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Ampulla of Vater

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Revised: 26 December 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Benign/non-neoplastic

Normal anatomy


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 27 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Ampulla means flask like dilatation (spreading or stretching) of a tubular structure
● May refer to Ampulla of Vater, or portion of fallopian tube, vas deferens, semicircular canal or colon
● Vater (“fah-ter”) is German anatomist Abraham Vater (1684-1751) who first described this structure
● Usually refers to confluence of distal common bile duct and main pancreatic duct in second portion of duodenum near pancreatic head, although in 42% of patients, ampulla is termination of common bile duct only as the pancreatic duct enters the duodenum separately next to ampulla; in these cases, ampulla may be difficult to locate or nonexistent
● Ampulla is 1.5 cm long or less, traverses duodenal wall, opens into the duodenal lumen through (major) duodenal papilla (papilla of Vater), a 0.5 cm in diameter mucosal elevation with mucosal reduplications (valves of Santorini) that probably prevent regurgitation
● Minor papilla, also called accessory pancreatic duct (APD) of Santorini, is 2 cm proximal and slightly anterior to major papilla
● APD is Patent in 50% cases, pancreatic tissue is noted in 80% of cases in minor papilla (Dig Surg 2010;27:137)
● Ampulla is surrounded by muscular fibers of sphincter of Oddi

Gross images
=========================================================================


Figure 1 a and b

Micro images
=========================================================================


Figure 1 and 2

Drawings
=========================================================================



Local anatomy (called common duct)


Papilla

Additional references
=========================================================================

Dig Surg 2010;27:90



Benign/non-neoplastic

Normal histology


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 30 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Mucosa forms prominent papillary folds / reduplications resembling fallopian tubal fimbriae with fibrovascular cores
● Lined by pancreaticobiliary-type ductal epithelium with occasional goblet cells, no absorptive-type cells
● Lamina propria has only occasional lymphocytes, plasma cells and mast cells
● May have adjacent pancreatic acini, but usually no islets around major papillae
● Common bile duct can be distinguished from main pancreatic (Wirsung) duct by its larger size, more prominent folds, thicker musculature, intraluminal bile
● Ampullary biopsy performed in autoimmune pancreatitis can help to differentiate from other “mass forming” pancreatitis by IgG4+ to IgG+ ratio (Am J Surg Pathol 2008;32:1770)



Benign/non-neoplastic

Adenomyoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 26 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called adenomyomatous hyperplasia
● Rare, benign
● Usually stomach, duodenum, jejunum
● Often causes pain in right upper quadrant, radiating to back
● May cause biliary obstruction and common bile duct dilation (Arch Pathol Lab Med 1987;111:388)

Case reports
=========================================================================

● 55 year old woman with history of duodenal ulcers (Arch Pathol Lab Med 2001;125:701)
● 74 year old woman presenting as acute recurrent pancreatitis (World J Gastroenterol 2007;13:2892)

Treatment
=========================================================================

● Excision

Gross description
=========================================================================

● Mass at head of pancreas, usually 0.5 cm or more

Gross images
=========================================================================



Top: pedunculated polypoid tumor (2 cm) in lower bile duc, common bile duct showed marked dilatation; Bottom: tumor localized in bile duct, but no infiltration into surrounding tissue


Top: common bile duct shows marked dilatation, but no apparent tumor; Bottom: small ill-defined nodular lesion of adenomyomatous hyperplasia

Micro description
=========================================================================

● Well circumscribed, nodular proliferation of smooth muscle cells, ducts and glands, clearly disorganized compared to normal
● Ducts and glands are lined by columnar/cuboidal cells
● No atypia, no mitoses, usually no pancreatic tissue

Micro images
=========================================================================



Benign ducts with whorled smooth muscle stroma


a-proliferation of epithelial glandular cells and stromal myofibroblastic spindle cells without atypia; b-surface epithelial cells are MUC5AC+; c-most inner epithelial cells are MUC6+; d-few inner pithelial cells are focally CA/HIK1083+


a-proliferation of epithelial glandular cells and stromal myofibroblastic spindle cells without atypia; b-inner epithelial cells in the inner area rarely expressed MUC5AC; c-most inner epithelial cells in the inner area expressed MUC6; d-a few inner epithelial cells expressed CA/HIK1083

