RESUMEN
Anticytokine autoantibodies are an emerging mechanism of disease in previously healthy adults. Patients with these syndromes demonstrate a unique infectious phenotype associated with neutralizing autoantibodies that target a specific cytokine. Examples include anti-interferon (IFN)-γ autoantibodies and disseminated nontuberculous mycobacteria; anti-granulocyte macrophage colony-stimulating factor autoantibodies and cryptococcal meningitis; anti-interleukin (IL)-6 autoantibodies and staphylococcal skin infection; and anti-IL-17A, anti-IL-17F, or anti-IL-22 autoantibodies and mucocutaneous candidiasis in the setting of either APECED (autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy syndrome) or thymoma. Other anticytokine autoantibodies may contribute to an infectious phenotype such as anti-granulocyte colony stimulating factor and anti-IFN-α autoantibodies, although the strength of the association is less clear. Their identification not only affects disease management but also may uncover key mechanisms of host defense against specific organisms. Furthermore, it raises the possibility that currently idiopathic diseases will someday be explained by a yet unidentified anticytokine autoantibody. This review focuses on the current understanding, both clinical and mechanistic, of anticytokine autoantibody-associated immunodeficiency.
Asunto(s)
Autoanticuerpos/inmunología , Citocinas/inmunología , Síndromes de Inmunodeficiencia/inmunología , Animales , Candidiasis/diagnóstico , Candidiasis/inmunología , Candidiasis/terapia , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/terapia , Poliendocrinopatías Autoinmunes/diagnóstico , Poliendocrinopatías Autoinmunes/inmunología , Poliendocrinopatías Autoinmunes/terapia , Timoma/diagnóstico , Timoma/inmunología , Timoma/terapiaRESUMEN
BACKGROUND: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated Burkholderia gladioli infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation. METHODS: Among the patients (most of whom had thymoma) who were known to have anti-interleukin-12, we screened for autoantibodies against interleukin-23 (anti-interleukin-23). To validate the potential role of anti-interleukin-23 with respect to opportunistic infection, we tested a second cohort of patients with thymoma as well as patients without either thymoma or known anti-interleukin-12 who had unusual infections. RESULTS: Among 30 patients with anti-interleukin-12 who had severe mycobacterial, bacterial, or fungal infections, 15 (50%) also had autoantibodies that neutralized interleukin-23. The potency of such neutralization was correlated with the severity of these infections. The neutralizing activity of anti-interleukin-12 alone was not associated with infection. In the validation cohort of 91 patients with thymoma, the presence of anti-interleukin-23 was associated with infection status in 74 patients (81%). Overall, neutralizing anti-interleukin-23 was detected in 30 of 116 patients (26%) with thymoma and in 30 of 36 patients (83%) with disseminated, cerebral, or pulmonary infections. Anti-interleukin-23 was present in 6 of 32 patients (19%) with severe intracellular infections and in 2 of 16 patients (12%) with unusual intracranial infections, including Cladophialophora bantiana and Mycobacterium avium complex. CONCLUSIONS: Among patients with a variety of mycobacterial, bacterial, or fungal infections, the presence of neutralizing anti-interleukin-23 was associated with severe, persistent opportunistic infections. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
Asunto(s)
Autoanticuerpos , Síndromes de Inmunodeficiencia , Interleucina-23 , Infecciones Oportunistas , Adulto , Humanos , Autoanticuerpos/inmunología , Síndromes de Inmunodeficiencia/inmunología , Interleucina-12/antagonistas & inhibidores , Interleucina-12/inmunología , Interleucina-23/antagonistas & inhibidores , Interleucina-23/inmunología , Micosis/inmunología , Infecciones Oportunistas/inmunología , Timoma/inmunología , Neoplasias del Timo/inmunología , Anticuerpos Neutralizantes/inmunología , Infecciones Bacterianas/inmunologíaRESUMEN
