Cutaneous CD30-positive lymphoproliferations: therapeutic strategies and prognostic factors

Abstract

Cutaneous lymphomas originate from cancer of the lymphocytes in the skin without lymph node/organ involvement at time of diagnosis. There are many types of cutaneous lymphomas, with this thesis focusing on CD30-positive cutaneous lymphomas, consisting of a spectrum with lymphomatoid papulosis (LyP) on one side, and primary cutaneous anaplastic large cell lymphoma (C-ALCL) on the other. LyP is characterized by multiple skin lesion that resolve spontaneously, and C-ALCL by a solitary or grouped tumor that persists. This thesis shows that approximately 15% of LyP patients develop a second skin lymphoma/blood cancer, but also have an increased risk of developing other cancers (squamous cell carcinoma/melanoma/colon/lung/bladder cancer). At molecular level, a subcategory of patients was found in C-ALCL with ALK translocations, suggestive of a systemic lymphoma. It appears that these patients also have a favorable prognosis and can be treated with radiotherapy. The optimal dose of radiotherapy was also demonstrated (8 Gray). In addition, different types of mutations (PI-3-K/MAPK/G pathways) seem to occur in C-ALCL compared to more aggressive lymphomas (JAK-STAT). C-ALCL patients with ≤5 tumors are best treated with radiotherapy, and patients with >5 lesions with methotrexate. Targeted therapies remain for patients not responding to methotrexate or with systemic involvement.</p