Mediastinal Nonseminomatous Germ Cell Tumors Research Articles

Optimal Treatment Strategies for Early-Stage Primary Mediastinal Germ Cell Tumors

Data on optimal therapy for patients with primary mediastinal germ cell tumors consist overwhelmingly of single-institution studies with small sample sizes. The objective of this study is to assess the association of survival outcomes with surgery vs non-operative management for patients with early-stage primary mediastinal germ cell tumors. Overall survival of all patients with seminomas and non-seminomatous primary germ cell tumors in the mediastinum who received 1) chemotherapy, or 2) surgery with or without chemotherapy (referred to as 'surgery' for simplicity) for early-stage disease from 2004-2015 in the National Cancer Database was assessed using Kaplan-Meier analysis, propensity score-matched analysis, and multivariable Cox proportional hazards analysis. Among patients with seminomas, chemotherapy alone was used in 120 (80.5%) patients and surgery was used in 29 (19.5%) patients. There was no significant difference in 5-year survival between surgery and chemotherapy in unadjusted and propensity score-matched analysis. Among patients with non-seminomatous tumors, chemotherapy alone was used in 91 (46.7%) patients and surgery was used in 104 (53.3%) patients. Surgery was associated with improved 5-year survival when compared to chemotherapy in unadjusted, and multivariable-adjusted, and propensity score-matched analysis. In this national analysis, multimodality treatment involving surgery was associated with improved survival when compared to chemotherapy alone for early-stage primary mediastinal non-seminomatous germ cell tumors. For seminomas of the mediastinum, chemotherapy was associated with similar long-term outcomes when compared to multimodality treatment involving surgery.

High-dose chemotherapy and peripheral blood stem cell transplantation as salvage therapy in primary mediastinal nonseminomatous germ cell tumors: The Indiana University experience.

Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high-dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University. The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first-line cisplatin-based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and 750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression-free survival and overall survival were analyzed using the Kaplan-Meier method. Medians with 95% confidence intervals were also calculated along with 2-year probabilities. The median age at HDCT was 30 years (range, 18-61 years). With a median follow-up of 4.7 years (range, 1-14 years), the 2-year progression-free survival rate was 31% (95% confidence interval, 16%-47%), and the 2-year overall survival rate was 35% (95% confidence interval, 19%-52%). At last follow-up, nine patients (28%) remained without evidence of disease, including two platinum-refractory patients and two patients who were receiving HDCT as third-line therapy. There were three treatment-related deaths. Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum-refractory and third-line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population.

Extragonadal germ cell tumors: A clinicopathologic study with emphasis on molecular features, clinical outcomes and associated secondary malignancies

Extragonadal germ cell tumors (EGCTs) are rare, representing <5% of all germ cell tumors (GCTs). Whilst EGCTs share morphological and immunohistochemical features with their gonadal counterparts, they tend to be more aggressive and are frequently associated with secondary somatic malignancies. The aim of our study was to evaluate the clinical, morphological and immunohistochemical features, and to analyze tumors for chromosomal abnormalities of 12p, in addition to any novel genetic alterations, in a series of EGCTs. Seventy-seven EGCTs were included. Anterior mediastinum was the most common anatomic site, followed by central nervous system, retroperitoneum, sacroccygeal area, and neck. Whole genome SNP array identified isochromosome 12p in 26% of tumors. Additional cytogenetic abnormalities included the presence of gain of chr 21 in 37% of tumors. Somatic-type malignancies were identified in 8% of patients. Disease progression (metastasis and/or recurrence) was documented in 8 patients, most of whom died from their relapse. Three patients who died of disease had somatic-type malignancies. Mediastinal seminomas had a significantly better overall survival when compared to mediastinal non-seminomatous GCTs. Our study demonstrates that EGCTs share similar histologic features, but diverse clinical outcomes compared to their gonadal counterparts. Outcomes vary according to anatomic location and histologic subtypes. Our data corroborate that somatic-type malignancies are frequently encountered in mediastinal EGCTs and that their presence portends a poorer prognosis.

