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

J Surg Oncol. 2011 Apr;103(5):371-9. doi: 10.1002/jso.21724.


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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Chemotherapy, Cancer, Regional Perfusion*
  • Extremities*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Melphalan / administration & dosage*
  • Middle Aged
  • Neoplasm Recurrence, Local / blood supply
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Neovascularization, Pathologic / drug therapy*
  • Sarcoma / blood supply*
  • Sarcoma / pathology
  • Survival Rate
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / administration & dosage*
  • Young Adult


  • Antineoplastic Agents, Alkylating
  • Tumor Necrosis Factor-alpha
  • Melphalan