Primary Mediastinal (Thymic) Large B-Cell Lymphoma in Children and Adolescents: Current Aspects of Pathogenesis, Diagnosis, Therapy, and Long-Term Treatment Complications

Abstract

Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a rare subtype of mature B-cell lymphoma in children and adolescents, characterized by anterior mediastinal localization and a high incidence of life-threatening complications. This review synthesizes current evidence on the clinical and morphological features, molecular and genetic pathogenesis, diagnostic approaches, and therapeutic strategies for pediatric PMBCL. The review details characteristic morphological and immunohistochemical markers that distinguish PMBCL from other mediastinal lymphomas, as well as key genetic and epigenetic alterations, including dysregulation of the JAK-STAT and PD-1/PD-L1 signaling pathways. We evaluate therapeutic outcomes from standard chemotherapy regimens to protocols incorporating high-dose chemotherapy, targeted agents, and immunotherapy. Special emphasis is placed on treatment response in pediatric patients and the challenge of late toxicities, such as cardiotoxicity, secondary malignancies, and endocrine dysfunction. Modern PMBCL diagnostics rely on morphological and immunohistochemical studies, with tumor staging assessed via PET-CT. The integration of targeted therapies and immunotherapeutic agents, coupled with strategies to mitigate treatment-related toxicity, holds promise for improving survival rates and quality of life. Despite advances in understanding PMBCL biology, multicenter trials are essential to optimize pediatric treatment protocols and minimize complications in pediatric patients.