Positive stains
=========================================================================

● MUC6, focal surface positivity for MUC5AC (J Hepatobiliary Pancreat Sci 2010;17:275)

Negative stains
=========================================================================

● MUC1, MUC4

Differential diagnosis
=========================================================================

● Normal intraampullary common bile duct (normally has dense muscular layer)
● Ectopic pancreatic tissue
● Fibroadenoma
● Brunner gland hyperplasia



Benign/non-neoplastic

Fibrosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 21 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Signs/symptoms of right sided upper abdominal pain and pinpoint ampullary opening
● Associated with chronic gallbladder or pancreatic disease



Benign/non-neoplastic

Gangliocytic paraganglioma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 27 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare tumor of periampullary region and second part of duodenum
● Usually benign, rarely has local metastases of endocrine component but even these cases are indolent
● May recur if incompletely excised
● May derive from endodermal-neuroectodermal complexes in the embryonic ventral pancreas
● Presents with GI bleeding or incidental finding

Case reports
=========================================================================

● 43 year old man (Arch Pathol Lab Med 2002;126:1239)
● 56 year old man (World J Surg Oncol 2010;8:42)

Clinical images
=========================================================================



Periampullary submucosal tumor and surface ulcer bleeding.

Gross description
=========================================================================

● Usually 1-3 cm, sessile or polypoid, no capsule

Micro description
=========================================================================

● Unencapsulated submucosal lesion
● Triphasic, with epithelioid, spindle cell (Schwann cell like), and ganglion type cells of varying proportions resembling carcinoid tumor (endocrine type cells in compact nests and trabeculae), paraganglioma and ganglioneuroma
● Usually infiltrative pattern
● Variable stromal amyloid

Micro images
=========================================================================



Various images


Ganglion-like (fig 3), spindle (fig 4A) & epithelial cells (fig 4B)

Positive stains
=========================================================================

Endocrine cells - pancreatic polypeptide, somatostatin
Ganglion cells - chromogranin, synaptophysin, neuron specific enolase, somatostatin
Spindle cells - S100

Electron microscopy description
=========================================================================

● Dense core granules

Differential diagnosis
=========================================================================

● Ganglioneuroma
● Paraganglioma
● Carcinoid
● Carcinoma

Additional references
=========================================================================

In Vivo 2010;24:321, Arch Pathol Lab Med 2001;125:1098 (nasopharyngeal tumor)



Benign/non-neoplastic

Granular cell tumor


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 44 year old man (J Postgrad Med 2005;51:36)

Micro images
=========================================================================



Abundant granular cytoplasm and bland nuclei



Benign/non-neoplastic

Pancreatic heterotopia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 30 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Very common
● May cause obstructive jaundice



Benign/non-neoplastic

Hyperplastic polyp


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Similar to serrated polyps in colorectum (Hum Pathol 2011;42:1953)
● Rare, occur in second part of duodenum and ampulla
● Usually incidentally detected, mean age 50 yrs
● Uncertain malignant potential

Positive stains
=========================================================================

● MUC6 expression in crypt bases



Benign/non-neoplastic

Papillary hyperplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 27 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Poorly defined concept - no clinical significance

Micro description
=========================================================================

● More prominent papillary folds than usual, no dysplasia

Differential diagnosis
=========================================================================

● Adenoma (dysplastic epithelium)



Premalignant / noninvasive

Adenoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Similar histologically to colonic adenoma
● Increased incidence in familial adenomatous polyposis syndrome
● Excellent prognosis if completely excised

Treatment
=========================================================================

● Polypectomy or pancreatoduodenectomy since premalignant

Micro description
=========================================================================

● Tubular, villous or mixed, similar to adenomas in colon, although:
(a) Dysplastic epithelium may have only subtle changes of mild cellular stratification and fine chromatin pattern
(b) Often contain prominent Paneth cells (with coarse, large, red-pink, refractile granules in supranuclear cytoplasm), endocrine cells (dark, red-purple, fine small granules in basal cytoplasm) and goblet cells
● Associated with high grade PanIN in 40% of cases, similar rate as adenocarcinomas

