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Germinoma

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

Synonyms and keywords: Intracranial germ cell tumor; germ cell tumor; GCTs; NGGCTs; Nongerminomatous germ cell tumor; CNS germinoma; germ cell neoplasm

Overview

Overview

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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Historical Perspective

Historical Perspective

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References


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Classification

Classification

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

Overview

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.[1][2][3]

Classification

  • Based on the histology, germinoma may be classified according to World Health Organization into two groups:[1][2][3]
  • Germinomas
  • Nongerminomatous germ cell tumors
  • Tumors that consists of more than one of the above histological types are termed mixed GCTs
  • Pure germinomas account for 65% of all CNS germ cell tumors GCTs
  • Germinomas with mature and/or immature teratoma account for 15% of all CNS germ cell tumors
  • Mixed germinomas and nongerminomatous germ cell tumors NGGCTs represent approximately 20% of CNS germ cell tumors.[4]
  • Classification of germinoma according to World Health Organization is shown below in a tabular form:
CNS germ cell tumor
Germinoma
Pure with syncytiotrophoblasts
Nongerminomatous germ cell tumors
Teratoma- Mature and malignant
Embryonal carcinoma
Yolk sac tumor/endodermal sinus tumor
Choriocarcinoma


  • 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.
  • Secreted tumor markers measured in the CSF and serum include beta-human chorionic gonadotropin (beta-hCG) and alpha-fetoprotein (AFP), and immunohistochemistry is used to detect placental alkaline phosphatase (PLAP) and c-Kit on tumor cells. Secreting tumors are commonly defined as germ cell tumors with CSF beta-hCG level >50 international unit/L and/or a CSF AFP >10 microg/L.
  • Pure germinomas generally are associated with absent beta-hCG and AFP levels in both serum and CSF. Although an elevated AFP in either the CSF and serun rules out a pure germinoma, a minority of germinomas are associated with elevated beta-hCG levels in the serum and/or CSF.[5]
Tumor type Marker
b-HCG AFP PLAP c-kit
Pure germinoma – – +/- +
Germinoma(syncytiotrophoblastic) + – +/- +
Endodermal sinus tumor – + +/- –
Choriocarcinoma + – +/- –
Embryonal carcinoma – – + –
Mixed GCT +/- +/- +/- +/-
Mature teratoma – – – –
Immature teratoma +/- +/- – +/-


References

  1. ↑ 1.0 1.1 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.
  2. ↑ 2.0 2.1 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.
  3. ↑ 3.0 3.1 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.
  4. ↑ Villano JL, Propp JM, Porter KR, Stewart AK, Valyi-Nagy T, Li X; et al. (2008). “Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries”. Neuro Oncol. 10 (2): 121–30. doi:10.1215/15228517-2007-054. PMC 2613814. PMID 18287340.
  5. ↑ Ogino H, Shibamoto Y, Takanaka T, Suzuki K, Ishihara S, Yamada T; et al. (2005). “CNS germinoma with elevated serum human chorionic gonadotropin level: clinical characteristics and treatment outcome”. Int J Radiat Oncol Biol Phys. 62 (3): 803–8. doi:10.1016/j.ijrobp.2004.10.026. PMID 15936563.


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Pathophysiology

Pathophysiology

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

Overview

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.[1][2][3][4][5][6][7][8]

Pathophysiology

Pineal lesions occur more commonly than suprasellar lesions, at a ratio of 2:1. The location of the tumor that compromises total percentage of central nervous system (CNS) germ cell tumors is shown below in a tabular form:[9]

Location of the tumor % of CNS GCT
Pineal area
  • 50-60% of CNS germ cell tumors
Suprasellar area
  • 30-40%
Basal ganglia, thalamus, cerebral hemisphere
  • 5-10%
Both pineal and suprasellar region
  • 6-13%

The relationship of the gender with location of the CNS germ cell tumors is shown below in a tabular form:[10]

