A case of multiple-site osteosarcomas in the jaw of a 56-year-old patient is reported. The disease occurred consecutively at three different sites (left maxilla, left mandible, right mandible) separated by time intervals of 12 and 18 months, respectively. Metachronous osteosarcomas of the long bones is a rare form of osteosarcoma and implies multiple lesions appearing at different times, each one behaving clinically as a primary lesion. The pathogenesis of this disease is unknown as it is unclear whether the lesions represent independent primary tumours or metastatic disease.
Primary osteosarcoma of the jaw is rare and represents approximately 6–7% of all primary osteosarcomas . The mandible is involved more commonly than the maxilla (1.5:1 to 2:1 ). It usually presents with a painless swelling, mucosal ulceration and paraesthesia. Most of the data on these tumours are obtained from retrospective studies .
According to the 2002 WHO classification , osteosarcoma is ‘a primary malignant tumour characterized by the direct formation of bone or osteoid by the tumour cells’. There are three main histological types including the osteoblastic, chondroblastic and fibroblastic variants, with the matrix being composed of bone and/or osteoid, chondroid and collagen in each type, respectively. B ennett et al. report that osteosarcomas of the jaw often show little cellular atypia and metastasize late. Control of local spread of the disease remains the main goal of treatment with surgical resection of the tumour.
Multiple-site osteosarcomas have been classified as multicentric/synchronous and metachronous and it is imperative to search for additional skeletal lesions when a patient is diagnosed with osteosarcoma.
Multicentric (synchronous multifocal) osteosarcomas are defined as lesions arising simultaneously, or within 6 months, of one another at more than one site in the absence of pulmonary metastases . B acci et al. suggest that the histological homogeneity of multiple osteosarcoma in a large proportion of the primary and secondary lesions, implies a mechanism of bone-to-bone metastasis from a single tumour.
Metachronous osteosarcomas are defined as multiple lesions appearing at different times, each one clinically behaving as a primary lesion .
Osteosarcomas of the jaw bones present and behave differently to those of the long bone . They occur more often in elderly patients, are more often of the chondroblastic type and survival rates are better because most are of low-grade malignancy. The authors are not aware of any published report on patients presenting with multiple-site metachronous osteosarcoma of the jaws. This case is the first to report the management of a patient with two metachronous lesions presented consecutively in the left mandible and right mandible following treatment of non-metastatic primary osteosarcoma of the left maxilla.
A 56-year-old Caucasian female was initially referred in 2003 with a tumour in her left maxilla. Her medical history was non-significant including only Sjogren’s syndrome. The patient has been a non-smoker with little alcohol consumption. In July 2003 she underwent a radical resection of the maxillary tumour and simultaneous reconstruction with a composite osseous deep circumflex iliac artery and internal oblique muscle flap. Histopathology showed infiltration of the maxillary bone plate extending into palatal mucosa and premaxillary soft tissues. The margins were clear albeit close laterally (3 mm) and superiorly (1 mm). The tumour was reported as ‘of immature cartilage with moderate cytological atypia and scattered mitoses’ and it was diagnosed as a mesenchymal chondrosarcoma with moderate maturation.
Two months later in September 2003 the free-flap failed and was removed. During the same procedure, further excision of the histologically ‘close’ superior margin was carried out, which was shown to be clear of tumour. Flap failure was attributed to vascular thrombosis, which was not recognized initially, as monitoring of flaps without a skin component in areas with difficult access, such as the posterior maxilla, is sometimes problematic. No further reconstruction was attempted at the time and the patient received an obturator. Adjuvant therapy was not recommended due to histological clearance.
In July 2004, the patient underwent extraction of a left mandibular molar, which was followed by abscess formation and subsequent development of frank tumour in the socket. She immediately had a PET-CT scan which showed intense fluorodeoxyglucose (FDG) uptake within the central portion of the left mandible. In addition, a 1 cm left submandibular node showed moderate FDG uptake. On CT there was evidence of a small irregular radiolucency in the left mandible. The tumour was infiltrating the mandibular bone, but no pulmonary or mediastinal metastatic disease was present.
The treatment consisted of left hemi-mandibulectomy and left neck dissection (Levels I–IV) with simultaneous reconstruction with a fibula free-flap. Histologically all lymph nodes were tumour free. The pathology of the mandibular tumour was reviewed by experts in Glasgow (UK) and in the Mayo Clinic (USA) in association with the pathology of the initial maxillary tumour. It was suggested that the original maxillary tumour was likely to be a chondroblastic osteosarcoma, although osteoid was scant and overall diagnosis difficult. The left mandibular tumour was diagnosed as a (chondroblastic) osteosarcoma, of higher grade than the original maxillary tumour, with evidence of sheets of primitive cells resembling those of the original lesion. A number of pleomorphic cells were identified that were not consistent with a mesenchymal chondrosarcoma, which had been the original diagnosis of the primary maxillary lesion.
In December 2004, the patient was referred to the Department of Oncology, University College London Hospital, for adjuvant chemotherapy (doxorubicin and cisplatin). In January 2005, she was diagnosed with local tumour recurrence superficial to the middle aspect of the fibular flap in her left (reconstructed) neo-mandible, which was confirmed with biopsy as a high grade chondroblastic osteosarcoma ( Fig. 1 ). She continued with chemotherapy with cisplatin being replaced by carboplatin because of renal impairment. Chemotherapy was completed in May 2005 and she immediately underwent resection of the left fibula neo-mandible up to the right premolar region. Histology demonstrated negative margins. The newly created defect was reconstructed with a second vascularized composite fibula flap ( Fig. 2 ) followed by radiotherapy (50 Gy), completed in November 2005. The patient remained disease free for 1.5 years.