Fig. IA: An AP view of the left knee reveals a mixed lytic and sclerotic process with ill-defined margins and cortical irregularity involving the distal medial metaphysis of the femur.
Fig. IB: The lesion is not well seen on the lateral view.
Fig. 2: Radiographs obtained one month later reveal progression of osteolysis with cortical breakthrough and a large soft tissue component (arrows).
A 21 year old male complained of gradually increasing pain and swelling of the left knee of two months' duration. Radiographs were obtained (Fig. 1); however, the patient refused treatment, only to return one month later with persistent symptoms (Fig. 2). Your diagnosis?
A 21 year old male complained of gradually increasing pain and swelling of the left knee of two months' duration. Radiographs of the left knee revealed a poorly defined, mixed lytic and sclerotic lesion with cortical irregularity involving the distal medial metaphysis of the femur. A malignant process was suspected; however, the patient refused treatment. The patient returned with persistent symptoms one month later, at which time radiographs revealed progression to a "blown-out" pattern with a prominent soft tissue component.
A CT scan of the left lower extremity (Fig. 3) revealed extensive osteolysis with cortical disruption involving the medial femoral condyle and medial metaphyseal region with proximal extension of intramedullary tumor. A small amount of new bone formation or calcific matrix was identified within the intraosseous portion of the lesion. The tumor had a large soft tissue component, evident on plain films and more clearly delineated by CT. Percutaneous needle biopsy was performed with a Craig needle under fluoroscopic guidance, the diagnosis was telangiectatic osteosarcoma. This diagnosis was later confirmed after amputation.
A chest radiograph revealed several small, scattered nodular densities. CT examination of the lungs revealed multiple, bilateral parenchymal and subpleural nodules (about 25), consistent with metastatic disease (Fig. 4). No additional tumor foci were identified on bone scan or liver-spleen scan. The patient was treated with preoperative and postoperative multidrug chemotherapy and above-the-knee amputation. Despite continued chemotherapy, the pulmonary nodules increased tn size and number and spontaneous bilateral pneumomoraces developed, initially without associated symptoms (Fig. 5). A progressive downhill course ended in the patient's demise seven months after initial presentation.
Telangiectatic osteosarcoma was first described by Paget in 1854 as a "medullary cancer of the bone with excessive development of vessels,"1 Later, the term "malignant bone aneurysm" was used to describe the lesion.2 In 1922, Ewing3 considered the lesion a histologic variant of osteogenic sarcoma and it has since been classified as such. Although studies have indicated that patients with telangiectatic osteosarcoma bave a worse prognosis than tiiose with ordinary osteosarcoma,46 a recent study of over one hundred patients demonstrated no difference in survival when comparing patients with telangiectatic osteosarcoma and those with ordinary osteosarcoma.7
Fig. 3A: An axial CT section through the distal femur reveals extensive osteolysis with intralesional sclerosis, cortical destruction and a prominent soft tissue component. The neurovascular bundle (arrow) appears uninvolved; however, this is best assessed by scanning during intravenous infusion of contrast.
Fig. 3B: An axial CT section 3 cm proximal reveals intramedullary tumor and a large soft tissue mass, obliterating the vastus medialis muscle and posteriorly displacing the semimembranosus (open arrow) and sartorius (closed arrow) muscles. The neurovascular bundle (arrowhead) appears uninvolved at this level.
Fig. 4: CT examination of the lungs reveals two parenchymal nodules (arrows) and a small subpleural nodule (arrowhead).
Telangiectatic osteosarcoma comprises between 2% and 12% of osteosarcomas.4-9 The age and sex distribution and clinical signs and symptoms are the same as tiiose of ordinary osteosarcoma. Pain and swelling are the most frequent and characteristic symptoms. The distal femur is a favored site of involvement, followed in frequency by the proximal humerus, proximal tibia and femoral diaphysis. Pathologic fracture, reported in 24% to 29% of patients, occurs with significantly greater frequency than in other osteosarcomas.5·7
The criteria for diagnosis7 are: I) a predominantly lytic, destructive lesion of bone with only minimal lesionai sclerosis on roentgenograms; 2) a soft, cystic, cavity-like tumor on gross examination; and 3} histologically, single or multiple aneurysmally dilated spaces, containing blood or necrotic tumor cells, lined or traversed by septa composed of anaplastic sarcoma cells with numerous mitoses. Scanty, lace- like osteoid, produced by sarcoma cells, is observed. Since conventional osteosarcoma may show areas of hemorrhage on a degenerative basis, at least 90% of the tumor must show telangiectatic features, grossly and microscopically, to ensure the diagnosis.
