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Characteristics of thymoma patients with suspected immunodeficiency 

Characteristics of thymoma patients with suspected immunodeficiency 

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Several immune disorders are often associated with thymoma. The aim of this study was to analyze the correlation between clinicopathological features of Thai patients with thymoma and concomitant immune-mediated diseases. Medical records of 87 patients diagnosed with thymoma during a 10-year period were retrospectively reviewed. Peripheral blood T...

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... were nine patients (10.3 % of thymoma patients) with clinical symptoms suggesting immunodeficiency sta- tus as shown in Table 3. Unexplained diffuse cylindrical Arch. ...

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... This type of pneumonia is caused by a Gram -, obligate intracellular bacterium called C. psittaci, typically detected using metagenomics next-generation sequencing (mNGS) examination. Patients with thymoma are more susceptible to immune dysfunction compared with individuals with common pneumonia (2), and they have an increased risk of infection with C. psittaci. In patients with thymoma, the entry of C. psittaci in the bloodstream can involve the lungs, leading to pneumonia and potentially affecting multiple organs, resulting in organ failure. ...
... Additionally, during the diagnostic process for identifying the pathogen, a mediastinal mass was incidentally identified. C. psittaci pneumonia accounts for ~1% of community-acquired pneumonia cases (2). Most patients with this condition have a history of contact with infected birds or poultry (5). ...
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The case of a patient with type B3 thymomacomorbid with Chlamydia psittaci (C. psittaci) pneumonia exhibiting rare features is presented in the current report. The patient was admitted at the Second Affiliated Hospital of Jiaxing University (Jiaxing, China) with a history of direct contact with poultry. Clinical manifestations included fever, shivers, cough, fatigue and poor appetite. Chest computed tomography (CT) indicated right lung pneumonia, while metagenomics next-generation sequencing using bronchoalveolar lavage fluid confirmed infection with C. psittaci. Additionally, positron emission tomography-CT suggested the presence of thymoma. After surgery and treatment with doxycycline and imipenem cilastatin, the patient was discharged showing signs of improvement.
... Up to 40% of human patients with TET have a concurrent neoplasia and 27% of dogs with TET had a second non-thymic tumour at the time of the TET diagnosis with another 14% developing another neoplasm during the follow-up period (Robat et al., 2013, Thongprayoon et al., 2013. Robat et al. (2013) reported the presence of a second non-thymic tumour at the time of TET diagnosis was associated with a significant decrease in survival time, whereas no negative influence on survival time was noted if another tumour developed later. ...
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OBJECTIVES: To describe the clinical presentation, treatment and outcomes of cats diagnosed with thymic epithelial tumours and to determine prognostic factors for survival and recurrence. MATERIALS AND METHODS: Clinical records of cats diagnosed with a thymic epithelial tumour between 1999 and 2021 at three referral institutions were retrospectively reviewed. RESULTS: Sixty-four cats were included. Paraneoplastic syndromes were present in nine cats and metastatic disease was seen in two cats, one at diagnosis and one at the time of recurrence. Median tumour diameter was 6 cm (range, 2 to 15) and a cystic appearance was described on imaging in 25 cats. Surgical excision was attempted in 54 cats with a perioperative mortality rate of 11%. Median survival time for cats surviving to hospital discharge was 897 days (range, 21 to 3322). The 1-, 2-and 5-year survival rates for surgically treated thymic epithelial tumour were 86%, 70% and 66%, respectively. Survival was longer for cats with Masaoka-Koga stage I and II tumours compared to stages III and IV (1366 days versus 454 days; P=0.002). Masaoka-Koga stage was the only significant prognostic factor detected on multivariable analysis, with stage III and IV tumours associated with increased risk of death (hazard ratio: 5.67, 95% con dence interval: 1.29 to 24.91, P=.021). Tumour recurrence occurred in 11 cats at a median of 564 days (range, 93 to 1095); no significant prognostic factors for recurrence were identified. CLINICAL SIGNIFICANCE: Cats with thymic epithelial tumours had a good long-term prognosis following surgery. Tumour recurrence can occur late in the disease course and ongoing monitoring should therefore be considered. Masaoka-Koga stage may in uence survival time and could be used to predict outcome .
... For example, patients with THYM had a significantly higher percentage of regulatory T cells and a lower percentage of CD4 + naïve T cells compared with healthy controls. Aberrant immunologic disorders and altered T-cell subsets in THYM were significantly associated with clinical phenotype and prognosis (Thongprayoon et al., 2013). TMB appears to be a new biomarker for predicting the effects of and immune response to immunotherapy. ...
