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Revista Portuguesa de Pneumologia

versão impressa ISSN 0873-2159

Rev Port Pneumol v.13 n.4 Lisboa jul. 2007

 

Timomas malignos – A experiência do IPO do Porto e revisão da literatura

Malignant thymomas – The experience of the Portuguese Oncological Institute, Porto, and literature review

 

Berta Sousa1

António Araújo2

Teresina Amaro3

Isabel Azevedo4

Marta Soares5

Olga Sousa6

 

Resumo

Introdução: Os tumores epiteliais tímicos (TET), a maioria timomas, são neoplasias desenvolvidas a partir das células epiteliais do timo e constituem cerca de 30% das massas do mediastino anterior em adultos. Os timomas são constituídos por células sem características citológicas de malignidade, sendo o comportamento maligno determinado pela invasão da cápsula e estruturas adjacentes. Estes tumores apresentam um amplo espectro de características clínicas e morfológicas, e as pequenas séries de doentes conhecidas tornam difícil o estabelecimento de um tratamento standard.

Material e métodos: Efectuou-se um estudo retrospectivo dos doentes admitidos com diagnóstico de timoma no Instituto Português de Oncologia – Centro do Porto (IPO-Porto), de 1983 a 2004. Foram analisadas as suas características clínicas, classificação histológica segundo a OMS, o estadiamento de Masaoka, e a sua relação com as modalidades de tratamento. Procedeu-se à revisão dos registos clínicos destes doentes e revisão do material histológico para a classificação segundo critérios da OMS de 1999.

Resultados: No IPO-Porto, entre 1983 e 2004, foram tratados 28 doentes com TET. Destes, 21 eram timomas invasivos, sendo estes o objecto deste estudo. Dos dados demográficos salienta-se que eram 11 homens, 10 mulheres, com uma idade mediana de 55 anos (24-79 anos). A classificação histológica da OMS foi a seguinte: 2 doentes (9,5%) Tipo A, 6 (28,6%) tipo AB, 4 (19%) tipo B1, 2 (9,5%) tipo B2, 7 (33,4%) tipo B3. O estadiamento segundo Masaoka foi 9 doentes (42,8%) com estádio II, 6 (28,6%) com estádio III e 6 (28,6%) com estádio IVa. A maioria dos doentes apresentava sintomas locais à apresentação, com apenas 1 doente com diagnóstico de aplasia eritrocitária e 5 com Mastenia gravis (MG). Os 6 doentes submetidos apenas a ressecção cirúrgica completa não tiveram evidência de recorrência da doença (2 tipo A-II, 2 tipo AB-II, 1 tipo B1-II, 1 tipo B2-IVa), com follow-up variando entre 8 e 144 meses. 10 doentes com ressecção completa receberam tratamento adjuvante, 6 radioterapia (4 doentes B3-II, 2 doentes B3-III), 2 quimioterapia (AB-IVa) e 2 radioterapia e quimioterapia (B1-IVa, B2-III). Apenas os 2 doentes que efectuaram quimioterapia adjuvante recidivaram, aos 168 e 46 meses, e morreram aos 168 e 49 meses. Os restantes doentes que efectuaram tratamento adjuvante encontram-se sem evidência de doença. Dos 5 doentes com ressecção incompleta seguido de tratamento complementar (2 doentes AB-III, 2 B1-IVa, 1 B3-III), 3 morreram aos 11 meses (B3-III), aos 12 meses (B1-IVa) e aos 241 meses (AB-III), este último por MG.

Conclusões: Apesar de se tratar de uma pequena série, os factores preditivos de mau prognóstico foram a ressecção incompleta, estádio avançado e o subtipo histológico B3. É necessário investigar o papel do tratamento adjuvante e neoadjuvante no grupo de doentes com doença avançada e subtipo histológico B3.

Palavras-chave: Tumores epiteliais tímicos, timomas, Miastenia gravis, quimioterapia, radioterapia

 

Abstract

Introduction: Epithelial thymic tumours (ETT), which comprise the majority of thymomas, are neoplasias developed from the epithelial cells of the thymus and constitute around 30% of anterior mediastinal masses in adults. Thymomas consist of cells with no cytological characteristics of malignity; malignant behaviour is determined by invasion of the capsule and adjacent structures. These tumours present a broad spectrum of clinical and morphological characteristics and the small series of known patients makes establishing a standard treatment difficult.

Material and methods: A retrospective study was made into thymoma diagnosed patients admitted to the Portuguese Oncology Institute in Porto (IPOPorto) from 1983 to 2004. Clinical characteristics were analysed and a histological classification made in accordance with World Health Organization criteria, Masaoka staging, and their relation to treatment methods. A review of the clinical records of these patients was then made, as well as a review of histological material for classification in line with 1999 WHO criteria.

Results: Twenty-eight ETT patients were treated at the IPO-Porto between 1983 and 2004. Of these, 21 had invasive thymomas and these are the subject of this study. Eleven subjects were male and 10 female, with a median age of 55 years (24-79 years). The WHO histological classification was as follows: 2 patients (9.5%) type A, 6 (28.6%) type AB, 4 (19%) type B1, 2 (9.5%) type B2, 7 (33.4%) type B3. Masaoka staging was 9 patients (42.8%) with stage II, 6 (28.6%) with stage III and 6 (28.6%) with stage IVa. The majority of patients had local symptoms, with only one subject diagnosed with erythrocyte aplasia and five with Myasthenia Gravis (MG). The 6 patients who were given complete surgical resection only showed no evidence of disease recurrence (2 type A-II, 2 type AB-II, 1 type B1-II, 1 type B2- IVa), with follow-up from 8-144 months. Ten patients with complete resection received adjuvant treatment; 6 radiotherapy (4 B3-II patients, 2 B3-III patients), 2 chemotherapy (AB-IVa) and 2 chemo and radiotherapy (B1-IVa, B2-III). Only the 2 patients who underwent adjuvant chemotherapy relapsed, at 168 and 46 months, dying at 168 and 49 months, respectively. The remaining patients who were given adjuvant treatment did not present signs of disease. Of the 5 subjects having incomplete resection followed by complementary treatment (2 AB-III patients, 2 B1-IVa patients, 1 B3-III patient), 3 died, at 11 months (B3-III), 12 months (B1-IVa) and 241 months (AB-III), the latter with MG.

Conclusions: Predictive factors of bad prognosis here were incomplete resection, advanced staging and B3 histological subtype, the smallness of this series notwithstanding. It is necessary to investigate the role of adjuvant and neoadjuvant treatment in a group of subjects with advanced disease of the B3 histological subtype.

Key-words: Epithelial thymic tumours, thymomas, Myasthenia gravis, chemotherapy, radiotherapy.

 

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Bibliografia / Bibliography

1. Mullen B, Richardson J. Primary anterior mediastinal tumors in children and adults. Ann Thorac Surg 1986; 42:338-45.        [ Links ]

2. Rosai J, Sobin L. Histological typing of tumors of the thymus. Em World Health Organization international histological classification of tumors. 2nd edition. New York, NY: Springer-Verlag, 1999.

3. Yagi K, Hirata T, Fukuse T, et al. Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded. Ann Thorac Surg 1996;61:521-4.

4. Johnson B, Eng T, Giaccone G, Thomas C. Thymoma: Update for the new milleniun. The Oncologist 2001; 6 (3): 239.

5. Goldel N, Boning L, Fredrik A, Holzel D, Hartenstein R, Wilmanns W. Chemotherapy of invasive thymoma. A retrospective study of 22 cases. Cancer 1989; 63 (8):1493-500.

6. Evans W, Thompson D, Simpson W, Feld R, et al. Combination chemotherapy in invasive thymoma. Cancer 1980; 46: 1523-7.

7. Loehrer P, Kim K, Aisner C, Livingstone R, Einhorn L, et al. Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. J Clin Oncol 1994;12:1164.

