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Aims: Thymic carcinoma and atypical thymoma (WHO type B3 thymoma) are unusual tumours the separation of which may be challenging in small biopsies. Both tumours consist of epithelioid tumour cells that share similar morphology and immunophenotype with conventional markers. Therefore, additional antibodies are needed to differentiate between these tumours., Methods: For this purpose, a panel of immunohistochemical stains including PAX2, PAX5, PAX8 (all monoclonal) and CD70 was used on whole tumour sections of 30 thymic carcinomas and 30 atypical thymomas to determine the expression pattern of these antibodies. In addition, all tumours were stained with markers that are well known to be expressed in both tumours, including pancytokeratin and cytokeratin 5/6. The percentage of positive tumour cells as well as the intensity of staining were evaluated and scored., Results: PAX5 stained close to 70% of thymic carcinomas while all atypical thymomas were negative for this marker. CD70 was expressed in 18 thymic carcinomas (60%) and in 1 case of atypical thymoma (3%). On the other hand, monoclonal PAX8 was negative in all cases while PAX2 was positive in a single thymic carcinoma. Of the established stains, pancytokeratin and cytokeratin 5/6 were equally positive in both tumours., Conclusions: Among the markers explored, only PAX5 and CD70 appear to be differentially expressed and are predominantly restricted to thymic carcinomas. Therefore, in small biopsy specimens and in resections in which the morphological features remain equivocal, application of these particular stains may facilitate separation of thymic carcinoma and atypical thymoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

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., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Myasthenia gravis (MG) is etiologically associated with thymus abnormalities, but its pathology in the thymus remains unclear. In this study, we attempt to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We find that the majority of thymomas are constituted by the cortical region. However, the small medullary region is enlarged in seropositive thymomas and contains polygenic enrichment and MG-specific germinal center structures. Neuromuscular medullary thymic epithelial cells, previously identified as MG-specific autoantigen-producing cells, are enriched in the cortico-medullary junction. The medulla is characterized by a specific chemokine pattern and immune cell composition, including migratory dendritic cells and effector regulatory T cells. Similar germinal center structures and immune microenvironments are also observed in the thymic hyperplasia medulla. This study shows that the medulla and junction areas are linked to MG pathology and provides insights into future MG research., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: This study aims to present a novel surgical approach for the resection of anterior mediastinal tumors, specifically focusing on micronodular thymoma with lymphoid stroma (MNT), a rare and distinct variant of thymoma. The single subxiphoid incision technique, although reported in limited cases, offers a minimally invasive option with potential benefits. We report the case of a 76-year-old male who underwent this innovative procedure and was diagnosed with MNT, providing insight into the management and outcomes of this rare pathology., Patient Concerns: The patient presented for the excision of an anterior mediastinal tumor, with the surgery facilitated by sternal hooks to improve visualization. The rarity of MNT and its unclear prognosis underscore the need for enhanced diagnostic accuracy and tailored treatment strategies., Diagnoses: Initially diagnosed preoperatively with a thymic cyst, the patient's final diagnosis was revised to MNT following surgery, highlighting the diagnostic challenges associated with this rare tumor., Interventions: The tumor was successfully removed using minimally invasive thoracoscopic surgery through a subxiphoid single-incision, demonstrating the feasibility and potential advantages of this approach., Outcomes: The patient had a favorable postoperative course, with a swift recovery and no complications, and remained in good health without signs of relapse at the 9-month follow-up., Lessons: This case underscores the importance of recognizing the unique pathological features of MNT and the need for a cautious diagnostic approach to differentiate it from other cystic lesions. Additionally, the successful use of single-port thoracoscopy under the xiphoid process for the removal of thymic tumors suggests its potential as an effective surgical method for these challenging cases., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Molecular profiles of thymomas and recurrent thymomas are far from being defined. Herein, we report an analysis of a comprehensive genetic profile (CGP) in a highly selected cohort of recurrent thymomas. Among a cohort of 426 thymomas, the tissue was available in 23 recurrent tumors for matching the biomolecular results obtained from primary and relapse samples. A control group composed of non-recurrent thymoma patients was selected through a propensity score match analysis. CGP was performed using the NGS Tru-SightOncology assay to evaluate TMB, MSI, and molecular alterations in 523 genes. CGP does not differ when comparing initial tumor with tumor relapse. A significantly higher frequency of cell cycle control genes alterations (100.0% vs. 57.1%, p = 0.022) is detected in patients with early recurrence (<32 months) compared to late recurrent cases. The CGPs were similar in recurrent thymomas and non-recurrent thymomas. Finally, based on NGS results, an off-label treatment or clinical trial could be potentially proposed in >50% of cases (oncogenic Tier-IIC variants). In conclusion, CGPs do not substantially differ between initial tumor vs. tumor recurrence and recurrent thymomas vs. non-recurrent thymomas. Cell cycle control gene alterations are associated with an early recurrence after thymectomy. Multiple target therapies are potentially available by performing a comprehensive CGP, suggesting that a precision medicine approach on these patients could be further explored.

A 41-year-old asymptomatic male with no significant medical history had a heterogenous cystic tumor with a diameter of 5.1 cm containing fatty density in the anterior mediastinum and a nearby homogeneous enhancing nodule with a diameter of 2.0 cm were observed on chest computed tomography( CT). A malignant teratoma with mediastinal lymph node metastasis was suspected preoperatively. The tumor was completely removed via median sternotomy, with concomitant resection of the lung, pericardium, and right phrenic nerve. Postoperative pathological examination revealed a large mature cystic teratoma, 6.0 cm in diameter, and a small nodule, 3.7 cm in diameter, diagnosed as stageⅠ, type B2 thymoma. The postoperative course was uneventful, with no recurrence 30 months later. The simultaneous occurrence of mature teratoma and stageⅠthymoma is extremely rare. When suspecting a teratoma with small satellite nodules preoperatively, consideration of concurrent small thymoma is suggested.

