ABOS Orthopedic Pathology Board Review MCQs | Part 1

Question 1

An 18-month-old child presents with anterolateral bowing of the left tibia and multiple café-au-lait spots. An X-ray is shown demonstrating the classic deformity. What is the underlying genetic mutation associated with this condition?

Explanation

Neurofibromatosis type 1 is associated with a mutation in the NF1 gene on chromosome 17, which encodes neurofibromin. Anterolateral bowing of the tibia is highly characteristic and often progresses to congenital pseudarthrosis.

Question 2

A 15-year-old boy is diagnosed with high-grade conventional osteosarcoma of the distal femur. After completing a course of neoadjuvant chemotherapy, he undergoes wide surgical resection. Which of the following is the most important prognostic factor for his long-term survival?

Explanation

The most critical prognostic factor for localized osteosarcoma is the histologic response to neoadjuvant chemotherapy. Greater than 90% tumor necrosis in the resected specimen is considered a good response and correlates with improved overall survival.

Question 3

A 12-year-old girl presents with a painful, swollen thigh and systemic symptoms including fever. Biopsy reveals small round blue cells expressing CD99. Which of the following chromosomal translocations is most characteristic of this lesion?

Explanation

Ewing sarcoma is a small round blue cell tumor typically characterized by the t(11;22)(q24;q12) translocation, resulting in the EWS-FLI1 fusion protein. CD99 (MIC2) is strongly positive on immunohistochemistry.

Question 4

A 55-year-old man presents with deep thigh pain. Imaging reveals a large, lobulated medullary lesion in the proximal femur with "rings and arcs" calcification. Biopsy confirms a grade II chondrosarcoma. What is the most appropriate management?

Explanation

Grade II and III chondrosarcomas require wide surgical resection because they are largely resistant to conventional chemotherapy and radiation. Intralesional curettage is reserved for grade I (atypical cartilaginous tumors) in the appendicular skeleton.

Question 5

A 32-year-old woman presents with knee pain. Radiographs show an eccentric, lytic epiphyseal-metaphyseal lesion of the distal femur extending to the subchondral bone. Biopsy shows multinucleated giant cells in a background of mononuclear stroma. Before surgical curettage, the multidisciplinary team recommends a targeted medical therapy. What is the mechanism of action of the most commonly used agent?

Explanation

Giant Cell Tumor (GCT) of bone is often treated with denosumab, a monoclonal antibody that binds to RANKL, inhibiting the differentiation and activation of osteoclast-like giant cells. This is particularly useful for downsizing tumors near articular surfaces prior to surgery.

Question 6

A 19-year-old male complains of right thigh pain that is worse at night and dramatically improves with ibuprofen. A CT scan reveals a 7-mm radiolucent nidus surrounded by dense sclerotic bone in the femoral diaphysis. What is the most appropriate definitive treatment?

Explanation

Osteoid osteoma classically presents with nocturnal pain relieved by NSAIDs due to high prostaglandin production by the nidus. Radiofrequency ablation (RFA) is the current gold standard definitive treatment, offering high success rates with minimal morbidity.

Question 7

A 10-year-old girl is evaluated for a shepherd's crook deformity of her proximal femur. Radiographs show a "ground-glass" appearance of the medullary canal. She also has precocious puberty and large café-au-lait macules with irregular borders. What is the underlying genetic mutation?

Explanation

McCune-Albright syndrome consists of polyostotic fibrous dysplasia, café-au-lait spots with irregular "coast of Maine" borders, and endocrine abnormalities. It is caused by a somatic activating mutation in the GNAS1 gene, which increases intracellular cAMP.

Question 8

An 8-year-old boy falls and sustains a mild injury to his right shoulder. X-rays reveal a centrally located, completely lytic lesion in the proximal humerus metaphysis with a piece of cortical bone resting at the dependent portion of the lesion. He has a minimally displaced pathological fracture. What is the best initial management?

Explanation

The "fallen leaf" sign is pathognomonic for a Unicameral Bone Cyst (UBC). When a UBC presents with a pathological fracture, the initial treatment is to immobilize the limb to allow the fracture to heal, which occasionally leads to spontaneous obliteration of the cyst.

Question 9

A 65-year-old man presents with persistent back pain and fatigue. Blood tests reveal anemia, hypercalcemia, and an elevated creatinine. A serum protein electrophoresis demonstrates a monoclonal spike. Which imaging modality is most sensitive for detecting early impending pathologic fractures in this patient's long bones?

Explanation

Multiple myeloma often results in purely lytic bone lesions that may not be active on a traditional Technetium-99m bone scan due to lack of osteoblastic response. Whole-body low-dose CT or MRI is currently favored over standard skeletal surveys for superior sensitivity in detecting lytic lesions.

Question 10

A 58-year-old woman with a history of breast cancer presents with left hip pain. Radiographs demonstrate a 3.5 cm lytic lesion in the peritrochanteric region of the left femur, involving >50% of the cortex. She reports pain with weight-bearing. According to Mirels' criteria, what is the most appropriate management?

Explanation

This patient has a Mirels' score of at least 10 (Site: lower limb=3, Pain: functional/weight-bearing=3, Lesion: lytic=3, Size: >2/3 cortex=3). A score >8 indicates a high risk of impending pathologic fracture, necessitating prophylactic internal fixation followed by local radiation.

Question 11

A 72-year-old man with known long-standing Paget's disease of the pelvis presents with a rapid increase in localized pain over the right ilium and a new palpable mass. Laboratory studies show a sudden exponential rise in serum alkaline phosphatase. What is the most likely diagnosis?

Explanation

Sarcomatous degeneration (usually into osteosarcoma) is a rare but highly lethal complication of Paget's disease, occurring in <1% of patients. It should be suspected when a patient with Paget's disease develops sudden worsening pain, a new mass, or an exponential rise in alkaline phosphatase.

