Sections

Sections Central Nervous System Germinoma
Overview
Presentation
DDx
Workup
Treatment
Medication
Media Gallery
Tables
References

Presentation

History

The clinical presentation in central nervous system (CNS) germ cell tumors (GCTs) varies, depending on the age of patient, the site of the tumor, and the duration of the disease.^{[9, 31, 51, 52]}Typical presentations by age are as follows:

Prenatal/neonate – Congenital teratomas produce polyhydramnios and hydrocephalus; ultrasound will show a heterogeneous echogenic mass with cystic and solid components.
Young infants – The teratoma and choriocarcinoma subtypes of nongerminoma GCT are most common in this age group^[53]; these patients may present with irritability, listlessness, failure to thrive, macrocephaly, and bulging fontanelle
Beyond infancy – Presentation depends on tumor location

Pineal region tumors

Parinaud syndrome is one of the most common presentation in CNS GCTs, seen in 34-50% of cases. It is due to compression of the tectum. The syndrome includes the following ophthalmic manifestations:

Paralysis of upward gaze
Loss of light perception and accommodation
Nystagmus
Failure of convergence

Features of increased intracranial pressure may supervene. These include headache, nausea and vomiting, and papilledema. Somnolence, ataxia, seizures, and behavioral abnormalities may develop.

Precocious puberty may develop in a pre-pubertal child.

Diabetes insipidus and anterior hypopituitarism are rare occurrences and may indicate involvement of the floor of the fourth ventricle and suprasellar area.^[16]

Suprasellar region tumors

Patients with suprasellar GCTs usually present with endocrine deficits. These include the following:

Anterior hypopituitarism and Diabetes insipidus (DI)
Thyroid and/or cortisol deficiency
Growth failure from growth hormone deficiency
Delayed puberty from gonadotropin deficiency
Regression of sexual development or sexual dysfunction
Posterior pituitary dysfunction (vasopressin deficiency)
Precocious puberty may develop in a pre-pubertal child (due to tumor-induced hypothalamic injury or secretion of human chorionic gonadotropin by the tumor).

Visual disturbances may include diplopia, blurred vision, and diminished vision. Enuresis and psychiatric abnormalities may develop.^{[9, 30, 54, 10]}In general, patients with symptoms of increased intracranial pressure and visual changes tend to present earlier in the disease course than patients with endocrine dysfunction.

Rare presentations

Rare presentations of CNS GCTs include the following:

Multiple lesions - GCTs in the pineal, sellar region, corpus callosum, and ventricles was reported in an 18-year-old man who presented with psychosis^[55]
Wide skull base extension - This was reported in a 15-year-old girl with radiologic evidence of central skull base and suprasellar tumor extending into the cavernous sinus, intraorbital region, ethmoid sinus, sphenoid sinus, and pituitary fossa^[56]
Optic pathway - Intracranial germ cell tumors may occur primarily in the optic nerve and/or optic chiasma with progressive, painless visual loss^{[57, 58, 59, 60]}; therefore, biopsy for definitive diagnosis may be required in patients with imaging studies suggestive of optic gliomas who have visual loss with hypothalamic-pituitary-adrenal dysfunction^[61]
Midbrain outflow tremor (Holmes tremor) - Holmes tremor is a hyperkinetic movement disorder that presents as mild to severe tremors, dystonia, and cerebellar deficits; it has been reported in patients with germinoma^{[62, 63]}

Physical Examination

The clinical evaluation should include the following:

General physical examination
Check of growth parameters
Careful neurological evaluation, with assessment for neurocutaneous stigmata
Assessment of primary and secondary sexual characteristics
Ophthalmologic exam

