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

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

Both serum and tissue Galectin-1 levels are associated with adverse clinical features in neuroblastoma.

BACKGROUND: Neuroblastoma is one of the most common pediatric solid tumors. Although the 5-year overall survival rate has increased over the past few decades, high-risk patients still have a poor prognosis due to a lack of biomonitoring therapy. This study was performed to investigate the role of Galectin-1 in neuroblastoma biomonitoring therapy. PROCEDURE: A tissue microarray containing 37 neuroblastoma tissue samples was used to evaluate the correlation between Galectin-1 expression and clinical features. Blood samples were examined to better understand whether serum Galectin-1 (sGalectin-1) could be used for biomonitoring therapy. Kaplan-Meier analysis and ROC analysis was conducted to distinguish the outcome associated with high or low expression of Galectin-1 in patients with neuroblastoma. RESULTS: Increased Galectin-1 expression was found in neuroblastoma and it was further demonstrated that elevated tissue Galectin-1 expression was related to INSS stage, histology, bone marrow metastasis, and poor survival. sGalectin-1 levels were higher in newly diagnosed patients with neuroblastoma than healthy subjects. Patients with elevated sGalectin-1 through treatment cycles correlated with the poor chemo-responses and tended to have worse outcomes, such as metastasis or stable tumor size, whereas gradually decreasing sGalectin-1 levels correlated with no observed progression in clinical symptoms. CONCLUSIONS: Tissue and serum Galectin-1 levels were associated with adverse clinical features in patients with neuroblastoma, and sGalectin-1 could be a potential biomarker for monitoring therapy.

Mistaken Identity: Asthma and Croup in a Previously Healthy 9-Year-Old Male.

Cough is one of the most common presenting complaints encountered in primary care settings and the emergency department. In 2010, the Centers for Disease Control and Prevention reported approximately 31 million visits to ambulatory care centers for cough, making cough the most frequent presenting complaint in ambulatory visits (2010 National Ambulatory Medical Care Survey). Significant causes of cough can often be overlooked because it is a common symptom of a myriad of pathologies. We report the case of an otherwise healthy 9-year-old male who presented with worsening cough over a month and a half, subsequently noted to have a mediastinal mass, and diagnosed with lymphoma. We discuss the challenges of diagnosing life-threatening pathologies, which present with common symptoms.

[Primary mediastinal choriocarcinoma: A case report and literature review].

Primary mediastinal choriocarcinoma in male is not a very common disease, with nonspecific clinical manifestations. Gynecomastia and testicular atrophy are present in some cases. The levels of serum human chorionic gonadotropin are often significantly increased. Giant lump in the mediastinum and bilateral lungs multiple metastases can be seen on the computed tomography for lung. The diagnosis for it depends on pathological biopsy. Current treatment method is a comprehensive, consisting of chemotherapy, radiotherapy and surgery. This paper reported a case of primary mediastinal choriocarcinoma in male, who were diagnosed and treated in the Second Xiangya Hospital of Central South University. He was admitted for cough and hemoptysis, and finally diagnosed by biopsy. The prognosis is very poor. Therefore, it is important to take physical examination regularly because it can be detected and diagnosed early.

[Mediastinal large B-cell lymphoma].

The group of mediastinal B-cell lymphomas from large cells includes such pathogenic-connected diseases as diffuse large-cell B-cell lymphoma, primary mediastinal large-cell B-cell lymphoma, and recently separated rare nosological form--mediastinal lymphoma of grey zone and classical Hodgkin's lymphoma. Comparative characteristics of these tumors allow revealing many similarities, which in some cases creates significant difficulties for differential diagnosis. Wherein the members of the group differ by their clinical and epidemiological features, prognosis and require different treatment.

Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial.