Sex Location of the tumor
Males
  • 70% of the tumors occur in the pineal area
Females
  • 75% of the CNS germ cell tumors occur in the suprasellar area

Gross Pathology

On gross examination, the external surface is smooth and bosselated (knobby), and the interior is soft, fleshy and either cream, gray, pink, or tan colored.[11]

Microscopic Pathology

Microscopic examination typically reveals uniform cells that resemble primordial germ cells. Typically, the stroma contains lymphocytes and about 20% of patients have sarcoid-like granulomas. The tumor is uniform in appearance, consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic. Pure germinomas are composed of large polygonal undifferentiated cells with abundant cytoplasm arranged in nests separated by bands of connective tissue. The histologic appearance of nongerminomatous germ cell tumors (NGGCTs) varies depending upon the specific cell types present.[11]

Pathogenesis

  • Central nervous cell germ cell tumors (GCTs) are believed to arise from nests of embryonic cells arrested during their migration in fetal development in the midline structures. As a result, central nervous system germ cell tumors are found in midline sites, especially in the suprasellar and pineal gland regions.
  • The germ cell theory has postulated that these tumors arise from primordial germ cells that have migrated aberrantly during embryonic development and subsequently undergone malignant transformation. However, the embryonic cell theory suggests that GCTs arise from a mis migrational pluripotent embryonic cell. It is postulated that pure germinomas arise from germ cells whereas mixed non germinomatous germ cell tumors NGGCTs are a result of misfolding and misplacement of embryonic cells into the lateral mesoderm, causing these cells to become entrapped in different areas of the brain.[12][13]
  • Intracranial GCTs express germ cell–specific proteins comprising NY-ESO-1, MAGE-A4, and TSPY, which are associated with embryonic stem cell pluripotency, which indicate that germ cell tumors (GCTs) may originate from primordial germ cells.[14][15][16][17]

Genetics

  • In adult-onset extragonadal germinomas, the most common abnormality is duplication of the short arm of chromosome 12.[18]
  • Cytogenetic abnormalities in children include loss of 1p and 6q, alterations in sex chromosomes, and abnormalities in 12p. In a study involving children, a subset of patients with pineal tumors demonstrated a gain of chromosomal material at 12p.[19]
  • In majority of cases, the most common chromosomal imbalance comprises gains of 1p, 8p, and 12q and losses of 13q and 18q.
  • The most frequent genotype abnormality is XXY, similar to that in Klinefelter syndrome. Individuals with Klinefelter syndrome are prone to develop intracranial GCTs, as are those with neurofibromatosis type 1 and Down syndrome.[20][21]
  • Gene p14 plays an important role in the development of intracranial germ cell tumors as frequent alterations of the p14 gene have been detected, especially in intracranial pure germinomas.[4]
  • In approximately 23-25% of intracranial germinomas, mutations of the c-kit gene have been found. Amplification of c-myc and n-myc have been known to be implicated in the development of intracranial germinomas.[22][6]
  • Frequent aberrations of CCND2 (12P13), and RB1 has indicated that there might be possibility of cyclin/CDK-RB-E2F pathway involvement in the pathogenesis of intracranial germ cell tumors. Gains in the transcriptional regulator PRDM14 have also been implicated in the pathogenesis of germ cell tumors. A recent study of 62 patients with intracranial GCT has shown that more than 50% had mutations of the KIT/RAS signalling or AKT1/mtor pathways.[1][2][3][4][5][6][7][8][23][5][6]

