Malignant Mediastinal Tumors Research Articles

The Diagnosis and Multimodality Treatment of Malignant Mediastinal Tumors

縦隔原発悪性腫瘍の併存症を含めた病態は多様であり，その診断と治療戦略は疾患ごとの腫瘍学的特性により異なる．本総説では，外科治療を中心とした集学的治療を要することが多い悪性縦隔腫瘍である胸腺腫・胸腺癌・胸腺神経内分泌新生物，および悪性縦隔胚細胞性腫瘍に対する，それぞれの診断と外科治療，薬物療法，および放射線治療などに関して，診療ガイドラインや臨床試験，臨床研究の取り組みなどを解説し，特徴的な併存症についても述べる．

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

IntroductionThe 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). MethodsData 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. ResultsThe 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. ConclusionsOur 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.

Application of Artificial Intelligence in the Diagnosis, Treatment, and Prognostic Evaluation of Mediastinal Malignant Tumors.

Artificial intelligence (AI), also known as machine intelligence, is widely utilized in the medical field, promoting medical advances. Malignant tumors are the critical focus of medical research and improvement of clinical diagnosis and treatment. Mediastinal malignancy is an important tumor that attracts increasing attention today due to the difficulties in treatment. Combined with artificial intelligence, challenges from drug discovery to survival improvement are constantly being overcome. This article reviews the progress of the use of AI in the diagnosis, treatment, and prognostic prospects of mediastinal malignant tumors based on current literature findings.

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.

An unusual case of superior vena cava syndrome

Superior vena cava syndrome (SVCS) is a medical emergency, which in 80% of cases is caused by malignant mediastinal tumours. However, non-malignant causes lead to 20% of cases of SVCS.[1][1] We present an interesting case of SVCS after receiving ChAdOx1 CoV-19 vaccine (AstraZeneca). A 52-year-old

Artificial reconstruction for a thymoma invading superior vena cava

Artificial reconstruction for a thymoma invading superior vena cava

SVC Syndrome in ICU: The Need of a Multidisciplinary Approach

Superior vena cava (SVC) syndrome, a potentially life threatening medical emergency, occurs due to SVC obstruction caused by extrinsic compression, intrinsic stenosis or thrombosis. Malignant mediastinal tumours account for more than 80% of cases of SVC syndrome. We hereby report a case of SVC syndrome who came with clinical features suggestive of SVC syndrome with dyspnea managed and diagnosed in the Intensive Care Unit with a multidisciplinary approach.

TCTAP C-004 Acute Coronary Syndrome Due to Coronary Artery Compression by a Malignant Mediastinal Tumor

TCTAP C-004 Acute Coronary Syndrome Due to Coronary Artery Compression by a Malignant Mediastinal Tumor

Management of severe hypertension due to lenvatinib in patients with advanced thymic carcinoma

Rationale:Thymic carcinoma (TC) is a malignant mediastinal tumor, and there are no established treatments for pre-treated patients with advanced TC. Recently, lenvatinib was approved for such patients in Japan, ahead of other countries. Higher dose lenvatinib may be more efficacious than conventional treatments, although many patients experience grade 3 hypertension. Therefore, lenvatinib dose reduction remains controversial in terms of efficacy and tolerability.Patient concerns:Case 1 involves a 72-year-old woman who underwent complete resection of TC and was taking cilnidipine and azilsartan for hypertension. Six years later, multiple lung metastases were observed, and lenvatinib was started. Case 2 involves a 60-year-old man with TC, and was taking amlodipine for hypertension. A chest computed tomography showed progression in primary and metastatic lesions, and the patient started lenvatinib.Diagnoses:In both patients, grade 3 hypertension was observed after the administration of lenvatinib.Interventions:In Case 1, lenvatinib dose was reduced 3 times because lenvatinib was not interrupted despite grade 3 hypertension. In contrast, in Case 2, lenvatinib was interrupted when grade 3 hypertension occurred and was resumed after a decrease in blood pressure to baseline.Outcomes:In Case 2, higher tumor regression may have been achieved because of the maintenance of a high dose of lenvatinib compared with that in Case 1.Lessons:Lenvatinib is a promising agent for advanced TC; however, hypertension should be addressed cautiously, especially at the outset of administration. Lenvatinib may have to be appropriately interrupted and resumed as soon as the blood pressure is controlled to maximize efficacy and minimize toxicity.

