Hepatoid thymic carcinoma in a polycythemia vera patient treated with ropeginterferon Alfa-2b: Clinical, histopathological and molecular correlates.

Hepatoid thymic carcinoma (HTC) is an extremely rare variant of primary epithelial tumor of the thymus morphologically resembling hepatocellular carcinoma Herein, we report an additional case of HTC diagnosed in a 40-years-old man affected by polycythemia vera and treated with ropeginterferon alfa 2-b, for the first time deeply analyzing the molecular profile of this distinctive thymic malignancy. By immunohistochemistry, tumor cells were positive for cytokeratin 7-19, GLUT1, and Hep-Par-1, whereas AFP tested negative. Whole exome sequencing revealed loss of function mutations in TP53, STK11, PBRM1, SMAD3, FN1, NTRK1, and FANCD2, as well as gain of function mutations in MTOR, BCL11A and COL1A1, along with amplification of CCND3 and MDM2. This mutational landscape halfway between thymic carcinoma (TP53, PBRM1) and hepatoid variant carcinoma of other sites (STK11) suggests that, at some point during carcinogenesis, a switch occurred from an epithelial thymic phenotype to a hepatoid-like one.

An extremely rare case of thymic squamous cell carcinoma complicated with B3 thymoma and myasthenia gravis: a case report.

BACKGROUND: Thymomas complicated with myasthenia gravis are conventionally treated during thoracic surgery. Particularly, invasive thymomas are resected alongside the surrounding organs. Here, we present a case where surgical and perioperative management was performed under the presumption of thymoma with myasthenia gravis. However, definitive pathology revealed the co-occurrence of B3 thymoma and thymic squamous cell carcinoma. This case highlights the unique presentation and exceptional rarity of thymomas that are complicated by myasthenia gravis and thymic carcinoma. CASE PRESENTATION: A 65-year-old female presented with eyelid ptosis at our hospital. Following a comprehensive examination, the patient was diagnosed with myasthenia gravis. Her computed tomography (CT) scan revealed an anterior mediastinal tumor suggestive of a thymoma, prompting a referral to the Department of Thoracic Surgery. Moreover, preoperative assessment could not definitively exclude pericardial invasion. She subsequently underwent an extended thymectomy via a longitudinal sternal incision. The tumor exhibited partial invasion of the pericardium, necessitating resection and reconstruction. Definitive pathological examination confirmed the co-occurrence of B3 thymoma and thymic squamous cell carcinoma. Positive lymph node metastasis classified the patient as stage IVa according to the Union for International Cancer Control (UICC) TNM Classification of Malignant Tumors, 8th Edition, and she was started on adjuvant radiotherapy postoperatively. Currently, the patient remains under observation, with follow-up CT scans showing no signs of recurrence. CONCLUSIONS: This report describes an extremely rare case of thymoma complicated with myasthenia gravis and thymic squamous cell carcinoma.

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

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

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.

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.

Thymic Lymphoepithelial Carcinoma: A Rare Aggressive Mediastinal Mass.

Primary thymic lymphoepithelial carcinoma is a rare neoplasm of the mediastinum. The recognition of clinical, radiologic, and pathologic features can help in making an accurate diagnosis of this aggressive tumor at the earliest.Here, we present the radiologic and pathologic findings of an anterior mediastinal mass in a 44-year-old man, which turned out to be a poorly differentiated squamous cell carcinoma of thymic origin, also known as lymphoepithelioma-like thymic carcinoma.

Case report: A sustained survival benefit of third-line immunotherapy for refractory thymic carcinoma.

Thymic carcinoma (TC) is an uncommon type of thymic epithelial tumors. Patients with relapsed or refractory TCs have a poor prognosis. Immune checkpoint inhibitor monotherapy can be applied as a second-line treatment for such cases. This study reported a TC patient who did not respond to conventional chemotherapy and radiotherapy but achieved prolonged partial remission lasting 17 months following the third-line treatment with anti-programmed cell death-1 inhibitor sintilimab. This patient did not experience any serious side effects associated with sintilimab treatment. The above results demonstrated that sintilimab could be a feasible therapeutic option for refractory TC patients.

