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Thymoma
Thymoma JAMES W. KILMAN, KARL P. KLASSEN,
Thymic tumors are the fourth most common tumor encountered in the mediastinum, comprising about 10 per cent of all mediastinal tumors [I$]. Tumors of the thymus are certainly the most common cause of an anterior mediastinal mass found by roentgenogram or physical examination [3]. Multiple methods of classification of thymic tumors have been proposed, but from a practical surgical standpoint, they are best classified as invasive and noninvasive [4]. This classification presents the surgeon with a unique opportunity to predict malignancy or benignity on the basis of gross appearance at the time of surgery and on the ease and completeness of surgical extirpation. This classification of thymic tumors into invasive tumors and noninvasive tumors as originally pointed out by Bernatz, Harrison, and Clagett [5] and Legg and Brady [6] and modified somewhat by Shields, Fox, and Lees [4] has proved to be a reliable method of determining the prognosis concerning the individual tumor. Recent reviews of the surgical management of thymomas have emphasized a more aggressive approach in the management of thymic tumors [7,8]. An aggressive surgical approach to tumors of the thymus has been proposed by one of us (JWK) for several years. This management philosophy has prompted us to review our experience with the surgical management of thymoma at the Ohio State University Hospitals during the past twenty years. Tumors were classified in retrospect as noninvasive if the surgeon was able to resect the tumor completely and easily. If the tumor was thought to be incompletely resected or if contiguous structures were resected with the tumor, it was considered to be invasive. Patient
Material
A thymic tumor was found at surgery in 59 of 112 patients presenting with the clinical impression and x-ray findings of an anterior mediastinal mass. The majority of the patients (forty of the fifty-nine) were in the third, fourth, and fifth decades of life, with the youngest having surgery at one day of age and the oldest at seventy-two years of age. From Ohio
710
the State
Department University
of Surgery. Division of Thoracic Surgery, College of Medicine, Columbus, Ohio 43210.
The
MD Columbus, MD, Columbus,
Ohio Ohio
Females predominated, comprising 63 per cent of the present series. The females also had the disease at a younger age in general than did the twenty-two males in this series. Twenty patients with a thymic tumor were asymptomatic. Seventeen had chest pain and eight patients had a chronic cough. Three patients had the physical findings and symptoms of superior vena caval obstruction, Three had the signs and symptoms of myasthenia gravis. Two patients manifested dysphagia. Two patients complained of hoarseness. Diagnosis and surgical therapy were achieved through a complete or upper median sternotomy in most cases. A right or left thoracotomy was used in a limited number of cases. Surgical extirpation was thought to be complete without involvement of contiguous structures in thirty-eight cases, and these tumors were therefore designated as noninvasive. Limited excision, excision including contiguous structures such as the superior vena cava or biopsy, was performed in twenty-one cases and these tumors were therefore designated as invasive tumors. Eighty-four per cent of the thirty-eight patients with noninvasive tumors are living and well at the time of review, with a mean survival time of 5.1 years. Only 33 per cent of those with invasive tumors are living and well at the time of review, with a mean survival time of only 2.8 years. (Figure 1.) In the patients with granulomatous thymoma, eight of twelve tumors were noted to be noninvasive at surgery and all patients are alive with the exception of one patient who died of acute bacterial endocarditis with no evidence of tumor at autopsy. In this same group four patients were thought to have an invasive thymic tumor at surgery and, therefore, only limited resection was performed. All were treated with x-ray therapy, and all four are alive. Three of the patients with an invasive tumor and one with a noninvasive tumor have manifested a disease similar to true Hodgkin’s disease with distal lymph node involvement. The survival time of this group is three to sixteen years. (Figure 2.) Comments
The therapy of thymic tumors offers the surgeon a unique opportunity at the operating table since he is able to predict the patient’s ultimate prognosis better than can the pathologist by careful microscopic examination and cellular identification. The noninvasive or invasive characteristic is also important in determining the need for adjunctive The
Amerlcrn Journal
of SUrEfew
Thymoma 6
16 I YEARS
MX SURVIVAL IN YEARS
1
4 3
1
ONON-INVASIVE &%INVASIVE Ii NOOGKINSDISEASE
I2 SURVIVAL IN YEARS 0 :
i 2 4 I 1
iL
L
NON-INVASIVE
INVASIVE
Figure 1. Survival statistics in fifty-nine patients with thymic tumors. A mean survival of 5.1 years was achieved with the complete surgical extirpation of a noninvasive tumor.
