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Thymic carcinoma is a rare malignant disease with no standard systemic chemotherapy. The purpose of the present study was to investigate tumor‐infiltrating immune cells (TIIC) in the tumor microenvironment (TME), focusing on the impact of TIIC and program death‐ligand 1 (PD‐L1) expression on clinical outcomes in thymic cancer. Patients with thymic carcinoma resected between 1973 and 2017 were investigated. The tissue specimens were analyzed through immunohistochemical staining to elucidate the prognostic effects of TIIC, their ratios and PD‐L1 in a preliminary cohort (n = 10). The density of TIIC as well as PD‐L1 expression was evaluated in intraepithelial and tumor‐stromal areas on the representative whole section of tumors. The immune factors showing significant association with disease‐free survival (DFS) were evaluated in the total cohort (n = 42). TIIC in the preliminary population showed no significant difference between the two groups. However, CD8, CD20, CD204, FOXP3 and CD20/CD204 ratio demonstrated a tendency to act as predictive markers for recurrence. In the total cohort, significant differences were observed for CD8+, CD20+ and CD204+ cells in tumor islets, and for CD8+, CD20+ and FOXP3+ cells as well as the CD8/CD204 and CD20/CD204 ratios in the stroma, indicating their prognostic effect. The prognostic effect of the PD‐L1 expression in tumor cells could not be established, possibly because of intratumoral heterogeneity. CD8, CD20 and CD204 positive TIIC in stroma were identified as possible better prognostic biomarkers, considering the heterogeneity of other biomarkers. The present study paves the way for exploring strategies of combination immunotherapy targeting B cell immunity in thymic carcinoma. The present study revealed that CD8+, CD20+ and CD204+ tumor‐infiltrating immune cells in cancer stroma might be prognostic biomarkers, considering the heterogeneity of other biomarkers, including PD‐L1 expression on tumor cells in thymic carcinoma.

Thymic lymphoepithelial carcinoma (TLEC) is a primary thymic carcinoma that accounts for about 14% of all thymic epithelial tumors and is classified into 14 types. The histological morphology is similar to lymphoepithelioma, a type of undifferentiated nasopharyngeal carcinoma. It has been reported that squamous carcinoma accounts for approximately 80% of thymic carcinoma, followed by TLEC, which accounts for 6%. TLEC has been reported to be associated with Epstein-Barr virus (EBV), with EBV infection in TLEC tumor cells first noted by Lyvraz et al. in 1985. Tumors shown to be EBV-positive are classified as TLEC if lymphoplasmacytic infiltration is lacking. However, only about 50% of the cases are positive for EBV, which is lower compared to nasopharyngeal lymphoepithelioma. Instances of EBV infection in other types of thymic epithelial tumor have been reported at lower rates, which suggests that EBV infection may have an important influence on the carcinogenesis of TLEC, though the etiology is unknown. TLEC is a highly malignant tumor with poor prognosis, as affected patients have a median survival time of 22 months, according to 58 cases from the literature, while the 5-year survival rate is 34.4%. Presently, prognosis is not considered to be affected by the presence or absence of EBV positivity.

Background: thymic basaloid carcinoma (BTC) is an extremely rare tumor, and very little data are available on BTC’s biology, clinical behavior, drug sensitivity, and patient outcomes. Methods: We performed a retrospective observational study on patients diagnosed with BTC in 11 referral centers of TYME. All BTC diagnoses were reviewed by the referring pathologist. Results: Twenty-eight patients were identified. A total of 22/28 patients were included. Eighteen patients had TNM stage I–III disease, and all underwent surgery; three patients received preoperative chemotherapy, and 10 patients received adjuvant radiotherapy. With a median follow-up of 46 (1–133) months, median overall survival (mOS) and median relapse-free survival were not reached. At 48 months, OS was 77% (95%CI 43–92), and DFS was 63% (95%CI 30–83). The median OS of the 4 patients diagnosed with metastatic disease was 7 months. Six patients received first-line systemic treatment for metastatic disease, and all showed tumor responses. Anti-tumor activity was also observed with an anti-VEGFR TKI and a multi-TKI inhibitor combined with an anti-PD1 antibody. Next-generation sequencing performed in three tumor samples did not identify actionable alterations or microsatellite instability. Conclusions: BTC is an extremely rare tumor that usually presents as a localized disease. Patients diagnosed with stage I–III disease can achieve long-term DFS, and efforts should be made to perform radical surgical resection combined with perioperative treatment whenever appropriate. Patients with advanced disease progression have a poor prognosis despite a high response rate to systemic treatments.

