Ampullary Region: Adenomas and Dysplasia

Ampullary Region

Adenomas and Flat Dysplasia

• Ampullary adenomas can occur sporadically or in the context of familial adenomatous polyposis.
• Historically, invasive carcinoma was almost always present at the base of ampullary adenomas upon exploration.
• Endoscopic procedures have improved early detection and characterization of these lesions.
• Ampullary adenomas can be tubular or villous, resembling colorectal adenomas.
• Paneth cells and neuroendocrine cells are commonly found in ampullary adenomas.
• The risk of invasive adenocarcinoma increases with the size of the adenoma.
• Endoscopic resection has largely replaced pancreaticoduodenectomy for managing ampullary adenomas.
• Prognosis is excellent with complete excision.
• Flat dysplasia in the ampullary region is not well-characterized due to lack of symptoms or being overrun by adenocarcinoma before resection.

Intra-ampullary Papillary-Tubular Neoplasm (IAPN)

• IAPNs are preinvasive, mass-forming neoplasms located primarily within the ampulla.
• More than 75% of the lesion must be within the ampullary channel and/or distal segments of the pancreatic or common bile duct.
• IAPNs have minimal involvement of the duodenal mucosa or proximal pancreatic/common bile ducts.
• The epithelium of IAPNs can be intestinal or gastric/pancreatobiliary type.
• IAPNs exhibit varying degrees of papillary or tubular growth patterns.
• Approximately 75% of IAPNs are associated with an invasive component.

Ampullary Carcinoma

• Ampullary carcinoma is a malignant epithelial tumor centered in the ampulla of Vater.
• It can be challenging to differentiate ampullary carcinoma from adenocarcinomas of the distal common bile duct, periampullary duodenum, pancreatic head, and true ampulla.
• Current classification divides ampullary carcinomas into four groups based on anatomic location:
  • Intra-ampullary carcinomas associated with IAPNs
  • Ductal ampullary carcinomas
  • Periampullary/duodenal carcinomas
  • Ampullary carcinoma not otherwise specified (N.O.S.)
• Adenocarcinomas associated with IAPNs have the best prognosis.
• Ductal type carcinomas exhibit constrictive, stenotic growth in the distal common bile duct or pancreatic duct at the ampulla.
• Ductal type carcinomas have the worst prognosis among ampullary carcinomas but are less aggressive than pancreatic ductal adenocarcinomas.
• Periampullary/duodenal carcinomas bulge into the duodenal lumen with minimal intra-ampullary extent, and typically involve the ampullary orifice eccentrically.
• Ampullary carcinomas N.O.S. are located at the papilla of Vater but do not fit the characteristics of the other three types.
• True ampullary carcinomas tend to have a better prognosis than carcinomas of the pancreas, common bile duct, and duodenum with secondary ampullary involvement.
• Underlying pancreatic head adenocarcinomas and other non-ampullary primary tumors may colonize the ampullary mucosa, leading to diagnostic confusion.
• Most patients with ampullary carcinoma are over 60, with a slight male predominance.
• Some cases are associated with familial adenomatous polyposis and neurofibromatosis type 1.
• Periampullary/duodenal tumors bulge into the duodenal lumen.
• Tumors associated with IAPNs tend to fill the ampullary channel.
• Ductal type tumors cause plaque-like or stenotic growth in the distal ducts.
• Microscopically, nearly all ampullary malignant tumors are adenocarcinomas.
• Ampullary adenocarcinomas are often poorly differentiated, with intestinal, pancreatobiliary, or mixed phenotypes.
• Morphologic variations include examples with a prominent Paneth cell component, adenosquamous carcinoma, micropapillary carcinoma, and cases exhibiting hepatoid differentiation.
• Tumors with pancreatobiliary appearance are typically CK7+/CK20-, while those with intestinal morphology are usually CK7-/CK20+.
• MUC2 and CDX2 positivity is typical of intestinal-type tumors but not pancreatobiliary-type.
• TP53 mutations are common, with corresponding accumulation of the abnormal product detected immunohistochemically.
• DPC4 mutations are rare, and only a minority (30%-40%) harbor KRAS gene mutations.
• Ampullary carcinoma can invade adjacent structures, including duodenal mucosa, duodenal wall, pancreas, and common bile duct.
• Perineural invasion may be present.
• Regional lymph node metastases are found in 35%-50% of cases.
• The prognosis of ampullary carcinoma is better than that of pancreatic carcinoma and bile duct carcinoma.
• Overall 5-year survival rate has risen to 40%-50% or higher in recent studies.
• Survival is higher in the absence of lymph node metastases.
• Stage of disease is the most important prognostic indicator.
• Other adverse prognostic factors include pancreatobiliary histologic subtype and tumor budding.
• The treatment of choice is the Whipple procedure.
• Ampullectomy may be considered in patients with small, superficial carcinomas or those who are poor operative risks.

Neuroendocrine Neoplasms

• Well-differentiated neuroendocrine neoplasms and poorly differentiated NEC can occur in the ampullary region.
• Ampullary carcinoid tumors are more likely to be associated with neurofibromatosis type 1, unlike those in the rest of the duodenum.
• Mixed adenocarcinoma/NET and mixed acinar/NECs have been rarely reported.

Miscellaneous Tumors and Tumorlike Lesions

• Other tumors and tumor-like conditions in the ampullary region include:
  • Adenomyoma
  • Adenomyomatous hyperplasia (thought to be a sequela of chronic papillitis)
  • GISTs
• Gangliocytic paraganglioma is almost exclusively found in this location.
• Primary malignant lymphomas have been rarely described.
• Fibrosis of the papilla of Vater is sometimes diagnosed in patients with right upper abdominal pain, with a "pinpoint ampullary opening" found at surgery.
• Inflammatory or fibrotic changes in the papilla of Vater are usually associated with chronic gallbladder or pancreatic disease, or previous surgical/endoscopic manipulation.
• Patients with sclerosing IgG4 disease may have involvement of the ampulla.