Rupture and hemorrhage of a seminoma mixed with yolk sac tumors in 46XY partial gonadal dysgenesis: a case report and literature review

Background 46XY partial gonadal dysgenesis (PGD) is a rare subtype of disorder of sex development (DSD). 46YY PGD is a congenital disease with atypical chromosomal, gonadal, or anatomical sex development. The patient in this case report had male and female genitalia simultaneously. We created a flowchart of the differential diagnosis for clinicians. Case presentation A 41-year-old male was admitted to the hospital complaining of lower quadrant abdominal pain for 1 day. Physical examination revealed that his penis size was normal, but a urethral orifice was located in the perineum area between the scrotum and anus. One small testicle was in the left scrotum, but no testicle was present on the right. The patient’s abdomen was bulging, and he had lower abdominal pain. According to the emergency CT scan, a lesion (74*65 mm) was found in the right pelvis between the bladder and rectum. The lesion showed an unclear boundary and hematocele appearance. The lesion was removed by emergency surgery, and the pathology report indicated a mixed germ cell tumor with a seminoma and yolk sac tumors. Conclusion This article is a case report of germ cell tumors in 46XY PGD patients. The literature review summarizes the clinical diagnosis, and a flowchart is provided for physicians in future practice. The importance of this report is that it will help acquaint physicians with this rare disease and make the right initial clinical decision quickly through the use of this flowchart. However, the variants of special subtypes of 46XY DSD are myriad, and all the diagnoses could not be covered in one flowchart.

Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance

Yolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. We show that microsatellite instability status and mutational signatures are informative of chemoresistance. We identify somatic driver candidates, including significantly mutated genes KRAS and KIT and copy-number alteration drivers, including deleted ARID1A and PARK2, and amplified ZNF217, CDKN1B, and KRAS. YSTs have very infrequent TP53 mutations, whereas the tumors from patients with abnormal gonadal development contain both KRAS and TP53 mutations. We further reveal a role of OVOL2 overexpression in YST resistance to cisplatin. This study lays a critical foundation for understanding key molecular aberrations in YSTs and developing related therapeutic strategies.

Case Report: Extragonadal Yolk Sac Tumors Originating From the Endometrium and the Broad Ligament: A Case Series and Literature Review

Yolk sac tumors (YSTs) of the endometrium and the broad ligament are very rare, with only 29 cases and one case of each other reported before in the English literature. Due to lack of standard guidelines, the treatment strategies of these diseases are controversial. Here, we share two cases of YSTs originating from the endometrium and the broad ligament respectively and review related literature. A 35-year-old woman was diagnosed with endometrial YST in our center and underwent surgery followed by chemotherapy with BEP (bleomycin, cisplatin and etoposide) regimen for six courses. After follow-up for 21 months, there is still no evidence of relapse. Another 36-year-old woman was admitted to our department with YST of the broad ligament. She was treated with surgery followed by chemotherapy with BEP regimen and was lost to follow-up after completing therapy. The case of endometrial YST we shared was similar to cases reported before, while the case with YST of the broad ligament we shared was the second case reported worldwide. Both of these two cases were treated with surgery combined with chemotherapy with BEP regimen.

Surveillance alone in stage I malignant ovarian germ cell tumors: a MITO (Multicenter Italian Trials in Ovarian cancer) prospective observational study

ObjectiveThe aim of this study was to analyze the oncological outcome of stage I malignant ovarian germ cell tumors patients included in the MITO-9 study to identify those who might be recommended routine surveillance alone after complete surgical staging.MethodsMITO-9 was a prospective observational study analyzing data collected between January 2013 and December 2019. Three groups were identified: group A included 13 patients stage IA dysgerminoma and IAG1 immature teratoma; group B included 29 patients with stage IB–C dysgerminomas, IA–C G2–G3 immature teratomas and stage IA mixed malignant ovarian germ cell tumors and yolk sac tumors; and group C included five patients (two patients with stage IC1 and one patient with stage IC2 yolk sac tumors and two patients with mixed-stage IC2 malignant ovarian germ cell tumors).ResultsA total of 47 patients with stage I conservatively treated malignant ovarian germ cell tumors were analyzed. Two patients in group B were excluded from the routine surveillance alone group due to positive surgical restaging. Therefore, a total of 45 patients were included in the study. Median follow-up was 46.2 months (range; 6–83). In total, 14 of 45 patients (31.1%) received chemotherapy, while 31 (68.9%%) underwent surveillance alone. One patient in group A, with stage IA dysgerminoma had a relapse, successfully managed with conservative surgery and chemotherapy. None of the patients in group B and C relapsed. All patients were alive at completion of the study. Overall, among 31 patients (68.9%) who underwent surveillance alone, only one patient relapsed but was treated successfully.ConclusionsOur data showed that close surveillance alone could be an alternative option to avoid adjuvant chemotherapy in properly staged IB–C dysgerminomas, IA–IC G2–G3 immature teratomas, and IA mixed malignant ovarian germ cell tumors with yolk sac tumor component.