References

  1. ↑ 1.0 1.1 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.
  2. ↑ 2.0 2.1 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.
  3. ↑ 3.0 3.1 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.
  4. ↑ 4.0 4.1 4.2 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.
  5. ↑ 5.0 5.1 5.2 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.
  6. ↑ 6.0 6.1 6.2 6.3 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.
  7. ↑ 7.0 7.1 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.
  8. ↑ 8.0 8.1 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.
  9. ↑ Germ cell tumors. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016
  10. ↑ Villano JL, Propp JM, Porter KR, Stewart AK, Valyi-Nagy T, Li X; et al. (2008). “Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries”. Neuro Oncol. 10 (2): 121–30. doi:10.1215/15228517-2007-054. PMC 2613814. PMID 18287340.
  11. ↑ 11.0 11.1 germinoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Germinoma Accessed on January 26, 2016
  12. ↑ Sano K (1995). “So-called intracranial germ cell tumours: are they really of germ cell origin?”. Br J Neurosurg. 9 (3): 391–401. PMID 7546360.
  13. ↑ “Pathogenesis of intracranial germ cell tumors reconsidered in: Journal of Neurosurgery Volume 90 Issue 2 (1999)”.
  14. ↑ Packer RJ, Cohen BH, Cooney K, Coney K (2000). “Intracranial germ cell tumors”. Oncologist. 5 (4): 312–20. PMID 10964999.
  15. ↑ Teilum, Gunnar. Special tumors of ovary and testis and related extragonadal lesions : comparative pathology and histological identification. Copenhagen Philadelphia: Munksgaard J.B. Lippincott, 1976. Print.
  16. ↑ Nomura K (2001). “Epidemiology of germ cell tumors in Asia of pineal region tumor”. J Neurooncol. 54 (3): 211–7. PMID 11767288.
  17. ↑ Sano K, Matsutani M, Seto T (1989). “So-called intracranial germ cell tumours: personal experiences and a theory of their pathogenesis”. Neurol Res. 11 (2): 118–26. PMID 2569683.
  18. ↑ Bussey KJ, Lawce HJ, Himoe E, Shu XO, Suijkerbuijk RF, Olson SB, Magenis RE (March 2001). “Chromosomes 1 and 12 abnormalities in pediatric germ cell tumors by interphase fluorescence in situ hybridization”. Cancer Genet. Cytogenet. 125 (2): 112–8. PMID 11369053.
  19. ↑ Gömöri E, Halbauer DJ, Dóczi T, Balázs E, Kajtár P, Pajor L (December 2000). “Cytogenetic profile of primary pituitary germinoma”. J. Neurooncol. 50 (3): 251–5. PMID 11263505.
  20. ↑ Arens R, Marcus D, Engelberg S, Findler G, Goodman RM, Passwell JH (March 1988). “Cerebral germinomas and Klinefelter syndrome. A review”. Cancer. 61 (6): 1228–31. PMID 3277702.
  21. ↑ Ellis SJ, Crockard A, Barnard RO (February 1986). “Klinefelter’s syndrome, cerebral germinoma, Chiari malformation, and syrinx: a case report”. Neurosurgery. 18 (2): 220–2. PMID 2421193.
  22. ↑ Estiar MA, Fazilaty H, Aslanabadi S, Seifi M, Varghaei P, Rezamand A (September 2014). “MYCN gene amplification in patients with neuroblastic tumors”. Cell. Mol. Biol. (Noisy-le-grand). 60 (3): 23–8. PMID 25231001.
  23. ↑ Wang L, Yamaguchi S, Burstein MD, Terashima K, Chang K, Ng HK; et al. (2014). “Novel somatic and germline mutations in intracranial germ cell tumours”. Nature. 511 (7508): 241–5. doi:10.1038/nature13296. PMC 4532372. PMID 24896186.


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Causes

Causes

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

Overview

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.[1][2][3][4][5][6][7]

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.[1][2][3][4][5][6][7]

Important factors in cell migration include the following:

  • Extracellular matrix
  • Chemotropic factors
  • Tumor growth factor beta 1

Since the maturation of the fetal hypothalamus coincides with the migration of primordial germ cells, the fetal hypothalamus may secrete chemotrophic factors that attract primordial germ cells to the diencephalon.

