Case 4 -

Glioblastoma with Oligodendroglioma Component (GBM-O; WHO Grade IV) Daniel J. Brat Emory University Hospital Atlanta, GA

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Clinical History: A 56-year-old female noticed progressive left-sided weakness in her upper extremity. Her husband stated that she had also had some personality changes and difficulty with verbal expression. An MRI of the brain revealed a large contrast-enhancing mass within the right parietal region, surrounded by T1-hypointense, T2-hyperintense signal changes. A craniotomy was performed and the lesion was subtotally resected. Case 4 - Figure 1 Coronal, post-contrast magnetic resonance (MR) image showing a contrast-enhancing mass involving the right parietal lobe surrounded by T1-hypointensity. Case 4 - Figure 2 Histologic section revealing a mixed neoplastic population of moderate cellular density dominated by astrocytoma cells but also showing scattered oligodendroglioma cells. Case 4 - Figure 3 Histologic sections showing a mixed population of astrocytoma and oligodendroglioma cells. Case 4 - Figure 4 Histologic sections showing a mixed population of astrocytoma and oligodendroglioma cells. Case 4 - Figure 5 Histologic section showing neoplastic cells with predominantly oligodendroglioma differentiation. Case 4 - Figure 6 Histologic section demonstrating microvascular hyperplasia within this glial neoplasm. Case 4 - Figure 7 Histologic sections demonstrating focal necrosis within this glial neoplasm. Case 4 - Figure 8 Histologic sections demonstrating focal necrosis within this glial neoplasm. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: Magnetic resonance imaging reveals an intrinsic, contrast- enhancing mass involving the right parietal lobe, surrounded by a substantial degree of T1-hypointensity. These are the features of a malignant neoplasm and could represent a primary or metastatic tumor. Histologic sections display an infiltrating gliomas with both oligodendroglioma and astrocytoma differentiation. These two types of neoplastic cells are intermingled in many regions, but there are other regions where one differentiation pattern dominates. This infiltrative glioma also shows mitotic activity, microvascular hyperplasia and necrosis. Differential Diagnoses: Glioblastoma with Oligodendroglioma Component,WHO Grade IV Anaplastic Oligoastrocytoma, WHO grade III Glioblastoma, WHO grade IV Anaplastic Oligodendroglioma, WHO grade III Final Diagnosis: Glioblastoma with Oligodendroglioma Component (GBM-O; WHO Grade IV) Case Discussion: This case represents an infiltrating glioma with both astrocytoma and oligodendroglioma differentiation. The MRI pattern of rim-enhancement and marked peritumoral edema suggests a malignant neoplasm and this is confirmed on histologic exam. In tissue sections, there is a moderate degree of hypercellularity and nuclear anaplasia in both the oligodendroglioma and astrocytoma components. Mitotic activity, microvascular hyperplasia and necrosis are all observed. According to the WHO 4th edition (2007), these features are consistent with the diagnosis of Glioblastoma with Oligodendroglioma Component, WHO grade IV. Review of the Literature/Treatment Options (if applicable): The infiltrating gliomas consist of astrocytomas, oligodendendrogliomas and oligoastrocytomas, with each category having its own grading system in the WHO classification. The grading schemes for the histologically "pure" astrocytomas and oligodendrogliomas in the 4th edition of the WHO classification remain largely the same as in the 3rd. [1, 2] Of note, there have been some fairly substantial changes incorporated into the grading of oligoastrocytomas that will affect both grade and classification. [3, 4] As in the past, oligoastrocytomas are designated as tumors that contain distinct regions of oligodendroglial and astrocytic differentiation. The minimal percentage of each component required for the diagnosis of a mixed glioma has been debated. [5] In the prior WHO edition, the criteria for anaplastic oligoastrocytoma (WHO grade III) included "features of anaplasia," which were listed as nuclear atypia, cellular pleomorphism, high cellular density, high mitotic activity, microvascular proliferation and necrosis. [6] These features could be present in the astrocytic component, the oligodendroglial component, or both. The results of recent clinicopathologic investigations have suggested that this grading scheme could be improved by dividing anaplastic oligoastrocytomas into prognostically distinct groups based on the presence of necrosis. [7, 8, 9] Miller et al studied the overall survival of 215 patients with anaplastic oligoastrocytoma as it related to age, gender, type of surgical procedure, necrosis and endothelial hyperplasia. [8] Necrosis was present in 33% of these tumors and endothelial proliferation was noted in 66%. Median survival was significantly shorter in patients with anaplastic oligoastrocytomas with necrosis (22.8 months; 95% confidence interval [CI], 14.9 - 33 months) than with anaplastic oligoastrocytomas that lacked necrosis (86.9 months; 95% CI, 48.4 -129 months). In contrast, the presence of endothelial proliferation was not found to be prognostically important among anaplastic mixed tumors. Thus, these data indicated that patients with anaplastic oligoastrocytomas with necrosis had shorter survival and that these tumors should be considered grade IV tumors rather than grade III. It can be debated whether anaplastic oligoastrocytomas with necrosis should be considered "oligoastrocytoma, grade IV" or should be classified as "glioblastoma with an oligodendroglial component, grade IV." In the 4th edition, the WHO classification indicates that oligoastrocytomas with necrosis should be classified as Glioblastoma with Oligodendroglioma Component (GBM-O), WHO grade IV. This topic is discussed in chapters on both anaplastic oligoastrocytoma and glioblastoma. In the latter, glioblastoma with oligodendroglioma component is described as a pattern of differentiation in glioblastoma. [1] It is critical to highlight that, while the above noted grading change applies to anaplastic oligoastrocytomas with necrosis, there is not a comparable change in grade when necrosis is present in an anaplastic oligodendroglioma. Necrosis in an anaplastic oligodendroglioma was not associated with a shorter survival and the grade of such neoplasms remains WHO grade III. [8] Conclusion(s): High grade infiltrative gliomas that have both astrocytoma and oligodendroglioma differentiation and also display necrosis are now designated Glioblastoma with Oligodendroglioma Component, WHO grade IV. References: Louis DN, Ohgaki, H., Wiestler, O.D., Cavenee, W.K.: "WHO Classification of Tumours of the Central Nervous System." Lyon: Intl. Agency for Research, 2007. Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathol (Berl) 2007;114:97-109. Brat DJ, Parisi JE, Kleinschmidt-DeMasters BK, et al.: Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. Arch Pathol Lab Med 2008;132:993-1007. Brat DJ, Prayson RA, Ryken TC, Olson JJ: Diagnosis of malignant glioma: role of neuropathology. J Neurooncol 2008;89:287-311. Coons SW, Johnson PC, Scheithauer BW, et al.: Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer 1997;79:1381-1393. Kleihues P, Cavenee WK: "Pathology and Genetics of Tumours of the Nervous System." Lyon: IARC Press, 2000. van den Bent MJ, Carpentier AF, Brandes AA, et al.: Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 2006;24:2715-2722. Miller CR, Dunham CP, Scheithauer BW, Perry A: Significance of necrosis in grading of oligodendroglial neoplasms: a clinicopathologic and genetic study of newly diagnosed high-grade gliomas. J Clin Oncol 2006;24:5419- 5426. Smith SF, Simpson JM, Brewer JA, et al.: The presence of necrosis and/or microvascular proliferation does not influence survival of patients with anaplastic oligodendroglial tumours: review of 98 patients. J Neurooncol 2006;80:75-82.