Severe West Nile virus and Sars-CoV-2 infections in a patient with thymoma and anti-type I IFN antibodies.

The current study aimed to investigate determinants of severity in a previously healthy patient who experienced two life-threatening infections, from West Nile Virus and SARS-CoV2. During COVID19 hospitalization he was diagnosed with a thymoma, retrospectively identified as already present at the time of WNV infection. Heterozygosity for p.Pro554Ser in the TLR3 gene, which increases susceptibility to severe COVID-19, and homozygosity for CCR5 c.554_585del, associated to severe WNV infection, were found. Neutralizing anti-IFN-α and anti-IFN-ω auto-antibodies were detected, likely induced by the underlying thymoma and increasing susceptibility to both severe COVID-19 pneumonia and West Nile encephalitis.

Lymphocyte-Directed Immunomodulation Remits Thymoma-Associated Autoimmune Pneumonitis.

BACKGROUND: Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome. OBJECTIVES: To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation. METHODS: Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab. RESULTS: Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12-36 months following treatment initiation. CONCLUSION: Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma.

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.

Thymic gene expression analysis reveals a potential link between HIF-1A and Th17/Treg imbalance in thymoma associated myasthenia gravis.

Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T (Treg) cells have been demonstrated in subgroups of MG. On the other hand, hypoxia-inducible factor 1 (HIF-1) has been shown to regulate the Th17/Treg balance by inducing Th17 differentiation while attenuating Treg development. To identify the underlying mechanisms of different thymic pathologies in MG development, we evaluated thymic samples from thymoma-associated myasthenia gravis (TAMG), MG with hyperplasia (TFH-MG) and thymoma without MG (TOMA) patients. Differential gene expression analysis revealed that TAMG and TFH-MG cells are associated with different functional pathways. A higher RORC/FOXP3 ratio provided evidence for Th17/Treg imbalance in TAMG potentially related to increased HIF1A. The hypoxic microenvironment in thymoma may be a driver of TAMG by increasing HIF1A. These findings may lead to new therapeutic approaches targeting HIF1A in the development of TAMG.

The Prognostic Role of the Number of Involved Structures in Thymic Epithelial Tumors: Results from the ESTS Database.

BACKGROUND: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection. METHODS: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis. RESULTS: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 95% confidence interval [CI] 1.010-6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021-1.905; p = 0.036). CONCLUSIONS: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification.

Deep learning for risk stratification of thymoma pathological subtypes based on preoperative CT images.

OBJECTIVES: This study aims to develop an innovative, deep model for thymoma risk stratification using preoperative CT images. Current algorithms predominantly focus on radiomic features or 2D deep features and require manual tumor segmentation by radiologists, limiting their practical applicability. METHODS: The deep model was trained and tested on a dataset comprising CT images from 147 patients (82 female; mean age, 54 years ± 10) who underwent surgical resection and received subsequent pathological confirmation. The eligible participants were divided into a training cohort (117 patients) and a testing cohort (30 patients) based on the CT scan time. The model consists of two stages: 3D tumor segmentation and risk stratification. The radiomic model and deep model (2D) were constructed for comparative analysis. Model performance was evaluated through dice coefficient, area under the curve (AUC), and accuracy. RESULTS: In both the training and testing cohorts, the deep model demonstrated better performance in differentiating thymoma risk, boasting AUCs of 0.998 and 0.893 respectively. This was compared to the radiomic model (AUCs of 0.773 and 0.769) and deep model (2D) (AUCs of 0.981 and 0.760). Notably, the deep model was capable of simultaneously identifying lesions, segmenting the region of interest (ROI), and differentiating the risk of thymoma on arterial phase CT images. Its diagnostic prowess outperformed that of the baseline model. CONCLUSIONS: The deep model has the potential to serve as an innovative decision-making tool, assisting on clinical prognosis evaluation and the discernment of suitable treatments for different thymoma pathological subtypes. KEY POINTS: • This study incorporated both tumor segmentation and risk stratification. • The deep model, using clinical and 3D deep features, effectively predicted thymoma risk. • The deep model improved AUCs by 16.1pt and 17.5pt compared to radiomic model and deep model (2D) respectively.

Clinical study of thoracoscopic assisted different surgical approaches for early thymoma: a meta-analysis.

