Osteoblastoma is an uncommon primary neoplasm of the bone. It has clinical and histological manifestations similar to those of osteoid osteoma; therefore, some consider the two tumors to be variants of the same disease, with osteoblastoma representing a giant osteoid osteoma. However, an aggressive type of osteoblastoma has been recognized, making the relationship less clear.

There is continuing debate in the literature regarding recurrent aggressive osteoblastic lesions with epithelioid osteoblasts, as to whether these represent benign, locally aggressive lesions [1] or osteosarcomas. [2]

Aggressive osteoblastoma has unpredictable clinical course. A case of aggressive osteoblastoma is presented which had three recurrences along with implantation of tumor at surgical site and pulmonary metastasis over a period of 3 years and 4 months.

A 23-year-old male, presented with mild pain at the dorsum of hand around wrist joint. Thereafter gradually increasing 2x2 cm, hard, non mobile and non tender swelling appeared around the same region over a period of 2 months. On X-ray osteolytic lesion of hemate bone was detected. Excisional biopsy was performed and it was diagnosed as osteoblastoma on histopathology. After 11 months 2x3 cm, hard, fixed non tender tumor recurred for which patient was reoperated and rods were implanted along with bony chips taken from right iliac bone. Unfortunately, 2x3 cm hard fixed non-tender tumor again recurred after a year for which patient was reoperated and rods were implanted along with bony chips which were now taken from left iliac bone. Lesion was diagnosed as osteoblastoma with active osteoblastic activity on histopathological investigation.

Third recurrence of tumor (4x4 cm) occurred after five months and level of alkaline phosphatase was raised (343 IU/L). Below left elbow joint amputation was performed. Patient was lost in the follow up. After 1 year 2 months, patient again reported in the outpatient department with 6x5 cm swelling in right iliac region which had developed over a period of three months. Retrospective history suggested asymptomatic period of 11 months followed by development of a small swelling in right iliac region (Figures 1 and 2). Level of alkaline phosphatase had increased further (840 IU/L) during 1 year. The digital pulmonary skiagram showed multiple round radiopaque shadows in the upper lobes of both the lungs suggestive of metastasis. Fine needle aspiration cytology (FNAC) was done from right iliac swelling.

On FNAC highly cellular smears consisting of oval osteoblastic cells with eccentric nuclei and dense eosinophilic cytoplasm were obtained. Some of these cells had characteristics 'hof'–a feature of activated osteoblasts. Multinucleated giant cells were abundant in the smears with occasional mitotic figures (Figure 3). Atypical mitosis and nuclear pleomorphism was evident. Cytomorphologic features, size more than 4 cm and frequent recurrence of previous lesions favored the diagnosis of aggressive osteoblastoma, which was later confirmed by histopathological examination.

Osteoblastoma is a benign lesion, which is differentiated from osteoid osteoma by the large size of the nidus (> 1.5 cm), the absence of surrounding reactive new bone formation and lack of intense pain. [3] Microscopically, osteoblastoma is well demarcated from the surrounding bone and is composed of haphazardly deposited trabeculae of woven bone rimmed by osteoblasts and scattered osteoclasts within richly vascular stroma. Cytomorphologically, the osteoblasts in conventional tumors are ovoid or round with eccentric nuclei and moderate amount of eosinophilic cytoplasm. Mitoses are uncommon and necrosis is usally absent. [4] Aggressive osteoblastoma is very rare tumor that is considered as borderline between benign osteoblastomas and osteosarcomas. [5] They have a higher growth potential than conventional osteoblastomas and are typically more than 4 cm in size with high risk of recurrence. [5] They are distinguished microscopically from the ordinary osteoblasts because of the presence of wider or more irregular trabecula, which is bordered by epithelioid appearing osteoblasts, by the focal lack of a trabecular pattern of the osteoid proliferation. [1] Aspirates from aggressive osteoblastoma are highly cellular and the osteoblasts are two to three times larger than the conventional osteoblasts and have abundant eosinophilic cytoplasm with vesicular nuclei and prominent nuclei (epithelioid osteoblasts). [4] The presence of epithelioid osteoblasts is the main differentiating point between conventional osteoblastoma and aggressive osteoblastoma (Table 1).[5]

The complex presentation of this case presented two diagnostic dilemmas. One was whether to consider this tumor as aggressive osteoblastoma or as low grade/well differentiated osteosarcoma. Morphologic features, involvement of short and flat bones, long duration of illness and diagnosis of osteoblastoma in hemate bone were in favor of diagnosis of aggressive osteoblastoma. Aggressive osteoblastoma is differentiated from conventional osteosarcoma due to low mitotic rate and the absence of the following features: lace-like osteoid, permeation of surrounding intertrabecular spaces and atypical mitoses. [6] Aspirates from osteosarcoma are highly cellular. Osteosarcoma cells are spindled, oval, rounded, or pleomorphic, and show high degree of cellular atypia. Intracellular and/or extracellular osteiod may be present (Table 2). [5]

Second problem was to establish whether the tumor developed de novo, or was it a metastasis of osteoblastoma, or weather it developed due to implantation during surgery. The implantation theory was given weightage due to the development of tumor in the iliac bone following sampling for bone chips.

