Molecular Pathology of Common Musculoskeletal Disorders: Essential Insights for Radiologists

Purpose or Learning Objective: This educational poster highlights for radiologists the importance of molecular pathology in various musculoskeletal (MSK) disorders.

Methods or Background: The role of molecular pathology has been increasing during recent years. This poster focuses on the critical role of molecular pathology in understanding molecular and genetic changes in common MSK conditions, which is important knowledge for radiologists. Each method’s application and diagnostic relevance in detecting specific gene disorders in MSK tumors are summarized.

Results or Findings: The following pathologic markers, commonly used in MSK pathologies, are discussed in this poster: Mouse double minute-2 (MDM-2) amplification is primarily linked to atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLPS), as well as dedifferentiated liposarcomas (DDLPS). High MDM-2 expression in tumor cells helps distinguish atypical lipomatous tumors/well-differentiated liposarcomas and dedifferentiated liposarcomas from benign lipomas or other benign adipocytic tumors. Guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) mutations are primarily associated with fibrous dysplasia. GNAS mutations involve a somatic mutation that causes a molecular pathway dysregulation, resulting in abnormal bone development. Ubiquitin-specific protease 6 (USP6) gene rearrangements are diagnostic for nodular fasciitis and myositis ossificans, and associated with aneurysmal bone cysts. Identification of USP6 gene rearrangements serves as a diagnostic marker. Some patients might benefit from targeted treatments aimed at USP6 expression.

Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements are commonly found in Ewing’s sarcoma. Identification of these gene rearrangements using molecular techniques serves as a diagnostic marker for confirming the diagnosis of Ewing’s sarcoma. Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are identified in various tumors, including infantile fibrosarcoma and congenital mesoblastic nephroma. Tumors with NTRK fusions may respond to targeted therapies such as TRK inhibitors. These inhibitors specifically target the abnormal TRK fusion proteins, providing potential therapeutic benefits.

Conclusion: Molecular pathology is an emerging discipline for differentiating and accurate diagnoses of various benign and malignant MSK tumors. Knowledge of various molecular pathology techniques and specific markers enables radiologists to have interdisciplinary discussions with pathologists, surgeons, and oncologists for accurate classification of soft tissue and bone tumors. Moreover, molecular pathology guides treatment decisions and contributes significantly to personalized approaches in managing diverse MSK tumors and tumor-like disorders.

 

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Artikel online veröffentlicht:
22. Mai 2024