Pediatric Germ Cell Tumors Research Articles

GCT-77 - Burden of late effects and challenges faced in the long-term follow-up of paediatric germ cell tumour survivors: A report from India

GCT-77 - Burden of late effects and challenges faced in the long-term follow-up of paediatric germ cell tumour survivors: A report from India

Outcome of children with malignant germ cell tumors by response status at the end of induction chemotherapy.

10023 Background: The management of pediatric malignant germ cell tumors (MGCTs) includes induction therapy with 3-4 cycles cisplatin, etoposide, bleomycin (PEb). The current practice recommends 2-3 cycles of PEb (total 6 cycles) as consolidation therapy if response is not complete at the end of induction, a significantly different approach than that used in adult patients who receive a standard number of cycles. Furthermore, there is no evidence supporting the addition of a consolidation phase with PEb in pediatric patients with MGCTs. Methods: We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs (AGCT0132). All patients received 3 cycles of PEb and underwent response assessment at the end of induction. Complete Response (CR) was defined as negative tumor markers and no viable residual lesion. Patients in CR were not to receive any further chemotherapy. Patients not in CR were prescribed 3 additional cycles of PEb as consolidation. Event-free survival (EFS) and Overall survival (OS) was calculated using the Kaplan-Meier method. Results: Among 210 patients enrolled, 193 patients had CR after 3 cycles of induction chemotherapy, and their post-induction 4yr-EFS and OS was 93% and 99%. Fifteen patients were not in CR at the end of the first 3 cycles and received additional chemotherapy, and their 4yr-EFS and OS was 51% and 60%. Conclusions: Children with MGCTs who have a partial response after the first 3 cycles of chemotherapy had an inferior outcome compared to those with a CR, despite receiving additional cycles of PEb chemotherapy. Thus, we conclude that consolidation is of unclear benefit. Although our results are limited by small sample size and lack of comparator, we propose that pediatric MGCT patients who fail to achieve a CR after standard induction chemotherapy should receive a salvage regimen with different agents rather than consolidation with more cycles of the same chemotherapy.

Chromosomal gains of 12p and 1q are not associated with inferior outcome of pediatric and adolescent germ cell tumors.

Pediatric germ cell tumors (GCT) are rare and very heterogeneous neoplasms that show a high diversity in tumor biology and histology. The clinical behavior cannot be predicted based on morphology or immunohistochemistry. The aim of this study was to investigate a large number of pediatric GCT regarding chromosomal gains of 12p and 1q. One hundred and eighty pediatric nonseminomatous GCT, that is, mature teratomas, immature teratomas, yolk sac tumors, and mixed germ cell tumors, from three age groups were evaluated for 1q and 12p gains by fluorescence in situ hybridization in tissue micro arrays. The results were correlated with tumor biology and clinical data. Eleven out of 143 GCT showed gains of 1q. In 29/157 GCT a gain of 12p was found. Prepubertal patients (≤6 years of age) more often displayed gains of 1q compared to pubertal/adolescent patients (11-17 years of age), whereas pubertal/adolescent patients showed gains of 12p most frequently. Twenty-one out of 155 patients suffered from relapse or metachronous disease. Patients with and without gains of 1q or 12p did not differ in frequency of these events. However, the likelihood of occurrence of these clinical events varied depending on the histological type of the tumor. The biological behavior of pediatric GCT depends more on the histological type of the tumor than on the genetic aberrations examined in this study. Gains of 1q and 12p are not suitable to predict the clinical outcome of GCT in childhood. Nevertheless, both genetic alterations might be used as biomarkers to distinguish different histological types of GCT and therefore could be of diagnostic value, especially in borderline cases.

Hedgehog signalling network gene status analysis in paediatric intracranial germ cell tumours.