Parental occupation and childhood germ cell tumors: a case–control study in Denmark, 1968–2016

Purpose To examine associations between parental occupation and childhood germ cell tumors (GCTs) in offspring while distinguishing by common histologic subtype (i.e., yolk sac tumor and teratoma). Methods This population-based case–control study included childhood GCT cases in Denmark diagnosed 1968–2015 (< 16 years old at diagnosis) and sex and birth year-matched controls. Demographic information and parental employment histories were obtained from Danish registries. Parental occupation was assessed by industry; job-exposure matrices were used to examine specific occupational exposures (i.e., potentially carcinogenic organic solvents and social contact). Conditional multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Results Overall, 178 childhood GCT cases (50 yolk sac tumors; 65 teratomas) and 4,355 controls were included for analysis. Maternal employment in education during pregnancy was associated with offspring GCTs (OR 2.45, 95% CI 1.23–4.90), especially yolk sac tumors (OR 5.27, 95% CI 1.94–14.28). High levels of both maternal and paternal occupational social contact were also associated with offspring yolk sac tumors across all exposure periods (ORs 2.30–4.63). No signals were observed for paternal occupational solvent exposure, while imprecise associations were estimated for maternal exposure (e.g., dichloromethane exposure during pregnancy, OR 1.51, 95% CI 0.77–2.95). Conclusion Our findings suggest that parental occupation is associated with offspring GCTs, with most consistent evidence supporting an association between maternal employment in education or other high social contact jobs and offspring yolk sac tumors.

Management of Primary Mediastinal Yolk Sac Tumors: A Single Institution Experience with 10 Patients

Background: Primary mediastinal yolk sac tumors is a kind of primary mediastinal non-seminomatous germ cell tumor . The current treatment strategies in primary mediastinal non-seminomatous germ cell tumor is neoadjuvant chemotherapy followed by residual mass surgical resection . We reviewed our institutional 5 years' experience with Primary mediastinal yolk sac tumors who treated with platinum-based neoadjuvant chemotherapy and extended resection.Methods： We experienced 10 cases of Primary mediastinal yolk sac tumors from October of 2014 to October of 2019. 7 patients received preoperative platinum-based chemotherapy followed by surgical resection of residual mediastinal mass. The other 3 patients were received initial surgical resection without preoperative chemotherapy.Results：R0 resection was achieved in 8 patients (80%), and R2 resection was in the other 2 patients (20%). All the 7 patients with neoadjuvant chemotherapy were R0 resections, however all of them had viable tumor in their surgical specimen. Morbidities after surgery occurred in 2 patients, including 2 pneumonias ,1 type I respiratory failure and 1 acute left heart failure, and They were died within 2 months after surgery. At the time of writing ,3 patients are alive without evidence of disease,7 patients died , of which 5 patients have died of tumor-related causes and 2 died of postoperative complications. 8 patients were included in the follow-up. Among them 7patients experienced progressed within one year. 8 patients were included in the follow-up,mPFS and mOS in 8 patients were 3.7 months (2.6-41.3m) and 23.15 months (8.6-41.3m) , respectively. The 7 patients with neoadjuvant chemotherapy followed by surgical resection of residual diseases, 2-year survival rate was 57.1%,The 3-year survival rate was 28.6%Conclusion: An aggressive, multidisciplinary treatment including neoadjuvant chemotherapy followed by residual mass surgical resection is the optimal treatment and can be associated with prolonged survival.