Abstract
The central nervous system is one of the most frequent sites of involvement by extragonadal germ cell tumors. Most of these occur in midline structures, particularly in the sellar region and pineal gland, as well as other sites to a lesser extent (e.g., basal ganglia). The predominant histologic type is germinoma, the intracranial counterpart to the seminoma in the testis and dysgerminoma in the ovary. As in these other sites, germinoma has an exquisite sensitivity to current treatment and an improved prognosis compared to other germ cell tumor components, all of which may occur in the nervous system. Clinical evaluation of these patients involves neuroimaging and analysis of markers in serum and cerebrospinal fluid for diagnosis and to monitor relapse. Recent sequencing efforts have expanded our knowledge of the biology of these tumors and uncovered a high frequency of somatic mutations in members of the KIT/RAS pathways and mTOR/AKT to a lesser extent, in intracranial germ cell tumors, particularly germinoma. In this review we summarize our current knowledge about the clinicopathologic, phenotypic, and molecular characteristics of intracranial germ cell tumors, highlighting specific properties to intracranial sites.
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References
Fujimaki T. Central nervous system germ cell tumors: classification, clinical features, and treatment with a historical overview. J Child Neurol. 2009;24(11):1439–45. doi:10.1177/0883073809342127.
Murray MJ, Horan G, Lowis S, Nicholson JC. Highlights from the Third International Central Nervous System Germ Cell Tumour symposium: laying the foundations for future consensus. Ecancermedicalscience. 2013;7:333. doi:10.3332/ecancer.2013.333.
Terashima K, Yu A, Chow WY, Hsu WC, Chen P, Wong S, Hung YS, Suzuki T, Nishikawa R, Matsutani M, Nakamura H, Ng HK, Allen JC, Aldape KD, Su JM, Adesina AM, Leung HC, Man TK, Lau CC. Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. Pediatr Blood Cancer. 2014;61(4):593–600. doi:10.1002/pbc.24833.
McCarthy BJ, Shibui S, Kayama T, Miyaoka E, Narita Y, Murakami M, Matsuda A, Matsuda T, Sobue T, Palis BE, Dolecek TA, Kruchko C, Engelhard HH, Villano JL. Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries. Neuro-Oncology. 2012;14(9):1194–200. doi:10.1093/neuonc/nos155.
Thakkar JP, Chew L, Villano JL. Primary CNS germ cell tumors: current epidemiology and update on treatment. Med Oncol. 2013;30(2):496. doi:10.1007/s12032-013-0496-9.
Hoffman HJ, Otsubo H, Hendrick EB, Humphreys RP, Drake JM, Becker LE, Greenberg M, Jenkin D. Intracranial germ-cell tumors in children. J Neurosurg. 1991;74(4):545–51. doi:10.3171/jns.1991.74.4.0545.
Central brain tumor registry of the United States statistical report supplement. Neuro-Oncology. 2014;16.
Goodwin TL, Sainani K, Fisher PG. Incidence patterns of central nervous system germ cell tumors: a SEER Study. J Pediatr Hematol Oncol. 2009;31(8):541–4. doi:10.1097/MPH.0b013e3181983af5.
Jennings MT, Gelman R, Hochberg F. Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg. 1985;63(2):155–67. doi:10.3171/jns.1985.63.2.0155.
Packer RJ, Cohen BH, Cooney K. Intracranial germ cell tumors. Oncologist. 2000;5(4):312–20.
Arens R, Marcus D, Engelberg S, Findler G, Goodman RM, Passwell JH. Cerebral germinomas and Klinefelter syndrome. A review. Cancer. 1988;61(6):1228–31.
Maeda Y, Yoshikawa K, Kajiwara K, Ideguchi M, Amano T, Saka M, Nomura S, Fujii M, Suzuki M. Intracranial yolk sac tumor in a patient with Down syndrome. J Neurosurg Pediatr. 2011;7(6):604–8. doi:10.3171/2011.3.PEDS10500.
Sugimoto K, Ideguchi M, Sadahiro H, Yoshikawa K, Goto H, Nomura S, Fujii M, Suzuki M. Yolk sac tumor of the bilateral basal ganglia in a patient with Down syndrome. Brain Tumor Pathol. 2013;30(4):247–52. doi:10.1007/s10014-012-0134-9.
