USP6 gene rearrangement in nodular fasciitis and histological mimics

Nodular fasciitis is known to be a benign mimic of sarcoma, both clinically and histologically. Accurate diagnosis, particularly on small biopsies, remains a challenge, as the morphology can be varied and the immunophenotype is essentially non-specific. Recently, rearrangement of the ubiquitin-specific protease 6 (USP6) gene has been reported as a recurrent and specific finding in nodular fasciitis. The aim of this this study was to evaluate the diagnostic utility of USP6 fluorescence in-situ hybridization (FISH) analysis in a subset of spindle-cell proliferations in which nodular fasciitis enters into the differential diagnosis.

A database search was performed at the Middlemore Hospital Histopathology Department. All in-house cases diagnosed between 2002 and March 2014 in which nodular fasciitis was considered as a differential diagnosis were retrospectively identified. Twenty cases were retrieved, reviewed and categorized as 'definite', 'possible' or 'definitely not' nodular fasciitis by consensus morphological opinion of three experienced pathologists. FISH analysis for USP6 rearrangement was performed in each case, with a commercially available break-apart probe. Of seven cases that were morphologically categorized as 'definite' nodular fasciitis, six were FISH-positive and one was FISH-negative. Of four cases categorized as 'possible' nodular fasciitis, one was FISH-positive and three were FISH-negative. Nine cases categorized as 'definitely not' nodular fasciitis were all FISH-negative. In the morphologically definitive cases, FISH analysis for USP6 had a sensitivity of 86% and specificity of 100% for a diagnosis of nodular fasciitis. The positive predictive value was 100%, and the negative predictive value 90%.

USP6 FISH is a useful ancillary test in cases where nodular fasciitis is a potential diagnostic consideration.