Germ Cell Tumors In Children Research Articles

GCT-56 - Principles of surgical treatment for germ cell tumours in children

GCT-56 - Principles of surgical treatment for germ cell tumours in children

Progress in diagnosis and treatment of intracranial germ cell tumors in children

Intracranial germ cell tumors(icGCTs)are rare extragonadal neoplasms that mostly occur in children.It is insidious, and its clinical manifestations are diverse according to the location, size of tumors and sex.It often has symptoms of diabetes insipidus, precocious puberty and other hypopituitarism in early stage.A few patients have neuropsychiatric symptoms such as hemiplegia and visual impairment.Diagnosis is mainly based on clinical manifestations, tumor markers, brain imaging, reactivity to experimental radiotherapy and pathological biopsy.Treatment is mainly a combination of radiotherapy and chemotherapy.Postoperatively, multiple pituitary hormone deficiency is common, and life-long hormone replacement therapy is adopted to ensure growth and development of the children.This article reviews the early diagnosis and treatment of intracranial germ cell tumors. Key words: Intracranial germ cell tumor; Human chorionic gonadotropin; Hormone replacement therapy

Results from the UK Children's Cancer and Leukaemia Group study of extracranial germ cell tumours in children and adolescents (GCIII)

BackgroundFor extracranial malignant germ cell tumours (MGCTs) in the UK, the GCII study used carboplatin-based chemotherapy (JEb) and demonstrated equivalent survival to cisplatin-containing protocols. GCIII, a single-arm observational study, used new risk stratification, replaced consolidation chemotherapy with a standard number of cycles and introduced surveillance for all stage I MGCTs. Pure teratomas were registered to understand their natural history. MethodsPatients with MGCTs were stratified to three risk groups – low risk (LR), intermediate risk (IR) and high risk (HR), using stage and prognostic factors. Patients with alpha fetoprotein (AFP) >10,000 kU/L, stage IV disease (except testis <5 years and all germinomas) or stage II-IV mediastinal tumour were classified HR. Stage I tumours (LR) received chemotherapy only if disease progressed. IR and HR patients received 4 and 6 JEB cycles, respectively. Carboplatin dose was calculated using glomerular filtration rate to give an area under the curve of 7.9 ml/m2.min. ResultsEighty-six patients with MGCTs were enrolled from 2005 to 2009: 59% female, median age, 5.7 years. Twenty-five patients were LR, 21 IR and 38 HR. Seven LR patients had disease progression; all were successfully treated with chemotherapy. Overall survival (OS) for the whole group was 97%; 5-year event-free survival for JEb-treated patients was 92%, and OS, 95%. JEb was well tolerated with no observed significant hearing or renal side-effects. There was no discernible difference in carboplatin dose whether calculated by body surface area or creatinine clearance. Forty-seven patients with teratoma were managed with surgery and one had malignant transformation. ConclusionCarboplatin-based chemotherapy as part of a risk-stratified approach leads to excellent survival in paediatric MGCTs, minimising potential burden of long-term effects.

Prenatal Exposure to Air Toxics and Malignant Germ Cell Tumors in Young Children.

To assess prenatal air toxics exposure and risk for childhood germ cell tumors (GCTs) by histological subtype (yolk sac tumor and teratoma). In this case-control study, GCT cases less than 6 years (n = 243) identified from California Cancer Registry records were matched by birth year to cancer-free population controls (n = 147,100), 1984 to 2013. Routinely monitored air toxic exposures were linked to subjects' birth address. Logistic regression estimated GCT risks per interquartile range increase in exposure. Prenatal exposure to various highly-correlated, traffic-related air toxics during the second trimester increased GCT risk, particularly 1,3-butadiene (odds ratio [OR] = 1.51; 95% confidence interval [CI] = 1.01, 2.26) and meta/para-xylene (OR = 1.56; 95% CI = 1.10, 2.21). Analyses by subtype indicated elevated ORs for yolk sac tumors but not teratomas. Our estimated ORs are consistent with positive associations between some prenatal traffic-related air toxics and GCT risk, notably yolk sac tumors.

Clinical experience of craniospinal intensity-modulated spot-scanning proton therapy using large fields for central nervous system medulloblastomas and germ cell tumors in children, adolescents, and young adults.

The outcomes of intensity-modulated proton craniospinal irradiation (ipCSI) are unclear. We evaluated the clinical benefit of our newly developed ipCSI system that incorporates two gantry-mounted orthogonal online X-ray imagers with a robotic six-degrees-of-freedom patient table. Nine patients (7–19 years old) were treated with ipCSI. The prescribed dose for CSI ranged from 23.4 to 36.0 Gy (relative biological effectiveness) in 13–20 fractions. Four adolescent and young adult (AYA) patients (15 years or older) were treated with vertebral-body-sparing ipCSI (VBSipCSI). Myelosuppression following VBSipCSI was compared with that of eight AYA patients treated with photon CSI at the same institution previously. The mean homogeneity index (HI) in the nine patients was 0.056 (95% confidence interval: 0.044–0.068). The mean time from the start to the end of all beam delivery was 37 min 39 s ± 2 min 24 s (minimum to maximum: 22 min 49 s – 42 min 51 s). The nadir white blood cell, hemoglobin, and platelet levels during the 4 weeks following the end of the CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0071, 0.0453, 0.0024, respectively). The levels at 4 weeks after the end of CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0023, 0.0414, 0.0061). Image-guided ipCSI was deliverable in a reasonable time with sufficient HI. Using VBSipCSI, AYA patients experienced a lower incidence of serious acute hematological toxicity than AYA patients treated with photon CSI.

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.

Герминогенные опухоли у детей: 20-летний опыт лечения в НМИЦ онкологии им. Н.Н. Петрова

Герминогенные опухоли у детей: 20-летний опыт лечения в НМИЦ онкологии им. Н.Н. Петрова

Delays in Diagnosis of Pediatric Histologically Confirmed Sellar Germ Cell Tumors in China: A Retrospective Risk Factor Analysis

Sellar germ cell tumors (GCTs) occur more frequently in childhood. Some will present as malignancy with infiltration and metastasis. However, the association between the timeliness of diagnosis and outcome has been controversial. We investigated the clinical risk factors associated with a diagnostic delay in patients with sellar GCTs in China. The data from 53 patients aged <18 years with histologically confirmed sellar GCTs at Peking Union Medical College Hospital treated from January 2008 to December 2016 were reviewed retrospectively. The median interval between symptom onset and diagnosis was 25 months. Of the 53 patients, 44 (83%) had a delayed diagnosis. Most patients (86%) with a delayed diagnosis presented with polyuria or polydipsia. Of the 53 patients, 48 (91%) exhibited changes in the pituitary stalk. Patients with a germinoma (odds ratio, 4.1; 95% confidence interval, 2.4-6.9) and slow growth (odds ratio, 5.3; 95% confidence interval, 1.2-24.5) were more likely to have a delayed diagnosis. The overwhelming majority of patients with a delayed diagnosis (96%) had been seen by >1 doctor. No statistically significant differences were found in the mean survival time (P= 0.21) or mean progression-free survival time (P= 0.36) between patients with and without delay in diagnosis, respectively. A significant proportion of patients with sellar GCTs will experience a delay in the time to diagnosis. Although a delay in diagnosis did not reduce the survival time or progression-free survival time for patients with sellar GCTs, it might increase the risk of short stature. Thus, a detailed medical history and an immediate radiological examination are important for the early diagnosis of sellar GCTs in childhood.

Germ cell tumours in children and adolescents

Germ cell tumours in children and adolescents

Malignant sacrococcygeal germ cell tumors in children: a 30-year experience from a single institution.

Our aim was to analyze treatment results and survival characteristics of our patients with malignant sacrococcygeal germ cell tumors. Patient files of children with malignant sacrococcygeal germ cell tumors, treated at our institution between 1979 and 2009, were searched. Patient characteristics, histopathological subtypes, extension of disease, alpha-fetoprotein (AFP) level at the time of diagnosis and relapse, extent of surgical resection, chemotherapy protocols, details of radiotherapy and survival characteristics were recorded. A total of 58 patients (M/F = 20/38) with malignant sacrococcygeal germ cell tumor was included in analysis. With a mean follow-up of 156 months (range, 26 days to 288.8 months) overall and event-free survival rates of the 58 patients were 50.9% and 43.8%, respectively. AFP status of the patients (37% in patients with <10,000 ng/ml, 68.9% in patients with ≥ 10,000 ng/ml), type of resection (total vs others), coccygeal resection, chemotherapy protocol (PEB vs others) and number of chemotherapy courses had an impact on event-free survival in univariate analysis. In multivariate analysis, AFP status had the greatest effect on prognosis. Our treatment results are worse than those reported in the literature. Elevated AFP level at the time of diagnosis had a beneficial effect on prognosis, but year of diagnosis, tumor stage, presence of metastasis, tumor size and histopathological subtype had no impact on survival in patients with malignant sacrococcygeal germ cell tumors.

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.

Advanced surgical strategy for giant mediastinal germ cell tumor in children

Giant mediastinal germ cell tumor (MGCT) requires a well-planned advanced surgical approach. We retrospectively reviewed our surgical strategy for giant MGCT. Five children (median age, 5 years) with giant MGCT were treated in our institute from 2012 to 2016. The initial diagnosis was made by tumor markers and image inspection in all cases. Benign teratomas (2 girls) and malignancies (3 boys) were treated with upfront surgery and radical tumorectomy after neo-adjuvant chemotherapy, respectively. After detailed 3D-CT, radical tumor excision was performed supported by a skilled pediatric cardiovascular surgeon. The basic approach was as follows: under cardiopulmonary support (CPS) or with CPS on standby, via median sternotomy, the pericardium and phrenic nerve were resected en bloc with the tumor, followed by diaphragmatic plication. Open biopsy was performed via lateral thoracotomy in 1 patient who showed dense adhesion and fistula formation in the lung; lobectomy via hemi-clamshell incision was required. No deaths or severe sequelae occurred in this series. Resectability is the most important predictor of outcomes for MGCTs. Preoperative 3D-CT and CPS can enable complete resection and ensure surgical safety. Well-functioned surgical team is critical success factor in such advanced surgery.

Exposure to ambient dichloromethane in pregnancy and infancy from industrial sources and childhood cancers in California.

The incidence of childhood cancers has been increasing and environmental exposure to air toxics has been suggested as a possible risk factor. This study aims to explore ambient exposure to dichloromethane (methylene chloride). We frequency matched by birth year approximately 20 cancer-free controls identified from birth records to all childhood cancers ages 0-5 in the California Cancer Registry diagnosed from 1988 to 2012; i.e. 13,636 cases and a total of 270,673 controls. Information on industrial releases of dichloromethane within 3km of birth addresses was retrieved from mandatory industry reports to the EPA's Toxics Release Inventory (TRI). We derived exposure to dichloromethane within close vicinity of birth residences using several modeling techniques including unconditional logistic regression models with multiple buffer distances, inverse distance weighting, and quadratic decay models. We observed elevated risks for germ cell tumors [Odds Ratio (OR): 1.52, 95% Confidence Interval (CI) 1.11, 2.08], particularly teratomas (OR: 2.08, 95% CI 1.38-3.13), and possible increased risk for acute myeloid leukemias (AML) (OR: 1.64, 95% CI 1.15-2.32 in the quadratic decay model). Risk estimates were similar in magnitude whether releases occurred in pregnancy or the child's first year of life. Our findings suggest that exposure to industrial dichloromethane releases may be a risk factor for childhood germ cell tumors, teratomas, and possibly AML.

Gonadal germ cell tumors in children: A retrospective review of a 10-year single-center experience.

Background:The true incidence of gonadal germ cell tumors (GCTs) in children is unknown. Few studies have been published concerning about pediatric gonadal GCTs. The aim of this study is to review and analyze clinical data on the diagnosis and management of gonadal GCTs in children.Methods:Between 2005 and 2015, 127 pediatric patients (<14 years old) with gonadal GCTs admitted to our institute were reviewed. Clinical features, imaging and laboratory studies, surgical approaches, as well as pathological diagnoses were recorded.Results:The series comprised 53 males with testicular GCTs and 74 females with ovarian GCTs. Their median age was 5.8 years old. Palpable mass was the main clinical manifestation of testicular GCTs, while abdominal pain and abdominal distention were the most frequent presenting symptoms of ovarian GCTs. Both computed tomography and magnetic resonance imaging showed a high diagnostic yield. AFP levels were elevated in most malignant GCTs, markedly elevated in yolk sac tumors. All patients were treated surgically. Mature teratoma was the most common type of benign GCTs, while yolk sac tumor was the most common type of malignant GCTs.Conclusion:Gonadal GCTs in children have various of pathological types, as well as clinical manifestations. Imaging and laboratory data could be useful for differentiation of malignant from benign tumors. Final diagnosis depends on pathology. Surgical excision of the gonadal GCTs is the prior option.

Risk of second malignant neoplasms in women and girls with germ cell tumors

While an elevated risk of second malignant neoplasms (SMNs) has been observed in men treated for germ cell tumors (GCTs), risk of SMNs have not been quantified in adult women or in girls treated for GCTs. One-year survivors of primary GCTs diagnosed between January 1980 and December 2012 were identified from Surveillance, Epidemiology, and End Results (SEER 9) registries. Risk of SMNs was calculated using SEER*Stat. Among 1507 patients, a total of 47 SMNs were identified. The overall risk of SMNs was not elevated in females overall or in females treated for GCT during adulthood although SMN sites (pancreas, soft tissue, bladder, kidney, and thyroid) and trends were comparable with those in men. There were too few childhood GCT cases with SMNs for further analysis. Unlike men, women treated for GCTs did not have a statistically significant elevated risk of SMNs [standardized incidence ratio = 1.11; 95% confidence interval (CI) = 0.81-1.47]. The fact that SMNs in women occur in sites similar to those observed in men indicate that long-term follow-up of a larger cohort of females treated for GCT is warranted.

Excision of retroperitoneal germ cell tumor in children: A distinct surgical challenge

PurposeThe excision of retroperitoneal germ cell tumor (GCT) is a surgical challenge compounded by the absence of definite surgical guidelines. The aim of this study is to present the surgical difficulties and morbidity associated with resection of these tumors. MethodsFifteen patients (7 males and 8 females) undergoing excision of retroperitoneal GCT between February 2008 and February 2016 were evaluated. ResultsExcept for an adolescent, the majority of patients were infants (median age: 4months). The surgical excision entailed extensive vascular dissection in all patients with associated significant blood loss in two, adjacent organ removal in five, and vessel repair in one patient. The resection was complete in all except two patients. Both the patients with incomplete resections had immature teratoma and received postoperative chemotherapy. At a median follow-up of 53months, 13 patients are alive and disease free, one patient is alive with stable disease, and one patient had died owing to respiratory complications. There were no local recurrences in the patients with complete excision. ConclusionAlthough the outcomes are excellent after surgery, resection of retroperitoneal GCT is a distinct surgical challenge. The surgical difficulties emanate from the need for extensive vascular dissection and risk to adjacent structures. Level IV evidenceTherapeutic study.

A rare case of ovarian dysgerminoma in a 6-year old child in Lagos: A case report

Dysgerminoma is the most common malignant germ cell tumor in children and adolescents. Most cases occur in the 2 nd and 3 rd decades of life, but 10% of cases occur in the 1 st decade of life. The rarity of this malignancy in prepubertal children and the recognized controversies in its management prompted this case report. The case of a 6‑year‑old girl who had laparotomy and unilateral adnexectomy with subsequent histological diagnosis of an ovarian dysgerminoma was presented. Prognosis depends on the stage of the tumor at presentation, and conservative surgery should be the aim during the initial treatment. Adoption of multidisciplinary management within an oncology board with joint decision on the need for adjuvant chemotherapy for early stage diseases will confer good prognosis. Keywords: Germ cell tumor; malignant; management; multidisciplinary

Unusual association of testicular yolk sac tumor with pectus excavatum in an 18-month-old child: A case report

Testicular tumors are rare in children, but highly treatable and usually curable. In children, testicular tumor accounts for ~ 1–2% of all tumors. Among testicular tumors, germ cell tumors have a bimodal age distribution. One peak occurs in the first 2 years of life and the second peak occurs in young adults 15–35 years of age. Germ cell tumors in children are distinct from that in adults in term of their behavior, histological nature, metastasis, and the treatment needed. Here, we present a case of testicular tumor with a chest wall deformity in an 18-month-old male child. This is the first case of testicular yolk sac tumor in an 18-month-old male child with chest wall deformity (pectus excavatum).

Risk of malignant childhood germ cell tumors in relation to demographic, gestational, and perinatal characteristics

BackgroundChildhood germ cell tumors (GCTs) are a rare assortment of neoplasms, with mostly unknown etiology, that are believed to originate very early in life. Few studies have examined risk factors by histologic subtype, despite evidence of different risk profiles. Materials and methodsIn this population-based case-control study, 451 childhood malignant GCT cases ages 0–5 years were identified from the California Cancer Registry. Differentiating between common histologic subtypes, we identified 181 yolk sac tumors, 216 teratomas, and 54 rarer subtypes. Cases were linked to their birth certificates and 271,381 controls, frequency matched by birth year, were randomly selected from California birthrolls to investigate the contributions of demographic, gestational, and pregnancy factors using unconditional logistic regression analysis. ResultsCompared to non-Hispanic whites, Asian/Pacific Islander children were at an increased risk for developing GCTs (odds ratio [OR]=1.94; 95% confidence interval [CI]=1.47, 2.56). Among pregnancy complications and procedures, yolk sac tumors were positively associated with the presence of fetopelvic disproportion (OR=2.97; 95% CI=1.55, 5.68), while teratomas were strongly associated with polyhydramnios or oligohydramnios (OR=14.76; 95% CI=7.21, 30.19) and the presence of an ear, face, or neck anomaly at birth (OR=93.70; 95% CI=42.14, 208.82). ConclusionsMalignant yolk sac tumors and malignant teratomas exhibited distinct demographic and gestational characteristics; additionally, complications in pregnancy and labor may be brought on by specific histologic subtypes.

Testicular germ cell tumors (TGCTs) in neonates and infants.

Dr. Louis Dehner has contributed significantly to our understanding of testicular germ cell tumors in children. This review article considers the molecular biology, clinical attributes, pathologic findings, and prognosis of those lesions.