Unlike skeletal metastasis of known origin (most often of the breast or prostate), a metastasis of unknown origin usually originates from the lung or kidney (although almost any visceral carcinoma can be the source of an occult malignancy). This could be attributed to the inaccessibility of these organs to physical examination, to the large size to which tumors in the kidney or lung can grow before becoming symptomatic, or to the tendency of these tumors to metastasize to bone earlier than breast or prostate carcinoma. Because the breast is a distinctly uncommon site for a metastatic malignant tumor when the patient has a skeletal metastasis of uncertain origin, a mammography should not be included as part of the evaluation unless the history or physical examination reveals an abnormality in the breast, or in those women who, after the diagnostic strategy has been completed, still have an unknown primary site [13].

A difficult clinical scenario is the occasional patient who presents to the orthopedist with a fracture that seems to be pathologic, yet the patient has no prior cancer history [14]. The problem here is to provide skeletal fixation, identify the tumor type, and not eliminate a limb-sparing operation if the tumor is a primary bone sarcoma. Working the patient up with CT of the chest, abdomen and pelvis and obtaining a whole body bone scan is challenging due to patient’s pain and difficulty in transferring. Depending on the fracture location and pain level of the patient at the time of presentation, blood testing and CT scans may be obtained prior to surgical intervention. A biopsy is needed at this point to rule out a primary sarcoma. It is much less important to identify the primary site in this scenario. Usually a needle biopsy of the lesion can be obtained either intraoperatively (before attempted fixation) or under radiographic guidance. If the needle biopsy is not diagnostic, an open or incisional biopsy is necessary. It is not appropriate to place internal fixation before a primary bone sarcoma is ruled out by biopsy. Sending reamings from the surgery after placing an intramedullary rod for skeletal fixation as the initial biopsy is inappropriate. Obviously if the lesion is a primary sarcoma of bone, limb salvage has been eliminated as an adequate local control measure in this patient. In addition, contamination of the buttocks with the entry site for a femoral intramedullary nail complicates the possible amputation level further. Referral to an orthopedic oncologist prior to biopsy is an appropriate consideration.

A second challenging scenario is a patient with a history of cancer presenting with a bone lesion and no prior history of metastases (see Figs. 10.1, 10.2, 10.3, and 10.4). Although this patient most likely has a metastatic lesion from their previous primary carcinoma, occasionally the bone lesion is either a second malignancy or a primary benign bone lesion (see Figs. 10.5 and 10.6). Assuming the bone lesion is malignant, this patient should be evaluated first with a bone scan (total body) to assess for other lesions. Multiple positive lesions will increase the likelihood that the lesions represent metastatic disease from the known primary site. CT of the chest/abdomen/pelvis should be taken to assess for other sites of metastatic disease or other initiating cancers. Needle or core biopsy generally should be done before treating the lesion to confirm the diagnosis of metastatic disease and to rule out a second primary cancer. It is inappropriate to begin any treatment of the first bone lesion without confirmatory biopsy. A biopsy specimen must be obtained before fixation in patients with an impending fracture.