: mature adipocytes
Back Extra: Lipoma
- Clinical: Lipomas typically present as painless masses, but larger tumours may compress peripheral nerves, causing pain or tenderness.
- Micro: Histological examination reveals a well-differentiated lipomatous proliferation composed of mature adipocytes, with no cytological atypia.
- Ancillary: Diagnostic molecular pathology is not usually required, but in deep-seated or large tumours, the exclusion of MDM2 amplification is necessary.
Reference Gallery:
Lipoma. Histological sections show a homogeneous population of mature adipocytes.
Intramuscular lipoma. These often show skeletal muscle fibres surrounded by mature adipocytes.
Intramuscular lipoma. Atrophic skeletal muscle in intramuscular lipoma can mimic the atypical hyperchromatic stromal cells of atypical lipomatous tumour/well-differentiated liposarcoma.
Osteolipoma. These tumours contain nodules of metaplastic bone and cartilage.
Lipoma. Gross examination shows a glistening yellowish-tan cut surface.

Q: On gross examination, a typical Lipoma presents as a well-circumscribed mass exhibiting a glistening, [...] cut surface.
Lipoma. Gross examination shows a glistening yellowish-tan cut surface.
A: yellowish-tan
Back Extra: Lipoma
- Clinical: Lipomas typically present as painless masses, but larger tumours may compress peripheral nerves, causing pain or tenderness.
- Micro: Histological examination reveals a well-differentiated lipomatous proliferation composed of mature adipocytes, with no cytological atypia.
- Ancillary: Diagnostic molecular pathology is not usually required, but in deep-seated or large tumours, the exclusion of MDM2 amplification is necessary.
Reference Gallery:
Lipoma. Histological sections show a homogeneous population of mature adipocytes.
Intramuscular lipoma. These often show skeletal muscle fibres surrounded by mature adipocytes.
Intramuscular lipoma. Atrophic skeletal muscle in intramuscular lipoma can mimic the atypical hyperchromatic stromal cells of atypical lipomatous tumour/well-differentiated liposarcoma.
Osteolipoma. These tumours contain nodules of metaplastic bone and cartilage.
Lipoma. Gross examination shows a glistening yellowish-tan cut surface.

Q: In an intramuscular Lipoma, entrapped atrophic [...] fibers can mimic the atypical hyperchromatic stromal cells of an atypical lipomatous tumor.
Intramuscular lipoma. These often show skeletal muscle fibres surrounded by mature adipocytes.
Intramuscular lipoma. Atrophic skeletal muscle in intramuscular lipoma can mimic the atypical hyperchromatic stromal cells of atypical lipomatous tumour/well-differentiated liposarcoma.
A: skeletal muscle
Back Extra: Lipoma
- Clinical: Lipomas typically present as painless masses, but larger tumours may compress peripheral nerves, causing pain or tenderness.
- Micro: Histological examination reveals a well-differentiated lipomatous proliferation composed of mature adipocytes, with no cytological atypia.
- Ancillary: Diagnostic molecular pathology is not usually required, but in deep-seated or large tumours, the exclusion of MDM2 amplification is necessary.
Reference Gallery:
Lipoma. Histological sections show a homogeneous population of mature adipocytes.
Intramuscular lipoma. These often show skeletal muscle fibres surrounded by mature adipocytes.
Intramuscular lipoma. Atrophic skeletal muscle in intramuscular lipoma can mimic the atypical hyperchromatic stromal cells of atypical lipomatous tumour/well-differentiated liposarcoma.
Osteolipoma. These tumours contain nodules of metaplastic bone and cartilage.
Lipoma. Gross examination shows a glistening yellowish-tan cut surface.

Q: Histologically, the lesions of Spindle Cell Lipoma and Pleomorphic Lipoma frequently feature a characteristic triad of mature adipocytes, bland spindle cells, and thick bundles of eosinophilic [...].
Spindle cell lipoma. This example contains bland spindle cells, ropy collagen, and mature adipocytes.
Spindle cell lipoma. Fat-free subtype of spindle cell lipoma with bland spindle cells and ropy collagen.
A: ropy collagen
Back Extra: Spindle Cell Lipoma and Pleomorphic Lipoma
- Clinical: Spindle cell lipomas and pleomorphic lipomas typically present as painless, slow-growing, solitary, mobile masses in the subcutis, most commonly in the posterior neck, back, and shoulders.
- Micro: The lesions are characterized by a triad of bland spindle cells, mature adipocytes, and ropy collagen bundles. Pleomorphic lipomas additionally contain pleomorphic spindle cells and multinucleated floret-like giant cells.
- Ancillary: Loss of the RB1 locus, particularly 13q14, is characteristic of these tumours. CD34 and loss of nuclear RB1 protein expression in spindle and giant cells are also notable findings.
Reference Gallery:
Spindle cell lipoma. This example contains bland spindle cells, ropy collagen, and mature adipocytes.
Spindle cell lipoma. Some examples have prominent myxoid stroma.
Spindle cell lipoma. Fat-free subtype of spindle cell lipoma with bland spindle cells and ropy collagen.
Spindle cell lipoma. Pseudoangiomatous subtype of spindle cell lipoma.
Pleomorphic lipoma. Typical example with floret-like giant cells admixed with bland spindle cells, ropy collagen, and mature adipocytes.

Q: Within the spectrum of Spindle Cell Lipoma and Pleomorphic Lipoma, the pleomorphic variant is classically distinguished by the presence of pleomorphic spindle cells and characteristic multinucleated [...] giant cells.
Pleomorphic lipoma. Typical example with floret-like giant cells admixed with bland spindle cells, ropy collagen, and mature adipocytes.
A: floret-like
Back Extra: Spindle Cell Lipoma and Pleomorphic Lipoma
- Clinical: Spindle cell lipomas and pleomorphic lipomas typically present as painless, slow-growing, solitary, mobile masses in the subcutis, most commonly in the posterior neck, back, and shoulders.
- Micro: The lesions are characterized by a triad of bland spindle cells, mature adipocytes, and ropy collagen bundles. Pleomorphic lipomas additionally contain pleomorphic spindle cells and multinucleated floret-like giant cells.
- Ancillary: Loss of the RB1 locus, particularly 13q14, is characteristic of these tumours. CD34 and loss of nuclear RB1 protein expression in spindle and giant cells are also notable findings.
Reference Gallery:
Spindle cell lipoma. This example contains bland spindle cells, ropy collagen, and mature adipocytes.
Spindle cell lipoma. Some examples have prominent myxoid stroma.
Spindle cell lipoma. Fat-free subtype of spindle cell lipoma with bland spindle cells and ropy collagen.
Spindle cell lipoma. Pseudoangiomatous subtype of spindle cell lipoma.
Pleomorphic lipoma. Typical example with floret-like giant cells admixed with bland spindle cells, ropy collagen, and mature adipocytes.

Q: Microscopic examination of diffuse Lipomatosis typically reveals lobules and sheets of [...] that infiltratively replace adjacent structures such as skeletal muscle.
Lipomatosis. Mature white fat infiltrating skeletal muscle in diffuse lipomatosis.
Lipomatosis. Adipose tissue infiltrating and replacing much of the involved skeletal muscle.
A: mature adipocytes
Q: Lipomatosis
- Clinical: Patients with [...] can have neuropathy and involvement of the CNS.
- Micro: Histologically, all types of [...] show lobules and sheets of mature adipocytes that may infiltrate other structures such as skeletal muscle.
- Ancillary: Imaging is crucial in [...] to show the extent of fat accumulation and exclude other processes.
Reference Gallery:
Lipomatosis. Mature white fat infiltrating skeletal muscle in diffuse lipomatosis.
Lipomatosis. Adipose tissue infiltrating and replacing much of the involved skeletal muscle.
Multiple symmetrical lipomatosis. Clinical photograph of an adult male patient with multiple symmetrical lipomatosis.
A: symmetrical lipomatosis; lipomatosis; lipomatosis

Q: The clinical variant of Lipomatosis characterized by massive, non-encapsulated fat deposits around the neck and upper trunk (as seen clinically) that may be associated with neuropathy is termed multiple [...] lipomatosis.
Multiple symmetrical lipomatosis. Clinical photograph of an adult male patient with multiple symmetrical lipomatosis.
A: symmetrical
Q: Lipomatosis
- Clinical: Patients with [...] can have neuropathy and involvement of the CNS.
- Micro: Histologically, all types of [...] show lobules and sheets of mature adipocytes that may infiltrate other structures such as skeletal muscle.
- Ancillary: Imaging is crucial in [...] to show the extent of fat accumulation and exclude other processes.
Reference Gallery:
Lipomatosis. Mature white fat infiltrating skeletal muscle in diffuse lipomatosis.
Lipomatosis. Adipose tissue infiltrating and replacing much of the involved skeletal muscle.
Multiple symmetrical lipomatosis. Clinical photograph of an adult male patient with multiple symmetrical lipomatosis.
A: symmetrical lipomatosis; lipomatosis; lipomatosis

Q: Histologically, marked expansion of the epineurium by mature adipose tissue separating widely spaced nerve fascicles, often with perineurial thickening, is characteristic of [...].
Lipomatosis of nerve. The endoneurium is expanded by mature fibroadipose tissue, which separates nerve fascicles. Inset: The perineurium of small nerve fascicles is markedly thickened.
A: Lipomatosis of nerve
Q: Lipomatosis of nerve
- Clinical: Sensory loss and paraesthesias are the most common symptoms of [...], followed by pain and muscle weakness.
- Micro: On microscopic examination, the epineurium of [...] is markedly expanded by mature adipose tissue, and nerve fascicles are widely spaced with frequent perineurial thickening.
- Ancillary: PIK3CA mutations have been reported in patients with [...]-associated macrodactyly.
Reference Gallery:
Lipomatosis of nerve. MRI. Left ulnar-sided fourth digital nerve (arrow) is enlarged (6 mm) and shows a coaxial cable–like appearance.
Lipomatosis of nerve. MRI. The sciatic nerve (arrow) is markedly enlarged (4 cm) and shows a typical coaxial cable–like appearance in this cross-section at the level of the thigh.
Lipomatosis of nerve. Longitudinal MRI. The sciatic nerve (arrow) is markedly enlarged (4 cm) and shows a typical spaghetti-like appearance in this longitudinal section at the level of the thigh.
Lipomatosis of nerve. Intraoperative appearance. The fourth digital nerve is enlarged (6 mm) and shows a yellow lobulated appearance over a 2 cm length, typical of lipomatosis of nerve.
Lipomatosis of nerve. The endoneurium is expanded by mature fibroadipose tissue, which separates nerve fascicles. Inset: The perineurium of small nerve fascicles is markedly thickened.
Lipomatosis of nerve. Endoneurial pseudo–onion bulb–like hypertrophic change.
A: lipomatosis of nerve; lipomatosis of nerve; lipomatosis of nerve

Q: On MRI, Lipomatosis of nerve classically demonstrates a markedly enlarged nerve with a highly characteristic [...]-like appearance on cross-section (or a spaghetti-like appearance longitudinally).
Lipomatosis of nerve. MRI. The sciatic nerve (arrow) is markedly enlarged (4 cm) and shows a typical coaxial cable–like appearance in this cross-section at the level of the thigh.
Lipomatosis of nerve. Longitudinal MRI. The sciatic nerve (arrow) is markedly enlarged (4 cm) and shows a typical spaghetti-like appearance in this longitudinal section at the level of the thigh.
A: coaxial cable
Q: Lipomatosis of nerve
- Clinical: Sensory loss and paraesthesias are the most common symptoms of [...], followed by pain and muscle weakness.
- Micro: On microscopic examination, the epineurium of [...] is markedly expanded by mature adipose tissue, and nerve fascicles are widely spaced with frequent perineurial thickening.
- Ancillary: PIK3CA mutations have been reported in patients with [...]-associated macrodactyly.
Reference Gallery:
Lipomatosis of nerve. MRI. Left ulnar-sided fourth digital nerve (arrow) is enlarged (6 mm) and shows a coaxial cable–like appearance.
Lipomatosis of nerve. MRI. The sciatic nerve (arrow) is markedly enlarged (4 cm) and shows a typical coaxial cable–like appearance in this cross-section at the level of the thigh.
Lipomatosis of nerve. Longitudinal MRI. The sciatic nerve (arrow) is markedly enlarged (4 cm) and shows a typical spaghetti-like appearance in this longitudinal section at the level of the thigh.
Lipomatosis of nerve. Intraoperative appearance. The fourth digital nerve is enlarged (6 mm) and shows a yellow lobulated appearance over a 2 cm length, typical of lipomatosis of nerve.
Lipomatosis of nerve. The endoneurium is expanded by mature fibroadipose tissue, which separates nerve fascicles. Inset: The perineurium of small nerve fascicles is markedly thickened.
Lipomatosis of nerve. Endoneurial pseudo–onion bulb–like hypertrophic change.
A: lipomatosis of nerve; lipomatosis of nerve; lipomatosis of nerve

Q: Microscopically, Myolipoma of Soft Tissue is characterized by an intimate admixture of mature adipocytes and well-differentiated [...] cells arranged in intersecting fascicles without cytological atypia.
Myolipoma. The tumour is composed of an intimate admixture of adipocytes and smooth muscle cells.
Myolipoma. No atypia or mitotic activity is observed in either adipocytes or smooth muscle cells.
A: smooth muscle
Back Extra: Myolipoma of Soft Tissue
- Clinical: Myolipoma of soft tissue is often found incidentally in the abdominal cavity, while those in the trunk or extremities are palpable. MRI shows a fatty mass with associated signal-rich areas.
- Micro: The lesion is composed of mature fat cells and well-differentiated smooth muscle cells, with intersecting fascicles of cytologically bland spindled cells and no atypia or mitotic activity.
- Ancillary: Cytogenetic alterations of the HMGA2 gene and fusion of the HMGA2 and C9orf92 genes have been reported in cases of myolipoma.
Reference Gallery:
Myolipoma. The tumour is composed of an intimate admixture of adipocytes and smooth muscle cells.
Myolipoma. No atypia or mitotic activity is observed in either adipocytes or smooth muscle cells.
Myolipoma. Smooth muscle cells within the tumour show diffuse positivity for desmin.
Myolipoma. Both smooth muscle cells and adipocytes often show nuclear positivity for HMGA2.

Q: In Myolipoma of Soft Tissue, the spindled cellular component demonstrates diffuse immunohistochemical positivity for [...], while both the spindled cells and adipocytes frequently show nuclear positivity for HMGA2.
Myolipoma. Smooth muscle cells within the tumour show diffuse positivity for desmin.
Myolipoma. Both smooth muscle cells and adipocytes often show nuclear positivity for HMGA2.
A: desmin
Back Extra: Myolipoma of Soft Tissue
- Clinical: Myolipoma of soft tissue is often found incidentally in the abdominal cavity, while those in the trunk or extremities are palpable. MRI shows a fatty mass with associated signal-rich areas.
- Micro: The lesion is composed of mature fat cells and well-differentiated smooth muscle cells, with intersecting fascicles of cytologically bland spindled cells and no atypia or mitotic activity.
- Ancillary: Cytogenetic alterations of the HMGA2 gene and fusion of the HMGA2 and C9orf92 genes have been reported in cases of myolipoma.
Reference Gallery:
Myolipoma. The tumour is composed of an intimate admixture of adipocytes and smooth muscle cells.
Myolipoma. No atypia or mitotic activity is observed in either adipocytes or smooth muscle cells.
Myolipoma. Smooth muscle cells within the tumour show diffuse positivity for desmin.
Myolipoma. Both smooth muscle cells and adipocytes often show nuclear positivity for HMGA2.

Q: The essential histologic diagnostic feature of Atypical Lipomatous Tumor / Well-Differentiated Liposarcoma is striking variation in adipocyte size combined with the presence of scattered [...].
Atypical lipomatous tumour / well-differentiated liposarcoma. Striking variation in adipocytic size is a typical feature.
Atypical lipomatous tumour / well-differentiated liposarcoma. The presence of atypical, hyperchromatic stromal cells is an essential diagnostic feature.
A: atypical, hyperchromatic stromal cells
Back Extra: Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma
- Clinical: Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma usually presents as a deep-seated, painless mass, often in the retroperitoneum, where it can grow to a very large size.
- Micro: The histological hallmark of Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma is the presence of atypical, hyperchromatic stromal cells and adipocytes with significant nuclear atypia.
- Ancillary: Detection of MDM2 and/or CDK4 amplification is crucial in distinguishing Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma from benign lipomas.
Reference Gallery:
Atypical lipomatous tumour / well-differentiated liposarcoma. Surgical specimen showing a well-circumscribed, lobulated, yellow mass.
Atypical lipomatous tumour / well-differentiated liposarcoma. Striking variation in adipocytic size is a typical feature.
Atypical lipomatous tumour / well-differentiated liposarcoma. The presence of atypical, hyperchromatic stromal cells is an essential diagnostic feature.
Atypical lipomatous tumour / well-differentiated liposarcoma. A variable number of lipoblasts can be seen in atypical lipomatous tumour / well-differentiated liposarcoma; however, their presence neither makes nor is required for a diagnosis of liposarcoma.
Atypical lipomatous tumour / well-differentiated liposarcoma. The presence of scattered bizarre stromal cells exhibiting marked nuclear hyperchromasia set in a fibrillary collagenous background represents an important diagnostic feature of the sclerosing subtype.
Atypical lipomatous tumour / well-differentiated liposarcoma. In the inflammatory subtype, an abundant chronic inflammatory infiltrate may predominate. Scattered bizarre stromal cells are present.
Atypical lipomatous tumour / well-differentiated liposarcoma. If the inflammatory component predominates, the identification of hyperchromatic, atypical stromal cells represents the most useful diagnostic clue.
Atypical lipomatous tumour / well-differentiated liposarcoma. Genomic quantitative profile obtained by array comparative genomic hybridization. The profile is simple, showing the characteristic 12q14-q15 amplification including MDM2 (black arrow). Amplification of 1q23-q24 and 2q11-q13 is also observed in this case (blue arrows).
Atypical lipomatous tumour / well-differentiated liposarcoma. Interphase FISH using probes for MDM2 (green signal) and centromere of chromosome 12 (red signal) showing high-level amplification of MDM2 grouped in clusters.
Atypical lipomatous tumour / well-differentiated liposarcoma. RHG-banded near-diploid karyotype. The sole chromosomal anomaly is the presence of a supernumerary ring chromosome (arrow).

Q: To distinguish Atypical Lipomatous Tumor / Well-Differentiated Liposarcoma from a benign lipoma, ancillary testing often relies on identifying high-level amplification of the [...] (and/or CDK4) gene.
Atypical lipomatous tumour / well-differentiated liposarcoma. Genomic quantitative profile obtained by array comparative genomic hybridization. The profile is simple, showing the characteristic 12q14-q15 amplification including MDM2 (black arrow). Amplification of 1q23-q24 and 2q11-q13 is also observed in this case (blue arrows).
Atypical lipomatous tumour / well-differentiated liposarcoma. Interphase FISH using probes for MDM2 (green signal) and centromere of chromosome 12 (red signal) showing high-level amplification of MDM2 grouped in clusters.
A: MDM2
Back Extra: Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma
- Clinical: Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma usually presents as a deep-seated, painless mass, often in the retroperitoneum, where it can grow to a very large size.
- Micro: The histological hallmark of Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma is the presence of atypical, hyperchromatic stromal cells and adipocytes with significant nuclear atypia.
- Ancillary: Detection of MDM2 and/or CDK4 amplification is crucial in distinguishing Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma from benign lipomas.
Reference Gallery:
Atypical lipomatous tumour / well-differentiated liposarcoma. Surgical specimen showing a well-circumscribed, lobulated, yellow mass.
Atypical lipomatous tumour / well-differentiated liposarcoma. Striking variation in adipocytic size is a typical feature.
Atypical lipomatous tumour / well-differentiated liposarcoma. The presence of atypical, hyperchromatic stromal cells is an essential diagnostic feature.
Atypical lipomatous tumour / well-differentiated liposarcoma. A variable number of lipoblasts can be seen in atypical lipomatous tumour / well-differentiated liposarcoma; however, their presence neither makes nor is required for a diagnosis of liposarcoma.
Atypical lipomatous tumour / well-differentiated liposarcoma. The presence of scattered bizarre stromal cells exhibiting marked nuclear hyperchromasia set in a fibrillary collagenous background represents an important diagnostic feature of the sclerosing subtype.
Atypical lipomatous tumour / well-differentiated liposarcoma. In the inflammatory subtype, an abundant chronic inflammatory infiltrate may predominate. Scattered bizarre stromal cells are present.
Atypical lipomatous tumour / well-differentiated liposarcoma. If the inflammatory component predominates, the identification of hyperchromatic, atypical stromal cells represents the most useful diagnostic clue.
Atypical lipomatous tumour / well-differentiated liposarcoma. Genomic quantitative profile obtained by array comparative genomic hybridization. The profile is simple, showing the characteristic 12q14-q15 amplification including MDM2 (black arrow). Amplification of 1q23-q24 and 2q11-q13 is also observed in this case (blue arrows).
Atypical lipomatous tumour / well-differentiated liposarcoma. Interphase FISH using probes for MDM2 (green signal) and centromere of chromosome 12 (red signal) showing high-level amplification of MDM2 grouped in clusters.
Atypical lipomatous tumour / well-differentiated liposarcoma. RHG-banded near-diploid karyotype. The sole chromosomal anomaly is the presence of a supernumerary ring chromosome (arrow).

Q: Cytogenetically, Atypical Lipomatous Tumor / Well-Differentiated Liposarcoma is classically associated with the presence of supernumerary [...], which harbor the characteristic 12q14-q15 amplicon.
Atypical lipomatous tumour / well-differentiated liposarcoma. RHG-banded near-diploid karyotype. The sole chromosomal anomaly is the presence of a supernumerary ring chromosome (arrow).
A: ring chromosomes
Back Extra: Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma
- Clinical: Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma usually presents as a deep-seated, painless mass, often in the retroperitoneum, where it can grow to a very large size.
- Micro: The histological hallmark of Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma is the presence of atypical, hyperchromatic stromal cells and adipocytes with significant nuclear atypia.
- Ancillary: Detection of MDM2 and/or CDK4 amplification is crucial in distinguishing Atypical Lipomatous Tumour / Well-Differentiated Liposarcoma from benign lipomas.
Reference Gallery:
Atypical lipomatous tumour / well-differentiated liposarcoma. Surgical specimen showing a well-circumscribed, lobulated, yellow mass.
Atypical lipomatous tumour / well-differentiated liposarcoma. Striking variation in adipocytic size is a typical feature.
Atypical lipomatous tumour / well-differentiated liposarcoma. The presence of atypical, hyperchromatic stromal cells is an essential diagnostic feature.
Atypical lipomatous tumour / well-differentiated liposarcoma. A variable number of lipoblasts can be seen in atypical lipomatous tumour / well-differentiated liposarcoma; however, their presence neither makes nor is required for a diagnosis of liposarcoma.
Atypical lipomatous tumour / well-differentiated liposarcoma. The presence of scattered bizarre stromal cells exhibiting marked nuclear hyperchromasia set in a fibrillary collagenous background represents an important diagnostic feature of the sclerosing subtype.
Atypical lipomatous tumour / well-differentiated liposarcoma. In the inflammatory subtype, an abundant chronic inflammatory infiltrate may predominate. Scattered bizarre stromal cells are present.
Atypical lipomatous tumour / well-differentiated liposarcoma. If the inflammatory component predominates, the identification of hyperchromatic, atypical stromal cells represents the most useful diagnostic clue.
Atypical lipomatous tumour / well-differentiated liposarcoma. Genomic quantitative profile obtained by array comparative genomic hybridization. The profile is simple, showing the characteristic 12q14-q15 amplification including MDM2 (black arrow). Amplification of 1q23-q24 and 2q11-q13 is also observed in this case (blue arrows).
Atypical lipomatous tumour / well-differentiated liposarcoma. Interphase FISH using probes for MDM2 (green signal) and centromere of chromosome 12 (red signal) showing high-level amplification of MDM2 grouped in clusters.
Atypical lipomatous tumour / well-differentiated liposarcoma. RHG-banded near-diploid karyotype. The sole chromosomal anomaly is the presence of a supernumerary ring chromosome (arrow).

Q: In atypical spindle cell / pleomorphic lipomatous tumor, ancillary immunohistochemistry frequently demonstrates a characteristic loss of nuclear [...] expression in the neoplastic cells.
Atypical spindle cell / pleomorphic lipomatous tumour. Neoplastic cells lack expression of RB1, while non-neoplastic endothelial cells and macrophages show intact nuclear RB1 expression.
A: RB1
Back Extra: Atypical Spindle Cell / Pleomorphic Lipomatous Tumour
- Clinical: Atypical spindle cell / pleomorphic lipomatous tumour presents as a persistent or enlarging soft tissue mass, predominantly in middle-aged adults, with a peak incidence in the sixth decade of life.
- Micro: Microscopically, the tumour shows a wide range of appearances, from paucicellular with bland spindle cells to highly cellular with atypical hyperchromatic spindle cells, adipocytes, and lipoblasts.
- Ancillary: Ancillary studies show variable expression of CD34, S100, and desmin, loss of nuclear RB1 expression in about 50-70% of cases, and the absence of MDM2 or CDK4 amplification.
Reference Gallery:
Atypical spindle cell / pleomorphic lipomatous tumour. Moderately cellular example showing spindle cells irregularly admixed with adipocytic cells. The atypical spindle tumour cells show an ill-defined, pale eosinophilic cytoplasm with hyperchromatic nuclei, set in a collagenous and myxoid stroma.
Atypical spindle cell / pleomorphic lipomatous tumour. Cellular example composed of moderately atypical hyperchromatic spindle cells.
Atypical spindle cell / pleomorphic lipomatous tumour. Area composed of atypical hyperchromatic spindle cells, adipocytes, multinucleated (floret-like) cells, and a collagenous extracellular matrix.
Atypical spindle cell / pleomorphic lipomatous tumour. Bizarre pleomorphic cells and atypical spindle cells with enlarged, irregular, and hyperchromatic nuclei, irregularly admixed with lipoblasts.
Atypical spindle cell / pleomorphic lipomatous tumour. Neoplastic cells lack expression of RB1, while non-neoplastic endothelial cells and macrophages show intact nuclear RB1 expression.

Q: Microscopically, atypical spindle cell / pleomorphic lipomatous tumor typically features a collagenous or myxoid stroma containing atypical hyperchromatic spindle cells, adipocytes, lipoblasts, and distinctive multinucleated [...] cells.
Atypical spindle cell / pleomorphic lipomatous tumour. Moderately cellular example showing spindle cells irregularly admixed with adipocytic cells. The atypical spindle tumour cells show an ill-defined, pale eosinophilic cytoplasm with hyperchromatic nuclei, set in a collagenous and myxoid stroma.
Atypical spindle cell / pleomorphic lipomatous tumour. Area composed of atypical hyperchromatic spindle cells, adipocytes, multinucleated (floret-like) cells, and a collagenous extracellular matrix.
Atypical spindle cell / pleomorphic lipomatous tumour. Bizarre pleomorphic cells and atypical spindle cells with enlarged, irregular, and hyperchromatic nuclei, irregularly admixed with lipoblasts.
A: floret-like
Back Extra: Atypical Spindle Cell / Pleomorphic Lipomatous Tumour
- Clinical: Atypical spindle cell / pleomorphic lipomatous tumour presents as a persistent or enlarging soft tissue mass, predominantly in middle-aged adults, with a peak incidence in the sixth decade of life.
- Micro: Microscopically, the tumour shows a wide range of appearances, from paucicellular with bland spindle cells to highly cellular with atypical hyperchromatic spindle cells, adipocytes, and lipoblasts.
- Ancillary: Ancillary studies show variable expression of CD34, S100, and desmin, loss of nuclear RB1 expression in about 50-70% of cases, and the absence of MDM2 or CDK4 amplification.
Reference Gallery:
Atypical spindle cell / pleomorphic lipomatous tumour. Moderately cellular example showing spindle cells irregularly admixed with adipocytic cells. The atypical spindle tumour cells show an ill-defined, pale eosinophilic cytoplasm with hyperchromatic nuclei, set in a collagenous and myxoid stroma.
Atypical spindle cell / pleomorphic lipomatous tumour. Cellular example composed of moderately atypical hyperchromatic spindle cells.
Atypical spindle cell / pleomorphic lipomatous tumour. Area composed of atypical hyperchromatic spindle cells, adipocytes, multinucleated (floret-like) cells, and a collagenous extracellular matrix.
Atypical spindle cell / pleomorphic lipomatous tumour. Bizarre pleomorphic cells and atypical spindle cells with enlarged, irregular, and hyperchromatic nuclei, irregularly admixed with lipoblasts.
Atypical spindle cell / pleomorphic lipomatous tumour. Neoplastic cells lack expression of RB1, while non-neoplastic endothelial cells and macrophages show intact nuclear RB1 expression.

Q: Microscopic examination of Haemosiderotic fibrolipomatous tumour characteristically reveals lobules of mature fat intersected by fibrous septa containing bland spindle cells and prominent macrophages laden with [...].
Haemosiderotic fibrolipomatous tumour. Low-magnification view of haemosiderotic fibrolipomatous tumour, containing mature adipose tissue and fibrous septa with spindled cells and macrophages containing conspicuous haemosiderin.
Haemosiderotic fibrolipomatous tumour. Collections of haemosiderin-laden macrophages are observed admixed with the bland spindle cells; mitotic activity is low and necrosis is absent.
A: hemosiderin
Back Extra: Haemosiderotic fibrolipomatous tumour
- Clinical: HFLT is a slow-growing, sometimes painful subcutaneous mass common in the foot, especially in females in their fifth and sixth decades of life.
- Micro: HFLT consists of lobules of mature fat, fibroblastic spindle cells containing haemosiderin, and haemosiderin-laden macrophages.
- Ancillary: Cytogenetic analysis often shows a t(1;10)(p22-p31;q24-q25) translocation, targeting TGFBR3 and OGA.
Reference Gallery:
Haemosiderotic fibrolipomatous tumour. Low-magnification view of haemosiderotic fibrolipomatous tumour, containing mature adipose tissue and fibrous septa with spindled cells and macrophages containing conspicuous haemosiderin.
Haemosiderotic fibrolipomatous tumour. Perivascular collections of bland spindle cells and osteoclast-like giant cells. Note also haemosiderin in some spindle cells.
Haemosiderotic fibrolipomatous tumour. Collections of haemosiderin-laden macrophages are observed admixed with the bland spindle cells; mitotic activity is low and necrosis is absent.
Haemosiderotic fibrolipomatous tumour. The spindle cells can be present between individual adipocytes.
Haemosiderotic fibrolipomatous tumour. Sagittal view of fat-saturated T1-weighted fast spin echo MRI sequences of the foot shows a heterogeneous, predominantly fatty subcutaneous soft tissue mass (arrow). The mass abuts but does not invade the dorsal neurovascular structures and extensor tendons.

Q: Haemosiderotic fibrolipomatous tumour typically presents as a slow-growing, predominantly fatty subcutaneous mass that is most commonly located in the [...] of middle-aged adult females.
Haemosiderotic fibrolipomatous tumour. Sagittal view of fat-saturated T1-weighted fast spin echo MRI sequences of the foot shows a heterogeneous, predominantly fatty subcutaneous soft tissue mass (arrow). The mass abuts but does not invade the dorsal neurovascular structures and extensor tendons.
A: foot
Back Extra: Haemosiderotic fibrolipomatous tumour
- Clinical: HFLT is a slow-growing, sometimes painful subcutaneous mass common in the foot, especially in females in their fifth and sixth decades of life.
- Micro: HFLT consists of lobules of mature fat, fibroblastic spindle cells containing haemosiderin, and haemosiderin-laden macrophages.
- Ancillary: Cytogenetic analysis often shows a t(1;10)(p22-p31;q24-q25) translocation, targeting TGFBR3 and OGA.
Reference Gallery:
Haemosiderotic fibrolipomatous tumour. Low-magnification view of haemosiderotic fibrolipomatous tumour, containing mature adipose tissue and fibrous septa with spindled cells and macrophages containing conspicuous haemosiderin.
Haemosiderotic fibrolipomatous tumour. Perivascular collections of bland spindle cells and osteoclast-like giant cells. Note also haemosiderin in some spindle cells.
Haemosiderotic fibrolipomatous tumour. Collections of haemosiderin-laden macrophages are observed admixed with the bland spindle cells; mitotic activity is low and necrosis is absent.
Haemosiderotic fibrolipomatous tumour. The spindle cells can be present between individual adipocytes.
Haemosiderotic fibrolipomatous tumour. Sagittal view of fat-saturated T1-weighted fast spin echo MRI sequences of the foot shows a heterogeneous, predominantly fatty subcutaneous soft tissue mass (arrow). The mass abuts but does not invade the dorsal neurovascular structures and extensor tendons.

Q: The histological hallmark of dedifferentiated liposarcoma is the [...] from a well-differentiated liposarcoma to a non-lipogenic sarcoma of variable grade.
Dedifferentiated liposarcoma. Abrupt transition from well-differentiated liposarcoma to high-grade non-lipogenic pleomorphic sarcoma is seen.
A: abrupt transition
Back Extra: Dedifferentiated Liposarcoma
- Clinical: Dedifferentiated Liposarcoma often presents as a large, painless mass, particularly in the retroperitoneum, and may show recent increase in size in the limbs.
- Micro: The histological hallmark of Dedifferentiated Liposarcoma is the abrupt transition from well-differentiated liposarcoma to a non-lipogenic sarcoma of variable grade.
- Ancillary: Detection of MDM2 amplification by FISH is a key ancillary test to distinguish Dedifferentiated Liposarcoma from other undifferentiated sarcomas.
Reference Gallery:
Dedifferentiated liposarcoma. Multivisceral resection gross specimen featuring a large lipomatous mass associated with solid nodules representing the dedifferentiated component.
Dedifferentiated liposarcoma. Abrupt transition from well-differentiated liposarcoma to high-grade non-lipogenic pleomorphic sarcoma is seen.
Dedifferentiated liposarcoma. The morphology of the dedifferentiated component most often overlaps with that of undifferentiated pleomorphic sarcoma.
Dedifferentiated liposarcoma. The morphology of the dedifferentiated component may be identical to that of myxofibrosarcoma.
Dedifferentiated liposarcoma. Low-grade dedifferentiation is characterized most often by the presence of uniform fibroblastic spindle cells with mild nuclear atypia.
Dedifferentiated liposarcoma. Rhabdomyoblastic differentiation represents the most common type of heterologous differentiation in dedifferentiated liposarcoma.
Dedifferentiated liposarcoma. Rarely, dedifferentiated liposarcoma may feature a distinctive whorled pattern reminiscent of neural or meningothelial structures.
Dedifferentiated liposarcoma. Rarely, the dedifferentiated component exhibits striking lipogenic differentiation.
Dedifferentiated liposarcoma. Diffuse nuclear expression of MDM2 is consistently observed in dedifferentiated liposarcoma.
Dedifferentiated liposarcoma. Array comparative genomic hybridization. Relatively simple quantitative genomic profile, showing characteristic high-level 12q amplification (black arrow) including MDM2 (12q15). The 12q amplicon is large (from 12q12 up to q21) and discontinuous. It contains several genes frequently coamplified with MDM2, such as CDK4, HMGA2, and FRS2. A few other imbalanced alterations are also observed: amplification of 1q24, 2p11, 2q11, and 6p11-q16 regions (blue arrows), as well as gains and losses on chromosomes 1, 16, and 20.

Q: A key diagnostic finding in dedifferentiated liposarcoma is the diffuse nuclear overexpression and high-level gene amplification of [...], which distinguishes it from other undifferentiated sarcomas.
Dedifferentiated liposarcoma. Diffuse nuclear expression of MDM2 is consistently observed in dedifferentiated liposarcoma.
Dedifferentiated liposarcoma. Array comparative genomic hybridization. Relatively simple quantitative genomic profile, showing characteristic high-level 12q amplification (black arrow) including MDM2 (12q15). The 12q amplicon is large (from 12q12 up to q21) and discontinuous. It contains several genes frequently coamplified with MDM2, such as CDK4, HMGA2, and FRS2. A few other imbalanced alterations are also observed: amplification of 1q24, 2p11, 2q11, and 6p11-q16 regions (blue arrows), as well as gains and losses on chromosomes 1, 16, and 20.
A: MDM2
Back Extra: Dedifferentiated Liposarcoma
- Clinical: Dedifferentiated Liposarcoma often presents as a large, painless mass, particularly in the retroperitoneum, and may show recent increase in size in the limbs.
- Micro: The histological hallmark of Dedifferentiated Liposarcoma is the abrupt transition from well-differentiated liposarcoma to a non-lipogenic sarcoma of variable grade.
- Ancillary: Detection of MDM2 amplification by FISH is a key ancillary test to distinguish Dedifferentiated Liposarcoma from other undifferentiated sarcomas.
Reference Gallery:
Dedifferentiated liposarcoma. Multivisceral resection gross specimen featuring a large lipomatous mass associated with solid nodules representing the dedifferentiated component.
Dedifferentiated liposarcoma. Abrupt transition from well-differentiated liposarcoma to high-grade non-lipogenic pleomorphic sarcoma is seen.
Dedifferentiated liposarcoma. The morphology of the dedifferentiated component most often overlaps with that of undifferentiated pleomorphic sarcoma.
Dedifferentiated liposarcoma. The morphology of the dedifferentiated component may be identical to that of myxofibrosarcoma.
Dedifferentiated liposarcoma. Low-grade dedifferentiation is characterized most often by the presence of uniform fibroblastic spindle cells with mild nuclear atypia.
Dedifferentiated liposarcoma. Rhabdomyoblastic differentiation represents the most common type of heterologous differentiation in dedifferentiated liposarcoma.
Dedifferentiated liposarcoma. Rarely, dedifferentiated liposarcoma may feature a distinctive whorled pattern reminiscent of neural or meningothelial structures.
Dedifferentiated liposarcoma. Rarely, the dedifferentiated component exhibits striking lipogenic differentiation.
Dedifferentiated liposarcoma. Diffuse nuclear expression of MDM2 is consistently observed in dedifferentiated liposarcoma.
Dedifferentiated liposarcoma. Array comparative genomic hybridization. Relatively simple quantitative genomic profile, showing characteristic high-level 12q amplification (black arrow) including MDM2 (12q15). The 12q amplicon is large (from 12q12 up to q21) and discontinuous. It contains several genes frequently coamplified with MDM2, such as CDK4, HMGA2, and FRS2. A few other imbalanced alterations are also observed: amplification of 1q24, 2p11, 2q11, and 6p11-q16 regions (blue arrows), as well as gains and losses on chromosomes 1, 16, and 20.

Q: Grossly and clinically, dedifferentiated liposarcoma often presents as a large, painless mass with solid nodules that most frequently arises in the deep tissues of the [...].
Dedifferentiated liposarcoma. Multivisceral resection gross specimen featuring a large lipomatous mass associated with solid nodules representing the dedifferentiated component.
A: retroperitoneum
Back Extra: Dedifferentiated Liposarcoma
- Clinical: Dedifferentiated Liposarcoma often presents as a large, painless mass, particularly in the retroperitoneum, and may show recent increase in size in the limbs.
- Micro: The histological hallmark of Dedifferentiated Liposarcoma is the abrupt transition from well-differentiated liposarcoma to a non-lipogenic sarcoma of variable grade.
- Ancillary: Detection of MDM2 amplification by FISH is a key ancillary test to distinguish Dedifferentiated Liposarcoma from other undifferentiated sarcomas.
Reference Gallery:
Dedifferentiated liposarcoma. Multivisceral resection gross specimen featuring a large lipomatous mass associated with solid nodules representing the dedifferentiated component.
Dedifferentiated liposarcoma. Abrupt transition from well-differentiated liposarcoma to high-grade non-lipogenic pleomorphic sarcoma is seen.
Dedifferentiated liposarcoma. The morphology of the dedifferentiated component most often overlaps with that of undifferentiated pleomorphic sarcoma.
Dedifferentiated liposarcoma. The morphology of the dedifferentiated component may be identical to that of myxofibrosarcoma.
Dedifferentiated liposarcoma. Low-grade dedifferentiation is characterized most often by the presence of uniform fibroblastic spindle cells with mild nuclear atypia.
Dedifferentiated liposarcoma. Rhabdomyoblastic differentiation represents the most common type of heterologous differentiation in dedifferentiated liposarcoma.
Dedifferentiated liposarcoma. Rarely, dedifferentiated liposarcoma may feature a distinctive whorled pattern reminiscent of neural or meningothelial structures.
Dedifferentiated liposarcoma. Rarely, the dedifferentiated component exhibits striking lipogenic differentiation.
Dedifferentiated liposarcoma. Diffuse nuclear expression of MDM2 is consistently observed in dedifferentiated liposarcoma.
Dedifferentiated liposarcoma. Array comparative genomic hybridization. Relatively simple quantitative genomic profile, showing characteristic high-level 12q amplification (black arrow) including MDM2 (12q15). The 12q amplicon is large (from 12q12 up to q21) and discontinuous. It contains several genes frequently coamplified with MDM2, such as CDK4, HMGA2, and FRS2. A few other imbalanced alterations are also observed: amplification of 1q24, 2p11, 2q11, and 6p11-q16 regions (blue arrows), as well as gains and losses on chromosomes 1, 16, and 20.

Q: Microscopically, low-grade Myxoid Liposarcoma features uniform, small round to ovoid cells within an abundant myxoid stroma, accompanied by a characteristic elaborate, branching [...].
Myxoid liposarcoma. Low-grade myxoid liposarcoma, with abundant myxoid matrix, and lymphangioma-like cystic spaces.
Myxoid liposarcoma. Higher-power magnification of low-grade myxoid liposarcoma, illustrating the characteristic elaborate capillary vasculature of this tumour. The neoplastic cells are small, round to ovoid, and bland. Lipoblasts were very difficult to find in this particular tumour and are not required for diagnosis.
A: capillary network
Back Extra: Myxoid Liposarcoma
- Clinical: Myxoid Liposarcoma typically presents as large, painless masses within the deep soft tissues of the extremities, most often the thigh.
- Micro: Characteristic features include uniform small, round to ovoid cells with a myxoid stroma and a delicate, branching capillary network.
- Ancillary: Demonstration of DDIT3 rearrangement (FUS-DDIT3 or EWSR1-DDIT3 fusion genes) is essential for confirming the diagnosis.
Reference Gallery:
Myxoid liposarcoma. Macroscopically, the tumour, present here within subcutaneous fat, has a soft, glistening reddish cut surface, due to old and recent haemorrhage.
Myxoid liposarcoma. Low-grade myxoid liposarcoma, with abundant myxoid matrix, and lymphangioma-like cystic spaces.
Myxoid liposarcoma. Higher-power magnification of low-grade myxoid liposarcoma, illustrating the characteristic elaborate capillary vasculature of this tumour. The neoplastic cells are small, round to ovoid, and bland. Lipoblasts were very difficult to find in this particular tumour and are not required for diagnosis.
Myxoidliposarcoma. Differentiating myxoid liposarcoma, with a component of mature white fat. On occasion, myxoid liposarcomas may contain abundant mature fat, mimicking lipoma with myxoid change.
Myxoid liposarcoma. Myxoid liposarcomas typically show increased cellularity at the periphery of lobules. This should not be interpreted as round cell change, for purposes of grading.
High-grade myxoid liposarcoma. This lesion shows an abrupt transition between typical low-grade histology (bottom) and high-grade, round cell morphology (top).
High-grade myxoid liposarcoma. High-power view showing cellular overlap, elevated nuclear grade, mitotic activity, and obscuring of the underlying vascular pattern.
Metastatic myxoid liposarcoma. This lesion is a metastasis from the surface of the spleen. Essentially all intra-abdominal and retroperitoneal myxoid liposarcomas represent metastases.
Myxoid liposarcoma. A Schematic illustration of the breakpoints involved in the translocations t(12;16)(q13.3;p11.2) and t(12;22)(q13.3;q12.2) resulting in FUS-DDIT3 and EWSR1-DDIT3 fusions, respectively. B The N-terminal transcriptional activation domain of FUS or EWSR1 is retained in the fusion to the entire coding region of DDIT3, which encodes an apparent DNA-binding and dimerization domain. There are at least 11 different isoforms of the FUS-DDIT3 fusion transcript (with types 1–3 being most common) and 4 of EWSR1-DDIT3 (with type 1 being most common in this rare molecular subtype).

Q: The diagnosis of Myxoid Liposarcoma is often confirmed by demonstrating a characteristic chromosomal rearrangement involving the [...] gene, typically resulting in a fusion with FUS or EWSR1.
Myxoid liposarcoma. A Schematic illustration of the breakpoints involved in the translocations t(12;16)(q13.3;p11.2) and t(12;22)(q13.3;q12.2) resulting in FUS-DDIT3 and EWSR1-DDIT3 fusions, respectively. B The N-terminal transcriptional activation domain of FUS or EWSR1 is retained in the fusion to the entire coding region of DDIT3, which encodes an apparent DNA-binding and dimerization domain. There are at least 11 different isoforms of the FUS-DDIT3 fusion transcript (with types 1–3 being most common) and 4 of EWSR1-DDIT3 (with type 1 being most common in this rare molecular subtype).
A: DDIT3
Back Extra: Myxoid Liposarcoma
- Clinical: Myxoid Liposarcoma typically presents as large, painless masses within the deep soft tissues of the extremities, most often the thigh.
- Micro: Characteristic features include uniform small, round to ovoid cells with a myxoid stroma and a delicate, branching capillary network.
- Ancillary: Demonstration of DDIT3 rearrangement (FUS-DDIT3 or EWSR1-DDIT3 fusion genes) is essential for confirming the diagnosis.
Reference Gallery:
Myxoid liposarcoma. Macroscopically, the tumour, present here within subcutaneous fat, has a soft, glistening reddish cut surface, due to old and recent haemorrhage.
Myxoid liposarcoma. Low-grade myxoid liposarcoma, with abundant myxoid matrix, and lymphangioma-like cystic spaces.
Myxoid liposarcoma. Higher-power magnification of low-grade myxoid liposarcoma, illustrating the characteristic elaborate capillary vasculature of this tumour. The neoplastic cells are small, round to ovoid, and bland. Lipoblasts were very difficult to find in this particular tumour and are not required for diagnosis.
Myxoidliposarcoma. Differentiating myxoid liposarcoma, with a component of mature white fat. On occasion, myxoid liposarcomas may contain abundant mature fat, mimicking lipoma with myxoid change.
Myxoid liposarcoma. Myxoid liposarcomas typically show increased cellularity at the periphery of lobules. This should not be interpreted as round cell change, for purposes of grading.
High-grade myxoid liposarcoma. This lesion shows an abrupt transition between typical low-grade histology (bottom) and high-grade, round cell morphology (top).
High-grade myxoid liposarcoma. High-power view showing cellular overlap, elevated nuclear grade, mitotic activity, and obscuring of the underlying vascular pattern.
Metastatic myxoid liposarcoma. This lesion is a metastasis from the surface of the spleen. Essentially all intra-abdominal and retroperitoneal myxoid liposarcomas represent metastases.
Myxoid liposarcoma. A Schematic illustration of the breakpoints involved in the translocations t(12;16)(q13.3;p11.2) and t(12;22)(q13.3;q12.2) resulting in FUS-DDIT3 and EWSR1-DDIT3 fusions, respectively. B The N-terminal transcriptional activation domain of FUS or EWSR1 is retained in the fusion to the entire coding region of DDIT3, which encodes an apparent DNA-binding and dimerization domain. There are at least 11 different isoforms of the FUS-DDIT3 fusion transcript (with types 1–3 being most common) and 4 of EWSR1-DDIT3 (with type 1 being most common in this rare molecular subtype).

Q: In Myxoid Liposarcoma, the progression to a high-grade tumor is histologically defined by an abrupt transition to a hypercellular [...] component that typically obscures the underlying vascular pattern.
High-grade myxoid liposarcoma. This lesion shows an abrupt transition between typical low-grade histology (bottom) and high-grade, round cell morphology (top).
High-grade myxoid liposarcoma. High-power view showing cellular overlap, elevated nuclear grade, mitotic activity, and obscuring of the underlying vascular pattern.
A: round cell
Back Extra: Myxoid Liposarcoma
- Clinical: Myxoid Liposarcoma typically presents as large, painless masses within the deep soft tissues of the extremities, most often the thigh.
- Micro: Characteristic features include uniform small, round to ovoid cells with a myxoid stroma and a delicate, branching capillary network.
- Ancillary: Demonstration of DDIT3 rearrangement (FUS-DDIT3 or EWSR1-DDIT3 fusion genes) is essential for confirming the diagnosis.
Reference Gallery:
Myxoid liposarcoma. Macroscopically, the tumour, present here within subcutaneous fat, has a soft, glistening reddish cut surface, due to old and recent haemorrhage.
Myxoid liposarcoma. Low-grade myxoid liposarcoma, with abundant myxoid matrix, and lymphangioma-like cystic spaces.
Myxoid liposarcoma. Higher-power magnification of low-grade myxoid liposarcoma, illustrating the characteristic elaborate capillary vasculature of this tumour. The neoplastic cells are small, round to ovoid, and bland. Lipoblasts were very difficult to find in this particular tumour and are not required for diagnosis.
Myxoidliposarcoma. Differentiating myxoid liposarcoma, with a component of mature white fat. On occasion, myxoid liposarcomas may contain abundant mature fat, mimicking lipoma with myxoid change.
Myxoid liposarcoma. Myxoid liposarcomas typically show increased cellularity at the periphery of lobules. This should not be interpreted as round cell change, for purposes of grading.
High-grade myxoid liposarcoma. This lesion shows an abrupt transition between typical low-grade histology (bottom) and high-grade, round cell morphology (top).
High-grade myxoid liposarcoma. High-power view showing cellular overlap, elevated nuclear grade, mitotic activity, and obscuring of the underlying vascular pattern.
Metastatic myxoid liposarcoma. This lesion is a metastasis from the surface of the spleen. Essentially all intra-abdominal and retroperitoneal myxoid liposarcomas represent metastases.
Myxoid liposarcoma. A Schematic illustration of the breakpoints involved in the translocations t(12;16)(q13.3;p11.2) and t(12;22)(q13.3;q12.2) resulting in FUS-DDIT3 and EWSR1-DDIT3 fusions, respectively. B The N-terminal transcriptional activation domain of FUS or EWSR1 is retained in the fusion to the entire coding region of DDIT3, which encodes an apparent DNA-binding and dimerization domain. There are at least 11 different isoforms of the FUS-DDIT3 fusion transcript (with types 1–3 being most common) and 4 of EWSR1-DDIT3 (with type 1 being most common in this rare molecular subtype).

Q: A diagnostic histologic hallmark of Myxoid Pleomorphic Liposarcoma is the mixture of conventional myxoid liposarcoma-like areas with high-grade cellular zones containing marked nuclear atypia and [...].
Myxoid pleomorphic liposarcoma. A fibrous, densely cellular area with pleomorphism is adjacent to a myxoid liposarcoma–like component.
Myxoid pleomorphic liposarcoma. Myxoid pleomorphic liposarcoma showing a myxoid liposarcoma–like arborizing capillary vasculature, marked nuclear atypia, and pleomorphic lipoblasts.
A: pleomorphic lipoblasts
Back Extra: Myxoid Pleomorphic Liposarcoma
- Clinical: Myxoid pleomorphic liposarcoma generally manifests as a large, deep-seated soft tissue mass in children and young adults, with a female predominance.
- Micro: Histologically, the tumour shows a mix of myxoid liposarcoma–like areas with abundant myxoid matrix and pleomorphic spindle or ovoid cells with hyperchromatic nuclei in more cellular, high-grade areas.
- Ancillary: Myxoid pleomorphic liposarcoma lacks the FUS/EWSR1-DDIT3 gene fusions seen in conventional myxoid liposarcoma and the MDM2 amplification present in well-differentiated/dedifferentiated liposarcoma.
Reference Gallery:
Myxoid pleomorphic liposarcoma. A fibrous, densely cellular area with pleomorphism is adjacent to a myxoid liposarcoma–like component.
Myxoid pleomorphic liposarcoma. Pseudocystic changes in myxoid areas with associated classic monovacuolated and multivacuolated lipoblasts. An isolated pleomorphic cell is seen.
Myxoid pleomorphic liposarcoma. Delicate vaguely plexiform vascular pattern in the context of a myxoid background. Primitive cells and isolated cells with a hyperchromatic nucleus are seen.
Myxoid pleomorphic liposarcoma. Myxoid pleomorphic liposarcoma showing a myxoid liposarcoma–like arborizing capillary vasculature, marked nuclear atypia, and pleomorphic lipoblasts.

Q: Molecularly, Myxoid Pleomorphic Liposarcoma is distinguished from conventional myxoid liposarcoma by the lack of the characteristic [...] gene fusions (it also lacks MDM2 amplification).
Myxoid pleomorphic liposarcoma. A fibrous, densely cellular area with pleomorphism is adjacent to a myxoid liposarcoma–like component.
Myxoid pleomorphic liposarcoma. Delicate vaguely plexiform vascular pattern in the context of a myxoid background. Primitive cells and isolated cells with a hyperchromatic nucleus are seen.
A: FUS/EWSR1-DDIT3
Back Extra: Myxoid Pleomorphic Liposarcoma
- Clinical: Myxoid pleomorphic liposarcoma generally manifests as a large, deep-seated soft tissue mass in children and young adults, with a female predominance.
- Micro: Histologically, the tumour shows a mix of myxoid liposarcoma–like areas with abundant myxoid matrix and pleomorphic spindle or ovoid cells with hyperchromatic nuclei in more cellular, high-grade areas.
- Ancillary: Myxoid pleomorphic liposarcoma lacks the FUS/EWSR1-DDIT3 gene fusions seen in conventional myxoid liposarcoma and the MDM2 amplification present in well-differentiated/dedifferentiated liposarcoma.
Reference Gallery:
Myxoid pleomorphic liposarcoma. A fibrous, densely cellular area with pleomorphism is adjacent to a myxoid liposarcoma–like component.
Myxoid pleomorphic liposarcoma. Pseudocystic changes in myxoid areas with associated classic monovacuolated and multivacuolated lipoblasts. An isolated pleomorphic cell is seen.
Myxoid pleomorphic liposarcoma. Delicate vaguely plexiform vascular pattern in the context of a myxoid background. Primitive cells and isolated cells with a hyperchromatic nucleus are seen.
Myxoid pleomorphic liposarcoma. Myxoid pleomorphic liposarcoma showing a myxoid liposarcoma–like arborizing capillary vasculature, marked nuclear atypia, and pleomorphic lipoblasts.

Q: The diagnosis of Pleomorphic Liposarcoma requires the histologic identification of [...] within a background of high-grade, undifferentiated sarcoma.
Pleomorphic liposarcoma. Note that most of the lesion shows spindle cells and such foci cannot be diagnosed as pleomorphic liposarcoma. Pleomorphic liposarcoma is diagnosed on H&E staining by identifying pleomorphic lipoblasts, as in the upper left of the image, in which lipid droplets crisply indent the pleomorphic nucleus. Sometimes examination of multiple tissue blocks is required to identify the diagnostic areas, which can be missed on needle biopsies.
Pleomorphic liposarcoma. This field shows numerous pleomorphic lipoblasts, each with nuclear indentations by cytoplasmic lipid droplets.
A: pleomorphic lipoblasts
Back Extra: Pleomorphic Liposarcoma
- Clinical: Most patients report a rapidly growing painless mass, usually with a short preoperative duration (3–6 months). It is rare, accounting for < 5% of all liposarcomas, and is more common in adults over 50, with a slight male predominance.
- Micro: Histologically, the tumour contains a varying proportion of pleomorphic lipoblasts in a background of a high-grade, usually pleomorphic, undifferentiated sarcoma. The presence of lipoblasts is necessary for diagnosis.
- Ancillary: No pathognomonic structural rearrangement has been identified. The most frequent mutations involve TP53 and NF1. Metaphase cells show high chromosomal counts and complex structural rearrangements.
Reference Gallery:
Pleomorphic liposarcoma. Note that most of the lesion shows spindle cells and such foci cannot be diagnosed as pleomorphic liposarcoma. Pleomorphic liposarcoma is diagnosed on H&E staining by identifying pleomorphic lipoblasts, as in the upper left of the image, in which lipid droplets crisply indent the pleomorphic nucleus. Sometimes examination of multiple tissue blocks is required to identify the diagnostic areas, which can be missed on needle biopsies.
Pleomorphic liposarcoma. This field shows numerous pleomorphic lipoblasts, each with nuclear indentations by cytoplasmic lipid droplets.
Pleomorphic liposarcoma. These neoplasms feature some of the most bizarre nuclei in human neoplasia and lack characteristic translocations and gene fusions.
Pleomorphic liposarcoma. Metaphase cell (RHG-banding) showing numerous quantitative and structural chromosomal alterations: near-tetraploidy and complex marker chromosomes.
Pleomorphic liposarcoma. This epithelioid pleomorphic liposarcoma shows lipid droplets but also shows many epithelioid cells with round nuclei and a rich vascular network.

Q: Unlike myxoid or well-differentiated variants, Pleomorphic Liposarcoma lacks pathognomonic structural rearrangements and instead features a [...] with frequent mutations in TP53 and NF1.
Pleomorphic liposarcoma. Metaphase cell (RHG-banding) showing numerous quantitative and structural chromosomal alterations: near-tetraploidy and complex marker chromosomes.
A: complex karyotype
Back Extra: Pleomorphic Liposarcoma
- Clinical: Most patients report a rapidly growing painless mass, usually with a short preoperative duration (3–6 months). It is rare, accounting for < 5% of all liposarcomas, and is more common in adults over 50, with a slight male predominance.
- Micro: Histologically, the tumour contains a varying proportion of pleomorphic lipoblasts in a background of a high-grade, usually pleomorphic, undifferentiated sarcoma. The presence of lipoblasts is necessary for diagnosis.
- Ancillary: No pathognomonic structural rearrangement has been identified. The most frequent mutations involve TP53 and NF1. Metaphase cells show high chromosomal counts and complex structural rearrangements.
Reference Gallery:
Pleomorphic liposarcoma. Note that most of the lesion shows spindle cells and such foci cannot be diagnosed as pleomorphic liposarcoma. Pleomorphic liposarcoma is diagnosed on H&E staining by identifying pleomorphic lipoblasts, as in the upper left of the image, in which lipid droplets crisply indent the pleomorphic nucleus. Sometimes examination of multiple tissue blocks is required to identify the diagnostic areas, which can be missed on needle biopsies.
Pleomorphic liposarcoma. This field shows numerous pleomorphic lipoblasts, each with nuclear indentations by cytoplasmic lipid droplets.
Pleomorphic liposarcoma. These neoplasms feature some of the most bizarre nuclei in human neoplasia and lack characteristic translocations and gene fusions.
Pleomorphic liposarcoma. Metaphase cell (RHG-banding) showing numerous quantitative and structural chromosomal alterations: near-tetraploidy and complex marker chromosomes.
Pleomorphic liposarcoma. This epithelioid pleomorphic liposarcoma shows lipid droplets but also shows many epithelioid cells with round nuclei and a rich vascular network.

Q: In the spectrum of Ectopic Meningioma and Meningothelial Hamartoma, the hamartomatous lesions often present as incidental scalp masses in neonates featuring slit-like spaces and lamellated calcifications known as [...].
Meningothelial hamartoma of the scalp. Occipital scalp mass resected from a neonate. The lesion involves the dermis and subcutaneous soft tissue. Note the slit-like spaces mimicking subarachnoid spaces, in association with occasional more easily recognizable meningothelial clusters and psammoma bodies.
A: psammoma bodies
Back Extra: Ectopic Meningioma and Meningothelial Hamartoma
- Clinical: Ectopic meningiomas present as painless, slow-growing masses, while meningothelial hamartomas are often detected as incidental scalp masses in neonates.
- Micro: Ectopic meningiomas show a range of histological appearances similar to intracranial meningiomas, and meningothelial hamartomas often present with slit-like spaces lined by meningothelial cells and psammoma bodies.
- Ancillary: Immunohistochemistry shows coexpression of vimentin, EMA, and progesterone receptors, and SSTR2A can be expressed in pulmonary meningothelial-like nodules.
Reference Gallery:
Ectopic (meningothelial) meningioma. This epidural tumour surrounded and tracked along a paraspinal nerve root. Invasion of adjacent skeletal muscle was seen in other sections.
Meningothelial hamartoma of the scalp. Occipital scalp mass resected from a neonate. The lesion involves the dermis and subcutaneous soft tissue. Note the slit-like spaces mimicking subarachnoid spaces, in association with occasional more easily recognizable meningothelial clusters and psammoma bodies.
Meningothelial rest. This ectopic rest was an incidental microscopic finding within a lymph node.

Q: When discussing Ectopic Meningioma and Meningothelial Hamartoma, an ectopic meningioma may present as an epidural tumor that surrounds and tracks along paraspinal [...].
Ectopic (meningothelial) meningioma. This epidural tumour surrounded and tracked along a paraspinal nerve root. Invasion of adjacent skeletal muscle was seen in other sections.
A: nerve roots
Back Extra: Ectopic Meningioma and Meningothelial Hamartoma
- Clinical: Ectopic meningiomas present as painless, slow-growing masses, while meningothelial hamartomas are often detected as incidental scalp masses in neonates.
- Micro: Ectopic meningiomas show a range of histological appearances similar to intracranial meningiomas, and meningothelial hamartomas often present with slit-like spaces lined by meningothelial cells and psammoma bodies.
- Ancillary: Immunohistochemistry shows coexpression of vimentin, EMA, and progesterone receptors, and SSTR2A can be expressed in pulmonary meningothelial-like nodules.
Reference Gallery:
Ectopic (meningothelial) meningioma. This epidural tumour surrounded and tracked along a paraspinal nerve root. Invasion of adjacent skeletal muscle was seen in other sections.
Meningothelial hamartoma of the scalp. Occipital scalp mass resected from a neonate. The lesion involves the dermis and subcutaneous soft tissue. Note the slit-like spaces mimicking subarachnoid spaces, in association with occasional more easily recognizable meningothelial clusters and psammoma bodies.
Meningothelial rest. This ectopic rest was an incidental microscopic finding within a lymph node.

Q: As a related finding to Ectopic Meningioma and Meningothelial Hamartoma, ectopic meningothelial tissue can sometimes be identified as an incidental microscopic finding within a lymph node, referred to as a meningothelial [...].
Meningothelial rest. This ectopic rest was an incidental microscopic finding within a lymph node.
A: rest
Back Extra: Ectopic Meningioma and Meningothelial Hamartoma
- Clinical: Ectopic meningiomas present as painless, slow-growing masses, while meningothelial hamartomas are often detected as incidental scalp masses in neonates.
- Micro: Ectopic meningiomas show a range of histological appearances similar to intracranial meningiomas, and meningothelial hamartomas often present with slit-like spaces lined by meningothelial cells and psammoma bodies.
- Ancillary: Immunohistochemistry shows coexpression of vimentin, EMA, and progesterone receptors, and SSTR2A can be expressed in pulmonary meningothelial-like nodules.
Reference Gallery:
Ectopic (meningothelial) meningioma. This epidural tumour surrounded and tracked along a paraspinal nerve root. Invasion of adjacent skeletal muscle was seen in other sections.
Meningothelial hamartoma of the scalp. Occipital scalp mass resected from a neonate. The lesion involves the dermis and subcutaneous soft tissue. Note the slit-like spaces mimicking subarachnoid spaces, in association with occasional more easily recognizable meningothelial clusters and psammoma bodies.
Meningothelial rest. This ectopic rest was an incidental microscopic finding within a lymph node.

Q: Histologically, Fibrous Hamartoma of Infancy is characterized by a pathognomonic [...] organoid pattern consisting of fascicles of bland fibroblastic cells, mature adipose tissue, and myxoid nodules containing primitive mesenchymal cells.
Fibrous hamartoma of infancy. Low-power view showing the triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view showing the triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
A: triphasic
Back Extra: Fibrous Hamartoma of Infancy
- Clinical: Fibrous hamartoma of infancy typically presents as painless solitary subcutaneous masses, sometimes with overlying skin discolouration, oedema, hypertrichosis, and tethering. About 15–25% of cases are congenital.
- Micro: The lesion has a triphasic organoid pattern with haphazardly arranged fascicles of cytologically bland fibroblastic/myofibroblastic cells, mature adipose tissue, and myxoid nodules containing primitive mesenchymal cells.
- Ancillary: Immunohistochemistry shows variable expression of SMA in the fibroblastic areas and CD34 in the primitive mesenchyme and areas with giant cell fibroblastoma–like morphology.
Reference Gallery:
Fibrous hamartoma of infancy. Low-power view showing the triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view showing the triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Giant cell fibroblastoma–like areas with abundant collagen with cracking artefact forming slit-like spaces lined by flattened tumour cells.
Fibrous hamartoma of infancy with sarcomatous features. Typical triphasic fibrous hamartoma of infancy showing an abrupt transition to a highly cellular, sarcomatous spindle cell neoplasm.
Fibrous hamartoma of infancy with sarcomatous features. High-power view of the sarcomatous area showing spindled to round cells with hyperchromatic nuclei and brisk mitotic activity.

Q: Some cases of Fibrous Hamartoma of Infancy feature areas with abundant collagen and a cracking artifact that forms slit-like spaces lined by flattened tumor cells, which is known as a [...]-like morphology.
Fibrous hamartoma of infancy. Giant cell fibroblastoma–like areas with abundant collagen with cracking artefact forming slit-like spaces lined by flattened tumour cells.
A: giant cell fibroblastoma
Back Extra: Fibrous Hamartoma of Infancy
- Clinical: Fibrous hamartoma of infancy typically presents as painless solitary subcutaneous masses, sometimes with overlying skin discolouration, oedema, hypertrichosis, and tethering. About 15–25% of cases are congenital.
- Micro: The lesion has a triphasic organoid pattern with haphazardly arranged fascicles of cytologically bland fibroblastic/myofibroblastic cells, mature adipose tissue, and myxoid nodules containing primitive mesenchymal cells.
- Ancillary: Immunohistochemistry shows variable expression of SMA in the fibroblastic areas and CD34 in the primitive mesenchyme and areas with giant cell fibroblastoma–like morphology.
Reference Gallery:
Fibrous hamartoma of infancy. Low-power view showing the triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view showing the triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Giant cell fibroblastoma–like areas with abundant collagen with cracking artefact forming slit-like spaces lined by flattened tumour cells.
Fibrous hamartoma of infancy with sarcomatous features. Typical triphasic fibrous hamartoma of infancy showing an abrupt transition to a highly cellular, sarcomatous spindle cell neoplasm.
Fibrous hamartoma of infancy with sarcomatous features. High-power view of the sarcomatous area showing spindled to round cells with hyperchromatic nuclei and brisk mitotic activity.

Q: Although typically a benign lesion, Fibrous Hamartoma of Infancy can rarely exhibit an abrupt transition to a highly cellular spindle cell neoplasm with hyperchromatic nuclei and brisk mitotic activity, representing [...] features.
Fibrous hamartoma of infancy with sarcomatous features. Typical triphasic fibrous hamartoma of infancy showing an abrupt transition to a highly cellular, sarcomatous spindle cell neoplasm.
Fibrous hamartoma of infancy with sarcomatous features. High-power view of the sarcomatous area showing spindled to round cells with hyperchromatic nuclei and brisk mitotic activity.
A: sarcomatous
Back Extra: Fibrous Hamartoma of Infancy
- Clinical: Fibrous hamartoma of infancy typically presents as painless solitary subcutaneous masses, sometimes with overlying skin discolouration, oedema, hypertrichosis, and tethering. About 15–25% of cases are congenital.
- Micro: The lesion has a triphasic organoid pattern with haphazardly arranged fascicles of cytologically bland fibroblastic/myofibroblastic cells, mature adipose tissue, and myxoid nodules containing primitive mesenchymal cells.
- Ancillary: Immunohistochemistry shows variable expression of SMA in the fibroblastic areas and CD34 in the primitive mesenchyme and areas with giant cell fibroblastoma–like morphology.
Reference Gallery:
Fibrous hamartoma of infancy. Low-power view showing the triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view showing the triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Giant cell fibroblastoma–like areas with abundant collagen with cracking artefact forming slit-like spaces lined by flattened tumour cells.
Fibrous hamartoma of infancy with sarcomatous features. Typical triphasic fibrous hamartoma of infancy showing an abrupt transition to a highly cellular, sarcomatous spindle cell neoplasm.
Fibrous hamartoma of infancy with sarcomatous features. High-power view of the sarcomatous area showing spindled to round cells with hyperchromatic nuclei and brisk mitotic activity.

Q: Histologically, Arteriovenous Malformation/Haemangioma is characterized by an extensive infiltration of variable-sized vessels in the subcutaneous tissue, with [...] largely outnumbering arteries.
Arteriovenous malformation/haemangioma. In some cases, cavernous vascular spaces predominate.
Arteriovenous malformation/haemangioma. There is extensive infiltration of the subcutaneous tissue by large vessels.
A: veins
Arteriovenous Malformation/Haemangioma
- Clinical: Angiography is essential for confirming the diagnosis and assessing the extent of disease in Arteriovenous Malformation/Haemangioma.
- Micro: Histologically, Arteriovenous Malformation/Haemangioma is characterized by large numbers of vessels of different sizes, including veins and arteries, with veins largely outnumbering arteries.
- Ancillary: Negative staining for GLUT1 can help distinguish Arteriovenous Malformation/Haemangioma from juvenile haemangiomas.
Reference Gallery:
Arteriovenous malformation/haemangioma. In some cases, cavernous vascular spaces predominate.
Arteriovenous malformation/haemangioma. There is extensive infiltration of the subcutaneous tissue by large vessels.
Arteriovenous malformation/haemangioma. An elastic stain (elastic Van Gieson) is useful to determine the type of vessels involved.

Q: To determine the specific types of admixed vessels involved in an Arteriovenous Malformation/Haemangioma, an ancillary [...] stain (e.g., elastic Van Gieson) is highly useful.
Arteriovenous malformation/haemangioma. An elastic stain (elastic Van Gieson) is useful to determine the type of vessels involved.
A: elastic
Arteriovenous Malformation/Haemangioma
- Clinical: Angiography is essential for confirming the diagnosis and assessing the extent of disease in Arteriovenous Malformation/Haemangioma.
- Micro: Histologically, Arteriovenous Malformation/Haemangioma is characterized by large numbers of vessels of different sizes, including veins and arteries, with veins largely outnumbering arteries.
- Ancillary: Negative staining for GLUT1 can help distinguish Arteriovenous Malformation/Haemangioma from juvenile haemangiomas.
Reference Gallery:
Arteriovenous malformation/haemangioma. In some cases, cavernous vascular spaces predominate.
Arteriovenous malformation/haemangioma. There is extensive infiltration of the subcutaneous tissue by large vessels.
Arteriovenous malformation/haemangioma. An elastic stain (elastic Van Gieson) is useful to determine the type of vessels involved.

Q: Microscopically, Acral Fibromyxoma is a lobulated tumor characterized by bland spindled and stellate cells loosely distributed in a variably [stroma type] stroma.
Acral fibromyxoma. Lobulated tumour containing a variably myxoid and collagenous stroma.
Acral fibromyxoma. The bland and uniform spindled and stellate tumour cells are loosely distributed in a fibromyxoid stroma.
Acral fibromyxoma. This cellular area is characterized by a fascicular growth of uniform spindle cells in a collagenous matrix. Note the absence of cytological atypia.
A: myxoid and collagenous
Back Extra: Acral Fibromyxoma
- Clinical: Acral fibromyxomas are typically found in middle-aged adults, more often in males, and present as painful, slowly enlarging lesions on the digits, often causing nail deformity.
- Micro: These tumours are characterized by bland spindled and stellate cells in a myxoid or collagenous stroma, with a lobulated or infiltrative growth pattern and absence of cytological atypia.
- Ancillary: Immunohistochemically, the tumour cells show strong and diffuse CD34 expression and frequent loss of RB1 expression.
Reference Gallery:
Acral fibromyxoma. Lobulated tumour containing a variably myxoid and collagenous stroma.
Acral fibromyxoma. The tumours may be predominantly myxoid and show a proliferation of small delicate vascular channels.
Acral fibromyxoma. The bland and uniform spindled and stellate tumour cells are loosely distributed in a fibromyxoid stroma.
Acral fibromyxoma. This cellular area is characterized by a fascicular growth of uniform spindle cells in a collagenous matrix. Note the absence of cytological atypia.
Acral fibromyxoma. Strong and diffuse expression of CD34.

Q: Immunohistochemically, the tumor cells of an Acral Fibromyxoma typically show strong and diffuse expression of [...], often accompanied by the loss of RB1 expression.
Acral fibromyxoma. Strong and diffuse expression of CD34.
A: CD34
Back Extra: Acral Fibromyxoma
- Clinical: Acral fibromyxomas are typically found in middle-aged adults, more often in males, and present as painful, slowly enlarging lesions on the digits, often causing nail deformity.
- Micro: These tumours are characterized by bland spindled and stellate cells in a myxoid or collagenous stroma, with a lobulated or infiltrative growth pattern and absence of cytological atypia.
- Ancillary: Immunohistochemically, the tumour cells show strong and diffuse CD34 expression and frequent loss of RB1 expression.
Reference Gallery:
Acral fibromyxoma. Lobulated tumour containing a variably myxoid and collagenous stroma.
Acral fibromyxoma. The tumours may be predominantly myxoid and show a proliferation of small delicate vascular channels.
Acral fibromyxoma. The bland and uniform spindled and stellate tumour cells are loosely distributed in a fibromyxoid stroma.
Acral fibromyxoma. This cellular area is characterized by a fascicular growth of uniform spindle cells in a collagenous matrix. Note the absence of cytological atypia.
Acral fibromyxoma. Strong and diffuse expression of CD34.

Q: Histologically, [...] is characterized by a uniform proliferation of bland spindle cells in a stroma that alternates between collagenous and myxoid areas, accompanied by a prominent network of branching thin-walled blood vessels.
Angiofibroma of soft tissue. Characteristic alternation between collagenous and myxoid areas at low magnification.
Angiofibroma of soft tissue. Uniform proliferation of neoplastic spindle cells with inconspicuous palely eosinophilic cytoplasm and short ovoid or tapering nuclei.
Angiofibroma of soft tissue. Prominent vascular network consisting of innumerable thin-walled branching blood vessels.
A: Angiofibroma of soft tissue
Back Extra: Angiofibroma of soft tissue
- Clinical: Angiofibroma of soft tissue presents as a slow-growing, painless mass, most common in middle-aged adults with a slight female predominance.
- Micro: Characterized by uniform bland spindle cells in a myxoid to collagenous stroma with a prominent network of thin-walled branching blood vessels.
- Ancillary: Detection of NCOA2 rearrangement or AHRR-NCOA2 fusion gene is a key diagnostic feature.
Reference Gallery:
Angiofibroma of soft tissue. Characteristic alternation between collagenous and myxoid areas at low magnification.
Angiofibroma of soft tissue. Uniform proliferation of neoplastic spindle cells with inconspicuous palely eosinophilic cytoplasm and short ovoid or tapering nuclei.
Angiofibroma of soft tissue. Prominent vascular network consisting of innumerable thin-walled branching blood vessels.
Angiofibroma of soft tissue. Partial karyogram showing the characteristic t(5;8)(p15;q13) that results in the AHRR-NCOA2 fusion. Arrows indicate breakpoints.

Q: A key diagnostic feature of Angiofibroma of soft tissue is a t(5;8) translocation that results in the [...] fusion gene.
Angiofibroma of soft tissue. Partial karyogram showing the characteristic t(5;8)(p15;q13) that results in the AHRR-NCOA2 fusion. Arrows indicate breakpoints.
A: AHRR-NCOA2
Back Extra: Angiofibroma of soft tissue
- Clinical: Angiofibroma of soft tissue presents as a slow-growing, painless mass, most common in middle-aged adults with a slight female predominance.
- Micro: Characterized by uniform bland spindle cells in a myxoid to collagenous stroma with a prominent network of thin-walled branching blood vessels.
- Ancillary: Detection of NCOA2 rearrangement or AHRR-NCOA2 fusion gene is a key diagnostic feature.
Reference Gallery:
Angiofibroma of soft tissue. Characteristic alternation between collagenous and myxoid areas at low magnification.
Angiofibroma of soft tissue. Uniform proliferation of neoplastic spindle cells with inconspicuous palely eosinophilic cytoplasm and short ovoid or tapering nuclei.
Angiofibroma of soft tissue. Prominent vascular network consisting of innumerable thin-walled branching blood vessels.
Angiofibroma of soft tissue. Partial karyogram showing the characteristic t(5;8)(p15;q13) that results in the AHRR-NCOA2 fusion. Arrows indicate breakpoints.