Malignant Teratoma Arising From Mediastinal Non-Seminomatous Germ Cell Tumor: A Rare Case Report

Introduction: Primary mediastinal non-seminomatous germ cell tumors (NSGCT) have a worse prognosis than gonadal germ cell tumors (GCTs). Malignant transformation of teratomatous components of GCT to a somatic malignancy is rare.&#x0D; Materials and methods: A case of primary mediastinal NSGCT with malignant transformation of a teratoma was seen in a 23 years old male. Resected tumor specimen was received. Tissue processing was done and sections were prepared for Histo Pathological Examination.&#x0D; Results: Histopathology confirmed NSGCT with yolk sac and teratomatous components. Chemotherapy for GCT transiently normalized serum tumor markers with little effect on the mediastinal mass. Incomplete resection of the residual tumor revealed intermediate grade chondosarcoma. Here we discuss this rare case.&#x0D; Conclusion: malignant transformation to chondrosarcoma is a rare possibility which needs to be considered while managing the patient of Primary Mediastinal Germ Cell Tumors (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.

Salvage high-dose chemotherapy (HDCT) for relapsed primary mediastinal nonseminomatous germ-cell tumors (PMNSGCT).

5032 Background: Patients with PMNSGCT have high relapse rates after first-line therapy. Historical outcomes in this subset with standard-dose salvage chemotherapy or HDCT+bone marrow transplant (BMT) have been poor. The use of peripheral-blood stem-cell transplant (PBSCT) has allowed for more rapid engraftment and the ability to start the 2nd course 3-4 weeks after the 1st course of HDCT. We report survival outcomes of salvage HDCT+PBSCT in relapsed PMNSGCT. Methods: Between 2004-January 2021, 32 pts with relapsed PMNSGCT were treated with HDCT+PBSCTx2 utilizing our institutional regimen: carboplatin 700 mg/m2 + etoposide 750 mg/m2, for 3 consecutive days, followed by PBSCT. Median time between cycle1 day1 to cycle2 day1 was 3.2 wks (range, 2.6-4.6). Kaplan-Meier methods were used for progression-free (PFS) and overall survival (OS) analysis. Results: Median age was 30. At the start of HDCT, median AFP was 192 (range, 4-17130) and hCG 1.5 (range, 0.6-15711). First-line therapy was standard germ cell tumor chemotherapy such as bleomycin-etoposide-cisplatin (BEP) or etoposide-ifosfamide-cisplatin (VIP). HDCT was 2nd line in (26, 81.3%) and 3rd line in (6, 18.8%). Eighteen (56.3%) pts had platinum-refractory disease defined as progression within 4 weeks of 1st line chemo. Twenty-three (72%) patients had extra mediastinal metastases (mets) at the start of HDCT. Metastatic sites included pulmonary (17), lymph nodes (2), liver (3), bone (2), brain (1). Median follow-up time from start of HDCT was 1 yr (range, 0.02-14.1). Twenty-six (81%) pts completed both cycles, while 6 (19%) completed only one cycle due to toxicity or progression. The estimated 2-yr PFS was 30.7 (95% CI, 15.8-46.9) and 2-yr OS was 35.2 (95% CI, 18.9-51.9). At the most recent follow-up, 9 (28%) pts were continuously no evidence of disease (NED), including 2 pts who had surgical resection of teratoma following HDCT. Median follow-up from the start of HDCT for the NED pts was 4.6 yrs (range, 1-14.1). Five of the NED pts had extra mediastinal mets, and 2 had platinum-refractory disease. Among the 9 NED pts, HDCT was 2nd line in 7 (77.8%) and 3rd line in 2 (22.2%). These results compare favorably to historical data with standard-dose chemotherapy or HDCT+BMT in relapsed primary mediastinal GCT with salvage rates &lt; 10% (Hartmann et al., JCO 19:1641-1648, 2001). Grade ≥3 toxicity, as previously described in our study (Adra et al., JCO 35:1096-1102, 2017), occurred in 8 (25%) pts. There were two treatment-related deaths. Conclusions: HDCT+PBSCT is a safe and effective salvage therapy in pts with relapsed PMNSGCT with curative potential. In our opinion, these complicated patients are best managed at tertiary centers with expertise in medical oncology, stem cell transplantation, and thoracic surgical oncology.

Peri-treatment adverse events of primary mediastinal non-seminomatous germ cell tumors.

