Rodger C. Haggitt Slide Seminar: Lesions of Esophagus, Stomach, and Duodenum
Moderators: Dr. Cecilia Fenoglio-Preiser and Dr. Wendy Frankel
Case 2 -
Adenomyoma of the ampulla of Vater
Drs. Jean-François FLEJOU, Adriana HANDRA-LUCA
Service d'Anatomie Pathologique, hôpital Saint-Antoine
Assistance Publique-Hôpitaux de Paris
Université Pierre et Marie Curie
48 yrs old woman. No remarkable past medical history. For 5 years, several attacks of right upper
abdominal pain with transient and mild increase in gamma-glutamyltransferase. Normal abdominal US and CT
scan, with normal intra- and extrahepatic biliary tract. On repeated upper digestive endoscopies,
polypoid lesion of the major papilla, increasing in size on the last examination (from 15 to 20 mm). Two
series of biopsies show reactive and inflammatory changes, with no evidence of neoplasia. On
echoendoscopy, the nodule measures 26mm in its greater dimension and is limited to the ampulla of Vater.
Due to strong clinical suspicion of an ampulloma, duodenopancreatectomy is performed.
The slide that is submitted is from the major papilla.
Case 2 - Slide 1
On macroscopy, the surgical specimen shows a nodular polypoid lesion (30 x 20 mm) of the major
papilla, covered by a normal duodenal mucosa. There is a moderate dilatation of the Wirsung duct and
common bile duct. The head of the pancreas is macroscopically normal.
The entire lesion of the papilla and ampulla of Vater was sampled for histological examination, and
the lesions were similar on all slides, including the slide that was submitted in the seminar.
The lesion consists of multiple lobules of glands, mainly located in the muscle layers of the Vaterian
system and major papilla. The abnormally located glands are covered by a single-layer epithelium that
shows no atypia and no mitotic figures. The lobular formations consist of small glands sometimes
disposed around a larger gland and surrounded by a myofibroblastic and fibroblastic proliferation. There
are also mild non specific inflammatory changes. The duodenal wall and the pancreas are normal at
distance from the papilla.
Diagnosis: Adenomyoma of the Ampulla of Vater
Adenomyoma is a rare benign lesion of the hepatobiliary and gastrointestinal tract, with most cases
described in the gallbladder. A few cases have been reported elsewhere in the gastrointestinal tract,
including the stomach, small bowel, bile ducts and the ampullary region. Adenomyoma of the Vaterian
system is an exceptional benign lesion. In the WHO classification it is defined as a tumor-like lesion
of extrahepatic bile ducts
The neoplastic or malformative origin of this lesion is still subject to controversy.
Despite its benign nature, adenomyoma is responsible for biliary obstruction and can be misdiagnosed
as carcinoma or adenoma. Therefore it is treated frequently by extensive surgery. We have reported
recently a series of 13 cases, with detailed histological and immunohistochemical features .
The diagnosis of adenomyoma was made in our series and in most single case reports on histological
examination of surgically resected specimens. On macroscopic examination, the ampulla of Vater and/or
the terminal portion of the common bile duct exhibit a firm, grossly nodular lesion measuring 10 to 30 mm
in diameter, that extend to the major papilla in most cases.
The overlying mucosa is normal, without ulceration. In some of our cases there were associated
pancreatic abnormalities: annular pancreas in one case and pancreas divisum in 2 cases.
The histological aspect of adenomyoma is characterized by multiple lobules of glands, mainly located
in the muscle layers of the Vaterian system resulting in a hypertrophy of the sphincter of Oddi (which
also explains the stenosis of the terminal common bile duct). Involvement of the major papilla can be
present. The abnormally located glands are covered by a single-layer epithelium that shows no atypia and
no mitotic figures and are surrounded by a myofibroblastic and fibroblastic proliferation. This
component may contain also sparse capillaries, inflammatory cells, and muscle fibers. Nonspecific
inflammatory changes may be present, and they could be secondary to sphincterotomy or migration of
Pancreatic heterotopia of the duodenal wall is present in some cases, with transition zones between
heterotopic tissue and adenomyoma showing progressive loss of acinar structures and endocrine islets and
an increase of ductular-glandular structures.
