Orthopedic Oncology/Tum Review | Dr Hutaif Orthopedic O -...

Question 1

A 28-year-old male presents with a deep, enlarging soft tissue mass in the anterior thigh. An MRI suggests a soft tissue sarcoma. Which of the following is a critical oncologic principle when performing an open incisional biopsy of this mass?

Explanation

Biopsy tracts for suspected sarcomas must be placed longitudinally and directly in line with the definitive surgical incision. This ensures the entire biopsy tract can be excised en bloc with the tumor during definitive wide resection. Transverse incisions contaminate wider margins. Drains must exit directly in line with the incision within the planned resection field. Tourniquets, if used, should be deflated prior to closure to ensure absolute hemostasis, preventing post-operative hematoma which can contaminate adjacent compartments.

Question 2

A 32-year-old female undergoes curettage and cementing of a giant cell tumor of the proximal tibia. Recurrence occurs 18 months later, with massive joint destruction precluding joint salvage. Neoadjuvant treatment is planned prior to an intra-articular resection. What is the mechanism of action of the targeted medical therapy typically used in this scenario?

Explanation

Denosumab is a fully human monoclonal antibody that binds to RANK-Ligand (RANKL), preventing it from binding to the RANK receptor on the surface of osteoclast precursors. In Giant Cell Tumor of Bone (GCTB), the neoplastic mononuclear stromal cells overexpress RANKL, which recruits and activates the reactive multinucleated giant cells that cause massive osteolysis. By inhibiting RANKL, denosumab halts bone destruction and promotes ossification of the tumor.

Question 3

A 14-year-old boy presents with a diaphysial tibial lesion characterized radiographically by a 'hair-on-end' periosteal reaction. Core biopsy reveals sheets of small round blue cells staining positive for CD99. Cytogenetic analysis is most likely to reveal which of the following translocations?

Explanation

Ewing sarcoma classically presents in the diaphysis of long bones in children and young adults. It is associated with the t(11;22)(q24;q12) translocation in over 85% of cases, resulting in the EWS-FLI1 fusion protein. Synovial sarcoma is associated with t(X;18) (SYT-SSX). Myxoid liposarcoma has t(12;16) (FUS-DDIT3). Alveolar rhabdomyosarcoma has t(2;13) (PAX3-FOXO1a). Extraskeletal myxoid chondrosarcoma has t(9;22).

Question 4

A 25-year-old male presents with a slowly growing, painless mass near the popliteal fossa. Radiographs show a soft tissue mass with stippled calcifications. MRI demonstrates a heterogeneous mass adjacent to, but distinct from, the knee joint capsule. Histology demonstrates a biphasic pattern of epithelial and spindle cells. What is the characteristic genetic translocation associated with this diagnosis?

Explanation

The scenario describes synovial sarcoma, which typically occurs in young adults (15-40 years) and presents as a slow-growing mass near a joint (most commonly the knee), though it rarely involves the synovium directly. Up to 30% show calcification on radiographs. The pathognomonic translocation is t(X;18)(p11;q11), leading to the SYT-SSX fusion gene.

Question 5

A 55-year-old male presents with severe mechanical pelvic pain. Pelvic radiographs and CT show a large, destructive lesion in the ilium with ring-and-arc calcifications and prominent cortical breakthrough. Core needle biopsy confirms a Grade 2 conventional chondrosarcoma. Which of the following is the most appropriate primary treatment modality?

Explanation

Conventional chondrosarcoma (Grade 2 and 3) is historically known to be resistant to both chemotherapy and radiation therapy due to its poor vascularity, low fraction of dividing cells, and abundant cartilaginous matrix. The mainstay of treatment is wide surgical excision. Intralesional curettage is reserved for benign cartilaginous lesions (enchondromas) or select Grade 1 atypical cartilaginous tumors in the appendicular skeleton, not for Grade 2 pelvic lesions.

Question 6

A 16-year-old girl undergoes 10 weeks of neoadjuvant multi-agent chemotherapy for an Enneking Stage IIB conventional osteosarcoma of the distal femur. She subsequently undergoes a limb-salvage distal femoral replacement. Which of the following is the most significant independent prognostic factor for her long-term overall survival?

Explanation

In conventional high-grade osteosarcoma, the histologic response to neoadjuvant chemotherapy, determined by the percentage of tumor necrosis in the resected specimen, is the single most important prognostic factor for long-term overall survival. Greater than 90% necrosis (Huvos grade III or IV) is considered a 'good' response and correlates with significantly higher survival rates compared to a poor response (<90% necrosis).

Question 7

A 62-year-old male with a history of clear cell renal cell carcinoma presents with progressive right arm pain. Radiographs reveal a large, purely lytic, destructive lesion in the humeral diaphysis with a Mirels' score of 10, indicating impending pathologic fracture. Prophylactic surgical stabilization is planned. Which of the following preoperative interventions is most highly recommended to minimize intraoperative morbidity?

Explanation

Metastatic renal cell carcinoma and thyroid carcinoma lesions are notoriously hypervascular. Extensive, sometimes life-threatening intraoperative hemorrhage is a major risk during orthopedic stabilization of these lesions. Preoperative percutaneous transarterial embolization, ideally performed 24-48 hours prior to surgery, significantly reduces intraoperative blood loss and associated morbidity.

Question 8

A 68-year-old female presents with severe back pain. Radiographs show multiple 'punched-out' lytic lesions in the skull and vertebral bodies. Laboratory testing reveals hypercalcemia and an M-spike on serum protein electrophoresis. The extensive osteolysis in this disease is primarily mediated by the interaction between myeloma cells and the bone microenvironment. Which specific mechanism is responsible for osteoclast overactivation in this condition?

Explanation

In Multiple Myeloma, the myeloma cells secrete macrophage inflammatory protein-1 alpha (MIP-1 alpha) and upregulate RANK-Ligand (RANKL) expression by marrow stromal cells, while simultaneously decreasing Osteoprotegerin (OPG). This creates a high RANKL/OPG ratio, shifting the balance heavily toward osteoclastogenesis and causing extensive lytic lesions. Bone formation is also suppressed via DKK-1 inhibition of the Wnt pathway.

