Immobilization with a sling

Aspiration and steroid injection

A 62-year-old man has cervical myelopathy with no evidence of cervical radiculopathy. MRI reveals stenosis at C4-5 and C5-6 with severe cord compression. Examination will most likely reveal which of the following findings?

Spastic gait and a positive Hoffman’s sign

An otherwise healthy 26-year-old woman is involved in a high speed motor vehicle accident and sustains the injury shown in Figure 54 to her dominant right arm. Appropriate treatment of this injury complex includes

plating of the radius with closed reduction and evaluation of the distal radioulnar joint (DRUJ).

Figures 1 through 4 are the radiographs, sagittal-cut CT scan, and coronal T1 MR image of a 16-year-old boy who has wrist stiffness and pain after sustaining an injury 2 years ago. There is no bleeding from the proximal pole during surgery. Which pro

Free-vascularized medial femoral condyle graft

Orthopedic Tumor MCQ Review & Answers | Dr Hutaif

Question 1

A 15-year-old boy presents with a painful mass in his distal femur. Biopsy confirms osteosarcoma. Which of the following genetic syndromes is most commonly associated with a significantly increased risk of developing this specific malignancy?

Explanation

Li-Fraumeni syndrome is a rare autosomal dominant disorder caused by a germline mutation in the TP53 tumor suppressor gene, predisposing individuals to osteosarcoma, breast cancer, brain tumors, and soft tissue sarcomas. Retinoblastoma (RB1 mutation) is also strongly associated with osteosarcoma development.

Question 2

A 55-year-old male presents with deep, aching thigh pain. Radiographs reveal a lytic lesion in the proximal femur with 'popcorn' calcification and endosteal scalloping greater than two-thirds of the cortical thickness. What is the most appropriate next step in management?

Explanation

The radiographic features (popcorn calcification, deep endosteal scalloping > 2/3 of cortical thickness, accompanied by pain) suggest a high-grade or dedifferentiated chondrosarcoma rather than a benign enchondroma. The appropriate management is biopsy followed by wide surgical resection, as chondrosarcomas are generally resistant to chemotherapy and radiation.

Question 3

A 12-year-old girl is evaluated for a permeative lesion in the diaphysis of the humerus with an associated 'onion-skin' periosteal reaction. A biopsy is performed. Which of the following chromosomal translocations is most characteristic of the suspected diagnosis?

Explanation

The clinical and radiographic presentation is classic for Ewing sarcoma. The characteristic translocation is t(11;22)(q24;q12), which results in the EWS-FLI1 fusion protein. This occurs in approximately 85% of Ewing sarcoma cases.

Question 4

A 32-year-old female complains of knee pain. Radiographs demonstrate an eccentric, lytic, epiphyseal lesion in the proximal tibia extending to the subchondral bone without a sclerotic margin. Histology shows multinucleated giant cells in a stroma of mononuclear cells. Which of the following medical treatments can be used as an adjuvant to surgery or for unresectable disease?

Explanation

The presentation is classic for a Giant Cell Tumor (GCT) of bone. Denosumab, a monoclonal antibody that acts as a RANKL inhibitor, is highly effective in treating GCT by preventing the RANKL-mediated maturation and activation of osteoclast-like giant cells, leading to tumor consolidation.

Question 5

A 19-year-old male presents with progressive back pain that is worse at night and poorly relieved by NSAIDs. Imaging reveals a 2.5 cm radiolucent nidus with surrounding sclerosis in the posterior elements of L4. What is the most likely diagnosis?

Explanation

While osteoid osteoma and osteoblastoma are histologically similar, osteoblastomas are distinguished by a nidus size greater than 2 cm (often >1.5-2 cm) and pain that is less responsive to NSAIDs. They commonly occur in the posterior elements of the spine.

Question 6

A 14-year-old boy has an expansile, multiloculated, eccentrically located lytic lesion in the distal femoral metaphysis. MRI demonstrates multiple fluid-fluid levels. What is the most common underlying genetic abnormality associated with a primary form of this lesion?

Explanation

Primary Aneurysmal Bone Cysts (ABCs) are true neoplastic processes characterized by translocations involving the USP6 gene on chromosome 17p13. Fluid-fluid levels on MRI are characteristic, though not entirely pathognomonic, for ABCs.

Question 7

An asymptomatic 40-year-old female has an incidental finding of a well-circumscribed cartilaginous lesion in the proximal humerus with punctate calcifications. There is no endosteal scalloping or periosteal reaction. Which of the following is the most appropriate management?

Explanation

This is a classic presentation of an asymptomatic enchondroma. Without signs of aggressive behavior (e.g., deep endosteal scalloping >2/3, rest pain, cortical breakthrough), the standard of care is observation with serial imaging.

Question 8

In the staging of soft tissue sarcomas according to the Musculoskeletal Tumor Society (Enneking) staging system, which of the following defines a stage IIB tumor?

Explanation

In the Enneking system for sarcomas: Stage I is low grade, Stage II is high grade, and Stage III indicates metastases. The letter 'A' denotes intracompartmental location, and 'B' denotes extracompartmental. Thus, Stage IIB is a high-grade, extracompartmental lesion.

Question 9

A 28-year-old male presents with a slow-growing mass in his foot. MRI shows a multilobulated mass near the plantar fascia. Biopsy reveals a biphasic tumor with both epithelial and spindle cell components. Which cytogenetic abnormality is diagnostic for this tumor?

Explanation

The tumor described is a synovial sarcoma, which frequently presents in the distal extremities of young adults and is characterized histologically by biphasic or monophasic patterns. The diagnostic translocation is t(X;18)(p11;q11), creating the SYT-SSX fusion gene.

Question 10

A 30-year-old female presents with a painless mass on the posterior aspect of her distal thigh. Radiographs show a dense, heavily ossified mass attached to the posterior cortex of the distal femur with a 'string sign'. What is the most likely diagnosis?

Explanation

Parosteal osteosarcoma is a low-grade surface osteosarcoma that typically occurs on the posterior aspect of the distal femur. It presents as a heavily ossified mass, often with a radiolucent cleft (string sign) separating it from the underlying cortex.

Question 11

A 65-year-old male presents with a destructive lytic lesion in the proximal humerus. Biopsy is planned. Medical history includes a nephrectomy 5 years ago for renal cell carcinoma. What is a critical pre-operative step before performing an intralesional curettage or stabilization?

Explanation

Renal cell carcinoma and thyroid carcinoma metastases to bone are notoriously hypervascular. Pre-operative embolization is highly recommended to significantly reduce intraoperative blood loss during biopsy or surgical stabilization.

Question 12

A 9-year-old boy sustains a minor fall and presents with arm pain. Radiographs reveal a fracture through a centrally located, completely lytic lesion in the proximal humerus metaphysis. A 'fallen leaf' sign is noted. What is the most appropriate initial management for the cyst after the fracture has healed?

Explanation

The lesion is a Unicameral (Simple) Bone Cyst (UBC), indicated by its central location, purely lytic nature, and the pathognomonic 'fallen leaf' (fallen fragment) sign. After fracture healing, treatment options include observation (some resolve spontaneously after fracture) or less invasive interventions like corticosteroid or bone marrow aspirate injections.

Question 13

A 62-year-old man presents with generalized bone pain, fatigue, and renal impairment. Radiographs show multiple 'punched-out' lytic lesions in the skull and pelvis. Which of the following laboratory findings is most specific for confirming the diagnosis?

