Clinical and pathological analysis of atypical type A thymoma_West China Medical Journal

Authors：

WANG Yan , LIU Bingshi , SONG Siyang , WANG Yuxuan ,  WANG Weiya

Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

WANG Weiya, Email: wangweiya@scu.edu.cn

Keywords：

Thymoma; atypical type A thymoma; clinicopathological features; GTF2I gene; prognostic analysis

DOI：

10.7507/1002-0179.202502164

Video：

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Objective To compare the differences in clinicopathological features, molecular phenotypes, and prognosis between atypical type A thymoma (AAT) and classic type A thymoma (TAT), and to clarify the aggressive nature of AAT. Methods The data of AAT patients (AAT group) and classic TAT patients (TAT group) who underwent surgical resection for thymoma at West China Hospital of Sichuan University between January 2016 and November 2024 were retrospectively collected. Comparisons on the clinical data, histopathology, immunohistochemistry (CD20, Ki67), GTF2I mutation status, and survival outcomes were performed between the two groups. Results A total of 53 patients were enrolled, including 22 in the AAT group and 31 in the TAT group. There was no significant difference in age, sex, or initial presenting symptoms between the two groups (P>0.05). Compared with the TAT group, the AAT group had larger tumors [(5.6±2.7) vs. (4.1±2.0) cm, P=0.043], a lower proportion of Masaoka stage Ⅰ (31.6% vs. 61.3%, P=0.041), and worse survival outcomes [progression-free survival: hazard ratio (HR)=0.046, 95% confidence interval (CI) (0.23, 0.89), P=0.004; overall survival: HR=0.36, 95%CI (0.19, 0.69), P=0.013]. Pathologically, the AAT group showed more mitotic figures (mean 6/2 mm²), and tumor necrosis was observed in 45.5% of cases. There was no statistically significant difference in the CD20 expression rate (20.0% vs. 41.9%), Ki67 index [(11.0±6.0)% vs. (8.0±6.9)%], or GTF2I mutation rate (86.7% vs. 92.3%) between the two groups (P>0.05). Conclusions AAT is a subtype of TAT with distinct aggressive pathological features, including higher mitotic activity, a tendency for necrosis, and a greater propensity for recurrence and metastasis. Pathological diagnosis should integrate morphology and molecular testing to guide more aggressive treatment and follow-up strategies.

