Histone H3.3 mutation in giant cell tumor of bone: an update in pathology

Hidetaka Yamamoto, Shin Ishihara, Yu Toda, Yoshinao Oda

Research output: Contribution to journalReview article

Abstract

Giant cell tumor of bone (GCTB) is a locally aggressive bone tumor that frequently shows local recurrence and occasionally shows malignant transformation to high-grade sarcoma. Histologically, conventional GCTB is composed mainly of three types of cells: mononuclear neoplastic cells with an osteoblastic precursor phenotype, mononuclear histiocytic cells, and osteoclast-like multinucleated giant cells. These cells interact with each other via the RANKL-RANK axis and other mechanisms for tumor formation. The vast majority of GCTBs were recently revealed to harbor H3F3A p.G34W mutation, and a minor subset have H3F3A p.G34L, p.G34M, p.G34R, or p.G34V mutation. H3.3 G34W mutant-specific immunohistochemistry is a highly sensitive and specific surrogate marker for H3F3A p.G34W mutation in GCTB and thus useful for differential diagnoses of histological mimics. H3.3 mutant-specific immunohistochemistry has also contributed to the understanding of the bone-forming ability of neoplastic cells of GCTB and the remarkable new bone formation after treatment with denosumab, an inhibitor of RANKL. In primary and secondary malignant GCTBs, the H3F3A gene allele can be preserved or lost with malignant transformation.

Original languageEnglish
JournalMedical Molecular Morphology
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Giant Cell Tumor of Bone
Histones
Pathology
Mutation
Immunohistochemistry
Bone and Bones
Osteoclasts
Giant Cells
Osteogenesis
Sarcoma
Neoplasms
Differential Diagnosis
Biomarkers
Alleles
Phenotype
Recurrence
Genes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology

Cite this

Histone H3.3 mutation in giant cell tumor of bone : an update in pathology. / Yamamoto, Hidetaka; Ishihara, Shin; Toda, Yu; Oda, Yoshinao.

In: Medical Molecular Morphology, 01.01.2019.

Research output: Contribution to journalReview article

@article{4f397366441240dfa092b9bb6e59f626,
title = "Histone H3.3 mutation in giant cell tumor of bone: an update in pathology",
abstract = "Giant cell tumor of bone (GCTB) is a locally aggressive bone tumor that frequently shows local recurrence and occasionally shows malignant transformation to high-grade sarcoma. Histologically, conventional GCTB is composed mainly of three types of cells: mononuclear neoplastic cells with an osteoblastic precursor phenotype, mononuclear histiocytic cells, and osteoclast-like multinucleated giant cells. These cells interact with each other via the RANKL-RANK axis and other mechanisms for tumor formation. The vast majority of GCTBs were recently revealed to harbor H3F3A p.G34W mutation, and a minor subset have H3F3A p.G34L, p.G34M, p.G34R, or p.G34V mutation. H3.3 G34W mutant-specific immunohistochemistry is a highly sensitive and specific surrogate marker for H3F3A p.G34W mutation in GCTB and thus useful for differential diagnoses of histological mimics. H3.3 mutant-specific immunohistochemistry has also contributed to the understanding of the bone-forming ability of neoplastic cells of GCTB and the remarkable new bone formation after treatment with denosumab, an inhibitor of RANKL. In primary and secondary malignant GCTBs, the H3F3A gene allele can be preserved or lost with malignant transformation.",
author = "Hidetaka Yamamoto and Shin Ishihara and Yu Toda and Yoshinao Oda",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00795-019-00238-1",
language = "English",
journal = "Medical Molecular Morphology",
issn = "1860-1480",

}

TY - JOUR

T1 - Histone H3.3 mutation in giant cell tumor of bone

T2 - an update in pathology

AU - Yamamoto, Hidetaka

AU - Ishihara, Shin

AU - Toda, Yu

AU - Oda, Yoshinao

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Giant cell tumor of bone (GCTB) is a locally aggressive bone tumor that frequently shows local recurrence and occasionally shows malignant transformation to high-grade sarcoma. Histologically, conventional GCTB is composed mainly of three types of cells: mononuclear neoplastic cells with an osteoblastic precursor phenotype, mononuclear histiocytic cells, and osteoclast-like multinucleated giant cells. These cells interact with each other via the RANKL-RANK axis and other mechanisms for tumor formation. The vast majority of GCTBs were recently revealed to harbor H3F3A p.G34W mutation, and a minor subset have H3F3A p.G34L, p.G34M, p.G34R, or p.G34V mutation. H3.3 G34W mutant-specific immunohistochemistry is a highly sensitive and specific surrogate marker for H3F3A p.G34W mutation in GCTB and thus useful for differential diagnoses of histological mimics. H3.3 mutant-specific immunohistochemistry has also contributed to the understanding of the bone-forming ability of neoplastic cells of GCTB and the remarkable new bone formation after treatment with denosumab, an inhibitor of RANKL. In primary and secondary malignant GCTBs, the H3F3A gene allele can be preserved or lost with malignant transformation.

AB - Giant cell tumor of bone (GCTB) is a locally aggressive bone tumor that frequently shows local recurrence and occasionally shows malignant transformation to high-grade sarcoma. Histologically, conventional GCTB is composed mainly of three types of cells: mononuclear neoplastic cells with an osteoblastic precursor phenotype, mononuclear histiocytic cells, and osteoclast-like multinucleated giant cells. These cells interact with each other via the RANKL-RANK axis and other mechanisms for tumor formation. The vast majority of GCTBs were recently revealed to harbor H3F3A p.G34W mutation, and a minor subset have H3F3A p.G34L, p.G34M, p.G34R, or p.G34V mutation. H3.3 G34W mutant-specific immunohistochemistry is a highly sensitive and specific surrogate marker for H3F3A p.G34W mutation in GCTB and thus useful for differential diagnoses of histological mimics. H3.3 mutant-specific immunohistochemistry has also contributed to the understanding of the bone-forming ability of neoplastic cells of GCTB and the remarkable new bone formation after treatment with denosumab, an inhibitor of RANKL. In primary and secondary malignant GCTBs, the H3F3A gene allele can be preserved or lost with malignant transformation.

UR - http://www.scopus.com/inward/record.url?scp=85075244914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075244914&partnerID=8YFLogxK

U2 - 10.1007/s00795-019-00238-1

DO - 10.1007/s00795-019-00238-1

M3 - Review article

AN - SCOPUS:85075244914

JO - Medical Molecular Morphology

JF - Medical Molecular Morphology

SN - 1860-1480

ER -