Serrated Epithelial Change Is Associated With High Rates of Neoplasia in Ulcerative Colitis Patients: A Case-controlled Study and Systematic Review With Meta-analysis

Background Patients with long-standing ulcerative colitis (UC) are at an increased risk of colorectal cancer. Risk stratification is important to identify patients who require more frequent endoscopic surveillance. Serrated epithelial change (SEC) found in patients with long-standing colitis may be associated with neoplasia and serve as a marker to stratify patients at higher risk of colorectal cancer (CRC). Methods A case-control study was performed to compare the rates of neoplasia between UC patients with SEC and UC patients without SEC who were matched for age, disease duration, and disease extent. Paired tests, conditional logistic regression, and Kaplan-Meier analyses were used to compare groups. A systematic review with meta-analysis was performed, combining our local data with previously published data. Results This study included 196 UC patients without prior neoplasia, 98 with SEC and 98 without SEC. Ulcerative colitis patients with SEC had a significantly higher rate of synchronous or metachronous neoplasia than UC patients without SEC (26.5% vs 3.1%; P < 0.001). Synchronous or metachronous high-grade dysplasia and CRC were found more frequently in UC patients with SEC than UC patients without SEC (11.2% vs 2.0%; P = 0.02). A meta-analysis was consistent with these findings, showing a higher rate of neoplasia in patients with SEC compared with those without SEC (16.4% vs 3.9%; P < 0.001). Conclusion Serrated epithelial change is associated with a significantly increased risk of synchronous and metachronous neoplasia including high-grade dysplasia and CRC in patients with UC. Histopathological findings of SEC should warrant closer endoscopic surveillance for CRC.

Immunohistochemical Characterization of Reactive Epithelial Changes in Odontogenic Keratocysts

Odontogenic keratocysts (OKCs) have a diagnostic thin epithelial lining characterised by a linear epithelial connective tissue interface generally lacking inflammatory changes, basal palisading of the nuclei and a wavy parakeratotic layer on the surface. This typical epithelium may convert to a thicker non-keratinizing one with rete pegs and a relatively flat surface after operative decompression. The aim was to characterize this type of epithelial change by immunohistochemistry for bcl2, keratin17, 10 and 19. Eleven out of 33 archived OKCs demonstrated an altered epithelium related to previous biopsy, decompressing drainage or inflammation. The typical basal bcl2 staining was lost in 10/11 cases; transepithelial CK17 was lost or markedly reduced in 9/11 cases. CK10 displayed a segmental upper layer staining in OKCs, and its loss or partial loss in the altered epithelium did not differ from negative areas of OKCs. CK19 displayed various staining patterns in the altered epithelium from lost to maintained in a patchy transepithelial distribution, the latter of which did not differ from the typical OKC staining pattern. Three of four non-keratinizing epithelial linings with basal palisading displayed immunostaining reminiscent of typical OKC epithelium. The lack of a typical epithelium is not sufficient to exclude the diagnosis of OKC if the sampling is not generous (e.g. biopsy), and the presence of non-keratinizing epithelium with basal palisading and an immunophenotype characteristic of OKC (basal bcl2, patchy or diffuse CK17 and upper layer CK10 positivity) may be consistent with the OKC diagnosis even in the absence of typical epithelial lining.

Diagnostic Dilemma of Epithelial Signet Ring Cells in Calculous Cholecystitis

Classic neoplastic signet ring cells are characterized by peripheral nuclear displacement by accumulation of cytoplasmic mucin in some adenocarcinomas. However, epithelial nonneoplastic signet ring cells may accumulate in the setting of mucosal erosion and ischemia as a reactive change of damaged columnar mucosa. Nonneoplastic signet ring cells may also occur as part of an inflammatory reaction due to histiocytes with signet-ring cell mucicarminophilia. A 58-year-old female presented with a 3-day history of increasing right upper quadrant abdominal pain. MRI showed distended gallbladder with 2 large stones, thickening of the gallbladder wall, and pericholecystic edema, consistent with acute cholecystitis. Laparoscopic cholecystectomy revealed a 15 × 6.0 × 3.5-cm gallbladder with eroded fundic mucosa, marked wall thickening (2 cm), and two intraluminal yellow stones, measuring 2.5 cm and 2.2. cm in diameter, respectively. The differential diagnosis included incidental gallbladder adenocarcinoma. Clusters of signet ring cells were seen in the fibrinous debris and were focally present in the superficial lamina propria. Intestinal metaplasia but no dysplasia was also observed. Loose clusters of pancytokeratin-positive, CD68-negative signet ring cells contained intracytoplasmic mucicarmine-positive mucin. Negative p53, low Ki-67, and positive E-cadherin supported the diagnosis of reactive signet ring cells. Deeply infiltrating pancytokeratin-positive epithelial cells were not identified. Final diagnosis was acute and chronic calculous cholecystitis with mucosal erosion and reactive signet ring cell epithelial change. Nonneoplastic epithelial signet ring cells may represent a diagnostic pitfall in chronically inflamed and eroded columnar cell mucosa of the gallbladder. A panel of immunostains and evaluation for cytologic atypia and unequivocal invasion are most helpful in differentiating this unusual reactive epithelial change, which occurs in response to inflammation, erosion, and/or ischemia, from signet ring cell carcinoma.