Role of Histone H3K27 Trimethylation Loss as a Marker for Malignant Peripheral Nerve Sheath Tumor in Fine-Needle Aspiration and Small Biopsy Specimens.

Objective: Accurate diagnosis of malignant peripheral nerve sheath tumor (MPNST) is often challenging on fine-needle aspiration (FNA) or core needle biopsy. Recurrent mutations in EED and SUZ12, which encode subunits of polycomb repressive complex 2 (PRC2), have been identified in 70% to 92% of MPNSTs; PRC2 inactivation leads to loss of trimethylation of lysine 27 of histone H3 (H3K27me3). We evaluated the utility of H3K27me3 immunohistochemistry for distinguishing MPNST from its cytomorphologic mimics.

Methods: H3K27me3 immunohistochemistry was performed on 180 cases of spindle cell neoplasms sampled by FNA (n = 66) and needle biopsy (n = 114), and loss of nuclear staining was scored. Tumor types included MPNST, dedifferentiated liposarcoma, schwannoma, solitary fibrous tumor, leiomyosarcoma, melanoma, synovial sarcoma, sarcomatoid carcinoma, gastrointestinal stromal tumor, desmoid fibromatosis, low-grade fibromyxoid sarcoma, and unclassified spindle cell sarcoma/undifferentiated pleomorphic sarcoma.

Results: Complete loss of H3K27me3 was observed in 54% (13/24) of MPNSTs. In contrast, only two (of 156) histologic mimics showed complete loss of H3K27me3. Partial loss of H3K27me3 was present in a subset of cases (26/180), including both MPNST and non-MPNSTs.

Conclusions: Complete loss of H3K27me3 is a highly specific (98.7%) marker of MPNST that can distinguish MPNST from cytomorphologic mimics in FNA cell block and small biopsy specimens.