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==Overview==
==Overview==
The term germinoma most often refers to a tumor in the brain that has a histology identical to two other tumors: [[dysgerminoma]] in the [[ovary]] and [[seminoma]] in the [[testis]]. It may be [[benign]] or [[malignant]]. [[Germ cell tumors]] (GCTs) are classified as extragonadal if there is no evidence of a primary tumor in either the ovaries or the testes. Extragonadal GCTs typically arise in midline locations, and specific sites vary with age of the patient. In infants and young children, intracranial GCTs and sacrococcygeal [[teratomas]] are more common than other locations. In adults, the most common sites are the anterior [[retroperitoneum]], [[mediastinum]], and the [[pineal]] and [[suprasellar]] regions. [[Intracranial germ cell tumors]] are a heterogeneous group of lesions which occur in children and adults.<ref>Packer, Roger J., Bruce H. Cohen, and Kathleen Cooney. "Intracranial germ cell tumors." The Oncologist 5.4 (2000): 312-320.</ref> Germinoma may be classified according to World Health Organization into two groups: germinomas and nongerminomatous germ cell tumors. Based on the tumor markers secreted into the [[cerebrospinal fluid]] (CSF) and [[serum]], as well as by the presence of histochemical markers on tumor cells, intracranial germ cell tumors may be classified into either secreting  or non secreting [[tumors]]. Based on the prognosis of the tumor, intracranial germ cell tumors may be classified into either good, intermediate, or poor prognosis.<ref name="LouisOhgaki2007">{{cite journal|last1=Louis|first1=David N.|last2=Ohgaki|first2=Hiroko|last3=Wiestler|first3=Otmar D.|last4=Cavenee|first4=Webster K.|last5=Burger|first5=Peter C.|last6=Jouvet|first6=Anne|last7=Scheithauer|first7=Bernd W.|last8=Kleihues|first8=Paul|title=The 2007 WHO Classification of Tumours of the Central Nervous System|journal=Acta Neuropathologica|volume=114|issue=2|year=2007|pages=97–109|issn=0001-6322|doi=10.1007/s00401-007-0243-4}}</ref><ref name="pmid2991485">{{cite journal| author=Jennings MT, Gelman R, Hochberg F| title=Intracranial germ-cell tumors: natural history and pathogenesis. | journal=J Neurosurg | year= 1985 | volume= 63 | issue= 2 | pages= 155-67 | pmid=2991485 | doi=10.3171/jns.1985.63.2.0155 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2991485  }} </ref><ref name="pmid1848284">{{cite journal| author=Hoffman HJ, Otsubo H, Hendrick EB, Humphreys RP, Drake JM, Becker LE et al.| title=Intracranial germ-cell tumors in children. | journal=J Neurosurg | year= 1991 | volume= 74 | issue= 4 | pages= 545-51 | pmid=1848284 | doi=10.3171/jns.1991.74.4.0545 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1848284  }} </ref> On gross pathology, smooth and bosselated external surface, and soft, fleshy and either cream-colored, gray, pink or tan interior are characteristic findings of germinoma. On microscopic histopathological analysis, uniform cells that resemble [[primordial germ cells]], consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is [[eosinophilic]] are characteristic findings of germinoma. [[Genes]] involved in the pathogenesis of germinoma include the chromosomal imbalance comprises gains of 1p, 8p, and 12q and losses of 13q and 18q. duplication of the short arm of chromosome 12, loss of 1p and 6q and alterations in sex chromosomes in children, alterations of the ''p14'' gene, [[mutations]] of the ''c-kit'' gene, aberrations of ''CCND2'' (12P13), and ''RB1'', and and gain-of-function mutations of ''KIT''. The progression to germinoma usually involves the mutations of the ''KIT/RAS'' signalling or ''AKT1''/mtor pathways and cyclin/''CDK-RB-E2F'' pathway if ''CCND2'' (12P13) and ''RB1'' genes are aberrated.<ref name="pmid11005262">{{cite journal| author=Rickert CH, Simon R, Bergmann M, Dockhorn-Dworniczak B, Paulus W| title=Comparative genomic hybridization in pineal germ cell tumors. | journal=J Neuropathol Exp Neurol | year= 2000 | volume= 59 | issue= 9 | pages= 815-21 | pmid=11005262 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11005262  }} </ref><ref name="pmid16607373">{{cite journal| author=Schneider DT, Zahn S, Sievers S, Alemazkour K, Reifenberger G, Wiestler OD et al.| title=Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. | journal=Mod Pathol | year= 2006 | volume= 19 | issue= 6 | pages= 864-73 | pmid=16607373 | doi=10.1038/modpathol.3800607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16607373  }} </ref><ref name="pmid17285132">{{cite journal| author=Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP et al.| title=Malignant germ cell tumours of childhood: new associations of genomic imbalance. | journal=Br J Cancer | year= 2007 | volume= 96 | issue= 4 | pages= 667-76 | pmid=17285132 | doi=10.1038/sj.bjc.6603602 | pmc=PMC2360055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17285132  }} </ref><ref name="pmid19329861">{{cite journal| author=Sato K, Takeuchi H, Kubota T| title=Pathology of intracranial germ cell tumors. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 59-75 | pmid=19329861 | doi=10.1159/000210053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329861  }} </ref><ref name="pmid16572634">{{cite journal| author=Kamakura Y, Hasegawa M, Minamoto T, Yamashita J, Fujisawa H| title=C-kit gene mutation: common and widely distributed in intracranial germinomas. | journal=J Neurosurg | year= 2006 | volume= 104 | issue= 3 Suppl | pages= 173-80 | pmid=16572634 | doi=10.3171/ped.2006.104.3.173 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16572634  }} </ref><ref name="pmid15471556">{{cite journal| author=Sakuma Y, Sakurai S, Oguni S, Satoh M, Hironaka M, Saito K| title=c-kit gene mutations in intracranial germinomas. | journal=Cancer Sci | year= 2004 | volume= 95 | issue= 9 | pages= 716-20 | pmid=15471556 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15471556  }} </ref><ref name="pmid20178649">{{cite journal| author=Wang HW, Wu YH, Hsieh JY, Liang ML, Chao ME, Liu DJ et al.| title=Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations. | journal=BMC Genomics | year= 2010 | volume= 11 | issue=  | pages= 132 | pmid=20178649 | doi=10.1186/1471-2164-11-132 | pmc=PMC2837036 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20178649  }} </ref><ref name="pmid24249158">{{cite journal| author=Terashima K, Yu A, Chow WY, Hsu WC, Chen P, Wong S et al.| title=Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. | journal=Pediatr Blood Cancer | year= 2014 | volume= 61 | issue= 4 | pages= 593-600 | pmid=24249158 | doi=10.1002/pbc.24833 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24249158  }} </ref> The peak of germinoma occurs at ages 15-19 years: the median age at diagnosis is 10-12 years. CNS germ cell tumors commonly affects individuals between birth and 34 years of age. Males are more commonly affected with pineal germinona than females. The male to female ratio is approximately 5-22 to 1. Females are more commonly affected with suprasellar germinoma than males. The female to male ratio is approximately 1.3:1. Symptoms of germinoma include [[headache]], [[vomiting]], [[papilledema]], lethargy, somnolence, [[ataxia]], behavioral changes, decline in academic performance, paralysis of upward gaze, paralysis of convergence, [[diabetes insipidus]], delayed pubertal development, [[precocious puberty]], isolated [[growth hormone deficiency]], [[hypopituitarism]] (central hypothyroidism, adrenal insufficiency), decreased visual acuity from [[chiasmal]] or [[optic nerve]] compression, and visual field deficit (e.g, [[bitemporal hemianopsia]]). Presenting symptoms of patients with intracranial GCTs depend upon the location, size of the tumor, and the patient's age.<ref name="pmid23896184">{{cite journal| author=Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM| title=Delayed diagnosis in children with intracranial germ cell tumors. | journal=J Pediatr | year= 2013 | volume= 163 | issue= 5 | pages= 1448-53 | pmid=23896184 | doi=10.1016/j.jpeds.2013.06.024 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23896184  }} </ref><ref name="pmid10964999">{{cite journal| author=Packer RJ, Cohen BH, Cooney K, Coney K| title=Intracranial germ cell tumors. | journal=Oncologist | year= 2000 | volume= 5 | issue= 4 | pages= 312-20 | pmid=10964999 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10964999  }} </ref><ref name="pmid17502547">{{cite journal| author=Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, LaFond DA et al.| title=CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. | journal=Neurology | year= 2007 | volume= 68 | issue= 20 | pages= 1668-73 | pmid=17502547 | doi=10.1212/01.wnl.0000261908.36803.ac | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17502547  }} </ref> [[MRI]] of the brain and spine with and without gadolinium is the imaging modality of choice for germinoma. On MRI, intracranial GCTs appear isointense or hypointense on T1 sequences and hyperintense on T2 sequences.<ref name="radio"> Germinoma. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016</ref>
The term germinoma most often refers to a tumor in the brain that has a histology identical to two other tumors: [[dysgerminoma]] in the [[ovary]] and [[seminoma]] in the [[testis]]. It may be [[benign]] or [[malignant]]. [[Germ cell tumors]] (GCTs) are classified as extragonadal if there is no evidence of a primary tumor in either the ovaries or the testes. Extragonadal GCTs typically arise in midline locations, and specific sites vary with age of the patient. In infants and young children, intracranial GCTs and sacrococcygeal teratomas are more common than other locations. In adults, the most common sites are the anterior [[retroperitoneum]], [[mediastinum]], and the [[pineal]] and [[suprasellar]] regions. [[Intracranial germ cell tumors]] are a heterogeneous group of lesions which occur in children and adults.<ref>Packer, Roger J., Bruce H. Cohen, and Kathleen Cooney. "Intracranial germ cell tumors." The Oncologist 5.4 (2000): 312-320.</ref> Germinoma may be classified according to World Health Organization into two groups: germinomas and nongerminomatous germ cell tumors. Based on the tumor markers secreted into the [[cerebrospinal fluid]] (CSF) and [[serum]], as well as by the presence of histochemical markers on tumor cells, intracranial germ cell tumors may be classified into either secreting  or non secreting [[tumors]]. Based on the prognosis of the tumor, intracranial germ cell tumors may be classified into either good, intermediate, or poor prognosis.<ref name="LouisOhgaki2007">{{cite journal|last1=Louis|first1=David N.|last2=Ohgaki|first2=Hiroko|last3=Wiestler|first3=Otmar D.|last4=Cavenee|first4=Webster K.|last5=Burger|first5=Peter C.|last6=Jouvet|first6=Anne|last7=Scheithauer|first7=Bernd W.|last8=Kleihues|first8=Paul|title=The 2007 WHO Classification of Tumours of the Central Nervous System|journal=Acta Neuropathologica|volume=114|issue=2|year=2007|pages=97–109|issn=0001-6322|doi=10.1007/s00401-007-0243-4}}</ref><ref name="pmid2991485">{{cite journal| author=Jennings MT, Gelman R, Hochberg F| title=Intracranial germ-cell tumors: natural history and pathogenesis. | journal=J Neurosurg | year= 1985 | volume= 63 | issue= 2 | pages= 155-67 | pmid=2991485 | doi=10.3171/jns.1985.63.2.0155 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2991485  }} </ref><ref name="pmid1848284">{{cite journal| author=Hoffman HJ, Otsubo H, Hendrick EB, Humphreys RP, Drake JM, Becker LE et al.| title=Intracranial germ-cell tumors in children. | journal=J Neurosurg | year= 1991 | volume= 74 | issue= 4 | pages= 545-51 | pmid=1848284 | doi=10.3171/jns.1991.74.4.0545 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1848284  }} </ref> On gross pathology, smooth and bosselated external surface, and soft, fleshy and either cream-colored, gray, pink or tan interior are characteristic findings of germinoma.
On microscopic histopathological analysis, uniform cells that resemble primordial germ cells, consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic are characteristic findings of germinoma. Genes involved in the pathogenesis of germinoma include gains of 1p, 8p, and 12q and losses of 13q and 18q, duplication of the short arm of chromosome 12, loss of 1p and 6q, alterations in sex chromosomes in children, alterations of the ''p14'' gene, mutations of the ''c-kit'' gene, aberrations of ''CCND2'' (12P13), and ''RB1'', and gain-of-function mutations of ''KIT''. The progression to germinoma usually involves the mutations of the ''KIT/RAS'' signalling or ''AKT1''/mtor pathways and cyclin/''CDK-RB-E2F'' pathway if ''CCND2'' (12P13) and ''RB1'' genes are aberrated.<ref name="pmid11005262">{{cite journal| author=Rickert CH, Simon R, Bergmann M, Dockhorn-Dworniczak B, Paulus W| title=Comparative genomic hybridization in pineal germ cell tumors. | journal=J Neuropathol Exp Neurol | year= 2000 | volume= 59 | issue= 9 | pages= 815-21 | pmid=11005262 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11005262  }} </ref><ref name="pmid16607373">{{cite journal| author=Schneider DT, Zahn S, Sievers S, Alemazkour K, Reifenberger G, Wiestler OD et al.| title=Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. | journal=Mod Pathol | year= 2006 | volume= 19 | issue= 6 | pages= 864-73 | pmid=16607373 | doi=10.1038/modpathol.3800607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16607373  }} </ref><ref name="pmid17285132">{{cite journal| author=Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP et al.| title=Malignant germ cell tumours of childhood: new associations of genomic imbalance. | journal=Br J Cancer | year= 2007 | volume= 96 | issue= 4 | pages= 667-76 | pmid=17285132 | doi=10.1038/sj.bjc.6603602 | pmc=PMC2360055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17285132  }} </ref><ref name="pmid19329861">{{cite journal| author=Sato K, Takeuchi H, Kubota T| title=Pathology of intracranial germ cell tumors. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 59-75 | pmid=19329861 | doi=10.1159/000210053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329861  }} </ref><ref name="pmid16572634">{{cite journal| author=Kamakura Y, Hasegawa M, Minamoto T, Yamashita J, Fujisawa H| title=C-kit gene mutation: common and widely distributed in intracranial germinomas. | journal=J Neurosurg | year= 2006 | volume= 104 | issue= 3 Suppl | pages= 173-80 | pmid=16572634 | doi=10.3171/ped.2006.104.3.173 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16572634  }} </ref><ref name="pmid15471556">{{cite journal| author=Sakuma Y, Sakurai S, Oguni S, Satoh M, Hironaka M, Saito K| title=c-kit gene mutations in intracranial germinomas. | journal=Cancer Sci | year= 2004 | volume= 95 | issue= 9 | pages= 716-20 | pmid=15471556 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15471556  }} </ref><ref name="pmid20178649">{{cite journal| author=Wang HW, Wu YH, Hsieh JY, Liang ML, Chao ME, Liu DJ et al.| title=Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations. | journal=BMC Genomics | year= 2010 | volume= 11 | issue=  | pages= 132 | pmid=20178649 | doi=10.1186/1471-2164-11-132 | pmc=PMC2837036 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20178649  }} </ref><ref name="pmid24249158">{{cite journal| author=Terashima K, Yu A, Chow WY, Hsu WC, Chen P, Wong S et al.| title=Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. | journal=Pediatr Blood Cancer | year= 2014 | volume= 61 | issue= 4 | pages= 593-600 | pmid=24249158 | doi=10.1002/pbc.24833 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24249158  }} </ref>
The peak of germinoma occurs at ages 15-19 years: the median age at diagnosis is 10-12 years. CNS germ cell tumors commonly affects individuals between birth and 34 years of age. Males are more commonly affected with pineal germinoma than females. The male to female ratio is approximately 5-22 to 1. Females are more commonly affected with suprasellar germinoma than males. The female to male ratio is approximately 1.3:1. Symptoms of germinoma include [[headache]], [[vomiting]], [[papilledema]], lethargy, somnolence, [[ataxia]], behavioral changes, decline in academic performance, paralysis of upward gaze, paralysis of convergence, [[diabetes insipidus]], delayed pubertal development, [[precocious puberty]], isolated [[growth hormone deficiency]], [[hypopituitarism]] (central hypothyroidism, adrenal insufficiency), decreased visual acuity from chiasmal or [[optic nerve]] compression, and visual field deficit (e.g, [[bitemporal hemianopsia]]). Presenting symptoms of patients with intracranial GCTs depend upon the location, size of the tumor, and the patient's age.<ref name="pmid23896184">{{cite journal| author=Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM| title=Delayed diagnosis in children with intracranial germ cell tumors. | journal=J Pediatr | year= 2013 | volume= 163 | issue= 5 | pages= 1448-53 | pmid=23896184 | doi=10.1016/j.jpeds.2013.06.024 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23896184  }} </ref><ref name="pmid10964999">{{cite journal| author=Packer RJ, Cohen BH, Cooney K, Coney K| title=Intracranial germ cell tumors. | journal=Oncologist | year= 2000 | volume= 5 | issue= 4 | pages= 312-20 | pmid=10964999 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10964999  }} </ref><ref name="pmid17502547">{{cite journal| author=Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, LaFond DA et al.| title=CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. | journal=Neurology | year= 2007 | volume= 68 | issue= 20 | pages= 1668-73 | pmid=17502547 | doi=10.1212/01.wnl.0000261908.36803.ac | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17502547  }} </ref> [[MRI]] of the brain and spine with and without gadolinium is the imaging modality of choice for germinoma. On MRI, intracranial GCTs appear isointense or hypointense on T1 sequences and hyperintense on T2 sequences.<ref name="radio"> Germinoma. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016</ref> The predominant therapy for CNS germ cell tumors is [[radiation therapy]]. Adjunctive [[chemotherapy]] and [[surgery]] may be required.<ref name="pmid14990640">{{cite journal| author=Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L et al.| title=Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. | journal=J Clin Oncol | year= 2004 | volume= 22 | issue= 5 | pages= 846-53 | pmid=14990640 | doi=10.1200/JCO.2004.07.006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14990640  }} </ref><ref name="pmid12872359">{{cite journal| author=Ogawa K, Toita T, Nakamura K, Uno T, Onishi H, Itami J et al.| title=Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients. | journal=Cancer | year= 2003 | volume= 98 | issue= 2 | pages= 369-76 | pmid=12872359 | doi=10.1002/cncr.11495 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12872359  }} </ref><ref name="pmid15102352">{{cite journal| author=Balmaceda C, Finlay J| title=Current advances in the diagnosis and management of intracranial germ cell tumors. | journal=Curr Neurol Neurosci Rep | year= 2004 | volume= 4 | issue= 3 | pages= 253-62 | pmid=15102352 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15102352  }} </ref><ref name="pmid15143087">{{cite journal| author=Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC et al.| title=Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. | journal=J Clin Oncol | year= 2004 | volume= 22 | issue= 10 | pages= 1934-43 | pmid=15143087 | doi=10.1200/JCO.2004.11.053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15143087  }} </ref> The feasibility of surgery depends on the type of the intracranial germ cell tumor at diagnosis. Surgery is not the first-line treatment option for patients with germ cell tumors. Surgery is usually reserved for patients with either NGGCTs, or in patients who have had an incomplete response to initial chemotherapy, and in patients with "growing teratoma syndrome".<ref name="pmid18586924">{{cite journal| author=Echevarría ME, Fangusaro J, Goldman S| title=Pediatric central nervous system germ cell tumors: a review. | journal=Oncologist | year= 2008 | volume= 13 | issue= 6 | pages= 690-9 | pmid=18586924 | doi=10.1634/theoncologist.2008-0037 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18586924  }} </ref><ref name="pmid14585229">{{cite journal| author=Kaur H, Singh D, Peereboom DM| title=Primary central nervous system germ cell tumors. | journal=Curr Treat Options Oncol | year= 2003 | volume= 4 | issue= 6 | pages= 491-8 | pmid=14585229 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14585229  }} </ref><ref name="pmid23896184">{{cite journal| author=Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM| title=Delayed diagnosis in children with intracranial germ cell tumors. | journal=J Pediatr | year= 2013 | volume= 163 | issue= 5 | pages= 1448-53 | pmid=23896184 | doi=10.1016/j.jpeds.2013.06.024 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23896184  }} </ref><ref name="pmid19329866">{{cite journal| author=Shibamoto Y| title=Management of central nervous system germinoma: proposal for a modern strategy. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 119-29 | pmid=19329866 | doi=10.1159/000210058 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329866  }} </ref><ref name="pmid19329863">{{cite journal| author=Sawamura Y| title=Strategy of combined treatment of germ cell tumors. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 86-95 | pmid=19329863 | doi=10.1159/000210055 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329863  }} </ref><ref name="pmid16598761">{{cite journal| author=Kretschmar C, Kleinberg L, Greenberg M, Burger P, Holmes E, Wharam M| title=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. | journal=Pediatr Blood Cancer | year= 2007 | volume= 48 | issue= 3 | pages= 285-91 | pmid=16598761 | doi=10.1002/pbc.20815 | pmc=PMC4086720 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16598761  }} </ref><ref name="pmid18421722">{{cite journal| author=Finlay J, da Silva NS, Lavey R, Bouffet E, Kellie SJ, Shaw E et al.| title=The management of patients with primary central nervous system (CNS) germinoma: current controversies requiring resolution. | journal=Pediatr Blood Cancer | year= 2008 | volume= 51 | issue= 2 | pages= 313-6 | pmid=18421722 | doi=10.1002/pbc.21555 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18421722  }} </ref><ref name="pmid12354131">{{cite journal| author=Janmohamed S, Grossman AB, Metcalfe K, Lowe DG, Wood DF, Chew SL et al.| title=Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen. | journal=Clin Endocrinol (Oxf) | year= 2002 | volume= 57 | issue= 4 | pages= 487-500 | pmid=12354131 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12354131  }} </ref><ref name="pmid14990640">{{cite journal| author=Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L et al.| title=Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. | journal=J Clin Oncol | year= 2004 | volume= 22 | issue= 5 | pages= 846-53 | pmid=14990640 | doi=10.1200/JCO.2004.07.006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14990640  }} </ref><ref name="SaranPeoples2008">{{cite journal|last1=Saran|first1=Frank|last2=Peoples|first2=Sharon|title=Pineal Tumors: Germinomas and Non-Germinomatous Germ Cell Tumors|year=2008|pages=310–317|doi=10.1002/9781444300222.ch41}}</ref><ref name="pmid18574668">{{cite journal| author=Peltier J, Vinchon M, Baroncini M, Kerdraon O, Dhellemmes P| title=Bifocal mixed germ-cell tumor with growing teratoma syndrome and metachronous mature metastases: case report. | journal=J Neurooncol | year= 2008 | volume= 90 | issue= 1 | pages= 111-5 | pmid=18574668 | doi=10.1007/s11060-008-9640-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18574668  }} </ref><ref name="pmid11270541">{{cite journal| author=Friedman JA, Lynch JJ, Buckner JC, Scheithauer BW, Raffel C| title=Management of malignant pineal germ cell tumors with residual mature teratoma. | journal=Neurosurgery | year= 2001 | volume= 48 | issue= 3 | pages= 518-22; discussion 522-3 | pmid=11270541 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11270541  }} </ref>


