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Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study

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Abstract

Atypical choroid plexus papilloma (APP) represents a novel intermediate-grade subtype of choroid plexus tumor (CPT), the clinical outcome of which has not been described yet. We present the first analysis of a group of APP patients enrolled in the ongoing CPT-SIOP-2000 study of CPTs. A worldwide registration and a randomized trial for those patients who require chemotherapy started in 2000. For APP, maximal surgical resection was recommended. After surgery, patients who had undergone complete resection were observed, whereas patients with incompletely resected or metastasized APP were treated with six chemotherapy courses (etoposide and vincristine, combined with either carboplatin or cyclophosphamide). Risk-adapted radiotherapy was given only to patients older than 3 years of age. Of the 106 patients with a centrally confirmed CPT histology, 30 had APP, 42 CPP and 34 CPC. APP patients were significantly younger (median = 0.7 years) than patients with CPP or CPC (both medians = 2.3 years). Complete resection was achieved in 68 (64%) patients (79% in CPP, 63% in APP, and 47% in CPC). Metastases were present at diagnosis in 17% of APP patients, 5% of CPP patients, and 21% of CPC patients. All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease. In the observation group of 15 patients, one event was seen, and all patients were alive. In the treatment group, one patient with a metastasized tumor and incompletely resected APP died. While APP was defined histologically, median percentages of both the Ki-67/MIB-1 proliferation marker and the p53 tumor suppressor protein increased across the three histological subtypes (from CPP to APP and then CPC), suggesting that the subtypes comprise an ordinal categorization of increasingly severe CPT tumors. This ordering was reiterated by clinical outcome in the 92 patients treated per the study protocol, with 5-year EFS rates of 92% in 39 CPP patients, 83% in 24 APP patients, and 28% in 29 CPC patients. A similar ordering was seen when all 106 patients were evaluated for EFS. APP responded favorably to chemotherapy. The intermediate position of APP between CPP and CPC was supported by the clinical data.

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References

  1. Galassi E, Godano U, Cavallo M, Donati R, Nasi MT (1989) Intracranial tumors during the 1st year of life. Childs Nerv Syst 5:288–298

    Article  CAS  PubMed  Google Scholar 

  2. Duffner PK, Kun LE, Burger PC, Horowitz ME, Cohen ME, Sanford RA, Krischer JP, Mulhern RK, James HE, Rekate HL et al (1995) Postoperative chemotherapy and delayed radiation in infants and very young children with choroid plexus carcinomas. The Pediatric Oncology Group. Pediatr Neurosurg 22:189–196

    Article  CAS  PubMed  Google Scholar 

  3. St Clair SK, Humphreys RP, Pillay PK, Hoffman HJ, Blaser SI, Becker LE (1991) Current management of choroid plexus carcinoma in children. Pediatr Neurosurg 17:225–233

    Article  PubMed  Google Scholar 

  4. Rickert CH, Paulus W (2001) Tumors of the choroid plexus. Microsc Res Tech 52:104–111

    Article  CAS  PubMed  Google Scholar 

  5. Yadav S, Dubey AP (1993) Choroid plexus papilloma in infancy. Indian Pediatr 30:1217–1218

    CAS  PubMed  Google Scholar 

  6. Hashizume A, Kodama Y, Hotta T, Yuki K, Taniguchi E, Eguchi K, Yamasaki F, Katayama S, Yamane T, Hada Y (1995) Choroid plexus carcinoma in the lateral ventricle—case report. Neurol Med Chir (Tokyo) 35:742–744

    Article  CAS  Google Scholar 

  7. Johnson DL (1989) Management of choroid plexus tumors in children. Pediatr Neurosci 15:195–206

    Article  CAS  PubMed  Google Scholar 

  8. Laurence KM (1979) The biology of choroid plexus papilloma in infancy and childhood. Acta Neurochir (Wien) 50:79–90

    Article  CAS  Google Scholar 

  9. McGirr SJ, Ebersold MJ, Scheithauer BW, Quast LM, Shaw EG (1988) Choroid plexus papillomas: long-term follow-up results in a surgically treated series. J Neurosurg 69:843–849

    Article  CAS  PubMed  Google Scholar 

  10. Wrede B, Liu P, Ater J, Wolff JE (2005) Second surgery and the prognosis of choroid plexus carcinoma-results of a meta-analysis of individual cases. Anticancer Res 25:4429–4433