therapy such as radiation or chemotherapy. An aggressive surgical approach is recommended for all tumors of the thymus. This has produced good results in this series of patients, with an over-all survival rate of 66 per cent. The survival rate of patients whose tumor was completely excised is 84 per cent regardless of the eventual cell type as determined by the pathologist. The data concerning granulomatous thymoma are most remarkable. Much controversy exists concerning this tumor and its basic nature remains obscure. Some pathologists believe this tumor to be a distinctive type of thymic neoplasm [9] whereas others consider it only a cell variant of other types of thymoma [IO]. A final group of investigators regard granulomatous thymoma and Hodgkin’s disease as the same process [11,12]. In four of the twelve patients with granulomatous thymoma in this series, a disease eventually developed which was clinically diagnosed as Hodgkin’s disease, including distant lymph node involvement and identification of Reed-Sternberg cells. The patients with granulomatous thymoma in whom Hodgkin’s disease eventually developed all had a tumor which was identified as invasive at the time of surgery and was incompletely excised. Optimal therapy in this group seems to be complete excision of the tumor and radiation therapy to the mediastinum. All patients have survived tumor therapy and one patient has survived sixteen years after excision of the tumor with no evidence of recurrence. Surgical excision is best performed through a median sternotomy which allows better dissection around the base of the heart and great vessels and extension into the neck if needed. The surgical procedure should include removal of all tumor, fat, and lymph nodes in the area with adjacent pericardium if this is found to be adherent. Involved lung may require resection, and tumor may have to be peeled off the adventitia of the great vessels. We do not advocate x-ray therapy for all patients, but Volume
121, June
1971
Figure 2. Survival statistics of twelve patients with granulomatous thymoma. In the patients marked “H,” Hodgkin’s disease eventually developed involving distal lymphatic tissue proved by surgical biopsy.
believe that those with incomplete resection should have this adjunctive therapy. All patients who have a diagnosis of granulomatous thymoma should have radiation therapy to the mediastinum. Chemotherapy has not seemed to benefit these patients. Summary
An aggressive surgical approach is advocated in tumors of the thymus gland. Complete excision of a thymoma in this series has resulted in a survival rate of 84 per cent regardless of the cell type as identified by the pathologist. The surgeon is able to predict prognosis concerning the individual tumor at the operating table by determining if the tumor is invasive or noninvasive and by the ease and completeness of the surgical excision. Complete surgical excision seems to be the therapy of choice for all thymic tumors. References 1. Boyd DP, Adams i-ID, Gerard FP: Tumors of the thymus. Surg Clin N Amer 41: 667, 1961. 2. Effler DB, McCormack LJ: Thymic neoplasms. J Thorac Surg 31: 60, 1956. 3. Ellis K, Gregg HG: Thymomas: roentgen considerations. Amer J Roentgen 91: 105, 1964. 4. Shields TW, Fox RT, Lees WM: Thymic tumors. Arch Surg 92: 617, 1966. PE. Harrison EG. Clagett OT: Thvmoma: a 5. Bernatz clinico-p&hologic study: J Thorac Cardiovasc Surg 42: 424, 1961. 6. Legg MA, Brady WJ: Pathology and clinical behavior of thymomas: a survey of 51 cases. Cancer 18: 1131, 1965. of thymomas. Ann Thorac 7. Sawyers JL: Management Surg 5: 193, 1968. 8. Sawyers JL, Foster JH: Surgical treatment of thymomas. Arch Surg 96: 814, 1968. 9. Lowenhaupt E, Brown R: Carcinoma of the thymus of granulomatous type. Cancer 4: 1193, 1951. 10. Andritsakis GD, Sommers SC: Criteria of thymic cancer and clinical correlations of thymic tumors. J Thorac Surg 37: 273, 1959. 11. Thomson AD: The thymic origin of Hodgkin’s disease. Brit J Cancer 9: 37, 1955. JA, Fonkalsrud EW, Richards W: Granulo12. Wilkerson matous thymoma in childhood. Dis Chest 54: 76. 1968.
