Cribriform and fused glands are patterns of high-grade pulmonary adenocarcinoma

The 2011 International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society classification of pulmonary adenocarcinoma recognizes the prognostic significance of different histologic patterns but does not address the issue of tumor grade. We previously developed an objective and prognostic grading system for pulmonary adenocarcinomas that is based on associating patterns with their metastatic potential. The best prognostic stratification was achieved by summing the grades of the 2 most predominant patterns (histologic score). Here, we extend this work by evaluating the prognostic importance of variant patterns of adenocarcinoma, which are not recognized by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Pathologic specimens from 249 resected stage I adenocarcinomas were reviewed. The proportions of standard and nonstandard patterns (cribriform and fused glands) were recorded for each case. The associations between the presence of standard and nonstandard patterns, tumor histologic score, and disease-free survival were evaluated. Cribriform and fused gland patterns were observed in 15% and 29% of tumors, respectively. These nonstandard patterns each composed 10% to 100% of the entire tumors but were the predominant pattern in only 5% and 7% of tumors, respectively. The presence of complex glandular patterns was associated with solid pattern (P < .001) and high histologic score (P < .0001). Disease-free survival for tumors with predominant complex glandular patterns was similar to that for high-grade tumors (P = .932) and was significantly worse than that for low- and intermediate-grade tumors (P = .0025). Complex glandular patterns have a significant prognostic value and should be considered patterns of high-grade adenocarcinoma.