Morphologic features in a series of 352 Spitz melanocytic proliferations help predict their oncogenic drivers
Morphologic features in a series of 352 Spitz melanocytic proliferations help predict their oncogenic drivers
复制标题
一系列 352 个 Spitz 黑素细胞增殖的形态学特征有助于预测其致癌驱动因素
DOI：
10.1007/s00428-021-03227-x
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发表时间：
2021
期刊：
影响因子：
3.5
通讯作者：
A. de la Fouchardière
中科院分区：
文献类型：
--
作者：
T. Kervarrec;D. Pissaloux;F. Tirode;M. Samimi;J. Jacquemus;Christine Castillo;A. de la Fouchardière
斯皮茨痣是惰性黑素细胞肿瘤，优先在儿童期和儿童期后出现。在过去的几十年里，在黑色素瘤中很少检测到的复发性致癌驱动因素在斯皮茨黑素细胞增殖中被发现。因此，对此类驱动程序的检测似乎是区分这两个实体的相关诊断工具。有趣的是，形态特征可能与致癌驱动因素相关。因此，本研究的目的是评估先前确定的形态标准的性能，以预测特定驱动因素的存在。本研究总共纳入了 352 个 Spitz 黑素细胞增殖，这些细胞要么具有基因鉴定的致癌驱动因素，要么通过免疫组织化学研究了 ALK、ROS1 和 NTRK1 过度表达。根据分子状态对病例的微观特征进行盲目评估，并应用似然比检验（LHR）评估先前描述的预测分子状态的形态学标准的性能。总体而言，76% 的病例中发现了致癌驱动因素 (n= 268/352)。没有微观特征可以可靠地预测 ROS1 和 NTRK1 过表达病例。相比之下，丛状模式有助于识别 ALK 过度表达病例 (LHR(+) = 6.14）。重要的是，假神经鞘瘤变异高度提示 NTRK3 重排病例 (LHR(+) = 43）。此外，非典型/恶性肿瘤 (LHR(+) = 5.18)、严重细胞异型性 (LHR(+) = 5.07) 和 p16 缺失 (LHR(+) = 14) 有助于识别 MAP3K8 重排病例，而存在片状结构 (LHR(+) = 5.39) 和显着的基质纤维化(LHR(+)=5.06)是BRAF融合肿瘤的预测因素。总之，我们的研究证实 ALK 过表达、NTRK3、MAP3K8 和 BRAF 重排病例具有独特的形态特征，允许在显微镜下识别。
Spitz nevi are indolent melanocytic tumors arising preferentially during and after childhood. Over the last decades, recurrent oncogenic drivers, sparsely detected in melanoma, were identified in Spitz melanocytic proliferations. Therefore, the detection of such drivers appears as a relevant diagnostic tool to distinguish both entities. Interestingly, morphologic features might correlate with the oncogenic drivers. Thus, the goal of this study was to assess the performances of previously identified morphological criteria to predict the presence of specific drivers. In total, 352 Spitz melanocytic proliferations either with a genetically identified oncogenic driver or investigated for ALK, ROS1, and NTRK1 overexpression by immunohistochemistry were enrolled in the present study. The microscopic features of the cases were assessed blindly with regards to the molecular status and, performances of previously described morphological criteria to predict the molecular status were assessed applying the likelihood-ratio test (LHR). Overall, an oncogenic driver was identified in 76% of the cases (n= 268/352). No microscopic features allowed the reliable prediction of ROS1- and NTRK1-overexpressing cases. By contrast, a plexiform pattern can contribute to the recognition of ALK-overexpressing cases (LHR(+) = 6.14). Importantly, the pseudo-schwannoma variant was highly suggestive ofNTRK3-rearranged cases (LHR(+) = 43). Moreover, atypical/malignant tumor (LHR(+) = 5.18), severe cellular atypia (LHR(+) = 5.07), and p16 loss (LHR(+) = 14) contribute to the recognition ofMAP3K8-rearranged cases, while the presence of a sheet-like architecture (LHR(+) = 5.39) and a marked fibrosis of the stroma (LHR(+)=5.06) were predictive ofBRAF-fused tumors. To conclude, our study confirms ALK-overexpressing,NTRK3-, MAP3K8-, andBRAF-rearranged cases harbored distinct morphologic features allowing their microscopic recognition.