Thymic carcinoma (TC) is a rare malignant tumor with a poor prognosis, and there is currently limited data on the use of immunotherapy in patients with unresectable TC. In this study, data of patients with unresectable TC diagnosed from January 2017 were retrospectively collected from multiple centers. Treatment response, progression-free survival (PFS), overall survival (OS), survival-independent prognostic factor, and adverse events (AEs) were further analyzed. As a result, a total of 93 patients with unresectable TC were enrolled, of which 54 received first-line chemotherapy, and 39 received chemotherapy plus immune checkpoint inhibitors (ICIs). The objective response rate was 50% (27/54) in the chemotherapy group and 76.9% (30/39) in the chemotherapy plus ICIs group. The chemotherapy plus ICIs group achieved significant median PFS benefit (8.8 vs. 34.9 months, p < .001) and median OS benefit (41.8 months vs. not reached, p = .025). Multivariate analysis showed that ICIs and local therapy were independent prognostic factors for PFS. In addition, 17 patients developed immune-related AEs (IRAEs), of which 15 (38.5%) had Grade 1 or 2 IRAEs and 2 (5.1%) had Grade 3 IRAEs in the chemotherapy plus ICIs group. In conclusion, the efficacy of chemotherapy plus ICIs is superior to chemotherapy, and the adverse effects are manageable in patients with unresectable TC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Inhibidores de Puntos de Control Inmunológico , Timoma , Neoplasias del Timo , Humanos , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Anciano , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/mortalidad , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Timoma/tratamiento farmacológico , Timoma/mortalidad , Pronóstico , Supervivencia sin ProgresiónRESUMEN
Ataxia-telangiectasia (A-T) is a rare disorder caused by genetic defects of A-T mutated (ATM) kinase, a key regulator of stress response, and characterized by neurodegeneration, immunodeficiency, and high incidence of cancer. Here we investigated NK cells in a mouse model of A-T (Atm-/-) showing that they are strongly impaired at killing tumor cells due to a block of early signaling events. On the other hand, in Atm-/- littermates with thymic lymphoma NK cell cytotoxicity is enhanced as compared with ATM-proficient mice, possibly via tumor-produced TNF-α. Results also suggest that expansion of exhausted NKG2D+ NK cells in Atm-/- mice is driven by low-level expression of stress-inducible NKG2D ligands, whereas development of thymoma expressing the high-affinity MULT1 ligand is associated with NKG2D down-regulation on NK cells. These results expand our understanding of immunodeficiency in A-T and encourage exploring NK cell biology in A-T patients in the attempt to identify cancer predictive biomarkers and novel therapeutic targets.
Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada , Células Asesinas Naturales , Subfamilia K de Receptores Similares a Lectina de Células NK , Animales , Células Asesinas Naturales/inmunología , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Ratones , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/inmunología , Ratones Noqueados , Ratones Endogámicos C57BL , Timoma/inmunología , Timoma/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/inmunología , Citotoxicidad Inmunológica , Neoplasias del Timo/inmunología , Neoplasias del Timo/genética , Transducción de Señal , Proteínas de la Membrana , Antígenos de Histocompatibilidad Clase IRESUMEN
BACKGROUND: Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome. OBJECTIVES: To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation. METHODS: Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab. RESULTS: Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12-36 months following treatment initiation. CONCLUSION: Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma.
Asunto(s)
Inmunomodulación , Timoma , Humanos , Timoma/inmunología , Timoma/complicaciones , Timoma/diagnóstico , Femenino , Masculino , Rituximab/uso terapéutico , Autoanticuerpos/inmunología , Persona de Mediana Edad , Neoplasias del Timo/inmunología , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Neumonía/etiología , Neumonía/inmunología , Neumonía/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/etiología , Adulto , Azatioprina/uso terapéutico , Linfocitos B/inmunología , Resultado del Tratamiento , Linfocitos T/inmunologíaRESUMEN
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.
Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia , Miastenia Gravis , Células Th17 , Timoma , Femenino , Humanos , Masculino , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Miastenia Gravis/genética , Miastenia Gravis/inmunología , Miastenia Gravis/patología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/inmunología , Células Th17/metabolismo , Células Th17/inmunología , Timoma/complicaciones , Timoma/genética , Timoma/inmunología , Timo/patología , Neoplasias del Timo/complicaciones , Neoplasias del Timo/genéticaRESUMEN
BACKGROUND: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection. METHODS: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis. RESULTS: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 95% confidence interval [CI] 1.010-6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021-1.905; p = 0.036). CONCLUSIONS: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification.