Micro images
=========================================================================



Tubular adenoma with mild dysplasia


Villous adenoma


Intestinal type adenoma

Cytology description
=========================================================================

● Endoscopic brush cytology is sensitive and specific for adenoma /carcinoma, although diagnosis of adenoma does not exclude coexisting carcinoma (Am J Clin Pathol 1998;109:540)

Molecular description
=========================================================================

● Sporadic and FAP-related adenoma show similar molecular features to colorectal adenoma, with presence of APC and KRAS mutations
● BRAF mutations, p53 alterations, and DNA mismatch repair abnormalities are rare (Am J Surg Pathol 2008;32:1388)

Differential diagnosis
=========================================================================

IPMN of pancreas or common bile duct adenoma extending into ampulla

Additional references
=========================================================================

Am J Clin Pathol 2009;132:506



Premalignant / noninvasive

Intra-ampullary papillary-tubular neoplasm (IAPN)


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● First described in 2010 (Am J Surg Pathol 2010;34:1731)
● Highly analogous to pancreatic or biliary intraductal tubulopapillary neoplasm, with variable cell lineage, and spectrum of dysplastic change (adenoma-carcinoma sequence)
● Biologically indolent
● Noninvasive examples have excellent prognosis, invasive tumors have better prognosis than other ampullary malignancies
● 28% of ampillary carcinomas arise in association with IAPNs

Micro images
=========================================================================





Various images



Premalignant / noninvasive

Intraductal papillary mucinous neoplasm (IPMN)


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 30 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Analogous to tumor of pancreas
● Often associated with invasive carcinoma (so examine thoroughly)
● May recur and progress



Carcinoma

Adenocarcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● By definition, centered in ampulla of Vater, arises from ampullary intestinal mucosa
● If advanced, cannot distinguish tumor origin between ampulla, distal common bile duct or pancreas

Etiology
=========================================================================

● May arise from villous adenoma or villoglandular polyp; usually is a co-existing adenoma
● Carcinomas of pancreas, gallbladder, extrahepatic bile ducts and ampulla have common embryonic cellular ancestry, differentiation pathways, mucosal histologic patterns and population-related tumor development, indicating a field effect in carcinogenesis
● Carcinomas of pancreas are more common than at these other sites because pancreatic ductal system has a greater surface area (Arch Pathol Lab Med 2009;133:67)

Sites
=========================================================================

● May arise within ampulla (intra-ampullary) or in periampullary duodenum without significant ampullary involvement
● Site of origin may be difficult to determine

Clinical features
=========================================================================

● 5% of GI malignancies are ampullary or periampullary adenocarcinoma
● 80% of ampullary neoplasms and 90% of ampullary malignancies are adenocarcinomas
● Peak age in 70’s, men affected more than women
● 1/3 have other malignancies
● May be associated with multiple polyposis syndrome and neurofibromatosis
● Causes jaundice, abdominal pain, occasionally pancreatitis
● Nodal metastases at diagnosis in 35% (usually adjacent periampullary nodes)
● Immunohistochemically detected lymph node micrometastasis indicates intensive lymphatic spread, and adversely affects the survival of patients with ampullary carcinoma (World J Surg 2006;30:985)
● Metastasizes to liver, lung, peritoneum, pleura
● On CT scan, a small intra-ampullary tumor may show dilated ducts without a mass; ultrasound may be better imaging modality

Prognostic factors and survival
=========================================================================