Question 9

A 42-year-old male is diagnosed with myxoid liposarcoma of the proximal thigh following a core needle biopsy. The cytogenetics report confirms a t(12;16) translocation. In addition to a standard chest CT for staging, which imaging modality is uniquely indicated for staging this specific histologic subtype of soft tissue sarcoma?

Explanation

Myxoid liposarcoma (associated with the t(12;16) FUS-DDIT3 translocation) has a unique propensity to metastasize to extrapulmonary soft tissue and osseous sites, particularly the spine, before or even without lung involvement. Therefore, screening the whole spine (and often the pelvis/abdomen) with MRI is specifically recommended during staging for this subtype, unlike most other soft tissue sarcomas where chest CT is the primary staging tool.

Question 10

A 38-year-old male presents with chronic, mild right shoulder pain. Radiographs demonstrate a well-marginated lytic lesion within the epiphysis of the proximal humerus with subtle internal calcifications. Histology from a biopsy shows cells with abundant clear cytoplasm and distinct cell boundaries, dispersed among areas of hyaline cartilage, alongside occasional multinucleated giant cells. What is the most likely diagnosis?

Explanation

The location (epiphyseal) and imaging can mimic chondroblastoma or Giant Cell Tumor. However, chondroblastoma typically occurs in skeletally immature patients (teens). Clear cell chondrosarcoma is a rare, low-grade malignant tumor that preferentially occurs in the epiphyses of long bones in adult males (3rd to 5th decades). Histology shows characteristic 'clear cells' with distinct margins and central nuclei interspersed with hyaline cartilage.

Question 11

A 24-year-old male presents with a long-standing anterior bowing deformity of the tibia and recent onset of dull pain. Radiographs show a well-defined, multilocular, eccentric, 'soap-bubble' osteolytic lesion in the anterior cortex of the tibial diaphysis. Biopsy reveals a biphasic tumor consisting of epithelial cells arranged in nests and a surrounding bland, spindle-cell fibrous stroma. What is the most appropriate management?

Explanation

The clinical presentation and biphasic histology (epithelial nests within a fibrous stroma) in the anterior tibial cortex are pathognomonic for adamantinoma. Adamantinoma is a low-grade, slow-growing malignant primary bone tumor. Unlike osteofibrous dysplasia (which occurs in younger children and can resemble it), adamantinoma has metastatic potential. Standard treatment is wide surgical resection; it is resistant to chemotherapy and radiation, and curettage has a very high recurrence rate.

Question 12

A 58-year-old male presents with a 6-month history of worsening constipation and perianal numbness. Digital rectal examination reveals a firm, palpable presacral mass. An MRI demonstrates a large, lobulated destructive mass involving the S2-S4 sacral segments with profound T2 hyperintensity. CT-guided core biopsy shows large cells with abundant vacuolated cytoplasm arranged in cords. Which immunohistochemical marker is highly sensitive and specific for confirming this tumor?

Explanation

The tumor described is a sacral chordoma, which arises from notochordal remnants. The classic histologic finding is the 'physaliferous cell' containing abundant vacuolated cytoplasm. Brachyury, a transcription factor vital in notochordal development, is a highly sensitive and specific nuclear immunohistochemical marker for chordoma, which helps distinguish it from chondrosarcoma and other sacral mimics.

Question 13

A 30-year-old female presents with a painless, hard mass on the posterior aspect of her distal thigh. Radiographs demonstrate a densely ossified mass attached to the posterior cortex of the distal femur by a broad base, with no medullary involvement seen on MRI. Biopsy shows well-formed woven bone trabeculae separated by a low-grade spindle cell stroma. Which genetic alteration is a hallmark of this condition?

Explanation

The clinical and radiographic presentation describes a parosteal osteosarcoma, a low-grade surface osteosarcoma typically found on the posterior aspect of the distal femur. Histologically, it features well-formed woven bone and a bland fibroblastic stroma. The hallmark molecular finding is amplification of the MDM2 and CDK4 genes on chromosome 12q13-15.

Question 14

A 65-year-old female presents with a rapidly enlarging, painful mass in her right shoulder. She has a history of right breast cancer treated with lumpectomy and local adjuvant radiation therapy 12 years ago. Radiographs show an aggressive, moth-eaten lytic lesion destroying the body of the scapula with an associated large soft tissue mass. What is the most common histologic subtype of post-radiation primary bone sarcoma?

Explanation

Radiation-induced sarcomas of bone are rare but devastating late complications of radiation therapy, typically occurring with a latency of 5 to 15 years (often much longer). They are virtually always high-grade. Osteosarcoma is the most common histologic type of secondary, radiation-induced bone sarcoma, followed closely by fibrosarcoma/undifferentiated pleomorphic sarcoma (UPS).

Question 15

A 22-year-old female presents with a painless, slow-growing, highly vascular mass in her left deep anterior thigh. Her primary complaint, however, is a recent onset of severe headaches and left-sided visual field deficits. A staging brain MRI confirms a hemorrhagic solitary metastasis in the right occipital lobe. What is the most likely soft tissue sarcoma diagnosis?

Explanation

Alveolar soft part sarcoma (ASPS) is a rare, highly vascular, slow-growing tumor typically found in the deep tissues of the thigh in young adults. It is notorious for early, wide hematogenous dissemination, with a distinct propensity to metastasize to the brain (up to 30% of cases), which is highly unusual for other soft tissue sarcomas. It is associated with the t(X;17) ASPSCR1-TFE3 translocation.

Question 16

A 9-year-old boy incidentally undergoes radiography for mild shoulder pain, revealing a centrally located, well-circumscribed, purely lytic lesion in the proximal humeral metaphysis. An MRI demonstrates a single fluid-filled cavity with no fluid-fluid levels. During a diagnostic aspiration, clear yellow fluid is obtained. Which of the following is true regarding the biochemical fluid contents of this specific lesion?

