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Intracranial Germ Cell Tumors

  • Seung-Ki KimEmail author
  • Ji Hoon Phi
  • Sung-Hye Park
  • Kyu-Chang Wang
Chapter

Abstract

Intracranial germ cell tumors (IGCTs) are a very peculiar group of neoplasms arising in the brain. Several characteristics distinguish them from other brain tumors of neuroepithelial origin. First, IGCTs consist of closely related but extremely heterogeneous tumors with a distinct histology and biology, and these tumors can be considered as separate entities on several specific features. Second, IGCTs exhibit strong predilections for onset age, sex, brain location, and worldwide geographical distribution. Although other brain tumors share these epidemiological characteristics, the general properties of IGCTs are incomparable to those of the other tumors. Third, IGCT is considered to be a germ cell tumor (GCT) that arises from various locations in the body including the gonads and extragonadal sites. Because IGCTs and GCTs share similar biological and clinical features, much of our knowledge on the pathogenesis, diagnosis, and treatment of IGCT comes from experience with other GCTs. Fourth, as with other GCTs, many IGCTs are accompanied by elevated levels of tumor markers in the serum and cerebrospinal fluids (CSF). This provides us with an unparalleled opportunity for diagnosis and follow-up, but the uncertainties regarding IGCTs continue to offer challenges. Finally, with some exceptions, IGCTs have relatively good prognoses even though the majority of the diseases are malignant in nature. Furthermore, the necessity of surgery can be negated in some patients because IGCTs respond well to radiation therapy (RT) and chemotherapy. Consequently, therapeutic protocols for IGCT differ considerably, especially when combined with the heterogeneity of IGCTs. Thus, collaborative research for clinical standards is urgently needed.

