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Benign giant cell tumor of femur with bilateral multiple pulmonary metastases
Benign giant cell tumor of femur with bilateral multiple pulmonary metastases This paper presents the unusual case of a patient with a histologically benign giant cell tumor of the femur that resulted in bilateral multiple pulmonary metastases having the appearance of benign giant cell tumor. An aggressive surgical approach was used to eradicate the pulmonary metastases; 25 nodules excised from the left lung and 33 nodules from the right lung were proved histologically to be benign giant cell tumors. Three years after bilateral thoracotomies, he remains well, without evidence of recurrent disease, and his lung function is almost normal.
Hiroshi Inoue, M.D.,* Tsuneo Ishihara, M.D.,* Takaaki Ikeda, M.D.,* and Atsuo Mikata, M.D.,** Tokyo, Japan
T
he clinical behavior of giant cell tumor of the bone cannot be predicted by its microscopic appearance. 1, 2 On very rare occasions a giant cell. tumor which appears to be benign on histologic study may even metastisize to distant sites without its histologic patterns changing. The following report is of a case of a histologically benign giant cell tumor of the right femur in a patient who subsequently had multiple bilateral pulmonary metastases. The pattern of the metastases was identical to that of the tissue resected from the femur. The pulmonary lesions were resected.
Case report A 31-year-old man, who was first seen at Toden Hospital on July, 1969, at the age of 24 years, had had pain in the right knee for about 6 months. Roentgenographic examination showed changes characteristic of a giant cell tumor of the distal end of the femur (Fig. I). A chest roentgenogram showed no abnormalities at this time. At operation in July, 1969, the lesion was proved by immediate frozen-section examination to be a giant cell tumor. It was removed by curettage and the defect was packed with homologous bone chips. Postoperative radiation was not given. The patient was discharged and remained well after operation. On March 23, 1971, 20 months after the first operation, a routine follow-up roentgenogram revealed a recurrent lesion in the distal end of the right femur (Fig. 2), and a chest roentgenogram showed a nodular density in the left midlung field (Fig. 3). From the Departments of Surgery and Pathology, School of Medicine, Keio University, Tokyo, Japan. Received for publication March I, 1977. Accepted for publication April 26, 1977. *Department of Surgery. **Department of Pathology.
Fig. 1. An osteolytic expanding lesion at the distal end of the right femur. He was readmitted on April 20, 1971. The recurrent tumor was managed by wide resection of the distal portion of the femur, and the knee joint was reconstructed with a hinged prosthesis. Microscopic examination of the tumor showed a well-differentiated giant cell tumor composed of loose oval stromal cells with slight pleomorphism and numerous multinucleated giant cells (Fig. 4). Convalescence of the knee joint was satisfactory and no definite therapy was applied to the pulmonary lesion. He was asymptomatic and in good general health except for several transitory bouts of mild cough. On May 2, 1973, a follow-up chest roentgenogram showed that the nodular density in the lung had grown and another nodule had appeared in the right lower lung field (Fig. 5). On Jan. 24, 1974, the patient was referred to the Keio
935
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93 6 Inoue et al.
Thoracic and Cardiovascular Surgery
Fig. 4. Microscopic section shows the appearance of the benign giant cell tumor. (Hematoxylin and eosin. Original magnification x 200 .) Fig. 2. Recurrent giant cell tumor of the femur.
Fig. 5. Chest roentgenogram on May 2, 1973. Another nodule in the right lower lung field.
