Malignant Mediastinal Germ Cell Tumors Research Articles

18F]fluorodeoxyglucose positron emission tomography/computed tomography characteristics of primary mediastinal germ cell tumors

Primary mediastinal germ cell tumor (MGCT) is an uncommon tumor. Although it has histology similar to that of gonadal germ cell tumor (GCT), the prognosis for MGCT is generally worse than that for gonadal GCT. We performed visual assessment and quantitative analysis of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) for MGCTs. A total of 35 MGCT patients (age = 33.1 ± 16.8 years, F:M = 16:19) who underwent preoperative PET/CT were retrospectively reviewed. The pathologic diagnosis of MGCTs identified 24 mature teratomas, 4 seminomas, 5 yolk sac tumors, and 2 mixed germ cell tumors. Visual assessment was performed by categorizing the uptake intensity, distribution, and contour of primary MGCTs. Quantitative parameters including the maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter were compared between benign and malignant MGCTs. On visual assessment, the uptake intensity was the only significant parameter for differentiating between benign and malignant MGCTs (p = 0.040). In quantitative analysis, the SUVmax (p < 0.001), TBR (p < 0.001), MTV (p = 0.033), and TLG (p < 0.001) showed significantly higher values for malignant MGCTs compared with benign MGCTs. In receiver operating characteristic (ROC) curve analysis of these quantitative parameters, the SUVmax had the highest area under the curve (AUC) (AUC = 0.947, p < 0.001). Furthermore, the SUVmax could differentiate between seminomas and nonseminomatous germ cell tumors (p = 0.042) and reflect serum alpha fetoprotein (AFP) levels (p = 0.012). The visual uptake intensity and SUVmax on [18F]FDG PET/CT showed discriminative ability for benign and malignant MGCTs. Moreover, the SUVmax may associate with AFP levels.

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.

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.

Multimodality treatment outcome in patients with primary malignant mediastinal germ cell tumor in adults.

BackgroundMalignant mediastinal germ cell tumor (MGCT) is rare and has poor outcomes even after multimodality treatment. Data from resource‐poor countries are scarce in the literature.AimsTo evaluate the clinicopathologic features and treatment outcome of primary malignant MGCT at our center.Methods and ResultsSingle institutional data review of patients aged ≥18 years, treated with a diagnosis of malignant MGCT between Nov'2013 and Nov'2019. Risk stratification was done as per International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Patients were treated with platinum based chemotherapy and surgical resection for the residual disease was performed in non‐seminomatous histology.28 patients had MGCT with a median age of 25 years (range:18‐36) and all were male. Seven patients had superior vena cava obstruction (SVCO) at diagnosis and pre‐treatment histological diagnosis was available in 23 (82%) patients. Seven (25%) patients had seminoma histology, all were of good risk as per IGCCCG risk criteria, whereas others had non‐seminoma histology with poor‐risk group. Seven patients with seminoma histology achieved a complete response after initial treatment. Six patients with non‐seminoma histology underwent complete resection of residual disease post‐chemotherapy and five revealed residual viable tumors. After a median follow‐up of 10.8 months (range:2.9‐75), 3‐year progression‐free survival (PFS) and overall survival (OS) estimate was 61.2% and 94.7% in the whole cohort, respectively and 3‐year PFS and OS estimate was 100% in patients with seminoma histology.ConclusionsThis is the largest data set of MGCT patients' outcomes reported from India with multi‐modality treatment. All patients were male and one‐fourth had SVCO at presentation. Seminoma histology patients had a 100% outcome after initial platinum based chemotherapy. But, those with non‐seminoma histology had a poor outcome even with chemotherapy and surgery.

Primary malignant mediastinal germ cell tumors: A single institutional experience.

Background:Primary mediastinal malignant germ cell tumour (PMMGCT) is rare with unsatisfactory prognosis and pose difficulty in management due to lack of guidelines.Methods:All cases of PMMGCT diagnosed and treated between years 2014 to 2018 were retrospectively evaluated for clinico-pathological features, multimodality treatment and follow up.Results:Among a total of five PMMGCT cases, three were seminomatous and two were non seminomatous tumour [Yolk- sac tumour (n-1) and Mixed tumour (n-1)]. Four of these cases were non - metastatic with locally advancement and another one presented with metastasis to supraclavicular lymph node. All patients received platinum based induction chemotherapy. Post-induction chemotherapy, two cases of non seminomatous tumours underwent surgery. Among the three seminoma cases, one patient showed complete metabolic response; one with metastasis succumbed to the disease and the in-operable case of seminoma received local radiotherapy.Conclusion:PMMGCT needs a multi-disciplinary approach for appropriate diagnosis and management. Clinicopathological features like tumour site, extension, histopathological type, tumour stage and serum tumour marker are necessary for prognostication and decision making of further treatment plan.

