Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies.

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.

Minimally invasive thoracoscopic resection of a micronodular thymoma with lymphoid stroma via a subxiphoid single-incision approach: A case report.

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.

Neuroendocrine neoplasms of the thymus.

Neuroendocrine neoplasms of the thymus (tNENs), including typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma, are rare tumors with scarce clinical and pathological data available in the literature. They share many common features with neuroendocrine neoplasms in other organs, such as those in the lungs, while demonstrating some distinct clinical and pathological features. This review aims to give an updated overview of each category of tNENs, focusing primarily on the pathologic diagnosis and differential diagnosis of these tumors.

Robotic radical thymectomy-right-sided approach for a thymoma.

The utilization of a radical robotic thymectomy, with clearance of the mediastinal tissue between the two phrenic nerves for a thymoma, is well established. The complex mediastinal anatomy, limited space and the location of the heart introduce a distinctive challenge, particularly when adopting a right-sided approach to identify and dissect along the left phrenic nerve. We present our technique for performing a robotic radical thymectomy from a right-sided approach, tailored for a localized thymoma. Our goal is to showcase the efficacy and safety of this method, offering insights that can enhance surgical outcomes.

The contribution of rural/urban residence to incidence and survival in thymoma and thymic carcinoma, a retrospective cohort study of the SEER 2000-2020 database.

OBJECTIVE: Rural-urban healthcare disparities have been demonstrated throughout the United States, particularly in acquiring oncologic care. In this study, we aim to discern the role of rural-urban health disparities in thymic cancer incidence and uncover potential survival disparities. METHODS: The Surveillance, Epidemiology, and End Results (SEER) 17-State database was queried for all cases of thymoma (ICD-O-3/3 codes: 8580-8585) and thymic carcinoma (8586) located in the thymus (primary site code C37.9) diagnosed between 2000 and 2020. Residence was established using SEER Rural-Urban Continuum Codes. Incidence trend modeling for rural versus urban patients was completed using Joinpoint Regression Software. Chi-square, Kaplan-Meier with log-rank testing, and Cox proportional hazards was completed using SPSS, with significance set to p <0.05. RESULTS: Joinpoint analysis revealed a significant growth in incidence in the urban population compared to a stagnant incidence among the rural population. Disease specific survival was higher among urban patients on univariate modeling (p = 0.010), and confirmed on multivariate analysis, whereby rural living conferred an adjusted hazard ratio of 1.263 (95 % CI 1.045-1.527; p = 0.016) in comparison to urban patients. CONCLUSIONS: These findings demonstrate differences between thymic cancer incidence and outcomes in patients living in urban versus rural environments and demonstrate an important disparity.

Immunohistochemistry for YAP1 N-terminus and C-terminus highlights metaplastic thymoma and high-grade thymic epithelial tumors by different staining patterns.

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.

[Thymoma in a young adult cat]. / Thymom bei einer jung-adulten Katze.

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.

Spindle epithelial tumor with thymus-like elements (SETTLE): a diagnostic challenge with distinct therapeutic implication; case report.

Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare malignant neoplasm of the thyroid gland which is believed to arise from intrathyroidal thymic tissue. It predominantly affects young adults and children presenting with a thyroid mass of variable duration and rarely occurs in adults. It has a high overall survival with a tendency for delayed metastasis. SETTLE is a biphasic lobulated tumor composed of spindle shaped cells along with glandular formations seen on histopathological examination. Despite its typical morphology it is commonly misdiagnosed on histopathology due to its rarity and overlapping morphology with other close mimics such as a carcinoma, synovial sarcoma and thymoma. Herein we report such a case occurring in a middle aged female presenting with a neck mass. She had an initial diagnosis of metastatic poorly differentiated squamous cell carcinoma possibly with an orophayngeal primary in view of co expression of CK, p40 and p16 on immunohistochemistry. The patient underwent surgical resection with modified neck dissection. On review at our hospital it was diagnosed as SETTLE and she remains disease free after a follow-up period of 1 year. Diligent histopathological examination espoused with a judicious panel of IHC markers in conjunction with clinicoradiological findings forms the mainstay of diagnosis. Diffuse and strong p16 immunoexpression has not been documented or evaluated in literature so far, and needs to be explored for its diagnostic utility in this rare entity.

