Osteogenic sarcoma of the maxilla and mandible

Osteogenic sarcoma of the maxilla and mandible G. Forteza, M.D., * B. Colmenero, Madrid, Spain CIUDAD

SANITARIA

M.D., D.D.Sc., * and F. Lbpez-Barea,

“LA PAZ” DE LA SEGURIDAD

SOCIAL,

HOSPITAL

M.D., **

GENERAL

Osteogenic sarcoma of the maxilla and mandible is a peculiar entity within the context of the malignant bone tumors of other sites. In our series of nine cases the mean age at appearance 44.5%

of the tumors affected the maxilla, and 55.5%

was 34.1 years;

affected the mandible. Most of the tumors were

principally rapidly growing and painless or minimally painful masses. Histopathologically. the fibroblastic type was the most frequent, with prevalence of Broders’ Grades Ill and IV. Radical surgery was the only therapeutic procedure in 87.5% of the series, producing a survival of 85%. Overall survival for all the therapeutic categories was 75%, with a mean disease-free

interval of 8 years. In the remaining cases,

local recurrence and intracranial invasion were the main causes of death. (ORAL SURC. ORAL MED. ORAL PATHOL.62:179-184,

1986)

0

steogenic sarcoma is the most common primary bone tumor (17% to 2 1%) in persons under the age of 40 years’, 2 and affects the maxilla and mandible in about 6.5% of cases.3 According to some,*13 its frequency is 0.07 to 0.4/ 100,000 persons. The tumor occurs most often in the long bones, with a predilection for the distal femoral metaphysis, proximal tibia, and humeral metaphysis. The mortality associated with tumors in these locations is high, with 5-year survival approximating 20K4 In the maxilla and mandible, the presentation of the tumor at a later age (around the fourth decade) and its higher survival rate help to differentiate it from osteogenic sarcomas in other locations. MATERIALS

AND METHODS

A review was done on eighty-one cases of osteosarcoma in patients who were at “La Paz” Hospital between 1967 and 1985. Of these eighty-one cases, eleven tumors were in the maxilla and mandible. Nine were selected from the eleven for review because they were the only ones with sufficient clinical, radiologic, and histopathologic data for inclusion and analysis. The pathologic study was This study was supported by Caja de Ahorros y Monte de Piedad of Madrid. *Maxillofacial Surgery Service. **Department of Pathology.

based on tissue from surgical specimens from the following: two partial resections, nine radical resections, and four recurrences from a single patient. The material was fixed in 10% formaldehyde, embedded in paraffin, and stained with hematoxylin and eosin, and in some cases with Masson’s trichrome stain. RESULTS

Of the nine patients included in this study, four were males (44.5%) and five were females (55.5%). The mean age of these patients when the tumor was initially seen was 34.1 years. The ages were distributed mainly between the second, third, and fourth decades. The upper and lower limits of the range were 65 and 13 years, respectively. No significant relation was found between the age at initial appearance and tumor location or between sex and the age at initial appearance of the tumor. Four tumors affected the maxilla, and five affected the mandible. The maxillary tumors were predominant in female patients (4: l), with the mandibular lesions occurring only in the male patients. Three of the maxillary sarcomas were in the antrum and alveolar ridge (in most cases it was impossible to differentiate these origins); one tumor was in the incisor area. Two cases originated in the body of the mandible, one was in the ascending ramus, and two were in the parasymphyseal region. None of the cases had antecedents of Paget’s 179

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Fig. 1. Panoramic radiograph of 13-year-old boy showing lytic and sclerotic lesion corresponding osteogenic sarcoma of right ascending ramus of the mandible. Table

I. Symptoms present at first consultation Symptom

No. of cases

Tumor Pain Mucosal ulceration Infraorbital paresthesia Tooth mobility

9 4 3 2 2

Table II.