OBJECTIVE: The efficacy and safety of subxiphoid thoracoscopic thymectomy (SVATS) for early thymoma are unknown. The purposes of this meta-analysis were to evaluate the effectiveness and safety of SVATS for early thymoma, to compare it with unilateral intercostal approach video thoracoscopic surgery (IVATS) thymectomy, and to investigate the clinical efficacy of modified subxiphoid thoracoscopic thymectomy (MSVATS) for early anterior mediastinal thymoma. METHODS: Original articles describing subxiphoid and unilateral intercostal approaches for thoracoscopic thymectomy to treat early thymoma published up to March 2023 were searched from PubMed, Embase, and the Cochrane Library. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and analyzed for heterogeneity. Clinical data were retrospectively collected from all Masaoka stage I and II thymoma patients who underwent modified subxiphoid and unilateral intercostal approach thoracoscopic thymectomies between September 2020 and March 2023. The operative time, intraoperative bleeding, postoperative drainage, extubation time, postoperative hospital stay, postoperative visual analog pain score (VAS), and postoperative complications were compared, and the clinical advantages of the modified subxiphoid approach for early-stage anterior mediastinal thymoma were analyzed. RESULTS: A total of 1607 cases were included in the seven studies in this paper. Of these, 591 cases underwent SVATS thymectomies, and 1016 cases underwent IVATS thymectomies. SVATS thymectomy was compared with IVATS thymectomy in terms of age (SMD = - 0.09, 95% CI: -0.20 to - 0.03, I2 = 20%, p = 0.13), body mass index (BMI; SMD = - 0.10, 95% CI: -0.21 to - 0.01, I2 = 0%, p = 0.08), thymoma size (SMD = - 0.01, 95% CI: -0.01, I2 = 0%, p = 0.08), operative time (SMD = - 0.70, 95% CI: -1.43-0.03, I2 = 97%, p = 0.06), intraoperative bleeding (SMD = - 0.30. 95% CI: -0.66-0.06, I2 = 89%, p = 0.10), time to extubation (SMD = - 0.34, 95%CI: -0.73-0.05, I2 = 91%, p = 0.09), postoperative hospital stay (SMD = - 0.40, 95% CI: -0.93-0.12, I2 = 93%, p = 0.13), and postoperative complications (odds ratio [OR] = 0.94, 95% CI: 0.42-2.12, I2 = 57%, p = 0.88), which were not statistically significantly different between the SVATS and IVATS groups. However, the postoperative drainage in the SVATS group was less than that in the IVATS group (SMD = - 0.43, 95%CI: -0.84 to - 0.02, I2 = 88%, p = 0.04), and the difference was statistically significant. More importantly, the postoperative VAS was lower in the SVATS group on days 1 (SMD = - 1.73, 95%CI: -2.27 to - 1.19, I2 = 93%, p < 0.00001), 3 (SMD = - 1.88, 95%CI: -2.84 to - 0.81, I2 = 97%, p = 0.0005), and 7 (SMD = - 1.18, 95%CI: -2.28 to - 0.08, I2 = 97%, p = 0.04) than in the IVATS group, and these differences were statistically significant. A total of 117 patients undergoing thoracoscopic thymectomy for early thymoma in the Department of Thoracic Surgery of the Second Hospital of Jilin University were retrospectively collected and included in the analysis, for which a modified subxiphoid approach was used in 42 cases and a unilateral intercostal approach was used in 75 cases. The differences between the two groups (MSVATS vs. IVATS) in general clinical characteristics such as age, sex, tumor diameter, Masaoka stage, Word Health Organization (WHO) stage, and intraoperative and postoperative conditions, including operative time, postoperative drainage, extubation time, postoperative hospital stay, and postoperative complication rates, were not statistically significant (p > 0.05), while BMI, intraoperative bleeding, and VAS on postoperative days 1, 3, and 7 were all statistically significant (p < 0.05) in the MSVATS group compared with the IVATS group. CONCLUSION: The meta-analysis showed that the conventional subxiphoid approach was superior in terms of postoperative drainage and postoperative VAS pain scores compared with the unilateral intercostal approach. Moreover, the modified subxiphoid approach had significant advantages in intraoperative bleeding and postoperative VAS pain scores compared with the unilateral intercostal approach. These results indicate that MSVATS can provide more convenient operation conditions, a better pleural cavity view, and a more complete thymectomy in the treatment of early thymoma, indicating that is a safe and feasible minimally invasive surgical method.