Primary mediastinal non-seminomatous germ cell tumors (PMNSGCT) are rare but life-threatening thoracic cancers. We report our experience from eight patients with peri-treatment adverse events. By analyzing changes in tumor extent, serum tumor markers, and pathologies between diagnosis and transfer, those events could be attributed to postbiopsy respiratory insufficiency, growing teratoma syndrome, secondary histiocytic malignancy, and PMNSGCT progression. Subjecting patients to respiratory therapy, conventional or high-dose chemotherapy, and surgery controlled the disease, with five of the eight patients surviving disease free. These outcomes indicate that integrated appropriate and timely approaches are important in tackling peri-treatment adverse events.

Survival Outcomes of Patients With Primary Mediastinal Germ Cell Tumors: A Retrospective Single-institutional Experience

Primary mediastinal non-seminomatous germ cell tumors (PMNSGCTs) are occasionally complicated by a hematologic malignancy, as with somatic-type malignant tumors called germ cell tumors with somatic-type malignancy (GCTSTM) and are known to have a poor prognosis. Data obtained between September 1997 and February 2020 for patients with mediastinal germ cell tumor at our institution were retrospectively analyzed. Key outcome measures included survival rates and the clinical features of non-seminoma cases. Of 16 patients, 9 had pure seminoma, and 7 had non-seminoma. At the median follow-up of 56.2 months, the 5-year survival rate was significantly higher in patients with seminoma (100%) than in those with non-seminoma (37%) (log-rank test, p=0.0153). Regarding PMNSGCT, two patients evolved into GCTSTM and three had concomitant hematological malignancies. Patients with PMNSGCTs, GCTSTM complications, and hematologic malignancies showed poor survival, suggesting the need for the development of treatment strategies.

Primary mediastinal germ cell tumours: real world experience in the low middle income (LMIC) setting.

PurposePrimary mediastinal germ cell tumours (PMGCTs) are rare; with limited data available about their outcomes and optimal treatment in the low middle income countries setting. We studied the clinical profile of patients with PMGCT treated at our centre in order to estimate their survival outcomes and to identify prognostic factors affecting the same.Patients and methodsFifty-seven patients with PMGCTs treated between April 2001 and June 2019 were included. Baseline characteristics, details of first line chemotherapy, response rates, toxicity and surgical outcomes were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsAmong 57 male patients (seminoma = 20 and nonseminomatous = 37), the median follow-up was 10 months (range: 1–120 months). For mediastinal seminoma, 9 (45%) and 11 (55%) patients had good and intermediate risk disease, respectively. Nineteen patients (95%) received BEP (Bleomycin, etoposide and cisplatin) chemotherapy. 94.7% had partial responses and median event-free survival was not reached. All patients were alive and disease free at 2 years. For primary mediastinal nonseminomatous germ cell tumours (PMNSGCTs), all patients were poor risk. Thirty-four (91.8%) received BEP/EP chemotherapy as first line. Responses were PRM+ (partial response with elevated markers) in 7 (20.5%) and PRM− in 12 (35.2%). The incidence of febrile neutropenia was 50% and 55.8% in seminole and PMNSGCT, respectively. The median OS was 9.06 months and median PFS was 4.63 months for PMNSGCT. The proportion of patients alive at 1 year and 2 years were 35% and 24.3%, respectively.ConclusionPrimary mediastinal seminomas are rarer and have better survival outcomes. Treatment of PMNSGCT is still a challenge and is associated with poorer survival outcomes.

Histiocytic sarcoma following combination chemotherapy for primary mediastinal germ cell tumor: a diagnostic dilemma.

Histiocytic sarcoma is considered an extremely rare condition. We herein report on a case of histiocytic sarcoma following combination chemotherapy for a primary mediastinal germ cell tumor in a 26-year-old Asian man who visited the General Medicine Department of a hospital with complaints of cough and high fever. Chest computed tomography (CT) imaging revealed a tumor (diameter 10.5cm) in the anterior mediastinum, with no signs of metastasis, and CT-guided biopsy of the mediastinal tumor revealed the presence of some necrotic cartilages. The patient's serum α-fetoprotein (AFP) level was determined to be high at 160.4ng/mL and a primary mediastinal non-seminomatous germ cell tumor was suspected, so the patient was referred to the Department of Urology. Despite the presence of severe thrombocytopenia, the patient was treated using a combination of chemotherapy and intermittent transfusion, which was able to normalize his serum AFP level. However, resection of the mediastinal tumor was unsuccessful due to persistent thrombocytopenia and the patient was subsequently transferred to our hospital for further examination and treatment. Despite management by hematologists, the condition of the patient did not improve; although his AFP level remained normal, the tumor increased in size and then metastasized to the liver and spleen. The general condition of the patient deteriorated and he died 9months after his first visit. The patient was diagnosed with histiocytic sarcoma following a pathological autopsy. Due to the extremely rare incidence of histiocytic sarcoma, this condition should be a differential diagnosis and the appropriate tests must be conducted to give an exact treatment.

