—  SPECIALTY CONFERENCE  —

Gastrointestinal Pathology

Case 4 - Pyloric Gland Adenoma

Amy Noffsinger
University of Chicago Medical Center
Chicago, IL





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Clinical History:
The patient is an 80 year old woman with a history of hematemesis. Esophagogastroduodenoscopy demonstrated a polypoid mass arising in the gastric cardia that measured 10 cm in greatest dimension. The remainder of the stomach appeared atrophic endoscopically. The esophagus and duodenum appeared normal. The polypoid lesion was removed endoscopically in a piecemeal fashion.


Case 4 - Figure 1
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Case 4 - Figure 4
Case 4 - Figure 5


Pathologic Features:
The specimen consisted grossly of a total of twelve fragments of pink-tan and red papillary friable tissue ranging in size from 1.0 to 4.0 cm in greatest dimension. Histologically, the lesion appeared lobulated, and demonstrated foci of erosion which were presumed to represent the sites of bleeding. The polyp was comprised of closely packed glands lined by a simple columnar epithelium. In most areas, these epithelial cells had abundant eosinophilic to amphophilic cytoplasm and round, uniform nuclei aligned along the basement membrane. The nuclear chromatin was open, and most nuclei contained a prominent nucleolus. In occasional foci, the nuclei appeared somewhat more elongated, crowded and stratified. Mitotic figures were readily seen throughout the lesion. No distinct cytoplasmic mucin droplets were identifiable. The lamina propria surrounding the glands was somewhat edematous, but otherwise unremarkable. The adjacent gastric mucosa showed evidence of atrophic fundic gastritis with patchy intestinal metaplasia.

Differential Diagnosis:
The differential diagnosis in this case includes all gastric epithelial polyps:
  • Fundic gland polyp

  • Hyperplastic polyp

  • Juvenile polyp

  • Cronkhite-Canada polyp

  • Peutz-Jeghers polyp

  • Isolated hamartomatous polyp

  • Gastric adenoma
    • Intestinal type adenoma

    • Gastric foveolar type adenoma

    • Pyloric gland adenoma

Diagnosis:
Pyloric gland adenoma

Pyloric Gland Adenoma - Discussion
Pyloric gland adenoma is a relatively rare lesion that most commonly arises in the stomach [1, 2]. In one study, 85% of pyloric gland adenomas arose in this site, and overall comprised 2.7% of all gastric polyps (excluding fundic gland polyps) [1]. There are, however, few reported cases in the literature, suggesting that this lesion is likely underrecognized by pathologists. Approximately 15% of pyloric gland adenomas also occur in extragastric sites including the gallbladder, pancreatic ductal system, uterine cervix and in Barrett's esophagus and heterotopic gastric tissues in the duodenum and rectum [1, 2, 3, 4, 5, 6, 7, 8, 9, 10].

Gastric pyloric gland adenomas tend to arise in the elderly (average age at diagnosis is 73 years), and are more common in women than in men [1, 2]. Most arise in the body of the stomach, but they may also occur in the cardia or antrum [1, 2]. The surrounding gastric mucosa often shows evidence of autoimmune atrophic fundic gastritis or H. pylori gastritis [1, 2]. In only rare cases is the adjacent gastric mucosa normal.

Pyloric gland adenomas are often relatively large at the time of diagnosis. The mean diameter in one study was 16.1 + 9.1 mm [1]. Histologically, they are comprised of closely packed pyloric gland-type tubules or glands lined by a single layer of columnar or cuboidal epithelium. The cytoplasm is eosinophilic or amphophilic, and often has a "ground-glass" appearance. Mucin droplets are not identifiable in the cytoplasm. Nuclei are characteristically round, and may or may not contain easily identifiable nucleoli.

By immunohistochemistry, pyloric gland adenomas characteristically express MUC6 (a marker of pyloric gland mucin) and MUC5AC (a foveolar mucin marker) [2, 12]. The intestinal mucin MUC2 and the intestinal marker CDX2 are generally not expressed in pyloric gland adenomas [2, 13]. One study did demonstrate aberrant expression of CDX2 in a series of gallbladder pyloric gland adenomas [12].

Dysplasia is common in pyloric gland adenomas. In one study, 37% of cases showed no evidence of dysplasia, 12% showed low grade dysplastic changes, and 51% of cases demonstrated high grade dysplasia or invasive adenocarcinoma [2]. In the large series reported by Vieth [1], adenocarcinoma was identified in 30% of cases. These foci of carcinoma were generally small, and usually limited to the mucosa. Others have also reported a high frequency of associated gastric adenocarcinoma [11].

