• Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 4  |  Issue : 5  |  Page : 134-142

Challenges and advances in the management of pediatric intracranial germ cell tumors: A case report and literature review


1 Department of Paediatric Oncology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK
2 Department of Paediatric Oncology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH; Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

Date of Web Publication30-Oct-2018

Correspondence Address:
Dr. Gerard Cathal Millen
Department of Paediatric Oncology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH
UK
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ctm.ctm_36_17

Rights and Permissions
  Abstract 


Intracranial germ cell tumors are a heterogeneous group of tumors, broadly classified into germinomatous, nongerminomatous, or teratoma subtypes. Treatment has evolved over recent decades to include multimodal therapy combining surgery, radiotherapy, and chemotherapy. Although the majority of intracranial germs cell tumors are treated successfully, management can be fraught with complexities and present significant clinical challenges. Bifocal disease is well described, but rare, and therefore its behavior is not well characterized, particularly in nongerminomatous disease. This case report presents an interesting case, with both rare and common complications, in particular, to emphasize the challenges of germ cell tumor management. With a focus on bifocal disease, we review the published cases and highlight how advanced imaging and magnetic resonance spectroscopy can be used in management. Advances in biology, targeted agents, and novel diagnostic tools are also discussed.

Keywords: Bifocal disease, functional imaging, growing teratoma syndrome, intracranial germ cell tumors, relapse


How to cite this article:
Millen GC, Manias KA, Peet AC, Adamski JK. Challenges and advances in the management of pediatric intracranial germ cell tumors: A case report and literature review. Cancer Transl Med 2018;4:134-42

How to cite this URL:
Millen GC, Manias KA, Peet AC, Adamski JK. Challenges and advances in the management of pediatric intracranial germ cell tumors: A case report and literature review. Cancer Transl Med [serial online] 2018 [cited 2018 Nov 21];4:134-42. Available from: http://www.cancertm.com/text.asp?2018/4/5/134/244520




  Introduction Top


Intracranial germ cell tumors (iGCTs) are a heterogeneous group of tumors classified by the World Health Organization into (1) germinomas, (2) embryonal carcinomas, (3) yolk sac tumors, (4) choriocarcinomas, (5) teratomas, and (6) mixed germ cell tumors.[1],[2] A more practical, treatment-based classification divides iGCTs into three groups: (1) germinomas, (2) nongerminomatous germ cell tumors (NGGCTs), and (3) teratomas. Clinical management of these rare tumors can be difficult. We present a case that highlights some of the common and rarer challenges including bifocal disease, growing teratoma syndrome (GTS) and the management of relapsed disease. We also discuss the use of novel imaging techniques and other diagnostic tools as well as the use of targeted therapies. Fully informed consent was obtained from the family.


  Case Report Top


A 10-year-old boy presented with worsening squint, intermittent, severe headaches, polydipsia, polyuria, behavioral change, and increasing lethargy. Examination revealed papilledema, a 6th cranial nerve palsy, Parinaud's syndrome, and advanced puberty. Magnetic resonance imaging (MRI) revealed two midline tumors, suprasellar and pineal [Figure 1]. Appearances were consistent with that of a germ cell tumor. Diffusion-weighted imaging (DWI) and[1] H-magnetic resonance spectroscopy (MRS) showed that the two components displayed very different profiles [Figure 2]. There were no malignant cells in the cerebrospinal fluid (CSF). Serum and CSF tumor markers showed raised α-fetoprotein (AFP) (76 and 8 kU/L, respectively) and β-human chorionic gonadotropin (β-HCG) (31 and 7 iU/L, respectively). The imaging and tumor markers were consistent with a diagnosis of an NGGCT.
Figure 1: Magnetic resonance imaging at presentation. (a) T2-weighted axial image showing suprasellar and pineal tumors. (b) T1-weighted sagittal images showing both tumors

Click here to view
Figure 2: 1H-magnetic resonance spectroscopy at presentation showing marked differences between the suprasellar and pineal lesions. (a) Suprasellar lesion showing high choline and creatine peaks. (b) Pineal lesion showing predominant lipid peak

Click here to view


Treatment commenced on the SIOP CNS GCT II trial (cisplatin, etoposide and ifosfamide chemotherapy [PEI], surgical resection, and focal radiotherapy). During the first cycle, the patient rapidly deteriorated with reduced consciousness. The size of the suprasellar tumor was significantly increased on imaging, however, the pineal aspect had resolved [Figure 3]. Urgent surgical debulking was undertaken and histology showed mostly mature teratomatous tissue, in keeping with GTS. Of note, focal AFP staining gave suspicion of small foci of yolk sac tumor. Modification to the chemotherapy regimen was required due to brittle diabetes insipidus (DI) and fluid shifts, altered neurological state, and renal toxicity. Despite this, a good treatment response was observed and tumor markers normalized. Resection of the suprasellar residual disease carried unacceptable morbidity; therefore, the patient received a dose of 54 Gy through proton radiotherapy, with the field encompassing the pineal and suprasellar region, while sparing the whole ventricles.
Figure 3: T2-weighted magnetic resonance images showing marked increase in the suprasellar element of the tumor. (a) Axial. (b) Sagittal

Click here to view


Five months later, the patient presented with increased vomiting, headache, and hypernatremia. Serum tumor markers were raised (AFP 117 ikU/mL and β-HCG 28 iU/L) and imaging confirmed relapse with two new foci of disease in the posterior fossa obex and right parietal shunt tract (both outside the radiation field) [Figure 4]. Reinduction chemotherapy with GemPOX (gemcitabine, paclitaxel, and oxaliplatin) was prescribed.[3] Both metastatic lesions decreased in size before stabilizing. The residual at the obex was excised and histology showed mature teratoma with no evidence of malignant disease. Treatment was consolidated with high-dose thiotepa and etoposide with stem cell rescue, followed by 36 Gy delivered through craniospinal irradiation (CSI). At the time of completion, tumor markers remained negative and residual abnormalities stable.
Figure 4: T2-weighted magnetic resonance imaging at relapse showing two new foci of disease at the obex (a) and the right parietal shunt tract (b)

Click here to view


Four months following the salvage treatment, although prognosis remains poor, the patient is conceivably cured. He has pan-hypopituitarism, hypothalamic damage, and little functional vision. His neurocognition is markedly affected and his memory and processing skills are poor. The prospect of an independent life is slight.


