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10. Pathology and Oncology MCQs

Practice Set 214 of 351

This practice set contains high-yield board review questions covering key concepts in 10. Pathology and Oncology. Each clinical scenario is designed to test your diagnostic and management skills relevant to this subspecialty.

Question 4261

Topic: 10. Pathology and Oncology

A 14-year-old girl presents with knee pain. MRI reveals an eccentric, expansile metaphyseal lesion in the proximal tibia with multiple fluid-fluid levels. Biopsy reveals blood-filled spaces separated by fibrous septa lacking an endothelial lining. Recent molecular studies indicate that primary forms of this lesion are true neoplasms driven by a specific genetic rearrangement. Which gene is most commonly rearranged in this condition?

. USP6
. GNAS
. EXT1
. MDM2
. IDH1

Correct Answer & Explanation

. USP6

Explanation

The lesion described is an aneurysmal bone cyst (ABC). While historically considered a reactive process, molecular analysis has shown that primary ABCs are true neoplasms characterized by translocations involving the USP6 gene (most commonly t(16;17)(q22;p13) producing a CDH11-USP6 fusion). This leads to USP6 upregulation, driving matrix metalloproteinase production and cystic changes. GNAS is seen in fibrous dysplasia; EXT1 in MHE; MDM2 in parosteal osteosarcoma/atypical lipomatous tumors; IDH1 in enchondromas/chondrosarcomas.

Question 4262

Topic: 10. Pathology and Oncology

A 16-year-old boy presents with rapid swelling and pain in his distal femur. MRI reveals an expansile, destructive, predominantly cystic mass with multiple fluid-fluid levels. Based on imaging alone, it closely mimics an aneurysmal bone cyst (ABC). Which of the following histopathological findings differentiates this lesion from a primary ABC?

. The presence of multinucleated giant cells
. Blood-filled spaces lacking endothelial lining
. Highly pleomorphic cells producing delicate lace-like osteoid within the septa
. A thick rim of reactive lamellar bone surrounding the cyst
. Translocation involving the USP6 gene

Correct Answer & Explanation

. Highly pleomorphic cells producing delicate lace-like osteoid within the septa

Explanation

The lesion describes a telangiectatic osteosarcoma, a highly malignant variant of osteosarcoma that classically mimics an ABC radiographically and macroscopically (both have large blood-filled spaces and fluid-fluid levels). The critical differentiating feature on histopathology is the presence of highly atypical, pleomorphic sarcomatous cells producing malignant osteoid within the septae separating the cystic spaces. Primary ABCs lack this cytological atypia and malignant osteoid.

Question 4263

Topic: 10. Pathology and Oncology

A 15-year-old male presents with chronic knee pain. Radiographs reveal a sharply demarcated, 2-cm lytic lesion in the distal femoral epiphysis with a thin sclerotic rim. Histological examination shows mononuclear cells with grooved (coffee-bean) nuclei and scattered multinucleated giant cells. A fine, 'chicken-wire' pattern of pericellular calcification is present. What is the standard treatment for this lesion?

. Wide en bloc resection
. Neoadjuvant chemotherapy followed by limb salvage surgery
. Extended curettage and bone grafting
. Radiation therapy alone
. Indomethacin therapy and observation

Correct Answer & Explanation

. Extended curettage and bone grafting

Explanation

The clinical and histological findings (epiphyseal location in a skeletally immature patient, grooved nuclei, chicken-wire calcification) are diagnostic of a chondroblastoma. It is a benign but locally aggressive cartilage tumor. Standard treatment is extended (aggressive) intralesional curettage (often with high-speed burr and chemical adjuvants like phenol or cryotherapy) followed by bone grafting or PMMA cementing to prevent local recurrence while preserving joint function.

Question 4264

Topic: 10. Pathology and Oncology

A 35-year-old female presents with chronic, painless swelling of the right knee. Aspiration yields dark brown, non-clotting fluid. MRI demonstrates a large, nodular intra-articular soft tissue mass with marked 'blooming artifact' on gradient-echo sequences. This condition is driven by a translocation that results in the overexpression of which of the following?

