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Osteosarcoma of the mandible- A case report of a rare variantAjay Prakash P1, Shyam Prasad Reddy D2, Madhusudan Rao T3, Jeevan Kumar4

ABSTRACT:

Osteosarcoma (OS), third most common cancer in adolescence,

occurs less frequently than only lymphomas & brain tumours.

Osteosarcoma is a highly malignant bone forming tumor

characterized by frankly to subtly anaplastic stromal cells with

evidence of direct formation of osteoid and/or primitive bone by

these cells. Bone or osteoid formation within tumor is

characteristic of osteosarcoma. OS of the head and neck are

considered by most clinicians to be distinct from OS that arise

in the long bones. OS of the jaws is an exceptionally rare entity

with an incidence of 0.7per million. Jaw osteosarcoma presents

a wide spectrum of clinical and radiological features along with

highly variable histopathology. Small cell OS, a rare histological

subtype, has very infrequently been reported in mandible. In

the present case report, a case of small cell OS in a young male

patient is described along with its clinical, radiological,

histological features, genetic aspects and treatment modalities.

Key words: Osteosarcoma, jaw tumor, malignant bone tumor.

C A S E R E P O R T

doi: 10.5866/4.4.998

1Professor & HOD2&3Senior LecturerDepartment of Oral & Maxillofacial Pathology,Kamineni Institute of Dental Sciences,Sreepuram, Narketpally, Nalgonda Dist. A.P.

4ProfessorDepartment of Oral & Maxillofacial Surgery,Kamineni Institute of Dental Sciences,Sreepuram, Narketpally, Nalgonda Dist. A.P.

Article Info:Received: July 13, 2012;Review Completed: August, 11, 2012;Accepted: September 13, 2012Available Online: January, 2013 (www.nacd.in)© NAD, 2012 - All rights reserved

Email for correspondence:drajayprakash@yahoo.co.in

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INTRODUCTION

Osteosarcoma (OS), most common primary tumor of bone, is a malignant mesenchymal tumorcharacterized frankly to subtly anaplastic stromal cells with evidence of direct formation of osteoid and/orprimitive bone by these cells. Bone or osteoid formation within tumor is characteristic of osteosarcoma. Itaccounts for approximately 20% of sarcomas, 19% of all malignant tumors of bone but only 5% osteosarcomasoccur in jaws. OS of the jaws is an exceptionally rare entity with an incidence of 0.7per million.1-3 Despite itshistopathologic similarities with long bones osteosarcoma, OS of the jaws is biologically different. Jawosteosarcoma presents a wide spectrum of clinical and radiological features along with highly variablehistopathology.

Jaw osteosarcomas usually present in third & fourth decades of life, almost a decade after theirpresentation in long bone tumors. Males are slightly more commonly affected than females. Maxilla & Mandibleare equally involved. Mandibular tumors arise more frequently in posterior body and horizontal ramus,whereas maxillary tumours are discovered more commonly in alveolar ridge, sinus floor, and palate.4

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The most common presenting features areincrease tumour volume, pain, ulceration andneurological disorders. Radiological appearancesmanifest as mixed radiolucent/radiopaque lesion,periodontal ligament widening, radiopaque masseswith moth eaten appearance, codman triangle andsunburst appearance.5 Osteosarcomas arise inseveral clinical settings, including pre-existing boneabnormalities such as Paget’s disease, fibrousdysplasia, giant cell tumor, multipleosteochondroma, bone infarct, chronic osteomyelitis,osteogenesis imperfecta, and with history ofradiation exposure.6

WHO lists several variants that differ inlocation, clinical behaviour and level of cellularatypia. The classical osteosarcoma is the mostfrequent variant which develops in medullary regionof bone & can be subdivided into osteoblastic,chondroblastic and fibroblastic histologic typesdepending upon the type of extracellular matrixproduced by tumor cells. Other histological variantsinclude telangiectatic type, small cell osteosarcoma,giant cell and large cell predominant type etc.6 Herewe describe a case of small cell OS in a young malepatient who is 23yrs old, along with its clinical,radiological, histological features and treatmentmodalities.

Case ReportA 23 year old male patient reported to the

institution with the chief complaint of pain andswelling in the right posterior mandibular region.The swelling was present since two months whichwas slowly grown to the present size, measuringabout 4 x 5 cms in size. Medical, surgical, dental,family and personnel histories were not noteworthy.There were no abnormalities detected on physicalexamination. Extra-oral examination revealed adiffuse, smooth surfaced, hard swelling in themandible, extending anteriorly from the body of themandible to first molar and posteriorly to the angleof the mandible. It was found to be hard, non tenderand firm in consistency on palpation. Intra-orally,the swelling extended from right mandibular secondmolar to the angle of the mandible. Clinicaldifferential diagnosis included ameloblastoma.

