Tumor vascularization and histopathologic regression of soft tissue sarcomas treated with isolated limb perfusion with TNF-α and melphalan.

BACKGROUND: Isolated limb perfusion (TM-ILP) achieves high response rates in soft tissue sarcomas (STS). Some tumors show an insufficient association between radiological and pathological response. We investigated STS after TM-ILP with a primary emphasis on histologic regression patterns. METHODS: In 53 patients with STS, TM-ILP with subsequent tumor resection was performed. Regression was assessed by the Salzer-Kuntschik regression scale. Microvessel density (MVD) of primary biopsies of 37 patients was determined by immunohistochemistry. Tumor regression was correlated with MVD of primary biopsies and other clinico-pathological parameters. RESULTS: Regression presented mainly as necrosis or fibrosis/sclerosis upon histopathology. MFH, leiomyosarcoma, or clear cell sarcoma (CCS) responded well; whereas liposarcomas, synovial sarcomas, or MPNST were poor responders. MFH often had abundant necrosis; while other STS mainly presented with fibrosis/sclerosis. MVD had no influence on regression grade but modulated histologic regression patterns. Excellent regression demonstrated a trend toward an association with improved survival and local control. CONCLUSION: TM-ILP yielded high response rates in STS. Regression after TM-ILP exhibits MVD-dependent histopathologic patterns and variable efficacy in different sarcoma types. Complete regression seems to be a favorable prognostic factor. A concerted consideration of histopathology and clinical findings may contribute to a better clinical assessment of regression after TM-ILP.

Evaluation of 47 soft tissue sarcoma resection specimens after isolated limb perfusion with TNF-alpha and melphalan: histologically characterized improved margins correlate with absence of recurrences.

BACKGROUND: Isolated limb perfusion (TM-ILP) is an effective limb-sparing treatment for primarily nonresectable soft tissue sarcomas (STS). Surgical margins of STS after ILP were yet not systematically studied. METHODS: In 47 patients with nonresectable STS, TM-ILP with subsequent tumor resection was performed. Surgical margins were systematically analyzed by light microscopy using the TNM and the Enneking classification. Furthermore, margins were analyzed for tumor regression in terms of improved resectability. Results were correlated with clinical and pathological parameters. RESULTS: Of 47 STS, 44 were classified as high-grade (93.6%) with a median tumor size of 10.0 cm. Primary limb-salvage rate was 85.1%. According to TNM resection margins were complete in 70.2% (R0) and incomplete in 29.8% (R1=21.3%, R2=8.5%). According to Enneking, 27.7% intralesional, 42.6% marginal, 21.3% wide, 2.1% radical, and 6.4% unclassifiable margins were found. Prior surgery and/or radiotherapy significantly decreased margin quality. Ten patients with incomplete resection (three intralesional, seven marginal) had no viable tumor at the plane of dissection, which was designated as "improved margins." Whereas those patients remained relapse free, five patients with viable tumor (not improved margins) at the resection margin had local recurrences. Poor margins were associated with local and distant recurrences and limited disease-specific survival. CONCLUSION: TM-ILP is effective for achieving limb salvage. Histopathology of surgical margins demonstrates cases with so-called "improved margins" after TM-ILP, which are related to a better outcome even in intralesionally resected tumors. Improvement of margins should be further evaluated as a potential relevant prognostic parameter.