Well-Differentiated Pediatric Glial Neoplasms with Features of Oligodendroglioma, Angiocentric Glioma and Dysembryoplastic Neuroepithelial Tumors: A Morphological Diagnostic Challenge / Oligodendrogliom, Anjiosentrik Gliom ve Disembriyoplastik Nöroepitelyal Tümör Özellikleri Taşıyan İyi Diferansiye Pediatrik Glial Tümörler: Morfolojik Bir Tanısal Sorun
Objective: Oligodendrogliomas are rare in the pediatric population, and most oligodendroglioma-like tumors in this age group may belong to other entities. In addition, accurate diagnosis and grading of such lesions using criteria developed for adult oligodendrogliomas prove difficult, and often controversial. Material and Method: During a study of tumors previously diagnosed as pediatric oligodendroglioma, we identified four tumors displayed features of that resembled oligodendroglioma, angiocentric glioma and dysembryoplastic neuroepithelial tumor but could not be classified as either one of these entities. Ther clinical, histological and immunohistochemical features of these cases were investigated in this study. Results: Two male (both 9 years old) and two female (ages 4 years and 20 months) patients presented with new onset of seizures. All patients were treated surgically, and two required reoperation. Histologically, the tumors were well-differentiated glial neoplasms with focal angiocentric pattern, delicate vascularity, diffuse growth, infiltrative margins, cortical nodules, focal myxoid areas, and leptomeningeal extension. Immunohistochemical studies showed diffuse nuclear positivity with Olig-2 and GFAP antibodies, whereas staining with neuronal markers, EMA, p53, and IDH1 were negative. Fluorescent in-situ hybridization analysis demonstrated intact 1p/19q in all tumors, and there was no ultrastructural evidence of ependymal differentiation. All patients were alive with disease with a mean follow-up of 112 months. Conclusion: These four cases illustrate the morphological diversity of well-differentiated, oligodendroglioma-like glial neoplasms and the uncertainty in their classification among pediatric tumors.
1. Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol. 2012; Suppl 5:v1-49.
2. R aghavan R, Balani J, Perry A, Margraf L, Vono MB, Cai DX, Wyatt RE, Rushing EJ, Bowers DC, Hynan LS, White CL 3rd. Pediatric oligodendrogliomas: A study of molecular alterations on 1p and 19q using fluorescence in situ hybridization. J Neuropathol Exp Neurol. 2003; 62:530-7.
3. McDonald WC, Nigro JM, Lin D, Jenkins RB, Feuerstein BG, Burger C, Tihan T. Glial neoplasm resembling oligodendrogliomas in children: Does pediatric oligodendroglioma exist? Glioma marker network study. J Neuropathol Exp Neurol. 2003; 65:571 (Abstract).
4. Kreiger PA, Okada Y, Simon S, Rorke LB, Louis DN, Golden JA. Losses of chromosomes 1p and 19q are rare in pediatric oligodendrogliomas. Acta Neuropathol. 2005; 109: 387-92.
5. Preusser M, Hoischen A, Novak K, Czech T, Prayer D, Hainfellner JA, Baumgartner C, Woermann FG, Tuxhorn IE, Pannek HW, Bergmann M, Radlwimmer B, Villagrán R, Weber RG, Hans VH.Angiocentric glioma: Report of clinico-pathologic and genetic findings in 8 cases. Am J Surg Pathol. 2007; 31:1709-18.
6. Wang M, Tihan T, Rojiani AM, Bodhireddy SR, Prayson RA , Iacuone JJ, Alles AJ, Donahue DJ, Hessler RB, Kim JH, Haas M, Rosenblum MK, Burger PC. Monomorphous angiocentric glioma: a distinctive epileptogenic neoplasm with features of infiltrating astrocytoma and ependymoma. J Neuropathol Exp Neurol. 2005; 64:875-81.
7. Fuller GN. The WHO Classification of Tumours of the Central Nervous System, 4th edition. Arch Pathol Lab Med. 2008;132:906
8. Marburger T, Prayson R. Angiocentric glioma: A clinicopathologic review of 5 tumors with identification of associated cortical dysplasia. Arch Pathol Lab Med. 2011; 135:1037-41.
9. Lellouch-Tubiana A, Boddaert N, Bourgeois M, Fohlen M, Jouvet A, Delalande O, Seidenwurm D, Brunelle F, Sainte-Rose C. Angiocentric neuroepithelial tumor (ANET): A new epilepsyrelated clinicopathological entity with distinctive MRI. Brain Pathol. 2005; 15:281-6.
10. Geha S, Pallud J, Junier MP, Devaux B, Leonard N, Chassoux F, Chneiweiss H, Daumas-Duport C, Varlet P. NG2+/Olig2+ cells are the major cycle-related cell population of the adult human normal brain. Brain Pathol. 2010; 20:399-411.
11. Baisden BL, Brat DJ, Melhem ER, Rosenblum MK, King AP, Burger PC. Dysembryoplastic neuroepithelial tumor-like neoplasm of the septum pellucidum: A lesion often misdiagnosed as glioma: Report of 10 cases. Am J Surg Pathol. 2001; 25:494-9.
12. Dimou L, Simon C, Kirchhoff F, Takebayashi H, Götz M. Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex. J Neurosci. 2008; 28:10434-42.
13. Burger PC. What is an oligodendroglioma? Brain Pathol. 2002; 12:257-9.
14. Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW; St. Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nature Genetics. 2013; 45:602-12.