Braz J Oral Sci. October/December 2002 - Vol. 1 - Number 3
Head and neck osteosarcomas –
A review of the literature
Ademar Takahama Junior 1a
Fábio de Abreu Alves 1b
Clóvis Antonio Lopes Pinto 2
André Lopes Carvalho 3
Luiz Paulo Kowalski 3
Márcio Ajudarte Lopes 1b
D.D.S., M.Sc., Department of Oral Diagnosis,
Piracicaba Dental School, University of
Campinas, Brazil.
1b
D.D.S., Ph.D., Department of Oral Diagnosis,
Piracicaba Dental School, University of
Campinas, Brazil.
2
M.D., Ph.D., Department of Pathology, A.C.
Camargo Cancer Hospital, São Paulo, Brazil.
3
M.D., Ph.D., Head and Neck Surgery and
Otorhinolaryngology Department, A.C.
Camargo Cancer Hospital, São Paulo, Brazil.
1a
Recebimento: 16/10/02
Aceite: 17/10/02
Abstract
Osteosarcoma (OS) is a rare and aggressive malignant bone tumor,
which occurs more frequently in long bones of young people. About
10% of the cases affect the head and neck region presenting peculiar
features. The main sites of this tumor in head and neck are the mandible followed by the maxilla, and it seems to have a similar distribution between the genders. The most common clinical feature is the
local swelling. Pain and paresthesia may be present in some cases. The
early signs of this tumor in the jaw bones can be a dental mobility or
widening of the periodontal ligament space. The diagnosis of OS is
established with histological examination, which shows malignant mesenchymal cells producing osteoid or bone. The main modality treatment for head and neck OS is surgical resection with wide margins. The
benefits of adjuvant therapies like chemotherapy and radiotherapy are
still not clear. The major complication is local recurrence, with metastasis occurring as a solitary or a late stage event.
Key Words:
Osteosarcoma, head and neck.
Correspondence to:
Márcio Ajudarte Lopes, DDS, PhD.
Department of Oral Diagnosis
Piracicaba Dental School, UNICAMP.
Av. Limeira, 901- Areião - Piracicaba/SP CEP: 13.414.900 - Brazil.
Phone: +55-19-3412-5319
Fax: +55-193412-5218
e-mail: [email protected]
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Braz J Oral Sci. 1(3):112-115
Introduction
Sarcomas are malignant tumors originating from
mesenchymal cells. They are very rare mainly in head and
neck and most of them involve soft tissues. Osteosarcoma
(OS) is an aggressive malignant bone tumor, which has the
ability of produce bone tissue1. This tumor is extremely
rare in head and neck and few studies about it have been
reported in the English-language literature. The purpose of
this article is to show some information about this tumor in
a review of the literature.
Epidemiology
Osteosarcoma is the most common malignant primary bone
tumor and affects more commonly long bones of children
and young adults, corresponding to the third most common
malignancy in adolescents 2. In the United States of America
its incidence is about one case in 100,000 people per year.
Any bone of the skeleton can be affected1.
About 10% of all cases occur in head and neck region3,4,
affecting older people if compared to the long bone tumors,
between the third or fourth decade of life with a similar
gender distribution5. The main sites of the OS in head and
neck are the mandible followed by the maxilla4.
Etiology
The exact etiology of OS is still unknown, however some
predisposing factors have been associated with the
development of this tumor. Ionizing radiation used in cancer
therapy may induce development of OS 6. Dickens et al.7
(1990) reported that 4 patients in 1,000 who received
radiation therapy for the treatment of nasopharingeal
carcinoma developed OS in head and neck region. Mark et
al. 5 (1994) studying 37 cases of post-radiation sarcomas
found 4 cases of OS. The latent period between the
radiotherapy and the development of the secondary tumor
is approximately 13-years and the neoplasm is almost
always high-grade tumor with a poor prognosis8.
