Germ Cell Tumours in Children and Young Adults

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These tumours develop from germ cells. In the developing embryo germ cells migrate to the ovaries or testicles and form the ova (egg cells) or sperm cells. Germ cell tumours occur where these cells become cancerous. These tumours typically express high levels of alphafetoprotein (AFP). Germ cell tumours are most common in children and young adults, there are different sub-types including endodermal tumours (mostly found in children), dysgerminoma, teratoma, and seminoma (young men). The most common location of these tumours are the ovaries (in females) or testicles (in males). However, they can also develop in other parts of the body such as the sacrococcygeal region, brain, abdomen and other sites - this may occur when some of the germ cells in the embryo did not migrate properly. For information on germ cell tumours of the brain see the section on brain tumours. Note: germ cell tumours in children tend to be quite different to those in adults.

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Latest Research Publications

Information Patients and Family (6 links)

 Childhood Extracranial Germ Cell Tumors Treatment

National Cancer Institute
PDQ summaries are written and frequently updated by editorial boards of experts Further info.


 Germ Cell Tumor - Childhood

Cancer.Net
Content is peer reviewed and Cancer.Net has an Editorial Board of experts and advocates. Content is reviewed annually or as needed. Further info.


 Germ cell tumours in children

Macmillan Cancer Support
Content is developed by a team of information development nurses and content editors, and reviewed by health professionals. Further info.


 Germ cell tumors

Children's Cancer Research Fund
Overview

 Germ Cell Tumors

Childrens' Oncology Group
Includes information about childhood germcell tumors, with sections on newly diagnosed, in treatment and after treatment.

 Germ Cell Tumors

Johns Hopkins Medical Institute

Information for Health Professionals / Researchers (4 links)

• PubMed search for publications about Germ Cell Tumours, child - Limit search to: [Reviews]

  PubMed Central search for free-access publications about Germ Cell Tumours, child
  MeSH term: Neoplasms, Germ Cell and Embryonal
  US National Library of Medicine
  PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.

 Childhood Extracranial Germ Cell Tumors Treatment

National Cancer Institute
PDQ summaries are written and frequently updated by editorial boards of experts Further info.


 Germ Cell, Trophoblastic and Other Gonadal Neoplasms

SEER, National Cancer Institute
Part of a SEER report on statistical trends and risk factors associated with childhood cancers. From: Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975-1995. (PDF)

 Pediatric Teratomas and Other Germ Cell Tumors

Medscape
Referenced article by Stanton Adkins III, MD covering background, presentation, diagnosis, workup, treatment and follow-up.

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

BACKGROUND: Central nervous system (CNS) germ cell tumors account for 3 % of all pediatric brain tumors in the USA. Presenting symptoms are typically location based with pineal tumors presenting with obstructive hydrocephalus and suprasellar tumors with hypothalamic/pituitary dysfunction and ophthalmologic abnormalities. Psychiatric manifestations such as psychosis and behavioral changes are atypical presentations of CNS germ cell tumors, with only 11 previously reported cases.
METHODS: This is a retrospective case series describing patients with CNS germ cell tumors with an atypical presentation including psychiatric manifestations. Information regarding clinical presentation, treatment course, and outcome were obtained.
RESULTS: We report seven patients who presented with psychiatric symptoms consisting of psychomotor delay as well as behavioral and mood changes. Six of the seven patients were diagnosed ≥6 months after onset of psychiatric symptoms. All of the seven are alive but five continue to have neurologic and psychiatric issues post treatment.
CONCLUSIONS: Atypical presentations of CNS germ cell tumors can delay diagnosis and treatment and may be secondary to atypical locations as well as endocrine dysfunction manifesting as psychiatric symptoms. Delayed diagnosis did not appear to affect survival but earlier diagnosis may potentially be associated with better neurologic and psychiatric outcome. Patients who present with these symptoms and atypical neuroimaging should have a thorough evaluation for CNS germ cell tumors including serum and CSF markers. Clinicians should be aware of these less common presentations to aid in prompt diagnosis and treatment.

Related: Childhood Brain Tumours Childhood Brain Tumors

PURPOSE: Germ cell tumour (GCT) aetiology is uncertain and comprehensive epidemiological studies of GCT incidence are few.
METHODS: Nationwide data on all malignant GCTs notified to Australian population-based cancer registries during 1982-2011 were obtained. Age- and sex-specific, and World age-standardised incidence rates were calculated for paediatric (0-14) and adult (15+) cases using the latest WHO subtype classification scheme. Temporal trends were examined using Joinpoint regression.
RESULTS: There were 17,279 GCTs (552 paediatric, 16,727 adult). Age-specific incidence in males (all histologies combined) was bimodal, with peaks during infancy for most sites, and second, larger, peaks during young adulthood. Incidence of ovarian tumours peaked at age 15-19. Around half of paediatric tumours were extragonadal, whereas adult tumours were mostly gonadal. Yolk sac tumours and teratomas predominated in infants, whereas germinomas became more frequent towards adulthood. Increasing incidence trends for some adult gonadal tumours have stabilised; the trend for male extragonadal tumours is also declining.
CONCLUSION: Broad similarities in the shape of age-specific incidence curves, particularly for gonadal, central nervous system, and mediastinal tumours provide epidemiological support for commonalities in aetiology among clinically disparate GCT subtypes. Differences in peak ages reflect underlying subtype-specific biological differences. Declining incidence trends for some adult gonadal tumours accords with the global transition in GCT incidence, and supports the possibility of a reduction in prevalence of shared aetiological exposures.

