|GENITOURINARY - CASE REPORT
|Year : 2011 | Volume
| Issue : 4 | Page : 496-499
Periampullary carcinoid: An uncommon tumor at an unusual site
A Somani, AK Jain, VK Dixit
Department of Gastroenterology, I.M.S., B.H.U. Varanasi, India
|Date of Web Publication||25-Jan-2012|
Department of Gastroenterology, I.M.S., B.H.U. Varanasi
Source of Support: None, Conflict of Interest: None
Gastrointestinal carcinoid tumors represent a group of well-differentiated tumors originating from various neuroendocrine cells located in the gastrointestinal mucosa and submucosa. Consequently, there is diversity in their clinical presentation, incidence at specific anatomic sites, biological behavior, hormone production, morphologic characteristics, and immunophenotype. Periampullary carcinoids are extremely rare and less then 100 patients have been reported in the world literature, that too mostly as case reports. We are reporting two cases of periampullary carcinoids, one of which presented with rare manifestation as gastrointestinal bleed and both are doing well after successful pancreatoduodenectomy.
Keywords: Carcinoid tumors, gastrointestinal bleed, periampullary
|How to cite this article:|
Somani A, Jain A K, Dixit V K. Periampullary carcinoid: An uncommon tumor at an unusual site. Indian J Cancer 2011;48:496-9
| » Introduction|| |
The carcinoid tumors are classified as neuroendocrine or amine precursor uptake and decarboxylation (APUD) tumors and are most common endocrine tumors comprising 50% of all NETs of the gastrointestinal tract.  They were first described in 1888 by Lubarsch, and the term "karzinoide tumoren" was used in 1907 by Oberndorfer.  They are classified according to the embryologic site of origin into foregut, including bronchus (20-30%), midgut (55-65%), and hindgut (5-10%).  Age-adjusted incidence rates for all types of carcinoids is 1.2-2.1/100,000 population/year  and it varies with gender, age, and race. However, in autopsies, the incidental finding of these tumors is much higher (up to 0.5-1%), with the main location being the small intestine.  The overall incidence of carcinoid tumors appears to have increased in the past decades, possibly as a result of improved detection rate. 
Carcinoid tumors of the ampulla of Vater are extremely rare. ,,, They most commonly present with obstructive symptoms causing jaundice and nonspecific abdominal discomfort. Preoperative diagnosis is difficult due to their relatively small size and submucosal location. Upper gastrointestinal endoscopy can show an obstructive tumor within periampullary region in most patients and the diagnosis can be confirmed by histology. Pancreatoduodenectomy or local excision is the standard curative modality. When necessary, excellent palliation may be achieved by surgery, radiation therapy, chemotherapy, or by pharmacologic therapy (somatostatin, interferon-alpha).
| » Case Reports|| |
A 36-year-old female presented with slowly progressive jaundice and cholestatic symptoms since 2 months. Except for icteric sclera and few scratch marks on body, rest of the physical examination was unremarkable. Abdominal ultrasonographic imaging showed dilated common bile duct (12.6 mm) and intrahepatic biliary radicals. An endoscopic retrograde cholangiopancreatography was performed which demonstrated a 2-cm smooth polypous mass with intact mucosa at the ampulla of Vater. Histological examination of biopsy specimen repeatedly failed to detect any tumor. The patient had undergone pancreatoduodenectomy, and subsequent histology results were consistent with carcinoid tumor.
Relevant laboratory data included the following values: hemoglobin, 11.8 g; prothrombin time, 14.9/14.2 sec; total bilirubin, 7.5; direct bilirubin, 6.1; albumin, 3.8 g/dl; alkaline phosphatase, 724 u/l; AST, 98; and ALT, 116. Stool examination demonstrated guaiac-negative, clay-colored stool. She was discharged on postoperative day 12 after an uncomplicated course. The final pathological finding was that of a 2.5 × 1.5 cm ampullary carcinoid, covered by intact mucosa, infiltrating the common bile duct and pancreatic duct into the submucosa and muscularis propria of the duodenum. Resected margins along with lymph nodes were free from tumor. Ten months after resection, the patient is doing well with no evidence of the disease.
A 48-year-old male was admitted in Dec 2000 with upper gastrointestinal bleed of one day. Physical examination was normal except for tachycardia (108/min) and exaggerated bowel sounds (8-10/min). Endoscopy revealed small ulcer in duodenal bulb and antral biopsy was positive for rapid urease test. With the diagnosis of peptic ulcer disease, patient was discharged on anti Helicobacter pylori medications. He was asymptomatic until December 2005 when he again developed two episodes of melena. Endoscopic study of the duodenum revealed a raised polypous tumor measuring 3 × 2 cm near the ampulla of Vater with ulcerated mucosal surface in center. Histology showed carcinoid tumor with immunohistochemistry-positive for neuron-specific enolase, chromogranin A, and synaptophysin. Contrast enhanced CT abdomen showed mild mural thickening with poor filling in second part of duodenum with no evidence of metastasis.
