Bone and Soft Tissue Pathology Practice Questions

Q: A 4-year-old boy is brought to the physician by his parents due to frequent falls, inability to jump, and easy fatigue. Physical examination reveals weakness in the pelvic and shoulder girdles, as well as enlargement of the child's calf muscles. The serum level of creatine kinase is elevated. A biopsy of calf muscle reveals marked variation in size and shape of muscle fibers, with foci of muscle fiber necrosis, myophagocytosis, regenerating fibers, and fibrosis. Molecular diagnostic assays performed on muscle biopsy from the patient would show alterations in the length of the primary transcript for which muscle-associated protein?

Dystrophin. ***Dystrophin*** - The clinical features, including muscle weakness, calf muscle hypertrophy, and elevated **creatine kinase**, indicate a muscular dystrophy, most characteristically associated with **dystrophin** deficiency [1]. - **Muscle biopsy results** showing variation in muscle fiber size and necrosis further support the diagnosis of **Duchenne muscular dystrophy**, where dystrophin mutations are commonly identified [1]. *Desmin* - Although desmin is a muscle protein, it is primarily involved in **muscle fiber structure** and not directly associated with the symptoms or findings noted in this case. - Conditions linked to desmin abnormalities usually involve **myofibrillar myopathies**, which present differently than the scenario described here. *Glycogen phosphorylase* - Glycogen phosphorylase is crucial in **glycogen metabolism**, and its deficiency typically leads to metabolic myopathies presenting with **exercise intolerance** rather than the distinct symptoms of muscle necrosis seen here. - The muscle pathology observed (necrosis and regeneration) does not correlate with typical presentations seen in glycogen storage diseases. *Creatine kinase* - While creatine kinase levels are elevated in many muscle disorders, including dystrophies, it is not a structural protein and thus does not fit the question's focus on **primary transcript alterations** [2]. - Measuring creatine kinase assists in diagnosing muscle damage but does not indicate a molecular defect like **dystrophin**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1244-1245. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1245-1246.

Q: What is the gene fusion associated with Ewing's sarcoma?

EWS-FLI1. ***EWS-FLI1*** * This is the **most common and characteristic gene fusion** found in Ewing's sarcoma, occurring in about 85% of cases. * The fusion involves the **Ewing sarcoma RNA-binding protein 1 (EWSR1)** gene on chromosome 22 and the **Friend leukemia integration 1 transcription factor (FLI1)** gene on chromosome 11. *PAX3* * **PAX3** gene fusions, particularly **PAX3-FOXO1**, are associated with **alveolar rhabdomyosarcoma**, a different type of soft tissue sarcoma. * While both are pediatric tumors, their genetic drivers and typical histologies differ significantly from Ewing's sarcoma. *FUS-CHOP* * The **FUS-CHOP (DDIT3)** gene fusion is characteristic of **myxoid liposarcoma**, a distinct type of adipocytic tumor. * This fusion involves the **FUS RNA binding protein (FUS)** gene and the **DNA damage inducible transcript 3 (DDIT3)** gene. *EWS-ATF1* * The **EWS-ATF1** gene fusion is a molecular hallmark of **clear cell sarcoma** (also known as malignant melanoma of soft parts). * This fusion involves the **EWSR1** gene and the **activating transcription factor 1 (ATF1)** gene, leading to distinct biological and clinical features compared to Ewing's sarcoma.

Q: Osteosclerosis is a feature of which of the following conditions?

Osteopetrosis. ***Osteopetrosis*** - This condition is characterized by **diffuse, generalized osteosclerosis** due to defective osteoclast function [1]. - Impaired bone resorption results in **uniformly increased bone density** throughout the skeleton, creating "marble bone" appearance [1]. - This is the **classic cause of generalized osteosclerosis** [1]. *Rickets* - Rickets is caused by **vitamin D deficiency** leading to **impaired bone mineralization** in children. - Results in **bone softening (osteomalacia)** and **decreased density**, the opposite of osteosclerosis. *Hyperparathyroidism* - Causes **increased bone resorption** due to elevated parathyroid hormone levels [2]. - Leads to **osteopenia** or **osteoporosis** (decreased bone density), not osteosclerosis [2]. *Paget's Disease* - Characterized by **disorganized bone remodeling** with three phases: lytic, mixed, and sclerotic. - Can show **focal or regional osteosclerosis** in affected bones (especially in late sclerotic phase). - However, unlike osteopetrosis, it causes **localized rather than diffuse** sclerosis, with **disorganized architecture** (cotton wool appearance), not uniform increased density. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1188-1189. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, p. 1194.

