Epidemiological studies on neuroendocrine tumours (NETs) generally show a major increase in incidence. To investigate this increase, epidemiological data from the Netherlands were evaluated according to histological grade.

All 47,800 patients with NET (diagnosed 1990-2010) from the population-based Netherlands Cancer Registry were stratified according to the latest World Health Organization (WHO) classification for the digestive system: well-differentiated NET grade 1 and 2 (G1NET and G2NET), and poorly differentiated (grade 3) neuroendocrine carcinoma, subdivided into large cell (G3-LCNEC) and small cell (G3-SCNEC).

The age-standardised incidence rate (excluding G3-SCNEC) increased from 2.1/100,000 in 1990 to 4.9/100,000 in 2010. The incidence of G1NET increased from 2.0 to 3.0; there was a large increase in G2NET from 0.01 in 1990 to 0.2 in 2010, and of the G3-LCNEC from 0.01 to 1.8, respectively. In G3-SCNEC incidence in men decreased from 21.3 to 10.1, whereas in women it increased from 4.5 to 7.7. The 5-year survival improved in G1NET, particularly for metastatic disease, from 30% in 1990-2000 to 47% in 2001-2010.

The increasing incidence of NET (without G3-SCNEC) was mainly due to the increase of G3-LCNEC. This increase is related to improved diagnostic procedures and to shifting in pathology from other entities (such as undifferentiated carcinoma) to NET. Improved survival was seen in all sites and stages, especially in patients with metastatic G1NET. Because of its influence on incidence and survival, we recommend to present epidemiological studies on NET according to histological classification.