Tumores de células germinales intracraneales: aspectos básicos, abordaje diagnóstico y alternativas terapéuticas
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oct 7, 2021
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Resumen
Introducción: Los Tumores de células germinales son neoplasias originadas por precursores de los gametos que, por defectos en procesos embriológicos migratorios, pueden aparecer en órganos extragonadales como el Encéfalo, donde constituyen un grupo variado y cada vez más frecuente de tumores. Objetivo: Exponer información relevante y actualizada sobre los procesos genéticos, fisiopatológicos y clínicos de los Tumores de células germinales intracraneales.
Materiales y métodos: Búsqueda sistematizada de publicaciones científicas, mediante la estrategia PICO, en bases de datos electrónicas. Conclusiones: Los tumores de células germinales intracraneales se clasifican en Germinoma y tumores de células germinales no germinomatosas. Dichos subgrupos representan una gran paradoja, ya que, pese a tener un origen común, son muy distintos entre sí. Los cambios genéticos que sustentan la génesis de ambos tumores son completamente opuestos: los Germinomas se caracterizan por presentar hipometilación del ADN y los no germinomas hipermetilación. Histológicamente, los tumores no germinomatosos muestran células menos diferenciadas con alta tasa mitótica, lo que les confiere mal pronóstico, contrario al Germinoma, que por sus características citológicas es menos agresivo. El diagnóstico supone la medición de Biomarcadores, que suelen ser negativos para el germinoma y positivos para los no germinomas; las neuroimágenes no ofrecen mayor información diferencial, y la confirmación es histológica. El tratamiento atiende al pronóstico, por ello será más impetuoso para los tumores no germinomatosos.
Keywords
Cáncer. Diagnóstico. Genes. Histología. Sistema nervioso central. Tratamiento. Tumor de células germinales.
References
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4. Cormenzana Carpio M, Nehme Álvarez D, Hernández Marqúes C, Pérez Martínez A, Lassaletta Atienza A, Madero López L. Tumores germinales intracraneales: revisión de 21 años. An Pediatr. 2016; 86 (1):20-27.
5. Fetcko K, Dey M. Primary Central Nervous System Germ Cell Tumors: A Review and Update. Med Res Arch. 2018;6 (3): 1719.
6. Wong K, Abongwa C, Chang E, Dahll G. Germ Cell Tumors. In: Chang E, Brown P, Lo S, Sahgal A, Suh J, ed. by. Adult CNS Radiation Oncology: Principles and Practice. 1st ed. Cham, Switzerland; 2019. p. 765.
7. Lee S, Jung K, Ha J, Oh C, Kim H, Park H, et al. Nationwide Population-Based Incidence and Survival Rates of Malignant Central Nervous System Germ Cell Tumors in Korea, 2005-2012. Cancer Res Treat. 2017; 49(2):494-501.
8. Mufti S, Jamal A. Primary intracranial germ cell tumors. Asian J Neurosurg. 2012;7(4):197.
9. Cho KT, Wang KC, Kim SK, Shin SH, Chi JG, Cho BK. Pediatric brain tumors: Statistics of SNUH, Korea (1959-2000) Childs Nerv Syst. 2002; 18:30–7.
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26. Sun Y, Liu W, Liu T, Feng X, Yang N, Zhou H. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res. 2015; 35(6):600-604.
27. Vasiljevic A, Szathmari A, Champier J, Fèvre-Montange M, Jouvet A. Histopathology of pineal germ cell tumors. Neurochirurgie. 2015; 61(2-3):130-137.
28. Zapka P, Dörner E, Dreschmann V, Sakamato N, Kristiansen G, Calaminus G et al. Type, Frequency, and Spatial Distribution of Immune Cell Infiltrates in CNS Germinomas: Evidence for Inflammatory and Immunosuppressive Mechanisms. J Neuropathol Exp Neurol. 2018; 77(2):119-127.
29. Miyagawa T, Murai H, Iwadate Y. GERM-02. Immunohistochemical evaluation for the pathogenesis of intracranial germ cell tumors: expression of pluripotency and cell differentiation markers. Neuro Oncol. 2017;19 (suppl_4):iv22-iv22.
30. Tan G, Sallapan S, Haworth K, Finlay J, Boue D, Pierson C. CNS germinoma with extensive calcification: An unusual histologic finding. Malays J Pathol. 2019; 41(1):71-73.
31. Gaillard F, Jones J. Masses of the pineal region: clinical presentation and radiographic features. Postgrad Med J. 2010; 86(1020):597-607.
32. Frappaz D, Pedone C, Thiesse P, Faure-Conter C, Carrie C, Szathmari A et al. P11.05 Visual impairment in intracranial germinomas. Neuro Oncol. 2017; 19(suppl_3):iii92-iii92.
33. Marri R, Rao H, Osorio D, Finlay J. Hearing Loss, Tinnitus and Pineal Germinoma: Parinaud Dorsal Midbrain Syndrome Revisited. Oncogen Journal. 2019;2(1):3.
34. Pierzchlewicz K, Bilska M, Jurkiewicz E, Chmielewski D, Moszczyńska E, Daszkiewicz P et al. Germinoma Mimicking Brain Inflammation: A Case Report. Child Neurol Open. 2019;6: 2329048X19848181.
35. Mesquita Filho P, Santos F, Köhler L, Manfroi G, De Carli F, Augusto de Araujo M et al. Suprasellar Germinomas: 2 Case Reports and Literature Review. World Neurosurg. 2018;117:165-171.
36. Konovalov A, Kadyrov S, Tarasova E, Mazerkina N, Gorelyshev S, Khukhlaeva E et al. Basal ganglia germinomas in children. Four clinical cases and a literature review. Zh Vopr Neirokhir Im N N Burdenko. 2016;80(1):71.
37. Chen Y, Su K, Chang J. Atypical major depressive episode as initial presentation of intracranial germinoma in a male adolescent. Neuropsychiatr Dis Treat. 2016;13:35-40.
38. Ghosh P, Tekautz T, Mitra S. Pearls & Oy-sters: Bifocal germinoma of the brain: Review of systems is key to the diagnosis. Neurology. 2012;78(2):e8-e10.
39. Kubik M, Saremian J. Primary cerebrospinal fluid diagnosis of pineal germinoma. Diagn Cytopathol. 2015;43(6):482-484.
40. Echevarria M, Fangusaro J, Goldman S. Pediatric Central Nervous System Germ Cell Tumors: A Review. Oncologist. 2008;13(6):690-699.
41. Moon W, Chang K, Kim I, Han M, Choi C, Suh D et al. Germinomas of the basal ganglia and thalamus: MR findings and a comparison between MR and CT. AJR Am J Roentgenol. 1994;162(6):1413-1417.
42. Wang Y, Zou L, Gao B. Intracranial germinoma: clinical and MRI findings in 56 patients. Childs Nerv Syst. 2010;26(12):1773-1777.
43. Morana G, Alves C, Tortora D, Finlay J, Severino M, Nozza P et al. T2*-based MR imaging (gradient echo or susceptibility-weighted imaging) in midline and off-midline intracranial germ cell tumors: a pilot study. Neuroradiology. 2017;60(1):89-99.
44. Awa R, Campos F, Arita K, Sugiyama K, Tominaga A, Kurisu K et al. Neuroimaging diagnosis of pineal region tumors—quest for pathognomonic finding of germinoma. Neuroradiology. 2014;56(7):525-534.
45. Sawamura Y, de Tribolet N, Ishii N, Abe H. Management of primary intracranial germinomas: diagnostic surgery or radical resection?. J Neurosurg. 1997;87(2):262-266.
46. Pérez-García J. Germinoma intracraneal, 2 casos en varones adolescentes. Rev Esp Patol. 2007;40(4):239-242.
47. Kubik M, Saremian J. Primary cerebrospinal fluid diagnosis of pineal germinoma. Diagn Cytopathol. 2015;43(6):482-484.
48. Packer RJ, Cohen BH, Cooney K. Intracranial germ cell tumors. The oncologist. 2000;5: 312–320 pmid:10964999
49. Lo A, Hodgson D, Dang J, Tyldesley S, Bouffet E, Bartels U et al. Intracranial Germ Cell Tumors in Adolescents and Young Adults: A 40-Year Multi-Institutional Review of Outcomes. Int J Radiat Oncol Biol Phys. 2019; 0(0).
50. Kobiakov G, Poddubskiy A, Pitskhelauri D, Mazerkina N, Ataf’eva L, Absalyamova O et al. P05.56 Treatment algorithm of patients with primary CNS germinoma: the experience of N.N. Burdenko Neurosurgery Institute. Neuro Oncol. 2018;20(suppl 3):iii316-iii316.
51. Khatua S, Fangusaro J, Dhall G, Boyett J, Wu S, Bartels U. GC-17 The children's oncology group (COG) current treatment approach for children with newly diagnosed central nervous system (CNS) localized germinoma (ACNS1123 STRATUM 2). Neuro Oncol. 2016;18(suppl 3):iii45.4-iii46.