Asunto(s)
Bases de Datos Factuales , Neoplasias Glandulares y Epiteliales , Neoplasias del Timo , Humanos , Neoplasias del Timo/patología , Neoplasias del Timo/cirugía , Neoplasias del Timo/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Glandulares y Epiteliales/mortalidad , Pronóstico , Tasa de Supervivencia , Estudios de Seguimiento , Anciano , Estudios Retrospectivos , Adulto , Estadificación de Neoplasias , Timoma/patología , Timoma/cirugía , Timoma/mortalidad , Pleura/patología , Pleura/cirugía , Invasividad NeoplásicaRESUMEN
The epithelial and lymphoid compartments of the thymus can give rise to a wide variety of tumours, including thymomas, thymic carcinomas, lymphoreticular proliferations, germ cell tumours, and sarcomas. While some of these have close similarity to their counterparts in other organs, both in terms of histology and immunohistochemistry, as well as molecular features, others are unique to the thymus. The epithelial tumours, which can develop in the thymus, will be discussed in this review, with a particular emphasis on resolving differential diagnosis by means of morphology, immunohistochemical profiles, and molecular diagnostics.
Asunto(s)
Neoplasias Glandulares y Epiteliales , Timoma , Neoplasias del Timo , Humanos , Diagnóstico Diferencial , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/patología , Timoma/diagnóstico , Timoma/patología , Neoplasias Glandulares y Epiteliales/diagnósticoRESUMEN
OBJECTIVES: This study aims to develop an innovative, deep model for thymoma risk stratification using preoperative CT images. Current algorithms predominantly focus on radiomic features or 2D deep features and require manual tumor segmentation by radiologists, limiting their practical applicability. METHODS: The deep model was trained and tested on a dataset comprising CT images from 147 patients (82 female; mean age, 54 years ± 10) who underwent surgical resection and received subsequent pathological confirmation. The eligible participants were divided into a training cohort (117 patients) and a testing cohort (30 patients) based on the CT scan time. The model consists of two stages: 3D tumor segmentation and risk stratification. The radiomic model and deep model (2D) were constructed for comparative analysis. Model performance was evaluated through dice coefficient, area under the curve (AUC), and accuracy. RESULTS: In both the training and testing cohorts, the deep model demonstrated better performance in differentiating thymoma risk, boasting AUCs of 0.998 and 0.893 respectively. This was compared to the radiomic model (AUCs of 0.773 and 0.769) and deep model (2D) (AUCs of 0.981 and 0.760). Notably, the deep model was capable of simultaneously identifying lesions, segmenting the region of interest (ROI), and differentiating the risk of thymoma on arterial phase CT images. Its diagnostic prowess outperformed that of the baseline model. CONCLUSIONS: The deep model has the potential to serve as an innovative decision-making tool, assisting on clinical prognosis evaluation and the discernment of suitable treatments for different thymoma pathological subtypes. KEY POINTS: ⢠This study incorporated both tumor segmentation and risk stratification. ⢠The deep model, using clinical and 3D deep features, effectively predicted thymoma risk. ⢠The deep model improved AUCs by 16.1pt and 17.5pt compared to radiomic model and deep model (2D) respectively.
