Clinical Features and Therapeutic Outcomes Comparing Primary Mediastinal Large B-cell Lymphoma to Mediastinal Hodgkin Disease.

Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Isolated central nervous system relapse in two adolescents with primary mediastinal large B-cell lymphoma after treatment with R-DA-EPOCH.

The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.

The Other Side of the Curtain.

In this narrative medicine essay, a newly minted pediatric critical care physician learns firsthand what holistic medical care is from the love and attention she received during a hospitalization for mediastinal lymphoma.

[Chinese expert consensus on the diagnosis and management of primary mediastinal large B-cell lymphoma (2024)].

Primary mediastinal large B-cell lymphoma (PMBL) is an aggressive B-cell lymphoma that is thought to arise from thymic (medullary) B cells and has unique clinicopathologic and molecular features. In recent years, the understanding of the pathogenesis and treatment of PMBL has been updated to varying degrees, particularly in the area of new drug therapy. In order to improve the diagnosis and treatment of PMBL in China, the Lymphocyte Disease Group of the Chinese Medical Association (CMA) and the Anti-Lymphoma Alliance of the Chinese Society of Clinical Oncology (CSCO) commissioned a group of experts to formulate this consensus.

Survival difference among adult and pediatric mediastinal yolk sac tumors cases: A meta-analysis of case reports.

BACKGROUND: Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST. METHODS: Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586). RESULTS: Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS. CONCLUSION: Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.

Updates in the Management of Primary Mediastinal B Cell Lymphoma.

Primary mediastinal B cell lymphoma (PMBCL) is considered a distinct pathology according to the WHO classification of lymphoid malignancies. Patients have a better prognosis after the addition of Rituximab to anthracycline-based chemotherapy. The role of consolidative radiotherapy is controversial after the approval of dose-adjusted R-EPOCH and the selection of patients to undergo radiotherapy is based on end-of-therapy PET CT. In the relapsed/refractory setting, new approved drugs and other under investigation have improved patient outcomes. This review summarizes the different treatment modalities in (PMBCL) in the frontline and the relapsed/refractory settings.

Child Neurology: Anti-Hu Encephalitis in an Adolescent With a Mediastinal Seminoma.

Anti-Hu antibodies are associated with autoimmune syndromes, mainly limbic encephalitis, encephalomyelitis, and painful sensory polyneuropathy (Denny-Brown). We report the case of a 15-year-old boy presenting with epilepsia partialis continua (EPC) found to have a right middle frontal gyrus brain lesion without atrophy or contralateral involvement. After partial resection, neuropathology revealed neuronal loss, reactive gliosis and astrocytosis, and perivascular mononuclear inflammatory infiltrate and features of neuronophagia resembling Rasmussen encephalitis. Suboptimal response to antiseizure drugs and surgery prompted further workup with identification of positive serum anti-Hu antibodies and a mediastinal seminoma. The patient was treated with immunotherapy including steroids, IV immunoglobulin, azathioprine, rituximab, plasmapheresis, and mediastinal lesion resection. However, he continued to experience EPC and psychomotor impairment along with left hemiparesis and dysarthria. Given clinical progression with failure to respond to immunotherapy and antiseizure polytherapy, hemispherotomy was attempted and seizure freedom achieved. A review of the literature found only 16 cases of neurologic presentations associated with anti-Hu antibodies in children, confirming the rarity of EPC in these cases. Thus, this report provides a new observation of germ cell mediastinal tumor associated with anti-Hu antibodies in children, broadening the spectrum of anti-Hu-associated neurologic disorders in children and highlighting the importance of considering antineuronal antibody testing in children presenting with EPC and brain lesions suggestive of Rasmussen encephalitis.

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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: A nomogram based on staging and blood routine examination results was established to accurately and consistently predict the prognosis of patients with nonseminomatous PMGCTs.

