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The Journal of Surgical Research Aug 2023The purpose of this study was to perform a population-based investigation to assess the disease characteristics and prognosis of children and adolescents with malignant...
Clinical Features and Survival Outcomes in Children and Adolescents With Malignant Mediastinal Germ Cell Tumors Based on Surveillance, Epidemiology, and End Results Database Analysis.
INTRODUCTION
The purpose of this study was to perform a population-based investigation to assess the disease characteristics and prognosis of children and adolescents with malignant mediastinal germ cell tumors (MMGCT).
METHODS
Data on the demographics, treatment, and survival outcomes of children and adolescents with MMGCT from January 1, 2000 to December 31, 2018 were obtained. To compare survival curves, the log-rank test was employed. The generation of survival curves based on different parameters was done using Kaplan-Meier estimations. Cox proportional hazards regression was performed to determine the variables linked to disease-specific survival.
RESULTS
The selection criteria were met by 152 MMGCT patients, 130 of whom were male. Fifty three cases of mixed germ cell tumors (GCTs), 41 cases of malignant teratomas, 26 cases of yolk sac tumors, 14 cases of seminoma, 13 cases of choriocarcinomas, and five cases of embryonal carcinoma were reported. Overall survival at 3 and 5 y for all patients was 63.1% and 61.2%, respectively. Malignant teratoma, yolk sac tumors, and mixed GCTs in children and adolescents had comparable survival rates, while those with choriocarcinoma and embryonal carcinoma showed the worst prognosis. Embryonal carcinoma, malignant teratoma, mixed GCTs, and choriocarcinoma were found as risk factors by multivariate Cox proportional hazards analysis. In contrast, surgery and younger age were protective factors. However, chemotherapy alone showed no survival benefits.
CONCLUSIONS
Our population-based evidence showed that MMGCT had worse prognosis in older children and adolescents. Choriocarcinomas and embryonal carcinomas had the worst prognosis. Surgery can prolong survival time. Chemotherapy and radiotherapy were not associated with improved prognosis.
Topics: Pregnancy; Female; Humans; Male; Child; Adolescent; Carcinoma, Embryonal; Endodermal Sinus Tumor; Neoplasms, Germ Cell and Embryonal; Teratoma; Mediastinal Neoplasms; Choriocarcinoma; Testicular Neoplasms
PubMed: 37062232
DOI: 10.1016/j.jss.2023.03.018 -
Histopathology Sep 2023Yolk sac tumour postpubertal-type (YSTpt) shows a wide range of histological patterns and is challenging to diagnose. Recently, forkhead box transcription factor A2...
AIMS
Yolk sac tumour postpubertal-type (YSTpt) shows a wide range of histological patterns and is challenging to diagnose. Recently, forkhead box transcription factor A2 (FoxA2) emerged as a driver of YSTpt formation and a promising marker for diagnosing YSTpt. However, FoxA2 has not been tested in the different patterns of YSTpt. This study aimed to assess the staining pattern of FoxA2 in te different patterns of YSTpt and other germ cell tumours of the testis (GCTT), comparing it with glypican-3 (GPC3) and α-fetoprotein (AFP).
METHODS AND RESULTS
FOXA2, GPC3 and AFP immunohistochemistry was performed on 24 YSTpt (24 microcystic/reticular, 10 myxoid, two macrocystic, five glandular/alveolar, two endodermal sinus/perivascular, four solid, two polyembryoma/embryoid body and two polyvesicular vitelline) and 81 other GCTT. The percentage of positive cells (0, 1+, 2+, 3+) and the intensity (0, 1, 2, 3) were evaluated regardless of and within each YSTpt pattern. FoxA2 was positive in all YSTpt (24 of 24) and all but one (23 of 24) exhibited 2+/3+ stain, with higher intensity [median value (mv): 2.6] than AFP (1.8) and GPC3 (2.5). Both FoxA2 and GPC3 were positive in all microcystic/reticular (24 of 24), myxoid (10 of 10), macrocystic (two of two), endodermal sinus/perivascular (four of four) and polyembryoma/embryoid body (two of two) patterns. Nevertheless, only FoxA2 was positive in all glandular/alveolar (five of five), solid (four of four) and polyvesicular vitelline (two of two) patterns. The intensity of FoxA2 was higher than AFP and GPC3 in almost all YST patterns. In the other GCTT, FoxA2 was positive only in teratoma postpubertal-type (Tpt) [13 of 20 (65%)], with staining almost exclusively confined to the mature gastrointestinal/respiratory tract epithelium.
