Open Journal of Stomatology, 2011, 1, 207-211
doi:10.4236/ojst.2011.14032 Published Online December 2011 ( OJST
Published Online December 2011 in SciRes.
Osteoblastoma of the mandible: a case report with
immunohistochemical evaluation
Evanthia Chrysomali1, Ourania Schoinohoriti2, Nadia Theologie-Lygidakis2,
Lambros Goutzanis2, Ioannis Iatrou2
1Department of Oral Pathology and Medicine, School of Dentistry, University of Athens, Athens, Greece;
2Department of Oral and Maxillofacial Surgery, Children’s Hospital “P. and A. Kyriakou”, School of Dentistry, University of Athens,
Athens, Greece.
Received 19 September 2011; revised 23 October 2011; accepted 5 November 2011.
Background: Osteoblastoma, a rare osteoblastic tumor,
constitutes approximately 1% of all primary bo ne tu-
mors. Aim: The purpose of this report is to present
an osteoblastoma of the mandible, with particular
emphasis on the differential diagnosis of this rare tu-
mor. Methods-Results: the lesion showed osteoblast-
like cells, stromal cells, osteoclast-like cells and inter-
lacing trabeculae of osteoid. Because of the high cel-
lularity of the tumor, immunohistochemical analysis
was performed using the cell proliferation marker
Ki-67, the p53 and the anti-apoptotic protein Bcl-2.
The lesion demonstrated low to moderate prolifera-
tive activity and no immunoreactivity was detected
for p53. An interesting finding was the Bcl-2 expres-
sion by the multinucleated osteoclast-like giant cells,
in contrast to the lack of Bcl-2 expression from osteo-
blast-like and stromal tumor cells. Conclusions: To our
knowledge the Bcl-2 expression has not yet been in-
vestigated in benign or malignant osteoblastic tumors.
This finding may be related to the molecular mecha-
nisms regulating the apoptosis of osteoclast-like tu-
mor cells or their function.
Keywords: Osteoblastoma; Mandible; Reconstruction;
Immunohistochemistry; Ki-67; Bcl-2; p53; Bone Tu-
Osteoblastoma represents about 1% of all primary bone
tumors. Approximately 11% of the bone osteoblastomas
are localized to the skull and nearly half of these cases
involve the mandilble [1,2]. Osteoblastoma usually ap-
pears in the second decade of life as a painful expans ion
of the bone cortex with non specific radiographic appea-
rance. Histologically, it is characterized by osteoblast-
like cells proliferation forming trabeculae of osteoid and
immature bone in a highly vascularized stroma [2-6].
These cells are usually uniform in the benign or “classi-
cal” osteoblastoma, but they may exhibit nuclear hyper-
chromatism or/and pleomorphism with features of epi-
thelioid appearance in the “atypical type” of osteoblas-
toma [5,7].
The most important diagnostic consideration is to dif-
ferentiate osteoblastoma from osteoblastic osteosarcoma,
especially in case of a borderline osteoblastic lesion in-
termediate osteoblastoma and osteosarcoma [2,4,5,7]. In
the maxillofacial region the diagnosis of osteoblastoma
is often difficult and careful clinicopathological correla-
tion may be needed, since many jaw lesions may present
similar overlapping demographic, clinical, radiographic
and histopat hological features [3 ,4] .
The purpose of this article is to present a case of os-
teoblastoma involving the anterior mandible with parti-
cular emphasis on the differential diagnosis and the im-
munohistochemical features of this rare tumor using the
cell proliferation marker Ki67, the p53 and the anti-
apoptotic protein Bcl-2.
A 14-year-old female with free medical history was re-
ferred to our clinic because of a 6-month history of pro-
gressive painful discomfort located to the anterior man-
dible. Oral examination showed a minimal expansion of
the labial cortex at the anterior parasymphysal area of
the mandible related to the incisors, canines and right
first premolar. Motility of the adjacent teeth was noted,
but the teeth were vital. There was no paraesthesia, the
overlying mucosa was intact and no regional lymph
nodes were palpable. Orthopantomogram revealed an
irregularly-shaped radiolucency without sclerotic bor-
ders, in the anterior mandible extending from the right
first premolar to the left canine and from the alveolar
E. Chrysomali et al. / Open Journal of Stomatology 1 (2011) 207-211
crest to the body of the mandible producing root dis-
placement, but not resorption (Figure 1(a)). Computed
tomography scan (Figure 1(b)) showed a radiodense le-
sion with a peripheral rim of calcification perforating
both labial and lingual cortices centrally and expanding
the labial cortex peripherally.
