Extracranial Germ Cell Tumors Research Articles

Malignant extracranial germ cell tumors in the Netherlands between 1990 and 2018: Stable incidence and improved survival

BackgroundPopulation-based studies assessing long-term patterns of incidence and disease characteristics of germ cell tumors (GCTs) in children are scarce. We investigated incidence and survival trends of malignant extracranial GCTs in children using population-based nationwide data from the Netherlands. MethodsAll malignant extracranial GCTs diagnosed in patients aged 0–18 years between 1990 and 2018 were selected from the Netherlands Cancer Registry. Incidence rates were calculated as the average annual number of cases per 1 million person-years. Five-year overall survival (OS) was calculated. ResultsA total of 815 cases were identified. Gonadal GCTs (n=665, testis n=485, ovarian n=180) were more common than extragonadal GCTs (n=149). Stage distribution for testicular and extragonadal GCTs shifted between 1990 and 2004 and 2005–2018 towards more localized disease. The overall incidence remained stable over time, but a significant increase was noted for extragonadal GCTs in the 0–9 years age group. Survival of extragonadal GCTs (5-year OS 84.1%, 95% CI 77.1–89.1), in particular mediastinal GCTs (5-year OS 66.7%, 95% CI 45.7–81.1), was lower than that of gonadal GCTs (5-year OS testis 95.0%, 95% CI 92.7–96.7;ovary 97.8%, 95% CI 94.2–99.2). The 5-year OS of our entire cohort was 93.6% (95% CI 91.7–95.1). Five-year OS significantly increased from 89.5% (95% CI 86.1–92.2) in 1990–2004–97.4% (95% CI 95.3–98.5) in 2005–2018. ConclusionsAlthough the incidence of all malignant pediatric extracranial GCTs remained stable during 1990–2018, an increase was observed for extragonadal GCTs in younger children (0–9 years). There was a shift towards more localized disease for testicular and extragonadal GCTs. Five-year OS increased over time exceeding 90% (91.4%, 95% CI 82.7–95.8) in the most recent diagnostic period. Mediastinal GCTs had the lowest OS, supporting the need for future research.

Outcomes of pediatric extracranial germ cell tumors: A single center experience in a developing country.

The purpose of this study was to analyze the outcomes of extracranial GCT in children in a developing country and to assess prognostic factors. The data on 141 children (<18years old) with extracranial GCT, confirmed histopathologically, collected over the past 9years (from February 2013 to June 2022) were retrospectively studied. The patients underwent the same therapy with platinum-containing chemotherapy regimens. In the malignant GCT group, OS and EFS were 81.0 ± 4% and 73 ± 5%, respectively. OS and EFS in the teratoma group were 90 ± 5% and 85 ± 6%. In univariate analysis, parameters like stage of disease, tumor localization, AFP level ≥10,000ng/mL, serum AFP kinetics and resection status were found to be statistically significant prognostic factors. In the multivariate analysis, the significant adverse factors were the resection status, initial AFP level ≥10,000ng/mL and serum AFP kinetics slow down (p = .000). Good survival rates can be achieved in developing countries with adequate compliance with treatment protocols. The analysis demonstrates high efficacy of platinum-containing chemotherapy regimens. In our opinion, the protocol used in high-income countries can be implemented in low-income countries with the financial support from the government. The qualification of specialists is also important.

Diffusion-weighted imaging in pediatric extracranial germ cell tumors.

Germ cell tumors (GCTs) comprise a rare and heterogeneous group of neoplasms presenting different clinical and histological characteristics, leading to a challenging scenario in clinical practice. Diffusion-weighted imaging (DWI) has been suggested as an indirect marker of tumor density and cellularity and could be used to monitor therapeutic response. However, its role in pediatric GCTs needs to be clarified. Here, we evaluated the features of DWI in pediatric extracranial GCTs in a reference Brazilian institution. We included 43 pediatric patients with primary GCTs treated between 2008 and 2022 in Hospital de Amor de Barretos. The patients' MRI images included T1-weighted without contrast, T2-weighted, DWI and apparent diffusion coefficient (ADC) maps. DWI was evaluated in the section that exhibited the greatest restricted diffusion in the largest hypersignal area of the image. The lowest ADC value was determined to define the region of interest (ROI). We used a small ROI, avoiding necrotic, adipose tissue, noisy or nonenhancing lesion voxels as recommended. ROI determination was established by visual inspection by two radiologists in accordance. We used two values of b (b = 50 mm2/s or b = 800) for ADC values. The highest mean ADC (mADC) value was observed in pure teratomas (1,403.50 ± 161.76 x10-3 mm2/s; mean ± SD) compared to other histologies (yolk sac, mixed teratoma, dysgerminoma and mixed GCT) of GCT (p<0.001). Furthermore, ROC analysis determined a cutoff mADC value of 1,179.00 x 10-3 mm2/s that differentiated pure teratomas from the other GCT histologies with a sensitivity of 95.8% and a specificity of 92.9% (AUC = 0.979; p<0.01). A significant increase in mADC was observed for malignant GCTs in treatment (1,197.00 ± 372.00 mm2/s; p<0.001) compared to that exhibited at the time of diagnosis (780.00 ± 168.00 mm2/s; mean ± SD. Our findings suggest that mADC assessment could be used as a tool to distinguish pure teratomas from malignant CGT histologies at diagnosis. Additionally, we demonstrated reasonable evidence that it could be used as a complementary tool to monitor treatment response in patients with malignant GCT.

Extracranial Germ Cell Tumors in Children: Ten Years of Experience in Three Children's Medical Centers in Shanghai.

The aim was to describe the clinical features of extracranial germ cell tumors (GCTs) in pediatrics and study the clinical risk factors related to survival for malignant germ cell tumors (MGCTs) in order to optimize therapeutic options. The clinical data of children with extracranial GCTs in three children's medical centers in Shanghai were retrospectively analyzed. In total, 1007 cases of extracranial GCTs diagnosed between 2010 and 2019 were included in this study, including teratomas (TERs) 706 (70.11%) and MGCTs 301 (29.89%). There were twice as many TER cases as MGCT cases. Approximately 50% of children with GCTs were <3 years old (43.39% for TERs, 67.13% for MGCTs). GCTs in children of different ages show differences in tumor anatomical locations and pathological subtypes. The 5-year event-free survival (EFS) and overall survival (OS) of all patients with MGCTs were 82.33% (95% CI, 77.32%, 86.62%) and 94.13% (95% CI, 90.02%, 96.69%), respectively. The multivariate Cox regression analysis identified a primary site in the mediastinum and alpha fetoprotein (AFP) levels ≥10,000 ng/mL as independent adverse prognostic factors (p < 0.0.0001, χ2 = 23.6638, p = 0.0225, χ2 = 5.2072.). There were no significant differences in OS among children receiving various chemotherapy regimens, such as the BEP, PEB, JEB and other regimens (VBP/VIP and AVCP/IEV) (p < 0.05). The clinical features of GCTs in Chinese pediatrics are similar to those reported in children in Europe and America. The age distribution of pathological types and primary sites in GCTs reflect the developmental origin of type I and type II GCTs transformed from mismigration primordial germ cells (PGCs). Optimizing the current platinum-based chemotherapy regimens and exploring the treatment strategies for MGCTs of the mediastinum are future research directions.

Testicular cancer in 2023: Current status and recent progress.

Testicular germ cell tumor (GCT) is the most common solid tumor in adolescent and young adult men. Progress in the management of GCT has been made in the last 50 years, with a substantial improvement in cure rates for advanced disease, from 25% in the 1970s to nearly 80%. However, relapsed or platinum-refractory disease occurs in a proportion, 20% of whom will die from disease progression. This article reviews the current evidence-based treatments for extracranial GCT, the acute and chronic toxic effects that may result, and highlights contemporary advances and progress in the field.

Extracranial germ cell tumours: Mature and immature (1990-2015). First report by the South African Association of Paediatric Haematology Oncology (SAAPHO).

Outcomes of rare paediatric teratomas have not previously been reported nor treatment regimens standardised in low- and middle-income settings. We sought to evaluate treatment outcomes of children and adolescents with histologically confirmed extracranial germ cell tumours, both mature teratomas (MT) and immature teratomas (IT) in preparation for the development of the South African national treatment guideline. Retrospective data by folder review were collated from nine South African paediatric oncology units. Kaplan-Meier analysis with Cox regression was performed to determine 5-year overall survival (OS) and prognostic factors. From January 1990 to December 2015, 60 patients were diagnosed with MTs; 14 males (median age 2months; interquartile range [IQR]: 0-8.75months) and 46 females (median age 9months; IQR: 0-88.5months). Forty patients were diagnosed with ITs; 10 males (median age less than 1month; IQR: 0-1.75months) and 30 females (median age 4.5months; IQR: 1-162months). There were high rates of upfront surgical resections in patients with MTs (58/60; 96.6%) and ITs (36/40; 90%), and similarly satisfactory rates of complete resection in patients with both MTs (55/60; 91.7%) and ITs (32/40; 80%). The 5-year OS for the whole group was 85.4%, significantly influenced by stage: Stage I (96.9%), Stage II (100%), Stage III (38.9%) (p<.001 [MT]; p=.013 [IT]). The event-free survival (EFS) ratio for the whole cohort was 78.7%. Five-year OS for those with low-stage disease was excellent, but was poorer for patients with advanced disease. The implementation of a national treatment guideline will facilitate the standardising of surgical approaches, indications for chemotherapy and specifications for follow-up to improve survival and to collect more robust late effects data.

Children's Oncology Group's 2023 blueprint for research: Germ cell tumors.

Extracranial germ cell tumors (GCT) are a biologically diverse group of tumors occurring in children, adolescents, and young adults. The majority of patients have excellent outcomes, but treatment-related toxicities impact their quality of survivorship. A subset of patients succumbs to the disease. Current unmet needs include clarifying which patients can be safely observed after initial surgical resection, refinement of risk stratification to reduce chemotherapy burden in patients with standard-risk disease, and intensify therapy for patients with poor-risk disease. Furthermore, enhancing strategies for detection of minimal residual disease and early detection of relapse, particularly in serum tumor marker-negative histologies, is critical. Improving the understanding of the developmental and molecular origins of GCTs may facilitate discovery of novel targets. Future efforts should be directed toward assessing novel therapies in a biology-driven, biomarker-defined, histology-specific, risk-stratified patient population. Fragmentation of care between subspecialists restricts the unified study of these rare tumors. It is imperative that trials be conducted in collaboration with national and international cooperative groups, with harmonized data and biospecimen collection. Key priorities for the Children's Oncology Group (COG) GCT Committee include (a) better understanding the biology of GCTs, with a focus on molecular targets and mechanisms of treatment resistance; (b) strategic development of pediatric and young adult clinical trials; (c) understanding late effects of therapy and identifying individuals most at risk; and (d) prioritizing diversity, equity, and inclusion to reduce cancer health disparities and studying the impacts of social determinants of health on outcomes.

Integrated genomic analysis reveals aberrations in WNT signaling in germ cell tumors of childhood and adolescence

Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0–24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes. Significantly, we find that small molecule WNT inhibitors can suppress GCT cells both in vitro and in vivo. These results highlight the importance of WNT pathway signaling in GCTs across all ages and provide a foundation for future efforts to develop targeted therapies for these cancers.

Clinical and pathological characteristics of extra-cranial germ cell tumors: A 30-year single-center experience in Saudi Arabia.

