Pancreatic neuroendocrine tumors in patients with tuberous sclerosis: A multicenter study and systematic review
Kalyan Mansukhbhai Shekhda, John Howat, Yujia Gao, Anat Bel-Ange, Simona Grozinsky-Glasberg, Gregory Kaltsas, Kai Man Alexander Ho, Aimee R Hayes, Dalvinder Mandair, Christos Toumpanakis, Efthimia Karra, Richard A Dixon, Deirdre Donnelly, Elizabeth A Jones, Colin H Jones, Finbar O’Callaghan, Asheesh Sharma, Kirsten Slaney, Aviva Frydman, Rajaventhan Srirajaskanthan, Nabil Kibrya, Martyn Caplin, Frances Elmslie, Ashley GrossmanAbstract
Introduction
Pancreatic neuroendocrine tumors (pNETs) are a recognized feature of tuberous sclerosis complex (TSC). The current evidence suggests that pNETs occurring in TSC may exhibit a different clinical course from sporadic cases, but their natural history remains poorly characterized.
Objective
This study aimed to characterize the demographics, clinical presentation, management and long-term outcomes of TSC-associated-pNETs), and to propose possible guidelines for surveillance and management.
Materials and Methods
We conducted a multicenter retrospective review of TSC-pNET patients from 6 UK TSC Specialist Clinics and from three NET referral centers, from 2008 to 2024. Data on demographics, tumor characteristics, management and outcomes, were collected. A systematic review of the literature from 2009 to 2026 on TSC-pNETs was also performed.
Results
We identified a total of 26 consecutive cases with the TSC-pNET-association in our cohort (21 cases of pNETs from TSC Specialist Clinics (1.1% of the population), and 5 cases of TSC-pNETs from the NET referral centers (0.25% of the population). An additional 80 cases were identified from the published literature. We observed a wide spectrum of clinical phenotypes, with the majority being non-functioning pNETs (n:24, 92%), whereas two patients were diagnosed with glucagonomas. Surgical intervention was the mainstay initial treatment, the indication being either functional pNETs, or large or symptomatic non-functioning pNETs.
Conclusions
TSC-pNETs are rare and mostly non-functioning tumors with variable clinical behavior. Due to their uncertain malignant potential, we suggest that baseline pancreatic imaging should be incorporated into TSC surveillance, and emphasize the need for heightened pNETs surveillance and updated management recommendations.