Thymic small cell carcinoma (TSCC) is an exceptionally rare and aggressive extrapulmonary neuroendocrine malignancy. We report a man in his 60s presenting with acute respiratory distress while receiving antibiotics for presumed aspiration pneumonia.Chest CT excluded pulmonary embolism but revealed anterior and paracardiac mediastinal masses. Thoracoscopic resection of the paracardiac mass unexpectedly confirmed small cell carcinoma of thymic origin. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT scan showed a hypermetabolic anterior mediastinal lesion and a suspicious right upper lobe nodule, without distant metastases. The disease was staged Masaoka-Koga IIB (cT3N1M1b). Combined chemoradiotherapy led to radiological regression after 3 months.TSCC is a high-grade, aggressive neoplasm that is frequently misdiagnosed because of its non-specific presentation. This case underlines the importance of considering rare thoracic malignancies in acute settings. It illustrates the key role of early histological diagnosis, multidisciplinary evaluation and multimodal therapy in the management of extrapulmonary small cell carcinomas (EPSCC).

Background Radiotherapy (RT) can enhance immune control of distant metastases, known as the abscopal effect (AE), but it doesn’t significantly alter the immunosuppressive tumor microenvironment (TME), resulting in low AE incidence. Combining RT with immunotherapy (especially anti-PD-1/PD-L1 agents) has increased AE occurrences, though questions remain about this approach, particularly in tumors with low immunogenicity such as thymic squamous cell carcinoma (TSCC). Case description A 73-year-old woman with advanced TSCC and multiple metastases experienced disease progression after two therapies. Following palliative conventional fractionated radiotherapy (CFRT) (40Gy) for thoracic metastases, her pleural lesions outside the radiation field significantly reduced, indicating an AE. Despite subsequent immunotherapy and antiangiogenic drugs, treatment efficacy was unsatisfactory due to severe lymphopenia, possibly contributing to disease progression. Conclusion The rise of immunotherapy challenges traditional RT. To enhance AE occurrence in practice, factors like radiation dose, irradiation site, timing with ICIs, ICI drug choice, patient health, disease stage, and tumor traits must be considered. This case demonstrates that CFRT can induce an AE in TSCC but also highlights the associated risk of severe lymphopenia that may limit its durability. Monitoring and mitigating lymphopenia are crucial in optimizing combined therapy outcomes. This case provides new clinical evidence for treating recurrent TSCC with combined therapy, though more research on its immunological mechanisms is needed.

Thymic epithelial tumours (TETs) include several World Health Organization (WHO) defined histological subtypes, ranging from indolent thymomas to highly aggressive thymic carcinoma (TC). The characteristics of the tumour microenvironment (TME), including immune and metabolic profiles, and their prognostic implications across subtypes remain poorly defined. We analyzed tissue samples from 111 patients with TET treated at Sun Yat-sen University Cancer Center (SYSUCC) and transcriptome and single nucleotide polymorphism data from 119 patients in The Cancer Genome Atlas (TCGA). Mutation tree analysis was performed to delineate genetic relationships among the six WHO subtypes. Immune cell infiltration was assessed using CIBERSORT, and amino acid, fatty acid, glucose metabolic activities were quantified with gene set variation analysis. Candidate immunometabolic biomarkers for malignant subtypes were validated by immunohistochemistry in the SYSUCC cohort. The mutation tree demonstrated clear genetic divergence among TET subtypes. TC and type B3 thymomas were the most genetically distinct, in keeping with their higher malignant potential and poorer prognosis, whereas type A and AB thymomas clustered together, consistent with their indolent behavior. TME profiling identified three clusters: type A and type AB, type B1 and type B2, and type B3 and TC. Patients with TC or type B3 thymoma exhibited increased macrophage infiltration, enhanced amino acid and fatty acid metabolism, and reduced resting dendritic cells. Immunohistochemistry confirmed overexpression of CD68, GLS2, and ARG2 in aggressive subtypes. This integrative analysis highlights evolutionary divergence and TME heterogeneity across TET subtypes and identifies immunometabolic biomarkers that may support prognostic assessment and future personalised treatment stratification in aggressive TETs.

