Mediastinal Germ Cell Tumors Research Articles

Analysis of prognostic factors and establishment of prognostic model for primary mediastinal germ cell tumors: a case controlled study.

The overall prognosis of primary mediastinal germ cell tumors (PMGCTs) is poor and the associated prognostic factors are not fully understood. Our goal was to investigate the prognostic factors of PMGCTs and to develop a validated prognostic prediction model. A total of 114 PMGCTs with specific pathological types were included in this study. Clinicopathological characteristics of nonseminomatous PMGCTs and mediastinal seminomas were compared using the χ2 or Fisher's exact test. Independent prognostic factors of nonseminomatous PMGCTs screened using the univariate and multivariate Cox regression analysis were then used to generate a nomogram. The predictive performance of the nomogram was evaluated using the concordance index, decision curve, and the area under the receiver operating characteristic curve (AUC) and validated by bootstrap resampling. The Kaplan-Meier curves of independent prognostic factors were analyzed. This study included 71 cases of nonseminomatous PMGCTs and 43 cases of mediastinal seminomas. The 3-year overall survival rates for nonseminomatous PMGCTs and mediastinal seminomas patients were 54.5 and 97.4%, respectively. The overall survival prognostic nomogram for nonseminomatous PMGCTs was established by integrating independent prognostic factors, including the Moran-Suster stage, white blood cell, hemoglobin, and platelet-lymphocyte ratio. The nomogram demonstrated good performance with a concordance index of 0.760 and the 1-year and 3-year AUC values of 0.821 and 0.833, respectively. These values were better than those of the Moran-Suster stage system. The bootstrap validation had an AUC of 0.820 (0.724-0.915) and showed a well-fitting calibration curve. Besides, patients with mediastinal seminomas showed favorable clinical outcomes and all the nine patients received neoadjuvant therapy and postoperative surgery achieved pathological complete response. A nomogram based on staging and blood routine examination results was established to accurately and consistently predict the prognosis of patients with nonseminomatous PMGCTs.

Gene mutation landscape of a rare patient with acute megakaryoblastic leukemia after treatment of intracranial germ cell tumor.

It was first reported that germ cell tumor patients suffer from hematologic malignancies 37 years ago. Since then, the number of relevant reports has increased each year, with most cases being mediastinal germ cell tumor. Theories have been proposed to explain this phenomenon, including a shared origin of progenitor cells, the effects of treatment, and independent development. However, up to now, no widely accepted explanation exists. The case with acute megakaryoblastic leukemia and intracranial germ cell tumor has never been reported before and the association is far less known. We used whole exome sequencing and gene mutation analysis to study the relationship between intracranial germ cell tumor and acute megakaryoblastic leukemia of our patient. We report a patient who developed acute megakaryoblastic leukemia after treatment for an intracranial germ cell tumor. Through whole exome sequencing and gene mutation analysis, we identified that both tumors shared the same mutation genes and mutation sites, suggesting they originated from the same progenitor cells and differentiated in the later stage. Our findings provide the first evidence supporting the theory that acute megakaryoblastic leukemia and intracranial germ cell tumor has the same progenitor cells.

Clinical Features and Survival Outcomes in Children and Adolescents With Malignant Mediastinal Germ Cell Tumors Based on Surveillance, Epidemiology, and End Results Database Analysis

IntroductionThe 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). MethodsData 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. ResultsThe 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. ConclusionsOur 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.

Primary Mediastinal Germ Cell Tumors (PMGCT): A Real-world Analysis From A Tertiary Cancer Care Center in India