Related: Australia

PURPOSE: We describe the results of a risk-adapted, response-based therapeutic approach from the Brazilian GCT-99 study on germ cell tumors.
PATIENTS AND METHODS: From May 1999 to October 2009, 579 participants were enrolled in the Brazilian GCT-99 study. Treatment, defined as specific chemotherapy regimen and number of cycles, was allocated by means of risk-group assignment at diagnosis with consideration for stage and primary tumor site. Patients at low risk received no chemotherapy. Patients at intermediate risk (IR) with a good response (GR) received four cycles of platinum and etoposide (PE), for total doses of platinum 420 mg/m(2) and etoposide 2,040 mg/m(2). Patients at IR with a partial response (PR) received three cycles of PE plus three cycles of ifosfamide, vinblastine, and bleomycin. Patients at high risk (HR) with a GR received four cycles of PE and ifosfamide (PEI) at total doses of platinum 420 mg/m(2), etoposide 1,200 mg/m(2), and ifosfamide 30 g/m(2). Patients at HR with a PR received six cycles of PEI.
RESULTS: The risk-group distribution was 213 LR, 138 IR, and 129 HR for 480 evaluable patients. Overall survival (OS) and event-free survival (EFS) rates at 10 years were, respectively, 90% and 88.6% in the IR-GR group (n = 126) and 74.1% and 74.1% in the IR-PR group (n = 12). Ten-year rates for the HR-GR group (n = 86) were an OS of 66.8% and an EFS of 62.5%. The HR-PR group (n = 43) had an OS of 74.8% and an EFS of 73.4%. In univariable and multivariable analysis, increased serum lactate dehydrogenase level and histology for a metastatic immature teratoma were prognostic of a worsened outcome.
CONCLUSION: Reduction of therapy to two drugs did not compromise survival outcomes for patients in the IR-GR group, and escalation of therapy with PEI did not significantly improve OS and EFS in patients at HR.

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BACKGROUND: The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we developed a robust technical pipeline to quantify these miRNAs in the serum and cerebrospinal fluid (CSF). The pipeline was used in samples from a cohort of exclusively paediatric patients with gonadal and extragonadal malignant GCTs, compared with appropriate tumour and non-tumour control groups.
METHODS: We developed a method for miRNA quantification that enabled sample adequacy assessment and reliable data normalisation. We performed qRT-PCR profiling for miR-371-373 and miR-302/367 cluster miRNAs in a total of 45 serum and CSF samples, obtained from 25 paediatric patients.
RESULTS: The exogenous non-human spike-in cel-miR-39-3p and the endogenous housekeeper miR-30b-5p were optimal for obtaining robust serum and CSF qRT-PCR quantification. A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early detection of relapse of a testicular mixed malignant GCT; and (iii) distinguished intracranial malignant GCT from intracranial non-GCT tumours at diagnosis, using CSF and serum samples.
CONCLUSIONS: The pipeline we have developed is robust, scalable and transferable. It potentially promises to improve clinical management of paediatric (and adult) malignant GCTs.

Related: Brain and Spinal Cord Tumours MicroRNAs Ovarian Cancer Testicular Cancer

Evidence from our previous study suggested that the incidence of germ cell neoplasms in children and adolescents is increasing. The objectives of this analysis were to quantify this trend in patients aged 0-9 and 10-19 years (pre-pubertal and adolescent groups, respectively) and compare rates in Taiwan according to geographic distribution. Germ cell neoplasm frequencies among 1267 patients aged 0-19 years spanning 1995-2009 were obtained from the population-based Taiwan Cancer Registry. The incidence patterns according to sex, age, disease subgroup, and geographic distribution were analyzed. The incidence rates in the pre-pubertal and adolescent groups were 10.58 and 16.06 per million person-years, respectively. The overall rates increased significantly by 3.2% annually in the adolescent group during the 15-year study period, and increased only among the males. In contrast, no change in trend was observed in the pre-pubertal group. Subgroup analysis showed significant upward trends in the incidence rates of intracranial/intraspinal and testicular germ cell tumors (GCTs) in the adolescent males and extracranial/extragonadal GCTs in the pre-pubertal boys. The most striking differences between the study population and white Americans were that the rates of testicular GCTs were 5-fold higher and 4-fold lower in the Taiwanese pre-pubertal and adolescent groups, respectively. Significantly higher rates were found in Hualien and Chiayi Counties compared with the other areas of Taiwan. The upward trend of testicular GCTs in the adolescent males is consistent with findings from Western countries. The underlying causes that led to the high rate of testicular GCTs in the pre-pubertal boys and significantly higher rates in specific counties warrant further investigation.

Related: Testicular Cancer

Testicular germ cell tumors make up 0.5% of pediatric malignancies, and 14% of adolescent malignancies. Young boys have primarily pure teratoma and pure yolk sac histologies; however, adolescent histology is mostly mixed nonseminomatous germ cell tumor. Surgical excision of the primary tumor is the crux of treatment. Chemotherapy, retroperitoneal lymph node dissection, and targeted treatment of distant metastases make even widely disseminated disease treatable. Since the discovery of platinum-based chemotherapy, testicular germ cell tumors are a highly curable disease. However, adolescents remain the group with the highest mortality. Focus has expanded beyond survival to emphasize quality of life issues when optimizing treatment algorithms.

Related: Testicular Cancer

OBJECTIVE: To analyze the oncologic and reproductive outcomes of pediatric and young adolescents with malignant ovarian germ cell tumors (MOGCTs).
METHODS: Pediatric or young adolescent girls aged 16years or under with MOGCT were eligible for this study.
RESULTS: Forty-two pediatric or adolescent girls with MOGCT met the inclusion criteria. The median age was 12years (range, 6-16years) and 29 patients were premenarchal. The most common histologic type was immature teratoma, and 30 patients (54.3%) had stage I MOGCT. All patients underwent fertility-sparing surgery, which was defined as the preservation of at least one adnexa and the uterus. No patient had residual disease after surgery. Thirteen patients had tumor spillage, two patients had a positive peritoneal cytology, and two patients had lymph node metastasis. After surgery, 31 patients received adjuvant chemotherapy with bleomyocin, etoposide, and cisplatin (BEP) (median, 4cycles; range, 1-6 cycles). After a median follow-up time of 93months (range, 22-217 months), six patients had a recurrence of the disease, and one patient died. The 5-year disease-free and overall survival rates were 85% and 97%, respectively. Among the surviving 41 patients, seven were premenarchal, 30 had regular menstruation, and three had irregular menstruation. No patient had premature ovarian failure.
CONCLUSION: All patients received uniform treatment consisting of fertility-sparing complete cytoreductive surgery followed by BEP chemotherapy. Regardless of histologic type and FIGO stage, the oncologic outcomes were excellent and the reproductive outcomes were favorable.

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PURPOSE: The purpose of this study was to determine prognostic factors correlating with outcome in boys with Stage I malignant testicular germ cell tumors (MTGCT) initially managed with surveillance after surgical resection.
METHODS: Between November 2003 and July 2011, 80 boys 0-15 years with Stage I MTGCT were enrolled in Children's Oncology Group Study AGCT0132. Those with residual or recurrent disease were treated with chemotherapy.
RESULTS: Characteristics include: age (65, 0-5 years and 15, 11+years), pure YST (93.9%, 0-5 years and 0%, 11+years); and lymphovascular invasion (LVI) (50.6% present vs. 49.4% absent). At median follow-up of 4.94 years, 19 had persistent or recurrent disease, all detected by elevated AFP at a median of 87 days after study enrollment. The outcome from enrollment was 4-year EFS 74% (95% CI: 63%-83%) and 4-year OS 100%. 4-year EFS was improved with younger age (<11 years, 80% vs. 11+years, 48%, p<0.01); pure YST vs. mixed histology (81% vs. 45%, p<0.01), and lack of LVI (84% vs. 62%, p=0.03).
CONCLUSIONS: Boys with Stage I MTGCT have excellent overall survival when treated with surgery alone. Age greater than 10 years, mixed histology and presence of LVI are each associated with relapse and may allow identification of high risk boys at time of enrollment.

Related: Testicular Cancer

PURPOSE: To risk stratify malignant extracranial pediatric germ cell tumors (GCTs).
PATIENTS AND METHODS: Data from seven GCT trials conducted by the Children's Oncology Group (United States) or the Children's Cancer and Leukemia Group (United Kingdom) between 1985 and 2009 were merged to create a data set of patients with stage II to IV disease treated with platinum-based therapy. A parametric cure model was used to evaluate the prognostic importance of age, tumor site, stage, histology, tumor markers, and treatment regimen and estimate the percentage of patients who achieved long-term disease-free (LTDF) survival in each subgroup of the final model. Validation of the model was conducted using the bootstrap method.
RESULTS: In multivariable analysis of 519 patients with GCTs, stage IV disease (P = .001), age ≥ 11 years (P < .001), and tumor site (P < .001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) ≥ 10,000 ng/mL was associated with worse outcome, whereas pure yolk sac tumor (YST) was associated with better outcome, although neither met criteria for statistical significance. The analysis identified a group of patients age > 11 years with either stage III to IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival < 70%. A bootstrap procedure showed retention of age, tumor site, and stage in > 94%, AFP in 12%, and YST in 27% of the replications.
CONCLUSION: Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric GCTs that identifies a poor-risk group warranting intensified therapy.

Related: USA

Four cases are reported meeting the criteria of a pediatric (i.e., Type I) testicular germ cell tumor (TGCT), apart from the age of presentation, which is beyond childhood. The tumors encompass the full spectrum of histologies of pediatric TGCT: teratoma, yolk sac tumor, and various combinations of the two, and lack intratubular germ cell neoplasia/carcinoma in situ in the adjacent parenchyma. The neoplasms are (near)diploid, and lack gain of 12p, typical for seminomas and non-seminomas of the testis of adolescents and adults (i.e., Type II). It is proposed that these neoplasms are therefore late appearing pediatric (Type I) TGCT. The present report broadens the concept of earlier reported benign teratomas of the post-pubertal testis to the full spectrum of pediatric TGCT. The possible wide age range of pediatric TGCT, demonstrated in this study, lends credence to the concept that TGCT should according to their pathogenesis be classified into the previously proposed types. This classification is clinically relevant, because Type I mature teratomas are benign tumors, which are candidates for testis conserving surgery, as opposed to Type II mature teratomas, which have to be treated as Type II (malignant) non-seminomas.

Related: FISH Testicular Cancer

Genomic and protein-coding transcriptomic data have suggested that germ cell tumours (GCTs) of childhood are biologically distinct from those of adulthood. Global messenger RNA profiles segregate malignant GCTs primarily by histology, but then also by age, with numerous transcripts showing age-related differential expression. Such differences are likely to account for the heterogeneous clinico-pathological behaviour of paediatric and adult malignant GCTs. In contrast, as global microRNA signatures of human tumours reflect their developmental lineage, we hypothesized that microRNA profiles would identify common biological abnormalities in all malignant GCTs owing to their presumed shared origin from primordial germ cells. MicroRNAs are short, non-protein-coding RNAs that regulate gene expression via translational repression and/or mRNA degradation. We showed that all malignant GCTs over-express the miR-371-373 and miR-302/367 clusters, regardless of patient age, histological subtype or anatomical tumour site. Furthermore, bioinformatic approaches and subsequent Gene Ontology analysis revealed that these two over-expressed microRNAs clusters co-ordinately down-regulated genes involved in biologically significant pathways in malignant GCTs. The translational potential of this finding has been demonstrated with the detection of elevated serum levels of miR-371-373 and miR-302/367 microRNAs at the time of malignant GCT diagnosis, with levels falling after treatment. The tumour-suppressor let-7 microRNA family has also been shown to be universally down-regulated in malignant GCTs, because of abundant expression of the regulatory gene LIN28. Low let-7 levels resulted in up-regulation of oncogenes including MYCN, AURKB and LIN28 itself, the latter through a direct feedback mechanism. Targeting LIN28, or restoring let-7 levels, both led to effective inhibition of this pathway. In summary, paediatric malignant GCTs show biological differences from their adult counterparts at a genomic and protein-coding transcriptome level, whereas they both display very similar microRNA expression profiles. These similarities and differences may be exploited for diagnostic and/or therapeutic purposes.

Related: MicroRNAs Ovarian Cancer Testicular Cancer

Paediatric germ cell tumours (GCTs) are rare and account for less than 3 % of childhood cancers. Like adult GCTs, they probably originate from primordial germ cells, but the pattern of histopathological types is different, and they occur predominantly in extragonadal sites along the body midline. Because they are rare, histology of paediatric GCTs is poorly documented, and it remains unclear to what extent they differ from adult GCTs. We have analysed 35 paediatric germ cell tumours and 5 gonadal sex-cord stromal tumours from prepubertal patients aged 0-15 years, to gain further knowledge, elaborate on clinical-pathological associations and better understand their developmental divergence. The tumours were screened for expression of stemness-related factors (OCT4, AP-2γ, SOX2), classical yolk sac tumours (YSTs; AFP, SALL4), GCTs (HCG, PLAP, PDPN/D2-40), as well as markers for sex-cord stromal tumour (PDPN, GATA4). All YSTs expressed AFP and SALL4, with GATA4 present in 13/14. The majority of teratomas expressed SOX2 and PDPN, whereas SALL4 was found in 8/13 immature teratomas. Adult seminoma markers AP-2γ, OCT4, SALL4 and PDPN were all expressed in dysgerminoma. We further report a previously unrecognised pathogenetic relationship between AFP and SALL4 in YST in that different populations of YST cells express either SALL4 or AFP, which suggests variable differentiation status. We also show that AP-2γ is expressed in the granulosa layer of ovarian follicles and weakly expressed in immature but not in mature granulosa cell tumours. Our findings indicate that the expression pattern of these antigens is similar between paediatric and adult GCTs, even though they develop along different developmental trajectories.

Related: Ovarian Cancer Testicular Cancer AFP

BACKGROUND/AIMS: Central nervous system germ cell tumors (CNS-GCTs) are relatively rare. While their incidence was thought to be higher in East Asia than the USA, recent evidence suggests the difference between Japan and the USA is not statistically significant. The aim of this study was to determine the rate of pediatric primary CNS-GCTs in Kumamoto prefecture, Japan.
METHODS: We surveyed 6,615 new cases of primary intracranial tumors diagnosed in Kumamoto prefecture between 1989 and 2011. Among these, 251 (3.8%) occurred in patients younger than 15 years. The age-adjusted incidence rates were calculated by the direct method using 5-year age groupings; the incidence in the total Japanese population in the year 2000 was the standard.
RESULTS: During the 23-year period, 70 cases of primary GCT were diagnosed. Of these tumors, 31 (44.3%) arose in patients aged between 0 and 14 years (22 boys, 9 girls). Their tumor location was pineal in 45.2%; the other sites were nonpineal. There were more germinomas (64.5%) than nongerminomas (35.5%) in this group. The age-adjusted annual incidence rate was 0.45 cases (boys: 0.64, girls: 0.28) per 10(5) children. At 2.29, the ratio of CNS-GCTs was higher in these boys than girls. Our data showed higher rates than data from CBTRUS 2012 (0.18/10(5)), SEER 2008 (0.15/10(5)) and Germany (0.10/10(5)).
CONCLUSIONS: Our survey showed that the incidence of primary CNS-GCTs in children was higher in Kumamoto prefecture than in the USA and other Western countries, suggesting that racial backgrounds play a role.

Related: Childhood Brain Tumours Childhood Brain Tumors

Pediatric germ cell tumors (GCTs) are rare neoplasms arising predominantly in the gonads and sacrococcygeal, mediastinal, and intracranial localizations. In this article, we review current knowledge of pathogenesis of pediatric GCTs, which differs from adult/adolescent GCTs. One distinctive feature is the absence of a progenitor stage, such as carcinoma in situ or gonadoblastoma, which are seen in adult/adolescent GCTs, except spermatocytic seminoma. The primordial germ cell (PGC) is the suggested origin of all GCTs, with variations in histology reflecting differentiation stage. Expression of pluripotency transcription factors OCT-3/4, NANOG, and AP-2γ in germinomas/seminomas/dysgerminomas is consistent with retaining a germ cell phenotype. Teratomas, in contrast, develop through a pathway of aberrant somatic differentiation of immature germ cells, and the yolk sac tumors and choriocarcinomas result from abnormal extraembryonic differentiation. In pediatric GCTs, origin is suggested at an earlier developmental stage because of predisposing genetic factors, although responsible genes remain largely unknown. Some extragonadal GCTs have been linked to overexpression of the KIT/KITLG system, allowing for survival of aberrantly migrated ectopic PGCs. Infant gonadal/sacrococcygeal GCTs may be caused by apoptosis-related pathways, consistent with an association with polymorphisms in BAK1. Although recent advances have identified candidate pathways, further effort is needed to answer central questions of pathogenesis of these fascinating tumors.

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Primary ovarian malignant melanoma arising in teratomatous component of germ cell tumors is seen extremely rare with most reports being only of single cases and small series in reproductive aged woman and mostly from cystic teratoma, whereas information on pediatric presentation is sparse. This case is reported for being extremely rare tumor.

Related: Melanoma Ovarian Cancer

BACKGROUND: Ovarian tumors in the pediatric age group are not infrequent. Germ-cell tumors are the commonest ovarian neoplasm in the first two decades of life. Sex cord-stromal tumors are the most common ovarian tumors to cause precocious puberty in girls.
PATIENTS AND METHODS: This retrospective study included all managed cases of malignant germ-cell and sex cord-stromal tumors in the pediatric age (less than 18 years). The medical records of the admitted cases from first of January, 2008 to 31 December, 2012 were reviewed and the following information was collected: patient age, clinical presentation, surgical stage, tumor histology, therapy, clinical course, and outcome. Serum alpha-fetoprotien on admission was studied.
RESULTS: The study included 42 pediatric cases of germ-cell and granulosa cell tumors of the ovary. Mean age of the cases was 11.26 years (range: 7-15 years). Abdominal pain was the commonest presentation. Twenty-two cases (52.4%) were diagnosed as stage I disease. Twenty-eight cases (66.7%) were exposed to fertility sparing surgery. Age of the patient and site of tumor were significantly correlated to the survival (p value: 0.04 & 0.09 respectively). The correlations of stage of the disease, use of pre-operative chemotherapy, and type of surgical interference were highly significant (P value: 0.007, 0.001, and 0.001 respectively). Tumor size and histologic types were not significantly correlated to survival (P value: 0.19 & 0.67 respectively).
CONCLUSION: The cumulative survival rate was 76.2%. The correlations of stage of the disease, use of pre-operative chemotherapy, and type of surgical interference were highly significant. Tumor size and histologic types were not significantly correlated to survival. Initial level of alpha-fetoprotein was not significantly correlated to survival or recurrence.

Related: Ovarian Cancer

PURPOSE: To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection.
PATIENTS AND METHODS: Between November 2003 and July 2011, girls age 0 to 16 years with stage I MOGCT were enrolled onto Children's Oncology Group study AGCT0132. Required histology included yolk sac, embryonal carcinoma, or choriocarcinoma. Surveillance included measurement of serum tumor markers and radiologic imaging at defined intervals. In those with residual or recurrent disease, chemotherapy with compressed PEB (cisplatin, etoposide, and bleomycin) was initiated every 3 weeks for three cycles (cisplatin 33 mg/m(2) on days 1 to 3, etoposide 167 mg/m(2) on days 1 to 3, bleomycin 15 U/m(2) on day 1). Survivor functions for event-free survival (EFS) and OS were estimated using the Kaplan-Meier method.
RESULTS: Twenty-five girls (median age, 12 years) with stage I MOGCT were enrolled onto AGCT0132. Twenty-three patients had elevated alpha-fetoprotein (AFP) at diagnosis. Predominant histology was yolk sac. After a median follow-up of 42 months, 12 patients had evidence of persistent or recurrent disease (4-year EFS, 52%; 95% CI, 31% to 69%). Median time to recurrence was 2 months. All patients had elevated AFP at recurrence; six had localized disease, two had metastatic disease, and four had tumor marker elevation only. Eleven of 12 patients experiencing relapse received successful salvage chemotherapy (4-year OS, 96%; 95% CI, 74% to 99%).
CONCLUSION: Fifty percent of patients with stage I pediatric MOGCT can be spared chemotherapy; treatment for those who experience recurrence preserves OS. Further study is needed to identify the factors that predict recurrence and whether this strategy can be extended successfully to older adolescents and young adults.

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BACKGROUND: Testicular germ cell tumors (T-GCTs) occur from infancy to adulthood, and are the most common solid tumor in adolescent and young adult males. Traditionally, pediatric T-GCTs were perceived as more indolent than adult T-GCTs. However, there are few studies comparing these groups and none that specifically evaluate adolescents.
METHODS: An institutional database of T-GCT patients was reviewed and patients were categorized into Pediatric, aged 0-12 years, Adolescent, aged 13-19 years, and Adult, older than 20 years, cohorts. Demographics, tumor characteristics, disease stage, treatment, event-free survival (EFS), and overall survival (OS) were compared between groups.
RESULTS: Overall, 413 patients (20 pediatric, 39 adolescent, 354 adult) met study criteria and were followed for a median of 2.0 years (0.1-23.6). Adolescents presented with more advanced stage than children (P = 0.018) or adults (P = 0.008). There was a higher rate of events in Adolescents (13, 33.3%) than in Adults (61, 17.2%) or Children (2, 10.0%). Three-year EFS was 87.2% in the Pediatric group, 59.9% in Adolescents and 80.0% in Adults (P = 0.011). In a multivariate analysis, controlling for stage, IGCCCG risk, and histology, the hazard ratio (HR) for an event was: 1 (Reference) for Adults, HR = 0.82 (95% CI 0.19-3.46; P = 0.33) for the Pediatric group, and HR = 2.22 (95% CI 1.21-4.07; P = 0.01) for Adolescents. Five-year OS was 100% in the Pediatric group, 84.8% in Adolescents, and 92.8% in Adults (P = 0.388).
CONCLUSION: Lower EFS in adolescent T-GCT patients was observed than in either children or adults. Elucidating factors associated with inferior outcomes in adolescents is an important focus of future research.

Related: Testicular Cancer

BACKGROUND: There is suggestion that testicular microlithiasis predicts risk of testicular malignancy, especially testicular germ cell tumors. This association remains uncertain.
OBJECTIVE: We retrospectively reviewed testicular germ cell tumor occurrence in patients with testicular microlithiasis to assess this association and determined the prevalence of testicular microlithiasis in symptomatic boys.
MATERIALS AND METHODS: This study was IRB and HIPAA compliant. Two-thousand six-hundred twenty-five testicular US exams performed on 2,266 children (younger than 19 years of age) in our institution from 2000 through 2011 were reviewed for presence of testicular microlithiasis and masses. Testicular microlithiasis was defined as presence of five or more testicular microcalcifications on a single US image. Incidence of testicular germ cell tumors was calculated in a group of patients with testicular microlithiasis and in a control group without testicular microlithiasis. Relative risk, odds ratio, 90% and 95%CI were calculated.
RESULTS: Eighty-seven patients out of 2,266 had testicular microlithiasis. One child was found to have both testicular germ cell tumor and testicular microlithiasis. In 2,179 children without testicular microlithiasis, 8 had testicular germ cell tumors. Incidence of testicular microlithiasis was 3.8%. Incidence of testicular germ cell tumors in testicular microlithiasis patients was 1.2%, and 0.38% in non-testicular microlithiasis patients. Relative risk of testicular germ cell tumors in testicular microlithiasis patients vs. non-testicular microlithiasis patients was 3.13 (90%CI: 0.55-17.76; 95%CI: 0.40-24.76), odds ratio 3.16 (90%CI: 0.55-18.32; 95%CI: 0.39-25.5).
CONCLUSION: There is no association between testicular microlithiasis and testicular germ cell tumors. We had hoped to do a meta-analysis, but only two studies had a sufficient case control group of non-testicular microlithiasis patients.

Related: Testicular Cancer

PURPOSE: Some children with extracranial germ cell tumors (GCT) relapse after or do not respond to first-line treatment combining chemotherapy and surgery, of whom very few experience long-term survival despite multimodal salvage treatment.
METHODS: This prospective study, part of the French TGM95 Protocol for non-seminomatous GCT (NSGCT), included 19 (7%) children with malignant refractory or recurrent extracranial NSGCT who were studied to identify prognostic factors and determine the best salvage treatment.
RESULTS: At the end of the first-line treatment, 10 and 9 children were in complete and incomplete remission, respectively. Events occurred within 2 years (5-23 months) after initial diagnosis. A progression was observed in 13 patients at least in one site initially involved. Two patients had a purely biological relapse (increase in isolated markers), and four patients had a purely metastatic relapse (brain location in three cases). After salvage treatment combining surgery and various types of chemotherapy (including high-dose chemotherapy (HDCT) in 10 cases), the 5-year event-free survival and overall survival rates were of 26% (95%CI: 9.6-46.8%) and 32% (95%CI: 12.9-52.2%), respectively. Patients who underwent complete surgery (or without any detectable tumor) had higher survival rate than patients who underwent partial surgery or for whom surgery was not feasible (P = 0.0003) at first relapse while this rate was similar between patients treated or not with HDCT.
CONCLUSION: In pediatric recurrent or refractory NSGCT, complete excision of the tumor appears essential. The role of HDCT remains debated.

Related: Bleomycin Cisplatin Etoposide Ifosfamide Testicular Cancer Vinblastine

The present study evaluated the feasibility and effectiveness of myeloablative high-dose chemotherapy and autologous stem cell transplantation in patients with relapsed or progressed central nervous system germ cell tumors (CNS-GCTs). Eleven patients with non-germinomatous germ cell tumors and nine patients with germinomas were enrolled. Patients received between two and eight cycles of conventional chemotherapy prior to HDCT/autoSCT with or without radiotherapy. Overall, 16 patients proceeded to the first HDCT/autoSCT, and nine proceeded to the second HDCT/autoSCT. CTE (carboplatin-thiotepa-etoposide) and cyclophosphamide-melphalan (CM) regimens were used for the first and second HDCT, respectively. Toxicities during HDCT/autoSCT were acceptable, and there were no treatment-related deaths. Twelve patients experienced relapse or progression; however, four patients with germinomas remain alive after subsequent RT. Therefore, a total of 12 patients (four NGGCTs and eight germinomas) remain alive with a median follow-up of 47 months (range 22-90) after relapse or progression. The probability of 3-year overall survival was 59.1 ± 11.2 % (36.4 ± 14.5 % for NGGCTs vs. 88.9 ± 10.5 % for germinomas, P = 0.028). RT, particularly craniospinal RT, was associated with a better tumor response prior to HDCT/autoSCT and a better final outcome. In conclusion, HDCT/autoSCT was feasible, and survival rates were encouraging. Further study with a larger cohort of patients is needed to elucidate the role of HDCT/autoSCT in the treatment of relapsed or progressed CNS-GCTs.

Related: Carboplatin Brain and Spinal Cord Tumours Cyclophosphamide Etoposide Melphalan Thiotepa

We report on a 14-year-old boy with bilateral testicular microlithiasis and a right-sided testicular tumor. Tumor markers alpha-fetoprotein (AFP) and β-human chorionic gonadrotropin (β-hCG) levels were elevated and orchiectomy revealed a mixed germ cell tumor consisting of embryonal carcinoma, yolk sac tumor, choriocarcinoma, and mature teratoma. The patient had no evidence of metastatic disease. Although there is a strong association between testicular microlithiasis and testicular tumor, the pediatric literature is varying in the recommended surveillance of these patients. The literature and management of pediatric patients with testicular microlithiasis is herein reviewed.