CONCLUSIONS
FoxA2 is a highly sensitive and specific biomarker that supports the diagnosis of YSTpt. FoxA2 is superior to GPC3 and AFP, especially in rare and difficult-to-diagnose histological patterns of YSTpt, but mature glands of Tpt could represent a potential diagnostic pitfall.
Topics: Male; Humans; Female; alpha-Fetoproteins; Biomarkers, Tumor; Endodermal Sinus Tumor; Testicular Neoplasms; Cysts; Ovarian Neoplasms; Glypicans
PubMed: 37317674
DOI: 10.1111/his.14968 -
Human Immunology Oct 2023Immune checkpoint blockade (ICB) is considered as a promising approach for cancer treatment. However, the potency of ICB therapy in yolk sac tumors (YSTs) has not been...
BACKGROUND
Immune checkpoint blockade (ICB) is considered as a promising approach for cancer treatment. However, the potency of ICB therapy in yolk sac tumors (YSTs) has not been confirmed, and the comprehensive analysis of tumor immune microenvironment and the expression of PD-1/PD-L1 and CTLA4 were also not thoroughly evaluated.
METHODS
Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tumor specimens from 23 YSTs patients to detect the density and distribution of tumor-infiltrating T cells, tertiary lymphoid structures (TLSs), as well as the expression of PD-1/PD-L1 and CTLA4.
RESULTS
Overall, more than half (61 %) of all patients exhibited an immune-desert phenotype based on CD3 T cells. PD-1 expression was identified in five tumor samples (21.7 %), and PD-L1 expression exhibited a different positive rate in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) (39.1 % and 17.4 %). Noteworthily, the rate of positive CTLA4 expression in both TCs and TILs was markedly higher (69.6 % and 56.5 %) than those of PD-1 and PD-L1 expression. Furthermore, TLSs were observed in 21.74 % of all tissues, and samples with TLSs exhibited significantly higher densities of TILs and higher expression of immune checkpoint molecules, particularly PD-1/PD-L1. In addition, tumors located in testes also exhibited a higher density of TILs and higher expression of immune checkpoint molecules.
CONCLUSION
Generally a high frequency of CTLA4 expression was found, PD-1/PD-L1 expression, the immune-inflamed phenotype, and TLSs were low frequency in YSTs, however, YSTs in testes showed a higher density of TILs and higher expression of immune checkpoint molecules.
Topics: Humans; B7-H1 Antigen; CTLA-4 Antigen; Endodermal Sinus Tumor; Immune Checkpoint Proteins; Lymphocytes, Tumor-Infiltrating; Prognosis; Programmed Cell Death 1 Receptor; Tumor Microenvironment
PubMed: 37453913
DOI: 10.1016/j.humimm.2023.07.003 -
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 -
Zhonghua Fu Chan Ke Za Zhi Mar 2024To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). The clinicopathological data and follow-up data of 12 patients with OYST...
To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA) detection results, 9 patients showed elevated serum CA levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.
Topics: Pregnancy; Child; Humans; Female; Young Adult; Adult; Adolescent; alpha-Fetoproteins; Endodermal Sinus Tumor; Retrospective Studies; Neoplasm Staging; Antineoplastic Combined Chemotherapy Protocols; Ovarian Neoplasms; Neoplasms, Germ Cell and Embryonal
PubMed: 38544450
DOI: 10.3760/cma.j.cn112141-20231121-00212 -
BMC Women's Health Jun 2023Yolk sac tumour (YST) is the second most common ovarian germ cell tumour and usually presents in children and young women. However, tumours rarely occur as malignant...
BACKGROUND
Yolk sac tumour (YST) is the second most common ovarian germ cell tumour and usually presents in children and young women. However, tumours rarely occur as malignant gynaecological tumours with YST components.
CASE PRESENTATION
We present one case of endometrioid carcinoma and clear cell carcinoma with YST components and two other cases of YSTs associated with high-grade serous carcinoma of the ovary in females. After surgery and adjuvant chemotherapy, the patient with endometrioid carcinoma had progressive disease and died 20 months later, and the other two were still alive at the last follow-up.
