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Intracranial germ cell tumors

Jack M Su, MD, MS
Section Editors
Jay S Loeffler, MD
Patrick Y Wen, MD
Amar Gajjar, MD
Deputy Editor
April F Eichler, MD, MPH


Germ cell tumors (GCTs) are classified as extragonadal if there is no evidence of a primary tumor in either the testes or the ovaries. Extragonadal GCTs typically arise in midline locations, and specific sites vary with age. In adults, the most common sites are the anterior mediastinum, retroperitoneum, and the pineal and suprasellar regions. In infants and young children, intracranial GCTs and sacrococcygeal teratomas are more common than other locations.

Intracranial GCTs are discussed here. Throughout the text we generally do not distinguish between children and adults. It is important to note, however, that the literature on intracranial GCTs is largely based on children under the age of 15 years, and historical data and outcomes are being extrapolated to young adults based on a small proportion of these patients in most series.

Sacrococcygeal teratomas and extragonadal GCTs arising in the mediastinum and retroperitoneum are discussed elsewhere. (See "Sacrococcygeal germ cell tumors" and "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum".)


In North America and Europe, intracranial GCTs represent 0.5 to 3 percent of pediatric central nervous system (CNS) tumors [1]. In contrast, these tumors are substantially more frequent in Japan and other Asian countries, with a reported incidence of up to 11 percent of pediatric CNS tumors [1]. Even in the United States, individuals with Asian/Pacific Islander ancestry have a two- to threefold higher risk of intracranial GCT compared with whites, suggesting that genetic factors may be more important than environmental factors in the etiology of GCT [2].

The peak incidence of intracranial GCT is during the second decade of life, with a median age at diagnosis of 10 to 12 years. There is a male preponderance of between 2:1 to 3:1, especially with tumors in the pineal region [3,4].

