Treatment of invasive thymoma with myasthenia gravis: a case report responsive to azathioprine and methylprednisolone

The treatment of invasive thymomas associated with autoimmune diseases, such as myasthenia gravis (MG) and pure red cell aplasia, has not been established. In this paper, we report a 37-year-old patient with post thymectomy myasthenia gravis, who underwent subtotal resection of invasive thymoma with residual lesions of intrathoracic implants. He was treated with azathioprine (AZP) and methylprednisolone (MP). During two months from the start of this therapy, the clinical symptom was improved apparently and the recurrent tumor was reduced. Lasting 18 months of the treatment, he had to stop it because of the renal failure, but now he has no sign of the recurrence. Further studies with this combined regiments are warranted in the treatment of the invasive thymomas associated with autoimmune disease.     

Results of surgical treatment for thymoma based on 66 patients

Sixty-six patients with thymoma have undergone surgical treatment since 1965 and have been assessed from the viewpoint of clinical manifestations and prognosis. Thirty-one patients with encapsulated thymoma were treated with total surgical resection alone, and they had no postoperative tumor recurrence. With the exception of one patient who died of respiratory insufficiency on the fourth day after the operation, 34 patients with invasive thymoma were evaluated on the basis of their postoperative prognosis. Fifteen patients with invasive thymoma died from 1 1/2 months to 10 years, 1 month postoperatively; 9 died of local or metastatic tumor and 6 died of other diseases. Associated autoimmune diseases, as well as the invasive tendency of the tumors, apparently affected the prognosis. Ten-year survival rates of the patients who underwent surgical treatment were as follows: 61.6% for the total group, 74.3% for those with encapsulated thymoma, and 49.4% for those with invasive thymoma. In the surgical treatment for invasive thymomas, one should aim to resect the tumor totally, even though adjacent tissues are resected simultaneously. Even for the patient with total resection of invasive tumor, postoperative radiation should be required. Finally, if residual tumor must be left during the operation, postoperative radiation as well as anticancer chemotherapy should be aggressively scheduled, because postoperative distant metastasis may appear in these patients with residual thymoma.     

Role of positive selection of thymoma-associated T cells in the pathogenesis of myasthenia gravis

BACKGROUND: A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4(+)CD8(+) double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of alphabeta or gammadelta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event. MATERIALS AND METHODS: Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis. RESULTS: The average proportion of TCRalphabeta(+) cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher (P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCRalphabeta(+)CD69(+)CD4(+)CD8(-) cells in the myasthenic thymomas (8.22%) was significantly greater (P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCRalphabeta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas. CONCLUSIONS: The possible role of development of TCRalphabeta(+) T cells, especially the role of positive selection of TCRalphabeta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis.     

Results from surgical treatment for thymoma. 43 years of experience.

OBJECTIVE: The biological behavior of thymoma and its prognosis after surgical intervention remain still controversial. The efficacy of surgical treatment for thymoma was investigated by examining long-term follow-up data. SUBJECTS AND METHODS: Follow-up data for patients undergoing surgical resection of histopathologically-confirmed thymoma between 1954 and 1997 were obtained and were retrospectively analyzed. Clinical staging was based on Masaoka's staging system, and histological classification on Rosai's proposed criteria. RESULTS: Data for 140 patients were collected. Sixty-four patients had stage I, 32 had stage II, 28 had stage III, and 16 had stage IV thymoma. There were significant differences in survival between patients with stage I and stage III, stage I and stage IV and stage II and stage III disease, but not between those with stage I thymoma and stage II thymoma. No significant difference in survival was observed between the 56 patients with myasthenia gravis (MG) and the 84 without MG. The 38 patients classified as having a predominantly-epithelial thymoma had a poorer prognosis than the 41 with a predominantly-lymphocytic thymoma. Until 1975, there were four patients with stage I thymomas who later showed recurrence, compared with 21 among those with stage II, III and IV diseases. Since 1976, extended thymectomy with thymomectomy under median sternotomy has been adopted as the standard operation for a thymoma, and there has been no recurrence in stage I patients. CONCLUSIONS: Patients with stage III or IV invasive thymoma have a poorer prognosis and a higher recurrence rate than those with encapsulated thymoma, and patients with a predominantly-epithelial thymoma have a poorer prognosis than those with a predominantly-lymphocytic thymoma. Extended thymectomy with thymomectomy under median sternotomy can be considered as adequate treatment for a stage I thymoma. Myasthenia gravis does not appear to affect the prognosis of patients with a thymoma.     

