Osteoid osteoma is a bone-forming neoplasm defined by the presence of a small, radiographically lucent central region of fibro-osseous tumor, surrounded by a zone of reactive bone sclerosis, referred to as a nidus (Figure 1). A unique feature of this lesion is the clinical presentation of localized pain, often easily identified by the patient, with a characteristic pain pattern that is often described as a deep, aching pain comparable to a severe toothache. This pain is often rapidly alleviated temporarily by administration of aspirin or other NSAIDs. Patients frequently present with months to years of pain before their actual diagnosis. This pain, which should be easily distinguished from mechanical symptoms based on the presence of pain at rest and at night, can be so severe that some patients may self-medicate with toxic doses of over-the-counter NSAIDs in an attempt to minimize their symptoms. The ability of aspirin and NSAIDs to alleviate pain from an osteoid osteoma is due to the well-documented production of prostaglandin E2 and prostacyclin by the lesion, which is blocked via inhibition of cyclo-oxygenase enzymes (COX-1 and COX-2) by these medications. Rapid short-term relief after a dose of aspirin can be used as a clinical test for these lesions.

The production of prostaglandins results in an inflammatory cascade affecting the surrounding structures. Osteoid osteomas that occur adjacent to or within joints frequently present with symptoms of joint effusion and stiffness mimicking monoarticular inflammatory arthritis (Figure 2). When lesions occur along the spine, a reactive scoliosis may be present. Although most patients can often precisely localize the source of their pain, lesions that arise adjacent to a peripheral nerve or nerve root may result in diffuse referred or radicular pain, making localization difficult.

Osteoid osteomas comprise 10% to 12% of all benign bone tumors, rendering it the third most common benign bone tumor, with a peak incidence in the second decade of life. Although more than 80% of lesions occur between the ages of 5 and 30 years, rare cases have been observed in patients as young as 2.5 years. Males are more commonly affected, with a sex ratio of 3:1. Although these lesions can occur in any bone, most occur in long bones of the lower extremity (eg, femur and tibia), followed by the upper extremity and posterior elements of the spine. Lesions can be classified by their location within the bone, such as along the endosteal or periosteal surfaces of the bone or contained inside the cortex itself. Although these lesions are solitary, the presence of a second nidus may rarely be noted and can occasionally present after the treatment of the original lesion, mimicking a local recurrence. As described in a 2021 study, the detection of intracellular viral particles combined with the small size and self-limited nature of some of these lesions suggest an inflammatory origin for these neoplasms.¹

The appearance of a nidus on plain radiographs, consisting of a central lucency surrounded by a sclerotic rim of bone, is highly suggestive of an osteoid osteoma. The amount of surrounding bone can be influenced by the physical location of the nidus within the bone. Because of the small size of these lesions, high-resolution CT may be necessary to visualize the actual nidus and its relationship to the surrounding bone (Figure 3). Frequently, significant amounts of reactive cortical bone may be seen surrounding the nidus (Figure 4). MRI may demonstrate substantial amounts of edema in the adjacent bone and soft tissue, which is a response to the inflammatory action of prostaglandin production (Figure 5). Evaluation with MRI in the absence of radiography or CT may result in misdiagnosis of this condition. A 2020 study states that use of dynamic postcontrast imaging may help improve detection of the nidus via MRI.² Bone scan is extremely sensitive to the presence of these lesions and can help localize a nidus (Figure 6) and/or help establish the presence of multifocal involvement in patients in whom the referred pain may obscure the location. Positron emission tomography (PET) of osteoid osteomas is characterized by intense focal hypermetabolic activity that has been shown to resolve rapidly following radiofrequency ablation (RFA).

The central radiolucent portion of the nidus, which rarely measures more than 1.0 to 1.5 cm in diameter, is filled with a red, relatively soft and friable tissue that is easily separated from the surrounding sclerotic bone (Figure 7). Microscopically, the nidus is characterized by an interlacing network of osteoblast-lined trabeculae (Figure 8, A). Calcification of the osteoid may be prominent, particularly in the center, and cement lines are common. Scattered multinucleated giant cells are often noted. The intertrabecular stroma consists of a richly vascular connective tissue, devoid of hematopoietic elements (Figure 8, B). Electron microscopy with axonal silver stain has been used to demonstrate the presence of nerve endings within the nidus. The hypertrophic bone surrounding the nidus usually reveals nonspecific sclerotic changes.