Germ cell tumors and associated hematologic malignancies evolve from a common shared precursor.

Germ cell tumors (GCTs) are the most common cancer in men between the ages of 15 and 40. Although most patients are cured, those with disease arising in the mediastinum have distinctly poor outcomes. One in every 17 patients with primary mediastinal nonseminomatous GCTs develop an incurable hematologic malignancy and prior data intriguingly suggest a clonal relationship exists between hematologic malignancies and GCTs in these cases. To date, however, the precise clonal relationship between GCTs and the diverse additional somatic malignancies arising in such individuals have not been determined. Here, we traced the clonal evolution and characterized the genetic features of each neoplasm from a cohort of 15 patients with GCTs and associated hematologic malignancies. We discovered that GCTs and hematologic malignancies developing in such individuals evolved from a common shared precursor, nearly all of which harbored allelically imbalanced p53 and/or RAS pathway mutations. Hematologic malignancies arising in this setting genetically resembled mediastinal GCTs rather than de novo myeloid neoplasms. Our findings argue that this scenario represents a unique clinical syndrome, distinct from de novo GCTs or hematologic malignancies, initiated by an ancestral precursor that gives rise to the parallel evolution of GCTs and blood cancers in these patients.

Abstract 5169: Tissue analysis of NAD(P)H: quinone oxidoreductase (NQO1) and catalase expression in patients with germ cell tumors (GCT)

Abstract Background: Testicular germ cell tumor (GCT) is the most common cancer in young men between 15 and 35 years of age. Cisplatin-based combination chemotherapy will cure 70% of patients with metastatic GCT. Patients who relapse can still be cured with salvage standard-dose or high-dose chemotherapy. However, about 15% of patients with relapsed/refractory GCT are incurable. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a two-electron oxidoreductase elevated in several tumor types compared to normal tissue. NQO1 detoxifies quinones and reduces oxidative stress. NQO1 bioactivatable drugs induce DNA damage in cells overexpressing NQO1, but not in cells lacking it, hence delivering tumor-selective damage and cell death. Alterations in catalase expression can cause cytoprotection. The ratio of NQO1:catalase activities is presumed to be a predictive marker for therapeutic activity of NQO1 bioactivatable drugs. There is no existing data on NQO1 or catalase expression in GCTs. Methods: Patients with testicular or extra-gonadal GCT who had surgery between January 2016 and December 2018 were identified from the Indiana University Melvin and Bren Simon Cancer Center Tissue Bank database. Patients with non-seminomatous GCT (NSGCT) of testis or primary mediastinal NSGCT were selected and specimens obtained. Immunohistochemistry staining was performed on tumor tissue to determine the quantity and intensity of NQO1 and catalase expression. Results: NQO1 and catalase expression were determined in 16 patients. Thirteen specimens stained moderately to strongly positive for NQO1. Only 1 specimen stained negative. Conversely, no specimen stained strongly positive for catalase, and only 2 stained moderately positive. Fourteen specimens were catalase deficient or only mildly positive for catalase. The details of the immunostaining is summarized in the table below. Immunohistochemistry staining for NQO1 and catalase in GCTImmunostainNegative(0)Mildly positive (&amp;lt;10%)Moderately positive (10-50%)Strongly positive (&amp;gt;50%)NQO1Quantity01114Intensity0547Combined score1267CatalaseQuantity3472Intensity31120Combined score7720 Conclusions: NSGCTs appear to have high levels of NQO1 and deficiency of catalase. NQO1 bioactivatable agents could serve as a potential therapeutic approach in patients with refractory testicular GCTs. Citation Format: Neda Hashemi Sadraei, Nabil Adra, Constance Temm, Kenneth A. Kesler, Muhammad T. Idrees, David A. Boothman, Lawrence Einhorn. Tissue analysis of NAD(P)H: quinone oxidoreductase (NQO1) and catalase expression in patients with germ cell tumors (GCT) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5169.

