Thymoma Research Articles

Sequential development of diffuse panbronchiolitis and myasthenia gravis after thymectomy for thymic neoplasm: a case report

BackgroundMyasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. Only three cases of combined MG and DPB have been reported in the literature.Case presentationA 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. She had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Chest computed tomography scan revealed diffuse bronchitis and bronchiolitis. DPB was confirmed after video-assisted thoracoscopic surgery lung biopsy, and repeated sputum cultures grew Pseudomonas aeruginosa. She has been on long-term oral azithromycin therapy thereafter. Intravenous antipseudomonal antibiotics, inhaled amikacin, as well as oral levofloxacin were administered. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Her muscle weakness gradually improved after pyridostigmine and corticosteroid therapies. Oral corticosteroids could be tapered off ten months after the diagnosis of MG. She is currently maintained on azithromycin, pyridostigmine, and inhaled amikacin therapies, with intravenous antibiotics administered occasionally during hospitalizations for respiratory infections.ConclusionsTo our knowledge, this might be the first case report of sequential development of DPB followed by PTMG. The coexistence of these two disorders poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapies for MG.

Weighted gene coexpression network analysis and machine learning for the determination of tfh cell and B cell infiltrating biomarkers in thymoma-associated myasthenia gravis

Patients with thymoma (THYM)-associated myasthenia gravis (MG) typically have a poor prognosis and recurring illness. This study aimed to discover important biomarkers associated with immune cell infiltration and THYM-associated MG (THYM-MG) development. Gene expression microarray data were downloaded from The Cancer Genome Atlas website (TCGA) and Gene Expression Omnibus (GEO). A total of 102 differentially expressed genes were investigated. According to the immune infiltration data, the distribution of Tfh cells, B cells, and CD4 T cells differed significantly between the THYM-MG and THYM-NMG groups. WGCNA derived 25 coexpression modules; one hub module (the blue module) strongly correlated with Tfh cells. Combining differential genes revealed 21 intersecting genes. LASSO analysis subsequently revealed 16 hub genes as potential THYM-MG biomarkers. ROC curve analysis of the predictive model revealed moderate diagnostic value. The association between the 16 hub genes and infiltrating immune cells was further evaluated in TIMER2.0 and the validation dataset. Draggability analysis identified the therapeutic target genes PTGS2 and ALB, along with significant drugs including Firocoxib, Alclofenac, Pyridostigmine, and Stavudine. This was validated through MD simulation, PCA, and MM-GBSA analyses. The interaction between numerous activated B cells and follicular helper T cells is closely associated with THYM-MG pathogenesis from a bioinformatics perspective. Hub genes (including SP6, SCUBE3, B3GNT7, and MAGEL2) may be downregulated in immune cells in THYM-MG and associated with progression.

OTP Expression in Pulmonary and Thymic Neuroendocrine Neoplasms.

OTP Expression in Pulmonary and Thymic Neuroendocrine Neoplasms.

Primary glomus tumor of the thymus in a 66-year-old patient

We report a unique case of a 66-year-old man who was incidentally identified to have a mass in the thymus region by computerized tomography scan. CT revealed a well-defined 1.6 × 1 × 0.9 cm thymus mass with moderate uniform enhancement. Thoracoscopic thymectomy was performed, and the pathological diagnosis was primary glomus tumor of the thymus. There were no atypia or malignant histological features, and no primary tumors in other sites. To our knowledge, this is the first case of primary thymic glomus tumor reported in the literature.

Updated Outcomes of Surgical Treatment for Recurrent Thymic Tumor: A Report from the Japanese Nationwide Database.

This study aimed to analyze the surgical outcomes for recurrent thymic epithelial tumors and identify the factors associated with post-recurrence survival, using an updated Japanese nationwide database. The cohort that developed recurrence after the initial resection was extracted from an updated database of patients whose thymic epithelial tumors were treated surgically between 1991 and 2010. Furthermore, we reviewed clinicopathological and prognostic factors of re-resected cases. Post-recurrence survival outcomes and cause-specific deaths in non-re-resected cases were also reviewed. We enrolled 191 patients who underwent re-resection and 259 patients who did not. In the surgery group, more patients with early-stage disease, less aggressive World Health Organization (WHO) histological classification, initial complete resection, and shorter recurrence-free intervals were included. Non-thymic carcinoma, absence of preoperative treatment, longer recurrent-free interval, single-site recurrence, and R0-1 re-resection were all significantly favourable prognostic factors for post-recurrence survival in the surgery group, according to univariable analyses. Non-thymic carcinoma histology, longer recurrence-free interval, and R0-1 re-resection were identified as independent prognostic factors according to multivariable analysis. The post-recurrence survival of the entire cohort with R2 re-resection was significantly better than that of the non-surgery group, although it was not demonstrated that patients with thymoma who underwent R2 re-resection had significantly better post-recurrence and lower cause-specific death. R0-1 re-resection was newly identified as a prognostic factor after re-resection, in addition to non-thymic carcinoma histological classification and longer recurrence-free intervals, as documented in the initial report.

