Salivary Secretory Carcinoma Harboring a Novel ALK Fusion: Expanding the Molecular Characterization of Carcinomas Beyond the ETV6 Gene

Am J Surg Pathol. 2020 Jul;44(7):962-969. doi: 10.1097/PAS.0000000000001471.

Abstract

Secretory carcinoma (SC) of the salivary glands is a low-grade carcinoma characterized by a well-defined morphology and immunohistochemical features. ETV6-NTRK3 fusions are detected in the great majority of SCs. Recently, other partners fused to ETV6 have been documented in a small portion of SCs, suggesting the presence of alternative genetic fusion. In this study, we examined the genetic fusion of 9 SCs using fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and next-generation sequencing (ArcherDx). Classic ETV6 exon 5-NTRK3 exon 15 fusion was detected in 8 of 9 SCs. The remaining tumor was negative for the ETV6-NTRK3 fusion but harbored a novel fusion, CTNNA1 exon 11-ALK in exon 20. Immunohistochemically, pan-TRK was positive in 8 tumors with ETV6-NTRK3 fusion but negative in an ALK-rearranged SC, while ALK was positive only in the ALK-rearranged tumor. Histologically, the ALK-rearranged tumor showed dominant macrocystic architecture. In conclusion, we found a case of SC with CTNNA1-ALK fusion. Because ALK fusion after exon 20 on the ALK side (upstream of the tyrosine kinase domain) has been reported to activate a carcinogenic kinase in various ALK-rearranged tumors, ALK inhibitors may be a possible therapeutic option for ALK-rearranged SC. In addition, ALK immunohistochemistry can be a screening tool for ALK-rearranged SC. This study also expands the molecular spectrum of this tumor beyond the ETV6 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase / genetics*
  • Anaplastic Lymphoma Kinase / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma / diagnosis
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • ETS Translocation Variant 6 Protein
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Proto-Oncogene Proteins c-ets / genetics*
  • Proto-Oncogene Proteins c-ets / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salivary Gland Neoplasms / diagnosis
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / metabolism
  • Salivary Gland Neoplasms / pathology
  • alpha Catenin / genetics*
  • alpha Catenin / metabolism

Substances

  • Anaplastic Lymphoma Kinase
  • Biomarkers, Tumor
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • alpha Catenin
  • ETS Translocation Variant 6 Protein
  • CTNNA1 protein, human
  • ALK protein, human