Immunohistochemical characteristics of cytokeratin expression in epithelial type thymoma and thymic epithelial hyperplasia in F344 rats.

We have previously reported on thymomas in Wistar Hannover rats with medullary differentiation and revealed that two different cytokeratin (CK) immunohistochemical types of thymic epithelia (TE), CK18 and CK14, lead to the formation of cortical-medullary structures. In aged F344 rats, epithelial-type thymoma rarely occurs, and thymic epithelial hyperplasia is common. However, CK expression in these F344 rat lesions is unknown. We investigated three hyperplasia and four thymomas in F344 for histopathological features and CK18 and CK14 expression. Hyperplasia was characterized by an increase in tubular structures in the medulla. Thymomas were nodular in shape, with tubular structures similar to those observed in hyperplasia, along with irregular structures such as cord, papillary, and spindloid. Immunohistochemical analysis revealed that the tubular structures consisted of two layers: inner cuboidal-to-columnar TE and outer round-to-oval TE, positive for CK18 and CK14, respectively. The two-layer pattern was maintained to some extent in the irregular structures.

Unveiling Thymoma Typing Through Hyperspectral Imaging and Deep Learning.

Thymoma, a rare tumor from thymic epithelial cells, presents diagnostic challenges because of the subjective nature of traditional methods, leading to high false-negative rates and long diagnosis times. This study introduces a thymoma classification technique that integrates hyperspectral imaging with deep learning. We initially capture pathological slice images of thymoma using a hyperspectral camera and delineate regions of interest to extract spectral data. This data undergoes reflectance calibration and noise reduction. Subsequently, we transform the spectral data into two-dimensional images via the Gramian Angular Field (GAF) method. A variant residual network is then utilized to extract features and classify these images. Our results demonstrate that this model significantly enhances classification accuracy and efficiency, achieving an average accuracy of 95%. The method proves highly effective in automated thymoma diagnosis, optimizing data utilization, and feature representation learning.

Intrathyroidal Thymoma: A Diagnostic Challenge.

Intrathyroidal thymoma is a rare tumor that can be challenging to diagnose due to its unusual location and resemblance to more common thyroid conditions. We present the case of a 58-year-old woman with an incidentally discovered thyroid nodule during evaluation for an upper respiratory infection. Ultrasonography revealed an exophytic nodule in the left thyroid lobe, categorized as TR 3. Fine-needle aspiration cytology suggested a neoplastic process, leading to a left hemithyroidectomy. Histopathology confirmed a diagnosis of intrathyroidal thymoma, Type B2, with extensive necrosis, and immunohistochemistry validated the findings. This case underscores the diagnostic challenges of intrathyroidal thymoma, emphasizing its consideration in the differential diagnosis of atypical thyroid nodules. Despite the difficulties in preoperative identification, surgical resection and subsequent histopathological examination remain essential for a definitive diagnosis. The patient is currently under surveillance, and there is no evidence of residual thymic tissue or abnormalities in the remaining thyroid tissue.

Transdiaphragmatic extension of a thymoma invading the peritoneum and the spleen.

Thymoma, a rare tumor originating from thymic epithelial cells in the anterior mediastinum, presents various diagnostic and clinical challenges, particularly when exhibiting unusual invasive behaviors. We report a case involving a 66-year-old woman with progressive dyspnea and a dry cough, where a CT scan revealed a large, lobulated mass in the anterior mediastinum that had extended through the diaphragm into the abdominal cavity, infiltrating the pleura, spleen, and adjacent structures. Histopathological examination confirmed a type B2 thymoma, classified as T3N2M0 stage IV B. The case underscores the importance of early and accurate diagnosis, highlighting the need for a multidisciplinary approach involving radiologists, oncologists, and thoracic surgeons to manage such advanced thymoma cases. The unusual transdiaphragmatic extension into the peritoneum and spleen emphasizes the necessity of considering extensive local invasion in the staging and treatment planning of thymomas, which often necessitates a combination of chemotherapy and radiotherapy before potential surgical intervention.

Unusual presentation of cytomegalovirus and varicella-zoster virus infection in a patient with good's syndrome: A case report.