==Historical Perspective==
==Historical Perspective==
==Classification==
==Classification==
Germinoma may be classified according to World Health Organization into two groups: germinomas and nongerminomatous germ cell tumors. Based on the tumor markers secreted into the cerebrospinal fluid (CSF) and serum, as well as by the presence of histochemical markers on tumor cells, intracranial germ cell tumors may be classified into either secreting  or nonsecreting tumors. Based on the prognosis of the tumor, intracranial germ cell tumors may be classified into either good, intermediate, or poor prognosis.<ref name="LouisOhgaki2007">{{cite journal|last1=Louis|first1=David N.|last2=Ohgaki|first2=Hiroko|last3=Wiestler|first3=Otmar D.|last4=Cavenee|first4=Webster K.|last5=Burger|first5=Peter C.|last6=Jouvet|first6=Anne|last7=Scheithauer|first7=Bernd W.|last8=Kleihues|first8=Paul|title=The 2007 WHO Classification of Tumours of the Central Nervous System|journal=Acta Neuropathologica|volume=114|issue=2|year=2007|pages=97–109|issn=0001-6322|doi=10.1007/s00401-007-0243-4}}</ref><ref name="pmid2991485">{{cite journal| author=Jennings MT, Gelman R, Hochberg F| title=Intracranial germ-cell tumors: natural history and pathogenesis. | journal=J Neurosurg | year= 1985 | volume= 63 | issue= 2 | pages= 155-67 | pmid=2991485 | doi=10.3171/jns.1985.63.2.0155 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2991485  }} </ref><ref name="pmid1848284">{{cite journal| author=Hoffman HJ, Otsubo H, Hendrick EB, Humphreys RP, Drake JM, Becker LE et al.| title=Intracranial germ-cell tumors in children. | journal=J Neurosurg | year= 1991 | volume= 74 | issue= 4 | pages= 545-51 | pmid=1848284 | doi=10.3171/jns.1991.74.4.0545 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1848284  }} </ref>
Germinoma may be classified according to World Health Organization into two groups: [[germinomas]] and nongerminomatous germ cell [[tumors]]. Based on the tumor markers secreted into the [[cerebrospinal fluid]] (CSF) and [[serum]], as well as by the presence of histochemical markers on tumor cells, intracranial germ cell tumors may be classified into either secreting  or non secreting tumors. Based on the prognosis of the tumor, intracranial germ cell tumors may be classified into either good, intermediate, or poor prognosis.<ref name="LouisOhgaki2007">{{cite journal|last1=Louis|first1=David N.|last2=Ohgaki|first2=Hiroko|last3=Wiestler|first3=Otmar D.|last4=Cavenee|first4=Webster K.|last5=Burger|first5=Peter C.|last6=Jouvet|first6=Anne|last7=Scheithauer|first7=Bernd W.|last8=Kleihues|first8=Paul|title=The 2007 WHO Classification of Tumours of the Central Nervous System|journal=Acta Neuropathologica|volume=114|issue=2|year=2007|pages=97–109|issn=0001-6322|doi=10.1007/s00401-007-0243-4}}</ref><ref name="pmid2991485">{{cite journal| author=Jennings MT, Gelman R, Hochberg F| title=Intracranial germ-cell tumors: natural history and pathogenesis. | journal=J Neurosurg | year= 1985 | volume= 63 | issue= 2 | pages= 155-67 | pmid=2991485 | doi=10.3171/jns.1985.63.2.0155 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2991485  }} </ref><ref name="pmid1848284">{{cite journal| author=Hoffman HJ, Otsubo H, Hendrick EB, Humphreys RP, Drake JM, Becker LE et al.| title=Intracranial germ-cell tumors in children. | journal=J Neurosurg | year= 1991 | volume= 74 | issue= 4 | pages= 545-51 | pmid=1848284 | doi=10.3171/jns.1991.74.4.0545 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1848284  }} </ref>


