Osteoblastoma

                                     Dr. KS Dhillon

Introduction

Osteoblastoma is an uncommon benign bone-forming neoplasm. It accounts for about 1% of all primary bone tumors, 10% of all osseous spinal neoplasms, and 1 to 5 % of all benign bone tumors [1-3]. There are histopathologic similarities to an osteoid osteoma and hence, historically, it was referred to as giant osteoid osteoma [4].

There are some authors who consider these two entities to be variant expressions of the same pathologic process. The prevailing opinion, however, is that they are distinct pathologic entities with varying clinical presentations.

Osteoblastoma usually arises in the posterior elements of the spine and the sacrum (about 30 to 40%) [5]. Other common locations include the mandible and long tubular bones, where it is usually seen in the metadiaphysis [4]. An accurate diagnosis of osteoblastoma is important before appropriate treatment can be given and prognosis determined [6]. 

The diagnosis is usually made from clinical, radiological, and histopathological examination. The radiological appearance of the osteoblastoma is variable ranging from indolent to very aggressive [7].

The prognosis is usually good in patients with osteoblastoma. Patients are usually cancer-free after surgical treatment with intralesional curettage or marginal en bloc resection [8]. In patients with osteoblastoma that is not amenable to surgical excision, radiotherapy can be given. There are 2 borderline osteoblastic tumors i.e aggressive (epitheliod) osteoblastoma or osteoblastoma-like osteosarcoma, that must be differentiated from osteoblastoma with more aggressive presentation [9]. Occasionally osteoblastoma can be associated with systemic symptoms such as weight loss, fever, and diffuse periostitis, referred to as toxic osteoblastoma [10].

Etiology

The exact etiology of osteoblastoma is not known. FOS expression has been reported in osteoblastomas, and this suggests that fluorescence in-situ hybridization analysis for FOS rearrangement could be helpful in cases with worrying histologic features [11].

Epidemiology

Osteoblastoma is an uncommon benign bone-forming neoplasm. It accounts for about 1% of all primary bone tumors, 10% of all osseous spinal neoplasms, and 1 to 5 % of all benign bone tumors [1-3]. It mainly affects adolescents and young adults with a mean age of 20 years. There is a male predominance of 2.5 to 1. The more aggressive forms are usually seen in slightly older patients, with a mean age of 33 years [3,12]. Osteoblastomas can involve any bone. It, however, has a predilection for the spine and the sacrum (40 to 55%). It most commonly involves the posterior elements of the spine [13]. Other common sites include the facial bones and the long bones with a predilection for the lower extremity [4]. 

Less commonly it involves the tarsal bones (talus and calcaneum). There are case reports of involvement of the carpal bones and phalanges [14,15]. The bone location of the osteoblastoma can be cortical, medullary, or rarely periosteal [16].

Pathophysiology

Just like osteoid osteomas, osteoblastoma demonstrates marked new bone formation. This process is generally more exuberant in osteoblastoma, and the lesions tend to be more vascularized [17].

The nidus within osteoblastoma has less organized osteoid and trabecular bone, less abundant nerve fibers, and lacks prostaglandins as seen in osteoid osteomas [8,18]. Osteoblastomas often cause significant bone destruction, infiltration of the soft tissues, and epidural extension. They often show aggressive behavior with uncontrollable local recurrence. Malignant transformation, as well as metastatic diseases, have been reported with osteoblastoma [3,19].

The lack of prostaglandin production accounts for the variation in clinical presentation between osteoid osteoma and osteoblastoma, especially the nighttime pain that is relieved by salicylates, which is seen in patients with osteoid osteoma. Patients with osteoblastoma are usually asymptomatic or have dull, localized pain, which rarely interferes with sleep [20,21]. Both osteoblastoma and osteoid osteoma express Osterix and Runx2 transcription factors involved in osteoblastic differentiation [22].

Clinical presentation

Osteoblastomas grow slowly with minimal or no symptoms. The lesions are usually found incidentally during imaging for other diseases. Patients with osteoid osteoma are slightly younger and they have night-time pain that is relieved by salicylates [20,23]. 

Sometimes patients with osteoblastoma are symptomatic and they present with dull, localized pain. In some patients, the lesions are tender on palpation and present with soft tissue swelling [20]. 

Osteoblastomas of the spine can present with back pain, scoliosis, and nerve root compression [23,24]. Nerve root compression can lead to muscle weakness or paraplegia [25]. Toxic osteoblastoma is a rare variant of osteoblastoma. It can be associated with systemic symptoms, including fever, weight loss, anorexia, and diffuse periostitis [26]. 

Osteoblastomas usually do not extend into the surrounding soft tissues and generally do not produce soft tissue edema or inflammatory response. The prognosis is generally favorable, although local recurrence has been reported in about 25% of the cases [27]. There have been rare case reports of malignant degeneration over the years. Recent genomic studies, however, contradict these reports [28,29].