Fig. 3. Chest roentgenogram on March 23. 1971. There is a metastatic lesion in the left midlung field . Univer sity Hospital for surgical treatment of the pulmonary lesion s. Whole chest tomograms on admission revealed multiple nodules in both lungs, at least five in the left lung and three in the right lung. Results of laboratory studies remained within normal limits . On Feb . 4, 1974, a left thoracotomy was performed and 30 nodules, the diameters of which ranged from a few millimeters to 2 em. , were found within
the substance of the left lung . Each nodule , along with a thin layer of the surrounding normal lung tissue , was excised . By pathological examination 25 nodules out of the 30 resected proved to be metastases of the histologically benign giant cell tumor of the bone. They were identical to the lesion removed from the femur . On March 6, 1974, a right thoracotomy was done and 39 nodules were found within the right lung. All of them were resected, and 33 nodules were pathologically diagnosed as metastases of the benign giant cell tumor of the bone (F ig. 6). The postoperative cour se was uneventful, and the patient was discharged on March 31, 1974. At present , 8 years after the onset of the original tumor, 5 years after the appearance of known pulmonary metastases,
Volume 74
Benign giant cell tumor offemur
Number 6 December, 1977
Fig. 6. Microscopic section of the tumors within the lung parenchyma shows the appearance of a benign giant cell tumor of the bone. (Hematoxylin and eosin. Original magnification x 200.) and about 3 years after the thoracotomies, the patient remains well with slight lameness in right leg. Roentgenographic examination in December, 1976, showed no evidence of recurrent diseases in either the chest or the femur (Fig. 7).
Fig. 7. Chest roentgenogram on Dec. 14, 1976. Table I. Results of lung function tests before and after the operations Two weeks Before after left operation thoracotomy (1/28/74) (2/19/74)
Comment
Giant cell tumor of the bone can metastasize by way of two different types of growth. A frankly malignant change may occur in the stroma cells of the primary tumor; alternatively, ~he tumor may metastasize without histologic changes in its cells. Confirmation of the former can be found in many published reports. This type is exemplified by the case reported by Finch and Gleave;" in which the metastasis had a malignant appearance. On the other hand, examples of the latter are quite rare. Orr" published a case of giant cell tumor of the lower femur with pulmonary metastases, although the pulmonary metastases alone are described. This case is likely to be the first published example of a pulmonary metastasis having the appearance of a histologically benign giant cell tumor. Since then, approximately eleven acceptable examples have been reported." !' The explanation for metastasis from a giant cell tumor is based upon the fact that tumor thrombi are frequently observed in vascular spaces in a giant cell tumor. Some tumor thrombi do become detached and carried to other sites, where on rare occasions they may establish themselves as autologous transplants. Even if histologically benign, pulmonary metastases of the giant cell tumor should be resected thoroughly because they can grow. In our case pulmonary metastases were
9 37
VC (%VC) MVV (%MVV) FEVl.O (FEVl.O%)
3.40 (85) 128.9 (103) 3.27 (83)
2.34 (59) 83.3 (68) 1.99 (81)
Three weeks after right thoracotomy (3/25/74)
Two years after the thoracotomies (6/3/76)
1.52 (38) 95.9 (81) 1.52 (83)
3.00 (75) 107 (88) 2.43 (79)
Legend: ve, Vital capacity. MVV, Maximal voluntary ventilation. FEV ... , Forced expiratory volume in 1 second.
bilateral and numerous. They were resected by the method of Ishihara." All visible and palpable nodules in the lung were initially marked by 2-0 nylon, and then each nodule, along with a thin covering of normal lung tissue, was resected. By this method, diffusely located metastases could be removed with minimal deficit in lung function. Table I shows the results of lung function tests of this patient before and after operation. Seven weeks after the left thoracotomy and 3 weeks after the right thoracotomy, the vital capacity of this patient was somewhat impaired. However, 2 years after the operations, this loss had been restored to a remarkable degree. The data presented here suggest that an aggressive surgical approach is the desirable treatment for patients with this rare entity.
938
Inoue et al.