  Discussion Top


Intracranial germ cell tumors

iGCTs comprise 3% of pediatric brain tumors in the West and up to 15% in Asia.[4],[5],[6],[7] Germinomas occur twice as often as NGGCTs.[4],[6],[8],[9] In general, iGCTs are predominantly midline tumors arising in the pineal and suprasellar regions but also occur in the basal ganglia, third ventricle, thalamus, and cerebral hemispheres.[8],[10] While presentation may occur at any age, the incidence is highest in the first two decades of life, with the median reported age ranging from 13 to 14.[5],[10],[11] A strong male preponderance of 2–7:1 is seen in all iGCTs, but particularly in pineal tumors (11.5:1).[4],[6],[12] Presentation typically depends on tumor location. Pineal lesions commonly have raised intracranial pressure (ICP), hydrocephalus, and Parinaud's syndrome caused by dorsal midbrain compression.[13],[14] Suprasellar lesions can present insidiously and rarely exhibit raised ICP. Endocrinological abnormalities are common, particularly DI. This can be present before radiologically detectable disease.[15] Growth hormone deficiency, precocious puberty, delayed sexual development, and menstrual irregularities can also occur. Despite treatment, endocrinopathies, especially DI, usually persist and cause considerable morbidity.[15],[16],[17] Diagnosis may be significantly delayed following the onset of symptoms.[18] Loss of vision is caused by direct compression of the visual pathways, hydrocephalus-related optic atrophy, or as a side effect of surgery.[19] Behavioral or psychiatric disturbances are common secondary to protracted endocrine deficiencies or direct tumor infiltration of the basal ganglia or hypothalamus.[20]

Imaging plays a central role in the diagnosis and management of iGCT. Although conventional imaging is rarely sufficient for diagnosis, characteristic features facilitate differentiation from other central tumors and between histological subtypes.[21] Germinomas usually demonstrate homogeneous enhancement, whereas NGGCTs enhance heterogeneously. Advances in imaging herald the development of several techniques that provide additional information about tissue characteristics, including DWI MRI and[1] H-MRS, which begin to be used to improve noninvasive diagnoses. DWI provides information about tissue cellularity through measuring the microscopic rate of water diffusion in tissue.[21],[22],[23],[24] As germinomas are highly cellular, most demonstrate significantly restricted diffusion compared to NGGCTs.[25],[26] MRS provides information about tissue metabolites, such as choline (membrane synthesis), N-acetylaspartate (neuronal marker), and mobile lipids (apoptosis and necrosis).[27] This is presented as a graphical spectrum characteristic of tumor type [Figure 5]. In general, iGCTs have significantly higher lipid and macromolecule concentrations relative to other tumors. Germinomas are characterized by very high lipid and total choline levels and the presence of taurine.[28] Teratomas have significantly lower total choline and creatine levels than germinomas, with high lipids reflecting intratumoral fat.[28],[29]
Figure 5: Example of1H-magnetic resonance spectroscopy with different markers labeled

Click here to view


Currently, the diagnosis of iGCT is approached by surgery or the assessment of tumor markers. A tissue diagnosis, through biopsy or a more aggressive surgical approach, is the accepted method of diagnosis in germinomas. Surgery, however, risks significant morbidity.[30] Scrutiny of tumor markers allows diagnosis without surgery in some patients, specifically NGGCTs. Up to 85% of NGGCTs secrete one or more of the three main tumor markers: AFP, β-HCG, and placental alkaline phosphatase.[31],[32] Pure germinomas do not secrete any tumor markers, although some germinomas contain syncytiotrophoblastic cells, which secrete low levels of β-HCG. As tumor markers are raised in CSF and serum, both of them are assessed.[2],[33],[34] Most experts consider an AFP level of >10 ng/mL diagnostic of NGGCT.[35],[36],[37] β-HCG is more controversial. In the West, β-HCG higher than 50 mIU/mL is currently diagnostic of NGGCT without a biopsy.[11] In Japan, a more liberal β-HCG cutoff is applied up to 200 mIU/mL if the histology is in keeping with a germinoma. No difference in outcome has been reported for patients treated in this fashion.[34],[38],[39]

Prognosis of iGCT is based mainly on histology. Clear evidence supports a worse prognosis for NGGCTs than germinomas (5-year overall survival [OS] 50%–56% vs. 84%–100%, respectively).[37],[40],[41] Treatment combines surgery, chemotherapy, and radiotherapy. The chosen approach depends on the histology and geographical location. For example, in the East, up-front surgery is performed, whereas in the West, limited surgery for diagnostic purposes is favored.[11],[30],[42] Achieving a complete response (CR), either by initial total resection or by the removal of residual tumor after neoadjuvant therapy, is directly related to outcome.[5],[43],[44] The exception is intracranial teratomas, where the preferred treatment is surgical excision, as adjuvant or neoadjuvant therapy has no proven efficacy.[2],[45]

For many decades, radiotherapy has been the backbone of treatment for iGCTs. Germinomas are exquisitely radiosensitive, with a 5-year OS of over 90% with craniospinal radiotherapy alone.[10],[38],[46] Although cure rates are excellent, long-term morbidity and mortality have led to attempts to omit or reduce radiation fields raising several clear points. CSI has a role but can be limited to metastatic or relapsed disease.[10],[38],[46] Radiotherapy is an essential component in treatment and the elimination of radiotherapy altogether has been shown to result in high relapse rates (up to 50%).[37],[41] In germinoma, tumor bed radiotherapy leads to unacceptable rates of ventricular relapses, therefore, the recommended field for germinomas is whole ventricular radiotherapy (WVI).[10],[11],[47] NGGCTs are less radiosensitive and a higher dose (54 Gy) is often prescribed.[48] The optimal field is disputed. In Europe, focal tumor bed radiation is given, based on the relatively few distant relapses. In Japan, NGGCTs stratify as high risk and therefore receive CSI, whereas WVI is used in the current ANCS1123 trial. CSI is recommended for metastatic lesions.[33],[49],[50],[51]

The OS in patients with germinoma is excellent with or without chemotherapy. Adjuvant chemotherapy is, therefore, used to reduce the radiation dose or field and the associated morbidity while maintaining the excellent OS.[52] Regarding NGGCTs, chemotherapy is fundamental to improved survival.[37],[41],[49] Commonly used agents include carboplatin, cisplatin, etoposide, bleomycin, cyclophosphamide, and ifosfamide.[10],[36],[41],[43] Data show that the dose and field of radiotherapy can be safely reduced in both germinomas and NGGCTs treated with concurrent chemotherapy. High-dose chemotherapy with autologous stem cell rescue (HDC + AuSCR) has shown promise, albeit mainly in the context of relapsed disease, and is being investigated in Europe and North America in high risk, poorly responsive disease.[40],[53],[54],[55]

Bifocal or metastatic disease?

