The current strategy for managing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an inherited autosomal dominant disease presenting with pancreatic neuroendocrine tumors (pNETs), parathyroid tumors, or pituitary tumors. Using the PubMed database, we reviewed the literature on information regarding the proper diagnosis and treatment of MEN1-associated pNET. Many cases of MEN1-associated pNET are functioning pNETs. Gastrinomas and insulinomas tend to occur frequently in the duodenum and pancreas, respectively. In addition to diagnostic imaging, the selective arterial secretagogue injection test (SASI test) is useful for localizing functioning pNET. The standard treatment is surgical resection. However, in the case of a functioning pNET, the tumor should first be accurately located using the SASI test before an appropriate surgical method is selected. In cases of a MEN1-associated non-functioning pNET that exceeds 2 cm in diameter, the incidence of distant metastasis is significantly increased, and surgery is recommended. In cases of unresectable pNET, a somatostatin analog has been shown to demonstrate antitumor effects and is considered to be a promising treatment. In addition, molecular-targeted drugs have recently been found to be effective in phase III clinical trials.

Keywords: Multiple endocrine neoplasia type 1; Multiple tumors; Pancreatic neuroendocrine tumor; Selective arterial secretagogue injection test.

Fig. 1

A case of MEN1-unassociated insulinoma (34-year-old female). (A) Abdominal imaging computed tomography (CT). A tumor with a slight early phase stain pattern is observed at the pancreatic head and body border (arrow). (B) Endoscopic ultrasonography. A tumor is observed at the site shown using CT (arrowheads). No other tumors are detected in the pancreas.

Fig. 2

A case of MEN1-associated insulinoma (44-year-old male). (A) Abdominal imaging computed tomography (CT). A tumor with an early phase stain pattern is observed at the pancreatic head and body border (arrow). (B) Endoscopic ultrasonography. In addition to the lesion shown using CT, small tumors are found at the pancreatic head, body, and tail. The case is considered to have multiple pancreatic lesions. The arrowhead shows a 3-mm lesion in the pancreatic body.

Fig. 3

The selective arterial secretagogue injection test data from the case in Fig. 1. (A) Gastroduodenal artery. (B) Splenic artery. (C) Superior mesenteric artery, and (D) dorsal pancreatic artery. Step-up is found only in (D). IRI, immunoreactive insulin; CPR, C-peptide immunoreactivity.

Fig. 4

The selective arterial secretagogue injection test data from the case in Fig. 2. (A) Gastroduodenal artery. (B) Splenic artery. (C) Superior mesenteric artery, and (D) dorsal pancreatic artery. Step-up is found in (A), (B), and (D). In this case, a parathyroid tumor is found in addition to the pancreatic endocrine tumor. IRI, immunoreactive insulin; CPR, C-peptide immunoreactivity.