Primary Mediastinal Germ Cell Tumors Research Articles

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.

Primary Mediastinal Yolk Sac Tumors: An Immunohistochemical Analysis of 14 Cases

Primary mediastinal germ cell tumors are uncommon tumors that can pose diagnostic difficulties due to their morphologic spectrum and unusual site. Immunohistochemistry plays an increasing role in the diagnosis of these tumors. Whereas the immunophenotype of testicular yolk sac tumors (YST) is rather well known, the opposite is true for primary mediastinal YST leading us to investigate the immunohistochemical features of 14 such neoplasms. Fourteen cases of primary mediastinal YST were reviewed and representative whole tissue sections were selected for immunohistochemical analysis using antibodies directed against CAM5.2, SALL4, OCT3/4, glypican-3, CD30, α-fetoprotein (AFP), CD117, placental alkaline phosphatase (PLAP), GATA-3, and CDX2. The percentage of positive tumor cells and the intensity of staining were evaluated and scored. All cases (100%) showed strong and diffuse expression of CAM5.2 and SALL4, 10 cases (71%) reacted with glypican-3 and AFP in a patchy manner, 5 cases (36%) showed focal positivity with PLAP and GATA-3, 4 cases (29%) showed staining for CDX2, 3 (21%) showed expression of CD117, and a single case was positive for CD30 (7%). None of the cases showed any staining for OCT3/4. Primary mediastinal YST appear to have a similar immunohistochemical phenotype as their testicular counterparts. Coexpression of CAM5.2, SALL4, glypican-3, and AFP provides the best support for YST differentiation; however, it has to be noted that none of these markers is specific for these tumors and immunohistochemical results will always have to be interpreted in the context of morphologic, clinical, and radiologic information.

Clinical Characteristics and Treatment Outcomes of Patients with Primary Mediastinal Germ Cell Tumors: 10-Years' Experience at a Single Institution with a Bleomycin-Containing Regimen

Background: Cisplatin-based chemotherapy followed by surgical resection of the residual tumor remains the standard of care for patients with mediastinal germ cell tumors (MGCTs). To prevent pulmonary complications, a non-bleomycin-containing regimen is generally preferred. This study aims to review the clinical characteristics and outcomes of these patients. Methods: A retrospective chart review was undertaken in patients treated for MGCTs between 2003 and 2013. Results: A total of 40 patients were enrolled; 7 patients were diagnosed with seminoma, while 33 patients had non-seminoma. 92% of patients received chemotherapy as a first treatment modality: 87% bleomycin, etoposide and cisplatin; 13% etoposide and cisplatin, with an objective response rate of 61.3%. Among these, 44% achieved a complete serological response. 17 patients underwent surgical resection of the residual tumor. No patient suffered from pulmonary complications after surgery. The 5-year overall survival (OS) was 71.4 and 27.3% in seminoma and non-seminoma patients, respectively (p = 0.051). For those who received chemotherapy followed by surgical resection with no viable tumor or only mature teratoma detected, the 5-year OS was 72.7% compared with 20.7% in patients not treated with surgery (p = 0.02). Conclusion: Our study confirmed the importance of a multimodality approach with primary chemotherapy followed by surgical resection of the residual tumor. A bleomycin-containing regimen can be safely used in this setting.

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...

Myelodysplastic Syndrome (RAEB-II) Development 2 Months after Chemotherapy for a Primary Non-seminomatous Mediastinal Germ Cell Tumor

Myelodysplastic Syndrome (RAEB-II) Development 2 Months after Chemotherapy for a Primary Non-seminomatous Mediastinal Germ Cell Tumor

Primary mediastinal non-seminomatous germ cell tumour in a young female

Primary mediastinal non-seminomatous germ cell tumour in a young female

Impact of bleomycin (BLM) administration on the development of pulmonary toxicity in advanced germ cell tumors (GCT) receiving first-line chemotherapy (CT): A meta-analysis of randomized studies.

