Abstract
Purpose
Papillary glioneuronal tumors (PGNT) have been recently included as a distinct entity in the WHO classification of tumors of the central nervous system. Their molecular pathogenesis is not clear. In the current study, we present the morphological, immunohistochemical, and molecular features of four cases of PGNT reported over the past 11 years.
Methods
Over a period of 11 years (January 2000–February 2010), there were four cases of PGNT, which were reviewed for histomorphological features. TP53 and IDH1 mutations were assessed using antibodies against p53 protein and for mutant IDH1R132H protein, respectively. Immunohistochemistry was also performed for epidermal growth factor receptor (EGFR) protein. Fluorescence in situ hybridization assay was used for analyzing 1p/19q deletion status.
Results
All the tumors showed the characteristic biphasic morphology. Rare findings included minigemistocyte-like cells in one, angiomatous areas in three, focal necrosis in one, and a high MIB-1 labeling index of 12 and 13 %, respectively, in two of the cases. All lacked EGFR, IDH1 expression, and 1p/19q deletions. Interestingly, antibody for p53 labeled the tumor cells, mainly those showing glial differentiation, in two cases. At a mean follow-up of 30 months, there was no evidence of disease progression except in one case which recurred after 24 months.
Conclusion
PGNT are rare CNS neoplasms. Despite showing focal morphological features reminiscent of oligodendroglial tumors and presence of astrocytic component, they usually lack the common genetic alterations involved in the pathogenesis of gliomas. Multi-institutional pooling of cases may aid in elucidating their oncogenetic pathway.
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References
Nakazato Y, Figarella-Branger D, Becker AJ, Scheithauer BW, Rosenblum MK (2007) Papillary glioneuronal tumor. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system, 4th edn. IARC Press, Lyon, pp 113–114
Nelson JS, Bruner JM, Weistler OD, VandenBerg SR (2000) Ganglioglioma and gangliocytoma. In: Kleihues P, Cavenee WK (eds) World Health Organization classification of tumours. Pathology and genetic of tumours of the nervous system, 3rd edn. IARC Press, Lyon, p 97
Komori T, Scheithauer BW, Anthony DC, Scott RM, Okazaki H, Kobayashi M (1996) Pseudopapillary ganglioneurocytoma. J Neuropathol Exp Neurol 55:654
Kim DH, Suh YL (1997) Pseudopapillary neurocytoma of temporal lobe with glial differentiation. Acta Neuropathol 94:187–191
Komori T, Scheithauer BW, Anthony DC, Rosenblum MK, McLendon RE, Scott RM, Okazaki H, Kobayashi M (1998) Papillary glioneuronal tumor: a new variant of mixed neuronal-glial neoplasm. Am J Surg Pathol 22:1171–1183
Bouvier-Labit C, Daniel L, Dufour H, Grisoli F, Figarella-Branger D (2000) Papillary glioneuronal tumour: clinicopathological and biochemical study of one case with 7-year follow up. Acta Neuropathol 99:321–326
Prayson RA (2000) Papillary glioneuronal tumor. Arch Pathol Lab Med 124:1820–1823
Barnes NP, Pollock JR, Harding B, Hayward RD (2002) Papillary glioneuronal tumour in a 4-year-old. Pediatr Neurosurg 36:266–270
Broholm H, Madsen FF, Wagner AA, Laursen H (2002) Papillary glioneuronal tumor—a new tumor entity. Clin Neuropathol 21:1–4
Tsukayama C, Arakawa Y (2002) A papillary glioneuronal tumor arising in an elderly woman: a case report. Brain Tumor Pathol 19:35–39
Ebato M, Tsunoda A, Maruki C, Ikeya F, Okada M (2003) Papillary glioneuronal tumor with highly degenerative pseudopapillary structure accompanied by specific abortive glial cells: a case report. No Shinkei Geka 31:1185–1190
Kordek R, Hennig R, Jacobsen E, Kearney M (2003) Papillary glioneuronal tumor—a new variant of benign mixed brain neoplasm. Pol J Pathol 54:75–78
