RARE DISEASE
Thymoma
Thymoma
Thymoma
Synonyms: Primary thymic epithelial neoplasm, Primary thymic epithelial tumor
Synonyms: Primary thymic epithelial neoplasm, Primary thymic epithelial tumor
Synonyms: Primary thymic epithelial neoplasm, Primary thymic epithelial tumor
Drug discovery
3
drugs
With orphan designations
Overview
Thymoma is a rare thymic epithelial neoplasm arising in the anterior mediastinum, primarily affecting adults aged 40-70. These tumors demonstrate indolent growth but may metastasize to pleural/pericardial surfaces. Approximately 40% associate with autoimmune paraneoplastic syndromes like myasthenia gravis [4][15]. Staging by Masaoka-Koga system guides treatment, which typically combines surgery with adjuvant therapies for advanced cases [1][5].
Therapies
Surgical resection: Gold standard for localized disease (Masaoka I-II), increasingly via minimally invasive techniques (VATS/RATS) [1][16]
Multimodality therapy: Neoadjuvant platinum-based chemotherapy (e.g., cisplatin + anthracyclines) for stage III/IV, followed by surgery/radiotherapy [3][8][13]
Advanced/metastatic disease: Targeted therapies (sunitinib, lenvatinib) and immunotherapy (pembrolizumab) for refractory cases [6][13][15]
Categories: rare neoplastic diseases
Research Papers
2,201 drug discovery papers about Thymoma, with 1 first-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
2,201 drug discovery papers about Thymoma, with 1 first-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2025-09-21 | PERM associated with thymic carcinoma with triple-autoantibody positivity: case report and literature review.
Progressive encephalomyelitis with rigidity and myoclonus (PERM) represents a severe Stiff-person syndrome (SPS) variant with brainstem and autonomic involvement. Although PERM is occasionally paraneoplastic-typically associated with antibodies such as anti-GAD, anti-GlyR, and anti-amphiphysin-its association with thymic carcinoma has not been previously described. To report a case of PERM associated with thymic carcinoma and triple autoantibody positivity in cerebrospinal fluid (CSF), and to review the literature on paraneoplastic and multiple-antibody PERM. A literature review of paraneoplastic and multiple-antibody PERM cases was conducted in English. The case report follows CARE guidelines. A 47-year-old Mexican-mestizo female patient was diagnosed with PERM secondary to stage IIIB thymic carcinoma. Brain MRI revealed hyperintensities in the mesial temporal and orbitofrontal regions. CSF analysis showed anti-GAD65, anti-amphiphysin, and anti-titin antibodies. Intravenous immunoglobulin therapy resulted in marked clinical improvement. The literature review demonstrated wide clinical and immunological heterogeneity. Most patients were female, typically presenting in later adulthood. Anti-GAD was the most frequent antibody, often coexisting with others in thymoma-associated cases. Presentations were consistently severe, often involving neuropsychiatric, autonomic, and brainstem symptoms, despite frequently unremarkable MRI findings. Coexisting antibodies in paraneoplastic cases were linked to more aggressive disease, while anti-GlyR positivity was associated with milder presentations and better treatment response. Early immunotherapy was generally beneficial. This case highlights the need for timely oncologic and immunologic evaluation in atypical SPS presentations and underscores the therapeutic importance of early diagnosis and treatment.
2025-06-23 | Patient With Advanced Aggressive B2 Thymoma Achieved Positive Outcomes Post CAP-Endostar Combination Therapy.
This case report features a patient with an invasive thymoma. The patient presented with an anterior mediastinal mass that invaded the left brachiocephalic trunk vein, resulting in the formation of a carcinoma thrombus in the right atrium, superior vena cava, left brachiocephalic trunk vein, and left internal jugular vein (Masaoka stage IV). No indication for surgery was assessed by surgical consultation. After six cycles of chemotherapy and chest radiotherapy, the tumor size decreased from 72.43 to 24 mm, showing a significant improvement in patient efficacy. After a follow-up of 50 months, the patient remained well, without local recurrence or distal metastasis, and maintained a partial response (PR).
2025-06-12 | An update on the therapeutic options for metastatic thymomas and thymic carcinomas.
Thymic epithelial tumors are rare cancers originating from the thymus, with an annual incidence of 0.13 per 100,000 persons. Therefore, the standard of care was approved primarily based on the results of single-arm phase II trials. If the disease is resectable and localized, a multidisciplinary treatment combining surgical resection, radiotherapy, and pharmacotherapy should be considered. Pharmacotherapy is the mainstay of treatment for metastatic and recurrent diseases. This review delineates the distinct difference in treatment strategies of chemotherapy in patients with thymomas and thymic carcinomas. Thymomas typically respond to a cisplatin and anthracyclines, often supplemented with steroids, whereas thymic carcinomas, which do not typically involve anthracyclines as key drugs, are treated with platinum-based doublet chemotherapy. Lenvatinib has emerged as a pivotal key drug for refractory thymic carcinoma. In addition, single-agent cytotoxic chemotherapy, molecular targeted therapies, and immune checkpoint inhibitors is considered as key drugs for thymic carcinomas. Current research is focused on developing novel therapeutics such as antibody-drug conjugates (ADCs), angiogenesis inhibitors, multi-kinase inhibitors, and further immune checkpoint inhibitors, expanding the prospects for pharmacotherapy in thymic malignancies.
2025-04-26 | Correction of changes in lung tissue during complex treatment malignant thymoma
Thymoma is a rare malignancy, clinical signs are non-specific, and the disease may be asymptomatic for a long time. The aim of this report is to highlight the complexity of treatment of a patient with IV stage of the disease. Research methods such as observation and analysis of data obtained as a result of correction of complications of antitumour treatment of the patient were used in the work. According to the results obtained, the multimodal approach to the complex treatment of patients with locally advanced process makes it advisable to observe for post-radiation and postoperative complications and their correction.
2025-03-24 | Pure White Cell Aplasia, an Exceedingly Rare Complication of a Thymoma, and Immune Reconstitution Following Bone Marrow Recovery.
Thymoma-associated pure white cell aplasia (PWCA), characterized by agranulocytosis with absent myeloid precursors in the bone marrow in the setting of preserved erythropoiesis and megakaryopoiesis, is exceedingly rare, with only a few cases reported in the literature. We present a case of type-B2-thymoma-associated PWCA and immune reconstitution following marrow recovery. A 75-year-old woman was incidentally found to have a concomitant mediastinal mass and peripheral leukopenia with absent granulocytes and monocytes. Bone marrow assessment was notable for a hypocellular marrow (<10%) with absent granulopoiesis and monopoiesis. Chest CT demonstrated a large lobulated anterior mediastinal mass, for which the patient underwent a video-assisted thoracoscopic thymectomy. Pathological evaluation of the mediastinal mass specimen revealed a type B2 thymoma. A tentative diagnosis of thymoma-associated PWCA was made, and the patient was started on cyclosporine/granulocyte-colony stimulating factor (G-CSF)/filgrastim therapy. Despite promising marrow recovery, she developed several comorbidities and had a leukemoid reaction, provoking concern for immune reconstitution following prolonged neutropenia and subsequent treatment. She passed away on post-operative day 15, and the results of a post-mortem bone marrow examination were consistent with granulocytic hyperplasia. This case of thymoma-associated PWCA heightens awareness regarding this entity, providing a note of caution regarding the possibility of immune reconstitution following treatment and marrow recovery.
small molecules
2026-09-25 | Fulminant immune checkpoint inhibitor-associated myositis presenting with concurrent myocardial injury and secondary cardiogenic shock in a patient with thymoma: a case report and literature review.
Immune checkpoint inhibitor (ICI)-associated toxicities are uncommon but may rapidly progress to cardiogenic shock and death. Patients with thymoma are considered particularly vulnerable to severe immune-related adverse events because thymic malignancy is closely associated with impaired central immune tolerance and autoimmune dysregulation. We report a 34-year-old man with stage IV type B2 thymoma who developed initial myalgia and fatigue approximately 15 days after the most recent pembrolizumab-containing treatment cycle and progressed to fulminant ICI-associated myositis with respiratory failure and secondary cardiogenic shock by day 19. He presented with severe immune-mediated myositis, concurrent myocardial injury, left ventricular systolic dysfunction, cardiogenic shock, metabolic acidosis, acute kidney injury, acute liver injury, coagulopathy, and respiratory failure. Coronary angiography excluded obstructive coronary disease, and microbiological and virological investigations did not identify an infectious cause. Endomyocardial biopsy and cardiac magnetic resonance imaging were not feasible because of profound hemodynamic instability, VA-ECMO support, and coagulopathy. The patient was treated with early venoarterial extracorporeal membrane oxygenation (VA-ECMO), high-dose methylprednisolone, intravenous immunoglobulin, continuous renal replacement therapy, mechanical ventilation, and comprehensive organ support. Cardiac function improved from a left ventricular ejection fraction of 25% to 51%, VA-ECMO was discontinued on hospital day 7, and the patient survived to discharge. This case and a focused literature review suggest that thymoma-associated ICI myositis with secondary cardiac dysfunction may represent a high-risk phenotype characterized by early onset, overlap neuromuscular toxicity, severe hemodynamic compromise, and potential reversibility when early immunosuppression and advanced circulatory support are implemented.