Asunto(s)
Aprendizaje Profundo , Timoma , Neoplasias del Timo , Tomografía Computarizada por Rayos X , Humanos , Femenino , Timoma/diagnóstico por imagen , Timoma/patología , Persona de Mediana Edad , Masculino , Tomografía Computarizada por Rayos X/métodos , Medición de Riesgo/métodos , Neoplasias del Timo/patología , Neoplasias del Timo/diagnóstico por imagen , Adulto , Anciano , Estudios RetrospectivosRESUMEN
OBJECTIVE: The efficacy and safety of subxiphoid thoracoscopic thymectomy (SVATS) for early thymoma are unknown. The purposes of this meta-analysis were to evaluate the effectiveness and safety of SVATS for early thymoma, to compare it with unilateral intercostal approach video thoracoscopic surgery (IVATS) thymectomy, and to investigate the clinical efficacy of modified subxiphoid thoracoscopic thymectomy (MSVATS) for early anterior mediastinal thymoma. METHODS: Original articles describing subxiphoid and unilateral intercostal approaches for thoracoscopic thymectomy to treat early thymoma published up to March 2023 were searched from PubMed, Embase, and the Cochrane Library. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and analyzed for heterogeneity. Clinical data were retrospectively collected from all Masaoka stage I and II thymoma patients who underwent modified subxiphoid and unilateral intercostal approach thoracoscopic thymectomies between September 2020 and March 2023. The operative time, intraoperative bleeding, postoperative drainage, extubation time, postoperative hospital stay, postoperative visual analog pain score (VAS), and postoperative complications were compared, and the clinical advantages of the modified subxiphoid approach for early-stage anterior mediastinal thymoma were analyzed. RESULTS: A total of 1607 cases were included in the seven studies in this paper. Of these, 591 cases underwent SVATS thymectomies, and 1016 cases underwent IVATS thymectomies. SVATS thymectomy was compared with IVATS thymectomy in terms of age (SMD = - 0.09, 95% CI: -0.20 to - 0.03, I2 = 20%, p = 0.13), body mass index (BMI; SMD = - 0.10, 95% CI: -0.21 to - 0.01, I2 = 0%, p = 0.08), thymoma size (SMD = - 0.01, 95% CI: -0.01, I2 = 0%, p = 0.08), operative time (SMD = - 0.70, 95% CI: -1.43-0.03, I2 = 97%, p = 0.06), intraoperative bleeding (SMD = - 0.30. 95% CI: -0.66-0.06, I2 = 89%, p = 0.10), time to extubation (SMD = - 0.34, 95%CI: -0.73-0.05, I2 = 91%, p = 0.09), postoperative hospital stay (SMD = - 0.40, 95% CI: -0.93-0.12, I2 = 93%, p = 0.13), and postoperative complications (odds ratio [OR] = 0.94, 95% CI: 0.42-2.12, I2 = 57%, p = 0.88), which were not statistically significantly different between the SVATS and IVATS groups. However, the postoperative drainage in the SVATS group was less than that in the IVATS group (SMD = - 0.43, 95%CI: -0.84 to - 0.02, I2 = 88%, p = 0.04), and the difference was statistically significant. More importantly, the postoperative VAS was lower in the SVATS group on days 1 (SMD = - 1.73, 95%CI: -2.27 to - 1.19, I2 = 93%, p < 0.00001), 3 (SMD = - 1.88, 95%CI: -2.84 to - 0.81, I2 = 97%, p = 0.0005), and 7 (SMD = - 1.18, 95%CI: -2.28 to - 0.08, I2 = 97%, p = 0.04) than in the IVATS group, and these differences were statistically significant. A total of 117 patients undergoing thoracoscopic thymectomy for early thymoma in the Department of Thoracic Surgery of the Second Hospital of Jilin University were retrospectively collected and included in the analysis, for which a modified subxiphoid approach was used in 42 cases and a unilateral intercostal approach was used in 75 cases. The differences between the two groups (MSVATS vs. IVATS) in general clinical characteristics such as age, sex, tumor diameter, Masaoka stage, Word Health Organization (WHO) stage, and intraoperative and postoperative conditions, including operative time, postoperative drainage, extubation time, postoperative hospital stay, and postoperative complication rates, were not statistically significant (p > 0.05), while BMI, intraoperative bleeding, and VAS on postoperative days 1, 3, and 7 were all statistically significant (p < 0.05) in the MSVATS group compared with the IVATS group. CONCLUSION: The meta-analysis showed that the conventional subxiphoid approach was superior in terms of postoperative drainage and postoperative VAS pain scores compared with the unilateral intercostal approach. Moreover, the modified subxiphoid approach had significant advantages in intraoperative bleeding and postoperative VAS pain scores compared with the unilateral intercostal approach. These results indicate that MSVATS can provide more convenient operation conditions, a better pleural cavity view, and a more complete thymectomy in the treatment of early thymoma, indicating that is a safe and feasible minimally invasive surgical method.
Asunto(s)
Timoma , Neoplasias del Timo , Humanos , Timoma/patología , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/efectos adversos , Cirugía Torácica Asistida por Video/métodos , Neoplasias del Timo/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Dolor Postoperatorio/etiologíaRESUMEN
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.