The co-infection of cutaneous cytomegalovirus (CMV) and varicella-zoster virus (VZV) is a rare occurrence, particularly in the context of Good's syndrome (GS). This report presents a unique case of a 56-year-old man with GS, characterized by a thymoma, who developed cutaneous CMV and VZV co-infections. We discuss the clinical characteristics, diagnostic process, and treatment of this uncommon manifestation. A 56-year-old man with a mediastinal mass identified as thymoma type A and pleural metastasis, presented with a three-week progressive, painful generalized skin lesions on his face, trunk, and extremities. Upon further examination, multiple extensive vesicles with reddened bases were distributed throughout all regions of his body, some exhibited hemorrhagic characteristics. The histopathologic assessment indicated a herpes virus infection and leukocytoclastic vasculitis. Additionally, Immunohistochemistry staining for CMV highlighted infected endothelial cells. The patient was diagnosed with disseminated cutaneous co-infection of CMV and VZV in the context of Good's syndrome. The patient responded well to a treatment regimen combining intravenous immunoglobulin (IVIG) and ganciclovir therapy, leading to the complete resolution of skin lesions. He was recommended prophylactic treatment and showed significant improvement upon follow-up, ultimately being discharged in a favorable clinical condition. By gaining a better understanding of this condition, healthcare professionals can improve their ability to recognize and treat Good's syndrome effectively. Early identification and effective treatment have a crucial role in enhancing the prognosis.

Differential diagnosis between low-risk and high-risk thymoma: Comparison of diagnostic performance of radiologists with and without deep learning model.

Background: There are few CT-based deep learning (DL) studies on thymoma according to the World Health Organization classification. Purpose: To develop a CT-based DL model to distinguish between low-risk and high-risk thymoma and to compare the diagnostic performance of radiologists with and without the DL model. Material and Methods: 159 patients with 160 thymomas were included. A fine-tuning VGG16 network model with Adam optimizer was used, followed by k-fold cross validation. The dataset consisted of three axial slices, including the maximum tumor size from the CT volume data. The data were augmented 50 times by rotation, zoom, shear, and horizontal/vertical flip. Three independent networks for the CT dataset were considered, and the result was determined by voting. Three radiologists independently diagnosed thymomas with and without the model. The area under the curve (AUC) of the diagnostic performance was compared using receiver operating characteristic analysis. Results: Accuracy of the DL model was 71.3%. Diagnostic performance of the radiologists was as follows: AUC and accuracy without the DL model, 0.61-0.68 and 61.9%-69.3%; and with the DL model, 0.66-0.69 and 68.1%-70.0%, respectively. AUC of the diagnostic performance showed no significant differences between radiologists with and without the DL model. The DL model tended to increase the diagnostic accuracy, but AUC was not significantly improved. Conclusion: Diagnostic performance of the DL was comparable to that of radiologists. The DL model assistance tended to increase diagnostic accuracy.

Thymoma with recurrent opportunistic infections-a case report.

Good's syndrome (GS) is a rare adult-onset thymoma associated with acquired combined B-cell and T-cell immunodeficiency. It has similarities with Common variable immunodeficiency (CVID) in terms of hypogammaglobulinemia and significant risk of invasive bacterial and opportunistic infections. We still have a long way to go in understanding the pathogenesis of Good's syndrome. Here, we describe a case of a middle-aged female with thymoma and recurrent opportunistic infections. Clinico-laboratory evaluation led to a diagnosis of GS and she showed good response to intravenous immunoglobulin. Clinicians should be aware that thymoma can precede the onset of immunodeficiency.

Case report: Multi-antibody-positive myasthenia gravis concomitant myositis associated with thymoma.

Myasthenia gravis (MG) and idiopathic inflammatory myopathy (IIM) are autoimmune diseases of the nervous system, and their main clinical manifestation is muscle weakness. The concurrent presence of both conditions in the same patient is clinically rare and easily missed. Here, we report the case of a 74-year-old woman who went to the doctor with fluctuating weakness of the limbs and muscle pain. By analyzing the patient's history and the results of repeated frequency electrical stimulation, chest computed tomography, thigh muscle magnetic resonance imaging, serum antibody detection, lymph node biopsy, etc., she was finally diagnosed with MG-concomitant IIM with squamous cell carcinoma of the thymus. Acetylcholine receptor antibody, titin antibody, ryanodine receptor antibody, anti-JO-1 antibody, and Ro-52 antibody tests were positive. MG-concomitant IIM is often associated with thymoma. The immunopathology mechanism may be different from that of pure MG or IIM, which needs further research.

Application of machine learning for the differentiation of thymomas and thymic cysts using deep transfer learning: A multi-center comparison of diagnostic performance based on different dimensional models.

OBJECTIVE: This study aimed to evaluate the feasibility and performance of deep transfer learning (DTL) networks with different types and dimensions in differentiating thymomas from thymic cysts in a retrospective cohort. MATERIALS AND METHODS: Based on chest-enhanced computed tomography (CT), the region of interest was delineated, and the maximum cross section of the lesion was selected as the input image. Five convolutional neural networks (CNNs) and Vision Transformer (ViT) were used to construct a 2D DTL model. The 2D model constructed by the maximum section (n) and the upper and lower layers (n - 1, n + 1) of the lesion was used for feature extraction, and the features were selected. The remaining features were pre-fused to construct a 2.5D model. The whole lesion image was selected for input and constructing a 3D model. RESULTS: In the 2D model, the area under curve (AUC) of Resnet50 was 0.950 in the training cohort and 0.907 in the internal validation cohort. In the 2.5D model, the AUCs of Vgg11 in the internal validation cohort and external validation cohort 1 were 0.937 and 0.965, respectively. The AUCs of Inception_v3 in the training cohort and external validation cohort 2 were 0.981 and 0.950, respectively. The AUC values of 3D_Resnet50 in the four cohorts were 0.987, 0.937, 0.938, and 0.905. CONCLUSIONS: The DTL model based on multiple different dimensions can be used as a highly sensitive and specific tool for the non-invasive differential diagnosis of thymomas and thymic cysts to assist clinicians in decision-making.

Diagnosis of a cystic lymphocyte-rich thymoma in a young cat.

Thymoma is one of the thymic epithelial tumors arising from the thymic epithelial cells of a variety of animal species including cat, cattle, dog, goat, horse, and pig. The cancer cells of thymoma are always localized within thymus. Feline thymoma was usually identified in the cranial mediastinum of elder cats. In this report, we present the full diagnostic characteristics of a young cat with a cranial mediastinal mass diagnosed as a cystic type B1 thymoma. A 3-year-old male neutered domestic short-haired cat was referred for further diagnosis due to the shortness of breath and pleural accumulation. One single cystic extra-pericardial mass was seen and the boundary between the mass and the surrounding tissue was clearly demarcated in three-view thoracic radiographs. Ultrasound showed pleural effusion and intra-thoracic mass. Pleural fluid biochemistry showed high level of triglycerides and complete blood count revealed the elevated number of basophils and high level of feline serum amyloid A (fSAA). Pleural effusion sediment cytology showed a large number of round cells, mainly small lymphocytes, as well as a moderate number of neutrophils and a small number of large lymphocytes. The high level of triglycerides in pleural fluid instead of serum and high level of fSAA seem to provide informative clues to the diagnosis of thymoma and are worthy of further investigation.

Subxiphoid video-assisted thoracoscopic extend thymectomy with sternal suspension for thymoma.

BACKGROUND: Thymoma is a primary tumor of the thymus, commonly located in the anterior mediastinum. Most thymomas are benign or low-grade malignant, but they can invade surrounding organs or metastasize. The primary treatment for thymoma is surgical resection. Traditional methods involve open thoracotomy, but it is traumatic, with slow recovery and many complications. In recent years, with the development of thoracoscopic techniques, thoracoscopic total thymectomy has gradually become the preferred method for small size thymomas due to its minimally invasive, safe, and effective. METHODS: This paper introduces a thoracoscopic extend thymectomy technique, the subxiphoid video-assisted thoracoscopic extend thymectomy with sternal suspension. This method involves placing hooks at the upper and lower ends of the sternum to suspend the sternum upward, increasing the thoracic cavity space and facilitating thoracoscopic operations. This research reviews the clinical data of 59 patients with early-stage thymomas treated with this technique at our center since 2020 and analyzes the perioperative therapeutic efficacy and safety. It also compares the outcomes with those of 17 patients who underwent thoracoscopic approaches. RESULTS: The results show that subxiphoid video-assisted thoracoscopic total thymectomy with sternal suspension is an innovative and effective surgical method, achieving the same tumor eradication as other thoracic surgeries. The flexible switching of observation ports provides a more comprehensive surgical field, reduces surgical trauma and complications, and improves the surgical outcomes and quality of life for patients.