2026-09-20 | Invasive thymoma with rapid response to cisplatin, doxorubicin and cyclophosphamide (PAC) chemotherapy, after an early postoperative recurrence-a case report.
Thymomas generally exhibit indolent growth and local progression, with extrathoracic metastases being rare. Recurrence typically occurs months or years after surgical resection. We herein present a rare case of thymoma exhibiting rapid postoperative recurrence and abdominal lymph node metastasis, which showed a dramatic response to chemotherapy. A 66-year-old female was referred to our hospital for breast cancer treatment. A preoperative computed tomography (CT) scan coincidentally revealed a 7.5 cm anterior mediastinal tumor, suspected to be invading the pericardium and left lung. Extended thymothymectomy with partial resection of the left lung and pericardium was performed. Intraoperatively, no pleural dissemination was observed, and pleural effusion cytology was negative for malignant cells. The pathology was Type AB thymoma, Masaoka stage III [tumor, node, metastasis (TNM) 8th edition: pT3N0M0, Stage IIIA; TNM 9th edition: pT2N0M0, Stage II], with microscopically positive (R1) margins; thus, postoperative radiotherapy was planned. On postoperative day (POD) 18, she presented with dyspnea and massive left pleural effusion; after repeated thoracocentesis, the effusion recurred, and the patient was readmitted for continuous drainage. On POD 43, a CT scan showed a massive lesion along the left thoracic wall adjacent to the pericardium, with multiple small nodes in the left lung and two enlarged left gastric lymph nodes. A CT-guided needle biopsy of the thoracic wall performed on POD 47 confirmed recurrent thymoma. The patient received chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (PAC), with biochemical evidence of rapid tumor lysis that did not meet formal tumor lysis syndrome criteria. Chest X-ray on day 3 of chemotherapy showed near-complete resolution of the thoracic lesions, and a complete response, including normalization of the abdominal lymph nodes, was achieved after four courses of PAC. Serial follow-up imaging has shown no evidence of recurrence for at least 18 months. This case illustrates the diagnostic complexity of thymoma, including atypical radiological and pathological features together with an unusually aggressive early recurrence. Incomplete resection can lead to early recurrence and progression, and clinicians must remain vigilant for such atypical courses. The tumor nonetheless proved highly sensitive to chemotherapy, underscoring the importance of prompt systemic treatment intervention when recurrence occurs.
2026-09-20 | Narrative review: locally advanced thymoma-do we really need induction therapy before extended resection?
Locally advanced thymoma remains a challenging condition in which complete tumour clearance may require extended surgical resection. Induction therapy, including chemotherapy or chemoradiotherapy, is used in selected patients to improve resectability; however, the evidence supporting its routine use remains limited. This narrative review evaluates the role of induction therapy before extended resection, with particular attention to patient selection, resectability assessment, and multidisciplinary decision-making. A structured narrative review was conducted using PubMed/MEDLINE, supplemented by manual screening of reference lists from relevant articles, reviews, registry analyses, and guideline documents. The original search covered the period from January 1990 to April 2026 and was updated on 21 June 2026 during revision. Search terms included combinations of "thymoma", "thymic epithelial tumours", "locally advanced", "induction therapy", "neoadjuvant treatment", "preoperative chemotherapy", "chemoradiotherapy", "resectability", "borderline resectable", and "extended resection". English-language clinical studies, systematic and narrative reviews, registry analyses, and international guidelines were considered. The available evidence is largely derived from retrospective, heterogeneous studies, often including mixed populations of thymoma and thymic carcinoma. Platinum-based regimens can achieve radiologic response rates of approximately 50-70%, but no prospective or randomised data demonstrate a clear survival advantage over upfront surgery in clearly resectable thymoma. Induction therapy may provide practical advantages in selected anatomically complex or borderline-resectable cases, including tumour bulk reduction, improved operative planning, and potential facilitation of margin-negative resection. However, radiologic response does not necessarily indicate true pathologic downstaging or reduced need for en bloc resection. Current evidence therefore supports a selective, rather than routine, use of induction therapy following multidisciplinary assessment. Extended surgical resection remains the standard of care when complete resection appears achievable upfront. Current evidence is insufficient to support routine induction therapy in clearly resectable locally advanced thymoma, although induction treatment remains appropriate in selected borderline-resectable cases in which preoperative therapy may improve the likelihood or quality of complete resection. Further prospective and collaborative studies are needed to refine patient selection and clarify its role.
2026-09-20 | Very late recurrence of thymoma after 14 years: an International Thymic Malignancy Interest Group Tumor Board case report from a Turkish multidisciplinary team.
Thymomas are generally slow-growing tumors with a favorable prognosis; however, late recurrences have been well documented in the literature and may occur many years after complete (R0) resection. In this report, the multimodal management of a patient who experienced recurrence 14 years after surgery is presented as discussed during the multidisciplinary International Thymic Malignancy Interest Group (ITMIG) Tumor Board meeting on 17 October 2025. An 18-year-old female patient underwent median sternotomy in 2006 for resection of a 15.5-cm type B1 thymoma. Histopathological examination revealed microscopic transcapsular invasion with negative surgical margins, and adjuvant therapy was not recommended at that time. In 2020, progressive myasthenic symptoms led to re-evaluation, and imaging demonstrated multifocal right pleural recurrence with suspected involvement of the inferior vena cava and hepatic interface. Fine-needle aspiration biopsy confirmed recurrent World Health Organization (WHO) type B1 thymoma. Because complete resection was considered unlikely, the patient received cisplatin/etoposide chemotherapy followed by definitive chemoradiotherapy, achieving major radiologic response and disease stability. In 2024, after progression of a paravertebral recurrent lesion, salvage surgery was performed via right thoracotomy, including wedge resection, pleurectomy, mediastinal lymph node dissection, and intraoperative hyperthermic intrathoracic chemotherapy. The patient has since remained disease-free on continued surveillance. In thymic epithelial tumors with increased risk of recurrence, multimodal treatment strategies may improve long-term outcomes. This case highlights that very late recurrence may occur even after R0 resection and supports lifelong surveillance. Long-term follow-up should include periodic contrast-enhanced thoracic computed tomography, with magnetic resonance imaging considered in younger patients to reduce cumulative radiation exposure.
2026-09-13 | Robotic Resection With Hyperthermic Intrathoracic Perfusion Chemotherapy for Thymoma Recurrence.
Thymoma recurrence with pleural dissemination remains a therapeutic challenge, often requiring multimodal treatment strategies. Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (HITHOC) has emerged as a promising approach for selected patients; however, reports using minimally invasive robotic platforms are limited. We present the case of a 41-year-old woman with pleural and lymph node recurrence of type AB thymoma 3 years after robotic extended thymectomy. The patient underwent robotic-assisted cytoreductive surgery, including complete parietal pleurectomy and resection of pleural, pericardial, and subaortic lymph node lesions, followed by HITHOC with cisplatin and doxorubicin. The procedure was performed safely, with no major perioperative complications. The patient was discharged after 7 days and remained disease-free at 2-year follow-up. This case highlights the feasibility, safety, and potential oncological benefits of combining robotic cytoreductive surgery with HITHOC in the management of recurrent thymoma with pleural involvement. This minimally invasive multimodal strategy may represent a valuable option for carefully selected patients, although further studies with larger cohorts and longer follow-up are warranted.
cell therapies
2026-04-21 | Left brachiocephalic vein replacement and superior vena cava reconstruction with aortic homograft for thymic carcinoma.
Advanced intrathoracic tumours pose a significant challenge for thoracic surgeons because of the possible involvement of adjacent vital organs and major mediastinal vessels. The most effective therapeutic option for resectable thymic carcinomas is currently represented by complete surgical asportation en bloc with adjacent infiltrated structures to achieve more effective oncological outcomes. Vascular reconstruction, when required, is traditionally performed using prosthetic conduits; however, vascular homografts represent a potential alternative with several surgical and clinical advantages. We report a case of a large thymic carcinoma with mediastinal vessel invasion successfully treated by surgical resection and vascular reconstruction using an aortic homograft.
2026-03-14 | When Central Tolerance Fails: Thymic Malignancies at the Intersection of Cancer Immunity and Autoimmunity.
Thymic malignancies are rare cancers arising from thymic epithelial cells and are characterized by a highly diverse clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent associations with autoimmune syndromes. Although the clinical, immunological, and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumor staging and histological grading in shaping autoimmunity burden and infection risk. In this narrative review, we synthesize contemporary clinical, immunological, and morphologic evidence linking thymic architecture and selection defects to the spectrum of paraneoplastic autoimmunity (MG, pure red cell aplasia, Good's syndrome) and to infectious vulnerability. We further appraise emerging therapeutic strategies, including immune checkpoint inhibition and adoptive cellular approaches, through a patient-stratified lens, emphasizing efficacy signals, immune-related adverse events, and practical considerations for selection and monitoring. We conclude by highlighting priorities for future investigation, including refining autoantibody signatures; mapping thymic microenvironments that drive tolerance failure, and prospectively evaluating stratified immunotherapeutic regimens that balance benefit with immune-mediated risk.
