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

Hidetaka Yamamoto, Shin Ishihara, Yu Toda, Yoshinao Oda

研究成果: ジャーナルへの寄稿評論記事

1 引用 (Scopus)


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.

ジャーナルMedical Molecular Morphology
出版物ステータス出版済み - 3 1 2020


All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology