A Grading System for Invasive Pulmonary Adenocarcinoma: A Proposal From the International Association for the Study of Lung Cancer Pathology Committee

Abstract

Introduction: A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of histologic criteria associated with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma.

Methods: A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histologic features associated with patient outcomes (recurrence-free survival [RFS] and overall survival [OS]). Receiver operating characteristic curve analysis was used to select the best model, which was validated (n = 212) and tested (n = 300, including stage I-III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics.

Results: The best model (area under the receiver operating characteristic curve [AUC] = 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histologic pattern with a cutoff of 20% for the latter. The model consists of the following: grade 1, lepidic predominant tumor; grade 2, acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and grade 3, any tumor with 20% or more of high-grade patterns (solid, micropapillary, or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC = 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Interobserver reproducibility revealed good agreement (k = 0.617).

Conclusions: A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma.

Keywords: Adenocarcinoma; Lung; Model; Prognosis; Tumor grading.

Figure 1.

Histologic examples of complex glandular patterns. (A) Cribriform pattern characterized by nests of neoplastic cells with sieve-like perforations; (B) poorly formed glands in a continuous spectrum between solid and acinar patterns; (C) fused and irregular glands in desmoplastic stroma; (D–F) poorly formed glands in a ribbon-like formation with irregular borders, small cell clusters, and single cells infiltrating desmoplastic stroma.

Figure 2.

Kaplan-Meier curves for RFS of the test cohort stratified by the IASLC grading system (A: the entire cohort and C: stage I cohort) and predominant pattern-based grading system (B: the entire cohort and D: stage I cohort). For the latter, grade 1 is composed of lepidic predominant tumors; grade 2 of acinar and papillary predominant tumors, and grade 3 of solid, micropapillary, and complex glandular predominant tumors. IASLC, International Association for the Study of Lung Cancer; RFS, recurrence-free survival.