Abstract
Germ cell tumors (GCTs) are a rare group of pediatric brain tumors that occur in the midline and often present with endocrinopathies including central diabetes insipidus (DI) or anterior pituitary deficiencies. Symptoms of central DI may be present in patients for months to years prior to definitive diagnosis. Patients may require long-term serial imaging and monitoring of tumor markers to ensure appropriate diagnosis and treatment. Germ cell tumors are subdivided into germinomas and nongerminomatous germ cell tumors (NGGCT) based on histology and tumor markers. Germinomas are quite radiosensitive, and historically have been treated with radiation therapy alone. NGGCTs are less responsive to radiation and require a more aggressive treatment approach with the addition of chemotherapy and sometimes surgery. Due to the complexities of diagnosis and management, these patients require a multidisciplinary approach to management including endocrinology, neurosurgery, neuro-oncology, radiation oncology, and neuro-ophthalmology.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Zong Z, Wang Y, Dai C, et al. Central nervous system germ cell tumors: a review of the literature. J Child Neurol. 2018;33(9):610–20.
Fujimaki T. Central nervous system germ cell tumors: classification, clinical features, and treatment with a historical overview. J Child Neurol. 2009;24(11):1439–45.
Phi JH, Wang KC, Kim SK. Intracranial germ cell tumors in the molecular era. J Korean Neurosurg Soc. 2018;61(3):333–42.
Di Lorgi N, Morana G, Maghnie M. Pituitary Stalk thickening on MRI: when is the best time to re-scan and how long should we continue re-scanning for? Clin Endocrinol. 2015;83:449–55.
Di Lorgi N, Allegri AE, Napoli F, et al. Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases. J Clin Endocrinol Metab. 2014;99(4):1264–72.
Corredor Andrés B, Muñoz Calvo MT, López Pino MA, et al. Thickening of pituitary stalk in children and adolescents with central diabetes insipidus: causes and consequences. An Pediatr (Engl Ed). 2019;90(5):293–300.
Leger J, Velasquez A, Garel C, Hassan M, Czernichow P. Thickened pituitary stalk on magnetic resonance imaging in children with central diabetes insipidus. J Clin Endocrinol Metabol. 1999;84(6):1954–60.
Louis D, Perry A, Reifenerger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–20.
Bowzky Al-Naeeb A, Murray A, Horan G, et al. Current management of intracranial germ cell tumours. Clin Oncol. 2018;30:204–14.
Murray M, Bartels U, Nishikawa R, et al. Consensus on the management of intracranial germ-cell tumours. Lancet Oncol. 2015;16:470–7.
Robison NJ, Prabhu SP, Sun P, et al. Predictors of neoplastic disease in children with isolated pituitary stalk thickening. Pediatr Blood Cancer. 2013;60:1630–5.
Catford S, Yuen Wang Y, Wong R. Pituitary stalk lesions: systematic review and clinical guidance. Clin Endocrinol. 2016;85:507–21.
Bamberg M, Kortmann RD, Calaminus G, Becker G, Meisner C, Harms D, et al. Radiation therapy for intracranial germinoma: results of the German cooperative prospective trials MAKEI 83/86/89. J Clin Oncol. 1999;17(8):2585–92.
Shirato H, Nishio M, Sawamura Y, et al. Analysis of long-term treatment of intracranial germinoma. Int J Radiat. Oncol Biol Phys. 1997;37(3):511–5.
Merchant TE, Sherwood SH, Mulhern RK, Rose SR, Thompson SJ, Sanford RA, Kun LE. CNS germinoma: disease control and long-term functional outcome for 12 children treated with craniospinal irradiation. Int J Radiat Oncol Biol Phys. 2000;46(5):1171–6.
Packer RJ, Sutton LN, Atkins TE, Radcliffe J, Bunin GR, D’Angio G, Siegel KR, Schut L. A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg. 1989;70(5):707–13.