Keywords

Germ cell tumor Germinoma Intracranial Diagnosis Treatment 

References

  1. 1.
    Dho YS, Jung KW, Ha J, Seo Y, Park CK, Won YJ et al (2017) An updated nationwide epidemiology of primary brain tumors in Republic of Korea, 2013. Brain Tumor Res Treat 5(1):16–23PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Murray MJ, Horan G, Lowis S, Nicholson JC (2013) Highlights from the Third International Central Nervous System Germ Cell Tumour symposium: laying the foundations for future consensus. Ecancermedicalscience 7:333PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Poynter JN, Fonstad R, Tolar J, Spector LG, Ross JA (2014) Incidence of intracranial germ cell tumors by race in the United States, 1992-2010. J Neuro-Oncol 120(2):381–388CrossRefGoogle Scholar
  4. 4.
    Makino K, Nakamura H, Yano S, Kuratsu J (2010) Population-based epidemiological study of primary intracranial tumors in childhood. Childs Nerv Syst 26(8):1029–1034PubMedCrossRefGoogle Scholar
  5. 5.
    McCarthy BJ, Shibui S, Kayama T, Miyaoka E, Narita Y, Murakami M et al (2012) Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries. Neuro-Oncology 14(9):1194–1200PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Sonoda Y, Kumabe T, Sugiyama S, Kanamori M, Yamashita Y, Saito R et al (2008) Germ cell tumors in the basal ganglia: problems of early diagnosis and treatment. J Neurosurg Pediatr 2(2):118–124PubMedCrossRefGoogle Scholar
  7. 7.
    Phi JH, Cho BK, Kim SK, Paeng JC, Kim IO, Kim IH et al (2010) Germinomas in the basal ganglia: magnetic resonance imaging classification and the prognosis. J Neuro-Oncol 99(2):227–236CrossRefGoogle Scholar
  8. 8.
    Koh EJ, Phi JH, Park SH, Kim IO, Cheon JE, Wang KC et al (2009) Mixed germ cell tumor of the midbrain. Case report. J Neurosurg Pediatr 4(2):137–142PubMedCrossRefGoogle Scholar
  9. 9.
    Matsumura N, Kurimoto M, Endo S, Fukuda O, Takaku A (1998) Intracranial germinoma associated with Down’s syndrome. Report of 2 cases. Pediatr Neurosurg 29(4):199–202PubMedCrossRefGoogle Scholar
  10. 10.
    Prall JA, McGavran L, Greffe BS, Partington MD (1995) Intracranial malignant germ cell tumor and the Klinefelter syndrome. Case report and review of the literature. Pediatr Neurosurg 23(4):219–224PubMedCrossRefGoogle Scholar
  11. 11.
    Teilum G (1965) Classification of endodermal sinus tumour (mesoblatoma vitellinum) and so-called “embryonal carcinoma” of the ovary. Acta Pathol Microbiol Scand 64(4):407–429PubMedCrossRefGoogle Scholar
  12. 12.
    Oosterhuis JW, Stoop H, Honecker F, Looijenga LH (2007) Why human extragonadal germ cell tumours occur in the midline of the body: old concepts, new perspectives. Int J Androl 30(4):256–263; discussion 63–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Sobis H, Vandeputte M (1976) Yolk sac-derived rat teratomas are not of germ cell origin. Dev Biol 51(2):320–323PubMedCrossRefGoogle Scholar
  14. 14.
    Solter D, Dominis M, Damjanov I (1980) Embryo-derived teratocarcinoma. II. Teratocarcinogenesis depends on the type of embryonic graft. Int J Cancer 25(3):341–343PubMedCrossRefGoogle Scholar
  15. 15.
    Sano K (1999) Pathogenesis of intracranial germ cell tumors reconsidered. J Neurosurg 90(2):258–264PubMedCrossRefGoogle Scholar
  16. 16.
    Fukushima S, Yamashita S, Kobayashi H, Takami H, Fukuoka K, Nakamura T et al (2017) Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathol 133(3):445–462PubMedCrossRefGoogle Scholar
  17. 17.
    Santagata S, Ligon KL, Hornick JL (2007) Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors. Am J Surg Pathol 31(6):836–845PubMedCrossRefGoogle Scholar
  18. 18.
    Sukov WR, Cheville JC, Giannini C, Carlson AW, Shearer BM, Sinnwell JP et al (2010) Isochromosome 12p and polysomy 12 in primary central nervous system germ cell tumors: frequency and association with clinicopathologic features. Hum Pathol 41(2):232–238PubMedCrossRefGoogle Scholar
  19. 19.
    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(6):531–538PubMedCrossRefGoogle Scholar
  20. 20.
    Fukushima S, Otsuka A, Suzuki T, Yanagisawa T, Mishima K, Mukasa A et al (2014) Mutually exclusive mutations of KIT and RAS are associated with KIT mRNA expression and chromosomal instability in primary intracranial pure germinomas. Acta Neuropathol 127(6):911–925PubMedCrossRefGoogle Scholar
  21. 21.