Germ cell tumours (GCTs) in the children comprise a group of tumours that originate from primordial germ cells but their pathogenesis is not clear. Intracranial GCTs represent a special subset of these paediatric neoplasms. Hedgehog (Hh) pathway gene status in GCTs is generally unexplored, while Hh signalling is involved in germ cell biology. Comparative genomic profiling analysis with a microarray-comparative genomic hybridization (CGH) + single nucleotide polymorphism (SNP) technique in a group of intracranial paediatric GCTs was performed. The analysis included evaluation of genes being ligands, receptors, regulators, effectors, and targets of Hh signalling. Chromosomal aberrations were found in 62% of examined tumours, showing their heterogeneity. A number of private genomic imbalances were observed, but only a few recurrent ones. The most common numerical changes were trisomies 19, 21 and monosomies 13, 18 while the most frequent structural aberration was gain/amplification of the chromosome 12p. The analysis of the gene status of Hh network elements showed imbalances in a proportion of tumours. PTCH1, GLI2, IHH and ZIC2 gene aberrations occurred most frequently. Moreover, six tumours had various copy gains or losses of several other genes involved in the pathway, including HHIP, GLI1, GLI3, DHH, SHH, SMO, PTCH2, and several genes from the WNT group. Interestingly, four cases showed losses of pathway repressors, with parallel gains of activators in two of them. Correlations with patho-clinical tumour features were not found, most probably due to the heterogeneity of the examined limited group. Our results show few genomic alterations related to the Hh signalling pathway genes in paediatric intracranial GCTs. Further analysis of Hedgehog pathway alterations can potentially disclose its biological significance and define new prognostic factors and/or therapeutic targets for high-risk patients.

Differences in DNA methylation profiles by histologic subtype of paediatric germ cell tumours: a report from the Children\u2019s Oncology Group

BackgroundAbnormal DNA methylation may be important in germ cell tumour (GCT) aetiology, as germ cells undergo complete epigenetic reprogramming during development. GCTs show differences in global and promoter methylation patterns by histologic subtype. We conducted an epigenome-wide study to identify methylation differences by GCT histology.MethodsUsing the Illumina HumanMethylation450K array we measured methylation in 154 paediatric GCTs (21 germinomas/seminomas/dysgerminoma, 70 yolk sac tumours [YST], 9 teratomas, and 54 mixed histology tumours). We identified differentially methylated regions (DMRs) between GCT histologies by comparing methylation beta values.ResultsWe identified 8,481 DMRs (FWER < 0.05). Unsupervised hierarchical clustering of individual probes within DMRs resulted in four high level clusters closely corresponding to tumour histology. Clusters corresponding to age, location, sex and FFPE status were not observed within these DMRs. Germinomas displayed lower levels of methylation across the DMRs relative to the other histologic subtypes. Pathway analysis on the top 10% of genes with differential methylation in germinomas/seminomas/dysgerminoma compared to YST suggested angiogenesis and immune cell-related pathways displayed decreased methylation in germinomas/seminomas/dysgerminoma relative to YST.ConclusionsPaediatric GCT histologies have differential methylation patterns. The genes that are differentially methylated may provide insights into GCT aetiology including the timing of GCT initiation.

Abstract A25: Prevalence of Klinefelter syndrome among males aged 0-19 years diagnosed with germ cell tumors: A report from the Children’s Oncology Group