Thymic epithelial tumors (TETs) are rare malignancies with diverse histologic subtypes and complex clinical behavior, necessitating a multidisciplinary approach to care. We conducted a retrospective analysis of 52 patients with TETs treated at a tertiary cancer center, including 41 with thymoma and 11 with thymic carcinoma. The median age was 50 years for thymoma and 56 years for thymic carcinoma. Paraneoplastic syndromes, particularly myasthenia gravis, were more frequent in thymoma (46.3%) than in thymic carcinoma (9.1%). Most patients presented with advanced-stage disease (stage IIIA or higher accounted for 75.7% of thymoma cases and 72.8% of thymic carcinoma cases). Neoadjuvant chemotherapy was administered to 26.8% of thymoma cases and 27.3% of thymic carcinoma cases. Surgical resection was performed in 90.2% of thymoma and 63.6% of thymic carcinoma patients, with complete resection (R0) achieved in 83.8% and 71.4%, respectively. Post-operative radiotherapy (RT) was widely utilized, delivered via volumetric-modulated arc therapy or tomotherapy. Four patients with stage IVA thymoma received hyperthermic intrathoracic chemotherapy after cytoreductive surgery. At a median follow-up of 6 years, the 5-year overall survival for thymoma and thymic carcinoma was 70.0% and 30.7%, respectively, while the 5-year progression-free survival for thymoma and thymic carcinoma was 85.1% and 26%, respectively. Relapse occurred in 17.1% of thymoma and 63.6% of thymic carcinoma patients. Despite the predominance of advanced-stage disease and large tumor burden at presentation, an aggressive, multimodal treatment approach—including high rates of R0 resection, advanced RT techniques (e.g., volumetric modulated arc therapy, tomotherapy), multiline systemic therapy, and selective hyperthermic intrathoracic chemotherapy—demonstrates potential to improve treatment outcomes. Recurrence is the strongest predictor of mortality in both thymoma and thymic carcinoma.

Thymic epithelial tumors (TETs), comprising various histologic types of thymomas and thymic carcinomas, originate from thymic epithelial cells (TECs). Each histologic type is typically associated with a distinct immune cell composition and clinical manifestation. A better understanding of the cellular origins and molecular pathways underlying this heterogeneity is needed to improve patient stratification and treatment. Here, we conducted an integrated genomic and transcriptomic analysis of 124 thymomas and 13 thymic carcinomas, including 20 newly sequenced cases combined with 117 cases from publicly available datasets. Single-cell transcriptomic data from murine thymic tissues across developmental stages was incorporated to further investigate potential cells of origin. This approach stratified TETs into three subgroups with different possible origins: GTF2I-mutant (GTF2I-type) thymomas, copy number-altered (CN-type) thymomas, and thymic carcinomas. GTF2I-type thymomas, carrying hotspot GTF2I mutations, displayed transcriptional profiles resembling thymic epithelial progenitors (TEPs). In contrast, CN-type thymomas, characterized by frequent copy-number alterations and IRS4 oncogene transcriptional activation, showed expression patterns similar to differentiated TECs. Thymic carcinomas, with high mutational burdens, exhibited profiles comparable to thymic tuft cells. The three subgroups also differed markedly in transcriptional programs, including lipid metabolism and immune phenotypes. Early acquisition of chromosomal copy-number alterations in CN-type thymomas further supported different evolutionary paths among subgroups. Together, these findings provide insights into the cellular origins and tumorigenic processes of TETs and underscore the value of integrative genomics for accurate cancer classification.

