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Objective: Rural-urban healthcare disparities have been demonstrated throughout the United States, particularly in acquiring oncologic care. In this study, we aim to discern the role of rural-urban health disparities in thymic cancer incidence and uncover potential survival disparities., Methods: The Surveillance, Epidemiology, and End Results (SEER) 17-State database was queried for all cases of thymoma (ICD-O-3/3 codes: 8580-8585) and thymic carcinoma (8586) located in the thymus (primary site code C37.9) diagnosed between 2000 and 2020. Residence was established using SEER Rural-Urban Continuum Codes. Incidence trend modeling for rural versus urban patients was completed using Joinpoint Regression Software. Chi-square, Kaplan-Meier with log-rank testing, and Cox proportional hazards was completed using SPSS, with significance set to p <0.05., Results: Joinpoint analysis revealed a significant growth in incidence in the urban population compared to a stagnant incidence among the rural population. Disease specific survival was higher among urban patients on univariate modeling (p = 0.010), and confirmed on multivariate analysis, whereby rural living conferred an adjusted hazard ratio of 1.263 (95 % CI 1.045-1.527; p = 0.016) in comparison to urban patients., Conclusions: These findings demonstrate differences between thymic cancer incidence and outcomes in patients living in urban versus rural environments and demonstrate an important disparity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Little is known about the aetiology of thymoma. This study aims to identify medical risk factors for thymoma as a systematic approach to new hypotheses on the aetiology of this disease. A European multi-centre case-control study was conducted from 1995 to 1997, including incident cases aged 35-69 years with thymoma. Altogether, we accepted 85 cases and 3350 controls, of which we interviewed 77 cases and 2071 population controls about constitutional factors, medical examinations, and former diseases. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated. Medical examinations with X-ray or radiotherapy performed >20 times at least one year before the thymoma diagnosis indicated a possible risk factor for thymoma (OR 1.58, 95% CI 0.93-2.69). Having the first radiotherapy treatment at least one year before the thymoma diagnosis yielded an OR for thymoma of 2.39; 95% CI (0.96-5.99), and if it was at least five years before, the OR for thymoma was 2.81; 95% CI (1.03-7.72). Having a red/auburn hair colour was associated with thymoma, (OR 3.6, 95% CI 1.4-9.5) whereas having pigmented skin was slightly associated with thymoma (OR 1.8, 95% CI 0.8-3.8). Over twenty instances of X-ray examinations or radiotherapy were identified as potential risk factors for thymoma, along with certain constitutional factors. The observed correlations between benign tumours and thymoma could stem from an inherent predisposition to tumour development or result from detection bias. Given that this is the initial analytical study examining medical risk factors for thymoma, all of the results should be approached with caution, acknowledging the possibility that some findings might be incidental.

Introduction: Thymic epithelial tumors (TETs) are rare neoplasms often associated with immune-related disorders. Patients with Good's syndrome (GS), an adult-acquired TET-related immunodeficiency, are at a high risk of mortality due to infectious diseases. This study aims to examine COVID-19 occurrence and severity in TET patients, with or without GS., Methods: Clinical records of TET patients referred to the Regional Coordinating Center for Rare Tumors of Campania Region were retrospectively collected. During the observation period, elapsing from March 2020 to April 2023, the following data were collected: occurrence of SARS-CoV-2 infection; COVID-19 severity, according to the National Institute of Health (NIH) illness categories; COVID-19 treatment. COVID-19 occurrence and severity were assessed in the overall population and correlated with the presence of GS and/or other immune-related dysregulations., Results: Overall, 47 TET patients were included in the study; 27 of these (57.4%) had GS. All participants had received a full cycle of mRNA vaccine for SARS-CoV2., Thirty-one patients (66.0%) experienced COVID-19, of whom 18 (58.0%) had previously received a diagnosis of GS. No significant association of GS and/or other immune-related dysregulations with SARS-CoV-2 infection occurrence was detected (Fisher's exact test p = 1 and p = 0.3587, respectively). Among patients with GS, 8 (45.0%) reported a COVID-19 severity score of ≥ 3; whereas, only 1 of the 13 patients without GS (7.7%) had a severity score of ≥ 3. The correlation between presence of GS and COVID-19 severity (score 1 or 2 vs. ≥ 3) was statistically significant (p = 0.0448). No statistically significant association between COVID-19 severity and other immune-related syndromes were found (p = 1). Of note, all the hospitalized patients for NIH 4 and 5 COVID-19 had GS., Conclusions: Our data suggest that TET patients, especially those with GS, require a careful multidisciplinary monitoring for SARS-CoV-2 infection, in order to establish tailored treatments and prophylactic protocols., (© 2024. The Author(s).)

Objectives: Thymic carcinoma and thymic neuroendocrine tumor (NET) are rare and are more likely to develop second malignancies. The purpose of this study was to explore the incidence and lifetime risk of second malignancies in thymic carcinoma and thymic NET., Methods: The standardized incidence ratio (SIR) and the age-adjusted cancer incidence of the thymic carcinoma and thymic NET patients with second malignancies were retrospectively calculated by using the Surveillance, Epidemiology, and End Results (SEER) database. Prognosis results were also determined by Kaplan-Meier analysis and Cox regression., Results: 1130 patients with thymic carcinoma (73 patients had second malignancies) and 263 patients with thymic NET (19 patients had second malignancies) from 2000 to 2018 are included. Patients with thymic carcinoma (SIR: 1.36, 95% CI 1.08-1.69) and with thymic NET (SIR: 1.73, 95% CI 1.13-2.54) demonstrate an increased overall risk of developing second malignancies in various organ systems. The age-adjusted cancer incidence of second malignancies in patients with thymic carcinoma is 3058.48 per 100,000 persons (4178.46 per 100,000 persons in patients with thymic NET). Age at diagnosis is a significant risk factor for the development of second malignancies., Conclusion: The incidence of second malignancies in patients with thymic carcinoma and thymic NET is significantly higher than the patients in the normal population. The occurrence of second malignancies is not related to the use of different treatments. It is important to extend the follow-up period and add other screening methods., (© 2024. The Author(s).)

Introduction: The effects of socioeconomic factors on patients diagnosed with thymomas have not been previously studied. We propose these factors have an important association with survival. Thymoma is the most common tumor of the anterior mediastinum. Compared to other neoplasms which can integrate different therapeutic approaches for treatment, the most effective therapy for local and locally advanced thymoma is complete surgical resection. This study aimed to elaborate on socioeconomic variables and their potential effects on the survival outcomes in patients diagnosed with thymoma., Methods: Clinical data from the Surveillance, Epidemiology, and End Results 22 registry from 1975-2019 was used to define overall and cancer-specific survival of thymoma. The unadjusted analysis was followed by fitting a Cox proportional hazards model that included all variables assessed with Kaplan-Meier curves. An unadjusted Kaplan-Meier analysis was performed first comparing time to death by decade, age, race, ethnicity, sex, income, and region separately. The primary outcome was survival measured in months., Results: We identified 1821 patients aged 18 y or over from the Surveillance, Epidemiology, and End Results database with a thymoma diagnosis between the years 1975 and 2019. The demographic variables considered were age, race, ethnicity (Hispanic/non-Hispanic), sex (male/female), inflation-adjusted income in 2019 dollars, and community size. We observed a decrease in mortality from thymic neoplasm across the decades. For each subsequent year, mortality risk decreased by 3.5% (P <0.001). The mortality risk of older patients was significantly higher. Compared to the youngest group, the mortality risk was 52.8% higher in the 50-year-old to 65-year-old category (P = 0.021). The mortality risk was 339% times higher in the 65 + age group (P <0.001). Income may be associated with risk reduction. Patients making greater than $75,000 had a 40.1% lower mortality risk than those making less than $50,000 (P = 0.029). The survival rate categorized by race was similar between Blacks and Whites but tended to be higher for the Asian and Pacific Islander groups without reaching statistical significance (P = 0.12)., Conclusions: Medical advancements have improved the overall thymoma survival in the past four decades. Yet, demographic, and socioeconomic factors such as age, income, and race may also play a role., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Thymic carcinoma (TC) is a rare malignant tumor that can have a poor prognosis, and accurate prognostication prediction remains difficult. We aimed to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) based on a large cohort of patients., Methods: The Surveillance Epidemiology and End Results (SEER) database was searched to identify TC patients (1975-2016). Univariate and multivariable Cox regression analyses were used to identify predictors of OS and CSS, which were used to construct nomograms. The nomograms were evaluated using the concordance index (C-index), calibration curve, receiver operating characteristic curve, and decision curve analysis (DCA). Subgroup analysis was performed to identify high-risk patients., Results: The analysis identified six predictors of OS (Masaoka stage, surgical method, lymph node metastasis, liver metastasis, bone metastasis, and radiotherapy) and five predictors of CSS (Masaoka stage, surgical method, lymph node metastasis, tumor size, and brain metastasis), which were used to create nomograms for predicting three-year and five-year OS and CSS. The nomograms had reasonable C-index values (OS: 0.687 [training] and 0.674 [validation], CSS: 0.712 [training] and 0.739 [validation]). The DCA curve revealed that the nomograms were better for predicting OS and CSS, relative to the Masaoka staging system., Conclusion: We developed nomograms using eight clinicopathological factors that predicted OS and CSS among TC patients. The nomograms performed better than the traditional Masaoka staging system and could identify high-risk patients. Based on the nomograms' performance, we believe they will be useful prognostication tools for TC patients.

