Acta Neuropathologica

, Volume 124, Issue 5, pp 627–641 | Cite as

Disseminated oligodendroglial-like leptomeningeal tumor of childhood: a distinctive clinicopathologic entity

  • Fausto J. Rodriguez
  • Arie Perry
  • Marc K. Rosenblum
  • Sherry Krawitz
  • Kenneth J. Cohen
  • Doris Lin
  • Stacy Mosier
  • Ming-Tseh Lin
  • Charles G. Eberhart
  • Peter C. Burger
Original Paper

Abstract

Rare, generally pediatric oligodendroglioma-like neoplasms with extensive leptomeningeal dissemination have been interpreted variably as glial, oligodendroglial or glioneuronal. The clinicopathologic features have not been fully characterized. We studied 36 patients, 12 females and 24 males with a median age of 5 years (range 5 months–46 years). MRI demonstrated leptomeningeal enhancement, frequently with cystic or nodular T2 hyperintense lesions within the spinal cord/brain along the subpial surface. A discrete intraparenchymal lesion, usually in the spinal cord, was found in 25 (of 31) (81 %). Tumors contained oligodendroglioma-like cells with low-mitotic activity (median 0 per 10 high power fields, range 0–4), and rare ganglion/ganglioid cells in 6 cases (17 %). Tumors were mostly low-grade, with anaplastic progression in 8 (22 %). Immunohistochemistry demonstrated strong reactivity for OLIG2 (7 of 9) (78 %), and moderate/strong S100 (11 of 12) (92 %), GFAP (12 of 31) (39 %) and synaptophysin (19 of 27) (70 %). NeuN, EMA, and mutant IDH1 (R132H) protein were negative. Median MIB1 labeling index was 1.5 % (range <1–30 %). FISH (n = 13) or SNP array (n = 2) demonstrated 1p loss/intact 19q in 8 (53 %), 1p19q co-deletion in 3 (20 %), and no 1p or 19q loss in 4 (27 %). Clinical follow-up (n = 24) generally showed periods of stability or slow progression, but a subset of tumors progressed to anaplasia and behaved more aggressively. Nine patients (38 %) died 3 months–21 years after diagnosis (median total follow-up 5 years). We report a series of a neoplasm with distinct clinicopathologic and molecular features. Although most progress slowly, a significant fraction develop aggressive features.

Keywords

Oligodendroglioma Glioneuronal 1p 1p19q Brain Spine Leptomeninges Pediatric glioma 

Supplementary material

401_2012_1037_MOESM1_ESM.doc (88 kb)
Supplementary material 1 (DOC 88 kb)