2025-02-20 | Advanced thymic epithelial tumour resection: vascular resection and reconstruction strategy.
Thymic epithelial tumors (TETs) represent the predominant primary malignancy of the anterior mediastinum, often necessitating complex surgical interventions due to their invasive nature. The prognosis of advanced TET relies significantly on achieving complete resection with microscopically clear margins (R0). This frequently entails resection and reconstruction of major vascular structures like the superior vena cava (SVC) and brachiocephalic veins, and in some cases, extra pleural pneumonectomy (EPP). The aim of the study is to interrogate our series of advanced TET resections. We analysed our experience with vascular resection and reconstruction in 14 patients with advanced stage III/IV TET undergoing extensive resection post-neoadjuvant chemotherapy. A comprehensive preoperative evaluation was performed, including computed tomography (CT), positron emission tomography (PET), biopsy, and exercise testing. We describe our surgical approach and the details of our series. From 2015 to 2023, 31 patients underwent surgery for advanced TET at our centre, with major vessel reconstruction performed in 14 cases. This included resection of SVC and innominate veins with subsequent reconstruction using polytetrafluoroethylene (PTFE) grafts. The median operative time was 350 minutes, with a median blood loss of 1,300 mL. Cardiopulmonary bypass (CPB) was required in 2 cases. The rate of R0 resection was 78.6%, with a recurrence rate of 14.3% at a median follow-up of 1,700 days. Postoperative complications occurred in 42.9% of patients, with an in-hospital mortality rate of 7.1%. Multi-disciplinary management, meticulous preoperative planning, and advanced surgical techniques are essential for the successful treatment of advanced TET. Complex vascular resections should be reserved for high-volume centres to optimize outcomes.
2025-01-08 | Multimodal management and complete resection of invasive Type B3 thymoma with vascular reconstruction: a case report.
Thymomas and thymic carcinomas are rare anterior mediastinal tumours, accounting for 0.2-1.5% of all cancers. Surgical resection is key to treatment, though invasion of surrounding structures like great vessels can complicate this. This case report details the management of a type B3 thymoma (T4 N0 M0) in a 41-year-old male. A 41-year-old male presented with myasthenic symptoms and was diagnosed with a large thymic mass involving the brachiocephalic vein and superior vena cava. After 4 cycles of neoadjuvant chemotherapy, partial resection was performed, followed by radiotherapy. Residual disease led to a second surgery, during which tumour resection and vascular reconstruction using cardiopulmonary bypass were successfully completed. Postoperative recovery was uneventful. Complete resection, including re-resection, when necessary, is crucial for improved outcomes in thymoma patients. Even with great vessel invasion, aggressive surgery, coupled with chemotherapy and vascular reconstruction, can achieve good survival outcomes. Multimodal management, including chemotherapy, complete resection, and vascular reconstruction, offers the best prognosis for invasive thymomas, even with great vessel involvement.
2024-08-04 | Cell Culture Models for Translational Research on Thymomas and Thymic Carcinomas: Current Status and Future Perspectives
Cell culture model systems are fundamental tools for studying cancer biology and identifying therapeutic vulnerabilities in a controlled environment. TET cells are notoriously difficult to culture, with only a few permanent cell lines available. The optimal conditions and requirements for the ex vivo establishment and permanent expansion of TET cells have not been systematically studied, and it is currently unknown whether different TET subtypes require different culture conditions or specific supplements. The few permanent cell lines available represent only type AB thymomas and thymic carcinomas, while attempts to propagate tumor cells derived from type B thymomas so far have been frustrated. It is conceivable that epithelial cells in type B thymomas are critically dependent on their interaction with immature T cells or their three-dimensional scaffold. Extensive studies leading to validated cell culture protocols would be highly desirable and a major advance in the field. Alternative methods such as tumor cell organoid models, patient-derived xenografts, or tissue slices have been sporadically used in TETs, but their specific contributions and advantages remain to be shown.
antibodies
2026-09-24 | Navigating coexisting autoimmunity and immunodeficiency in thymoma: a case report of TAMA, Good's syndrome, and myasthenic crisis.
The coexistence of thymoma-associated multiorgan autoimmunity (TAMA) and Good's syndrome creates a challenging clinical scenario in which autoimmunity and profound immunodeficiency occur simultaneously. Here, we report a 37-year-old female with invasive WHO Type B3 thymoma and myasthenia gravis (MG) who developed progressive erythroderma-like skin lesions with graft-versus-host disease-like interface dermatitis. Immunological evaluation revealed marked hypogammaglobulinemia, absent circulating B cells, reduced CD4+ T cells, and an inverted CD4+/CD8+ ratio. During a subsequent myasthenic crisis, severe immune dysfunction and active pulmonary infection were already present. Because conventional rapid immunomodulatory options were limited, efgartigimod and eculizumab were administered sequentially. The pulmonary infection continued to progress, and the patient ultimately died. This case highlights the importance of immune and infection risk assessment before potent immunomodulatory therapy.
2026-09-23 | Ivonescimab plus chemotherapy as first-line treatment for advanced thymic carcinoma: preliminary results of a phase II trial with biomarker analyses.
Thymic carcinoma is a rare, aggressive malignancy with limited treatment options. First-line platinum-based chemotherapy yields response rates below 40%, and immune checkpoint inhibitors have shown inconsistent efficacy. Ivonescimab, a programmed cell death protein 1/vascular endothelial growth factor (PD-1/VEGF) bispecific antibody, may enhance antitumor activity through dual blockade.This single-center, phase II trial enrolled patients with stage IVb, treatment-naïve thymic carcinoma. Patients received ivonescimab (20 mg/kg) plus paclitaxel (175 mg/m²) and carboplatin (area under the curve 5) every 3 weeks for four to six cycles, followed by ivonescimab maintenance. The primary endpoint was objective response rate (ORR) . Secondary endpoints included disease control rate (DCR) and safety. Biomarker analyses were exploratory.Between January 2025 and April 2026, seven patients were enrolled (median age 61 years; 71% male; 71% squamous). Five had evaluable tissue next-generation sequencing and six had transcriptomic data. After median follow-up of 6.4 months, the preliminary ORR was 85.7% (6/7; 95% CI 42.1% to 99.6%) and DCR 100%. The 6-month progression-free survival (PFS) and overall survival (OS) rates were both 100% (two and four patients at risk for PFS and OS, respectively). The only PFS event occurred at 15.7 months in a patient who discontinued treatment due to adverse events (AEs). Grade ≥3 treatment-related AEs occurred in 57.1% (mainly neutropenia, 42.9%); grade ≥3 immune-related AEs in 14.3%. No treatment-related deaths occurred. All tumors were microsatellite-stable with low mutational burden. Deep responders (≥50% reduction) showed a lower exploratory myeloid-derived suppressor cell-related gene-expression score (nominal p=0.10, exact Mann-Whitney U test). Baseline blood CD4+/CD8+ ratio was lower in deep responders and remained stable during treatment, vs an increase in others (nominal p=0.057). Tumorous CXCL1 expression showed an exploratory positive correlation with the CD4+/CD8+ ratio (R=0.84, nominal p=0.035, n=6).First-line ivonescimab plus paclitaxel-carboplatin showed promising preliminary antitumor activity and manageable safety in advanced thymic carcinoma. The peripheral blood CD4+/CD8+ ratio showed an exploratory association with depth of response and warrants prospective evaluation in the complete cohort and independent validation.Trial registration numberChiCTR2400094398.
2026-09-11 | Immune checkpoint inhibitors in thymic epithelial tumors: current evidence, immune-related toxicity, and perioperative considerations-a narrative review.
Thymic epithelial tumors (TETs) are rare mediastinal malignancies with unique immunobiological features related to thymic immune tolerance. Although immune checkpoint inhibitors (ICIs) have shown clinical activity, especially in thymic carcinoma, their use is limited by frequent and sometimes severe immune-related adverse events (irAEs), particularly in thymoma. This review summarizes current evidence on the efficacy, toxicity, biomarkers, and perioperative implications of ICIs in TETs. A narrative review was conducted using PubMed, Web of Science, and Embase for English-language studies on ICIs in TETs published from database inception to September 2025. Reference lists of relevant articles and guideline papers were also manually screened. Prospective trials, retrospective cohorts, guideline papers, and key mechanistic studies were prioritized, with emphasis on histology-specific efficacy, irAEs, biomarkers, and perioperative application. Current evidence suggests that ICIs have more consistent antitumor activity in thymic carcinoma than in thymoma. In contrast, thymoma carries a substantially higher risk of severe early irAEs, particularly myocarditis, myositis, and myasthenia gravis overlap syndromes. Biomarkers such as programmed death-ligand 1 (PD-L1) expression and immune-related signatures remain promising but are not yet sufficiently validated for routine patient selection. Perioperative immunotherapy is an emerging strategy, but current evidence remains limited and safety concerns are significant. ICIs represent a promising treatment option for selected patients with advanced TETs, particularly thymic carcinoma, but their clinical use remains restricted by toxicity and limited evidence. Future progress will depend on better risk stratification, biomarker-guided selection, and safer multidisciplinary integration.