REFERENCES
2
3 4
5
6
7
Johnson, E. W., Jr., and Dahlin, D. c.: Treatment of Giant Cell Tumor of Bone, J. Bone Joint Surg. (Arn.) 41: 895, 1959, Goldenberg, R. R., Cambell, C. 1., and Bonfiglio, M.: Giant Cell Tumor of Bone: An Analysis of Two Hundred and Eighteen Cases, J. Bone Joint Surg. (Am.) 52A: 619, 1970. Orr,1. W.: Malignant Osteoclastoma, J. Pathol. 34: 265, 1931. Russell, D. S.: Malignant Osteoclastoma and the Association of Malignant Osteoclastoma With Paget's Osteitis Deformans, J. Bone Joint Surg. 31B: 281, 1949. Haas, A., and Ritter, S. A.: "Benign: Giant Cell Tumor of Femur With Embolic Metastasis in Prepuce of Penis, Am. 1. Surg. 89: 573, 1955. Murphy, W. R., and Ackerman, L. V.: Benign and Malignant Giant Cell Tumors of Bone: A ClinicalPathological Evaluation of Thirty-one Cases, Cancer 9: 317,1956. Pan, P., and Mackinnon, W. B.: "Benign" Giant Cell Tumor of Thoracic Vertebra With Pulmonary Metastasis, Can. Med. Assoc. J. 87: 1026, 1962.
The Journal of Thoracic and Cardiovascular Surgery
8 Jewell, J. H., and Bush, L. F.: "Benign" Giant Cell Tumor of Bone With a Solitary Pulmonary Metastasis, J. Bone Joint Surg. 46: 848, 1964. 9 Pan, P., Dahlin, D. C., Lipscomb, P. R., and Bernatz, P. E.: "Benign" Giant Cell Tumor of the Radius With Pulmonary Metastasis, Mayo Clin. Proc. 39: 344, 1964. 10 Gresen, A. A., Dahlin, D. c., Peterson, L. F. A., and Payne, W. S.: "Benign" Giant Cell Tumor of Bone Metastasizing to Lung, Ann. Thorac. Surg. 16: 531, 1973. II Kutchemeshgi, A. D., Wright, J. R., and Humphrey, R. L.: Pulmonary Metastases From a Well-Differentiated Giant Cell Tumor of Bone: Report of a Patient With Apparent Response to Cyclophosphamide Therapy, Johns Hopkins Med. J. 134: 237, 1974. 12 Finch, E. F., and Gleave, H. H.: A Case of Osteoclastoma (Myeloid Sarcoma, Benign Giant Cell Tumor) With Pulmonary Metastasis, 1. Pathol. 29: 399, 1926. 13 Ishihara, T.: Tenisei Haishuyo (Metastatic Pulmonary Tumors), Jpn. J. Thorac. Surg. 28: 245, 1975.
Hiroshi Inoue, M.D.,* Tsuneo Ishihara, M.D.,* Takaaki Ikeda, M.D.,* and Atsuo Mikata, M.D.,** Tokyo, Japan
T
he clinical behavior of giant cell tumor of the bone cannot be predicted by its microscopic appearance. 1, 2 On very rare occasions a giant cell. tumor which appears to be benign on histologic study may even metastisize to distant sites without its histologic patterns changing. The following report is of a case of a histologically benign giant cell tumor of the right femur in a patient who subsequently had multiple bilateral pulmonary metastases. The pattern of the metastases was identical to that of the tissue resected from the femur. The pulmonary lesions were resected.
Case report A 31-year-old man, who was first seen at Toden Hospital on July, 1969, at the age of 24 years, had had pain in the right knee for about 6 months. Roentgenographic examination showed changes characteristic of a giant cell tumor of the distal end of the femur (Fig. I). A chest roentgenogram showed no abnormalities at this time. At operation in July, 1969, the lesion was proved by immediate frozen-section examination to be a giant cell tumor. It was removed by curettage and the defect was packed with homologous bone chips. Postoperative radiation was not given. The patient was discharged and remained well after operation. On March 23, 1971, 20 months after the first operation, a routine follow-up roentgenogram revealed a recurrent lesion in the distal end of the right femur (Fig. 2), and a chest roentgenogram showed a nodular density in the left midlung field (Fig. 3). From the Departments of Surgery and Pathology, School of Medicine, Keio University, Tokyo, Japan. Received for publication March I, 1977. Accepted for publication April 26, 1977. *Department of Surgery. **Department of Pathology.
