ABOS Board Review: Bone Tumors & Skeletal Dysplasias

Question 1

Achondroplasia is the most common form of short-limbed dwarfism. The underlying genetic defect is a gain-of-function mutation in the FGFR3 gene. Which zone of the physis is primarily affected by this mutation?

Explanation

Achondroplasia is caused by an activating mutation in FGFR3, which inhibits chondrocyte proliferation. This directly affects the proliferative zone of the physis, leading to impaired endochondral ossification.

Question 2

A 45-year-old male presents with persistent thigh pain. Radiographs show a permeative, destructive diaphyseal lesion with minimal periosteal reaction. Biopsy reveals sheets of uniform round blue cells. Immunohistochemistry is strongly positive for CD20 and CD45. What is the most appropriate initial management?

Explanation

Primary bone lymphoma (diffuse large B-cell) typically presents as a permeative lesion in adults. It is highly chemo- and radiosensitive, making systemic chemotherapy combined with radiation the primary treatment. Surgery is generally reserved for impending or actual fractures.

Question 3

A 30-year-old female presents with multiple cartilaginous lesions in the phalanges and multiple soft tissue hemangiomas. Which of the following gene mutations is most strongly associated with this syndrome?

Explanation

This presentation describes Maffucci syndrome, characterized by multiple enchondromas and soft tissue hemangiomas. Both Ollier disease and Maffucci syndrome are strongly linked to somatic mosaic mutations in the IDH1 or IDH2 genes.

Question 4

A newborn is diagnosed with a skeletal dysplasia characterized by rhizomelic shortening, frontal bossing, and midface hypoplasia. Radiographs show narrowing of the interpedicular distances in the lumbar spine. What is the inheritance pattern and associated gene mutation?

Explanation

Achondroplasia is the most common form of short-limb dwarfism, inherited in an autosomal dominant pattern. It is caused by an activating mutation in the FGFR3 gene, with approximately 80% of cases representing new spontaneous mutations.

Question 5

A 32-year-old female presents with a purely lytic, eccentric lesion in the distal femur extending to the subchondral bone. Biopsy confirms giant cell tumor of bone. Neoadjuvant therapy with denosumab is considered. What is the mechanism of action of this drug?

Explanation

Denosumab is a human monoclonal antibody that binds to RANKL, preventing it from activating RANK on the surface of osteoclasts and their precursors. In giant cell tumors, it halts the tumor-induced osteolysis mediated by the reactive giant cells.

Question 6

A 45-year-old male with achondroplasia presents with progressive neurogenic claudication. The most common cause of lumbar spinal stenosis in this patient population is:

Explanation

Achondroplasia features impaired endochondral ossification leading to congenitally short pedicles and progressively narrowing interpedicular distances from L1 to L5. This distinct anatomical variance is the primary structural cause of severe spinal stenosis in these patients.

Question 7

A 50-year-old male with Ollier disease presents with new-onset, progressive pain in his proximal humerus over the last 3 months. Radiographs demonstrate a pre-existing cartilaginous lesion now showing endosteal scalloping > 2/3 of cortical thickness and a new soft tissue mass. What is the most likely diagnosis?

Explanation

Patients with Ollier disease have a high risk (up to 30%) of malignant transformation into secondary chondrosarcoma. Pain, deep endosteal scalloping, cortical destruction, and soft tissue extension are classic signs of this malignant degeneration.

Question 8

An infant presents with short limbs and frontal bossing. Radiographs show narrowing of interpedicular distances from L1 to L5.

What is the primary cellular mechanism affected by the genetic mutation in this condition?

Explanation

Achondroplasia is caused by a gain-of-function mutation in FGFR3. This results in the suppression of chondrocyte proliferation within the proliferative zone of the physis, leading to rhizomelic dwarfism.

Question 9

A 32-year-old male presents with knee pain. Radiographs reveal an eccentric, lytic epiphyseal lesion in the distal femur. Biopsy reveals multinucleated giant cells and mononuclear stromal cells.

Which cell population harbors the neoplastic mutation, and what marker do they overexpress?

Explanation

In Giant Cell Tumor of bone, the mononuclear spindle-like stromal cells are the true neoplastic cells. They express RANKL, which recruits and stimulates normal osteoclast precursors to form the reactive multinucleated giant cells.

Question 10

A 65-year-old male presents with thigh pain. Radiographs show a permeative lytic lesion in the femoral diaphysis. MRI demonstrates a massive soft tissue mass, yet the cortical bone appears structurally intact on CT. Biopsy confirms primary bone lymphoma.

What is the most appropriate initial management for this lesion assuming no impending fracture?

Explanation

Primary bone lymphoma typically presents with a permeative lesion and large soft tissue mass but little cortical destruction. The mainstay of treatment is systemic chemotherapy (usually R-CHOP) combined with localized radiation therapy, avoiding surgery unless needed for fracture stabilization.

Question 11

Which of the following skeletal dysplasias is characterized by a mutation in the RUNX2 (CBFA1) gene, delayed closure of cranial sutures, and supernumerary teeth?

Explanation

Cleidocranial dysplasia is an autosomal dominant condition caused by a RUNX2 mutation, leading to defective intramembranous ossification. Hallmarks include absent or hypoplastic clavicles, delayed cranial suture closure, and supernumerary teeth.

Question 12

A 45-year-old female is diagnosed with multiple enchondromas predominantly affecting her right arm and leg, as well as multiple soft-tissue hemangiomas.

Which of the following statements is true regarding her condition?

Explanation

Maffucci syndrome presents with multiple enchondromatosis and soft-tissue hemangiomas. It is associated with a nearly 100% lifetime risk of malignant transformation, including chondrosarcoma and visceral or brain malignancies.

Question 13

A 4-year-old boy presents with short trunk dwarfism, prominent joints, myopia, and coxa vara. Cervical spine radiographs demonstrate odontoid hypoplasia. What is the genetic basis of this disorder?

Explanation

Spondyloepiphyseal dysplasia congenita (SEDc) is caused by a mutation in COL2A1 (Type II collagen). It is characterized by short-trunk dwarfism, atlantoaxial instability (odontoid hypoplasia), coxa vara, and myopia.

