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ESMO Open Oct 2023Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the...
BACKGROUND
Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the genomic profiles of TETs. Herein, we investigated the genomic characteristics of TETs evaluated in a large comprehensive genomic profiling database in a real-world setting.
METHODS
We included data from two different cohorts: Foundation Medicine Inc. (FMI) in the United States and the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. Samples profiled were examined for all classes of alterations in 253 genes targeted across all assays. Tumor mutational burden (TMB) and microsatellite instability (MSI) were also evaluated.
RESULTS
A total of 794 patients were collected in our study, including 722 cases from FMI and 72 cases from C-CAT. In the FMI data, CDKN2A (39.9%), TP53 (30.2%) and CDKN2B (24.6%) were frequently altered in thymic carcinoma, versus TP53 (7.8%), DNMT3A (6.8%), and CDKN2A (5.8%) in thymoma. TMB-high (≥10 mutations/Mb) and MSI were present in 7.0% and 2.3% of thymic carcinomas, and 1.6% and 0.3% of thymomas, respectively. Within C-CAT data, CDKN2A (38.5%), TP53 (36.5%) and CDKN2B (30.8%) were also frequently altered in thymic carcinoma, while alterations of TSC1, SETD2 and LTK (20.0% each) were found in thymoma.
CONCLUSIONS
To the best of our knowledge, this is the largest cohort in which genomic alterations, TMB and MSI status of TETs were investigated. Potential targets for treatment previously unbeknownst in TETs are identified in this study, entailing newfound opportunities to advance therapeutic development.
Topics: Humans; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Genomics
PubMed: 37703595
DOI: 10.1016/j.esmoop.2023.101627 -
Orvosi Hetilap Jun 2023Good syndrome is an infrequent and unique clinical entity of associated thymoma and immunodeficiency, first described almost 70 years ago. It is characterized by...
Good syndrome is an infrequent and unique clinical entity of associated thymoma and immunodeficiency, first described almost 70 years ago. It is characterized by increased susceptibility to recurrent invasive bacterial and opportunistic infections as well as autoimmune and malignant diseases with an omnious prognosis. The affected patients are mainly middle-aged persons. The most consistent immunological abnormalities are hypogammaglobulinemia and reduced/absent B cells. More recently it was classified as an acquired combined (T, B) immunodeficiency and labelled as a phenocopy. This complex immunocompromised condition can lead to heterogenous clinical phenotypes, making the diagnosis rather challenging. The thymoma is mainly benign, and an incidental finding. Since the thymus plays a critical role in the development of the immune system, the altered tissue structure and microenvironment in thymoma can both predispose to manifestation of immunodeficiency and autoimmunity. The etiopathogenesis of the disease is still unclear, but it is assumed that epigenetic and acquired genetic factors can be highly responsible for its evolvement. Currently there is no specific therapy for Good syndrome. In addition to thymectomy, control of infections, possibly secondary prevention, and regular immunoglobulin replacement are recommended. Orv Hetil. 2023; 164(22): 859-863.
Topics: Humans; Thymoma; Immunologic Deficiency Syndromes; Thymus Neoplasms; Agammaglobulinemia; Lymphopenia; Tumor Microenvironment
PubMed: 37270775
DOI: 10.1556/650.2023.32800 -
Thoracic Cancer Jun 2021Thymomas are the most common type of anterior mediastinal tumors. Calcification is sometimes observed in thymomas using computed tomography (CT), and it is more frequent...
BACKGROUND
Thymomas are the most common type of anterior mediastinal tumors. Calcification is sometimes observed in thymomas using computed tomography (CT), and it is more frequent in invasive thymomas than in noninvasive thymomas. However, the significance of calcification in thymomas remains unknown. This study aimed to evaluate the significance of calcification in thymomas on invasiveness to surrounding organs and investigate the characteristics of thymoma cases with calcification at our institution.