    Wang L, Yamaguchi S, Burstein MD, Terashima K, Chang K, Ng HK et al (2014) Novel somatic and germline mutations in intracranial germ cell tumours. Nature 511(7508):241–245PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    O’Connor DM, Norris HJ (1994) The influence of grade on the outcome of stage I ovarian immature (malignant) teratomas and the reproducibility of grading. Int J Gynecol Pathol 13(4):283–289PubMedCrossRefGoogle Scholar
  23. 23.
    Phi JH, Park SH, Paek SH, Kim SK, Lee YJ, Park CK et al (2007) Expression of Sox2 in mature and immature teratomas of central nervous system. Mod Pathol 20(7):742–748PubMedCrossRefGoogle Scholar
  24. 24.
    Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N et al (1997) Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 86(3):446–455PubMedCrossRefGoogle Scholar
  25. 25.
    Ogino H, Shibamoto Y, Takanaka T, Suzuki K, Ishihara S, Yamada T et al (2005) CNS germinoma with elevated serum human chorionic gonadotropin level: clinical characteristics and treatment outcome. Int J Radiat Oncol Biol Phys 62(3):803–808PubMedCrossRefGoogle Scholar
  26. 26.
    Shibamoto Y, Takahashi M, Sasai K (1997) Prognosis of intracranial germinoma with syncytiotrophoblastic giant cells treated by radiation therapy. Int J Radiat Oncol Biol Phys 37(3):505–510PubMedCrossRefGoogle Scholar
  27. 27.
    Jorsal T, Rorth M (2012) Intracranial germ cell tumours. A review with special reference to endocrine manifestations. Acta Oncol (Stockholm, Sweden) 51(1):3–9CrossRefGoogle Scholar
  28. 28.
    Mootha SL, Barkovich AJ, Grumbach MM, Edwards MS, Gitelman SE, Kaplan SL et al (1997) Idiopathic hypothalamic diabetes insipidus, pituitary stalk thickening, and the occult intracranial germinoma in children and adolescents. J Clin Endocrinol Metab 82(5):1362–1367PubMedGoogle Scholar
  29. 29.
    Phi JH, Kim SK, Park SH, Hong SH, Wang KC, Cho BK (2005) Immature teratomas of the central nervous system: is adjuvant therapy mandatory? J Neurosurg 103(6 Suppl):524–530PubMedGoogle Scholar
  30. 30.
    Murray MJ, Bartels U, Nishikawa R, Fangusaro J, Matsutani M, Nicholson JC (2015) Consensus on the management of intracranial germ-cell tumours. Lancet Oncol 16(9):e470–e477PubMedCrossRefGoogle Scholar
  31. 31.
    Legault G, Allen JC (2013) Potential role of ventricular tumor markers in CNS germ cell tumors. Pediatr Blood Cancer 60(10):1647–1650PubMedCrossRefGoogle Scholar
  32. 32.
    Kato T, Sawamura Y, Tada M, Murata J, Abe H, Shirato H et al (1998) Occult neurohypophyseal germinomas in patients presenting with central diabetes insipidus. Neurosurg Focus 5(1):e6PubMedCrossRefGoogle Scholar
  33. 33.
    Phi JH, Kim SK, Lee J, Park CK, Kim IH, Ahn HS et al (2013) The enigma of bifocal germ cell tumors in the suprasellar and pineal regions: synchronous lesions or metastasis? J Neurosurg Pediatr 11(2):107–114PubMedCrossRefGoogle Scholar
  34. 34.
    Lafay-Cousin L, Millar BA, Mabbott D, Spiegler B, Drake J, Bartels U et al (2006) Limited-field radiation for bifocal germinoma. Int J Radiat Oncol Biol Phys 65(2):486–492PubMedCrossRefGoogle Scholar
  35. 35.
    Reddy AT, Wellons JC 3rd, Allen JC, Fiveash JB, Abdullatif H, Braune KW et al (2004) Refining the staging evaluation of pineal region germinoma using neuroendoscopy and the presence of preoperative diabetes insipidus. Neuro-Oncology 6(2):127–133PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Takeda N, Fujita K, Katayama S, Uchihashi Y, Okamura Y, Nigami H et al (2004) Germinoma of the basal ganglia. An 8-year asymptomatic history after detection of abnormality on CT. Pediatr Neurosurg 40(6):306–311PubMedCrossRefGoogle Scholar
  37. 37.
    Sudo A, Shiga T, Okajima M, Takano K, Terae S, Sawamura Y et al (2003) High uptake on 11C-methionine positron emission tomographic scan of basal ganglia germinoma with cerebral hemiatrophy. AJNR Am J Neuroradiol 24(9):1909–1911PubMedGoogle Scholar
  38. 38.
    Phuakpet K, Larouche V, Hawkins C, Huang A, Tabori U, Bartels UK et al (2016) Rare presentation of supratentorial primitive neuroectodermal tumors mimicking bifocal germ cell tumors: 2 case reports. J Pediatr Hematol Oncol 38(2):e67–e70PubMedCrossRefGoogle Scholar
  39. 39.
    Kim CY, Choi JW, Lee JY, Kim SK, Wang KC, Park SH et al (2011) Intracranial growing teratoma syndrome: clinical characteristics and treatment strategy. J Neuro-Oncol 101(1):109–115CrossRefGoogle Scholar
  40. 40.
    Rogers SJ, Mosleh-Shirazi MA, Saran FH (2005) Radiotherapy of localised intracranial germinoma: time to sever historical ties? Lancet Oncol 6(7):509–519PubMedCrossRefGoogle Scholar
  41. 41.