Question 12

A 2-year-old boy presents with an anterolateral bowing of the tibia. Radiographs show medullary sclerosis and a narrow canal at the apex of the deformity.

What is the underlying genetic mutation most commonly associated with this specific condition?

Explanation

Anterolateral bowing of the tibia and subsequent congenital pseudarthrosis are highly associated with Neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant disorder caused by a mutation in the neurofibromin gene on chromosome 17.

Question 13

A 10-year-old girl with a known history of neurofibromatosis type 1 develops a rapidly progressive spinal deformity. Radiographs demonstrate a short-segment, sharp angular curve with vertebral scalloping and severe rib penciling.

What is the most appropriate definitive management for this deformity?

Explanation

Dystrophic scoliosis in NF1 is characterized by a short, sharp curve, rib penciling, and severe progression. Due to the exceptionally high risk of curve progression and pseudarthrosis, a combined anterior and posterior spinal fusion is typically required.

Question 14

A 30-year-old woman presents with knee pain. Radiographs show an eccentric, purely lytic epiphyseal lesion in the distal femur extending precisely to the subchondral bone plate. A biopsy reveals multinucleated giant cells within a stroma of mononuclear cells. Which targeted therapy is most appropriate for locally advanced, unresectable cases of this tumor?

Explanation

The diagnosis is a Giant Cell Tumor of bone. Denosumab, a monoclonal antibody against RANKL, prevents the maturation and activation of osteoclasts and the multinucleated giant cells, making it the primary medical treatment for unresectable cases.

Question 15

A 14-year-old boy presents with a painful, swollen thigh and low-grade fever. Radiographs show a permeative, diaphyseal lesion with an "onion-skin" periosteal reaction. Which chromosomal translocation is most characteristic of this malignancy?

Explanation

Ewing sarcoma typically presents in the diaphysis with a permeative pattern and "onion-skinning." It is classically associated with the t(11;22) translocation, which creates the EWS-FLI1 fusion oncogene.

Question 16

A 16-year-old girl has a destructive metaphyseal lesion in the proximal tibia accompanied by a "sunburst" periosteal reaction. A core needle biopsy confirms high-grade conventional osteosarcoma. Following neoadjuvant chemotherapy and surgical resection, what is the most critical prognostic factor for her long-term survival?

Explanation

The degree of tumor necrosis after neoadjuvant chemotherapy is the single most important prognostic factor for survival in osteosarcoma. Greater than 90% necrosis defines a good responder and portends a better prognosis.

Question 17

A 55-year-old man presents with progressive pain in his proximal humerus. Radiographs show a lytic lesion with intralesional "popcorn" calcifications and endosteal scalloping involving >2/3 of the cortical thickness. Biopsy confirms a grade 2 chondrosarcoma. What is the optimal initial treatment?

Explanation

Conventional intermediate to high-grade chondrosarcomas are notably resistant to both conventional chemotherapy and radiation. Wide surgical resection with negative margins remains the mainstay of curative treatment.

Question 18

A 65-year-old man presents with generalized back pain, fatigue, and hypercalcemia. A skeletal survey demonstrates multiple "punched-out" lytic lesions in the skull and spine. Serum protein electrophoresis reveals a monoclonal IgG spike. What specific cell type is primarily responsible for the bone resorption seen in this disease process?

Explanation

In multiple myeloma, the lytic bone lesions are caused by marked osteoclast activation, not direct destruction by tumor cells. Malignant plasma cells secrete factors (like RANKL and MIP-1a) that upregulate osteoclast activity while suppressing osteoblasts.

Question 19

A 12-year-old girl presents with pain and swelling of her distal femur. MRI reveals an expansile, multiloculated metaphyseal lesion containing multiple fluid-fluid levels. Genetic testing of the biopsy specimen identifies a rearrangement of the USP6 gene. What is the diagnosis?

Explanation

Primary aneurysmal bone cysts (ABCs) are characterized radiographically by fluid-fluid levels on MRI and genetically by translocations involving the USP6 gene on chromosome 17p13.

Question 20

A 19-year-old male complains of severe, unrelenting night pain in his proximal tibia, which is completely relieved within 30 minutes of taking ibuprofen. A high-resolution CT scan shows a 7 mm radiolucent nidus surrounded by intense reactive sclerosis. What is the pathophysiologic mechanism directly responsible for the pain?

Explanation

Osteoid osteomas produce exceptionally high levels of prostaglandins, specifically PGE2, which dramatically lowers the pain threshold. This mechanism explains the classic, dramatic relief of pain with NSAIDs.

Question 21

A 25-year-old man presents with a slow-growing, painful mass in the anterior mid-diaphysis of his tibia. Radiographs reveal a multilocular, eccentric "soap-bubble" lytic lesion. Histological analysis demonstrates a biphasic pattern consisting of an epithelial component embedded within a bland osteofibrous stroma. What is the diagnosis?

Explanation

Adamantinoma is a rare, low-grade malignant bone tumor that almost exclusively occurs in the tibial diaphysis. It is uniquely characterized by its biphasic histology, containing both epithelial (keratin-positive) and osteofibrous components.

Question 22

A 9-year-old girl is evaluated for precocious puberty, hyperpigmented cutaneous macules with irregular borders, and multiple expansile bone lesions exhibiting a "ground-glass" matrix on radiographs. This syndrome is caused by a somatic activating mutation in which of the following genes?

Explanation

The patient has McCune-Albright syndrome, characterized by polyostotic fibrous dysplasia, precocious puberty, and "coast of Maine" café-au-lait spots. It is caused by a somatic, post-zygotic activating mutation in the GNAS gene.

Question 23

A 60-year-old woman presents with a purely destructive lytic lesion in her proximal humerus. An image-guided biopsy shows clear cell morphology consistent with a metastatic carcinoma. Prior to proceeding with prophylactic internal fixation, what critical preoperative study must be obtained to prevent a catastrophic intraoperative complication?

