Menu

10. Pathology and Oncology MCQs

Practice Set 144 of 351

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

Question 2861

Topic: 10. Pathology and Oncology

A 14-year-old girl presents with pain and a rapidly expanding mass in her proximal humerus following a minor fall. Radiographs demonstrate an eccentrically located, expansile, purely lytic metaphyseal lesion. MRI exhibits multiple fluid-fluid levels within the lesion. Histological analysis of a core biopsy demonstrates blood-filled cystic spaces separated by fibrous septa containing multinucleated giant cells, with no significant atypia. Which of the following genetic alterations is most characteristic of the primary form of this specific lesion?

. GNAS1 mutation
. EXT1 mutation
. USP6 (17p13) rearrangement
. H3F3A (Histone 3.3) mutation
. p53 mutation

Correct Answer & Explanation

. USP6 (17p13) rearrangement

Explanation

The clinical, radiographic, and MRI findings (fluid-fluid levels) are classic for an Aneurysmal Bone Cyst (ABC). While secondary ABCs can arise in the setting of other bone tumors (like GCTB or chondroblastoma), primary ABCs are now recognized as distinct neoplastic processes. They are characterized by rearrangements of the USP6 gene on chromosome 17p13, which leads to upregulation of matrix metalloproteinases and vascular endothelial growth factors. GNAS1 mutations are associated with Fibrous Dysplasia. EXT1/EXT2 are seen in Multiple Hereditary Exostoses. H3F3A mutations are classically seen in Giant Cell Tumor of Bone (GCTB) and Chondroblastoma.

Question 2862

Topic: Bone Tumors

A 19-year-old man reports a 6-month history of right thigh pain that is particularly severe at night and brings him out of sleep. He notes that taking over-the-counter ibuprofen provides dramatic and near-complete relief for several hours. Radiographs show profound diaphyseal cortical thickening with a 7-mm radiolucent nidus. The intense pain and the specific response to nonsteroidal anti-inflammatory drugs (NSAIDs) in this condition are directly related to the high local concentration of which of the following mediators?

. Interleukin-1 (IL-1)
. Tumor necrosis factor-alpha (TNF-alpha)
. Prostaglandin E2 (PGE2)
. Substance P
. Transforming growth factor-beta (TGF-beta)

Correct Answer & Explanation

. Prostaglandin E2 (PGE2)

Explanation

The presentation of night pain dramatically relieved by NSAIDs, combined with a small radiolucent nidus surrounded by dense reactive cortical bone, is pathognomonic for an osteoid osteoma. The nidus of an osteoid osteoma produces abnormally high levels of cyclooxygenase-2 (COX-2) and its downstream product, Prostaglandin E2 (PGE2). PGE2 mediates both the intense localized pain and the dense reactive bone formation surrounding the lesion. The dramatic pain relief provided by NSAIDs is directly attributable to their inhibition of COX, which halts PGE2 synthesis.

Question 2863

Topic: 10. Pathology and Oncology

A 28-year-old male presents with a slowly enlarging, deep, tender mass in the plantar aspect of his left foot, which he noticed two years ago. MRI demonstrates a well-circumscribed soft tissue mass intimately associated with the plantar fascia, exhibiting heterogeneous hyperintensity on T2-weighted imaging. A core needle biopsy reveals a biphasic pattern of spindle cells and epithelial cells forming glandular structures. What is the most definitive diagnostic molecular finding for this tumor?

. MDM2 gene amplification
. t(X;18)(p11;q11) leading to SS18-SSX fusion
. Beta-catenin (CTNNB1) point mutation
. t(2;13)(q35;q14) leading to PAX3-FOXO1 fusion
. MYC gene amplification

Correct Answer & Explanation

. t(X;18)(p11;q11) leading to SS18-SSX fusion

Explanation

The patient's clinical presentation (a slow-growing soft tissue mass in the distal extremity of a young adult) and classic biphasic histology (spindle and epithelial components) are highly indicative of Synovial Sarcoma. Despite the historical name, it rarely arises from actual synovial tissue. The defining cytogenetic abnormality, present in over 95% of synovial sarcomas, is the t(X;18)(p11;q11) translocation. This fuses the SS18 (formerly SYT) gene on chromosome 18 with one of the SSX genes (SSX1, SSX2, or SSX4) on the X chromosome. MDM2 amplification is characteristic of atypical lipomatous tumors/well-differentiated liposarcomas. Beta-catenin mutations are typical of desmoid fibromatosis.

