在先前的研究中，发现儿童黄色肉芽肿（JXG）和成人黄色肉芽肿（AXG）中存在相互排斥的驱动基因，包括MAP激酶通路基因的突变，如MAP2K1，BRAF，ARAF，KRAS，NRAS，PIK3CD，以及BRAF和ALK的融合。此外还有一些未明确驱动基因的病例，罕见病例中出现了NTRK融合。我们通过下一代测序（NGS）鉴定了两个连续的局部JXG或AXG，并通过泛-NTRK免疫染色进行了确认。我们将研究扩大到了50例JXG和AXG的病例，通过泛-NTRK免疫染色进行筛查。通过NGS在5例组织细胞肿瘤没有NTRK融合的病例以及14例非肿瘤的组织细胞疾病中验证了我们方法的特异性。我们发现了23例JXG或AXG表达了过多的NTRK，在这些病例中，限于局部疾病（43例中的23例，53.5%），而不是广泛扩散性疾病（7例中的零例）。NTRK表达在JXG或AXG中普遍存在，并与局部疾病相关。我们推测，之前忽视了这一点的重要性，可能是因为倾向于对广泛扩散性疾病进行测序研究。我们通过NGS确认了两个阳性病例中的NTRK1融合的存在，然而，还需要进一步进行基因研究来进一步探索这一点。 © 2023 The Authors. 由约翰·威利和儿子有限公司出版的《皮肤病学杂志》发布。

Previously identified mutually-exclusive driver genes in juvenile xanthogranuloma (JXG) and adult xanthogranuloma (AXG) include mutations in MAP kinase pathway genes such as MAP2K1, BRAF, ARAF, KRAS, NRAS, PIK3CD as well as fusions in BRAF and ALK, with a subset of cases with no identified driver yet. NTRK fusion has been identified in rare cases.We identified two consecutive index cases of localized JXG or AXG with NTRK1 fusion by next-generation sequencing (NGS) and confirmed by pan-NTRK immunostain. We expanded the study to a total of 50 cases of JXG and AXG using screening by pan-NTRK immunostain. We confirmed the specificity of our approach with negative results in 5 cases of histiocytic neoplasia lacking an NTRK fusion by NGS and 14 cases of non-neoplastic histiocytic disease.We found 23 cases of JXG or AXG with overexpression of NTRK by immunostain, and these cases were restricted to localized disease (23 of 43 cases, 53.5%) rather than disseminated disease (zero of seven cases).NTRK expression is common in JXG or AXG and associated with localized rather than disseminated disease. We speculate that the potential importance of this in JXG and AXG has not been previously appreciated due to the tendency to focus sequencing studies on disseminated disease. We confirm the presence of an NTRK1 fusion in two positive cases by NGS, however, additional genetic studies are necessary to further explore this.© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.