Thymic adenocarcinoma is a rare histological subtype of thymic carcinoma. Non-mucinous enteric-type thymic adenocarcinomas are extremely rare. A 54-year-old woman with an abnormality detected on chest radiography was admitted to our hospital. Chest computed tomography showed a 5.5-cm-diameter mass in the anterior mediastinum. Blood carcinoembryonic antigen (CEA) level was highly elevated at 127ng/ml (normal < 5), while other tumor markers, including alpha-fetoprotein, β-human chorionic gonadotropin, and interleukin-2R levels, were normal. Radiological findings suggested that the tumor was a thymic epithelium (Masaoka stage III). Surgery is performed for diagnostic and therapeutic purposes. Intraoperative findings revealed extensive pericardial invasion requiring a median sternotomy. The left brachiocephalic vein, pericardium, and lungs were resected along with the tumor to achieve complete resection. Histological findings revealed that the tumor was composed of tall, columnar adenocarcinoma forming irregular lumina with no mucin production. Immunohistochemistry showed that cytokeratin 20 was partially positive and caudal type homeobox 2 was positive in approximately 50% of the tumor cells. Based on the morphological and immunohistochemical findings, enteric-type thymic adenocarcinoma was diagnosed per the 5th edition of the World Health Organization classification. The tumor was subtyped according to the Masaoka (stage IVB) and TNM classification criteria (T3N1M0 stage IVA). Plasma CEA levels decreased to normal levels after surgery. Further genetic analysis of the tumor revealed a pathogenic TP53 stop-gain mutation (p.Arg213*), leading to the loss of p53 protein function. Postoperative adjuvant radiation therapy (54Gy in 27 fractions) was administered under the suspicion of incomplete microscopic resection. Reportedly, the patient is in complete remission four years post-surgery. We encountered a rare case of non-mucinous enteric-type thymic adenocarcinoma harboring a pathogenic TP53 mutation. Further studies are required to enunciate the features of this subtype of thymic carcinoma.

Thymic tumors are exceedingly rare, and most available treatment data come from pooled retrospective analyses. The cornerstone of management is resection, with the use of systemic therapy and radiation therapy (RT) as tools to facilitate surgery and prevent recurrence, or as primary management in unresectable or metastatic disease. Despite the challenges of managing such rare entities, a number of advances have occurred in surgical techniques, systemic therapy, and RT indications and technologies. There is a growing shift toward minimally invasive surgical techniques and the use of surgery to treat pleural metastases, the most common site of recurrence in thymic tumors. Systemic therapy options now include targeted therapies and immunotherapy. RT continues to evolve as new data clarify postoperative recurrence risks and as more targeted treatment approaches become available. Achieving optimal outcomes relies on multidisciplinary care that thoughtfully individualizes and integrates multimodality treatments.

Efficacy and safety of first-line lenvatinib in patients with advanced or recurrent thymic carcinoma in the real-world setting.

The subtle imaging features of thymic epithelial tumors (TETs), which comprise multiple pathological subtypes of thymoma and thymic carcinoma, are of great significance for the identification of high-risk patients. Finding the radiomics features related to the immunohistochemical markers of TETs may provide a non-invasive method for the construction of a prediction model. This retrospective study analyzed non-enhanced computed tomography (NECT) images of 307 patients with TETs from two institutions. The radiomic features were extracted, clustered, and used to develop the models with machine learning algorithms. In general, the radiomics of TET patients were profiled and clustered into three clusters, which showed differences in correlation between clinicopathological characteristics, including histological type, Masaoka stage, and immunohistochemical results. Moreover, the "original-shape-flatness" and "wavelet-LHL-first-order-Median" were the most strongly correlated with CD117 and TDT expression, and the combined model of the two demonstrated predictive efficacy for CD117/TDT expression and risk groups in training and validation cohorts. This study highlights that radiomics and biomarker-associated features can serve as a non-invasive predictive biomarker for TET patients.

Autophagy, a self-destructive cellular mechanism with a paradoxical nature, plays a part in both tumor suppression and induction by providing cancer cells with metabolic substrates, resulting in cell proliferation and survival. In this study, we aim to investigate the clinical significance of four autophagy pathway components (BECLIN, p62/, LC3b, ATG3) in pathogenetic mechanisms of thymic epithelial tumors (TETs) with possible prognostic importance. Immunohistochemistry was used to evaluate the cytoplasmic expression of BECLIN, p62, LC3b, and ATG3 in tumor cells of 99 TETs, and possible correlations with clinicopathological parameters were examined. Higher BECLIN and p62 expression was associated with male gender (p = 0.027 and p = 0.014, respectively). B3 thymomas and thymic carcinomas (TCs) displayed higher p62 expression (p = 0.019), while LC3b expression was marginally higher in non-B3/TC TETs (p = 0.098). A positive correlation between higher BECLIN expression and advanced Masaoka-Koga stage was also observed (p = 0.009). ATG3 was not associated with any of the investigated clinicopathological parameters (p > 0.05). There was also no significant correlation between any of the four examined molecules and overall survival or relapse. Our findings indicate autophagy activation in B3/TC and advanced Masaoka-Koga stage cases. Further studies are needed to explore the role of these autophagy related proteins as potential biomarkers and therapeutic targets in TETs.

