Management of differences of sex development (DSD) continues to evolve, with increased attention to fertility. Knowledge gaps remain among providers and patients about fertility potential and options for fertility preservation. It is complicated, requiring individualized assessment. Fertility potential varies by diagnosis, gonadal status and age. Many DSD conditions confer increased risk of gonadal germ cell tumor, prompting consideration of prophylactic gonadectomy and loss of potential germ cells or gametes. These potential gametes also may not match the sex designation or gender identity. Some causes of DSD are heritable, thus genetic counseling is important to address inheritance risks. Fertility considerations are further complicated by the need for some management decisions to occur during the pediatric period, an individual may not be able to assent or consent, and decisions may be made by parents. Advances in ART and fertility preservation techniques have improved outcomes, and investigational techniques may offer more future options.

To evaluate the role of carboplatin-based chemotherapy in patients diagnosed with malignant gonadal germ cell tumors (GCTs), we conducted a systematic review and meta-analysis. We searched PubMed, MEDLINE, Embase, Cochrane library, and Web of Science. Randomized controlled trials or cohort studies on gonadal GCTs between January 1, 1970 and April 26, 2023 were enrolled. The treatment failure rate and mortality rate were the primary outcomes. Subgroup analysis based on the primary tumor site and dose of carboplatin was also conducted. In total, 8 studies with 1,409 patients were included. Compared to cisplatin-based chemotherapy, carboplatin-based chemotherapy had an increased treatment failure rate (odds ratio [OR]=2.23; 95% confidence interval [CI]=1.61-3.08; p<0.001), but similar overall survival outcomes (OR=1.68; 95% CI=0.61-4.61; p=0.315). Subgroup analysis revealed that carboplatin-based chemotherapy did not increase the risk of treatment failure and death in ovarian GCT, while a higher risk of treatment failure and a similar risk of death were observed in testicular GCT. Patients treated with high-dose carboplatin calculated 400 or 600 mg/m² (area under the curve=7.9) obtained similar failure-free survival to the cisplatin group (OR=0.84; 95% CI=0.40-1.73; p=0.629). Compared to the cisplatin group, milder nausea and vomiting, nephrotoxicity, ototoxicity, and more severe myelosuppression were observed in the carboplatin group. In conclusion, carboplatin-based chemotherapy achieves a comparable overall survival outcome to cisplatin-based chemotherapy in gonadal GCT patients, suggesting that carboplatin is a candidate substitute for cisplatin. The efficacy of carboplatin is dose-dependent. High-dose carboplatin can obtain better therapeutic effects with more tolerable toxicities than cisplatin.

Primary mediastinal germ cell tumor (MGCT) is an uncommon tumor. Although it has histology similar to that of gonadal germ cell tumor (GCT), the prognosis for MGCT is generally worse than that for gonadal GCT. We performed visual assessment and quantitative analysis of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) for MGCTs. A total of 35 MGCT patients (age = 33.1 ± 16.8 years, F:M = 16:19) who underwent preoperative PET/CT were retrospectively reviewed. The pathologic diagnosis of MGCTs identified 24 mature teratomas, 4 seminomas, 5 yolk sac tumors, and 2 mixed germ cell tumors. Visual assessment was performed by categorizing the uptake intensity, distribution, and contour of primary MGCTs. Quantitative parameters including the maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter were compared between benign and malignant MGCTs. On visual assessment, the uptake intensity was the only significant parameter for differentiating between benign and malignant MGCTs (p = 0.040). In quantitative analysis, the SUVmax (p < 0.001), TBR (p < 0.001), MTV (p = 0.033), and TLG (p < 0.001) showed significantly higher values for malignant MGCTs compared with benign MGCTs. In receiver operating characteristic (ROC) curve analysis of these quantitative parameters, the SUVmax had the highest area under the curve (AUC) (AUC = 0.947, p < 0.001). Furthermore, the SUVmax could differentiate between seminomas and nonseminomatous germ cell tumors (p = 0.042) and reflect serum alpha fetoprotein (AFP) levels (p = 0.012). The visual uptake intensity and SUVmax on [18F]FDG PET/CT showed discriminative ability for benign and malignant MGCTs. Moreover, the SUVmax may associate with AFP levels.

The incidence of extra-gonadal germ cell tumor is low. There are few reports about liver metastasis and multiple systemic metastasis of mediastinal germ cell tumor. Here, we report a case of a 42-year-old young man with mediastinal mass discovered by computed tomography, which was finally confirmed as mediastinal germ cell tumor after many pathological biopsies. After radiotherapy and chemotherapy, the mediastinal mass was stable, but a new mass appeared in the liver. Mediastinal mass remained stable after modification of treatment regimen, but multiple metastases were found throughout the body. He finally died after 8 months of treatment because of his poor health.

Mediastinal seminomas arise due to abnormal migration of the totipotent stem cells during development. They occur very occasionally and makes up about 0.5-5 % of all mediastinal tumors. These usually occur in middle aged men, between 20 and 40 years. In pediatric age group, it is considered as an extremely rare finding, accounting for 3 %-7 % of all primary germ cell tumors. We report a rare case of a 16-year-old boy with biopsy proven seminomatous type of germ cell tumor in anterior mediastinum who presented with productive cough and progressive dyspnea. The occurrence of mediastinal seminoma especially in pediatric population is a very infrequent finding, hence, very little literature is found in this regard as per our knowledge. The incidence of primary mediastinal germ cell tumors is approximately around 3 %-6 % of all the germ cell tumors in pediatric population. Diagnosis of mediastinal seminomas need a multipronged approach and treatment is associated with multidisciplinary procedures including chemotherapy combined with subsequent surgical resection for long term survival benefits. From the above presented case, it can be safely concluded that multimodality treatment approach of chemotherapy combined with surgical resection could ensure long-term survival benefits in extra-gonadal mediastinal seminomas.