Abstract Previous studies have suggested that males with Klinefelter syndrome (KS; 47, XXY) may be more likely to develop germ cell tumors (GCTs), particularly mediastinal GCTs. Due to the rarity of pediatric GCTs, there are no reports characterizing the prevalence of KS among males diagnosed with GCTs. We used data from a Children’s Oncology Group epidemiology study (2008-2015) to evaluate the prevalence of KS in males (n=433) diagnosed with GCTs (aged 0-19 years). These 433 cases provided saliva samples and had one parent who was willing to participate in the study and complete a questionnaire including questions about health history, demographics, and environmental exposures. Tumor characteristics (location and histology) were abstracted from pathology reports provided by the treating institution. GCT cases were classified as having KS if they had evidence of an extra copy of the X chromosome based on evaluation of array data from Illumina HumanCoreExome-12 genotyping chips. Genvisis was used to identify samples with sex aneuploidy and to determine the parent-of-origin for the nondisjunction. Using chi-square tests, we examined differences in age at diagnosis, race/ethnicity, tumor location and histology, and a number of birth characteristics between KS-GCT cases and GCT cases without chromosomal abnormalities (n=415). Using publically available data, we estimated the 1-year risk and corresponding Risk Ratio (RR) and 95% Confidence Interval (95% CI) of a male with KS developing a GCT. Based on analysis of array genotyping data, 3% (n=13) of male GCT cases had KS. Among these 13 cases, the extra X chromosome was of maternal origin in 7 cases and of paternal origin in 6 cases. Of the 13 KS cases with genotyping data, 5/9 (56%) KS-GCT cases with parental questionnaire data reported receiving a diagnosis of KS. The average age at GCT diagnosis for cases with genotyping-detected KS (n=13) was 13.8 years (standard deviation [SD], 4.4 years) compared with 12.5 years (SD, 6.2 years) for GCT cases without chromosomal abnormalities (n=415; p=0.45). We did not observe significant differences in patient or birth characteristics including race, birth weight and length, maternal age, paternal age, and the use of fertility drugs between the two groups. We confirmed that KS-GCT cases were significantly more likely to be diagnosed with extragonadal tumors (GCT [n=69/411; 17%]; KS-GCT [n=11/13; 85%]; p&amp;lt;0.01), particularly mediastinal tumors (GCT [n=20/406; 5%]; KS-GCT [9/13; 69%]; p&amp;lt;0.01), than GCT cases without chromosomal abnormalities. Mixed/other histology was the most common histologic subtype for KS-GCT (46%) and GCTs among patients without chromosomal abnormalities (41%; p=0.60). Based on data from the CDC WONDER database and the US Census Bureau, in 2013, the risk of developing a GCT among males aged 0-19 years without KS was estimated to be 0.000014 or approximately 1 in 70,000. Using our estimate that 3% of GCTs in males aged 0-19 years are diagnosed among patients who also have KS, we estimated the risk of a GCT among males with KS to be 0.00025, or approximately 1 in 4,000 (RR: 18.8; 95% CI: 11.7, 30.0). In our large case series of males diagnosed with GCTs, we observed that 3% of GCT cases (n=13/433) were also carriers of an extra X chromosome based on array genotyping data and were thus classified as having KS. Males aged 0-19 years with KS experience a large increase in risk of developing a GCT compared with males from the general population. Collectively, these findings suggest that young males with KS should be monitored for the development of a GCT. Similarly, the possibility of KS should be considered in males diagnosed with a mediastinal GCT during childhood or adolescence and these patients should be tested for the presence of KS. Citation Format: Lindsay A. Williams, Nathan Pankratz, John Lane, Michelle Roesler, Michaela Richardson, A. Lindsay Frazier, James Amatruda, Jenny N. Poynter. Prevalence of Klinefelter syndrome among males aged 0-19 years diagnosed with germ cell tumors: A report from the Children’s Oncology Group [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr A25.

Abstract 2064: Differences in methylation patterns by pediatric germ cell tumor histologic subtype