METHODS
We included thymoma patients treated at our institution between 2000 and 2016, and evaluated their characteristics, including demographics, calcification on CT, histology, Masaoka stage, and myasthenia gravis status. The patients were categorized into calcification (C) and noncalcification (NC) groups.
RESULTS
Among 51 included patients, 11 (21.6%) had calcification. A higher proportion of group C patients had World Health Organization histological type B2 and B3 tumors (high-risk) than type A, AB, and B1 tumors (low-risk; p = 0.0477). The number of patients with Masaoka stages III and IV were significantly higher in the C group than in the NC group (p < 0.0001). The C group patients had significantly higher rates of invasion to the mediastinal pleura, pericardium, lung, phrenic nerve, and chest wall and pleural dissemination than the NC group patients.
CONCLUSIONS
Calcification reflects invasiveness of tumors to surrounding organs and tissues, and may thus predict thymoma stage and histologically high-risk thymomas. Calcification in thymomas may also predict the pathological stage and help decide therapeutic methods and surgical approaches to treat thymomas based on the calcification status according to CT findings.
Topics: Calcinosis; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Thymoma
PubMed: 33955164
DOI: 10.1111/1759-7714.13964 -
European Journal of Cardio-thoracic... Jun 2016In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced... (Review)
Review
In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced tumour stages. Complete surgical resection (R0) remains the standard therapeutic approach for almost all a priori resectable mediastinal tumours as defined by preoperative standard computed tomography (CT). If lymphoma or germ-cell tumours are differential diagnostic considerations, biopsy may be indicated. Resection status is the most important prognostic factor in thymoma and TC, followed by tumour stage. Advanced (Masaoka-Koga stage III and IVa) tumours require interdisciplinary therapy decisions based on distinctive findings of preoperative CT scan and ancillary investigations [magnetic resonance imaging (MRI)] to select cases for primary surgery or neoadjuvant strategies with optional secondary resection. In neoadjuvant settings, octreotide scans and histological evaluation of pretherapeutic needle biopsies may help to choose between somatostatin agonist/prednisolone regimens and neoadjuvant chemotherapy as first-line treatment. Finally, a multimodality treatment regime is recommended for advanced and unresectable thymic tumours. In conclusion, advanced stage thymoma and TC should preferably be treated in experienced centres in order to provide all modern diagnostic tools (imaging, histology) and innovative therapy techniques. Systemic and local (hyperthermic intrathoracic chemotherapy) medical treatments together with extended surgical resections have increased the therapeutic options in patients with advanced or recurrent thymoma and TC.
Topics: Combined Modality Therapy; Humans; Magnetic Resonance Imaging; Neoplasm Staging; Thymectomy; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed
PubMed: 26670806
DOI: 10.1093/ejcts/ezv426 -
Scientific Reports Feb 2023To determine the prognostic CT features in patients with untreated thymic epithelial tumors (TETs). Clinical data and CT imaging features of 194 patients with...
To determine the prognostic CT features in patients with untreated thymic epithelial tumors (TETs). Clinical data and CT imaging features of 194 patients with pathologically confirmed TETs were retrospectively reviewed. The subjects included 113 male and 81 female patients between 15 and 78 years of age, with a mean age of 53.8 years. Clinical outcomes were categorized according to whether relapse, metastasis or death occurred within 3 years after the first diagnosis. Associations between clinical outcomes and CT imaging features were determined using univariate and multivariate logistic regression analyses, while the survival status was analyzed by Cox regression. In this study, we analyzed 110 thymic carcinomas, 52 high-risk thymomas and 32 low-risk thymomas. Percentages of poor outcome and patient death in thymic carcinomas were much higher than those in patients with high-risk and low-risk thymomas. In the thymic carcinomas groups, 46 patients (41.8%) experienced tumor progression, local relapse or metastasis and were categorized as having poor outcomes; vessel invasion and pericardial mass were confirmed to be independent predictors by logistic regression analysis (p < 0.01). In the high-risk thymoma group, 11 patients (21.2%) were categorized as having poor outcomes, and the CT feature pericardial mass was confirmed to be an independent predictor (p < 0.01). In survival analysis, Cox regression showed that CT features of lung invasion, great vessel invasion, lung metastasis and distant organ metastasis were independent predictors for worse survival in the thymic carcinoma group (p < 0.01), while lung invasion and pericardial mass were independent predictors for worse survival in high-risk thymoma group. No CT features were related to poor outcome and worse survival in the low-risk thymoma group. Patients with thymic carcinoma had poorer prognosis and worse survival than those with high-risk or low-risk thymoma. CT can serve as an important tool for predicting the prognosis and survival of patients with TETs. In this cohort, CT features of vessel invasion and pericardial mass were related to poorer outcomes in those with thymic carcinoma and pericardial mass in those with high-risk thymoma. Features including lung invasion, great vessel invasion, lung metastasis and distant organ metastasis indicate worse survival in thymic carcinoma, whereas lung invasion and pericardial mass indicate worse survival in high-risk thymoma.