Response to guadecitabine (SGI-110) combined with cisplatin and gemcitabine (GCG) in platinum refractory germ cell tumors (GCTs).

e17057 Background: Treatment options for platinum refractory GCTs are limited. Platinum resistance derives, in part, from tumour suppressor gene promotor methylation. In vitro, this reverses on co-administration of a DNA hypomethylating agent. Guadecitabine is a next generation hypomethylating agent. SPIRE is a phase Ib/IIa clinical trial to establish a GCG dose/schedule. Methods: We report 2 platinum refractory GCT patients (pts) treated (txd) in SPIRE with GCG (guadecitabine 20 mg/m2, SC, day (D) 1-5; cisplatin 70 mg/m2, IV, D8; gemcitabine 1000 mg/m2, IV, D8 + 15; filgrastim 300 μg, SC, D15-21; q21). Results: Pt 1: 21 yo man, testicular mixed GCT (seminoma/malignant teratoma intermediate). Prior tx: 2001, orchidectomy; 2005, 3 x BEP (bleomycin, etoposide, cisplatin) + retroperitoneal lymph node dissection. 2015, 2 x TI (paclitaxel, ifosfamide), 3 x TIP (cisplatin, ifosfamide, paclitaxel); 2016, 3 x HDCE (high dose carboplatin/ etoposide + autologous stem cell transplantation); 2017, 6 x GOP (gemcitabine, oxaliplatin, paclitaxel). In 2017, received 6 x GCG in SPIRE for CT confirmed lung metastases (mets) and rising β-hCG (human chorionic gonadotropin). Response: RECIST stable disease with metabolic CR on PET in lungs and &gt; 90% β-hCG reduction. In Cycle 6, pt developed symptomatic brain mets, treated with WBRT (40Gy, 20#) + cyberknife to the six mets completed 2018. Since 2018, ongoing complete marker and radiologic (brain and systemic) remission (20 months). Pt 2: 44 yo man, primary mediastinal non-seminomatous GCT. Prior tx: 2008, 4 x BEP + mediastinal mass resection; 2015, 4 x TIP; 2016, 1 x HDCE. In 2017, received 5 x GCG in SPIRE for a PET avid mediastinal/pulmonary relapse and AFP (alpha-fetoprotein) rise. Response: RECIST stable and &gt; 50% AFP reduction for 6 months (subsequent progression with intracerebral metastasis). Treatment was well tolerated. Grade 4 neutropenia/ thrombocytopenia occurred in both and febrile neutropenia in pt 1. Both required a 25% dose reduction in Cis/Gem. Conclusions: GCG produced exceptional clinical responses in both platinum refractory GCT pts. Prospective evaluation is warranted. Clinical trial information: 16332228.

Outcomes following surgery for primary mediastinal nonseminomatous germ cell tumors in the cisplatin era

ObjectiveTreatment of primary mediastinal nonseminomatous germ cell tumors involves cisplatin-based chemotherapy followed by surgery to remove residual disease. We undertook a study to determine short and long-term outcomes. MethodsA retrospective analysis of patients with primary mediastinal nonseminomatous germ cell tumors who underwent surgery at our institution from 1982 to 2017 was performed. ResultsA total of 255 patients (mean age, 29.2 years) were identified. Acute respiratory distress syndrome occurred postoperatively in 27 patients (10.9%), which was responsible for all 11 (4.3%) postoperative deaths. Of patients who developed acute respiratory distress syndrome, more patients received bleomycin-containing chemotherapy (25 out of 169; 14.8%) than non-bleomycin regimens (2 out of 77; 2.6%) (P = .004). With respect to variables independently predictive of long-term survival, evidence of choriocarcinoma before chemotherapy (n = 12) was determined to be an adverse factor (P = .006). In contrast, biopsy-proven elements of seminoma (n = 34) were predictive of improved survival (P = .04). The worst pathology identified in the residual mediastinal mass after chemotherapy was necrosis in 61 patients (25.0%), teratoma in 84 patients (34.4%), and malignant (persistent germ cell or non–germ cell cancer) in 97 patients (39.8%), which influenced overall survival (P < .001). Additionally, teratoma with stromal atypia (n = 18) demonstrated decreased survival compared with teratoma without atypia (n = 66; P = .031). Patients with malignancy involving >50% of the residual mass (n = 47) had a 2.3-fold increased risk of death compared with ≤50% malignancy (n = 45; P = .008). Finally, elevated postoperative serum tumor markers (n = 40) was significantly predictive of adverse survival (P < .001). ConclusionsIn the treatment of primary mediastinal nonseminomatous germ cell tumors, avoiding bleomycin-containing chemotherapy is important. Pre- and postchemotherapy pathology and postoperative serum tumor markers are independent predictors of long-term survival.