Explanation

The scenario describes metastatic renal cell carcinoma (lytic lesion, clear cells). Renal and thyroid metastases are highly vascular; therefore, preoperative angiography and embolization are crucial to prevent massive intraoperative hemorrhage.

Question 24

A 55-year-old man presents with progressive bowel and bladder dysfunction. MRI reveals a large, destructive, midline sacral mass. Biopsy reveals cords of cells with bubbly, vacuolated cytoplasm that immunostain positive for brachyury. What is the embryological origin of this tumor?

Explanation

Chordomas are locally aggressive, low-grade malignant tumors that arise from the remnants of the embryonic notochord. They are uniquely defined histologically by physaliferous (bubbly) cells and immunohistochemically by brachyury expression.

Question 25

A 68-year-old man presents with an increasing hat size, unilateral hearing loss, and an anterolateral bowing deformity of his right femur. Radiographs show marked cortical thickening and coarse trabeculae. Which of the following laboratory profiles is most characteristic of this condition?

Explanation

Paget disease of bone features dramatically accelerated, disorganized bone turnover. Serum calcium and phosphate levels typically remain normal, while alkaline phosphatase (ALP) is markedly elevated due to intense osteoblastic compensation.

Question 26

An 8-year-old boy sustains a low-energy fracture of the proximal humerus. Radiographs show a centrally located, completely radiolucent metaphyseal lesion with a piece of cortical bone resting dependently at the bottom of the cyst cavity. What is this pathognomonic radiographic sign called?

Explanation

The "fallen leaf" or "fallen fragment" sign occurs when a piece of fractured cortex falls through the fluid-filled cavity to the dependent portion of the lesion. It is highly specific for a unicameral (simple) bone cyst.

Question 27

A 12-year-old girl is diagnosed with multiple enchondromatosis. Physical examination also reveals numerous soft tissue hemangiomas with visible phleboliths on extremity radiographs. Which syndrome does she have, and what is her lifetime risk of malignant transformation to chondrosarcoma?

Explanation

Maffucci syndrome is distinguished from Ollier disease by the concomitant presence of soft tissue hemangiomas. It carries an extremely high lifetime risk of malignant transformation to chondrosarcoma, approaching 100%.

Question 28

A 2-year-old boy with multiple cafe-au-lait spots presents with the severe lower extremity deformity shown in the clinical and radiographic context.

What is the underlying genetic mutation most commonly associated with this specific osseous manifestation?

Explanation

Congenital anterolateral bowing of the tibia and subsequent pseudarthrosis are hallmark orthopedic manifestations of Neurofibromatosis type 1 (NF1). NF1 is caused by a mutation in the neurofibromin gene on chromosome 17.

Question 29

A 14-year-old boy presents with a painful diaphyseal mass in the femur. Biopsy reveals uniform small round blue cells. Cytogenetic analysis identifies a t(11;22)(q24;q12) translocation. Which of the following fusion proteins is driving this pathology?

Explanation

Ewing sarcoma classically presents as a diaphyseal bone lesion in adolescents, histologically appearing as small round blue cells. The characteristic t(11;22) translocation results in the EWS-FLI1 fusion protein.

Question 30

A 65-year-old man presents with a painful proximal humerus mass. Radiographs show a destructive medullary lesion with intralesional "popcorn" calcifications and endosteal scalloping involving >2/3 of the cortical thickness. What is the most appropriate definitive management?

Explanation

This clinical and radiographic picture strongly suggests conventional chondrosarcoma. Wide surgical resection is the mainstay of treatment, as these tumors are generally resistant to both traditional chemotherapy and radiation.

Question 31

A 10-year-old girl with known Neurofibromatosis type 1 presents with a sharp, angular, short-segment thoracic scoliosis.

Which of the following features is highly indicative of a dystrophic curve that carries a high risk of rapid progression?

Explanation

Dystrophic scoliosis in NF1 is characterized by penciling of the ribs, severe apical vertebral wedging, dural ectasia, and enlarged neural foramina. These specific curves progress rapidly and typically require early surgical stabilization.

Question 32

A 32-year-old woman presents with knee pain. Radiographs reveal an eccentric, lytic, epiphyseal lesion in the proximal tibia extending to the subchondral bone. Biopsy shows multinucleated giant cells in a background of mononuclear stromal cells. Which targeted therapy is most appropriate if the lesion is deemed unresectable?

Explanation

Giant cell tumors of bone consist of neoplastic mononuclear stromal cells that express RANKL, which recruits reactive osteoclast-like giant cells causing osteolysis. Denosumab, a monoclonal RANKL inhibitor, is highly effective for downstaging or managing unresectable disease.

Question 33

A 16-year-old boy presents with severe nocturnal thigh pain that is completely relieved by ibuprofen. Imaging shows a 1 cm radiolucent nidus surrounded by dense reactive sclerosis in the femoral diaphysis. What is the primary mechanism of pain relief by NSAIDs in this condition?

Explanation

Osteoid osteomas characteristically produce high levels of prostaglandin E2 (PGE2) due to intense COX-2 expression within the nidus. NSAIDs relieve pain by directly inhibiting this COX-mediated PGE2 production.

Question 34

A 25-year-old patient presents with a "shepherd's crook" deformity of the proximal femur. Radiographs show an expansile lesion with a "ground-glass" appearance. A somatic activating mutation in which of the following genes is characteristic of this condition?

Explanation

Fibrous dysplasia is caused by a post-zygotic, somatic activating mutation in the GNAS gene. This leads to increased intracellular cAMP, which impairs the normal differentiation of bone-forming cells.

Question 35

A 70-year-old man presents with increasing hat size, hearing loss, and bowing of the tibiae. Laboratory tests show markedly elevated serum alkaline phosphatase but normal calcium and phosphorus levels. What is the primary cellular defect in the initial phase of this disease?