Mediastinal Tuberculoma Mimicking Malignant Cardiac Tumor: A Case Report

Background: The clinical manifestations of cardiac masses are diverse and lack specificity. Here we report a cardiac mass detected by transthoracic echocardiography. Multimodality imaging and pathological findings after the operation confirmed the mass as mediastinal tuberculoma. Case presentation: A 45-year-old male patient was admitted to our hospital reporting chest tightness, weight loss, and dyspnea for 3 months after exercise. Transthoracic echocardiography showed that there were a large number of pericardial effusions and a soft tissue mass measuring 7.7 cm × 4.5 cm in the upper mediastinum, which oppressed the right pulmonary artery and accelerated the blood flow of the left pulmonary artery. Contrast-enhanced ultrasonography showed degenerative inhomogeneous high enhancement of and an unclear boundary in the mass. Contrast-enhanced chest CT revealed punctate and patchy calcification in and uneven enhancement of the mass and the lymph nodes around the aortic arch. The mass was diagnosed as a malignant mediastinal tumor. Pathological analysis of the mass revealed chronic granulomatous tuberculosis. The symptoms abated significantly after antituberculosis treatment. The patient remained asymptomatic during follow-up. Conclusion: This report presents a rare case of mediastinal tuberculoma mimicking a malignant cardiac tumor. Multimodality imaging should be incorporated for differentiation of cardiac masses.

The incidence and prognosis of thymic squamous cell carcinoma: A Surveillance, Epidemiology, and End Results Program population-based study.

Background:Thymic carcinoma represents a rare type of malignant mediastinal tumor and has been the subject of controversy. Although independent prognostic factors related to thymic carcinoma have been investigated previously, few studies have focused specifically on the survival outcomes associated with thymic squamous cell carcinoma (TSCC). This study aims at presenting a survival analysis in this rare malignant disease at population level.Methods:We extracted the data of 216 patients with TSCC recorded from 1973 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The patients’ demographic features, clinical traits, and treatment factors were analyzed in order to identify prognostic factors, which correlate overall survival using the Kaplan–Meier method as well as a multivariate Cox regression model, for TSCC.Results:The majority of patients were male, Caucasian, married, and insured. Furthermore, 58.3%, 54.6%, and 59.7% of patients TSCC underwent surgery, radiotherapy, and chemotherapy respectively. In a multivariate analysis, age of diagnosis (hazard ratio [HR]: 1.022, 95% confidence interval [CI]: 1.003–1.040, P = .020), surgical treatment (HR: 0.282, 95% CI: 0.164–0.484, P = .000), and stage (regional vs distant HR: 0.532, 95% CI: 0.324–0.872, P = .013; localized vs distant HR: 0.297, 95% CI: 0.133–0.664, P = .003) correlated with increased overall survival, whereas adjuvant therapy, including chemotherapy and radiotherapy, did not correlate with survival. Among surgically treated patients, age of diagnosis and stage were associated with better overall survival, while chemotherapy and radiotherapy did not contribute significantly to overall survival.Conclusion:Surgery, age of diagnosis, and stage were associated with better overall survival among TSCC.

Clinical features and outcomes of surgical treatment of malignant mediastinal neurogenic tumors

Clinical features and outcomes of surgical treatment of malignant mediastinal neurogenic tumors

Mediastinal tumors of peripheral nerve origin (so-called neurogenic tumors).