Clinical and radiographic characterization of primary seminomas and nonseminomatous germ cell tumors.

Primary malignant mediastinal germ cell tumors (PMMGCTs) including seminomas and nonseminomatous germ cell tumors (NSGCTs) are rare, and sometimes the diagnosis is very difficult. The purpose of this study is to compare the clinical characteristics, biomarkers, and imaging findings of seminomas and NSGCTs and to determine whether these features could help distinguish these two types of PMMGCT. A retrospective study of 24 male patients with histopathologically proven PMMGCT was performed. We collected the information of computed tomography (CT) (the scan area ranged from the apex of lung to the costophrenic angles) and magnetic resonance imaging blood test and histology characteristics of these patients. Twelve of 24 cases were confirmed to be seminomas, whereas the other 12 cases were NSGCTs. Alfa-fetoprotein (AFP) was found to be elevated in all patients with NSGCT, whereas none of the patients with seminomas had elevated AFP level. Beta-human chorionic gonadotropin (β-HCG) level was elevated in all the patients with seminomas (seven/seven), whereas in NSGCT only two of seven patients had elevated β-HCG. Lactate dehydrogenase level was increased in five of the nine patients with seminomas, as well as in the eight patients with NSGCT. CT imaging revealed that 12 masses from the seminoma group were homogeneous, soft tissue opacity and showed minimal contrast enhancement. On the contrary, all 12 NSGCT cases showed cystic and solid masses; on contrast-enhanced CT, heterogeneous enhancement was found on the capsule of the tumor, septum, and solid masses. Seminomas and NSGCT showed different profiles of tumor biomarkers and radiographic features. Evidence from serum test, histopathological analysis, and imaging should be combined to ensure the accurate diagnosis of these two types of PMMGCT.

Primary malignant mediastinal germ cell tumor in childhood

Primary malignant mediastinal germ cell tumor in childhood

Thoracoscopic Repair for Postoperative Chylothorax Using Tissue Sealing Sheet, Polyglycolic Acid Sheet, and Fibrin Glue in a Boy With Malignant Mediastinal Germ Cell Tumor

Thoracoscopic Repair for Postoperative Chylothorax Using Tissue Sealing Sheet, Polyglycolic Acid Sheet, and Fibrin Glue in a Boy With Malignant Mediastinal Germ Cell Tumor

Medical image of the week: fast-growing primary malignant mediastinal mixed germ cell tumor

Medical image of the week: fast-growing primary malignant mediastinal mixed germ cell tumor

Role of post-chemotherapy radiation in the management of children and adolescents with primary advanced malignant mediastinal germ cell tumors.

ObjectivePrimary malignant mediastinal germ cell tumors (MMGCTs) are rare in children and adolescents and have a poorer prognosis than their gonadal counterparts. We report a single institutional experience of a 10-year period of primary advanced MMGCTs treated with chemotherapy, followed by radiotherapy in those who had residual mass.MethodsChildren and adolescents with primary advanced MMGCTs between 2005 and 2014 were identified from the Cancer Center, Sun Yat-Sen University. Medical records were reviewed for clinicopathological characteristics, treatments, and outcomes.ResultsTwenty-four children and adolescents with either stage III or IV primary advanced MMGCTs met the inclusion criteria. There were 23 males and one female with a median age of 16 (range 10–18). Seven cases were seminomas (29.2%); four (16.7%) yolk sac tumors (YST); three (12.5%) choriocarcinomas; and ten (41.6%) nonteratomatous combined germ cell tumors (CGCTs). All patients were treated with first-line cisplatin-based chemotherapy regimens (PEB: 19, VIP: 5). Thirteen (54.2%) and Twelve (50%) patients received surgery and radiotherapy, respectively. With a median follow-up of 46.2 months (range 9.6–124.8 months), a total of five (20%) patients died of disease progression; the five-year overall survival (OS) and disease-free survival (DFS) rates were 82.3% and 64.9%, respectively.—Seven patients with seminoma GCTs received post-chemotherapy irradiation were alive with sustained CR (5-year OS and DFS, 100%, respectively). Five patients with NSGCTs were administered irradiation and one relapsed 35 months later and died of metastasis (5-year OS, 100%; 5-year DFS 66.7%). Univariate analysis identified histology and stage were prognostic factors.ConclusionMultimodality treatment approach of chemotherapy followed by radiation consolidation ensured long-term survival in primary advanced MMGCTs. Further research is warranted to improve the prognosis of children with primary advanced MMGCTs.

