pathology

Osteosarcoma of the maxilla and the maxillary sinus:A case reportChristian Frei, Dr med der tVMichael M, Bornstein, Dr med dentVEdcuard Stauffer, Dr medVTateyuki lizuka, Prof Dr med, Dr med dent"/ Daniei Buser, Prof Dr med

Osteosarcoma of the jawbones is a rare malignant mesenchyrral neoplasm witti the tendency for newbone being directly tormed by the tumor oeiis. Clinicafiy, the tumor may be central or peripheral—per ¡osteal—and histologicaliy can be divided into three subtypes: osteoblastic, fibroblastic, and chondro-biastic. This report presents a case cl a central osteoblastic osteosarcoma of the ieft maxillary tuberosityand maxiiiary sinus. Problems related tc definitive diagnosis and therapy are described and discussed.(Quintessence Int 2004:35:228-233)

Key words: diagnosis, histologie criteria, interdisciplinary treatment, maxilla, osteosarcoma

The term osteosarcoma defines a malignant mes-encbymal neoplasm with the tendency for bone

formation.' Osteosarcomas of the jawbones are rareand account for 5% to 6% of ali osteosarcomas. Theestimated incidence is approximately 0.07 cases per100,000 per year,2'

Clinically, the tumor may be central or perlpberal-periosteal-and bistologicaiiy can be divided into tbreesubtypes: osteoblastic, fibrobiastic, and cbondroblastic.There seems to be a difference in the clinical behaviorof osteosarcomas of the jawbones (OS]) and osteosar-comas of tbe long bones (particuiariy distai femoraimetbapbysis, proximai tibia, and bumerai methaph-

' Post gradua te Student, Departmenl of Oral Surgery and Stomatology,School of Dental Medicine, Uniuersity ot Berne, Berne, Switzerland.

^Senior Lecturer, Department of Oral Surgery and Slomatology, School ofDental Medicine, Unfversily of Berne, Beme, Switzerland.

^Assistant Professor, Institute ot Pathology, University ot Berne, Berne,Switzerland.

"Associate Protessor, Department of Craniomaxillofacial Suigery,University Hospital ot Berne, Berne, Switzerland.

^Professor and Ctiairman, Department of Oral Surgery and Stomatology,School of Dental fuledicine, University of Berne, Berne, Switzerland.

Reprint requests: Dr Michael ful. Bornstein, Department of Oral Surgeryand Stomalology, School ot Dental Medicine, Freiburgstrasse 7, CH-3010Berne, Switzerland. E-mail' micbaet.Dornstein@zmk.unibe.ch

ysis). OSJ are diagnosed 10 years iaier, usualiy in thethird and fourth decade, show a minor tendency formetastasis, and generally have a better prognosis thanosteosarcomas of the long bones. Their frequency isslightly higber in males, and tbey are more often lo-cated ¡n the mandible.''' Typical dinical signs for OS]are the following: intra- and/or extraorai sweiiing,loosening and change in position of teeth, proptosis,neurologic deficits, and limitation of mouth opening.Radioiogicaiiy, a widened periodontai ligament ¡n peri-apicai radiographs of teeth located in the area of themahgnoma often is seen. In many cases, these signsare present without pain; therefore, patients often seekmedical care in a more advanced stage of the disease.

The current therapy of choice is total surgical re-moval of the lesion with safe margins. Radio- andchemotherapy seem to be less effective. '

The following case report demonstrates and discussesthe problems ¡n establishing the final diagnosis and thesubsequent interdisciplinary tberapy of an osteoblasticosteosarcoma of the maxilla and the maxillary sinus

CASE REPORT

A 50-year-old man was referred to the Department ofOral Surgery and Stomatology, University of Berne,

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• Frei e l al

Rg 1 Clinical aspect (occlusal view) at the firsi consuttatim: Asweffing of ihe ten maxiilaiy tubenosity and ttie fibiin-covered ex-traction socket of the maxilla/y left iMsdotn tooth are visible.