References

  1. 1.
    Agamanolis DP, Katsetos CD, Klonk CJ, Bartkowski HM, Ganapathy S, Staugaitis SM, Kuerbitz SJ, Patton DF, Talaizadeh A, Cohen BH (2012) An unusual form of superficially disseminated glioma in children: report of 3 cases. J Child Neurol 27:727–733PubMedCrossRefGoogle Scholar
  2. 2.
    Armao DM, Stone J, Castillo M, Mitchell KM, Bouldin TW, Suzuki K (2000) Diffuse leptomeningeal oligodendrogliomatosis: radiologic/pathologic correlation. AJNR 21:1122–1126PubMedGoogle Scholar
  3. 3.
    Beck DJ, Russell DS (1942) Oligodendrogliomatosis of the cerebrospinal pathway. Brain 65:352–372CrossRefGoogle Scholar
  4. 4.
    Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH, Rodriguez FJ, Cahill DP, McLendon R, Riggins G, Velculescu VE, Oba-Shinjo SM, Marie SK, Vogelstein B, Bigner D, Yan H, Papadopoulos N, Kinzler KW (2011) Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 333:1453–1455PubMedCrossRefGoogle Scholar
  5. 5.
    Bourne TD, Mandell JW, Matsumoto JA, Jane JA Jr, Lopes MB (2006) Primary disseminated leptomeningeal oligodendroglioma with 1p deletion. Case report. J Neurosurg 105:465–469PubMedCrossRefGoogle Scholar
  6. 6.
    Capper D, Reuss D, Schittenhelm J, Hartmann C, Bremer J, Sahm F, Harter PN, Jeibmann A, von Deimling A (2011) Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology. Acta Neuropathol 121:241–252PubMedCrossRefGoogle Scholar
  7. 7.
    Chen R, Macdonald DR, Ramsay DA (1995) Primary diffuse leptomeningeal oligodendroglioma. Case report. J Neurosurg 83:724–728PubMedCrossRefGoogle Scholar
  8. 8.
    Civitello LA, Packer RJ, Rorke LB, Siegel K, Sutton LN, Schut L (1988) Leptomeningeal dissemination of low-grade gliomas in childhood. Neurology 38:562–566PubMedCrossRefGoogle Scholar
  9. 9.
    Daum S, Foncin JF, Nicolaidis S, Oeconomos D (1974) Diffuse gliomatosis of the leptomeninges and tuber oligodendrioma. Rev Neurol (Paris) 130:314–320Google Scholar
  10. 10.
    Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ (2006) Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol 7:813–820PubMedCrossRefGoogle Scholar
  11. 11.
    Gardiman MP, Fassan M, Orvieto E, D’Avella D, Denaro L, Calderone M, Severino M, Scarsello G, Viscardi E, Perilongo G (2010) Diffuse leptomeningeal glioneuronal tumors: a new entity? Brain Pathol 20:361–366PubMedCrossRefGoogle Scholar
  12. 12.
    Gilmer-Hill HS, Ellis WG, Imbesi SG, Boggan JE (2000) Spinal oligodendroglioma with gliomatosis in a child. Case report. J Neurosurg 92:109–113PubMedGoogle Scholar
  13. 13.
    Griffin CA, Burger P, Morsberger L, Yonescu R, Swierczynski S, Weingart JD, Murphy KM (2006) Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss. J Neuropathol Exp Neurol 65:988–994PubMedCrossRefGoogle Scholar
  14. 14.
    Guppy KH, Akins PT, Moes GS, Prados MD (2009) Spinal cord oligodendroglioma with 1p and 19q deletions presenting with cerebral oligodendrogliomatosis. J Neurosurg Spine 10:557–563PubMedCrossRefGoogle Scholar
  15. 15.
    Harada S, Henderson LB, Eshleman JR, Gocke CD, Burger P, Griffin CA, Batista DA (2011) Genomic changes in gliomas detected using single nucleotide polymorphism array in formalin-fixed, paraffin-embedded tissue: superior results compared with microsatellite analysis. J Mol Diagn 13:541–548PubMedCrossRefGoogle Scholar
  16. 16.
    Hervey-Jumper SL, Jumper M, Blaivas M, Parmar HA, Robertson PL, Maher CO (2010) Primary diffuse leptomeningeal oligodendroglioma. Pediatr Neurosurg 46:326–328PubMedCrossRefGoogle Scholar
  17. 17.
    Horbinski C, Miller CR, Perry A (2011) Gone FISHing: clinical lessons learned in brain tumor molecular diagnostics over the last decade. Brain Pathol 21:57–73PubMedCrossRefGoogle Scholar
  18. 18.
    Huang T, Zimmerman RA, Perilongo G, Kaufman BA, Holden KR, Carollo C, Chong WK (2001) An unusual cystic appearance of disseminated low-grade gliomas. Neuroradiology 43:868–874PubMedCrossRefGoogle Scholar
  19. 19.
    Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M, Flynn H, Passe S, Felten S, Brown PD, Shaw EG, Buckner JC (2006) A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 66:9852–9861PubMedCrossRefGoogle Scholar
  20. 20.