52. Chung S, Han J, Kim D, Yoon H, Suh C. Treatment outcomes based on radiation therapy fields for bifocal germinoma: Synchronous or disseminated disease?. PLoS One. 2019;14(10):e0223481.
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56. Zhang RP, Chen J, Hu XL, Fang YL, Cai CQ. Immature teratoma of the posterior fossa in an infant: case report. Turk Pediatri Ars. 2019;54(2):125-128.
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2. Gómez Vega JC, Ocampo Navia MI, De Vries E, Feo Lee OH. Sobrevida de los tumores cerebrales primarios en Colombia. Univ. Med. 2020; 61(3). https://doi.org/10-11144/Javeriana.umed61-3.s obr
3. Gittleman H, Cioffi G, Osorio D, Finlay J, T V, Kruchko C. Descriptive epidemiology of germ cell tumors of the central nervous system diagnosed in the United States from 2006 to 2015. J Neurooncol. 2019;1–10.
4. Cormenzana Carpio M, Nehme Álvarez D, Hernández Marqúes C, Pérez Martínez A, Lassaletta Atienza A, Madero López L. Tumores germinales intracraneales: revisión de 21 años. An Pediatr. 2016; 86 (1):20-27.
5. Fetcko K, Dey M. Primary Central Nervous System Germ Cell Tumors: A Review and Update. Med Res Arch. 2018;6 (3): 1719.
6. Wong K, Abongwa C, Chang E, Dahll G. Germ Cell Tumors. In: Chang E, Brown P, Lo S, Sahgal A, Suh J, ed. by. Adult CNS Radiation Oncology: Principles and Practice. 1st ed. Cham, Switzerland; 2019. p. 765.
7. Lee S, Jung K, Ha J, Oh C, Kim H, Park H, et al. Nationwide Population-Based Incidence and Survival Rates of Malignant Central Nervous System Germ Cell Tumors in Korea, 2005-2012. Cancer Res Treat. 2017; 49(2):494-501.
8. Mufti S, Jamal A. Primary intracranial germ cell tumors. Asian J Neurosurg. 2012;7(4):197.
9. Cho KT, Wang KC, Kim SK, Shin SH, Chi JG, Cho BK. Pediatric brain tumors: Statistics of SNUH, Korea (1959-2000) Childs Nerv Syst. 2002; 18:30–7.
10. Committee of Brain Tumor Registry of Japan: Report of Brain Tumor Registry of Japan (1969-1996) Neurol Med Chir (Tokyo) 2003; 43(Suppl:i-vii):1–111.
11. Wong TT, Ho DM, Chang KP, Yen SH, Guo WY, Chang FC, et al. Primary pediatric brain tumors: Statistics of Taipei VGH, Taiwan (1975-2004) Cancer. 2005; 104:2156–67.
12. McCarthy B, Shibui S, Kayama T, Miyaoka E, Narita Y, Murakami M et al. Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries. Neuro Oncol. 2012; 14(9):1194-1200.
13. Thakkar J, Chew L, Villano J. Primary CNS germ cell tumors: current epidemiology and update on treatment. Med Oncol. 2013; 30(2).
14. DeWitt J, Mock A, Louis D. The 2016 WHO classification of central nervous system tumors: what neurologists need to know. Curr Opin Neurol. 2017; 30(6):643-649.
15. Nikolic A, Volarevic V, Armstrong L, Lako M, Stojkovic M. Primordial Germ Cells: Current Knowledge and Perspectives. Stem Cells Int. 2016;2016:1-8.
16. Andrews P. Teratocarcinomas and human embryology: Pluripotent human EC cell lines. APMIS. 1998;106(1-6):158-168.
17. Phi J, Wang K, Kim S. Intracranial Germ Cell Tumor in the Molecular Era. J Korean Neurosurg Soc. 2018;61(3):333-342.
18. Chaganti R, Houldsworth J. The cytogenetic theory of the pathogenesis of human adult male germ cell tumors. APMIS. 1998;106(1-6):80-84.
19. Spiller C, Bowles J. Germ cell neoplasia in situ: The precursor cell for invasive germ cell tumors of the testis. Int J Biochem Cell Biol. 2017;86:22-25.
20. Espinosa J, Martínez A, Paniza M, Rull J, Bosch F. Patología tumoral primaria no Astrocitaria del SNC. In SERAM: Sociedad Española de Radiología Médica 2018. URL: https://piper.espacio-seram.com/index.php/seram/article/view/1531. [16.07.2020]
21. Chen R, Tao C, You C, Ju Y. Fast-developing fatal diffuse leptomeningeal dissemination of a pineal germinoma in a young child: a case report and literature review. Br J Neurosurg. 2018:1-8.
