Clinicopathological and genetic analyses of pulmonary enteric adenocarcinoma

Abstract

AimsPulmonary enteric adenocarcinoma (PEAC) is a rare variant of pulmonary adenocarcinoma. Due to its rarity, few pathological and molecular studies have been performed on PEAC. We herein conducted clinicopathological, immunohistochemical and molecular analyses of PEAC with a focus on its differentiation from invasive mucinous adenocarcinoma (IMA).MethodsWe examined the clinicopathological features of 16 cases of PEAC and performed a genetic analysis using next-generation sequencing (NGS). The results obtained were compared with those for IMA.ResultsThe average age of patients with PEAC (seven men and nine women) was 72.9 years. A comparison of clinical data on PEAC and IMA revealed no significant differences in age, sex or smoking history. Fifteen PEAC cases had dirty necrosis. Immunohistochemically, the positive rates for each antibody in PEAC were as follows: CK7, 88% (14/16); CK20, 81% (13/16); CDX2, 88% (14/16); p53, 69% (11/16); MUC1, 100% (16/16); MUC2, 19% (3/16); MUC5AC, 69% (11/16); MUC6, 19% (3/16). The positive rates for these antibodies in IMA were 100%, 87%, 0%, 7%, 93%, 0%, 100% and 80%, respectively.EGFRmutations, theMETexon 14 skipping mutation,BRAFmutations, theALKfusion gene andROS-1fusion gene were not detected in any cases of PEAC or IMA. Among PEAC cases, NGS identifiedKRASmutations in seven (44%, 7/16) andTP53mutations in nine (56%, 9/16). Among IMA cases, the most commonly mutated gene wasKRAS(90%).ConclusionsThe rates of dirty necrosis, immunopositivity for CDX2 andTP53mutations were significantly higher, while that ofKRASmutations was significantly lower in PEAC cases than in IMA cases.

Deciphering Lung Adenocarcinoma Heterogeneity: An Overview of Pathological and Clinical Features of Rare Subtypes

“…The overall PEAC prevalence accounts for 0.5% of all NSCLC cases [ 12 , 13 ]. The age of presentation is generally between 50 and 60 years and patients usually present more advanced disease at diagnosis compared to those affected by CLA, although some cases with early-stage disease have been described [ 14 ].…”

“…The first hypothesis, as put forward by Satoh et al [ 17 ], is based on the presence of common cancer stem cells in the lower respiratory tract and gastrointestinal mucosa, including goblet cells, Paneth cells and neuroendocrine cells. The role of smoking is still controversial [ 15 , 17 ], with some studies showing no differences in terms of smoking status between PEAC and primary lung adenocarcinoma [ 12 , 13 ].…”

“…Based on the 2021 WHO classification, PEAC is defined as a lung adenocarcinoma with enteric differentiation (>50%) that is mainly characterized by tall columnar cells with an eosinophilic cytoplasm that can display an acinar, cribriform or papillary architecture [ 13 , 23 ] ( Figure 2 ). Some glands may contain necrotic material defined as “Dirty Necrosis”.…”

“…Thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK-7) and napsin-A (an aspartic protease expressed by the cell surface of type II pneumocytes) are the most common immunohistochemistry assay targets used to identify a lung origin, while CDX-2, CK-20 and villin can be used to identify an enteric origin [ 16 ]. CDX-2 is usually expressed in 75–80% of cases; the lung markers CK-7 and napsin-A are expressed in 90% and 84% of cases, respectively [ 25 ]; TTF-1 shows low expression, although the sensitivity and specificity evidence is poor [ 13 , 23 ]. SATB-2 and beta-catenin have been recently discovered as further potential markers [ 15 ].…”

Lymph node and bone metastasis of pulmonary intestinal adenocarcinoma: A case report

“…Previous studies have identified smoking as a predisposing factor for PEAC, and the WNT-SOX2 signaling regulation pathway is over-activated under the stimulation of smoking and other factors, which may lead to intestinal metaplasia of airway basal cells. However, a recent study suggested that smoking may not be an important risk factor for the development of PEAC ( 23 ). In addition, several studies have shown that males are more likely to have PEAC, while other studies have come to the opposite conclusion ( 24 ).…”