Despite these concerning features, both are from benign conditions. The first (Figure 1A) is from a fundic gland polyp in a patient on long-term proton pump inhibitor therapy. The gastric gland epithelial cells have exuberant cytoplasmic vacuolation which can be demonstrated using anti-H+ ATPase antibody immunohistochemistry and ABPAS to be parietal cells and to lack cytoplasmic mucin. They also retain normal expression of cadherins in contrast to neoplastic signet ring cells. This marked vacuolation has been reported by Runjan Chetty and others (1,2) Â as an important diagnostic pitfall capable of leading to an erroneous diagnosis of signet ring cell carcinoma to those unaware of these changes in florid cases such as this one. Notably in this case, the patient remains clinically and radiologically free of malignancy, and a previous fundic gland polyp from several years prior to this on retrieval from the archives showed identical changes.
Figure 2. An intact area of another biopsy from the patient in Figure 1B showing pseudomembranous colitis due to Clostridium difficile infection. Artefactual benign signet ring cell change in A, and in B the classical surface inflammatory pseudomembrane of fibrin, mucin and inflammatory cells.
The second patient was an elderly lady who presented with diarrhoea following a course of broad-spectrum antibiotics for a chest infection. She developed severe colitis and initial biopsies showed signet ring cells floating in mucin initially suspicious for malignancy (Figure 1A). Fortunately, this potential pitfall was recognised when in another biopsy, classical features of pseudomembranous colitis were recognised. Signet ring change is well recognised in pseudomembranous colitis (3,4) and is reported to be frequently seen in excision specimens for C. diff colitis when sampled extensively. In contrast to genuine signet ring carcinoma, benign signet ring change in colitis retains (as it did in our case) normal expression of E-cadherin and compartmentalised Ki67 expression in the lower segment of crypts. Our patient recovered with medical treatment for her colitis and did not need resection, but had a repeat endoscopy confirming restoration of normal mucosal morphology.
1. Hughes C, Greywoode G, Chetty R. Gastric pseudo-signet ring cells: A potential diagnostic pitfall. Virchows Archiv. 2011;459(3).
2. Rahman MA ur, Karam SM. Gastric parietal cell vacuolation mimicking gastric carcinoma. Histopathology. 2013;63(5).
3. Wang K, Weinrach D, Lal A, Musunuri S, Ramirez J, Ozer O, et al. Signet-Ring Cell Change Versus Signet-Ring Cell Carcinoma: A Comparative Analysis. American Journal of Surgical Pathology. 2003;27(11).
4. Damiani S, Campidelli C. Pseudomembranous colitis with signet-ring cells [6]. Vol. 41, Histopathology. 2002.