Institute of Pathology, University Medical Centre Mannheim and Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Department of Neurology, University of Regensburg, Regensburg, Germany.
Virchows Arch. 2021 Jan;478(1):101-110. doi: 10.1007/s00428-021-03068-8. Epub 2021 Mar 5.
Thymomas exhibit a unique genomic landscape, comprising the lowest on average total mutational burden among adult human cancers; a unique point mutation in the GTF2I gene in WHO type A and AB thymomas (and rarely others); almost unique KMT2A-MAML2 translocations in rare WHO type B2 and B3 thymomas; a unique YAP1-MAML2 translocation in almost all metaplastic thymomas; and unique miRNA profiles in relation to GTF2I mutational status and WHO histotypes. While most thymomas can be diagnosed solely on the basis of morphological features, mutational analyses can solve challenging differential diagnostic problems. No molecular biomarkers have been identified that predict the response of unresectable thymomas to chemotherapy or agents with known molecular targets. Despite the common and strong expression of PDL1 in thymomas, immune checkpoint inhibitors are rarely applicable due to the poor predictability of common, life-threatening autoimmune side effects that are related to the unrivaled propensity of thymomas towards autoimmunity.
胸腺瘤表现出独特的基因组特征，其平均总突变负担在成人癌症中最低；在 WHO 分型 A 和 AB 胸腺瘤中存在 GTF2I 基因的独特点突变（其他类型罕见）；在罕见的 WHO 分型 B2 和 B3 胸腺瘤中存在几乎独特的 KMT2A-MAML2 易位；在几乎所有的间变性胸腺瘤中存在独特的 YAP1-MAML2 易位；以及与 GTF2I 突变状态和 WHO 组织学类型相关的独特 miRNA 谱。虽然大多数胸腺瘤仅基于形态学特征即可诊断，但突变分析可以解决具有挑战性的鉴别诊断问题。目前尚未确定预测不可切除胸腺瘤对化疗或具有已知分子靶点药物反应的分子生物标志物。尽管胸腺瘤中普遍且强烈表达 PD-L1，但由于与胸腺瘤自身免疫倾向相关的常见、危及生命的自身免疫性副作用的可预测性较差，免疫检查点抑制剂很少适用。
