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Thymoma: A Continuing Survey at the Massachusetts General Hospital
Thymoma: A Continuing Suwey at the Massachusetts General Hospital Earle W. Wilkins, Jr., M.D., a n d Benjamin Castleman, M.D. ABSTRACT An analysis is presented of the treatment of 103 patients with thymoma, 56 with myasthenia gravis and 47 without. In a 1966 report on the first 63 patients, it was stated that the presence of myasthenia and the finding of local tumor invasion at operation were ominous prognostic indicators. The augmented series suggests that myasthenia no longer carries this stigma, possibly because of improved methods in its management in patients who have undergone operation.
In 1966, a report of the management of 63 patients with thymoma was presented from the Massachusetts General Hospital [6]. It represented the total experience with such patients from October, 1939, through December, 1963. Thirty-seven of the patients had myasthenia gravis and 26 did not. The two principal factors leading to adverse results were local invasion of the tumor and the presence of myasthenia gravis. The present study was designed to test the validity of the conclusions drawn in that study and to assess results of improved management of patients with thymoma, particularly those with myasthenia gravis. To assist in the specification of invasion, the method of surgicalpathological staging defined by Bergh and collaborators [l] was adapted, with minor modifications, as follows: Stage I: Intact capsule or growth within the capsule Stage 11: Pericapsular growth into the mediastinal fat tissue or adjacent pleura or pericardium From the Departments of Surgery and Pathology, Harvard Medical School, and the Thoracic Surgical Unit, Surgical Services, and Department of Pathology, Massachusetts General Hospital, Boston, MA. Presented at the Fifteenth Annual Meeting of The Society of Thoracic Surgeons, Jan 15-17, 1979, Phoenix, AZ. Address reprint requests to Dr. Wilkins, Massachusetts General Hospital, Boston, MA 02114.
Stage 111: Invasive growth into the surrounding organs, intrathoracic metastases, or both All 40 patients with thymoma diagnosed at the Massachusetts General Hospital from January, 1964, through December, 1977, are included in this study. Pathological slides from the 40 new patients were reviewed by one of us (B. C.). Of the 40 patients, 18 had myasthenia and 22 did not. The total experience reported here consists of 103 patients with thymoma. Myasthenia developed in 1 patient in the original series subsequent to the 1966 report. Therefore, the breakdown in the overall series is 56 patients with myasthenia gravis and 47 without it. During the same time, 16 patients with cysts of the thymus were seen. The 54% incidence of myasthenia gravis in patients with thymoma is higher than in other series [l, 2, 51 and is due, in large measure, to the number of patients with myasthenia seen in the Myasthenia Gravis Clinic, established at the Massachusetts General Hospital in 1935. Follow-up has been complete on all 103 patients through December 31,1978, or until time of death. As in the original paper, the groups with and without myasthenia are considered independently.
Thymoma without Myasthenia Gravis There were 22 patients in this group.from 1964 through 1977. Thirteen were female patients ranging from 15 to 81 years old. The 9 male patients ranged from 13 to 75 years old. SYMPTOMS. In 8 of these patients, the tumor was initially detected on a chest roentgenogram; none had symptoms related to the tumor. In the remaining 14 patients, the presenting symptom was chest pain in 6, cough and fever in 3, weakness and fatigue in 3, and hoarseness and dyspnea in 1 each. One woman, 81 years old, had pancytopenia associated with a spin-
252 0003-4975/79/090252-05$01.25 @ 1978 by Earle W. Wilkins, Jr.
