Myasthenic crisis associated with invasive thymoma successfully treated with ravulizumab: A case series.

This article aims to emphasize the importance of considering invasive thymoma in the differential diagnosis of mediastinal masses and highlights the critical role of timely surgical and oncological management in improving patient outcomes. We present the case of a 70-year-old woman who presented with signs of superior vena cava syndrome, including dyspnea, facial swelling, and fatigue. Advanced imaging and intraoperative findings revealed a large anterior mediastinal mass infiltrating the left brachiocephalic vein and superior vena cava, extending into both the right atrium and right ventricle. Surgical intervention was performed, and histopathological analysis confirmed B2 thymoma with a high Ki-67 proliferation index. Despite surgical intervention, the patient's condition deteriorated, and she ultimately succumbed to the disease. To the best of our knowledge, this is the first reported Bosnian case of B2 thymoma invading the brachiocephalic vein and superior vena cava and infiltrating both the right atrium and ventricle, causing superior vena cava syndrome. Despite their rarity, thymomas should always be considered in patients presenting with an enlarged mediastinum.

According to the guidelines for thymic tumors, surgical resection is recommended for clinical stage Ⅳ thymic epithelial tumors if completely resectable. A 38-year-old woman presented with fever, chest pain, and back pain. Computed tomography (CT) revealed a mediastinal tumor, which was diagnosed as thymoma type B3 through CT-guided biopsy. Intraoperatively, using 4K three-dimensional (3D) endoscopy, tumor invasion into the left upper lobe and pleural dissemination on the parietal pleura and diaphragm were observed. To preserve the possibility of future re-resection, operation was thoracoscopically performed and the tumor was removed, including partial resection of the left upper lobe. All visible pleural dissemination lesions were also resected, including part of the left diaphragm. The diaphragmatic defect was reconstructed using a Gore-Tex Patch. There is no established treatment strategy for thymoma with incidental pleural dissemination, and the 4K 3D endoscopy may contribute to the successful completion of such a complex operation.

BackgroundRobotic thymectomy has been accepted as a minimally invasive surgery for thymic epithelial tumors (TETs). Two main different approaches via subxiphoid or lateral access into anterior mediastinum have been reported. We review our standard procedure of robotic subxiphoid-optical thymectomy (RST) and aim to show the technical advantages of the fine surgical field of view in total thymectomy and combined resection of neighboring structures for malignant TETs.MethodsUnder spine position, only robotic scope is inserted via subxiphoid port without wound retractable device and Maryland-type dissectors are applied via bilateral 6th intercostal spaces on mid-clavicular line. An assist port is placed at the right 3rd intercostal space on anterior axillar line for artificial CO2 insufflation using AirSeal® (Figure 1). RST was indicated in 54 anterior mediastinal lesions and 28 TETs cases are investigated.ResultsPathological diagnoses are 26 thymomas [World Health Organization (WHO) type A 6, AB 7, B1 2, B2 8, B3 2, micronodular 1] and 2 thymic squamous cell carcinomas. Pathological staging was Masaoka stage I 6, II 20, III 2, and TNM stage I 26, II 1, III 1 patients. Myasthenia gravis (MG) is associated in 4 patients and 2 patients showed the elevation of serum anti-acetylcholine antibody without MG symptom. We experienced one Morvan syndrome and one Good syndrome with pure red cell aplasia cases. Total and subtotal thymectomies were performed in 27 and 1 patients, respectively. A combined resection of the innominate vein with the phrenic nerve was performed in a thymic carcinoma, and a partial pericardium resection was experienced in a B2 invasive thymoma. The median operative and console durations were 177 and 115 minutes, respectively. Neither open median sternotomy conversion nor transfusion was observed. One patient with pericardial resection showed post-pericardiotomy syndrome requiring readmission. No recurrent case was found in the short-term follow-up with the median of 2 years.ConclusionsRST is a safe and useful procedure applicable to extended resection for TETs. The excellent surgical field of view from subxiphoid scope and exquisite manipulation could realize the similar procedure to the median sternotomy approach.