Tislelizumab combined with chemotherapy in advanced thymic tumors.

e20139 Background: Thymic tumors refer to tumors derived from thymic epithelial cells, including thymoma and thymic carcinoma. Most cases in advanced stages when detected, and treatment is still controversial. Since 2018, immunotherapy has gradually been used for a variety of solid tumors and the curative efficacy has been notable. The efficacy of immunotherapy is increasingly improved with the increased expression of programmed death-ligand 1 (PD-L1) by tumor cells. The thymus is an immune-rich organ. PD-L1 expression ranges from 23% to 92% in thymoma, and from 36% to 100% in thymic carcinoma. Thus, immunotherapy has been implicated as having broad prospects in the treatment of thymic tumors. Tislelizumab is an inhibitor of PD-1, which has shown preliminary anti-tumor effects in various solid tumors. The combination of immunotherapy and chemotherapy has produced excellent anti-tumor activity for various types of tumors. However, there is a lack of clinical trial data to support the application of tislelizumab for the treatment of advanced thymic tumors. In this article, the efficacy and safety of tislelizumab combined with chemotherapy were analyzed in eight patients with advanced thymic tumors to provide data for the use of this monoclonal antibody as first-line treatment of advanced thymic tumors. Methods: Here, after obtaining fully informed consent, we report cases involving eight patients with advanced thymic tumors treated with tislelizumab combined with chemotherapy. The clinical characteristics, lesion changes, treatment process, drugs used, drug efficacy, complications or adverse reactions were recorded and followed up to evaluate the efficacy and safety of tislelizumab combined with chemotherapy in the treatment of advanced thymic tumors. Results: This article reports eight cases of advanced thymic tumor treated with tislelizumab combined with chemotherapy. Two patients received tislelizumab combined with chemotherapy as first-line treatment, and the remaining six patients were treated with tislelizumab after poor response to chemotherapy. Five patients achieved a partial response to the combined treatment. Of these, the partial response was retained in three patients after switching to tislelizumab monotherapy. The remaining three patients displayed stable disease after the combined treatment. There were no serious immune-related adverse events during treatment. The side effects of tislelizumab combined with chemotherapy were well tolerated. Conclusions: No clinical study of immunotherapy combined with standard chemotherapy as first-line treatment for advanced unresectable or metastatic thymic epithelial tumors has been described. This article provides strong evidence for the early application or even first-line use of tislelizumab combined with chemotherapy for advanced thymic epithelial tumors. More clinical studies are needed to evaluate the efficacy and safety of tislelizumab in thymic tumors.

Update on thymic epithelial tumors: a narrative review.

Thymoma, thymic carcinoma and thymic neuroendocrine tumors originate from the epithelial cells of the thymus and account for the thymic epithelial tumors (TETs). Although TETs are uncommon, they are the most frequent tumor type in the anterior mediastinum. Multidisciplinary approach is essential for their correct management. The aim of the present review is to summarize the update management for TETs. For this review, we searched in Excerpta Medica database (EMBASE) and MEDLINE until 6 September 2023. The terms used in the search included thymoma, thymic carcinoma, thymic epithelial tumors, management, immunotherapy, multiple tyrosine kinases inhibitors. The therapeutic approach is based on histology and tumor stage and may involve surgery with or without neoadjuvant or adjuvant treatment. In the metastatic setting, platinum-based chemotherapy is the standard of care and patients who do not respond to first-line treatment have limited treatment options mainly because of the poor efficacy shown in subsequent lines of therapy. Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types. Immune check point inhibitors, mammalian target of rapamycin (mTOR) and antiangiogenic multikinase inhibitors have also been studied in this clinical setting.

Combining SBRT with GM-CSF and Peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors.

Combining SBRT with GM-CSF and Peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors.

20 Years of Thymic Tumours in Western Australia

20 Years of Thymic Tumours in Western Australia

RPN1: a pan-cancer biomarker and disulfidptosis regulator.