253
Wilkins and Castleman: Thymoma
dle cell thymoma. Two women had pernicious anemia prior to development of the thymoma. In 1 of them, it occurred 12 years following subtotal gastrectomy for carcinoma. Two patients reported herpes zoster within the year prior to diagnosis of thymoma. TREATMENT. Surgical exploration was carried out in 21 patients. In the 81-year-old woman, the diagnosis was established by a percutaneous Vim-Silverman needle biopsy. Total excision was possible in 17 patients, a resectability rate of 81%; biopsy only was carried out in 4. There were 2 operative deaths, occurring as cardiopulmonary arrests in patients with unresectable thymomas. Surgical-pathological staging revealed that there were 13 patients with Stage I disease, 4 with Stage 11, and 4 with Stage I11 disease. Radiation therapy was provided postoperatively in 1 patient in Stage 11 and 2 unresected patients in Stage 111. One of the latter is free from symptoms 2 years after treatment. RESULTS. Three of the Stage I11 patients died; 2 were surgical deaths and 1 died of persistent thymoma. Four other patients, 65 to 81 years old, died of unrelated causes. Ten of 13 patients in Stage I and all 4 patients in Stage I1 are alive. Cumulative survival, calculated by the life-table method [41, for this group of 22 patients is 68% at 5 years.
moma was possible in 17 patients, a resectability rate of 94%. There were no hospital deaths. Surgical and pathological staging revealed that there were 9 patients with Stage I disease, 7 with Stage 11, and 2 with Stage 111. The patient in whom biopsy only was possible was a Stage I11 patient. In the other Stage I11 patient, excision of pleural metastases was accomplished in addition to the mediastinal dissection. Radiation therapy was utilized in 11 patients, 3 preoperatively and 8 postoperatively. Only 1 of the patients in Stage I1 and Stage I11 did not receive irradiation after resection. This was the youngest patient, a 13-yearold girl. Preoperative irradiation is no longer advised in patients with thymoma and myasthenia gravis. RESULTS. Only 1 in this group of 18 patients is dead, a Stage I1 patient who died a year after thymectomy of complications of myasthenia. All others are alive and well up to 13 years after operation. Cumulative survival for this group at 5 years is 94%. Classification of changes in the myasthenia is reported according to the method of Osserman [3]: A (no symptoms, no medication), 3 patients; B (improved but on a regimen of Mestinon [pyridostigmine bromide]), 9; C (unimproved), 5; and D (worse), 1 patient.
Comment In comparing the early results of the recent seThymoma with Myasthenia Gravis ries with those reported in 1966, one distinct There were 18 patients in this group from 1964 change becomes clear. It can no longer be stated through 1977. Seven were female patients, that myasthenia gravis per se ”diminishes the ranging from 13 to 75 years old. The 11 men prospect for long-time survival” [6]. Indeed, the ranged in age from 26 to 61 years old. combination of myasthenia gravis and invasion SYMPTOMS. In 16 patients, the symptoms of of adjacent structures by the thymoma is not “ulmyasthenia led to the diagnosis of thymoma. In timately a lethal combination” [6]. In the small the other 2, the anterior mediastinal mass was groups analyzed from 1964 through 1977, there discovered on routine chest roentgenogram, the actually is a better 5-year cumulative survival myasthenia developing 3 and 12 months after for patients with myasthenia gravis (94%) than operative removal of the thymoma. In 3 of the in those without (68%). The numbers involved 16 patients seen with myasthenia, the thymoma are not sufficiently large to be statistically sigwas not detected until operation. Only 1patient nificant. had an associated hematological disorder, areBetter postoperative supportive care of pagenerative anemia. tients with myasthenia plus improved longTREATMENT. Median sternotomy, permit- term medicinal management of the vicissitudes ting total thymectomy and mediastinal dissec- of myasthenia gravis seem to be the essential tion, was the preferred operative approach in factors in the improved survival. All postthis group of patients. Total removal of thy- operative care in these patients is provided in
254
The Annals of Thoracic Surgery Vol 28 No 3 September 1979
Table I. Cumulative Survivals
Table 2 . Hospital Mortality Survival
Variable
No. of Patients
Total patients 103 Resected tumors 79 Encapsulated 66 tumors Invasive tumors 37 56 My asthenia No myasthenia 47 Encapsulated 28 (no myasthenia) Invasive 18 (myasthenia)