● 5 year survival after resection is 40-50%, 80% if no nodal metastases - better than pancreatic or bile duct carcinoma (10-20%)
Poor prognostic factors: high stage (J Surg Oncol 2012;105:266), tumor size 2.5 cm or more, signet-ring, poorly differentiated or non-papillary histology, perineural invasion, angiolymphatic invasion, ulceration, invasion of muscle of sphincter of Oddi, invasion into pancreatic parenchyma, nodal metastases, positive margins, tumor budding (Am J Surg Pathol 2010;34:1417)
● Also total bilirubin greater than 5 mg/dl (Scand J Surg 2011;100:92), Ki-67 / mitotic activity index (MI) (World J Surg 2010;34:2115)
● Possibly osteopontin-positive infiltrating tumor-associated macrophages (Cancer Biol Ther 2010;10:144)
Good prognostic factors: papillary histology, intestinal type (Hepatogastroenterology 2007;54:1641), carcinomas arising in adenomas (J Surg Oncol 2009;100:598), promyelocytic leukemia gene expression (Ann Oncol 2009;20:78), Bax expression (J Clin Pathol 2005;58:159)

Case reports
=========================================================================

● 41 year old woman with adenocarcinoma arising in ampullary villous adenoma with synchronous malignant duodenal GIST (J Clin Pathol 2004;57:1118)
● 54 year old woman with neurofibromatosis type 1 (Mod Pathol 2001;14:1169)
● 56 year old and 67 year old women with signet-ring cell carcinoma (Ann Clin Lab Sci 2004;34:471, JOP 2004;5;495)
● 72 year old man with double malignancy of colon and ampulla (Saudi J Gastroenterol 2012;18:143)
● Presentation as recurrent pancreatitis (Acta Gastroenterol Belg 2004;67:309)

Treatment
=========================================================================

● Whipple procedure

Gross description
=========================================================================

● Tumor bulges into duodenal lumen, may be intra-, peri-ampullary or mixed
● Often small
● Common bile duct often dilated

Gross images
=========================================================================



Mass with central ulceration


Contributed by Dr. Semir Vranic, University of Sarajevo, Bosnia and Herzegovina

Micro description
=========================================================================

● Usually poorly differentiated, may have papillary component resembling villous adenoma or villoglandular polyp
● Intestinal (arising from covering intestinal mucosa of papilla, large elongated tubules) or pancreaticobiliary (arise from ductal epithelium that penetrates duodenal muscularis propria, smaller glands/tubules with desmoplastic stroma)
● 50% have vascular invasion, occasional perineural invasion
● Non-invasive papillary lesions resemble colorectal villous adenoma; may be associated with familial colonic polyposis with a high risk for malignant transformation
● Differentiation is based on % glands (well: >95%, moderate: 50-95%, poor: 5-49%, undifferentiated: <5%)
● Lamina propria invasion is considered by some as invasion due to rich lymphatics (Am J Surg Pathol 1991;15:1188)
● Also PanIN (1/3, Mod Pathol 2001;14:139), pancreatitis (1/3)
Variants: colloid, hepatoid, medullary, micropapillary, mixed acinar-endocrine, mucinous, neuroendocrine, Paneth cell, signet ring cell

Micro images
=========================================================================



Intestinal, pancreaticobiliary and other subtypes

 
Various images


Early tumor


Advanced tumor


Budding




Line 1: H&E; Line 2: CEA, CK7, CK20, MSH2
Contributed by Dr. Semir Vranic, University of Sarajevo, Bosnia and Herzegovina



Potential diagnostic pitfalls


CDX2 staining: various images


DPC4 staining in invasive carcinoma and adenomas with high grade dysplasia

Positive stains
=========================================================================

Intestinal and pancreaticobiliary types: CD24, P-cadherin, S100 A4 (Mod Pathol 2009;22:306)
Intestinal type: MUC2+, CDX2+ (Mod Pathol 2004;17:1392), MUC1-, MUC5AC-, CD17-; also CK7-, CK20-
Pancreaticobiliary type: MUC1+, MUC5AC+, CK17+ (Am J Surg Pathol 2005;29:359), MUC2-, CDX2-; also CK7+, CK20- (Am J Surg Pathol 2004;28:875)
Mucinous type: frequently CK7+ and MUC6+ (Am J Surg Pathol 2011;35:1830)
● Also COX2 (J Clin Pathol 2006;59:492), mesothelin (Am J Clin Pathol 2005;124:838), p53 (>50%)

Negative stains
=========================================================================