Lamszus K, Makrigeorgi-Butera M, Laas R, Westphal M, Stavrou D (2003) September 2002: 24-year-old female with a 6-month history of seizures. Brain Pathol 13:115–117
Borges G, Bonilha L, Menezes AS, Queiroz Lde S, Carelli EF, Zanardi V, Menezes JR (2004) Long term follow-up in a patient with papillary glioneuronal tumor. Arq Neuropsiquiatr 62:869–872
Stosic-Opincal T, Peric V, Gavrilovic S, Gavrilov M, Markovic Z, Sener RN (2005) Papillary glioneuronal tumor. AJR Am J Roentgenol 185:265–267
Tanaka Y, Yokoo H, Komori T, Makita Y, Ishizawa T, Hirose T, Ebato M, Shibahara J, Tsukayama C, Shibuya M, Nakazato Y (2005) A distinct pattern of Olig2-positive cellular distribution in papillary glioneuronal tumors: a manifestation of the oligodendroglial phenotype? Acta Neuropathol 110:39–47
Chen L, Piao YS, Xu QZ, Yang XP, Yang H, Lu DH (2006) Papillary glioneuronal tumor: a clinicopathological and immunohistochemical study of two cases. Neuropathology 26:243–248
Buccoliero AM, Giordano F, Mussa F, Taddei A, Genitori L, Taddei GL (2006) Papillary glioneuronal tumor radiologically mimicking a cavernous hemangioma with hemorrhagic onset. Neuropathology 26:206–211
Celli P, Caroli E, Giangaspero F, Ferrante L (2006) Papillary glioneuronal tumor. Case report and literature review. J Neurooncol 80:185–189
Dim DC, Lingamfelter DC, Taboada EM, Fiorella RM (2006) Papillary glioneuronal tumor: a case report and review of the literature. Hum Pathol 37:914–918
Epelbaum S, Kujas M, Van Effenterre R, Poirier J (2006) Two cases of papillary glioneuronal tumours. Br J Neurosurg 20:90–93
Ishizawa T, Komori T, Shibahara J, Ishizawa K, Adachi J, Nishikawa R, Matsutani M, Hirose T (2006) Papillary glioneuronal tumor with minigemistocytic components and increased proliferative activity. Hum Pathol 37:627–630
Konya D, Peker S, Ozgen S, Kurtkaya O, Necmettin Pamir M (2006) Superficial siderosis due to papillary glioneuronal tumor. J Clin Neurosci 13:950–952
Qi JP, Zhu H, Li DY, Mei HL (2006) Papillary glioneuronal tumor: report of a case. Zhonghua Bing Li Xue Za Zhi 35:764–765, Chinese
Vajtai I, Kappeler A, Lukes A, Arnold M, Lüthy AR, Leibundgut K (2006) Papillary glioneuronal tumor. Pathol Res Pract 202:107–112
Adam C, Polivka M, Carpentier A, George B, Gray F (2007) Papillary glioneuronal tumor: not always a benign tumor? Clin Neuropathol 26:119–124
Atri S, Sharma MC, Sarkar C, Garg A, Suri A (2007) Papillary glioneuronal tumour: a report of a rare case and review of literature. Childs Nerv Syst 23:349–353
Gelpi E, Preusser M, Czech T, Slavc I, Prayer D, Budka H (2007) Papillary glioneuronal tumor. Neuropathology 27:468–473
Radotra BD, Kumar Y, Bhatia A, Mohindra S (2007) Papillary glioneuronal tumor: a new entity awaiting inclusion in WHO classification. Diagn Pathol 2:6–10
Vaquero J, Coca S (2007) Atypical papillary glioneuronal tumor. J Neurooncol 83:319–323
Faria C, Miguéns J, Antunes JL, Barroso C, Pimentel J, Martins Mdo C, Moura-Nunes V, Roque L (2008) Genetic alterations in a papillary glioneuronal tumor. J Neurosurg Pediatr 1:99–102
Guo SP, Zhang F, Li QL, Li Q, Wang WL, Li FF (2008) Papillary glioneuronal tumor—contribution to a new tumor entity and literature review. Clin Neuropathol 27:72–77
Izycka-Swieszewska E, Majewska H, Szurowska E, Mazurkiewicz-Bełdzińska M, Drozyńska E (2008) Papillary glioneuronal tumour of the precentral gyrus. Folia Neuropathol 46:158–163
Newton HB, Dalton J, Ray-Chaudhury A, Gahbauer R, McGregor J (2008) Aggressive papillary glioneuronal tumor: case report and literature review. Clin Neuropathol 27:317–324
Williams SR, Joos BW, Parker JC, Parker JR (2008) Papillary glioneuronal tumor: a case report and review of the literature. Ann Clin Lab Sci 38:287–292