Seventeen years of surgical treatment of thymoma: factors influencing survival

We report on 17 years experience of the surgical treatment of thymoma in 65 patients, 11 with and 54 without myasthenia gravis. Patients were staged using the French "GETT" classification; 38 were in stage I (no invasive tumor), 6 in stage II, 13 in stage III and 8 in stage IV. In 45 patients, surgical excision was total while the remaining 20 underwent partial resection only. Postoperative radiotherapy was given in 12 cases, and 17 received a combination of radiotherapy and chemotherapy. One patient was lost to follow up, but no operative death occurred in the series. The mean survival for all patients was 70 +/- 7 months, and the 5- and 10-year survival was 91% +/- 4% and 69% +/- 8%, respectively. Follow-up for the 47 patients still alive and 4 patients deceased from unrelated causes ranged from 1.5 to 180 months (mean 142 +/- 10 months). Our data indicate that the prognosis of thymoma relates to radiological discovery (P less than 0.01), total surgical resection (P less than 0.01) and stage of tumor (P less than 0.01). It is not influenced by age, sex, tumor cell type or the presence or absence of myasthenia gravis.     

Recurrent thymoma in patients with myasthenia gravis

One hundred sixty-six patients underwent operation for myasthenia gravis between 1977 and 1989. Thirty-eight patients had associated thymoma, registering stages I (n = 17), II (n = 9), III (n = 11), and IVa (n = 1) according to the classification of Masaoka and colleagues. Extended thymectomy was performed on 128 patients without thymoma; thymothymectomy, with resection of the anterior mediastinal fat and tissues adherent to the tumor, was performed in all patients with thymoma. There were no instances of early or late death. Neuromuscular function improved, and clinical myasthenic symptoms stabilized in almost all patients except 2 patients in stage III and 1 patient in stage IVa, who had an exacerbation of the myasthenic symptoms associated with recurrence of thymoma. All the recurrent tumors were on the pleura and could be resected. The suspected cause of recurrence is either dissemination of tumor cells as a result of operative manipulation or undetected disseminated foci that existed at the time of the first operation. The resections of the recurrent invasive thymomas localized on the pleura were easily performed and improved the myasthenic symptoms.     

Reoperation for thymoma: report of 23 cases

Twenty-three patients underwent reoperation for thymoma at intervals of 2 months to 17 years 10 months after the initial operation. There were no operative or hospital deaths. Myasthenia gravis occurred in 12 patients, but in only 2 was it a determinant for reoperation. The longest survival after reoperation is 12 years 9 months, and that patient is free from tumor. Four distinct surgical groups emerged, and their recognition provides an improved method of reporting and suggests a strategy for better overall management. Group 1 (n = 5) had completion of thymectomy (reoperation) after thymomectomy alone or after incomplete thymectomy. The interval was 2 months to 17 years 10 months. All 5 had myasthenia gravis. At reoperation, thymomas were found in 3 and a hyperplastic thymus in 2. Four are alive and tumor free 2 years to 8 years 2 months after reoperation. One died tumor free after 5 years. Group 2 (n = 8) had reoperation for recurrent thymoma after standard (presumably complete) resection. The interval was 2 years to 13 1/2 years. Four had myasthenia gravis. Four are alive 8 months to 5 years 8 months after reoperation, 3 without detectable tumor. Four died 3 years 3 months to 8 years 4 months after reoperation, 3 free from tumor. Group 3 (n = 8) underwent reoperation for initially unresectable thymoma after adjuvant treatment with chemotherapy, radiotherapy, or both. The interval was 3 months to 4 years 8 months. Three had myasthenia gravis. Six are alive 4 months to 4 years after reoperation, only 1 with tumor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunological function of thymoma and pathogenesis of paraneoplastic myasthenia gravis