482 Background: Little is known about the impact of BLM administration on the development of pulmonary toxicity (PT) in patients (pts) with advanced GCT. This information is critical to further enhance the successful delivery of effective and safe CT in these pts. Methods: Literature was searched for randomized trials of 1st-line CT ( ≥ 3 cycles) for GCT. Descriptive statistics were used to summarize data, dichotomized by BLM-containing vs non containing CT. Univariable and multivariable analyses by random effect models evaluated the predictive role of BLM administration on the development of all grade and G3-4 PT, adjusted for the length of follow-up (FUP, continuous), time-frame of treatment ( ≤ 1997 versus &gt; 1997) % of pts with lung metastases (LM), % of primary mediastinal GCT (PMGCT), IGCCCG risk group. Results: 53 arms of 26 phase II and III trials totalling 6,498 pts were selected: 40 with BLM (n = 5,093) and 13 without BLM (n = 1,405). Median % of pts with LM was 44% (range 22-84%) and 31% (19-79%) in BLM-containing and non containing arms (Wilcoxon test p = 0.505). Median % of PMGCT was 15% (range 0-48%) and 2% (0-13%), respectively (p = 0.146). Median BLM total dose and No. of administrations were 360mg (range 120-375) and 12 (2-24). Median FUP was 52 and 53 months, respectively. The pooled probability of all grade PT was 11.7% (95% CI: 8.4-16.0%) and 1.7% (95% CI: 0.7-4.2%) in BLM-containing and non containing arms. Univariably, BLM administration was associated with the incidence of both all grade (odds ratio [OR]: 7.57, 95%CI: 2.84-20.18, Wald test p &lt; 0.001) and G3-4 PT (OR: 5.19, 95%CI: 1.57-17.16, p = 0.007). Multivariably, BLM administration was significantly associated with the incidence of all grade PT (OR: 4.14, 95%CI: 1.36-12.59, p = 0.012) and trended to significance for G3-4 toxicity (OR: 2.24, 95%CI: 0.91-5.51, p = 0.080). Conclusions: In this meta-analysis, BLM administration was significantly associated with the development of PT in pts with GCT. The quantification of the magnitude of incidence of PT provided here might be useful to optimize the delivery of non-PEB CT in the 1st-line setting.

Multimodality treatment of primary mediastinal germ cell tumor with growing teratoma syndrome: a case report

Germ cell tumors arise from errors occurring during the migration of embryonic stem cells to the gonads. They constitute 10-15% of malignant mediastinal tumors. Thirty-nine years old male patient was admitted with shortness of breath and gynecomastia. Positron emission tomography / Computed tomography (PET/CT) showed hypermetabolic mediastinal mass in the anterior mediastinum. Serum tumor markers were elevated. Mixed germ cell tumor was diagnosed via transthoracic tru-cut biopsy. After three cycles of systemic cisplatin, etoposide and bleomycin treatment, PET/CT showed a decreased metabolic activity but an increase in the size of mass. Growing teratoma syndrome was diagnosed. The excision of the mass was performed via a median sternotomy. Then autologous stem cell transplantation was performed. Patients was presented as a successful example of a multimodality treatment of a primary mediastinal germ cell tumor with GTS.

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.

Perioperative morbidity and mortality with bleomycin in primary mediastinal non seminomatous germ cell tumor (PMNSGCT).

4538 Background: PMNSGCT represents one of the most challenging subsets of malignant germ cell tumors. PMNSGCT has a distinctly worse prognosis and is appropriately categorized as poor risk disease...

A case of acute megakaryocytic leukemia associated with a nonseminomatous primary mediastinal germ cell tumor diagnosed through elevation of serum lactate dehydrogenase

Introduction: Hematologic malignancies are seen in a small percentage of patients with primary mediastinal germ cell tumors (PMGct). case report: A 29-year-old male patient with a nonseminomatous primary mediastinal germ cell tumor was diagnosed with acute megakaryocytic leukemia. serum lactate dehydrogenase (LDH) elevation was a diagnostic clue. We discussed our case with a review of literature. conclusion: Oncologists should be aware of the association of PMGct with hematologic malignancies and consider this phenomenon as a differential diagnosis when LDH elevation is present in patients with PMGct.

Exuberant Vasculoconnective Component in Mediastinal Mixed Germ Cell Tumors.

We aimed to evaluate the histologic components of primary mediastinal mixed germ cell tumors. A total of 221 patients diagnosed with a mediastinal germ cell tumor (GCT) were retrospectively reviewed. Among them, 14 patients underwent surgical resection after chemotherapy and 8 patients were diagnosed with mixed GCT, who were then selected for further evaluation. Clinical chart review and histologic review of biopsy and surgical specimens of 8 patients were performed. All 8 patients were young males and showed a mature teratoma or a mature teratoma with a focal immature teratoma in the resected specimens. Serum alpha-feto protein was variably elevated. Seven patients experienced an increase in tumor size after the chemotherapy. In 5 patients, a variable amount of vasculoconnective tissue was found along with the mature teratoma occupying average 66.3% of resected mass, and 3 of them showed an identical vasculoconnective component on biopsy before chemotherapy. We suggest that vasculoconnective tissue might be the intrinsic component of primary mediastinal mixed GCT. When vasculoconnective tissue is obtained on small biopsy of an anterior mediastinal mass of a young male, the possibility of underlying mixed GCT should be considered and further clinical work up should be performed.

Primary non seminomatous germ cell tumour with liver metastasis

Introduction Categorised as poor-risk disease, primary mediastinal non-seminomatous germ cell tumours (PMNSGCT) with metastasis have a dismal survival rate.