. Vascular Endothelial Growth Factor (VEGF)
. Colony Stimulating Factor 1 (CSF1)
. Fibroblast Growth Factor Receptor (FGFR)
. Epidermal Growth Factor Receptor (EGFR)
. Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)

Correct Answer & Explanation

. Colony Stimulating Factor 1 (CSF1)

Explanation

The clinical picture and MRI findings (blooming artifact representing hemosiderin deposition) are characteristic of Pigmented Villonodular Synovitis (PVNS), now more accurately termed diffuse tenosynovial giant cell tumor (TGCT). The pathogenesis involves a specific translocation t(1;2) resulting in the fusion of the COL6A3 promoter to the CSF1 gene. This leads to the overexpression and secretion of CSF1 by a small minority of neoplastic cells, which then recruits a massive non-neoplastic inflammatory infiltrate of macrophages expressing the CSF1 receptor. Systemic therapy with CSF1R inhibitors (e.g., pexidartinib) targets this mechanism.

Question 4265

Topic: 10. Pathology and Oncology

A 5-year-old boy presents with anterior bowing of the tibia. Radiographs show a multi-loculated, entirely intracortical lytic lesion along the anterior tibial diaphysis. Biopsy reveals a fibro-osseous lesion with trabeculae of woven bone rimmed by active osteoblasts. Immunohistochemical stains reveal scattered individual cytokeratin-positive cells. What is the most appropriate management for this lesion if it is asymptomatic?

. Immediate wide local excision to prevent malignant transformation
. Amputation due to aggressive local invasion
. Observation with serial radiographs
. Neoadjuvant chemotherapy followed by resection
. Curettage and autologous bone grafting immediately

Correct Answer & Explanation

. Observation with serial radiographs

Explanation

The diagnosis is osteofibrous dysplasia (OFD) of the tibia (Campanacci disease). It occurs almost exclusively in the anterior cortex of the tibia in children <10 years old. Histologically, it features woven bone rimmed by active osteoblasts (unlike fibrous dysplasia, which lacks osteoblastic rimming). A key feature is the presence of scattered cytokeratin-positive cells. OFD shares clinical and histological overlap with adamantinoma but behaves benignly. Asymptomatic lesions are observed, as they often stabilize or spontaneously regress after skeletal maturity. Surgery is reserved for severe deformity or risk of fracture, and is generally delayed until after skeletal maturity due to a high recurrence rate if excised early.

Question 4266

Topic: 10. Pathology and Oncology

A 32-year-old male presents with chronic, dull anterior shin pain. Radiographs demonstrate an eccentric, multi-loculated, "soap-bubble" osteolytic lesion in the anterior tibial diaphysis. Biopsy reveals a biphasic tumor characterized by nests of basaloid cells surrounded by a bland fibrous stroma. Immunohistochemistry is strongly positive for cytokeratin and epithelial membrane antigen (EMA).

Which of the following is the most likely diagnosis?

. Osteofibrous dysplasia
. Adamantinoma
. Ewing sarcoma
. Chondromyxoid fibroma
. Synovial sarcoma

Correct Answer & Explanation

. Adamantinoma

Explanation

The clinical presentation and histology are classic for adamantinoma. Adamantinoma is a rare, low-grade malignant bone tumor that almost exclusively occurs in the anterior diaphyseal cortex of the tibia. Histologically, it is a biphasic tumor consisting of epithelial cells (which stain positively for cytokeratin and EMA) interspersed in an osteofibrous stroma. Osteofibrous dysplasia (OFD) occurs in a similar location but typically in the first decade of life and lacks the prominent epithelial nests seen in adamantinoma (though OFD can have scattered cytokeratin-positive cells, it is not grossly biphasic). Standard treatment for adamantinoma is wide en bloc resection, as it is relatively radioresistant and chemoresistant.

Question 4267

Topic: 10. Pathology and Oncology

A 45-year-old male presents with persistent right hip pain. Radiographs demonstrate a well-defined, expansile, lytic lesion in the proximal femoral epiphysis. Biopsy shows large cells with abundant clear cytoplasm, distinct cytoplasmic membranes, and centrally located nuclei, admixed with areas of conventional hyaline cartilage. Which of the following is the most accurate statement regarding this condition?

. It typically presents as a diaphyseal lesion in young children.
. It has a distinct predilection for the epiphysis of long bones.
. It is best managed with primary external beam radiation therapy.
. A characteristic t(X;18) chromosomal translocation is pathognomonic.
. It represents the malignant transformation of a pre-existing chondroblastoma.

Correct Answer & Explanation

. It has a distinct predilection for the epiphysis of long bones.