Abstract Anomalous DNA methylation contributes to carcinogenesis by regulating gene expression and may be important in germ cell tumor (GCT) development as germ cells undergo tremendous epigenetic reprogramming during embryogenesis. Histologic subtypes of GCTs show differences in global methylation patterns with less differentiated tumors (e.g. embryonal carcinoma) experiencing lower levels of global methylation relative to more differentiated tumors (e.g. teratoma). Differences in promoter methylation have also been reported in GCTs. In particular, developmental signaling pathways and the BMP/TGF beta pathway have been consistently found to be differentially methylated. In this analysis, we conducted an epigenome wide association study to identify gene-specific methylation differences by GCT histology. Using the Illumina HumanMethylation450K array we determined methylation profiles for 154 pediatric GCTs (21 germinomas, 54 mixed, 9 teratomas, 70 yolk sac tumors [YST]) from fresh frozen and formalin fixed paraffin embedded tumor tissue samples. Fisher's exact tests were used to assess differences in the distributions of age group, sex, and tumor location by histologic subtype (alpha=0.05 for a two-sided test of significance [SAS v9.4]). Bioconductor package minfi was used to identify differential methylation between GCT histologic subtypes by comparing the methylation beta values. To identify differential methylation of genes predictive of tumor histology, a generalized linear model (glm) with LASSO was fit (R v3.4.1) to the quantile normalized beta values for all probes from all samples. There were significant differences in age, sex, and tumor location by histologic subtype (all p&amp;lt;0.01). We observed unique clusters for both germinoma and YST, but a single cluster for mixed tumors and teratoma. The methylation clusters did not differ by age, sex or FFPE status after accounting for histologic subtype. When stratifying by age group (0-10 vs. 11-19 years), we observed 2,043 differentially methylated regions (DMRs) (FWER &amp;lt;0.05); however, these differences did not persist once we adjusted for tumor histology. Differential methylation tests across histologic subtypes resulted in 8,049 DMRs (FWER &amp;lt; 0.05). Germinoma clustered most consistently and displayed a unique methylation pattern relative to other tumor types, which were more similar to one another. Fitting a glm with LASSO to the methylation data identified 21 probes that were predictive of histologic subtype with misclassification error &amp;lt; 20%: ANKRD24, ASL, ATG13, CCDC53, CKB, FAM224B, FZD10, KCNMB3, LINC00939, LOC101927248, MIR378C, MMP14, MUC1, OGFOD3, PLP2, PLPP3, PRR5, SERPINA6¸ SGSM2, VARS, and YWHAZ. In our analyses, we identified a large number of genes with differential methylation by tumor histology. These data may be informative in understanding GCT etiology and the timing of GCT initiation. Citation Format: Lindsay A. Williams, Lauren Mills, Anthony J. Hooten, Erica Langer, Michelle Roesler, A Lindsay Frazier, James Amatruda, Jenny N. Poynter, Jenny N. Poynter. Differences in methylation patterns by pediatric germ cell tumor histologic subtype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2064.

OVARIAN CARCINOMA IN CHILDREN: A CASE REPORT

Pediatric germ cell tumors (GCTs) are the most important raretumors in childhood and adolescence and are often asymptomatic until theybecome an adnexal mass, compressing neighboring structures, associatedwith increased alpha-fetoprotein and abdominal or pelvic pain. In the presentstudy, we report the case of a patient with fever and presence of abdominaltumor that was submitted to surgery for removal of extensive ovarian tumor.The importance of the best way of treating germ cell neoplasia, as well as thesize of the surgical piece removed from the patient, motivated the study andreport of the case.Keywords: pediatric surgery, ovarian cancer.

Radiotherapy induced intracranial growing teratoma syndrome in a pediatric germ cell tumor: a case report and literature review

Radiotherapy induced intracranial growing teratoma syndrome in a pediatric germ cell tumor: a case report and literature review

Pediatric Germ Cell Tumors: A Developmental Perspective.

Germ cell tumors (GCTs) arising in infants, children, and adolescents present a set of special challenges. GCTs make up about 3% of malignancies in children aged 0–18 and nearly 15% of cancers in adolescents. Epidemiologic and molecular evidence suggests that GCTs in young children likely represent a distinct biologic group as compared to GCTs of older adolescents and adults. Despite this difference, pediatric GCTs are typically treated with cisplatin-based multiagent regimens similar to those used in adults. There is evidence that children are particularly vulnerable to late effects of conventional therapy, including ototoxicity, pulmonary abnormalities, and secondary malignancies, motivating the search for molecular targets for novel therapies. Evidence is accumulating that the genes and mechanisms controlling normal germ cell development are particularly relevant to the understanding of germ cell tumorigenesis. Perturbations in the epigenetic program of germ cell differentiation, with resulting effects on the regulation of pluripotency, may contribute to the marked histologic variability of GCTs. Perturbations in the KIT receptor signaling pathway have been identified via next-generation sequencing studies and in genome-wide association studies of testicular cancer susceptibility. Here, we review these and other biological insights that may fuel further translational and clinical research in childhood GCTs.

