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Japanese Journal of Clinical Oncology Pages 395-398

Osteosarcoma Metastatic to the Kidneys Without Lung Involvement
Introduction
Case report
Discussion
References
Osteosarcoma Metastatic to the Kidneys Without Lung Involvement

Osteosarcoma Metastatic to the Kidneys Without Lung Involvement

Akira Ogose1, Tetsuro Morita1, Iwao Emura2, Keiichi Nemoto3 and Yasuharu Hirata1

Departments of 1Orthopaedic Surgery and 3Pathology, Niigata Cancer Center Hospital, Niigata and 2Department of Pathology, Niigata University School of Medicine, Niigata, Japan

Symptomatic renal metastasis is very rare in osteosarcoma. A few reported cases had pulmonary metastases before renal involvement. We present a case of metastatic renal osteosarcoma without pulmonary involvement. The patient presented with hematuria 8 years after initial treatment of osteosarcoma of the left distal femur. Computed tomography revealed a bilateral calcified renal mass. The patient died of disease 4 months after detection of the metastases. At autopsy, metastatic osteosarcoma was discovered in the bilateral kidney, both renal veins, inferior vena cava and right atrium. There was no pulmonary involvement. We emphasize the need for renal evaluation for the follow-up of patients with osteosarcoma.

Key words: osteosarcoma - kidney metastasis - cardiac metastasis

INTRODUCTION

Although intensive multimodality therapy has prolonged the survival of patients with osteosarcoma, the prognosis of patients with metastatic diseases is still poor. Early detection of the metastases may affect the outcome. In autopsy cases, over 90% have pulmonary metastases and 10-12% have renal metastases (1,2). However, pre-mortem diagnosis of renal metastasis is very rare. Some reports have described such cases and those patients usually had pulmonary metastases before renal involvement (3-11). We describe a case of metastatic osteosarcoma in the kidneys without lung metastasis and present a review of the literature.

CASE REPORT

In April 1986, a 19-year-old female underwent marginal excision of a bone tumor of the left femur at another hospital. The tumor was located on the posterior surface of the distal femur. The pathological diagnosis was osteochondroma. In March 1991, the tumor reoccurred with a large soft tissue nodule and heavily osteoplastic lesion in the medullary cavity and the patient was referred to our hospital (Fig. 1). A biopsy proved parosteal osteosarcoma with intramedullary dedifferentiated element.


Figure 1. Lateral radiograph of the left distal femur, demonstrating a heavily mineralized intramedullary tumor with a large soft tissue nodule.

Histologically, the tumor contained well differentiated osseous trabeculae and spindle to oval tumor cells with minimal atypia (Fig. 2). There were areas of conventional high-grade osteosarcoma in the medullary cavity (dedifferentiation) (Fig. 3). The serum alkaline phosphatase (ALP) level was 428 IU/l (normal, 77-244 IU/l).


Figure 2. Histological section of the parosteal osteosarcoma of the femur. There are well developed bone trabeculae and spindle to oval tumor cells (×180).


Figure 3. Histological section of the conventional osteosarcoma in parosteal osteosarcoma (dedifferentiation). There are irregular bone formation with atypical tumor cells (×360).

Preoperatively, four cycles of chemotherapy with a high dose of methotrexate were performed. Plain radiographs after chemotherapy did not show remarkable changes, but the serum ALP level was decreased to 228 IU/l. The patient underwent wide resection and prosthetic replacement in September, 1991. Histologically, all surgical margins were freed from the tumor. In high-grade tumor (dedifferentiation), over 90% of areas showed tumor necrosis, whereas in low-grade tumor, no tumor necrosis was observed. Two weeks after the surgery, acute renal failure developed, possibly as a result of hemolytic jaundice due to blood transfusion. Hemodialysis was performed for 15 days and her renal function recovered. A further six cycles of adjuvant chemotherapy with doxorubicin were performed. In April 1992, the patient underwent thigh amputation because of late infection of the endoprosthesis. Although routine follow-up chest radiography had revealed no metastatic nodules, the patient presented with a 1-month history of hematuria in November 1993. The serum ALP level was elevated to 764 IU/l. Plain abdominal radiography revealed multiple mineralized nodules in the renal regions (Fig. 4). Computed tomography confirmed a heavily mineralized mass in the bilateral kidneys and tumor thrombus in the inferior vena cava (Fig. 5). A Tc-99m bone scan showed marked uptake in the kidneys without any bone involvement (Fig. 6).