Explanation

The diagnosis is clear cell chondrosarcoma. This is a rare, low-grade variant of chondrosarcoma that is unique among malignant bone tumors because it has a strong predilection for the epiphyses of long bones (most commonly the proximal femur and proximal humerus) in adults (typically 30-50 years old). This distinguishes it from conventional chondrosarcoma (which is usually metaphyseal/diaphyseal) and chondroblastoma (which is epiphyseal but typically occurs in skeletally immature patients). Wide surgical resection is the treatment of choice. t(X;18) is seen in synovial sarcoma. It is distinct from chondroblastoma and does not arise from it.

Question 4268

Topic: 10. Pathology and Oncology

A 48-year-old female with a known history of polyostotic fibrous dysplasia presents with a painless, slow-growing soft tissue mass in her right thigh. MRI reveals a well-circumscribed intramuscular mass exhibiting high T2 signal and heterogeneous contrast enhancement. A biopsy confirms an intramuscular myxoma.

What is the underlying genetic mutation associated with this specific syndrome?

. Loss-of-function mutation in the PTEN gene
. Missense mutation in the GNAS gene
. Inactivating mutation in EXT1
. Deletion of the NF1 gene
. Loss of heterozygosity in RB1

Correct Answer & Explanation

. Missense mutation in the GNAS gene

Explanation

The patient's presentation of polyostotic fibrous dysplasia combined with intramuscular myxomas is diagnostic of Mazabraud syndrome. Like isolated fibrous dysplasia and McCune-Albright syndrome, Mazabraud syndrome is caused by an activating post-zygotic missense mutation in the GNAS gene (specifically at the Arg201 codon). This mutation leads to constitutive activation of the Gs-alpha protein and downstream overproduction of cAMP, which disrupts normal osteoblast differentiation and promotes the formation of fibro-osseous lesions and myxomas.

Question 4269

Topic: 10. Pathology and Oncology

A 14-year-old girl presents with multiple asymmetric cartilaginous bone lesions leading to limb length discrepancy, along with several bluish soft-tissue nodules on her hands and feet. A biopsy of a soft-tissue nodule reveals a spindle cell hemangioma. Which of the following statements is true regarding her condition compared to a patient with multiple enchondromas alone (Ollier disease)?

. She has a significantly higher risk of developing non-mesenchymal malignancies, such as astrocytoma or ovarian carcinoma.
. Her condition is inherited in an autosomal dominant pattern with high penetrance.
. She has a lower lifetime risk of malignant transformation to chondrosarcoma.
. Her condition is characterized by a pathognomonic t(11;22) chromosomal translocation.
. She is more likely to experience spontaneous resolution of her bone lesions after skeletal maturity.

Correct Answer & Explanation

. She has a significantly higher risk of developing non-mesenchymal malignancies, such as astrocytoma or ovarian carcinoma.

Explanation

The patient has Maffucci syndrome, characterized by multiple enchondromas and soft tissue hemangiomas (often spindle cell hemangiomas). While both Ollier disease (enchondromatosis alone) and Maffucci syndrome carry a high risk of malignant transformation to chondrosarcoma (estimated up to 25-30% for Ollier and closer to 100% lifetime risk for Maffucci), Maffucci syndrome is uniquely associated with a high risk of developing secondary non-mesenchymal malignancies, such as astrocytomas, gastrointestinal carcinomas, and ovarian tumors. Both disorders are caused by somatic mosaic mutations in IDH1 or IDH2, not inherited autosomal dominant mutations.

Question 4270

Topic: 10. Pathology and Oncology

A 12-year-old boy presents with an expansile, lytic, multi-cystic lesion in the distal femoral metaphysis. MRI demonstrates multiple fluid-fluid levels within the lesion. A core needle biopsy confirms a primary aneurysmal bone cyst (ABC).

Which of the following molecular alterations is most characteristic and diagnostic of a primary aneurysmal bone cyst?

. USP6 gene rearrangement [t(16;17)]
. GNAS missense mutation
. MDM2 and CDK4 amplification
. t(X;18) chromosomal translocation
. BRAF V600E somatic mutation

Correct Answer & Explanation

. USP6 gene rearrangement [t(16;17)]

Explanation

Primary Aneurysmal Bone Cysts (ABCs) are now recognized as genuine neoplasms rather than purely reactive lesions. They are driven by a characteristic recurrent chromosomal translocation, t(16;17)(q22;p13), which results in the upregulation of the USP6 gene (ubiquitin-specific protease 6). This helps distinguish primary ABCs from secondary ABCs, which can arise in the setting of other tumors (e.g., giant cell tumor, osteoblastoma, chondroblastoma) and lack the USP6 rearrangement. GNAS is seen in fibrous dysplasia; MDM2 in atypical lipomatous tumors and parosteal osteosarcoma; t(X;18) in synovial sarcoma; and BRAF V600E in Langerhans Cell Histiocytosis.