Balmaceda C, Heller G, Rosenblum M, et al. Chemotherapy without irradiation—a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study. J Clin Oncol. 1996;14:2908–15.
Calaminus G, Kortmann R-D, Worch J, Nicholson JC, Alapetite C, Garre ML, et al. SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease. Neuro-Oncology. 2013;15:788–96.
Kellie SJ, Boyce H, Dunkel IJ, et al. Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach. Pediatr Blood Cancer. 2004;43(2):126–33.
Alapetite C, Brisse H, Patte C, Raquin MA, Gaboriaud G, Carrie C, et al. Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience. Neuro-Oncology. 2010;12(12):1318–25.
Rogers SJ, Mosleh-Shirazi MA, Saran FH. Radiotherapy of localised intracranial germinoma: time to sever historical ties? Lancet Oncol. 2005;6:509–19.
Aoyama H, Shirato H, Yoshia H, et al. Retrospective multi-institutional study of radiotherapy for intracranial nongerminomatous germ cell tumors. Radiother Oncol. 1998;49:55–9.
Calaminus G, Bamberg M, Jürgens H, Kortmann RD, Sörensen N, Wiestler OD, Göbel U. Impact of surgery, chemotherapy and irradiation on long term outcome of intracranial malignant non-germinomatous germ cell tumors: results of the German Cooperative Trial MAKEI 89. Klin Padiatr. 2004;216(3):141–9.
Goldman S, Bouffet E, Fisher PG, Allen JC, Robertson PL, Chuba PJ, Donahue B, Kretschmar CS, Zhou T, Buxton AB, Pollack IF. Phase II trial assessing the ability of neoadjuvant chemotherapy with or without second-look surgery to eliminate measurable disease for nongerminomatous germ cell tumors: a children’s Oncology Group Study. J Clin Oncol. 2015;33(22):2464–71.
Abu Arja MH, Boufett E, Finlay JL, AbdelBaki MS. Critical Review of the management of primary central nervous nongerminomatous germ cell tumors. Pediatr Blood Cancer. 2019;16:e27658.
Kim J, Park J. Understanding the treatment strategies of intracranial germ cell tumors: focusing on radiotherapy. J Korean Neurosurg Soc. 2015;57(5):315–22.
Fangusaro J, Wu S, MacDonald S, et al. Phase II trial of response-based radiation therapy for patients with localized CNS nongerminomatous germ cell tumors: a children’s Oncology Group Study. J Clin Oncol. 2019;37(34):3283–90.
Liang SY, Yang TF, Chen YW, Liang ML, Chen HH, Chang KP, Shan IK, Chen YS, Wong TT. Neuropsychological functions and quality of life in survived patients with intracranial germ cell tumors after treatment. Neuro-Oncology. 2013;15(11):1543–51.
Wang L, Yamaguchi S, Burstein M, et al. Novel somatic and germline mutations in intracranial germ cell tumours. Nature. 2014;511(7508):241–5.
Fukushima S, Otsuka A, Suzuki T, et al. Mutually exclusive mutations of KIT and RAS are associated with KIT mRNA expression and chromosomal instability in primary intracranial pure germinomas. Acta Neuropathol. 2014;127(6):911–25.
Ichimura K, Fukushima S, Totoki Y, et al. Recurrent neomorphic mutations of MTOR in central nervoussystem and testicular germ cell tumors may be targeted for therapy. Acta Neuropathol. 2016;131(6):889–901.
Tamaki H, Fukuoka K, Fukushima S, et al. Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium. Neuro-Oncology. 2019;21(12):1565–77.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Desai, K., Fisher, M.J. (2021). Germ Cell Tumors. In: Alter, C.A. (eds) Diabetes Insipidus in Children. Springer, Cham. https://doi.org/10.1007/978-3-030-83248-3_6
Download citation
DOI: https://doi.org/10.1007/978-3-030-83248-3_6
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-83247-6
Online ISBN: 978-3-030-83248-3
eBook Packages: MedicineMedicine (R0)