1.	de Jong WK, Blaauwgeers JL, Schaapveld M, et al. Thymic epithelial tumours: a population-based study of the incidence, diagnostic procedures and therapy. Eur J Cancer, 2008, 44(1): 123-130.
2.	Filosso PL, Yao X, Ruffini E, et al. Comparison of outcomes between neuroendocrine thymic tumours and other subtypes of thymic carcinomas: a joint analysis of the European Society of Thoracic Surgeons and the International Thymic Malignancy Interest Group. Eur J Cardiothorac Surg, 2016, 50(4): 766-771.
3.	Barnes L, Eveson JW, ReicharTP, et al. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press, 2004.
4.	Chen G, Marx A, Chen WH, et al. New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer, 2002, 95(2): 420-429.
5.	Chalabreysse L, Roy P, Cordier JF, et al. Correlation of the WHO schema for the classification of thymic epithelial neoplasms with prognosis: a retrospective study of 90Tumors. Am J Surg Pathol, 2002, 26(12): 1605-1611.
6.	Nonaka D, Rosai J. Is there a spectrum of cytologic atypia in type A thymomas analogous to that seen in type B thymomas? A pilot study of 13 cases. Am J Surg Pathol, 2012, 36(6): 889-894.
7.	Marx A, Ströbel P, Badve SS, et al. ITMIG consensus statement on the use of the WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting. J Thorac Oncol, 2014, 9(5): 596-611.
8.	WHO Classification of Tumours Editorial Board. Thoracic tumours: WHO classification of tumours. 5th ed. Geneva: World Health Organization, 2021.
9.	Bernard C, Frih H, Pasquet F, et al. Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev, 2016, 15(1): 82-92.
10.	Marx A, Willcox N, Leite MI, et al. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity, 2010, 43(5/6): 413-427.
11.	汪昉睿, 庞烈文, 傅剑华, 等. 合并重症肌无力的胸腺瘤患者术后生存的初步分析——ChART 数据库回顾性结果. 中国肺癌杂志, 2016, 19(7): 418-424.
12.	Wang F, Pang L, Fu J, et al. Postoperative survival for patients with thymoma complicating myasthenia gravis-preliminary retrospective results of the ChART database. J Thorac Dis, 2016, 8(4): 711-717.
13.	Liang X, Lovell MA, Capocelli KE, et al. Thymoma in children: report of 2 cases and review of the literature. Pediatr Dev Pathol, 2010, 13(3): 202-208.
14.	Grajkowska W, Matyja E, Kunicki J, et al. AB Thymoma with atypical type A component with delayed multiple lung and brain metastases. J Thorac Dis, 2017, 9(9): E808-E814.
15.	Petrini I, Meltzer PS, Kim IK, et al. A specific missense mutation in occurs at high frequency in thymic epithelial tumors. Nat Genet, 2014, 46(8): 844-849.
16.	Feng Y, Lei Y, Wu X, et al. GTF2I mutation frequently occurs in more indolent thymic epithelial tumors and predicts better prognosis. Lung Cancer, 2017, 110: 48-52.
17.	Higuchi R, Goto T, Hirotsu Y, et al. Primary driver mutations in specific to the development of thymomas. Cancers (Basel), 2020, 12(8): 2032.
18.	Radovich M, Pickering CR, Felau I, et al. The integrated genomic landscape of thymic epithelial tumors. Cancer Cell, 2018, 33(2): 244-258.
19.	Wells K, Lamrca A, Papaxoinis G, et al. Unique correlation between mutation and spindle cell morphology in thymomas (type A and AB thymomas). J Clin Pathol, 2023, 76(7): 463-466.
20.	Qin L, Wang F, Chen L, et al. Rare atypical type A thymoma: a case report and literature review. Diagn Pathol, 2024, 19(1): 145.
21.	张波, 朱伟, 许萍榕, 等. 不典型 A 型胸腺瘤临床病理学分析. 诊断病理学杂志, 2024, 31(3): 273-274.
