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Neurology(R) Neuroimmunology &... Mar 2023Myasthenia gravis (MG) is an autoimmune disease associated with comorbid thymoma in 10%-15% of cases. Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) expressed by T...
BACKGROUND AND OBJECTIVES
Myasthenia gravis (MG) is an autoimmune disease associated with comorbid thymoma in 10%-15% of cases. Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) expressed by T cells downregulates T-cell-mediated immune response. Polymorphisms in the CTLA4 gene have been associated with the development of MG. In this context, we aimed to determine whether CTLA4 expression in the thymoma differs between patients with and without MG and whether CTLA4 gene polymorphisms are associated with these differences.
METHODS
This is a retrospective study of all patients, with and without MG, surgically treated at our institution for thymoma between January 2010 and December 2020. Ten samples were obtained from normal thymuses as controls. The number of CTLA4-positive cells in paraffin-embedded thymoma samples was determined by immunohistochemistry. The presence of follicular-center and regulatory T-cell lymphocytes was determined by immunohistochemistry (B-cell lymphoma [BCL]-6 expression) and double immunofluorescence-based staining of CD4-FOXP3, respectively. We evaluated the association between thymic expression of CTLA4 and the development of MG. We also determined the association between CTLA4 expression and various clinical and prognostic characteristics of MG. We sequenced the CTLA4 gene and evaluated possible associations between CTLA4 polymorphisms and thymic CTLA4 expression. Finally, we assessed the potential association between these polymorphisms and the risk of MG.
RESULTS
Forty-one patients with thymoma were included. Of them, 23 had comorbid MG (56.1%). On average, patients with MG had fewer CTLA4-positive cells in the thymoma than non-MG patients: 69.3 cells/mm (95% CIs: 39.6-99.1) vs 674.4 (276.0-1,024.0) cells/mm; = 0.001 and vs controls (200.74 [57.9-343.6] cells/mm; = 0.02). No between-group differences (MG vs non-MG) were observed in the number of cells positive for BCL6 or CD4-FOXP3. CTLA4 expression was not associated with differences in MG outcome or treatment refractoriness. Two polymorphisms were detected in the CTLA4 gene, rs231770 (n = 30 patients) and rs231775 (n = 17). MG was present in a similar proportion of patients for all genotypes. However, a nonsignificant trend toward a lower CTLA4-positive cell count was observed among carriers of the rs231775 polymorphism vs noncarriers: 77.9 cells/mm (95% CI: -51.5 to 207.5) vs 343.3 cells/mm (95% CI: 126.2-560.4).
DISCUSSION
Reduced CTLA4 expression in thymoma may predispose to a higher risk of developing MG.
Topics: Humans; Thymoma; CTLA-4 Antigen; Retrospective Studies; Thymus Neoplasms; Myasthenia Gravis; Forkhead Transcription Factors; Probability
PubMed: 36697230
DOI: 10.1212/NXI.0000000000200085 -
Tidsskrift For Den Norske Laegeforening... Jun 2023Metastatic thymoma is a rare and serious condition that is treated with cytostatics according to the guidelines. Cytostatics have limited efficacy and are toxic. This...
Metastatic thymoma is a rare and serious condition that is treated with cytostatics according to the guidelines. Cytostatics have limited efficacy and are toxic. This case report illustrates how glucocorticoid treatment can have a significant effect.
Topics: Humans; Thymoma; Cytostatic Agents; Glucocorticoids; Thymus Neoplasms
PubMed: 37341399
DOI: 10.4045/tidsskr.22.0670 -
BMC Neurology Apr 2024Non-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.
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.
Topics: Humans; Myasthenia Gravis; Alopecia; Female; Male; Taste Disorders; Middle Aged; Adult; Aged; Japan; Registries; Thymoma; Incidence
PubMed: 38664714
DOI: 10.1186/s12883-024-03644-w -
Frontiers in Immunology 2022Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine... (Review)
Review
Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.
Topics: Epithelial Cells; Humans; Neoplasms, Glandular and Epithelial; RNA, Long Noncoding; Thymoma; Thymus Neoplasms
PubMed: 35529877
DOI: 10.3389/fimmu.2022.867181 -
Orphanet Journal of Rare Diseases Aug 2022Several retrospective studies have identified risk factors associated with ocular myasthenia gravis (OMG) generalization in non-surgical patients. However, the outcomes...
BACKGROUND
Several retrospective studies have identified risk factors associated with ocular myasthenia gravis (OMG) generalization in non-surgical patients. However, the outcomes of OMG after thymectomy have not been investigated fully. This study aimed to explore the clinical predictors of post-thymectomy OMG prognosis.
METHODS
We performed a retrospective review of OMG patients who underwent thymectomy at our institution from January 2012 to December 2021. Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate associations between clinical features and prognosis. The main outcome measures were OMG conversion, complete stable remission (CSR), and clinical improvement.