Another condition related with OS is the Paget´s disease,
which affects old patients. However, the incidence of OS
arising in Paget´s disease is probably less than 1% 8. In
these cases, the OS is also highly malignant, and the
prognosis is worse than of conventional osteosarcomas.
Some studies have also reported OS arising from fibrous
dysplasia, but in the majority of these cases the patients
had been treated with radiotherapy.
Molecular biology studies have reported alterations in
specifics genes in patients with OS. Among these genes
we can bring out the P53, Rb (retinoblastoma) and genes
localized in the region q13-15 of chromosome 12 like the
MDM2 (murine double minute 2), CDK4 (cyclin dependent
kinase) and SAS (sarcoma amplified sequence) 9.
Clinical Features
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Head and neck osteosarcomas – A review of the literature
Clinically the main sign of head and neck OS is the local
swelling (Figs. 1 and 2). Other features like pain, paresthesia
and ulceration can also be found10. Mardinger et al.11 (2001)
studying 14 cases of head and neck OS found that in all
cases there were local swelling and in all the cases with the
involvement of the mandibular body there were also
paresthesia. Tazawa et al.12 (1991) observed that pain was
present in 4% of the cases.
The average interval from onset of sign and symptoms to
the diagnosis is 5 months 10. However, in some cases we
can find history of years of evolution, suggesting slow
growing 12.
Figure 1. Clinical aspect of a mandibular osteosarcoma showing
local swelling.
Figure 2. Intra-oral view of the same case presenting an ulcerated
tumor.
Radiographic Features
The radiographic appearance of head and neck OS can have
three patterns: sclerotic, osteolytic (Fig. 3) and mixed. In
some cases OS may destroy cortical bone, cause widening
of periodontal ligament space and may result in a spiculated
pattern of new bone formation called by some author as
“sun-burst” aspect13. Lindquist et al.14 (1986) reported that
Braz J Oral Sci. 1(3):112-115
the “sun-burst” aspect and the widening of periodontal
ligament space are almost patognomonic of OS of the
jaws.
Radiographic widening of the mandibular canal or the
periodontal ligament space are characteristics that can
be found as the first sign of the OS in the jaw bones 10.
Petrikowski et al.13 (1995) reported that is very difficult to
differentiate radiographically OS from others bone lesions
like fibrous dysplasia and osteomyelitis.
The computed tomography and the nuclear magnetic
resonance are exams that can be performed to observe
the intra and extramedular involvement, calcifications and
invasion of the adjacent tissues 15 .
Histological Features
The diagnosis of OS is performed with the histological
features. Microscopically malignant mesenchymal cells
producing osteoid or bone tissue characterize the OS.
These cells are usually spindle shaped, but they may be
small, epithelioid or multinucleated and almost always
show marked atypia8.
According to the histologic differentiation, OS can be
classified in osteoblastic, chondroblastic or fibroblastic
(Figs. 4 and 5). The osteoblastic type represents 50% of
all osteosarcomas and is characterized by malignant cells
that produce large amounts of osteoid. Rarely the matrix
is mature and trabecular. The chondroblastic
osteosarcoma has a predominant chondroid differentiation
and the cartilage cells have pronounced atypia and are
arranged in lobules. The osteoid or bone production can
be seen in the periphery of these lobules. The fibroblastic
type is the less common and It is characterized by
predominance of spindle-cell proliferation similar to that
seen in fibrosarcomas. The osteoid production is
minimal and focal 8.
In long bones the osteoblastic type is predominant. On
the other hand, chondroblastic osteosarcoma has been
reported as the most common in the head and neck 3,4,16.
According to the grade of malignancy, OS can be
classified in high-grade, intermediate-grade or low-grade
tumor (Fig. 6). Clark et al. 16 (1983) reported that the
majority of the head and neck OS were high grade. Other
authors also found a predominance of high-grade OS in
head and neck 11,15,17 . Low-grade intraosseous OS is rare,
and they are often inappropriately diagnosed as a benign
tumor like fibrous dysplasia and osteoblastoma 10.