22.	Hirai M, Suzuki M, Imoto t, et al. Atypical type A thymoma component identified by pulmonary metastasectomy 11 years after surgery of type AB thymoma. Respir Med Case Rep, 2023, 46: 101944.
23.	Yanagiya M, Horiuchi H, Hiyama N, et al. Histopathological heterogeneity in an atypical type A thymoma variant with pulmonary metastases. Pathol Int, 2021, 71(6): 438-440.
24.	Jimbo N, Tateyama H, Komatsu M, et al. A case of type AB thymoma with atypical histological features: is atypical type AB thymoma an acceptable variant of thymoma?. Pathol Int, 2021, 71(4): 272-274.
25.	Yanagiya M, Hamaya H, Matsuzaki H, et al. Atypical type A thymoma variant manifesting polymyalgia rheumatica. Ann thorac Surg, 2020, 110(4): e253-e255.
26.	Chiappetta M, Marino M, Facciolo F. Unique case of atypical type A thymoma with vertebral metastasis and high 18-fluorodeoxyglucose avidity. ANZ J Surg, 2019, 89(10): E450-E451.
27.	Shen X, Jin Y, Shen L, et al. Thymoma and thymic carcinoma associated with multilocular thymic cyst: a clinicopathologic analysis of 18 cases. Diagn Pathol, 2018, 13(1): 41.
28.	Kawakita N, Kondo K, Toba H, et al. A case of atypical type A thymoma with vascular invasion and lung metastasis. Gen thorac Cardiovasc Surg, 2018, 66(4): 239-242.
29.	Hashimoto M, Tsukamoto Y, Matsuo S, et al. Lung metastases in an atypical type A thymoma variant. J Thorac Dis, 2017, 9(9): E805-E807.
30.	Bürger T, Schaefer IM, Küffer S, et al. Metastatic type A thymoma: morphological and genetic correlation. Histopathology, 2017, 70(5): 704-710.
31.	苏运超, 底锦熙, 笪冀平. 不典型 A 型胸腺瘤临床病理分析. 中华病理学杂志, 2017, 46(5): 314-317.
32.	Hashimoto M, Shimizu S, Takuwa T, et al. A case of atypical type A thymoma variant. Surg Case Rep, 2016, 2(1): 116.
33.	Weis CA, Yao X, Deng Y, et al. The impact of thymoma histotype on prognosis in a worldwide database. J Thorac Oncol, 2015, 10(2): 367-372.
34.	Altshuler E, Mathavan A, Mathavan A, et al. Clinical characteristics, prognostic factors, and long-term outcomes associated with epithelial malignancies of the thymus: a 20-year single-institution experience. Cancer Rep (Hoboken), 2023, 6(3): e1750.
35.	Weksler B, Lu B. Alterations of the immune system in thymic malignancies. J Thorac Oncol, 2014, 9(9 Suppl 2): S137-142.
36.	Detterbeck FC. Clinical value of the WHO classification system of thymoma. Ann thorac Surg, 2006, 81(6): 2328-2334.
37.	Jain RK, Mehta RJ, Henley JD, et al. WHO types A and AB thymomas: not always benign. Mod Pathol, 2010, 23(12): 1641-1649.
38.	Green AC, Marx A, Ströbel P, et al. Type A and AB thymomas: histological features associated with increased stage. Histopathology, 2015, 66(6): 884-891.
39.	Vladislav IT, Gökmen-Polar Y, Kesler KA, et al, The role of histology in predicting recurrence of type A thymomas: a clinicopathologic correlation of 23 cases. Mod Pathol, 2013, 26(8): 1059-1064.
40.	Roden AC, Yi ES, Jenkins SM, et al. Diagnostic significance of cell kinetic parameters in World Health Organization type A and B3 thymomas and thymic carcinomas. Hum Pathol, 2015, 46(1): 17-25.
41.	王誉萱, 王威亚. 不典型 A 型胸腺瘤临床病理特征及研究进展. 华西医学, 2023, 38(6): 943-946.
42.	Pan CC, Chen WY, Chiang H. Spindle cell and mixed spindle/lymphocytic thymomas: an integrated clinicopathologic and immunohistochemical study of 81 cases. Am J Surg Pathol, 2001, 25(1): 111-120.
43.	杜军, 周晓军, 印洪林, 等. CD20 在胸腺瘤中的表达及其临床病理意义. 中华病理学杂志, 2010, 39(9): 611-614.
44.	Okumura M, Ohta M, Tateyama H, et al. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer, 2002, 94(3): 624-632.

