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The American Journal of Case Reports Nov 2023BACKGROUND Myasthenia gravis is a neuromuscular disorder that is strongly associated with thymoma. Although the presence of myasthenia gravis with other tumors is...
BACKGROUND Myasthenia gravis is a neuromuscular disorder that is strongly associated with thymoma. Although the presence of myasthenia gravis with other tumors is uncommon, approximately 50% of patients with thymoma have myasthenia gravis. Thymic Hodgkin lymphoma should be considered due to the multiple reported cases of patients with myasthenia gravis and Hodgkin lymphoma. In this report, we present the case of 24-year-old woman with myasthenia gravis who was incidentally found to have coexisting thymoma with thymic Hodgkin lymphoma. CASE REPORT A 24-year-old woman with a known case of vitiligo presented with a 2-year history of diplopia and incidental anterior mediastinal mass. Following investigations, myasthenia gravis was diagnosed and managed by pyridostigmine, prednisolone, and azathioprine. Regarding the anterior mediastinal mass, thymoma was suspected based on the presence of myasthenia gravis and radiological findings. She underwent extended transsternal thymectomy. The final histopathological report of the dissected thymus disclosed Hodgkin lymphoma pathology coexisting with thymoma. After the diagnosis of Hodgkin lymphoma nodular sclerosis type IIA was confirmed, 6 cycles of chemotherapy were administered. Four years of follow-up revealed no evidence of Hodgkin lymphoma. However, her symptoms of myasthenia gravis persisted despite Hodgkin lymphoma remission. CONCLUSIONS There is an unclear association between myasthenia gravies and Hodgkin lymphoma. Prior reports revealed regression of myasthenia gravies following Hodgkin lymphoma management, which suggests that myasthenia could be a complication of Hodgkin lymphoma. However, in our case, myasthenia gravis persisted after Hodgkin lymphoma management; therefore, further studies are needed to explore this association.
Topics: Female; Humans; Young Adult; Hodgkin Disease; Myasthenia Gravis; Pyridostigmine Bromide; Thymoma; Thymus Neoplasms
PubMed: 38006204
DOI: 10.12659/AJCR.941792 -
The Israel Medical Association Journal... Nov 2023
Topics: Humans; Thymoma; Thymus Neoplasms
PubMed: 37980623
DOI: No ID Found -
European Review For Medical and... Nov 2023Thymus is an immune organ in which pathological changes may cause autoimmune diseases, including myasthenia gravis (MG). Recent studies have focused on Toll-like...
OBJECTIVE
Thymus is an immune organ in which pathological changes may cause autoimmune diseases, including myasthenia gravis (MG). Recent studies have focused on Toll-like receptor 4 (TLR4) signaling as the cause of such changes. In our previous study, an imbalance of T helper 17 (Th17) cells and T regulatory (Treg) cells was found in MG thymoma. These results suggest the involvement of TLR4 in the pathogenesis of thymoma MG via an alteration of the Th17/Treg balance. Here, we aimed to assess whether the TLR4-MyD88-NF-κB pathway is upregulated in MG thymoma and its relationship with Th17/Treg cells.
PATIENTS AND METHODS
We collect thymoma samples from 54 patients with or without MG, detecting the expression level of TLR4, MyD88, and NF-κB in thymoma tissues. Next, we established an in vitro experiment of coculturing thymoma cells with CD4+ T cells and detected the differentiation of Th17 cells and Treg cells and their marker protein, retinoid-related orphan receptor gamma t (RORγt) and forkhead transcription factor 3 (Foxp3).
RESULTS
We found TLR4, MyD88, and NF-κB expressed more in MG thymoma compared with simple thymoma. After the transwell coculturing, we observed an imbalance of Th17/Treg cells after TLR4 stimulation.
CONCLUSIONS
TLR4 is stimulated in thymoma, causing an increase of Th17 cells and a decrease of Treg cells, namely an imbalance of Th17/Treg cells, resulting in MG.
