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Ciliated Muconodular Papillary Tumors of the Lung Can Occur in Western Patients and Show Mutations in BRAF and AKT1.

发生在西方患者的肺纤毛黏液结节性乳头状肿瘤具有BRAF 和AKT1突变

Liu L,Aesif SW,Kipp BR,Voss JS,Daniel S,Aubry MC,Boland JM

Abstract

Ciliated muconodular papillary tumors (CMPTs) are rare peripheral lung lesions, characterized by papillary architecture and ciliated columnar cells admixed with mucinous cells and basal cells. They often have prominent surrounding intra-alveolar mucin, which can lead to diagnostic confusion with mucinous adenocarcinoma. Recognition of the ciliated component is the key to diagnosis of CMPT. The literature contains few reported cases to date, all occurring in East-Asian patients. Although follow-up data are limited, CMPT seems to be an indolent tumor with very good prognosis, leading some to question whether it is a reactive or hamartomatous lesion. However, a very recent molecular study has identified BRAF (40%) and EGFR (30%) alterations in CMPT, supporting a truly neoplastic process. Here for the first time, we report 4 cases of morphologically typical CMPT in western patients, occurring in 1 man (60 y) and 3 women (71 to 83 y). Interestingly, 1 case occurred in background of pronounced small airway disease with necrotizing bronchiolitis and multiple carcinoid tumorlets. We further analyzed 1 tumor using a 50 gene next-generation sequencing oncology panel that identified 2 pathogenic mutations (BRAF V600E and AKT1 E17K). Our study is the first to describe that CMPT can occur in western (non-Asian) patients. Our data confirm BRAF V600E mutation as a probable driver in a subset of these tumors, along with AKT1 mutation, which further supports that CMPT are indolent pulmonary neoplasms.

摘要

纤毛黏液结节性乳头状肿瘤(CMPTs)是一种罕见的肺外周病变,以乳头状结构和纤毛柱状细胞与粘液细胞、基底细胞混合为特征。常出现显著的肺泡腔内黏液,可能导致与黏液腺癌诊断上的混淆。诊断CMPT的关键在于对具有纤毛柱状细胞的识别。目前文献报道较少,且均发生于东亚患者。尽管随访资料有限,但是CMPT是一种惰性肿瘤,预后较好。因此有学者质疑其是否为一种反应性或错构瘤性病变。然而,最近的分子研究证实了CMPT中存在BRAF40%)和EGFR基因(30%)突变,支持其是真正的肿瘤性病变。

本文作者首次报道4例发生在西方患者中、具有典型形态学特征的CMPT,男性1例(60岁),女性3例(71-83岁)。有趣的是,其中1例发生在背景有明显小气道病变的坏死性细支气管炎和多灶性微小类癌的患者。通过新一代测序技术进一步分析其中一个肿瘤中的50个基因突变情况,发现存在BRAF V600EAKT1 E17K突变。本研究首次报道了发生在西方患者(非亚洲人)中的CMPT,且证实了BRAF V600E突变很有可能是该肿瘤发生的一个驱动因素,并伴有AKT1基因突变,进一步支持CMPT是一种惰性的肺肿瘤。

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