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1.
J Neuroinflammation ; 21(1): 126, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734662

RESUMO

Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T (Treg) cells have been demonstrated in subgroups of MG. On the other hand, hypoxia-inducible factor 1 (HIF-1) has been shown to regulate the Th17/Treg balance by inducing Th17 differentiation while attenuating Treg development. To identify the underlying mechanisms of different thymic pathologies in MG development, we evaluated thymic samples from thymoma-associated myasthenia gravis (TAMG), MG with hyperplasia (TFH-MG) and thymoma without MG (TOMA) patients. Differential gene expression analysis revealed that TAMG and TFH-MG cells are associated with different functional pathways. A higher RORC/FOXP3 ratio provided evidence for Th17/Treg imbalance in TAMG potentially related to increased HIF1A. The hypoxic microenvironment in thymoma may be a driver of TAMG by increasing HIF1A. These findings may lead to new therapeutic approaches targeting HIF1A in the development of TAMG.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Miastenia Gravis , Linfócitos T Reguladores , Células Th17 , Timoma , Timo , Neoplasias do Timo , Miastenia Gravis/genética , Miastenia Gravis/imunologia , Miastenia Gravis/patologia , Timoma/complicações , Timoma/genética , Timoma/imunologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/imunologia , Células Th17/metabolismo , Células Th17/imunologia , Timo/patologia , Masculino , Feminino , Neoplasias do Timo/complicações , Neoplasias do Timo/genética , Adulto , Pessoa de Meia-Idade , Idoso
2.
Neurology ; 102(12): e209482, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38781559

RESUMO

The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the development of autoimmune diseases and cancer. Recently, a concern has been raised about deleterious consequences of the surgical removal of thymic tissue, including for patients who undergo thymectomy for myasthenia gravis (MG) or resection of a thymoma. This review adopts a multidisciplinary approach to scrutinize the evidence concerning the long-term risks of cancer and autoimmunity postthymectomy. We conclude that for patients with acetylcholine receptor antibody-positive MG and those diagnosed with thymoma, the removal of the thymus offers prominent benefits that well outweigh the potential risks. However, incidental removal of thymic tissue during other thoracic surgeries should be minimized whenever feasible.


Assuntos
Miastenia Gravis , Timectomia , Timoma , Timo , Neoplasias do Timo , Humanos , Timectomia/efeitos adversos , Timectomia/métodos , Miastenia Gravis/cirurgia , Timo/cirurgia , Neoplasias do Timo/cirurgia , Neoplasias do Timo/complicações , Timoma/cirurgia , Timoma/complicações , Complicações Pós-Operatórias/etiologia , Doenças Autoimunes/cirurgia
3.
BMC Neurol ; 24(1): 173, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783232

RESUMO

BACKGROUND: Ectopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG). CASE PRESENTATION: We report a case of myasthenia gravis with an ectopic thymoma in the neck, whose myasthenic symptoms significantly improved after complete removal of the mass. A 55-year-old woman with generalized myasthenia gravis (MG) experienced worsening neuromuscular weakness after abruptly discontinuing pyridostigmine. Testing revealed acetylcholine receptor-antibody (AChR-Ab) positivity and a cervical mass initially thought to be thyroid or parathyroid was identified as a thymoma, type A. Post-surgery and radiation therapy, her myasthenic symptoms improved significantly with less prednisone and pyridostigmine requirements over time and no need for additional immunotherapies. CONCLUSIONS: Diagnosing ECTs is challenging due to rarity, atypical locations, and inconclusive fine needle aspiration cytology (FNAC) results, often misinterpreted as thyroid or parathyroid lesions. As proper management of patients with MG, including thymectomy, offers favorable clinical outcomes such as significant improvement in myasthenic complaints and reduced immunosuppressive medication requirements, clinicians should be vigilant of the ectopic locations of thymomas to ensure timely diagnosis and intervention.


Assuntos
Miastenia Gravis , Timoma , Humanos , Feminino , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Pessoa de Meia-Idade , Timoma/complicações , Timoma/diagnóstico , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Coristoma/complicações , Coristoma/patologia
4.
Int J Rheum Dis ; 27(5): e15187, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38742741

RESUMO

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.


