Validation of Fluorescence in situ Hybridization Testing of USP6 Gene Rearrangement for Diagnosis of Primary Aneurysmal Bone Cyst.

Ubiquitin specific protease 6 (USP6) gene rearrangement has been reported in approximately 70%-75% of aneurysmal bone cyst cases. We hypothesize that fluorescence in situ hybridization (FISH) testing of this marker will be useful in the pathological differentiation of primary aneurysmal bone cyst (ABC), secondary ABC, giant cell tumor of bone (GCT), and telangiectatic osteosarcoma (TOS) which are morphologically similar. This study aims to evaluate the efficacy of this test and validate it for diagnostic use.

FISH was performed in primary ABC, secondary ABC, GCT and TOS using dual color USP6 gene break apart probes. The sensitivity, specificity, positive predictive value, and negative predictive values were calculated.

Primary ABC demonstrates USP6 rearrangement. All secondary ABC, GCT and TOS were negative. The test sensitivity and specificity in primary ABC were 53% (9/17) and 100% (18/18), respectively. The positive predictive value and negative predictive value were 100% (9/9) and 69% (18/26), respectively.

The USP6 gene break apart detected by FISH is validated as a novel diagnostic tool for primary ABC in our laboratory. This test could be used to study the predictive value of USP6 targeted therapy for primary ABC in the near future.