Primary Mediastinal 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.

P53 Overexpression May Represent an Early Marker of Clinicopathologic Progression in Vasculogenic Mesenchymal Lesions of Germ Cell Tumor Origin.

Vasculogenic mesenchymal lesions (VMLs) of germ cell tumor origin are thought to originate in postpubertal-type yolk sac tumor componentsand include a spectrum of lesions from teratoma with vasculogenic stroma (TVS), to low and high-grade vasculogenic mesenchymal tumors (VMTs). VMLs exhibit rudimentary to well-developed neoplastic vessels within primitive mesenchyme, being considered a neoplastic reiteration of embryonic vasculogenesis in the splanchnic mesoderm of the yolk sac. They occur in patients with primary mediastinal germ cell tumors after chemotherapy, and a subset progresses to "somatic-type" sarcomas [including angiosarcoma (AS)], with high-grade VMTs likely portending a higher risk. Recently, we encountered a low-grade VMT that progressed to metastatic AS during follow-up. In this case, both the low-grade VMT and the subsequent AS demonstrated p53 overexpression, suggesting that p53 alterations may precede histopathologic transformation. To test this hypothesis, we evaluated neoplasms representing the entire spectrum of VMLs using p53 immunohistochemistry (IHC; clone DO-7, Dako). Overexpression was defined as nuclear positivity in > 80% of neoplastic cells. Because the distinction between high-grade VMT and AS can be subjective in some cases, they were grouped together in a single category. Thirty-nine VMLs were assessed: 16 high-grade VMT/AS, 19 low-grade VMT, and 4 TVS. Patient age ranged from 19 to 46 years (mean, 30 years; male = 97%). Four high-grade VMT/AS and one low-grade VMT showed p53 overexpression (5/39 VMLs, 13%; 4/16 high-grade VMT/AS, 25%). These tumors included 1 unequivocal AS and 1 high-grade VMT/AS with progression to rhabdomyosarcoma. The only low-grade VMT with p53 overexpression demonstrated progression to AS. Another high-grade VMT that progressed to sarcoma demonstrated p53 overexpression in the sarcoma component, but it was excluded because the VMT was not represented in the material availableat the time of the study. Lesions with intratumoral grade heterogeneity (classified based the highest grade), demonstrated more pronounced p53 overexpression in the high-grade components. P53 overexpression is associated with disease progression in a subset of VMTs and may precede morphologic transformation to sarcoma. Routine evaluation of VMTs with p53 IHC seems justified, with overexpressors likely requiring an close clinical surveillance.

Primary germ cell tumours of the mediastinum: A review with emphasis on diagnostic challenges.

This article will review current aspects of the histopathological, immunohistochemical and molecular analysis of primary mediastinal germ cell tumours (PMGCTs) as well as their aetiological, epidemiological, clinical and therapeutic features. PMGCTs represent an important differential diagnosis in the spectrum of mediastinal tumours, and their diagnosis is usually made on small tissue samples from core needle biopsies in combination with diagnostic imaging and serum tumour markers. As in lymphomas, a small biopsy is often the only viable tumour sample available from these patients, as they receive chemotherapy prior to eventual surgical resection. Pathologists therefore need to apply an efficient combination of immunohistochemical markers to confirm the diagnosis of a PMGCT and to exclude morphological mimics.

Second Hematologic Malignancies Associated With Primary Mediastinal Germ Cell Tumors: A Population-based Study.

Studies addressing second hematologic malignancies (SHMs) in patients with primary mediastinal germ cell tumors (PMGCTs) are scarce. To better describe this phenomenon, we analyzed a large case series from a population-based registry. The Surveillance, Epidemiology, and End Results database was used to report the clinical characteristics and incidence of SHMs in patients with PMGCT. Among 1297 PMGCTs, 27 cases (2.08%) of SHM were found, with a median latency period of 12 months (95% CI: 5-41). All SHM occurred in males, 20 of whom (74.1%) had a previous nonseminomatous tumor. Acute myeloid leukemia was the most frequent SHM, accounting for 13 cases, 4 of which were acute megakaryoblastic leukemia that occurred within 5 months of diagnosis. The median survival after the diagnosis of SHM was 6 months (95% CI: 2-41). The risk of SHM was significantly higher than expected for the reference population, with a standardized incidence ratio of 6.21 (95% CI: 3.31-10.62) and an absolute excess risk of 19.19 per 10,000 person-years. Patients with PMGCT are at a higher risk of developing SHMs than the general population, particularly acute myeloid leukemia. This risk ranges from synchronous diagnosis of acute megakaryoblastic leukemia to the later onset of other hematological disorders that might be related to PMGCT therapies. Our findings may help create follow-up schedules for patients with PMGCT and raise the level of suspicion surrounding this association.