Metaplastic thymoma (MT), a rare subtype of thymic epithelial tumors (TETs), harbors YAP1::MAML2 fusions. Poroma, a skin tumor, also carries these fusions and exhibits a unique staining pattern for YAP1 immunohistochemistry (IHC), namely, a YAP1 N-terminus (YAP1[N])-positive but YAP1 C-terminus (YAP1[C])-negative pattern. In this context, MT was recently reported to lack YAP1(C) expression exclusively among TET subtypes. However, a lack of information about YAP1(N) expression in that study and another report that wild-type YAP1 expression was diminished in type B3 thymoma and thymic carcinoma warrants further studies for YAP1 expression in TETs. Thus, we immunohistochemically examined YAP1(N) and YAP1(C) staining patterns in our TET samples, including 14 cases of MT. In addition, 11 of the 14 MT cases were genetically analyzed with the formalin-fixed paraffin-embedded tissues if they harbored YAP1::MAML2 fusions. MT consistently exhibited YAP1(N)-positive and YAP(C)-negative staining, whereas type B3 thymoma and thymic carcinoma showed relatively heterogeneous staining patterns for YAP1(N) and YAP1(C) and were sometimes negative for both antibodies. Furthermore, a lower expression of YAP1 was found in type B3 compared to B2 thymomas. Among genetically analyzed 11 MT cases, 6 cases showed YAP1::MAML2 fusions, whereas the analysis failed in 5 very old cases due to poor RNA quality. These results indicate that IHC of both YAP1(N) and YAP1(C) is recommended to obtain staining patterns almost unique to MT. The biological significance of YAP1 in high-grade TETs warrants further investigation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thymic epithelial tumors, a malignancy originating in the thymus, are the commonest primary neoplasm of the anterior mediastinum; however, among thoracic tumors, they have a relatively low incidence rare. Thymic epithelial tumors can be broadly classified into thymic carcinoma and thymoma. As the cornerstone of thymic tumor treatment, surgery is the preferred treatment for early-stage patients, whereas, for advanced unresectable thymic tumors, the treatment is chemoradiotherapy. Targeted therapy is less effective for thymic tumors. Moreover, the use of immune checkpoint inhibitors as another effective treatment option for advanced unresectable thymic tumors, particularly thymomas, is limited owing to immune-related adverse effects. Here, we have summarized all pertinent information regarding chemotherapy, especially preoperative neoadjuvant chemotherapy, and chemotherapy in combination with other treatments, and reviewed the effectiveness of these procedures and recent advances in targeted therapy. In addition, we analyzed the efficacy and safety of immune checkpoint inhibitors in thymic epithelial tumors, to provide a holistic treatment view., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Some case reports have found that corticosteroid treatments shrunk thymoma lesions remarkably after the failure of chemotherapy or surgery. However, few studies have comprehensibly evaluated the antitumor effects of corticosteroids in patients with invasive thymomas., Methods: We reviewed the medical records of 13 consecutively enrolled patients with locally advanced or metastatic thymomas treated via corticosteroid monotherapies from January 2010 to March 2021 in our institute. A Cox's proportional hazard model and the Kaplan-Meier method were used to identify factors associated with survival., Results: The median follow-up time was 26 months (range, 13-115 months). The median initial dose of corticosteroid was 0.90 mg/kg/day prednisolone equivalent (range, 0.4-1.1 mg/kg/day). Of the 13 cases, 7 (53.8%, 95% CI: 0.25-0.81) exhibited a partial response and 5 (38.5%, 95% CI: 0.14-0.68) stable disease. The median progression-free survival was 5.7 months [95% confidence interval (CI): 1.5-9.6 months]. The median overall survival was 25.3 months (95% CI: 7.1-not attained). The median duration of corticosteroid use was 3 months (range, 1-64 months). Patients with WHO subtype B thymomas exhibited a better overall response rate to corticosteroids than did patients with other disease subtypes (75%, 95% CI: 0.19-0.99). Adverse events of Grade 3 or more were not observed., Conclusions: Corticosteroids are clinically valuable for patients with thymomas., Competing Interests: Declaration of competing interest Yasushi Goto received honoraria (lecture fees) from Chugai pharmaceutical Co. Ltd., Phizer, Daiichi-Sankyo, and received research funding from Phizer, Novartis, MSD, AbbVie, Daiichi-Sankyo, Preferred Networks, IQVIA, Chugai pharmaceutical Co Ltd.; Yuji Matsumoto received research funding from Hitachi, Ltd.; Yusuke Okuma received honoraria (lecture fees) from AstraZeneca, Eli Lilly Japan K.K, Chugai pharmaceutical Co. Ltd., Eisai Co. Ltd, and received research funding from Merk sharp and Dohm; Tatsuya Yoshida received honoraria (lecture fees) from AstraZeneca, Chugai pharmaceutical Co Ltd., and received research funding from Novartis, AbbVie, Amgen, Daiichi-Sankyo, AstraZeneca, MSD, Chugai pharmaceutical Co Ltd., Astellas Pharma Inc., Medpace, Boehringer Ingelheim, Bristol Myers Squibb, MSD, ONO pharmaceutical Co. Ltd., MERCK; Hidehito Horinouchi received honoraria (lecture fees) from AstraZeneca, Chugai pharmaceutical Co. Ltd./Roche, AbbVie, Daiichi-Sankyo, received research funding from AstraZeneca, Chugai pharmaceutical Co. Ltd./Roche, AbbVie, MSD, Janssen Pharmaceutical, Amgen, Daiichi-Sankyo; Noboru Yamamoto received honoraria (lecture fees) from Chugai pharmaceutical Co. Ltd. and received