Evaluation

Modalities that are available for establishing the diagnosis of osteoblastoma include:

• Plain radiographs

• Computed tomography (CT)

• Magnetic resonance imaging (MRI)

It can be difficult on imaging to distinguish an osteoblastoma from an osteoid osteoma [7]. The lesions are usually radiolucent, round to oval, with well-defined margins, and with reactive sclerosis [3]. The imaging appearance may vary with the patient’s age and lesion maturity. The lesions are more often radiolucent in young patients and have increased sclerosis/ossification in older patients. There is thinning of the cortex but destruction or disruption of the cortex is only rarely seen in about 20% of cases [3]. In patients with disruption of the cortex, the lesions can be mistaken for a malignant process. Benign periosteal reaction is common and is seen in up to 86% of cases [3]. Generally, the lesions in the spine, pelvis, and talus demonstrate less surrounding reactive bone formation as compared to lesions of the long bones [21].

Radiographs (X-ray)

Plain film radiography is generally used for the diagnosis of osteoblastoma (fig 1). The radiographic appearance can vary slightly. Four distinctive radiographic presentations have been described [3,21]. 

1. A radiographic appearance similar to an osteoid osteoma but larger in size (>2 cm), with less reactive surrounding sclerosis and more overlying periostitis.

2. A blown-out expansile lesion mimicking an aneurysmal bone cyst. This pattern is most commonly seen in lesions of the axial skeleton [30].

3. Aggressive appearing lesions that mimick a malignant process with cortical expansion, thinning, or disruption, as well as extensive periostitis and large size (often greater than 4 cm). Aggressive osteoblastomas generally fall into this category. Some authors believe that aggressive osteoblastomas are a distinct entity as opposed to a subtype of osteoblastoma [9][31].

4. Juxtacorticl or periosteal lesions are exceedingly rare, comprising 8 of 62 osteoblastoma cases in the literature [12,32]. These lesions have a thin periosteal margin but lack the exuberant surrounding sclerosis that is seen in most lesions [18].

Fig 1

Computed Tomography Scan

CT imaging has a complementary role to plain-film radiography in the diagnosis of osteoblastoma. The imaging appearance is similar to those described for radiography. The CT scan can help further characterize the lesions, specifically the size, exact location, presence, or extent of cortical disruption and the presence of a soft tissue component [33]. A CT scan is also useful for characterizing lesions present in locations that are suboptimally evaluated on radiographs due to overlapping/superimposed structures, such as lesions in the spine or pelvis [23].

Magnetic Resonance Imaging

MRI can characterize the extent of the lesion and the presence of aggressive imaging features. The contrast resolution on MRI allows for identifying reactive soft tissue edema and better evaluates the soft tissue component if present. Perilesional edema and extension into the surrounding soft tissues are rare with osteoblastoma. 

Nuclear Medicine Imaging 

Nuclear medicine imaging is generally not employed to evaluate osteoblastomas. Studies using technetium-99m will demonstrate increased uptake in the mass corresponding to the osteoid formation within the lesion. FDG-PET studies have revealed a high uptake in the tumor despite its pathologically benign features [34].

Treatment 

Osteoblastomas are treated by surgery. Surgery involves either en bloc resection or curettage, depending on the clinical situation, location within the bone, and suspicion of malignancy [35,36]. En-bloc resection is the preferred treatment whenever it is possible. En-bloc resection results in a lower risk of local recurrence than curettage. Recurrence rates as high as 25% have been reported. Multiple episodes of local recurrence are known to occur. There is no definite role for adjuvant radiotherapy or chemotherapy [27,37]. 

Sometimes imaging surveillance is necessary due to the risk of local recurrence. There are case reports in the literature on malignant degeneration. However, recent genomic studies contradict these findings [26,27].

Differential Diagnosis

The histological differential diagnosis of osteoblastomas includes:

• Osteoid osteoma

• Aneurysmal bone cyst

• Osteoma with osteoblastoma-like features

• Osteoblastoma-like osteosarcoma [38]

• Giant cell tumor of bone

The radiological differential diagnosis includes:

• Osteoid osteoma

• Osteosarcoma

• Aneurysmal bone cyst

• Infection (Brodie abscess)

• Metastasis [7]

Osteoid Osteoma

Osteoid osteoma and osteoblastoma can have a similar appearance in imaging studies and histology. Osteoid osteoma is more common in the appendicular skeleton whereas osteoblastoma commonly involves the spine and craniofacial structures specifically the mandible. Both can present with pain. Osteoblastoma is usually asymptomatic or only mildly symptomatic. Unlike osteoid osteoma, the pain due to osteoblastoma is not relieved by salicylates and is not disruptive to sleep. Osteoid osteomas can resolve/regress spontaneously and, therefore, in some cases, are treated symptomatically, while others are treated with percutaneous radiofrequency ablation. Osteoblastoma does not resolve/regress and degeneration into osteosarcoma has been reported, although this has been disputed [29,39]. 