Q: Unlike aggressive angiomyxoma, Angiomyofibroblastoma is characteristically a well-[...] tumor that frequently presents as a slowly enlarging, painless mass (often mistaken for a Bartholin gland cyst).
Angiomyofibroblastoma. Angiomyofibroblastoma is typically well circumscribed.
Angiomyofibroblastoma. The tumour is more cellular and vascular than aggressive angiomyxoma. Note the adipocytic component.
A: circumscribed
Back Extra: Angiomyofibroblastoma
- Clinical: Most cases present as a slowly enlarging, painless, circumscribed mass, commonly mistaken for a Bartholin gland cyst.
- Micro: Tumours are well demarcated, with prominent vessels and a loose, oedematous stroma. Binucleated and multinucleated cells are common.
- Ancillary: Strong and diffuse positive staining for desmin is typical, with positive ER and PR expression.
Reference Gallery:
Angiomyofibroblastoma. Angiomyofibroblastoma is typically well circumscribed.
Angiomyofibroblastoma. The tumour is more cellular and vascular than aggressive angiomyxoma. Note the adipocytic component.
Angiomyofibroblastoma. Tumour cells and vessels are set in a loose oedematous stroma.
Angiomyofibroblastoma. Binucleated and multinucleated cells are frequent and may have a plasmacytoid appearance.
Angiomyofibroblastoma. In this example the tumour cells are focally clustered and have an epithelioid appearance.
Angiomyofibroblastoma. Immunopositivity for desmin is a typical feature in most cases.

Q: Microscopically, Angiomyofibroblastoma features a loose, edematous stroma with prominent vessels and frequent [...] cells that may have a plasmacytoid appearance.
Angiomyofibroblastoma. Tumour cells and vessels are set in a loose oedematous stroma.
Angiomyofibroblastoma. Binucleated and multinucleated cells are frequent and may have a plasmacytoid appearance.
A: binucleated and multinucleated
Back Extra: Angiomyofibroblastoma
- Clinical: Most cases present as a slowly enlarging, painless, circumscribed mass, commonly mistaken for a Bartholin gland cyst.
- Micro: Tumours are well demarcated, with prominent vessels and a loose, oedematous stroma. Binucleated and multinucleated cells are common.
- Ancillary: Strong and diffuse positive staining for desmin is typical, with positive ER and PR expression.
Reference Gallery:
Angiomyofibroblastoma. Angiomyofibroblastoma is typically well circumscribed.
Angiomyofibroblastoma. The tumour is more cellular and vascular than aggressive angiomyxoma. Note the adipocytic component.
Angiomyofibroblastoma. Tumour cells and vessels are set in a loose oedematous stroma.
Angiomyofibroblastoma. Binucleated and multinucleated cells are frequent and may have a plasmacytoid appearance.
Angiomyofibroblastoma. In this example the tumour cells are focally clustered and have an epithelioid appearance.
Angiomyofibroblastoma. Immunopositivity for desmin is a typical feature in most cases.

Q: Immunohistochemically, Angiomyofibroblastoma characteristically shows strong and diffuse positivity for [...], in addition to positive ER and PR expression.
Angiomyofibroblastoma. Immunopositivity for desmin is a typical feature in most cases.
A: desmin
Back Extra: Angiomyofibroblastoma
- Clinical: Most cases present as a slowly enlarging, painless, circumscribed mass, commonly mistaken for a Bartholin gland cyst.
- Micro: Tumours are well demarcated, with prominent vessels and a loose, oedematous stroma. Binucleated and multinucleated cells are common.
- Ancillary: Strong and diffuse positive staining for desmin is typical, with positive ER and PR expression.
Reference Gallery:
Angiomyofibroblastoma. Angiomyofibroblastoma is typically well circumscribed.
Angiomyofibroblastoma. The tumour is more cellular and vascular than aggressive angiomyxoma. Note the adipocytic component.
Angiomyofibroblastoma. Tumour cells and vessels are set in a loose oedematous stroma.
Angiomyofibroblastoma. Binucleated and multinucleated cells are frequent and may have a plasmacytoid appearance.
Angiomyofibroblastoma. In this example the tumour cells are focally clustered and have an epithelioid appearance.
Angiomyofibroblastoma. Immunopositivity for desmin is a typical feature in most cases.

Q: A poorly circumscribed pediatric soft tissue tumor featuring a fibromatosis-like infiltrative spindle cell component alongside nodular calcified areas containing epithelioid fibroblasts and giant cells is characteristic of [...].
Calcifying aponeurootic fibroma. The infiltrative spindle cell component is reminiscent of fibromatosis.
Calcifying aponeurootic fibroma. An infiltrative spindle cell lesion within subcutaneous fat with early matrix calcification (top left).
Calcifying aponeurootic fibroma. Calcified areas contain epithelioid fibroblasts and scattered giant cells.
A: Calcifying Aponeurootic Fibroma
Back Extra: Calcifying Aponeurootic Fibroma
- Clinical: Calcifying aponeurootic fibroma typically presents as a painless, poorly circumscribed soft tissue mass in children and adolescents, often showing calcifications on radiographic images.
- Micro: The tumor is characterized by a fibromatosis-like infiltrative component and a nodular calcified component, with plump spindle cells and calcified areas containing epithelioid fibroblasts and giant cells.
- Ancillary: Detection of the FN1-EGF gene fusion can be helpful in cases lacking calcification, though it is not required for routine diagnosis.
Reference Gallery:
Calcifying aponeurootic fibroma. The MRI shows a 1.6 cm solid mass on the plantar aspect of the foot in an 8-year-old boy.
Calcifying aponeurootic fibroma. A resection specimen with an ill-defined greyish-white lesion with a gritty consistency.
Calcifying aponeurootic fibroma. The infiltrative spindle cell component is reminiscent of fibromatosis.
Calcifying aponeurootic fibroma. An infiltrative spindle cell lesion within subcutaneous fat with early matrix calcification (top left).
Calcifying aponeurootic fibroma. Calcified areas contain epithelioid fibroblasts and scattered giant cells.
Calcifying aponeurootic fibroma. Chondroid areas may be present (decalcified specimen).

Q: On gross examination, Calcifying Aponeurootic Fibroma typically presents as an ill-defined, grayish-white mass that has a characteristic [...] consistency upon sectioning due to internal calcifications.
Calcifying aponeurootic fibroma. A resection specimen with an ill-defined greyish-white lesion with a gritty consistency.
A: gritty
Back Extra: Calcifying Aponeurootic Fibroma
- Clinical: Calcifying aponeurootic fibroma typically presents as a painless, poorly circumscribed soft tissue mass in children and adolescents, often showing calcifications on radiographic images.
- Micro: The tumor is characterized by a fibromatosis-like infiltrative component and a nodular calcified component, with plump spindle cells and calcified areas containing epithelioid fibroblasts and giant cells.
- Ancillary: Detection of the FN1-EGF gene fusion can be helpful in cases lacking calcification, though it is not required for routine diagnosis.
Reference Gallery:
Calcifying aponeurootic fibroma. The MRI shows a 1.6 cm solid mass on the plantar aspect of the foot in an 8-year-old boy.
Calcifying aponeurootic fibroma. A resection specimen with an ill-defined greyish-white lesion with a gritty consistency.
Calcifying aponeurootic fibroma. The infiltrative spindle cell component is reminiscent of fibromatosis.
Calcifying aponeurootic fibroma. An infiltrative spindle cell lesion within subcutaneous fat with early matrix calcification (top left).
Calcifying aponeurootic fibroma. Calcified areas contain epithelioid fibroblasts and scattered giant cells.
Calcifying aponeurootic fibroma. Chondroid areas may be present (decalcified specimen).

Q: Histologically, Cellular Angiofibroma features uniform spindle cells with short, stubby nuclei, frequent mast cells, and a stroma containing numerous [...] with hyalinization.
Cellular angiofibroma. Note usual circumscription, varying cellularity, and prominent vessels with hyaline walls.
Cellular angiofibroma. At high power, the spindle cells have short stubby nuclei and indistinct cytoplasm, resembling spindle cell lipoma. Note the admixed mast cells and rounded vessels.
A: thick-walled blood vessels
Back Extra: Cellular Angiofibroma
- Clinical: Cellular angiofibroma typically presents as a slow-growing, painless mass, most commonly in the vulva or inguinoscrotal regions.
- Micro: The lesion is characterized by uniform, short spindle-shaped cells in an oedematous to fibrous stroma with numerous thick-walled blood vessels and frequent mast cells.
- Ancillary: Immunohistochemical studies show CD34 expression in 30–60% of cases, and RB1 loss is frequently detected.
Reference Gallery:
Cellular angiofibroma. Note usual circumscription, varying cellularity, and prominent vessels with hyaline walls.
Cellular angiofibroma. At high power, the spindle cells have short stubby nuclei and indistinct cytoplasm, resembling spindle cell lipoma. Note the admixed mast cells and rounded vessels.
Cellular angiofibroma. Degenerative changes such as stromal oedema, patchy chronic inflammation, and mild nuclear atypia are more common in male patients.
Cellular angiofibroma. About 50% of cases contain variably prominent mature adipocytes.
Cellular angiofibroma. Rare cases show small aggregates of highly atypical cells, as here, and occasional cases may show overtly sarcomatous morphology but appear to retain benign behaviour.

Q: Approximately 50% of Cellular Angiofibroma cases feature an admixture of variably prominent, mature [...], which contributes to its morphologic overlap with spindle cell lipoma.
Cellular angiofibroma. About 50% of cases contain variably prominent mature adipocytes.
A: adipocytes
Back Extra: Cellular Angiofibroma
- Clinical: Cellular angiofibroma typically presents as a slow-growing, painless mass, most commonly in the vulva or inguinoscrotal regions.
- Micro: The lesion is characterized by uniform, short spindle-shaped cells in an oedematous to fibrous stroma with numerous thick-walled blood vessels and frequent mast cells.
- Ancillary: Immunohistochemical studies show CD34 expression in 30–60% of cases, and RB1 loss is frequently detected.
Reference Gallery:
Cellular angiofibroma. Note usual circumscription, varying cellularity, and prominent vessels with hyaline walls.
Cellular angiofibroma. At high power, the spindle cells have short stubby nuclei and indistinct cytoplasm, resembling spindle cell lipoma. Note the admixed mast cells and rounded vessels.
Cellular angiofibroma. Degenerative changes such as stromal oedema, patchy chronic inflammation, and mild nuclear atypia are more common in male patients.
Cellular angiofibroma. About 50% of cases contain variably prominent mature adipocytes.
Cellular angiofibroma. Rare cases show small aggregates of highly atypical cells, as here, and occasional cases may show overtly sarcomatous morphology but appear to retain benign behaviour.

Q: While typically uniform, Cellular Angiofibroma may exhibit degenerative changes such as stromal edema, patchy chronic inflammation, and mild nuclear atypia, which are more commonly seen in [...] patients.
Cellular angiofibroma. Degenerative changes such as stromal oedema, patchy chronic inflammation, and mild nuclear atypia are more common in male patients.
A: male
Back Extra: Cellular Angiofibroma
- Clinical: Cellular angiofibroma typically presents as a slow-growing, painless mass, most commonly in the vulva or inguinoscrotal regions.
- Micro: The lesion is characterized by uniform, short spindle-shaped cells in an oedematous to fibrous stroma with numerous thick-walled blood vessels and frequent mast cells.
- Ancillary: Immunohistochemical studies show CD34 expression in 30–60% of cases, and RB1 loss is frequently detected.
Reference Gallery:
Cellular angiofibroma. Note usual circumscription, varying cellularity, and prominent vessels with hyaline walls.
Cellular angiofibroma. At high power, the spindle cells have short stubby nuclei and indistinct cytoplasm, resembling spindle cell lipoma. Note the admixed mast cells and rounded vessels.
Cellular angiofibroma. Degenerative changes such as stromal oedema, patchy chronic inflammation, and mild nuclear atypia are more common in male patients.
Cellular angiofibroma. About 50% of cases contain variably prominent mature adipocytes.
Cellular angiofibroma. Rare cases show small aggregates of highly atypical cells, as here, and occasional cases may show overtly sarcomatous morphology but appear to retain benign behaviour.

Q: Histologically, Desmoplastic fibroblastoma is a paucicellular tumor composed of a myxocollagenous matrix with scattered, bland fibroblasts that frequently exhibit a characteristic [...] shape.
Desmoplastic fibroblastoma. The tumour is paucicellular and composed of uniform, often stellate-shaped, fibroblasts.
Desmoplastic fibroblastoma. The tumour is paucicellular and composed of uniform, often stellate-shaped, fibroblasts.
A: stellate
Back Extra: Desmoplastic fibroblastoma
- Clinical: Desmoplastic fibroblastoma typically presents as an asymptomatic, slow-growing subcutaneous mass, often in the upper arm, shoulder, lower limb, back, forearm, hand, or foot.
- Micro: The tumour is paucicellular, with a myxocollagenous matrix and scattered, bland, stellate-shaped and spindled fibroblastic cells.
- Ancillary: Deregulated expression of FOSL1 is seen in desmoplastic fibroblastoma, typically due to a t(2;11)(q31;q12) chromosomal translocation.
Reference Gallery:
Desmoplastic fibroblastoma. The lesion is well circumscribed with a smooth rounded border.
Desmoplastic fibroblastoma. The tumour is paucicellular and composed of uniform, often stellate-shaped, fibroblasts.
Desmoplastic fibroblastoma. The tumour is paucicellular and composed of uniform, often stellate-shaped, fibroblasts.

Q: On low-power examination, Desmoplastic fibroblastoma characteristically presents as a well-circumscribed subcutaneous tumor with a smooth, [...].
Desmoplastic fibroblastoma. The lesion is well circumscribed with a smooth rounded border.
A: rounded border
Back Extra: Desmoplastic fibroblastoma
- Clinical: Desmoplastic fibroblastoma typically presents as an asymptomatic, slow-growing subcutaneous mass, often in the upper arm, shoulder, lower limb, back, forearm, hand, or foot.
- Micro: The tumour is paucicellular, with a myxocollagenous matrix and scattered, bland, stellate-shaped and spindled fibroblastic cells.
- Ancillary: Deregulated expression of FOSL1 is seen in desmoplastic fibroblastoma, typically due to a t(2;11)(q31;q12) chromosomal translocation.
Reference Gallery:
Desmoplastic fibroblastoma. The lesion is well circumscribed with a smooth rounded border.
Desmoplastic fibroblastoma. The tumour is paucicellular and composed of uniform, often stellate-shaped, fibroblasts.
Desmoplastic fibroblastoma. The tumour is paucicellular and composed of uniform, often stellate-shaped, fibroblasts.

Q: Elastofibroma typically presents as a slow-growing, asymptomatic mass most commonly located in the [...] region of elderly patients.
Elastofibroma. Axial T1-weighted MRI showing an inhomogeneous lesion with low and streaky high signal intensities (arrows) in the back.
Elastofibroma. An ill-defined mass comprising an admixture of greyish-white fibrous tissue and intervening yellow fat.
A: scapular
Back Extra: Elastofibroma
- Clinical: Elastofibroma typically presents as a slow-growing, asymptomatic mass in the scapular region of elderly patients, with a strong female predominance.
- Micro: The lesion is characterized by hypocellular fibrocollagenous tissue with thick, deeply eosinophilic elastic fibres arranged in beaded strings or globules.
- Ancillary: Chromosomal instability, including gains and losses in specific regions, has been observed, but is not clinically relevant for diagnosis.
Reference Gallery:
Elastofibroma. Axial T1-weighted MRI showing an inhomogeneous lesion with low and streaky high signal intensities (arrows) in the back.
Elastofibroma. An ill-defined mass comprising an admixture of greyish-white fibrous tissue and intervening yellow fat.
Elastofibroma. Hypocellular fibrocollagenous tissue with mature adipose tissue.
Elastofibroma. Thick or coarse, deeply eosinophilic elastic fibres arranged in beaded strings or globules.
Elastofibroma. Elastic-Masson staining highlights the abnormal elastic fibres.

Q: The microscopic hallmark of an elastofibroma is hypocellular fibrocollagenous tissue containing thick, deeply eosinophilic elastic fibers that are characteristically arranged in [...].
Elastofibroma. Hypocellular fibrocollagenous tissue with mature adipose tissue.
Elastofibroma. Thick or coarse, deeply eosinophilic elastic fibres arranged in beaded strings or globules.
A: beaded strings or globules
Back Extra: Elastofibroma
- Clinical: Elastofibroma typically presents as a slow-growing, asymptomatic mass in the scapular region of elderly patients, with a strong female predominance.
- Micro: The lesion is characterized by hypocellular fibrocollagenous tissue with thick, deeply eosinophilic elastic fibres arranged in beaded strings or globules.
- Ancillary: Chromosomal instability, including gains and losses in specific regions, has been observed, but is not clinically relevant for diagnosis.
Reference Gallery:
Elastofibroma. Axial T1-weighted MRI showing an inhomogeneous lesion with low and streaky high signal intensities (arrows) in the back.
Elastofibroma. An ill-defined mass comprising an admixture of greyish-white fibrous tissue and intervening yellow fat.
Elastofibroma. Hypocellular fibrocollagenous tissue with mature adipose tissue.
Elastofibroma. Thick or coarse, deeply eosinophilic elastic fibres arranged in beaded strings or globules.
Elastofibroma. Elastic-Masson staining highlights the abnormal elastic fibres.

Q: To highlight the characteristic abnormal elastic fibers in an elastofibroma, an [...] stain can be utilized.
Elastofibroma. Elastic-Masson staining highlights the abnormal elastic fibres.
A: Elastic-Masson
Back Extra: Elastofibroma
- Clinical: Elastofibroma typically presents as a slow-growing, asymptomatic mass in the scapular region of elderly patients, with a strong female predominance.
- Micro: The lesion is characterized by hypocellular fibrocollagenous tissue with thick, deeply eosinophilic elastic fibres arranged in beaded strings or globules.
- Ancillary: Chromosomal instability, including gains and losses in specific regions, has been observed, but is not clinically relevant for diagnosis.
Reference Gallery:
Elastofibroma. Axial T1-weighted MRI showing an inhomogeneous lesion with low and streaky high signal intensities (arrows) in the back.
Elastofibroma. An ill-defined mass comprising an admixture of greyish-white fibrous tissue and intervening yellow fat.
Elastofibroma. Hypocellular fibrocollagenous tissue with mature adipose tissue.
Elastofibroma. Thick or coarse, deeply eosinophilic elastic fibres arranged in beaded strings or globules.
Elastofibroma. Elastic-Masson staining highlights the abnormal elastic fibres.

Q: Clinically, Fibroma of tendon sheath typically presents as a smooth, nodular mass most commonly attached to the tendons of the [...].
Fibroma of tendon sheath. Intraoperative photo showing the smooth nodular surface and attachment to a tendon.
A: fingers
Back Extra: Fibroma of tendon sheath
- Clinical: Fibroma of tendon sheath is a rare, benign lesion typically involving the finger tendons, especially the thumb, index finger, and middle finger.
- Micro: The lesion is well-circumscribed, containing bland spindle cells in a collagenous stroma with characteristic slit-like thin-walled vessels.
- Ancillary: USP6 rearrangement can be found in some cellular subtypes of fibroma of tendon sheath, aiding in distinguishing it from other benign fibroblastic lesions.
Reference Gallery:
Fibroma of tendon sheath. Intraoperative photo showing the smooth nodular surface and attachment to a tendon.
Fibroma of tendon sheath. Low-power view showing the highly sclerotic and hypocellular appearances. Note the small vessels and clefts.
Fibroma of tendon sheath. Some cases can show increased cellularity, which is most obvious at the edge.
Fibroma of tendon sheath. The tumour is well circumscribed and is composed of bland spindle cells with a prominent collagenous stroma and slit-like, thin-walled blood vessels.
Fibroma of tendon sheath. The tumour cells contain fine chromatin and indistinct pale cytoplasm. Note the collagenous stroma and thin-walled blood vessel.
Fibroma of tendon sheath. This lower-power view shows characteristic variation in cellularity.

Q: Histologically, Fibroma of tendon sheath features bland spindle cells in a highly collagenous stroma with characteristic [...] thin-walled blood vessels.
Fibroma of tendon sheath. Low-power view showing the highly sclerotic and hypocellular appearances. Note the small vessels and clefts.
Fibroma of tendon sheath. The tumour is well circumscribed and is composed of bland spindle cells with a prominent collagenous stroma and slit-like, thin-walled blood vessels.
A: slit-like
Back Extra: Fibroma of tendon sheath
- Clinical: Fibroma of tendon sheath is a rare, benign lesion typically involving the finger tendons, especially the thumb, index finger, and middle finger.
- Micro: The lesion is well-circumscribed, containing bland spindle cells in a collagenous stroma with characteristic slit-like thin-walled vessels.
- Ancillary: USP6 rearrangement can be found in some cellular subtypes of fibroma of tendon sheath, aiding in distinguishing it from other benign fibroblastic lesions.
Reference Gallery:
Fibroma of tendon sheath. Intraoperative photo showing the smooth nodular surface and attachment to a tendon.
Fibroma of tendon sheath. Low-power view showing the highly sclerotic and hypocellular appearances. Note the small vessels and clefts.
Fibroma of tendon sheath. Some cases can show increased cellularity, which is most obvious at the edge.
Fibroma of tendon sheath. The tumour is well circumscribed and is composed of bland spindle cells with a prominent collagenous stroma and slit-like, thin-walled blood vessels.
Fibroma of tendon sheath. The tumour cells contain fine chromatin and indistinct pale cytoplasm. Note the collagenous stroma and thin-walled blood vessel.
Fibroma of tendon sheath. This lower-power view shows characteristic variation in cellularity.

Q: Some cellular subtypes of Fibroma of tendon sheath can be distinguished from other benign fibroblastic lesions by the presence of a [...] gene rearrangement.
Fibroma of tendon sheath. Some cases can show increased cellularity, which is most obvious at the edge.
Fibroma of tendon sheath. This lower-power view shows characteristic variation in cellularity.
A: USP6
Back Extra: Fibroma of tendon sheath
- Clinical: Fibroma of tendon sheath is a rare, benign lesion typically involving the finger tendons, especially the thumb, index finger, and middle finger.
- Micro: The lesion is well-circumscribed, containing bland spindle cells in a collagenous stroma with characteristic slit-like thin-walled vessels.
- Ancillary: USP6 rearrangement can be found in some cellular subtypes of fibroma of tendon sheath, aiding in distinguishing it from other benign fibroblastic lesions.
Reference Gallery:
Fibroma of tendon sheath. Intraoperative photo showing the smooth nodular surface and attachment to a tendon.
Fibroma of tendon sheath. Low-power view showing the highly sclerotic and hypocellular appearances. Note the small vessels and clefts.
Fibroma of tendon sheath. Some cases can show increased cellularity, which is most obvious at the edge.
Fibroma of tendon sheath. The tumour is well circumscribed and is composed of bland spindle cells with a prominent collagenous stroma and slit-like, thin-walled blood vessels.
Fibroma of tendon sheath. The tumour cells contain fine chromatin and indistinct pale cytoplasm. Note the collagenous stroma and thin-walled blood vessel.
Fibroma of tendon sheath. This lower-power view shows characteristic variation in cellularity.

Q: In Fibromatosis colli (typically presenting as a mass in the sternocleidomastoid muscle), histology classically demonstrates a paucicellular, scar-like fibroblastic proliferation entrapping atrophic [...].
Fibromatosis colli. Paucicellular, scar-like fibroblastic proliferation entrapping atrophic skeletal muscle.
Fibromatosis colli. Paucicellular, scar-like fibroblastic proliferation entrapping atrophic skeletal muscle.
A: skeletal muscle
Back Extra: Fibromatosis colli
- Clinical: Fibromatosis colli presents as a mass within the sternocleidomastoid muscle, most often congenitally or within the first 2–4 weeks of life. It can lead to torticollis and plagiocephaly.
- Micro: Histologically, fibromatosis colli demonstrates a paucicellular, scar-like fibroblastic proliferation entrapping atrophic skeletal muscle.
- Ancillary: Ultrasound is the preferred imaging method, showing an isoechoic to hypoechoic solid, well-defined ovoid mass in continuity with the sternocleidomastoid muscle.
Reference Gallery:
Fibromatosis colli. Paucicellular, scar-like fibroblastic proliferation entrapping atrophic skeletal muscle.
Fibromatosis colli. Paucicellular, scar-like fibroblastic proliferation entrapping atrophic skeletal muscle.

Q: In Gardner Fibroma, the characteristic haphazardly arranged coarse collagen fibers are separated by distinctive [...] that contain sparse bland spindle cells.
Gardner fibroma. Small bland spindle cells are dispersed in cracks between collagen fibres.
A: clefts or cracks
Back Extra: Gardner Fibroma
- Clinical: Gardner fibroma typically presents as a painless mass in children < 10 years old, commonly in the superficial and deep soft tissues of the torso or head/neck region.
- Micro: Characterized by haphazardly arranged coarse collagen fibres with characteristic clefts or cracks, few inconspicuous spindle cells, and entrapment of adipose tissue and neurovascular bundles.
- Ancillary: Immunohistochemistry shows CD34 positivity and nuclear accumulation of β-catenin, particularly in cases associated with familial adenomatous polyposis (FAP).
Reference Gallery:
Gardner fibroma. Small bland spindle cells are dispersed in cracks between collagen fibres.
Gardner fibroma. Entrapped mature adipose tissue and benign nerve fibres are frequently seen in Gardner fibroma.

Q: In addition to coarse collagen, Gardner Fibroma frequently exhibits entrapment of mature [...] and benign neurovascular bundles within the stroma.
Gardner fibroma. Entrapped mature adipose tissue and benign nerve fibres are frequently seen in Gardner fibroma.
A: adipose tissue
Back Extra: Gardner Fibroma
- Clinical: Gardner fibroma typically presents as a painless mass in children < 10 years old, commonly in the superficial and deep soft tissues of the torso or head/neck region.
- Micro: Characterized by haphazardly arranged coarse collagen fibres with characteristic clefts or cracks, few inconspicuous spindle cells, and entrapment of adipose tissue and neurovascular bundles.
- Ancillary: Immunohistochemistry shows CD34 positivity and nuclear accumulation of β-catenin, particularly in cases associated with familial adenomatous polyposis (FAP).
Reference Gallery:
Gardner fibroma. Small bland spindle cells are dispersed in cracks between collagen fibres.
Gardner fibroma. Entrapped mature adipose tissue and benign nerve fibres are frequently seen in Gardner fibroma.

Q: A dome-shaped or polypoid cutaneous nodule on the digit of a young child that microscopically shows bland spindle cells with prominent eosinophilic intracytoplasmic inclusions is characteristic of [...].
Inclusion body fibromatosis. A single protuberant nodule with an erythematous surface on the lateral aspect of the distal toe.
Inclusion body fibromatosis. High-power view demonstrates spindle cells with elongated, cytologically bland nuclei and rounded, eosinophilic, intracytoplasmic inclusions, some indenting the nucleus.
A: Inclusion Body Fibromatosis
Back Extra: Inclusion Body Fibromatosis
- Clinical: Inclusion Body Fibromatosis typically presents as a dome-shaped or polypoid cutaneous nodule, usually no larger than 2 cm, and is most commonly found in children under 5 years of age.
- Micro: Characterized by spindle cells with elongated, cytologically bland nuclei and prominent eosinophilic intracytoplasmic inclusions, which are frequently paranuclear and may indent the nucleus.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Inclusion Body Fibromatosis.
Reference Gallery:
Inclusion body fibromatosis. High-power view demonstrates spindle cells with elongated, cytologically bland nuclei and rounded, eosinophilic, intracytoplasmic inclusions, some indenting the nucleus.
Inclusion body fibromatosis. A single protuberant nodule with an erythematous surface on the lateral aspect of the distal toe.
Inclusion body fibromatosis. Gomori trichrome staining highlights intracytoplasmic inclusions (red).
Inclusion body fibromatosis. Immunostaining for SMA demonstrates a peripheral (tram-track) pattern of expression.
Inclusion body fibromatosis. Ultrastructurally, myofilamentous bundles at the periphery of a tumour cell merge with a dense intracytoplasmic inclusion.
Inclusion body fibromatosis. Spindled cells in short fascicles and whorls surrounding adnexa are a characteristic growth pattern.

Q: The microscopic hallmark of Inclusion Body Fibromatosis is the presence of bland spindle cells arranged in short fascicles containing prominent, rounded [...] that frequently indent the nucleus.
Inclusion body fibromatosis. High-power view demonstrates spindle cells with elongated, cytologically bland nuclei and rounded, eosinophilic, intracytoplasmic inclusions, some indenting the nucleus.
Inclusion body fibromatosis. Spindled cells in short fascicles and whorls surrounding adnexa are a characteristic growth pattern.
A: eosinophilic intracytoplasmic inclusions
Back Extra: Inclusion Body Fibromatosis
- Clinical: Inclusion Body Fibromatosis typically presents as a dome-shaped or polypoid cutaneous nodule, usually no larger than 2 cm, and is most commonly found in children under 5 years of age.
- Micro: Characterized by spindle cells with elongated, cytologically bland nuclei and prominent eosinophilic intracytoplasmic inclusions, which are frequently paranuclear and may indent the nucleus.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Inclusion Body Fibromatosis.
Reference Gallery:
Inclusion body fibromatosis. High-power view demonstrates spindle cells with elongated, cytologically bland nuclei and rounded, eosinophilic, intracytoplasmic inclusions, some indenting the nucleus.
Inclusion body fibromatosis. A single protuberant nodule with an erythematous surface on the lateral aspect of the distal toe.
Inclusion body fibromatosis. Gomori trichrome staining highlights intracytoplasmic inclusions (red).
Inclusion body fibromatosis. Immunostaining for SMA demonstrates a peripheral (tram-track) pattern of expression.
Inclusion body fibromatosis. Ultrastructurally, myofilamentous bundles at the periphery of a tumour cell merge with a dense intracytoplasmic inclusion.
Inclusion body fibromatosis. Spindled cells in short fascicles and whorls surrounding adnexa are a characteristic growth pattern.

Q: In Inclusion Body Fibromatosis, the characteristic intracytoplasmic inclusions are classically highlighted in red when evaluated with a [...] special stain.
Inclusion body fibromatosis. Gomori trichrome staining highlights intracytoplasmic inclusions (red).
A: Gomori trichrome
Back Extra: Inclusion Body Fibromatosis
- Clinical: Inclusion Body Fibromatosis typically presents as a dome-shaped or polypoid cutaneous nodule, usually no larger than 2 cm, and is most commonly found in children under 5 years of age.
- Micro: Characterized by spindle cells with elongated, cytologically bland nuclei and prominent eosinophilic intracytoplasmic inclusions, which are frequently paranuclear and may indent the nucleus.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Inclusion Body Fibromatosis.
Reference Gallery:
Inclusion body fibromatosis. High-power view demonstrates spindle cells with elongated, cytologically bland nuclei and rounded, eosinophilic, intracytoplasmic inclusions, some indenting the nucleus.
Inclusion body fibromatosis. A single protuberant nodule with an erythematous surface on the lateral aspect of the distal toe.
Inclusion body fibromatosis. Gomori trichrome staining highlights intracytoplasmic inclusions (red).
Inclusion body fibromatosis. Immunostaining for SMA demonstrates a peripheral (tram-track) pattern of expression.
Inclusion body fibromatosis. Ultrastructurally, myofilamentous bundles at the periphery of a tumour cell merge with a dense intracytoplasmic inclusion.
Inclusion body fibromatosis. Spindled cells in short fascicles and whorls surrounding adnexa are a characteristic growth pattern.

Q: The classic histologic finding in Juvenile Hyaline Fibromatosis consists of cords of fibroblasts embedded in an abundant background of [...].
Juvenile hyaline fibromatosis. Cords of fibroblasts in a background of abundant amorphous hyaline material.
Juvenile hyaline fibromatosis. Dermal-based band-like deposits of hyaline matrix with obliteration of normal adnexal structures.
A: amorphous hyaline material
Back Extra: Juvenile Hyaline Fibromatosis
- Clinical: Juvenile hyaline fibromatosis typically presents in infancy with subcutaneous/soft tissue nodules, papules, gingival hypertrophy, and joint contractures.
- Micro: Characterized by cords of fibroblasts in a background of abundant amorphous hyaline material, which stains strongly with PAS and is diastase-resistant.
- Ancillary: Germline sequencing of the ANTXR2 gene can confirm the diagnosis, as this gene encodes a protein that binds laminin and collagen VI.
Reference Gallery:
Juvenile hyaline fibromatosis. Cords of fibroblasts in a background of abundant amorphous hyaline material.
Juvenile hyaline fibromatosis. Cords of fibroblasts in a background of abundant amorphous hyaline material (PASD staining).
Juvenile hyaline fibromatosis. Dermal-based band-like deposits of hyaline matrix with obliteration of normal adnexal structures.
Juvenile hyaline fibromatosis. Dermal-based band-like and subcutaneous nodular deposits of avidly PAS-positive hyaline material (PASD staining).

Q: In Juvenile Hyaline Fibromatosis, the characteristic dermal and subcutaneous hyaline deposits strongly highlight with the PAS stain and are [...]-resistant.
Juvenile hyaline fibromatosis. Cords of fibroblasts in a background of abundant amorphous hyaline material (PASD staining).
Juvenile hyaline fibromatosis. Dermal-based band-like and subcutaneous nodular deposits of avidly PAS-positive hyaline material (PASD staining).
A: diastase
Back Extra: Juvenile Hyaline Fibromatosis
- Clinical: Juvenile hyaline fibromatosis typically presents in infancy with subcutaneous/soft tissue nodules, papules, gingival hypertrophy, and joint contractures.
- Micro: Characterized by cords of fibroblasts in a background of abundant amorphous hyaline material, which stains strongly with PAS and is diastase-resistant.
- Ancillary: Germline sequencing of the ANTXR2 gene can confirm the diagnosis, as this gene encodes a protein that binds laminin and collagen VI.
Reference Gallery:
Juvenile hyaline fibromatosis. Cords of fibroblasts in a background of abundant amorphous hyaline material.
Juvenile hyaline fibromatosis. Cords of fibroblasts in a background of abundant amorphous hyaline material (PASD staining).
Juvenile hyaline fibromatosis. Dermal-based band-like deposits of hyaline matrix with obliteration of normal adnexal structures.
Juvenile hyaline fibromatosis. Dermal-based band-like and subcutaneous nodular deposits of avidly PAS-positive hyaline material (PASD staining).

Q: An infant presenting with subcutaneous nodules, joint contractures, and gingival hypertrophy is found to have dermal deposits of PAS-positive, amorphous matrix. This presentation is highly characteristic of [...].
Juvenile hyaline fibromatosis. Cords of fibroblasts in a background of abundant amorphous hyaline material.
Juvenile hyaline fibromatosis. Dermal-based band-like and subcutaneous nodular deposits of avidly PAS-positive hyaline material (PASD staining).
A: Juvenile Hyaline Fibromatosis
Back Extra: Juvenile Hyaline Fibromatosis
- Clinical: Juvenile hyaline fibromatosis typically presents in infancy with subcutaneous/soft tissue nodules, papules, gingival hypertrophy, and joint contractures.
- Micro: Characterized by cords of fibroblasts in a background of abundant amorphous hyaline material, which stains strongly with PAS and is diastase-resistant.
- Ancillary: Germline sequencing of the ANTXR2 gene can confirm the diagnosis, as this gene encodes a protein that binds laminin and collagen VI.
Reference Gallery:
Juvenile hyaline fibromatosis. Cords of fibroblasts in a background of abundant amorphous hyaline material.
Juvenile hyaline fibromatosis. Cords of fibroblasts in a background of abundant amorphous hyaline material (PASD staining).
Juvenile hyaline fibromatosis. Dermal-based band-like deposits of hyaline matrix with obliteration of normal adnexal structures.
Juvenile hyaline fibromatosis. Dermal-based band-like and subcutaneous nodular deposits of avidly PAS-positive hyaline material (PASD staining).

Q: In myofibroblastoma, the classic histologic appearance consists of bland spindle cells intersected by prominent bands of [...], frequently accompanied by an admixture of mature adipocytes.
Myofibroblastoma. Proliferation of bland spindle cells with interspersed bands of hyalinized collagen.
Myofibroblastoma. A fibrofatty tumour with spindle cell lipoma–like morphology: admixture of mature adipocytes with bland spindle cells set in a fibrous stroma.
A: hyalinized collagen
Back Extra: Myofibroblastoma
- Clinical: Myofibroblastomas typically present as painless masses in adults, with a male predominance and a median age of 54 years.
- Micro: The tumour is characterized by spindle cells with bland nuclei, bands of hyalinized collagen, and a variable admixture of mature adipocytes.
- Ancillary: Immunohistochemistry shows diffuse coexpression of desmin and CD34, with about 90% of cases showing loss of nuclear RB1.
Reference Gallery:
Myofibroblastoma. Proliferation of bland spindle cells with interspersed bands of hyalinized collagen.
Myofibroblastoma. This tumour contains a lipomatous component. Low magnification showing well-circumscribed borders.
Myofibroblastoma. A fibrofatty tumour with spindle cell lipoma–like morphology: admixture of mature adipocytes with bland spindle cells set in a fibrous stroma.
Myofibroblastoma. Proliferation of spindle cells with formation of Verocay-like bodies, mimicking schwannoma.
Myofibroblastoma. Neoplastic cells showing round cell morphology: the presence of bands of hyalinized collagen and the absence of mitoses and nuclear atypia are helpful diagnostic features.
Myofibroblastoma. This tumour shows degenerative features, exhibiting cells with moderate nuclear atypia. Mitoses and necrosis are absent.
Myofibroblastoma. Neoplastic cells may exhibit epithelioid cell morphology with a pseudoinfiltrative growth pattern.
Myofibroblastoma. Neoplastic cells showing multifocal staining for desmin (immunoperoxidase staining).
Myofibroblastoma. Diffuse expression of CD34 by neoplastic cells (immunoperoxidase staining).
Myofibroblastoma. Loss of nuclear RB1, maintained in endothelial and inflammatory cells.

Q: The diagnosis of myofibroblastoma is supported by immunohistochemical coexpression of CD34 and desmin, along with the highly specific loss of nuclear [...].
Myofibroblastoma. Neoplastic cells showing multifocal staining for desmin (immunoperoxidase staining).
Myofibroblastoma. Diffuse expression of CD34 by neoplastic cells (immunoperoxidase staining).
Myofibroblastoma. Loss of nuclear RB1, maintained in endothelial and inflammatory cells.
A: RB1
Back Extra: Myofibroblastoma
- Clinical: Myofibroblastomas typically present as painless masses in adults, with a male predominance and a median age of 54 years.
- Micro: The tumour is characterized by spindle cells with bland nuclei, bands of hyalinized collagen, and a variable admixture of mature adipocytes.
- Ancillary: Immunohistochemistry shows diffuse coexpression of desmin and CD34, with about 90% of cases showing loss of nuclear RB1.
Reference Gallery:
Myofibroblastoma. Proliferation of bland spindle cells with interspersed bands of hyalinized collagen.
Myofibroblastoma. This tumour contains a lipomatous component. Low magnification showing well-circumscribed borders.
Myofibroblastoma. A fibrofatty tumour with spindle cell lipoma–like morphology: admixture of mature adipocytes with bland spindle cells set in a fibrous stroma.
Myofibroblastoma. Proliferation of spindle cells with formation of Verocay-like bodies, mimicking schwannoma.
Myofibroblastoma. Neoplastic cells showing round cell morphology: the presence of bands of hyalinized collagen and the absence of mitoses and nuclear atypia are helpful diagnostic features.
Myofibroblastoma. This tumour shows degenerative features, exhibiting cells with moderate nuclear atypia. Mitoses and necrosis are absent.
Myofibroblastoma. Neoplastic cells may exhibit epithelioid cell morphology with a pseudoinfiltrative growth pattern.
Myofibroblastoma. Neoplastic cells showing multifocal staining for desmin (immunoperoxidase staining).
Myofibroblastoma. Diffuse expression of CD34 by neoplastic cells (immunoperoxidase staining).
Myofibroblastoma. Loss of nuclear RB1, maintained in endothelial and inflammatory cells.

Q: Histologically, Nodular Fasciitis features plump spindle-shaped cells arranged in a loose myxoid stroma, classically described as having a [...] appearance.
Nodular fasciitis. At medium power, the characteristic tissue culture–like appearance and cystic myxoid changes are virtually diagnostic.
Nodular fasciitis. The tumour cells contain ovoid to tapering nuclei, fine chromatin, small nucleoli, and amphophilic cytoplasm. Note the loose fascicular architecture and prominent mitotic activity.
A: tissue culture-like
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis typically grows rapidly over 2-3 months, often presenting as a subcutaneous mass ≤ 2 cm in size, which may be sore or tender.
- Micro: Nodular fasciitis is characterized by plump spindle-shaped cells with a tissue culture–like appearance, myxoid stroma, and prominent mitotic activity.
- Ancillary: USP6 rearrangements can be detected using break-apart USP6 FISH or next-generation sequencing, confirming the diagnosis of nodular fasciitis.
Reference Gallery:
Nodular fasciitis. Nodularity, vague irregular borders, myxoid and cystic changes, and haemorrhagic areas are readily observed at low power in this typical example.
Nodular fasciitis. At medium power, the characteristic tissue culture–like appearance and cystic myxoid changes are virtually diagnostic.
Nodular fasciitis. Hyalinized areas are commonly encountered.
Nodular fasciitis. Occasional cases are intravascular.
Nodular fasciitis. The tumour cells contain ovoid to tapering nuclei, fine chromatin, small nucleoli, and amphophilic cytoplasm. Note the loose fascicular architecture and prominent mitotic activity.

Q: Nodular Fasciitis is a benign, rapidly growing spindle cell tumor that is genetically characterized by rearrangements involving the [...] gene.
Nodular fasciitis. Nodularity, vague irregular borders, myxoid and cystic changes, and haemorrhagic areas are readily observed at low power in this typical example.
A: USP6
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis typically grows rapidly over 2-3 months, often presenting as a subcutaneous mass ≤ 2 cm in size, which may be sore or tender.
- Micro: Nodular fasciitis is characterized by plump spindle-shaped cells with a tissue culture–like appearance, myxoid stroma, and prominent mitotic activity.
- Ancillary: USP6 rearrangements can be detected using break-apart USP6 FISH or next-generation sequencing, confirming the diagnosis of nodular fasciitis.
Reference Gallery:
Nodular fasciitis. Nodularity, vague irregular borders, myxoid and cystic changes, and haemorrhagic areas are readily observed at low power in this typical example.
Nodular fasciitis. At medium power, the characteristic tissue culture–like appearance and cystic myxoid changes are virtually diagnostic.
Nodular fasciitis. Hyalinized areas are commonly encountered.
Nodular fasciitis. Occasional cases are intravascular.
Nodular fasciitis. The tumour cells contain ovoid to tapering nuclei, fine chromatin, small nucleoli, and amphophilic cytoplasm. Note the loose fascicular architecture and prominent mitotic activity.

Q: Despite its benign nature, Nodular Fasciitis can mimic malignancy due to its rapid clinical growth and histologically prominent [...] (without atypia).
Nodular fasciitis. The tumour cells contain ovoid to tapering nuclei, fine chromatin, small nucleoli, and amphophilic cytoplasm. Note the loose fascicular architecture and prominent mitotic activity.
A: mitotic activity
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis typically grows rapidly over 2-3 months, often presenting as a subcutaneous mass ≤ 2 cm in size, which may be sore or tender.
- Micro: Nodular fasciitis is characterized by plump spindle-shaped cells with a tissue culture–like appearance, myxoid stroma, and prominent mitotic activity.
- Ancillary: USP6 rearrangements can be detected using break-apart USP6 FISH or next-generation sequencing, confirming the diagnosis of nodular fasciitis.
Reference Gallery:
Nodular fasciitis. Nodularity, vague irregular borders, myxoid and cystic changes, and haemorrhagic areas are readily observed at low power in this typical example.
Nodular fasciitis. At medium power, the characteristic tissue culture–like appearance and cystic myxoid changes are virtually diagnostic.
Nodular fasciitis. Hyalinized areas are commonly encountered.
Nodular fasciitis. Occasional cases are intravascular.
Nodular fasciitis. The tumour cells contain ovoid to tapering nuclei, fine chromatin, small nucleoli, and amphophilic cytoplasm. Note the loose fascicular architecture and prominent mitotic activity.

Q: Histologically, [...] presents as a paucicellular lesion composed of bland spindled fibroblasts and thick, haphazardly arranged collagen fibers that characteristically entrap surrounding adipose tissue and skeletal muscle.
Nuchal-type fibroma. The tumour is paucicellular and contains thick haphazardly arranged collagen fibres entrapping adipose tissue and peripheral nerves.
Nuchal-type fibroma. The lesional cells are bland spindled fibroblasts. Extension into skeletal muscle is common.
A: Nuchal-Type Fibroma
Back Extra: Nuchal-Type Fibroma
- Clinical: Nuchal-type fibroma is significantly more common in men, with a peak incidence in the fourth and fifth decades of life, and up to 50% of patients have diabetes mellitus.
- Micro: Nuchal-type fibroma is a paucicellular lesion composed of bland spindle cells, thick haphazardly arranged collagen fibres, and entrapped subcutaneous adipose tissue.
- Ancillary: The spindled fibroblasts in nuchal-type fibroma are CD34-positive and negative for β-catenin by immunohistochemistry.
Reference Gallery:
Nuchal-type fibroma. The tumour is paucicellular and contains thick haphazardly arranged collagen fibres entrapping adipose tissue and peripheral nerves.
Nuchal-type fibroma. The lesional cells are bland spindled fibroblasts. Extension into skeletal muscle is common.

Q: The diagnostic molecular hallmark of Dermatofibrosarcoma Protuberans is a translocation involving chromosomes 17 and 22, resulting in the [...] gene fusion.
Dermatofibrosarcoma protuberans. The classic G-banded karyotype shows two supernumerary chromosomes (arrows).
Dermatofibrosarcoma protuberans. Multiplexed spectral in situ hybridization of a chromosomal spread shows supernumerary chromosomes pseudocoloured to demonstrate material from both 22 and 17, in pink and blue, respectively (asterisks).
A: COL1A1-PDGFB
Back Extra: Dermatofibrosarcoma Protuberans
- Clinical: Dermatofibrosarcoma protuberans typically presents as a nodular or multinodular cutaneous mass, often with a history of slow but persistent growth. Early lesions may show a plaque-like growth with peripheral red discolouration.
- Micro: Classic DFSP is characterized by a diffuse infiltration of dermis and subcutis, with a honeycomb appearance. The tumour cells are cytologically uniform spindled cells arranged in a storiform pattern.
- Ancillary: Immunohistochemistry shows strong CD34 positivity in tumour cells, which can help differentiate DFSP from other fibroblastic tumours. The detection of the COL1A1-PDGFB fusion is also crucial for diagnosis.
Reference Gallery:
Dermatofibrosarcoma protuberans. Giant dermatofibrosarcoma protuberans presenting clinically as a huge exophytic, multinodular mass with focal ulceration.
Dermatofibrosarcoma protuberans. A case containing numerous blood vessels mimicking a vascular lesion.
Dermatofibrosarcoma protuberans. Increased cytological atypia and increased proliferative activity are seen in fibrosarcomatous areas.
Dermatofibrosarcoma protuberans. Pigmented cells are seen in addition to fibroblastic tumour cells.
Dermatofibrosarcoma protuberans. A diffusely infiltrating myxoid neoplasm with numerous vessels with slightly fibrosed vessel walls is seen.
Dermatofibrosarcoma protuberans. An example with focal myoid differentiation, showing a proliferation of eosinophilic spindled tumour cells set in a hyalinized stroma.
Dermatofibrosarcoma protuberans. Flat, plaque-like dermatofibrosarcoma protuberans mimicking a benign dermal neoplasm.
Dermatofibrosarcoma protuberans. A 4-year-old boy with known adenosine deaminase–deficient severe combined immunodeficiency developed multiple flat dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans. A hypocellular example of flat dermatofibrosarcoma protuberans is seen in this young patient with known adenosine deaminase–deficient severe combined immunodeficiency.
Dermatofibrosarcoma protuberans. The classic G-banded karyotype shows two supernumerary chromosomes (arrows).
Dermatofibrosarcoma protuberans. Multiplexed spectral in situ hybridization of a chromosomal spread shows supernumerary chromosomes pseudocoloured to demonstrate material from both 22 and 17, in pink and blue, respectively (asterisks).
Dermatofibrosarcoma protuberans. Cross-sectioning reveals a firm fibrous tumour.

Q: While classic Dermatofibrosarcoma Protuberans consists of cytologically uniform spindled cells, regions exhibiting increased atypia and higher proliferative activity indicate [...] transformation.
Dermatofibrosarcoma protuberans. Increased cytological atypia and increased proliferative activity are seen in fibrosarcomatous areas.
A: fibrosarcomatous
Back Extra: Dermatofibrosarcoma Protuberans
- Clinical: Dermatofibrosarcoma protuberans typically presents as a nodular or multinodular cutaneous mass, often with a history of slow but persistent growth. Early lesions may show a plaque-like growth with peripheral red discolouration.
- Micro: Classic DFSP is characterized by a diffuse infiltration of dermis and subcutis, with a honeycomb appearance. The tumour cells are cytologically uniform spindled cells arranged in a storiform pattern.
- Ancillary: Immunohistochemistry shows strong CD34 positivity in tumour cells, which can help differentiate DFSP from other fibroblastic tumours. The detection of the COL1A1-PDGFB fusion is also crucial for diagnosis.
Reference Gallery:
Dermatofibrosarcoma protuberans. Giant dermatofibrosarcoma protuberans presenting clinically as a huge exophytic, multinodular mass with focal ulceration.
Dermatofibrosarcoma protuberans. A case containing numerous blood vessels mimicking a vascular lesion.
Dermatofibrosarcoma protuberans. Increased cytological atypia and increased proliferative activity are seen in fibrosarcomatous areas.
Dermatofibrosarcoma protuberans. Pigmented cells are seen in addition to fibroblastic tumour cells.
Dermatofibrosarcoma protuberans. A diffusely infiltrating myxoid neoplasm with numerous vessels with slightly fibrosed vessel walls is seen.
Dermatofibrosarcoma protuberans. An example with focal myoid differentiation, showing a proliferation of eosinophilic spindled tumour cells set in a hyalinized stroma.
Dermatofibrosarcoma protuberans. Flat, plaque-like dermatofibrosarcoma protuberans mimicking a benign dermal neoplasm.
Dermatofibrosarcoma protuberans. A 4-year-old boy with known adenosine deaminase–deficient severe combined immunodeficiency developed multiple flat dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans. A hypocellular example of flat dermatofibrosarcoma protuberans is seen in this young patient with known adenosine deaminase–deficient severe combined immunodeficiency.
Dermatofibrosarcoma protuberans. The classic G-banded karyotype shows two supernumerary chromosomes (arrows).
Dermatofibrosarcoma protuberans. Multiplexed spectral in situ hybridization of a chromosomal spread shows supernumerary chromosomes pseudocoloured to demonstrate material from both 22 and 17, in pink and blue, respectively (asterisks).
Dermatofibrosarcoma protuberans. Cross-sectioning reveals a firm fibrous tumour.

Q: Histologically, Dermatofibrosarcoma Protuberans deeply infiltrates the subcutaneous fat to create a "honeycomb" appearance, featuring uniform spindled cells arranged in a classic [...] pattern.
Dermatofibrosarcoma protuberans. Flat, plaque-like dermatofibrosarcoma protuberans mimicking a benign dermal neoplasm.
A: storiform
Back Extra: Dermatofibrosarcoma Protuberans
- Clinical: Dermatofibrosarcoma protuberans typically presents as a nodular or multinodular cutaneous mass, often with a history of slow but persistent growth. Early lesions may show a plaque-like growth with peripheral red discolouration.
- Micro: Classic DFSP is characterized by a diffuse infiltration of dermis and subcutis, with a honeycomb appearance. The tumour cells are cytologically uniform spindled cells arranged in a storiform pattern.
- Ancillary: Immunohistochemistry shows strong CD34 positivity in tumour cells, which can help differentiate DFSP from other fibroblastic tumours. The detection of the COL1A1-PDGFB fusion is also crucial for diagnosis.
Reference Gallery:
Dermatofibrosarcoma protuberans. Giant dermatofibrosarcoma protuberans presenting clinically as a huge exophytic, multinodular mass with focal ulceration.
Dermatofibrosarcoma protuberans. A case containing numerous blood vessels mimicking a vascular lesion.
Dermatofibrosarcoma protuberans. Increased cytological atypia and increased proliferative activity are seen in fibrosarcomatous areas.
Dermatofibrosarcoma protuberans. Pigmented cells are seen in addition to fibroblastic tumour cells.
Dermatofibrosarcoma protuberans. A diffusely infiltrating myxoid neoplasm with numerous vessels with slightly fibrosed vessel walls is seen.
Dermatofibrosarcoma protuberans. An example with focal myoid differentiation, showing a proliferation of eosinophilic spindled tumour cells set in a hyalinized stroma.
Dermatofibrosarcoma protuberans. Flat, plaque-like dermatofibrosarcoma protuberans mimicking a benign dermal neoplasm.
Dermatofibrosarcoma protuberans. A 4-year-old boy with known adenosine deaminase–deficient severe combined immunodeficiency developed multiple flat dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans. A hypocellular example of flat dermatofibrosarcoma protuberans is seen in this young patient with known adenosine deaminase–deficient severe combined immunodeficiency.
Dermatofibrosarcoma protuberans. The classic G-banded karyotype shows two supernumerary chromosomes (arrows).
Dermatofibrosarcoma protuberans. Multiplexed spectral in situ hybridization of a chromosomal spread shows supernumerary chromosomes pseudocoloured to demonstrate material from both 22 and 17, in pink and blue, respectively (asterisks).
Dermatofibrosarcoma protuberans. Cross-sectioning reveals a firm fibrous tumour.

Q: Histologically, [...] is characterized by an infiltrative growth pattern featuring long, sweeping fascicles of bland fibroblasts and myofibroblasts lacking significant nuclear atypia.
Desmoid fibromatosis. The fascicles of desmoid fibromatosis are long and sweeping.
Desmoid fibromatosis. High-power examination reveals bland fibroblasts and myofibroblasts without cytological atypia or nuclear hyperchromasia.
A: Desmoid Fibromatosis
Back Extra: Desmoid Fibromatosis
- Clinical: Desmoid fibromatosis generally presents as a painless, deep-seated mass with a fixed nature on physical examination and a propensity for local recurrence.
- Micro: Long, sweeping fascicles of bland fibroblasts and myofibroblasts with infiltration into surrounding tissues and a lack of nuclear atypia or hyperchromasia.
- Ancillary: CTNNB1 mutation analysis is helpful for diagnosis, with most sporadic cases showing mutations in exon 3 at codons 41 or 45.
Reference Gallery:
Desmoid fibromatosis. Low-power examination reveals an infiltrative lesion extending into surrounding adipose tissue with lymphoid aggregates at the advancing edge.
Desmoid fibromatosis. There is infiltration of adjacent skeletal muscle.
Desmoid fibromatosis. Hyalinized area of a desmoid tumour showing gaping thin-walled blood vessels.
Desmoid fibromatosis. Gross examination reveals a firm, tan surface with infiltration into surrounding fat and skeletal muscle.
Desmoid fibromatosis. The fascicles of desmoid fibromatosis are long and sweeping.
Desmoid fibromatosis. High-power examination reveals bland fibroblasts and myofibroblasts without cytological atypia or nuclear hyperchromasia.
Desmoid fibromatosis. Occasionally, desmoid tumours, especially those arising in the abdominal cavity, may show areas with keloid-type collagen deposition.
Desmoid fibromatosis. Axial T2-weighted MRI of the abdomen shows a mass within the rectus abdominis with mixed internal heterogeneity. Areas of low signal (arrow) correspond to fibrosis, whereas areas of high T2 signal (arrowheads) correspond to areas of increased cellularity.

Q: A deep-seated, firm, tan mass aggressively infiltrating the skeletal muscle (e.g., rectus abdominis) with alternating areas of cellularity and fibrosis on MRI is characteristic of [...].
Desmoid fibromatosis. Gross examination reveals a firm, tan surface with infiltration into surrounding fat and skeletal muscle.
Desmoid fibromatosis. Axial T2-weighted MRI of the abdomen shows a mass within the rectus abdominis with mixed internal heterogeneity. Areas of low signal (arrow) correspond to fibrosis, whereas areas of high T2 signal (arrowheads) correspond to areas of increased cellularity.
A: Desmoid Fibromatosis
Back Extra: Desmoid Fibromatosis
- Clinical: Desmoid fibromatosis generally presents as a painless, deep-seated mass with a fixed nature on physical examination and a propensity for local recurrence.
- Micro: Long, sweeping fascicles of bland fibroblasts and myofibroblasts with infiltration into surrounding tissues and a lack of nuclear atypia or hyperchromasia.
- Ancillary: CTNNB1 mutation analysis is helpful for diagnosis, with most sporadic cases showing mutations in exon 3 at codons 41 or 45.
Reference Gallery:
Desmoid fibromatosis. Low-power examination reveals an infiltrative lesion extending into surrounding adipose tissue with lymphoid aggregates at the advancing edge.
Desmoid fibromatosis. There is infiltration of adjacent skeletal muscle.
Desmoid fibromatosis. Hyalinized area of a desmoid tumour showing gaping thin-walled blood vessels.
Desmoid fibromatosis. Gross examination reveals a firm, tan surface with infiltration into surrounding fat and skeletal muscle.
Desmoid fibromatosis. The fascicles of desmoid fibromatosis are long and sweeping.
Desmoid fibromatosis. High-power examination reveals bland fibroblasts and myofibroblasts without cytological atypia or nuclear hyperchromasia.
Desmoid fibromatosis. Occasionally, desmoid tumours, especially those arising in the abdominal cavity, may show areas with keloid-type collagen deposition.
Desmoid fibromatosis. Axial T2-weighted MRI of the abdomen shows a mass within the rectus abdominis with mixed internal heterogeneity. Areas of low signal (arrow) correspond to fibrosis, whereas areas of high T2 signal (arrowheads) correspond to areas of increased cellularity.

Q: While much of the tumor consists of dense cellular fascicles, the more hyalinized areas of Desmoid Fibromatosis characteristically contain thin-walled, [...] blood vessels.
Desmoid fibromatosis. Hyalinized area of a desmoid tumour showing gaping thin-walled blood vessels.
A: gaping
Back Extra: Desmoid Fibromatosis
- Clinical: Desmoid fibromatosis generally presents as a painless, deep-seated mass with a fixed nature on physical examination and a propensity for local recurrence.
- Micro: Long, sweeping fascicles of bland fibroblasts and myofibroblasts with infiltration into surrounding tissues and a lack of nuclear atypia or hyperchromasia.
- Ancillary: CTNNB1 mutation analysis is helpful for diagnosis, with most sporadic cases showing mutations in exon 3 at codons 41 or 45.
Reference Gallery:
Desmoid fibromatosis. Low-power examination reveals an infiltrative lesion extending into surrounding adipose tissue with lymphoid aggregates at the advancing edge.
Desmoid fibromatosis. There is infiltration of adjacent skeletal muscle.
Desmoid fibromatosis. Hyalinized area of a desmoid tumour showing gaping thin-walled blood vessels.
Desmoid fibromatosis. Gross examination reveals a firm, tan surface with infiltration into surrounding fat and skeletal muscle.
Desmoid fibromatosis. The fascicles of desmoid fibromatosis are long and sweeping.
Desmoid fibromatosis. High-power examination reveals bland fibroblasts and myofibroblasts without cytological atypia or nuclear hyperchromasia.
Desmoid fibromatosis. Occasionally, desmoid tumours, especially those arising in the abdominal cavity, may show areas with keloid-type collagen deposition.
Desmoid fibromatosis. Axial T2-weighted MRI of the abdomen shows a mass within the rectus abdominis with mixed internal heterogeneity. Areas of low signal (arrow) correspond to fibrosis, whereas areas of high T2 signal (arrowheads) correspond to areas of increased cellularity.

Q: Histologically, EWSR1-SMAD3-positive fibroblastic tumor typically displays a characteristic zonation pattern featuring a cellular periphery of intersecting spindle cell fascicles and an acellular, [...] center.
EWSR1-SMAD3 fibroblastic tumour. Low-power view showing the characteristic zonation with an acellular hyalinized centre and peripheral areas composed of a cellular spindle cell component. Focal calcifications can also be noted.
EWSR1-SMAD3 fibroblastic tumour. Higher power of the peripheral area showing intersecting fascicles of monomorphic spindle cells with pale eosinophilic cytoplasm and uniform ovoid nuclei.
A: hyalinized
Back Extra: EWSR1-SMAD3-positive fibroblastic tumour
- Clinical: EWSR1-SMAD3-positive fibroblastic tumours typically present as small, painless, superficial lesions in acral sites, with a wide age range and female predilection.
- Micro: The tumours are well-demarcated with an acellular, hyalinized centre and peripheral areas of intersecting cellular fascicles of spindle cells. Focal calcifications may be present.
- Ancillary: The diagnosis is confirmed by the presence of the EWSR1-SMAD3 fusion, which can be detected by molecular methods, and diffuse nuclear staining for ERG by immunohistochemistry.
Reference Gallery:
EWSR1-SMAD3 fibroblastic tumour. Low-power view showing the characteristic zonation with an acellular hyalinized centre and peripheral areas composed of a cellular spindle cell component. Focal calcifications can also be noted.
EWSR1-SMAD3 fibroblastic tumour. Higher power of the peripheral area showing intersecting fascicles of monomorphic spindle cells with pale eosinophilic cytoplasm and uniform ovoid nuclei.
EWSR1-SMAD3 fibroblastic tumour. Diffuse nuclear staining for ERG by immunohistochemistry.
EWSR1-SMAD3 fibroblastic tumour. Diagrammatic representation of the EWSR1-SMAD3 fusion and the predicted protein domains of the fusion oncoprotein.

Q: By immunohistochemistry, EWSR1-SMAD3-positive fibroblastic tumor characteristically shows diffuse nuclear positivity for [...].
EWSR1-SMAD3 fibroblastic tumour. Diffuse nuclear staining for ERG by immunohistochemistry.
A: ERG
Back Extra: EWSR1-SMAD3-positive fibroblastic tumour
- Clinical: EWSR1-SMAD3-positive fibroblastic tumours typically present as small, painless, superficial lesions in acral sites, with a wide age range and female predilection.
- Micro: The tumours are well-demarcated with an acellular, hyalinized centre and peripheral areas of intersecting cellular fascicles of spindle cells. Focal calcifications may be present.
- Ancillary: The diagnosis is confirmed by the presence of the EWSR1-SMAD3 fusion, which can be detected by molecular methods, and diffuse nuclear staining for ERG by immunohistochemistry.
Reference Gallery:
EWSR1-SMAD3 fibroblastic tumour. Low-power view showing the characteristic zonation with an acellular hyalinized centre and peripheral areas composed of a cellular spindle cell component. Focal calcifications can also be noted.
EWSR1-SMAD3 fibroblastic tumour. Higher power of the peripheral area showing intersecting fascicles of monomorphic spindle cells with pale eosinophilic cytoplasm and uniform ovoid nuclei.
EWSR1-SMAD3 fibroblastic tumour. Diffuse nuclear staining for ERG by immunohistochemistry.
EWSR1-SMAD3 fibroblastic tumour. Diagrammatic representation of the EWSR1-SMAD3 fusion and the predicted protein domains of the fusion oncoprotein.

Q: Microscopically, Giant Cell Fibroblastoma is characterized by hypocellular areas containing spindle cells and multinucleated giant cells that typically line irregularly branching [...].
Giant cell fibroblastoma. Low-power view shows a hypocellular dermal neoplasm with irregularly branching pseudovascular spaces.
Giant cell fibroblastoma. The neoplasms are composed of spindle cells and scattered multinucleated giant cells that also line pseudovascular spaces.
A: pseudovascular spaces
Back Extra: Giant Cell Fibroblastoma
- Clinical: Giant cell fibroblastoma is a rare neoplasm that primarily affects children, with a mean age of 6 years and a male predominance. It presents as a slow-growing, painless cutaneous lesion, most often plaque-like, and is found predominantly in the trunk, groin, and axillary regions.
- Micro: The tumor is characterized by hypocellular areas with myxoid or collagenous stroma, spindle and stellate cells, and multinucleated giant cells lining irregularly branching pseudovascular spaces. Mitoses are rare, and tumor necrosis is uncommon.
- Ancillary: The COL1A1-PDGFB fusion can be detected by molecular methods, but it is not generally required for diagnosis.
Reference Gallery:
Giant cell fibroblastoma. Low-power view shows a hypocellular dermal neoplasm with irregularly branching pseudovascular spaces.
Giant cell fibroblastoma. The neoplasms are composed of spindle cells and scattered multinucleated giant cells that also line pseudovascular spaces.
Giant cell fibroblastoma. Hybrid tumour with features of giant cell fibroblastoma (top) and dermatofibrosarcoma protuberans (bottom).

Q: Giant Cell Fibroblastoma may occasionally present as a hybrid tumor demonstrating admixed areas of classic morphology alongside typical features of [...].
Giant cell fibroblastoma. Hybrid tumour with features of giant cell fibroblastoma (top) and dermatofibrosarcoma protuberans (bottom).
A: dermatofibrosarcoma protuberans (DFSP)
Back Extra: Giant Cell Fibroblastoma
- Clinical: Giant cell fibroblastoma is a rare neoplasm that primarily affects children, with a mean age of 6 years and a male predominance. It presents as a slow-growing, painless cutaneous lesion, most often plaque-like, and is found predominantly in the trunk, groin, and axillary regions.
- Micro: The tumor is characterized by hypocellular areas with myxoid or collagenous stroma, spindle and stellate cells, and multinucleated giant cells lining irregularly branching pseudovascular spaces. Mitoses are rare, and tumor necrosis is uncommon.
- Ancillary: The COL1A1-PDGFB fusion can be detected by molecular methods, but it is not generally required for diagnosis.
Reference Gallery:
Giant cell fibroblastoma. Low-power view shows a hypocellular dermal neoplasm with irregularly branching pseudovascular spaces.
Giant cell fibroblastoma. The neoplasms are composed of spindle cells and scattered multinucleated giant cells that also line pseudovascular spaces.
Giant cell fibroblastoma. Hybrid tumour with features of giant cell fibroblastoma (top) and dermatofibrosarcoma protuberans (bottom).

Q: Presenting typically at birth or detected on prenatal ultrasound, [...] is characterized clinically as a rapidly enlarging, painless soft tissue mass often arising on the extremities.
Infantile fibrosarcoma. Clinical photograph. Large soft tissue forearm mass.
A: Infantile Fibrosarcoma
Back Extra: Infantile Fibrosarcoma
- Clinical: Infantile fibrosarcoma (IFS) typically presents as a localized, rapidly enlarging, painless mass or swelling, often found at birth or detected on prenatal ultrasound.
- Micro: Histologically, IFS is characterized by a cellular neoplasm composed of monomorphic spindled to ovoid cells with scant cytoplasm, arranged in randomly oriented compact sheets or herringbone fascicles, and often a myxoid background stroma.
- Ancillary: Most cases of IFS harbour the canonical ETV6-NTRK3 fusion, which can be detected by immunohistochemistry using a pan-TRK antibody.
Reference Gallery:
Infantile fibrosarcoma. Clinical photograph. Large soft tissue forearm mass.
Infantile fibrosarcoma. Primitive stellate cells in a predominantly myxoid stroma (with ETV6-NTRK3 fusion).
Infantile fibrosarcoma. Poorly formed fascicular growth pattern (with LMNA-NTRK1 fusion).
Infantile fibrosarcoma. Cellular ovoid to round cell pattern (with ETV6-NTRK3 fusion).
Infantile fibrosarcoma. Immunohistochemistry with pan-TRK antibody. Nuclear expression in a tumour with ETV6-NTRK3 fusion.
Infantile fibrosarcoma. Immunohistochemistry with pan-TRK antibody. Cytoplasmic expression in a tumour with TPM3-NTRK1 fusion.
Infantile fibrosarcoma. Long intersecting fascicles or herringbone pattern of growth (with TPR-NTRK1 fusion).
Infantile fibrosarcoma. Low-magnification view of infantile fibrosarcoma with numerous dilated, irregularly branching blood vessels (with ETV6-NTRK3 fusion).

Q: Microscopically, Infantile Fibrosarcoma is composed of monomorphic spindled cells frequently arranged in intersecting fascicles, creating a classic [...] growth pattern.
Infantile fibrosarcoma. Long intersecting fascicles or herringbone pattern of growth (with TPR-NTRK1 fusion).
A: herringbone
Back Extra: Infantile Fibrosarcoma
- Clinical: Infantile fibrosarcoma (IFS) typically presents as a localized, rapidly enlarging, painless mass or swelling, often found at birth or detected on prenatal ultrasound.
- Micro: Histologically, IFS is characterized by a cellular neoplasm composed of monomorphic spindled to ovoid cells with scant cytoplasm, arranged in randomly oriented compact sheets or herringbone fascicles, and often a myxoid background stroma.
- Ancillary: Most cases of IFS harbour the canonical ETV6-NTRK3 fusion, which can be detected by immunohistochemistry using a pan-TRK antibody.
Reference Gallery:
Infantile fibrosarcoma. Clinical photograph. Large soft tissue forearm mass.
Infantile fibrosarcoma. Primitive stellate cells in a predominantly myxoid stroma (with ETV6-NTRK3 fusion).
Infantile fibrosarcoma. Poorly formed fascicular growth pattern (with LMNA-NTRK1 fusion).
Infantile fibrosarcoma. Cellular ovoid to round cell pattern (with ETV6-NTRK3 fusion).
Infantile fibrosarcoma. Immunohistochemistry with pan-TRK antibody. Nuclear expression in a tumour with ETV6-NTRK3 fusion.
Infantile fibrosarcoma. Immunohistochemistry with pan-TRK antibody. Cytoplasmic expression in a tumour with TPM3-NTRK1 fusion.
Infantile fibrosarcoma. Long intersecting fascicles or herringbone pattern of growth (with TPR-NTRK1 fusion).
Infantile fibrosarcoma. Low-magnification view of infantile fibrosarcoma with numerous dilated, irregularly branching blood vessels (with ETV6-NTRK3 fusion).

Q: Most cases of Infantile Fibrosarcoma harbor a canonical ETV6-NTRK3 gene fusion, which can be identified via immunohistochemistry using a [...] antibody.
Infantile fibrosarcoma. Immunohistochemistry with pan-TRK antibody. Nuclear expression in a tumour with ETV6-NTRK3 fusion.
Infantile fibrosarcoma. Immunohistochemistry with pan-TRK antibody. Cytoplasmic expression in a tumour with TPM3-NTRK1 fusion.
A: pan-TRK
Back Extra: Infantile Fibrosarcoma
- Clinical: Infantile fibrosarcoma (IFS) typically presents as a localized, rapidly enlarging, painless mass or swelling, often found at birth or detected on prenatal ultrasound.
- Micro: Histologically, IFS is characterized by a cellular neoplasm composed of monomorphic spindled to ovoid cells with scant cytoplasm, arranged in randomly oriented compact sheets or herringbone fascicles, and often a myxoid background stroma.
- Ancillary: Most cases of IFS harbour the canonical ETV6-NTRK3 fusion, which can be detected by immunohistochemistry using a pan-TRK antibody.
Reference Gallery:
Infantile fibrosarcoma. Clinical photograph. Large soft tissue forearm mass.
Infantile fibrosarcoma. Primitive stellate cells in a predominantly myxoid stroma (with ETV6-NTRK3 fusion).
Infantile fibrosarcoma. Poorly formed fascicular growth pattern (with LMNA-NTRK1 fusion).
Infantile fibrosarcoma. Cellular ovoid to round cell pattern (with ETV6-NTRK3 fusion).
Infantile fibrosarcoma. Immunohistochemistry with pan-TRK antibody. Nuclear expression in a tumour with ETV6-NTRK3 fusion.
Infantile fibrosarcoma. Immunohistochemistry with pan-TRK antibody. Cytoplasmic expression in a tumour with TPM3-NTRK1 fusion.
Infantile fibrosarcoma. Long intersecting fascicles or herringbone pattern of growth (with TPR-NTRK1 fusion).
Infantile fibrosarcoma. Low-magnification view of infantile fibrosarcoma with numerous dilated, irregularly branching blood vessels (with ETV6-NTRK3 fusion).

Q: Histologically, Inflammatory Myofibroblastic Tumor exhibits myxoid, hypercellular, and hypocellular fibrous patterns, often containing characteristic [...] cells with large rounded nuclei and prominent nucleoli.
Inflammatory myofibroblastic tumour. The hypercellular pattern shows a fascicular spindle cell proliferation intermingled with inflammatory cells.
Inflammatory myofibroblastic tumour. Ganglion-like polygonal cells show large rounded nuclei and prominent nucleoli.
A: ganglion-like
Back Extra: Inflammatory Myofibroblastic Tumor
- Clinical: Inflammatory Myofibroblastic Tumor (IMT) often presents with symptoms based on its location, such as gastrointestinal obstruction or bleeding for abdominal tumours, and chest pain and dyspnoea for pulmonary IMT. Up to one-third of patients may have a systemic inflammatory syndrome with fever, malaise, weight loss, and laboratory abnormalities like microcytic hypochromic anaemia and elevated ESR.
- Micro: IMT can exhibit three main histological patterns: myxoid (loosely arranged plump or spindled myofibroblasts in a myxoid background with inflammatory cells), hypercellular (compact fascicular spindle cell proliferation with inflammatory infiltrate), and hypocellular fibrous (hyalinized collagenous stroma with sparse inflammatory cells). Ganglion-like cells and eosinophilic cytoplasm are characteristic features.
- Ancillary: Immunohistochemistry (IHC) often shows variable staining for SMA, MSA, calponin, and desmin. ALK immunoreactivity is present in 50-60% of cases, correlating with ALK gene rearrangements. Molecular studies reveal ALK rearrangements in 50-60% of IMTs, particularly in children and young adults, with partners such as TPM3, TPM4, and CLTC.
Reference Gallery:
Inflammatory myofibroblastic tumour. The myxoid pattern displays spindled myofibroblasts dispersed in a myxoid background with lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour. The hypercellular pattern shows a fascicular spindle cell proliferation intermingled with inflammatory cells.
Inflammatory myofibroblastic tumour. The hypocellular fibrous pattern is characterized by hyalinized collagenous stroma with sparse spindle cells and lymphoplasmacytic inflammation. Focal calcification is noted.
Inflammatory myofibroblastic tumour. The spindled myofibroblasts show vesicular nuclei, small nucleoli, and eosinophilic cytoplasm.
Inflammatory myofibroblastic tumour. Ganglion-like polygonal cells show large rounded nuclei and prominent nucleoli.
Epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK rearrangement. Plump polygonal and epithelioid tumour cells with prominent nucleoli are characteristic. The neutrophilic infiltration seen here is often present.
Epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK rearrangement. Distinctive nuclear membranous immunoreactivity for ALK is seen.
Inflammatory myofibroblastic tumour with TPM3-ALK gene fusion. Diffuse cytoplasmic staining for ALK is seen.
Inflammatory myofibroblastic tumour. The tumour presented as a circumscribed, solid mass in the lung.
Inflammatory myofibroblastic tumour karyotypes. A Left to right: the 2;17 translocation resulting in CLTC-ALK fusion (schematic and partial G-banded karyotype) with corresponding ALK breakpoint-spanning probe FISH demonstrating a signal split; the white arrow indicates der(2) and the yellow arrow der(17). ALK granular cytoplasmic immunostaining is seen with CLTC partnership; CLTC encodes a protein component of the cytoplasmic face of intracellular organelles (coated vesicles and coated pits). B Left to right: schematic, partial G-banded karyotype and differentially labelled, dual-spanning RANBP2 and ALK FISH illustrating the RANBP2-ALK fusion; both chromosome 2 homologues involved in the translocation in this fusion example and juxtaposed orange/green signals indicate fusion (white arrows). Nuclear membrane ALK immunostaining is featured when the ALK fusion partner is RANBP2, because RANBP2 encodes a large nucleopore protein localized at the cytoplasmic side of the nuclear pore complex.