Thymic carcinoma (TC) is a rare and aggressive malignancy with poor prognosis, and its genomic landscape remains incompletely defined. Identifying the somatic alterations that shape TC biology is essential for improving diagnostic precision, developing targeted therapies, and informing early detection strategies. We performed a retrospective genomic analysis of 141 TC tumor specimens from 134 patients using de-identified data from the American Association for Cancer Research (AACR) Project GENIE® database. Somatic mutations and copy number alterations (CNAs) were characterized, and statistical analyses were conducted to evaluate associations with patient demographics (sex, race) and tumor site (primary vs. metastatic). The cohort was predominantly male (56.7%) and White (56.7%). The most frequently altered genes were TP53 (27.7%), CYLD (17.6%), and CDKN2A (12.1%). Recurrent homozygous deletions at chromosome 9p21.3 involving CDKN2A and CDKN2B were common. Sex-stratified analysis revealed several significant male-specific alterations. Although the Pacific Islander subgroup was small (n = 2), preliminary analysis suggested enrichment of alterations in key cancer-associated genes, including TP53, BRCA1, and STAT5B, underscoring the need for diverse representation in TC genomics. Notably, MTOR mutations were significantly enriched in a subset of local recurrences and lymph node metastases (n = 3; q = 0.013), suggesting a potential role in disease progression. This large-scale genomic analysis reinforces the central involvement of TP53, cell-cycle control, and chromatin-modifying pathways in TC. The identification of sex-associated and race-associated mutational patterns, together with the enrichment of MTOR alterations in recurrent and metastatic disease, highlights biologically plausible mechanisms of progression and potential therapeutic vulnerabilities. These findings support the value of comprehensive genomic profiling in TC and emphasize the need for prospective, multi-omic studies to validate these observations and guide the development of more personalized treatment strategies.

Thymic epithelial tumors in pediatric, adolescent, and young adult patients: A national cohort analysis of clinical characteristics, treatment patterns, and survival outcomes.

The accurate differentiation of thymic masses, particularly thymic carcinoma (TC), is imperative for guiding optimal treatment selection. This study investigated potential non-invasive biomarkers for discerning thymic malignancies and evaluated their clinical applicability. Clinicopathological data from 1897 patients who underwent surgical resection for thymic masses across 2 institutions were retrospectively analysed. Associations between serum tumour markers and TC diagnosis were assessed using the area under the receiver operating characteristic curve (AUC). The clinical utility of the identified tumour markers was further evaluated. In the discovery cohort from Shanghai Pulmonary Hospital (SPH), cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) levels were significantly higher in the TC group compared to both the thymoma group and the non-thymic epithelial tumour (non-TET) group (median of 2.38 ng/mL vs 1.39 ng/mL or 1.28 ng/mL, both P < .001), with AUC value of 0.778 (95% CI: 0.735-0.822) compared to thymoma and 0.808 (95% CI: 0.766-0.849) compared to non-TET group. Validation in the cohort from Renmin Hospital of Wuhan University further demonstrated significant discrimination of CYFRA 21-1 for TC diagnosis (vs thymoma: AUC = 0.681 [95% CI: 0.518-0.843]; vs non-TET: AUC = 0.801 [95% CI: 0.622-0.980]). Furthermore, high CYFRA 21-1 levels were also correlated with a shorter median disease-free survival compared to the low CYFRA 21-1 group (10.0 years vs 14.9 years, P < .001) in patients with TET in the SPH cohort. CYFRA 21-1 emerges as a reliable diagnostic biomarker for distinguishing TC from other thymic masses. Moreover, it holds promise for prognosis evaluation and potentially for recurrence surveillance.

