A histopathological contribution to supratentorial glioma grading, definition of mixed gliomas and recognition of low grade glioma with Rosenthal fibers

Abstract

Background: Previous glioma studies have described separate grading systems for oligodendrogliomas and astrocytomas. Many of these gliomas contain mixtures of neoplastic astrocytes and oligodendrocytes. Prognosis may be related to the percentages of these neoplastic components. Previous survival/grading studies have been limited to histopathological features but have not evaluated the importance of percentages of neoplastic components. This study attempted to perceive the relative importance of percentages of neoplastic astrocytes and oligodendrocytes for definition of astroglial, oligodendroglial and mixed oligoastroglial tumors. After determination of these limits we explored the possibility to develop a grading system for common supratentorial gliomas based on reproducible histopathological features.

Methods: A retrospective study was performed of 362 cases of unselected supratentorial glioma. One hundred and thirty-eight binary and nine continuous histopathological variables, amongst which percentages of neoplastic astrocytes and oligodendrocytes, were scored and related to survival. Only well reproducible histological features were accepted in Cox regression to define glioma grades.

Results and conclusions: Supratentorial gliomas appeared to be composed of variable percentages of neoplastic oligodendrocytes and astrocytes, but this spectrum did not correspond to a continuous change in prognosis. Gliomas containing 30% or more neoplastic oligodendrocytes had a slightly better outcome (p < 0.0432) but higher percentages did not further improve prognosis. Percentages of neoplastic astrocytes were not correlated to survival. We therefore propose to designate gliomas containing 30% or more neoplastic oligodendrocytes as oligodendroglial tumors, and others as astroglial tumors. From a prognostic point of view there is no need to recognize mixed oligoastrocytomas. An interesting finding was the recognition of a low grade glioma group with Rosenthal fibers, which had the longest postoperative survival. Another prognosticator of interest concerns the mitotic rate as a continuous variable. Atypical mitoses indicated the worst survival, after necrosis. It was possible to develop a grading system for all supratentorial gliomas using six reproducible histological parameters: necrosis, atypical mitoses, the mitotic rate, endothelial proliferative activity, percentage of neoplastic oligodendrocytes and Rosenthal fibers. This resulted in four grades for astroglial tumors (p < 0.002) and three grades for oligodendroglial tumors (p < 0.008) which differed significantly within each group with respect to survival.