Topics: Humans; Male; Female; Middle Aged; Thymoma; Prognosis; Retrospective Studies; Neoplasm Recurrence, Local; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Lung Neoplasms
PubMed: 36801902
DOI: 10.1038/s41598-023-30041-z -
Journal of B.U.ON. : Official Journal... 2021Thymic epithelial tumors represent 0.2-1.5% among all malignant neoplasms. They are slow-growing tumors with an overall recurrence rate around 10% and 90% of them are... (Review)
Review
Thymic epithelial tumors represent 0.2-1.5% among all malignant neoplasms. They are slow-growing tumors with an overall recurrence rate around 10% and 90% of them are located in the anterior mediastinum. In this review we focused on the classification, histopathology, molecular pathology and prognosis of thymic epithelial tumors, mainly thymoma and thymic carcinoma.
Topics: Carcinoma; Humans; Neoplasms, Glandular and Epithelial; Prognosis; Thymoma; Thymus Neoplasms
PubMed: 34564969
DOI: No ID Found -
Vnitrni Lekarstvi 2021A thymoma belongs to rather rare tumors, although it holds the first place among primary mediastinal tumors in adults. The biological characteristics of thymomas are...
A thymoma belongs to rather rare tumors, although it holds the first place among primary mediastinal tumors in adults. The biological characteristics of thymomas are considerably divergent. The tumors are usually asymptomatic at the begining, later due to a local spread, symptoms from the infiltration or compression of adjacent structures arise, they metastasize rarely. Thymomas are often associated with various autoimmune or endocrinologic diseases. The authors present case of the patient with less common paraneoplasia - autoimmune hemolytic anemia (AIHA). Main strategy of treatment thymom with AIHA isn´t clear. The most important seems to be the early started corticotherapy. Achieving remission of secondary AIHA has importace in following therapy of thymoma - surgical resection or chemotherapy. Thymectomy has positive effect on the course of associated paraneoplastic syndromes and prognosis in general.
Topics: Adult; Anemia, Hemolytic, Autoimmune; Humans; Paraneoplastic Syndromes; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 34275310
DOI: No ID Found -
Journal of Thoracic Oncology : Official... Dec 2023A TNM-based system for all types of thymic epithelial tumors was introduced in the eighth edition of the TNM classification of thoracic malignancies. The Thymic Domain...
The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposal for a Stage Classification for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.
INTRODUCTION
A TNM-based system for all types of thymic epithelial tumors was introduced in the eighth edition of the TNM classification of thoracic malignancies. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer, composed of multispecialty international experts, was charged to develop proposals for the ninth edition. This article outlines the proposed definitions for the T, the N, and the M components and their combination into stage groups.
METHODS
A large central database of 11,347 patients with thymic epithelial tumors was assembled thanks to the contribution of the major thymic organizations worldwide and analyses were carried out for the T, the N, and the M components and the stage groups. Overall survival was the outcome measure for patients with completely and incompletely resected tumors, and recurrence for those with complete resection. When the number of patients was sufficient, analyses were performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors.