BackgroundThymomas typically demonstrate an indolent growth pattern, showing a non-infiltrative behaviour and displacing adjacent structures, even when they reach a great size. However, high-grade thymomas may invade the capsule and directly extend into neighbouring organs. Airway involvement is exceedingly rare, with only a few cases documented in the literature.Case DescriptionWe report an uncommon case of invasive thymoma with endobronchial growth in a 75-year-old female. The patient initially presented with hemoptysis. Chest computed tomography imaging revealed a calcified mass in the anterior mediastinum with invasion of the left upper pulmonary lobe. Due to the extent of bronchial obstruction to a subsegmental bronchus of the left upper lobe, the radiological findings were initially interpreted as being most consistent with a primary lung neoplasm. Flexible bronchoscopy confirmed the presence of a polypoid lesion originating from the subsegmental bronchus of the left upper lobe (Figure 1). Histopathological examination of endobronchial biopsies revealed a B2 thymoma. Following multidisciplinary evaluation and staging investigations that excluded distant metastases, the patient was initially referred for neoadjuvant chemotherapy due to suspected involvement of the left main pulmonary artery and mediastinal lymph nodes. However, owing to significant toxicity after the first cycle, an upfront surgical approach was considered more appropriate. The patient subsequently underwent an en-bloc extended thymectomy with left upper lobectomy via a left posterolateral thoracotomy. Histopathological analysis of the surgical specimen confirmed tumour invasion into the pulmonary parenchyma and the bronchial lumen. All surgical margins, including the bronchial stump, were negative, and no lymph node metastases were identified [pT3N0, stage IIIa according to the 9th dedicated tumor-node-metastasis (TNM) classification, although the latest system does not yet consider bronchial involvement]. The postoperative course was uneventful, and the patient was discharged on postoperative day 6. She was subsequently enrolled in a pulmonary rehabilitation program to support recovery. Adjuvant radiotherapy targeting the anterior mediastinum was administered without complications. Follow-up bronchoscopies showed no abnormalities, and the patient remains disease-free on initial post-surgical surveillance imaging.ConclusionsIn conclusion, this rare case of invasive thymoma with endobronchial involvement emphasises the significance of prompt diagnosis, effective multidisciplinary treatment, and successful surgical management, leading to a favourable post-treatment outcome.

Although generally benign, thymomas have the potential to be malignant due to their tendency for local invasion and occasional development of distant metastases. They are characterized by infiltration and extension into adjacent structures, with metastasis typically confined to the pleura, pericardium, or diaphragm. In this case, a rare instance of invasive AB-type thymoma located in the anterior mediastinum is reported, which had invaded the superior vena cava and extended caudally into the right atrium. 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT clearly defined the size and characteristics of the lesion, providing valuable information for patient management.

A 47-year-old woman was diagnosed with invasive thymoma 13 years ago. She had undergone repeated surgeries, as well as chemotherapy and radiation therapy. Chemotherapy was discontinued after the patient developed normocytic anemia, which was unresponsive to repeated blood transfusions. Bone marrow biopsy results revealed pure red cell aplasia (PRCA). Cyclosporine treatment led to improvement in PRCA; however, the patient died 3 years later from an invasive pneumococcal infection. The onset of thymoma-associated PRCA remains unpredictable, and a significant delay may occur between the diagnosis of the two conditions.

PurposeThis study aimed to investigate retrospectively the feasibility of reducing the standard postoperative radiation therapy (PORT) dose of 45–50 Gy for locally invasive thymoma to shorten treatment duration and minimize side effects, while preserving disease-specific survival (DSS) and progression-free survival (PFS).Materials and MethodsBetween January 2016 and June 2022, 150 locally advanced thymoma patients underwent surgery followed by intensity-modulated radiation therapy, with a median follow-up of 40.8 months; the standard regimen was 45–50 Gy in 25 fractions (median biological effective dose [BED] 60 Gy), compared to a de-escalation regimen of 30–35 Gy in 10 fractions (median BED 47.25 Gy), with PFS as the primary endpoint, and overall survival (OS), DSS, and toxicity as secondary endpoints.ResultsNo significant differences were found between standard and de-escalation groups in 3-year PFS (p = 0.406), with both groups achieving 100% 3-year DSS; two deaths in the de-escalation group were due to double primary cancers. All locoregional recurrences occurred outside the radiation field. Factors including age, initial tumor size, myasthenia gravis, and pathological type showed no correlation with PFS or OS. No grade II toxicities occurred in the de-escalation group, whereas the standard group had three cases of grade II toxicity, specifically radiation pneumonitis.ConclusionRadiation dose de-escalation in locally advanced thymoma patients undergoing PORT showed comparable survival outcomes with reduced toxicity and shorter treatment duration, but requires longer follow-up to confirm efficacy and safety.