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Purpose: The pathogenesis of thymoma (THYM) remains unclear, and there is no uniform measurement standard for the complexity of THYM derived from different thymic epithelial cells. Consequently, it is necessary to develop novel biomarkers of prognosis estimation for patients with THYM. Methods: Consensus clustering and single-sample gene-set enrichment analysis were used to divide THYM samples into different immunotypes. Differentially expressed genes (DEGs) between those immunotypes were used to do the Kyoto Encyclopedia of Genes and Genomes analysis, Gene Ontology annotations, and protein-protein interaction network. Furthermore, the survival-related DEGs were used to construct prognostic model with lasso regression. The model was verified by survival analysis, receiver operating characteristic curve, and principal component analysis. Furthermore, the correlation coefficients of stemness index and riskscore, tumor mutation burden (TMB) and riskscore, drug sensitivity and gene expression were calculated with Spearman method. Results: THYM samples were divided into immunotype A and immunotype B. A total of 707 DEGs were enriched in various cancer-related or immune-related pathways. An 11-genes signature prognostic model (CELF5, ODZ1, CD1C, DRP2, PTCRA, TSHR, HKDC1, KCTD19, RFX8, UGT3A2, and PRKCG) was constructed from 177 survival-related DEGs. The prognostic model was significantly related to overall survival, clinical features, immune cells, TMB, and stemness index. The expression of some genes were significantly related to drug sensitivity. Conclusion: For the first time, a prognostic model of 11 genes was identified based on the immune microenvironment in patients with THYM, which may be helpful for diagnosis and prediction. The associated factors (immune microenvironment, mutation status, and stemness) may be useful for exploring the mechanisms of THYM.
... Thymoma is a mediastinal tumor originating from the thymus epithelial cells and accounting for approximately 25% of mediastinal tumors. 1 Approximately 30% of patients with thymoma also have myasthenia gravis (MG). 2 Recently, studies have suggested that thymoma with autoimmune disorders is likely mediated by the dysfunction in central tolerance and immunoregulation. 3 However, the precise mechanisms underlying the process of thymoma-related disorders have not been clarified. ...
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Background To investigate the gene expression profile of a set of candidate genes for a better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without myasthenia gravis. Methods Thymoma patients and thymoma patients with myasthenia gravis were analyzed using microarray profiling to identify significant changes in gene expression of autoimmune regulator pathway genes including AIRE, IL‐7R, CHRNA3, SYMD1, THRA, and CAV3. Results Across all of our samples, we found that 1484 mRNAs were upregulated and 770 were downregulated in thymoma patients compared with thymoma with myasthenia gravis patients. Gene ontology and pathway analysis revealed that a large number of genes participated in cellular functions for humoral immune response, sequence‐specific DNA binding RNA polymerase II transcription factor activity, positive regulation of gene expression, regulation of neuron projection development, extracellular ligand‐gated ion channel activity, positive regulation of striated muscle cell differentiation, and regulation of nuclear factor‐kappaB import into the nucleus. Conclusion Our results revealed genetic differences between thymomas and myasthenia gravis, and identified the key candidate genes/pathways for molecular mechanism.
... Peripheral Vδ2 T cells can secrete IFN-γ [15], but the level of IFN-γ secreted by γδT cells from our GS patient was significantly lower compared with HCs, and this difference may be involved with the observed mild alternations in the CD4 + T cell-derived IFN-γ levels in this patient ( Figure 7). Because IFN-γ production by CD8 + T cells may partially compensate for insufficient cellular IFN-γ [22], we also measured the expression levels of IFN-γ produced by these cells. Data from numerous cytokine profiles suggest that the recurrent respiratory infections suffered by our GS patient could be related to the intracellular expressions of IL-17A and IFN-γ. ...
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Good’s syndrome (GS) is often accompanied by recurrent respiratory infections and chronic diarrhea. The main purpose was to evaluate the peripheral immune status of a GS patient after thymoma resection. Twenty healthy volunteers were recruited as healthy controls (HCs). Flow cytometry was applied to determine the proportions of circuiting CD4 ⁺ T cells, CD8 ⁺ T cells, γδ T cells, and regulatory T (Treg) cells in our GS patient. We also examined the proliferation capability of ex vivo CD4 ⁺ T cells and detected the levels of cytokines interferon- (IFN-) γ and interleukin-17A secreted by ex vivo immune cells from this GS patient. Compared with healthy control subjects, this GS patient had fewer B cells, an inverted ratio of CD4 ⁺ /CD8 ⁺ cells, and more Treg cells in his peripheral blood. Additionally, the patient’s V δ 2 T cell levels were significantly decreased despite having a normal percentage of γδ T cells. Ex vivo peripheral CD4 ⁺ T cells from the patient showed insufficient proliferation and division potential as well as excessive expression of PD-1. Moreover, IFN- γ was predominantly derived from CD8 ⁺ T cells in this GS patient, rather than from CD4 ⁺ T cells and γδ T cells. This GS patient had impaired T and B cell immunological alternations and cytokine disruptions after thymectomy. Detailed research should focus on therapies that can adjust the immune status in such patients for a better outcome.
