Opinion Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 6, 2022; 10(16): 5124-5132
Published online Jun 6, 2022. doi: 10.12998/wjcc.v10.i16.5124
Malignant insulinoma: Can we predict the long-term outcomes?
Maja Cigrovski Berkovic, Monika Ulamec, Sonja Marinovic, Ivan Balen, Anna Mrzljak
Maja Cigrovski Berkovic, Department of Endocrinology, Diabetes, Metabolism and Clinical Pharmacology, Clinical Hospital Dubrava, Zagreb 10000, Croatia
Maja Cigrovski Berkovic, Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
Monika Ulamec, Department of Pathology and Cytology “Ljudevit Jurak”, University Hospital Center “Sestre milosrdnice”, Zagreb 10000, Croatia
Monika Ulamec, Scientific Group for Research on Epigenetic Biomarkers and Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Sonja Marinovic, Laboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb 10000, Croatia
Ivan Balen, Department of Gastroenterology and Endocrinology, General Hospital “Dr. Josip Bencevic”, Slavonski Brod 35000, Croatia
Anna Mrzljak, Department of Gastroenterology and Hepatology, UHC Zagreb, Zagreb 10000, Croatia
Anna Mrzljak, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Author contributions: Cigrovski Berkovic M made contribution to the conception and design of the study, and drafted and revised the manuscript critically; Marinovic S, Ulamec M, Balen I, and Mrzljak A collected the data, and drafted and wrote the manuscript; all authors read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maja Cigrovski Berkovic, MD, PhD, Associate Professor, Department of Endocrinology, Diabetes, Metabolism and Clinical Pharmacology, Clinical Hospital Dubrava, Avenija Gojka Suska 6, Zagreb 10000, Croatia. maja.cigrovskiberkovic@gmail.com
Received: November 13, 2021
Peer-review started: November 13, 2021
First decision: January 9, 2022
Revised: January 17, 2022
Accepted: April 21, 2022
Article in press: April 21, 2022
Published online: June 6, 2022
Processing time: 200 Days and 12.6 Hours
Core Tip

Core Tip: Insulinomas are rare but potentially malignant tumors. The only sure sign of malignancy is metastases present at diagnosis. Long-term survival of patients with malignant insulinoma is poor; however, newly available agents and approaches, are reassuring. Nonetheless, it is important to distinguish between benign and malignant insulinomas early, as well as follow the non-functioning pancreatic neuroendocrine tumors and plan the appropriate treatment and follow-up. Important initial parameters include 2-3-fold higher insulin, proinsulin, and C-peptide levels, early-onset hypoglycemia during the 72-h fasting test, and high chromogranin A from the biochemical aspect, earlier recognition of neuroglycopenic symptoms from the clinical aspect, and tumor size exceeding 3 cm and higher tumor grade (G2 or G3) from the pathohistological standpoint. Molecular genetic advances are still insufficient in adding to the individualization of treatment and prognosis, but α-internexin and chromosomal instability, where available, might add to early recognition of malignancy.