Little is known regarding prognosis in patients with pyloric gland adenoma since most studies have not reported follow-up data. Chen et al [2] had follow-up on 7 of their 36 patients. In three cases, deeply invasive carcinoma was identified subsequent to the diagnosis of pyloric gland adenoma (2 cases from the stomach and one from duodenum). All three patients were alive; the two with gastric lesions at 2 and 10 months post-op, and the third with recent recurrence of carcinoma 10 years after Whipple resection. Another two patients had residual dysplasia on follow-up, and one additional patient had no evidence of residual adenoma. In one patient without dysplasia, the lesion persisted, but remained histologically bland. Our patient has no evidence of residual or recurrent adenoma 9 months post endoscopic mucosal resection.

Differential Diagnosis
Pyloric gland adenomas are most easily mistaken for a strange form of gastric hyperplastic polyp. Like pyloric gland adenomas, hyperplastic polyps often arise in a background of atrophic gastritis. It is believed that hyperplastic represent an exuberant regenerative response of gastric foveolar cells. The gastric glands themselves do not usually participate in the formation of this type of polyp. Two major features categorize hyperplastic polyps. The first is marked elongation, infolding, and branching of the gastric pits leading to a corkscrew or serrated appearance. Tall mucin-secreting foveolar cells line exaggerated, elongated, and distorted pits that extend from the surface deep into the stroma. Hypertrophic foveolar cells resembling goblet cells can be present. The pits also dilate to form variably sized and shaped cysts, which can be quite prominent. Glandular epithelium may be found in the deeper parts of the polyps. The glands are often antral in type, even when the polyps arise in the body or fundus. In contrast, pyloric gland adenomas, are not comprised of foveolar-type cells with prominent apical cytoplasmic mucin droplets, and characteristically display a cytoplasmic "ground-glass" appearance.

Foveolar type gastric adenomas may also be confused with pyloric gland adenomas, but these also are made up of cells resembling foveolar epithelium similar to that of hyperplastic polyps. The nuclei of the foveolar-type gastric adenomas, however, appear hyperchromatic and dysplastic [14]. These lesions usually arise in gastric mucosa which does not show evidence of atrophy or intestinal metaplasia. It is important to distinguish foveolar-type and pyloric gland adenomas because the latter likely have a higher risk for high grade dysplasia or invasive adenocarcinoma [2].

Fundic gland polyps are the most common type of gastric polyp encountered by pathologists since these lesions are frequently seen in patients on proton-pump inhibitor therapy. Fundic gland polyps are localized hyperplastic expansions of the deep glandular compartment of the oxyntic mucosa. The overlying pits appear shortened or absent. They contain cystically dilated, irregularly deformed oxyntic glands with or without glandular proliferations, increased smooth muscle in the lamina propria, and a lack of hyperplastic foveolar cells. Unlike pyloric gland adenomas which are made up of a single cell type, the glands of fundic gland polyps are lined by a mixture of parietal, chief, and mucous neck cells.

Intestinal type gastric adenomas resemble their counterparts in the colon. They often contain scattered goblet or Paneth cells, and like pyloric gland adenomas, arise in association with atrophic gastritis and intestinal metaplasia. Flat dysplasia is also frequently seen in the gastric mucosa surrounding intestinal-type gastric adenomas [14].

Hamartomatous polyps are usually not easily confused with pyloric gland adenomas. Isolated gastric hamartomatous polyps consist of a prominent submucosal mass of haphazardly arranged oxyntic glands in a framework of smooth muscle tissue and occasional focal accumulations of mature lymphoid tissue. The entire lesion is supported by normal lamina propria. The glands may appear normal or be cystically dilated. One also sees mucous cells resembling foveolar epithelium as well as rare antral or cardiac-type glands containing endocrine cells indigenous to the mucosal site. The lesions differ from those seen in Peutz-Jeghers syndrome, which are usually not submucosal lesions but more mucosally based with possible submucosal extensions. In gastric Peutz-Jeghers polyps, the epithelial component consists of foveolar and pyloric glandular cells. Like their counterparts in the colon, gastric Peutz-Jeghers polyps may lack the arborizing smooth muscle bundles typical of small intestinal lesions. When the smooth muscle bundles are absent, gastric Peutz-Jeghers polyps may resemble gastric hyperplastic polyps.