... This finding was consistent with those for previously reported paraneoplastic syndromes in humans and dogs with thymomas. 1,3,4,19 Two dogs with thymoma in the present study appeared to develop postoperative myasthenic decompensation or myasthenic crisis, which precipitated their deaths. Postoperative development of myasthenia gravis has been reported for human and veterinary patients undergoing thymectomy, but postoperative myasthenic crisis has not been reported for veterinary patients undergoing thymectomy. ...
Article
OBJECTIVE To characterize clinical findings, surgical procedures, complications, and outcomes in dogs undergoing extirpation of masses from the cranial mediastinum via video-assisted thoracic surgery (VATS) and establish preliminary guidelines for case selection when considering VATS for thymectomy in dogs. DESIGN Retrospective case series. ANIMALS 18 client-owned dogs that underwent extirpation of a cranial mediastinal mass by means of VATS at 5 academic referral hospitals from 2009 through 2014. PROCEDURES Medical records were reviewed and data extracted regarding signalment, clinical signs, physical examination findings, diagnostic imaging results, surgical approach and duration, cytologic and histologic examination results, complications, outcome, and cause of death, when applicable. RESULTS 16 dogs had a thymoma, 1 had thymic anaplastic carcinoma, and 1 had hemangiosarcoma. Seven had both megaesophagus and myasthenia gravis. Median approximate tumor volume was 113.1 cm³ (interquartile range, 33.5 to 313.3 cm³). Median duration of VATS was 117.5 minutes (interquartile range, 91.5 to 136.3 minutes). Conversion to an open thoracic surgical procedure was required for 2 dogs, 1 of which died during surgery. Median survival time following VATS for dogs with thymoma and concurrent myasthenia gravis and megaesophagus was 20 days. Dogs with thymoma without paraneoplastic syndrome survived for ≥ 60 days, and none of these dogs died of disease-related causes. CONCLUSIONS AND CLINICAL RELEVANCE VATS appeared to be an acceptable approach for extirpation of masses from the cranial mediastinum in dogs under certain conditions. Dogs with myasthenia gravis and megaesophagus had a poor postoperative outcome.
... In assessing this case, we cannot exclude the possibility that the patient's genetic background or underlying conditions may have played a role in the control of WNV infection and persistence. Although patients with thymoma B2 may, in rare cases, exhibit hypogammaglobulinemia and cellular immune dysfunction (11), this patient was considered immunocompetent because his medical history and follow-up after this infection did not show any indication of immune deficiency. The change in neutrophil count during acute infection is intriguing because neutrophils have been shown to serve as a reservoir for WNV replication during early infection and to contribute to viral clearance at a later stage of illness (12). ...
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A mutation leading to substitution of a key amino acid in the prM protein of West Nile virus (WNV) occurred during persistent infection of an immunocompetent patient. WNV RNA persisted in the patient’s urine and serum in the presence of low-level neutralizing antibodies. This case demonstrates active replication of WNV during persistent infection.
... Montella et al. [2] studied 18 thymoma patients of which 9 patients had a B-cell lymphopenia and 4 patients had a low T-lymphocyte number, while only 4 patients had hypogammaglobulinemia. Thongprayoon et al. [17] studied 87 thymoma patients. Eight patients with clinical symptoms suspicious for an immunodeficiency were tested and although 5 patients had an inverted CD4/CD8 ratio and 3 had B-cell lymphopenia, only one patient had hypogammaglobulinemia. ...
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Good syndrome (GS) or thymoma-associated immunodeficiency, is a rare condition that has only been studied in retrospective case series. General consensus was that GS has a worse prognosis than other humoral immunodeficiencies. In this study, physicians of GS patients completed two questionnaires with a two year interval with data on 47 patients, 499 patient years in total. Results on epidemiology, disease characteristics, and outcome are presented. Mean age at diagnosis was 60years and median follow-up from onset of symptoms was 9years. There was a high frequency of respiratory tract infections due to encapsulated bacteria. Median survival was 14years. Survival was reduced compared to age-matched population controls (5-year survival: 82% versus 95%, p=0.008). In this cohort survival was not associated with gender (HR 0.9, 95% CI 0.3–3.0), autoimmune diseases (HR 2.9, 95% CI 0.8–10.1) or immunosuppressive use (HR 0.3, 95% CI: 0.1–1.2).