Background Primary mediastinal GCT (PMGCT) is a rare entity and comprises 10–15% of all mediastinal tumors. We present our institutional experience of MGCT treated with multimodality management. Materials and Methods We conducted a retrospective analysis between 2010 to 2020 of all mediastinal germ cell tumors registered at our center. Data on patient demographics, treatments received, treatment toxicities and response were recorded. Overall survival and relapse free survival were estimated using Kaplan–Meier methods. Results A total of 30 patients were identified. The median age was 25.5 (range, 18–45) years. Common presenting features included cough (70%) and shortness of breath (70%). Histology wise, 60% patients were non seminomatous histology, whereas 33.3% patients were Seminoma. Twenty-seven (90%) patients received chemotherapy as the first-line treatment, of whom five patients (16.6%) underwent surgery and radiation therapy subsequently. Median follow-up was 26.9 months. Thirteen patients (43.3%) had complete response (43.3%) and eight patients had partial response (26.7%), while three patients (5.5%) had progressive disease. Three-year relapse-free survival rate was 69.6% (95% confidence interval [CI], 42.8–85.6%). Overall survival (OS) at 3 years was 73.4% (95% CI, 49.4–87.3%). Patients with seminoma had a 3 year OS of 90.0% (95% CI, 47.3–98.5%) compared to those with non-seminoma (63.53% [95% CI, 32.3–83.3%]). Conclusions Multiagent chemotherapy is the backbone of treatment in PMGCT. Seminomatous PMGCT have excellent prognosis, while further improvement is needed in those with nonseminomatous tumor.

Pediatric Extracranial Germ Cell Tumors: Review of Clinics and Perspectives in Application of Autologous Stem Cell Transplantation

Pediatric extracranial germ cell tumors (GCTs) are rare, accounting for approximately 3.5% of childhood cancers. Since the introduction of platinum-based chemotherapy, the survival rate of patients has improved to more than 80%. However, poor-risk subtypes of pediatric extracranial GCTs do not respond well to chemotherapy, leading to refractory or relapsed (R/R) diseases. For example, long-term survival rates of mediastinal GCTs or choriocarcinoma are less than 50%. According to reports in recent years for adult patients with R/R GCTs, the use of high-dose chemotherapy (HDCT) combined with autologous stem cell transplantation (ASCT) has clinical advantages; however, HDCT combined with ASCT has rarely been reported in pediatric GCTs. The R/R and poor-risk groups of pediatric GCTs could benefit from HDCT and ASCT.

A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor

Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness.

Development of A Nomogram for Predicting Survival of Patients with Primary Mediastinal Germ Cell Tumor Based on SEER Database

Primary mediastinal germ cell tumor (PMGCT) is a rare but occasionally highly invasive mediastinal tumor. At present, there are few related disease special survival (DSS) studies on PMGCT, rare large data analysis, and uncommon DSS prognostic models. This study was to investigate the prognostic factors of DSS of the PMGCT patients, and build a simple and effective nomogram to predict the DSS prognosis in patients with PMGCT. Retrospective clinicopathological data of 325 patients with PMGCT from 1975 to 2019 were extracted from Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method along with the Log-rank test were utilized to estimate the DSS. Cox proportional hazard regression model was used to screen the independent risk factors affecting prognosis, from which an individualized nomogram was constructed to predict 3-yr, 5-yr and 8-yr DSS of patients with PMGCT. The prediction accuracy of the model is evaluated by receiver operating characteristic (ROC) curve, correction curve and decision curve analysis (DCA) curve. The 3-yr, 5-yr and 8-yr survival rates of PMGCT were 84.6%, 83.6% and 83.3%, respectively. Univariate analysis showed that histology, surgery, age, tumor size, metastasis and stage could affect the prognosis of PMGCT. Multivariate analysis showed that histology, surgery, age and tumor size were independent risk factors for the prognosis of PMGCT patients, and the nomogram was constructed using these independent risk factors. The area under the curve (AUC) of ROC curve was 0.824. The results of the correction curves of 3-yr, 5-yr and 8-yr survival time and DCA, indicated that there was a good consistency between the predicted results of the nomogram evaluation and the real results. Patients with histological classification of seminoma in PMGCT have a better prognosis than patients with non-seminoma. The prognosis of patients with over the age of 40 yr, tumor size ≥15 cm and without surgical treatment was even worse. The nomogram model can accurately and intuitively predict the DSS of patients with PMGCT.

