Journal of Neuro-Oncology

, Volume 96, Issue 2, pp 143–149 | Cite as

Management of primary intracranial germ cell tumors

  • Athanassios P. Kyritsis
Topic Review


Primary intracranial germ cell tumors are rare and usually localized in the pineal and the suprasellar regions. They are divided into the following histologic types: germinoma, teratoma (mature, immature, malignant), choriocarcinoma, embryonal carcinoma, endodermal sinus tumor (yolk sac tumor), and mixed tumors. Clinically, they are manifested with ocular signs or signs of obstructive hydrocephalus. Localized germinomas are treated with radiation therapy and exhibit a relatively good prognosis. Chemotherapy is reserved for disseminated germinomas. Mature teratomas are treated with surgery. The rest of germ cell tumors are managed with various combinations of surgery, chemotherapy, and radiotherapy depending on the tumor type. If the tumors secrete beta-human chorionic gonadotrophin (hCG) or alpha-fetoprotein (FP), these tumor markers can be used to accurately monitor response to treatment. Prognosis is best for germinomas and mature teratomas and worst for choriocarcinomas and embryonal carcinomas.


Choriocarcinoma Embryonal carcinoma Germ cell tumor Germinoma Teratoma 


  1. 1.
    Levin VA, Giglio P, Kyritsis AP (2005) The management of gliomas, medulloblastoma, CNS germ cell tumors, and carcinomas metastatic to the CNS. In: Cavalli F, Hansen H, Kaye S (eds) Textbook of medical oncology. Martin Dunitz, London, England, pp 415–430Google Scholar
  2. 2.
    Jennings MT, Gelman R, Hochberg F (1985) Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg 63:155–167CrossRefPubMedGoogle Scholar
  3. 3.
    Liang L, Korogi Y, Sugahara T, Ikushima I, Shigematsu Y, Okuda T, Takahashi M, Kochi M, Ushio Y (2002) MRI of intracranial germ-cell tumours. Neuroradiology 44:382–388CrossRefPubMedGoogle Scholar
  4. 4.
    Smirniotopoulos JG, Rushing EJ, Mena H (1992) Pineal region masses: differential diagnosis. Radiographics 12:577–596PubMedGoogle Scholar
  5. 5.
    Kyritsis A (1998) Evaluation and treatment of CNS neoplasms. In: Lechtenberg R, Schutta HS (eds) Neurology practice guidelines. Marcel Dekker, New York, pp 473–496Google Scholar
  6. 6.
    Okada Y, Nishikawa R, Matsutani M, Louis DN (2002) Hypomethylated X chromosome gain and rare isochromosome 12p in diverse intracranial germ cell tumors. J Neuropathol Exp Neurol 61:531–538PubMedGoogle Scholar
  7. 7.
    Juric D, Sale S, Hromas RA, Yu R, Wang Y, Duran GE, Tibshirani R, Einhorn LH, Sikic BI (2005) Gene expression profiling differentiates germ cell tumors from other cancers and defines subtype-specific signatures. Proc Natl Acad Sci USA 102:17763–17768CrossRefPubMedGoogle Scholar
  8. 8.
    Losi L, Polito P, Hagemeijer A, Buonamici L, Van den BH, Dal CP (1998) Intracranial germ cell tumour (embryonal carcinoma with teratoma) with complex karyotype including isochromosome 12p. Virchows Arch 433:571–574CrossRefPubMedGoogle Scholar
  9. 9.
    Asanoma K, Matsuda T, Kondo H, Kato K, Kishino T, Niikawa N, Wake N, Kato H (2003) NECC1, a candidate choriocarcinoma suppressor gene that encodes a homeodomain consensus motif. Genomics 81:15–25CrossRefPubMedGoogle Scholar
  10. 10.
    Miyanohara O, Takeshima H, Kaji M, Hirano H, Sawamura Y, Kochi M, Kuratsu J (2002) Diagnostic significance of soluble c-kit in the cerebrospinal fluid of patients with germ cell tumors. J Neurosurg 97:177–183CrossRefPubMedGoogle Scholar