5-Year
10-Year
1
(%)
64 77 75
54 68 67
55
40
57 73
43 67
92
86
46
20
the respiratory intensive care unit. Nasotracheal intubation is coupled with withdrawal of all cholinergic medications for three to five days. Tracheostomy is necessary only in patients requiring respiratory ventilator assistance beyond ten days. This regimen has virtually eliminated hospital postoperative mortality. In the long-term management of myasthenia, the use of high-dose steroids has been particularly effective. Immune globulin has been administered to 2 patients with myasthenia who underwent thymectomy and required prolonged episodes of respiratory support. Plasmapheresis has not been employed in this series. To provide more significant numbers, the cumulative survival [4] for the entire series of 103 patients at the Massachusetts General Hospital was compiled, in relation to a number of variables: resectability, the presence of myasthenia, and invasive character of the thymoma (Table 1). Hospital mortality has shown a progressive decrease (Table 2 ) . All 5 deaths in the first two decades resulted from complications related to cholinergic medication. All occurred before 1954. The 2 more recent deaths occurred in Stage I11 patients with extensive, unresectable thymomas but no myasthenia. The response of patients with thymoma to radiation therapy has been such that these 2 patients might perhaps
Time Span
No. of Operations
No. of Deaths
Percent
1940-49 1950-59 1960-69 1970-1977
17 33 25 28
2 3 1 1
11.8 9.1 4.0 3.6
Total
103
7
6.8
have been more appropriately treated with primary irradiation. There has been no sex differential in the overall series, either in the group with myasthenia (28 male and 28 female patients) or the group without myasthenia (22 male and 25 female patients). Similarly, there has been no difference in survival in either group in relation to sex.
Conclusions 1. Improved methods of postoperative and long-term medicinal management of patients with thymoma and myasthenia gravis seem to have eliminated the presence of myasthenia as an adverse factor affecting survival. 2 . The invasive character of a thymoma continues to be an adverse factor in long-term survival. Local invasion is normally an indication for postoperative irradiation. 3. The 10-year cumulative survival of patients in whom total excision of the thymoma is possible is 68%. References 1. Bergh NP, Gatzinsky P, Larsson S, et al: Tumors
2.
3. 4.
5. 6.
of the thymus and thymic region: I. Clinicopathological studies on thymomas. Ann Thorac Surg 25:91, 1978 Bernatz PE, Khousari S, Harrison EG, et al: Thymoma: factors influencing prognosis. Surg Clin North Am 53:885, 1973 Osserman KE: Myasthenia Gravis. New York, Grune and Stratton, 1958 Puffer RR: Practical statistics in health and medical work. New York, McGraw-Hill, 1950, p p 162166 Weissberg D, Goldberg M, Pearson FG: Thymoma. Ann Thorac Surg 16:141, 1973 Wilkins EW Jr, Edmunds LH Jr, Castleman B:
255 Wilkins and Castleman: Thymoma
Cases of thymoma at Massachusetts General Hospital. J Thorac Cardiovasc Surg 59:322, 1966
younger than the patients without myasthenia gravis. Thus, they would have been expected to have an even better long-term survival. Discussion I would like to ask Dr. Wilkins two questions. DR. PETER c. PAIROLERO (Rochester, MN): I would like First, did you analyze long-term survival in your first to congratulate the Massachusetts General Hospital group of patients for both variables simultaneously? group on this excellent study and to show both the The reason that associated myasthenia gravis did not similarities and dissimilarities of our experience at adversely affect survival could be that the current the Mayo Clinic. Recently we were able to evaluate group of patients have not survived long enough. 197 patients who underwent operation for thymoma Second, is there any prognosticating value of hisand who were followed for more than 25 years. Sur- tological cell typing? vival was analyzed as it related to gross invasion of DR.DOV WEISSBERG (Be’er Yaakov, Israel): Six years the tumor, to the predominant histological cell type, ago in Houston I presented to this Society my experiand to associated myasthenia gravis. ence with 35 patients with thymoma. A unique We agree entirely with Dr. Wilkins that a poor finding was the very high incidence of transpleural prognosis is associated with gross invasion. Overall, seeding of metastases: 40% in patients with invasive 17% of our patients were alive 25 years after thymomas. Like Dr. Wilkins, we reached the