Pulmonary Adenocarcinoma with Enteric Differentiation: Immunohistochemistry and Molecular Morphology

Pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare subtype of lung adenocarcinoma recently recognized in the WHO classification. It is defined as an adenocarcinoma in which the enteric component exceeds 50% and have to show the expression of at least 1 immunohistochemical marker of enteric differentiation. Although the definition of this tumor type is very important, above all in the differential diagnosis between a primary lung tumor and a metastasis of colorectal adenocarcinoma, this cancer still lacks a distinctive immunohistochemical and molecular signature. We recruited the largest series in the literature of PAEDs according to the morphology and the positivity for intestinal markers. Then, we evaluated the immunohistochemical and molecular profile of these adenocarcinomas. In our series, CDX-2 and CK7 were the immunohistochemical markers mostly expressed by PAEDs. There was an inverse relationship between the expression of pnuemocytes markers, such as TTF-1, and intestinal markers. Molecular analysis revealed KRAS as the most frequently mutated gene (>60% of cases), with very few cases harboring abnormalities affecting EGFR, BRAF, and ALK genes. PAEDs are morphologically very heterogenous. The immunohistochemical profile based on CDX-2 and CK7 positivity of PAEDs appears very robust to support this diagnosis, and it is applicable also on small biopsies. KRAS appears as the most important mutated gene in such tumors.