Thymic carcinoma is an uncommon malignancy with unclear etiology. Although human papillomavirus (HPV) has been implicated in multiple cancers, its potential association with thymic cancer remains poorly studied in large population-based cohorts. This study aimed to investigate the role of HPV in developing thymic cancer and the risk of different HPV genotypes on thymic cancer. We examined the longitudinal relationship between HPV infection and thymic cancer in a cohort of 10,558 women aged 30 to 65 years who were enrolled in 1991 or 1992 in Taiwan. Cervical cells collected at the beginning of this study were tested for 39 types of HPV. The incidence of newly developed thymic cancer was determined through a computerized linkage with the National Cancer Registry by using the topography code 164 for thymic cancer in the International Classification of Diseases, Ninth Edition. An increased risk of thymic cancer was associated with HPV infection, with an HR (95% CI) of 2.42 (0.62 to 9.38) after adjustment for age and body mass index. The level of risk was higher for infections with HPV types classified in the International Agency for Research on Cancer group 3, with an adjusted HR (95% CI) of 11.82 (2.51 to 55.70). This population-based cohort study provides longitudinal evidence that HPV infection may be associated with an increased risk of thymic cancer. While no significant overall association was observed, subgroup analysis revealed a notable association with HPV genotypes classified as IARC group 3. Additional studies are necessary to confirm the role of HPV in thymic carcinogenesis.

Background/Objectives: Thymic epithelial tumors with pleural metastasis require a multimodal treatment approach with the use of novel modalities such as hyperthermic intrathoracic chemotherapy (HITHOC). This systematic review and case report aims to summarize the existing evidence regarding HITHOC for these tumors and presents the first case of a robotic approach to HITHOC. Methods: A search in November 2023 yielded a total of 17 articles, including 281 patients who met the eligibility criteria (i.e., underwent HITHOC for treatment of a thymic epithelial tumor). Results: Variations existed among HITHOC regimens and surgical approaches. The most common complications observed were air leaks. Overall survival ranged 92–95% at 1 year, 83–91.7% at 3 years, 66.7–92% at 5 years, 40–83.3% at 10 years, and 27.8–58.2% at 15 years. Conclusions: While HITHOC for thymic epithelial tumors with pleural dissemination has been shown to yield successful outcomes in the literature, this procedure has historically been performed almost exclusively via an open thoracotomy. The robotic approach to HITHOC is feasible and affords several important benefits.

Background To assess the feasibility of the cine MR feature tracking technique for the evaluation of cardiovascular-induced morphological deformation in the diagnosis of thymic epithelial tumors (TETs). Methods Our study population consisted of 43 patients with pathologically proven TETs including 10 low-grade thymomas, 23 high-grade thymomas, and 10 thymic carcinomas. Cine MR images were acquired using a balanced steady-state free precession sequence with short periods of breath-hold in the axial and oblique planes in the slice with the largest lesion cross-sectional area. The tumor margin was manually delineated in the diastolic phase and was automatically tracked for all other cardiac phases. The change rates of the long-to-short diameter ratio (∆LSR) and tumor area (∆area) associated with pulsation were compared between the three pathological groups using the Kruskal–Wallis H test and the Mann–Whitney U test. A receiver-operating characteristic (ROC) curve analysis was performed to assess the ability of each parameter to differentiate thymic carcinomas from thymomas. Results ∆LSR and ∆area were significantly different among the three groups in the axial plane (p = 0.028 and 0.006, respectively) and in the oblique plane (p = 0.034 and 0.043, respectively). ∆LSR and ∆area values were significantly lower in thymic carcinomas than in thymomas in the axial plane (for both, p = 0.012) and in the oblique plane (p = 0.015 and 0.011, respectively). The area under the ROC curves for ∆LSR and ∆area for the diagnosis of thymic carcinoma ranged from 0.755 to 0.764. Conclusions Evaluation of morphological deformation using cine-MR feature tracking analysis can help diagnose histopathological subtypes of TETs and identify thymic carcinomas preoperatively.

Multilocular thymic cysts (MTC) are acquired multilocular cysts caused by inflammation. The rarity of such lesions and a lack of recognition make diagnosis and treatment difficult. Herein, we present our experience with a multilocular mediastinal cyst that resulted in the development of thymic cancer with metastasis over a period of 13 years. Computed tomography findings revealed an anterior mediastinal mass that was suspected to be an MTC in a 49‐year‐old man. The mass shrank gradually over a period of 7 years; however, growth was observed at 10 years after initial detection. At 13 years after detection, thymic carcinoma with multiple lung metastases was diagnosed. Resection was recommended during the follow‐up period, but the patient refused treatment. A multilocular wall and location are factors that indicate MTC. However, even if a definitive diagnosis is not made, resection of multilocular anterior mediastinal cysts should be considered as determining the preoperative diagnosis is difficult. Nevertheless, our case suggests that the coexistence of tumors with cysts is possible, and the potential for malignant tumor development exists. A multilocular mediastinal cyst suspected as multilocular thymic cyst shrank over a period of 7 years; however, thymic cancer with lung metastasis developed 13 years after initial detection. Resection should be considered for multilocular mediastinal cysts, due to the challenges they pose in preoperative diagnosis, the potential for coexisting tumors with cysts, and the risk of malignant tumor development.