Question 14

An asymptomatic 30-year-old woman undergoes hand radiography following minor trauma, revealing a well-circumscribed, 1 cm central lytic lesion with stippled calcifications in the proximal phalanx.

There is no cortical breakthrough. What is the most appropriate management?

Explanation

The classic radiographic appearance of an asymptomatic enchondroma in the hand requires only observation. Surgical intervention (curettage) is reserved for symptomatic lesions, impending fractures, or documented rapid enlargement.

Question 15

A patient with achondroplasia

requires spinal surgery for severe neurogenic claudication. What anatomical feature of the lumbar spine primarily contributes to this stenosis?

Explanation

Achondroplasia is characterized by congenitally short pedicles and a progressive decrease in the interpedicular distance from L1 to L5. This anatomical anomaly strongly predisposes these patients to severe, multi-level spinal stenosis.

Question 16

A newborn is diagnosed with achondroplasia. Which of the following accurately describes the molecular pathophysiology of this skeletal dysplasia?

Explanation

Achondroplasia is caused by a gain-of-function mutation in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene. This mutation constitutively activates the receptor, leading to the abnormal inhibition of chondrocyte proliferation in the proliferative zone of the physis.

Question 17

A 32-year-old woman presents with knee pain. Radiographs show an eccentric, lytic epiphyseal-metaphyseal lesion of the distal femur. Biopsy confirms a Giant Cell Tumor. If she is treated with denosumab preoperatively, which histological change is most expected?

Explanation

Denosumab is a monoclonal antibody against RANKL. It prevents the RANK-RANKL interaction, leading to the rapid depletion of the reactive multinucleated giant cells and promotion of woven bone formation, while the underlying neoplastic mononuclear stromal cells persist.

Question 18

A 65-year-old man presents with thigh pain. Radiographs reveal a permeative, moth-eaten diaphyseal lesion in the femur with minimal periosteal reaction. Biopsy shows small, round blue cells that stain positive for CD45 and CD20. What is the most appropriate primary treatment for an uncomplicated presentation of this disease?

Explanation

The diagnosis is primary bone lymphoma (typically diffuse large B-cell). The standard of care is systemic multi-agent chemotherapy (such as CHOP-R) combined with local radiation therapy; surgery is reserved strictly for impending or actual pathologic fractures.

Question 19

A 28-year-old man sustains a minor trauma to his right ring finger and develops acute pain. Radiographs demonstrate a centrally located lytic lesion in the proximal phalanx with a pathologic fracture. What is the most appropriate management after the fracture heals?

Explanation

The presentation is classic for an enchondroma, which is the most common primary bone tumor of the hand. While asymptomatic lesions can be observed, symptomatic lesions or those with a healed pathologic fracture are typically treated with intralesional curettage and bone grafting.

Question 20

A 15-year-old girl presents with multiple asymmetric cartilaginous lesions in the appendicular skeleton and bluish, compressible subcutaneous nodules on her extremities. Which of the following is true regarding her condition?

Explanation

The patient has Maffucci syndrome, distinguished from Ollier disease by the presence of soft tissue hemangiomas. Unlike Ollier disease (which carries a 25-30% malignancy risk), the risk of malignant transformation in Maffucci syndrome approaches 100% over the patient's lifetime.

Question 21

Parents of a 6-month-old infant with achondroplasia report that the child has episodes of sleep apnea, snoring, and difficulty feeding. Neurological exam reveals hyperreflexia in the lower extremities. What is the most critical next step in management?

Explanation

Infants with achondroplasia are at high risk for foramen magnum stenosis, which can present with sleep apnea, hyperreflexia, and hypotonia. Urgent evaluation with an MRI of the craniocervical junction is required to assess for cord compression, which may necessitate surgical decompression to prevent sudden death.

Question 22

In a Giant Cell Tumor of bone, which specific cell population harbors the pathognomonic H3F3A mutation and is considered the true neoplastic component?

Explanation

The mononuclear spindle-shaped stromal cells are the true neoplastic cells in a Giant Cell Tumor of bone and typically harbor a mutation in the H3F3A gene. These cells secrete RANKL, which subsequently recruits and activates the non-neoplastic, reactive multinucleated giant cells.

Question 23

A skeletal survey of a child with achondroplasia will typically demonstrate which of the following pathognomonic pelvic radiographic findings?

Explanation

Achondroplasia classically presents with a 'champagne glass' pelvic cavity, which is wider than it is deep. Additional defining radiographic findings include squared, abbreviated iliac wings, horizontal acetabular roofs, and narrow greater sciatic notches.

Question 24

A 4-year-old child with disproportionate short stature is diagnosed with achondroplasia. What is the underlying genetic mutation and its typical inheritance pattern?

Explanation

Achondroplasia is caused by a gain-of-function mutation in the FGFR3 gene, inherited in an autosomal dominant pattern. Approximately 80% of cases are due to de novo mutations associated with advanced paternal age.

Question 25

A 3-year-old child with achondroplasia presents with delayed motor milestones, hypotonia, and signs of central sleep apnea.

Which of the following is the most appropriate initial diagnostic imaging modality?

Explanation

Foramen magnum stenosis is a critical and potentially lethal complication in young children with achondroplasia, leading to cervicomedullary compression and central sleep apnea. MRI of the craniocervical junction is the gold standard imaging modality to evaluate this.

Question 26

A 32-year-old female presents with progressive knee pain. Radiographs demonstrate an eccentric, lytic, epiphyseal-metaphyseal lesion of the distal femur extending to the subchondral bone.

Biopsy confirms a Giant Cell Tumor of bone. Which cell type is considered the primary neoplastic cell in this lesion?

Explanation

The neoplastic cells in a Giant Cell Tumor of bone are the mononuclear stromal (spindle) cells, which express RANKL. The characteristic multinucleated giant cells are merely reactive osteoclast-like cells recruited by the stromal cells.

Question 27

In the management of a massive, unresectable recurrent giant cell tumor of the sacrum, which of the following targeted medical therapies is the most appropriate primary treatment?

Explanation

Denosumab is a monoclonal antibody against RANKL, which is overexpressed by the neoplastic mononuclear stromal cells in GCT. It effectively inhibits the recruitment and function of reactive osteoclast-like giant cells, making it the treatment of choice for unresectable cases.