Explanation

The clinical picture (CRAB criteria: hyperCalcemia, Renal involvement, Anemia, Bone lytic lesions) is classic for Multiple Myeloma. A monoclonal spike (M-protein) on serum or urine protein electrophoresis (SPEP/UPEP) confirms the diagnosis of a plasma cell dyscrasia.

Question 14

A 25-year-old female presents with a painless bowing deformity of her proximal femur. Radiographs reveal a ground-glass intramedullary lesion with cortical thinning and a 'shepherd's crook' deformity. The underlying pathophysiology involves a mutation in which of the following?

Explanation

The presentation is consistent with fibrous dysplasia, characterized by the 'ground-glass' appearance and bowing deformities (shepherd's crook in the proximal femur). The etiology is a somatic activating mutation in the GNAS1 gene, which encodes the alpha subunit of the stimulatory G protein.

Question 15

A 7-year-old boy presents with mid-back pain. Lateral spine radiographs demonstrate vertebra plana (a uniformly flattened vertebral body). The adjacent disc spaces are preserved. Biopsy of the lesion would most likely reveal cells positive for which immunohistochemical markers?

Explanation

Vertebra plana in a child is highly characteristic of Eosinophilic Granuloma (Langerhans Cell Histiocytosis). The Langerhans cells in this condition are characteristically positive for S-100 and CD1a, and contain Birbeck granules on electron microscopy.

Question 16

A 35-year-old male presents with an indolent, progressive swelling over the anterior shin. Radiographs show a multilobular, eccentric, diaphyseal lytic lesion in the anterior cortex of the tibia. Histopathology shows islands of epithelial cells in a fibrous stroma. What is the most appropriate definitive management?

Explanation

The lesion is an adamantinoma, a rare low-grade malignant bone tumor that almost exclusively occurs in the anterior diaphyseal cortex of the tibia. Because it is a low-grade malignancy that is relatively resistant to radiation and chemotherapy, wide surgical resection with negative margins is the required definitive treatment.

Question 17

A 40-year-old male with a history of Neurofibromatosis Type 1 (NF1) notices rapid enlargement and pain in a pre-existing plexiform neurofibroma in his thigh. Which of the following is the most likely diagnosis?

Explanation

Patients with NF1 have a 5-10% lifetime risk of developing a Malignant Peripheral Nerve Sheath Tumor (MPNST). Rapid enlargement, new-onset pain, or neurological deficit in a previously stable plexiform neurofibroma is highly suspicious for malignant transformation to an MPNST.

Question 18

A 14-year-old girl has a hard, painless mass on her proximal medial tibia. Radiographs show a sessile, bony prominence pointing away from the joint line with medullary continuity between the lesion and the native bone. What is the approximate risk of malignant transformation for this solitary lesion?

Explanation

The lesion is a solitary osteochondroma. The risk of malignant transformation (typically to secondary chondrosarcoma) in a solitary osteochondroma is very low, estimated to be less than 1%. In contrast, patients with Multiple Hereditary Exostoses (MHE) have a higher risk (approximately 5-10%).

Question 19

A 45-year-old male presents with a deep, painless mass in his posterior thigh. Biopsy confirms myxoid liposarcoma. This specific soft tissue sarcoma is known for a unique pattern of metastasis compared to other soft tissue sarcomas. Where is it most likely to metastasize besides the lungs?

Explanation

While most soft tissue sarcomas metastasize primarily to the lungs, myxoid liposarcoma has a unique propensity to metastasize to extrapulmonary sites, particularly the spine (bone) and other soft tissue locations. A whole-spine MRI is often part of the staging process.

Question 20

A 30-year-old female complains of recurrent knee effusions and mechanical catching. Aspiration yields dark, blood-tinged synovial fluid. MRI reveals a nodular synovial mass with low signal intensity on both T1 and T2 weighted images, exhibiting blooming artifact on gradient-echo sequences. What is the pathological hallmark causing these MRI findings?

Explanation

The clinical and MRI findings are classic for Pigmented Villonodular Synovitis (PVNS), also known as Tenosynovial Giant Cell Tumor. The low signal on T1/T2 and blooming artifact on gradient-echo MRI are caused by extensive hemosiderin deposition within the synovial proliferating tissue.

Question 21

A 45-year-old male presents with a deep soft tissue mass in the anterior thigh. A core needle biopsy is planned. Which of the following principles is strictly recommended during the biopsy of a suspected soft tissue sarcoma?

Explanation

In orthopedic oncology, biopsies must be carefully planned. Longitudinal incisions are mandatory so the tract can be excised en bloc with the tumor during definitive surgery. Strict hemostasis prevents hematoma spread of tumor cells. If a tourniquet is used, the limb should be elevated, NOT exsanguinated with an Esmarch bandage, to avoid pushing tumor cells systemically. Drains should exit in line with the incision, close to it, to allow block excision. Tracts must not contaminate new compartments.

Question 22

A 28-year-old female presents with a painless mass behind her knee. Radiographs reveal a dense, heavily ossified mass attached to the posterior cortex of the distal femur by a broad base, with no medullary involvement. Which of the following molecular abnormalities is most characteristic of this lesion?

Explanation

The clinical and radiographic presentation is classic for parosteal osteosarcoma, a low-grade surface osteosarcoma typically found on the posterior distal femur. The hallmark molecular finding is the amplification of MDM2 and CDK4 on chromosome 12q13-15. t(11;22) is Ewing sarcoma; H3F3A is giant cell tumor; GNAS is fibrous dysplasia; t(X;18) is synovial sarcoma.

Question 23

A 14-year-old boy presents with a painful, swollen mid-thigh mass. Radiographs show a permeative diaphyseal lytic lesion with an 'onion-skin' periosteal reaction. Biopsy reveals sheets of small round blue cells that stain positive for CD99. The most common translocation associated with this tumor results in a fusion protein that functions as a:

Explanation

Ewing sarcoma is characterized by the t(11;22)(q24;q12) translocation in 85% of cases, fusing the EWS gene to the FLI1 gene. The resultant EWS-FLI1 fusion protein acts as an aberrant transcription factor, leading to unregulated cell growth and proliferation.

Question 24

A 30-year-old female presents with an expansile, eccentric lytic lesion in the proximal tibia extending to the subchondral bone. Biopsy confirms Giant Cell Tumor of Bone. She is started on denosumab. What is the primary mechanism of action of this drug?

Explanation

Denosumab is a fully human monoclonal antibody that specifically binds to RANKL (Receptor Activator of Nuclear factor Kappa-B Ligand). By binding to RANKL, it prevents RANKL from binding to the RANK receptor on the surface of osteoclasts and their precursors, thereby inhibiting osteoclast formation, function, and survival. It does not bind to the RANK receptor itself. Bisphosphonates inhibit farnesyl pyrophosphate synthase.

Question 25

A 62-year-old male with a known long-standing asymptomatic calcified lesion in the proximal femur develops sudden, severe thigh pain. Radiographs demonstrate central punctate calcifications with a new, large, adjacent aggressive radiolucent area destroying the cortex. Which of the following is the most accurate statement regarding this condition?

Explanation

This is a classic presentation of dedifferentiated chondrosarcoma, where a low-grade cartilaginous tumor abruptly changes into a high-grade, non-cartilaginous sarcoma (such as osteosarcoma, fibrosarcoma, or undifferentiated pleomorphic sarcoma). It has a very poor prognosis. Treatment requires wide surgical resection, often combined with systemic chemotherapy tailored to the high-grade dedifferentiated component, similar to the treatment of high-grade osteosarcoma.

