A Rare Case of Thymic Epithelial Tumor: AB-Type Thymoma coexisting with Thymic Adenocarcinoma and Review of literature

A Rare Case of Thymic Epithelial Tumor: AB-Type Thymoma coexisting with Thymic Adenocarcinoma and Review of literature | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Rare Case of Thymic Epithelial Tumor: AB-Type Thymoma coexisting with Thymic Adenocarcinoma and Review of literature Baoxiang Pei, Zhiliang Hu, Fen Pan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7083176/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Thymic epithelial tumors are rare, with AB-type thymoma coexisting with thymic adenocarcinoma being particularly exceptional. Fewer than 50 cases of combined thymic tumors in the same anterior mediastinal mass have been reported, predominantly involving thymoma combined with squamous cell carcinoma or neuroendocrine tumors. This case report highlights an extremely rare occurrence. Case presentation : A 65-year-old female with a 40-year smoking history presented with a mediastinal mass detected on routine chest computed tomography (CT). Imaging revealed a 6.4cm×4.2cm irregular, lobulated mass in the anterior mediastinum. The patient underwent successful resection via single-port video-assisted thoracoscopic surgery. Pathological examination and immunohistochemical staining confirmed a tumor composed of AB-type thymoma and thymic adenocarcinoma. The thymoma component showed lymphocytes positive for terminal deoxynucleotidyl transferase (TdT), CD5, and CD1a, while the epithelial cells were positive for CK5/6 and P63, with a Ki67 proliferation index of approximately 80% in hostpot areas. The adenocarcinoma component was positive for CK7, CK8/18, CK5/6, CK19, and CEA (occasionally), with a Ki67 proliferation index of approximately 30%. No tumor cells were detected in the anterior superior mediastinal lymph nodes (0/2). The patient has been followed up for 4 months postoperatively and remains disease-free. Conclusions : This case emphasizes the importance of suspecting tumor heterogeneity in mediastinal masses and establishing a definitive diagnosis through pathological and immunohistochemical analysis. As more cases are reported, our understanding of these rare tumors will improve. Thymic epithelial tumors AB-type thymoma Thymic adenocarcinoma combined thymic tumors Immunohistochemical staining Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Background Thymic epithelial tumors are a rare group of neoplasms that originate from the thymus, a lymphoepithelial organ located in the anterior mediastinum. These tumors can be categorized into thymomas and thymic carcinomas, with the latter being rarer and generally having a poorer prognosis. [ 1 , 2 ] Squamous cell carcinoma represents the predominant subtype within thymic carcinomas, constituting approximately 61.8%, whereas thymic adenocarcinoma is much rarer, comprising only 0.48% − 4.0%. [ 3 , 4 ] The coexistence of thymoma and thymic carcinoma in the same anatomic location is particularly unusual and has been rarely documented in the medical literature. [ 5 , 6 ] A comprehensive review of the literature reveals that fewer than 50 cases of combined thymic tumors have been reported [ 1 ], with the majority involving combinations of thymoma with squamous cell carcinoma [ 7 , 8 ] or neuroendocrine tumors [ 9 ]. Other combinations include thymoma with lymphoma [ 10 ], carcinoid tumors [ 11 ], and in even rarer instances, with mucoepidermoid carcinoma [ 12 ] or thymic papillary adenocarcinoma [ 13 , 14 ]. Herein, we present a unique case of an AB-type thymoma coexisting with thymic adenocarcinoma. As observed in our patient, the combination is extremely rare, with only two similar cases identified in an extensive literature search [ 14 , 15 ], underscoring the necessity for further research and documentation of such occurrences. This case not only underscores the importance of considering tumor heterogeneity in mediastinal masses but also offers valuable insights into the diagnostic and therapeutic challenges. This case report aims to contribute to the current knowledge base and stimulate further investigation into the pathogenesis, diagnosis, and management of AB-type thymoma coexisting with thymic adenocarcinoma. 2. Case Presentation 2.1 Patient History and Chief Complaint The patient, a 65-year-old female, was found to have an anterior superior mediastinal mass on routine chest chest computed tomography (CT) on January 13, 2025. And she was detected during a health check-up and has no symptoms of discomfort. She had a 40-year smoking history (20 cigarettes per day), but no other significant medical history. 2.2 Imaging Findings Chest CT: A irregular, lobulated soft tissue mass (6.4cm×4.2cm) was detected in the anterior mediastinum with multiple calcifications. Additional findings included a pulmonary cyst in the right upper lobe and a small amount of right pleural effusion. Contrast-Enhanced CT (Fig. 1 ): The mass showed heterogeneous enhancement with CT values of 26-48HU in the arterial phase and 49-90HU in the venous phase, raising suspicion of malignancy. 2.3 Surgical Intervention and Pathological Findings Surgery: After assessing and ruling out any surgical risks, the patient underwent successful resection of the mediastinal mass via single-port video-assisted thoracoscopic surgery under general anesthesia. Gross Specimen: The tumor was a grayish-white to grayish-brown mass measuring 11×10×3.5 cm, with a heterogeneous texture and areas of necrosis and calcification. On cross-section, it had a hard consistency. Two anterior superior mediastinal lymph nodes were identified, with diameters ranging from 0.2 to 1.3 cm. 2.4 Pathological Diagnosis AB-Type Thymoma ( Masaoka stage I ) coexisting with Thymic Adenocarcinoma in the same anterior mediastinal mass. Anterior superior mediastinal lymph nodes (0/2) showed no evidence of tumor. 