Q: All of the following are diaphyseal tumors except:

Aneurysmal bone cyst. ***Aneurysmal bone cyst*** - This is primarily a **metaphyseal lesion**, though it can extend into the diaphysis or epiphysis [1]. - While it can occur in various bones, its predilection for the metaphysis distinguishes it from strictly diaphyseal tumors [1]. *Ewing's sarcoma* - This highly aggressive tumor characteristically arises in the **diaphysis** of long bones, particularly the femur, tibia, and humerus. - It classically presents with an **'onion-skin' appearance** on plain radiographs due to periosteal reaction. *Histiocytosis* - **Langerhans cell histiocytosis** commonly affects the **diaphysis** of long bones and flat bones like the skull. - It can manifest as lytic lesions within the diaphysis, often with surrounding sclerosis. *Fibrosarcoma* - This is a rare malignant tumor that can arise in the **diaphysis** of long bones. - It is characterized by the production of **collagen fibers** by malignant spindle cells. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1206-1208.

Q: Generalized thickening of cortical and cancellous bones is seen in

Osteopetrosis. ***Infantile hyperostosis*** - Characterized by **generalized thickening of both cortical and cancellous bones**, typically seen in infants. - It involves **increased bone density** and can lead to various complications including pain and deformities. *Paget's disease* - Primarily affects **older adults**, leading to **disorganized bone remodeling** rather than generalized thickening. - It often presents with **localized bone enlargement** and pain, not generalized changes in infants. *Osteopetrosis* - Features **abnormally dense bones**, but typically involves **failure of bone resorption** rather than generalized thickening [1]. - While presenting with increased bone mass, it is associated with **pathological fractures** and related complications. *Osteogenesis imperfecta* - Characterized by **brittle bones** due to defective collagen synthesis rather than thickening of bones. - Patients typically experience **frequent fractures** and **blue sclera**, which are not features of generalized thickening. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1188-1189.

Q: A 13-year-old boy, previously healthy, presents with a 1-month history of right leg pain, without trauma or recent illness. Physical examination reveals warmth, tenderness, and increased circumference of the right thigh compared to the left. His temperature is 39°C. A radiograph shows a 6-cm expansile mass in the diaphyseal region of the right lower femur, extending into soft tissue and covered by reactive bone. Microscopic examination of the mass biopsy reveals sheets of primitive cells with small, uniform nuclei and scant cytoplasm. Karyotypic analysis shows a t(11;22) translocation. What is the most likely diagnosis?

Ewing sarcoma. ***Ewing sarcoma*** - The patient's age (13-year-old), symptoms (bone pain, systemic fever), **diaphyseal location** of the tumor, and especially the characteristic histological finding of **small, uniform cells** (small round blue cell tumor) with **scant cytoplasm** point towards Ewing sarcoma. - The presence of **t(11;22)(q24;q12) translocation** resulting in the **EWSR1-FLI1 fusion gene** is a definitive diagnostic marker for Ewing sarcoma (present in ~85% of cases), distinguishing it from other bone tumors. *Chondrosarcoma* - This tumor typically affects older adults (>40 years) and arises from cartilage, showing cartilaginous matrix on histology. - It lacks the specific t(11;22) translocation seen in this patient. *Giant cell tumor* - Giant cell tumors typically occur in young adults (20-40 years) and are usually found in the **epiphyseal and metaphyseal regions** of long bones. - Histologically, they contain numerous **multinucleated giant cells** interspersed with mononuclear stromal cells, not sheets of primitive cells. *Metastatic carcinoma* - Metastatic carcinoma to bone is rare in children and usually occurs in older adults with a known primary cancer. - The histology of "sheets of primitive cells with small, uniform nuclei and scant cytoplasm" is not typical for metastatic carcinoma.

Q: Which of the following is a benign tumor?