The histopathological examination, after an incisional
biopsy, showed benign osteoblastic tumor consistent
with osteoblastoma. An en bloc resection of the tumor
was decided under general anaesthesia. The gross biopsy
specimen consisted of a relatively compact mass of red-
dish to brown friable tumor tissue with irregular surface,
resected with a macroscopically healthy block of mandi-
bular bone, measuring 4 × 2 × 2.5 cm. After lavish irri-
gation the osseous defect was reconstructed with a bone
graft (a block of cortical bone measuring 2 × 2.5 × 0.5
cm along with chips of cancellous bone) harvested from
the anterior iliac crest at the same surgical time.
Histologically, the lesion showed relatively high cellu-
larity consisting of osteoblast-like cells, stromal cells, os-
teoclast-like cells, immature bone and osteoid deposition.
The interlacing, irregularly-shaped bone trabeculae show-
ed variable thickness and maturation and rimmed by a
line of osteoblast-like polygonal cells with abundant eo-
sinophilic cytoplasm and round to oval nuclei (Figure
2(a)). Multinucleated osteoclast-like giant cells were
Figure 1. (a) Preoperative orthopantomogram (a) and (b) pre-
operative CT scan.
dispersed through the tumor among spindle shaped stro-
mal cells (Figure 2(b)). Numerous large dilated capil-
laries, as well as focal hemorrhage were seen in the in-
ter-trabecular stroma of loose fibrovascular tissue. Epi-
thelioid osteoblasts, cytologic atypia, or pleomorphism
were not observed. There was no evidence of infiltrated
residual bone suggestive of permeative growth pattern.
The final diagnosis was osteoblastoma excised upon
healthy margins. Because of the highly cellular histopa-
thologic appearance and the occasional, but not abnor-
mal, mitotic activity, immunohistochemical analysis was
performed using a strepta-avidin-biotin system and mo-
noclonal antibodies to Ki-67 antigen (clone MIB-1, Da-
ko), p53 protein (clone DO7, Dako) and Bcl-2 protein
(clone 124, Dako, Glostrup, Denmark). A strong Bcl-2
protein immunoreactivity was detected in the cytoplasm
of multinucleated osteoclast-lik e cells but limited, if any,
reactivity in the stromal and osteoblast-like cells (Figure
2(c)). A weak expression for Ki-67 was detectable in the
nuclei of osteoblast-like and stromal cells, in a percent-
age ranging from 10 % to 25% of the tumor cells (Figure
2(d)), while no immunoreact ivity was detected for p53.
The patient recovered well; she was asymptomatic
without any signs of recurrence on follow-up evaluation
after one year. After the micro-plate was removed, an
orthopantomogram revealed the excellent osseous inte-
gration of the graft (Figure 3). A CT scan of the patient
2 years postoperatively documented the lack of recur-
rence at the operative site (Figure 4).
The differential diagnosis of osteoblastoma includes many
jawbone lesions. This case was differentiated from os-
teoid osteoma due to the lack of the characteristic central
bone nidus, which is a feature seen in osteoid osteoma
[3,4,8]. The clinical findings, such as the large tumor size
(over 2 cm) and the symptoms (pain, local tenderness/
discomfort) are features usually associated with osteo-
blastoma [2-4]. Because of the histopathological similar-
ity of osteoblastoma with cementoblastoma, the distinc-
tion between them is difficult, but the unique character-
istic feature of the latter is its fusion to the root of the ad-
jacent tooth [4]. The tumor was closely related to the
adjacent teeth displacing the roots in our case, but it was
not fused to them excluding the diagnosis of cemento-
The term “aggressive osteoblastoma” has been consi-
dered appropriate for a subset of lesions which display
locally aggressive growth pattern and have atypical
histopathological features [5,7]. Aggressive or atypical
osteoblastoma is distinguished from classical osteoblas-
toma due to the presence of large epithelioid, bizarre
looking osteoblasts, more osteoclast-like giant cells and
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Figure 2. (a) Trabeculae rimmed by polygonal cells resembling osteoblasts; few sparse
osteoclast-like giant
cells (arrows) are noted (HXE, original magnification ×120); (b)
shaped and variably thick bone trabeculae and
osteoid deposition (HXE, original magnification
×25); (
c) Positivity of the multinucleated osteoclast-like giant cells and
negativity of the osteoblast-like
for bcl-2 immunostaining; (d) Weak positivity of stromal cells (marked with asterisks)
Ki67 immunostaining.
