Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Mod Pathol. 2017 Dec;30(12):1710-1719. doi: 10.1038/modpathol.2017.97. Epub 2017 Aug 4.
The diagnosis of malignant peripheral nerve sheath tumors can be challenging and other spindle cell sarcomas commonly enter in the differential diagnosis. Loss of trimethylation at lysine 27 of histone-H3 (H3K27me3) by immunohistochemistry was recently described in malignant peripheral nerve sheath tumors. However, its specificity remains controversial. We therefore studied 82 synovial sarcomas, 39 malignant peripheral nerve sheath tumors, and 10 fibrosarcomatous dermatofibrosarcoma protuberans for H3K27me3 loss by immunohistochemistry. The diagnoses were based on morphology, immunophenotype, and genetics based on WHO classification. H3K27me3 immunohistochemistry was scored by two pathologists based on fraction of cells with nuclear staining (score 0 to 3+). Loss of H3K27me3 (score 0) was seen in 44% of malignant peripheral nerve sheath tumors and 9% of synovial sarcomas yielding positive and negative predictive values of 71% and 77%, respectively. Loss of H3K27me3 was seen in 10% of fibrosarcomatous dermatofibrosarcoma protuberans, yielding positive and negative predictive values of 94 and 29% in the differential diagnosis of malignant peripheral nerve sheath tumor versus fibrosarcomatous dermatofibrosarcoma protuberans. Partial loss (score 1-2) was common in all three tumor types. Among malignant peripheral nerve sheath tumors, there was no significant association between H3K27me3 loss and gender, tumor site, or size, and progression-free or overall survival. Patients with tumors with H3K27me3 loss were younger than those with tumors with retained H3K27me3 expression (P=0.011). H3K27me3 expression was lost in 50 and 31% of sporadic and Neurofibromatosis-associated malignant peripheral nerve sheath tumors, respectively (P=0.25).Complete H3K27me3 loss is a moderately sensitive and relatively specific marker for the diagnosis of malignant peripheral nerve sheath tumor when the differential diagnosis includes synovial sarcoma and fibrosarcomatous dermatofibrosarcoma protuberans. Partial loss has limited diagnostic utility. H3K27me3 status does not show significant association with clinical outcome in malignant peripheral nerve sheath tumors.
恶性外周神经鞘瘤的诊断具有挑战性，其他梭形细胞肉瘤通常也需要进行鉴别诊断。最近在恶性外周神经鞘瘤中描述了组蛋白 H3 赖氨酸 27 三甲基化（H3K27me3）的免疫组织化学缺失。然而，其特异性仍存在争议。因此，我们研究了 82 例滑膜肉瘤、39 例恶性外周神经鞘瘤和 10 例纤维肉瘤样隆突性皮肤纤维肉瘤，通过免疫组织化学方法检测 H3K27me3 的缺失。诊断基于形态学、免疫表型和基于世界卫生组织分类的遗传学。两位病理学家根据核染色细胞的分数（评分 0 至 3+）对 H3K27me3 免疫组织化学评分。44%的恶性外周神经鞘瘤和 9%的滑膜肉瘤出现 H3K27me3 缺失（评分 0），阳性预测值和阴性预测值分别为 71%和 77%。10%的纤维肉瘤样隆突性皮肤纤维肉瘤出现 H3K27me3 缺失，在恶性外周神经鞘瘤与纤维肉瘤样隆突性皮肤纤维肉瘤的鉴别诊断中，阳性预测值和阴性预测值分别为 94%和 29%。所有三种肿瘤类型中都常见部分缺失（评分 1-2）。在恶性外周神经鞘瘤中，H3K27me3 缺失与性别、肿瘤部位或大小、无进展生存或总生存之间无显著相关性。H3K27me3 缺失的肿瘤患者比保留 H3K27me3 表达的肿瘤患者年轻（P=0.011）。散发性和神经纤维瘤病相关的恶性外周神经鞘瘤中分别有 50%和 31%出现 H3K27me3 缺失（P=0.25）。当鉴别诊断包括滑膜肉瘤和纤维肉瘤样隆突性皮肤纤维肉瘤时，完全 H3K27me3 缺失是诊断恶性外周神经鞘瘤的一种中等敏感性和相对特异性标志物。部分缺失的诊断效用有限。在恶性外周神经鞘瘤中，H3K27me3 状态与临床结局无显著相关性。