To investigate the clinical and pathological characteristics of extracranial germ cell tumors (GCTs) in children aged 0-168 months treated at the National Guard Hospital, Jeddah, Saudi Arabia from 1990 to 2020. In this retrospective analysis, the data for all cases of GCTs were collected from 1990 to 2020. Statistical analyses were carried out using JMP software. The data was divided into 4 main categories: demographics, pathological/clinical features, recurrence, treatment and outcome. The study included 50 patients, with a mean age at diagnosis of 56.52 months. The median follow-up duration was 30 months. Most tumors were in the gonads, and among the extragonadal tumors, the sacro-coccyx was the most frequent site of the disease.The most common histological subtype of GCTs is yolk sac tumor, accounting for 28% of cases. Of the 50 patients, 46% received chemotherapy, and 54% underwent surgery without chemotherapy. Ten (20%) patients experienced recurrence after treatment. At the last follow-up, 96% of the patients were alive, and only 2 of the patients died due to advanced disease. Our findings were comparable to international data, but improvement in surveillance is required for long-term survivors.

Pediatric Extracranial Germ Cell Tumors: Review of Clinics and Perspectives in Application of Autologous Stem Cell Transplantation

Pediatric extracranial germ cell tumors (GCTs) are rare, accounting for approximately 3.5% of childhood cancers. Since the introduction of platinum-based chemotherapy, the survival rate of patients has improved to more than 80%. However, poor-risk subtypes of pediatric extracranial GCTs do not respond well to chemotherapy, leading to refractory or relapsed (R/R) diseases. For example, long-term survival rates of mediastinal GCTs or choriocarcinoma are less than 50%. According to reports in recent years for adult patients with R/R GCTs, the use of high-dose chemotherapy (HDCT) combined with autologous stem cell transplantation (ASCT) has clinical advantages; however, HDCT combined with ASCT has rarely been reported in pediatric GCTs. The R/R and poor-risk groups of pediatric GCTs could benefit from HDCT and ASCT.

High-dose chemotherapy with autologous stem cell transplantation for patients with extracranial germ cell tumors – experience of two Brazilian pediatric centers

Malignant extracranial germ cell tumors (GCTs) are rare in pediatric patients and are usually extremely sensitive to chemotherapy. Relapsed or refractory tumors, although rare, established the need for second-line therapies, including high-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT). However, there are few data on its use in children with GCTs. We present a retrospective analysis of all patients diagnosed with extracranial GCTs who received HDCT/ASCT at two Brazilian pediatric cancer centers from May 1999 to December 2019. We identified a total of 34 patients with a median age at diagnosis of 2.8 years (range, 0 to 18.8), who received HDCT/ASCT. Most patients (73%) received carboplatin, etoposide and melphalan (CEM) as a HDCT regimen. Fourteen patients received a second-line conventional dose chemotherapy (CDCT), 14 received a third-line CDCT and five received even a fourth-line CDCT prior to HDCT/ASCT. After a median follow-up of 22.7 months (range, 0.3 to 198.1), 16 patients had died after tumor relapse/progression and 2 patients died from HDCT/ASCT toxicity. We observed a 5-year OS of 47.1% and 5-year EFS of 44.1%. The 5-year OS for patients referred for HDCT/ASCT with progressive disease was 10% compared to 62.5% for those who achieved disease control before HDCT/ASCT (p = 0.001). In our experience, heavily pretreated children and adolescents with extracranial GCTs achieved considerable survival rates with HDCT/ASCT since, at least, partial control of their disease was possible before starting HDCT/ASCT. The role of HDCT/ASCT in pediatric patients with GCTs should be investigated in prospective trials.

Outcomes of relapsed/refractory extracranial germ cell tumors treated on conventional salvage chemotherapy without stem cell rescue: Experience from a tertiary cancer center.

