Owosho Adepitan A, Estilo Cherry L, Huryn Joseph M, Chi Ping, Antonescu Cristina R
College of Dental Medicine, University of New England, Portland, ME, 04103, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
Head Neck Pathol. 2018 Jun;12(2):151-159. doi: 10.1007/s12105-017-0841-y. Epub 2017 Jul 31.
Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST. MPNSTs with PRC2 loss are associated with complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3), which emerged as a reliable immunohistochemical marker in the diagnosis of sporadic and radiation induced MPNST. As the diagnosis of MPNST in the HN is particularly challenging to distinguish from melanoma and other sarcoma types, we carried out a clinicopathologic analysis on HN-MPNST patients managed at our institution over a 20-year period (1997-2016), using the latest diagnostic criteria including H3K27me3 staining and other molecular investigations. The overall survival of HN-MPNST was compared with other HN soft tissue sarcomas. The diagnosis of HN-MPNST was confirmed in 13 patients (seven males and six females), with a mean age of 31 years; with 3 (23%) patients being of pediatric age. The most common site was the neck soft tissue (77%). Two-thirds of patients (n = 9) had stigmata of NF1, three had prior radiotherapy and only one developed a de novo MPNST. All except one tumor (86%) tested showed loss of H3K27me3 expression, including all non-NF1 patients. The 2 and 5-year DSS rates were 50 and 30%. The 2-year DFS rate was 21%. Adverse predictors on DSS included adult age (p = 0.011), prior-history of RT (p = 0.003) and recurrence (p = 0.003). Compared to other molecularly confirmed subsets of HN sarcomas (Ewing and Ewing-like sarcoma, rhabdomyosarcoma and synovial sarcoma), HN-MPNST had the worst overall survival (p < 0.0001). We conclude that HN-MPNSTs are highly aggressive sarcomas associated with an unfavorable outcome and the utility of H3K27me3 IHC stains in the evaluation of MPNST is a reliable ancillary diagnostic adjunct.
头颈部高级别恶性外周神经鞘瘤（HN-MPNSTs）是罕见的、具有高度侵袭性的软组织肉瘤，其形态学和免疫表型特征与黑色素瘤及其他高级别肉瘤存在重叠，这给诊断带来了挑战，尤其是在散发性病例中。最近的研究发现，多梳抑制复合物2（PRC2）成分（包括EED或SUZ12基因）的功能缺失突变是高级别MPNST的主要发病机制之一。PRC2缺失的MPNST与组蛋白H3赖氨酸27位点（H3K27me3）的三甲基化完全缺失相关，H3K27me3已成为散发性和放射诱导性MPNST诊断中一种可靠的免疫组化标志物。由于HN部位MPNST的诊断与黑色素瘤及其他肉瘤类型的鉴别尤为困难，我们对在我院接受治疗的HN-MPNST患者进行了一项为期20年（1997 - 2016年）的临床病理分析，采用了包括H3K27me3染色及其他分子检测在内的最新诊断标准。将HN-MPNST的总生存率与其他HN软组织肉瘤进行了比较。确诊为HN-MPNST的患者有13例（7例男性，6例女性），平均年龄31岁；其中3例（23%）为儿童患者。最常见的部位是颈部软组织（77%）。三分之二的患者（n = 9）有神经纤维瘤病1型（NF1）的体征，3例曾接受过放疗，只有1例发生了新发MPNST。除1例肿瘤外，所有检测的肿瘤（86%）均显示H3K27me3表达缺失，包括所有非NF1患者。2年和5年疾病特异性生存率（DSS）分别为50%和30%。2年无病生存率（DFS）为21%。DSS的不良预测因素包括成年年龄（p = 0.011）、既往放疗史（p = 0.003）和复发（p = 0.003）。与其他经分子确诊的HN肉瘤亚组（尤因肉瘤和尤因样肉瘤、横纹肌肉瘤和滑膜肉瘤）相比，HN-MPNST的总生存率最差（p < 0.0001）。我们得出结论，HN-MPNST是高度侵袭性的肉瘤，预后不良，H3K27me3免疫组化染色在MPNST评估中的应用是一种可靠的辅助诊断手段。