Topics: Humans; NF-kappa B; T-Lymphocytes, Regulatory; Thymoma; Myeloid Differentiation Factor 88; Toll-Like Receptor 4; Myasthenia Gravis; Th17 Cells; Thymus Neoplasms; Forkhead Transcription Factors
PubMed: 37975358
DOI: 10.26355/eurrev_202311_34309 -
HCA Healthcare Journal of Medicine 2023Thymomas are a rare form of slow-growing malignancy that originate from thymic epithelial cells presenting as an anterior mediastinal mass. Although most are...
INTRODUCTION
Thymomas are a rare form of slow-growing malignancy that originate from thymic epithelial cells presenting as an anterior mediastinal mass. Although most are asymptomatic, they can have a variety of presentations, such as local thoracic symptoms, superior vena cava syndrome, or paraneoplastic syndromes. Local compressive thoracic symptoms include shortness of breath, chest pain, and cough. Superior vena cava syndrome presents with respiratory, vascular, or neurologic symptoms. Paraneoplastic syndromes, such as myasthenia gravis, are due to abnormal T-cell maturation leading to an increased risk of autoimmune conditions.
CASE PRESENTATION
We report a case of a 71-year-old White male with multiple comorbidities presenting to the emergency room after a mechanical fall with an incidental finding of a 3.8 cm x 6.0 cm anterior mediastinal mass. The patient had no local compressive symptoms or paraneoplastic syndromes. Due to the coronavirus disease 2019 (COVID-19) pandemic, the patient did not follow through with the discharge recommendations for surgical consultation. Over a year later, the patient presented to the emergency room for congestive heart failure exacerbation, and chest computed tomography revealed the mass had increased in size to 8.2 cm x 7.7 cm. A multidisciplinary approach was used to determine the patient's course of treatment. Due to the patient's debilitated state and concern for local invasion, radical thymectomy with mediastinal lymph node dissection was planned. Despite medical optimization and coordination with a multidisciplinary team, following surgery, the patient became symptomatically bradycardic with acute hypoxic respiratory failure. The patient ultimately passed away after pulseless electrical activity and the family's decision to discontinue resuscitation.
CONCLUSION
It is imperative to consider the negative impacts of the COVID-19 pandemic. Delay in treatment allowed the thymoma to rapidly grow, thus leading to a decreased chance for cure. An extensive surgery increased perioperative risks that led to unforeseen complications resulting in the untimely death of the patient.
PubMed: 37969846
DOI: 10.36518/2689-0216.1458 -
Frontiers in Cellular and Infection... 2023The aim of this study is to report an isolated pleural cryptococcosis with pleural effusion as the only manifestation, confirmed by pleural biopsy in a patient with...
OBJECTIVE
The aim of this study is to report an isolated pleural cryptococcosis with pleural effusion as the only manifestation, confirmed by pleural biopsy in a patient with thymoma combined with myasthenia gravis, who developed pleural effusion of unknown origin after long-term glucocorticoids and tacrolimus therapy.
METHODS
Pathological examination of the right pleural biopsy tissue from a patient with unexplained recurrent pleural effusion was implemented. Morphological analysis of the fungal component and metagenomic next-generation sequencing (mNGS) on the pleural tissue were performed.
RESULTS
A biopsy specimen of the right pleura revealed numerous yeast-like organisms surrounded by mucous capsules and neoformans was detected by mNGS with a species-specific read number (SSRN) of 4, confirming the diagnosis of pleural cryptococcosis. Pleural effusion was eliminated with amphotericin B and fluconazole, and healthy status was maintained at the time of review 1 year later.
CONCLUSION
Cryptococcosis, manifested by simple pleural effusion, is extremely rare, but when repeated pleural effusion occurs in immunocompromised patients or in patients with malignant tumors, the possibility of cryptococcosis should be treated with high vigilance and pleural biopsy is recommended if necessary in order to confirm the diagnosis.
