Original ArticlesMYB RNA In Situ Hybridization Facilitates Sensitive and Specific Diagnosis of Adenoid Cystic Carcinoma Regardless of Translocation StatusRooper, Lisa M. MD*,†; Lombardo, Kara A. BSc*,‡; Oliai, Bahram R. MD§; Ha, Patrick K. MD∥; Bishop, Justin A. MD¶Author Information Departments of *Pathology †Oncology ‡Urology, The Johns Hopkins University School of Medicine, Baltimore, MD §ProPath ¶Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX ∥Department of Otolaryngology, University of California at San Francisco, San Francisco, CA A portion of this data was presented in abstract form at the 2020 USCAP Annual Meeting in Los Angeles, CA. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Lisa M. Rooper, MD, The Johns Hopkins Medical Institutions, 401 North Broadway, Weinberg 2242, Baltimore, MD 21231-2410 (e-mail: [email protected]). The American Journal of Surgical Pathology: April 2021 - Volume 45 - Issue 4 - p 488-497 doi: 10.1097/PAS.0000000000001616 Buy Metrics Abstract Adenoid cystic carcinoma (AdCC) can demonstrate histologic and immunohistochemical (IHC) overlap with a wide range of salivary and nonsalivary tumors, especially in small biopsy specimens. While MYB fluorescence in situ hybridization (FISH) frequently is used to confirm the diagnosis of AdCC, the pathognomonic MYB-NFIB fusion is only present in 40% to 70% of cases. Likewise, although MYB RNA overexpression is seen in the vast majority of AdCC regardless of translocation status, MYB IHC has shown suboptimal specificity for this diagnosis. In this study, we sought to determine whether a novel chromogenic RNA in situ hybridization (ISH) platform could directly detect MYB RNA overexpression and offer a rapid diagnostic adjunct for AdCC. We performed MYB RNA ISH on 84 cases of AdCC as well as 128 other salivary tumors and 108 basaloid and sinonasal carcinomas that mimic AdCC. MYB RNA ISH was 92% sensitive for AdCC, including 97% of cases with MYB rearrangement and 83% without MYB rearrangement by FISH. It was also 89% specific for AdCC overall, with 95% specificity among other salivary tumors and 81% specificity in basaloid and sinonasal carcinomas. In contrast, MYB IHC was 94% sensitive but just 54% specific for AdCC. Overall, MYB RNA ISH provides superior sensitivity for the diagnosis of AdCC compared with MYB FISH and superior specificity compared with MYB IHC. This assay could provide a useful tool for rapidly confirming the diagnosis of AdCC in formalin-fixed, paraffin-embedded specimens. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.