颅内生殖细胞肿瘤是一种好发于儿童及青少年的罕见肿瘤,常位于颅内松果体区、蝶鞍区和基底节区。组织类型通常分为生殖细胞瘤和非生殖细胞性生殖细胞肿瘤。临床表现与病变位置和大小相关。诊断分为临床诊断和活检病理诊断。治疗主要是放化疗和手术结合。新型肿瘤标志物MiroRNA (MiRNA)将来可能用于颅内生殖细胞肿瘤的诊断与治疗后评估。组织病理及分子病理的明确可为颅内生殖细胞肿瘤的分型及患者靶向治疗提供依据。本文对颅内生殖细胞瘤的发展现况及诊疗进展作一综述。 Intracranial germ cell tumors (IGCTs) are uncommon tumours occurring in children and young adults with a tendency to appear in pineal, suprasellar and basal ganglia region. They are usually segregated into germinomas and nongerminomatous tumours (NGGCTs). The main clinical mani-festations of the tumors depend on their size and location. The diagnosis has been divided into clinical diagnosis and surgical biopsy pathology diagnosis. The tumor therapy regimen is mostly chemoradiotherapy and surgery. New tumor markers microRNA (MiRNA) may be potentially val-uable biomarkers in the diagnosis and evaluation of treatment of intracranial germ cell tumors in the future. Histopathology and molecular analyses are attempting to further specify the different IGCTs subtypes and are helping to direct the development of distinct therapeutic targets to improve treatment and prognosis. Here is to make a review of the current status and management in intracranial germ cell tumors
高晓红,王亚明,白茫茫. 颅内生殖细胞肿瘤研究进展 Study Progress of Intracranial Germ Cell Tumors[J]. 临床医学进展, 2020, 10(03): 270-278. https://doi.org/10.12677/ACM.2020.103043
参考文献ReferencesMakino, K., Nakamura, H., Yano, S., et al. (2013) Incidence of Primary Central Nervous System Germ Cell Tumors in Childhood: A Regional Survey in Kumamoto Prefecture in Southern Japan. Pediatric Neurosurgery, 49, 155-158.
<br>https://doi.org/10.1159/000358806Wong, T.T., Ho, D.M., Chang, K.P., et al. (2005) Primary Pediatric Brain Tumors: Statistics of Taipei VGH, Taiwan (1975-2004). Cancer, 104, 2156-2167. <br>https://doi.org/10.1002/cncr.21430Foo, A.S., Lim, C., Chong, D.Q., et al. (2014) Primary Intracranial Germ Cell Tumours: Experience of a Single South-East Asian Institution. Journal of Clinical Neuroscience, 21, 1761-1766.
<br>https://doi.org/10.1016/j.jocn.2014.01.021Makino, K., Nakamura, H., Yano, S., et al. (2010) Popula-tion-Based Epidemiological Study of Primary Intracranial Tumors in Childhood. Child’s Nervous System, 26, 1029-1034. <br>https://doi.org/10.1007/s00381-010-1126-xMccarthy, B.J., Shibui, S., Kayama, T., et al. (2012) Primary CNS Germ Cell Tumors in Japan and the United States: An Analysis of 4 Tumor Registries. Neuro-Oncology, 14, 1194-1200. <br>https://doi.org/10.1093/neuonc/nos155Matsutani, M. (2001) Combined Chemotherapy and Radiation Therapy for CNS Germ Cell Tumors: The Japanese Experience. Journal of Neuro-Oncology, 54, 311-316. <br>https://doi.org/10.1023/A:1012743707883Lee, S.H., Jung, K.W., Ha, J., et al. (2017) Nationwide Popula-tion-Based Incidence and Survival Rates of Malignant Central Nervous System Germ Cell Tumors in Korea, 2005-2012. Cancer Research and Treatment, 49, 494-501.
<br>https://doi.org/10.4143/crt.2016.129Louis, D.N., Perry, A., Reifenberger, G., et al. (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary. Acta Neuropathologica, 131, 803-820.