The radiographic findings (OPG) showed a largeradiolucency extending from right mandibularsecond molar to the angle of the mandible(figure 1). The inferior border of the mandible wasintact. Incisional biopsy was performed for thehistopathological diagnosis. The slides were stainedwith routine H&E stain. The histopathology showeddense infiltration of soft tissue by small round cellswith scanty cytoplasm that were not arranged inany particular pattern (figure 2, 3). Spindle cells

were also present in few areas (figure 4). Areas oftumor osteoid with bizarre osteocytes were presentvery similar to those seen in conventional OS (figure5). The above histological features in relation to theradiographic findings were suggestive of small cellosteosarcoma. Mandibular resection was performedand there is no evidence of recurrence of the lesion.

DiscussionSmall cell osteosarcoma, a rare histological

subtype of OS, was first described in 1979 by Sim etal as resembling Ewing’s tumor, being made up ofsmall round cells.7 Small cell osteosarcomas havebeen reported from almost every part of the skeleton,including extragnathic craniofacial bones as well asextraskeletal locations.8,9 However small cellosteosarcomas of the jaws are extremely rare withvery few cases published in the literature. The mostcommon clinical presentation of small cellosteosarcoma is pain and swelling with durationsvarying from few days to several months.10

Sometimes patient may also present with numbnessand pathologic fractures.9 In the present case,patient complained of pain and swelling in the rightposterior mandibular region since 2 months.

Radiographically small cell osteosarcomausually shows a poorly demarcated radiolucencywhich may be purely lytic or may be mixed lytic-blastic. Destruction of the cortex with elevation ofthe periosteum - Codman’s triangle - periosteal newbone formation and soft tissue extension has beendescribed. The classic ‘sunburst’ appearance ofosteosarcoma also occurs. In the biopsy, the presenceof calcified matrix in the tumor especially with noosteoid is an important clue to the diagnosis of smallcell osteosarcoma which can otherwise look like anysmall round cell tumor especially Ewing’s sarcoma.9, 10

The histologic picture of small cell osteosarcomaconsists of small round cells arranged in islands orsheets, sometimes separated by septae of densefibrous tissue. In some cases, areas of myxoid tissuemay be present in association with chondroid tissuealong with areas of necrosis. In some cases, the cellsmay be arranged in strands and cords.11 The presentcase showed sheets of round cells with areas of densefibrous tissue. The cells were round to oval in shapewith scanty cytoplasm. Some areas of spindled cellshave also been noted. The nuclei were usually roundor oval showing variability in size. Mitotic figureswere present and varied widely.

Ayala et al have classified the tumor into threehistological types based on cell morphology:12

a. Ewing’s sarcoma - like in which the histologyclosely resembled, Ewing’s sarcoma, with cellsshowing scanty cytoplasm and round nucleiwith fine chromatin and inconspicuous nucleoli;

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b. Lymphoma - like pattern resembling large celllymphoma showing large cells with abundantcytoplasm, round to oval nuclei, finely dispersedchromatin and prominent nucleoli;

c. Spindle cell pattern showed cells with scantycytoplasm and short ovoid or spindle shapednuclei with inconspicuous or no nucleoli.

In tumors with multiple patterns, thepredominant pattern determined the type.According to this classification the present case fitsthe Ewing’s sarcoma like pattern as itpredominantly shows round cells with scantycytoplasm that were not arranged in any particularpattern and few areas of spindle cells. The defininghistologic feature of small cell osteosarcoma is thepresence of osteoid which has been described in eachand every case reported so far. It varies from fine,lace-like deposits around the tumor cells to largerareas or calcified matrix. The present case showedcalcified osteoid in one area, and a smaller area ofuncalcified osteoid with bizarre osteocytes, quitesimilar to that seen in conventional osteosarcoma.

Though the histologic differential diagnosis ofsmall cell osteosarcoma includes several round celltumors, it can be most easily mistaken for eitherEwing’s sarcoma or mesenchymal chondrosarcoma.Ewing’s sarcoma can be considered when the biopsyspecimen does not include any osteoid andmesenchymal chondrosarcoma when there ispresence of cartilage. The cells and nuclei in Ewing’ssarcoma are more uniform than in small cellosteosarcoma. There is no osteoid formation, thoughon occasion, fibrin present between tumor cells maybe mistaken for lacy osteoid. The presence of tumorcartilage may lead one to think of mesenchymalchondrosarcoma. But most of the cases of small cellosteosarcoma show the presence of cartilage alongwith osteoid. Mesenchymal chondrosarcoma doesnot show any osteoid; also, the cartilage formed isusually of low-grade malignancy, whereas high-grade malignant cartilage is seen in small cellosteosarcoma.12