The mediastinum can be the site of origin of a variety of benign and malignant tumors of peripheral nerve sheath origin. Although schwannoma is one of the most common tumors found in the posterior mediastinum, peripheral nerve sheath tumors are reported in all compartments of the mediastinum. The majority of peripheral nerve sheath tumors in the mediastinum as in other anatomic sites occur sporadically, and a subset of them, most notably neurofibromas, and to a lesser extent, schwannomas and malignant peripheral nerve sheath tumors, occur in patients with syndromes such as neurofibromatosis 1 (NF1). In this review, the characteristics of mediastinal nerve sheath tumors along with the histologic differential diagnosis are summarized. Primary emphasis is placed upon the use of morphologic criteria for establishing a definitive diagnosis with reference to photomicrographs to illustrate the classic and sometimes unusual features of this varied group of tumors. The judicious application of ancillary testing, most frequently immunohistochemistry, for separating peripheral nerve sheath tumors from each other and from their morphologic mimics is reviewed. Included in the review are the clinicopathologic features, clinical management and prognostic implications of benign and malignant mediastinal peripheral nerve sheath tumors.

Contrast-Enhanced Ultrasonography versus Contrast-Enhanced Magnetic Resonance Imaging in the Diagnosis of Mediastinal Tumors

The aim of the study was to evaluate and compare contrast-enhanced ultrasound (CEUS) and contrast-enhanced magnetic resonance imaging (CE-MRI) with respect to their value in the differential diagnosis between benign and malignant mediastinal tumors. Forty-two patients with mediastinal tumor underwent CEUS and CE-MRI respectively. The sensitivity, specificity, diagnostic coincidence rate, positive predictive value (PPV) and negative predictive value of the two methods were compared. The value of different enhancement patterns in the differential diagnosis of benign and malignant mediastinal tumors was analyzed. SonoLiver software was used to obtain the dynamic vascular pattern curve (DVPC) of the lesions, and parameters such as arrival time (AT), rise time (RT), time to peak (TTP), maximum intensity/peak intensity (IMAX) and quality of fit (QOF) were extracted from time–intensity curves for quantitative analysis. We found that (i) the specificity of CEUS was higher than that of CE-MRI, and the PPV and diagnostic coincidence rate of CEUS were equal to those of CE-MRI; (ii) the enhancement patterns and DVPC of CEUS differed between the benign and malignant groups, while there was no difference in CE-MRI enhancement intensity; and (iii) AT, RT and TTP in the malignant groups were significantly shorter, while IMAX was significantly higher. In conclusion, the application of quantitative parameters and DVPC of CEUS is worth popularizing. CEUS can be used as an effective alternative and complementary examination for patients who cannot undergo CE-MRI.

Multimodality treatment outcome in patients with primary malignant mediastinal germ cell tumor in adults.

BackgroundMalignant mediastinal germ cell tumor (MGCT) is rare and has poor outcomes even after multimodality treatment. Data from resource‐poor countries are scarce in the literature.AimsTo evaluate the clinicopathologic features and treatment outcome of primary malignant MGCT at our center.Methods and ResultsSingle institutional data review of patients aged ≥18 years, treated with a diagnosis of malignant MGCT between Nov'2013 and Nov'2019. Risk stratification was done as per International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Patients were treated with platinum based chemotherapy and surgical resection for the residual disease was performed in non‐seminomatous histology.28 patients had MGCT with a median age of 25 years (range:18‐36) and all were male. Seven patients had superior vena cava obstruction (SVCO) at diagnosis and pre‐treatment histological diagnosis was available in 23 (82%) patients. Seven (25%) patients had seminoma histology, all were of good risk as per IGCCCG risk criteria, whereas others had non‐seminoma histology with poor‐risk group. Seven patients with seminoma histology achieved a complete response after initial treatment. Six patients with non‐seminoma histology underwent complete resection of residual disease post‐chemotherapy and five revealed residual viable tumors. After a median follow‐up of 10.8 months (range:2.9‐75), 3‐year progression‐free survival (PFS) and overall survival (OS) estimate was 61.2% and 94.7% in the whole cohort, respectively and 3‐year PFS and OS estimate was 100% in patients with seminoma histology.ConclusionsThis is the largest data set of MGCT patients' outcomes reported from India with multi‐modality treatment. All patients were male and one‐fourth had SVCO at presentation. Seminoma histology patients had a 100% outcome after initial platinum based chemotherapy. But, those with non‐seminoma histology had a poor outcome even with chemotherapy and surgery.