Rg 2 C l in ; ; = ; L ^ - ' c.:cal view) at the firsl consultation; Notethe séquestre &: :•;= ...--ijcn of the buccaf gingiva and the alveo-lar mucosa in lhe region of ate thiid molar.

for evaluation and further treatment. The referringdentist had obser\'ed a hard and painless swelling inthe region of the carious ma\illar\' left third molar ap-proximately 6 months prior. The tooth was asstuned tobe the reason for the swelling and was extracted.Subsequently, the lesion did not disappear but in-creased in size. The patient denied any significantmedical history, had no knowTi drug allergies, was nottaking any medicine, and was not consuming alcoholor tobacco-

Extraoral examination revealed no swelling of theleft side of the face. On palpation, there was a hardand painless induration belott' the left zygomatic bone.Mouth opening was not limited, wth a distance be-tween the incisors of more than 40 mm. The cervicaland submandibular lymph nodes showed no patho-logic findings.

Intraoially. there was a hard and painless swellingto the buccal and palatal aspect in the region of themaxillary lefl molars and maxillary tuberosity. The ex-traction socket of the maxillary third molar was stillnot healed and showed fibrin covering (Fig 1). At thejunction of the buccal gingiva and the alveolar mucosain the region of the left third molar, there was a mobilebony sequestra visible, measuring approximately3 x 3 mm (Fig 2). The second premolar and secondmolar, supporting a fixed partial denture, showed in-creased mobifi^ and probing depths up to 10 tnm. Thesecond premolar reacted positively to cold pulp tesdng-Hje second molar had a previous root canal treatment.

The panoramic radiograph showed inhomogeneousradiopacity in the region of the maxillary left molarsand maxillary tuberosiW- The floor of the left maxillarySintis was not cieariy visible (Fig 3). The bony seques-tra in the region of the maxiilari' left molar was re-moved without local anesthesia and sent for histologie

Rg 3 The preoperative panoramic radiograoh shows ihe opacityv/rfli uncieai [»rders in ttie region oi ¡he left maxillary pjberosiiyand sinus-

examination (first biopsy). TTie clinical and radiologiefindings indicated a malignant lesion: therefore, the pa-tient was referred to the Department of Craniomaxillo-facial Surgery. University Hospital of Berne, on thesame day-

The histologie analysis of the hony sequestra (firstbiopsi') sbowed immature bone with necrosis, moder-ate cellular atypia. and signs of infiammation {Fig 4).These findings were consistent with an infected se-questra but gave no definitive conclusion about the di-agnosis of the lesion.

Further radiographie imaging, including computedtomography scan (CT) and magnefic resonance imag-ing (MRI). was performed, and the MRI showed alar^e expansile lesion of the left maxilla involving themaxillary' sinus without signs of infiltrafion or destruc-tion of the surrounding fissues. In the CT scan, signs ofcalcification were evident in the susceptible lesion (Figs5 and 6). Because tbe clinical, radiologie, and pathohis-tologic findings were not conclusive, a large bony

Quintessence Internatkxial

Fig 4 The histoiogic view of the bony se-questra (lirsl biopsy) shows immature bonewith necrosis, moderate cellular alypia, andpurulent inflammation (hematOKylin-eosinslain; original magnification x2Q)

Fig 5 The preoperative axiai CT scanshows the bony mass in the region of theieft maxiiiary tuberosity.

Fig 6 The preoperative coronal CT scanshows the bony mass m the region of ttieleft maxiliary tuberosity and the swollen mu-cosa of the maxiiiary sinus.

Fig 7 The histoiogic view ot the secondbiopsy shows hyperceliuiar lumgr compo-nents with immature bone, o = osteoid: ac= atypical oelis {hematoxyiin-eosin stain;originai magnjficaticn x20).

Fig 8 (right) The preoperatívü three-phaseskeietai sointigraphy shows no metastasis inany other region of the body. The highiy in-creased metaboiism of the tumor tissue isshown by the biack spol in the ieft maxilla.

Fig 9 The tumor specimen after surgicaibiock resection from an occiusai view.

biopsy of the left maxilla and the maxillary sinus (sec-ond biopsy) was performed under general anesthesia.

The histoiogic analysis of this second biopsy showedhyperceliuiar tumor components with immature bone(osteoid), atypical cells, atypical mitotic figures, littlechondroid differentiation, and infiltration of adjacentsoft tissue (Fig 7), The histomorphologic criteria wereconsistent with those of an osteoblastic osteosarcoma.

