The DCLG registry is unique in the world for the number of included patients (>3000), standardized therapy and long term follow-up. Taking advantage of this unique data set our research group was the first to recognize that primary cutaneous lymphomas, i.e. malignant lymphomas presenting in the skin without concurrent extracutaneous disease, have a completely different clinical behavior and prognosis, as compared to histologically similar systemic lymphomas involving the skin secondarily, and therefore require a different type of treatment. In the last two decades our group described several new types of primary cutaneous T-cell lymphomas (CTCL) and primary cutaneous B-cell lymphomas (CBCL).

Classification

Capitalizing on the extensive tissue collection in the archives of the DCLG combined with long-term clinical follow-up data present within the DCLG database we formulated and validated diagnostic criteria and developed clinical guidelines to ensure optimal management and treatment of the different types of cutaneous lymphoma. The advances in classification combined with large cliniopathological studies provided clinicians with detailed information on clinical course, response to therapy and prognosis. Results from these studies have now been incorporated in the recently published WHO-EORTC classification of cutaneous lymphomas (2005) and WHO classification for malignant lymphomas (2008). Recent studies from our group focussed on the identification of molecular alterations that are essential in the pathogenesis of different types of CBCL and CTCL. These studies demonstrated clear cut differences in molecular alterations and identified potential molecular diagnostic markers, which will be further investigated. With support of KWF we recently started a multicenter EORTC supervised study focused on validation of diagnostic and prognostic biomarkers in erythrodermic CTCL  (2010-2014).

Molecular pathogenesis

In the coming years more detailed molecular characterization (including whole genome and transcriptome sequencing) of the subsequent stages of tumor progression will be performed. Special attention will be paid to the identification of alterations and aberrations predicting the clinical course. In addition, the role of epigenetic factors as well as protein-protein and protein-DNA interactions will be studied in more detail.. Several studies designed to map the entire microRNA profile (miRNome) of different disease entities are currently carried out and nearly completed. Together with functional studies aiming to delineate oncogenic signalling events and the benefits and working mechanisms of novel drugs  (e.g. drugs that target epigenetic abnormalities) in cutaneous lymphoma we aim to come to better management and treatment of patients. Since well-defined patient groups are indispensable to obtain useful results from the current high-throughput approaches, the cutaneous lymphoma group will continue to invest in database (management) and bio-banking.

Principal investigators

• Prof. dr. R. Willemze
• Prof. dr. M.H. Vermeer
• Dr. C.P. Tensen

Primary cutaneous lymphomas are a heterogeneous group of T- and B-cell lymphomas that clinically present in the skin. The main areas of interest of the cutaneous lymphoma research group are clinicopathological studies to improve diagnosis of cutaneous lymphoma patients and molecular studies to further insight in the pathogenesis of the disease and identification of molecular alterations that can be used as diagnostic marker, prognostic marker and therapeutic target.