concluthymectomy. However, if the thymoma was noninsion that the two most important prognostic factors vasive, survival increased to 23%, whereas if the are encapsulation versus invasion, and myasthenia tumor was invasive, only 9% survived 17 years. gravis. Myasthenia was present in 15 of our patients. As Dr. Wilkins indicated, the predominent type of Patients with noninvasive tumors but no myasthenia cell in the thymoma does not influence survival comgravis had an excellent prognosis; in patients with pared with the invasiveness of the tumor. Irrespecinvasive tumors but no myasthenia, the prognosis tive of the cell type, approximately 65% of our pawas still fair if the tumor was resected. Myasthenia tients survived 10 years if the tumor was noninvasive affected the prognosis adversely in patients with compared with only 30% if the tumor was invasive. both invasive and noninvasive tumors. In patients However, there are differences in the incidence of who had both diseases, myasthenia was a far greater invasiveness associated with the various cell types. threat to the patients than thymoma. I am using purSpindle cell thymomas were less frequently invaposely the term inuasiue rather than malignant besive than epithelial thymomas, and therefore were cause malignancy in thymoma is determined by its associated with a much better prognosis. Approxiinvasiveness rather than by morphology. mately 60% of patients with spindle cell thymoma A very important point in Dr. Wilkins’s presentawere alive 15 years after operation, whereas no pation is development of myasthenia after thymectients with epithelial cell thymoma were alive at 15 tomy. In our series, remission of myasthenia ocyears. curred in 6 patients, but in 4, myasthenia appeared Contrary to Dr. Wilkins’s current report, our exfirst after the operation. Hence, it is very important perience demonstrates that associated myasthenia that the thymectomy be complete. gravis does influence long-term survival-adversely. In recent years there has been an increasing tenOf patients with thymoma but without myasthenia dency to do a thymectomy through the neck. This gravis, 41% were alive 25 years after thymectomy, approach is certainly less traumatic than the standard whereas only 21% with myasthenia gravis were sternotomy. Although recently I started to use this alive. However, when both myasthenia gravis and approach and although at operation the cervical inciinvasiveness were analyzed simultaneously, the sion seems adequate, I am not sure that it always is. most significant determinant of survival was invaFoci of extracapsular thymic tissue may be present in siveness. That is, associated myasthenia gravis did the lower mediastinum and not be reachable through not alter survival if the tumor was already invasive. the neck incision. Therefore, a combination of transIn those patients with invasive thymomas, only 9% sternal and neck incisions might sometimes be necwithout myasthenia gravis survived 15 years comessary, particularly in patients with myasthenia pared with 10% with myasthenia gravis. However, if gravis. the tumor was noninvasive, associated myasthenia gravis did significantly lower survival at each time DR. WILKINS: I appreciate the comments of Dr. Pairolinterval. In those patients with noninvasive thy- ero and Dr. Weissberg. They represent the two inmomas without myasthenia gravis, 61% survived stitutions, Mayo and Toronto General, that I quoted 25 years, whereas if the noninvasive thymoma had in my text. Actually, I think our conclusions about associated myasthenia gravis, only 24% were alive at thymoma are very close. 25 years. This decrease in survival occurred even In answer to Dr. Pairolero’s two questions, in our though the patients with both noninvasive thymoma early series the combination of myasthenia gravis and myasthenia gravis were, on average, 14 years and invasive thymoma did show a 0 to 10% survi-
256 The Annals of Thoracic Surgery
Vol 28 No 3 September 1979
Val. I think perhaps I may be guilty of undue optimism in believing that myasthenia gravis is no longer a major deterrent to long-term survival, but, at least in the limited time that has passed since the newer series has taken place, our figures show that myasthenia gravis, largely due to the good care provided by our neurologists and respiratory care specialists, is no longer an adverse sign. The prognostic value of the histology of the tumor, according to Dr. Castleman, is zero, and as a surgeon I would concur with that. Histology alone does not indicate what survival is likely to be.
