Expanding the spectrum of malignant change in schwannomas: epithelioid malignant change, epithelioid malignant peripheral nerve sheath tumor, and epithelioid angiosarcoma: a study of 17 cases

Am J Surg Pathol. 2001 Jan;25(1):13-25. doi: 10.1097/00000478-200101000-00002.

Abstract

Schwannomas (neurilemmomas) rarely undergo malignant change, most often in the form of either malignant peripheral nerve sheath tumor (MPNST) or angiosarcoma. We characterize the clinical features and the histopathologic spectrum of 17 schwannomas with evidence of malignant change. The study group comprised 7 males and 10 females with an age range of 16 to 76 years, (median, 40 yrs). None of the patients had neurofibromatosis. Lesions ranged in size from 0.6 to 10.5 cm (median, 4.0 cm) and arose mainly in the limbs/limb girdles (7 cases) or head and neck region (7 cases). All tumors contained areas of conventional benign schwannoma. Four cases of pure epithelioid malignant peripheral nerve sheath tumor (EMPNST) were identified, three of which showed immunopositivity for S-100 protein. Four angiosarcomas were identified, predominantly epithelioid-type. Ten schwannomas had an appearance that we have designated epithelioid malignant change (EMC) and, in one of these, EMC coexisted with EMPNST. Large epithelioid cells with abundant eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli (morphologically similar to cells of EMPNST) were distributed throughout the schwannoma--singly, in clusters, and in one case a microscopic nodule of such cells was also present. These large epithelioid cells were strongly positive for S-100 protein. Although follow-up data so far are limited, 1 of 5 patients with EMC in whom meaningful follow up was available developed repeated local recurrence (median follow up, 21 mos), one patient each with EMPNST and angiosarcoma died of local and metastatic disease. Pure EMPNST is rare; however, we confirm the tendency of MPNST to show epithelioid cytomorphology when arising in a benign schwannoma. We also confirm the distinctive (albeit infrequent) tendency of angiosarcoma to arise in schwannomas. We describe EMC in schwannomas and suggest that this represents a putative precursor lesion of EMPNST. At this time, we do not have an explanation for the tendency of schwannomas to show epithelioid cytomorphology when they undergo malignant change.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Follow-Up Studies
  • Hemangiosarcoma / chemistry
  • Hemangiosarcoma / pathology
  • Humans
  • Ki-67 Antigen / analysis
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Nerve Sheath Neoplasms / chemistry
  • Nerve Sheath Neoplasms / pathology
  • Neurilemmoma / pathology*
  • S100 Proteins / analysis
  • Tumor Suppressor Protein p53 / analysis

Substances

  • Ki-67 Antigen
  • Neoplasm Proteins
  • S100 Proteins
  • Tumor Suppressor Protein p53