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Literature review current through: Nov 2017. | This topic last updated: May 24, 2017.
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  1. Echevarría ME, Fangusaro J, Goldman S. Pediatric central nervous system germ cell tumors: a review. Oncologist 2008; 13:690.
  2. Poynter JN, Fonstad R, Tolar J, et al. Incidence of intracranial germ cell tumors by race in the United States, 1992-2010. J Neurooncol 2014; 120:381.
  3. Jennings MT, Gelman R, Hochberg F. Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg 1985; 63:155.
  4. Hoffman HJ, Otsubo H, Hendrick EB, et al. Intracranial germ-cell tumors in children. J Neurosurg 1991; 74:545.
  5. Palmer RD, Foster NA, Vowler SL, et al. Malignant germ cell tumours of childhood: new associations of genomic imbalance. Br J Cancer 2007; 96:667.
  6. Schneider DT, Zahn S, Sievers S, et al. Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. Mod Pathol 2006; 19:864.
  7. Rickert CH, Simon R, Bergmann M, et al. Comparative genomic hybridization in pineal germ cell tumors. J Neuropathol Exp Neurol 2000; 59:815.
  8. Terashima K, Yu A, Chow WY, et al. Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. Pediatr Blood Cancer 2014; 61:593.
  9. Okada Y, Nishikawa R, Matsutani M, Louis DN. Hypomethylated X chromosome gain and rare isochromosome 12p in diverse intracranial germ cell tumors. J Neuropathol Exp Neurol 2002; 61:531.
  10. Kamakura Y, Hasegawa M, Minamoto T, et al. C-kit gene mutation: common and widely distributed in intracranial germinomas. J Neurosurg 2006; 104:173.
  11. Sakuma Y, Sakurai S, Oguni S, et al. c-kit gene mutations in intracranial germinomas. Cancer Sci 2004; 95:716.
  12. Wang L, Yamaguchi S, Burstein MD, et al. Novel somatic and germline mutations in intracranial germ cell tumours. Nature 2014; 511:241.
  13. Fukushima S, Otsuka A, Suzuki T, et al. Mutually exclusive mutations of KIT and RAS are associated with KIT mRNA expression and chromosomal instability in primary intracranial pure germinomas. Acta Neuropathol 2014; 127:911.
  14. Ichimura K, Fukushima S, Totoki Y, et al. Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy. Acta Neuropathol 2016; 131:889.
  15. Rosenblum MK, Nakazato Y, Matsutani M. CNS germ cell tumors. In: WHO Classification of Tumours of the Central Nervous System, 3rd, Louis D, Ohgaki H, Wiestler O, Cavenee WK (Eds), WHO Publication Center, Albany, NY 2007. p.197.
  16. Ogino H, Shibamoto Y, Takanaka T, et al. CNS germinoma with elevated serum human chorionic gonadotropin level: clinical characteristics and treatment outcome. Int J Radiat Oncol Biol Phys 2005; 62:803.
  17. Shibamoto Y, Takahashi M, Sasai K. Prognosis of intracranial germinoma with syncytiotrophoblastic giant cells treated by radiation therapy. Int J Radiat Oncol Biol Phys 1997; 37:505.
  18. Matsutani M, Sano K, Takakura K, et al. Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 1997; 86:446.
  19. Matsutani M, Japanese Pediatric Brain Tumor Study Group. Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience. J Neurooncol 2001; 54:311.
  20. Kim DI, Yoon PH, Ryu YH, et al. MRI of germinomas arising from the basal ganglia and thalamus. Neuroradiology 1998; 40:507.
  21. Tamaki N, Lin T, Shirataki K, et al. Germ cell tumors of the thalamus and the basal ganglia. Childs Nerv Syst 1990; 6:3.
  22. Sethi RV, Marino R, Niemierko A, et al. Delayed diagnosis in children with intracranial germ cell tumors. J Pediatr 2013; 163:1448.
  23. Packer RJ, Cohen BH, Cooney K. Intracranial germ cell tumors. Oncologist 2000; 5:312.
  24. Liang L, Korogi Y, Sugahara T, et al. MRI of intracranial germ-cell tumours. Neuroradiology 2002; 44:382.
  25. Douglas-Akinwande AC, Ying J, Momin Z, et al. Diffusion-weighted imaging characteristics of primary central nervous system germinoma with histopathologic correlation: a retrospective study. Acad Radiol 2009; 16:1356.
  26. Ogiwara H, Tsutsumi Y, Matsuoka K, et al. Apparent diffusion coefficient of intracranial germ cell tumors. J Neurooncol 2015; 121:565.
  27. Matsutani M. Treatment of intracranial germ cell tumors: the second phase II study of Japanese GCT Study Group. J Neurooncol 2008; 10:420.
  28. Calaminus G, Frappaz D, Kortmann R, et al. Localized and metastatic nongerminoma treated according to the SIOP CNS GCT 96 protocol: update on risk profiles and outcome. J Neurooncol 2008; 10:418.
  29. Sawamura Y, de Tribolet N, Ishii N, Abe H. Management of primary intracranial germinomas: diagnostic surgery or radical resection? J Neurosurg 1997; 87:262.
  30. Souweidane MM, Krieger MD, Weiner HL, Finlay JL. Surgical management of primary central nervous system germ cell tumors: proceedings from the Second International Symposium on Central Nervous System Germ Cell Tumors. J Neurosurg Pediatr 2010; 6:125.
  31. Bamberg M, Kortmann RD, Calaminus G, et al. Radiation therapy for intracranial germinoma: results of the German cooperative prospective trials MAKEI 83/86/89. J Clin Oncol 1999; 17:2585.