Fig. 1. An osteolytic expanding lesion at the distal end of the right femur. He was readmitted on April 20, 1971. The recurrent tumor was managed by wide resection of the distal portion of the femur, and the knee joint was reconstructed with a hinged prosthesis. Microscopic examination of the tumor showed a well-differentiated giant cell tumor composed of loose oval stromal cells with slight pleomorphism and numerous multinucleated giant cells (Fig. 4). Convalescence of the knee joint was satisfactory and no definite therapy was applied to the pulmonary lesion. He was asymptomatic and in good general health except for several transitory bouts of mild cough. On May 2, 1973, a follow-up chest roentgenogram showed that the nodular density in the lung had grown and another nodule had appeared in the right lower lung field (Fig. 5). On Jan. 24, 1974, the patient was referred to the Keio
935
The Journal of
93 6 Inoue et al.
Thoracic and Cardiovascular Surgery
Fig. 4. Microscopic section shows the appearance of the benign giant cell tumor. (Hematoxylin and eosin. Original magnification x 200 .) Fig. 2. Recurrent giant cell tumor of the femur.
Fig. 5. Chest roentgenogram on May 2, 1973. Another nodule in the right lower lung field.
Fig. 3. Chest roentgenogram on March 23. 1971. There is a metastatic lesion in the left midlung field . Univer sity Hospital for surgical treatment of the pulmonary lesion s. Whole chest tomograms on admission revealed multiple nodules in both lungs, at least five in the left lung and three in the right lung. Results of laboratory studies remained within normal limits . On Feb . 4, 1974, a left thoracotomy was performed and 30 nodules, the diameters of which ranged from a few millimeters to 2 em. , were found within
the substance of the left lung . Each nodule , along with a thin layer of the surrounding normal lung tissue , was excised . By pathological examination 25 nodules out of the 30 resected proved to be metastases of the histologically benign giant cell tumor of the bone. They were identical to the lesion removed from the femur . On March 6, 1974, a right thoracotomy was done and 39 nodules were found within the right lung. All of them were resected, and 33 nodules were pathologically diagnosed as metastases of the benign giant cell tumor of the bone (F ig. 6). The postoperative cour se was uneventful, and the patient was discharged on March 31, 1974. At present , 8 years after the onset of the original tumor, 5 years after the appearance of known pulmonary metastases,
Volume 74
Benign giant cell tumor offemur
Number 6 December, 1977
Fig. 6. Microscopic section of the tumors within the lung parenchyma shows the appearance of a benign giant cell tumor of the bone. (Hematoxylin and eosin. Original magnification x 200.) and about 3 years after the thoracotomies, the patient remains well with slight lameness in right leg. Roentgenographic examination in December, 1976, showed no evidence of recurrent diseases in either the chest or the femur (Fig. 7).
Fig. 7. Chest roentgenogram on Dec. 14, 1976. Table I. Results of lung function tests before and after the operations Two weeks Before after left operation thoracotomy (1/28/74) (2/19/74)
Comment
Giant cell tumor of the bone can metastasize by way of two different types of growth. A frankly malignant change may occur in the stroma cells of the primary tumor; alternatively, ~he tumor may metastasize without histologic changes in its cells. Confirmation of the former can be found in many published reports. This type is exemplified by the case reported by Finch and Gleave;" in which the metastasis had a malignant appearance. On the other hand, examples of the latter are quite rare. Orr" published a case of giant cell tumor of the lower femur with pulmonary metastases, although the pulmonary metastases alone are described. This case is likely to be the first published example of a pulmonary metastasis having the appearance of a histologically benign giant cell tumor. Since then, approximately eleven acceptable examples have been reported." !' The explanation for metastasis from a giant cell tumor is based upon the fact that tumor thrombi are frequently observed in vascular spaces in a giant cell tumor. Some tumor thrombi do become detached and carried to other sites, where on rare occasions they may establish themselves as autologous transplants. Even if histologically benign, pulmonary metastases of the giant cell tumor should be resected thoroughly because they can grow. In our case pulmonary metastases were
9 37
VC (%VC) MVV (%MVV) FEVl.O (FEVl.O%)
3.40 (85) 128.9 (103) 3.27 (83)
2.34 (59) 83.3 (68) 1.99 (81)
Three weeks after right thoracotomy (3/25/74)
Two years after the thoracotomies (6/3/76)
1.52 (38) 95.9 (81) 1.52 (83)
3.00 (75) 107 (88) 2.43 (79)
Legend: ve, Vital capacity. MVV, Maximal voluntary ventilation. FEV ... , Forced expiratory volume in 1 second.