<br>https://doi.org/10.1007/s00401-016-1545-1Packer, R.J., Cohen, B.H. and Cooney, K. (2000) Intracranial Germ Cell Tumors. Oncologist, 5, 312-320.
<br>https://doi.org/10.1634/theoncologist.2000-0312Fukushima, S., Yamashita, S., Kobayashi, H., et al. (2017) Genome-Wide Methylation Profiles in Primary Intracranial Germ Cell Tumors Indicate a Primordial Germ Cell Origin for Germinomas. Acta Neuropathologica, 133, 445-462.
<br>https://doi.org/10.1007/s00401-017-1673-2Huang X, Zhang R, Mao Y, et al. (2016) Recent Advances in Molecular Biology and Treatment Strategies for Intracranial Germ Cell Tumors. World Journal of Pediatrics, 12, 275-282. <br>https://doi.org/10.1007/s12519-016-0021-2Tan, C. and Scotting, P.J. (2013) Stem Cell Research Points the Way to the Cell of Origin for Intracranial Germ Cell Tumours. The Journal of Pathology, 229, 4-11. <br>https://doi.org/10.1002/path.4098Lee, S.H., Appleby, V., Jeyapalan, J.N., et al. (2011) Variable Methylation of the Imprinted Gene, SNRPN, Supports a Relationship between Intracranial Germ Cell Tumours and Neural Stem Cells. Journal of Neuro-Oncology, 101, 419-428. <br>https://doi.org/10.1007/s11060-010-0275-9Echevarria, M.E., Fangusaro, J. and Goldman, S. (2008) Pediatric Central Nervous System Germ Cell Tumors: A Review. Oncologist, 13, 690-699. <br>https://doi.org/10.1634/theoncologist.2008-0037Wu, C.C., Guo, W.Y., Chang, F.C., et al. (2017) MRI Features of Pediatric Intracranial Germ Cell Tumor Subtypes. Journal of Neuro-Oncology, 134, 221-230. <br>https://doi.org/10.1007/s11060-017-2513-xCheng, S., Kilday, J.P., Laperriere, N., et al. (2016) Outcomes of Children with Central Nervous System Germinoma Treated with Multi-Agent Chemotherapy Followed by Reduced Radiation. Journal of Neuro-Oncology, 127, 173-180.
<br>https://doi.org/10.1007/s11060-015-2029-1Takami H, Fukuoka K, Fukushima S, et al. (2019) Integrated Clinical, Histopathological, and Molecular Data Analysis of 190 Central Nervous System Germ Cell Tumors from the iGCT Consortium. Neuro-Oncology, 21, 1565-1577.
<br>https://doi.org/10.1093/noajnl/vdz039.175Murray, M.J., Nicholson, J.C. and Coleman, N. (2015) Biology of Childhood Germ Cell Tumours, Focusing on the Significance of microRNAs. Andrology, 3, 129-139. <br>https://doi.org/10.1111/andr.277Palmer, R.D., Murray, M.J., Saini, H.K., et al. (2010) Malignant Germ Cell Tumors Display Common microRNA Profiles Resulting in Global Changes in Expression of Messenger RNA Targets. Cancer Research, 70, 2911-2923.