Thymoma-Related Chest Pain and Dyspnea in a Middle-Aged Caucasian Female With Myasthenia Gravis and Good's Syndrome: A Case Report.

Thymomas are rare tumors originating from thymic tissue, often associated with various paraneoplastic syndromes that can pose significant clinical management challenges. Myasthenia gravis, one of the most common paraneoplastic syndromes linked to thymomas, is characterized by autoantibodies targeting the neuromuscular junction, leading to muscle weakness exacerbated by repetitive use. Good's syndrome, an adult-onset immunodeficiency associated with thymomas, results in hypogammaglobulinemia and susceptibility to opportunistic infections, which can be life-threatening. We present the case of a 57-year-old Caucasian female with no prior medical history, who presented with a three-month history of progressive chest pain, dyspnea, and muscle weakness. A computed tomography (CT) scan of the chest revealed an anterior mediastinal soft tissue mass. Upon admission, a diagnostic workup, including serum anti-acetylcholine receptor antibodies and electromyography, confirmed the diagnosis of myasthenia gravis. Immune studies revealed hypogammaglobulinemia, consistent with Good's syndrome. The patient underwent complete surgical resection of the thymoma and received intravenous immunoglobulin (IVIG) therapy. This case report highlights the rarity and clinical significance of concurrent myasthenia gravis and Good's syndrome as paraneoplastic manifestations secondary to thymoma. Given the incidence of thymoma-associated paraneoplastic syndromes, early recognition and intervention are crucial for optimal outcomes. Future research may further elucidate the mechanisms underlying these associations, guiding improved management strategies.

Identification of Potential Key Genes for the Comorbidity of Myasthenia Gravis With Thymoma by Integrated Bioinformatics Analysis and Machine Learning.

Background: Thymoma is a key risk factor for myasthenia gravis (MG). The purpose of our study was to investigate the potential key genes responsible for MG patients with thymoma. Methods: We obtained MG and thymoma dataset from GEO database. Differentially expressed genes (DEGs) were determined and functional enrichment analyses were conducted by R packages. Weighted gene co-expression network analysis (WGCNA) was used to screen out the crucial module genes related to thymoma. Candidate genes were obtained by integrating DEGs of MG and module genes. Subsequently, we identified several candidate key genes by machine learning for diagnosing MG patients with thymoma. The nomogram and receiver operating characteristics (ROC) curves were applied to assess the diagnostic value of candidate key genes. Finally, we investigated the infiltration of immunocytes and analyzed the relationship among key genes and immune cells. Results: We obtained 337 DEGs in MG dataset and 2150 DEGs in thymoma dataset. Biological function analyses indicated that DEGs of MG and thymoma were enriched in many common pathways. Black module (containing 207 genes) analyzed by WGCNA was considered as the most correlated with thymoma. Then, 12 candidate genes were identified by intersecting with MG DEGs and thymoma module genes as potential causes of thymoma-associated MG pathogenesis. Furthermore, five candidate key genes (JAM3, MS4A4A, MS4A6A, EGR1, and FOS) were screened out through integrating least absolute shrinkage and selection operator (LASSO) regression and Random forest (RF). The nomogram and ROC curves (area under the curve from 0.833 to 0.929) suggested all five candidate key genes had high diagnostic values. Finally, we found that five key genes and immune cell infiltrations presented varying degrees of correlation. Conclusions: Our study identified five key potential pathogenic genes that predisposed thymoma to the development of MG, which provided potential diagnostic biomarkers and promising therapeutic targets for MG patients with thymoma.

Association between Infection and Calculated Globulin Level among Patients with Thymic Epithelial Tumor.

