Carcinoid of the Minor Papilla in Incomplete Pancreas Divisum Presenting as Acute Relapsing Pancreatitis

Abstract

Carcinoid tumors arise from enterochromaffin cells and are usually found in the appendix, ileum, stomach, and rectum. Ampullary carcinoids are rare tumors. They most commonly present with obstructive symptoms like jaundice and nonspecific abdominal discomfort. They are difficult to diagnose preoperatively secondary to their relatively small size and submucosal location. We report the unusual case of carcinoid of the minor papilla in a patient with incomplete pancreas divisum presenting as acute relapsing pancreatitis. CASE REPORT A 35-year-old woman was referred to our hospital for evaluation of acute relapsing pancreatitis. She had developed right upper quadrant abdominal discomfort and intermittent nausea 8 months prior to referral. Three episodes of acute pancreatitis had been documented during this period with the peak amylase and lipase of 3142 (normal, 30–110 U/L) and 22,102 (normal, 23–300 U/L), respectively. She did not report any risk factors for pancreatitis such as alcohol or medication use, hypertriglyceridemia, or a positive family history. She was admitted to our hospital with a similar episode. Laboratory findings included a lipase of 915 U/L, amylase of 256 U/L, total bilirubin of 0.7 mg/dL, AST of 27 U/L, ALT of 21 U/L, and alkaline phosphate of 61 U/L. White blood count and hematocrit levels were within normal range. Ultrasound of the abdomen demonstrated a normal appearance of the gallbladder; the intra- and extra-hepatic biliary ducts were not dilated. CT scan showed no evidence of peripancreatic fluid collection, pancreatic mass, or calcification. At ERCP, a nodule with central ulceration was identified proximal to the ampulla of Vater. The cholangiogram was normal, but the pancreatogram was unsuccessful. Biliary manometry was normal. Bile analysis was positive for crystals; hence biliary sphincterotomy was performed. Biopsy of the nodule seen in the area of the minor papilla revealed small intestinal mucosa and submucosa with chronic inflammation. The patient's symptoms persisted, and, on a repeat ERCP done 2 months later, incomplete pancreas divisum was identified with filling of the dorsal duct through a very small branch of the ventral system (Figure 1). Clubbing of the side branches was seen, consistent with early chronic pancreatitis. The dorsal duct communicated with the area of the nodule at the minor papilla. The minor papilla could not be cannulated due to the nodule. Biopsy of the nodule again revealed small intestinal mucosa and submucosa with chronic inflammation.FIGURE 1.: ERCP findings. Incomplete pancreas divisum dorsal duct (A) filling with contrast through a very small branch (B) of the ventral duct (C).The patient was referred for a minor papilla sphincteroplasty. The nodule was resected during surgery, and the histology results were consistent with carcinoid. The patient underwent a transduodenal minor papilla sphincteroplasty with excision of the duodenal carcinoid and ductoplasty of the dorsal duct. Subsequent histologic assessment of the resected segment revealed a single nodule 1 cm in maximum diameter present in the submucosal space, with intact overlying duodenal mucosa. The chromogranin and synaptophysin immunostains were strongly positive for a carcinoid tumor that exhibited moderate nuclear atypia (Figure 2). The resected margins were tumor-free. At 6 months of follow-up, the patient was doing well with no further episodes of pancreatitis.FIGURE 2.: A: Hematoxylin–eosin section of the nodule from minor papilla. The tumor is composed of nests of uniform cells. The nuclei show fine chromatin (salt-pepper chromatin). B: Chromogranin immunostain. The tumor cells are strongly positive for chromogranin (original magnification, ×200).DISCUSSION GI tract carcinoids are rare tumors and have varied clinical manifestations based on location. 1 Most ampullary carcinoids present with nonspecific abdominal discomfort and jaundice. Isolated pancreatitis in the absence of cholestasis is an unusual presentation. 1,2 Rarely, ulcerated duodenal carcinoids can present as a source of significant gastrointestinal bleeding. 3,4 In the majority of patients with acute pancreatitis, common precipitating factors like alcohol or gallstones can be easily identified. In the absence of common causes, less common causes need to be considered. As illustrated in our patient, the finding of an ulcerated nodule at the minor papilla led to the identification and subsequent resection of a carcinoid. It is postulated that increased resistance and ductal hypertension caused by the smaller caliber of the accessory duct and the minor papilla may induce pancreatitis in pancreas divisum. 5 Accessory ductal outflow obstruction caused by the carcinoid at the minor papilla probably resulted in acute relapsing pancreatitis in this case. There are no specific risk factors for carcinoid, but in general but a higher incidence of ampullary and periampullary carcinoids has been described in patients with von Recklinghausen disease. 6 Preoperative diagnosis is rarely made because these lesions tend to be small and usually submucosal in location. Hence, deep (“tunnel”) biopsy samples should be obtained in such cases. 2 A high index of suspicion must be maintained for such lesions in the appropriate setting such as the young patient without the common risk factors for pancreatitis. In contrast to the carcinoid tumors that arise from the midgut, foregut-derived ampullary carcinoids very rarely cause the carcinoid syndrome. 7,8 Overall, approximately 80% to 90% of all carcinoids secrete serotonin or its precursor 5-hydroxy tryptophan, and other tumors rarely do so. 9 Measurements of serotonin and its metabolites like urinary 5-hydroxy indole acetic acid (5-HIAA) have been described to be very helpful in the diagnosis and postresection follow-up of carcinoids. 2,9 In our patient, those levels were not obtained preoperatively as the patient did not have any signs, symptoms, or histologic evidence to suggest a diagnosis of carcinoid tumor. Surgical resection is the therapy of choice for these lesions. Surgery may range from local excision to pancreaticoduodenectomy. Close follow-up after surgical resection is indicated as some carcinoid tumors may metastasize. 2,7 CONCLUSIONS We present the first reported case of carcinoid of the minor papilla in a patient with incomplete pancreas divisum presenting as acute relapsing pancreatitis. This case also underscores the importance of evaluating patients with acute pancreatitis without identifiable risk factors for other less common etiologies like pancreatico-biliary structural abnormalities or mass lesions.