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European Journal of Surgical Oncology :... Mar 2024Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST.
METHODS
Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586).
RESULTS
Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS.
CONCLUSION
Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.
Topics: Male; Adult; Humans; Child; Young Adult; Female; Endodermal Sinus Tumor; Mediastinal Neoplasms; Mediastinum; Neoplasms, Germ Cell and Embryonal; Neoadjuvant Therapy
PubMed: 38359725
DOI: 10.1016/j.ejso.2024.108019 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Feb 2024
Topics: Female; Humans; Endodermal Sinus Tumor; Adenocarcinoma; Uterus; Biomarkers, Tumor
PubMed: 38281794
DOI: 10.3760/cma.j.cn112151-20231016-00272 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jan 2024
Topics: Female; Humans; Endodermal Sinus Tumor; Adenocarcinoma; Choriocarcinoma
PubMed: 38178758
DOI: 10.3760/cma.j.cn112151-20230919-00192 -
Virchows Archiv : An International... Apr 2024In the post-chemotherapy setting, germ cell tumors of the testis (GCTT) that resemble non-specific sarcomas and co-express cytokeratins and glypican-3 (GPC3) are...
Analysis of GATA3 and FOXA2 expression suggests that downregulation of genes involved in the maintenance of a mature yolk sac tumor phenotype may underlie sarcomatoid transformation.
In the post-chemotherapy setting, germ cell tumors of the testis (GCTT) that resemble non-specific sarcomas and co-express cytokeratins and glypican-3 (GPC3) are diagnosed as "sarcomatoid yolk sac tumor postpubertal-type (YSTpt)". The diagnosis of sarcomatoid YSTpt is clinically relevant but challenging due to its rarity, non-specific histology, and negative α-fetoprotein (AFP) staining. Recently, FOXA2 has emerged as a key-gene in the reprogramming of GCTT (activating the transcription of several genes, among which GATA3), and immunohistochemical studies showed that GATA3 and FOXA2 have a higher sensitivity for non-sarcomatoid YSTpt than GPC3 and AFP. We found that sarcomatoid YSTpt did not express FOXA2 [0: 14/14 (100%)] and showed focal expression of GATA3 [0: 12/14 (85.7%), 1 + : 2/14 (14.3%)], thus suggesting that these markers are not useful in diagnosing this tumor. Furthermore, we proposed a potential mechanism of sarcomatoid transformation in the post-chemotherapy setting of GCTT, mediated by the downregulation of FOXA2 and GATA3.
Topics: GATA3 Transcription Factor; Humans; Hepatocyte Nuclear Factor 3-beta; Male; Testicular Neoplasms; Biomarkers, Tumor; Down-Regulation; Endodermal Sinus Tumor; Phenotype; Cell Transformation, Neoplastic; Immunohistochemistry; Glypicans; Adult; Sarcoma; Gene Expression Regulation, Neoplastic; Neoplasms, Germ Cell and Embryonal; Young Adult; Adolescent
PubMed: 38141134
DOI: 10.1007/s00428-023-03725-0 -
Medicine Dec 2023Primary hepatic yolk sac tumors (YSTs) are rare in adults. Liver resection is an acknowledged treatment modality for primary hepatic YST. Liver transplantation may offer... (Review)
Review
RATIONALE
Primary hepatic yolk sac tumors (YSTs) are rare in adults. Liver resection is an acknowledged treatment modality for primary hepatic YST. Liver transplantation may offer a possible cure for unresectable cases.
PATIENT CONCERNS
We present a case of a 31-year-old woman with an abdominal mass who had abnormally elevated alpha-fetoprotein (AFP) levels (31,132 ng/mL; normal: 0-7 ng/mL). Contrast-enhanced computed tomography (CT) revealed large tumors located in both lobes of the liver, with arterial enhancement and venous washout. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT indicated increased 18F-FDG uptake (maximum standardized uptake value, 24.4) in the liver tumors and left middle intra-abdominal nodule.
DIAGNOSES
The diagnosis was primary hepatic YST with metastasis to the greater omentum.
INTERVENTIONS
The patient underwent orthotopic liver transplantation and intra-abdominal nodule resection after transarterial chemoembolization (TACE) as a bridge. Intraoperatively, an intra-abdominal nodule was confirmed in the greater omentum. Histopathological examination of the liver tumors revealed Schiller-Duval bodies. The tropomyosin receptor kinase (TRK) inhibitor larotrectinib was administered, followed by four cycles of chemotherapy with bleomycin, etoposide, and cisplatin based on the next-generation sequencing results.
OUTCOMES
The AFP level decreased to within the normal range. No evidence of tumor collapse was observed during the 34-month follow-up period.