Bifocal iGCTs are described as simultaneously occurring tumors in the suprasellar and pineal region and are well-recognized phenomenon. First described in 1974 as “double midline intracranial atypical teratomas,” the main controversy in management is whether they represent localized metasynchronous tumors or metastatic disease, thus dictating the most appropriate management.[56]

The typical appearance of bifocal disease on an MRI scan is considered so archetypical that, in the absence of tumor markers, a diagnosis of germinoma is accepted without biopsy.[57],[58] Bifocal NGGCT is diagnosed if tumor markers are raised. However, other tumors are reported, including histologically confirmed NGGCT with negative markers and metastatic malignant embryonal tumors.[57],[59]

Bifocal disease occurs in approximately 20% of iGCTs, the majority of which are germinomas [Table 1]. Most studies only state the occurrence, rather than describe the behavior of individual cases, and therefore specific demographics are not well known. When described, there are typically no discernable differences in comparison to iGCT in other sites.[60]
Table 1: Cases of bifocal intracranial germ cell tumors

Click here to view


The concept of synchronous primaries is established and current treatment strategies are based on this. However, it is difficult to be definite that bifocal disease represents synchronous primaries rather than metastatic spread in all cases. A diagnosis of synchronous tumors is supported by their behavior, as data shows the equivalent outcome in bifocal compared to localized germinoma and successful treatment with WVI if there is no other metastasis.[58],[61],[62] A treatment regimen similar to that of localized disease is therefore standard practice. However, it is feasible that some of these patients present with metastatic disease, from suprasellar to pineal or visa versa, given the route of metastasis of iGCT is mostly ventricular. The true disease evolution is unknown, and reports have demonstrated cases of initially localized tumors that subsequently develop a “bifocal” component.[60] Bifocal disease also often presents with endocrine deficiencies, suggesting a primary role for the suprasellar element.[57] The higher rate of metastasis (30%–50% in bifocal disease compared to 15%–20% in nonbifocal disease) and radiologically detectable ventricular deposits in bifocal disease also supports the spread of disease.[60],[62] Some may question whether outcomes of bifocal disease are equivalent and one study of bifocal germinoma found an inferior survival rate (70% of 5-year OS in bifocal germinoma vs. 91%–93% in germinoma in other sites).[60] The authors hypothesized this difference was due to a failure to identify and adequately treat metastatic disease. Alternatively, this could represent different biology in bifocal disease, requiring more aggressive treatment. It could also represent a failure to identify NGGCT elements resulting from either a lack of biopsy or sampling error.

Bifocal NGGCT is rarely described and therefore the outcome is more uncertain. Few reports have provided separate data on germinomatous and NGGCT disease and treatment protocols vary with small numbers and treatment details missing [Table 2]. Most published cases received CSI.[63] However, the recently published SIOP CNS GCT 96 trials showed bifocal NCCGT can be treated as localized disease with focal radiation, resulting in equivalent outcomes. Full details on the bifocal patients in this study are not available.[49] Interestingly in this data, subsequent relapse was localized.
Table 2: Survival and treatment of bifocal intracranial germ cell tumors

Click here to view


In this case, imaging distinguishes two different iGCT subtypes, supporting true synchronous bifocal disease. MRI showed a heterogeneous suprasellar component, suggestive of an NGGCT, whereas the homogeneous pineal component had characteristics typical of germinoma [Figure 1]. MRS demonstrated two distinct metabolic profiles [Figure 2]. The clinical response to treatment supported the differentiation between the two tumors. The pineal tumor showed a rapid complete response to chemotherapy in keeping with a germinomatous lesion. Conventional teaching dictates treatment is directed at the most malignant GCT element which, in terms of prognosis, is the NGGCT. Whether the different tumor elements act independently or whether each is a different manifestation of the same malignant multipotent cells is not currently known. Despite confidence in the diagnosis of localized disease, relapse occurred. The relapse occurred outside of the radiation field, questioning whether a wider radiation field would have prevented recurrence.[71] Serum markers were raised, implying that relapse was an NGGCT component.

With the increased resolution of imaging techniques, it is likely that bifocal disease will be more readily detected. Actively excluding metastasis on imaging and in CSF will be vital to guide treatments. Some experts even consider contiguity between tumors or ependymal seeding as evidence of dissemination and advocate surgical endoscopy for a more accurate assessment.[63],[72] MRS and functional imaging can be useful in differentiating tumor types to aid diagnosis, particularly if mixed components are suspected, or in guiding surgeons to biopsy the most malignant element.

The challenge of common and rare complications

Rapid teratomatous growth of a germ cell tumor is known as GTS. This rare but well-recognized manifestation affects <10% of patients and is characterized by rapid tumor growth during or after adjuvant therapy. It is commonly seen 3–56 months following the onset of adjuvant therapy.[73] Occurrence during the first cycle of therapy, to the best of our knowledge, has not previously been reported. GTS is more common in NGGCT and in males (ratio 4:1). MRIs have classically shown a multi-cystic, honeycombed appearance, leading to some suggesting a pathogenesis related to cystic expansion within existing teratomatous tissue, rather than tumor proliferation.[74] The only proven effective treatment is radical excision. A high index of suspicion and prompt diagnosis may facilitate this by allowing earlier surgical intervention.[75] Recently, more targeted approaches have been considered for GTS. Most expressed the retinoblastoma protein and sustained response to the CDK inhibitor palbociclib has been seen.[77],[78]

Delivery of treatment to iGCT patients presents a considerable clinical challenge. Patients often have multiple comorbidities which complicate chemotherapy administration and complications are common. Hydration fluids are problematic because of DI. Prolonged hospitilization is frequently required and treatment-related mortality high. This is often unrelated to DI.[64] Chemotherapy often requires modification due to toxicity, questioning whether, as in this case, adequate drug doses are delivered at sufficient intensity.[79] Data are lacking, both in describing whether outcome relates to treatment modification and in defining the morbidity-related complications.

Disease relapse

As relapsed iGCT patients are few and not well studied, there is no consistent approach to treatment. In general, treatment is individually tailored based on previous therapy and all feasible modalities are used: attempted resection, reinduction chemotherapy, consolidation with HDC or AuSCR, and radiotherapy. Induction regimens use the first-line agents as well as more novel combinations.[40],[80] Favorable response to gemcitabine, paclitaxel, and oxaliplatin is reported in phase II trials.[3],[80],[81] Radiation at relapse, if possible, is considered a fundamental part of treatment. This proves complex as radiation fields from up-front therapy overlap. With modern techniques and experience, the ability to safely re-irradiate patients is feasible, although the survival benefit is not yet known.[80] Five-year survival of relapsed germinoma using CSI and conventional chemotherapy is reported as 55%–78%.[40],[54] Relapsed NGGCT is more challenging, and the outcome is substantially worse, though some are still salvageable. Data suggests the highest chance of cure with HDC + AuSCR. Salvage rates of 33% have been reported with thiotepa-based regimens.[54] This compares favorably to a larger cohort from the SIOP GCT 96 study where only 9% of patients with relapsed NGGCT were salvaged.[40] All survivors received HDC + AuSCR. In this cohort, there were no survivors with an elevated AFP at the time of relapse.[40],[54]

A success story? The consequences of treatment

As in all brain tumor patients, there is a fine line between treatment success and life-shattering morbidity. Most iGCT patients survive, however, the burden of a central tumor location, endocrine deficits, and treatment can be huge. Little is known of the life quality of these patients. Poor performance scores at the end of treatment, primarily related to surgical morbidity, are associated with poor quality of life.[82] Long-term mortality is ten times higher than peers, with the main causes of death being radiation-related stroke and secondary malignancies.[83]

A brighter future

As in all pediatric malignancies, an increasing emphasis is placed on tumor biology, genetics, and genomics. It has been shown that 53% of iGCTs have an identified somatic or germline mutation, many of which are targetable, including KIT/RAS and AKT/mTOR.[84],[85],[86] New targeted agents promise success without conventional late-effects. However, tumor tissue is needed to advance this work, and this is limited by the current approach of marker-based diagnosis. The question lies in whether mandating tissue collection in clinical trials for the hope of new targeted treatments justifies the risk of morbidity from surgery.

Almost paradoxically, others have concentrated efforts into developing new ways to diagnose or risk-stratify patients without the need for surgery. As discussed, functional imaging techniques may aid noninvasive diagnoses. Better assessment of disease may initiate earlier therapy. Positron emission tomography can quantify metabolic activity and may identify viable tumor to guide and tailor further therapy.[87],[88],[89] Short, noncoding areas of RNA, known as micro-RNAs, have been found circulating in the blood or CSF of all germ cell patients. The four identified micro-RNAs can be used to aid diagnosis, although they cannot yet differentiate between germinoma and NGGCT. Their largest impact may come in monitoring patients. MicroRNA presence is a sensitive indicator of disease and detection may signify relapse or refractory disease much earlier than conventional tumor markers, allowing for earlier intervention.

In the future, patients may have a diagnosis of germinoma, or NGGCT made without a biopsy, due to a combination of conventional imaging, functional imaging, tumor markers, and microRNAs.[57],[89] New classifications may emerge combining this information with histology and tumor molecular markers. An improved understanding of tumor biology may allow fine-tuning of stratification and new targeted agents may ease the burden of therapy. More astute monitoring may detect relapsed disease earlier, improving salvage, and reducing therapy. More work, however, is needed. International collaboration and shared experience must continue in order to resolve optimal treatment approaches. A more complete characterization of bifocal or mixed tumors may help better stratify these patients. More emphasis must be placed on the quality as well as quantity of life and a better description of the complications faced may help to directly manage these.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the parent/legal guardian has given their consent for images and other clinical information to be reported in the journal. The parent/guardian understands that name and initial will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

AP and KM are funded by a National Institute for Health Research Professorship (AP) grant code number 13-0053.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumors of the central nervous system. Acta Neuropathol 2007; 114 (2): 97–109.  Back to cited text no. 1
    
2.
Murray MJ, Bartels U, Nishikawa R, Fangusaro J, Matsutani M, Nicholson JC. Consensus on the management of intracranial germ-cell tumors. Lancet Oncol 2015; 16 (9): e470–7.  Back to cited text no. 2
    
3.
Bokemeyer C, Oechsle K, Honecker F, Mayer F, Hartmann JT, Waller CF, Böhlke I, Kollmannsberger C; German Testicular Cancer Study Group. Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group. Ann Oncol 2008; 19 (3): 448–53.  Back to cited text no. 3
    
4.
McCarthy BJ, Shibui S, Kayama T, Miyaoka E, Narita Y, Murakami M, Matsuda A, Matsuda T, Sobue T, Palis BE, Dolecek TA, Kruchko C, Engelhard HH, Villano JL. Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries. Neuro Oncol 2012; 14 (9): 1194–200.  Back to cited text no. 4
    
5.
Matsutani M, Ushio Y, Abe H, Yamashita J, Shibui S, Fujimaki T, Takakura K, Nomura K, Tanaka R, Fukui M, Yoshimoto T, Hayakawa T, Nagashima T, Kurisu K, Kayama T; Japanese Pediatric Brain Tumor Study Group. Combined chemotherapy and radiation therapy for central nervous system germ cell tumors: preliminary results of a phase II study of the Japanese Pediatric Brain Tumor Study Group. Neurosurg Focus 1998; 5 (1): e7.  Back to cited text no. 5
    
6.
Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol 2012; 14 (Suppl 5): v1–49.  Back to cited text no. 6
    
7.
Makino K, Nakamura H, Yano S, Kuratsu J; Kumamoto Brain Tumor Group. Population-based epidemiological study of primary intracranial tumors in childhood. Childs Nerv Syst 2010; 26 (8): 1029–34.  Back to cited text no. 7
    
8.
Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N, Seto T. Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 1997; 86 (3): 446–55.  Back to cited text no. 8
    
