Small intestine & ampulla

Ampulla

Adenocarcinoma-ampulla


Editorial Board Member: Claudio Luchini, M.D., Ph.D.
Deputy Editors-in-Chief: Raul S. Gonzalez, M.D., Aaron R. Huber, D.O.
Felicia D. Allard, M.D.

Last author update: 12 October 2023
Last staff update: 12 October 2023

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PubMed Search: Ampullary adenocarcinoma

Felicia D. Allard, M.D.
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Cite this page: Allard FD. Adenocarcinoma-ampulla. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ampullaadenocarcinoma.html. Accessed May 19th, 2024.
Definition / general
  • Uncommon epithelial malignancy with glandular or mucinous differentiation that has an epicenter in the ampulla of Vater and displays an intestinal, pancreatobiliary or mixed phenotype
  • While advanced duodenal, distal common bile duct or pancreatic carcinoma may extend to involve the ampulla, only those malignancies centered on or circumferentially surrounding the ampulla are regarded as ampullary carcinomas
Essential features
  • Ampulla of Vater is a complex anatomical region that represents the junction of duodenal and pancreatobiliary type mucosa, resulting in a heterogenous group of malignancies that may arise from this site (Am J Surg Pathol 2012;36:1592)
  • Distinguishing ampullary / periampullary primaries from duodenal, distal common bile duct and pancreatic ductal primaries is based on careful gross examination to assess the tumor epicenter
  • Distinguishing intestinal from pancreatobiliary type tumors is an important prognostic factor; immunostains are helpful adjuncts to morphologic assessment (Int J Surg Pathol 2019;27:598)
ICD coding
  • ICD-O
    • 8020/3 - carcinoma, undifferentiated, NOS
    • 8140/3 - adenocarcinoma, NOS
    • 8144/3 - adenocarcinoma, intestinal type
    • 8163/3 - adenocarcinoma, pancreatobiliary type
    • 8490/3 - signet ring cell adenocarcinoma or poorly cohesive carcinoma
    • 8510/3 - medullary adenocarcinoma
    • 8211/3 - tubular adenocarcinoma
  • ICD-11: 2B80.20 - adenocarcinoma of small intestine, site unspecified
Epidemiology
Sites
  • Ampullary adenocarcinomas have 4 recognized subtypes (Am J Surg Pathol 2012;36:1592)
    • Periampullary carcinomas are exophytic masses that arise from the duodenal surface of the ampulla and engulf the ampullary orifice (~5%)
    • Intra-ampullary carcinomas arise from intra-ampullary papillary tubular neoplasms (IAPN, ~25%)
    • Ampullary ductal carcinomas arise from the portions of the distal common bile or pancreatic ducts located within the papilla of Vater and circumferentially involve the duct within the papilla (~15%)
    • Ampullary carcinomas, NOS are ulceronodular tumors located at the papilla of Vater that do not show the specific features of the 3 categories listed above (~55%)
Pathophysiology
  • Experts theorize that the tendency for small bowel adenocarcinomas as well as familial adenomatous polyposis related adenocarcinomas to occur in the ampullary region may be related to exposure to bile and pancreatic secretions
  • Known precursor lesions include (Am J Surg Pathol 2012;36:1592)
    • Intra-ampullary adenocarcinomas: intra-ampullary papillary tubular neoplasms
    • Periampullary adenocarcinoma: intestinal type adenoma
    • Ampullary ductal adenocarcinomas: some tumors show intraepithelial neoplasia; however, this is difficult to distinguish from colonization of the surface epithelium by invasive carcinoma cells
    • Ampullary carcinoma, NOS: precursor lesion unclear
Etiology
Clinical features
Diagnosis
  • Confirmation that a tumor is an ampullary carcinoma is best done on careful gross assessment of the resection specimen to determine the tumor epicenter (Am J Surg Pathol 2012;36:1592)