    Odagiri K, Omura M, Hata M, Aida N, Niwa T, Ogino I et al (2012) Treatment outcomes, growth height, and neuroendocrine functions in patients with intracranial germ cell tumors treated with chemoradiation therapy. Int J Radiat Oncol Biol Phys 84(3):632–638PubMedCrossRefGoogle Scholar
  42. 42.
    Cheng S, Kilday JP, Laperriere N, Janzen L, Drake J, Bouffet E et al (2016) Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation. J Neuro-Oncol 127(1):173–180CrossRefGoogle Scholar
  43. 43.
    Cho J, Choi JU, Kim DS, Suh CO (2009) Low-dose craniospinal irradiation as a definitive treatment for intracranial germinoma. Radiother Oncol 91(1):75–79PubMedCrossRefGoogle Scholar
  44. 44.
    Calaminus G, Kortmann R, Worch J, Nicholson JC, Alapetite C, Garre ML et al (2013) 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-Oncology 15(6):788–796PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    da Silva NS, Cappellano AM, Diez B, Cavalheiro S, Gardner S, Wisoff J et al (2010) Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study. Pediatr Blood Cancer 54(3):377–383PubMedCrossRefGoogle Scholar
  46. 46.
    Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L et al (2004) Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach. Pediatr Blood Cancer 43(2):126–133PubMedCrossRefGoogle Scholar
  47. 47.
    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 (Oxford, England: 1990) 34(1):104–110CrossRefGoogle Scholar
  48. 48.
    Kim JW, Kim WC, Cho JH, Kim DS, Shim KW, Lyu CJ et al (2012) A multimodal approach including craniospinal irradiation improves the treatment outcome of high-risk intracranial nongerminomatous germ cell tumors. Int J Radiat Oncol Biol Phys 84(3):625–631PubMedCrossRefGoogle Scholar
  49. 49.
    Lai IC, Wong TT, Shiau CY, Hu YW, Ho DM, Chang KP et al (2015) Treatment results and prognostic factors for intracranial nongerminomatous germ cell tumors: single institute experience. Childs Nerv Syst 31(5):683–691PubMedCrossRefGoogle Scholar
  50. 50.
    Calaminus G, Bamberg M, Jurgens H, Kortmann RD, Sorensen N, Wiestler OD et al (2004) Impact of surgery, chemotherapy and irradiation on long term outcome of intracranial malignant non-germinomatous germ cell tumors: results of the German Cooperative Trial MAKEI 89. Klin Padiatr 216(3):141–149PubMedCrossRefGoogle Scholar
  51. 51.
    Goldman S, Bouffet E, Fisher PG, Allen JC, Robertson PL, Chuba PJ et al (2015) 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 33(22):2464–2471PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Weiner HL, Lichtenbaum RA, Wisoff JH, Snow RB, Souweidane MM, Bruce JN et al (2002) Delayed surgical resection of central nervous system germ cell tumors. Neurosurgery 50(4):727–733; discussion 33–4.PubMedCrossRefGoogle Scholar
  53. 53.
    Ogiwara H, Kiyotani C, Terashima K, Morota N (2015) Second-look surgery for intracranial germ cell tumors. Neurosurgery 76(6):658–661; discussion 61–2.PubMedCrossRefGoogle Scholar
  54. 54.
    Souweidane MM, Krieger MD, Weiner HL, Finlay JL (2010) 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 6(2):125–130PubMedCrossRefGoogle Scholar
  55. 55.
    Hanakita S, Takenobu A, Kambe A, Watanabe T, Shin M, Teraoka A (2012) Intramedullary recurrence of germinoma in the spinal cord 15 years after complete remission of a pineal lesion. J Neurosurg Spine 16(5):513–515PubMedCrossRefGoogle Scholar
  56. 56.
    Ohno M, Narita Y, Miyakita Y, Shibui S (2016) The necessity of long-term follow-up including spinal examination after successful initial treatment of intracranial germinoma: case reports. Childs Nerv Syst 32(3):547–551PubMedCrossRefGoogle Scholar
  57. 57.
    Sivasubramaniam V, Zebian B, Thakur B, Saran F, Chandler C (2016) Germinoma recurrence in the conus medullaris 12 years after remission of primary intracranial lesion in the pituitary. J Clin Neurosci 25:150–152PubMedCrossRefGoogle Scholar
  58. 58.
    Mabbott DJ, Monsalves E, Spiegler BJ, Bartels U, Janzen L, Guger S et al (2011) Longitudinal evaluation of neurocognitive function after treatment for central nervous system germ cell tumors in childhood. Cancer 117(23):5402–5411PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Seung-Ki Kim
    • 1
    • 2
    Email author
  • Ji Hoon Phi
    • 1
  • Sung-Hye Park
    • 3
  • Kyu-Chang Wang
    • 1
  1. 1.Division of Pediatric NeurosurgerySeoul National University Children’s HospitalSeoulRepublic of Korea
  2. 2.Department of NeurosurgerySeoul National University College of MedicineSeoulRepublic of Korea
  3. 3.Department of PathologySeoul National University HospitalSeoulRepublic of Korea

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