Clinical characteristics of gastrointestinal stromal tumors with hypoglycemia

The development of tyrosine‑kinase inhibitors has improved survival rates for patients with gastrointestinal stromal tumors (GISTs). Despite the progress, not all the patients can universally receive the benefit from treatment due to the individual underlying conditions in a real‑world setting. The present study focused on the well‑known but under‑studied condition of GIST with hypoglycemia. Hypoglycemia in GIST is characterized by hypoglycemic symptoms such as dizziness, sweating and confusion. It is caused by several factors such as multiple liver metastases, drug adverse effects, postoperative complications and paraneoplastic syndrome [non‑islet cell tumor hypoglycemia (NICTH)]. Comprehensive analysis of this condition has been hindered due to its rarity, and has been mostly limited to case reports. In the present study, a single‑institution retrospective analysis of GIST with hypoglycemia was conducted to investigate its prevalence and prognosis, and the cause of this condition. The present study identified that the prevalence of hypoglycemic episodes of GIST was 4.1% in all patients with GIST, and recurrent hypoglycemic cases had a poor prognosis. The present study identified 1 case with recurrent hypoglycemia due to NICTH. Since NICTH is a rare hypoglycemic cause and requires further evaluation, an autopsy and genetic sequencing were performed using the available clinical materials. Through this histological and genetic investigation, the histological diversity of NICTH‑GIST was revealed and insulin‑like growth factor II (IGF‑II) amplification was identified. Furthermore, a chronological analysis was performed using multiple resected archived samples from the same case, and revealed that diffuse IGF‑II expression may have occurred in the early phase of tumor development. The present study catalogued the characteristics of GIST with hypoglycemia with a focus on NICTH‑GIST.