Background: Thymic epithelial tumors (TETs) are uncommon malignancies uniquely associated with autoimmunity and immunodeficiency. Previous studies among patients with primary immunodeficiency diseases have shown that a low calculated globulin (CG) level, obtained by subtracting albumin from total protein level, is associated with infection risk. We investigated this association among patients with TET. Methods: A cross-sectional retrospective study was performed based on electronic medical records of patients with TET treated during 2002-2024 at a tertiary care institution. For each patient, their lowest CG level and the date of occurrence were identified. The incidence of serious infection requiring hospitalization during 6 months before and 6 months after the index date was recorded. Multivariable Poisson regression models were constructed. Results: Among 101 TET patients, 96 patients (95%) had the information available to derive at least one CG level. The median lowest CG level was 2.65 g/dL (range 1.0-4.2). There were 33 serious infection episodes. Pneumonia was the most prevalent type of infection in 52% of episodes. In a multivariable analysis, a CG level below 2.0 was independently associated with the prevalence of infection with a prevalence ratio of 6.18 (95% CI: 3.12-12.23, p < 0.001). Furthermore, thymectomy was significantly associated with infection. Conclusions: Among patients with TET, a low CG level was associated with an increased prevalence of serious infections. Our limited experiences suggest that it is feasible to derive the CG level for most patients during routine clinical care.

Constitutional Factors and Irradiation as Risk Factors for Thymoma: A European Case-Control Study.

Little is known about the aetiology of thymoma. This study aims to identify medical risk factors for thymoma as a systematic approach to new hypotheses on the aetiology of this disease. A European multi-centre case-control study was conducted from 1995 to 1997, including incident cases aged 35-69 years with thymoma. Altogether, we accepted 85 cases and 3350 controls, of which we interviewed 77 cases and 2071 population controls about constitutional factors, medical examinations, and former diseases. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated. Medical examinations with X-ray or radiotherapy performed >20 times at least one year before the thymoma diagnosis indicated a possible risk factor for thymoma (OR 1.58, 95% CI 0.93-2.69). Having the first radiotherapy treatment at least one year before the thymoma diagnosis yielded an OR for thymoma of 2.39; 95% CI (0.96-5.99), and if it was at least five years before, the OR for thymoma was 2.81; 95% CI (1.03-7.72). Having a red/auburn hair colour was associated with thymoma, (OR 3.6, 95% CI 1.4-9.5) whereas having pigmented skin was slightly associated with thymoma (OR 1.8, 95% CI 0.8-3.8). Over twenty instances of X-ray examinations or radiotherapy were identified as potential risk factors for thymoma, along with certain constitutional factors. The observed correlations between benign tumours and thymoma could stem from an inherent predisposition to tumour development or result from detection bias. Given that this is the initial analytical study examining medical risk factors for thymoma, all of the results should be approached with caution, acknowledging the possibility that some findings might be incidental.

Robotic-assisted versus video-assisted thoracoscopic surgery for thymic epithelial tumours, from the European Society of Thoracic Surgeons Database.

OBJECTIVES: Minimally invasive thymectomy is an accepted approach for early-stage thymic epithelial neoplasia, reducing pain and length of stay compared with open surgery. In this study, we compare robotic and video-assisted thymectomy to assess pathological resection status, overall and disease-free survival. METHODS: Data were retrieved from the European Society of Thoracic Surgeons prospectively maintained thymic database. Eighty-two international centres were invited to participate in the ESTS registry. Thirty-seven centres agreed to take part. We included all patients who had undergone complete thymectomy for malignancy through a minimally invasive approach and excluded patients in whom complete data were not available. RESULTS: Between October 2001 and May 2021, a total of 899 patients with thymic malignancy underwent minimal access surgical resection and were included in the study. A propensity matched analysis was conducted with interrogation of 732 patients. Median age was 55 years, and 408 (56%) patients were female. Propensity matched was performed with 1:1 matching for surgical approach (video assisted = 366, robot assisted = 366). Robot-assisted surgery conferred significantly lower odds of incomplete resection (R1; 0.203 95% CI 0.13-0.317; P < 0.001). However, there was no difference in terms of overall and disease-free survival between the 2 techniques. CONCLUSIONS: In this analysis, after adjusting for thymoma stage, the odds of incomplete surgical resection were higher in patients undergoing video-assisted surgery than robotic. However, there was no difference in overall or disease-free survival. With data maturation and increased follow-up, this would need repeat analysis and perhaps may provide more credence to the concept of a prospective randomized study to compare outcomes in thymic epithelial neoplasia by surgical approach with a standardized pathological work-up.