Proliferative activity, as estimated by immunohistochemical staining with Ki67 antibody, is absent in
the myofibroblastic component of the lesion, and very low in the epithelial component, similar to that
observed in the normal pancreatic ducts. Glandular epithelial cells, similarly to the normal epithelial
cells of the pancreatic and biliary duct system, express cytokeratin 7, and do not express cytokeratin
20. The myofibroblastic phenotype of most spindle cells is confirmed by a strong cytoplasmic expression
of smooth muscle actin.
Clinical and imaging features
In our series of 13 cases, adenomyoma was diagnosed only in adult patients (mean age: 63 years,
range: 38-78 years), with no male or female predominance. Clinical
complaints initially suggested long term biliary tract obstruction, and relapsed after sphincterotomy.
In 3 cases several episodes of increase of serum aminotransferase level were noted. In 3 cases the
lesion was discovered incidentally in patients presenting unrelated conditions.
Preoperative imaging procedures suggested a diagnosis of Vaterian system tumor. Most lesions were of
small size, with a benign or malignant nature that was not established before surgery. On endoscopy, the
major papilla showed a nodular pattern without ulceration. Endosonography showed intra-ampullary
heterogenous lesions (measuring between 10 and 21 mm) stenosing the terminal part of the common bile
duct. The proximal common bile duct and/or the pancreatic duct were dilated in most cases with bicanalar
dilation in 4 cases.
Endoscopic papilla biopsies (performed in 9/13 cases) showed epithelial cell atypias that were
considered as highly suggestive for dysplasia in 6 of the cases. This was interpreted retrospectively as
rather secondary to a regenerative post-sphincterotomy process and/or to the reactive changes related to
migration of gallstones.
Treatment and evolution
In our series of 13 cases, pancreaticoduodenectomy was performed in all cases, due to either severe
and/or recurrent symptoms after sphincterotomy. On follow-up (1 to 73 months), there was no evidence of
recurrence in any of the patients.
There is no established treatment for Vaterian system adenomyoma in the literature. Endoscopic
sphincterotomy should be required in order to restore adequate biliary drainage. When a surgical
treatment is decided, intra-operative frozen section could be of help leading to a limited resection
instead of extensive surgery like pancreaticoduodenectomy. Some authors suggest a careful follow-up in
such cases, with repeated endoscopic retrograde cholangiographies to ensure the benign diagnosis. It
appears retroscpectively that in our series, ampullectomy could have been the treatment in eight cases.
The histogenesis of adenomyoma is still a subject of controversy. The most widely accepted
hypothesis is that adenomyoma represents a form of incomplete heterotopic pancreas. The presence of
hyperplastic smooth muscle tissue can be explained by secondary muscle proliferation due to some stimulus
emanating from misplaced epithelium, or by muscle misarrangement, or by an aberrant growth invading and
distorting normal muscle. The possibility of a complex form of heterotopia, of enteropancreatic type,
could explain the presence within the same lesion of different glandular epithelial patterns such as
Brunner's glands and intestinal glands. However, pancreatic heterotopic tissue was present in only 3 of
Vaterian system adenomyoma is a rare lesion of clinical importance. In the majority of cases,
although it is an entirely benign lesion, this is because of its clinical and endosonographic
similarities with ampullary tumors like adenoma, or carcinoma. The clinicopathological features of
ampullary adenomyoma are consistent with a heterotopic nature, but other mechanisms (hyperplasia of
intramural glands of the common bile duct, reactive changes due to the inflammatory response to migration
of gallstones) are probably involved in the genesis of this lesion.
Immunohistochemical criteria like cytokeratin 7 expression and a low proliferative index (Ki67) in the
epithelial cells (without cytokeratin 20 expression) should be considered in the analysis of ampullary
biopsy specimens in order to differentiate adenomyoma from adenomatous or carcinomatous ampullary tumors,
and thus considered as well in the decision to perform a limited surgical resection.
- Albores-Saavedra J, Henson DE, Sobin LH. Histological typing of tumors of the gallbladder and extrahepatic bile duct. World Health Organization. Berlin, Springer-Verlag, 1991.
- Albores-Saavedra J, Henson DE. Tumors of the gallbladder and extrahepatic bile duct. In: Atlas of tumor pathology, Second Series. Armed Forces Institute of Pathology, Washington, 1986.
- Handra-Luca A, Terris B, Couvelard A, Bonte H, Flejou J-F. Adenomyoma and adenomyomatous hyperplasia of the Vaterian system: clinical, pathological, and new immunohistochemical features of 13 cases. Mod Pathol 2003;16:530-536.