H3-3A gene mutation analysis in giant cell tumor of bone and its histologic mimics: A single institutional study from India

IF 1.4 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology Pub Date : 2026-06-01 Epub Date: 2026-01-08 DOI:10.1016/j.anndiagpath.2026.152606

Shantveer G. Uppin , Monalisa Hui , Derin Mary Thomas , Megha S. Uppin , Vinay Nalla , K. Nageshwara Rao , Rajeev Reddy , Himakanth Lingala

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引用次数: 0

Abstract

Though the diagnostic utility of H3.3G34W immunohistochemistry (IHC) for giant cell tumor of bone (GCTB) is well established, it is limited by a proportion of cases with variant H3-3A mutations [H3-3A: c.104G>T p. Gly35Val (G34V), H3-3A: c.103G>A p. Gly35Arg (G34R), H3-3A: c.103_104delinsCT p. Gly35Leu (G34L)], wild-type genotype and H3-3A:c.103G>T p. Gly35Trp (G34W) mutation identified by sequencing but not by IHC. In this study, the H3-3A gene mutation by Sanger sequencing was analyzed in a large cohort of GCTB and its histological mimics. Sequencing of the H3-3A gene was performed to detect mutations in 148 GCTBs and 57 histologic mimics. The other osteoclast giant cell containing lesions histologically mimicking GCTB included were chondroblastoma (22), aneurysmal bone cyst (11), chondromyxoid fibroma (6), telangiectatic osteosarcoma (6), brown tumor of hyperparathyroidism (4), clear cell chondrosarcoma (3), osteoid osteoma (2), osteoblastoma (2) and giant cell reparative granuloma (1). Of the 148 GCTBs tested, 129 showed H3-3A gene mutations by Sanger sequencing and remaining 19 were wild type. The different H3-3A mutations detected included 126 H3-3A:c.103G>T p. Gly35Trp (G34W), one each of H3-3A: c.103G>A p. Gly35Arg (G34R), H3-3A: c.104G>T p. Gly35Val (G34V) and H3-3A: c.103_104delinsCT p. Gly35Leu (G34L). The results of H3-3A gene sequencing were in concordance with the immunohistochemical expression for H3.3G34W/R/V in 129 tumors. All the 57 osteoclast giant cell-containing lesions, other than GCTB, except one (1) case of chondroblastoma, did not show any mutations in the H3-3A gene. The latter case showed H3-3A: c.110A>T p. Lys37Met (K36M) mutation. The H3-3A gene sequencing assay demonstrated a sensitivity of 87.16% and an absolute specificity of 100% among the cases analyzed in the study. Determination of the H3-3A gene mutation by sequencing is a highly sensitive and absolutely specific diagnostic tool for the diagnosis of GCTB and differentiation from its histologic mimics.

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骨巨细胞瘤及其组织模拟物的H3-3A基因突变分析：来自印度的单一机构研究

虽然H3.3G34W免疫组织化学（IHC）对骨巨细胞瘤（GCTB）的诊断作用已经得到了很好的建立，但它受到一定比例的H3-3A变异突变病例的限制[H3-3A: c.104G>T p. Gly35Val (G34V), H3-3A:c.103G> a p. Gly35Arg (G34R), H3-3A: c.103_104delinsCT p. Gly35Leu (G34L)]，野生型基因型和H3-3A:c.103G>T p. Gly35Trp （G34W）突变通过测序而非IHC鉴定。在本研究中，通过Sanger测序分析了H3-3A基因突变在一个大队列的GCTB及其组织学模拟。对H3-3A基因进行测序，检测148个GCTBs和57个组织学模拟物的突变。其他组织学上类似GCTB的破骨细胞巨细胞病变包括成软骨细胞瘤（22例）、动脉瘤性骨囊肿（11例）、软骨粘液样纤维瘤（6例）、毛细血管扩张性骨肉瘤（6例）、甲状旁腺功能亢进棕色肿瘤（4例）、透明细胞软骨肉瘤（3例）、类骨骨瘤（2例）、成骨细胞瘤（2例）和巨细胞修复性肉芽肿（1例）。148个GCTBs中，Sanger测序显示H3-3A基因突变129个，其余19个为野生型。检测到的不同H3-3A突变包括126个H3-3A:c.103G>T . Gly35Trp (G34W), H3-3A:c.103G> A p. Gly35Arg (G34R), H3-3A: c.104G>T . Gly35Val （G34V）和H3-3A: c.103_104delinsCT p. Gly35Leu （G34L）。H3-3A基因测序结果与129例肿瘤中H3.3G34W/R/V的免疫组化表达一致。除1例成软骨细胞瘤外，其余57例含破骨细胞巨细胞病变均未见H3-3A基因突变。后者表现为H3-3A: c.110A>T . p. Lys37Met （K36M）突变。H3-3A基因测序法在本研究分析的病例中灵敏度为87.16%，绝对特异性为100%。通过测序检测H3-3A基因突变是一种高度敏感和绝对特异性的诊断工具，可用于GCTB的诊断和与组织学模拟物的区分。

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来源期刊

Annals of Diagnostic Pathology 医学-病理学

CiteScore

3.90

自引率

5.00%

发文量

149

审稿时长

26 days

期刊介绍： A peer-reviewed journal devoted to the publication of articles dealing with traditional morphologic studies using standard diagnostic techniques and stressing clinicopathological correlations and scientific observation of relevance to the daily practice of pathology. Special features include pathologic-radiologic correlations and pathologic-cytologic correlations.