Question 28

A 65-year-old male presents with severe, unremitting thigh pain. Radiographs demonstrate a permeative, moth-eaten diaphyseal lesion in the femur with minimal periosteal reaction.

Biopsy reveals sheets of small round blue cells that stain positive for CD20. What is the most likely diagnosis?

Explanation

Primary bone lymphoma typically presents in older adults with a destructive, permeative lesion and remarkably minimal periosteal reaction. Positivity for CD20 confirms a B-cell lineage, distinguishing it from Ewing sarcoma and myeloma.

Question 29

A 45-year-old asymptomatic male is found to have an incidental well-defined medullary lesion in the proximal humerus with stippled "arcs and rings" calcifications.

Which MRI finding most strongly suggests transformation to a low-grade chondrosarcoma rather than a benign enchondroma?

Explanation

Features distinguishing low-grade chondrosarcoma from enchondroma include deep endosteal scalloping (greater than 2/3 of cortical thickness), cortical breakthrough, and soft tissue extension. Bone marrow edema can occasionally be seen in benign enchondromas, making deep scalloping a more reliable indicator.

Question 30

A 12-year-old boy presents with multiple unilateral enchondromas causing limb-length discrepancy and angular deformity.

Physical examination reveals no cutaneous or soft tissue hemangiomas. What is the diagnosis, and what is the estimated lifetime risk of malignant transformation?

Explanation

Ollier disease is characterized by multiple enchondromas, often with a unilateral predominance, without soft tissue hemangiomas (which would define Maffucci syndrome). The risk of malignant transformation to secondary chondrosarcoma in Ollier disease is roughly 25-30%.

Question 31

An adult male with achondroplasia presents with bilateral leg heaviness, weakness, and progressive neurogenic claudication.

What is the primary anatomical etiology of his spinal stenosis?

Explanation

Achondroplasia features a defect in endochondral ossification, leading to congenitally shortened pedicles and a narrowed spinal canal with a decreased interpedicular distance caudally. This predisposes these patients to severe, early-onset lumbar spinal stenosis.

Question 32

A 28-year-old patient undergoes extended intralesional curettage for a Campanacci Grade II giant cell tumor of the proximal tibia.

Which of the following surgical adjuncts is most commonly utilized to decrease the rate of local recurrence?

Explanation

The standard surgical treatment for most GCTs is extended intralesional curettage using a high-speed burr to remove macroscopic tumor. This is typically followed by local adjuvants like phenol, liquid nitrogen, or argon beam coagulation to eradicate residual microscopic disease.

Question 33

A 50-year-old female is diagnosed with primary diffuse large B-cell lymphoma of the right humerus. There is no impending or actual pathologic fracture.

What is the mainstay of treatment for this condition?

Explanation

Primary bone lymphoma is highly chemo- and radiosensitive. The standard treatment is systemic chemotherapy (e.g., R-CHOP for B-cell lymphoma) often combined with localized radiation therapy; prophylactic surgical stabilization is reserved only for impending or actual pathologic fractures.

Question 34

Which of the following structural defects is primarily responsible for the clinical manifestations seen in patients with Osteogenesis Imperfecta?

Explanation

Osteogenesis imperfecta is most commonly caused by mutations in the COL1A1 or COL1A2 genes. This leads to quantitative or qualitative defects in Type I collagen, which is the major structural protein in bone, sclera, and dentin.

Question 35

A 5-year-old child presents with disproportionate short stature, normal facies, and marked joint laxity. Radiographs demonstrate delayed epiphyseal ossification and irregular metaphyses. Genetic testing reveals a mutation in the COMP (Cartilage Oligomeric Matrix Protein) gene. What is the most likely diagnosis?

Explanation

Pseudoachondroplasia is an autosomal dominant disorder caused by mutations in the COMP gene. Unlike true achondroplasia, patients have normal facial features and head circumference at birth, with growth failure and joint laxity becoming apparent in early childhood.

Question 36

A 35-year-old male with a history of a distal radius giant cell tumor presents 2 years post-resection. Routine chest imaging reveals multiple small pulmonary nodules. Biopsy of a nodule confirms benign GCT histology. What is this phenomenon called, and what is its typical clinical behavior?

Explanation

Giant Cell Tumors of bone can undergo "benign pulmonary metastasis" in 2-4% of cases. Despite the metastatic spread to the lungs, the lesions retain benign histology and often have an indolent clinical course, and can be managed with observation or surgical resection.

Question 37

A 32-year-old female presents with an incidental finding on a hand radiograph taken after mild trauma. The image shows a well-defined lucency with stippled calcification in the proximal phalanx, with no cortical breakthrough or soft tissue mass. What is the most appropriate next step in management?

Explanation

This is a classic presentation of an asymptomatic enchondroma of the hand. In the absence of pathologic fracture or significant pain, observation and reassurance is the standard of care.

Question 38

A 28-year-old female presents with knee pain. Radiographs show an eccentric, lytic epiphyseal lesion extending to the subchondral bone. Biopsy confirms a tumor characterized by mononuclear stromal cells and 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 is driven by RANKL-expressing neoplastic stromal cells that recruit osteoclast-like giant cells. Denosumab, a monoclonal antibody that inhibits RANKL, is the targeted medical therapy used for advanced or unresectable cases.

Question 39

Parents bring their 6-month-old infant with short-limbed dwarfism for evaluation. The child has hypotonia and hyperreflexia. An MRI of the cervicomedullary junction is ordered. What is the primary cause of the underlying pathology at this anatomical site in this condition?

Explanation

Achondroplasia results in defective endochondral ossification, which affects the long bones and the cranial base. This leads to a narrowed foramen magnum, which can cause cervicomedullary compression in infants.

Question 40

A 55-year-old male presents with deep knee pain. Radiographs reveal a permeative diaphyseal lesion in the distal femur. Biopsy confirms primary non-Hodgkin lymphoma of bone. Which of the following is true regarding this condition?

Explanation

Primary lymphoma of bone typically has a better 5-year survival rate compared to conventional osteosarcoma. Treatment primarily consists of systemic chemotherapy and radiation, not surgical resection.