Genomic insights into molecular profiling of thymic carcinoma: a narrative review.

Background and Objective: Thymic carcinoma is an exceptionally rare cancer, with an annual incidence of just 0.15-0.29 per 100,000 people. Owing to its rarity, only few proven treatments have been developed. Understanding its genetic profile is crucial for the development of targeted therapies. However, limited studies have exclusively examined thymic carcinoma mutations, with most investigation combining thymomas and thymic carcinomas. This paper reviews findings from genetic studies focusing on thymic carcinoma alone and compares them to those of thymoma. Methods: We conducted a PubMed search for relevant English studies on thymic carcinoma genomics. Then, key papers utilizing target sequencing or whole-exome sequencing were analyzed. Key Content and Findings: The most frequently mutated genes were TP53, CDKN2A, CDKN2B, CYLD, KIT, TET2, SETD2, BAP1, and ASXL1. TP53 and CDKN2A are correlated with poor prognosis. CYLD, which regulates signaling related with proliferation and interacts with AIRE expression and T cell development, might predict the immunotherapy response. KIT mutations might enable targeted therapy. TET2, SETD2, BAP1, and ASXL1 regulate epigenetics, suggesting disruption of these mechanisms. Higher tumor mutational burden (TMB) and 16q loss distinguish thymic carcinoma from thymoma. Although some copy number aberrations are shared, thymic carcinoma exhibits a mutational profile distinct from that of thymoma. Conclusions: Thymic carcinoma demonstrates a unique genomic landscape, suggesting a molecular pathogenesis distinct from that of thymoma. Our findings revealed prognostic biomarkers such as TP53/CDKN2A and potential therapeutic targets such as KIT. Because thymic carcinoma is extremely rare, sharing molecular profiling data could provide valuable insights into the molecular mechanisms driving the development of these tumors.

Imaging of thymic epithelial tumors-a clinical practice review.

This review article comprehensively examines the diagnostic approach to thymic epithelial tumors (TETs) and other mediastinal masses, focusing on imaging modalities and differential diagnosis. Beginning with a discussion on traditional and contemporary classification systems for mediastinal tumors, including the Japanese Association for Research on the Thymus (JART) and International Thymic Interest Group (ITMIG) classifications, it highlights the shift towards computed tomography (CT)-based categorizations. Emphasis is placed on the importance of distinguishing between solid and cystic lesions in the anterior mediastinum, with detailed insights into imaging characteristics and histological features of various TET subtypes such as thymomas, thymic carcinomas, and thymic neuroendocrine tumors (NETs). The review also elucidates common differential diagnoses, including lymphomas and germ cell tumors, providing guidance on key imaging findings and considerations for accurate diagnosis. Furthermore, it underscores the significance of patient background and blood tests in differential diagnosis, discussing age-related prevalence patterns and tumor marker assessment. After addressing the diagnostic challenges posed by thymic cysts offering insights into their radiological features, management considerations, and potential complications, this review extends to other rare mediastinal lesions highlighting the need for a comprehensive evaluation for accurate identification and management of these tumors. Finally, as illustrative examples, we present six cases highlighting various aspects of anterior mediastinal tumors, including TET. These cases provide valuable insights into the diagnostic challenges, imaging characteristics, and management considerations encountered in clinical practice. The cases presented herein do not all illustrate typical images, courses, and diagnoses. However, they each contain significant implications. Thus, we present them with the belief that they will aid in understanding the intricate nuances of image diagnosis in actual clinical practice.

Postoperative radiotherapy for thymic epithelial tumors: a narrative review.

