Signet-Ring Cell Change Versus Signet-Ring Cell Carcinoma

Abstract

Signet-ring cell change (SCC) is a nonneoplastic condition that morphologically simulates signet-ring cell carcinoma (SRCA). The few case reports on SCC have focused on morphologic characteristics in distinguishing benign from malignant. In biopsy specimens, however, SCC can be easily confused with SRCA, which often demonstrates innocuous cytologic features. The object of this study is twofold: 1) to report 14 additional cases of SCC, comparing their morphologic and phenotypic features with that of SRCA; and 2) to evaluate the incidence of SCC in pseudomembranous colitis. Paraffin sections of biopsy or resection specimens containing focal or extensive SCC and 5 cases of colonic SRCA were stained with hematoxylin and eosin, periodic-acid Schiff stain with and without diastase digestion, and by standard ABC immunoperoxidase procedure using antibodies to E-cadherin, p53, and Ki-67. Both cells in SCC and SRCA were strongly positive for neutral mucins. Cells in SCC were strongly positive for E-cadherin and negative for p53 and Ki-67. In contrast, cells in SRCA were strongly positive for p53, exhibited high proliferation, and demonstrated absent or weak positivity for E-cadherin. Although SCC is not well recognized in pseudomembranous colitis, the incidence is fairly high: 14 of 50 (28%) cases showed variable numbers of signet-ring cells. Extensive SCC, although rare, can occur in different clinical conditions and can be easily mistaken for SRCA. When in doubt, routine immunohistochemical stains such as p53, Ki-67, and E-cadherin can help to differentiate SCC from SRCA.

Absence of E-Cadherin Expression Distinguishes Noncohesive from Cohesive Pancreatic Cancer

“…Indeed, we observed a total loss of E-cadherin expression in two signet ring cancers of the pancreatobiliary tract. Alternative mechanisms of signet cell change (unrelated to E-cadherin inactivation) have also been described, such as tissue hypoxia, and could account for the morphologic changes observed in five E-cadherin -positive signet ring cancers in this study (36,37).…”

Nonneoplastic signet-ring cells in the gallbladder and uterine cervix. A potential source of overdiagnosis

“…Signet-ring cells mimicking adenocarcinoma have been found in ischemic ileitis, Peutz-Jeghers polyps, ulcerated tubular adenomas of the colon, and pseudomembranous colitis [33,[37][38][39][40][41][42][43]. In the latter condition, they have been said to occur in as many as one quarter of the cases [1]. The biological mechanism for their production is still unclear, but it seems related to mucosal ischemia.…”

“…Signet-ring cell is a descriptive term used to designate the light microscopic appearance of cells characterized by a crescent-shaped nucleus displaced to the cell periphery secondarily to the cytoplasmic accumulation of mucin, lipids, vacuoles, inclusions, or other materials [1]. The term signet-ring cell adenocarcinoma has been traditionally applied to a subtype of aggressive high-grade adenocarcinoma typically located in the stomach (also known as diffuse carcinoma and linitis plastica) [2] and breast [3].…”

Warthin Tumor with Signet-Ring Cell Features as a Pitfall in Salivary Gland Cytopathology

“…SRC features, usually seen in high-grade carcinomas, may occur in benign lesions [8,9]. In particular, SRCs have occasionally been observed in salivary-gland benign tumors either as a pure population of cells [10,11] or mixed with a WT component [12].…”