Thymoma and thymic carcinoma are the representative tumors arising from the thymic epithelium. Thymoma is well known for association with autoimmune diseases including myasthenia gravis, suggesting its biological activity. Herein, recent progress in research of thymoma is reviewed with reference to its immunological function. Myasthenia gravis is frequently associated with WHO type B1 and B2 thymomas. These types of thymomas hold a significant number of CD4⁺CD8⁺ double-positive T cells, and at the same time, the neoplastic epithelial cells express HLA-DR molecules at a slightly reduced level compared with the normal thymus. The impaired expression of HLA-DR molecules in neoplastic epithelial cells of thymomas possibly affects positive selection of CD4⁺CD8⁻ single-positive T cells and may result in alteration of its repertoire. The function of thymoma neoplastic cells as the cortical epithelium of the thymus and the morphological resemblance of thymomas to the cortex suggest that thymoma is of cortical epithelial origin; this might imply that thymoma lacks the functional medulla where professional antigenpresenting cells are engaged in negative selection. These findings suggest that thymoma generates autoreactive T cells causing autoimmunity. Further investigation on immunological function of thymoma is supposed to elucidate the pathogenesis of thymoma-related autoimmunity and the high affinity of thymoma with myasthenia gravis. In addition, studying the biology of thymoma is also expected to contribute to further understanding of T-cell development and immunological tolerance in the human, because thymoma can be considered an acquired thymus. This review was submitted at the invitation of the editorial committee.     

Thymectomy in the treatment of ocular myasthenia gravis

BACKGROUND: Thymectomy is an effective and accepted treatment for myasthenia gravis, but thymectomy for ocular myasthenia gravis (Osserman stage I) is controversial. OBJECTIVE: To assess the efficacy and propriety of thymectomy for the treatment of ocular myasthenia gravis. METHODS: We conducted a review and follow-up of all patients who had thymectomy for the treatment of ocular myasthenia gravis between 1970 and 1998 at the University of California, Davis, Medical Center, and the University of Rome, "La Sapienza," Rome, Italy. Patient response to thymectomy was categorized as follows: cured, patients who became symptom-free and required no further medication; improved, patients who required less medication and whose symptoms were less severe; unchanged, patients whose symptoms and medications were the same; worse, patients who had more severe symptoms, needed more medication, or died. RESULTS: Sixty-one patients (mean age 37 years; range 14-73 years) were followed up for a mean duration of 9 years (range 0.5-29 years). Ocular myasthenia gravis with mixed and cortical thymomas, stages I to IV, occurred in 12 patients, and ocular myasthenia without thymomas occurred in 49 patients. Transsternal thymectomy (n = 55) and transcervical thymectomy (n = 6) resulted in cure in 31 (51%) patients, improvement in 12 (20%) patients, no change in 16 (26%) patients, and worsening of symptoms (including 1 postoperative death) in 2 patients. Patient outcomes were statistically independent of the duration of preoperative symptoms (mean 9.5 months), patient age, or the presence or absence of thymoma. In patients with ocular myasthenia, 70% were cured or improved after thymectomy; in the subgroup of patients with ocular myasthenia and thymoma, 67% were cured or improved. CONCLUSION: Thymectomy is an effective and safe treatment for patients with ocular myasthenia gravis.     

Thymoma: a ten year review

The histopathology, clinical features, treatment, and results are reported in twenty-nine patients with thymoma. Benign and malignant thymomas are differentiated by their invasive characteristics. Surgical excision is recommended for benign lesions. Surgical excision and postoperative irradiation are recommended for malignant thymomas irrespective of the predominant cell type. The recommended treatment for thymoma and the symptomatic results in myasthenia gravis are unpredictable.     

Multimodality Treatment of Thymoma: A Prospective Study

Background. Thymomas are a heterogeneous group of tumors. Treatment of invasive lesions is not well standardized. The aim of this study is to propose a clinicopathologically based protocol for multimodality therapy.

