Shades of insulinoma one century after first extensive evaluation by Wilder and colleagues; a figurative review between light and dark.

In the fall of 1926, a 40-year-old physician was admitted to Mayo Clinic with worsening bouts bouts of faintness and paraesthesias associated with missed meals and physical exertion and which could be prevented by food or sweet drinks. Given that the symptoms were similar to an insulin overdose, the patient wanted his "spontaneous hyperinsulinism" evaluated. The dedicated team of R.M. Wilder, F.N. Allan, M.H. Power and H.E. Robertson investigated of Langerhans. Upon surgical exploration by Dr. W.J.Mayo, the body and tail of the pancreas were found to have multiple tumors, and there were liver metastases. The disease was unresectable, and the patient died one month after surgery. Pathology revealed the tumor cells to be consistent with carcinoma of the Islets of Langerhans. Extracts dervied from the liver metastases lowered blood glucose in rabbits, proving the metastases were from the insulin-producing carcinoma. Thus, Wilders, et al. published the first report of an insulinoma in 1927. One century later, insulinomas remain fascinating and challenging. In commemoration of one century of insulinoma-related clinical and basic research, this narrative review describes key breakthroughs and presents, by means of seven case studies, the clinical spectrum of insulinomas and their clinical courses, from benign to fatally malignant.