Cribriform adenocarcinoma of the lung: clinicopathologic, immunohistochemical, and molecular analysis of 15 cases of a distinctive morphologic subtype of lung adenocarcinoma

• Published in: Modern pathology Vol. 27; no. 8; pp. 1063 - 1072
• Main Authors: Mackinnon, Alexander C, Luevano, Arturo, de Araujo, Lisley C, Rao, Nagarjun, Le, Min, Suster, Saul
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.08.2014; Nature Publishing Group US; Elsevier Limited
• Subjects: 631/1647/1513; 631/1647/664/1257; 692/699/67/1612; 692/700/139/422; Activin Receptors, Type II - genetics; Adenocarcinoma - chemistry; Adenocarcinoma - classification; Adenocarcinoma - diagnosis; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; ALK1; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Cancer therapies; Classification; cribriform adenocarcinoma; Diagnosis, Differential; DNA Mutational Analysis; ErbB Receptors - genetics; Female; Gene Rearrangement; Genes; Genetic Predisposition to Disease; Histology; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Kinases; KRAS; Laboratory Medicine; lung adenocarcinoma; Lung cancer; Lung Neoplasms - chemistry; Lung Neoplasms - classification; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical schools; Medicine; Medicine & Public Health; metastases to the lungs; Metastasis; Middle Aged; molecular diagnostics; Mutation; original-article; Pathology; Phenotype; Predictive Value of Tests; Prostate; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Retrospective Studies; ROS1; Tumors; United States > US; Ohio; Wisconsin; molecular diagnostics; cribriform adenocarcinoma; lung adenocarcinoma; KRAS; metastases to the lungs; ROS1; ALK1
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.2013.227

Lung adenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary, solid, and lepidic (bronchioloalveolar). Tumors displaying a prominent or predominant cribriform architecture are rare and most often confused for metastases from other organs. We report the clinical, histologic, immunohistochemical, and molecular features in 15 primary lung adenocarcinomas with a predominant cribriform histology. All patients were adults between 30 and 80 years of age (median: 64), and all but one reported a history of heavy cigarette smoking. All cases showed a predominant (>70%) cribriform architecture that resembled a variety of tumors arising in other organs, including breast, prostate, ovary, pancreas, uterus, colon, and thyroid. Immunohistochemical stains showed a phenotype consistent with a primary lung tumor (ie, TTF1+/CK7+), with negative results for other markers. Molecular analysis in six cases showed that none harbored an EGFR-activating mutation. KRAS mutation was detected in one case, and an ALK1 and ROS1 gene rearrangement were each detected in an additional two cases. Cribriform adenocarcinomas of the lung represent a distinctive histologic subtype of lung cancer that may be morphologically difficult to differentiate from metastases with a predominant cribriform architecture.