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Diagnostics Microscopy and imaging, Oncology

Case of the Month

The following light microscopy images were obtained from a specimen resected via endoscopy. Immunohistochemistry was positive for synaptophysin and chromogranin A. What differential diagnosis is indicated?

a. Well-differentiated neuroendocrine tumor
b. Primary adenocarcinoma
c. Metastatic adenocarcinoma
d. Primary gastrointestinal lymphoma

Ileal polyp. A) Hematoxylin and eosin 10x. Courtesy of Gang He.

Ileal polyp. B) hematoxylin and eosin 40x. Courtesy of Gang He.

Ileal polyp. C) positive synaptophysin immunohistochemistry. Courtesy of Gang He.

Ileal polyp. D) positive chromogranin A immunohistochemistry. Courtesy of Gang He.

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Antral biopsy. A) Hematoxylin and eosin 40x; B) periodic Acid-Schiff-Alcian Blue 40x; C) positive immunochemistry for microorganism. Courtesy of Gang He

a. No

Histologic findings such as intestinal metaplasia and a superficial band of mononuclear cell-rich infiltrate below the foveolar epithelium highly suggest chronic active gastritis secondary to Helicobacter pylori. The organism has adhesins that exhibit tissue tropism for the epithelial layer of the less acidic antrum (1) and decreased microenvironmental acidity often results in proximal migration to the gastric body, fundus, or cardia. The microbe is only occasionally found in areas of intestinal metaplasia (2), making immunohistochemical identification within this biopsy specimen a relatively uncommon finding.

Gastric intestinal metaplasia is a preneoplastic lesion usually precipitated by chronic H. pylori infection (3). Progression to severe chronic active gastritis indicates the most common differential diagnosis of mucosa-associated lymphoid tissue lymphoma (4). It is noteworthy to add that H. pylori-associated intestinal metaplasia, particularly with preceding glandular atrophy, is part of the Correa theory describing progression to gastric adenocarcinoma of the intestinal type (5).

Although there is no formal histologic criteria that indicates when a pattern of chronic active gastritis requires further testing, biopsies reviewed by an academic medical center in the United States found that 73.5 percent of histologically diagnosed cases were positive for the organism via immunohistochemistry stain (6).

Submitted by Erina McKinney, University of Kansas School of Medicine, Kansas City, Kansas; Gang He, American Diagnostic Consultation & Services, New York; and Ting Zhao, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

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  1. TL Testerman et al., “Adherence and Colonization” (2001). Available at:
  2. RM Genta et al., “Adherence of Helicobacter pylori to areas of incomplete intestinal metaplasia in the gastric mucosa,” Gastroenterology, 111, 1206 (1996). PMID: 8898634.
  3. KS Liu et al., “Helicobacter pylori associated gastric intestinal metaplasia: treatment and surveillance,” World J Gastroenterol, 22, 1311 (2016). PMID: 26811668.
  4. Q Hu et al., “Gastric mucosa-associated lymphoid tissue lymphoma and Helicobacter pylori infection: a review of current diagnosis and management,” Biomark Res, 4, 15 (2016). PMID: 27468353.
  5. XI Wang et al., “The role of routine immunohistochemistry for Helicobacter pylori in gastric biopsy,” Ann Diagn Pathol, 14, 256 (2010). PMID: 20637430.
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