2026-08-04 | Case Report: Efgartigimod: a beacon of hope for overlapping stiff-person syndrome and myasthenia gravis following thymoma.
The coexistence of stiff person syndrome (SPS) and myasthenia gravis (MG) is exceptionally rare, with fewer than 20 cases reported to date. Thymoma has been identified in a substantial proportion of these patients, suggesting a potential shared autoimmune mechanism. We report a 43-year-old woman who initially presented with progressive limb stiffness, painful muscle spasms, and gait impairment. She was diagnosed with SPS based on positive anti-glutamic acid decarboxylase (GAD) antibodies and characteristic electromyographic findings. Her symptoms improved after immunotherapy but relapsed following corticosteroid withdrawal. Four years later, she developed fluctuating limb weakness and ptosis and was subsequently diagnosed with anti-acetylcholine receptor antibody-positive MG associated with type B2 thymoma. Following thymectomy and postoperative radiotherapy, COVID-19 infection precipitated a myasthenic crisis requiring intensive care support. Conventional treatments, including plasma exchange, intravenous immunoglobulin, corticosteroids, and rituximab, failed to achieve satisfactory clinical improvement. In contrast, treatment with efgartigimod resulted in marked recovery of respiratory and motor function. During follow-up through December 2025, no recurrence of SPS symptoms or MG exacerbation was observed. This case highlights the complex association among SPS, MG, and thymoma and supports the possibility that thymoma may contribute to the development of multiple autoimmune neurological disorders. Furthermore, efgartigimod may represent a promising therapeutic option for refractory thymoma-associated MG in patients with overlapping SPS and MG. Long-term surveillance for thymoma and additional autoimmune manifestations should be considered in patients with SPS.
2026-07-28 | Palliative Systemic Therapy in Advanced Thymic Epithelial Tumors in 2026-A Narrative Review.
Palliative systemic therapy for advanced thymic epithelial tumors (TET) is challenging due to scarce evidence and biological heterogeneity. Scientific discussion, as in this review, is limited to cross-trial comparisons of small, non-randomized studies. Platinum-based combination chemotherapy is the standard first-line treatment. Here, we challenge the addition of anthracyclines to platinum in thymoma. We critically appraise new combinations with antiangiogenic drugs and immune checkpoint inhibitors (ICI) in thymic carcinoma and their implications for therapy sequences. We review the data on classic genomics-based targeted therapy that does not benefit most patients and explore established and upcoming biomarkers including KIT and HER2. Finally, we discuss investigational therapies like anti-TROP2 antibody-drug conjugates and proteasome inhibitors, as well as topics and design of future research.
other
2025-12-07 | Unveiling CCR9 and CCL13 as immune biomarkers and therapeutic targets in thymoma.
This study employed bioinformatics to identify immune-related diagnostic and therapeutic target genes in thymoma, offering a theoretical foundation for clinical diagnosis and treatment of the disease. In this study, machine learning techniques were employed to identify and validate potential biomarkers, leading to the construction of a diagnostic nomogram. Immune infiltration analysis was subsequently conducted to explore the relationships between these biomarkers and immune cell populations. Finally, the findings were validated through RT-qPCR and Western blotting experiments, ensuring the robustness of the results. Three critical biomarkers were selected for thymoma, with CCR9 and CCL13 confirmed as the final biomarkers through ROC analysis, both demonstrating AUC values exceeding 0.7. Immune infiltration analysis revealed significant differences in 14 types of immune cells between the thymoma and control groups, highlighting a strong association between macrophages and the biomarkers. A nomogram for thymoma was constructed using these 2 biomarkers, exhibiting robust performance. Ultimately, validation experiments using RT-qPCR and Western blotting confirmed the consistency of CCR9 and CCLI3 expression with the bioinformatics results. CCR9 and CCL13 were identified in this study as immune-related biomarkers associated with thymoma, which might provide a theoretical foundation for the development of targeted gene therapies.
2025-02-14 | Targeting vaccines to dendritic cells by mimicking the processing and presentation of antigens in xenotransplant rejection.
Targeting the delivery of vaccines to dendritic cells (DCs) is challenging. Here we show that, by mimicking the fast and strong antigen processing and presentation that occurs during the rejection of xenotransplanted tissue, xenogeneic cell membrane-derived vesicles exposing tissue-specific antibodies can be leveraged to deliver peptide antigens and mRNA-encoded antigens to DCs. In mice with murine melanoma and murine thymoma, xenogeneic vesicles encapsulating a tumour-derived antigenic peptide or coated on lipid nanoparticles encapsulating an mRNA coding for a tumour antigen elicited potent tumour-specific T-cell responses that inhibited tumour growth. Mice immunized with xenogeneic vesicle-coated lipid nanoparticles encapsulating an mRNA encoding for the spike protein of severe acute respiratory syndrome coronavirus 2 elicited titres of anti-spike receptor-binding domain immunoglobulin G and of neutralizing antibodies that were approximately 32-fold and 6-fold, respectively, those elicited by a commercialized mRNA-lipid nanoparticle vaccine. The advantages of mimicking the biological recognition between immunoglobulin G on xenogeneic vesicles and fragment crystallizable receptors on DCs may justify the assessment of the safety risks of using animal-derived biological products in humans.
2024-10-18 | Enhancing preventive and therapeutic cancer vaccine efficacy through biotherapeutic ligand-associated extracellular vesicles.
Extracellular vesicles (EVs), secreted by almost all living cells, have gained significant attention for their role in intercellular communication and their potential as versatile carriers for biotherapeutics. However, the clinical translation of EV-based therapies faces significant challenges, primarily due to the lack of efficient methods for loading biotherapeutic agents into EVs. This study introduces a simple, reproducible strategy for the simultaneous incorporation of various biotherapeutics within EVs. The process is gentle and preserves the essential physicochemical and biological characteristics of EVs, thereby protecting labile ligands from premature degradation and elimination. The binding and uptake efficiency of EVs by target cells reached approximately 97 % within 24 h of incubation. Administration of EVs loaded with oligodeoxynucleotides (ODN) resulted in a 4-fold increase in IFNγ+ CD4+ T cells and a 5-fold increase in IFNγ+ CD8+ T cells in the spleens and lymph nodes. Additionally, the co-administration of EVs with ODN and ovalbumin (OVA) induced elevated Th1-biased antibody responses and antigen-specific cytotoxic T-cell responses, providing long-lasting complete protection in 60 % of mice against T-cell thymoma challenge. Furthermore, EVs associated with three different ligands (OVA, CpG-ODN, and α-GalCer) effectively regressed established murine melanoma and significantly improved survival rates in mice. This study presents a powerful and promising approach to overcoming the limitations of EV-based cancer vaccines, advancing the development of effective cancer immunotherapies. SUMMARY: Immunization with EVs that are co-associated with antigen and biotherapeutic cargo through a lyophilization-based technique elicits potent anti-cancer immunity.
2024-06-03 | Single-Cell Sequencing Illuminates Thymic Development: An Updated Framework for Understanding Thymic Epithelial Tumors.
Thymic epithelial tumors (TETs) are rare tumors for which treatment options are limited. The ongoing need for improved systemic therapies reflects a limited understanding of tumor biology as well as the normal thymus. The essential role of the thymus in adaptive immunity is largely effected by its epithelial compartment, which directs thymocyte (T-cell) differentiation and immunologic self-tolerance. With aging, the thymus undergoes involution whereby epithelial tissue is replaced by adipose and other connective tissue, decreasing immature T-cell production. Against this natural drive toward involution, a fraction of thymuses will instead undergo oncologic transformation, leading to the formation of TETs, including thymoma and thymic carcinoma. The rarity of these tumors restricts investigation of the mechanisms of tumorigenesis and development of rational treatment options. To this end, the development of technologies which allow deep molecular profiling of individual tumor cells permits a new window through which to view normal thymic development and contrast the malignant changes that result in oncogenic transformation. In this review, we describe the findings of recent illuminating studies on the diversity of cell types within the epithelial compartment through thymic differentiation and aging. We contextualize these findings around important unanswered questions regarding the spectrum of known somatic tumor alterations, cell of origin, and tumor heterogeneity. The perspectives informed by single-cell molecular profiling offer new approaches to clinical and basic investigation of thymic epithelial tumors, with the potential to accelerate development of improved therapeutic strategies to address ongoing unmet needs in these rare tumors.
2023-12-09 | The Role of Gene Fusions in Thymic Epithelial Tumors.
Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional studies have identified a number of interesting molecular aberrations in TET, including gene fusions in a subset of these tumors. These gene fusions can aid in the diagnosis, shed light on the pathogenesis of a subset of tumors, and potentially may provide patients with the opportunity to undergo targeted therapy or participation in clinical trials. Gene fusions that have been identified in TET include MAML2 rearrangements in 50% to 56% of mucoepidermoid carcinomas (MAML2::CRTC1), 77% to 100% of metaplastic thymomas (YAP1::MAML2), and 6% of B2 and B3 thymomas (MAML2::KMT2A); NUTM1 rearrangements in NUT carcinomas (most commonly BRD4::NUTM1); EWSR1 rearrangement in hyalinizing clear cell carcinoma (EWSR1::ATF1); and NTRK rearrangement in a thymoma (EIF4B::NTRK3). This review focuses on TET in which these fusion genes have been identified, their morphologic, immunophenotypic, and clinical characteristics and potential clinical implications of the fusion genes. Larger, multi-institutional, global studies are needed to further elucidate the molecular characteristics of these rare but sometimes very aggressive tumors in order to optimize patient management, provide patients with the opportunity to undergo targeted therapy and participate in clinical trials, and to elucidate the pathogenesis of these tumors.
proteins
2025-09-21 | PERM associated with thymic carcinoma with triple-autoantibody positivity: case report and literature review.