RESULTS
Fifty-eight patients were identified for conversion analysis. Thirteen (22.4%) developed generalized myasthenia gravis (GMG) at a median time of 12.7 (3-37.3) months from symptom onset. Repetitive nerve stimulation (RNS)-positivity was associated with increased risk of conversion to GMG (P = 0.002). Patients with histotype B2/B3 thymoma showed a higher risk of conversion (P = 0.002) than did patients with hyperplasia and AB/B1 thymoma. Fifty-two patients fulfilled the criteria for CSR and improvement. Sixteen (30.8%) achieved CSR at a median time of 28.7 (15-54) months after thymectomy. Fifteen (28.8%) showed clinical improvement at last follow up. Patients who achieved CSR showed a younger age of onset (P = 0.022), lower percentage of acetylcholine receptor antibody-seropositivity (P = 0.029). Histologically, patients with thymic hyperplasia and stage I thymoma showed a higher chance of CSR (P = 0.010) than did patients with stage II/III thymoma. Multivariate analysis revealed that RNS-positivity (hazard ratio [HR] 6.007, P = 0.021) and histotype B2/B3 thymoma (HR 4.611, P = 0.048) were associated with OMG conversion. Thymic hyperplasia and stage I thymoma (HR 0.300, P = 0.026) were associated with OMG CSR after thymectomy.
CONCLUSION
For OMG patients after thymectomy, RNS-positivity and histotype B2/B3 thymoma are independent predictors of conversion to GMG. On the other hand, thymic hyperplasia and stage I thymoma independently predict CSR.
Topics: Humans; Myasthenia Gravis; Prognosis; Retrospective Studies; Risk Factors; Thymectomy; Thymoma; Thymus Hyperplasia; Thymus Neoplasms; Treatment Outcome
PubMed: 35945595
DOI: 10.1186/s13023-022-02454-y -
Journal of Cardiothoracic Surgery Apr 2023The aim of this bibliometric analysis was twofold: to identify the 100 most cited research articles on thymoma and to highlight future research opportunities in light of...
OBJECTIVES
The aim of this bibliometric analysis was twofold: to identify the 100 most cited research articles on thymoma and to highlight future research opportunities in light of past and current research efforts.
METHODS
The Web of Science database was queried to identify the 100 most cited articles on thymoma. Imformations relevant to scientific research were extracted and analyzed: first author, journal, impact factor, type of article, year of publication, country, organization and keywords.
RESULTS
The publication year of the top 100 most cited articles ranged from 1981 to 2018, and the number of citations ranged from 97 to 1182. Most of the included articles are original (75/100) and are mainly retrospective studies (52/75). The United States has the most published articles and citations, and the Annals of Thoracic Surgery is the most sourced journal (n = 16). Through VOSviewer analysis, high-density keywords mainly come from thymic carcinoma/invasive thymoma management, immune-related diseases, and laboratory research.
CONCLUSIONS
To our knowledge, this is the first bibliometric study on thymoma. We found most of the top 100 most cited articles are original and retrospective research. The United States has the published and cited works. Presently, the hot keywords for thymoma research has gradually tilted towards immune-related diseases and laboratory research.
Topics: Humans; United States; Thymoma; Retrospective Studies; Bibliometrics; Thymus Neoplasms
PubMed: 37029418
DOI: 10.1186/s13019-023-02201-9 -
Oncology Reports Jun 2021Due to the lack of specific symptoms in early thymic epithelial tumours (TETs), patients are mostly in the advanced stage at the time of presentation. The aim of the...
Due to the lack of specific symptoms in early thymic epithelial tumours (TETs), patients are mostly in the advanced stage at the time of presentation. The aim of the present study was to explore the mechanism by which the long noncoding RNA (lncRNA) LOXL1‑AS1 affects thymoma and thymic carcinoma progression by targeting the miR‑525‑5p‑ axis. Bioinformatics was used to analyse the process of LOXL1‑AS1 targeting miR‑525‑5p‑ and its expression characteristics in TET. The relationships between LOXL1‑AS1, miR‑525‑5p, and prognosis were analysed. The dual luciferase reporter assay was applied to verify targeting. The gene was knocked down or overexpressed by plasmid transfection. Cell counting kit 8 (CCK‑8) assay, flow cytometry and Transwell assay were used to detect cell viability, apoptosis and invasion ability, respectively. Proteins and RNAs were examined by western blot analysis and qPCR, respectively. A tumour‑burdened assay was used to perform verification. LOXL1‑AS1 and were overexpressed in thymoma and thymic carcinoma; high levels of LOXL1‑AS1 and were associated with poor prognosis, and there was a significant positive correlation between their levels. Downregulation of miR‑525‑5p expression was also associated with poor prognosis of patients. Clinical trials also demonstrated the same trends. miR‑525‑5p inhibited the expression of protein by targeting the 3'‑untranslated region (UTR) of mRNA. LOXL1‑AS1 promoted the expression of as a sponge targeting miR‑525‑5p. Animal experiment results also showed that knockdown of miR‑525‑5p promoted cancer by promoting the expression of . In conclusion, LOXL1‑AS1 and are highly expressed in thymoma and thymic carcinoma; miR‑525‑5p is expressed at low levels in thymoma and thymic carcinoma; and downregulation of miR‑525‑5p is associated with poor prognosis. In summary, this study demonstrates that LOXL1‑AS1 acts as a sponge that targets miR‑525‑5p to promote expression, thereby promoting the growth and invasion and inhibiting apoptosis of thymoma and thymic carcinoma cells.