CONCLUSIONS
To our knowledge, these mixed neoplasm associations are unusual, and these cases illustrate the diagnosis and prognosis of YST associated with malignant gynaecological tumours, emphasizing early recognition and aggressive treatment.
Topics: Female; Humans; Adenocarcinoma, Clear Cell; Carcinoma, Endometrioid; Endodermal Sinus Tumor; Genital Neoplasms, Female; Ovarian Neoplasms
PubMed: 37391759
DOI: 10.1186/s12905-023-02495-w -
The Journal of Pathology Jun 2024Mesonephric adenocarcinomas (MAs) and mesonephric-like adenocarcinomas (MLAs) are rare, aggressive neoplasms that arise in the gynecologic tract and show overlapping...
Mesonephric adenocarcinomas (MAs) and mesonephric-like adenocarcinomas (MLAs) are rare, aggressive neoplasms that arise in the gynecologic tract and show overlapping morphologic, immunohistochemical, and molecular features. While MAs occur in the cervix and are thought to arise from mesonephric remnants, MLAs occur in the endometrium and ovary and are believed to originate from transdifferentiation of Müllerian lesions. Both MAs and MLAs show a variety of architectural patterns, exhibit frequent expression of GATA3 by immunohistochemistry, and harbor KRAS mutations. In a recent article published in The Journal of Pathology, Kommoss and colleagues used DNA methylation profiling to extend these similarities and showed that MLAs and MAs cluster together based on their epigenetic signatures and are epigenetically distinct from other Müllerian adenocarcinomas. They also showed that MLAs and MAs harbor a high number of global copy number alterations. This study provides evidence that MLAs more closely resemble MAs than Müllerian carcinomas on an epigenetic level. As a result, the authors argue that MLA should be renamed 'mesonephric-type adenocarcinoma.' Further research is needed to establish the relationship between these two entities, their etiology, and pathogenesis. © 2024 The Pathological Society of Great Britain and Ireland.
Topics: Humans; Adenocarcinoma; Female; Epigenesis, Genetic; Uterine Cervical Neoplasms; DNA Methylation; Mullerian Ducts; Mesonephroma; Biomarkers, Tumor; Epigenome
PubMed: 38593211
DOI: 10.1002/path.6285 -
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 -
International Urology and Nephrology Nov 2023The aim of this study was to identify epidemiological and histopathological patterns of pediatric testicular tumor (TT) in Saudi population over 10 years.
BACKGROUND/OBJECTIVE
The aim of this study was to identify epidemiological and histopathological patterns of pediatric testicular tumor (TT) in Saudi population over 10 years.
METHODS
Retrospective data extracted from the Saudi Cancer Registry for Saudi children diagnosed with TT from 2008 to 2017. The data collected included patient's factors as age, year of diagnosis, survival status, and tumor factors as basis of diagnosis, origin of the tumor, histopathological group and subtype, and tumor behavior, stage, and laterality.
RESULTS
A total of 115 patients with a median age of 14 (IQR 1.5-17) were included. The primary tumor site was a normal descended testis in 98.3% (115). Yolk sac tumor was the most common 28.2% (33), followed by embryonal carcinoma in 27.4% (32) and mixed germ-cell tumors in 23.1% (27). Kaplan-Meier analysis revealed significant association between survival and the stage of the tumor (p = 0.002). However, there was a lack of significant association between survival and age groups, histopathological groups, and histopathological subtypes (p = 0.541, p = 0.609, and p = 0.733, respectively). The overall mortality rate of TT 5.2% with all deaths caused by non-seminomatous germ-cell tumor diagnosed with stage 3.
CONCLUSIONS
The median age of the patients was 14 years. Yolk sac tumors were the most common while testicular choriocarcinomas were the least in incidence. No increase in the incidence of TT was seen and the mortality rate over the 10-year period was 5.2%. Shorter survival was associated with higher tumor stage.
Topics: Male; Humans; Child; Adolescent; Retrospective Studies; Saudi Arabia; Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Endodermal Sinus Tumor
PubMed: 37477777
DOI: 10.1007/s11255-023-03701-2 -
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