Question 41

A 14-year-old boy has multiple painless bony protuberances around his knees and shoulders. Genetic testing reveals a mutation in the EXT1 gene. This mutation primarily affects which of the following cellular processes?

Explanation

Multiple Hereditary Exostoses (MHE) is caused by mutations in the EXT1 or EXT2 genes. These genes encode glycosyltransferases responsible for heparan sulfate synthesis, disrupting chondrocyte regulation at the physis.

Question 42

A 4-year-old girl with a history of multiple low-energy fractures, blue sclerae, and dentinogenesis imperfecta is started on pamidronate. What is the primary mechanism of action of this medication in treating her condition?

Explanation

Osteogenesis Imperfecta is treated medically with bisphosphonates like pamidronate. Bisphosphonates function by inhibiting osteoclast-mediated bone resorption, thereby increasing bone mineral density and reducing fracture risk.

Question 43

A 35-year-old male undergoes curettage and cementing for a giant cell tumor (GCT) of the proximal tibia. Two years later, a chest CT reveals multiple small, asymptomatic pulmonary nodules. Biopsy of a nodule confirms metastatic GCT. What is the most appropriate next step in management?

Explanation

Pulmonary metastases in GCT of bone are considered 'benign' implants and often have an indolent course. Management typically consists of observation, surgical resection if symptomatic and accessible, or targeted medical therapy like denosumab.

Question 44

A 40-year-old male with achondroplasia presents with progressive neurogenic claudication. He is diagnosed with severe lumbar spinal stenosis. Which of the following anatomical anomalies is the primary contributor to his stenosis?

Explanation

In achondroplasia, the pedicles are shortened and the interpedicular distance classically decreases from L1 to L5 (unlike the normal spine where it widens). This results in a congenitally narrow spinal canal and early-onset symptomatic spinal stenosis.

Question 45

A 25-year-old male presents with multiple asymmetric enchondromas predominantly involving the right side of his body, without any associated soft tissue vascular lesions. What is his estimated lifetime risk of malignant transformation to chondrosarcoma?

Explanation

The patient has Ollier disease (multiple enchondromatosis without hemangiomas). The lifetime risk of malignant transformation to chondrosarcoma in Ollier disease is approximately 25-30%.

Question 46

A newborn is evaluated for skeletal dysplasia. Physical examination reveals short limbs, clubfeet, 'hitchhiker' thumbs, and cystic swelling of the external ears (cauliflower ears). Which of the following gene mutations is most likely responsible for this phenotype?

Explanation

The clinical presentation is classic for diastrophic dysplasia. It is inherited in an autosomal recessive pattern due to a mutation in the SLC26A2 gene, which encodes a sulfate transporter.

Question 47

A 12-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 of the following cytogenetic abnormalities is most characteristic of this tumor?

Explanation

This presentation describes Ewing sarcoma. The most common translocation is t(11;22)(q24;q12), which results in the EWS-FLI1 fusion protein found in roughly 85% of cases.

Question 48

A 16-year-old boy presents with nocturnal back pain relieved by NSAIDs. Imaging reveals a 7mm intracortical nidus in the lamina of L4, located 4 mm from the traversing L4 nerve root. Which of the following is the most appropriate definitive management?

Explanation

The diagnosis is an osteoid osteoma. While radiofrequency ablation (RFA) is the treatment of choice for most locations, it is contraindicated when the nidus is within 1 cm of critical neural elements due to the risk of thermal nerve injury. Surgical excision is required.

Question 49

An adult patient with a known solitary enchondroma of the proximal humerus presents with new-onset, progressive pain at rest. Imaging reveals endosteal scalloping greater than two-thirds of the cortical thickness and cortical breakthrough. What is the most likely diagnosis?

Explanation

Pain at rest, deep endosteal scalloping (>2/3 of cortical thickness), and cortical breakthrough in a pre-existing cartilaginous lesion are strong indicators of malignant transformation to secondary chondrosarcoma.

Question 50

A 15-year-old boy presents with the ability to appose his shoulders at the midline. He has delayed eruption of permanent teeth and an unusually wide face. Radiographs show absent clavicles. This condition is primarily due to a defect in which of the following?

Explanation

Cleidocranial dysplasia is caused by a mutation in RUNX2 (CBFA1), an essential transcription factor for osteoblast differentiation. It primarily affects bones formed by intramembranous ossification, such as the clavicles and cranial vault.

Question 51

A 6-year-old boy presents with recurrent fractures, anemia, and hepatosplenomegaly. Radiographs reveal a 'bone-within-a-bone' appearance and generalized osteosclerosis. What is the most definitive curative treatment for the underlying systemic disease?

Explanation

Infantile malignant osteopetrosis is caused by defective osteoclast function. Because osteoclasts are derived from the hematopoietic monocyte-macrophage lineage, hematopoietic stem cell transplantation (HSCT) is the only curative treatment.

Question 52

A 32-year-old female presents with knee pain. Radiographs show an eccentric, lytic epiphyseal lesion in the distal femur.

Biopsy confirms multinucleated giant cells interspersed among mononuclear cells. Which genetic mutation is highly specific and diagnostic for this neoplasm?

Explanation

Giant cell tumor (GCT) of bone is strongly associated with mutations in the H3F3A gene, which are found in over 90% of cases. IDH1/2 mutations are seen in enchondromas/chondrosarcomas, while USP6 is characteristic of aneurysmal bone cysts.

Question 53

A 4-year-old boy with a known skeletal dysplasia presents for a routine evaluation.

Given his condition (achondroplasia), radiographs of the lumbar spine are most likely to demonstrate which of the following characteristic findings?

Explanation

In achondroplasia, the classic spinal radiographic finding is a narrowing (decreasing) of the interpedicular distance from L1 to L5. This predisposes patients to significant spinal stenosis later in life.

Question 54

A 45-year-old asymptomatic male has an incidental finding on a knee radiograph obtained after minor trauma.

The lesion is centrally located in the metaphysis, demonstrating stippled calcification without cortical destruction or periosteal reaction. What is the most appropriate next step in management?