BACKGROUND: Poor prognosis germ-cell tumours are only cured in about half of patients. We aimed to assess whether treatment intensification based on an early tumour marker decline will improve progression-free survival for patients with germ-cell tumours. METHODS: In this phase 3, multicentre, randomised trial, patients were enrolled from France (20 centres), USA (one centre), and Slovakia (one centre). Patients were eligible if they were older than 16 years, had evidence of testicular, retroperitoneal, or mediastinal non-seminomatous germ cell tumours based on histological findings or clinical evidence and highly elevated serum human chorionic gonadotropin or alfa-fetoprotein concentrations that matched International Germ Cell Cancer Consensus Group poor prognosis criteria. After one cycle of BEP (intravenous cisplatin [20 mg/m(2) per day for 5 days], etoposide [100 mg/m(2) per day for 5 days], and intramuscular or intravenous bleomycin [30 mg per day on days 1, 8, and 15]), patients' human chorionic gonadotropin and alfa-fetoprotein concentrations were measured at day 18-21. Patients with a favourable decline in human chorionic gonadotropin and alfa-fetoprotein continued BEP (Fav-BEP group) for 3 additonal cycles, whereas patients with an unfavourable decline were randomly assigned (1:1) to receive either BEP (Unfav-BEP group) or a dose-dense regimen (Unfav-dose-dense group), consisting of intravenous paclitaxel (175 mg/m(2) over 3 h on day 1) before BEP plus intravenous oxaliplatin (130 mg/m(2) over 3 h on day 10; two cycles), followed by intravenous cisplatin (100 mg/m(2) over 2 h on day 1), intravenous ifosfamide (2 g/m(2) over 3 h on days 10, 12, and 14), plus mesna (500 mg/m(2) at 0, 3, 7 and 11 h), and bleomycin (25 units per day, by continuous infusion for 5 days on days 10-14; two cycles), with granulocyte-colony stimulating factor (lenograstim) support. Centrally blocked computer-generated randomisation stratified by centre was used. The primary endpoint was progression-free survival and the efficacy analysis was done in the intention-to-treat population. The planned trial accrual was completed in May, 2012, and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00104676. FINDINGS: Between Nov 28, 2003, and May 16, 2012, 263 patients were enrolled and 254 were available for tumour marker assessment. Of these 51 (20%) had a favourable marker assessment, and 203 (80%) had an unfavourable tumour marker decline; 105 were randomly assigned to the Unfav-dose-dense group and 98 to the Unfav-BEP group. 3-year progression-free survival was 59% (95% CI 49-68) in the Unfav-dose-dense group versus 48% (38-59) in the Unfav-BEP group (HR 0·66, 95% CI 0·44-1·00, p=0·05). 3-year progression-free survival was 70% (95% CI 57-81) in the Fav-BEP group (HR 0·66, 95% CI 0·49-0·88, p=0·01 for progression-free survival compared with the Unfav-BEP group). More grade 3-4 neurotoxic events (seven [7%] vs one [1%]) and haematotoxic events occurred in the Unfav-dose-dense group compared with in the Unfav-BEP group; there was no difference in grade 1-2 febrile neutropenia (18 [17%] vs 18 [18%]) or toxic deaths (one [1%] in both groups). Salvage high-dose chemotherapy plus a stem-cell transplant was required in six (6%) patients in the Unfav-dose-dense group and 16 (16%) in the Unfav-BEP group. INTERPRETATION: Personalised treatment with chemotherapy intensification reduces the risk of progression or death in patients with poor prognosis germ-cell tumours and an unfavourable tumour marker decline. FUNDING: Institut National du Cancer (Programme Hospitalier de Recherche Clinique).

Outcome following resection for patients with primary mediastinal nonseminomatous germ-cell tumors and rising serum tumor markers post-chemotherapy.

BACKGROUND: To assess the outcome of surgical resection in patients with primary mediastinal nonseminomatous germ-cell tumors (PMNSGCT) with rising serum tumor markers (STM) following standard platinum-based chemotherapy. PATIENTS AND METHODS: A total of 158 consecutive patients with PMNSGCT who received platinum-based chemotherapy followed by complete surgical extirpation of residual disease at Indiana University from 1982 to 2007 were retrospectively reviewed. Thirty-five of these 158 patients had rising STM at time of resection. RESULTS: Thirty-five patients (34 males and 1 female) comprise the basis of this report. Three patients had rising human chorionic gonadotropin, and the remaining 32 patients had rising alpha-fetoprotein at the time of thoracic surgery. Twenty-four of the 35 (69%) pathologically demonstrated viable germ-cell tumor, while 8 patients had teratoma and 3 patients had necrosis only at time of resection, despite the presence of rising STM. Twenty-seven patients normalized their tumor markers postoperatively. Twenty-one of 35 died, 5 were lost to follow-up, and 9 are alive. Of the nine patients alive, seven are continuously disease free with median follow-up of 64 months (range 25-220 months). CONCLUSION: The presence of rising STM doesn't preclude successful therapy with surgical resection, especially if carried out by experienced thoracic surgical oncologists.

Mediastinal teratoma mimicking massive pleural effusion.

Immature mediastinal teratoma is very rare, found in only 1% of all mediastinal teratomas. Raised serum alpha feto-protein acts as important surrogate marker for both diagnosis and follow up in such cases. Surgery and adjuvant chemotherapy are keys in the management, especially in patients older than 15 years of age. We present a 14-year-boy presenting clinico-radiologically as left sided massive pleural effusion. Raised serum marker as well as excision biopsy of the mediastinal mass following thoracotomy were indicative of a diagnosis of immature teratoma.

