Carcinoids of the lung caused by exogenous noxious agents: a scoping review

Approximately 2% of lung tumours are pulmonary carcinoids (PCs), divided into typical (90%) and atypical (AC) (10%). The link with external exposure to carcinogens remains controversial.

To investigate the association between occupational exposure to carcinogens and PC tumours.

A PRISMA-ScR-guided scoping review was performed. A systematic search was conducted in PubMed and Embase (January 2025). Studies were reviewed, data extracted, analysed and summarised narratively.

1302 studies were reviewed. 27 original studies and seven conference papers on topics including exposure to cigarette smoke (n=23) and asbestos (n=6), or mechanistic information, were included. Following the collapse of the World Trade Center in 2001, carcinoids accounted for 6% of lung cancer cases in people exposed to the resulting dust (9% in women, 3% in men). The proportion of ACs among carcinoids rose from 9.3% (controls) to 16.3% (smokers) and from ∼25% to 45% (probable versus definite asbestos exposure). Basic research has identified biological pathways linking harmful exposures (such as asbestos and cigarette smoke) to neuroendocrine cell proliferation and the potential progression of PCs to higher-grade lung tumours.

The significance these of findings is limited due to 1) the limited number of studies, 2) the small number of tumours within those studies and 3) the lack of rigid diagnostic (morphological and molecular) criteria for PCs in most studies. Nevertheless, a consistent finding is a higher proportion of AC among carcinoids, particularly following asbestos exposure.

Based on these findings, a link between carcinogenic substances (especially asbestos and cigarette smoke) and carcinoids seems plausible. More stringent analyses in epidemiological surveys are needed to further clarify the pathogenesis of PCs.