    PubMed  Google Scholar 

  11. Wrede B, Liu P, Wolff JE (2007) Chemotherapy improves the survival of patients with choroid plexus carcinoma: a meta-analysis of individual cases with choroid plexus tumors. J Neurooncol 85:345–351

    Article  PubMed  Google Scholar 

  12. Jeibmann A, Hasselblatt M, Gerss J, Wrede B, Egensperger R, Beschorner R, Hans VH, Rickert CH, Wolff JE, Paulus W (2006) Prognostic implications of atypical histologic features in choroid plexus papilloma. J Neuropathol Exp Neurol 65:1069–1073

    Article  PubMed  Google Scholar 

  13. Louis D, Ohgaki H, Wiestler O, Cavenee W, Burger P, Jouvet A, Scheithauer B, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gnekow AK (1995) Recommendations of the Brain Tumor Subcommittee for the reporting of trials. SIOP Brain Tumor Subcommittee. International Society of Pediatric Oncology. Med Pediatr Oncol 24:104–108

    Article  CAS  PubMed  Google Scholar 

  15. Hollander M, Wolfe DA (1973) Nonparametric statistical methods. Wiley, New York

    Google Scholar 

  16. Fisher RA (1922) On the interpretation of χ2 from contingency tables, and the calculation of P. J R Stat Soc 85:87–94

    Article  Google Scholar 

  17. Kaplan EL, Meier P (1958) Nonparametric estimator from incomplete observations. J Am Stat Assoc 53:457–481

    Article  Google Scholar 

  18. Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170

    CAS  PubMed  Google Scholar 

  19. Cox DR (1972) Regression models and life tables (with discussion). J R Stat Soc 34:187–220

    Google Scholar 

  20. Therneau TM (2000) Grambsch: modeling survival data. Springer, New York

    Google Scholar 

  21. Venables WN, Ripley BD (1999) Modern applied statistics with Splus. Springer, New York

    Book  Google Scholar 

  22. Valladares JB, Perry RH, Kalbag RM (1980) Malignant choroid plexus papilloma with extraneural metastasis. Case report. J Neurosurg 52:251–255

    Article  CAS  PubMed  Google Scholar 

  23. Leblanc R, Bekhor S, Melanson D, Carpenter S (1998) Diffuse craniospinal seeding from a benign fourth ventricle choroid plexus papilloma. Case report. J Neurosurg 88:757–760

    Article  CAS  PubMed  Google Scholar 

  24. Yu H, Yao TL, Spooner J, Stumph JR, Hester R, Konrad PE (2006) Delayed occurrence of multiple spinal drop metastases from a posterior fossa choroid plexus papilloma. Case report. J Neurosurg Spine 4:494–496

    Article  PubMed  Google Scholar 

  25. Uff CE, Galloway M, Bradford R (2007) Metastatic atypical choroid plexus papilloma: a case report. J Neurooncol 82:69–74

    Article  PubMed  Google Scholar 

  26. Carlotti CG Jr, Salhia B, Weitzman S, Greenberg M, Dirks PB, Mason W, Becker LE, Rutka JT (2002) Evaluation of proliferative index and cell cycle protein expression in choroid plexus tumors in children. Acta Neuropathol 103:1–10

    Article  CAS  PubMed  Google Scholar 

  27. Vajtai I, Varga Z, Aguzzi A (1996) MIB-1 immunoreactivity reveals different labelling in low-grade and in malignant epithelial neoplasms of the choroid plexus. Histopathology 29:147–151

    CAS  PubMed  Google Scholar 

  28. Soylemezoglu F, Scheithauer BW, Esteve J, Kleihues P (1997) Atypical central neurocytoma. J Neuropathol Exp Neurol 56:551–556

    Article  CAS  PubMed  Google Scholar 

  29. Brassesco MS, Valera ET, Neder L, Castro-Gamero AM, Arruda D, Machado HR, Sakamoto-Hojo ET, Tone LG (2008) Polyploidy in atypical grade II choroid plexus papilloma of the posterior fossa. Neuropathology. doi:10.1111/j.1440-1789.2008.00949.x

  30. Hasselblatt M, Bohm C, Tatenhorst L, Dinh V, Newrzella D, Keyvani K, Jeibmann A, Buerger H, Rickert CH, Paulus W (2006) Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach. Am J Surg Pathol 30:66–74