Camrelizumab Plus Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin in Relapsed/Refractory Primary Mediastinal B-Cell Lymphoma: A Single-Arm, Open-Label, Phase II Trial.

PURPOSE: Patients with relapsed/refractory primary mediastinal B-cell lymphoma (rrPMBCL) represent a particularly challenging population to treat, with few life-saving treatment options in the context of a dismal prognosis. PATIENTS AND METHODS: In this open-label, single-arm, phase II study, the safety and efficacy of combined regimen of chemotherapy consisting of gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) plus anti-PD-1 antibody camrelizumab was assessed in rrPMBCL. Patients received chemo-immunotherapy every 3 weeks until the second confirmed complete response (CR) or up to 12 cycles, followed by camrelizumab monotherapy for up to 1 year. The primary endpoints were objective response rate (ORR) and safety. RESULTS: Twenty-seven response evaluable patients were enrolled, who received a median of three first-line therapies, 59% with bulky disease. The ORR was 74%, including 56% with a CR. A median time of 1.7 months to response was observed, with 78% exhibiting tumor shrinkage at the first evaluation. After 24.8 months median follow-up, the median duration of response was not reached, with a 65% 2-year estimated response rate. Thirteen responders remained in sustained complete remission. Estimated 24-month progression-free survival and overall survival rates were 48.2% and 81.5%, respectively. Any grade and grade 3 treatment-related adverse events (AE) occurred in 93% and 33% of patients, respectively; with no grade 4 or 5 AEs. Baseline levels of IL10, IFNγ, and soluble Fas were associated with objective response. CONCLUSIONS: Camrelizumab plus GVD chemotherapy offers a potent option as life-saving chemo-immunotherapy with promising efficacy and a manageable safety profile for patients with rrPMBCL, especially with bulky aggressive disease.

Molecular and phenotypic characterization of an early T-cell precursor acute lymphoblastic lymphoma harboring PICALM-MLLT10 fusion with aberrant expression of B-cell antigens.

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is usually diagnosed based on the presence of immature lymphoid marker terminal deoxynucleotidyl transferase (TdT), and T-cell specific markers, specifically CD3, by immunohistochemistry (IHC) staining on bone marrow and/or extramedullary tissue. We present a novel, TdT and CD3 negative, aggressive early T-cell precursor LBL (ETP-LBL) initially misdiagnosed as a high grade B-cell lymphoma due to expression of CD79a and the erroneous detection of BCL2/IGH fusion. The patient was eventually evaluated using molecular diagnostic techniques, including fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) assays that demonstrated PICALM-MLLT10 fusion and a NOTCH1 mutation in the absence of BCL2/IGH fusion. The use of NGS, specifically mate-pair sequencing (MPseq), subsequently confirmed an in-frame PICALM-MLLT10 fusion. Our retrospective analysis showed that PICALM-MLLT10 fusion has no association with CD3/TdT negativity, as 6/49 T-ALL/LBL cases from Mayo Clinic database (01/1998-09/2018), including this case, were noted to have PICALM-MLLT10 fusion; however, none of the other cases were associated with CD3/TdT negativity. We emphasize the importance of a comprehensive hematopathologic evaluation including multiple molecular studies for the appropriate interrogation and classification of a difficult acute leukemia diagnosis, and to prevent potential diagnostic errors of clinical significance.

Metachronous mediastinal seminoma occurring after intracranial germinoma in an adolescent.

We report a case of a mediastinal seminoma occurring 19 months after the resolution of a pineal germinoma. A 15-year-old boy with headaches and visual changes was diagnosed with a pineal germinoma by biopsy and mildly elevated beta-human chorionic gonadatropin (beta-HCG) in serum and cerebral spinal fluid. Radiation therapy leads to the resolution of his pineal germinoma and normalization of the beta-HCG. A mediastinal seminoma (germinoma) was diagnosed nearly 2 years later because of rising serum beta-HCG. There was no evidence of recurrent central nervous system disease. The patient underwent systemic chemotherapy with the complete resolution of the mediastinal seminoma.

Extracorporeal membrane oxygenation (ECMO) assisted mediastinal tumor resection and superior vena cava replacement are safe and feasible.