Case Report: Cardiac Metastases in a Non-Seminomatous Tumor

Germ cell tumors are the most prevalent malignancy in young males commonly formed in the testicles. Primary mediastinal non-seminomatous germ cell tumors are rare, they tend to be aggressive and have unsatisfactory outcomes. Non-seminomatous cell tumors, it is the most likely testicular cancer to cause metastasis. Symptoms such as giddiness, fainting, fatigue, shortness of breath and chest discomfort are potential presentations in the emergency department on cardiac metastases. Primary mediastinal non-seminomatous germ cell tumor are considered high risk. Treatment is based on the underlying pathology, usually chemotherapy followed by surgery. Rare cases like this need to be reported and further studied to give patients better expectancy when diagnosed. The bad surveillance rate of 40 to 45% survival at 5 years and less than 10% overall is mostly due to the lack of response to aggressive chemotherapy and the concomitant pathologies that this presentation.

Primary Mediastinal Germ Cell Tumors: A Thorough Literature Review

Primary mediastinal germ cell tumors (PMGCTs) are a rare type of cancer affecting young adults. They have different molecular and clinical features compared to testicular germ cell tumors. Non-seminoma PMGCTs have the shortest 5-year overall survival and the poorest prognosis among all of the germ cell tumor presentations, while seminomas share the same survival and prognosis as their testicular counterparts. There is an unmet need for better treatment options for patients with non-seminoma PMGCTs in both first-line and salvage therapy, as the available options are associated with underwhelming outcomes. Identifying biological and genetic factors to predict treatment responses would be helpful in improving the survival of these patients.

The diagnostic value of cytogenetics in a patient with concurrent mediastinal non-seminomatous germ cell tumour (NSGCT), fibrolamellar hepatocellular carcinoma and acute megakaryoblastic leukaemia (AMKL) associated with widespread bone marrow necrosis

Background: The rare association between NSGCT and AMKL has been reported since 1985.1,2 Isochromosome 12p is the most common cytogenetic abnormality in NSGCT but is only rarely found in AMKL unless in association with NSGCT.3

Primary mediastinal germ cell tumors.

Mediastinal germ cell tumors share similar histopathological, immunohistochemical, and molecular features with their counterparts in the gonads. Therefore, proper clinical and radiological evaluation of patients with an anterior mediastinal mass becomes essential in the final interpretation of these tumors. The gold standard for the diagnosis of these tumors remains histopathological evaluation. However, immunohistochemical stains and molecular studies also provide an aid in cases in which the histology is not typical. It is also important to keep in mind that a small mediastinoscopic biopsy may not be representative of the entire neoplasm. In this review, we will provide our perspective regarding histopathological diagnosis, staging, immunohistochemical and molecular profile, and briefly family of tumors address pertinent epidemiological, clinical and treatment options. However, the main emphasis is to review the process of pathological assessment in pre and post-treated tumors. Knowledge of the different growth patterns and histological associations is important, mainly when confronted with mediastinoscopic biopsies, which ultimately will determine treatment options.

Anterior mediastinal germcell tumor with brain metastasis in a child – A case report

Anterior mediastinal germcell tumor with brain metastasis in a child – A case report

Anterior mediastinal germcell tumor with brain metastasis in a child – A case report

Anterior mediastinal germcell tumor with brain metastasis in a child – A case report

Успешное хирургическое лечение герминогенной опухоли средостения на фоне химиорезистентности

Успешное хирургическое лечение герминогенной опухоли средостения на фоне химиорезистентности

A 16-year-old Adolescent With Mediastinal Seminoma: A Case Report and Literature Review

