New variants of malignant glioneuronal tumors: a clinicopathological study of 40 cases.
OBJECTIVE
To demonstrate that malignant glioneuronal tumors comprise a large spectrum of neoplasms, without mature ganglion-like cells, that may histologically resemble any malignant glioma (World Health Organization Grade III or IV) but have a distinct biological behavior.


METHODS
This series includes all tumors diagnosed as malignant glioneuronal tumors (MGNTs) in our routine practice during a 2-year period during which neurofilament protein (NFP) immunostaining was performed in any case of suspected malignant glioma with unusual clinical, radiographic, and/or histological features. Immunostaining using neuronal markers (NFP, NeuN, synaptophysin, and chromogranin) and glial fibrillary acidic protein was done on paraffin sections after antigen retrieval. The presence of NFP-positive tumor cells, including those in mitosis, was used as a hallmark diagnostic criterion of MGNT.


RESULTS
All tumors coexpressed glial fibrillary acidic protein and NFP. Other neuronal markers tested were inconstantly expressed. No recurrence was observed at the primary site in 36.4% of patients who underwent gross total resection. Twelve patients (33.3%) developed intra-axial and/or systemic metastases, and 4 were free of disease at 39 to 184 months. Univariate analysis revealed that gross total surgical resection was the most important prognostic factor predicting survival (44 versus 15 mo; P < 0.0001), followed by a long duration of symptoms (>1 yr; P = 0.005), young age at symptom onset (children versus adults; P = 0.045), and absence of necrosis (P = 0.02). Gross total surgical resection (P = 0.001) and a long duration of symptoms (symptoms > 1 yr; P = 0.013) proved to be independent and statistically significant prognostic factors in the multivariate analysis.


CONCLUSIONS
NFP immunostaining is required to identify MGNTs accurately. Their distinction from malignant gliomas is of paramount clinical importance, particularly for neurosurgeons, because gross total surgical resection may be curative in some cases. Finally, MGNTs may account for the long-term survival and/or occurrence of metastases demonstrated in a subset of malignant gliomas.
Varlet
Pascale
P
Department of Pathology-Neuro-oncology, Sainte-Anne Hospital and Faculté Cochin Port-Royal, University Paris V, 75674 Paris, France.
Soni
Deepa
D
Miquel
Catherine
C
Roux
François-Xavier
FX
Meder
Jean-François
JF
Chneiweiss
Herve
H
Daumas-Duport
Catherine
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000601:surgery; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000601:surgery; D002648:Child; D005260:Female; D018303:Ganglioglioma / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000601:surgery; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D005909:Glioblastoma / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy; D016900:Neurofilament Proteins / Q000276:immunology; D009837:Oligodendroglioma / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000601:surgery; D011859:Radiography; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins