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A 13-year-old adolescent boy presented with painful scoliosis. He had reported relapsing/remitting back pain during the previous 2 years, and progressive scoliosis was detected on serial physical examinations. Computed tomography (CT) scan of the spine revealed a 2.2-cm, expansile, osteolytic and osteosclerotic bone tumor centered within the pedicle of T7 (Figure 1). After core biopsy it was excised. Grossly, the tumor was gritty to hard, expansile but well-marginated, and had a central sclerotic nidus surrounded by trabecular bone and by a peripheral rind of sclerotic bone. Microscopically, it had typical features of osteoblastoma (Figure 2). At last follow-up, 18 months postoperatively, the patient continues to have intermittent back pain. However, there is no evidence of recurrent tumor by imaging.


Osteoblastoma is rare, accounting for only 1% of primary bone tumors. It has a wide age range (6-75 years). However, it most commonly affects adolescents and young adults (mean age, 20 years). (1) Virtually any bone can be involved, with spine and sacrum accounting for one-third of cases (Figure 3). Progressive pain is the most common symptom. However, it usually does not have the intense pain pattern that awakens one at night, as does osteoid osteoma. Spinal osteoblastoma presents with neurologic findings and often with progressive scoliosis, as in this case. In general, osteoblastoma has a good prognosis with a local recurrence rate of about 15% to 20%, (1) and most recurrent tumors can be successfully treated by reexcision. Tumors located near the central neural axis tend to have a worse prognosis probably owing to difficulty in achieving complete excision. Only very rare examples of osteoblastoma progressing to osteosarcoma have been reported. (1)

Radiographic Features

The radiographic appearance of osteoblastoma is variable, often nonspecific, and can mimic other tumors, including malignant ones. (2) Most often, however, the appearance is benign and the diagnosis can at least be suggested from the radiographs. For example, many tumors show intratumoral ossification, including some with a central nidus of sclerotic bone surrounded by a radiolucent halo similar to osteoid osteoma (Figure 1). Most osteoblastomas are sharply marginated and have a peripheral rind of sclerotic bone (Figure 4). Some tumors are very expansile, similar to aneurysmal bone cyst (Figure 5). Most tumors remain confined to bone and do not destroy or penetrate cortex. However, up to 25% have features that can mimic a malignant bone tumor, (2) such as large size or destructive growth (Figure 6). Spinal osteoblastoma has a high tendency to affect the dorsal elements (lamina, pedicle, or spinous process) as opposed to the vertebral body. For example, 55% are limited to dorsal elements and 42% involve dorsal elements and body, while only 3% involve the body alone. (1)


Because most osteoblastomas are treated by curettage, the gross specimen usually consists of fragments of red gritty tissue. Within an intact specimen, osteoblastoma is usually sharply demarcated from adjacent bone, often with a scalloped edge, and is often surrounded by a rim of sclerotic host bone. Expansile tumors may be encased by a thin shell of cortical bone. Some tumors have a central sclerotic nidus similar to osteoid osteoma (Figure 7). Some are very hemorrhagic with cystic areas of hemorrhage or loculated secondary aneurysmal bone cyst changes. The average size is 3 to 3.5 cm, but osteoblastoma can be quite sizeable, up to 15 cm. (1)

Microscopically, osteoblastoma is composed of interanastomosing trabeculae of woven bone, set within loose edematous fibrovascular stroma (Figure 2). It may or may not have a central sclerotic nidus (Figure 8). Most tumors show a spectrum of bony maturational changes ranging from cords and clusters of activated osteoblasts associated with minimal osteoid (Figure 9, A) to lacelike wispy osteoid (Figure 9, B) to broad anastomosing trabeculae of woven bone (Figure 9, C) to sclerotic sheets of woven bone (Figure 9, D). As a rule, the osseous trabeculae are lined by a single layer of osteoblasts. Because osteoblastoma undergoes continuous remodeling, osteoclastic giant cells are usually in abundance. Howship lacunae and pagetoid remodeling changes with numerous reversal lines (Figure 9, D) attest to ongoing remodeling. The bony trabeculae connect with the peripheral bony edge of the tumor (Figure 10). Osteoblastoma does not permeate adjacent bone or invade soft tissue.



The cytologic features of osteoblasts are variable. Large immature osteoblasts have abundant, eccentric, basophilic, finely granular cytoplasm; perinuclear hof consistent with Golgi apparatus; and large vesicular nucleus with a prominent nucleolus (Figure 11). Mature osteoblasts are smaller with less cytoplasm and smaller nuclei, while mature osteocytes are smaller yet and contained within the bony matrix. Mitotic activity is low and atypical mitotic figures are not seen. Osteoclasts vary from polygonal cells with only a few nuclei to large multinucleated giant cells with dozens of nuclei.


Other microscopic findings present in some osteoblastomas include heavily calcified immature bone or "spiculated blue bone" (Figure 12), prominent spindle cell fibrovascular stroma (Figure 13), and extensive intralesional hemorrhage (Figure 14), including tumors with secondary aneurysmal bone cyst changes. Rarely, one finds cartilage or chondro-osseous matrix within an osteoblastoma3 (Figure 15) in the absence of fracture, a finding once believed to be more in keeping with osteosarcoma. Degenerative cytologic atypia is characterized by cells with large degenerated nuclei and smudged chromatin mimicking a malignant tumor (Figure 16). This finding is similar to that seen in ancient schwannoma. Osteoblastomas with extensive degenerative atypia are termed pseudomalignant osteoblastomas. (4) Multifocal (or multinodular) osteoblastoma defines a subset of tumors with multiple nidi or growth centers within a single tumor, separated by reactive bone or spindle cell stroma (Figure 17). These tumors frequently contain epithelioid osteoblasts. (5)












Osteoblastoma frequently occurs in the jaws, mandible more often than maxilla. It is often associated with the root of a tooth where it forms an ossified, well-demarcated tumor (Figure 18). Tooth root tumors are also referred to as cementoblastomas. Microscopically, the bony matrix tends to be abundant in these tumors and to radiate from the tooth root in parallel arrays (Figure 19).

The term aggressive osteoblastoma was introduced in 1984 by Dorfman and Weiss. (6) This rare entity is purported to have clinicopathologic features that set it apart from conventional osteoblastoma, although not all investigators have been able to validate this conclusion. (1,7) Aggressive osteoblastoma is characterized by locally aggressive but nonmetastasizing behavior and distinctive histologic features. It comprises large epithelioid osteoblasts, defined as cells with abundant eosinophilic cytoplasm twice the size of conventional osteoblasts (Figure 20). They either rim the osteoid as in conventional osteoblastoma or arrange themselves in sheets and clusters devoid of matrix. Differentiating aggressive osteoblastoma from epithelioid osteosarcoma can be challenging. Certainly, aggressive behavior is within the spectrum of osteoblastoma, whether or not it has a prominent epithelioid osteoblastic morphology. (1,7) For example, tumors near the spinal cord and skull base can cause considerable morbidity and even mortality because of a limitation to surgical extirpation by anatomic constraints.







Differential Diagnosis

Osteoid Osteoma.--Distinguishing osteoblastoma from osteoid osteoma is somewhat arbitrary. In fact, many authors believe they represent members of a spectrum of neoplasia. For example, many osteoblastomas have the architectural configuration of an osteoid osteoma consisting of a central ossified nidus surrounded by trabecular woven bone. In fact, an early designation for osteoblastoma was "giant osteoid osteoma." (8) In general any tumor larger that 1.5 cm is called osteoblastoma, while anything less than that is an osteoid osteoma. Osteoid osteoma, however, differs clinically from osteoblastoma in that it is more painful (worse at night, relieved by analgesics) and less likely to progress.

Aneurysmal Bone Cyst.--Because osteoblastoma can be very hemorrhagic and show secondary aneurysmal bone cyst changes, and conversely, because primary aneurysmal bone cyst can show extensive reactive new bone production that resembles osteoblastoma, it can be challenging to tell them apart in some cases. In general, however, in osteoblastoma with secondary aneurysmal bone cyst change, one can usually find a sizeable intact focus of tumor seemingly independent of the cystic changes. Distinguishing osteoblastoma from aneurysmal bone cyst can be especially challenging in spinal tumors since both tend to form expansile tumors originating from the dorsal vertebral elements. Fortunately, this distinction has little clinical relevance, since they are treated and behave in a similar manner.

Giant Cell Tumor of Bone.--Osteoblastoma and giant cell tumor of bone are usually easy to distinguish. Giant cell tumor is composed of sheets of mononuclear histiocytoid stromal cells admixed with numerous, evenly dispersed osteoclastic giant cells. Clinically, giant cell tumor also differs from osteoblastoma. For example, in long bone it involves the epiphysis and in the spine it involves the vertebral body, both of which are uncommon locations for osteoblastoma, which tends be metaphyseal in long bone and to involve the neural arch of a vertebra. Giant cell tumor, however, can show a variety of secondary histologic changes including osteoid and woven bone formation and secondary aneurysmal bone cyst changes that mimic osteoblastoma. Occasionally, giant cell tumor produces a large amount of collagenous matrix that forms interanastomosing trabeculae of osteoid-like matrix that mimics osteoblastoma.

