Cutaneous lymphoma. Understanding the new classification schemes.

Until recently, the practice of dermatology did not require a detailed understanding of lymphoma classification. Indeed, the existing classification schemes insufficiently classified cutaneous T-cell lymphomas, and most cutaneous B-cell lymphomas were thought to represent dissemination of a primary nodal lymphoma, requiring treatment and evaluation by hematologist-oncologists. It is now known that there are a wide range of B-cell and T-cell lymphomas that occur as primary tumors of the skin (Table 1), and that not all of these tumors behave in an indolent fashion. An understanding of the new lymphoma classification schemata will enable dermatologists to present the appropriate information regarding prognosis, staging procedures, and therapeutic options to their patients with cutaneous lymphoma. The lack of uniformity in the classification of lymphomas may have led to some confusion regarding the appropriate terminology for cutaneous lymphomas. Different institutions have used the Kiel, 56,57,94 the Working Formulation, 75 or the Lukes-Collins 63 lymphoma classifications. Often diagnoses were reported in more than one of the above classification schemes. In 1994 a revised lymphoma scheme was published that, unlike prior schemes, incorporated the ability of hematopathologists to recognize specific entities based on morphologic, immunologic, and genetic features. 40 This Revised European-American Lymphoma Classification (REAL) arose from a meeting convened in Berlin of 19 hematopathologists, members of the International Lymphoma Study Group. During this review of lymphomas, it became clear that each of the members of the group had independently developed ways of categorizing lymphomas that were essentially identical to those used by the other members of the group but that in many cases were distinct from any of the existing schemata for lymphoma classification (Table 2). Subsequently, the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Program Project Group devised a classification scheme specifically for primary cutaneous lymphoma. 113 In addition to the features used in the REAL classification scheme, the EORTC scheme incorporated the clinical presentation and biologic behavior of these cutaneous tumors. One of the aims of the recently published EORTC report was to define primary cutaneous tumors and draw attention to those lymphomas that have a clinical behavior that would not be predicted using classification schemes designed for nodal lymphomas. An understanding of how the terms primary and secondary have been applied to cutaneous lymphomas is critical to understanding the classification schemes. Most observers use the term secondary cutaneous lymphoma to describe lymphomas that develop in the skin as a secondary manifestation of a primary extracutaneous lymphoma. 6 However, the term secondary cutaneous lymphoma is also occasionally used to describe cutaneous tumors that develop as a transformation of a prior cutaneous lymphoma, for example, CD30-positive anaplastic large cell lymphoma arising in the setting of mycosis fungoides. 47,109 These transformed tumors are not considered to be secondary lymphomas in the EORTC cutaneous lymphoma classification scheme. The term primary cutaneous lymphoma has been used by some to describe lymphoma arising in the skin without evidence of concurrent extracutaneous lymphoma following staging including bone marrow biopsy and radiologic examination. 6,113 However, others define primary cutaneous lymphoma as lymphoma arising in the skin without evidence of extracutaneous lymphoma for 6 months following initial presentation. 18 A notable exception to these definitions of primary and secondary cutaneous lymphoma is mycosis fungoides, which is always presumed to represent a primary cutaneous lymphoma, despite the occasional patient who presents with nodal involvement in the absence of clinically evident cutaneous disease. The importance of appropriate classification of these tumors rests on the varied clinical outcome of primary cutaneous lymphoma. Some entities are indolent and never disseminate to extracutaneous sites, but others are rapidly fatal or disseminate widely with a protracted clinical course. The purpose of this article is to describe how the REAL, EORTC, and Kiel classification schemes apply to primary cutaneous lymphoma and to review the clinical, histologic, immunophenotypic, and genetic features of primary cutaneous lymphoma.