  32. Borg M. Germ cell tumours of the central nervous system in children-controversies in radiotherapy. Med Pediatr Oncol 2003; 40:367.
  33. Haddock MG, Schild SE, Scheithauer BW, Schomberg PJ. Radiation therapy for histologically confirmed primary central nervous system germinoma. Int J Radiat Oncol Biol Phys 1997; 38:915.
  34. Hardenbergh PH, Golden J, Billet A, et al. Intracranial germinoma: the case for lower dose radiation therapy. Int J Radiat Oncol Biol Phys 1997; 39:419.
  35. Wolden SL, Wara WM, Larson DA, et al. Radiation therapy for primary intracranial germ-cell tumors. Int J Radiat Oncol Biol Phys 1995; 32:943.
  36. Sawamura Y, Ikeda J, Shirato H, et al. Germ cell tumours of the central nervous system: treatment consideration based on 111 cases and their long-term clinical outcomes. Eur J Cancer 1998; 34:104.
  37. Jensen AW, Laack NN, Buckner JC, et al. Long-term follow-up of dose-adapted and reduced-field radiotherapy with or without chemotherapy for central nervous system germinoma. Int J Radiat Oncol Biol Phys 2010; 77:1449.
  38. Dattoli MJ, Newall J. Radiation therapy for intracranial germinoma: the case for limited volume treatment. Int J Radiat Oncol Biol Phys 1990; 19:429.
  39. Aoyama H, Shirato H, Kakuto Y, et al. Pathologically-proven intracranial germinoma treated with radiation therapy. Radiother Oncol 1998; 47:201.
  40. Linstadt D, Wara WM, Edwards MS, et al. Radiotherapy of primary intracranial germinomas: the case against routine craniospinal irradiation. Int J Radiat Oncol Biol Phys 1988; 15:291.
  41. Sugiyama K, Uozumi T, Arita K, et al. Clinical evaluation of 33 patients with histologically verified germinoma. Surg Neurol 1994; 42:200.
  42. Haas-Kogan DA, Missett BT, Wara WM, et al. Radiation therapy for intracranial germ cell tumors. Int J Radiat Oncol Biol Phys 2003; 56:511.
  43. Rogers SJ, Mosleh-Shirazi MA, Saran FH. Radiotherapy of localised intracranial germinoma: time to sever historical ties? Lancet Oncol 2005; 6:509.
  44. Shikama N, Ogawa K, Tanaka S, et al. Lack of benefit of spinal irradiation in the primary treatment of intracranial germinoma: a multiinstitutional, retrospective review of 180 patients. Cancer 2005; 104:126.
  45. Allen JC, DaRosso RC, Donahue B, Nirenberg A. A phase II trial of preirradiation carboplatin in newly diagnosed germinoma of the central nervous system. Cancer 1994; 74:940.
  46. Allen JC, Kim JH, Packer RJ. Neoadjuvant chemotherapy for newly diagnosed germ-cell tumors of the central nervous system. J Neurosurg 1987; 67:65.
  47. Buckner JC, Peethambaram PP, Smithson WA, et al. Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors. J Clin Oncol 1999; 17:933.
  48. Fouladi M, Grant R, Baruchel S, et al. Comparison of survival outcomes in patients with intracranial germinomas treated with radiation alone versus reduced-dose radiation and chemotherapy. Childs Nerv Syst 1998; 14:596.
  49. Douglas JG, Rockhill JK, Olson JM, et al. Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas. J Pediatr Hematol Oncol 2006; 28:36.
  50. Kretschmar C, Kleinberg L, Greenberg M, et al. Pre-radiation chemotherapy with response-based radiation therapy in children with central nervous system germ cell tumors: a report from the Children's Oncology Group. Pediatr Blood Cancer 2007; 48:285.
  51. Khatua S, Dhall G, O'Neil S, et al. Treatment of primary CNS germinomatous germ cell tumors with chemotherapy prior to reduced dose whole ventricular and local boost irradiation. Pediatr Blood Cancer 2010; 55:42.
  52. Cheng S, Kilday JP, Laperriere N, et al. Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation. J Neurooncol 2016; 127:173.
  53. Calaminus G, Alapetite C, Frappaz D, et al. Outcome of localized and metastatic germinoma treated according to SIOP CNS GCT 96. J Neurooncol 2008; 10:420.
  54. Alapetite C, Patte C, Frappaz D, et al. Long-term follow-up of intracranial germinoma treated with primary chemotherapy followed by focal radiation treatment: The SFOP-90 experience. Neurooncol 2005; 7:517.
  55. Aoyama H, Shirato H, Ikeda J, et al. Induction chemotherapy followed by low-dose involved-field radiotherapy for intracranial germ cell tumors. J Clin Oncol 2002; 20:857.
  56. Alapetite C, Brisse H, Patte C, et al. Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience. Neuro Oncol 2010; 12:1318.
  57. Calaminus G, Kortmann R, Worch J, et al. SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease. Neuro Oncol 2013; 15:788.
  58. Kellie SJ, Boyce H, Dunkel IJ, et al. Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach. Pediatr Blood Cancer 2004; 43:126.
  59. Balmaceda C, Heller G, Rosenblum M, et al. Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study. J Clin Oncol 1996; 14:2908.
  60. da Silva NS, Cappellano AM, Diez B, et al. Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study. Pediatr Blood Cancer 2010; 54:377.