Explanation

The clinical and radiographic presentation is classic for a benign enchondroma. Asymptomatic enchondromas without signs of aggressive behavior (e.g., endosteal scalloping > 2/3 of cortical thickness) are managed with observation.

Question 55

Primary bone lymphoma is a rare malignancy that most commonly affects the metaphysis or diaphysis of long bones.

Which of the following is the most significant prognostic factor for long-term survival in primary bone lymphoma?

Explanation

The clinical stage of the disease at the time of presentation is the most critical prognostic factor for survival in primary bone lymphoma. Localized disease has a significantly better 5-year survival rate compared to disseminated disease.

Question 56

A 6-year-old child presents with a history of frequent long bone fractures, blue sclerae, and early-onset hearing loss. A genetic defect in which of the following processes is primarily responsible for this clinical presentation?

Explanation

The patient has Osteogenesis Imperfecta, which is most commonly caused by mutations in the COL1A1 or COL1A2 genes. This leads to defective synthesis and triple helix formation of type I collagen, making bones brittle.

Question 57

A 12-year-old boy presents with localized pain, fever, and weight loss. Radiographs reveal a permeative lesion in the femoral diaphysis with an "onion-skin" periosteal reaction. Cytogenetic testing reveals a t(11;22) translocation. Which fusion protein is most commonly produced by this genetic alteration?

Explanation

Ewing sarcoma is characterized by the t(11;22)(q24;q12) translocation in approximately 85% of cases. This specific translocation results in the EWS-FLI1 fusion protein, which acts as an aberrant transcription factor.

Question 58

A 16-year-old male complains of chronic hip pain. Radiographs reveal a 2 cm well-circumscribed, lytic lesion in the greater trochanter apophysis with fine matrix calcifications. Histology shows polygonal mononuclear cells with clefted nuclei and "chicken-wire" calcification. What is the standard treatment?

Explanation

The presentation and histology (chicken-wire calcification, epiphyseal/apophyseal location) are classic for chondroblastoma. The standard treatment is intralesional curettage and bone grafting, as these lesions are benign but locally aggressive.

Question 59

A 25-year-old female presents with a progressive "shepherd's crook" deformity of her right proximal femur. She also reports a history of precocious puberty and has large, irregular café-au-lait macules. This condition is caused by a mutation in the GNAS gene, leading to overactivity of which cellular messenger?

Explanation

McCune-Albright syndrome (polyostotic fibrous dysplasia, endocrinopathy, café-au-lait spots) is caused by a somatic activating mutation in the GNAS gene. This results in constitutive activation of adenylate cyclase and increased intracellular cAMP.

Question 60

An infant presents with failure to thrive, hepatosplenomegaly, and severe anemia. Radiographs show diffusely dense bones with a "bone-within-bone" appearance in the metaphyses. A mutation impairing which of the following cellular mechanisms is most likely responsible?

Explanation

This is malignant infantile osteopetrosis, characterized by defective osteoclast function. Mutations often involve TCIRG1 or Carbonic Anhydrase II, preventing the osteoclast from acidifying the resorption pit and dissolving hydroxyapatite.

Question 61

A 14-year-old male with multiple painless, bony bumps around his knees and shoulders is diagnosed with Multiple Hereditary Exostoses (MHE). He asks about his risk of malignant transformation. The highest risk is malignant transformation into which of the following?

Explanation

Patients with Multiple Hereditary Exostoses (MHE) have a 1-5% lifetime risk of an osteochondroma undergoing malignant transformation. This almost exclusively transforms into a secondary peripheral chondrosarcoma.

Question 62

Denosumab is increasingly used in the neoadjuvant management of unresectable or complex giant cell tumors of bone.

What is the specific target of this monoclonal antibody?

Explanation

Denosumab is a monoclonal antibody that binds to RANK Ligand (RANKL), which is overexpressed by the neoplastic mononuclear stromal cells in giant cell tumors. This prevents RANKL from binding to the RANK receptor, thereby inhibiting osteoclast giant cell formation.

Question 63

A newborn is noted to have severe short-limbed dwarfism, a "hitchhiker" thumb deformity, clubfeet, and cystic swelling of the external ear (cauliflower ear). Which of the following genes is mutated in this autosomal recessive skeletal dysplasia?

Explanation

The clinical picture describes diastrophic dysplasia, which is caused by a mutation in the SLC26A2 gene. This gene encodes a sulfate transporter essential for proper cartilage matrix sulfation.

Question 64

A 5-year-old girl with normal intelligence, short-trunk dwarfism, and corneal clouding is diagnosed with Morquio syndrome (Mucopolysaccharidosis Type IV). Which orthopedic complication must be urgently screened for due to a high risk of catastrophic neurologic injury?

Explanation

Patients with Morquio syndrome are uniquely at high risk for atlantoaxial instability due to profound odontoid hypoplasia and ligamentous laxity. Screening cervical spine imaging is critical to prevent spinal cord compression.

Question 65

A 15-year-old patient is evaluated for delayed dental eruption, open cranial sutures, and abnormal shoulder mobility, allowing them to approximate their shoulders anteriorly. This autosomal dominant condition is caused by a mutation in the RUNX2 (CBFA1) gene. This gene normally controls the differentiation of which cell type?

Explanation

The patient has cleidocranial dysplasia. The RUNX2 (CBFA1) gene is a master transcription factor essential for osteoblast differentiation and subsequent intramembranous ossification.

Question 66

A 19-year-old male presents with severe nocturnal pain in the proximal tibia that is completely relieved by oral ibuprofen. Imaging shows a 1.2 cm radiolucent nidus surrounded by thick cortical sclerosis. Which specific cell type is primarily responsible for the excessive prostaglandin E2 (PGE2) production in this lesion?

Explanation

The lesion is an osteoid osteoma. The intense pain is mediated by high levels of prostaglandin E2 (PGE2), which is secreted directly by the neoplastic osteoblasts residing within the nidus.

Question 67

A 6-year-old child presents with short-limbed dwarfism, a waddling gait, and prominent joint laxity. Unlike achondroplasia, the child has a completely normal facial appearance. Radiographs show delayed epiphyseal ossification and irregular metaphyses. A mutation in which of the following genes is responsible?

