CAR-T cell therapy and its complications: Role of the pathologist in diagnosis

CAR-T cell therapy has transformed the treatment of patients with hematologic malignancies but has also introduced a spectrum of post-therapy complications that frequently require histopathologic evaluation. While clinical toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are well characterized, the pathologist's role in interpreting post-CAR-T biopsy specimens remains underdefined and challenging. In this review, we focus on the histopathologic, immunophenotypic, and molecular features of post-CAR-T complications, including cytopenias, immune effector cell-associated syndromes, therapy-related myeloid neoplasms, secondary malignancies, and CAR-derived lymphoproliferations. We emphasize diagnostic pitfalls, differential diagnoses, and practical approaches to distinguishing reactive, inflammatory and neoplastic processes. Our aim in this review is to provide a pathology-centered framework to guide accurate diagnosis, prevent misclassification and support clinical decision-making in the evolving landscape of CAR-T therapy.