Prognostic Factors: Grading (Ki-67 Index)

Abstract

While Ki-67 index is crucial for the diagnosis and grading and for prognostic and predictive purposes in digestive neuroendocrine tumors (NET), it does not play the same established role in lung NET. In fact, gastroenteropancreatic NE neoplasms are classified into two groups of NET and NE carcinomas, both of them further graded into G1, G2, and G3. The assumption that all G3 neoplasms are NE carcinomas by definition has been recently challenged by the identification of a new category of well-differentiated G3 tumors, named NET G3, based on the organoid architecture but a high proliferative activity (Ki-67 ranging 20–40%). Conversely, tumor grading in lung NET is defined by the histological classification based on mitotic count and necrosis, identifying typical carcinoids (low-grade), atypical carcinoids (intermediate-grade), large cell NE carcinomas, and small cell lung carcinomas (high-grade malignancies). Although Ki-67 index is not a diagnostic parameter, proposals were made to combine mitoses, necrosis, and Ki-67 index to grade lung NET in a system significantly correlated with survival. The presently reported patient exemplifies a rare case classified as atypical carcinoid of the lung with a relatively high Ki-67 index (16%). The patient refused any further treatment after surgery despite the mitotic count at the upper limit of the category, foci of necrosis, and the intermediate Ki-67 count. Additional data are needed on well-differentiated lung NET displaying a relatively high proliferative activity that parallel the novel category of NET G3 of the digestive tract and that might require a therapeutic strategy different from the current postsurgical «wait and see» approach.