bilateral and numerous. They were resected by the method of Ishihara." All visible and palpable nodules in the lung were initially marked by 2-0 nylon, and then each nodule, along with a thin covering of normal lung tissue, was resected. By this method, diffusely located metastases could be removed with minimal deficit in lung function. Table I shows the results of lung function tests of this patient before and after operation. Seven weeks after the left thoracotomy and 3 weeks after the right thoracotomy, the vital capacity of this patient was somewhat impaired. However, 2 years after the operations, this loss had been restored to a remarkable degree. The data presented here suggest that an aggressive surgical approach is the desirable treatment for patients with this rare entity.
938
Inoue et al.
REFERENCES
2
3 4
5
6
7
Johnson, E. W., Jr., and Dahlin, D. c.: Treatment of Giant Cell Tumor of Bone, J. Bone Joint Surg. (Arn.) 41: 895, 1959, Goldenberg, R. R., Cambell, C. 1., and Bonfiglio, M.: Giant Cell Tumor of Bone: An Analysis of Two Hundred and Eighteen Cases, J. Bone Joint Surg. (Am.) 52A: 619, 1970. Orr,1. W.: Malignant Osteoclastoma, J. Pathol. 34: 265, 1931. Russell, D. S.: Malignant Osteoclastoma and the Association of Malignant Osteoclastoma With Paget's Osteitis Deformans, J. Bone Joint Surg. 31B: 281, 1949. Haas, A., and Ritter, S. A.: "Benign: Giant Cell Tumor of Femur With Embolic Metastasis in Prepuce of Penis, Am. 1. Surg. 89: 573, 1955. Murphy, W. R., and Ackerman, L. V.: Benign and Malignant Giant Cell Tumors of Bone: A ClinicalPathological Evaluation of Thirty-one Cases, Cancer 9: 317,1956. Pan, P., and Mackinnon, W. B.: "Benign" Giant Cell Tumor of Thoracic Vertebra With Pulmonary Metastasis, Can. Med. Assoc. J. 87: 1026, 1962.
The Journal of Thoracic and Cardiovascular Surgery
8 Jewell, J. H., and Bush, L. F.: "Benign" Giant Cell Tumor of Bone With a Solitary Pulmonary Metastasis, J. Bone Joint Surg. 46: 848, 1964. 9 Pan, P., Dahlin, D. C., Lipscomb, P. R., and Bernatz, P. E.: "Benign" Giant Cell Tumor of the Radius With Pulmonary Metastasis, Mayo Clin. Proc. 39: 344, 1964. 10 Gresen, A. A., Dahlin, D. c., Peterson, L. F. A., and Payne, W. S.: "Benign" Giant Cell Tumor of Bone Metastasizing to Lung, Ann. Thorac. Surg. 16: 531, 1973. II Kutchemeshgi, A. D., Wright, J. R., and Humphrey, R. L.: Pulmonary Metastases From a Well-Differentiated Giant Cell Tumor of Bone: Report of a Patient With Apparent Response to Cyclophosphamide Therapy, Johns Hopkins Med. J. 134: 237, 1974. 12 Finch, E. F., and Gleave, H. H.: A Case of Osteoclastoma (Myeloid Sarcoma, Benign Giant Cell Tumor) With Pulmonary Metastasis, 1. Pathol. 29: 399, 1926. 13 Ishihara, T.: Tenisei Haishuyo (Metastatic Pulmonary Tumors), Jpn. J. Thorac. Surg. 28: 245, 1975.