Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India.
Department of Orthopaedics, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India.
Indian J Pathol Microbiol. 2022 Jul-Sep;65(3):617-629. doi: 10.4103/ijpm.ijpm_265_21.
The diagnosis of giant cell tumor of bone (GCTB) is difficult in small biopsies with unusual age of presentation, location, and extensive secondary changes. Most of the GCTBs harbor H3F3A G34W mutations with a subset of cases showing alternate G34V, G34R, and G34L mutations.
To analyze the expression of anti-histone H3.3G34W antibody in different cellular components of GCTB across different locations and presentations (including the unusual ones) and validate the utility of this antibody in the diagnosis of GCTB and differentiate it from the other osteoclast-like giant-cell-rich lesions.
Immunohistochemistry was performed using anti-histone H3.3G34W antibody in the diagnosed cases of GCTB (136 cases of GCTB from 133 patients, including two malignant GCTBs) and other giant cell-containing lesions (62 cases). The presence of unequivocal crisp nuclear staining was considered positive.
Immunohistochemistry revealed unequivocal nuclear positivity in the mononuclear cells in 87.3% of the cases of GCTB. Of these, most showed diffuse expression with moderate to strong intensity staining. The positive staining was restricted to the nuclei of mononuclear cells with the nuclei of osteoclastic giant cells being distinctly negative. In addition to conventional GCTBs, two cases each of multicentric and malignant GCTB showed positive staining. The other giant-cell containing lesions were distinctly negative. The present study showed a sensitivity of 87.3% with specificity and positive predictive value of 100%.
The anti-histone G34W antibody is a highly sensitive and specific marker for the diagnosis of GCTB and differentiating it from its mimics. The positive staining is restricted to the mononuclear cell component of GCTB with sparing the osteoclastic giant cells further reiterating the fact that the mononuclear stromal cells are the true neoplastic component of GCTB.
在具有异常发病年龄、位置和广泛继发改变的小活检中，骨巨细胞瘤（GCTB）的诊断较为困难。大多数 GCTB 存在 H3F3A G34W 突变，少数病例显示出 G34V、G34R 和 G34L 突变的替代突变。
分析不同位置和表现（包括不常见表现）的 GCTB 中不同细胞成分的抗组蛋白 H3.3G34W 抗体的表达，并验证该抗体在 GCTB 诊断中的应用价值，并将其与其他破骨细胞样巨细胞丰富病变区分开来。
对 133 例患者的 136 例 GCTB（包括 2 例恶性 GCTB）和其他含巨细胞病变（62 例）进行抗组蛋白 H3.3G34W 抗体的免疫组织化学染色。核内出现明确的核染色被认为是阳性。
免疫组织化学染色显示 87.3%的 GCTB 病例单核细胞核内阳性。其中大多数表现为弥漫性表达，染色强度为中到强。阳性染色仅限于单核细胞的核内，破骨细胞样巨细胞的核内染色明显为阴性。除了传统的 GCTB 外，2 例多中心性 GCTB 和 2 例恶性 GCTB 也显示阳性染色。其他含巨细胞病变则明显为阴性。本研究的敏感性为 87.3%，特异性和阳性预测值均为 100%。
抗组蛋白 G34W 抗体是诊断 GCTB 并将其与模拟物区分开来的高度敏感和特异的标志物。阳性染色仅限于 GCTB 的单核细胞成分，而破骨细胞样巨细胞不受影响，进一步强调了单核基质细胞是 GCTB 的真正肿瘤成分的事实。