Progressive encephalomyelitis with rigidity and myoclonus (PERM) represents a severe Stiff-person syndrome (SPS) variant with brainstem and autonomic involvement. Although PERM is occasionally paraneoplastic-typically associated with antibodies such as anti-GAD, anti-GlyR, and anti-amphiphysin-its association with thymic carcinoma has not been previously described. To report a case of PERM associated with thymic carcinoma and triple autoantibody positivity in cerebrospinal fluid (CSF), and to review the literature on paraneoplastic and multiple-antibody PERM. A literature review of paraneoplastic and multiple-antibody PERM cases was conducted in English. The case report follows CARE guidelines. A 47-year-old Mexican-mestizo female patient was diagnosed with PERM secondary to stage IIIB thymic carcinoma. Brain MRI revealed hyperintensities in the mesial temporal and orbitofrontal regions. CSF analysis showed anti-GAD65, anti-amphiphysin, and anti-titin antibodies. Intravenous immunoglobulin therapy resulted in marked clinical improvement. The literature review demonstrated wide clinical and immunological heterogeneity. Most patients were female, typically presenting in later adulthood. Anti-GAD was the most frequent antibody, often coexisting with others in thymoma-associated cases. Presentations were consistently severe, often involving neuropsychiatric, autonomic, and brainstem symptoms, despite frequently unremarkable MRI findings. Coexisting antibodies in paraneoplastic cases were linked to more aggressive disease, while anti-GlyR positivity was associated with milder presentations and better treatment response. Early immunotherapy was generally beneficial. This case highlights the need for timely oncologic and immunologic evaluation in atypical SPS presentations and underscores the therapeutic importance of early diagnosis and treatment.
2025-06-23 | Patient With Advanced Aggressive B2 Thymoma Achieved Positive Outcomes Post CAP-Endostar Combination Therapy.
This case report features a patient with an invasive thymoma. The patient presented with an anterior mediastinal mass that invaded the left brachiocephalic trunk vein, resulting in the formation of a carcinoma thrombus in the right atrium, superior vena cava, left brachiocephalic trunk vein, and left internal jugular vein (Masaoka stage IV). No indication for surgery was assessed by surgical consultation. After six cycles of chemotherapy and chest radiotherapy, the tumor size decreased from 72.43 to 24 mm, showing a significant improvement in patient efficacy. After a follow-up of 50 months, the patient remained well, without local recurrence or distal metastasis, and maintained a partial response (PR).
2025-06-12 | An update on the therapeutic options for metastatic thymomas and thymic carcinomas.
Thymic epithelial tumors are rare cancers originating from the thymus, with an annual incidence of 0.13 per 100,000 persons. Therefore, the standard of care was approved primarily based on the results of single-arm phase II trials. If the disease is resectable and localized, a multidisciplinary treatment combining surgical resection, radiotherapy, and pharmacotherapy should be considered. Pharmacotherapy is the mainstay of treatment for metastatic and recurrent diseases. This review delineates the distinct difference in treatment strategies of chemotherapy in patients with thymomas and thymic carcinomas. Thymomas typically respond to a cisplatin and anthracyclines, often supplemented with steroids, whereas thymic carcinomas, which do not typically involve anthracyclines as key drugs, are treated with platinum-based doublet chemotherapy. Lenvatinib has emerged as a pivotal key drug for refractory thymic carcinoma. In addition, single-agent cytotoxic chemotherapy, molecular targeted therapies, and immune checkpoint inhibitors is considered as key drugs for thymic carcinomas. Current research is focused on developing novel therapeutics such as antibody-drug conjugates (ADCs), angiogenesis inhibitors, multi-kinase inhibitors, and further immune checkpoint inhibitors, expanding the prospects for pharmacotherapy in thymic malignancies.
2025-04-26 | Correction of changes in lung tissue during complex treatment malignant thymoma
Thymoma is a rare malignancy, clinical signs are non-specific, and the disease may be asymptomatic for a long time. The aim of this report is to highlight the complexity of treatment of a patient with IV stage of the disease. Research methods such as observation and analysis of data obtained as a result of correction of complications of antitumour treatment of the patient were used in the work. According to the results obtained, the multimodal approach to the complex treatment of patients with locally advanced process makes it advisable to observe for post-radiation and postoperative complications and their correction.
2025-03-24 | Pure White Cell Aplasia, an Exceedingly Rare Complication of a Thymoma, and Immune Reconstitution Following Bone Marrow Recovery.
Thymoma-associated pure white cell aplasia (PWCA), characterized by agranulocytosis with absent myeloid precursors in the bone marrow in the setting of preserved erythropoiesis and megakaryopoiesis, is exceedingly rare, with only a few cases reported in the literature. We present a case of type-B2-thymoma-associated PWCA and immune reconstitution following marrow recovery. A 75-year-old woman was incidentally found to have a concomitant mediastinal mass and peripheral leukopenia with absent granulocytes and monocytes. Bone marrow assessment was notable for a hypocellular marrow (<10%) with absent granulopoiesis and monopoiesis. Chest CT demonstrated a large lobulated anterior mediastinal mass, for which the patient underwent a video-assisted thoracoscopic thymectomy. Pathological evaluation of the mediastinal mass specimen revealed a type B2 thymoma. A tentative diagnosis of thymoma-associated PWCA was made, and the patient was started on cyclosporine/granulocyte-colony stimulating factor (G-CSF)/filgrastim therapy. Despite promising marrow recovery, she developed several comorbidities and had a leukemoid reaction, provoking concern for immune reconstitution following prolonged neutropenia and subsequent treatment. She passed away on post-operative day 15, and the results of a post-mortem bone marrow examination were consistent with granulocytic hyperplasia. This case of thymoma-associated PWCA heightens awareness regarding this entity, providing a note of caution regarding the possibility of immune reconstitution following treatment and marrow recovery.
small molecules
2026-09-25 | Fulminant immune checkpoint inhibitor-associated myositis presenting with concurrent myocardial injury and secondary cardiogenic shock in a patient with thymoma: a case report and literature review.
Immune checkpoint inhibitor (ICI)-associated toxicities are uncommon but may rapidly progress to cardiogenic shock and death. Patients with thymoma are considered particularly vulnerable to severe immune-related adverse events because thymic malignancy is closely associated with impaired central immune tolerance and autoimmune dysregulation. We report a 34-year-old man with stage IV type B2 thymoma who developed initial myalgia and fatigue approximately 15 days after the most recent pembrolizumab-containing treatment cycle and progressed to fulminant ICI-associated myositis with respiratory failure and secondary cardiogenic shock by day 19. He presented with severe immune-mediated myositis, concurrent myocardial injury, left ventricular systolic dysfunction, cardiogenic shock, metabolic acidosis, acute kidney injury, acute liver injury, coagulopathy, and respiratory failure. Coronary angiography excluded obstructive coronary disease, and microbiological and virological investigations did not identify an infectious cause. Endomyocardial biopsy and cardiac magnetic resonance imaging were not feasible because of profound hemodynamic instability, VA-ECMO support, and coagulopathy. The patient was treated with early venoarterial extracorporeal membrane oxygenation (VA-ECMO), high-dose methylprednisolone, intravenous immunoglobulin, continuous renal replacement therapy, mechanical ventilation, and comprehensive organ support. Cardiac function improved from a left ventricular ejection fraction of 25% to 51%, VA-ECMO was discontinued on hospital day 7, and the patient survived to discharge. This case and a focused literature review suggest that thymoma-associated ICI myositis with secondary cardiac dysfunction may represent a high-risk phenotype characterized by early onset, overlap neuromuscular toxicity, severe hemodynamic compromise, and potential reversibility when early immunosuppression and advanced circulatory support are implemented.
2026-09-20 | Invasive thymoma with rapid response to cisplatin, doxorubicin and cyclophosphamide (PAC) chemotherapy, after an early postoperative recurrence-a case report.