Elevated expression of SLC7A11, in conjunction with glucose deprivation, has revealed disulfidptosis as an emerging cell death modality. However, the prevalence of disulfidptosis across tumor cell lines, irrespective of SLC7A11 levels, remains uncertain. Additionally, deletion of the ribophorin I (RPN1) gene imparts resistance to disulfidptosis, yet the precise mechanism linking RPN1 to disulfidptosis remains elusive. The aim of this study is to determine the mechanism of RPN1-induced disulfidptosis and to determine the possibility of RPN1 as a pan-cancer marker. We hypothesized the widespread occurrence of disulfidptosis in various tumor cells, and proposed that RPN1-mediated disulfidptosis may be executed through cell skeleton breakdown. Experimental validation was conducted via flow cytometry, immunofluorescence, and western blot techniques. Furthermore, given RPN1's status as an emerging cell death marker, we utilized bioinformatics to analyze its expression in tumor tissues, clinical relevance, mechanisms within the tumor microenvironment, and potential for immunotherapy. Conducting experiments on breast cancer (MDA-MB-231) and lung cancer (A549) cell lines under glucose-starved conditions, we found that RPN1 primarily induces cell skeleton breakdown to facilitate disulfidptosis. RPN1 demonstrated robust messenger RNA (mRNA) expression across 16 solid tumors, validated by data from 12 tumor types in the Gene Expression Omnibus (GEO). Across 12 cancer types, RPN1 exhibited significant diagnostic potential, particularly excelling in accuracy for glioblastoma (GBM). Elevated RPN1 expression in tumor tissues was found to correlate with improved overall survival (OS) in certain cancers [diffuse large B-cell lymphoma (DLBC) and thymoma (THYM)] but poorer prognosis in others [adrenocortical carcinoma (ACC), kidney chromophobe (KICH), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD)]. RPN1 is enriched in immune-related pathways and correlates with immune scores in tumor tissues. In urothelial carcinoma (UCC), RPN1 demonstrates potential in predicting the efficacy of anti-programmed cell death ligand 1 (PD-L1) immune therapy. This study underscores RPN1's role in facilitating disulfidptosis, its broad relevance as a pan-cancer biomarker, and its association with the efficacy of anti-PD-L1 immune therapy.

Robotic surgery for thymic cysts: clinical features, management, and results of a multicentric study.

Thymic cysts are rare, radiological diagnosis is often incidental, and cysts seldom assume clinical relevance for symptoms of compression. Thymoma were occasionally found inside both complex and simple thymic cysts. Given the challenges in accurately clinical diagnosing and since the occasionally discovering of thymoma inside both complex and simple thymic cysts, the management of thymic cysts remains controversial. Advancements in surgical tools such as robotics, applied to thymic conditions, could potentially transform the approach to thymic cysts. We report one the largest multicentric series of thymic cysts surgically treated with robotic approach, focusing on preoperative findings and surgical results. Cases were gathered from three Italian thoracic surgery centers with homogeneous clinical practice, significant experience in thymic neoplasms, and thoracic robotic skilled. Surgical intervention was indicated for patients with radiological diagnosis of thymic cysts under the following circumstances: the presence of symptoms, concurrent myasthenia gravis, cysts growing in follow-up, and the complexity of the cyst with suspicion of neoplasm. Data were collected and matched according to postoperative and pathological features to identify potential prognostic factors. Population include 57 patients, 29/28 male/female ratio with mean age of 59.46 ± 11.67years. The average size of the thymic cysts was 29.14 ± 24.53 ranged between 3 and 150mm. All patients undergone CT scan and mean of values of density was 25.82 ± 11-82 Hounsfield. Surgical procedures were robotic approach in all case including total/extended thymectomy 35 (61.4%) and cyst resection/partial thymectomy 22 (38.6%). There were no mortality or recurrence. Major complications rate was 5.3%. No correlations were observed between preoperative features and complication. Pathological examination revealed microfoci of thymic tumor in four cases. Robot-assisted surgery for thymic cysts showed excellent early clinical outcomes with low rate of postoperative complications also in case of large lesion. Thymic cysts should not be underestimated due to the risk of coexistent thymic neoplasm.

Immunotherapy in thymic epithelial tumors: tissue predictive biomarkers for immune checkpoint inhibitors.

Thymic epithelial tumors (TETs) are rare malignant neoplasms arising in the thymus gland. Nevertheless, TETs, including thymomas (TMs), thymic carcinomas (TCs), and thymic neuroendocrine neoplasms (TNENs), are the most common mediastinal malignancies overall. A multidisciplinary approach is required for the appropriate diagnostic and therapeutic management of TETs. To date, the main therapeutic strategies are largely depended on the stage of the tumor and they include surgery with or without neoadjuvant or adjuvant therapy, represented by platinum-based chemotherapy, radiotherapy or chemoradiotherapy. Immune checkpoint inhibitors (ICIs) are ongoing under evaluation in the advanced or metastatic diseases despite the challenges related to the very low tumor mutation burden (TMB) and the high incidence of immune-related adverse events in TETs. In this regard, predictive impact of tissue biomarkers expression such as programmed cell death ligand-1 (PD-L1), and other emerging biomarkers, as well as their optimal and shared interpretation are currently under evaluation in order to predict response rates to ICIs in TETs.

Identification of cytokines in benign and malignant thymus tumors: based on Mendelian randomization and proteomics.

