The most sensitive indicator of metastatic disease is bone scintigraphy, which appears positive when as little as 5-15% of the trabecular bone is destroyed by tumor . This technique is much more sensitive than plain bone radiographs and shows metastases to bone much earlier. Indeed, only 3% of bone metastases will be seen on plain bone radiographs in the face of a normal bone scan. The mechanism involved in the uptake of the radiopharmaceutical used in bone scin-tigraphy is not well understood. Usually technetium-99m (99mTc)-labeled diphos-phonate is used. This radiopharmaceutical will localize on the images to show an area of increased bone formation or blood flow, resulting in a ''hot spot'' on the images . When metastatic tumor invades bone it causes local bone destruction, but new bone formation will simultaneously occur as a response. The radio-pharmaceutical appears to bind to the hydroxyapatite crystal of this new bone and not to the tumor cells themselves.
Rarely, there may be areas of decreased blood flow or decreased or absent new bone formation in the face of metastatic tumor in the bone that will result in a localized area of decreased tracer uptake, known as a photopenic lesion . Rapid bone resorption without new bone formation may rarely occur with an aggressive, highly destructive metastatic tumor. In this case, the 99mTc-diphospho-nate may not be taken up in the area of bone destruction. However, most lesions are visualized through increased tracer uptake.
Table 2 Conditions Causing Increased Uptake of 99mTc-Diphosphonate on Bone Scintigraphy
Aseptic necrosis, cysts Bone infarct Eosinophilic granuloma Fibrous dysplasia Fracture (recent or healing) Heterotopic bone growth Hyperostosis frontalis interna Osteitis pubis Osteoid osteoma Osteomyelitis, osteitis Paget's disease Postsurgical bony changes Renal osteodystrophy Rheostosis Sudeck's atrophy Soft-tissue abnormalities
Hydronephrosis or hydroureter Injection site Postsurgical scar Soft-tissue osseous metaplasia Primary malignant bone tumors Chondrosarcoma Ewing's sarcoma Osteosarcoma Benign bone tumors Fibroma
Chondroma and enchondroma Normal structures Alae of sacrum Base of skull Epiphyses of youth Facial bones Inferior tip of scapula Kidneys and bladder
Sternomanubrial and corpus-manubrial joints Thyroid cartilage Variant anatomy Artifacts from spillage of isotope during injection Antecubital fossa Lateral chest wall Metastatic tumors
Bone scintigraphy is undoubtedly quite sensitive but not very specific for definitively confirming metastatic tumor. A wide variety of benign and malignant conditions other than metastatic disease may result in increased uptake of the tracer, as listed in Table 2. Because there are so many causes of tracer accumulation, there is a real possibility that a ''positive'' bone scan is in fact a false positive result when the images are used in the staging of a malignancy, especially if considered without other modality studies. Therefore, the presence of a positive (although nonspecific) bone scan mandates biopsy of the suspected lesion for histological confirmation of a possible metastasis, especially in the absence of definite, abnormal plain bone radiographs. Only after a diagnostic biopsy can the stage of the disease be reliably established.
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