Topics: 3' Untranslated Regions; Animals; Apoptosis; Cell Line, Tumor; Computational Biology; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; HSP70 Heat-Shock Proteins; Humans; Mice; MicroRNAs; Mitochondrial Proteins; Neoplasm Invasiveness; Prognosis; RNA, Long Noncoding; Survival Rate; Thymectomy; Thymoma; Thymus Gland; Thymus Neoplasms; Xenograft Model Antitumor Assays
PubMed: 33907842
DOI: 10.3892/or.2021.8068 -
JCO Precision Oncology Feb 2023Despite favorable clinical outcomes, a subset of patients with thymic epithelial tumors (TETs) develop metastasis. The Cancer Genome Atlas (TCGA) provides genomic data...
BACKGROUND
Despite favorable clinical outcomes, a subset of patients with thymic epithelial tumors (TETs) develop metastasis. The Cancer Genome Atlas (TCGA) provides genomic data on primary TETs (pTETs). This study assessed the molecular alterations and uncovered targetable pathways in metastatic TETs (mTETs).
METHODS
From 2015 to 2020, 49 patients with stage IV TETs underwent Clinical Laboratory Improvement Amendments-based sequencing using whole-exome sequencing (n = 33), panel-based testing (n = 12), and/or liquid biopsy (n = 24). Specimens were obtained from a metastatic organ (n = 36) or relapsed primary mediastinal mass (n = 10), whereas four patients underwent a liquid biopsy only. Data on pTETs were derived from the TCGA.
RESULTS
Compared with the pTET data set, patients with mTETs were younger (54 years 60.5 years, = .009) and had more aggressive histologies, with the most common tumor type being thymic carcinoma (n = 22, 40.7%) and B3 thymoma (n = 15, 27.8%). GTF2I was the most altered gene in primary thymomas (48.80%, n = 60). In metastatic thymoma and thymic carcinoma, TP53 was the most common genetic alteration (31% and 36%, respectively). In mTETs, the genomic alteration occurred in the TP53/CDK, EGFR/RAS, and PI3K/mTOR pathways. Biopsies obtained from distant metastasis were more commonly found to contain targetable mutations. There was an overlap of 61% (22 of 36) between tissue and liquid biopsy genomic alterations.
CONCLUSION
Clinically actionable genomic alterations are frequently observed in mTETs, indicating a value of repeat biopsy (preferably from a metastatic site of TETs for sequencing at the time of recurrence (TCGA data).
Topics: Humans; Thymoma; Thymus Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial
PubMed: 36787505
DOI: 10.1200/PO.22.00465 -
Scientific Reports Mar 2023In recent years, thoracoscopic and robotic surgical procedures have increasingly replaced median sternotomy for thymoma and thymic carcinoma. In cases of partial...
In recent years, thoracoscopic and robotic surgical procedures have increasingly replaced median sternotomy for thymoma and thymic carcinoma. In cases of partial thymectomy, the prognosis is greatly improved by ensuring a sufficient margin from the tumor, and therefore intraoperative fluorescent imaging of the tumor is especially valuable in thoracoscopic and robotic surgery, where tactile information is not available. γ-Glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) has been applied for fluorescence imaging of some types of tumors in the resected tissues, and here we aimed to examine its validity for the imaging of thymoma and thymic carcinoma. 22 patients with thymoma or thymic carcinoma who underwent surgery between February 2013 and January 2021 were included in the study. Ex vivo imaging of specimens was performed, and the sensitivity and specificity of gGlu-HMRG were 77.3% and 100%, respectively. Immunohistochemistry (IHC) staining was performed to confirm expression of gGlu-HMRG's target enzyme, γ-glutamyltranspeptidase (GGT). IHC revealed high GGT expression in thymoma and thymic carcinoma in contrast to absent or low expression in normal thymic parenchyma and fat tissue. These results suggest the utility of gGlu-HMRG as a fluorescence probe for intraoperative visualization of thymomas and thymic carcinomas.
Topics: Humans; Thymoma; Thymus Neoplasms; gamma-Glutamyltransferase; Optical Imaging; Fluorescent Dyes
PubMed: 36882498
DOI: 10.1038/s41598-023-30753-2 -
Radiology and Oncology Mar 2023Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease's next-generation sequencing (NGS) genomic profiling.
MATERIALS AND METHODS
We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12 December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria.
RESULTS
Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, , , and , emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes (OR = 1.58, CI [1.51, 1.66] p < 0.00001) (OR = 1.36, CI [1.12, 1.65], p < 0.002), and (OR = 1.02, CI [1.00, 1.04], p < 0.001).
CONCLUSIONS
According to obtained data, we noticed that the gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested , and genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma.
Topics: Humans; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; High-Throughput Nucleotide Sequencing; Transcription Factors, TFIII
PubMed: 36942904
DOI: 10.2478/raon-2023-0013