Q: Approximately 50-60% of cases of Inflammatory Myofibroblastic Tumor, particularly in children and young adults, harbor a gene rearrangement involving [...].
Inflammatory myofibroblastic tumour with TPM3-ALK gene fusion. Diffuse cytoplasmic staining for ALK is seen.
Inflammatory myofibroblastic tumour karyotypes. A Left to right: the 2;17 translocation resulting in CLTC-ALK fusion (schematic and partial G-banded karyotype) with corresponding ALK breakpoint-spanning probe FISH demonstrating a signal split; the white arrow indicates der(2) and the yellow arrow der(17). ALK granular cytoplasmic immunostaining is seen with CLTC partnership; CLTC encodes a protein component of the cytoplasmic face of intracellular organelles (coated vesicles and coated pits). B Left to right: schematic, partial G-banded karyotype and differentially labelled, dual-spanning RANBP2 and ALK FISH illustrating the RANBP2-ALK fusion; both chromosome 2 homologues involved in the translocation in this fusion example and juxtaposed orange/green signals indicate fusion (white arrows). Nuclear membrane ALK immunostaining is featured when the ALK fusion partner is RANBP2, because RANBP2 encodes a large nucleopore protein localized at the cytoplasmic side of the nuclear pore complex.
A: ALK
Back Extra: Inflammatory Myofibroblastic Tumor
- Clinical: Inflammatory Myofibroblastic Tumor (IMT) often presents with symptoms based on its location, such as gastrointestinal obstruction or bleeding for abdominal tumours, and chest pain and dyspnoea for pulmonary IMT. Up to one-third of patients may have a systemic inflammatory syndrome with fever, malaise, weight loss, and laboratory abnormalities like microcytic hypochromic anaemia and elevated ESR.
- Micro: IMT can exhibit three main histological patterns: myxoid (loosely arranged plump or spindled myofibroblasts in a myxoid background with inflammatory cells), hypercellular (compact fascicular spindle cell proliferation with inflammatory infiltrate), and hypocellular fibrous (hyalinized collagenous stroma with sparse inflammatory cells). Ganglion-like cells and eosinophilic cytoplasm are characteristic features.
- Ancillary: Immunohistochemistry (IHC) often shows variable staining for SMA, MSA, calponin, and desmin. ALK immunoreactivity is present in 50-60% of cases, correlating with ALK gene rearrangements. Molecular studies reveal ALK rearrangements in 50-60% of IMTs, particularly in children and young adults, with partners such as TPM3, TPM4, and CLTC.
Reference Gallery:
Inflammatory myofibroblastic tumour. The myxoid pattern displays spindled myofibroblasts dispersed in a myxoid background with lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour. The hypercellular pattern shows a fascicular spindle cell proliferation intermingled with inflammatory cells.
Inflammatory myofibroblastic tumour. The hypocellular fibrous pattern is characterized by hyalinized collagenous stroma with sparse spindle cells and lymphoplasmacytic inflammation. Focal calcification is noted.
Inflammatory myofibroblastic tumour. The spindled myofibroblasts show vesicular nuclei, small nucleoli, and eosinophilic cytoplasm.
Inflammatory myofibroblastic tumour. Ganglion-like polygonal cells show large rounded nuclei and prominent nucleoli.
Epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK rearrangement. Plump polygonal and epithelioid tumour cells with prominent nucleoli are characteristic. The neutrophilic infiltration seen here is often present.
Epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK rearrangement. Distinctive nuclear membranous immunoreactivity for ALK is seen.
Inflammatory myofibroblastic tumour with TPM3-ALK gene fusion. Diffuse cytoplasmic staining for ALK is seen.
Inflammatory myofibroblastic tumour. The tumour presented as a circumscribed, solid mass in the lung.
Inflammatory myofibroblastic tumour karyotypes. A Left to right: the 2;17 translocation resulting in CLTC-ALK fusion (schematic and partial G-banded karyotype) with corresponding ALK breakpoint-spanning probe FISH demonstrating a signal split; the white arrow indicates der(2) and the yellow arrow der(17). ALK granular cytoplasmic immunostaining is seen with CLTC partnership; CLTC encodes a protein component of the cytoplasmic face of intracellular organelles (coated vesicles and coated pits). B Left to right: schematic, partial G-banded karyotype and differentially labelled, dual-spanning RANBP2 and ALK FISH illustrating the RANBP2-ALK fusion; both chromosome 2 homologues involved in the translocation in this fusion example and juxtaposed orange/green signals indicate fusion (white arrows). Nuclear membrane ALK immunostaining is featured when the ALK fusion partner is RANBP2, because RANBP2 encodes a large nucleopore protein localized at the cytoplasmic side of the nuclear pore complex.

Q: The epithelioid variant of Inflammatory Myofibroblastic Tumor often presents with a prominent neutrophilic infiltrate and is characteristically driven by a [...]-ALK gene fusion, which uniquely yields a nuclear membranous pattern on immunohistochemistry.
Epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK rearrangement. Plump polygonal and epithelioid tumour cells with prominent nucleoli are characteristic. The neutrophilic infiltration seen here is often present.
Epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK rearrangement. Distinctive nuclear membranous immunoreactivity for ALK is seen.
A: RANBP2
Back Extra: Inflammatory Myofibroblastic Tumor
- Clinical: Inflammatory Myofibroblastic Tumor (IMT) often presents with symptoms based on its location, such as gastrointestinal obstruction or bleeding for abdominal tumours, and chest pain and dyspnoea for pulmonary IMT. Up to one-third of patients may have a systemic inflammatory syndrome with fever, malaise, weight loss, and laboratory abnormalities like microcytic hypochromic anaemia and elevated ESR.
- Micro: IMT can exhibit three main histological patterns: myxoid (loosely arranged plump or spindled myofibroblasts in a myxoid background with inflammatory cells), hypercellular (compact fascicular spindle cell proliferation with inflammatory infiltrate), and hypocellular fibrous (hyalinized collagenous stroma with sparse inflammatory cells). Ganglion-like cells and eosinophilic cytoplasm are characteristic features.
- Ancillary: Immunohistochemistry (IHC) often shows variable staining for SMA, MSA, calponin, and desmin. ALK immunoreactivity is present in 50-60% of cases, correlating with ALK gene rearrangements. Molecular studies reveal ALK rearrangements in 50-60% of IMTs, particularly in children and young adults, with partners such as TPM3, TPM4, and CLTC.
Reference Gallery:
Inflammatory myofibroblastic tumour. The myxoid pattern displays spindled myofibroblasts dispersed in a myxoid background with lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour. The hypercellular pattern shows a fascicular spindle cell proliferation intermingled with inflammatory cells.
Inflammatory myofibroblastic tumour. The hypocellular fibrous pattern is characterized by hyalinized collagenous stroma with sparse spindle cells and lymphoplasmacytic inflammation. Focal calcification is noted.
Inflammatory myofibroblastic tumour. The spindled myofibroblasts show vesicular nuclei, small nucleoli, and eosinophilic cytoplasm.
Inflammatory myofibroblastic tumour. Ganglion-like polygonal cells show large rounded nuclei and prominent nucleoli.
Epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK rearrangement. Plump polygonal and epithelioid tumour cells with prominent nucleoli are characteristic. The neutrophilic infiltration seen here is often present.
Epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK rearrangement. Distinctive nuclear membranous immunoreactivity for ALK is seen.
Inflammatory myofibroblastic tumour with TPM3-ALK gene fusion. Diffuse cytoplasmic staining for ALK is seen.
Inflammatory myofibroblastic tumour. The tumour presented as a circumscribed, solid mass in the lung.
Inflammatory myofibroblastic tumour karyotypes. A Left to right: the 2;17 translocation resulting in CLTC-ALK fusion (schematic and partial G-banded karyotype) with corresponding ALK breakpoint-spanning probe FISH demonstrating a signal split; the white arrow indicates der(2) and the yellow arrow der(17). ALK granular cytoplasmic immunostaining is seen with CLTC partnership; CLTC encodes a protein component of the cytoplasmic face of intracellular organelles (coated vesicles and coated pits). B Left to right: schematic, partial G-banded karyotype and differentially labelled, dual-spanning RANBP2 and ALK FISH illustrating the RANBP2-ALK fusion; both chromosome 2 homologues involved in the translocation in this fusion example and juxtaposed orange/green signals indicate fusion (white arrows). Nuclear membrane ALK immunostaining is featured when the ALK fusion partner is RANBP2, because RANBP2 encodes a large nucleopore protein localized at the cytoplasmic side of the nuclear pore complex.

Q: The characteristic histologic presentation of [...] is a poorly demarcated pediatric tumor composed of mature adipose tissue traversed by cellular fascicles of bland spindle cells.
Lipofibromatosis. The tumour, involving subcutaneous fat and skeletal muscle, is composed of mature-appearing adipose tissue and cellular fibrous septa without atypia or mitotic activity, imparting a fibromatosis-like appearance.
Lipofibromatosis. The fibroblasts show a uniform appearance and are embedded in an abundant collagenous matrix.
A: Lipofibromatosis
Back Extra: Lipofibromatosis
- Clinical: Lipofibromatosis typically presents as a slow-growing, poorly demarcated subcutaneous mass in children, with a predilection for the hands and feet.
- Micro: The lesion is composed of mature adipose tissue traversed by cellular fascicles of spindle cells with bland, uniform, elongated nuclei.
- Ancillary: Identification of fusions involving ligands to EGFR or other receptor tyrosine kinases suggests activation of the PI3K/AKT/mTOR pathway in lipofibromatosis.
Reference Gallery:
Lipofibromatosis. The tumour, involving subcutaneous fat and skeletal muscle, is composed of mature-appearing adipose tissue and cellular fibrous septa without atypia or mitotic activity, imparting a fibromatosis-like appearance.
Lipofibromatosis. The fibroblasts show a uniform appearance and are embedded in an abundant collagenous matrix.

Q: Ancillary testing in Lipofibromatosis often reveals fusions involving ligands to [...] or other receptor tyrosine kinases, which suggests activation of the PI3K/AKT/mTOR pathway.
Lipofibromatosis. The tumour, involving subcutaneous fat and skeletal muscle, is composed of mature-appearing adipose tissue and cellular fibrous septa without atypia or mitotic activity, imparting a fibromatosis-like appearance.
A: EGFR
Back Extra: Lipofibromatosis
- Clinical: Lipofibromatosis typically presents as a slow-growing, poorly demarcated subcutaneous mass in children, with a predilection for the hands and feet.
- Micro: The lesion is composed of mature adipose tissue traversed by cellular fascicles of spindle cells with bland, uniform, elongated nuclei.
- Ancillary: Identification of fusions involving ligands to EGFR or other receptor tyrosine kinases suggests activation of the PI3K/AKT/mTOR pathway in lipofibromatosis.
Reference Gallery:
Lipofibromatosis. The tumour, involving subcutaneous fat and skeletal muscle, is composed of mature-appearing adipose tissue and cellular fibrous septa without atypia or mitotic activity, imparting a fibromatosis-like appearance.
Lipofibromatosis. The fibroblasts show a uniform appearance and are embedded in an abundant collagenous matrix.

Q: A painless, enlarging mass in the head and neck region that demonstrates a diffusely infiltrative growth pattern of spindle-shaped tumor cells with enlarged hyperchromatic nuclei arranged in fascicles is characteristic of [...].
Low-grade myofibroblastic sarcoma. Diffuse infiltration of skeletal muscle by a cellular spindle cell neoplasm.
Low-grade myofibroblastic sarcoma. Some tumours contain more-abundant, palely eosinophilic cytoplasm. Note enlarged, hyperchromatic nuclei and scattered mitotic figures.
Low-grade myofibroblastic sarcoma. The neoplasm is composed of enlarged spindled tumour cells arranged in cellular bundles and fascicles.
A: Low-grade myofibroblastic sarcoma
Back Extra: Low-grade myofibroblastic sarcoma
- Clinical: Most patients with low-grade myofibroblastic sarcoma present with a painless swelling or an enlarging mass, often in the head and neck region.
- Micro: Histologically, the neoplasm shows a diffusely infiltrative growth pattern with spindle-shaped tumour cells, enlarged hyperchromatic nuclei, and moderate nuclear atypia.
- Ancillary: Immunohistochemistry reveals variable positivity for SMA and/or desmin, and a subset of cases show nuclear β-catenin staining.
Reference Gallery:
Low-grade myofibroblastic sarcoma. Diffuse infiltration of skeletal muscle by a cellular spindle cell neoplasm.
Low-grade myofibroblastic sarcoma. Some tumours contain more-abundant, palely eosinophilic cytoplasm. Note enlarged, hyperchromatic nuclei and scattered mitotic figures.
Low-grade myofibroblastic sarcoma. Tumour cells are often positive for desmin.
Low-grade myofibroblastic sarcoma. The neoplasm is composed of enlarged spindled tumour cells arranged in cellular bundles and fascicles.

Q: In Low-grade myofibroblastic sarcoma, immunohistochemistry typically reveals variable positivity for SMA and/or [...], confirming myofibroblastic differentiation.
Low-grade myofibroblastic sarcoma. Tumour cells are often positive for desmin.
A: desmin
Back Extra: Low-grade myofibroblastic sarcoma
- Clinical: Most patients with low-grade myofibroblastic sarcoma present with a painless swelling or an enlarging mass, often in the head and neck region.
- Micro: Histologically, the neoplasm shows a diffusely infiltrative growth pattern with spindle-shaped tumour cells, enlarged hyperchromatic nuclei, and moderate nuclear atypia.
- Ancillary: Immunohistochemistry reveals variable positivity for SMA and/or desmin, and a subset of cases show nuclear β-catenin staining.
Reference Gallery:
Low-grade myofibroblastic sarcoma. Diffuse infiltration of skeletal muscle by a cellular spindle cell neoplasm.
Low-grade myofibroblastic sarcoma. Some tumours contain more-abundant, palely eosinophilic cytoplasm. Note enlarged, hyperchromatic nuclei and scattered mitotic figures.
Low-grade myofibroblastic sarcoma. Tumour cells are often positive for desmin.
Low-grade myofibroblastic sarcoma. The neoplasm is composed of enlarged spindled tumour cells arranged in cellular bundles and fascicles.

Q: A characteristic molecular alteration in Myxoinflammatory Fibroblastic Sarcoma is the amplification of the [...] gene.
Myxoinflammatory fibroblastic sarcoma. Multiple green signals depict the VGLL3 amplification at 3p12.1; the red signal is the reference probe on 3q12.1-q12.2.
A: VGLL3
Back Extra: Myxoinflammatory Fibroblastic Sarcoma
- Clinical: Myxoinflammatory fibroblastic sarcoma typically presents as solitary, painless masses in the distal extremities, often measuring about 3 cm.
- Micro: Histologically, it is characterized by dense inflammation, myxoid to hyalinized stroma, and sheets of epithelioid and spindled cells with large vesicular nuclei and macronucleoli.
- Ancillary: A common genetic event in Myxoinflammatory fibroblastic sarcoma is the amplification of the VGLL3 gene at 3p11.1-p12.1.
Reference Gallery:
Myxoinflammatory fibroblastic sarcoma. These tumours most commonly arise in the subcutaneous tissue of the distal extremities. In this image, the lesion is seen in the adipose tissue at the bottom of the image. Note the lymphoid aggregate in the deep dermis.
Myxoinflammatory fibroblastic sarcoma. Note the binucleated cell in the centre of the field, with macronucleoli.
Myxoinflammatory fibroblastic sarcoma. The cell in the centre is reminiscent of a Hodgkin cell. The presence of the eosinophil beneath it and scattered lymphocytes adds to the mimicry.
Myxoinflammatory fibroblastic sarcoma. This example shows haemosiderin and scattered large cells with macronucleoli.
Myxoinflammatory fibroblastic sarcoma. Multiple green signals depict the VGLL3 amplification at 3p12.1; the red signal is the reference probe on 3q12.1-q12.2.
Myxoinflammatory fibroblastic sarcoma. In some examples, the atypical cells are more numerous. Note the macronucleoli. This case showed a BRAF fusion.
Myxoinflammatory fibroblastic sarcoma. Note the myxoid background, scattered inflammation, and spindle cells in this BRAF-mutated case.

Q: Microscopically, Myxoinflammatory Fibroblastic Sarcoma features a prominent inflammatory infiltrate and large, atypical cells with massive nucleoli that strongly resemble [...] cells.
Myxoinflammatory fibroblastic sarcoma. Note the binucleated cell in the centre of the field, with macronucleoli.
Myxoinflammatory fibroblastic sarcoma. The cell in the centre is reminiscent of a Hodgkin cell. The presence of the eosinophil beneath it and scattered lymphocytes adds to the mimicry.
A: Hodgkin
Back Extra: Myxoinflammatory Fibroblastic Sarcoma
- Clinical: Myxoinflammatory fibroblastic sarcoma typically presents as solitary, painless masses in the distal extremities, often measuring about 3 cm.
- Micro: Histologically, it is characterized by dense inflammation, myxoid to hyalinized stroma, and sheets of epithelioid and spindled cells with large vesicular nuclei and macronucleoli.
- Ancillary: A common genetic event in Myxoinflammatory fibroblastic sarcoma is the amplification of the VGLL3 gene at 3p11.1-p12.1.
Reference Gallery:
Myxoinflammatory fibroblastic sarcoma. These tumours most commonly arise in the subcutaneous tissue of the distal extremities. In this image, the lesion is seen in the adipose tissue at the bottom of the image. Note the lymphoid aggregate in the deep dermis.
Myxoinflammatory fibroblastic sarcoma. Note the binucleated cell in the centre of the field, with macronucleoli.
Myxoinflammatory fibroblastic sarcoma. The cell in the centre is reminiscent of a Hodgkin cell. The presence of the eosinophil beneath it and scattered lymphocytes adds to the mimicry.
Myxoinflammatory fibroblastic sarcoma. This example shows haemosiderin and scattered large cells with macronucleoli.
Myxoinflammatory fibroblastic sarcoma. Multiple green signals depict the VGLL3 amplification at 3p12.1; the red signal is the reference probe on 3q12.1-q12.2.
Myxoinflammatory fibroblastic sarcoma. In some examples, the atypical cells are more numerous. Note the macronucleoli. This case showed a BRAF fusion.
Myxoinflammatory fibroblastic sarcoma. Note the myxoid background, scattered inflammation, and spindle cells in this BRAF-mutated case.

Q: Histologically, Palmar and Plantar Fibromatosis characteristically exhibits a [...] growth pattern of bland, proliferative spindle cells that expand the native fascial or aponeurotic tissue.
Plantar fibromatosis. Low-power view showing typically multinodular growth pattern (within tendoaponeurotic fibrous tissue), as is usually seen in plantar lesions.
Palmar fibromatosis. In the early (proliferative) phase, palmar fascial or aponeurotic tissue is expanded by hypercellular spindle cell nodules.
A: multinodular
Back Extra: Palmar and Plantar Fibromatosis
- Clinical: Palmar and Plantar Fibromatosis typically presents as painless nodules in the hands and feet, often leading to contractures and affecting adults, with a male predominance in palmar cases.
- Micro: Histologically, these lesions are characterized by proliferative phases with cellular spindle cell nodules and a collagenous stroma, with minimal atypia and rare mitotic figures.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Palmar and Plantar Fibromatosis.
Reference Gallery:
Plantar fibromatosis. Intimate association of the cellular, proliferative-phase lesional spindle cells with native fibrotendinous tissue is seen.
Plantar fibromatosis. Spindle cells arranged in long, parallel fascicles in more-densely collagenous matrix. The cells are uniform and lack discernible atypia. There are associated mild chronic inflammation and rare mitotic figures.
Plantar fibromatosis. In the proliferative phase, plump, bland-appearing spindle cells with elongated nuclei with vesicular chromatin and inconspicuous nucleoli are predominant.
Plantar fibromatosis. This lesion shows small numbers of osteoclast-type, multinucleated giant cells, interspersed among the plump, cellular fibroblastic cells.
Palmar fibromatosis. This early-stage lesion is cellular and shows loose fascicles of uniform spindle cells within prominent collagenous stroma.
Plantar fibromatosis. Low-power view showing typically multinodular growth pattern (within tendoaponeurotic fibrous tissue), as is usually seen in plantar lesions.
Palmar fibromatosis. In the early (proliferative) phase, palmar fascial or aponeurotic tissue is expanded by hypercellular spindle cell nodules.

Q: The proliferative phase of Palmar and Plantar Fibromatosis is microscopically characterized by uniform [...] arranged in long, parallel fascicles within a dense collagenous matrix, lacking discernible atypia.
Plantar fibromatosis. Spindle cells arranged in long, parallel fascicles in more-densely collagenous matrix. The cells are uniform and lack discernible atypia. There are associated mild chronic inflammation and rare mitotic figures.
Palmar fibromatosis. This early-stage lesion is cellular and shows loose fascicles of uniform spindle cells within prominent collagenous stroma.
A: spindle cells
Back Extra: Palmar and Plantar Fibromatosis
- Clinical: Palmar and Plantar Fibromatosis typically presents as painless nodules in the hands and feet, often leading to contractures and affecting adults, with a male predominance in palmar cases.
- Micro: Histologically, these lesions are characterized by proliferative phases with cellular spindle cell nodules and a collagenous stroma, with minimal atypia and rare mitotic figures.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Palmar and Plantar Fibromatosis.
Reference Gallery:
Plantar fibromatosis. Intimate association of the cellular, proliferative-phase lesional spindle cells with native fibrotendinous tissue is seen.
Plantar fibromatosis. Spindle cells arranged in long, parallel fascicles in more-densely collagenous matrix. The cells are uniform and lack discernible atypia. There are associated mild chronic inflammation and rare mitotic figures.
Plantar fibromatosis. In the proliferative phase, plump, bland-appearing spindle cells with elongated nuclei with vesicular chromatin and inconspicuous nucleoli are predominant.
Plantar fibromatosis. This lesion shows small numbers of osteoclast-type, multinucleated giant cells, interspersed among the plump, cellular fibroblastic cells.
Palmar fibromatosis. This early-stage lesion is cellular and shows loose fascicles of uniform spindle cells within prominent collagenous stroma.
Plantar fibromatosis. Low-power view showing typically multinodular growth pattern (within tendoaponeurotic fibrous tissue), as is usually seen in plantar lesions.
Palmar fibromatosis. In the early (proliferative) phase, palmar fascial or aponeurotic tissue is expanded by hypercellular spindle cell nodules.

Q: Sections of a painless nodule from the hand or foot revealing plump, bland fibroblasts with vesicular chromatin intimately associated with native fibrotendinous tissue is highly characteristic of [...].
Plantar fibromatosis. Intimate association of the cellular, proliferative-phase lesional spindle cells with native fibrotendinous tissue is seen.
Plantar fibromatosis. In the proliferative phase, plump, bland-appearing spindle cells with elongated nuclei with vesicular chromatin and inconspicuous nucleoli are predominant.
A: Palmar and Plantar Fibromatosis
Back Extra: Palmar and Plantar Fibromatosis
- Clinical: Palmar and Plantar Fibromatosis typically presents as painless nodules in the hands and feet, often leading to contractures and affecting adults, with a male predominance in palmar cases.
- Micro: Histologically, these lesions are characterized by proliferative phases with cellular spindle cell nodules and a collagenous stroma, with minimal atypia and rare mitotic figures.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Palmar and Plantar Fibromatosis.
Reference Gallery:
Plantar fibromatosis. Intimate association of the cellular, proliferative-phase lesional spindle cells with native fibrotendinous tissue is seen.
Plantar fibromatosis. Spindle cells arranged in long, parallel fascicles in more-densely collagenous matrix. The cells are uniform and lack discernible atypia. There are associated mild chronic inflammation and rare mitotic figures.
Plantar fibromatosis. In the proliferative phase, plump, bland-appearing spindle cells with elongated nuclei with vesicular chromatin and inconspicuous nucleoli are predominant.
Plantar fibromatosis. This lesion shows small numbers of osteoclast-type, multinucleated giant cells, interspersed among the plump, cellular fibroblastic cells.
Palmar fibromatosis. This early-stage lesion is cellular and shows loose fascicles of uniform spindle cells within prominent collagenous stroma.
Plantar fibromatosis. Low-power view showing typically multinodular growth pattern (within tendoaponeurotic fibrous tissue), as is usually seen in plantar lesions.
Palmar fibromatosis. In the early (proliferative) phase, palmar fascial or aponeurotic tissue is expanded by hypercellular spindle cell nodules.

Q: A mesenchymal neoplasm presenting with a "patternless" architecture, staghorn-shaped blood vessels, and a pathognomonic NAB2-STAT6 gene fusion is defined as a [...].
Solitary fibrous tumour. Tumours often have variable cellularity and a prominent ectatic, branching vasculature.
Solitary fibrous tumour. Hypocellular tumours often have a dense hyalinized collagenous stroma. Note the patternless architecture.
A: solitary fibrous tumor
Back Extra: Solitary Fibrous Tumour
- Clinical: Most solitary fibrous tumours present as slow-growing, painless masses. Abdominopelvic tumours may present with distention, constipation, urinary retention, or early satiety.
- Micro: Solitary fibrous tumours are composed of haphazardly arranged spindled to ovoid cells with indistinct, pale eosinophilic cytoplasm within a variably collagenous stroma, admixed with branching and hyalinized staghorn-shaped blood vessels.
- Ancillary: NAB2-STAT6 gene fusions are pathognomonic for solitary fibrous tumours. STAT6 immunohistochemistry is a sensitive and specific surrogate for all fusions.
Reference Gallery:
Solitary fibrous tumour. Grossly, the tumour is well circumscribed, with a tan, fleshy, multilobular cut surface.
Solitary fibrous tumour. Tumours often have variable cellularity and a prominent ectatic, branching vasculature.
Solitary fibrous tumour. Hypocellular tumours often have a dense hyalinized collagenous stroma. Note the patternless architecture.
Solitary fibrous tumour. Cellular tumours may have little intervening stromal collagen, and the vascular network may be obscured by tumour cells.
Solitary fibrous tumour. Tumour cells may be spindled or ovoid, as in this example.
Solitary fibrous tumour. Tumour cells typically display scant to moderate amounts of indistinct, palely eosinophilic cytoplasm and bland nuclei with fine pale chromatin and inconspicuous nucleoli.
Solitary fibrous tumour. Some tumours may have a predominantly collagenous appearance with few cellular areas.
Solitary fibrous tumour. Myxoid change is common and may predominate in tumours that have received neoadjuvant radiation.
Solitary fibrous tumour. Stromal and perivascular hyalinization is common.
Solitary fibrous tumour. Fat-forming (lipomatous) solitary fibrous tumour shows typical features of solitary fibrous tumour with areas of mature adipose tissue or scattered adipocytes.
Giant cell–rich solitary fibrous tumour. This lesion shows scattered multinucleated giant cells lining cystic spaces.
Dedifferentiated solitary fibrous tumour. This field shows an abrupt transition from typical solitary fibrous tumour (right) to an undifferentiated sarcoma (left; this example shows a pleomorphic myxoid sarcoma).

Q: Histologically, a solitary fibrous tumor displays a haphazard arrangement of spindled to ovoid cells admixed with a variably collagenous stroma and characteristic branching, [...]-shaped blood vessels.
Solitary fibrous tumour. Tumours often have variable cellularity and a prominent ectatic, branching vasculature.
Solitary fibrous tumour. Cellular tumours may have little intervening stromal collagen, and the vascular network may be obscured by tumour cells.
A: staghorn
Back Extra: Solitary Fibrous Tumour
- Clinical: Most solitary fibrous tumours present as slow-growing, painless masses. Abdominopelvic tumours may present with distention, constipation, urinary retention, or early satiety.
- Micro: Solitary fibrous tumours are composed of haphazardly arranged spindled to ovoid cells with indistinct, pale eosinophilic cytoplasm within a variably collagenous stroma, admixed with branching and hyalinized staghorn-shaped blood vessels.
- Ancillary: NAB2-STAT6 gene fusions are pathognomonic for solitary fibrous tumours. STAT6 immunohistochemistry is a sensitive and specific surrogate for all fusions.
Reference Gallery:
Solitary fibrous tumour. Grossly, the tumour is well circumscribed, with a tan, fleshy, multilobular cut surface.
Solitary fibrous tumour. Tumours often have variable cellularity and a prominent ectatic, branching vasculature.
Solitary fibrous tumour. Hypocellular tumours often have a dense hyalinized collagenous stroma. Note the patternless architecture.
Solitary fibrous tumour. Cellular tumours may have little intervening stromal collagen, and the vascular network may be obscured by tumour cells.
Solitary fibrous tumour. Tumour cells may be spindled or ovoid, as in this example.
Solitary fibrous tumour. Tumour cells typically display scant to moderate amounts of indistinct, palely eosinophilic cytoplasm and bland nuclei with fine pale chromatin and inconspicuous nucleoli.
Solitary fibrous tumour. Some tumours may have a predominantly collagenous appearance with few cellular areas.
Solitary fibrous tumour. Myxoid change is common and may predominate in tumours that have received neoadjuvant radiation.
Solitary fibrous tumour. Stromal and perivascular hyalinization is common.
Solitary fibrous tumour. Fat-forming (lipomatous) solitary fibrous tumour shows typical features of solitary fibrous tumour with areas of mature adipose tissue or scattered adipocytes.
Giant cell–rich solitary fibrous tumour. This lesion shows scattered multinucleated giant cells lining cystic spaces.
Dedifferentiated solitary fibrous tumour. This field shows an abrupt transition from typical solitary fibrous tumour (right) to an undifferentiated sarcoma (left; this example shows a pleomorphic myxoid sarcoma).

Q: The pathognomonic molecular driver for a solitary fibrous tumor is the [...] gene fusion, which results in strong nuclear positivity for its surrogate immunohistochemical marker.
Solitary fibrous tumour. Tumour cells may be spindled or ovoid, as in this example.
Solitary fibrous tumour. Tumour cells typically display scant to moderate amounts of indistinct, palely eosinophilic cytoplasm and bland nuclei with fine pale chromatin and inconspicuous nucleoli.
A: NAB2-STAT6
Back Extra: Solitary Fibrous Tumour
- Clinical: Most solitary fibrous tumours present as slow-growing, painless masses. Abdominopelvic tumours may present with distention, constipation, urinary retention, or early satiety.
- Micro: Solitary fibrous tumours are composed of haphazardly arranged spindled to ovoid cells with indistinct, pale eosinophilic cytoplasm within a variably collagenous stroma, admixed with branching and hyalinized staghorn-shaped blood vessels.
- Ancillary: NAB2-STAT6 gene fusions are pathognomonic for solitary fibrous tumours. STAT6 immunohistochemistry is a sensitive and specific surrogate for all fusions.
Reference Gallery:
Solitary fibrous tumour. Grossly, the tumour is well circumscribed, with a tan, fleshy, multilobular cut surface.
Solitary fibrous tumour. Tumours often have variable cellularity and a prominent ectatic, branching vasculature.
Solitary fibrous tumour. Hypocellular tumours often have a dense hyalinized collagenous stroma. Note the patternless architecture.
Solitary fibrous tumour. Cellular tumours may have little intervening stromal collagen, and the vascular network may be obscured by tumour cells.
Solitary fibrous tumour. Tumour cells may be spindled or ovoid, as in this example.
Solitary fibrous tumour. Tumour cells typically display scant to moderate amounts of indistinct, palely eosinophilic cytoplasm and bland nuclei with fine pale chromatin and inconspicuous nucleoli.
Solitary fibrous tumour. Some tumours may have a predominantly collagenous appearance with few cellular areas.
Solitary fibrous tumour. Myxoid change is common and may predominate in tumours that have received neoadjuvant radiation.
Solitary fibrous tumour. Stromal and perivascular hyalinization is common.
Solitary fibrous tumour. Fat-forming (lipomatous) solitary fibrous tumour shows typical features of solitary fibrous tumour with areas of mature adipose tissue or scattered adipocytes.
Giant cell–rich solitary fibrous tumour. This lesion shows scattered multinucleated giant cells lining cystic spaces.
Dedifferentiated solitary fibrous tumour. This field shows an abrupt transition from typical solitary fibrous tumour (right) to an undifferentiated sarcoma (left; this example shows a pleomorphic myxoid sarcoma).

Q: A superficial, circumscribed soft tissue mass displaying marked nuclear pleomorphism and frequent intranuclear pseudoinclusions, yet paradoxically demonstrating an extremely low mitotic count, is characteristic of [...].
CD34-positive fibroblastic tumour. The tumour presents as a circumscribed subcutaneous mass.
Superficial CD34-positive fibroblastic tumour. The cells show marked nuclear enlargement and pleomorphism, with frequent intranuclear pseudoinclusions; mitotic activity is extremely low.
A: Superficial CD34-positive fibroblastic tumor
Back Extra: Superficial CD34-positive fibroblastic tumour
- Clinical: Superficial CD34-positive fibroblastic tumour typically presents as a slow-growing, painless mass in the lower extremities, especially the thigh, with a median age of 37 years and a slight male predominance.
- Micro: The tumour is composed of highly cellular fascicles and sheets of spindled to epithelioid cells with abundant eosinophilic cytoplasm, marked nuclear pleomorphism, and a low mitotic count.
- Ancillary: Immunohistochemistry shows diffuse CD34 expression and patchy keratin expression, most often with the AE1/AE3 clones.
Reference Gallery:
CD34-positive fibroblastic tumour. The tumour presents as a circumscribed subcutaneous mass.
CD34-positive fibroblastic tumour. The tumour displays a fascicular to sheet-like proliferation of pleomorphic spindle cells with abundant, granular to glassy eosinophilic cytoplasm.
Superficial CD34-positive fibroblastic tumour. The tumour shows vague nuclear palisading, nuclear pleomorphism, and a mixed inflammatory infiltrate, including eosinophils.
Superficial CD34-positive fibroblastic tumour. The cells show marked nuclear enlargement and pleomorphism, with frequent intranuclear pseudoinclusions; mitotic activity is extremely low.
Superficial CD34-positive fibroblastic tumour. Diffuse CD34 expression is invariably present.
Superficial CD34-positive fibroblastic tumour. Patchy keratin expression, most often with the AE1/AE3 clones, is typically present.

Q: By immunohistochemistry, Superficial CD34-positive fibroblastic tumor is classically characterized by strong, diffuse expression of CD34 and patchy, aberrant expression of [...] (often utilizing AE1/AE3 clones).
Superficial CD34-positive fibroblastic tumour. Diffuse CD34 expression is invariably present.
Superficial CD34-positive fibroblastic tumour. Patchy keratin expression, most often with the AE1/AE3 clones, is typically present.
A: keratin
Back Extra: Superficial CD34-positive fibroblastic tumour
- Clinical: Superficial CD34-positive fibroblastic tumour typically presents as a slow-growing, painless mass in the lower extremities, especially the thigh, with a median age of 37 years and a slight male predominance.
- Micro: The tumour is composed of highly cellular fascicles and sheets of spindled to epithelioid cells with abundant eosinophilic cytoplasm, marked nuclear pleomorphism, and a low mitotic count.
- Ancillary: Immunohistochemistry shows diffuse CD34 expression and patchy keratin expression, most often with the AE1/AE3 clones.
Reference Gallery:
CD34-positive fibroblastic tumour. The tumour presents as a circumscribed subcutaneous mass.
CD34-positive fibroblastic tumour. The tumour displays a fascicular to sheet-like proliferation of pleomorphic spindle cells with abundant, granular to glassy eosinophilic cytoplasm.
Superficial CD34-positive fibroblastic tumour. The tumour shows vague nuclear palisading, nuclear pleomorphism, and a mixed inflammatory infiltrate, including eosinophils.
Superficial CD34-positive fibroblastic tumour. The cells show marked nuclear enlargement and pleomorphism, with frequent intranuclear pseudoinclusions; mitotic activity is extremely low.
Superficial CD34-positive fibroblastic tumour. Diffuse CD34 expression is invariably present.
Superficial CD34-positive fibroblastic tumour. Patchy keratin expression, most often with the AE1/AE3 clones, is typically present.

Q: Histologically, the neoplastic cells of Superficial CD34-positive fibroblastic tumor contain abundant, granular to glassy eosinophilic cytoplasm and are often accompanied by a mixed inflammatory infiltrate that characteristically includes [...].
CD34-positive fibroblastic tumour. The tumour displays a fascicular to sheet-like proliferation of pleomorphic spindle cells with abundant, granular to glassy eosinophilic cytoplasm.
Superficial CD34-positive fibroblastic tumour. The tumour shows vague nuclear palisading, nuclear pleomorphism, and a mixed inflammatory infiltrate, including eosinophils.
A: eosinophils
Back Extra: Superficial CD34-positive fibroblastic tumour
- Clinical: Superficial CD34-positive fibroblastic tumour typically presents as a slow-growing, painless mass in the lower extremities, especially the thigh, with a median age of 37 years and a slight male predominance.
- Micro: The tumour is composed of highly cellular fascicles and sheets of spindled to epithelioid cells with abundant eosinophilic cytoplasm, marked nuclear pleomorphism, and a low mitotic count.
- Ancillary: Immunohistochemistry shows diffuse CD34 expression and patchy keratin expression, most often with the AE1/AE3 clones.
Reference Gallery:
CD34-positive fibroblastic tumour. The tumour presents as a circumscribed subcutaneous mass.
CD34-positive fibroblastic tumour. The tumour displays a fascicular to sheet-like proliferation of pleomorphic spindle cells with abundant, granular to glassy eosinophilic cytoplasm.
Superficial CD34-positive fibroblastic tumour. The tumour shows vague nuclear palisading, nuclear pleomorphism, and a mixed inflammatory infiltrate, including eosinophils.
Superficial CD34-positive fibroblastic tumour. The cells show marked nuclear enlargement and pleomorphism, with frequent intranuclear pseudoinclusions; mitotic activity is extremely low.
Superficial CD34-positive fibroblastic tumour. Diffuse CD34 expression is invariably present.
Superficial CD34-positive fibroblastic tumour. Patchy keratin expression, most often with the AE1/AE3 clones, is typically present.

Q: In Adult Fibrosarcoma, the tumor is characteristically composed of relatively monomorphic spindle cells arranged in long, sweeping fascicles that form a distinct [...] pattern.
Adult fibrosarcoma. Low-power view shows a long fascicular growth with a focal classic herringbone pattern.
Adult fibrosarcoma. The tumour consists of monomorphic spindle cells with nuclear atypia.
A: herringbone
Back Extra: Adult Fibrosarcoma
- Clinical: Adult fibrosarcoma presents as a mass with or without pain, commonly involving the deep soft tissues of the extremities, trunk, and head and neck.
- Micro: The tumour is composed of relatively monomorphic spindle cells arranged in long, sweeping fascicles with a characteristic herringbone pattern.
- Ancillary: A recent report suggests a possible link to other NTRK-rearranged mesenchymal neoplasms due to an STRN3-NTRK3 fusion in adult fibrosarcoma.
Reference Gallery:
Adult fibrosarcoma. Low-power view shows a long fascicular growth with a focal classic herringbone pattern.
Adult fibrosarcoma. This high-grade tumour shows fascicular growth and necrosis.
Adult fibrosarcoma. The tumour consists of monomorphic spindle cells with nuclear atypia.
Adult fibrosarcoma. Radiation-induced adult fibrosarcoma showing monomorphic nuclear features.

Q: A high-grade deep soft tissue tumor exhibiting fascicular growth, focal necrosis, and monomorphic spindle cells (which can sometimes arise secondary to prior radiation exposure) is most characteristic of [...].
Adult fibrosarcoma. This high-grade tumour shows fascicular growth and necrosis.
Adult fibrosarcoma. Radiation-induced adult fibrosarcoma showing monomorphic nuclear features.
A: Adult Fibrosarcoma
Back Extra: Adult Fibrosarcoma
- Clinical: Adult fibrosarcoma presents as a mass with or without pain, commonly involving the deep soft tissues of the extremities, trunk, and head and neck.
- Micro: The tumour is composed of relatively monomorphic spindle cells arranged in long, sweeping fascicles with a characteristic herringbone pattern.
- Ancillary: A recent report suggests a possible link to other NTRK-rearranged mesenchymal neoplasms due to an STRN3-NTRK3 fusion in adult fibrosarcoma.
Reference Gallery:
Adult fibrosarcoma. Low-power view shows a long fascicular growth with a focal classic herringbone pattern.
Adult fibrosarcoma. This high-grade tumour shows fascicular growth and necrosis.
Adult fibrosarcoma. The tumour consists of monomorphic spindle cells with nuclear atypia.
Adult fibrosarcoma. Radiation-induced adult fibrosarcoma showing monomorphic nuclear features.

Q: Histologically, [...] is a bland spindle cell tumor characterized by a whorling or short fascicular pattern with an abrupt transition between hypocellular collagenous stroma and more cellular myxoid areas.
Low-grade fibromyxoid sarcoma. Low-grade fibromyxoid sarcoma is usually hypocellular and composed of areas with myxoid and fibrous stroma, often with an abrupt transition between the two areas.
Low-grade fibromyxoid sarcoma. Higher power showing the distinct fibrous and myxoid areas.
Low-grade fibromyxoid sarcoma. The tumour cells are spindled and cytologically bland and grow in short fascicles or in a storiform pattern.
A: Low-grade fibromyxoid sarcoma
Back Extra: Low-grade fibromyxoid sarcoma
- Clinical: Low-grade fibromyxoid sarcoma typically presents as a painless mass, often present for > 5 years.
- Micro: Characterized by alternating hypocellular collagenous and more-cellular myxoid areas with bland spindle cells in a whorling or short fascicular pattern.
- Ancillary: Diagnosis is confirmed by the presence of FUS-CREB3L2 or FUS-CREB3L1 gene fusions, and strong cytoplasmic MUC4 expression by immunohistochemistry.
Reference Gallery:
Low-grade fibromyxoid sarcoma. Low-grade fibromyxoid sarcoma is usually hypocellular and composed of areas with myxoid and fibrous stroma, often with an abrupt transition between the two areas.
Low-grade fibromyxoid sarcoma. Higher power showing the distinct fibrous and myxoid areas.
Low-grade fibromyxoid sarcoma. The tumour cells are spindled and cytologically bland and grow in short fascicles or in a storiform pattern.
Low-grade fibromyxoid sarcoma. Areas of hypercellularity.
Low-grade fibromyxoid sarcoma. Diffuse strong cytoplasmic expression of MUC4.
Low-grade fibromyxoid sarcoma. An example with giant collagen rosettes.
Low-grade fibromyxoid sarcoma. An example with giant collagen rosettes. The tumour cells surround nodules of hyaline collagen.

Q: Low-grade fibromyxoid sarcoma is frequently driven by FUS-CREB3L2 gene fusions and characteristically shows strong, diffuse cytoplasmic expression of [...] on immunohistochemistry.
Low-grade fibromyxoid sarcoma. Diffuse strong cytoplasmic expression of MUC4.
A: MUC4
Back Extra: Low-grade fibromyxoid sarcoma
- Clinical: Low-grade fibromyxoid sarcoma typically presents as a painless mass, often present for > 5 years.
- Micro: Characterized by alternating hypocellular collagenous and more-cellular myxoid areas with bland spindle cells in a whorling or short fascicular pattern.
- Ancillary: Diagnosis is confirmed by the presence of FUS-CREB3L2 or FUS-CREB3L1 gene fusions, and strong cytoplasmic MUC4 expression by immunohistochemistry.
Reference Gallery:
Low-grade fibromyxoid sarcoma. Low-grade fibromyxoid sarcoma is usually hypocellular and composed of areas with myxoid and fibrous stroma, often with an abrupt transition between the two areas.
Low-grade fibromyxoid sarcoma. Higher power showing the distinct fibrous and myxoid areas.
Low-grade fibromyxoid sarcoma. The tumour cells are spindled and cytologically bland and grow in short fascicles or in a storiform pattern.
Low-grade fibromyxoid sarcoma. Areas of hypercellularity.
Low-grade fibromyxoid sarcoma. Diffuse strong cytoplasmic expression of MUC4.
Low-grade fibromyxoid sarcoma. An example with giant collagen rosettes.
Low-grade fibromyxoid sarcoma. An example with giant collagen rosettes. The tumour cells surround nodules of hyaline collagen.

Q: A classic histologic variant of Low-grade fibromyxoid sarcoma features tumor cells arranged around nodules of hyaline collagen, forming characteristic structures known as [...].
Low-grade fibromyxoid sarcoma. An example with giant collagen rosettes.
Low-grade fibromyxoid sarcoma. An example with giant collagen rosettes. The tumour cells surround nodules of hyaline collagen.
A: giant collagen rosettes
Back Extra: Low-grade fibromyxoid sarcoma
- Clinical: Low-grade fibromyxoid sarcoma typically presents as a painless mass, often present for > 5 years.
- Micro: Characterized by alternating hypocellular collagenous and more-cellular myxoid areas with bland spindle cells in a whorling or short fascicular pattern.
- Ancillary: Diagnosis is confirmed by the presence of FUS-CREB3L2 or FUS-CREB3L1 gene fusions, and strong cytoplasmic MUC4 expression by immunohistochemistry.
Reference Gallery:
Low-grade fibromyxoid sarcoma. Low-grade fibromyxoid sarcoma is usually hypocellular and composed of areas with myxoid and fibrous stroma, often with an abrupt transition between the two areas.
Low-grade fibromyxoid sarcoma. Higher power showing the distinct fibrous and myxoid areas.
Low-grade fibromyxoid sarcoma. The tumour cells are spindled and cytologically bland and grow in short fascicles or in a storiform pattern.
Low-grade fibromyxoid sarcoma. Areas of hypercellularity.
Low-grade fibromyxoid sarcoma. Diffuse strong cytoplasmic expression of MUC4.
Low-grade fibromyxoid sarcoma. An example with giant collagen rosettes.
Low-grade fibromyxoid sarcoma. An example with giant collagen rosettes. The tumour cells surround nodules of hyaline collagen.

Q: A histologic hallmark of low-grade Myxofibrosarcoma is the presence of atypical fibroblastic cells set in a prominent myxoid stroma with elongated, [...] blood vessels.
Myxofibrosarcoma, low-grade. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown in Fig. #5859) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown here) and pseudolipoblasts (shown in Fig. #5861).
A: curvilinear
Back Extra: Myxofibrosarcoma
- Clinical: Myxofibrosarcoma predominantly affects elderly patients, with a slight male predominance, and presents as a slowly enlarging, painless mass in the limbs.
- Micro: Low-grade myxofibrosarcoma is hypocellular with atypical fibroblastic cells, hyperchromatic nuclei, and elongated, curvilinear blood vessels, while high-grade lesions are more cellular and pleomorphic.
- Ancillary: Karyotypes of myxofibrosarcomas show complex chromosomal abnormalities, with frequent gains of chromosome 5p and mutations in TP53, RB1, and CDKN2A/CDKN2B.
Reference Gallery:
Myxofibrosarcoma. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown here) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown in Fig. #5860) and pseudolipoblasts (shown in Fig. #5861).
Myxofibrosarcoma, low-grade. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown in Fig. #5859) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown here) and pseudolipoblasts (shown in Fig. #5861).
Myxofibrosarcoma, low-grade. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown in Fig. #5859) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown in Fig. #5860) and pseudolipoblasts (shown here).
Myxofibrosarcoma, intermediate-grade. Intermediate-grade myxofibrosarcomas retain myxoid stroma and the characteristic vascular pattern, but they are more cellular and pleomorphic than low-grade lesions.
Myxofibrosarcoma, high-grade. A component of the tumour with myxoid stroma and the typical vasculature is required to differentiate high-grade myxofibrosarcoma from undifferentiated pleomorphic sarcoma.
Myxofibrosarcoma, high-grade. A high-grade solid component resembling undifferentiated pleomorphic sarcoma is seen (bottom), juxtaposed to a myxoid area exhibiting typical features of myxofibrosarcoma (top).
Myxofibrosarcoma, high-grade. Frequent pleomorphic giant cells with eosinophilic cytoplasm are present in the high-grade component, mimicking high-grade undifferentiated pleomorphic sarcoma.
Epithelioid myxofibrosarcoma, high-grade. Note the large, somewhat discohesive epithelioid cells with copious eosinophilic cytoplasm.
Myxofibrosarcoma. Subcutaneous myxofibrosarcoma. Superficially located, high-grade myxofibrosarcoma with a multinodular growth pattern and a soft, gelatinous, myxoid cut surface.

Q: In addition to a myxoid matrix and characteristic vasculature, low-grade Myxofibrosarcoma frequently features vacuolated atypical cells known as [...].
Myxofibrosarcoma, low-grade. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown in Fig. #5859) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown in Fig. #5860) and pseudolipoblasts (shown here).
A: pseudolipoblasts
Back Extra: Myxofibrosarcoma
- Clinical: Myxofibrosarcoma predominantly affects elderly patients, with a slight male predominance, and presents as a slowly enlarging, painless mass in the limbs.
- Micro: Low-grade myxofibrosarcoma is hypocellular with atypical fibroblastic cells, hyperchromatic nuclei, and elongated, curvilinear blood vessels, while high-grade lesions are more cellular and pleomorphic.
- Ancillary: Karyotypes of myxofibrosarcomas show complex chromosomal abnormalities, with frequent gains of chromosome 5p and mutations in TP53, RB1, and CDKN2A/CDKN2B.
Reference Gallery:
Myxofibrosarcoma. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown here) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown in Fig. #5860) and pseudolipoblasts (shown in Fig. #5861).
Myxofibrosarcoma, low-grade. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown in Fig. #5859) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown here) and pseudolipoblasts (shown in Fig. #5861).
Myxofibrosarcoma, low-grade. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown in Fig. #5859) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown in Fig. #5860) and pseudolipoblasts (shown here).
Myxofibrosarcoma, intermediate-grade. Intermediate-grade myxofibrosarcomas retain myxoid stroma and the characteristic vascular pattern, but they are more cellular and pleomorphic than low-grade lesions.
Myxofibrosarcoma, high-grade. A component of the tumour with myxoid stroma and the typical vasculature is required to differentiate high-grade myxofibrosarcoma from undifferentiated pleomorphic sarcoma.
Myxofibrosarcoma, high-grade. A high-grade solid component resembling undifferentiated pleomorphic sarcoma is seen (bottom), juxtaposed to a myxoid area exhibiting typical features of myxofibrosarcoma (top).
Myxofibrosarcoma, high-grade. Frequent pleomorphic giant cells with eosinophilic cytoplasm are present in the high-grade component, mimicking high-grade undifferentiated pleomorphic sarcoma.
Epithelioid myxofibrosarcoma, high-grade. Note the large, somewhat discohesive epithelioid cells with copious eosinophilic cytoplasm.
Myxofibrosarcoma. Subcutaneous myxofibrosarcoma. Superficially located, high-grade myxofibrosarcoma with a multinodular growth pattern and a soft, gelatinous, myxoid cut surface.

Q: High-grade Myxofibrosarcoma can morphologically mimic undifferentiated pleomorphic sarcoma, but the diagnosis requires identifying areas with the tumor's characteristic [...] stroma, which grossly imparts a soft, gelatinous cut surface.
Myxofibrosarcoma, high-grade. A component of the tumour with myxoid stroma and the typical vasculature is required to differentiate high-grade myxofibrosarcoma from undifferentiated pleomorphic sarcoma.
Myxofibrosarcoma. Subcutaneous myxofibrosarcoma. Superficially located, high-grade myxofibrosarcoma with a multinodular growth pattern and a soft, gelatinous, myxoid cut surface.
A: myxoid
Back Extra: Myxofibrosarcoma
- Clinical: Myxofibrosarcoma predominantly affects elderly patients, with a slight male predominance, and presents as a slowly enlarging, painless mass in the limbs.
- Micro: Low-grade myxofibrosarcoma is hypocellular with atypical fibroblastic cells, hyperchromatic nuclei, and elongated, curvilinear blood vessels, while high-grade lesions are more cellular and pleomorphic.
- Ancillary: Karyotypes of myxofibrosarcomas show complex chromosomal abnormalities, with frequent gains of chromosome 5p and mutations in TP53, RB1, and CDKN2A/CDKN2B.
Reference Gallery:
Myxofibrosarcoma. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown here) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown in Fig. #5860) and pseudolipoblasts (shown in Fig. #5861).
Myxofibrosarcoma, low-grade. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown in Fig. #5859) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown here) and pseudolipoblasts (shown in Fig. #5861).
Myxofibrosarcoma, low-grade. A low-grade myxofibrosarcoma showing multinodular and highly infiltrative growth with a prominent myxoid matrix (shown in Fig. #5859) is characterized by the following features: a hypocellular appearance with atypical fibroblastic cells with hyperchromatic, pleomorphic nuclei and elongated, curvilinear blood vessels (shown in Fig. #5860) and pseudolipoblasts (shown here).
Myxofibrosarcoma, intermediate-grade. Intermediate-grade myxofibrosarcomas retain myxoid stroma and the characteristic vascular pattern, but they are more cellular and pleomorphic than low-grade lesions.
Myxofibrosarcoma, high-grade. A component of the tumour with myxoid stroma and the typical vasculature is required to differentiate high-grade myxofibrosarcoma from undifferentiated pleomorphic sarcoma.
Myxofibrosarcoma, high-grade. A high-grade solid component resembling undifferentiated pleomorphic sarcoma is seen (bottom), juxtaposed to a myxoid area exhibiting typical features of myxofibrosarcoma (top).
Myxofibrosarcoma, high-grade. Frequent pleomorphic giant cells with eosinophilic cytoplasm are present in the high-grade component, mimicking high-grade undifferentiated pleomorphic sarcoma.
Epithelioid myxofibrosarcoma, high-grade. Note the large, somewhat discohesive epithelioid cells with copious eosinophilic cytoplasm.
Myxofibrosarcoma. Subcutaneous myxofibrosarcoma. Superficially located, high-grade myxofibrosarcoma with a multinodular growth pattern and a soft, gelatinous, myxoid cut surface.

Q: Histologically, Sclerosing Epithelioid Fibrosarcoma is characterized by cords, nests, and trabeculae of epithelioid cells embedded in a dense [...] stroma, occasionally forming a pseudoalveolar pattern.
Sclerosing epithelioid fibrosarcoma. Low power shows small nests and cords of epithelioid cells in a dense sclerotic stroma.
Sclerosing epithelioid fibrosarcoma. Classic growth pattern of sclerosing epithelioid fibrosarcoma. This image shows cords and strands of epithelioid cells with pale cytoplasm and round to oval nuclei.
Sclerosing epithelioid fibrosarcoma. Classic growth pattern of sclerosing epithelioid fibrosarcoma. This image shows epithelioid cells arranged in trabeculae with a pseudoalveolar pattern.
A: hyalinized
Back Extra: Sclerosing Epithelioid Fibrosarcoma
- Clinical: Sclerosing epithelioid fibrosarcoma typically presents as a deep-seated mass in the extremities, trunk, or head and neck, with a higher incidence in middle-aged and elderly adults.
- Micro: The tumor is characterized by epithelioid cells arranged in cords, nests, or trabeculae, embedded in a dense hyalinized stroma, often with pseudoalveolar patterns.
- Ancillary: MUC4 is strongly and diffusely expressed in 80-90% of cases, and EWSR1-CREB3L1 rearrangements can confirm the diagnosis.
Reference Gallery:
Sclerosing epithelioid fibrosarcoma. Low power shows small nests and cords of epithelioid cells in a dense sclerotic stroma.
Sclerosing epithelioid fibrosarcoma. Classic growth pattern of sclerosing epithelioid fibrosarcoma. This image shows cords and strands of epithelioid cells with pale cytoplasm and round to oval nuclei.
Sclerosing epithelioid fibrosarcoma. Classic growth pattern of sclerosing epithelioid fibrosarcoma. This image shows epithelioid cells arranged in trabeculae with a pseudoalveolar pattern.
Sclerosing epithelioid fibrosarcoma. Sclerosing epithelioid fibrosarcoma with areas of solid growth and less-dense stroma.
Sclerosing epithelioid fibrosarcoma. Diffuse strong cytoplasmic expression of MUC4 in sclerosing epithelioid fibrosarcoma.
Sclerosing epithelioid fibrosarcoma. Deep, large sclerosing epithelioid fibrosarcoma of the upper arm.
Sclerosing epithelioid fibrosarcoma. Sclerosing epithelioid fibrosarcoma showing abrupt transition to areas of low-grade fibromyxoid sarcoma.

Q: Immunohistochemistry for Sclerosing Epithelioid Fibrosarcoma typically demonstrates strong, diffuse cytoplasmic expression of [...], which helps confirm the diagnosis alongside an EWSR1-CREB3L1 rearrangement.
Sclerosing epithelioid fibrosarcoma. Diffuse strong cytoplasmic expression of MUC4 in sclerosing epithelioid fibrosarcoma.
A: MUC4
Back Extra: Sclerosing Epithelioid Fibrosarcoma
- Clinical: Sclerosing epithelioid fibrosarcoma typically presents as a deep-seated mass in the extremities, trunk, or head and neck, with a higher incidence in middle-aged and elderly adults.
- Micro: The tumor is characterized by epithelioid cells arranged in cords, nests, or trabeculae, embedded in a dense hyalinized stroma, often with pseudoalveolar patterns.
- Ancillary: MUC4 is strongly and diffusely expressed in 80-90% of cases, and EWSR1-CREB3L1 rearrangements can confirm the diagnosis.
Reference Gallery:
Sclerosing epithelioid fibrosarcoma. Low power shows small nests and cords of epithelioid cells in a dense sclerotic stroma.
Sclerosing epithelioid fibrosarcoma. Classic growth pattern of sclerosing epithelioid fibrosarcoma. This image shows cords and strands of epithelioid cells with pale cytoplasm and round to oval nuclei.
Sclerosing epithelioid fibrosarcoma. Classic growth pattern of sclerosing epithelioid fibrosarcoma. This image shows epithelioid cells arranged in trabeculae with a pseudoalveolar pattern.
Sclerosing epithelioid fibrosarcoma. Sclerosing epithelioid fibrosarcoma with areas of solid growth and less-dense stroma.
Sclerosing epithelioid fibrosarcoma. Diffuse strong cytoplasmic expression of MUC4 in sclerosing epithelioid fibrosarcoma.
Sclerosing epithelioid fibrosarcoma. Deep, large sclerosing epithelioid fibrosarcoma of the upper arm.
Sclerosing epithelioid fibrosarcoma. Sclerosing epithelioid fibrosarcoma showing abrupt transition to areas of low-grade fibromyxoid sarcoma.

Q: Sclerosing Epithelioid Fibrosarcoma is closely related genetically and morphologically to [...], and tumors can occasionally show an abrupt transition between these two distinct morphologies.
Sclerosing epithelioid fibrosarcoma. Sclerosing epithelioid fibrosarcoma showing abrupt transition to areas of low-grade fibromyxoid sarcoma.
A: low-grade fibromyxoid sarcoma
Back Extra: Sclerosing Epithelioid Fibrosarcoma
- Clinical: Sclerosing epithelioid fibrosarcoma typically presents as a deep-seated mass in the extremities, trunk, or head and neck, with a higher incidence in middle-aged and elderly adults.
- Micro: The tumor is characterized by epithelioid cells arranged in cords, nests, or trabeculae, embedded in a dense hyalinized stroma, often with pseudoalveolar patterns.
- Ancillary: MUC4 is strongly and diffusely expressed in 80-90% of cases, and EWSR1-CREB3L1 rearrangements can confirm the diagnosis.
Reference Gallery:
Sclerosing epithelioid fibrosarcoma. Low power shows small nests and cords of epithelioid cells in a dense sclerotic stroma.
Sclerosing epithelioid fibrosarcoma. Classic growth pattern of sclerosing epithelioid fibrosarcoma. This image shows cords and strands of epithelioid cells with pale cytoplasm and round to oval nuclei.
Sclerosing epithelioid fibrosarcoma. Classic growth pattern of sclerosing epithelioid fibrosarcoma. This image shows epithelioid cells arranged in trabeculae with a pseudoalveolar pattern.
Sclerosing epithelioid fibrosarcoma. Sclerosing epithelioid fibrosarcoma with areas of solid growth and less-dense stroma.
Sclerosing epithelioid fibrosarcoma. Diffuse strong cytoplasmic expression of MUC4 in sclerosing epithelioid fibrosarcoma.
Sclerosing epithelioid fibrosarcoma. Deep, large sclerosing epithelioid fibrosarcoma of the upper arm.
Sclerosing epithelioid fibrosarcoma. Sclerosing epithelioid fibrosarcoma showing abrupt transition to areas of low-grade fibromyxoid sarcoma.

Q: Histologically, Deep Fibrous Histiocytoma displays a monomorphic population of spindled cells arranged in a classic [...] architecture.
Deep fibrous histiocytoma. Tumour cells are generally uniform, with less cytological pleomorphism than their dermal counterparts.
Deep fibrous histiocytoma. Monomorphic storiform pattern is typical.
A: storiform
Back Extra: Deep Fibrous Histiocytoma
- Clinical: Most lesions present as a painless, slowly enlarging mass, commonly affecting the extremities.
- Micro: Well-circumscribed lesions with a storiform architecture, spindled cells, and haemangiopericytoma-like vessels.
- Ancillary: PRKCB/PRKCD rearrangements are common, and CD34 positivity is frequent.
Reference Gallery:
Deep fibrous histiocytoma. Tumour cells are generally uniform, with less cytological pleomorphism than their dermal counterparts.
Deep fibrous histiocytoma. Monomorphic storiform pattern is typical.
Deep fibrous histiocytoma. Thin-walled branching (haemangiopericytoma-like) vessels are common.
Deep fibrous histiocytoma. Tumours often arise in the subcutis and are well circumscribed, often with a fibrous pseudocapsule.

Q: A prominent histologic feature of Deep Fibrous Histiocytoma is the presence of thin-walled, branching vessels that are commonly described as [...].
Deep fibrous histiocytoma. Thin-walled branching (haemangiopericytoma-like) vessels are common.
A: hemangiopericytoma-like
Back Extra: Deep Fibrous Histiocytoma
- Clinical: Most lesions present as a painless, slowly enlarging mass, commonly affecting the extremities.
- Micro: Well-circumscribed lesions with a storiform architecture, spindled cells, and haemangiopericytoma-like vessels.
- Ancillary: PRKCB/PRKCD rearrangements are common, and CD34 positivity is frequent.
Reference Gallery:
Deep fibrous histiocytoma. Tumour cells are generally uniform, with less cytological pleomorphism than their dermal counterparts.
Deep fibrous histiocytoma. Monomorphic storiform pattern is typical.
Deep fibrous histiocytoma. Thin-walled branching (haemangiopericytoma-like) vessels are common.
Deep fibrous histiocytoma. Tumours often arise in the subcutis and are well circumscribed, often with a fibrous pseudocapsule.

Q: Unlike its dermal counterpart, Deep Fibrous Histiocytoma typically arises in the subcutis as a well-circumscribed mass, frequently surrounded by a fibrous [...].
Deep fibrous histiocytoma. Tumours often arise in the subcutis and are well circumscribed, often with a fibrous pseudocapsule.
A: pseudocapsule
Back Extra: Deep Fibrous Histiocytoma
- Clinical: Most lesions present as a painless, slowly enlarging mass, commonly affecting the extremities.
- Micro: Well-circumscribed lesions with a storiform architecture, spindled cells, and haemangiopericytoma-like vessels.
- Ancillary: PRKCB/PRKCD rearrangements are common, and CD34 positivity is frequent.
Reference Gallery:
Deep fibrous histiocytoma. Tumour cells are generally uniform, with less cytological pleomorphism than their dermal counterparts.
Deep fibrous histiocytoma. Monomorphic storiform pattern is typical.
Deep fibrous histiocytoma. Thin-walled branching (haemangiopericytoma-like) vessels are common.
Deep fibrous histiocytoma. Tumours often arise in the subcutis and are well circumscribed, often with a fibrous pseudocapsule.

Q: Microscopically, Plexiform Fibrohistiocytic Tumor shows a characteristic plexiform growth pattern in the dermis and subcutaneous tissue, featuring small nodules of histiocytoid cells admixed with [...] and surrounded by spindle cells.
Plexiform fibrohistiocytic tumour. The distinctive nodules are distributed within adipose tissue in a plexiform distribution.
Plexiform fibrohistiocytic tumour. The nodules are composed of bland and uniform epithelioid cells with admixed osteoclast-like multinucleated giant cells.
A: osteoclast-like multinucleated giant cells
Back Extra: Plexiform Fibrohistiocytic Tumour
- Clinical: Plexiform fibrohistiocytic tumour commonly presents as slow-growing, ill-defined plaques and nodules in the upper limbs, with a median age of 14.5–20 years and an equal sex distribution.
- Micro: The tumour shows a plexiform growth pattern in the dermis and subcutaneous adipose tissue, with small nodules of histiocytoid cells and osteoclast-like multinucleated giant cells surrounded by spindle cells.
- Ancillary: Immunohistochemistry typically shows spindle cells expressing SMA.
Reference Gallery:
Plexiform fibrohistiocytic tumour. The tumour shows a plexiform growth in deep dermis and subcutaneous adipose tissue.
Plexiform fibrohistiocytic tumour. Note the infiltrative tumour growth within subcutaneous adipose tissue and extension into skeletal muscle.
Plexiform fibrohistiocytic tumour. Bland-appearing spindle cells are arranged in intersecting fascicles.
Plexiform fibrohistiocytic tumour. The distinctive nodules are distributed within adipose tissue in a plexiform distribution.
Plexiform fibrohistiocytic tumour. The nodules are composed of bland and uniform epithelioid cells with admixed osteoclast-like multinucleated giant cells.

Q: An adolescent presents with an ill-defined plaque on the upper limb. Histology reveals an infiltrative, plexiform growth pattern in the deep dermis and subcutaneous fat, consisting of intersecting fascicles of bland spindle cells and distinct nodules of histiocytoid cells. This morphology is classic for a [...].
Plexiform fibrohistiocytic tumour. The tumour shows a plexiform growth in deep dermis and subcutaneous adipose tissue.
Plexiform fibrohistiocytic tumour. Note the infiltrative tumour growth within subcutaneous adipose tissue and extension into skeletal muscle.
Plexiform fibrohistiocytic tumour. Bland-appearing spindle cells are arranged in intersecting fascicles.
A: Plexiform Fibrohistiocytic Tumor
Back Extra: Plexiform Fibrohistiocytic Tumour
- Clinical: Plexiform fibrohistiocytic tumour commonly presents as slow-growing, ill-defined plaques and nodules in the upper limbs, with a median age of 14.5–20 years and an equal sex distribution.
- Micro: The tumour shows a plexiform growth pattern in the dermis and subcutaneous adipose tissue, with small nodules of histiocytoid cells and osteoclast-like multinucleated giant cells surrounded by spindle cells.
- Ancillary: Immunohistochemistry typically shows spindle cells expressing SMA.
Reference Gallery:
Plexiform fibrohistiocytic tumour. The tumour shows a plexiform growth in deep dermis and subcutaneous adipose tissue.
Plexiform fibrohistiocytic tumour. Note the infiltrative tumour growth within subcutaneous adipose tissue and extension into skeletal muscle.
Plexiform fibrohistiocytic tumour. Bland-appearing spindle cells are arranged in intersecting fascicles.
Plexiform fibrohistiocytic tumour. The distinctive nodules are distributed within adipose tissue in a plexiform distribution.
Plexiform fibrohistiocytic tumour. The nodules are composed of bland and uniform epithelioid cells with admixed osteoclast-like multinucleated giant cells.

Q: Histologically, a tenosynovial giant cell tumor classically demonstrates an admixture of small histiocyte-like cells, larger epithelioid cells, and characteristic multinucleated [...].
Tenosynovial giant cell tumour, localized type. Tumours are composed of an admixture of small histiocyte-like cells, larger epithelioid cells, and osteoclast-like giant cells.
A: osteoclast-like giant cells
Q: Tenosynovial Giant Cell Tumour
- Clinical: Localized-type [...] presents as a painless mass, while the diffuse type is associated with pain, tenderness, swelling, or limitation of motion.
- Micro: The microscopic appearance of [...] varies, often showing an admixture of small histiocyte-like cells, larger epithelioid cells, and osteoclast-like giant cells.
- Ancillary: Essential for diagnosis: intra- or extra-articular location, varying proportions of small histiocytic cells, large amphophilic cells, foam cells, and multinucleated giant cells. Demonstration of CSF1 rearrangement is desirable in some cases.
Reference Gallery:
Malignant tenosynovial giant cell tumour. Sheets of large mononuclear cells, with enlarged nuclei and increased mitotic activity.
Tenosynovial giant cell tumour, localized type. Some cases of both localized and diffuse types contain numerous desmin-positive mononuclear cells, often with dendritic processes.
Tenosynovial giant cell tumour, diffuse type. Villous appearance of an intra-articular tumour.
Tenosynovial giant cell tumour, diffuse type. Purely extra-articular tumour infiltrating muscular and adipose tissue.
Tenosynovial giant cell tumour, localized type. Tumours are composed of an admixture of small histiocyte-like cells, larger epithelioid cells, and osteoclast-like giant cells.
Tenosynovial giant cell tumour, localized type. The cytoplasm of larger mononuclear cells often contains a peripheral rim of haemosiderin.
Tenosynovial giant cell tumour, localized type. The stroma shows variable degrees of hyalinization.
Tenosynovial giant cell tumour, localized type. Collections of foamy histiocytes are common.
Tenosynovial giant cell tumour, diffuse type. Pseudosynovial clefts are common.
Tenosynovial giant cell tumour, diffuse type. Osteoclast-like giant cells may be absent or extremely rare in the diffuse type.
A: Tenosynovial Giant Cell Tumour; Tenosynovial Giant Cell Tumour

Q: Microscopically, the larger mononuclear cells in a tenosynovial giant cell tumor frequently display a characteristic peripheral rim of [...] pigment in their cytoplasm.
Tenosynovial giant cell tumour, localized type. The cytoplasm of larger mononuclear cells often contains a peripheral rim of haemosiderin.
A: hemosiderin
Q: Tenosynovial Giant Cell Tumour
- Clinical: Localized-type [...] presents as a painless mass, while the diffuse type is associated with pain, tenderness, swelling, or limitation of motion.
- Micro: The microscopic appearance of [...] varies, often showing an admixture of small histiocyte-like cells, larger epithelioid cells, and osteoclast-like giant cells.
- Ancillary: Essential for diagnosis: intra- or extra-articular location, varying proportions of small histiocytic cells, large amphophilic cells, foam cells, and multinucleated giant cells. Demonstration of CSF1 rearrangement is desirable in some cases.
Reference Gallery:
Malignant tenosynovial giant cell tumour. Sheets of large mononuclear cells, with enlarged nuclei and increased mitotic activity.
Tenosynovial giant cell tumour, localized type. Some cases of both localized and diffuse types contain numerous desmin-positive mononuclear cells, often with dendritic processes.
Tenosynovial giant cell tumour, diffuse type. Villous appearance of an intra-articular tumour.
Tenosynovial giant cell tumour, diffuse type. Purely extra-articular tumour infiltrating muscular and adipose tissue.
Tenosynovial giant cell tumour, localized type. Tumours are composed of an admixture of small histiocyte-like cells, larger epithelioid cells, and osteoclast-like giant cells.
Tenosynovial giant cell tumour, localized type. The cytoplasm of larger mononuclear cells often contains a peripheral rim of haemosiderin.
Tenosynovial giant cell tumour, localized type. The stroma shows variable degrees of hyalinization.
Tenosynovial giant cell tumour, localized type. Collections of foamy histiocytes are common.
Tenosynovial giant cell tumour, diffuse type. Pseudosynovial clefts are common.
Tenosynovial giant cell tumour, diffuse type. Osteoclast-like giant cells may be absent or extremely rare in the diffuse type.
A: Tenosynovial Giant Cell Tumour; Tenosynovial Giant Cell Tumour

Q: Macroscopically, the intra-articular diffuse type of tenosynovial giant cell tumor often exhibits a characteristic [...] architecture.
Tenosynovial giant cell tumour, diffuse type. Villous appearance of an intra-articular tumour.
A: villous
Q: Tenosynovial Giant Cell Tumour
- Clinical: Localized-type [...] presents as a painless mass, while the diffuse type is associated with pain, tenderness, swelling, or limitation of motion.
- Micro: The microscopic appearance of [...] varies, often showing an admixture of small histiocyte-like cells, larger epithelioid cells, and osteoclast-like giant cells.
- Ancillary: Essential for diagnosis: intra- or extra-articular location, varying proportions of small histiocytic cells, large amphophilic cells, foam cells, and multinucleated giant cells. Demonstration of CSF1 rearrangement is desirable in some cases.
Reference Gallery:
Malignant tenosynovial giant cell tumour. Sheets of large mononuclear cells, with enlarged nuclei and increased mitotic activity.
Tenosynovial giant cell tumour, localized type. Some cases of both localized and diffuse types contain numerous desmin-positive mononuclear cells, often with dendritic processes.
Tenosynovial giant cell tumour, diffuse type. Villous appearance of an intra-articular tumour.
Tenosynovial giant cell tumour, diffuse type. Purely extra-articular tumour infiltrating muscular and adipose tissue.
Tenosynovial giant cell tumour, localized type. Tumours are composed of an admixture of small histiocyte-like cells, larger epithelioid cells, and osteoclast-like giant cells.
Tenosynovial giant cell tumour, localized type. The cytoplasm of larger mononuclear cells often contains a peripheral rim of haemosiderin.
Tenosynovial giant cell tumour, localized type. The stroma shows variable degrees of hyalinization.
Tenosynovial giant cell tumour, localized type. Collections of foamy histiocytes are common.
Tenosynovial giant cell tumour, diffuse type. Pseudosynovial clefts are common.
Tenosynovial giant cell tumour, diffuse type. Osteoclast-like giant cells may be absent or extremely rare in the diffuse type.
A: Tenosynovial Giant Cell Tumour; Tenosynovial Giant Cell Tumour

Q: A superficial soft tissue tumor displaying blood-filled pseudoangiomatous spaces, a fibrous pseudocapsule, and a peripheral lymphoplasmacytic cuff mimicking a lymph node is highly characteristic of [...].
Angiomatoid fibrous histiocytoma. A well-circumscribed tumour displaying multinodular fibrohistiocytic proliferation, pseudocystic spaces filled with blood, and a peripheral rim of lymphoid tissue, simulating a metastatic lymph node.
Angiomatoid fibrous histiocytoma. Tumour nodule surrounded by a characteristic lymphoplasmacytic cuff.
A: Angiomatoid Fibrous Histiocytoma
Back Extra: Angiomatoid Fibrous Histiocytoma
- Clinical: Angiomatoid fibrous histiocytoma typically presents as a slow-growing, superficial, painless soft tissue mass, often in the extremities.
- Micro: Characterized by solid nodules of epithelioid to spindle cells, pseudoangiomatous spaces, a fibrous pseudocapsule, and a lymphoplasmacytic cuff.
- Ancillary: Most cases have the t(2;22)(q33;q12) translocation, resulting in an EWSR1-CREB1 fusion.
Reference Gallery:
Angiomatoid fibrous histiocytoma. A well-circumscribed tumour displaying multinodular fibrohistiocytic proliferation, pseudocystic spaces filled with blood, and a peripheral rim of lymphoid tissue, simulating a metastatic lymph node.
Angiomatoid fibrous histiocytoma. More-pleomorphic tumour cells containing a moderate amount of cytoplasm, vesicular nuclei, and focal intranuclear pseudoinclusions along with interspersed lymphocytes and plasma cells.
Angiomatoid fibrous histiocytoma. Mitoses are generally infrequent.
Angiomatoid fibrous histiocytoma. Substantial desmin immunoreactivity in a case of angiomatoid fibrous histiocytoma.
Angiomatoid fibrous histiocytoma. EWSR1 gene rearrangement detected, in the form of single red-green split signals, identified in the various tumour cells.
Angiomatoid fibrous histiocytoma. Tumour nodule surrounded by a characteristic lymphoplasmacytic cuff.
Angiomatoid fibrous histiocytoma. In this case from the retroperitoneum, tumour cells within a prominent myxoid stroma are surrounded by a lymphoplasmacytic cuff.

Q: FISH analysis of Angiomatoid Fibrous Histiocytoma characteristically demonstrates a rearrangement of the [...] gene, most commonly resulting in a t(2;22) translocation with CREB1.
Angiomatoid fibrous histiocytoma. EWSR1 gene rearrangement detected, in the form of single red-green split signals, identified in the various tumour cells.
A: EWSR1
Back Extra: Angiomatoid Fibrous Histiocytoma
- Clinical: Angiomatoid fibrous histiocytoma typically presents as a slow-growing, superficial, painless soft tissue mass, often in the extremities.
- Micro: Characterized by solid nodules of epithelioid to spindle cells, pseudoangiomatous spaces, a fibrous pseudocapsule, and a lymphoplasmacytic cuff.
- Ancillary: Most cases have the t(2;22)(q33;q12) translocation, resulting in an EWSR1-CREB1 fusion.
Reference Gallery:
Angiomatoid fibrous histiocytoma. A well-circumscribed tumour displaying multinodular fibrohistiocytic proliferation, pseudocystic spaces filled with blood, and a peripheral rim of lymphoid tissue, simulating a metastatic lymph node.
Angiomatoid fibrous histiocytoma. More-pleomorphic tumour cells containing a moderate amount of cytoplasm, vesicular nuclei, and focal intranuclear pseudoinclusions along with interspersed lymphocytes and plasma cells.
Angiomatoid fibrous histiocytoma. Mitoses are generally infrequent.
Angiomatoid fibrous histiocytoma. Substantial desmin immunoreactivity in a case of angiomatoid fibrous histiocytoma.
Angiomatoid fibrous histiocytoma. EWSR1 gene rearrangement detected, in the form of single red-green split signals, identified in the various tumour cells.
Angiomatoid fibrous histiocytoma. Tumour nodule surrounded by a characteristic lymphoplasmacytic cuff.
Angiomatoid fibrous histiocytoma. In this case from the retroperitoneum, tumour cells within a prominent myxoid stroma are surrounded by a lymphoplasmacytic cuff.

Q: Although primarily a fibrohistiocytic proliferation, Angiomatoid Fibrous Histiocytoma frequently demonstrates substantial immunohistochemical positivity for [...].
Angiomatoid fibrous histiocytoma. Substantial desmin immunoreactivity in a case of angiomatoid fibrous histiocytoma.
A: desmin
Back Extra: Angiomatoid Fibrous Histiocytoma
- Clinical: Angiomatoid fibrous histiocytoma typically presents as a slow-growing, superficial, painless soft tissue mass, often in the extremities.
- Micro: Characterized by solid nodules of epithelioid to spindle cells, pseudoangiomatous spaces, a fibrous pseudocapsule, and a lymphoplasmacytic cuff.
- Ancillary: Most cases have the t(2;22)(q33;q12) translocation, resulting in an EWSR1-CREB1 fusion.
Reference Gallery:
Angiomatoid fibrous histiocytoma. A well-circumscribed tumour displaying multinodular fibrohistiocytic proliferation, pseudocystic spaces filled with blood, and a peripheral rim of lymphoid tissue, simulating a metastatic lymph node.
Angiomatoid fibrous histiocytoma. More-pleomorphic tumour cells containing a moderate amount of cytoplasm, vesicular nuclei, and focal intranuclear pseudoinclusions along with interspersed lymphocytes and plasma cells.
Angiomatoid fibrous histiocytoma. Mitoses are generally infrequent.
Angiomatoid fibrous histiocytoma. Substantial desmin immunoreactivity in a case of angiomatoid fibrous histiocytoma.
Angiomatoid fibrous histiocytoma. EWSR1 gene rearrangement detected, in the form of single red-green split signals, identified in the various tumour cells.
Angiomatoid fibrous histiocytoma. Tumour nodule surrounded by a characteristic lymphoplasmacytic cuff.
Angiomatoid fibrous histiocytoma. In this case from the retroperitoneum, tumour cells within a prominent myxoid stroma are surrounded by a lymphoplasmacytic cuff.

