Morphologic and Molecular Genetic Diversity

● Context.—Glioblastoma (GBM), the most common pri-mary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3 distinct morphologic variants of GBM are currently recognized by the current World Health Orga-nization classification scheme, including GBM, giant cell GBM, and gliosarcoma. Additional variants, some of which have significant morphologic overlap with tumors that have more favorable prognosis and treatment response rates, particularly anaplastic oligodendroglioma, have been described since its publication in 2000 and may be includ-ed in the next classification. Objective.—To summarize the morphologic and molec-ular genetic diversity of both well-established and novel GBM variants and outline our approach to these hetero-geneous neoplasms and their distinction from other diffuse, high-grade gliomas. Data Sources.—Published literature and our own expe-rience in an active academic diagnostic surgical neuropa-thology practice were reviewed. Conclusions.—Precise subclassification of GBM is re-quired for accurate prognostication and appropriate treat-ment planning. (Arch Pathol Lab Med. 2007;131:397–406) Diffuse, infiltrative gliomas are the most common pri-mary intracranial neoplasms, accounting for 40 % of all primary and 78 % of all malignant central nervous sys-tem tumors.1 More than 80 % of these tumors are consid-ered high-grade (grades III and IV) when diagnosed ac-cording to the current World Health Organization (WHO) classification, a system based on morphologic evidence of differentiation along astrocytic, oligodendroglial, or mixed lineages. Classification and grading criteria for astrocytic neoplasms are well established, having been refined pe-riodically during the last 80 years from the classificatio