8. Loehrer PJ SR, Chen M, Kim KM, et al. Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an intergroup trial. J Clin Oncol 1997;15:3093.

9. Kim E, Putnam J, Komaki R, Walsh G, Ro J, Shin H, Truong M, et al. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical ressection, radiation therapy, and consolidation chemotherapy for unresectable malignat thymoma: final report. Lung Cancer 2004; 44: 369-79.

10. Bretti S, Berruti A, Loddo C, Sperone P, Casadio C, et al. Multimodal management of stages III-IVa malignat thymoma. Lung Cancer 2004; 44: 69-77.

11. Davis RD, Oldham HN, Sabiston DC. Primary cysts and neoplasm of the mediastinum: recent changes in clinical presentation, methods of diagnosis, management, and results. Ann Thorac Surg 1987; 44:229.

12. Azarow KS, Pearl RH, Zurcher R, Edwards FH, Cohen AJ. Primary mediastinal masses: a comparison of adult and pediatric populations. J Thorac Cardiovasc Surg 1993; 106: 67.

13. Thomas CR Jr, Wright CD, Loeher PJ Sr. Thymoma: state of the art. J Clin Oncol 1999; 17:2280.

14. Simpson I, Campbell PE. Mediastinal masses in childhood: a review from a pediatric pathologist´s point of view. Prog Pediatr Surg 1991; 27:93.

15. Engels EA, Pfeifer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer 2003; 105:546.

16. Patterson GA. Thymomas. Semin Thorac Cardiovasc Surg 1992;4:39.

17. Lewis JE, Wick MR, Scheithauer BW, Bernatz PE, Taylor WF. Thymoma. A clinicophatologic review. Cancer 1987; 60: 2727-43.

18. Bernatz PE, Harrison EG, Clagett OT. Thymoma: a clinicopathologic study. J Thorac Cardiovasc Surg 1961; 42: 424-44.

19. Maggi G, Giaccone G, Donadio M, Ciuffreda L, Dalesio O, Leria G, et al. A review of 169 cases, with particular reference to results of surgical treatment. Cancer 1968; 58: 765-76.

20. Wick MR. Assessing the prognosis of thymomas. Ann Thorac Surg 1990; 50:521-2.

21. Wilkins K, Sheikh E, Green R, Patel M, George S, et al. Clinical and pathologic predictors of survival in patients with thymoma; Ann Surgery 1999; 230 (4): 562-574.

22. Marino M, Muller-Hermelink HK. Thymoma and thymic carcinoma: relation of thymoma epithelial cells to the cortical and medullary differentiation of the thymus. Virchows Arch A Pathol Anat Histopathol 1985; 407: 119.

23. Pescarmona E, Rendima EA, Venuta F. Analyis of prognostic factors and clinicopathologic staging of thymomas. Ann Thorac Surg 1990; 50: 534-8.

24. Quintanilla- Martinez L, Wilkins EW Jr, Choi N, Efird J, Hug E, Harris NL. Thymoma. Histologic subclassification is an independent prognostic factor. Cancer 1994; 74: 606-17.

25. Lardinois D, Rechsteiner R. Prognostic relevance of Masaoka and Muller- Hermelink classification in patients with thymic tumors. Ann Thorac Surg 2000; 69: 1550-5.

26. Kornstein MJ, Curran WJ Jr, Turrisi AT 3rd, Brooks JJ. Cortical versus medullary thymomas: a useful morphologic distinction? Hum Pathol 1988; 19: 1335- 9.

27. Pan CC, Wu HP, Yang CF, Chen WY, Chiang H. The clinicopathologial correlation of epithelial subtyping in thmoma: a study of 112 consecutive cases. Hum Pathol 1994;25: 893-9.

28. Chen G, Marx A, Wen-Hu C, et al. New WHO histologic classification predicts prognosis of thymic epithelial tumors: A clinicopathologic study of 200 thymoma cases from China. Cancer 2002; 95: 420-9.