22. Lischalk J.W., MacDonald S.M. Pediatric Intracranial Germinomas. In: Terezakis S., MacDonald S. (eds) Target Volume Delineation for Pediatric Cancers. Practical Guides in Radiation Oncology. Springer, Cham. Suiza. 2019. P 55-70.
23. Ventura M, Gomes L, Rosmaninho-Salgado J, Barros L, Paiva I, Melo M et al. Bifocal germinoma in a patient with 16p11.2 microdeletion syndrome. Endocrinol Diabetes Metab Case Rep. 2019; 2019(1).
24. Fukushima S, Yamashita S, Kobayashi H, Takami H, Fukuoka K, Nakamura T et al. Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathol. 2017; 133(3):445-462.
25. Harding A, Cortez-Toledo E, Magner N, Beegle J, Coleal-Bergum D, Hao D et al. Highly Efficient Differentiation of Endothelial Cells from Pluripotent Stem Cells Requires the MAPK and the PI3K Pathways. Stem Cells. 2017; 35(4):909-919.
26. Sun Y, Liu W, Liu T, Feng X, Yang N, Zhou H. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res. 2015; 35(6):600-604.
27. Vasiljevic A, Szathmari A, Champier J, Fèvre-Montange M, Jouvet A. Histopathology of pineal germ cell tumors. Neurochirurgie. 2015; 61(2-3):130-137.
28. Zapka P, Dörner E, Dreschmann V, Sakamato N, Kristiansen G, Calaminus G et al. Type, Frequency, and Spatial Distribution of Immune Cell Infiltrates in CNS Germinomas: Evidence for Inflammatory and Immunosuppressive Mechanisms. J Neuropathol Exp Neurol. 2018; 77(2):119-127.
29. Miyagawa T, Murai H, Iwadate Y. GERM-02. Immunohistochemical evaluation for the pathogenesis of intracranial germ cell tumors: expression of pluripotency and cell differentiation markers. Neuro Oncol. 2017;19 (suppl_4):iv22-iv22.
30. Tan G, Sallapan S, Haworth K, Finlay J, Boue D, Pierson C. CNS germinoma with extensive calcification: An unusual histologic finding. Malays J Pathol. 2019; 41(1):71-73.
31. Gaillard F, Jones J. Masses of the pineal region: clinical presentation and radiographic features. Postgrad Med J. 2010; 86(1020):597-607.
32. Frappaz D, Pedone C, Thiesse P, Faure-Conter C, Carrie C, Szathmari A et al. P11.05 Visual impairment in intracranial germinomas. Neuro Oncol. 2017; 19(suppl_3):iii92-iii92.
33. Marri R, Rao H, Osorio D, Finlay J. Hearing Loss, Tinnitus and Pineal Germinoma: Parinaud Dorsal Midbrain Syndrome Revisited. Oncogen Journal. 2019;2(1):3.
34. Pierzchlewicz K, Bilska M, Jurkiewicz E, Chmielewski D, Moszczyńska E, Daszkiewicz P et al. Germinoma Mimicking Brain Inflammation: A Case Report. Child Neurol Open. 2019;6: 2329048X19848181.
35. Mesquita Filho P, Santos F, Köhler L, Manfroi G, De Carli F, Augusto de Araujo M et al. Suprasellar Germinomas: 2 Case Reports and Literature Review. World Neurosurg. 2018;117:165-171.
36. Konovalov A, Kadyrov S, Tarasova E, Mazerkina N, Gorelyshev S, Khukhlaeva E et al. Basal ganglia germinomas in children. Four clinical cases and a literature review. Zh Vopr Neirokhir Im N N Burdenko. 2016;80(1):71.
37. Chen Y, Su K, Chang J. Atypical major depressive episode as initial presentation of intracranial germinoma in a male adolescent. Neuropsychiatr Dis Treat. 2016;13:35-40.
38. Ghosh P, Tekautz T, Mitra S. Pearls & Oy-sters: Bifocal germinoma of the brain: Review of systems is key to the diagnosis. Neurology. 2012;78(2):e8-e10.
39. Kubik M, Saremian J. Primary cerebrospinal fluid diagnosis of pineal germinoma. Diagn Cytopathol. 2015;43(6):482-484.