Safe diagnostic management of malignant mediastinal tumors in the presence of respiratory distress: a 10-year experience

BackgroundThe fundamental treatment for patients with pediatric malignant mediastinal tumors is chemotherapy. Therefore, accurate diagnosis is essential for selecting the appropriate chemotherapeutic regimen. However, malignant mediastinal tumors occasionally cause respiratory distress, and biopsies under general anesthesia are dangerous for such patients as invasive mechanical ventilation can aggravate airway obstruction caused by mass effect. In this study, we reviewed our 10-year diagnostic experience to evaluate the efficacy of our practices and confirm a safe diagnostic protocol for future patients.MethodsWe retrospectively reviewed medical records of children with malignant mediastinal tumors diagnosed at Nagoya University Hospital from 2007 to 2018 who demonstrated respiratory distress. Respiratory distress included dyspnea, massive pleural effusion, wheezing, and hypoxemia owing to tumors. Data on sex, age at onset, primary symptoms, location of tumor, management strategy (especially the method of diagnosis and definitive diagnosis), clinical course, prognosis during the acute phase (within 3 months from the onset of respiratory symptoms), and long-term outcome were collected.ResultsTwelve pediatric patients met the review criteria. There were seven anterior mediastinal tumors and five posterior mediastinal tumors. All anterior mediastinal tumors were diagnosed via bone marrow smear, thoracentesis, or core needle biopsy while maintaining spontaneous breathing. Regarding posterior tumors, two patients were diagnosed via a core needle biopsy and lymph node excisional biopsy under spontaneous breathing. Two cases were initially diagnosed solely using tumor markers. One patient with severe tracheal compression underwent tumor resection with extracorporeal membrane oxygenation stand-by. No patient died of diagnostic procedure-related complications.ConclusionsIn 11 of the 12 cases reviewed, safe and accurate tumor diagnosis was accomplished without general anesthesia. A diagnostic strategy without general anesthesia considering the tumor location proved to be useful.

Successful Therapy on Patients with Yolksac and Embrional Carcinoma by Surgery and Chemotherapy

Background: Malignant mixed germ cell tumors account for 13-25% of all non seminoma germ cell tumors, almost all cases were found in males (85%), increased in the third decade, and had an average survival rate of 40-45%. With modern management the average 5-year survival rate can be over 80%.Case Report: We reported a case report in Saiful Anwar Malang Hospital, Indonesia, a young man, 26 years old with an malignant epithelial tumor derived from mediastinal or lung. The CT scan of the chest showed an lobulated solid mass of iso-hipodens on the anterior superior mediastinum, mass encompassing the aortic arch, left pulmonalis artery, subclavian artery. The result from transthoracic FNAB with USG guidance showed an malignant epithelial tumor derived from mediastinal or lung, impression of an adeno squamous carcinoma. The AFP, LDH, and NSE serum level was elevated. Patient underwent a surgical sternotomy and tumor debulking. The biopsy showed an malignant mixed germ cell tumor (yolksac and embrional carcinoma). These were confirming the diagnosis of malignant mixed germ cell mediastinal tumor (yolksac and embrinonal carcinoma). Patient received a combination bleomycin, etoposid, cisplatin 3 series chemoteraphy  and evaluated.Conclusion: Some procedures like biopsy, tumor marker, could differentiate the subtype of mediastinal germ cell tumor. The multimodality treatment by combining surgical therapy (surgical sternotomy and tumor debulking) with chemotherapy could increase the survival rate of patients.

Primary malignant mediastinal germ cell tumors: A single institutional experience.