Background: Thymic malignancies are rare tumors about which data are limited. Our objective here was to evaluate the outcomes and risk factors for complications and death in patients who underwent extended surgery to remove thymic malignancies., Methods: We retrospectively included patients who underwent extended resection of locally advanced, nonmetastatic thymic malignancies at our institution. Patients were deemed eligible for resection by a multidisciplinary team. During surgery, priority was given to achieving complete resection rather than to sparing organs., Results: The 108 patients had a mean age of 53 ± 15 years (range, 9-83); among them, 91 had thymoma, 12 thymic carcinoma, and 5 neuroendocrine tumor. The Masaoka stage was III or higher in 86 patients; examination of operative specimens resulted in downstaging of 22 patients. Tumor-free resection margins were achieved in 98 patients. Overall 5- and 10-year survival rates were 80% and 68%, respectively. Myasthenia gravis, present in 36 patients, was the only independent significant risk factor for major postoperative complications. Age older than 70 years, thymic carcinoma or neuroendocrine tumor, pT3 or pT4 stage, and R1 or R2 resection margins independently predicted death. The number of resected structures was not associated with survival. Thymic carcinoma or neuroendocrine tumor was independently associated with shorter disease-free survival., Conclusion: In an expert center, extended resection targeting complete resection rather than organ preservation provided good outcomes in patients with locally advanced thymic malignancies. The risk/benefit ratio of surgery should be assessed with special care in patients who are elderly or have myasthenia gravis., Competing Interests: Declaration of Competing Interest OM board member fees from Astra Zeneca (lung cancer)., (Copyright © 2023 SPLF and Elsevier Masson SAS. All rights reserved.)

Objective: Thymic epithelial tumors (TETs) are rare tumors that originated from thymic epithelial cells, with limited studies investigating their prognostic factors. This study aimed to investigate the prognostic factors of TETs and develop a new risk classifier to predict their overall survival (OS)., Methods: This retrospective study consisted of 1224 TETs patients registered in the Surveillance, Epidemiology, and End Results (SEER) database, and 75 patients from the First Affiliated Hospital of Xi'an Jiaotong University. The univariate and multivariate Cox regression analyses were adopted to select the best prognostic variables. A nomogram was developed to predict the OS of these patients. The discriminative and calibrated abilities of the nomogram were assessed using the receiver operating characteristics curve (ROC) and calibration curve. Decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI) were adopted to assess its net clinical benefit and reclassification ability., Results: The multivariate analysis revealed that age, sex, histologic type, TNM staging, tumor grade, surgery, radiation, and tumor size were independent prognostic factors of TETs, and a nomogram was developed to predict the OS of these patients based on these variables. The time-dependent ROC curves displayed that the nomogram yielded excellent performance in predicting the 12-, 36- and 60-month OS of these patients. Calibration curves presented satisfying consistencies between the actual and predicted OS. DCA illustrated that the nomogram will bring significant net clinical benefits to these patients compared to the classic TNM staging system. The estimated NRI and IDI showed that the nomogram could significantly increase the predictive ability of 12-, 36- and 60-month OS compared to the classic TNM staging system. Consistent findings were discovered in the internal and external validation cohorts., Conclusion: The constructed nomogram is a reliable risk classifier to achieve personalized survival probability prediction of TETs, and could bring significant net clinical benefits to these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Jiang, Zhao, Shi, Ma, Fu, Liang, Tian, Ruan and Yao.)

Objectives: Thymic epithelial neoplasms (TENs) represent a heterogeneous group of rare thoracic malignancies. We analysed the clinicopathological features, survival outcomes, risk factors, and patterns of recurrence in patients undergoing resection., Methods: Records were reviewed for adult patients with TEN who underwent resection from 2006 to 2019. Survival rates were assessed using the Kaplan-Meier method. Univariable and multivariable analyses were performed using the log-rank test and Cox proportional hazards model., Results: A total of 100 patients were analysed (51 females, median age 58 years). Thymoma was the most common histology (n = 92), followed by thymic carcinoma (n = 5) and thymic neuroendocrine tumour (n = 3). Stage II (Masaoka) tumours were most common (n = 51), followed by stage I (n = 27). World Health Organization B2/B3 was the most prominent histological subtype (n = 34). Complete resection (R0) was achieved in 91 patients: 86/92 thymoma, 4/5 thymic carcinoma and 1/3 neuroendocrine tumour. The most common treatment modality was surgery alone in 72 patients, followed by surgery and radiation therapy in 24, and adjuvant chemoradiotherapy in 3 patients. Only one patient with thymic carcinoma received neoadjuvant chemotherapy. The 10-year overall and disease-free survival rates were 86.6% and 83.9%, respectively. Recurrence was most common in neuroendocrine tumours (3/3). Risk factors for recurrence identified on multivariable analyses were: R1/2 resection (hazard ratio 9.30; 95% confidence interval 1.82-36.1), TEN subtype (hazard ratio 8.08; 95% confidence interval 1.24-34.6), and presence of lymphovascular invasion (hazard ratio 9.56; 95% confidence interval 2.56-25.8)., Conclusions: Complete resection remains critical in patients with TEN. Incomplete resection, high-risk histology, and lymphovascular invasion highlight the need for effective adjuvant modalities. Given the rarity of these diseases, emphasis must be placed on collaborative research conducted on TEN., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Thymic carcinoma is a rare neoplasm, and its prognosis is very poor. The purpose of this study was to validate the clinical and epidemiological factors, diagnosis and initial treatment of thymic carcinoma among all patients diagnosed in the registered hospital group., Methods: We surveyed retrospective data from 152,921 cancer patients in 22 principal hospitals., Results: A total of 88 thymic carcinoma cases were newly diagnosed. These patients were 50 men and 38 women, with a median age of 66 years old. Eight patients were discovered in cancer screening, 9 in a voluntary setting, 14 at health checkups, 25 at follow-up of other diseases, and 32 cases by introduction from another hospital. Only 14 cases had been diagnosed with localized disease, but 5 cases were accompanied by regional lymph node metastasis. Furthermore, 12 cases showed infiltration into adjacent organs, and 24 cases had distant metastasis. Eighty-three cases were diagnosed by a pathological diagnosis. A surgical approach, chemotherapy, and radiotherapy were performed for 29, 35 patients, and 31 patients, respectively, while 17 patients received best supportive care., Conclusion: The diagnosis of thymic carcinoma is still difficult, and this disease has a tragically rapid progression if when discovered during follow-up of other diseases. An innovative modality for the early detection of thymic carcinoma is needed in modern medical society., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The possibility of recurrence in COVID-19 is very rare and hence mostly underdiagnosed. In the face of pandemic, this can lead to circulation of the virus like a hidden iceberg. Better understanding about this topic can improve our knowledge of the COVID-19 pathogenesis and ways to control the transmission., Case Presentation: A 41 year old male with no known comorbidities was admitted five times during a period of 7 months each time after being detected RTPCR positive for SARS-CoV-2 and more symptomatic than previously. He had no contact with other COVID-19 patients and was asymptomatic in between admissions. Despite this, he did not develop antibodies against SARSCoV-2. Later on, he was diagnosed with thymoma on biopsy of the anterior mediastinal mass. Patient's condition deteriorated on last hospitalization and he died, despite the treatment. Here we present an interesting report on multiple times recurrent COVID-19 infection, probably a case of reactivation and different plausible explanations on the role of thymoma.;Conclusion: Acknowledging the potential of SARS-CoV-2 to cause recurrence is very important during the pandemic as a part of the long term transmission mitigation. The case report shows that previous infection does not guarantee complete immunity from COVID-19, especially in immuno-compromised patients. Hence, despite the status of prior infection, vulnerable individuals who recovered from COVID-19 should be under surveillance., (© Journal of the Association of Physicians of India 2011.)