Queipo G, Aguirre D, Nieto K, Pena YR, Palma I, Olvera J, Chavez L, Najera N, Kofman-Alfaro S. Intracranial germ cell tumors: association with Klinefelter syndrome and sex chromosome aneuploidies. Cytogenet Genome Res. 2008;121(3–4):211–4. doi:10.1159/000138887.
Louis D, Ohgaki H, Wiestler OD, Cavenee WK. WHO classification of tumours of the central nervous system. 4th ed. Lyon: IARC Press; 2007.
Fukushima S, Otsuka A, Suzuki T, Yanagisawa T, Mishima K, Mukasa A, Saito N, Kumabe T, Kanamori M, Tominaga T, Narita Y, Shibui S, Kato M, Shibata T, Matsutani M, Nishikawa R, Ichimura K, Intracranial Germ Cell Tumor Genome Analysis Consortium (iGCT Consortium). 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:(6):911–25. doi:10.1007/s00401-014-1247-5.
Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM. Delayed diagnosis in children with intracranial germ cell tumors. J Pediatr. 2013;163(5):1448–53. doi:10.1016/j.jpeds.2013.06.024.
Echevarria ME, Fangusaro J, Goldman S. Pediatric central nervous system germ cell tumors: a review. Oncologist. 2008;13(6):690–9. doi:10.1634/theoncologist.2008-0037.
Lee D, Suh YL. Histologically confirmed intracranial germ cell tumors; an analysis of 62 patients in a single institute. Virchows Archiv Int J Pathol. 2010;457(3):347–57. doi:10.1007/s00428-010-0951-3.
Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N, Seto T. Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg. 1997;86(3):446–55. doi:10.3171/jns.1997.86.3.0446.
Ozelame RV, Shroff M, Wood B, Bouffet E, Bartels U, Drake JM, Hawkins C, Blaser S. Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy. Pediatr Radiol. 2006;36(4):325–30. doi:10.1007/s00247-005-0063-4.
Phi JH, Cho BK, Kim SK, Paeng JC, Kim IO, Kim IH, Kim DG, Jung HW, Kim JE, Wang KC. Germinomas in the basal ganglia: magnetic resonance imaging classification and the prognosis. J Neuro-Oncol. 2010;99(2):227–36. doi:10.1007/s11060-010-0119-7.
Sonoda Y, Kumabe T, Sugiyama S, Kanamori M, Yamashita Y, Saito R, Ariga H, Takai Y, Tominaga T. Germ cell tumors in the basal ganglia: problems of early diagnosis and treatment. J Neurosurg Pediatr. 2008;2(2):118–24. doi:10.3171/PED/2008/2/8/118.
Phi JH, Kim SK, Lee YA, Shin CH, Cheon JE, Kim IO, Yang SW, Wang KC. Latency of intracranial germ cell tumors and diagnosis delay. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg. 2013;29(10):1871–81. doi:10.1007/s00381-013-2164-y.
Weksberg DC, Shibamoto Y, Paulino AC. Bifocal intracranial germinoma: a retrospective analysis of treatment outcomes in 20 patients and review of the literature. Int J Radiat Oncol Biol Phys. 2012;82(4):1341–51. doi:10.1016/j.ijrobp.2011.04.033.
Cuccia V, Alderete D. Suprasellar/pineal bifocal germ cell tumors. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg. 2010;26(8):1043–9. doi:10.1007/s00381-010-1120-3.
Phi JH, Kim SK, Lee J, Park CK, Kim IH, Ahn HS, Shin HY, Kim IO, Jung HW, Kim DG, Paek SH, Wang KC. The enigma of bifocal germ cell tumors in the suprasellar and pineal regions: synchronous lesions or metastasis? J Neurosurg Pediatr. 2013;11(2):107–14. doi:10.3171/2012.10.PEDS11487.
Tsugu H, Oshiro S, Ueno Y, Abe H, Komatsu F, Sakamoto S, Matsumoto S, Nabeshima K, Fukushima T, Inoue T. Primary yolk sac tumor within the lateral ventricle. Neurol Med Chir. 2009;49(11):528–31.
DiLuna ML, Two AM, Levy GH, Patel T, Huttner AJ, Duncan CC, Piepmeier JM. Primary, non-exophytic, optic nerve germ cell tumors. J Neuro-Oncol. 2009;95(3):437–43. doi:10.1007/s11060-009-9941-1.