Background:Primary mediastinal malignant germ cell tumour (PMMGCT) is rare with unsatisfactory prognosis and pose difficulty in management due to lack of guidelines.Methods:All cases of PMMGCT diagnosed and treated between years 2014 to 2018 were retrospectively evaluated for clinico-pathological features, multimodality treatment and follow up.Results:Among a total of five PMMGCT cases, three were seminomatous and two were non seminomatous tumour [Yolk- sac tumour (n-1) and Mixed tumour (n-1)]. Four of these cases were non - metastatic with locally advancement and another one presented with metastasis to supraclavicular lymph node. All patients received platinum based induction chemotherapy. Post-induction chemotherapy, two cases of non seminomatous tumours underwent surgery. Among the three seminoma cases, one patient showed complete metabolic response; one with metastasis succumbed to the disease and the in-operable case of seminoma received local radiotherapy.Conclusion:PMMGCT needs a multi-disciplinary approach for appropriate diagnosis and management. Clinicopathological features like tumour site, extension, histopathological type, tumour stage and serum tumour marker are necessary for prognostication and decision making of further treatment plan.

PD-L1 Expression and Tumor-Infiltrating Lymphocytes in Thymic Epithelial Neoplasms.

Thymic epithelial tumors (TETs) are rare malignant mediastinal tumors that are difficult to diagnose and treat. The programmed death 1 (PD-1) receptor and its ligand (PD-L1) are expressed in various malignant tumors and have emerged as potential immunotherapeutic targets. However, the immunobiology of TETs is poorly understood. We evaluated PD-L1 expression and the presence of tumor-infiltrating lymphocytes (CD8 and CD3 expression) in surgical TET specimens from 39 patients via immunohistochemistry and determined their relation to clinicopathological parameters. Cases with membranous reactivity of the PD-L1 antibody in ≥1% of tumor cells were considered positive. Positive PD-L1 expression was observed in 53.9% of cases. Histologically, PD-L1 expression was positive in 2/6 type A, 2/6 type AB, 3/9 type B1, 4/4 type B2, 5/6 type B3, and 5/8 type C TET cases. Thus, the number of cases with PD-L1 expression and the percent expression of PD-L1 were significantly higher in more aggressive thymomas (type B2 or B3). CD3+ and CD8+ tumor-infiltrating lymphocytes were diffusely and abundantly distributed in all cases. These data suggest that a PD-1/PD-L1 blockade is a promising treatment for TETs, with more beneficial treatment effects for aggressive thymomas such as type B2 or B3.

525P - Retrospective analysis of outcomes of cisplatin and irinotecan combination chemotherapy for unresectable thymic carcinoma

BackgroundThymic carcinoma is a rare, malignant mediastinal tumor originating from thymic epithelial cells. It exhibits a tendency for metastasis and invasive growth. Unresectable thymic carcinoma is treated with systemic chemotherapy. However, a definitive chemotherapeutic regimen for this entity is yet to be established. The objective of this study was to evaluate the efficacy and safety of cisplatin and irinotecan combination as the first-line chemotherapy. MethodsData pertaining to patients with advanced thymic carcinoma who received cisplatin and irinotecan combination chemotherapy between January 1, 2002 and December 31, 2018, were retrospectively analyzed. The end points were disease control rate, progression free survival, and overall survival. The incidence of significant hematological and non-hematological toxicity was also assessed. ResultsWe identified 17 patients with a median age of 56 years (ECOG performance status: 0 or 1). All patients had clinical stage (Masaoka-Koga staging system) IVa or IVb. Disease control was achieved in 15 patients (88.2%). Median progression-free survival was 7.3 months [95% confidence interval (CI) 2.7–11.6]; median overall survival was 45.6 months (95% CI 9.49–69.5). The outcomes were similar to those achieved with previously reported chemotherapy regimen, CBDCA plus paclitaxel or Cisplatin combination chemotherapy. No treatment-related deaths occurred in this cohort. Grade 3 or worse hematological toxicity was observed in five patients (neutropenia: three patients; anemia: two patients); grade 3 or worse non-hematological toxicity was observed in three patients. None of the patients developed febrile neutropenia. ConclusionsCisplatin and Irinotecan combination chemotherapy may be a safe and effective first-line chemotherapy regimen for unresectable thymic carcinoma. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureY. Hosomi: Honoraria (self): AstraZeneca. All other authors have declared no conflicts of interest.