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

INTRODUCTION: The purpose of this study was to perform a population-based investigation to assess the disease characteristics and prognosis of children and adolescents with malignant mediastinal germ cell tumors (MMGCT). METHODS: Data on the demographics, treatment, and survival outcomes of children and adolescents with MMGCT from January 1, 2000 to December 31, 2018 were obtained. To compare survival curves, the log-rank test was employed. The generation of survival curves based on different parameters was done using Kaplan-Meier estimations. Cox proportional hazards regression was performed to determine the variables linked to disease-specific survival. RESULTS: The selection criteria were met by 152 MMGCT patients, 130 of whom were male. Fifty three cases of mixed germ cell tumors (GCTs), 41 cases of malignant teratomas, 26 cases of yolk sac tumors, 14 cases of seminoma, 13 cases of choriocarcinomas, and five cases of embryonal carcinoma were reported. Overall survival at 3 and 5 y for all patients was 63.1% and 61.2%, respectively. Malignant teratoma, yolk sac tumors, and mixed GCTs in children and adolescents had comparable survival rates, while those with choriocarcinoma and embryonal carcinoma showed the worst prognosis. Embryonal carcinoma, malignant teratoma, mixed GCTs, and choriocarcinoma were found as risk factors by multivariate Cox proportional hazards analysis. In contrast, surgery and younger age were protective factors. However, chemotherapy alone showed no survival benefits. CONCLUSIONS: Our population-based evidence showed that MMGCT had worse prognosis in older children and adolescents. Choriocarcinomas and embryonal carcinomas had the worst prognosis. Surgery can prolong survival time. Chemotherapy and radiotherapy were not associated with improved prognosis.

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

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

A review on pulmonary and mediastinal synovial sarcoma.

Sarcoma is defined as a tumor located in the thoracic cavity. However, sarcoma can occur on every side of the body. Synovial sarcoma is a rare soft tissue tumor originating from pluripotent with a high malignancy rate. The most common predilection of synovial sarcoma is in the joints. Primary synovial sarcoma of the lung and mediastinum are rare tumors and generally malignant. There are only a few cases have been reported. Definite diagnosis is made by histopathological, immunohistochemistry, and cytogenetic examination. The management strategy for synovial sarcoma requires multimodality treatment with surgery, chemotherapy, and radiotherapy. However, effective and relatively non-toxic therapy for primary synovial sarcoma is still developed. The five years life expectancy is higher if the patient received adjuvant radiotherapy and/or chemotherapy after surgery.

Targeted Mutational Profiling Reveals Clonal Relationships in Metachronous Occurrence of Classic Hodgkin and Mediastinal Large B-Cell Lymphomas.

Classic Hodgkin lymphoma (CHL) patients may infrequently present with a prior or recurrent disease with discordant histology resembling non-Hodgkin lymphomas. These include primary mediastinal large B-cell lymphoma (PMBL), diffuse large B-cell lymphoma (DLBCL), or mediastinal gray-zone lymphoma (MGZL). Such patients are often refractory to standard therapy and their diagnosis is hampered by significant morphologic and immunophenotypic overlap and insufficient molecular data. Among 509 CHL patients seen at an academic medical center, 6 patients had a prior or subsequent diagnosis different from CHL. Paired tissue samples were evaluated by targeted mutational analysis using a 164-gene panel. Our findings show multiple shared variants indicative of a clonal relationship between the CHL and the PMBL, DLBCL, or MGZL diagnoses. Most frequent mutated genes included TNFAIP3 (4 of 6, 66.7%), STAT6 (3 or 6, 50%), ARID1A (3 of 6, 50%), and XPO1 (3 of 5, 60%). Three patients showed the same oncogenic variant within the XPO1 gene (E571K), and mutations in TNFAIP3 and B2M were observed in 2 of the 5 patients with shared variants. In addition, differences in the mutation profile between the lymphoma pairs were also observed, which could represent clonal evolution. Mutational profiling could be of benefit in patients with recurrent/refractory disease with discordant histology, where the clonal relationship could be helpful to inform and guide therapeutic decisions. These findings provide further evidence of a true biological continuum surrounding CHL, PMBL, DLBCL, and MGZL and shed light on underlying genetic events and their clinical impact.

Timely diagnostics and safe procedures in children with anterior mediastinal masses (AMMs): a qualitative review of the AMM protocol at BC Children's Hospital in Vancouver BC.

The presence of an anterior mediastinal mass should prompt rapid triage, workup and treatment to effectively manage and prevent emergent complications. Implementation of an AMM protocol can ensure the response is standardized and coordinated. Importantly, such a protocol can encourage prompt multi-disciplinary communication to mitigate risks associated with procedures required for timely diagnosis. The aim of this review is to evaluate the BC Children's Hospital's Pediatric New/Suspected Anterior Mediastinal Mass (AMM) Protocol. Retrospective chart review was conducted for 18 patients admitted from February 2016 to May 2020 with AMM for whom the protocol was enacted. Primary parameters assessed presence of high-risk feature at time of presentation, time from admission and/or protocol activation to specific time points, including imaging, first diagnostic procedure, and diagnosis. Data regarding perioperative management, including anesthetic considerations and peri-operative complications, was also collected. Mean time from protocol activation to first diagnostic procedure and diagnosis were 1.88 days (range 0-7) and 2.24 days (range 0-7), respectively. The majority of procedures were conducted under sedation (n = 77, 64%), followed by general anesthetic (GA; n = 34, 28%) and local anesthetic (n = 10, 8%). Despite 15 cases having more than one high risk feature, pre-operative steroids were only administered for four of the total 158 procedures (3%) and extracorporeal life support (ECLS) and otolaryngology (ENT) were only required for immediate availability for seven procedures (4%). Furthermore, only 10 procedures (8%) had associated complications and none of these complications resulted in patient death. Our data demonstrate that implementation of a streamlined multi-disciplinary protocol can expedite time to diagnosis without impacting patient safety.

Extragonadal Germ Cell Tumors of the Mediastinum and Retroperitoneum: A Surveillance, Epidemiology, and End Results-based Study.

OBJECTIVES: Extragonadal germ cell tumors (EGCT) are a rare entity, most of them being located in the mediastinum and retroperitoneum. Information on these tumors is scarce, requiring carrying out large population-based studies to better understand these diseases. We aimed to determine the clinical features and prognosis of patients with EGCT of the mediastinum and retroperitoneum. MATERIALS AND METHODS: Demographic and clinicopathological features of patients diagnosed with EGCT of the mediastinum and retroperitoneum from 1975 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 1674 patients were included, 1297 (77.5%) of mediastinal origin and 377 (22.5%) of retroperitoneum. Nonseminomatous tumors (56.3%) were slightly more frequent than seminomas (43.7%) with similar distribution between mediastinum and retroperitoneum. After a median follow-up of 137 months, the median overall survival was 263 months (95% CI, 220-296) whereas the median cause-specific survival (CSS) has still not been reached. The 10-year overall survival and CSS were 57.4% (95% CI, 55-59.7) and 63% (95% CI, 60.6-65.2) respectively. Multivariate analysis showed that older age, mediastinal location, nonseminomatous histology, and distant disease at diagnosis were independent prognostic factors correlated with a worse prognosis. Patients with mediastinal choriocarcinoma and embryonal carcinoma have the worst prognosis, both with a median CSS of only 12 months. CONCLUSIONS: Despite a decreasing incidence observed in recent decades, EGCT continues to represent a challenge for oncologists. The prognosis of choriocarcinoma and embryonal carcinoma of the mediastinum remains poor and treatment strategies need to be improved urgently.

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

BACKGROUND: 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. METHODS: The authors retrospectively reviewed children 0-18 years 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. RESULTS: 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 that surgical management was the only independent predictor for superior OS. CONCLUSIONS: 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.