Differential Diagnoses

Villano JL, Propp JM, Porter KR, Stewart AK, Valyi-Nagy T, Li X. Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries. Neuro Oncol. 2008 Apr. 10(2):121-30. [Medline]. [Full Text].
Jennings MT, Gelman R, Hochberg F. Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg. 1985 Aug. 63(2):155-67. [Medline].
Keene D, Johnston D, Strother D, Fryer C, Carret AS, Crooks B. Epidemiological survey of central nervous system germ cell tumors in Canadian children. J Neurooncol. 2007 May. 82(3):289-95. [Medline].
McCarthy BJ, Shibui S, Kayama T, Miyaoka E, Narita Y, Murakami M, et al. Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries. Neuro Oncol. 2012 Sep. 14 (9):1194-200. [Medline]. [Full Text].
Bentley AJ, Parkinson MC, Harding BN, Bains RM, Lantos PL. A comparative morphological and immunohistochemical study of testicular seminomas and intracranial germinomas. Histopathology. 1990 Nov. 17(5):443-9. [Medline].
Germ cell tumours. Louis DN, Ohgaki H, Wiestler OD, and Cavenee WK. WHO Classification of Tumours of the Central Nervous System. 4th Edition. Lyon, France: International Agency for Research on Cancer; 2016. Volume 1: 285-291.
Matsutani M,. Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience. J Neurooncol. 2001 Sep. 54(3):311-6. [Medline].
Goodwin TL, Sainani K, Fisher PG. Incidence patterns of central nervous system germ cell tumors: a SEER Study. J Pediatr Hematol Oncol. 2009 Aug. 31(8):541-4. [Medline].
Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, LaFond DA. CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. Neurology. 2007 May 15. 68(20):1668-73. [Medline].
Malbari F, Gershon TR, Garvin JH, Allen JC, Khakoo Y, Levy AS, et al. Psychiatric manifestations as initial presentation for pediatric CNS germ cell tumors, a case series. Childs Nerv Syst. 2016 Aug. 32 (8):1359-62. [Medline]. [Full Text].
Kretschmar C, Kleinberg L, Greenberg M, Burger P, Holmes E, Wharam M. 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 Mar. 48(3):285-91. [Medline].
Finlay J, da Silva NS, Lavey R, Bouffet E, Kellie SJ, Shaw E, et al. The management of patients with primary central nervous system (CNS) germinoma: current controversies requiring resolution. Pediatr Blood Cancer. 2008 Aug. 51(2):313-6. [Medline].
Murray MJ, Bartels U, Nishikawa R, Fangusaro J, Matsutani M, Nicholson JC. Consensus on the management of intracranial germ-cell tumours. Lancet Oncol. 2015 Sep. 16 (9):e470-e477. [Medline].
Aizer AA, Sethi RV, Hedley-Whyte ET, Ebb D, Tarbell NJ, Yock TI, et al. Bifocal intracranial tumors of nongerminomatous germ cell etiology: diagnostic and therapeutic implications. Neuro Oncol. 2013 Jul. 15 (7):955-60. [Medline]. [Full Text].
Fukushima S, Yamashita S, Kobayashi H, et al. Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathol. 2017 Mar. 133 (3):445-462. [Medline].
Packer RJ, Cohen BH, Cooney K. Intracranial germ cell tumors. Oncologist. 2000. 5(4):312-20. [Medline].
Sano K, Matsutani M, Seto T. So-called intracranial germ cell tumours: personal experiences and a theory of their pathogenesis. Neurol Res. 1989 Jun. 11(2):118-26. [Medline].
Rickert CH, Simon R, Bergmann M, Dockhorn-Dworniczak B, Paulus W. Comparative genomic hybridization in pineal germ cell tumors. J Neuropathol Exp Neurol. 2000 Sep. 59(9):815-21. [Medline].
