Synchronous multicentric osteosarcoma (SMO) is rare with fewer than 100 well-documented cases in the medical literature. SMO affecting the jaw is even rarer with only three cases involving the mandible having been reported. SMO in the maxilla has not been previously reported. The authors report the first case of SMO involving both mandible and maxilla in an 18-year-old girl. The clinical course, radiological and histological appearance of the lesion indicated it was an SMO rather than metastasis arising from a single osteosarcoma. This case could be regarded as powerful evidence to support the multicentric theory related to SMO.
Synchronous multicentric osteosarcomas (SMO), defined as more than one bone lesion at presentation, is a rare form of osteosarcoma. It accounts for 1–3% of total osteosarcomas . Osteosarcomas account for only 5% of all malignant tumors occurring in the maxilla and mandible , so one lesion involving the jaw in a case of SMO is rare. Until now, only three cases of SMO involving the mandible have been reported in the English literature . A case of SMO involving the maxilla has not been previously documented (MEDLINE 1966–2009). The authors present a case of SMO involving mandible and maxillas in an 18-year-old girl.
An 18-year-old Chinese girl was referred for right facial swelling. The patient noticed a painless swelling of the right face and enlarged left mandible in June 2009, 1 month later he presented for treatment. The patient’s first right maxillary molar had been extracted because of caries at 12 years of age; there was no other contributory past medical or familial history such as trauma or radiation. Extraoral examination revealed facial asymmetry related to the enlargement of the right maxilla and the left lateral mandible. The left swelling extended from the zygomatic arch to the inferior border of the mandible, and the overlying skin was normal and nonindurated.
Owing to the swelling of right maxilla, the eyes were not at the same horizontal plane. Intraoral examination showed there was a mass measuring 2.5 cm × 2.0 cm on the buccal gingiva of the maxillary teeth, which was bony-hard and reddish in color. The buccal cortex over the left mandibular molar region was also enlarged. There was no abnormal finding in the cervical lymph nodes or any other part of the body. The serum alkaline phosphatase level was 299 U/l (normal range 20–150 U/l) and the calcium level was 2.22 mmol/l (normal range 2.25–2.75 mmol/l). These two laboratory tests suggested the problem was a bone disease. There was no abnormality in any other serum chemistry or hematology tests. A panoramic radiograph revealed four mixed radiolucent and radiopaque lesions with poorly circumscribed borders in the maxillas and mandible. The first lesion of the left mandible showed bone expansion and a radiographic ‘sun-ray’ pattern.
The second, involving almost the entire left maxilla, was mainly radiolucent on radiography. The third was in the right maxilla molar region and showed sclerotic manifestation ( Fig. 1 ). The fourth in the right mandibular molar region was not apparent, but computed tomography (CT) clearly detected a heterogeneously sclerotic lesion ( Figs. 1 and 2 ). All lesions showed similar radiological sclerotic appearance with no clear borders in CT ( Figs. 2 and 3 ). A chest radiograph, CT scanning of the cerebral cranium and abdominal ultrasound examination were normal.
Biopsy of the right maxillary and left mandibular swellings was performed. Microscopic examination showed round to oval, spindle-shaped cells with pleomorphic hyperchromatic nuclei, prominent nucleoli, and large foci of irregular, dense, basophilic osteoid matrix ( Fig. 4 ). The pathological examination confirmed two biopsy tissues were osteoblastic osteosarcomas. Though the patient was told of the poor prognosis, she and her parents refused any further treatment and she died 4 months later.
Osteosarcoma is the most common malignant tumor of bone. In unusual conditions, the disease can affect multiple bone sites at the same time (synchronous) or at varying intervals (metachronous) . The metachronous type is more common than the synchronous (SMO). The latter tends to occur in childhood or early adolescence and is almost invariably sclerotic both radiologically and histologically. Recent reports suggest a poor prognosis despite advances in surgery and chemotherapy .
The synchronous type principally involves long bones in a symmetric distribution. In contrast to the metachronous type in which lesions favor the axial skeleton, such as the pelvis, spine, shoulder girdle, skull, synchronous lesions usually occur in typical osteosarcoma locations, often involving distal femur, proximal tibia or humerus . A case of SMO with one lesion affecting the mandible or maxilla is rare. No case involving the maxilla has been documented in the literature (MEDLINE 1966–2009). Only three cases involving the mandible have been reported in the English literature .
The three reported cases occurred in younger patients with a median age of 16 years (15, 16, 17 years, respectively) . The patient presented here was 18 years old. SMO occurs earlier than ordinary head and neck osteosarcoma, which occurs most commonly in the third and fourth decades . Whether this tumor represents a true multifocal primary osteosarcoma or an aggressive metastatic spread of a unifocal osteosarcoma remains under debate .
It has been suggested that multicentric osteosarcoma is probably due to metastatic disease and not multiple synchronous primary lesions based on the following findings. First, most of these patients have one dominant tumor. Second, bone metastasis is not rare in ordinary osteosarcoma. Third, bone metatasis via venous channels cannot be excluded . Bone-to-bone metastases could occur via a similar mechanism as in prostate cancer via Batson’s venous plexus, or intraosseous embolization through marrow sinusoids. Fourth, the response to chemotherapy of ‘primary’ and ‘secondary’ lesions was always similar and this homogeneity supports the thesis that SMO represents bone-to-bone metastases from a monocentric tumor .
The multicentric theory of SMO is supported by many authors, because there is no obvious route for spread if the lungs are free of tumor, which is thought to rule out hematogenous metastasis.
Osteosarcoma of the mandible metastasizing to the maxilla, or vice versa, is extremely rare. Theoretically, there is no apparent metastatic channel from mandible to maxilla or from maxilla to mandible. The case presented here is characterized by simultaneous involvement of multiple jaw sites, including the maxillas and mandible. Panoramic radiography and CT revealed four mixed radiolucent and radiopaque lesions with poorly circumscribed borders in both sides of the maxilla and mandible without a dominant lesion. The lesions were basically symmetric.
If this was a case of osteosarcoma with multifocal metastases, it would be difficult to differentiate the primary lesion. Although a bone 9mTc scintigram was not performed owing to the patient’s economic condition, chest radiography, CT scanning of the cerebral cranium and abdominal ultrasound examinations and physical examination excluded the possibility of lesions at other sites, especially the lung. The clinical course, the radiological and histological appearances of the osseous lesions (with the absence of an apparently dominant lesion), early occurrence and poor prognosis suggest the lesions are multiple primary osteosarcomas, rather than secondary deposits arising from a single osteosarcoma. The authors consider the case might be powerful evidence to support the multicentric theory.
The patient did not have known predisposing factors such as Paget’s disease of the bone or exposure to radiation, nor proposed predisposing conditions such as fibrous dysplasia and trauma. Prognosis for SMO is invariably poor with a rapidly fatal clinical course , as in this case. The differences in age distribution and poor prognosis suggest SMO could be a different entity from ordinary osteosarcoma and the etiology might be also different. The perspectives for understanding the biology of this neoplasm might be based on molecular biology and genetic studies of multiprimary osteosarcoma cell lines. Previous reports have shown that SMO patients have a very high incidence of somatic and germ-line p53 mutations, thus strongly implicating the importance of this gene in the pathogenesis of multifocal osteosarcoma . Molecular analysis, including gene examination, might be useful in differentiating SMO from metastatic spread of a unifocal osteosarcoma.