Department of Pathology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan.
Department of Pathology, Itabashi Central Clinical Laboratory, Tokyo, Japan.
Virchows Arch. 2021 Sep;479(3):559-564. doi: 10.1007/s00428-020-02992-5. Epub 2021 Mar 17.
Spitz tumors are genetically associated with activating HRAS point mutations or fusions of either ALK, ROS1, NTRK1, NTRK3, RET, MET, MERTK, LCK, BRAF, MAP3K8, or MAP3K3. All these driver gene alterations are mutually exclusive. We report two cases of agminated Spitz naevi with a GOPC-ROS1 fusion. Both cases occurred on the lower limb of young adults. Since adolescence, pigmented or pink-colored papules have been periodically arising in a limited area of skin. In one case, an ill-defined hyperpigmented macule known since childhood was present in the background. Morphologically, at least five lesions were analyzed from each patient. In one case, all were predominantly junctional pigmented Spitz naevi, and in the other case, all were compound unpigmented Spitz naevi. No atypical features were present. RNA-sequencing revealed a GOPC-ROS1 gene translocation in both cases. Split signals of ROS1 gene in fluorescence in situ hybridization were observed not only in the nests of spitzoid melanocytes but also in the bland basal melanocytes surrounding the proliferations. These findings suggest the presence of a GOPC-ROS1 mosaicism in melanocytes with further emergence of agminated Spitz naevi potentially triggered by other genetic alterations. This expands the spectrum of genetic anomalies described in agminated Spitz naevi and our understanding of the mechanisms involved in their emergence.
Spitz 肿瘤与激活 HRAS 点突变或 ALK、ROS1、NTRK1、NTRK3、RET、MET、MERTK、LCK、BRAF、MAP3K8 或 MAP3K3 的融合有关。所有这些驱动基因改变都是相互排斥的。我们报告了两例聚集性 Spitz 痣伴 GOPC-ROS1 融合。两例均发生于年轻成人下肢。自青春期以来，在皮肤的有限区域周期性出现色素沉着或粉红色丘疹。在一例中，存在一个自童年起就存在的边界不清的色素沉着斑。形态学上，每位患者至少分析了五个病变。在一个病例中，所有病变均主要为交界性色素性 Spitz 痣，另一个病例中，所有病变均为复合性无色素性 Spitz 痣。未见非典型特征。RNA 测序显示两例均存在 GOPC-ROS1 基因易位。荧光原位杂交中 ROS1 基因的分裂信号不仅在 Spitz 样黑素细胞巢中观察到，而且在周围增殖的无色素基底黑素细胞中也观察到。这些发现提示黑素细胞中存在 GOPC-ROS1 镶嵌现象，进一步出现聚集性 Spitz 痣可能是由其他遗传改变引发的。这扩展了聚集性 Spitz 痣中描述的遗传异常谱，并加深了我们对其发生机制的理解。
