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Contents lists available at ScienceDirect

Journal of Oral and Maxillofacial Surgery,

Medicine, and Pathology
journal homepage: www.elsevier.com/locate/jomsmp

Case report

Giant cell rich osteosarcoma of the jaw—A rare entity and review of
literature
Smitha Sammith Shetty a , Rahul N Dahake b , N Venkadasalapathi b ,
Raghu Radhakrishnan c,∗
a
Department of Oral Pathology, Faculty of Dentistry, Melaka Manipal Medical College, Manipal University, Manipal, 576104, India
b
AOMSI Craniofacial Trauma Fellowship at Hannah Joseph Hospital, Institute of Neurosciences and Trauma, Madurai, 625020, India
c
Department of Oral Pathology, Manipal College of Dental Sciences, Manipal University, Manipal, 576104, India

a r t i c l e i n f o a b s t r a c t

Article history: Giant cell rich osteosarcoma is a rare histological variant of conventional osteosarcoma commonly pre-
Received 22 August 2017 senting in long bones of appendicular skeleton. The occurrence in the mandible is exceptionally rare. Its
Received in revised form radiologic and histologic resemblance to giant cell tumors can pose great diagnostic challenge. We report
22 December 2017
a case of giant cell rich variant of osteosarcoma of the mandible in a 16- year- old male patient.
Accepted 27 December 2017
Available online xxx © 2018 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽

Keywords:
Giant cell rich osteosarcoma
Jaw

1. Introduction
Osteosarcoma (OS) or osteogenic sarcoma, is the most common
primary bone tumor in adolescents and young adults accounting
for nearly 20% of all the sarcomas [1]. In the maxillofacial region,
OS referred to as gnathic osteosarcomas accounts for 4%–6% of
all cases [1]. Giant cell rich osteosarcoma (GCRO) is a rare sub-
type of primary osteogenic sarcoma, which was first reported by
Bathurst et al. in 1986 [2]. GCRO is an undifferentiated sarcoma with
abundant osteoclast- like giant cells and scanty osteoid [2]. Many
of the classical radiographic features of conventional osteosarco-
mas are absent in GCRO and hence its distinction as a subset of
OS and its differentiation from other closely related bone tumors
is of paramount importance [3]. GCRO usually mimics a benign
or malignant osteolytic tumor on the plain radiographs. In addi-
tion, histological differentiation from benign or malignant giant cell
tumors (GCT) is challenging[4], and important due to its aggres-
sively fatal outcome [5]. On review of literature, most of cases of
GCRO has been reported in the extremities [3,6]. To our knowledge
only few cases have been reported in head and neck region which
includes two cases in maxilla [7,8], one case in parotid gland [9] and
two cases in mandible[10,11]. Owing to the different prognosis and
treatment strategies for these tumors, it is important to arrive at
∗ Corresponding author.
E-mail address: raghu.radhakrishnan@gmail.com (R. Radhakrishnan).
the right diagnosis [7]. Here, we report a rare case of giant cell rich
osteosarcoma of the mandible with its characteristic radiological
and histopathological features.
2. Case report
A 16 year old male presented with a complaint of swelling and
pain on the right side of the face with numbness of the lower
lip for duration of two months. On examination, a bony hard
swelling was seen involving entire right side of the face extending
from malar region to lower border of mandible measuring around
7 cms × 6 cms in size (Fig. 1A). Intraoral examination revealed a
well-defined swelling extending beyond the retromolar region
involving the soft tissue covering the anterior ramus of mandible.
Right submandibular lymph nodes were palpable and non-tender.
Orthopantomogram (OPG) showed ill-defined mixed radiolu-
cent radio-opaque lesion extending beyond the tooth 47 (FDI)
into ramus of mandible involving coronoid process and condylar
neck with loss of trabecular pattern (Fig. 1B). CT images revealed
large heterogeneous mixed density lesion involving right half of
mandible with osteoid matrix mineralization with moderately rich
vascularity. Tumor osteoid was seen forming a complex network
radiating from body and angle of mandible, involving whole of
ramus, coronoid process and condylar neck (Fig. 1C). There was
evidence of cortical breach with infiltration of massetric and tem-
poralis muscles. Enlargement of level Ib and IIa lymph nodes on
same side was seen. CT angiography showed rich vascularity from

https://doi.org/10.1016/j.ajoms.2017.12.009
2212-5558/© 2018 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽

Please cite this article in press as: Shetty SS, et al. Giant cell rich osteosarcoma of the jaw—A rare entity and review of literature. J Oral
Maxillofac Surg Med Pathol (2018), https://doi.org/10.1016/j.ajoms.2017.12.009
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Fig. 1. Clinical, radiological and intraoperative findings. (A) Preoperative anterio-posterior and superio-inferior extension of the tumor. (B) OPG showing ill-defined mixed
radiolucent radiopaque lesion extending beyond the tooth 47into ramus of mandible up to condylar neck on right side. (C) Computed tomography image showing a dense
meshwork of dysplastic bone and arterial supply of tumor from external carotid artery. (D) Intraoperative image showing the feeder vessel identified as External Carotid
Artery. (E) Intra operative image showing the surgical excision of tumor (F) Intra operative image showing the reconstruction of mandible.

facial, lingual, ascending pharyngeal, internal maxillary and super-
ficial temporal artery. There was also evidence of engulfment of V3
division of trigeminal nerve. Based on the clinical and radiologi-
cal findings, provisional diagnosis of Telangiectatic Osteosarcoma
(TOS) with lymph node metastasis was considered. The whole body
scans and radiographs were performed which confirmed no sec-
ondary metastasis.
The jaw tumor was approached using Waber Ferguson inci-
sion combined with lower lip split incision. Ligation of external
carotid artery (ECA) was done as the feeders were coming from
ECA branches (Fig. 1D). Access osteotomy was done on right zygo-
matic arch to approach the extension of tumor mass and to get the
safe margins. Then segmental mandibulectomy (Fig. 1E), and recon-
struction was done using stainless steel reconstruction plate with
condyle prosthesis (Fig. 1F). The possibility of secondary metastasis
was ruled out and hence the patient was treated with surgery alone
by complete resection of the tumor. No chemotherapy or radio-
therapy was given. Post –surgery the patient pursued good clinical
course with no recurrence and was disease free. The patient’s last
follow up visit after 11 months post-surgery showed no recurrence
(Fig. 3).
Histopathological examination of the excised specimen showed
pleomorphic tumor arranged in fascicular pattern as well as in
sheets. The tumor cells were highly pleomorphic with some of
them ovoid to round or spindle shaped. Numerous osteoclast
like giant cells containing large pleomorphic nuclei with irregu-
lar nuclear membrane and few showing prominent nucleoli were
present (Fig. 2A, B). The tumor cells had vesicular nuclei and numer-
ous mitotic figures were seen (Fig. 2C). Areas of lace like osteoid
deposits around the tumor cells and bone destruction was evident
(Fig. 2D). Blood filled cystic spaces or vascular spaces were lacking
hence the provisional diagnosis of Telangiectatic osteosarcoma was
ruled out and definite diagnosis of giant cell rich osteosarcoma was
arrived.
3. Discussion
Osteosarcoma is a malignancy of the mesenchymal cells that
have the ability to produce osteoid or immature bone [12]. It usu-
ally arises in the medullary cavity of the metaphysis of a growing
long tubular bone and is rare in jaws [11]. GCRO is a rare histo-
logic variant of conventional osteosarcoma [7]. Bathurst used the
term “osteoclast-rich osteosarcoma” to denote “an undifferentiated
sarcoma with scanty or no tumor osteoid, in which the sarcoma
cells are more or less swamped by osteoclasts producing a striking
resemblance to a tumor osteoid, leads to its easy confusion with
giant cell tumor during biopsy interpretation [5].
Although the number of craniofacial osteosarcomas is very low,
the prevalence of jaw osteosarcoma is in fact 10 times greater
than that of osteosarcoma in the total body skeleton, considering