Figure 4. Anteroposterior abdominal radiograph showing multiple mineralized lesions.


Figure 5. Tc-99m bone scan showing multiple areas of increased uptake in the bilateral kidneys.


Figure 6. Abdominal computed tomography showing multiple mineralized nodules in the bilateral kidneys.

The patient continued to deteriorate and died of disease in April 1994. At autopsy, there were an 8 × 13 × 11 cm firm osteosarcoma in the left kidney and numerous small metastatic nodules in the right kidney (Fig. 7). The tumors extended into the bilateral renal veins, inferior vena cava and right atrium. There were no metastatic lesions in other organs including the bilateral lungs.


Figure 7. Histological section of the metastatic osteosarcoma in the kidney. There are urinary tubli on the left side and fine lace-like osteoid with osteosarcoma cells on the right side (×180).

DISCUSSION

Parosteal osteosarcoma often develops at the posterior surface of the distal femur. This low-grade malignant tumor can show features mimicking osteochondroma in both radiographic and histological respects. Incomplete resection is often associated with local recurrence and high-grade change (dedifferentiation) and this dedifferentiation markedly increases the risk of metastasis as conventional osteosarcoma (12). Retrospectively, the clinical course of this case indicates that this tumor was initially a parosteal osteosarcoma and developed dedifferentiation.

The reported incidence of renal metastasis of extrarenal neoplasms varies from 2 to 20% (13). In osteosarcomas, 10-12% of patient autopsies showed renal involvement (1,2). Renal metastasis of osteosarcoma is usually detected after death as part of widespread disease. Pre-mortem diagnosis of renal metastasis is very rare. Jeffree et al. (2) reported no cases of clinical renal metastasis in 91 osteosarcomas. In our series, only one of 110 patients had a pre-mortem diagnosis of renal metastases. Although the true incidence of pre-mortem diagnosis of renal metastasis is unknown, we found 10 such cases, including the present case, in the literature (Table 1) (3-11). There were eight females and two males. The age at diagnosis of metastatic renal tumor ranged from 15 to 27 years (mean, 23 years). Primary tumors were located in seven femurs, one ulna, one tibia and one fibula. Three patients had bilateral kidney metastases, four had left metastases and three had right metastases. The time from treatment of primary tumor to diagnosis of renal metastases was long (4-168 months; mean, 62 months). The reason for the long duration is probably that patients with rapidly progressive osteosarcomas do not usually undergo renal evaluation before their death and only long-term survivors receive renal evaluation. Five patients had no symptoms, three had pain and two had hematuria. Five of eight abdominal radiographies showed calcification and four of four bone scans showed abnormally increased uptake in the kidneys. Even in the patients whose abdominal radiography showed no calcification, bone scans showed abnormality. Advanced osteosarcoma often develops bone metastasis (1). Therefore, bone scan for routine follow-up of patients of osteosarcoma is recommended for the detection of metastases of not only the bone but also the kidney. We consider that patients with advanced osteosarcoma should undergo a bone scan every 6 months.

Table 1. Literature review of metastatic osteosarcoma of the kidney
Authors Age/ gender Primary site Interval to renal metastasis (months) Metastasis of other lesions Symptom Calcification on abdominal radiography Uptake on bone scan Urinalysis Prognosis
Marshall and Drake (3) 33/f R. femur 128 Lung Pain + UK Hematuria Alive at least 20 months
Nelson et al. (4) 23/m L. femur 4 Lung None + UK Normal DOD 4 months
Watson and Cubilla (5) 15/f R. femur 30 Lung Flank pain - UK UK UK
Goldstein et al. (6) 25/f R. femur 36 Lung, bone None + UK Normal DOD 3 months
Hallet et al. (7) 27/f L. ulna 168 Lung None UK + UK Alive at least 24 months
Ayres et al. (8) 16/f L. femur 24 Lung, bone None - + Normal DOD 6 months
Lockhart et al. (9) 17/f R. tibia 29 Lung None - + UK Alive at least 20 months
Barnes et al. (10) 21/m L. fibula 46 Lung Hematuria + UK Hematuria UK
Raby et al. (11) 21/f R. femur 60 Lung Flank pain UK UK UK UK
Present case 27/f L. femur 90 Atrium Hematuria + + Hematuria DOD 6 months
UK, unknown; DOD, dead of disease.