A Prognostic Model Including Pre- and Postsurgical Variables to Enhance Risk Stratification of Primary Mediastinal Nonseminomatous Germ Cell Tumors: The 27-Year Experience of a Referral Center

BackgroundPrimary mediastinal germ cell tumors (PMGCTs) poorly benefit from chemotherapy and half of patients die because of disease progression. Enhancing the risk stratification might result in tailoring a more personalized treatment strategy from the time of diagnosis. Patients and MethodsBetween the years 1985 and 2012, 86 patients with PMGCT were treated at our center. Cox proportional hazards regression analysis was conducted in the population of nonseminomas to examine the prognostic effect of candidate factors on progression-free and OS. OS curves were compared using the Kaplan–Meier method and the log-rank test. ResultsMean age was 29.8 years (range, 15-63 years). Twenty-five patients (29.1%) had lung and 8 (9.3%) liver, bone, or brain metastases. Twelve patients (13.9%) received upfront high-dose chemotherapy and 45 patients (52.3%) underwent surgery after chemotherapy. Cox analyses included 61 evaluable primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs). The final model of factors indicating a poor prognosis included the combination of surgery and histological response (overall P = .011) and lung metastases (hazard ratio, 3.03; 95% confidence interval, 1.12-8.15; P = .028). The model showed a bootstrap-corrected Harrel c-statistic for OS of 0.66. A risk stratification model based on the combination of these factors and accounting for a 50% 5-year survival cutoff identified 2 groups (poor prognosis, n = 33 vs. good prognosis, n = 28) with distinct OS curves (P < .001). Preoperative serum tumor marker level was not associated with the final histology (P = .853, χ2 test). Results were limited by small numbers. ConclusionPatients with PMNSGCT included 2 subpopulations with distinct prognosis, and therapeutic improvements are needed for patients with poor-risk features.

Postchemotherapy Surgery for Germ Cell Tumors—What Have We Learned in 35 Years?

Postchemotherapy surgery for advanced testicular cancer has evolved over the last couple of decades. Patients with nonseminomatous germ cell tumors and residual retroperitoneal mass ≥1 cm should undergo postchemotherapy retroperitoneal lymph node dissection (RPLND). For seminoma, RPLND is considered in those patients with masses ≥3 cm that are also positron emission tomography positive. Masses that occur outside of the retroperitoneum should be completely resected with the possible exception of bilateral lung masses when resection of the first mass shows necrosis. The role of surgery in patients with extragonadal germ cell tumors is most vital in those with primary mediastinal nonseminomatous germ cell tumors. Importantly, patient selection, surgical planning, and consideration of referral to centers with this expertise are important to optimize success.

Analysis of Treatment Results in Primary Germ Cell Tumours with Mediastinal Location: Own Experience

Primary germ cell tumours with mediastinal location comprise 1-6% of mediastinal tumours and 2-5% of all germ cell tumours occurring in adults. They are identified mostly in the 3rd decade of life, in 90% of cases in men. The most common symptoms are dyspnea, chest pain, cough, fever and weight loss. The aim of the present study was the analysis of our own results of treatment of primary germ cell tumours with mediastinal location, and a review of the literature concerning this subject. Five patients (4 males, 1 female) median age 27.8 years (range 23-30 years) treated in the period from 1999 to 2009 in Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Lung Cancer and Chest Tumours in Warsaw, due to germinal tumours with primary mediastinal location, entered the study. All patients received chemotherapy according to the BEP regimen. All patients achieved an objective response to treatment. Two patients died due to disease progression in spite of II- and III-line treatment. Three patients are still in follow-up. The median survival time was 55.8 months (range 8.0-120.0 months). Primary mediastinal germ cell tumours have worse prognosis than do those with gonadal location. Based on our observations and review of the literature, it can be concluded that the results of treatment of non-seminoma type germ cell tumours with primary mediastinal location remain poor. Patients who develop early recurrence or progression during first-line chemotherapy are particularly at risk of unfavourable outcome. Identification of new standards of treatment in tumours resistant to cisplatin require further studies evaluating the effectiveness of new generation cytostatic drugs.

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.

Clinical characteristics and outcomes of patients with primary mediastinal germ cell tumors.