    Article  PubMed  Google Scholar 

  31. Judkins AR, Burger PC, Hamilton RL, Kleinschmidt-DeMasters B, Perry A, Pomeroy SL, Rosenblum MK, Yachnis AT, Zhou H, Rorke LB, Biegel JA (2005) INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma. J Neuropathol Exp Neurol 64:391–397

    Article  CAS  PubMed  Google Scholar 

  32. Mueller W, Eum JH, Lass U, Paulus W, Sarkar C, Bruck W, von Deimling A (2004) No evidence of hSNF5/INI1 point mutations in choroid plexus papilloma. Neuropathol Appl Neurobiol 30:304–307

    Article  CAS  PubMed  Google Scholar 

  33. Ellenbogen RG, Winston KR, Kupsky WJ (1989) Tumors of the choroid plexus in children. Neurosurgery 25:327–335

    Article  CAS  PubMed  Google Scholar 

  34. Packer RJ, Perilongo G, Johnson D, Sutton LN, Vezina G, Zimmerman RA, Ryan J, Reaman G, Schut L (1992) Choroid plexus carcinoma of childhood. Cancer 69:580–585

    Article  CAS  PubMed  Google Scholar 

  35. Pierga JY, Kalifa C, Terrier-Lacombe MJ, Habrand JL, Lemerle J (1993) Carcinoma of the choroid plexus: a pediatric experience. Med Pediatr Oncol 21:480–487

    Article  CAS  PubMed  Google Scholar 

  36. Pencalet P, Sainte-Rose C, Lellouch-Tubiana A, Kalifa C, Brunelle F, Sgouros S, Meyer P, Cinalli G, Zerah M, Pierre-Kahn A, Renier D (1998) Papillomas and carcinomas of the choroid plexus in children. J Neurosurg 88:521–528

    Article  CAS  PubMed  Google Scholar 

  37. McEvoy AW, Harding BN, Phipps KP, Ellison DW, Elsmore AJ, Thompson D, Harkness W, Hayward RD (2000) Management of choroid plexus tumours in children: 20 years experience at a single neurosurgical centre. Pediatr Neurosurg 32:192–199

    Article  CAS  PubMed  Google Scholar 

  38. Wolff JE, Sajedi M, Brant R, Coppes MJ, Egeler RM (2002) Choroid plexus tumours. Br J Cancer 87:1086–1091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Krishnan S, Brown PD, Scheithauer BW, Ebersold MJ, Hammack JE, Buckner JC (2004) Choroid plexus papillomas: a single institutional experience. J Neurooncol 68:49–55

    Article  PubMed  Google Scholar 

  40. Jeibmann A, Wrede B, Peters O, Wolff JE, Paulus W, Hasselblatt M (2007) Malignant progression in choroid plexus papillomas. J Neurosurg 107:199–202

    PubMed  Google Scholar 

  41. Shintaku M, Nitta T, Matsubayashi K, Okamoto S (2008) Ossifying choroid plexus papilloma recurring with features of atypical papilloma. Neuropathology 28:160–164

    Article  PubMed  Google Scholar 

  42. Berger C, Thiesse P, Lellouch-Tubiana A, Kalifa C, Pierre-Kahn A, Bouffet E (1998) Choroid plexus carcinomas in childhood: clinical features and prognostic factors. Neurosurgery 42:470–475

    Article  CAS  PubMed  Google Scholar 

  43. Chow E, Jenkins JJ, Burger PC, Reardon DA, Langston JW, Sanford RA, Heideman RL, Kun LE, Merchant TE (1999) Malignant evolution of choroid plexus papilloma. Pediatr Neurosurg 31:127–130

    Article  CAS  PubMed  Google Scholar 

  44. Maria BL, Graham ML, Strauss LC, Wharam MD (1985) Response of a recurrent choroid plexus tumor to combination chemotherapy. J Neurooncol 3:259–262

    Article  CAS  PubMed  Google Scholar 

  45. Valencak J, Dietrich W, Raderer M, Dieckmann K, Prayer D, Hainfellner JA, Marosi C (2000) Evidence of therapeutic efficacy of CCNU in recurrent choroid plexus papilloma. J Neurooncol 49:263–268