Thymoma is the most common primary mass in anterior mediastinum. Although associated with low malignancy, it is often accompanied by myasthenia gravis resulting in poor prognosis. Due to the dual factors of tumor immune tolerance and autoimmune reaction, it is urgent to understand the immune status of MG with thymoma. In this study, RNA sequencing data were obtained from the TCGA and GEO cohorts to identify differentially expressed messenger RNAs and infiltrated immune cells. A total of 121 samples in TCGA and 43 samples in GEO were screened out. The infiltrated immune cells were identified by CIBERSORT, in which Tfh cells and activated DC cells were abnormal in thymoma patients. The differently expressed genes were performed by package LIMMA. The functional characteristics of differently expression genes were analyzed by GO and KEGG; one GO and seven KEGG pathways were both found in both TCGA and GEO cohorts. Meanwhile, 27 common differently expressed genes were obtained and were displayed by a Venn diagram. The TRRUST was used to screen the hub genes for the common 27 different genes and 6 genes were found. Then, PPI networks were constructed. Subsequently, the relationship between SCNAs of common genes and related immune cells tested by TIMER. Kaplan-Meier plots, ROC curve and Cox's expression model for immune infiltration and hub genes were also tested. In conclusion, we found that two types of immune infiltrated cells and six hub genes can predict the occurrence of myasthenia gravis in thymoma patients.

Thymomas are the most frequent adult mediastinal cancers. Their etiology is unknown and their pathogenesis poorly understood. Racial, ethnic and environmental factors influence tumorigenesis in many cancers, but their role in thymomas remains unclear to date. In this study that included pretreatment thymoma cases from India and Germany ( n = 37 and n = 77, respectively) we compared i) the prevalence of the thymoma-specific chromosome 7 c.74146970T > A mutation of the GTF2I gene in type A and AB thymomas; ii) epidemiological features; and iii) the frequency of myasthenia gravis (MG). Due to a known predominance of GTF2I mutation in A and AB histotypes, we included only a marginal number of type B thymomas as a control group in both cohorts. While the distribution of histological types between the cohorts was similar ( p = 0.1622), Indian patients were strikingly younger ( p < 0.0001; median age 50 vs. 65 years) and showed significantly lower tumour stage (Masaoka-Koga stage I) at primary diagnosis ( p = 0.0005) than the German patients. In patients with known MG status ( n = 17 in Indian and n = 25 in German cohort), a clear trend towards more frequent MG was observed in the Indian group ( p = 0.0504; 48 vs. 82%). The prevalence of the GTF2I mutation (analysed in n = 34 Indian and n = 77 German patients) was identical in the two cohorts. We conclude that racial-ethnic and environmental factors do not significantly influence the most common molecular feature of thymomas but may have an impact on the timing of clinical presentation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jain, Guleria, Singh, Parshad, Kumar, Gaiser, Kurz, Ott, Porubsky, Preissler, Sauer, Schölch, Ströbel, Hielscher, Marx and Popovic.)

Objectives: Lymph node dissection (LND) and nodal metastases in thymomas remain controversial and understudied. The aim of our study was to evaluate the incidence of nodal metastasis and the short term outcomes of systematic LND in thymomas., Material and Methods: From December 2017 to September 2020, we performed 54 LND conducted according to the International Thymic Malignancy Interest Group (ITMIG) lymph node map. This group was compared to a historical control group of 55 patients who underwent surgery in our center from January 2015 to November 2017., Results: LND was performed in 72 % and in 5 % of the cases in the study cohort group and historical control group, respectively. The number of lymph nodes retrieved was significantly higher in the study cohort group (3.89 per patient vs. 1.62, p = 0.0021). In the whole population studied, nodal metastases were found in 3 patients (2.8 % of all patients) with 5.6 % in the cohort study group vs. 0 % in the control group (p = 0.12). Patients with nodal metastasis had larger tumors (> 7 cm), and a higher histology grade (B2 and B3). There was a trend towards higher risk of laryngeal nerve palsy in the cohort study group (9.3 % vs. 1.8 %, p = 0.11)., Conclusion: Systematic LND increases the number of lymph node harvested and detects more lymph node metastases, which remains infrequent in thymomas. The impact of LND and the true prognostic significance of lymph node metastases remains controversial. Given the potential complications, LND or sampling should not be perfomed in small, encapsulated and low grade thymomas., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, it is not clear whether thymoma recurrence or unresectable lesions entail a worse prognosis of MG., Methods: This multicenter study was based on data from a Spanish neurologist-driven MG registry. All patients were aged >18 years at onset and had anti-acetylcholine receptor antibodies. We compared the clinical data of thymomatous and nonthymomatous patients. Prognosis of patients with recurrent or nonresectable thymomas was assessed., Results: We included 964 patients from 15 hospitals; 148 (15.4%) had thymoma-associated MG. Median follow-up time was 4.6 years. At onset, thymoma-associated MG patients were younger (52.0 vs. 60.4 years, p < 0.001), had more generalized symptoms (odds ratio [OR]: 3.02, 95% confidence interval [CI]: 1.95-4.68, p < 0.001) and more severe clinical forms according to the Myasthenia Gravis Foundation of America (MGFA) scale (OR: 1.6, 95% CI: 1.15-2.21, p = 0.005). Disease severity based on MGFA postintervention status (MGFA-PIS) was higher in thymomatous patients at 1 year, 5 years, and the end of follow-up. Treatment refractoriness and mortality were also higher (OR: 2.28, 95% CI: 1.43-3.63, p = 0.001; hazard ratio: 2.46, 95% CI: 1.47-4.14, p = 0.001). Myasthenic symptoms worsened in 13 of 27 patients with recurrences, but differences in long-term severity were not significant. Fifteen thymomatous patients had nonresectable thymomas with worse MGFA-PIS and higher mortality at the end of follow-up., Conclusions: Thymoma-associated MG patients had more severe myasthenic symptoms and worse prognosis. Thymoma recurrence was frequently associated with transient worsening of MG, but long-term prognosis did not differ from nonrecurrent thymoma. Patients with nonresectable thymoma tended to present severe forms of MG., (© 2021 European Academy of Neurology.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The purpose of this study was to clarify the prevalence, clinical features and survival of patients with thymoma and non-myasthenia gravis autoimmune disease (NMAD) using a nationwide cohort., Methods: The Japanese Association for Research on the Thymus nationwide database, which includes data from 32 institutions, was examined to clarify the prevalence and characteristics of NMAD associated with thymomas and elucidate the prognostic impact of NMAD for thymoma patients., Results: Among the 2423 patients with thymomas who were surgically treated between 1991 and 2010, 114 (4.7%) were identified with NMAD. The most frequently observed NMAD was pure red cell aplasia (PRCA) in 44 (1.8%), followed by hypogammaglobulinaemia (0.5%) and rheumatic arthritis (0.5%). Twenty-eight percent of patients with NMAD had concomitant myasthenia gravis. The presence of NMAD was not an independent prognostic factor for overall survival (OS) irrespective of the type of NMAD [PRCA+: hazard ratio (HR) 1.99, 95% confidence interval 0.74-4.47; PRCA- NMAD: HR 1.28, 0.30-3.56]; however, there were more cases with advanced age and disease of the thymoma amongst PRCA+ patients and these showed a worse OS than patients with PRCA- NMAD (P < 0.001), who had an OS similar to those without NMAD (P = 0.489). The 10-year OS rates in PRCA+, PRCA- NMAD and NMAD- groups were 45.5%, 97.4% and 89.5%, respectively. The main causes of death in PRCA+ patients were the progression of thymoma and other diseases including pneumonia., Conclusions: Although the presence of NMAD itself did not significantly affect survival after surgery for thymoma, the type of NMAD was associated with different clinical features and prognosis. The NMAD+ thymomas should be separately categorized according to the presence or absence of PRCA., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Extra-appendicular neuroendocrine tumors (NETs) are very rare tumors. While diagnostic and therapeutic guidelines are well established for adults, data on children and adolescents are lacking., Patients and Methods: Patients with a diagnosis of extra-appendicular NET registered on the Tumori Rari in Età Pediatrica - Rare Tumors in Pediatric Age (TREP) from 2000 to 2020 were analyzed. Clinical characteristics including patients' presentation, tumor features, treatment, and outcome were reviewed., Results: Twenty-seven patients with extra-appendicular NET registered on TREP with a median age of 173 months. The primary site was the pancreas (12) or bronchi (10) in the majority of cases. Other primary sites included the thymus, Meckel's diverticulum, and liver. Thirteen (48%) of tumors extended beyond the organ of origin: four invaded neighboring organs and/or regional nodes and nine involved distant metastases. The 3-year event-free survival (EFS) for those with localized disease was superior to those with metastatic disease (66.6% 95% CI 5-95% vs 33% 95% CI 5-68%, respectively; P = .005). A complete resection was feasible in 17 patients. The 3-year EFS in these patients was superior to those with no or incomplete resection (R0 vs R1/R2, respectively; P = .007). Overall, 16 children had no evidence of disease at follow-up, and one is alive with disease; five died, and five were lost to follow-up., Conclusions: Data from our experience demonstrated a wide heterogeneity of presentation and outcome of these tumors. Localized disease and complete surgical resection were the main prognostic factors of good outcome. Other therapies may have a role in prolonging survival in metastatic disease., (© 2021 Wiley Periodicals LLC.)