  • It is also important to look for precursor lesions that can support the origin of a periampullary tumor: pancreatic intraepithelial neoplasms for pancreatic cancer, intestinal adenoma for duodenal cancer, biliary intraepithelial neoplasms or intraductal papillary neoplasms for biliary (distal) cancer (see Pathophysiology) (Am J Surg Pathol 2012;36:1592)
Radiology description
  • Endoscopic retrograde cholangiopancreatography (ERCP) is the most useful endoscopic study for diagnosing ampullary carcinoma; it permits tumor identification, biopsy and biliary decompression with a single procedure (Am J Surg 1997;174:355)
  • MRI plus magnetic resonance cholangiopancreatography (MRCP) has shown good performance in differentiating between malignant and benign ampullary lesions (BMC Med Imaging 2019;19:77)
  • MRI diagnostic accuracy for ampullary lesions has been reported to be as high as 91.17% (BMC Med Imaging 2019;19:77)
Prognostic factors
Case reports
  • 11 year old boy presented with obstructive jaundice due to ampullary adenocarcinoma (youngest patient reported) (J Pediatr Surg 1997;32:636)
  • 45 year old man who presented with abdominal pain, nausea, vomiting and a fever was found to have ampullary adenocarcinoma (Cureus 2022;14:e29398)
  • 58 year old man with familial adenomatous polyposis presented with ampullary adenocarcinoma (Bratisl Lek Listy 2019;120:908)
  • 74 year old man who presented with decompensated cirrhosis and choledocholithiasis associated with an ampullary adenocarcinoma (Cureus 2023;15:e37566)
  • 77 year old man who presented with 2 rare synchornous primaries: ampullary adenocarcinoma and ileal gastrointestinal stromal tumor (World J Gastrointest Oncol 2022;14:2253)
Treatment
Gross description
  • Gross appearance depends on the region of the ampulla involved (Am J Surg Pathol 2012;36:1592)
    • Periampullary adenocarcinomas
      • Exophytic mass arising from the duodenal aspect of the ampulla
      • Vegetating mass around the ampulla that may obscure the ampullary orifice
      • Invasive component of the lesion may extend beyond the ampulla to involve the adjacent duodenal wall
      • Large tumors: average size of 4.7 cm with a 2.4 cm invasive component
      • 50% of cases have lymph node involvement at time of resection
    • Intra-ampullary adenocarcinomas
      • Arising from an intra-ampullary papillary tubular neoplasm
      • Appear as a mucosa covered bulge with a dilated ampullary orifice and bulky intraluminal growth within the ampulla
      • Average tumor size of 2.9 cm with an invasive component of 1.5 cm
      • 28% of cases have lymph node involvement at time of resection
    • Ampullary ductal adenocarcinomas
      • Appear as small concentric elevations and ulcerating retractions around the ampullary orifice
      • Upon bivalving the specimen along the duct, concentric thickening with or without stricturing of the intra-ampullary duct will be seen
      • Small tumor size: average of 1.9 cm
      • Low incidence of lymph node spread
    • Ampullary carcinoma, NOS
      • Tumor is grossly centered in the ampulla
      • Lacks the specific characteristics of the subtypes listed above
      • Often presents as an ulceration of the papilla with dilation of both the common bile duct and main pancreatic duct
  • Careful gross assessment of tumor extension into the duodenal wall and the pancreas or peripancreatic soft tissue as well as any major vessels is important for correct staging
  • Average gross size of tumors: 2.6 cm with invasive component measuring 1.8 cm (Am J Surg Pathol 2012;36:1592)
Gross images