<br>https://doi.org/10.1158/0008-5472.CAN-09-3301Murray, M.J., Bartels, U., Nishikawa, R., et al. (2015) Consensus on the Management of Intracranial Germ-Cell Tumours. The Lancet Oncology, 16, e470-e477. <br>https://doi.org/10.1016/S1470-2045(15)00244-2Gao, Y., Jiang, J. and Liu, Q. (2014) Clinicopathological and Immunohistochemical Features of Primary Central Nervous System Germ Cell Tumors: A 24-Years Experience. International Journal of Clinical and Experimental Pathology, 7, 6965-6972.Fukushima, S., Otsuka, A., Suzuki, T., et al. (2014) Mutually Exclusive Mutations of KIT and RAS Are Associated with KIT mRNA Expression and Chromosomal Instability in Primary Intracranial Pure Germinomas. Acta Neuropathologica, 127, 911-925. <br>https://doi.org/10.1007/s00401-014-1247-5Bosl, G.J., Ilson, D.H., Rodriguez, E., et al. (1994) Clinical Relevance of the i(12p) Marker Chromosome in Germ Cell Tumors. Journal of the National Cancer Institute, 86, 349-355. <br>https://doi.org/10.1093/jnci/86.5.349Sukov, W.R., Cheville, J.C., Giannini, C., et al. (2010) Isochromosome 12p and Polysomy 12 in Primary Central Nervous System Germ Cell Tumors: Frequency and Associ-ation with Clinicopathologic Features. Human Pathology, 41, 232-238. <br>https://doi.org/10.1016/j.humpath.2009.07.017Schneider, D.T., Zahn, S., Sievers, S., et al. (2006) Molecular Genetic Analysis of Central Nervous System Germ Cell Tumors with Comparative Genomic Hybridization. Modern Pathology, 19, 864-873.
<br>https://doi.org/10.1038/modpathol.3800607Robertson, P.L., Jakacki, R., Hukin, J., et al. (2014) Multimo-dality Therapy for CNS Mixed Malignant Germ Cell Tumors (MMGCT): Results of a Phase II Multi-Institutional Study. Journal of Neuro-Oncology, 118, 93-100.
<br>https://doi.org/10.1007/s11060-013-1306-0Afzal, S., Wherrett, D., Bartels, U., et al. (2010) Challenges in Management of Patients with Intracranial Germ Cell Tumor and Diabetes Insipidus Treated with Cisplatin and/or Ifosfamide Based Chemotherapy. Journal of Neuro-Oncology, 97, 393-399. <br>https://doi.org/10.1007/s11060-009-0033-zAl-Hussaini, M., Sultan, I., Abuirmileh, N., et al. (2009) Pineal Gland Tumors: Experience from the SEER Database. Journal of Neuro-Oncology, 94, 351-358. <br>https://doi.org/10.1007/s11060-009-9881-9Wong, K., Opimo, A.B., Olch, A.J., et al. (2016) Re-irradiation of Recurrent Pineal Germ Cell Tumors with Radiosurgery: Report of Two Cases and Review of Literature. Cureus, 8, e585. <br>https://doi.org/10.7759/cureus.585Claude, L., Faure-Conter, C., Frappaz, D., et al. (2015) Radiation Therapy in Pediatric Pineal Tumors. Neurochirurgie, 61, 212-215. <br>https://doi.org/10.1016/j.neuchi.2014.11.002Bouffet, E., Baranzelli, M.C., Patte, C., et al. (1999) Combined Treatment Modality for Intracranial Germinomas: Results of a Multicentre SFOP Experience. Societe Francaise d’Oncologie Pediatrique. British Journal of Cancer, 79, 1199-1204. <br>https://doi.org/10.1038/sj.bjc.6690192Malogolowkin, M.H., Krailo, M., Marina, N., et al. (2013) Pilot Study of Cisplatin, Etoposide, Bleomycin, and Escalating Dose Cyclophosphamide Therapy for Children with High Risk Germ Cell Tumors: A Report of the Children’s Oncology Group (COG). Pediatric Blood & Cancer, 60, 1602-1605. <br>https://doi.org/10.1002/pbc.24601Fukuoka, K., Yanagisawa, T., Suzuki, T., et al. (2015) Malignant Transformation of Germinoma 14 Years after Onset: Favorable Efficacy of Oral