Thymomas generally exhibit indolent growth and local progression, with extrathoracic metastases being rare. Recurrence typically occurs months or years after surgical resection. We herein present a rare case of thymoma exhibiting rapid postoperative recurrence and abdominal lymph node metastasis, which showed a dramatic response to chemotherapy. A 66-year-old female was referred to our hospital for breast cancer treatment. A preoperative computed tomography (CT) scan coincidentally revealed a 7.5 cm anterior mediastinal tumor, suspected to be invading the pericardium and left lung. Extended thymothymectomy with partial resection of the left lung and pericardium was performed. Intraoperatively, no pleural dissemination was observed, and pleural effusion cytology was negative for malignant cells. The pathology was Type AB thymoma, Masaoka stage III [tumor, node, metastasis (TNM) 8th edition: pT3N0M0, Stage IIIA; TNM 9th edition: pT2N0M0, Stage II], with microscopically positive (R1) margins; thus, postoperative radiotherapy was planned. On postoperative day (POD) 18, she presented with dyspnea and massive left pleural effusion; after repeated thoracocentesis, the effusion recurred, and the patient was readmitted for continuous drainage. On POD 43, a CT scan showed a massive lesion along the left thoracic wall adjacent to the pericardium, with multiple small nodes in the left lung and two enlarged left gastric lymph nodes. A CT-guided needle biopsy of the thoracic wall performed on POD 47 confirmed recurrent thymoma. The patient received chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (PAC), with biochemical evidence of rapid tumor lysis that did not meet formal tumor lysis syndrome criteria. Chest X-ray on day 3 of chemotherapy showed near-complete resolution of the thoracic lesions, and a complete response, including normalization of the abdominal lymph nodes, was achieved after four courses of PAC. Serial follow-up imaging has shown no evidence of recurrence for at least 18 months. This case illustrates the diagnostic complexity of thymoma, including atypical radiological and pathological features together with an unusually aggressive early recurrence. Incomplete resection can lead to early recurrence and progression, and clinicians must remain vigilant for such atypical courses. The tumor nonetheless proved highly sensitive to chemotherapy, underscoring the importance of prompt systemic treatment intervention when recurrence occurs.
2026-09-20 | Narrative review: locally advanced thymoma-do we really need induction therapy before extended resection?
Locally advanced thymoma remains a challenging condition in which complete tumour clearance may require extended surgical resection. Induction therapy, including chemotherapy or chemoradiotherapy, is used in selected patients to improve resectability; however, the evidence supporting its routine use remains limited. This narrative review evaluates the role of induction therapy before extended resection, with particular attention to patient selection, resectability assessment, and multidisciplinary decision-making. A structured narrative review was conducted using PubMed/MEDLINE, supplemented by manual screening of reference lists from relevant articles, reviews, registry analyses, and guideline documents. The original search covered the period from January 1990 to April 2026 and was updated on 21 June 2026 during revision. Search terms included combinations of "thymoma", "thymic epithelial tumours", "locally advanced", "induction therapy", "neoadjuvant treatment", "preoperative chemotherapy", "chemoradiotherapy", "resectability", "borderline resectable", and "extended resection". English-language clinical studies, systematic and narrative reviews, registry analyses, and international guidelines were considered. The available evidence is largely derived from retrospective, heterogeneous studies, often including mixed populations of thymoma and thymic carcinoma. Platinum-based regimens can achieve radiologic response rates of approximately 50-70%, but no prospective or randomised data demonstrate a clear survival advantage over upfront surgery in clearly resectable thymoma. Induction therapy may provide practical advantages in selected anatomically complex or borderline-resectable cases, including tumour bulk reduction, improved operative planning, and potential facilitation of margin-negative resection. However, radiologic response does not necessarily indicate true pathologic downstaging or reduced need for en bloc resection. Current evidence therefore supports a selective, rather than routine, use of induction therapy following multidisciplinary assessment. Extended surgical resection remains the standard of care when complete resection appears achievable upfront. Current evidence is insufficient to support routine induction therapy in clearly resectable locally advanced thymoma, although induction treatment remains appropriate in selected borderline-resectable cases in which preoperative therapy may improve the likelihood or quality of complete resection. Further prospective and collaborative studies are needed to refine patient selection and clarify its role.
2026-09-20 | Very late recurrence of thymoma after 14 years: an International Thymic Malignancy Interest Group Tumor Board case report from a Turkish multidisciplinary team.
Thymomas are generally slow-growing tumors with a favorable prognosis; however, late recurrences have been well documented in the literature and may occur many years after complete (R0) resection. In this report, the multimodal management of a patient who experienced recurrence 14 years after surgery is presented as discussed during the multidisciplinary International Thymic Malignancy Interest Group (ITMIG) Tumor Board meeting on 17 October 2025. An 18-year-old female patient underwent median sternotomy in 2006 for resection of a 15.5-cm type B1 thymoma. Histopathological examination revealed microscopic transcapsular invasion with negative surgical margins, and adjuvant therapy was not recommended at that time. In 2020, progressive myasthenic symptoms led to re-evaluation, and imaging demonstrated multifocal right pleural recurrence with suspected involvement of the inferior vena cava and hepatic interface. Fine-needle aspiration biopsy confirmed recurrent World Health Organization (WHO) type B1 thymoma. Because complete resection was considered unlikely, the patient received cisplatin/etoposide chemotherapy followed by definitive chemoradiotherapy, achieving major radiologic response and disease stability. In 2024, after progression of a paravertebral recurrent lesion, salvage surgery was performed via right thoracotomy, including wedge resection, pleurectomy, mediastinal lymph node dissection, and intraoperative hyperthermic intrathoracic chemotherapy. The patient has since remained disease-free on continued surveillance. In thymic epithelial tumors with increased risk of recurrence, multimodal treatment strategies may improve long-term outcomes. This case highlights that very late recurrence may occur even after R0 resection and supports lifelong surveillance. Long-term follow-up should include periodic contrast-enhanced thoracic computed tomography, with magnetic resonance imaging considered in younger patients to reduce cumulative radiation exposure.
2026-09-13 | Robotic Resection With Hyperthermic Intrathoracic Perfusion Chemotherapy for Thymoma Recurrence.
Thymoma recurrence with pleural dissemination remains a therapeutic challenge, often requiring multimodal treatment strategies. Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (HITHOC) has emerged as a promising approach for selected patients; however, reports using minimally invasive robotic platforms are limited. We present the case of a 41-year-old woman with pleural and lymph node recurrence of type AB thymoma 3 years after robotic extended thymectomy. The patient underwent robotic-assisted cytoreductive surgery, including complete parietal pleurectomy and resection of pleural, pericardial, and subaortic lymph node lesions, followed by HITHOC with cisplatin and doxorubicin. The procedure was performed safely, with no major perioperative complications. The patient was discharged after 7 days and remained disease-free at 2-year follow-up. This case highlights the feasibility, safety, and potential oncological benefits of combining robotic cytoreductive surgery with HITHOC in the management of recurrent thymoma with pleural involvement. This minimally invasive multimodal strategy may represent a valuable option for carefully selected patients, although further studies with larger cohorts and longer follow-up are warranted.
cell therapies
2026-04-21 | Left brachiocephalic vein replacement and superior vena cava reconstruction with aortic homograft for thymic carcinoma.
Advanced intrathoracic tumours pose a significant challenge for thoracic surgeons because of the possible involvement of adjacent vital organs and major mediastinal vessels. The most effective therapeutic option for resectable thymic carcinomas is currently represented by complete surgical asportation en bloc with adjacent infiltrated structures to achieve more effective oncological outcomes. Vascular reconstruction, when required, is traditionally performed using prosthetic conduits; however, vascular homografts represent a potential alternative with several surgical and clinical advantages. We report a case of a large thymic carcinoma with mediastinal vessel invasion successfully treated by surgical resection and vascular reconstruction using an aortic homograft.
2026-03-14 | When Central Tolerance Fails: Thymic Malignancies at the Intersection of Cancer Immunity and Autoimmunity.
Thymic malignancies are rare cancers arising from thymic epithelial cells and are characterized by a highly diverse clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent associations with autoimmune syndromes. Although the clinical, immunological, and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumor staging and histological grading in shaping autoimmunity burden and infection risk. In this narrative review, we synthesize contemporary clinical, immunological, and morphologic evidence linking thymic architecture and selection defects to the spectrum of paraneoplastic autoimmunity (MG, pure red cell aplasia, Good's syndrome) and to infectious vulnerability. We further appraise emerging therapeutic strategies, including immune checkpoint inhibition and adoptive cellular approaches, through a patient-stratified lens, emphasizing efficacy signals, immune-related adverse events, and practical considerations for selection and monitoring. We conclude by highlighting priorities for future investigation, including refining autoantibody signatures; mapping thymic microenvironments that drive tolerance failure, and prospectively evaluating stratified immunotherapeutic regimens that balance benefit with immune-mediated risk.
2025-02-20 | Advanced thymic epithelial tumour resection: vascular resection and reconstruction strategy.
