Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy

Cancer Cytopathology
Inga-Marie SchaeferXiaohua Qian

Abstract

Diagnosing giant cell-rich bone tumors can be challenging on limited biopsies. H3 histone family member 3A (H3F3A) (G34W/V/R/L) mutations are present in the majority of giant cell tumors (GCTs) of bone and H3 histone family member 3B (H3F3B) (K36M) mutations are present in nearly all chondroblastomas, but are absent in histologic mimics. Mutation-specific immunohistochemistry (IHC) is highly specific for GCT and chondroblastoma in surgical excisions. The objective of the current study was to validate H3G34W and H3K36M IHC in the diagnosis of giant cell-rich bone tumors on fine-needle aspiration and core needle biopsy specimens. IHC was performed using monoclonal antibodies against histone H3.3 G34W and K36M in GCTs of bone (26 cases, including 2 malignant cases), GCT of Paget disease (1 case), chondroblastoma (8 cases), aneurysmal bone cyst (7 cases), and osteosarcoma (13 cases) with available fine-needle aspiration and/or core needle biopsy specimens from 2 institutions. H3F3A and H3F3B Sanger sequencing was performed on all 4 H3G34W IHC-negative GCTs. IHC for H3G34W was positive in 22 of 26 GCTs (85%) and negative in all histologic mimics. IHC for H3K36M was positive in all 8 chondroblastomas and negative in all histologic mi...Continue Reading

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Citations

Nov 2, 2018·Genes, Chromosomes & Cancer·William J Anderson, Jason L Hornick
May 16, 2020·The American Journal of Surgical Pathology·Iva BrčićAndrew E Rosenberg
Jul 1, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·David J PapkeJason L Hornick
Aug 11, 2020·The American Journal of Surgical Pathology·Darcy A KerrAndrew E Rosenberg
Nov 15, 2020·Pathology·Kenon ChuaVictor Kwan Min Lee
Aug 23, 2018·Advances in Anatomic Pathology·Inga-Marie Schaefer, Jason L Hornick
Feb 12, 2021·Nature Reviews. Cancer·Flávia G GhiraldiniEmily Bernstein
Feb 24, 2021·Orthopaedic Surgery·Haoran MuZhengdong Cai
May 3, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Y ChenY Zhang

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