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

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.

Clinical features, radiologic findings, and treatment of pediatric germ cell tumors involving the basal ganglia and thalamus: a retrospective series of 15 cases at a single center.

Pediatric germ cell tumors (GCTs) involving the basal ganglia and thalamus are relatively rare neoplasms which have not been extensively described. We here summarize the clinical and radiological features of a series of such tumors and discuss optimal treatment strategies based upon our experience. A total of 15 pediatric patients with basal ganglionic and thalamic GCTs were treated between 2011 and 2016 at West China Hospital. Epidemiological characteristics, clinical features, imaging findings, and treatment strategies were reviewed retrospectively. GCTs constituted 28% (15/53) of pediatric basal ganglionic and thalamic tumors in our institution between 2011 and 2016. There were 12 males and 3 females with mean age of 11.7±2.8years (range, 7-16years). The most common initial manifestation was hemiparesis (n=13, 86.7%), followed by headache (n=5, 33.3%), vomiting (n=3, 20.0%), cognitive disturbance (n=2, 13.3%), and seizure (n=1, 6.7%). No tumors were incidentally detected. The mean duration of the symptoms before diagnosis was 4.4±3.9months (range from 9days to 13months). The maximum diameters of the lesions ranged from 3.2 to 6.5cm (mean 4.7±1.1cm). Cysts were seen in tumors in MRIs in 11 patients (73%), intratumoral hemorrhages in 3 (20%), calcification in 2 (13%), and there was obstructive hydrocephalus in 1 (7%). Of note, hemiatrophy was observed in 9 cases (60.0%). The mean follow-up for the 15 patients was 28months (range, 9-54months), and no patients were lost. During the follow-up period, all patients (9 cases) with germinomas responded well to radiotherapy, and no recurrence was observed. Among 4 patients with mixed nongerminomatous germ cell tumor, 2 suffered tumor recurrence after treatment. Neurological deficits improved or remained unchanged in 12 patients but 3 developed new dysfunction including significant cognitive disturbance and hemiparesis. Pediatric GCTs in the basal ganglia and thalamus are not as rare as previously considered. Tumor markers should be tested routinely for tumors in these sites in young patients. Optimal treatment strategy based on accurate diagnosis and comprehensive clinical assessment should be recommended.

Family history of cancer in children and adolescents with germ cell tumours: a report from the Children\u2019s Oncology Group

Background:Studies of family history of cancer in paediatric germ cell tumours (GCTs) are few, and none has had sufficient sample size to specifically evaluate family history of GCT.Methods:We utilised family history data from a paediatric GCT study to calculate standardised incidence ratios (SIR) for GCT and other cancers using age- and sex-specific incidence rates from the SEER Program.Results:This analysis included 7998 relatives of paediatric GCT probands. We observed a higher number of GCT cases than expected in male and female relatives of probands (SIR=2.38, 95% CI 1.25, 3.51 for males; SIR=14.3, 95% CI 0.29, 28.4 for females). Further, we observed a particularly strong SIR for relatives of probands with intracranial GCT (SIR=8.07, 95% CI 3.51, 12.6). The SIR for relatives of probands with ovarian GCT was also elevated but did not reach statistical significance (SIR 4.35, 95% CI 0-9.27). Other notable associations include elevated SIRs for melanoma in male relatives and reduced SIRs for lymphatic/haematologic malignancies in male and female relatives.Conclusions:These results support the hypothesis that familial aggregation of GCT occurs in males and females.

Oropharyngeal teratoma in association with a diaphragmatic hernia

Abstract Pediatric germ cell tumors (GCT) rarely occur in the head and neck region and they are rarely associated with congenital anomalies. A 17 month old girl presented with a history of cough and change in voice for one month. Her chest x-ray and cross sectional imaging was suggestive of a mediastinal mass, right diaphragmatic hernia, and rib abnormality. Serologic and biomarkers were all negative for tumors. Surgical resection occurred with clear margins revealing a mass arising from the left hypopharnx via a pedunculated stalk. Histopathology was consistent with a mature teratoma including significant amounts of parathyroid tissue. She remains tumor free at 18 months follow up. To the best of our knowledge our patient is the third case in which a diaphragmatic hernia was reported in association with hypopharyngeal teratoma and our patient is the first to survive; this provides an opportunity to counsel families when this association is encountered.