Background and Objective: Thymic epithelial tumors (TETs), including thymomas and thymic carcinomas, are rare mediastinal tumors. Surgical resection is the treatment strategy for resectable TETs, and postoperative radiotherapy (PORT) is administered to improve local control in patients with a high risk of recurrence. The rarity of TETs has led to a lack of randomized controlled trials, and the current indications for PORT rely largely on retrospective studies. This review analyzes the literature on TETs, highlighting PORT, to guide current research and future investigations. Methods: Studies that focused on TETs, addressed topics on PORT, and had English abstracts accessible online were eligible for inclusion in our review. We excluded case reports or review articles, articles written in languages other than English, articles published >30 years ago, and articles concerning thymic neuroendocrine tumors. Key Content and Findings: Masaoka or Masaoka-Koga staging, World Health Organization (WHO) histological subtype, and resection status indicate PORT in resected TETs. Current literature suggests that PORT does not improve overall survival in stage I-IIA TETs, with inconsistent results for stage IIB-III TETs. Patients with a higher risk, such as carcinomas or WHO type B, might benefit from PORT if they do not develop distant metastasis. Determining which patients will benefit most from PORT requires further investigation. For recurrent TETs, the significance of applying PORT is unclear because available data are limited. Given the long-term survival of TETs, late toxicities, including radiation pneumonitis, radiation-induced cardiotoxicities, and secondary malignancies, must be addressed. Proton beam radiotherapy might reduce toxicities by sparing organs at risk compared to conventional photon beam radiotherapy. The use of high-precision radiation therapy, along with emerging immunotherapy, targeted therapy, and minimally invasive surgery, could improve TET outcomes. Conclusions: This review consolidates the literature on PORT for TETs, factoring in the Masaoka-Koga staging, WHO histological subtypes, and resection status. Varying results regarding PORT efficacy have led to an undefined strategy for stage IIB-III TETs. Although advanced radiotherapy techniques promise to reduce radiation-induced toxicities, further research is needed to investigate the efficacy of PORT and combination therapy.

ACTN4 is associated with the malignant potential of thymic epithelial tumors through the ß-catenin/Slug pathway.

Thymic epithelial tumors (TETs) are rare tumors arising from the mediastinum. Among TETs, thymoma type B2, B3 and thymic carcinoma are highly malignant and often present invasion and dissemination. However, the biological characteristics of TETs have not been thoroughly studied, and their mechanisms of invasion and dissemination are largely unknown. α-Actinin 4 (ACTN4) is a member of actin-binding proteins and reportedly plays important roles in the progression of several cancers. In this study, we investigated the relationship between ACTN4 and characteristics of the malignant potential of TETs, such as invasion and dissemination. In vitro experiments using Ty-82 thymic carcinoma cells revealed that overexpression of ACTN4 enhanced the proliferative and invasive ability of Ty-82 cells; conversely, knockdown of ACTN4 attenuated the proliferative and invasive potential of Ty-82 cells. In western blotting (WB) experiments, ACTN4 induced the phosphorylation of extracellular signal-regulated kinase and glycogen synthase kinase 3ß to regulate the ß-catenin/Slug pathway. Furthermore, WB analysis of cancer tissue-origin spheroids from patients with TETs showed results similar to those for Ty-82 cells. In vivo experiments showed that the knockdown of ACTN4 significantly suppressed the dissemination of Ty-82 cells. A WB and immunohistochemistry staining comparison of primary and disseminated lesions of TETs using surgical specimens showed upregulated expression of ACTN4, ß-catenin, and Slug proteins in disseminated lesions. In summary, our study suggests ACTN4 is associated with malignant potential characteristics such as invasion and dissemination in TETs via the ß-catenin/Slug pathway.

[Retracted] LOXL1­AS1 promotes thymoma and thymic carcinoma progression by regulating miR­525­5p­HSPA9.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the cell invasion assay data featured in Figs. 2G and H, 5M and N, and 9K and L, and the tumor images shown in Fig. 6B, were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Oncology Reports, or were under consideration for publication at around the same time (some of which have been retracted). In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 117, 2021; DOI: 10.3892/or.2021.8068].