We present the case of a woman in her 40s who presented with progressive shortness of breath, facial flushing, tachycardia that worsened when supine and bilateral leg swelling. Initial evaluation included a chest X-ray, which revealed widened mediastinum and a transthoracic echocardiogram with evidence of cardiac tamponade. A pericardiocentesis was performed, draining 900 mL of haemorrhagic fluid. Subsequent CT imaging identified a large anterior mediastinal mass invading into the superior vena cava (SVC) and extending towards the right atrium. A needle biopsy confirmed the diagnosis of thymic carcinoma. The patient remained stable and was started on chemotherapy. This case highlights the importance of considering SVC invasion in patients presenting with cardiac tamponade and mediastinal masses, particularly when positional symptoms such as orthostatic tachycardia and facial flushing are present.

Background:Computed tomography (CT) features and clinical characteristics have been shown in recent studies to be effective predictive indicators for risk stratification of thymic epithelial tumors. High-risk thymoma and thymic carcinoma (HRT-TC) are highly aggressive and are associated with poor prognoses. The aim of this study is to evaluate the predictive value of CT features and clinical characteristics to assess postoperative progression in patients with HRT-TC.Methods:Clinical and enhanced CT data were retrospectively collected from patients who underwent HRT-TC surgery between June 1, 2012, and June 1, 2022. A univariate Cox regression analysis was conducted to identify the risk factors associated with postoperative progression. A multivariate Cox regression analysis was then used to determine the independent risk factors. Three-year and 5-year single-factor models as well as multifactorial combined models were then constructed based on the results of these analyses to assess their efficacy, accuracy, and net benefit. The best-performing model was selected to create a nomogram for a consistency assessment.Results:A total of 215 patients were included in the study. The multivariate Cox regression analysis revealed that independent prognostic factors that influenced postoperative progression were the tumor length (hazard ratio [HR] = 1.027; 95% confidence interval [CI] = 1.004-1.049, P = .018), tumor resection (HR = 4.122; 95% CI = 2.054-8.274, P < .001), and the mediastinal vascular invasion (MVI; HR = 2.779; 95% CI = 1.140-6.775, P = .025). The 3-year and 5-year combined models demonstrated superior predictive efficacy, accuracy, and net benefits. The nomogram and calibration curves showed that the predicted risk probabilities from the nomogram aligned well with actual observations.Conclusions:A nomogram based on clinical and CT features provided effective predictions of progression following HRT-TC. This prognostic tool holds significant value for clinicians to guide therapeutic decisions and personalize survival assessments.

Background: Neoadjuvant chemotherapy is generally recommended for locally advanced, potentially resectable thymic epithelial tumors. However, neoadjuvant chemoradiotherapy has been proposed as an alternative approach, potentially achieving higher complete resection rates. In this study, a retrospective analysis was conducted to compare the outcomes of neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant chemotherapy (NCT). Methods: From 2009 to 2022, a total of 98 patients who underwent surgery following either NCRT (n = 30) or NCT (n = 68) for thymic epithelial tumors were included in this study. Propensity score matching was applied, resulting in two matched groups of 30 patients each. The primary endpoint was the comparison of complete (R0) resection rates between the groups. Results: In the matched cohort, the R0 resection rate was significantly higher in the NCRT group (93.3%) compared to the NCT group (73.3%; p = 0.038). The tumor regression grade was also significantly lower in the NCRT group (p = 0.002). However, no significant difference was observed in 5-year overall survival between the groups, either in patients with thymoma (100% for NCRT vs. 90.9% for NCT; p = 0.34) or thymic carcinoma (74.3% for NCRT vs. 63.2% for NCT; p = 0.82). For patients with initial local recurrence, both the 5-year overall survival and post-recurrence survival rates were 100%. Conclusions: The neoadjuvant chemoradiotherapy group demonstrated superior local control, as evidenced by improved tumor regression grades and complete resection rates. However, the absence of corresponding improvement in overall survival warrants further investigation with a larger patient cohort and a longer follow-up period.