Figure 3. Orthopantomogram of the patient after micro-plate
remova l.
Figure 4. CT scan of the patient 2 years
more abundant atypical osteoid. Because of the variable
histological appearance of osteoblastoma, differentiation from osteosarcoma may occasionally be challenging, but
the presence of dysplastic features, fine compacted lace-
E. Chrysomali et al. / Open Journal of Stomatology 1 (2011) 207-211
like osteoid strands, invasion into host bone, high rate of
mitotic activity or atypical mitoses aid in the diagnosis
of osteosarcoma [1,2,4,5].
Despite the high cellularity in th e case presented here,
there was no evidence of epithelioid or dysplastic fea-
tures, or growth pattern suggestive of malignancy. The
Ki-67 immunostaining disclosed a relatively low to mo-
derate cell proliferation index and th e tumor cells did not
show any immunoreactivity fo r the p53 protein. Oliveira
et al. investigated the cell proliferation marker PCNA, as
well as the p53 immunohistochemical expression and
p53 gene mutations in classical, atypical osteoblastomas
in comparison to osteosarcomas [7]. Atypical osteoblas-
tomas, osteosarcomas and tumor recurrence were statis-
tically correlated with a high PCNA labelling index and
p53 immunoexpression [7].
The histopathological and immunohistochemical find-
ings in our case were indicative for the classical osteo-
blastoma. A long follow-up period may be needed to draw
firm conclusions concerning the benign or potential ag-
gressive clinical course of this lesion. Aggressive beha-
vior may be within the biologic spectrum of osteoblas-
tomas; the histopathology may not appear to be a reli-
able predictor of aggressiveness [1]. The predictive val-
ue of cell proliferation or other molecular markers in the
biologic behavior of osteoblastoma variants remains to
be completely determined.
The Bcl-2 gene and its protein product promote cellu-
lar survival; therefore correlation of the Bcl-2 expression
with clinical outcome has been examined in many types
of tumors. Recently the Bcl-2 protein expression has
been correlated—along with other biomarkers—with the
progression and prognosis of osteosarcoma [9]; however
its expression has not yet, to our knowledge, been in-
vestigated in benign osteoblastic tumors. An interesting
finding in the present case was the immunohistochemi-
cal detection of the Bcl-2 protein in the multinucleated
osteoclast-like giant cells, in contrast to the lack of ex-
pression of this protein in the osteoblast-like and stro mal
tumor cells. This finding may be related to the molecular
mechanisms regulating the apoptosis of osteoclast-like
tumor cells or their function. Anti-apoptotic Bcl-2 family
members such as Bcl-2 and Bcl-xL seem to play a sig-
nificant role, not only in the apoptosis of osteoclasts, but
also in the bone resorbing function of these cells [10].
The treatment options of osteoblastoma include con-
servative surgical excision, excision with vigorous cu-
rettage followed by bur ablation of the margins and co-
pious irritation or en block resection [4]. Local recur-
rence related to inadequately removed tumors have been
reported in a rate of 14% [11]. Lesions treated with en
bloc resection or resection yielding tumor-free margins
exhibit minimal likelihood of recurrence; we believe that
such radical procedures are fully justified in pediatric
patients suffering from potentially aggressive lesions
like osteoblastomas. Despite the propensity of recurren-
ce, primary reconstruction seems to be worthwhile, and
should be taken into account when mandibular integrity
can be preserved. Long-term follow-up is recommended,
of at least 2 years, not only to minimize the risk of un-
diagnosed recurrence, but also to guarantee the grafts’
survival and integ ration.
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