Ampullary neuroendocrine tumor presenting with biliary obstruction and gastric outlet obstruction.

Neuroendocrine tumors of the ampulla of Vater are extremely rare cause of extrahepatic biliary obstruction and further rarer cause of duodenal obstruction, and only a few cases have been reported in the literature. Herein we report a case of ampullary neuroendocrine tumor in a 75-year-old woman who presented with biliary obstruction and gastric outlet obstruction palliated with metal biliary and duodenal stenting with relief of jaundice and vomiting at 1 month of follow-up.

INTRODUCTION

Neuroendocrine tumor (NET) is defined as epithelial neoplasm that shows greater or equivalent neuroendocrine differentiation by conventional histologic, immunohistochemical, ultrastructural, and/or biochemical evaluation. Neuroendocrine tumors of the ampulla of Vater are extremely rare. They account for less than 0.3% of all gastrointestinal neuroendocrine tumors and less than 2% of ampullary malignancies.[1] Only 105 cases of neuroendocrine tumors have been reported in the literature.[2] In 2000, the World Health Organization (WHO) revised the histopathologic classification system for gastroenteropancreatic neuroendocrine tumors.[34] The term carcinoid was replaced with neuroendocrine tumor, which connotes a broader spectrum of histologic appearance and behavior and can be further subcategorized into benign, potentially malignant, and malignant. Jaundice is the predominant symptom followed by pain and weight loss. We report a case of ampullary neuroendocrine carcinoma presenting with biliary obstruction and gastric outlet obstruction palliated adequately with metal biliary and duodenal stenting.

CASE REPORT

The patient, 75-year-old woman, a hypertensive for 2 years, on regular treatment, along with hearing impairment, presented with high-grade fever for 4 months. She developed painless progressive jaundice with severe pruritus for 20 days. She also had anorexia with a weight loss of about 10 kg in the previous 4 months. There was no history of gastrointestinal bleed or vomiting. Examination showed deep icterus, no lymphadenopathy. Abdomen showed soft hepatomegaly 3 cm below costal margin. Rest of the systemic examination was normal. Laboratory parameters showed conjugated hyperbilirubinemia (total, 17.0 mg/dL; normal, 1 mg/dL; conjugated, 9.0 mg/dL) with raised alkaline phosphatase(ALP) (954 IU/mL; normal, 150 IU/ mL). Contrast-enhanced computered tomography (CECT) of abdomen showed periampullary growth (3 cm × 3 cm), bilobar intrahepatic biliary radical dilatation, and dilated common bile duct (CBD) till lower end [Figure 1] with no evidence of local or distant spread. The patient was taken up for endoscopic retrograde cholangiography (ERC) for preoperative biliary drainage. Side viewing endoscopy (SVE) showed a large periampullary growth with duodenal narrowing at the level of papilla, biopsy was taken and a plastic stent was placed in the CBD. Post-ERC, the patient was asymptomatic but ultrasonography (USG) showed bilobar intrahepatic biliary radical dilatation and dilated CBD. Repeat ERC with endonasal biliary drainage (ENBD) was done. Postprocedure liver function tests (total bilirubin, 9.7; ALP, 768 IU/mL) improved but USG again showed bilobar intrahepatic biliary radical dilatation with dilated CBD, no pneumobilia. However, ENBD drained about 1000–1200 mL/day. Ampullary biopsy showed atypical cells, moderately pleomorphic, and high nuclear–cytoplasmic ratio, round nuclei, fine chromatin, inconspicuous nucleoli, granular cytoplasm, and significant mitotic figures [Figure 2]. Immunohistochemistry done for chromogranin, synaptophysin, and cytokeratin were positive [Figure 3a–c]. She was discharged with the plan of Whipple's procedure when bilirubin decreased to less than 5 mg/dL. Three weeks later she was readmitted with repeated bouts of nonbilious vomiting, in dehydrated state. She was resuscitated with intravenous fluids. USG abdomen showed bilobar intrahepatic biliary radical dilatation, dilated CBD, multiple hypoechoic space occupying lesions in both lobes of liver. Fine-needle aspiration cytology of these lesions was suggestive of disseminated disease and the patient was considered for palliation. endoscopic retrograde cholangiopancreatography (ERCP) was attempted for palliative biliary metal stenting but it revealed a large periampullary growth obstructing almost whole of the duodenal lumen at the level of papilla and prior biliary stent could not be accessed. Through percutaneous transhepatic route, biliary metal stent was placed reaching distal to the duodenal obstruction in the third part of duodenum for adequate biliary drainage. Also 12 cm Wall flex duodenal metal stent was placed to palliate the duodenal obstruction [Figure 4]. The patient tolerated the procedures well. Postprocedure USG showed adequate biliary decompression. She was discharged in a stable condition and is asymptomatic at 1 month of follow-up.

