Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Division of Molecular Pathology, Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
J Cutan Pathol. 2023 Oct;50(10):913-921. doi: 10.1111/cup.14482. Epub 2023 Jul 5.
The conventionally understood pathogenesis of agminated Spitz nevi includes a mosaic HRAS mutation followed by copy number gains in 11p. However, we have recently observed agminated presentations of fusion-driven melanocytic neoplasms.
We retrieved cases from our database of benign fusion-induced melanocytic neoplasms with an agminated presentation. Both the primary lesion and the secondary lesion were sequenced. TERT-promoter mutational testing and the melanoma fluorescence in situ hybridization assay were also performed.
Three cases were included. Two had a PRKCA fusion (partners ATP2B4 and MPZL1) and one had a ZCCHC8::ROS1 fusion. None of the cases met morphologic or molecular criteria for malignancy. There was no evidence of tumor progression in secondary lesions. The same fusion was identified in the primary and secondary lesions. None of the patients developed evidence of nodal or systemic metastasis.
We present accumulating evidence that fusion-driven melanocytic neoplasms can present with an agminated presentation. The differential diagnosis of an agminated presentation versus a locally recurrent or potentially locally metastatic tumor is critical, and accurate diagnosis has significant prognostic and therapeutic consequences for the patient. As with HRAS mutations, fusion-driven melanocytic tumors may have an agminated presentation.
聚集性 Spitz 痣的传统发病机制包括 HRAS 突变镶嵌体,随后是 11p 拷贝数增加。然而,我们最近观察到融合驱动的黑色素瘤具有聚集性表现。
我们从良性融合诱导黑色素瘤数据库中检索到具有聚集性表现的病例。对原发性病变和继发性病变均进行了测序。还进行了 TERT 启动子突变检测和黑色素瘤荧光原位杂交检测。
纳入 3 例。2 例存在 PRKCA 融合(伴侣 ATP2B4 和 MPZL1),1 例存在 ZCCHC8::ROS1 融合。没有任何病例符合恶性肿瘤的形态学或分子标准。继发性病变无肿瘤进展证据。原发性和继发性病变均发现相同的融合。所有患者均未出现淋巴结或全身转移的证据。
我们提供的越来越多的证据表明,融合驱动的黑色素瘤可能表现为聚集性。聚集性表现与局部复发性或潜在局部转移性肿瘤的鉴别诊断至关重要,准确诊断对患者具有重要的预后和治疗意义。与 HRAS 突变一样,融合驱动的黑色素瘤肿瘤可能具有聚集性表现。