Etoposide. Pediatrics International, 57, 483-486. <br>https://doi.org/10.1111/ped.12559Frappaz, D., Conter, C.F., Szathmari, A., et al. (2015) The Management of Pineal Tumors as a Model for a Multidisciplinary Approach in Neuro-Oncology. Neurochirurgie, 61, 208-211. <br>https://doi.org/10.1016/j.neuchi.2014.03.003Jinguji, S., Yoshimura, J., Nishiyama, K., et al. (2015) Long-Term Outcomes in Patients with Pineal Nongerminomatous Malignant Germ Cell Tumors Treated by Radical Resection during Initial Treatment Combined with Adjuvant Therapy. Acta Neurochirurgica, 157, 2175-2183. <br>https://doi.org/10.1007/s00701-015-2614-2Dufour, C., Guerrini-Rousseau, L. and Grill, J. (2014) Central Nervous System Germ Cell Tumors: An Update. Current Opinion in Oncology, 26, 622-626. <br>https://doi.org/10.1097/CCO.0000000000000140Huang, X., Zhang, R. and Zhou, L.F. (2009) Diagnosis and Treatment of Intracranial Immature Teratoma. Pediatric Neurosurgery, 45, 354-360. <br>https://doi.org/10.1159/000257524Matsutani, M., Sano, K., Takakura, K., et al. (1997) Primary Intracranial Germ Cell Tumors: A Clinical Analysis of 153 Histologically Verified Cases. Journal of Neurosurgery, 86, 446-455. <br>https://doi.org/10.3171/jns.1997.86.3.0446Calaminus, G., Frappaz, D., Kortmann, R.D., et al. (2017) Out-come of Patients with Intracranial Non-Germinomatous Germ Cell Tumors-Lessons from the SIOP-CNS-GCT-96 Trial. Neuro-Oncology, 19, 1661-1672.
<br>https://doi.org/10.1093/neuonc/nox122Kim, J.W., Kim, W.C., Cho, J.H., et al. (2012) A Multimodal Ap-proach Including Craniospinal Irradiation Improves the Treatment Outcome of High-Risk Intracranial Nongerminomatous Germ Cell Tumors. International Journal of Radiation Oncology, Biology, Physics, 84, 625-631. <br>https://doi.org/10.1016/j.ijrobp.2011.12.077Kochi, M., Itoyama, Y., Shiraishi, S., et al. (2003) Successful Treatment of Intracranial Nongerminomatous Malignant Germ Cell Tumors by Administering Neoadjuvant Chemo-therapy and Radiotherapy before Excision of Residual Tumors. Journal of Neurosurgery, 99, 106-114. <br>https://doi.org/10.3171/jns.2003.99.1.0106Herrada-Pineda, T., Revilla-Pacheco, F. and Manrique-Guzman, S. (2015) Endoscopic Approach for the Treatment of Pineal Region Tumors. Journal of Neurological Surgery Part A: Central European Neurosurgery, 76, 8-12.
<br>https://doi.org/10.1055/s-0032-1330958Li, W., Zhang, B., Kang, W., et al. (2015) Gamma Knife Radiosur-gery (GKRS) for Pineal Region Tumors: A Study of 147 Cases. World Journal of Surgical Oncology, 13, 304. <br>https://doi.org/10.1186/s12957-015-0720-5Gardner, S.L. (2004) Application of Stem Cell Transplant for Brain Tumors. Pediatric Transplantation, 8, 28-32.
<br>https://doi.org/10.1111/j.1398-2265.2004.00202.xWang, L., Yamaguchi, S., Burstein, M.D., et al. (2014) Novel Somatic and Germline Mutations in Intracranial Germ Cell Tumours. Nature, 511, 241-245. <br>https://doi.org/10.1038/nature13296Osorio, D.S., Finlay, J.L., Dhall, G., et al. (2013) Feasibility of Dasatinib in Children and Adolescents with New or Recurrent Central Nervous System Germinoma. Pediatric Blood & Cancer, 60, E100-E102.
<br>https://doi.org/10.1002/pbc.24567Nakamura, H., Makino, K., Kochi, M., Ushio, Y. and Kuratsu, J. (2011) Evaluation of Neoadjuvant Therapy in Patients with Nongerminomatous Malignant Germ Cell Tumors. Journal of Neurosurgery: Pediatrics, 7, 431-438.
<br>https://doi.org/10.3171/2011.1.PEDS10433