Thymic epithelial tumors (TETs) represent the predominant primary malignancy of the anterior mediastinum, often necessitating complex surgical interventions due to their invasive nature. The prognosis of advanced TET relies significantly on achieving complete resection with microscopically clear margins (R0). This frequently entails resection and reconstruction of major vascular structures like the superior vena cava (SVC) and brachiocephalic veins, and in some cases, extra pleural pneumonectomy (EPP). The aim of the study is to interrogate our series of advanced TET resections. We analysed our experience with vascular resection and reconstruction in 14 patients with advanced stage III/IV TET undergoing extensive resection post-neoadjuvant chemotherapy. A comprehensive preoperative evaluation was performed, including computed tomography (CT), positron emission tomography (PET), biopsy, and exercise testing. We describe our surgical approach and the details of our series. From 2015 to 2023, 31 patients underwent surgery for advanced TET at our centre, with major vessel reconstruction performed in 14 cases. This included resection of SVC and innominate veins with subsequent reconstruction using polytetrafluoroethylene (PTFE) grafts. The median operative time was 350 minutes, with a median blood loss of 1,300 mL. Cardiopulmonary bypass (CPB) was required in 2 cases. The rate of R0 resection was 78.6%, with a recurrence rate of 14.3% at a median follow-up of 1,700 days. Postoperative complications occurred in 42.9% of patients, with an in-hospital mortality rate of 7.1%. Multi-disciplinary management, meticulous preoperative planning, and advanced surgical techniques are essential for the successful treatment of advanced TET. Complex vascular resections should be reserved for high-volume centres to optimize outcomes.
2025-01-08 | Multimodal management and complete resection of invasive Type B3 thymoma with vascular reconstruction: a case report.
Thymomas and thymic carcinomas are rare anterior mediastinal tumours, accounting for 0.2-1.5% of all cancers. Surgical resection is key to treatment, though invasion of surrounding structures like great vessels can complicate this. This case report details the management of a type B3 thymoma (T4 N0 M0) in a 41-year-old male. A 41-year-old male presented with myasthenic symptoms and was diagnosed with a large thymic mass involving the brachiocephalic vein and superior vena cava. After 4 cycles of neoadjuvant chemotherapy, partial resection was performed, followed by radiotherapy. Residual disease led to a second surgery, during which tumour resection and vascular reconstruction using cardiopulmonary bypass were successfully completed. Postoperative recovery was uneventful. Complete resection, including re-resection, when necessary, is crucial for improved outcomes in thymoma patients. Even with great vessel invasion, aggressive surgery, coupled with chemotherapy and vascular reconstruction, can achieve good survival outcomes. Multimodal management, including chemotherapy, complete resection, and vascular reconstruction, offers the best prognosis for invasive thymomas, even with great vessel involvement.
2024-08-04 | Cell Culture Models for Translational Research on Thymomas and Thymic Carcinomas: Current Status and Future Perspectives
Cell culture model systems are fundamental tools for studying cancer biology and identifying therapeutic vulnerabilities in a controlled environment. TET cells are notoriously difficult to culture, with only a few permanent cell lines available. The optimal conditions and requirements for the ex vivo establishment and permanent expansion of TET cells have not been systematically studied, and it is currently unknown whether different TET subtypes require different culture conditions or specific supplements. The few permanent cell lines available represent only type AB thymomas and thymic carcinomas, while attempts to propagate tumor cells derived from type B thymomas so far have been frustrated. It is conceivable that epithelial cells in type B thymomas are critically dependent on their interaction with immature T cells or their three-dimensional scaffold. Extensive studies leading to validated cell culture protocols would be highly desirable and a major advance in the field. Alternative methods such as tumor cell organoid models, patient-derived xenografts, or tissue slices have been sporadically used in TETs, but their specific contributions and advantages remain to be shown.
antibodies
2026-09-24 | Navigating coexisting autoimmunity and immunodeficiency in thymoma: a case report of TAMA, Good's syndrome, and myasthenic crisis.
The coexistence of thymoma-associated multiorgan autoimmunity (TAMA) and Good's syndrome creates a challenging clinical scenario in which autoimmunity and profound immunodeficiency occur simultaneously. Here, we report a 37-year-old female with invasive WHO Type B3 thymoma and myasthenia gravis (MG) who developed progressive erythroderma-like skin lesions with graft-versus-host disease-like interface dermatitis. Immunological evaluation revealed marked hypogammaglobulinemia, absent circulating B cells, reduced CD4+ T cells, and an inverted CD4+/CD8+ ratio. During a subsequent myasthenic crisis, severe immune dysfunction and active pulmonary infection were already present. Because conventional rapid immunomodulatory options were limited, efgartigimod and eculizumab were administered sequentially. The pulmonary infection continued to progress, and the patient ultimately died. This case highlights the importance of immune and infection risk assessment before potent immunomodulatory therapy.
2026-09-23 | Ivonescimab plus chemotherapy as first-line treatment for advanced thymic carcinoma: preliminary results of a phase II trial with biomarker analyses.
Thymic carcinoma is a rare, aggressive malignancy with limited treatment options. First-line platinum-based chemotherapy yields response rates below 40%, and immune checkpoint inhibitors have shown inconsistent efficacy. Ivonescimab, a programmed cell death protein 1/vascular endothelial growth factor (PD-1/VEGF) bispecific antibody, may enhance antitumor activity through dual blockade.This single-center, phase II trial enrolled patients with stage IVb, treatment-naïve thymic carcinoma. Patients received ivonescimab (20 mg/kg) plus paclitaxel (175 mg/m²) and carboplatin (area under the curve 5) every 3 weeks for four to six cycles, followed by ivonescimab maintenance. The primary endpoint was objective response rate (ORR) . Secondary endpoints included disease control rate (DCR) and safety. Biomarker analyses were exploratory.Between January 2025 and April 2026, seven patients were enrolled (median age 61 years; 71% male; 71% squamous). Five had evaluable tissue next-generation sequencing and six had transcriptomic data. After median follow-up of 6.4 months, the preliminary ORR was 85.7% (6/7; 95% CI 42.1% to 99.6%) and DCR 100%. The 6-month progression-free survival (PFS) and overall survival (OS) rates were both 100% (two and four patients at risk for PFS and OS, respectively). The only PFS event occurred at 15.7 months in a patient who discontinued treatment due to adverse events (AEs). Grade ≥3 treatment-related AEs occurred in 57.1% (mainly neutropenia, 42.9%); grade ≥3 immune-related AEs in 14.3%. No treatment-related deaths occurred. All tumors were microsatellite-stable with low mutational burden. Deep responders (≥50% reduction) showed a lower exploratory myeloid-derived suppressor cell-related gene-expression score (nominal p=0.10, exact Mann-Whitney U test). Baseline blood CD4+/CD8+ ratio was lower in deep responders and remained stable during treatment, vs an increase in others (nominal p=0.057). Tumorous CXCL1 expression showed an exploratory positive correlation with the CD4+/CD8+ ratio (R=0.84, nominal p=0.035, n=6).First-line ivonescimab plus paclitaxel-carboplatin showed promising preliminary antitumor activity and manageable safety in advanced thymic carcinoma. The peripheral blood CD4+/CD8+ ratio showed an exploratory association with depth of response and warrants prospective evaluation in the complete cohort and independent validation.Trial registration numberChiCTR2400094398.
2026-09-11 | Immune checkpoint inhibitors in thymic epithelial tumors: current evidence, immune-related toxicity, and perioperative considerations-a narrative review.
Thymic epithelial tumors (TETs) are rare mediastinal malignancies with unique immunobiological features related to thymic immune tolerance. Although immune checkpoint inhibitors (ICIs) have shown clinical activity, especially in thymic carcinoma, their use is limited by frequent and sometimes severe immune-related adverse events (irAEs), particularly in thymoma. This review summarizes current evidence on the efficacy, toxicity, biomarkers, and perioperative implications of ICIs in TETs. A narrative review was conducted using PubMed, Web of Science, and Embase for English-language studies on ICIs in TETs published from database inception to September 2025. Reference lists of relevant articles and guideline papers were also manually screened. Prospective trials, retrospective cohorts, guideline papers, and key mechanistic studies were prioritized, with emphasis on histology-specific efficacy, irAEs, biomarkers, and perioperative application. Current evidence suggests that ICIs have more consistent antitumor activity in thymic carcinoma than in thymoma. In contrast, thymoma carries a substantially higher risk of severe early irAEs, particularly myocarditis, myositis, and myasthenia gravis overlap syndromes. Biomarkers such as programmed death-ligand 1 (PD-L1) expression and immune-related signatures remain promising but are not yet sufficiently validated for routine patient selection. Perioperative immunotherapy is an emerging strategy, but current evidence remains limited and safety concerns are significant. ICIs represent a promising treatment option for selected patients with advanced TETs, particularly thymic carcinoma, but their clinical use remains restricted by toxicity and limited evidence. Future progress will depend on better risk stratification, biomarker-guided selection, and safer multidisciplinary integration.
2026-08-04 | Case Report: Efgartigimod: a beacon of hope for overlapping stiff-person syndrome and myasthenia gravis following thymoma.
The coexistence of stiff person syndrome (SPS) and myasthenia gravis (MG) is exceptionally rare, with fewer than 20 cases reported to date. Thymoma has been identified in a substantial proportion of these patients, suggesting a potential shared autoimmune mechanism. We report a 43-year-old woman who initially presented with progressive limb stiffness, painful muscle spasms, and gait impairment. She was diagnosed with SPS based on positive anti-glutamic acid decarboxylase (GAD) antibodies and characteristic electromyographic findings. Her symptoms improved after immunotherapy but relapsed following corticosteroid withdrawal. Four years later, she developed fluctuating limb weakness and ptosis and was subsequently diagnosed with anti-acetylcholine receptor antibody-positive MG associated with type B2 thymoma. Following thymectomy and postoperative radiotherapy, COVID-19 infection precipitated a myasthenic crisis requiring intensive care support. Conventional treatments, including plasma exchange, intravenous immunoglobulin, corticosteroids, and rituximab, failed to achieve satisfactory clinical improvement. In contrast, treatment with efgartigimod resulted in marked recovery of respiratory and motor function. During follow-up through December 2025, no recurrence of SPS symptoms or MG exacerbation was observed. This case highlights the complex association among SPS, MG, and thymoma and supports the possibility that thymoma may contribute to the development of multiple autoimmune neurological disorders. Furthermore, efgartigimod may represent a promising therapeutic option for refractory thymoma-associated MG in patients with overlapping SPS and MG. Long-term surveillance for thymoma and additional autoimmune manifestations should be considered in patients with SPS.