Germinal centers are associated with postthymectomy myasthenia gravis in patients with thymoma.

BACKGROUND AND PURPOSE: Germinal centers (GCs) can be observed in the thymic tissues of patients with thymoma-associated myasthenia gravis (MG). Although an association between thymic GCs and MG has been suggested, it is unknown whether the presence of GCs could predict the development of MG after the resection of thymoma, known as postthymectomy MG. METHODS: We conducted a retrospective analysis of previously nonmyasthenic patients who underwent surgical removal of the thymoma. All available thymic tissue slides were rereviewed by a pathologist to assess for GCs. Patients were classified into GC-positive and GC-negative groups based on the presence of GCs. The incidence of postthymectomy MG was compared between the two groups, and the risk factors for postthymectomy MG were assessed. RESULTS: Of the 196 previously nonmyasthenic patients who underwent thymoma resection, 21 were GC-positive, whereas 175 were GC-negative. Postthymectomy MG developed in 11 (5.6%) patients and showed a higher incidence in the GC-positive group than in the GC-negative group (33.3% vs. 2.3%, p < 0.001). No postoperative radiotherapy and the presence of GCs were risk factors for postthymectomy MG in the univariate analysis. In multivariate analysis, invasive thymoma (hazard ratio [HR] = 9.835, 95% confidence interval [CI] = 1.358-105.372), postoperative radiotherapy (HR = 0.160, 95% CI = 0.029-0.893), and presence of GCs (HR = 15.834, 95% CI = 3.742-67.000) were significantly associated with postthymectomy MG. CONCLUSIONS: Thymic GCs may be a significant risk factor for postthymectomy MG. Even in patients with thymoma who do not show clinical symptoms of MG, postthymectomy MG should be considered, especially if thymic GCs are observed.

Ectopic cervical thymoma in myasthenia gravis: a case report.

BACKGROUND: Ectopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG). CASE PRESENTATION: We report a case of myasthenia gravis with an ectopic thymoma in the neck, whose myasthenic symptoms significantly improved after complete removal of the mass. A 55-year-old woman with generalized myasthenia gravis (MG) experienced worsening neuromuscular weakness after abruptly discontinuing pyridostigmine. Testing revealed acetylcholine receptor-antibody (AChR-Ab) positivity and a cervical mass initially thought to be thyroid or parathyroid was identified as a thymoma, type A. Post-surgery and radiation therapy, her myasthenic symptoms improved significantly with less prednisone and pyridostigmine requirements over time and no need for additional immunotherapies. CONCLUSIONS: Diagnosing ECTs is challenging due to rarity, atypical locations, and inconclusive fine needle aspiration cytology (FNAC) results, often misinterpreted as thyroid or parathyroid lesions. As proper management of patients with MG, including thymectomy, offers favorable clinical outcomes such as significant improvement in myasthenic complaints and reduced immunosuppressive medication requirements, clinicians should be vigilant of the ectopic locations of thymomas to ensure timely diagnosis and intervention.

Taste disorders and alopecia in myasthenia gravis.

BACKGROUND: Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. METHODS: We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. RESULTS: Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. CONCLUSION: Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.

Unique association of anti-GABAA receptor encephalitis and myasthenia gravis in a patient with type A thymoma.

Association between anti-GABAAR encephalitis and myasthenia gravis is extremely rare with few reported cases. Herein, we report a case of a female patient diagnosed with anti-GABAAR encephalitis and thymoma at the first admission. She was administered glucocorticoids for long-term immunotherapy, and thymectomy with biopsy demonstrated a type A thymoma. After 4 months, the symptoms of encephalitis were relieved, but she then developed post-thymectomy myasthenia gravis with anti-AChR and anti-titin dual positivity. Antibodies to connective tissue (anti-ANA, anti-PCNA) and those characteristics of paraneoplastic syndrome (anti-Ma2/Ta) were also positive. She received oral glucocorticoids and tacrolimus as immunosuppressive therapy, and myasthenic symptoms were stable during a 2-year follow-up. Our case revealed that anti-GABAAR encephalitis and myasthenia gravis can appear in patient with type A thymoma at different periods, which alerts physicians to take long-term follow-up for anti-GABAAR encephalitis with thymoma, even after thymectomy. Concurrent positivity for more than one antibody after thymectomy is rarely observed, and their contribution to the clinical course and treatment decision remains to be further investigated.

