Grading the neuroendocrine tumors of the lung: an evidence-based proposal

Bronchial NETs are separated in to 4 categories by the WHO 2004 classification. These are typical carcinoids, atypical carcinoids, small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma. The WHO 2004 classification does not include Ki67 proliferation assessment. The WHO 2010 classification of digestive NETS is based in part on Ki67 proliferation assessment and has been proven to be prognostically significant. This study compares the two classification systems and defining a prognostic grading system for lung neuroendocrine tumors.

The study included 399 patients who underwent surgery and with at least 1 year follow-up between 1989 and 2011. Data on 21 variables were collected, and performance of grading systems and their components was compared by Cox regression and multivariable analyses. All statistical tests were two-sided. At Cox analysis, WHO 2004 stratified patients into three major groups with statistically significant survival difference (typical carcinoid vs, atypical carcinoid (AC), P=0.021; AC vs large-cell/small-cell lung neuroendocrine carcinomas, P<0.001). Optimal discrimination in three groups was observed by Ki67% (Ki67% cutoffs: G1 <4, G2 4–<25, G3 ≥25; G1 vs G2, P=0.021; and G2 vs G3, P≤0.001), mitotic count (G1 ≤2, G2 >2–47, G3 >47; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001), and presence of necrosis (G1 absent, G2 <10% of sample, G3 >10% of sample; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001) at uni- and multivariable analyses. The combination of these three variables resulted in a simple and effective grading system.

In conclusion, a three-tier grading system based on Ki67 index, mitotic count, and necrosis with cutoffs specifically generated for lung neuroendocrine tumors is prognostically effective and accurate.

Source: Endocrine-Related Cancer