Question 2864

Topic: 10. Pathology and Oncology

A 14-year-old boy complains of worsening distal femur pain for 3 months, predominantly occurring at night and unassociated with activity. Radiographs demonstrate a mixed lytic and sclerotic lesion in the distal femoral metaphysis with a distinct 'sunburst' periosteal reaction.

In addition to securing a core needle biopsy, understanding the genetic basis is crucial. Which of the following genetic alterations is most strongly associated with the pathogenesis of this patient's likely diagnosis?

. t(11;22) chromosomal translocation
. Mutation in the EXT1 or EXT2 gene
. Mutations in the RB1 and TP53 genes
. t(X;18) chromosomal translocation
. Activating mutation in the GNAS gene

Correct Answer & Explanation

. Mutations in the RB1 and TP53 genes

Explanation

The clinical presentation and radiographic findings (sunburst periosteal reaction, mixed lytic/sclerotic lesion in the metaphysis) are classic for osteosarcoma. Osteosarcoma pathogenesis is highly associated with mutations in the RB1 (retinoblastoma) and TP53 (Li-Fraumeni syndrome) tumor suppressor genes. Option A is characteristic of Ewing sarcoma; Option B represents multiple hereditary exostoses; Option D is synovial sarcoma; and Option E is associated with fibrous dysplasia (McCune-Albright syndrome).

Question 2865

Topic: 10. Pathology and Oncology

An 11-year-old girl presents with an ill-defined, permeative lytic lesion in the diaphysis of the femur with a prominent soft tissue mass and "onion-skin" periosteal reaction. Biopsy confirms Ewing sarcoma. Which of the following chromosomal translocations is most commonly associated with this diagnosis?

. t(11;22)(q24;q12)
. t(9;22)(q34;q11)
. t(2;13)(q35;q14)
. t(12;16)(q13;p11)
. t(X;18)(p11;q11)

Correct Answer & Explanation

. t(11;22)(q24;q12)

Explanation

Ewing sarcoma is classically driven by the t(11;22)(q24;q12) chromosomal translocation. This creates the pathognomonic EWS-FLI1 fusion protein found in approximately 85% of cases.

Question 2866

Topic: 10. Pathology and Oncology

A 12-year-old boy presents with thigh pain and a low-grade fever. Radiographs show a permeative diaphyseal lesion of the femur with an "onion-skin" periosteal reaction. Biopsy reveals sheets of small round blue cells. Which chromosomal translocation is highly diagnostic for this tumor?

. t(9;22)
. t(11;22)
. t(X;18)
. t(12;16)
. t(2;13)

Correct Answer & Explanation

. t(11;22)

Explanation

Ewing sarcoma is a small round blue cell tumor classically presenting with an "onion-skin" periosteal reaction in the diaphysis of long bones. It is highly associated with the t(11;22) chromosomal translocation, which results in the EWS-FLI1 fusion protein.

Question 2867

Topic: 10. Pathology and Oncology

An 11-year-old girl presents with a painful, swollen mass on her distal thigh. A biopsy reveals uniform small round blue cells. Cytogenetic analysis of the tumor tissue is most likely to show which of the following chromosomal translocations?

. t(9;22)
. t(X;18)
. t(12;16)
. t(2;13)
. t(11;22)

Correct Answer & Explanation

. t(11;22)

Explanation

Ewing sarcoma is a classic small round blue cell tumor strongly associated with the chromosomal translocation t(11;22)(q24;q12). This specific translocation results in the EWS-FLI1 fusion protein, which is diagnostic in approximately 85% of cases.

Question 2868

Topic: 10. Pathology and Oncology

A 15-year-old boy presents with a painful mass in the distal femur. A biopsy reveals small, round blue cells. Molecular testing demonstrates a t(11;22)(q24;q12) chromosomal translocation. This specific genetic alteration results in the fusion of which two genes, characteristic of the diagnosed lesion?

. SYT-SSX
. TLS-CHOP
. EWS-FLI1
. PAX3-FKHR
. MDM2-CDK4

Correct Answer & Explanation

. EWS-FLI1

Explanation

The t(11;22)(q24;q12) translocation is found in approximately 85% of Ewing sarcomas. This translocation fuses the EWSR1 (Ewing sarcoma breakpoint region 1) gene on chromosome 22 with the FLI1 (Friend leukemia integration 1) gene on chromosome 11, resulting in the EWS-FLI1 fusion protein, which acts as an aberrant transcription factor. SYT-SSX is associated with synovial sarcoma; TLS-CHOP with myxoid liposarcoma; PAX3-FKHR with alveolar rhabdomyosarcoma; and MDM2/CDK4 amplification with well-differentiated liposarcomas and parosteal osteosarcoma.