    Jentoft M, Giannini C, Rossi S, Mota R, Jenkins RB, Rodriguez FJ (2011) Oligodendroglial tumors with marked desmoplasia: clinicopathologic and molecular features of 7 cases. Am J Surg Pathol 35:845–852PubMedCrossRefGoogle Scholar
  21. 21.
    Jones DT, Mulholland SA, Pearson DM, Malley DS, Openshaw SW, Lambert SR, Liu L, Backlund LM, Ichimura K, Collins VP (2011) Adult grade II diffuse astrocytomas are genetically distinct from and more aggressive than their paediatric counterparts. Acta Neuropathol 121:753–761PubMedCrossRefGoogle Scholar
  22. 22.
    Korein J, Feigin I, Shapiro MF (1957) Oligodendrogliomatosis with intracranial hypertension. Neurology 7:589–594PubMedCrossRefGoogle Scholar
  23. 23.
    Kreiger PA, Okada Y, Simon S, Rorke LB, Louis DN, Golden JA (2005) Losses of chromosomes 1p and 19q are rare in pediatric oligodendrogliomas. Acta Neuropathol 109:387–392PubMedCrossRefGoogle Scholar
  24. 24.
    Ligon KL, Alberta JA, Kho AT, Weiss J, Kwaan MR, Nutt CL, Louis DN, Stiles CD, Rowitch DH (2004) The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. J Neuropathol Exp Neurol 63:499–509PubMedGoogle Scholar
  25. 25.
    Lu QR, Park JK, Noll E, Chan JA, Alberta J, Yuk D, Alzamora MG, Louis DN, Stiles CD, Rowitch DH, Black PM (2001) Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors. Proc Natl Acad Sci USA 98:10851–10856PubMedCrossRefGoogle Scholar
  26. 26.
    Lu QR, Sun T, Zhu Z, Ma N, Garcia M, Stiles CD, Rowitch DH (2002) Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109:75–86PubMedCrossRefGoogle Scholar
  27. 27.
    Mathews MS, Pare LS, Kuo JV, Kim RC (2009) Primary leptomeningeal oligodendrogliomatosis. J Neurooncol 94:275–278PubMedCrossRefGoogle Scholar
  28. 28.
    Michotte A, Chaskis C, Sadones J, Veld PI, Neyns B (2009) Primary leptomeningeal anaplastic oligodendroglioma with a 1p36-19q13 deletion: report of a unique case successfully treated with Temozolomide. J Neurol Sci 287:267–270PubMedCrossRefGoogle Scholar
  29. 29.
    Mittelbronn M, Wolff M, Bultmann E, Nagele T, Capper D, Beck R, Meyermann R, Beschorner R (2005) Disseminating anaplastic brainstem oligodendroglioma associated with allelic loss in the tumor suppressor candidate region D19S246 of chromosome 19 mimicking an inflammatory central nervous system disease in a 9-year-old boy. Hum Pathol 36:854–857PubMedCrossRefGoogle Scholar
  30. 30.
    Ng HK, Poon WS (1999) Diffuse leptomeningeal gliomatosis with oligodendroglioma. Pathology 31:59–63PubMedCrossRefGoogle Scholar
  31. 31.
    Perry A, Scheithauer BW, Macaulay RJ, Raffel C, Roth KA, Kros JM (2002) Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications. J Neuropathol Exp Neurol 61:947–955PubMedGoogle Scholar
  32. 32.
    Perry A, Burton SS, Fuller GN, Robinson CA, Palmer CA, Resch L, Bigio EH, Gujrati M, Rosenblum MK (2010) Oligodendroglial neoplasms with ganglioglioma-like maturation: a diagnostic pitfall. Acta Neuropathol 120:237–252PubMedCrossRefGoogle Scholar
  33. 33.
    Preusser M, Budka H, Rossler K, Hainfellner JA (2007) OLIG2 is a useful immunohistochemical marker in differential diagnosis of clear cell primary CNS neoplasms. Histopathology 50:365–370PubMedCrossRefGoogle Scholar
  34. 34.
    Psarros TG, Swift D, Mulne AF, Burns DK (2005) Neurocytoma-like neoplasm of the thoracic spine in a 15-month-old child presenting with diffuse leptomeningeal dissemination and communicating hydrocephalus. Case report. J Neurosurg 103:184–190PubMedGoogle Scholar
  35. 35.
    Raghavan R, Balani J, Perry A, Margraf L, Vono MB, Cai DX, Wyatt RE, Rushing EJ, Bowers DC, Hynan LS, White CL 3rd (2003) Pediatric oligodendrogliomas: a study of molecular alterations on 1p and 19q using fluorescence in situ hybridization. J Neuropathol Exp Neurol 62:530–537PubMedGoogle Scholar
  36. 36.
    Reynolds RM, Boswell E, Hulette CM, Cummings TJ, Haglund MM, Cumm Ings TJ (2011) Sudden death from diffuse leptomeningeal oligodendrogliomatosis. J Neurosurg Spine 15:625–629PubMedCrossRefGoogle Scholar
  37. 37.
    Rodriguez FJ, Mota RA, Scheithauer BW, Giannini C, Blair H, New KC, Wu KJ, Dickson DW, Jenkins RB (2009) Interphase cytogenetics for 1p19q and t(1;19)(q10;p10) may distinguish prognostically relevant subgroups in extraventricular neurocytoma. Brain Pathol 19:623–629PubMedCrossRefGoogle Scholar
  38. 38.