29. Okumura M, Ohta M, Miyoshi S, et al. Oncological significance of WHO histological thymoma classification. A clinical study based on 286 patients. Jpn Thorac Cardiovasc Surg 2002; 50: 189-94.

30. Okumura M, Miyoshi S et al. Clinical and Functional Significance of WHO Classification on Human Thymic Epithelial Neoplasms. A study of 146 Consecutive Tumors. Am J Surg Pathol 2001; 25(1): 103-10.

31. 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; 94:624-32.

32. Reno O, Papalia E, Maggi G, Oliaro A, Ruffini E, et al. World Organization histologic classification: an independent prognostic factor in resected thymomas. Lung Cancer 2005; 50: 59-66.

33. Chalabreysse L, Roy P, Cordier J, Loire R, Gamondes J, et al. Correlation of the WHO Schema for the classification of Thymic Epithelial Neoplasms With Prognosis. A retrospective Study of 90 Tumors. Am J Surg Pathol 2002; 26(12): 1605-11.

34. Nakagawa K, Asamura H, Matsuno Y. Thymoma: A clinicopathologic study based on the new World Health Organization classification. J Thorac Cardiovasc Surg 2003; 126:1134-40.

35. Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981; 48:2485.

36. Blumberg D, Jeffrey P, Weksler B, Delgado R, Rosai J, Bains M, et al. Thymoma: a multivariate analysis of factors predicting survival. Ann Thorac Surg 1995;60:903-13.

37. Kondo K, Monden Y. Therapy for thymic epithelial tumors: A clinical study of 1,320 patients from Japan. Ann Thorac Surg 2003;76:878-85.

38. Gamondes JP, Balawi A, Greenland T, et al. Seventeen years of surgical treatment of thymoma: Factors influencing survival. Eur J Cardiothorac Surg 1991; 5: 124-131.

39. Cowen D, Richaud P, Mortex F, et al. Thymoma: Results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. Radiother Oncol 34:9-16, 1995.

40. Strobel P, Bauer A, Puppe B, Kraushaar T, Krein A, et al. Tumor recurrence and Survival in Patients Treated for Thymomas and Thymic Squamous Cell carcinomas: A Retrospective Analysis. J Clin Oncol 2004, 22:1501-9.

41. Sperling B, Marschall J, Kennedy R, et al. A review of the clinical pathological findings in 65 cases. Can J Surg 2003; 46:37-42.

42. Whooley BP, Urschel JD, Antkowiak JG, et al. A 25-year thymoma treatment review. J Exp Clin Cancer Res 2000; 19:3-5.

43. Maggi G, Casadio C, Cavallo A, et al. Thymoma: results of 241 operated cases. Ann Thorac Surg 1991; 51:152.

44. Ciernik IF, Meier U, Lutolf UM. Prognostic factors and outcome of incompletely resecte invasive thymoma following radiation therapy. J Clin Oncol 1994;12:1484.

45. Liu H, Chen Y, Tzen C, Huang C, Chang C, et al. Debulking surgery for advanced thymoma. European Journal Surgical Oncology 2006, 32 (9): 1000-5.

46. Kirschner PA. Reoperation for thymoma: report of 23 cases. Ann Thorac Surg 1990;49:550.

47. Urgesi A, Monetti U, Rossi G, et al. Agressive treatmentof intrathoracic recurrrences of thymoma. Radiother Oncol 1992; 2:221.

48. Pollack A, Komaki R, Cox JD, et al. Thymoma: treatment and prognosis. Int J Radiat Oncol Biol Ohys 1992;23:1037.

49. Blumberg D, Port J, Webster B et al. Thymoma: a multivariate analysis of factors predicting survival. Ann Thorac Surg 1995; 60:908-14.

50. Robert D. Cameron, Patrick J Loehrer SR, Charles R, Thomas JR. Cancer Principles and Practice of Oncology, 7th edition, Lippincott Williams and Wilkins, 2005.