9.
Makino K, Nakamura H, Yano S, Kuratsu J; Kumamoto Brain Tumor Research Group. Incidence of primary central nervous system germ cell tumors in childhood: a regional survey in Kumamoto prefecture in Southern Japan. Pediatr Neurosurg 2013; 49 (3): 155–8.  Back to cited text no. 9
    
10.
Calaminus G, Kortmann R, Worch J, Nicholson JC, Alapetite C, Garrè ML, Patte C, Ricardi U, Saran F, Frappaz D. 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 Oncol 2013; 15 (6): 788–96.  Back to cited text no. 10
    
11.
Bouffet E, Baranzelli MC, Patte C, Portas M, Edan C, Chastagner P, Mechinaud-Lacroix F, Kalifa C. Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience. Société Française d'Oncologie Pédiatrique. Br J Cancer 1999; 79 (7–8): 1199–204.  Back to cited text no. 11
    
12.
Wong LC, Yang TL, Gao F, Tan AM, Sethi VK, Chua EJ. Intracranial germ cell tumour: experience of a Singaporean institution over 11-year period. Singapore Med J 2002; 43 (4): 182–8.  Back to cited text no. 12
    
13.
Liang L, Korogi Y, Sugahara T, Ikushima I, Shigematsu Y, Okuda T, Takahashi M, Kochi M, Ushio Y. MRI of intracranial germ-cell tumors. Neuroradiology 2002; 44 (5): 382–8.  Back to cited text no. 13
    
14.
Awa R, Campos F, Arita K, Sugiyama K, Tominaga A, Kurisu K, Yamasaki F, Karki P, Tokimura H, Fukukura Y, Fujii Y, Hanaya R, Oyoshi T, Hirano H. Neuroimaging diagnosis of pineal region tumors – Quest for pathognomonic finding of germinoma. Neuroradiology 2014; 56 (7): 525–34.  Back to cited text no. 14
    
15.
Jorsal T, Rørth M. Intracranial germ cell tumors. A review with special reference to endocrine manifestations. Acta Oncol 2012; 51 (1): 3–9.  Back to cited text no. 15
    
16.
Ogawa K, Shikama N, Toita T, Nakamura K, Uno T, Onishi H, Itami J, Kakinohana Y, Kinjo T, Yoshii Y, Ito H, Murayama S. Long-term results of radiotherapy for intracranial germinoma: a multi-institutional retrospective review of 126 patients. Int J Radiat Oncol Biol Phys 2004; 58 (3): 705–13.  Back to cited text no. 16
    
17.
Kumanogoh A, Kasayama S, Kouhara H, Koga M, Arita N, Hayakawa T, Kishimoto T, Sato B. Effects of therapy on anterior pituitary functions in patients with primary intracranial germ cell tumor. Endocr J 1994; 41 (3): 287–92.  Back to cited text no. 17
    
18.
Phi JH, Kim SK, Lee YA, Shin CH, Cheon JE, Kim IO, Yang SW, Wang KC. Latency of intracranial germ cell tumors and diagnosis delay. Childs Nerv Syst 2013; 29 (10): 1871–81.  Back to cited text no. 18
    
19.
Frappaz D, Pedone C, Thiesse P, Szathmari A, Conter CF, Mottolese C, Carrie C. Visual complaints in intracranial germinomas. Pediatr Blood Cancer 2017; 64 (10): e26543.  Back to cited text no. 19
    
20.
Malbari F, Gershon TR, Garvin JH, Allen JC, Khakoo Y, Levy AS, Dunkel IJ. Psychiatric manifestations as initial presentation for pediatric CNS germ cell tumors, a case series. Childs Nerv Syst 2016; 32 (8): 1359–62.  Back to cited text no. 20
    
21.
Domínguez-Pinilla N, Martínez de Aragón A, Diéguez Tapias S, Toldos O, Hinojosa Bernal J, Rigal Andrés M, González-Granado LI. Evaluating the apparent diffusion coefficient in MRI studies as a means of determining paediatric brain tumour stages. Neurologia 2016; 31 (7): 459–65.  Back to cited text no. 21
    
22.
Humphries PD, Sebire NJ, Siegel MJ, Olsen ØE. Tumors in pediatric patients at diffusion-weighted MR imaging: apparent diffusion coefficient and tumor cellularity. Radiology 2007; 245 (3): 848–54.  Back to cited text no. 22
    
23.
Kralik SF, Taha A, Kamer AP, Cardinal JS, Seltman TA, Ho CY. Diffusion imaging for tumor grading of supratentorial brain tumors in the first year of life. Am J Neuroradiol 2014; 35 (4): 815–23.  Back to cited text no. 23
    
24.
Yamashita Y, Kumabe T, Higano S, Watanabe M, Tominaga T. Minimum apparent diffusion coefficient is significantly correlated with cellularity in medulloblastomas. Neurol Res 2009; 31 (9): 940–6.  Back to cited text no. 24
    
25.
Douglas-Akinwande AC, Ying J, Momin Z, Mourad A, Hattab EM. Diffusion-weighted imaging characteristics of primary central nervous system germinoma with histopathologic correlation. Acad Radiol 2009; 16 (11): 1356–65.  Back to cited text no. 25
    
26.
Ogiwara H, Tsutsumi Y, Matsuoka K, Kiyotani C, Terashima K, Morota N. Apparent diffusion coefficient of intracranial germ cell tumors. J Neurooncol 2015; 121 (3): 565–71.  Back to cited text no. 26
    
27.
Peet AC, Arvanitis TN, Auer DP, Davies NP, Hargrave D, Howe FA, Jaspan T, Leach MO, Macarthur D, MacPherson L, Morgan PS, Natarajan K, Payne GS, Saunders D, Grundy RG; CCLG Functional Imaging Group. The value of magnetic resonance spectroscopy in tumour imaging. Arch Dis Child 2008; 93 (9): 725–7.  Back to cited text no. 27
    
28.
Harris LM, Davies NP, Wilson S, MacPherson L, Natarajan K, English MW, Brundler MA, Arvanitis TN, Grundy RG, Peet AC. Short echo time single voxel 1H magnetic resonance spectroscopy in the diagnosis and characterisation of pineal tumors in children. Pediatr Blood Cancer 2011; 57 (6): 972–7.  Back to cited text no. 28
    
