Inherited syndromes involving pancreatic neuroendocrine tumors

Abstract

Inherited syndromes are important to recognize in the setting of a pancreatic neuroendocrine tumor (PNET) as there are significant implications for the patient's medical management and opportunity for early detection of subsequent manifestations. Although most PNETs are sporadic, approximately 10% are due to an inherited syndrome, which include multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 4 (MEN4), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). The general hallmarks of a hereditary endocrine neoplasia predisposition syndrome include any one of the following: multiple primary tumors (in the same or different organs), rare tumors (prevalence of less than 1 in 1,000 people in the general population), earlier age of diagnosis (usually under the age of 40), characteristic pattern of disease in the individual or family (phenotype and inheritance pattern). These syndromes are monogenic (due to a single gene disorder), highly penetrant (with all carriers of the disease exhibiting at least part of the phenotype) and can display variable expressivity (where affected individuals may have different presentations and features of the disease). A thoughtful approach to management is required, even if the presenting symptom is resolved, as these syndromes often involve multi-organ disease with a lifelong risk for tumor development. Additionally, the natural history of tumors in the setting of a hereditary condition may be different than would be expected in a sporadic form of the disease. For example, in some circumstances the risk of metastatic disease is lower, and therefor longer observation is the preferred approach over early surgical intervention. The unique aspects to management, challenges in hereditary disease recognition and accurate diagnosis, and rarity of these syndromes are all reasons to support referral to high-volume centers with the experience and knowledge to treat patients with hereditary endocrine neoplasia syndromes.

Keywords: Multiple endocrine neoplasia type 1 (MEN1); genetic counseling; neuroendocrine tumor; pancreatic neoplasms; von Hippel-Lindau disease (VHL).

Figure 1

MEN1 genetic testing criteria. MEN1, multiple endocrine neoplasia type 1.

Figure 2

Areas of the body affected by von Hippel-Lindau disease. For the National Cancer Institute © (2020) Terese Winslow LLC, U.S. Govt. has certain rights.

Figure 3

VHL diagnostic criteria. VHL, von Hippel-Lindau disease.