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

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.