Multiple endocrine neoplasia type 1 (MEN-1 syndrome) or Wermer’s syndrome is part of a group of disorders that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas. Although usually inherited as an autosomal dominant disorder, MEN1 can also occur sporadically (without a family history) as a result of new mutations. Up to 90% of all identified mutations predict a loss-of-function of menin, a protein involved in cell proliferation coded by a tumor suppressor gene located in chromosome 11. MEN1 follows the “two-hits” mutation model. The first hit is the heterozygous MEN1 germline (familial) mutation, or developed in an early embryonic stage (sporadic) and present in all cells at birth. The second hit is a MEN1 somatic mutation that occurs in the predisposed endocrine cell, and gives cells the survival advantage needed for tumor development. MEN1 syndrome is highly penetrant. Fifty percent of patients develop signs and symptoms by 20 years of age and more than 95% have symptoms by 40 years of age. Tumors associated with MEN1 present the characteristic adenoma-carcinoma sequence.

The commonest neoplasms are:

• Parathyroid hyperplasia and adenoma >90%
• Pancreatic endocrine neoplasms = 80%
• Pituitary neoplasms = 25-50%
• Other neoplasms = 5-30%

Pancreatic neuroendocrine neoplasms in MEN1 may be synchronous or metachronous with other MEN1-associated neoplasms. Pancreatic neoplasms are typically gastrinomas, insulinomas or other non-functional neoplasms. Tumors are very often multifocal, and tend to recur. These aspects are important to plan the best surgical strategy. Surgical resection at the time of diagnosis is necessary in insulinomas and when a hormonal syndrome is present, while the therapy of small gastrinomas or non-funcional neoplasms (<2 cm) is controversial. 

As discussed in the section on sporadic neoplasms, small incidentally discovered non-functional pancreatic neuroendocrine neoplasms are increasingly been diagnosed thanks to the widespread application of cross-sectional imaging, such as CT-scan and magnetic resonance imaging. Recent evidence suggests that small pancreatic lesions do not tend to metastasize, and that the development of metastases does not critically affect long-term survival. Accordingly, a non-operative approach (clinical and radiologic surveillance) is indicated for lesions < 2cm, while surgical resection should be undertakes when the tumor grows during the follow-up, or when metastases develop. In particular, surveillance of small MEN1-associated gastrinoma is safe, and the hormonal syndrome (Zollinger-Ellison) is well controlled by medical therapy. Surgical resection is recommended only for gastrinomas > 2cm.

The best surgical approach for MEN1-associated pancreatic neuroendocrine neoplasms is not well-established, and the choice of a parenchyma-sparing or a formal resection should be tailored to the single patient. Total pancreatectomy should be performed in patients with mutifocal lesions and a family history of aggressive disease. Formal resections (pancreaticoduodenectomy and left pancreatectomy) are indicated in large neoplasms, in neoplasms with lymph node involvement, and in multifocal lesions centered in the pancreatic head or body-tail. Intraoperative ultrasound is mandatory to rule out undetected lesions in the pancreatic remnant. Enucleation is mostly performed in insulinomas.