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Journal of Thoracic Oncology : Official... Dec 2022The pathogenesis of thymic epithelial tumors remains largely unknown. We previously identified GTF2I L424H as the most frequently recurrent mutation in thymic epithelial...
INTRODUCTION
The pathogenesis of thymic epithelial tumors remains largely unknown. We previously identified GTF2I L424H as the most frequently recurrent mutation in thymic epithelial tumors. Nevertheless, the precise role of this mutation in tumorigenesis of thymic epithelial cells is unclear.
METHODS
To investigate the role of GTF2I L424H mutation in thymic epithelial cells in vivo, we generated and characterized a mouse model in which the Gtf2i L424H mutation was conditionally knocked-in in the Foxn1+ thymic epithelial cells. Digital spatial profiling was performed on thymomas and normal thymic tissues with GeoMx-mouse whole transcriptome atlas. Immunohistochemistry staining was performed using both mouse tissues and human thymic epithelial tumors.
RESULTS
We observed that the Gtf2i mutation impairs development of the thymic medulla and maturation of medullary thymic epithelial cells in young mice and causes tumor formation in the thymus of aged mice. Cell cycle-related pathways, such as E2F targets and MYC targets, are enriched in the tumor epithelial cells. Results of gene set variation assay analysis revealed that gene signatures of cortical thymic epithelial cells and thymic epithelial progenitor cells are also enriched in the thymomas of the knock-in mice, which mirrors the human counterparts in The Cancer Genome Atlas database. Immunohistochemistry results revealed similar expression pattern of epithelial cell markers between mouse and human thymomas.
CONCLUSIONS
We have developed and characterized a novel thymoma mouse model. This study improves knowledge of the molecular drivers in thymic epithelial cells and provides a tool for further study of the biology of thymic epithelial tumors and for development of novel therapies.
Topics: Animals; Humans; Mice; Mutation; Neoplasms, Glandular and Epithelial; Thymoma; Thymus Neoplasms; Transcription Factors, TFII; Transcription Factors, TFIII
PubMed: 36049655
DOI: 10.1016/j.jtho.2022.08.008 -
Journal of Thoracic Oncology : Official... Oct 2010Thymomas are the most frequently encountered tumors of the mediastinum and often present with either localized or locally advanced disease. The prognosis in thymoma has... (Review)
Review
Thymomas are the most frequently encountered tumors of the mediastinum and often present with either localized or locally advanced disease. The prognosis in thymoma has been consistently shown to correspond to the invasiveness of the tumor (as represented by the Masaoka stage of the tumor) and the completeness of surgical resection. Because treatment with a variety of different chemotherapy regimens has demonstrated radiographic response rates greater than 50% in patients with advanced thymoma, a number of investigators have explored the use of preoperative (induction, neoadjuvant) therapy for patients with locally advanced thymoma. In this review, we summarize the published experience with preoperative therapy for thymoma and discuss ongoing clinical trials exploring multimodality therapy for treatment of locally advanced thymoma.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Humans; Prognosis; Remission Induction; Thymoma; Thymus Neoplasms
PubMed: 20859127
DOI: 10.1097/JTO.0b013e3181f20e90 -
Internal Medicine (Tokyo, Japan) 2008Patients with thymoma are likely to present with associated autoimmunologic disorders. The occurrence of syndrome of inappropriate antidiuretic hormone (SIADH)... (Review)
Review
Patients with thymoma are likely to present with associated autoimmunologic disorders. The occurrence of syndrome of inappropriate antidiuretic hormone (SIADH) attributable to thymoma is extremely rare. We herein present an extremely rare case of a 59-year-old man patient who was discovered to have malignant thymoma associated with myasthenia gravis, Graves' disease, and SIADH. He was admitted for evaluation and treatment of hyponatremia (Na 125 mEq/l). SIADH was diagnosed, and thymoma was identified as its cause. The patient was also found to have both Graves' disease and myasthenia gravis. The hyponatremia was normalized with water restriction and 3% saline therapy before thymectomy. The thymic tumor was a Masaoka stage III thymoma that resulted in direct invasion to the wall of the innominate vein, but there was no finding of invasion to other mediastinal organs. Complete thymectomy with innominate vein graft was performed. Microscopic histopathology findings corresponded to those of a mixed-type thymoma and type B2. However, immunohistochemical stain for antidiuretic hormone was negative in the tumor cells. Adjuvant radiation therapy was employed postoperatively, and the patient's postoperative recovery was uneventful. He subsequently reached a euthyroid state. And the reversal to normal sodium and osmolality levels was continued after the tumor removal without any further management for hyponatremia. The observation of this interesting case and a literature review provided us with the opportunity to explore the pathogenesis and clinical aspects of thymoma-related autoimmune and/or endocrine disorders which must be suspected in patients with thymoma.
