Musculoskeletal tumours are diverse, historically classified by morphology and histology.
WHO classification is the gold standard.
Advances in molecular biology, cytogenetics, and sequencing improved diagnostic precision (e.g., EWS-FLI1 in Ewing sarcoma, USP6 rearrangement in ABC).
Tissue of Origin
Most arise from mesenchymal tissue (bone, cartilage, fibrous tissue, fat, muscle).
Some from neuroectodermal cells (nerve sheath tumours, PNET).
Others are secondary (metastatic carcinomas, hematologic malignancies).
Benign vs Malignant
Benign: No metastatic potential but may be locally aggressive (e.g., GCT, ABC).
Malignant: Sarcomas (osteosarcoma, Ewing sarcoma, chondrosarcoma, soft tissue sarcomas).
Borderline/atypical lesions exist (e.g., atypical lipomatous tumour).
Key Biological Features
Oncogenes & tumour suppressor genes: TP53, RB1, IDH mutations.
Translocations: EWS-FLI1 in Ewing’s, SYT-SSX in synovial sarcoma.
Microenvironment: Angiogenesis, immune evasion, stromal interactions.
Invasion: Matrix metalloproteinases facilitate spread.
Clinical Relevance
Guides diagnosis (histology + immunohistochemistry + molecular testing).
Determines prognosis (grading, staging systems).
Provides therapeutic targets (e.g., checkpoint inhibitors, IDH inhibitors).
Emphasises importance of biopsy strategy (always after imaging, in referral centres).
Research Focus
Integration of genomics and molecular diagnostics for accurate classification.
Development of targeted therapies for sarcomas.
Collaborative research networks (e.g., NCRI Sarcoma Clinical Studies Group in the UK).
References
WHO Classification of Soft Tissue and Bone Tumours, 2020
Rankin KS. Basic science of musculoskeletal tumours. MPorth, 2017
Hanahan D, Weinberg RA. Hallmarks of Cancer. Cell, 2011
Well differentiated liposarcoma
Myxoid liposarcoma pathology
Schwannoma pathology
