Oligodendroglial neoplasms with ganglioglioma-like maturation: a diagnostic pitfall

Although oligodendroglial neoplasms are traditionally considered purely glial, increasing evidence suggests that they are capable of neuronal or neurocytic differentiation. Nevertheless, ganglioglioma-like foci (GGLF) have not been previously described. Herein, we report seven examples where the primary differential diagnosis was a ganglioglioma with an oligodendroglial component. These five male and two female patients ranged in age from 29 to 63 (median 44) years at initial presentation and neuroimaging features were those of diffuse gliomas in general. At presentation, the glial component was oligodendroglioma in six and oligoastrocytoma in one; one was low-grade and six were anaplastic. A sharp demarcation from adjacent GGLF was common, although some intermingling was always present. The GGLF included enlarged dysmorphic and occasionally binucleate ganglion cells, Nissl substance, expression of neuronal antigens, GFAP-positive astrocytic elements, and low Ki-67 labeling indices. In contrast to classic ganglioglioma, however, cases lacked eosinophilic granular bodies and CD34-positive tumor cells. Scattered bizarre astrocytes were also common and one case had focal neurocytic differentiation. By FISH analysis, five cases showed 1p/19q codeletion. In the four cases with deletions and ample dysmorphic ganglion cells for analysis, the deletions were found in both components. At last follow-up, two patients suffered recurrences, one developed radiation necrosis mimicking recurrence, and one died of disease 7.5 years after initial surgery. We conclude that GGLF represents yet another form of neuronal differentiation in oligodendroglial neoplasms. Recognition of this pattern will prevent a misdiagnosis of ganglioglioma with its potential for under-treatment.