  61. Shirato H, Aoyama H, Ikeda J, et al. Impact of margin for target volume in low-dose involved field radiotherapy after induction chemotherapy for intracranial germinoma. Int J Radiat Oncol Biol Phys 2004; 60:214.
  62. Matsutani M. Treatment for intracranial germinoma: Final results of the Japanese Study Group. Neurooncology 2005; 7:519.
  63. Mahoney DH Jr, Strother D, Camitta B, et al. High-dose melphalan and cyclophosphamide with autologous bone marrow rescue for recurrent/progressive malignant brain tumors in children: a pilot pediatric oncology group study. J Clin Oncol 1996; 14:382.
  64. Baranzelli M, Pichon F, Patte C, et al. High-dose etoposide and thio-TEPA for recurrent intracranial malignant germ cell tumours. Experiences of SFOP (the French Society of Pediatric Oncology). Childs Nerv Syst 1999; 14:520.
  65. Modak S, Gardner S, Dunkel IJ, et al. Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. J Clin Oncol 2004; 22:1934.
  66. Bouffet E. The role of myeloablative chemotherapy with autologous hematopoietic cell rescue in central nervous system germ cell tumors. Pediatr Blood Cancer 2010; 54:644.
  67. Baek HJ, Park HJ, Sung KW, et al. Myeloablative chemotherapy and autologous stem cell transplantation in patients with relapsed or progressed central nervous system germ cell tumors: results of Korean Society of Pediatric Neuro-Oncology (KSPNO) S-053 study. J Neurooncol 2013; 114:329.
  68. Fuller BG, Kapp DS, Cox R. Radiation therapy of pineal region tumors: 25 new cases and a review of 208 previously reported cases. Int J Radiat Oncol Biol Phys 1994; 28:229.
  69. Robertson PL, Jakacki R, Hukin J, et al. Multimodality therapy for CNS mixed malignant germ cell tumors (MMGCT): results of a phase II multi-institutional study. J Neurooncol 2014; 118:93.
  70. Robertson PL, DaRosso RC, Allen JC. Improved prognosis of intracranial non-germinoma germ cell tumors with multimodality therapy. J Neurooncol 1997; 32:71.
  71. Calaminus G, Bamberg M, Harms D, et al. AFP/beta-HCG secreting CNS germ cell tumors: long-term outcome with respect to initial symptoms and primary tumor resection. Results of the cooperative trial MAKEI 89. Neuropediatrics 2005; 36:71.
  72. Ogawa K, Toita T, Nakamura K, et al. Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients. Cancer 2003; 98:369.
  73. Goldman S, Bouffet E, Fisher PG, et al. Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study. J Clin Oncol 2015; 33:2464.
  74. Calaminus G, Bamberg M, Baranzelli MC, et al. Intracranial germ cell tumors: a comprehensive update of the European data. Neuropediatrics 1994; 25:26.
  75. Kellie SJ, Boyce H, Dunkel IJ, et al. Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. J Clin Oncol 2004; 22:846.
  76. Ushio Y, Kochi M, Kuratsu J, et al. Preliminary observations for a new treatment in children with primary intracranial yolk sac tumor or embryonal carcinoma. Report of five cases. J Neurosurg 1999; 90:133.
  77. Friedman JA, Lynch JJ, Buckner JC, et al. Management of malignant pineal germ cell tumors with residual mature teratoma. Neurosurgery 2001; 48:518.
  78. Weiner HL, Lichtenbaum RA, Wisoff JH, et al. Delayed surgical resection of central nervous system germ cell tumors. Neurosurgery 2002; 50:727.
  79. Kochi M, Itoyama Y, Shiraishi S, et al. Successful treatment of intracranial nongerminomatous malignant germ cell tumors by administering neoadjuvant chemotherapy and radiotherapy before excision of residual tumors. J Neurosurg 2003; 99:106.
  80. Logothetis CJ, Samuels ML, Trindade A, Johnson DE. The growing teratoma syndrome. Cancer 1982; 50:1629.
  81. Finlay J, Kriegger M, Nasta A, et al. Treatment of primary CNS germinomatous germ cell tumors (GCT) with chemotherapy prior to reduced-dose ventricular field irradiation: The Children's Hospital Los Angeles Experience 2003-2007. J Neurooncol 2008; 10:421.
  82. Rustin GJ, Newlands ES, Bagshawe KD, et al. Successful management of metastatic and primary germ cell tumors in the brain. Cancer 1986; 57:2108.
  83. Lee AC, Chan GC, Fung CF, et al. Paradoxical response of a pineal immature teratoma to combination chemotherapy. Med Pediatr Oncol 1995; 24:53.
  84. O'Callaghan AM, Katapodis O, Ellison DW, et al. The growing teratoma syndrome in a nongerminomatous germ cell tumor of the pineal gland: a case report and review. Cancer 1997; 80:942.
  85. Hanna A, Edan C, Heresbach N, et al. [Expanding mature pineal teratoma syndrome. Case report]. Neurochirurgie 2000; 46:568.
  86. Yagi K, Kageji T, Nagahiro S, Horiguchi H. Growing teratoma syndrome in a patient with a non-germinomatous germ cell tumor in the neurohypophysis--case report. Neurol Med Chir (Tokyo) 2004; 44:33.
  87. Kong DS, Nam DH, Lee JI, et al. Intracranial growing teratoma syndrome mimicking tumor relapse: a diagnostic dilemma. J Neurosurg Pediatr 2009; 3:392.
  88. Kim CY, Choi JW, Lee JY, et al. Intracranial growing teratoma syndrome: clinical characteristics and treatment strategy. J Neurooncol 2011; 101:109.