Related: Testicular Cancer

A retrospective analysis was conducted on consecutive patients with intracranial germ cell tumours diagnosed and treated from 1 January 1997 to 31 December 2007 to assess and determine demographic factors and treatment outcomes of children with these tumours treated in a major paediatric referral hospital in Australia. In this study, intracranial germ cell tumours represented 4.8% of paediatric brain tumours seen. Of the 21 patients identified, 15 (71.4%) were diagnosed with pure germinoma and six (28.6%) with non-germinomatous germ cell tumours (NGGCT) or mixed tumours. One patient received chemotherapy alone, two patients were treated with radiation alone and the remaining 18 received a combination of chemotherapy and radiotherapy. A total of 33 neurosurgical operations were performed with 15 biopsies via open, endoscopic or transphenoidal means; nine open resections; and nine procedures for hydrocephalus comprising seven third ventriculostomies and two ventriculoperitoneal shunts. For patients with pure germinomas, the 5-year disease-free rate (DFS) was 93.3%, and overall survival (OS) rate was 100% compared to NGGCT or mixed tumours (DFS 50%; OS 50%) (DFS p=0.019, OS p=0.004). The data presented show that pure germinomas carry a favourable prognosis. The data also support that treatment with induction chemotherapy followed by dose-attenuated radiotherapy is an effective alternative with results comparable to historical controls treated with craniospinal irradiation. Although chemoradiotherapy has become the mainstay of treatment in intracranial germ cell tumours, surgery remains integral to the management of this condition. Surgery remains important in establishing the histological diagnosis, as well as in the treatment of hydrocephalus. Furthermore, debulking procedures may be advocated in NGGCT as they are often resistant to chemotherapy.

Related: Australia Childhood Brain Tumours Childhood Brain Tumors

Germ cell tumors (GCTs) are thought to develop from totipotent primordial germ cells. Although the epithelial cell adhesion molecule (EPCAM) is expressed on embryonic stem cells as well as different tumor cells, it has not yet been extensively studied in GCTs. We analyzed EPCAM expression by quantitative RT-PCR in 48 fresh-frozen GCT specimens of different histology (10 mature teratoma, MT; 6 immature teratoma, IT; 7 dysgerminoma; 6 mixed malignant GCTs; 19 yolk sac tumor, YST) and in the GCT cell lines NCCIT, TE76.T, JAR and 2102Ep, and correlated its expression with AFP and hCG protein levels, histologic differentiation, and clinical follow-up data. EPCAM protein was visualized by immunohistochemistry of selected corresponding paraffin embedded tumor tissues. EPCAM was expressed in malignant but not in benign GCTs irrespective of age, sex, site and clinical stage of tumor (P = 0.001). In primary teratomas, EPCAM expression increased with their grade of immaturity (mean 2(-ΔCt) values: MT 0.23, IT 1.61, P = 0.007) and significantly correlated with serum AFP (P = 0.03) and hCG (P = 0.03) levels in malignant GCTs. Particularly high EPCAM levels were found in nonseminomatous GCTs such as YSTs (8.49) and choriocarcinoma (13.54). Immunohistochemical analysis verified gene expression data showing a distinct EPCAM staining in YST. Similarly in vitro, highest EPCAM expression was measured in GCT cell lines comprising yolk sac (2102Ep: 5.59) or choriocarcinoma (JAR: 10.65) components. This first comprehensive analysis of EPCAM in GCTs revealed high EPCAM expression in YSTs and choriocarcinomas. Thus, these nonseminomatous GCTs may be interesting targets for EPCAM immunotherapy, which has to be evaluated in further studies.

Related: EPCAM

BACKGROUND: While cisplatin is considered superior to carboplatin for the treatment of malignant germ cell tumors (MGCTs) in adults, pediatric oncology collaborative groups still remain concerned about the late effects of cisplatin in children.
METHODS: We performed a literature search to identify randomized controlled trials (RCTs) that used carboplatin for MGCTs in adults. Since no RCTs were available in children, we identified cohort studies of pediatric MGCTs treated with carboplatin. We compared the adult and pediatric studies in terms of characteristics, doses of chemotherapy, and outcomes.
RESULTS: Of 2,131 publications retrieved, five RCTs in adults (1,340 patients) and four cohort studies in children (219 patients) met criteria for inclusion. All adult RCTs evaluated carboplatin versus cisplatin regimens in men with good-prognosis metastatic MGCTs. Carboplatin regimens had a higher risk of events (RR 2.51, P < 0.001) and of deaths (RR 2.21, P < 0.001) than cisplatin regimens. Across all five RCTs, 497/654 (76%) of adults who received carboplatin remained event-free. Compared to the adult trials, three pediatric studies used carboplatin at a higher dose, frequency, and number of cycles. Across these three studies, 158/179 (88%) of children remained event-free.
CONCLUSIONS: Cisplatin is superior to carboplatin at the studied doses for the treatment of adult metastatic MGCTs. However, we observe that carboplatin is associated with good outcomes for children with MGCT when used at the higher doses. We hypothesize that a risk-adapted approach utilizing both platinum agents may achieve the optimal balance between cure and late effects.

Related: Carboplatin

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