2026-07-28 | Palliative Systemic Therapy in Advanced Thymic Epithelial Tumors in 2026-A Narrative Review.
Palliative systemic therapy for advanced thymic epithelial tumors (TET) is challenging due to scarce evidence and biological heterogeneity. Scientific discussion, as in this review, is limited to cross-trial comparisons of small, non-randomized studies. Platinum-based combination chemotherapy is the standard first-line treatment. Here, we challenge the addition of anthracyclines to platinum in thymoma. We critically appraise new combinations with antiangiogenic drugs and immune checkpoint inhibitors (ICI) in thymic carcinoma and their implications for therapy sequences. We review the data on classic genomics-based targeted therapy that does not benefit most patients and explore established and upcoming biomarkers including KIT and HER2. Finally, we discuss investigational therapies like anti-TROP2 antibody-drug conjugates and proteasome inhibitors, as well as topics and design of future research.
other
2025-12-07 | Unveiling CCR9 and CCL13 as immune biomarkers and therapeutic targets in thymoma.
This study employed bioinformatics to identify immune-related diagnostic and therapeutic target genes in thymoma, offering a theoretical foundation for clinical diagnosis and treatment of the disease. In this study, machine learning techniques were employed to identify and validate potential biomarkers, leading to the construction of a diagnostic nomogram. Immune infiltration analysis was subsequently conducted to explore the relationships between these biomarkers and immune cell populations. Finally, the findings were validated through RT-qPCR and Western blotting experiments, ensuring the robustness of the results. Three critical biomarkers were selected for thymoma, with CCR9 and CCL13 confirmed as the final biomarkers through ROC analysis, both demonstrating AUC values exceeding 0.7. Immune infiltration analysis revealed significant differences in 14 types of immune cells between the thymoma and control groups, highlighting a strong association between macrophages and the biomarkers. A nomogram for thymoma was constructed using these 2 biomarkers, exhibiting robust performance. Ultimately, validation experiments using RT-qPCR and Western blotting confirmed the consistency of CCR9 and CCLI3 expression with the bioinformatics results. CCR9 and CCL13 were identified in this study as immune-related biomarkers associated with thymoma, which might provide a theoretical foundation for the development of targeted gene therapies.
2025-02-14 | Targeting vaccines to dendritic cells by mimicking the processing and presentation of antigens in xenotransplant rejection.
Targeting the delivery of vaccines to dendritic cells (DCs) is challenging. Here we show that, by mimicking the fast and strong antigen processing and presentation that occurs during the rejection of xenotransplanted tissue, xenogeneic cell membrane-derived vesicles exposing tissue-specific antibodies can be leveraged to deliver peptide antigens and mRNA-encoded antigens to DCs. In mice with murine melanoma and murine thymoma, xenogeneic vesicles encapsulating a tumour-derived antigenic peptide or coated on lipid nanoparticles encapsulating an mRNA coding for a tumour antigen elicited potent tumour-specific T-cell responses that inhibited tumour growth. Mice immunized with xenogeneic vesicle-coated lipid nanoparticles encapsulating an mRNA encoding for the spike protein of severe acute respiratory syndrome coronavirus 2 elicited titres of anti-spike receptor-binding domain immunoglobulin G and of neutralizing antibodies that were approximately 32-fold and 6-fold, respectively, those elicited by a commercialized mRNA-lipid nanoparticle vaccine. The advantages of mimicking the biological recognition between immunoglobulin G on xenogeneic vesicles and fragment crystallizable receptors on DCs may justify the assessment of the safety risks of using animal-derived biological products in humans.
2024-10-18 | Enhancing preventive and therapeutic cancer vaccine efficacy through biotherapeutic ligand-associated extracellular vesicles.
Extracellular vesicles (EVs), secreted by almost all living cells, have gained significant attention for their role in intercellular communication and their potential as versatile carriers for biotherapeutics. However, the clinical translation of EV-based therapies faces significant challenges, primarily due to the lack of efficient methods for loading biotherapeutic agents into EVs. This study introduces a simple, reproducible strategy for the simultaneous incorporation of various biotherapeutics within EVs. The process is gentle and preserves the essential physicochemical and biological characteristics of EVs, thereby protecting labile ligands from premature degradation and elimination. The binding and uptake efficiency of EVs by target cells reached approximately 97 % within 24 h of incubation. Administration of EVs loaded with oligodeoxynucleotides (ODN) resulted in a 4-fold increase in IFNγ+ CD4+ T cells and a 5-fold increase in IFNγ+ CD8+ T cells in the spleens and lymph nodes. Additionally, the co-administration of EVs with ODN and ovalbumin (OVA) induced elevated Th1-biased antibody responses and antigen-specific cytotoxic T-cell responses, providing long-lasting complete protection in 60 % of mice against T-cell thymoma challenge. Furthermore, EVs associated with three different ligands (OVA, CpG-ODN, and α-GalCer) effectively regressed established murine melanoma and significantly improved survival rates in mice. This study presents a powerful and promising approach to overcoming the limitations of EV-based cancer vaccines, advancing the development of effective cancer immunotherapies. SUMMARY: Immunization with EVs that are co-associated with antigen and biotherapeutic cargo through a lyophilization-based technique elicits potent anti-cancer immunity.
2024-06-03 | Single-Cell Sequencing Illuminates Thymic Development: An Updated Framework for Understanding Thymic Epithelial Tumors.
Thymic epithelial tumors (TETs) are rare tumors for which treatment options are limited. The ongoing need for improved systemic therapies reflects a limited understanding of tumor biology as well as the normal thymus. The essential role of the thymus in adaptive immunity is largely effected by its epithelial compartment, which directs thymocyte (T-cell) differentiation and immunologic self-tolerance. With aging, the thymus undergoes involution whereby epithelial tissue is replaced by adipose and other connective tissue, decreasing immature T-cell production. Against this natural drive toward involution, a fraction of thymuses will instead undergo oncologic transformation, leading to the formation of TETs, including thymoma and thymic carcinoma. The rarity of these tumors restricts investigation of the mechanisms of tumorigenesis and development of rational treatment options. To this end, the development of technologies which allow deep molecular profiling of individual tumor cells permits a new window through which to view normal thymic development and contrast the malignant changes that result in oncogenic transformation. In this review, we describe the findings of recent illuminating studies on the diversity of cell types within the epithelial compartment through thymic differentiation and aging. We contextualize these findings around important unanswered questions regarding the spectrum of known somatic tumor alterations, cell of origin, and tumor heterogeneity. The perspectives informed by single-cell molecular profiling offer new approaches to clinical and basic investigation of thymic epithelial tumors, with the potential to accelerate development of improved therapeutic strategies to address ongoing unmet needs in these rare tumors.
2023-12-09 | The Role of Gene Fusions in Thymic Epithelial Tumors.
Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional studies have identified a number of interesting molecular aberrations in TET, including gene fusions in a subset of these tumors. These gene fusions can aid in the diagnosis, shed light on the pathogenesis of a subset of tumors, and potentially may provide patients with the opportunity to undergo targeted therapy or participation in clinical trials. Gene fusions that have been identified in TET include MAML2 rearrangements in 50% to 56% of mucoepidermoid carcinomas (MAML2::CRTC1), 77% to 100% of metaplastic thymomas (YAP1::MAML2), and 6% of B2 and B3 thymomas (MAML2::KMT2A); NUTM1 rearrangements in NUT carcinomas (most commonly BRD4::NUTM1); EWSR1 rearrangement in hyalinizing clear cell carcinoma (EWSR1::ATF1); and NTRK rearrangement in a thymoma (EIF4B::NTRK3). This review focuses on TET in which these fusion genes have been identified, their morphologic, immunophenotypic, and clinical characteristics and potential clinical implications of the fusion genes. Larger, multi-institutional, global studies are needed to further elucidate the molecular characteristics of these rare but sometimes very aggressive tumors in order to optimize patient management, provide patients with the opportunity to undergo targeted therapy and participate in clinical trials, and to elucidate the pathogenesis of these tumors.
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Drug Discovery Landscape
3 orphan drug designations for Thymoma.
3 orphan drug designations for Thymoma.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Bimiralisib | small molecules | EMA | Maxia Strategies-Europe Limited | |
Belinostat | small molecules | EMA | Onxeo DK, Filial af Onxeo S.A., Frankrig | |
Milciclib maleate | small molecules | EMA | Tiziana Life Sciences Public |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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