Q: A rapidly growing, exophytic, and often ulcerated dermal nodule on the sun-damaged skin of an elderly patient, characterized by a well-circumscribed proliferation of highly pleomorphic cells with numerous mitoses, represents [...].
Atypical fibroxanthoma. Clinically, atypical fibroxanthoma presents as a small, exophytic, often ulcerated dermal neoplasm.
Atypical fibroxanthoma. Low-power view shows a nodular, well-circumscribed, dermal neoplasm with collarette formation of the hyperplastic epidermis.
Atypical fibroxanthoma. Cellular neoplasm composed of atypical spindled, round, polygonal, and pleomorphic tumour cells; numerous mitoses are present.
A: Atypical fibroxanthoma
Back Extra: Atypical fibroxanthoma
- Clinical: Atypical fibroxanthoma (AFX) is a rare mesenchymal neoplasm that typically presents as a solitary, fast-growing, exophytic, dome-shaped nodule, often < 2 cm and ulcerated, mostly in sun-damaged skin of elderly white patients.
- Micro: AFX is characterized by a cellular neoplasm composed of highly pleomorphic polygonal or histiocytoid cells, enlarged and atypical spindled and epithelioid cells, with numerous mitoses and atypical nuclear features.
- Ancillary: Immunohistochemically, AFX is positive for vimentin, CD10, and p53, and often SMA. It is consistently negative for keratins, S100, and SOX10, with a characteristic TP53 mutation pattern.
Reference Gallery:
Atypical fibroxanthoma. Clinically, atypical fibroxanthoma presents as a small, exophytic, often ulcerated dermal neoplasm.
Atypical fibroxanthoma. Low-power view shows a nodular, well-circumscribed, dermal neoplasm with collarette formation of the hyperplastic epidermis.
Atypical fibroxanthoma. Cellular neoplasm composed of atypical spindled, round, polygonal, and pleomorphic tumour cells; numerous mitoses are present.
Spindle cell atypical fibroxanthoma. Cellular bundles and fascicles composed of atypical spindled cells with numerous mitoses are noted.
Osteoclast-like giant cell–rich atypical fibroxanthoma. Numerous osteoclast-like giant cells with small, bland nuclei are admixed.
Keloidal atypical fibroxanthoma. Thick bundles of hyalinized collagen masking nuclear atypia.
Granular cell atypical fibroxanthoma. Tumour cells contain abundant granular cytoplasm and enlarged nuclei.

Q: The keloidal variant of Atypical fibroxanthoma is a histopathologic subtype uniquely characterized by thick bundles of [...] that can obscure the underlying nuclear atypia of the tumor cells.
Keloidal atypical fibroxanthoma. Thick bundles of hyalinized collagen masking nuclear atypia.
A: hyalinized collagen
Back Extra: Atypical fibroxanthoma
- Clinical: Atypical fibroxanthoma (AFX) is a rare mesenchymal neoplasm that typically presents as a solitary, fast-growing, exophytic, dome-shaped nodule, often < 2 cm and ulcerated, mostly in sun-damaged skin of elderly white patients.
- Micro: AFX is characterized by a cellular neoplasm composed of highly pleomorphic polygonal or histiocytoid cells, enlarged and atypical spindled and epithelioid cells, with numerous mitoses and atypical nuclear features.
- Ancillary: Immunohistochemically, AFX is positive for vimentin, CD10, and p53, and often SMA. It is consistently negative for keratins, S100, and SOX10, with a characteristic TP53 mutation pattern.
Reference Gallery:
Atypical fibroxanthoma. Clinically, atypical fibroxanthoma presents as a small, exophytic, often ulcerated dermal neoplasm.
Atypical fibroxanthoma. Low-power view shows a nodular, well-circumscribed, dermal neoplasm with collarette formation of the hyperplastic epidermis.
Atypical fibroxanthoma. Cellular neoplasm composed of atypical spindled, round, polygonal, and pleomorphic tumour cells; numerous mitoses are present.
Spindle cell atypical fibroxanthoma. Cellular bundles and fascicles composed of atypical spindled cells with numerous mitoses are noted.
Osteoclast-like giant cell–rich atypical fibroxanthoma. Numerous osteoclast-like giant cells with small, bland nuclei are admixed.
Keloidal atypical fibroxanthoma. Thick bundles of hyalinized collagen masking nuclear atypia.
Granular cell atypical fibroxanthoma. Tumour cells contain abundant granular cytoplasm and enlarged nuclei.

Q: The osteoclast-like giant cell-rich variant of Atypical fibroxanthoma features an admixture of highly atypical mononuclear tumor cells and numerous [...] that paradoxically possess small, bland nuclei.
Osteoclast-like giant cell–rich atypical fibroxanthoma. Numerous osteoclast-like giant cells with small, bland nuclei are admixed.
A: osteoclast-like giant cells
Back Extra: Atypical fibroxanthoma
- Clinical: Atypical fibroxanthoma (AFX) is a rare mesenchymal neoplasm that typically presents as a solitary, fast-growing, exophytic, dome-shaped nodule, often < 2 cm and ulcerated, mostly in sun-damaged skin of elderly white patients.
- Micro: AFX is characterized by a cellular neoplasm composed of highly pleomorphic polygonal or histiocytoid cells, enlarged and atypical spindled and epithelioid cells, with numerous mitoses and atypical nuclear features.
- Ancillary: Immunohistochemically, AFX is positive for vimentin, CD10, and p53, and often SMA. It is consistently negative for keratins, S100, and SOX10, with a characteristic TP53 mutation pattern.
Reference Gallery:
Atypical fibroxanthoma. Clinically, atypical fibroxanthoma presents as a small, exophytic, often ulcerated dermal neoplasm.
Atypical fibroxanthoma. Low-power view shows a nodular, well-circumscribed, dermal neoplasm with collarette formation of the hyperplastic epidermis.
Atypical fibroxanthoma. Cellular neoplasm composed of atypical spindled, round, polygonal, and pleomorphic tumour cells; numerous mitoses are present.
Spindle cell atypical fibroxanthoma. Cellular bundles and fascicles composed of atypical spindled cells with numerous mitoses are noted.
Osteoclast-like giant cell–rich atypical fibroxanthoma. Numerous osteoclast-like giant cells with small, bland nuclei are admixed.
Keloidal atypical fibroxanthoma. Thick bundles of hyalinized collagen masking nuclear atypia.
Granular cell atypical fibroxanthoma. Tumour cells contain abundant granular cytoplasm and enlarged nuclei.

Q: Histologically, Giant Cell Tumor of Soft Tissue features a characteristic multinodular architecture with fibrous septa separating a mixture of ovoid mononuclear cells and multinucleated [...] giant cells.
Giant cell tumour of soft tissue. Giant cell tumour of soft tissue shows a characteristic multinodular architecture where clusters of osteoclast-like multinucleated giant cells are often separated by fibrous septa. Metaplastic bone formation is also commonly observed (bottom).
Giant cell tumour of soft tissue. The cellular nodules contain a mixture of round/oval mononuclear and multinucleated osteoclast-like giant cells.
A: osteoclast-like
Back Extra: Giant Cell Tumour of Soft Tissue
- Clinical: Giant cell tumour of soft tissue usually presents as a painless growing mass with an average duration of 6 months, and is most common in the fifth decade of life.
- Micro: The tumour displays a multinodular architecture with cellular nodules separated by fibrous septa, containing a mixture of mononuclear and multinucleated osteoclast-like giant cells.
- Ancillary: Immunohistochemistry is not helpful, and diagnostic molecular pathology is not clinically relevant for giant cell tumour of soft tissue.
Reference Gallery:
Giant cell tumour of soft tissue. Giant cell tumour of soft tissue is composed of nodules of osteoclast-like multinucleated giant cells intermixed with ovoid mononuclear cells.
Giant cell tumour of soft tissue. Giant cell tumour of soft tissue shows a characteristic multinodular architecture where clusters of osteoclast-like multinucleated giant cells are often separated by fibrous septa. Metaplastic bone formation is also commonly observed (bottom).
Giant cell tumour of soft tissue. Aneurysmal bone cyst–like changes can occur in giant cell tumour of soft tissue.
Giant cell tumour of soft tissue. The cellular nodules contain a mixture of round/oval mononuclear and multinucleated osteoclast-like giant cells.

Q: In addition to its classic cellular nodules, Giant Cell Tumor of Soft Tissue frequently exhibits metaplastic bone formation and [...]-like changes.
Giant cell tumour of soft tissue. Giant cell tumour of soft tissue shows a characteristic multinodular architecture where clusters of osteoclast-like multinucleated giant cells are often separated by fibrous septa. Metaplastic bone formation is also commonly observed (bottom).
Giant cell tumour of soft tissue. Aneurysmal bone cyst–like changes can occur in giant cell tumour of soft tissue.
A: aneurysmal bone cyst
Back Extra: Giant Cell Tumour of Soft Tissue
- Clinical: Giant cell tumour of soft tissue usually presents as a painless growing mass with an average duration of 6 months, and is most common in the fifth decade of life.
- Micro: The tumour displays a multinodular architecture with cellular nodules separated by fibrous septa, containing a mixture of mononuclear and multinucleated osteoclast-like giant cells.
- Ancillary: Immunohistochemistry is not helpful, and diagnostic molecular pathology is not clinically relevant for giant cell tumour of soft tissue.
Reference Gallery:
Giant cell tumour of soft tissue. Giant cell tumour of soft tissue is composed of nodules of osteoclast-like multinucleated giant cells intermixed with ovoid mononuclear cells.
Giant cell tumour of soft tissue. Giant cell tumour of soft tissue shows a characteristic multinodular architecture where clusters of osteoclast-like multinucleated giant cells are often separated by fibrous septa. Metaplastic bone formation is also commonly observed (bottom).
Giant cell tumour of soft tissue. Aneurysmal bone cyst–like changes can occur in giant cell tumour of soft tissue.
Giant cell tumour of soft tissue. The cellular nodules contain a mixture of round/oval mononuclear and multinucleated osteoclast-like giant cells.

Q: A superficial, painless mass presenting with a multinodular proliferation of ovoid mononuclear cells intermixed with numerous multinucleated osteoclast-like giant cells is characteristic of [...].
Giant cell tumour of soft tissue. Giant cell tumour of soft tissue is composed of nodules of osteoclast-like multinucleated giant cells intermixed with ovoid mononuclear cells.
A: Giant Cell Tumor of Soft Tissue
Back Extra: Giant Cell Tumour of Soft Tissue
- Clinical: Giant cell tumour of soft tissue usually presents as a painless growing mass with an average duration of 6 months, and is most common in the fifth decade of life.
- Micro: The tumour displays a multinodular architecture with cellular nodules separated by fibrous septa, containing a mixture of mononuclear and multinucleated osteoclast-like giant cells.
- Ancillary: Immunohistochemistry is not helpful, and diagnostic molecular pathology is not clinically relevant for giant cell tumour of soft tissue.
Reference Gallery:
Giant cell tumour of soft tissue. Giant cell tumour of soft tissue is composed of nodules of osteoclast-like multinucleated giant cells intermixed with ovoid mononuclear cells.
Giant cell tumour of soft tissue. Giant cell tumour of soft tissue shows a characteristic multinodular architecture where clusters of osteoclast-like multinucleated giant cells are often separated by fibrous septa. Metaplastic bone formation is also commonly observed (bottom).
Giant cell tumour of soft tissue. Aneurysmal bone cyst–like changes can occur in giant cell tumour of soft tissue.
Giant cell tumour of soft tissue. The cellular nodules contain a mixture of round/oval mononuclear and multinucleated osteoclast-like giant cells.

Q: Microscopically, the cytologically bland spindle cells of a Gastrointestinal Stromal Tumor frequently exhibit distinctive [...].
Gastrointestinal stromal tumour. Gastrointestinal stromal tumours are often composed of cytologically bland spindle cells that may feature distinctive perinuclear vacuolization.
A: perinuclear vacuolization
Back Extra: Gastrointestinal Stromal Tumour
- Clinical: Gastrointestinal stromal tumours (GISTs) commonly present with vague abdominal symptoms, tumour perforation, and metastasis to the liver.
- Micro: GISTs exhibit a broad morphological spectrum, including spindle cell, epithelioid, and mixed patterns, with distinctive perinuclear vacuolization in some cases.
- Ancillary: Immunohistochemistry is crucial for diagnosing GISTs, with strong and diffuse KIT (CD117) and ANO1/DOG1 expression, and loss of SDHB in SDH-deficient GISTs.
Reference Gallery:
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour shows a multinodular growth pattern through the wall of the stomach.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Muscularis propria separates tumour nodules.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour shows epithelioid morphology. Note the uniform nuclei and cytoplasmic vacuoles.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour cells show loss of staining for SDHB. Endothelial cells serve as an internal positive control.
Gastrointestinal stromal tumour, epithelioid type. This tumour harbours a PDGFRA mutation. Note the round nuclei and abundant eosinophilic cytoplasm.
Gastrointestinal stromal tumour, epithelioid type. PDGFRA-mutant gastrointestinal stromal tumours often show limited expression of KIT by immunohistochemistry (or are entirely KIT-negative).
Gastrointestinal stromal tumour, epithelioid type. Immunohistochemistry for ANO1/DOG1 is helpful to confirm the diagnosis of PDGFRA-mutant gastrointestinal stromal tumour.
Gastrointestinal stromal tumour, epithelioid type. PDGFRA-mutant gastrointestinal stromal tumours typically show strong and diffuse expression of PDGFRA.
Gastrointestinal stromal tumour. Gross image of localized gastric gastrointestinal stromal tumour. Ulceration of the gastric mucosa is present.
Gastrointestinal stromal tumour. Gross image of metastatic gastrointestinal stromal tumour to the liver. The cut surface features areas of haemorrhage and necrosis.
Gastrointestinal stromal tumour. Gastrointestinal stromal tumours are often composed of cytologically bland spindle cells that may feature distinctive perinuclear vacuolization.
Gastrointestinal stromal tumour. Rarely, gastrointestinal stromal tumour may feature a high-grade morphology that is associated with high mitotic count.

Q: A highly sensitive immunohistochemical marker used to confirm the diagnosis of a Gastrointestinal Stromal Tumor, which is especially helpful in PDGFRA-mutated cases that are negative for KIT (CD117), is [...].
Gastrointestinal stromal tumour, epithelioid type. PDGFRA-mutant gastrointestinal stromal tumours often show limited expression of KIT by immunohistochemistry (or are entirely KIT-negative).
Gastrointestinal stromal tumour, epithelioid type. Immunohistochemistry for ANO1/DOG1 is helpful to confirm the diagnosis of PDGFRA-mutant gastrointestinal stromal tumour.
A: ANO1/DOG1
Back Extra: Gastrointestinal Stromal Tumour
- Clinical: Gastrointestinal stromal tumours (GISTs) commonly present with vague abdominal symptoms, tumour perforation, and metastasis to the liver.
- Micro: GISTs exhibit a broad morphological spectrum, including spindle cell, epithelioid, and mixed patterns, with distinctive perinuclear vacuolization in some cases.
- Ancillary: Immunohistochemistry is crucial for diagnosing GISTs, with strong and diffuse KIT (CD117) and ANO1/DOG1 expression, and loss of SDHB in SDH-deficient GISTs.
Reference Gallery:
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour shows a multinodular growth pattern through the wall of the stomach.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Muscularis propria separates tumour nodules.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour shows epithelioid morphology. Note the uniform nuclei and cytoplasmic vacuoles.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour cells show loss of staining for SDHB. Endothelial cells serve as an internal positive control.
Gastrointestinal stromal tumour, epithelioid type. This tumour harbours a PDGFRA mutation. Note the round nuclei and abundant eosinophilic cytoplasm.
Gastrointestinal stromal tumour, epithelioid type. PDGFRA-mutant gastrointestinal stromal tumours often show limited expression of KIT by immunohistochemistry (or are entirely KIT-negative).
Gastrointestinal stromal tumour, epithelioid type. Immunohistochemistry for ANO1/DOG1 is helpful to confirm the diagnosis of PDGFRA-mutant gastrointestinal stromal tumour.
Gastrointestinal stromal tumour, epithelioid type. PDGFRA-mutant gastrointestinal stromal tumours typically show strong and diffuse expression of PDGFRA.
Gastrointestinal stromal tumour. Gross image of localized gastric gastrointestinal stromal tumour. Ulceration of the gastric mucosa is present.
Gastrointestinal stromal tumour. Gross image of metastatic gastrointestinal stromal tumour to the liver. The cut surface features areas of haemorrhage and necrosis.
Gastrointestinal stromal tumour. Gastrointestinal stromal tumours are often composed of cytologically bland spindle cells that may feature distinctive perinuclear vacuolization.
Gastrointestinal stromal tumour. Rarely, gastrointestinal stromal tumour may feature a high-grade morphology that is associated with high mitotic count.

Q: A specific subset of Gastrointestinal Stromal Tumor characterized by a multinodular growth pattern and uniform epithelioid morphology is defined by the immunohistochemical loss of [...].
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour shows a multinodular growth pattern through the wall of the stomach.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour cells show loss of staining for SDHB. Endothelial cells serve as an internal positive control.
A: SDHB
Back Extra: Gastrointestinal Stromal Tumour
- Clinical: Gastrointestinal stromal tumours (GISTs) commonly present with vague abdominal symptoms, tumour perforation, and metastasis to the liver.
- Micro: GISTs exhibit a broad morphological spectrum, including spindle cell, epithelioid, and mixed patterns, with distinctive perinuclear vacuolization in some cases.
- Ancillary: Immunohistochemistry is crucial for diagnosing GISTs, with strong and diffuse KIT (CD117) and ANO1/DOG1 expression, and loss of SDHB in SDH-deficient GISTs.
Reference Gallery:
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour shows a multinodular growth pattern through the wall of the stomach.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Muscularis propria separates tumour nodules.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour shows epithelioid morphology. Note the uniform nuclei and cytoplasmic vacuoles.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumour cells show loss of staining for SDHB. Endothelial cells serve as an internal positive control.
Gastrointestinal stromal tumour, epithelioid type. This tumour harbours a PDGFRA mutation. Note the round nuclei and abundant eosinophilic cytoplasm.
Gastrointestinal stromal tumour, epithelioid type. PDGFRA-mutant gastrointestinal stromal tumours often show limited expression of KIT by immunohistochemistry (or are entirely KIT-negative).
Gastrointestinal stromal tumour, epithelioid type. Immunohistochemistry for ANO1/DOG1 is helpful to confirm the diagnosis of PDGFRA-mutant gastrointestinal stromal tumour.
Gastrointestinal stromal tumour, epithelioid type. PDGFRA-mutant gastrointestinal stromal tumours typically show strong and diffuse expression of PDGFRA.
Gastrointestinal stromal tumour. Gross image of localized gastric gastrointestinal stromal tumour. Ulceration of the gastric mucosa is present.
Gastrointestinal stromal tumour. Gross image of metastatic gastrointestinal stromal tumour to the liver. The cut surface features areas of haemorrhage and necrosis.
Gastrointestinal stromal tumour. Gastrointestinal stromal tumours are often composed of cytologically bland spindle cells that may feature distinctive perinuclear vacuolization.
Gastrointestinal stromal tumour. Rarely, gastrointestinal stromal tumour may feature a high-grade morphology that is associated with high mitotic count.

Q: Histologically, Ischaemic Fasciitis is characterized by a distinct zonal architecture with a central area of [...] surrounded by a granulation tissue–like vascular proliferation.
Ischaemic fasciitis. Scanning magnification showing a distinct zonal appearance with central area of fibrinoid degeneration/necrosis with pseudocystic changes, surrounded by granulation tissue–like vascular proliferation.
A: fibrinoid necrosis
Back Extra: Ischaemic Fasciitis
- Clinical: Ischaemic fasciitis is a painless mass that primarily affects elderly patients, often associated with immobility or debilitation.
- Micro: The lesion shows a distinct zonal appearance with a central area of fibrinoid degeneration/necrosis surrounded by a granulation tissue–like vascular proliferation.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of ischaemic fasciitis.
Reference Gallery:
Ischaemic fasciitis. Scanning magnification showing a distinct zonal appearance with central area of fibrinoid degeneration/necrosis with pseudocystic changes, surrounded by granulation tissue–like vascular proliferation.
Ischaemic fasciitis. Ischaemic fasciitis with a vascular proliferation showing endothelial cells with reactive hyperchromatic nuclei (no endothelial multilayering), admixed with a reactive fibroblastic/myofibroblastic proliferation with extravasated erythrocytes.
Ischaemic fasciitis. Ischaemic fasciitis with focally myxoid stroma, infarcted fat, hyalinized vessel walls, and reactive fibroblasts/myofibroblasts with a ganglion cell–like appearance.
Ischaemic fasciitis. Ischaemic fasciitis with polygonal fibroblasts showing enlarged nuclei, prominent nucleoli, and amphophilic cytoplasm, similar to ganglion-like cells in proliferative fasciitis.

Q: In Ischaemic Fasciitis, the reactive fibroblasts and myofibroblasts often exhibit enlarged nuclei, prominent nucleoli, and amphophilic cytoplasm, giving them a characteristic [...] appearance.
Ischaemic fasciitis. Ischaemic fasciitis with focally myxoid stroma, infarcted fat, hyalinized vessel walls, and reactive fibroblasts/myofibroblasts with a ganglion cell–like appearance.
Ischaemic fasciitis. Ischaemic fasciitis with polygonal fibroblasts showing enlarged nuclei, prominent nucleoli, and amphophilic cytoplasm, similar to ganglion-like cells in proliferative fasciitis.
A: ganglion-like
Back Extra: Ischaemic Fasciitis
- Clinical: Ischaemic fasciitis is a painless mass that primarily affects elderly patients, often associated with immobility or debilitation.
- Micro: The lesion shows a distinct zonal appearance with a central area of fibrinoid degeneration/necrosis surrounded by a granulation tissue–like vascular proliferation.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of ischaemic fasciitis.
Reference Gallery:
Ischaemic fasciitis. Scanning magnification showing a distinct zonal appearance with central area of fibrinoid degeneration/necrosis with pseudocystic changes, surrounded by granulation tissue–like vascular proliferation.
Ischaemic fasciitis. Ischaemic fasciitis with a vascular proliferation showing endothelial cells with reactive hyperchromatic nuclei (no endothelial multilayering), admixed with a reactive fibroblastic/myofibroblastic proliferation with extravasated erythrocytes.
Ischaemic fasciitis. Ischaemic fasciitis with focally myxoid stroma, infarcted fat, hyalinized vessel walls, and reactive fibroblasts/myofibroblasts with a ganglion cell–like appearance.
Ischaemic fasciitis. Ischaemic fasciitis with polygonal fibroblasts showing enlarged nuclei, prominent nucleoli, and amphophilic cytoplasm, similar to ganglion-like cells in proliferative fasciitis.

Q: The pathognomonic radiologic and histologic feature of Myositis Ossificans and Fibro-osseous Pseudotumour of Digits is a distinct [...], featuring a hypercellular center that is surrounded by progressively maturing woven bone.
Myositis ossificans. Radiograph of a round mass in the soft tissues of the wrist showing a fine cloud-like pattern of mineralization, densest at the periphery.
Myositis ossificans. Zonation pattern with focally cystic hypercellular centre surrounded by progressively maturing woven bone.
A: zonal architecture
Back Extra: Myositis Ossificans and Fibro-osseous Pseudotumour of Digits
- Clinical: Myositis ossificans and fibro-osseous pseudotumour of digits present with rapid growth and evolve over time, initially showing swelling and pain, and later becoming hard and well demarcated.
- Micro: Myositis ossificans is characterized by a zonal architecture with a hypercellular centre and progressively maturing woven bone peripherally.
- Ancillary: Molecular studies such as USP6 rearrangement can be useful in distinguishing myositis ossificans from malignant lesions like extraskeletal osteosarcoma.
Reference Gallery:
Myositis ossificans. Radiograph of a round mass in the soft tissues of the wrist showing a fine cloud-like pattern of mineralization, densest at the periphery.
Myositis ossificans. Well-circumscribed tan haemorrhagic mass.
Myositis ossificans. Zonation pattern with focally cystic hypercellular centre surrounded by progressively maturing woven bone.
Myositis ossificans. Fascicles of plump spindle cells with elongate nuclei that are mitotically active. The stroma is myxocollagenous with scattered extravasated red blood cells. Histological resemblance to nodular fasciitis is evident.
Myositis ossificans. Poorly formed woven bone associated with osteoblasts merges with matrix that is well formed and trabecular in architecture.
Myositis ossificans. Hypercellular hyaline cartilage undergoing enchondral ossification.
Fibro-osseous pseudotumour of digits. The lesion presents as a well-circumscribed subcuticular mass.

Q: The highly cellular central region of Myositis Ossificans and Fibro-osseous Pseudotumour of Digits contains mitotically active plump spindle cells within a myxocollagenous stroma and extravasated red blood cells, closely resembling [...] on histology.
Myositis ossificans. Fascicles of plump spindle cells with elongate nuclei that are mitotically active. The stroma is myxocollagenous with scattered extravasated red blood cells. Histological resemblance to nodular fasciitis is evident.
A: nodular fasciitis
Back Extra: Myositis Ossificans and Fibro-osseous Pseudotumour of Digits
- Clinical: Myositis ossificans and fibro-osseous pseudotumour of digits present with rapid growth and evolve over time, initially showing swelling and pain, and later becoming hard and well demarcated.
- Micro: Myositis ossificans is characterized by a zonal architecture with a hypercellular centre and progressively maturing woven bone peripherally.
- Ancillary: Molecular studies such as USP6 rearrangement can be useful in distinguishing myositis ossificans from malignant lesions like extraskeletal osteosarcoma.
Reference Gallery:
Myositis ossificans. Radiograph of a round mass in the soft tissues of the wrist showing a fine cloud-like pattern of mineralization, densest at the periphery.
Myositis ossificans. Well-circumscribed tan haemorrhagic mass.
Myositis ossificans. Zonation pattern with focally cystic hypercellular centre surrounded by progressively maturing woven bone.
Myositis ossificans. Fascicles of plump spindle cells with elongate nuclei that are mitotically active. The stroma is myxocollagenous with scattered extravasated red blood cells. Histological resemblance to nodular fasciitis is evident.
Myositis ossificans. Poorly formed woven bone associated with osteoblasts merges with matrix that is well formed and trabecular in architecture.
Myositis ossificans. Hypercellular hyaline cartilage undergoing enchondral ossification.
Fibro-osseous pseudotumour of digits. The lesion presents as a well-circumscribed subcuticular mass.

Q: In Proliferative Fasciitis and Proliferative Myositis, the histological hallmark is the admixture of plump myofibroblastic spindle cells with distinctive, large [...] cells possessing prominent nucleoli.
Proliferative fasciitis. Ganglion-like cells at higher power.
Proliferative myositis. Details of the cytological features of the ganglion-like cells with prominent nucleoli.
A: ganglion-like
Back Extra: Proliferative Fasciitis and Proliferative Myositis
- Clinical: Both proliferative fasciitis and proliferative myositis grow rapidly and are usually excised within 2 months from the time they are first noted.
- Micro: The lesions contain plump myofibroblastic/fibroblastic spindle cells and large ganglion-like cells with prominent nucleoli.
- Ancillary: The spindle cells in proliferative fasciitis and myositis usually express SMA and MSA but are negative for desmin.
Reference Gallery:
Proliferative fasciitis. Ganglion-like cells are admixed with spindle cells and lymphocytes in a loose myxoid matrix.
Proliferative fasciitis. Ganglion-like cells at higher power.
Proliferative myositis. Note the spindle cells. Ganglion-like cells sporting amphophilic cytoplasm are admixed.
Proliferative myositis. Details of the cytological features of the ganglion-like cells with prominent nucleoli.

Q: A rapidly growing soft tissue lesion characterized microscopically by plump spindle cells and prominent ganglion-like cells with amphophilic cytoplasm in a loose, sometimes myxoid matrix is highly diagnostic of [...].
Proliferative fasciitis. Ganglion-like cells are admixed with spindle cells and lymphocytes in a loose myxoid matrix.
Proliferative myositis. Note the spindle cells. Ganglion-like cells sporting amphophilic cytoplasm are admixed.
A: Proliferative Fasciitis and Proliferative Myositis
Back Extra: Proliferative Fasciitis and Proliferative Myositis
- Clinical: Both proliferative fasciitis and proliferative myositis grow rapidly and are usually excised within 2 months from the time they are first noted.
- Micro: The lesions contain plump myofibroblastic/fibroblastic spindle cells and large ganglion-like cells with prominent nucleoli.
- Ancillary: The spindle cells in proliferative fasciitis and myositis usually express SMA and MSA but are negative for desmin.
Reference Gallery:
Proliferative fasciitis. Ganglion-like cells are admixed with spindle cells and lymphocytes in a loose myxoid matrix.
Proliferative fasciitis. Ganglion-like cells at higher power.
Proliferative myositis. Note the spindle cells. Ganglion-like cells sporting amphophilic cytoplasm are admixed.
Proliferative myositis. Details of the cytological features of the ganglion-like cells with prominent nucleoli.

Q: Microscopically, a Benign Triton Tumor / Neuromuscular Choristoma is uniquely characterized by haphazardly arranged bundles of mature [...] with cross-striations intercalated between native intraneural elements.
Neuromuscular choristoma. Cross-section showing several peripheral nerve fascicles with endoneurial mature skeletal muscle fibres intertwined with native neural elements.
Neuromuscular choristoma. Longitudinal section showing several peripheral nerve fascicles with endoneurial mature skeletal muscle fibres highlighted by desmin positivity, intertwined with native neural elements.
A: skeletal muscle
Back Extra: Benign Triton Tumour / Neuromuscular Choristoma
- Clinical: Patients often present with progressive pain or features of peripheral neuropathy/plexopathy, with up to 80% developing desmoid fibromatosis post-surgery.
- Micro: Haphazardly arranged bundles of mature skeletal muscle with cross-striations are intercalated between intraneural elements, with the myogenic component expressing desmin and NFP-positive axons surrounded by S100-positive Schwann cells.
- Ancillary: The presence of CTNNB1 exon 3 (p.Thr41Ala and p.Ser45Phe) mutations supports the diagnosis of benign triton tumour / NMC with or without associated desmoid fibromatosis.
Reference Gallery:
Neuromuscular choristoma. Coronal T1-weighted MRI showing a fusiform mass of the left brachial plexus with signal density resembling that of adjacent skeletal muscle.
Neuromuscular choristoma-fibromatosis. Postcontrast MRI of the thigh showing an enhancing and invasive mass diagnosed as a desmoid-type fibromatosis on histopathology. This was seen in association with a neuromuscular choristoma of the sciatic nerve.
Neuromuscular choristoma-fibromatosis. Gross pathology from the resection specimen of the patient shown in <<#2615>>Fig. #2615. On cut surface, the desmoid showed a firm, irregular, glistening greyish-white mass that invades into adjacent skeletal muscle.
Neuromuscular choristoma. Cross-section showing several peripheral nerve fascicles with endoneurial mature skeletal muscle fibres intertwined with native neural elements.
Neuromuscular choristoma. Longitudinal section showing several peripheral nerve fascicles with endoneurial mature skeletal muscle fibres highlighted by desmin positivity, intertwined with native neural elements.
Neuromuscular choristoma. Cross-section highlighting axons with NFP immunostaining.
Neuromuscular choristoma. Tangential section with small involved peripheral nerve fascicles surrounded by perineurial cells, the latter highlighted with an EMA immunostain.

Q: A striking clinical feature of a Benign Triton Tumor / Neuromuscular Choristoma is that up to 80% of patients will develop an associated [...] following surgical intervention, which presents grossly as a firm, irregular, gray-white infiltrating mass.
Neuromuscular choristoma-fibromatosis. Postcontrast MRI of the thigh showing an enhancing and invasive mass diagnosed as a desmoid-type fibromatosis on histopathology. This was seen in association with a neuromuscular choristoma of the sciatic nerve.
Neuromuscular choristoma-fibromatosis. Gross pathology from the resection specimen of the patient shown in <<#2615>>Fig. #2615. On cut surface, the desmoid showed a firm, irregular, glistening greyish-white mass that invades into adjacent skeletal muscle.
A: desmoid fibromatosis
Back Extra: Benign Triton Tumour / Neuromuscular Choristoma
- Clinical: Patients often present with progressive pain or features of peripheral neuropathy/plexopathy, with up to 80% developing desmoid fibromatosis post-surgery.
- Micro: Haphazardly arranged bundles of mature skeletal muscle with cross-striations are intercalated between intraneural elements, with the myogenic component expressing desmin and NFP-positive axons surrounded by S100-positive Schwann cells.
- Ancillary: The presence of CTNNB1 exon 3 (p.Thr41Ala and p.Ser45Phe) mutations supports the diagnosis of benign triton tumour / NMC with or without associated desmoid fibromatosis.
Reference Gallery:
Neuromuscular choristoma. Coronal T1-weighted MRI showing a fusiform mass of the left brachial plexus with signal density resembling that of adjacent skeletal muscle.
Neuromuscular choristoma-fibromatosis. Postcontrast MRI of the thigh showing an enhancing and invasive mass diagnosed as a desmoid-type fibromatosis on histopathology. This was seen in association with a neuromuscular choristoma of the sciatic nerve.
Neuromuscular choristoma-fibromatosis. Gross pathology from the resection specimen of the patient shown in <<#2615>>Fig. #2615. On cut surface, the desmoid showed a firm, irregular, glistening greyish-white mass that invades into adjacent skeletal muscle.
Neuromuscular choristoma. Cross-section showing several peripheral nerve fascicles with endoneurial mature skeletal muscle fibres intertwined with native neural elements.
Neuromuscular choristoma. Longitudinal section showing several peripheral nerve fascicles with endoneurial mature skeletal muscle fibres highlighted by desmin positivity, intertwined with native neural elements.
Neuromuscular choristoma. Cross-section highlighting axons with NFP immunostaining.
Neuromuscular choristoma. Tangential section with small involved peripheral nerve fascicles surrounded by perineurial cells, the latter highlighted with an EMA immunostain.

Q: A superficial soft tissue tumor often found on the fingers, characterized histologically by a multinodular growth pattern with an abundant myxoid matrix, a fibrous rind, and neoplastic Schwann cells forming cords or syncytial-like aggregates, is known as [...].
Dermal nerve sheath myxoma. <<#13517>>Fig. #13517, <<#13518>>Fig. #13518, and this one show low- and intermediate-power views. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. <<#13516>>Fig. #13516, <<#13518>>Fig. #13518, and this one show low- and intermediate-power views. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. <<#13516>>Fig. #13516, <<#13517>>Fig. #13517, and this one show low- and intermediate-power views. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
A: Dermal Nerve Sheath Myxoma
Back Extra: Dermal Nerve Sheath Myxoma
- Clinical: Dermal nerve sheath myxomas typically present as small, superficial, slow-growing masses, often asymptomatic, but some may be painful. They are most common in the fingers and lower extremities.
- Micro: Tumours are characterized by a multinodular growth pattern with an abundant myxoid matrix and neoplastic Schwann cells arranged in cords and syncytial-like aggregates. Some cells may have a ring-like appearance.
- Ancillary: Neoplastic Schwann cells are diffusely immunoreactive for S100, and most cases show moderate to diffuse reactivity for GFAP and CD57.
Reference Gallery:
Dermal nerve sheath myxoma. <<#13517>>Fig. #13517, <<#13518>>Fig. #13518, and this one show low- and intermediate-power views. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. <<#13516>>Fig. #13516, <<#13518>>Fig. #13518, and this one show low- and intermediate-power views. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. <<#13516>>Fig. #13516, <<#13517>>Fig. #13517, and this one show low- and intermediate-power views. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. The neoplastic Schwann cells express S100.

Q: In Dermal Nerve Sheath Myxoma, the neoplastic cells are of Schwannian origin and characteristically demonstrate diffuse immunohistochemical reactivity for [...].
Dermal nerve sheath myxoma. The neoplastic Schwann cells express S100.
A: S100
Back Extra: Dermal Nerve Sheath Myxoma
- Clinical: Dermal nerve sheath myxomas typically present as small, superficial, slow-growing masses, often asymptomatic, but some may be painful. They are most common in the fingers and lower extremities.
- Micro: Tumours are characterized by a multinodular growth pattern with an abundant myxoid matrix and neoplastic Schwann cells arranged in cords and syncytial-like aggregates. Some cells may have a ring-like appearance.
- Ancillary: Neoplastic Schwann cells are diffusely immunoreactive for S100, and most cases show moderate to diffuse reactivity for GFAP and CD57.
Reference Gallery:
Dermal nerve sheath myxoma. <<#13517>>Fig. #13517, <<#13518>>Fig. #13518, and this one show low- and intermediate-power views. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. <<#13516>>Fig. #13516, <<#13518>>Fig. #13518, and this one show low- and intermediate-power views. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. <<#13516>>Fig. #13516, <<#13517>>Fig. #13517, and this one show low- and intermediate-power views. Note the multinodularity, the rind of fibrous tissue around the nodules, and the abundant myxoid matrix. The neoplastic Schwann cells are arranged in cords and syncytial-like aggregates. Some have a ring-like appearance and resemble fat cells.
Dermal nerve sheath myxoma. The neoplastic Schwann cells express S100.

Q: In mucosal biopsies, particularly of the tongue, granular cell tumor classically induces prominent [...] in the overlying squamous epithelium, which can mimic invasive carcinoma.
Granular cell tumour. This biopsy of a tongue lesion shows pseudoepitheliomatous hyperplasia, mimicking invasive carcinoma. Note the sheets of granular cell tumour cells with extensive granular cytoplasm surrounding the nests of hyperplastic squamous epithelium.
A: pseudoepitheliomatous hyperplasia
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours are more prevalent in males and African-Americans, with a peak incidence in the fourth to sixth decades of life.
- Micro: The tumour is composed of sheets, nests, and trabeculae of large, monotonous epithelioid to polygonal cells with eosinophilic, granular cytoplasm.
- Ancillary: Granular cell tumours are generally reactive for S100, SOX10, and CD68, and often show loss-of-function mutations in ATP6AP1 and ATP6AP2.
Reference Gallery:
Granular cell tumour. This biopsy of a tongue lesion shows pseudoepitheliomatous hyperplasia, mimicking invasive carcinoma. Note the sheets of granular cell tumour cells with extensive granular cytoplasm surrounding the nests of hyperplastic squamous epithelium.
Granular cell tumour. As seen here, S100 immunohistochemistry is diffusely and strongly positive in granular cell tumour.
Malignant granular cell tumour. This malignant granular cell tumour shows cytological pleomorphism and extensive mitotic activity, including atypical mitotic figures.
Granular cell tumour. The squamous epithelium overlying the tumour shows basal cell hyperplasia.
Granular cell tumour. The tumour is composed of polygonal cells with hyperchromatic nuclei and abundant granular eosinophilic cytoplasm. Note the occasional cells with degenerative nuclear atypia.

Q: By immunohistochemistry, a granular cell tumor is typically diffusely and strongly positive for the neural crest marker [...] (along with SOX10 and CD68).
Granular cell tumour. As seen here, S100 immunohistochemistry is diffusely and strongly positive in granular cell tumour.
A: S100
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours are more prevalent in males and African-Americans, with a peak incidence in the fourth to sixth decades of life.
- Micro: The tumour is composed of sheets, nests, and trabeculae of large, monotonous epithelioid to polygonal cells with eosinophilic, granular cytoplasm.
- Ancillary: Granular cell tumours are generally reactive for S100, SOX10, and CD68, and often show loss-of-function mutations in ATP6AP1 and ATP6AP2.
Reference Gallery:
Granular cell tumour. This biopsy of a tongue lesion shows pseudoepitheliomatous hyperplasia, mimicking invasive carcinoma. Note the sheets of granular cell tumour cells with extensive granular cytoplasm surrounding the nests of hyperplastic squamous epithelium.
Granular cell tumour. As seen here, S100 immunohistochemistry is diffusely and strongly positive in granular cell tumour.
Malignant granular cell tumour. This malignant granular cell tumour shows cytological pleomorphism and extensive mitotic activity, including atypical mitotic figures.
Granular cell tumour. The squamous epithelium overlying the tumour shows basal cell hyperplasia.
Granular cell tumour. The tumour is composed of polygonal cells with hyperchromatic nuclei and abundant granular eosinophilic cytoplasm. Note the occasional cells with degenerative nuclear atypia.

Q: The characteristic morphologic hallmark of a [...] is the presence of nests and sheets of large, monotonous polygonal cells with abundant, eosinophilic, granular cytoplasm.
Granular cell tumour. The tumour is composed of polygonal cells with hyperchromatic nuclei and abundant granular eosinophilic cytoplasm. Note the occasional cells with degenerative nuclear atypia.
A: granular cell tumor
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours are more prevalent in males and African-Americans, with a peak incidence in the fourth to sixth decades of life.
- Micro: The tumour is composed of sheets, nests, and trabeculae of large, monotonous epithelioid to polygonal cells with eosinophilic, granular cytoplasm.
- Ancillary: Granular cell tumours are generally reactive for S100, SOX10, and CD68, and often show loss-of-function mutations in ATP6AP1 and ATP6AP2.
Reference Gallery:
Granular cell tumour. This biopsy of a tongue lesion shows pseudoepitheliomatous hyperplasia, mimicking invasive carcinoma. Note the sheets of granular cell tumour cells with extensive granular cytoplasm surrounding the nests of hyperplastic squamous epithelium.
Granular cell tumour. As seen here, S100 immunohistochemistry is diffusely and strongly positive in granular cell tumour.
Malignant granular cell tumour. This malignant granular cell tumour shows cytological pleomorphism and extensive mitotic activity, including atypical mitotic figures.
Granular cell tumour. The squamous epithelium overlying the tumour shows basal cell hyperplasia.
Granular cell tumour. The tumour is composed of polygonal cells with hyperchromatic nuclei and abundant granular eosinophilic cytoplasm. Note the occasional cells with degenerative nuclear atypia.

Q: The neurofibroma/schwannoma variant of Hybrid Nerve Sheath Tumor classically features a loose, hypocellular background of neurofibroma containing distinct, highly cellular [...].
Hybrid schwannoma/neurofibroma. Hybrid schwannoma/neurofibroma with areas of solid Schwann cell proliferation and loose areas of neurofibroma appearance.
Hybrid schwannoma/neurofibroma. S100 stain showing diffuse staining in the solid Schwann cell nodule and mixed population of cells (S100-positive and S100-negative) in surrounding loose areas.
Hybrid schwannoma/neurofibroma. Solid nodule of Schwann cell proliferation surrounded by loose hypocellular tumour.
A: schwannomatous nodules
Back Extra: Hybrid Nerve Sheath Tumour
- Clinical: Hybrid Nerve Sheath Tumours present most often as painless masses in subcutaneous tissue or dermis, with potential for pain or neurological deficit if large peripheral nerves or spinal nerves are involved.
- Micro: Hybrid schwannoma/perineurioma shows a storiform or fascicular growth with alternating Schwann cells and perineurial cells, while hybrid neurofibroma/schwannoma contains schwannomatous nodules within a neurofibroma.
- Ancillary: Immunohistochemistry is crucial for distinguishing the components, with S100-positive Schwann cells and EMA-positive perineurial cells.
Reference Gallery:
Hybrid schwannoma/neurofibroma. Hybrid schwannoma/neurofibroma with areas of solid Schwann cell proliferation and loose areas of neurofibroma appearance.
Hybrid schwannoma/neurofibroma. S100 stain showing diffuse staining in the solid Schwann cell nodule and mixed population of cells (S100-positive and S100-negative) in surrounding loose areas.
Hybrid schwannoma/neurofibroma. Solid nodule of Schwann cell proliferation surrounded by loose hypocellular tumour.
Hybrid schwannoma/perineurioma. The tumour shows a storiform architecture, similar to perineurioma of soft tissue.
Hybrid schwannoma/perineurioma. Many of the tumour cells contain plump, tapering nuclei and eosinophilic cytoplasm, typical of Schwann cells. The perineurial cell component is often inconspicuous.
Hybrid schwannoma/perineurioma. Double immunolabelling for S100 (red) and EMA (brown) highlights alternating Schwann cells and perineurial cells, respectively.

Q: The schwannoma/perineurioma variant of Hybrid Nerve Sheath Tumor typically shows a storiform architecture with alternating S100-positive Schwann cells and perineurial cells that characteristically stain positive for [...].
Hybrid schwannoma/perineurioma. The tumour shows a storiform architecture, similar to perineurioma of soft tissue.
Hybrid schwannoma/perineurioma. Many of the tumour cells contain plump, tapering nuclei and eosinophilic cytoplasm, typical of Schwann cells. The perineurial cell component is often inconspicuous.
Hybrid schwannoma/perineurioma. Double immunolabelling for S100 (red) and EMA (brown) highlights alternating Schwann cells and perineurial cells, respectively.
A: EMA
Back Extra: Hybrid Nerve Sheath Tumour
- Clinical: Hybrid Nerve Sheath Tumours present most often as painless masses in subcutaneous tissue or dermis, with potential for pain or neurological deficit if large peripheral nerves or spinal nerves are involved.
- Micro: Hybrid schwannoma/perineurioma shows a storiform or fascicular growth with alternating Schwann cells and perineurial cells, while hybrid neurofibroma/schwannoma contains schwannomatous nodules within a neurofibroma.
- Ancillary: Immunohistochemistry is crucial for distinguishing the components, with S100-positive Schwann cells and EMA-positive perineurial cells.
Reference Gallery:
Hybrid schwannoma/neurofibroma. Hybrid schwannoma/neurofibroma with areas of solid Schwann cell proliferation and loose areas of neurofibroma appearance.
Hybrid schwannoma/neurofibroma. S100 stain showing diffuse staining in the solid Schwann cell nodule and mixed population of cells (S100-positive and S100-negative) in surrounding loose areas.
Hybrid schwannoma/neurofibroma. Solid nodule of Schwann cell proliferation surrounded by loose hypocellular tumour.
Hybrid schwannoma/perineurioma. The tumour shows a storiform architecture, similar to perineurioma of soft tissue.
Hybrid schwannoma/perineurioma. Many of the tumour cells contain plump, tapering nuclei and eosinophilic cytoplasm, typical of Schwann cells. The perineurial cell component is often inconspicuous.
Hybrid schwannoma/perineurioma. Double immunolabelling for S100 (red) and EMA (brown) highlights alternating Schwann cells and perineurial cells, respectively.

Q: Microscopically, a Neurofibroma features bland spindle cells with thin, wavy nuclei in a loose myxoid stroma, often with characteristic collagen bundles that resemble [...].
Neurofibroma. Loose myxoid stroma and small tumour cells with wavy nuclei and cytoplasmic processes.
Neurofibroma. Foci of collagenization resemble shredded carrots.
A: shredded carrots
Back Extra: Neurofibroma
- Clinical: Cutaneous neurofibromas are usually asymptomatic and most commonly present as a mobile soft mass. Deep tumours often present with motor or sensory symptoms in the distribution of the affected nerve.
- Micro: Neurofibromas are characterized by bland spindle cells with thin, wavy nuclei immersed in a variably loose myxoid stroma, often with collagenization resembling shredded carrots.
- Ancillary: Immunoprofile includes S100 positivity in the Schwannian cell population and CD34 highlighting the stromal component. Nuclear atypia and loss of p16 expression may suggest atypical neurofibroma or malignant transformation.
Reference Gallery:
Cellular neurofibroma. Other than hypercellularity, this neurofibroma shows no worrisome features to warrant consideration of atypical neurofibromatous neoplasm of uncertain biological potential or malignant peripheral nerve sheath tumour.
Neurofibroma. Loose myxoid stroma and small tumour cells with wavy nuclei and cytoplasmic processes.
Neurofibroma. Foci of collagenization resemble shredded carrots.
Neurofibroma. NFP immunostaining highlights entrapped axons.
Neurofibroma. A SOX10 immunostain highlights numerous neoplastic Schwann cells, whereas the non-neoplastic components in the tumour (e.g. fibroblasts, perineurial cells, mast cells) are negative.
Neurofibroma. An S100 immunostain highlights the parallel stacks of Schwann cell cytoplasm within pseudomeissnerian bodies.
Neurofibroma with atypia (ancient neurofibroma). Other than the scattered cytologically atypical cells, no worrisome features are present in this neurofibroma to warrant consideration of atypical neurofibromatous neoplasm of uncertain biological potential or malignant peripheral nerve sheath tumour.
Diffuse cutaneous neurofibroma. This example is characterized by a plaque-like pattern of growth expanding the dermis and the superficial subcutis. Note the lack of a discrete mass.
Plexiform neurofibroma. Multiple nerve fascicles are involved by this tumour, imparting a multinodular or bag-of-worms appearance at low magnification.
Massive soft tissue neurofibroma. A typical finding is a cellular component composed of cells with high N:C ratios but rare to absent mitotic activity. Pseudomeissnerian corpuscles are also common (present in upper-left corner).
Atypical neurofibromatous neoplasm of uncertain biological potential. Loss of neurofibromatous architecture and increased mitotic count.
Atypical neurofibromatous neoplasm of uncertain biological potential. A CD34 immunostain reveals the normal lattice-like pattern of positivity in the conventional neurofibroma component (left), with loss of this architectural pattern in the focus of atypical neurofibromatous neoplasm of uncertain biological potential (right).

Q: In a Neurofibroma, the neoplastic Schwann cells are positive for S100 and SOX10, while an immunostain for [...] can be used to highlight the characteristic scattered entrapped axons.
Neurofibroma. NFP immunostaining highlights entrapped axons.
Neurofibroma. A SOX10 immunostain highlights numerous neoplastic Schwann cells, whereas the non-neoplastic components in the tumour (e.g. fibroblasts, perineurial cells, mast cells) are negative.
Neurofibroma. An S100 immunostain highlights the parallel stacks of Schwann cell cytoplasm within pseudomeissnerian bodies.
A: neurofilament protein (NFP)
Back Extra: Neurofibroma
- Clinical: Cutaneous neurofibromas are usually asymptomatic and most commonly present as a mobile soft mass. Deep tumours often present with motor or sensory symptoms in the distribution of the affected nerve.
- Micro: Neurofibromas are characterized by bland spindle cells with thin, wavy nuclei immersed in a variably loose myxoid stroma, often with collagenization resembling shredded carrots.
- Ancillary: Immunoprofile includes S100 positivity in the Schwannian cell population and CD34 highlighting the stromal component. Nuclear atypia and loss of p16 expression may suggest atypical neurofibroma or malignant transformation.
Reference Gallery:
Cellular neurofibroma. Other than hypercellularity, this neurofibroma shows no worrisome features to warrant consideration of atypical neurofibromatous neoplasm of uncertain biological potential or malignant peripheral nerve sheath tumour.
Neurofibroma. Loose myxoid stroma and small tumour cells with wavy nuclei and cytoplasmic processes.
Neurofibroma. Foci of collagenization resemble shredded carrots.
Neurofibroma. NFP immunostaining highlights entrapped axons.
Neurofibroma. A SOX10 immunostain highlights numerous neoplastic Schwann cells, whereas the non-neoplastic components in the tumour (e.g. fibroblasts, perineurial cells, mast cells) are negative.
Neurofibroma. An S100 immunostain highlights the parallel stacks of Schwann cell cytoplasm within pseudomeissnerian bodies.
Neurofibroma with atypia (ancient neurofibroma). Other than the scattered cytologically atypical cells, no worrisome features are present in this neurofibroma to warrant consideration of atypical neurofibromatous neoplasm of uncertain biological potential or malignant peripheral nerve sheath tumour.
Diffuse cutaneous neurofibroma. This example is characterized by a plaque-like pattern of growth expanding the dermis and the superficial subcutis. Note the lack of a discrete mass.
Plexiform neurofibroma. Multiple nerve fascicles are involved by this tumour, imparting a multinodular or bag-of-worms appearance at low magnification.
Massive soft tissue neurofibroma. A typical finding is a cellular component composed of cells with high N:C ratios but rare to absent mitotic activity. Pseudomeissnerian corpuscles are also common (present in upper-left corner).
Atypical neurofibromatous neoplasm of uncertain biological potential. Loss of neurofibromatous architecture and increased mitotic count.
Atypical neurofibromatous neoplasm of uncertain biological potential. A CD34 immunostain reveals the normal lattice-like pattern of positivity in the conventional neurofibroma component (left), with loss of this architectural pattern in the focus of atypical neurofibromatous neoplasm of uncertain biological potential (right).

Q: The [...] variant of Neurofibroma involves multiple nerve fascicles, classically imparting a multinodular or "bag-of-worms" appearance at low magnification.
Plexiform neurofibroma. Multiple nerve fascicles are involved by this tumour, imparting a multinodular or bag-of-worms appearance at low magnification.
A: plexiform
Back Extra: Neurofibroma
- Clinical: Cutaneous neurofibromas are usually asymptomatic and most commonly present as a mobile soft mass. Deep tumours often present with motor or sensory symptoms in the distribution of the affected nerve.
- Micro: Neurofibromas are characterized by bland spindle cells with thin, wavy nuclei immersed in a variably loose myxoid stroma, often with collagenization resembling shredded carrots.
- Ancillary: Immunoprofile includes S100 positivity in the Schwannian cell population and CD34 highlighting the stromal component. Nuclear atypia and loss of p16 expression may suggest atypical neurofibroma or malignant transformation.
Reference Gallery:
Cellular neurofibroma. Other than hypercellularity, this neurofibroma shows no worrisome features to warrant consideration of atypical neurofibromatous neoplasm of uncertain biological potential or malignant peripheral nerve sheath tumour.
Neurofibroma. Loose myxoid stroma and small tumour cells with wavy nuclei and cytoplasmic processes.
Neurofibroma. Foci of collagenization resemble shredded carrots.
Neurofibroma. NFP immunostaining highlights entrapped axons.
Neurofibroma. A SOX10 immunostain highlights numerous neoplastic Schwann cells, whereas the non-neoplastic components in the tumour (e.g. fibroblasts, perineurial cells, mast cells) are negative.
Neurofibroma. An S100 immunostain highlights the parallel stacks of Schwann cell cytoplasm within pseudomeissnerian bodies.
Neurofibroma with atypia (ancient neurofibroma). Other than the scattered cytologically atypical cells, no worrisome features are present in this neurofibroma to warrant consideration of atypical neurofibromatous neoplasm of uncertain biological potential or malignant peripheral nerve sheath tumour.
Diffuse cutaneous neurofibroma. This example is characterized by a plaque-like pattern of growth expanding the dermis and the superficial subcutis. Note the lack of a discrete mass.
Plexiform neurofibroma. Multiple nerve fascicles are involved by this tumour, imparting a multinodular or bag-of-worms appearance at low magnification.
Massive soft tissue neurofibroma. A typical finding is a cellular component composed of cells with high N:C ratios but rare to absent mitotic activity. Pseudomeissnerian corpuscles are also common (present in upper-left corner).
Atypical neurofibromatous neoplasm of uncertain biological potential. Loss of neurofibromatous architecture and increased mitotic count.
Atypical neurofibromatous neoplasm of uncertain biological potential. A CD34 immunostain reveals the normal lattice-like pattern of positivity in the conventional neurofibroma component (left), with loss of this architectural pattern in the focus of atypical neurofibromatous neoplasm of uncertain biological potential (right).

Q: The typical microscopic appearance of soft tissue perineurioma features slender spindle cells arranged in a storiform or whorled growth pattern with characteristic delicate [...] cytoplasmic processes.
Perineurioma of soft tissue. The tumour shows a storiform growth pattern.
Perineurioma. The lesion shows a lamellar arrangement of elongated spindle cells with tapering nuclei in a somewhat myxoid stroma.
A: bipolar
Back Extra: Perineurioma
- Clinical: Perineuriomas of soft tissue usually present as painless masses, most commonly in the lower limbs, and are slightly more common in females than males.
- Micro: Soft tissue perineuriomas typically show a storiform or whorled growth pattern with slender spindle cells, characteristic delicate bipolar cytoplasmic processes, and a collagenous stroma.
- Ancillary: By immunohistochemistry, perineuriomas consistently express EMA and often CD34, but are negative for S100, SOX10, and GFAP.
Reference Gallery:
Perineurioma. Sclerosing perineurioma composed of cords of epithelioid cells in a dense collagenous stroma.
Perineurioma of soft tissue. The tumour shows a storiform growth pattern.
Perineurioma of soft tissue. The tumour cells contain uniform ovoid to elongated nuclei. Note the fibrillary stroma.
Perineurioma. Perivascular whorls are a typical feature. Note the collagenous stroma.
Perineurioma. The lesion shows a lamellar arrangement of elongated spindle cells with tapering nuclei in a somewhat myxoid stroma.
Perineurioma. Reticular perineurioma composed of anastomosing elongated spindle cells with a lacy architecture.
Soft tissue perineurioma. Immunohistochemical staining for EMA highlights the delicate bipolar cytoplasmic processes of the tumour cells.
Soft tissue perineurioma. Expression of CD34 is often more diffuse than that of EMA.

Q: By immunohistochemistry, the slender spindle cells of perineurioma consistently express [...] (which highlights their delicate cytoplasmic processes) and often CD34, but lack S100 and SOX10 expression.
Soft tissue perineurioma. Immunohistochemical staining for EMA highlights the delicate bipolar cytoplasmic processes of the tumour cells.
Soft tissue perineurioma. Expression of CD34 is often more diffuse than that of EMA.
A: EMA
Back Extra: Perineurioma
- Clinical: Perineuriomas of soft tissue usually present as painless masses, most commonly in the lower limbs, and are slightly more common in females than males.
- Micro: Soft tissue perineuriomas typically show a storiform or whorled growth pattern with slender spindle cells, characteristic delicate bipolar cytoplasmic processes, and a collagenous stroma.
- Ancillary: By immunohistochemistry, perineuriomas consistently express EMA and often CD34, but are negative for S100, SOX10, and GFAP.
Reference Gallery:
Perineurioma. Sclerosing perineurioma composed of cords of epithelioid cells in a dense collagenous stroma.
Perineurioma of soft tissue. The tumour shows a storiform growth pattern.
Perineurioma of soft tissue. The tumour cells contain uniform ovoid to elongated nuclei. Note the fibrillary stroma.
Perineurioma. Perivascular whorls are a typical feature. Note the collagenous stroma.
Perineurioma. The lesion shows a lamellar arrangement of elongated spindle cells with tapering nuclei in a somewhat myxoid stroma.
Perineurioma. Reticular perineurioma composed of anastomosing elongated spindle cells with a lacy architecture.
Soft tissue perineurioma. Immunohistochemical staining for EMA highlights the delicate bipolar cytoplasmic processes of the tumour cells.
Soft tissue perineurioma. Expression of CD34 is often more diffuse than that of EMA.

Q: A soft tissue tumor characterized by slender spindle cells in a storiform or whorled pattern that are consistently positive for EMA and negative for S100 is best diagnosed as a [...].
Perineurioma of soft tissue. The tumour shows a storiform growth pattern.
Perineurioma. Perivascular whorls are a typical feature. Note the collagenous stroma.
Soft tissue perineurioma. Immunohistochemical staining for EMA highlights the delicate bipolar cytoplasmic processes of the tumour cells.
A: perineurioma
Back Extra: Perineurioma
- Clinical: Perineuriomas of soft tissue usually present as painless masses, most commonly in the lower limbs, and are slightly more common in females than males.
- Micro: Soft tissue perineuriomas typically show a storiform or whorled growth pattern with slender spindle cells, characteristic delicate bipolar cytoplasmic processes, and a collagenous stroma.
- Ancillary: By immunohistochemistry, perineuriomas consistently express EMA and often CD34, but are negative for S100, SOX10, and GFAP.
Reference Gallery:
Perineurioma. Sclerosing perineurioma composed of cords of epithelioid cells in a dense collagenous stroma.
Perineurioma of soft tissue. The tumour shows a storiform growth pattern.
Perineurioma of soft tissue. The tumour cells contain uniform ovoid to elongated nuclei. Note the fibrillary stroma.
Perineurioma. Perivascular whorls are a typical feature. Note the collagenous stroma.
Perineurioma. The lesion shows a lamellar arrangement of elongated spindle cells with tapering nuclei in a somewhat myxoid stroma.
Perineurioma. Reticular perineurioma composed of anastomosing elongated spindle cells with a lacy architecture.
Soft tissue perineurioma. Immunohistochemical staining for EMA highlights the delicate bipolar cytoplasmic processes of the tumour cells.
Soft tissue perineurioma. Expression of CD34 is often more diffuse than that of EMA.

Q: Microscopically, Schwannoma typically features a biphasic appearance with loose, hypocellular Antoni B tissue and compact Antoni A areas containing palisading nuclei known as [...].
Schwannoma. Alternating compact Antoni A (periphery) and loose Antoni B (centre) areas. Nuclear palisades, known as Verocay bodies, are noted in the Antoni A area on the right.
Plexiform schwannoma. At higher magnification, typical features of schwannoma are seen, including Verocay bodies.
A: Verocay bodies
Back Extra: Schwannoma
- Clinical: Schwannomas are often asymptomatic and discovered incidentally on imaging. They can cause pain, especially in the context of schwannomatosis.
- Micro: Conventional schwannomas show biphasic areas with compact Antoni A tissue (nuclear palisades, Verocay bodies) and loose Antoni B tissue (cobweb-like network of tumour processes).
- Ancillary: Immunohistochemistry shows diffuse positivity for S100 and SOX10, with less frequent and variable expression of GFAP.
Reference Gallery:
Schwannoma. Cut surface showing an encapsulated tan-grey tumour with foci of haemorrhage, yellowish-white foci of xanthic change, and cystic degeneration.
Schwannoma. Alternating compact Antoni A (periphery) and loose Antoni B (centre) areas. Nuclear palisades, known as Verocay bodies, are noted in the Antoni A area on the right.
Schwannoma. The formation of Schwannian whorls can raise the differential with meningioma.
Ancient schwannoma. The presence of scattered bizarre or atypical nuclei is often considered a degenerative phenomenon, which does not impact the prognosis.
Ancient schwannoma. Despite the nuclear atypia, the Ki-67 proliferation index is low, with the majority of bizarre nuclei being negative.
Cellular schwannoma. The marked hypercellularity and compact arrangement may be alarming, warranting consideration of a sarcoma in the differential diagnosis.
Cellular schwannoma. Mitotic figures are common, but the mitotic count is < 5 mitoses/mm2 in most examples.
Cellular schwannoma. Diffuse S100 positivity is typical and helps distinguish this schwannoma subtype from malignant peripheral nerve sheath tumour.
Cellular schwannoma. Retained H3K27me3 expression differs from the complete loss of staining in tumour nuclei of most malignant peripheral nerve sheath tumours.
Plexiform schwannoma. The presence of tumour within multiple nerve fascicles defines this subtype and often raises the differential of plexiform neurofibroma at low magnification.
Plexiform schwannoma. At higher magnification, typical features of schwannoma are seen, including Verocay bodies.
Syndrome-associated schwannoma. On MRI, a longitudinally extensive and/or multicentric/discontinuous-appearing nerve sheath tumour such as this should raise suspicion of a tumour predisposition syndrome such as schwannomatosis or neurofibromatosis type 2.

Q: Immunohistochemistry in a Schwannoma characteristically shows diffuse and strong positivity for SOX10 and [...], which is particularly useful in distinguishing cellular variants from malignant peripheral nerve sheath tumors.
Cellular schwannoma. Diffuse S100 positivity is typical and helps distinguish this schwannoma subtype from malignant peripheral nerve sheath tumour.
A: S100
Back Extra: Schwannoma
- Clinical: Schwannomas are often asymptomatic and discovered incidentally on imaging. They can cause pain, especially in the context of schwannomatosis.
- Micro: Conventional schwannomas show biphasic areas with compact Antoni A tissue (nuclear palisades, Verocay bodies) and loose Antoni B tissue (cobweb-like network of tumour processes).
- Ancillary: Immunohistochemistry shows diffuse positivity for S100 and SOX10, with less frequent and variable expression of GFAP.
Reference Gallery:
Schwannoma. Cut surface showing an encapsulated tan-grey tumour with foci of haemorrhage, yellowish-white foci of xanthic change, and cystic degeneration.
Schwannoma. Alternating compact Antoni A (periphery) and loose Antoni B (centre) areas. Nuclear palisades, known as Verocay bodies, are noted in the Antoni A area on the right.
Schwannoma. The formation of Schwannian whorls can raise the differential with meningioma.
Ancient schwannoma. The presence of scattered bizarre or atypical nuclei is often considered a degenerative phenomenon, which does not impact the prognosis.
Ancient schwannoma. Despite the nuclear atypia, the Ki-67 proliferation index is low, with the majority of bizarre nuclei being negative.
Cellular schwannoma. The marked hypercellularity and compact arrangement may be alarming, warranting consideration of a sarcoma in the differential diagnosis.
Cellular schwannoma. Mitotic figures are common, but the mitotic count is < 5 mitoses/mm2 in most examples.
Cellular schwannoma. Diffuse S100 positivity is typical and helps distinguish this schwannoma subtype from malignant peripheral nerve sheath tumour.
Cellular schwannoma. Retained H3K27me3 expression differs from the complete loss of staining in tumour nuclei of most malignant peripheral nerve sheath tumours.
Plexiform schwannoma. The presence of tumour within multiple nerve fascicles defines this subtype and often raises the differential of plexiform neurofibroma at low magnification.
Plexiform schwannoma. At higher magnification, typical features of schwannoma are seen, including Verocay bodies.
Syndrome-associated schwannoma. On MRI, a longitudinally extensive and/or multicentric/discontinuous-appearing nerve sheath tumour such as this should raise suspicion of a tumour predisposition syndrome such as schwannomatosis or neurofibromatosis type 2.

Q: An ancient Schwannoma frequently exhibits scattered bizarre, atypical nuclei; however, these represent a benign [...] phenomenon rather than malignancy, as evidenced by a low Ki-67 index.
Ancient schwannoma. The presence of scattered bizarre or atypical nuclei is often considered a degenerative phenomenon, which does not impact the prognosis.
Ancient schwannoma. Despite the nuclear atypia, the Ki-67 proliferation index is low, with the majority of bizarre nuclei being negative.
A: degenerative
Back Extra: Schwannoma
- Clinical: Schwannomas are often asymptomatic and discovered incidentally on imaging. They can cause pain, especially in the context of schwannomatosis.
- Micro: Conventional schwannomas show biphasic areas with compact Antoni A tissue (nuclear palisades, Verocay bodies) and loose Antoni B tissue (cobweb-like network of tumour processes).
- Ancillary: Immunohistochemistry shows diffuse positivity for S100 and SOX10, with less frequent and variable expression of GFAP.
Reference Gallery:
Schwannoma. Cut surface showing an encapsulated tan-grey tumour with foci of haemorrhage, yellowish-white foci of xanthic change, and cystic degeneration.
Schwannoma. Alternating compact Antoni A (periphery) and loose Antoni B (centre) areas. Nuclear palisades, known as Verocay bodies, are noted in the Antoni A area on the right.
Schwannoma. The formation of Schwannian whorls can raise the differential with meningioma.
Ancient schwannoma. The presence of scattered bizarre or atypical nuclei is often considered a degenerative phenomenon, which does not impact the prognosis.
Ancient schwannoma. Despite the nuclear atypia, the Ki-67 proliferation index is low, with the majority of bizarre nuclei being negative.
Cellular schwannoma. The marked hypercellularity and compact arrangement may be alarming, warranting consideration of a sarcoma in the differential diagnosis.
Cellular schwannoma. Mitotic figures are common, but the mitotic count is < 5 mitoses/mm2 in most examples.
Cellular schwannoma. Diffuse S100 positivity is typical and helps distinguish this schwannoma subtype from malignant peripheral nerve sheath tumour.
Cellular schwannoma. Retained H3K27me3 expression differs from the complete loss of staining in tumour nuclei of most malignant peripheral nerve sheath tumours.
Plexiform schwannoma. The presence of tumour within multiple nerve fascicles defines this subtype and often raises the differential of plexiform neurofibroma at low magnification.
Plexiform schwannoma. At higher magnification, typical features of schwannoma are seen, including Verocay bodies.
Syndrome-associated schwannoma. On MRI, a longitudinally extensive and/or multicentric/discontinuous-appearing nerve sheath tumour such as this should raise suspicion of a tumour predisposition syndrome such as schwannomatosis or neurofibromatosis type 2.

Q: Microscopically, Solitary Circumscribed Neuroma is characterized by bland, spindle-shaped cells with wavy nuclei that frequently exhibit focal [...].
Solitary circumscribed neuroma. Higher magnification reveals banal spindle cells with focal palisading, set in a fibrous stroma.
A: palisading
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary circumscribed neuroma (SCN) typically presents as a slow-growing, firm, painless, circumscribed dermal-based nodule, most commonly found on the face.
- Micro: SCN is characterized by bland spindle-shaped cells with wavy nuclei, forming well-developed fascicles, and often showing focal palisading. A thin perineurial-derived fibrous capsule may be present.
- Ancillary: Immunohistochemistry shows diffuse positivity for S100 in Schwann cells and variable expression of NFP in small intratumoural axons.
Reference Gallery:
Solitary circumscribed neuroma. Higher magnification reveals banal spindle cells with focal palisading, set in a fibrous stroma.
Solitary circumscribed neuroma. Lesional Schwann cells stain diffusely positively with S100.
Solitary circumscribed neuroma. NFP is expressed by variable numbers of small intratumoural axons.
Solitary circumscribed neuroma. EMA staining highlights perineurial cells in the capsule.

Q: In Solitary Circumscribed Neuroma, immunohistochemistry reveals diffuse S100 positivity in Schwann cells and variable expression of [...] highlighting small intratumoral axons.
Solitary circumscribed neuroma. Lesional Schwann cells stain diffusely positively with S100.
Solitary circumscribed neuroma. NFP is expressed by variable numbers of small intratumoural axons.
A: neurofilament protein (NFP)
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary circumscribed neuroma (SCN) typically presents as a slow-growing, firm, painless, circumscribed dermal-based nodule, most commonly found on the face.
- Micro: SCN is characterized by bland spindle-shaped cells with wavy nuclei, forming well-developed fascicles, and often showing focal palisading. A thin perineurial-derived fibrous capsule may be present.
- Ancillary: Immunohistochemistry shows diffuse positivity for S100 in Schwann cells and variable expression of NFP in small intratumoural axons.
Reference Gallery:
Solitary circumscribed neuroma. Higher magnification reveals banal spindle cells with focal palisading, set in a fibrous stroma.
Solitary circumscribed neuroma. Lesional Schwann cells stain diffusely positively with S100.
Solitary circumscribed neuroma. NFP is expressed by variable numbers of small intratumoural axons.
Solitary circumscribed neuroma. EMA staining highlights perineurial cells in the capsule.

Q: The thin, perineurial-derived fibrous capsule of a Solitary Circumscribed Neuroma is characteristically highlighted by immunohistochemistry for [...].
Solitary circumscribed neuroma. EMA staining highlights perineurial cells in the capsule.
A: epithelial membrane antigen (EMA)
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary circumscribed neuroma (SCN) typically presents as a slow-growing, firm, painless, circumscribed dermal-based nodule, most commonly found on the face.
- Micro: SCN is characterized by bland spindle-shaped cells with wavy nuclei, forming well-developed fascicles, and often showing focal palisading. A thin perineurial-derived fibrous capsule may be present.
- Ancillary: Immunohistochemistry shows diffuse positivity for S100 in Schwann cells and variable expression of NFP in small intratumoural axons.
Reference Gallery:
Solitary circumscribed neuroma. Higher magnification reveals banal spindle cells with focal palisading, set in a fibrous stroma.
Solitary circumscribed neuroma. Lesional Schwann cells stain diffusely positively with S100.
Solitary circumscribed neuroma. NFP is expressed by variable numbers of small intratumoural axons.
Solitary circumscribed neuroma. EMA staining highlights perineurial cells in the capsule.

Q: In malignant melanotic nerve sheath tumors, immunohistochemistry typically demonstrates the complete loss of [...], a finding associated with Carney complex.
Malignant melanotic nerve sheath tumour. Although this patient was not known to have Carney complex, there was complete loss of PRKAR1A expression.
Malignant melanotic nerve sheath tumour. SNP array (OncoScan) analysis demonstrating copy-neutral loss of heterozygosity of the long arm of chromosome 17; PRKAR1A is localized to 17q24.2.
A: PRKAR1A
Back Extra: Malignant Melanotic Nerve Sheath Tumour
- Clinical: Presenting symptoms include pain, sensory abnormalities, and mass effect. Bone erosion may be seen in spinal nerve root tumours. MMNST occurs chiefly in adults, with an average age of 33.2 years, and is associated with Carney complex in some cases.
- Micro: The neoplastic cells grow in short fascicles or sheets, often showing a syncytial appearance. Heavy pigmentation, psammoma bodies, and the presence of melanocytic markers are characteristic.
- Ancillary: PRKAR1A expression is typically lost, and SNP arrays show hypodiploidy with monosomies of chromosomes 1, 2, and 17. Gene expression analyses show MMNSTs to clearly segregate from conventional schwannomas and melanomas.
Reference Gallery:
Malignant melanotic nerve sheath tumour. Malignant melanotic nerve sheath tumour presenting as an encapsulated posterior mediastinal mass in a 31-year-old woman.
Malignant melanotic nerve sheath tumour. Higher-power view showing heavily pigmented, vaguely syncytial epithelioid cells with visible nucleoli.
Malignant melanotic nerve sheath tumour. Although this patient was not known to have Carney complex, there was complete loss of PRKAR1A expression.
Malignant melanotic nerve sheath tumour. Malignant melanotic nerve sheath tumour presenting as a perigastric mass in a 45-year-old woman. Portions of this tumour showed pigmented spindle cell morphology.
Malignant melanotic nerve sheath tumour. Other areas in this tumour had a trabecular, epithelioid appearance, with scattered psammoma bodies.
Malignant melanotic nerve sheath tumour. Cervical lymph node metastasis in a 46-year-old man with malignant melanotic nerve sheath tumour. Neither the primary tumour nor the metastasis showed features that might have suggested an increased risk of metastasis.
Malignant melanotic nerve sheath tumour. SNP array (OncoScan) analysis demonstrating copy-neutral loss of heterozygosity of the long arm of chromosome 17; PRKAR1A is localized to 17q24.2.
Melanotic schwannoma. Malignant tumour arising in a thoracic nerve root. The sectioned tumour had the appearance and texture of dried tar, and it was circumscribed except for a portion (left) that invaded nearby soft tissues and vertebral bone.

Q: Histologically, malignant melanotic nerve sheath tumors frequently exhibit heavily pigmented, vague syncytial epithelioid cells alongside scattered [...].
Malignant melanotic nerve sheath tumour. Higher-power view showing heavily pigmented, vaguely syncytial epithelioid cells with visible nucleoli.
Malignant melanotic nerve sheath tumour. Other areas in this tumour had a trabecular, epithelioid appearance, with scattered psammoma bodies.
A: psammoma bodies
Back Extra: Malignant Melanotic Nerve Sheath Tumour
- Clinical: Presenting symptoms include pain, sensory abnormalities, and mass effect. Bone erosion may be seen in spinal nerve root tumours. MMNST occurs chiefly in adults, with an average age of 33.2 years, and is associated with Carney complex in some cases.
- Micro: The neoplastic cells grow in short fascicles or sheets, often showing a syncytial appearance. Heavy pigmentation, psammoma bodies, and the presence of melanocytic markers are characteristic.
- Ancillary: PRKAR1A expression is typically lost, and SNP arrays show hypodiploidy with monosomies of chromosomes 1, 2, and 17. Gene expression analyses show MMNSTs to clearly segregate from conventional schwannomas and melanomas.
Reference Gallery:
Malignant melanotic nerve sheath tumour. Malignant melanotic nerve sheath tumour presenting as an encapsulated posterior mediastinal mass in a 31-year-old woman.
Malignant melanotic nerve sheath tumour. Higher-power view showing heavily pigmented, vaguely syncytial epithelioid cells with visible nucleoli.
Malignant melanotic nerve sheath tumour. Although this patient was not known to have Carney complex, there was complete loss of PRKAR1A expression.
Malignant melanotic nerve sheath tumour. Malignant melanotic nerve sheath tumour presenting as a perigastric mass in a 45-year-old woman. Portions of this tumour showed pigmented spindle cell morphology.
Malignant melanotic nerve sheath tumour. Other areas in this tumour had a trabecular, epithelioid appearance, with scattered psammoma bodies.
Malignant melanotic nerve sheath tumour. Cervical lymph node metastasis in a 46-year-old man with malignant melanotic nerve sheath tumour. Neither the primary tumour nor the metastasis showed features that might have suggested an increased risk of metastasis.
Malignant melanotic nerve sheath tumour. SNP array (OncoScan) analysis demonstrating copy-neutral loss of heterozygosity of the long arm of chromosome 17; PRKAR1A is localized to 17q24.2.
Melanotic schwannoma. Malignant tumour arising in a thoracic nerve root. The sectioned tumour had the appearance and texture of dried tar, and it was circumscribed except for a portion (left) that invaded nearby soft tissues and vertebral bone.