● Loss of DPC4 in 34%
● Reduced expression of Raf-1 kinase inhibitory protein (Virchows Arch 2012;460:61)

Molecular description
=========================================================================

● K-ras activating point mutations in 40% (Am J Clin Pathol 2011;135:202)
● Microsatellite instability develops early in adenomatous stage and is reliably detectable in the precursor lesion
● Mismatch repair deficient molecular pathway of ampullary and colonic carcinomas are similar (Am J Surg Pathol 2009;33:691)


Kras mutations: Am J Clin Pathol 2011;135:202

Differential diagnosis
=========================================================================

● Adenomatous changes in submucosal glands / ductules simulating invasion, cautery artifact, reactive epithelial atypia (Am J Clin Pathol 2009;132:506)
● Common bile duct carcinoma: thickening of common bile duct, granular mucosa, usually well differentiated adenocarcinoma formed by small glands with marked desmoplasia
● Duodenal adenocarcinoma-not ampullary: may also arise in villous adenoma

Additional references
=========================================================================

eMedicine, Diagn Pathol 2011;6:102



Carcinoma

Adenosquamous carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 1 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare in ampulla

Case reports
=========================================================================

● 76 year old man (Korean J Gastroenterol 2006;48:132)



Carcinoma

Colloid carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 1 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually associated with intraductal papillary mucinous neoplasm or tubular/tubulovillous adenoma (Am J Surg Pathol 2002;26:56)
● Similar prognosis to other periampullary adenocarcinomas (in above study)

Micro description
=========================================================================

● Predominantly mucin lakes with floating malignant epithelial cells and minimal conventional adenocarcinoma
● May contain signet ring cells

Micro images
=========================================================================



Colloid carcinoma



Carcinoma

Hepatoid adenocarcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare
● Similar tumors found in lung, ovary, stomach
● Produce alpha-fetoprotein in blood

Micro description
=========================================================================

● Tubular, papillary, trabecular
● Hepatoid-like with PAS positive hyaline globules

Positive stains
=========================================================================

● AFP, CEA

Additional references
=========================================================================

Histopathology 1992;20:541, Zhonghua Bing Li Xue Za Zhi 2009;38:494



Other malignancies

Metastases


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Uncommon

Case reports
=========================================================================

● Vaginal melanoma metastases (Intern Med 2011;50:345)



Carcinoma

Mixed acinar-endocrine carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● May arise in heterotopic pancreatic cells
● Acinar cell carcinoma component is composed of pancreatic acinar cells with zymogen granules on EM

Case reports
=========================================================================

● 47 year old man with neurofibromatosis-1, ampullary somatostatinomas and jejunal gastrointestinal stromal tumor (World J Gastroenterol 2007;13:2761)
● 49 year old woman with neurofibromatosis-1 and mixed endocrine somatostatinoma (JOP 2010;11:64)
● 78 year old man (Hum Pathol 2002;33:449)

Micro description
=========================================================================

● Nests of tumor cells with acinar structures and endocrine immunoreactivity and endocrine granules on EM

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Amylase, trypsin, synaptophysin

Electron microscopy description
=========================================================================

● Endocrine and zymogen granules



Carcinoma

Neuroendocrine carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare, present with progressing jaundice
● Aggressive with poor prognosis (Hepatobiliary Pancreat Dis Int 2008;7:422)

Case reports
=========================================================================

● 55 year old woman with large cell neuroendocrine carcinoma with glandular differentiation (J Clin Pathol 2004;57:1098)
● 73 year old woman with large cell neuroendocrine carcinoma with squamous cell and glandular components (Jpn J Clin Oncol 2011;41:434)
● 74 year old man with small cell neuroendocrine carcinoma with villous adenoma (World J Gastroenterol 2008;14:4709)
● 74 year old with large cell neuroendocrine carcinoma (Arch Pathol Lab Med 2003;127:221)

Micro description
=========================================================================

Large cell tumor -
● Islands and trabeculae of large cells with brisk mitotic activity and extensive necrosis
● Cells have more cytoplasm than small cell carcinoma, irregular chromatin, frequent nucleoli