711
Thymic tumors are the fourth most common tumor encountered in the mediastinum, comprising about 10 per cent of all mediastinal tumors [I$]. Tumors of the thymus are certainly the most common cause of an anterior mediastinal mass found by roentgenogram or physical examination [3]. Multiple methods of classification of thymic tumors have been proposed, but from a practical surgical standpoint, they are best classified as invasive and noninvasive [4]. This classification presents the surgeon with a unique opportunity to predict malignancy or benignity on the basis of gross appearance at the time of surgery and on the ease and completeness of surgical extirpation. This classification of thymic tumors into invasive tumors and noninvasive tumors as originally pointed out by Bernatz, Harrison, and Clagett [5] and Legg and Brady [6] and modified somewhat by Shields, Fox, and Lees [4] has proved to be a reliable method of determining the prognosis concerning the individual tumor. Recent reviews of the surgical management of thymomas have emphasized a more aggressive approach in the management of thymic tumors [7,8]. An aggressive surgical approach to tumors of the thymus has been proposed by one of us (JWK) for several years. This management philosophy has prompted us to review our experience with the surgical management of thymoma at the Ohio State University Hospitals during the past twenty years. Tumors were classified in retrospect as noninvasive if the surgeon was able to resect the tumor completely and easily. If the tumor was thought to be incompletely resected or if contiguous structures were resected with the tumor, it was considered to be invasive. Patient
Material
A thymic tumor was found at surgery in 59 of 112 patients presenting with the clinical impression and x-ray findings of an anterior mediastinal mass. The majority of the patients (forty of the fifty-nine) were in the third, fourth, and fifth decades of life, with the youngest having surgery at one day of age and the oldest at seventy-two years of age. From Ohio
710
the State
Department University
of Surgery. Division of Thoracic Surgery, College of Medicine, Columbus, Ohio 43210.
The
MD Columbus, MD, Columbus,
Ohio Ohio
Females predominated, comprising 63 per cent of the present series. The females also had the disease at a younger age in general than did the twenty-two males in this series. Twenty patients with a thymic tumor were asymptomatic. Seventeen had chest pain and eight patients had a chronic cough. Three patients had the physical findings and symptoms of superior vena caval obstruction, Three had the signs and symptoms of myasthenia gravis. Two patients manifested dysphagia. Two patients complained of hoarseness. Diagnosis and surgical therapy were achieved through a complete or upper median sternotomy in most cases. A right or left thoracotomy was used in a limited number of cases. Surgical extirpation was thought to be complete without involvement of contiguous structures in thirty-eight cases, and these tumors were therefore designated as noninvasive. Limited excision, excision including contiguous structures such as the superior vena cava or biopsy, was performed in twenty-one cases and these tumors were therefore designated as invasive tumors. Eighty-four per cent of the thirty-eight patients with noninvasive tumors are living and well at the time of review, with a mean survival time of 5.1 years. Only 33 per cent of those with invasive tumors are living and well at the time of review, with a mean survival time of only 2.8 years. (Figure 1.) In the patients with granulomatous thymoma, eight of twelve tumors were noted to be noninvasive at surgery and all patients are alive with the exception of one patient who died of acute bacterial endocarditis with no evidence of tumor at autopsy. In this same group four patients were thought to have an invasive thymic tumor at surgery and, therefore, only limited resection was performed. All were treated with x-ray therapy, and all four are alive. Three of the patients with an invasive tumor and one with a noninvasive tumor have manifested a disease similar to true Hodgkin’s disease with distal lymph node involvement. The survival time of this group is three to sixteen years. (Figure 2.) Comments
The therapy of thymic tumors offers the surgeon a unique opportunity at the operating table since he is able to predict the patient’s ultimate prognosis better than can the pathologist by careful microscopic examination and cellular identification. The noninvasive or invasive characteristic is also important in determining the need for adjunctive The
Amerlcrn Journal
of SUrEfew
Thymoma 6
16 I YEARS
MX SURVIVAL IN YEARS
1
4 3
1
ONON-INVASIVE &%INVASIVE Ii NOOGKINSDISEASE
I2 SURVIVAL IN YEARS 0 :
i 2 4 I 1
iL
L
NON-INVASIVE
INVASIVE
Figure 1. Survival statistics in fifty-nine patients with thymic tumors. A mean survival of 5.1 years was achieved with the complete surgical extirpation of a noninvasive tumor.