Explanation

Paget's disease initiates with a chaotic, intense osteoclastic resorption phase driven by abnormal, hypernucleated osteoclasts. This is subsequently followed by a rapid, disorganized osteoblastic response forming weak woven bone.

Question 36

A neonate sustains multiple fractures during birth. Examination reveals blue sclerae and bowing of the upper and lower extremities. The underlying genetic defect typically involves the substitution of which crucial amino acid in the collagen triple helix?

Explanation

Osteogenesis imperfecta (OI) is primarily caused by mutations in the COL1A1 or COL1A2 genes. These mutations typically lead to the substitution of glycine, the smallest amino acid essential for the tight coiling of the type I collagen triple helix.

Question 37

A 9-year-old boy presents with a pathologic fracture of the proximal humerus through a centrally located, completely lytic diaphyseal lesion demonstrating a "fallen leaf" sign on plain radiographs. What is the most appropriate initial management after the fracture has completely healed?

Explanation

The "fallen leaf" or "fallen fragment" sign is pathognomonic for a simple (unicameral) bone cyst. After the fracture heals (which occasionally obliterates the cyst), standard management involves observation or minimally invasive injections (corticosteroids or bone marrow aspirate) for persistent cysts.

Question 38

A 15-year-old girl presents with a rapidly expansile, eccentric lytic lesion in the distal femur. MRI reveals multiple fluid-fluid levels. Genetic analysis of the biopsy reveals a USP6 gene rearrangement. What is the optimal surgical treatment?

Explanation

Aneurysmal bone cysts (ABCs) carrying USP6 translocations are considered primary neoplastic lesions rather than purely reactive ones. Extended intralesional curettage using a high-speed burr, followed by local adjuvants and grafting/cementing, is the standard of care with low recurrence rates.

Question 39

A 65-year-old woman presents with severe, progressive back pain. Radiographs show multiple "punched-out" lytic lesions in the skull and vertebrae. Serum protein electrophoresis shows an M-spike. Which pathway is primarily responsible for the prominent osteolytic lesions seen in this condition?

Explanation

Multiple myeloma cells secrete factors (such as MIP-1 alpha and IL-6) that upregulate RANKL expression on osteoblasts and simultaneously downregulate OPG. This severe imbalance leads to massive osteoclast activation and characteristic lytic bone destruction.

Question 40

A 30-year-old man presents with a slow-growing, painful mass near the knee joint, distinct from the joint space. Imaging shows stippled calcifications within the soft tissue mass. Biopsy reveals a biphasic spindle cell pattern. Which chromosomal translocation is diagnostic for this tumor?

Explanation

Synovial sarcoma frequently occurs near large joints (but rarely inside the joint space) and is classically characterized by the t(X;18)(p11;q11) translocation. This chromosomal abnormality results in the SYT-SSX fusion gene.

Question 41

A 12-year-old boy undergoes a knee radiograph after an ankle sprain. An incidental eccentrically located, multi-loculated, radiolucent lesion with a sclerotic rim is seen in the distal femoral metaphysis, occupying less than 25% of the bone diameter. What is the most appropriate management?

Explanation

This classic presentation describes a non-ossifying fibroma (NOF), a common, benign, self-limiting fibro-osseous defect of childhood. Asymptomatic lesions that do not compromise structural integrity require only observation and reassurance, as they typically ossify by early adulthood.

Question 42

A 14-year-old boy with confirmed Neurofibromatosis Type 1 presents with severe neck pain and torticollis.

What is the most critical cervical spine pathology to screen for in this patient population?

Explanation

Patients with NF1 are prone to severe, progressive cervical kyphosis, which is often associated with dural ectasia and severe vertebral body wedging. This can lead to rapid neurologic deterioration and requires careful screening and potential early surgical stabilization.

Question 43

A 3-year-old boy presents with severe bowing of the legs and short stature. Labs show normal serum calcium, very low serum phosphorus, normal PTH, and elevated alkaline phosphatase. Genetic testing reveals a mutation in the PHEX gene. What is the core pathophysiology of this specific disease?

Explanation

X-linked hypophosphatemic rickets is caused by a PHEX mutation, which ultimately leads to the unregulated overproduction of FGF-23. Elevated FGF-23 strongly inhibits renal phosphate reabsorption, causing profound hypophosphatemia and defective bone mineralization.

Question 44

A 4-year-old child presents with anterior and lateral bowing of the tibia. Radiographs show a pseudarthrosis. Examination reveals axillary freckling and multiple hyperpigmented macules.

What is the genetic mutation associated with this condition?

Explanation

The patient has Neurofibromatosis type 1 (NF1), characterized by anterolateral tibial bowing and congenital pseudarthrosis. NF1 is caused by a mutation in the NF1 gene on chromosome 17, which encodes the tumor suppressor protein neurofibromin.

Question 45

A 14-year-old boy presents with a destructive metadiaphyseal lesion in the distal femur. Biopsy confirms high-grade osteosarcoma. Which of the following tumor suppressor genes are most commonly implicated in the pathogenesis of this tumor?

Explanation

Osteosarcoma is frequently associated with mutations in the TP53 (Li-Fraumeni syndrome) and RB1 (Retinoblastoma) tumor suppressor genes. These mutations lead to uncontrolled cell cycle progression and malignant transformation.

Question 46

A 10-year-old boy presents with a painful, swollen thigh and low-grade fever. Radiographs show a permeative diaphyseal lesion with an "onion-skin" periosteal reaction. Biopsy reveals small, round blue cells. Which chromosomal translocation is highly diagnostic?

Explanation

Ewing sarcoma is characterized by the t(11;22)(q24;q12) translocation, resulting in the EWSR1-FLI1 fusion protein. It typically presents as a permeative diaphyseal lesion in children.

Question 47

A 32-year-old woman presents with a lytic epiphyseal lesion of the proximal tibia. Biopsy confirms Giant Cell Tumor (GCT). For an unresectable lesion, which pharmacologic agent is most specifically targeted to the pathophysiology of this tumor?