Explanation

The lesion described is a Unicameral Bone Cyst (UBC), which typically yields clear, yellowish serous fluid upon aspiration. Analysis of UBC fluid demonstrates high levels of bone-resorbing factors, specifically prostaglandins (such as PGE2) and inflammatory cytokines like Interleukin-1 (IL-1), IL-6, and nitrogen oxides. This local biochemical environment promotes osteoclast activation and cyst expansion.

Question 17

A 70-year-old male with a history of advanced prostate cancer presents with severe low back pain. Radiographs demonstrate widespread blastic metastases in the lumbar spine and pelvis. The osteoblastic nature of prostate cancer bone metastases is primarily driven by the secretion of which of the following factors by the tumor cells?

Explanation

Prostate cancer uniquely causes predominantly osteoblastic (bone-forming) metastases. Prostate cancer cells secrete Endothelin-1 (ET-1), which strongly stimulates osteoblast proliferation and new bone formation, while concurrently suppressing osteoclast activity. This heavily contrasts with breast and lung cancers, which typically secrete PTHrP, promoting RANKL expression and causing osteolytic lesions.

Question 18

A 26-year-old male presents with a firm, painless nodule on the volar aspect of his distal right forearm that has slowly enlarged over 2 years. He previously had similar nodules locally excised, which were misdiagnosed as deep necrotizing granulomas, but they rapidly recurred. Physical exam shows focal ulceration of the overlying skin. What is the most characteristic secondary mode of dissemination for this specific sarcoma subtype?

Explanation

The clinical picture of a distal extremity nodule in a young adult that mimics a granuloma, ulcerates the skin, and spreads proximally is classic for epithelioid sarcoma. Notably, epithelioid sarcoma has a significantly higher rate of regional lymph node metastasis compared to most other soft tissue sarcomas (up to 30-40%), necessitating careful evaluation (often PET or sentinel node biopsy) of the draining lymph node basins.

Question 19

A 19-year-old male presents with chronic, dull back pain that profoundly worsens at night. He notes that naproxen provides significant, albeit temporary, relief. CT scan reveals a 3.0 cm lytic defect in the posterior elements of L3, surrounded by extensive sclerosis. Histologically, the lesion consists of interconnecting woven bone trabeculae lined by prominent single layers of osteoblasts with a vascular stroma. Based on the overall presentation and imaging, what is the most likely diagnosis?

Explanation

Osteoid osteoma and osteoblastoma share identical histologic features (woven bone trabeculae lined by prominent osteoblasts). They are differentiated primarily by size: osteoid osteomas are less than 1.5 - 2.0 cm in diameter, whereas osteoblastomas are larger (> 2.0 cm). Osteoblastomas also have a strong predilection for the posterior elements of the spine. While both can cause pain responsive to NSAIDs (due to prostaglandin production), the large size (3.0 cm) defines this as an osteoblastoma.

Question 20

According to the Musculoskeletal Tumor Society (MSTS) / Enneking staging system for benign bone tumors, an active benign tumor (Stage 2) is best described radiographically by which of the following findings?

Explanation

In the Enneking staging system for benign tumors: Stage 1 (Latent) tumors are well-marginated with a thick sclerotic rim, showing no active growth (e.g., non-ossifying fibroma). Stage 2 (Active) tumors exhibit symptomatic growth, possess a thin but continuous reactive margin, and often expand the bone but remain contained within the periosteum (e.g., ABC, UBC). Stage 3 (Aggressive) tumors have indistinct margins, cortical breakthrough, and can form a soft tissue component (e.g., Giant Cell Tumor).

Question 21

A 45-year-old male presents with a suspected high-grade sarcoma in the distal thigh. A core needle biopsy is planned. Which of the following is an absolute requirement for the biopsy tract?

Explanation

Biopsy tracts are considered contaminated and must be placed in a line that allows full excision en bloc with the tumor during definitive surgery. Longitudinal incisions are standard in the extremities to facilitate this.

Question 22

A 16-year-old girl is diagnosed with conventional osteosarcoma of the distal femur. Histology shows malignant spindle cells producing osteoid. Mutation in which of the following tumor suppressor genes is most strongly associated with her condition and a high risk of developing secondary malignancies like breast cancer?

Explanation

TP53 mutations are associated with Li-Fraumeni syndrome, which increases the risk for osteosarcoma, breast cancer, and other malignancies. RB1 mutations also predispose to osteosarcoma but are classically associated with retinoblastoma.

Question 23

A 40-year-old male presents with a painful lytic lesion in the proximal femoral epiphysis. Biopsy reveals cells with abundant clear cytoplasm, distinct borders, and scattered multinucleated giant cells. What is the most appropriate definitive treatment?

Explanation

The presentation and histology describe clear cell chondrosarcoma, a low-grade malignant tumor that uniquely affects the epiphysis. Treatment is wide surgical resection, as it is relatively resistant to chemotherapy and radiation.

Question 24

A 60-year-old male presents with an impending pathologic fracture of the proximal humerus secondary to metastatic renal cell carcinoma. Prophylactic stabilization is planned. Which of the following preoperative interventions is most critical to reduce perioperative morbidity?

Explanation

Renal cell carcinoma and thyroid carcinoma metastases are notoriously hypervascular. Preoperative selective arterial embolization significantly decreases intraoperative blood loss and perioperative morbidity.

Question 25

A 55-year-old male presents with bowel and bladder dysfunction. Imaging reveals a large, destructive midline sacral mass. Histological examination shows cells with abundant bubbly cytoplasm arranged in cords. Immunohistochemistry will most likely be positive for which of the following markers?

Explanation

The patient has a chordoma, characterized by physaliferous (bubbly) cells. Brachyury is a highly sensitive and specific immunohistochemical nuclear marker for chordoma, differentiating it from chondrosarcoma.