Thymus carcinoma is one of the thymic epithelial neoplasms with high metastasis, which does not have any good treatment at present. High mobility group A2 (HMGA2) is highly expressed in a variety of malignant tumors, such as lung cancer, colon cancer and ovarian cancer and is closely related to tumor invasion and metastasis. The present study aimed to investigate the effect and mechanism of HMGA2 on epithelial-mesenchymal transition (EMT) in thymic cancer cells. IU-TAB-1, A549, HCT-116 and 293T cells were screened by testing the protein expression level of HMGA2 though western blotting and subjected to HMGA2 interference [small interfering (si)-HMGA2]. Cell proliferation was evaluated using the Cell Counting Kit-8 assay. Cell migration and invasion were detected using the Transwell assay. Cell apoptosis was examined using flow cytometry and β-catenin expression was observed by immunofluorescence. The levels of E-cadherin, vimentin, Wnt3a, Wnt5a and β-catenin proteins were determined by western blotting. Among the four cell lines tested, IU-TAB-1 cells demonstrated the highest expression of HMGA2 (P<0.05) and were hence selected for subsequent experiments. Compared with the control group (untransfected cells), si-HMGA2 resulted in significantly decreased proliferation, migration and invasion of IU-TAB-1 cells, whereas apoptosis was increased (P<0.05). The protein expression of vimentin, Wnt3a, Wnt5a and β-catenin was significantly decreased by si-HMGA2 compared with the control group (P<0.05), whereas E-cadherin expression was increased (P<0.05). After treatment with si-HMGA2 in combination with Wnt/β-catenin agonists (SKL2001) or inhibitors (XAV-939), EMT was respectively enhanced or inhibited in IU-TAB-1 cells. Overall, si-HMGA2 may attenuate EMT in thymic cancer cells and the mechanism may be related to the Wnt/β-catenin pathway.

Cancer patients may have increased risk for adverse cardiac events, but our understanding of cardiovascular risk in thymic cancer patients is not clear. We sought to characterize baseline cardiometabolic risk factors before thymic cancer diagnosis and the potential association between cancer treatment and subsequent cardiac events. This was a retrospective cohort study evaluating patients with thymic cancer from 2003 to 2020 compared to age- and sex-matched controls without cancer. Baseline cardiovascular risk factors, cancer characteristics, and incidence of cardiac events were collected from the health information exchange. Multivariable regression was used to examine the impact of cardiovascular risk factors and cancer therapies. We compared 296 patients with pathology-confirmed thymic cancer to 2,960 noncancer controls. Prior to cancer diagnosis, thymic cancer patients (TCPs) had lower prevalence of hypertension, dyslipidemia, and diabetes mellitus and similar rates of obesity, tobacco use, and pre-existing cardiovascular disease (CVD) compared to controls. After diagnosis, high-risk TCPs (>2 cardiovascular risk factors or pre-existing CVD) had higher risk for cardiac events (HR 3.73, 95% CI 2.88-4.83,  < 0.001). In the first 3 years after diagnosis, TCPs had higher incidence of cardiac events (HR 1.38, 95% CI 1.01-1.87,  = 0.042). High-risk TCPs who received radiotherapy or chemotherapy had higher risk of cardiac events (HR 4.99, 95% CI 2.30-10.81,  < 0.001; HR 6.24, 95% CI 2.84-13.72,  < 0.001). Compared to noncancer controls, TCPs experienced more cardiac events when adjusted for risk factors. Patients with multiple cardiovascular risk factors receiving radiotherapy or chemotherapy had higher incidence of cardiac events.

Mucoepidermoid carcinoma (MEC) is a subtype of epithelial neoplasms commonly found in salivary glands, but can also be seen in the thymus. Diagnosing MEC of the thymus is sometimes challenging due to its histological similarities with adenosquamous carcinoma (ASC). This case report describes a 64‐year‐old female with a history of metastatic endometrial adenocarcinoma who presented to an oncology clinic with a thymic mass as well as multiple mass lesions in the liver, bone, and abdominal wall. Initially diagnosed as thymic ASC based on histopathology, further genomic profiling revealed a CRTC1/MAML2 translocation, leading to the diagnosis of metastatic MEC of the thymus. Comprehensive genomic testing played a crucial role in distinguishing MEC from ASC. This case highlights the importance of genetic testing in cases of uncertain primary origins and in differentiating between morphologically similar tumors. We report a case of metastatic mucoepidermoid carcinoma (MEC) of the thymus that was challenging to distinguish from adenosquamous carcinoma due to histological similarities. Genomic testing revealed a CRTC1/MAML2 translocation, confirming metastatic MEC and indicating the critical role of genetic testing in its diagnosis.