Broders’ index classification Grade

No. of cases

I II III IV Unclassified

2 2 4 1

disease or irradiation, both of which are presently accepted as factors that predispose a person to osteogenic sarcoma. In two instances the patients noted tooth mobility prior to the onset of symptoms. In no case was any previous or concomitant organic disorder evident, with the exception of one patient in whom the tumor demonstrated rapid growth coinciding with two successivepregnancies prior to consultation. This tumor did not seem to progress between pregnancies. The average time that elapsed between the initial symptom and the first medical consultation was 3 months, excluding one case in which it was 3 years. No significant variation with respect to maxillary (3.3 months) or mandibular (2.7 months) location was observed.

to

The symptom most often associatedwith consultation, and present in every case, was an enlarging mass. The mean tumor size at the time of presentation was 5.3 X 4.5 cm with no notable variation according to site (5 X 5.2 cm in maxillary lesions and 4 X 5.5 cm in mandibular lesions, Table I). Other frequent symptoms included pain (four cases), oral mucosal ulceration (three cases), paresthesia of the area supplied by the infraorbital nerve (two cases), and tooth mobility (two cases).Only one patient had moderate elevation of serum alkaline phosphatase, but this was in a 13-year-old boy and thus was not considered significant. Other less specific symptoms were nasal obstruction, headache, diplopia, and trismus. No patient had pathologic fracture, local edema, or telangiectasia. Radiographic features. In six of the nine cases,the radiographic material was considered sufficiently adequate for diagnosis. Of these, three tumors were predominantly sclerotic in nature (Figs. 1 and 2), and three were mixed (Figs. 3 and 4). In no case was the so-called sunburst appearance noted. A symmetric widening of the periodontal space was not identified in any patient. In the absence of specific radiographic features suggestive of osteosarcoma, the radiologic impression was that of a primary bone tumor, with a cotton-like appearance and poorly defined margins. The destruction of cortical bone and extension into periosseoustissue were suggestive of malignancy (Fig. 3). Clinical diagnosis. The preoperative or clinical diagnosis was correct in only two of the nine cases.In the others, the original clinical diagnoses included granuloma (one case), epidermoid carcinoma (two cases), exostosis (one case), unclassified malignant

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Fig. 2. Hirtz radiograph of patient in Fig. 1 showing mixed pattern expanding lesion in right mandible.

tumor (one case), and chondrosarcoma (one case). No diagnosis was made for the remaining patient before biopsy. Pathology. Of the nine specimens obtained from radical excision, four were from the maxilla and the remainder from the mandible. Tumor size varied from 3 X 3 X 3 cm to 7 X 5 X 5 cm. The tissue was usually grayish in color and varied from soft to firm in consistency. Two tumors were cartilaginous. Histologically, all tumors fulfilled the criteria for the diagnosis of osteogenic sarcoma, that is, a malignant connective tissue proliferation with varying degrees of osteoid differentiation or osseoustrabeculae that can have cartilaginous foci or differentiation. According to the relative predominance of one component or another, these tumors are classified as fibroblastic, osteoblastic, or chondroblastic (Fig. 5). In four of our cases, the stromal component was predominant and was arranged in fascicles and swirls (Fig. 5, left). Two casesdemonstrated areas with the cytologic and structural characteristics of fibrous histiocytoma. Another two cases were identified as chondroblastic, with the cartilage assuming a lobular arrangement and more differentiated areas in the central zonesand greater cellular density and spindle morphology at the periphery (Fig. 5, center). One tumor was osteoblastic with abundant osteoid forma-

Fig. 3. Oblique radiograph showing mixed lesion of right mandibular body corresponding to osteogenic sarcoma, with characteristic extraosseous extension from angle into soft tissues.