Steroid-resistant minimal change nephrotic syndrome associated with thymoma treated effectively with rituximab following thymectomy and cyclosporine: a case report.

BACKGROUND: Minimal change nephrotic syndrome (MCNS) can be complicated by thymoma; however, no standard therapy for thymoma-associated MCNS has yet been established. We herein describe a case of steroid-resistant MCNS associated with thymoma, treated effectively with rituximab. CASE PRESENTATION: A 71-year-old Japanese man was referred to our department with severe proteinuria (20 g/gCr). Renal biopsy showed minimal change disease and computed tomography revealed an anterior mediastinal mass. Based on these findings, he was diagnosed with thymoma-associated MCNS. He was treated with oral prednisolone (50 mg/day) and cyclosporine, and underwent thymectomy and plasma exchange. However, no improvement in proteinuria was observed. He therefore received intravenous rituximab 500 mg, resulting in a marked decrease in proteinuria from 5328 to 336 mg/day after 1 week. CONCLUSIONS: This case suggests that rituximab might be an effective therapy in patients with steroid-resistant MCNS associated with thymoma.

Mark Wick contributions to pathology of the mediastinum.

Mark Wick made a wide range of contributions to the field of mediastinal pathology. Early papers amplified the spectrum of neuroendocrine carcinomas of the thymus and brought attention to the aggressive nature of this tumor, also highlighting the occurrence of coexisting carcinoid tumor and small cell carcinoma of this organ. The controversial issue of thymoma classification was addressed in several papers and editorial comments, while also reporting a case of metastatic thymoma. A series of thymic carcinomas as well a report on the unusual clear cell variant bear his name as one of the authors. He summarized the topic of mediastinal cyst in a review published in 2005. Sarcomas arising in mediastinal germ cell tumors were also within the purview of his interests, with a publication of series of seven cases. He reviewed the topic of inflammatory myofibroblastic tumor of the heart and added a case to the existing literature. Two books dedicated to different aspect of mediastinal pathology also carry his name in the front cover in association with Drs Taazelar in one and Marchevsky in the other.

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

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

Ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis: a case report.

BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.

Re-exploration of prognosis in type B thymomas: establishment of a predictive nomogram model.

OBJECTIVE: To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model. METHODS: A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression. RESULTS: A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1-128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p < 0.001). No benefits of postoperative radiotherapy (PORT) were observed in patients with advanced stage and non-R0 resection (p = 0.114 and 0.284, respectively). CONCLUSION: The best treatment strategy for type B thymoma is the detection and achievement of R0 resection as early as possible. Long-term follow-up is necessary, especially for patients with advanced Masaoka stage and who have not achieved R0 resection. No prognostic benefits were observed for PORT.

Clinicopathological predictors of postoperative long-term myasthenic status in resected thymoma with myasthenia gravis.

PURPOSE: Surgical patients with thymoma and myasthenia gravis (MG) must have their MG status and oncological outcomes critically monitored. We aimed to identify clinicopathological predictors of the postoperative MG status. METHODS: We conducted a retrospective review of 40 consecutive surgical patients with MG-related thymomas between 2002 and 2020. The quantitative myasthenia gravis score (QMGS) and Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS) were used to evaluate postoperative MG status. RESULTS: All patients underwent extended total thymectomy. The most common WHO type was type B2 (32%), while 65% of patients had type B1-B3 and 35% had type A-AB thymomas. Eleven patients (28%) achieved controlled MG status in MGFA-PIS 6 months after surgery. This controlled status was observed more frequently in type A-AB than in B1-B3 (57% vs. 12%, p = 0.007). In a multivariate analysis, WHO type (A-AB or B1-B3) was an independent predictor of worsening episodes of MG based on the QMGS (Type B1-B3, hazard ratio: 3.23, 95% confidence interval: 1.12-9.25). At the last follow-up, 23 patients (58%) achieved controlled MG status. The 5-year overall survival rate of all patients was 93.7%. CONCLUSION: The WHO type of thymoma is an informative predictor of postoperative MG status in patients with MG-related thymoma.

