gms | German Medical Science

Objective: Gangliogliomas are rare brain tumors occurring primarily in children and adults. They often present with epilepsy, and are generally thought to follow a benign clinical course. However, tumor recurrences and malignant progression have been observed. We have recently reported a large series of n=184 gangliogliomas (Luyken et al., 2004). In the present paper, we analyze our experience with clinically and/or histologically aggressive tumors, i.e. atypical WHO grade II, anaplastic WHO grade III and recurrent WHO grade I tumors.

Methods: A retrospective chart review was performed for 21 atypical WHO grade II, five anaplastic WHO grade III and three recurrent/progressive WHO grade I gangliogliomas. A neuropathological review including immunohistochemistry was carried out for 24 specimens.

Results: Mean follow-up was 53 months (range 1-142 months). Tumor recurrence rates for WHO grade II and III tumors were 24% (5/21) and 60% (3/5). We observed 5 secondary glioblastomas, i.e. a 45% (5/11) malignant progression rate. Mean age at surgery was 29.7 (range 14 to 60) years. 24 patients (83%) presented with seizures (including 17 cases =61% with refractory epilepsy). Patients, who later developed recurrent tumors or malignant progression were older (mean: 34.4 and 43.2 years, respectively), presented less often with chronic epilepsy (3/11=27% and 2/5=40%), and were diagnosed less frequently with temporal tumors (5/11=45% and 2/5=40%; overall series: 18/28=64%). Neuropathological examination revealed increased mitotic activity and diminished CD34 immunoreactivity during malignant progression, but cases with and without malignant progression/tumor recurrence did not differ with respect to their initial mitotic counts, Mib1/Ki67 or CD34 immunoreactivity. Initial specimens of several cases with an adverse course showed a partial gemistocytic differentiation and focal CD34 immunoreactivity associated with tumor cell processes.

Conclusions: Aggressive gangliogliomas, i.e. atypical (WHO grade II) and anaplastic (WHO grade III), and recurrent WHO grade I tumors are rare but seem to be characterized by an adverse clinical course, including a surprisingly high rate of malignant progression. Tumor recurrences and secondary glioblastomas tend to develop in older patients, who suffer less often from refractory epilepsy, and are more frequently diagnosed with non-temporal tumors. A gemistocytic differentiation may be associated with a non-benign course.