Question 2869

Topic: 10. Pathology and Oncology

A 14-year-old boy presents with a 2-month history of pain and swelling in his left thigh. Plain radiographs show a permeative, destructive diaphyseal lesion in the femur with an 'onion skin' periosteal reaction. Biopsy reveals uniform, small, round blue cells that stain positive for CD99. Cytogenetic analysis is most likely to show which of the following chromosomal translocations?

. t(11;22)
. t(9;22)
. t(X;18)
. t(2;13)
. t(12;16)

Correct Answer & Explanation

. t(11;22)

Explanation

The diagnosis is Ewing sarcoma, a highly malignant bone tumor seen most commonly in children and adolescents. It classically presents with a permeative diaphyseal lesion and 'onion skin' (lamellated) periosteal reaction. Histologically, it is a small round blue cell tumor. It is defined by the t(11;22)(q24;q12) translocation in over 90% of cases, which fuses the EWS gene on chromosome 22 to the FLI1 gene on chromosome 11. The t(X;18) translocation is associated with synovial sarcoma; t(2;13) is seen in alveolar rhabdomyosarcoma; and t(12;16) is seen in myxoid liposarcoma.

Question 2870

Topic: 10. Pathology and Oncology
In a 16-year-old patient diagnosed with localized, conventional high-grade osteosarcoma of the distal femur, which of the following clinical or pathologic factors is considered the most significant prognostic indicator for overall long-term survival?
. Age and gender at diagnosis
. Histologic subtype (osteoblastic vs. chondroblastic)
. Percentage of tumor necrosis following neoadjuvant chemotherapy
. Initial tumor volume on MRI
. Presence of an elevated serum alkaline phosphatase level pre-biopsy

Correct Answer & Explanation

. Percentage of tumor necrosis following neoadjuvant chemotherapy

Explanation

The degree of tumor necrosis following neoadjuvant chemotherapy is the single most important and reliable prognostic factor for patients with non-metastatic, conventional high-grade osteosarcoma. A 'good response' is typically defined as greater than 90% necrosis (Huvos grade III or IV) and is associated with significantly improved disease-free and overall survival.

Question 2871

Topic: 10. Pathology and Oncology

A 28-year-old man presents with a slow-growing, painful mass around his right knee, deep to the fascia. MRI shows a soft tissue mass, and plain radiographs demonstrate focal calcifications within the lesion. Core needle biopsy demonstrates a biphasic pattern of epithelial and spindle cells. What is the most appropriate initial management for this localized disease?

. Marginal excision alone
. Neoadjuvant radiation therapy followed by wide surgical resection
. Chemotherapy alone
. Intralesional curettage and bone grafting
. Primary above-knee amputation

Correct Answer & Explanation

. Neoadjuvant radiation therapy followed by wide surgical resection

Explanation

The patient has a synovial sarcoma, which frequently presents as a slow-growing mass in the extremities of young adults, often with focal calcifications on plain radiographs. It is a high-grade soft tissue sarcoma. The standard of care for localized, high-grade soft tissue sarcomas of the extremity involves wide surgical excision. Radiation therapy (either neoadjuvant or adjuvant) is highly recommended to improve local control rates. Marginal excision alone is associated with a high recurrence rate.

Question 2872

Topic: 10. Pathology and Oncology
A 55-year-old man presents with an enlarging, painful mass in his proximal humerus. Radiographs show a lytic lesion with intralesional 'popcorn' calcifications and deep endosteal scalloping greater than two-thirds of the cortical thickness. Biopsy confirms a Grade II (intermediate) conventional chondrosarcoma. What is the most appropriate definitive treatment?
. Intralesional curettage, adjuvant phenol, and cementation
. Wide surgical resection
. Neoadjuvant chemotherapy followed by wide resection
. Definitive external beam radiation therapy
. Systemic therapy with denosumab

Correct Answer & Explanation

. Wide surgical resection

Explanation

Conventional chondrosarcomas are generally radio-resistant and chemo-resistant. Therefore, the mainstay of treatment is surgical. For intermediate-grade (Grade II) and high-grade (Grade III) chondrosarcomas, wide surgical resection with negative margins is required to minimize the risk of local recurrence and metastasis. Intralesional curettage with adjuvants is generally reserved for low-grade (Grade I) chondrosarcomas (atypical cartilaginous tumors) in the appendicular skeleton.