research funding from Astellas, Chugai pharmaceutical Co. Ltd., Eisai Co. Ltd., Taiho Pharmaceutical Co. Ltd., Bristol-Myers Squibb K.K., Pfizer, Novartis, Eli Lilly Japan K.K, AbbVie, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa Hakko Kirin Co. Ltd., Takeda Pharmaceutical Co. Ltd., ONO pharmaceutical Co. Ltd., Janssen Pharmaceutical, MSD, MERCK, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, TORAY, KAKEN, AstraZeneca, Cmic, InventisBio, Rakuten Medical; Yuichiro Ohe received honoraria (lecture fees) from Chugai pharmaceutical Co. Ltd., Eisai and received research funding from AstraZeneca, Janssen, IQVIA, CIMIC, Syneos, MEDPACE; Tomohiro Tanaka, Ken Masuda, and Yuki Shinno have no conflict of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. The RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC., Patients and Methods: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment-naïve advanced TC. They received ramucirumab, carboplatin and paclitaxel for six cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Centralized radiologic review was carried out., Results: From November 2018 to June 2023, 52 patients were screened and 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. The Eastern Cooperative Oncology Group performance status was 0 in 68.5% and 1 in 31.4% of patients. At the present analysis carried out some months after the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95% confidence interval (CI) 63.1% to 91.6%]. At the centralized radiological review of 33/35 assessable patients, ORR was 57.6% (95% CI 39.2% to 74.5%). After a median follow-up of 31.6 months, median PFS was 18.1 months (95% CI 10.8-52.3 months) and median OS was 43.8 months (95% CI 31.9 months-not reached). Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE ≥ grade 3., Conclusions: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The role of postoperative radiotherapy (PORT) after complete tumor resection in patients with thymoma or thymic carcinoma remains controversial. We performed a meta-analysis to identify groups that would benefit from PORT., Methods: Multiple scientific databases were systematically searched for studies comparing overall survival (OS) and/or disease-free survival (DFS) between PORT and surgery alone in patients with completely resected thymomas or thymic carcinomas until April 10, 2024. A random-effects model was used for the statistical analysis., Results: A total of 31 studies with 10543 patients were included (17 studies involving 4763 patients with thymoma, seven studies involving 1045 patients with thymic carcinoma, and seven studies involving 4735 patients with mixed histological types). Notably, PORT significantly prolonged OS (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.59-0.91) and DFS (HR = 0.62, 95% CI: 0.43-0.89). Similar results were also observed when the multivariate-adjusted HRs were used as the measure of effect (OS: HR = 0.60, 95% CI: 0.43-0.83; DFS: HR = 0.48, 95% CI: 0.29-0.79). In subgroup analyses, PORT was associated with a longer OS and DFS for thymoma (HR = 0.73, 95% CI: 0.56-0.96 and HR = 0.65, 95% CI: 0.46-0.93), thymic carcinoma (HR = 0.72, 95% CI: 0.49-1.07 and HR = 0.38, 95% CI: 0.19-0.77), and stage 3-4 disease (HR = 0.50, 95% CI: 0.34-0.74 and HR = 0.44, 95% CI: 0.27-0.70), but not for stage 2 disease (HR = 0.81, 95% CI: 0.55-1.19 and HR = 0.97, 95% CI: 0.51-1.83)., Conclusions: PORT is likely to improve OS and DFS in patients with completely resected stage 3-4 thymoma or thymic carcinoma; however, the value of PORT for stage 2 disease requires further evaluation in large-scale studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The aim of this study was to develop a medical imaging and comprehensive stacked learning-based method for predicting high- and low-risk thymoma. A total of 126 patients with thymomas and 5 patients with thymic carcinoma treated at our institution, including 65 low-risk patients and 66 high-risk patients, were retrospectively recruited. Among them, 78 patients composed the training cohort, while the remaining 53 patients formed the validation cohort. We extracted 1702 features each from the patients' arterial-, venous-, and plain-phase images. Pairwise subtraction of these features yielded 1702 arterial-venous, arterial-plain, and venous-plain difference features each. The Mann‒Whitney U test and least absolute shrinkage and selection operator (LASSO) and SelectKBest methods were employed to select the best features from the training set. Six models were built with a stacked learning algorithm. By applying stacked ensemble learning, three machine learning algorithms (XGBoost, multilayer perceptron (MLP), and random forest) were combined by XGBoost to produce the the six basic imaging models. Then, the XGBoost algorithm was applied to the six basic imaging models to construct a combined radiomic model. Finally, the radiomic model was combined with clinical information to create a nomogram that could easily be used in clinical practice to predict the thymoma risk category. The areas under the curve (AUCs) of the combined radiomic model in the training and validation cohorts were 0.999 (95% CI 0.988-1.000) and 0.967 (95% CI 0.916-1.000), respectively, while those of the nomogram were 0.999 (95% CI 0.996-1.000) and 0.983 (95% CI 0.990-1.000). This study describes the application of CT-based radiomics in thymoma patients and proposes a nomogram for predicting the risk category for this disease, which could be advantageous for clinical decision-making for affected patients., (© 2024. The Author(s).)