Question 4271

Topic: 10. Pathology and Oncology

A 25-year-old male undergoes curettage of a locally aggressive lytic lesion in the mandible. Histological examination reveals an abundant collagenous stroma containing uniform, spindled fibroblasts with no cytologic atypia, pleomorphism, or necrosis. Immunohistochemistry demonstrates abnormal nuclear accumulation of beta-catenin. What is the most likely diagnosis?

. Desmoplastic fibroma
. Fibrous dysplasia
. Non-ossifying fibroma
. Low-grade central osteosarcoma
. Chondromyxoid fibroma

Correct Answer & Explanation

. Desmoplastic fibroma

Explanation

Desmoplastic fibroma is a rare, locally aggressive, benign primary bone tumor that is considered the intraosseous equivalent of extra-abdominal soft-tissue desmoid tumors (desmoid-type fibromatosis). Like soft tissue desmoid tumors, desmoplastic fibromas of bone frequently harbor mutations in the CTNNB1 gene or APC gene, leading to the abnormal nuclear accumulation of beta-catenin. Histologically, it features bland fibroblasts separated by abundant collagen without atypia or matrix calcification. Treatment involves wide local excision due to the high risk of local recurrence with curettage alone.

Question 4272

Topic: 10. Pathology and Oncology
A 50-year-old male presents with generalized progressive muscle weakness, diffuse bone pain, and multiple pseudo-fractures visible on radiographs. Laboratory studies reveal severe hypophosphatemia, decreased 1,25-dihydroxyvitamin D, and normal serum calcium levels. A total body DOTATATE PET/CT reveals a small, highly avid soft tissue mass in the plantar aspect of the left foot. Surgical resection of this mass will most likely demonstrate a neoplasm secreting which of the following?
. Parathyroid hormone (PTH)
. Parathyroid hormone-related peptide (PTHrP)
. Fibroblast Growth Factor 23 (FGF23)
. 1,25-dihydroxyvitamin D
. Calcitonin

Correct Answer & Explanation

. Fibroblast Growth Factor 23 (FGF23)

Explanation

The patient's presentation is pathognomonic for Tumor-Induced Osteomalacia (TIO), also known as oncogenic osteomalacia. TIO is a paraneoplastic syndrome typically caused by a small, benign, indolent mesenchymal tumor (Phosphaturic Mesenchymal Tumor, or PMT) that secretes Fibroblast Growth Factor 23 (FGF23). FGF23 acts on the kidneys to inhibit phosphate reabsorption (causing phosphaturia and hypophosphatemia) and inhibits 1-alpha-hydroxylase (reducing active vitamin D synthesis). Complete surgical resection of the offending tumor typically results in a rapid and complete reversal of the biochemical and clinical abnormalities.

Question 4273

Topic: 10. Pathology and Oncology

A 35-year-old female presents with a 2-year history of chronic lower back pain and new-onset saddle anesthesia. Imaging reveals a well-circumscribed, lytic mass within the sacrum causing cortical expansion. Biopsy shows cuboidal to columnar cells arranged radially around myxoid vascular cores.

Which of the following is the most likely diagnosis?

. Chordoma
. Chondrosarcoma
. Giant cell tumor of bone
. Myxopapillary ependymoma
. Schwannoma

Correct Answer & Explanation

. Myxopapillary ependymoma

Explanation

The description of "cells arranged radially around myxoid vascular cores" characterizes perivascular pseudorosettes, which are the histologic hallmark of a myxopapillary ependymoma. This is a crucial differential diagnosis for sacral and sacrococcygeal masses. While chordoma is the most common primary malignant tumor of the sacrum, its classic histology features cords of vacuolated "physaliferous" cells in a myxoid stroma, not perivascular pseudorosettes. Myxopapillary ependymomas arise from the filum terminale and can present as primary sacral bone lesions through direct extension or primary intraosseous development.

Question 4274

Topic: 10. Pathology and Oncology

A 62-year-old male presents with a pathologic fracture of the proximal femur. Radiographs show an aggressive lytic lesion with cortical destruction superimposed on a background of intralesional stippled and "popcorn" calcifications. Biopsy demonstrates a sharp, distinct histologic transition between a low-grade hyaline cartilage tumor and a high-grade, non-chondrogenic pleomorphic spindle cell sarcoma. Which of the following best characterizes the clinical behavior of this specific lesion?

