Elevated citrate in pediatric astrocytomas with malignant progression

Abstract

In vivo magnetic resonance spectroscopy (MRS) provides information about metabolite concentrations in tissue. Recently citrate was detected by MRS in subgroups of pediatric brain tumors. Citrate is an intermediate in the tricarboxylic acid (TCA) cycle and accumulates in tissue when the glycolytic rate exceeds the TCA cycle activity, a feature of malignant tumors. Currently, no practical indicators allow clinicians to predict risk for malignant progression of pediatric astrocytomas (World Health Organization [WHO] grade II). Medical records and citrate concentrations measured with in vivo MRS of 29 pediatric astrocytomas were reviewed. This included 6 patients with astrocytomas (WHO II) who had stable disease (indolent LGA) for >2 years, 7 with aggressive grade II astrocytomas (aggressive LGA), 13 with anaplastic astrocytomas (WHO III), and 3 with glioblastoma (WHO IV) with disease progression within 2 years. Citrate was observed in all patients with aggressive LGA, and the mean citrate concentration was significantly higher in this group than among those with indolent LGA (mean ± standard deviation, 4.1 ± 1.1 vs 0.6 ± 0.8 mmol/kg; P < .0001). There was no consistent pattern for citrate in anaplastic astrocytoma and glioblastoma, with citrate prominent in some lesions whereas undetectable in others. It is unclear whether citrate accumulation occurred because of fundamental defects of citrate regulation or was secondary to altered physiological conditions. Nonetheless, prominent citrate identified a subgroup of pediatric grade II astrocytomas destined for aggressive behavior. Citrate was not specific for poor outcome because it was not detectable in all high-grade astrocytomas. In high-grade astrocytoma, tumors with prominent citrate may constitute a metabolic subclass.