Thymomas and mediastinal lymphomas are the most common mediastinal neoplasms in cats. While mediastinal lymphoma occurs primarily in younger cats (approximately 2 to 4 years of age), thymomas are diagnosed almost exclusively in older cats. However, the following case shows that this is not necessarily always the case.A 3-year- and 11-month-old neutered male European Shorthair was presented with a preliminary report of exercise intolerance and restricted respiration. Both symptoms occurred primarily at high ambient temperatures. Radiographically, a mediastinal mass filled a significant part of the thoracic cavity. A computed tomographic examination and ultrasound-guided TruCut biopsy were performed. Histologic examination suggested a thymoma. A sternal thoracotomy and resection of the circumferential proliferation was conducted. Subsequent histopathologic examination confirmed the suspected diagnosis of a mediastinal thymoma. The cat recovered well postoperatively, and a clinical and radiographic follow-up examination was unremarkable after 8 months., Competing Interests: Die Autoren erklären hiermit, dass sie keine geschützten, finanziellen, beruflichen oder anderen persönlichen Interessen an einer Firma oder einem Produkt haben, welche die dargestellten Inhalte oder Meinungen beeinflussen könnten., (Thieme. All rights reserved.)

This report addresses the management strategy and effectiveness of robot-assisted thoracoscopic surgery (RATS) for treating local recurrence of thymoma, a condition often complicated by severe adhesions and limited data on re-operation following median sternotomy. We report about a 43-year-old man with thymoma recurrence 4 years after thymothymectomy via a median sternotomy. Follow-up computed tomography revealed a nodule adjacent to the left brachiocephalic vein, indicating possible thymoma recurrence. Thus, re-operation was performed using a left-sided approach via RATS with an artificial pneumothorax. The manipulation space was secured with an artificial pneumothorax, and multidirectional manipulation using RATS demonstrated good efficacy. Collectively, this case highlights the efficacy of RATS as a viable approach for managing thymoma recurrence in mediastinal locations, particularly when sternotomy is complicated by severe adhesions., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

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., (© 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.)

Introduction: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT., Methods: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement., Results: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years., Conclusion: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices., Competing Interests: Disclosure The authors have no conflict of interest to disclose concerning the current work., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Abstract: Intrathyroidal thymic carcinoma (ITC) is a very rare malignant epithelial tumor of the thyroid gland with thymic epithelial differentiation. Here, we are reporting the case of an eighty-year-old man who at presentation had extrathyroidal spread to the larynx and metastasis to regional lymph nodes. Though the tumor had a relatively low-grade morphology, there were areas of high mitotic activity with areas of necrosis. The classically described ivory-white gross appearance of the tumor, histomorphology of thick bands dividing the tumor into lobules, squamous cell differentiation, tight whorls of cells resembling Hassall's corpuscle, and areas showing dense lymphocytic infiltration, together with an immunoprofile of CD5, Ckit, Tumor protein 63 (p63), and B-cell lymphoma 2 gene (bcl2) positivity, helped in diagnosing this rare entity. Though classically ITC is said to have a good prognosis, cases with spread to adjacent organs and lymph node metastasis may not have an indolent course., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Objective: The aim of this study is to describe characteristics and survival outcome of patients who underwent surgical treatment for distant thymoma relapse according to the definition of the International Thymic Malignancy Interest Group., Methods: Data of patients affected by thymoma recurrence from four different institutions were collected and retrospectively reviewed. Patients with locoregional metastases who underwent nonsurgical therapies and with incomplete data on follow-up were excluded. According to the International Thymic Malignancy Interest Group distant recurrence definition, patients with recurrence due to hematogenic localization were included. Clinical and pathologic characteristics were described using descriptive statistics, whereas survival outcome was calculated using Kaplan-Meier curves and Cox regression analysis., Results: The analysis was conducted on 40 patients. A single localization was present in 13 patients, the relapse was intrathoracic in 28 cases (70%), and lung involvement was found in 26 cases. The liver was operated in seven cases, whereas other kinds of abdominal involvement were detected in eight cases. Adjuvant treatment was administered in 22 cases (55%).Five- and 10-year overall survival (OS) were 67% and 30%, respectively. Univariable analysis identified as significant favorable factor a low-grade histology (A, B1, B2): five-year OS at 92.3% versus 53.3% in high-grade (B3-C) (p = 0.035). Site of recurrence and number of localization did not influence the prognosis, but in patients with adjuvant therapy administration, there was a survival advantage also if not statistically significant: five-year OS 84.8% versus 54.5% in patients without adjuvant therapy (p = 0.101).Multivariable analysis confirmed as independent prognostic factor low-grade histology: hazard ratio = 0.176, 95% confidence interval 0.042-0.744, p = 0.018., Conclusions: Our study revealed a good survival outcome in patients who underwent surgery for distant thymoma recurrence, independently from the number and site of the relapse localization. Patients with A, B1, or B2 histology presented a significantly better survival than patients with B3-C., Competing Interests: Disclosure All authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

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., (© 2024. Society of Surgical Oncology.)

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., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Myasthenia gravis (MG) stands as a prototypical antibody-mediated autoimmune disease: it is dependent on T cells and characterized by the presence of autoantibodies targeting proteins located on the postsynaptic surface of skeletal muscle, known as the neuromuscular junction. Patients with MG exhibit a spectrum of weakness, ranging from limited ocular muscle involvement to life-threatening respiratory failure. Recent decades have witnessed substantial progress in understanding the underlying pathophysiology, leading to the delineation of distinct subcategories within MG, including MG linked to AChR or MuSK antibodies as well as age-based distinction, thymoma-associated, and immune checkpoint inhibitor-induced MG. This heightened understanding has paved the way for the development of more precise and targeted therapeutic interventions. Notably, the FDA has recently approved therapeutic inhibitors of complement and the IgG receptor FcRn, a testament to our improved comprehension of autoantibody effector mechanisms in MG. In this Review, we delve into the various subgroups of MG, stratified by age, autoantibody type, and histology of the thymus with neoplasms. Furthermore, we explore both current and potential emerging therapeutic strategies, shedding light on the evolving landscape of MG treatment.

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 18 F-FDG uptake on 18 F-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., (© 2024. The Author(s).)

A young woman in her early 30s presented with a right thyroid mass and progressive hoarseness due to a right vocal cord palsy. The preoperative fine-needle aspiration cytology was classified as Bethesda V and she underwent a total thyroidectomy and neck dissection. Intraoperatively, the thyroid mass was adherent to the oesophagus, trachea and encasing the right recurrent laryngeal nerve which was sacrificed. Final histopathology diagnosed a rare subtype of thyroid cancer known as intrathyroidal thymic carcinoma (ITC). She was then sent for adjuvant radiotherapy after a multidisciplinary tumour board discussion. This case report highlights the difficulty in preoperative diagnosis of ITC and the importance of immunohistochemical staining in clinching the diagnosis. In view of its rarity, there have been no published consensus on the treatment of ITC, hence we would like to share some learning points through a comprehensive literature review., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Thymoma is a rare malignancy with usual location in the antero-superior mediastinum. Ectopic cervical thymoma (ECT) is an extremely rare tumor that originates from ectopic tissue, and is caused by the aberrant migration of the embryonic thymus. Our patient was a 56-year-old man who had a nodular lesion in the neck for several years. Computed tomography and Enhanced magnetic resonance imaging were performed. He underwent surgery, and a histological examination resulted in a diagnosis of type AB thymoma., (© 2024. The Author(s).)