51. Ogawa K, Toita T, Kakinohana Y et al. Posoperative radiation therapy for completed resected invasive thymoma: prognostic value of pleural invasión for intrathoracic control. J Clin Oncol 1999; 29:474-8.

52. Myojin M, Choi NC, Wright CD et al. Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study. Int J Radiat Oncol Biol Phys 2000; 46:927-33.

53. Arakawa A, Yasunaga T, Saitoh Y et al. Radiation therapy of invasive thymoma. Int J Radiat Oncol Biol Phys.1990; 18:529-34.

54. Chachinian AP, Bhardwaj S, Meyer RJ, et al. Treatment of invasive or metastatic thymoma. Report of eleven cases. Cancer 1981; 47:1752.

55. Bogart J, Sagerman RH. High-dose hemithorax irradiation in a patient with recurrent thymoma: a study of pulmonary and cardiac radiation tolerance. Am J Clin Oncol 1999; 22:441.

56. Bonomi P, Finkelstein D, Aisner S, et al. EST 2582 phase II trial of cisplatin in metastatic or recurrent thymoma. Am J Clin Onco l1993; 16:342-5.

57. Harper P, Highly M, Rankin E, et al. The treatment of malignant thymoma with single agent ifosfamide. Br J Cancer 1991; 63(suppl13):7.

58. Tomiak EM, Evans WK. The role of chemotherapy in invasive thymoma: a review of the literature and considerations for future clinical trials. Crit Rev Oncol Hematol 1993;15:113.

59. Kikove C, Berghmans J, Noel H, Van de Merckt J. Dramatic response of recurrent invasive thymoma to high dose corticosteroids. Clin Oncol 1992;4:64.

60. Fornasiero A, Danilele O, Ghiotto C, et al. Chemotherapy for invasive thymoma: a 13 year experience. Cancer 1991; 68:30.

61. Giaccone G, Ardizzoni A, Kirkpatrick A, et al. cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma: a phase II study of the European Organization for research and treatment of lung cancer cooperative group. J Clin Oncol 1996;14:814-20.

62. Park HS, Shin DM, Lee JS, et al. Thymoma: a retrospective study of 87 cases. Cancer 1994; 73:2491.

63. Loeher P, Jiroutek M, Aisner S, et al. Phase II trial of etoposide (V), ifosfamide (I), plus cisplatin (P) in patients with advanced thymoma (T) or thymic carcinoma (TC): preliminary results from a ECOG coordinated intergroup trial. Proc Am Soc Clin Oncol 1998;17:30 (abst 118).

64. Campbell MG, Pollard R, et al. Complete response in metastatic malignat thymoma to cis-platinum, doxorubicin, and cyclophosphamide:a case report. Cancer 1981;48:1315.

65. Umswasdi T, Chiuten DF, Holoye P, et al. Cytoxan + adriamycin + cisplatin ± prednisone (CAP±prednisone) in treatment of malignant thymic tumors. Proc Am Soc Clin Oncol 1985;4:149.

66. Dy C, Calvo F, Mindan J, Aparicio L, Algarra S, et al. Undifferentiated epithelial-rich invasive malignat thymoma: complete response to cisplatin, vinblastine, and bleomycin theapy. J Clin Oncol 1988;6:536-42.

67. Rea F, Sartori F, Loy M Calabro F, Fornasiero A, et al. Chemotherapy and operation for invasive thymoma. J Cardiovasc Surg 1993;106:543.

68. Shin D., Walsh G, Komaki R, Putnam J, Nesbitt J et al. A multidisciplinary approach to therapy for unresectable malignat thymoma. Ann Inter Med 1998; 129 (2): 100-4.

69. Park H, Shin D, Lee J, Komaki R, Pollack A, et al. Thymoma a retrospective study of 87 cases. Cancer 1994;73(10):2491-8.

70. Highly M, Underhill C, Parnis F, Karapetis C, Rankin E. Treatment of invasive thymoma with single-agent ifosfamide. J Clin Oncol 1999;17(9):2737-44 .