References

  1. ↑ 1.0 1.1 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.
  2. ↑ 2.0 2.1 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.
  3. ↑ 3.0 3.1 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.
  4. ↑ 4.0 4.1 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.
  5. ↑ 5.0 5.1 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.
  6. ↑ 6.0 6.1 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.
  7. ↑ 7.0 7.1 Horowitz MB, Hall WA (1991). “Central nervous system germinomas. A review”. Arch Neurol. 48 (6): 652–7. PMID 2039390.


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Epidemiology and Demographics

Epidemiology and Demographics

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

Overview

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.

Epidemiology and Demographics

  • Germinomas account for approximately 5% of all intracranial tumors seen in individuals younger than 20 years of age.
  • Pineal lesions occur more commonly than suprasellar lesions, at a ratio of 2:1. Tumors of the pineal area comprise 50-60% of CNS germ cell tumors; those of the suprasellar region comprise 30-40%. CNS germ cell tumors may also occur in the thalamus, basal ganglia, and cerebral hemispheres.
  • Primary CNS germ cell tumors are more common in Japan and other countries in Asia compared with North America.
  • Primary CNS germ cell tumors account for approximately 2-3% of all intracranial tumors and approximately 8-15% of pediatric brain tumors in the Far East.
  • Location of CNS germ cell tumors also varies by sex. In males, approximately 70% of tumors occur in the pineal area; In females, approximately 75% of CNS germ cell tumors occur in the suprasellar areas.
  • Approximately 90% of patients with germ cell tumors are younger than 20 at the time of diagnosis.[1][2][3][4][5][6]

Incidence

The incidence of germinoma is approximately 0.2 per 100,000 individuals worldwide.[7][1][8]

Age

The peak incidence 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. Germinomas are considered primarily a disease of adolescents and young adults.

Age distribution of CNS germ cell tumors is shown below in a tabular from:[9]

Age percentage % of cases of germ cell tumors
0-14 years
  • 34%
15-29 years
  • 57%
30-44 years
  • 9%

Race

Germinoma usually affects individuals of the Asian race. Caucasian individuals are less likely to develop germinoma.[2][10]

Gender

Gender ratios are different depending on location. In the pineal region there is a marked male preponderance with a male to female ratio of 5-22:1 whereas in the suprasellar region, there is slight female preponderance with a male to female ratio of 1:1.3. Due to the pineal region being most common, germinomas are seen more frequently in males. An overall male predominance is noted in CNS germ cell tumors. The incidence of CNS germ cell tumors in males, all ages combined, was 3.7 times that seen in females.[6][11]

References

  1. ↑ 1.0 1.1 Keene D, Johnston D, Strother D, Fryer C, Carret AS, Crooks B; et al. (2007). “Epidemiological survey of central nervous system germ cell tumors in Canadian children”. J Neurooncol. 82 (3): 289–95. doi:10.1007/s11060-006-9282-2. PMID 17120159.
  2. ↑ 2.0 2.1 Matsutani M, Japanese Pediatric Brain Tumor Study Group (2001). “Combined chemotherapy and radiation therapy for CNS germ cell tumors–the Japanese experience”. J Neurooncol. 54 (3): 311–6. PMID 11767296.
  3. ↑ Saran, Frank; Peoples, Sharon (2008). “Pineal Tumors: Germinomas and Non-Germinomatous Germ Cell Tumors”: 310–317. doi:10.1002/9781444300222.ch41.
  4. ↑ McCarthy BJ, Shibui S, Kayama T, Miyaoka E, Narita Y, Murakami M; et al. (2012). “Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries”. Neuro Oncol. 14 (9): 1194–200. doi:10.1093/neuonc/nos155. PMC 3424216. PMID 22869621.
  5. ↑ 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.
  6. ↑ 6.0 6.1 Goodwin TL, Sainani K, Fisher PG (2009). “Incidence patterns of central nervous system germ cell tumors: a SEER Study”. J Pediatr Hematol Oncol. 31 (8): 541–4. doi:10.1097/MPH.0b013e3181983af5. PMID 19636276.
  7. ↑ Villano JL, Propp JM, Porter KR, Stewart AK, Valyi-Nagy T, Li X; et al. (2008). “Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries”. Neuro Oncol. 10 (2): 121–30. doi:10.1215/15228517-2007-054. PMC 2613814. PMID 18287340.
  8. ↑ 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.
  9. ↑ Kaur H, Singh D, Peereboom DM (2003). “Primary central nervous system germ cell tumors”. Curr Treat Options Oncol. 4 (6): 491–8. PMID 14585229.
  10. ↑ Matsutani M (2009). “Pineal germ cell tumors”. Prog Neurol Surg. 23: 76–85. doi:10.1159/000210054. PMID 19329862.
  11. ↑ Germ cell tumors. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016


