Clinico–pathological features, treatments and survival of malignant insulinomas: a multicenter study

Abstract

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.

Carcinoid Syndrome and Hyperinsulinemic Hypoglycemia Associated with Neuroendocrine Neoplasms: A Critical Review on Clinical and Pharmacological Management

“…However, HH can occasionally present during the follow-up of patients with originally metastatic NF-PanNEN, with a negative impact on the prognosis [54]. Malignant INSs, that exhibit local invasion and/or distal metastases, as a biological feature that differentiates malignant cases from benign ones [55], account for 10% of all cases of INSs [56]. Some pathological criteria could also be suggestive of malignancy, including lesions >2 cm, grading >G2 according to WHO 2019, or the presence of vascular invasion, perineural invasion or necrosis [57,58].…”

“…Some pathological criteria could also be suggestive of malignancy, including lesions >2 cm, grading >G2 according to WHO 2019, or the presence of vascular invasion, perineural invasion or necrosis [57,58]. They are usually characterized by severe HH that is refractory to symptomatic treatment [56] and unlike benign INSs can cause prominent neuroglycopenic symptoms.…”

Editorial—Special Issue: Foreword to the Special Issue on NIKE: Neuroendocrine Tumors, Innovation in Knowledge and Education

“…On the other hand, pathologists are indispensable to achieve the diagnosis and define the histo-prognostic category (5). Despite recent advances in the comprehension of biology and clinical behavior of these tumors, as well as the development of new diagnostic tools and therapeutic agents, many unmet needs remain to be addressed (6)(7)(8). Furthermore, quality of life and management of treatment toxicities represent a challenge in these patients who are characterized by long survival even at a metastatic stage (9)(10)(11)(12).…”

Caratteristiche clinico-patologiche, gestione clinica e prognosi dell’insulinoma maligno: studio multicentrico italiano

“…Tabella 1 Caratteristiche clinico-patologiche, dati di laboratorio e di diagnostica per immagini dei pazienti affetti da insulinoma maligno [7] Caratteristiche cliniche e anatomo-patologiche (N = 31 pazienti)…”

“…Un recente studio retrospettivo multicentrico italiano [7], condotto in 13 centri di riferimento, ha analizzato 31 pazienti affetti da insulinoma maligno seguiti nel periodo 1988-2017 (Tabella 1). Lo studio ha analizzato le caratteristiche clinico-patologiche, le modalità di trattamento e i principali fattori prognostici che influiscono l'outcome, alla ricerca di una strategia terapeutica mirata, basata su evidenze cliniche.…”