Question 26

A 65-year-old male undergoes marginal excision of a large, deep, fatty thigh mass initially thought to be a lipoma. Pathology reveals an atypical lipomatous tumor (well-differentiated liposarcoma). Amplification of which gene region is the molecular hallmark of this tumor?

Explanation

Atypical lipomatous tumors (well-differentiated liposarcomas) are characterized by the amplification of the 12q13-15 chromosomal region. This leads to the overexpression of MDM2 and CDK4, which can be identified by FISH or immunohistochemistry.

Question 27

A 9-year-old girl presents with a pathologic fracture of the proximal femur with a "shepherd's crook" deformity. She also has precocious puberty and cafe-au-lait spots with irregular borders. The underlying pathophysiology involves a post-zygotic activating mutation in which of the following?

Explanation

McCune-Albright syndrome consists of polyostotic fibrous dysplasia, endocrine abnormalities (e.g., precocious puberty), and cafe-au-lait spots. It is caused by a somatic activating mutation in the GNAS gene encoding the Gs alpha protein.

Question 28

A 25-year-old male presents with a slowly growing, painful mass near the knee joint. MRI shows a soft tissue mass adjacent to the joint capsule with focal calcifications. Biopsy shows a biphasic spindle cell neoplasm. What is the characteristic chromosomal translocation?

Explanation

Synovial sarcoma frequently presents in young adults near joints, often exhibiting focal calcifications on imaging. It is driven by the t(X;18)(p11;q11) translocation, resulting in the SS18-SSX fusion gene.

Question 29

A 68-year-old woman presents with generalized bone pain, anemia, and hypercalcemia. Skeletal survey reveals multiple punched-out lytic lesions in the skull and pelvis. Which of the following lab findings is most likely present?

Explanation

The patient's presentation is classic for multiple myeloma, defined by the CRAB criteria (hypercalcemia, renal failure, anemia, bone lesions). Diagnosis is supported by identifying a monoclonal (M) spike on serum or urine protein electrophoresis.

Question 30

A 30-year-old female presents with a painless, slowly enlarging mass on the posterior aspect of the distal femur. Radiographs demonstrate a dense, ossified mass attached to the posterior cortex with a radiolucent cleft between the tumor and underlying bone. What is the most appropriate management?

Explanation

Parosteal osteosarcoma is a low-grade surface osteosarcoma classically found on the posterior distal femur, featuring a "string sign" (radiolucent cleft). Because it is low grade, it does not typically require chemotherapy and is treated with wide surgical resection alone.

Question 31

A 14-year-old boy presents with knee pain. Radiographs reveal an eccentrically located, sharply marginated lytic lesion with stippled calcifications confined to the proximal tibial epiphysis. Histology shows polygonal cells with longitudinal nuclear grooves and pericellular calcification. What is the diagnosis?

Explanation

Chondroblastoma is a benign cartilage tumor that characteristically occurs in the epiphysis of skeletally immature patients. Histology classically shows chondroblasts with grooved nuclei ("coffee bean" nuclei) and "chicken-wire" pericellular calcification.

Question 32

A 20-year-old male complains of severe nocturnal back pain relieved by NSAIDs. Imaging reveals a 2.5 cm lytic lesion with surrounding sclerosis in the posterior elements of L4. What makes this lesion most likely an osteoblastoma rather than an osteoid osteoma?

Explanation

Both osteoid osteoma and osteoblastoma can occur in the posterior elements of the spine and cause pain. However, osteoblastomas are distinguished primarily by their larger size, typically defined as greater than 1.5 to 2.0 cm.

Question 33

A 50-year-old woman undergoes wide resection of a high-grade undifferentiated pleomorphic sarcoma of the thigh. The pathology report indicates a negative but narrow (< 1 mm) margin along a major motor nerve. The epineurium was left intact. Which of the following is the most appropriate next step in management?

Explanation

In the setting of a high-grade soft tissue sarcoma with close but negative margins on a critical structure (like a major nerve with an intact epineurium), adjuvant radiation therapy is indicated to optimize local control without causing major functional morbidity.

Question 34

An 8-year-old boy sustains a minor fall and presents with arm pain. X-rays show a pathologic fracture through a centrally located lytic lesion in the proximal humerus metaphysis. A "fallen leaf" sign is present. What is the most appropriate initial management of the fracture?

Explanation

A "fallen leaf" or "fallen fragment" sign is pathognomonic for a simple (unicameral) bone cyst. Pathologic fractures through a proximal humerus UBC are initially treated non-operatively with immobilization, which occasionally results in spontaneous healing of the cyst.

Question 35

A 12-year-old girl presents with a rapidly expanding, painful, eccentrically located lytic lesion in the distal femur. MRI reveals multiple fluid-fluid levels. Biopsy confirms an Aneurysmal Bone Cyst (ABC). Primary ABCs are often associated with a recurrent chromosomal translocation resulting in the upregulation of which gene?

Explanation

Primary aneurysmal bone cysts are now recognized as true neoplasms rather than reactive processes. They are driven by t(16;17) translocations that result in the upregulation of the USP6 gene.

Question 36

A 35-year-old female presents with a slow-growing, painful mass in her anterior tibial diaphysis. Radiographs show a multi-loculated, "soap-bubble" eccentric osteolytic lesion in the anterior cortex. Histology reveals epithelial cell islands in a fibrous stroma. What is the recommended treatment?

Explanation

Adamantinoma is a low-grade malignant bone tumor that almost exclusively occurs in the anterior tibial diaphysis and exhibits biphasic epithelial and fibrous features. It is resistant to radiation and chemotherapy, requiring wide surgical resection.

Question 37

A patient with an unresectable sacral giant cell tumor of bone (GCTB) is treated with denosumab. Denosumab exerts its therapeutic effect in this condition by binding to which of the following?

Explanation

In GCTB, the neoplastic mononuclear stromal cells secrete RANKL, which recruits and activates normal osteoclast-like giant cells causing bone destruction. Denosumab is a monoclonal antibody that binds directly to RANKL, preventing this interaction.