Purpose: The aim of this study was to evaluate the potential role of [ 18 F]FDG positron emission tomography/computed tomography (PET/CT) in the characterization of thymic epithelial tumors (TETs). Materials and Methods: A total of 73 patients who underwent preoperative [ 18 F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUV max ), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI) parameters were analyzed to investigate the prediction of histopathologic grade and advanced stage. Results: The cohort included 26 patients with low-grade thymoma (LGT), 36 patients with high-grade thymoma (HGT), and 11 patients with thymic carcinoma (TC). Ninety-one percent of TC had VTS >2, whereas 31% of LGT and 75% of HGT had VTS >2. SUV max , MTV, and TLG were statistically significantly higher in the TC group than in both thymoma and HGT. Using the cutoff value of 7.25 for SUV max , TC was differentiated from thymomas with 91% sensitivity and 74% specificity. TC had significantly lower HI values than thymomas. HI parameters showed good diagnostic ability to differentiate TC from thymoma and TC from HGT. SUV max , MTV, and TLG were significantly higher in advanced-stage disease than in early-stage disease. Conclusions: Visual and quantitative parameters can reliably predict both advanced disease and the grade of primary tumor in TETs. Therefore, as a promising metabolic imaging method, [ 18 F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice.

Background/aim: Thymic carcinoma is a rare cancer type with limited treatment options. Our previous study demonstrated that statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, can prevent thymic carcinoma. However, the mechanisms through which statins affect intracellular events in cancer cells are not well understood. The aim of the study was to determine how thymic carcinoma modulates the intracellular signals in response to statin administration., Materials and Methods: We analyzed statin-induced protein phosphorylation in Ty82 human thymic carcinoma cells, which were cultured with fluvastatin, and protein phosphorylation was examined using western blotting., Results: Treating Ty82 with fluvastatin led to ERK5 phosphorylation via protein prenylation attenuation. The antitumor effects of fluvastatin on thymic carcinoma were enhanced when combined with an ERK5 inhibitor., Conclusion: Statin therapy in combination with ERK5 inhibition may be a promising therapeutic approach for treating thymic carcinoma., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To assess the prognostic factors and patterns of failure of patients consecutively treated with surgery and postoperative radiation therapy (PORT) for thymic epithelial tumours (TET)., Patients and Methods: Data from 192 TET patients who were operated and received PORT at a single centre from 1990 to 2019 was retrospectively analysed., Results: Most patients had thymoma (77 %, B247%), were classified Masaoka-Koga stage III (35 %) or IV (32 %) and had a R0 (75 %) resection. Radiotherapy was delivered at a median dose of 50.4 Gy (range, 42-66 Gy; ≥ 60 Gy in 17 %), 63 (33 %) patients were treated by intensity-modulated radiation therapy and elective nodal radiotherapy was used for 37 %. At a median follow-up of 10.9 years, the 10-year overall survival (OS) and progression-free survival (PFS) rates were 62 % (95 % CI: 54-70 %) and 47 % (95 % CI: 39-55 %), respectively. Locoregional recurrence (LRR) occurred in 72/192 (38 %) patients, distributed as 6 local, 45 regional and 21 both local and regional. LRR were mainly located to the pleura: 66/72 (92 %) and 16/72 (22 %; 16/192 in total, 8 %) were in-field. Distant relapse (DR) were observed in 30 patients (16 %), resulting in 10-year locoregional (LRC) and distant control rates of 58 % (95 % CI: 50-66 %) and 82 % (95 % CI: 77-88 %), respectively. In the multivariate analysis, Masaoka-Koga stage (HR [hazard ratio]: 1.9; p = 0.001), thymic carcinomas/neuroendocrine tumours (TC) (HR: 1.6; p = 0.045) and ECOG PS > 1 (HR: 1.9; p = 0.02) correlated with poorer OS. Higher Masaoka-Koga stage (HR: 2.6; p < 0.001) associated with a decreased LRC but not R1 status (HR: 1.2; p = 0.5) or WHO histology classification. TC (HR: 3.4; p < 0.001) and a younger age (HR: 2.5; p = 0.02) correlated with DR., Conclusion: Approximately one-third of the TET in our study experienced a LRR, mainly to the pleura, and 8% in total were in-field. The place of radiotherapy should be better defined in higher risk thymoma patients within prospective randomized studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Thymoma is frequently correlated with various autoimmune diseases. However, unequivocal therapeutic targets for thymoma remain undefined, and the role of immune checkpoints in the development of thymoma-related autoimmune illnesses is unclear. We examined 39 thymoma samples and 44 normal control samples from the GEO database. Following batch correction, we identified 224 Differentially Expressed Genes (DEGs) using the Limma package. We employed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to enrich for functional pathways of DEGs. We utilized a Protein-Protein Interaction (PPI) network to identify hub genes and determine their correlation with immune cell infiltration using CIBERSORT. Real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical staining were implemented to verify identified hub genes in vivo. Simultaneously, we evaluated the prognostic relevance of the hub gene using clinical data. We determined COL1A1, COL1A2, and BGN to be the central hub genes in thymoma. Validation via RT-qPCR, Western blot, and immunohistochemical staining established significant statistical divergence between thymoma tissue and the normal thymus for only BGN. Expression levels of BGN showed strong negative correlation with the infiltration level of B cells and CD4+ T cells, yet a significant positive correlation with the level of neutrophil infiltration. We found high immune infiltration levels of macrophages, NK cells, and Th1 cells in the thymoma microenvironment in patients with a high expression of BGN. Co-localization of BGN and macrophages within thymoma tissue was discerned via tissue staining. Clinical data dictated that thymoma patients exhibiting elevated BGN expression underwent longer hospital stays, longer lengths in intensive care units, greater hospitalization costs, and extended ventilator usage; our study, augmented by clinical information, recognized BGN as possessive of diagnostic and prognostic significance in thymoma through in silico and molecular verification experiments. Our findings offered an important objective for thymoma-treated autoimmune disease comprehension, supplemented by the strong association with immune infiltration., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intraspinal metastasis from malignant carcinomas in other body parts is rarely reported.Intraspinal metastases are often epidural,with primary tumors mostly from the lung and prostate.The extramedullary subdural metastasis of thymic carcinoma is particularly rare and prone to misdiagnosis due to overlapping imaging features with primary intraspinal tumors.This article reports one case of intraspinal metastasis of thymic carcinoma,with the main diagnostic clues including a history of thymic carcinoma,fast growth rate,and irregular shape.

