About 27% of all cancer patients have some metastases at autopsy. Any carcinoma, lymphoma, or sarcoma may metastasize to bone, although those primary in certain organs do so much more frequently than others. Prostate, breast, lung, kidney, and thyroid are the most common carcinomas. Once in bone they may cause local destruction that is manifested on x-ray film by an osteolytic lesion. In many cases there is osseous reaction surrounding the tumor with the formation of new bone or osteoid, and with sufficient degree of reaction this appears on x-ray films as an osteoblastic lesion. Prostate carcinoma is usually osteoblastic on x-ray film. Breast and lung carcinomas are more commonly osteolytic, but a significant number are osteoblastic. The others usually have an osteolytic appearance.

Hematologic. About one half of the carcinomas metastatic to bone replace or at least injure bone marrow to such an extent as to give hematologic symptoms. This must be distinguished from the anemia of neoplasia, which appears in a considerable number of patients without direct marrow involvement and whose mechanism may be hemolytic, toxic depression of marrow production, or unknown. The degree of actual bone marrow replacement is often relatively small in relation to the total amount of bone marrow, and some sort of toxic influence of the cancer on the blood-forming elements has been postulated. Whatever the mechanism, about one half of patients with metastatic carcinoma to bone have anemia when first seen (i.e., a hemoglobin value at least 2 gm/100 ml [20 g/L] below the lower limit of the reference range). When the hemoglobin value is less than 8 gm/100 ml (80 g/L), nucleated red blood cells (RBCs) and immature white blood cells (WBCs) may appear in the peripheral blood, and thrombocytopenia may be present. By this time there is often extensive marrow replacement.

Therefore, one peripheral blood finding that is always suspicious of extensive marrow replacement is the presence of thrombocytopenia in a patient with known cancer (unless the patient is on cytotoxic therapy). Another is the appearance of nucleated RBCs in the peripheral blood, sometimes in addition to slightly more immature WBCs. This does not occur in multiple myeloma, even though this disease often produces discrete bone lesions on x-ray film and the malignant plasma cells may replace much of the bone marrow.

Alkaline phosphatase. Because of bone destruction and local attempts at repair, the serum alkaline phosphatase level is often elevated. Roughly one third of patients with metastatic carcinomas to bone from lung, kidney, or thyroid have elevated alkaline phosphatase levels on first examination. This is seen in up to 50% of patients with breast carcinoma and 70%–90% of patients with prostate carcinoma.

Bone x-ray film. If an x-ray skeletal survey is done, bone lesions will be seen in approximately 50% of patients with actual bone metastases. More are not detected on first examination because lesions must be more than 1.5 cm to be seen on x-ray films, because parts of the bone are obscured by overlying structures, and because the tumor spread may be concealed by new bone formation. Almost any bone may be affected, but the vertebral column is by far the most frequent.

Bone radionuclide scan. Bone scanning for metastases is available in most sizable institutions using radioactive isotopes of elements that take part in bone metabolism. Bone scanning detects 10%–40% more foci of metastatic carcinoma than x-ray film and is the method of choice in screening for bone metastases. A possible exception is breast carcinoma. Although bone scan is more sensitive for breast carcinoma metastasis than x-ray film, sufficient additional lesions are found by x-ray film to make skeletal surveys useful in addition to bone scanning. Also, in cases in which a single lesion or only a few lesions are detected by scan, x-ray film of the focal areas involved should be done since scans detect benign as well as malignant processes that alter bone (as long as osteoblastic activity is taking place), and the x-ray appearance may help to differentiate benign from malignant etiology. Bone scan is much more sensitive than bone marrow examination in patients with most types of metastatic carcinoma. However, tumors that seed in a more diffuse fashion, such as lung small cell carcinoma, neuroblastoma, and malignant lymphoma, are exceptions to this rule and could benefit from marrow biopsy in addition to scan.

Bone marrow examination. Bone marrow aspiration will demonstrate tumor cells in a certain number of patients with metastatic carcinoma to bone. Reports do not agree on whether there is any difference in positive yield between the sternum and iliac crest. Between 7% and 40% of the patients with tumor in the bone have been said to have a positive bone marrow result. This varies with the site of primary tumor, whether the marrow is tested early or late in the disease, and whether random aspiration or aspiration from x-ray lesions is performed. The true incidence of positive marrow results is probably about 15%. Prostatic carcinoma has the highest rate of yield, since this tumor metastasizes to bone the most frequently, mostly to the vertebral column and pelvic bones. Lung small cell (oat cell) carcinoma, neuroblastoma, and malignant lymphoma also have a reasonable chance of detection by bone marrow aspiration.

Several studies have shown that marrow aspiration clot sections detect more tumor than marrow smears and that needle biopsy locates tumor more often than clot section. Two needle biopsies are said to produce approximately 30% more positive results than only one.

The question often arises as to the value of bone marrow aspiration in suspected metastatic carcinoma to bone. In this regard, the following statements seem valid:

1. It usually is difficult or often impossible to determine either the exact tumor type or the origin (primary site) of tumor cells from marrow aspiration.
2. If localized bone lesions exist on x-ray film and it becomes essential to determine their nature, a direct bone biopsy of these lesions using a special needle is much better than random marrow aspiration or even aspiration of the lesion area. In this way, a histologic tissue pattern may be obtained.
3. If a patient has a normal alkaline phosphatase level, no anemia, and no bone lesions on bone scan (or skeletal x-ray survey, if bone scan is not available), and in addition has a normal acid phosphatase level in cases of prostatic carcinoma, the chances of obtaining a positive bone marrow aspirate are less than 5% (exceptions are lung small cell carcinoma, lymphoma, and neuroblastoma).
4. If a patient has known carcinoma or definite evidence of carcinoma and x-ray lesions of bone, chemical studies or bone marrow aspiration usually have little practical value except in certain special situations in which anemia or thrombocytopenia may be caused by a disease that the patient has in addition to the carcinoma.