389 Background: Mediastinal germ cell tumors (MGCTs) account for 20% of all mediastinal tumors. Cisplatin-based chemotherapy followed by surgical resection of residual tumor remains the standard of care. To prevent pulmonary complications secondary to extensive thoracic surgery, non-bleomycin containing regimen is generally preferred. This study aims to review clinical characteristics and outcomes of these patients. Methods: A retrospective chart review was undertaken in patients with MGCTs treated in our institution between 1993 and 2013. Results: A total of 40 patients were enrolled with a median age of 24. Only one patient is female. Stratified by histology; eight patients (20%) had pure seminoma, 25 patients (62.5%) had pure non-seminoma, four patients (10%) had mixed seminoma and non-seminoma, and three patients (7.5%) had malignant transformation (two adenocarcinoma, one sarcoma). Median tumor size was 13 centimeters. Ninety-two percent of patients received chemotherapy as a first treatment modality, whereas 8% underwent upfront surgery. All patients received cisplatin-based chemotherapy: Eighty seven percent bleomycin, etoposide and cisplatin; 13% etoposide and cisplatin. Seventy-two percent of patients completed four planned cycles of chemotherapy. Thirty-one patients were able to assess radiological response: 3.2% complete response, 58.1% partial response, 29.0% stable disease, and 9.7% progressive disease. Forty-four percent of patients achieved completely serological response with chemotherapy. Seventeen patients underwent surgical resection of residual tumor. Among these, viable tumor was seen in 35% (6 out of 17 patients). No patients complicated with clinically significant pulmonary complications after thoracic surgery. The five year overall survival (OS) of patients with seminoma was 72.9% as compared with 19.9% in those with non-seminoma (p=0.012). For those who received chemotherapy followed by surgical resection with no viable tumor or only mature teratoma detected (N=11), the five year OS was 64.9%. Conclusions: Our study confirmed the importance of multi-modality approaches with primary chemotherapy followed by surgical resection of residual tumor. Bleomycin-containing regimen can be safely used in this setting.

Enhancing risk stratification in primary mediastinal nonseminomatous germ cell tumors (PMNSGCT): A 27-year experience at a tertiary cancer center.

373 Background: Mediastinal GCTs and PMNSGCTs poorly benefit from CT and half of patients (pts) still die for disease. Enhancing the risk stratification may result in tailoring a personalized treatment strategy since diagnosis. Methods: Between 1985 and 2012, 87 pts with PM-GCT were treated at our center. Of them, pure seminomatous histology was excluded. Cox proportional hazards regression analysis was conducted to examine the prognostic impact of these candidate factors on overall survival (OS): type of 1st-line CT (high [HDCT] vs conventional dose [CDCT]), post-CT surgery, type of baseline elevated serum tumor marker (STM), presence of lung or liver-bone-brain metastases (LBB), STM response (still elevated vs normal or normalized), and histology (viable cancer [VC] vs necrosis/teratoma [NT]). OS curves were compared by Kaplan Meier method with the log-rank test. Results: The study included 68 cases with PMNSGCT. Median age was 28.5 yrs (IQR: 23-35). 12 pts (17.7%) presented with mediastinal syndrome, 23 (33.8%) had lung and 7 (10.3%) LBB metastases. 12 pts received upfront HDCT and 45 pts (66.2%) underwent post-CT surgery. The final model of poor prognostic factors included no surgery (HR: 8.74, 95%CI, 1.77-43.01), surgery + VC (HR: 6.97, 95%CI, 1.46-33.30), and lung metastases (HR: 2.92, 95%CI, 0.99-8.64). The model demonstrated moderate discriminatory ability for OS (c-statistic=0.68). A risk stratification model based on the combination of these factors and accounting for a 50% five-year survival cutoff identified 2 groups (poor prognosis, N=28 vs good prognosis, N=26) with distinct overall survival curves (p&lt;0.001). Pre-operative STM and final histology were not associated (p=0.574 at Chi squared test). 5-yr OS after receiving 2nd line CT (n=25) was 18.7% (95%CI, 7.9-44.5). Results are limited by small numbers. Conclusions: Pts with PMNSGCT classified as having a good prognosis in this model had a fairly high survival estimate, while a strategy of consolidation CT for pts with poorest risk features warrants investigation, once the model is confirmed. The effect of surgery on survival was independent of post-CT STM, which also poorly predicted final histology.

High‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation for recurrent primary mediastinal malignant germ cell tumor: A case report

A 15-yr-old boy presented with an anterior mediastinal mass, multiple lung metastases and obstruction of the left brachiocephalic vein, the superior vena cava and the subclavian vein. Tumor biopsy by CT guidance confirmed a diagnosis of GCT. Five courses of BEP therapy were performed, and CT of the chest revealed reduction in the anterior mediastinal mass and disappearance of the multiple lung metastases. We performed the anterior mediastinal mass extraction followed by adjuvant chemotherapy consisting of ICE and TIP. However, the AFP levels became elevated soon after. Abnormal accumulation was observed in the right upper lung by DW-MRI. After the operation, two courses of TI chemotherapy and two courses of HDCT followed by auto-PBSCT were performed. He was complicated with auditory disorder and renal dysfunction. Although HDCT followed by auto-PBSCT was effective for the relapsed primary mediastinal GCT, a treatment strategy avoiding late complications is warranted.