Q: Grossly, a malignant melanotic nerve sheath tumor often arises from a spinal nerve root and displays the characteristic dark, heavily pigmented appearance and texture of [...].
Melanotic schwannoma. Malignant tumour arising in a thoracic nerve root. The sectioned tumour had the appearance and texture of dried tar, and it was circumscribed except for a portion (left) that invaded nearby soft tissues and vertebral bone.
A: dried tar
Back Extra: Malignant Melanotic Nerve Sheath Tumour
- Clinical: Presenting symptoms include pain, sensory abnormalities, and mass effect. Bone erosion may be seen in spinal nerve root tumours. MMNST occurs chiefly in adults, with an average age of 33.2 years, and is associated with Carney complex in some cases.
- Micro: The neoplastic cells grow in short fascicles or sheets, often showing a syncytial appearance. Heavy pigmentation, psammoma bodies, and the presence of melanocytic markers are characteristic.
- Ancillary: PRKAR1A expression is typically lost, and SNP arrays show hypodiploidy with monosomies of chromosomes 1, 2, and 17. Gene expression analyses show MMNSTs to clearly segregate from conventional schwannomas and melanomas.
Reference Gallery:
Malignant melanotic nerve sheath tumour. Malignant melanotic nerve sheath tumour presenting as an encapsulated posterior mediastinal mass in a 31-year-old woman.
Malignant melanotic nerve sheath tumour. Higher-power view showing heavily pigmented, vaguely syncytial epithelioid cells with visible nucleoli.
Malignant melanotic nerve sheath tumour. Although this patient was not known to have Carney complex, there was complete loss of PRKAR1A expression.
Malignant melanotic nerve sheath tumour. Malignant melanotic nerve sheath tumour presenting as a perigastric mass in a 45-year-old woman. Portions of this tumour showed pigmented spindle cell morphology.
Malignant melanotic nerve sheath tumour. Other areas in this tumour had a trabecular, epithelioid appearance, with scattered psammoma bodies.
Malignant melanotic nerve sheath tumour. Cervical lymph node metastasis in a 46-year-old man with malignant melanotic nerve sheath tumour. Neither the primary tumour nor the metastasis showed features that might have suggested an increased risk of metastasis.
Malignant melanotic nerve sheath tumour. SNP array (OncoScan) analysis demonstrating copy-neutral loss of heterozygosity of the long arm of chromosome 17; PRKAR1A is localized to 17q24.2.
Melanotic schwannoma. Malignant tumour arising in a thoracic nerve root. The sectioned tumour had the appearance and texture of dried tar, and it was circumscribed except for a portion (left) that invaded nearby soft tissues and vertebral bone.

Q: High-grade Malignant Peripheral Nerve Sheath Tumor typically shows a spindle cell morphology with alternating hypercellular and hypocellular areas, and immunohistochemistry often demonstrates a characteristic loss of [...].
Malignant peripheral nerve sheath tumour. The tumour is composed of alternating cellular and less cellular areas (marble-like pattern).
Malignant peripheral nerve sheath tumour. High-power view demonstrating the spindle-shaped and wavy nuclei characteristic of malignant peripheral nerve sheath tumour.
Malignant peripheral nerve sheath tumour. Malignant peripheral nerve sheath tumour demonstrating loss of H3K27me3.
A: H3K27me3
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumour (MPNST) is commonly seen in adults aged 20-50 years, often presenting as a painful or painless mass. Patients with neurofibromatosis type 1 (NF1) are at higher risk and often diagnosed at a younger age.
- Micro: MPNSTs exhibit a characteristic spindle cell morphology with alternating hypercellular and hypocellular areas, often with wavy nuclei and geographical necrosis. Heterologous differentiation is seen in about 15% of cases, including skeletal muscle, bone, and glandular elements.
- Ancillary: Immunohistochemically, MPNSTs may show patchy staining for S100 and SOX10. Loss of H3K27me3 is a helpful marker, particularly in high-grade tumours. Epithelioid MPNSTs show strong and diffuse staining for S100 and SOX10, and loss of SMARCB1.
Reference Gallery:
Malignant peripheral nerve sheath tumour arising in plexiform neurofibroma. Malignant peripheral nerve sheath tumour arising in a nerve involved by a plexiform neurofibroma (proximal and distal to tumour) in a patient with neurofibromatosis type 1. The tumour has variegated tan, red, and yellow areas.
Malignant peripheral nerve sheath tumour. The tumour is composed of alternating cellular and less cellular areas (marble-like pattern).
Malignant peripheral nerve sheath tumour. High-power view demonstrating the spindle-shaped and wavy nuclei characteristic of malignant peripheral nerve sheath tumour.
Malignant peripheral nerve sheath tumour. High-grade malignant peripheral nerve sheath tumour arising in a patient with neurofibromatosis type 1. The sarcoma shows marked pleomorphism, mimicking an undifferentiated pleomorphic sarcoma.
Malignant triton tumour. Malignant peripheral nerve sheath tumour with extensive rhabdomyoblastic differentiation (malignant triton tumour).
Malignant peripheral nerve sheath tumour with angiosarcoma. High-grade angiosarcomatous component in a malignant peripheral nerve sheath tumour arising in a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour with glands. Malignant peripheral nerve sheath tumour with glandular differentiation.
Malignant peripheral nerve sheath tumour. Malignant peripheral nerve sheath tumour demonstrating loss of H3K27me3.
Epithelioid malignant peripheral nerve sheath tumour. The neoplastic cells are epithelioid, with eosinophilic cytoplasm and nuclei with prominent nucleoli.
Epithelioid malignant peripheral nerve sheath tumour. Epithelioid malignant peripheral nerve sheath tumour showing loss of SMARCB1 (INI1) staining. Normal cells in the background show nuclear staining.

Q: A Malignant Peripheral Nerve Sheath Tumor that exhibits extensive heterologous rhabdomyoblastic differentiation is specifically referred to as a [...].
Malignant triton tumour. Malignant peripheral nerve sheath tumour with extensive rhabdomyoblastic differentiation (malignant triton tumour).
A: malignant triton tumor
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumour (MPNST) is commonly seen in adults aged 20-50 years, often presenting as a painful or painless mass. Patients with neurofibromatosis type 1 (NF1) are at higher risk and often diagnosed at a younger age.
- Micro: MPNSTs exhibit a characteristic spindle cell morphology with alternating hypercellular and hypocellular areas, often with wavy nuclei and geographical necrosis. Heterologous differentiation is seen in about 15% of cases, including skeletal muscle, bone, and glandular elements.
- Ancillary: Immunohistochemically, MPNSTs may show patchy staining for S100 and SOX10. Loss of H3K27me3 is a helpful marker, particularly in high-grade tumours. Epithelioid MPNSTs show strong and diffuse staining for S100 and SOX10, and loss of SMARCB1.
Reference Gallery:
Malignant peripheral nerve sheath tumour arising in plexiform neurofibroma. Malignant peripheral nerve sheath tumour arising in a nerve involved by a plexiform neurofibroma (proximal and distal to tumour) in a patient with neurofibromatosis type 1. The tumour has variegated tan, red, and yellow areas.
Malignant peripheral nerve sheath tumour. The tumour is composed of alternating cellular and less cellular areas (marble-like pattern).
Malignant peripheral nerve sheath tumour. High-power view demonstrating the spindle-shaped and wavy nuclei characteristic of malignant peripheral nerve sheath tumour.
Malignant peripheral nerve sheath tumour. High-grade malignant peripheral nerve sheath tumour arising in a patient with neurofibromatosis type 1. The sarcoma shows marked pleomorphism, mimicking an undifferentiated pleomorphic sarcoma.
Malignant triton tumour. Malignant peripheral nerve sheath tumour with extensive rhabdomyoblastic differentiation (malignant triton tumour).
Malignant peripheral nerve sheath tumour with angiosarcoma. High-grade angiosarcomatous component in a malignant peripheral nerve sheath tumour arising in a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour with glands. Malignant peripheral nerve sheath tumour with glandular differentiation.
Malignant peripheral nerve sheath tumour. Malignant peripheral nerve sheath tumour demonstrating loss of H3K27me3.
Epithelioid malignant peripheral nerve sheath tumour. The neoplastic cells are epithelioid, with eosinophilic cytoplasm and nuclei with prominent nucleoli.
Epithelioid malignant peripheral nerve sheath tumour. Epithelioid malignant peripheral nerve sheath tumour showing loss of SMARCB1 (INI1) staining. Normal cells in the background show nuclear staining.

Q: Unlike the conventional spindle-cell type, the epithelioid variant of Malignant Peripheral Nerve Sheath Tumor is characterized by strong S100 and SOX10 positivity along with the immunohistochemical loss of [...].
Epithelioid malignant peripheral nerve sheath tumour. The neoplastic cells are epithelioid, with eosinophilic cytoplasm and nuclei with prominent nucleoli.
Epithelioid malignant peripheral nerve sheath tumour. Epithelioid malignant peripheral nerve sheath tumour showing loss of SMARCB1 (INI1) staining. Normal cells in the background show nuclear staining.
A: SMARCB1
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumour (MPNST) is commonly seen in adults aged 20-50 years, often presenting as a painful or painless mass. Patients with neurofibromatosis type 1 (NF1) are at higher risk and often diagnosed at a younger age.
- Micro: MPNSTs exhibit a characteristic spindle cell morphology with alternating hypercellular and hypocellular areas, often with wavy nuclei and geographical necrosis. Heterologous differentiation is seen in about 15% of cases, including skeletal muscle, bone, and glandular elements.
- Ancillary: Immunohistochemically, MPNSTs may show patchy staining for S100 and SOX10. Loss of H3K27me3 is a helpful marker, particularly in high-grade tumours. Epithelioid MPNSTs show strong and diffuse staining for S100 and SOX10, and loss of SMARCB1.
Reference Gallery:
Malignant peripheral nerve sheath tumour arising in plexiform neurofibroma. Malignant peripheral nerve sheath tumour arising in a nerve involved by a plexiform neurofibroma (proximal and distal to tumour) in a patient with neurofibromatosis type 1. The tumour has variegated tan, red, and yellow areas.
Malignant peripheral nerve sheath tumour. The tumour is composed of alternating cellular and less cellular areas (marble-like pattern).
Malignant peripheral nerve sheath tumour. High-power view demonstrating the spindle-shaped and wavy nuclei characteristic of malignant peripheral nerve sheath tumour.
Malignant peripheral nerve sheath tumour. High-grade malignant peripheral nerve sheath tumour arising in a patient with neurofibromatosis type 1. The sarcoma shows marked pleomorphism, mimicking an undifferentiated pleomorphic sarcoma.
Malignant triton tumour. Malignant peripheral nerve sheath tumour with extensive rhabdomyoblastic differentiation (malignant triton tumour).
Malignant peripheral nerve sheath tumour with angiosarcoma. High-grade angiosarcomatous component in a malignant peripheral nerve sheath tumour arising in a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumour with glands. Malignant peripheral nerve sheath tumour with glandular differentiation.
Malignant peripheral nerve sheath tumour. Malignant peripheral nerve sheath tumour demonstrating loss of H3K27me3.
Epithelioid malignant peripheral nerve sheath tumour. The neoplastic cells are epithelioid, with eosinophilic cytoplasm and nuclei with prominent nucleoli.
Epithelioid malignant peripheral nerve sheath tumour. Epithelioid malignant peripheral nerve sheath tumour showing loss of SMARCB1 (INI1) staining. Normal cells in the background show nuclear staining.

Q: A well-circumscribed, frequently painful benign tumor characterized by thick muscle-coated blood vessels with intervascular smooth muscle bundles represents the venous type of [...].
Angioleiomyoma, venous type. Venous-type angioleiomyoma consists of thick muscle-coated blood vessels with intervascular smooth muscle bundles.
Angioleiomyoma. This lesion has an attached vein and shows sharp circumscription.
A: angioleiomyoma
Back Extra: Angioleiomyoma
- Clinical: Approximately half of angioleiomyomas are painful and are most common in the fourth through sixth decades of life, with a slightly higher incidence in females.
- Micro: The venous type of angioleiomyoma is characterized by thick muscle-coated blood vessels with intervascular smooth muscle bundles.
- Ancillary: Immunohistochemically, the tumour cells are diffusely positive for SMA and calponin, and usually strongly positive for h-caldesmon.
Reference Gallery:
Angioleiomyoma, venous type. Venous-type angioleiomyoma consists of thick muscle-coated blood vessels with intervascular smooth muscle bundles.
Angioleiomyoma, solid type. Solid-type angioleiomyoma is composed of a proliferation of smooth muscle cells with slit-like vascular channels.
Angioleiomyoma with adipocytic metaplasia. Legend text not found
Angioleiomyoma. This lesion has an attached vein and shows sharp circumscription.
Angioleiomyoma, cavernous type. This lesion is composed of cavernously dilated vascular channels with attenuated walls of smooth muscle cells.

Q: The solid variant of angioleiomyoma is histologically composed of a dense proliferation of smooth muscle cells featuring numerous [...] vascular channels.
Angioleiomyoma, solid type. Solid-type angioleiomyoma is composed of a proliferation of smooth muscle cells with slit-like vascular channels.
A: slit-like
Back Extra: Angioleiomyoma
- Clinical: Approximately half of angioleiomyomas are painful and are most common in the fourth through sixth decades of life, with a slightly higher incidence in females.
- Micro: The venous type of angioleiomyoma is characterized by thick muscle-coated blood vessels with intervascular smooth muscle bundles.
- Ancillary: Immunohistochemically, the tumour cells are diffusely positive for SMA and calponin, and usually strongly positive for h-caldesmon.
Reference Gallery:
Angioleiomyoma, venous type. Venous-type angioleiomyoma consists of thick muscle-coated blood vessels with intervascular smooth muscle bundles.
Angioleiomyoma, solid type. Solid-type angioleiomyoma is composed of a proliferation of smooth muscle cells with slit-like vascular channels.
Angioleiomyoma with adipocytic metaplasia. Legend text not found
Angioleiomyoma. This lesion has an attached vein and shows sharp circumscription.
Angioleiomyoma, cavernous type. This lesion is composed of cavernously dilated vascular channels with attenuated walls of smooth muscle cells.

Q: The cavernous subtype of angioleiomyoma is microscopically characterized by cavernously dilated vascular channels with [...] walls composed of smooth muscle cells.
Angioleiomyoma, cavernous type. This lesion is composed of cavernously dilated vascular channels with attenuated walls of smooth muscle cells.
A: attenuated
Back Extra: Angioleiomyoma
- Clinical: Approximately half of angioleiomyomas are painful and are most common in the fourth through sixth decades of life, with a slightly higher incidence in females.
- Micro: The venous type of angioleiomyoma is characterized by thick muscle-coated blood vessels with intervascular smooth muscle bundles.
- Ancillary: Immunohistochemically, the tumour cells are diffusely positive for SMA and calponin, and usually strongly positive for h-caldesmon.
Reference Gallery:
Angioleiomyoma, venous type. Venous-type angioleiomyoma consists of thick muscle-coated blood vessels with intervascular smooth muscle bundles.
Angioleiomyoma, solid type. Solid-type angioleiomyoma is composed of a proliferation of smooth muscle cells with slit-like vascular channels.
Angioleiomyoma with adipocytic metaplasia. Legend text not found
Angioleiomyoma. This lesion has an attached vein and shows sharp circumscription.
Angioleiomyoma, cavernous type. This lesion is composed of cavernously dilated vascular channels with attenuated walls of smooth muscle cells.

Q: A patient presents with a painful, reddish-blue nodule that is highly sensitive to cold and minor tactile stimulation. Biopsy reveals a circumscribed mass composed of solid sheets of small, uniform, round cells with sharply defined cell borders. This presentation is characteristic of a [...].
Glomus tumour. Glomus tumour, solid type, consisting of round, uniform cells with well-defined cell margins.
Glomus tumour. Small glomus tumour forming a circumscribed mass.
A: glomus tumor
Back Extra: Glomus Tumour
- Clinical: Cutaneous glomus tumours are typically small, reddish-blue nodules often associated with a long history of pain, particularly with exposure to cold or minor tactile stimulation.
- Micro: Glomus cells are small, uniform, and rounded, with a centrally placed round nucleus, amphophilic to lightly eosinophilic cytoplasm, and sharply defined cell borders.
- Ancillary: Glomus tumours typically express SMA and MSA and have abundant pericellular production of collagen IV. BRAF p.Val600Glu mutations are seen in the BRAF-mutated molecular subset.
Reference Gallery:
Glomus tumour. Glomus tumour, solid type, consisting of round, uniform cells with well-defined cell margins.
Glomus tumour. Glomangioma, composed of dilated vascular spaces lined by several layers of glomus cells.
Glomus tumour. The tumour cells are strongly positive for SMA.
Symplastic glomus tumour. Areas of prominent nuclear atypia but without mitotic activity.
Malignant glomus tumour. Spindle cell type.
Malignant glomus tumour. Round cell type, with mitotic activity.
Glomus tumour. Small glomus tumour forming a circumscribed mass.

Q: Immunohistochemically, the uniform, round neoplastic cells of a glomus tumor characteristically show strong, diffuse positivity for [...] (smooth muscle actin) and exhibit abundant pericellular collagen IV production.
Glomus tumour. The tumour cells are strongly positive for SMA.
A: SMA
Back Extra: Glomus Tumour
- Clinical: Cutaneous glomus tumours are typically small, reddish-blue nodules often associated with a long history of pain, particularly with exposure to cold or minor tactile stimulation.
- Micro: Glomus cells are small, uniform, and rounded, with a centrally placed round nucleus, amphophilic to lightly eosinophilic cytoplasm, and sharply defined cell borders.
- Ancillary: Glomus tumours typically express SMA and MSA and have abundant pericellular production of collagen IV. BRAF p.Val600Glu mutations are seen in the BRAF-mutated molecular subset.
Reference Gallery:
Glomus tumour. Glomus tumour, solid type, consisting of round, uniform cells with well-defined cell margins.
Glomus tumour. Glomangioma, composed of dilated vascular spaces lined by several layers of glomus cells.
Glomus tumour. The tumour cells are strongly positive for SMA.
Symplastic glomus tumour. Areas of prominent nuclear atypia but without mitotic activity.
Malignant glomus tumour. Spindle cell type.
Malignant glomus tumour. Round cell type, with mitotic activity.
Glomus tumour. Small glomus tumour forming a circumscribed mass.

Q: A morphological variant of a glomus tumor characterized by prominent, dilated vascular spaces lined by several layers of round, uniform neoplastic cells is known as a [...].
Glomus tumour. Glomangioma, composed of dilated vascular spaces lined by several layers of glomus cells.
A: glomangioma
Back Extra: Glomus Tumour
- Clinical: Cutaneous glomus tumours are typically small, reddish-blue nodules often associated with a long history of pain, particularly with exposure to cold or minor tactile stimulation.
- Micro: Glomus cells are small, uniform, and rounded, with a centrally placed round nucleus, amphophilic to lightly eosinophilic cytoplasm, and sharply defined cell borders.
- Ancillary: Glomus tumours typically express SMA and MSA and have abundant pericellular production of collagen IV. BRAF p.Val600Glu mutations are seen in the BRAF-mutated molecular subset.
Reference Gallery:
Glomus tumour. Glomus tumour, solid type, consisting of round, uniform cells with well-defined cell margins.
Glomus tumour. Glomangioma, composed of dilated vascular spaces lined by several layers of glomus cells.
Glomus tumour. The tumour cells are strongly positive for SMA.
Symplastic glomus tumour. Areas of prominent nuclear atypia but without mitotic activity.
Malignant glomus tumour. Spindle cell type.
Malignant glomus tumour. Round cell type, with mitotic activity.
Glomus tumour. Small glomus tumour forming a circumscribed mass.

Q: Microscopically, Myopericytoma is classically characterized by a [...] growth of plump, spindled myoid tumor cells around small vessels.
Myopericytoma. A concentric, perivascular growth of plump spindled, myoid tumour cells is characteristic.
Myopericytoma. The so-called classic, solid type of myopericytoma with thick-walled vessels surrounded concentrically by plump spindled tumour cells.
A: concentric, perivascular
Back Extra: Myopericytoma
- Clinical: Myopericytoma usually presents as a painless, slow-growing, superficially located nodule, often involving the distal extremities.
- Micro: Characterized by a concentric, perivascular growth of plump spindled, myoid tumour cells around numerous small vessels.
- Ancillary: Germline mutations in the PDGFRB gene are associated with familial, autosomal dominant infantile myofibromatosis.
Reference Gallery:
Myopericytoma. A concentric, perivascular growth of plump spindled, myoid tumour cells is characteristic.
Myopericytoma. The so-called classic, solid type of myopericytoma with thick-walled vessels surrounded concentrically by plump spindled tumour cells.
Myopericytoma. Numerous thin-walled branching vessels and a perivascular growth of myoid tumour cells are seen in the haemangiopericytoma type of myopericytoma.
Myopericytoma. An example of intravascular myopericytoma.
Myopericytoma. High-power view of an intravascular myopericytoma showing a perivascular growth of myoid tumour cells.
Malignant myopericytoma. An infiltrating neoplasm with a perivascular growth of neoplastic cells is seen.
Malignant myopericytoma. A perivascular growth of atypical myoid tumour cells and numerous mitoses, including atypical mitotic figures, is present.
Myopericytomatosis. Numerous small nodular aggregates with features of myopericytoma are seen.
Myopericytomatosis. An intramural growth is noted.
Cellular myofibroma. Cellular myofibromas of the type showing SRF-RELA fusions may consist largely of intersecting fascicles of spindled cells, simulating a spindle cell sarcoma.
Cellular myofibroma. Identification of more-typical areas of myofibroma, showing hyalinized nodules, is key to their distinction from various spindle cell sarcomas. Molecular genetic studies for SRF-RELA may also be helpful.

Q: In addition to the classic solid type, Myopericytoma can demonstrate a [...]-like pattern characterized by numerous thin-walled branching vessels surrounded by myoid tumor cells.
Myopericytoma. Numerous thin-walled branching vessels and a perivascular growth of myoid tumour cells are seen in the haemangiopericytoma type of myopericytoma.
A: hemangiopericytoma
Back Extra: Myopericytoma
- Clinical: Myopericytoma usually presents as a painless, slow-growing, superficially located nodule, often involving the distal extremities.
- Micro: Characterized by a concentric, perivascular growth of plump spindled, myoid tumour cells around numerous small vessels.
- Ancillary: Germline mutations in the PDGFRB gene are associated with familial, autosomal dominant infantile myofibromatosis.
Reference Gallery:
Myopericytoma. A concentric, perivascular growth of plump spindled, myoid tumour cells is characteristic.
Myopericytoma. The so-called classic, solid type of myopericytoma with thick-walled vessels surrounded concentrically by plump spindled tumour cells.
Myopericytoma. Numerous thin-walled branching vessels and a perivascular growth of myoid tumour cells are seen in the haemangiopericytoma type of myopericytoma.
Myopericytoma. An example of intravascular myopericytoma.
Myopericytoma. High-power view of an intravascular myopericytoma showing a perivascular growth of myoid tumour cells.
Malignant myopericytoma. An infiltrating neoplasm with a perivascular growth of neoplastic cells is seen.
Malignant myopericytoma. A perivascular growth of atypical myoid tumour cells and numerous mitoses, including atypical mitotic figures, is present.
Myopericytomatosis. Numerous small nodular aggregates with features of myopericytoma are seen.
Myopericytomatosis. An intramural growth is noted.
Cellular myofibroma. Cellular myofibromas of the type showing SRF-RELA fusions may consist largely of intersecting fascicles of spindled cells, simulating a spindle cell sarcoma.
Cellular myofibroma. Identification of more-typical areas of myofibroma, showing hyalinized nodules, is key to their distinction from various spindle cell sarcomas. Molecular genetic studies for SRF-RELA may also be helpful.

Q: A well-recognized morphologic variant of Myopericytoma occurs entirely within the lumen of a blood vessel, known as an [...] myopericytoma.
Myopericytoma. An example of intravascular myopericytoma.
Myopericytoma. High-power view of an intravascular myopericytoma showing a perivascular growth of myoid tumour cells.
A: intravascular
Back Extra: Myopericytoma
- Clinical: Myopericytoma usually presents as a painless, slow-growing, superficially located nodule, often involving the distal extremities.
- Micro: Characterized by a concentric, perivascular growth of plump spindled, myoid tumour cells around numerous small vessels.
- Ancillary: Germline mutations in the PDGFRB gene are associated with familial, autosomal dominant infantile myofibromatosis.
Reference Gallery:
Myopericytoma. A concentric, perivascular growth of plump spindled, myoid tumour cells is characteristic.
Myopericytoma. The so-called classic, solid type of myopericytoma with thick-walled vessels surrounded concentrically by plump spindled tumour cells.
Myopericytoma. Numerous thin-walled branching vessels and a perivascular growth of myoid tumour cells are seen in the haemangiopericytoma type of myopericytoma.
Myopericytoma. An example of intravascular myopericytoma.
Myopericytoma. High-power view of an intravascular myopericytoma showing a perivascular growth of myoid tumour cells.
Malignant myopericytoma. An infiltrating neoplasm with a perivascular growth of neoplastic cells is seen.
Malignant myopericytoma. A perivascular growth of atypical myoid tumour cells and numerous mitoses, including atypical mitotic figures, is present.
Myopericytomatosis. Numerous small nodular aggregates with features of myopericytoma are seen.
Myopericytomatosis. An intramural growth is noted.
Cellular myofibroma. Cellular myofibromas of the type showing SRF-RELA fusions may consist largely of intersecting fascicles of spindled cells, simulating a spindle cell sarcoma.
Cellular myofibroma. Identification of more-typical areas of myofibroma, showing hyalinized nodules, is key to their distinction from various spindle cell sarcomas. Molecular genetic studies for SRF-RELA may also be helpful.

Q: Microscopically, large polygonal cells with abundant granular eosinophilic cytoplasm and scattered spider cells (characterized by cytoplasmic clearing) are classic for the adult subtype of [...].
Adult rhabdomyoma. Adult rhabdomyoma showing mature rhabdomyoblasts with abundant eosinophilic cytoplasm. Scattered spider cells with cytoplasmic clearing are present.
A: Rhabdomyoma
Back Extra: Rhabdomyoma
- Clinical: Rhabdomyomas usually present as slow-growing, painless masses, but some grow rapidly. Other symptoms include hoarseness, obstructive sleep apnoea, and dysphagia.
- Micro: Classic fetal rhabdomyomas contain irregular bundles of immature skeletal muscle fibres within a myxoid background. Adult rhabdomyomas consist of large polygonal cells with abundant granular eosinophilic cytoplasm.
- Ancillary: Immunohistochemical stains used for ancillary diagnosis include desmin, MSA, MYOD1, and myogenin. Desmin expression is generally strong and diffuse.
Reference Gallery:
Adult rhabdomyoma. Adult rhabdomyoma showing mature rhabdomyoblasts with abundant eosinophilic cytoplasm. Scattered spider cells with cytoplasmic clearing are present.
Fetal rhabdomyoma. Fetal rhabdomyoma containing alternating bands of myotubes and loose myxoid stroma.
Adult rhabdomyoma. Adult rhabdomyoma with strong, diffuse desmin expression.
Adult rhabdomyoma. Adult rhabdomyomas typically show variable degrees of myogenin expression.
Fetal rhabdomyoma. Intermediate juvenile rhabdomyoma with increased cellularity and a mixture of mature rhabdomyoblasts and cells with smooth muscle features, lacking a myxoid component.
Vaginal rhabdomyoma. Whole mount shows a polypoid configuration and fibrous stroma.

Q: The classic fetal subtype of [...] is characterized microscopically by alternating bands of immature skeletal muscle fibers (myotubes) within a loose myxoid background.
Fetal rhabdomyoma. Fetal rhabdomyoma containing alternating bands of myotubes and loose myxoid stroma.
A: Rhabdomyoma
Back Extra: Rhabdomyoma
- Clinical: Rhabdomyomas usually present as slow-growing, painless masses, but some grow rapidly. Other symptoms include hoarseness, obstructive sleep apnoea, and dysphagia.
- Micro: Classic fetal rhabdomyomas contain irregular bundles of immature skeletal muscle fibres within a myxoid background. Adult rhabdomyomas consist of large polygonal cells with abundant granular eosinophilic cytoplasm.
- Ancillary: Immunohistochemical stains used for ancillary diagnosis include desmin, MSA, MYOD1, and myogenin. Desmin expression is generally strong and diffuse.
Reference Gallery:
Adult rhabdomyoma. Adult rhabdomyoma showing mature rhabdomyoblasts with abundant eosinophilic cytoplasm. Scattered spider cells with cytoplasmic clearing are present.
Fetal rhabdomyoma. Fetal rhabdomyoma containing alternating bands of myotubes and loose myxoid stroma.
Adult rhabdomyoma. Adult rhabdomyoma with strong, diffuse desmin expression.
Adult rhabdomyoma. Adult rhabdomyomas typically show variable degrees of myogenin expression.
Fetal rhabdomyoma. Intermediate juvenile rhabdomyoma with increased cellularity and a mixture of mature rhabdomyoblasts and cells with smooth muscle features, lacking a myxoid component.
Vaginal rhabdomyoma. Whole mount shows a polypoid configuration and fibrous stroma.

Q: In the diagnostic workup of Rhabdomyoma, immunohistochemistry generally exhibits strong and diffuse expression of the intermediate filament [...], along with variable positivity for skeletal muscle markers like MYOD1 and myogenin.
Adult rhabdomyoma. Adult rhabdomyoma with strong, diffuse desmin expression.
Adult rhabdomyoma. Adult rhabdomyomas typically show variable degrees of myogenin expression.
A: desmin
Back Extra: Rhabdomyoma
- Clinical: Rhabdomyomas usually present as slow-growing, painless masses, but some grow rapidly. Other symptoms include hoarseness, obstructive sleep apnoea, and dysphagia.
- Micro: Classic fetal rhabdomyomas contain irregular bundles of immature skeletal muscle fibres within a myxoid background. Adult rhabdomyomas consist of large polygonal cells with abundant granular eosinophilic cytoplasm.
- Ancillary: Immunohistochemical stains used for ancillary diagnosis include desmin, MSA, MYOD1, and myogenin. Desmin expression is generally strong and diffuse.
Reference Gallery:
Adult rhabdomyoma. Adult rhabdomyoma showing mature rhabdomyoblasts with abundant eosinophilic cytoplasm. Scattered spider cells with cytoplasmic clearing are present.
Fetal rhabdomyoma. Fetal rhabdomyoma containing alternating bands of myotubes and loose myxoid stroma.
Adult rhabdomyoma. Adult rhabdomyoma with strong, diffuse desmin expression.
Adult rhabdomyoma. Adult rhabdomyomas typically show variable degrees of myogenin expression.
Fetal rhabdomyoma. Intermediate juvenile rhabdomyoma with increased cellularity and a mixture of mature rhabdomyoblasts and cells with smooth muscle features, lacking a myxoid component.
Vaginal rhabdomyoma. Whole mount shows a polypoid configuration and fibrous stroma.

Q: Microscopically, Alveolar Rhabdomyosarcoma is characterized by a monomorphic population of primitive round cells arranged in nests separated by [...], often with a single layer of tumor cells adhering to these structures.
Alveolar rhabdomyosarcoma. A proliferation of tumour cells with the characteristic alveolar growth pattern.
Alveolar rhabdomyosarcoma. A single layer of tumour cells adheres to fibrovascular septa.
A: fibrovascular septa
Back Extra: Alveolar Rhabdomyosarcoma
- Clinical: Alveolar rhabdomyosarcoma is a highly aggressive tumour that often presents with distant metastases at diagnosis, particularly in the head and neck region, leading to cranial nerve deficits or spinal nerve compression.
- Micro: Alveolar rhabdomyosarcoma is characterized by a monomorphic population of primitive round cells arranged in nests separated by fibrovascular septa, often with multinucleated giant cells.
- Ancillary: Strong and diffuse immunohistochemical expression of myogenin, along with the presence of PAX3-FOXO1 or PAX7-FOXO1 fusion genes, are key diagnostic features of alveolar rhabdomyosarcoma.
Reference Gallery:
Alveolar rhabdomyosarcoma. CT of a maxillary sinus alveolar rhabdomyosarcoma (arrows).
Alveolar rhabdomyosarcoma. A proliferation of tumour cells with the characteristic alveolar growth pattern.
Alveolar rhabdomyosarcoma. A single layer of tumour cells adheres to fibrovascular septa.
Alveolar rhabdomyosarcoma. Solid subtype shows a proliferation of small round tumour cells arranged in a sheet-like pattern without fibrovascular septa.
Alveolar rhabdomyosarcoma. Multinucleated giant cells with multiple and peripherally placed nuclei.
Alveolar rhabdomyosarcoma. Diffuse and strong immunoexpression of myogenin.
Alveolar rhabdomyosarcoma. Cytologically, tumour cells form dyscohesive clusters, with comparatively monomorphous round nuclei and scant cytoplasm.
Alveolar rhabdomyosarcoma. Detection of PAX3-FOXO1 fusion gene by RT-PCR and direct sequencing.
Alveolar rhabdomyosarcoma. Interphase FISH analysis showing amplification of the PAX7-FOXO1 fusion gene (juxtaposed red and green signals) by 1;13 translocation breakpoint-flanking probes.
Wildtype and fusion products associated with 2;13 and 1;13 translocations. The paired box (PB), octapeptide, homeobox domain (HD), and forkhead domain (FD) are shown as grey boxes. Transcriptional domains (DNA-binding domain [DBD] and transcriptional activation domain [TAD]) are indicated as solid horizontal bars. The translocation fusion point is shown as a vertical dashed line.
Rhabdomyosarcoma with embryonal and alveolar components. Foci of small round tumour cells and differentiating rhabdomyoblasts. Most of these tumours lack the presence of a FOXO1-related fusion and probably represent embryonal rhabdomyosarcoma.

Q: A key ancillary diagnostic feature of Alveolar Rhabdomyosarcoma is the strong and diffuse immunohistochemical expression of [...].
Alveolar rhabdomyosarcoma. Diffuse and strong immunoexpression of myogenin.
A: myogenin
Back Extra: Alveolar Rhabdomyosarcoma
- Clinical: Alveolar rhabdomyosarcoma is a highly aggressive tumour that often presents with distant metastases at diagnosis, particularly in the head and neck region, leading to cranial nerve deficits or spinal nerve compression.
- Micro: Alveolar rhabdomyosarcoma is characterized by a monomorphic population of primitive round cells arranged in nests separated by fibrovascular septa, often with multinucleated giant cells.
- Ancillary: Strong and diffuse immunohistochemical expression of myogenin, along with the presence of PAX3-FOXO1 or PAX7-FOXO1 fusion genes, are key diagnostic features of alveolar rhabdomyosarcoma.
Reference Gallery:
Alveolar rhabdomyosarcoma. CT of a maxillary sinus alveolar rhabdomyosarcoma (arrows).
Alveolar rhabdomyosarcoma. A proliferation of tumour cells with the characteristic alveolar growth pattern.
Alveolar rhabdomyosarcoma. A single layer of tumour cells adheres to fibrovascular septa.
Alveolar rhabdomyosarcoma. Solid subtype shows a proliferation of small round tumour cells arranged in a sheet-like pattern without fibrovascular septa.
Alveolar rhabdomyosarcoma. Multinucleated giant cells with multiple and peripherally placed nuclei.
Alveolar rhabdomyosarcoma. Diffuse and strong immunoexpression of myogenin.
Alveolar rhabdomyosarcoma. Cytologically, tumour cells form dyscohesive clusters, with comparatively monomorphous round nuclei and scant cytoplasm.
Alveolar rhabdomyosarcoma. Detection of PAX3-FOXO1 fusion gene by RT-PCR and direct sequencing.
Alveolar rhabdomyosarcoma. Interphase FISH analysis showing amplification of the PAX7-FOXO1 fusion gene (juxtaposed red and green signals) by 1;13 translocation breakpoint-flanking probes.
Wildtype and fusion products associated with 2;13 and 1;13 translocations. The paired box (PB), octapeptide, homeobox domain (HD), and forkhead domain (FD) are shown as grey boxes. Transcriptional domains (DNA-binding domain [DBD] and transcriptional activation domain [TAD]) are indicated as solid horizontal bars. The translocation fusion point is shown as a vertical dashed line.
Rhabdomyosarcoma with embryonal and alveolar components. Foci of small round tumour cells and differentiating rhabdomyoblasts. Most of these tumours lack the presence of a FOXO1-related fusion and probably represent embryonal rhabdomyosarcoma.

Q: The definitive molecular diagnostic feature of Alveolar Rhabdomyosarcoma is the presence of a PAX7-FOXO1 or [...] fusion gene.
Alveolar rhabdomyosarcoma. Detection of PAX3-FOXO1 fusion gene by RT-PCR and direct sequencing.
Alveolar rhabdomyosarcoma. Interphase FISH analysis showing amplification of the PAX7-FOXO1 fusion gene (juxtaposed red and green signals) by 1;13 translocation breakpoint-flanking probes.
A: PAX3-FOXO1
Back Extra: Alveolar Rhabdomyosarcoma
- Clinical: Alveolar rhabdomyosarcoma is a highly aggressive tumour that often presents with distant metastases at diagnosis, particularly in the head and neck region, leading to cranial nerve deficits or spinal nerve compression.
- Micro: Alveolar rhabdomyosarcoma is characterized by a monomorphic population of primitive round cells arranged in nests separated by fibrovascular septa, often with multinucleated giant cells.
- Ancillary: Strong and diffuse immunohistochemical expression of myogenin, along with the presence of PAX3-FOXO1 or PAX7-FOXO1 fusion genes, are key diagnostic features of alveolar rhabdomyosarcoma.
Reference Gallery:
Alveolar rhabdomyosarcoma. CT of a maxillary sinus alveolar rhabdomyosarcoma (arrows).
Alveolar rhabdomyosarcoma. A proliferation of tumour cells with the characteristic alveolar growth pattern.
Alveolar rhabdomyosarcoma. A single layer of tumour cells adheres to fibrovascular septa.
Alveolar rhabdomyosarcoma. Solid subtype shows a proliferation of small round tumour cells arranged in a sheet-like pattern without fibrovascular septa.
Alveolar rhabdomyosarcoma. Multinucleated giant cells with multiple and peripherally placed nuclei.
Alveolar rhabdomyosarcoma. Diffuse and strong immunoexpression of myogenin.
Alveolar rhabdomyosarcoma. Cytologically, tumour cells form dyscohesive clusters, with comparatively monomorphous round nuclei and scant cytoplasm.
Alveolar rhabdomyosarcoma. Detection of PAX3-FOXO1 fusion gene by RT-PCR and direct sequencing.
Alveolar rhabdomyosarcoma. Interphase FISH analysis showing amplification of the PAX7-FOXO1 fusion gene (juxtaposed red and green signals) by 1;13 translocation breakpoint-flanking probes.
Wildtype and fusion products associated with 2;13 and 1;13 translocations. The paired box (PB), octapeptide, homeobox domain (HD), and forkhead domain (FD) are shown as grey boxes. Transcriptional domains (DNA-binding domain [DBD] and transcriptional activation domain [TAD]) are indicated as solid horizontal bars. The translocation fusion point is shown as a vertical dashed line.
Rhabdomyosarcoma with embryonal and alveolar components. Foci of small round tumour cells and differentiating rhabdomyoblasts. Most of these tumours lack the presence of a FOXO1-related fusion and probably represent embryonal rhabdomyosarcoma.

Q: The prototypical histologic appearance of Ectomesenchymoma consists of an intimate admixture of embryonal rhabdomyosarcoma and [...] elements (ranging from primitive cells to mature ganglion cells).
Ectomesenchymoma. This example shows rhabdomyosarcoma of spindle cell morphology with scattered neurons.
Ectomesenchymoma. Intimate and composite growth of embryonal rhabdomyosarcoma and ganglioneuroblastoma is seen in this ectomesenchymoma. The former is evident by myogenin immunoreactivity (shown in Fig. #6075).
A: neuroblastic
Back Extra: Ectomesenchymoma
- Clinical: Ectomesenchymomas are rare, primarily affecting infants and children under 5 years with a slight male predominance.
- Micro: The prototypical morphology consists of embryonal rhabdomyosarcoma intermixed with neuroblastic elements, ranging from scattered ganglion cells to primitive neuroblasts.
- Ancillary: Cytogenetic findings often show trisomies of chromosomes 2, 8, and 11, similar to those in embryonal rhabdomyosarcoma.
Reference Gallery:
Ectomesenchymoma. This example shows rhabdomyosarcoma of spindle cell morphology with scattered neurons.
Ectomesenchymoma. Intimate and composite growth of embryonal rhabdomyosarcoma and ganglioneuroblastoma is seen in this ectomesenchymoma. The former is evident by myogenin immunoreactivity (shown in Fig. #6075).
Ectomesenchymoma. Intimate and composite growth of embryonal rhabdomyosarcoma and ganglioneuroblastoma is seen in this ectomesenchymoma (shown in Fig. #6074). The former is evident by myogenin immunoreactivity (shown here).

Q: In Ectomesenchymoma, the embryonal rhabdomyosarcoma component can be confirmed by strong nuclear immunoreactivity for the skeletal muscle marker [...].
Ectomesenchymoma. Intimate and composite growth of embryonal rhabdomyosarcoma and ganglioneuroblastoma is seen in this ectomesenchymoma (shown in Fig. #6074). The former is evident by myogenin immunoreactivity (shown here).
A: myogenin
Back Extra: Ectomesenchymoma
- Clinical: Ectomesenchymomas are rare, primarily affecting infants and children under 5 years with a slight male predominance.
- Micro: The prototypical morphology consists of embryonal rhabdomyosarcoma intermixed with neuroblastic elements, ranging from scattered ganglion cells to primitive neuroblasts.
- Ancillary: Cytogenetic findings often show trisomies of chromosomes 2, 8, and 11, similar to those in embryonal rhabdomyosarcoma.
Reference Gallery:
Ectomesenchymoma. This example shows rhabdomyosarcoma of spindle cell morphology with scattered neurons.
Ectomesenchymoma. Intimate and composite growth of embryonal rhabdomyosarcoma and ganglioneuroblastoma is seen in this ectomesenchymoma. The former is evident by myogenin immunoreactivity (shown in Fig. #6075).
Ectomesenchymoma. Intimate and composite growth of embryonal rhabdomyosarcoma and ganglioneuroblastoma is seen in this ectomesenchymoma (shown in Fig. #6074). The former is evident by myogenin immunoreactivity (shown here).

Q: Histologically, Embryonal Rhabdomyosarcoma frequently demonstrates alternating areas of loose (myxoid) and dense cellularity containing primitive cells and variably differentiated [...].
Embryonal rhabdomyosarcoma. The typical histological pattern of embryonal rhabdomyosarcomas recapitulates skeletal muscle development, with alternating areas of loose and dense cellularity.
Embryonal rhabdomyosarcoma, botryoid subtype. Primitive round to slightly spindled cells with several differentiating rhabdomyoblasts.
A: rhabdomyoblasts
Back Extra: Embryonal Rhabdomyosarcoma
- Clinical: Embryonal rhabdomyosarcoma (ERMS) commonly presents in the head and neck region or genitourinary system, often causing proptosis or urinary retention.
- Micro: ERMS is characterized by variably differentiated rhabdomyoblasts within a loose, myxoid mesenchyme, with alternating areas of dense and loose cellularity.
- Ancillary: Immunohistochemistry shows positivity for desmin, myogenin, and MYOD1, and genomic studies often reveal RAS pathway mutations.
Reference Gallery:
Botryoid embryonal rhabdomyosarcoma. Gross photograph of a botryoid embryonal rhabdomyosarcoma showing multiple polypoid clusters of tumour.
Embryonal rhabdomyosarcoma, botryoid subtype. Low-power microscopy. Histologically, the botryoid pattern of embryonal rhabdomyosarcoma shows a variably cellular tumour with a myxoid background and condensation of nuclei beneath an epithelial surface.
Dense embryonal rhabdomyosarcoma. This pattern with sheets of round cells may show similarity to the solid pattern of alveolar rhabdomyosarcoma.
Embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma in this example is composed of short, irregular fascicles of ovoid to spindled cells with focal myotube formation.
Orbital embryonal rhabdomyosarcoma. An orbital embryonal rhabdomyosarcoma with a fleshy, pale-tan cut surface that resulted in proptosis of the overlying globe.
Embryonal rhabdomyosarcoma. The typical histological pattern of embryonal rhabdomyosarcomas recapitulates skeletal muscle development, with alternating areas of loose and dense cellularity.
Anaplastic embryonal rhabdomyosarcoma. Poorly differentiated appearance with a large, atypical mitotic figure.
Embryonal rhabdomyosarcoma, botryoid subtype. This tumour presented as a polypoid submucosal mass in the bladder of a boy.
Embryonal rhabdomyosarcoma, botryoid subtype. Primitive round to slightly spindled cells with several differentiating rhabdomyoblasts.

Q: The [...] variant of Embryonal Rhabdomyosarcoma classically presents as a gross polypoid (grape-like) mass projecting into a mucosal lumen, such as the urinary bladder.
Botryoid embryonal rhabdomyosarcoma. Gross photograph of a botryoid embryonal rhabdomyosarcoma showing multiple polypoid clusters of tumour.
Embryonal rhabdomyosarcoma, botryoid subtype. This tumour presented as a polypoid submucosal mass in the bladder of a boy.
A: botryoid
Back Extra: Embryonal Rhabdomyosarcoma
- Clinical: Embryonal rhabdomyosarcoma (ERMS) commonly presents in the head and neck region or genitourinary system, often causing proptosis or urinary retention.
- Micro: ERMS is characterized by variably differentiated rhabdomyoblasts within a loose, myxoid mesenchyme, with alternating areas of dense and loose cellularity.
- Ancillary: Immunohistochemistry shows positivity for desmin, myogenin, and MYOD1, and genomic studies often reveal RAS pathway mutations.
Reference Gallery:
Botryoid embryonal rhabdomyosarcoma. Gross photograph of a botryoid embryonal rhabdomyosarcoma showing multiple polypoid clusters of tumour.
Embryonal rhabdomyosarcoma, botryoid subtype. Low-power microscopy. Histologically, the botryoid pattern of embryonal rhabdomyosarcoma shows a variably cellular tumour with a myxoid background and condensation of nuclei beneath an epithelial surface.
Dense embryonal rhabdomyosarcoma. This pattern with sheets of round cells may show similarity to the solid pattern of alveolar rhabdomyosarcoma.
Embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma in this example is composed of short, irregular fascicles of ovoid to spindled cells with focal myotube formation.
Orbital embryonal rhabdomyosarcoma. An orbital embryonal rhabdomyosarcoma with a fleshy, pale-tan cut surface that resulted in proptosis of the overlying globe.
Embryonal rhabdomyosarcoma. The typical histological pattern of embryonal rhabdomyosarcomas recapitulates skeletal muscle development, with alternating areas of loose and dense cellularity.
Anaplastic embryonal rhabdomyosarcoma. Poorly differentiated appearance with a large, atypical mitotic figure.
Embryonal rhabdomyosarcoma, botryoid subtype. This tumour presented as a polypoid submucosal mass in the bladder of a boy.
Embryonal rhabdomyosarcoma, botryoid subtype. Primitive round to slightly spindled cells with several differentiating rhabdomyoblasts.

Q: A fleshy, pale-tan orbital mass causing proptosis of the overlying globe in a pediatric patient is highly suspicious for [...].
Orbital embryonal rhabdomyosarcoma. An orbital embryonal rhabdomyosarcoma with a fleshy, pale-tan cut surface that resulted in proptosis of the overlying globe.
A: Embryonal Rhabdomyosarcoma
Back Extra: Embryonal Rhabdomyosarcoma
- Clinical: Embryonal rhabdomyosarcoma (ERMS) commonly presents in the head and neck region or genitourinary system, often causing proptosis or urinary retention.
- Micro: ERMS is characterized by variably differentiated rhabdomyoblasts within a loose, myxoid mesenchyme, with alternating areas of dense and loose cellularity.
- Ancillary: Immunohistochemistry shows positivity for desmin, myogenin, and MYOD1, and genomic studies often reveal RAS pathway mutations.
Reference Gallery:
Botryoid embryonal rhabdomyosarcoma. Gross photograph of a botryoid embryonal rhabdomyosarcoma showing multiple polypoid clusters of tumour.
Embryonal rhabdomyosarcoma, botryoid subtype. Low-power microscopy. Histologically, the botryoid pattern of embryonal rhabdomyosarcoma shows a variably cellular tumour with a myxoid background and condensation of nuclei beneath an epithelial surface.
Dense embryonal rhabdomyosarcoma. This pattern with sheets of round cells may show similarity to the solid pattern of alveolar rhabdomyosarcoma.
Embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma in this example is composed of short, irregular fascicles of ovoid to spindled cells with focal myotube formation.
Orbital embryonal rhabdomyosarcoma. An orbital embryonal rhabdomyosarcoma with a fleshy, pale-tan cut surface that resulted in proptosis of the overlying globe.
Embryonal rhabdomyosarcoma. The typical histological pattern of embryonal rhabdomyosarcomas recapitulates skeletal muscle development, with alternating areas of loose and dense cellularity.
Anaplastic embryonal rhabdomyosarcoma. Poorly differentiated appearance with a large, atypical mitotic figure.
Embryonal rhabdomyosarcoma, botryoid subtype. This tumour presented as a polypoid submucosal mass in the bladder of a boy.
Embryonal rhabdomyosarcoma, botryoid subtype. Primitive round to slightly spindled cells with several differentiating rhabdomyoblasts.

Q: Characterized by large, atypical cells with eosinophilic cytoplasm, severe nuclear pleomorphism, and prominent macronucleoli, [...] is a high-grade soft tissue tumor most commonly arising in the deep soft tissues of older adults.
Pleomorphic rhabdomyosarcoma. Note the nuclear pleomorphism. A malignant cell in the centre of the image appears to have cannibalized another cell. There is an atypical mitosis at the upper right.
Pleomorphic rhabdomyosarcoma. There is striking variability in the sizes and shapes of the nuclei, and many feature macronucleoli.
A: Pleomorphic Rhabdomyosarcoma
Back Extra: Pleomorphic Rhabdomyosarcoma
- Clinical: Patients typically present with a rapidly growing, deep, and variably painful soft tissue swelling, most commonly in the sixth to seventh decades of life.
- Micro: The tumour is characterized by sheets of large, atypical cells with eosinophilic cytoplasm, displaying significant nuclear pleomorphism, macronucleoli, and atypical mitoses.
- Ancillary: Immunohistochemical studies show strong desmin expression and often limited expression of MYOD1 and myogenin, crucial for confirming the diagnosis.
Reference Gallery:
Pleomorphic rhabdomyosarcoma. In this gross image, a firm and centrally necrotic tumour is present in the subcutaneous adipose tissue, although such lesions are frequently deep.
Pleomorphic rhabdomyosarcoma. Several of the cells in this image feature macronucleoli.
Pleomorphic rhabdomyosarcoma. Note the nuclear pleomorphism. A malignant cell in the centre of the image appears to have cannibalized another cell. There is an atypical mitosis at the upper right.
Pleomorphic rhabdomyosarcoma. This needle biopsy specimen from a deep thigh mass shows striking nuclear pleomorphism at low magnification.
Pleomorphic rhabdomyosarcoma. There is striking variability in the sizes and shapes of the nuclei, and many feature macronucleoli.
Pleomorphic rhabdomyosarcoma. These tumours are generally diffusely reactive with desmin antibodies.
Pleomorphic rhabdomyosarcoma. Myogenin immunostaining. Not every cell is immunolabelled, but the pattern depicted here is sufficient to confirm the diagnosis.

Q: To confirm a diagnosis of Pleomorphic Rhabdomyosarcoma, immunohistochemistry typically demonstrates strong, diffuse reactivity for [...], alongside more limited or focal expression of skeletal muscle markers like MYOD1 and myogenin.
Pleomorphic rhabdomyosarcoma. These tumours are generally diffusely reactive with desmin antibodies.
Pleomorphic rhabdomyosarcoma. Myogenin immunostaining. Not every cell is immunolabelled, but the pattern depicted here is sufficient to confirm the diagnosis.
A: desmin
Back Extra: Pleomorphic Rhabdomyosarcoma
- Clinical: Patients typically present with a rapidly growing, deep, and variably painful soft tissue swelling, most commonly in the sixth to seventh decades of life.
- Micro: The tumour is characterized by sheets of large, atypical cells with eosinophilic cytoplasm, displaying significant nuclear pleomorphism, macronucleoli, and atypical mitoses.
- Ancillary: Immunohistochemical studies show strong desmin expression and often limited expression of MYOD1 and myogenin, crucial for confirming the diagnosis.
Reference Gallery:
Pleomorphic rhabdomyosarcoma. In this gross image, a firm and centrally necrotic tumour is present in the subcutaneous adipose tissue, although such lesions are frequently deep.
Pleomorphic rhabdomyosarcoma. Several of the cells in this image feature macronucleoli.
Pleomorphic rhabdomyosarcoma. Note the nuclear pleomorphism. A malignant cell in the centre of the image appears to have cannibalized another cell. There is an atypical mitosis at the upper right.
Pleomorphic rhabdomyosarcoma. This needle biopsy specimen from a deep thigh mass shows striking nuclear pleomorphism at low magnification.
Pleomorphic rhabdomyosarcoma. There is striking variability in the sizes and shapes of the nuclei, and many feature macronucleoli.
Pleomorphic rhabdomyosarcoma. These tumours are generally diffusely reactive with desmin antibodies.
Pleomorphic rhabdomyosarcoma. Myogenin immunostaining. Not every cell is immunolabelled, but the pattern depicted here is sufficient to confirm the diagnosis.

Q: Histologically, the sclerosing variant of Spindle Cell / Sclerosing Rhabdomyosarcoma is characterized by tumor cells embedded in a prominent hyalinized, sclerotic background, frequently arranging in a characteristic [...] pattern.
Sclerosing rhabdomyosarcoma. Clusters of tumour cells in a sclerotic collagenous background.
Sclerosing rhabdomyosarcoma. Pseudovascular pattern of arrangement of the tumour cells.
A: pseudovascular
Back Extra: Spindle Cell / Sclerosing Rhabdomyosarcoma
- Clinical: Spindle cell / sclerosing rhabdomyosarcoma typically presents as a rapidly growing, painless soft tissue mass, often affecting infants, children, and adults, with the head and neck region being the most common site.
- Micro: Spindle cell rhabdomyosarcoma shows cellular fascicles of spindle cells with an intersecting or herringbone growth pattern, while sclerosing rhabdomyosarcoma shows prominent hyalinization/sclerosis and a pseudovascular arrangement of tumour cells.
- Ancillary: Immunohistochemically, spindle cell / sclerosing rhabdomyosarcoma is characterized by diffuse expression of desmin and focal or diffuse expression of MYOD1, with MYF4 (myogenin) showing focal positivity.
Reference Gallery:
Spindle cell rhabdomyosarcoma. Spindle cell rhabdomyosarcoma composed of uniform spindle cells in a fascicular pattern.
Spindle cell rhabdomyosarcoma. Immunohistochemical staining for desmin showing diffuse positivity in the tumour cells.
Spindle cell rhabdomyosarcoma. Myogenin staining showing focal positivity.
Spindle cell rhabdomyosarcoma. MYOD1 staining showing diffuse positivity.
Sclerosing rhabdomyosarcoma. Clusters of tumour cells in a sclerotic collagenous background.
Sclerosing rhabdomyosarcoma. Pseudovascular pattern of arrangement of the tumour cells.
Spindle cell rhabdomyosarcoma. MYOD1 p.Leu122Arg homozygous mutation represented on direct sequencing.
Spindle cell rhabdomyosarcoma. Gross image showing a well-circumscribed tumour with tan-yellow cut surface with central necrosis, involving soft tissue and abutting the bone.

Q: The spindle cell variant of Spindle Cell / Sclerosing Rhabdomyosarcoma typically consists of uniform spindle cells arranged in cellular fascicles with an intersecting or [...] growth pattern.
Spindle cell rhabdomyosarcoma. Spindle cell rhabdomyosarcoma composed of uniform spindle cells in a fascicular pattern.
A: herringbone
Back Extra: Spindle Cell / Sclerosing Rhabdomyosarcoma
- Clinical: Spindle cell / sclerosing rhabdomyosarcoma typically presents as a rapidly growing, painless soft tissue mass, often affecting infants, children, and adults, with the head and neck region being the most common site.
- Micro: Spindle cell rhabdomyosarcoma shows cellular fascicles of spindle cells with an intersecting or herringbone growth pattern, while sclerosing rhabdomyosarcoma shows prominent hyalinization/sclerosis and a pseudovascular arrangement of tumour cells.
- Ancillary: Immunohistochemically, spindle cell / sclerosing rhabdomyosarcoma is characterized by diffuse expression of desmin and focal or diffuse expression of MYOD1, with MYF4 (myogenin) showing focal positivity.
Reference Gallery:
Spindle cell rhabdomyosarcoma. Spindle cell rhabdomyosarcoma composed of uniform spindle cells in a fascicular pattern.
Spindle cell rhabdomyosarcoma. Immunohistochemical staining for desmin showing diffuse positivity in the tumour cells.
Spindle cell rhabdomyosarcoma. Myogenin staining showing focal positivity.
Spindle cell rhabdomyosarcoma. MYOD1 staining showing diffuse positivity.
Sclerosing rhabdomyosarcoma. Clusters of tumour cells in a sclerotic collagenous background.
Sclerosing rhabdomyosarcoma. Pseudovascular pattern of arrangement of the tumour cells.
Spindle cell rhabdomyosarcoma. MYOD1 p.Leu122Arg homozygous mutation represented on direct sequencing.
Spindle cell rhabdomyosarcoma. Gross image showing a well-circumscribed tumour with tan-yellow cut surface with central necrosis, involving soft tissue and abutting the bone.

Q: A soft tissue tumor demonstrating diffuse immunohistochemical positivity for desmin and MYOD1, but only focal positivity for myogenin (MYF4), is highly characteristic of [...].
Spindle cell rhabdomyosarcoma. Immunohistochemical staining for desmin showing diffuse positivity in the tumour cells.
Spindle cell rhabdomyosarcoma. Myogenin staining showing focal positivity.
Spindle cell rhabdomyosarcoma. MYOD1 staining showing diffuse positivity.
A: Spindle Cell / Sclerosing Rhabdomyosarcoma
Back Extra: Spindle Cell / Sclerosing Rhabdomyosarcoma
- Clinical: Spindle cell / sclerosing rhabdomyosarcoma typically presents as a rapidly growing, painless soft tissue mass, often affecting infants, children, and adults, with the head and neck region being the most common site.
- Micro: Spindle cell rhabdomyosarcoma shows cellular fascicles of spindle cells with an intersecting or herringbone growth pattern, while sclerosing rhabdomyosarcoma shows prominent hyalinization/sclerosis and a pseudovascular arrangement of tumour cells.
- Ancillary: Immunohistochemically, spindle cell / sclerosing rhabdomyosarcoma is characterized by diffuse expression of desmin and focal or diffuse expression of MYOD1, with MYF4 (myogenin) showing focal positivity.
Reference Gallery:
Spindle cell rhabdomyosarcoma. Spindle cell rhabdomyosarcoma composed of uniform spindle cells in a fascicular pattern.
Spindle cell rhabdomyosarcoma. Immunohistochemical staining for desmin showing diffuse positivity in the tumour cells.
Spindle cell rhabdomyosarcoma. Myogenin staining showing focal positivity.
Spindle cell rhabdomyosarcoma. MYOD1 staining showing diffuse positivity.
Sclerosing rhabdomyosarcoma. Clusters of tumour cells in a sclerotic collagenous background.
Sclerosing rhabdomyosarcoma. Pseudovascular pattern of arrangement of the tumour cells.
Spindle cell rhabdomyosarcoma. MYOD1 p.Leu122Arg homozygous mutation represented on direct sequencing.
Spindle cell rhabdomyosarcoma. Gross image showing a well-circumscribed tumour with tan-yellow cut surface with central necrosis, involving soft tissue and abutting the bone.

Q: The development of an EBV-associated smooth muscle tumor is strongly linked to patients who are severely [...], particularly those with HIV/AIDS or a history of organ transplantation.
EBV-associated smooth muscle tumour. Gross autopsy photograph of multiple splenic tumours in a child who underwent haematopoietic stem cell transplantation for a primary immune disorder 10 months earlier; a monomorphic B-cell posttransplant lymphoproliferative disorder was found concurrently in the liver.
A: immunocompromised
Back Extra: EBV-associated smooth muscle tumour
- Clinical: EBV-associated smooth muscle tumours most commonly occur in immunocompromised patients, particularly those with HIV/AIDS, post-transplant, or primary immunodeficiency.
- Micro: The tumour is characterized by intersecting fascicles of spindled cells with ample eosinophilic cytoplasm and elongated nuclei, often accompanied by a second population of round, more primitive-appearing cells.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is consistently positive in the neoplastic cells.
Reference Gallery:
EBV-associated smooth muscle tumour. Gross autopsy photograph of multiple splenic tumours in a child who underwent haematopoietic stem cell transplantation for a primary immune disorder 10 months earlier; a monomorphic B-cell posttransplant lymphoproliferative disorder was found concurrently in the liver.
EBV-associated smooth muscle tumour. Whole-mount section of EBV-associated smooth muscle tumour developing in penile skin (scale bar = 500 μm).
EBV-associated smooth muscle tumour. Intersecting fascicles of spindled cells with ample eosinophilic cytoplasm and elongated nuclei.
EBV-associated smooth muscle tumour. Round cells with a more primitive appearance accompany the spindled cells in about one half of cases.
EBV-associated smooth muscle tumour. The nuclei are positive with in situ hybridization for EBV-encoded small RNA (EBER).
EBV-associated smooth muscle tumour. T cells are commonly found within the tumour, although they are usually sparse.

Q: Microscopically, an EBV-associated smooth muscle tumor typically exhibits intersecting fascicles of spindled cells, frequently accompanied by a secondary population of more primitive-appearing [...] cells.
EBV-associated smooth muscle tumour. Intersecting fascicles of spindled cells with ample eosinophilic cytoplasm and elongated nuclei.
EBV-associated smooth muscle tumour. Round cells with a more primitive appearance accompany the spindled cells in about one half of cases.
A: round
Back Extra: EBV-associated smooth muscle tumour
- Clinical: EBV-associated smooth muscle tumours most commonly occur in immunocompromised patients, particularly those with HIV/AIDS, post-transplant, or primary immunodeficiency.
- Micro: The tumour is characterized by intersecting fascicles of spindled cells with ample eosinophilic cytoplasm and elongated nuclei, often accompanied by a second population of round, more primitive-appearing cells.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is consistently positive in the neoplastic cells.
Reference Gallery:
EBV-associated smooth muscle tumour. Gross autopsy photograph of multiple splenic tumours in a child who underwent haematopoietic stem cell transplantation for a primary immune disorder 10 months earlier; a monomorphic B-cell posttransplant lymphoproliferative disorder was found concurrently in the liver.
EBV-associated smooth muscle tumour. Whole-mount section of EBV-associated smooth muscle tumour developing in penile skin (scale bar = 500 μm).
EBV-associated smooth muscle tumour. Intersecting fascicles of spindled cells with ample eosinophilic cytoplasm and elongated nuclei.
EBV-associated smooth muscle tumour. Round cells with a more primitive appearance accompany the spindled cells in about one half of cases.
EBV-associated smooth muscle tumour. The nuclei are positive with in situ hybridization for EBV-encoded small RNA (EBER).
EBV-associated smooth muscle tumour. T cells are commonly found within the tumour, although they are usually sparse.

Q: The definitive ancillary test for an EBV-associated smooth muscle tumor demonstrates consistently positive nuclear staining utilizing in situ hybridization for [...].
EBV-associated smooth muscle tumour. The nuclei are positive with in situ hybridization for EBV-encoded small RNA (EBER).
A: EBER
Back Extra: EBV-associated smooth muscle tumour
- Clinical: EBV-associated smooth muscle tumours most commonly occur in immunocompromised patients, particularly those with HIV/AIDS, post-transplant, or primary immunodeficiency.
- Micro: The tumour is characterized by intersecting fascicles of spindled cells with ample eosinophilic cytoplasm and elongated nuclei, often accompanied by a second population of round, more primitive-appearing cells.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is consistently positive in the neoplastic cells.
Reference Gallery:
EBV-associated smooth muscle tumour. Gross autopsy photograph of multiple splenic tumours in a child who underwent haematopoietic stem cell transplantation for a primary immune disorder 10 months earlier; a monomorphic B-cell posttransplant lymphoproliferative disorder was found concurrently in the liver.
EBV-associated smooth muscle tumour. Whole-mount section of EBV-associated smooth muscle tumour developing in penile skin (scale bar = 500 μm).
EBV-associated smooth muscle tumour. Intersecting fascicles of spindled cells with ample eosinophilic cytoplasm and elongated nuclei.
EBV-associated smooth muscle tumour. Round cells with a more primitive appearance accompany the spindled cells in about one half of cases.
EBV-associated smooth muscle tumour. The nuclei are positive with in situ hybridization for EBV-encoded small RNA (EBER).
EBV-associated smooth muscle tumour. T cells are commonly found within the tumour, although they are usually sparse.

Q: Microscopically, a Leiomyoma is composed of cells with eosinophilic cytoplasm and uniform, blunt-ended, [...] nuclei arranged in orderly intersecting fascicles.
Leiomyoma. Higher magnification of leiomyoma of somatic soft tissue, showing fascicles of smooth muscle cells.
Leiomyoma. Low-power view shows clear distinction from surrounding tissue and broad interlacing fascicles of smooth muscle cells.
A: cigar-shaped
Back Extra: Leiomyoma
- Clinical: Leiomyomas are usually solitary, but retroperitoneal tumours may be multiple. Somatic tumours often have calcification and are detected radiographically.
- Micro: Leiomyomas of deep soft tissue are composed of cells that closely resemble normal smooth muscle cells with eosinophilic cytoplasm and uniform blunt-ended, cigar-shaped nuclei, arranged in orderly intersecting fascicles.
- Ancillary: Tumour cells are positive for SMA, desmin, and h-caldesmon, but negative for S100. Retroperitoneal leiomyomas are almost always positive for ER, PR, and WT1.
Reference Gallery:
Leiomyoma. Higher magnification of leiomyoma of somatic soft tissue, showing fascicles of smooth muscle cells.
Leiomyoma. Retroperitoneal leiomyoma with myxoid change.
Leiomyoma. Retroperitoneal leiomyoma with hyalinization.
Retroperitoneal leiomyoma. The tumour nuclei are diffusely positive for ER, typical of retroperitoneal leiomyomas.
Retroperitoneal leiomyoma with hydropic change. Retroperitoneal leiomyoma composed of thin fascicles of bland smooth muscle separated by an oedematous stroma. Hydropic change is often seen in retroperitoneal leiomyomas.
Leiomyoma. Low-power view shows clear distinction from surrounding tissue and broad interlacing fascicles of smooth muscle cells.

Q: Immunohistochemically, a retroperitoneal Leiomyoma is almost always positive for PR, WT1, and [...], which is often diffusely expressed in the tumor nuclei.
Retroperitoneal leiomyoma. The tumour nuclei are diffusely positive for ER, typical of retroperitoneal leiomyomas.
A: ER
Back Extra: Leiomyoma
- Clinical: Leiomyomas are usually solitary, but retroperitoneal tumours may be multiple. Somatic tumours often have calcification and are detected radiographically.
- Micro: Leiomyomas of deep soft tissue are composed of cells that closely resemble normal smooth muscle cells with eosinophilic cytoplasm and uniform blunt-ended, cigar-shaped nuclei, arranged in orderly intersecting fascicles.
- Ancillary: Tumour cells are positive for SMA, desmin, and h-caldesmon, but negative for S100. Retroperitoneal leiomyomas are almost always positive for ER, PR, and WT1.
Reference Gallery:
Leiomyoma. Higher magnification of leiomyoma of somatic soft tissue, showing fascicles of smooth muscle cells.
Leiomyoma. Retroperitoneal leiomyoma with myxoid change.
Leiomyoma. Retroperitoneal leiomyoma with hyalinization.
Retroperitoneal leiomyoma. The tumour nuclei are diffusely positive for ER, typical of retroperitoneal leiomyomas.
Retroperitoneal leiomyoma with hydropic change. Retroperitoneal leiomyoma composed of thin fascicles of bland smooth muscle separated by an oedematous stroma. Hydropic change is often seen in retroperitoneal leiomyomas.
Leiomyoma. Low-power view shows clear distinction from surrounding tissue and broad interlacing fascicles of smooth muscle cells.

Q: A retroperitoneal Leiomyoma often exhibits secondary stromal changes, such as hyalinization, myxoid change, or an edematous stroma referred to as [...] change.
Leiomyoma. Retroperitoneal leiomyoma with myxoid change.
Leiomyoma. Retroperitoneal leiomyoma with hyalinization.
Retroperitoneal leiomyoma with hydropic change. Retroperitoneal leiomyoma composed of thin fascicles of bland smooth muscle separated by an oedematous stroma. Hydropic change is often seen in retroperitoneal leiomyomas.
A: hydropic
Back Extra: Leiomyoma
- Clinical: Leiomyomas are usually solitary, but retroperitoneal tumours may be multiple. Somatic tumours often have calcification and are detected radiographically.
- Micro: Leiomyomas of deep soft tissue are composed of cells that closely resemble normal smooth muscle cells with eosinophilic cytoplasm and uniform blunt-ended, cigar-shaped nuclei, arranged in orderly intersecting fascicles.
- Ancillary: Tumour cells are positive for SMA, desmin, and h-caldesmon, but negative for S100. Retroperitoneal leiomyomas are almost always positive for ER, PR, and WT1.
Reference Gallery:
Leiomyoma. Higher magnification of leiomyoma of somatic soft tissue, showing fascicles of smooth muscle cells.
Leiomyoma. Retroperitoneal leiomyoma with myxoid change.
Leiomyoma. Retroperitoneal leiomyoma with hyalinization.
Retroperitoneal leiomyoma. The tumour nuclei are diffusely positive for ER, typical of retroperitoneal leiomyomas.
Retroperitoneal leiomyoma with hydropic change. Retroperitoneal leiomyoma composed of thin fascicles of bland smooth muscle separated by an oedematous stroma. Hydropic change is often seen in retroperitoneal leiomyomas.
Leiomyoma. Low-power view shows clear distinction from surrounding tissue and broad interlacing fascicles of smooth muscle cells.

Q: Microscopic examination of [...] characteristically reveals spindled tumor cells (often highlighted by desmin) that are largely obscured by a prominent infiltrate of small lymphocytes and xanthomatous histiocytes.
Inflammatory leiomyosarcoma. Tumour cells are largely obscured by the prominent lymphoid infiltrate.
Inflammatory leiomyosarcoma. In this tumour there is a mixed lymphohistiocytic infiltrate with prominent xanthomatous cells.
Inflammatory leiomyosarcoma. Between numerous lymphohistiocytic cells, the spindled tumour cells are highlighted by immunopositivity for desmin.
A: Inflammatory Leiomyosarcoma
Back Extra: Inflammatory Leiomyosarcoma
- Clinical: Most cases of inflammatory leiomyosarcoma present as an enlarging deep soft tissue mass, often with no specific features, and are associated with a relative male predominance.
- Micro: The characteristic feature of inflammatory leiomyosarcoma is the presence of a prominent inflammatory infiltrate, often dominated by small lymphocytes and histiocytes, which may have a xanthomatous appearance.
- Ancillary: The near-haploid genotype is a distinctive feature of inflammatory leiomyosarcoma, with retention of heterozygosity for chromosomes 5, 18, 20, 21, and 22.
Reference Gallery:
Inflammatory leiomyosarcoma. Tumour cells are largely obscured by the prominent lymphoid infiltrate.
Inflammatory leiomyosarcoma. In this tumour there is a mixed lymphohistiocytic infiltrate with prominent xanthomatous cells.
Inflammatory leiomyosarcoma. Between numerous lymphohistiocytic cells, the spindled tumour cells are highlighted by immunopositivity for desmin.
Inflammatory leiomyosarcoma. Genomic array findings in an inflammatory leiomyosarcoma showing relative copy-number gain of chromosomes 5, 18, and 20–22 (top, red) and loss of heterozygosity for all other chromosomes (bottom, grey).

Q: The distinctive ancillary finding in Inflammatory Leiomyosarcoma is a [...] with retention of heterozygosity for chromosomes 5, 18, 20, 21, and 22.
Inflammatory leiomyosarcoma. Genomic array findings in an inflammatory leiomyosarcoma showing relative copy-number gain of chromosomes 5, 18, and 20–22 (top, red) and loss of heterozygosity for all other chromosomes (bottom, grey).
A: near-haploid genotype
Back Extra: Inflammatory Leiomyosarcoma
- Clinical: Most cases of inflammatory leiomyosarcoma present as an enlarging deep soft tissue mass, often with no specific features, and are associated with a relative male predominance.
- Micro: The characteristic feature of inflammatory leiomyosarcoma is the presence of a prominent inflammatory infiltrate, often dominated by small lymphocytes and histiocytes, which may have a xanthomatous appearance.
- Ancillary: The near-haploid genotype is a distinctive feature of inflammatory leiomyosarcoma, with retention of heterozygosity for chromosomes 5, 18, 20, 21, and 22.
Reference Gallery:
Inflammatory leiomyosarcoma. Tumour cells are largely obscured by the prominent lymphoid infiltrate.
Inflammatory leiomyosarcoma. In this tumour there is a mixed lymphohistiocytic infiltrate with prominent xanthomatous cells.
Inflammatory leiomyosarcoma. Between numerous lymphohistiocytic cells, the spindled tumour cells are highlighted by immunopositivity for desmin.
Inflammatory leiomyosarcoma. Genomic array findings in an inflammatory leiomyosarcoma showing relative copy-number gain of chromosomes 5, 18, and 20–22 (top, red) and loss of heterozygosity for all other chromosomes (bottom, grey).

Q: Histologically, Leiomyosarcoma frequently exhibits intersecting fascicles of spindle cells with abundant eosinophilic cytoplasm and characteristic plump, [...] nuclei.
Leiomyosarcoma. Leiomyosarcoma showing fascicles of spindle cells with hyperchromatic nuclei with scattered moderate pleomorphism and abundant eosinophilic cytoplasm.
Leiomyosarcoma. Intermediate-grade leiomyosarcoma. The tumour cells show classic features of smooth muscle differentiation, with variably pleomorphic, elongated nuclei; perinuclear vacuoles; and distinctly eosinophilic cytoplasm.
A: blunt-ended
Back Extra: Leiomyosarcoma
- Clinical: Leiomyosarcoma often presents as a mass lesion with nonspecific symptoms, especially when located in the retroperitoneum or large vessels.
- Micro: Leiomyosarcoma shows spindle-shaped cells with plump, blunt-ended nuclei and abundant eosinophilic cytoplasm, arranged in long intersecting fascicles.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with at least one myogenic marker (SMA, desmin, h-caldesmon) positive in 100% of cases.
Reference Gallery:
Leiomyosarcoma. Leiomyosarcoma showing fascicles of spindle cells with hyperchromatic nuclei with scattered moderate pleomorphism and abundant eosinophilic cytoplasm.
Leiomyosarcoma with myxoid matrix. Myxoid change in soft tissue leiomyosarcomas is unusual but may be seen.
Leiomyosarcoma. Leiomyosarcoma arising from the inferior vena cava.
Leiomyosarcoma. Low-grade leiomyosarcoma, composed of well-differentiated smooth muscle, with nuclear hyperchromatism and identifiable mitotic activity.
Leiomyosarcoma. Intermediate-grade leiomyosarcoma, arising from the wall of a vein. Many soft tissue leiomyosarcomas arise from vascular smooth muscle, and such tumours may be deceptively well circumscribed.
Leiomyosarcoma. Intermediate-grade leiomyosarcoma. The tumour cells show classic features of smooth muscle differentiation, with variably pleomorphic, elongated nuclei; perinuclear vacuoles; and distinctly eosinophilic cytoplasm.
Leiomyosarcoma. Low-grade leiomyosarcoma with granular cell change. Leiomyosarcomas with this unusual morphological feature may be confused with granular cell tumours.
Leiomyosarcoma. Dedifferentiated leiomyosarcoma, showing an abrupt transition from conventional grade 2 leiomyosarcoma to an essentially undifferentiated-appearing pleomorphic sarcoma. These undifferentiated areas lacked expression of muscle markers.
Leiomyosarcoma. Axial contrast-enhanced CT shows a right-sided retroperitoneal mass (solid arrow), which is clearly arising from the inferior vena cava. The lumen of the inferior vena cava is partially occluded (slit-like residual lumen indicated by dashed arrow).

