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as prostaglandin-E and procathepsin-D, or by inducing macrophages and other cells of the immune system to release tumor necrosis factor and interleukin-1. Increased osteoclastic activity at tumor sites may also be due to systemic factors such as parathyroid hormone-related protein and transforming growth factors alpha and beta. Not all the observed events related to the metastatic process have been fully explained at the molecular level and the subject is still under scientific investigation.

Interpretation of Bone Scans

When multiple foci of increased uptake are scattered randomly in the axial and proximal appendicular skeleton the diagnosis of metastatic disease is not difficult (Fig. 7). Given the low specificity of radiophosphate imaging and its sensitivity to increased bone remodeling from any cause, whether benign or malignant, the presence of one or just a few lesions renders the interpretation more difficult. An analysis of scans with one or two bone lesions in cancer patients without known metastases showed that 11% of single lesions were malignant, and 30% of the patients with two lesions proved to be malignant. About 10% of isolated rib uptakes reflect a metastasis. Location may help in the differentiation as benign lesions are more common at articular surfaces of joints in the vertebral column and extremities, suture lines of the skull, anterior rib ends and costovertebral joints. Metastases beyond the elbows and knees are infrequent. An increase in lesion uptake over time in serial studies favors a diagnosis of malignancy, particularly if new ones also appear; lesions that remain stable or wane in intensity are most likely benign.

The radiophosphate portrayal of a very high diffuse concentration in bone, low soft tissue activity and virtually undetected kidneys is referred to as a "super scan" (Fig. 8). This is encountered mostly in prostatic cancers. On close inspection, with

Figure 7. Skeletal metastases from prostatic carcinoma. Anterior and posterior total body scans show multiple focal sites of intense uptake involving both the axial and appendicular skeleton. (Case provided by Dr. W.D. Leslie.)

varying contrast settings, many will reveal a heterogenous rather than homogeneous distribution. With successful treatment the bone scan can revert to normal or a presentation of multiple focal abnormalities and the usual soft tissue background and visible kidneys.

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