==Pathophysiology==
==Pathophysiology==
On gross pathology, smooth and bosselated external surface, and soft, fleshy and either cream-colored, gray, pink or tan interior are characteristic findings of germinoma.
On microscopic histopathological analysis, uniform cells that resemble [[primordial germ cells]], consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic are characteristic findings of germinoma. Genes involved in the pathogenesis of germinoma include gains of 1p, 8p, and 12q and losses of 13q and 18q, duplication of the short arm of chromosome 12, loss of 1p and 6q, alterations in sex chromosomes in children, alterations of the ''p14'' gene, mutations of the ''c-kit'' gene, aberrations of ''CCND2'' (12P13), and ''RB1'', and gain-of-function mutations of ''KIT''. The progression to germinoma usually involves the mutations of the ''KIT/RAS'' signalling or ''AKT1''/mtor pathways and cyclin/''CDK-RB-E2F'' pathway if ''CCND2'' (12P13) and ''RB1'' genes are aberrated.<ref name="pmid11005262">{{cite journal| author=Rickert CH, Simon R, Bergmann M, Dockhorn-Dworniczak B, Paulus W| title=Comparative genomic hybridization in pineal germ cell tumors. | journal=J Neuropathol Exp Neurol | year= 2000 | volume= 59 | issue= 9 | pages= 815-21 | pmid=11005262 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11005262  }} </ref><ref name="pmid16607373">{{cite journal| author=Schneider DT, Zahn S, Sievers S, Alemazkour K, Reifenberger G, Wiestler OD et al.| title=Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. | journal=Mod Pathol | year= 2006 | volume= 19 | issue= 6 | pages= 864-73 | pmid=16607373 | doi=10.1038/modpathol.3800607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16607373  }} </ref><ref name="pmid17285132">{{cite journal| author=Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP et al.| title=Malignant germ cell tumours of childhood: new associations of genomic imbalance. | journal=Br J Cancer | year= 2007 | volume= 96 | issue= 4 | pages= 667-76 | pmid=17285132 | doi=10.1038/sj.bjc.6603602 | pmc=PMC2360055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17285132  }} </ref><ref name="pmid19329861">{{cite journal| author=Sato K, Takeuchi H, Kubota T| title=Pathology of intracranial germ cell tumors. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 59-75 | pmid=19329861 | doi=10.1159/000210053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329861  }} </ref><ref name="pmid16572634">{{cite journal| author=Kamakura Y, Hasegawa M, Minamoto T, Yamashita J, Fujisawa H| title=C-kit gene mutation: common and widely distributed in intracranial germinomas. | journal=J Neurosurg | year= 2006 | volume= 104 | issue= 3 Suppl | pages= 173-80 | pmid=16572634 | doi=10.3171/ped.2006.104.3.173 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16572634  }} </ref><ref name="pmid15471556">{{cite journal| author=Sakuma Y, Sakurai S, Oguni S, Satoh M, Hironaka M, Saito K| title=c-kit gene mutations in intracranial germinomas. | journal=Cancer Sci | year= 2004 | volume= 95 | issue= 9 | pages= 716-20 | pmid=15471556 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15471556  }} </ref><ref name="pmid20178649">{{cite journal| author=Wang HW, Wu YH, Hsieh JY, Liang ML, Chao ME, Liu DJ et al.| title=Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations. | journal=BMC Genomics | year= 2010 | volume= 11 | issue=  | pages= 132 | pmid=20178649 | doi=10.1186/1471-2164-11-132 | pmc=PMC2837036 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20178649  }} </ref><ref name="pmid24249158">{{cite journal| author=Terashima K, Yu A, Chow WY, Hsu WC, Chen P, Wong S et al.| title=Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. | journal=Pediatr Blood Cancer | year= 2014 | volume= 61 | issue= 4 | pages= 593-600 | pmid=24249158 | doi=10.1002/pbc.24833 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24249158  }} </ref>
On microscopic histopathological analysis, uniform cells that resemble primordial germ cells, consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic are characteristic findings of germinoma. Genes involved in the pathogenesis of germinoma include the chromosomal imbalance comprises gains of 1p, 8p, and 12q and losses of 13q and 18q. duplication of the short arm of chromosome 12, loss of 1p and 6q and alterations in sex chromosomes in children, alterations of the p14 gene, mutations of the c-kit gene, aberrations of CCND2 (12P13), and RB1, and and gain-of-function mutations of KIT. The progression to germinoma usually involves the mutations of the KIT/RAS signalling or AKT1/mtor pathways and cyclin/CDK-RB-E2F pathway if CCND2 (12P13) and RB1 genes are aberrated.<ref name="pmid11005262">{{cite journal| author=Rickert CH, Simon R, Bergmann M, Dockhorn-Dworniczak B, Paulus W| title=Comparative genomic hybridization in pineal germ cell tumors. | journal=J Neuropathol Exp Neurol | year= 2000 | volume= 59 | issue= 9 | pages= 815-21 | pmid=11005262 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11005262  }} </ref><ref name="pmid16607373">{{cite journal| author=Schneider DT, Zahn S, Sievers S, Alemazkour K, Reifenberger G, Wiestler OD et al.| title=Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. | journal=Mod Pathol | year= 2006 | volume= 19 | issue= 6 | pages= 864-73 | pmid=16607373 | doi=10.1038/modpathol.3800607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16607373  }} </ref><ref name="pmid17285132">{{cite journal| author=Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP et al.| title=Malignant germ cell tumours of childhood: new associations of genomic imbalance. | journal=Br J Cancer | year= 2007 | volume= 96 | issue= 4 | pages= 667-76 | pmid=17285132 | doi=10.1038/sj.bjc.6603602 | pmc=PMC2360055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17285132  }} </ref><ref name="pmid19329861">{{cite journal| author=Sato K, Takeuchi H, Kubota T| title=Pathology of intracranial germ cell tumors. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 59-75 | pmid=19329861 | doi=10.1159/000210053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329861  }} </ref><ref name="pmid16572634">{{cite journal| author=Kamakura Y, Hasegawa M, Minamoto T, Yamashita J, Fujisawa H| title=C-kit gene mutation: common and widely distributed in intracranial germinomas. | journal=J Neurosurg | year= 2006 | volume= 104 | issue= 3 Suppl | pages= 173-80 | pmid=16572634 | doi=10.3171/ped.2006.104.3.173 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16572634  }} </ref><ref name="pmid15471556">{{cite journal| author=Sakuma Y, Sakurai S, Oguni S, Satoh M, Hironaka M, Saito K| title=c-kit gene mutations in intracranial germinomas. | journal=Cancer Sci | year= 2004 | volume= 95 | issue= 9 | pages= 716-20 | pmid=15471556 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15471556  }} </ref><ref name="pmid20178649">{{cite journal| author=Wang HW, Wu YH, Hsieh JY, Liang ML, Chao ME, Liu DJ et al.| title=Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations. | journal=BMC Genomics | year= 2010 | volume= 11 | issue=  | pages= 132 | pmid=20178649 | doi=10.1186/1471-2164-11-132 | pmc=PMC2837036 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20178649  }} </ref><ref name="pmid24249158">{{cite journal| author=Terashima K, Yu A, Chow WY, Hsu WC, Chen P, Wong S et al.| title=Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. | journal=Pediatr Blood Cancer | year= 2014 | volume= 61 | issue= 4 | pages= 593-600 | pmid=24249158 | doi=10.1002/pbc.24833 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24249158  }} </ref>