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Risk Factors

Risk Factors

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

Overview

There are no established risk factors for germinoma.

Risk Factors

There are no established risk factors for germinoma.

References


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Screening

Screening

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

Overview

According to the United States Preventive Services Task Force, screening for germinoma is not recommended among the general population.

Screening

According to the United States Preventive Services Task Force, screening for germinoma is not recommended among the general population.[1]

References

  1. ↑ http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=germinoma Accessed on January 26, 2016.


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Differentiating Germinoma from other Diseases

Differentiating Germinoma from other Diseases

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

Overview

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.[1]

Differential Diagnosis

Differential diagnosis of germinoma includes the following:[1]

References

  1. ↑ 1.0 1.1 Germ cell tumors. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016


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Natural History, Complications and Prognosis

Natural History, Complications and Prognosis

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

Overview

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.

Natural History

  • Usually, patients with tumors in the pineal region tend to present with a brief history of symptoms compared with tumors of the basal ganglionic or suprasellar region, which presents a long history of symptoms including double vision related to tectal and aqueductal compression.[1]
  • Approximately 35% of patients with suprasellar tumors will be asymptomatic for more than six months, and in these patients, the time between first symptom and diagnosis may be prolonged. Tumors arising in the suprasellar region often present with overt or subtle hormonal deficiencies and a prolonged prodrome often lasting months to years. A wide majority of patients may present with diabetes insipidus as the presenting finding; patients can usually compensate for antidiuretic hormone deficiency for months to years by drinking excessive amounts of fluid. This consequently leads to development of hormonal and visual changes as the tumor expands dorsally and compresses the optic chiasm. Symptoms related to endocrinopathy (delayed vertical growth, diabetes insipidus, etc.) are associated with delays in diagnosis of greater than 12 months, and are associated with higher incidences of disseminated disease.[2][3]
  • In approximately 22% of cases metastasis has been noted at time of diagnosis.
  • The presentation is often delayed with the tumors of the thalami and basal ganglia, with a larger tumor at diagnosis.
  • Although germ cell tumors may be disseminated at the time of diagnosis, signs and symptoms of spinal cord or cerebral cortical involvement are uncommon, except for some infrequent cases of germinomas which arise in the basal ganglionic region or thalamus.[4][5][6][7][8][9][10]

Complications

  • Patients with intracranial tumors located in the basal ganglia perform poorly compared with those who have tumors in the suprasellar and pineal regions; they have lower short-term retention of visual and verbal stimuli and full-scale IQs.
  • Larger irradiation volume and dose effect the following functions of the brain adversely:[11]
    • Intellectual functions
    • Concept
    • Executive function
    • Memory
    • Decline in neurocognitive function, and performance IQs
  • Approximately 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[12][13]
  • Due to surgical resection of tumor or due surgical biopsies the following complications may occur:
    • Poor performance in psychosocial skills
    • Behavioral dysfunction
    • Financial difficulties
    • Lower KPS scores following surgery have been associated with impaired neurocognitive function
  • Complications related to chemotherapy may develop
  • The surgical morbidity associated with pineal-region tumors is approximately 2-5%. Patients may suffer from the following:
    • Transient movement abnormalities of eyes
    • Ataxia
    • Cognitive dysfunction
  • The other complications that may present in patients with intracranial germ cell tumors are following:
  • The incidence of secondary cancer is approximately 6%, in patients with intracranial tumors. The risk of death due to malignancy is approximately 16%. Radiation therapy and chemotherapy may both promote the development of secondary cancers such as acute myeloid leukemia and radiation-induced brain neoplasms.[14][15][16][17][18][19][20][21]