Fibromatosis. ***Fibromatosis*** - Fibromatosis is classified as a **benign fibrous tumor** [1][3], meaning it does not have the potential to metastasize. - It involves **proliferation of fibroblasts** [1] and is primarily characterized by local invasiveness rather than malignancy. *Askin's tumor* - Also known as **primitive neuroectodermal tumor (PNET)**, it is recognized as a **malignant tumor** commonly affecting the chest wall. - Associated with strong **aggressive behavior** and metastatic potential, particularly in pediatric populations. *Liposarcoma* - Liposarcoma is a malignant tumor arising from **adipose tissue** [2][3], exhibiting aggressive growth and potential for metastasis. - It is classified as a **soft tissue sarcoma** [2], with various subtypes depending on histological features [2]. *Chloroma* - Chloroma, or **myeloid sarcoma**, is a malignant tumor of **myeloid lineage cells** typically associated with acute myeloid leukemia (AML). - Characterized by the **extramedullary infiltration** of myeloid cells, leading to clinical aggressiveness. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1223-1224. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1222-1223. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, p. 1222.

Q: Ewing's sarcoma arises from which of the following tissues?

Mesenchymal stem cells. ***Mesenchymal stem cells*** - **Ewing's sarcoma** arises from **mesenchymal stem cells (MSCs)**, which are multipotent stromal cells of mesodermal origin. - The characteristic **t(11;22)(q24;q12) translocation** results in the **EWS-FLI1 fusion gene**, which transforms mesenchymal stem cells into the malignant small round blue cells characteristic of Ewing's sarcoma. - This mesodermal/mesenchymal origin explains its predominant occurrence in **bone and soft tissues**. *Endothelial cells* - Tumors arising from **endothelial cells** are **vascular tumors** such as hemangiomas or angiosarcomas. - These have distinct histological features with vascular channel formation, unlike the solid sheets of small round blue cells seen in Ewing's sarcoma. *Osteocytes* - Tumors derived from **osteocytes** or osteoblastic cells are **bone-forming tumors**, such as osteosarcoma. - **Osteosarcoma** produces osteoid and has a distinct histology and genetic profile from Ewing's sarcoma. *Primitive neuroectodermal cells* - Historically, Ewing's sarcoma was thought to arise from **primitive neuroectodermal cells (PNETs)** due to occasional neural marker expression. - However, modern molecular studies have established that Ewing's sarcoma originates from **mesenchymal stem cells**, not neuroectodermal cells. - The term "PNET" in this context is now considered **outdated**.

Q: What is the typical chromosomal complement in primary chondrosarcoma cells?

Diploid (46 chromosomes). ***Diploid (46 chromosomes)*** - Primary **chondrosarcomas** arise from normal cartilage cells and typically maintain a **diploid chromosomal number (46 chromosomes)** [1]. - While primary chondrosarcomas may develop complex karyotypic abnormalities including structural rearrangements, they retain the diploid complement (46,XX in females or 46,XY in males) [1]. - This distinguishes them from germ cell tumors or other neoplasms that might have different ploidy states [2]. *Haploid (23 chromosomes)* - A **haploid state** (23 chromosomes) is characteristic of **germ cells** (sperm and ova), not somatic cells [2]. - Somatic tumors like chondrosarcomas are derived from diploid cells and do not exhibit haploidy. *Triploid (69 chromosomes)* - **Triploidy** involves three complete sets of chromosomes and is typically seen in certain **molar pregnancies** or non-viable embryos. - This is not a feature of chondrosarcomas or other bone tumors. *Tetraploid (92 chromosomes)* - **Tetraploidy** can occur in some cancers as a result of genome doubling events. - While some malignancies may show tetraploid populations, primary chondrosarcomas typically maintain a **diploid** state with structural chromosomal abnormalities rather than whole genome duplication [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1204-1205. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lower Urinary Tract and Male Genital System, pp. 979-980.

Q: Which of the following soft tissue sarcomas does not typically have a propensity for lymphatic spread?

