Ampullary adenomas: Clinical manifestations and diagnosis

INTRODUCTION — Benign neoplasms of the ampulla of Vater are rare, representing less than 10 percent of periampullary neoplasms [1,2]. Adenomas are the most common benign lesions of the ampulla but have the potential to undergo malignant transformation to ampullary carcinomas [1,3-19]. This topic will review the clinical manifestations and diagnosis of ampullary adenomas. The management of ampullary adenomas and the clinical presentation, diagnosis, and management of ampullary cancer are discussed elsewhere. (See "Ampullary adenomas: Management" and "Ampullary carcinoma: Epidemiology, clinical manifestations, diagnosis and staging" and "Ampullary carcinoma: Treatment and prognosis".)

EPIDEMIOLOGY — Ampullary adenomas, also referred to as papillary adenomas because they arise from the mucosa of the major papilla, are detected in 0.04 to 0.12 percent of individuals in autopsy series [8,20,21]. Ampullary adenomas can occur sporadically, or in the setting of adenomatous polyposis syndromes, including familial adenomatous polyposis and MUTYH-associated polyposis. Sporadic ampullary adenomas are usually diagnosed in patients older than 40 years of age and most commonly in their seventies. In contrast, patients with ampullary adenomas in the setting of an adenomatous polyposis syndrome are frequently diagnosed decades earlier in the setting of a surveillance program rather than because of symptoms [22]. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis", section on 'Extracolonic manifestations' and "MUTYH-associated polyposis", section on 'Extracolonic manifestations'.)

CLINICAL FEATURES — Clinical features are a consequence of a mass-effect of the adenoma compressing and impeding biliary or pancreatic outflow.

Clinical presentation — Jaundice is the most common presenting symptom and is present in 50 to 75 percent of patients [3,23-26]. It is usually painless or accompanied by a vague or dull ache in the epigastrium [3]. Patients rarely have pruritus and infrequently develop cholangitis [27]. Other symptoms include biliary colic, nausea, and vomiting [3,25,28]. Less commonly, patients can present with acute pancreatitis, iron deficiency anemia, and overt upper gastrointestinal bleeding [23,28-32].

Imaging features — Patients with ampullary adenomas usually have evidence of biliary ductal dilation on imaging of the abdomen performed for evaluation of obstructive jaundice. Up to 25 percent of patients have associated common bile duct stones secondary to cholestasis [33]. Abdominal imaging is not diagnostic for an ampullary adenoma as it does not permit direct luminal visualization of the papillary aspect of the ampulla to provide access for tissue acquisition for histopathology. (See 'Diagnosis' below and "Diagnostic approach to the adult with jaundice or asymptomatic hyperbilirubinemia", section on 'Evaluation for intrahepatic cholestasis'.)

●Abdominal ultrasound – An ampullary adenoma is rarely visualized on abdominal ultrasound as gas frequently obscures the distal bile duct, ampulla, and pancreas [34]. In one study, only 10 of 127 ampullary masses were detected by ultrasound [35]. Abdominal ultrasound may demonstrate bile duct dilation or incidental common bile duct stones. (See "Ampullary carcinoma: Epidemiology, clinical manifestations, diagnosis and staging", section on 'Transabdominal ultrasonography'.)

●Abdominal CT scan – Abdominal CT findings of an ampullary adenoma include an ampullary soft-tissue mass, an irregular margin of the ampulla, extrahepatic biliary duct dilatation, and pancreatic duct dilatation [36]. Abdominal CT is more sensitive as compared with abdominal ultrasound at detecting a mass obstructing the distal common bile duct. However, its sensitivity usually does not permit the visualization of small ampullary neoplasms within the duodenal lumen [37]. With the introduction of multidetector CT and improved spatial resolution, the sensitivity and specificity of CT for detection of ampullary adenomas are 48 and 86 percent, respectively [36].

●Magnetic resonance cholangiopancreatography – On magnetic resonance cholangiopancreatogram, ampullary adenomas typically manifest as a filling defect or focal stricture at the distal end of a dilated common bile duct. (See "Ampullary carcinoma: Epidemiology, clinical manifestations, diagnosis and staging", section on 'Magnetic resonance cholangiopancreatography and percutaneous transhepatic cholangiography'.)

DIAGNOSIS — An ampullary adenoma may be detected on endoscopic retrograde cholangiopancreatography (ERCP) in patients with obstructive jaundice and extrahepatic bile duct obstruction on abdominal imaging or on upper endoscopy performed for evaluation of unrelated symptoms or surveillance of an adenomatous polyposis syndrome. The diagnosis is usually established on histopathology obtained by duodenoscopy and biopsy. However, only complete resection of an ampullary adenoma can definitively exclude a focus of malignancy.

We reserve the use of endoscopic ultrasound (EUS) for large ampullary adenomas (≥2 cm) or those with endoscopic features of malignancy. Endoscopic features suggestive of an underlying ampullary carcinoma include:

●Induration and rigidity of the papilla on probing

●Mucosal ulceration and friability

●Submucosal mass effect that leaves the overlying mucosa intact due to tumor extension into the duodenal wall

Duodenoscopy and biopsy — A side-viewing endoscope can directly visualize the ampulla. We perform at least six biopsies of the ampulla to improve accuracy [28,38,39]. Biopsy forceps should be directed away from the pancreatic duct orifice as the resultant papillary edema can cause acute pancreatitis [40]. In patients undergoing an ERCP, biopsies of the ampulla should be preferentially obtained after sphincterotomy. We also obtain intraductal biopsies of the ampullary segment of the common bile duct or pancreatic duct.

