title: Localized overexpression of alpha-internexin within nodules in multinodular and vacuolating neuronal tumors.
abstract: Multinodular and vacuolating neuronal tumors (MVNT) have been recently referred to as a distinctive neuronal tumor entity based on histopathological findings. They are characterized by multiple tumor nodules, vacuolar alteration and widespread immunolabeling for human neuronal protein HuC/HuD. Only 13 cases have been reported in the literature to date and little is known about the histopathology of these tumors. Herein, we report a case of MVNT with additional confirmation of immunohistochemical features. A 22-year-old woman presented with a continuous headache. MRI showed a subcortical white matter lesion with multiple satellite nodules in the frontal lobe appearing as T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities. Histological examination of the resected lesion revealed well-defined multiple nodules composed of predominant vacuolating tumor cells. The tumor cells exhibited consistent immunolabeling for doublecortin, as well as HuC/HuD, both representative neuronal biomarkers associated with earlier stages of neuronal development. Immunopositivity for oligodendrocyte transcription factor 2 (Olig2) and S100 was also detected in tumor cells. Additionally, significant overexpression of alpha-internexin was observed in the background neuropil limited to tumor nodules. Neuronal nuclear antigen (NeuN), synaptophysin and neurofilament, markers for mature neurons, were either negative or weakly positive. The expression profile of neuronal biomarkers can be distinguished from that of classic neuronal tumors and is the immunohistochemical hallmark of MVNT. In summary, we identified the characteristic tumoral expression of HuC/HuD and doublecortin and the presence of abundant neuropil localized in MVNT tumor nodules, which exhibited widespread alpha-internexin expression. These results supported the presumption that MVNT is a distinct histopathological entity.
authors.affiliation: Department of Neurosurgery, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya-shi, Saitama, 343-8555.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nagaishi
authors.affiliation: Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi-shi, Gunma, 371-8511, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yokoo
authors.affiliation: Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi-shi, Gunma, 371-8511, Japan.
authors.forename: Sumihito
authors.initials: S
authors.lastname: Nobusawa
authors.affiliation: Department of Neurosurgery, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya-shi, Saitama, 343-8555.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Neurosurgery, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya-shi, Saitama, 343-8555.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: Department of Neurosurgery, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya-shi, Saitama, 343-8555.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Neurosurgery, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya-shi, Saitama, 343-8555.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Neurosurgery, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya-shi, Saitama, 343-8555.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Neurosurgery, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya-shi, Saitama, 343-8555.
authors.forename: Akio
authors.initials: A
authors.lastname: Hyodo
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000473:pathology*; D000089622:Doublecortin Domain Proteins; D000067778:ELAV-Like Protein 3 / Q000032:analysis / Q000096:biosynthesis; D000067779:ELAV-Like Protein 4 / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000096:biosynthesis*; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000096:biosynthesis; D009474:Neurons / Q000473:pathology*; D009479:Neuropeptides / Q000032:analysis / Q000096:biosynthesis; D015854:Up-Regulation; D014617:Vacuoles / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000089622:Doublecortin Domain Proteins; D000067778:ELAV-Like Protein 3; D000067779:ELAV-Like Protein 4; C490264:ELAVL3 protein, human; C498010:ELAVL4 protein, human; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; C046643:alpha-internexin
keywords: HuC/HuD; ganglioglioma; internexin; multinodular; neuronal tumor