2.4.1 Microscopic features AB-Type Thymoma: Fig. 2 A indicates that the histological type is AB thymoma. Figure 2 B shows that the type B region of the thymoma consisted mainly of lymphocytes with a few small polygonal epithelial cells with bland nuclei. Figure 2 C shows that the type A region is predominantly composed of oval tumor cells that are arranged in nests, along with a few scattered lymphocytes. Thymic Adenocarcinoma: Fig. 2 D shows that the irregular glandular duct-like structures are lined with atypical epithelial cells, which have large, deeply stained nuclei, prominent nucleoli, and active mitotic figures. 2.4.2 Immunohistochemistry AB-Type Thymoma (Fig. 3 ): lymphocytes were CD1a(+), terminal deoxynucleotidyl transferase (TdT) (+), CD5(+), CD20 (focal+); epithelial cells were CK5/6(+), P63 (partially+), CK19(+), CK20(-), CD117(-). The Ki67 positivity rate in the hotspot area of thymoma is approximately 80%. Thymic Adenocarcinoma (Fig. 4 ): Tumor cells were CK5/6 (+), CK7 (+), CK8/18 (+), CK19(+), CEA (occasional+), CR(-), P40(-), TTF-1(-), with Ki67 positivity in 30% of cells. 2. 5 Postoperative follow-up The patient recovered well after surgery without significant complications. No signs of tumor recurrence or metastasis were observed within 4 months of follow-up. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. 3. Discussion Thymic adenocarcinoma represents a very uncommon type of thymic carcinoma, accounting for only 0.48% − 4.0% of all thymic epithelial tumors. [ 3 , 4 ] The etiology of thymic adenocarcinoma remains obscure, with some literature suggesting a possible association with types A or AB thymomas. [ 15 , 16 ] However, Tumors involving the coexistence of thymoma and thymic carcinoma in the same anterior mediastinal mass are exceptionally rare. The pathogenesis of such thymic tumors remains unclear. In this case, the coexistence of AB-type thymoma and thymic adenocarcinoma may be attributed to multiclonal origins or tumor microenvironment-induced heterogeneity. Some literature reviews reveal that the majority of reported thymic tumors involve combinations of thymoma with squamous cell carcinoma, neuroendocrine tumors, lymphoma or carcinoid tumors. [ 1 , 5 , 6 ] Table 1 summarizes previously reported cases involving the coexistence of thymoma and thymic carcinoma [ 7 – 9 , 12 – 15 ]. We conducted an extensive literature search and found only two similar cases of AB-type thymoma coexisting with thymic adenocarcinoma. One publication is a case report dating back 15 years, while the other constitutes a brief letter to the editor lacking a systematic review. [ 14 , 15 ] Table 1 Previously Reported Cases involving the coexistence of thymoma and thymic carcinoma Reference Thymoma Thymic carcinoma Age Treatment Outcome Jiang Y [ 7 ] Type AB Squamous Cell Carcinoma 44y Extended thymectomy Disease-free for 6 months Ohue Y [ 8 ] Type B3 Squamous Cell Carcinoma 35y Extended thymectomy Radiotherapy Chemotherapy Repeat resection for recurrent tumor Third-Line Chemotherapy Recurrence at 4 years post-op, survived 12 years since recurrence under surveillance Nagata Y [ 9 ] Type AB Large Cell Neuroendocrine Carcinoma 66y Extended thymectomy Radiotherapy No recurrence at 6 months Wu SG [ 12 ] Type B2 Mucoepidermoid Carcinoma 51y Thymectomy Chemotherapy Radiotherapy Disease-free for 12 months Zheng YW [ 13 ] Type A Thyroid Transcription Factor 1 (TTF-1) positive Adenocarcinoma 53y Thoracoscopic mediastinal tumor resection, Partial lobectomy Disease-free for 22 months after diagnosis Hosaka Y [ 14 ] Type AB Papillary Adenocarcinoma 36y Thymectomy Radiotherapy Disease-free for 11 years Kitamura M [ 15 ] Type AB Papillary Adenocarcinoma 81y Thoracoscopic mediastinal tumor resection Unknown The diagnosis of thymoma coexisting with thymic carcinoma presents significant challenges and requires a comprehensive evaluation that integrates imaging studies, pathological findings, and clinical manifestations. Imaging studies, such as CT scans, are essential for the initial detection of mediastinal masses and may provide clues to the potential malignancy of a lesion.[ 2 , 17 ] However, these imaging modalities often lack the specificity to distinguish between different tumor types. In this case, the irregular, lobulated morphology of the mass and the presence of calcifications raised suspicion of malignancy, but the exact nature of the tumor could not be determined preoperatively. Thymomas and thymic carcinomas may be asymptomatic or present with symptoms such as cough, chest pain, and dyspnea. Thymic carcinoma is usually more aggressive and more likely to metastasize to distant sites. [ 18 ] Pathological examination and immunohistochemical staining are indispensable for confirming the diagnosis. [ 19 ] In this case, the distinct immunohistochemical profiles of the two tumor components (lymphocytes positive for TdT, CD5, and CD1a, the epithelial cells positive for CK5/6 and P63 in thymoma versus CK5/6, CK7, CK8/18 and CEA positivity in adenocarcinoma) and distinct Ki67 proliferation indices (80% in thymoma hostpot areas vs. 30% in adenocarcinoma) were critical for establishing the diagnosis of AB-type thymoma coexisting with thymic adenocarcinoma. For the diagnosis of coexisting tumors, pathological examination is crucial, as imaging studies may not be able to fully differentiate between the two types of tumors. The coexistence of thymic carcinoma and thymoma presents a complex clinical scenario, necessitating careful evaluation of their interplay and appropriate management strategies. Complete surgical resection is generally considered the primary treatment modality, as it offers the best chance for cure, especially for localized tumors. [ 20 ] However, adjuvant therapies such as chemotherapy and radiation therapy may be necessary, particularly for the more aggressive components of the tumor. [ 20 ] Radiotherapy may be administered after surgery, but it requires meticulous planning and execution to prevent harm to adjacent tissues. In this case, the patient underwent complete resection of the tumor, and no signs of recurrence or