[Intraspinal Metastasis of Thymic Carcinoma:Report of One Case].

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.

Immunotherapy in thymic epithelial tumors: tissue predictive biomarkers for immune checkpoint inhibitors.

Thymic epithelial tumors (TETs) are rare malignant neoplasms arising in the thymus gland. Nevertheless, TETs, including thymomas (TMs), thymic carcinomas (TCs), and thymic neuroendocrine neoplasms (TNENs), are the most common mediastinal malignancies overall. A multidisciplinary approach is required for the appropriate diagnostic and therapeutic management of TETs. To date, the main therapeutic strategies are largely depended on the stage of the tumor and they include surgery with or without neoadjuvant or adjuvant therapy, represented by platinum-based chemotherapy, radiotherapy or chemoradiotherapy. Immune checkpoint inhibitors (ICIs) are ongoing under evaluation in the advanced or metastatic diseases despite the challenges related to the very low tumor mutation burden (TMB) and the high incidence of immune-related adverse events in TETs. In this regard, predictive impact of tissue biomarkers expression such as programmed cell death ligand-1 (PD-L1), and other emerging biomarkers, as well as their optimal and shared interpretation are currently under evaluation in order to predict response rates to ICIs in TETs.

Thymic Carcinoma Presenting as a Mediastinal Mass Resembling a Cardiac Tumor.

Thymoma and thymic carcinomas are a few of the rarest malignancies seen in humankind. They are mostly seen in the Asian population, many of which are reported in the Southeast Asia region like Japan, China, Vietnam, etc. They usually can be a sequela of other underlying conditions such as myasthenia gravis or some unknown mutations that express later in life.   Our patient is a young 41-year-male, a healthy and active individual who presented for evaluation of acute shortness of breath, two months after recovering from SARS-CoV-19 infection. His shortness of breath progressed while on oxygen and diuretics, a Point of Care Ultrasound (POCUS) showed cardiac tamponade and moderate pleural effusion. A Computerized Tomographic (CT) scan of the chest/abdomen/pelvis showed cardiomegaly, pleural effusion, and a mass abutting the heart. A pericardiocentesis revealed malignant cells. Thymic carcinoma was confirmed with a core biopsy and the patient was initiated on treatment rapidly to help improve symptoms and contain the growing mass.  .

Trophoblast Cell Surface Antigen 2 Expression in Thymic Carcinoma: Brief Report.

Introduction: Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein overexpressed in various cancer types. Although TROP2-targeting therapy is currently attracting attention, little is known about TROP2 expression in thymic carcinoma. Methods: TROP2 gene expression in thymic epithelial tumors was analyzed using RNA-sequencing (RNA-seq) data for 122 cases obtained from The Cancer Genome Atlas. Immunohistochemistry (IHC) staining with anti-TROP2 antibody (SP295) was performed in 26 cases of thymic carcinoma tissues surgically resected at Juntendo University. Results: RNA-seq data analysis from The Cancer Genome Atlas revealed that TACSTD2 (gene encoding TROP2) expression was significantly higher in thymic carcinoma than in thymoma (adjusted p = 6.64e-05). There was also a trend of increasing expression in the order of thymoma type B1, B2, B3, and thymic carcinoma. As for IHC in thymic carcinoma, TROP2 expression was localized to the membrane of cancer cells. Intensity 0, 1, and 2 was observed in six (23.1%), 11 (42.3%), and nine (34.6%) cases, respectively, leading to TROP2 positivity in 20 cases (76.9%). The median proportion of TROP2-positive tumor cells and the median H-score were 25.0% (range: 0%-100%) and 25.0 (range: 0-200), respectively. No relevant factors were identified in the analysis of TROP2 expression and patient background. Although not significant, high TROP2 expression (H-score ≥ 50) tended to be associated with shorter survival. Conclusions: TROP2 expression in thymic carcinoma was confirmed by both RNA-seq and IHC, with high expression observed in IHC for intensity (76.9%) and proportion. TROP2 could be a potential target in thymic carcinoma.