Question 2873

Topic: Bone Tumors
A 62-year-old man presents with diffuse back and rib pain. Radiographs show multiple punched-out lytic lesions in the skull and pelvis. Laboratory evaluation reveals hypercalcemia, renal insufficiency, and anemia. Bone marrow aspirate shows >10% clonal plasma cells. Which of the following laboratory abnormalities is most strongly associated with a poor overall survival prognosis in this disease?
. Elevated serum calcium
. Decreased serum albumin
. Elevated serum beta-2 microglobulin
. Presence of Bence Jones proteins in the urine
. Elevated serum alkaline phosphatase

Correct Answer & Explanation

. Elevated serum beta-2 microglobulin

Explanation

The patient's presentation is diagnostic of multiple myeloma (CRAB criteria: hyperCalcemia, Renal insufficiency, Anemia, Bone lesions). The Revised International Staging System (R-ISS) for multiple myeloma relies heavily on serum beta-2 microglobulin and serum albumin levels, along with LDH and high-risk chromosomal abnormalities. An elevated beta-2 microglobulin (>5.5 mg/L) is the most significant biochemical indicator of high tumor burden, diminished renal function, and poor prognosis.

Question 2874

Topic: Bone Tumors

A 20-year-old woman is incidentally found to have a proximal femoral lesion during imaging for a hip strain. The radiograph shows a diaphyseal 'ground-glass' appearance surrounded by a sclerotic rim, with mild varus bowing. She has no endocrine abnormalities or cafe-au-lait spots. The underlying genetic mutation for this bony lesion involves which of the following?

. GNAS1 mutation leading to increased cAMP
. EXT1 mutation leading to abnormal heparan sulfate synthesis
. RET proto-oncogene mutation
. APC gene mutation
. p53 mutation

Correct Answer & Explanation

. GNAS1 mutation leading to increased cAMP

Explanation

The radiographic description ('ground-glass' matrix, mild bowing deformity) is classic for fibrous dysplasia. Fibrous dysplasia (both monostotic and polyostotic forms, as well as McCune-Albright syndrome) is caused by a somatic, activating postzygotic mutation in the GNAS1 gene. This gene encodes the alpha subunit of the stimulatory G protein (Gs). The mutation causes constitutive activation of adenylate cyclase, leading to increased intracellular cAMP, which results in the abnormal differentiation of osteoblasts and replacement of normal medullary bone with fibrous stroma.

Question 2875

Topic: Bone Tumors

A 16-year-old boy complains of persistent anterior thigh pain that has worsened over the past 4 months. He notes the pain is significantly worse at night and is dramatically relieved within 30 minutes of taking ibuprofen. Radiographs demonstrate a diaphyseal cortical thickening with a 1-cm central radiolucent nidus. What is the pathophysiologic mechanism responsible for the characteristic pain in this condition?

. Increased local concentration of prostaglandins, specifically PGE2
. Local compression of terminal branches of the femoral nerve
. Increased local production of interleukin-6 and TNF-alpha
. Rapid expansion of the periosteum due to aggressive tumor growth
. Accumulation of bradykinin in the surrounding muscle tissues

Correct Answer & Explanation

. Increased local concentration of prostaglandins, specifically PGE2

Explanation

The classic presentation of an osteoid osteoma includes intense, localized pain that is worse at night and dramatically relieved by NSAIDs. Pathologically, the central nidus of an osteoid osteoma produces very high levels of prostaglandins, particularly PGE2. This high local concentration of prostaglandins stimulates sensory nerve endings within the lesion, causing the intense pain. NSAIDs work by inhibiting cyclooxygenase (COX), thereby blocking prostaglandin synthesis and providing rapid pain relief.

Question 2876

Topic: 10. Pathology and Oncology

A 28-year-old man presents with a slow-growing, painless mass in the popliteal fossa of his left knee. Biopsy reveals a biphasic tumor with both epithelial and spindle cell components. Immunohistochemistry is positive for cytokeratin and epithelial membrane antigen (EMA). Which of the following chromosomal translocations is most characteristic of this lesion?

