Original ArticlesSalivary Secretory Carcinoma Harboring a Novel ALK Fusion Expanding the Molecular Characterization of Carcinomas Beyond the ETV6 GeneSasaki, Eiichi MD, PhD*; Masago, Katsuhiro MD, PhD*; Fujita, Shiro MD, PhD*; Suzuki, Hidenori MD, PhD†; Hanai, Nobuhiro MD, PhD†; Hosoda, Waki MD, PhD*Author Information Departments of *Pathology and Molecular Diagnostics †Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi Prefecture, Japan Conflicts of Interest and Source of Funding: Supported by the Aichi Cancer Research Foundation. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Eiichi Sasaki, MD, PhD, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Aichi Prefecture, Japan (e-mail: [email protected]). The American Journal of Surgical Pathology: July 2020 - Volume 44 - Issue 7 - p 962-969 doi: 10.1097/PAS.0000000000001471 Buy Metrics 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.