Schneider DT, Zahn S, Sievers S. Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. Mod Pathol. 2006 Jun. 19(6):864-73.
Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP. Malignant germ cell tumours of childhood: new associations of genomic imbalance. Br J Cancer. 2007 Feb 26. 96(4):667-76. [Medline]. [Full Text].
Sato K, Takeuchi H, Kubota T. Pathology of intracranial germ cell tumors. Prog Neurol Surg. 2009. 23:59-75. [Medline].
Kamakura Y, Hasegawa M, Minamoto T, Yamashita J, Fujisawa H. C-kit gene mutation: common and widely distributed in intracranial germinomas. J Neurosurg. 2006 Mar. 104(3 Suppl):173-80. [Medline].
Sakuma Y, Sakurai S, Oguni S, Satoh M, Hironaka M, Saito K. c-kit gene mutations in intracranial germinomas. Cancer Sci. 2004 Sep. 95(9):716-20. [Medline].
Wang HW, Wu YH, Hsieh JY, et al. Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations. BMC Genomics. 2010 Feb 24. 11:132. [Medline]. [Full Text].
Terashima K, Yu A, Chow WY, Hsu WC, Chen P, Wong S, et al. Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. Pediatr Blood Cancer. 2014 Apr. 61(4):593-600. [Medline].
Wang L, Yamaguchi S, Burstein MD, Terashima K, Chang K, Ng HK, et al. Novel somatic and germline mutations in intracranial germ cell tumours. Nature. 2014 Jul 10. 511(7508):241-5. [Medline].
Zapka P, Dörner E, Dreschmann V, Sakamato N, Kristiansen G, Calaminus G, et al. Type, Frequency, and Spatial Distribution of Immune Cell Infiltrates in CNS Germinomas: Evidence for Inflammatory and Immunosuppressive Mechanisms. J Neuropathol Exp Neurol. 2018 Feb 1. 77 (2):119-127. [Medline].
Takami H, et al; Intracranial Germ Cell Tumor Genome Analysis Consortium (the iGCT Consortium). Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance. Neuropathol Appl Neurobiol. 2019 Jun 10. [Medline].
Takami H, Fukuoka K, Fukushima S, et al. Integrated Clinical, Histopathological, and Molecular Data Analysis of 190 Central Nervous System Germ Cell Tumors from the iGCT Consortium. Neuro Oncol. 2019 Aug 16. [Medline].
Echevarría ME, Fangusaro J, Goldman S. Pediatric central nervous system germ cell tumors: a review. Oncologist. 2008 Jun. 13(6):690-9. [Medline].
Jubran RF, Finlay J. Central nervous system germ cell tumors: controversies in diagnosis and treatment. Oncology (Williston Park). 2005 May. 19(6):705-11; discussion 711-2, 715-7, 721. [Medline].
Pereda J, Motta PM. A unique fibrillar coat on the surface of migrating human primordial germ cells. Arch Histol Cytol. 1991 Oct. 54(4):419-25. [Medline].
Godin I, Wylie CC. TGF beta 1 inhibits proliferation and has a chemotropic effect on mouse primordial germ cells in culture. Development. 1991 Dec. 113(4):1451-7. [Medline].
Horowitz MB, Hall WA. Central nervous system germinomas. A review. Arch Neurol. 1991 Jun. 48(6):652-7. [Medline].
Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C, et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro Oncol. 2017 Nov 6. 19 (suppl_5):v1-v88. [Medline]. [Full Text].
Lee SH, Jung KW, Ha J, Oh CM, Kim H, Park HJ, et al. Nationwide Population-Based Incidence and Survival Rates of Malignant Central Nervous System Germ Cell Tumors in Korea, 2005-2012. Cancer Res Treat. 2017 Apr. 49 (2):494-501. [Medline]. [Full Text].
McCarthy BJ, Shibui S, Kayama T, Miyaoka E, Narita Y, Murakami M. Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries. Neuro Oncol. 2012 Sep. 14(9):1194-200. [Medline].
