Pseudotumors and tumorlike lesions of bone can be mistaken for malignant bone tumors, metastatic bone disease, multiple myeloma, lymphoma, or benign aggressive bone lesions, such as giant cell tumor. The overlap of symptoms and imaging findings necessitates appropriate history, physical examination, imaging, laboratory studies, and when appropriate, a biopsy. The key distinguishing features of the most common pseudotumors of bone, including osteomyelitis, osteonecrosis, Paget disease of bone, sarcoidosis, enostoses, hyperparathyroidism, and cortical desmoids, are reviewed.

Osteomyelitis is one of the most common mimickers of malignant bone tumors, leading to the adage “Biopsy what you culture, and culture what you biopsy.” There are similarities in clinical presentation (eg, fever, pain, swelling, decreased range of motion) and imaging characteristics between osteomyelitis and malignant bone tumors (eg, osteolysis, periosteal reaction, soft-tissue mass), making the diagnosis of these two disease processes challenging.

As described in two recent studies, acute osteomyelitis in adults results from direct contamination from adjacent soft-tissue infection or trauma.^1,2 In contrast, acute osteomyelitis in children (diagnosed within 4 weeks after the onset of symptoms) is often caused by hematogenous spread and has an incidence of approximately 1.2 to 13 cases per 100,000 children in the United States.^2,3 During skeletal maturation, changes in vascularity to different regions of the bone account for the higher rate of acute hematogenous osteomyelitis in patients younger than 20 years.^2,4

In addition to imaging, diagnosis of osteomyelitis includes laboratory studies, blood cultures, and local tissue cultures. Radiographs of the affected bone may be unremarkable in the early stages of osteomyelitis.⁴ Over time, osteolysis, periosteal reaction, cortical irregularity (either erosion or expansion), and a lesion with a wide zone of transition often develop. A soft-tissue mass may be present if there is an associated subperiosteal or soft-tissue abscess (Figure 1). MRI is the advanced imaging modality with the highest diagnostic accuracy and is preferable to ultrasonography, bone scintigraphy, and CT.^1,3,5 Treatment of osteomyelitis includes culture-directed antibiotics and often requires surgical intervention, specifically in children, in patients with subperiosteal and soft-tissue abscesses, and to remove any sequestrum.^3,4

Chronic recurrent multifocal osteomyelitis (CRMO) is a nonbacterial, autoimmune, inflammatory disease process. Patients report bone pain, nighttime pain, and swelling; however, constitutional symptoms such as fever or fatigue are not as frequently reported. Because of the insidious nature of this disease, radiographic changes of the involved bone can simulate oncologic diagnoses as a result of osteolysis and periosteal reaction, as discussed in two 2023 studies.^6,7 MRI frequently demonstrates nonspecific bone marrow edema, and when CRMO is suspected, whole-body MRI is recommended, rather than focused MRI of one bone.^6,7 The diagnosis and treatment of CRMO is evolving, but once malignant conditions have been excluded, CRMO is often treated with NSAIDs.⁷

Causes of bone infarcts are numerous and include chronic steroid use, autoimmune disorders (eg, systemic lupus erythematosus), diabetes, coagulopathies, sickle cell disease, radiation exposure, chronic renal failure, trauma, alcoholism, hematologic malignancies (eg, lymphoma, leukemia), and cancer treatments, or may be idiopathic.^8,9,10 Patients may present with pain, limited range of motion, and swelling. Bilateral, symmetric-appearing bone infarcts are not uncommon.⁵

Early imaging findings of osteonecrosis on radiographs may be subtle or nonexistent. Over time, osteonecrosis appears as a geographic region with central lucency and a sclerotic border, which is often described as serpiginous^5,8,10 (Figure 2). MRI of osteonecrosis may show nonspecific bone marrow edema initially, followed by development of the sclerotic bone at the periphery of the lesion.⁸ Imaging findings of osteonecrosis may overlap with chondroid-containing bone lesions, with arc-and-ring calcifications. The key distinction is the sclerotic border in osteonecrosis, as opposed to chondroid-containing bone lesions.⁸ In addition, on MRI, the double-line sign (parallel bands of high and low T2 signal) is considered pathognomonic for osteonecrosis⁵ (Figure 3).

Treatment of osteonecrosis depends on the location, severity, and cause. Interventions range from managing symptoms with various medications (over-the-counter pain medications, bisphosphonates (also known as diphosphonates), injections) to surgical interventions (core decompression, free vascularized fibular grafts, and arthroplasty).^9,10