Explanation

Denosumab is a monoclonal antibody against RANKL. It inhibits the recruitment and activation of osteoclast-like giant cells in GCT, causing ossification and tumor stabilization.

Question 48

A 12-year-old girl with known Neurofibromatosis type 1 presents with a rapidly progressive spinal deformity.

Radiographs show a short-segmented, sharp angular curve with vertebral scalloping and rib penciling. What is the most appropriate management?

Explanation

Dystrophic scoliosis in NF1 has a high risk of progression and pseudarthrosis. Bracing is ineffective, and robust combined anterior and posterior spinal fusion is often required to achieve stability and prevent curve progression.

Question 49

A 9-year-old boy sustains a minor mechanical fall and presents with arm pain. Radiographs reveal a pathologic fracture through a centrally located, lytic diaphyseal lesion of the proximal humerus with a "fallen leaf" sign. What is the most appropriate initial management?

Explanation

A unicameral bone cyst (UBC) presenting with a pathologic fracture is initially treated with immobilization to allow the fracture to heal. Surgery or injections are reserved for persistent cysts after the fracture has consolidated.

Question 50

A 12-year-old patient presents with multiple cafe-au-lait spots, axillary freckling, and Lisch nodules.

The genetic mutation responsible for this condition affects a protein that normally acts as a:

Explanation

Neurofibromatosis type 1 is caused by a mutation in the NF1 gene on chromosome 17, which encodes neurofibromin. Neurofibromin is a GTPase-activating protein (GAP) that normally downregulates Ras; its loss leads to uncontrolled cellular proliferation.

Question 51

A 3-year-old boy presents with marked anterolateral bowing of the tibia and an established pseudoarthrosis.

What is the most appropriate surgical treatment principle for managing this specific tibial pathology?

Explanation

Congenital pseudarthrosis of the tibia in NF1 is notoriously difficult to heal due to surrounding fibrous hamartoma. The gold standard surgical treatment involves aggressive resection of the hamartomatous tissue, autogenous bone grafting, and rigid intramedullary stabilization.

Question 52

A 15-year-old boy undergoes neoadjuvant chemotherapy followed by limb-salvage surgery for a high-grade, intramedullary osteosarcoma of the distal femur. What is the most important prognostic factor for his long-term survival?

Explanation

The most important prognostic factor for long-term survival in patients with high-grade osteosarcoma without metastases at presentation is the histological response to neoadjuvant chemotherapy. A favorable response is defined as greater than 90% tumor necrosis upon pathologic evaluation of the resected specimen.

Question 53

A 12-year-old girl presents with fever, elevated ESR, and a permeative diaphyseal lesion in her femur with 'onion skin' periosteal reaction. A biopsy is performed. Which chromosomal translocation is classically associated with her diagnosis?

Explanation

The patient's presentation and imaging are classic for Ewing sarcoma. This tumor is strongly associated with the t(11;22) translocation, which creates the EWS-FLI1 fusion protein that acts as an aberrant transcription factor driving oncogenesis.

Question 54

A 55-year-old male presents with a large pelvic mass. Biopsy demonstrates atypical chondrocytes with binucleation and myxoid stroma, consistent with a high-grade conventional chondrosarcoma. What is the most appropriate primary treatment modality?

Explanation

Conventional chondrosarcoma is notably resistant to both chemotherapy and radiation therapy. Therefore, the mainstay of definitive treatment is wide surgical resection with negative margins.

Question 55

A 30-year-old female presents with a destructive, eccentrically located epiphyseal lesion in the distal femur. Biopsy confirms a Giant Cell Tumor (GCT). If medical therapy with Denosumab is initiated, what is the specific cellular target of this drug?

Explanation

Denosumab is a monoclonal antibody that specifically binds to RANKL (Receptor Activator of Nuclear factor Kappa-B Ligand), which is secreted by the neoplastic mononuclear stromal cells in GCT. By neutralizing RANKL, it prevents the recruitment and activation of osteoclast-like giant cells.

Question 56

An 18-year-old male complains of severe nocturnal thigh pain that is completely relieved by ibuprofen. Radiographs show a 1.0 cm radiolucent nidus surrounded by dense reactive sclerosis in the femoral diaphysis. The intense pain is pathogenically caused by the secretion of which substance by the nidus?

Explanation

Osteoid osteomas secrete high levels of Prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) from the nidus. This causes intense local inflammation and nocturnal pain, explaining the dramatic symptomatic relief achieved with NSAIDs.

Question 57

A 65-year-old man presents with progressive bowing of his tibiae and an increasing hat size. Laboratory tests reveal an isolated, markedly elevated alkaline phosphatase. A bone biopsy during the late phase of this disease would most likely show:

Explanation

The patient has Paget's disease of bone. The histologic hallmark of the late (sclerotic/mixed) phase is a 'mosaic pattern' of lamellar bone with haphazard, prominent cement lines resulting from chaotic cycles of bone resorption and formation.

Question 58

Achondroplasia is the most common form of short-limb dwarfism. At the cellular level, the underlying genetic mutation results in which of the following mechanisms?

Explanation

Achondroplasia is caused by a gain-of-function mutation in the FGFR3 gene. This results in constitutive activation of the receptor, which paradoxically inhibits chondrocyte proliferation in the proliferative zone of the physis.

Question 59

A patient with end-stage renal disease (ESRD) presents with diffuse bone pain. Labs show hypocalcemia, hyperphosphatemia, and severely elevated Parathyroid Hormone (PTH) levels. The primary underlying defect causing impaired bone mineralization in this patient is a deficiency of:

Explanation

In renal osteodystrophy, the failing kidneys lose 1-alpha-hydroxylase activity, preventing the conversion of 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D. This leads to decreased intestinal calcium absorption, hypocalcemia, and severe secondary hyperparathyroidism.