tion (Fig. 5, right). The last two caseswere mixed, with equal proportions of the three components. The nine casesstudied were also classified according to the Broders index (Table II), which considers cellular density and degree of atypia. Use of this index showed that there were four Grade IV, two Grade III, and two Grade II lesions. None corresponded to Grade I. One tumor could not be classified. Treatment. Many of the patients reviewed received treatment, that included dental procedures and local surgery prior to being seen by our service. In two cases there had been multiple tooth extractions, and in another two there had been local excision of the visible tumor. In two cases, an unknown dose of preoperative irradiation had been applied. Radical resection was performed in eight of the nine cases treated at our hospital. The five patients with mandibular tumors were treated as follows: one curettage and hemimandibulectomy, one hemimandibulectomy with disarticulation and radical suprahyoid homolateral dissection, one hemi-

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Fig.

Oral August,

Surg. 1986

4. Mixed pattern of osteogenic sarcoma of incisor area of maxilla, displacing central incisor

Fig. 5. Histologic pattern of osteogenic sarcoma of maxilla and mandible. Fibroblastic (left), chondroblastic (center), and osteoblastic (right). (Hematoxylin and eosin stain. Magnification, ~63.)

mandibulectomy extending to adjacent soft tissue, and two extensive segmental mandibular resections. The four patients with maxillary tumors were treated as follows: three radical maxillectomies and one radical maxillectomy with orbital exenteration. Radiotherapy was employed as an adjunctive treatment in one caseof maxillary tumor to a total doseof 6000 rad; it was used as palliative treatment in one case. In no instance was radiotherapy used as a curative therapy or treatment of choice. Radical surgery alone or combined with irradiation was the treatment chosen for eight of the nine cases (89%), of which two patients have survived more than 10 years, four patients survived more than 5 years, and one patient died of disease. The overall survival of this group at 5 years was 85%. One patient who had surgery 2 months before submission

of this communication was not included in this group. The other patient who was treated by successive local resections and irradiation died of tumor after 3 years. The recurrence rate in our series was extremely low: only three cases(33%). Of these, one recurrence was in the maxilla and two were in the mandible. In the first case, the patient was originally treated by radical resection, which proved to be insufficient because of positive surgical margins. In the other two, the resection was incomplete. Of the three cases of recurrence, one patient was cured after additional surgery and survived 12 years. Of the two patients who died, only one had distant metastasis, diagnosed by sternal puncture. In both cases,death resulted from local invasion and involvement of the skull base. We could reach no significant

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conclusions regarding the relationship between tumor location and mortality, since one of our patients who died had a maxillary tumor and the other had a mandibular tumor. DISCUSSION

Osteogenic sarcoma of the maxilla and mandible is a relatively rare tumor, although more than 400 cases have been described in the world literature.le5 Nonetheless, our present knowledge of the tumor allows us to affirm that its clinical behavior and pathologic features differ markedly from those of its homologue in the long bones. Despite the limited number of cases in our series as compared with those of other studies,‘, 3-5we believe that this article makes a certain distinctive contribution to the present knowledge of these neoplasms. In this series, the osteogenic sarcomas affected mainly females, although in other larger series a small male prevalence has been observed, ranging between 63% at the Mayo Clinic4 and 52% at the New York Memorial Hospital5 The average age at appearance was principally in the fourth decade, the same as indicated in previous publications.‘-6 When the tumor is located in the long bones, occurrence in the second decade is most common. No relationship seems to exist between the maxillary or mandibular location of the lesion and the age at first appearance. Although Garrington3 found that maxillary tumors in his patients occurred at an earlier age than mandibular lesions, other series demonstrated the opposite. The maxillary/mandibular ratio presented no significant variation in our series (55.5% in mandible and 45.5% in maxilla), concurring with Clark and co-workers,4 although other series showed a prevalence of 3 : 2 to 2: 1 in favor of the mandibular tumors.3,6-yConversely, our series demonstrates maxillary sarcomas affecting females preferentially, and mandibular tumors being prevalent in males. In general, the publications reviewed establish no relationship between tumor location and sex of patient.4 The maxillary tumors showed a predilection for the most posterior portion of the alveolar process and the antrum. In most cases it was impossible to determine the site of origin of the lesion. The body was the part of the mandible most affected, followed by the angle, symphysis, and ascending ramus. In accordance with most published literature, the average interval between appearance of the initial symptoms and the first consultation is 3 months.‘*3*4’6-9 However, a case with 20-year evolution offered by Clark4 and one of 3-year evolution from our series illustrate the peculiar clinical behav-