Competing Interests: Disclosures EB has received honoraria from Novartis, Ipsen and Pfizer, research grants from Novartis and he is a member of Ipsen and Novartis speaker's bureau; MC has received research funding and speaker/advisory board honoraria from Ipsen, Novartis, Lexicon and AAA-Pharma; RGC has reported being an advisory board member for Novartis, Ipsen, AAA-Pharma and Pfizer and has received research grants from Pfizer; NF has received honoraria from Novartis, Ipsen, Pfizer, AAA-Pharma, Merck Sharp & Dohme and Merck Serono and research grants from Novartis and Merck Serono; PF has reported advisory board for Novartis, Ipsen, Merck Serono, Pfizer, Lexicon and Italfarmaco and has participated at steering committee for Novartis, Ipsen and Merck Serono; AF is a member of speaker's bureau and has received honoraria from Ipsen, Novartis and Sirtex and has received research grants from Novartis; WWdH has received research grants from Ipsen; DH has received honoraria from Novartis, Ipsen, Pfizer and ROTOP Pharmaka GmbH and research grants from Ipsen and he is a member of Ipsen and Novartis speaker's bureau; UK has received research funding and speaker advisory board honoraria from Ipsen and Novartis; CLB has reported being an advisory board member for Novartis, Pfizer, Ipsen and AAA-Pharma; MP has reported being an advisory board member for and received honoraria from Novartis, Ipsen, Pfizer and Lexicon and has received research grants from Ipsen and Novartis; AB is a member of Novartis speaker's bureau; all other authors have declared no conflicts of interest.

Background: A proportion of thymoma-patients without a history of myasthenia gravis (MG) before thymectomy, appears to have positive anti-AChR-antibodies in the serum. These subclinical MG-patients could be underdiagnosed because analyzation of anti-AChR-antibodies in thymomas is not always performed in patients who did not experience neurological symptoms. The prevalence and long-term outcomes of subclinical MG are never described in literature yet., Methods: We retrospectively analyzed 398 consecutive patients who underwent a robotic-assisted thoracoscopic surgery at the Maastricht University Medical Center+ (MUMC+) between April 2004 and December 2018. In the MUMC+, a robotic approach is the standard surgical approach in patients with thymic diseases. Inclusion criteria were thymomas, thymectomy performed in the MUMC + with a follow-up of at least one year and age above 18 years old. Exclusion criteria were patients with thymic carcinomas, refused participation, or those who were lost to follow-up., Results: Of the 102 included thymoma-patients, 87 patients (85 %) were tested for anti-AChR-antibodies before thymectomy, of which 57 patients were diagnosed with clinical MG and seven subclinical MG-patients were found. Of the 15 patients who were not tested for anti-AChR-antibodies, four more subclinical MG-patients were discovered in the years after thymectomy. The median follow-up time was 62 months. In total, 11 subclinical MG-patients were found, with a mean age of 54 years and predominantly females (64 %). Ten subclinical MG-patients (91 %) developed clinical-MG, within six years after thymectomy. Immunosuppressive drugs were prescribed in five patients. Four patients were diagnosed with a recurrence of the thymoma. No surgical mortality was reported. Two patients died due to a myasthenic crisis., Conclusions: The prevalence of subclinical MG in thymomas was found to be 10.8 %. One in four patients who experienced no neurological symptoms before thymectomy, appeared to have anti-AChR-antibodies and 91 % of these patients developed clinical MG within six years after the thymectomy. Analyzing anti-AChR-antibodies in the serum is recommended in all suspected thymomas before a thymectomy is performed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: To assess the correlation of WHO histological classification and Masaoka-Koga staging system of thymic epithelial tumors (TETs) with prognosis., Methods: We retrospectively analyzed 83 patients with TETs in the Instituto Nacional de Enfermedades Neoplasicas between 1996 to 2018. We analyzed the clinical stages, histological types and treatment modalities and attempted to determine the impact on overall survival. The data was retrieved from clinical files and reviewed by a pathologist who reclassificated according to the 2004 WHO classification system. The staging was performed with the Masaoka-Koga staging system. Survival curves were constructed with Kaplan-Meir method., Results: There was a total of 83 patients with a median age of 55 years old included in the study. The histological type corresponded to thymoma (T) in 63.8% (n = 53) and to thymic carcinoma (TC) in 36.1%. T were type A, AB, B1, B2 and B3 in 14.4%, 18%, 12%, 3.6%, 7.4% of cases, respectively. The proportion of advanced disease (Masaoka stage III-IV) was high (65%). With a median follow-up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (P = 0.01). Univariate analysis showed that sex, histological type, clinical stage and surgery (P = 0.01) were significant independent prognostic factors. On multivariate analysis, histology type and Masaoka-Koga staging had an effect on survival., Conclusions: The results indicates a clear association between the WHO histological classification and Masaoka-Koga staging system with survival. We found a higher proportion of TETs with advanced disease at diagnosis. Further research are required and collaboration is important to foster knowledge focused on classification and treatment., Key Points: SIGNIFICANT FINDINGS OF THE STUDY: The WHO histological classification, the Masaoka-Koga system and surgery treatment were associated with overall survival., What This Study Adds: To determine prognosis factors in TETs., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Introduction: The Duke Myasthenia Gravis (MG) Clinic Registry is a disease-specific database containing physician-derived data from patients seen in the Duke MG Clinic since 1980., Methods: Data from 1060 MG patients initially seen between 1980 and 2008 were reviewed., Results: Fifty-four percent were male. Symptoms began after age 50 in 66% of males and 42% of females. Peak onset age in males was in their 60's; females had no predominant onset age. Onset age for both sexes increased from 1980 to 2008. Thymoma was present in 8.5%. Weakness was limited to ocular muscles for at least 2 y in 22% and became generalized later in 8.3% of these. Acetylcholine receptor antibodies were present in 78% overall, 82% with generalized MG and 52% with ocular MG (OMG). The distribution of MG disease class was similar in males and females, except that a greater proportion of women experienced myasthenic crisis and men were more likely to have OMG., Discussion: Data in the Registry permit comprehensive and longitudinal analysis of a validated MG population. Analysis of Registry data shows that the frequency of AChR antibody negative MG, ocular MG, and thymoma are similar to other reports, but the onset age and proportion of males have progressively increased compared to studies published more than 20 y ago. These observations demonstrate the value of collecting comprehensive clinical information and comparing historic and contemporary populations. Other potential uses of Registry data include comparison of outcome measures in different disease subgroups and the response to specific treatments., (© 2020 Wiley Periodicals LLC.)