Prognosis

The following two factors are of prognostic significance:

  • Histological diagnosis
    • Germinomas were associated with significantly longer survival than nongerminomatous GCT’s
  • Staging of the extent of disease
  • Generally, germinomas are associated with an excellent prognosis. Intracranial germinomas have a reported 90% survival to five years after diagnosis.[23] The 10-year survival of germinomas is 70%.

Based on the prognosis of the tumor, intracranial germ cell tumors may be classified into either good, intermediate, or poor prognosis. Pure germinomas carry a better prognosis than non germinomatous germ cell tumors (NGGCTs). Secreting germ cell tumors (GCTs) are generally considered to behave more aggressively and carry a poorer prognosis than nonsecreting germ cell tumors GCTs.[24][25]

Prognosis Type of intracranial germ cell tumors Survival %
Good prognosis
  • Pure germinomas
  • Mature teratomas
 90 %
Poor prognosis
 40 %
Intermediate prognosis
  • Germinoma with syncytiotrophoblastic giant cells
  • Immature teratoma
  • Mixed tumors mainly composed of germinoma or teratoma
  • Teratoma with malignant transformation
 70 %

The prognosis of various germ cell tumors is shown below in a tabular form:

Type of tumor 5-year survival rate
Germinoma
  • 70-90%
Mixed germ cell tumors
  • 60-80%
Nongerminomatous germ cell tumors
  • 30-50%