Govindan A, Mahadevan A, Bhat DI, Arivazhagan A, Chakraborti S, Suja MS, Phalguni AA, Sampath S, Chandramouli BA, Shankar SK (2009) Papillary glioneuronal tumor-evidence of stem cell origin with biphenotypic differentiation. J Neurooncol 95:71–80
Javahery RJ, Davidson L, Fangusaro J, Finlay JL, Gonzalez-Gomez I, McComb JG (2009) Aggressive variant of a papillary glioneuronal tumor. Report of 2 cases. J Neurosurg Pediatr 3:46–52
Pimentel J, Barroso C, Miguéns J, Firmo C, Antunes JL (2009) Papillary glioneuronal tumor—prognostic value of the extension of surgical resection. Clin Neuropathol 28:287–294
Mahajan H, Varikatt W, Dexter M, Boadle R, Ng T (2010) Papillary glioneuronal tumor of the frontal lobe. J Clin Neurosci 17:534–536
Phi JH, Park SH, Chae JH, Wang KC, Cho BK, Kim SK (2010) Papillary glioneuronal tumor present in a patient with encephalocraniocutaneous lipomatosis: case report. Neurosurgery 67:E1165–E1169
Xiao H, Ma L, Lou X, Gui Q (2011) Papillary glioneuronal tumor: radiological evidence of a newly established tumor entity. J Neuroimaging 21:297–302
Myung JK, Byeon SJ, Kim B, Suh J, Kim SK, Park CK, Chung CK, Chang KH, Park SH (2011) Papillary glioneuronal tumors: a review of clinicopathologic and molecular genetic studies. Am J Surg Pathol 35:1794–1805
Squire JA, Arab S, Marrano P, Bayani J, Karaskova J, Taylor M, Becker L, Rutka J, Zielenska M (2001) Molecular cytogenetic analysis of glial tumors using spectral karyotyping and comparative genomic hybridization. Mol Diagn 6:93–108
Horstmann S, Perry A, Reifenberger G, Giangaspero F, Huang H, Hara A, Masuoka J, Rainov NG, Bergmann M, Heppner FL, Brandner S, Chimelli L, Montagna N, Jackson T, Davis DG, Markesbery WR, Ellison DW, Weller RO, Taddei GL, Conti R, Del Bigio MR, González-Cámpora R, Radhakrishnan VV, Söylemezoglu F, Uro-Coste E, Qian J, Kleihues P, Ohgaki H (2004) Genetic and expression profiles of cerebellar liponeurocytomas. Brain Pathol 14:281–289
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812
Horbinski C, Kofler J, Kelly LM, Murdoch GH, Nikiforova MN (2009) Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. J Neuropathol Exp Neurol 68:1319–1325
Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773
Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, Felsberg J, Wolter M, Mawrin C, Wick W, Weller M, Herold-Mende C, Unterberg A, Jeuken JW, Wesseling P, Reifenberger G, von Deimling A (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118:469–474
Ichimura K, Pearson DM, Kocialkowski S, Bäcklund LM, Chan R, Jones DT, Collins VP (2009) IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro Oncol 11:341–347
Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A (2009) Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 118:599–601
Camelo-Piragua S, Jansen M, Ganguly A, Kim JC, Louis DN, Nutt CL (2010) Mutant IDH1-specific immunohistochemistry distinguishes diffuse astrocytoma from astrocytosis. Acta Neuropathol 119:509–511
Sanson M, Marie Y, Paris S et al (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154
Bleeker FE, Atai NA, Lamba S, Jonker A, Rijkeboer D, Bosch KS, Tigchelaar W, Troost D, Vandertop WP, Bardelli A, Van Noorden CJ (2010) The prognostic IDH1 (R132) mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma. Acta Neuropathol 119:487–494
Agarwal S, Sharma MC, Sarkar C, Suri V, Jain A, Sharma MS, Ailawadhi P, Garg A, Mallick S (2011) Extraventricular neurocytomas: a morphological and histogenetic consideration. A study of six cases. Pathology 43:327–334
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Agarwal, S., Sharma, M.C., Singh, G. et al. Papillary glioneuronal tumor—a rare entity: report of four cases and brief review of literature. Childs Nerv Syst 28, 1897–1904 (2012). https://doi.org/10.1007/s00381-012-1860-3
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DOI: https://doi.org/10.1007/s00381-012-1860-3