Topics: Humans; Pleura; Cryptococcosis; Pleural Effusion; Biopsy; Immunocompromised Host
PubMed: 37953802
DOI: 10.3389/fcimb.2023.1258021 -
Journal of Cardiothoracic Surgery Nov 2023Thymic carcinomas are rare and aggressive tumours. They constitute a heterogeneous group of tumours with various histological patterns and subtypes resembling epithelial...
BACKGROUND
Thymic carcinomas are rare and aggressive tumours. They constitute a heterogeneous group of tumours with various histological patterns and subtypes resembling epithelial tumours arising from other organs.
CASE PRESENTATION
We hereby represent a case of primary thymic carcinoma with adenoid cystic carcinoma-like features (TCACC) which is an extremely rare variant of thymic adenocarcinoma. To date and to the best of our knowledge, there are nine reported cases in literature and ours is the tenth. Our case was treated surgically but the implementation of adjuvant chemoradiotherapy has been reported in few of the published cases.
CONCLUSIONS
TCACC constitutes a rare entity of thymic adenocarcinoma with limited available literature. The current data is derived from few case reports and case series. The histological overlap of these tumours and primary ACC of salivary glands poses a diagnostic challenge. Radiological investigations, immunohistochemical phenotyping and genetic analysis are crucial in establishing the diagnosis.
Topics: Humans; Carcinoma, Adenoid Cystic; Thymus Gland; Adenocarcinoma; Thymoma; Thymus Neoplasms
PubMed: 37946236
DOI: 10.1186/s13019-023-02432-w -
JAMA Network Open Nov 2023Gastrointestinal stromal tumor (GIST) follow-up is recommended by international guidelines, but data on the role of follow-up in patients with low relapse risk are...
IMPORTANCE
Gastrointestinal stromal tumor (GIST) follow-up is recommended by international guidelines, but data on the role of follow-up in patients with low relapse risk are missing. For these patients, the potential benefit of anticipating recurrence detection should be weighed against psychological burden and radiologic examination loads in terms of costs and radiation exposure.
OBJECTIVE
To evaluate the outcomes of guideline-based follow-up in low-risk GIST.
DESIGN, SETTING, AND PARTICIPANTS
This multi-institutional retrospective cohort study involving Italian Sarcoma Group reference institutions evaluated patients with GIST who underwent surgery between January 2001 and June 2019. Median follow-up time was 69.2 months. Data analysis was performed from December 15, 2022, to March 20, 2023. Patients with GIST at low risk according to Armed Forces Institute of Pathology criteria were included provided adequate clinical information was available: primary site, size, mitotic index, surgical margins, and 2 or more years of follow-up.
EXPOSURES
All patients underwent follow-up according to European Society for Medical Oncology (ESMO) guidelines.
MAIN OUTCOMES AND MEASURES
The primary outcome was the number of tests needed to identify a relapse according to ESMO guidelines follow-up plan. Secondary outcomes included relapse rate, relapse timing, disease-free survival (DFS), overall survival (OS), GIST-specific survival (GIST-SS), postrelapse OS, secondary tumor rates, and theoretical ionizing radiation exposure. An exploratory end point, new follow-up schedule proposal for patients with low-risk GIST according to the observed results, was also assessed.
RESULTS
A total of 737 patients (377 men [51.2%]; median age at diagnosis, 63 [range, 18-86] years) with low-risk GIST were included. Estimated 5-year survival rates were 95.5% for DFS, 99.8% for GIST-SS, and 96.1% for OS. Estimated 10-year survival rates were 93.4% for DFS, 98.1% for GIST-SS, and 91.0% for OS. Forty-two patients (5.7%) experienced disease relapse during follow-up (9 local, 31 distant, 2 both), of which 9 were detected after 10 or more years. This translated into approximately 1 relapse detected for every 170 computed tomography scans performed, with a median radiation exposure of 80 (IQR, 32-112) mSv per patient. Nongastric primary tumor (hazard ratio [HR], 2.09; 95% CI, 1.14-3.83; P = .02), and KIT mutation (HR, 2.77; 95% CI, 1.05-7.27; P = .04) were associated with a higher risk of relapse. Second tumors affected 187 of 737 patients (25%), of which 56 were detected during follow-up and represented the primary cause of death in these patients.