metastasis were observed within four months of follow-up. However, given the potential for recurrence, long-term follow-up is essential. Thymic adenocarcinoma is associated with a poorer prognosis compared to thymoma, and patients require close monitoring for any signs of disease progression. The patient is currently under close follow-up to monitor for recurrence. The patient's long-term smoking history raises questions about the potential role of smoking in the development of thymic malignancies. Smoking is a well-known risk factor for various cancers, and it may contribute to the development of thymic tumors through chronic inflammation and the induction of genetic mutations. [ 21 , 22 ] However, the specific mechanisms linking smoking to coexisting AB-type thymoma and thymic adenocarcinoma remain to be elucidated. Further research is needed to clarify this association. Future research should focus on exploring the molecular mechanisms underlying the development of thymoma coexisting with thymic carcinoma. This includes investigating potential genetic and epigenetic alterations that may contribute to tumor heterogeneity. Additionally, the establishment of larger case series and registries will help improve our understanding of the clinical behavior and optimal management strategies for these rare tumors. 4. Conclusion Tumors with coexisting AB-type thymoma and thymic adenocarcinoma in the anterior mediastinum are challenging to diagnose preoperatively and require pathological and immunohistochemical confirmation. This case emphasizes the importance of considering tumor heterogeneity in the same anterior mediastinal masses. As more cases are reported, our understanding of these rare tumors will improve, leading to better clinical guidelines. Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Jining First People's Hospital. Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article. Consent for publication Written informed consent was obtained from the patient for the publication of this case report and accompanying images. Availability of data and materials All data generated or analysed during this study are included in this published article. Competing interests The authors declare that they have no competing interests. Funding The authors declare no financial support. Acknowledgements We would like to thank the Radiology Department and the Pathology Group and Institute of Thoracic Tumor Research for providing the pathologic investigations and CT scan images. Clinical trial number: not applicable. Author Contribution Baoxiang Pei was involved in data collection, study design, analysis, preparation, and review of manuscript. Zhiliang Hu and Fen Pan were involved in data collection and review of manuscript. All authors contributed to the article and approved the submitted version. References Marx A, Chan JKC, Chalabreysse L, Dacic S, Detterbeck F, French CA, et al. The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial, Germ Cell, and Mesenchymal Tumors? J Thorac Oncol. 2022;17(2):200–13. PDQ Adult Treatment Editorial Board. Thymoma and Thymic Carcinoma Treatment (PDQ®): Health Professional Version. 2024 Oct 25. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–. Ahmad U, Yao X, Detterbeck F, Huang J, Antonicelli A, Filosso PL, et al. Thymic carcinoma outcomes and prognosis: results of an international analysis. J Thorac Cardiovasc Surg. 2015;149(1):95–100. 101.e1-2. Shiono A, Fujino T, Kaira K, Kato T, Yasuda M, et al. Primary thymic adenocarcinoma with an aggressive clinical course: An autopsy case showing signet ring cell-like features. Thorac Cancer. 2020;11(12):3609–13. Suster S, Moran CA. Primary thymic epithelial neoplasms showing combined features of thymoma and thymic carcinoma. A clinicopathologic study of 22 cases. Am J Surg Pathol. 1996;20(12):1469–80. Weissferdt A. Combined Thymic Epithelial Neoplasms - a Review. Int J Surg Pathol. 2023;31(6):917–26. Jiang Y, Liu Y, Shi X, Mao X, Zhao Y, Fan C. An unusual combined thymic carcinoma composed of squamous cell carcinoma and type AB thymoma: a rare case report. Diagn Pathol. 2017;12(1):9. Ohue Y, Matsuoka S, Kumeda H, Agatsuma H, Hyougotani A, Toishi M, et al. Development of combined thymic carcinoma and thymoma in an extrathymic lesion during long follow-up for recurrent thymoma. Mol Clin Oncol. 2016;4(2):139–42. Nagata Y, Ohno K, Utsumi T, Sasaki Y, Suzuki Y. Large cell neuroendocrine thymic carcinoma coexisting within large WHO type AB thymoma. Jpn J Thorac Cardiovasc Surg. 2006;54(6):256–9. Almuqbil S, AlHarbi A, Alzouri FS, Elbawab HY, Alsafwani NS, Alkhunaizy Z. Primary Thymic Hodgkin Lymphoma Coexisting with Thymoma and Myasthenia Gravis: A Case Report. Am J Case Rep. 2023;24:e941792. Miller BS, Rusinko RY, Fowler L. Synchronous thymoma and thymic carcinoid in a woman with multiple endocrine neoplasia type 1: case report and review. Endocr Pract. 2008;14(6):713–6. Wu SG, Li Y, Li B, Tian XY, Li Z. Unusual combined thymic mucoepidermoid carcinoma and thymoma: a case report and review of literature. Diagn Pathol. 2014;9:8. Zheng YW, Bai LL, Jiang GY, Lin XY, Liu Y, Xu HT. Thymic adenocarcinoma accompanied by type A thymoma and pulmonary minimally invasive adenocarcinoma and harboring distinct gene alterations: A case report. Med (Baltim). 2021;100(15):e25254. Hosaka Y, Tsuchida M, Umezu H, Eimoto T, Hashimoto T, Shinohara H, et al. Primary thymic adenocarcinoma coexisting with type AB thymoma: a rare case with long-term survival. Gen Thorac Cardiovasc Surg. 2010;58(9):488–91. Kitamura M, Okada H, Miyahara S, Matsunaga A, Kadomatsu Y, Itagaki S, et al. Case of primary thymic papillary adenocarcinoma associated with type AB thymoma and thymic cysts. Pathol Int. 2020;70(6):370–2. Kalhor N, Moran CA. Primary thymic adenocarcinomas: a clinicopathological and immunohistochemical study of 16 cases with emphasis on the morphological spectrum of differentiation. Hum Pathol. 2018;74:73–82. Robinson SP, Akhondi H, Thymoma. 