Question 60

A 2-year-old boy presents with anterolateral bowing of the tibia and multiple café-au-lait macules. Radiographs demonstrate thinning of the tibial cortex and impending fracture.

What is the normal physiologic function of the protein encoded by the mutated gene responsible for this condition?

Explanation

Neurofibromatosis type 1 is caused by a mutation in the NF1 gene on chromosome 17, which encodes neurofibromin. Neurofibromin acts as a GTPase-activating protein that downregulates Ras signaling; its absence leads to hyperactive Ras and subsequent tissue dysplasia.

Question 61

A 32-year-old woman presents with a lytic lesion in the distal femur extending into the subchondral bone. Biopsy confirms a Giant Cell Tumor of bone. She is treated with denosumab preoperatively to consolidate the tumor margins. What is the exact mechanism of action of this medication?

Explanation

Denosumab is a monoclonal antibody that targets and binds to RANKL, preventing it from binding to the RANK receptor on osteoclasts. This effectively inhibits osteoclast differentiation and function, targeting the reactive multinucleated giant cells characteristic of the tumor.

Question 62

A 55-year-old man undergoes wide resection of a large, painful cartilaginous tumor of the proximal humerus. Histopathology reveals a conventional grade II chondrosarcoma. Which of the following metabolic gene mutations is most frequently implicated in the pathogenesis of this specific tumor?

Explanation

Mutations in Isocitrate Dehydrogenase 1 or 2 (IDH1/IDH2) are found in up to 50-60% of central conventional chondrosarcomas. These mutations alter cellular metabolism, leading to the pathologic accumulation of the oncometabolite D-2-hydroxyglutarate.

Question 63

A 10-year-old girl is evaluated for a severe shepherd's crook deformity of the proximal femur and precocious puberty. Radiographs show extensive 'ground-glass' opacities in the affected bone. The pathogenesis of her underlying musculoskeletal condition is directly related to which of the following molecular mechanisms?

Explanation

The patient has McCune-Albright syndrome, which includes polyostotic fibrous dysplasia. This is caused by an activating post-zygotic somatic mutation in the GNAS gene, leading to constitutive activation of adenylyl cyclase and elevated intracellular cAMP.

Question 64

A 14-year-old boy complains of intense thigh pain that worsens at night and is dramatically relieved by ibuprofen. Imaging reveals a 1 cm radiolucent nidus surrounded by dense sclerotic bone in the proximal femur. Which of the following biochemical mediators is secreted in excess by the central nidus?

Explanation

Osteoid osteomas typically produce high levels of Prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) within the central nidus. This robust production accounts for the profound localized pain that is classically responsive to NSAIDs.

Question 65

A 28-year-old man presents with a slow-growing, painful mass near his knee joint. MRI shows a well-circumscribed, lobulated mass in the popliteal fossa with calcifications. Biopsy reveals a biphasic proliferation of spindle cells and epithelial cells. Which chromosomal translocation is highly diagnostic for this tumor?

Explanation

Synovial sarcoma is characterized by the t(X;18) translocation, resulting in the SS18-SSX fusion gene. The other translocations represent Ewing sarcoma t(11;22), extraskeletal myxoid chondrosarcoma t(9;22), myxoid liposarcoma t(12;16), and alveolar rhabdomyosarcoma t(2;13).

Question 66

An 8-year-old girl is found to have an expansile, eccentric lytic lesion in the metaphysis of her distal radius. MRI demonstrates multiple fluid-fluid levels within the lesion. Genetic analysis of the primary lesion would most likely reveal a translocation leading to the upregulation of which of the following genes?

Explanation

Primary aneurysmal bone cysts (ABCs) are neoplastic and driven by translocations resulting in the upregulation of the USP6 gene. This specific genetic marker distinguishes primary ABCs from secondary ABC-like changes found in other bone tumors.

Question 67

A 62-year-old man with a history of nephrectomy for renal cell carcinoma presents with a solitary lytic metastasis in the proximal femur causing an impending pathologic fracture. Prior to prophylactic internal stabilization, which adjunctive intervention is most critical to minimize perioperative surgical morbidity?

Explanation

Metastases from renal cell carcinoma and thyroid carcinoma are notoriously hypervascular. Preoperative selective arterial embolization 24-48 hours before surgical stabilization is strongly recommended to minimize massive, potentially life-threatening intraoperative blood loss.

Question 68

An infant presents with recurrent fractures, cranial nerve palsies, and diffuse uniform osteosclerosis on whole-body radiographs. Bone marrow aspiration is dry, and a diagnosis of infantile malignant osteopetrosis is suspected. What is the primary cellular defect in this disorder?

Explanation

Osteopetrosis is characterized by the failure of osteoclasts to resorb bone due to defects in maintaining an acidic environment (e.g., CAII or TCIRG1 mutations) or defective ruffled border formation. This failure of bone turnover leads to overly dense, brittle bone and subsequent marrow obliteration.

Question 69

A 35-year-old woman presents with a slow-growing mass on the anterior aspect of her tibia. Radiographs show a distinct eccentric 'soap bubble' lytic lesion in the anterior tibial diaphysis. Histology reveals biphasic nests of epithelial cells surrounded by a bland fibrous stroma. Which immunohistochemical marker will predictably be strongly positive in the epithelial component?

Explanation

Adamantinoma is a rare, low-grade malignant bone tumor that classically presents in the anterior tibial diaphysis. It is characterized by its biphasic histology, containing epithelial cells that stain strongly positive for cytokeratin, distinguishing it from fibrous dysplasia or osteofibrous dysplasia.

Question 70

A 14-year-old girl with a known genetic disorder presents for evaluation of progressive back pain and clinical deformity.

Given her underlying diagnosis of Neurofibromatosis Type 1, what is the most typical characteristic of the dystrophic spinal deformity frequently seen in these patients?

