Abstract：
The combination of neuroendocrine/non neuroendocrine lung tumors (CNNELT) mentioned in the last edition of the World Health Organization (WHO) of Thoracic Tumors refers to small cell carcinoma (SCLC) or large cell neuroendocrine carcinoma (LCNEC) mixed with any other non-small cell lung carcinoma (NSCLC). Typical Carcinoid (TC)/Atypical Carcinoid (AC) combined with NSCLC is not included among this category. However, case reports of TC/AC combined with NSCLC have been described. We previously reported 2 cases of lung adenocarcinoma (LUA) mixed with carcinoid sharing mutations in both components supporting the hypothesis of a clonal origin. We extended our analysis to other four cases of mixed NSCLC-carcinoid by performing targeted-DNA and RNA-based NGS analysis in both primary and their paired lymph nodes metastasis. In all cases, LUA and AC components shared at least 1 common mutation (KRAS driver mutation p.Gly12Val in cases 1 and 3, AKAP13-RET fusion in case 2, and missense KRAS driver mutation p.Gly12Ala in case 4, reinforcing the hypothesis of a clonal origin. Moreover, the same mutation was detected in the metastasis constituted only by AC (cases 2 and 4). Although it is a rare malignancy in the lung, mixed LUA and TC/AC could be included among the histotypes for which a deep molecular characterization of both components is needed to identify the presence of potential druggable genetic alterations.
摘要：
上一版世界卫生组织(WHO)胸部肿瘤中提到的神经内分泌/非神经内分泌肺肿瘤(CNNELT)的组合是指与任何其他非小细胞肺癌(NSCLC)混合的小细胞癌(SCLC)或大细胞神经内分泌癌(LCNEC)。与NSCLC组合的典型类癌(TC)/非典型类癌(AC)不包括在这一类别中。然而,已经描述了TC/AC合并NSCLC的病例报告。我们先前报道了2例肺腺癌（LUA）与两种成分中的类癌共享突变混合的病例，支持克隆起源的假设。我们通过在原发灶及其配对淋巴结转移中进行靶向DNA和基于RNA的NGS分析，将我们的分析扩展到其他四例混合NSCLC-类癌病例。在所有情况下,LUA和AC组件共享至少1个常见突变（病例1和3中的KRAS驱动突变p.Gly12Val，病例2中的AKAP13-RET融合，病例4中的错义KRAS驱动突变p.Gly12Ala，增强了克隆起源的假设。此外，在仅由AC构成的转移灶中检测到相同的突变（病例2和4）。虽然这是一种罕见的肺部恶性肿瘤，混合的LUA和TC/AC可以包括在需要对两种成分进行深入的分子表征的组织型中,以鉴定潜在的可药物遗传改变的存在。