Topics: Graves Disease; Humans; Immunohistochemistry; Inappropriate ADH Syndrome; Male; Middle Aged; Myasthenia Gravis; Thymectomy; Thymoma; Thymus Neoplasms; Vasopressins
PubMed: 18520111
DOI: 10.2169/internalmedicine.47.0838 -
Medicina (Kaunas, Lithuania) Sep 2021: Thymomas are associated with a high frequency of paraneoplastic manifestations. Paraneoplastic syndrome (PNS) with thymoma presents a challenge to clinicians because...
: Thymomas are associated with a high frequency of paraneoplastic manifestations. Paraneoplastic syndrome (PNS) with thymoma presents a challenge to clinicians because of the need to decipher the association between the presenting symptoms and the underlying tumor. The condition most commonly noted in patients with PNS with thymoma is myasthenia gravis. Other common autoimmune diseases that may present as PNS include systemic lupus erythematosus, pure red cell aplasia, and Good syndrome. Seventy-six percent of patients with PNS-associated thymoma experience resolution of PNS after curing thymoma. : A 37-year-old man with a two-month fever accompanied by polyarthritis accidently found thymoma after contrast computed tomography scans of his chest. He accepted Video assisted thoracoscopic surgery with resection of thymoma. : Fever and polyarthritis resolved after operation but recurred in five days due to cytomegalovirus viremia, which might be predisposed by previous antibiotics treatment before the diagnosis of thymoma. : Patients with a thymoma also have a high frequency of PNS, and the most frequent condition found in patients with PNS-associated thymoma is myasthenia gravis. Fever with polyarthritis has been rarely reported as a symptom of PNS-associated thymoma. Here we reported an unusual case of PNS mimicking reactive arthritis with thymoma, as diagnosed based on the patient's clinical progression, imaging examination, and laboratory tests. The patient died of his comorbidities, and his death may have been related to long-term antibiotic use and consequent intestinal dysbiosis. This challenging case may help to inform clinicians of the need for detailed work-up of fever with unknown origin in the presence of chronic polyarthritis to prevent the overdiagnosis of inflammatory arthritis or rheumatic disease and avoid further comorbidities. Detailed work-up should include the patient's history of infections, inflammation, and malignant or nonmalignant tumors.
Topics: Adult; Arthritis, Reactive; Humans; Male; Myasthenia Gravis; Neoplasm Recurrence, Local; Paraneoplastic Syndromes; Thymoma; Thymus Neoplasms
PubMed: 34577855
DOI: 10.3390/medicina57090932 -
Journal of the American Veterinary... Jul 2018
Topics: Animals; Autopsy; Cat Diseases; Cats; Diagnosis, Differential; Dyspnea; Female; Thymoma; Thymus Neoplasms
PubMed: 29963950
DOI: 10.2460/javma.253.2.173 -
The Journal of Cardiovascular Surgery Feb 2006Since World Health Organization (WHO) histologic typing of tumors of the thymus publication in 1999 only a few studies correlated this classification with the clinical...
AIM
Since World Health Organization (WHO) histologic typing of tumors of the thymus publication in 1999 only a few studies correlated this classification with the clinical features of the patients. We present the results of a retrospective analysis on patients, operated on for a thymoma, whose specimens were available, to compare the WHO thymoma histologic classification to the clinical behavior of the tumors.
METHODS
The specimens of 69 patients, who underwent surgical treatment between 1983 and 1998, were analyzed, comparing the clinical features of the patients and the hystological typing of the neoplasm, according to the WHO classification. A survival analysis of clinical and pathological prognostic factors was carried out.
RESULTS
The incidence of thymus-related syndrome was related to the histological subtype and increases progressively from A to B3, while in C subtype the incidence was nihl. With a mean follow-up of 108 months (range 54-239 months), we experienced 6 intrathoracic recurrencies, 3 of those were intrapleuric and 3 mediastinal. At the last follow-up, 52 patients were alive; 1 with disease. Five deaths were related to the tumor (2 mediastinal and 3 intrapleuric relapses). Actuarial five-year and ten-year survival was 95% and 88.9%. Because of the absence of deaths related to thymomas in most samples it was not possible to perform a comparison among different histological types and different clinical stages.
CONCLUSIONS
The WHO histologic classification seems to correlate with the incidence of thymus related syndromes and the clinical stage of Masaoka. Despite the higher incidence of recurrences in type B3 and C thymoma the WHO classification did not prove to be a prognostic factor.
Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Male; Middle Aged; Prognosis; Retrospective Studies; Thymoma; Thymus Neoplasms
PubMed: 16434954
DOI: No ID Found -
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 -
Zhongguo Fei Ai Za Zhi = Chinese... Feb 2014
Topics: Humans; Thymoma; Thymus Neoplasms
PubMed: 24581155
DOI: 10.3779/j.issn.1009-3419.2014.02.02 -
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