Gastric polyps develop in patients with Cronkhite-Canada syndrome. These polyps are broad-based sessile lesions that contain corkscrew-shaped glands lined by foveolar type epithelial cells. Smooth muscle fibers extend up into the mucosa. The polyps contain an expanded, edematous lamina propria and distended, cystic glands lined by flattened epithelium, variable edema, and chronic inflammation. Gastric polyps tend to occur in the antrum forming hyperplastic gastric folds, some of which mimic Menetrier disease.

Gastric juvenile polyps consist of hyperplastic foveolae and edematous stroma with inflammatory cells, and may also resembling gastric hyperplastic polyps. They also resemble the polyps seen in Cronkhite-Canada syndrome. A definitive diagnosis requires knowledge of the clinical background of the patient, including patient age, symptoms, distribution of the polyps, the number of polyps, and associated extraintestinal manifestations. Dysplasia and carcinoma may develop in these lesions.

Talking Points
  1. Pyloric gland adenomas are relatively rare lesions that most commonly arise in the stomach, and are probably under-recognized by pathologists.

  2. Pyloric adenomas are often relatively large (1.5-2.0cm) at the time of discovery.

  3. Dysplasia and foci of adenocarcinoma are common in pyloric gland adenomas.

References
  1. Vieth M, Kushima R, Borchard F, Stolte M. Pyloric gland adenoma: a clinico-pathological analysis of 90 cases. Virchows Arch 2003;442: 317-321.

  2. Chen ZM, Scudiere JR, Abraham SC, Montgomery E. Pyloric gland adenoma. An entity distinct from gastric foveolar type adenoma. Am J Surg Pathol, 2008, e-pub ahead of press.

  3. Kushima R, Remmele W, Stolte M, Borchard F. Pyloric gland type adenoma of the gallbladder with squamoid spindle cell metaplasia. Pathol Res Pract 1996;192:963-969.

  4. Fukatsu H, Kawamoto H, Tsutsumi K, et al. Intraductal tubular adenoma, pyloric gland-type, of the pancreas. Endoscopy 2007;39 (suppl 1):E88-89.

  5. Nakayama Y, Inoue H, Hamada Y, et al. Intraductal tubular adenoma of the pancreas, pyloric gland type: a clinicopathologic and immunohistochemical study of 6 cases. Am J Surg Pathol 2005;29:607-616.

  6. Amaris J. Intraductal mucinous papillary tumor and pyloric gland adenoma of the pancreas. Gastrointest Endosc 2002; 56:441-444.

  7. Mikami Y, Hata S, Fujiwara K, et al. Florid endocervical glandular hyperplasia with intestinal and pyloric gland metaplasia: worrisome benign mimic of "adenoma malignum". Gynecol Oncol 1999;74:504-511.

  8. Kushima R, Vieth M, Mukaisho K, et al. Pyloric gland adenoma arising in Barrett's esophagus with mucin immunohistochemical and molecular cytogenetic evaluation. Virchows Arch 2005;446:537-541.

  9. Kushima R, Ruthlein HJ, Stolte M, et al. Pyloric gland-type adenoma arising in heterotopic gastric mucosa of the duodenum with dysplastic progression of the gastric type. Virchows Arch 1999;435:452-457.

  10. Vieth M, Kushima R, de Jonge JP, et al. Adenoma with gastric differentiation (so-called pyloric gland adenoma) in a heterotopic gastric corpus mucosa in the rectum. Virchows Arch 2005;446:542-545.

  11. Kushima R, Vieth M, Borchard F, et al. Gastric-type well-differentiated adenocarcinoma and pyloric gland adenoma of the stomach. Gastric Cancer 2006;9:177-184.

  12. Wani Y, Notohara K, Fujisawa M. Aberrant expression of an "intestinal marker" Cdx2 in pyloric gland adenoma of the gallbladder. Virchows Arch 2008;453:521-527.

  13. Nagata S, Ajioka Y, Nishikura K, et al. Co-expression of gastric and biliary phenotype in pyloric-gland type adenoma of the gallbladder: immunohistochemical analysis of mucin profile and CD10. Oncol Rep 2007;17:721-729.

  14. Abraham SC, Montgomery EA, Singh VK, et al. Gastric adenomas. Intestinal-type and gastric-type adenomas differ in the risk of adenocarcinoma and presence of background mucosal pathology. Am J Surg Pathol 2002;26:1276-1285.