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ior and slower growth rate of most of the osteogenic sarcomas of the maxilla and mandible. In agreement with published data, our results confirmed the varied clinical manifestations of these tumors. The appearance of a rapidly growing bone tumor, which is painless or only slightly painful, was the only constant finding in every patient. Other infrequent symptoms, such as edema and local paresthesias, seem to be caused by rapid tumor growth rather than being distinctive features of osteosarcoma. Not even significant elevation of serum alkaline of some long bone phosphatase, characteristic lesions, was present in our patients. As we described, specific radiologic interpretation is difficult because the radiographic appearance reported as typical in the literature was frequently not present. The sunburst pattern was not seen in any of our cases. This radiologic pattern may also appear in patients with metastatic carcinoma, myeloma, Ewing’s sarcoma, and tuberculosis and in some cases of osseous angioma.6 Symmetric widening of the periodontal ligament space, considered a highly suggestive early sign,” ‘O was not identified in any patient. Nonetheless, because this is an early sign in the development of these processes, appearing at about 6 weeks in the evolution according to Gardner,‘Oits absence in our series, with a mean evolution of 3 months, seems understandable. In summary, when interpreting radiologic findings, one should be guided more by the general criteria for malignancy than by criteria for specific tumors. The presence of a destructive unicentric lesion with poorly defined margins and a predominantly sclerotic, lytic, or mixed radiographic pattern should lead one to suspect an osteogenic sarcoma. The preoperative diagnosis of these neoplasms is often difficult. Their rarity in daily clinical practice and the lack of specific symptoms and radiologic findings can lead to equivocal or erroneous interpretations. Only histopathologic study of a biopsy specimen of the tumor will confirm a clinical diagnosis and guide definitive therapy. One of the most striking results of our review was the disagreement of our histologic findings with those of other authors. According to Clark and others,4 48% of the osteogenic sarcomas of the maxilla and mandible show a preponderance of chondroid differentiation, whereas in our patients this form represented only 25% of the total. However, the frequency in our series of the fibroblastic variety and the low expression of the osteoblastic type (12%), together with high survival, support Dahlin’s’ affirmation that the fibroblastic and chondroblastic types have a better prognosis. Finally, the distribution in our patients, according

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to Broders’ index, was similar to that observed in long bone osteosarcomas, with Grades III and IV predominating. This contrasts with the results of others1*4who assign a zero Syear survival to Grades III and IV tumors. From the perspective of our results, radical surgery is the treatment of choice and the only treatment that presently affords reasonable expectation of cure and is in agreement with other published material.3*4”’ In 1975, Pease” stated that microscopic extension of osteosarcoma of the maxilla and mandible cannot be determined by clinical or radiologic inspection. In agreement with this, our results showed that radical surgery is the best single therapeutic procedure and has the highest survival (85% of our series). For maxillary tumors, treatment should consist of radical maxillectomy with possible extension to neighboring tissues. In the mandible, hemimandibulectomy is the appropriate therapy for tumors of the ascending ramus. Wide resection, guided by intraoperative frozen sections of the surgical margins, seems to be the best procedure for parasymphyseal osteosarcomasor those in the body of the mandible. Finally, if palpable cervical nodes are present, neck dissection does apparently improve survival.3 Other alternatives, such as surgery and irradiation or radiation therapy alone, offer a much lower likelihood of survival, according to many studies.3B4’ ‘I, I2 However, since Jaffe et a1.13, I4 reported positive results after using high doses of methotrexate for treatment of osteosarcoma of the long bones, chemotherapy has become an important therapeutic adjunct. Recently, Rosen and co-workers,‘S using preoperative and postoperative chemotherapy combined with radical surgery, have reported a 90% recurrence-free period of 16 months on average in long bone osteosarcomas.I6Thus, the combination of preoperative and postoperative chemotherapy with delayed radical surgery used in the treatment of osteogenic sarcomas of the maxilla and mandible could probably improve the good results provided by radical surgery alone. Osteosarcoma of the maxilla and mandible does not usually produce distant metastasis, according to some.4”3 This is in disagreement with Garrington and colleagues,3who reported distant metastasis in approximately 50% of their cases.Even so, only one of our patients had extraregional spread. The main

