Thymic Carcinoma Research Articles

PAX5 and CD70 are expressed in thymic carcinoma but not in atypical thymoma (WHO type B3 thymoma): an immunohistochemical analysis of 60 cases

AimsThymic carcinoma and atypical thymoma (WHO type B3 thymoma) are unusual tumours the separation of which may be challenging in small biopsies. Both tumours consist of epithelioid tumour cells that...

MA05.03 A Phase II Study of Tislelizumab Combined with Chemotherapy in Patients with Thymic Carcinoma

MA05.03 A Phase II Study of Tislelizumab Combined with Chemotherapy in Patients with Thymic Carcinoma

P2.14A.02 Assessment of Immunohistochemical Panel Utilization in Thymic Carcinoma Diagnosis: Real World Experience Insights

P2.14A.02 Assessment of Immunohistochemical Panel Utilization in Thymic Carcinoma Diagnosis: Real World Experience Insights

Liver Metastasis Masking as Neuroendocrine Carcinoma (NEC) Predates Discovery of Intra/Peri-Thyroid Thymic Carcinoma (ITTC)

Abstract Introduction/Objective Intrathyroidal thymic carcinoma (ITTC) also known as Carcinoma showing Thymus-Like differentiation (CASTLE) is a rare malignancy comprising 0.1 to 0.15% of thyroid cancers. The WHO 5th Edition emphasizes that these tumors may also occur outside the thyroid typically at the lower pole Methods/Case Report Our aim is to show that NEC is a mimic of ITTC; that CD5, c-KIT (CD 117), p40, CK5/6 expression distinguishes ITTC from NEC, and that ITTC may at times express NE markers. Briefly, a 51-year-old man presented with hoarseness left neck mass and a PET avid liver lesion in 2016. Biopsy of the neck and liver masses revealed an infiltrating poorly differentiated “NEC” with similar morphology; positive for p53, chromogranin, and synaptophysin; negative for cam5.2, thyroglobulin, TTF-1, CD20, Pax5, CD3, CD5, S-100, calcitonin, CD56, p16, p63, c-KIT (CD117), AE1/3; and 100% staining for Ki-67. The patient underwent chemotherapy, responded well, remained under surveillance, and was symptom-free in the interim. A new 2.1 x 2.0 cm nodule appeared at the left thyroid lower pole after 6 years. The tumor was positive for CD5, CD117, p40, CK5/6, with > 95% Ki67 expression. Chromogranin, synaptophysin, CD56, thyroglobulin, calponin, TTF1, and Epstein Barr virus were negative and was overall diagnostic of ITTC Results (if a Case Study enter NA) NA Conclusion This shows the diagnostic dilemma of distinguishing ITTC from NEC which may share expression of neuroendocrine (NEC) markers and that positivity for CD5, c-KIT (CD117), p40, and CK5/6 are key diagnostic features of ITTC.

8657 Thymic Neoplasia In A Pediatric Patient With LI-Fraumeni Syndrome: A Case Report

Abstract Disclosure: M.A. Souza: None. W.M. Lins: None. D. di Matteo: None. J.L. Marcayata: None. A. Kuhn: None. H. Charcar: None. F. Ledesma: None. M.Q. Almeida: None. F. Jatene: None. B.B. Mendonca: None. M.C. Fragoso: None. Introduction: Li-Fraumeni Syndrome (LFS) is a rare autosomal dominant hereditary cancer predisposition syndrome primarily caused by pathogenic variants in the TP53 tumor suppressor gene. The individuals affected are typically young, with a cancer risk of approximately 90% in lifetime. Parents choosing to test their young children face the dilemma of when to disclose their own or the child's status and when to initiate cancer screening if LFS is detected. This process presents psychosocial challenges for both parents and affected children. Both providers and patients question whether the surveillance benefits outweigh the psychological burden of knowing LFS status and screening-related concerns, creating ambivalence toward genetic testing decisions.Case Report: We describe a 6-year-old male with Li-Fraumeni syndrome carrier of the germline pathogenic variant TP53 c.818G>A (p.R273H) in heterozygous (exon 8).In the family history, there are three relatives with advanced tumor cases, with the grandmother already deceased, the mother undergoing chemotherapy treatment, and the cousin being cancer-free for 10 years.The patient in question had no gestational complications. No consanguinity between parents. No signs or symptoms of hormonal hyperfunction. As proposed in the literature, Li-Fraumeni Syndrome patients should undergo frequent screening for early tumor detection, the patient began screening according to the Toronto protocol in 2018, at the age of 1 year and 7 months, through cranial and thoracic MRI, abdominal ultrasound, and annual hormonal assays. In the thoracic MRI conducted in February 2023, an enlarged and heterogeneously signaling thymus was identified, with a nodular formation (absent in previous exams), measuring about 2.5 cm. Facing suspicion of a thymoma, thymic carcinoma, or lymphoma, a biopsy guided by tomography in March 2023 was done. Histological examination was compatible with primary thymic neoplasia. During follow-up, a significant growth of the mass to 9 cm was observed. The patient underwent surgical treatment in August 2023 with resection of the mediastinal mass, and the anatomopathological examination revealed undifferentiated thymic carcinoma, followed in conjunction with the pediatric oncology team. The dilemma is about the adjuvant radiotherapy since the possibility to acquire a new tumor radio-induced such as sarcoma. We proposed to follow with MRI imaging each 3 months and if minimal signal of recurrence he will underwent radiotherapy. Conclusion: In addition to the intrinsic rarity of Li-Fraumeni Syndrome, this case draws attention to the possibility of a thymic tumor, an extremely rare neoplasm in syndrome carriers. In the literature, only scattered case reports show this association. Furthermore, this case reinforces the importance of systematic screening for investigating possible neoplasms in this susceptible population. Presentation: 6/1/2024