The aim of this study was to identify potential causal cytokines in thymic malignancies and benign tumors from the FinnGen database using Mendelian randomization (MR). In this study, data from genome-wide association studies (GWAS) of 91 cytokines were used as exposure factors, and those of thymic malignant tumors and thymic benign tumors were the outcome variables. Two methods were used to determine the causal relationship between exposure factors and outcome variables: inverse variance weighting (IVW) and MR-Egger regression. Sensitivity analysis was performed using three methods, namely, the heterogeneity test, the pleiotropy test, and the leave-one-out test. There was a causal relationship between the expression of fibroblast growth factor 5, which is a risk factor for thymic malignant tumors, and thymic malignant tumors. C-C motif chemokine 19 expression, T-cell surface glycoprotein CD5 levels, and interleukin-12 subunit beta levels were causally related to thymic malignant tumors and were protective. Adenosine deaminase levels, interleukin-10 receptor subunit beta expression, tumor necrosis factor (TNF)-related apoptosis-inducing ligand levels, and TNF-related activation-induced cytokine levels showed a causal relationship with thymic benign tumors, which are its risk factors. Caspase 8 levels, C-C motif chemokine 28 levels, interleukin-12 subunit beta levels, latency-associated peptide transforming growth factor beta 1 levels, and programmed cell death 1 ligand 1 expression showed a causal relationship with thymic benign tumors, which are protective factors. Sensitivity analysis showed no heterogeneity. Cytokines showed a causal relationship with benign and malignant thymic tumors. Interleukin-12 subunit beta is a common cytokine that affects malignant and benign thymic tumors.

Atypical thymic carcinoid tumour with ectopic ACTH syndrome: a rare case with a good prognosis

Atypical thymic carcinoid tumour with ectopic ACTH syndrome: a rare case with a good prognosis

Successful management of thymic neuroendocrine tumour with paraneoplastic limbic encephalitis.

A 42-year-old man was referred to psychiatry with acute onset of confusion and agitation. His screening computed tomography scan showed middle mediastinal tumours. Preoperative cerebrospinal fluid analysis was positive for anti-contactin-associated protein-like 2 antibody; possible paraneoplastic limbic encephalitis was diagnosed. Tumour resection was performed. Pathological examination showed thymic neuroendocrine tumour, stage IV. Postoperatively, the patient was treated with everolimus for adjuvant therapy, with complete improvement of encephalitis symptoms. The patient remained well without tumour recurrence or exacerbation of psychiatric disorders for 14 months after the operation.

Extended abstract: radiomics and artificial intelligence in thymic tumors

Extended abstract: radiomics and artificial intelligence in thymic tumors

Thymic Imaging Pitfalls and Strategies for Optimized Diagnosis.

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.

Safety and Efficacy of Transsternal Core Biopsy of Anterior Mediastinal Masses

BackgroundThe study evaluated the safety and adequacy of percutaneous transsternal anterior mediastinal core biopsy. MethodsAll percutaneous computed tomography–guided transsternal mediastinal 18-gauge core biopsies performed at 2 academic centers were retrospectively reviewed. Procedural, clinical, and pathology data were recorded. ResultsSixteen patients underwent biopsies. Nine had preexisting cancer diagnoses. Biopsy was performed with general anesthesia (3), monitored anesthesia care (7), and moderate sedation (6). All patients were discharged the same day, except 1 patient, in whom a pneumothorax developed, necessitating chest tube placement. Of 16 biopsies, 15 (94%) yielded pathologic diagnoses, including thymoma (4), benign lesion (3), and 8 malignant neoplasms (3 lung cancer, 3 lymphoma, 1 thymic carcinoid tumor, 1 sarcoma). In most (14/16), ≥3 core specimens were obtained. In the nondiagnostic biopsy, only 1 core was obtained. Tissue was adequate in 4 of 6 cases for ancillary testing. Eight patients received diagnoses from core biopsy indicating observation or medical therapy, obviating the need for an operation. ConclusionsOutpatient transsternal anterior mediastinal 18-gauge core biopsy is feasible, safe, and effective and may prevent unnecessary operations. Obtaining ≥3 cores may optimize diagnostic yield.

Molecular pathology/genetics of thymic tumors: extended abstract

Molecular pathology/genetics of thymic tumors: extended abstract

A Re-Examination of Neoadjuvant Therapy for Thymic Tumors: A Long and Winding Road.

For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of preoperative therapy. But studies on neoadjuvant chemotherapy have included mainly patients with thymoma; its efficacy in patients with thymic carcinoma is less known. Neoadjuvant chemoradiation has also been explored in a few studies. Novel therapies such as immunotherapy and targeted therapy have shown efficacy in patients with recurrent/metastatic TETs as a second-line option; their role as preoperative therapy is still under investigation. In this review, we discuss the existing evidence on preoperative therapy and the insight it provides for current clinical practice and future studies.