Mixed/combined pulmonary non-small cell carcinoma and carcinoid: State-of-the-Art review of clinical, histological, and molecular features with therapeutic implications

: Mixed neuroendocrine-non-neuroendocrine neoplasms are well-known entities and are codified as separate classes in the WHO classification of different organs and systems. In particular, combined low-grade neuroendocrine neoplasms-such as neuroendocrine tumors (NETs) in the gastrointestinal system and carcinoid in the lung-and non-neuroendocrine neoplasms are peculiar entities for both their origin and clinical significance. Combined NETs and non-neuroendocrine neoplasms were introduced in the WHO classification of digestive tumors several years ago, whilst combined carcinoid (both typical and atypical) and non-small cell lung cancer is an unrecognized identity. However, case reports and series of combined carcinoid and non-small cell lung cancer have been described in the literature, with morphological, biological, and clinical details supporting the hypothesis of a well-defined identity. In this paper, we aim to summarize all cases of combined carcinoid and non-small cell lung cancer, focusing on clinical, morphological, and biological features, suggesting the need to recognize and include this entity as a separate class, in particular for its distinct therapeutic implications.