Invasive Adenocarcinoma of the Ampullary Region

Epidemiology and Etiology:

Common sites:

Gross features:

Histologic features:

• Tubular growth pattern (85-95%)
• Classified according to the predominant component as below
• Intestinal-type adenocarcinoma:
• Simple or cribriformed tubular glands (similar to adenoCA of thte colon)
• Columnar cells with pseudostratification
• Oval or elongated nuclei
• Varying degrees of atypia
• Variable number of mitotic figures
• Adenoma associated (most)
• adenoCA arising in adenomas usually smaller and have a better prognosis
• Goblet cells interspersed with the columnar cells maybe
• Paneth cells and endocrine cells present (rarely)
• Dirty-type necrosis (not as common as in the colon)
• Pancreatobiliary-type adenocarcinoma:
• Similar phenotype to pancreatic ductal or extrahepatic bile duct carcinoma
• Simple or branching glands
• Small solid clusters in less differentiated tumours
• Abundant desmoplastic stroma
• Single layer of cuboidal or columnar cells
• Without pseudostratification usually
• Nuclei rounder than in intestinal type adenoCA
• Greater cytological atypia than intestinal type (in general)
• More mitotic figures than intestinal type (in general)
• Micropapillary pattern (focally in < 5% of pancreatobiliary-type adenoCA)
• Associated intestinal-type adenoma or noninvasive papillary neoplasm (occasionally)
• Mixed intestinal and pancreatobiliary phenotype (small number)
• Adenosquamous carcinoma:
• Clear cell carcinoma:
• Hepatoid adenocarcinoma:
• High-grade neuroendocrine carcinoma and mixed carcinomas:
• Small cell CA may arise in the ampulla
• Large cell neuroendocrine carcinoma may arise in the ampulla
• Both types of high-grade NEC can arise in association with intestinal-type adenomas
• Histologic features resemble those of their pulmonary counterparts
• Mitotic rate > 20 per 10 high power fields by definition
• Mucinous adenocarcinoma:
• Invasive papillary adenocarcinoma:
• Signet ring cell carcinoma:
• Squamous cell carcinoma:
• Undifferentiated carcinoma:
• Undifferentiated carcinoma with osteoclast-like giant cells:
• Establishing the organ of origin can be difficult given location next to pancreas, duodenum, and CBD
• If bulk of the mass is in the pancreas, the neoplasm is recognizable as a pancreatic primary
• Presence of residual ampullary adenoma or noninvasive papillary neoplasm is very useful
• CK20, MUC2, and CDX2 may be useful to distinguish from colonization by invasive pancreatic ductal adenoCA simulating a primary ampullary adenoma

Immunophenotype:

Marker:	Sensitivity:	Specificity:
CK20	Most intestinal-type Neg in most pancreatobiliary type
CK7	~1/2 intestinal type Most pancreatobiliary type
CDX2	Intestinal type Neg in pancreatobiliary type
MUC2	Intestinal type Neg in pancreatobiliary type
MUC1	Pancreatobiliary type
CEA	Most (both types)
CA19-9	Most (both types)
SMAD4 (DPC4)	No expression in ~35%

Molecular features:

Other features:

References:

• Bosman FT, Carneiro F, Hruban RH, Theise ND (eds.) WHO Classification of Tumours of the Digestive System (2010)
• Some notes taken from histology, IHC, and DDx