NAD(P)H: Quinone oxidoreductase (NQO1) and catalase expression in nonseminomatous germ cell tumors.

413 Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme which detoxifies quinones and reduces oxidative stress. NQO1 is expressed in multiple tumor types at levels up to 200-fold above normal tissue, including in breast, pancreatic, and non-small cell lung cancers. NQO1 bioactivatable drugs have the potential to deliver tumor-selective DNA damage and cell death by exploiting the elevation of NQO1. Alterations in catalase expression can cause marked cytoprotection. The ratio of NQO1:catalase activities is presumed to be a predictive marker for therapeutic activity of NQO1 bioactivatable drugs. There is no data available on NQO1 and catalase expression in germ cell tumors. Methods: Patients with germ cell tumor who underwent orchiectomy/tumor resection between January 2016 and December 2018 were identified from the Indiana University Melvin and Bren Simon Cancer Center database. Patients with non-seminomatous germ cell tumor of testis or primary mediastinal non-seminomatous germ cell tumor were selected. Immunohistochemistry staining for NQO1 and catalase was performed on tumor tissue. Results: NQO1 and catalase expression were assessed in 16 patients. Fifteen of 16 tumors stained positive for NQO1, 13 of which were moderately to strongly positive. Conversely, the majority of tumors were catalase deficient or only mildly positive for catalase. The details of the Immunostaining is summarized in the table below. Conclusions: Non-seminomatous germ cell tumors appear to have overexpression of NQO1 and deficiency of catalase. NQO1 bioactivatable agents could be beneficial in treating patients with refractory non-seminomatous germ cell tumors.[Table: see text]

Clinical features and outcomes of secondary somatic malignancy (SSM) associated with primary mediastinal nonseminomatous germ cell tumors (PM-NSGCT).

531 Background: The incidence of secondary somatic malignancy (SSM) arising from teratoma is increased in 2 settings; late relapse and primary mediastinal nonseminomatous germ cell tumors (PM-NSGCT). Here, we report the clinical features and outcomes of patients with SSM in the setting of PM-NSGCT. Methods: Between 1985 and 2018, 29 patients with PM-NSGCT and SSM who had sufficient clinical follow-up to evaluate outcome were identified. Clinical and pathologic parameters were reviewed. The Kaplan-Meier method was used to estimate overall survival (OS) from time of SSM diagnosis and the log rank test to compare estimates. Results: Median age was 28 years (range 18-59) and all patients were male. Most presented with local symptoms (n=24, 83%), elevated tumor markers (n=26, 90%), and disease isolated to the mediastinum (n=25, 86%). A total of 39 SSM histologies were present in the 29 cases, with 8 (28%) having 2 (n=6) or 3 (n=2) SSM histologies; 25 (86%) also had viable non-teratomatous GCT in the mediastinal mass. Sarcoma was found in all 29 cases including rhabdomyosarcoma (n=15), angiosarcoma (n=6), sarcoma NOS (n=5), spindle cell (n=4), PNET (n=3), and other (n=3). Non-sarcoma histologies (n=1 each) included AML, SCC, and neuroblastoma. Most patients received GCT-directed chemotherapy followed by an attempt at surgical resection (90%). With a median follow-up of 2 years for survivors, median OS was 1.8 years (95% CI 0-3.9 years), with 18 patients succumbing to disease. Complete surgical resection was achieved in 23 men (79%) and was associated with superior OS (3.1 vs. 0.3 years, p=0.005). At relapse or progression, 11 received SSM histology-directed and 7 GCT-directed chemotherapy with no difference in OS (1.3 vs. 1.2 years, p=0.993). 7 patients developed SSM in the form of leukemia, a finding associated with significantly inferior OS (0.3 vs. 3.0 years, p=0.009). Conclusions: Sarcoma is the predominant SSM histology associated with PM-NSGCT and portends a poor prognosis even with initially localized disease. Complete resection following chemotherapy is critical to achieving long-term survival whereas SSM in the form of leukemia portends especially poor outcome.