A 50year-old female was diagnosed with myasthenia gravis (MG) following aspiration pneumonia. Despite treatment with prednisolone (5mg/day) and intravenous immunoglobulin (IVIg), the bulbar palsy persisted. Additionally, chest CT revealed findings suggestive of invasive thymoma or thymic carcinoma, leading to a planned thymectomy with median sternotomy. This case presents a high-risk of myasthenic crisis due to thymoma-associated MG, persistent bulbar palsy, and the need for highly invasive surgery. Therefore, enhanced immunotherapy was required to prevent this crisis, and zilucoplan was chosen because of its rapid onset of action and compatibility with IVIg. Following the initiation of zilucoplan, there was prompt improvement in the symptoms of MG. Effective preoperative control of MG led to a good clinical course, with no significant postoperative myasthenic crisis or exacerbation of symptoms. This is the first report on the use of zilucoplan for the prevention of perioperative myasthenic crisis. (Received April 14, 2025; Accepted June 3, 2025, Published August 1, 2025).

Mastermind-like transcriptional coactivator (MAML) gene fusions have been documented in Thymic Epithelial Tumors (TETs). Specifically, lysine methyltransferase 2A (KMT2A)::MAML2 gene fusions are associated with type B2 and B3 thymomas. Here, we report for the first time a young patient with invasive type B3 thymoma harboring a novel KMT2A::MAML3 gene fusion. MAML3 and MAML2 are paralogues. In addition to the classic type B3 thymoma histology, this article documents intratumor heterogeneity, characterized by a trabecular and fascicular pattern, as well as areas of clear cells. Immunohistochemistry showed keratin positivity in tumor cells, while neuroendocrine markers were negative in trabecular regions. DNA-based next-generation sequencing failed to identify pathogenic variants, but RNA sequencing detected the KMT2A::MAML3 gene fusion. We compared the gene fusion sites of MAML2 and MAML3, focusing on exon 2, and found that they share similar functional protein domains. Moreover, the same domain appeared downstream of the KMT2A::MAML2 fusion protein. Therefore, we hypothesize that MAML3 gene fusions, like MAML2, lead to abnormal Notch signaling pathways and increase the invasive potential of certain thymoma subtypes. Our findings expand the genetic landscape of aggressive thymomas and offer new insights for molecular studies in TETs.

A young 22-year-old female patient with a known Thymoma, under yearly surveillance, presented with upper respiratory tract infection symptoms. She returned 3 weeks later with an unresolved cough. A chest radiograph demonstrated a retrocardiac homogenous opacity with another opacity obliterating the left cardiac margin. Further, two well-defined homogenous pleural-based opacities in the left upper and lower lung zones were noted. Further evaluation was done with a CT chest and PET scan. CT Thorax confirmed interval invasive features of previously seen left anterior mediastinal mass with direct involvement of pleura, pericardium, and multiple pulmonary nodules denoting invasive malignant thymoma. PET scan reported intensely hypermetabolic left pleural masses likely representing the patient’s thymoma. She underwent a guided tissue biopsy which concluded as Thymoma probably Type B2. She received chemotherapy, radiotherapy, and surgical resection of the lesion with full resolution of the lesion.

Abstract: Thymomas are rare tumors originating from the epithelial cells of the thymus, often associated with paraneoplastic syndromes such as myasthenia gravis. Despite its benign histology, thymomas can be very aggressive invading pleura, pericardium, and other mediastinal structures. Thymoma directly invading the superior vena cava (SVC) and causing obstructive symptoms is common but thymoma causing SVC obstruction by thrombus formation without invasion is rarely seen. Here, we present one such case of 36-year-old man presenting with features of SVC obstruction and later found to have anterior mediastinal mass, completely occluding bilateral internal jugular and SVC with multiple collaterals and histopathology confirmed Type A thymoma positive for PAN CK.

