Collagenous colitis in patients treated for cancer
Collagenous colitis is a rare complication of immunotherapy for cancer. The authors conducted a study to assess the role of immune checkpoint inhibitors (ICI) in the onset of this disease and describe the histopathological and immunophenotypic features of this entity and compare them with idiopathic collagenous colitis. They identified 15 cases of collagenous colitis diagnosed between 2000 and 2024 at their cancer center. Clinical charts and histopathological material were reviewed. Immunohistochemical profiling was performed to characterize immune cell populations (CD3, CD4, CD8, CD20, CD68, CD163, CD117, PD1, and PD-L1). A control group of 14 patients who did not have a history of cancer were included for comparison. The study focused on nine males and six females aged 23 to 81 years. Fourteen study participants were treated with ICI (anti-PD1/PD-L1 in 13 cases and anti-CTLA4 in one) and one with daratumumab. All presented with chronic diarrhea. The typical histological features of collagenous colitis—that is, a subepithelial band of thickened extracellular matrix and expansion of the lamina propria—were noted. The predominant immune cell population was CD8+ T lymphocytes in 12 cases. Patients treated with ICI showed higher neutrophilic infiltration, including crypt abscesses, and higher amounts of macrophages than control patients. The authors concluded that collagenous colitis in patients treated for cancer is closely associated with the use of anti-PD1/PD-L1 antibodies and shows some distinctive characteristics. Further understanding of the consequences of the PD1/PD-L1 axis blockade may shed more light on the pathogenesis of this rare disease.
Bani MA, Dartigues P, Soufan R, et al. Collagenous colitis in patients treated for cancer: role of immune checkpoint inhibitors. Clinical, histological and immunological features in 15 cases. Histopathology. 2025. doi.org/10.1111/his.15530
Correspondence: Dr. Mohamed-Amine Bani at mohamed-amine.bani@gustaveroussy.fr
Interobserver variability in evaluation of serrated epithelial change in IBD among gastrointestinal pathologists
Standardized histologic criteria for diagnosing serrated epithelial change in inflammatory bowel disease do not exist, but there are two commonly used definitions. The first, more basic, definition (DEF1) encompasses all endoscopically invisible or nontargeted serrated lesions without morphologic evidence of dysplasia that do not meet the diagnostic criteria of sessile serrated lesion (SSL) or traditional serrated adenoma (TSA). In contrast, the second definition (DEF2) incorporates more complex morphologic criteria, including disorganized crypt architecture with some crypts no longer perpendicular or extending down to the muscularis mucosae, irregular serration spanning the entire thickness of the mucosa, and goblet cell-rich epithelium, but it does not necessitate endoscopic correlation. The authors conducted a study to evaluate the reproducibility of diagnoses of serrated epithelial change (SEC) by gastrointestinal pathologists using these definitions. Seven gastrointestinal pathologists independently evaluated 38 cases, including 21 digitally scanned biopsy slides and 17 previously published images, demonstrating various types of serrated changes and their morphologic mimics. The diagnostic categories included SEC, hyperplastic polyp, SSL, TSA, hypermucinous dysplasia, and no serrated change or dysplasia (NSD). All cases were selected by a single pathologist who did not participate in the interobserver study. The pathologists initially assessed each case as if it were endoscopically normal and provided a diagnosis using DEF1. They then re-evaluated each case as if it were a nodular or polypoid lesion and again made a diagnosis using DEF1. The same process was repeated for each case using DEF2. A total of 532 diagnoses were made for each definition (seven pathologists, 938 cases, 92 endoscopic appearances). Fleiss’ kappa statistics were used to assess the level of agreement among the pathologists. The number of SEC diagnoses using DEF1 (n=110 of 532) was more than twice that of DEF2 (n=50 of 532). The number of SEC diagnoses per pathologist was also higher using DEF1 (mean, 16; range, 12–18) than with DEF2 (mean, 7; range, 0–14). Furthermore, the instances where four or more pathologists agreed on the diagnosis of SEC were more frequent with DEF1 (16 of 38 cases) than DEF2 (one of 38 cases). The overall agreement in diagnosing SEC versus no SEC using DEF1 was substantial (κ=0.69, P<.001), whereas the agreement using DEF2 was slight (κ=0.18, P<.001). Among potential SEC mimics, there was substantial agreement in diagnosing hyperplastic polyp (κ=0.69 using DEF1), SSL (κ=0.68), TSA (κ=1.00), hypermucinous dysplasia (κ=0.79), and NSD (κ=0.61) (P<.001). The authors concluded that the diagnosis of SEC is significantly more reproducible using DEF1 than DEF2. Pathologists utilizing DEF1 are also less likely to miss potentially important cases of SEC. Therefore, DEF1 could separate SEC from other serrated lesions and morphologic mimics in inflammatory bowel disease.
Bahceci D, Pai RK, Brown I, et al. Interobserver variability in the histologic evaluation of serrated epithelial change in inflammatory bowel disease among gastrointestinal pathologists: a comparison of two different definitions. Histopathology. 2025. doi.org/10.1111/his.15523
Correspondence: Dr. Won-Tak Choi at won-tak.choi@ucsf.edu