To exclude eventual distant metastasis, a three-phase skeletal scintigraphy (Fig 8) and a thoracal CTscan were performed. In both the scintigraphy and CTscan, no signs of metastasis could be found. As defini-tive treatment, radical surgical excision of the primarytumor with subsequent chemotherapy was performed.

En bloc removal of the lesion was performed by apartial maxillectomy under general anesthesia (Fig 9),Intraorally, a sublabial incision was made and the mu-cosa overlying the left lateral wall of the maxilla was

elevated. The dissection of the soft tissue was ex-tended posteriorly to the pterygoid plates. The initialosteotomy was made using a sagittal saw vertically atthe left alveolar ridge between the canine and the firstpremolar. The vertical extent of the osteotomy wastaken directly inferior to the infraorbital foramen pre-serving the nerve. The vertical osteotomy was ex-tended posteriorly along the anterior and lateral wallsof the maxillary sinus in a horizontal fashion to in-clude the medial and lateral pterygoid plates. A cuff ofthe pteiygoid muscles was taken with the specimen. Amedian sagittal osteotomy was also performed throughthe hard palate to connect to the lateral osteotomysite. A portion of the soft palate was resected to in-clude a L5-cm margin around the tumor.

The primary reconstruction of the defect was per-formed using a pedicied temporalis muscle flap andfree calvarium bone grafts with expectation of dental

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Bg 10 The harvesleo iree calvarium bone grafts. Fig 11 " r -:: z-n z ; e», DÎ :h6 luf^iji" specimen shows a hy-percellular mslignant lumor witti immature bone, osteoid (o).wfiich is produced by atypical ceils (ac) (bematQ)!yiir>eosin slain;originai magnification xáo).

implants in the future. Harv'esting the flap and bonegrafts was done through a hemicoronal incision. Theincision was extended to the preauricuiar crease toexpose the zygomatic arch. The size of the bony defect«as carefully measured, and appropriate split calvarialbone grafts were barvested from the parietal skull.Four pieces of split caivarium measuring approxi-mately 1.5 X 3.0 cm were harvested (Fig 10). The har-vested split calvarium was used to reconstruct thealveolar ridge and fixed to the remaining wali of themaxillary sinus using a titanium plating system(Modus System, Medartis). Dissection of a temporalismuscle flap was performed in the deep layer of the su-perficial fascia. Anterior and posterior zygomatic os-teotomies were done to allow for rotation of the flap.Tlie mtiscle flap was rotated into the site of the bonydefect through the site of the zygomatic osteotomies.Pedicled buccal fat was also mobilized into the defectto provide soft tissue coverage of the inner side of thebone graft. After release and rotation of the flap, thezi-gomatic osteotomies were fixed into position usinga titanium miniplate (Modus System, Medartis).Finally, the entire defect including the bone graft wascovered by the temporalis muscie flap. The flap wassecured to the border of tbe oral mucosa with ab-sortable sutures.

After excision, the tumor specimen was analyzedhistologie ally, and the definitive diagnosis by thepathologist was a predominantly osteoblastic high-grade osteosarcoma «ith focally chondroid differentia-tion. The histologie presentation was a hj'percellularmalignant timior with immature bone (osteoid), pro-duced hy atypical cells, atypical mitotic figures, fewfocal chondroid differentiation, and infiltration of ad-jacent soft tissue (Fig 11). Excision borders were freeof tumor. All around the block resection, a minimaldistance of 5 mm was seen from the tumor to the exci-sion horders. The specimen also showed an intact ep-itheiium of the ma:dllary sinus.

The postoperative course was uneventful. Followingsurgery, the patient undenvent an adjuvant chemo-therapy consisting of eight cycles of adriblastin andifosphamid/platinol agents. The patient also receivedconcurrent assistance with neupogen (recombinant G-CSF) treatment.

In the first year after surger\'. the patient was seenon a monthly basis according to the cancer protocol ofthe Department of Craniomaxillofacial Surgery,University' Hospital of Berne.