Objectives: To summarize the clinical features of thymomatous myasthenia gravis (T-MG), examine the association between MG and thymoma, and identify the related factors or predictors for long-term prognosis of T-MG., Methods: A retrospective, observational study was conducted on 100 patients with T-MG and 96 patients with non-T-MG (NT-MG) between January 1, 2009 and December 31, 2019. The baseline characteristics were recorded for each patient. Logistic regression was used to measure the association between all clinical variables and T-MG prognosis., Results: Between the T-MG and NT-MG groups, age at onset (45.66 ± 11.53 years vs 39.06 ± 14.39 years); age >40 years (72.0% vs. 40.6%); AChR-Ab positive rate (100.0% vs. 83.3%); Myasthenia Gravis Foundation of America (MGFA) classification at the worst condition (≥grade III, 61.0% vs. 33.0%); thyroid dysfunction (7.0% vs. 20.8%); and outcome (complete stable remission + pharmacologic remission + improvement, 74.0% vs. 93.7%) were statistically significant (P < .05). Presence of thymoma (OR = 0.196, 95%CI = 0.076-0.511, P = .001) was a risk factor for MG. Male sex, post-operative complications, higher grade of MGFA classification, and thymoma Masaoka-Koga pathological stage were risk predictors for long-term prognosis of T-MG (P < .1). Use of preoperative anticholinesterase drugs (OR = 5.504, 95%CI = 1.424-21.284, P = .013) was identified as an independent predictor for T-MG., Conclusion: T-MG is clinically different from NT-MG, and thymoma is considered a risk factor for MG. Preoperative anticholinesterase drug use is a protective factor for long-term prognosis of T-MG. A comprehensive understanding of the characteristics of T-MG will likely help improve its prognosis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The primary and secondary aims were to investigate the prevalence of incidental mediastinal masses on low-dose chest CT examinations during health check-ups, and to review the radiological characteristics of prevascular mediastinal masses, respectively., Materials and Methods: This retrospective study included 38,861 participants (mean age: 57.1 years; range: 21-99 years; men: 51.3%; never-smokers: 57.4%) who underwent low-dose chest CT examinations between January 2011 and December 2016. All images with incidental mediastinal masses were reviewed, and prevascular mediastinal masses were assessed for qualitative and quantitative imaging characteristics by two radiologists. Univariate and multivariate analyses were performed in clinical and CT features between some combinations of participants., Results: Overall, 653 participants (1.68%, 653 of 38,861) had incidental mediastinal masses; 578 in prevascular mediastinum, including 93 intrathymic cysts and 24 thymic epithelial tumors. Presence of mediastinal mass was not significantly associated with sex (p = 0.089) and smoking history (p = 0.098) but with age (p < 0.001). Significant differences were found between intrathymic cysts and thymic epithelial tumors in terms of shapes (p = 0.049), contours (p = 0.018), and CT values (p = 0.012)., Conclusion: The prevalence of asymptomatic mediastinal masses on low-dose chest CT was 1.68%. CT values, shapes, and contours may effectively distinguish intrathymic cysts from thymic epithelial tumors.

Primary neuroendocrine tumors of the thymus are extremely rare. In patients with advanced disease, tumor growth control, and sometimes also syndrome control are the main goals of systemic therapy. Unfortunately, no standard therapies are available in clinical practice; therefore, clinical studies are strongly recommended. Axitinib (AXI) is a tyrosine kinase inhibitor, currently under investigation in an international phase II/III trial including thymic neuroendocrine tumors. Over the past 5 months, the entire world has been facing a devastating medical emergency brought about by a pandemic due to a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, in late 2019. Since then, health professionals have been expending all their efforts on trying to provide the best available treatments for patients involved. Patients with cancer, especially those with thoracic involvement, are at higher risk of coronavirus disease 19 (COVID-19) and its complications because of their immunosuppressive status caused by the cancer and the anticancer therapies. As it remains unclear how to optimally manage such patients, we wished to report our experience with a patient with a metastatic neuroendocrine tumor of the thymus infected with SARS-CoV-2 in the hope that it may provide some insights and reflections on the management of cancer patients during this challenging time in our history.

Background: Role of biomarkers for promotion of tumor proliferation (BPTPs) and for promotion of apoptosis (BPAs) in thymic malignant tumors is still unclear. The purpose of this study was to evaluate the relationship between BPTPs and/or BPAs and malignancy of thymic malignant tumors., Methods: Studies on thymic malignant tumors and biomarkers were searched in PubMed, ISI Web of Knowledge, and Embase databases, and all statistical analyses were conducted using Review Manager., Results: Twelve articles related to biomarkers and thymic malignant tumors were selected and analyzed. A relationship between BPAs and Masaoka stage was demonstrated for four markers, namely Bax, p73, Casp-9 and Bcl-2, included 138 stage I/II patients and 74 stage III/IV patients, and BPAs were significantly correlated with high Masaoka staging (P = 0.03). We further found a relationship between BPAs and degree of malignancy for four markers, namely Bax, p73, Casp-9 and Bcl-2, included 176 thymoma patients and 36 thymic carcinoma patients, and BPAs were significantly correlated with thymic carcinoma (P = 0.010). In addition, a relationship between BPTP and Masaoka staging was demonstrated for seven markers, namely Podoplanin, Glut-1, Muc-1, Egfr, Igf1r, c-Jun, and n-Ras, included 373 patients with stage I/II and 212 patients with stage III/IV, and BPTPs were significantly correlated with high Masaoka staging (P < 0.001). We also found a relationship between BPTPs and degree of malignancy for ten markers, namely Mesothelin, c-Kit (CD117), Egfr, Lat-1, Muc-1,Ema, Glut-1, Igf1r, c-Jun, and n-Ras, included 748 thymoma patients and 280 thymic carcinoma patients, and BPTPs were significantly correlated with thymic carcinoma (P < 0.001)., Conclusion: These findings show that high levels of BPTPs or BPAs are more closely related to thymic carcinoma and Masaoka stage III/IV, suggesting that BPTPs and BPAs may play an important role in the occurrence and development of thymic malignant tumors.

Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000-2014. Patients diagnosed in 1997-2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5-year relative survival (RS). During 2000-2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person-years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5-year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% [2002-2007] vs. 13.0% [2008-2013], p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020-2030 in Western countries., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objective: Although rare, thymic neuroendocrine tumors (TNET) and thymic carcinoma (TC) are the most common thymic nonthymomatous malignancies; their survival outcomes have not been thoroughly compared. We analyzed the clinical, treatment, and survival characteristics of TNET and TC., Methods: We retrospectively identified patients with a histologic diagnosis of TNET or TC in the National Cancer Database (2004 to 2015). Exclusion criteria were age <18 years and unstaged tumors. Descriptive statistics, survival analysis, and multivariable Cox regression analyses were used in elucidating associations., Results: One thousand four hundred eighty-nine patients were included (TNET: 19.8%). Patients with TNET were significantly younger (57 vs 62.5 years), more likely to be male (70.5% vs 60.0%), and have localized tumors (45.4% vs 32.3%). Patients with TC more frequently underwent chemotherapy (56.1% vs 34.9%), radiation (56.9% vs 39.3%), and trimodality therapy (21.3% vs 11.5%), while resection rates were similar (55.3% vs 58.3%). The 5-year survival was 62% for TNET and 52% for TC, but comparable following multivariable adjustment. Age, stage, and Charlson-Deyo score were negative predictors of survival, while surgery and trimodality therapy were positive predictors. On subanalysis, adjuvant radiation therapy (ART) improved the survival of margin-positive tumors and was an independent predictor of survival for both tumor types (hazard ratio = 0.5)., Conclusions: Our analysis of the largest series of TNET and TC showed a survival rate surpassing 50% at 5 years. These outcomes seem to be influenced by surgical resection and ART. Standardized staging and surgical protocols including lymph node sampling are still warranted to better elucidate the treatment algorithm of these tumors.

Background: To investigate the clinicopathologic characteristics and survival outcomes of patients with thymic epithelial tumors (TET) according to age at diagnosis., Results: A total of 4431 patients were analyzed. Gender, race, tumor histology and surgery were similar between different age groups. The 0-18 group was associated with a higher risk of distant metastasis. Compared to patients aged above 80, the hazard ratios (HR) for patients aged 0-18, 19-30, 31-40, 41-50, 51-60, 61-70, 71-80 were 1.079, 0.739, 0.614, 0.621, 0.633, 0.673, 0.861, respectively. From the subgroup analysis for the adult patients who were above 19 years old, we found that the 19-70 group had significant better cancer specific survival (CSS) and overall survival (OS) than the above 70 group., Conclusions: Age is a strong independent prognostic factor for survival in TET. Pediatric TET has a higher risk of distant metastasis and an inferior CSS. For the adults who were above 19, patients older than 70-year-old were associated with a shorter CSS., Methods: Information of 4431 TET patients was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic features, clinicopathologic characteristics and survival outcomes were compared between patients diagnosed at different age groups (0-18, 19-30, 31-40, 41-50, 51-60, 61-70, 71-80, above 80).

The ATM kinase is a master regulator of the DNA damage response to double-strand breaks (DSBs) and a well-established tumour suppressor whose loss is the cause of the neurodegenerative and cancer-prone syndrome Ataxia-Telangiectasia (A-T). A-T patients and Atm -/- mouse models are particularly predisposed to develop lymphoid cancers derived from deficient repair of RAG-induced DSBs during V(D)J recombination. Here, we unexpectedly find that specifically disturbing the repair of DSBs produced by DNA topoisomerase II (TOP2) by genetically removing the highly specialised repair enzyme TDP2 increases the incidence of thymic tumours in Atm -/- mice. Furthermore, we find that TOP2 strongly colocalizes with RAG, both genome-wide and at V(D)J recombination sites, resulting in an increased endogenous chromosomal fragility of these regions. Thus, our findings demonstrate a strong causal relationship between endogenous TOP2-induced DSBs and cancer development, confirming these lesions as major drivers of ATM-deficient lymphoid malignancies, and potentially other conditions and cancer types.

Management of myasthenia gravis (MG) in the presence of comorbidities may be difficult. We report the effect of comorbidities in the outcome of MG. The patients with MG during 1991-2016 were included and evaluated including their demographic variables, clinical findings, Myasthenia Gravis Foundation of America (MGFA) score. The patients were categorized into early onset (≤ 40 years) and late onset (> 40 years) MG. The comorbidities (autoimmune and miscellaneous) and iatrogenic complications were compared between early and late onset, and in good and poor outcome groups. Out of 81 patients with MG, 48 patients had early and 33 late onset. In 71 (88%) patients, comorbidities were present and were autoimmune in 8 (10%) and miscellaneous in all the patients (88%). Iatrogenic complications were present in 54 (67%) patients. Thymectomy was done in 19 patients; 16 had thymoma and 3 thymic hyperplasia. Myasthenic crisis occurred in 28 patients; 5 (18%) had autoimmune and all had miscellaneous comorbidities. The patients with poor outcome had ≥ 2 comorbidities, myasthenic crisis, leukocytosis, elevated serum bilirubin and creatinine, and increased number of hospital admissions (P < 0.05). Myasthenia gravis is associated with comorbidities in majority of patients especially in late onset group, and more than two comorbidities are related to poor outcome.

This study aimed to identify the trends in the incidence of thymic cancer, i.e., thymoma, thymic carcinoma, and thymic neuroendocrine tumor, in the United States. Data from the United States Cancer Statistics (USCS) database (2001-2015) and those from the Surveillance, Epidemiology, and End Results (SEER) database (SEER 9 [1973-2015], SEER 13 [1992-2015], and SEER 18 [2000-2015]) were used in this study. All incidences were per 100,000 population at risk. The trends in incidence were described as annual percent change (APC) using the Joinpoint regression program. Data from the USCS (2001-2015) database showed an increase in thymic cancer diagnosis with an APC of 4.89% from 2001 to 2006, which is mainly attributed to the significant increase in the incidence of thymoma and thymic carcinoma particularly in women. The incidence of thymic cancer did not increase from 2006 to 2015, which may be attributed to the increase in the diagnosis of thymic carcinoma from 2004 to 2015, with a concomitant decrease in thymoma from 2008 to 2015. Before declining, the age-specific incidence of thymic cancer peaked at ages 70-74 years, with a peak incidence at 1.06 per 100,000 population, and decreased in older age groups. The incidence of thymic cancer was higher in men than in women. Asian/Pacific Islanders had the highest incidence of thymoma, followed by black and then white people. The incidence of thymic carcinoma increased from 2004 to 2015, with a concomitant decrease in thymoma from 2008 to 2015. Asian/Pacific Islanders had the highest incidence of thymoma than other races., Competing Interests: The authors have declared that no competing interests exist.

Background: Thymic malignancies are rare and there are limited contemporary population-based epidemiological studies for this uncommon cancer., Patients and Methods: Adults aged 20 years and older diagnosed with thymic malignancies between 1988 and 2015 were identified from the California Cancer Registry (n = 1588). Trends in age-adjusted incidence rates were examined overall and according to race/ethnicity, and the proportion diagnosed according to stage was evaluated over time. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for overall survival (OS), and Fine and Gray competing risks regression for cause-specific survival (CSS)., Results: Age-adjusted incidence increased on average 2.08% per year over the study period (95% confidence interval [CI], 1.30%-2.86%; P < .0001), with an incidence of 0.277 cases per 100,000 in 2015. Incidence was highest among Asian/Pacific Islander and non-Hispanic black individuals. The proportion of unknown stage at diagnosis declined as localized diagnoses increased over time. Compared with patients with thymoma, those with thymic carcinoma had significantly worse OS (HR, 1.63; 95% CI, 1.33-2.01; P < .0001) and CSS (subdistribution HR, 2.99; 95% CI, 2.29-3.91; P < .0001). Advanced stage at diagnosis was also associated with worse survival. Surgical intervention was associated with better prognosis for patients with localized (HR, 0.08; 95% CI, 0.02-0.30; P = .0002) or regional disease (HR, 0.14; 95% CI, 0.06-0.34; P < .0001)., Conclusion: Thymic malignancy incidence is increasing in California. There was incidence variation across race/ethnicity, which warrants future study. These findings provide contemporary insight into the incidence and prognostic factors of thymic malignancies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Thymomas from 277 Fischer 344/N (F344/N), 10 Sprague Dawley (HSD:Sprague Dawley SD) (SD), 129 Wistar Han [Crl:WI(Han)] (WH), and 4 Wistar Outbred (WO) rats were reviewed from long-term studies in the National Toxicology Program (NTP) database. The incidence of thymomas in F344/N rats was slightly higher in males than in females, while the incidences in SD and WH rats were higher in females than in males. Only male WO rats were used in NTP studies. Of the 277 thymomas in F344/N rats, 235 (84.8%) were benign and 42 (15.2%) malignant, 14 of which exhibited metastasis. Of the 10 thymomas in SD rats, 5 (50%) were benign and 5 (50%) were malignant, one of which exhibited metastasis. Of the 129 thymomas in WH rats, 126 (98%) were benign and 3 (2%) were malignant, 1 with metastasis. Of the 4 thymomas in WO rats, 3 (75%) were benign and 1 (25%) was malignant, with no metastases. Malignant thymomas in F344/N and WH rats showed a propensity to be the cause of death and to result in early mortality, whereas the benign thymomas were associated less often with decreased survival. No occurrences of this neoplasm were reported to be related to exposure to any test articles.

Background & Objectives: Thymomas are rare, but most common anterior mediastinal lesions. The histomorphologic spectrum of thymic epithelial tumours (TETs) in Indian population has not been explored in depth. This study was aimed to assess the histomorphology of TETs in the Indian patients and correlate clinical parameters with pathological features., Methods: It was a retrospective study conducted in a tertiary referral hospital in north India. All morphologically confirmed cases of TETs since 2009 were included. Clinical details and histology slides were reviewed using the Modified Masaoka-Koga staging system and WHO 2015 classification. Clinicopathological correlation and survival analysis were done. A comparative review from other published Indian studies was performed., Results: A total of 219 cases of TETs (138 resections and 81 biopsies) were identified. The most common histomorphologic type was B2, and the most frequent stage was I. Types A/AB were common in older age (P<0.01). Clinically, higher stage tumours were found mostly in men (P<0.01), and these were Type B thymomas (P<0.01). Myasthenia gravis was more common in women (P<0.02) and in lower stages (P<0.05). Survival analysis revealed significant association between recurrence and tumour stage. Although thymic carcinoma was diagnosed on biopsy, no resectable case was identified., Interpretation & Conclusions: Our findings showed that the thymomas in Indian patients were most commonly Stage I tumours of B2 and AB histotypes. Resected thymic carcinomas were conspicuously absent in our study. More studies need to be done to establish the frequency and biology of TETs from India., Competing Interests: None

Introduction: Some myasthenia gravis (MG) patients are refractory to conventional treatments., Methods: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria., Results: Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10 -6 ). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003)., Discussion: HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188-191, 2019., (© 2019 Wiley Periodicals, Inc.)