Question 38

A 15-year-old boy completes neoadjuvant chemotherapy for Ewing sarcoma of the fibula. He subsequently undergoes wide resection. Pathologic evaluation of the resected specimen is performed. Which of the following is the most significant prognostic factor for overall survival at this stage?

Explanation

In both osteosarcoma and Ewing sarcoma, the histologic response to neoadjuvant chemotherapy (quantified as the percentage of tumor necrosis in the resection specimen) is one of the most powerful prognostic indicators for overall survival.

Question 39

A 55-year-old woman with metastatic breast cancer presents with thigh pain. Radiographs reveal a mixed blastic and lytic lesion in the pertrochanteric region of the femur. According to Mirels' criteria, which of the following characteristics contributes the highest number of points toward the total score?

Explanation

Mirels' criteria assesses the risk of pathologic fracture based on site, pain, lesion nature, and size. A purely lytic lesion scores 3 points (the maximum for that category), whereas a blastic lesion scores 1 and mixed scores 2.

Question 40

A 19-year-old male with Multiple Hereditary Exostoses (MHE) notes a sudden increase in the size of a long-standing painless mass on his proximal medial tibia, now accompanied by pain. What is the most reliable MRI feature suggesting malignant transformation to secondary chondrosarcoma?

Explanation

Malignant transformation of an osteochondroma into a secondary chondrosarcoma is suspected when there is new pain or growth in a skeletally mature patient. On MRI, a cartilage cap thickness exceeding 1.5 to 2.0 cm is highly suggestive of malignancy.

Question 41

A 15-year-old boy presents with an enlarging, painful mass in his distal femur. Radiographs display a "sunburst" periosteal reaction and a Codman triangle. Core needle biopsy reveals malignant osteoid. Genetic testing of the tumor cells is most likely to show abnormalities in which of the following tumor suppressor genes?

Explanation

Osteosarcoma is strongly associated with mutations in the RB1 and TP53 tumor suppressor genes. Patients with Li-Fraumeni syndrome (germline TP53 mutation) and hereditary retinoblastoma (RB1 mutation) have a significantly increased risk of developing osteosarcoma.

Question 42

A 60-year-old male presents with a large, slow-growing pelvic mass. Imaging shows a lytic lesion with "popcorn" calcifications in the right ilium. Biopsy confirms a grade II (intermediate) chondrosarcoma. What is the most appropriate primary treatment modality?

Explanation

Conventional chondrosarcomas are generally resistant to both chemotherapy and radiation therapy. Wide surgical resection with negative margins is the primary and most effective treatment for intermediate and high-grade chondrosarcomas.

Question 43

A 22-year-old male presents with a 6-month history of a dull, aching pain in his posterior thoracic spine that is not relieved by aspirin. CT imaging reveals a 3.5 cm expansile, radiolucent lesion in the T8 posterior elements. What is the most likely diagnosis?

Explanation

Osteoblastoma typically presents in the posterior elements of the spine in young adults. It is histologically similar to osteoid osteoma but is distinguished by being larger (>2 cm), exhibiting progressive growth, and being less responsive to NSAIDs.

Question 44

A 65-year-old male with a history of nephrectomy for renal cell carcinoma presents with a destructive, lytic lesion of the proximal humerus and an impending fracture. Prophylactic stabilization with an intramedullary nail is planned. What critical step should be taken prior to surgery?

Explanation

Renal cell carcinoma and thyroid carcinoma metastases to bone are notoriously hypervascular. Preoperative arterial embolization is strongly recommended 24-48 hours before surgical stabilization to minimize the risk of massive intraoperative hemorrhage.

Question 45

A 30-year-old female presents with a slow-growing, painful mass deep in the plantar aspect of her foot. Biopsy reveals a biphasic tumor with both epithelial and spindle cell components. Which genetic translocation is diagnostic for this tumor?

Explanation

Synovial sarcoma is characterized by the t(X;18) translocation, resulting in the SYT-SSX fusion gene. It commonly presents as a deep seated mass in the extremities of young adults, often near joints but rarely intra-articular.

Question 46

A 14-year-old girl presents with a rapidly enlarging, painful mass in her proximal humerus. Radiographs show an eccentric, expansile radiolucent lesion. MRI demonstrates multiple fluid-fluid levels. If a primary neoplastic process is confirmed, which gene rearrangement is characteristic of this lesion?

Explanation

Primary aneurysmal bone cysts (ABCs) are now known to be true neoplasms driven by the USP6 (TRE17) gene rearrangement. While fluid-fluid levels on MRI are characteristic of ABCs, they can also be seen in telangiectatic osteosarcoma and giant cell tumors.

Question 47

A 16-year-old boy presents with chronic knee pain. Radiographs reveal a well-defined lytic lesion located exclusively within the epiphysis of the distal femur. Histology demonstrates mononuclear cells, osteoclast-like giant cells, and fine "chicken-wire" calcifications. What is the diagnosis?

Explanation

Chondroblastoma is a rare benign cartilage-producing tumor that characteristically arises in the epiphysis or apophysis of long bones in skeletally immature patients. Histology pathognomonically shows fine "chicken-wire" calcifications surrounding chondroblasts.

Question 48

A 10-year-old girl is found to have a diaphyseal femur fracture after a minor fall. Radiographs show a "shepherd's crook" deformity with an intramedullary "ground-glass" appearance. She also has precocious puberty and large café-au-lait spots. What is the underlying genetic mutation?

Explanation

McCune-Albright syndrome consists of polyostotic fibrous dysplasia, endocrine abnormalities (such as precocious puberty), and "coast of Maine" café-au-lait spots. It is caused by a somatic activating missense mutation in the GNAS gene.

Question 49

A 25-year-old male presents with chronic anterior tibial pain. Radiographs demonstrate a multilocular, eccentric, "soap-bubble" lytic lesion in the anterior diaphysis of the tibia. Biopsy reveals islands of epithelial cells within a dense fibrous stroma. What is the most appropriate management?