Primary retroperitoneal yolk sac tumor

Primary retroperitoneal yolk sac tumour is very rare. 3 year old with rapidly progressing abdominal mass. CT heterogeneously enhancing large lesion with liver metastasis. HPE showed features suggestive of YST. Elevated AFP noted. Patient improved with surgery followed by chemotherapy. Paediatric germ cell tumours are highly curable form of cancer, but their diversity makes it challenging for the clinicians.

Two Tumors in 1: What Should be the Therapeutic Target? Pediatric Germ Cell Tumor With Somatic Malignant Transformation.

Germ cell tumors with somatic malignant transformation (GCT with SMT) are rare in children and poorly described. Data are missing to determine if therapies should target the GCT, the SMT compound, or both simultaneously. A retrospective national study was conducted in the Société Française des cancers de l'Enfant (SFCE) Centers. Medical records from patients aged 0 to 18 years diagnosed with GCT with SMT between 2000 and 2015 were analyzed. Any stages and primary sites were considered as well as synchronous and metachronous cases. Fifteen patients were identified. Thirteen patients had synchronous GCT with SMT. In the latter cases, primaries were ovary (5), mediastinum (3), pineal gland (3), sacrococcyx (1), and parametrium (1). SMT histologies were central primitive neuroectodermal tumor (5), embryonal rhabdomyosarcomas (3) or thyroid papillary adenocarcinoma, leukemia, poorly differentiated carcinoma, mixed sarcomas, and miscellaneous histology (1 case each). Chemotherapy was targeted against the GCT (3), the SMT (6), or both components (3). The last patient received surgery exclusively. Partial or complete response to chemotherapy was observed in 5/10 assessable cases: 2/3 patients treated with GCT-dedicated chemotherapy, 3/6 patients treated with SMT-dedicated therapy, and 0/1 treated with combined therapy. In addition, 2 patients with mediastinal GCT primary had metachronous SMT, with acute myeloid leukemia and thyroid papillary adenocarcinoma, 8 months and 8 years, respectively, after the diagnoses of GCT. Two patients (1 synchronous and 1 metachronous) were cured with surgery exclusively. At the end of follow-up, 6 patients died of their disease including all 4 with postsurgical macroscopic residue. GCT with SMT constitutes a very rare entity in children and adolescents. Surgical removal of the tumor is the cornerstone of the treatment and might be sufficient in selected cases. In the remaining cases, the best management is still unknown and should take into account both components and their respective chemosensitivity. Long-term surveillance is advised for patient with unresected teratoma as late transformation can occur.

The clinical impact of 18F-FDG PET/CT in extracranial pediatric germ cell tumors.

Extracranial germ cell tumors are an uncommon pediatric malignancy with limited information on the clinical impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the literature. The purpose of this study was to evaluate and compare the clinical impact on management of 18F-FDG PET/CT with diagnostic computed tomography (CT) in pediatric extracranial germ cell tumor. The list of 18F-FDG PET/CT performed for extracranial germ cell tumor between May 2007 and November 2015 was obtained from the nuclear medicine database. 18F-FDG PET/CT and concurrent diagnostic CT were obtained and independently reviewed. Additionally, the patients' charts were reviewed for duration of follow-up and biopsy when available. The impact of 18F-FDG PET/CT compared with diagnostic CT on staging and patient management was demonstrated by chart review, imaging findings and follow-up studies. During the study period, 9 children (5 males and 4 females; age range: 1.6-17years, mode age: 14years) had 11 18F-FDG PET/CT studies for the evaluation of germ cell tumor. Diagnostic CTs were available for comparison in 8 patients (10 18F-FDG PET/CT studies). The average interval between diagnostic CT and PET/CT was 7.2days (range: 0-37days). In total, five lesions concerning for active malignancy were identified on diagnostic CT while seven were identified on PET/CT. Overall, 18F-FDG PET/CT resulted in a change in management in 3 of the 9 patients (33%). 18F-FDG PET/CT had a significant impact on the management of pediatric germ cell tumors in this retrospective study. Continued multicenter studies are required secondary to the rarity of this tumor to demonstrate the benefit of 18F-FDG PET/CT in particular clinical scenarios.