    Article  CAS  PubMed  Google Scholar 

  46. Pillai A, Rajeev K, Chandi S, Unnikrishnan M (2004) Intrinsic brainstem choroid plexus papilloma. Case report. J Neurosurg 100:1076–1078

    Article  PubMed  Google Scholar 

  47. Tacconi L, Delfini R, Cantore G (1996) Choroid plexus papillomas: consideration of a surgical series of 33 cases. Acta Neurochir (Wien) 138:802–810

    Article  CAS  Google Scholar 

  48. Wolff JE, Sajedi M, Coppes MJ, Anderson RA, Egeler RM (1999) Radiation therapy and survival in choroid plexus carcinoma. Lancet 353:2126

    Article  CAS  PubMed  Google Scholar 

  49. Enomoto H, Mizuno M, Katsumata T, Doi T (1991) Intracranial metastasis of a choroid plexus papilloma originating in the cerebellopontine angle region: a case report. Surg Neurol 36:54–58

    Article  CAS  PubMed  Google Scholar 

  50. McEvoy AW, Galloway M, Revesz T, Kitchen ND (2002) Metastatic choroid plexus papilloma: a case report. J Neurooncol 56:241–246

    Article  PubMed  Google Scholar 

  51. Ortega-Martinez M, Cabezudo-Artero JM, Fernandez-Portales I, Pimentel JJ, Gomez de Tejada R (2007) Diffuse leptomeningeal seeding from benign choroid plexus papilloma. Acta Neurochir (Wien) 149:1229–1236 (discussion 1236-1227)

    Article  CAS  Google Scholar 

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Acknowledgements

The CPT-SIOP-2000 study was designed in 1999, and far more people had significantly more academic impact during the past decade than suggested by the list of authors. We thank David Ellison (Pathology, Memphis, TN, USA) for excellent neuropathology work and helpful scientific discussion. We thank Richard Sposto (Children’s Hospital of Los Angeles, USA) for statistical support and enthusiasm to get the study. Among the numerous clinical participants, we wish to thank R. Corbett, M. Nathrath, S. Van Gool, L. Leskova, G. Ebetsberger, J. Sterba, N. Jorch, D. Ashley, B. Erdlenbruch, C. Kramm, J. Finlay, M. Warmuth Metz, R. Kebudi, T. Hassall, M. Dittrich, N. Konoplya, M. v. d. Hagen, I. Slavc, U. Kontny, M. Albert, R. Reddingius, D. C. Kiss, A. Navajos, M. L. Garre, and many others. The CPT-SIOP-2000 study is supported by the Deutsche Kinderkrebsstiftung, also supporting B. W. M. H. and W. P. are supported by Deutsche Krebshilfe (Grant 108263).

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Authors and Affiliations

  1. Department of Pediatric Oncology, St. Hedwig Children’s Hospital, University of Regensburg, Regensburg, Germany

    Brigitte Wrede, Ove Peters & Johannes E. A. Wolff

  2. Institute of Neuropathology, University Hospital Münster, Münster, Germany

    Martin Hasselblatt, Werner Paulus & Astrid Jeibmann

  3. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Peter F. Thall, Xuemei Wang & Johannes E. A. Wolff

  4. Institute of Oncology, Hacettepe University, Ankara, Turkey

    Tezer Kutluk

  5. Department of Pediatrics, Sainte-Justine Hospital, Montreal, Canada

    Albert Moghrabi

  6. Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Anita Mahajan

  7. Department of Pediatric Hematology and Oncology, University of Hamburg-Eppendorf, Hamburg, Germany

    Stefan Rutkowski

  8. Neuro Oncology Program, Institute of Neurological Research, FLENI, Buenos Aires, Argentina

    Blanca Diez

  9. Institute for Neuropathology, University of Bonn, Bonn, Germany

    Torsten Pietsch

  10. Department of Radiotherapy, University of Leipzig, Leipzig, Germany

    Rolf-Dieter Kortmann

  11. Department of Pediatrics, Unit 87, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Johannes E. A. Wolff

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  1. Brigitte Wrede
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  15. Johannes E. A. Wolff
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Correspondence to Johannes E. A. Wolff.

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Wrede, B., Hasselblatt, M., Peters, O. et al. Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study. J Neurooncol 95, 383–392 (2009). https://doi.org/10.1007/s11060-009-9936-y

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