Primary Malignant Mediastinal Germ Cell Tumors

Primary malignant mediastinal germ cell tumors are the most common extragonadal germ cell tumors in young adults (PMMGCT). We review in our report the clinical features and therapeutic strategies and outcome of three patients diagnosed with PMMGCT at the department of medical oncology at Hassan II University Hospital of Fez, Morocco and we review briefly the existing literature data.

Long-term outcomes of pediatric and adolescent mediastinal germ cell tumors: a single pediatric oncology institutional experience.

To evaluate the epidemiologic, demographic, and clinical characteristics, as well as prognostic factors and long-term outcomes of mediastinal germ cell tumors (MGCT) in children. A retrospective study of pediatric patients diagnosed with a primary MGCT between January 1963 and August of 2014 was performed. Twenty-five patients were identified. Six children with teratomas were treated with resection alone (median age 7.8years, range newborn to 15years) and were cured without recurrence or progression. Nineteen children were treated for a malignant MGCT (median age 11.7years, range 7months-18years); 5year overall survival (OS) was 0.39±0.12. For malignant non-seminomatous mediastinal germ cell tumors, platinum-based chemotherapy regimen (OS 0.56 vs 0.14, p=0.03), complete surgical resection with negative margins (OS 0.73 vs 0.11, p=0.03); and localized disease (OS 0.76 vs 0.0, p=0.004) demonstrated a survival advantage. Initial surgical resection is appropriate for teratomas. Localized disease, complete resection, and platinum-based chemotherapy are associated with improved survival in malignant non-seminomatous mediastinal germ cell tumors. Neoadjuvant, platinum-based three drug regimens followed by delayed surgical resection is the appropriate treatment modality for malignant mediastinal germ cell tumors.

Clinicopathological features and management of patients with primary malignant mediastinal germ cell tumor: 10 year’s experience in Peruvian patients.

e13088Background: Primary malignant mediastinal germ cell tumor (PMMGCT) are rare and have poor prognosis with particularly different biology from those of other germ cell tumor. The aim of this study was to evaluate the clinicopathological features, different types of treatment response and survival these patients. Methods: Forty-six patients with PMMGCT who were treated at the Instituto Nacional de Enfermedades Neoplasicas, from 2003 to 2012. Overall survival (OS) curves were estimated using the Kaplan-Meier method and comparisons were done using the log-rank test. A p-value < 0.05 was considered statistically significant. Results: Forty-six men and 2 women with a median age of 23 [range: 3-68] were identified, of whom 17 (35.4%) had pure seminoma, 11 (22.9%) had non-seminomatous, 11 (22.9%) had mixed histology and 9 (18.8%) were not determined of histologic type. Thirty-one (64.6%) had tumor located at mediastinum, 7 (14.6%) had lung metastases and /or effusion and 10 (20.8%) had distant metastases. Th...

Role of radiotherapy in treating patients with primary malignant mediastinal non-seminomatous germ cell tumor: A 21-year experience at a single institution.