Asunto(s)
Miastenia Gravis , Timoma , Neoplasias del Timo , Humanos , Timoma/complicaciones , Timoma/cirugía , Estudios Retrospectivos , Timectomía/efectos adversos , Neoplasias del Timo/complicaciones , Neoplasias del Timo/cirugía , Miastenia Gravis/complicacionesRESUMEN
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.
Asunto(s)
Miastenia Gravis , Timoma , Humanos , Femenino , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico , Persona de Mediana Edad , Timoma/complicaciones , Timoma/diagnóstico , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Coristoma/complicaciones , Coristoma/patologíaRESUMEN
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.
Asunto(s)
Alopecia , Miastenia Gravis , Trastornos del Gusto , Humanos , Miastenia Gravis/epidemiología , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico , Alopecia/epidemiología , Alopecia/diagnóstico , Femenino , Masculino , Trastornos del Gusto/epidemiología , Trastornos del Gusto/etiología , Persona de Mediana Edad , Adulto , Anciano , Japón/epidemiología , Sistema de Registros , Timoma/complicaciones , Timoma/epidemiología , IncidenciaRESUMEN
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.
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COVID-19 , Enfermedades de Inmunodeficiencia Primaria , Timoma , Neoplasias del Timo , Masculino , Humanos , Persona de Mediana Edad , SARS-CoV-2/genética , Timoma/complicaciones , Timoma/genética , Irán , GenómicaRESUMEN
Thymic imaging is challenging because the imaging appearance of a variety of benign and malignant thymic conditions are similar. CT is the most commonly used modality for mediastinal imaging, while MRI and fluorine 18 fluorodeoxyglucose (FDG) PET/CT are helpful when they are tailored to the correct indication. Each of these imaging modalities has limitations and technical pitfalls that may lead to an incorrect diagnosis and mismanagement. CT may not be sufficient for the characterization of cystic thymic processes and differentiation between thymic hyperplasia and thymic tumors. MRI can be used to overcome these limitations but is subject to other potential pitfalls such as an equivocal decrease in signal intensity at chemical shift imaging, size limitations, unusual signal intensity for cysts, subtraction artifacts, pseudonodularity on T2-weighted MR images, early imaging misinterpretation, flow and spatial resolution issues hampering assessment of local invasion, and the overlap of apparent diffusion coefficients between malignant and benign thymic entities. FDG PET/CT is not routinely indicated due to some overlap in FDG uptake between thymomas and benign thymic processes. However, it is useful for staging and follow-up of aggressive tumors (eg, thymic carcinoma), particularly for detection of occult metastatic disease. Pitfalls in imaging after treatment of thymic malignancies relate to technical challenges such as postthymectomy sternotomy streak metal artifacts, differentiation of postsurgical thymic bed changes from tumor recurrence, or human error with typical "blind spots" for identification of metastatic disease. Understanding these pitfalls enables appropriate selection of imaging modalities, improves diagnostic accuracy, and guides patient treatment. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.
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Timoma , Neoplasias del Timo , Humanos , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Recurrencia Local de Neoplasia , Neoplasias del Timo/diagnóstico por imagen , Neoplasias del Timo/patología , Timoma/diagnóstico , Tomografía de Emisión de Positrones , Imagen por Resonancia Magnética , RadiofármacosRESUMEN
INTRODUCTION: Surgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis rates subsequent to incomplete or complete resection. Chemoradiotherapy has the potential to induce coronary artery occlusion, thereby potentially impacting patients' long-term survival rates. The existing literature currently lacks comprehensive research on the lesion characteristics of coronary artery injury resulting from chemoradiotherapy. CASE PRESENTATION: The male patient, aged 55, was admitted to the hospital due to recurrent chest tightness and pain persisting for one week. Notably, the patient had previously undergone curative resection surgery for thymic carcinoma seven years ago. After the surgical procedure, the patient underwent a course of adjuvant chemotherapy comprising docetaxel and platinum. 11 months later, imaging examination diagnosed tumor recurrence, and concurrent chemoradiotherapy was administered at a total dose of 62 Gy/31F for planning gross target volume (PGTV) and 54 Gy/31F for planning target volume (PTV) with 2 cycles of paclitaxel and cisplatin. Re-admission of the patient occurred after a 7-year interval subsequent to the completion of concurrent chemoradiotherapy, leading to a subsequent diagnosis of acute non-ST segment elevation myocardial infarction. Following administration of antiplatelet, anticoagulant, and anti-myocardial ischemia therapy, coronary angiography revealed the presence of a bifurcation lesion at the distal end of the left main trunk. Intravascular ultrasound (IVUS) examination demonstrated significant negative remodeling of both the main trunk and its branches at the bifurcation site, characterized by minimal atherosclerotic plaque components. CONCLUSIONS: Chemoradiotherapy may induce damage to endothelial cells, resulting in an inflammatory response. Negative remodeling of blood vessels is likely to occur, primarily characterized by vasoconstriction but with less atherosclerotic plaque burden. Routine stent implantation in negatively remodeled areas may lead to vascular rupture, necessitating intravascular imaging examination.