29.
Borja MJ, Plaza MJ, Altman N, Saigal G. Conventional and advanced MRI features of pediatric intracranial tumors: supratentorial tumors. Am J Roentgenol 2013; 200 (5): W483–503.  Back to cited text no. 29
    
30.
Sawamura Y, de Tribolet N, Ishii N, Abe H. Management of primary intracranial germinomas: diagnostic surgery or radical resection? J Neurosurg 1997; 87 (2): 262–6.  Back to cited text no. 30
    
31.
Nishizaki T, Kajiwara K, Adachi N, Tsuha M, Nakayama H, Ohshita N, Ikeda N, Ito H, Suzuki M. Detection of craniospinal dissemination of intracranial germ cell tumors based on serum and cerebrospinal fluid levels of tumour markers. J Clin Neurosci 2001; 8 (1): 27–30.  Back to cited text no. 31
    
32.
Echevarría ME, Fangusaro J, Goldman S. Pediatric central nervous system germ cell tumors: a review. Oncologist 2008; 13 (6): 690–9.  Back to cited text no. 32
    
33.
Robertson PL, DaRosso RC, Allen JC. Improved prognosis of intracranial non-germinoma germ cell tumors with multimodality therapy. J Neurooncol 1997; 32 (1): 71–80.  Back to cited text no. 33
    
34.
Ogino H, Shibamoto Y, Takanaka T, Suzuki K, Ishihara S, Yamada T, Sugie C, Nomoto Y, Mimura M. CNS germinoma with elevated serum human chorionic gonadotropin level: clinical characteristics and treatment outcome. Int J Radiat Oncol 2005; 62 (3): 803–8.  Back to cited text no. 34
    
35.
Carlos Chung KH, Owler BK, Dexter M, Chaseling R. Paediatric germ cell tumors of the central nervous system: results and experience from a tertiary-referral paediatric institution in Australia. J Clin Neurosci 2013; 20 (4): 514–9.  Back to cited text no. 35
    
36.
Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, Finlay JL. Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. J Clin Oncol 2004; 22 (5): 846–53.  Back to cited text no. 36
    
37.
Balmaceda C, Heller G, Rosenblum M, Diez B, Villablanca JG, Kellie S, Maher P, Vlamis V, Walker RW, Leibel S, Finlay JL. 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 (11): 2908–15.  Back to cited text no. 37
    
38.
Khatua S, Dhall G, O'Neil S, Jubran R, Villablanca JG, Marachelian A, Nastia A, Lavey R, Olch AJ, Gonzalez I, Gilles F, Nelson M, Panigrahy A, McComb G, Krieger M, Fan J, Sposto R, Finlay JL. Treatment of primary CNS germinomatous germ cell tumors with chemotherapy prior to reduced dose whole ventricular and local boost irradiation. Pediatr Blood Cancer 2010; 55 (1): 42–6.  Back to cited text no. 38
    
39.
Kim JW, Kim WC, Cho JH, Kim DS, Shim KW, Lyu CJ, Won SC, Suh CO. A multimodal approach including craniospinal irradiation improves the treatment outcome of high-risk intracranial nongerminomatous germ cell tumors. Int J Radiat Oncol Biol Phys 2012; 84 (3): 625–31.  Back to cited text no. 39
    
40.
Murray MJ, Bailey S, Heinemann K, Mann J, Göbel UK, Saran F, Hale JP, Calaminus G, Nicholson JC. Treatment and outcomes of UK and German patients with relapsed intracranial germ cell tumors following uniform first-line therapy: relapsed intracranial germ cell tumors. Int J Cancer 2017; 141 (3): 621–35.  Back to cited text no. 40
    
41.
da Silva NS, Cappellano AM, Diez B, Cavalheiro S, Gardner S, Wisoff J, Kellie S, Parker R, Garvin J, Finlay J. Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study. Pediatr Blood Cancer 2010; 54 (3): 377–83.  Back to cited text no. 41
    
42.
Kakkar A, Biswas A, Kalyani N, Chatterjee U, Suri V, Sharma MC, Goyal N, Sharma BS, Mallick S, Julka PK, Chinnaswamy G, Arora B, Sridhar E, Chatterjee S, Jalali R, Sarkar C. Intracranial germ cell tumors: a multi-institutional experience from three tertiary care centers in India. Childs Nerv Syst 2016; 32 (11): 2173–80.  Back to cited text no. 42
    
43.
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.  Back to cited text no. 43
    
44.
Ogiwara H, Kiyotani C, Terashima K, Morota N. Second-look surgery for intracranial germ cell tumors. Neurosurgery 2015; 76 (6): 658–62.  Back to cited text no. 44
    
45.
Kanamori M, Kumabe T, Saito R, Yamashita Y, Sonoda Y, Ariga H, Takai Y, Tominaga T. Optimal treatment strategy for intracranial germ cell tumors: a single institution analysis. J Neurosurg Pediatr 2009; 4 (6): 506–14.  Back to cited text no. 45
    
46.
Haas-Kogan DA, Missett BT, Wara WM, Donaldson SS, Lamborn KR, Prados MD, Fisher PG, Huhn SL, Fisch BM, Berger MS, Le QT. Radiation therapy for intracranial germ cell tumors. Int J Radiat Oncol Biol Phys 2003; 56 (2): 511–8.  Back to cited text no. 46
    
47.
Alapetite C, Brisse H, Patte C, Raquin MA, Gaboriaud G, Carrie C, Habrand JL, Thiesse P, Cuilliere JC, Bernier V, Ben-Hassel M, Frappaz D, Baranzelli MC, Bouffet E. Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience. Neuro Oncol 2010; 12 (12): 1318–25.  Back to cited text no. 47
    
48.
Calaminus G, Frappaz D, Kortmann RD, Krefeld B, Saran F, Pietsch T, Vasiljevic A, Garre ML, Ricardi U, Mann JR, Göbel U, Alapetite C, Murray MJ, Nicholson JC. Outcome of patients with intracranial non-germinomatous germ cell tumors-Lessons from the SIOP-CNS-GCT-96 trial. Neuro Oncol 2017; 19 (12): 1661–72.  Back to cited text no. 48
    
49.
Kretschmar C, Kleinberg L, Greenberg M, Burger P, Holmes E, Wharam M. 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 2007; 48 (3): 285–91.  Back to cited text no. 49
    