Assuntos
Artrite , Miosite , Síndromes Paraneoplásicas , Timoma , Neoplasias do Timo , Humanos , Masculino , Miosite/diagnóstico , Miosite/complicações , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Adolescente , Artrite/diagnóstico , Artrite/etiologia , Timoma/complicações , Timoma/diagnóstico , Resultado do Tratamento , Timectomia , Biópsia
5.
Kyobu Geka ; 77(5): 394-398, 2024 May.
Artigo em Japonês | MEDLINE | ID: mdl-38720610

RESUMO

A 73-year-old woman presented with left anterior chest pain and back pain. Computed tomography (CT) scan showed an anterior mediastinal tumor. It also showed partial anomalous pulmonary venous drainage (left superior pulmonary vein draining into the left brachiocephalic vein), and the tumor was located near the left brachiocephalic vein. The operation was performed through a median sternotomy to resect the thymus and tumor with partial resection of the left upper lobe due to the tumor's adhesion to the left upper lobe. One of the vascular anomalies encountered in adult thoracic surgery is partial anomalous pulmonary venous drainage. It is important to recognize the presence of such an anomaly on imaging and to anticipate the surgical procedure with a preoperative surgical technique.


Assuntos
Veias Pulmonares , Timoma , Neoplasias do Timo , Tomografia Computadorizada por Raios X , Humanos , Feminino , Idoso , Veias Pulmonares/anormalidades , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Timoma/cirurgia , Timoma/diagnóstico por imagem , Timoma/complicações , Neoplasias do Timo/cirurgia , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/complicações
6.
BMC Neurol ; 24(1): 139, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664714

RESUMO

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.


Assuntos
Alopecia , Miastenia Gravis , Distúrbios do Paladar , Humanos , Miastenia Gravis/epidemiologia , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Alopecia/epidemiologia , Alopecia/diagnóstico , Feminino , Masculino , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/etiologia , Pessoa de Meia-Idade , Adulto , Idoso , Japão/epidemiologia , Sistema de Registros , Timoma/complicações , Timoma/epidemiologia , Incidência
7.
Handb Clin Neurol ; 200: 385-396, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494291

RESUMO

Thymoma is often associated with paraneoplastic neurologic diseases. Neural autoantibody testing is an important tool aiding diagnosis of thymoma and its autoimmune neurologic complications. Autoantibodies specific for muscle striational antigens and ion channels of the ligand-gated nicotinic acetylcholine receptor superfamily are the most prevalent biomarkers. The autoimmune neurologic disorders associating most commonly with thymoma are myasthenia gravis (MG), peripheral nerve hyperexcitability (neuromyotonia and Morvan syndrome), dysautonomia, and encephalitis. Patients presenting with these neurologic disorders should be screened for thymoma at diagnosis. Although they can cause profound disability, they usually respond to immunotherapy and treatment of the thymoma. Worsening of the neurologic disorder following surgical removal of a thymoma may herald tumor recurrence. Prompt recognition of paraneoplastic neurologic disorders is critical for patient management. A multidisciplinary approach is required for optimal management of neurologic autoimmunity associated with thymoma.


Assuntos
Síndrome de Isaacs , Doenças do Sistema Nervoso , Timoma , Neoplasias do Timo , Humanos , Timoma/complicações , Timoma/diagnóstico , Recidiva Local de Neoplasia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Autoanticorpos , Doenças do Sistema Nervoso/complicações
8.
BMC Infect Dis ; 24(1): 216, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373941

RESUMO

The coronavirus disease of 2019 (COVID-19) resulted from an infection by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) which is the main cause of acute respiratory distress syndrome (ARDS) in global population from 2019 on. It may contribute to higher rate of death among the patients with immunodeficiency based on recent reports. In addition, Good syndrome (GS) as a result of thymoma removal might cause in some long-lasting microbial infections. We described clinical aspects and viral mutations on a case of GS suffering from COVID-19. A 46-year-old man with fever, common respiratory disease symptoms and positive COVID-19 polymerase chain reaction (PCR) test, with the history of thymoma removal surgery was admitted to Masih Daneshvari Hospital, Tehran, Iran. Lung radiographs and oxygen saturation measurement disclosed considerable implication resulted in application of several anti-microbial medication. The delta variant (B.1.617.2 (21 J Clade)) was the strain isolated from the patient by sequencing methods done by the COVID-19 National Reference Laboratory (CNRL), Pasteur Institute of Iran, while the dominant strain circulated mostly among population was Omicron (B.1.1.529) at the time of sampling. Unfortunately, the patient had passed away a month later by sudden respiratory failure progressed in refractory septic shock. Despite the fact that opportunistic infections may lead the GS patients to a major health problematic condition, unusual persistent of infections such as non-dominant variant of SARS-Cov-2 could be observed through the disease timeline. Therefore, a fully screening of thymoma plus intra-host evolution monitoring of SARS-CoV-2 is highly recommended in immunocompromised patients.