The role of calcification in predicting invasion of thymoma to adjacent organs.

PURPOSE: Thoracoscopic procedures such as video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracoscopic surgery (RATS) have gained popularity for the treatment of thymoma. Accurate preoperative assessments of tumor invasion are crucial to identifying the appropriate surgical approach. Although imaging techniques have been used to predict invasion, a quantifiable method is still needed in clinical practice. METHODS: The ubjects of this retrospective study were 226 patients with thymoma who underwent surgery at our hospital. Clinicopathological data, tumor staging, and recurrence rates were analyzed. Calcification identified through computed tomography (CT) defined the "calcified group" as having a long diameter of ≥ 5 mm. Statistical analyses were performed to assess relationships and survival outcomes. RESULTS: The calcified group had higher Masaoka and World Health Organization classification than the noncalcified group, with significantly higher organ invasion rates. The calcified group also had remarkably higher recurrence rates. CONCLUSION: Thymoma calcification appears to correlate with increased invasiveness and recurrence rates, suggesting its potential as a predictor of tumor stage and prognosis. Despite its retrospective nature and inherent limitations, this study highlights the potential clinical significance of calcification in the surgical planning and prognostication of patients with thymoma.

Lobulated tumor contour as a predictor of preoperative tumor invasion of the lung or pericardium in thymoma patients.

PURPOSE: Preoperative investigations to detect invasion to neighboring organs are important for deciding on the most appropriate surgical approach for thymoma. We evaluated preoperative computed tomography (CT) findings in thymoma patients to identify the CT features associated with tumor invasion. METHODS: Clinicopathologic information on 193 patients who underwent surgical resection for thymoma at Chiba University Hospital between 2002 and 2016 was collected retrospectively. The surgical pathology identified invasion of thymoma in 35 patients: in the lung (n = 18), pericardium (n = 11), or both (n = 6). Contact lengths between the tumor contour and lung (CLTL) or pericardium (CLTP) were measured at the maximum section of the tumor on axial CT. Univariate and multivariate analyses were performed to analyze the relationship between pathological invasion of the lung or pericardium and the clinicopathologic features. RESULTS: The mean CLTL and CLTP were significantly longer in patients with invasion of the neighboring organs than in those without invasion. A lobulated tumor contour was identified in 95.6% of the patients with invasion of the neighboring organs. A multivariate analysis revealed that a lobulated tumor contour was significantly associated with both lung and pericardial invasion. CONCLUSIONS: A lobulated tumor contour was significantly associated with lung and/or pericardial invasion in thymoma patients.

Surgical resection of advanced intrathoracic tumors through a combination of the hemiclamshell and transmanubrial approaches.

PURPOSE: The hemiclamshell (HCS) approach provides a comprehensive view of the anterior mediastinum, whereas the transmanubrial osteomuscular sparing approach (TMA) allows sufficient exposure of the cervico-thoracic transition. We assessed the effectiveness and the outcomes of the combined HCS plus TMA approach to resect thoracic malignant tumors. METHODS: We reviewed five patients with thoracic malignant tumors invading the thoracic outlet who underwent surgery using an HCS and TMA approach between 2018 and 2021. RESULTS: The preoperative diagnosis was myxofibrosarcoma, lung cancer, thymic cancer, thymoma, and neurofibromatosis type1 in one patient each, respectively. Cardiovascular reconstruction was done on the aortic arch in two patients, on the descending aorta in one, and on the superior vena cava in one, combined with resection of the vagus nerve in three patients, of the phrenic nerve in two, and of vertebra in one, with overlap in some cases. The TMA was added because all patients required dissection of the periphery of the subclavian artery, and two had tumor extension to the neck. Macroscopic complete resection was achieved in four patients. There was no postoperative mortality. CONCLUSION: The combination of the HCS and TMA approaches at the same operation provides a comprehensive view of the mediastinum, lung, and cervico-thoracic transition and allows safe access to the thoracic great vessels and subclavian vessels.