Purpose: To compare the dose distributions produced in patients (pts) treated for thymic tumours with spot-scanning proton beam therapy (PBT) implemented with single-field uniform dose (SFUD), intensity-modulated radiation therapy (IMRT) and three-dimensional conformal photon-beam based radiotherapy (3D-CRT)., Methods: Twelve pts, treated with 3D-CRT, were included. Alternative IMRT and SFUD plans were constructed. The IMRT plans were created using a setup with beams incident from 5 to 6 different angles. For the SFUD plans, a field-specific planning target volume (PTV) was created for each patient and a clinical target volume (CTV)-based robust optimization was performed. A robustness evaluation was performed for the CTV for all SFUD plans. A dosimetric evaluation was conducted for the doses to the CTV and organs at risk (OARs) for all plans. The normal tissue complication probability (NTCP), for different endpoints, was calculated using the Lyman-Kutcher-Burman (LKB)-model and compared between plans., Results: SFUD was associated with significantly lower mean doses to the oesophagus, the heart, the left anterior descending coronary artery (LAD), lungs and breasts compared to 3D-CRT and IMRT. The maximum dose given to the spinal cord was significantly lower with SFUD. The risks for pneumonitis, esophagitis and myelopathy were significantly reduced in the SFUD plans., Conclusions: The present study showed dosimetric advantages of using scanned-beam PBT for the treatment of thymic tumours, as compared to 3D-CRT and IMRT, especially in regard to lower doses to the oesophagus and lungs. The risk of toxicity was reduced with SFUD., (Copyright © 2019. Published by Elsevier Ltd.)

Objectives: We queried the European Society of Thoracic Surgeons (ESTS) prospective thymic database for descriptive analysis and for comparison with the ESTS retrospective thymic database (1990-2010)., Methods: Data were retrieved (January 2007-November 2017) for 1122 patients from 75 ESTS institutions., Results: There were 484 (65%) thymomas, 207 (28%) thymic carcinomas and 49 (7%) neuroendocrine thymic tumours. Staging (Masaoka) included 483 (67%) stage I and II, 100 (14%) stage III and 70 (10%) stage IV tumours. The new International Association for the Study of Lung Cancer/International Thymic Malignancies Interest Group tumour, node and metastasis (TNM) classification was available for 224 patients and including 177 (85%) stage I-II, 37 (16%) stage IIIA and 10 (4%) stage IIIB tumours. Chemotherapy as induction and adjuvant treatment was used in 14% and 15% of the patients. Radiotherapy was almost exclusively used postoperatively (24%). A minimally invasive surgical approach (video-assisted thoracic surgery/robotic-assisted thoracic surgery) was used in 276 (33%) patients. The overall recurrence rate was 10.8% (N = 38). Compared to the ESTS retrospective database, the increased prevalence of thymic carcinomas (from 9% to 28%) and neuroendocrine thymic tumours (from 2% to 7%), an increase in the use of minimally invasive techniques (from 6% to 34%) and a wider use of chemotherapy as induction (from 9% to 15%) and adjuvant (from 2% to 16%) treatment were observed in the prospective database. The introduction of a set of variables considered essential for the data use ('minimum dataset') resulted in an increased average completeness rate., Conclusions: The reported data from the ESTS prospective thymic database confirm the recent trends in the management of thymic tumours. The ESTS prospective thymic database represents a powerful resource open to all ESTS members for the global effort to manage these rare tumours., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Bronchiectasis is a rare complication in patients with thymic neoplasm. The aim of this study was to investigate the clinical and radiological manifestations, laboratory tests, pathologic features, and outcome of treatment of bronchiectasis in patients with thymic neoplasm., Methods: From January 2000 to January 2018, 20 patients with a diagnosis of thymic neoplasm and bronchiectasis were hospitalized at the Peking Union Medical College Hospital. Clinical data was retrospectively analyzed., Results: The prevalence of bronchiectasis in thymic neoplasms in our cohort was 1.56% (20/1279). Eighteen patients were diagnosed with thymoma, while two patients were diagnosed with thymic carcinoid. The duration from diagnosis of thymic neoplasm to bronchiectasis varied. Distributions of bronchiectasis were bilateral in 17 patients and unilateral in three patients. Four patients were previously diagnosed with diffuse panbronchiolitis and another two were suspected with diffuse panbronchiolitis. Twelve patients had various parathymic syndromes, including Good syndrome, myasthenia gravis, and aplastic anemia. Thymectomy was performed in all of these patients. Macrolide antibiotics were administered to 10 patients, and the symptoms improved in 8., Conclusion: Bronchiectasis is a complication in thymic neoplasms, although prevalence is low. There may be multifactorial etiologies for bronchiectasis in patients with thymic neoplasms. Comprehensive treatment should be carried out to ensure optimal outcomes., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The relative prevalence of myasthenia gravis (MG) subtypes is changing, and their differential features and association with HLA class II alleles are not completely understood., Methods: Age at onset, presence/absence of autoantibodies (Ab) and thymoma were retrospectively considered in 230 adult Italian patients. Clinical severity, assessed by MGFA scale, and the highest Ab titer were recorded. Furthermore, we performed low/high resolution typing of HLA-DRB1 and HLA-DQB1 alleles to detect associations of these loci with MG subtypes., Results: There were two peaks of incidence: under 41 years of age, with female preponderance, and over 60 years, with higher male prevalence. The former group decreased and the latter increased significantly when comparing onset period 2008-2015 to 2000-2007. Thymomatous (TMG) patients showed a higher prevalence of severe phenotype and significantly higher anti-AChR Ab titer than non-thymomatous (NTMG) patients. Among the latter, those with onset after 60 years of age (LO-NTMG) displayed significantly higher Ab titers but lower MGFA grade compared to early-onset patients (< 41 years; EO-NTMG). Significant associations were found between HLA DQB1*05:01 and TMG patients and between DQB1*05:02 and DRB1*16 alleles and LO-NTMG with anti-AChR Ab., Conclusions: Two distinct cutoffs (< 41 and > 60 years) conveniently define EO-NTMG and LO-NTMG, with different characteristics. LO-NTMG is the most frequent disease subtype, with an increasing incidence. TMG patients reach higher clinical severity and higher antibody titers than NTMG patients. Moreover, TMG and LO-NTMG with anti-AChR Ab differ in their HLA-DQ association, providing further evidence that these two forms may have different etiologic mechanisms.

Background: The etiology of thymic epithelial tumors is unknown. Murine polyomavirus strain PTA has been shown to induce thymomas in mice. Recently, using diverse molecular techniques, we reported the presence of human polyomavirus 7 (HPyV7) in thymic epithelial tumors. In the present study, we investigated the prevalence of Merkel cell polyomavirus (MCPyV) in thymic epithelial tumors., Methods: Thirty-six thymomas were screened for MCPyV by PCR and subsequently tested by DNA and RNA in situ hybridization and immunohistochemistry. Twenty-six thymomas were diagnosed with myasthenia gravis (MG)., Results: MCPyV DNA was detected by PCR in 7 (19.4%) of the 36 thymic epithelial tumors and in six of these, the presence of MCPyV was confirmed by fluorescence situ hybridization. Of these, 3 (28.6%) revealed weak MCPyV LT-antigen protein expression. In addition, one of the MCPyV positive thymomas tested positive for MCPyV LT RNA with RNAscope. Of interest, two out of the three thymomas that previously tested positive for MCPyV by immunohistochemistry also tested positive for HPyV7. One of the 11 MG-negative and 2 of the 25 MG-positive were positive for MCPyV., Conclusions: MCPyV DNA and MCPyV protein expression can be detected in human epithelial thymoma; however, to a far lesser extent than HPyV7. Our data strongly indicate that because of its infrequent detection and weak expression, MCPyV is unlikely to play an important role in the etiopathogenesis of human thymomas., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objectives: The management of patients with locally advanced thymic malignancies remains controversial. Differing combinations of surgical resection, chemotherapy and radiation are used in the management of initial and relapsed disease. Treatment-related toxicities and quality of life could inform therapeutic options. This study describes health utility scores (HUS) in survivors with locally advanced thymic malignancies and investigates the impact of multimodality regimens on HUS., Methods: In a cross-sectional study (2014-2017), patients with Masaoka Stage II-IVa thymic malignancies completed various self-reported questionnaires, including EuroQol-5-Dimensions with visual analogue scale (VAS), Eastern Cooperative Oncology Group (ECOG) and Edmonton Symptom Assessment Scale tools. Trimodality versus uni- or bimodality regimens and aggressive versus non-aggressive management of recurrent disease were compared using regression analyses., Results: Of the 72 patients, 43 (60%) were male with a median age of 58 years, 65 (90%) had thymoma while 7 (10%) had thymic carcinomas; and median time since diagnosis was 50.5 months (range: 3-266). Median HUS and VAS did not differ between groups (trimodality n = 24 vs uni- or bimodality n = 48: HUS = 0.77 vs 0.80, P = 0.29; VAS = 80 vs 75, P = 0.79, respectively). The distributions of patient-reported ECOG were also similar (P = 0.86). Edmonton Symptom Assessment Scale scores for every assessed symptom were similar for different modalities of therapy. Median scores on these tools were also similar regardless of recurrence status or management of relapsed disease (aggressive versus non-aggressive)., Conclusion: Survivors with Stage II-IVa thymic malignancies report favourable HUS, VAS and self-reported ECOG with minimal symptom burden. These outcomes may be independent of number and type of initial treatment modalities or management of recurrence.