Question 26

A 48-year-old male presents with progressive proximal muscle weakness, diffuse bone pain, and multiple bilateral insufficiency fractures of the femoral necks and pubic rami. Laboratory tests show significant hypophosphatemia, elevated alkaline phosphatase, normal serum calcium, normal PTH, normal 25-OH vitamin D, and elevated FGF23 levels. Which of the following is the most likely underlying etiology?

Explanation

The patient's presentation is classic for tumor-induced osteomalacia (TIO), a paraneoplastic syndrome caused by a small, slow-growing, benign tumor (typically a phosphaturic mesenchymal tumor) that secretes Fibroblast Growth Factor 23 (FGF23). FGF23 causes renal phosphate wasting and decreases 1,25-dihydroxyvitamin D production, leading to hypophosphatemia, osteomalacia, and insufficiency fractures. Resection of the tumor is curative.

Question 27

A 28-year-old female presents with a slow-growing, deep, painful mass near her ankle joint. Radiographs reveal a soft tissue mass with stippled calcifications. Biopsy demonstrates a biphasic pattern of epithelial and spindle cells. Which genetic translocation is diagnostic for this tumor?

Explanation

Synovial sarcoma classically presents in young adults as a deep-seated mass in the extremities, often near a joint, and frequently exhibits calcifications on radiographs. The diagnostic translocation is t(X;18)(p11;q11), leading to the SYT-SSX (or SS18-SSX) fusion gene. t(11;22) is Ewing sarcoma, t(12;16) is myxoid liposarcoma, t(9;22) is extraskeletal myxoid chondrosarcoma, and t(2;13) is alveolar rhabdomyosarcoma.

Question 28

A 35-year-old male presents with a painless, eccentric, expansile 'soap-bubble' lytic lesion in the anterior diaphyseal cortex of the tibia. A biopsy reveals islands of epithelial cells within a benign-appearing fibrous stroma. What is the most appropriate surgical management for this patient?

Explanation

The diagnosis is adamantinoma, a rare, low-grade malignant bone tumor that almost exclusively occurs in the anterior diaphyseal cortex of the tibia. Histologically, it is biphasic with epithelial cells in a fibrous stroma. Because it is a low-grade malignancy with a high rate of local recurrence and potential for metastasis, the standard of care is wide en bloc resection. Curettage results in unacceptably high recurrence rates.

Question 29

A 16-year-old boy presents with knee pain. Radiographs demonstrate an eccentric, expansile, purely lytic lesion in the distal femur metaphysis. MRI shows multiple fluid-fluid levels. Genetic analysis of the tissue is most likely to show a rearrangement involving which of the following genes?

Explanation

The lesion described is an aneurysmal bone cyst (ABC), characterized by eccentric, expansile lytic lesions with fluid-fluid levels on MRI. Primary ABCs are now known to be true neoplasms, characterized by a recurrent t(16;17) translocation that results in the upregulation of the USP6 gene (ubiquitin-specific protease 6). GNAS is seen in fibrous dysplasia, H3F3A in giant cell tumor, EXT1 in multiple hereditary exostoses, and MDM2 in parosteal osteosarcoma.

Question 30

A 55-year-old female with a history of breast cancer presents with right thigh pain. Radiographs show a lytic metastatic lesion in the peritrochanteric region of the femur. The lesion involves approximately 50% of the cortical diameter. She describes her pain as moderate with weight-bearing. Using Mirels' criteria, what is her score and recommended management?

Explanation

Mirels' criteria assess the risk of pathologic fracture. Variables are scored 1-3: Site (Upper limb=1, Lower limb=2, Peritrochanteric=3), Size (<1/3=1, 1/3-2/3=2, >2/3=3), Nature (Blastic=1, Mixed=2, Lytic=3), Pain (Mild=1, Moderate=2, Functional=3). Score: Peritrochanteric (3) + 50% diameter (2) + Lytic (3) + Moderate pain (2) = 10. A score of 9 or greater carries a high fracture risk, and prophylactic fixation is recommended.

Question 31

A 32-year-old male with a history of total colectomy for familial adenomatous polyposis (FAP) presents with a deep, firm mass in his posterior thigh. Biopsy shows a proliferation of uniform spindle cells in a dense collagenous background, with absent mitotic activity. Which of the following proteins is most likely to show aberrant nuclear accumulation on immunohistochemistry?

Explanation

The patient has a deep fibromatosis (desmoid tumor), strongly associated with Gardner syndrome (caused by APC gene mutations). Both sporadic and syndromic desmoid tumors result in the dysregulation of the Wnt/beta-catenin signaling pathway. The hallmark immunohistochemical finding is aberrant nuclear accumulation of beta-catenin.

Question 32

A 68-year-old male presents with generalized bone pain, anemia, hypercalcemia, and renal dysfunction. Skeletal survey reveals multiple 'punched-out' lytic lesions in the skull and pelvis. The severe osteolytic bone destruction seen in this condition is primarily mediated by myeloma cell-induced:

Explanation

Multiple myeloma causes lytic bone lesions via uncoupling of normal bone remodeling. Myeloma cells interact with bone marrow stromal cells to upregulate RANKL and downregulate OPG (a decoy receptor for RANKL). This severely increased RANKL/OPG ratio leads to massive osteoclast activation and bone resorption.

Question 33

A 55-year-old male presents with chronic constipation, urinary hesitancy, and vague sacral pain. MRI shows a large, destructive, midline lobulated mass in the sacrum. Biopsy reveals large cells with prominent intracytoplasmic vacuoles arranged in cords. Which immunohistochemical marker is highly specific for the diagnosis of this tumor?

Explanation

The clinical and histologic description is classic for chordoma, a slow-growing malignant tumor arising from notochord remnants. Histologically, it features 'physaliferous' cells (large cells with bubbly, vacuolated cytoplasm). Brachyury, a transcription factor essential for notochord development, is highly specific for chordoma.

Question 34

A 40-year-old male presents with shoulder pain. Radiographs demonstrate an expansile, radiolucent lesion in the epiphysis of the proximal humerus with focal calcifications. A biopsy is read as showing 'chondroblastic cells, multinucleated giant cells, and areas of hyaline cartilage.' Given the patient's age and location, what is the most likely diagnosis, and what is the required treatment?

Explanation

While chondroblastoma presents as an epiphyseal lytic lesion with giant cells and chondroblasts, it typically occurs in skeletally immature patients (teens). In an adult (e.g., 40-year-old) with a similar epiphyseal lesion, clear cell chondrosarcoma must be strongly suspected. It is a low-grade malignancy that requires wide en bloc resection to prevent local recurrence and metastasis.

Question 35

A 58-year-old female presents with a rapidly growing, painful mass in her left scapula. She underwent a lumpectomy and local radiation therapy for left breast cancer 15 years ago. Biopsy of the scapular mass reveals a high-grade, pleomorphic spindle cell sarcoma producing osteoid. According to Cahan's criteria for radiation-induced sarcoma, all of the following must be met EXCEPT:

Explanation

Cahan's criteria define a radiation-induced sarcoma: 1) The sarcoma must arise in the area previously irradiated; 2) The patient must have had a latency period, which is typically greater than 3-5 years (but not strictly 15 years); 3) Histologic proof of the sarcoma; 4) The sarcoma must be histologically distinct from the primary tumor. Osteosarcoma and UPS are the most common radiation-induced sarcomas.