Dr. Weissberg has commented on the 40% incidence of pleural implants in his series, and I have done a good bit of corresponding with Griff Pearson about this. It was not mentioned in our review, but the incidence of pleural implants in our overall series is 12%. These patients would be categorized in Stage 111.
Although it is still necessary to watch for what may happen in the long run to patients with myasthenia gravis, I stick by my conclusion that now the major deterrent to long-term survival is local invasion by the tumor.
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In 1966, a report of the management of 63 patients with thymoma was presented from the Massachusetts General Hospital [6]. It represented the total experience with such patients from October, 1939, through December, 1963. Thirty-seven of the patients had myasthenia gravis and 26 did not. The two principal factors leading to adverse results were local invasion of the tumor and the presence of myasthenia gravis. The present study was designed to test the validity of the conclusions drawn in that study and to assess results of improved management of patients with thymoma, particularly those with myasthenia gravis. To assist in the specification of invasion, the method of surgicalpathological staging defined by Bergh and collaborators [l] was adapted, with minor modifications, as follows: Stage I: Intact capsule or growth within the capsule Stage 11: Pericapsular growth into the mediastinal fat tissue or adjacent pleura or pericardium From the Departments of Surgery and Pathology, Harvard Medical School, and the Thoracic Surgical Unit, Surgical Services, and Department of Pathology, Massachusetts General Hospital, Boston, MA. Presented at the Fifteenth Annual Meeting of The Society of Thoracic Surgeons, Jan 15-17, 1979, Phoenix, AZ. Address reprint requests to Dr. Wilkins, Massachusetts General Hospital, Boston, MA 02114.
Stage 111: Invasive growth into the surrounding organs, intrathoracic metastases, or both All 40 patients with thymoma diagnosed at the Massachusetts General Hospital from January, 1964, through December, 1977, are included in this study. Pathological slides from the 40 new patients were reviewed by one of us (B. C.). Of the 40 patients, 18 had myasthenia and 22 did not. The total experience reported here consists of 103 patients with thymoma. Myasthenia developed in 1 patient in the original series subsequent to the 1966 report. Therefore, the breakdown in the overall series is 56 patients with myasthenia gravis and 47 without it. During the same time, 16 patients with cysts of the thymus were seen. The 54% incidence of myasthenia gravis in patients with thymoma is higher than in other series [l, 2, 51 and is due, in large measure, to the number of patients with myasthenia seen in the Myasthenia Gravis Clinic, established at the Massachusetts General Hospital in 1935. Follow-up has been complete on all 103 patients through December 31,1978, or until time of death. As in the original paper, the groups with and without myasthenia are considered independently.
Thymoma without Myasthenia Gravis There were 22 patients in this group.from 1964 through 1977. Thirteen were female patients ranging from 15 to 81 years old. The 9 male patients ranged from 13 to 75 years old. SYMPTOMS. In 8 of these patients, the tumor was initially detected on a chest roentgenogram; none had symptoms related to the tumor. In the remaining 14 patients, the presenting symptom was chest pain in 6, cough and fever in 3, weakness and fatigue in 3, and hoarseness and dyspnea in 1 each. One woman, 81 years old, had pancytopenia associated with a spin-
252 0003-4975/79/090252-05$01.25 @ 1978 by Earle W. Wilkins, Jr.
253
Wilkins and Castleman: Thymoma
dle cell thymoma. Two women had pernicious anemia prior to development of the thymoma. In 1 of them, it occurred 12 years following subtotal gastrectomy for carcinoma. Two patients reported herpes zoster within the year prior to diagnosis of thymoma. TREATMENT. Surgical exploration was carried out in 21 patients. In the 81-year-old woman, the diagnosis was established by a percutaneous Vim-Silverman needle biopsy. Total excision was possible in 17 patients, a resectability rate of 81%; biopsy only was carried out in 4. There were 2 operative deaths, occurring as cardiopulmonary arrests in patients with unresectable thymomas. Surgical-pathological staging revealed that there were 13 patients with Stage I disease, 4 with Stage 11, and 4 with Stage I11 disease. Radiation therapy was provided postoperatively in 1 patient in Stage 11 and 2 unresected patients in Stage 111. One of the latter is free from symptoms 2 years after treatment. RESULTS. Three of the Stage I11 patients died; 2 were surgical deaths and 1 died of persistent thymoma. Four other patients, 65 to 81 years old, died of unrelated causes. Ten of 13 patients in Stage I and all 4 patients in Stage I1 are alive. Cumulative survival, calculated by the life-table method [41, for this group of 22 patients is 68% at 5 years.
