metastatic bone tumor

**Epidemiology:** Metastases are the most common malignant bone tumor in adults (>40 years). In children, think primary tumors (osteosarcoma, Ewing sarcoma) or metastatic neuroblastoma. Mnemonic for primaries that commonly metastasize to bone: "PB KTL" (Prostate, Breast, Kidney, Thyroid, Lung). Mnemonic: "Lead, Kills, Bone, Pain" or "BLT with a Kosher Pickle" (Breast, Lung, Thyroid, Kidney, Prostate).

**Pathophysiology:** Spread is mainly hematogenous. Batson's venous plexus (valveless vertebral venous plexus) allows retrograde spread from pelvic organs (prostate) and breast to the vertebral column, bypassing the lungs. Red marrow-rich sites (axial skeleton, proximal long bones) are favored because of slow blood flow and a favorable microenvironment. Tumor cells interact with the bone microenvironment ("vicious cycle"): tumor cells secrete PTHrP, IL-6, and RANKL-stimulating factors, which activate osteoclasts via the RANK/RANKL pathway. Bone breakdown releases growth factors (TGF-β, IGF) that feed tumor growth.

**Radiographic patterns:** - **Osteolytic (lucent):** Most common overall. Seen in lung, kidney, thyroid, breast (often mixed), multiple myeloma (punched-out lesions; technically a primary marrow malignancy). Renal and thyroid cancers produce "blow-out" expansile lytic lesions. - **Osteoblastic (sclerotic):** Prostate (classic; elevated PSA and alkaline phosphatase), also breast, carcinoid, and Hodgkin lymphoma ("ivory vertebra"). - **Mixed:** Breast, lung. - Vertebral pedicle erosion ("winking owl sign" on AP spine X-ray) is a classic finding for metastasis.

**Clinical presentation:** - Progressive, nocturnal, unremitting bone pain (the most common symptom) - Pathologic fractures (especially with lytic lesions) - Hypercalcemia of malignancy (osteolysis and PTHrP) - Spinal cord compression (an oncologic emergency: back pain, weakness, sensory level, bowel/bladder dysfunction) - Bone marrow infiltration (leukoerythroblastic anemia, pancytopenia) - Labs: ↑ alkaline phosphatase (especially with osteoblastic lesions), ↑ calcium (lytic lesions). Phosphate is often normal or low.

**Diagnosis:** Plain films, bone scan (technetium-99m; sensitive but poor for purely lytic lesions such as myeloma), MRI (best for spine and cord compression), PET/CT. Biopsy is needed if the primary is unknown.

**Management:** - Treat the primary cancer (hormonal therapy for prostate and breast) - Palliative radiation for pain - Bisphosphonates (zoledronic acid) or denosumab (anti-RANKL monoclonal antibody) to reduce skeletal-related events - Surgical fixation for impending or actual pathologic fractures - Emergent high-dose dexamethasone plus MRI and radiation or surgery for cord compression - Radiopharmaceuticals (radium-223, strontium-89) for osteoblastic disease

**High-yield pearls:** - Metastasis is more common than primary bone cancer in adults. - The most common primary malignant bone tumor in adults is multiple myeloma. Osteosarcoma is the most common non-hematologic primary bone tumor overall, with a bimodal distribution (adolescents and older adults with Paget disease). - Hypercalcemia of malignancy has two main mechanisms: PTHrP secretion (humoral, e.g., squamous cell lung cancer) and local osteolytic metastases (e.g., breast cancer, myeloma). - Hands and feet are rarely involved, but lung cancer can metastasize to the distal phalanges.