Summary
A study introduced a computational framework to analyze collagen disorder architectural (CoDA) features in colon cancer patients, revealing significant associations with clinical, molecular, and genetic factors. Additionally, a dedicated histopathologic assessment of rituximab-associated CVID-like enteropathy highlighted key histologic features, emphasizing the importance of pathologist awareness of this entity.
Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; S. Emily Bachert, MD, associate pathologist, Brigham and Women’s Hospital, Boston; Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; Divya Sharma, MD, associate professor, Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center; and Paula Toro, MD, gastrointestinal and hepatobiliary fellow, Cleveland Clinic.
Collagen disorder architectural features: association with clinical, molecular, and genetic factors and colon cancer survival
February 2026—The authors conducted a study in which they introduced a computational pathology-based framework to extract collagen disorder architectural features from whole slide images of colon cancer patients. They investigated collagen disorder architectural (CoDA) features in 2,212 colon cancer patients across multiple institutions. The authors evaluated collagen fiber fragmentation, bundling, anisotropy, density, and rigidity for associations with clinical variables (overall stage, tumor/node/metastasis stage), molecular classifications (consensus molecular subtypes [CMS1–4]), and genetic mutations (KRAS, BRAF, NRAS) using the Mann-Whitney U test with Bonferroni correction. These analyses revealed significant differences in the distribution of CoDA features across multiple subgroups, suggesting that collagen architecture varies meaningfully with tumor stage, molecular subtype, and mutational status. To assess how well features of CoDA could distinguish between these subgroups, the authors implemented a random forest classification framework. High mean area under the receiver operating curve values (0.7 or more) across several variables indicated that CoDA features had strong discriminatory performance in separating clinically and biologically distinct groups. For survival analysis, Lasso-Cox models were trained on the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) data set to generate CoDA-based risk scores for overall survival and disease-free survival, which were used to stratify patients into high- and low-risk groups in a combined validation data set (The Cancer Genome Atlas, University Hospitals, and Emory University data sets). Kaplan-Meier curves demonstrated significant survival differences across clinical stages, CMS subtypes, and KRAS mutation status. Multivariable Cox proportional hazards models further confirmed the independent prognostic value of CoDA features after adjusting for clinical, molecular, and genetic covariates. These findings indicate that CoDA features are significantly associated with key clinical and molecular characteristics and can distinguish relevant patient subgroups. They also offer independent prognostic information, underscoring their potential utility in characterizing the tumor microenvironment and informing risk stratification in colon cancer.
Nag R, Chen C, Mejbel H, et al. Collagen disorder architecture features are associated with clinical, molecular, genetic factors and survival outcomes in colon cancer. NPJ Precis Oncol. 2025. doi.org/10.1038/s41698-025-01098-y
Correspondence: Dr. Anant Madabhushi at [email protected]
Histologic spectrum of rituximab-associated common variable immunodeficiency-like enteropathy
Rituximab is a monoclonal anti-CD20 antibody widely used to treat B-cell neoplasms and autoimmune conditions. The antibody recently has been linked to an enteropathy characterized by diarrhea, malabsorption, and hypogammaglobulinemia and closely resembling common variable immunodeficiency (CVID) enteropathy. The authors presented a dedicated histopathologic assessment of rituximab-associated CVID-like enteropathy. Study inclusion criteria were the presence of diarrhea, weight loss, or other gastrointestinal symptoms in the setting of current or prior rituximab use and associated hypogammaglobulinemia. Twenty-two patients (15 male and seven female; mean age at biopsy or resection, 63.4 years) across nine tertiary medical centers met the study inclusion criteria and had small bowel (n = 20) or colon (n = 17) specimens (biopsies or resections, or both) available for review; 71.4 percent of specimens were collected within five years of last rituximab dose. Cases were systematically evaluated by gastrointestinal pathologists at each institution. Key histologic features in the small bowel included a sparsity or absence of lamina propria plasma cells (n = 10; 50 percent), intraepithelial lymphocytosis (n = 12; 60 percent), villous atrophy (n = 11; 55 percent), an increase in crypt apoptotic bodies (n = 6; 30 percent), and active inflammation (n = 5; 25 percent). Common features in the colon included a sparsity or absence of lamina propria plasma cells (n = 7; 41.2 percent), an increase in crypt apoptotic bodies (n = 7; 41.2 percent), active inflammation (n = 5; 29.4 percent), and intraepithelial lymphocytosis (n = 4; 23.5 percent). Goblet cell loss was demonstrated in the small bowel and colon of one patient and the colon of a second patient. Follow-up biopsies (interval, two months to four years) were available for seven patients and largely recapitulated the histology of the index specimens, though one patient demonstrated improvement in villous blunting and intraepithelial lymphocytosis. In summary, the histologic spectrum of post-rituximab CVID-like enteropathy encompasses lamina propria plasma cell depletion, an increase in crypt apoptotic bodies, small bowel villous atrophy, and goblet cell loss. While the underlying pathophysiology remains uncertain, the clinicopathologic picture may reflect post-rituximab B-cell/plasma cell impairment. Although histologic findings may be subtle and variable, pathologists should be aware of this entity and look for a history of rituximab use in patients whose biopsies exhibit these CVID enteropathy-like features.
Jafari P, Hakimian D, Westerhoff M, et al. The histologic spectrum of rituximab-associated common variable immunodeficiency-like enteropathy. Mod Pathol. 2025. doi.org/10.1016/j.modpat.2025.100770
Correspondence: Dr. Pari Jafari at [email protected]