1. de Jong WK, Blaauwgeers JL, Schaapveld M, et al. Thymic epithelial tumours: a population-based study of the incidence, diagnostic procedures and therapy. Eur J Cancer, 2008, 44(1): 123-130.
2. Filosso PL, Yao X, Ruffini E, et al. Comparison of outcomes between neuroendocrine thymic tumours and other subtypes of thymic carcinomas: a joint analysis of the European Society of Thoracic Surgeons and the International Thymic Malignancy Interest Group. Eur J Cardiothorac Surg, 2016, 50(4): 766-771.
3. Barnes L, Eveson JW, ReicharTP, et al. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press, 2004.
4. Chen G, Marx A, Chen WH, et al. New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer, 2002, 95(2): 420-429.
5. Chalabreysse L, Roy P, Cordier JF, et al. Correlation of the WHO schema for the classification of thymic epithelial neoplasms with prognosis: a retrospective study of 90Tumors. Am J Surg Pathol, 2002, 26(12): 1605-1611.
6. Nonaka D, Rosai J. Is there a spectrum of cytologic atypia in type A thymomas analogous to that seen in type B thymomas? A pilot study of 13 cases. Am J Surg Pathol, 2012, 36(6): 889-894.
7. Marx A, Ströbel P, Badve SS, et al. ITMIG consensus statement on the use of the WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting. J Thorac Oncol, 2014, 9(5): 596-611.
8. WHO Classification of Tumours Editorial Board. Thoracic tumours: WHO classification of tumours. 5th ed. Geneva: World Health Organization, 2021.
9. Bernard C, Frih H, Pasquet F, et al. Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev, 2016, 15(1): 82-92.
10. Marx A, Willcox N, Leite MI, et al. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity, 2010, 43(5/6): 413-427.
11. 汪昉睿, 庞烈文, 傅剑华, 等. 合并重症肌无力的胸腺瘤患者术后生存的初步分析——ChART 数据库回顾性结果. 中国肺癌杂志, 2016, 19(7): 418-424.
12. Wang F, Pang L, Fu J, et al. Postoperative survival for patients with thymoma complicating myasthenia gravis-preliminary retrospective results of the ChART database. J Thorac Dis, 2016, 8(4): 711-717.
13. Liang X, Lovell MA, Capocelli KE, et al. Thymoma in children: report of 2 cases and review of the literature. Pediatr Dev Pathol, 2010, 13(3): 202-208.
14. Grajkowska W, Matyja E, Kunicki J, et al. AB Thymoma with atypical type A component with delayed multiple lung and brain metastases. J Thorac Dis, 2017, 9(9): E808-E814.
15. Petrini I, Meltzer PS, Kim IK, et al. A specific missense mutation in occurs at high frequency in thymic epithelial tumors. Nat Genet, 2014, 46(8): 844-849.
16. Feng Y, Lei Y, Wu X, et al. GTF2I mutation frequently occurs in more indolent thymic epithelial tumors and predicts better prognosis. Lung Cancer, 2017, 110: 48-52.
17. Higuchi R, Goto T, Hirotsu Y, et al. Primary driver mutations in specific to the development of thymomas. Cancers (Basel), 2020, 12(8): 2032.
18. Radovich M, Pickering CR, Felau I, et al. The integrated genomic landscape of thymic epithelial tumors. Cancer Cell, 2018, 33(2): 244-258.
19. Wells K, Lamrca A, Papaxoinis G, et al. Unique correlation between mutation and spindle cell morphology in thymomas (type A and AB thymomas). J Clin Pathol, 2023, 76(7): 463-466.
20. Qin L, Wang F, Chen L, et al. Rare atypical type A thymoma: a case report and literature review. Diagn Pathol, 2024, 19(1): 145.
21. 张波, 朱伟, 许萍榕, 等. 不典型 A 型胸腺瘤临床病理学分析. 诊断病理学杂志, 2024, 31(3): 273-274.
22. Hirai M, Suzuki M, Imoto t, et al. Atypical type A thymoma component identified by pulmonary metastasectomy 11 years after surgery of type AB thymoma. Respir Med Case Rep, 2023, 46: 101944.
23. Yanagiya M, Horiuchi H, Hiyama N, et al. Histopathological heterogeneity in an atypical type A thymoma variant with pulmonary metastases. Pathol Int, 2021, 71(6): 438-440.
24. Jimbo N, Tateyama H, Komatsu M, et al. A case of type AB thymoma with atypical histological features: is atypical type AB thymoma an acceptable variant of thymoma?. Pathol Int, 2021, 71(4): 272-274.
25. Yanagiya M, Hamaya H, Matsuzaki H, et al. Atypical type A thymoma variant manifesting polymyalgia rheumatica. Ann thorac Surg, 2020, 110(4): e253-e255.
26. Chiappetta M, Marino M, Facciolo F. Unique case of atypical type A thymoma with vertebral metastasis and high 18-fluorodeoxyglucose avidity. ANZ J Surg, 2019, 89(10): E450-E451.
27. Shen X, Jin Y, Shen L, et al. Thymoma and thymic carcinoma associated with multilocular thymic cyst: a clinicopathologic analysis of 18 cases. Diagn Pathol, 2018, 13(1): 41.
28. Kawakita N, Kondo K, Toba H, et al. A case of atypical type A thymoma with vascular invasion and lung metastasis. Gen thorac Cardiovasc Surg, 2018, 66(4): 239-242.
29. Hashimoto M, Tsukamoto Y, Matsuo S, et al. Lung metastases in an atypical type A thymoma variant. J Thorac Dis, 2017, 9(9): E805-E807.
30. Bürger T, Schaefer IM, Küffer S, et al. Metastatic type A thymoma: morphological and genetic correlation. Histopathology, 2017, 70(5): 704-710.
31. 苏运超, 底锦熙, 笪冀平. 不典型 A 型胸腺瘤临床病理分析. 中华病理学杂志, 2017, 46(5): 314-317.
32. Hashimoto M, Shimizu S, Takuwa T, et al. A case of atypical type A thymoma variant. Surg Case Rep, 2016, 2(1): 116.
33. Weis CA, Yao X, Deng Y, et al. The impact of thymoma histotype on prognosis in a worldwide database. J Thorac Oncol, 2015, 10(2): 367-372.
34. Altshuler E, Mathavan A, Mathavan A, et al. Clinical characteristics, prognostic factors, and long-term outcomes associated with epithelial malignancies of the thymus: a 20-year single-institution experience. Cancer Rep (Hoboken), 2023, 6(3): e1750.
35. Weksler B, Lu B. Alterations of the immune system in thymic malignancies. J Thorac Oncol, 2014, 9(9 Suppl 2): S137-142.
36. Detterbeck FC. Clinical value of the WHO classification system of thymoma. Ann thorac Surg, 2006, 81(6): 2328-2334.
37. Jain RK, Mehta RJ, Henley JD, et al. WHO types A and AB thymomas: not always benign. Mod Pathol, 2010, 23(12): 1641-1649.
38. Green AC, Marx A, Ströbel P, et al. Type A and AB thymomas: histological features associated with increased stage. Histopathology, 2015, 66(6): 884-891.
39. Vladislav IT, Gökmen-Polar Y, Kesler KA, et al, The role of histology in predicting recurrence of type A thymomas: a clinicopathologic correlation of 23 cases. Mod Pathol, 2013, 26(8): 1059-1064.
40. Roden AC, Yi ES, Jenkins SM, et al. Diagnostic significance of cell kinetic parameters in World Health Organization type A and B3 thymomas and thymic carcinomas. Hum Pathol, 2015, 46(1): 17-25.
41. 王誉萱, 王威亚. 不典型 A 型胸腺瘤临床病理特征及研究进展. 华西医学, 2023, 38(6): 943-946.
42. Pan CC, Chen WY, Chiang H. Spindle cell and mixed spindle/lymphocytic thymomas: an integrated clinicopathologic and immunohistochemical study of 81 cases. Am J Surg Pathol, 2001, 25(1): 111-120.
43. 杜军, 周晓军, 印洪林, 等. CD20 在胸腺瘤中的表达及其临床病理意义. 中华病理学杂志, 2010, 39(9): 611-614.
44. Okumura M, Ohta M, Tateyama H, et al. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer, 2002, 94(3): 624-632.

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