Relevant laboratory data included the following values: hemoglobin, 9.5 g; TLC, 8500; general blood picture showing mild anisocytosis, poikilocytosis and hypochromasia. Coagulation profile, liver and renal function tests were normal. 24 hours urinary 5-HIAA was 16 mg. The patient underwent pancreatoduodenectomy with extensive lymph node dissection. Fourteen days postoperatively he was discharged, and he had been doing well after 11 months of follow-up.
| » Discussion|| |
Periampullary carcinoid is a rare tumor ,,, with less than 100 cases, reported in world literature and that too mostly as case reports. Upper gastrointestinal bleed is a rare presenting feature (<3%) of periampullary carcinoid tumor  as seen in our second patient. The first patient presented with obstructive jaundice which is a common (>60%)  presentation in this disease. Other presenting features are upper abdominal discomfort (40%), weight loss (10%), and acute pancreatitis (5%).  A preoperative diagnosis of carcinoid tumor was established after histological and immunohistochemical analysis of endoscopic biopsy specimen in our patient who presented with gastrointestinal bleed, but was not possible in the patient who had common presenting symptom, i.e., jaundice. This discrepancy appears to be related to nature of lesion which was ulcerative in patient presenting with gastrointestinal bleed where biopsy from the edge of ulcer was diagnostic. However, those having smooth polypous mass covered by intact mucosa have deeper located tumor, where superficial biopsies may be unrewarding and burrow (tunnel) biopsies are needed to establish the histological nature of the tumor.  Lower success rates in establishing preoperative diagnosis (<15%) had been documented in previous reports as well. 
Although the second case had an upper gastrointestinal bleeding episode 5 years prior to the diagnosis, but chances of missing the carcinoid tumor at that stage was less likely. Since, during first bleeding episode, endoscopy showed small ulcer in duodenal bulb without any mass lesion or narrowing in duodenum. But during second bleeding episode endoscopy revealed a raised polypous tumor near the ampulla of Vater with ulcerated mucosal surface. In addition, the patient was completely asymptomatic for 5 years which seems unlikely with gastrin producing (G cell) carcinoid tumors. Moreover ampullary carcinoids often exhibit psammoma bodies and express somatostatin. ,
Attempts have been made to distinguish periampullary carcinoids from other periampullary tumors on features like lower mean age of presentation (5 th -6 th decade), longer duration of symptoms before diagnosis (>3 months), and associated neurofibromatosis 1 (>25%). ,, However, in both of our patients, age was less than 50 years, duration between onset of symptoms and diagnosis was less than 2 months, and none had cutaneous neurofibromas or cafe au lait spots.
The association between periampullary carcinoids and neurofibromatosis type 1 is well established with one-fourth of the periampullary carcinoid patients having neurofibromatosis type 1, ,, and vice versa up to 12% of neurofibromatosis type 1 patients develop an upper gastrointestinal carcinoid tumor, characteristically in the periampullary region (54%). Klein et al. suggested that patients with neurofibromatosis and abdominal pain or jaundice should be evaluated for the possibility of an ampullary tumor.
None of our patients were having features suggestive of carcinoid syndrome which is consistent with previous reports of rarity of carcinoid syndrome in ampullary carcinoids (<3%). , Both of our patients are surviving after ten and eleven months of follow-up which is expected in view of earlier reports of more then 90%, 5 year survival. 
In most instances, carcinoid tumors are discovered incidentally during surgery, endoscopy, or imaging studies. They may cause symptoms either through their mass effect (pain or luminal obstruction) or through their secretory products (carcinoid syndrome). Obstruction may be due to direct tumor growth or by the intense desmoplastic reaction and may cause dysphagia, abdominal pain, weight loss, changes in bowel function (e.g., constipation, diarrhea), or gastrointestinal bleeding. Systemic signs and symptoms (carcinoid syndrome) are usually not present unless secretory products (like serotonin, histamine, tachykinin, norepinephrine) are directly released into the systemic circulation.
Biochemical diagnosis is established by the elevation of plasma chromogranin A (CgA), serotonin, or urinary 5-hydroxyindoleacetic acid (5-HIAA), while anatomic localization is by octreoscan, computerized axial tomography (CAT) scan, Barium examinations, mesenteric angiography, MRI, PET scans or endoscopy/ultrasound. CT may show the characteristic "spokewheel" pattern secondary to desmoplasia. Histological identification is confirmed by CgA and synaptophysin immunohistochemistry. Primary therapy is surgical excision to avert local manifestations and decrease hormone secretion. Hepatic metastases may be amenable to cytoreduction, radiofrequency ablation, embolization alone, or with cytotoxics. Chemotherapy and radiotherapy have minimal efficacy. Intravenously administered receptor-targeted radiolabeled somatostatin analogs are of use in disseminated disease.
The overall 5-year survival rate for all carcinoid tumors (regardless of site or stage) ranges from 70% to 80%. ,, Stage of disease influences the prognosis significantly, with the best 5-year survival rate in localized disease (93%) and a poor 5-year survival rate with distant metastatic disease (20-30%). Tumor characteristics suggestive of increased metastatic risk are invasion into the muscularis propria, size greater than 2 cm, and presence of mitotic figures.  [Figure 1]
|Figure 1: (a) Histologic, (b) endoscopic, (c) barium meal follow through, and (d) CT appearance of periampullary carcinoid|
Click here to view
In periampullary carcinoids, size has no relation to metastatic potential, , unlike carcinoids in other areas. The tumor usually is approximately 2 cm in diameter (range 0.5-6 cm). In one large review, 44% of tumors larger than 2 cm and 46% of tumors smaller than 2 cm had metastasis to lymph nodes or liver.  The appropriate treatment guidelines for periampullary carcinoids are yet to evolve due to paucity of literature. However, given the propensity for patients with ampullary tumors smaller than 2 cm to have node-positive disease and considering the safety of pancreaticoduodenectomy in experienced hands, radical excision may be the treatment of choice to ensure complete resection. Also local resection is technically difficult if the ampulla is in proximity to the lesion.  However, long-term survival can also be achieved by local excision. Close follow-up after surgical resection is indicated as carcinoid tumors may metastasize. ,
Prognostically, carcinoid of the ampulla of Vater is an almost benign disease. Five-year survival is 90%, and the literature shows only 4 (6%) patients dying of metastatic and progressive tumor diseases. 
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