Data on the outcome and prognostic indicators in extracranial relapsed/refractory germ cell tumors (rel/ref-GCTs) in children are limited to a few studies. This study looks at remission rates and outcomes of rel/ref-GCTs treated with conventional salvage chemotherapy (SC) regimens without stem cell rescue at a single center in the developing world. Patients treated at our center from January 2009 to December 2018 were included. Risk at primary presentation was stratified as all completely excised teratomas and stage I gonadal tumors being low risk (LR); stage IV ovarian, stage III-IV extragonadal GCTs as high risk (HR), and the remaining as intermediate risk (IR). SC regimens were: vinblastine-ifosfamide-cisplatin/carboplatin or paclitaxel-ifosfamide-cisplatin/carboplatin, or cisplatin/carboplatin-etoposide-bleomycin. Local therapy was either surgery and/or radiotherapy. The analyzable cohort comprised 50 patients (44 = rel-GCTs; 6 = ref-GCTs) with a median age of 3.8years and male:female ratio of 1.27:1. Primary location was ovary in 16 (32%), testicular in 10 (20%), and extragonadal in the rest (48%). Local, metastatic, and combined progression was noted in 28 (56%), 14 (28%), and eight (16%) patients, respectively, at a median time of 8.5months. At a median follow-up of 60months, the 5-year event-free survival (EFS) and overall survival (OS) of the entire cohort (n=50) were 42.4% and 50.0%, respectively. In patients previously exposed to platinum analogs (n=38), 5-year-EFS and OS were 27.7% and 31.7%, respectively. Local relapses did better when compared to metastatic and combined relapses (5-year EFS: 64% vs. 23% vs. 0%; p=.009). LR and IR tumors did better compared to HR (5-year EFS: 81.5% vs. 49.3% vs. 6.5%; p=.002). Patients with normalization of tumor markers after two cycles had a superior EFS (57.6% vs. 0%; p<.001). Relapsed tumors fared better than primary refractory GCTs (5-year EFS: 48.6% vs. 0%; p<.001). Primary refractory GCTs, extragonadal rel-GCTs, and rel/ref-GCTs with a poor biochemical response did poorly with conventional SC and need alternative treatment strategies. The rel/ref-testicular GCTs had the best chance of salvage despite a second recurrence (5-year EFS and OS: 28.60% and 42.90%, respectively).

Extracranial Germ Cell Tumor in Children: A Three-year Experience of Pediatric Hematology/Oncology Center, Medical City

Extracranial Germ Cell Tumor in Children: A Three-year Experience of Pediatric Hematology/Oncology Center, Medical City

Clinico-epidemiological profile and outcomes of extracranial germ cell tumours in paediatric age group in a tertiary care cancer centre in Northeast India

Clinico-epidemiological profile and outcomes of extracranial germ cell tumours in paediatric age group in a tertiary care cancer centre in Northeast India

Extracranial germ cell tumours in children and adolescents: Results from the French TGM13 protocol.

Chemotherapy for non-seminomatous germ cell tumours (NSGCT) exposes to dose-dependent toxicities. The TGM13-NS protocol (EudraCT 2013-004039-60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5-year event-free survival (EFS) at 80% or more. Patients less than 19years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate-risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine-bleomycin-cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10years) and four courses for IR2 (extragonadal tumour 10years or less) groups, and two high-risk (HR: metastatic and/or high TM) groups treated with etoposide-cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10years and low TM/testis tumour more than 10years and very low TM) groups and four courses for HR2 (remainder) groups. One hundred fifteen patients were included: median age of 12.8years (0.4-18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5-year EFS and overall survival (OS) were 87% (95% CI: 80-92) and 95% (89-98), respectively (median follow-up: 3.5years, range: 0.2-5.9), similar to those of the TGM95 protocol (5-year EFS 89% (84-93), 5-year OS 93% (89-95), p=.561). The 5-year EFS were 93% (95% CI: 80-98), 88% (71-95) and 79% (62-90) for ovarian, testicular and extragonadal tumours, respectively. The 5-year EFS varied (p=.02) according to the risk groups: 90% (66-97), 64% (30-85), 95% (72-99) and 87% (74-94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha-fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR=1.03 (1.003-1.007). Risk-adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy.