DNA methylation as a new tool for the differential diagnosis between T-LBL and lymphocyte-rich thymoma.

T-lymphoblastic lymphoma (T-LBL) and thymoma are two rare primary tumors of the thymus deriving either from T-cell precursors or from thymic epithelial cells, respectively. Some thymoma subtypes (AB, B1, and B2) display numerous reactive terminal deoxynucleotidyl transferase-positive (TdT+) T-cell precursors masking epithelial tumor cells. Therefore, the differential diagnosis between T-LBL and TdT+ T-lymphocyte-rich thymoma could be challenging, especially in the case of needle biopsy. To distinguish between T-LBL and thymoma-associated lymphoid proliferations, we analyzed the global DNA methylation using two different technologies, namely MeDIP array and EPIC array, in independent samples series [17 T-LBLs compared with one TdT+ lymphocyte-rich thymoma (B1 subtype) and three normal thymi, and seven lymphocyte-rich thymomas compared with 24 T-LBLs, respectively]. In unsupervised principal component analysis (PCA), T-LBL and thymoma samples clustered separately. We identified differentially methylated regions (DMRs) using MeDIP-array and EPIC-array datasets and nine overlapping genes between the two datasets considering the top 100 DMRs including ZIC1, TSHZ2, CDC42BPB, RBM24, C10orf53, and MACROD2. In order to explore the DNA methylation profiles in larger series, we defined a classifier based on these six differentially methylated gene promoters, developed an MS-MLPA assay, and demonstrated a significant differential methylation between thymomas (hypomethylated; n = 48) and T-LBLs (hypermethylated; n = 54) (methylation ratio median 0.03 versus 0.66, respectively; p < 0.0001), with MACROD2 methylation status the most discriminating. Using a machine learning strategy, we built a prediction model trained with the EPIC-array dataset and defined a cumulative score taking into account the weight of each feature. A score above or equal to 0.4 was predictive of T-LBL and conversely. Applied to the MS-MLPA dataset, this prediction model accurately predicted diagnoses of T-LBL and thymoma. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Thymoma With Myasthenia Gravis: A Study of Two Cases.

Thymoma is a rare, primary neoplasm of the thymus gland, commonly presenting in adults and associated with autoimmune diseases, most commonly myasthenia gravis (MG). Despite its generally indolent behavior, the variability in clinical presentation and potential for malignancy necessitates detailed evaluation and management. In this report, we present two cases: a 41-year-old male and a 39-year-old female, both of whom presented with a mediastinal mass with symptoms of myasthenia. Further investigation, including imaging and histopathological examination, confirmed the diagnosis of a type B2 thymoma and type B1 thymoma for the male and female patients, respectively. The patients underwent successful complete surgical resection of the masses, with the postoperative recovery being uneventful. They were monitored for signs of disease recurrence and associated autoimmune conditions during follow-up visits. This report underscores the importance of early detection and thorough clinical evaluation of thymoma, particularly in patients with associated paraneoplastic syndromes. Complete surgical resection remains the cornerstone of treatment, with adjuvant therapy tailored based on individual risk factors. Ongoing surveillance is crucial for identifying potential recurrences and associated conditions.

Stereotactic Ablative Radiation Therapy for Sacral Bone Metastasis in Recurrent Type A Thymoma: A Two-Year Follow-Up Demonstrating Pain Reduction and Local Control.

A 74-year-old Asian man presented with sacral bone metastasis-related pain caused by a metastatic thymoma. Computed tomography revealed an approximately 6-cm sacral mass, which was confirmed as a metastatic thymoma. The patient was referred to our department and underwent stereotactic ablative radiation therapy (SABR) using volumetric modulated arc therapy and received a total dose of 35 Gy in five fractions. One year after SABR, the sacral lesion had decreased in size, and the pain medication was reduced. After two years, the patient no longer required pain medication, indicating successful management of bone metastases in recurrent Type A Thymoma.