Pulmonary enteric adenocarcinoma: a study of the clinicopathologic and molecular status of nine cases

Abstract

Pulmonary enteric adenocarcinoma (PEAC), a extremely rare variant of primary invasive adenocarcinoma of the lung, was recognized by the international multidisciplinary classification of lung adenocarcinoma which was proposed by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) published in early 2011. Histologically, PEAC is considered to be mainly composed of tall columnar cells arranged in an irregular glandular cavity or cribriform pattern with extensive central necrosis which show high resemblance to that of intestinal epithelia and colorectal carcinomas. Immunohistochemically, PEAC can not only expresses typical proteins common to lung primaries but is positive for at least one intestinal markers, such as CDX2, cytokeratin (CK) 20, MUC2, therefore, the differentiation of primary PEACs from metastatic colorectal cancers can be challenging. In this study, we report 9 cases of PEAC and a panel of immunohistochemical protein markers of CK7, CK20, thyroid transcription factor 1 (TTF-1), Napsin A, MUC2 and villin was analyzed with the comparison of 20 metastatic colorectal carcinomas (MCRs), and 20 typical primary adenocarcinomas (tPACs). As was expected, CK7 expression was documented in all 9 PEACs and 20 tPCAs while CK20 was significantly more prevalent in adenocarcinoma that originated from colorectal. Additionally, we evaluate the classical mutations of EGFR, KRAS in the 9 cases of PEACs, it turned out that all tumors were EGFR-wild and KRAS-wild types, which confirmed that PEAC has a separate phenotype from usual pulmonary adenocarcinoma.

Keywords: EGFR/KRAS mutations; Pulmonary adenocarcinoma; clinicopathologic features; enteric; immunohistochemistry.

Figure 1

Histological features. A: Glands are medium-to-large sized, with lumina filled with extensive nuclear and cellular debris resulting in “dirty necrosis” (HE, ×200). B: Unlike MCRs, which are largely monotonous in histology, pulmonary enteric adenocarcinoma exhibits heterogeneous features, such as cribriform growth pattern (HE, ×100). C: Tall-columnar tumor cells with eosinophilic cytoplasm and tall or ovoid nuclei. Nuclei arrange in a palisading or pseudostratified pattern (HE, ×400).

Figure 2

Pulmonary enteric adenocarcinoma (PEAC) exhibit characteristic immunohistochemical features. A-F: It can show immunoreactivity for CK7 (A: Case 2), TTF-1 (B: Case 3), napsin A (C: Case 4), CDX2 (D: Case 8), MUC2 (E: Case 6) and villin (F: Case 5). G: Most PEAC are CK20 negative (case 2).