Biopsies obtained during duodenoscopy cannot reliably exclude the presence of a malignant focus within an ampullary adenoma. Foci of adenocarcinoma are reported in 15 to 60 percent of ampullary adenomas [13,41-44]. False-negative results from endoscopic biopsies have been described in 16 to 60 percent of patients with carcinoma, with diagnostic accuracy rates of 45 to 80 percent in several reports [14,42,43,45-47].

Investigational techniques to improve diagnostic accuracy include immunohistochemical staining for the p53 tumor suppressor gene, polymerase chain reaction analysis of tumor DNA for K-ras gene mutations, and the addition of flow cytometry to assess aneuploidy [1,8,44,48-50].

Endoscopic ultrasound in selected patients — Fine-needle aspiration of the ampulla, papilla, and surrounding deeper structures, including local lymph nodes, can be obtained during an endoscopic ultrasound. However, a negative result does not exclude the presence of a malignant focus within an adenoma.

The role of EUS is largely in preoperative staging of ampullary carcinomas rather than in the detection of benign ampullary neoplasms and is discussed in detail separately. (See "Ampullary carcinoma: Epidemiology, clinical manifestations, diagnosis and staging", section on 'Endoscopic ultrasonography'.)

Differential diagnosis — The differential diagnosis of ampullary adenomas includes benign lesions of the ampulla (eg, hemangiomas, leiomyomas, leiomyofibromas, lipomas, lymphangiomas, and mixed endocrine neurogenic tumors) and ampullary carcinoma. These entities can be distinguished based on histology. (See "Epidemiology, clinical features, and types of small bowel neoplasms".)

POST-DIAGNOSTIC EVALUATION — Individuals with ampullary adenomas should be advised to undergo colonoscopy to screen for colorectal neoplasms. Limited data suggest that even in the absence of an adenomatous polyposis syndrome, individuals with ampullary adenomas are at increased risk for the development of colorectal neoplasia [51,52].

Individuals with an ampullary adenoma and colorectal adenomas or extracolonic features of an adenomatous polyposis syndrome (eg, desmoid tumors, thyroid cancer, congenital hypertrophy of the retinal pigment epithelium, epidermal cysts, or osteomas) should undergo genetic evaluation. Genetic evaluation of familial adenomatous polyposis syndrome and MUTYH-associated polyposis is discussed in detail separately. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis", section on 'Diagnosis' and "MUTYH-associated polyposis", section on 'Diagnosis'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ampullary neoplasms".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Ampullary adenomas are detected in 0.04 to 0.12 percent of individuals in autopsy series. Ampullary adenomas can occur sporadically, or in the setting of an adenomatous polyposis syndrome including familial adenomatous polyposis and MUTYH-associated polyposis. (See 'Epidemiology' above.)

●Clinical features – The most common presenting symptom is jaundice, which is present in 50 to 75 percent of patients. Other symptoms include biliary colic, nausea, vomiting, and weight loss. Less commonly, patients can present with acute pancreatitis, iron deficiency anemia, or overt upper gastrointestinal bleeding. (See 'Clinical presentation' above.)

●Imaging findings – Patients with ampullary adenomas usually have evidence of biliary ductal dilation on imaging of the abdomen performed for evaluation of obstructive jaundice. Abdominal imaging cannot definitively diagnose an ampullary adenoma as it does not permit direct luminal visualization of the papillary aspect of the ampulla or provide access for tissue acquisition via direct forceps biopsy. (See 'Imaging features' above.)

●Diagnosis – An ampullary adenoma may be detected on endoscopic retrograde cholangiopancreatography in patients with obstructive jaundice and extrahepatic bile duct obstruction on abdominal imaging or on upper endoscopy performed for evaluation of unrelated symptoms or surveillance of an adenomatous polyposis syndrome. The diagnosis is usually established on histopathology obtained by duodenoscopy and biopsy. However, only complete resection of an ampullary adenoma can definitively exclude a focus of malignancy. (See 'Diagnosis' above.)

We reserve the use of endoscopic ultrasound for large ampullary adenomas (≥2 cm) or those with endoscopic features of malignancy. Endoscopic features suggestive of an underlying ampullary carcinoma include:

•Induration and rigidity of the papilla on probing

•Mucosal ulceration

•Submucosal mass effect that leaves the overlying mucosa intact due to tumor extension into the duodenal wall

●Colorectal cancer screening – Individuals with ampullary adenomas should be advised to undergo colonoscopy to screen for a colorectal neoplasm. Individuals with a history of colorectal adenomas and an ampullary adenoma should undergo assessment for adenomatous polyposis syndromes. (See 'Post-diagnostic evaluation' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Gregory B. Haber, MD, for his past contributions as an author to prior versions of this topic review.