moma was possible in 17 patients, a resectability rate of 94%. There were no hospital deaths. Surgical and pathological staging revealed that there were 9 patients with Stage I disease, 7 with Stage 11, and 2 with Stage 111. The patient in whom biopsy only was possible was a Stage I11 patient. In the other Stage I11 patient, excision of pleural metastases was accomplished in addition to the mediastinal dissection. Radiation therapy was utilized in 11 patients, 3 preoperatively and 8 postoperatively. Only 1 of the patients in Stage I1 and Stage I11 did not receive irradiation after resection. This was the youngest patient, a 13-yearold girl. Preoperative irradiation is no longer advised in patients with thymoma and myasthenia gravis. RESULTS. Only 1 in this group of 18 patients is dead, a Stage I1 patient who died a year after thymectomy of complications of myasthenia. All others are alive and well up to 13 years after operation. Cumulative survival for this group at 5 years is 94%. Classification of changes in the myasthenia is reported according to the method of Osserman [3]: A (no symptoms, no medication), 3 patients; B (improved but on a regimen of Mestinon [pyridostigmine bromide]), 9; C (unimproved), 5; and D (worse), 1 patient.
Comment In comparing the early results of the recent seThymoma with Myasthenia Gravis ries with those reported in 1966, one distinct There were 18 patients in this group from 1964 change becomes clear. It can no longer be stated through 1977. Seven were female patients, that myasthenia gravis per se ”diminishes the ranging from 13 to 75 years old. The 11 men prospect for long-time survival” [6]. Indeed, the ranged in age from 26 to 61 years old. combination of myasthenia gravis and invasion SYMPTOMS. In 16 patients, the symptoms of of adjacent structures by the thymoma is not “ulmyasthenia led to the diagnosis of thymoma. In timately a lethal combination” [6]. In the small the other 2, the anterior mediastinal mass was groups analyzed from 1964 through 1977, there discovered on routine chest roentgenogram, the actually is a better 5-year cumulative survival myasthenia developing 3 and 12 months after for patients with myasthenia gravis (94%) than operative removal of the thymoma. In 3 of the in those without (68%). The numbers involved 16 patients seen with myasthenia, the thymoma are not sufficiently large to be statistically sigwas not detected until operation. Only 1patient nificant. had an associated hematological disorder, areBetter postoperative supportive care of pagenerative anemia. tients with myasthenia plus improved longTREATMENT. Median sternotomy, permit- term medicinal management of the vicissitudes ting total thymectomy and mediastinal dissec- of myasthenia gravis seem to be the essential tion, was the preferred operative approach in factors in the improved survival. All postthis group of patients. Total removal of thy- operative care in these patients is provided in
254
The Annals of Thoracic Surgery Vol 28 No 3 September 1979
Table I. Cumulative Survivals
Table 2 . Hospital Mortality Survival
Variable
No. of Patients
Total patients 103 Resected tumors 79 Encapsulated 66 tumors Invasive tumors 37 56 My asthenia No myasthenia 47 Encapsulated 28 (no myasthenia) Invasive 18 (myasthenia)
5-Year
10-Year
1
(%)
64 77 75
54 68 67
55
40
57 73
43 67
92
86
46
20
the respiratory intensive care unit. Nasotracheal intubation is coupled with withdrawal of all cholinergic medications for three to five days. Tracheostomy is necessary only in patients requiring respiratory ventilator assistance beyond ten days. This regimen has virtually eliminated hospital postoperative mortality. In the long-term management of myasthenia, the use of high-dose steroids has been particularly effective. Immune globulin has been administered to 2 patients with myasthenia who underwent thymectomy and required prolonged episodes of respiratory support. Plasmapheresis has not been employed in this series. To provide more significant numbers, the cumulative survival [4] for the entire series of 103 patients at the Massachusetts General Hospital was compiled, in relation to a number of variables: resectability, the presence of myasthenia, and invasive character of the thymoma (Table 1). Hospital mortality has shown a progressive decrease (Table 2 ) . All 5 deaths in the first two decades resulted from complications related to cholinergic medication. All occurred before 1954. The 2 more recent deaths occurred in Stage I11 patients with extensive, unresectable thymomas but no myasthenia. The response of patients with thymoma to radiation therapy has been such that these 2 patients might perhaps
Time Span
No. of Operations
No. of Deaths
Percent
1940-49 1950-59 1960-69 1970-1977
17 33 25 28
2 3 1 1
11.8 9.1 4.0 3.6
Total
103
7
6.8
have been more appropriately treated with primary irradiation. There has been no sex differential in the overall series, either in the group with myasthenia (28 male and 28 female patients) or the group without myasthenia (22 male and 25 female patients). Similarly, there has been no difference in survival in either group in relation to sex.
