Brown tumor with secondary hyperparathyroidism

A brown tumor is a non-neoplastic, reactive osteolytic lesion of high-turnover bone disease produced by sustained parathyroid hormone (PTH)-driven osteoclastic resorption. In the secondary form, the driver is the hyperparathyroidism of chronic kidney disease (CKD): impaired calcitriol synthesis, phosphate retention, and hypocalcemia chronically stimulate the parathyroid glands, and the resulting osteoclast activity replaces resorbed bone with vascular fibrous tissue, hemorrhage, and hemosiderin—the deposits that give the lesion its brown color.[1][2] In the jaws the lesion favors the posterior mandible and the maxillary alveolus, where it appears as an expansile lytic lesion with a thin cortical shell on a background of generalized bone change.[3][4] The signature radiographic context is loss of lamina dura and a diffuse altered trabecular pattern reflecting the underlying metabolic disease. Because the histology is shared with other giant cell lesions, the diagnosis is secured by biochemistry, not microscopy alone, and management is directed first at the hyperparathyroidism rather than the bone lesion itself.[1][5]

• Brown tumor is the accepted term for the focal lytic lesion; it is not a true neoplasm despite the name.[1]
• Osteitis fibrosa cystica (von Recklinghausen disease of bone, first described in 1891) denotes the generalized high-turnover skeletal disorder of advanced hyperparathyroidism; brown tumors are its focal expression. The terms are related but not synonymous—osteitis fibrosa cystica is the systemic bone condition, the brown tumor its localized mass.[1][2]
• Osteoclastoma appears in older writing as a descriptor of the giant-cell content and is best avoided because it invites confusion with giant cell tumor of bone.[6][7]
• The qualifier secondary denotes compensatory PTH elevation, most commonly from CKD (also vitamin D deficiency or malabsorption), distinguishing it from primary (adenoma/hyperplasia) and tertiary (autonomous) disease, which produce histologically identical lesions.[1]

• Frequency is low and falling. Brown tumors complicate roughly 1.5–2% of secondary hyperparathyroidism and up to about 3–4.5% of primary disease; routine biochemical screening has made the lesion uncommon in high-income settings, while it persists where vitamin D deficiency and late diagnosis are common.[1][3]
• Underlying disease is prevalent. CKD affects an estimated 8–16% of adults worldwide, and secondary hyperparathyroidism develops in most patients with advanced CKD and on dialysis, so dialysis-dependent populations remain the main reservoir of cases.[2][11]
• Age and sex. Jaw brown tumors cluster in adults, with a female predominance and a peak in the third to fifth decades in maxillofacial series.[5]
• Anatomic distribution. Across the skeleton the pelvis, ribs, clavicle, long bones, and spine are typical; within the jaws the posterior mandible is the classic site, though maxillary alveolar involvement is well documented and predominated in at least one maxillofacial cohort. Lesions may be solitary or multiple.[1][4][5]

• Presentation is usually a slow, painless, bony-hard swelling with cortical expansion; some lesions enlarge rapidly and cause local discomfort, facial deformity, or interference with function.[8]
• Dental findings include tooth mobility, displacement, and malocclusion as the alveolar process expands, often with intact overlying mucosa.[9]
• Tempo and context. Many jaw lesions surface in a patient with established CKD on dialysis, or are found incidentally on dental imaging; the lesion may also be the first clue that prompts discovery of occult hyperparathyroidism, making recognition clinically consequential.[10]
• Systemic features reflect the metabolic disease rather than the mass: bone pain, fracture risk, and the mineral derangements of CKD-mineral and bone disorder.[11]
• Red flags. Multifocal lesions can mimic metastatic malignancy or myeloma and have led to unnecessary resection, radiotherapy, or amputation when the hyperparathyroid context was missed—an avoidable error given a single PTH measurement.[1]

Location and distribution

Jaw lesions arise most often in the posterior mandible, with the maxillary alveolar bone the next most common site; involvement may be solitary or multifocal, and multifocality should raise concern for widespread disease rather than independent tumors.[4][5] The lesion sits against a background of generalized skeletal change rather than otherwise normal bone.

Relationship to teeth and the alveolar process

• Loss of the lamina dura around tooth roots is the hallmark jaw finding of hyperparathyroidism and an important early clue.[12]
• Lesions expand the alveolar process and may displace teeth; the dentition often remains otherwise intact over the swelling.[9]

Periphery and shape

• Typically well-defined with a narrow zone of transition and a thin peripheral cortical shell; margins may be corticated without surrounding reactive sclerosis.[1][3]
• Shape ranges from round/ovoid unilocular to a multilocular, soap-bubble configuration in larger lesions.[3]

Internal architecture

• Predominantly radiolucent and lytic; larger lesions show internal septation producing the multilocular pattern.[3]
• A superimposed diffuse ground-glass alteration of the trabecular pattern with loss of normal trabeculation reflects the underlying renal osteodystrophy and can affect both jaws generally—an important contextual feature that distinguishes the metabolic setting from an isolated lesion.[9]