Background: Thymic carcinoma is a rare cancer with an aggressive clinical presentation and no organotypic symptoms. Despite using platinum-based chemotherapy as first-line treatment, the prognosis remains poor, necessitating a novel therapeutic strategy., Methods: The artemis trial is a Phase II, single-arm, multicenter study designed to evaluate the efficacy and safety of carboplatin, paclitaxel, lenvatinib, and pembrolizumab as first-line chemotherapy for patients with advanced or recurrent thymic carcinoma. A total of 35 patients will be enrolled in this study and will receive induction therapy every 3 weeks for up to 4 cycles, followed by pembrolizumab every 3 weeks, and daily lenvatinib as maintenance therapy for up to 31 cycles (for 2 years). Lenvatinib will be continued until disease progression or unacceptable toxicity based on the discretion of the attending physician., Conclusion: The primary endpoint of the study is the objective response rate, with secondary endpoints including progression-free survival, overall survival, duration of response, disease control rate, and safety profile., Trial Registration: ClinicalTrials.gov NCT05832827 Registered on April 27, 2023, https://classic., Clinicaltrials: gov/ct2/show/NCT05832827. Japan Registry of Clinical Trials (jRCT), jRCT2031230114. Registered on May 22, 2023, https://jrct.niph.go.jp/latest-detail/jRCT2031230114., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Backgroud: The standard resection for early-stage thymoma is total thymectomy and complete tumour excision with or without myasthenia gravis but the optimal surgery mode for patients with early-stage non-myasthenic thymoma is debatable. This study analysed the oncological outcomes for non-myasthenic patients with early-stage thymoma treated by thymectomy or limited resection in the long term., Methods: Patients who had resections of thymic neoplasms at Taipei Veteran General Hospital, Taiwan between December 1997 and March 2013 were recruited, exclusive of those combined clinical evidence of myasthenia gravis were reviewed. A total of 113 patients were retrospectively reviewed with pathologic early stage (Masaoka stage I and II) thymoma who underwent limited resection or extended thymectomy to compare their long-term oncologic and surgical outcomes., Results: The median observation time was 134.1 months [interquartile range (IQR) 90.7-176.1 months]. In our cohort, 52 patients underwent extended thymectomy and 61 patients underwent limited resection. Shorter duration of surgery (p < 0.001) and length of stay (p = 0.006) were demonstrated in limited resection group. Six patients experienced thymoma recurrence, two of which had combined myasthenia gravis development after recurrence. There was no significant difference (p = 0.851) in freedom-from-recurrence, with similar 10-year freedom-from-recurrence rates between the limited resection group (96.2 %) and the thymectomy group (93.2 %). Tumour-related survival was also not significantly different between groups (p = 0.726).result CONCLUSION: Patients with early-stage non-myasthenic thymoma who underwent limited resection without complete excision of the thymus achieved similar oncologic outcomes during the long-term follow-up and better peri-operative results compared to those who underwent thymectomy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

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., (© 2024. The Author(s).)

