Clinical and Pathological Features of EC-cell Familial Small Intestine Neuroendocrine Tumors: A Nationwide Cohort From the French GTE-RENATEN Network.

Abstract

EC-cell familial small intestine neuroendocrine tumors (EC-cell F-SINET) are a recently described but poorly characterized entity. We aimed to describe their clinical and pathological features, and to compare them to patients with a sporadic form (EC-cell S-SINET). We constituted a nationwide cohort including (retrospectively patients diagnosed before 2012 and prospectively from 2012 to 2022) all patients with F-SINET (histologically proven SINET in ≥ 2 first or second-degree relatives) managed in the French GTE-RENATEN network. Clinical and pathological data were described and compared to the GTE-RENATEN population-based cohort including 2460 patients with EC-cell S-SINET using multivariable logistic regression. The survival impact of EC-cell F-SINET was explored using Cox proportional hazard analyses. We included 92 patients with EC-cell F-SINET from 47 families. Median age at diagnosis was 60.4 years. Among these patients, 22% had a history of another cancer, 76.1% had synchronous or metachronous metastases, 38% had a carcinoid tumor syndrome, and median Ki-67 labeling index was 2%. Median survival was 204.6 months. Multifocal EC-cell SINET were present in 66.7% of patients with EC-cell F-SINET and were associated with poorer prognosis (p = 0.005). In comparison with EC-cell S-SINET patients, those with EC-cell F-SINET had more frequent multifocal primary tumor in the small bowel (p < 0.0001) and carcinoid syndrome (p = 0.038), lower Ki-67 index and tended to be younger (p = 0.094). After adjustment on independent prognostic factors (age at diagnosis, metastatic stage, carcinoid tumor syndrome and Ki-67 index), EC-cell F-SINET did not have a different prognosis than that of EC-cell S-SINET. Patients with EC-cell F-SINET are characterized by more frequent multifocal EC-cell SINETs and more frequent carcinoid tumor syndrome, but their prognosis seems similar compared to patients with EC-cell S-SINET.