Explanation

Adamantinoma is a rare, low-grade malignant bone tumor that almost exclusively affects the anterior tibial diaphysis. Because it is largely resistant to radiation and chemotherapy, wide surgical resection with reconstruction is the gold standard treatment.

Question 50

A 65-year-old male presents with generalized bone pain and fatigue. Radiographs show multiple "punched-out" lytic lesions in his skull and pelvis. A technetium-99m bone scan shows decreased uptake in these affected areas. Laboratory tests reveal hypercalcemia. What is the most likely diagnosis?

Explanation

Multiple myeloma classically presents with multiple lytic "punched-out" bone lesions that are "cold" on a technetium bone scan due to a lack of reactive osteoblastic activity. Diagnostic criteria also include hypercalcemia, renal failure, and anemia (CRAB criteria).

Question 51

A 55-year-old male complains of chronic low back pain and recent onset of bowel incontinence. MRI reveals a large destructive mass centered in the sacrum. Biopsy shows lobules of vacuolated cells with a bubbly cytoplasm. From what embryonic structure does this tumor arise?

Explanation

Chordomas are rare, slow-growing malignant bone tumors that arise from the embryonic remnants of the notochord. They typically occur in the midline of the axial skeleton, most commonly in the sacrum and clivus, and feature pathognomonic "physaliferous" cells.

Question 52

A 12-year-old boy presents with multiple asymmetrical hard lumps on his hands. Exam reveals several bluish soft tissue nodules on his forearm. Radiographs show multiple expansile radiolucent lesions in the phalanges with stippled calcifications. What is this patient at highest risk of developing later in life?

Explanation

This presentation is classic for Maffucci syndrome, which is characterized by multiple enchondromas and soft tissue hemangiomas. Patients with Maffucci syndrome have a very high risk of malignant transformation, most commonly to secondary chondrosarcoma.

Question 53

A 45-year-old male presents with a painless, deep intramuscular mass in his thigh. Core biopsy reveals myxoid liposarcoma. Which of the following translocations is most strongly associated with this specific histology?

Explanation

Myxoid liposarcoma is characterized by the t(12;16)(q13;p11) translocation, which creates the FUS-DDIT3 fusion protein. The presence of a round cell component (>5%) indicates a higher-grade tumor and a significantly worse prognosis.

Question 54

An 8-year-old boy falls and sustains a proximal humerus fracture. Radiographs show a centrally located radiolucent lesion in the metaphysis extending to the physis, with a small piece of cortex lying at the bottom of the cyst. What is the preferred first-line treatment for this underlying lesion after the fracture heals?

Explanation

The "fallen leaf" sign is pathognomonic for a unicameral (simple) bone cyst. After allowing the pathologic fracture to heal, the first-line treatment for active, symptomatic cysts is typically an aspiration followed by a corticosteroid or bone marrow aspirate injection.

Question 55

A 24-year-old male presents with a deep, slow-growing mass in the popliteal fossa. Core needle biopsy demonstrates a biphasic tumor consisting of epithelial and spindle cells. Which of the following chromosomal translocations is most characteristic of this diagnosis?

Explanation

This patient has a synovial sarcoma, which characteristically features the t(X;18)(p11;q11) translocation resulting in the SYT-SSX fusion gene. This molecular marker is present in over 90% of synovial sarcomas.

Question 56

A 15-year-old boy completes neoadjuvant chemotherapy for conventional osteosarcoma of the distal femur and subsequently undergoes wide local excision. Which of the following variables is the most significant prognostic factor for long-term overall survival?

Explanation

The degree of tumor necrosis following neoadjuvant chemotherapy is the most critical prognostic indicator for overall survival in osteosarcoma. Greater than 90% necrosis indicates a good histologic response and significantly improved prognosis.

Question 57

A 55-year-old man presents with a large, destructive pelvic mass showing 'ring and arc' calcifications on plain radiography. Biopsy confirms a grade II conventional chondrosarcoma. What is the most appropriate management for this patient?

Explanation

Conventional chondrosarcoma is notoriously resistant to both chemotherapy and radiation therapy. The gold standard treatment for intermediate to high-grade chondrosarcoma of the pelvis is wide surgical resection with negative margins.

Question 58

An 18-year-old boy complains of nocturnal lower back pain that is completely relieved by ibuprofen. A CT scan reveals a 1 cm sclerotic lesion with a central radiolucent nidus in the L4 pedicle. What is the most appropriate initial minimally invasive treatment?

Explanation

The clinical presentation and imaging are classic for an osteoid osteoma. CT-guided radiofrequency ablation (RFA) is highly successful, minimally invasive, and is considered the treatment of choice for typical osteoid osteomas.

Question 59

A 65-year-old man presents with severe back pain and multiple lytic lesions in the axial skeleton on plain films. A technetium-99m bone scan shows no increased radiotracer uptake in these areas. What is the primary cellular mechanism driving bone destruction in this condition?

Explanation

This patient has multiple myeloma, characterized by 'cold' lesions on a bone scan due to a lack of osteoblastic bone formation. Myeloma cells upregulate RANKL and downregulate OPG, leading to severe osteoclast activation and pure lytic bone destruction.

Question 60

A 55-year-old woman with advanced breast cancer presents with progressively worsening right thigh pain. Radiographs reveal a 3.5 cm lytic lesion in the peritrochanteric region of the right femur, involving 60% of the cortical diameter. Her Mirels' score is 10. What is the most appropriate next step in management?

Explanation

A Mirels' score of 9 or greater indicates a high risk for impending pathologic fracture. Prophylactic internal fixation is indicated, followed by post-operative radiation to achieve local tumor control.

Question 61

A 12-year-old girl presents with pain and swelling of her left knee. MRI demonstrates an expansile, eccentric lytic lesion in the distal femur metaphysis containing multiple fluid-fluid levels. Genetic analysis of this lesion would most likely reveal which of the following alterations?