Good Syndrome From Invasive Thymoma Leading to GL-ILD

Minimally invasive large thymoma resection remains controversial given the paucity of long-term oncological outcomes. We described the recurrence and survival of patients with thymomas ≥ 5 cm resected robotically. Consecutive thymoma resections between January 2006 and December 2022 were reviewed. Thymic carcinoma/neuroendocrine tumors, induction therapy treatment, and Stage IV disease were excluded. For thymomas ≥ 5 cm, open versus robotic resections were compared. With robotic resections, thymomas ≥/< 5 cm were compared. The outcomes were freedom from recurrence (FFR) and overall survival (OS). There were 40 thymomas ≥ 5 cm (15 open and 25 robotic) and 52 robotic thymoma < 5 cm resections. Median follow-up was 5 years with 4 (4%) patients having recurrences and 5 (5%) demised. In thymomas ≥ 5 cm, patients were similar, except for higher comorbidities in the open cohort. Five-year FFR (p = 0.42) and OS (p = 0.34) were comparable. Patients with robotic resection of thymomas ≥/< 5 cm were similar, except those < 5 cm were more frequently Masaoka-Koga Stage II. Five-year FFR (p = 0.62) and OS (p = 0.62) were similar. Resectable large thymomas, ≥ 5 cm, can be approached robotically with similar recurrence and survival when compared to open or smaller robotic resections. In otherwise appropriate thymomas, considerations such as location and proximity to surrounding structures, over size alone, should guide the approach.

BackgroundThymomas typically exhibit local progression, with metastasis to abdominal lymph nodes being relatively rare. Recurrence of thymoma usually occurs months or years after surgical treatment. However, we present a case with rapid postoperative recurrence and metastasis to abdominal lymph nodes.Case DescriptionA 66-year-old female was referred to our hospital for treatment of breast cancer. A preoperative computed tomography (CT) scan revealed a 7.5 cm anterior mediastinal tumor, suspected to invade the pericardium and left lung. Extended thymothymectomy plus partial resection of the left lung, and pericardial resection and reconstruction was performed. There were no signs of pleural implants, and pleural effusion cytology was negative for malignant cells. The patient was discharged on post-operative day (POD) 9. The pathology was thymoma (AB type, Masaoka stage III), with microscopically positive margins, leading to a planned postoperative radiotherapy. On POD 18, the patient visited our outpatient clinic with dyspnea. An X-ray showed a large amount of left pleural effusion. After multiple times of removal by centesis, the effusion recurred, thus the patient was readmitted for continuous drainage. On POD 43, swelling of the left anterior chest wall was noticed. 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 massively enlarged abdominal lymph nodes. CT-guided needle biopsy performed on POD 47 confirmed recurrent thymoma. Cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy initiated on POD 57 induced clinical tumor lysis syndrome. Three days later, there were almost no signs of remaining thoracic lesions on the X-ray. A CT scan after 2 courses of PAC showed the disappearance of the pleural mass and normalization of the abdominal lymph nodes. Following four PAC courses, remaining pleural effusion disappeared, achieving a complete response.ConclusionsAlthough thymoma is generally considered less aggressive compared to thymic carcinoma, incomplete resection can lead to early recurrence and progression, as seen in this case. In cases of incomplete resection, efforts should be made to avoid missing the opportunity for postoperative radiotherapy or chemotherapy.

Long-term survival outcomes are crucial for accurately determining the effectiveness of treatment in an indolent disease like thymoma. We aimed to analyze the clinical findings in terms of survival and relapse patterns with a median follow up of 105 months (8.7 years) in patients with thymoma and myasthenia gravis who underwent minimally invasive surgery between 2002 and 2015. A total of 59 pathologically confirmed Masaoka Stage I and II thymoma patients with Myasthenia Gravis (MG) who underwent minimally invasive thymoma resection were included in this study. Primary aim of this study is to evaluate recurrences, overall and disease free survival in patients with a thymoma and MG in the long run. We also aimed to study the changes in Myasthenia Gravis medication during the follow-up. The mean age of the patients was 47.6 +/13.5 years. Seventeen patients were at Masaoka Stage I and 42 were at Masaoka Stage II. The median follow-up time was 105 months. The mean size of the tumor was 3.6 cm +/16.2 cm. Twenty-one patients (35%) received adjuvant radiotherapy. There was no postoperative mortality and median length of hospital stay was 4 days. Two patients developed recurrences both presented with pleural metastases. Eight patients died because of non-oncologic pathologies. 10-year disease free survival and overall survival rates were calculated to 96.6% and 86.4% respectively. The 10-year survival analysis and current myasthenic status of stage I-II thymoma patients with myasthenia gravis who underwent minimally invasive surgery demonstrate that these procedures are both safe and effective.

