在Spitz肿瘤中已经证明了许多标志性的遗传改变,最值得注意的是激酶基因的融合(包括BRAF,ALK,ROS1,NTRK1,NTRK3,RET,MET,MAP3K8)或HRAS中的变体。虽然在Spitz肿瘤中有多个涉及NTRK1和NTRK3的重排的报道,文献中关于NTRK2重排的Spitz痣的报道很少。本报告介绍了NTRK2重排的非典型Spitz肿瘤,具有纺锤状细胞特征。患者是一名6岁的女性,背部有色素沉着的丘疹。组织病理学评估显示不对称,双相,黑素细胞的复合增殖,其特征是上皮样细胞群排列为不同大小的巢和沿基底层向下延伸的单个细胞,以及一群具有促纤维化特征和真皮中Melan-A表达丧失的纺锤状黑素细胞。表皮组件中p16表达的部分损失和真皮组件中的扩散损失。PRAME的免疫组织化学,ALK,NTRK1,HRASQ61R,p53和BRAFV600E均为阴性。通过RNA测序鉴定SQSTM1::NTRK2融合物。没有检测到TERT启动子热点变体。此病例报告扩展了Spitz肿瘤遗传改变的已知组织病理学谱。
A host of signature genetic alterations have been demonstrated in Spitz neoplasms, most notably fusions of kinase genes (including BRAF, ALK, ROS1, NTRK1, NTRK3, RET, MET, MAP3K8) or variants in HRAS. While there are multiple
reports of rearrangements involving NTRK1 and NTRK3 in Spitz tumors, there are very few
reports of NTRK2-rearranged Spitz nevi in the literature. This report presents an NTRK2-rearranged atypical Spitz tumor with spindled cell features. The patient was a 6-year-old female with a growing pigmented papule on the back. Histopathological evaluation revealed an asymmetric, biphasic, compound proliferation of melanocytes featuring an epithelioid cell population arranged as variably sized nests and single cells along the basal layer with extension down adnexa, as well as a population of spindled melanocytes with desmoplastic features and loss of Melan-A expression in the dermis. There was partial loss of p16 expression in the epidermal component and diffuse loss in the dermal component. Immunohistochemistry for PRAME, ALK, NTRK1, HRAS Q61R, p53, and BRAF V600E were negative. A SQSTM1::NTRK2 fusion was identified by RNA sequencing. No TERT promoter hotspot variants were detected. This
case report expands the known histopathologic spectrum of genetic alterations in Spitz neoplasms.