Q: Retroperitoneal Leiomyosarcoma has a distinct propensity to arise directly from large blood vessels, most classically the [...].
Leiomyosarcoma. Leiomyosarcoma arising from the inferior vena cava.
Leiomyosarcoma. Axial contrast-enhanced CT shows a right-sided retroperitoneal mass (solid arrow), which is clearly arising from the inferior vena cava. The lumen of the inferior vena cava is partially occluded (slit-like residual lumen indicated by dashed arrow).
A: inferior vena cava
Back Extra: Leiomyosarcoma
- Clinical: Leiomyosarcoma often presents as a mass lesion with nonspecific symptoms, especially when located in the retroperitoneum or large vessels.
- Micro: Leiomyosarcoma shows spindle-shaped cells with plump, blunt-ended nuclei and abundant eosinophilic cytoplasm, arranged in long intersecting fascicles.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with at least one myogenic marker (SMA, desmin, h-caldesmon) positive in 100% of cases.
Reference Gallery:
Leiomyosarcoma. Leiomyosarcoma showing fascicles of spindle cells with hyperchromatic nuclei with scattered moderate pleomorphism and abundant eosinophilic cytoplasm.
Leiomyosarcoma with myxoid matrix. Myxoid change in soft tissue leiomyosarcomas is unusual but may be seen.
Leiomyosarcoma. Leiomyosarcoma arising from the inferior vena cava.
Leiomyosarcoma. Low-grade leiomyosarcoma, composed of well-differentiated smooth muscle, with nuclear hyperchromatism and identifiable mitotic activity.
Leiomyosarcoma. Intermediate-grade leiomyosarcoma, arising from the wall of a vein. Many soft tissue leiomyosarcomas arise from vascular smooth muscle, and such tumours may be deceptively well circumscribed.
Leiomyosarcoma. Intermediate-grade leiomyosarcoma. The tumour cells show classic features of smooth muscle differentiation, with variably pleomorphic, elongated nuclei; perinuclear vacuoles; and distinctly eosinophilic cytoplasm.
Leiomyosarcoma. Low-grade leiomyosarcoma with granular cell change. Leiomyosarcomas with this unusual morphological feature may be confused with granular cell tumours.
Leiomyosarcoma. Dedifferentiated leiomyosarcoma, showing an abrupt transition from conventional grade 2 leiomyosarcoma to an essentially undifferentiated-appearing pleomorphic sarcoma. These undifferentiated areas lacked expression of muscle markers.
Leiomyosarcoma. Axial contrast-enhanced CT shows a right-sided retroperitoneal mass (solid arrow), which is clearly arising from the inferior vena cava. The lumen of the inferior vena cava is partially occluded (slit-like residual lumen indicated by dashed arrow).

Q: On T2-weighted MRI, an Intramuscular Myxoma classically presents as a well-circumscribed, markedly [...] mass due to its abundant myxoid stroma.
Intramuscular myxoma. T2-weighted MRI shows a well-circumscribed, hyperintense tumour.
A: hyperintense
Back Extra: Intramuscular Myxoma
- Clinical: Intramuscular myxoma presents as a slow-growing, painless mass, often bright on T2-weighted MRI.
- Micro: Characterized by bland spindle-shaped cells in an abundant myxoid stroma, with minimal vascularization and no necrosis.
- Ancillary: Immunohistochemistry shows positivity for CD34 and occasional presence of CD163-positive muciphages; GNAS mutation analysis can help differentiate from low-grade myxofibrosarcoma.
Reference Gallery:
Intramuscular myxoma. T2-weighted MRI shows a well-circumscribed, hyperintense tumour.
Intramuscular myxoma. Scanning magnification of an intramuscular myxoma.
Intramuscular myxoma. Intramuscular myxoma with entrapment of skeletal muscle fibres in the periphery.
Intramuscular myxoma. Intramuscular myxoma with extracellular matrix with frothy appearance, mimicking lipoblasts.
Intramuscular myxoma. Cellular intramuscular myxoma is a more cellular and more collagenous neoplasm, with bland uniform spindle cells lacking nuclear pleomorphism.
Mazabraud syndrome. Intramuscular myxomas are seen in the proximal muscles of the lower extremities (stars).
Mazabraud syndrome. Fibrous dysplasia is present in the proximal femur (arrow).
Intramuscular myxoma. Intramuscular myxoma composed of a gelatinous mass with internal septa. The tumour is well circumscribed overall but shows some infiltration of the surrounding skeletal muscle (left of tumour).

Q: Although composed of a well-circumscribed gelatinous mass, an Intramuscular Myxoma characteristically shows microscopic entrapment of [...] at its advancing periphery.
Intramuscular myxoma. Intramuscular myxoma with entrapment of skeletal muscle fibres in the periphery.
Intramuscular myxoma. Intramuscular myxoma composed of a gelatinous mass with internal septa. The tumour is well circumscribed overall but shows some infiltration of the surrounding skeletal muscle (left of tumour).
A: skeletal muscle fibers
Back Extra: Intramuscular Myxoma
- Clinical: Intramuscular myxoma presents as a slow-growing, painless mass, often bright on T2-weighted MRI.
- Micro: Characterized by bland spindle-shaped cells in an abundant myxoid stroma, with minimal vascularization and no necrosis.
- Ancillary: Immunohistochemistry shows positivity for CD34 and occasional presence of CD163-positive muciphages; GNAS mutation analysis can help differentiate from low-grade myxofibrosarcoma.
Reference Gallery:
Intramuscular myxoma. T2-weighted MRI shows a well-circumscribed, hyperintense tumour.
Intramuscular myxoma. Scanning magnification of an intramuscular myxoma.
Intramuscular myxoma. Intramuscular myxoma with entrapment of skeletal muscle fibres in the periphery.
Intramuscular myxoma. Intramuscular myxoma with extracellular matrix with frothy appearance, mimicking lipoblasts.
Intramuscular myxoma. Cellular intramuscular myxoma is a more cellular and more collagenous neoplasm, with bland uniform spindle cells lacking nuclear pleomorphism.
Mazabraud syndrome. Intramuscular myxomas are seen in the proximal muscles of the lower extremities (stars).
Mazabraud syndrome. Fibrous dysplasia is present in the proximal femur (arrow).
Intramuscular myxoma. Intramuscular myxoma composed of a gelatinous mass with internal septa. The tumour is well circumscribed overall but shows some infiltration of the surrounding skeletal muscle (left of tumour).

Q: The clinical presentation of an Intramuscular Myxoma (often multiple) associated with fibrous dysplasia of bone is diagnostic of [...].
Mazabraud syndrome. Intramuscular myxomas are seen in the proximal muscles of the lower extremities (stars).
Mazabraud syndrome. Fibrous dysplasia is present in the proximal femur (arrow).
A: Mazabraud syndrome
Back Extra: Intramuscular Myxoma
- Clinical: Intramuscular myxoma presents as a slow-growing, painless mass, often bright on T2-weighted MRI.
- Micro: Characterized by bland spindle-shaped cells in an abundant myxoid stroma, with minimal vascularization and no necrosis.
- Ancillary: Immunohistochemistry shows positivity for CD34 and occasional presence of CD163-positive muciphages; GNAS mutation analysis can help differentiate from low-grade myxofibrosarcoma.
Reference Gallery:
Intramuscular myxoma. T2-weighted MRI shows a well-circumscribed, hyperintense tumour.
Intramuscular myxoma. Scanning magnification of an intramuscular myxoma.
Intramuscular myxoma. Intramuscular myxoma with entrapment of skeletal muscle fibres in the periphery.
Intramuscular myxoma. Intramuscular myxoma with extracellular matrix with frothy appearance, mimicking lipoblasts.
Intramuscular myxoma. Cellular intramuscular myxoma is a more cellular and more collagenous neoplasm, with bland uniform spindle cells lacking nuclear pleomorphism.
Mazabraud syndrome. Intramuscular myxomas are seen in the proximal muscles of the lower extremities (stars).
Mazabraud syndrome. Fibrous dysplasia is present in the proximal femur (arrow).
Intramuscular myxoma. Intramuscular myxoma composed of a gelatinous mass with internal septa. The tumour is well circumscribed overall but shows some infiltration of the surrounding skeletal muscle (left of tumour).

Q: In Juxta-articular Myxoma, the tumor features bland spindle cells in a myxoid stroma and characteristically lacks the [...] mutations typically seen in intramuscular myxomas.
Juxta-articular myxoma. Myxoid stroma with bland spindle cells resembling areas of cellular myxoma.
A: GNAS
Back Extra: Juxta-articular Myxoma
- Clinical: Patients typically present with a swelling or mass near large joints, often associated with tenderness or pain.
- Micro: The tumour is hypocellular with bland spindle-shaped cells in a myxoid stroma, and may show increased cellularity and cystic spaces.
- Ancillary: Unlike intramuscular myxomas, juxta-articular myxomas do not demonstrate GNAS mutations.
Reference Gallery:
Juxta-articular myxoma. Cystic area filled with myxoid material surrounded by a more cellular proliferation.
Juxta-articular myxoma. Myxoid stroma with bland spindle cells resembling areas of cellular myxoma.
Juxta-articular myxoma. MRI of a tumour located adjacent to the knee joint, showing a homogeneous bright signal, similar to intramuscular myxoma.

Q: A key histologic feature of Juxta-articular Myxoma that often accompanies increased cellularity is the presence of [...] spaces within the myxoid material.
Juxta-articular myxoma. Cystic area filled with myxoid material surrounded by a more cellular proliferation.
A: cystic
Back Extra: Juxta-articular Myxoma
- Clinical: Patients typically present with a swelling or mass near large joints, often associated with tenderness or pain.
- Micro: The tumour is hypocellular with bland spindle-shaped cells in a myxoid stroma, and may show increased cellularity and cystic spaces.
- Ancillary: Unlike intramuscular myxomas, juxta-articular myxomas do not demonstrate GNAS mutations.
Reference Gallery:
Juxta-articular myxoma. Cystic area filled with myxoid material surrounded by a more cellular proliferation.
Juxta-articular myxoma. Myxoid stroma with bland spindle cells resembling areas of cellular myxoma.
Juxta-articular myxoma. MRI of a tumour located adjacent to the knee joint, showing a homogeneous bright signal, similar to intramuscular myxoma.

Q: On MRI, Juxta-articular Myxoma typically presents as a homogeneous bright-signal tumor near a large joint, closely mimicking the imaging appearance of a(n) [...].
Juxta-articular myxoma. MRI of a tumour located adjacent to the knee joint, showing a homogeneous bright signal, similar to intramuscular myxoma.
A: intramuscular myxoma
Back Extra: Juxta-articular Myxoma
- Clinical: Patients typically present with a swelling or mass near large joints, often associated with tenderness or pain.
- Micro: The tumour is hypocellular with bland spindle-shaped cells in a myxoid stroma, and may show increased cellularity and cystic spaces.
- Ancillary: Unlike intramuscular myxomas, juxta-articular myxomas do not demonstrate GNAS mutations.
Reference Gallery:
Juxta-articular myxoma. Cystic area filled with myxoid material surrounded by a more cellular proliferation.
Juxta-articular myxoma. Myxoid stroma with bland spindle cells resembling areas of cellular myxoma.
Juxta-articular myxoma. MRI of a tumour located adjacent to the knee joint, showing a homogeneous bright signal, similar to intramuscular myxoma.

Q: Radiographically and clinically, a Soft Tissue Chondroma typically presents as a slowly enlarging, mineralized mass that is characteristically completely separate from the underlying [...].
Soft tissue chondroma. Small oval mineralized mass in soft tissues separate from the phalange.
A: bone
Back Extra: Soft Tissue Chondroma
- Clinical: Soft tissue chondromas are typically solitary, painless, firm, and slowly enlarging masses that are well demarcated from bone and have spiculated or ring-like calcifications on imaging.
- Micro: The histology shows well-formed hyaline or myxoid cartilage with chondrocytes in lacunae, often with mild to moderate pleomorphism and coarse calcifications.
- Ancillary: Cytogenetic studies may reveal rearrangements of 12q13-q15 and trisomy 5, with about 50% of cases showing FN1 gene rearrangements.
Reference Gallery:
Soft tissue chondroma. Small oval mineralized mass in soft tissues separate from the phalange.
Soft tissue chondroma. Mass is well circumscribed by fibrous pseudocapsule.
Soft tissue chondroma. Chondrocytes in lacunae and surrounded by abundant well-formed hyaline matrix.
Soft tissue chondroma. Cellular tumour with chondrocytes that have mildly enlarged nuclei.
Soft tissue chondroma. Chondroblastoma-like soft tissue chondroma is cellular, the chondrocytes are large, and the matrix contains calcification around individual cells.

Q: Histologically, a Soft Tissue Chondroma is frequently demarcated by a fibrous pseudocapsule and is composed of chondrocytes residing in distinct lacunae surrounded by abundant, well-formed [...] or myxoid matrix.
Soft tissue chondroma. Mass is well circumscribed by fibrous pseudocapsule.
Soft tissue chondroma. Chondrocytes in lacunae and surrounded by abundant well-formed hyaline matrix.
A: hyaline
Back Extra: Soft Tissue Chondroma
- Clinical: Soft tissue chondromas are typically solitary, painless, firm, and slowly enlarging masses that are well demarcated from bone and have spiculated or ring-like calcifications on imaging.
- Micro: The histology shows well-formed hyaline or myxoid cartilage with chondrocytes in lacunae, often with mild to moderate pleomorphism and coarse calcifications.
- Ancillary: Cytogenetic studies may reveal rearrangements of 12q13-q15 and trisomy 5, with about 50% of cases showing FN1 gene rearrangements.
Reference Gallery:
Soft tissue chondroma. Small oval mineralized mass in soft tissues separate from the phalange.
Soft tissue chondroma. Mass is well circumscribed by fibrous pseudocapsule.
Soft tissue chondroma. Chondrocytes in lacunae and surrounded by abundant well-formed hyaline matrix.
Soft tissue chondroma. Cellular tumour with chondrocytes that have mildly enlarged nuclei.
Soft tissue chondroma. Chondroblastoma-like soft tissue chondroma is cellular, the chondrocytes are large, and the matrix contains calcification around individual cells.

Q: The [...] variant of a Soft Tissue Chondroma is a highly cellular tumor that features enlarged chondrocytes and characteristic matrix calcifications surrounding individual cells.
Soft tissue chondroma. Cellular tumour with chondrocytes that have mildly enlarged nuclei.
Soft tissue chondroma. Chondroblastoma-like soft tissue chondroma is cellular, the chondrocytes are large, and the matrix contains calcification around individual cells.
A: chondroblastoma-like
Back Extra: Soft Tissue Chondroma
- Clinical: Soft tissue chondromas are typically solitary, painless, firm, and slowly enlarging masses that are well demarcated from bone and have spiculated or ring-like calcifications on imaging.
- Micro: The histology shows well-formed hyaline or myxoid cartilage with chondrocytes in lacunae, often with mild to moderate pleomorphism and coarse calcifications.
- Ancillary: Cytogenetic studies may reveal rearrangements of 12q13-q15 and trisomy 5, with about 50% of cases showing FN1 gene rearrangements.
Reference Gallery:
Soft tissue chondroma. Small oval mineralized mass in soft tissues separate from the phalange.
Soft tissue chondroma. Mass is well circumscribed by fibrous pseudocapsule.
Soft tissue chondroma. Chondrocytes in lacunae and surrounded by abundant well-formed hyaline matrix.
Soft tissue chondroma. Cellular tumour with chondrocytes that have mildly enlarged nuclei.
Soft tissue chondroma. Chondroblastoma-like soft tissue chondroma is cellular, the chondrocytes are large, and the matrix contains calcification around individual cells.

Q: Morphologically, PEComa typically exhibits a nested architecture composed of epithelioid cells with abundant [...] cytoplasm.
PEComa. Note the typical nested architecture.
PEComa. The epithelioid tumour cells contain abundant clear cytoplasm.
A: clear to granular eosinophilic
Back Extra: PEComa
- Clinical: PEComas of soft tissue usually present as painless masses, more frequent in females, and are rarely associated with tuberous sclerosis.
- Micro: PEComas show a nested architecture with epithelioid cells having abundant granular eosinophilic or clear cytoplasm, and a perivascular growth pattern.
- Ancillary: PEComas characteristically express both melanocytic markers (HMB45, melan-A) and muscle markers (SMA, desmin), and approximately 15% show nuclear TFE3 expression due to TFE3 rearrangement.
Reference Gallery:
PEComa with TFE3 rearrangement. PEComa with TFE3 rearrangement showing nested and solid alveolar growth patterns and epithelioid tumour cells with moderate amounts of granular eosinophilic cytoplasm.
PEComa with TFE3 rearrangement. Nuclear TFE3 expression in PEComa corresponding to the presence of TFE3 rearrangement.
PEComa. This pancreatic tumour is grossly well circumscribed, with a fleshy cut surface.
PEComa. Note the typical nested architecture.
PEComa. The epithelioid tumour cells contain abundant clear cytoplasm.
Sclerosing PEComa. The tumour cells are focally situated within the wall of a dilated blood vessel.
PEComa. This tumour is composed of small nests of clear cells with small round nuclei and sharply defined cell borders (sugar tumour).
PEComa. A tumour with a sheet-like growth pattern. Note the granular to clear cytoplasm and uniform nuclear morphology.
PEComa. Loss of chromosome arm 16p demonstrated by comparative genomic hybridization and loss-of-heterozygosity analysis using microsatellite markers Sm7 and D16S521 (arrows), which flank the locus of the TSC2 gene.
PEComa. Some tumours show spindle cell morphology.
PEComa. Malignant PEComa composed of epithelioid tumour cells with clear cytoplasm, nuclear atypia, and mitotic activity. Note the trabecular architecture.
PEComa. A malignant PEComa with marked nuclear atypia and pleomorphism. Note the abundant granular eosinophilic cytoplasm.

Q: A subset of PEComa tumors harbor a specific gene rearrangement that results in characteristic nuclear immunohistochemical expression of [...].
PEComa with TFE3 rearrangement. PEComa with TFE3 rearrangement showing nested and solid alveolar growth patterns and epithelioid tumour cells with moderate amounts of granular eosinophilic cytoplasm.
PEComa with TFE3 rearrangement. Nuclear TFE3 expression in PEComa corresponding to the presence of TFE3 rearrangement.
A: TFE3
Back Extra: PEComa
- Clinical: PEComas of soft tissue usually present as painless masses, more frequent in females, and are rarely associated with tuberous sclerosis.
- Micro: PEComas show a nested architecture with epithelioid cells having abundant granular eosinophilic or clear cytoplasm, and a perivascular growth pattern.
- Ancillary: PEComas characteristically express both melanocytic markers (HMB45, melan-A) and muscle markers (SMA, desmin), and approximately 15% show nuclear TFE3 expression due to TFE3 rearrangement.
Reference Gallery:
PEComa with TFE3 rearrangement. PEComa with TFE3 rearrangement showing nested and solid alveolar growth patterns and epithelioid tumour cells with moderate amounts of granular eosinophilic cytoplasm.
PEComa with TFE3 rearrangement. Nuclear TFE3 expression in PEComa corresponding to the presence of TFE3 rearrangement.
PEComa. This pancreatic tumour is grossly well circumscribed, with a fleshy cut surface.
PEComa. Note the typical nested architecture.
PEComa. The epithelioid tumour cells contain abundant clear cytoplasm.
Sclerosing PEComa. The tumour cells are focally situated within the wall of a dilated blood vessel.
PEComa. This tumour is composed of small nests of clear cells with small round nuclei and sharply defined cell borders (sugar tumour).
PEComa. A tumour with a sheet-like growth pattern. Note the granular to clear cytoplasm and uniform nuclear morphology.
PEComa. Loss of chromosome arm 16p demonstrated by comparative genomic hybridization and loss-of-heterozygosity analysis using microsatellite markers Sm7 and D16S521 (arrows), which flank the locus of the TSC2 gene.
PEComa. Some tumours show spindle cell morphology.
PEComa. Malignant PEComa composed of epithelioid tumour cells with clear cytoplasm, nuclear atypia, and mitotic activity. Note the trabecular architecture.
PEComa. A malignant PEComa with marked nuclear atypia and pleomorphism. Note the abundant granular eosinophilic cytoplasm.

Q: The pathogenesis of PEComa often involves loss-of-heterozygosity at chromosome 16p, disrupting the locus for the [...] gene and linking the tumor to tuberous sclerosis.
PEComa. Loss of chromosome arm 16p demonstrated by comparative genomic hybridization and loss-of-heterozygosity analysis using microsatellite markers Sm7 and D16S521 (arrows), which flank the locus of the TSC2 gene.
A: TSC2
Back Extra: PEComa
- Clinical: PEComas of soft tissue usually present as painless masses, more frequent in females, and are rarely associated with tuberous sclerosis.
- Micro: PEComas show a nested architecture with epithelioid cells having abundant granular eosinophilic or clear cytoplasm, and a perivascular growth pattern.
- Ancillary: PEComas characteristically express both melanocytic markers (HMB45, melan-A) and muscle markers (SMA, desmin), and approximately 15% show nuclear TFE3 expression due to TFE3 rearrangement.
Reference Gallery:
PEComa with TFE3 rearrangement. PEComa with TFE3 rearrangement showing nested and solid alveolar growth patterns and epithelioid tumour cells with moderate amounts of granular eosinophilic cytoplasm.
PEComa with TFE3 rearrangement. Nuclear TFE3 expression in PEComa corresponding to the presence of TFE3 rearrangement.
PEComa. This pancreatic tumour is grossly well circumscribed, with a fleshy cut surface.
PEComa. Note the typical nested architecture.
PEComa. The epithelioid tumour cells contain abundant clear cytoplasm.
Sclerosing PEComa. The tumour cells are focally situated within the wall of a dilated blood vessel.
PEComa. This tumour is composed of small nests of clear cells with small round nuclei and sharply defined cell borders (sugar tumour).
PEComa. A tumour with a sheet-like growth pattern. Note the granular to clear cytoplasm and uniform nuclear morphology.
PEComa. Loss of chromosome arm 16p demonstrated by comparative genomic hybridization and loss-of-heterozygosity analysis using microsatellite markers Sm7 and D16S521 (arrows), which flank the locus of the TSC2 gene.
PEComa. Some tumours show spindle cell morphology.
PEComa. Malignant PEComa composed of epithelioid tumour cells with clear cytoplasm, nuclear atypia, and mitotic activity. Note the trabecular architecture.
PEComa. A malignant PEComa with marked nuclear atypia and pleomorphism. Note the abundant granular eosinophilic cytoplasm.

Q: Histologically, Deep (aggressive) angiomyxoma is a paucicellular tumor featuring bland spindle cells set within an abundant myxoid matrix, interspersed with medium-to-large vessels that are characteristically surrounded by [...].
Deep (aggressive) angiomyxoma. The spindle-shaped cells have delicate cytoplasmic processes and ovoid bland nuclei. The myoid bundles are typically arranged in loose clusters or tight whorls around the vascular component.
Deep (aggressive) angiomyxoma. Medium-sized to large vessels can be seen, with thickened walls. Note the presence of particularly distinct myoid bundles wrapping about vessels of various calibres.
A: myoid bundles
Back Extra: Deep (aggressive) angiomyxoma
- Clinical: Deep (aggressive) angiomyxoma typically presents as a slow-growing, deep-seated painless mass in the pelviperineal region. MRI may reveal a laminated appearance (swirl sign).
- Micro: Histologically, the tumour is composed of bland spindle cells in a myxoid matrix with prominent medium to large vessels and myoid bundles arranged around the vessels.
- Ancillary: Immunohistochemically, spindle cells are positive for desmin, CD34, and SMA (mainly in myoid bundles). HMGA2 is a sensitive marker for deep (aggressive) angiomyxoma, and molecular studies often show HMGA2 rearrangements.
Reference Gallery:
Deep (aggressive) angiomyxoma. The spindle-shaped cells have delicate cytoplasmic processes and ovoid bland nuclei. The myoid bundles are typically arranged in loose clusters or tight whorls around the vascular component.
Deep (aggressive) angiomyxoma. When present, aberrant HMGA2 expression is a useful diagnostic marker for deep (aggressive) angiomyxoma. It is particularly helpful in defining the margin of the tumour, because non-neoplastic mesenchyme lacks expression.
Deep (aggressive) angiomyxoma. HMGA2 (12q14.3) rearrangement. A Partial G-banded karyotype exhibiting a t(12;21)(q15;q21.1) in an aggressive angiomyxoma. B,C Dual-colour FISH with a probe set flanking HMGA2 demonstrates the presence of a rearrangement of this locus in tumour interphase nuclei (split red and green signals).
Deep (aggressive) angiomyxoma. This tumour is characteristically paucicellular and composed of bland spindle cells set within an abundant myxoid matrix interspersed with prominent vessels.
Deep (aggressive) angiomyxoma. Medium-sized to large vessels can be seen, with thickened walls. Note the presence of particularly distinct myoid bundles wrapping about vessels of various calibres.
Deep (aggressive) angiomyxoma. This tumour is characteristically paucicellular and composed of bland spindle cells set within an abundant myxoid matrix interspersed with medium-sized to large vessels.

Q: When evaluating the margins of a suspected Deep (aggressive) angiomyxoma, aberrant nuclear expression of [...] is a highly sensitive diagnostic marker due to frequent translocations involving its gene locus at 12q14.3.
Deep (aggressive) angiomyxoma. When present, aberrant HMGA2 expression is a useful diagnostic marker for deep (aggressive) angiomyxoma. It is particularly helpful in defining the margin of the tumour, because non-neoplastic mesenchyme lacks expression.
Deep (aggressive) angiomyxoma. HMGA2 (12q14.3) rearrangement. A Partial G-banded karyotype exhibiting a t(12;21)(q15;q21.1) in an aggressive angiomyxoma. B,C Dual-colour FISH with a probe set flanking HMGA2 demonstrates the presence of a rearrangement of this locus in tumour interphase nuclei (split red and green signals).
A: HMGA2
Back Extra: Deep (aggressive) angiomyxoma
- Clinical: Deep (aggressive) angiomyxoma typically presents as a slow-growing, deep-seated painless mass in the pelviperineal region. MRI may reveal a laminated appearance (swirl sign).
- Micro: Histologically, the tumour is composed of bland spindle cells in a myxoid matrix with prominent medium to large vessels and myoid bundles arranged around the vessels.
- Ancillary: Immunohistochemically, spindle cells are positive for desmin, CD34, and SMA (mainly in myoid bundles). HMGA2 is a sensitive marker for deep (aggressive) angiomyxoma, and molecular studies often show HMGA2 rearrangements.
Reference Gallery:
Deep (aggressive) angiomyxoma. The spindle-shaped cells have delicate cytoplasmic processes and ovoid bland nuclei. The myoid bundles are typically arranged in loose clusters or tight whorls around the vascular component.
Deep (aggressive) angiomyxoma. When present, aberrant HMGA2 expression is a useful diagnostic marker for deep (aggressive) angiomyxoma. It is particularly helpful in defining the margin of the tumour, because non-neoplastic mesenchyme lacks expression.
Deep (aggressive) angiomyxoma. HMGA2 (12q14.3) rearrangement. A Partial G-banded karyotype exhibiting a t(12;21)(q15;q21.1) in an aggressive angiomyxoma. B,C Dual-colour FISH with a probe set flanking HMGA2 demonstrates the presence of a rearrangement of this locus in tumour interphase nuclei (split red and green signals).
Deep (aggressive) angiomyxoma. This tumour is characteristically paucicellular and composed of bland spindle cells set within an abundant myxoid matrix interspersed with prominent vessels.
Deep (aggressive) angiomyxoma. Medium-sized to large vessels can be seen, with thickened walls. Note the presence of particularly distinct myoid bundles wrapping about vessels of various calibres.
Deep (aggressive) angiomyxoma. This tumour is characteristically paucicellular and composed of bland spindle cells set within an abundant myxoid matrix interspersed with medium-sized to large vessels.

Q: Microscopically, [...] displays a wide morphologic spectrum, characteristically forming reticular, trabecular, and solid patterns within a myxoid stroma, composed of variably spindle, epithelioid, and plasmacytoid cells.
Myoepithelial tumour of soft tissue. Lobulated growth with reticular and trabecular patterns and myxoid stroma.
Myoepithelial tumour of soft tissue. Epithelioid and spindle cells with eosinophilic cytoplasm arranged in trabeculae.
Myoepithelioma. Bland-appearing ovoid and epithelioid cells with uniform nuclei and eosinophilic cytoplasm.
A: myoepithelioma, myoepithelial carcinoma, and mixed tumor
Q: Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour
- Clinical: Most patients with [...] present with a painless, palpable mass, often in the limbs and limb girdles.
- Micro: [...] show a wide morphological spectrum, including reticular, trabecular, and solid patterns, with myxoid stroma and variably spindle, epithelioid, and plasmacytoid cells.
- Ancillary: Immunohistochemistry for [...] typically shows positivity for broad-spectrum keratins, S100, and often EMA, SOX10, and calponin.
Reference Gallery:
Myoepithelial tumour of soft tissue. Lobulated growth with reticular and trabecular patterns and myxoid stroma.
Myoepithelial tumour of soft tissue. Epithelioid and spindle cells with eosinophilic cytoplasm arranged in trabeculae.
Myoepithelioma. Bland-appearing ovoid and epithelioid cells with uniform nuclei and eosinophilic cytoplasm.
Myoepithelioma. Tumour cells may show clear cell change.
Myoepithelioma. Cartilaginous and/or osseous differentiation is seen in about 10% of cases.
Mixed tumour of soft tissue. Tumours show ductal differentiation and are indistinguishable from salivary pleomorphic adenoma.
Myoepithelial carcinoma. Nuclei show appreciable atypia and readily identifiable nucleoli.
Myoepithelioma. Most cases show strong keratin immunoreactivity (CAM5.2 shown here).
Myoepithelioma. S100 is positive in most cases.
A: Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour; Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour; Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour

Q: Immunohistochemistry for myoepithelioma, myoepithelial carcinoma, and mixed tumor is typically positive for broad-spectrum keratins (e.g., CAM5.2) and [...], often along with EMA, SOX10, and calponin.
Myoepithelioma. Most cases show strong keratin immunoreactivity (CAM5.2 shown here).
Myoepithelioma. S100 is positive in most cases.
A: S100
Q: Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour
- Clinical: Most patients with [...] present with a painless, palpable mass, often in the limbs and limb girdles.
- Micro: [...] show a wide morphological spectrum, including reticular, trabecular, and solid patterns, with myxoid stroma and variably spindle, epithelioid, and plasmacytoid cells.
- Ancillary: Immunohistochemistry for [...] typically shows positivity for broad-spectrum keratins, S100, and often EMA, SOX10, and calponin.
Reference Gallery:
Myoepithelial tumour of soft tissue. Lobulated growth with reticular and trabecular patterns and myxoid stroma.
Myoepithelial tumour of soft tissue. Epithelioid and spindle cells with eosinophilic cytoplasm arranged in trabeculae.
Myoepithelioma. Bland-appearing ovoid and epithelioid cells with uniform nuclei and eosinophilic cytoplasm.
Myoepithelioma. Tumour cells may show clear cell change.
Myoepithelioma. Cartilaginous and/or osseous differentiation is seen in about 10% of cases.
Mixed tumour of soft tissue. Tumours show ductal differentiation and are indistinguishable from salivary pleomorphic adenoma.
Myoepithelial carcinoma. Nuclei show appreciable atypia and readily identifiable nucleoli.
Myoepithelioma. Most cases show strong keratin immunoreactivity (CAM5.2 shown here).
Myoepithelioma. S100 is positive in most cases.
A: Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour; Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour; Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour

Q: Within the spectrum of myoepithelioma, myoepithelial carcinoma, and mixed tumor, the mixed tumor variant is morphologically defined by the presence of [...], making it indistinguishable from a salivary pleomorphic adenoma.
Mixed tumour of soft tissue. Tumours show ductal differentiation and are indistinguishable from salivary pleomorphic adenoma.
A: ductal differentiation
Q: Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour
- Clinical: Most patients with [...] present with a painless, palpable mass, often in the limbs and limb girdles.
- Micro: [...] show a wide morphological spectrum, including reticular, trabecular, and solid patterns, with myxoid stroma and variably spindle, epithelioid, and plasmacytoid cells.
- Ancillary: Immunohistochemistry for [...] typically shows positivity for broad-spectrum keratins, S100, and often EMA, SOX10, and calponin.
Reference Gallery:
Myoepithelial tumour of soft tissue. Lobulated growth with reticular and trabecular patterns and myxoid stroma.
Myoepithelial tumour of soft tissue. Epithelioid and spindle cells with eosinophilic cytoplasm arranged in trabeculae.
Myoepithelioma. Bland-appearing ovoid and epithelioid cells with uniform nuclei and eosinophilic cytoplasm.
Myoepithelioma. Tumour cells may show clear cell change.
Myoepithelioma. Cartilaginous and/or osseous differentiation is seen in about 10% of cases.
Mixed tumour of soft tissue. Tumours show ductal differentiation and are indistinguishable from salivary pleomorphic adenoma.
Myoepithelial carcinoma. Nuclei show appreciable atypia and readily identifiable nucleoli.
Myoepithelioma. Most cases show strong keratin immunoreactivity (CAM5.2 shown here).
Myoepithelioma. S100 is positive in most cases.
A: Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour; Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour; Myoepithelioma, Myoepithelial Carcinoma, and Mixed Tumour

Q: Histologically, an Ossifying Fibromyxoid Tumor is composed of cords and trabeculae of ovoid cells in a fibromyxoid matrix, and is classically surrounded by a [...].
Ossifying fibromyxoid tumour. Low magnification reveals a partial rim of metaplastic bone.
Ossifying fibromyxoid tumour. Trabecular architecture with focal cystic change.
Ossifying fibromyxoid tumour. The characteristic architectural and cytological features of ossifying fibromyxoid tumour. Note the varying trabecular and solid patterns, delicate nucleoli, and mitotic figures.
A: peripheral shell of metaplastic bone
Back Extra: Ossifying Fibromyxoid Tumour
- Clinical: Ossifying Fibromyxoid Tumour (OFMT) typically presents as a painless, slow-growing, elastic, hard mass, often in the subcutaneous tissue, with radiological features of a well-circumscribed, lobulated mass.
- Micro: OFMTs are characterized by cords and trabeculae of ovoid cells in a fibromyxoid matrix, often surrounded by a peripheral shell of metaplastic bone.
- Ancillary: PHF1 gene rearrangement is a key molecular feature of OFMT, with the most common fusion being EP400-PHF1.
Reference Gallery:
Ossifying fibromyxoid tumour. A well-demarcated tumour in the subcutis, whitish and translucent in gross appearance.
Ossifying fibromyxoid tumour. Low magnification reveals a partial rim of metaplastic bone.
Ossifying fibromyxoid tumour. Multinodular pattern.
Ossifying fibromyxoid tumour. Satellite nodules in the surrounding fat.
Ossifying fibromyxoid tumour. Trabecular architecture with focal cystic change.
Ossifying fibromyxoid tumour. The characteristic architectural and cytological features of ossifying fibromyxoid tumour. Note the varying trabecular and solid patterns, delicate nucleoli, and mitotic figures.
Ossifying fibromyxoid tumour. The characteristic architectural and cytological features of ossifying fibromyxoid tumour. Note the varying trabecular and solid patterns, delicate nucleoli, and mitotic figures.
Ossifying fibromyxoid tumour. The characteristic architectural and cytological features of ossifying fibromyxoid tumour. Note the varying trabecular and solid patterns, delicate nucleoli, and mitotic figures.
Ossifying fibromyxoid tumour. These tumours typically show both nuclear and cytoplasmic immunopositivity for S100.
Ossifying fibromyxoid tumour. CD10 immunoreactivity.

Q: In addition to its classic morphological features, the neoplastic cells of an Ossifying Fibromyxoid Tumor characteristically demonstrate both nuclear and cytoplasmic immunohistochemical positivity for [...].
Ossifying fibromyxoid tumour. These tumours typically show both nuclear and cytoplasmic immunopositivity for S100.
A: S100
Back Extra: Ossifying Fibromyxoid Tumour
- Clinical: Ossifying Fibromyxoid Tumour (OFMT) typically presents as a painless, slow-growing, elastic, hard mass, often in the subcutaneous tissue, with radiological features of a well-circumscribed, lobulated mass.
- Micro: OFMTs are characterized by cords and trabeculae of ovoid cells in a fibromyxoid matrix, often surrounded by a peripheral shell of metaplastic bone.
- Ancillary: PHF1 gene rearrangement is a key molecular feature of OFMT, with the most common fusion being EP400-PHF1.
Reference Gallery:
Ossifying fibromyxoid tumour. A well-demarcated tumour in the subcutis, whitish and translucent in gross appearance.
Ossifying fibromyxoid tumour. Low magnification reveals a partial rim of metaplastic bone.
Ossifying fibromyxoid tumour. Multinodular pattern.
Ossifying fibromyxoid tumour. Satellite nodules in the surrounding fat.
Ossifying fibromyxoid tumour. Trabecular architecture with focal cystic change.
Ossifying fibromyxoid tumour. The characteristic architectural and cytological features of ossifying fibromyxoid tumour. Note the varying trabecular and solid patterns, delicate nucleoli, and mitotic figures.
Ossifying fibromyxoid tumour. The characteristic architectural and cytological features of ossifying fibromyxoid tumour. Note the varying trabecular and solid patterns, delicate nucleoli, and mitotic figures.
Ossifying fibromyxoid tumour. The characteristic architectural and cytological features of ossifying fibromyxoid tumour. Note the varying trabecular and solid patterns, delicate nucleoli, and mitotic figures.
Ossifying fibromyxoid tumour. These tumours typically show both nuclear and cytoplasmic immunopositivity for S100.
Ossifying fibromyxoid tumour. CD10 immunoreactivity.

Q: A hallmark histological feature of Phosphaturic Mesenchymal Tumor is the presence of bland spindle to stellate cells embedded in a smudgy matrix with distinct [...].
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumours usually present as spindle cell tumours with focal grungy calcification.
Phosphaturic mesenchymal tumour. Tumours may be composed largely of basophilic matrix.
A: grungy calcification
Back Extra: Phosphaturic Mesenchymal Tumour
- Clinical: Phosphaturic mesenchymal tumours (PMTs) most commonly affect middle-aged adults and typically present with osteomalacia and severe hypophosphataemia due to overproduction of FGF23.
- Micro: PMTs are characterized by bland spindle to stellate cells with a hyalinized to smudgy-appearing matrix, grungy calcification, and a rich vascular network.
- Ancillary: Detection of FN1-FGFR1 or FN1-FGF1 fusions is confirmatory for PMTs, and most tumours express CD56, ERG, FGFR1, SATB2, and/or SSTR2A.
Reference Gallery:
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumours usually present as spindle cell tumours with focal grungy calcification.
Phosphaturic mesenchymal tumour. Bland spindle cells and a rich vascular network.
Phosphaturic mesenchymal tumour. Tumours may be composed largely of basophilic matrix.
Phosphaturic mesenchymal tumour. Adipocytic component and staghorn vessels.
Phosphaturic mesenchymal tumour. Areas rich in osteoclastic giant cells may resemble giant cell tumour of bone or soft tissue.
Phosphaturic mesenchymal tumour. Osteoblastoma-like phosphaturic mesenchymal tumour with prominent osteoid deposition.
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumour with chondroid matrix and nuclear atypia, mimicking chondrosarcoma.
Malignant phosphaturic mesenchymal tumour with fibrosarcoma-like pattern. Legend text not found

Q: In addition to bland spindle cells, Phosphaturic Mesenchymal Tumor often features a rich vascular network containing prominent [...] vessels, sometimes admixed with an adipocytic component.
Phosphaturic mesenchymal tumour. Adipocytic component and staghorn vessels.
A: staghorn
Back Extra: Phosphaturic Mesenchymal Tumour
- Clinical: Phosphaturic mesenchymal tumours (PMTs) most commonly affect middle-aged adults and typically present with osteomalacia and severe hypophosphataemia due to overproduction of FGF23.
- Micro: PMTs are characterized by bland spindle to stellate cells with a hyalinized to smudgy-appearing matrix, grungy calcification, and a rich vascular network.
- Ancillary: Detection of FN1-FGFR1 or FN1-FGF1 fusions is confirmatory for PMTs, and most tumours express CD56, ERG, FGFR1, SATB2, and/or SSTR2A.
Reference Gallery:
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumours usually present as spindle cell tumours with focal grungy calcification.
Phosphaturic mesenchymal tumour. Bland spindle cells and a rich vascular network.
Phosphaturic mesenchymal tumour. Tumours may be composed largely of basophilic matrix.
Phosphaturic mesenchymal tumour. Adipocytic component and staghorn vessels.
Phosphaturic mesenchymal tumour. Areas rich in osteoclastic giant cells may resemble giant cell tumour of bone or soft tissue.
Phosphaturic mesenchymal tumour. Osteoblastoma-like phosphaturic mesenchymal tumour with prominent osteoid deposition.
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumour with chondroid matrix and nuclear atypia, mimicking chondrosarcoma.
Malignant phosphaturic mesenchymal tumour with fibrosarcoma-like pattern. Legend text not found

Q: A diagnosis of [...] should be strongly suspected in a patient with severe hypophosphatemia when histopathology shows bland spindle cells, grungy calcification, and variably prominent osteoclast-like giant cells.
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumours usually present as spindle cell tumours with focal grungy calcification.
Phosphaturic mesenchymal tumour. Areas rich in osteoclastic giant cells may resemble giant cell tumour of bone or soft tissue.
A: Phosphaturic Mesenchymal Tumor
Back Extra: Phosphaturic Mesenchymal Tumour
- Clinical: Phosphaturic mesenchymal tumours (PMTs) most commonly affect middle-aged adults and typically present with osteomalacia and severe hypophosphataemia due to overproduction of FGF23.
- Micro: PMTs are characterized by bland spindle to stellate cells with a hyalinized to smudgy-appearing matrix, grungy calcification, and a rich vascular network.
- Ancillary: Detection of FN1-FGFR1 or FN1-FGF1 fusions is confirmatory for PMTs, and most tumours express CD56, ERG, FGFR1, SATB2, and/or SSTR2A.
Reference Gallery:
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumours usually present as spindle cell tumours with focal grungy calcification.
Phosphaturic mesenchymal tumour. Bland spindle cells and a rich vascular network.
Phosphaturic mesenchymal tumour. Tumours may be composed largely of basophilic matrix.
Phosphaturic mesenchymal tumour. Adipocytic component and staghorn vessels.
Phosphaturic mesenchymal tumour. Areas rich in osteoclastic giant cells may resemble giant cell tumour of bone or soft tissue.
Phosphaturic mesenchymal tumour. Osteoblastoma-like phosphaturic mesenchymal tumour with prominent osteoid deposition.
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumour with chondroid matrix and nuclear atypia, mimicking chondrosarcoma.
Malignant phosphaturic mesenchymal tumour with fibrosarcoma-like pattern. Legend text not found

Q: The soft tissue neoplasm characterized microscopically by clusters of ectatic, thin-walled blood vessels with a thick rim of amorphous, eosinophilic material and a stroma containing pleomorphic, hemosiderin-laden cells is [...].
Classic pleomorphic hyalinizing angiectatic tumour. Classic pleomorphic hyalinizing angiectatic tumour shows ectatic thin-walled vessels lined by fibrin-like hyaline material surrounded by paucicellular stroma containing spindled cells with variable nuclear pleomorphism.
Pleomorphic hyalinizing angiectatic tumour. Pleomorphic hyalinizing angiectatic tumour contains increased numbers of atypical stromal cells with lobulated large nuclei and prominent nucleoli.
A: pleomorphic hyalinizing angiectatic tumor of soft parts
Back Extra: Pleomorphic Hyalinizing Angiectatic Tumour of Soft Parts
- Clinical: Pleomorphic hyalinizing angiectatic tumour (PHAT) most often presents as a longstanding subcutaneous mass, commonly mimicking vascular tumours like haemangioma or Kaposi sarcoma.
- Micro: Microscopically, PHAT is characterized by clusters of ectatic, thin-walled blood vessels surrounded by a thick rim of amorphous eosinophilic material, with pleomorphic, haemosiderin-laden cells and a low mitotic rate.
- Ancillary: Some PHATs show rearrangements involving TGFBR3 and/or OGA (MGEA5), which can be detected by FISH.
Reference Gallery:
Classic pleomorphic hyalinizing angiectatic tumour. Classic pleomorphic hyalinizing angiectatic tumour shows ectatic thin-walled vessels lined by fibrin-like hyaline material surrounded by paucicellular stroma containing spindled cells with variable nuclear pleomorphism.
Pleomorphic hyalinizing angiectatic tumour. Pleomorphic hyalinizing angiectatic tumour contains increased numbers of atypical stromal cells with lobulated large nuclei and prominent nucleoli.
Early pleomorphic hyalinizing angiectatic tumour. An example showing both haemosiderotic fibrolipomatous tumour–like features (left) and classic pleomorphic hyalinizing angiectatic tumour with increased cellularity and ectatic blood vessels (right).
Classic pleomorphic hyalinizing angiectatic tumour. A dispersed mononuclear inflammatory component may be seen in the background stroma of pleomorphic hyalinizing angiectatic tumour.
Classic pleomorphic hyalinizing angiectatic tumour with OGA (MGEA5) gene fusion. Haemosiderotic changes are seen in the stromal cells.
OGA (MGEA5) FISH in pleomorphic hyalinizing angiectatic tumour. A subset of pleomorphic hyalinizing angiectatic tumours harbour OGA (MGEA5) gene fusions, as illustrated here by break-apart signals of the OGA (MGEA5) gene locus.

Q: Ancillary FISH testing in pleomorphic hyalinizing angiectatic tumor of soft parts may reveal characteristic gene rearrangements involving TGFBR3 and/or [...].
OGA (MGEA5) FISH in pleomorphic hyalinizing angiectatic tumour. A subset of pleomorphic hyalinizing angiectatic tumours harbour OGA (MGEA5) gene fusions, as illustrated here by break-apart signals of the OGA (MGEA5) gene locus.
A: OGA (MGEA5)
Back Extra: Pleomorphic Hyalinizing Angiectatic Tumour of Soft Parts
- Clinical: Pleomorphic hyalinizing angiectatic tumour (PHAT) most often presents as a longstanding subcutaneous mass, commonly mimicking vascular tumours like haemangioma or Kaposi sarcoma.
- Micro: Microscopically, PHAT is characterized by clusters of ectatic, thin-walled blood vessels surrounded by a thick rim of amorphous eosinophilic material, with pleomorphic, haemosiderin-laden cells and a low mitotic rate.
- Ancillary: Some PHATs show rearrangements involving TGFBR3 and/or OGA (MGEA5), which can be detected by FISH.
Reference Gallery:
Classic pleomorphic hyalinizing angiectatic tumour. Classic pleomorphic hyalinizing angiectatic tumour shows ectatic thin-walled vessels lined by fibrin-like hyaline material surrounded by paucicellular stroma containing spindled cells with variable nuclear pleomorphism.
Pleomorphic hyalinizing angiectatic tumour. Pleomorphic hyalinizing angiectatic tumour contains increased numbers of atypical stromal cells with lobulated large nuclei and prominent nucleoli.
Early pleomorphic hyalinizing angiectatic tumour. An example showing both haemosiderotic fibrolipomatous tumour–like features (left) and classic pleomorphic hyalinizing angiectatic tumour with increased cellularity and ectatic blood vessels (right).
Classic pleomorphic hyalinizing angiectatic tumour. A dispersed mononuclear inflammatory component may be seen in the background stroma of pleomorphic hyalinizing angiectatic tumour.
Classic pleomorphic hyalinizing angiectatic tumour with OGA (MGEA5) gene fusion. Haemosiderotic changes are seen in the stromal cells.
OGA (MGEA5) FISH in pleomorphic hyalinizing angiectatic tumour. A subset of pleomorphic hyalinizing angiectatic tumours harbour OGA (MGEA5) gene fusions, as illustrated here by break-apart signals of the OGA (MGEA5) gene locus.

Q: Early lesions of pleomorphic hyalinizing angiectatic tumor of soft parts often demonstrate a stroma laden with iron pigment and atypical spindled cells, showing significant histologic overlap with [...].
Early pleomorphic hyalinizing angiectatic tumour. An example showing both haemosiderotic fibrolipomatous tumour–like features (left) and classic pleomorphic hyalinizing angiectatic tumour with increased cellularity and ectatic blood vessels (right).
Classic pleomorphic hyalinizing angiectatic tumour with OGA (MGEA5) gene fusion. Haemosiderotic changes are seen in the stromal cells.
A: hemosiderotic fibrolipomatous tumor
Back Extra: Pleomorphic Hyalinizing Angiectatic Tumour of Soft Parts
- Clinical: Pleomorphic hyalinizing angiectatic tumour (PHAT) most often presents as a longstanding subcutaneous mass, commonly mimicking vascular tumours like haemangioma or Kaposi sarcoma.
- Micro: Microscopically, PHAT is characterized by clusters of ectatic, thin-walled blood vessels surrounded by a thick rim of amorphous eosinophilic material, with pleomorphic, haemosiderin-laden cells and a low mitotic rate.
- Ancillary: Some PHATs show rearrangements involving TGFBR3 and/or OGA (MGEA5), which can be detected by FISH.
Reference Gallery:
Classic pleomorphic hyalinizing angiectatic tumour. Classic pleomorphic hyalinizing angiectatic tumour shows ectatic thin-walled vessels lined by fibrin-like hyaline material surrounded by paucicellular stroma containing spindled cells with variable nuclear pleomorphism.
Pleomorphic hyalinizing angiectatic tumour. Pleomorphic hyalinizing angiectatic tumour contains increased numbers of atypical stromal cells with lobulated large nuclei and prominent nucleoli.
Early pleomorphic hyalinizing angiectatic tumour. An example showing both haemosiderotic fibrolipomatous tumour–like features (left) and classic pleomorphic hyalinizing angiectatic tumour with increased cellularity and ectatic blood vessels (right).
Classic pleomorphic hyalinizing angiectatic tumour. A dispersed mononuclear inflammatory component may be seen in the background stroma of pleomorphic hyalinizing angiectatic tumour.
Classic pleomorphic hyalinizing angiectatic tumour with OGA (MGEA5) gene fusion. Haemosiderotic changes are seen in the stromal cells.
OGA (MGEA5) FISH in pleomorphic hyalinizing angiectatic tumour. A subset of pleomorphic hyalinizing angiectatic tumours harbour OGA (MGEA5) gene fusions, as illustrated here by break-apart signals of the OGA (MGEA5) gene locus.

Q: Microscopically, Alveolar Soft Part Sarcoma features large polygonal cells with eosinophilic granular cytoplasm arranged in uniform organoid nests with central discohesion, creating a characteristic [...] architecture.
Alveolar soft part sarcoma. Compact cell nests outlined by sinusoidal vessels.
Alveolar soft part sarcoma. Alveolar-like structures, discohesive cells, and central or eccentric nuclei with prominent nucleoli.
Alveolar soft part sarcoma. Typical organoid nests of eosinophilic tumour cells with abundant cytoplasm.
A: alveolar
Back Extra: Alveolar Soft Part Sarcoma
- Clinical: Alveolar Soft Part Sarcoma (ASPS) typically presents as a slow-growing painless mass, and can involve the lungs, liver, bone, and brain with metastasis often occurring ≥ 10 years after diagnosis.
- Micro: ASPS is characterized by large polygonal cells with eosinophilic granular cytoplasm, arranged in a uniform organoid or nest-like pattern, creating a distinct alveolar architecture.
- Ancillary: Diagnosis of ASPS is confirmed by the presence of the TFE3 rearrangement or ASPSCR1-TFE3 fusion transcript, which is highly specific and sensitive for this tumour.
Reference Gallery:
Alveolar soft part sarcoma. Tumour involving fibula and calf muscles of a 13-year-old girl; postcontrast T1-weighted MRI images reveal a solid tumour with lobulated margins displaying inhomogeneous intense enhancement and a central non-enhancing component. Axial view.
Alveolar soft part sarcoma. Tumour involving fibula and calf muscles of a 13-year-old girl; postcontrast T1-weighted MRI images reveal a solid tumour with lobulated margins displaying inhomogeneous intense enhancement and a central non-enhancing component. Coronal view.
Alveolar soft part sarcoma. Compact cell nests outlined by sinusoidal vessels.
Alveolar soft part sarcoma. Alveolar-like structures, discohesive cells, and central or eccentric nuclei with prominent nucleoli.
Alveolar soft part sarcoma. Partial karyotype of alveolar soft part sarcoma showing the characteristic alteration, der(17)t(X;17)(p11.2;q25).
Alveolar soft part sarcoma. CD34 immunohistochemistry highlights the delicate capillaries surrounding the pseudoalveolar structures.
Alveolar soft part sarcoma. Nuclear staining with TFE3 is characteristic.
Alveolar soft part sarcoma. PASD staining. A large centrally placed cell shows elongated rod-like intracytoplasmic crystals in a sheaf-like arrangement; numerous surrounding cells show intracytoplasmic PAS-positive, diastase-resistant granules.
Alveolar soft part sarcoma. Typical organoid nests of eosinophilic tumour cells with abundant cytoplasm.

Q: The diagnosis of Alveolar Soft Part Sarcoma is genetically characterized by a t(X;17) translocation yielding an ASPSCR1-TFE3 fusion transcript, which corresponds to strong nuclear positivity for [...] on immunohistochemistry.
Alveolar soft part sarcoma. Partial karyotype of alveolar soft part sarcoma showing the characteristic alteration, der(17)t(X;17)(p11.2;q25).
Alveolar soft part sarcoma. Nuclear staining with TFE3 is characteristic.
A: TFE3
Back Extra: Alveolar Soft Part Sarcoma
- Clinical: Alveolar Soft Part Sarcoma (ASPS) typically presents as a slow-growing painless mass, and can involve the lungs, liver, bone, and brain with metastasis often occurring ≥ 10 years after diagnosis.
- Micro: ASPS is characterized by large polygonal cells with eosinophilic granular cytoplasm, arranged in a uniform organoid or nest-like pattern, creating a distinct alveolar architecture.
- Ancillary: Diagnosis of ASPS is confirmed by the presence of the TFE3 rearrangement or ASPSCR1-TFE3 fusion transcript, which is highly specific and sensitive for this tumour.
Reference Gallery:
Alveolar soft part sarcoma. Tumour involving fibula and calf muscles of a 13-year-old girl; postcontrast T1-weighted MRI images reveal a solid tumour with lobulated margins displaying inhomogeneous intense enhancement and a central non-enhancing component. Axial view.
Alveolar soft part sarcoma. Tumour involving fibula and calf muscles of a 13-year-old girl; postcontrast T1-weighted MRI images reveal a solid tumour with lobulated margins displaying inhomogeneous intense enhancement and a central non-enhancing component. Coronal view.
Alveolar soft part sarcoma. Compact cell nests outlined by sinusoidal vessels.
Alveolar soft part sarcoma. Alveolar-like structures, discohesive cells, and central or eccentric nuclei with prominent nucleoli.
Alveolar soft part sarcoma. Partial karyotype of alveolar soft part sarcoma showing the characteristic alteration, der(17)t(X;17)(p11.2;q25).
Alveolar soft part sarcoma. CD34 immunohistochemistry highlights the delicate capillaries surrounding the pseudoalveolar structures.
Alveolar soft part sarcoma. Nuclear staining with TFE3 is characteristic.
Alveolar soft part sarcoma. PASD staining. A large centrally placed cell shows elongated rod-like intracytoplasmic crystals in a sheaf-like arrangement; numerous surrounding cells show intracytoplasmic PAS-positive, diastase-resistant granules.
Alveolar soft part sarcoma. Typical organoid nests of eosinophilic tumour cells with abundant cytoplasm.

Q: A highly specific histologic finding in Alveolar Soft Part Sarcoma is the presence of rod-like or sheaf-like intracytoplasmic crystals that are classically [...].
Alveolar soft part sarcoma. PASD staining. A large centrally placed cell shows elongated rod-like intracytoplasmic crystals in a sheaf-like arrangement; numerous surrounding cells show intracytoplasmic PAS-positive, diastase-resistant granules.
A: PAS-positive, diastase-resistant
Back Extra: Alveolar Soft Part Sarcoma
- Clinical: Alveolar Soft Part Sarcoma (ASPS) typically presents as a slow-growing painless mass, and can involve the lungs, liver, bone, and brain with metastasis often occurring ≥ 10 years after diagnosis.
- Micro: ASPS is characterized by large polygonal cells with eosinophilic granular cytoplasm, arranged in a uniform organoid or nest-like pattern, creating a distinct alveolar architecture.
- Ancillary: Diagnosis of ASPS is confirmed by the presence of the TFE3 rearrangement or ASPSCR1-TFE3 fusion transcript, which is highly specific and sensitive for this tumour.
Reference Gallery:
Alveolar soft part sarcoma. Tumour involving fibula and calf muscles of a 13-year-old girl; postcontrast T1-weighted MRI images reveal a solid tumour with lobulated margins displaying inhomogeneous intense enhancement and a central non-enhancing component. Axial view.
Alveolar soft part sarcoma. Tumour involving fibula and calf muscles of a 13-year-old girl; postcontrast T1-weighted MRI images reveal a solid tumour with lobulated margins displaying inhomogeneous intense enhancement and a central non-enhancing component. Coronal view.
Alveolar soft part sarcoma. Compact cell nests outlined by sinusoidal vessels.
Alveolar soft part sarcoma. Alveolar-like structures, discohesive cells, and central or eccentric nuclei with prominent nucleoli.
Alveolar soft part sarcoma. Partial karyotype of alveolar soft part sarcoma showing the characteristic alteration, der(17)t(X;17)(p11.2;q25).
Alveolar soft part sarcoma. CD34 immunohistochemistry highlights the delicate capillaries surrounding the pseudoalveolar structures.
Alveolar soft part sarcoma. Nuclear staining with TFE3 is characteristic.
Alveolar soft part sarcoma. PASD staining. A large centrally placed cell shows elongated rod-like intracytoplasmic crystals in a sheaf-like arrangement; numerous surrounding cells show intracytoplasmic PAS-positive, diastase-resistant granules.
Alveolar soft part sarcoma. Typical organoid nests of eosinophilic tumour cells with abundant cytoplasm.

Q: Microscopically, [...] typically presents with a nested or fascicular architecture, pale eosinophilic cytoplasm, prominent macronucleoli, wreath-like multinucleated giant cells, and strong, diffuse S100 positivity.
Clear cell sarcoma. Tumour cells have pale eosinophilic cytoplasm with prominent nucleoli.
Clear cell sarcoma. Tumour cells show strong and diffuse expression of S100.
Clear cell sarcoma. Wreath-like multinucleated giant cells are a common finding.
A: Clear Cell Sarcoma of Soft Tissue
Back Extra: Clear Cell Sarcoma of Soft Tissue
- Clinical: Clear Cell Sarcoma of Soft Tissue mainly affects young adults, with a peak incidence in the third and fourth decades of life and a slight female predominance.
- Micro: Clear Cell Sarcoma of Soft Tissue exhibits a characteristic nested or fascicular architecture with palely eosinophilic cytoplasm and vesicular nuclei with macronucleoli.
- Ancillary: The genetic hallmark of Clear Cell Sarcoma of Soft Tissue is the reciprocal translocation t(12;22)(q13;q12), which fuses EWSR1 with ATF1.
Reference Gallery:
Clear cell sarcoma. Tumour cells have pale eosinophilic cytoplasm with prominent nucleoli.
Clear cell sarcoma. A subset of clear cell sarcomas have necrosis, which is an unfavourable prognostic factor.
Clear cell sarcoma. Tumour cells show strong and diffuse expression of S100.
Clear cell sarcoma. Wreath-like multinucleated giant cells are a common finding.
Clear cell sarcoma. This well-circumscribed tumour arose in the plantaris tendon of an 18-year-old woman. Despite the small size of the tumour, she died from disseminated metastases 4 years later.
Clear cell sarcoma of soft tissue. Schematic and partial G-banded karyotype of the 12;22 translocation in clear cell sarcoma.

Q: The defining genetic hallmark of Clear Cell Sarcoma of Soft Tissue is the reciprocal translocation t(12;22)(q13;q12), which results in the [ATF1] fusion gene.
Clear cell sarcoma of soft tissue. Schematic and partial G-banded karyotype of the 12;22 translocation in clear cell sarcoma.
A: EWSR1
Back Extra: Clear Cell Sarcoma of Soft Tissue
- Clinical: Clear Cell Sarcoma of Soft Tissue mainly affects young adults, with a peak incidence in the third and fourth decades of life and a slight female predominance.
- Micro: Clear Cell Sarcoma of Soft Tissue exhibits a characteristic nested or fascicular architecture with palely eosinophilic cytoplasm and vesicular nuclei with macronucleoli.
- Ancillary: The genetic hallmark of Clear Cell Sarcoma of Soft Tissue is the reciprocal translocation t(12;22)(q13;q12), which fuses EWSR1 with ATF1.
Reference Gallery:
Clear cell sarcoma. Tumour cells have pale eosinophilic cytoplasm with prominent nucleoli.
Clear cell sarcoma. A subset of clear cell sarcomas have necrosis, which is an unfavourable prognostic factor.
Clear cell sarcoma. Tumour cells show strong and diffuse expression of S100.
Clear cell sarcoma. Wreath-like multinucleated giant cells are a common finding.
Clear cell sarcoma. This well-circumscribed tumour arose in the plantaris tendon of an 18-year-old woman. Despite the small size of the tumour, she died from disseminated metastases 4 years later.
Clear cell sarcoma of soft tissue. Schematic and partial G-banded karyotype of the 12;22 translocation in clear cell sarcoma.

Q: Clinically, Clear Cell Sarcoma of Soft Tissue characteristically arises in deep soft tissues of young adults, with a striking predilection for the [...] and aponeuroses of the distal extremities.
Clear cell sarcoma. This well-circumscribed tumour arose in the plantaris tendon of an 18-year-old woman. Despite the small size of the tumour, she died from disseminated metastases 4 years later.
A: tendons
Back Extra: Clear Cell Sarcoma of Soft Tissue
- Clinical: Clear Cell Sarcoma of Soft Tissue mainly affects young adults, with a peak incidence in the third and fourth decades of life and a slight female predominance.
- Micro: Clear Cell Sarcoma of Soft Tissue exhibits a characteristic nested or fascicular architecture with palely eosinophilic cytoplasm and vesicular nuclei with macronucleoli.
- Ancillary: The genetic hallmark of Clear Cell Sarcoma of Soft Tissue is the reciprocal translocation t(12;22)(q13;q12), which fuses EWSR1 with ATF1.
Reference Gallery:
Clear cell sarcoma. Tumour cells have pale eosinophilic cytoplasm with prominent nucleoli.
Clear cell sarcoma. A subset of clear cell sarcomas have necrosis, which is an unfavourable prognostic factor.
Clear cell sarcoma. Tumour cells show strong and diffuse expression of S100.
Clear cell sarcoma. Wreath-like multinucleated giant cells are a common finding.
Clear cell sarcoma. This well-circumscribed tumour arose in the plantaris tendon of an 18-year-old woman. Despite the small size of the tumour, she died from disseminated metastases 4 years later.
Clear cell sarcoma of soft tissue. Schematic and partial G-banded karyotype of the 12;22 translocation in clear cell sarcoma.

Q: Clinically, [...] predominantly arises in the abdominal cavity of young males, often presenting grossly as a dominant mass with multiple smaller satellite nodules and a solid whitish-tan cut surface.
Desmoplastic small round cell tumour. CT image of a large pelvic desmoplastic small round cell tumour.
Desmoplastic small round cell tumour. Desmoplastic small round cell tumour presenting as one dominant tumour mass and multiple smaller tumour nodules. The cross-section shows a solid whitish-tan cut surface, with foci of necrosis.
A: desmoplastic small round cell tumor
Q: Desmoplastic Small Round Cell Tumour
- Clinical: [...] primarily affects children and young adults, with a male predominance, and is most commonly found in the abdominal cavity, presenting with pain, abdominal distention, and palpable masses.
- Micro: [...] is characterized by sharply outlined nests of small round cells in a prominent desmoplastic stroma, with frequent central necrosis and a solid growth pattern.
- Ancillary: [...] shows a distinctive multiphenotypic immunohistochemical profile, including positivity for cytokeratins, EMA, and desmin, and the presence of the EWSR1-WT1 gene fusion.
Reference Gallery:
Desmoplastic small round cell tumour. CT image of a large pelvic desmoplastic small round cell tumour.
Desmoplastic small round cell tumour. Desmoplastic small round cell tumour presenting as one dominant tumour mass and multiple smaller tumour nodules. The cross-section shows a solid whitish-tan cut surface, with foci of necrosis.
Desmoplastic small round cell tumour. Characteristic morphology with variably sized nests in a desmoplastic stroma.
Desmoplastic small round cell tumour. Solid growth pattern with large confluent nests.
Desmoplastic small round cell tumour. Infiltrative growth pattern and single-file appearance.
Desmoplastic small round cell tumour. Small round cells with minimal nuclear pleomorphism.
Desmoplastic small round cell tumour. Rosette formation.
Desmoplastic small round cell tumour. Focal necrosis.
Desmoplastic small round cell tumour. Glomeruloid vascular proliferation.
Desmoplastic small round cell tumour. Epithelial features with gland formation.
Desmoplastic small round cell tumour. Strong immunoreactivity for keratin.
Desmoplastic small round cell tumour. Strong immunoreactivity for desmin.
A: Desmoplastic small round cell tumour; Desmoplastic small round cell tumour; Desmoplastic small round cell tumour

Q: Histologically, [...] is characterized by sharply outlined nests of small round cells embedded in a prominent desmoplastic stroma, often accompanied by central necrosis.
Desmoplastic small round cell tumour. Characteristic morphology with variably sized nests in a desmoplastic stroma.
Desmoplastic small round cell tumour. Small round cells with minimal nuclear pleomorphism.
Desmoplastic small round cell tumour. Focal necrosis.
A: desmoplastic small round cell tumor
Q: Desmoplastic Small Round Cell Tumour
- Clinical: [...] primarily affects children and young adults, with a male predominance, and is most commonly found in the abdominal cavity, presenting with pain, abdominal distention, and palpable masses.
- Micro: [...] is characterized by sharply outlined nests of small round cells in a prominent desmoplastic stroma, with frequent central necrosis and a solid growth pattern.
- Ancillary: [...] shows a distinctive multiphenotypic immunohistochemical profile, including positivity for cytokeratins, EMA, and desmin, and the presence of the EWSR1-WT1 gene fusion.
Reference Gallery:
Desmoplastic small round cell tumour. CT image of a large pelvic desmoplastic small round cell tumour.
Desmoplastic small round cell tumour. Desmoplastic small round cell tumour presenting as one dominant tumour mass and multiple smaller tumour nodules. The cross-section shows a solid whitish-tan cut surface, with foci of necrosis.
Desmoplastic small round cell tumour. Characteristic morphology with variably sized nests in a desmoplastic stroma.
Desmoplastic small round cell tumour. Solid growth pattern with large confluent nests.
Desmoplastic small round cell tumour. Infiltrative growth pattern and single-file appearance.
Desmoplastic small round cell tumour. Small round cells with minimal nuclear pleomorphism.
Desmoplastic small round cell tumour. Rosette formation.
Desmoplastic small round cell tumour. Focal necrosis.
Desmoplastic small round cell tumour. Glomeruloid vascular proliferation.
Desmoplastic small round cell tumour. Epithelial features with gland formation.
Desmoplastic small round cell tumour. Strong immunoreactivity for keratin.
Desmoplastic small round cell tumour. Strong immunoreactivity for desmin.
A: Desmoplastic small round cell tumour; Desmoplastic small round cell tumour; Desmoplastic small round cell tumour

Q: A key diagnostic feature of desmoplastic small round cell tumor is its multiphenotypic immunohistochemical co-expression of cytokeratins and desmin, which is closely associated with the pathognomonic [...] gene fusion.
Desmoplastic small round cell tumour. Strong immunoreactivity for keratin.
Desmoplastic small round cell tumour. Strong immunoreactivity for desmin.
A: EWSR1-WT1
Q: Desmoplastic Small Round Cell Tumour
- Clinical: [...] primarily affects children and young adults, with a male predominance, and is most commonly found in the abdominal cavity, presenting with pain, abdominal distention, and palpable masses.
- Micro: [...] is characterized by sharply outlined nests of small round cells in a prominent desmoplastic stroma, with frequent central necrosis and a solid growth pattern.
- Ancillary: [...] shows a distinctive multiphenotypic immunohistochemical profile, including positivity for cytokeratins, EMA, and desmin, and the presence of the EWSR1-WT1 gene fusion.
Reference Gallery:
Desmoplastic small round cell tumour. CT image of a large pelvic desmoplastic small round cell tumour.
Desmoplastic small round cell tumour. Desmoplastic small round cell tumour presenting as one dominant tumour mass and multiple smaller tumour nodules. The cross-section shows a solid whitish-tan cut surface, with foci of necrosis.
Desmoplastic small round cell tumour. Characteristic morphology with variably sized nests in a desmoplastic stroma.
Desmoplastic small round cell tumour. Solid growth pattern with large confluent nests.
Desmoplastic small round cell tumour. Infiltrative growth pattern and single-file appearance.
Desmoplastic small round cell tumour. Small round cells with minimal nuclear pleomorphism.
Desmoplastic small round cell tumour. Rosette formation.
Desmoplastic small round cell tumour. Focal necrosis.
Desmoplastic small round cell tumour. Glomeruloid vascular proliferation.
Desmoplastic small round cell tumour. Epithelial features with gland formation.
Desmoplastic small round cell tumour. Strong immunoreactivity for keratin.
Desmoplastic small round cell tumour. Strong immunoreactivity for desmin.
A: Desmoplastic small round cell tumour; Desmoplastic small round cell tumour; Desmoplastic small round cell tumour

Q: In the classic (distal) subtype of Epithelioid Sarcoma, the microscopic architecture characteristically features cellular nodules with central necrosis, resulting in a [...] appearance.
Classic (distal-type) epithelioid sarcoma. Multiple ulcerating lesions on the sole of the foot.
Classic (distal-type) epithelioid sarcoma. Low-power magnification of a nodular lesion centered in the dermis composed of tumour cells surrounding an area of necrosis (pseudogranulomatous growth pattern).
A: pseudogranulomatous
Back Extra: Epithelioid Sarcoma
- Clinical: Epithelioid sarcoma (ES) presents as slow-growing, usually painless, firm nodules, often resulting in non-healing skin ulcers, particularly in the classic subtype.
- Micro: In the classic subtype of epithelioid sarcoma, the architecture shows cellular nodules with central necrosis, giving a pseudogranulomatous appearance.
- Ancillary: Immunohistochemistry shows positive staining for epithelial markers (keratin, EMA) and CD34, and a critical negative for SMARCB1 (INI1) in epithelioid sarcoma.
Reference Gallery:
Classic (distal-type) epithelioid sarcoma. Multiple ulcerating lesions on the sole of the foot.
Classic (distal-type) epithelioid sarcoma. Low-power magnification of a nodular lesion centered in the dermis composed of tumour cells surrounding an area of necrosis (pseudogranulomatous growth pattern).
Classic (distal-type) epithelioid sarcoma. Epithelioid tumour cells with abundant eosinophilic cytoplasm.
Classic (distal-type) epithelioid sarcoma. Cells with a plump spindle-shaped morphology.
Classic (distal-type) epithelioid sarcoma. Diffuse expression of keratin (CAM5.2).
Classic (distal-type) epithelioid sarcoma. Strong membranous immunopositivity for CD34.
Classic (distal-type) epithelioid sarcoma. Complete loss of SMARCB1 (INI1) protein expression in the tumour cells (blood vessels being internal positive controls).
Proximal-type (large cell) epithelioid sarcoma. Low-power magnification shows a multinodular growth pattern of epithelioid cells with foci of tumour necrosis.
Proximal-type (large cell) epithelioid sarcoma. Pleomorphic epithelioid tumour cells with abundant, deeply eosinophilic cytoplasm and enlarged vesicular nuclei with prominent nucleoli.
Proximal-type (large cell) epithelioid sarcoma. Aggregates of rhabdoid cells with glassy intracytoplasmic hyaline inclusions and eccentrically located, vesicular nuclei.

Q: Immunohistochemistry in Epithelioid Sarcoma typically demonstrates positivity for epithelial markers (keratin, EMA) and CD34, alongside a critical diagnostic loss of [...] protein expression.
Classic (distal-type) epithelioid sarcoma. Diffuse expression of keratin (CAM5.2).
Classic (distal-type) epithelioid sarcoma. Strong membranous immunopositivity for CD34.
Classic (distal-type) epithelioid sarcoma. Complete loss of SMARCB1 (INI1) protein expression in the tumour cells (blood vessels being internal positive controls).
A: SMARCB1 (INI1)
Back Extra: Epithelioid Sarcoma
- Clinical: Epithelioid sarcoma (ES) presents as slow-growing, usually painless, firm nodules, often resulting in non-healing skin ulcers, particularly in the classic subtype.
- Micro: In the classic subtype of epithelioid sarcoma, the architecture shows cellular nodules with central necrosis, giving a pseudogranulomatous appearance.
- Ancillary: Immunohistochemistry shows positive staining for epithelial markers (keratin, EMA) and CD34, and a critical negative for SMARCB1 (INI1) in epithelioid sarcoma.
Reference Gallery:
Classic (distal-type) epithelioid sarcoma. Multiple ulcerating lesions on the sole of the foot.
Classic (distal-type) epithelioid sarcoma. Low-power magnification of a nodular lesion centered in the dermis composed of tumour cells surrounding an area of necrosis (pseudogranulomatous growth pattern).
Classic (distal-type) epithelioid sarcoma. Epithelioid tumour cells with abundant eosinophilic cytoplasm.
Classic (distal-type) epithelioid sarcoma. Cells with a plump spindle-shaped morphology.
Classic (distal-type) epithelioid sarcoma. Diffuse expression of keratin (CAM5.2).
Classic (distal-type) epithelioid sarcoma. Strong membranous immunopositivity for CD34.
Classic (distal-type) epithelioid sarcoma. Complete loss of SMARCB1 (INI1) protein expression in the tumour cells (blood vessels being internal positive controls).
Proximal-type (large cell) epithelioid sarcoma. Low-power magnification shows a multinodular growth pattern of epithelioid cells with foci of tumour necrosis.
Proximal-type (large cell) epithelioid sarcoma. Pleomorphic epithelioid tumour cells with abundant, deeply eosinophilic cytoplasm and enlarged vesicular nuclei with prominent nucleoli.
Proximal-type (large cell) epithelioid sarcoma. Aggregates of rhabdoid cells with glassy intracytoplasmic hyaline inclusions and eccentrically located, vesicular nuclei.

Q: The proximal (large cell) variant of Epithelioid Sarcoma is characterized by pleomorphic tumor cells and prominent aggregates of [...] cells containing glassy intracytoplasmic hyaline inclusions.
Proximal-type (large cell) epithelioid sarcoma. Low-power magnification shows a multinodular growth pattern of epithelioid cells with foci of tumour necrosis.
Proximal-type (large cell) epithelioid sarcoma. Aggregates of rhabdoid cells with glassy intracytoplasmic hyaline inclusions and eccentrically located, vesicular nuclei.
A: rhabdoid
Back Extra: Epithelioid Sarcoma
- Clinical: Epithelioid sarcoma (ES) presents as slow-growing, usually painless, firm nodules, often resulting in non-healing skin ulcers, particularly in the classic subtype.
- Micro: In the classic subtype of epithelioid sarcoma, the architecture shows cellular nodules with central necrosis, giving a pseudogranulomatous appearance.
- Ancillary: Immunohistochemistry shows positive staining for epithelial markers (keratin, EMA) and CD34, and a critical negative for SMARCB1 (INI1) in epithelioid sarcoma.
Reference Gallery:
Classic (distal-type) epithelioid sarcoma. Multiple ulcerating lesions on the sole of the foot.
Classic (distal-type) epithelioid sarcoma. Low-power magnification of a nodular lesion centered in the dermis composed of tumour cells surrounding an area of necrosis (pseudogranulomatous growth pattern).
Classic (distal-type) epithelioid sarcoma. Epithelioid tumour cells with abundant eosinophilic cytoplasm.
Classic (distal-type) epithelioid sarcoma. Cells with a plump spindle-shaped morphology.
Classic (distal-type) epithelioid sarcoma. Diffuse expression of keratin (CAM5.2).
Classic (distal-type) epithelioid sarcoma. Strong membranous immunopositivity for CD34.
Classic (distal-type) epithelioid sarcoma. Complete loss of SMARCB1 (INI1) protein expression in the tumour cells (blood vessels being internal positive controls).
Proximal-type (large cell) epithelioid sarcoma. Low-power magnification shows a multinodular growth pattern of epithelioid cells with foci of tumour necrosis.
Proximal-type (large cell) epithelioid sarcoma. Pleomorphic epithelioid tumour cells with abundant, deeply eosinophilic cytoplasm and enlarged vesicular nuclei with prominent nucleoli.
Proximal-type (large cell) epithelioid sarcoma. Aggregates of rhabdoid cells with glassy intracytoplasmic hyaline inclusions and eccentrically located, vesicular nuclei.