The histopathological study of biopsy from right iliac region showed abundant osteoid with numerous empty as well as nucleated osteocytic lacunae separated by lacy osteoid matrix. The osteoid had numerous blotchy areas of calcification and a few entrapped dysplastic osteoblastic as well as spindle shaped cells (Figure 4). A small island of proliferating osteoblasts, showing well defined darkly stained nucleus and abundant deeply eosinophilic cytoplasm was seen at the periphery. Another small area showed proliferating spindle shaped fibroblastic type cells with aggressive appearing nuclei. Occasional multinucleated osteoclastic giant cells as well as a few small bi and tri nucleated giant cells were also appreciated. These findings favored the diagnosis of aggressive osteoblastoma.

Mark et al. [7] have reported two cases of aggressive osteoblastoma exhibiting diverse biological behavior. One was in iliac bone of 15 years old male patient. The patient died despite curettage, extensive chemotherapy, and radiotherapy. On autopsy distant metastases were detected. The other case was in femur of 12 years old female patient. Amputation was recommended following recurrence, but the patient declined and radiation therapy was given. Patient survived up to next 14 years on radiotherapy. [7] Two unusual cases have been reported in maxillary bone. Both the cases were initially diagnosed as osteoblastoma, but later it was suggested as a malignant transformation of osteoblastoma into osteosarcoma. [8] One case has been reported in calcaneum of a 29-year-old female, which was initially diagnosed as benign osteoblastoma but after recurrence, revised diagnosis of aggressive osteoblastoma was established on histology. [9] Osteoblastoma with conversion to osteosarcoma should be considered as a separate tumor entity distinguished from genuine osteosarcoma. [10] However, it is very difficult to differentiate between aggressive osteoblastoma and low grade/well differentiated osteosarcoma [11] both radiologically and histologically. The presence of epithelioid osteoblasts, trabecular osteoid, prominent osteoclastic activity, absence of cartilage, well demarcated woven bone-host bone interface and low mitotic activity are some of the histological criteria to differentiate it from osteosarcoma.

These cases highlight the biological diversity of osteoblastoma like lesions and illustrate the difficulties which may be encountered in attempting to differentiate between benign and malignant forms of osteoblastoma and between aggressive osteoblastoma and osteosarcoma.

1. Dorfman HD, Weiss SW. Borderline osteoblastic tumors: problems in the differential diagnosis of aggressive osteoblastoma and low grade osteosarcoma. Semin Diagn Pathol 1984;1:215–34.   [Pubmed]    
2. Bertoni F, Unni KK, McLeod RA, Dahlin DC. Osteosarcoma resembling osteoblastoma. Cancer 1985;11:416–26.   [CrossRef]   [Pubmed]    
3. Dahlin DC, Johnson EW. Giant osteoid osteoma. J Bone Joint Surg 1954 Jun;36-A(3):559–72.   [Pubmed]    
4. Nielsen GP, Layfield LJ, Rosenberg AE. Noeplastic and tumor like lesions of bone. In: Silverberg SG DeLellis RA, Frable W J LiVolsi VA, Wick MR, Ed. Silverberg's principles and practices of surgical pathology and cytopathology. 4th ed. China: Churchill Livingstone, Elsevier 2006:725.    
5. Koss Leopold G. Koss' Diagnostic cytology & its histopathologic bases. 5th ed. Philadelphia: Lippincott Williams & Wilkins 2006:1343–48.    
6. Schajowicz F, Lemos C. Malignant osteoblastoma. J Bone Joint Surg Br 1976;58;202–11.   [Pubmed]    
7. Mark L Mitchell, Lauren V Ackerman. Metastatic and pseudomalignant osteoblastoma: a report of two unusual cases. Skeletal Radiology 1986 March;15(3):213–8.   [CrossRef]   [Pubmed]    
8. Hiroshi Ueno, Ei-ichiro Ariji, Takemasa Tanaka, et al. Imaging features of maxillary osteoblastoma and its malignant transformation. Skeletal Radiol 1994 Oct;23(7):509-12.   [CrossRef]   [Pubmed]    
9. Miyayama H, Sakamoto K, Ide M, et al. Aggressive osteoblastoma of the calcaneus. Cancer 1993;71:346–53.   [CrossRef]   [Pubmed]    
10. Kunze E, Enderle A, Radig K, Schneider-Stock R. Aggressive osteoblastoma with focal malignant transformation and development of pulmonary metastases. A case report with a review of literature. Gen Diagn Pathol 1996 May;141(5-6):377–92.   [Pubmed]    
11. Mirra JM. Bone In: "Surgical Pathology" Ed. WF Coulson JB. Philadelphia: Lippincott Co 1988:1356–471.