Figure 1

Contrast-enhanced computed tomography showing dilated common bile duct (black arrow), dilated biliary radicals with a mass in the periampullary region (white arrow)

Figure 2

Ampullary biopsy section shows tumor arranged in sheets and cords infiltrating into the lamina and submucosa. Tumor cells are round to irregular having moderately pleomorphic nuclei, stippled chromatin, prominent nucleoli, and scant to moderate amount of the cytoplasm (hematoxylin and eosin, ×400 magnification)

Figure 3

(a) Immunohistochemistry showed chromogranin positivity in the tumor cells (×400 magnification). (b) Immunohistochemistry revealed strong synaptophysin positivity in the tumor cells (×400 magnification). (c) Tumor cells are positive for cytokeratin on immunohistochemical staining (×400 magnification)

Figure 4

X-ray abdomen showing biliary (black arrow) and duodenal (white arrow) metal stents with a percutaneous drain

DISCUSSION

The neoplasm of the disseminated neuroendocrine cell system of the gastrointestinal tract have been known as carcinoids; however, since these tumors display a broad morphologic and biological spectrum, this is inappropriate.[5] The latest World Health Organization (WHO) classification, published in 2000 recommended to distinguish between (1) well-differentiated endocrine tumors (carcinoids); (2) well-differentiated endocrine carcinomas (malignant carcinoids); and (3) poorly differentiated endocrine carcinomas (small cell carcinomas).[6] Whereas the latter 2 categories clearly represent malignant neoplasms, well-differentiated endocrine tumors may clinically either behave as benign or malignant. Our patient had well-differentiated endocrine carcinoma. As a rule, nonangioinvasive tumors that do not exceed a size of 1 cm and show 2 or less mitoses per 10 high-power fields are considered benign, whereas the others harbor an increased risk of clinical malignancy.[6]

Endocrine neoplasms only rarely occur at the ampulla of Vater, consisting of mostly carcinoids and malignant carcinoids, as well as a few cases of poorly differentiated endocrine carcinomas (small cell carcinomas).[3478] In a total of 105 patients published in the literature, the average age was 48.6 years, and the gender ratio of female to male was 2.8:1.[19-14] Jaundice is the predominant symptom (53%) at the time of admission to hospital, followed by pain (24.6%) and weight loss (3.7%). Another rare but specific symptom could be acute pancreatitis (6.0%).[2] Our patient presented with jaundice but later developed gastric outlet obstruction, which is quite a rare presentation of ampullary neuroendocrine tumor and has not been reported earlier. Carcinoids of the ampulla of Vater are often associated with the von Recklinghausen disease (in 25.9% of all cases of the literature); however, in our case von Recklinghausen disease was not associated. The reported tumor sizes are between 0.2 and 9.5 cm in diameter and in our case the tumor size was about 5 cm. In 58% of all reported patients with ampullary carcinomas the Whipple procedure was the favorite approach for therapy. In an average follow-up time for all patients in the literature of 25.3 months, 46.6% developed metastasis. Our patient had disseminated disease within 1 month of follow up and was unresectable and considered only for palliation.

In contrast to patients with carcinoid tumors in the jejunum and ileum, patients with carcinoid tumors of the ampulla of Vater are very often free of clinical and laboratory findings that belong to the carcinoid syndrome. Only 2 of 71 patients (2.8%) with papillary carcinoids reviewed in the literature had a history of flushing, diarrhea, and asthma.[2] Our patient had no features suggestive of carcinoid syndrome. Immunohistochemically, other hormonal markers such as chromogranin (92%), neuron-specific enolase, synaptophysin, and cytokeratin (all in 100% of the cases) have been studied in a few cases, but the number of patients evaluated is too small to make these markers significantly reliable for diagnostic methods.[2] Chromogranin, synaptophysin, and cyokeratin stains were positive in our patient.

In the literature the preoperative diagnosis of carcinoid tumor was correct in only 14% of the patients (10 of 71).[2] Duodenoscopy in combination with ERCP is the diagnostic method of choice, and often deeper biopsies are needed to identify carcinoid tumors. Endosonography, CT, or magnetic resonance imaging completes the staging approach of this tumor. Somatostatin receptor scintigraphy is a sensitive diagnostic method to detect endocrine gastrointestinal tumors and their metastases. Diagnosis in our case was made by biopsy from the ampulla by SVE.

Thus our case of ampullary neuroendocrine tumor presented with uncommon manifestation of biliary obstruction and duodenal obstruction, and was unresectable because of liver secondaries and was palliated percutaneously with biliary stenting and endoscopically with duodenal stenting with adequate symptom relief at 1 month of follow-up.