Q: Histologically, Extrarenal Rhabdoid Tumor is characterized by discohesive cells with eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm containing characteristic [...].
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. Rhabdoid cells show a discohesive growth pattern.
A: glassy inclusion-like bodies
Back Extra: Extrarenal Rhabdoid Tumour
- Clinical: Most cases present as a rapidly enlarging soft tissue mass, with clinical symptoms depending on the primary organ involvement. Particularly in infants, some cases present with disseminated disease without an obvious primary tumour.
- Micro: The tumour is characterized by rhabdoid cells with large vesicular rounded to bean-shaped nuclei, prominent nucleoli, and abundant cytoplasm, arranged in sheets or in a solid trabecular pattern.
- Ancillary: Essential for diagnosis: primitive undifferentiated or rhabdoid cell morphology; loss of expression of SMARCB1 (INI1). Approximately 98% of extrarenal rhabdoid tumours demonstrate genomic alterations of both copies of the SMARCB1 gene.
Reference Gallery:
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. Rhabdoid cells show a discohesive growth pattern.
Extrarenal rhabdoid tumour. Proliferation of undifferentiated small round cells, which is often observed in liver tumour.
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin CAM5.2, which is confined to the inclusions.
Extrarenal rhabdoid tumour. Focal membranous positivity for EMA.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) protein is observed in the vascular endothelial cells and inflammatory cells but is completely absent in the tumour cells.
Extrarenal rhabdoid tumour. Next-generation sequencing analysis demonstrating a SMARCB1 nonsense mutation (NM_003073.4:c.778C>T, p.Gln260*) in a rhabdoid tumour with copy-neutral loss of heterozygosity of chromosome 22 (not shown). The mutant base is highlighted in yellow; sequencing reads are visualized with custom software (Genetrix).
Congenital extrarenal rhabdoid tumour. In this neonatal patient, a huge paravertebral and retroperitoneal tumour is evident. Multiple metastatic lesions were also identified at birth.

Q: An essential diagnostic finding in Extrarenal Rhabdoid Tumor is the immunohistochemical loss of nuclear expression of [...], which is reliably retained in background endothelial and inflammatory cells.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) protein is observed in the vascular endothelial cells and inflammatory cells but is completely absent in the tumour cells.
A: SMARCB1 (INI1)
Back Extra: Extrarenal Rhabdoid Tumour
- Clinical: Most cases present as a rapidly enlarging soft tissue mass, with clinical symptoms depending on the primary organ involvement. Particularly in infants, some cases present with disseminated disease without an obvious primary tumour.
- Micro: The tumour is characterized by rhabdoid cells with large vesicular rounded to bean-shaped nuclei, prominent nucleoli, and abundant cytoplasm, arranged in sheets or in a solid trabecular pattern.
- Ancillary: Essential for diagnosis: primitive undifferentiated or rhabdoid cell morphology; loss of expression of SMARCB1 (INI1). Approximately 98% of extrarenal rhabdoid tumours demonstrate genomic alterations of both copies of the SMARCB1 gene.
Reference Gallery:
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. Rhabdoid cells show a discohesive growth pattern.
Extrarenal rhabdoid tumour. Proliferation of undifferentiated small round cells, which is often observed in liver tumour.
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin CAM5.2, which is confined to the inclusions.
Extrarenal rhabdoid tumour. Focal membranous positivity for EMA.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) protein is observed in the vascular endothelial cells and inflammatory cells but is completely absent in the tumour cells.
Extrarenal rhabdoid tumour. Next-generation sequencing analysis demonstrating a SMARCB1 nonsense mutation (NM_003073.4:c.778C>T, p.Gln260*) in a rhabdoid tumour with copy-neutral loss of heterozygosity of chromosome 22 (not shown). The mutant base is highlighted in yellow; sequencing reads are visualized with custom software (Genetrix).
Congenital extrarenal rhabdoid tumour. In this neonatal patient, a huge paravertebral and retroperitoneal tumour is evident. Multiple metastatic lesions were also identified at birth.

Q: In Extrarenal Rhabdoid Tumor, the distinctive cytoplasmic inclusions frequently demonstrate strong, localized immunoreactivity for cytokeratin markers such as [...].
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin CAM5.2, which is confined to the inclusions.
A: CAM5.2
Back Extra: Extrarenal Rhabdoid Tumour
- Clinical: Most cases present as a rapidly enlarging soft tissue mass, with clinical symptoms depending on the primary organ involvement. Particularly in infants, some cases present with disseminated disease without an obvious primary tumour.
- Micro: The tumour is characterized by rhabdoid cells with large vesicular rounded to bean-shaped nuclei, prominent nucleoli, and abundant cytoplasm, arranged in sheets or in a solid trabecular pattern.
- Ancillary: Essential for diagnosis: primitive undifferentiated or rhabdoid cell morphology; loss of expression of SMARCB1 (INI1). Approximately 98% of extrarenal rhabdoid tumours demonstrate genomic alterations of both copies of the SMARCB1 gene.
Reference Gallery:
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. Rhabdoid cells show a discohesive growth pattern.
Extrarenal rhabdoid tumour. Proliferation of undifferentiated small round cells, which is often observed in liver tumour.
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin CAM5.2, which is confined to the inclusions.
Extrarenal rhabdoid tumour. Focal membranous positivity for EMA.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) protein is observed in the vascular endothelial cells and inflammatory cells but is completely absent in the tumour cells.
Extrarenal rhabdoid tumour. Next-generation sequencing analysis demonstrating a SMARCB1 nonsense mutation (NM_003073.4:c.778C>T, p.Gln260*) in a rhabdoid tumour with copy-neutral loss of heterozygosity of chromosome 22 (not shown). The mutant base is highlighted in yellow; sequencing reads are visualized with custom software (Genetrix).
Congenital extrarenal rhabdoid tumour. In this neonatal patient, a huge paravertebral and retroperitoneal tumour is evident. Multiple metastatic lesions were also identified at birth.

Q: Histologically, [...] is characterized by a multinodular architecture composed of an abundant myxoid matrix containing interconnecting cords of uniform cells, often with long, delicate cytoplasmic processes.
Extraskeletal myxoid chondrosarcoma. Nodular architecture; thick fibrous bands separate pools of myxoid stroma containing tumour cells. Chronic inflammation and focal haemorrhage may be seen.
Extraskeletal myxoid chondrosarcoma. The tumour is characterized by abundant myxoid matrix and interconnecting cords of uniform cells, often with long, delicate processes.
A: Extraskeletal Myxoid Chondrosarcoma
Q: Extraskeletal Myxoid Chondrosarcoma
- Clinical: Patients with [...] often present with a deep-seated, painful soft tissue mass, particularly in adults around the age of 50.
- Micro: The hallmark of [...] is the presence of abundant myxoid matrix with cords and clusters of uniform cells, often with delicate cytoplasmic processes.
- Ancillary: Identification of [...] is aided by the presence of NR4A3 gene rearrangement, which is a key diagnostic marker.
Reference Gallery:
Extraskeletal myxoid chondrosarcoma. Schematic of the four known NR4A3 gene fusions and their respective chromosomal locations.
Extraskeletal myxoid chondrosarcoma. Nodular architecture; thick fibrous bands separate pools of myxoid stroma containing tumour cells. Chronic inflammation and focal haemorrhage may be seen.
Extraskeletal myxoid chondrosarcoma. The tumour is characterized by abundant myxoid matrix and interconnecting cords of uniform cells, often with long, delicate processes.
Extraskeletal myxoid chondrosarcoma. Spindle cell differentiation is common and when present can be either focal or diffuse. Note the interconnecting growth pattern.
Extraskeletal myxoid chondrosarcoma. The cells sometimes form cohesive clusters and ring-forms mimicking an epithelial neoplasm, most importantly a myoepithelial tumour.
Extraskeletal myxoid chondrosarcoma. The cellular subtype of extraskeletal myxoid chondrosarcoma is characterized by sheets and cords of cells with little intervening myxoid matrix. The cells frequently have an epithelioid morphology and large vesicular nuclei, prominent nucleoli, and brisk mitotic activity.
Extraskeletal myxoid chondrosarcoma. Rhabdoid cells with eccentric eosinophilic cytoplasm and perinuclear hyaline globules are seen in some extraskeletal myxoid chondrosarcomas. These cells are frequently negative for SMARCB1 (INI1) by immunohistochemistry.
Extraskeletal myxoid chondrosarcoma. T2-weighted axial MRI highlights the hyperintense signalling and pronounced lobular architecture in an extraskeletal myxoid chondrosarcoma of the thigh.
Extraskeletal myxoid chondrosarcoma. Grossly, these tumours are well demarcated, are contained by a pseudocapsule, and have a lobular architecture defined by fibrous septa.
Extraskeletal myxoid chondrosarcoma. Cystic cavities, haemorrhage, and necrosis are often found on the cut surface. Note the well-defined lobular architecture and thick fibrous septa.
A: Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Myxoid Chondrosarcoma

Q: The defining molecular hallmark of Extraskeletal Myxoid Chondrosarcoma is a recurrent gene rearrangement involving the [...] gene.
Extraskeletal myxoid chondrosarcoma. Schematic of the four known NR4A3 gene fusions and their respective chromosomal locations.
A: NR4A3
Q: Extraskeletal Myxoid Chondrosarcoma
- Clinical: Patients with [...] often present with a deep-seated, painful soft tissue mass, particularly in adults around the age of 50.
- Micro: The hallmark of [...] is the presence of abundant myxoid matrix with cords and clusters of uniform cells, often with delicate cytoplasmic processes.
- Ancillary: Identification of [...] is aided by the presence of NR4A3 gene rearrangement, which is a key diagnostic marker.
Reference Gallery:
Extraskeletal myxoid chondrosarcoma. Schematic of the four known NR4A3 gene fusions and their respective chromosomal locations.
Extraskeletal myxoid chondrosarcoma. Nodular architecture; thick fibrous bands separate pools of myxoid stroma containing tumour cells. Chronic inflammation and focal haemorrhage may be seen.
Extraskeletal myxoid chondrosarcoma. The tumour is characterized by abundant myxoid matrix and interconnecting cords of uniform cells, often with long, delicate processes.
Extraskeletal myxoid chondrosarcoma. Spindle cell differentiation is common and when present can be either focal or diffuse. Note the interconnecting growth pattern.
Extraskeletal myxoid chondrosarcoma. The cells sometimes form cohesive clusters and ring-forms mimicking an epithelial neoplasm, most importantly a myoepithelial tumour.
Extraskeletal myxoid chondrosarcoma. The cellular subtype of extraskeletal myxoid chondrosarcoma is characterized by sheets and cords of cells with little intervening myxoid matrix. The cells frequently have an epithelioid morphology and large vesicular nuclei, prominent nucleoli, and brisk mitotic activity.
Extraskeletal myxoid chondrosarcoma. Rhabdoid cells with eccentric eosinophilic cytoplasm and perinuclear hyaline globules are seen in some extraskeletal myxoid chondrosarcomas. These cells are frequently negative for SMARCB1 (INI1) by immunohistochemistry.
Extraskeletal myxoid chondrosarcoma. T2-weighted axial MRI highlights the hyperintense signalling and pronounced lobular architecture in an extraskeletal myxoid chondrosarcoma of the thigh.
Extraskeletal myxoid chondrosarcoma. Grossly, these tumours are well demarcated, are contained by a pseudocapsule, and have a lobular architecture defined by fibrous septa.
Extraskeletal myxoid chondrosarcoma. Cystic cavities, haemorrhage, and necrosis are often found on the cut surface. Note the well-defined lobular architecture and thick fibrous septa.
A: Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Myxoid Chondrosarcoma

Q: Grossly and radiographically, a well-demarcated soft tissue tumor with a pronounced lobular architecture separated by thick fibrous septa, often demonstrating cystic cavities and hemorrhage, is highly characteristic of [...].
Extraskeletal myxoid chondrosarcoma. T2-weighted axial MRI highlights the hyperintense signalling and pronounced lobular architecture in an extraskeletal myxoid chondrosarcoma of the thigh.
Extraskeletal myxoid chondrosarcoma. Grossly, these tumours are well demarcated, are contained by a pseudocapsule, and have a lobular architecture defined by fibrous septa.
Extraskeletal myxoid chondrosarcoma. Cystic cavities, haemorrhage, and necrosis are often found on the cut surface. Note the well-defined lobular architecture and thick fibrous septa.
A: Extraskeletal Myxoid Chondrosarcoma
Q: Extraskeletal Myxoid Chondrosarcoma
- Clinical: Patients with [...] often present with a deep-seated, painful soft tissue mass, particularly in adults around the age of 50.
- Micro: The hallmark of [...] is the presence of abundant myxoid matrix with cords and clusters of uniform cells, often with delicate cytoplasmic processes.
- Ancillary: Identification of [...] is aided by the presence of NR4A3 gene rearrangement, which is a key diagnostic marker.
Reference Gallery:
Extraskeletal myxoid chondrosarcoma. Schematic of the four known NR4A3 gene fusions and their respective chromosomal locations.
Extraskeletal myxoid chondrosarcoma. Nodular architecture; thick fibrous bands separate pools of myxoid stroma containing tumour cells. Chronic inflammation and focal haemorrhage may be seen.
Extraskeletal myxoid chondrosarcoma. The tumour is characterized by abundant myxoid matrix and interconnecting cords of uniform cells, often with long, delicate processes.
Extraskeletal myxoid chondrosarcoma. Spindle cell differentiation is common and when present can be either focal or diffuse. Note the interconnecting growth pattern.
Extraskeletal myxoid chondrosarcoma. The cells sometimes form cohesive clusters and ring-forms mimicking an epithelial neoplasm, most importantly a myoepithelial tumour.
Extraskeletal myxoid chondrosarcoma. The cellular subtype of extraskeletal myxoid chondrosarcoma is characterized by sheets and cords of cells with little intervening myxoid matrix. The cells frequently have an epithelioid morphology and large vesicular nuclei, prominent nucleoli, and brisk mitotic activity.
Extraskeletal myxoid chondrosarcoma. Rhabdoid cells with eccentric eosinophilic cytoplasm and perinuclear hyaline globules are seen in some extraskeletal myxoid chondrosarcomas. These cells are frequently negative for SMARCB1 (INI1) by immunohistochemistry.
Extraskeletal myxoid chondrosarcoma. T2-weighted axial MRI highlights the hyperintense signalling and pronounced lobular architecture in an extraskeletal myxoid chondrosarcoma of the thigh.
Extraskeletal myxoid chondrosarcoma. Grossly, these tumours are well demarcated, are contained by a pseudocapsule, and have a lobular architecture defined by fibrous septa.
Extraskeletal myxoid chondrosarcoma. Cystic cavities, haemorrhage, and necrosis are often found on the cut surface. Note the well-defined lobular architecture and thick fibrous septa.
A: Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Myxoid Chondrosarcoma

Q: The most common histological pattern of Extraskeletal Osteosarcoma is the osteoblastic type, characterized by malignant spindle or polygonal cells directly producing [...] or lace-like neoplastic bone.
Extraskeletal osteosarcoma. Osteoblastic type with tumour cells producing lace-like neoplastic bone.
A: osteoid
Back Extra: Extraskeletal Osteosarcoma
- Clinical: Most patients present with a progressively enlarging mass that may be associated with pain. Some patients present with lung metastases.
- Micro: The osteoblastic type is the most common, characterized by spindle or polygonal cells producing osteoid or bone matrix.
- Ancillary: Recurrent copy-number losses in tumour suppressor genes (CDKN2A, TP53, RB1) and gains in oncogenes (RUNX2, CDC5L, COPS3) are common.
Reference Gallery:
Extraskeletal osteosarcoma. The bone is more prominent in the centre of the tumour.
Extraskeletal osteosarcoma. Osteoblastic type with tumour cells producing lace-like neoplastic bone.
Extraskeletal osteosarcoma. Gross photograph showing a large heterogeneous tan-white fleshy tumour with haemorrhagic and cystic spaces.
Extraskeletal osteosarcoma. Chondroblastic type. Condensation and spindling of the tumour cells are shown at the periphery of the cartilaginous area.
Extraskeletal osteosarcoma. Fibroblastic type composed of intersecting fascicles of tumour cells with focus of neoplastic bone.
Extraskeletal osteosarcoma. Axial contrast-enhanced CT of the pelvis shows a subcutaneous soft tissue mass superficial to the right gluteal musculature. Dense mineralization is seen centrally.

Q: Unlike myositis ossificans which exhibits peripheral maturation, the dense mineralization and neoplastic bone in Extraskeletal Osteosarcoma are characteristically most prominent in the [...] of the tumor.
Extraskeletal osteosarcoma. The bone is more prominent in the centre of the tumour.
Extraskeletal osteosarcoma. Axial contrast-enhanced CT of the pelvis shows a subcutaneous soft tissue mass superficial to the right gluteal musculature. Dense mineralization is seen centrally.
A: center
Back Extra: Extraskeletal Osteosarcoma
- Clinical: Most patients present with a progressively enlarging mass that may be associated with pain. Some patients present with lung metastases.
- Micro: The osteoblastic type is the most common, characterized by spindle or polygonal cells producing osteoid or bone matrix.
- Ancillary: Recurrent copy-number losses in tumour suppressor genes (CDKN2A, TP53, RB1) and gains in oncogenes (RUNX2, CDC5L, COPS3) are common.
Reference Gallery:
Extraskeletal osteosarcoma. The bone is more prominent in the centre of the tumour.
Extraskeletal osteosarcoma. Osteoblastic type with tumour cells producing lace-like neoplastic bone.
Extraskeletal osteosarcoma. Gross photograph showing a large heterogeneous tan-white fleshy tumour with haemorrhagic and cystic spaces.
Extraskeletal osteosarcoma. Chondroblastic type. Condensation and spindling of the tumour cells are shown at the periphery of the cartilaginous area.
Extraskeletal osteosarcoma. Fibroblastic type composed of intersecting fascicles of tumour cells with focus of neoplastic bone.
Extraskeletal osteosarcoma. Axial contrast-enhanced CT of the pelvis shows a subcutaneous soft tissue mass superficial to the right gluteal musculature. Dense mineralization is seen centrally.

Q: Histopathologically, NTRK-rearranged spindle cell neoplasm (emerging) features monomorphic spindle cells with thick stromal collagen and frequently infiltrates subcutaneous fat in a reticular fashion reminiscent of [...].
NTRK-rearranged spindle cell neoplasm. Spindle cell tumour infiltrating fat in a reticular fashion reminiscent of lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Monomorphic spindle cell tumour with patternless architecture and distinctive stromal and perivascular collagen deposition.
NTRK-rearranged spindle cell neoplasm. Area with increased cellularity and thick stromal collagen bands.
A: lipofibromatosis
Back Extra: NTRK-rearranged spindle cell neoplasm (emerging)
- Clinical: Most tumours present as a palpable, non-tender mass in the extremities or trunk, predominantly in the first two decades of life.
- Micro: Histopathology shows a monomorphic spindle cell phenotype, variable stromal hyalinization, and infiltrative growth within subcutaneous fat.
- Ancillary: Tumours with NTRK fusions are reactive with an anti–pan-TRK monoclonal antibody, with cytoplasmic or nuclear staining.
Reference Gallery:
NTRK-rearranged spindle cell neoplasm. Spindle cell tumour infiltrating fat in a reticular fashion reminiscent of lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Monomorphic spindle cell tumour with patternless architecture and distinctive stromal and perivascular collagen deposition.
NTRK-rearranged spindle cell neoplasm. CD34 expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. S100 expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. TRK-A/B/C expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. Area with increased cellularity and thick stromal collagen bands.
NTRK-rearranged spindle cell neoplasm. Area with increased cellularity and thick stromal collagen bands.

Q: The defining ancillary feature of NTRK-rearranged spindle cell neoplasm (emerging) is characteristic cytoplasmic or nuclear immunoreactivity with monoclonal antibodies directed against [...].
NTRK-rearranged spindle cell neoplasm. TRK-A/B/C expression by immunohistochemistry.
A: pan-TRK
Back Extra: NTRK-rearranged spindle cell neoplasm (emerging)
- Clinical: Most tumours present as a palpable, non-tender mass in the extremities or trunk, predominantly in the first two decades of life.
- Micro: Histopathology shows a monomorphic spindle cell phenotype, variable stromal hyalinization, and infiltrative growth within subcutaneous fat.
- Ancillary: Tumours with NTRK fusions are reactive with an anti–pan-TRK monoclonal antibody, with cytoplasmic or nuclear staining.
Reference Gallery:
NTRK-rearranged spindle cell neoplasm. Spindle cell tumour infiltrating fat in a reticular fashion reminiscent of lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Monomorphic spindle cell tumour with patternless architecture and distinctive stromal and perivascular collagen deposition.
NTRK-rearranged spindle cell neoplasm. CD34 expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. S100 expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. TRK-A/B/C expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. Area with increased cellularity and thick stromal collagen bands.
NTRK-rearranged spindle cell neoplasm. Area with increased cellularity and thick stromal collagen bands.

Q: In addition to TRK positivity, the spindle cells of NTRK-rearranged spindle cell neoplasm (emerging) typically demonstrate immunohistochemical co-expression of [...].
NTRK-rearranged spindle cell neoplasm. CD34 expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. S100 expression by immunohistochemistry.
A: S100 and CD34
Back Extra: NTRK-rearranged spindle cell neoplasm (emerging)
- Clinical: Most tumours present as a palpable, non-tender mass in the extremities or trunk, predominantly in the first two decades of life.
- Micro: Histopathology shows a monomorphic spindle cell phenotype, variable stromal hyalinization, and infiltrative growth within subcutaneous fat.
- Ancillary: Tumours with NTRK fusions are reactive with an anti–pan-TRK monoclonal antibody, with cytoplasmic or nuclear staining.
Reference Gallery:
NTRK-rearranged spindle cell neoplasm. Spindle cell tumour infiltrating fat in a reticular fashion reminiscent of lipofibromatosis.
NTRK-rearranged spindle cell neoplasm. Monomorphic spindle cell tumour with patternless architecture and distinctive stromal and perivascular collagen deposition.
NTRK-rearranged spindle cell neoplasm. CD34 expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. S100 expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. TRK-A/B/C expression by immunohistochemistry.
NTRK-rearranged spindle cell neoplasm. Area with increased cellularity and thick stromal collagen bands.
NTRK-rearranged spindle cell neoplasm. Area with increased cellularity and thick stromal collagen bands.

Q: Morphologically, monophasic Synovial Sarcoma typically presents as a tumor with fascicles of [...], often accompanied by characteristic wiry collagen and occasional calcifications.
Monophasic synovial sarcoma. Tumour with fascicles of monomorphic blue spindle cells.
Monophasic synovial sarcoma. Tumour area with wiry collagen.
Monophasic synovial sarcoma. Tumour area with calcifications.
A: monomorphic blue spindle cells
Back Extra: Synovial Sarcoma
- Clinical: Synovial sarcoma (SS) usually presents as a slow-growing, painful swelling, often with radiologically detectable stippled or spiculated calcification.
- Micro: Monophasic SS is characterized by fascicles of monomorphic blue spindle cells, with occasional areas of calcification, myxoid change, and wiry collagen.
- Ancillary: SS is defined by the presence of the SS18-SSX1/2/4 fusion gene, detectable by FISH, and is often positive for TLE1 nuclear staining by immunohistochemistry.
Reference Gallery:
Monophasic synovial sarcoma. Tumour with fascicles of monomorphic blue spindle cells.
Monophasic synovial sarcoma. Tumour area with wiry collagen.
Monophasic synovial sarcoma. Tumour area with calcifications.
Monophasic synovial sarcoma. Tumour area with myxoid change.
Poorly differentiated synovial sarcoma. Hypercellular fascicular tumour resembling malignant peripheral nerve sheath tumour.
Poorly differentiated synovial sarcoma. Round cell tumour resembling Ewing sarcoma.
Synovial sarcoma. Immunohistochemistry: multifocal EMA expression.
Synovial sarcoma. Immunohistochemistry: diffuse and strong TLE1 nuclear staining.
Synovial sarcoma. Graphical representation of interrelationships of fusion type to tumour histology and patient sex in synovial sarcoma. Most synovial sarcomas are monophasic, and the SS18-SSX1 fusion type is more common than SS18-SSX2. Men and women are affected in approximately even proportions, but men show a 3:2 ratio of SS18-SSX1 to SS18-SSX2, whereas in women the ratio is close to 1:1. The vast majority of SS18-SSX2 cases show monophasic histology, whereas most biphasic cases show SS18-SSX1. Biphasic synovial sarcomas harbouring the SS18-SSX2 fusion are uncommon, and the diagnosis of such cases should therefore be well supported.

Q: By immunohistochemistry, Synovial Sarcoma characteristically exhibits diffuse and strong nuclear positivity for [...].
Synovial sarcoma. Immunohistochemistry: diffuse and strong TLE1 nuclear staining.
A: TLE1
Back Extra: Synovial Sarcoma
- Clinical: Synovial sarcoma (SS) usually presents as a slow-growing, painful swelling, often with radiologically detectable stippled or spiculated calcification.
- Micro: Monophasic SS is characterized by fascicles of monomorphic blue spindle cells, with occasional areas of calcification, myxoid change, and wiry collagen.
- Ancillary: SS is defined by the presence of the SS18-SSX1/2/4 fusion gene, detectable by FISH, and is often positive for TLE1 nuclear staining by immunohistochemistry.
Reference Gallery:
Monophasic synovial sarcoma. Tumour with fascicles of monomorphic blue spindle cells.
Monophasic synovial sarcoma. Tumour area with wiry collagen.
Monophasic synovial sarcoma. Tumour area with calcifications.
Monophasic synovial sarcoma. Tumour area with myxoid change.
Poorly differentiated synovial sarcoma. Hypercellular fascicular tumour resembling malignant peripheral nerve sheath tumour.
Poorly differentiated synovial sarcoma. Round cell tumour resembling Ewing sarcoma.
Synovial sarcoma. Immunohistochemistry: multifocal EMA expression.
Synovial sarcoma. Immunohistochemistry: diffuse and strong TLE1 nuclear staining.
Synovial sarcoma. Graphical representation of interrelationships of fusion type to tumour histology and patient sex in synovial sarcoma. Most synovial sarcomas are monophasic, and the SS18-SSX1 fusion type is more common than SS18-SSX2. Men and women are affected in approximately even proportions, but men show a 3:2 ratio of SS18-SSX1 to SS18-SSX2, whereas in women the ratio is close to 1:1. The vast majority of SS18-SSX2 cases show monophasic histology, whereas most biphasic cases show SS18-SSX1. Biphasic synovial sarcomas harbouring the SS18-SSX2 fusion are uncommon, and the diagnosis of such cases should therefore be well supported.

Q: The defining molecular aberration in Synovial Sarcoma is the presence of the [...] fusion gene (most commonly involving subtypes 1, 2, or 4).
Synovial sarcoma. Graphical representation of interrelationships of fusion type to tumour histology and patient sex in synovial sarcoma. Most synovial sarcomas are monophasic, and the SS18-SSX1 fusion type is more common than SS18-SSX2. Men and women are affected in approximately even proportions, but men show a 3:2 ratio of SS18-SSX1 to SS18-SSX2, whereas in women the ratio is close to 1:1. The vast majority of SS18-SSX2 cases show monophasic histology, whereas most biphasic cases show SS18-SSX1. Biphasic synovial sarcomas harbouring the SS18-SSX2 fusion are uncommon, and the diagnosis of such cases should therefore be well supported.
A: SS18-SSX
Back Extra: Synovial Sarcoma
- Clinical: Synovial sarcoma (SS) usually presents as a slow-growing, painful swelling, often with radiologically detectable stippled or spiculated calcification.
- Micro: Monophasic SS is characterized by fascicles of monomorphic blue spindle cells, with occasional areas of calcification, myxoid change, and wiry collagen.
- Ancillary: SS is defined by the presence of the SS18-SSX1/2/4 fusion gene, detectable by FISH, and is often positive for TLE1 nuclear staining by immunohistochemistry.
Reference Gallery:
Monophasic synovial sarcoma. Tumour with fascicles of monomorphic blue spindle cells.
Monophasic synovial sarcoma. Tumour area with wiry collagen.
Monophasic synovial sarcoma. Tumour area with calcifications.
Monophasic synovial sarcoma. Tumour area with myxoid change.
Poorly differentiated synovial sarcoma. Hypercellular fascicular tumour resembling malignant peripheral nerve sheath tumour.
Poorly differentiated synovial sarcoma. Round cell tumour resembling Ewing sarcoma.
Synovial sarcoma. Immunohistochemistry: multifocal EMA expression.
Synovial sarcoma. Immunohistochemistry: diffuse and strong TLE1 nuclear staining.
Synovial sarcoma. Graphical representation of interrelationships of fusion type to tumour histology and patient sex in synovial sarcoma. Most synovial sarcomas are monophasic, and the SS18-SSX1 fusion type is more common than SS18-SSX2. Men and women are affected in approximately even proportions, but men show a 3:2 ratio of SS18-SSX1 to SS18-SSX2, whereas in women the ratio is close to 1:1. The vast majority of SS18-SSX2 cases show monophasic histology, whereas most biphasic cases show SS18-SSX1. Biphasic synovial sarcomas harbouring the SS18-SSX2 fusion are uncommon, and the diagnosis of such cases should therefore be well supported.

Q: Microscopically, the pleomorphic variant of Undifferentiated Sarcoma is typically composed of a spindle and pleomorphic cell population characterized by a high mitotic rate and frequent [...].
Undifferentiated pleomorphic sarcoma. Undifferentiated pleomorphic sarcoma is composed of a spindle cell and pleomorphic cell population most often characterized by high mitotic activity. Atypical mitoses are very common.
A: atypical mitoses
Back Extra: Undifferentiated Sarcoma
- Clinical: Undifferentiated sarcomas often present with a rapidly growing mass, and are found in various anatomical locations with no sex predilection.
- Micro: Pleomorphic undifferentiated sarcomas are characterized by a high mitotic rate, atypical mitoses, and a lack of specific differentiation.
- Ancillary: Undifferentiated pleomorphic sarcomas exhibit complex genetic aberrations with extensive genomic rearrangements and copy-number changes.
Reference Gallery:
Undifferentiated pleomorphic sarcoma. Circos plot illustrating the complex copy-number and rearrangement patterns seen in a typical undifferentiated pleomorphic sarcoma genome. The outer ring denotes chromosomal location, with subsequent rings representing single-nucleotide variants, insertions, deletions, and copy-number gains and losses. The arcs represent interchromosomal and intrachromosomal rearrangements.
Undifferentiated pleomorphic sarcoma. Grossly, undifferentiated pleomorphic sarcomas most often feature a fleshy appearance with areas of necrosis and haemorrhage.
Undifferentiated pleomorphic sarcoma. Undifferentiated pleomorphic sarcoma is composed of a spindle cell and pleomorphic cell population most often characterized by high mitotic activity. Atypical mitoses are very common.
Undifferentiated spindle cell sarcoma. Undifferentiated spindle cell sarcoma features a highly atypical spindle cell proliferation. Mitotic activity is most often high.
Undifferentiated round cell sarcoma. Currently, undifferentiated round cell sarcoma can be diagnosed only if distinctive gene fusions have been ruled out.
Undifferentiated epithelioid sarcoma. Undifferentiated epithelioid sarcoma is most often composed of a high-grade epithelioid cell population lacking any specific line of differentiation.

Q: Genomically, the pleomorphic variant of Undifferentiated Sarcoma lacks a single defining mutation, instead exhibiting [...] characterized by extensive genomic rearrangements and copy-number changes.
Undifferentiated pleomorphic sarcoma. Circos plot illustrating the complex copy-number and rearrangement patterns seen in a typical undifferentiated pleomorphic sarcoma genome. The outer ring denotes chromosomal location, with subsequent rings representing single-nucleotide variants, insertions, deletions, and copy-number gains and losses. The arcs represent interchromosomal and intrachromosomal rearrangements.
A: complex genetic aberrations
Back Extra: Undifferentiated Sarcoma
- Clinical: Undifferentiated sarcomas often present with a rapidly growing mass, and are found in various anatomical locations with no sex predilection.
- Micro: Pleomorphic undifferentiated sarcomas are characterized by a high mitotic rate, atypical mitoses, and a lack of specific differentiation.
- Ancillary: Undifferentiated pleomorphic sarcomas exhibit complex genetic aberrations with extensive genomic rearrangements and copy-number changes.
Reference Gallery:
Undifferentiated pleomorphic sarcoma. Circos plot illustrating the complex copy-number and rearrangement patterns seen in a typical undifferentiated pleomorphic sarcoma genome. The outer ring denotes chromosomal location, with subsequent rings representing single-nucleotide variants, insertions, deletions, and copy-number gains and losses. The arcs represent interchromosomal and intrachromosomal rearrangements.
Undifferentiated pleomorphic sarcoma. Grossly, undifferentiated pleomorphic sarcomas most often feature a fleshy appearance with areas of necrosis and haemorrhage.
Undifferentiated pleomorphic sarcoma. Undifferentiated pleomorphic sarcoma is composed of a spindle cell and pleomorphic cell population most often characterized by high mitotic activity. Atypical mitoses are very common.
Undifferentiated spindle cell sarcoma. Undifferentiated spindle cell sarcoma features a highly atypical spindle cell proliferation. Mitotic activity is most often high.
Undifferentiated round cell sarcoma. Currently, undifferentiated round cell sarcoma can be diagnosed only if distinctive gene fusions have been ruled out.
Undifferentiated epithelioid sarcoma. Undifferentiated epithelioid sarcoma is most often composed of a high-grade epithelioid cell population lacking any specific line of differentiation.

Q: Grossly, Undifferentiated Sarcoma typically presents as a rapidly growing, fleshy tumor mass frequently displaying prominent areas of necrosis and [...].
Undifferentiated pleomorphic sarcoma. Grossly, undifferentiated pleomorphic sarcomas most often feature a fleshy appearance with areas of necrosis and haemorrhage.
A: hemorrhage
Back Extra: Undifferentiated Sarcoma
- Clinical: Undifferentiated sarcomas often present with a rapidly growing mass, and are found in various anatomical locations with no sex predilection.
- Micro: Pleomorphic undifferentiated sarcomas are characterized by a high mitotic rate, atypical mitoses, and a lack of specific differentiation.
- Ancillary: Undifferentiated pleomorphic sarcomas exhibit complex genetic aberrations with extensive genomic rearrangements and copy-number changes.
Reference Gallery:
Undifferentiated pleomorphic sarcoma. Circos plot illustrating the complex copy-number and rearrangement patterns seen in a typical undifferentiated pleomorphic sarcoma genome. The outer ring denotes chromosomal location, with subsequent rings representing single-nucleotide variants, insertions, deletions, and copy-number gains and losses. The arcs represent interchromosomal and intrachromosomal rearrangements.
Undifferentiated pleomorphic sarcoma. Grossly, undifferentiated pleomorphic sarcomas most often feature a fleshy appearance with areas of necrosis and haemorrhage.
Undifferentiated pleomorphic sarcoma. Undifferentiated pleomorphic sarcoma is composed of a spindle cell and pleomorphic cell population most often characterized by high mitotic activity. Atypical mitoses are very common.
Undifferentiated spindle cell sarcoma. Undifferentiated spindle cell sarcoma features a highly atypical spindle cell proliferation. Mitotic activity is most often high.
Undifferentiated round cell sarcoma. Currently, undifferentiated round cell sarcoma can be diagnosed only if distinctive gene fusions have been ruled out.
Undifferentiated epithelioid sarcoma. Undifferentiated epithelioid sarcoma is most often composed of a high-grade epithelioid cell population lacking any specific line of differentiation.

Q: In Sarcoma with BCOR genetic alterations, the primitive round to ovoid tumor cells characteristically show strong and diffuse nuclear expression of [...] on immunohistochemistry.
Sarcoma with BCOR-CCNB3 fusion. Solid sheets of undifferentiated round to ovoid cells with light eosinophilic to clear cytoplasm and round nuclei with fine chromatin and scattered mitotic figures.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Strong and diffuse nuclear staining for BCOR with immunohistochemistry.
A: BCOR
Back Extra: Sarcoma with BCOR genetic alterations
- Clinical: Sarcoma with BCOR genetic alterations typically presents with pain and swelling, and is more common in children, particularly those under 20 years with BCOR-CCNB3 fusion and infants with BCOR-ITD.
- Micro: BCOR-CCNB3 sarcomas are characterized by solid sheets of primitive round to ovoid cells with finely dispersed chromatin and variable mitotic activity, while BCOR-ITD tumours show variable cellularity and a myxoid matrix.
- Ancillary: Immunohistochemistry shows strong and diffuse nuclear BCOR positivity, and in most cases, SATB2, TLE1, and cyclin D1 are also expressed. BCOR-CCNB3 sarcomas specifically express cyclin B3.
Reference Gallery:
Sarcoma with BCOR-CCNB3 fusion. A primitive round to spindle cell proliferation arranged in sheets and vague fascicles, involving the marrow spaces of a long bone.
Sarcoma with BCOR-CCNB3 fusion. Tumour of lower cellularity embedded in a loose fibromyxoid stroma and microcystic changes.
Sarcoma with BCOR-CCNB3 fusion. Solid sheets of undifferentiated round to ovoid cells with light eosinophilic to clear cytoplasm and round nuclei with fine chromatin and scattered mitotic figures.
Sarcoma with BCOR-CCNB3 fusion. Deceptively bland ovoid to short spindle cells arranged in a streaming pattern in a fibrotic background with a rich vascular network.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Solid sheets of monomorphic round cells with scant eosinophilic cytoplasm and round nuclei, separated by thin septa with delicate capillaries, from an infant patient.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Strong and diffuse nuclear staining for BCOR with immunohistochemistry.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Strong nuclear reactivity for SATB2.
Sarcomas with BCOR genetic alterations. Diagrammatic representation of BCOR genetic abnormalities, including the more common BCOR-CCNB3 intrachromosomal inversion, the rare BCOR-MAML2 interchromosomal fusion, and the BCOR internal tandem duplication (BCOR-ITD). All three of these genetic events involve the last exon (exon 15) of BCOR and result in consistent upregulation of BCOR mRNA and BCOR overexpression at the protein level.

Q: Alongside the defining diagnostic marker, Sarcoma with BCOR genetic alterations often demonstrates strong nuclear reactivity for the marker [...] by immunohistochemistry.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Strong nuclear reactivity for SATB2.
A: SATB2
Back Extra: Sarcoma with BCOR genetic alterations
- Clinical: Sarcoma with BCOR genetic alterations typically presents with pain and swelling, and is more common in children, particularly those under 20 years with BCOR-CCNB3 fusion and infants with BCOR-ITD.
- Micro: BCOR-CCNB3 sarcomas are characterized by solid sheets of primitive round to ovoid cells with finely dispersed chromatin and variable mitotic activity, while BCOR-ITD tumours show variable cellularity and a myxoid matrix.
- Ancillary: Immunohistochemistry shows strong and diffuse nuclear BCOR positivity, and in most cases, SATB2, TLE1, and cyclin D1 are also expressed. BCOR-CCNB3 sarcomas specifically express cyclin B3.
Reference Gallery:
Sarcoma with BCOR-CCNB3 fusion. A primitive round to spindle cell proliferation arranged in sheets and vague fascicles, involving the marrow spaces of a long bone.
Sarcoma with BCOR-CCNB3 fusion. Tumour of lower cellularity embedded in a loose fibromyxoid stroma and microcystic changes.
Sarcoma with BCOR-CCNB3 fusion. Solid sheets of undifferentiated round to ovoid cells with light eosinophilic to clear cytoplasm and round nuclei with fine chromatin and scattered mitotic figures.
Sarcoma with BCOR-CCNB3 fusion. Deceptively bland ovoid to short spindle cells arranged in a streaming pattern in a fibrotic background with a rich vascular network.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Solid sheets of monomorphic round cells with scant eosinophilic cytoplasm and round nuclei, separated by thin septa with delicate capillaries, from an infant patient.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Strong and diffuse nuclear staining for BCOR with immunohistochemistry.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Strong nuclear reactivity for SATB2.
Sarcomas with BCOR genetic alterations. Diagrammatic representation of BCOR genetic abnormalities, including the more common BCOR-CCNB3 intrachromosomal inversion, the rare BCOR-MAML2 interchromosomal fusion, and the BCOR internal tandem duplication (BCOR-ITD). All three of these genetic events involve the last exon (exon 15) of BCOR and result in consistent upregulation of BCOR mRNA and BCOR overexpression at the protein level.

Q: The molecular subtypes of Sarcoma with BCOR genetic alterations correlate with patient age; while BCOR-CCNB3 fusions usually occur in children and young adults, [...] classically present as round cell tumors in infants.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Solid sheets of monomorphic round cells with scant eosinophilic cytoplasm and round nuclei, separated by thin septa with delicate capillaries, from an infant patient.
Sarcomas with BCOR genetic alterations. Diagrammatic representation of BCOR genetic abnormalities, including the more common BCOR-CCNB3 intrachromosomal inversion, the rare BCOR-MAML2 interchromosomal fusion, and the BCOR internal tandem duplication (BCOR-ITD). All three of these genetic events involve the last exon (exon 15) of BCOR and result in consistent upregulation of BCOR mRNA and BCOR overexpression at the protein level.
A: BCOR-ITD (internal tandem duplications)
Back Extra: Sarcoma with BCOR genetic alterations
- Clinical: Sarcoma with BCOR genetic alterations typically presents with pain and swelling, and is more common in children, particularly those under 20 years with BCOR-CCNB3 fusion and infants with BCOR-ITD.
- Micro: BCOR-CCNB3 sarcomas are characterized by solid sheets of primitive round to ovoid cells with finely dispersed chromatin and variable mitotic activity, while BCOR-ITD tumours show variable cellularity and a myxoid matrix.
- Ancillary: Immunohistochemistry shows strong and diffuse nuclear BCOR positivity, and in most cases, SATB2, TLE1, and cyclin D1 are also expressed. BCOR-CCNB3 sarcomas specifically express cyclin B3.
Reference Gallery:
Sarcoma with BCOR-CCNB3 fusion. A primitive round to spindle cell proliferation arranged in sheets and vague fascicles, involving the marrow spaces of a long bone.
Sarcoma with BCOR-CCNB3 fusion. Tumour of lower cellularity embedded in a loose fibromyxoid stroma and microcystic changes.
Sarcoma with BCOR-CCNB3 fusion. Solid sheets of undifferentiated round to ovoid cells with light eosinophilic to clear cytoplasm and round nuclei with fine chromatin and scattered mitotic figures.
Sarcoma with BCOR-CCNB3 fusion. Deceptively bland ovoid to short spindle cells arranged in a streaming pattern in a fibrotic background with a rich vascular network.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Solid sheets of monomorphic round cells with scant eosinophilic cytoplasm and round nuclei, separated by thin septa with delicate capillaries, from an infant patient.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Strong and diffuse nuclear staining for BCOR with immunohistochemistry.
Sarcoma with BCOR internal tandem duplication (BCOR-ITD). Strong nuclear reactivity for SATB2.
Sarcomas with BCOR genetic alterations. Diagrammatic representation of BCOR genetic abnormalities, including the more common BCOR-CCNB3 intrachromosomal inversion, the rare BCOR-MAML2 interchromosomal fusion, and the BCOR internal tandem duplication (BCOR-ITD). All three of these genetic events involve the last exon (exon 15) of BCOR and result in consistent upregulation of BCOR mRNA and BCOR overexpression at the protein level.

Q: Histologically, CIC-rearranged sarcoma typically presents as an undifferentiated [...] tumor with a lobular growth pattern and mild nuclear pleomorphism.
CIC-DUX4 sarcoma. This sarcoma shows a lobular growth pattern divided by fibrous septa.
CIC-DUX4 sarcoma. High power showing solid sheets of primitive round cells with scattered larger cells and mild nuclear pleomorphism.
A: round cell
Back Extra: CIC-rearranged sarcoma
- Clinical: CIC-rearranged sarcoma presents as a mass with or without pain, commonly in young adults (median age: 25–35 years) with a slight male predominance.
- Micro: The tumour is composed of diffuse sheets of undifferentiated round cells with a lobular growth pattern, mild nuclear pleomorphism, and frequent necrosis.
- Ancillary: Immunohistochemistry shows consistent strong nuclear staining for WT1 (90–95%) and ETV4 (95–100%), which are key markers for diagnosing CIC-rearranged sarcoma.
Reference Gallery:
CIC-DUX4 sarcoma. This sarcoma shows a lobular growth pattern divided by fibrous septa.
CIC-DUX4 sarcoma. High power showing solid sheets of primitive round cells with scattered larger cells and mild nuclear pleomorphism.
CIC-DUX4 sarcoma. Solid sheets composed of relatively monomorphic epithelioid cells with moderate amount of light eosinophilic to clear cytoplasm.
CIC-DUX4 sarcoma. Focal areas of short spindle cells arranged in a storiform pattern.
CIC-DUX4 sarcoma. Immunohistochemical studies show consistent strong nuclear staining for WT1.
CIC-DUX4 sarcoma. Diffuse nuclear staining for ETV4.
CIC-DUX4 sarcoma. Diagrammatic representation of CIC-DUX4 fusions, which result from either a t(4;19) or a t(10;19) translocation. The interrupted red line highlights the common breakpoints, which include most of the coding sequence of CIC and a small portion of the 3′ end of DUX4. The resulting fusion protein drives the oncogenic activation of target genes, such as the PEA3 family of transcription factors (ETV1, ETV4).

Q: In CIC-rearranged sarcoma, immunohistochemistry classically demonstrates consistent, strong nuclear positivity for WT1 and [...].
CIC-DUX4 sarcoma. Immunohistochemical studies show consistent strong nuclear staining for WT1.
CIC-DUX4 sarcoma. Diffuse nuclear staining for ETV4.
A: ETV4
Back Extra: CIC-rearranged sarcoma
- Clinical: CIC-rearranged sarcoma presents as a mass with or without pain, commonly in young adults (median age: 25–35 years) with a slight male predominance.
- Micro: The tumour is composed of diffuse sheets of undifferentiated round cells with a lobular growth pattern, mild nuclear pleomorphism, and frequent necrosis.
- Ancillary: Immunohistochemistry shows consistent strong nuclear staining for WT1 (90–95%) and ETV4 (95–100%), which are key markers for diagnosing CIC-rearranged sarcoma.
Reference Gallery:
CIC-DUX4 sarcoma. This sarcoma shows a lobular growth pattern divided by fibrous septa.
CIC-DUX4 sarcoma. High power showing solid sheets of primitive round cells with scattered larger cells and mild nuclear pleomorphism.
CIC-DUX4 sarcoma. Solid sheets composed of relatively monomorphic epithelioid cells with moderate amount of light eosinophilic to clear cytoplasm.
CIC-DUX4 sarcoma. Focal areas of short spindle cells arranged in a storiform pattern.
CIC-DUX4 sarcoma. Immunohistochemical studies show consistent strong nuclear staining for WT1.
CIC-DUX4 sarcoma. Diffuse nuclear staining for ETV4.
CIC-DUX4 sarcoma. Diagrammatic representation of CIC-DUX4 fusions, which result from either a t(4;19) or a t(10;19) translocation. The interrupted red line highlights the common breakpoints, which include most of the coding sequence of CIC and a small portion of the 3′ end of DUX4. The resulting fusion protein drives the oncogenic activation of target genes, such as the PEA3 family of transcription factors (ETV1, ETV4).

Q: CIC-rearranged sarcoma is most commonly driven by a gene fusion involving CIC and DUX4, typically resulting from the translocations t(10;19) or [...].
CIC-DUX4 sarcoma. Diagrammatic representation of CIC-DUX4 fusions, which result from either a t(4;19) or a t(10;19) translocation. The interrupted red line highlights the common breakpoints, which include most of the coding sequence of CIC and a small portion of the 3′ end of DUX4. The resulting fusion protein drives the oncogenic activation of target genes, such as the PEA3 family of transcription factors (ETV1, ETV4).
A: t(4;19)
Back Extra: CIC-rearranged sarcoma
- Clinical: CIC-rearranged sarcoma presents as a mass with or without pain, commonly in young adults (median age: 25–35 years) with a slight male predominance.
- Micro: The tumour is composed of diffuse sheets of undifferentiated round cells with a lobular growth pattern, mild nuclear pleomorphism, and frequent necrosis.
- Ancillary: Immunohistochemistry shows consistent strong nuclear staining for WT1 (90–95%) and ETV4 (95–100%), which are key markers for diagnosing CIC-rearranged sarcoma.
Reference Gallery:
CIC-DUX4 sarcoma. This sarcoma shows a lobular growth pattern divided by fibrous septa.
CIC-DUX4 sarcoma. High power showing solid sheets of primitive round cells with scattered larger cells and mild nuclear pleomorphism.
CIC-DUX4 sarcoma. Solid sheets composed of relatively monomorphic epithelioid cells with moderate amount of light eosinophilic to clear cytoplasm.
CIC-DUX4 sarcoma. Focal areas of short spindle cells arranged in a storiform pattern.
CIC-DUX4 sarcoma. Immunohistochemical studies show consistent strong nuclear staining for WT1.
CIC-DUX4 sarcoma. Diffuse nuclear staining for ETV4.
CIC-DUX4 sarcoma. Diagrammatic representation of CIC-DUX4 fusions, which result from either a t(4;19) or a t(10;19) translocation. The interrupted red line highlights the common breakpoints, which include most of the coding sequence of CIC and a small portion of the 3′ end of DUX4. The resulting fusion protein drives the oncogenic activation of target genes, such as the PEA3 family of transcription factors (ETV1, ETV4).

Q: A characteristic histologic finding in Anastomosing Haemangioma is the frequent presence of extramedullary [...], seen dispersed among the capillary-sized vessels.
Anastomosing haemangioma. The lesion is composed of vascular spaces that are cuffed by supporting cells. Note the extramedullary haematopoiesis (erythropoiesis) in the upper-central part of the image.
Anastomosing haemangioma. Both hyaline globules and a megakaryocyte are seen.
A: hematopoiesis
Q: Anastomosing Haemangioma
- Clinical: Anastomosing haemangiomas are often incidental findings on imaging studies, but renal lesions can present with haematuria and hepatic lesions can be large and infiltrative.
- Micro: The lesion is characterized by anastomosing sinusoidal capillary-sized vessels with scattered hobnail endothelial cells, and extramedullary haematopoiesis is a common feature.
- Ancillary: Activating hotspot mutations in [...] are commonly found in anastomosing haemangiomas.
Reference Gallery:
Anastomosing haemangioma. The lesion is well marginated, which is generally the case.
Anastomosing haemangioma. This renal lesion is rather sclerotic and infiltrated the renal pelvic adipose tissue. However, note that the tumour is arranged in lobules.
Anastomosing haemangioma. The lesion is composed of vascular spaces that are cuffed by supporting cells. Note the extramedullary haematopoiesis (erythropoiesis) in the upper-central part of the image.
Anastomosing haemangioma. Note the anastomosing growth pattern and tiny hobnail endothelial cells.
Anastomosing haemangioma. Both hyaline globules and a megakaryocyte are seen.
A: GNAQ or GNA14

Q: Microscopically, Anastomosing Haemangioma features an anastomosing network of sinusoidal vascular channels lined by scattered endothelial cells with a distinctive [...] morphology.
Anastomosing haemangioma. Note the anastomosing growth pattern and tiny hobnail endothelial cells.
A: hobnail
Q: Anastomosing Haemangioma
- Clinical: Anastomosing haemangiomas are often incidental findings on imaging studies, but renal lesions can present with haematuria and hepatic lesions can be large and infiltrative.
- Micro: The lesion is characterized by anastomosing sinusoidal capillary-sized vessels with scattered hobnail endothelial cells, and extramedullary haematopoiesis is a common feature.
- Ancillary: Activating hotspot mutations in [...] are commonly found in anastomosing haemangiomas.
Reference Gallery:
Anastomosing haemangioma. The lesion is well marginated, which is generally the case.
Anastomosing haemangioma. This renal lesion is rather sclerotic and infiltrated the renal pelvic adipose tissue. However, note that the tumour is arranged in lobules.
Anastomosing haemangioma. The lesion is composed of vascular spaces that are cuffed by supporting cells. Note the extramedullary haematopoiesis (erythropoiesis) in the upper-central part of the image.
Anastomosing haemangioma. Note the anastomosing growth pattern and tiny hobnail endothelial cells.
Anastomosing haemangioma. Both hyaline globules and a megakaryocyte are seen.
A: GNAQ or GNA14

Q: Microscopically, Epithelioid Haemangioma is characterized by blood vessels lined by plump endothelial cells; a classic variant also features a heavy inflammatory infiltrate rich in [...] (historically termed angiolymphoid hyperplasia with eosinophilia).
Epithelioid haemangioma. High-power view details the endothelial cells, which have glassy and eosinophilic cytoplasm and central enlarged nuclei with prominent nucleoli.
Epithelioid haemangioma. Well-formed vessels with abundant eosinophilic infiltration in angiolymphoid hyperplasia with eosinophilia–type epithelioid haemangioma.
A: eosinophils
Back Extra: Epithelioid Haemangioma
- Clinical: Epithelioid haemangioma typically presents as a single cutaneous erythematous-violaceous papule or nodule, with a peak incidence in the fourth decade of life.
- Micro: The lesion shows a proliferation of well-formed small blood vessels lined by plump, epithelioid endothelial cells with abundant eosinophilic cytoplasm and enlarged nuclei.
- Ancillary: Immunohistochemically, the tumour cells are positive for endothelial markers such as CD31, FLI1, and ERG, and many cases show rearrangement of the FOS or FOSB gene.
Reference Gallery:
Epithelioid haemangioma. Epithelioid haemangioma shows a multilobular growth pattern.
Epithelioid haemangioma. High-power view details the endothelial cells, which have glassy and eosinophilic cytoplasm and central enlarged nuclei with prominent nucleoli.
Epithelioid haemangioma. Exuberant or cellular examples of epithelioid haemangioma exhibit high cellularity and sheet-like areas with inconspicuous or slit-like vascular lumina and scant intervening stroma. These lesions usually have a conventional vasoformative pattern and peripheral maturation.
Epithelioid haemangioma. Histological variations: this lesion is confined within a large vein, indicating intravascular growth of epithelioid haemangioma.
Epithelioid haemangioma. Well-formed vessels with abundant eosinophilic infiltration in angiolymphoid hyperplasia with eosinophilia–type epithelioid haemangioma.
Epithelioid haemangioma. Compact proliferation of epithelioid endothelial cells in an exuberant example of penile epithelioid haemangioma.
Epithelioid haemangioma. There is strong nuclear staining for FOSB in this cellular example of epithelioid haemangioma.

Q: A notable histologic variation of Epithelioid Haemangioma is its tendency for [...] growth, where the lobular vascular proliferation is confined within the lumen of a large vein.
Epithelioid haemangioma. Histological variations: this lesion is confined within a large vein, indicating intravascular growth of epithelioid haemangioma.
A: intravascular
Back Extra: Epithelioid Haemangioma
- Clinical: Epithelioid haemangioma typically presents as a single cutaneous erythematous-violaceous papule or nodule, with a peak incidence in the fourth decade of life.
- Micro: The lesion shows a proliferation of well-formed small blood vessels lined by plump, epithelioid endothelial cells with abundant eosinophilic cytoplasm and enlarged nuclei.
- Ancillary: Immunohistochemically, the tumour cells are positive for endothelial markers such as CD31, FLI1, and ERG, and many cases show rearrangement of the FOS or FOSB gene.
Reference Gallery:
Epithelioid haemangioma. Epithelioid haemangioma shows a multilobular growth pattern.
Epithelioid haemangioma. High-power view details the endothelial cells, which have glassy and eosinophilic cytoplasm and central enlarged nuclei with prominent nucleoli.
Epithelioid haemangioma. Exuberant or cellular examples of epithelioid haemangioma exhibit high cellularity and sheet-like areas with inconspicuous or slit-like vascular lumina and scant intervening stroma. These lesions usually have a conventional vasoformative pattern and peripheral maturation.
Epithelioid haemangioma. Histological variations: this lesion is confined within a large vein, indicating intravascular growth of epithelioid haemangioma.
Epithelioid haemangioma. Well-formed vessels with abundant eosinophilic infiltration in angiolymphoid hyperplasia with eosinophilia–type epithelioid haemangioma.
Epithelioid haemangioma. Compact proliferation of epithelioid endothelial cells in an exuberant example of penile epithelioid haemangioma.
Epithelioid haemangioma. There is strong nuclear staining for FOSB in this cellular example of epithelioid haemangioma.

Q: Immunohistochemically, a subset of Epithelioid Haemangioma cases show strong nuclear expression of [...], corresponding to recurrent genetic rearrangements driving the tumor.
Epithelioid haemangioma. There is strong nuclear staining for FOSB in this cellular example of epithelioid haemangioma.
A: FOSB
Back Extra: Epithelioid Haemangioma
- Clinical: Epithelioid haemangioma typically presents as a single cutaneous erythematous-violaceous papule or nodule, with a peak incidence in the fourth decade of life.
- Micro: The lesion shows a proliferation of well-formed small blood vessels lined by plump, epithelioid endothelial cells with abundant eosinophilic cytoplasm and enlarged nuclei.
- Ancillary: Immunohistochemically, the tumour cells are positive for endothelial markers such as CD31, FLI1, and ERG, and many cases show rearrangement of the FOS or FOSB gene.
Reference Gallery:
Epithelioid haemangioma. Epithelioid haemangioma shows a multilobular growth pattern.
Epithelioid haemangioma. High-power view details the endothelial cells, which have glassy and eosinophilic cytoplasm and central enlarged nuclei with prominent nucleoli.
Epithelioid haemangioma. Exuberant or cellular examples of epithelioid haemangioma exhibit high cellularity and sheet-like areas with inconspicuous or slit-like vascular lumina and scant intervening stroma. These lesions usually have a conventional vasoformative pattern and peripheral maturation.
Epithelioid haemangioma. Histological variations: this lesion is confined within a large vein, indicating intravascular growth of epithelioid haemangioma.
Epithelioid haemangioma. Well-formed vessels with abundant eosinophilic infiltration in angiolymphoid hyperplasia with eosinophilia–type epithelioid haemangioma.
Epithelioid haemangioma. Compact proliferation of epithelioid endothelial cells in an exuberant example of penile epithelioid haemangioma.
Epithelioid haemangioma. There is strong nuclear staining for FOSB in this cellular example of epithelioid haemangioma.

Q: A striking histologic feature of Intramuscular Angioma is the extensive replacement of skeletal muscle by mixed vascular channels, intricately admixed with prominent, mature [...].
Intramuscular angioma. Extensive replacement of the muscle by dilated vascular channels with focal thrombosis. There is a prominent adipocytic component.
Intramuscular angioma. Extensive adipocytic component with muscle atrophy.
A: adipose tissue
Back Extra: Intramuscular Angioma
- Clinical: Intramuscular angiomas typically present as slow-growing, painful masses, especially after exercise, and are often located in the limbs.
- Micro: These tumors are characterized by a mixture of vessel types, including lymphatics, veins, cavernous-like spaces, and capillaries, along with variable amounts of mature adipose tissue and muscle atrophy.
- Ancillary: MRI is the most important radiological technique for diagnosis, often revealing calcification due to phleboliths or metaplastic ossification.
Reference Gallery:
Intramuscular angioma. This lesion was excised from the rectus abdominis muscle of a young woman. Note the poorly circumscribed margins and prominent fatty stroma.
Intramuscular angioma. Extensive replacement of the muscle by dilated vascular channels with focal thrombosis. There is a prominent adipocytic component.
Intramuscular angioma. Predominance of cavernous-like vascular spaces.
Intramuscular angioma. Extensive adipocytic component with muscle atrophy.
Intramuscular angioma. Entrapped muscle fibres with hyperchromatic, reactive nuclei.

Q: A poorly circumscribed, deeply seated soft tissue lesion featuring cavernous-like vascular spaces that infiltrate skeletal muscle, causing muscle fiber atrophy and entrapping fibers with reactive nuclei, is diagnostic of a(n) [...].
Intramuscular angioma. Predominance of cavernous-like vascular spaces.
Intramuscular angioma. Entrapped muscle fibres with hyperchromatic, reactive nuclei.
A: Intramuscular Angioma
Back Extra: Intramuscular Angioma
- Clinical: Intramuscular angiomas typically present as slow-growing, painful masses, especially after exercise, and are often located in the limbs.
- Micro: These tumors are characterized by a mixture of vessel types, including lymphatics, veins, cavernous-like spaces, and capillaries, along with variable amounts of mature adipose tissue and muscle atrophy.
- Ancillary: MRI is the most important radiological technique for diagnosis, often revealing calcification due to phleboliths or metaplastic ossification.
Reference Gallery:
Intramuscular angioma. This lesion was excised from the rectus abdominis muscle of a young woman. Note the poorly circumscribed margins and prominent fatty stroma.
Intramuscular angioma. Extensive replacement of the muscle by dilated vascular channels with focal thrombosis. There is a prominent adipocytic component.
Intramuscular angioma. Predominance of cavernous-like vascular spaces.
Intramuscular angioma. Extensive adipocytic component with muscle atrophy.
Intramuscular angioma. Entrapped muscle fibres with hyperchromatic, reactive nuclei.

Q: Histologically, Synovial Haemangioma is characterized by a proliferation of mixed capillary and [...] vascular channels underlying the synovium, frequently accompanied by hemosiderin deposition and villous hyperplasia.
Synovial haemangioma. A mixture of cavernous and capillary vascular channels underlies the synovium.
A: cavernous
Back Extra: Synovial Haemangioma
- Clinical: Synovial haemangioma presents as a slow-growing lesion with swelling, joint effusion, and recurrent pain. Rarely, it can cause destructive growth and bone involvement.
- Micro: The lesion is characterized by numerous congested, variably dilated vessels, often with a cavernous appearance. Haemosiderin deposition and villous hyperplasia of the synovium may be present.
- Ancillary: MRI is the best radiological technique for diagnosing synovial haemangioma and determining its extent.
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Synovial haemangioma. A mixture of cavernous and capillary vascular channels underlies the synovium.

Q: Microscopically, Venous Haemangioma is a vascular tumor defined by the presence of large, variably dilated vessels that typically possess [...].
Venous haemangioma. Venous haemangioma with typically numerous prominent thick-walled veins.
A: thick muscular walls
Back Extra: Venous Haemangioma
- Clinical: Venous haemangioma often presents as a longstanding slow-growing tumour, with radiological examination commonly showing the presence of calcification due to phleboliths.
- Micro: The lesion typically consists of large thick-walled muscular vessels, which are variably dilated and commonly display thrombosis, with occasional formation of phleboliths.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of venous haemangioma.
Reference Gallery:
Venous haemangioma. Venous haemangioma with typically numerous prominent thick-walled veins.

Q: A longstanding vascular tumor characterized by large, variably dilated vessels with thick muscular walls and the frequent formation of intravascular calcifications (phleboliths) is most likely a [...].
Venous haemangioma. Venous haemangioma with typically numerous prominent thick-walled veins.
A: Venous Haemangioma
Back Extra: Venous Haemangioma
- Clinical: Venous haemangioma often presents as a longstanding slow-growing tumour, with radiological examination commonly showing the presence of calcification due to phleboliths.
- Micro: The lesion typically consists of large thick-walled muscular vessels, which are variably dilated and commonly display thrombosis, with occasional formation of phleboliths.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of venous haemangioma.
Reference Gallery:
Venous haemangioma. Venous haemangioma with typically numerous prominent thick-walled veins.

Q: The characteristic microscopic appearance of Lymphangioma and Lymphangiomatosis features variably sized, thin-walled, and markedly dilated [...] lined by a bland, flattened endothelium.
Lymphangioma of the mesentery. Showing multiple, markedly ectatic lymphatic channels containing lymph and lined by small bland endothelial cells.
Lymphangioma of the mesentery. Present within the bowel muscularis propria, this lymphangioma shows well-formed, dilated lymphatic channels that contain lymphocytes and are lined by flattened endothelial cells lacking any atypia.
A: lymphatic channels
Back Extra: Lymphangioma and Lymphangiomatosis
- Clinical: Lymphangiomas appear as pale or pink vesicles on the skin, and deeper lesions present as soft, fluctuant, painless swellings. They can cause compression of surrounding organs, leading to issues such as tracheal and esophageal compression or intestinal obstruction.
- Micro: Cavernous lymphangiomas contain variably sized, thin-walled, dilated lymphatic vessels lined by flattened endothelium, often surrounded by lymphocytic aggregates. Larger vessels may have a smooth muscle layer and show interstitial fibrosis and stromal inflammation.
- Ancillary: Immunohistochemical stains for CD31 and D2-40 are consistently positive in lymphangiomas, while CD34 expression is variable. Smooth muscle actin (SMA) is positive in the smooth muscle cells surrounding the cysts.
Reference Gallery:
Lymphangioma. Lymphangioma of the small intestine involving mucosa and submucosa. The lymphatic channels are dilated and lined by inconspicuous endothelium, and they contain lymphatic fluid and occasional lipid-laden macrophages.
Lymphangioma of the mesentery. Showing multiple, markedly ectatic lymphatic channels containing lymph and lined by small bland endothelial cells.
Lymphangioma of the mesentery. Present within the bowel muscularis propria, this lymphangioma shows well-formed, dilated lymphatic channels that contain lymphocytes and are lined by flattened endothelial cells lacking any atypia.
Lymphangiomatosis, mucosal. This example of lymphangiomatosis is seen within bowel mucosa. The ectatic lymphatic channels are lined by small, almost imperceptible spindle cells and contain prominent cloudy lymph as well as numerous lymphocytes.

Q: Unlike hemangiomas, which are typically filled with red blood cells, the ectatic vessels of Lymphangioma and Lymphangiomatosis characteristically contain cloudy fluid, lipid-laden macrophages, and numerous [...].
Lymphangioma. Lymphangioma of the small intestine involving mucosa and submucosa. The lymphatic channels are dilated and lined by inconspicuous endothelium, and they contain lymphatic fluid and occasional lipid-laden macrophages.
Lymphangiomatosis, mucosal. This example of lymphangiomatosis is seen within bowel mucosa. The ectatic lymphatic channels are lined by small, almost imperceptible spindle cells and contain prominent cloudy lymph as well as numerous lymphocytes.
A: lymphocytes
Back Extra: Lymphangioma and Lymphangiomatosis
- Clinical: Lymphangiomas appear as pale or pink vesicles on the skin, and deeper lesions present as soft, fluctuant, painless swellings. They can cause compression of surrounding organs, leading to issues such as tracheal and esophageal compression or intestinal obstruction.
- Micro: Cavernous lymphangiomas contain variably sized, thin-walled, dilated lymphatic vessels lined by flattened endothelium, often surrounded by lymphocytic aggregates. Larger vessels may have a smooth muscle layer and show interstitial fibrosis and stromal inflammation.
- Ancillary: Immunohistochemical stains for CD31 and D2-40 are consistently positive in lymphangiomas, while CD34 expression is variable. Smooth muscle actin (SMA) is positive in the smooth muscle cells surrounding the cysts.
Reference Gallery:
Lymphangioma. Lymphangioma of the small intestine involving mucosa and submucosa. The lymphatic channels are dilated and lined by inconspicuous endothelium, and they contain lymphatic fluid and occasional lipid-laden macrophages.
Lymphangioma of the mesentery. Showing multiple, markedly ectatic lymphatic channels containing lymph and lined by small bland endothelial cells.
Lymphangioma of the mesentery. Present within the bowel muscularis propria, this lymphangioma shows well-formed, dilated lymphatic channels that contain lymphocytes and are lined by flattened endothelial cells lacking any atypia.
Lymphangiomatosis, mucosal. This example of lymphangiomatosis is seen within bowel mucosa. The ectatic lymphatic channels are lined by small, almost imperceptible spindle cells and contain prominent cloudy lymph as well as numerous lymphocytes.

Q: The histologic hallmark of Composite Haemangioendothelioma is a poorly circumscribed, infiltrative tumor containing an admixture of multiple vascular components, typically including epithelioid and [...] hemangioendothelioma-like areas.
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like area composed of sheets of epithelioid cells with occasionally prominent cytoplasmic vacuolization.
Composite haemangioendothelioma. Retiform haemangioendothelioma–like area composed of anastomosing vascular channels lined by hobnailing endothelium with an appearance reminiscent of rete testis.
A: retiform
Back Extra: Composite Haemangioendothelioma
- Clinical: Composite Haemangioendothelioma often presents as a reddish-blue, multinodular mass, commonly found on the distal extremities or head and neck.
- Micro: The lesion is poorly circumscribed and infiltrative, containing a mix of histologically benign and malignant vascular components, including epithelioid haemangioendothelioma and retiform haemangioendothelioma-like areas.
- Ancillary: Positive for CD31, ERG, and FLI1; some cases may show neuroendocrine marker expression (e.g., synaptophysin).
Reference Gallery:
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like area composed of sheets of epithelioid cells with occasionally prominent cytoplasmic vacuolization.
Composite haemangioendothelioma. Haemangioma-like area with dilated vascular spaces lined by flat, unremarkable endothelium. Other components of this lesion were epithelioid haemangioendothelioma–like, retiform haemangioendothelioma–like, and epithelioid angiosarcoma–like.
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like component composed of cords and nests of epithelioid cells in a hyalinized stroma.
Neuroendocrine composite haemangioendothelioma. Retiform haemangioendothelioma–like area from a neuroendocrine composite haemangioendothelioma composed of anastomosing vessels lined by hobnailing endothelium with an appearance reminiscent of rete testis.
Composite haemangioendothelioma. Retiform haemangioendothelioma–like area composed of anastomosing vascular channels lined by hobnailing endothelium with an appearance reminiscent of rete testis.
Neuroendocrine composite haemangioendothelioma. Nests of epithelioid cells characteristic of neuroendocrine composite haemangioendothelioma.
Neuroendocrine composite haemangioendothelioma. Neuroendocrine composite haemangioendothelioma showing diffuse and strong immunoreactivity for CD31.
Neuroendocrine composite haemangioendothelioma. Neuroendocrine composite haemangioendothelioma exhibiting diffuse and strong immunoreactivity for synaptophysin.
Composite haemangioendothelioma. An area suggestive of low-grade angiosarcoma composed of irregular vascular structures with a dissecting/infiltrative growth pattern.
Composite haemangioendothelioma. This composite haemangioendothelioma had an area composed of sheets of malignant-appearing epithelioid cells with high mitotic activity, overall with an epithelioid angiosarcoma–like appearance.
Composite haemangioendothelioma. Composite haemangioendothelioma presenting as a bluish-purple multinodular mass.
Composite haemangioendothelioma. Uniform hobnail endothelial cells with round nuclei and fine chromatin lining the vascular spaces.

Q: Grossly, Composite Haemangioendothelioma characteristically presents on the distal extremities or head and neck as a reddish-blue, [...].
Composite haemangioendothelioma. Composite haemangioendothelioma presenting as a bluish-purple multinodular mass.
A: multinodular mass
Back Extra: Composite Haemangioendothelioma
- Clinical: Composite Haemangioendothelioma often presents as a reddish-blue, multinodular mass, commonly found on the distal extremities or head and neck.
- Micro: The lesion is poorly circumscribed and infiltrative, containing a mix of histologically benign and malignant vascular components, including epithelioid haemangioendothelioma and retiform haemangioendothelioma-like areas.
- Ancillary: Positive for CD31, ERG, and FLI1; some cases may show neuroendocrine marker expression (e.g., synaptophysin).
Reference Gallery:
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like area composed of sheets of epithelioid cells with occasionally prominent cytoplasmic vacuolization.
Composite haemangioendothelioma. Haemangioma-like area with dilated vascular spaces lined by flat, unremarkable endothelium. Other components of this lesion were epithelioid haemangioendothelioma–like, retiform haemangioendothelioma–like, and epithelioid angiosarcoma–like.
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like component composed of cords and nests of epithelioid cells in a hyalinized stroma.
Neuroendocrine composite haemangioendothelioma. Retiform haemangioendothelioma–like area from a neuroendocrine composite haemangioendothelioma composed of anastomosing vessels lined by hobnailing endothelium with an appearance reminiscent of rete testis.
Composite haemangioendothelioma. Retiform haemangioendothelioma–like area composed of anastomosing vascular channels lined by hobnailing endothelium with an appearance reminiscent of rete testis.
Neuroendocrine composite haemangioendothelioma. Nests of epithelioid cells characteristic of neuroendocrine composite haemangioendothelioma.
Neuroendocrine composite haemangioendothelioma. Neuroendocrine composite haemangioendothelioma showing diffuse and strong immunoreactivity for CD31.
Neuroendocrine composite haemangioendothelioma. Neuroendocrine composite haemangioendothelioma exhibiting diffuse and strong immunoreactivity for synaptophysin.
Composite haemangioendothelioma. An area suggestive of low-grade angiosarcoma composed of irregular vascular structures with a dissecting/infiltrative growth pattern.
Composite haemangioendothelioma. This composite haemangioendothelioma had an area composed of sheets of malignant-appearing epithelioid cells with high mitotic activity, overall with an epithelioid angiosarcoma–like appearance.
Composite haemangioendothelioma. Composite haemangioendothelioma presenting as a bluish-purple multinodular mass.
Composite haemangioendothelioma. Uniform hobnail endothelial cells with round nuclei and fine chromatin lining the vascular spaces.

Q: While typically expressing vascular markers like CD31, a specific variant of Composite Haemangioendothelioma also shows diffuse and strong immunoreactivity for the neuroendocrine marker [...].
Neuroendocrine composite haemangioendothelioma. Neuroendocrine composite haemangioendothelioma showing diffuse and strong immunoreactivity for CD31.
Neuroendocrine composite haemangioendothelioma. Neuroendocrine composite haemangioendothelioma exhibiting diffuse and strong immunoreactivity for synaptophysin.
A: synaptophysin
Back Extra: Composite Haemangioendothelioma
- Clinical: Composite Haemangioendothelioma often presents as a reddish-blue, multinodular mass, commonly found on the distal extremities or head and neck.
- Micro: The lesion is poorly circumscribed and infiltrative, containing a mix of histologically benign and malignant vascular components, including epithelioid haemangioendothelioma and retiform haemangioendothelioma-like areas.
- Ancillary: Positive for CD31, ERG, and FLI1; some cases may show neuroendocrine marker expression (e.g., synaptophysin).
Reference Gallery:
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like area composed of sheets of epithelioid cells with occasionally prominent cytoplasmic vacuolization.
Composite haemangioendothelioma. Haemangioma-like area with dilated vascular spaces lined by flat, unremarkable endothelium. Other components of this lesion were epithelioid haemangioendothelioma–like, retiform haemangioendothelioma–like, and epithelioid angiosarcoma–like.
Composite haemangioendothelioma. Epithelioid haemangioendothelioma–like component composed of cords and nests of epithelioid cells in a hyalinized stroma.
Neuroendocrine composite haemangioendothelioma. Retiform haemangioendothelioma–like area from a neuroendocrine composite haemangioendothelioma composed of anastomosing vessels lined by hobnailing endothelium with an appearance reminiscent of rete testis.
Composite haemangioendothelioma. Retiform haemangioendothelioma–like area composed of anastomosing vascular channels lined by hobnailing endothelium with an appearance reminiscent of rete testis.
Neuroendocrine composite haemangioendothelioma. Nests of epithelioid cells characteristic of neuroendocrine composite haemangioendothelioma.
Neuroendocrine composite haemangioendothelioma. Neuroendocrine composite haemangioendothelioma showing diffuse and strong immunoreactivity for CD31.
Neuroendocrine composite haemangioendothelioma. Neuroendocrine composite haemangioendothelioma exhibiting diffuse and strong immunoreactivity for synaptophysin.
Composite haemangioendothelioma. An area suggestive of low-grade angiosarcoma composed of irregular vascular structures with a dissecting/infiltrative growth pattern.
Composite haemangioendothelioma. This composite haemangioendothelioma had an area composed of sheets of malignant-appearing epithelioid cells with high mitotic activity, overall with an epithelioid angiosarcoma–like appearance.
Composite haemangioendothelioma. Composite haemangioendothelioma presenting as a bluish-purple multinodular mass.
Composite haemangioendothelioma. Uniform hobnail endothelial cells with round nuclei and fine chromatin lining the vascular spaces.

Q: In the nodular stage of Kaposi sarcoma, the histologic hallmark is a proliferation of mildly atypical spindle cells forming numerous [...] containing extravasated erythrocytes.
Nodular-stage Kaposi sarcoma. This example shows a cellular proliferation comprising fascicles of spindle cells, with prominent surrounding haemorrhage. Numerous small slit-like spaces containing erythrocytes are discernible, even at low power, with small numbers of ectatic vessels.
Nodular-stage Kaposi sarcoma. At higher power, the cells are uniform and contain minimally atypical elongated spindled vesicular nuclei.
A: slit-like spaces
Back Extra: Kaposi Sarcoma
- Clinical: Kaposi sarcoma commonly presents with reddish-purple/dark-brown macules, plaques, and nodules, particularly in distal extremities, and may be accompanied by lymphoedema.
- Micro: Nodular-stage Kaposi sarcoma is characterized by circumscribed nodules of spindle cell fascicles, minimal atypia, hyaline globules, and numerous slit-like spaces containing erythrocytes.
- Ancillary: PCR and in situ hybridization demonstrate HHV8 in the flat endothelial cells lining vascular spaces and in spindle cells, with strong nuclear expression of HHV8.
Reference Gallery:
Nodular-stage Kaposi sarcoma. This example shows a cellular proliferation comprising fascicles of spindle cells, with prominent surrounding haemorrhage. Numerous small slit-like spaces containing erythrocytes are discernible, even at low power, with small numbers of ectatic vessels.
Nodular-stage Kaposi sarcoma. At higher power, the cells are uniform and contain minimally atypical elongated spindled vesicular nuclei.
Kaposi sarcoma. Hyaline globules, which can be intracellular or extracellular, are scattered within this lesion.
Kaposi sarcoma. This example of nodular Kaposi sarcoma shows strong nuclear expression of HHV8 in spindle cells.