Assuntos
COVID-19 , Doenças da Imunodeficiência Primária , Timoma , Neoplasias do Timo , Masculino , Humanos , Pessoa de Meia-Idade , SARS-CoV-2/genética , Timoma/complicações , Timoma/genética , Irã (Geográfico) , Genômica
9.
CNS Neurosci Ther ; 30(2): e14568, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38421083

RESUMO

OBJECTIVES: This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics. METHODS: Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022. RESULTS: A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence. CONCLUSIONS: There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.


Assuntos
Encefalite , Doença de Hashimoto , Miastenia Gravis , Timoma , Neoplasias do Timo , Humanos , Timoma/complicações , Timoma/diagnóstico , Timoma/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/cirurgia , Miastenia Gravis/complicações , Miastenia Gravis/terapia , Encefalite/terapia , Encefalite/complicações
10.
BMC Nephrol ; 25(1): 53, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336671

RESUMO

BACKGROUND: Minimal change nephrotic syndrome (MCNS) can be complicated by thymoma; however, no standard therapy for thymoma-associated MCNS has yet been established. We herein describe a case of steroid-resistant MCNS associated with thymoma, treated effectively with rituximab. CASE PRESENTATION: A 71-year-old Japanese man was referred to our department with severe proteinuria (20 g/gCr). Renal biopsy showed minimal change disease and computed tomography revealed an anterior mediastinal mass. Based on these findings, he was diagnosed with thymoma-associated MCNS. He was treated with oral prednisolone (50 mg/day) and cyclosporine, and underwent thymectomy and plasma exchange. However, no improvement in proteinuria was observed. He therefore received intravenous rituximab 500 mg, resulting in a marked decrease in proteinuria from 5328 to 336 mg/day after 1 week. CONCLUSIONS: This case suggests that rituximab might be an effective therapy in patients with steroid-resistant MCNS associated with thymoma.


Assuntos
Nefrose Lipoide , Síndrome Nefrótica , Timoma , Neoplasias do Timo , Masculino , Humanos , Idoso , Timoma/complicações , Timoma/diagnóstico por imagem , Timoma/tratamento farmacológico , Ciclosporina/uso terapêutico , Nefrose Lipoide/complicações , Nefrose Lipoide/tratamento farmacológico , Rituximab/uso terapêutico , Timectomia/efeitos adversos , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia , Síndrome Nefrótica/complicações , Prednisolona , Proteinúria/etiologia
11.
Sci Rep ; 14(1): 2674, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302676

RESUMO

B-cell subsets in peripheral blood (PB) and tumor microenvironment (TME) were evaluated to determine myasthenia gravis (MG) severity in patients with thymoma-associated MG (TMG) and the distribution of B cells in type B TMG. The distribution of mature B cells, including Bm1-Bm5, CD19+ and CD20+ B cells and non-switched (NSMBCs) and switched (SMBCs) memory B cells, were determined in 79 patients with thymoma or TMG. Quantitative relationships between the T and TMG groups and the TMG-low and TMG-high subgroups were determined. NSMBCs and SMBCs were compared in TME and PB. Type B thymoma was more likely to develop into MG, with types B2 and B3 being especially associated with MG worsening. The percentage of CD19+ B cells in PB gradually increased, whereas the percentage of CD20+ B cells and the CD19/CD20 ratio were not altered. The (Bm2 + Bm2')/(eBm5 + Bm5) index was significantly higher in the TMG-high than in thymoma group. The difference between SMBC/CD19+ and NSMBC/CD19+ B cell ratios was significantly lower in the thymoma than TMG group. NSMBCs assembled around tertiary lymphoid tissue in thymomas of patients with TMG. Few NSMBCs were observed in patients with thymoma alone, with these cells being diffusely distributed. MG severity in patients with TMG can be determined by measuring CD19+ B cells and Bm1-Bm5 in PB. The CD19/CD20 ratio is a marker of disease severity in TMG patients. Differences between NSMBCs and SMBCs in PB and TME of thymomas can synergistically determine MG severity in patients with TMG.