Germ cell tumors (GCTs) are a heterogeneous group of neoplasms that arise from the primordial germ cells of the human embryo, which are normally destined to produce reproductive cells sperm, or ova. GCTs can be present in both gonadal GCTs and extragonadal GCT sites. Pediatric GCTs are relatively rare tumors with an incidence of 2%-3%. Primary mediastinal germ cell tumors GCTs are very rare extragonadal GCTs that arise in the anterior mediastinum. In this report, we present the case of a 16-year-old boy with primary seminoma arising in the anterior mediastinum. The patient presented with the symptoms of cough, fever, and chest tightness. CT finding was in favor of a large expansive process measuring 12.4x6.7x14.2 cm in the anterior mediastinum, accompanied by a conglomeration of hilar lymph nodes in the level of brachiocephalic veins juncture. Fine needle biopsy and core biopsy were performed transthoracically, under the control of MSCT. Based on histology and immunohistochemistry, the diagnosis of mediastinal germ cell tumor with immunophenotype of seminoma was made. The patient was treated with 4 cycles of chemotherapy by BEP protocol without significant side effects and toxicities. The patient remained disease-free for 16 months. The purpose of reporting this case is to confirm that chemotherapy with cisplatin-based regimens has markedly improved the outcome of adults and children with GCTs as well.

Genomic features of mediastinal germ cell tumors: a narrative review.

Germ cell tumors (GCTs) are uncommon malignancies generally originating from gonads. However, about 5% of GCTs arise outside the gonad (extragonadal), of which 80% develop from the mediastinum. While the prognosis of seminomas is not affected by the gonadal or extragonadal primary location, the prognosis of nonseminoma primary mediastinal GCTs (NS-PMGCTs) is poor, compared to its gonadal counterpart with an estimated 5-year overall survival of about 50%. The current treatments are sub-optimal to increase the cure rate of these rare GCTs. Therefore, molecular insights into these tumors would be valuable to develop novel therapies. The main objective of this review is to describe and dissect the genomic features associated with primary mediastinal GCTs (PMGCTs), highlighting the more frequent genomic alterations and their correlation with clinical outcomes. We conducted a narrative review of the English literature available in PubMed and Google Scholar between 1982 and 2021, including meta-analyses, systematic reviews, case series and case reports regarding the genomic and clinical features of PMGCTs. We analyzed the available data to describe the molecular characteristics of PMGCTs compared to testicular GCTs (TGCTs), highlighting the most relevant biological and prognostic factors. The high percentage of platinum resistance, the unique association with hematologic malignancies (HMs) and other malignancies, the higher prevalence of P53 mutations, and a distinct genomic landscape characterize this rare disease. Although some studies have unveiled recurrent molecular alterations in PMGCTs, few are particularly suitable for targeted therapy. Due to the rarity of PMGCTs, data sharing and the creation of an international consortium would be helpful to have a better understanding of the molecular drivers of these tumors.

RUPTURED MEDIASTINAL TERATOMA

Introduction: Mediastinal teratomas are the most common type of mediastinal germ cell tumor. Most patients with mediastinal teratomas remain clinically silent. However, these teratomas occasionally rupture into the thoracic cavity, causing severe complications; surgical intervention is always required for ruptured teratomas. Herein, we report that case of a large anterior mediastinal teratoma that ruptured into the pleural cavity and caused a lung infection, pleural effusion, and subsequent mediastinitis. Case Report: A 20-year-old man presented with rapidly progressive dyspnea and chest pain. Chest radiography revealed a large opacity in the entire right hemithorax. A thoracostomy tube was introduced into the right pleural cavity, and 200 mL of purulent uid was evacuated. Thoracic computed tomography (CT) revealed a mass in the right hemithorax compressing the adjacent structures. The patient underwent total resection of the mediastinal mass via right posterolateral thoracotomy. Intraoperatively, the chest cavity was lled with adhesions and pus. The teratoma ruptured and adhered to surrounding structures. Postoperatively, the patient recovered completely. Microscopy revealed a mature teratoma. Rupt Conclusion: ured mediastinal mature teratoma is a serious complication. Once it is diagnosed, early surgical excision should be performed to reduce rupture-related complications.