References

  1. ↑ “Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®) – PDQ Cancer Information Summaries – NCBI Bookshelf”.
  2. ↑ Kilday JP, Laughlin S, Urbach S, Bouffet E, Bartels U (January 2015). “Diabetes insipidus in pediatric germinomas of the suprasellar region: characteristic features and significance of the pituitary bright spot”. J. Neurooncol. 121 (1): 167–75. doi:10.1007/s11060-014-1619-7. PMID 25266413.
  3. ↑ Frappaz D, Pedone C, Thiesse P, Szathmari A, Conter CF, Mottolese C, Carrie C (October 2017). “Visual complaints in intracranial germinomas”. Pediatr Blood Cancer. 64 (10). doi:10.1002/pbc.26543. PMID 28436607.
  4. ↑ Germ cell tumors. National Cancer Institute(2015) http://www.cancer.gov/types/brain/hp/child-cns-germ-cell-treatment-pdq#link/_60_toc Accessed on February 16, 2016
  5. ↑ Afzal S, Wherrett D, Bartels U, Tabori U, Huang A, Stephens D; et al. (2010). “Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy”. J Neurooncol. 97 (3): 393–9. doi:10.1007/s11060-009-0033-z. PMID 19820898.
  6. ↑ 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.
  7. ↑ Packer, Roger J., Bruce H. Cohen, and Kathleen Cooney. “Intracranial germ cell tumors.” The Oncologist 5.4 (2000): 312-320.
  8. ↑ Germ cell tumors. Radiopedia(2015) http://radiopaedia.org/articles/central-nervous-system-germinoma Accessed on January 25, 2016
  9. ↑ Germinoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Germinoma Accessed on January 26, 2016
  10. ↑ 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.
  11. ↑ Giglio P, Gilbert MR (January 2010). “Neurologic complications of cancer and its treatment”. Curr Oncol Rep. 12 (1): 50–9. doi:10.1007/s11912-009-0071-x. PMC 3637950. PMID 20425608.
  12. ↑ Hale GA, Marina NM, Jones-Wallace D, Greenwald CA, Jenkins JJ, Rao BN, Luo X, Hudson MM (1999). “Late effects of treatment for germ cell tumors during childhood and adolescence”. J. Pediatr. Hematol. Oncol. 21 (2): 115–22. PMID 10206457.
  13. ↑ Barnes N, Chemaitilly W (2014). “Endocrinopathies in survivors of childhood neoplasia”. Front Pediatr. 2: 101. doi:10.3389/fped.2014.00101. PMC 4172013. PMID 25295241.
  14. ↑ Sugiyama K, Yamasaki F, Kurisu K, Kenjo M (2009). “Quality of life of extremely long-time germinoma survivors mainly treated with radiotherapy”. Prog Neurol Surg. 23: 130–9. doi:10.1159/000210059. PMID 19329867.
  15. ↑ Sutton LN, Radcliffe J, Goldwein JW, Phillips P, Janss AJ, Packer RJ; et al. (1999). “Quality of life of adult survivors of germinomas treated with craniospinal irradiation”. Neurosurgery. 45 (6): 1292–7, discussion 1297-8. PMID 10598695.
  16. ↑ Jinguji S, Yoshimura J, Nishiyama K, Aoki H, Nagasaki K, Natsumeda M; et al. (2013). “Factors affecting functional outcomes in long-term survivors of intracranial germinomas: a 20-year experience in a single institution”. J Neurosurg Pediatr. 11 (4): 454–63. doi:10.3171/2012.12.PEDS12336. PMID 23373627.
  17. ↑ Acharya S, DeWees T, Shinohara ET, Perkins SM (2015). “Long-term outcomes and late effects for childhood and young adulthood intracranial germinomas”. Neuro Oncol. 17 (5): 741–6. doi:10.1093/neuonc/nou311. PMC 4482856. PMID 25422317.
  18. ↑ Martens T, Rotermund R, Zu Eulenburg C, Westphal M, Flitsch J (2014). “Long-term follow-up and quality of life in patients with intracranial germinoma”. Neurosurg Rev. 37 (3): 445–50, discussion 451. doi:10.1007/s10143-014-0544-8. PMID 24715277.
  19. ↑ Odagiri K, Omura M, Hata M, Aida N, Niwa T, Ogino I; et al. (2012). “Treatment outcomes, growth height, and neuroendocrine functions in patients with intracranial germ cell tumors treated with chemoradiation therapy”. Int J Radiat Oncol Biol Phys. 84 (3): 632–8. doi:10.1016/j.ijrobp.2011.12.084. PMID 22420962.
  20. ↑ Ogawa K, Shikama N, Toita T, Nakamura K, Uno T, Onishi H; et al. (2004). “Long-term results of radiotherapy for intracranial germinoma: a multi-institutional retrospective review of 126 patients”. Int J Radiat Oncol Biol Phys. 58 (3): 705–13. doi:10.1016/j.ijrobp.2003.07.001. PMID 14967424.
  21. ↑ Liang SY, Yang TF, Chen YW, Liang ML, Chen HH, Chang KP; et al. (2013). “Neuropsychological functions and quality of life in survived patients with intracranial germ cell tumors after treatment”. Neuro Oncol. 15 (11): 1543–51. doi:10.1093/neuonc/not127. PMC 3813422. PMID 24101738.
  22. ↑ 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.
  23. ↑ Packer RJ, Cohen BH, Cooney K, Coney K (2000). “Intracranial germ cell tumors”. Oncologist. 5 (4): 312–20. PMID 10964999.
  24. ↑ Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N; et al. (1997). “Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases”. J Neurosurg. 86 (3): 446–55. doi:10.3171/jns.1997.86.3.0446. PMID 9046301.
  25. ↑ Matsutani M, Japanese Pediatric Brain Tumor Study Group (2001). “Combined chemotherapy and radiation therapy for CNS germ cell tumors–the Japanese experience”. J Neurooncol. 54 (3): 311–6. PMID 11767296.


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