Methods. Between 1965 and 1988, we operated on 83 patients with thymoma who did not receive standardized adjuvant therapy. In 1989, on the basis of the retrospective analysis of the data, we started a multimodality therapy protocol and used it for 65 patients. Twelve patients had medullary thymoma (11 stage I and 1 stage II), 13 had mixed type (6 stage I and 7 stage II), and 40 had cortical thymoma (4 stage I, 11 stage II, 12 stage III, and 13 stage IV). We considered three groups. Group I (n = 18 patients), benign thymoma, included stage I and II medullary and stage I mixed thymomas; radical resection with no adjuvant therapy was performed. Group II (n = 22), invasive thymoma, included stage I and II cortical and stage II mixed thymomas; postoperative chemotherapy plus radiotherapy was always administered. Group III (n = 25), malignant thymoma, comprised stage III and IV cortical thymomas and stage III mixed thymomas; resectable stage III lesions were removed, and highly invasive stage III and stage IV lesions underwent biopsy, neoadjuvant chemotherapy, and surgical resection; postoperative chemotherapy and radiotherapy was administered to all patients.

Results. The 8-year survival rate for patients in stages I, II, III, and IV was 95%, 100%, 92%, and 68%, respectively. Patients with medullary thymoma had a 92% 8-year survival rate; those with mixed type, 100%; and those with cortical thymoma, 85%. Group I had an 8-year survival rate of 94%; group II, 100%; and group III, 76%. Survival was compared with that of patients operated on before 1989: differences were not significant for group I; survival improved in group II (100% versus 81%; p = not significant); and group III showed significant improvement (76% versus 43%; p < 0.049).

Conclusions. Multimodality treatment with neoadjuvant chemotherapy and adjuvant chemotherapy plus radiotherapy may improve the results of radical resection and the survival of patients with invasive and malignant thymoma.     

Multimodality treatment outcome of invasive thymomas

The aim of the study was to analyze the progression of invasive thymomas associated with myasthenia gravis, after the resection and the progression of unresectable invasive thymomas with a combined chemoradiotherapy. The study was performed on two groups of patients: 8 patients with invasive thymomas and myasthenia gravis operated at the 3rd Surgical Clinic between 1986-1999; 4 patients with unresectable invasive thymomas treated at the Radiology-Oncology Clinic by combined chemoradiotherapy, between 1993-1998. The results are presented for each group of patients, separately. CONCLUSION: The best treatment of invasive thymomas is the multimodal one. The timing of each method was established based on the collaboration between surgeons, medical oncologists, radiotherapists and neurologists, depending on the characteristics of each patient.     

Flow cytometric study of lymphocytes associated with thymoma and other thymic tumors

BACKGROUND. A large number of immature T lymphocytes in thymoma may reflect the biological function of the neoplastic epithelial cells. However, to confirm that this lymphocyte-inducing activity is unique to thymoma, lymphocytes associated with other thymic tumors need to be studied. MATERIALS AND METHODS. We used flow cytometry to study lymphocytes recovered from various thymic tumors (65 thymomas, 24 with myasthenia gravis; 5 thymic cancers; 5 germ cell tumors including 3 needle biopsy samples; and 2 other tumors) and results were analyzed in reference to those from 36 normal thymuses. RESULTS. The frequency of CD4(+)CD8(+) (DP) thymocytes in the normal thymus declined with age (0.9-94%, r = -0.83, P < 0.001) reflecting the physiological involution. Association of lymphocytes with this DP phenotype was unique to thymoma: 61 of 65 thymomas but none of the other thymic tumors had more than 3% DP cells (frequency of DP cells; thymoma without MG, 59.5 +/- 31.4%; thymoma with MG, 59.4 +/- 22.1%; and other thymic tumors, 0.8 +/- 1.0; mean +/- SD). All the thymic tumors associated with myasthenia gravis were thymomas and had more than 18% DP cells. CONCLUSION. The presence of DP cells in thymomas but not in other tumors suggests that DP cells are induced by the epithelial cells of thymoma. This characteristic may help diagnose thymic tumors; the presence of more than 3% DP cells suggests a thymoma. Also, association of myasthenia gravis suggests a thymoma.     