Calaminus G, Frappaz D, Kortmann RD, Krefeld B, Saran F, Pietsch T, et al. Outcome of patients with intracranial non-germinomatous germ cell tumors-lessons from the SIOP-CNS-GCT-96 trial. Neuro Oncol. 2017 Nov 29. 19 (12):1661-1672. [Medline]. [Full Text].
Goldman S, Bouffet E, Fisher PG, Allen JC, Robertson PL, Chuba PJ, 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 Aug 1. 33 (22):2464-71. [Medline]. [Full Text].
Fukuoka K, Yanagisawa T, Suzuki T, Shirahata M, Adachi JI, Mishima K, et al. Human chorionic gonadotropin detection in cerebrospinal fluid of patients with a germinoma and its prognostic significance: assessment by using a highly sensitive enzyme immunoassay. J Neurosurg Pediatr. 2016 Nov. 18 (5):573-577. [Medline].
Ogino H, Shibamoto Y, Takanaka T, Suzuki K, Ishihara S, Yamada T, et al. CNS germinoma with elevated serum human chorionic gonadotropin level: clinical characteristics and treatment outcome. Int J Radiat Oncol Biol Phys. 2005 Jul 1. 62 (3):803-8. [Medline].
Sugiyama K, Yamasaki F, Kurisu K, Kenjo M. Quality of life of extremely long-time germinoma survivors mainly treated with radiotherapy. Prog Neurol Surg. 2009. 23:130-9. [Medline].
Sutton LN, Radcliffe J, Goldwein JW, Phillips P, Janss AJ, Packer RJ, et al. Quality of life of adult survivors of germinomas treated with craniospinal irradiation. Neurosurgery. 1999 Dec. 45(6):1292-7; discussion 1297-8. [Medline].
Yoshida J, Sugita K, Kobayashi T, Takakura K, Shitara N, Matsutani M, et al. Prognosis of intracranial germ cell tumours: effectiveness of chemotherapy with cisplatin and etoposide (CDDP and VP-16). Acta Neurochir (Wien). 1993. 120(3-4):111-7. [Medline].
Liang SY, Yang TF, Chen YW, Liang ML, Chen HH, Chang KP, et al. Neuropsychological functions and quality of life in survived patients with intracranial germ cell tumors after treatment. Neuro Oncol. 2013 Nov. 15(11):1543-51. [Medline]. [Full Text].
Jinguji S, Yoshimura J, Nishiyama K, Aoki H, Nagasaki K, Natsumeda M, et al. Factors affecting functional outcomes in long-term survivors of intracranial germinomas: a 20-year experience in a single institution. J Neurosurg Pediatr. 2013 Apr. 11(4):454-63. [Medline].
Acharya S, DeWees T, Shinohara ET, Perkins SM. Long-term outcomes and late effects for childhood and young adulthood intracranial germinomas. Neuro Oncol. 2015 May. 17(5):741-6. [Medline].
Martens T, Rotermund R, Zu Eulenburg C, Westphal M, Flitsch J. Long-term follow-up and quality of life in patients with intracranial germinoma. Neurosurg Rev. 2014 Jul. 37(3):445-50; discussion 451. [Medline].
Ogawa K, Shikama N, Toita T, Nakamura K, Uno T, Onishi H, et al. Long-term results of radiotherapy for intracranial germinoma: a multi-institutional retrospective review of 126 patients. Int J Radiat Oncol Biol Phys. 2004 Mar 1. 58(3):705-13. [Medline].
Odagiri K, Omura M, Hata M, Aida N, Niwa T, Ogino I, et al. Treatment outcomes, growth height, and neuroendocrine functions in patients with intracranial germ cell tumors treated with chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2012 Nov 1. 84(3):632-8. [Medline].
Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM. Delayed diagnosis in children with intracranial germ cell tumors. J Pediatr. 2013 Nov. 163(5):1448-53. [Medline].
Phi JH, Kim SK, Lee YA, Shin CH, Cheon JE, Kim IO, et al. Latency of intracranial germ cell tumors and diagnosis delay. Childs Nerv Syst. 2013 Oct. 29(10):1871-81. [Medline].