LESSONS
This case suggests that multimodal therapy dominated by liver transplantation, including preoperative TACE, postoperative adjuvant chemotherapy, and TRK inhibitors, is an effective treatment modality for unresectable primary hepatic YST.
Topics: Adult; Female; Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Fluorodeoxyglucose F18; Liver Transplantation; alpha-Fetoproteins; Endodermal Sinus Tumor; Chemoembolization, Therapeutic
PubMed: 38115376
DOI: 10.1097/MD.0000000000035821 -
Cancer Medicine Dec 2023Glypican-3 (GPC3) is highly expressed in testicular yolk sac tumor (TYST). GPC3 has been evaluated as a cancer vaccine for some types of tumors, but little is known on...
Administration of a glypican-3 peptide increases the infiltration and cytotoxicity of CD8 T cells against testicular yolk sac tumor, associated with enhancing the intratumoral cGAS/STING signaling.
BACKGROUND
Glypican-3 (GPC3) is highly expressed in testicular yolk sac tumor (TYST). GPC3 has been evaluated as a cancer vaccine for some types of tumors, but little is known on the effects of GPC3 peptide-based therapy on TYST. Here, we evaluated the antitumor effect of GPC3 on TYST and its potential mechanisms.
METHODS
GPC3 -specific CD8 T cells were induced by vaccine immunization and examined by ELISPOT. The CD8 T cells were purified for testing their cytotoxicity in vitro against TYST cells by CCK-8 and TUNEL assays and in vivo against tumor growth. The influence of GPC3 loading and/or cGAS silencing on the tumor growth, apoptosis and cGAS/STING signaling was tested by immunohistochemistry, immunofluorescence, flow cytometry, and Western blot.
RESULTS
Vaccination with GPC3 induced tumor-specific CD8 T cells that secreted high levels of IFN-γ and granzyme B, and had potent cytotoxicity against TYST in a dose-dependent manner. Adoptive transfer of CD8 T cells and treatment with GPC3 significantly inhibited the growth of TYST tumors, but less effective for cGAS-silenced TYST tumors in vivo. Treatment with GPC3 enhanced the infiltration of CD8 T cells into the tumor environment and their cytotoxicity against TYST tumors in vivo by up-regulating granzyme B and IFN-β expression, but down-regulating GPC3 expression in the tumors. Co-culture of CD8 T cells with TYST in the presence of exogenous GPC3 enhanced peptide-specific CD8 T-cell cytotoxicity in vitro, accompanied by enhancing cGAS, γH2AX, TBK1, and IRF3 phosphorylation in TYST cells, but less effective in cGAS-silenced TYST cells.
CONCLUSIONS
These data indicated that GPC3 peptide-specific CD8 T cells had potent antitumor activity against TYST tumor, particularly for combined treatment with the peptide, which was partially dependent on the intratumoral cGAS/STNG signaling. GPC3 peptide vaccine may be valuable for the combination treatment of TYST.
Topics: Male; Humans; CD8-Positive T-Lymphocytes; Granzymes; Endodermal Sinus Tumor; Glypicans; Peptides; Testicular Neoplasms; Nucleotidyltransferases
PubMed: 37986544
DOI: 10.1002/cam4.6605 -
Fetal and Pediatric Pathology 2024Testicular mixed germ cell tumor is common in the post-pubertal age, less so in prepuberty. There are only 3 reports of prepubertal mixed teratoma and yolk sac tumor....
BACKGROUND
Testicular mixed germ cell tumor is common in the post-pubertal age, less so in prepuberty. There are only 3 reports of prepubertal mixed teratoma and yolk sac tumor. Two of these cases had immature teratoma component and were in the neonatal age group. The third case in a toddler had a mature teratoma component.
CASE REPORT
An 18-month-old boy presented with a testicular mass. Serum AFP was elevated (2200 ng/ml). The orchidectomy specimen contained a yolk-sac tumor and a small epidermoid cyst, indicating a mature teratomatous component.
CONCLUSION
We report a testicular mixed teratoma and yolk sac tumor, prepubertal type along with summary of prior published cases. There is only one report describing this combination of mature teratoma with yolk sac tumor in the prepubertal testis.
Topics: Male; Infant, Newborn; Humans; Infant; Endodermal Sinus Tumor; Teratoma; Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal
PubMed: 37946365
DOI: 10.1080/15513815.2023.2279132 -
BMJ Case Reports Nov 2023Paediatric germ cell tumours (GCT) are rare tumours and are unique because of varied clinical presentation and locations. Yolk sac tumour is the predominant malignant...
