CLINICOPATHOLOGICAL STUDY NEW VARIANTS OF MALIGNANT GLIONEURONAL TUMORS:ACLINICOPATHOLOGICAL STUDY OF 40 CASES Pascale Varlet, M.D. Department of Pathology-Neuro- oncology, Sainte-Anne Hospital and Faculté Cochin Port-Royal, University Paris V, Paris, France Deepa Soni, M.D. Department of Pathology-Neuro- oncology, Sainte-Anne Hospital and Faculté Cochin Port-Royal, University Paris V, Paris, France, and Department of Neurosurgery, Brigham and Women’s Hospital, Children’s Hospital, Harvard Medical School, Boston, Massachusetts Catherine Miquel, M.D., Department of Pathology-Neuro- oncology, Sainte-Anne Hospital and Faculté Cochin Port-Royal, University Paris V, Paris, France François-Xavier Roux, M.D. Department of Neurosurgery, Sainte-Anne Hospital and Faculté Cochin Port-Royal, University Paris V, Paris, France Jean-François Meder, M.D., Ph.D. Department of Neuropathology, Sainte-Anne Hospital and Faculté Cochin Port-Royal, University Paris V, Paris, France Herve Chneiweiss, M.D., Ph.D. Department of Neuropharmacology, Institut National de la Santé et de la Recherche Médicale, Unite 114, College de France, Paris, France Catherine Daumas-Duport, M.D., Ph.D. Department of Pathology-Neuro- oncology, Sainte-Anne Hospital and Faculté Cochin Port-Royal, University Paris V, Paris, France Reprint requests: Catherine Daumas-Duport, M.D., Service de Pathologie, Hôpital Sainte-Anne, 1, rue Cabanis, 75674 Paris Cedex 14, France. Email: daumas@chsa.broca.inserm.fr Received, January 14, 2004. Accepted, June 1, 2004. 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 neuro- filament 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 chromo- granin) 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 neu- ronal 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. CONCLUSION: 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. KEY WORDS: Glioneuronal tumors, Malignant gliomas, Neurofilament protein, Neuronal markers Neurosurgery 55:1377-1392, 2004 DOI: 10.1227/01.NEU.0000143033.36582.40 www.neurosurgery-online.com M alignant glioneuronal neoplasms are considered to be rare lesions. In fact, anaplastic gangliogliomas and the recently described “rosetted glioneuronal tu- mors” (49) are the only well-defined tumor entities in this category. Several case reports have described malignant glioneuronal tu- mors (MGNTs) that were unclassifiable ac- cording to existing schemas, with the number of different names attributed to these tumors nearly equaling the number of cases described (for a review, see Reference 34). However, with the exception of two cases (37), all of the various MGNTs described to date have con- tained mature ganglion-like cells. The aim of this study is to present data in support of the concept that MGNTs comprise a large and previously unsuspected spectrum of neoplasms in children and adults that do not exhibit mature ganglion-like cells. The tumors NEUROSURGERY VOLUME 55 | NUMBER 6 | DECEMBER 2004 | 1377