USP6 RNA Chromogenic In Situ Hybridization Is Useful in the Diagnosis of Nodular Fasciitis and Aneurysmal Bone Cyst.

Abstract

Nodular fasciitis (NF) and aneurysmal bone cyst (ABC) are uncommon entities that can mimic malignant neoplasms and be challenging to diagnose. Molecularly, the majority of NF and ABC cases are characterized by USP6 rearrangements, which result in a promoter swap and aberrant upregulation of USP6 RNA. While fluorescence in situ hybridization (FISH) can be used to confirm USP6 rearrangement, it often requires multiple days to complete. Here, we examine if USP6 RNA chromogenic in situ hybridization (CISH) could aid in the diagnosis of NF and ABC. We found that USP6 RNA CISH was positive in 89% (16/18) of NF cases and 58% (7/12) of ABC cases. Importantly, in histologic mimics of NF and ABC, USP6 RNA CISH was negative. USP6 FISH or next-generation sequencing was performed on all NF and ABC cases, one consult case diagnosed as benign fibroblastic neoplasm with associated ossification, and a subset of histologic mimics to assess for USP6 rearrangements. Ninety-two percent (22/24) of cases with USP6 rearrangement also demonstrated positive USP6 RNA CISH staining, while 100% (19/19) of cases that were negative for USP6 rearrangement, including 2 NF, 4 ABC, and 13 histologic mimics, were also negative for USP6 RNA CISH. One case was inconclusive by FISH, but positive by CISH. Our results indicate that USP6 RNA CISH can serve as a useful tool in the diagnosis of NF and ABC.