Please cite this article in press as: Shetty SS, et al. Giant cell rich osteosarcoma of the jaw—A rare entity and review of literature. J Oral
Maxillofac Surg Med Pathol (2018), https://doi.org/10.1016/j.ajoms.2017.12.009
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Fig. 2. Representative histological sections stained with Haematoxylin-Eosin stain. (A) Osteoclast-like giant cells, admixed with pleomorphic stromal tumor cells (x400). (B)
Numerous multinucleated giant cells admixed with stromal cells (x100). (C) Pleomorphic cells with hyperchromatic nucleus, and prominent nucleoli with mitotic figures
(x100). (D) Areas of bone destruction and osteoid formation (x400).

Fig. 3. Follow up clinical (A, B), intraoral (C) and radiological (D) images revealing no evidence of recurrence after 11 months post-surgery.

that jaws represent only 0.86% of total body volume [13]. GCRO elderly individuals with female predilection. Mandible being more
in long bones are seen to present in younger patients with mean frequently involved than the maxilla, with posterior body, hori-
age of 26yrs, with male predilection [4]. Review of literature on zontal ramus and the ascending ramus being the most commonly
GCRO in the head and neck region (Table 1) shows its occurrence in affected sites [14]. The average duration of symptoms before it is

Please cite this article in press as: Shetty SS, et al. Giant cell rich osteosarcoma of the jaw—A rare entity and review of literature. J Oral
Maxillofac Surg Med Pathol (2018), https://doi.org/10.1016/j.ajoms.2017.12.009
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diagnosed is reported to be 3–4 months [15]. Swelling, pain and

with Recurrence after three

years, metastasis after 3 yr.

No recurrence on 1 month
No recurrence during 1 yr.
general discomfort are the unusual nonspecific clinical findings

45 months of follow up
[15]. Osteosarcoma may arise de novo or several epidemiological

No recurrence on 11
months of follow up
Died after 6 months
risk factors have been related to the development of OS, including

No data available
history of ionizing radiation exposure, fibrous dysplasia, retinoblas-
toma or history of trauma [13]. In our case of GCRO, the patient was

of follow up
follow up
8 months
Outcome

a 16yr old boy with involvement of right mandible with no history

of any risk factors previously.
The radiological features of GCRO are different from the con-
ventional osteosarcomas. They mimic benign or malignant giant

Segmental Maxillectomy
cell tumors, [6] and usually present as osteolytic lesion both in
Total maxillectomy and

head and neck region (Table 1) and in long bones [4]. In our case,
mandibulectomy,
Surgical excision,
radiotherapy and

radiotherapy and

Surgical excision,
radiotherapy and
OPG revealed an ill-defined mixed radiolucent radiopaque lesion.

mandibulectomy
chemotherapy

chemotherapy

chemotherapy
Also 3D CT scan revealed an large tumor mass with tumor osteoid
radiotherapy
Segmental

Segmental
Treatment

forming a complex network radiating from body, angle of mandible

Round, ovoid, spindle pleomorphic tumor cells CT showed large heterogeneous mixed density
right parotid gland region, no involvement of
destruction of nasal septum, anterior wall of
and involving whole of ramus and condylar neck and also the
feeder vessel was seen depicting a highly vascular bone tumor and
hence provisional diagnosis of Telangiectatic osteosarcoma (TOS)
was given.

PET/CT revealed large soft tissue mass in the

tissue mass occupying the whole of maxilla,

lesion involving right half of mandible with

CT revealed maxillary bone expansion and

Histopathologically, the diagnosis of GCRO is challenging due to

CT showed an expansile, hyperdense soft

its close resemblance to benign or malignant giant cell tumors [6].

