What is a brown tumor in the context of hyperparathyroidism, particularly in older adults with a history of primary or secondary hyperparathyroidism?

What is a Brown Tumor?

A brown tumor is a rare, benign, focal lytic bone lesion caused by severe, long-standing hyperparathyroidism (either primary or secondary), resulting from chronic parathyroid hormone (PTH)-induced osteoclast activation that creates multinucleated giant cell conglomerates with hemosiderin deposits—not a true neoplasm, but rather an end-stage manifestation of uncontrolled bone remodeling. 1, 2

Pathophysiology

• Brown tumors develop from prolonged, elevated PTH levels that drive excessive osteoclast activation, leading to bone resorption and replacement with fibrous tissue containing multinucleated giant cells and hemosiderin deposits (which give the lesion its characteristic brown color on gross examination). 1

• This represents the terminal stage of bone remodeling in hyperparathyroidism, historically termed "osteitis fibrosa cystica." 3, 4

• The lesions are accompanied by local production of cytokines and growth factors that perpetuate the destructive process. 1

Epidemiology and Clinical Context

• Brown tumors occur in approximately 5% of patients with primary hyperparathyroidism and 13% of patients with secondary hyperparathyroidism (most commonly from chronic kidney disease). 4

• They are now rare in modern practice due to earlier detection and treatment of hyperparathyroidism, but may still occur with increased longevity of dialysis patients or in cases of poor compliance with medical management. 1, 5

• Critical distinction: Brown tumors must be differentiated from ossifying fibromas of the jaw, which occur in CDC73-related Hyperparathyroid-Jaw Tumor Syndrome—these are distinct entities, not the same as brown tumors. 6

Common Locations

• Most frequently affect the mandible, pelvis, ribs, and long bones. 2, 4

• Skull involvement (maxillary sinus, frontal bone) can occur but is less common. 5

• Axial spine involvement is rare but can present with neurological emergencies such as acute paraparesis requiring urgent surgical decompression. 4

Diagnostic Approach

Essential Laboratory Evaluation

• Obtain serum calcium (corrected for albumin) and intact parathyroid hormone (PTH) levels to establish the underlying hyperparathyroidism when evaluating any bone lesion suspected to be a brown tumor. 6, 7

• Expect PTH levels often exceeding 1000-2000 pg/mL in severe cases with brown tumors. 1

• Elevated serum bone turnover markers are typically present. 1

Imaging Characteristics

• Plain radiography and CT show expansile lytic lesions with thinned cortex. 6, 8

• MRI findings include heterogeneous signal intensity on T1 and T2-weighted images, with solid and cystic components; fluid-fluid levels may be present in the cystic areas. 8

• Dynamic contrast-enhanced MRI demonstrates marked early enhancement of solid areas with prolonged enhancement and septal/wall enhancement in cystic regions. 8

• Perform cross-sectional imaging (CT/MRI) to assess the extent of disease and identify additional lesions, as multiple brown tumors are common. 6

Histopathology

• Biopsy should be considered if diagnosis is uncertain, as brown tumors are frequently misdiagnosed as malignancy (including giant cell tumors or metastatic disease). 6, 1

• Histology reveals fibroblastic proliferation, abundant multinucleated giant cells, and focal hemosiderin deposition. 8

Management Strategy

Primary Treatment: Address the Underlying Hyperparathyroidism

• For primary hyperparathyroidism: Surgical excision of the parathyroid adenoma is the definitive treatment. 7, 1

• For secondary hyperparathyroidism: Medical management with vitamin D analogs and phosphate binders; surgical parathyroidectomy is reserved for medically refractory cases. 3, 1

• After successful treatment of hyperparathyroidism, brown tumors typically regress spontaneously and become sclerotic on follow-up radiographs. 8

Direct Surgical Intervention for Brown Tumors

• Direct resection of brown tumors is rarely necessary and reserved for specific indications: neurological compromise (e.g., spinal cord compression), pathological fractures, or when diagnosis remains uncertain despite workup. 1, 4

• In cases of acute paraparesis from spinal brown tumors, emergent operative decompression is warranted. 4

Post-Parathyroidectomy Considerations

• Monitor for hungry bone syndrome following parathyroidectomy in patients with severe, long-standing hyperparathyroidism and brown tumors, as rapid bone remineralization can cause profound hypocalcemia. 1

Clinical Pitfalls

• Do not mistake brown tumors for primary bone malignancies—always check calcium and PTH levels when evaluating lytic bone lesions. 6

• In patients with hypercalcemia and lytic lesions but absent brown tumor features, consider coincidental hyperparathyroidism; serum PTH measurements can confirm the diagnosis. 3

• Poor patient compliance and reduced adherence to treatment recommendations can lead to progression of brown tumors despite appropriate medical advice. 1

• Brown tumors in atypical locations (such as oral cavity) may not be included in initial differential diagnosis, delaying recognition of underlying hyperparathyroidism. 2