Question 36

An 18-year-old male presents with a painful swelling over the anterior tibia. Radiographs show a radiolucent surface lesion in the diaphysis with crater-like scalloping of the underlying cortex and perpendicular bone spicules ('hair-on-end'). MRI confirms no medullary involvement. Histology shows predominantly intermediate-grade chondroblastic matrix. What is the diagnosis?

Explanation

Periosteal osteosarcoma is a rare, intermediate-grade surface osteosarcoma that typically arises on the diaphysis of long bones. Radiographically, it causes a scalloped saucerization of the outer cortex with perpendicular spicules of bone. Histologically, it is predominantly chondroblastic. Parosteal osteosarcoma is low-grade, heavily ossified, fibroblastic, and typically posterior distal femur.

Question 37

A 7-year-old boy presents with mid-back pain. Lateral spine radiographs demonstrate complete collapse of the T8 vertebral body (vertebra plana) with preserved adjacent disc spaces. Biopsy of the lesion reveals a proliferation of mononuclear cells with folded, 'coffee-bean' nuclei and eosinophils. Electron microscopy would classically reveal which of the following structures?

Explanation

The presentation of vertebra plana in a child, combined with the characteristic histology, points to Langerhans Cell Histiocytosis (eosinophilic granuloma). The hallmark finding on electron microscopy for LCH is the presence of Birbeck granules, which have a characteristic 'tennis racket' appearance.

Question 38

A 24-year-old male presents with a 6-month history of a dull, aching back pain that is not completely relieved by NSAIDs. CT scan reveals a 3.5 cm expansile, lytic lesion with scattered central calcifications in the posterior elements of L4. Biopsy shows prominent osteoblastic rimming of osteoid trabeculae within a highly vascular connective tissue stroma. What is the most common secondary change or complication associated with this lesion?

Explanation

The lesion described is an osteoblastoma (>2 cm, posterior elements of spine, histologically identical to osteoid osteoma but larger and less responsive to NSAIDs). Osteoblastomas have a high tendency to undergo secondary changes, most notably the development of a secondary aneurysmal bone cyst (ABC) in up to 10-15% of cases.

Question 39

A 45-year-old female undergoes a wide resection of a 7 cm deep soft tissue mass in the vastus medialis. Pathology confirms a high-grade undifferentiated pleomorphic sarcoma. MRI and intraoperative findings confirm the tumor was strictly confined within the deep fascia of the anterior compartment of the thigh, without bony or neurovascular involvement. A staging PET-CT shows no regional or distant metastases. What is the Enneking Surgical Stage for this patient?

Explanation

The Enneking staging system relies on Grade (G1=Low, G2=High), Site (T1=Intracompartmental, T2=Extracompartmental), and Metastasis (M0=None, M1=Mets). This tumor is high-grade (G2), which places it in Stage II. It is confined within the compartment (T1), making it IIA. There are no metastases (M0).

Question 40

A 42-year-old male is diagnosed with a large, deep myxoid liposarcoma of the posterior thigh. Genetic testing confirms the characteristic t(12;16) FUS-DDIT3 translocation. During the staging workup, the oncologist recommends a whole-body MRI rather than relying solely on a chest CT. This recommendation is based on the unique propensity of myxoid liposarcoma to metastasize to which of the following locations?

Explanation

Myxoid liposarcoma has a unique metastatic pattern. While most soft tissue sarcomas metastasize primarily to the lungs, myxoid liposarcoma frequently metastasizes to extrapulmonary sites, particularly other soft tissues, the retroperitoneum, and bone/spine, often before pulmonary involvement. Therefore, whole-body MRI or spine MRI is required for staging.

Question 41

A 25-year-old male presents with a slow-growing, deep-seated soft tissue mass around the knee. Radiographs reveal focal stippled calcifications within the soft tissue mass. Core needle biopsy demonstrates a biphasic tumor consisting of both epithelial elements arranged in glandular structures and a spindle cell component. What is the defining chromosomal translocation associated with this malignancy?

Explanation

The clinical and histological presentation describes a synovial sarcoma, which frequently presents near joints in young adults and often contains focal calcifications (in about 30% of cases). The classic genetic hallmark is the t(X;18)(p11;q11) translocation, resulting in the SYT-SSX fusion gene. t(11;22) is seen in Ewing sarcoma; t(12;16) in myxoid liposarcoma; t(2;13) in alveolar rhabdomyosarcoma; and t(9;22) in extraskeletal myxoid chondrosarcoma (and CML).

Question 42

A 60-year-old female with a history of breast cancer presents with a mixed lytic and blastic lesion in the peritrochanteric region of the right femur. The lesion involves 2/3 of the cortical diameter. She reports moderate pain with ambulation. According to Mirels' criteria, what is the patient's calculated score and the most appropriate orthopedic management?

Explanation

Mirels' criteria are used to determine the risk of impending pathologic fracture. The criteria assess four categories (Site, Pain, Lesion type, Size) with points from 1 to 3. Site: Peritrochanteric (lower limb) = 2. Pain: Moderate = 2. Lesion: Mixed = 2. Size: 2/3 (>1/3 to 2/3) = 3. Total score = 2 + 2 + 2 + 3 = 9. A score of 9 or greater carries a high risk of fracture (>=33%) and is an indication for prophylactic internal fixation.

Question 43

The Spinal Instability Neoplastic Score (SINS) is used to evaluate the need for surgical stabilization in patients with metastatic spine disease. Which of the following components of the SINS criteria carries the highest maximum point value?

Explanation

The SINS criteria assess six domains. The maximum point values are: Location (3), Pain (3), Bone lesion quality (2), Radiographic spinal alignment (4), Vertebral body collapse (3), and Posterolateral involvement (3). Radiographic spinal alignment carries the highest possible score (4 points for subluxation/translation).

Question 44

A 65-year-old male is scheduled for a wide resection and intercalary reconstruction of a destructive lytic lesion in the humeral diaphysis. His medical history is significant for a prior nephrectomy for renal cell carcinoma. Which preoperative intervention is most critical to minimize intraoperative morbidity?

Explanation

Metastatic lesions from renal cell carcinoma (RCC) and thyroid carcinoma are notoriously hypervascular. Preoperative selective angiography and embolization performed 24-48 hours before surgery are critical to minimize catastrophic intraoperative blood loss. Neoadjuvant radiation or chemotherapy are not standard immediate preoperative modalities for metastatic RCC in this context.

Question 45

A 45-year-old female presents with a destructive bone lesion in her left scapula. Fifteen years ago, she underwent lumpectomy and adjuvant radiation therapy for breast cancer. Biopsy of the scapular lesion reveals high-grade pleomorphic spindle cells producing osteoid. According to Cahan's criteria, which of the following is essential to establish a diagnosis of radiation-induced sarcoma?

Explanation

Cahan's criteria for radiation-induced sarcoma include: 1) The sarcoma must arise within the previously irradiated field; 2) A latent period must exist (typically >4 years, average 10-15 years); 3) The histology must be distinct from the primary tumor; 4) There must be histological proof of a sarcoma. Therefore, the tumor arising strictly within the prior radiation field is an essential criterion.

Question 46

A 14-year-old boy presents with chronic knee pain. Radiographs demonstrate a well-demarcated, lytic lesion in the distal femoral epiphysis with a sclerotic margin. Histological examination of the curettage specimen is most likely to reveal which of the following?