71. Marco L, Franca M, Paolo D, Fulvio B, Andrea V, et al. Chemotherapy for Stage III and IVA Thymomas: A Single-Institution Experience with a Long Follow-up. Journal of Thoracic Oncology 2006; 1(4):308-13.

72. Loehrer P, Wang W, Johnson D, Ettinger D. Octreotide alone or with Prednisone in patients with advanced thymoma and thymic carcinoma: An Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol 2004; 22:293-9.

73. Palmieri G, Lastoria S, Colao A, Vergara E, Varrella P, Biondi E, et al. Successful treatment of a patient with a thymoma and pure red cell aplasia with octreotide plus prednisone. N Engl J Med 1997; 336:263-5.

74. Lin K, Nguyen B, Ettinger D, Chin B. Somatostatin receptor scintigraphy and somatostatin therapy in the evaluation and treatment of malignat thymoma. Clin Nucl Med 1999; 24:24-8.

75. Iwasaki Y, Ohsugi S, Takemura Y, Nagata K, Harada H, et al. Multidisciplinary Therapy Including High-Dose Chemotherapy Followed by Peripheral Blood Stem Cell Transplantation for Invasive Thymoma. Chest 2002; 122; 2249-52.

76. Gordon MS, Battiato LA, Gonin R, Harrison-Mann BC, Loehrer PJ. A phase II trial of subcutaneously administered recombinant human interleukin-2 in patients with relapse/refractory thymoma. J Immunother Emphasis Tumor Immunol 1995; 18(3):179-1284.

77. Schmidt- Wolf I, Muller-Hermelink H, Huhn D. Malignant thymoma: current status of classification and multimodality treatment. Ann Hematol 2003; 82:69-76.

78. Drachman DB. Medical Progress: Myasthenia gravis. N Engl J Med 1994; 330:1797-810.

79. Lopez-Cano M, Ponseti-Bosch J, Espin-Basany E, Sanchez-Garcia J, et al. Clinical and Pathologic Predictors of Outcome in Tymoma-Associated Myasthenia gravis. Ann Thorac Surg 2003; 76:1643-9.

80. De Perrot M, Liu J, Bril V, McRae K, et al. Prognostic Significance of thymomas in Patients with Myasthenia gravis. Ann Thorac Surg 2002; 74:658-62.

81. Bril V, Kojic J, Dhanani A. The long term clinical outcome of Myasthenia gravis in patients with thymoma. Neurology 1998; 51:1198-200.

 

1 Interna complementar de Oncologia Médica no IPOPFG-EPE / Medical Oncology Resident, IPOPFG-EPE

2Assistente Hospitalar Graduado de Oncologia Médica no IPOPFG-EPE / Specialist Medical Oncology Consultant , IPOPFG-EPE

3 Assistente Hospitalar de Anatomia Patológica no IPOPFG-EPE / Anatomic Pathology Consultant, IPOPFG-EPE

4Assistente Hospitalar de Oncologia Médica no IPOPFG-EPE / Medical Oncology Consultant, IPOPFG-EPE

5 Assistente Hospitalar de Radioterapia no IPOPFG-EPE / Radiotherapy Consultant, IPOPFG-EPE

 

Trabalho realizado no Instituto Português de Oncologia do Porto Francisco Gentil, EPE, nos serviços de Oncologia Médica (Director: Dr. José Leal da Silva), e de Anatomia Patológica (Director: Dr. Rui Henrique). / Study undertaken at the Portuguese Oncology Institute (IPO) Porto Francisco Gentil, EPE, Medical Oncology

(Director: Dr. José Leal da Silva), and Anatomic Pathology (Director: Dr. Rui Henrique) Units.

IPOPFG, EPE:

Rua Dr António Bernardino de Almeida

4200-072 Porto

Fax: 003515084008

 

Recebido para publicação/received for publication: 06.10.16

Aceite para publicação/accepted for publication: 07.02.22