Osteoblastomas are usually greater than 2 cm in size, while osteoid osteomas are smaller lesions. There can be subtle differences in the nidus' appearance, which may allow for distinguishing osteoid osteoma from osteoblastoma. The nidus of osteoid osteoma is more organized with a thin peripheral fibrovascular rim and a zonal pattern with central mineralization. On the other hand, osteoblastomas generally lack the fibrovascular rim and exhibit a lobulated or multifocal appearance [8,40].

Aneurysmal Bone Cyst

About 81% of aneurysmal bone cysts (ABC) occur as a primary benign osseous lesion. ABCs can secondarily arise from preexisting lesions such as osteoblastoma, giant cell tumor, chondroblastoma, and fibrous dysplasia. The radiographic appearance is that of an eccentric medullary-based, expansile, lucent lesion which has a thin cortex and well-defined, thin sclerotic margins. ABCs usually occur in the metaphysis of long bones (50 to 60%) but can also occur in the spine and sacrum (20 to 30%), predominately in the posterior elements. In 12 to 18% of the cases, the lesions can be cortically located, and in 7 to 8% of the cases, it can be located periosteally [41,42]. 

Cross-sectional imaging (CT and MRI) usually shows fluid-fluid levels and internal septations. Histopathology will show multiple blood-filled sinusoidal spaces with fibrous septations/walls, which may contain osteoid tissue, hemosiderin or reactive foam cells, and mature bone collections. There may also be richly vascularized solid components containing numerous giant cells [43]. ABCs are usually treated with curettage and bone grafting.

Giant Cell Tumor

Giant cell tumors are common benign osseous neoplasms. Eighteen to twenty percent of benign osseous tumors are giant cell tumours. They involve the metaphysis of long bones and extend to the epiphysis. They are often close to the articular surface with well-defined margins without significant surrounding sclerosis.

There is a female predilection of 3 to 1 and the peak incidence is between 20 to 30 years of age [44]. These features are different from that of osteoblastomas which have a male predominance, a peak incidence in the second decade, diaphyseal-metaphyseal location, and sclerotic margins with reactive periostitis. Periostitis can be seen in patients with giant cell tumors if there is an associated pathologic fracture. Microscopically giant cell tumors have giant cells evenly distributed throughout spindle cell stromal tissue. Rarely there is small amounts of osteoid formation [45].

Infection (Brodie abscess)

Brodie abscess is a subacute or chronic form of osteomyelitis. It usually occurs in pediatric patients prior to the closure of the growth plate. It can, however, occur in patients of any age. It presents as a radiolucent lesion, in the metaphysis of tubular bones. It is most often seen in the tibia. There is a 2 to 1 male predilection.

Patients usually present with pain and/or swelling. Most of the patients are afebrile, and less than half have elevated inflammatory markers. X-rays in skeletally immature patients will show a serpentine tract extending to the closest physis, periostitis, and adjacent soft tissue swelling with sclerotic margins. The penumbra sign, a rim of T1 hyperintense signal lining the abscess, is a distinguishing imaging feature on MRI.

Osteoblastoma-like osteosarcoma and Aggressive Osteoblastoma

These lesions represent unique borderline entities. They are not subtypes of osteoblastoma. These borderline lesions are exceedingly rare. An open biopsy instead of a percutaneous image-guided biopsy is necessary to establish the diagnosis.  In one study, only 36% of osteoblastoma-like osteosarcoma lesions demonstrated aggressive imaging features. 

Osteosarcoma

There are several subtypes of osteosarcomas with varied imaging and clinical presentations. Generally, osteosarcomas have a more aggressive appearance than osteoblastoma. The aggressiveness of the lesion is first characterized by radiographic imaging. Non-aggressive lesions have a well-defined narrow zone of transition with or without a sclerotic margin. Aggressive lesions will have incomplete or poorly defined margins with a wide zone of transition. Osteosarcomas will present with aggressive forms of periostitis, such as an "onion-skin or sunburst" appearance. Telangiectatic osteosarcoma, like conventional osteosarcoma, will have a more aggressive appearance than most osteoblastomas. Telangiectatic osteosarcoma will present as an expansile, lucent lesion with thin septations. An open biopsy may be needed to make an appropriate diagnosis.

Prognosis

The prognosis of osteoblastoma is excellent. Most patients are cured following the initial surgical treatment. Local recurrence is a relatively common complication, with rates ranging from 15% to 25% [13]. 

Recurrence is more common when the osteoblastoma is treated with curettage. Spinal lesions are often treated with curettage due to the anatomic challenges and morbidity of performing wide local excision. Hence, the high recurrence rates have been associated with spinal lesions. Recurrence is usually common in the first 2 years following treatment. After 2 years post-treatment recurrence is rare. Long-term follow-up imaging and clinical surveillance are necessary for at least 2 years to detect recurrence [37]. Degeneration into osteosarcoma has been reported in the literature, but recent genomic studies contradict these findings [3,38]. 

Complications

The most frequently encountered postoperative complications following surgical removal of osteoblastoma are:

• Wound infections

• A loss of stability involving the surgical stabilization construct

• Surgical site hemorrhage 

Tumor recurrence typically occurs late (i.e. months to years) after the surgery. There are no universally accepted time intervals to define this period.

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