The cribriform pattern identifies a subset of acinar predominant tumors with poor prognosis in patients with stage I lung adenocarcinoma: a conceptual proposal to classify cribriform predominant tumors as a distinct histologic subtype

Abstract

The 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) lung adenocarcinoma classification emphasizes the prognostic significance of histologic subtypes. However, one limitation of this classification is that the highest percentage of patients (∼40%) is classified as acinar predominant tumors, and these patients display a spectrum of favorable and unfavorable clinical behaviors. We investigated whether the cribriform pattern can further stratify prognosis by histologic subtype. Tumor slides from 1038 patients with stage I lung adenocarcinoma (1995–2009) were reviewed. Tumors were classified according to the IASLC/ATS/ERS classification. The percentage of cribriform pattern was recorded, and the cribriform predominant subtype was considered as a subtype for analysis. The log-rank test was used to analyze the association between histologic variables and recurrence-free probability. The 5-year recurrence-free probability for patients with cribriform predominant tumors (n=46) was 70%. The recurrence-free probability for patients with cribriform predominant tumors was significantly lower than that for patients with acinar (5-year recurrence-free probability, 87%; P=0.002) or papillary predominant tumors (83%; P=0.020) but was comparable to that for patients with micropapillary (P=0.34) or solid predominant tumors (P=0.56). The recurrence-free probability for patients with ≥10% cribriform pattern tumors (n=214) was significantly lower (5-year recurrence-free probability, 73%) than that for patients with <10% cribriform pattern tumors (n=824; 84%; P<0.001). In multivariate analysis, patients with acinar predominant tumors with ≥10% cribriform pattern remained at significantly increased risk of recurrence compared with those with <10% cribriform pattern (P=0.042). Cribriform predominant tumors should be considered a distinct subtype with a high risk of recurrence, and presence (≥10%) of the cribriform pattern is an independent predictor of recurrence, identifying a poor prognostic subset of acinar predominant tumors. Our findings highlight the important prognostic value of comprehensive histologic subtyping and recording the percentage of each histologic pattern, according to the IASLC/ATS/ERS classification with the addition of the cribriform subtype.