==Causes==
==Causes==
There are no established causes for germinoma. However, several theories have been postulated to define the cause of germ cell tumors.  
There are no established causes for germinoma. However, several theories have been postulated to define the cause of germ cell tumors.  
GCTs arise from primordial germ cells that migrate to the germinal ridges in the developing embryo. The process of migration appears to be under the control of complex molecular events. Alteration in any of these molecular pathways may give rise to GCTs. Rather than laterally to genital ridges, some primordial germ cells that have left the yolk sac endoderm migrate aberrantly cranially towards the diencephalic midline structures.<ref name="pmid18586924">{{cite journal| author=Echevarría ME, Fangusaro J, Goldman S| title=Pediatric central nervous system germ cell tumors: a review. | journal=Oncologist | year= 2008 | volume= 13 | issue= 6 | pages= 690-9 | pmid=18586924 | doi=10.1634/theoncologist.2008-0037 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18586924  }} </ref><ref name="pmid15971448">{{cite journal| author=Jubran RF, Finlay J| title=Central nervous system germ cell tumors: controversies in diagnosis and treatment. | journal=Oncology (Williston Park) | year= 2005 | volume= 19 | issue= 6 | pages= 705-11; discussion 711-2, 715-7, 721 | pmid=15971448 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15971448  }} </ref><ref name="pmid17285132">{{cite journal| author=Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP et al.| title=Malignant germ cell tumours of childhood: new associations of genomic imbalance. | journal=Br J Cancer | year= 2007 | volume= 96 | issue= 4 | pages= 667-76 | pmid=17285132 | doi=10.1038/sj.bjc.6603602 | pmc=PMC2360055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17285132  }} </ref><ref name="pmid19329861">{{cite journal| author=Sato K, Takeuchi H, Kubota T| title=Pathology of intracranial germ cell tumors. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 59-75 | pmid=19329861 | doi=10.1159/000210053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329861  }} </ref><ref name="pmid1760220">{{cite journal| author=Pereda J, Motta PM| title=A unique fibrillar coat on the surface of migrating human primordial germ cells. | journal=Arch Histol Cytol | year= 1991 | volume= 54 | issue= 4 | pages= 419-25 | pmid=1760220 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1760220  }} </ref><ref name="pmid1811953">{{cite journal| author=Godin I, Wylie CC| title=TGF beta 1 inhibits proliferation and has a chemotropic effect on mouse primordial germ cells in culture. | journal=Development | year= 1991 | volume= 113 | issue= 4 | pages= 1451-7 | pmid=1811953 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1811953  }} </ref><ref name="pmid2039390">{{cite journal| author=Horowitz MB, Hall WA| title=Central nervous system germinomas. A review. | journal=Arch Neurol | year= 1991 | volume= 48 | issue= 6 | pages= 652-7 | pmid=2039390 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2039390  }} </ref> Biopsy may be helpful in the diagnosis of germinoma. Findings on biopsy diagnostic of germinoma include undifferentiated, uniform large cells with abundant glycogen-rich cytoplasm arranged in nests separated by bands of connective tissue along trophoblastic lines.<ref name="pmid19329866">{{cite journal| author=Shibamoto Y| title=Management of central nervous system germinoma: proposal for a modern strategy. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 119-29 | pmid=19329866 | doi=10.1159/000210058 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329866  }} </ref>
GCTs arise from [[primordial germ cells]] that migrate to the germinal ridges in the developing embryo. The process of migration appears to be under the control of complex molecular events. Alteration in any of these molecular pathways may give rise to GCTs. Rather than laterally to genital ridges, some primordial germ cells that have left the yolk sac endoderm migrate aberrantly cranially towards the [[diencephalic]] midline structures.<ref name="pmid18586924">{{cite journal| author=Echevarría ME, Fangusaro J, Goldman S| title=Pediatric central nervous system germ cell tumors: a review. | journal=Oncologist | year= 2008 | volume= 13 | issue= 6 | pages= 690-9 | pmid=18586924 | doi=10.1634/theoncologist.2008-0037 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18586924  }} </ref><ref name="pmid15971448">{{cite journal| author=Jubran RF, Finlay J| title=Central nervous system germ cell tumors: controversies in diagnosis and treatment. | journal=Oncology (Williston Park) | year= 2005 | volume= 19 | issue= 6 | pages= 705-11; discussion 711-2, 715-7, 721 | pmid=15971448 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15971448  }} </ref><ref name="pmid17285132">{{cite journal| author=Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP et al.| title=Malignant germ cell tumours of childhood: new associations of genomic imbalance. | journal=Br J Cancer | year= 2007 | volume= 96 | issue= 4 | pages= 667-76 | pmid=17285132 | doi=10.1038/sj.bjc.6603602 | pmc=PMC2360055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17285132  }} </ref><ref name="pmid19329861">{{cite journal| author=Sato K, Takeuchi H, Kubota T| title=Pathology of intracranial germ cell tumors. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 59-75 | pmid=19329861 | doi=10.1159/000210053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329861  }} </ref><ref name="pmid1760220">{{cite journal| author=Pereda J, Motta PM| title=A unique fibrillar coat on the surface of migrating human primordial germ cells. | journal=Arch Histol Cytol | year= 1991 | volume= 54 | issue= 4 | pages= 419-25 | pmid=1760220 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1760220  }} </ref><ref name="pmid1811953">{{cite journal| author=Godin I, Wylie CC| title=TGF beta 1 inhibits proliferation and has a chemotropic effect on mouse primordial germ cells in culture. | journal=Development | year= 1991 | volume= 113 | issue= 4 | pages= 1451-7 | pmid=1811953 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1811953  }} </ref><ref name="pmid2039390">{{cite journal| author=Horowitz MB, Hall WA| title=Central nervous system germinomas. A review. | journal=Arch Neurol | year= 1991 | volume= 48 | issue= 6 | pages= 652-7 | pmid=2039390 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2039390  }} </ref> Biopsy may be helpful in the diagnosis of germinoma. Findings on biopsy diagnostic of germinoma include undifferentiated, uniform large cells with abundant glycogen-rich cytoplasm arranged in nests separated by bands of connective tissue along trophoblastic lines.<ref name="pmid19329866">{{cite journal| author=Shibamoto Y| title=Management of central nervous system germinoma: proposal for a modern strategy. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 119-29 | pmid=19329866 | doi=10.1159/000210058 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329866  }} </ref>
==Epidemiology and Demographics==
==Epidemiology and Demographics==
The peak of germinoma occurs at ages 15-19 years: the median age at diagnosis is 10-12 years. CNS germ cell tumors commonly affects individuals between birth and 34 years of age. Males are more commonly affected with pineal germinoma than females. The male to female ratio is approximately 5-22 to 1. Females are more commonly affected with suprasellar germinoma than males. The female to male ratio is approximately 1.3:1.
The peak of germinoma occurs at ages 15-19 years: the median age at diagnosis is 10-12 years. CNS germ cell tumors commonly affects individuals between birth and 34 years of age. Males are more commonly affected with pineal germinoma than females. The male to female ratio is approximately 5-22 to 1. Females are more commonly affected with suprasellar germinoma than males. The female to male ratio is approximately 1.3:1.
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==Differential Diagnosis==
==Differential Diagnosis==
Germinoma must be differentiated from other lesions in the pineal and suprasellar region, such as glial tumors which include astrocytomas and gangliomas, granular cell tumor, hamartomas, xanthogranuloma, meningiomas, colloid cysts, craniopharyngioma, cysticercosis, metastatic cancer with unknown primary site, pineal tumors, and pituitary macroadenomas.<ref name="radio"> Germ cell tumors. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016</ref>  
Germinoma must be differentiated from other lesions in the pineal and suprasellar region, such as glial tumors which include [[astrocytomas]] and gangliomas, [[granular cell tumor]], [[hamartomas]], [[xanthogranuloma]], [[meningiomas]], [[colloid cysts]], [[craniopharyngioma]], [[cysticercosis]], metastatic cancer with unknown primary site, pineal tumors, and pituitary macroadenomas.<ref name="radio"> Germ cell tumors. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016</ref>
 