BackgroundThe aim of this study was to investigate the clinical characteristics and outcomes of patients with primary malignant mediastinal non-seminomatous germ cell tumor (MMNSGCT) by comparing the efficacies of different treatment modalities.MethodsThe charts of 62 consecutive patients with MMNSGCT between 1990 and 2010 were reviewed. Analyses included Kaplan-Meier survival and Cox multivariate regression.ResultsThere was sufficient data of 61 patients for inclusion in the study. The median age was 25 years. At diagnosis, 35 patients had tumors located in the mediastinum, 26 had lung and/or distant metastases. At a median follow-up of 47.2 months, 32 patients had died and 43 had developed progressive disease. The one, three, and five-year overall survival (OS) and progression-free survival (PFS) rates were 72.1%, 50.8%, 49.2% and 47.5%, 32.8%, 32.8%, respectively. Patients who received radiotherapy in the primary treatment regimen showed improved five-year OS (68.2% vs. 38.5%, P = 0.043), PFS (45.5% vs. 20.5%, P = 0.023), and local recurrence-free survival (LRFS) (77.3% vs. 38.5%, P = 0.003) compared with those who did not receive radiotherapy. Multivariate analysis revealed that radiotherapy was an independent prognostic factor of five-year OS (hazard ratio [HR] 0.39, P = 0.037), PFS (HR 0.42, P = 0.017), and LRFS (HR 0.31, P = 0.019).ConclusionRadiotherapy in a chemotherapy-based treatment regimen could significantly reduce local recurrence and improve survival of MMNGCT patients.

Prognostic factors in children with extracranial germ cell tumors treated with cisplatin-based chemotherapy

PurposeTo evaluate the outcomes and prognostic factors in children with extracranial germ cell tumors (GCTs) treated at a single institution.MethodsSixty-six children diagnosed with extracranial GCTs between 1996 and 2012 were included in the study. Primary treatment was surgical excision, followed by six cycles of cisplatin-based chemotherapy. The survival rates were compared according to the International Germ Cell Cancer Cooperative Group classification used for GCTs in adults to validate the classification guidelines for GCTs in children.ResultsThe median patient age was 4.4 years. In 34 patients (51.5%), the primary tumor site was the gonad. Extragonadal GCTs were detected in 32 patients. The 5-year overall survival and event-free survival (EFS) were 92.0%±3.5% and 90.4%±3.7%, respectively. In univariate analysis, tumor histology, metastasis, and elevated alpha-fetoprotein were not prognostic factors in children with extracranial GCTs. However, EFS was poorer in patients with mediastinal disease (n=12, 66.7%±13.6 %) than in those with nonmediastinal disease (n=54, 96.0%±2.8%) (P=0.001). The 5-year EFS was lower in patients older than 10 years, (n=21, 80.0%±8.9%) compared with those younger than 10 years (n=45, 95.2%±3.3%) (P=0.04). Multivariate analysis identified the mediastinal tumor site as the only independent prognostic factor.ConclusionThe prognosis of children with extracranial GCTs was favorable. However, nongerminomatous mediastinal tumors were associated with poor survival in children. Further research is needed to improve the prognosis of children with malignant mediastinal GCTs.

Management of the primary malignant mediastinal germ cell tumors: experience with 54 patients

BackgroundPrimary malignant mediastinal germ cell tumor (PMMGCT) is rare and sometimes the prognosis of the patients with PMMGCT is not very satisfactory.MethodsA total of 54 patients with PMMGCT in a follow-up from 1990 to 2009. We evaluated the role of the surgical treatment and the effect of multimodality treatment strategy for patients with PMMGCT.ResultsFifty-two patients underwent surgical resections, while the other two patients just received chemoradiotherapy. Among the 52 patients, 28 cases received preoperative adjuvant therapy and 24 cases underwent surgery as initial treatment; 30 cases with complete resections, 18 cases with partial resections and 4 cases with only biopsies. There was no perioperative mortality. Histopathologic results revealed 18 cases of seminomas and 36 cases of nonseminomatous germ cell tumors (NSGCT). The last follow-up showed that 17 patients were alive, including 11 patients with seminoma and 6 patients with NSGCT. The 5-year overall survival rate of patients with seminomas was 87.7%. The 3-year and 5-year overall survival rates of patients with NSGCT were 47.4% and 23.0%, respectively.ConclusionsIt could be concluded that a complete surgical resection of PMMGCT after chemoradiotherapy showed favorable long-term survival. Patients with pure seminomas have a better prognosis compared with that with NSGCT.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1676987232116837.

