Bone Tumors

The big picture: metastases and myeloma first

Metastasis is the most common bone tumor. Secondary deposits vastly outnumber primary bone tumors. The usual sources are breast, prostate, lung, kidney, and thyroid, and the spine is the most common site; prostate cancer can reach the vertebrae through the valveless vertebral (Batson) venous plexus.

Blastic vs lytic. Prostate metastases are classically osteoblastic, laying down dense sclerotic bone. Kidney, thyroid, and lung metastases are osteolytic, producing punched-out lucencies from bone destruction; breast metastases are mixed. Lytic destruction weakens bone, so these deposits present with pain, pathologic fracture, and hypercalcemia. An older man with multiple sclerotic vertebral lesions and a markedly elevated PSA has metastatic prostate carcinoma.

Multiple myeloma. The most common primary bone malignancy is multiple myeloma, a plasma cell neoplasm that produces punched-out lytic lesions. Because these lesions provoke little osteoblastic response, a radionuclide bone scan can miss them.

Benign bone tumors

Osteochondroma. The most common benign bone tumor, typically in males under 25. It is a cartilage-capped bony outgrowth (exostosis) from the metaphysis whose cortex and marrow are continuous with the parent bone, and it points away from the nearest growth plate. Malignant transformation of the cartilage cap to chondrosarcoma is rare; the risk is higher with multiple hereditary exostoses (autosomal dominant EXT1/EXT2 mutations).

Osteoid osteoma. A small (under 2 cm) radiolucent nidus surrounded by a sclerotic rim, located in the cortex of long bones (femur, tibia) of young men. The nidus produces prostaglandins, so the pain is worse at night and reliably relieved by NSAIDs or aspirin.

Giant cell tumor (osteoclastoma). Arises in the epiphysis of long bones around the knee (distal femur, proximal tibia) in adults aged 20–40. X-ray shows a lytic "soap-bubble" lesion. Histology shows multinucleated osteoclast-like giant cells among mononuclear stromal cells; the neoplastic stromal cells express RANKL, which recruits the giant cells. It is benign but locally aggressive and tends to recur after curettage.

Enchondroma. A benign hyaline cartilage tumor within the medullary cavity, most often in the small bones of the hands and feet. Multiple enchondromas (Ollier disease; Maffucci syndrome when combined with soft-tissue hemangiomas) raise the risk of chondrosarcoma.

Malignant primary bone tumors

Osteosarcoma. The 2nd most common primary bone malignancy (after multiple myeloma) and the most common primary bone sarcoma. Malignant cells produce osteoid. It arises in the metaphysis around the knee (distal femur, proximal tibia) and in the proximal humerus. X-ray shows a Codman triangle (periosteum elevated by tumor) and a spiculated sunburst pattern. Hematogenous spread goes mainly to the lungs.

Bimodal age and risk factors. One peak occurs in males aged 10–20 (growth spurt) and a second in the elderly. Risk factors are Paget disease of bone, prior radiation, familial retinoblastoma (RB1), and Li-Fraumeni syndrome (TP53).

A child treated for retinoblastoma who later develops a bone tumor around the knee has RB1-associated osteosarcoma.

Ewing sarcoma. Strikes boys under 15 in the diaphysis of long bones and the pelvis. X-ray shows a lamellated onion-skin periosteal reaction; histology shows sheets of anaplastic small round blue cells that are PAS-positive (glycogen) and CD99-positive. It is driven by the t(11;22) EWSR1-FLI1 fusion and is aggressive but chemosensitive. Fever, leukocytosis, and a raised ESR can make it mimic osteomyelitis.

Ewing = 11 + 22 = 33: small round blue cells of the diaphysis in a young boy.

Chondrosarcoma. A malignant cartilage-forming tumor of adults over 50, arising in the medullary cavity of the central skeleton: pelvis, proximal femur, or proximal humerus. It produces cartilage matrix, may arise de novo or from an osteochondroma or enchondroma, and is treated mainly by surgery.

Reading the X-ray: zone and aggressiveness

Location maps to diagnosis. Around the knee (distal femur, proximal tibia) is the classic hot spot for both giant cell tumor and osteosarcoma, so the zone of the long bone separates them.

Aggressive tumors show periosteal reaction. Benign lesions are well circumscribed with sclerotic margins. Malignant lesions have a wide zone of transition, moth-eaten or permeative lysis, cortical destruction, and periosteal reaction.

Age patterns and clinical approach

Age narrows the differential. Children and teens get Ewing sarcoma (diaphysis, under 15) and primary osteosarcoma (10–20). Young adults aged 20–40 get giant cell tumor. Older adults over 50 get chondrosarcoma, metastasis, and Paget-associated osteosarcoma.

Workup. Persistent bone pain, a palpable mass, or a pathologic fracture warrants a plain X-ray first, then MRI to define extent, then biopsy for tissue diagnosis.

In adults over 40, a destructive bone lesion is metastasis or multiple myeloma until proven otherwise; look for a primary tumor and order serum and urine protein electrophoresis for myeloma.