Epithelioid and spindle cell rhabdomyosarcoma with FUS-TFCP2 or EWSR1-TFCP2 fusion: report of two cases

Virchows Arch. 2020 Nov;477(5):725-732. doi: 10.1007/s00428-020-02870-0. Epub 2020 Jun 19.

Abstract

The WHO Classification of Tumors of Soft Tissue and Bone divides rhabdomyosarcoma (RMS) into alveolar, embryonal, pleomorphic, and spindle cell/sclerosing types. Advances in molecular diagnostics have allowed for further refinement of RMS classification including the identification of new subtypes. Very rare RMS with epithelioid and spindle cell morphology, female predominance, marked osseous predilection, ALK expression, EWSR1/FUS-TFCP2 gene fusions, and highly aggressive clinical behavior have recently been recognized with only 23 cases reported in the English language literature. Herein, we report two additional cases with detailed clinicopathologic description and molecular confirmation. In brief, two young women presented each with a primary bone tumor-one with a frontal bone tumor and another with an osseous pelvic tumor. Both tumors showed epithelioid to spindle cell morphology, ALK expression, and EWSR1/FUS-TFCP2 gene fusions. Both patients died of disease less than 17 months from diagnosis despite administration of multiple lines of aggressive treatment. In addition, we review the literature and discuss differential diagnostic and potential treatment considerations.

Keywords: Bone; EWSR1-TFCP2; Epithelioid and spindle cell rhabdomyosarcoma; FUS-TFCP2; Rhabdomyosarcoma; TFCP2.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics*
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Epithelioid Cells / pathology
  • Fatal Outcome
  • Female
  • Frontal Bone / pathology
  • Gene Fusion*
  • Genetic Predisposition to Disease
  • Humans
  • Pelvic Neoplasms / diagnostic imaging
  • Pelvic Neoplasms / genetics*
  • Pelvic Neoplasms / pathology
  • Pelvic Neoplasms / therapy
  • Phenotype
  • RNA-Binding Protein EWS / genetics*
  • RNA-Binding Protein FUS / genetics*
  • Rhabdomyosarcoma / diagnostic imaging
  • Rhabdomyosarcoma / genetics*
  • Rhabdomyosarcoma / secondary
  • Rhabdomyosarcoma / therapy
  • Skull Neoplasms / diagnostic imaging
  • Skull Neoplasms / genetics*
  • Skull Neoplasms / pathology
  • Skull Neoplasms / therapy
  • Transcription Factors / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • EWSR1 protein, human
  • FUS protein, human
  • RNA-Binding Protein EWS
  • RNA-Binding Protein FUS
  • TFCP2 protein, human
  • Transcription Factors