Department of Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
Department of Pathology, Umeå University, Umeå, Sweden.
Ann Diagn Pathol. 2023 Dec;67:152215. doi: 10.1016/j.anndiagpath.2023.152215. Epub 2023 Oct 5.
Spitz tumors are melanocytic neoplasms morphologically characterized by spindled and/or epithelioid cells and specific stromal and epidermal changes associated with mutually exclusive fusion kinases involving ALK, ROS1, NTRK1, NTRK2, NTRK3, MET and RET, BRAF and MAP3K8 genes or, less commonly, HRAS mutation. RAF1 fusions have been recently detected in cutaneous melanocytic neoplasms, including conventional melanoma, congenital nevus and BAP-1 inactivated tumors. We report herewith three Spitz neoplasms with a RAF1 fusion, including a previously reported CTDSPL::RAF1 fusion and two novel PPAP2B::RAF1 and ATP2B4::RAF1 fusions. Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.
Spitz 肿瘤是一种黑素细胞肿瘤，其形态学特征为梭形和/或上皮样细胞，以及与相互排斥的融合激酶相关的特定基质和表皮改变，这些激酶涉及 ALK、ROS1、NTRK1、NTRK2、NTRK3、MET 和 RET、BRAF 和 MAP3K8 基因，或较少见的 HRAS 突变。RAF1 融合最近在皮肤黑素细胞肿瘤中被检测到，包括常规黑色素瘤、先天性痣和 BAP-1 失活肿瘤。我们在此报告三例具有 RAF1 融合的 Spitz 肿瘤，包括之前报道的 CTDSPL::RAF1 融合和两个新的 PPAP2B::RAF1 和 ATP2B4::RAF1 融合。两个病例被归类为 Spitz 痣，而其余肿瘤在诊断时被归类为 Spitz 黑色素瘤，因为存在 9p21 纯合缺失和阳性前哨淋巴结活检。我们建议，具有 RAF1 融合的黑素细胞肿瘤可能代表 Spitz 肿瘤的一个新亚组，具有 RAF1 融合代表致癌驱动因素。
