Primary Cutaneous Lymphomas and Lymphoproliferative Disorders: Current Insights for Classification and Management.

Abstract

Primary cutaneous lymphomas (PCLs) represent a heterogeneous group of extranodal non-Hodgkin lymphomas with distinct clinical, histological, and molecular profiles. Recent advancements in genomic profiling have led to significant revisions in diagnostic frameworks and therapeutic paradigms. This review aims to summarize the current landscape of primary cutaneous B-cell and T-cell lymphomas and lymphoproliferative disorders (LPDs), focusing on the diagnostic updates in the WHO 5th edition and the International Consensus Classification (ICC 2022), alongside evolving risk-adapted treatment strategies. A comprehensive review of the recent literature and major international consensus guidelines was conducted, evaluating diagnostic shifts, disease reclassifications, and novel therapeutic interventions across various PCL subtypes. The latest WHO 5th and ICC 2022 classifications emphasize the clinical behavior of indolent entities, shifting terminology from "lymphoma" to "lymphoproliferative disorder" for conditions such as primary cutaneous acral CD8+ T-cell LPD and primary cutaneous CD4+ small/medium T-cell LPD to prevent overtreatment. Several previously provisional categories (e.g., primary cutaneous gamma/delta T-cell lymphoma and EBV-positive mucocutaneous ulcer) have achieved definitive diagnostic status. Parallel to these revisions, therapeutic management has shifted toward toxicity-reducing, risk-adapted strategies. For indolent subtypes, ultra-low-dose radiotherapy (4 Gy) and skin-directed therapies remain highly effective. In aggressive or refractory subtypes, such as Mycosis Fungoides and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT), precision oncology-utilizing targeted agents (e.g., brentuximab vedotin, mogamulizumab, lenalidomide, ibrutinib) and cellular/immunotherapies-is rapidly changing outcomes. Integrating the updated diagnostic classifications with modern risk-stratified and targeted treatment paradigms is crucial for optimizing clinical management and avoiding overtreatment in indolent PCLs while improving survival in aggressive subtypes.