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Timoma , Neoplasias del Timo , Humanos , Masculino , Neoplasias del Timo/terapia , Neoplasias del Timo/diagnóstico por imagen , Persona de Mediana Edad , Resultado del Tratamiento , Factores de Tiempo , Timoma/terapia , Timoma/diagnóstico por imagen , Angiografía Coronaria , Lesiones del Sistema Vascular/etiología , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/terapia , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/lesiones , Vasos Coronarios/efectos de los fármacos , Quimioradioterapia/efectos adversosRESUMEN
AIM: To develop an aggregate model that integrated clinical data, habitat characteristics, and intratumoral and peritumoral features to assess the risk categorization of thymomas. MATERIALS AND METHODS: We retrospectively analyzed 140 thymoma patients (70 low-risk and 70 high-risk), including pathological data. The patients were randomly divided into training cohort (n = 114) and test cohort (n = 26). The k-means clustering was utilized to partition the primary tumor into habitats based on intratumoral radiomic features, 6 distinct habitats were identified. By expanding the region of interest (ROI) mask, 2 peritumoral regions were obtained. Finally, 7 clinical characteristics, 3 habitat values, 20 radiomic features were utilized to develop an aggregated model, to predict the risk of thymoma. Shapley additive explanations (SHAP) interpretation was used for features importance ranking. The accuracy and area under curve (AUC) were used to analyze the performance of the models. RESULTS: The aggregated model, which utilized the XGBoost classifier, demonstrated the best performance with an AUC of 0.811 and an accuracy of 0.769. In comparison, the radiomic model produced an AUC of 0.654 and an accuracy of 0.692. Additionally, the Intratumoral + peritumoral model exhibited an AUC of 0.728 and an accuracy of 0.769. CONCLUSION: Our study establishes a novel tool to predict the risk of thymoma with a good performance. If prospectively validated, the model may refine thymoma patient selection for risk-adaptative therapy and improve prognosis.
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Timoma , Neoplasias del Timo , Humanos , Masculino , Femenino , Neoplasias del Timo/diagnóstico por imagen , Timoma/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Adulto , Anciano , Tomografía Computarizada por Rayos X/métodosRESUMEN
AIM: To investigate the diagnostic performance of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) for thymic epithelial tumours (TETs) and the complication rate after PTNB including seeding after PTNB. MATERIALS AND METHODS: This retrospective study identified PTNBs for anterior mediastinal lesions between May 2007 and September 2021. The diagnostic performance for TETs and complications were investigated. The concordance of the histological grades of TETs between PTNB and surgery was evaluated. The factors associated with pleural seeding after PTNB were determined using Cox regression analysis. RESULTS: Of 387 PTNBs, 235 PTNBs from 225 patients diagnosed as TETs (124 thymomas and 101 thymic carcinomas) and 150 PTNBs from 133 patients diagnosed as other than TETs were included. The sensitivity, specificity, and accuracy for TETs were 89.4% (210/235), 100% (210/210), and 93.5% (360/385), respectively, with an immediate complication rate of 4.4% (17/385). The concordance rate of the histological grades between PTNB and surgery was 73.3% (77/105) after excluding uncategorised types of thymomas. During follow-up after PTNB (median duration, 38.8 months; range, 0.3-164.6 months), no tract seeding was observed. Pleural seeding was observed in 26 patients. Thymic carcinoma (hazard ratio [HR], 5.94; 95% confidence interval [CI], 2.07-17.08; p=0.001) and incomplete resection (HR, 3.29; 95% CI, 1.20-9.02; p=0.02) were associated with pleural seeding, while the biopsy approach type (transpleural versus parasternal) was not associated (p=0.12). CONCLUSIONS: Pretreatment biopsy for TETs was accurate and safe and may be considered for diagnosing TETs, particularly when the diagnosis is challenging and histological diagnosis is mandatory.
