†Departments of Orthopedics (T. A. D. and C. M.), Pathology (Y. Y.), and Radiology (L. H.), State University of New York Upstate Medical University at Syracuse, 550 Harrison Street, Suite 100, Syracuse, New York 13202. E-mail address for T. A. Damron: email@example.com.
‡Central New York Oncology Associates, 1000 East Genesee, Syracuse, New York 13210.
Metastases to soft tissue from any source are rare, with carcinomas being the most common primary lesion8,9. Metastases from osteosarcomas most commonly are observed in the lungs or bone and rarely are observed elsewhere in the absence of widely disseminated disease10. We present the case of a patient with a distal femoral osteosarcoma who, at the time of diagnosis, had an isolated metastasis to the soft tissue of the chest wall. The purpose of this report is to emphasize the need to consider metastatic disease as a possible explanation for any soft-tissue mass that is discovered at the time of diagnosis, or during treatment, of osteosarcoma.
A thirty-six-year-old man came to us with a two-month history of pain and swelling in the right knee. The patient had been taking ibuprofen to relieve the pain, which initially had been a mild, constant ache involving both the knee and the distal part of the anterior aspect of the thigh. The pain was exacerbated by activity. The patient also noticed mild swelling in the anterior aspect of the thigh. The pain worsened acutely two weeks prior to presentation, when the patient landed on the right leg while playing basketball. Since that time, the pain had begun to awaken him at night and had not been relieved by over-the-counter medications.
During the same two-month period, the patient had a firm, painless lump in the left axillary region; the lump had increased slightly in size. He also reported that swelling had been present in the popliteal region of the contralateral knee for approximately two years. He reported no fevers, chills, or night sweats and had noted no decrease in energy level or appetite.
Upon referral to his local orthopaedic surgeon, the patient was evaluated with radiographs of the right knee, a magnetic resonance imaging study of the right knee, and a total-body bone scan. The left axillary mass was evaluated with an incisional biopsy in the office.
The medical history was unremarkable. A review of the family history revealed that the patient's brother had undergone excision of three benign cysts from the axillary region, leading the patient to believe that his own axillary lesion was also a benign cyst.
On physical examination, the distal part of the right thigh was slightly swollen and warm but was nonerythematous and minimally tender. The circumference of the right thigh was approximately one centimeter larger than that of the left thigh in the immediate suprapatellar region but tapered back to normal at a point approximately ten centimeters proximal to the superior pole of the patella. The swelling of the distal part of the right thigh was most noticeable anteriorly and laterally and appeared to be associated with a mass in the femoral metaphysis. The active range of motion of the right knee was from full extension to 140 degrees of flexion. No instability or effusion in the knee was found. The left knee was normal except for a posteromedial cystic swelling, two centimeters in diameter, that was consistent with a Baker cyst. Just distal to the left axilla, in line with the anterior axillary fold, a fresh transverse three-centimeter scar was seen directly over a subcutaneous soft-tissue mass. The mass was firm and slightly warm, and it measured three centimeters in diameter. Examination of the skin and the lymph nodes did not reveal any café-au-lait spots or adenopathy. Neurovascular examination of both the upper and the lower extremities revealed no abnormalities.
Radiographs showed a sclerotic lesion in the right distal femoral metaphysis (Fig. 1-A and Fig. 1-B). Magnetic resonance images showed that the lesion extended to the soft tissues anteriorly and laterally and into the epiphysis distally (Fig. 2). A technetium-99m bone scan showed increased uptake in the right distal femoral metaphysis as well as in the soft tissue of the left lateral part of the chest wall, just distal to the axilla (Fig. 3). Magnetic resonance images of the chest wall, made after the biopsy, showed a heterogeneous mass (Fig. 4-A and Fig. 4-B). Subsequent radiographs and computerized tomographic scans of the chest revealed normal findings except for the subcutaneous mass in the left part of the chest wall. There was no evidence of mineralization of the mass in the chest wall on any study. A magnetic resonance image of the left knee showed only a small Baker cyst.