Histologic Appearance and Differential Diagnosis
The gross appearance of telangiectatic osteosarcoma is that of a cavity or cavities filled with clotted blood associated with destruction of cortical bone and extension into the adjacent soft tissue. Only small areas of solid tumor are found. The histologic differential diagnosis includes aneurysmal bone cyst (ABC), giant cell tumor of bone and hemangioendothelioma. On lower power microscopic examination, telangiectatic osteosarcoma resembles an ABC with large, blood-filled cystic spaces traversed by septa. However, on closer examination telangiectatic osteosarcoma is distinguished by the pronounced anaplasia of the cystic lining cells and of the cells within the septa. These ceils demonstrate an increase in the nucleocytoplasmic ratio and enlarged hyperchromatic nuclei that vary in size, shape and staining qualities. Numerous, aberrant mitotic figures and clusters of benign giant cells are usually present. Lace-like osteoid is produced by sarcoma cells in the septa and in the more solid areas of die tumor.
Fig. 5: A chest radiograph taken four months later reveals multiple, bilateral, variable-sized pulmonary nodules and masses, bilateral pneumothoraces and a right pleural effusion. Pneumothorax is not uncommon with osteosarcomatous pulmonary metastases and rarely may represent the first evidence of metastatic disease.
In contrast, the dilated cystic spaces of an ABC are traversed by fibrous connective tissue septa whose cells reveal no cellular anaplasia or atypical mitoses. Confusion with giant cell tumor may occur; however, the stromal cells of giant cell tumor lack anaplasia and, although giant cell tumor may have cystic areas, septal formation is usually absent. Hemangioendothelial sarcoma of bone may also contain large, blood-filled spaces; however, septal formation is uncommon. This tumor is characterized by the formation of anastamosing vascular channels lined by "crowded" neoplastic endothelial cells.'0 In telangiectatic osteosarcoma, only the cystic spaces are lined by tumor cells and an anastamosing pattern is not seen.
Radiographic Appearance and Differential Diagnosis
Telangiectatic osteosarcoma usually involves the metaphyseal region of a tubular bone and there is predilection for the bones about the knee and the proximal humerus. A tendency to extend into the epiphysis and up to the articular cartilage has been described.5 The radiographic appearance of telangiectatic osteosarcoma is usually one of a lytic, destructive lesion with perhaps minimal intralesional sclerosis and poorly defined margins. An increased frequency of pathologic fracture is observed, reflecting extensive bony destruction and a lack of solid tumor, A blown-out pattern with a large soft tissue component is common. Periosteal reaction is an inconstant finding and, when present, may be of the laminated or spiculated type. In some cases, especially when the tumor is small, the lesion may be sharply delimited and not display obviously aggressive or malignant radiographic features. In fact, when all forms of purely lytic or predominantly lytic osteosarcoma are studied, from 3% to 7% present with radiographically benign features.11·12 In such cases, the differential diagnosis includes such benign entities as eosinophilic granuloma, ABC, giant cell tumor and Brodie's abscess. The radiographic demonstration of focal cortical destruction, irregular periosteal new bone or an extraosseous soft tissue component would suggest the diagnosis of an aggressive, possibly malignant, process. Rapid diagnosis may usually be achieved by performing a percutaneous needle biopsy of the lesion.
The. majority of telangiectatic osteosarcomas appear radiographically as an aggressive lytic process and the differential diagnosis includes malignant fibrous histiocytoma, central medullary fibrosarcoma of bone, metastatic disease, plasmaceli myeloma, giant cell tumor, and an aggressive ABC. In most instances, biopsy of the lesion will lead to the correct diagnosis or narrow the differential diagnosis considerably, as previously discussed. However, a significant potential exists for misdiagnosis, on both radiographic and histologic grounds, of the lesion as an ABC. Alternatively, in two separate reports, four cases of ABC were erroneously diagnosed as osteosarcoma.13·14 In two cases, unnecessary amputations were performed based on "clinical evidence" without histologic confirmation.13 The clinical evidence and radiographic findings are not sufficiently specific in all cases to permit accurate diagnosis.
In the presence of an open growth plate, extension into the epiphysis may commonly occur with osteosarcoma,15 but has been considered rare with ABC. However, a recent report describes invasion of an open growth plate in 23% of juxtaepiphyseal ABCs, the majority of which were aggressive ABCs. 16 This suggests that the presence of epiphyseal extension cannot be used to reliably exclude ABC. The presence of cortical expansion and a reactive bony shell strongly suggests a benign or slow-growing process, such as ABC. However, an aggressive, rapidly growing ABC may have ill-defined margins without delimiting reparative bone or periosteal shell and may even have a soft tissue component. I7 A giant cell tumor may also have this appearance and often extends up to the articular cartilage. Such lesions should be treated as malignant until proven otherwise and the correct diagnosis rests upon accurate reading of a representative histologic section from the lesion. In some cases, the soft tissue component may be encircled by thin periosteal new bone formation, thereby indicating the benign nature of the lesion.