Explanation

The clinical and radiographic presentation describes a chondroblastoma (an epiphyseal lytic lesion in an open physis). The classic histological findings are mononuclear cells (chondroblasts), scattered osteoclast-like multinucleated giant cells, and distinctive fine, lacy, 'chicken-wire' pericellular calcification. Fibrous dysplasia (woven bone lacking osteoblastic rimming) is diaphyseal/metaphyseal.

Question 47

A 40-year-old male presents with a painless, deep intramuscular mass in the posterior thigh. MRI reveals a lesion with intermediate signal on T1 and marked hyperintensity on T2. Biopsy demonstrates a prominent plexiform capillary network and lipoblasts within a myxoid stroma. What is the expected chromosomal translocation for this tumor?

Explanation

The diagnosis is myxoid liposarcoma, characterized histologically by a myxoid background, 'crow's feet' or plexiform capillary network, and lipoblasts. The characteristic genetic alteration is the t(12;16)(q13;p11) translocation, resulting in the FUS-DDIT3 (or FUS-CHOP) fusion transcript. These tumors are uniquely sensitive to radiation therapy.

Question 48

A 5-year-old boy presents with anterior bowing of the tibia. Radiographs show an eccentric, multi-loculated lytic lesion in the anterior cortex of the tibial diaphysis. Biopsy reveals a fibrous stroma containing trabeculae of woven bone with prominent osteoblastic rimming. Immunohistochemical staining for cytokeratin is negative. What is the most appropriate initial management?

Explanation

The clinical, radiographic, and histological picture describes osteofibrous dysplasia (Campanacci disease). It occurs almost exclusively in the anterior tibia in young children (unlike fibrous dysplasia, the woven bone here HAS prominent osteoblastic rimming, and cytokeratin is negative, ruling out adamantinoma). Management is primarily observation and bracing (watchful waiting) because the lesion often stabilizes or regresses after skeletal maturity, and early surgery carries a high risk of recurrence.

Question 49

A 55-year-old female presents with diffuse bone pain. Radiographs reveal multiple expansile, lytic lesions in the pelvis and bilateral femurs. Biopsy of a pelvic lesion demonstrates clusters of multinucleated giant cells embedded in a highly vascularized, hemorrhagic fibrous stroma. Routine laboratory workup reveals significantly elevated serum calcium and alkaline phosphatase. Which additional test is most likely to confirm the underlying etiology?

Explanation

The presence of multiple lytic lesions with histology showing multinucleated giant cells in a hemorrhagic stroma ('brown tumor'), accompanied by hypercalcemia and elevated alkaline phosphatase, strongly suggests hyperparathyroidism. Confirming the etiology requires checking the intact parathyroid hormone (PTH) level. Brown tumors are not true neoplasms but rather a reactive cellular process due to intense osteoclastic bone resorption.

Question 50

An 18-year-old male is undergoing treatment with the MAP protocol (High-dose Methotrexate, Adriamycin/Doxorubicin, and Cisplatin) for high-grade conventional osteosarcoma of the distal femur. Six months into treatment, he presents with progressive dyspnea on exertion, orthopnea, and lower extremity edema. Echocardiography reveals a significantly reduced left ventricular ejection fraction. Which chemotherapeutic agent is most likely responsible?

Explanation

Doxorubicin (Adriamycin) is an anthracycline known for causing dose-dependent, cumulative, and potentially irreversible cardiotoxicity (cardiomyopathy leading to congestive heart failure). Cisplatin is associated with ototoxicity and nephrotoxicity. Methotrexate is associated with hepatotoxicity, mucositis, and myelosuppression. Ifosfamide is known for hemorrhagic cystitis. Bleomycin is associated with pulmonary fibrosis.

Question 51

A 22-year-old male presents with mild proximal tibial pain. Radiographs show an eccentric, lytic metaphyseal lesion with a well-defined sclerotic margin, lacking internal calcification. Histology reveals a lobulated pattern of myxoid and chondroid tissue. The cells are stellate, and there is distinctly increased cellularity at the periphery of the lobules. What is the most likely diagnosis?

Explanation

Chondromyxoid fibroma (CMF) is a rare benign cartilage tumor typically presenting as an eccentric metaphyseal lesion with a sclerotic rim. Classic histology demonstrates a lobular architecture with myxoid/chondroid stroma and increased cellularity at the lobule peripheries (often with osteoclast-like giant cells). Unlike enchondromas or chondroblastomas, it rarely exhibits internal calcification on imaging.

Question 52

A 12-year-old boy presents with multiple bony prominences around his knees and wrists, associated with bowing of the forearms. Genetic testing reveals a mutation in the EXT1 gene. This mutation primarily disrupts the synthesis of which of the following extracellular matrix components?

Explanation

The patient has Multiple Hereditary Exostoses (MHE) or osteochondromatosis. It is inherited in an autosomal dominant pattern and caused by mutations in the EXT1 or EXT2 genes. These genes encode glycosyltransferases essential for the biosynthesis of heparan sulfate. The resulting deficiency in heparan sulfate proteoglycans disrupts normal Indian hedgehog (Ihh) signaling at the growth plate, leading to osteochondroma formation.

Question 53

A resident is performing an open incisional biopsy of a suspected high-grade soft tissue sarcoma located in the vastus lateralis muscle of the thigh. Which of the following technical principles is mandatory to prevent compromising future definitive limb-salvage surgery?

Explanation

During biopsy of a suspected sarcoma, strict compartmentalization rules apply. Meticulous hemostasis is mandatory to prevent a hematoma from tracking tumor cells into adjacent pristine compartments. Incisions must be longitudinal (so the tract can be excised en bloc). Flaps should not be raised. Neurovascular bundles must not be unnecessarily exposed (risks contamination). The viable periphery, not the necrotic center, should be biopsied.

Question 54

A 16-year-old female presents with a rapidly enlarging, painful mass in her distal femur. Imaging shows an expansile, eccentric metaphyseal lytic lesion. MRI reveals multiple fluid-fluid levels. Biopsy shows blood-filled cavernous spaces lacking an endothelial lining, surrounded by spindle cells and multinucleated giant cells. Recent molecular studies demonstrate that the primary form of this lesion is frequently driven by a genetic translocation involving which gene?

Explanation

The lesion is an Aneurysmal Bone Cyst (ABC). Primary ABCs are now known to be true neoplasms driven by specific translocations, most commonly t(16;17), which results in the upregulation of the USP6 gene (ubiquitin-specific protease 6). Secondary ABCs (arising in GCT, chondroblastoma, etc.) lack this USP6 translocation.

Question 55

A 35-year-old male presents with a slow-growing, indolent 'bubbly' lytic lesion in the anterior diaphysis of the tibia. Biopsy reveals a biphasic tumor consisting of nests of epithelial cells within a benign-appearing fibrous stroma. Immunohistochemistry is strongly positive for cytokeratin. Due to its biological behavior, what is the standard surgical treatment for this primary lesion?

Explanation

The diagnosis is Adamantinoma, a low-grade malignant bone tumor predominantly occurring in the anterior tibial diaphysis. Histology shows a biphasic pattern (epithelial and fibrous elements), and the epithelial cells are cytokeratin positive. Because it is a malignant tumor with the potential to metastasize (most commonly to the lungs), the standard of care is wide en bloc resection, usually followed by intercalary reconstruction. Curettage leads to unacceptable recurrence rates.

Question 56

A 45-year-old female with known polyostotic fibrous dysplasia presents with a newly noticed, painless soft tissue mass in her right anterior thigh. MRI shows a well-circumscribed, T2-hyperintense intramuscular lesion. Biopsy reveals hypocellular, abundant myxoid stroma with rare bland spindle cells and no lipoblasts. The combination of these findings characterizes which of the following syndromes?