==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
If left untreated, more than 50% of patients may continue to suffer from endocrine abnormalities such as growth hormone deficiency, growth retardation, hypopituitarism, and hypothyroidism, and may require lifelong hormonal replacement therapy. Common complications of germinoma include secondary cancers such as acute myeloid leukemia and radiation-induced brain neoplasms. Prognosis is generally excellent for germinomas, and the 5-year survival rate of patients with germinoma is approximately 70-90%.
If left untreated, more than 50% of patients may continue to suffer from endocrine abnormalities such as [[growth hormone deficiency]], [[growth retardation]], [[hypopituitarism]], and [[hypothyroidism]], and may require lifelong hormonal replacement therapy. Common complications of germinoma include secondary cancers such as [[acute myeloid leukemia]] and radiation-induced brain neoplasms. Prognosis is generally excellent for germinomas, and the 5-year survival rate of patients with germinoma is approximately 70-90%. However, prognosis in general depends on the histological diagnosis and staging of the extent of disease.
However, prognosis in general depends on the histological diagnosis and staging of the extent of disease.
 
==Diagnosis==
==Diagnosis==
===Staging===
===Staging===
There is no established system for the staging of germ cell tumors, and most investigators utilize the TM system employed for staging medulloblastomas. Predominantly because of their midline location, staging for the size of the tumor at the time of diagnosis or after surgery (T-stage evaluation), has not been routinely employed in germ cell tumors.
There is no established system for the staging of germ cell tumors, and most investigators utilize the TM system employed for staging medulloblastomas. Predominantly because of their midline location, staging for the size of the tumor at the time of diagnosis or after surgery (T-stage evaluation), has not been routinely employed in germ cell tumors.
===History and Symptoms===
===History and Symptoms===
Symptoms of germinoma include headache, vomiting, papilledema, lethargy, somnolence, ataxia, behavioral changes, decline in academic performance, paralysis of upward gaze,,paralysis of convergence, diabetes insipidus, delayed pubertal development, precocious puberty, isolated growth hormone deficiency, hypopituitarism (central hypothyroidism, adrenal insufficiency), decreased visual acuity from chiasmic or optic nerve compression, and visual field deficit (e.g, bitemporal hemianopsia). Presenting symptoms of patients with intracranial GCTs depend upon the location, size of the tumor, and the patient's age.<ref name="pmid23896184">{{cite journal| author=Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM| title=Delayed diagnosis in children with intracranial germ cell tumors. | journal=J Pediatr | year= 2013 | volume= 163 | issue= 5 | pages= 1448-53 | pmid=23896184 | doi=10.1016/j.jpeds.2013.06.024 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23896184  }} </ref><ref name="pmid10964999">{{cite journal| author=Packer RJ, Cohen BH, Cooney K, Coney K| title=Intracranial germ cell tumors. | journal=Oncologist | year= 2000 | volume= 5 | issue= 4 | pages= 312-20 | pmid=10964999 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10964999  }} </ref><ref name="pmid17502547">{{cite journal| author=Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, LaFond DA et al.| title=CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. | journal=Neurology | year= 2007 | volume= 68 | issue= 20 | pages= 1668-73 | pmid=17502547 | doi=10.1212/01.wnl.0000261908.36803.ac | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17502547  }} </ref>
Symptoms of germinoma include [[headache]], [[vomiting]], [[papilledema]], lethargy, [[somnolence]], [[ataxia]], behavioral changes, decline in academic performance, paralysis of upward gaze, paralysis of convergence, [[diabetes insipidus]], delayed pubertal development, [[precocious puberty]], isolated [[growth hormone deficiency]], [[hypopituitarism]] (central [[hypothyroidism]], [[adrenal insufficiency]]), decreased visual acuity from chiasmal or [[optic nerve]] compression, and visual field deficit (e.g, bitemporal hemianopsia). Presenting symptoms of patients with intracranial GCTs depend upon the location, size of the tumor, and the patient's age.<ref name="pmid23896184">{{cite journal| author=Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM| title=Delayed diagnosis in children with intracranial germ cell tumors. | journal=J Pediatr | year= 2013 | volume= 163 | issue= 5 | pages= 1448-53 | pmid=23896184 | doi=10.1016/j.jpeds.2013.06.024 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23896184  }} </ref><ref name="pmid10964999">{{cite journal| author=Packer RJ, Cohen BH, Cooney K, Coney K| title=Intracranial germ cell tumors. | journal=Oncologist | year= 2000 | volume= 5 | issue= 4 | pages= 312-20 | pmid=10964999 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10964999  }} </ref><ref name="pmid17502547">{{cite journal| author=Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, LaFond DA et al.| title=CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. | journal=Neurology | year= 2007 | volume= 68 | issue= 20 | pages= 1668-73 | pmid=17502547 | doi=10.1212/01.wnl.0000261908.36803.ac | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17502547  }} </ref>


===Physical Examination===
===Physical Examination===
Common physical examination findings of germinoma include paralysis of upward gaze, pupils nonreactive to light perception and accommodation or pupils which react better to accommodation than light, nystagmus, failure of convergence, lid retraction, papilledema, ataxia, and neurologic examination may be abnormal depending on the location of the tumor.
Common physical examination findings of germinoma include paralysis of upward gaze, pupils nonreactive to light perception and accommodation or pupils which react better to accommodation than light, [[nystagmus]], failure of convergence, lid retraction, [[papilledema]], [[ataxia]], and neurologic examination may be abnormal depending on the location of the tumor.
==Laboratory Findings==
===Laboratory Findings===
An elevated concentration of AFP and beta-hCG in the serum and CSF, and CSF cytology to detect malignant cells is diagnostic of intracranial germ cell tumors. In patients in whom endoscopic biopsy is not considered possible, detection of elevated tumor markers may be sufficient for diagnosis.  
An elevated concentration of AFP and beta-hCG in the [[serum]] and [[CSF]], and CSF cytology to detect [[malignant]] cells is diagnostic of intracranial germ cell tumors. In patients in whom endoscopic [[biopsy]] is not considered possible, detection of elevated tumor markers may be sufficient for diagnosis.  


