SRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular Tumors

Am J Surg Pathol. 2020 Dec;44(12):1725-1735. doi: 10.1097/PAS.0000000000001546.

Abstract

Pericytic tumors encompass several entities sharing morphologic and immunohistochemical features. A subset of perivascular myoid tumors associated with the SRF-RELA fusion gene was previously described. Herein, we report a series of 13 tumors belonging to this group, in which we have identified new fusion genes by RNA-sequencing, thus expanding the molecular spectrum of this entity. All patients except 1 were children and infants. The tumors, frequently located in the head (n=8), had a mean size of 38 mm (range 10 to 150 mm) and were mostly (n=9) well-circumscribed. Exploration of the follow-up data (ranging from 3 to 68 mo) confirmed the benign behavior of these tumors. These neoplasms presented a spectrum of morphologies, ranging from perivascular patterns to myoid appearance. Tumor cells presented mitotic figures but without marked atypia. Some of these tumors could mimic sarcoma. The immunohistochemical profiles confirmed a pericytic differentiation with the expression of the smooth muscle actin and the h-caldesmon, as well as the frequent positivity for pan-cytokeratin. The molecular analysis identified the expected SRF-RELA fusion gene, in addition to other genetic alterations, all involving SRF fused to CITED1, CITED2, NFKBIE, or NCOA2. The detection of SRF-NCOA2 fusions in spindle cell rhabdomyosarcoma of the infant has previously been described, representing a risk of misdiagnosis, although the cases reported herein did not express MyoD1. Finally, clustering analyses confirmed that this group of SRF-fused perivascular myoid tumors forms a distinct entity, different from other perivascular tumors, spindle cell rhabdomyosarcomas of the infant, and smooth muscle tumors.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Apoptosis Regulatory Proteins / genetics
  • Biomarkers, Tumor / genetics*
  • Child
  • Child, Preschool
  • England
  • Female
  • France
  • Gene Fusion*
  • Humans
  • I-kappa B Proteins / genetics
  • Male
  • Neoplasms, Connective and Soft Tissue / genetics*
  • Neoplasms, Connective and Soft Tissue / pathology
  • Nuclear Receptor Coactivator 2 / genetics
  • Proto-Oncogene Proteins / genetics
  • Repressor Proteins / genetics
  • Serum Response Factor / genetics*
  • Trans-Activators / genetics
  • Transcription Factor RelA / genetics*

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • CITED1 protein, human
  • CITED2 protein, human
  • I-kappa B Proteins
  • NCOA2 protein, human
  • NFKBIE protein, human
  • Nuclear Receptor Coactivator 2
  • Proto-Oncogene Proteins
  • RELA protein, human
  • Repressor Proteins
  • SRF protein, human
  • Serum Response Factor
  • Trans-Activators
  • Transcription Factor RelA