Conclusions 1. Improved methods of postoperative and long-term medicinal management of patients with thymoma and myasthenia gravis seem to have eliminated the presence of myasthenia as an adverse factor affecting survival. 2 . The invasive character of a thymoma continues to be an adverse factor in long-term survival. Local invasion is normally an indication for postoperative irradiation. 3. The 10-year cumulative survival of patients in whom total excision of the thymoma is possible is 68%. References 1. Bergh NP, Gatzinsky P, Larsson S, et al: Tumors
2.
3. 4.
5. 6.
of the thymus and thymic region: I. Clinicopathological studies on thymomas. Ann Thorac Surg 25:91, 1978 Bernatz PE, Khousari S, Harrison EG, et al: Thymoma: factors influencing prognosis. Surg Clin North Am 53:885, 1973 Osserman KE: Myasthenia Gravis. New York, Grune and Stratton, 1958 Puffer RR: Practical statistics in health and medical work. New York, McGraw-Hill, 1950, p p 162166 Weissberg D, Goldberg M, Pearson FG: Thymoma. Ann Thorac Surg 16:141, 1973 Wilkins EW Jr, Edmunds LH Jr, Castleman B:
255 Wilkins and Castleman: Thymoma
Cases of thymoma at Massachusetts General Hospital. J Thorac Cardiovasc Surg 59:322, 1966
younger than the patients without myasthenia gravis. Thus, they would have been expected to have an even better long-term survival. Discussion I would like to ask Dr. Wilkins two questions. DR. PETER c. PAIROLERO (Rochester, MN): I would like First, did you analyze long-term survival in your first to congratulate the Massachusetts General Hospital group of patients for both variables simultaneously? group on this excellent study and to show both the The reason that associated myasthenia gravis did not similarities and dissimilarities of our experience at adversely affect survival could be that the current the Mayo Clinic. Recently we were able to evaluate group of patients have not survived long enough. 197 patients who underwent operation for thymoma Second, is there any prognosticating value of hisand who were followed for more than 25 years. Sur- tological cell typing? vival was analyzed as it related to gross invasion of DR.DOV WEISSBERG (Be’er Yaakov, Israel): Six years the tumor, to the predominant histological cell type, ago in Houston I presented to this Society my experiand to associated myasthenia gravis. ence with 35 patients with thymoma. A unique We agree entirely with Dr. Wilkins that a poor finding was the very high incidence of transpleural prognosis is associated with gross invasion. Overall, seeding of metastases: 40% in patients with invasive 17% of our patients were alive 25 years after thymomas. Like Dr. Wilkins, we reached the concluthymectomy. However, if the thymoma was noninsion that the two most important prognostic factors vasive, survival increased to 23%, whereas if the are encapsulation versus invasion, and myasthenia tumor was invasive, only 9% survived 17 years. gravis. Myasthenia was present in 15 of our patients. As Dr. Wilkins indicated, the predominent type of Patients with noninvasive tumors but no myasthenia cell in the thymoma does not influence survival comgravis had an excellent prognosis; in patients with pared with the invasiveness of the tumor. Irrespecinvasive tumors but no myasthenia, the prognosis tive of the cell type, approximately 65% of our pawas still fair if the tumor was resected. Myasthenia tients survived 10 years if the tumor was noninvasive affected the prognosis adversely in patients with compared with only 30% if the tumor was invasive. both invasive and noninvasive tumors. In patients However, there are differences in the incidence of who had both diseases, myasthenia was a far greater invasiveness associated with the various cell types. threat to the patients than thymoma. I am using purSpindle cell thymomas were less frequently invaposely the term inuasiue rather than malignant besive than epithelial thymomas, and