A core-needle biopsy of the mass in the distal part of the right femur was performed. Both the soft-tissue lesion of the left part of the chest wall, which had previously undergone a biopsy, and the le-sion in the distal part of the right femur showed the typical histological features of high-grade (grade III of IV) osteosarcoma (Fig. 5-A and Fig. 5-B). The neoplastic cells were osteoblast-like, spindle-shaped, or highly pleomorphic. The osteoblast-like cells exhibited an increased nuclear-to-cytoplasmic ratio as well as eccentric and hyperchromatic nuclei with prominent nucleoli. Mitotic figures with atypical forms were seen frequently. Lace-like osteoid associated with malignant cells was present, representing tumoral matrix pro-duction. Small scattered foci of chondroid differentiation (composed of atypical chondrocytes with chondroid matrix) and fibroblastic differentiation (composed of highly atypical spindle cells) were also identified in both specimens. No associated lymphoid tissue that would otherwise suggest lymph-node involvement was evident in the soft-tissue lesion of the chest wall.
The patient received neoadjuvant multiagent chemotherapy, including two cycles of ifosfamide (3.5 grams per square meter of skin for five days), mesna, and etoposide (100 milligrams per square meter of skin for five days), followed by one cycle of high-dose methotrexate for two consecutive weeks and then by cisplatin and Adriamycin (doxorubicin) on an outpatient basis. Following the first cycle of chemotherapy, Staphylococcus aureus cellulitis developed around the incision in the left part of the chest wall and around the Infuse-a-port (Horizon Medical Products, Manchester, Georgia) (an indwelling venous catheter with a subcutaneous access port). Following a ten-day course of intravenous administration of vancomycin, the soft-tissue mass in the chest wall, which had become more swollen with the associated infection, decreased to a size of three by two centimeters. The mass continued to shrink for the remainder of this course of chemotherapy (Fig. 6-A and Fig. 6-B).
Fourteen weeks after the diagnosis was made, the patient underwent a wide intra-articular resection of the mass in the distal part of the right femur and a wide resection of the mass in the chest wall, both of which resulted in negative margins. The distal part of the femur was reconstructed with a prosthesis. The chest-wall wound was closed primarily. Histological examination of the two specimens showed 99 percent necrosis of the tumor at both sites.
The patient completed chemotherapy according to the Pediatric Oncology Group protocol (number 9450). He remained disease-free until twenty-four months after the resection (twenty-eight months after the diagnosis), at which time he was found to have metastatic pulmonary disease. Four months later, he was alive with disease and was receiving salvage chemotherapy.
The case of our patient, who had metastasis of osteosarcoma to soft tissue at the time of the initial diagnosis of the primary lesion, appears to be unique in the literature. While it has been estimated that as many as 80 percent of patients with osteosarcoma have circulating micrometastases at the time of presentation, only 20 percent have demonstrable metastases at the time of diagnosis (no numbers reported)10. The most frequent sites of clinically or radiographically identified metastasis of osteosarcoma are the lungs and bones, in diminishing order of frequency10. Metastasis of osteosarcoma to other sites rarely is seen in the absence of disseminated disease. However, autopsy studies have revealed cases of metastasis to the regional lymph nodes, kidney, liver, brain, skin, and heart10.
We are aware of two other reports in which a positive radionuclide scan was used to diagnose soft-tissue metastasis in a patient with osteosarcoma1,4. In 1974, Flowers reported the case of a patient in whom a primary osteosarcoma metastasized to the soft tissue of the proximal part of the left thigh in the presence of pulmonary metastases4. The soft-tissue metastasis was heavily mineralized, and a technetium-99m bone scan showed moderate uptake. In 1990, Arrington et al. reported a case in which metastases to the lungs, brain, and two soft-tissue sites (the proximal part of the right arm and the left calf) were diagnosed with use of a technetium-99m bone scan one year after the patient had been managed with amputation and chemotherapy for the treatment of osteosarcoma1. The soft-tissue metastases were clinically unsuspected. Magnetic resonance imaging of the calf confirmed the presence of an intramuscular mass1. Tissue was not obtained for confirmation in either report1,4. The value of nuclear scintigraphy to localize soft-tissue metastases of osteosarcoma was previously documented in a rat model11.
Soft-tissue osteosarcoma occurs much more often as a primary lesion than as a metastatic lesion3. Given the simultaneous presentation of the two lesions in our patient and the equal duration of symptoms at each site, we considered the possibility that the patient had a primary soft-tissue osteosarcoma with bone metastasis to the distal part of the femur. However, we considered the distal femoral bone lesion to be the primary site because of its more typical location and its much larger size. The soft-tissue nodule, which we believed to be a metastatic deposit, was atypical of a primary soft-tissue osteosarcoma because of its subcutaneous location and lack of characteristic peripheral mineralization3.