. Excellent long-term survival with neoadjuvant multi-agent chemotherapy alone.
. Dismal prognosis, with a very high likelihood of early hematogenous metastasis to the lungs.
. Typically arises only in patients with Multiple Hereditary Exostoses (MHE).
. Best managed definitively with intralesional curettage and cementation.
. Lymph node metastasis is its primary and most common route of systemic spread.

Correct Answer & Explanation

. Dismal prognosis, with a very high likelihood of early hematogenous metastasis to the lungs.

Explanation

The clinical and histologic description represents a dedifferentiated chondrosarcoma. This tumor is defined by the coexistence of a well-differentiated, low-grade cartilage tumor abruptly adjacent to a high-grade, non-cartilaginous sarcoma (e.g., osteosarcoma, undifferentiated pleomorphic sarcoma). Dedifferentiated chondrosarcoma is highly aggressive and carries a dismal prognosis, with a 5-year survival rate often reported below 15-20%, primarily due to early and rapid hematogenous dissemination to the lungs. Chemotherapy is generally ineffective for the low-grade chondroid component, though it is sometimes attempted for the high-grade component. Wide surgical resection is required.

Question 4275

Topic: Bone Tumors

A 55-year-old male undergoes en bloc resection of a clival tumor. Histopathology reveals lobulated architecture containing characteristic physaliferous cells with abundant, bubbly, vacuolated cytoplasm embedded in a myxoid stroma. Which of the following immunohistochemical markers is most highly specific for confirming this diagnosis and distinguishing it from a chondrosarcoma?

. S100 protein
. Cytokeratin
. Brachyury
. CD99
. Epithelial Membrane Antigen (EMA)

Correct Answer & Explanation

. Brachyury

Explanation

The lesion described is a chordoma, characterized histologically by physaliferous (bubbly) cells. Differentiating chordoma from chondrosarcoma can sometimes be challenging, particularly in the skull base and spine. Both can be positive for S100. However, Brachyury (a transcription factor crucial for notochord development) is highly sensitive and specific for chordoma and is negative in chondrosarcomas. Chordomas are also typically positive for epithelial markers (Cytokeratin and EMA), whereas conventional chondrosarcomas are negative, but Brachyury is considered the definitive confirmatory marker.

Question 4276

Topic: 10. Pathology and Oncology

A 28-year-old female presents with a painless, hard, fixed mass on the posterior aspect of her distal thigh. Radiographs demonstrate a dense, heavily ossified, lobulated mass originating from the posterior cortex of the distal femur. A distinct radiolucent cleft (the "string sign") separates a portion of the tumor from the underlying diaphyseal cortex.

What is the most characteristic genetic aberration associated with this primary bone tumor?

. MDM2 and CDK4 amplification
. EWSR1-FLI1 fusion
. H3F3A mutation
. EXT1 or EXT2 loss of function
. TP53 mutation alone

Correct Answer & Explanation

. MDM2 and CDK4 amplification

Explanation

The clinical presentation, location (posterior distal femur), and radiographic "string sign" are classic for parosteal osteosarcoma, a low-grade surface osteosarcoma. Molecularly, parosteal osteosarcomas (like low-grade central osteosarcomas and atypical lipomatous tumors) are characterized by supernumerary ring chromosomes containing amplifications of the 12q13-15 region, which prominently houses the MDM2 and CDK4 genes. MDM2 is an antagonist of the p53 tumor suppressor. Identifying MDM2 amplification via FISH is highly useful in distinguishing parosteal osteosarcoma from reactive lesions like myositis ossificans.

Question 4277

Topic: 10. Pathology and Oncology

A 14-year-old boy presents with a destructive diaphyseal lesion in his left fibula associated with a prominent "onion-skin" periosteal reaction. A core biopsy reveals sheets of small, uniform, round blue cells with scant cytoplasm that are diffusely positive for CD99 (MIC2). While the EWSR1-FLI1 fusion via t(11;22) is the most common translocation driving this disease, which of the following represents the second most common fusion gene variant found in this tumor?

. EWSR1-ERG t(21;22)
. SYT-SSX t(X;18)
. ETV6-NTRK3 t(12;15)
. PAX3-FOXO1 t(2;13)
. FUS-DDIT3 t(12;16)

Correct Answer & Explanation

. EWSR1-ERG t(21;22)

Explanation

The patient has Ewing sarcoma. Approximately 85-90% of Ewing sarcomas harbor the classic t(11;22)(q24;q12) translocation, resulting in the EWSR1-FLI1 fusion protein. The second most common variant, present in about 5-10% of cases, is t(21;22)(q22;q12), which results in the EWSR1-ERG fusion. SYT-SSX is found in synovial sarcoma; ETV6-NTRK3 in infantile fibrosarcoma (and congenital mesoblastic nephroma); PAX3-FOXO1 in alveolar rhabdomyosarcoma; and FUS-DDIT3 in myxoid liposarcoma.