Contributed by Felicia D. Allard, M.D. and Claudio Luchini, M.D., Ph.D.

Ampullary ductal carcinoma

Firm gray-white thickening

Microscopic (histologic) description
  • Majority are gland forming (tubular adenocarcinoma)
  • 60% show either intestinal or biliary phenotypes while 40% have a mixed phenotype (Mod Pathol 2016;29:1575)
    • Intestinal type: columnar cells with elongated, pseudostratified nuclei with scattered goblet cells and Paneth cells
    • Pancreatobiliary type: cuboidal cells with pleomorphism forming small glands in desmoplastic stroma
    • Mixed type: shows mix of intestinal and pancreatobiliary types
  • Nonglandular patterns include:
    • Mucinous adenocarcinoma: > 50% stromal mucin pools containing floating tumor cells / glands with an intestinal phenotype
    • Poorly cohesive cell carcinoma
    • Medullary carcinoma
    • Adenosquamous carcinoma: this extremely rare mixed tumor shows both morphologic and immunophenotypic evidence of both glandular and squamous differentiation (World J Surg Oncol 2015;13:287, World J Surg Oncol 2013;11:124)
    • Undifferentiated carcinoma
      • Undifferentiated carcinoma with osteoclast-like giant cells: tumor that is comprised of sarcomatoid appearing mononuclear cells and contains osteoclast-like giant cells
      • Undifferentiated carcinoma with rhabdoid phenotype: discohesive tumor cells show abundant eosinophilic intracytoplasmic rhabdoid bodies and are present in a myxoid matrix (Am J Surg Pathol 2016;40:544)
  • Histologic features by subtype (Am J Surg Pathol 2012;36:1592)
    • Intra-ampullary adenocarcinomas
      • Majority of the lesion often consists of the precursor intra-ampullary papillary tubular neoplasm
      • Majority show an intestinal phenotype
      • Growth patterns include papillary, tubular and tubulopapillary
      • Noninvasive precursor component may display a different epithelial phenotype than the invasive component
    • Periampullary adenocarcinomas
      • Majority are intestinal type
      • May show mucinous or signet ring cell patterns
    • Ampullary ductal carcinomas
      • Pancreatobiliary type
      • May show focal micropapillary or sarcomatoid areas
    • Ampullary carcinoma, NOS
      • Lacks the specific characteristics of the above subtypes
      • Heterogenous histologic types: 45% pancreatobiliary type, 27% intestinal type, 28% mixed or other type
Microscopic (histologic) images

Contributed by Felicia D. Allard, M.D.

Intestinal type adenocarcinoma

Signet ring cell morphology

Adenocarcinoma arising from IPTN

Ampullary duct carcinoma


Pancreaticobiliary phenotype

CDX2 pancreatobiliary phenotype

CK7 pancreatobiliary phenotype

CK20 pancreatobiliary phenotype

Virtual slides

Images hosted on other servers:

Forcep biopsy periampullary mass

Cytology description
  • Cellular to moderately cellular preparations
  • Malignant cells when grouped are typically crowded and present in 3 dimensional clusters
  • Single pleomorphic cells are often present
  • Nuclei are typically enlarged and irregular with an increased N:C ratio, coarse chromatin and prominent nucleoli are often present
  • Necrosis can occasionally be seen (J Clin Pathol 2001;54:449, Cancer 2005;105:289)
  • In one study, 13/35 ampullary adenocarcinomas were identified via EUS FNA sampling (Cancer 2005;105:289)
Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Pancreas, small bowel and distal common bile duct, pancreatoduodenectomy:
    • Ampullary adenocarcinoma, pancreatobiliary type, poorly differentiated, invasive into the pancreatic head (pT3a) (see synoptic report)
    • 3 of 15 lymph nodes positive for carcinoma and 1 tumor deposit (3/15, pN1)
    • Perineural as well as extensive lymphovascular and large vessel invasion is present
    • Resection margins are free of high grade dysplasia and carcinoma (closest approximation: 0.3 cm to retroperitoneal margin)
    • Use ampulla pTMN for staging
Differential diagnosis
  • Intra-ampullary papillary tubular neoplasm:
    • No invasion present
  • Adenomatous changes in submucosal glands / ductules simulating invasion:
    • No desmoplastic stroma or single cell invasion present to indicate a truly invasive process
    • Dysplastic ducts will have round, regular contours and be present in a lobular configuration in most cases
  • Extrahepatic cholangiocarcinoma:
    • Tumor may show concentric thickening of the distal common bile duct but tumor will not be centered in the ampulla
  • Duodenal adenocarcinoma:
    • Tumor may also arise in intestinal type adenomatous mucosa near the ampullary orifice and extend to involve the ampulla but the tumor will not be centered around the orifice
Board review style question #1

The tumor shown above most likely comprises which of the following epithelial types?

  1. Gastric
  2. Intestinal
  3. Pancreatobiliary
  4. Squamous
Board review style answer #1
C. Pancreatobiliary. The image shows a mass arising at the convergence of the main pancreatic duct and the duodenal mucosal surface, circumferentially surrounding the main pancreatic duct with depression of the duodenal surface. No mass forming lesion is present within the lumen of the duct. Answers A, B and D are incorrect because the gross image is most consistent with an ampullary ductal carcinoma, and the majority of ampullary ductal carcinomas show a pancreatobiliary phenotype, histologically.

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Reference: Adenocarcinoma - ampulla
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