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 Paris, France

Clinical history 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 Click to view with ImageScope Click to view with a Web-Based Viewer Morphological lesions 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 Discussion 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 [1, 2]. 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 [3]. Morphological features Macroscopy 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. Histological features 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 gallstones. 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. Immunohistochemical features 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. Histogenesis 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 our cases. Conclusion 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. References 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.