Genetic & Molecular Aspects:Osteosarcoma tumorigenesis has been linked to

alterations in several genes. The first association ofosteosarcoma with an inherited predisposition wasthe observation by Kitchin and Ellsworth thatpatients with bilateral retinoblastoma had anunusually high incidence of osteosarcomasregardless of whether the patient had been treatedwith radiation. They concluded that as patients withbilateral disease had the inherited form ofretinoblastoma that there must be a pleiotropiceffect of the gene for retinoblastoma that resulted

in an increased predisposition for secondaryosteosarcomas. This predisposition was furtherdemonstrated by the observation that osteosarcomatumors from patients with bilateral retinoblastomaunderwent tumor-specific loss of constitutionalheterozygosity (LoH) for the same region ofchromosome 13 that occurred in the retinoblastomatumors. This association was confirmed by theidentification of the retinoblastoma susceptibilitygene (RB1) on human chromosome 13 whichpermitted several groups to demonstrate thatmutations in the RB1 gene occurred in a highpercentage of osteosarcomas.1

The second gene associated with osteosarcomawas the p53 gene. Mutations in the p53 gene werefirst observed in sporadic osteosarcoma. Genes otherthan p53 and RB1 have also been associated withosteosarcoma. High frequencies of allelic loss havebeen detected at 3q and 18q, suggesting that at leasttwo other tumor suppressor genes important inosteosarcoma may exist. HER2/neu (c-erbB-2)overexpression has been observed in approximately40% of cases and has been associated with earlypulmonary metastases and decreased survival.1

Pellin et al. in a study of several round celltumors for the translocation (11:22) (q24:q 12), foundit to be present in Ewing’s sarcomas and PNETs,and absent in other round cell tumors includingsmall cell osteosarcoma.13 A recent study by Lee etal on Fli-1 expression in round cell tumors foundthat it is expressed in Ewing’s sarcoma andlymphoblastic lymphoma and negative inmesenchymal chondrosarcoma and small cellosteosarcoma.14 Further studies are needed in thisarea.

While a review of treatment methods is beyondthe scope of this article, it appears that adjuvantchemotherapy improves the prognosis as comparedto only surgery. Mandibular resection was performedin the present case and there is no evidence ofrecurrence of the lesion. The treatment should bein correlation with the histologic and clinicalbehavior of the lesion. Furthermore, recurrence ofsmall cell osteosarcoma may be long delayed, and along term postoperative follow up is essential to theproper management of these patients.

In summary, osteosarcomas of the jaws havedifferent behavior than those of the long bones. Earlydiagnosis and radical surgery with wide surgicalmargins are the keys to a good outcome. Thediagnosis of this small cell osteosarcoma if notobvious from histology, can be made using adjunctivemolecular genetic techniques. A better prognosis isachieved if diagnosed and treated at an early stage.

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osteosarcoma. J Musculoskel Neuron Interact 2002;2(6):554-560.

2. Baghale K and Motahhary P. Osteosarcoma of the jaws: Aretrospective study. Acta Medica Iranica 2003; 4(2): 113-121.

3. Sorares C.R. et al .Osteosarcoma of mandible initiallyresembling lesion of dental periapex: a case report. RevBras Otorrinolaringol 2005; 71(2)242-245.

4. Balwani SR, Tupaki JV, Barpande SR. Parostealosteosarcoma of the mandible I J Oral Maxillofac Pathol2006; 10(1)10-14.

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6. Devi Charan Shetty, Puneet Ahuja, Aadithya B, RupinderKaur. Histopathological Variants of Jaw Osteosarcoma.International Journal of Pathology; 2009; 7(2): 98-101.

7. Sim et al. Osteosarcoma with small cells simulating Ewing’stumor. J Bone Joint Surg Am, 1979; 61: 207-215.

8. Nora Fe et al. Osteosarcoma of extragnathic craniofacialbones. Mayo Clin Proc, 1983; 58: 268-272.

9. Uma K et al. Small cell osteosarcoma of the mandible: casereport and review of its diagnostic aspects. JOMFP, 2011;15(3): 330-335.

10. Nakajima H, Sim FH, Bond JR, Unni KK. Small cellosteosarcoma of bone. Review of 72 cases. Cancer, 1997;79: 2095-2106.

11. Bertoni et al. The Istituto Rizzoli experience with smallcell osteosarcoma. Cancer, 1989; 64: 2591-2599.

12. Ayyala et al. Small cell osteosarcoma. A clinicopathologicstudy of 27 cases. Cancer, 1989; 64: 2162-2173.

13. Pellin et al. EWS/FLI-1 rearrangement in small round cellsarcomas of b one and soft tissue detected by reversetranscriptase polymerase chain reaction amplification. EurJ Cancer, 1994; 30A: 827-831.

14. Lee AF et al. FLI1distinguishes Ewing’s sarcoma fromsmall cell osteosarcoma and mesenchymal chondrosarcoma.Appl Immunohistochem Mol Morphol, 2011; 19: 233-238.

Figure 1: OPG showing radiolucency extending from rightmandibular second molar to the angle of the mandible, withintact inferior border of the mandible.

Figure 2: H & E stained section showing small round cellsarranged in sheet like pattern (10X).

Figure 3: H & E stained section showing small round cells withscanty cytoplasm (40X).

Figure 4: H & E stained section showing small round cells alongwith few spindle shaped cells dispersed in between (10X).

Figure 5: H & E stained section showing area of osteoid withbizarre osteocytes (10X).