RESULTS
Tumor size is included in the T1 category as T1a (≤5cm) and T1b (>5 cm); the mediastinal pleura is dropped as a T descriptor; invasion of the lung or phrenic nerve is reclassified as T2 (instead of T3). No changes are proposed for the N and the M components from the eighth edition. The stage groups remain the same.
CONCLUSIONS
The proposed changes for the ninth edition of the TNM classification set the stage for further progress in the future for these rare tumors.
Topics: Humans; Neoplasm Staging; Lung Neoplasms; Prognosis; Myeloma Proteins; Thymus Neoplasms; Thymoma; Neuroendocrine Tumors; Neoplasms, Glandular and Epithelial
PubMed: 37689391
DOI: 10.1016/j.jtho.2023.09.002 -
Pediatric Blood & Cancer Jun 2021Thymic tumors are epithelial tumors arising from the anterior mediastinum and constitute 0.2-1.5% of all adult malignancies but are exceptional in pediatric population....
Thymic tumors are epithelial tumors arising from the anterior mediastinum and constitute 0.2-1.5% of all adult malignancies but are exceptional in pediatric population. Thymic epithelial tumors (TETs) encompass a variety of histologic subtypes associated with different clinical outcomes. Due to its rarity in children, TETs' management requires a multidisciplinary approach. However, prognosis remains still poor, especially among patients with thymic carcinoma. This study presents the internationally recognized recommendations for the diagnosis and treatment of thymic tumors in children and adolescents, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) group within the EU-funded project Paediatric Rare Tumours Network - European Registry (PARTNER).
Topics: Adolescent; Adult; Child; Humans; Neoplasms, Glandular and Epithelial; Prognosis; Thymoma; Thymus Neoplasms
PubMed: 33881200
DOI: 10.1002/pbc.29042 -
Thoracic Cancer May 2021Thymomas and thymic carcinomas are the most common tumor types among anterior mediastinal lesions. However, the relationship between molecular aberrations and thymoma...
BACKGROUND
Thymomas and thymic carcinomas are the most common tumor types among anterior mediastinal lesions. However, the relationship between molecular aberrations and thymoma patients are poorly understood, especially abnormal changes in the expression profiles of circRNAs. The purpose of the present study was to investigate the expression profiles of circRNAs in thymoma patients and their possible roles in the pathogenesis of thymoma.
METHODS
Diseased tissues and surrounding normal thymic tissues in two thymoma patients were collected for circRNA sequencing. The top four upregulated circRNAs were selected as candidates and further validated with RT-PCR in 20 thymoma patients. Gene ontology and signal transduction network analyses of circRNA-related mRNAs were performed to analyze the functional properties. Survival analysis of their parental genes were also carried out to evaluate the clinical value of differentially expressed circRNA.
RESULTS
A total of 73 circRNAs were differentially expressed in thymoma tissues using high-throughput sequencing. Among these circRNAs, hsa_circ_0001173, hsa_circ_0007291, hsa_circ_0003550, and hsa_circ_0001947 were significantly upregulated in thymoma tissues compared with normal thymic tissues. We identified that these four circRNA-related mRNAs were involved in cell-cell adhesion, MAPK pathways, and TNF pathway, which may contribute to the pathological immune disorder in thymoma. Finally, we also found that SCAP (hsa_circ_0007291 parental gene) and AFF2 (hsa_circ_0001947 parental gene) were all significantly related with progression-free survival (PFS) of thymoma patients in a Kaplan-Meier plot (p-value <0.05).
CONCLUSIONS
The expression levels of hsa_circ_0001173, hsa_circ_0007291, hsa_circ_0003550, and hsa_circ_0001947 were significantly upregulated and positively correlated with immune imbalance in thymoma patients.
Topics: Humans; RNA, Circular; Survival Analysis; Thymoma
PubMed: 33704915
DOI: 10.1111/1759-7714.13873