Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops

Abstract

Background: Small intestinal neuroendocrine tumors are the most common of small bowel malignancies with a clinical incidence of about 1 per 100,000 persons per year. There has been a threefold increase in the incidence of small intestinal neuroendocrine tumor during later decades, but there are no studies that clarify whether this is due to a true higher incidence or if the rise is a mere product of, for instance, improved diagnostic modalities. The aim of this study was to investigate the incidence of clinical as well as subclinical small intestinal neuroendocrine tumors found at autopsy as well as describing the frequency of concomitant malignancies in patients with small intestinal neuroendocrine tumor. Materials and methods: An autopsy registry from the Malmö county population from 1970 to 1982 with an 87% autopsy rate was used. The clinical autopsy reports for patients coded for the existence of “carcinoid tumor” were scrutinized for the presence of small intestinal neuroendocrine tumor, metastatic disease, and concomitant malignancies. Details of patients with clinically diagnosed small intestinal neuroendocrine tumor during this time period were gathered from the Swedish Cancer Registry. Results: The mean annual incidence of small intestinal neuroendocrine tumor during this period was 5.33 per 100,000 individuals, and the mean annual prevalence was 581 per 100,000. The cause of death in the majority of cases was not due to small intestinal neuroendocrine tumor. In total, 48% of the people with small intestinal neuroendocrine tumor had at least one other malignancy, most commonly colorectal cancer. Conclusion: Most small intestinal neuroendocrine tumors are subclinical, and persons living with them will often die due to other causes. There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease. Moreover, a comparably high rate of associated colorectal carcinoma was found.

Incidence and survival of neuroendocrine neoplasia in England 1995–2018: A retrospective, population-based study

“…A comprehensive Swedish autopsy study comparing post-mortem to real-time diagnosis over a time period showed a high number of undiagnosed NEN in the small bowel. 18 A Canadian study showed that, despite overall increased NEN incidence, the proportion of those presenting with metastatic disease had decreased significantly, with earlier stage at diagnosis, and posited increased detection as the cause. 8 …”

“… 19 Diagnosing NEN at an earlier stage improves prognosis, and may be important in screening for other solid organ cancers. 18 …”

Relevant prognostic factors in patients with stage IV small intestine neuroendocrine neoplasms

“…Small intestinal neuroendocrine neoplasms (SI-NEN) are the most common small bowel tumours with an annual incidence of about 0.5-1.05/100.000/year in Western countries. [1][2][3] The primary tumours are often small, but they spread early to lymph nodes and the liver. 4 About 60% of patients have distant metastases at the time of diagnosis, mostly in the liver.…”

Time trends in incidence and survival of small intestinal cancer in Sweden

“…This hypothesis is particularly valid for NETs, which are often described as potentially indolent tumours. Studies from Malmö County during 1958–1982, with an autopsy frequency reaching 87 per cent of all deceased persons found an extremely high incidence of 53 small intestinal NETs per million person-years 14 , 15 . The vast majority of these patients had been asymptomatic.…”