Unusual split green-orange signals in USP6 fluorescence in situ hybridization in a malignant peripheral nerve sheath tumor with a novel NF1-SCIMP fusion: a potential diagnostic pitfall

Abstract

Deletion of the neurofibromatosis 1 (NF1) gene is common, but NF1 rearrangement or fusion has rarely been reported in peripheral nerve sheath tumors. Here, we present a case of malignant peripheral nerve sheath tumor (MPNST) in a 36-year-old Chinese female. Histologically, the lesion was composed of spindle cells with moderate atypia, immature bone, and atypical cartilage elements. Fluorescence in situ hybridization (FISH) for USP6 revealed green-orange split signals, strongly suggesting the presence of USP6 rearrangement. Subsequent next-generation sequencing-based technology analyses revealed t(17,17) (p13.2, q11.2) intrachromosomal translocation resulting in a novel NF1-SCIMP fusion gene along with NF1 deletion. However, USP6 fusion was not identified. To the best of our knowledge, this is the first case with a confirmed NF1 gene fusion partner in a peripheral nerve sheath tumor. Notably, rearrangement of the SCIMP may cause a pitfall in the interpretation of USP6 FISH results.

Keywords: Malignant peripheral nerve sheath tumor; NF1-SCIMP fusion; USP6 rearrangement.