Leiomyosarcoma of Soft Tissue

Do not confuse soft tissue leiomyosarcoma with gastrointestinal stromal tumour (GIST). Historically many gut "leiomyosarcomas" were reclassified as GISTs once KIT/CD117 and DOG1 testing became available. True leiomyosarcoma is KIT-negative, is driven by smooth-muscle biology rather than KIT/PDGFRA mutations, and does not respond to imatinib. Modern leiomyosarcoma series deliberately exclude GISTs.

The total FNCLCC score (differentiation plus mitotic count plus necrosis) maps to grade 1, 2 or 3. High grade (grade 3) is independently associated with distant recurrence and death. In leiomyosarcoma specifically, grade and size are the dominant predictors of disease-specific survival.

Leiomyosarcoma can recur late - distant or local recurrence beyond 5 years is well described, particularly for abdominal and retroperitoneal tumours. A written long-term surveillance plan is essential.

In primary leiomyosarcoma, multivariate analysis shows that grade and size are the dominant independent predictors of disease-specific survival and distant recurrence, while margin status drives local recurrence. Although retroperitoneal tumours do worse than extremity tumours, much of that difference is explained by their larger size and the difficulty of obtaining clear margins.

Q: Which immunohistochemical profile confirms leiomyosarcoma? A: Positive for smooth-muscle markers - desmin, smooth muscle actin (SMA) and h-caldesmon - with characteristic spindle cells showing blunt-ended (cigar-shaped) nuclei. KIT/CD117 is negative, which helps exclude GIST.

Q: What are the dominant independent predictors of survival in primary soft tissue leiomyosarcoma? A: FNCLCC grade and tumour size. Margin status is the key driver of local recurrence. Retroperitoneal site is associated with worse outcome largely because of larger size and margin difficulty.

Q: Is adjuvant chemotherapy standard after resection of localised leiomyosarcoma? A: No. The EORTC 62931 randomised trial of doxorubicin plus ifosfamide showed no relapse-free or overall survival benefit. Chemotherapy is reserved for advanced disease or individualised high-risk cases.

Q: How does soft tissue leiomyosarcoma differ from GIST? A: Leiomyosarcoma is a true smooth-muscle tumour that is KIT-negative and does NOT respond to imatinib. GIST is KIT/DOG1 positive and is treated with imatinib. Many old gut "leiomyosarcomas" were reclassified as GISTs.

Q: What are the dominant metastatic sites in leiomyosarcoma? A: Lung for extremity tumours; liver is also important for retroperitoneal and vascular tumours. Spread is predominantly haematogenous and lymph-node metastasis is uncommon.

Every major society agrees on three points regardless of region: any suspicious deep or enlarging soft tissue mass should be referred to a specialist sarcoma centre before biopsy, diagnosis should be made by planned core biopsy with immunohistochemistry, and definitive management should be set by a multidisciplinary sarcoma team. The main areas of disagreement are the thresholds for radiotherapy and for any systemic therapy.