Pathological Anatomy Unit, University Hospital of Padua, 35121 Padua, Italy.
Section of Anatomic Pathology, Department of Health Sciences, University of Florence, 50139 Florence, Italy.
Int J Mol Sci. 2021 Nov 15;22(22):12332. doi: 10.3390/ijms222212332.
Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the translocated), RNA-based NGS and real time RT-PCR were both positive in three cases, and FISH and real time RT-PCR in another two cases. In seven ASTs fusions were detected only by FISH and in two cases only by real time RT-PCR. The frequency of NTRK fusions in ASTs is 9%, with a clear prevalence of compared to alterations. Pan-TRK immunohistochemistry is an excellent screening test. Confirmation of fusions may require the use of different molecular techniques.
非典型 Spitz 肿瘤（AST）在一个或多个非典型特征上与典型 Spitz 痣不同，现在被认为是一种具有不确定恶性潜能的黑色素细胞肿瘤的中间类别。激活融合在 Spitz 病变中引发致癌事件，并可通过激酶抑制剂靶向治疗。然而，它们在 AST 中的普遍性以及检测它们的最佳方法尚未确定。用泛 TRK 免疫组化筛选了一系列 180 例 AST，并使用 FISH、两种不同的用于实体瘤的基于 RNA 的 NGS 面板和特定的实时 RT-PCR 面板证实了融合的存在。总体而言，有 26 例 AST 显示泛 TRK 免疫染色。在这些病例中，有 15 例显示细胞质免疫反应，有 融合，而有 1 例显示核免疫反应。只有在 2 例 AST 中，分子检测结果均为阳性（包括易位），基于 RNA 的 NGS 和实时 RT-PCR 在 3 例中均为阳性，FISH 和实时 RT-PCR 在另 2 例中为阳性。在 7 例 AST 中，融合仅通过 FISH 检测到，在 2 例中仅通过实时 RT-PCR 检测到。AST 中 NTRK 融合的频率为 9%，与 改变相比，明显更常见。泛 TRK 免疫组化是一种出色的筛选试验。融合的确认可能需要使用不同的分子技术。