Goodwin TL, Sainani K, Fisher PG. Incidence patterns of central nervous system germ cell tumors: a SEER Study. J Pediatr Hematol Oncol. 2009 Aug. 31(8):541-4. [Medline].
Sonoda Y, Kumabe T, Sugiyama S, Kanamori M, Yamashita Y, Saito R. Germ cell tumors in the basal ganglia: problems of early diagnosis and treatment. J Neurosurg Pediatr. 2008 Aug. 2(2):118-24. [Medline].
Yang P, Li L, Kuang W, Li B, Zhou B, Yang J, et al. Intracranial multiple germ cell tumors: a case report and review of literature. Int J Clin Exp Pathol. 2014. 7(12):9002-7. [Medline]. [Full Text].
Zhou ZH, Zhang HB, Rao J, Bian XW. Clinical diagnostic dilemma of intracranial germinoma manifesting as wide skull base extension. J Craniofac Surg. 2014 Sep. 25(5):e467-70. [Medline].
Nadkarni TD, Fattepurkar SC, Desai KI, Goel A. Intracranial optic nerve germinoma. J Clin Neurosci. 2004 Jun. 11(5):559-61. [Medline].
Rath S, Vemuganti GK, Biswas G, Mod H. Optic nerve and chiasmal germinoma. Ophthal Plast Reconstr Surg. 2009 Mar-Apr. 25(2):161-3. [Medline].
Chen CH, Lin HL, Cho DY. Reversible hypothalamic dysfunction in optic nerve germinoma. J Craniofac Surg. 2013 Mar. 24(2):468-9. [Medline].
Chaudhry NS, Ahmad FU, Whittington E, Schatz N, Morcos JJ. Primary Intrinsic Chiasmal Germinoma. J Neuroophthalmol. 2015 Jan 22. [Medline].
Wilson JT, Wald SL, Aitken PA, Mastromateo J, Vieco PT. Primary diffuse chiasmatic germinomas: differentiation from optic chiasm gliomas. Pediatr Neurosurg. 1995. 23(1):1-5; discussion 6. [Medline].
Strowd RE, Burger P, Holdhoff M, Kleinberg L, Okun MS, Olivi A, et al. Steroid-responsive intracranial germinoma presenting as Holmes' tremor: Importance of a tissue diagnosis. J Clin Neurosci. 2015 May. 22(5):911-3. [Medline].
Kim MC, Son BC, Miyagi Y, Kang JK. Vim thalamotomy for Holmes' tremor secondary to midbrain tumour. J Neurol Neurosurg Psychiatry. 2002 Oct. 73(4):453-5. [Medline]. [Full Text].
Jorsal T, Rørth M. Intracranial germ cell tumours. A review with special reference to endocrine manifestations. Acta Oncol. 2012 Jan. 51(1):3-9. [Medline].
Kim A, Ji L, Balmaceda C, Diez B, Kellie SJ, Dunkel IJ. The prognostic value of tumor markers in newly diagnosed patients with primary central nervous system germ cell tumors. Pediatr Blood Cancer. 2008 Dec. 51(6):768-73. [Medline].
Calaminus G, Bamberg M, Harms D, Jürgens H, Kortmann RD, Sörensen N, 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 Apr. 36(2):71-7. [Medline].
Shinoda J, Sakai N, Yano H, Hattori T, Ohkuma A, Sakaguchi H. Prognostic factors and therapeutic problems of primary intracranial choriocarcinoma/germ-cell tumors with high levels of HCG. J Neurooncol. 2004 Jan. 66(1-2):225-40. [Medline].
Shibamoto Y, Oda Y, Yamashita J, et al. The role of cerebrospinal fluid cytology in radiotherapy planning for intracranial germinoma. Int J Radiat Oncol Biol Phys. 1994 Jul 30. 29(5):1089-94. [Medline].
Shibamoto Y. Management of central nervous system germinoma: proposal for a modern strategy. Prog Neurol Surg. 2009. 23:119-29. [Medline].
Wu CC, Guo WY, Chang FC, Luo CB, Lee HJ, Chen YW, et al. MRI features of pediatric intracranial germ cell tumor subtypes. J Neurooncol. 2017 Aug. 134 (1):221-230. [Medline].
Wang Y, Zou L, Gao B. Intracranial germinoma: clinical and MRI findings in 56 patients. Childs Nerv Syst. 2010 Dec. 26 (12):1773-7. [Medline].