BACKGROUND: How to maximally improve the drainage of intracranial and upper body venous and to reduce neurological complications during thoracic tumor-causedsuperior vena cava replacement are still clinical problems to be solved. METHODS: We have innovatively used the bilateral jugular vein-left femoral vein ECMO shunting to perform mediastinal tumor resection and superior vena cava replacement in a 50-year-old woman. RESULTS: During the operation, this technique maintained the patient's hemodynamic stability, improved the cerebral oxygen saturation and reduced the cerebral ischemia, hypoxia as well as the neurological complications. CONCLUSION: It is indicated for patients with superior vena cava replacement who are unable to perform venous bypass (such as innominate vein to right atrial bypass) or venous shunting (such as differential pressure drainage from internal jugular vein to femoral vein).

Growing teratoma syndrome in primary mediastinal germ cell tumor: our experience.

BACKGROUND: Growing teratoma syndrome is a rare phenomenon seen in nonseminomatous germ cell tumors after chemotherapy, where the tumor grows paradoxically despite normalization of tumor markers. It has been found in various locations, most commonly, the retroperitoneum in association with metastatic disease. The occurrence of growing teratoma syndrome in a mediastinal primary is very rare and there are only a few reports in the literature. METHODS: In a retrospective review, out of 12 patients with mediastinal involvement by a germ cell tumor, 5 had a primary from the mediastinum. We present a series of 3 cases of primary germ cell tumor of the mediastinum, which after chemotherapy, fulfilled the criteria for growing teratoma syndrome and were managed with surgical excision. CONCLUSION: Development of growing teratoma syndrome in a primary mediastinal germ cell tumor is extremely rare. Its awareness and early detection can lead to successful surgical excision and long-term cure.

Serum cytokine in response to chemo-radiotherapy for Hodgkin's disease.

AIMS AND BACKGROUND: Mediastinal radiotherapy and multiple-drug chemotherapy, including bleomycin employed in the treatment of Hodgkin's disease, can produce lung toxicity leading to fibrosis. There is increasing evidence of the involvement in the fibrosing process of different cytokines and growth factors such as TNF-alfa, IL-1 beta, TGF-beta and PDGF. MATERIAL AND METHODS: In a pilot study, we evaluated lung function in 20 patients suffering from Hodgkin's disease, mainly in stage II A, submitted to multiple-drug chemotherapy including bleomycin (ABVD) and mediastinal radiotherapy and correlated its modifications with serum concentration of the cytokines determined by immunoenzymatic assay. Spirometry and transfer lung function for carbon monoxide (DLCO) were performed before, at the end of chemotherapy, at the end of radiotherapy and after a follow-up of 6 and 12 months. RESULTS: DLCO decreased at the end of the combined treatment and then remained constantly decreased. TNF-alfa, TGF-beta and PDGF-alfa concentrations did not change, whereas IL-1 beta significantly increased after the completion of the combined treatment and after a follow-up of 6-months and then declined to normal values after 12 months. The serum concentration of the cytokine was significantly higher in patients who had a DLCO < 75% of predicted after 1 year than in patients with a DLCO > 75%. CONCLUSIONS: The results indicate a potential role of IL-1 beta in the pathogenesis of chemoradiotherapy-induced lung toxicity, which needs to be confirmed in a larger patient population.

Outpatient video-assisted thoracoscopic surgery (VATS) for ectopic mediastinal parathyroid adenoma: a case report and review of the literature.

Up to 20% of abnormal parathyroid glands causing primary or secondary hyperparathyroidism are located ectopically. Of these, approximately 1%-2% reside in the mediastinum and may not always be resectable through a traditional cervical approach. Recently, video-assisted thoracoscopic surgery (VATS) has arisen as a minimally invasive method for resecting mediastinal parathyroid glands and avoiding the complications and higher morbidity of a sternotomy. In this paper, we present a case of a patient with asymptomatic hyperparathyroidism and an ectopic parathyroid on sestamibi imaging in the mediastinum. Initially, the patient underwent a bilateral cervical exploration, left upper parathyroidectomy, and partial thymectomy; however, postoperatively, he continued to have persistently elevated serum calcium and parathyroid hormone levels. Ultimately, management consisted of parathyroidectomy through a VATS approach, along with intraoperative parathyroid assay monitoring and frozen-section pathologic analysis. The patient was successfully discharged to home several hours after surgery. To our knowledge, this is the first reported case of mediastinal ectopic parathyroid adenoma treated with outpatient VATS.

[A case of mediastinal cancer of unknown primary with elevation of serum concentrations of interleukin-6].