Osteoma With Osteoblastoma-like Features.--Although osteoblastoma occurs in the maxilla and calvarium, it is very rare in the paranasal sinuses, nasal cavity, and orbit. By contrast, osteoma commonly affects these anatomic sites and is the most common tumor of the paranasal sinuses. (9) Sino-orbital osteoma typically forms a solid bony mass that produces a sessile polypoid growth within a sinonasal cavitary space or within the orbit. It is composed primarily of mature compact or trabecular bone. However, nearly 40% have foci of immature woven bone within loose fibrovascular stroma indistinguishable from osteoblastoma. (10) Although believed by some to have a more aggressive behavior, osteoma with osteoblastoma-like features has the same behavior as conventional sino-orbital osteoma. (10) Distinguishing this tumor from osteoblastoma often requires clinicopathologic and radiographic correlation.

Osteoblastoma-like Osteosarcoma.--Osteosarcoma can have focal areas indistinguishable from osteoblastoma. In addition, there is a subset of osteosarcomas, comprising broad interanastomosing trabeculae of bone, that closely mimics and can be misdiagnosed as osteoblastoma. (11) Important histologic features that distinguish it from osteoblastoma include presence of a compact solid proliferation of neoplastic cells in between the bony trabeculae (unlike the single row of osteoblasts seen in osteoblastoma), permeative growth or infiltration beyond the confines of the tumor into adjacent bone or soft tissue, and high mitotic rate. (7)


Although uncommon, osteoblastoma presents with microscopic features that can mimic a variety of other benign as well as malignant entities. Following are important features to be cognizant of: (1) virtually any bone can be affected; (2) it commonly involves the spine, where it has a strong propensity to involve the dorsal vertebral elements as opposed to the body; (3) it can sometimes show locally aggressive growth, which correlates mostly with surgical resectability and possibly with specific histologic features such as prominent epithelioid cell morphology ("aggressive osteoblastoma"); (4) other benign tumors such as osteoid osteoma, aneurysmal bone cyst, giant cell tumor of bone, and sino-orbital osteoma can mimic it histologically; and (5) distinguishing it from osteoblastoma-like osteosarcoma, on the basis of careful evaluation of sometimes subtle cytoarchitectural features, is essential to avoid a misdiagnosis.


(1.) Lucas DR, Unni KK, McLeod RA, O'Connor MI, Sim FH. Osteoblastoma: clinicopathologic study of 306 cases. Hum Pathol. 1994;25(2):117-134.

(2.) McLeod RA, Dahlin DC, Beabout JW. The spectrum of osteoblastoma. AJR Am J Roentgenol. 1976;126(2):321-325.

(3.) Bertoni F, Unni KK, Lucas DR, McLeod RA. Osteoblastoma with cartilaginous matrix: an unusual morphologic presentation in 18 cases. Am J Surg Pathol. 1993;17(1):69-74.

(4.) Mirra JM, Kendrick RA, Kendrick RE. Pseudomalignant osteoblastoma versus arrested osteosarcoma: a case report. Cancer. 1976;37(4):2005-2014.

(5.) Zon Filippi R, Swee RG, Krishnan Unni K. Epithelioid multinodular osteoblastoma: a clinicopathologic analysis of 26 cases. Am J Surg Pathol. 2007;31(8):1265-1268.

(6.) Dorfman HD, Weiss SW. Borderline osteoblastic tumors: problems in the differential diagnosis of aggressive osteoblastoma and low-grade osteosarcoma. Semin Diagn Pathol. 1984;1(3):215-234.

(7.) Della Rocca C, Huvos AG. Osteoblastoma: varied histological presentations with a benign clinical course: an analysis of 55 cases. Am J Surg Pathol. 1996; 20(7):841-850.

(8.) Dahlin DC, Johnson EW Jr. Giant osteoid osteoma. J Bone Joint Surg Am. 1954;36-A(3):559-572.

(9.) Eller R, Sillers M. Common fibro-osseous lesions of the paranasal sinuses. Otolaryngol Clin North Am. 2006;39(3):585-600, x.

(10.) McHugh JB, Mukherji SK, Lucas DR. Sino-orbital osteoma: a clinicopathologic study of 45 surgically treated cases with emphasis on tumors with osteoblastoma-like features. Arch Pathol Lab Med. 2009;133(10):1587 1593.

(11.) Bertoni F, Unni KK, McLeod RA, Dahlin DC. Osteosarcoma resembling osteoblastoma. Cancer. 1985;55(2):416-426.

David R. Lucas, MD

Accepted for publication May 24, 2010.

From the Department of Pathology, University of Michigan, Ann Arbor.

The author has no relevant financial interest in the products or companies described in this article.

Presented at New Frontiers in Pathology: An Update for Practicing Pathologists, University of Michigan, Ann Arbor, October 10, 2009.

Reprints: David R. Lucas, MD, Department of Pathology, University of Michigan, 1500 E Medical Center Dr, Room 2G332, Ann Arbor, MI 48109 (e-mail:
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Author:Lucas, David R.
Publication:Archives of Pathology & Laboratory Medicine
Date:Oct 1, 2010
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