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A Veltroni, E Cosaro, F Spada, N Fazio, A Faggiano, A Colao, S Pusceddu, M C Zatelli, D Campana, A Piovesan, A Pia, E M Grossrubatscher, A Filice, A Bianchi, P Razzore, M Toaiari, S Cingarlini, L Landoni, R Micciolo and M V Davì

Introduction

Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series.

Aim of the study

To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma.

Materials and methods

Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017.

Results

The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients.

Conclusions

Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.