Diagnostic value of histone 3 mutations in osteoclast-rich bone tumors.

Nohr E, Lee LH, Cates JM, Perizzolo M, Itani D
Hum Pathol. 2017 68: 119-127

PMID: 28882701 · DOI:10.1016/j.humpath.2017.08.030

Differentiating osteoclast-rich lesions of bone (giant cell tumor of bone [GCTB], chondroblastoma [CBA], and aneurysmal bone cyst [ABC]) can be challenging, especially in small biopsies or fine-needle aspirations. Mutations affecting codons 34 and 36 of either H3 Histone Family Member 3A (H3F3A) and/or 3B (H3F3B) are characteristically seen in GCTB and CBAs. We devised a simple assay to identify these mutations and evaluated its applicability for routine clinical diagnosis. One hundred twenty-four tissue specimens from 108 patients (43 GCTBs, 38 CBAs and 27 ABCs) were collected from the archives of the Calgary Laboratory Services/University of Calgary and Vanderbilt University Medical Center. Histology was reviewed by an expert orthopedic pathologist. A single base extension assay (SNaPshot) is used to interrogate each nucleotide in codons 34 and 36 of H3F3A and codon 36 of H3F3B. Final diagnoses were generated after re-reviewing cases and incorporating molecular findings. Of 43 GCTBs, 38 (88%) had an H3F3A G34W mutation; 35 of 38 CBAs (92%) had a K36M mutation in either H3F3B (N = 31; 82%) or H3F3A (N = 4; 11%); none of 27 ABCs had a tested mutation. Molecular findings changed the histomorphologic diagnosis in 5 cases (3 GCTB changed to ABC, and 2 ABC changed to GCTB). These findings support the diagnostic utility of mutational analysis for this differential diagnosis in certain challenging cases when clinicoradiologic and histomorphologic features are not definitive, particularly for distinguishing cellular ABC versus GCTB with secondary ABC.

Copyright © 2017 Elsevier Inc. All rights reserved.

MeSH Terms (27)

Adolescent Adult Aged Alberta Biomarkers, Tumor Bone Cysts, Aneurysmal Bone Neoplasms Child Chondroblastoma Diagnosis, Differential Disease-Free Survival DNA Mutational Analysis Female Genetic Predisposition to Disease Giant Cell Tumor of Bone Histones Humans Kaplan-Meier Estimate Male Middle Aged Mutation Osteoclasts Phenotype Predictive Value of Tests Tennessee Time Factors Young Adult

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