Question 4278

Topic: 10. Pathology and Oncology

A 32-year-old male presents with a slowly enlarging, deep soft tissue mass near the knee joint. He reports intermittent pain for the past 18 months. Radiographs reveal a soft tissue mass with eccentric stippled calcifications. Biopsy demonstrates a biphasic pattern consisting of sheets of uniform spindle cells intertwined with epithelial-like glandular structures. Which cytogenetic abnormality is diagnostic for this tumor?

. t(9;22)(q22;q12)
. t(X;18)(p11;q11)
. t(2;13)(q35;q14)
. t(11;22)(q24;q12)
. t(12;16)(q13;p11)

Correct Answer & Explanation

. t(X;18)(p11;q11)

Explanation

The clinical history, radiographic evidence of calcification (seen in ~30% of cases), and biphasic histology are classic for synovial sarcoma. Synovial sarcoma is uniquely characterized by the balanced reciprocal translocation t(X;18)(p11;q11), leading to the fusion of the SS18 (formerly SYT) gene on chromosome 18 with one of the SSX genes (SSX1, SSX2, or SSX4) on the X chromosome. Despite its name, synovial sarcoma rarely arises directly from the synovium of a joint, but rather from adjacent deep soft tissues.

Question 4279

Topic: 10. Pathology and Oncology
A 40-year-old male with a history of multiple café-au-lait macules and axillary freckling presents with a rapidly enlarging, painful mass in his proximal thigh. He has a known history of a long-standing plexiform neurofibroma at this exact site. Core needle biopsy reveals a high-grade spindle cell sarcoma. Loss of function of which of the following proteins is directly implicated in the pathogenesis of this patient's underlying genetic syndrome and subsequent malignant transformation?
. Merlin, leading to hyperactivation of mTOR
. Neurofibromin, leading to hyperactivation of the RAS pathway
. APC, leading to beta-catenin accumulation
. p53, leading to failure of apoptosis
. RB1, leading to uncontrolled cell cycle progression

Correct Answer & Explanation

. Neurofibromin, leading to hyperactivation of the RAS pathway

Explanation

The patient's clinical signs (café-au-lait macules, axillary freckling, plexiform neurofibroma) indicate Neurofibromatosis type 1 (NF1). Patients with NF1 have up to a 10% lifetime risk of a plexiform neurofibroma undergoing malignant transformation into a Malignant Peripheral Nerve Sheath Tumor (MPNST), as described here. NF1 is caused by a mutation in the NF1 gene, which encodes the protein neurofibromin. Neurofibromin is a GTPase-activating protein (GAP) that negatively regulates the RAS signaling pathway. Loss of neurofibromin leads to unopposed, hyperactive RAS signaling, promoting tumorigenesis.

Question 4280

Topic: 10. Pathology and Oncology

A 45-year-old male presents with bone pain and is found to have multifocal lytic bone lesions in the lower extremity. A biopsy shows cords and nests of epithelioid cells set in a myxohyaline stroma. Many cells contain intracytoplasmic vacuoles that resemble primitive vascular lumens, some containing erythrocytes. The tumor cells are strongly positive for CD31 and ERG. Molecular testing reveals a WWTR1-CAMTA1 gene fusion. Which of the following is the most likely diagnosis?

. Angiosarcoma
. Epithelioid sarcoma
. Epithelioid hemangioendothelioma
. Metastatic renal cell carcinoma
. Adamantinoma

Correct Answer & Explanation

. Epithelioid hemangioendothelioma

Explanation

The clinical, histologic, and molecular findings are diagnostic of Epithelioid Hemangioendothelioma (EHE) of bone. EHE is a rare vascular tumor of intermediate to malignant potential. It frequently presents with multifocal bone involvement. Histologically, it features epithelioid cells with distinctive intracytoplasmic lumina ("blister cells") in a myxohyaline stroma. It expresses endothelial markers like CD31, CD34, and ERG. The hallmark molecular alteration is the t(1;3)(p36;q25) translocation, resulting in the WWTR1-CAMTA1 fusion gene, which is highly specific for EHE and differentiates it from angiosarcoma or epithelioid sarcoma.

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