DISCUSSION

Predisposing factors for OSJ discussed in the literatureare Paget's disease," trauma to bone, prewous radia-tion therapy, existing bone pathology (for example, fi-brous dysplasia). and/or genetic predisposition.^^*-"In the present case, none of the predisposing factorsmentioned above could be confirmed with the avail-able anamnestic. clinical, or radiologie data. Traumato tbe bone tbrough the extraction of the carious max-

' left third molar can almost be excluded with cer-because the swelling in tbe left maxilla was al-

ready present before the exuaction. The progression ofthe osteosarcoma could have been accelerated by theextraction oí the maxillary third molar.'- Althoughciinicai and radiographie signs indicated malignancy, 'it was first after an open biopsy of the left maxilla andthe maxillary sinus (second hiopsy) that diagnosiscould be established.

In the same osteosarcoma, different bistologic as-pects such as osteoblastic. chondroblastic. fibroblastic,and teleangiectatic areas can be seen. Typical histo-logie criteria for diagnosis of a bigh-grade osteosar-eoma are the following: bypercellular malignanttumor, immature bone formation (osteoid) producedby atypical tumor celis without osteohlasts, atypicalmitotic figures, infiltration of adjacent soft tissue, and

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in tbis case, few focal cbondroid differentiation.Almost decisive for tbe definitive diagnosis is tbe find-ing of tumor osteoid, wbicb atypical mesencbymalcells bave produced," Tbe diagnosis of osteosarcomahas severe and invasive tberapeutic consequences fortbe patient, and tberefore, it is very important to con-firm such a diagnosis by a reference institute. In tbepresent case, tbe bistologic specimens were presentedto and discussed witb Prof Dr med G, Jundt, DÖSAKreference registry. Institute of Patbology, UniversityHospital of Basel, Basel, Switzerland,

To successfully treat osteosarcomas witb pre-dictable long-term results, radical resection bas beenproven to be tbe most important factor,'''-'^ In OSJ,metastasis in regional lymph nodes is rare, A neck dis-section in combination with tbe surgical excision oftbe primary lesion is only necessary if regional lymphnodes bave been tested positively,"

Adjuvant chemotherapy in the treatment of os-teosarcomas of the long bones bas a beneficial effecton the 5-year survival rate,'"-'' For surgery alone, tbe 5-year survival rate was around lS /o; for surgery in com-bination witb cbemotberapy it was 60% to 80%, InOSJ, significant improvement of tbe survival rate withthe help of chemotherapy bas been questioned,^''^^"Additionally, it was sbown tbat adjuvant radlotberapybas no positive effect on tbe survival rate.-'

Tbe general practitioner bas an important role intbe detection of premalignant and malignant lesions.Malignancies are rare and in tbeir initial stages oftenwitbout symptoms, Tbe so-called "patient delay"-tbetime from patient awareness of the lesion to tbe firstconsultation of a doctor-cannot be influenced bymedical personnel,^' In tbe present case, the "patientdelay" seems not to have been very long because tbepatient went to his practitioner immediately afternoticing the swelling in the left maxilla. The "doctor/professional de!ay"-the time from the first scheduledvisit to the finding of the definitive diagnosis and sub-sequent treatment-can ciearly be reduced with im-proved educafion of medical and dental professionals.In tbe present case, the "professional delay" was quitelong-approximately 6 months, Furtbermore, the heal-ing disturbance of the extraction socket was not con-sidered as a warning sign. Only after further progres-sion of the swelling in the left tnaxilla did thepractitioner refer the patient to the Department ofOra) Surgery and Stomatology for further diagnosisand treatment. With the delayed finding of the defini-tive diagnosis, the surgical resection was aggressiveand reconstrucfion more difficult than it would havebeen in an earher stage of tbe disease. The aim ofmedical and dental practitioners is to recognize poten-tial malignant processes as soon as possible and torefer tbem for diagnosis and treatment at a medicai

center offering an interdisciplinary tberapeutic ap-proach between general practitioners, oral and max-illofacial surgeons, patbologists, radiologists, and on-cologists. Only witb tbis procedure can malignanciesbe diagnosed and treated in tbeir eariy stages withpredictable long-term success.

ACKNOWLEDGMENTS

The authors gratefully acknowledge the assistance in the final prepa-ration of Ihe paper by Prof Dr E, Hjürtmg-Hansen, Denmark, andalso would like to express their gralitude to Prol" Di G, Jundl,Switzerland, for his expertise in bone pathology and tonfirraation ofthe definitive diagnosis. The authors also thank Dr Karl Dula,Swiizeriand. for his radiologie advice.