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Neoplasias Glandulares y Epiteliales , Timoma , Neoplasias del Timo , Humanos , Timoma/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Biopsia con Aguja/métodos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Neoplasias del Timo/diagnóstico por imagen , Neoplasias Glandulares y Epiteliales/diagnóstico por imagenRESUMEN
AIM: To explore the value of a radiomics model based on enhanced computed tomography (CT) in differentiating anterior mediastinal lymphoma (AML) and thymoma without myasthenia gravis (MG) and calcification. MATERIALS AND METHODS: The present study analysed patients who were diagnosed histologically with AML and thymoma in three independent institutions. All pre-treatment patients underwent enhanced CT. In the training group of patients from institutions 1 (the First Affiliated Hospital of Kunming Medical University) and 3 (the Yunnan Cancer Hospital), two radiologists independently analysed the enhanced CT images and performed manual segmentation of each tumour. Radiomics features were screened using interobserver interclass coefficient (ICC) analysis, feature correlation analysis, and L1 regularisation. The discriminative efficacy of the logistic regression model was evaluated using receiver operating characteristic (ROC) analysis. Validation group of patients from institution 2 (the Second Affiliated Hospital of Zhejiang University School of Medicine) was used to validate the proposed models. RESULTS: A total of 114 patients were enrolled in this study and 1,743 radiomics features were extracted from the enhanced CT images. After feature screening, the remaining 37 robust radiomics features were used to construct the model. In the training group, the AUC of the model was 0.987 (95% confidence interval [CI]: 0.976-0.999), the sensitivity, specificity, and accuracy were 0.912, 0.946, and 0.924, respectively. In the validation group, the AUC of the model was 0.798 (95% CI: 0.683-0.913), the sensitivity, specificity, and accuracy were 0.760, 0.700, and 0.743, respectively. CONCLUSION: The radiomics model created provided effective information to assist in the selection of clinical strategies, thus reducing unnecessary procedures in patients with AML and guiding direct surgery in patients with thymoma to avoid biopsy.
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Calcinosis , Leucemia Mieloide Aguda , Linfoma , Miastenia Gravis , Timoma , Neoplasias del Timo , Humanos , Timoma/diagnóstico por imagen , Mediastino , Radiómica , China , Neoplasias del Timo/diagnóstico por imagen , Linfoma/diagnóstico por imagen , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Due to the rising demand in cross-sectional thoracic imaging, anterior mediastinal lesions are being identified with increasing frequency. Following iterative and multidisciplinary discussions, the BTOG Thymic Malignancies Special Interest Group have developed an algorithm to standardise the diagnostic approach for these relatively uncommon but important conditions which span from benign (thymic remnant, thymic hyperplasia and thymic cysts) to suspected localised thymomas to suspected more aggressive malignancy (thymic carcinoma, lymphoma and germ cell tumours). For each condition, we provide a brief description, an overview of the key radiological findings and a description of the proposed algorithm including the rationale behind the recommendations. We also highlight the role of magnetic resonance (MR) imaging for the characterisation of anterior mediastinal masses in specific indications when the necessary local resources and expertise exist. In addition, we hope this provides the rationale for service development in MR of the anterior mediastinum where current resource and expertise requires development. Through this standardised pathway, we hope to drive improvements in patient care by rationalising surveillance schedules, avoiding unnecessary resections of benign entities with their associated morbidity and optimising the diagnostic work-up prior to the appropriate treatment of anterior mediastinal malignancies.