Summary
CAR T-cell therapy-related gastrointestinal toxicity presents with symptoms like abdominal pain and diarrhea, occurring 1.5 to eight months post-treatment. Histologic examination reveals a graft versus host disease-like pattern, with epithelial apoptosis and a paucity of B cells and plasma cells, necessitating careful differentiation from mimics like graft versus host disease and infection.
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.
CAR T-cell therapy-related gastrointestinal toxicity: histologic features and morphologic mimics
April 2026—Chimeric antigen receptor T-cell therapy is a contemporary treatment modality for hematologic malignancies, with potential future applications in solid tumors. While the clinical side effects of CAR T-cell therapy are well documented, the histologic correlations of gastrointestinal (GI) toxicity remain underreported. To better understand the clinicopathologic characteristics of CAR T-cell therapy-related GI toxicity, the authors conducted a study that prospectively identified five sets of biopsies from three patients presenting with CAR T-cell therapy-associated GI toxicity. Patients exhibited such symptoms as abdominal pain, hematochezia, nonbloody diarrhea, weight loss, and fever/chills, which occurred 1.5 to eight months after treatment. Histologic examination revealed a graft versus host disease-like pattern of injury in the colon that was characterized by epithelial apoptosis, crypt dropout, and neuroendocrine cell nests. One duodenal biopsy showed intraepithelial lymphocytosis and villous blunting, mimicking celiac disease. A notable paucity of CD20-positive B cells and CD38-positive plasma cells was observed in both colonic and small intestinal biopsies. Two patients required treatment with biologic agents, and one patient improved with corticosteroids but succumbed to an upper respiratory infection. The findings underscore the necessity of correlating symptom onset with timing of therapy to diagnose CAR T-cell therapy-associated GI toxicity. This diagnosis should be considered for any patient with a relevant history who presents with GI tract symptoms. One should look for such key histological features as epithelial apoptosis and a reduced number of plasma cells and B cells in the lamina propria, as well as intraepithelial lymphocytosis and villous blunting in cases with small bowel involvement. Histologic mimics, including graft versus host disease, medication-associated injury, and infection, should be excluded to ensure an accurate diagnosis and guide further treatment decisions.
Karimi SS, Larman TC, Jain T, et al. Chimeric antigen receptor (CAR) T-cell therapy-related gastrointestinal toxicity: Histologic features and morphologic mimics. Hum Pathol. 2025. doi.org/10.1016/j.humpath.2025.105791
Correspondence: Dr. Saman S. Karimi at [email protected], or Dr. Tatianna C. Larman at [email protected], or Dr. Tania Jain at [email protected]
Clinicopathologic and genomic characterization of granuloma-rich hepatocellular carcinoma
Limited literature is available on sarcoid-like granuloma associated with hepatocellular carcinoma. The authors conducted a study in which they analyzed the clinicopathologic characteristics and explored the potential significance of sarcoid-like granuloma in hepatocellular carcinoma. These tumors were termed granuloma-rich hepatocellular carcinoma (GrHCC). The authors reviewed clinicopathologic features in 30 GrHCC tumors diagnosed in 21 patients during 68 months at a single institution. The study included 17 males and four females (male age range, 43–71 years; female age range, 20–69 years). Tumors ranged from 0.6 to 23 cm (mean, 2.41 cm). A majority of tumors were well to moderately differentiated. A solitary well-formed epithelioid granuloma sufficed to classify the tumor as GrHCC. The intra-tumoral granulomas were compact, well formed, and discrete, and they consisted of collections of epithelioid histiocytes and multinucleated histiocytic giant cells. Mild lymphocytic inflammation was noted. A single granuloma to several granulomas were identified in the tumor. The granulomas ranged from 170 to 650 μm in size. Only one tumor showed necrotizing granulomas. Genomic analysis of four tumors revealed TP53 mutations, and two of those tumors also exhibited TERT promoter mutations. All but one patient were alive at last follow-up. (The deceased patient died from septic shock unrelated to hepatocellular carcinoma.) The authors concluded that this study provides valuable insights into the clinical and histopathological features and molecular characteristics of GrHCC. The presence of granulomas, though rare, appears to be associated with a distinctive tumor microenvironment that may impact tumor behavior and prognosis. The authors propose further research to elucidate the role of granulomatous inflammation in hepatocellular carcinoma pathogenesis and its potential as a prognostic marker or therapeutic target.
Vij M, Raju LP, Jothimani D, et al. Granuloma rich hepatocellular carcinoma (GrHCC): Clinicopathologic and genomic characterization. Ann Diagn Pathol. 2025. doi.org/10.1016/j.anndiagpath.2025.152504
Correspondence: Dr. Mukul Vij at [email protected]