Rechallenge immunotherapy after immune resistance in patients with advanced thymic carcinoma.

BACKGROUNDS: Immunotherapy is effective for patients with advanced thymic carcinoma (TC). However, the effectiveness of rechallenge immunotherapy in patients who are resistant to immunotherapy has not been investigated. METHODS: Thirty-five patients with advanced TC using immunotherapy between 2016 and 2023 at Zhejiang Cancer Hospital, The Second Affiliated Hospital of Nanchang University, and Fujian Cancer Hospital were evaluated in this study. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: A total of 35 patients were included in this study. The median PFS (mPFS) for all patients was 5.43 months and the median OS (mOS) was 16 months. After rechallenge immunotherapy, only three patients achieved partial response, resulting in an overall response rate of 16.7%, and nine patients attained stable disease, resulting in a disease control rate of 66.7%. Patients who underwent rechallenge immunotherapy had shorter mPFS compared to chemotherapy (3.53 months vs. 6.00 months, P = 0.041). In addition, the incidence of Grade 3-4 treatment-related adverse events in these patients was 22.2%. CONCLUSION: Rechallenge immunotherapy has poor efficacy in immunotolerant TC patients.

Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671).

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.

Insights into molecular aspects and targeted therapy of thymic carcinoma: a narrative review.

Background and Objective: Thymic carcinomas are rare tumors derived from thymic epithelial cells. Owing to their rarity, the search for molecular biology has been conducted in combination with thymoma as one histological subtype, and only a few studies have exclusively focused on thymic carcinoma. Currently, no therapy is more effective than complete surgical resection, and the development of novel therapies, including targeted therapies, is hampered. In this review, we summarize the knowledge regarding altered genes and pathways in thymic carcinoma with recent preclinical and clinical targeted therapies. Methods: We conducted a narrative review of the relevant English literature available in PubMed and Google Scholar on genomic characteristics and targeted therapies for thymic carcinoma. Key Content and Findings: Although the literature consists of a relatively small series, it suggests that the frequently involved genes or pathways associated with thymic carcinoma are tumor suppressor genes, including TP53 and CDKN2A/B, and the receptor tyrosine kinase pathway. Targeted therapy demonstrated antitumor activity with encouraging results. However, potential predictive biomarkers have not been identified and the response to these therapies appears to be irrelevant to gene alterations. Conclusions: Some studies have revealed the molecular characteristics of thymic carcinoma, although the results of these studies have shown a different pattern of gene alterations. The further accumulation of data would be helpful in revealing the genomic landscape and establishing molecular-targeted therapies.

Update on thymic epithelial tumors: a narrative review.

Background and Objective: Thymoma, thymic carcinoma and thymic neuroendocrine tumors originate from the epithelial cells of the thymus and account for the thymic epithelial tumors (TETs). Although TETs are uncommon, they are the most frequent tumor type in the anterior mediastinum. Multidisciplinary approach is essential for their correct management. The aim of the present review is to summarize the update management for TETs. Methods: For this review, we searched in Excerpta Medica database (EMBASE) and MEDLINE until 6 September 2023. The terms used in the search included thymoma, thymic carcinoma, thymic epithelial tumors, management, immunotherapy, multiple tyrosine kinases inhibitors. Key Content and Findings: The therapeutic approach is based on histology and tumor stage and may involve surgery with or without neoadjuvant or adjuvant treatment. In the metastatic setting, platinum-based chemotherapy is the standard of care and patients who do not respond to first-line treatment have limited treatment options mainly because of the poor efficacy shown in subsequent lines of therapy. Conclusions: Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types. Immune check point inhibitors, mammalian target of rapamycin (mTOR) and antiangiogenic multikinase inhibitors have also been studied in this clinical setting.