Assuntos
Subpopulações de Linfócitos B , Miastenia Gravis , Timoma , Neoplasias do Timo , Humanos , Timoma/complicações , Timoma/patologia , Subpopulações de Linfócitos B/patologia , Neoplasias do Timo/complicações , Neoplasias do Timo/patologia , Linfócitos B/patologia , Miastenia Gravis/complicações , Microambiente Tumoral
12.
Surv Ophthalmol ; 69(3): 418-426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38176471

RESUMO

Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome. Only18 cases of CMVR have been described, most of them unilateral with poor visual outcomes. We discuss the clinical features of CMVR in patients with reported GS, pathogenesis, and outline a work-up for diagnosis. CMVR in an apparently healthy patient should encourage the clinician to search for human immunodeficiency virus (HIV) and non-HIV-associated immunosuppression.


Assuntos
Agamaglobulinemia , Retinite por Citomegalovirus , Timoma , Humanos , Retinite por Citomegalovirus/diagnóstico , Retinite por Citomegalovirus/tratamento farmacológico , Timoma/complicações , Timoma/diagnóstico , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/complicações , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico
13.
Ann Clin Transl Neurol ; 11(3): 710-718, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38251800

RESUMO

BACKGROUND: We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic disorders (PND). METHODS: This is a retrospective study of patients with CV2/CRMP5-IgG PND evaluated between 2002-2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan-Meier estimates were used to determine the probability of survival. RESULTS: Twenty-seven patients (56% female) with CV2/CRMP5-IgG PND were identified with a median follow-up of 54 months (IQR = 11-102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow-up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87-30.64, P = 0.005). Moderate-severe mRS = 3-5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18-41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55-93.04, P < 0.001) was significantly associated with mortality, while thymoma was not. INTERPRETATION: In this retrospective longitudinal study of CV2/CRMP5-IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population.


Assuntos
Ataxia Cerebelar , Neoplasias Pulmonares , Doenças do Sistema Nervoso , Carcinoma de Pequenas Células do Pulmão , Doenças da Medula Espinal , Timoma , Neoplasias do Timo , Humanos , Feminino , Masculino , Estudos Retrospectivos , Proteínas do Tecido Nervoso , Proteínas Associadas aos Microtúbulos , Estudos Longitudinais , Autoanticorpos , Doenças do Sistema Nervoso/etiologia , Timoma/complicações , Neoplasias do Timo/complicações , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Imunoglobulina G
14.
Medicine (Baltimore) ; 103(3): e36920, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38241556

RESUMO

RATIONALE: Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage. PATIENT CONCERNS: We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0.1 × 109/L. The bone marrow aspirates showed decreased granulocyte proliferation. Computed tomography showed a large mass in the anterior mediastinum. DIAGNOSES: The final diagnosis of our patient was PWCA and thymoma. INTERVENTIONS: She underwent a thymectomy and cyclosporine A administration during first remission. OUTCOMES: Long-term remission was achieved following the readministration of cyclosporine A after the disease recurrence. LESSONS: PWCA or agranulocytosis with thymoma has been confirmed to be an extremely rare disease. Thymomas with PWCA correlate with autoimmunity. From this case study and the literature review, we concluded that the pathogenesis of thymomas in PWCA is mainly related to the activation of autoreactive T cells. Thymectomy and the immunosuppressive drug, cyclosporine A, were chosen for treatment. The patient's granulocyte levels were unable to recover after surgery because of the inability to promptly clear activated T cells. After surgery, cyclosporine A continued to take for a long time. Thymectomy combined with prolonged cyclosporine A administration may be an effective method for treating this rare disease.


Assuntos
Agranulocitose , Timoma , Neoplasias do Timo , Humanos , Feminino , Idoso , Timoma/complicações , Timoma/diagnóstico , Timoma/cirurgia , Ciclosporina/uso terapêutico , Timectomia , Doenças Raras , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/cirurgia , Agranulocitose/tratamento farmacológico
15.
JAMA Dermatol ; 160(2): 224-225, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38170503

RESUMO

A woman in her 30s with myasthenia gravis diagnosed at age 27 years presented to the emergency department with severe erythroderma over the past 2 months. What is your diagnosis?