  11. 11.
    Nishikawa R, Matsutani M (1998) Immunohistochemical analysis of p53 and p21(WAF1/Cip1) expression in primary intracranial germ cell tumors. Neurosurg Focus 5:e2CrossRefPubMedGoogle Scholar
  12. 12.
    Yamagami T, Handa H, Yamashita J, Okumura T, Paine J, Haebara H, Furukawa F (1987) An immunohistochemical study of intracranial germ cell tumours. Acta Neurochir (Wien) 86:33–41CrossRefGoogle Scholar
  13. 13.
    Hirato J, Nakazato Y (2001) Pathology of pineal region tumors. J Neurooncol 54:239–249CrossRefPubMedGoogle Scholar
  14. 14.
    Sano K (1999) Pathogenesis of intracranial germ cell tumors reconsidered. J Neurosurg 90:258–264CrossRefPubMedGoogle Scholar
  15. 15.
    Chang T, Teng MM, Guo WY, Sheng WC (1989) CT of pineal tumors and intracranial germ-cell tumors. AJR Am J Roentgenol 153:1269–1274PubMedGoogle Scholar
  16. 16.
    Konovalov AN, Pitskhelauri DI (2003) Principles of treatment of the pineal region tumors K2003. Surg Neurol 59:250–268CrossRefPubMedGoogle Scholar
  17. 17.
    Fujimaki T, Matsutani M, Funada N, Kirino T, Takakura K, Nakamura O, Tamura A, Sano K (1994) CT and MRI features of intracranial germ cell tumors. J Neurooncol 19:217–226CrossRefPubMedGoogle Scholar
  18. 18.
    Tien RD, Barkovich AJ, Edwards MS (1990) MR imaging of pineal tumors. AJR Am J Roentgenol 155:143–151PubMedGoogle Scholar
  19. 19.
    Chang IB, Cho BM, Park SH, Yoon DY, Oh SM (2008) Metastatic choriocarcinoma with multiple neoplastic intracranial microaneurysms: case report. J Neurosurg 108:1014–1017CrossRefPubMedGoogle Scholar
  20. 20.
    Huang CY, Chen CA, Hsieh CY, Cheng WF (2007) Intracerebral hemorrhage as initial presentation of gestational choriocarcinoma: a case report and literature review. Int J Gynecol Cancer 17:1166–1171PubMedCrossRefGoogle Scholar
  21. 21.
    Vaquero J, Martinez R, Manrique M (2000) Stereotactic biopsy for brain tumors: is it always necessary? Surg Neurol 53:432–437CrossRefPubMedGoogle Scholar
  22. 22.
    Shinoda J, Sakai N, Yano H, Hattori T, Ohkuma A, Sakaguchi H (2004) Prognostic factors and therapeutic problems of primary intracranial choriocarcinoma/germ-cell tumors with high levels of HCG. J Neurooncol 66:225–240CrossRefPubMedGoogle Scholar
  23. 23.
    Blakeley JO, Grossman SA (2006) Management of pineal region tumors. Curr Treat Options Oncol 7:505–516CrossRefPubMedGoogle Scholar
  24. 24.
    Haas-Kogan DA, Missett BT, Wara WM, Donaldson SS, Lamborn KR, Prados MD, Fisher PG, Huhn SL, Fisch BM, Berger MS, Le QT (2003) Radiation therapy for intracranial germ cell tumors. Int J Radiat Oncol Biol Phys 56:511–518CrossRefPubMedGoogle Scholar
  25. 25.
    Franzini A, Leocata F, Servello D, Cajola L, Allegranza A, Broggi G (1998) Long-term follow-up of germinoma after stereotactic biopsy and brain radiotherapy: a cell kinetics study. J Neurol 245:593–597CrossRefPubMedGoogle Scholar
  26. 26.
    Wolden SL, Wara WM, Larson DA, Prados MD, Edwards MS, Sneed PK (1995) Radiation therapy for primary intracranial germ-cell tumors. Int J Radiat Oncol Biol Phys 32:943–949PubMedGoogle Scholar
  27. 27.
    Matsutani M (2004) Clinical management of primary central nervous system germ cell tumors. Semin Oncol 31:676–683CrossRefPubMedGoogle Scholar
  28. 28.
    Echevarria ME, Fangusaro J, Goldman S (2008) Pediatric central nervous system germ cell tumors: a review. Oncologist 13:690–699CrossRefPubMedGoogle Scholar