Malignant mediastinal germ cell tumors: Clinical findings and diagnostic and therapeutic problems

縦隔悪性胚細胞性腫瘍（MGCT）の診断および治療アプローチを再確認するために，切除例の検討を行い，臨床上の問題点を明らかにした．対象は，1993～2006年に昭和大学関連3病院で切除したMGCT8例で，21～69歳，すべて男性．部位は前縦隔6例，中縦隔2例．AFP高値2例，HCG高値1例，両マーカーとも高値1例，上昇なし4例であった．組織検査は，CT下針生検4例，傍胸骨生検1例，縦隔鏡1例，未施行2例で，生検を行った6例中5例で，最終病理と一致した．初回治療は，化療4例（CR2例，PR2例），放治1例（NC），手術3例で，最終病理診断は，Seminoma3例，Yolk sac tumor1例，Adenocarcinoma with teratoma1例，Embryonal carcinoma1例，その他2例であった．MGCTの治療に際しては，化療の効果は良好であることからマーカー陽性例は速やかな抗癌剤治療が必要である．MGCTのなかに比較的高齢者，あるいは中縦隔発生例があることは留意すべき点である．

Anterior Mediastinal Tumor

Primary anterior mediastinal neoplasms comprise a diverse group of tumors and account for 50% of all mediastinal masses. Thymic epithelial neoplasm are most common and classified into thymoma, invasive thymoma, and thymic carcinoma. Neuroendocrine differentiation of thymic epithelial neoplasm are rare malignancies. Germ cell tumor (GCT) is second most common anterior mediastinal tumor and most of them are mature cystic teratoma. Malignant mediastinal GCT are rare than benign. Primary thoracic lymphoma is rare than thoracic involvement of systemic lymphoma and most common location of primary thoracic lymphoma is anterior mediastinum. The clinical and radiologic appearance of the most common masses are reviewed.

Primary malignant germ cell tumours

Study objectives : the aim of this enquiry was to perform a retrospective review on patients treated for primary malignant mediastinal germ cell tumours (PMMGCT) between 1992-2008, to specify their clinical characteristics, their prognostic factors and to evaluate the current therapeutic strategies.Patients: we report a study about 8 patients with seminoma in 3 cases, yolk sac tumour (YST) in 2 cases, embryonal carcinoma (EC) in 1 case, choriocarcinoma in 1 case and teratocarcinoma in 1 case. Pathologic diagnoses were confirmed in all cases by surgical biopsy and a resection of the residual mass in 2 cases.Results: all the patients were male with a mean age of 32 years (range, 16 to 63 years). Only one patient was asymptomatic. The most frequent symptoms were cough (87.5%), chest pain (50%) and dyspnea (50%). The 8 tumours were located in the anterior mediastinum. One patient with EC didn’t received any treatment because of the rapid evolution of the disease. The 7 others received pre-operative chemotherapy and 3 patients received a second-line chemotherapy because of the persistence of viable tumours in one case (YST) and a resistance to the first chemotherapy in 2 cases (seminoma and teratocarcinoma). The overall 2-year survival of patients with seminoma was 100% towards 25% for those with nonseminomatous tumours. The patients with satge I disease survived for a mean period of 3 years.Conclusion: The PMMGCT cause generally a diagnostic challenge because of the difficulty of their resection and the little size of the biopsy specimen. Besides, the absence of a primary gonadal localization may be difficult to establish. These tumours have a worse prognosis than their gonadal counterparts. Prognostic factors are multiple and not accurate. The most relevant ones seem to be the histological type and the disease stage.

Intracranial germ cell tumors: association with Klinefelter syndrome and sex chromosome aneuploidies

Intracranial germ cell tumors (ICGCTs) occur mainly in male children and adolescents. Polyploidy of the X chromosome and X hypomethylation have been suggested as mechanisms of malignant transformation independently of the histological tumor type. On the other hand, several reports associate these tumors with Klinefelter’s syndrome (KS). Recent reports indicate that KS patients have an increased relative risk for development of malignant mediastinal germ cell tumors and also around 8% of male patients with primary mediastinal tumors have KS. In an attempt to explore the frequency of KS amongst patients with ICGCTs and to confirm the presence of X chromosome polyploidies in these tumors, we studied 13 young male patients with ICGCTs. Paraffin-embedded tumoral and normal tissues were studied by FISH. KS was found in 15% of the cases, demonstrating that this constitutive aneuploidy may be related to carcinogenesis. When tumor and non-tumor tissues were compared, statistically significant X and Y chromosome polyploidies in tumors were revealed. These results emphasize that aneuploidies are involved in ICGCT tumorigenesis.