RIMARY central nervous system lymphoma is defined as an extranodal non-Hodgkin lymphoma located in the craniospinal axis without evidence of a systemic primary tumor. It usually presents as an intracerebral mass but may occur initially in the orbit, leptomeninges, or spinal cord. Overall, at the time of diagnosis, the leptomeninges are involved in approximately 40% of cases and the eyes in approximately 20%. 30 The spinal cord is involved in 1% of cases, and systemic metastases are found in

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... oximately 5%. Although the incidence of PCNSL has increased dramatically in recent years, it is still a rare tumor, much less common than nodal lymphoma. 37 Primary CNS lymphoma accounts for approximately 3 to 4% of primary brain tumors. These highly aggressive lesions leave patients with a median survival time of only a few months when left untreated or when treated with surgery alone. 25 Although the use of radiation and/or chemotherapy improves survival, some treatment regimens are associated with a high incidence of neurotoxicity, especially in patients older than 60 years of age. 2 In this article the pathological features of PCNSL are described, including the gross and microscopic appearance, as well as the role of stereotactic biopsy in diagnosis and management. Both the common (or "typical") and the uncommon forms of PCNSL will be discussed. The latter include low-grade and T-cell tumors, lymphomatosis cerebri, and dura-based lymphomas. Selected molecular studies addressing issues such as the derivation of PCNSL will be included. Epstein-Barr virus-related PCNSLs arising in the setting of immunodeficiency will be discussed separately because they differ in some respects from PCNSL seen in immunocompetent individuals. As a result, many recent studies are restricted to either immunocompetent or immunocompromised populations. Overview of Classification of PCNSLs Histologically, PCNSLs resemble systemic lymphomas, although a greater proportion of PCNSLs are highgrade and more than 95% are B-cell lymphomas. 30 The intraparenchymal cases, which represent the large majority of PCNSLs, are nearly always diffuse in architecture. Beyond these very general statements, any discussion of the classification of PCNSLs becomes complicated by a number of factors. At least three different classification systems (the Kiel, the Working Formulation, and the REAL) have been applied to PCNSL. Nevertheless, none of these classification systems, which were developed on the basis of studies of the nodal lymphomas, deals specifically with PCNSL. According to the Kiel classification, common subtypes include immunoblastic, centroblastic, lymphoblastic, and low-grade lymphomas. Many PCNSLs are unclassifiable by this system, however, and there is large variation from study to study in the relative frequencies of the various subtypes. 29 Application of the Working Formulation to Neurosurg. Focus / Volume 21 / The understanding of primary central nervous system lymphoma (PCNSL) has lagged behind that of the much more common systemic, nodal lymphomas. Reasons for this include the relative rarity of PCNSL and the fact that these lesions differ in some ways from their histologically similar systemic counterparts. The purpose of this paper is twofold: first, the author provides concise descriptions of the pathological features of both common and uncommon types of PCNSL while discussing issues such as the confusion surrounding histological classification of PCNSLs, problems related to intraoperative diagnosis, and the appropriate diagnostic work up. Second, the author discusses a small number of molecular studies to demonstrate the great promise they offer. Such studies have already clarified some issues, including the category of lymphocyte from which the majority of PCNSLs are derived. Hopefully in the future these studies will help guide treatment decisions. KEY WORDS • central nervous system • lymphoma • stereotactic biopsy • Epstein-Barr virus 1 Abbreviations used in this paper: ALCL = anaplastic large-cell lymphoma; CNS = central nervous system; DLBCL = diffuse large B-cell lymphoma; EBV = Epstein-Barr virus; GFAP = glial fibrillary acidic protein; HAART = highly active antiretroviral treatment; MZBCL = marginal zone B-cell lymphoma; PCNSL = primary CNS lymphoma; PIOL = primary intraocular lymphoma;