Thymoma is associated with relapse of symptoms after transsternal thymectomy for myasthenia gravis

Thymectomy is considered a therapeutic option for patients with myasthenia gravis. A myasthenic patient who has not received any treatment for years and shows no signs or symptoms of the disease after operation is still susceptible to a recurrence of myasthenic symptoms. To investigate which factors are related to relapse of symptoms in patients having thymectomy, we conduct a retrospective review in the patients who had experienced complete remission after thymectomy. Complete remission was achieved in 92 of 154 patients who received extended transsternal thymectomy for myasthenia gravis. Among these 92 patients, 20 patients had relapse of symptoms and needed medication again after complete remission was achieved (21.7%). Ten of 22 patients in the thymomatous group had relapse of symptom after complete remission was achieved, while only 10 of 70 patients in the nonthymomatous group had relapse of symptom (P=0.006). Multivariate Cox regression analysis revealed that thymoma was an independent factor for the development of relapse of symptoms. In conclusion, thymoma is an adverse prognostic factor for the MG patients who have experienced complete remission after thymectomy. The patients with thymoma had a greater possibility to develop relapse of symptoms than the patients without thymoma.     

Surgical treatment for myasthenia gravis.

A new surgical technique for thymectomy is presented. Three hundred and seventeen patients with myasthenia gravis and 20 with thymomas who had myasthenic symptoms were operated on. The new surgical approach--a small transverse sternotomy--was used in 257 cases (in 240 patients with myasthenia gravis and 17 with thymomas) and conventional median sternotomy in 80. In myasthenic patients small transverse sternotomy enabled radical thymectomy to be performed with an uneventful postoperative course and very good cosmetic results. There were no hospital deaths among patients with myasthenia gravis after thymectomy. The long term results, assessed after 18-24 months, were good: the total remission rate was 39.5%, and there was a great improvement in 48.5% and an improvement in 9%. After thymectomy about 30% of patients received supplementary treatment with prednisone. A correlation between the duration of symptoms and the result of thymectomy was established: the shorter the duration of myasthenia gravis the better the results. In the small group of 20 patients with thymomas two died in hospital. In 12 patients with encapsulated thymic tumours the long term results were similar to those in patients with myasthenia gravis, whereas in patients with infiltrating thymic tumours the results were unsatisfactory.     

Surgical treatment of thymoma.

OBJECTIVE: To describe experience with the surgical treatment of thymoma. DESIGN: A retrospective study. Setting: A teaching hospital at the University of Ottawa. PATIENTS: Over 25 years, 42 consecutive patients (22 men, 20 women) who had a thymoma requiring operation. INTERVENTIONS: Thymectomy. OUTCOME MEASURES: Age, sex, association with myasthenia gravis, presence of a paraneoplastic syndrome, extent of surgical resection, tumour size, histologic features of the tumour, clinical staging of the thymoma and short- and long-term outcome after surgery. RESULTS: The mean (and standard deviation) age of the patients was 52.8 (12.5) years. Thirteen patients had myasthenia gravis. With respect to tumour staging, 24 patients had stage I, 7 had stage II and 11 had stage III disease. Three patients were lost to follow-up. Radiotherapy was used as an adjunct to surgical treatment in 83% of patients with stages II and III disease. Fifty-one percent of patients available for follow-up survived 175.1 months, and the cumulative 5- and 10-year overall survival rates were 87.3% and 81.4% respectively. Only 1 patient died of metastatic thymoma. Complete or partial remission of myasthenia gravis was seen in 10 (77%) affected patients. Mixed cellular histologic features and a tumour size of less than 115 cm3 were more commonly seen with stage I disease. CONCLUSIONS: Thymomas are characterized by slow growth and prolonged survival even in patients with invasive disease as long as the tumour is resected completely and treatment is accompanied by radiotherapy.     

胸腺瘤与胸腺瘤合并重症肌无力的临床探讨

目的　探讨胸腺瘤 (TT)及胸腺瘤合并重症肌无力 (TTMG)的临床特点。方法　对 2 2年间外科治疗的TT 2 5 8例 ,其中单纯TT 16 8例 (组 1) ,TTMG 90例 (组 2 )的临床特点进行对比分析。结果　组 1平均年龄 38 4岁 ,93 4%的病人肿瘤直径大于 5cm ,病理分期多为III、IV期 (6 1 2 % )。组 2平均年龄 46 2岁 ,肿瘤直径 5cm以下占 6 5 6 % ,5 5 2 %为病理I期。结论　早期胸腺瘤诊断标准为 :肿瘤直径<3cm和病理分期I期 ;TTMG的特征是肌无力 (MG)的症状重、病史短、症状进展快、胸腺危象的发生率高。     