Other sarcomas that have been reported to metastasize to soft tissue include chondrosarcoma, synovial sarcoma, and angiosarcoma2,5-7. The occurrence of soft-tissue metastasis from any musculoskeletal sarcoma therefore appears to be extremely rare. However, given the demonstrated plausibility of its occurrence, metastasis should be considered during the evaluation of any soft-tissue mass in a patient with primary sarcomatous disease. Any such soft-tissue mass in a patient with known or suspected osteosarcoma should be approached as potentially resectable disease.
The case of our patient is unique in that a solitary soft-tissue metastasis was present at the time of diagnosis of the primary osteosarcoma, there were no other sites of metastatic disease, and the soft-tissue metastasis was confirmed on both magnetic resonance imaging and histological studies. Very little in the way of treatment recommendations can be drawn from this single case. However, the current case is instructive in that the response to chemotherapy was similar at both the metastatic soft-tissue site and the primary site. Although our patient had metastatic disease at the two-year follow-up examination, we favor standard neoadjuvant multiagent chemotherapy and wide surgical resection of both the primary and the metastatic lesion when this situation is encountered.
Note: The authors thank Brett Greenky, M.D., and Shehandrah Haghir, M.D., for their contributions during the preparation of this manuscript.
Investigation performed at the Departments of Orthopedics, Pathology, and Radiology, State University of New York Upstate Medical University, Syracuse
*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.
1. Arrington, E. R.; Eisenberg, B.; Orrison, W. W., Jr. ; and Williamson, M. R.: Scintigraphic appearance of uncommon soft-tissue osteogenic sarcoma metastases. J. Nucl. Med.
, 31: 679-681, 1990.
2. Bansal, R.; Pai, R. R.; Nayak, R.; and Raghuveer, C. V.: Metastatic chondrosarcoma in soft tissue diagnosed by fine needle aspiration (FNA) cytology. Cytopathology
, 7: 70-72, 1996.
3. Enzinger, F. M., and Weiss, S. W.: Soft-tissue osteosarcoma. In Soft Tissue Tumors, edited by F. M. Enzinger and S. W. Weiss. Ed. 3. St. Louis, C. V. Mosby, 1995
4. Flowers, W. M., Jr.: 99MTc-polyphosphate uptake within pulmonary and soft-tissue metastases from osteosarcoma. Radiology
, 112: 377-378, 1974.
5. Hattrup, S. J.; Amadio, P. C.; Sim, F. H.; ; and Lombardi, R. M.: Metastatic tumors of the foot and ankle. Foot and Ankle
, 8: 243-247, 1988.
6. Kohr, R. M.: Primary cardiac angiosarcoma with disseminated bone and soft tissue metastases. A reassessment of diagnostic criteria based upon a review of the literature. Indiana Med.
, 80: 20-23, 1987.
7. Meyer, C. A.; Kransdorf, M. J.; Moser, R. P., Jr.; and Jelinek, J. S.: Case report 716. Soft-tissue metastasis in synovial sarcoma. Skel. Radiol.
, 21: 128-131, 1992.
8. Schultz, S. R.; Bree, R. L.; Schwab, R. E.; and Raiss, G.: CT detection of skeletal muscle metastases. J. Comput. Assist. Tomog.
, 10: 81-83, 1986.
9. Sridhar, K. S.; Rao, R. K.; and Kunhardt, B.: Skeletal muscle metastases from lung cancer. Cancer
, 59: 1530-1534, 1987.
10. Weis, L.: Common malignant bone tumors: osteosarcoma. In Surgery for Bone and Soft-Tissue Tumors, pp. 265-274. Edited by M. A. Simon and D. Springfield. Philadelphia, Lippincott-Raven, 1998
Copyright 2000 by The Journal of Bone and Joint Surgery, Incorporated
11. Woodbury, D. H., , and Beierwaltes, W. H.:: Fluorine-18 uptake and localization in soft tissue deposits of osteogenic sarcoma in rat and man. J. Nucl. Med.,
, 8: 646-651, 1967.