===Chest X Ray===
===Chest X Ray===
Chest x-rays may be performed to detect metastases of germinoma to the [[lungs]].
Chest x-rays may be performed to detect metastases of germinoma to the [[lungs]].
===CT===
===CT===
Head and neck CT scan may be diagnostic of germinoma. Findings on CT scan suggestive of germinoma include hyperdensity compared to adjacent brain, pituitary stalk enhancement and thickening, and presence of calcification in the pineal region in the pediatric population.<ref name="radio"> Germinoma. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016</ref>
Head and neck CT scan may be diagnostic of germinoma. Findings on CT scan suggestive of germinoma include hyperdensity compared to adjacent brain, [[pituitary stalk]] enhancement and thickening, and presence of [[calcification]] in the pineal region in the pediatric population.<ref name="radio"> Germinoma. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016</ref>
===MRI===
===MRI===
MRI of the brain and spine with and without gadolinium is the imaging modality of choice for germinoma. On MRI, intracranial GCTs appear isointense or hypointense on T1 sequences and hyperintense on T2 sequences.<ref name="radio"> Germinoma. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016</ref>
MRI of the brain and spine with and without gadolinium is the imaging modality of choice for germinoma. On MRI, intracranial GCTs appear isointense or hypointense on T1 sequences and hyperintense on T2 sequences.<ref name="radio"> Germinoma. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016</ref>
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On ultrasound, germinoma is characterized by heterogeneous echogenic mass with cystic and solid components.
On ultrasound, germinoma is characterized by heterogeneous echogenic mass with cystic and solid components.
===Other Imaging Findings===
===Other Imaging Findings===
Other diagnostic studies for germinoma include PET scan.<ref name="pmid24272066">{{cite journal| author=Okochi Y, Nihashi T, Fujii M, Kato K, Okada Y, Ando Y et al.| title=Clinical use of (11)C-methionine and (18)F-FDG-PET for germinoma in central nervous system. | journal=Ann Nucl Med | year= 2014 | volume= 28 | issue= 2 | pages= 94-102 | pmid=24272066 | doi=10.1007/s12149-013-0787-4 | pmc=PMC3926980 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24272066  }} </ref>
Other diagnostic studies for germinoma include [[PET scan]].<ref name="pmid24272066">{{cite journal| author=Okochi Y, Nihashi T, Fujii M, Kato K, Okada Y, Ando Y et al.| title=Clinical use of (11)C-methionine and (18)F-FDG-PET for germinoma in central nervous system. | journal=Ann Nucl Med | year= 2014 | volume= 28 | issue= 2 | pages= 94-102 | pmid=24272066 | doi=10.1007/s12149-013-0787-4 | pmc=PMC3926980 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24272066  }} </ref>
===Other Diagnostic Studies===
===Other Diagnostic Studies===
Biopsy may be helpful in the diagnosis of germinoma. Findings on biopsy diagnostic of germinoma include undifferentiated, uniform large cells with abundant glycogen-rich cytoplasm arranged in nests separated by bands of connective tissue along trophoblastic lines.<ref name="pmid19329866">{{cite journal| author=Shibamoto Y| title=Management of central nervous system germinoma: proposal for a modern strategy. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 119-29 | pmid=19329866 | doi=10.1159/000210058 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329866  }} </ref>
Biopsy may be helpful in the diagnosis of germinoma. Findings on biopsy diagnostic of germinoma include undifferentiated, uniform large cells with abundant glycogen-rich cytoplasm arranged in nests separated by bands of connective tissue along trophoblastic lines.<ref name="pmid19329866">{{cite journal| author=Shibamoto Y| title=Management of central nervous system germinoma: proposal for a modern strategy. | journal=Prog Neurol Surg | year= 2009 | volume= 23 | issue=  | pages= 119-29 | pmid=19329866 | doi=10.1159/000210058 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19329866  }} </ref>
==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
The predominant therapy for CNS germ cell tumors is radiation therapy. Adjunctive chemotherapy and surgery may be required.<ref name="pmid14990640">{{cite journal| author=Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L et al.| title=Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. | journal=J Clin Oncol | year= 2004 | volume= 22 | issue= 5 | pages= 846-53 | pmid=14990640 | doi=10.1200/JCO.2004.07.006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14990640  }} </ref><ref name="pmid12872359">{{cite journal| author=Ogawa K, Toita T, Nakamura K, Uno T, Onishi H, Itami J et al.| title=Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients. | journal=Cancer | year= 2003 | volume= 98 | issue= 2 | pages= 369-76 | pmid=12872359 | doi=10.1002/cncr.11495 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12872359  }} </ref><ref name="pmid15102352">{{cite journal| author=Balmaceda C, Finlay J| title=Current advances in the diagnosis and management of intracranial germ cell tumors. | journal=Curr Neurol Neurosci Rep | year= 2004 | volume= 4 | issue= 3 | pages= 253-62 | pmid=15102352 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15102352  }} </ref><ref name="pmid15143087">{{cite journal| author=Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC et al.| title=Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. | journal=J Clin Oncol | year= 2004 | volume= 22 | issue= 10 | pages= 1934-43 | pmid=15143087 | doi=10.1200/JCO.2004.11.053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15143087  }} </ref>
The predominant therapy for CNS germ cell tumors is [[radiation therapy]]. Adjunctive [[chemotherapy]] and [[surgery]] may be required.<ref name="pmid14990640">{{cite journal| author=Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L et al.| title=Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. | journal=J Clin Oncol | year= 2004 | volume= 22 | issue= 5 | pages= 846-53 | pmid=14990640 | doi=10.1200/JCO.2004.07.006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14990640  }} </ref><ref name="pmid12872359">{{cite journal| author=Ogawa K, Toita T, Nakamura K, Uno T, Onishi H, Itami J et al.| title=Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients. | journal=Cancer | year= 2003 | volume= 98 | issue= 2 | pages= 369-76 | pmid=12872359 | doi=10.1002/cncr.11495 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12872359  }} </ref><ref name="pmid15102352">{{cite journal| author=Balmaceda C, Finlay J| title=Current advances in the diagnosis and management of intracranial germ cell tumors. | journal=Curr Neurol Neurosci Rep | year= 2004 | volume= 4 | issue= 3 | pages= 253-62 | pmid=15102352 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15102352  }} </ref><ref name="pmid15143087">{{cite journal| author=Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC et al.| title=Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. | journal=J Clin Oncol | year= 2004 | volume= 22 | issue= 10 | pages= 1934-43 | pmid=15143087 | doi=10.1200/JCO.2004.11.053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15143087  }} </ref>


===Surgery===
===Surgery===
Line 62: Line 65:


===Primary Prevention===
===Primary Prevention===
There are no primary preventive measures available for germinoma.
===Secondary Prevention===
===Secondary Prevention===
Secondary prevention strategies following germinoma include retreatment with the original regimen. For patients who received radiotherapy RT to a reduced volume, craniospinal irradiation CSI is considered the standard of care. Myeloablative high-dose chemotherapy with autologous stem cell rescue followed by additional RT can be considered, for patients who have already received craniospinal irradiation CSI.<ref name="pmid23824533">{{cite journal| author=Baek HJ, Park HJ, Sung KW, Lee SH, Han JW, Koh KN et al.| title=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. | journal=J Neurooncol | year= 2013 | volume= 114 | issue= 3 | pages= 329-38 | pmid=23824533 | doi=10.1007/s11060-013-1188-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23824533  }} </ref>
==References==
==References==
{{reflist|2}}
{{reflist|2}}
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Latest revision as of 23:35, 26 November 2017

Germinoma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]