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025–. Tartarone A, Lerose R, Lettini AR, Tartarone M. Current Treatment Approaches for Thymic Epithelial Tumors. Life (Basel). 2023;13(5):1170. Jeong JH, Pyo JS, Kim NY, Kang DW. Diagnostic Roles of Immunohistochemistry in Thymic Tumors: Differentiation between Thymic Carcinoma and Thymoma. Diagnostics (Basel). 2020;10(7):460. Falkson CB, Vella ET, Ellis PM, Maziak DE, Ung YC, Yu E. Surgical, Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Systematic Review. J Thorac Oncol. 2023;18(3):299–312. Eriksson M, Kaerlev L, Johansen P, Afonso N, Ahrens W, Costa-Pereira A, et al. Tobacco smoking and alcohol consumption as risk factors for thymoma - A European case-control study. Cancer Epidemiol. 2019;61:133–8. Yanagiya M, Matsumoto J, Kawahara T, Yamaguchi H, Nagayama K, Anraku M, et al. Influence of Smoking and Histologic Subtype on Developing Extrathymic Malignancy in Thymoma Patients. Ann Thorac Surg. 2019;107(5):1532–9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7083176","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":494833140,"identity":"7fe8d76f-088b-42b9-b9e3-196216a51c46","order_by":0,"name":"Baoxiang Pei","email":"","orcid":"","institution":"Jining first People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Baoxiang","middleName":"","lastName":"Pei","suffix":""},{"id":494833141,"identity":"c60b3dea-ef95-40d9-9435-aacfd84c0748","order_by":1,"name":"Zhiliang Hu","email":"","orcid":"","institution":"Jining first People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhiliang","middleName":"","lastName":"Hu","suffix":""},{"id":494833142,"identity":"a23c07bf-32d0-461f-83c4-929d94385a4a","order_by":2,"name":"Fen Pan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYBACNvnzDx8k/LCRsz9w+ABxWvgkeJgNHvakGTMcPJZAnBY5CR42yQdshxMbDp8xINJh0r2HDRJ40hIb2858vPGGwU5Ot4GQFplziQ8SLGyMm3nObracw5BsbHaAkBaGBGOQLbJtEme3SfMwHEjcRoQWM4kEtsOMPfJvnhGpRSIHrEVxBsMZNiK18BxLNkgEBrIBwzFjyzkGRPhFvr354MMfwKg0YDj88MabCjs5glpQgAQPkVGDrIVUHaNgFIyCUTAiAABnEkWHu4GOeAAAAABJRU5ErkJggg==","orcid":"","institution":"Jining first People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Fen","middleName":"","lastName":"Pan","suffix":""}],"badges":[],"createdAt":"2025-07-09 11:08:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7083176/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7083176/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88310185,"identity":"4a3b62a3-226a-41f9-bc7b-d1d95fe7b2ba","added_by":"auto","created_at":"2025-08-05 06:50:15","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":100646,"visible":true,"origin":"","legend":"\u003cp\u003eThoracic enhanced computed tomography scan showed a irregular, lobulated soft tissue mass (6.4cm×4.2cm), located in the anterior mediastinum with multiple calcifications.\u003c/p\u003e","description":"","filename":"image1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7083176/v1/59f78b1a5cd4be16b4bf0f25.jpeg"},{"id":88309639,"identity":"de440c4f-c71a-4fac-8a10-d48005e25e71","added_by":"auto","created_at":"2025-08-05 06:42:16","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":128495,"visible":true,"origin":"","legend":"\u003cp\u003eMicroscopic examination of the surgical resection specimen. (A) Low magnification (40 ×) showing the overall structure of AB-Type Thymoma. (B) Higher magnification (200 ×) revealing the type B region of the thymoma, which consists mainly of lymphocytes with a few small polygonal epithelial cells with bland nuclei. (C) Type A region of the thymoma, predominantly composed of oval tumor cells arranged in nests, along with a few scattered lymphocytes. (D) Thymic adenocarcinoma characterized by irregular glandular duct-like structures lined with atypical epithelial cells, featuring large, deeply stained nuclei, prominent nucleoli, and active mitotic figures.\u003c/p\u003e","description":"","filename":"image2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7083176/v1/9c475d2ae24785efca9fa6c6.jpeg"},{"id":88309636,"identity":"db6db6c4-53f5-464b-af4a-2202f150e204","added_by":"auto","created_at":"2025-08-05 06:42:16","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":505950,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemical Staining of AB-Type Thymoma at low magnification (10 ×). (A) Terminal deoxynucleotidyl transferase (TdT) positivity and (B) CD1a positivity in lymphocytes, indicating the presence of immature T cells. (C) CD5 positivity and (D) CD20 focal positivity in lymphocytes, typical for the thymoma. (E) CD117 negative in epithelial cells. (F) High Ki67 positivity rate (approximately 80%) in hotspot areas of the thymoma, suggesting active cell proliferation. (G) CK5/6 positivity and (H) CK20 negative in epithelial cells, with partial positivity for P63 (I), indicating the epithelial nature of the tumor.\u003c/p\u003e","description":"","filename":"image3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7083176/v1/f2eb7250cdfbfd87162506fe.jpeg"},{"id":88310188,"identity":"c9ed26c3-6a6d-413c-9477-9a93821286ab","added_by":"auto","created_at":"2025-08-05 06:50:16","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":125827,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemical Staining of Thymic Adenocarcinoma at low magnification (10×). (A) CK5/6 positivity in tumor cells, consistent with adenocarcinoma. (B) Occasional CEA positivity, which can be seen in some adenocarcinomas. (C) The Ki67 staining shows approximately 30% positivity, reflecting the tumor's growth potential.\u003c/p\u003e","description":"","filename":"image4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7083176/v1/83c85b36f2bfaff3ecbaa849.jpeg"},{"id":93027574,"identity":"a37aa276-f7d1-48e5-8556-5669deb6f1e9","added_by":"auto","created_at":"2025-10-08 09:39:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1398289,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7083176/v1/3fb7931f-00bf-4d9b-983a-3e68f5a41925.