GCRO is an undifferentiated sarcoma with scanty osteoid formation
and numerous osteoclast-like giant cells dominating the picture,
osteoid matrix mineralization
maxilla and floor of the orbit.

which produces a striking resemblance to giant cell tumor; how-

destruction of cortical bone

ever the presence of osteoid formation by the tumor cells gives a

clue for diagnosis [7]. About 13–25% of cases of osteosarcoma, are
Radiological findings

accompanied by few osteoclast-like giant cells which are often seen

Osteolytic lesion

in haemorrhagic and perivascular areas [16], but the histology of

Lytic lesion

GCRO presents with large number of osteoclast-like giant cells sim-

mandible

ilar to giant cell tumors [4]. Previously reported cases of GCRO in

head and neck region also show these characteristic histopatho-
logical features. (Table 1), but one of the case was misdiagnosed
Numerous giant cells, areas of lace like osteoid

previously as malignancy in giant cell tumor probably due to sparse

Pleomorphic tumor cells in fascicular pattern.

cells, dyshesive epithelioid malignant cells

osteoid formation which was missed out [10].

Numerous clusters of osteoclast-like giant
Sheets of plump spindle cells, with atypia,

sarcoma cells swamped by osteoclast-like

numerous multinucleated osteoclasts like

and numerous osteoclast like giant cells

Our case presented with highly pleomorphic tumor cells with

Atypical mononuclear cells, numerous

numerous osteoclast like giant cells and scanty areas osteoid

giant cells, and osteoid formation

deposits. Hence the final diagnosis of GCRO was considered. The

with areas of osteoid formation
giant cells and scanty osteoid

provisional diagnosis of Telangiectatcic osteosarcoma (TOS) was

Histopathological features

osteoclasts like-giant cells

ruled out based on the diagnostic criteria given by Matsuno T

et al.,[17] that suggests, histologically the tumor should consist of
single or multiple ‘cystic’ cavities with blood or necrotic tumor and
anaplastic-appearing cells should be seen in the periphery of cyst
like zones, with areas of lace like osteoid formation [18].
formation

To conclude, the GCRO is a very rare subtype of osteosarco-

mas showing striking histologic and radiologic similarity to giant
Reported cases of Giant cell rich osteosarcoma in head and neck region.

cell tumors. Inclusion of GCRO in the differential diagnosis of any

osteolytic lesion of the jaw is mandatory. In view of excessive
sternum and first thoracic

(Metastasis to both lungs)

Mandible (metastasis to

vascularity associated with the osteolytic lesion of the jaw, and

particularly when associated in a younger individual, telengiectatic
osteosarcoma (TOS) needs to be ruled out. While CT imaging offered
Parotid gland

valuable leads in suggesting the diagnosis of vascular lesions,

absence of vascular spaces, very typical of TOS was evidently miss-
Mandible

Mandible
vertebra)

Maxilla

Maxilla

ing on histopathological observation, thus ruling out TOS. The role

Site

of imaging techniques complemented by histopathology aided in

the early diagnosis, prompt surgical intervention and improved
prognosis.
62yrs/M

64yrs/M

16yrs/M
Age/Sex

28yrs/F

67yrs/F

56yrs/F

References
Verma RK et al. [7]

[1] Kalburge JV, Sahuji SK, Kalburge V, Kini Y. Osteosarcoma of mandible. J Clin
Sun LM et al. [10]

Hirose K et al. [8]

Fu HH et al. [11]

Diagn Res 2012;6(9):1597–9.

[2] Bathurst N, Sanerkin N, Watt L. Osteoclast-rich osteosarcoma. Br J Radiol
Huang EC [9]

Present case

1986;59:667–73.
[3] Chow LTC. Giant cell rich osteosarcoma revisited-diagnostic criteria and
Author
Table 1

histopathologic patterns, Ki67, CDK4, and MDM2 expression, changes in

response to bisphosphonate and denosumab treatment. Virchows Arch
2016;468:741–55.