The prognosis in telangiectatic osteosarcoma has been reported in two studies as worse than conventional osteosarcoma.4·5 However, a recent, larger study of 124 patients concluded that survival is no different in patients with telangiectatic osteosarcoma.7 They reported two year and five year survival of 40% and 27% respectively for telangiectatic osteosarcoma and 48% and 25% respectively for all other forms of osteosarcoma. These investigators also separated those patients with a purely lytic radiographic presentation from those with minimal sclerosis and found no difference in survival. The routine use of multidrug chemotherapy in conjunction with surgery, beginning in 1975, has resulted in a dramatic increase in disease-free survival in all patients with osteosarcoma.18 A 93% disease-free survival at a median of 20 months from the start of chemotherapy has been reported. ,9 In patients with telangiectatic osteosarcoma treated since 1975, two year actual survival has increased from 32% to 85%.*> When this treatment approach was applied to 11 patients with telangiectatic osteosarcoma with no evidence of pulmonary metastasis at the time of surgery for the primary tumor, an 82% complete response rate was obtained.7 When this is compared to a 49% complete response rate obtained in similarly treated patients with other variants of osteosarcoma, it appears that telangiectatic osteosarcoma may be more responsive to modern chemotherapy than other types.
The application of preoperative chemotherapy to treatment of the primary tumor in patients with osteosarcoma came about partly as an outgrowth of limb salvage surgery. Preceding work had demonstrated that chemotherapeutic agents could be effective in producing regression of pulmonary metastases. When used in conjunction with thoracotomy, prolonged disease-free survival was sometimes obtained.20 This approach was then applied to patients undergoing limb salvage surgery. Patients were given preoperative chemotherapy in an attempt to contain the primary tumor during the two to three months spent waiting for custom production of an endoprosthesis. The efficacy of various chemotherapeutic agents could be assessed by examining the extent of tumor necrosis within the resected specimen. The current approach to patients with osteosarcoma of an extremity without evidence of metastatic disease is a 4 to 16 week course of high dose methotrexate and citrovorum factor rescue, Adriamycin, bleomycin, cyclophosphamide, and dactinomycin followed by definitive surgery. Patients having a favorable effect of chemotherapy on the primary tumor (based on histologic examination of the resected specimen) are continued on the same regimen postoperatively. In patients not having a good effect, methotrexate is replaced by cis-platinum and this is given in combination with the other agents.19
This therapeutic approach offers the following advantages: 1) early institution of systemic chemotherapy to eradicate micrometastases which could eventually lead to the patient's death; 2) reduction in bulk and size of primary tumors, frequenüy making limb salvage surgery possible; 3) provide the surgeon time to plan resection; 4) definition of the optimal adjuvant chemotherapeutic agents and optimal dose for each patient; and 5) identification of high risk patients who require additional chemotherapy to control tumor growth.
The successful management of patients with osteosarcoma, presenting without evidence of metastatic disease, also depends on early detection of pulmonary metastases. Dissemination of osteosarcoma occurs by the hematogenous route and tumor cells are trapped in the pulmonary capillary bed. The lungs initially will be the sole site of metastases in virtually all patients with osteosarcoma. Post-mortem studies have demonstrated that a large number of patients with osteosarcoma died with metastases to the lung as the only evidence of disseminated disease21; and many such lesions were later judged resectable.22 Monthly or periodic roentgenographic follow up is, therefore, essential and when pulmonary nodules are detected, CT should be performed in an effort to quantify the degree of pulmonary involvement.23,24
In patients with metastatic disease confined to the lung, that is unresponsive to chemotherapy, surgical excision should be attempted (unless there are signs of inoperability).20 Osteosarcoma cells tend to migrate to and inplant in peripheral or subpleural sites in the lung, lending themselves to wedge resection.25 When patients who develop pulmonary metastases are treated by aggressive, sometimes multiple, thoracotomies an actuarial survival of 31% to 54% may be achieved.26"28 Unfortunately, patients do not do as well when pulmonary metastases are evident at the time of initial diagnosis of osteosarcoma. In one study, survival in such patients did not exceed 16 months. even with resection of all detectable tumors.26
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Section Editor: Terrence C. Demos, MD