Explanation

Pseudoachondroplasia is distinguished from achondroplasia by normal facies, normal intelligence, and marked joint laxity. It is caused by mutations in the Cartilage Oligomeric Matrix Protein (COMP) gene.

Question 68

A 15-year-old female presents with a rapidly enlarging, painful mass in her distal radius. Radiographs show an eccentric, expansile lytic lesion with a thin "eggshell" cortex. MRI reveals multiple fluid-fluid levels. Which genetic rearrangement is highly characteristic of the primary form of this lesion?

Explanation

Primary aneurysmal bone cysts (ABCs) are neoplastic processes driven by rearrangements of the USP6 gene (t(16;17)). Secondary ABCs (arising in GCT, chondroblastoma, etc.) do not typically harbor this mutation.

Question 69

A 65-year-old male presents with increasing hat size, asymmetric hearing loss, and bowing of his right tibia. Laboratory testing reveals markedly elevated alkaline phosphatase with normal serum calcium and phosphorus. Which phase of this specific disease process is characterized by intense, unregulated osteoclastic resorption?

Explanation

Paget's disease of bone begins with an initial lytic phase, characterized by aggressive, unregulated osteoclastic bone resorption. This is followed by a mixed phase and finally a sclerotic phase where weak, woven bone is haphazardly laid down.

Question 70

A 9-year-old boy sustains a pathologic fracture of the proximal humerus after a minor fall. Radiographs show a centrally located, cystic lesion in the metaphysis extending to the physis, featuring a "fallen leaf" sign. Which of the following statements is true regarding the classification of this lesion?

Explanation

Unicameral bone cysts (UBCs) are classified as 'active' if they are adjacent to (within 1 cm of) the physis. They are 'latent' if they have migrated away from the physis into the diaphysis as the bone grows.

Question 71

A 16-year-old male is undergoing treatment for conventional high-grade osteosarcoma of the distal femur. After completing neoadjuvant chemotherapy, wide surgical resection is performed. Which of the following histologic findings in the resected specimen is the most important predictor of long-term survival?

Explanation

The degree of tumor necrosis following neoadjuvant chemotherapy (Huvos grading) is the single most important prognostic indicator in osteosarcoma. Greater than 90% necrosis indicates a good histologic response and significantly better long-term survival.

Question 72

A 28-year-old female presents with severe knee pain. Radiographs reveal an eccentric, lytic epiphyseal-metaphyseal lesion in the proximal tibia.

Biopsy is consistent with a giant cell tumor of bone. Which of the following describes the primary neoplastic cell population in this lesion?

Explanation

The primary neoplastic cells in a Giant Cell Tumor of bone are the mononuclear spindle cells, which actively secrete RANKL. The multinucleated giant cells are reactive, non-neoplastic osteoclasts recruited by the RANKL expression.

Question 73

A 14-month-old male with achondroplasia presents with central sleep apnea, hyperreflexia, and hypotonia.

What is the most critical next step in his evaluation?

Explanation

Infants with achondroplasia are at high risk for foramen magnum stenosis, which can cause cervicomedullary compression leading to central sleep apnea, myelopathy, and sudden death. MRI of the craniovertebral junction is critical for evaluation and surgical planning for possible decompression.

Question 74

A 45-year-old asymptomatic male undergoes a shoulder radiograph following mild trauma, revealing a well-defined intramedullary lesion with punctate calcifications in the proximal humerus.

There is no endosteal scalloping or cortical breakthrough. What is the most appropriate management?

Explanation

The clinical and radiographic findings are classic for an asymptomatic, latent enchondroma. Without signs of aggressive behavior such as pain, deep endosteal scalloping (>2/3 of cortical thickness), or cortical breach, observation is the standard of care.

Question 75

A 60-year-old male presents with a painful, destructive lesion in his distal femur.

Biopsy confirms Primary Bone Lymphoma (Diffuse Large B-Cell type). Which of the following clinical factors portends the most favorable prognosis in this patient?

Explanation

Primary bone lymphoma generally has a better prognosis than systemic lymphoma with secondary bone metastasis. Favorable prognostic factors include younger age, solitary bone involvement, normal LDH levels, and the absence of B symptoms (fever, night sweats, weight loss).

Question 76

A 12-year-old male presents with a mixed lytic and sclerotic metaphyseal lesion of the distal femur with a 'sunburst' periosteal reaction. He has a history of poikiloderma, sparse hair, and bilateral cataracts. Which gene mutation is most likely responsible for his underlying syndrome?

Explanation

The patient's presentation of osteosarcoma coupled with poikiloderma, alopecia, and cataracts is classic for Rothmund-Thomson syndrome. This autosomal recessive disorder is caused by a mutation in the RECQL4 DNA helicase gene, significantly increasing the risk of osteosarcoma.

Question 77

A 14-year-old male presents with severe mid-thigh pain, swelling, and low-grade fever. Radiographs show a permeative diaphyseal lesion with an 'onion-skin' periosteal reaction. Molecular testing of the biopsy specimen is most likely to reveal which of the following translocations?

Explanation

Ewing sarcoma is classically characterized by the t(11;22) translocation, resulting in the EWS-FLI1 fusion protein. This oncogenic fusion occurs in approximately 85-90% of Ewing sarcoma cases.

Question 78

A 16-year-old male complains of chronic right knee pain. Radiographs show a 2 cm eccentric, purely lytic lesion in the proximal tibial epiphysis with a thin sclerotic rim. Histological examination shows mononuclear cells with grooved nuclei and areas of pericellular 'chicken-wire' calcification. What is the most likely diagnosis?

Explanation

Chondroblastoma typically presents as an epiphyseal lytic lesion in skeletally immature patients. The histologic hallmark is the presence of chondroblasts with grooved 'coffee bean' nuclei and distinctive 'chicken-wire' calcifications.

Question 79

A 7-year-old girl is evaluated for delayed eruption of secondary teeth. Examination reveals a persistently open anterior fontanelle, hypermobility of the shoulders allowing them to meet in the midline, and short stature. The gene responsible for this condition is critical for the differentiation of which cell type?