8657 Thymic Neoplasia in a Pediatric Patient With LI-Fraumeni Syndrome: A Case Report

Abstract Disclosure: M.A. Souza: None. W.M. Lins: None. D. di Matteo: None. J.L. Marcayata: None. A. Kuhn: None. H. Charcar: None. F. Ledesma: None. M.Q. Almeida: None. F. Jatene: None. B.B. Mendonca: None. M.C. Fragoso: None. Introduction: Li-Fraumeni Syndrome (LFS) is a rare autosomal dominant hereditary cancer predisposition syndrome primarily caused by pathogenic variants in the TP53 tumor suppressor gene. The individuals affected are typically young, with a cancer risk of approximately 90% in lifetime. Parents choosing to test their young children face the dilemma of when to disclose their own or the child's status and when to initiate cancer screening if LFS is detected. This process presents psychosocial challenges for both parents and affected children. Both providers and patients question whether the surveillance benefits outweigh the psychological burden of knowing LFS status and screening-related concerns, creating ambivalence toward genetic testing decisions.Case Report: We describe a 6-year-old male with Li-Fraumeni syndrome carrier of the germline pathogenic variant TP53 c.818G>A (p.R273H) in heterozygous (exon 8).In the family history, there are three relatives with advanced tumor cases, with the grandmother already deceased, the mother undergoing chemotherapy treatment, and the cousin being cancer-free for 10 years.The patient in question had no gestational complications. No consanguinity between parents. No signs or symptoms of hormonal hyperfunction. As proposed in the literature, Li-Fraumeni Syndrome patients should undergo frequent screening for early tumor detection, the patient began screening according to the Toronto protocol in 2018, at the age of 1 year and 7 months, through cranial and thoracic MRI, abdominal ultrasound, and annual hormonal assays. In the thoracic MRI conducted in February 2023, an enlarged and heterogeneously signaling thymus was identified, with a nodular formation (absent in previous exams), measuring about 2.5 cm. Facing suspicion of a thymoma, thymic carcinoma, or lymphoma, a biopsy guided by tomography in March 2023 was done. Histological examination was compatible with primary thymic neoplasia. During follow-up, a significant growth of the mass to 9 cm was observed. The patient underwent surgical treatment in August 2023 with resection of the mediastinal mass, and the anatomopathological examination revealed undifferentiated thymic carcinoma, followed in conjunction with the pediatric oncology team. The dilemma is about the adjuvant radiotherapy since the possibility to acquire a new tumor radio-induced such as sarcoma. We proposed to follow with MRI imaging each 3 months and if minimal signal of recurrence he will underwent radiotherapy. Conclusion: In addition to the intrinsic rarity of Li-Fraumeni Syndrome, this case draws attention to the possibility of a thymic tumor, an extremely rare neoplasm in syndrome carriers. In the literature, only scattered case reports show this association. Furthermore, this case reinforces the importance of systematic screening for investigating possible neoplasms in this susceptible population. Presentation: 6/1/2024

S1701, A randomized phase II trial of carboplatin-paclitaxel with and without ramucirumab in patients with locally advanced, recurrent, or metastatic thymic carcinoma

