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

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xuan Zong ◽  
Ying Zhang ◽  
Xinxin Peng ◽  
Dongyan Cao ◽  
Mei Yu ◽  
...  
Keyword(s):  
Copy Number Alteration ◽  
Germ Cell Tumors ◽  
Gonadal Development ◽  
Yolk Sac ◽  
Mutational Signatures ◽  
Whole Exome ◽  
Genomic Landscape ◽  
Yolk Sac Tumors ◽  
Molecular Aberrations

AbstractYolk 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.

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

2021 ◽  
Author(s):  
Clinton Hall ◽  
Johnni Hansen ◽  
Jørn Olsen ◽  
Di He ◽  
Ondine S. von Ehrenstein ◽  
...  
Keyword(s):  
Germ Cell ◽  
Maternal Employment ◽  
Case Control Study ◽  
Germ Cell Tumors ◽  
Social Contact ◽  
Case Control ◽  
Yolk Sac ◽  
Parental Occupation ◽  
Yolk Sac Tumors ◽  
Control Study

Abstract 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.

scholarly journals Ovarian Yolk Sac Tumor: A Case Report with Review Of Literature

2016 ◽  
Vol 2 (1) ◽  
pp. 15-17
Author(s):  
A Sreehari ◽  
BM Rupakala
Keyword(s):  
Case Report ◽  
Early Adulthood ◽  
Germ Cell Tumors ◽  
Yolk Sac ◽  
Immature Teratoma ◽  
Yolk Sac Tumor ◽  
Histological Subtype ◽  
Review Of Literature ◽  
Yolk Sac Tumors ◽  
Ovarian Dysgerminoma

ABSTRACT A total of 3 to 5% of all ovarian malignancies include malignant ovarian germ cell tumors (MOGCTs). They are subdivided into germinomatous and non-germinomatous tumors. Common types of non-germinomatous tumors include yolk sac and immature teratoma. Ovarian yolk sac tumors (YST) are the second most frequent histological subtype of MOGCTs, after ovarian dysgerminoma. They account for 20% of MOGCTs and are frequent especially in childhood and in early adulthood. We report the case of a yolk sac tumor of the ovary in a 13yrs years old female. How to cite this article Sreehari A, Rupakala BM, Sarojamma C. Ovarian Yolk Sac Tumor: A Case Report with Review of Literature. J Med Sci 2016;2(1):15-17.

Site of metastases does not influence the clinical outcome of children with metastatic Germ Cell Tumors (GCT). A report from the Childrens Oncology Group (COG)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9002-9002
Author(s):  
M. H. Malogolowkin ◽  
W. B. London ◽  
B. Cushing ◽  
R. Giller ◽  
M. Davis ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Stage Iv ◽  
Yolk Sac ◽  
Cell Tumor ◽  
High Dose ◽  
Metastatic Site ◽  
Yolk Sac Tumors

9002 Background: To describe the clinical outcome of children with metastatic GCT (stage IV) at diagnosis according to the primary metastatic site(s). Methods: From March 1990 to February 1996, 299 children and adolescents with stage III/IV gonadal and stage I-IV extragonadal GCT were eligible for a Pediatric Intergroup high-risk (HR) GCT trial. Patients were randomized to receive 4–6 courses of cisplatin (P) standard dose [ 20 mg/m2/day (d) × 5] or high-dose (HDP) [40 mg/m2/d × 5] with etoposide (E) 100 mg/m2/d × 5 and bleomycin (B) 15 mg/m2 on d1. We retrospectively investigated the outcome of patients with stage IV and compared their outcome according to metastatic site(s). Results: There were 133 patients with stage IV disease. The median age was 2.6 years (y) [range, 3 d-19.3 y], 70 were female. Primary sites included: 43 testicular, 14 ovarian, 76 extragonadal (45 sacroccocygeal, 28 mediastinal, 3 other). Histologies included: 66 pure yolk sac tumors, 21 immature teratomas and yolk sac tumors, 26 mixed germ cell tumors, 7 pure germinoma/seminoma/dysgerminomas, 1 immature teratoma with a non-classic germ cell tumor, 2 mixed germ cell tumor admixed with a nonclassic germ cell tumor, 5 pure choriocarcinomas, and 5 patients with unknown histology. There were no statistically significant differences in the 5-year EFS or OS rates by site of metastases. Of the 19 patients with either bone or brain involvement, 17 patients had bone and 3 had brain metastases. Conclusion: The outcome for patients with metastatic GCT is excellent with contemporary cisplatin-based regimes and is independent of the site of metastatic disease. [Table: see text] No significant financial relationships to disclose.

Primary Yolk Sac Tumor of the Urachus

2002 ◽  
Vol 126 (9) ◽  
pp. 1106-1109 ◽  
Author(s):  
Hsuan-Ying Huang ◽  
Sheung-Fat Ko ◽  
Jiin-Haur Chuang ◽  
Yung-Ming Jeng ◽  
Ming-Tse Sung ◽  
...  
Keyword(s):  
Tumor Cells ◽  
P53 Protein ◽  
Germ Cell Tumors ◽  
Male Infant ◽  
Yolk Sac ◽  
Yolk Sac Tumor ◽  
Resected Specimen ◽  
Abdominal Tumor ◽  
Yolk Sac Tumors ◽  
Urachal Adenocarcinoma

