Evidence for a Clinically Distinct New Subtype of Grade II Astrocytomas in Patients with Long-term Epilepsy

OBJECTIVE: The authors tested the hypothesis that among Grade II astrocytomas with a particularly long seizure history, a subgroup is hidden with a different prognosis and possibly histological characteristics. To do so, clinical and histological characteristics of two groups of World Health Organization Grade II astrocytoma patients were analyzed: the long-term epilepsy-associated tumor (LEAT) astrocytoma group, with a mean duration of 12.5 years of seizures (n = 19), and the ordinary astrocytomas (n = 87), with a mean length of seizure history of 1.5 years (Non-LEAT). METHODS: All astrocytomas operated on between 1988 and 1999 were collected and followed up for 2 to 13 years (median, 7.0 yr). The 19 LEAT astrocytomas belonged to a group of 207 long-term epilepsy-associated tumors from the epilepsy surgery program. The 87 Non-LEAT cases were 60 so-called ordinary or diffuse World Health Organization Grade II astrocytomas and 27 oligoastrocytomas without long-term epilepsy operated on during the same time period. All tumor cases have been reviewed and partly reclassified as a result of the use of modern immunohistochemical techniques. Statistical analyses for possible discriminating factors included χ2 test, Fisher's exact test, Kaplan-Meier curves, and multifactorial analysis. RESULTS: Histological subtyping revealed a possible new isomorphic astrocytoma subtype in seven patients. By use of Kaplan-Meier curves, this isomorphic subtype had 50% fewer recurrences at 7.5 years and an estimated long-term survival of 80%. LEAT astrocytomas differed from ordinary Non-LEAT astrocytomas in overall length of history, younger age at first seizure, and higher percentage of 10-year survivors (80%). Temporal location did not influence outcome, and the presence of epilepsy per se was also not a prognostic factor. CONCLUSION: Differences between astrocytomas with a very long seizure history and those with a very short seizure history do exist. Significant factors for prognosis were age at surgery and presence of postoperative tumor residue but not the presence of epilepsy per se. A new subtype of astrocytomas, provisionally called isomorphic LEA astrocytoma, has putatively been identified with significantly better survival and lower recurrence rate. The negative prognostic factor of a gemistocytic differentiation pattern in diffuse astrocytomas was confirmed.