Navigating the cutaneous B-cell lymphomas: avoiding the rocky shoals

In recent years great progress has been made in understanding the classification of lymphomas. The integration of morphologic, clinical, immunophenotypic, and molecular features provides a rational basis for defining disease entities and has led to worldwide consensus. Hematopathologists and dermatopathologists have worked together to define those lymphomas that are present most commonly in the skin. Some cutaneous lymphomas have distinctive features and differ from their nodal counterparts. This is most evident in the delineation of primary cutaneous follicle center lymphoma and primary cutaneous marginal zone lymphoma. Both are very indolent, with low risk to spread beyond the skin. Primary cutaneous marginal zone lymphoma shows evidence of immunoglobulin class switching, as distinct from involvement by other extranodal marginal zone lymphomas of MALT type, which may involve the skin secondarily. Some have suggested that primary cutaneous marginal zone lymphoma may be considered a benign clonal expansion, probably driven by antigen. Many cutaneous lymphomas share biological and clinical features with their systemic counterparts. For example, primary cutaneous large B-cell lymphoma, leg type, exhibits a similar gene expression and molecular profile as diffuse large B-cell lymphoma of the activated B-cell type, especially for those cases arising in other extranodal sites. In addition, Epstein-Barr virus plays a role in many cutaneous lesions including mucocutaneous ulcer, plasmablastic lymphoma, and even some cases of marginal zone lymphoma. These EBV-driven conditions may present primarily in the skin, but also involve other mainly extranodal sites. Thus, it is evident that some cutaneous and systemic lymphomas are driven by common pathogenetic mechanisms, necessitating an integrated approach for the classification of lymphoma in all sites.