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Rare Case of Thymic Epithelial Tumor: AB-Type Thymoma coexisting with Thymic Adenocarcinoma and Review of literature","fulltext":[{"header":"1. Background","content":"\u003cp\u003eThymic epithelial tumors are a rare group of neoplasms that originate from the thymus, a lymphoepithelial organ located in the anterior mediastinum. These tumors can be categorized into thymomas and thymic carcinomas, with the latter being rarer and generally having a poorer prognosis. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Squamous cell carcinoma represents the predominant subtype within thymic carcinomas, constituting approximately 61.8%, whereas thymic adenocarcinoma is much rarer, comprising only 0.48% \u0026minus;\u0026thinsp;4.0%. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] The coexistence of thymoma and thymic carcinoma in the same anatomic location is particularly unusual and has been rarely documented in the medical literature. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] A comprehensive review of the literature reveals that fewer than 50 cases of combined thymic tumors have been reported [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], with the majority involving combinations of thymoma with squamous cell carcinoma [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] or neuroendocrine tumors [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Other combinations include thymoma with lymphoma [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], carcinoid tumors [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and in even rarer instances, with mucoepidermoid carcinoma [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] or thymic papillary adenocarcinoma [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHerein, we present a unique case of an AB-type thymoma coexisting with thymic adenocarcinoma. As observed in our patient, the combination is extremely rare, with only two similar cases identified in an extensive literature search [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], underscoring the necessity for further research and documentation of such occurrences. This case not only underscores the importance of considering tumor heterogeneity in mediastinal masses but also offers valuable insights into the diagnostic and therapeutic challenges. This case report aims to contribute to the current knowledge base and stimulate further investigation into the pathogenesis, diagnosis, and management of AB-type thymoma coexisting with thymic adenocarcinoma.\u003c/p\u003e"},{"header":"2. Case Presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Patient History and Chief Complaint\u003c/h2\u003e\u003cp\u003eThe patient, a 65-year-old female, was found to have an anterior superior mediastinal mass on routine chest chest computed tomography (CT) on January 13, 2025. And she was detected during a health check-up and has no symptoms of discomfort. She had a 40-year smoking history (20 cigarettes per day), but no other significant medical history.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Imaging Findings\u003c/h2\u003e\u003cp\u003eChest CT: A irregular, lobulated soft tissue mass (6.4cm\u0026times;4.2cm) was detected in the anterior mediastinum with multiple calcifications. Additional findings included a pulmonary cyst in the right upper lobe and a small amount of right pleural effusion.\u003c/p\u003e\u003cp\u003eContrast-Enhanced CT (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e): The mass showed heterogeneous enhancement with CT values of 26-48HU in the arterial phase and 49-90HU in the venous phase, raising suspicion of malignancy.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Surgical Intervention and Pathological Findings\u003c/h2\u003e\u003cp\u003eSurgery: After assessing and ruling out any surgical risks, the patient underwent successful resection of the mediastinal mass via single-port video-assisted thoracoscopic surgery under general anesthesia.\u003c/p\u003e\u003cp\u003eGross Specimen: The tumor was a grayish-white to grayish-brown mass measuring 11\u0026times;10\u0026times;3.5 cm, with a heterogeneous texture and areas of necrosis and calcification. On cross-section, it had a hard consistency. Two anterior superior mediastinal lymph nodes were identified, with diameters ranging from 0.2 to 1.3 cm.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Pathological Diagnosis\u003c/h2\u003e\u003cp\u003eAB-Type Thymoma ( Masaoka stage I ) coexisting with Thymic Adenocarcinoma in the same anterior mediastinal mass. Anterior superior mediastinal lymph nodes (0/2) showed no evidence of tumor.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\u003ch2\u003e2.4.1 Microscopic features\u003c/h2\u003e\u003cp\u003eAB-Type Thymoma: Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA indicates that the histological type is AB thymoma. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB shows that the type B region of the thymoma consisted mainly of lymphocytes with a few small polygonal epithelial cells with bland nuclei. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC shows that the type A region is predominantly composed of oval tumor cells that are arranged in nests, along with a few scattered lymphocytes.\u003c/p\u003e\u003cp\u003eThymic Adenocarcinoma: Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD shows that the irregular glandular duct-like structures are lined with atypical epithelial cells, which have large, deeply stained nuclei, prominent nucleoli, and active mitotic figures.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\u003ch2\u003e2.4.2 Immunohistochemistry\u003c/h2\u003e\u003cp\u003eAB-Type Thymoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e): lymphocytes were CD1a(+), terminal deoxynucleotidyl transferase (TdT) (+), CD5(+), CD20 (focal+); epithelial cells were CK5/6(+), P63 (partially+), CK19(+), CK20(-), CD117(-). The Ki67 positivity rate in the hotspot area of thymoma is approximately 80%.