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.

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)

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.

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.

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.

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.

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.

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.

Morphologic Changes in the Thymus Following Chemotherapy for Anterior Mediastinal Germ Cell Tumors: A Study of 91 Cases Emphasizing Pseudoneoplastic Features.

The interpretation of postchemotherapy resections of anterior mediastinal germ cell tumors plays a critical role in determining future patient management and prognosis. Treatment-related changes in the thymus may mimic residual teratoma or microcystic-pattern yolk sac tumor. There is limited extant information concerning therapy-related pseudoneoplastic thymic alterations. To provide diagnostic assistance to distinguish nonneoplastic thymic abnormalities secondary to chemotherapy from residual germ cell tumor. We retrospectively reviewed 91 resections of primary anterior mediastinal germ cell tumors with recognizable thymic gland following cisplatin-based chemotherapy. The cohort included 90 men and 1 woman (median age, 29 years). A spectrum of thymic epithelial alterations occurred, including cystic change (macrocysts [n = 21] or microcysts [n = 20]); hyperplasia with reactive atypia (n = 8); ciliated, mucinous, or columnar cell metaplasia (n = 3); and mature squamous metaplasia (n = 2). These changes were similar to so-called acquired multilocular thymic cysts, were often contiguous with and adjacent to normal thymic epithelium, and lacked the neoplastic-type atypia seen in teratomatous elements in this setting. In 1 case, confluent microcysts closely mimicked the appearance of yolk sac tumor but lacked other distinctive features of that neoplasm and its characteristic immunoreactivity. Recognition of therapy-induced thymic changes is important to avoid misinterpretation as residual teratoma or yolk sac tumor. Continuity with and proximity to benign thymic epithelium, absence of neoplastic-type atypia, and awareness of this phenomenon are important in avoiding this pitfall.

Establishment and validation of an individualized nomogram for survival prediction of primary mediastinal germ cell tumors based on the SEER database.

BackgroundPrimary mediastinal germ cell tumors (PMGCT) represent a rare but sometimes highly aggressive type of mediastinal tumors. The current prognostic models for PMGCT are insufficient. This study was undertaken to establish and validate an individualized nomogram for predicting the overall survival (OS) of patients with PMGCT.MethodsWe conducted a retrospective analysis of patients with PMGCT diagnosed between 2000 and 2018 in the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Clinical variables included surgery subtype, gender, treatment regimens, age, histology, tumor size, stage, chemotherapy, radiation, race, and survival-related information. The main outcome measure was survival duration. The Kaplan-Meier method along with the log-rank test were utilized to estimate the OS. Independent prognostic factors were identified by performing the univariate and multivariate Cox proportional hazards regression analyses, from which an individualized nomogram was constructed to predict 3-, 5-, and 10-year OS of patients with PMGCT. The concordance index (C-index) and calibration curve were used to verify the discrimination and accuracy of the nomogram.ResultsA total of 845 patients with PMGCT were recruited from the SEER database and further randomly assigned to a training set (n=635) and a validation set (n=210) at a ratio of 7:3. The 3-, 5-, and 10-year OS for overall PMGCT was 70.0%, 67.1%, and 63.9%, respectively. Cox regression analysis indicated that age, tumor size, stage, chemotherapy, radiation, histology, and surgery type were as independent factors for OS in patients with PMGCT (P<0.05). An individualized nomogram for OS was constructed utilizing these variables, with the C-index of 0.714 [95% confidence interval (CI): 0.695 to 0.743] and 0.756 (95% CI: 0.735 to 0.787) in the training and validation groups. Moreover, good levels of agreement were observed according to the calibration curve between the predicted and actual 3-, 5-, and 10-year survival rates both in the training and validated cohorts, showing that the model could accurately predict patient prognosis.ConclusionsThis study documented the first attempt at establishing and validating a novel nomogram for predicting the 3-, 5-, and 10-year OS probabilities of PMGCT. The prognostic nomogram was demonstrated to have good performance for predicting individualized OS of patients with PMGCT.