Primary Cutaneous Anaplastic Large Cell Lymphoma: A Review of Diagnosis and Treatment for the General Oncologist

Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a type of cutaneous T-cell lymphoma (CTCL) classified as a CD30+ lymphoproliferative disorder along with lymphomatoid papulosis. Although it is the second most common subtype of CTCL after mycosis fungoides/Sézary syndrome, it remains rare, with an incidence of fewer than 0.5 cases per million person-years. Despite its histologic similarity to systemic anaplastic large cell lymphoma, pcALCL follows a largely indolent course with excellent outcomes, with disease-specific survival rates of 86–95% in contemporary series. This narrative review summarizes the clinical presentation, diagnostic evaluation, and management of pcALCL based on a semi-structured literature search, with emphasis on prospective studies and clinically relevant retrospective data. Diagnosis remains challenging due to overlap with other CD30-positive lymphoproliferative disorders and reactive conditions, requiring careful clinicopathologic correlation and exclusion of systemic disease. While regional lymph node involvement may be present, available evidence suggests it does not significantly impact prognosis, highlighting the importance of avoiding overtreatment. Management strategies are guided by disease extent, with strong evidence supporting skin-directed therapies, particularly radiation, for localized disease. For multifocal or relapsed disease, brentuximab vedotin demonstrates the most robust prospective data and has reshaped the treatment landscape; however, alternative systemic therapies, including methotrexate and retinoids, remain relevant in selected patients. Overall, current management is supported largely by non-randomized data, and key gaps remain in risk stratification, optimal sequencing of therapies, and management of uncommon aggressive variants.