BackgroundThymic carcinoma is a rare and aggressive malignancy with few treatment options. Preclinical studies suggested that targeting the angiogenic pathway may be beneficial in this disease. MethodsThis randomized phase II trial enrolled patients with unresectable, locally advanced, recurrent, or metastatic thymic carcinoma. Patients were randomized to receive carboplatin-paclitaxel with or without ramucirumab. The primary endpoint was progression-free survival (PFS) and secondary endpoints included response by RECIST, disease control, toxicity, and overall survival (OS). The primary analysis was done using a 1-sided 10% level log-rank test. Target sample size was 66 patients. ResultsBetween 2018-2022, 21 patients enrolled to ramucirumab plus carboplatin-paclitaxel (RCP, n=8) and to the control arm (CP, n=13) with 1 patient on CP not meeting eligibility criteria. Due to slow accrual, the study was terminated early by the Data Safety Monitoring Board. Of the 20 eligible patients, 8 on RCP and 9 on CP received protocol treatment. PFS was not statistically different (hazard ratio [HR] 0.51; 80% confidence interval [CI]: [0.24 – 1.09]; p=0.13). There was no grade 4 or higher treatment-related adverse events with RCP, although 50% experienced grade 3 adverse events, one patient had a grade 3 thromboembolic event. Among 9 evaluable patients for toxicity on CP, one patient (11%) encountered grade 4 neutropenia and 1 patient (11%) reported grade 3 thromboembolic events. Response rates favored the RCP arm, with an 88% [7 out of 8, 80% CI 59% - 99%] response rate compared to 40% [4 out of 10, 80% CI 19%-65%] on CP arm (p=0.04). Disease control rate was higher in the RCP arm (100% vs 70%, p=0.09). At the time of analysis, as only one death has been reported, OS remains immature. ConclusionAccrual to this population is challenging and the study was closed early due to feasibility. While PFS was not statistically better with RCP, the hazard ratio was 0.51 and the lack of significance was likely due to small sample sizes. Notably, addition of ramucirumab to CP led to higher response rates than CP alone. Future research should consider exploring larger multicenter trials and other combinations to improve outcomes. Challenges in enrollment emphasize the need for innovative strategies and larger collaborations in rare malignancies like thymic carcinoma.

P2.14B.03 A Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients with Advanced Thymoma and Thymic Carcinoma

P2.14B.03 A Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients with Advanced Thymoma and Thymic Carcinoma

EP.14B.06 A Retrospective Multicenter Study Evaluating Experience of Perioperative Treatment for Thymic Squamous Cell Carcinoma

EP.14B.06 A Retrospective Multicenter Study Evaluating Experience of Perioperative Treatment for Thymic Squamous Cell Carcinoma

EP.14B.08 Thymic Carcinoma with Treatment-Related Leukemia Showing Complete Response to Bcl-2 Inhibitors: A Case Report

EP.14B.08 Thymic Carcinoma with Treatment-Related Leukemia Showing Complete Response to Bcl-2 Inhibitors: A Case Report

OA18.03 Real-World Data on the Efficacy and Safety of Lenvatinib in Patients with Previously Treated Thymic Carcinoma

OA18.03 Real-World Data on the Efficacy and Safety of Lenvatinib in Patients with Previously Treated Thymic Carcinoma

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

BackgroundThymomas 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 presentationA 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.ConclusionsThis report describes an extremely rare case of thymoma complicated with myasthenia gravis and thymic squamous cell carcinoma.

Diabetic Ketoacidosis after Pembrolizumab Treatment in a Patient with Thymic Carcinoma and No Known Diabetes Mellitus: A Case Report

Diabetic Ketoacidosis after Pembrolizumab Treatment in a Patient with Thymic Carcinoma and No Known Diabetes Mellitus: A Case Report

TMPRSS2::ETS translocation in nonprostatic malignancies: an unexpected finding in thymic carcinoma and pulmonary adenocarcinoma.

TMPRSS2::ETS translocation in nonprostatic malignancies: an unexpected finding in thymic carcinoma and pulmonary adenocarcinoma.

Abnormal Cellular Populations Shape Thymic Epithelial Tumor Heterogeneity and Anti-Tumor by Blocking Metabolic Interactions in Organoids.

A variety of abnormal epithelial cells and immature and mature immune cells in thymic epithelial tumors (TETs) affect histopathological features, the degree of malignancy, and the response to treatment. Here, gene expression, trajectory inference, and T cell antigen receptor (TCR)-based lineage tracking are profiled in TETs at single-cell resolution. An original subpopulation of KRT14+ progenitor cells with a spindle cell phenotype is shown. An abnormal infiltration of immature T cells with a TCR hyper-rearrangement state is revealed, due to the lack of CCL21+ medullary epithelial cells. For thymic carcinoma, the novel biomarkers of MSLN, CCL20, and SLC1A5 are identified and observed an elevated expression of LAG3 and HAVCR2 in malignant tumorn-infiltrating mature T cells. These common features based on the single-cell populations may inform pathological reclassification of TETs. Meanwhile, it is found that macrophages (MACs) attract thymic tumor cells through the LGALS9-SLC1A5 axis, providing them with glutamine to elicit metabolic reprogramming. This MAC-based metabolic pattern can promote malignancy progression. Additionally, an interactive immune environment in TETs is identified that correlates with the infiltration of abnormal FOXI1+ CFTR- ionocytes. Collectively, the data broaden the knowledge of TET cellular ecosystems, providing a basis for tackling histopathological diagnosis and related treatment.