Explanation

Mazabraud syndrome is the rare association of single or multiple intramuscular myxomas (the soft tissue mass described) with fibrous dysplasia (which may be monostotic or polyostotic). McCune-Albright syndrome features fibrous dysplasia, precocious puberty, and cafe-au-lait spots. Maffucci syndrome involves multiple enchondromas and soft tissue hemangiomas.

Question 57

Zoledronic acid is frequently administered to patients with metastatic bone disease to reduce the incidence of skeletal-related events (SREs). What is the primary intracellular mechanism of action of this medication in inhibiting osteoclast function?

Explanation

Nitrogen-containing bisphosphonates (such as zoledronic acid and alendronate) are internalized by osteoclasts and act by inhibiting farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway. This prevents the prenylation of small GTPase proteins essential for osteoclast survival and cytoskeletal function, leading to osteoclast apoptosis. Denosumab binds RANKL. Cathepsin K inhibitors (like odanacatib) directly inhibit the enzyme.

Question 58

A 28-year-old female is evaluated for a new onset seizure. Workup reveals a solitary brain metastasis. Thorough systemic staging uncovers a slow-growing, highly vascular soft tissue mass deep in her right thigh. Biopsy of the thigh mass reveals large, uniform, polygonal cells arranged in discrete nests separated by delicate sinusoidal vascular channels. A genetic translocation resulting in an ASPSCR1-TFE3 fusion is detected. Which sarcoma is this?

Explanation

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma typically affecting young adults. It is notorious for early hematogenous metastasis, particularly to the brain and lungs, often before the primary tumor is detected. Histologically, it features large polygonal cells in a pseudoalveolar (nesting) pattern. It is characterized by the t(X;17)(p11;q25) translocation, yielding the ASPSCR1-TFE3 fusion.

Question 59

A 30-year-old female presents with a firm mass on the posterior aspect of her distal thigh. Radiographs demonstrate a dense, heavily ossified mass arising from the surface of the posterior distal femur. There is a broad base of attachment to the cortex, and cross-sectional imaging confirms no medullary continuity. Histology shows low-grade, well-differentiated bone and fibrous tissue. Which of the following molecular alterations is classically associated with this specific tumor?

Explanation

The clinical and radiographic presentation describes a parosteal osteosarcoma (surface osteosarcoma, typically low-grade, arising posterior distal femur, lacking medullary continuity unlike an osteochondroma). Parosteal osteosarcomas, like atypical lipomatous tumors/well-differentiated liposarcomas, are characterized by supernumerary ring chromosomes containing amplifications of the 12q13-15 region, which includes the MDM2 and CDK4 genes. EXT1 is for osteochondromas, GNAS for fibrous dysplasia, USP6 for ABC, H3F3A for giant cell tumor of bone.

Question 60

A patient with Ewing sarcoma undergoes systemic staging. Which of the following represents the most significant adverse prognostic factor for overall survival in this patient?

Explanation

While large tumor volume (>200 mL), pelvic location, and poor response to chemotherapy are all well-established poor prognostic factors in Ewing sarcoma, the single most significant adverse prognostic factor is the presence of distant metastases at presentation, specifically bone or bone marrow metastases (which carry a worse prognosis than isolated pulmonary metastases). Overall survival drops to <30% in these patients.

Question 61

A 28-year-old male presents with a slowly enlarging, painless mass near his knee joint. Radiographs reveal a soft tissue mass with stippled calcifications. Biopsy demonstrates a biphasic tumor with both epithelial and spindle cell components. Which of the following genetic translocations is most characteristic of this lesion?

Explanation

Synovial sarcoma is characterized by the t(X;18)(p11;q11) translocation, resulting in the SYT-SSX fusion gene. It commonly presents in young adults near joints (though rarely intra-articular) and shows stippled calcifications on radiographs in about 30% of cases.

Question 62

A 40-year-old male presents with shoulder pain. Radiographs show a lytic lesion in the proximal humeral epiphysis with central calcifications. Histological examination reveals tumor cells with abundant clear cytoplasm, distinct cell membranes, and scattered areas of conventional chondrosarcoma. What is the most likely diagnosis?

Explanation

Clear cell chondrosarcoma typically occurs in the epiphysis of long bones in adults (often older than those with chondroblastoma, which is also epiphyseal). Histology shows sheets of clear cells and may have areas of conventional low-grade chondrosarcoma.

Question 63

A 65-year-old female presents with a new onset of severe thigh pain. Radiographs show a longstanding calcified lesion in the medullary canal of the femur with a new, aggressive, lytic area destroying the cortex. Biopsy reveals a bimorphic pattern with a low-grade cartilaginous tumor abruptly transitioning to a high-grade spindle cell sarcoma. Which of the following best describes the prognosis and treatment?

Explanation

Dedifferentiated chondrosarcoma features a low-grade cartilaginous tumor abruptly transitioning into a high-grade non-cartilaginous sarcoma. It is highly aggressive with a very poor prognosis. Treatment typically involves wide surgical resection and chemotherapy (similar to osteosarcoma protocols), though long-term survival remains low.

Question 64

Which of the following soft tissue sarcomas is most strongly associated with the t(2;13)(q35;q14) translocation, resulting in the PAX3-FOXO1 fusion protein, and often presents in the deep soft tissues of the extremities in adolescents?

Explanation

Alveolar rhabdomyosarcoma typically presents in adolescents and young adults, often in the extremities, and is driven by the t(2;13) or t(1;13) translocation involving PAX3 or PAX7 and FOXO1. Embryonal RMS is more common in younger children and lacks this specific translocation.

Question 65

A 35-year-old male presents with an indolent swelling over the anterior aspect of his middle tibia. Imaging reveals a multilocular, diaphyseal eccentric osteolytic lesion with a 'soap-bubble' appearance. Immunohistochemistry of the biopsy specimen is strongly positive for cytokeratins. What is the most appropriate definitive management?

Explanation

Adamantinoma is a rare, low-grade malignant bone tumor predominantly found in the anterior tibial diaphysis. It features an epithelial component (cytokeratin positive). Due to its risk of local recurrence and potential for metastasis, the treatment of choice is wide surgical resection. It does not respond well to chemotherapy or radiation.

Question 66

Epithelioid hemangioendothelioma (EHE) of bone is a rare vascular tumor. Which of the following statements regarding the behavior and presentation of EHE in bone is most accurate?

Explanation

Vascular tumors of bone, including epithelioid hemangioendothelioma and hemangioma, uniquely have a tendency to be multifocal within the same anatomic region or a single limb (regional multicentricity). EHE is driven by a WWTR1-CAMTA1 fusion, not EWSR1-FLI1.

Question 67

In a patient diagnosed with multiple myeloma, which of the following laboratory markers is considered the most powerful independent prognostic indicator of survival and is incorporated into the International Staging System (ISS)?

Explanation

Serum beta-2 microglobulin (along with serum albumin) forms the basis of the International Staging System (ISS) for multiple myeloma and is the most significant prognostic factor. Higher levels correlate with higher tumor burden and a poorer prognosis.

Question 68

A 62-year-old female presents with a destructive lytic lesion in the proximal femur with an impending pathologic fracture. Biopsy confirms metastatic disease. Preoperative angiography and embolization are highly recommended prior to prophylactic stabilization for metastases originating from which of the following primary sources?