. t(11;22)
. t(X;18)
. t(12;16)
. t(9;22)
. t(2;13)

Correct Answer & Explanation

. t(X;18)

Explanation

The clinical and histological description is classic for synovial sarcoma, which frequently presents as a deep-seated mass near a joint in young adults. Histologically, it can be biphasic (containing both epithelial and spindle cells) or monophasic. Synovial sarcoma is characterized by the t(X;18)(p11;q11) translocation, leading to the SYT-SSX fusion gene. t(11;22) is characteristic of Ewing sarcoma; t(12;16) is seen in myxoid liposarcoma; t(9;22) is associated with extraskeletal myxoid chondrosarcoma; and t(2;13) is found in alveolar rhabdomyosarcoma.

Question 2877

Topic: 10. Pathology and Oncology

A 15-year-old boy presents with knee pain and a destructive, bone-forming lesion in the proximal tibia. Biopsy confirms high-grade intramedullary osteosarcoma. Mutations in which of the following pairs of tumor suppressor genes are most frequently associated with the pathogenesis of this disease?

. RB1 and TP53
. BRCA1 and APC
. NF1 and PTEN
. EXT1 and EXT2
. VHL and RET

Correct Answer & Explanation

. RB1 and TP53

Explanation

High-grade conventional osteosarcoma is highly associated with mutations in the retinoblastoma (RB1) and TP53 tumor suppressor genes. Patients with hereditary retinoblastoma (germline RB1 mutation) and Li-Fraumeni syndrome (germline TP53 mutation) have a significantly increased risk of developing osteosarcoma. EXT1 and EXT2 are associated with multiple hereditary exostoses, which can degenerate into chondrosarcoma, not osteosarcoma.

Question 2878

Topic: 10. Pathology and Oncology

A 9-year-old boy presents with a painful, swollen mid-thigh. Radiographs reveal a permeative diaphyseal lesion in the femur with a prominent 'onion-skin' periosteal reaction.

Histology shows sheets of uniform small round blue cells that stain strongly positive for CD99. Which of the following fusion proteins is most likely driving this malignancy?

. EWS-FLI1
. SYT-SSX1
. BCR-ABL
. TLS-CHOP
. PAX3-FKHR

Correct Answer & Explanation

. EWS-FLI1

Explanation

The clinical, radiographic, and histological presentation is classic for Ewing sarcoma. Ewing sarcoma typically presents in the diaphysis of long bones in children, showing a permeative lytic lesion with lamellated ('onion-skin') periostitis. It is a small round blue cell tumor that typically expresses CD99 (MIC2). The genetic hallmark is the t(11;22)(q24;q12) translocation, which produces the EWS-FLI1 fusion protein in approximately 85-90% of cases.

Question 2879

Topic: 10. Pathology and Oncology

A 14-year-old boy presents with pain and swelling in his left thigh. Radiographs reveal a permeative, lytic lesion in the diaphysis of the femur with an 'onion-skin' periosteal reaction. A biopsy is performed, showing sheets of uniform, small, round blue cells. Which of the following chromosomal translocations is most strongly associated with this diagnosis?

. t(11;22)(q24;q12)
. t(X;18)(p11;q11)
. t(12;16)(q13;p11)
. t(9;22)(q34;q11)
. t(2;13)(q35;q14)

Correct Answer & Explanation

. t(11;22)(q24;q12)

Explanation

The clinical presentation and biopsy describe Ewing sarcoma. The classic translocation for Ewing sarcoma is t(11;22)(q24;q12), which results in the EWS-FLI1 fusion protein. Synovial sarcoma is associated with t(X;18). Myxoid liposarcoma is associated with t(12;16). Alveolar rhabdomyosarcoma is associated with t(2;13).

Question 2880

Topic: Bone Tumors

A 19-year-old man presents with severe right leg pain that is worse at night and dramatically improves with NSAIDs. Radiographs show a sclerotic lesion in the tibial diaphysis with a small central radiolucent nidus. The intense pain associated with this lesion is primarily mediated by high levels of which of the following within the nidus?

. Substance P
. Prostaglandin E2
. Interleukin-1
. Tumor necrosis factor-alpha
. Bradykinin

Correct Answer & Explanation

. Prostaglandin E2

Explanation

The clinical presentation is classic for an osteoid osteoma. The pain is characteristically severe, worse at night, and relieved by NSAIDs. This is because the nidus of an osteoid osteoma produces high levels of prostaglandins, particularly Prostaglandin E2 (PGE2), which mediates the pain response and local vasodilation. NSAIDs block the cyclooxygenase (COX) enzyme, thereby decreasing PGE2 production and relieving pain.

Test Yourself

Switch to an interactive, timed exam simulation to truly master this topic.

On this Page