Kleinschmidt‐DeMasters, Bette K.

Abstract Context. —The World Health Organization (WHO) recently published its 4th edition of the classification of tumors of the central nervous system, incorporating a substantial number of important changes to the previous version (WHO 2000). The new WHO classification introduces 7 changes in the grading of central nervous system neoplasms, ranging in significance from minor to major, in categories of anaplastic oligoastrocytomas, meningiomas, choroid plexus tumors, pineal parenchymal tumors, ganglioglioma, cerebellar liponeurocytoma, and hemangiopericytomas. The 4th edition also introduces 10 newly codified entities, variants, and patterns, as well as 1 new genetic syndrome. A number of established brain tumors are reorganized, including medulloblastomas and primitive neuroectodermal tumors, in an attempt to more closely align classification with current understanding of central nervous system neoplasia. Objective. —To summarize and discuss the most significant updates in the 4th edition for the practicing surgical pathologist, including (1) changes in grading among established entities; (2) newly codified tumor entities, variants, patterns, and syndromes; and (3) changes in the classification of existing brain tumors. Data Sources. —The primary source for this review is the WHO Classification of Tumours of the Central Nervous System, 4th edition. Other important sources include the 3rd edition of this book and the primary literature that supported changes in the 4th edition. Conclusions. —The new edition of the WHO blue book reflects advancements in the understanding of brain tumors in terms of classification, grading, and new entities. The changes introduced are substantial and will have an impact on the practice of general surgical pathologists and neuropathologists.

PCNSLs in elderly persons are usually not mediated by Epstein Barr Virus (EBV), unlike PCNSLs in patients with AIDS or organ transplantation; hence IHC or ISH studies for EBV are not routinely performed. We have encountered patients 65 years or older who had autoimmune polyneuropathy (on CellCept for 3 years), polymyositis (oral prednisone alone for >15 years), rheumatoid arthritis (methotrexate >10 years), myasthenia gravis (azathioprine >10 years), or “senile immunosuppression” who developed multifocal, necrotic, EBV+ PCNSLs. Reducing or withdrawing immunosuppressive medications lead to recovery and regression of the PCNSL in some patients, but not all. The striking feature of this series is the variety of underlying diseases‐‐ and accompanying medications‐‐ that can be associated with EBV‐mediated PCNSLs in the elderly patient. Increased testing of PCNSLs for EBV by IHC or ISH may be warranted in any elderly person on any immunosuppressive medication.