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.

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).

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.

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.

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.

[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.

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.

[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.

Benign metachronous bilateral ovarian and mediastinal teratomas with an elevated alpha-fetoprotein.

Teratomas are a common form of non-seminomatous germ cell tumor histologically composed of tissues derived from multiple cell lines of the primary embryonic germ cell layers. There are few cases reported in the literature that describe multiple locations with recurrence of benign teratomas, none of which describe an elevated AFP. We describe a case of metachronous bilateral recurrent ovarian and mediastinal teratomas with a curiously elevated α-fetoprotein. We may be describing a novel syndrome of recurrent metachronous teratomas. Because of the uncertainty of this case, the patient will require close follow-up over the next several years.

[Initial experience in intraoperative radiolocalization of the parathyroid adenoma with freehand SPECT and comparative assessment with portable gamma-camera]. / Experiencia inicial en la radiolocalización intraoperatoria del adenoma paratiroideo con freehand SPECT y valoración comparativa con gammacámara portátil.

Initial experience is presented by using freehand SPECT in the intraoperative radiolocalization of a parathyroid adenoma in 2 patients, one which was mediastinal. There is only one previous publication including 3 patients with parathyroid adenomas in usual parathyroid localizations. We also report for the first time a comparative assessment of results with portable gammacamera during the same surgery. In the operating room, we obtained images with portable gamma-camera and 3 D reconstruction with freehand SPECT from 15 min after iv injection of 5 mCi of (99m)Tc-MIBI. Both devices enabled the 2 adenomas to be detected intraoperatively, as well as checking activity of the excised gland and absence of significant uptake in surgical bed, with confirmation by intraoperative pre-postsurgical PTH levels, pathology and clinical follow-up for 10 months. Both devices accurately located the parathyroid adenomas intraoperatively, as well as confirmation of their extirpation, but freehand SPECT provided additional information of adenoma depth (mm) from the skin border, very useful for minimally invasive radio-guided surgery.

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).

Excision of ectopic mediastinal parathyroid adenoma via parasternal videomediastinoscopy.

Mediastinum is one of the place in which ectopic parathyroid adenomas can be located.Here, an ectopic mediastinal parathyroid adenoma, which was excised via parasternal videomediastinoscopy was presented. The patient with chronic renal insufficiency had increased calcium levels persistence after the surgery for cervical parathyroid adenoma.Radiologic and scintigraphic examinations revealed a focal intense nodule in anterior mediastinum. Parasternal videomediastinoscopy was performed via parasternal incision through the second intercostal space. Ex-vivo specimen radioactivity measurements and frozen examination confirmed parathyroid adenoma. Calcium levels were decreased dramatically after the operation. Parasternal videomediastinoscopy could be an alternative surgical way in anterior mediastinal small masses such as ectopic parathyroid adenoma. It is the first case in which parasternal videomediastinoscopy was used for excision of mediastinal parathyroid adenoma.