Micro images
=========================================================================



Large cell neuroendocrine carcinoma


Small cell neuroendocrine carcinoma

Positive stains
=========================================================================

Large cell tumor - cytokeratin, chromogranin, synaptophysin, neuron-specific enolase

Differential diagnosis
=========================================================================

● Carcinoid
● Small cell carcinoma
● Lymphoma
● Poorly differentiated carcinoma
● Metastases



Carcinoma

Neuroendocrine tumors - staging


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Primary tumor (T)
=========================================================================

TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Tumor invades lamina propria or submucosa and tumor size 1 cm or less
T2: Tumor invades muscularis propria or tumor size >1 cm
T3: Tumor invades through the muscularis propria into pancreas or retroperitoneum (ampullary or duodenal tumors) or into nonperitonealized tissues
T4: Tumor invades visceral peritoneum (serosa) or invades other organs

● For any T, add (m) for multiple tumors

Regional lymph nodes (N)
=========================================================================

NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastasis

Distant Metastasis (M)
=========================================================================

M0: No distant metastasis
M1: Distant metastasis

Anatomic stage / prognostic groups
=========================================================================

Stage I: T1 N0 M0
Stage IIA: T2 N0 M0
Stage IIB: T3 N0 M0
Stage IIIA: T4 N0 M0
Stage IIIB: Any T N1 M0
Stage IV: M1 (any T, any N)

Additional references
=========================================================================

Virchows Arch 2006;449:395, Staging form



Carcinoma

Paneth cell carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare
● Excluding neoplasms, paneth cells usually are limited to lining epithelium of small intestine, appendix and proximal colon

Case reports
=========================================================================

● 64 year old man with virtually all neoplastic cells resembling Paneth cells (Arch Pathol Lab Med 2004;128:908)

Micro images
=========================================================================



Various images

Positive stains (granules)
=========================================================================

● Lysozyme, PAS (weak)



Carcinoma

Signet ring cell carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 59 year old man (JOP 2009;10:690)
● Primary signet-ring cell carcinoma (Appl Immunohistochem Mol Morphol 2012;20:427)

Micro images
=========================================================================



Tumor cells contain abundant intracytoplasmic mucin with nuclei located on one side



Other malignancies

Adenocarcinoid


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 29 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Prognosis intermediate between carcinoids and adenocarcinoma (Hum Pathol 1989;20:198)

Case reports
=========================================================================

● 67 year old female with mixed carcinoid with adenocarcinoma (World J Gastroenterol 2009;15:4199)

Micro images
=========================================================================



H&E, Chromogranin A



Other malignancies

Carcinoid


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 1 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● 3% of ampullary tumors
● Patients typically present with jaundice
● Compared to duodenal carcinoids (which are usually benign), are more aggressive with shorter survival (may die within 1 year), have more metastases
● Somatostatin producing tumors are common, have a glandular pattern, are associated with psammoma bodies and neurofibromatosis, have 50-70% nodal metastases (Am J Clin Pathol 1991;95:51, Am J Clin Pathol 1983;80:755, Am J Clin Pathol 1992;97:411, Am J Surg Pathol 1989;13:828)

Case reports
=========================================================================

● 52 year old Chinese woman with inflammatory pseudotumor associated with periampullary carcinoid (Singapore Med J 2009;50:e100)

Micro description
=========================================================================

● Classic features of carcinoid tumors; somatostatin producing tumors are often mucin+

Micro images
=========================================================================



Monotonous tumor cells with small round nuclei plus various images

Positive stains
=========================================================================

● Chromogranin (60%), synaptophysin (60%), gastrin (20% vs. 75% of duodenal carcinoids, Hum Pathol 2001;32:1252)
● Also somatostatin and pancreatic polypeptide

Differential diagnosis
=========================================================================

● Adenocarcinoma

Additional references
=========================================================================

Arch Pathol Lab Med 2010;134:181-CAP protocol for examination of carcinoid tumors



Other malignancies

GIST


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● Unresectable primary GIST of the ampulla of Vater (Korean J Gastroenterol 2010;56:39)