Okamoto K, Ito J, Ishikawa K, Morii K, Yamada M, Takahashi N, et al. Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia. Neuroradiology. 2002 May. 44 (5):389-94. [Medline].
Smith AB, Rushing EJ, Smirniotopoulos JG. From the archives of the AFIP: lesions of the pineal region: radiologic-pathologic correlation. Radiographics. 2010 Nov. 30 (7):2001-20. [Medline].
Dumrongpisutikul N, Intrapiromkul J, Yousem DM. Distinguishing between germinomas and pineal cell tumors on MR imaging. AJNR Am J Neuroradiol. 2012 Mar. 33 (3):550-5. [Medline]. [Full Text].
Awa R, Campos F, Arita K, Sugiyama K, Tominaga A, Kurisu K, et al. Neuroimaging diagnosis of pineal region tumors-quest for pathognomonic finding of germinoma. Neuroradiology. 2014 Jul. 56 (7):525-34. [Medline].
Takano M, Kinoshita Y, Sugiyama K, Kolakshyapati M, Takayasu T, Yonezawa U, et al. Detecting non-germinomatous germ cell tumor component by arterial spin labeling perfusion-weighted MR imaging in central nervous system germ cell tumor. Eur J Radiol. 2021 Mar. 136:109523. [Medline].
Okochi Y, Nihashi T, Fujii M, Kato K, Okada Y, Ando Y, et al. Clinical use of (11)C-methionine and (18)F-FDG-PET for germinoma in central nervous system. Ann Nucl Med. 2014 Feb. 28(2):94-102. [Medline]. [Full Text].
Tsouana E, Stoneham S, Fersht N, Kitchen N, Gaze M, Bomanji J, et al. Evaluation of treatment response using integrated 18F-labeled choline positron emission tomography/magnetic resonance imaging in adolescents with intracranial non-germinomatous germ cell tumours. Pediatr Blood Cancer. 2015 Apr 8. [Medline].
Frank Saran. Pineal Tumors: Germinomas and Non-germinomatous Germ Cell Tumor. Clinical Endocrine Oncology Second Edition. 2008 pp 310-317.
Friedman JA, Lynch JJ, Buckner JC, Scheithauer BW, Raffel C. Management of malignant pineal germ cell tumors with residual mature teratoma. Neurosurgery. 2001 Mar. 48(3):518-22; discussion 522-3. [Medline].
Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, et al. Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach. Pediatr Blood Cancer. 2004 Aug. 43(2):126-33. [Medline].
Kaur H, Singh D, Peereboom DM. Primary central nervous system germ cell tumors. Curr Treat Options Oncol. 2003 Dec. 4(6):491-8. [Medline].
Haas-Kogan DA, Missett BT, Wara WM, Donaldson SS, Lamborn KR, Prados MD, et al. Radiation therapy for intracranial germ cell tumors. Int J Radiat Oncol Biol Phys. 2003 Jun 1. 56(2):511-8. [Medline].
Matsatani M. Clinical Management of Primary Central Nervous System Germ Cell Tumors. Semin Oncol. 2004. 31:676-683.
Blakeley JO, Grossman SA. Management of pineal region tumors. Curr Treat Options Oncol. 2006 Nov. 7(6):505-16. [Medline].
Cho J, Choi JU, Kim DS, Suh CO. Low-dose craniospinal irradiation as a definitive treatment for intracranial germinoma. Radiother Oncol. 2009 Apr. 91(1):75-9. [Medline].
Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O. Combined treatment with chemotherapy and radiation therapy for intracranial germ cell tumors. Childs Nerv Syst. 1998 Jan-Feb. 14(1-2):59-62. [Medline].
Roberge D, Kun LE, Freeman CR. Intracranial germinoma: on whole-ventricular irradiation. Pediatr Blood Cancer. 2005 Apr. 44(4):358-62. [Medline].
Shikama N, Ogawa K, Tanaka S. Lack of benefit of spinal irradiation in the primary treatment of intracranial germinoma: a multiinstitutional, retrospective review of 180 patients. Cancer. 2005 Jul 1. 104(1):126-34.
