Multiple Endocrine Neoplasia Type 1

Abstract

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic disease of autosomal dominant inheritance, with an estimated prevalence of 3-20/100 000. Its main feature is neuroendocrine neoplasia in the parathyroid glands, the endocrine pancreas, the duodenum, and the pituitary gland. In this article, we review the diagnostic and therapeutic options for MEN1-associated tumors.

Methods: We present an analysis and evaluation of retrospective case studies retrieved from PubMed, guidelines from Germany and abroad, and our own experience.

Results: The disease is caused by mutations in the MEN1 gene. Mutation carriers should participate in a regular, specialized screening program from their twenties onward. The early diagnosis and individualized treatment of MEN1-associated tumors can prevent the development of life-threatening hormonal syndromes and prolong the expected life span of MEN1 patients from 55 to 70 years, as well as improving their quality of life. Surgical treatment is based on the location, size, growth dynamics, and functional activity of the tumors. The evidence for treatment strategies is derived from retrospective studies only (level III evidence) and the optimal treatment is often a matter of debate. This is a further reason for treatment in specialized centers.

Conclusion: MEN1 is a rare disease, and, consequently, the evidence base for its treatment is limited. Carriers of disease-causing mutations in the MEN1 gene should be cared for in specialized interdisciplinary centers, so that any appreciable tumor growth or hormonal activity can be detected early and organ-sparing treatment can be provided.

eFigure:

Organ-sparing surgical treatment of MEN1 patient with multiple pNENs A young female patient (in her twenties) presented with abdominal complaints. Initial imaging revealed two masses, one located in the head and one in the tail of the pancreas (marked with → in B1, B2 and C1). Further diagnostic testing confirmed organic hyperinsulinism. Moreover, the young patient had been diagnosed with a macroprolactinoma two years earlier. Genetic testing confirmed the diagnosis of MEN1. Endoscopic ultrasound revealed multiple (> 5) pNENs <1 cm in addition to the two known masses (A1, pancreatic head mass with a tumor diameter of 25.7 mm; A2, pancreatic tail mass with a tumor diameter of 38.8 mm). A supplementary MRI examination was also obtained (B1, pancreatic head mass; B2, pancreatic tail mass) as well as a ⁶⁸Ga-DOTATOC PET/CT (C1, pancreatic head mass; C2, pancreatic tail mass). The mass in the pancreatic tail (C2) showed no tracer enhancement (*) in the ⁶⁸Ga-DOTATOC PET/CT scan. The two masses, measuring >2 cm in diameter, in the head and tail of the pancreas were only treated with an organ-sparing pancreatic tail resection and an enucleation of the pancreatic head lesion, while the remaining NF-pNENs <1 cm were left in place. Image series D shows the surgical specimens (D1, enucleation pNEN from the pancreatic head; D2, organ-sparing pancreatic tail resection of an insulinoma). Histopathology confirmed that the pancreatic head lesion was a well- differentiated neuroendocrine tumor (G1) and the pancreatic tail lesion an insulinoma G1 pT2 pN1 (2/16) L0 V0 Pn0 R0. In the peripancreatic adipose tissue that was also removed during the organ-sparing pancreatic tail resection, two microscopically small lymph node metastases were identified. (Photos A1 and A2: Prof. Denzer, Philipps University, Marburg, Germany)