Explanation

Dystrophic scoliosis in Neurofibromatosis Type 1 classically presents as a short, sharply angulated curve typically involving 4-6 vertebrae. It is highly associated with structural anomalies such as dural ectasia, severely thinned pedicles, and posterior vertebral body scalloping.

Question 71

A 70-year-old man presents with increasing hat size, sensorineural hearing loss, and a significant bowing deformity of his right femur. Laboratory evaluation shows an isolated marked elevation of serum alkaline phosphatase. The initial pathogenic phase of this disease process is driven primarily by which of the following?

Explanation

Paget disease of bone begins with an initial, intensely osteoclastic (lytic) phase characterized by massive localized bone resorption. This is followed sequentially by a mixed osteoclastic/osteoblastic phase, and finally an inactive osteosclerotic phase.

Question 72

A 9-year-old boy sustains a minor fall and presents with arm pain. X-rays reveal a central, purely lytic lesion in the proximal humerus displaying a classic 'fallen leaf' sign. Aspiration of the lesion yields clear serous fluid. What is the most appropriate initial management for this presentation?

Explanation

The presentation and the 'fallen leaf' sign are pathognomonic for a Unicameral Bone Cyst (UBC) complicated by a pathologic fracture. Initial management of a fractured UBC is typically immobilization to allow the fracture to heal, which occasionally promotes simultaneous spontaneous healing of the cyst.

Question 73

A 12-year-old boy with a family history of multiple palpable bone bumps presents with a new, rapidly enlarging, painful mass on his distal femur. Radiographs reveal multiple sessile and pedunculated osteocartilaginous lesions pointing away from the joint spaces. What gene mutation is most likely responsible for his underlying baseline condition?

Explanation

Multiple Hereditary Exostoses (MHE) is an autosomal dominant disorder caused by loss-of-function mutations in the EXT1 or EXT2 genes. These genes synthesize heparan sulfate, and their impairment disrupts normal physeal signaling, leading to multiple osteochondromas.

Question 74

A 14-year-old boy presents with chronic knee pain. Radiographs reveal a 2 cm eccentric, purely lytic lesion located entirely within the distal femoral epiphysis. Biopsy demonstrates mononuclear cells and areas of chondroid matrix with fine, 'chicken-wire' calcifications. Which of the following genetic mutations is most strongly associated with this lesion?

Explanation

This presentation is classic for a chondroblastoma, an epiphyseal lesion typically seen in growing children. It is characterized by H3F3B mutations, whereas H3F3A mutations are characteristically seen in Giant Cell Tumor of bone.

Question 75

An 8-year-old boy presents with severe, progressive thoracic scoliosis. Physical examination reveals 7 cafe-au-lait spots measuring >5 mm and axillary freckling. Radiographs demonstrate a sharp, short-segment angular kyphoscoliosis.

What is the primary cellular function of the protein encoded by the mutated gene in this condition?

Explanation

Neurofibromatosis Type 1 is caused by a mutation in the NF1 gene, which produces neurofibromin. Neurofibromin is a GTPase-activating protein (GAP) that normally downregulates the Ras signaling pathway.

Question 76

A 25-year-old woman presents with progressive right hip pain and a noticeable limp. Radiographs demonstrate a 'shepherd's crook' deformity of the proximal femur with a hazy, ground-glass matrix in the medullary canal. Which of the following underlying molecular defects is responsible for this condition?

Explanation

Fibrous dysplasia is caused by a post-zygotic, activating mutation in the GNAS gene. This leads to constitutive activation of adenylyl cyclase and increased intracellular cAMP, resulting in abnormal proliferation of fibrous tissue in bone.

Question 77

A 60-year-old man presents with a destructive lytic lesion in his humeral diaphysis. Biopsy reveals nests of clear cells with abundant cytoplasm. He has a known history of radical nephrectomy. What is the most appropriate next step prior to prophylactic surgical fixation of the humerus?

Explanation

Metastatic renal cell carcinoma and thyroid carcinoma lesions are notoriously hypervascular. Pre-operative angiographic embolization is highly recommended 24-48 hours before surgical stabilization to minimize massive intraoperative blood loss.

Question 78

A 16-year-old boy presents with a rapidly expanding, painful lytic lesion in the proximal humerus. MRI demonstrates a multiloculated lesion with prominent fluid-fluid levels. Biopsy confirms a primary aneurysmal bone cyst (ABC). Which genetic abnormality is the primary driver of this true neoplasm?

Explanation

Primary Aneurysmal Bone Cysts are now recognized as true neoplasms driven by USP6 gene rearrangements, most commonly t(16;17). Secondary ABCs, which lack this mutation, can arise in conjunction with other tumors like giant cell tumors or chondroblastomas.

Question 79

A 10-year-old boy presents with severe night pain in his anterior tibia that is dramatically relieved by ibuprofen. Radiographs show profound cortical sclerosis surrounding a 1 cm radiolucent nidus. The intense pain experienced by this patient is primarily mediated by high local concentrations of which of the following?

Explanation

Osteoid osteoma niduses synthesize abnormally high levels of cyclooxygenase-2 (COX-2) and prostaglandins, particularly PGE2. This local biochemical environment causes the classic nocturnal pain that is exquisitely sensitive to NSAIDs.

Question 80

A 32-year-old woman presents with knee pain. Radiographs reveal an eccentric, lytic lesion in the proximal tibia that extends to the subchondral bone. Biopsy demonstrates sheets of mononuclear stromal cells and numerous multinucleated giant cells. Which of the following best describes the mechanism of the targeted medical therapy for this condition?

Explanation

Giant Cell Tumor of bone consists of neoplastic mononuclear stromal cells that express RANKL, which recruits reactive, bone-destroying multinucleated giant cells. Denosumab is a monoclonal antibody that binds RANKL, effectively halting osteoclastogenesis and tumor-associated osteolysis.