NON-SEMINOMATOUS GERM CELL TUMOR PRESENTING AS EARLY PERICARDIAL TAMPONADE

SESSION TITLE: Critical Care 3 SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: The most frequent mediastinal lesions in adults are thymoma, lymphoma, thyroid masses and germ cell tumors. Potential complications of these masses due to localized invasion include hemoptysis, post-obstructive pneumonia, and superior vena cava syndrome. However, our patient was found to have large pericardial effusion and signs of early cardiac tamponade, which as complications of extragonadal germ cell tumors, have rarely been previously reported. CASE PRESENTATION: A 28-year-old male presented with a 1-week history of pleuritic chest pain, worsening shortness of breath and non-productive cough. On physical examination, he was in distress and preferred sitting position. JVD was elevated and heart sounds were muffled. EKG showed sinus tachycardia with low voltage complexes. CXR showed contour deformity along the R border of the heart ( Image 1). CTA chest revealed a large pericardial effusion ( Image 2) with a heterogeneous anterior mediastinal mass which abut the pericardium ( Image 3) along with two nodules in the right lung parenchyma. Patient was admitted to the ICU where emergent echocardiogram showed findings suggestive of early tamponade. It was decided to drain the effusion percutaneously followed by right thoracoscopy along with wedge resection of the lung nodules and pericardial window. On labs, AFP came out be very high at 8132 (nl<11ng/ml), LDH 453 ( nl 199-220U/L) and b HCG 46( nl<4U/L). . Pericardial fluid cytology was negative for malignant cells. Tissue biopsy of the mass was done which showed Yolk sac tumor and wedge resection of lung nodule was positive for metastatic seedings; CT abdomen and pelvis showed no intraabdominal pelvic mass or lymphadenopathy. After sperm banking, patient was started on chemotherapy with cisplatin, etoposide, ifosfamide with MESNA. DISCUSSION: Extragonadal non-seminomatous germ cell tumors (NSGCTs) primarily affect men during the third and fourth decades of life and are more aggressive than their seminomatous counterpart. Majority of patients with mediastinal NSGCTs are symptomatic at the time of diagnosis, with chest pain, hemoptysis, cough, fever, or weight loss. Superior vena cava syndrome or pericardial tamponade is occasionally present. Mediastinal NSGCT presenting as early cardiac tamponade is rarely seen in clinical practice but its early recognition and treatment by emergent pericardiocentesis can be life-saving as was done in our patient. Tumor markers including APF, b-HCG, and LDH help in the diagnosis of these tumors but the definitive diagnosis and treatment is based on the results of the biopsy of the tumor. CONCLUSIONS: One of the major causes of anterior mediastinal masses, particularly in young adult males, is an extragonadal germ cell tumor. Pericardial tamponade as a result of such tumors is rare but should always be considered in the appropriate clinical context as early recognition and management can be lifesaving. Reference #1: Nichols CR. Mediastinal germ cell tumors. Clinical features andbiologic correlates. Chest 1991;99:472–9. Reference #2: Cohn W. Anterior mediastinal mass lesions. In: Basow D, ed. UpTo-Date. Waltham, MA: UpToDate; 2012. DISCLOSURES: No relevant relationships by Taha Ahmed, source=Web Response No relevant relationships by TALHA AHMED, source=Web Response No relevant relationships by Sidra Khalid, source=Web Response No relevant relationships by Safdar Khan, source=Web Response

Clinical Challenges in Diagnosis and Management of Acute Megakaryocytic Leukemia Associated with a Mediastinal Nonseminomatous Germ Cell Tumor

Clinical Challenges in Diagnosis and Management of Acute Megakaryocytic Leukemia Associated with a Mediastinal Nonseminomatous Germ Cell Tumor

MTE 23.02 Mediastinal Germ Cell Tumor

MTE 23.02 Mediastinal Germ Cell Tumor

Stereotactic radiation therapy for residual chemorefractory primary mediastinal non-seminomatous germ cell tumor after surgical thoracotomy

Stereotactic radiation therapy for residual chemorefractory primary mediastinal non-seminomatous germ cell tumor after surgical thoracotomy