Overview

The term germinoma most often refers to a tumor in the brain that has a histology identical to two other tumors: dysgerminoma in the ovary and seminoma in the testis. It may be benign or malignant. Germ cell tumors (GCTs) are classified as extragonadal if there is no evidence of a primary tumor in either the ovaries or the testes. Extragonadal GCTs typically arise in midline locations, and specific sites vary with age of the patient. In infants and young children, intracranial GCTs and sacrococcygeal teratomas are more common than other locations. In adults, the most common sites are the anterior retroperitoneum, mediastinum, and the pineal and suprasellar regions. Intracranial germ cell tumors are a heterogeneous group of lesions which occur in children and adults.[1] Germinoma may be classified according to World Health Organization into two groups: germinomas and nongerminomatous germ cell tumors. Based on the tumor markers secreted into the cerebrospinal fluid (CSF) and serum, as well as by the presence of histochemical markers on tumor cells, intracranial germ cell tumors may be classified into either secreting or non secreting tumors. Based on the prognosis of the tumor, intracranial germ cell tumors may be classified into either good, intermediate, or poor prognosis.[2][3][4] On gross pathology, smooth and bosselated external surface, and soft, fleshy and either cream-colored, gray, pink or tan interior are characteristic findings of germinoma. On microscopic histopathological analysis, uniform cells that resemble primordial germ cells, consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic are characteristic findings of germinoma. Genes involved in the pathogenesis of germinoma include gains of 1p, 8p, and 12q and losses of 13q and 18q, duplication of the short arm of chromosome 12, loss of 1p and 6q, alterations in sex chromosomes in children, alterations of the p14 gene, mutations of the c-kit gene, aberrations of CCND2 (12P13), and RB1, and gain-of-function mutations of KIT. The progression to germinoma usually involves the mutations of the KIT/RAS signalling or AKT1/mtor pathways and cyclin/CDK-RB-E2F pathway if CCND2 (12P13) and RB1 genes are aberrated.[5][6][7][8][9][10][11][12] The peak of germinoma occurs at ages 15-19 years: the median age at diagnosis is 10-12 years. CNS germ cell tumors commonly affects individuals between birth and 34 years of age. Males are more commonly affected with pineal germinoma than females. The male to female ratio is approximately 5-22 to 1. Females are more commonly affected with suprasellar germinoma than males. The female to male ratio is approximately 1.3:1. Symptoms of germinoma include headache, vomiting, papilledema, lethargy, somnolence, ataxia, behavioral changes, decline in academic performance, paralysis of upward gaze, paralysis of convergence, diabetes insipidus, delayed pubertal development, precocious puberty, isolated growth hormone deficiency, hypopituitarism (central hypothyroidism, adrenal insufficiency), decreased visual acuity from chiasmal or optic nerve compression, and visual field deficit (e.g, bitemporal hemianopsia). Presenting symptoms of patients with intracranial GCTs depend upon the location, size of the tumor, and the patient's age.[13][14][15] MRI of the brain and spine with and without gadolinium is the imaging modality of choice for germinoma. On MRI, intracranial GCTs appear isointense or hypointense on T1 sequences and hyperintense on T2 sequences.[16] The predominant therapy for CNS germ cell tumors is radiation therapy. Adjunctive chemotherapy and surgery may be required.[17][18][19][20] The feasibility of surgery depends on the type of the intracranial germ cell tumor at diagnosis. Surgery is not the first-line treatment option for patients with germ cell tumors. Surgery is usually reserved for patients with either NGGCTs, or in patients who have had an incomplete response to initial chemotherapy, and in patients with "growing teratoma syndrome".[21][22][13][23][24][25][26][27][17][28][29][30]

Historical Perspective

Classification

Germinoma may be classified according to World Health Organization into two groups: germinomas and nongerminomatous germ cell tumors. Based on the tumor markers secreted into the cerebrospinal fluid (CSF) and serum, as well as by the presence of histochemical markers on tumor cells, intracranial germ cell tumors may be classified into either secreting or non secreting tumors. Based on the prognosis of the tumor, intracranial germ cell tumors may be classified into either good, intermediate, or poor prognosis.[2][3][4]

Pathophysiology

On microscopic histopathological analysis, uniform cells that resemble primordial germ cells, consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic are characteristic findings of germinoma. Genes involved in the pathogenesis of germinoma include gains of 1p, 8p, and 12q and losses of 13q and 18q, duplication of the short arm of chromosome 12, loss of 1p and 6q, alterations in sex chromosomes in children, alterations of the p14 gene, mutations of the c-kit gene, aberrations of CCND2 (12P13), and RB1, and gain-of-function mutations of KIT. The progression to germinoma usually involves the mutations of the KIT/RAS signalling or AKT1/mtor pathways and cyclin/CDK-RB-E2F pathway if CCND2 (12P13) and RB1 genes are aberrated.[5][6][7][8][9][10][11][12]

Causes

There are no established causes for germinoma. However, several theories have been postulated to define the cause of germ cell tumors. GCTs arise from primordial germ cells that migrate to the germinal ridges in the developing embryo. The process of migration appears to be under the control of complex molecular events. Alteration in any of these molecular pathways may give rise to GCTs. Rather than laterally to genital ridges, some primordial germ cells that have left the yolk sac endoderm migrate aberrantly cranially towards the diencephalic midline structures.[21][31][7][8][32][33][34] Biopsy may be helpful in the diagnosis of germinoma. Findings on biopsy diagnostic of germinoma include undifferentiated, uniform large cells with abundant glycogen-rich cytoplasm arranged in nests separated by bands of connective tissue along trophoblastic lines.[23]

Epidemiology and Demographics

The peak of germinoma occurs at ages 15-19 years: the median age at diagnosis is 10-12 years. CNS germ cell tumors commonly affects individuals between birth and 34 years of age. Males are more commonly affected with pineal germinoma than females. The male to female ratio is approximately 5-22 to 1. Females are more commonly affected with suprasellar germinoma than males. The female to male ratio is approximately 1.3:1.

Risk Factors

There are no established risk factors for germinoma.

Screening

According to the United States Preventive Services Task Force, screening for extramammary Paget's disease is not recommended among the general population.[35]

Differential Diagnosis

Germinoma must be differentiated from other lesions in the pineal and suprasellar region, such as glial tumors which include astrocytomas and gangliomas, granular cell tumor, hamartomas, xanthogranuloma, meningiomas, colloid cysts, craniopharyngioma, cysticercosis, metastatic cancer with unknown primary site, pineal tumors, and pituitary macroadenomas.[16]

Natural History, Complications, and Prognosis

If left untreated, more than 50% of patients may continue to suffer from endocrine abnormalities such as growth hormone deficiency, growth retardation, hypopituitarism, and hypothyroidism, and may require lifelong hormonal replacement therapy. Common complications of germinoma include secondary cancers such as acute myeloid leukemia and radiation-induced brain neoplasms. Prognosis is generally excellent for germinomas, and the 5-year survival rate of patients with germinoma is approximately 70-90%. However, prognosis in general depends on the histological diagnosis and staging of the extent of disease.

Diagnosis

Staging

There is no established system for the staging of germ cell tumors, and most investigators utilize the TM system employed for staging medulloblastomas. Predominantly because of their midline location, staging for the size of the tumor at the time of diagnosis or after surgery (T-stage evaluation), has not been routinely employed in germ cell tumors.

History and Symptoms

Symptoms of germinoma include headache, vomiting, papilledema, lethargy, somnolence, ataxia, behavioral changes, decline in academic performance, paralysis of upward gaze, paralysis of convergence, diabetes insipidus, delayed pubertal development, precocious puberty, isolated growth hormone deficiency, hypopituitarism (central hypothyroidism, adrenal insufficiency), decreased visual acuity from chiasmal or optic nerve compression, and visual field deficit (e.g, bitemporal hemianopsia). Presenting symptoms of patients with intracranial GCTs depend upon the location, size of the tumor, and the patient's age.[13][14][15]

Physical Examination

Common physical examination findings of germinoma include paralysis of upward gaze, pupils nonreactive to light perception and accommodation or pupils which react better to accommodation than light, nystagmus, failure of convergence, lid retraction, papilledema, ataxia, and neurologic examination may be abnormal depending on the location of the tumor.

Laboratory Findings

An elevated concentration of AFP and beta-hCG in the serum and CSF, and CSF cytology to detect malignant cells is diagnostic of intracranial germ cell tumors. In patients in whom endoscopic biopsy is not considered possible, detection of elevated tumor markers may be sufficient for diagnosis.

Chest X Ray

Chest x-rays may be performed to detect metastases of germinoma to the lungs.

CT

Head and neck CT scan may be diagnostic of germinoma. Findings on CT scan suggestive of germinoma include hyperdensity compared to adjacent brain, pituitary stalk enhancement and thickening, and presence of calcification in the pineal region in the pediatric population.[16]

MRI

MRI of the brain and spine with and without gadolinium is the imaging modality of choice for germinoma. On MRI, intracranial GCTs appear isointense or hypointense on T1 sequences and hyperintense on T2 sequences.[16]

Ultrasound

On ultrasound, germinoma is characterized by heterogeneous echogenic mass with cystic and solid components.

Other Imaging Findings

Other diagnostic studies for germinoma include PET scan.[36]

Other Diagnostic Studies

Biopsy may be helpful in the diagnosis of germinoma. Findings on biopsy diagnostic of germinoma include undifferentiated, uniform large cells with abundant glycogen-rich cytoplasm arranged in nests separated by bands of connective tissue along trophoblastic lines.[23]

Treatment

Medical Therapy

The predominant therapy for CNS germ cell tumors is radiation therapy. Adjunctive chemotherapy and surgery may be required.[17][18][19][20]

Surgery

The feasibility of surgery depends on the type of the intracranial germ cell tumor at diagnosis. Surgery is not the first-line treatment option for patients with germ cell tumors. Surgery is usually reserved for patients with either NGGCTs, or in patients who have had an incomplete response to initial chemotherapy, and in patients with "growing teratoma syndrome".[21][22][13][23][24][25][26][27][17][28][29][30]

Primary Prevention

There are no primary preventive measures available for germinoma.

