Primary Cutaneous B-Cell Lymphomas: An Updated Portrait of Classification, Biology, and Clinical Management

Primary cutaneous B-cell lymphomas (CBCL) represent a clinically and biologically heterogeneous group of extranodal non-Hodgkin lymphomas confined to the skin at the time of diagnosis. They account for approximately 25% of all primary cutaneous lymphomas and are subclassified into distinct entities according to the World Health Organization-European Organization of Research and Treatment of Cancer (WHO-EORTC) classification and International Consensus Classification (ICC). including primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), intravascular large B-cell lymphoma (IVLBCL) and Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU). These subtypes differ significantly in clinical behavior, histopathological features, molecular alterations, and prognosis. Indolent forms such as PCFCL and PCMZL are typically managed with local therapies and are associated with an excellent prognosis. In contrast, aggressive variants such as PCDLBCL-LT require systemic treatment and are linked to poorer outcomes. EBVMCU, despite its alarming histological appearance, generally follows a benign and self-limiting course. This review provides an updated overview of the current diagnostic criteria, clinical management strategies, and emerging molecular insights for each CBCL subtype. It also emphasizes the importance of a multidisciplinary approach and discusses the challenges of prognostication, along with the evolving but still limited role of innovative therapies.