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThymic Adenocarcinoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e): Tumor cells were CK5/6 (+), CK7 (+), CK8/18 (+), CK19(+), CEA (occasional+), CR(-), P40(-), TTF-1(-), with Ki67 positivity in 30% of cells.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\n\u003ch3\u003e2. 5 Postoperative follow-up\u003c/h3\u003e\n\u003cp\u003eThe patient recovered well after surgery without significant complications. No signs of tumor recurrence or metastasis were observed within 4 months of follow-up. Written informed consent was obtained from the patient for the publication of this case report and accompanying images.\u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eThymic adenocarcinoma represents a very uncommon type of thymic carcinoma, accounting for only 0.48% \u0026minus;\u0026thinsp;4.0% of all thymic epithelial tumors. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] The etiology of thymic adenocarcinoma remains obscure, with some literature suggesting a possible association with types A or AB thymomas. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] However, Tumors involving the coexistence of thymoma and thymic carcinoma in the same anterior mediastinal mass are exceptionally rare. The pathogenesis of such thymic tumors remains unclear. In this case, the coexistence of AB-type thymoma and thymic adenocarcinoma may be attributed to multiclonal origins or tumor microenvironment-induced heterogeneity. Some literature reviews reveal that the majority of reported thymic tumors involve combinations of thymoma with squamous cell carcinoma, neuroendocrine tumors, lymphoma or carcinoid tumors. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes previously reported cases involving the coexistence of thymoma and thymic carcinoma [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. We conducted an extensive literature search and found only two similar cases of AB-type thymoma coexisting with thymic adenocarcinoma. One publication is a case report dating back 15 years, while the other constitutes a brief letter to the editor lacking a systematic review. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePreviously Reported Cases involving the coexistence of thymoma and thymic carcinoma\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThymoma\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eThymic carcinoma\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJiang Y [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eType AB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSquamous Cell Carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e44y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eExtended thymectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDisease-free for 6 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOhue Y [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eType B3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSquamous Cell Carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eExtended thymectomy Radiotherapy Chemotherapy\u003c/p\u003e\u003cp\u003eRepeat resection for recurrent tumor\u003c/p\u003e\u003cp\u003eThird-Line Chemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRecurrence at 4 years post-op, survived 12 years since recurrence under surveillance\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNagata Y [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eType AB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLarge Cell Neuroendocrine Carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eExtended thymectomy Radiotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNo recurrence at 6 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWu SG [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eType B2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMucoepidermoid Carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e51y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThymectomy Chemotherapy Radiotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDisease-free for 12 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eZheng YW [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eType A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eThyroid Transcription Factor 1 (TTF-1) positive Adenocarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e53y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThoracoscopic mediastinal tumor resection, Partial lobectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDisease-free for 22 months after diagnosis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHosaka Y [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eType AB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePapillary Adenocarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThymectomy\u003c/p\u003e\u003cp\u003eRadiotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDisease-free for 11 years\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKitamura M [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eType AB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePapillary Adenocarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e81y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThoracoscopic mediastinal tumor resection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe diagnosis of thymoma coexisting with thymic carcinoma presents significant challenges and requires a comprehensive evaluation that integrates imaging studies, pathological findings, and clinical manifestations. Imaging studies, such as CT scans, are essential for the initial detection of mediastinal masses and may provide clues to the potential malignancy of a lesion.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] However, these imaging modalities often lack the specificity to distinguish between different tumor types. In this case, the irregular, lobulated morphology of the mass and the presence of calcifications raised suspicion of malignancy, but the exact nature of the tumor could not be determined preoperatively. Thymomas and thymic carcinomas may be asymptomatic or present with symptoms such as cough, chest pain, and dyspnea. Thymic carcinoma is usually more aggressive and more likely to metastasize to distant sites. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] Pathological examination and immunohistochemical staining are indispensable for confirming the diagnosis. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] In this case, the distinct immunohistochemical profiles of the two tumor components (lymphocytes positive for TdT, CD5, and CD1a, the epithelial cells positive for CK5/6 and P63 in thymoma versus CK5/6, CK7, CK8/18 and CEA positivity in adenocarcinoma) and distinct Ki67 proliferation indices (80% in thymoma hostpot areas vs. 30% in adenocarcinoma) were critical for establishing the diagnosis of AB-type thymoma coexisting with thymic adenocarcinoma. For the diagnosis of coexisting tumors, pathological examination is crucial, as imaging studies may not be able to fully differentiate between the two types of tumors.\u003c/p\u003e\u003cp\u003eThe coexistence of thymic carcinoma and thymoma presents a complex clinical scenario, necessitating careful evaluation of their interplay and appropriate management strategies. Complete surgical resection is generally considered the primary treatment modality, as it offers the best chance for cure, especially for localized tumors. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] However, adjuvant therapies such as chemotherapy and radiation therapy may be necessary, particularly for the more aggressive components of the tumor. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Radiotherapy may be administered after surgery, but it requires meticulous planning and execution to prevent harm to adjacent tissues. In this case, the patient underwent complete resection of the tumor, and no signs of recurrence or metastasis were observed within four months of follow-up. However, given the potential for recurrence, long-term follow-up is essential. Thymic adenocarcinoma is associated with a poorer prognosis compared to thymoma, and patients require close monitoring for any signs of disease progression. The patient is currently under close follow-up to monitor for recurrence.\u003c/p\u003e\u003cp\u003eThe patient's long-term smoking history raises questions about the potential role of smoking in the development of thymic malignancies. Smoking is a well-known risk factor for various cancers, and it may contribute to the development of thymic tumors through chronic inflammation and the induction of genetic mutations. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] However, the specific mechanisms linking smoking to coexisting AB-type thymoma and thymic adenocarcinoma remain to be elucidated. Further research is needed to clarify this association.\u003c/p\u003e\u003cp\u003eFuture research should focus on exploring the molecular mechanisms underlying the development of thymoma coexisting with thymic carcinoma. This includes investigating potential genetic and epigenetic alterations that may contribute to tumor heterogeneity. Additionally, the establishment of larger case series and registries will help improve our understanding of the clinical behavior and optimal management strategies for these rare tumors.\u003c/p\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eTumors with coexisting AB-type thymoma and thymic adenocarcinoma in the anterior mediastinum are challenging to diagnose preoperatively and require pathological and immunohistochemical confirmation. This case emphasizes the importance of considering tumor heterogeneity in the same anterior mediastinal masses. As more cases are reported, our understanding of these rare tumors will improve, leading to better clinical guidelines.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Jining First People\u0026apos;s Hospital. Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report and accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no financial support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the Radiology Department and the Pathology Group and Institute of Thoracic Tumor Research for providing the pathologic investigations and CT scan images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u0026nbsp;\u003c/strong\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBaoxiang Pei was involved in data collection, study design, analysis, preparation, and review of manuscript. Zhiliang Hu and Fen Pan were involved in data collection and review of manuscript. All authors contributed to the article and approved the submitted version.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMarx A, Chan JKC, Chalabreysse L, Dacic S, Detterbeck F, French CA, et al. The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial, Germ Cell, and Mesenchymal Tumors? J Thorac Oncol. 2022;17(2):200\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePDQ Adult Treatment Editorial Board. Thymoma and Thymic Carcinoma Treatment (PDQ\u0026reg;): Health Professional Version. 2024 Oct 25. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002\u0026ndash;.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAhmad U, Yao X, Detterbeck F, Huang J, Antonicelli A, Filosso PL, et al. Thymic carcinoma outcomes and prognosis: results of an international analysis. J Thorac Cardiovasc Surg. 2015;149(1):95\u0026ndash;100. 101.e1-2.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShiono A, Fujino T, Kaira K, Kato T, Yasuda M, et al. Primary thymic adenocarcinoma with an aggressive clinical course: An autopsy case showing signet ring cell-like features. Thorac Cancer. 2020;11(12):3609\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSuster S, Moran CA. Primary thymic epithelial neoplasms showing combined features of thymoma and thymic carcinoma. A clinicopathologic study of 22 cases. Am J Surg Pathol. 1996;20(12):1469\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWeissferdt A. Combined Thymic Epithelial Neoplasms - a Review. Int J Surg Pathol. 