Secondary Prevention

Secondary prevention strategies following germinoma include retreatment with the original regimen. For patients who received radiotherapy RT to a reduced volume, craniospinal irradiation CSI is considered the standard of care. Myeloablative high-dose chemotherapy with autologous stem cell rescue followed by additional RT can be considered, for patients who have already received craniospinal irradiation CSI.[37]

References

  1. ↑ Packer, Roger J., Bruce H. Cohen, and Kathleen Cooney. "Intracranial germ cell tumors." The Oncologist 5.4 (2000): 312-320.
  2. ↑ 2.0 2.1 Louis, David N.; Ohgaki, Hiroko; Wiestler, Otmar D.; Cavenee, Webster K.; Burger, Peter C.; Jouvet, Anne; Scheithauer, Bernd W.; Kleihues, Paul (2007). "The 2007 WHO Classification of Tumours of the Central Nervous System". Acta Neuropathologica. 114 (2): 97–109. doi:10.1007/s00401-007-0243-4. ISSN 0001-6322.
  3. ↑ 3.0 3.1 Jennings MT, Gelman R, Hochberg F (1985). "Intracranial germ-cell tumors: natural history and pathogenesis". J Neurosurg. 63 (2): 155–67. doi:10.3171/jns.1985.63.2.0155. PMID 2991485.
  4. ↑ 4.0 4.1 Hoffman HJ, Otsubo H, Hendrick EB, Humphreys RP, Drake JM, Becker LE; et al. (1991). "Intracranial germ-cell tumors in children". J Neurosurg. 74 (4): 545–51. doi:10.3171/jns.1991.74.4.0545. PMID 1848284.
  5. ↑ 5.0 5.1 Rickert CH, Simon R, Bergmann M, Dockhorn-Dworniczak B, Paulus W (2000). "Comparative genomic hybridization in pineal germ cell tumors". J Neuropathol Exp Neurol. 59 (9): 815–21. PMID 11005262.
  6. ↑ 6.0 6.1 Schneider DT, Zahn S, Sievers S, Alemazkour K, Reifenberger G, Wiestler OD; et al. (2006). "Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization". Mod Pathol. 19 (6): 864–73. doi:10.1038/modpathol.3800607. PMID 16607373.
  7. ↑ 7.0 7.1 7.2 Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP; et al. (2007). "Malignant germ cell tumours of childhood: new associations of genomic imbalance". Br J Cancer. 96 (4): 667–76. doi:10.1038/sj.bjc.6603602. PMC 2360055. PMID 17285132.
  8. ↑ 8.0 8.1 8.2 Sato K, Takeuchi H, Kubota T (2009). "Pathology of intracranial germ cell tumors". Prog Neurol Surg. 23: 59–75. doi:10.1159/000210053. PMID 19329861.
  9. ↑ 9.0 9.1 Kamakura Y, Hasegawa M, Minamoto T, Yamashita J, Fujisawa H (2006). "C-kit gene mutation: common and widely distributed in intracranial germinomas". J Neurosurg. 104 (3 Suppl): 173–80. doi:10.3171/ped.2006.104.3.173. PMID 16572634.
  10. ↑ 10.0 10.1 Sakuma Y, Sakurai S, Oguni S, Satoh M, Hironaka M, Saito K (2004). "c-kit gene mutations in intracranial germinomas". Cancer Sci. 95 (9): 716–20. PMID 15471556.
  11. ↑ 11.0 11.1 Wang HW, Wu YH, Hsieh JY, Liang ML, Chao ME, Liu DJ; et al. (2010). "Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations". BMC Genomics. 11: 132. doi:10.1186/1471-2164-11-132. PMC 2837036. PMID 20178649.
  12. ↑ 12.0 12.1 Terashima K, Yu A, Chow WY, Hsu WC, Chen P, Wong S; et al. (2014). "Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors". Pediatr Blood Cancer. 61 (4): 593–600. doi:10.1002/pbc.24833. PMID 24249158.
  13. ↑ 13.0 13.1 13.2 13.3 Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM (2013). "Delayed diagnosis in children with intracranial germ cell tumors". J Pediatr. 163 (5): 1448–53. doi:10.1016/j.jpeds.2013.06.024. PMID 23896184.
  14. ↑ 14.0 14.1 Packer RJ, Cohen BH, Cooney K, Coney K (2000). "Intracranial germ cell tumors". Oncologist. 5 (4): 312–20. PMID 10964999.
  15. ↑ 15.0 15.1 Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, LaFond DA; et al. (2007). "CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis". Neurology. 68 (20): 1668–73. doi:10.1212/01.wnl.0000261908.36803.ac. PMID 17502547.
  16. ↑ 16.0 16.1 16.2 16.3 Germinoma. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016
  17. ↑ 17.0 17.1 17.2 17.3 Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L; et al. (2004). "Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol". J Clin Oncol. 22 (5): 846–53. doi:10.1200/JCO.2004.07.006. PMID 14990640.
  18. ↑ 18.0 18.1 Ogawa K, Toita T, Nakamura K, Uno T, Onishi H, Itami J; et al. (2003). "Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients". Cancer. 98 (2): 369–76. doi:10.1002/cncr.11495. PMID 12872359.
  19. ↑ 19.0 19.1 Balmaceda C, Finlay J (2004). "Current advances in the diagnosis and management of intracranial germ cell tumors". Curr Neurol Neurosci Rep. 4 (3): 253–62. PMID 15102352.
  20. ↑ 20.0 20.1 Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC; et al. (2004). "Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors". J Clin Oncol. 22 (10): 1934–43. doi:10.1200/JCO.2004.11.053. PMID 15143087.
  21. ↑ 21.0 21.1 21.2 Echevarría ME, Fangusaro J, Goldman S (2008). "Pediatric central nervous system germ cell tumors: a review". Oncologist. 13 (6): 690–9. doi:10.1634/theoncologist.2008-0037. PMID 18586924.
  22. ↑ 22.0 22.1 Kaur H, Singh D, Peereboom DM (2003). "Primary central nervous system germ cell tumors". Curr Treat Options Oncol. 4 (6): 491–8. PMID 14585229.
  23. ↑ 23.0 23.1 23.2 23.3 Shibamoto Y (2009). "Management of central nervous system germinoma: proposal for a modern strategy". Prog Neurol Surg. 23: 119–29. doi:10.1159/000210058. PMID 19329866.
  24. ↑ 24.0 24.1 Sawamura Y (2009). "Strategy of combined treatment of germ cell tumors". Prog Neurol Surg. 23: 86–95. doi:10.1159/000210055. PMID 19329863.
  25. ↑ 25.0 25.1 Kretschmar C, Kleinberg L, Greenberg M, Burger P, Holmes E, Wharam M (2007). "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. 48 (3): 285–91. doi:10.1002/pbc.20815. PMC 4086720. PMID 16598761.
  26. ↑ 26.0 26.1 Finlay J, da Silva NS, Lavey R, Bouffet E, Kellie SJ, Shaw E; et al. (2008). "The management of patients with primary central nervous system (CNS) germinoma: current controversies requiring resolution". Pediatr Blood Cancer. 51 (2): 313–6. doi:10.1002/pbc.21555. PMID 18421722.
  27. ↑ 27.0 27.1 Janmohamed S, Grossman AB, Metcalfe K, Lowe DG, Wood DF, Chew SL; et al. (2002). "Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen". Clin Endocrinol (Oxf). 57 (4): 487–500. PMID 12354131.
  28. ↑ 28.0 28.1 Saran, Frank; Peoples, Sharon (2008). "Pineal Tumors: Germinomas and Non-Germinomatous Germ Cell Tumors": 310–317. doi:10.1002/9781444300222.ch41.
  29. ↑ 29.0 29.1 Peltier J, Vinchon M, Baroncini M, Kerdraon O, Dhellemmes P (2008). "Bifocal mixed germ-cell tumor with growing teratoma syndrome and metachronous mature metastases: case report". J Neurooncol. 90 (1): 111–5. doi:10.1007/s11060-008-9640-3. PMID 18574668.
  30. ↑ 30.0 30.1 Friedman JA, Lynch JJ, Buckner JC, Scheithauer BW, Raffel C (2001). "Management of malignant pineal germ cell tumors with residual mature teratoma". Neurosurgery. 48 (3): 518–22, discussion 522-3. PMID 11270541.
  31. ↑ Jubran RF, Finlay J (2005). "Central nervous system germ cell tumors: controversies in diagnosis and treatment". Oncology (Williston Park). 19 (6): 705–11, discussion 711-2, 715–7, 721. PMID 15971448.
  32. ↑ Pereda J, Motta PM (1991). "A unique fibrillar coat on the surface of migrating human primordial germ cells". Arch Histol Cytol. 54 (4): 419–25. PMID 1760220.
  33. ↑ Godin I, Wylie CC (1991). "TGF beta 1 inhibits proliferation and has a chemotropic effect on mouse primordial germ cells in culture". Development. 113 (4): 1451–7. PMID 1811953.
  34. ↑ Horowitz MB, Hall WA (1991). "Central nervous system germinomas. A review". Arch Neurol. 48 (6): 652–7. PMID 2039390.
  35. ↑ http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=germinoma Accessed on January 26, 2016.
  36. ↑ Okochi Y, Nihashi T, Fujii M, Kato K, Okada Y, Ando Y; et al. (2014). "Clinical use of (11)C-methionine and (18)F-FDG-PET for germinoma in central nervous system". Ann Nucl Med. 28 (2): 94–102. doi:10.1007/s12149-013-0787-4. PMC 3926980. PMID 24272066.
  37. ↑ Baek HJ, Park HJ, Sung KW, Lee SH, Han JW, Koh KN; et al. (2013). "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. 114 (3): 329–38. doi:10.1007/s11060-013-1188-1. PMID 23824533.


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