Laboratory Studies
Most recommended laboratory studies are related to the use of chemotherapy. Therefore, assessing organ function before, during, and after chemotherapy is important.
The only blood tests with prognostic significance are measurements of lactate dehydrogenase (LDH) and alkaline phosphatase levels. Patients with elevated alkaline phosphatase values at diagnosis are more likely than others to have pulmonary metastases. Patients without metastases with an elevated LDH level are less likely to do well than those with an LDH level in the reference range.
Important laboratory studies include tests of the following:
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CBC count, including differential and platelet count
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Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and albumin levels to assess liver function
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Electrolyte concentrations, including sodium, potassium, chloride, bicarbonate, calcium, magnesium, and phosphorus levels
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BUN and creatinine values to assess renal function
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Urine (urinalysis)
Imaging Studies
Imaging studies are listed below:
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Plain radiography
Plain radiography of the suspected lesions should be performed using 2 views (see images shown below).
Lateral plain radiograph of the knee reveals an osteosarcoma of the distal femur. The lesion is mainly posterior, with disruption and elevation of the periosteum (Codman triangle), and extends beyond the bone into the soft tissue.
Anteroposterior plain radiograph of the same with distal femoral osteosarcoma as shown in image above. The osteolytic lesion is apparent on the right side of the image.
No single feature on radiographs is diagnostic. Osteosarcomatous lesions can be purely osteolytic (about 30% of patients), purely osteoblastic (about 45% of patients), or a mixture of both.
Elevation of the periosteum may appear as the characteristic Codman triangle. Extension of tumor through the periosteum may result in a so-called sunburst appearance (about 60% of patients).
The entire bone and adjacent joint should be imaged to assess for skip lesions and joint involvement.
Telangiectatic osteosarcomas are often cystic and can be mistaken for an aneurysmal bone cyst.
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Chest radiography: Chest radiographs (posteroanterior and lateral views) should be obtained to evaluate for pulmonary metastases. If metastases are present and visible on chest images, this modality then can be used for follow-up of specific lesions.
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CT scanning
Both a CT scan of the primary lesion and a high-resolution CT scan of the chest (at 3.75-mm to 7.5-mm intervals) should be obtained.
CT scanning of the primary lesion helps in delineating the location and extent of the tumor and is critical for surgical planning.
CT scanning of the chest is more sensitive than plain radiography for assessing pulmonary metastases. In the ideal situation, the chest CT scan should be obtained before biopsy to avoid ambiguity that can arise from postanesthesia atelectasis.
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Magnetic resonance imaging
MRI of the primary lesion is the best method for assessing the extent of intramedullary disease. See the following images.
MRI of the same distal femoral osteosarcoma as in images shown under the plain radiography section above; the uninvolved side is shown for comparison.
Close-up MRI of the same distal femoral osteosarcoma as shown in image above, and in images shown under the plain radiography section above.
MRI findings are best correlated with the extent of disease assessed at the time of definitive surgery.
MRI should include joint-to-joint imaging to rule out skip lesions.
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Radionuclide bone scanning with technetium-99m diphosphonate
An evaluation for the presence of metastatic or multifocal disease with bone scanning is imperative.
Abnormal areas should subsequently be imaged using CT scanning or MRI.
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18F-Fluoro-deoxy-glucose positron emission tomography (PET) or thallium-201 scintigraphy
The use of these radionuclide studies for diagnostic and prognostic purposes in osteosarcoma is still under investigation. [20]
Initial published data suggest the results of these can be more predictive of the response to chemotherapy than MRI or CT findings [21] and can detect disease missed by conventional imaging. [22]
Changes in PET scan findings with neoadjuvant chemotherapy appear to be predictive of histologic response. [23]
Other Tests
Other tests include the following:
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Audiography: Hearing loss is an adverse effect of cisplatin.
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Echocardiography or multiple-gated acquisition (MUGA) scanning: Cardiac function should be assessed before and at various intervals after treatment with doxorubicin (Adriamycin).
Procedures
An orthopedic surgeon should perform biopsy (see Surgical Care).