Effects on teeth and adjacent structures

• Cortical thinning and expansion are usual; frank cortical destruction or periosteal reaction is not expected and should prompt reconsideration.[3]
• Root resorption and tooth displacement can occur with larger lesions.[13]

Growth pattern and extent

• Growth is generally slow and expansile, but rapid enlargement is described and may dictate urgent intervention.[8]
• Extent varies from a confined alveolar lesion to large masses extending toward the sinus or displacing adjacent anatomy.[13]

Recognized variants

• Solitary jaw lesion versus multifocal skeletal disease; the latter resembles metastatic carcinoma or myeloma on survey imaging and is the pattern most prone to misdiagnosis.[1][7]
• Lesions that have responded to treatment show progressive sclerosis/ossification and infilling at the former lytic site.[8]

Giant cell lesions of the jaws share overlapping imaging and identical microscopy with the brown tumor, so the decisive maneuver in any giant-cell jaw lesion is biochemical screening (serum calcium, phosphate, PTH); the following entities are the highest-yield alternatives when those tests are not yet known.[1][14]

The dominant pitfall is treating a multifocal brown tumor as metastatic malignancy: hypercalcemia plus lytic bone lesions invites a cancer workup, yet a markedly elevated PTH distinguishes brown tumor instantly, and in the secondary form PTH is elevated in the setting of renal failure.[1][7] In secondary hyperparathyroidism, calcium is typically low-normal with elevated phosphate and PTH in the setting of CKD; hypercalcemia suggests tertiary disease or another cause. Conversely, a solitary giant cell lesion of the jaw with normal mineral chemistry should not be labeled a brown tumor. Biopsy confirms the giant-cell nature but cannot, by itself, separate these entities—laboratory correlation is mandatory before definitive surgery.[14]

• Core morphology: clusters of osteoclast-type multinucleated giant cells concentrated around areas of hemorrhage, set in a stroma of ovoid-to-spindled mononuclear cells with proliferating fibrovascular tissue and hemosiderin deposition. Poorly mineralized woven bone may be present at the margins.[1][4][7]
• Radiologic–pathologic correlation: the vascular, hemorrhagic stroma accounts for the lytic expansile appearance and the brown gross color; sites of healing after treatment show new bone formation corresponding to radiographic sclerosis.[1][8]
• Diagnostic limitation: the picture is essentially identical to central giant cell granuloma and overlapping with aneurysmal bone cyst and giant cell tumor of bone, so histology cannot render a stand-alone diagnosis—serum calcium and PTH are required to confirm a brown tumor.[1][14]
• Molecular findings: activating KRAS mutations have been identified in jaw brown tumors, placing them—together with the giant cell granulomas that carry KRAS, TRPV4, and FGFR1 alterations—within the RAS-MAPK–driven spectrum and challenging the view that they are purely reactive. These findings refine classification but do not currently alter routine management.[2][4]

• Treat the hyperparathyroidism first. In secondary disease this is medical management of CKD-mineral and bone disorder: dietary phosphate restriction and phosphate binders, active vitamin D/analogues, and calcimimetics for inadequately controlled PTH, in line with CKD-MBD guidance. Control of PTH and the calcium–phosphate product typically leads brown tumors to regress and ossify without direct intervention.[5][8][11][17][18]
• Parathyroidectomy is indicated for severe or refractory secondary hyperparathyroidism and can drive rapid healing of the bone lesion; it is the preferred route when regression of tumor bulk is urgently needed.[1][8]
• Local surgery of the jaw lesion (curettage/osteoplasty or, rarely, resection) is reserved for large, symptomatic, or functionally compromising lesions that do not respond adequately to control of the endocrine disease, or that threaten structural integrity. There is no validated scoring system to select lesions for prophylactic surgery.[1][5]
• Workup and referral: confirm serum calcium, phosphate, and intact PTH, assess renal function, and coordinate care across nephrology, endocrinology, oral and maxillofacial surgery, and pathology; biopsy for giant-cell morphology is interpreted only alongside the biochemistry.[1][5]
• Recurrence and surveillance: lesions that persist usually reflect inadequately controlled PTH; serial imaging documents progressive infilling, with bone regeneration at the tumor site reported on average around seven months after successful parathyroid treatment.[5][8]
• Outcome is generally favorable once the metabolic driver is controlled; the main threats are misdiagnosis as malignancy and the systemic cardiovascular and skeletal morbidity of uncontrolled secondary hyperparathyroidism.[1][11]

Post-parathyroidectomy hungry bone syndrome

After correction of long-standing severe hyperparathyroidism, rapid skeletal re-uptake of calcium can precipitate profound hypocalcemia (hungry bone syndrome), warranting anticipatory calcium and vitamin D repletion and close monitoring in the perioperative period.[19]

Generalized renal osteodystrophy of the jaws

In advanced CKD the jaws may show diffuse bilateral expansion with a generalized ground-glass pattern and lost lamina dura, so an isolated brown tumor should be read within this broader high-turnover context rather than as a solitary tumor; recognizing the systemic picture guides treatment toward metabolic control.[9][12]