50.
De B, Cahlon O, Dunkel IJ, De Braganca KC, Khakoo Y, Gilheeney SW, Souweidane MM, Wolden SL. Reduced-volume radiotherapy for patients with localized intracranial nongerminoma germ cell tumors. J Neurooncol 2017; 134 (2): 349–56.  Back to cited text no. 50
    
51.
Fu H, Guo X, Li R, Xing B. Radiotherapy and chemotherapy plus radiation in the treatment of patients with pure intracranial germinoma: a meta-analysis. J Clin Neurosci 2017; 43: 32–8.  Back to cited text no. 51
    
52.
Baek HJ, Park HJ, Sung KW, Lee SH, Han JW, Koh KN, Im HJ, Kang HJ, Park KD. 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 2013; 114 (3): 329–38.  Back to cited text no. 52
    
53.
Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC, Halpern S, Finlay JL. Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. J Clin Oncol 2004; 22 (10): 1934–43.  Back to cited text no. 53
    
54.
Bouffet E. The role of myeloablative chemotherapy with autologous hematopoietic cell rescue in central nervous system germ cell tumors. Pediatr Blood Cancer 2010; 54 (4): 644–6.  Back to cited text no. 54
    
55.
Swischuk LE, Bryan RN. Double midline intracranial atypical teratomas: a recognizable neuroendocrinologic syndrome. Am J Roentgenol Radium Ther Nucl Med 1974; 122 (3): 517–24.  Back to cited text no. 55
    
56.
Aizer AA, Sethi RV, Hedley-Whyte ET, Ebb D, Tarbell NJ, Yock TI, Macdonald SM. Bifocal intracranial tumors of nongerminomatous germ cell etiology: diagnostic and therapeutic implications. Neuro Oncol 2013; 15 (7): 955–60.  Back to cited text no. 56
    
57.
Al-Mahfoudh R, Zakaria R, Irvine E, Pizer B, Mallucci CL. The management of bifocal intracranial germinoma in children. Childs Nerv Syst 2014; 30 (4): 625–30.  Back to cited text no. 57
    
58.
Phuakpet K, Larouche V, Hawkins C, Huang A, Tabori U, Bartels UK, Bouffet E. Rare presentation of supratentorial primitive neuroectodermal tumors mimicking bifocal germ cell tumors: 2 case reports. J Pediatr Hematol Oncol 2016; 38 (2): e67–70.  Back to cited text no. 58
    
59.
Phi JH, Kim SK, Lee J, Park CK, Kim IH, Ahn HS, Shin HY, Kim IO, Jung HW, Kim DG, Paek SH, Wang KC. The enigma of bifocal germ cell tumors in the suprasellar and pineal regions: synchronous lesions or metastasis? J Neurosurg Pediatr 2013; 11 (2): 107–14.  Back to cited text no. 59
    
60.
Lafay-Cousin L, Millar BA, Mabbott D, Spiegler B, Drake J, Bartels U, Huang A, Bouffet E. Limited-field radiation for bifocal germinoma. Int J Radiat Oncol Biol Phys 2006; 65 (2): 486–92.  Back to cited text no. 60
    
61.
Weksberg DC, Shibamoto Y, Paulino AC. Bifocal intracranial germinoma: a retrospective analysis of treatment outcomes in 20 patients and review of the literature. Int J Radiat Oncol Biol Phys 2012; 82 (4): 1341–51.  Back to cited text no. 61
    
62.
Cuccia V, Alderete D. Suprasellar/pineal bifocal germ cell tumors. Childs Nerv Syst 2010; 26 (8): 1043–9.  Back to cited text no. 62
    
63.
Breen WG, Blanchard MJ, Rao AN, Daniels DJ, Buckner JC, Laack NN. Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell tumors: long-term institutional experience with chemotherapy, surgery, and dose- and field-adapted radiotherapy. Pediatr Blood Cancer 2017; 64 (11): e26637.  Back to cited text no. 63
    
64.
Afzal S, Wherrett D, Bartels U, Tabori U, Huang A, Stephens D, Bouffet E. Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy. J Neurooncol 2010; 97 (3): 393–9.  Back to cited text no. 64
    
65.
Baranzelli MC, Patte C, Bouffet E, Couanet D, Habrand JL, Portas M, Lejars O, Lutz P, Le Gall E, Kalifa C. Nonmetastatic intracranial germinoma: the experience of t66he French society of pediatric oncology. Cancer 1997; 80 (9): 1792–7.  Back to cited text no. 65
    
66.
Wu CC, Guo WY, Chang FC, Luo CB, Lee HJ, Chen YW, Lee YY, Wong TT. MRI features of pediatric intracranial germ cell tumor subtypes. J Neurooncol 2017; 134 (1): 221–30.  Back to cited text no. 66
    
67.
Odagiri K, Omura M, Hata M, Aida N, Niwa T, Ogino I, Kigasawa H, Ito S, Adachi M, Inoue T. Treatment outcomes, growth height, and neuroendocrine functions in patients with intracranial germ cell tumors treated with chemoradiation therapy. Int J Radiat Oncol Biol Phys 2012; 84 (3): 632–8.  Back to cited text no. 67
    
68.
Cheng S, Kilday JP, Laperriere N, Janzen L, Drake J, Bouffet E, Bartels U. Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation. J Neurooncol 2016; 127 (1): 173–80.  Back to cited text no. 68
    
69.
Van Battum P, Huijberts MS, Heijckmann AC, Wilmink JT, Nieuwenhuijzen Kruseman AC. Intracranial multiple midline germinomas: is histological verification crucial for therapy. Neth J Med 2007; 65 (10): 386–9.  Back to cited text no. 69
    
70.
Duron L, Sadones F, Thiesse P, Cellier C, Alapetite C, Doz F, Frappaz D, Brisse HJ. Loco-regional extensions of central nervous system germ cell tumors: a retrospective radiological analysis of 100 patients. Neuroradiology 2018; 60 (1): 27–34.  Back to cited text no. 70
    
71.
Reddy AT, Wellons JC 3rd, Allen JC, Fiveash JB, Abdullatif H, Braune KW, Grabb PA. Refining the staging evaluation of pineal region germinoma using neuroendoscopy and the presence of preoperative diabetes insipidus. Neuro Oncol 2004; 6 (2): 127–33.  Back to cited text no. 71
    