Resections of the primary lesion and of any pulmonary metastases are essential for cure. These should be performed by orthopedic and thoracic surgeons, respectively (see Surgical Care).
Presurgical (neoadjuvant) chemotherapy often aids resection by shrinking tumors and enables the assessment of histopathologic responsiveness of the tumor, a major predictor of the outcome.
Histologic Findings
Upon histologic examination of the tumor, two elements are important. The first important element, the type of the tumor, can be assessed by examining the biopsy specimen. The second important element, the response to treatment, can be assessed only by evaluating the tissue resected after chemotherapy.
In general, the characteristic feature of osteosarcoma is the presence of osteoid in the lesion, even at sites distant from bone (eg, the lung). Although osteoid is usually obvious, electron microscopy is occasionally required to visualize its formation. Stromal cells may be spindle shaped and atypical with irregularly shaped nuclei.
Numerous distinct histologic types of osteosarcoma are described. The conventional type is the most common in childhood and adolescence. This type has been subdivided on the basis of the predominant features of the cells (ie, osteoblastic, chondroblastic, fibroblastic types), although the subtypes are clinically indistinguishable. The telangiectatic type contains large blood-filled spaces and is common in adolescence and early adulthood. [24] The parosteal type is usually located in the bony cortex, is easier to cure than the conventional type, and can be seen in childhood or adulthood. The low-grade periosteal type, which also arises from the cortex but usually encircles the bone, most often occurs in older patients who have a long history of symptoms, which reflects its indolent nature.
Staging
The purpose of staging tumors is to stratify risk groups. The conventional staging system used for other solid tumors is not appropriate for skeletal tumors because these tumors rarely involve lymph nodes or spread regionally. Rather, the staging system Enneking devised is based on grade, extramedullary spread, and metastases. These features are most important for nonmalignant skeletal tumors; most osteosarcomas are highly malignant. For osteosarcoma, the foremost initial question regarding staging is whether the tumor has metastasized.
Other features of the tumor, although technically not used in staging, may affect the prognosis. These include the site of primary tumor (mostly related to difficulty of obtaining a complete resection, such as with pelvic tumors), [25] the histologic response to chemotherapy, and the cause of disease. Patients with a good histologic response before surgery, the definition of which is still debated (generally >90% or >95% necrosis), appear to have an improved prognosis. [26] Those with only one metastasis appear to do better than those with multiple metastases. [19] Those with lesions that arise from Paget disease have a particularly poor prognosis. Patients with isolated lesions of the jaw tend to do better and have a relatively low incidence of metastases.
Other features are being investigated for their prognostic significance. Examples include cellular expression of membrane-type matrix metalloproteinase type 1, Fas, CXCR4, [27] Twist, microvessel density, [28, 29] P-glycoprotein expression, [30] and microarray signatures. Each of these features was prognostic in small series; however, none have been tested prospectively, and testing for them has not yet become standard of care. The presence of metastases and a histologic response remain the most important predictors of outcome. Serum markers lose their significance when they are considered in multivariate analysis.
The osteosarcoma staging system can be summarized as follows:
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Stages
Stage I - Low-grade lesions
Stage II - High-grade lesions
Stage III - Metastatic disease
Substages
A - Intramedullary lesion
B - Local extramedullary spread
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Site of primary
Distal extremity - Best prognosis
Distal femur - Intermediate prognosis
Axial skeleton - Worst prognosis
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Lateral plain radiograph of the knee reveals an osteosarcoma of the distal femur. The lesion is mainly posterior, with disruption and elevation of the periosteum (Codman triangle), and extends beyond the bone into the soft tissue.
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Anteroposterior plain radiograph of the same with distal femoral osteosarcoma as shown in image above. The osteolytic lesion is apparent on the right side of the image.
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MRI of the same distal femoral osteosarcoma as in images shown under the plain radiography section above; the uninvolved side is shown for comparison.
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Close-up MRI of the same distal femoral osteosarcoma as shown in image above, and in images shown under the plain radiography section above.
