Osteoblastoma of the mandible: a case report with immunohistochemical evaluation

doi:10.4236/ojst.2011.14032

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Open Journal of Stomatology, 2011, 1, 207-211

doi:10.4236/ojst.2011.14032 Published Online December 2011 (http://www.SciRP.org/journal/ojst/ OJST

Published Online December 2011 in SciRes. http://www.scirp.org/journal/OJST

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.

Email: [email protected]

Received 19 September 2011; revised 23 October 2011; accepted 5 November 2011.

ABSTRACT

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-

mors

1. INTRODUCTION

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.

2. CASE REPORT

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

208

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).

DISCUSSION

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-

blastoma.

(a)

(b)

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

E. Chrysomali et al. / Open Journal of Stomatology 1 (2011) 207-211

209

Figure 2. (a) Trabeculae rimmed by polygonal cells resembling osteoblasts; few sparse

multinucleated

osteoclast-like giant

cells (arrows) are noted (HXE, original magnification ×120); (b)

Irregularly

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

cells

for bcl-2 immunostaining; (d) Weak positivity of stromal cells (marked with asterisks)

for

Ki67 immunostaining.

Figure 3. Orthopantomogram of the patient after micro-plate

remova l.

Figure 4. CT scan of the patient 2 years

postoperatively.

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-

OJST

E. Chrysomali et al. / Open Journal of Stomatology 1 (2011) 207-211

210

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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