This study, based on a population, explored the prognostic value of postoperative radiotherapy (PORT) for Masaoka-Koga IIB stage thymomas. Patients diagnosed with thymoma from 2004 to 2017 in the Surveillance, Epidemiology, and End Results (SEER) database were included in the retrospective study. Through propensity score matching, the baseline characteristics of the patients were successfully matched to mitigate the selection bias of PORT. Survival rates and survival curves were compared between the PORT and non-PORT groups, with potential confounding factors addressed using a multivariate Cox regression model. In this study, 785 cases of IIB stage thymoma were included from the SEER database, and 303 patients were successfully matched between PORT and non-PORT groups through propensity score matching, with no significant differences in baseline characteristics. In the PORT and non-PORT groups, 10-year overall survival rates were 65.2% versus 59.6%, and cancer-specific survival rates were 87.0% vs. 84.4%, PORT did not yield statistically significant improvements in overall survival (P = .275) or cancer-specific survival (P = .336) for stage IIB thymomas. Based on the SEER database, the results of our study indicated that PORT does not confer a significant survival benefit for IIB stage thymomas., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The main objective of this report was to detail the long-term follow-up data from the REMORA study, which investigated the safety and efficacy of lenvatinib in patients with thymic carcinoma. In addition, an exploratory analysis of the association between relative dose intensity (RDI) and the efficacy of lenvatinib is presented., Materials and Methods: The single-arm, open-label, phase 2 REMORA study was conducted at eight Japanese institutions. Forty-two patients received oral lenvatinib 24 mg once daily in 4-week cycles until the occurrence of intolerable adverse events or disease progression. The REMORA long-term follow-up data were evaluated, including overall survival (OS). RDI was calculated by dividing the actual dose administered to the patient by the standard recommended dose. This trial is registered on JMACCT (JMA-IIA00285) and on UMIN-CTR (UMIN000026777)., Results: The updated median OS was 28.3 months (95 % confidence interval [CI]: 17.1-34.0 months), and the OS rate at 36 months was 35.7 % (95 % CI: 21.7 %-49.9 %). When grouped by RDI of lenvatinib, the median OS was 38.5 months (95 % CI: 31.2-not estimable) in patients with ≥ 75 % RDI and 17.3 months (95 % CI: 13.4-26.2 months) in patients with < 75 % RDI (hazard ratio 0.46 [95 % CI: 0.22-0.98]; P = 0.0406) at 8 weeks. Patients who maintained their lenvatinib dose over 8 weeks had a higher objective response rate than patients whose doses were reduced (75.0 % vs 29.4 %; P = 0.0379). No new safety concerns or treatment-related deaths were reported, and lenvatinib had a tolerable safety profile., Conclusion: This follow-up report updated OS in patients with metastatic or recurrent thymic carcinoma. A higher RDI of lenvatinib at 8 weeks could be associated with improved outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Seiji Niho reports receiving grants from Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Daiichi Sankyo Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., GlaxoSmithKline K.K., Kyowa Kirin Co., Ltd., KYORIN Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd.; consulting fees from AstraZeneca K.K., Pfizer Japan Inc., and Daiichi Sankyo Co., Ltd.; and honoraria from AstraZeneca K.K., Amgen K.K., Nippon Boehringer Ingelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., KYORIN Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Merck Biopharma Co., Ltd., MSD K.K., Nippon Kayaku Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd. Jun Sato reports receiving honoraria from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., and Eisai Co., Ltd.; and payment for expert testimony from Amgen K.K. Miyako Satouchi reports receiving grants from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Janssen Pharmaceutical K.K., Amgen K.K., Pfizer Japan Inc., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., and AbbVie G.K.; and honoraria from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., MSD K.K., Chugai Pharmaceutical Co., Ltd., Amgen K.K., Pfizer Japan Inc., Bristol-Myers Squibb K.K., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Eisai Co., Ltd., Bayer Yakuhin, Ltd., and Merck Ltd. Shoichi Itoh reports receiving honoraria from Bristol-Myers Squibb K.K., AstraZeneca K.K., Amgen K.K., Chugai Pharmaceutical Co., Ltd., and Pfizer Japan Inc. Yusuke Okuma reports receiving grants from AbbVie G.K., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K. and MSD K.K.; honoraria from AstraZeneca K.K., Eli Lilly Japan K.K., Takeda Pharmaceutical Co., Ltd., Eisai Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd.; fees for participation on the advisory board for AstraZeneca K.K.; and participating leadership or fiduciary role at Daiichi Sankyo Co., Ltd. Hidenori Mizugaki has no conflicts of interest to declare. Haruyasu Murakami reports receiving grants from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., AbbVie G.K., IQVIA Services Japan K.K., Taiho Pharmaceutical Co., Ltd., and Bayer Yakuhin, Ltd.; honoraria from Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., AstraZeneca K.K., Takeda Pharmaceutical Co., Ltd., Amgen K.K., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., MSD K.K., Pfizer Japan Inc., Novartis Pharma K.K., Eli Lilly Japan K.K., Taiho Pharmaceutical Co., Ltd., Eisai Co., Ltd., and Nippon Kayaku Co., Ltd.; and fees for participation on the advisory board for Chugai Pharmaceutical Co., Ltd., GAIA BioMedicine Inc., Daiichi Sankyo Co., Ltd., and Amgen K.K. Yasuhito Fujisaka reports receiving honoraria from Eisai Co., Ltd. Toshiyuki Kozuki reports receiving grants from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Eli Lilly Japan K.K., Taiho Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., Ono Pharmaceutical Co., Ltd., MSD K.K., Kyowa Kirin Co., Ltd., Merck Biopharma Co., Ltd., Daiichi Sankyo Co., Ltd., Amgen K.K., AbbVie G.K., Sanofi K.K., Eisai Co., Ltd., Labcorp Drug Development Japan Co., Ltd., IQVIA Services Japan K.K., Gilead Sciences, Inc., and Pfizer Japan Inc.; consulting fees from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Daiichi Sankyo Co., Ltd., Bayer Yakuhin, Ltd., and AbbVie G.K.; and honoraria from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Eli Lilly Japan K.K., Taiho Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Kyowa Kirin Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Merck Biopharma Co., Ltd., Nippon Kayaku Co., Ltd., Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Sawai Pharmaceutical Co., Ltd., and Amgen K.K. Kenichi Nakamura reports receiving honoraria from Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., and AstraZeneca K.K. Ryunosuke Machida has no conflicts of interest to declare. Yuichiro Ohe reports receiving grants from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., KYORIN Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Pfizer Japan Inc., Taiho Pharmaceutical Co., Ltd., Novartis Pharma K.K., Takeda Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Janssen Pharmaceutical K.K., and Loxo Oncology, Inc.; honoraria from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., Nippon Boehringer Ingelheim Co., Ltd., Bayer Yakuhin, Ltd., Pfizer Japan Inc., MSD K.K., Taiho Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., and Kyowa Kirin Co., Ltd.; and payments for expert testimony from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., KYORIN Pharmaceutical Co., Ltd., Celltrion Healthcare Japan K.K., Amgen K.K., Nippon Kayaku Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., and AnHeart Therapeutics Inc. Toshiyuki Tamai and Hiroki Ikezawa are employees of Eisai Co., Ltd. Noboru Yamamoto reports receiving grants from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., Pfizer Japan Inc., Novartis Pharma K.K., Eli Lilly Japan K.K., AbbVie G.K., Daiichi Sankyo Co., Ltd., Bayer Yakuhin, Ltd., Nippon Boehringer Ingelheim Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., MSD K.K., Merck Ltd., GlaxoSmithKline K.K., Sumitomo Pharma Co., Ltd., Chiome Bioscience Inc., Otsuka Pharmaceutical Co., Ltd., Carna Biosciences, Inc., Genmab K.K., Shionogi & Co., Ltd., Toray Industries, Inc., Kaken Pharmaceutical Co., Ltd., AstraZeneca K.K., CMIC Co., Ltd., InventisBio Co., Ltd., and Rakuten Medical Inc.; consulting fees from Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., CMIC Co., Ltd., Chugai Pharmaceutical Co., Ltd., Merck Ltd., and HEALIOS K.K.; and honoraria from Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., and Eisai Co., Ltd., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Thymoma is closely associated with myasthenia gravis (MG). However, due to the heterogeneity of thymoma and the intricate pathogenesis of MG, it remains unclear why some patients with thymoma develop MG and others do not. In this study, we conducted a comparative phenotype analysis of thymocytes in type B thymomas in patients with MG (MG (+) thymomas) and without MG (MG (-) thymomas) via fluorescence-activated cell sorting (FACS). Our results show that the developmental stages defined by the expression of CD3, CD4, and CD8 were largely maintained in both MG (+) and MG (-) thymomas, with CD4 + CD8 + cells constituting the majority of thymocytes in type B thymoma, and no significant difference between this cell population was observed in MG (+) and MG (-) thymomas.We discovered that CD4 + CD8 + thymocytes in MG (+) thymomas expressed low levels of αβ TCR and high levels of IL-7 receptor α (IL-7Rα), whereas in MG (-) thymomas, CD4 + CD8 + thymocytes exhibited the opposite pattern of αβ TCR and IL-7Rα expression. These results suggest that the positive and negative selection processes of CD4 + CD8 + thymocytes might differ between MG (+) thymomas and MG (-) thymomas. The expression of the Helios transcription factor is induced during negative selection and marks a group of T cells that have undergone negative selection and are likely to be deleted due to strong TCR binding with self-peptides/MHC ligands. We observed that the percentage of Helios-positive CD4SP T cells was greater in MG (-) than in MG (+) thymomas. Thus, the differentially regulated selection process of CD4 + CD8 + thymocytes, which involves TCR and IL-7/IL-7Rα signaling, is associated with the presence of MG in type B thymomas.

