—  SPECIALTY CONFERENCE  —

Gastrointestinal Pathology

Case 4 - Ischemic Fundic Gland Polyps with Benign Signet Ring Cell Change

Christine M. Hobbs
Centennial Medical Center
Nashville, TN


Click on each slide thumbnail image for an enlarged view
Clinical History
A 77 year-old man presented to his primary care physician with a recent increase in chest pain. The patient had a several year history of gastroesophageal reflux disease and was being treated with a proton pump inhibitor. The patient's last upper endoscopy, performed three years previously, showed "histologic changes consistent with reflux esophagitis; negative for intestinal metaplasia." After the patient underwent testing essentially excluding a cardiac etiology for his increased chest pain, his internist referred him to a gastroenterologist for repeat upper endoscopy. At endoscopy, 12 polyps were found along the greater curvature and anterior wall of the gastric body. These polyps ranged in size from 3 mm to 10 mm. The gastric mucosa appeared otherwise unremarkable, as did the mucosa of the esophagus and gastroesophageal junction. The images show one of the gastric polyps, and the glass slides show a few of the polyps.


Case 4 - Figure 1 - Low power view of infarcted/ischemic fundic gland polyp.
Case 4 - Figure 2 - Glands with attached and unattached signet ring-like cells.


Case 4 - Figure 3 - Same glands at higher power.
Case 4 - Figure 4 - Gland filled with signet ring-like cells, surrounded by hemorrhage and neutrophils.

Pathologic Features
Grossly, the polyps removed from the stomach varied in color from pink to dark red. The microscopic images represent one of the grossly dark red polyps. These polyps show fundic-type (oxyntic) glands as well as mucin glands with variably dilated lumens that contain ballooned, signet ring-shaped cells. In some of the mucin glands, the signet ring cells are clearly attached to the luminal basement membrane leaving the luminal space empty. In others, the signet ring cells partially to completely fill the lumens, in some instances resulting in the appearance of clusters of cells rather than glands. The nuclei of the signet ring cells appear bland, without enlargement or conspicuous nucleoli. Hemorrhage and neutrophils fill the spaces between glands. Stromal fibrous tissue is not apparent. The grossly pink polyps show the histology of ordinary fundic gland polyps with normal appearing oxyntic glands, oxyntic glands with variably dilated lumens, and occasional nonoxyntic glands with dilated lumens. Parietal cells in some of the fundic-type glands protrude into the lumens (parietal cell hypertrophy), a feature commonly seen in patients taking proton pump inhibitors. Fibrous pink stroma runs between the glands.

Diagnosis: Ischemic fundic gland polyps with benign signet ring cell change

Discussion
Benign signet ring cell change (BSRCC) in the gastrointestinal tract is a non-neoplastic condition that morphologically simulates signet ring cell carcinoma. The literature contains relatively few reports of benign signet ring cell change in the gastrointestinal tract. Nevertheless, the phenomenon of benign mucin cells rounding up and taking the shape of signet rings (round with crescent-shaped nuclei compressed to the periphery) after they are damaged and desquamated is well known among gastrointestinal pathologists per personal conversations. In the GI tract, BSRCC has been described in association with pseudomembranous colitis, ulcerated tubular adenoma of the colon, Peutz-Jeghers polyps of the small intestine, gastric MALT lymphoma, and acute erosive gastropathy [1, 2, 3, 4, 5, 6, 7, 8, 9] . It has also been reported in gallbladder mucosa in patients with cholelithiasis [5, 9] . Most of the reported cases of pseudomembranous colitis with BSRCC have occurred in patients with evidence of Clostridium difficile-associated disease, but in some cases the pseudomembranous colitis was secondary to ischemia or ulcerative colitis [1]. Chen postulates that benign signet ring cell aggregates in Peutz-Jeghers polyps result from stretching and torsion of the polyps causing focal mucosal ischemia and sloughing of epithelium [6]. In this case, only the fundic gland polyps showing ischemic injury contain benign signet ring cells. Why some of the polyps in this patient show ischemic injury is a matter of speculation. Perhaps, this is due to stretching of the polyps. The background mucosa did not show features of erosive gastropathy.

The importance of identifying benign signet ring cell change is to distinguish it from signet ring cell carcinoma. Differentiating features of signet ring cell carcinoma include cellular atypia, with features such as nuclear enlargement, hyperchromasia, mitoses and prominent nucleoli. Distribution of the cells in an infiltrative pattern is also important. Unfortunately, in some cases of signet ring cell carcinoma, cytologic atypia is not prominent, and an infiltrative pattern may not be appreciated in small mucosal biopsy specimens. In most cases, a diagnosis of BSRCC can be confirmed by demonstrating confinement of signet ring cells to glands and/or surface exudates, without infiltration of stroma. Immunohistochemical stains for collagen IV and laminin can be useful in showing whether signet ring cells are within glands completely surrounded by intact basal lamina [4]. One exception is benign epithelial signet ring cells in MALT lymphomas. These cells may occur in isolation or grouped in clusters in the superficial portion of the lamina propria exclusively in lymphomatous areas [7]. The data from Zamboni et al. suggests that benign signet ring-shaped epithelial cells occurring in gastric MALT lymphomas represent a particular type of lymphoepithelial lesion in which the foveolar cells disaggregated by the lymphomatous infiltration acquire a globoid, signet ring appearance. Studies have shown that benign signet ring cells are negative for p53, Ki-67 and positive for E-cadherin, while malignant signet ring cells are positive for p53, exhibit high proliferation with Ki-67, and demonstrate absent or weak positivity for E-cadherin [1, 4, 8] . These immunostains were not used to make the diagnosis in this case; however, subsequent immunostaining with E-cadherin showed diffuse positivity among the benign signet ring cells.

References

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  9. Suri VS, Sakhuja P, Malhotra V, et al. Benign signet ring cell change with multilayering in the gallbladder mucosa. Pathol Res Pract 197:785-788, 2001.