2023;31(6):917\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJiang Y, Liu Y, Shi X, Mao X, Zhao Y, Fan C. An unusual combined thymic carcinoma composed of squamous cell carcinoma and type AB thymoma: a rare case report. Diagn Pathol. 2017;12(1):9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOhue Y, Matsuoka S, Kumeda H, Agatsuma H, Hyougotani A, Toishi M, et al. Development of combined thymic carcinoma and thymoma in an extrathymic lesion during long follow-up for recurrent thymoma. Mol Clin Oncol. 2016;4(2):139\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNagata Y, Ohno K, Utsumi T, Sasaki Y, Suzuki Y. Large cell neuroendocrine thymic carcinoma coexisting within large WHO type AB thymoma. Jpn J Thorac Cardiovasc Surg. 2006;54(6):256\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlmuqbil S, AlHarbi A, Alzouri FS, Elbawab HY, Alsafwani NS, Alkhunaizy Z. Primary Thymic Hodgkin Lymphoma Coexisting with Thymoma and Myasthenia Gravis: A Case Report. Am J Case Rep. 2023;24:e941792.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMiller BS, Rusinko RY, Fowler L. Synchronous thymoma and thymic carcinoid in a woman with multiple endocrine neoplasia type 1: case report and review. Endocr Pract. 2008;14(6):713\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu SG, Li Y, Li B, Tian XY, Li Z. Unusual combined thymic mucoepidermoid carcinoma and thymoma: a case report and review of literature. Diagn Pathol. 2014;9:8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZheng YW, Bai LL, Jiang GY, Lin XY, Liu Y, Xu HT. Thymic adenocarcinoma accompanied by type A thymoma and pulmonary minimally invasive adenocarcinoma and harboring distinct gene alterations: A case report. Med (Baltim). 2021;100(15):e25254.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHosaka Y, Tsuchida M, Umezu H, Eimoto T, Hashimoto T, Shinohara H, et al. 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Treasure Island (FL): StatPearls Publishing; 2025\u0026amp;#8211.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTartarone A, Lerose R, Lettini AR, Tartarone M. Current Treatment Approaches for Thymic Epithelial Tumors. Life (Basel). 2023;13(5):1170.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJeong JH, Pyo JS, Kim NY, Kang DW. Diagnostic Roles of Immunohistochemistry in Thymic Tumors: Differentiation between Thymic Carcinoma and Thymoma. Diagnostics (Basel). 2020;10(7):460.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFalkson CB, Vella ET, Ellis PM, Maziak DE, Ung YC, Yu E. Surgical, Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Systematic Review. J Thorac Oncol. 2023;18(3):299\u0026ndash;312.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEriksson M, Kaerlev L, Johansen P, Afonso N, Ahrens W, Costa-Pereira A, et al. Tobacco smoking and alcohol consumption as risk factors for thymoma - A European case-control study. Cancer Epidemiol. 2019;61:133\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYanagiya M, Matsumoto J, Kawahara T, Yamaguchi H, Nagayama K, Anraku M, et al. Influence of Smoking and Histologic Subtype on Developing Extrathymic Malignancy in Thymoma Patients. Ann Thorac Surg. 2019;107(5):1532\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Thymic epithelial tumors, AB-type thymoma, Thymic adenocarcinoma, combined thymic tumors, Immunohistochemical staining","lastPublishedDoi":"10.21203/rs.3.rs-7083176/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7083176/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Thymic epithelial tumors are rare, with AB-type thymoma coexisting with thymic adenocarcinoma being particularly exceptional. Fewer than 50 cases of combined thymic tumors in the same anterior mediastinal mass have been reported, predominantly involving thymoma combined with squamous cell carcinoma or neuroendocrine tumors. This case report highlights an extremely rare occurrence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e: A 65-year-old female with a 40-year smoking history presented with a mediastinal mass detected on routine chest computed tomography (CT). Imaging revealed a 6.4cm×4.2cm irregular, lobulated mass in the anterior mediastinum. The patient underwent successful resection via single-port video-assisted thoracoscopic surgery. Pathological examination and immunohistochemical staining confirmed a tumor composed of AB-type thymoma and thymic adenocarcinoma. The thymoma component showed lymphocytes positive for terminal deoxynucleotidyl transferase (TdT), CD5, and CD1a, while the epithelial cells were positive for CK5/6 and P63, with a Ki67 proliferation index of approximately 80% in hostpot areas. The adenocarcinoma component was positive for CK7, CK8/18, CK5/6, CK19, and CEA (occasionally), with a Ki67 proliferation index of approximately 30%. No tumor cells were detected in the anterior superior mediastinal lymph nodes (0/2). The patient has been followed up for 4 months postoperatively and remains disease-free.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: This case emphasizes the importance of suspecting tumor heterogeneity in mediastinal masses and establishing a definitive diagnosis through pathological and immunohistochemical analysis. As more cases are reported, our understanding of these rare tumors will improve.\u003c/p\u003e","manuscriptTitle":"A Rare Case of Thymic Epithelial Tumor: AB-Type Thymoma coexisting with Thymic Adenocarcinoma and Review of literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-05 06:42:11","doi":"10.21203/rs.3.rs-7083176/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"48ec7529-86a7-4e96-9feb-c481d8a2c288","owner":[],"postedDate":"August 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-08T09:39:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-05 06:42:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7083176","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7083176","identity":"rs-7083176","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}