Explanation

The clinical and MRI findings (fluid-fluid levels) are diagnostic of an aneurysmal bone cyst (ABC). Primary ABCs are true neoplasms driven by a USP6 rearrangement, most commonly t(16;17).

Question 62

A 9-year-old boy experiences acute right shoulder pain after a minor fall. X-rays show a central, purely lytic lesion in the proximal humerus metaphysis extending to the physis, with a small piece of cortical bone resting at the dependent portion of the cyst. What is the most likely diagnosis?

Explanation

A central, lytic metaphyseal lesion in a child with a 'fallen leaf' sign (a fragment of fractured cortex at the bottom of the cyst) is pathognomonic for a fractured unicameral bone cyst (UBC).

Question 63

A 30-year-old woman undergoes excision of a slow-growing, deep mass in the plantar aspect of her foot. Histology demonstrates fascicles of uniform spindle cells with clear cytoplasm. Immunohistochemistry is strongly positive for S-100 and HMB-45. What is the most likely diagnosis?

Explanation

Clear cell sarcoma (melanoma of soft parts) typically arises in the deep soft tissues of the foot and ankle in young adults. It shows melanocytic differentiation and stains positive for S-100 and HMB-45, distinguishing it from synovial sarcoma.

Question 64

A 50-year-old man requires surgical resection and radiation therapy for a high-grade soft tissue sarcoma of the anterior thigh. When counseling the patient, you explain that preoperative radiation therapy, compared to postoperative radiation therapy, carries a significantly higher risk of which complication?

Explanation

Preoperative radiation therapy for soft tissue sarcomas is associated with a significantly higher rate of major acute wound healing complications (approx. 35%). However, it results in less long-term fibrosis, stiffness, and edema compared to postoperative radiation.

Question 65

A 35-year-old woman with an unresectable giant cell tumor of the sacrum is initiated on denosumab therapy. Which of the following best describes the expected histologic and radiographic response to this medication?

Explanation

Denosumab is a RANKL inhibitor that prevents the maturation of osteoclast-like giant cells. Treatment results in the rapid depletion of giant cells and the laying down of woven bone, appearing as dense central osteosclerosis on radiographs.

Question 66

A 10-year-old girl is evaluated for a limp. Radiographs demonstrate a 'ground-glass' expansile lesion with a 'shepherd's crook' deformity in the proximal femur. Physical exam reveals unilateral café-au-lait spots with irregular 'coast of Maine' borders. This syndrome is caused by a post-zygotic mutation in which gene?

Explanation

This patient has McCune-Albright syndrome, featuring polyostotic fibrous dysplasia, café-au-lait spots, and precocious puberty. It is caused by an activating missense mutation in the GNAS gene, which encodes the alpha subunit of the Gs protein.

Question 67

A 45-year-old man has a biopsy-proven myxoid liposarcoma of the left thigh. During the staging workup, in addition to evaluating the lungs, which anatomic area must be meticulously imaged due to this tumor's unique pattern of extrapulmonary metastasis?

Explanation

Myxoid liposarcoma has a distinct propensity to metastasize to extrapulmonary bone sites, particularly the spine. Whole-body MRI or a targeted MRI of the entire spine is recommended during the initial staging workup.

Question 68

A 25-year-old woman presents with a slow-growing, painless mass on the posterior distal femur. Radiographs reveal a densely ossified mass arising from the cortex with a radiolucent cleft separating the tumor from the underlying bone. What molecular alteration is highly specific to this tumor?

Explanation

The clinical and radiographic presentation ('string sign' or radiolucent cleft) is classic for parosteal osteosarcoma. This low-grade surface osteosarcoma is driven by the amplification of MDM2 and CDK4 on chromosome 12q13-15.

Question 69

A 42-year-old man is found to have an incidental cartilaginous lesion in the proximal humerus diaphysis. Which of the following radiographic features is the most reliable indicator of malignant transformation to a secondary chondrosarcoma?

Explanation

Differentiating an enchondroma from a low-grade chondrosarcoma relies heavily on radiographic features. Deep endosteal scalloping (more than 2/3 of the cortical thickness), cortical thickening, or cortical breakthrough are highly indicative of chondrosarcoma.

Question 70

A 22-year-old man presents with a slow-growing, painless nodular mass on the volar aspect of his wrist. Biopsy reveals atypical epithelioid cells with central necrosis, and immunohistochemistry shows loss of INI-1 (SMARCB1) expression. This tumor has a higher-than-average propensity to metastasize to which of the following sites?

Explanation

Epithelioid sarcoma typically affects the distal upper extremity of young adults and frequently demonstrates loss of INI-1. Unlike most soft tissue sarcomas, it has a notable propensity for regional lymph node metastasis.

Question 71

A 28-year-old man complains of a chronic, dull ache in his anterior leg. Radiographs reveal an eccentric, multi-loculated, 'soap-bubble' lytic lesion in the anterior tibial diaphysis. Histology shows nests of epithelial cells within a fibrous stroma. What is the most appropriate definitive management?

Explanation

The clinical, radiographic, and histologic findings (biphasic epithelial and fibrous tissue) are diagnostic of adamantinoma, a low-grade malignant bone tumor. It is resistant to radiation and chemotherapy, making wide surgical resection the standard of care.

Question 72

A 24-year-old male with known Multiple Hereditary Exostoses (MHE) reports recent pain and enlargement of a previously stable lesion on his proximal medial tibia. An MRI is obtained. Which of the following findings is most concerning for malignant transformation to a secondary chondrosarcoma?

Explanation

In a skeletally mature patient with an osteochondroma, a cartilage cap thicker than 1.5 to 2.0 cm on MRI is the most reliable imaging indicator of malignant transformation to a secondary chondrosarcoma.

Question 73

A 6-year-old boy presents with mid-back pain. Radiographs show complete collapse of the T8 vertebral body (vertebra plana). Needle biopsy demonstrates an infiltrate of histiocytes with grooved, 'coffee-bean' nuclei mixed with eosinophils. Electron microscopy of these cells would uniquely identify which structure?