40. Echevarria M, Fangusaro J, Goldman S. Pediatric Central Nervous System Germ Cell Tumors: A Review. Oncologist. 2008;13(6):690-699.
41. Moon W, Chang K, Kim I, Han M, Choi C, Suh D et al. Germinomas of the basal ganglia and thalamus: MR findings and a comparison between MR and CT. AJR Am J Roentgenol. 1994;162(6):1413-1417.
42. Wang Y, Zou L, Gao B. Intracranial germinoma: clinical and MRI findings in 56 patients. Childs Nerv Syst. 2010;26(12):1773-1777.
43. Morana G, Alves C, Tortora D, Finlay J, Severino M, Nozza P et al. T2*-based MR imaging (gradient echo or susceptibility-weighted imaging) in midline and off-midline intracranial germ cell tumors: a pilot study. Neuroradiology. 2017;60(1):89-99.
44. Awa R, Campos F, Arita K, Sugiyama K, Tominaga A, Kurisu K et al. Neuroimaging diagnosis of pineal region tumors—quest for pathognomonic finding of germinoma. Neuroradiology. 2014;56(7):525-534.
45. Sawamura Y, de Tribolet N, Ishii N, Abe H. Management of primary intracranial germinomas: diagnostic surgery or radical resection?. J Neurosurg. 1997;87(2):262-266.
46. Pérez-García J. Germinoma intracraneal, 2 casos en varones adolescentes. Rev Esp Patol. 2007;40(4):239-242.
47. Kubik M, Saremian J. Primary cerebrospinal fluid diagnosis of pineal germinoma. Diagn Cytopathol. 2015;43(6):482-484.
48. Packer RJ, Cohen BH, Cooney K. Intracranial germ cell tumors. The oncologist. 2000;5: 312–320 pmid:10964999
49. Lo A, Hodgson D, Dang J, Tyldesley S, Bouffet E, Bartels U et al. Intracranial Germ Cell Tumors in Adolescents and Young Adults: A 40-Year Multi-Institutional Review of Outcomes. Int J Radiat Oncol Biol Phys. 2019; 0(0).
50. Kobiakov G, Poddubskiy A, Pitskhelauri D, Mazerkina N, Ataf’eva L, Absalyamova O et al. P05.56 Treatment algorithm of patients with primary CNS germinoma: the experience of N.N. Burdenko Neurosurgery Institute. Neuro Oncol. 2018;20(suppl 3):iii316-iii316.
51. Khatua S, Fangusaro J, Dhall G, Boyett J, Wu S, Bartels U. GC-17 The children's oncology group (COG) current treatment approach for children with newly diagnosed central nervous system (CNS) localized germinoma (ACNS1123 STRATUM 2). Neuro Oncol. 2016;18(suppl 3):iii45.4-iii46.
52. Chung S, Han J, Kim D, Yoon H, Suh C. Treatment outcomes based on radiation therapy fields for bifocal germinoma: Synchronous or disseminated disease?. PLoS One. 2019;14(10):e0223481.
53. PDQ® Pediatric Treatment Editorial Board. Childhood Central Nervous System Germ Cell Tumors Treatment: Treatment - Health Professional Information [NCI] | CS Mott Children's Hospital | Michigan Medicine. In Mottchildren.org. 2019. URL: https://www.mottchildren.org/health-library/ncicdr0000712041 . [16.07.2020]
54. Fukushima S, Yamashita S, Kobayashi H, et al. Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathol. 2017;133(3):445-462.
55. Sato K, Takeuchi H, Kubota T. Pathology of intracranial germ cell tumors. Prog Neurol Surg. 2009;23:59-75.
56. Zhang RP, Chen J, Hu XL, Fang YL, Cai CQ. Immature teratoma of the posterior fossa in an infant: case report. Turk Pediatri Ars. 2019;54(2):125-128.
57. Urcuqui L. Teratoma congénito gigante de la órbita: reporte de caso. revcolombcancerol. 2015;19(1):53-58.
58. Lacruz C, Saénz de Santamaría J, Bardales R. Germ Cell Tumors. En: Lacruz C, Saénz de Santamaría J, Bardales R, eds. by. Central Nervous System Intraoperative Cytopathology. Essentials in Cytopathology. Springer, Cham; 2018.
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Cómo citar
Marchán Cárdenas, J. C., Visbal Spirko, L. P. ., & Acosta Fernández, S. A. (2021). Tumores de células germinales intracraneales: aspectos básicos, abordaje diagnóstico y alternativas terapéuticas . Universitas Medica, 62(4). https://doi.org/10.11144/Javeriana.umed62-4.tcgi
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