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

Abstract

OBJECTIVES:

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.

• Authors: Jeffrey K Mito, Xiaohua Qian, Leona A Doyle, Jason L Hornick, Vickie Y Jo
• Journal: American journal of clinical pathology (Am J Clin Pathol) Vol. 148 Issue 2 Pg. 179-189 (Aug 01 2017) ISSN: 1943-7722 [Electronic] England
• PMID: 28898989 (Publication Type: Journal Article)
• Copyright: © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: [email protected]

Chemical References

• Biomarkers, Tumor
• Histones

Topics

• Adult
• Biomarkers, Tumor (analysis)
• Biopsy
• Biopsy, Fine-Needle
• DNA Methylation
• Female
• Histones (analysis, biosynthesis)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Neurilemmoma (diagnosis)