There are few methods that can be used for the diagnosis
of OS. The osteocalcin, a bone specific protein may be
useful to distinguish osteosarcoma from malignant
fibrous histiocytoma. Collagen type 1 and osteonectin
have been recognized in osteoid tumor, but these
proteins are not specific to malignant tissue 18.
Head and neck osteosarcomas – A review of the literature
Fig. 3. Panoramic radiographic appearance displaying pathological
fracture of the right mandibular body.
Fig. 4. Histologic aspect of a chondroblastic-type osteosarcoma showing areas of
malignant chondroid differentiation and areas of bone formation (H&E-200x).
Fig. 5. Osteoblastic-type osteosarcoma showing predominance of
bone formation (H&E-100x).
Fig. 6. Pleomorphic malignant cells in a high-grade osteosarcoma
(H&E-400x).
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Braz J Oral Sci. 1(3):112-115
Head and neck osteosarcomas – A review of the literature
Treatment
Effective treatment of head and neck OS requires cooperation
among members of a multidisciplinary team including head
and neck surgeon, oncologist, pathologist, radiation
oncologist, neurosurgeon, dentist, nurse, nutricionist,
phonoaudiologist, physiotherapist and others.
The main treatment modality for head and neck
osteosarcomas is an adequate surgical resection with wide
margins5,15. However, due to the anatomic characteristics of
the head and neck region the surgical resection may be
difficult19.
Owing to the high incidence of metastasis in long bones OS,
the chemotherapy was introduced. Nowadays with the
multidrug therapy and high-dose treatment, the
chemotherapy has improved the prognosis in patients with
long bones OS and the main drugs used are metrotrexate,
doxorrubicin, cisplatin and ifosfamide2. The chemotherapy
can also be administrated before the surgery, as neo-adjuvant
treatment, which role is to reduce the tumor promoting
necrosis and to test the sensibility of the tumor to the drugs.
However, the efficacy of the chemotherapy in head and neck
OS is not clear. Smeele et al.20 (1997) reported survival
improvement in patients with adjuvant chemotherapy.
However, the majority of the studies does not show any
change in survival15,19.
The radiation therapy can also be used in the treatment of
head and neck OS, but is necessary more than 6,000 cGy to
have some effect1. The efficacy of the radiotherapy improving
the prognosis is still unknown because it has been used
only in cases of advanced tumors, local recurrences and
metastasis 7.
tumors that affect the jaw bones. According to Clark et al.16
(1983) the chondroblastic-type tumor has a better prognosis
when comparing to the osteoblastic type. In patients with
history of radiotherapy or Paget´s disease, OS has also a
poor prognosis 8.
In head and neck the prognosis is better in young patients
treated with radical surgical ressection3,4,17,20. Patients treated
with radical surgery with free margins have a 5-year overall
survival of about 80% and the most important factor for
survival in patients with head and neck OS is adequacy of
primary operation6.
Local Recurrence and Metastasis
The main complication of the head and neck OS is the local
spread and recurrence 10. Head and neck OS has a high
tendency for local recurrence 19. About 33% of the cases
developed local recurrence15. Local recurrence is extremely
difficult to be managed and has a negative impact on quality
of life3.
The distant metastasis are uncommon in head and neck OS
comparing to the cases affecting the long bones, and occurs
as a late stage event10. About 18% of the head and neck OS
present metastasis and the main sites are the lungs, other
bones and the liver11. The involvement of the regional lymph
nodes is not common3.
12.
Prognosis
Head and neck OS is known to present a better prognosis
compared to the long bones OS16. However, new studies
have reported that a long-term survival is lower than 35%,
mainly due to the local relapse. The 5-year overall survival is
about 50% in the majority of the studies5,6.
Skull lesions have the worst prognosis comparing to
115
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