Constitutional Factors and Irradiation as Risk Factors for Thymoma: A European Case-Control Study.

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.

The contribution of rural/urban residence to incidence and survival in thymoma and thymic carcinoma, a retrospective cohort study of the SEER 2000-2020 database.

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.

Taste disorders and alopecia in myasthenia gravis.

BACKGROUND: Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. METHODS: We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. RESULTS: Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. CONCLUSION: Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.

Attitudes and Beliefs Toward Thymectomy in the Myasthenia Gravis Patient Registry.

OBJECTIVES: To evaluate patient attitudes and beliefs toward thymectomy for myasthenia gravis (MG). METHODS: The Myasthenia Gravis Foundation of America administered a questionnaire to the MG Patient Registry, an ongoing longitudinal survey of adult MG patients. Questions assessed reasons for or against thymectomy and how hypothetical scenarios would have affected their decision. RESULTS: Of 621 respondents, 190 (31%) reported a history of thymectomy. Of those who underwent thymectomy for nonthymomatous MG, 97 (51.6%) ranked symptom improvement as most important and 100 (53.2%) ranked reducing medication as least important. Among 431 nonthymectomy patients, the most frequent reason for not undergoing thymectomy was that their doctor did not discuss it (152 of 431 = 35.2%) and 235 (56.8%) said that they would have considered it more strongly if their doctor spent more time discussing it. CONCLUSIONS: Thymectomies are motivated more by symptoms than by medication, and a lack of neurologist discussion is the most common barrier to thymectomy.

Nomogram predicts the prognosis of patients with thymic carcinoma: A population-based study using SEER data.

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.

Five Times Reactivation of COVID-19 in a Patient with Thymoma.

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.

Trends in Incidence and Survival of Patients With Thymic Epithelial Tumor in a High-Incidence Asian Country: Analysis of the Korean Central Cancer Registry 1999 to 2017.

INTRODUCTION: To report the trends in incidence and survival associated with thymic epithelial tumors (TETs) in Korea. METHODS: Data from 1999 to 2017 were obtained from the Korean Central Cancer Registry. Age-standardized incidence rates and average annual percentage changes (AAPCs) were calculated. Net survival (NS) was estimated by the Pohar-Perme method. RESULTS: Among 5812 patients diagnosed with having TETs, 58.9%, 38.1%, and 3.0% were diagnosed with having thymoma, thymic carcinoma, and thymic neuroendocrine tumor (NET), respectively. Age-standardized incidence rates were 0.50, 0.30, 0.18, and 0.02 per 100,000 for all TETs and the respective subtypes. There was an increase in incidence of all TETs (AAPC = 6.1%) and subtypes: thymoma (AAPC = 5.6%), thymic carcinoma (AAPC = 7.0%), and thymic NET (AAPC = 3.4%). Proportions of patients with thymoma, thymic carcinoma, and thymic NET were 58.9%, 38.1%, and 3.0%, respectively. For thymoma, the relative proportion of distant stage decreased (19.4% in 2005 to 8.8% in 2017) and low-grade WHO subtype (A, AB, B1) increased faster than high-grade WHO type (B2, B3) (AAPC = 19.8% versus 9.6%). For thymoma, the 5-year NS was 82.3%. This increased from 64.3% in 1999 to 2002 to 90.6% in 2013 to 2017. For thymic carcinoma, the 5-year NS was 46.2% and only slightly increased from 39.4% in 1999 to 2002 to 47.9% in 2013 to 2017. CONCLUSIONS: This study indicates a high incidence of TET and its continuous increase in Korea. The proportion of thymic carcinoma was relatively higher than in the United States or Europe. Survival for thymoma improved during the study period, whereas this was not evident for thymic carcinoma or thymic NET.

Multi-institutional survey of thymic carcinoma patients in Hokushin region.

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.

Characteristics of myasthenia gravis in elderly patients: a retrospective study.

