Giant insulinoma: report of a case and review of published reports

Abstract

BackgroundLarger insulinomas are reportedly more likely to be malignant; however, their biological behavior has not been clearly elucidated. We here report the characteristics and treatment of a giant insulinoma with local invasion and lymph node metastasis. We also review published reports concerning the clinical features of giant insulinomas and comparing their grading with that of pancreatic neuroendocrine tumors.Case presentationA 71-year-old man was referred to our hospital for investigation of persistent hypoglycemia. On the current presentation, laboratory tests showed serum glucose, immunoreactive insulin, and C peptide concentrations of 45 mg/dL, 17.2 μIU/mL and 4.1 ng/mL, respectively. Dynamic magnetic resonance imaging showed a hypervascular tumor measuring 13.5 cm in the head of the pancreas. Computed tomography scanning demonstrated local invasion and lymph node involvement. He thus had Whipple’s triad, which is associated with malignant insulinoma. No distant metastases having been identified, pancreaticoduodenectomy was performed. Intraoperatively, three separate tumors were identified in the pancreatic head. Pathological examination showed all three tumors were pancreatic neuroendocrine tumors; the tumor cells in the largest mass were strongly immunoreactive for insulin. The Ki-67 index was 2–5% in most parts of the largest tumor and over 20% in the poorly differentiated areas. This tumor was classified as neuroendocrine carcinoma in accordance with the 2010 World Health Organization classification of pancreatic endocrine neoplasms. He remains free of evidence of recurrence 2 years postsurgery.A review of published reports indicated that giant insulinomas are more malignant than smaller ones, and metastatic disease is found on presentation in 56% of patients with giant insulinomas; however, we were unable to identify any correlation between grade of pancreatic neuroendocrine tumor and biological behavior of giant insulinomas.ConclusionsGiant insulinomas more frequently exhibit malignant behavior, such as local invasion, lymph node involvement, and liver metastasis, than smaller ones. However, there was no relationship between grade and rate of metastases or survival in this small case series. Identification of useful biological markers is necessary.

Alternative Lengthening of Telomeres and Differential Expression of Endocrine Transcription Factors Distinguish Metastatic and Non-metastatic Insulinomas

“…Several studies have reported large insulinomas to be malignant more often, and the late symptomatology suggests relatively low or acquired insulin production (Fig. 2) [1,38,39]. The ARX transcription factor is not expected to be expressed in insulinomas [40], as it is not expressed in pancreatic beta-cells [41,42].…”

Nfe2l1-silenced insulinoma cells acquire aggressiveness and chemoresistance

“…Nfe2l1-deficient insulinoma cells show a marked chemotherapeutic resistance through the HK1-mPTPrelated metabolic pathway. The fact that Nfe2l1 deficiency in inoculated cells resulted in a more rapid tumor growth and aggressiveness potentially indicates an impact on tumor progression as recent evidence indicates that larger insulinomas are more frequently malignant than smaller ones (Ueda et al 2016). This study provides additional evidence that NFE2L1 is involved in chemotherapeutic resistance and indicates NFE2L1 modulation could be an important therapeutic target in the future to help prevent or cure certain cancers.…”

“…In vitro, the Nfe2l1-KD MIN6 cells were also hyperproliferative, showed enhanced migration/ invasiveness and displayed chemotherapeutic resistance. In this regard, recent clinical evidence indicates that larger insulinomas more frequently show malignant characteristics, such as local invasion or metastasis to the liver, than smaller tumors (Ueda et al 2016). The drug resistance from Nfe2l1-KD deficiency appeared to be due to resistance to chemotherapeutic-induced mitochondrial damage and was due to upregulation of HK1, which was localized in mitochondria and caused mPTP closure.…”

Difficulties in Correction of Recurrent Hypoglycemia in a Patient With a Progressive Course of Malignant Metastatic Insulinoma

“…In a benign process, surgical treatment in most cases contributes to complete remission of the disease (relapse is no more than 3%); in the case of a malignant type of insulin-producing tumor in 2/3 of cases metastasis is not observed [3]. At the same time, in case of the metastatic liver lesion, the average survival rate of patients does not exceed several years [4]. The diagnosis of malignant insulinoma in our patient was obvious and established more than 10 years ago and the features of the clinical picture, which deserve the attention of internists and endocrinologists, first of all, were determined by difficulties in correcting of severe recurrent hypoglycemia against the background of a steady progression of the underlying disease despite the polychemotherapy (PCT) and sevenfold appliance of high-tech care, embolization and chemoembolization (CE) of the hepatic arteries.…”