Epidemiology of Non-gastroenteropancreatic (Neuro)Endocrine Tumours
Summary and Introduction
The widespread availability and reliability of immunohistochemical techniques in the last three decades have allowed researchers to identify cells with common neuroendocrine markers in virtually every organ. As a whole, these neuroendocrine cells form the so-called diffuse neuroendocrine system. Tumours arising from the cells of the diffuse neuroendocrine system are defined as (neuro)endocrine tumours (NETs). NETs have been increasingly described in recent years. However, despite the increase in the number of published papers focused on NET, we still lack adequate epidemiological data, particularly for non-gastroenteropancreatic (GEP) NETs. Furthermore, the real incidence of neuroendocrine differentiation for most sites is not completely known and is probably underestimated. As a consequence, data on the clinical features of many NET subgroups are not well known or confusing. For all of these reasons, we have attempted to evaluate the epidemiology of non-GEP NETs, reviewing the limited data available in the literature.
Despite the substantial and progressive increase in published data since the first description at the end of the 19th century, we are still lacking adequate epidemiological information on (neuro)endocrine tumours (NETs), particularly for non-gastroenteropancreatic (GEP) NETs. This is probably a consequence of rarity, frequent lack of associated clinical signs, a multidisciplinary setting of occurrence, and the continuous evolution of diagnostic techniques and classification criteria. Contrary to other solid tumours, mortality cannot be used as an approximation of incidence and prevalence because they generally respond well to surgical treatment; furthermore, the well-differentiated NET is usually characterized by indolent behaviour. The histological definition of NET has been markedly improved in the last three decades by the wide availability of immunohistochemical techniques and by the formulation of valuable unified criteria, regardless the site of origin of the tumour. Moreover, current opinion postulates that neuroendocrine cells may have different embryological origins and are widely dispersed around the body, not only limited to the gastrointestinal tract, but also within the lungs, larynx, thymus, thyroid, adrenal, gonads, skin and many other organs and tissues. As a whole, these neuroendocrine cell aggregates dispersed in non-neuroendocrine tissues constitute the diffuse neuroendocrine system.
Apart from the GEP location, most of the published data on the epidemiology and clinical presentation of NETs are still scarce and generally limited to case reports or small series, where the real incidence of neuroendocrine differentiation for most sites is not completely known and probably underestimated. A further factor that limits the achievement of 'real' epidemiological data is the discrepancy between the estimated incidence of GEP NETs, around one case per million per year and the higher prevalence of these tumours found in autopsy series. In this study, we attempt to collect data available from the literature on the epidemiology of non-GEP NETs, arising from neuroendocrine cells dispersed in the lung, larynx, thymus, genital tract and skin. Organ-specific NETs such as those arising in the thyroid, pituitary and parathyroid are not included in this review due to their site-specific peculiarities.