BACKGROUND: The incidence of myasthenia gravis (MG) is increasing, and its characteristics in elderly patients are believed to differ from those in younger patients. However, only a few studies have focused on elderly patients with MG. OBJECTIVE: To review the characteristics of MG in elderly patients and evaluate whether older age is an independent factor associated with achieving minimal manifestation status (MMS). METHODS: This retrospective cohort study included 367 patients (319 non-elderly and 48 elderly patients) with MG enrolled at Xiangya Hospital from September 1, 2016, to December 31, 2018. We collected demographic data and information regarding comorbidities, antibody status, Myasthenia Gravis Foundation of America classification, affected muscle groups, thymoma, and treatment. MMS was defined as the primary outcome. RESULTS: Comorbidities were more common in elderly than in younger patients with MG. Anti-acetylcholine receptor antibody was the dominant subtype, whereas anti-muscle-specific tyrosine kinase antibody was rare and detected only in non-elderly patients. Elderly patients were more likely than younger patients to have generalized MG, but the frequency of thymoma was lower (28.5% vs. 10.4%, p = 0.0078). MMS or better was achieved in 154 (48.3%) and 13 (27.1%) non-elderly and elderly patients, respectively. Older age did not appear to be an independent factor associated with MMS (hazard ratio = 0.625; 95% confidence interval, 0.345-1.131). CONCLUSIONS: Older age was not an independent factor for a worse prognosis in patients with MG. The treatment of elderly patients with MG should be individually tailored.

Two types of immune infiltrating cells and six hub genes can predict the occurrence of myasthenia gravis in patients with thymoma.

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.

GTF2I Mutation in Thymomas: Independence From Racial-Ethnic Backgrounds. An Indian/German Comparative Study.

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.

Thymoma and Autoimmune Encephalitis: Clinical Manifestations and Antibodies.

OBJECTIVE: To report the clinical, neuroimaging, and antibody associations in patients with autoimmune encephalitis (AE) and thymoma. METHODS: A retrospective cohort study of 43 patients was conducted. Antibody determination and immunoprecipitation to characterize novel antigens were performed using reported techniques. RESULTS: Patients' median age was 52 years (range: 23-88 years). Forty (93%) had neuronal surface antibodies: gamma-aminobutyric acid receptor A (GABAAR) (15), amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) (13), contactin-associated protein-like 2 (CASPR2) (4), leucine-rich, glioma inactivated 1 (LGI1) (3), glycine receptor (GlyR) (3), and unknown antigens (2). Concurrent antibodies against intracellular antigens occurred in 13 (30%; 9 anti-collapsin response mediator protein 5 [CRMP5]) and were more frequent in anti-AMPAR encephalitis (54% vs 20%; p = 0.037). The most common clinical presentation was encephalitis with multiple T2/fluid-attenuated inversion recovery hyperintense lesions in 23 (53%) patients (15 GABAAR, 5 AMPAR, and 1 unknown neuropil antibody), followed by encephalitis with peripheral nerve hyperexcitability in 7 (16%; 4 CASPR2, 2 LGI1, and 1 unknown antibody), limbic encephalitis in 6 (14%; 4 AMPAR, 1 LGI1, and 1 antibody negative), progressive encephalomyelitis with rigidity and myoclonus in 4 (9%; 3 GlyR and 1 AMPAR antibodies), and encephalitis with normal MRI in 3 (7%; AMPAR antibodies). Anti-GABAAR encephalitis was more prevalent in Japanese patients compared with Caucasians and other ethnicities (61% vs 16%; p = 0.003). In anti-AMPAR encephalitis, 3/4 patients with poor and 0/6 with good outcome had concurrent CRMP5 antibodies (p = 0.033). Immunoprecipitation studies identified metabotropic glutamate receptor 3 antibodies that were additionally found in 5 patients (3 with and 2 without encephalitis). CONCLUSIONS: AE in patients with thymoma include several clinical-radiologic syndromes that vary according to the associated antibodies. Anti-GABAAR encephalitis was the most frequent AE and occurred more frequently in Japanese patients.

Lymph Node Dissection in Thymoma: Is it worth it?

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.

Characteristics and outcomes of thymomas in Latin America: Results from over 10 years of experience (CLICaP-LATimus).

BACKGROUND: Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. METHODS: This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. RESULTS: A total of 135 patients were included. Median age at diagnosis was 53 years old (19-84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0-1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka-Koga system, overall survival (OS) at five-years was 73.4%, 63.8% and 51%, at stages I-II, III-IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1-7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3-12.7]; p = 0.016) were significantly associated with increased risk of death. CONCLUSIONS: Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control.

Clinical characteristics and outcomes of thymoma-associated myasthenia gravis.

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.

Subclinical myasthenia gravis in thymomas.

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.

Thymomatous myasthenia gravis: 10-year experience of a single center.

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.

Clinical features and prognostic impact of coexisting autoimmune disease other than myasthenia gravis in resected thymomas: analysis of a Japanese multi-institutional retrospective database.

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 Duke myasthenia gravis clinic registry: I. Description and demographics.

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.

Thymic Neuroendocrine Tumors and Thymic Carcinoma: Demographics, Treatment, and Survival.

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.