... Common examples are autoimmune manifestations, such as myasthenia gravis and giant cell myocarditis (1,2), combined B and T cell immunodeficiency (Good's syndrome) (3), an absolute lymphocytosis, or a relative increase in circulating naive T cells (4,5). Additionally, an isolated T cell immunodeficiency with unknown pathogenesis has been described that may be more frequent than classical Good's syndrome (6)(7)(8). ...
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The mechanisms underlying thymoma-associated immunodeficiency are largely unknown, and the significance of increased blood γδ Τ cells often remains elusive. In this study we address these questions based on an index patient with thymoma, chronic visceral leishmaniasis, myasthenia gravis, and a marked increase of rare γδ T cell subsets in the peripheral blood. This patient showed cutaneous anergy, even though he had normal numbers of peripheral blood total lymphocytes as well as CD4(+) and CD8(+) T cells. Despite his chronic infection, analyses of immunophenotypes and spectratyping of his lymphocytes revealed an unusual accumulation of naive γδ and αβ T cells, suggesting a generalized T cell activation defect. Functional studies in vitro demonstrated substantially diminished IL-2 and IFN-γ production following TCR stimulation of his "untouched" naive CD4(+) T cells. Biochemical analysis revealed that his γδ and αβ T cells carried an altered TCR complex with reduced amounts of the ζ-chain (CD247). No mutations were found in the CD247 gene that encodes the homodimeric ζ protein. The diminished presence of CD247 and increased numbers of γδ T cells were also observed in thymocyte populations obtained from three other thymoma patients. Thus, our findings describe a novel type of a clinically relevant acquired T cell immunodeficiency in thymoma patients that is distinct from Good's syndrome. Its characteristics are an accumulation of CD247-deficient, hyporresponsive naive γδ and αβ T cells and an increased susceptibility to infections. Copyright © 2015 by The American Association of Immunologists, Inc.
... 29 In humans, several other immune-mediated diseases are often associated with the presence of a thymoma. 30 Similar observations were made in a previous study 6 and in the present study; in the latter, 8 dogs had concurrent immune-mediated diseases such as immune-mediated thrombocytopenia, keratoconjunctivitis sicca, perianal fistula, hypothyroidism, mastica-SMALL ANIMALS/ EXOTIC tory muscle myositis, hypothyroidism, polyarthritis, or diabetes mellitus, all of which support a deficiency in immune response. ...
... Up to 40% of humans with thymomas may also have concurrent neoplasms. 30 In the present study, 27% of dogs had a second nonthymic tumor at the time of thymoma diagnosis and another 14% later developed another neoplasm. Regular and thorough follow-up examinations, including thoracic and abdominal imaging, should therefore be recommended for dogs with thymoma. ...
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Objective: To describe clinical signs, diagnostic findings, treatment, and outcome and determine factors associated with survival time for dogs with thymoma. Design: Multi-institutional retrospective case series. Animals: 116 dogs with thymoma. Procedures: Medical records were searched for information regarding signalment, physical examination findings, results of laboratory testing and diagnostic imaging, medical and surgical treatment, and survival data. Results: Of the 116 dogs with thymoma, 44 (38%) were Labrador Retrievers and Golden Retrievers. Twenty of 116 (17%) dogs had signs of myasthenia gravis (diagnosis was confirmed for 13 dogs). At the time of thymoma diagnosis, 40 (34%) dogs had hypercalcemia, 8 (7%) dogs had a concurrent immune-mediated disease, and 31 (27%) dogs had another tumor; 16 (14%) dogs developed a second nonthymic tumor at a later date. Tumor excision was performed for 84 dogs, after which 14 (17%) had tumor recurrence; prognosis was good for dogs undergoing a second surgery. Median survival time with and without surgical treatment was 635 and 76 days, respectively. Presence of another tumor at the time of thymoma diagnosis, lack of surgical excision, and higher pathological stage were significantly associated with shorter survival time. Hypercalcemia and presence of myasthenia gravis or megaesophagus at the time of thymoma diagnosis, histopathologic subtype of thymoma, or tumor development at a later date was not associated with survival time. Conclusions and clinical relevance: Dogs with thymoma, even those with a large tumor burden or a paraneoplastic syndrome, had a good prognosis following surgery. Surgical treatment, tumor stage, and the presence of a second tumor at diagnosis influenced survival time.