Radiographically, an osteoid osteoma must be distinguished from a stress fracture or Brodie abscess, both of which are common in this age group. There may be overlap in the appearance of a large osteoid osteoma and a small osteoblastoma. The presence or absence of the typical pain pattern seen with osteoid osteoma as well as the response to aspirin or other NSAIDs helps differentiate these entities. The radiographic differential also includes osteomyelitis, bone island of the medullary canal, intracortical hemangioma, bone abscess, intracortical osteosarcoma for cortically based lesions, and early Ewing sarcoma. Clinically, osteoid osteomas can mimic many other inflammatory conditions, such as monoarticular arthritis or radiculopathy, with symptoms determined by the anatomic location of the nidus, as mentioned in a 2023 study.³

Osteoblastoma, a rare fibro-osseous tumor arising from bone, was described in 1956 as a lesion related to osteoid osteoma but characterized by greater growth potential. A more aggressive form, termed aggressive osteoblastoma, was described in 1973 with histologic and radiographic features overlapping osteosarcoma of bone. Given this range of histologic features, it remains an open question as to whether osteoblastoma can transform into malignancy, as suggested in a 2020 study.⁷ Osteoblastoma is differentiated from osteoid osteoma by size (>1.5 cm) and although occasionally painful it is without the classic pain pattern associated with osteoid osteoma. When present in the jaw along the roots of the teeth, it is often referred to as a cementoblastoma. Secondary aneurysmal bone cyst (ABC) formation arising in an area of osteoblastoma may occur, leading to rapid enlargement and bone destruction that can mimic a malignancy. Osteoblastoma must be differentiated from osteosarcoma and osteoid osteoma. Clinical correlation of age, location, size, and histologic findings lead to the correct diagnosis. A recently described variant, epithelioid multinodular osteoblastoma, features multiple nidi within a single lesion and appears to have a benign prognosis.

Osteoblastoma are much rarer than osteoid osteomas and account for fewer than 1% of all bone tumors, with a peak incidence in the second decade of life. Most patients are between the ages 5 and 45 years, a slightly older cohort than that seen with osteoid osteoma, while a similar male/female ratio of 3:1 is seen. Of interest is that the osteoblastoma has a predilection for the axial skeleton, with more than 50% of cases involving the posterior elements of the vertebral column, sacrum, and skull. Lesions occurring in the appendicular skeleton mirror the distribution seen with osteoid osteoma. Unlike osteoid osteomas, which frequently involve the cortex, osteoblastomas typically involve cancellous bone. Extraosseous lesions have occasionally been reported, as discussed in a 2020 study.⁸

The classic radiographic appearance of an osteoblastoma is similar to that of an osteoid osteoma, with a central, well-defined lytic region surrounded by sclerotic, reactive border of bone (Figure 11). Unlike osteoid osteomas, the lytic area exceeds 1.5 to 2 cm in size, which is often used as a distinguishing feature between the two lesions. Lesions involving the spine predominantly involve the posterior elements of the neural arch (Figure 12), resulting in thinning and occasional destructive expansion of the bone, particularly when secondary ABC formation occurs (Figure 13). Aggressive osteoblastomas have a similar radiographic appearance, but typically exceed 4 cm in diameter, with some documented cases reaching 10 cm in size. Depending on the location, cortical destruction and resultant periosteal reaction that mimic osteosarcoma may be present. Plain radiographs and axial CT scans that demonstrate the presence of osteoid matrix and the relationship of the lesion to the surrounding bone are best suited for the diagnostic workup of a suspected osteoblastoma (Figure 14). MRI may be misleading due to the inflammatory response often seen with osteoblastoma, which can suggest a more aggressive or malignant lesion.