MYB RNA In Situ Hybridization Facilitates Sensitive and Specific Diagnosis of Adenoid Cystic Carcinoma Regardless of Translocation Status.

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.