Explanation

Metastases from renal cell carcinoma and thyroid carcinoma are notoriously hypervascular. Preoperative selective arterial embolization is strongly recommended to reduce intraoperative blood loss during surgical stabilization or resection.

Question 69

According to Cahan's criteria for the diagnosis of a post-radiation sarcoma, which of the following conditions must be met?

Explanation

Cahan's criteria for post-radiation sarcoma include: 1) The new tumor must arise within the boundaries of the previous radiation field. 2) A latent period must exist (typically >4-5 years). 3) The new tumor must be histologically distinct from the original treated lesion. 4) There must be histological confirmation of the new sarcoma.

Question 70

Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumor (TGCT), is driven by an overexpression of which of the following factors, providing a target for specific medical therapies such as pexidartinib?

Explanation

PVNS/TGCT is characterized by a specific chromosomal translocation t(1;2) that results in the overexpression of Colony-Stimulating Factor 1 (CSF1). This attracts macrophages that form the bulk of the tumor mass. Pexidartinib is a CSF1 receptor inhibitor approved for advanced or inoperable cases.

Question 71

A 25-year-old female presents with an expansile, purely lytic lesion in the mandible. Biopsy reveals spindle cells producing abundant collagen without nuclear atypia, mitosis, or necrosis. The lesion is considered the bony counterpart to aggressive fibromatosis (desmoid tumor). Which genetic pathway is most commonly implicated in the pathogenesis of this tumor?

Explanation

Desmoplastic fibroma is the rare osseous counterpart of soft tissue aggressive fibromatosis (desmoid tumors). These tumors are frequently driven by mutations in the Wnt/beta-catenin pathway (e.g., CTNNB1 or APC mutations), leading to nuclear accumulation of beta-catenin.

Question 72

A 9-year-old boy is scheduled to undergo a Van Nes rotationplasty for an osteosarcoma of the distal femur. For this procedure to be mechanically successful and functional, which of the following anatomical structures must be preserved and fully functional?

Explanation

In a Van Nes rotationplasty, the limb is shortened, rotated 180 degrees, and reattached so that the ankle joint functions as a knee joint. The sciatic nerve MUST be preserved to maintain motor and sensory function to the rotated leg and foot, which will now act as the calf and knee. The femoral vessels are often resected and anastomosed.

Question 73

According to the Enneking surgical margin classification system for musculoskeletal tumors, which of the following best defines a 'radical' margin?

Explanation

In the Enneking system: Intralesional = through tumor; Marginal = through reactive zone/pseudocapsule; Wide = through normal tissue but within the involved compartment; Radical = removal of the entire anatomical compartment containing the tumor, extending from origin to insertion of the involved muscles/bones.

Question 74

A 16-year-old male is receiving neoadjuvant chemotherapy for osteosarcoma using the standard MAP regimen (Methotrexate, Doxorubicin, Cisplatin). He subsequently develops irreversible congestive heart failure. Which of the chemotherapeutic agents is most likely responsible for this specific toxicity?

Explanation

Doxorubicin (Adriamycin) is an anthracycline known for its dose-dependent, cumulative, and potentially irreversible cardiotoxicity (dilated cardiomyopathy and congestive heart failure). Cisplatin is associated with ototoxicity and nephrotoxicity. Methotrexate is associated with mucositis, hepatotoxicity, and renal toxicity.

Question 75

A 55-year-old male presents with chronic back pain and bowel/bladder dysfunction. Imaging reveals a destructive, midline lesion centered in the sacrum. Biopsy demonstrates lobules of large cells with abundant vacuolated cytoplasm (physaliferous cells) set in a myxoid background. The tumor cells are most likely to show strong immunohistochemical positivity for which of the following markers?

Explanation

The clinical picture and histology (physaliferous cells) describe a chordoma, which arises from notochord remnants. Brachyury is a transcription factor critical for notochord development and is a highly sensitive and specific immunohistochemical marker for chordoma.

Question 76

A 20-year-old female presents with mild chronic leg pain. Radiographs show an eccentric, lytic, expansile lesion in the proximal tibial metaphysis with a well-defined, scalloped sclerotic margin. Histology reveals a pseudolobular architecture with stellate to spindle-shaped cells in a myxoid stroma, and osteoclast-like giant cells at the lobule peripheries. What is the diagnosis?

Explanation

Chondromyxoid fibroma (CMF) is a rare benign bone tumor typically presenting as an eccentric, expansile metaphyseal lesion with a sclerotic, scalloped rim. Histologically, it has a classic pseudolobular pattern with stellate cells in a myxoid background, and hypercellular peripheries containing giant cells.

Question 77

A patient diagnosed with polyostotic fibrous dysplasia presents with a newly discovered, painless, deep soft tissue mass in the thigh. Excisional biopsy of the mass reveals a well-circumscribed lesion composed of bland spindle cells in an abundant myxoid stroma with decreased vascularity. The presence of this soft tissue lesion in conjunction with fibrous dysplasia is known as:

Explanation

Mazabraud syndrome is a rare disorder characterized by the association of fibrous dysplasia (usually polyostotic) and one or more intramuscular myxomas. McCune-Albright involves fibrous dysplasia, precocious puberty, and cafe-au-lait spots.

Question 78

A 28-year-old female presents with a painless mass behind her knee. Radiographs reveal a densely ossified mass attached to the posterior cortex of the distal femur by a broad base, with a radiolucent cleft between the tumor and the underlying bone cortex (string sign). Molecular analysis of this tumor is most likely to reveal an amplification of which of the following?

Explanation

The presentation is classic for a parosteal osteosarcoma (surface, low-grade, posterior distal femur, 'string sign'). Genetically, parosteal osteosarcomas (and low-grade central osteosarcomas) are characterized by supernumerary ring chromosomes containing amplifications of the 12q13-15 region, which includes the MDM2 and CDK4 genes.

Question 79

A 45-year-old male presents with generalized bone pain, severe muscle weakness, and multiple insufficiency fractures. Laboratory studies reveal severe hypophosphatemia, hyperphosphaturia, and low 1,25-dihydroxyvitamin D levels. A small soft tissue mass is incidentally found in his plantar fascia. The mass is resected, and his metabolic abnormalities resolve completely. The tumor most likely secreted which of the following substances?

Explanation

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome typically caused by a phosphaturic mesenchymal tumor. These tumors overproduce FGF23, which acts on the kidneys to decrease phosphate reabsorption and decrease 1-alpha-hydroxylase activity (lowering active Vitamin D), resulting in profound hypophosphatemia and osteomalacia.

Question 80

A 40-year-old male undergoes wide excision of a deep thigh mass, which is diagnosed histologically as a myxoid liposarcoma (t(12;16) translocation). Unlike most soft tissue sarcomas of the extremities, which primarily metastasize to the lungs, myxoid liposarcoma has a uniquely high propensity to metastasize to which of the following locations?

Explanation

Myxoid liposarcoma has a well-known, unique propensity for extrapulmonary metastasis, specifically to the skeletal system (especially the spine), often before pulmonary metastases occur. Staging should include whole-spine MRI or bone scintigraphy/PET-CT to rule out bony disease.

Question 81

A 28-year-old female presents with a painless mass on the posterior aspect of her distal thigh. Radiographs show a densely ossified mass attached to the posterior femoral cortex with a broad base and no medullary involvement. Which genetic amplification is most specific to this lesion?

Explanation

Parosteal osteosarcoma typically presents as a densely ossified mass on the posterior distal femur. It is a low-grade surface osteosarcoma characterized by a ring chromosome 12p leading to MDM2 and CDK4 amplification.

