**4. Metastases from unknown site**

Patients over 40 years old who present with a painful new bone lesion should be investigated to mainly rule out bone metastasis or multiple myeloma [41].

Bone metastases occur in about 70% of advanced breast, lung, kidney, thyroid, and prostate carcinomas, while in gastrointestinal tumors, only 20% of patients have bone metastases, and among these patients, about half will present complications related to metastases, such as pathological fracture, spinal cord compression, pain requiring radiotherapy or surgery, and hypercalcemia, in about 10% of cases [42].

Breast and prostate cancers are the most common to generate bone metastases, however, when the patient has no diagnosis, the most common lesions to generate bone metastases are lung and kidney cancer [41]. Common sites of bone metastases are the proximal femur, pelvis, spine, ribs, and skull. Acral metastases are rare and they are usually related to lung cancer [42].

When evaluating patients with unknown site metastases, the focus is on finding the primary site of the neoplasm, and in about 85% of cases, a well-executed diagnostic evaluation can be successful to define de primary tumor. In the meantime, the evaluation begins with a comprehensive history and physical examination. Laboratory evaluation should include a complete blood count, erythrocyte sedimentation rate, alkaline phosphatase, liver function, renal function, thyroid function, electrolytes, PSA for men, and protein electrophoresis. Imaging evaluation begins with radiography of the lesion and the entire skeleton, as well as bone scintigraphy and CT scan of the chest, abdomen, and pelvis [41].