Assuntos
Dermatite Esfoliativa , Miastenia Gravis , Timoma , Neoplasias do Timo , Humanos , Timoma/complicações , Timoma/diagnóstico , Dermatite Esfoliativa/diagnóstico , Dermatite Esfoliativa/etiologia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico
16.
J Cardiothorac Surg ; 19(1): 37, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297367

RESUMO

BACKGROUND: Thymoma and myasthenia gravis (MG) interact with each other. This study aimed to evaluate the effects of thymoma on neurological outcome of MG patients after thymectomy using the propensity score matching (PSM) method. METHODS: Consecutive patients with MG who underwent thymectomy at Beijing Hospital between January 2012 and August 2021 were retrospectively enrolled. Clinical and follow-up data were collected. Statistical analysis was performed using SPSS 23.0 software. PSM was performed to eliminate selection bias. RESULTS: A total of 456 patients were included in this study. Thymoma was present in 138 (30.3%) patients. The median follow-up time was 72 (range, 12-135) months. At the last follow-up, a lower proportion of thymomatous MG patients achieved complete stable remission (CSR) compared with non-thymomatous MG patients (P = 0.011), and the effective rate [CSR + pharmatologic remission (PR) + minimal manifestations (MM)] of thymomatous MG patients was also lower (P = 0.037). Considering time to CSR, Kaplan-Meier analysis showed thymomatous MG patients had lower cumulative CSR rate than non-thymomatous MG patients (log-rank, P = 0.019). After PSM, 105 pairs of patients were matched successfully. For the matched patients, thymomatous MG patients had a lower CSR rate and a lower effective rate (P = 0.002, 0.039, respectively), and K-M analysis still showed thymomatous MG patients had lower cumulative CSR rate (log-rank, P = 0.048). Multivariate Cox analysis demonstrated that thymoma (HR: 0.592, 95% CI 0.389-0.900, P = 0.014), older age at the time of surgery (HR: 0.971, 95% CI 0.953-0.990, P = 0.003), and preoperative course of MG > 12 months (HR: 0.474, 95% CI 0.317-0.708, P = 0.000) were negative predictive factors for CSR. CONCLUSIONS: Thymoma had a negative effect on the neurological outcome of MG after thymectomy. MG patients with old age and a preoperative course of longer than one year had a lower probability of achieving CSR.


Assuntos
Miastenia Gravis , Timoma , Neoplasias do Timo , Humanos , Timoma/complicações , Timoma/cirurgia , Timectomia/métodos , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia , Miastenia Gravis/complicações , Miastenia Gravis/cirurgia , Resposta Patológica Completa , Resultado do Tratamento
17.
Int J Surg Pathol ; 32(1): 155-159, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37093756

RESUMO

Thymomas are tumors of the mediastinum often associated with autoimmune conditions, in particular myasthenia gravis. In contrast, among the fewer than 40 reports of metaplastic thymoma, myasthenia gravis is rarely found. We describe the fourth patient, and first man, with metaplastic thymoma and myasthenia gravis. A 34-year-old had acute onset of double vision with associated dysphagia and was found to have an elevation of serum acetylcholine receptor antibodies. He underwent a transsternal thymectomy. Tissue sections showed a biphasic proliferation of keratin-positive epithelial cells with a complement of spindle cells confirming the diagnosis of metaplastic thymoma. Terminal deoxynucleotidyl transferase (TDT)-positive T lymphocytes were rare and only found in the periphery of the tumor, consistent with thymic remnant. A YAP1::MAML2 gene fusion, with an in-frame fusion between genes YAP1 Exon5 (NM_001130145) and MAML2 Exon2 (NM_032427) was found, supporting further the diagnosis of metaplastic thymoma (Anchored multiplex RNA sequencing [Archer Dx, Boulder, CO] assay). The patient's gender and relatively young age, the presence of an autoimmune condition, and the lack of lymphocytic infiltrate all contribute unusual features to this case and suggest avenues for further exploration.


Assuntos
Miastenia Gravis , Timoma , Neoplasias do Timo , Masculino , Humanos , Adulto , Timoma/complicações , Timoma/diagnóstico , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Linfócitos T , Timectomia
18.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 817-828, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37498332