Does surgical debulking for advanced stages of thymoma improve survival?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Does surgical debulking for advanced stages of thymoma improve survival?' Altogether, only 17 papers were found using the reported search, of which only 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated; these studies have mainly reported the survival and recurrence rates after total vs subtotal resection of thymic tumours in patients receiving or not receiving adjuvant chemoradiotherapy. These studies confirmed that complete resection is the best prognostic factor in thymomas. With regard to subtotal tumour resection/debulking, we did not find any randomized controlled trials. The evidence on this topic is scarce and these 10 reported were retrospective reviews of the operative, histology and survival data of patients with thymoma who had subtotal vs partial resection for advanced stages of thymoma. Although debulking surgery for thymoma had positively affected survival, in six studies, the difference failed to reach statistical significance. Three of the studies, on the other hand, showed a higher survival rate in thymomas in which maximum debulking was performed and the treatment was followed by high-dose irradiation. None of these studies showed any benefit in debulking surgery for thymic carcinoma. Besides histology and tumour cell-type, other factors influencing survival included the tumour stage and the presence of symptoms such as myasthenia gravis as a warning sign at an early stage. Current evidence in the literature on the survival after debulking surgery for thymoma is contradictory, and most of the studies do not show any survival benefit after debulking for thymoma. However, debulking surgery minimizes the tumour size and area for irradiation postoperatively, hence it can result in less damage to the adjacent tissue during radiotherapy and may be considered for patients in advanced stages of thymoma in whom extensive radiotherapy will be required. In these cases, however, the risks of surgery followed by radiotherapy or radiotherapy alone should carefully be assessed prior to the initiation of treatment.     

Myasthenia Gravis

Treatment of patients with acquired (autoimmune) myasthenia gravis should rely on evidence-based therapeutic choices, taking into account the individual’s needs according to disease severity (mild to severe), extent (ocular or generalized), comorbidities (including other autoimmune diseases, infections, thymoma, and pregnancy), age, iatrogenic factors (the risks and benefits of therapy), patient autonomy and quality of life, financial burden to the patient, and associated health care costs. Therapy is aimed at managing symptoms by improving neuromuscular junction transmission (cholinesterase inhibitors) and/or modifying the underlying immunopathogenetic cause of acquired myasthenia gravis via immunosuppression or immunomodulation. Myasthenic patients with operable thymoma should be referred for surgery and closely followed up for tumor recurrence. A concerted international effort is addressing treatment recommendations for thymectomy in myasthenic patients with no radiologic evidence of thymoma who are positive for circulating acetylcholine receptor antibodies. There is a lack of evidence-based treatment guidelines for both acute and long-term management of ocular myasthenia. Acute management of myasthenic crisis requires intensive monitoring of the patient and institution of an efficient and safe treatment such as plasma exchange. Patient education is essential to a comprehensive long-term treatment plan.     

Clinical and pathologic predictors of outcome in thymoma-associated myasthenia gravis

BACKGROUND: Myasthenia gravis is by far the most common paraneoplastic syndrome of thymomas. There is little information regarding the influence of clinical variables and thymoma-associated factors on biologic development of myasthenia gravis. The aim of the study was to determine independent predictors of clinical outcome in thymoma with myasthenia gravis. METHODS: We studied 108 patients with thymoma-associated myasthenia gravis undergoing removal of the mediastinal mass between 1967 and 2000. Clinical and pathologic variables associated with clinical outcome of myasthenia were assessed by multivariate Cox regression analysis. RESULTS: Patients were followed for a mean period of 10 years (9 months to 33 years). A total of 38 patients died (35.2%), in 14 cases (37%) because of myasthenia gravis and in 6 (16%) because of recurrence of thymoma. With respect to clinical outcome of myasthenia gravis, at the end of the follow-up period, the rate of remission was 16% (n = 17). Of the 91 patients in whom remission was not achieved, 55 had no symptoms with immunosuppressive medication and 36 had symptoms with medication. CONCLUSIONS: In patients with thymoma-associated myasthenia gravis, well-differentiated thymic carcinoma (Müller-Hermelink system), age more than 55 years, and interval from the onset of symptoms to thymectomy of less than 1 year were found to be independent predictors of nonremission of myasthenia gravis after thymectomy.