Explanation

The patient has cleidocranial dysplasia, caused by an autosomal dominant mutation in the RUNX2 (CBFA1) gene. RUNX2 is a master transcription factor essential for osteoblast differentiation and subsequent intramembranous and endochondral ossification.

Question 80

A 32-year-old female presents with progressive knee pain. Radiographs reveal an eccentric, lytic epiphyseal lesion extending to the subchondral bone in the distal femur.

Biopsy confirms a giant cell tumor. She is treated preoperatively with a monoclonal antibody to facilitate joint salvage. What is the primary mechanism of action of this medication?

Explanation

Denosumab is a monoclonal antibody that binds to RANKL, preventing it from activating RANK on osteoclast-like giant cells and their precursors. In giant cell tumor of bone, it is used to consolidate the tumor, reducing its vascularity and promoting a neocortical rim to facilitate surgical curettage.

Question 81

An 8-month-old infant with achondroplasia presents with delayed motor milestones, hypotonia, and witnessed episodes of central sleep apnea.

What is the most appropriate next step in evaluation?

Explanation

Infants with achondroplasia are at high risk for foramen magnum stenosis, leading to cervicomedullary compression that presents with hypotonia, hyperreflexia, or central sleep apnea. MRI of the craniocervical junction is the gold standard for diagnosing this potentially lethal complication, which requires urgent surgical suboccipital decompression.

Question 82

A 45-year-old male sustains a minor twisting injury to his hand. Radiographs show a well-circumscribed, lucent lesion with central stippled calcifications in the proximal phalanx of the ring finger.

There is no cortical breakthrough. Which of the following mutations is most frequently associated with the development of multiple such lesions in a mostly unilateral or asymmetric distribution?

Explanation

The patient has an enchondroma. Multiple enchondromas with a unilateral or asymmetric distribution characterize Ollier disease, which is driven by somatic mosaic mutations in the IDH1 or IDH2 genes. EXT1 mutations are associated with multiple hereditary exostoses, not enchondromatosis.

Question 83

A 60-year-old male presents with worsening thigh pain over several months. Radiographs demonstrate a permeative, poorly marginated radiolucent lesion in the femoral diaphysis.

MRI reveals extensive soft tissue and marrow involvement that appears vastly out of proportion to the subtle cortical destruction. What is the most likely diagnosis?

Explanation

Primary lymphoma of bone often presents with extensive intramedullary marrow replacement and a large associated soft tissue mass. The striking 'mismatch' between the aggressive MRI appearance (large soft tissue/marrow mass) and the relatively preserved cortical bone on radiographs is a classic hallmark of this tumor.

Question 84

A 45-year-old female undergoes an MRI of her shoulder for suspected rotator cuff pathology. An incidental lesion is found in the proximal humerus, corresponding to punctate calcifications seen on plain radiographs. MRI shows a lobulated high T2 signal lesion with no endosteal scalloping or cortical breakthrough.

What is the most appropriate management for this bone lesion?

Explanation

This is an incidental enchondroma, characterized by punctate calcifications and lack of aggressive features like endosteal scalloping or pain. Asymptomatic enchondromas in the appendicular skeleton are safely managed with observation. Surgical intervention is reserved for symptomatic lesions or those showing signs of malignant transformation.

Question 85

A 25-year-old female presents with progressive knee pain. Radiographs reveal an eccentric, expansile, lytic lesion in the distal femoral epiphysis extending to the subchondral bone plate. Biopsy confirms a giant cell tumor of bone.

If pharmacological therapy with denosumab is considered, this drug specifically targets which of the following mechanisms in this pathology?

Explanation

Denosumab is a monoclonal antibody that binds to RANKL. In giant cell tumor of bone, RANKL is overexpressed and secreted by the neoplastic mononuclear stromal cells, not the giant cells. This drives the recruitment and activation of the reactive osteoclast-like giant cells that cause bone destruction.

Question 86

A 4-year-old boy with achondroplasia presents with lower extremity hyperreflexia, clumsiness, and central sleep apnea.

What is the most likely anatomic cause of these symptoms?

Explanation

Foramen magnum stenosis is a critical and potentially lethal complication in infants and young children with achondroplasia. It presents with myelopathy (hyperreflexia, clonus), central sleep apnea, and respiratory difficulties, requiring urgent neurosurgical decompression.

Question 87

A 50-year-old male presents with deep thigh pain. Radiographs demonstrate a poorly defined, permeative lytic lesion in the femoral diaphysis with minimal cortical destruction. MRI reveals extensive marrow replacement and a large surrounding soft tissue mass.

Which of the following statements best describes primary lymphoma of bone compared to other primary bone malignancies?

Explanation

Primary lymphoma of bone classically presents with extensive marrow involvement and soft tissue extension despite minimal cortical destruction on plain radiographs. Unlike osteosarcoma, it lacks osteoid production, and unlike Ewing sarcoma, t(11;22) is not characteristic. It is highly sensitive to chemoradiation.

Question 88

A 10-year-old boy is referred for delayed eruption of his permanent teeth, prominent frontal bossing, and excessive shoulder mobility. Radiographs demonstrate hypoplastic clavicles and delayed ossification of the pubic symphysis. A mutation in which of the following transcription factors is responsible for this condition?

Explanation

The patient has cleidocranial dysplasia, an autosomal dominant disorder caused by a mutation in the RUNX2 (CBFA1) gene on chromosome 6. RUNX2 is a master transcription factor essential for osteoblast differentiation and intramembranous ossification.

Question 89

An 18-year-old male presents with rapid onset of pain and swelling over his distal thigh following minor trauma. Radiographs reveal a purely lytic, expansile metaphyseal lesion with cortical destruction. Biopsy shows blood-filled cystic spaces separated by septa containing highly pleomorphic spindle cells and fine, lace-like osteoid. What is the most likely diagnosis?

Explanation

Telangiectatic osteosarcoma radiographically mimics an aneurysmal bone cyst (ABC) due to its cystic, expansile nature and fluid-fluid levels on MRI. However, the histopathology shows high-grade sarcomatous cells and malignant osteoid in the septa, distinguishing it from a benign ABC.

Question 90

A 12-year-old boy presents with multiple hard, painless masses around his knees and ankles. Radiographs demonstrate multiple bone excrescences pointing away from the joints, with continuity of the medullary cavity into the lesions. What is the underlying pathogenesis of this condition?