    Rogers LR, Estes ML, Rosenbloom SA, Harrold L (1995) Primary leptomeningeal oligodendroglioma: case report. Neurosurgery 36:166–168 discussion 169PubMedCrossRefGoogle Scholar
  39. 39.
    Roldan G, Scott J, George D, Parney I, Easaw J, Cairncross G, Forsyth P, Yan E (2008) Leptomeningeal disease from oligodendroglioma: clinical and molecular analysis. Can J Neurol Sci 35:204–209PubMedGoogle Scholar
  40. 40.
    Rossi S, Rodriguez FJ, Mota RA, Dei Tos AP, Di Paola F, Bendini M, Agostini S, Longatti P, Jenkins RB, Giannini C (2009) Primary leptomeningeal oligodendroglioma with documented progression to anaplasia and t(1;19)(q10;p10) in a child. Acta Neuropathol 118:575–577PubMedCrossRefGoogle Scholar
  41. 41.
    Senaratna S, Hanieh A, Manson J, Toogood I (2001) Multiple cystic brain lesions in a patient with pilocytic astrocytoma. J Clin Neurosci 8:363–366PubMedCrossRefGoogle Scholar
  42. 42.
    Stodberg T, Deniz Y, Esteitie N, Jacobsson B, Mousavi-Jazi M, Dahl H, Zweygberg Wirgart B, Grillner L, Linde A (2002) A case of diffuse leptomeningeal oligodendrogliomatosis associated with HHV-6 variant A. Neuropediatrics 33:266–270PubMedCrossRefGoogle Scholar
  43. 43.
    Ushida T, Sonobe H, Mizobuchi H, Toda M, Tani T, Yamamoto H (1998) Oligodendroglioma of the “widespread” type in the spinal cord. Childs Nerv Syst 14:751–755PubMedCrossRefGoogle Scholar
  44. 44.
    Utsuki S, Oka H, Kijima C, Yasui Y, Fujii K, Kawano N (2012) Pilocytic astrocytoma with abundant oligodendroglioma-like component. Brain Tumor Pathol 29:103–106PubMedCrossRefGoogle Scholar
  45. 45.
    Vasiljevic A, Francois P, Loundou A, Fevre-Montange M, Jouvet A, Roche PH, Figarella-Branger D (2012) Prognostic factors in central neurocytomas: a multicenter study of 71 cases. Am J Surg Pathol 36:220–227PubMedCrossRefGoogle Scholar
  46. 46.
    Vyberg M, Ulhoi BP, Teglbjaerg PS (2007) Neuronal features of oligodendrogliomas—an ultrastructural and immunohistochemical study. Histopathology 50:887–896PubMedCrossRefGoogle Scholar
  47. 47.
    Wakabayashi K, Shimura T, Mizutani N, Koide A, Yamagiwa O, Mori F, Nishiyama K, Tanaka R, Takahashi H (2002) Primary intracranial solitary leptomeningeal glioma: a report of 3 cases. Clin Neuropathol 21:206–213PubMedGoogle Scholar
  48. 48.
    Yamamoto T, Komori T, Shibata N, Toyoda C, Kobayashi M (1996) Multifocal neurocytoma/gangliocytoma with extensive leptomeningeal dissemination in the brain and spinal cord. Am J Surg Pathol 20:363–370PubMedCrossRefGoogle Scholar
  49. 49.
    Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J, Birol I, Chesnelong C, Chiu R, Chuah E, Corbett R, Docking R, Firme M, Hirst M, Jackman S, Karsan A, Li H, Louis DN, Maslova A, Moore R, Moradian A, Mungall KL, Perizzolo M, Qian J, Roldan G, Smith EE, Tamura-Wells J, Thiessen N, Varhol R, Weiss S, Wu W, Young S, Zhao Y, Mungall AJ, Jones SJ, Morin GB, Chan JA, Cairncross JG, Marra MA (2012) Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. J Pathol 226:7–16PubMedCrossRefGoogle Scholar
  50. 50.
    Zentner J, Anagnostopoulos J, Gilsbach J (1988) Solitary intracranial extracerebral glioma. Neurochirurgia (Stuttg) 31:101–103Google Scholar
  51. 51.
    Zhou Q, Anderson DJ (2002) The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell 109:61–73PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Fausto J. Rodriguez
    • 1
  • Arie Perry
    • 2
  • Marc K. Rosenblum
    • 3
  • Sherry Krawitz
    • 4
  • Kenneth J. Cohen
    • 5
  • Doris Lin
    • 6
  • Stacy Mosier
    • 7
  • Ming-Tseh Lin
    • 7
  • Charles G. Eberhart
    • 1
  • Peter C. Burger
    • 1
  1. 1.Department of Pathology, Division of Neuropathology, Johns Hopkins HospitalJohns Hopkins UniversityBaltimoreUSA
  2. 2.Department of PathologyUniversity of California San FranciscoSan FranciscoUSA
  3. 3.Department of PathologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Health Sciences CentreWinnipegCanada
  5. 5.The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsJohns Hopkins UniversityBaltimoreUSA
  6. 6.Division of NeuroradiologyJohns Hopkins UniversityBaltimoreUSA
  7. 7.Department of Pathology, Johns Hopkins HospitalJohns Hopkins UniversityBaltimoreUSA

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