Ectomesenchymal Chondromyxoid Tumor: A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions

Am J Surg Pathol. 2018 Oct;42(10):1297-1305. doi: 10.1097/PAS.0000000000001096.

Abstract

Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2 fusion product was identified in 19 tumors (90%), a single tumor (5%) had an EWSR1-CREM fusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2 fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Adolescent
  • Adult
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • DNA-Binding Proteins / genetics*
  • Desmin / analysis
  • Female
  • Gene Fusion*
  • Genetic Predisposition to Disease
  • Glial Fibrillary Acidic Protein / analysis
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Keratins / analysis
  • Male
  • Middle Aged
  • Neoplasms, Connective and Soft Tissue / chemistry
  • Neoplasms, Connective and Soft Tissue / genetics*
  • Neoplasms, Connective and Soft Tissue / pathology
  • Phenotype
  • Retrospective Studies
  • S100 Proteins / analysis
  • Sequence Analysis, RNA
  • Tongue Neoplasms / chemistry
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / pathology
  • Transcription Factors / genetics*
  • Young Adult

Substances

  • Actins
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Desmin
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • MRTFB protein, human
  • RREB1 protein, human
  • S100 Proteins
  • Transcription Factors
  • Keratins