Soft Tissue Sarcoma — Enneking

Soft tissue sarcomas (STS) are a heterogeneous group of malignant mesenchymal tumours arising in connective tissues outside the skeleton. They account for approximately 1% of adult malignancies but carry significant morbidity and mortality. The Enneking staging system provides the framework for surgical planning, defining the goal of surgery and the required margins based on tumour grade and compartmental extent.

• Incidence: approximately 3–5 per 100,000 population; approximately 3,700 new cases per year in the UK; approximately 13,000 per year in the USA
• Most common histological subtypes: undifferentiated pleomorphic sarcoma (UPS/MFH) most common in adults; liposarcoma; leiomyosarcoma; synovial sarcoma (young adults, near joints); rhabdomyosarcoma (children)
• Most common sites: lower limb (45%), upper limb (15%), trunk (15%), retroperitoneum (15%)
• The "lump rule" — refer urgently any soft tissue lump that is: >5 cm, deep to fascia, increasing in size, or recurrent after previous excision; do NOT excise an undiagnosed soft tissue lump without appropriate imaging and staging — inadvertent excision of a sarcoma without adequate margins is the most common surgical error in STS management
• Metastasis: haematogenous predominantly to lungs (90% of metastases); lymph node metastases uncommon (<5%) except epithelioid sarcoma, rhabdomyosarcoma, and synovial sarcoma

The Enneking (Musculoskeletal Tumour Society, MSTS) staging system classifies sarcomas based on grade (G), local extent (T), and metastasis (M). It is widely used for both bone and soft tissue sarcomas.

• Intracompartmental (T1): tumour confined within one anatomical compartment (e.g., anterior thigh compartment, posterior leg compartment); extracompartmental (T2): tumour has crossed compartmental boundaries — invades adjacent compartment, neurovascular structures, or is in an extracompartmental site (popliteal fossa, groin, antecubital fossa, axilla)
• Compartmental boundaries: fascial planes, cortical bone, and articular surfaces act as natural barriers to tumour spread; once crossed, surgical planning becomes more complex

The Enneking surgical margin concept defines the relationship between the surgical cut and the tumour and its reactive zone. The required margin is determined by tumour grade and stage.

• The most common surgical error in STS is inadvertent marginal excision — the "oops" resection; a benign-appearing lump is excised without imaging and turns out to be a sarcoma; the excision invariably goes through the reactive zone; re-excision of the tumour bed ± radiotherapy is required; local recurrence and potentially worse oncological outcome results
• Limb-salvage surgery with wide margins + adjuvant radiotherapy is now equivalent to amputation in local control for most extremity STS — amputation is now reserved for cases where wide margins cannot be achieved without sacrifice of critical neurovascular structures

• Biopsy must be performed by or in close consultation with the treating sarcoma surgeon — the biopsy tract is contaminated and must be excised en-bloc with the tumour at definitive surgery; incorrect biopsy placement can necessitate amputation or wider resection
• Core needle biopsy: preferred technique — multiple cores from representative area; longitudinal biopsy incision (never transverse); direct approach through one compartment only; avoid NV bundles; avoid joint contamination; haemostasis critical to prevent haematoma tracking
• Open biopsy: used when core needle is non-diagnostic; incisional (wedge) or excisional; incisional preferred for large tumours; longitudinal incision; minimal flaps; drain in line with incision (drain exit contaminated); send fresh tissue for histology, cytogenetics, and cultures
• Excisional biopsy: acceptable only for lesions <3 cm and superficial — in larger lesions risks inadequate margins for a sarcoma
• Never perform open biopsy in a referring centre and then refer to sarcoma centre — this contaminates tissue planes; refer all suspicious lumps before any biopsy

• Radiotherapy: reduces local recurrence after wide excision for high-grade STS; pre-operative (neoadjuvant) or post-operative; pre-operative RT has smaller field and lower dose (50 Gy) but higher wound complication rate; post-operative RT higher dose (60–66 Gy) but lower wound complications; both approaches equivalent for local control; surgeon and radiation oncologist preference guides choice
• Chemotherapy: role more limited in STS than in bone sarcomas; doxorubicin + ifosfamide is the standard first-line regimen for advanced/metastatic high-grade STS; neoadjuvant chemotherapy for selected high-grade, large, deep tumours; subtype-specific chemotherapy — trabectedin for myxoid liposarcoma; gemcitabine/docetaxel for leiomyosarcoma and UPS
• Isolated limb perfusion (ILP): for locally advanced unresectable limb STS; high-dose melphalan ± TNF-α delivered intra-arterially under tourniquet; achieves tumour reduction in approximately 80%; enables limb-salvage surgery in selected cases

• Synovial sarcoma: despite the name, does NOT arise from synovium — arises from primitive mesenchymal cells near joints; characterised by t(X;18) translocation (SYT-SSX fusion gene); biphasic (epithelial + spindle cell) or monophasic; young adults (15–35 years); lower extremity near knee most common; calcification in 30%; treatment: wide excision + radiotherapy ± chemotherapy; 5-year survival approximately 50–60%
• Retroperitoneal sarcoma: most commonly liposarcoma or leiomyosarcoma; presents large and often unresectable; complete resection (R0) is the only curative treatment but achieved in only 50–70%; high local recurrence rate; CT-guided biopsy before surgery; multivisceral resection often required
• Rhabdomyosarcoma in children: most common STS in children; head/neck (40%), genitourinary (25%), extremity (20%); three subtypes: embryonal (best prognosis), alveolar (worst, PAX3/7-FOXO1 fusion), pleomorphic (adults); multimodal treatment: chemotherapy (vincristine, actinomycin D, cyclophosphamide — VAC regimen) + surgery ± radiotherapy
• Recurrence surveillance: high-grade STS — chest CT every 3–4 months for first 2–3 years (lung metastases), then every 6 months; local surveillance with MRI of primary site every 6 months for 5 years; 5-year survival for localised high-grade STS approximately 50–60%; for metastatic disease approximately 15–20%

• Refer any lump: >5 cm, deep to fascia, growing, or recurrent — do NOT excise without staging imaging
• Enneking staging: Grade (G1 low / G2 high) × Site (T1 intracompartmental / T2 extracompartmental) × Metastasis (M0/M1); Stage III = any + metastases
• Wide margin = standard for high-grade STS = cuff of normal tissue around reactive zone; marginal = shell out through pseudocapsule = unacceptable for sarcoma
• Biopsy tract = contaminated = must be excised with tumour; longitudinal incision; one-compartment approach; no transverse incisions
• Inadvertent marginal excision ("oops" sarcoma): most common error; re-excision + radiotherapy required; may worsen outcome
• Limb salvage + wide margin + RT = equivalent to amputation for local control; amputation reserved for unresectable NV involvement
• Metastasis: lungs (90%); chest CT every 3–4 months for surveillance; lymph nodes uncommon except synovial sarcoma, rhabdomyosarcoma, epithelioid sarcoma
• Synovial sarcoma: NOT from synovium; t(X;18); young adults near knee; calcification 30%; biphasic or monophasic histology
• Pre-op RT: smaller field, 50 Gy, higher wound complication; post-op RT: larger field, 60–66 Gy, lower wound complication; equivalent local control
• ILP (isolated limb perfusion): melphalan ± TNF for unresectable limb STS; 80% response rate; enables limb salvage