Question 81

A 25-year-old man presents with a slowly enlarging, painful mass near his knee joint. Radiographs show a soft tissue mass with stippled calcifications. Biopsy demonstrates a biphasic tumor with both spindle cells and epithelial-like cells. Which of the following chromosomal translocations is characteristic of this malignancy?

Explanation

Synovial sarcoma is characterized by the t(X;18) translocation, resulting in the SYT-SSX fusion gene. Despite its name, it rarely arises directly from the synovium, though it commonly presents near large joints and frequently exhibits calcifications on imaging.

Question 82

A 65-year-old man presents with severe back pain, anemia, and hypercalcemia. Radiographs show multiple punched-out lytic skull lesions. A Technetium-99m bone scan is performed but fails to demonstrate increased uptake in the areas of destruction. What is the primary reason for this false-negative bone scan?

Explanation

Multiple myeloma lesions are classically 'cold' on technetium-99m bone scans because the malignant plasma cells secrete factors (like DKK1) that suppress osteoblastic activity. A skeletal survey or whole-body low-dose CT is required for accurate staging.

Question 83

A 70-year-old man complains of progressive bowing of his femurs, increasing hat size, and new-onset hearing loss. Labs show a markedly elevated alkaline phosphatase but normal serum calcium and phosphate. A biopsy of the affected bone would most likely demonstrate which of the following?

Explanation

Paget's disease of bone is characterized by excessive, uncoordinated osteoclastic and osteoblastic activity. This disordered remodeling results in thickened, mechanically weak bone with a pathognomonic 'mosaic' or 'jigsaw puzzle' pattern of cement lines on histology.

Question 84

A 28-year-old woman presents with a painless mass on the posterior aspect of her distal femur. Radiographs demonstrate a dense, lobulated, broad-based ossifying mass on the cortical surface with a 'string sign' separating part of the tumor from the cortex. There is no medullary involvement. Which genetic alteration is characteristic of this lesion?

Explanation

Parosteal osteosarcoma is a low-grade surface osteosarcoma classically located on the posterior aspect of the distal femur. It is cytogenetically characterized by supernumerary ring chromosomes containing MDM2 and CDK4 gene amplifications.

Question 85

A 4-year-old boy has a history of multiple fractures, hepatosplenomegaly, and severe anemia. Radiographs demonstrate generalized, extreme bone density with a 'bone-within-bone' appearance. What is the fundamental cellular defect in this condition?

Explanation

Osteopetrosis (Albers-Schönberg disease) results from defective osteoclastic bone resorption, frequently due to mutations in TCIRG1 or CLCN7. The osteoclasts lack the ruffled border necessary to secrete protons and acidify the resorption pit, leading to dense but extremely brittle bones.

Question 86

A 55-year-old man presents with deep thigh pain. Radiographs reveal a 6 cm lytic lesion in the proximal femur with 'ring and arc' calcifications and endosteal scalloping. Biopsy confirms a grade II (intermediate) chondrosarcoma. What is the most appropriate definitive management?

Explanation

Conventional chondrosarcomas are generally highly resistant to both chemotherapy and radiation therapy. Wide surgical resection with negative margins is the mainstay of treatment for intermediate (grade II) and high-grade (grade III) lesions.

Question 87

A 30-year-old man presents with a swelling on his lower leg. Radiographs reveal an eccentric, multilobulated lytic lesion in the anterior diaphyseal cortex of the tibia. Histologic evaluation shows nests of epithelial cells within a benign fibrous stroma. Which of the following is the most likely diagnosis?

Explanation

Adamantinoma is a rare, low-grade malignant bone tumor that occurs almost exclusively in the anterior diaphyseal cortex of the tibia. It is unique among primary bone tumors for its biphasic histology, containing epithelial cells that stain positive for cytokeratin.

Question 88

A 6-year-old girl is evaluated for an anterolateral bowing deformity of the tibia. Physical exam reveals axillary freckling and multiple Lisch nodules.

According to the NIH diagnostic criteria for this condition, which of the following additional findings would independently satisfy a diagnostic criterion?

Explanation

The diagnosis of Neurofibromatosis Type 1 requires 2 or more clinical criteria. An optic glioma is one of the major criteria. The criteria require at least 6 café-au-lait spots, at least 2 neurofibromas (or 1 plexiform), and a positive family history must be in a first-degree relative.

Question 89

A 9-year-old boy presents with mild shoulder pain after throwing a baseball. Radiographs reveal a centrally located, purely lytic lesion in the proximal humeral metaphysis. A small cortical fragment is seen resting at the dependent portion of the radiolucent cavity. What is the most likely diagnosis?

Explanation

The 'fallen leaf' or 'fallen fragment' sign on a radiograph represents a piece of fractured cortex resting at the bottom of a fluid-filled cavity. This sign is highly specific for a Unicameral (Simple) Bone Cyst complicated by a pathologic fracture.

Question 90

A 32-year-old woman presents with progressive knee pain. Radiographs reveal an eccentric, expansile, lytic lesion in the epiphysis of the distal femur that extends to the subchondral bone without a sclerotic margin. A core needle biopsy reveals a proliferation of uniform mononuclear cells interspersed with numerous multinucleated giant cells. Which of the following best describes the underlying cellular pathogenesis and the precise mechanism of targeted medical therapy for this condition?

Explanation

In giant cell tumor (GCT) of bone, the mononuclear spindle-like stromal cells are the true neoplastic component and they heavily express RANKL. This RANKL recruits and activates benign, osteoclast-like multinucleated giant cells (which express RANK) to cause bone resorption; denosumab is a monoclonal antibody that binds RANKL to halt this destructive process.

Orthopaedic Surgery Board Exam Review: ABOS Part I & AAOS OITE Prep Questions | Part 22210

ABOS Orthopedic Pathology & Bone Disease Board Review MCQs | Part 1

Key Takeaway

ABOS Orthopedic Pathology & Bone Disease Board Review MCQs | Part 1

Chapter Index