Syndromic versus non-syndromic sporadic gastrin-producing neuroendocrine tumors of the duodenum: comparison of pathological features and biological behavior

Abstract

Sporadic gastrin-producing neuroendocrine tumors of the duodenum present either with the Zollinger-Ellison syndrome (ZES) or with unspecific symptoms. While syndromic gastrin-producing neuroendocrine tumors often show metastases at the time of diagnosis, those without a syndrome do not. The aim of the study was to search for clinicopathological features that may distinguish the two categories of gastrin-producing duodenal tumors. In a retrospective study, we analyzed the clinical and pathological data in a series of 41 patients with syndromic (i.e., gastrinomas) or non-syndromic duodenal gastrin-producing neuroendocrine tumors (ns-gas-NETs). Twenty-four (59 %) of the 41 patients had tumors that were associated with a ZES and were classified as gastrinomas. These tumors showed a higher Ki-67 index than that of the ns-gas-NETs (1.74 vs. 0.85 %, p = 0.012). In addition, they had more lymph node metastases (75 vs. 6 %, p < 0.001) and showed liver metastases and thus presented much more frequently in TNM stage ≥III (75 vs. 6 %; p < 0.001) than their non-syndromic counterparts. Gastrinomas were removed surgically, ns-gas-NETs endoscopically. We did not observe any significant differences in overall survival or recurrence of disease. Duodenal gastrinomas show no clear morphological features that distinguish them from their non-syndromic counterparts. However, the patients with gastrinomas present in a more advanced stage of disease and need surgical treatment, while non-syndromic gastrin-producing duodenal NETs may be cured by complete endoscopical removal.

Four Neuroendocrine Tumor Types and Neuroendocrine Carcinoma of the Duodenum: Analysis of 203 Cases

“…In accordance with an investigation by Rosentraeger et al [18] (published online after this study was completed), no histological/histochemical difference was found between gastrin-expressing neoplasms with or without associated endocrine hyperfunction syndrome, nor did tumor mass account for their different functional behavior. Indeed, active gastrinomas, especially those multicentrically arising in a background of MEN1, were among the smallest duodenal NETs [4], [5].…”

S2k-Leitlinie Neuroendokrine Tumore

“…Rosentraeger et al [305] beobachteten bei einem Vergleich von 41 Patienten, dass bei Tumoren ohne Zeichen hormoneller Symptome seltener Metastasen nachgewiesen werden als bei Tumoren mit hormonellen Syndromen (6 vs. 75 %).…”

Gastrin Induces Nuclear Export and Proteasome Degradation of Menin in Enteric Glial Cells

“…Approximately 25–33% of MEN1 patients develop gastrinomas, which are small, multi-focal lesions present in Brunner’s glands 5 , tubular structures that secrete mucus, growth factors and bicarbonate located within the submucosa of the proximal duodenum 7 . Therefore, MEN1 -based gastrinomas do not appear to develop from the intestinal epithelium but instead arise from glands located in the submucosa 8, 9 . Less than 50% of MEN1 gastrinomas develop loss of heterozygosity (LOH) suggesting that other mechanisms contribute to loss of WT menin protein function 8, 10, 11 .…”