Murray MJ, Bartels U, Nishikawa R, Fangusaro J, Matsutani M, Nicholson JC. Consensus on the management of intracranial germ-cell tumours. Lancet Oncol. 2015 Sep. 16 (9):e470-e477. [Medline].
Yan M, Laperriere N, Velec M, Bartels U, Ramaswamy V, Bouffet E, et al. Redefining Ventricular Target Volume in Germinoma: Is Inclusion of Temporal Horns Necessary?. Int J Radiat Oncol Biol Phys. 2019 Jul 15. 104 (4):852-858. [Medline].
Aoyama H. Radiation therapy for intracranial germ cell tumors. Prog Neurol Surg. 2009. 23:96-105. [Medline].
Bamberg M, Kortmann RD, Calaminus G, Becker G, Meisner C, Harms D. Radiation therapy for intracranial germinoma: results of the German cooperative prospective trials MAKEI 83/86/89. J Clin Oncol. 1999 Aug. 17(8):2585-92. [Medline].
Sawamura Y. Strategy of combined treatment of germ cell tumors. Prog Neurol Surg. 2009. 23:86-95. [Medline].
Shim KW, Kim TG, Suh CO, Cho JH, Yoo CJ, Choi JU, et al. Treatment failure in intracranial primary germinomas. Childs Nerv Syst. 2007 Oct. 23(10):1155-61. [Medline].
Yasuda K, Taguchi H, Sawamura Y, Ikeda J, Aoyama H, Fujieda K, et al. Low-dose craniospinal irradiation and ifosfamide, cisplatin and etoposide for non-metastatic embryonal tumors in the central nervous system. Jpn J Clin Oncol. 2008 Jul. 38(7):486-92. [Medline].
Schoenfeld GO, Amdur RJ, Schmalfuss IM, Morris CG, Keole SR, Mendenhall WM, et al. Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma. Int J Radiat Oncol Biol Phys. 2006 Jun 1. 65(2):481-5. [Medline].
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 Jul 15. 55(1):42-6. [Medline].
Kretschmar C, Kleinberg L, Greenberg M, Burger P, Holmes E, Wharam M. 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 Mar. 48(3):285-91. [Medline].
Cheng S, Kilday JP, Laperriere N, Janzen L, Drake J, Bouffet E, et al. Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation. J Neurooncol. 2016 Mar. 127 (1):173-80. [Medline].
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 Jun. 15(6):788-96. [Medline]. [Full Text].
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 Mar. 54(3):377-83. [Medline].
Douglas JG, Rockhill JK, Olson JM, Ellenbogen RG, Geyer JR. Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas. J Pediatr Hematol Oncol. 2006 Jan. 28(1):36-9. [Medline].
Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, 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 Mar 1. 22(5):846-53. [Medline].
Ogawa K, Toita T, Nakamura K, Uno T, Onishi H, Itami J. Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients. Cancer. 2003 Jul 15. 98(2):369-76. [Medline].
Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC, 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 May 15. 22(10):1934-43. [Medline].
Janmohamed S, Grossman AB, Metcalfe K, Lowe DG, Wood DF, Chew SL, et al. Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen. Clin Endocrinol (Oxf). 2002 Oct. 57(4):487-500. [Medline].
Peltier J, Vinchon M, Baroncini M, Kerdraon O, Dhellemmes P. Bifocal mixed germ-cell tumor with growing teratoma syndrome and metachronous mature metastases: case report. J Neurooncol. 2008 Oct. 90(1):111-5. [Medline].
Wang L, Yamaguchi S, Burstein MD, et al. Novel somatic and germline mutations in intracranial germ cell tumours. Nature. 2014 Jul 10. 511 (7508):241-5. [Medline]. [Full Text].