The level of serum ALP is frequently elevated in patients with osteosarcoma and elevation of ALP after surgery indicates, persistent, recurrent or metastatic disease (14). In the present case, ALP was elevated after the renal metastases.

Although the prognosis of these patients was poor, three patients survived at least 20 months after complete removal of the renal tumors. Early detection and complete surgical removal of the renal lesion may provide worthwhile palliation and long-term survival.

All previously reported cases had pulmonary metastases before the detection of renal lesions. However, the present patient had no history of lung metastasis. Autopsy also showed no pulmonary involvement. The reason for the unusual metastatic pattern in this case is not clear. Animal experiments demonstrated that tissue regeneration influenced tumor metastases and the inflammatory reaction promoted tumor metastasis at the site of regenerated tissues (15). Acute renal failure caused by hemolytic jaundice and recovery by hemodialysis in this case may be a reason for this unique metastatic pattern.

In conclusion, osteosarcoma can develop renal metastasis long after initial treatment. For early detection of this unusual metastasis, bone scan is an appropriate routine follow-up examination for patients with osteosarcoma.

References

1. McKenna RJ, Schwinn CP, Soong KY, Higinbotham NL. Sarcoma of the osteogenic series (osteosarcoma, fibrosarcoma, chondrosarcoma, parosteal osteogenic sarcoma and sarcomata arising in abnormal bones). J Bone Joint Surg 1966;48-A:1-26.

2. Jeffree GM, Price CHG, Sisson HA. The metastatic patterns of osteosarcoma. Br J Cancer 1975;32:87-107. MEDLINE Abstract

3. Marshall DM, Drake EH. Transthoracic nephrectomy for metastatic osteogenic sarcoma of the kidney. J Maine Med Assoc 1950;41:320-3.

4. Nelson JA, Clark R, Palubinskas AJ. Osteogenic sarcoma with calcified renal metastasis. Br J Radiol 1971;44:802-4. MEDLINE Abstract

5. Watson RC, Cubilla AL. Osteogenic sarcoma metastatic to the kidney. Clin Bull 1975;5:114-5. MEDLINE Abstract

6. Goldstein C, Ambos MA, Bosniak MA. Multiple ossified metastases to the kidney from osteogenic sarcoma. Am J Roentgenol 1977;128:148-9.

7. Hallet MB, Weiss MA, Aron BS Bracken RB. Secondary renal osteogenic sarcoma 14 years after primary therapy. J Urol 1984;132:752-4. MEDLINE Abstract

8. Ayres R, Curry NS, Gorden L, Bradford BF. Renal metastases from osteogenic sarcoma. Urol Radiol 1985;7:39-41. MEDLINE Abstract

9. Lockhart SK, Coan JD, Jaffe N, Eftekhari F, David C, Shirkhoda A. Osteosarcoma metastatic to the kidney. Clin Imaging 1989;13:154-6. MEDLINE Abstract

10. Barnes DG, Gnanapavan M, McGeorge A. Solitary renal metastasis from osteogenic sarcoma. J R Coll Edinb 1990;35:314.

11. Raby WN, Kopplin P, Weitzman S. Metastatic osteosarcoma of the kidney presenting as renal hemorrhage. J Pediatr Hematol Oncol 1996;18:321-2. MEDLINE Abstract

12. Okada K, Frassica FJ, Sim FH, Beabout JH, Bond JR, Unni KK. Parosteal osteosarcoma: a clinicopathological study. J Bone Joint Surg 1994;76-A:366-78.

13. Choyke PL, White EM, Zeman RK, Jaffe MH, Clark LR. Renal metastases: clinicopathologic and radiologic correlation. Radiology 1987;162:359-63. MEDLINE Abstract

14. Dorfman HD, Czerniak B. Osteosarcoma. In: Dorfman HD, Czerniak B, editors. Bone Tumors. St. Louis: Mosby 1998;128-252.

15. Murthy SM, Goldschmidt RA, Rao LN, Ammirati M, Buchmann T, Scanlon EF. The influence of surgical trauma on experimental metastasis. Cancer 1989;64:2035-44. MEDLINE Abstract

Received April 16, 1999; accepted May 24, 1999
For reprints and all correspondence: Tetsuro Morita, Department of Orthopaedic Surgery, Niigata Cancer Center Hospital, Kawagishicho 2, Niigata 951-8566, Japan

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Last modification: 23 Aug 1999
Copyright© 1999 Foundation for Promotion of Cancer Research.
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