Necrosis as a prognostic factor in glioblastoma multiforme

Abstract

Background: Many pathologists require the presence of tumor necrosis within an astrocytic neoplasm to establish the diagnosis of glioblastoma multiforme (GM). Two new grading systems for astrocytic neoplasms allow a tumor to be diagnosed at the highest level of anaplasia without requiring the presence of tumor necrosis.

Methods: To determine whether GMs without necrosis had biologic behavior most compatible with a diagnosis of GM or of anaplastic astrocytoma (AA), we examined the survival of 299 patients whose tumors were diagnosed as GM because they contained endothelial proliferation and who were treated according to prospective clinical protocols. Multivariate proportional-hazards survival analysis was used to assess the importance of tumor necrosis after adjustment for other prognostic factors.

Results: Of 275 patients with GMs containing endothelial proliferation, 88% had tumor necrosis. Absence of necrosis was associated with younger age and with less extensive surgical resection. The absence of necrosis predicted longer survival in univariate analysis (P = 0.02) and after adjustment for age, Karnofsky performance score, and extent of resection in a multivariate analysis (P = 0.04). However, the magnitude of the survival difference was not clinically important: patients without tumor necrosis had a median survival of 12.5 months, and those with tumor necrosis had a median survival of 10.9 months. Kaplan-Meier survival rates two years after diagnosis were 13.0% for patients with necrosis and 27.1% for patients without necrosis; the difference in 2-year survival was not statistically significant (difference in survival rates = 14.1%, 95% confidence interval -2.2% to 30.4%).

Conclusions: The survival of patients with astrocytic neoplasms containing endothelial proliferation and no necrosis conforms best to the pattern expected for patients with GM rather than AA. This supports the classification of these tumors as GM in the revised World Health Organization grading system and as grade 4 astrocytomas in the St. Anne-Mayo grading system.