Abstract Pure yolk sac tumor is the most common malignant gonadal tumor of infants and toddlers. However, the majority of extragonadal germ cell tumors in the midline are either seminomas (germinomas) or teratomas, and pure yolk sac tumors account for only a small fraction of these lesions. To date, only 1 primary urachal pure yolk sac tumor has been reported in the literature. We describe another case, occurring in a 7-month-old male infant who presented with a rapidly enlarging intra-abdominal tumor with marked engorgement of the superficial venous plexus around the umbilicus. With periodic follow-up for 3 years following surgical extirpation of the tumor and adjuvant chemotherapy, this patient is still alive without evidence of disease. Notably, the glandular elements predominating in the frozen sections resulted in the initial misdiagnosis of the tumor as a urachal adenocarcinoma, although the entirely resected specimen revealed typical histologic patterns and Schiller-Duval bodies. Immunohistochemistry showed that the tumor cells were diffusely reactive to α-fetoprotein, α1-antitrypsin, and cytokeratin. Tumor cells were negative for p53 protein, but revealed overexpression for MDM2 protein. Flow cytometry demonstrated a diploid DNA content with S-phase being as high as 55.36%. This case emphasizes that pure yolk sac tumor can occur primarily in the remnant of the urachus in young children.

Vaginal Yolk Sac Tumors: Our Experiences and Results

2017 ◽  
Vol 27 (7) ◽  
pp. 1489-1493 ◽  
Author(s):  
Zhen Yuan ◽  
Dongyan Cao ◽  
Jiaxin Yang ◽  
Shen Keng ◽  
Huifang Huang
Keyword(s):  
Histopathological Examination ◽  
Germ Cell Tumors ◽  
Normal Serum ◽  
Yolk Sac ◽  
Yolk Sac Tumors ◽  
Long Term Follow Up ◽  
Low Incidence ◽  
Abnormal Vaginal Bleeding ◽  
Malignant Germ Cell Tumors

ObjectiveVaginal yolk sac tumors (YSTs) are rare malignant germ cell tumors largely affecting children younger than 3 years. Because of their low incidence, there is no consensus regarding diagnosis and treatment. In this article, we describe the presentation, diagnosis, treatment, and outcomes of 16 patients with vaginal YSTs diagnosed and managed at our center.MethodsDiagnoses of YST of the vagina were confirmed by 2 experienced pathologists. All patients were treated with bleomycin, etoposide, and cisplatin (PEB) combination chemotherapy alone. Complete remission (CR) was defined by a normal serum α-fetoprotein (AFP) level, no tumor detected on computed tomography, and negative pathology results. Biochemical CR (bCR) was defined by a normal serum AFP level. Long-term follow-up was completed according to our regulations.ResultsThe median age of patients at diagnosis was 10 months (range, 5–44 months), and all patients presented with abnormal vaginal bleeding and/or vaginal discharge. Serum αAFP is a sensitive tumor marker, and it was markedly elevated in all patients (median 4848 ng/mL; baseline at our hospital is <20 ng/mL). Thirteen patients completed a chemotherapy regimen consisting of PEB alone without surgery. Importantly, all patients achieved CR. Patients received additional cycles of consolidation chemotherapy after bCR and there are no cases of recurrence to date.ConclusionsWe propose a contemporary treatment strategy in line with current practice. First, all suspected cases of vaginal YST should be diagnosed by histopathological examination and serum AFP levels. Second, nonsurgical treatment with PEB chemotherapy should be initiated until patients achieve bCR, followed by an additional 2 cycles of consolidation therapy to optimize results and reduce the risk of remission.

Yolk Sac Tumors of the Head and Neck in Aicardi Syndrome

2019 ◽  
Vol 129 (3) ◽  
pp. 301-305
Author(s):  
Madison V. Epperson ◽  
Hayley L. Born ◽  
Dehua Wang ◽  
Charles M. Myer
Keyword(s):  
Head And Neck ◽  
Poor Prognosis ◽  
Germ Cell Tumors ◽  
Yolk Sac ◽  
Diagnosis And Treatment ◽  
Tissue Diagnosis ◽  
Chemotherapeutic Response ◽  
Yolk Sac Tumors ◽  
Aicardi Syndrome ◽  
Radiologic Evidence

Objectives: To understand that yolk sac tumors (YSTs) of the head and neck (H&N) are exceedingly rare and typically carry a poor prognosis. To acknowledge the possibility of increased incidence in patients with Aicardi Syndrome and the ramifications this has on early diagnosis and treatment in this population. Methods: To date, four germ cells tumors of the H&N have been reported in patients with Aicardi Syndrome. This report presents the second known case of a H&N YST in a patient with Aicardi syndrome. In both cases, the patient was initially misdiagnosed given unconvincing radiologic evidence. However, tissue diagnosis and elevated alpha-fetoprotein (AFP) levels were suggestive of a YST. Results: In contrast to the poor prognosis previously described, both patients with Aicardi syndrome had an excellent chemotherapeutic response exhibited by normalization of AFP levels and imaging. Conclusions: Rare germ cell tumors of the H&N, such as YSTs, have now been documented in several patients with Aicardi syndrome, indicating a possible association given the rarity of these tumors in the population. YSTs should be considered in the differential diagnosis of H&N masses in these patients, with emphasis on early tissue diagnosis and treatment.

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

2021 ◽  
pp. ijgc-2021-002575
Author(s):  
Giorgia Mangili ◽  
Giorgio Giorda ◽  
Gabriella Ferrandina ◽  
Gennaro Cormio ◽  
Chiara Cassani ◽  
...  
Keyword(s):  
Germ Cell ◽  
Prospective Observational Study ◽  
Germ Cell Tumors ◽  
Yolk Sac ◽  
Stage I ◽  
Routine Surveillance ◽  
Yolk Sac Tumors ◽  
Group A ◽  
Stage Ia ◽  
Group B

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.

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