Small intestine & ampulla
Ampulla
Adenocarcinoma-ampulla

Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Felicia D. Allard, M.D.

Topic Completed: 28 April 2020

Minor changes: 14 July 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: ampullary adenocarcinoma [title]

Felicia D. Allard, M.D.
Page views in 2019: 8,452
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Cite this page: Allard FD. Adenocarcinoma-ampulla. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/ampullaadenocarcinoma.html. Accessed September 23rd, 2020.
Definition / general
  • Uncommon epithelial malignancy with glandular or mucinous differentiation that has an epicenter in the ampulla of Vater and displays an intestinal or pancreatobiliary 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: 8140/3 - adenocarcinoma, NOS
  • ICD-O: 8144/3 - adenocarcinoma, intestinal type
  • ICD-O: 8163/3 - adenocarcinoma, pancreatobiliary type
  • ICD-O: 8490/3 - signet ring cell adenocarcinoma or poorly cohesive carcinoma
  • ICD-O: 8510/3 - medullary adenocarcinoma
  • ICD-O: 8211/3 - tubular adenocarcinoma
  • ICD-O: 8020/3 - carcinoma, undifferentiated, NOS
  • ICD-11: 2B80.20 - adenocarcinoma of small intestine, site unspecified
Epidemiology
Sites
  • Ampullary adenocarcinomas have four 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 (~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 not otherwise specified are ulceronodular tumors located at the papilla of Vater that do not show the specific features of the above three categories (~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 not otherwise specified: 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
Radiology description
  • 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 presenting with obstructive jaundice due to ampullary adenocarcinoma (youngest patient reported) (J Pediatr Surg 1997;32:636)
  • 54 year old woman presenting with a skull metastasis 5 years after resection of ampullary adenocarcinoma (J Neurooncol 2009;95:141)
  • 58 year old man with familial adenomatous polyposis presents with ampullary adenocarcinoma (Bratisl Lek Listy 2019;120:908)
  • 61 year old man presenting with parotid metastasis 2 years after resection of ampullary adenocarcinoma (J Gastrointest Cancer 2007;38:95)
  • 78 year old woman presenting with jaundice was found to have signet ring cell carcinoma of the ampulla (JOP 2013;14:190)
Treatment
  • Management of early stage disease is primarily surgical, typically pancreatoduodenectomy (Whipple procedure) followed by adjuvant chemoradiation (Am Soc Clin Oncol Educ Book 2014:112)
  • Unresectable disease is treated systemically with gemcitabine combined with a platinum compound plus radiation therapy (Am Soc Clin Oncol Educ Book 2014:112)
  • Small retrospective studies have suggested that patients with pancreatobiliary type carcinomas may benefit from gemcitabine therapy while those with intestinal type tumors may benefit from 5-fluorouracil (5-FU) based regimens (BMC Cancer 2008;8:170, Am J Surg Pathol 2014;38:1371)
  • A large, multicenter European study group for pancreatic cancer (ESPAC)-3 periampullary randomized controlled trial demonstrated no significant overall survival benefit from adjuvant chemotherapy (fluorouracil or gemcitabine) (JAMA 2012;308:147)
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 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 with bulky intraluminal growth within the ampulla
      • Average tumor size of 2.9 cm with invasive component 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 1.9 cm
      • Low incidence of lymph node spread
    • Ampullary carcinoma NOS:
      • Tumor is grossly centered in the ampulla
      • Lack the specific characteristics of the above subtypes
      • Often present 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.

Ampullary ductal carcinoma

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: show 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, comprised of sarcomatoid appearing mononuclear cells, 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:
      • The majority of the lesion often consists of the precursor intra-ampullary papillary tubular neoplasm
      • The majority show an intestinal phenotype
      • Growth patterns include papillary, tubular and tubulopapillary
      • The 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:
      • Lack 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 nuclear to cytoplasmic 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 one 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



This tumor is most likely comprised of which of the following epithelial types?

  1. Gastric
  2. Intestinal
  3. Pancreatobiliary
  4. Squamous
Board review answer #1
C. Pancreatobiliary

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Reference: Adenocarcinoma
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