In mammals, virtually all of the PP-producing cells are located in the pancreas. They have been found within the islets, scattered in the exocrine compartment, and lining the ducts. Within the islets the PP cells are located mainly in the periphery, wedged between the A and B cells. PP islet cells are relatively abundant in both the murine ventral and dorsal pancreatic buds by day 15.5 of gestation. Subsequently, at day 18.5 of gestation, the total number of PP cells in the murine ventral bud has doubled, whereas the number in the murine dorsal bud has essentially remained unchanged [2
]. This nonhomogenous distribution of PP cells can also be seen in the human neonate. Indeed, PP cells are more numerous in the uncinate process than in the body and tail and rest of the pancreatic head. This anatomic distribution of PP cells is also present in the adult human pancreas [3
]. Infusions of PP in man demonstrate that, at physiological levels, it acts solely on the pancreas and gallbladder by inhibiting the secretion of bile and of pancreatic enzymes and juice [4
]. Thus a tumor deriving from PP cells is predicted to be clinically silent. That is this not always the case as illustrated in this case and table . In 1979, there was still controversy about how often WDHA syndrome, with a causal pancreatic tumor, is mediated by excessive secretion of VIP [4
]. Although elevated VIP serum levels were measured in the majority of patients, there have been reports about so-called Pseudo-Verner-Morrison syndromes with a clinical WDHA syndrome in the presence of normal VIP serum levels.
Pure PPomas with WDHA syndrome
Larsson et al. were the first to report on a patient with diarrhea due to a pancreatic tumor in whom PP was markedly elevated in the plasma with normal levels of VIP in the plasma [5
]. In 1980 Hayes presented a case of a PP-producing islet cell tumor causing WDHA [6
]. Unfortunately there are no more data like VIP serum levels of this case available. Four years later, Strodel et al. published a series of eight patients with PP-producing islet cell tumors [7
]. Two patients presented with diarrhea, but in only one of them a pancreatic tumor was found and resected. The last report came from Mortenson and Bold [8
]. They described a 64-year-old woman who presented with watery diarrhea in the presence of MEN-1 syndrome. Of various potential pancreatic endocrine hormones, only serum levels of PP were elevated. Radiologic imaging failed to identify a pancreatic tumor; her diarrhea was therefore managed with subcutaneous administration of somatostatin. Three years later she developed gallstone pancreatitis with the subsequent development of a pancreatic pseudocyst. At exploration for drainage of the pseudocyst, intraoperative ultrasound identified a 6-mm tumor in the distal pancreas that was resected. Final pathology documented a pancreatic endocrine tumor with immunohistochemical staining demonstrating the presence of PP. Beside these four cases, there have been multiple case reports about PPomas, excluded from table because either of lacking WDHA syndrome or because no real circumscribed pancreatic tumor could be identified [9
As shown in table , the normal serum level of VIP and the elevated serum level of PP suggest that the symptoms in our patient seem to be derived from the high levels of circulating PP. A correlation between the serum PP concentrations and the WDHA syndrome could be demonstrated by absence of the syndrome after removal of the tumor due to an immediate fall in serum PP. PPomas should be treated as nonfunctioning ETPs. Preoperatively US, CT scan or endoscopic ultrasound are the procedures of choice and are usually effective, because these tumors are relatively large [11
]. Also SRS can be performed to differentiate endocrine from nonendocrine pancreatic tumors. Recognition of ETPs is imperative because of their good resectability and excellent long-term survival compared to that of ductal pancreatic carcinoma [13
]. The major goal is a potentially curative resection with no tumor tissue left behind. This may require partial pancreatoduodenectomy in large tumors with local signs of malignancy or enucleation like in the present case.
Some years ago, Jensen described eight different neoplastic disorders that can cause chronic diarrhea [15
]. This list included gastrinomas, VIPomas, glucagonomas, somatostatinomas, and calcitonin-producing tumors. The present case suggests that, although rare, PPomas have to be added to this list.