therefore were cause malignancy in thymoma is determined by its associated with a much better prognosis. Approxiinvasiveness rather than by morphology. mately 60% of patients with spindle cell thymoma A very important point in Dr. Wilkins’s presentawere alive 15 years after operation, whereas no pation is development of myasthenia after thymectients with epithelial cell thymoma were alive at 15 tomy. In our series, remission of myasthenia ocyears. curred in 6 patients, but in 4, myasthenia appeared Contrary to Dr. Wilkins’s current report, our exfirst after the operation. Hence, it is very important perience demonstrates that associated myasthenia that the thymectomy be complete. gravis does influence long-term survival-adversely. In recent years there has been an increasing tenOf patients with thymoma but without myasthenia dency to do a thymectomy through the neck. This gravis, 41% were alive 25 years after thymectomy, approach is certainly less traumatic than the standard whereas only 21% with myasthenia gravis were sternotomy. Although recently I started to use this alive. However, when both myasthenia gravis and approach and although at operation the cervical inciinvasiveness were analyzed simultaneously, the sion seems adequate, I am not sure that it always is. most significant determinant of survival was invaFoci of extracapsular thymic tissue may be present in siveness. That is, associated myasthenia gravis did the lower mediastinum and not be reachable through not alter survival if the tumor was already invasive. the neck incision. Therefore, a combination of transIn those patients with invasive thymomas, only 9% sternal and neck incisions might sometimes be necwithout myasthenia gravis survived 15 years comessary, particularly in patients with myasthenia pared with 10% with myasthenia gravis. However, if gravis. the tumor was noninvasive, associated myasthenia gravis did significantly lower survival at each time DR. WILKINS: I appreciate the comments of Dr. Pairolinterval. In those patients with noninvasive thy- ero and Dr. Weissberg. They represent the two inmomas without myasthenia gravis, 61% survived stitutions, Mayo and Toronto General, that I quoted 25 years, whereas if the noninvasive thymoma had in my text. Actually, I think our conclusions about associated myasthenia gravis, only 24% were alive at thymoma are very close. 25 years. This decrease in survival occurred even In answer to Dr. Pairolero’s two questions, in our though the patients with both noninvasive thymoma early series the combination of myasthenia gravis and myasthenia gravis were, on average, 14 years and invasive thymoma did show a 0 to 10% survi-
256 The Annals of Thoracic Surgery
Vol 28 No 3 September 1979
Val. I think perhaps I may be guilty of undue optimism in believing that myasthenia gravis is no longer a major deterrent to long-term survival, but, at least in the limited time that has passed since the newer series has taken place, our figures show that myasthenia gravis, largely due to the good care provided by our neurologists and respiratory care specialists, is no longer an adverse sign. The prognostic value of the histology of the tumor, according to Dr. Castleman, is zero, and as a surgeon I would concur with that. Histology alone does not indicate what survival is likely to be.
Dr. Weissberg has commented on the 40% incidence of pleural implants in his series, and I have done a good bit of corresponding with Griff Pearson about this. It was not mentioned in our review, but the incidence of pleural implants in our overall series is 12%. These patients would be categorized in Stage 111.
Although it is still necessary to watch for what may happen in the long run to patients with myasthenia gravis, I stick by my conclusion that now the major deterrent to long-term survival is local invasion by the tumor.
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