Thymoma is often associated with other diseases, including autoimmune diseases and endocrine disorders. Crohn's disease is a nonspecific inflammatory disease and is considered an immune-mediated disorder; However, the coincidence of thymoma and Crohn's disease is rare. We report the observation of a 63-year-old woman with invasive thymoma and Crohn's disease. Following radio-chemotherapy, the digestive symptoms disappeared.

Rituximab (RTX) is a monoclonal antibody that has been increasingly used in the treatment of myasthenia gravis (MG). In most studies, the therapeutic protocol of RTX has been similar to that adopted for B cell lymphoma, with an increasing number of studies aimed at exploring the efficacy of low-dose RTX in MG. However, the beneficial effects of low-dose RTX in MG remain a subject of critical debate. This study was conducted following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Two reviewers (Xishuai Yang and Bingxia Li) independently conducted searches across multiple databases, including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). A meta-analysis, utilizing representative forest plots, was performed to assess "Improved clinical status" and changes in the Quantitative Myasthenia Gravis (QMG) score before and after treatment. A total of 17 studies involving 292 patients were included in the meta-analysis. A noticeable improvement in clinical status was observed in 91% of patients at the final follow-up after therapy (95% CI: 84-96%, P < 0.001). The QMG score showed a significant reduction following the treatment, with a standardized mean difference (SMD) of -1.69 (95% CI: -2.21 to -1.16, Z = 6.29, P < 0.001). In the acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG) group, 90% of patients achieved improved clinical status (95% CI: 80-97%, P < 0.001) and the QMG score significantly decreased after low-dose RTX treatment, with an SMD of -1.51 (95% CI: -0.80 to -2.21, Z = 4.50, P < 0.001). In the muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) group, 97% of patients achieved improved clinical status (95% CI: 89-100%, P < 0.001). The QMG score also significantly decreased following low-dose RTX treatment, with an SMD of -2.31 (95% CI: -2.99 to -1.62, Z = 6.60, P < 0.001). Adverse effects were reported in 29 out of 207 patients (14%, including infusion reactions in 22 patients (10.1%), infections in three patients (1.45%), cytopenia in two patients (0.96%), eosinophilia in one patient (0.48%), and hemiplegia in one patient (0.48%). Additionally, one patient (0.48%) succumbed to complications from invasive thymoma. Our meta-analysis shows that low-dose RTX is both effective and safe for treating MG. PROSPERO, identifier: CRD42024509951.

Thymic epithelial tumors (TETs), including thymomas and thymic cancers, are relatively rare malignancies originating from the thymus. Although complete surgical resection is the cornerstone of treatment for these tumors, the optimal management strategy for locally advanced cases remains uncertain. Neoadjuvant therapies, with their potential to improve the likelihood of complete resection, are promising, particularly in marginally operable cases. However, the current evidence supporting this approach is lacking. This review of the existing literature on the efficacy of induction therapy followed by surgical resection for stage III or IV locally advanced TETs aimed to provide an up-to-date perspective and highlighting directions for future clinical research. PubMed was searched using the keywords "surgery," "survival", "thymoma", "thymic cancer", and "induction therapy". Relevant articles including case series, retrospective studies, prospective studies, and review articles were reviewed and selected for this comprehensive narrative review. This review included primarily revealed retrospective studies and a limited number of prospective phase II trials on induction therapy followed by surgery for stage III or IV locally advanced TETs. No randomized phase III studies were identified, indicating that a comprehensive evaluation of the benefits of induction therapy on overall survival (OS) has not yet been conducted. Induction therapies for both invasive thymoma and thymic cancer included chemotherapy, radiotherapy, and chemoradiotherapy, with anthracycline-based combination chemotherapies being the primary option. For exclusively invasive thymomas, the median rate of complete surgical resection and the 5-year OS rate were reported as 76% and 85%, respectively. Literature focusing on induction therapy for TETs, which includes both thymoma and thymic cancers, indicates that the rates of complete resection and 5-year OS are 76% and 70%, respectively. Our narrative review of retrospective and prospective studies highlighted promising long-term OS rates in patients with advanced TETs who underwent induction therapy followed by surgical resection. These findings support this multimodal treatment strategy in selected patients with stage III and IV TETs.

Kiosk 3Q-TA-09 - Rare Case of Cardiac Invasive Metastatic Thymoma Utilizing High Accuracy CMR Tissue Characterization Techniques