Explanation

The presentation is classic for Langerhans Cell Histiocytosis (Eosinophilic Granuloma). The pathognomonic electron microscopy finding for Langerhans cells is the Birbeck granule, which has a distinct 'tennis-racket' shape.

Question 74

A 60-year-old man presents with progressive sacral pain and bowel dysfunction. MRI demonstrates a large, destructive midline sacral mass with high T2 signal. Biopsy reveals lobules of large, vacuolated 'physaliferous' cells within a myxoid stroma. Which immunohistochemical marker is highly sensitive and specific for this diagnosis?

Explanation

The patient has a chordoma, which classically arises in the sacrum or clivus and features physaliferous cells. Nuclear expression of the transcription factor brachyury is a highly sensitive and specific marker for chordoma.

Question 75

A 65-year-old man presents with a painful lytic lesion in the lesser trochanter. He has a history of a radical nephrectomy for renal cell carcinoma. He is planned for a prophylactic cephalomedullary nailing. What is the most critical pre-operative step to prevent intra-operative complications?

Explanation

Metastatic bone lesions from renal cell carcinoma and thyroid carcinoma are highly vascular. Pre-operative embolization is critical to significantly reduce the risk of massive, life-threatening intra-operative hemorrhage.

Question 76

A 16-year-old girl is diagnosed with a high-grade intramedullary osteosarcoma of the distal femur. Her family history is significant for a mother with early-onset breast cancer and a sibling with an adrenocortical carcinoma. A germline mutation in which of the following genes is most likely responsible for her condition?

Explanation

The clinical picture describes Li-Fraumeni syndrome, an autosomal dominant disorder caused by a germline mutation in the TP53 tumor suppressor gene. It carries a markedly increased risk of developing osteosarcoma, breast cancer, leukemia, and soft tissue sarcomas.

Question 77

A 34-year-old male presents with a slow-growing, deep-seated soft tissue mass in the plantar aspect of his foot. Radiographs demonstrate stippled calcifications within the soft tissues. Biopsy confirms a malignant spindle cell neoplasm. Which of the following translocations is diagnostic for this tumor?

Explanation

Synovial sarcoma frequently presents in young adults in the extremities, especially the foot and ankle, and often shows intralesional calcifications on radiographs. It is genetically characterized by the t(X;18)(p11;q11) translocation, which fuses the SYT and SSX genes.

Question 78

A 22-year-old female presents with multiple painless, hard masses on her hands. Examination reveals multiple soft tissue hemangiomas with phleboliths on her forearm and trunk. Radiographs of the hands show multiple expansile lytic lesions with rings-and-arcs calcifications in the phalanges. What is the patient's lifetime risk of malignant transformation of her bone lesions?

Explanation

The patient has Maffucci syndrome, characterized by multiple enchondromas and soft tissue hemangiomas. The lifetime risk of malignant transformation to chondrosarcoma or developing visceral malignancies is extremely high, often cited as approaching 100%.

Question 79

A 28-year-old male presents with chronic anterior shin pain. Radiographs reveal an eccentric, multi-locular, lytic lesion in the anterior tibial diaphysis with a soap-bubble appearance. Biopsy shows nests of cells with a biphasic pattern consisting of epithelial cells and osteofibrous stroma. Immunohistochemistry will most likely be positive for which of the following markers?

Explanation

Adamantinoma is a rare, low-grade malignant bone tumor with a strong predilection for the anterior tibial diaphysis. It is characterized by epithelial differentiation, making it reliably positive for epithelial markers such as cytokeratin and EMA.

Question 80

A 15-year-old boy presents with right shoulder pain. Radiographs show a well-circumscribed lytic lesion in the proximal humeral epiphysis with a thin sclerotic margin. Histology reveals polyhedral cells with grooved nuclei and areas of pericellular chicken-wire calcification. Which gene is most commonly mutated in this tumor?

Explanation

Chondroblastoma is a benign epiphyseal cartilage tumor uniquely characterized by chicken-wire calcifications. It is primarily driven by mutations in the H3F3B gene, distinguishing it from giant cell tumors which have H3F3A mutations.

Question 81

A 12-year-old girl is evaluated for a varus deformity of the proximal femur. Radiographs reveal a ground-glass appearance of the medullary canal. She also has unilateral café-au-lait spots with irregular borders. A mutation causing constitutive activation of the Gs-alpha protein (GNAS) is identified. What is the underlying histologic consequence of this mutation?

Explanation

Fibrous dysplasia, part of McCune-Albright syndrome when combined with endocrinopathies and café-au-lait spots, is caused by a GNAS mutation. This increases intracellular cAMP, impairing osteoblast differentiation and preventing the maturation of woven bone into lamellar bone.

Question 82

A 28-year-old female presents with a painless mass behind her knee. Radiographs reveal a dense, heavily ossified mass arising from the posterior cortex of the distal femur. There is no medullary involvement. Molecular analysis of the biopsy specimen is most likely to show amplification of which of the following?

Explanation

Parosteal osteosarcoma is a low-grade surface osteosarcoma typically found on the posterior aspect of the distal femur. Genetically, it is characterized by supernumerary ring chromosomes leading to the amplification of the MDM2 and CDK4 genes.

Question 83

A 45-year-old male is diagnosed with a myxoid liposarcoma of the deep posterior thigh. Genetic testing confirms a t(12;16) translocation. When staging this patient, in addition to standard chest imaging, what other imaging modality is critical due to this tumor's unique pattern of spread?

Explanation

Myxoid liposarcoma has a strong propensity to metastasize to extrapulmonary sites, particularly bone and the spine. Therefore, staging should include an MRI of the total spine and pelvis to detect these skip bone metastases.

Updated Orthopedic Review | Dr Hutaif General Orthopedi -...

Orthopedic Oncology/Tum Review | Dr Hutaif Orthopedic O -...

Key Takeaway

Orthopedic Oncology/Tum Review | Dr Hutaif Orthopedic O -...

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