Paediatric germ cell tumours (GCT) are rare tumours and are unique because of varied clinical presentation and locations. Yolk sac tumour is the predominant malignant histology and a serum marker; alpha fetoprotein is used to see treatment response and recurrent disease. It is extremely rare to find a retroperitoneal GCT with tumour thrombus extending up to the cavo-atrial region with involvement of the hepatic veins. We report a case of retroperitoneal yolk sac tumour (RPYST) with extension to the liver and right adrenal gland along with tumour thrombus in the inferior vena cava and in the right and middle hepatic veins. The child was operated after satisfactory response to chemotherapy. Excision of the tumour along with the right adrenal gland and around 5 cm of retro-hepatic caval resection was done. Inferior vena cava resection was tolerated without reconstruction. Currently child is disease-free and symptom-free at 22 months of follow-up with normal serum marker.
Topics: Humans; Child; Hepatic Veins; Endodermal Sinus Tumor; Atrial Fibrillation; Thrombosis; Vena Cava, Inferior; Liver; Adrenal Glands; Neoplasms, Germ Cell and Embryonal
PubMed: 37923340
DOI: 10.1136/bcr-2023-255968 -
Gynecologic Oncology Nov 2023To evaluate the survival outcomes and establish a risk stratification system in patients with ovarian yolk sac tumors (OYST).
OBJECTIVE
To evaluate the survival outcomes and establish a risk stratification system in patients with ovarian yolk sac tumors (OYST).
METHODS
The recurrence-free survival (RFS), disease-specific survival (DSS), and prognostic factors were retrospectively evaluated in 151 OYST patients treated in our hospital between 2006 and 2022. A risk stratification system based on the identified prognostic factors was established.
RESULTS
The median follow-up time was 5.1 years, with a 5-year RFS and DSS rate of 75.5% and 91.2%, respectively. FIGO stage III-IV and the interval between treatment and normalization of AFP were two prognostic predictors. Significant differences in RFS and DSS (both P < 0.001) were identified between patients who had normalized AFP ≤ 3 and ≥ 4 cycles of chemotherapy, or among patients who had normalized AFP after ≤2, 3-4, and ≥ 5 cycles of chemotherapy. FIGO stage I - II and stage III-IV were scored as 0 and 2, respectively. AFP normalization ≤2, 3, 4, and ≥ 5 cycles of chemotherapy were scored as 0, 1, 2, and 4, respectively. A total score of 0-1, 2-3, and ≥ 4 were stratified patients into low-risk (96 patients), intermediate-risk (35 patients), and high-risk groups (20 patients), respectively. Patients in three risk stratifications manifested significant differences in both RFS and DSS (P < 0.0001).
CONCLUSION
This risk stratification system based on tumor stage and the interval between treatment and normalization of AFP may help to guide clinical management by dividing OYST patients into three risk groups.
Topics: Female; Humans; Neoplasm Staging; alpha-Fetoproteins; Endodermal Sinus Tumor; Retrospective Studies; Prognosis; Ovarian Neoplasms; Risk Assessment
PubMed: 37865050
DOI: 10.1016/j.ygyno.2023.10.006 -
World Journal of Urology Nov 2023Yolk sac tumors (YST) are a rare and aggressive germ cell tumor. We aimed to conduct a population-based cohort study and develop a nomogram to predict overall survival...
PURPOSE
Yolk sac tumors (YST) are a rare and aggressive germ cell tumor. We aimed to conduct a population-based cohort study and develop a nomogram to predict overall survival (OS) in pediatric patients with YST.
METHODS
The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all pediatric patients with YST diagnosed between 2000 and 2018. The log-rank test was used to compare survival curves. To examine the impact of each factor on overall survival, a multivariate Cox proportional hazards model was created. Based on the results of the Cox regression model, a nomogram was constructed.
RESULTS
A total of 520 YST patients were identified. Overall survival rates for all patients were 92.2% at 3-year and 90.3% at 5-year, respectively. The outcome of Cox proportional hazard regression revealed that age, gender, primary sites, and treatment regimens were important independent predictors in this model. Based on the Cox regression model, we created a nomogram for predicting OS in pediatric YST patients. The chance of death increased with age in patients. Furthermore, patients with extra-gonadal YST have a lower survival rate than those with gonadal YST.
CONCLUSIONS
Our study revealed that age, gender, and primary site were found to be the most important predictors of the overall survival of pediatric YST, providing crucial epidemiological information for clinical management.
Topics: Child; Humans; Adolescent; Prognosis; Endodermal Sinus Tumor; Cohort Studies; Neoplasms, Germ Cell and Embryonal; Nomograms
PubMed: 37747514
DOI: 10.1007/s00345-023-04616-4