High-grade salivary gland carcinoma with the ETV6-NTRK3 gene fusion: A case report and literature review of secretory carcinoma with high-grade transformation

Pathol Int. 2021 Jun;71(6):427-434. doi: 10.1111/pin.13100. Epub 2021 Apr 13.

Abstract

Secretory carcinoma or mammary analog secretory carcinoma is an entity of salivary gland carcinoma that is characterized by the ETV6-NTRK3 gene fusion. Although it is generally considered to be a low-grade malignancy, some cases of secretory carcinoma with high-grade transformation (SCHG) have been reported. We herein describe a case of SCHG composed almost exclusively of the high-grade component. The patient presented with a growing mass in the buccal mucosa and underwent surgery. Tumor cells showing high-grade nuclear atypia were arranged in solid or cribriform nests with comedo-like necrosis. A differential diagnosis included high-grade salivary gland carcinoma, such as salivary duct carcinoma. Immunohistochemically, tumor cells were focally positive for S-100 and negative for mammaglobin and showed nuclear positivity for pan-Trk. A reverse transcription polymerase chain reaction assay showed that the tumor harbored the ETV6-NTRK3 gene fusion. A histological review of microscopic slides of the tumor did not reveal a typical secretory carcinoma component, except for a very focal area. We ultimately diagnosed this tumor as SCHG. This case underscores the importance of recognizing the histological spectrum of SCHG and the utility of pan-Trk immunohistochemistry to detect secretory carcinoma, which may be targeted by tyrosine kinase inhibitors.

Keywords: ETV6-NTRK3; high-grade transformation; pan-Trk; salivary gland carcinoma; secretory carcinoma.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis
  • Carcinoma* / diagnosis
  • Carcinoma* / pathology
  • Carcinoma, Acinar Cell
  • Diagnosis, Differential
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Oncogene Proteins, Fusion / analysis*
  • Oncogene Proteins, Fusion / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Salivary Gland Neoplasms* / diagnosis
  • Salivary Gland Neoplasms* / pathology
  • Salivary Glands / pathology

Substances

  • Biomarkers, Tumor
  • ETV6-NTRK3 fusion protein, human
  • Oncogene Proteins, Fusion
  • Protein-Tyrosine Kinases