Question 82

A 35-year-old male is diagnosed with a giant cell tumor of the proximal tibia that is deemed surgically unresectable. Systemic therapy with denosumab is initiated. What is the specific mechanism of action of this medication in treating this tumor?

Explanation

Denosumab is a monoclonal antibody that binds to RANK ligand (RANKL). The neoplastic mononuclear cells in GCT secrete RANKL, which recruits and differentiates reactive osteoclast-like giant cells that cause bone destruction.

Question 83

A 24-year-old male presents with a slowly enlarging, painless mass near his knee joint. MRI reveals a deep soft-tissue mass adjacent to the joint capsule with small areas of calcification. Biopsy confirms a malignant biphasic tumor. Which chromosomal abnormality is diagnostic?

Explanation

Synovial sarcoma frequently occurs in young adults near large joints and can exhibit calcifications. The pathognomonic chromosomal translocation is t(X;18)(p11;q11), creating the SYT-SSX fusion gene.

Question 84

A 65-year-old male with a history of renal cell carcinoma presents with a painful destructive lesion in his subtrochanteric femur. Mirels' score is 10. Prophylactic fixation is planned. What is the most critical step prior to surgical intervention?

Explanation

Renal cell carcinoma and thyroid carcinoma metastases to bone are highly vascular. Preoperative selective arterial embolization is critical to minimize life-threatening intraoperative blood loss.

Question 85

A 55-year-old male presents with bowel and bladder dysfunction and sacral pain. Imaging reveals a midline destructive sacral lesion. Histology shows physaliferous cells with vacuolated cytoplasm. Which immunohistochemical marker is highly specific for this diagnosis?

Explanation

Chordoma is a locally aggressive tumor arising from notochordal remnants, typically occurring in the sacrum or clivus. Brachyury is a transcription factor critical for notochord development and is highly sensitive and specific for chordomas.

Question 86

A 9-year-old boy sustains a pathologic fracture through a radiolucent lesion in the proximal humerus with a "fallen leaf" sign. Radiographs show the lesion is located 2 cm distal to the open physis. What is the best initial management of the underlying lesion once the fracture has healed?

Explanation

This is a latent unicameral bone cyst (UBC), as it has migrated away from the physis. For symptomatic or structurally compromising UBCs, minimally invasive treatment like aspiration and injection of corticosteroids or bone marrow aspirate is the preferred initial management.

Question 87

An 18-year-old female presents with a rapidly expanding, painful lytic lesion in her distal fibula. MRI shows an expansile lesion with multiple fluid-fluid levels. Genetic analysis reveals a characteristic rearrangement. Which gene is primarily involved?

Explanation

Primary aneurysmal bone cysts (ABCs) are benign but locally aggressive neoplasms driven by USP6 gene rearrangements. MRI typically shows characteristic fluid-fluid levels indicating blood components of varying ages.

Question 88

A 32-year-old male presents with an anterior tibial bowing deformity and pain. Radiographs reveal a multiloculated, expansile, eccentric intracortical radiolucency in the tibial diaphysis. Histology shows biphasic spindle and epithelial cells. What is the most appropriate definitive surgical treatment?

Explanation

Adamantinoma is a low-grade malignant bone tumor that almost exclusively occurs in the tibial diaphysis. Because it is resistant to radiation and chemotherapy, wide surgical resection with segmental reconstruction is the standard of care to prevent local recurrence.

Question 89

A 68-year-old female complains of generalized bone pain and fatigue. Radiographs show multiple "punched-out" lytic lesions in her skull and pelvis. A bone scan shows no increased uptake in these areas. Which of the following laboratory findings is most likely to confirm the diagnosis?

Explanation

Multiple myeloma frequently presents with punched-out lytic bone lesions that are characteristically "cold" on technetium bone scans due to osteoblast suppression. Diagnosis is confirmed by demonstrating a monoclonal paraprotein spike on serum or urine protein electrophoresis.

Question 90

A 30-year-old female presents with a recurrently swollen, painless knee. Joint aspiration yields dark brown fluid. MRI demonstrates a villous synovial proliferation with blooming artifact on gradient-echo sequences. Which targeted therapy acts on the driving mutation for this condition?

Explanation

Pigmented villonodular synovitis (PVNS/TGCT) is driven by a t(1;2) translocation causing overexpression of CSF1. Pexidartinib is a CSF1 receptor inhibitor approved for severe, symptomatic TGCT not amenable to improvement with surgery.

Question 91

A 50-year-old male undergoes wide resection of a high-grade pleomorphic sarcoma of the thigh. He receives preoperative radiation therapy. Compared to postoperative radiation, preoperative radiation is associated with which of the following?

Explanation

Preoperative radiation therapy for soft tissue sarcomas uses a lower total dose and has less long-term tissue fibrosis compared to postoperative radiation. However, it is strongly associated with a significantly higher rate of acute postoperative wound complications.

Question 92

A 14-year-old boy presents with chronic knee pain. Radiographs reveal a well-circumscribed, 2 cm lytic lesion in the proximal tibial epiphysis with a thin sclerotic margin and central calcifications. What is the most common histological finding associated with this tumor?

Explanation

Chondroblastoma is a rare benign cartilage tumor characteristically arising in the epiphysis of skeletally immature patients. Histology typically shows chondroblasts, multinucleated giant cells, and fine pericellular "chicken-wire" calcifications.

Question 93

A 45-year-old male has a large, deep mass in his thigh. Core biopsy confirms myxoid liposarcoma. Which chromosomal translocation is classically associated with this tumor, and where is the most common site of metastasis?

Explanation

Myxoid liposarcoma is characterized by the t(12;16) translocation (FUS-DDIT3 fusion). Unlike most other soft tissue sarcomas that metastasize primarily to the lungs, myxoid liposarcoma has a unique propensity to metastasize to extrapulmonary sites, notably the spine and other bones.

Question 94

A 19-year-old male presents with persistent, dull aching back pain that is worse at night. The pain is not relieved by ibuprofen. CT imaging reveals a 2.5 cm radiolucent nidus with surrounding sclerosis in the posterior elements of L4. What is the most likely diagnosis?

Explanation

Osteoblastoma is histologically similar to osteoid osteoma but is distinguished clinically by a nidus larger than 1.5-2.0 cm. Additionally, the pain from osteoblastoma is typically less responsive to NSAIDs compared to osteoid osteoma.

Question 95

A 10-year-old girl is evaluated for multiple bony deformities and multiple subcutaneous soft-tissue hemangiomas. Radiographs show multiple cartilaginous lesions within the medullary cavity of her tubular bones. She is at highest risk for developing which of the following malignancies?

Explanation

This clinical presentation describes Maffucci syndrome, characterized by multiple enchondromas and soft-tissue hemangiomas. Patients have a nearly 100% lifetime risk of malignant transformation, most commonly to chondrosarcoma.

Question 96

A 20-year-old male presents with swelling over the anterior mid-tibia. Imaging reveals a surface lesion with sunburst periosteal reaction, cortical thickening, and no intramedullary involvement. Biopsy shows an intermediate-grade tumor with predominantly chondroblastic matrix. What is the appropriate treatment?

Explanation

Periosteal osteosarcoma is an intermediate-grade surface osteosarcoma that predominantly produces a chondroblastic matrix. Because of its intermediate grade and higher risk of metastasis compared to parosteal variants, standard treatment includes neoadjuvant chemotherapy followed by wide surgical resection.

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