{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T03:08:31Z","timestamp":1789528111412,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T00:00:00Z","timestamp":1705795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Thymomas are rare tumors of the anterior mediastinum with peculiar clinical and pathological features. They have been deeply analyzed by pioneer authors, who strictly linked their name to the main pathological and staging classifications. Before the latest edition of the WHO classification of thymic epithelial tumors, the history of thymoma pathological classification inherited the name of the pathologists who systematically addressed the issue, from Levine-Rosai to Muller-Hermelink. Similarly, the thymoma staging system is intimately related to the name of two surgeons, Masaoka and Koga, who historically dealt with this disease. More recently, the traditional tumor-nodes-metastasis (TNM) system has been developed for the staging of this condition, in a rational attempt to put thymomas in conformity with the other solid tumors. The efforts of the International Thymic Malignancies Interest Group (ITMIG) and the Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC) of the International Association for the Study of Lung Cancer (IASLC) resulted in the TNM classification of thymic tumors, which have been included in the eighth edition of the American Joint Committee on Cancer\u2019s (AJCC) Cancer Staging Manual. Herein, we report a narrative review of the evolution of the thymic epithelial tumors (TET) staging system and present a critical appraisal of the actual TNM classification compared with the historical Masaoka-Koga classification, with special focus on the proposal for the ninth edition of the TNM, expected in 2024.<\/jats:p>","DOI":"10.3390\/jcm13020610","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T11:36:41Z","timestamp":1705923401000},"page":"610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["TNM Staging System in Thymoma: A Critical Appraisal?"],"prefix":"10.3390","volume":"13","author":[{"given":"Marcello Carlo","family":"Ambrogi","sequence":"first","affiliation":[{"name":"Division of Thoracic Surgery, Cardiac, Thoracic, and Vascular Department, University of Pisa, 56127 Pisa, Italy"},{"name":"Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8538-1719","authenticated-orcid":false,"given":"Vittorio","family":"Aprile","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Cardiac, Thoracic, and Vascular Department, University of Pisa, 56127 Pisa, Italy"},{"name":"Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Lenzini","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Cardiac, Thoracic, and Vascular Department, University of Pisa, 56127 Pisa, Italy"},{"name":"Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-0974","authenticated-orcid":false,"given":"Diana","family":"Bacchin","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Cardiac, Thoracic, and Vascular Department, University of Pisa, 56127 Pisa, Italy"},{"name":"Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-5619","authenticated-orcid":false,"given":"Maria Giovanna","family":"Mastromarino","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Cardiac, Thoracic, and Vascular Department, University of Pisa, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8818-6553","authenticated-orcid":false,"given":"Stylianos","family":"Korasidis","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Cardiac, Thoracic, and Vascular Department, University of Pisa, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9909-6820","authenticated-orcid":false,"given":"Marco","family":"Lucchi","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Cardiac, Thoracic, and Vascular Department, University of Pisa, 56127 Pisa, Italy"},{"name":"Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.33590\/emjrespir\/10310358","article-title":"Thymomas and thymic carcinomas: A review on pathology, presentation, staging, treatment, and novel systemic therapies","volume":"5","author":"Miyamoto","year":"2017","journal-title":"EMJ Respir."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/j.athoracsur.2003.10.001","article-title":"Thymic tumors","volume":"77","author":"Detterbeck","year":"2004","journal-title":"Ann. Thorac. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.lungcan.2013.09.013","article-title":"Historical perspectives: The evolution of the thymic epithelial tumors staging system","volume":"83","author":"Filosso","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1093\/ajcp\/111.6.826","article-title":"Thymoma, atypical thymoma, and thymic carcinoma. A novel conceptual approach to the classification of thymic epithelial neoplasms","volume":"111","author":"Suster","year":"1999","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.21037\/med.2018.01.04","article-title":"The evolution of the histopathologic classification of thymic epithelial tumors","volume":"2","author":"Marino","year":"2018","journal-title":"Mediastinum"},{"key":"ref_6","first-page":"407","article-title":"Histologic typing of thymoma according to the new World Health Organization classification","volume":"11","author":"Dadmanesh","year":"2001","journal-title":"Chest Surg. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/S0022-5223(20)31934-6","article-title":"Thymoma: A clinicopathological study","volume":"42","author":"Bernatz","year":"1961","journal-title":"J. Thorac. Ardiovasc. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0003-4975(10)63498-4","article-title":"Tumors of the thymus and thymic region, I: Clinicopathological studies on thymomas","volume":"25","author":"Bergh","year":"1978","journal-title":"Ann. Thorac. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0003-4975(10)63114-1","article-title":"Thymoma: A continuing survey at the Massachusetts General Hospital","volume":"28","author":"Wilkins","year":"1979","journal-title":"Ann. Thorac. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1002\/1097-0142(19811201)48:11<2485::AID-CNCR2820481123>3.0.CO;2-R","article-title":"Follow-up study of thymomas with special reference to their clinical stages","volume":"48","author":"Masaoka","year":"1981","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1440-1827.1994.tb02936.x","article-title":"A review of 79 thymomas: Modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma","volume":"44","author":"Koga","year":"1994","journal-title":"Pathol. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/1097-0142(19911101)68:9<1984::AID-CNCR2820680923>3.0.CO;2-P","article-title":"A tentative tumor-node-metastasis classification of thymoma","volume":"68","author":"Yamakawa","year":"1991","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"727","DOI":"10.21037\/jtd.2016.03.22","article-title":"Comparison of the Masaoka-Koga staging and the International Association for the Study of Lung Cancer\/the International Thymic Malignancies Interest Group proposal for the TNM staging systems based on the Chinese Alliance for Research in Thymomas retrospective database","volume":"8","author":"Liang","year":"2016","journal-title":"J. Thorac. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1097\/JTO.0000000000000290","article-title":"The IASLC\/ITMIG thymic epithelial tumors staging project: Proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors","volume":"9","author":"Detterbeck","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S2692","DOI":"10.21037\/jtd.2018.08.36","article-title":"Clinical implication of the new TNM classification of thymic malignancies","volume":"10","author":"Detterbeck","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S304","DOI":"10.1097\/JTO.0b013e3181f20c05","article-title":"Staging system of thymoma","volume":"5","author":"Masaoka","year":"2010","journal-title":"J. Thorac. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12957-017-1283-4","article-title":"Evaluation of the new TNM-staging system for thymic malignancies: Impact on indication and survival","volume":"15","author":"Ried","year":"2017","journal-title":"World J. Surg. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.jtho.2023.09.002","article-title":"The IASLC Thymic Epithelial Tumors Staging Project: Proposal for a Stage Classification for the Forthcoming (9th) Edition of the TNM Classification of Malignant Tumors","volume":"18","author":"Ruffini","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S1569-9293(03)00265-2","article-title":"Thymoma needs a new staging system","volume":"3","author":"Asamura","year":"2004","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/cncr.10226","article-title":"The world health structures\/structures\/organization histologic classification system reflects the oncologic behavior of thymoma","volume":"94","author":"Okumura","year":"2002","journal-title":"Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/S0022-5223(03)00798-0","article-title":"Thymoma: A clinicopathologic study based on the new World Health Organization classification","volume":"126","author":"Nakagawa","year":"2003","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"926","DOI":"10.5858\/2008-132-926-EPATPE","article-title":"Evidence-based pathology and the pathologic evaluation of thymomas: Transcapsular invasion is not a significant prognostic feature","volume":"132","author":"Gupta","year":"2008","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/0003-4975(91)90478-9","article-title":"Thymoma: Results of 241 operated cases","volume":"51","author":"Maggi","year":"1991","journal-title":"Ann. Thorac. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/S0003-4975(00)01140-1","article-title":"Prognostic relevance of Masaoka and Mu\u00a8ller-Hermelink classification in patients with thymic tumors","volume":"69","author":"Lardinois","year":"2000","journal-title":"Ann. Thorac. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1097\/JTO.0000000000000482","article-title":"Modified Masaoka stage and size are independent prognostic predictors in thymoma and modified Masaoka stage is superior to histopathologic classifications","volume":"10","author":"Roden","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/jso.26593","article-title":"Prognostic factors for survival in advanced thymomas: The role of the number of involved structures","volume":"124","author":"Chiappetta","year":"2021","journal-title":"J. Surg. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.athoracsur.2018.08.071","article-title":"Nerve-Sparing Surgery in Advanced Stage Thymomas","volume":"107","author":"Aprile","year":"2019","journal-title":"Ann. Thorac. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/S0003-4975(03)01020-8","article-title":"Long-term outcome after multimodality treatment for stage III thymic tumors","volume":"76","author":"Venuta","year":"2003","journal-title":"Ann. Thorac. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.athoracsur.2015.04.059","article-title":"Surgical Outcomes of Patients With Stage III Thymoma in the Japanese Nationwide Database","volume":"100","author":"Yamada","year":"2015","journal-title":"Ann. Thorac. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0022-5223(99)70343-0","article-title":"Results of surgical treatment of thymomas with special reference to the involved organs","volume":"117","author":"Okumura","year":"1999","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ejcts.2010.11.026","article-title":"Surgical treatment of stage III thymic tumors: A multi-institutional review from four Italian centers","volume":"39","author":"Marulli","year":"2011","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/0003-4975(95)00669-C","article-title":"Thymoma: A multivariate analysis of factors predicting survival","volume":"60","author":"Blumberg","year":"1995","journal-title":"Ann. Thorac. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1002\/1097-0142(19871201)60:11<2727::AID-CNCR2820601125>3.0.CO;2-D","article-title":"Thymoma. A clinicopathologic review","volume":"60","author":"Lewis","year":"1987","journal-title":"Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.jtcvs.2005.07.026","article-title":"Predictors of recurrence in thymic tumors: Importance of invasion, World Health Organization histology, and size","volume":"130","author":"Wright","year":"2005","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1093\/ejcts\/ezt649","article-title":"European Association of Thoracic Surgeons (ESTS) Thymic Working Group. Tumours of the thymus: A cohort study of prognostic factors from the European Society of Thoracic Surgeons database","volume":"46","author":"Ruffini","year":"2014","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/j.jtho.2023.08.024","article-title":"The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Proposal for the T Component for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors","volume":"18","author":"Okumura","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1016\/S0003-4975(03)01017-8","article-title":"Lymphogenous and hematogenous metastasis of thymic epithelial tumors","volume":"76","author":"Kondo","year":"2003","journal-title":"Ann. Thorac. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S88","DOI":"10.1097\/JTO.0000000000000293","article-title":"The ITMIG\/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors","volume":"9","author":"Bhora","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jtho.2023.09.1447","article-title":"The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposals for the N and the M Components for the Forthcoming (9th) Edition of the TNM Classification of Malignant Tumors","volume":"19","author":"Fang","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jtcvs.2014.11.054","article-title":"Resection of thymoma should include nodal sampling","volume":"149","author":"Weksler","year":"2015","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.jtho.2019.11.013","article-title":"The International Association for the Study of Lung Cancer Thymic Tumors Staging Project: The Impact of the Eighth Edition of the Union for International Cancer Control and American Joint Committee on Cancer TNM Stage Classification of Thymic Tumors","volume":"15","author":"Ruffini","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/icvts\/ivx116","article-title":"Lymph node metastases in thymic malignancies: A Chinese Alliance for Research in Thymomas retrospective database analysis","volume":"25","author":"Gu","year":"2017","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1097\/JTO.0000000000000291","article-title":"Members of the Advisory Boards; Participating Institutions of the Thymic Domain. The IASLC\/ITMIG Thymic Epithelial Tumors Staging Project: Proposals for the N and M components for the forthcoming (8th) edition of the TNM classification of malignant tumors","volume":"9","author":"Kondo","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Pang, J., Xiu, W., and Ma, X. (2023). Application of Artificial Intelligence in the Diagnosis, Treatment, and Prognostic Evaluation of Mediastinal Malignant Tumors. J. Clin. Med., 12.","DOI":"10.3390\/jcm12082818"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Aprile, V., Lenzini, A., Lococo, F., Bacchin, D., Korasidis, S., Mastromarino, M.G., Guglielmi, G., Palmiero, G., Ambrogi, M.C., and Lucchi, M. (2021). Hyperthermic Intrathoracic Chemotherapy for Malignant Pleural Mesothelioma: The Forefront of Surgery-Based Multimodality Treatment. J. Clin. Med., 10.","DOI":"10.3390\/jcm10173801"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/icvts\/ivaa019","article-title":"Surgical treatment of pleural recurrence of thymoma: Is hyperthermic intrathoracic chemotherapy worthwhile?","volume":"30","author":"Aprile","year":"2020","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Chappuy, B., Drevet, G., Clermidy, H., Rosamel, P., Duruisseaux, M., Couraud, S., Grima, R., Soldea, V., Chalabreysse, L., and Tronc, F. (2022). Subtotal Pleurectomy with Intrathoracic Chemo Hyperthermia (HITHOC) for IVa Thymomas: De Novo Versus Recurrent Pleural Disease. Cancers, 14.","DOI":"10.3390\/cancers14205035"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Azenha, L.F., Deckarm, R., Minervini, F., Dorn, P., Lutz, J., and Kocher, G.J. (2021). Robotic vs. Transsternal Thymectomy: A Single Center Experience over 10 Years. J. Clin. Med., 10.","DOI":"10.3390\/jcm10214991"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e214","DOI":"10.1093\/ejcts\/ezt305","article-title":"The oncological feasibility and limitations of video-assisted thoracoscopic thymectomy for early-stage thymomas","volume":"44","author":"Kimura","year":"2013","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.jtho.2023.02.007","article-title":"Minimally Invasive Thymectomy Could Be Attempted for Locally Advanced Thymic Malignancies: A Real-World Study With Propensity Score-Matched Analysis","volume":"18","author":"Nakajima","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/j.athoracsur.2020.12.010","article-title":"Thymectomy in Myasthenic Patients with Thymoma: Killing Two Birds with One Stone","volume":"112","author":"Aprile","year":"2021","journal-title":"Ann. Thorac. Surg."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/2\/610\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:46:46Z","timestamp":1760104006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/2\/610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,21]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["jcm13020610"],"URL":"https:\/\/doi.org\/10.3390\/jcm13020610","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,21]]}}}