72.
Khoo B, Ramakonar HH, Robbins P, Honeybul S. Intracranial monodermal teratoma presenting with growing teratoma syndrome. J Surg Case Rep 2017; 2017 (5):rjx038.  Back to cited text no. 72
    
73.
Oya S, Saito A, Okano A, Arai E, Yanai K, Matsui T. The pathogenesis of intracranial growing teratoma syndrome: proliferation of tumor cells or formation of multiple expanding cysts? Two case reports and review of the literature. Childs Nerv Syst 2014; 30 (8): 1455–61.  Back to cited text no. 73
    
74.
Kim CY, Choi JW, Lee JY, Kim SK, Wang KC, Park SH, Choe G, Ahn HS, Kim IH, Cho BK. Intracranial growing teratoma syndrome: clinical characteristics and treatment strategy. J Neurooncol 2011; 101 (1): 109–15.  Back to cited text no. 74
    
75.
Schultz KA, Petronio J, Bendel A, Patterson R, Vaughn DJ. PD0332991 (Palbociclib) for treatment of pediatric intracranial growing teratoma syndrome: palbociclib for intracranial growing teratoma. Pediatr Blood Cancer 2015; 62 (6): 1072–4.  Back to cited text no. 75
    
76.
Vaughn DJ, Hwang WT, Lal P, Rosen MA, Gallagher M, O'Dwyer PJ. Phase 2 trial of the cyclin-dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein-expressing germ cell tumors: phase 2 trial of palbociclib for GCT. Cancer 2015; 121 (9): 1463–8.  Back to cited text no. 76
    
77.
Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, Finlay JL. 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.  Back to cited text no. 77
    
78.
Wong K, Opimo AB, Olch AJ, All S, Waxer JF, Clark D, Cheng J, Chlebik A, Erdreich-Epstein A, Krieger MD, Tamrazi B, Dhall G, Finlay JL, Chang EL. Re-irradiation of recurrent pineal germ cell tumors with radiosurgery: report of two cases and review of literature. Cureus 2016; 8 (4): e585.  Back to cited text no. 78
    
79.
Finlay JL, Liu Y, Haley K, Erdreich-Epstein A, Rushing T, Grimm J, Wong KE, Kiehna E, Krieger M D, Gilles F, Badie B, D'Apuzzo M, Dhall G. Preliminary results of a prospective feasibility pilot study of “gempox” (gemcitabine, oxaliplatin, and paclitaxel) in pediatric and adult patients with refractory or recurrent central nervous system (CNS) germ cell tumors (GCT): the international CNS GCT consortium trial, CNS GCT-4. Neuro Oncol 2014; 16 (Suppl 3): iii26.  Back to cited text no. 79
    
80.
Jinguji S, Yoshimura J, Nishiyama K, Aoki H, Nagasaki K, Natsumeda M, Yoneoka Y, Fukuda M, Fujii Y. Factors affecting functional outcomes in long-term survivors of intracranial germinomas: a 20-year experience in a single institution. J Neurosurg Pediatr 2013; 11 (4): 454–63.  Back to cited text no. 80
    
81.
Acharya S, DeWees T, Shinohara ET, Perkins SM. Long-term outcomes and late effects for childhood and young adulthood intracranial germinomas. Neuro Oncol 2015; 17 (5): 741–6.  Back to cited text no. 81
    
82.
Gao YP, Jiang JY, Liu Q. Expression and mutation of c-Kit in intracranial germ cell tumors: a single-centre retrospective study of 30 cases in China. Oncol Lett 2016; 11 (5): 2971–6.  Back to cited text no. 82
    
83.
Lindsay H, Huang Y, Du Y, Braun FK, Teo WY, Kogiso M, Qi L, Zhang H, Zhao S, Mao H, Lin F, Baxter P, Su JM, Terashima K, Perlaky L, Chintagumpala M, Adesina A, Lau CC, Williams Parsons D, Li XN. Preservation of KIT genotype in a novel pair of patient-derived orthotopic xenograft mouse models of metastatic pediatric CNS germinoma. J Neurooncol 2016; 128 (1): 47–56.  Back to cited text no. 83
    
84.
Fukushima S, Otsuka A, Suzuki T, Yanagisawa T, Mishima K, Mukasa A, Saito N, Kumabe T, Kanamori M, Tominaga T, Narita Y, Shibui S, Kato M, Shibata T, Matsutani M, Nishikawa R, Ichimura K; Intracranial Germ Cell Tumor Genome Analysis Consortium (iGCT Consortium). 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.  Back to cited text no. 84
    
85.
Tsouana E, Stoneham S, Fersht N, Kitchen N, Gaze M, Bomanji J, Fraioli F, Hargrave D, Shankar A. Evaluation of treatment response using integrated 18F-labeled choline positron emission tomography/magnetic resonance imaging in adolescents with intracranial non-germinomatous germ cell tumors. Pediatr Blood Cancer 2015; 62 (9): 1661–3.  Back to cited text no. 85
    
86.
Kelly PA, Metcalfe K, Evanson J, Sabin I, Plowman PN, Monson JP. Positron emission tomography in the diagnosis and management of intracranial germ cell tumors. Horm Res 2009; 72 (3): 190–6.  Back to cited text no. 86
    
87.
Fukuoka K, Yanagisawa T, Watanabe Y, Suzuki T, Matsutani M, Kuji I, Nishikawa R. Clinical interpretation of residual uptake in 11C-methionine positron emission tomography after treatment of basal ganglia germ cell tumors: report of 3 cases. J Neurosurg Pediatr 2015; 16 (4): 367–71.  Back to cited text no. 87
    
88.
Murray MJ, Bell E, Raby KL, Rijlaarsdam MA, Gillis AJ, Looijenga LH, Brown H, Destenaves B, Nicholson JC, Coleman N. A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumors. Br J Cancer 2016; 114 (2): 151–62.  Back to cited text no. 88
    
89.
Murray MJ, Halsall DJ, Hook CE, Williams DM, Nicholson JC, Coleman N. Identification of MicroRNAs from the miR-371 ∼ 373 and miR-302 clusters as potential serum biomarkers of malignant germ cell tumors. Am J Clin Pathol 2011; 135 (1): 119–25.  Back to cited text no. 89
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case Report
Discussion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed133    
    Printed13    
    Emailed0    
    PDF Downloaded27    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]