A VIPoma or vipoma () is a rare endocrine tumor that overproduces vasoactive intestinal peptide (thus VIP + -oma). The incidence is about 1 per 10,000,000 per year. VIPomas usually (about 90%) originate from the non-β islet cells of the pancreas. They are sometimes associated with multiple endocrine neoplasia type 1. Roughly 50–75% of VIPomas are malignant, but even when they are benign, they are problematic because they tend to cause a specific syndrome: the massive amounts of VIP cause a syndrome of profound and chronic watery diarrhea and resultant  dehydration, hypokalemia, achlorhydria, acidosis, flushing and hypotension (from vasodilation), hypercalcemia, and hyperglycemia. This syndrome is called Verner–Morrison syndrome (VMS), WDHA syndrome (from watery diarrhea–hypokalemia–achlorhydria), or pancreatic cholera syndrome (PCS). The eponym reflects the physicians who first described the syndrome. Symptoms and signs
The major clinical features are prolonged watery diarrhea (fasting stool volume > 750 to 1000 mL/day) and symptoms of hypokalemia and dehydration. Half of the patients have relatively constant diarrhea while the rest have alternating periods of severe and moderate diarrhea. One third have diarrhea < 1yr before diagnosis, but in 25%, diarrhea is present for 5 yr or more before diagnosis. Lethargy, muscle weakness, nausea, vomiting and crampy abdominal pain are frequent symptoms. Hypokalemia and impaired glucose tolerance occur in < 50% of patients. Achlorhydria is also a feature. During attacks of diarrhea, flushing similar to the carcinoid syndrome occur rarely.
These cases of HLH are classified as belonging to the class of Epstein–Barr_virus–associated_lymphoproliferative_diseases and termed EBV+ HLH. Genetics
Five genetic subtypes (FHL1, FHL2, FHL3, FHL4, and FHL5) are described, with an estimated overall prevalence of one in 50,000 and equal gender distribution. Molecular genetic testing for four of the causative genes, PRF1 (FHL2), UNC13D (FHL3), STX11 (FHL4), and STXBP2 (FHL5), is available on a clinical basis. Symptoms of FHL are usually evident within the first few months of life and may even develop in utero. However, symptomatic presentation throughout childhood and even into young adulthood has been observed in some cases.The five subtypes of FHL are each associated with a specific gene:

FHL1: HPLH1
FHL2: PRF1 (Perforin)
FHL3: UNC13D (Munc13-4)
FHL4: STX11  (Syntaxin 11)
FHL5: STXBP2 (Syntaxin binding protein 2)/UNC18-2Nearly half of the cases of type 2 familial hemophagocytic lymphohistiocytosis are due to bi-allelic PRF1 mutations. Pathophysiology
The underlying causes, either inherited or acquired, lead to an unchecked immune response when exposed to triggers. Impaired NK-cell cytotoxicity is the hallmark of HLH. All genetic defects for familial HLH are related to granule-dependent cytotoxicity. This inability to remove infected and antigen-presenting cells and terminate the immune response leads to uncontrolled proliferation and activation of the immune system with release of excessive cytokines. These cells then infiltrate organs, releasing more cytokines, which gives the clinical picture. The fever is caused by IL-1, IL-6 and TNF-alpha; the cytopenia is due to the suppressive effect on hematopoiesis by TNF-alpha and TNF-gamma. TNF-alpha and TNF-gamma may also lead to inhibition of lipoprotein lipase or stimulate triglyceride synthesis.