Radiotherapy within the interdisciplinary treatment strategy for pediatric extracranial germ cell tumors

<h3>Objectives</h3> Radiotherapy (RT) is not a standard modality in the treatment strategy for extracranial germ cell tumors (eGCT) of childhood due to the every young patient cohort and the risk to cause relevant late effects. However, it is used in individual cases to achieve local control. We want to evaluate the role of external beam radiotherapy for eGCT. <h3>Methods</h3> Recent protocols were systematically reviewed. Literature, results of the MAKEI-96 study and experiences from patients within the KiProReg study receiving proton irradiation (PT) were retrospectively evaluated for applied RT and tumor outcome. <h3>Results</h3> According to current protocols, RT is mainly considered for recurrent or residual disease after intensive multi-modal therapy. However, published data suggested that RT (≥ 45 Gy) seems to be beneficial to achieve local control (LC) [1]. Between 1983 and 2021, 41 patients (med. age 10.5 years; range, 0.1-18 years) were irradiated within the MAKEI-96-study or at our institution. Histological diagnoses were predominantly dysgerminomas and yolksac tumors at different sites. Patients were irradiated with various dose concepts applying total doses of 20-60 Gy and fraction doses of 1.5-4 Gy. PT was used in 14 out of the 41 patients. Follow-up time ranged from 1 to 147 months (mean: 58.8 months). During the observation period, LC was achieved in 32 of the 41 patients. <h3>Conclusion</h3> RT seems to be effective in achieving LC. Still, due to potential sequelae, RT has to be considered with caution and discussed individually by the multidisciplinary team, considering both risks and rewards. Strategies for standardized RT are lacking to allow prospective evaluation in near future.

Applications of the Grading Scales for the Detection of Ototoxicity in Children after Treatment of Neuroblastoma and Extracranial Germinal Tumor

Introduction: Advances in treatment have resulted in a significant increase in survival rates for patients cured of malignant diseases such as neuroblastoma (NBL) and extracranial germ cell tumor (GCT). NBL is one of the pediatric cancers during which potentially ototoxic cytostatic drugs (cisplatin and carboplatin) are used for treatment. Other cancers include germinal tumors, hepatoblastoma, sarcomas, and brain tumors. Often, this very aggressive treatment has a high risk of causing long-term side effects, including hearing loss. Hence, the present study aimed to evaluate the usefulness of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Brock, Chang, and International Society of Pediatric Oncology (SIOP) Boston scales in terms of detecting the high-frequency nature of hearing loss induced by ototoxic drugs and monitoring hearing status in children after completion of oncological treatment. Additionally, the frequency of hearing loss in children treated for NBL and extracranial GCT was assessed, and the principles of monitoring hearing in these patients were indicated. Methods: The study group consisted of 78 patients diagnosed with NBL (n = 47) and GCT (n = 31). There were 23 boys and 24 girls in the NBL group, aged 0–16 years, and 21 boys and 10 girls in the GCT group, aged 0–18 years. The control group consisted of 54 patients who had never received oncological treatment, were not taking potentially ototoxic drugs, and appeared socially efficient in the subjective audiological assessment. Audiometric examinations and DP-acoustic otoemission measurements were performed. Additionally, impedance audiometry tests were done to exclude a possible conductive component of the hearing loss. Results: The analysis shows that ototoxicity-induced hearing loss was observed in 13.8–65.5% of children. 75.9% of patients showed hearing loss in the 16 kHz frequency range, and at least 56.8% of patients showed hearing loss in the frequency range above 12.5 kHz. Hearing impairment, relevant to speech understanding, was displayed by more than 40% of children treated for NBL and GCT. Conclusions: The confirmation of hearing loss in nearly 65% of cases in both patients indicates the necessity to monitor the long-term side effects of anticancer treatment. Acoustic otoemission measurements, the adoption of articulatory indices based on an audiogram, or the use of arbitrary ototoxicity assessment scales such as Brock, Chang, or SIOP Boston are fully justified techniques for studying ototoxicity induced by cytostatic drugs. However, they all require continuous improvement to increase their sensitivity and specificity, especially in the pediatric group.

Pediatric Extracranial Germ Cell Tumors: Expression of microRNA.

