P21.03.A CDKN2A/B VERSUS MORPHOLOGY IN DIAGNOSING WHO GRADE 4 IDH MUTATED ASTROCYTOMAS: WHAT IS THE CLINICAL RELEVANCE?

Abstract

Abstract BACKGROUND In the 2021 WHO classification system, the glioma subgroup IDH-mutated astrocytomas grade 4 was introduced, and diagnosis can be based upon molecular or histopathological morphological criteria. We here explore if the reason for a diagnosis of WHO grade 4 IDH mutated astrocytoma influences survival. MATERIAL AND METHODS Twenty-five patients with a revised diagnosis of IDH-mutated astrocytoma grade 4 were included. Patients were divided in three groups based upon the; (i) Morphological high grade (necrosis and/or microproliferation in microscopy); (ii) Molecular high grade (homozygous CDKN2A/B homodelation); (iii) Both morphological and molecular high grade. Inclusion period was 2007-2018 for molecular high grade and 2012-2018 for morphological high grade. All patients had potential for at least 5 year follow-up. RESULTS The median survival following surgery was 5.2 years (Q1-Q3 2.9-7.0 years). The median age was 42 years (Q1-Q3 33-59). As expected the tumors had the frontal lobe predominance (72%). Seizures were the most common debut symptom, occurring in 48% of patients. There were 12 patients in group (i), nine patients in group (ii), and four patients in group (iii). Group (iii) with both morphological and molecular WHO grade 4 criteria was characterized by a significantly worse prognosis with a median estimated survival of 2.8 years (p = 0.002). There was no substantial difference in overall survival between groups (i) and (ii) (7.3 years vs 5.2 years, p = 0.237). CONCLUSION The median survival of IDH-mutated astrocytoma grade 4 is approximately five years, while prognosis seems to be significantly worse for the minority of patients where the tumor fulfills both molecular and morphological criteria. More research into larger cohorts is encouraged.