Explanation

Multiple hereditary exostoses (MHE) is caused by autosomal dominant mutations in EXT1 or EXT2. These genes encode glycosyltransferases responsible for heparan sulfate synthesis, leading to disorganized Indian hedgehog signaling and abnormal chondrocyte proliferation.

Question 91

A 7-year-old boy complains of localized mid-back pain for several weeks. A lateral radiograph of the thoracic spine reveals a "vertebra plana" at T8 with preserved disc spaces. Laboratory studies are normal. Electron microscopy of a biopsy specimen from this lesion would most likely reveal which of the following structures?

Explanation

The clinical picture of vertebra plana in a child is highly suspicious for Langerhans cell histiocytosis (eosinophilic granuloma). The pathognomonic electron microscopic finding for Langerhans cells is the presence of Birbeck granules, which are tennis-racket shaped cytoplasmic organelles.

Question 92

An infant born at 38 weeks gestation is noted to have profound osteopenia, severe limb deformities with multiple acute and healing fractures, and deep blue sclerae. The infant succumbs to respiratory failure secondary to a small, frail thorax shortly after birth. According to the Sillence classification, which type of osteogenesis imperfecta does this patient have?

Explanation

Sillence Type II osteogenesis imperfecta is the perinatal lethal form. It is characterized by severe bone fragility, multiple in utero fractures, profound deformities, and death in the neonatal period, typically due to pulmonary hypoplasia and respiratory failure.

Question 93

A 15-year-old male presents with chronic knee pain. Radiographs display a well-circumscribed, eccentrically located lytic lesion with a thin sclerotic margin in the proximal tibial epiphysis. Biopsy shows polygonal mononuclear cells with longitudinally clefted nuclei and areas of "chicken-wire" intercellular calcification. Following extended curettage and bone grafting, what is the most common complication of this lesion?

Explanation

The diagnosis is chondroblastoma, a benign but locally aggressive epiphyseal tumor characterized by clefted nuclei and "chicken-wire" calcification. The most common complication following intralesional curettage is local recurrence, occurring in approximately 10-20% of cases.

Question 94

A 9-year-old girl is evaluated for a limp and a leg-length discrepancy. Physical exam notes large café-au-lait macules with irregular, "coast of Maine" borders. She also has a history of early-onset menses. Radiographs show a polyostotic intramedullary lesion with a hazy, "ground-glass" appearance. This clinical syndrome is associated with a mutation affecting which of the following?

Explanation

McCune-Albright syndrome consists of polyostotic fibrous dysplasia, precocious puberty, and café-au-lait spots. It is caused by a somatic activating mutation in the GNAS gene, which encodes the Gs alpha subunit of adenylyl cyclase, leading to continuous cAMP production.

Question 95

A 65-year-old man presents with severe back pain. Radiographs show multiple dense, osteoblastic lesions throughout the lumbar spine and pelvis. Laboratory evaluation reveals a significantly elevated serum prostate-specific antigen (PSA). The osteoblastic nature of these skeletal metastases is primarily driven by tumor secretion of which factor?

Explanation

Prostate cancer uniquely produces osteoblastic (bone-forming) metastases. This process is driven by the tumor cells secreting factors that stimulate osteoblasts, most notably Endothelin-1 (ET-1) and bone morphogenetic proteins (BMPs). PTHrP is more commonly associated with osteolytic breast cancer metastases.

Question 96

A newborn is evaluated in the NICU for marked shortening of all limbs, proximally placed "hitchhiker" thumbs, severe clubfeet, and distinct cystic swelling of the pinnae (cauliflower ears). Radiographs show short, thick long bones and a normal skull. The underlying genetic mutation in this condition primarily impairs which cellular process?

Explanation

Diastrophic dysplasia is caused by an autosomal recessive mutation in the SLC26A2 (DTDST) gene. This gene encodes a sulfate transporter, leading to intracellular sulfate depletion, undersulfation of proteoglycans in the cartilage matrix, and abnormal chondrocyte function.

Question 97

A 30-year-old female presents with a slow-growing, mildly painful mass in her anterior shin. Plain radiographs reveal an eccentric, multi-loculated, "soap-bubble" osteolytic lesion in the anterior tibial diaphysis. Histology shows nests of epithelial cells within a fibrous stroma. Which of the following conditions is most frequently considered a precursor or is commonly found coexisting with this specific tumor?

Explanation

The patient has an adamantinoma, a rare, low-grade malignant bone tumor that almost exclusively occurs in the anterior tibial diaphysis. It is frequently associated with, or thought to evolve from, osteofibrous dysplasia (Campanacci disease), which shares overlapping clinical and histologic features.

Question 98

A 25-year-old male with a known history of Ollier disease presents with new, rapidly worsening pain and a palpable mass in his proximal humerus. Radiographs show a previously stable enchondroma that now exhibits cortical destruction and a soft tissue mass containing rings-and-arcs calcifications.

What is the most likely diagnosis of this new aggressive lesion?

Explanation

Patients with Ollier disease (multiple enchondromatosis) have a high risk (up to 30-50%) of malignant transformation. The most common malignancy to arise from a pre-existing enchondroma is a secondary conventional chondrosarcoma, indicated here by cortical destruction and cartilaginous matrix outside the bone.

Question 99

A 12-month-old infant with achondroplasia presents for a routine check-up. The parents note a prominent outward curve in the child's lower back when sitting upright. Radiographs confirm a moderate thoracolumbar kyphosis.

What is the most appropriate initial management for this spinal finding?

Explanation

Thoracolumbar kyphosis is common in infants with achondroplasia due to generalized hypotonia and relatively large head size. The vast majority (>90%) will spontaneously resolve once the child begins to walk and develop lumbar lordosis. Initial management consists of avoiding unsupported sitting and observation.

Skeletal Dysplasias of the Spine - Arab Board MCQ Prep

Master ABOS Orthopedic Board Review: Bone Tumors & Skeletal Dysplasias | Part 10

Key Takeaway

Master ABOS Orthopedic Board Review: Bone Tumors & Skeletal Dysplasias | Part 10

Chapter Index