Please cite this article in press as: Shetty SS, et al. Giant cell rich osteosarcoma of the jaw—A rare entity and review of literature. J Oral
Maxillofac Surg Med Pathol (2018), https://doi.org/10.1016/j.ajoms.2017.12.009
G Model
JOMSMP-707; No. of Pages 5 ARTICLE IN PRESS
S.S. Shetty et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2018) xxx–xxx
[4] Wang CS, Yin QH, Liao JS, Lou JH, Ding XY, Zhu YB. Giant cell-rich
osteosarcoma in long bones: clinical, radiological and pathological features.
Radiol Med 2013;118:1324–34.
[5] Chow LTC. Fibular giant cell-rich osteosarcoma virtually indistinguishable
radiographically and histopathologically from giant cell tumor-analysis of
subtle differentiating features. APMIS 2015;123:530–9.
[6] Hong SJ, Kim KA, Yong HS, Choi JW, Suh Il S, Lee JH, et al. Giant cell-rich
osteosarcoma of bone. Eur J Radiol Extra 2005;53:87–90.
[7] Verma RK, Gupta G, Bal A, Yadav J. Primary giant cell rich osteosarcoma of
maxilla: an unusual case report. J Maxillofac Oral Surg 2011;10(2):159–62.
[8] Hirose K, Okura M, Sato S, Murakami S, Ikeda JI, Noda Y, et al. Gnathic
giant-cell-rich conventional osteosarcoma with MDM2 and CDK4 gene
amplification. Histopathology 2017;70:1171–9.
[9] Huang EC, Ghazikhanian V, Qian X. Giant cell-rich osteosarcoma of the parotid
gland: an exceptionally rare entity at an unusual site. Diagn Cytopathol
2016;44(12):1107–11.
[10] Sun LM, Zhang QF, Tang N, Mi XY, Qiu XS. Giant cell rich osteosarcoma of the
mandible with abundant spindle cells and osteoclast-like giant cells
mimicking malignancy in giant cell tumor. Int J Clin Exp Pathol
2015;8(8):9718–22.
Please cite this article in press as: Shetty SS, et al. Giant cell rich osteosarcoma of the jaw—A rare entity and review of literature. J Oral
Maxillofac Surg Med Pathol (2018), https://doi.org/10.1016/j.ajoms.2017.12.009
5
[11] Fu HH, Zhuang QW, He J, Wang LZ, He Y. Giant cell-rich osteosarcoma or giant
cell reparative granuloma of the mandible? J Craniofac Surg
2011;22(3):1136–9.
[12] Arora P, Rehman F, Girish KL, Kalra M. Osteosarcoma of mandible: detailed
radiographic assessment of a case. Contemp Clin Dent 2013;4(3):382–5.
[13] Bhojan A, Christy W, Chanmougananda S, Ashokan K. Osteosarcoma of
mandible: a case report and review of literature. J Clin Diagn Res
2012;6(4):753–7.
[14] Chaudhary M, Chaudhary SD. Osteosarcoma of jaws. J Oral Maxillofac Pathol
2012;16(2):233–8.
[15] van den Berg H, Schreuder WH, de Lange J. Osteosarcoma: a comparison of
jaw versus nonjaw localizations and review of the literature. Sarcoma
2013;2013:316123.
[16] Troup JB, Dahlin DC, Coventry MB. The significance of giant cells in osteogenic
sarcoma. Do they indicate a relationship between osteogenic sarcoma and
giant cell tumor of bone? Proc Staff Meet Mayo Clin 1960;35:179–86.
[17] Tomar D, Dhillon M, Thayath MN, Zaidi I, Singh S. Central telangiectatic
osteosarcoma of the mandible in a paediatric patient: a rarity. J Clin
Diagnostic Res 2016;10(12):10–2.
[18] Matsuno T, Unni krishanan K, Mecleod RA, Dahlin DC. Telangiectatic
osteogenic sarcoma. Cancer 1976;38:2538–47.