Recent updates on grading and classification of neuroendocrine tumors

•Gastroenteropancreatic neuroendocrine tumors are classified as grade 1, 2 and 3.•Grading is based on the mitotic count and Ki-67 labeling index.•Grade 3 tumors divided into well and poorly differentiated based on Ki-67 index.•Manual counting of printed images is the most reproducible way to measuring Ki-67.•Ki-67 labeling index is important in differential diagnosis of lung carcinoids.

Neuroendocrine tumors (NETs) are originating from neuroendocrine cells in diffuse endocrine systems. NETs are diagnosed by characteristic histologic features and immunoprofiles. Recent 2010 WHO classification for gastroenteropancreatic NETs introduced grading system based on mitotic count and Ki-67 proliferation index. Gastroenteropancreatic NETs are classified as NET grade 1, NET grade 2, and neuroendocrine carcinoma (NET grade 3). However, the carcinoid is still used in classification of NETs of the lung and uterine cervix. Some issues with grading system such as methodologies for evaluation of Ki-67 index and subclassification of neuroendocrine carcinoma (NET grade 3) are arising. The importance of Ki-67 labeling index is emerging in differential diagnosis of lung carcinoids. In this review, we focus on recent grading and classification of NETs and related issues in various organs, including gastrointestinal tract, pancreas, lung, and female reproductive organs.