therapy such as radiation or chemotherapy. An aggressive surgical approach is recommended for all tumors of the thymus. This has produced good results in this series of patients, with an over-all survival rate of 66 per cent. The survival rate of patients whose tumor was completely excised is 84 per cent regardless of the eventual cell type as determined by the pathologist. The data concerning granulomatous thymoma are most remarkable. Much controversy exists concerning this tumor and its basic nature remains obscure. Some pathologists believe this tumor to be a distinctive type of thymic neoplasm [9] whereas others consider it only a cell variant of other types of thymoma [IO]. A final group of investigators regard granulomatous thymoma and Hodgkin’s disease as the same process [11,12]. In four of the twelve patients with granulomatous thymoma in this series, a disease eventually developed which was clinically diagnosed as Hodgkin’s disease, including distant lymph node involvement and identification of Reed-Sternberg cells. The patients with granulomatous thymoma in whom Hodgkin’s disease eventually developed all had a tumor which was identified as invasive at the time of surgery and was incompletely excised. Optimal therapy in this group seems to be complete excision of the tumor and radiation therapy to the mediastinum. All patients have survived tumor therapy and one patient has survived sixteen years after excision of the tumor with no evidence of recurrence. Surgical excision is best performed through a median sternotomy which allows better dissection around the base of the heart and great vessels and extension into the neck if needed. The surgical procedure should include removal of all tumor, fat, and lymph nodes in the area with adjacent pericardium if this is found to be adherent. Involved lung may require resection, and tumor may have to be peeled off the adventitia of the great vessels. We do not advocate x-ray therapy for all patients, but Volume
121, June
1971
Figure 2. Survival statistics of twelve patients with granulomatous thymoma. In the patients marked “H,” Hodgkin’s disease eventually developed involving distal lymphatic tissue proved by surgical biopsy.
believe that those with incomplete resection should have this adjunctive therapy. All patients who have a diagnosis of granulomatous thymoma should have radiation therapy to the mediastinum. Chemotherapy has not seemed to benefit these patients. Summary
An aggressive surgical approach is advocated in tumors of the thymus gland. Complete excision of a thymoma in this series has resulted in a survival rate of 84 per cent regardless of the cell type as identified by the pathologist. The surgeon is able to predict prognosis concerning the individual tumor at the operating table by determining if the tumor is invasive or noninvasive and by the ease and completeness of the surgical excision. Complete surgical excision seems to be the therapy of choice for all thymic tumors. References 1. Boyd DP, Adams i-ID, Gerard FP: Tumors of the thymus. Surg Clin N Amer 41: 667, 1961. 2. Effler DB, McCormack LJ: Thymic neoplasms. J Thorac Surg 31: 60, 1956. 3. Ellis K, Gregg HG: Thymomas: roentgen considerations. Amer J Roentgen 91: 105, 1964. 4. Shields TW, Fox RT, Lees WM: Thymic tumors. Arch Surg 92: 617, 1966. PE. Harrison EG. Clagett OT: Thvmoma: a 5. Bernatz clinico-p&hologic study: J Thorac Cardiovasc Surg 42: 424, 1961. 6. Legg MA, Brady WJ: Pathology and clinical behavior of thymomas: a survey of 51 cases. Cancer 18: 1131, 1965. of thymomas. Ann Thorac 7. Sawyers JL: Management Surg 5: 193, 1968. 8. Sawyers JL, Foster JH: Surgical treatment of thymomas. Arch Surg 96: 814, 1968. 9. Lowenhaupt E, Brown R: Carcinoma of the thymus of granulomatous type. Cancer 4: 1193, 1951. 10. Andritsakis GD, Sommers SC: Criteria of thymic cancer and clinical correlations of thymic tumors. J Thorac Surg 37: 273, 1959. 11. Thomson AD: The thymic origin of Hodgkin’s disease. Brit J Cancer 9: 37, 1955. JA, Fonkalsrud EW, Richards W: Granulo12. Wilkerson matous thymoma in childhood. Dis Chest 54: 76. 1968.
711