Interleukin-6(IL-6)is an inflammatory cytokine. It's produced by monocyte, lymphocyte, vascular endothelial cell, and fibroblast. Elevation of serum concentrations of IL-6 is reported a lot of kind of diseases, such as cancer, infection, inflammatory diseases. But it is production mechanism was still unknown. A 67-year-old man was referred to our hospital because of treatment against the large mediastinal cancer of unknown primary. He had complication with superior vena cave syndrome. After he was exposed to irradiation, the tumor size was reduced, his symptoms were improved and the serum IL-6 level was decreased.

Tumor induced hypercalcemia in a patient with mediastinal synovial sarcoma.

Tumor-induced hypercalcemia is a frequent complication of advanced cancers, but it has been rarely reported in patients with sarcoma. We report a 16 year-old boy presenting with polyuria, polydipsia and severe dehydration. Laboratory examination revealed severe hypercalcemia (serum calcium 23 mg/dl) which caused emaciation and was accompanied by low serum phosphorus and suppressed parathyroid hormone. Diagnostic imaging revealed a huge anterior mediastinal mass. Hypercalcemia was successfully treated with pamidronate, a bisphosphonate, and the patient underwent surgical resection. Pathological and immunohistochemical analyses confirmed a diagnosis of biphasic synovial sarcoma. To our knowledge, this is the first case of mediastinal synovial sarcoma presenting with hypercalcemia.

Primary mediastinal large B-cell lymphoma: a single-center study of clinicopathologic characteristics.

Primary mediastinal large B-cell lymphoma (PMLBCL) is a subset of LBCL with unique clinicopathologic features. Some studies have raised the question of differences in biological features and clinical course among patients from different parts of the world. We conducted a retrospective clinicopathologic analysis of 24 patients with PMLBCL from a single center in Croatia. We also conducted the first investigation of the frequency of lymphotropic viruses human herpesvirus 6 (HHV-6) and HHV-8 in lymphoid lesions of this disease. The clinical characteristics of the patients were as expected, with high International Prognostic Index scores, elevated serum lactate dehydrogenase (LDH) levels, and bulky disease being adverse prognostic factors. Only 6 patients (25%) showed CD30 expression, and Bcl-6 protein expression was, in our series, prognostically favorable (P = .0401). One patient's tumor had detectable HHV-6 genome sequence, but no HHV-8 sequences were detected in any tumors. Two thirds of the patients received CHOP chemotherapy (cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone) with a relatively low complete remission rate (43.8%; median follow-up, 33.8 months). This study confirmed the moderate preponderance among PMLBCL patients of young females with B symptoms and elevated LDH levels. The CHOP regimen proved effective as first-line therapy only in patients with limited disease. Therefore, other third-generation chemotherapy protocols may be considered for treatment, especially in patients with bulky and advanced disease.

Stable hematopoietic recovery after peripheral blood stem cell transplantation in patients receiving high-dose chemotherapy for advanced germ cell tumors.

AIM: The objective of this study was to evaluate the utility of CD34-positive peripheral blood stem cell transplantation (PBSCT) in the hematopoietic recovery, in patients receiving high-dose chemotherapy (HDCT), for advanced germ cell tumor (GCT). MATERIALS AND METHODS: This study included 41 patients with advanced GCT, who were treated with HTCT combined with PBSCT. PBSCs were harvested after conditioning chemotherapy followed by the administration of granulocyte colony-stimulating factor. A retrospective analysis of a total of 86 PBSCTs was carried out focusing on the effects of several factors, including age (<35 years versus > or = 35 years), CD34-positive cell dose (<5.0 x10(6)/kg versus > or =5.0 x10(6)/kg), indication of HDCT (first-line versus salvage) and previous history of HDCT before PBSCT (with versus without), on hematopoietic recovery after PBSCT. RESULTS: The median number of CD34-positive PBSCs collected during a single apheresis and the median cumulative number of CD34-positive PBSCs from each patient were 8.3x10(6)/kg and 23.2x10(6)/kg, respectively. The median number of PBSCT performed in each patient was two and the median number of CD34-positive cells transplanted during a single course was 5.7x10(6)/kg. The median recovery times to white blood cells (WBC) greater than 500/microl, 1000/microl and 2000/microl were 8, 9 and 10 days, respectively, following PBSCT, while that to neutrophils greater than 500/microl and that to platelets greater than 50000/microl were 9 and 13 days, respectively, following PBSCT Only the recovery time to platelet count greater than 50000/microl was significantly affected by age; however, there were no significant differences in the recovery of WBC, neutrophils and platelets in relation to several parameters examined. CONCLUSION: These findings suggest that CD34-positive PBSCT may facilitate stable hematopoietic recovery after HDCT in patients with advanced GCT, and that HDCT, if combined with PBSCT, could be performed with comparative safety in such patients, irrespective of their individual characteristics.