Thymomas are benign thymic epithelial neoplasms, rarely found outside the anterior mediastinum. Although hyperthyroid states have been associated with thymic hyperplasia, only 3 thymoma cases have been previously reported in patients with Graves disease (GD), all within the anterior mediastinum. Here, we report a case of ectopic cervical thymoma in a 22-year-old female patient previously treated for GD. The patient underwent ultrasonography, computed tomography, inconclusive fine-needle aspiration, and ultimately gross dissection for diagnostic workup and definitive treatment of an anterior neck mass, producing a 2.5 × 2.3 × 1.5-cm entity consistent with Masaoka stage I and type B2 thymoma per World Health Organization classification. The patient underwent an uncomplicated subsequent clinical course, with no adjuvant radiotherapy administered. After conducting a systematic literature review, we conclude that of the 109 cases of ectopic cervical thymoma reported, this is the first to describe a case of ectopic cervical thymoma in a patient with a past medical history of GD. For GD patients in stable euthyroid remission with the persistent or recurrent presence of an anterior neck mass, the extrathyroidal origin of the mass should always be considered, including the exceptional presence of a cervical ectopic thymoma., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The purpose of this study was to evaluate the clinicopathological characteristics of patients who underwent surgical resection for thymic neuroendocrine tumors (TNET) or thymic carcinoma., Methods: In this study, we retrospectively evaluated the clinicopathological characteristics of our surgical patients at Fukuoka University Hospital from January 1995 to December 2018., Results: There were nine cases of TNET and 16 cases of thymic carcinoma. Regarding the pathological type, the TNET group included three atypical carcinoid cases, two large cell neuroendocrine tumor cases, two small cell carcinoma cases, and two other cases. The thymic carcinoma group included 15 squamous carcinoma cases and one case of adenosquamous carcinoma. Based on the Masaoka-Koga staging system, six TNET cases and 11 thymic carcinoma cases were stage III or IV. The complete resection rate was 77% in the TNET group and 81% in the thymic carcinoma group. Additional chemotherapy and/or radiotherapy was performed in five cases of TNET and 11 cases of thymic carcinoma. The five-year survival rate and five-year disease-free survival rate were 87.5% and 75.0% in the TNET group and 58.9% and 57.1% in the thymic carcinoma group, respectively, with no significant difference between the two groups (P = 0.248 and P = 0.894, respectively). In the univariate analysis, complete resection was a statistically significant prognostic factor (P = 0.017)., Conclusion: In this study, no difference in prognosis was observed between TNET and thymic carcinomas. To understand the characteristics of these tumors, further case accumulation and multicenter clinical studies are needed. (243words)., (© 2024. The Author(s).)

This case report details a rare thymic basaloid carcinoma initially misinterpreted as a mediastinal teratoma, underscoring the diagnostic challenges posed by such tumors. A 71-year-old female presented with an asymptomatic anterior mediastinal tumor discovered incidentally during a routine health examination. Surgical intervention, followed by pathological and immunohistochemical analysis including CK-pan, p63, p40, and CD117 molecules, led to a definitive diagnosis of basaloid carcinoma of the thymus. This case highlights the critical importance of differential diagnosis in mediastinal lesions, especially those presenting with multilocular thymic cysts on chest CT. The subxiphoid video-assisted thoracoscopic surgery enabled complete tumor resection with minimal trauma and favorable postoperative outcomes. The patient opted against further radiotherapy or chemotherapy and she has survived for over eight months without recurrence. This case report contributes to the growing understanding of thymic basaloid carcinoma, a rare and potentially aggressive thymic carcinoma subtype. It emphasizes the necessity for precise surgical techniques and enhanced diagnostic acumen among cardiothoracic surgeons and oncologists., (© 2024. The Author(s).)

Abstract: Pyrexia of unknown origin can be caused due to numerous infective and noninfective causes. It poses a diagnostic dilemma to the clinicians and requires a myriad of investigations for the confirmation of diagnosis. Thymomas are rare mediastinal tumors that present as anterior mediastinal mass; however, thymomas presenting as pyrexia of unknown origin has rarely been reported in the literature. We report an interesting case of a middle-aged male who presented as pyrexia of unknown origin due to thymoma., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)