Grading of astrocytomas: A simple and reproducible method

Abstract

This study determines the effectiveness and reproducibility of a previously published method of grading gliomas. The method under study is for use on “ordinary astrocytoma” cell types, i.e., flbrillary, protoplasmic, gemistocytic, anaplastic astrocytomas and glioblastomas, and is based upon the recognition of the presence or absence of four morphologic criteria: nuclear atypia, mitoses, endothelial proliferation, and necrosis. The method results in a summary score which is translated into a grade as follows: 0 criteria = grade 1, 1 criterion = grade 2, 2 criteria = grade 3, 3 or 4 criteria = grade 4. The histologic material and clinical data were derived from a previously reported series of patients with astrocytomas, radiother‐apeutically treated at Mayo Clinic between the years 1960 and 1969. From this series, initially graded 1 to 4, according to the Kernohan system, 287 “ordinary astrocytomas” were entered into the study; 51 pilocytic astrocytomas and microcystic cerebellar‐type astrocytomas also were included for comparison. Among ordinary astrocytomas, the grading method under study distinguished 0.7% of grade 1, 17% of grade 2,18% of grade 3, and 65.3% of grade 4. A 15‐year period of follow‐up was available on all surviving patients. Statistical analysis showed that in ordinary astrocytomas, each of the four histologic criteria, as well as the resultant grade, were strongly correlated to survival (P < 0.0001). Median survival was 4 years in grade 2,1.6 years in grade 3, and 0.7 years in grade 4 tumors. Of the two patients with grade 1 ordinary astrocytomas, 1 had 11 years of survival, and the other was alive at 15 years. Furthermore, based upon the Cox Model, grade was found to be the major prognostic factor, superceding the effects of age, sex, and location. Among ordinary astrocytomas, the grading system under consideration clearly distinguished four distinct grades of malignancy, whereas, the Kernohan grading system accurately distinguished only two major groups of patients. Survival curve of patients with our grade 2 rumors coincided with the grade 1 and 2 Kernohan survival curves. Similarly, our grade 4 survival curve coincided with the Kernohan grade 3 and 4 survival curves. As a result, our proposed grading method generated an individualized curve corresponding to grade 3 tumors. Double‐blind grading between two independent observers was concordant in 94% of ordinary astrocytomas; reproducibility was 81% in low‐grade (grades 1 and 2) and 96% in high‐grade (grades 3 and 4) astrocytomas of ordinary type. Application of this simple and reproducible grading method for the study of ordinary forms of astrocytomas should permit reliable comparison of clinical and therapeutic data emanating from various treatment centers.