Other malignancies

Lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● High incidence of follicular lymphoma in duodenum, usually periampullary
● May mimic pancreatic adenocarcinoma
● Associated with multiple small polyps
● Indolent behavior (Am J Surg Pathol 2000;24:688)

Case reports
=========================================================================

● 36 year old woman with diffuse large B cell lymphoma (J Gastrointest Cancer 2012;43:340)
● 43 year old man with combination follicular lymphoma of ampulla of Vater and endocrine tumor of common bile duct (World J Surg Oncol 2011;9:4)
● 56 year old woman with follicular lymphoma presenting as obstructive mass (Am J Surg Pathol 1997;21:484)

Micro images
=========================================================================



Follicular lymphoma



Other malignancies

Pancreatoblastoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 78 year old woman with ampullary pancreatoblastoma (Arch Pathol Lab Med 2003;127:1501)

Gross images
=========================================================================



Pancreaticoduodenectomy specimen

Micro images
=========================================================================



Various images



Miscellaneous

Grossing ampullary tumors


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 27 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● Ink pancreatic duct and common bile duct margins, also retroperitoneal margin
● Probe common bile duct and pancreatic duct, and section along plane of both probes
● Should examine at least 12 lymph nodes in a pancreaticoduodenectomy specimen



Miscellaneous

Frozen section


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● Major criteria for malignancy are nuclear size variation of at least 4:1 between ductal epithelial cells, incomplete ductal lumens, disorganized duct distribution
● Minor criteria are huge, irregular epithelial nucleoli, necrotic glandular debris, glandular mitoses, glands unaccompanied by connective tissue stroma within smooth muscle bundles, perineural invasion (Am J Surg Pathol 1981;5:179)



Miscellaneous

TNM staging


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● No change from AJCC 6th to AJCC 7th edition
● Does not apply to carcinoid or other neuroendocrine tumors

Primary tumor (T)
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TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor limited to ampulla of Vater or sphincter of Oddi
T2: Tumor invades duodenal wall
T3: Tumor invades pancreas
T4: Tumor invades peripancreatic soft tissues or other adjacent organs or structures

Regional lymph nodes (N)
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NX: Regional lymph node status cannot be assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastasis

● Regional lymph nodes: peripancreatic, which includes lymph nodes along hepatic artery and portal vein
● Optimal histologic examination requires a minimum of 12 lymph nodes

Distant metastasis (M)
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M0: No distant metastasis
M1: Distant metastasis (specify site)

Extent of resection
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R0: Complete resection with gross/microscopically negative margins
R1: Grossly negative, microscopically positive
R2: Grossly and microscopically positive

● Note: not part of TNM but prognostically of great significance

Stage groupings
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Stage 0: Tis N0 M0
Stage 1A: T1 N0 M0
Stage 1B: T2 N0 M0
Stage 2A: T3 N0 M0
Stage 2B: T1-T3 N1 M0
Stage 3: T4, any N, M0
Stage 4: Any T, any N, M1



Miscellaneous

Features to report


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 1 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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Editor’s note

Items listed below are mandatory to report for accreditation purposes by American College of Surgeons Committee on Cancer, except those in italics, which are optional but still recommended

● Specimen type
● Tumor site
Presumed tumor origin (intraampullary, periampullary duodenum, mixed, common bile duct, pancreatic)
● Histologic type
● Histologic grade (well, moderate, poor or undifferentiated)
● Tumor size (invasive carcinoma component)
● Depth of invasion, local extension
● Margins - invasive carcinoma; distance to closest margin and identify margin (recommended to ink posterior retroperitoneal surface of pancreas and submit sections of tumor closest to this margin)
● Margins - carcinoma in situ; involvement of pancreatic duct or common bile duct margin
Margins - PanIn
● Pathologic staging
● Perineural invasion (for resections)
● Angiolymphatic invasion (for resections)
● Lymph nodes
Additional findings: PanIN / dysplasia, adenoma, inflammation, adenomyosis, pancreatitis, gastritis, other

End of Ampulla of Vater > Superpage


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