Variants in BAK1, SPRY4, and GAB2 are associated with pediatric germ cell tumors: A report from the children's oncology group.

Germ cell tumors (GCT) are a rare form of childhood cancer that originate from the primordial germ cell. Recent genome-wide association studies (GWAS) have identified susceptibility alleles for adult testicular GCT (TGCT). We test whether these SNPs are associated with GCT in pediatric and adolescent populations. This case-parent triad study includes individuals with GCT diagnosed between ages 0 and 19. We evaluated 26 SNPs from GWAS of adult TGCT and estimated main effects for pediatric GCT within complete trios (N = 366) using the transmission disequilibrium test. We used Estimation of Maternal, Imprinting and interaction effects using Multinomial modelling to evaluate maternal effects in non-Hispanic white trios and dyads (N = 244). We accounted for multiple comparisons using a Bonferroni correction. A variant in SPRY4 (rs4624820) was associated with reduced risk of GCT (OR [95% CI]: 0.70 [0.57, 0.86]). A variant in BAK1 (rs210138) was positively associated with GCT (OR [95% CI]: 1.70 [1.32, 2.18]), with a strong estimated effect for testis tumors (OR [95% CI]: 3.31 [1.89, 5.79]). Finally, a SNP in GAB2 (rs948662) was associated with increased risk for GCT (OR [95% CI]: 1.56 [1.20, 2.03]). Nominal associations (P < 0.05) were noted for eight additional loci. A maternal effect was observed for KITLG SNP rs4474514 (OR [95% CI]: 1.66 [1.21, 2.28]) and a paternal parent-of-origin effect was observed for rs7221274 (P = 0.00007), near TEX14, RAD51C, and PPM1E. We observed associations between SNPs in SPRY4, BAK1, and GAB2 and GCTs. This analysis suggests there may be common genetic risk factors for GCT in all age groups.

Epidemiological study of paediatric germ cell tumours revealed the incidence and distribution that was expected, but a low mortality rate.

Germ cell tumours (GCTs) are a rare heterogeneous tumour group derived from primordial germ cells, which can be benign or malignant and occur in the gonads or extragonadally. This study mapped the paediatric GCTs in Denmark from 1984 to 2013 to study the incidence and outcome. We identified paediatric GCTs from the Danish Childhood Cancer and National Pathology Registries and reviewed the case records for patient characteristics, tumour characteristics and clinical outcome. We identified 403 (71% female) paediatric GCTs and the crude incidence was 1.43 per 100 000. Of these, 79 (20%) were malignant, 39 (10%) were potentially malignant and 285 (70%) were benign. Extragonadal GCTs (39%) were mainly observed in early childhood and were predominately sacrococcygeal teratomas. Gonadal GCTs (61%) in late childhood were most frequently mature teratomas in the ovaries. Nearly all patients underwent surgery. Of the malignant tumours, 62% were treated with chemotherapy. Radiotherapy was only administered to intracranial GCTs. In the cohort, 12 patients died (3%). Paediatric GCTs in Denmark were mainly benign and mortality was low, even for malignant tumours. We identified a peak of extragonadal GCTs in early childhood and a peak of gonadal GCTs in late childhood, which was comparable to previous reports.

Cystic Trophoblastic Tumor Arising in a Post Chemotherapy Pediatric Primary Central Nervous System Germ Cell Tumor

Cystic Trophoblastic Tumor Arising in a Post Chemotherapy Pediatric Primary Central Nervous System Germ Cell Tumor