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

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. 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. 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. 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.

Narrative review of indication and management of induction therapy for thymic epithelial tumors.

Thymic epithelial tumors (TETs) are rare and originate from the thymus. Thymomas and thymic carcinomas are the most common types of TETs. Of the two, thymomas tend to have a better prognosis and are typically localized, while thymic carcinomas have a worse prognosis and are more likely to spread. The Masaoka-Koga staging system is commonly used to determine the stage of TETs. Complete resection is the preferred treatment option, but treating locally advanced TETs can be challenging due to the invasion of surrounding structures. In such cases, induction therapy is administered to downstage the tumors and enable complete resection. We conducted this narrative review to evaluate the current progress in induction treatment for locally advanced TETs. The literature search was performed using PubMed and Web of Science in June 2023. Prospective and retrospective published trials, systemic and narrative reviews, and meta-analyses were included. Induction chemotherapy is often used as a preoperative treatment for advanced TETs. Platinum and anthracycline-based chemotherapy regimens are commonly used for treating thymoma (response rate, 37-100%), and complete resection is highly common. Treatment with cisplatin and etoposide, carboplatin and paclitaxel, docetaxel and cisplatin have also demonstrated effectiveness, particularly in patients with thymic carcinoma or thymoma who cannot tolerate anthracycline regimens. The emergence of immunotherapy and targeted therapies may provide additional options for the treatment of TETs. Induction radiotherapy, as the sole treatment for TETs, is not widely practiced due to concerns about potential damage to surrounding tissues. However, combining modern radiation techniques with surgery has shown promising results in selected patients. Induction chemoradiotherapy, which combines chemotherapy and radiation, is an emerging approach for treating TETs. Despite the lack of randomized trials comparing chemotherapy with chemoradiotherapy, concurrent chemoradiation with radiation doses of 40-50 Gy is often considered the optimal induction therapy for thymic carcinoma patients or in more advanced special situations, such as great vessel invasion. Overall, the optimal treatment for locally advanced TETs remains controversial. Induction therapy, including chemotherapy, radiotherapy, or chemoradiotherapy, is administered to downstage tumors and improve resectability. The choice of treatment depends on individual factors such as tumor stage, histology, and overall patient condition. However, further research and well-designed studies are needed to determine the most effective treatment strategies for locally advanced TETs.

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.

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. 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. 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. 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.

Re-evaluation and operative indications after induction therapy for thymic epithelial tumors.

Thymic epithelial tumors (TETs), encompassing thymoma and thymic carcinoma, represent a rare and heterogeneous group of thoracic malignancies with varying prognoses and treatment strategies. Surgical resection is the cornerstone of therapy for localized stages, but the management of locally advanced or unresectable TETs often involves induction therapy, including chemotherapy and/or radiation therapy, as a neoadjuvant approach aimed at downstaging the tumor to facilitate subsequent resection. This review synthesizes current knowledge on the re-evaluation process and operative indications following induction therapy for TETs, highlighting the pivotal role of accurate assessment in guiding surgical decisions and optimizing patient outcomes. Induction therapy's efficacy is contingent upon precise re-evaluation methods to accurately gauge treatment response and assess resectability post-therapy. This review discusses the various modalities employed in re-evaluation, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT), and the significance of tumor markers, underlining their strengths and limitations. The adoption of modified RECIST criteria for TETs by the International Thymic Malignancy Interest Group (ITMIG) underscores the necessity for standardized assessment guidelines to ensure consistency and reliability across studies and clinical practices. Furthermore, we explore the implications of induction therapy on surgical decision-making, emphasizing the criteria for determining the suitability of patients for surgical intervention post-therapy. The review addresses the challenges and future perspectives associated with the re-evaluation process, including the potential for advanced imaging techniques and the integration of molecular and genetic markers to enhance the precision of treatment response assessment. In conclusion, the re-evaluation of TETs post-induction therapy is a complex but critical component of the multidisciplinary management approach for these patients. Standardizing re-evaluation methodologies and incorporating novel diagnostic tools could significantly improve the prognostication and treatment stratification, ultimately enhancing the therapeutic outcomes for patients with advanced TETs.