Malignant Peripheral Nerve Sheath Tumor (MPNST). ***Malignant Peripheral Nerve Sheath Tumor (MPNST)*** - **MPNSTs**, like most soft tissue sarcomas, primarily metastasize hematogenously to the lungs [3], and **lymphatic spread is rare** [1]. - Their origin from peripheral nerves explains their tendency for local invasion and distant blood-borne metastases rather than lymphatic involvement [1]. *Synovial sarcoma* - **Synovial sarcoma** is one of the soft tissue sarcomas that has a **higher propensity for lymphatic spread** compared to many others [2]. - While hematogenous spread is also common, clinicians should always assess regional lymph nodes when evaluating this type of tumor. *Rhabdomyosarcoma* - **Rhabdomyosarcoma** is a highly aggressive tumor, particularly in children, and frequently shows **lymphatic metastasis**, especially in parameningeal, genitourinary, and extremity sites. - Due to its high metastatic potential, regional lymph node involvement is a crucial prognostic factor. *Epithelioid sarcoma* - **Epithelioid sarcoma** is known for its **propensity for both regional lymphatic spread** and local recurrence. - The pattern of spread often mimics carcinomas, making thorough regional lymph node evaluation essential. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1250-1251. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1225-1226. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 282.

Question 1

A 4-year-old boy is brought to the physician by his parents due to frequent falls, inability to jump, and easy fatigue. Physical examination reveals weakness in the pelvic and shoulder girdles, as well as enlargement of the child's calf muscles. The serum level of creatine kinase is elevated. A biopsy of calf muscle reveals marked variation in size and shape of muscle fibers, with foci of muscle fiber necrosis, myophagocytosis, regenerating fibers, and fibrosis. Molecular diagnostic assays performed on muscle biopsy from the patient would show alterations in the length of the primary transcript for which muscle-associated protein?

Accepted Answer

Dystrophin

Answer

Creatine kinase

Answer

Desmin

Answer

Glycogen phosphorylase

Question 2

What is the gene fusion associated with Ewing's sarcoma?

Accepted Answer

EWS-FLI1

Answer

FUS-CHOP

Answer

EWS-ATF1

Answer

PAX3-FOXO1

Question 3

Osteosclerosis is a feature of which of the following conditions?

Accepted Answer

Osteopetrosis

Answer

Hyperparathyroidism

Answer

Paget's Disease

Answer

Rickets

Question 4

All of the following are diaphyseal tumors except:

Accepted Answer

Aneurysmal bone cyst

Answer

Histiocytosis

Answer

Fibrosarcoma

Answer

Ewing's sarcoma

Question 5

Generalized thickening of cortical and cancellous bones is seen in

Accepted Answer

Osteopetrosis

Answer

Infantile hyperostosis

Answer

Paget's disease

Answer

Osteogenesis imperfecta

Question 6

A 13-year-old boy, previously healthy, presents with a 1-month history of right leg pain, without trauma or recent illness. Physical examination reveals warmth, tenderness, and increased circumference of the right thigh compared to the left. His temperature is 39°C. A radiograph shows a 6-cm expansile mass in the diaphyseal region of the right lower femur, extending into soft tissue and covered by reactive bone. Microscopic examination of the mass biopsy reveals sheets of primitive cells with small, uniform nuclei and scant cytoplasm. Karyotypic analysis shows a t(11;22) translocation. What is the most likely diagnosis?

Accepted Answer

Ewing sarcoma

Answer

Chondrosarcoma

Answer

Giant cell tumor

Answer

Metastatic carcinoma

Question 7

Which of the following is a benign tumor?

Accepted Answer

Fibromatosis

Answer

Liposarcoma

Answer

Askin's tumor

Answer

Chloroma

Question 8

Ewing's sarcoma arises from which of the following tissues?

Accepted Answer

Mesenchymal stem cells

Answer

Endothelial cells

Answer

Osteocytes

Answer

Primitive neuroectodermal cells

Question 9

What is the typical chromosomal complement in primary chondrosarcoma cells?

Accepted Answer

Diploid (46 chromosomes)

Answer

Triploid (69 chromosomes)

Answer

Haploid (23 chromosomes)

Answer

Tetraploid (92 chromosomes)

Question 10

Which of the following soft tissue sarcomas does not typically have a propensity for lymphatic spread?

Accepted Answer

Malignant Peripheral Nerve Sheath Tumor (MPNST)

Answer

Rhabdomyosarcoma

Answer

Synovial sarcoma

Answer

Epithelioid sarcoma

Bone and Soft Tissue Pathology — MCQs

Bone and Soft Tissue Pathology — MCQs

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