Q: A characteristic microscopic finding scattered within the spindle cell fascicles of Kaposi sarcoma is the presence of intra- and extracellular [...].
Kaposi sarcoma. Hyaline globules, which can be intracellular or extracellular, are scattered within this lesion.
A: hyaline globules
Back Extra: Kaposi Sarcoma
- Clinical: Kaposi sarcoma commonly presents with reddish-purple/dark-brown macules, plaques, and nodules, particularly in distal extremities, and may be accompanied by lymphoedema.
- Micro: Nodular-stage Kaposi sarcoma is characterized by circumscribed nodules of spindle cell fascicles, minimal atypia, hyaline globules, and numerous slit-like spaces containing erythrocytes.
- Ancillary: PCR and in situ hybridization demonstrate HHV8 in the flat endothelial cells lining vascular spaces and in spindle cells, with strong nuclear expression of HHV8.
Reference Gallery:
Nodular-stage Kaposi sarcoma. This example shows a cellular proliferation comprising fascicles of spindle cells, with prominent surrounding haemorrhage. Numerous small slit-like spaces containing erythrocytes are discernible, even at low power, with small numbers of ectatic vessels.
Nodular-stage Kaposi sarcoma. At higher power, the cells are uniform and contain minimally atypical elongated spindled vesicular nuclei.
Kaposi sarcoma. Hyaline globules, which can be intracellular or extracellular, are scattered within this lesion.
Kaposi sarcoma. This example of nodular Kaposi sarcoma shows strong nuclear expression of HHV8 in spindle cells.

Q: The diagnosis of Kaposi sarcoma can be confirmed by demonstrating strong nuclear immunohistochemical expression of [...] within the neoplastic spindle and endothelial cells.
Kaposi sarcoma. This example of nodular Kaposi sarcoma shows strong nuclear expression of HHV8 in spindle cells.
A: HHV8
Back Extra: Kaposi Sarcoma
- Clinical: Kaposi sarcoma commonly presents with reddish-purple/dark-brown macules, plaques, and nodules, particularly in distal extremities, and may be accompanied by lymphoedema.
- Micro: Nodular-stage Kaposi sarcoma is characterized by circumscribed nodules of spindle cell fascicles, minimal atypia, hyaline globules, and numerous slit-like spaces containing erythrocytes.
- Ancillary: PCR and in situ hybridization demonstrate HHV8 in the flat endothelial cells lining vascular spaces and in spindle cells, with strong nuclear expression of HHV8.
Reference Gallery:
Nodular-stage Kaposi sarcoma. This example shows a cellular proliferation comprising fascicles of spindle cells, with prominent surrounding haemorrhage. Numerous small slit-like spaces containing erythrocytes are discernible, even at low power, with small numbers of ectatic vessels.
Nodular-stage Kaposi sarcoma. At higher power, the cells are uniform and contain minimally atypical elongated spindled vesicular nuclei.
Kaposi sarcoma. Hyaline globules, which can be intracellular or extracellular, are scattered within this lesion.
Kaposi sarcoma. This example of nodular Kaposi sarcoma shows strong nuclear expression of HHV8 in spindle cells.

Q: Larger, deep-seated lesions of Tufted Angioma and Kaposiform Haemangioendothelioma often present with profound, life-threatening thrombocytopenia due to intralesional platelet trapping, a clinical condition known as the [...].
Kaposiform haemangioendothelioma, classic pattern. Classic histological manifestations of kaposiform haemangioendothelioma, such as prominent endothelial spindling and numerous platelet-rich microthrombi, are best developed in larger, more deeply seated lesions, as shown in this example from the lateral neck of an 8-day-old girl. Platelet-trapping within compressed spaces is highlighted by CD61 immunostaining (not shown) and is the presumed histological correlate of Kasabach–Merritt phenomenon. Note the presence of abnormal lymphatic vasculature in adjacent stroma, a common finding.
Tufted angioma / kaposiform haemangioendothelioma. Kaposiform haemangioendothelioma lesions with both superficial and deep components show transition from smaller superficial tumour nodules with subtle endothelial spindling (tufted angioma pattern) to deeper coalescent nodules with more prominent spindling and platelet-trapping (classic kaposiform haemangioendothelioma pattern).
A: Kasabach-Merritt phenomenon
Back Extra: Tufted Angioma and Kaposiform Haemangioendothelioma
- Clinical: Cutaneous forms of tufted angioma and kaposiform haemangioendothelioma are violaceous, infiltrative patches or plaques that may develop nodularity. Larger, deeper lesions are associated with high mortality due to thrombocytopenia (Kasabach–Merritt phenomenon).
- Micro: Classic kaposiform haemangioendothelioma is characterized by spindled endothelial cells forming elongated slit-like lumina, with prominent platelet trapping and lymphatic vasculature.
- Ancillary: Somatic activating GNA14 mutations have been reported in tufted angioma and kaposiform haemangioendothelioma. Platelet transfusions can exacerbate the Kasabach–Merritt phenomenon by stimulating vascular proliferation.
Reference Gallery:
Tufted angioma / kaposiform haemangioendothelioma. A lesion from the knee in a 5-month-old girl. This kaposiform haemangioendothelioma shows solid growth composed of nests of ovoid cells, forming slit-like lumina. Perineurial invasion is present.
Tufted angioma / kaposiform haemangioendothelioma. This lesion from the buttock of a 5-year-old girl shows tightly packed lobules of capillaries involving subcutis.
Tufted angioma / kaposiform haemangioendothelioma. This lesion shows the typical superficial (tufted angioma) pattern. Higher magnification reveals pinpoint lumina and relatively subtle endothelial cell spindling without nuclear pleomorphism. Mitotic activity is very low.
Tufted angioma / kaposiform haemangioendothelioma. This lesion with a superficial (tufted angioma) pattern shows focal strong positivity for podoplanin within tumour nodules, sharply sparing other areas within the same nodule. A matching pattern of positivity is seen for other lymphatic endothelial markers, including PROX1 and LYVE1, as well as for CD34 (which is normally expressed preferentially in blood vascular endothelial cells).
Kaposiform haemangioendothelioma, classic pattern. Classic histological manifestations of kaposiform haemangioendothelioma, such as prominent endothelial spindling and numerous platelet-rich microthrombi, are best developed in larger, more deeply seated lesions, as shown in this example from the lateral neck of an 8-day-old girl. Platelet-trapping within compressed spaces is highlighted by CD61 immunostaining (not shown) and is the presumed histological correlate of Kasabach–Merritt phenomenon. Note the presence of abnormal lymphatic vasculature in adjacent stroma, a common finding.
Tufted angioma / kaposiform haemangioendothelioma. Within tumour nodules of kaposiform haemangioendothelioma, an alternating pattern of strong positivity and negativity for podoplanin is striking. Note the presence of abnormal lymphatic vasculature in adjacent stroma, a common finding.
Tufted angioma / kaposiform haemangioendothelioma. Kaposiform haemangioendothelioma lesions with both superficial and deep components show transition from smaller superficial tumour nodules with subtle endothelial spindling (tufted angioma pattern) to deeper coalescent nodules with more prominent spindling and platelet-trapping (classic kaposiform haemangioendothelioma pattern).

Q: Microscopic evaluation of Tufted Angioma and Kaposiform Haemangioendothelioma characteristically reveals spindled endothelial cells forming elongated, slit-like lumina containing [...].
Kaposiform haemangioendothelioma, classic pattern. Classic histological manifestations of kaposiform haemangioendothelioma, such as prominent endothelial spindling and numerous platelet-rich microthrombi, are best developed in larger, more deeply seated lesions, as shown in this example from the lateral neck of an 8-day-old girl. Platelet-trapping within compressed spaces is highlighted by CD61 immunostaining (not shown) and is the presumed histological correlate of Kasabach–Merritt phenomenon. Note the presence of abnormal lymphatic vasculature in adjacent stroma, a common finding.
A: platelet-rich microthrombi
Back Extra: Tufted Angioma and Kaposiform Haemangioendothelioma
- Clinical: Cutaneous forms of tufted angioma and kaposiform haemangioendothelioma are violaceous, infiltrative patches or plaques that may develop nodularity. Larger, deeper lesions are associated with high mortality due to thrombocytopenia (Kasabach–Merritt phenomenon).
- Micro: Classic kaposiform haemangioendothelioma is characterized by spindled endothelial cells forming elongated slit-like lumina, with prominent platelet trapping and lymphatic vasculature.
- Ancillary: Somatic activating GNA14 mutations have been reported in tufted angioma and kaposiform haemangioendothelioma. Platelet transfusions can exacerbate the Kasabach–Merritt phenomenon by stimulating vascular proliferation.
Reference Gallery:
Tufted angioma / kaposiform haemangioendothelioma. A lesion from the knee in a 5-month-old girl. This kaposiform haemangioendothelioma shows solid growth composed of nests of ovoid cells, forming slit-like lumina. Perineurial invasion is present.
Tufted angioma / kaposiform haemangioendothelioma. This lesion from the buttock of a 5-year-old girl shows tightly packed lobules of capillaries involving subcutis.
Tufted angioma / kaposiform haemangioendothelioma. This lesion shows the typical superficial (tufted angioma) pattern. Higher magnification reveals pinpoint lumina and relatively subtle endothelial cell spindling without nuclear pleomorphism. Mitotic activity is very low.
Tufted angioma / kaposiform haemangioendothelioma. This lesion with a superficial (tufted angioma) pattern shows focal strong positivity for podoplanin within tumour nodules, sharply sparing other areas within the same nodule. A matching pattern of positivity is seen for other lymphatic endothelial markers, including PROX1 and LYVE1, as well as for CD34 (which is normally expressed preferentially in blood vascular endothelial cells).
Kaposiform haemangioendothelioma, classic pattern. Classic histological manifestations of kaposiform haemangioendothelioma, such as prominent endothelial spindling and numerous platelet-rich microthrombi, are best developed in larger, more deeply seated lesions, as shown in this example from the lateral neck of an 8-day-old girl. Platelet-trapping within compressed spaces is highlighted by CD61 immunostaining (not shown) and is the presumed histological correlate of Kasabach–Merritt phenomenon. Note the presence of abnormal lymphatic vasculature in adjacent stroma, a common finding.
Tufted angioma / kaposiform haemangioendothelioma. Within tumour nodules of kaposiform haemangioendothelioma, an alternating pattern of strong positivity and negativity for podoplanin is striking. Note the presence of abnormal lymphatic vasculature in adjacent stroma, a common finding.
Tufted angioma / kaposiform haemangioendothelioma. Kaposiform haemangioendothelioma lesions with both superficial and deep components show transition from smaller superficial tumour nodules with subtle endothelial spindling (tufted angioma pattern) to deeper coalescent nodules with more prominent spindling and platelet-trapping (classic kaposiform haemangioendothelioma pattern).

Q: A striking immunohistochemical feature of Tufted Angioma and Kaposiform Haemangioendothelioma is the alternating pattern of strong focal expression and distinct absence of the lymphatic marker [...] within the individual tumor nodules.
Tufted angioma / kaposiform haemangioendothelioma. This lesion with a superficial (tufted angioma) pattern shows focal strong positivity for podoplanin within tumour nodules, sharply sparing other areas within the same nodule. A matching pattern of positivity is seen for other lymphatic endothelial markers, including PROX1 and LYVE1, as well as for CD34 (which is normally expressed preferentially in blood vascular endothelial cells).
Tufted angioma / kaposiform haemangioendothelioma. Within tumour nodules of kaposiform haemangioendothelioma, an alternating pattern of strong positivity and negativity for podoplanin is striking. Note the presence of abnormal lymphatic vasculature in adjacent stroma, a common finding.
A: podoplanin
Back Extra: Tufted Angioma and Kaposiform Haemangioendothelioma
- Clinical: Cutaneous forms of tufted angioma and kaposiform haemangioendothelioma are violaceous, infiltrative patches or plaques that may develop nodularity. Larger, deeper lesions are associated with high mortality due to thrombocytopenia (Kasabach–Merritt phenomenon).
- Micro: Classic kaposiform haemangioendothelioma is characterized by spindled endothelial cells forming elongated slit-like lumina, with prominent platelet trapping and lymphatic vasculature.
- Ancillary: Somatic activating GNA14 mutations have been reported in tufted angioma and kaposiform haemangioendothelioma. Platelet transfusions can exacerbate the Kasabach–Merritt phenomenon by stimulating vascular proliferation.
Reference Gallery:
Tufted angioma / kaposiform haemangioendothelioma. A lesion from the knee in a 5-month-old girl. This kaposiform haemangioendothelioma shows solid growth composed of nests of ovoid cells, forming slit-like lumina. Perineurial invasion is present.
Tufted angioma / kaposiform haemangioendothelioma. This lesion from the buttock of a 5-year-old girl shows tightly packed lobules of capillaries involving subcutis.
Tufted angioma / kaposiform haemangioendothelioma. This lesion shows the typical superficial (tufted angioma) pattern. Higher magnification reveals pinpoint lumina and relatively subtle endothelial cell spindling without nuclear pleomorphism. Mitotic activity is very low.
Tufted angioma / kaposiform haemangioendothelioma. This lesion with a superficial (tufted angioma) pattern shows focal strong positivity for podoplanin within tumour nodules, sharply sparing other areas within the same nodule. A matching pattern of positivity is seen for other lymphatic endothelial markers, including PROX1 and LYVE1, as well as for CD34 (which is normally expressed preferentially in blood vascular endothelial cells).
Kaposiform haemangioendothelioma, classic pattern. Classic histological manifestations of kaposiform haemangioendothelioma, such as prominent endothelial spindling and numerous platelet-rich microthrombi, are best developed in larger, more deeply seated lesions, as shown in this example from the lateral neck of an 8-day-old girl. Platelet-trapping within compressed spaces is highlighted by CD61 immunostaining (not shown) and is the presumed histological correlate of Kasabach–Merritt phenomenon. Note the presence of abnormal lymphatic vasculature in adjacent stroma, a common finding.
Tufted angioma / kaposiform haemangioendothelioma. Within tumour nodules of kaposiform haemangioendothelioma, an alternating pattern of strong positivity and negativity for podoplanin is striking. Note the presence of abnormal lymphatic vasculature in adjacent stroma, a common finding.
Tufted angioma / kaposiform haemangioendothelioma. Kaposiform haemangioendothelioma lesions with both superficial and deep components show transition from smaller superficial tumour nodules with subtle endothelial spindling (tufted angioma pattern) to deeper coalescent nodules with more prominent spindling and platelet-trapping (classic kaposiform haemangioendothelioma pattern).

Q: In Papillary intralymphatic angioendothelioma, the lymphatic channels are classically lined by columnar endothelial cells that exhibit a characteristic [...] appearance.
Papillary intralymphatic angioendothelioma. This image shows the intraluminal proliferation of hobnail or matchstick-like columnar endothelial cells.
A: hobnail or matchstick-like
Back Extra: Papillary intralymphatic angioendothelioma
- Clinical: Papillary intralymphatic angioendothelioma (PILA) most often involves the proximal extremities, presenting as a slow-growing asymptomatic cutaneous induration, plaque, or rarely nodule.
- Micro: The microscopic appearance of PILA includes an extensive proliferation of lymphatic channels lined by columnar, matchstick-like, or hobnail endothelial cells, with intraluminal papillary tufts and proteinaceous fluid.
- Ancillary: Tumour cells express pan-endothelial markers (CD31, ERG) and lymphatic endothelial markers (podoplanin, VEGFR3, PROX1).
Reference Gallery:
Papillary intralymphatic angioendothelioma. This is a rare intraosseous papillary intralymphatic angioendothelioma of the clavicle that is a lytic destructive lesion, seen here on radiological CT without contrast (left) and with contrast (right).
Papillary intralymphatic angioendothelioma. This is a gross photograph of the lesion shown in Fig. #6108. Notice the extensive vascular proliferation of clavicle and the extension into soft tissue around the bone.
Papillary intralymphatic angioendothelioma. There is a background of lymphangiomatosis with intraluminal proteinaceous fluid and stromal lymphocytes.
Papillary intralymphatic angioendothelioma. There is a background of lymphangiomatosis with intraluminal proteinaceous fluid and stromal lymphocytes.
Papillary intralymphatic angioendothelioma. This image shows the intraluminal proliferation of hobnail or matchstick-like columnar endothelial cells.
Papillary intralymphatic angioendothelioma. The hobnail or matchstick-like columnar endothelial cells shown in Fig. #7573 and Fig. #7574 are immunopositive for VEGFR3.

Q: The tumor cells in Papillary intralymphatic angioendothelioma express pan-endothelial markers as well as lymphatic endothelial markers like podoplanin, PROX1, and [...].
Papillary intralymphatic angioendothelioma. The hobnail or matchstick-like columnar endothelial cells shown in Fig. #7573 and Fig. #7574 are immunopositive for VEGFR3.
A: VEGFR3
Back Extra: Papillary intralymphatic angioendothelioma
- Clinical: Papillary intralymphatic angioendothelioma (PILA) most often involves the proximal extremities, presenting as a slow-growing asymptomatic cutaneous induration, plaque, or rarely nodule.
- Micro: The microscopic appearance of PILA includes an extensive proliferation of lymphatic channels lined by columnar, matchstick-like, or hobnail endothelial cells, with intraluminal papillary tufts and proteinaceous fluid.
- Ancillary: Tumour cells express pan-endothelial markers (CD31, ERG) and lymphatic endothelial markers (podoplanin, VEGFR3, PROX1).
Reference Gallery:
Papillary intralymphatic angioendothelioma. This is a rare intraosseous papillary intralymphatic angioendothelioma of the clavicle that is a lytic destructive lesion, seen here on radiological CT without contrast (left) and with contrast (right).
Papillary intralymphatic angioendothelioma. This is a gross photograph of the lesion shown in Fig. #6108. Notice the extensive vascular proliferation of clavicle and the extension into soft tissue around the bone.
Papillary intralymphatic angioendothelioma. There is a background of lymphangiomatosis with intraluminal proteinaceous fluid and stromal lymphocytes.
Papillary intralymphatic angioendothelioma. There is a background of lymphangiomatosis with intraluminal proteinaceous fluid and stromal lymphocytes.
Papillary intralymphatic angioendothelioma. This image shows the intraluminal proliferation of hobnail or matchstick-like columnar endothelial cells.
Papillary intralymphatic angioendothelioma. The hobnail or matchstick-like columnar endothelial cells shown in Fig. #7573 and Fig. #7574 are immunopositive for VEGFR3.

Q: Though usually cutaneous, Papillary intralymphatic angioendothelioma may rarely involve bone, presenting radiographically as a [...] lesion.
Papillary intralymphatic angioendothelioma. This is a rare intraosseous papillary intralymphatic angioendothelioma of the clavicle that is a lytic destructive lesion, seen here on radiological CT without contrast (left) and with contrast (right).
Papillary intralymphatic angioendothelioma. This is a gross photograph of the lesion shown in Fig. #6108. Notice the extensive vascular proliferation of clavicle and the extension into soft tissue around the bone.
A: lytic destructive
Back Extra: Papillary intralymphatic angioendothelioma
- Clinical: Papillary intralymphatic angioendothelioma (PILA) most often involves the proximal extremities, presenting as a slow-growing asymptomatic cutaneous induration, plaque, or rarely nodule.
- Micro: The microscopic appearance of PILA includes an extensive proliferation of lymphatic channels lined by columnar, matchstick-like, or hobnail endothelial cells, with intraluminal papillary tufts and proteinaceous fluid.
- Ancillary: Tumour cells express pan-endothelial markers (CD31, ERG) and lymphatic endothelial markers (podoplanin, VEGFR3, PROX1).
Reference Gallery:
Papillary intralymphatic angioendothelioma. This is a rare intraosseous papillary intralymphatic angioendothelioma of the clavicle that is a lytic destructive lesion, seen here on radiological CT without contrast (left) and with contrast (right).
Papillary intralymphatic angioendothelioma. This is a gross photograph of the lesion shown in Fig. #6108. Notice the extensive vascular proliferation of clavicle and the extension into soft tissue around the bone.
Papillary intralymphatic angioendothelioma. There is a background of lymphangiomatosis with intraluminal proteinaceous fluid and stromal lymphocytes.
Papillary intralymphatic angioendothelioma. There is a background of lymphangiomatosis with intraluminal proteinaceous fluid and stromal lymphocytes.
Papillary intralymphatic angioendothelioma. This image shows the intraluminal proliferation of hobnail or matchstick-like columnar endothelial cells.
Papillary intralymphatic angioendothelioma. The hobnail or matchstick-like columnar endothelial cells shown in Fig. #7573 and Fig. #7574 are immunopositive for VEGFR3.

Q: Histologically, Pseudomyogenic haemangioendothelioma is composed of sheets and loose fascicles of plump spindle cells with abundant, brightly eosinophilic cytoplasm that can mimic [...].
Pseudomyogenic haemangioendothelioma. Some tumour cells with brightly eosinophilic cytoplasm resemble rhabdomyoblasts.
A: rhabdomyoblasts
Back Extra: Pseudomyogenic haemangioendothelioma
- Clinical: About 50% of patients with pseudomyogenic haemangioendothelioma present with painless nodules, while the other half present with painful nodules, often multifocal and involving multiple tissue planes.
- Micro: The tumour is composed of sheets and loose fascicles of plump spindle cells with abundant, brightly eosinophilic cytoplasm, sometimes mimicking rhabdomyoblasts. A minor component of epithelioid cells is often present.
- Ancillary: Immunohistochemistry shows diffuse expression of keratins (AE1/AE3) and the endothelial transcription factors FLI1 and ERG. Strong nuclear staining for FOSB is a consistent finding.
Reference Gallery:
Pseudomyogenic haemangioendothelioma. Bone scan from a patient with pseudomyogenic haemangioendothelioma showing multiple lesions involving the tibia and ankle.
Pseudomyogenic haemangioendothelioma. Scanning image from a multifocal intramuscular pseudomyogenic haemangioendothelioma of the lower leg.
Pseudomyogenic haemangioendothelioma. Immunohistochemistry for FOSB is strongly positive in tumour cells and highlights the multifocality.
Pseudomyogenic haemangioendothelioma. FDG PET from a patient with pseudomyogenic haemangioendothelioma showing multiple lesions in the foot.
Pseudomyogenic haemangioendothelioma. Some tumour cells with brightly eosinophilic cytoplasm resemble rhabdomyoblasts.
Pseudomyogenic haemangioendothelioma. Prominent stromal neutrophils can be seen in this example. Note the scattered tumour cells with a more epithelioid appearance.
Pseudomyogenic haemangioendothelioma. The tumour shows infiltrative margins into adjacent skeletal muscle.
Pseudomyogenic haemangioendothelioma. Diffuse expression of keratin AE1/AE3.
Pseudomyogenic haemangioendothelioma. Strong nuclear staining for the endothelial transcription factor ERG.

Q: In addition to diffuse keratin (AE1/AE3) and endothelial markers (FLI1, ERG), a highly specific and consistent immunohistochemical finding in Pseudomyogenic haemangioendothelioma is strong nuclear staining for [...].
Pseudomyogenic haemangioendothelioma. Immunohistochemistry for FOSB is strongly positive in tumour cells and highlights the multifocality.
Pseudomyogenic haemangioendothelioma. Diffuse expression of keratin AE1/AE3.
Pseudomyogenic haemangioendothelioma. Strong nuclear staining for the endothelial transcription factor ERG.
A: FOSB
Back Extra: Pseudomyogenic haemangioendothelioma
- Clinical: About 50% of patients with pseudomyogenic haemangioendothelioma present with painless nodules, while the other half present with painful nodules, often multifocal and involving multiple tissue planes.
- Micro: The tumour is composed of sheets and loose fascicles of plump spindle cells with abundant, brightly eosinophilic cytoplasm, sometimes mimicking rhabdomyoblasts. A minor component of epithelioid cells is often present.
- Ancillary: Immunohistochemistry shows diffuse expression of keratins (AE1/AE3) and the endothelial transcription factors FLI1 and ERG. Strong nuclear staining for FOSB is a consistent finding.
Reference Gallery:
Pseudomyogenic haemangioendothelioma. Bone scan from a patient with pseudomyogenic haemangioendothelioma showing multiple lesions involving the tibia and ankle.
Pseudomyogenic haemangioendothelioma. Scanning image from a multifocal intramuscular pseudomyogenic haemangioendothelioma of the lower leg.
Pseudomyogenic haemangioendothelioma. Immunohistochemistry for FOSB is strongly positive in tumour cells and highlights the multifocality.
Pseudomyogenic haemangioendothelioma. FDG PET from a patient with pseudomyogenic haemangioendothelioma showing multiple lesions in the foot.
Pseudomyogenic haemangioendothelioma. Some tumour cells with brightly eosinophilic cytoplasm resemble rhabdomyoblasts.
Pseudomyogenic haemangioendothelioma. Prominent stromal neutrophils can be seen in this example. Note the scattered tumour cells with a more epithelioid appearance.
Pseudomyogenic haemangioendothelioma. The tumour shows infiltrative margins into adjacent skeletal muscle.
Pseudomyogenic haemangioendothelioma. Diffuse expression of keratin AE1/AE3.
Pseudomyogenic haemangioendothelioma. Strong nuclear staining for the endothelial transcription factor ERG.

Q: Clinically and radiographically (e.g., on bone scan or FDG PET), Pseudomyogenic haemangioendothelioma frequently presents as [...] nodules that often involve multiple tissue planes.
Pseudomyogenic haemangioendothelioma. Bone scan from a patient with pseudomyogenic haemangioendothelioma showing multiple lesions involving the tibia and ankle.
Pseudomyogenic haemangioendothelioma. FDG PET from a patient with pseudomyogenic haemangioendothelioma showing multiple lesions in the foot.
A: multifocal
Back Extra: Pseudomyogenic haemangioendothelioma
- Clinical: About 50% of patients with pseudomyogenic haemangioendothelioma present with painless nodules, while the other half present with painful nodules, often multifocal and involving multiple tissue planes.
- Micro: The tumour is composed of sheets and loose fascicles of plump spindle cells with abundant, brightly eosinophilic cytoplasm, sometimes mimicking rhabdomyoblasts. A minor component of epithelioid cells is often present.
- Ancillary: Immunohistochemistry shows diffuse expression of keratins (AE1/AE3) and the endothelial transcription factors FLI1 and ERG. Strong nuclear staining for FOSB is a consistent finding.
Reference Gallery:
Pseudomyogenic haemangioendothelioma. Bone scan from a patient with pseudomyogenic haemangioendothelioma showing multiple lesions involving the tibia and ankle.
Pseudomyogenic haemangioendothelioma. Scanning image from a multifocal intramuscular pseudomyogenic haemangioendothelioma of the lower leg.
Pseudomyogenic haemangioendothelioma. Immunohistochemistry for FOSB is strongly positive in tumour cells and highlights the multifocality.
Pseudomyogenic haemangioendothelioma. FDG PET from a patient with pseudomyogenic haemangioendothelioma showing multiple lesions in the foot.
Pseudomyogenic haemangioendothelioma. Some tumour cells with brightly eosinophilic cytoplasm resemble rhabdomyoblasts.
Pseudomyogenic haemangioendothelioma. Prominent stromal neutrophils can be seen in this example. Note the scattered tumour cells with a more epithelioid appearance.
Pseudomyogenic haemangioendothelioma. The tumour shows infiltrative margins into adjacent skeletal muscle.
Pseudomyogenic haemangioendothelioma. Diffuse expression of keratin AE1/AE3.
Pseudomyogenic haemangioendothelioma. Strong nuclear staining for the endothelial transcription factor ERG.

Q: Microscopically, Retiform Haemangioendothelioma features an infiltrative growth of elongated, narrow, arborizing vascular channels that distinctly resemble the [...].
Retiform haemangioendothelioma. A cutaneous example showing an infiltrative growth of well-formed elongated vessels reminiscent of rete testis pattern.
Retiform haemangioendothelioma. Branching vessels within a sclerotic stroma with associated lymphocytic infiltrate. Dabska-like intravascular papillary structures are present.
A: rete testis
Back Extra: Retiform Haemangioendothelioma
- Clinical: Retiform haemangioendothelioma presents as a red/bluish slow-growing plaque or nodule, usually < 3 cm in size, and is most commonly found in the distal extremities.
- Micro: Characterized by elongated and narrow arborizing vascular channels with hobnail endothelial cells and a prominent stromal lymphocytic infiltrate.
- Ancillary: The neoplastic cells stain positive for vascular markers (CD31, CD34, ERG) and lymphatic marker PROX1, but are negative for HHV8.
Reference Gallery:
Retiform haemangioendothelioma. A cutaneous example showing an infiltrative growth of well-formed elongated vessels reminiscent of rete testis pattern.
Retiform haemangioendothelioma. Branching vessels within a sclerotic stroma with associated lymphocytic infiltrate. Dabska-like intravascular papillary structures are present.
Retiform haemangioendothelioma. High-power view showing vascular structures lined by monomorphic hobnail endothelial cells, lacking nuclear pleomorphism or increased mitotic activity.
Retiform haemangioendothelioma. Diffuse podoplanin expression, confirming lymphatic endothelial phenotype.

Q: At high magnification, the branching vessels in Retiform Haemangioendothelioma are characteristically lined by monomorphic [...] endothelial cells that protrude into the lumens without significant pleomorphism.
Retiform haemangioendothelioma. High-power view showing vascular structures lined by monomorphic hobnail endothelial cells, lacking nuclear pleomorphism or increased mitotic activity.
A: hobnail
Back Extra: Retiform Haemangioendothelioma
- Clinical: Retiform haemangioendothelioma presents as a red/bluish slow-growing plaque or nodule, usually < 3 cm in size, and is most commonly found in the distal extremities.
- Micro: Characterized by elongated and narrow arborizing vascular channels with hobnail endothelial cells and a prominent stromal lymphocytic infiltrate.
- Ancillary: The neoplastic cells stain positive for vascular markers (CD31, CD34, ERG) and lymphatic marker PROX1, but are negative for HHV8.
Reference Gallery:
Retiform haemangioendothelioma. A cutaneous example showing an infiltrative growth of well-formed elongated vessels reminiscent of rete testis pattern.
Retiform haemangioendothelioma. Branching vessels within a sclerotic stroma with associated lymphocytic infiltrate. Dabska-like intravascular papillary structures are present.
Retiform haemangioendothelioma. High-power view showing vascular structures lined by monomorphic hobnail endothelial cells, lacking nuclear pleomorphism or increased mitotic activity.
Retiform haemangioendothelioma. Diffuse podoplanin expression, confirming lymphatic endothelial phenotype.

Q: In addition to general vascular markers (CD31, CD34, ERG), the tumor cells in Retiform Haemangioendothelioma characteristically express markers of lymphatic differentiation, such as PROX1 and diffuse [...].
Retiform haemangioendothelioma. Diffuse podoplanin expression, confirming lymphatic endothelial phenotype.
A: podoplanin
Back Extra: Retiform Haemangioendothelioma
- Clinical: Retiform haemangioendothelioma presents as a red/bluish slow-growing plaque or nodule, usually < 3 cm in size, and is most commonly found in the distal extremities.
- Micro: Characterized by elongated and narrow arborizing vascular channels with hobnail endothelial cells and a prominent stromal lymphocytic infiltrate.
- Ancillary: The neoplastic cells stain positive for vascular markers (CD31, CD34, ERG) and lymphatic marker PROX1, but are negative for HHV8.
Reference Gallery:
Retiform haemangioendothelioma. A cutaneous example showing an infiltrative growth of well-formed elongated vessels reminiscent of rete testis pattern.
Retiform haemangioendothelioma. Branching vessels within a sclerotic stroma with associated lymphocytic infiltrate. Dabska-like intravascular papillary structures are present.
Retiform haemangioendothelioma. High-power view showing vascular structures lined by monomorphic hobnail endothelial cells, lacking nuclear pleomorphism or increased mitotic activity.
Retiform haemangioendothelioma. Diffuse podoplanin expression, confirming lymphatic endothelial phenotype.

Q: Clinically, cutaneous Angiosarcoma typically presents as rapidly growing, poorly defined, purple to bluish-black coalescing macules and papules that often exhibit extensive [...] and coagulopathy.
Angiosarcoma. This tumour, present on the lower extremity, is composed of markedly haemorrhagic, purple to bluish-black coalescing macules and papules.
Angiosarcoma with thrombus. This tumour is present amid extensive organizing haemorrhage and thrombus. Sometimes this can be so extensive that it obscures much of the neoplasm.
A: hemorrhage
Back Extra: Angiosarcoma
- Clinical: Angiosarcomas often present as poorly defined, rapidly growing, and sometimes painful masses, with a high incidence of haemorrhage and coagulopathy.
- Micro: Angiosarcomas can show a mixture of well-formed vascular channels and solid sheets of epithelioid or spindled cells, with high-grade morphology and significant cytological atypia.
- Ancillary: MYC amplification is frequently observed in postirradiation and chronic lymphoedema-associated angiosarcomas, and can help in the diagnosis.
Reference Gallery:
Well-differentiated angiosarcoma. This lesion shows well-formed (although angulated and irregular) vascular spaces lined by mildly atypical flattened endothelial cells.
Angiosarcoma. This tumour, present on the lower extremity, is composed of markedly haemorrhagic, purple to bluish-black coalescing macules and papules.
Angiosarcoma with thrombus. This tumour is present amid extensive organizing haemorrhage and thrombus. Sometimes this can be so extensive that it obscures much of the neoplasm.
Cutaneous angiosarcoma. The dermis contains ill-defined tumour composed of irregular vascular channels lined by hyperchromatic, moderately atypical vascular endothelial cells. There is a marked surrounding chronic inflammatory infiltrate that makes the tumour difficult to discern.
Epithelioid angiosarcoma. The tumour is composed of predominantly solid distributions of moderately atypical, large epithelioid cells with ovoid vesicular nuclei and prominent nuclei.
Angiosarcoma. A poorly differentiated angiosarcoma composed of sheets of epithelioid and spindle cells with amphophilic cytoplasm.
Angiosarcoma. Nuclear immunoreactivity for ERG, the most sensitive and specific endothelial marker. In the absence of a vasoformative component, confirmation of endothelial differentiation by immunohistochemistry is critical.

Q: A characteristic histologic feature of well-differentiated Angiosarcoma is the presence of irregular, [...] vascular channels lined by mildly to moderately atypical, hyperchromatic endothelial cells.
Well-differentiated angiosarcoma. This lesion shows well-formed (although angulated and irregular) vascular spaces lined by mildly atypical flattened endothelial cells.
Cutaneous angiosarcoma. The dermis contains ill-defined tumour composed of irregular vascular channels lined by hyperchromatic, moderately atypical vascular endothelial cells. There is a marked surrounding chronic inflammatory infiltrate that makes the tumour difficult to discern.
A: angulated
Back Extra: Angiosarcoma
- Clinical: Angiosarcomas often present as poorly defined, rapidly growing, and sometimes painful masses, with a high incidence of haemorrhage and coagulopathy.
- Micro: Angiosarcomas can show a mixture of well-formed vascular channels and solid sheets of epithelioid or spindled cells, with high-grade morphology and significant cytological atypia.
- Ancillary: MYC amplification is frequently observed in postirradiation and chronic lymphoedema-associated angiosarcomas, and can help in the diagnosis.
Reference Gallery:
Well-differentiated angiosarcoma. This lesion shows well-formed (although angulated and irregular) vascular spaces lined by mildly atypical flattened endothelial cells.
Angiosarcoma. This tumour, present on the lower extremity, is composed of markedly haemorrhagic, purple to bluish-black coalescing macules and papules.
Angiosarcoma with thrombus. This tumour is present amid extensive organizing haemorrhage and thrombus. Sometimes this can be so extensive that it obscures much of the neoplasm.
Cutaneous angiosarcoma. The dermis contains ill-defined tumour composed of irregular vascular channels lined by hyperchromatic, moderately atypical vascular endothelial cells. There is a marked surrounding chronic inflammatory infiltrate that makes the tumour difficult to discern.
Epithelioid angiosarcoma. The tumour is composed of predominantly solid distributions of moderately atypical, large epithelioid cells with ovoid vesicular nuclei and prominent nuclei.
Angiosarcoma. A poorly differentiated angiosarcoma composed of sheets of epithelioid and spindle cells with amphophilic cytoplasm.
Angiosarcoma. Nuclear immunoreactivity for ERG, the most sensitive and specific endothelial marker. In the absence of a vasoformative component, confirmation of endothelial differentiation by immunohistochemistry is critical.

Q: Because solid and poorly differentiated variants of Angiosarcoma can lack obvious vasoformative features, diagnosis often relies on demonstrating strong nuclear immunoreactivity for the sensitive and specific endothelial marker [...].
Angiosarcoma. A poorly differentiated angiosarcoma composed of sheets of epithelioid and spindle cells with amphophilic cytoplasm.
Angiosarcoma. Nuclear immunoreactivity for ERG, the most sensitive and specific endothelial marker. In the absence of a vasoformative component, confirmation of endothelial differentiation by immunohistochemistry is critical.
A: ERG
Back Extra: Angiosarcoma
- Clinical: Angiosarcomas often present as poorly defined, rapidly growing, and sometimes painful masses, with a high incidence of haemorrhage and coagulopathy.
- Micro: Angiosarcomas can show a mixture of well-formed vascular channels and solid sheets of epithelioid or spindled cells, with high-grade morphology and significant cytological atypia.
- Ancillary: MYC amplification is frequently observed in postirradiation and chronic lymphoedema-associated angiosarcomas, and can help in the diagnosis.
Reference Gallery:
Well-differentiated angiosarcoma. This lesion shows well-formed (although angulated and irregular) vascular spaces lined by mildly atypical flattened endothelial cells.
Angiosarcoma. This tumour, present on the lower extremity, is composed of markedly haemorrhagic, purple to bluish-black coalescing macules and papules.
Angiosarcoma with thrombus. This tumour is present amid extensive organizing haemorrhage and thrombus. Sometimes this can be so extensive that it obscures much of the neoplasm.
Cutaneous angiosarcoma. The dermis contains ill-defined tumour composed of irregular vascular channels lined by hyperchromatic, moderately atypical vascular endothelial cells. There is a marked surrounding chronic inflammatory infiltrate that makes the tumour difficult to discern.
Epithelioid angiosarcoma. The tumour is composed of predominantly solid distributions of moderately atypical, large epithelioid cells with ovoid vesicular nuclei and prominent nuclei.
Angiosarcoma. A poorly differentiated angiosarcoma composed of sheets of epithelioid and spindle cells with amphophilic cytoplasm.
Angiosarcoma. Nuclear immunoreactivity for ERG, the most sensitive and specific endothelial marker. In the absence of a vasoformative component, confirmation of endothelial differentiation by immunohistochemistry is critical.

Q: Histologically, Epithelioid Haemangioendothelioma typically presents as cords and nests of epithelioid cells embedded in a distinctive [...] (or sclerotic) stroma.
Epithelioid haemangioendothelioma. The lesional cells in this example range from nests of epithelioid cells to more spindled cells focally. Note the fibromyxoid matrix.
Epithelioid haemangioendothelioma. Typical appearance, with nests and cords of epithelioid cells set in a sclerotic matrix.
A: myxohyaline
Back Extra: Epithelioid Haemangioendothelioma
- Clinical: Epithelioid haemangioendothelioma usually presents as a painful mass in soft tissues, and can cause symptoms of vascular occlusion such as oedema and thrombophlebitis.
- Micro: Characterized by cords and nests of epithelioid cells in a myxohyaline stroma, with minimal atypia and low mitotic count. Tumors with YAP1-TFE3 fusion show more eosinophilic cytoplasm and solid growth.
- Ancillary: Immunohistochemistry shows strong nuclear expression of CAMTA1 in WWTR1-CAMTA1 fusion cases, and TFE3 in YAP1-TFE3 fusion cases, aiding in diagnosis.
Reference Gallery:
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma infiltrating adipose tissue.
Epithelioid haemangioendothelioma. The lesional cells in this example range from nests of epithelioid cells to more spindled cells focally. Note the fibromyxoid matrix.
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma with a more spindled appearance than is typical.
Epithelioid haemangioendothelioma. Typical appearance, with nests and cords of epithelioid cells set in a sclerotic matrix.
Epithelioid haemangioendothelioma. Diffuse and strong immunoreactivity for ERG.
Epithelioid haemangioendothelioma. Diffuse and strong immunoreactivity for CAMTA1.
Epithelioid haemangioendothelioma with YAP1-TFE3 gene fusion. YAP1-TFE3–rearranged epithelioid haemangioendothelioma composed of nests of epithelioid cells infiltrating fibrous tissue. Note the focal cytoplasmic vacuolization.
Epithelioid haemangioendothelioma with YAP1-TFE3 gene fusion. Diffuse and strong immunoreactivity for TFE3.
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma with spindle/sarcomatous features and increased nuclear pleomorphism.
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma with malignant histological features and increased nuclear pleomorphism.

Q: The diagnosis of Epithelioid Haemangioendothelioma is heavily supported by the presence of a WWTR1-CAMTA1 gene fusion, which results in strong nuclear immunohistochemical expression of [...].
Epithelioid haemangioendothelioma. Diffuse and strong immunoreactivity for CAMTA1.
A: CAMTA1
Back Extra: Epithelioid Haemangioendothelioma
- Clinical: Epithelioid haemangioendothelioma usually presents as a painful mass in soft tissues, and can cause symptoms of vascular occlusion such as oedema and thrombophlebitis.
- Micro: Characterized by cords and nests of epithelioid cells in a myxohyaline stroma, with minimal atypia and low mitotic count. Tumors with YAP1-TFE3 fusion show more eosinophilic cytoplasm and solid growth.
- Ancillary: Immunohistochemistry shows strong nuclear expression of CAMTA1 in WWTR1-CAMTA1 fusion cases, and TFE3 in YAP1-TFE3 fusion cases, aiding in diagnosis.
Reference Gallery:
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma infiltrating adipose tissue.
Epithelioid haemangioendothelioma. The lesional cells in this example range from nests of epithelioid cells to more spindled cells focally. Note the fibromyxoid matrix.
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma with a more spindled appearance than is typical.
Epithelioid haemangioendothelioma. Typical appearance, with nests and cords of epithelioid cells set in a sclerotic matrix.
Epithelioid haemangioendothelioma. Diffuse and strong immunoreactivity for ERG.
Epithelioid haemangioendothelioma. Diffuse and strong immunoreactivity for CAMTA1.
Epithelioid haemangioendothelioma with YAP1-TFE3 gene fusion. YAP1-TFE3–rearranged epithelioid haemangioendothelioma composed of nests of epithelioid cells infiltrating fibrous tissue. Note the focal cytoplasmic vacuolization.
Epithelioid haemangioendothelioma with YAP1-TFE3 gene fusion. Diffuse and strong immunoreactivity for TFE3.
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma with spindle/sarcomatous features and increased nuclear pleomorphism.
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma with malignant histological features and increased nuclear pleomorphism.

Q: A distinct subset of Epithelioid Haemangioendothelioma features more solid tumor growth with eosinophilic cytoplasm driven by a YAP1-TFE3 gene fusion, which can be confirmed by strong nuclear immunoreactivity for [...].
Epithelioid haemangioendothelioma with YAP1-TFE3 gene fusion. YAP1-TFE3–rearranged epithelioid haemangioendothelioma composed of nests of epithelioid cells infiltrating fibrous tissue. Note the focal cytoplasmic vacuolization.
Epithelioid haemangioendothelioma with YAP1-TFE3 gene fusion. Diffuse and strong immunoreactivity for TFE3.
A: TFE3
Back Extra: Epithelioid Haemangioendothelioma
- Clinical: Epithelioid haemangioendothelioma usually presents as a painful mass in soft tissues, and can cause symptoms of vascular occlusion such as oedema and thrombophlebitis.
- Micro: Characterized by cords and nests of epithelioid cells in a myxohyaline stroma, with minimal atypia and low mitotic count. Tumors with YAP1-TFE3 fusion show more eosinophilic cytoplasm and solid growth.
- Ancillary: Immunohistochemistry shows strong nuclear expression of CAMTA1 in WWTR1-CAMTA1 fusion cases, and TFE3 in YAP1-TFE3 fusion cases, aiding in diagnosis.
Reference Gallery:
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma infiltrating adipose tissue.
Epithelioid haemangioendothelioma. The lesional cells in this example range from nests of epithelioid cells to more spindled cells focally. Note the fibromyxoid matrix.
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma with a more spindled appearance than is typical.
Epithelioid haemangioendothelioma. Typical appearance, with nests and cords of epithelioid cells set in a sclerotic matrix.
Epithelioid haemangioendothelioma. Diffuse and strong immunoreactivity for ERG.
Epithelioid haemangioendothelioma. Diffuse and strong immunoreactivity for CAMTA1.
Epithelioid haemangioendothelioma with YAP1-TFE3 gene fusion. YAP1-TFE3–rearranged epithelioid haemangioendothelioma composed of nests of epithelioid cells infiltrating fibrous tissue. Note the focal cytoplasmic vacuolization.
Epithelioid haemangioendothelioma with YAP1-TFE3 gene fusion. Diffuse and strong immunoreactivity for TFE3.
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma with spindle/sarcomatous features and increased nuclear pleomorphism.
Epithelioid haemangioendothelioma. Epithelioid haemangioendothelioma with malignant histological features and increased nuclear pleomorphism.

Q: Clinically and grossly, Intimal Sarcoma frequently presents as a solid intraluminal tumor mass causing recurrent embolic disease by obstructing the [...].
Intimal sarcoma. CT of a patient with intimal sarcoma of the right pulmonary artery demonstrating a solid intraluminal mass, which showed metabolic activity on PET-CT (not pictured).
Intimal sarcoma. View of the hilum of the resected lung of a patient with obstruction of the lumen of the pulmonary artery by tumour tissue.
Intimal sarcoma. Endarterectomy specimen of another patient with intimal sarcoma of the pulmonary artery.
A: pulmonary artery
Back Extra: Intimal Sarcoma
- Clinical: Intimal sarcoma often presents with nonspecific symptoms, commonly related to tumour emboli, with recurrent pulmonary embolic disease being the most frequent presentation.
- Micro: The tumour consists of atypical spindle cells with varying degrees of mitotic activity, necrosis, and nuclear polymorphism. Some cases may show myxoid areas or resemble leiomyosarcoma.
- Ancillary: MDM2 amplification is a key molecular alteration, and high-level amplification of PDGFRA and KIT is frequently observed.
Reference Gallery:
Intimal sarcoma. CT of a patient with intimal sarcoma of the right pulmonary artery demonstrating a solid intraluminal mass, which showed metabolic activity on PET-CT (not pictured).
Intimal sarcoma. Spreading of the tumour along the intrapulmonary branches of the pulmonary artery.
Intimal sarcoma. View of the hilum of the resected lung of a patient with obstruction of the lumen of the pulmonary artery by tumour tissue.
Intimal sarcoma. Endarterectomy specimen of another patient with intimal sarcoma of the pulmonary artery.
Intimal sarcoma. Myxoid tumour with low cellular density.
Intimal sarcoma. Bundles of tumour cells resembling leiomyosarcoma.
Intimal sarcoma. An endothelium-lined vascular cleft surrounded by pleomorphic tumour cells.
Intimal sarcoma. Nuclear immunoexpression of MDM2 protein in numerous tumour cells.
Intimal sarcoma. A representative copy-number alteration profile (Agilent 244K array comparative genomic hybridization) showing high-level amplification of the PDGFRA/4q12 and MDM2/12q14-q15 regions; gain of 6q, 7, 8q, 12p, and 17q; and partial/total losses of 1p, 3q, 5q, 9p, 10, 15q, 18, and X. The individual probes are arranged according to their genomic location (x axis) and their respective tumour/reference log2 ratios (y axis). B Array comparative genomic hybridization profile of a selected region of chromosome band 4q12, showing high-level amplification of the genes CHIC2, PDGFRA, and KIT. C A representative example of dual-colour interphase FISH images of intimal sarcoma, showing exclusive high-level amplification of PDGFRA (red signals; long arrows) or MDM2 (green signals; short arrows), intermingled with cells showing separate amplicons for both genes.

Q: The key molecular alteration used to support a diagnosis of Intimal Sarcoma is the amplification of [...], which can be demonstrated by nuclear immunohistochemistry and is often seen alongside PDGFRA amplification.
Intimal sarcoma. Nuclear immunoexpression of MDM2 protein in numerous tumour cells.
Intimal sarcoma. A representative copy-number alteration profile (Agilent 244K array comparative genomic hybridization) showing high-level amplification of the PDGFRA/4q12 and MDM2/12q14-q15 regions; gain of 6q, 7, 8q, 12p, and 17q; and partial/total losses of 1p, 3q, 5q, 9p, 10, 15q, 18, and X. The individual probes are arranged according to their genomic location (x axis) and their respective tumour/reference log2 ratios (y axis). B Array comparative genomic hybridization profile of a selected region of chromosome band 4q12, showing high-level amplification of the genes CHIC2, PDGFRA, and KIT. C A representative example of dual-colour interphase FISH images of intimal sarcoma, showing exclusive high-level amplification of PDGFRA (red signals; long arrows) or MDM2 (green signals; short arrows), intermingled with cells showing separate amplicons for both genes.
A: MDM2
Back Extra: Intimal Sarcoma
- Clinical: Intimal sarcoma often presents with nonspecific symptoms, commonly related to tumour emboli, with recurrent pulmonary embolic disease being the most frequent presentation.
- Micro: The tumour consists of atypical spindle cells with varying degrees of mitotic activity, necrosis, and nuclear polymorphism. Some cases may show myxoid areas or resemble leiomyosarcoma.
- Ancillary: MDM2 amplification is a key molecular alteration, and high-level amplification of PDGFRA and KIT is frequently observed.
Reference Gallery:
Intimal sarcoma. CT of a patient with intimal sarcoma of the right pulmonary artery demonstrating a solid intraluminal mass, which showed metabolic activity on PET-CT (not pictured).
Intimal sarcoma. Spreading of the tumour along the intrapulmonary branches of the pulmonary artery.
Intimal sarcoma. View of the hilum of the resected lung of a patient with obstruction of the lumen of the pulmonary artery by tumour tissue.
Intimal sarcoma. Endarterectomy specimen of another patient with intimal sarcoma of the pulmonary artery.
Intimal sarcoma. Myxoid tumour with low cellular density.
Intimal sarcoma. Bundles of tumour cells resembling leiomyosarcoma.
Intimal sarcoma. An endothelium-lined vascular cleft surrounded by pleomorphic tumour cells.
Intimal sarcoma. Nuclear immunoexpression of MDM2 protein in numerous tumour cells.
Intimal sarcoma. A representative copy-number alteration profile (Agilent 244K array comparative genomic hybridization) showing high-level amplification of the PDGFRA/4q12 and MDM2/12q14-q15 regions; gain of 6q, 7, 8q, 12p, and 17q; and partial/total losses of 1p, 3q, 5q, 9p, 10, 15q, 18, and X. The individual probes are arranged according to their genomic location (x axis) and their respective tumour/reference log2 ratios (y axis). B Array comparative genomic hybridization profile of a selected region of chromosome band 4q12, showing high-level amplification of the genes CHIC2, PDGFRA, and KIT. C A representative example of dual-colour interphase FISH images of intimal sarcoma, showing exclusive high-level amplification of PDGFRA (red signals; long arrows) or MDM2 (green signals; short arrows), intermingled with cells showing separate amplicons for both genes.

Q: Although typically composed of atypical pleomorphic spindle cells, the histology of Intimal Sarcoma can sometimes exhibit low-density myxoid areas or bundle-forming cells that closely resemble [...].
Intimal sarcoma. Myxoid tumour with low cellular density.
Intimal sarcoma. Bundles of tumour cells resembling leiomyosarcoma.
A: leiomyosarcoma
Back Extra: Intimal Sarcoma
- Clinical: Intimal sarcoma often presents with nonspecific symptoms, commonly related to tumour emboli, with recurrent pulmonary embolic disease being the most frequent presentation.
- Micro: The tumour consists of atypical spindle cells with varying degrees of mitotic activity, necrosis, and nuclear polymorphism. Some cases may show myxoid areas or resemble leiomyosarcoma.
- Ancillary: MDM2 amplification is a key molecular alteration, and high-level amplification of PDGFRA and KIT is frequently observed.
Reference Gallery:
Intimal sarcoma. CT of a patient with intimal sarcoma of the right pulmonary artery demonstrating a solid intraluminal mass, which showed metabolic activity on PET-CT (not pictured).
Intimal sarcoma. Spreading of the tumour along the intrapulmonary branches of the pulmonary artery.
Intimal sarcoma. View of the hilum of the resected lung of a patient with obstruction of the lumen of the pulmonary artery by tumour tissue.
Intimal sarcoma. Endarterectomy specimen of another patient with intimal sarcoma of the pulmonary artery.
Intimal sarcoma. Myxoid tumour with low cellular density.
Intimal sarcoma. Bundles of tumour cells resembling leiomyosarcoma.
Intimal sarcoma. An endothelium-lined vascular cleft surrounded by pleomorphic tumour cells.
Intimal sarcoma. Nuclear immunoexpression of MDM2 protein in numerous tumour cells.
Intimal sarcoma. A representative copy-number alteration profile (Agilent 244K array comparative genomic hybridization) showing high-level amplification of the PDGFRA/4q12 and MDM2/12q14-q15 regions; gain of 6q, 7, 8q, 12p, and 17q; and partial/total losses of 1p, 3q, 5q, 9p, 10, 15q, 18, and X. The individual probes are arranged according to their genomic location (x axis) and their respective tumour/reference log2 ratios (y axis). B Array comparative genomic hybridization profile of a selected region of chromosome band 4q12, showing high-level amplification of the genes CHIC2, PDGFRA, and KIT. C A representative example of dual-colour interphase FISH images of intimal sarcoma, showing exclusive high-level amplification of PDGFRA (red signals; long arrows) or MDM2 (green signals; short arrows), intermingled with cells showing separate amplicons for both genes.

Q: Li-Fraumeni Syndrome is an inherited cancer predisposition syndrome characterized by a broad spectrum of early-onset tumors (e.g., breast cancer, osteosarcomas, adrenocortical tumors) and is definitively diagnosed by identifying germline mutations in the [...] gene.
Percentage distribution of 2095 tumours associated with TP53 germline mutations, by anatomical site (adapted from the IARC TP53 Database)
Percentage distribution of 1219 TP53 germline mutations by mutation type
A: TP53
Back Extra: Li-Fraumeni Syndrome
- Clinical: Li-Fraumeni Syndrome is characterized by early onset of a broad spectrum of cancers, with a high lifetime cancer risk. Common tumours include breast cancer, soft tissue sarcomas, brain tumours, osteosarcomas, and adrenocortical tumours.
- Micro: The tumours in Li-Fraumeni Syndrome patients have no distinct histopathological features from their sporadic counterparts. However, p53 immunostaining often shows intense nuclear staining in tumour cells.
- Ancillary: TP53 is the only gene definitively associated with cancer risk in Li-Fraumeni Syndrome and is considered diagnostic. Variants of uncertain significance are sometimes found but their role is controversial.
Reference Gallery:
Percentage distribution of 2095 tumours associated with TP53 germline mutations, by anatomical site (adapted from the IARC TP53 Database)
Percentage distribution of 1219 TP53 germline mutations by mutation type

Q: Characteristic clinical manifestations of Neurofibromatosis Type 1 include axillary/inguinal freckling, cutaneous neurofibromas, and multiple [...].
Neurofibromatosis type 1. Multiple café-au-lait spots on the back.
Neurofibromatosis type 1. Cutaneous neurofibromas.
A: café-au-lait spots
Back Extra: Neurofibromatosis Type 1
- Clinical: Multiple café-au-lait spots, axillary/inguinal freckling, Lisch nodules, and optic pathway gliomas are characteristic manifestations of Neurofibromatosis Type 1.
- Micro: The histopathology of tumours in Neurofibromatosis Type 1 is similar to their sporadic counterparts.
- Ancillary: A pathogenic NF1 mutation is detected in up to 95% of individuals with Neurofibromatosis Type 1, and a second hit in NF1 can be found in associated tumours.
Reference Gallery:
Neurofibromatosis type 1. Multiple café-au-lait spots on the back.
Neurofibromatosis type 1. Cutaneous neurofibromas.
Neurofibromatosis type 1. The function of neurofibromin (NF1) in the RAS/MAPK pathway. ERK, extracellular signal–regulated kinase; MEK, MAPK kinase.

Q: A pathogenic mutation in the NF1 gene is detected in up to 95% of individuals with Neurofibromatosis Type 1, resulting in loss of neurofibromin function and dysregulation of the [...] signaling pathway.
Neurofibromatosis type 1. The function of neurofibromin (NF1) in the RAS/MAPK pathway. ERK, extracellular signal–regulated kinase; MEK, MAPK kinase.
A: RAS/MAPK
Back Extra: Neurofibromatosis Type 1
- Clinical: Multiple café-au-lait spots, axillary/inguinal freckling, Lisch nodules, and optic pathway gliomas are characteristic manifestations of Neurofibromatosis Type 1.
- Micro: The histopathology of tumours in Neurofibromatosis Type 1 is similar to their sporadic counterparts.
- Ancillary: A pathogenic NF1 mutation is detected in up to 95% of individuals with Neurofibromatosis Type 1, and a second hit in NF1 can be found in associated tumours.
Reference Gallery:
Neurofibromatosis type 1. Multiple café-au-lait spots on the back.
Neurofibromatosis type 1. Cutaneous neurofibromas.
Neurofibromatosis type 1. The function of neurofibromin (NF1) in the RAS/MAPK pathway. ERK, extracellular signal–regulated kinase; MEK, MAPK kinase.

Q: The hallmark cutaneous feature of Rothmund–Thomson Syndrome, characterized clinically by a marbleized mix of hypopigmentation, hyperpigmentation, telangiectasia, and skin atrophy, is [...].
Rothmund–Thomson syndrome. Poikiloderma. Extensor surface of lower leg demonstrating the chronic phase with skin atrophy, marbleized mixed hypopigmentation, and hyperpigmentation with telangiectasia.
Rothmund–Thomson syndrome. Histopathological features of poikiloderma characteristically seen in Rothmund–Thomson syndrome, with prominent superficial dermal vessels, minimal basal cell vacuolization, and intraepidermal dyskeratotic cells.
A: poikiloderma
Back Extra: Rothmund–Thomson Syndrome
- Clinical: The hallmark of Rothmund–Thomson Syndrome is poikiloderma, characterized by reticulated hypopigmentation and hyperpigmentation, telangiectasia, and atrophy.
- Micro: Histological features include hyperkeratosis, epidermal atrophy, intraepidermal dyskeratotic cells, basal cell vacuolization, and melanin incontinence.
- Ancillary: Molecular testing for biallelic pathogenic variants in the RECQL4 gene confirms a diagnosis of RTS type 2.
Reference Gallery:
Rothmund–Thomson syndrome. Poikiloderma. Extensor surface of lower leg demonstrating the chronic phase with skin atrophy, marbleized mixed hypopigmentation, and hyperpigmentation with telangiectasia.
Rothmund–Thomson syndrome. Radial ray defect manifest as missing thumb.
Rothmund–Thomson syndrome. Histopathological features of poikiloderma characteristically seen in Rothmund–Thomson syndrome, with prominent superficial dermal vessels, minimal basal cell vacuolization, and intraepidermal dyskeratotic cells.
Rothmund–Thomson syndrome. Osteoblastic osteosarcoma, the most common malignancy seen in Rothmund–Thomson syndrome, displays pleomorphic osteoblasts and eosinophilic malignant osteoid.

Q: Rothmund–Thomson Syndrome type 2 is confirmed by biallelic pathogenic variants in the RECQL4 gene and carries a significantly increased risk for developing [...], which histologically displays pleomorphic malignant cells producing eosinophilic osteoid.
Rothmund–Thomson syndrome. Osteoblastic osteosarcoma, the most common malignancy seen in Rothmund–Thomson syndrome, displays pleomorphic osteoblasts and eosinophilic malignant osteoid.
A: osteosarcoma
Back Extra: Rothmund–Thomson Syndrome
- Clinical: The hallmark of Rothmund–Thomson Syndrome is poikiloderma, characterized by reticulated hypopigmentation and hyperpigmentation, telangiectasia, and atrophy.
- Micro: Histological features include hyperkeratosis, epidermal atrophy, intraepidermal dyskeratotic cells, basal cell vacuolization, and melanin incontinence.
- Ancillary: Molecular testing for biallelic pathogenic variants in the RECQL4 gene confirms a diagnosis of RTS type 2.
Reference Gallery:
Rothmund–Thomson syndrome. Poikiloderma. Extensor surface of lower leg demonstrating the chronic phase with skin atrophy, marbleized mixed hypopigmentation, and hyperpigmentation with telangiectasia.
Rothmund–Thomson syndrome. Radial ray defect manifest as missing thumb.
Rothmund–Thomson syndrome. Histopathological features of poikiloderma characteristically seen in Rothmund–Thomson syndrome, with prominent superficial dermal vessels, minimal basal cell vacuolization, and intraepidermal dyskeratotic cells.
Rothmund–Thomson syndrome. Osteoblastic osteosarcoma, the most common malignancy seen in Rothmund–Thomson syndrome, displays pleomorphic osteoblasts and eosinophilic malignant osteoid.

Q: Along with characteristic skin changes, patients with Rothmund–Thomson Syndrome frequently present with skeletal anomalies, most notably a [...] defect manifesting as an absent or hypoplastic thumb.
Rothmund–Thomson syndrome. Radial ray defect manifest as missing thumb.
A: radial ray
Back Extra: Rothmund–Thomson Syndrome
- Clinical: The hallmark of Rothmund–Thomson Syndrome is poikiloderma, characterized by reticulated hypopigmentation and hyperpigmentation, telangiectasia, and atrophy.
- Micro: Histological features include hyperkeratosis, epidermal atrophy, intraepidermal dyskeratotic cells, basal cell vacuolization, and melanin incontinence.
- Ancillary: Molecular testing for biallelic pathogenic variants in the RECQL4 gene confirms a diagnosis of RTS type 2.
Reference Gallery:
Rothmund–Thomson syndrome. Poikiloderma. Extensor surface of lower leg demonstrating the chronic phase with skin atrophy, marbleized mixed hypopigmentation, and hyperpigmentation with telangiectasia.
Rothmund–Thomson syndrome. Radial ray defect manifest as missing thumb.
Rothmund–Thomson syndrome. Histopathological features of poikiloderma characteristically seen in Rothmund–Thomson syndrome, with prominent superficial dermal vessels, minimal basal cell vacuolization, and intraepidermal dyskeratotic cells.
Rothmund–Thomson syndrome. Osteoblastic osteosarcoma, the most common malignancy seen in Rothmund–Thomson syndrome, displays pleomorphic osteoblasts and eosinophilic malignant osteoid.

Q: McCune-Albright Syndrome is classically characterized by a triad of fibrous dysplasia, hyperfunctioning endocrinopathies (such as precocious puberty), and irregular, large skin lesions known as [...].
McCune–Albright syndrome. A photograph of a child with café-au-lait macules demonstrating typical features, including jagged borders and location reflecting along the midline of the body.
McCune–Albright syndrome. A femoral radiograph shows diffuse involvement with fibrous dysplasia. Note the homogeneous ground-glass radiolucency and lack of defined cortices. Bowing of the proximal femur has resulted in a coxa vara (shepherd’s crook) deformity.
A: café-au-lait macules
Back Extra: McCune-Albright Syndrome
- Clinical: McCune-Albright Syndrome is characterized by the triad of fibrous dysplasia, café-au-lait skin lesions, and hyperfunctioning endocrinopathies, including precocious puberty and hyperthyroidism.
- Micro: Fibrous dysplasia lesions show replacement of normal bone and marrow with fibrous tissue and poorly mineralized woven bone, often with high vascularity and venous pooling.
- Ancillary: The molecular basis of McCune-Albright Syndrome is a postzygotic somatic mutation in exon 8 of GNAS, leading to constitutive activation of the stimulatory G protein (Gsα) and increased cAMP production.
Reference Gallery:
McCune–Albright syndrome. A photograph of a child with café-au-lait macules demonstrating typical features, including jagged borders and location reflecting along the midline of the body.
McCune–Albright syndrome. A femoral radiograph shows diffuse involvement with fibrous dysplasia. Note the homogeneous ground-glass radiolucency and lack of defined cortices. Bowing of the proximal femur has resulted in a coxa vara (shepherd’s crook) deformity.
McCune–Albright syndrome. Testicular ultrasound shows extensive hyperechoic and hypoechoic lesions (blue arrows).
McCune–Albright syndrome. CT shows fibrous dysplasia involving the left side of the mandible. Note the expansile lesions with a homogeneous ground-glass appearance (red arrow).
Fibrous dysplasia. A Masson-stained section taken from an iliac crest shows characteristic discontinuous trabeculae interspersed with fibrous tissue.
McCune–Albright syndrome. A Activating mutations (p.Arg201Cys or p.Arg201His) in the gene encoding the α subunit of stimulatory G protein (Gs) abrogate the endogenous GTPase of the α subunit, leading to ligand-independent stimulation of adenylyl cyclase. The PKA or cAMP-dependent protein kinase pathway is shown on the right. The PKC pathway is shown on the left. The inability to hydrolyse GTP leads to persistent binding of Gsα to adenylyl cyclase and continuous synthesis of cAMP, which in turn overactivates the PKA pathway. PKA is composed of two regulatory subunits (RS), which have binding sites for cAMP, and two catalytic subunits (CS) that, when dissociated, phosphorylate serine/threonine kinases (STK). The dissociated βγ subunits of Gs overactivate the PKC pathway. Phospholipase C (PLC) cleaves PIP2 into two intracellular messengers: diacylglycerol (DAG) and inositol trisphosphate (IP3). The latter triggers the release of sequestered calcium ions (Ca2+), which together with DAG activate PKC. B Normally, the hydrolysis of GTP associated with Gsα leads to dissociation of Gsα-GDP from adenylyl cyclase and reassociation with the βγ dimer to form the inactive heterotrimer. Ligand binding causes repetition of the cycle.
Fibrous dysplasia. A high-power view of part of the area denoted by the box in <<#6600>>Fig. #6600 demonstrates typical features, including replacement of normal marrow structures with fibrous tissue (FT), representing proliferation of fibroblast-like bone marrow stromal cells, and woven bone (WB), which is poorly mineralized with prominent osteoid (O). Arrays of collagen bundles (Sharpey fibres) are oriented perpendicularly to the osteoid. Note the high degree of vascularity with venous pooling (V).

Q: The molecular pathogenesis of McCune-Albright Syndrome involves a postzygotic somatic mutation in the [...] gene, which leads to constitutive activation of the stimulatory G protein (Gsα) and excessive cAMP production.
McCune–Albright syndrome. A Activating mutations (p.Arg201Cys or p.Arg201His) in the gene encoding the α subunit of stimulatory G protein (Gs) abrogate the endogenous GTPase of the α subunit, leading to ligand-independent stimulation of adenylyl cyclase. The PKA or cAMP-dependent protein kinase pathway is shown on the right. The PKC pathway is shown on the left. The inability to hydrolyse GTP leads to persistent binding of Gsα to adenylyl cyclase and continuous synthesis of cAMP, which in turn overactivates the PKA pathway. PKA is composed of two regulatory subunits (RS), which have binding sites for cAMP, and two catalytic subunits (CS) that, when dissociated, phosphorylate serine/threonine kinases (STK). The dissociated βγ subunits of Gs overactivate the PKC pathway. Phospholipase C (PLC) cleaves PIP2 into two intracellular messengers: diacylglycerol (DAG) and inositol trisphosphate (IP3). The latter triggers the release of sequestered calcium ions (Ca2+), which together with DAG activate PKC. B Normally, the hydrolysis of GTP associated with Gsα leads to dissociation of Gsα-GDP from adenylyl cyclase and reassociation with the βγ dimer to form the inactive heterotrimer. Ligand binding causes repetition of the cycle.
A: GNAS
Back Extra: McCune-Albright Syndrome
- Clinical: McCune-Albright Syndrome is characterized by the triad of fibrous dysplasia, café-au-lait skin lesions, and hyperfunctioning endocrinopathies, including precocious puberty and hyperthyroidism.
- Micro: Fibrous dysplasia lesions show replacement of normal bone and marrow with fibrous tissue and poorly mineralized woven bone, often with high vascularity and venous pooling.
- Ancillary: The molecular basis of McCune-Albright Syndrome is a postzygotic somatic mutation in exon 8 of GNAS, leading to constitutive activation of the stimulatory G protein (Gsα) and increased cAMP production.
Reference Gallery:
McCune–Albright syndrome. A photograph of a child with café-au-lait macules demonstrating typical features, including jagged borders and location reflecting along the midline of the body.
McCune–Albright syndrome. A femoral radiograph shows diffuse involvement with fibrous dysplasia. Note the homogeneous ground-glass radiolucency and lack of defined cortices. Bowing of the proximal femur has resulted in a coxa vara (shepherd’s crook) deformity.
McCune–Albright syndrome. Testicular ultrasound shows extensive hyperechoic and hypoechoic lesions (blue arrows).
McCune–Albright syndrome. CT shows fibrous dysplasia involving the left side of the mandible. Note the expansile lesions with a homogeneous ground-glass appearance (red arrow).
Fibrous dysplasia. A Masson-stained section taken from an iliac crest shows characteristic discontinuous trabeculae interspersed with fibrous tissue.
McCune–Albright syndrome. A Activating mutations (p.Arg201Cys or p.Arg201His) in the gene encoding the α subunit of stimulatory G protein (Gs) abrogate the endogenous GTPase of the α subunit, leading to ligand-independent stimulation of adenylyl cyclase. The PKA or cAMP-dependent protein kinase pathway is shown on the right. The PKC pathway is shown on the left. The inability to hydrolyse GTP leads to persistent binding of Gsα to adenylyl cyclase and continuous synthesis of cAMP, which in turn overactivates the PKA pathway. PKA is composed of two regulatory subunits (RS), which have binding sites for cAMP, and two catalytic subunits (CS) that, when dissociated, phosphorylate serine/threonine kinases (STK). The dissociated βγ subunits of Gs overactivate the PKC pathway. Phospholipase C (PLC) cleaves PIP2 into two intracellular messengers: diacylglycerol (DAG) and inositol trisphosphate (IP3). The latter triggers the release of sequestered calcium ions (Ca2+), which together with DAG activate PKC. B Normally, the hydrolysis of GTP associated with Gsα leads to dissociation of Gsα-GDP from adenylyl cyclase and reassociation with the βγ dimer to form the inactive heterotrimer. Ligand binding causes repetition of the cycle.
Fibrous dysplasia. A high-power view of part of the area denoted by the box in <<#6600>>Fig. #6600 demonstrates typical features, including replacement of normal marrow structures with fibrous tissue (FT), representing proliferation of fibroblast-like bone marrow stromal cells, and woven bone (WB), which is poorly mineralized with prominent osteoid (O). Arrays of collagen bundles (Sharpey fibres) are oriented perpendicularly to the osteoid. Note the high degree of vascularity with venous pooling (V).

Q: In McCune-Albright Syndrome, the characteristic fibrous dysplasia lesions microscopically demonstrate the replacement of normal marrow with fibrous tissue and irregular, discontinuous trabeculae of poorly mineralized [...].
Fibrous dysplasia. A Masson-stained section taken from an iliac crest shows characteristic discontinuous trabeculae interspersed with fibrous tissue.
Fibrous dysplasia. A high-power view of part of the area denoted by the box in <<#6600>>Fig. #6600 demonstrates typical features, including replacement of normal marrow structures with fibrous tissue (FT), representing proliferation of fibroblast-like bone marrow stromal cells, and woven bone (WB), which is poorly mineralized with prominent osteoid (O). Arrays of collagen bundles (Sharpey fibres) are oriented perpendicularly to the osteoid. Note the high degree of vascularity with venous pooling (V).
A: woven bone
Back Extra: McCune-Albright Syndrome
- Clinical: McCune-Albright Syndrome is characterized by the triad of fibrous dysplasia, café-au-lait skin lesions, and hyperfunctioning endocrinopathies, including precocious puberty and hyperthyroidism.
- Micro: Fibrous dysplasia lesions show replacement of normal bone and marrow with fibrous tissue and poorly mineralized woven bone, often with high vascularity and venous pooling.
- Ancillary: The molecular basis of McCune-Albright Syndrome is a postzygotic somatic mutation in exon 8 of GNAS, leading to constitutive activation of the stimulatory G protein (Gsα) and increased cAMP production.
Reference Gallery:
McCune–Albright syndrome. A photograph of a child with café-au-lait macules demonstrating typical features, including jagged borders and location reflecting along the midline of the body.
McCune–Albright syndrome. A femoral radiograph shows diffuse involvement with fibrous dysplasia. Note the homogeneous ground-glass radiolucency and lack of defined cortices. Bowing of the proximal femur has resulted in a coxa vara (shepherd’s crook) deformity.
McCune–Albright syndrome. Testicular ultrasound shows extensive hyperechoic and hypoechoic lesions (blue arrows).
McCune–Albright syndrome. CT shows fibrous dysplasia involving the left side of the mandible. Note the expansile lesions with a homogeneous ground-glass appearance (red arrow).
Fibrous dysplasia. A Masson-stained section taken from an iliac crest shows characteristic discontinuous trabeculae interspersed with fibrous tissue.
McCune–Albright syndrome. A Activating mutations (p.Arg201Cys or p.Arg201His) in the gene encoding the α subunit of stimulatory G protein (Gs) abrogate the endogenous GTPase of the α subunit, leading to ligand-independent stimulation of adenylyl cyclase. The PKA or cAMP-dependent protein kinase pathway is shown on the right. The PKC pathway is shown on the left. The inability to hydrolyse GTP leads to persistent binding of Gsα to adenylyl cyclase and continuous synthesis of cAMP, which in turn overactivates the PKA pathway. PKA is composed of two regulatory subunits (RS), which have binding sites for cAMP, and two catalytic subunits (CS) that, when dissociated, phosphorylate serine/threonine kinases (STK). The dissociated βγ subunits of Gs overactivate the PKC pathway. Phospholipase C (PLC) cleaves PIP2 into two intracellular messengers: diacylglycerol (DAG) and inositol trisphosphate (IP3). The latter triggers the release of sequestered calcium ions (Ca2+), which together with DAG activate PKC. B Normally, the hydrolysis of GTP associated with Gsα leads to dissociation of Gsα-GDP from adenylyl cyclase and reassociation with the βγ dimer to form the inactive heterotrimer. Ligand binding causes repetition of the cycle.
Fibrous dysplasia. A high-power view of part of the area denoted by the box in <<#6600>>Fig. #6600 demonstrates typical features, including replacement of normal marrow structures with fibrous tissue (FT), representing proliferation of fibroblast-like bone marrow stromal cells, and woven bone (WB), which is poorly mineralized with prominent osteoid (O). Arrays of collagen bundles (Sharpey fibres) are oriented perpendicularly to the osteoid. Note the high degree of vascularity with venous pooling (V).

Q: Over 90% of patients with Multiple Osteochondromas harbor germline mutations in the [...] genes.
Multiple osteochondromas. Genomic structure of the EXT1 and EXT2 genes. The grey boxes represent coding regions. The mutation spectrum for each gene is illustrated below the genomic structure to include the frequency of exon involvement.
A: EXT1 or EXT2
Back Extra: Multiple Osteochondromas
- Clinical: Osteochondromas develop and increase in size during the first two decades of life, ceasing to grow when the growth plates close at the end of puberty. They can cause orthopaedic deformities, pain, and rarely, malignant transformation.
- Micro: Histopathologically identical to sporadic osteochondromas. Malignant transformation leads to secondary peripheral ACT/CS1 in the vast majority of cases. High-grade chondrosarcoma is rare.
- Ancillary: Germline mutations in EXT1 or EXT2 are detected in >90% of patients. Annual MRI screening of affected bones, especially between 20 and 40 years of age, is beneficial.
Reference Gallery:
Multiple osteochondromas. X-ray showing multiple osteochondromas.
Multiple osteochondromas. Genomic structure of the EXT1 and EXT2 genes. The grey boxes represent coding regions. The mutation spectrum for each gene is illustrated below the genomic structure to include the frequency of exon involvement.

Q: The bone lesions seen on X-ray in Multiple Osteochondromas typically cease growing upon closure of the [...] at the end of puberty.
Multiple osteochondromas. X-ray showing multiple osteochondromas.
A: growth plates
Back Extra: Multiple Osteochondromas
- Clinical: Osteochondromas develop and increase in size during the first two decades of life, ceasing to grow when the growth plates close at the end of puberty. They can cause orthopaedic deformities, pain, and rarely, malignant transformation.
- Micro: Histopathologically identical to sporadic osteochondromas. Malignant transformation leads to secondary peripheral ACT/CS1 in the vast majority of cases. High-grade chondrosarcoma is rare.
- Ancillary: Germline mutations in EXT1 or EXT2 are detected in >90% of patients. Annual MRI screening of affected bones, especially between 20 and 40 years of age, is beneficial.
Reference Gallery:
Multiple osteochondromas. X-ray showing multiple osteochondromas.
Multiple osteochondromas. Genomic structure of the EXT1 and EXT2 genes. The grey boxes represent coding regions. The mutation spectrum for each gene is illustrated below the genomic structure to include the frequency of exon involvement.