Media Gallery

MRI of the brain - T1 weighted-image- coronal view- showing a heterogeneously enhancing, multicystic mass in the suprasellar region
MRI of the brain - axial view- heterogeneous mass lesion measuring approximately 3.2 x 2.9 x 4.0 cm.
MRI of the brain - T1-weighted image - post-gadolinium sagittal view- A suprasellar lesion that severely compresses the optic chiasm encases the posterior aspect of the optic nerves bilaterally and causes superior displacement of the third ventricle, with significant compression of the brain stem.
Biopsy specimen from an intracranial germ cell tumor - Large tumor cells with large nuclei; prominent nucleoli; and abundant, clear cytoplasm (rich in glycogen) are noted among reactive inflammatory cells--lymphocytes and histiocytes. Elsewhere there are well-formed granulomas, a well-known phenomenon in germinomas, especially of the pineal region.

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Author

Amani A AlKofide, MD Chairman, Department of Pediatric Hematology/Oncology, Director, Neuro-Oncology Program and Lymphoma Program, King Faisal Specialist Hospital and Research Centre, Kingdom of Saudi Arabia

Amani A AlKofide, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, Histiocytosis Association, International Society of Paediatric Oncology, Riyadh Oncology Group, Saudi Pediatric Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Benjamin Movsas, MD

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology

Disclosure: Nothing to disclose.

Chief Editor

Herbert H Engelhard, III, MD, PhD, FACS, FAANS Affiliated Professor of Bioengineering, University of Illinois at Chicago

Herbert H Engelhard, III, MD, PhD, FACS, FAANS is a member of the following medical societies: American Association for Cancer Research, American Association of Neurological Surgeons, American College of Surgeons, American Medical Association, Congress of Neurological Surgeons, Illinois State Medical Society

Disclosure: Nothing to disclose.

Additional Contributors

Lodovico Balducci, MD Professor, Oncology Fellowship Director, Department of Internal Medicine, Division of Adult Oncology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida Morsani College of Medicine

Lodovico Balducci, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American College of Physicians, American Geriatrics Society, American Society of Hematology, New York Academy of Sciences, American Society of Clinical Oncology, Southern Society for Clinical Investigation, International Society for Experimental Hematology, American Federation for Clinical Research, American Society of Breast Disease

Disclosure: Nothing to disclose.

Sections Central Nervous System Germinoma
Overview
Presentation
DDx
Workup
Treatment
Medication
Media Gallery
Tables
References

Tumor type	β- HCG	AFP	PLAP	c-Kit
Germinoma - Pure	-	-	+/-	+
Germinoma with STGC*	+	-	+/-	+
Endodermal sinus tumor	-	+	+/-	-
Choriocarcinoma	+	-	+/-	-
Embryonal Carcinoma	-	-	+	-
Mixed Teratoma	+/-	+/-	+/-	+/-
Mature Teratoma	-	-	-	-
Immature teratoma	+/-	+/-	-	+/-
*Syncytiotrophoblastic giant cells

Central Nervous System Germinoma Clinical Presentation

History

Pineal region tumors

Suprasellar region tumors

Rare presentations

Physical Examination

References

Tables

Contributor Information and Disclosures

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