Unique Metastatic Patterns in Neuroendocrine Neoplasms of Different Primary Origin

Introduction Neuroendocrine neoplasms (NEN) can originate in different organs, e.g. the gastroenteral tract (GE), pancreas (Pan) or lung (L). Our aim was to examine metastatic patterns for patients with NEN of various primary origins with a special focus on brain metastases to indicate utility for screening. Methods All NEN patients except for small cell lung cancer registered in the Netherlands Cancer Registry from 2008-2018 were selected. Metastatic patterns at initial diagnosis for NEN with different primary origin were compared. In a subcohort of patients from two referral hospitals (2014-2019), additional information on for example development of metastases after initial presentation was available. Results In the nationwide cohort 4,768/11,120 (43%) patients had metastatic disease at diagnosis (GE 1,504/4,710 (32%), Pan 489/1,150 (43%), L 1,230/2,978 (41%)). For GE- and Pan-NEN, the most prevalent metastatic site was the liver (25% and 39%), followed by distant lymph nodes (8% and 8%), whereas only few patients with brain metastases were identified (0% in both). In contrast, for L-NEN, prevalence of metastases in liver (19%), brain (9%), lung (7%) and bone (14%) was more equal. In the reference network cohort, slightly more NEN patients had metastatic disease (260/539, 48%) and similar metastatic patterns were observed. Conclusion Almost half of NEN patients were diagnosed with synchronous metastatic disease. L-NEN have a unique metastatic pattern compared to GE- and Pan-NEN. Remarkably, an important part of L-NEN metastases were in the brain, whereas brain metastases were almost absent in GE- and Pan-NEN, indicating utility of screening in L-NEN.