Germ cell tumors (GCTs) may occur from the neonatal period to late adulthood, characterized by extensive clinical and pathologic heterogeneity. MicroRNAs are a family of small noncoding RNAs that regulate a wide array of biological processes including carcinogenesis. MicroRNAs may be used for many purposes in clinical diagnostics. Numerous studies have proven the diagnostic value of microRNA371-373 and microRNA302/367 expression in malignant GCT. The diagnostic value of microRNA375 is disputable, because while its value is confirmed by some research data, there are still others denying it. The results of our own research on the relative expression of 10 microRNAs, including microRNA375, associated with GCT in the tumor tissues of 84 children and adolescents are presented. In our research, overexpression of microRNA 371-373, 302/367 detected in the group of malignant GCT subtypes. Statistically significant expression of microRNA375 have been defined not only in the group of malignant GCT subtypes, but also in the group of immature teratomas. Among malignant GCTs, high expression of microRNA375 is specific for yolk sac tumors. In the group of seminomas, embryonic carcinomas, and mature teratomas expression of microRNA375 was observed imperceptible, even so the results were statistically insignificant. Expression of microRNA 371-373, 302/367 is representative of malignant GCT subtypes. Statistically significant and high expression of microRNA375 attributable for yolk sac tumors and immature teratomas.

Outcomes and prognostic variables of extracranial germ cell tumors in children and adolescents treated over a decade: A developing world perspective.

The purpose of this single-center study was to analyze the outcomes of extracranial germ cell tumors (GCTs) in children treated on a multimodality regimen. Retrospective study of children (<18years) with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10years (January 2009 to December 2018) treated on a uniform institution-based protocol consisting of both cisplatin- and carboplatin-based regimens. All completely excised teratomas and stage I gonadal tumors received no further therapy (low risk [LR]); stage IV ovarian, stage III-IV extragonadal GCTs received six cycles of chemotherapy (high risk [HR]), and the remaining received four cycles of chemotherapy (intermediate risk [IR]). A total of 297 children were treated with a female:male ratio of 1.72:1 and median age of 4years. Forty-three children had pure teratomas. Gonadal GCTs (N=180) were more common than extragonadal GCTs (N=117) with ovary as primary site in 128 children (43%) and sacrococcygeal site being the commonest extragonadal location (N=41; 14%). LR, IR, and HR disease were noted in 60 (20.2%), 125 (42%), and 112 (37.8%) patients, respectively. Three-fourths of ovarian tumors and half of testicular tumors operated prior to presentation needed upstaging. Forty-one patients relapsed and 43 children expired (disease-related: 33; toxic deaths: 9; unknown: 1). The 5-year event-free survival (EFS)/overall survival (OS) of malignant GCT (n=254) was 72.50%/82.70%, respectively, with gonadal site (p=.001), LR and IR (p=.001) and nonmetastatic disease (p=.001) being favorable prognostic variables. The LR and IR GCTs in our cohort had an excellent outcome. A significant proportion of IR gonadal GCTs can be spared of systemic chemotherapy by adhering to strict surgical guidelines. In HR GCTs however, intensifying therapies to improve outcomes must be balanced against the risk of cumulative toxicity, more so in a resource-limited setting.

Unilateral Cystic Teratoma of the Ovary in Children: A Case Report

Teratoma is a type of extracranial germ cell tumor that often occurs and correlates with age and anatomical location. Mature Cystic Teratoma (MCT) is the most common ovarian tumor in children and adolescents. The most common sites for teratomas are the sacrococcygeal region and the ovaries. Laparoscopy is by far the surgical treatment of choice for teratomas. We report a case of a 9-year-old girl with a chief complaint of left lower quadrant abdominal pain 1 week before hospital admission. The patient appears weak and has decreased appetite, accompanied by weight loss, and painful urination. Physical examination of abdominal distension (+), tenderness, and release in the left lower quadrant (+). The patient had not menstruated, and a history of vaginal discharge was denied. On MSCT-scan examination of the abdomen with contrast, a cystic mass was found that adhered to and pushed the surrounding bowel structures in the lower abdominal region. On histopathological examination taken from the left ovary preparation, a macroscopic examination found cyst tissue of 9.5 x 6.5 x 5 cm. The cyst is gray-black, filled with blood and a white pulp mass with hair. On microscopic examination found cysts with fibrous connective tissue stroma containing vascular. The treatment is in the form of laparoscopy and after surgery, currently, the patient is in good condition and will be followed up again every 3 months.