CONCLUSIONS AND RELEVANCE
In this cohort study on patients affected by low-risk GISTs, the risk of relapse was low despite a follow-up across 10 or more years. These data suggest the need to revise follow-up schedules to reduce the anxiety, costs, and radiation exposure of currently recommended follow-up strategy.
Topics: Male; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Gastrointestinal Stromal Tumors; Cohort Studies; Follow-Up Studies; Retrospective Studies; Neoplasm Recurrence, Local; Recurrence; Sarcoma; Italy
PubMed: 37930700
DOI: 10.1001/jamanetworkopen.2023.41522 -
Biomedicines Oct 2023Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are... (Review)
Review
BACKGROUND
Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy.
MATERIALS AND METHODS
The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases.
RESULTS
2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8-4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study.
CONCLUSIONS
Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.
PubMed: 37893096
DOI: 10.3390/biomedicines11102722 -
Neurology(R) Neuroimmunology &... Jan 2024Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but come with immune-related adverse events (irAEs) that provide a novel challenge for treating...
OBJECTIVE
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but come with immune-related adverse events (irAEs) that provide a novel challenge for treating physicians. Neuromuscular irAEs, including myositis, myasthenia gravis (MG), and demyelinating polyradiculoneuropathy, lead to significant morbidity and mortality.
METHODS
We present a case of severe myasthenia-myositis-myocarditis overlap in a patient receiving ICIs for breast cancer. Clinical findings were recorded.
RESULTS
A 47-year-old woman developed tetraparesis, dysphagia, and muscle pain during ICI treatment. MG with a thymoma had been diagnosed earlier. Neuromuscular overlap irAEs with cardiac affection was confirmed, and ICI treatment was discontinued. Given a lack of clinical response to standard therapies, a muscle biopsy was performed demonstrating complement deposition. Eculizumab treatment led to rapid improvement in muscle strength and cardiac function.
DISCUSSION
Neuromuscular irAEs are associated with a high in-hospital mortality, and specific treatment strategies remain an unmet need. Here, early muscle biopsy enabled targeted therapy after standard approaches failed, thereby highlighting the value of identifying a specific treatment target. To improve therapeutic outcomes, the development of patient-tailored strategies for neuromuscular irAEs requires further studies.
Topics: Female; Humans; Middle Aged; Immune Checkpoint Inhibitors; Myocarditis; Muscle Weakness; Myasthenia Gravis; Myositis
PubMed: 37884388
DOI: 10.1212/NXI.0000000000200177 -
Journal of Thoracic Disease Sep 2023The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well... (Review)
Review
The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well demonstrated. This is most often described in cases of mesothelioma, thymoma, or other secondary pleural metastases. The utilization of a direct cytotoxic agent with increased penetration secondary to a hyperthermic environment is especially beneficial in pleural malignancy as a microscopic resection remains immensely challenging. Despite favorable outcomes with a limited associated risk profile, there persists a variety in utilization and technique of HITHOC described in current literature. National Comprehensive Cancer Network (NCCN) guidelines state that though intraoperative adjuvant therapies such as HITHOC have been studied, they remain of unclear benefit and definitive recommendations do not currently exist. This ambiguity limits the standardization of HITHOC, thus hindering its further application in a patient population with exceedingly poor outcomes within current guideline-based therapy. As the prevalence of pleural malignancies necessitating CRS with adjuvant HITHOC remains quite low, we believe a task force initiative to further investigate the role of HITHOC in surgical management of pleural malignancies would enable wider utility of this promising technique. Additionally, we propose that the creation of a pleural cancer index could aid in standardization of HITHOC in those with pleural malignancy.
PubMed: 37868886
DOI: 10.21037/jtd-23-454