Atypical cartilage in type II germ cell tumors of the mediastinum show significantly different patterns of IDH1/2 mutations from conventional chondrosarcoma

AbstractNeoplastic cartilage is a common component of teratomas in type II germ cell tumors. Although IDH1/2 mutations have been well-described in somatic cartilaginous tumors, ranging from benign enchondromas to highly aggressive dedifferentiated chondrosarcomas, the presence of IDH1/2 mutations in cartilaginous neoplasms arising from germ cell tumors has not been previously investigated. To better understand the relationship between these tumors and their bone/soft tissue counterpart, we studied the IDH1/2 mutational status of 20 cases of primary mediastinal mixed germ cell tumors with areas of readily identifiable cartilaginous differentiation. Our study found that cartilaginous lesions arising in germ cell tumors have a different frequency and distribution of IDH1/2 mutations compared to those at somatic sites. We identified IDH1/2 mutations in only 15% (3/20) of cases, compared to a frequency in the literature among differentiated chondroid tumors of bone and soft tissue of 54%, a highly significant decreased frequency (p = 0.0011; chi-square test). Furthermore, they were exclusively IDH2 R172 mutations that occurred at a non-significant, increased frequency in the germ cell tumor group compared to conventional chondrosarcoma (15% vs. 5%, respectively, p > 0.05, chi-square test). The unexpected finding, therefore, was entirely attributable to the absence of IDH1 R132 mutation in chondroid neoplasia of germ cell origin (p < 0.00001, Fisher exact test). Our results suggest that a subset of cartilaginous lesions arising within type II germ cell tumors have a similar oncogenic mechanism to their bone/soft tissue counterpart but that the majority form using different oncogenic mechanisms compared to their somatic counterparts.

Surgical treatment confers prognostic significance in pediatric malignant mediastinal germ cell tumors.

Primary malignant mediastinal germ cell tumors (GCTs) are rare pediatric tumors that have a poorer prognosis compared to GCTs occurring elsewhere in the body. The current study aimed to assess the prognostic factors and treatment outcomes of children with primary malignant mediastinal GCT in Taiwan. The authors retrospectively reviewed children 0-18years old who were newly diagnosed with primary malignant mediastinal GCT between January 1, 2005 and December 31, 2019 and were registered in the Taiwan Pediatric Oncology Group patient registry. The impact of presenting characteristics, including sex, age, tumor stage, histology subtype, surgical treatment, and chemotherapy regimens of the patients were analyzed. This study enrolled 52 children with malignant mediastinal GCT who had a median age of 16.0 (range, 6.0-17.9) years at diagnosis. The most common histological subtypes were mixed GCTs (n=20) and yolk sac tumors (n=15). Advanced disease stage and choriocarcinoma histology subtype were associated inferior outcomes. Children who received surgical treatment exhibited better outcomes compared to those who did not (5-year overall survival, 78% vs. 7%, p<.001). After comparing patients who received first-line cisplatin- and carboplatin-based chemotherapy, no difference in treatment outcomes was observed. Multivariate analysis showed thatsurgical management was the only independent predictor for superior OS. Surgical treatment is recommended for mediastinal GCT. Cisplatin-based chemotherapy was not superior to carboplatin-based chemotherapy as first-line treatment and may be avoided due to toxicity concerns.

TP53 Alterations Are Associated With Poor Survival in Patients With Primary Mediastinal Nonseminoma Germ Cell Tumors.

Primary mediastinal nonseminoma germ cell tumors (PMNSGCT) are a subgroup of nonseminoma germ cell tumors (GCT) with poor prognosis. In this study, PMNSGCT-specific genomic landscape was analyzed and correlated with clinical outcomes. DNA was extracted and sequenced from 28 archival tumor tissue of patients with mediastinal GCT (3 seminoma and 25 nonseminoma). Overall survival (OS) and association with gene alterations were estimated using the Kaplan-Meier and univariate Cox regression methods. Three patients (11%) had a karyotype XXY, 17/28 (61%) tumor samples presented chromosome 12p amplification. Somatic mutations were detected in 19/28 (68%) samples. The most frequently mutated genes were: TP53 (13/28; 46%), KIT (5/28; 18%), and KRAS (5/28; 18%). Deleterious TP53 alterations were associated with significantly reduced overall survival (HR: 7.16; P = .012). TP53 alterations are common in PMNSGCT and are associated with reduced overall survival, potentially underlying the poor sensitivity to chemotherapy observed in these patients.