Robot-assisted thoracoscopy (RATS) is rapidly emerging as the preferred approach for the resection of thymic epithelial tumors (TET). Current challenges include the role of RATS in locally advanced disease and combined additional resections. This single-center study included all consecutive robot-assisted surgeries for TET performed between 2018 and 2024. We report perioperative outcomes and findings from a large center for robotic surgery center. One hundred and forty-three patients underwent RATS for the resection of histologically confirmed TET, including 130 (91%) patients with thymoma and 13 (9%) patients with thymic carcinoma. The median tumor size was 54 mm (35.5-75) and most patients presented in a localized stage of disease, with 120 patients (83.9%) in TNM stage I (TNM 8th edition). The conversion rate to open surgery was 4.2% and R0 resection was achieved in 134 (93.7%) patients. Combined extended resections that included lung, pericardium or great vessels were performed in 44 (30.8%) patients and were the only independent predictor of postoperative complications in a multivariable logistic regression model (OR 2.87; p = 0.03). Robot-assisted surgery is feasible and without unexpected safety concerns for TET. Combined extended resections, often necessary for locally advanced disease, are a significant predictor of postoperative complications.

PERM associated with thymic carcinoma with triple-autoantibody positivity: case report and literature review.

BackgroundThymic squamous cell carcinoma (TSCC), the predominant subtype of thymic carcinoma, is a rare and aggressive malignancy. Although the clinical benefits of perioperative immunochemotherapy for non-small cell lung cancer have been confirmed, its role in TSCC remains unclear. This study was performed to evaluate the efficacy and safety of perioperative immunotherapy for locally advanced TSCC.MethodsThe clinical data of 10 locally advanced TSCC patients treated with perioperative immunotherapy were retrospectively analyzed. All the patients received neoadjuvant PD-1 inhibitors plus platinum-based chemotherapy, followed by surgery and adjuvant immunotherapy. Surgical and pathological outcomes, postoperative complications, treatment-related adverse events (TRAEs), and survival outcomes were all assessed.ResultsAfter neoadjuvant immunotherapy, 60% (6/10) of patients achieved partial response and 40% (4/10) obtained stable disease, with the objective response rate of 60% and disease control rate of 100%. R0 resection was achieved in 80% (8/10) of patients, with 2 achieving complete pathological response. All the patients experienced at least one grade 1–2 TRAEs, but no grade 3–4 TRAEs occurred. The most commonly TRAEs were anorexia (70%) and alopecia (70%), followed by fatigue (60%). During the follow-up of 30 months, only 2 patients were dead, with recurrence-free survival of 17 and 19 months and overall survival of 23 months for both.ConclusionPerioperative immunotherapy exhibits a promising resectable rate in locally advanced TSCC, with a manageable safety profile, although survival benefits have yet to be established. In the future, a prospective randomized controlled trial should be performed to further clarify the role of perioperative immunotherapy for locally advanced TSCC.

Thymic carcinoma is a rare and aggressive malignancy with limited treatment options, resulting in a poor prognosis. Lenvatinib, a small-molecule inhibitor targeting multiple receptor tyrosine kinases, including fibroblast growth factor receptors (FGFRs), has been approved for thymic carcinoma that progresses following platinum-based chemotherapy. However, the identification of predictive biomarkers for its efficacy remains an unmet medical need. We herein present a case of 67-year-old man with advanced thymic carcinoma who was treated with carboplatin plus paclitaxel as first-line therapy. Lenvatinib, administered as second-line therapy, achieved a durable disease control that was maintained for over 20 months-exceeding the previously reported median progression-free survival. Comprehensive genomic profiling (CGP) using the FoundationOne® CDx assay identified an oncogenic FGFR3 S249C mutation. The case, together with supporting literature, suggests the potential role of FGFR3 mutations as therapeutic targets in thymic carcinoma. Furthermore, the presence of oncogenic mutations in lenvatinib-targeted genes may serve as predictive biomarkers for durable disease control. Given the limited availability of methods to detect oncogenic mutations, including FGFR3, in patients with thymic carcinoma, early implementation of CGP testing-even in the frontline setting-may be warranted in the future.