Legault G, Allen JC. Potential role of ventricular tumor markers in CNS germ cell tumors. Pediatr Blood Cancer. 2013;60(10):1647–50. doi:10.1002/pbc.24620.
Mei K, Liu A, Allan RW, Wang P, Lane Z, Abel TW, Wei L, Cheng H, Guo S, Peng Y, Rakheja D, Wang M, Ma J, Rodriguez MM, Li J, Cao D. Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases. Mod Pathol Off J United States Can Acad Pathol Inc. 2009;22(12):1628–36. doi:10.1038/modpathol.2009.148.
Hattab EM, Tu PH, Wilson JD, Cheng L. OCT4 immunohistochemistry is superior to placental alkaline phosphatase (PLAP) in the diagnosis of central nervous system germinoma. Am J Surg Pathol. 2005;29(3):368–71.
Wanggou S, Jiang X, Li Q, Zhang L, Liu D, Li G, Feng X, Liu W, Zhu B, Huang W, Shi J, Yuan X, Ren C. HESRG: a novel biomarker for intracranial germinoma and embryonal carcinoma. J Neuro-Oncol. 2012;106(2):251–9. doi:10.1007/s11060-011-0673-7.
Villano JL, Virk IY, Ramirez V, Propp JM, Engelhard HH, McCarthy BJ. Descriptive epidemiology of central nervous system germ cell tumors: nonpineal analysis. Neuro-Oncology. 2010;12(3):257–64. doi:10.1093/neuonc/nop029.
Sakuma Y, Sakurai S, Oguni S, Hironaka M, Saito K. Alterations of the c-kit gene in testicular germ cell tumors. Cancer Sci. 2003;94(6):486–91.
Wang L, Yamaguchi S, Burstein MD, Terashima K, Chang K, Ng HK, Nakamura H, He Z, Doddapaneni H, Lewis L, Wang M, Suzuki T, Nishikawa R, Natsume A, Terasaka S, Dauser R, Whitehead W, Adekunle A, Sun J, Qiao Y, Marth G, Muzny DM, Gibbs RA, Leal SM, Wheeler DA, Lau CC. Novel somatic and germline mutations in intracranial germ cell tumours. Nature. 2014;511(7508):241–5. doi:10.1038/nature13296.
Kamakura Y, Hasegawa M, Minamoto T, Yamashita J, Fujisawa H. C-kit gene mutation: common and widely distributed in intracranial germinomas. J Neurosurg. 2006;104(3 Suppl):173–80. doi:10.3171/ped.2006.104.3.173.
Schneider DT, Zahn S, Sievers S, Alemazkour K, Reifenberger G, Wiestler OD, Calaminus G, Gobel U, Perlman EJ. Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. Mod Pathol Off J United States Can Acad Pathol Inc. 2006;19(6):864–73. doi:10.1038/modpathol.3800607.
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(6):531–8.
Lemos JA, Barbieri-Neto J, Casartelli C. Primary intracranial germ cell tumors without an isochromosome 12p. Cancer Genet Cytogenet. 1998;100(2):124–8.
Sukov WR, Cheville JC, Giannini C, Carlson AW, Shearer BM, Sinnwell JP, Ketterling RP. Isochromosome 12p and polysomy 12 in primary central nervous system germ cell tumors: frequency and association with clinicopathologic features. Hum Pathol. 2010;41(2):232–8. doi:10.1016/j.humpath.2009.07.017.
Kim JW, Kim WC, Cho JH, Kim DS, Shim KW, Lyu CJ, Won SC, Suh CO. A multimodal approach including craniospinal irradiation improves the treatment outcome of high-risk intracranial nongerminomatous germ cell tumors. Int J Radiat Oncol Biol Phys. 2012;84(3):625–31. doi:10.1016/j.ijrobp.2011.12.077.
Louis DN, Ohgaki H, Wiestler OD, Caveneee WK, Ellison DW, Figarella-Branger D, Perry A, Reifenberger G, von Deimling A. WHO Classification of Tumours of the Central Nervous System. Revised 4th edition. Lyon, IARC, 2016.
Fujjimaki T. Central nervous system germ cell tumors: classification, clinical features, and treatment with a historical overview. J Child Neurol. 2009;24:1439.
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Vizcaino, M.A., Rodriguez, F.J. (2017). Central Nervous System Germ Cell Tumors. In: Nogales, F., Jimenez, R. (eds) Pathology and Biology of Human Germ Cell Tumors. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-53775-6_9
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