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The prognostic value of surgery and postoperative radiotherapy (PORT) for primary thymic neuroendocrine tumors (TNETs) was estimated using the SEER database., Methods: This retrospective study used SEER data of TNET patients between 1998 and 2015. Propensity score matching (PSM) was performed according to whether surgery was performed. The prognostic effects on overall survival (OS) and cancer-specific survival (CSS) were evaluated using multivariate Cox regression., Results: A total of 3947 patients were included: 293 (7.4%) TNET, 2788 (70.6%) thymoma, and 866 (21.9%) thymic carcinoma. Compared to other subtypes, TNET patients were younger, included a larger proportion of men, had a well or moderately differentiated histological grade, higher disease stage at diagnosis, and were more likely to have regional lymph node metastasis. The median OS and CSS for TNET were 82.9 (95% confidence interval 74.3-91.4) and 101.9 (95% confidence interval 91.9-111.8) months, respectively, significantly shorter than for thymomas. In the matched cohort of TNET patients, multivariate analysis of OS and CSS revealed a significantly poorer prognosis in the non-surgery group (P < 0.001). Compared to total/radical resection, TNET patients who underwent debulking resection had significantly inferior outcomes (P < 0.05). Postoperative radiotherapy favorably impacted OS and CSS in Masaoka-Koga stage III-IV TNET patients; this OS impact was also observed in stage IIB patients., Conclusion: TNETs are extremely rare with relatively dismal outcomes. This analysis revealed the role of complete surgical resection and the favorable effect of postoperative radiotherapy in specific TNET subgroups., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objective: To provide an estimated prevalence and describe the clinical features of myasthenia gravis (MG) in Chile., Method: We carried out (i) a prevalence study of MG using the capture-recapture method and the hospital register of pyridostigmine prescription in South-East Santiago (ii) a nationwide survey of MG patients., Results: Prevalence in adults in South-East Santiago was estimated to be 8.36/100 000 inhabitants (CI: 95%, 7.98-8.80). From the nationwide survey, 405 questionnaires were analysed, there was a female/male ratio of 2.2:1. The mean age of onset of symptoms was 38.7 years (range 1-89). The onset was ocular in 46.4%, oculobulbar in 11.6%, bulbar in 8.9%, limbs in 11.6% and generalized in 21.4%. Of the 13.3% of patients who had had a diagnosis of thymoma, only four of these patients were >60 years old at onset. Thymomas were commoner in patients living in mining counties. Patients ≥60 years old at onset of MG formed 19.5% of the sample, female/male ratio 0.97:1. Associated autoimmune diseases were reported in 14% of patients and in family members of 31.8% of patients. A total of 78 patients had to change work due to MG and 68 needed help in carrying out daily activities., Conclusions: This study reduces the gap in information about MG in South America. The prevalence of MG in Chile is within the range described worldwide. We did not see an increase in male frequency in the older age of onset group and thymoma was more frequent in the fifth and sixth decades., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To study the incidence and pattern of lymph node metastases in thymic malignancies., Methods: This multicenter prospective observational trial with intentional lymph node dissection was carried out by the Chinese Alliance for Research in Thymomas (ChART). Data on patients with thymic tumors without pretreatment were collected prospectively. Results from this prospective study were then compared with those from a previously reported ChART retrospective study., Results: Among 275 patients, metastasis was detected in 41 nodes (3.04%) in 15 patients (5.5%). The rate of lymph node metastasis was 2.1% (5/238) in patients with thymomas, 25% (6/24) in those with thymic carcinomas, and 50% (4/8) in those with neuroendocrine tumors (P < .001). The rate of lymph node metastasis in category T1 to T4 tumors was 2.7% (6/222) in T1, 7.7% (1/13) in T2, 18.4% (7/38) in T3, and 50% (1/2) in T4 (P < .001). Nodal involvement was significantly higher compared with the ChART retrospective study (5.5% vs 2.2%; P = .002), although the 2 groups were comparable in terms of tumor stage and histology. Metastasis was found in N1 nodes in 13 patients (86.7%) and in N2 nodes in 8 patients (53.3%); 6 patients (40%) had simultaneous N1/N2 diseases and 6 (40%) had multistation involvement. Based on World Health Organization histological classification and Union for International Cancer Control T category, patients were divided into a low-risk group (1/192; 0.5%) with T1-2 and type A-B2 diseases and a high-risk group (14/83; 16.9%) of category T3 and above or histology B3 and above tumors for nodal metastasis (P < .001). On multivariate analysis, type B3/thymic carcinoma/neuroendocrine tumors, category T3 or above, and N2 dissection predicted a greater likelihood of finding nodal metastasis., Conclusions: Lymph node involvement in thymic malignancies is more common than previously recognized, especially in tumors with aggressive histology and advanced T category. Intentional lymph node dissection increases the detection of nodal involvement and improves accuracy of staging. In selected high-risk patients, systemic dissection of both N1and N2 nodes should be considered for accurate tumor staging., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Thymic epithelial tumors (TET) are the most common tumors of the anterior mediastinum. Patients with advanced/metastatic disease are usually treated with palliative chemotherapy (CT). Unfortunately, even though various palliative CT regimens have been used for long time, there is a real scarcity of published Indian data regarding the experience of palliative CT in metastatic TET (mTET)., Materials and Methods: This is a retrospective analysis of mTET patients treated between January 2010 and September 2017. Patients who received at least three cycles of first-line palliative CT were included for analysis of response rates, toxicity, and survival and prognostic factors., Results: Of the 49 mTET patients, 27 (55.1%) were males. The median age at diagnosis was 52 years (range: 25-65). Eighteen patients (36.7%) had Masaoka Stage IVa disease, and the rest of the patients had IVb disease. The most common site of metastasis was pleuropericardium (n = 18), followed by lungs (n = 16) and lymph nodes (n = 9). The median progression-free survival and overall survival (OS) were 11.2 months (95% confidence interval [CI], 8.7-13.6) and 20.2 months (95% CI, 17.1-22.8), respectively, for the whole cohort (n = 49). The median OS of patients with Stage IVa disease was significantly better than that of the patients with Stage IVb disease (log-rank P = 0.000). Moreover, the "responders" to first-line CT had a significantly better median OS than the "nonresponders" (log-rank P = 0.000). Various first-line palliative CT regimens were well tolerated in our patients., Conclusion: Adriamycin Cisplatin Vincristine Cyclophosphamide (ADOC), Cyclophosphamide Adriamycin Cisplatin, and paclitaxel + carboplatin all are viable first-line palliative CT options for mTET and showed a comparable survival in Indian patients. The present study suggested that "responders" to first-line CT and those with Stage IVa disease might have a better survival than "nonresponders" and those with Stage IVb disease, respectively., Competing Interests: None

The incidence of thymic epithelial tumors (TETs) in the Chinese population was much higher than that in the North American population. In clinical treatment, the prognosis of benign tumors after surgical resection was significantly better than that of malignant tumors. Currently, the commonly used clinical indicators for TET staging included Masaoka staging and WHO (2015) pathological criteria; however, the distinction between the benign and malignant tumors and diagnosis is yet to be explored. The current study demonstrated that the expression of PD-L1 in tumor cells was correlated with the degree of TET malignancy. The quantitative analysis of PD-L1 expression in 70 cases of TET tumor samples revealed that the positive rate of PD-L1 expression in types A, AB, B1, and B2 of thymoma (40 cases) was 37.5% (15/40), which was significantly lower than that in type B3 thymoma and thymic carcinoma (76.67%, 30 cases, 23/30) as demonstrated by chi-square test ( P < 0.05). In addition, the two methods were analyzed for the quantitative detection of PD-L1 expression. The results from the estimation of transcriptional RNA expression and quantitative protein immunohistochemistry were consistent ( r = 0.745). Furthermore, we also analyzed PD-L1 expression level in different types of TETs from TCGA database and observed that higher PD-L1 expression was in thymic carcinoma than in thymoma. Therefore, it could be concluded that PD-L1 expression in TET cells was correlated with the degree of malignancy, whereas the estimation of PD-L1 expression was potentially applicable in the clinical staging of TETs.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.