Oral Surg. August, 1986

cause of death in this series was local recurrence and intracranial invasion. We conclude that osteogenic sarcoma of the maxilla and mandible is a malignant bone tumor with distinctive clinical, histologic, and prognostic characteristics that, when diagnosed and treated properly, may be curable in a large percentage of cases. REFERENCES I. Dahlin DC: Bone tumors, Spanish ed, Barcelona, Spain. 1969, Salvat Ed. 2. Spjut HJ, Dofman HD, Fechner RE, Ackerman LV: Tumors of bone and cartilage. Atlas of tumor pathology, Washington. 1970, Armed Forces Institute of Pathology. 3. Garrington GE, Scotield HH, Cornyn J, Hooker SP: Osteosarcoma of the jaws: analysis of 56 cases. Cancer 20: 377-39 I, 1967. Clark L, Unni KK, Dahlin DC: Osteosarcoma of the jaw Cancer 51: 231 l-2316, 1983. Huvos AC: Bone tumors: Diagnosis, treatment and prognosis, Philadelphia, 1979, W.B. Saunders Company. High CL: Osteosarcoma of the mandible: report of a cast. ORAL SURG ORAL MED ORAL PATHOL 45: 678-684,

1978.

Rota AN. Smith JL, Jing BS: Osteosarcoma and parosteal osteogenic sarcoma of the maxilla and mandible: study of 20 cases. Am J Clin Pathol 54: 625-636, 1970. 8. Curtis ML, Elmore JS, Sotereanos CC: Osteosarcoma of the jaws: report of a case and review of the literature. J Oral Surg 32: 125130, 1974. 9. Caron AS, Hajdu SI, Strong EW: Osteogenic sarcoma of the facial and cranial bones: a review of forty-three cases. Am J Surg 122: 719, 1971. 10. Gardner DC, Mills DM: The widened periodontal ligament ol osteosarcoma of the jaws. ORAL SURG ORAL MED ORAL PATHOL 41: 652-656,

1976.

I I. Pease CL, Maisel RS, Cantrell RW: Surgical management of osteogenic sarcoma of the mandible. Arch Otolaryngol 101: 761-762, 1975. 12. Chambers KG, Mahoney WD: Osteogenic sarcoma of the mandible: current management. Am Surg 36: 463-471. 1970. 13. Jalfe N: Recent advances in the chemotherapy of metastatic osteogenic sarcoma. Cancer 30: I627- I63 I. 1972. 14. Jaffe N, Frei E, Traggis D, et al: Weekly high-dose methotrexate-citrovorum factor in osteogenic sarcoma. Cancer 39: 45-50, 1977. IS. Rosen G, Marcove RC, Caparros B, et al: Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery. Cancer 43: 2163-2177, 1979. 16. De Vita VT Jr, Hellman S, Rosenberg SA: Cancer: principles and practice of oncology, Spanish ed. Barcelona, Spain, 1984, Salvat Ed, pp. 994-1009. Reprint

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Dr. B. Colmenero C.S. “La Paz” Servicio de Cirugia Maxilofacial Av da Castellana, 261 28034-Madrid, Spain