RESUMO

Clinically, thymoma patients are often complicated with myasthenia gravis (MG). Dexamethasone, a glucocorticoid with anti-inflammatory effects, could be used as an immunosuppressant for thymoma-associated MG, but the mechanism of action remains to be explored. In this study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, weighted gene co-expression network analysis (WGCNA) of potential targets was performed by screening the intersection targets of dexamethasone and thymoma-associated MG from the database. Furthermore, the key targets and core active components were identified by topological analysis of the protein-protein interaction (PPI) network. Molecular docking technology was applied to screen the complexes with stable binding of dexamethasone and core targets. Patients with thymoma were divided into two groups according to whether they received dexamethasone before operation, and immunohistochemistry and western blot were used to verify the selected target of dexamethasone in treating thymoma-associated MG. The results showed that the action pathway of dexamethasone on the disease was closely enriched to phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR) signaling pathways. The expressions of AKT1 and its downstream molecule mTOR in the thymoma microenvironment of thymoma-associated MG patients who did not receive dexamethasone before operation were higher than those in the group receiving dexamethasone before operation. This study demonstrates that dexamethasone can promote apoptosis through the AKT-mTOR pathway for the treatment of thymoma-associated MG, as validated by network pharmacology predictions and clinical specimen experiments, and can be verified by large-scale clinical trials in the future. This study also provides theoretical support and new research perspectives for this disease.


Assuntos
Timoma , Neoplasias do Timo , Humanos , Timoma/complicações , Timoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Serina-Treonina Quinases TOR , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Microambiente Tumoral
19.
Eur J Neurol ; 31(2): e16119, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37909803

RESUMO

BACKGROUND AND PURPOSE: Germinal centers (GCs) can be observed in the thymic tissues of patients with thymoma-associated myasthenia gravis (MG). Although an association between thymic GCs and MG has been suggested, it is unknown whether the presence of GCs could predict the development of MG after the resection of thymoma, known as postthymectomy MG. METHODS: We conducted a retrospective analysis of previously nonmyasthenic patients who underwent surgical removal of the thymoma. All available thymic tissue slides were rereviewed by a pathologist to assess for GCs. Patients were classified into GC-positive and GC-negative groups based on the presence of GCs. The incidence of postthymectomy MG was compared between the two groups, and the risk factors for postthymectomy MG were assessed. RESULTS: Of the 196 previously nonmyasthenic patients who underwent thymoma resection, 21 were GC-positive, whereas 175 were GC-negative. Postthymectomy MG developed in 11 (5.6%) patients and showed a higher incidence in the GC-positive group than in the GC-negative group (33.3% vs. 2.3%, p < 0.001). No postoperative radiotherapy and the presence of GCs were risk factors for postthymectomy MG in the univariate analysis. In multivariate analysis, invasive thymoma (hazard ratio [HR] = 9.835, 95% confidence interval [CI] = 1.358-105.372), postoperative radiotherapy (HR = 0.160, 95% CI = 0.029-0.893), and presence of GCs (HR = 15.834, 95% CI = 3.742-67.000) were significantly associated with postthymectomy MG. CONCLUSIONS: Thymic GCs may be a significant risk factor for postthymectomy MG. Even in patients with thymoma who do not show clinical symptoms of MG, postthymectomy MG should be considered, especially if thymic GCs are observed.


Assuntos
Miastenia Gravis , Timoma , Neoplasias do Timo , Humanos , Timoma/complicações , Timoma/cirurgia , Estudos Retrospectivos , Timectomia/efeitos adversos , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia , Miastenia Gravis/complicações
20.
Neurol Sci ; 45(5): 2203-2209, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38051411

RESUMO

Association between anti-GABAAR encephalitis and myasthenia gravis is extremely rare with few reported cases. Herein, we report a case of a female patient diagnosed with anti-GABAAR encephalitis and thymoma at the first admission. She was administered glucocorticoids for long-term immunotherapy, and thymectomy with biopsy demonstrated a type A thymoma. After 4 months, the symptoms of encephalitis were relieved, but she then developed post-thymectomy myasthenia gravis with anti-AChR and anti-titin dual positivity. Antibodies to connective tissue (anti-ANA, anti-PCNA) and those characteristics of paraneoplastic syndrome (anti-Ma2/Ta) were also positive. She received oral glucocorticoids and tacrolimus as immunosuppressive therapy, and myasthenic symptoms were stable during a 2-year follow-up. Our case revealed that anti-GABAAR encephalitis and myasthenia gravis can appear in patient with type A thymoma at different periods, which alerts physicians to take long-term follow-up for anti-GABAAR encephalitis with thymoma, even after thymectomy. Concurrent positivity for more than one antibody after thymectomy is rarely observed, and their contribution to the clinical course and treatment decision remains to be further investigated.


Assuntos
Encefalite , Miastenia Gravis , Timoma , Neoplasias do Timo , Feminino , Humanos , Timoma/complicações , Timoma/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia , Miastenia Gravis/diagnóstico , Anticorpos , Glucocorticoides , Timectomia
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