  29. 29.
    Bilgin T, Ozan H, Ozuysal S, Ozkan L (2004) Successful salvage therapy of resistant gestational trophoblastic disease with etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP). Arch Gynecol Obstet 269:159–160CrossRefPubMedGoogle Scholar
  30. 30.
    Chen LP, Cai SM, Fan JX, Li ZT (1995) PEBA regimen (cisplatin, etoposide, bleomycin, and adriamycin) in the treatment of drug-resistant choriocarcinoma. Gynecol Oncol 56:231–234CrossRefPubMedGoogle Scholar
  31. 31.
    Rustin GJ, Newlands ES, Begent RH, Dent J, Bagshawe KD (1989) Weekly alternating etoposide, methotrexate, and actinomycin/vincristine and cyclophosphamide chemotherapy for the treatment of CNS metastases of choriocarcinoma. J Clin Oncol 7:900–903PubMedGoogle Scholar
  32. 32.
    Termrungruanglert W, Kudelka AP, Piamsomboon S, Verschraegen CF, Edwards CL, Lifshitz S, Mante RP, Kavanagh JJ (1996) Remission of refractory gestational trophoblastic disease with high-dose paclitaxel. Anticancer Drugs 7:503–506CrossRefPubMedGoogle Scholar
  33. 33.
    Friedman JA, Lynch JJ, Buckner JC, Scheithauer BW, Raffel C (2001) Management of malignant pineal germ cell tumors with residual mature teratoma. Neurosurgery 48:518–522CrossRefPubMedGoogle Scholar
  34. 34.
    Kohyama S, Uematsu M, Ishihara S, Shima K, Tamai S, Kusano S (2001) An experience of stereotactic radiation therapy for primary intracranial choriocarcinoma. Tumori 87:162–165PubMedGoogle Scholar
  35. 35.
    Brandes AA, Pasetto LM, Monfardini S (2000) The treatment of cranial germ cell tumours. Cancer Treat Rev 26:233–242CrossRefPubMedGoogle Scholar
  36. 36.
    Akai T, Iizuka H, Kadoya S, Nojima T (1998) Extraneural metastasis of intracranial germinoma with syncytiotrophoblastic giant cells—case report. Neurol Med Chir (Tokyo) 38:574–577CrossRefGoogle Scholar
  37. 37.
    Sievers EL, Berger M, Geyer JR (1996) Long-term survival of a patient with primary sellar choriocarcinoma with pulmonary metastases: a case report. Med Pediatr Oncol 26:293–295CrossRefPubMedGoogle Scholar
  38. 38.
    Kageji T, Nagahiro S, Matsuzaki K, Kanematsu Y, Nakatani M, Okamoto Y, Watanabe T (2007) Successful neoadjuvant synchronous chemo- and radiotherapy for disseminated primary intracranial choriocarcinoma: case report. J Neurooncol 83:199–204CrossRefPubMedGoogle Scholar
  39. 39.
    Kochi M, Itoyama Y, Shiraishi S, Kitamura I, Marubayashi T, Ushio Y (2003) Successful treatment of intracranial nongerminomatous malignant germ cell tumors by administering neoadjuvant chemotherapy and radiotherapy before excision of residual tumors. J Neurosurg 99:106–114CrossRefPubMedGoogle Scholar
  40. 40.
    Sawamura Y, Ikeda J, Shirato H, Tada M, Abe H (1998) Germ cell tumours of the central nervous system: treatment consideration based on 111 cases and their long-term clinical outcomes. Eur J Cancer 34:104–110CrossRefPubMedGoogle Scholar
  41. 41.
    Sano K, Matsutani M, Seto T (1989) So-called intracranial germ cell tumours: personal experiences and a theory of their pathogenesis. Neurol Res 11:118–126PubMedGoogle Scholar
  42. 42.
    Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N, Seto T (1997) Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 86:446–455CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Ioannina School of MedicineIoanninaGreece
  2. 2.Neurosurgical Research InstituteUniversity of IoanninaIoanninaGreece

Personalised recommendations