Neuro-endocrine tumours of the lung. A review of relevant pathological and molecular data

Neuroendocrine (NE) tumours of the lung include pure and mixed forms. In the former group, a continuum of lesions is recognised ranging from benign typical carcinoids to atypical carcinoids (having a low-grade behaviour, although often associated with regional and distant metastases), to the highly aggressive poorly differentiated carcinomas of the small and large cell types. In the mixed tumour group, the NE component is extensively represented in association with any of the non-small cell carcinoma subtypes (so-called combined carcinomas), or the NE component is restricted to a cell population scattered among adenocarcinoma cells (or more rarely within squamous or large cell carcinomas). The molecular profile of NE tumours has been widely investigated to identify features helpful for the diagnosis, prognosis and even therapy for this special lung tumour category. Specific chromosomal alterations, oncogene mutations and cell cycle molecule disregulation has been documented in NE tumours of the lung, as well as the expression of specific receptors or enzymes implicated in the response to biotherapies or to chemotherapeutic agents. The 'molecular classification' of NE tumours should be integrated to morphology, for a better definition of the different histological types and a more appropriate selection of the therapeutic strategy.