RadioGraphics Update: The Ninth Edition TNM Staging System for Thymic Epithelial Tumors.

Editor's Note.-RadioGraphics Update articles supplement or update information found in full-length articles previously published in RadioGraphics. These updates, written by at least one author of the previous article, provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes.

Predicting the risk category of thymoma with machine learning-based computed tomography radiomics signatures and their between-imaging phase differences.

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.

Postoperative radiotherapy for completely resected thymoma and thymic carcinoma: A systematic review and meta-analysis.

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.

Thymic epithelial tumor medical treatment: A narrative review.

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.

Case report: A challenging case of severe Cushing's syndrome in the course of metastatic thymic neuroendocrine carcinoma with a synchronous adrenal tumor.

Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy.

Thymic carcinosarcoma with melanocytic differentiation in a dog.

Carcinosarcomas are very rare tumors in dogs. Although carcinosarcomas with melanocytic differentiation arising from organs other than the thymus have been described in humans, this type of tumor has not been reported in dogs in any part of the body. We observed such a tumor in the cranial mediastinum of an 11-year-old spayed female dachshund. The dog was admitted to the clinic because of coughing, sporadic regurgitation, and dyspnea. Thoracic ultrasonography and computed tomography revealed a large mediastinal mass that was surgically removed via sternotomy. The tumor was of thymic origin and demonstrated 3 distinct components: an epithelial component positive for pancytokeratin (AE1/AE3) and high molecular weight cytokeratin (CK5/CK6) with some cystic spaces; a mesenchymal component positive for vimentin; and in association with the epithelial part, a minor melanocytic component positive for Melan A. Histologic metastasis of the epithelial and melanocytic components was present within a tracheobronchial lymph node. The dog died 105 d after surgery, after an episode of acute dyspnea. Key clinical message: To the authors' knowledge, this is the first report of thymic carcinosarcoma with melanocytic differentiation.

Carcinosarcome thymique avec différenciation mélanocytaire chez un chienLes carcinosarcomes sont des tumeurs très rares chez le chien. Bien que des carcinosarcomes avec différenciation mélanocytaire provenant d'organes autres que le thymus aient été décrits chez l'homme, ce type de tumeur n'a été rapporté chez le chien dans aucune partie du corps. Nous avons observé une telle tumeur dans le médiastin cránien d'une femelle teckel stérilisée de 11 ans. Le chien a été admis à la clinique en raison de toux, de régurgitations sporadiques et de dyspnée. L'échographie thoracique et la tomodensitométrie ont révélé une masse médiastinale importante qui a été retirée chirurgicalement par sternotomie. La tumeur était d'origine thymique et présentait 3 composantes distinctes : une composante épithéliale positive pour la pancytokératine (AE1/AE3) et la cytokératine de haut poids moléculaire (CK5/CK6) avec quelques espaces kystiques; un composant mésenchymateux positif à la vimentine; et en association avec la partie épithéliale, un composant mélanocytaire mineur positif pour Melan A. Des métastases histologiques des composants épithéliaux et mélanocytaires étaient présentes dans un ganglion lymphatique trachéobronchique. Le chien est décédé 105 jours après l'intervention chirurgicale, à la suite d'un épisode de dyspnée aiguë.Message clinique clé :À la connaissance des auteurs, il s'agit du premier cas de carcinosarcome thymique avec différenciation mélanocytaire.(Traduit par Dr Serge Messier).

Efficacy of robot-assisted thoracoscopic surgery for managing thymoma recurrence following sternotomy: a case report.

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.

The remarkable antitumor efficacy of corticosteroid treatment in patients with refractory thymomas.

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.