Schirwani Schaida, Theaker Jeff, Side Lucy, Moutasim Karwan
Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
Dermatology Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Am J Dermatopathol. 2025 Jun 20;47(8):586-588. doi: 10.1097/DAD.0000000000002982.
Spitz tumors are clinically and histologically challenging because of their close histologic resemblance to melanomas. Differentiating metastatic atypical Spitz tumors from melanoma has been a controversial issue for many decades. Diagnosis relies on expert pathologist review and a host of immunohistochemical and genomic testing including gene fusions in ALK, ROS, and NTRK, which has been informative in diagnosing and classifying these challenging lesions. Evidence suggest that atypical Spitz tumors associated with regional lymph node metastasis have good prognosis and do not spread to internal organs, however, cases of childhood melanomas (often with TERT mutations) can occur, often with a fatal outcome. Therefore, making a conclusive diagnosis is crucial when treating patients. In this study, we report a girl diagnosed with atypical Spitz tumor with lymph node metastasis at the age of 10 years. She has shown no recurrence after 20 years of follow-up. The formalin-fixed, paraffin-embedded tissue was retrospectively analyzed by next-generation sequencing and additional immunohistochemistry. PRAME immunohistochemistry was negative, as were ALK and ROS. No BRAF or TERT mutations were identified. No pathogenic or likely pathogenic variant was identified on testing lymphocyte DNA for familial malignant melanoma, including CDKN2A, CDK4, and BAP1 and a panel of 79 genes associated with childhood solid tumors.
斯皮茨瘤在临床和组织学上具有挑战性，因为它们在组织学上与黑色素瘤非常相似。几十年来，区分转移性非典型斯皮茨瘤和黑色素瘤一直是一个有争议的问题。诊断依赖于专家病理学家的审查以及一系列免疫组织化学和基因组检测，包括ALK、ROS和NTRK中的基因融合，这些检测在诊断和分类这些具有挑战性的病变方面具有参考价值。有证据表明，伴有区域淋巴结转移的非典型斯皮茨瘤预后良好，不会扩散到内脏器官，然而，儿童黑色素瘤（通常伴有TERT突变）病例可能会出现，且往往会导致致命后果。因此，在治疗患者时做出明确诊断至关重要。在本研究中，我们报告了一名10岁时被诊断为伴有淋巴结转移的非典型斯皮茨瘤的女孩。经过20年的随访，她没有复发。对福尔马林固定、石蜡包埋的组织进行了回顾性下一代测序和额外的免疫组织化学分析。PRAME免疫组织化学检测为阴性，ALK和ROS检测结果也为阴性。未发现BRAF或TERT突变。在检测淋巴细胞DNA中的家族性恶性黑色素瘤相关基因（包括CDKN2A、CDK4和BAP1）以及一组与儿童实体瘤相关的79个基因时，未发现致病或可能致病的变异。
