Incidence, Clinical Presentation and Trends in Indication for Diagnostic Work-Up of Small Intestinal and Pancreatic Neuroendocrine Tumors

Abstract

Background: The incidence of small intestinal (SI) and pancreatic neuroendocrine tumors (siNETs and pNETs) seems to have increased. The increased frequency of incidental findings might be a possible explanation. The study aimed to examine (1) changes in incidence and the stage at diagnosis (2010-2011 vs. 2019-2020), (2) changes in the initial indication for diagnostic workup and 3) the differences in stage between incidentally discovered vs. symptomatic disease during the entire study period.

Methods: We performed a retrospective study, that includes consecutive siNET and pNET patients referred to the Copenhagen ENETS center of excellence in 2010-2011 and 2019-2020.

Results: The annual incidence of siNET per 100,000 increased from 1.39 to 1.84, (p = 0.05). There was no change in the stage at diagnosis, and in both periods approximately 30% of patients were incidentally diagnosed (p = 0.62). Dissemination was found in 72/121 (60%) of symptomatic vs. 22/50 (44%) of incidentally discovered SI tumors in the entire cohort, (p = 0.06). The annual incidence of pNET increased from 0.42 to 1.39 per 100,000, (p < 0.001). The proportion of patients with disseminated disease decreased from 8/21 (38%) to 12/75 (16%), (p = 0.02) and the number of incidental findings increased from 4/21 (19%) to 43/75 (57%), (p = 0.002). More symptomatic patients had disseminated disease compared to patients with incidentally discovered tumors (15/49 (31%) vs. 5/47 (11%), (p = 0.01)).

Conclusion: The incidence of siNET and pNETs increased over the past decade. For siNETs, the stage of disease and the distribution of symptomatic vs. incidentally discovered tumors were unchanged between the two periods. Patients with pNETs presented with more local and incidentally discovered tumors in the latter period. Patients with incidentally discovered siNETs had disseminated disease in 44% of the overall cases. The vast majority of incidentally found pNETs were localized.

Keywords: clinical presentation; incidence; incidentaloma; small intestinal and pancreatic neuroendocrine tumors.

Figure 1

Flowchart illustrating patient selection. Flowchart illustrating excluded patients and the number of small intestinal and pancreatic NETs included. Abbreviations: Neuroendocrine Tumor (NET). Small intestinal NET (siNET). Pancreatic NET (pNET) Gastroenteropancreatic NET (GEPNET).

Figure 2

Time trends in disease stage at referral. (A) Time trends in disease stage at referral of small intestinal NETs in the two calendar years 2010–2011 and 2019–2020. (B) Time trends in disease stage at referral of pancreatic NETs in the two calendar years 2010–2011 and 2019–2020. The p-value illustrates the difference between the calendar periods. Abbreviation: Neuroendocrine Tumor (NET).

Figure 3

Disease stage symptomatic vs. incidental findings in the entire cohort. (A) Disease stage of small intestinal NETs when comparing symptomatic vs. incidental findings in the entire cohort (2010, 2011, 2019 and 2020). (B) Disease stage of pancreatic NETs when comparing symptomatic vs. incidental findings in the entire cohort. The p-value illustrates the difference between the symptomatic and incidental findings. Abbreviation: Neuroendocrine Tumor (NET).

Figure 4

Imaging of a patient with incidentally discovered small intestinal NET. ⁶⁸Ga-DOTATOC-PET from a patient with disseminated incidentally discovered small intestinal NET in a seventy-five-year-old man. As part of the investigation for prostate cancer, an MRI of the prostate was performed, and a tumor in the abdomen was incidentally discovered. In retrospect he reported loose stools for a year. He did not have flushing or other general symptoms of malignant disease. The patient had a primary tumor of 2.9 cm placed in right lower quadrant (illustrated by the arrow), a 5.5 cm mesentery metastasis and multiple lymph node metastasis. Moreover, the patient presented with metastasis in the sternum, left scapula, left ileal bone and in mediastinal lymph nodes. The picture has been published with the patient’s permission.