REFERENCES

Mittermayer C, Oralpathologie, Erkrankungcti der Mund-region, Lehrbuch für Zahnmedizin, Mund- und Kieferheil-liunde, 3. env, Auflage, Stuttgart: Schattauer, 1993:255-256.Mardinger O, Givol N, Talmi YP, Taicher S. Osteosarcomaof the jaw. The Chaim Sheba Medical Cetiter experiertce.Oral Surg Oral Med Oral Pathol Ural Radiol Ertdod2001;91:445-451,

Clark IL, Unni KK, Dahlin DC, Devine KD, Osteosarcotnaof the jaw. Cancer 1983;51:2311-2316,Van Es RJJ, Kcus RB, Van der Waal 1, Koole R, Vemiey A.Osteosarcoma of tbe jaw bones: Long-term follow up of 4Scases, Int J Oral Masillofac Surg 1997;26.191-197,August M, Magennis P, Dewitt D, Osteogenetic sarcoma ofthe jaws: Factors influencing prognosis. Int J OralMaxillofac Surg 1997;26:198-204.Gardner DG, Mills DM. The widened periodontal ligamentof osteosarcgma of the jaws. Oral Surg Oral Med OralPathol 1975;41:652-636,Smeele LE, Kostense PJ, Van der Waal I, Snow GB, Effectof chemotherapy on survival of craniofacial osteosarcoma:A systemic review of 20t patients, J Clin Oncol 1997;15:363-367,

Dahlin DC, Covetitry MB, Osteogenic sarcoma, A study ofsix hundred cases. J Bone joint Surg Am 1967;49:101-110,Chindia ML, Osteosarcoma of the jaw bones. Oral Oncoi-ogv2001;37;545-547,Bennett JH, Thomas G, Evans AW, Speigbf PM. Osteosar-coma of the jaws: A 30-year retrospective review. Oral SurgOral Med Oral Pathol Oral Radiol Endod 2000;90:323-333.Mock D, Rosen IB, Osteosarcotna in irradiated fihrous dys-plasia, J Orai Pathül 1986;15:l-4,

Daffner RH, Fox KR, Galey KR. Fibrohlastic osteosarcomaof the mandible. Skeletal Radiol 2002;31:107-lll,Bianchi SD, Boccardi A. Radiological aspects of osteosar-coma of the jaws, Dento maxillofac Radiol 1999;28:42-47.Jundt G, Prein J. Bone tumors and tumor-like lesions in thejaw. Findings of the Basel DÖSAK reference registry, MundIOefer Gesichts Chir 2000;4(suppl l);196-207.

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Frei et al

15. Snede LE, \ ^ der V/aat JE, Dies« PJ. Van der Wüal 1, SnowGB- Radical suigtcal treatment in craniofacial osteosarcoma^pes e.xcellent suivii-al; A retrospective cohort snidj' of H pa-ñoits. Ora] Oncol EUT J Cancer 1994^50 B 274-276.

16. Russ JE. Jesse RH. Management of osteosarcoma of themasilla and mandible. Am J Surg 1980:140:572-576.

Dl De^do R. Maafe £. Alfeiran A. et aL Osteosarcoma of thejaw. Head Neck 1994:16:246-252.

18, ftan CB. Champion ¡E. Fleming ID. et al. Adjuvant chemo-therapy for osteosarcoma of the extremity': Long term re-sults of iwo consecutive prospective protocol studies.Cancer 1990:65 43 &-445.

19- Ëuher FB. Rosen G. Adjuvant chemotherapy of osteosar-coma. Semin Oncol 1989:16:312-322,

20. Mark RJ. Sercarz JA. Tran L. Dodd LG. Selch M, CalcaterraTC- Osieogenic sarcoma of the head and neck. The UCLAexperience. -i\rch Otolan-ngot Head Neck Surg 1991;1I7:761-766.

21. Arndt V. Stunner T. Steigmaier C, Ziegler H. Dhom G.Biermer H- Patient delay and stage of diagnosis amongbreast cancer patients in Germany—A population hasedsmdr. Br J Cancer 2002:86:1034-1040-

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