Spitzoid neoplasms are a challenging group of cutaneous melanocytic proliferations. They are characterized by epithelioid and/or spindle‐shaped melanocytes and classified as benign Spitz nevi (SN), atypical Spitz tumors (AST), or malignant Spitz tumors (MST). The intermediate AST category represents a diagnostically challenging group since on purely histopathological grounds, their benign or malignant character remains unpredictable. This results in uncertainties in patient treatment and prognosis. The molecular properties of Spitzoid lesions, especially their transcriptomic landscape, remain poorly understood, and genomic alterations in melanoma‐associated oncogenes are typically absent. The aim of this study was to characterize their transcriptome with digital mRNA expression profiling. Formalin‐fixed paraffin‐embedded samples (including 27 SN, 10 AST, and 14 MST) were analyzed using the NanoString nCounter PanCancer Pathways Panel. The number of significantly differentially expressed genes in SN vs. MST, SN vs. AST, and AST vs. MST was 68, 167, and 18, respectively. Gene set enrichment analysis revealed upregulation of pathways related to epithelial–mesenchymal transition and immunomodulatory‐, angiogenesis‐, hormonal‐, and myogenesis‐associated processes in AST and MST. A molecular signature of SN vs. MST was discovered based on the top‐ranked most informative genes: NRAS, NF1, BMP2, EIF2B4, IFNA17, and FZD9. The AST samples showed intermediate levels of the identified signature. This implies that the gene signature can potentially be used to distinguish high‐grade from low‐grade AST with a larger study cohort in the future. This combined histopathological and transcriptomic methodology is promising for prospective diagnostics of Spitzoid neoplasms and patient management in dermatological oncology.

中文翻译：

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用于对具有挑战性的 Spitzoid 黑色素细胞肿瘤进行分类的数字 mRNA 表达特征。

Spitzoid 肿瘤是一组具有挑战性的皮肤黑色素细胞增生。它们的特征是上皮样和/或纺锤形黑色素细胞，分为良性 Spitz 痣 (SN)、非典型 Spitz 肿瘤 (AST) 或恶性 Spitz 肿瘤 (MST)。中间 AST 类别代表诊断上具有挑战性的组，因为纯粹基于组织病理学，它们的良性或恶性特征仍然不可预测。这导致患者治疗和预后的不确定性。Spitzoid 病变的分子特性，尤其是它们的转录组学景观，仍然知之甚少，并且通常不存在黑色素瘤相关癌基因的基因组改变。本研究的目的是通过数字 mRNA 表达谱来表征它们的转录组。福尔马林固定石蜡包埋样品（包括 27 SN、10 AST 和 14 MST) 使用 NanoString nCounter PanCancer Pathways Panel 进行分析。SN 与 MST、SN 与 AST、AST 与 MST 中显着差异表达的基因数分别为 68、167 和 18。基因集富集分析揭示了 AST 和 MST 中与上皮间充质转化和免疫调节、血管生成、激素和肌生成相关过程相关的通路上调。根据排名最高的信息量最大的基因，发现了 SN 与 MST 的分子特征：基因集富集分析揭示了 AST 和 MST 中与上皮间充质转化和免疫调节、血管生成、激素和肌生成相关过程相关的通路上调。根据排名最高的信息量最大的基因，发现了 SN 与 MST 的分子特征：基因集富集分析揭示了 AST 和 MST 中与上皮间充质转化和免疫调节、血管生成、激素和肌生成相关过程相关的通路上调。根据排名最高的信息量最大的基因，发现了 SN 与 MST 的分子特征：NRAS、NF1、BMP2、EIF2B4、IFNA17和FZD9。AST 样本显示出中等水平的识别特征。这意味着基因特征有可能在未来在更大的研究队列中用于区分高级别和低级别 AST。这种结合组织病理学和转录组学的方法有望用于 Spitzoid 肿瘤的前瞻性诊断和皮肤肿瘤学中的患者管理。