Ⅰ. INTRODUCTION

Osteosarcoma(OS) is a high-grade sarcoma in which the tumor cells produce bone.⁽¹⁾ Telangiectatic osteosarcoma( TAEOS) is a rare subtype of OS composed of blood-filled or empty cystic architecture simulating aneurysmal bone cyst.⁽¹⁾ TAEOSs are rare, accounting for 2-12% of all OSs.⁽²⁾ According to the recent large population-based cohort analysis using the Surveillance, Epidemiology and End Results (SEER) registry, TAEOSs account for 3.1% of all OSs.⁽³⁾ Compared to conventional osteosarcoma(COS), TAEOS patients are younger than COS patients.(the mean age at diagnosis was 23,5 and 29.4, respectively)⁽³⁾ TAEOSs of the jaws are also uncommon, accounting for 2.2% of all TAEOSs.⁽⁴⁾ Three cases of primary TAEOS in mandible have been reported.^(5–7) To the best of my knowledge, this is the fourth case of primary TAEOS of the mandible.

Ⅱ. CASE REPORT

A 36-year-old female who had been previously diagnosed with osteosarcoma by biopsy reported with a chief complaint of throbbing and swelling of the right mandible. Panoramic radiograph showed ill-defined, destructive, expansile lesion involving almost all right mandibular body.(Fig.1A) Therefore, the treatment plan of neoadjuvant chemotherapy followed by wide surgical resection and adjuvant chemotherapy was made.

Before surgery, the patient received neoadjuvant chemotherapy composed of cisplatin, doxorubicin, and high-dose methotrexate. After chemotherapy, radiographic images showed increasing lesion, anteriorly to symphysis, posteriorly to retromolar trigone area, suggesting little response to neoadjuvant chemotherapy.(Fig. 1A,1B) Enhanced CT images showed the largest dimension of the lesion before neoadjuvant chemotherapy was about 4.5 cm.(Fig. 1C) After the neoadjuvant chemotherapy, that of the lesion became about 5.5 cm.(Fig. 1D) Interestingly, T2-weighted MR image showed fluid-fluid level.(Fig. 1E) No significant metastatic lymph node was found.

Hemi-mandibulectomy and selective neck dissection were performed for the lesion. On serial section along the tumor, small or large cystic spaces with focal whitish solid mass were found. There were some hemorrhages in the cystic space, constituting about less than 10%. The ratio of cystic spaces and white to tan solid mass is about 50/50. No obvious necrosis was observed. On palpation of the cut surfaces, the calcified materials were faintly felt, but not obvious.

Histopathological evaluation of the mass revealed blood-filled, multicystic spaces with anaplastic tumor cells and multinucleated giant cells.(Fig. 2A) Tumor cells composed of pleomorphic cells with hyperchromatic nuclei,anaplastic spindle cells or neoplastic cells forming osteoid or cellular disorganized bone.(Fig. 2B,2D) Abnormal mitosis was also observed.(Fig.2D) Mitotic rate (mitotic figures per 10 high-power filed; x400) was about 1. Microcystic space was separated by septum composed of multinucleated giant cells and anaplastic tumor cells.(Fig.2C) Necrosis was not significant, less than 3% of entire tumor areas. Taken together, the final diagnosis of telangiectatic osteosarcoma was made.

Tumor size was AP 8.6 x ML 1.9 x SI 2.9 cm. no regional lymph node metastasis was found. According to the AJCC cancer staging manual, mitotic count score was 1 and necrosis score was 1.(8) TNM stage was ypT2pNOcM0pG3. (Stage ⅡB) Tumor cells were not just gently remodeling the surrounding bone, but also infiltrating of the bone, resulting close resection margins with some areas. Clear surgical resection margins were confirmed except the distance between tumor and inferior surgical margin. (less than 0.1 cm)

After surgery, patient received adjuvant chemotherapy composed of ifosfamide, carboplatin and etoposide. The patient is free of disease for 6 months after surgery.

Ⅲ. DISCUSSION

Our patient was diagnosed with osteosarcoma by biopsy at the hospital before being transferred. Histopathological findings suggesting TAEOS were not found on biopsy, it seems that solid mass area of our patient`s tumor have been reflected.

Previous article suggested that TAEOS has a worse prognosis than conventional osteosarcoma(COS).(9) but other articles have been suggesting there are no differences in overall survival between them.(3,10,11) As of now, It seems that overall survival of TAEOS is similar to that of COS.(1) TAEOSs frequently develop around knee (~60%) and in the proximal humerus (~20%).(2) It has male predominance similar to that of COS.(4)

Excluding distant metastasis from primary lesion(12), three cases of primary TAEOSs in the jaws have been reported in English literature.(5–7) To the best of my knowledge, this is the fourth case of primary TAEOS of the jaws.(Tab. 1) The mean age is 18.3 years, lower than the previous recent study by Xu, M.(3) All of the four TAEOSs arose in the mandible. There has been no report of TAEOS affecting maxilla. Swelling was the most common chief complaint followed by tenderness and throbbing. Except for one case(7), not reported surgical history, All three patients received hemi-mandibulectomy, but adjuvant or neoadjuvant therapy varied from patient to patient. It is well known that some genetic syndromes including Li-Fraumeni syndrome, hereditary retinoblastoma(1) are related to increase the incidence of OS. But there was no patient with such genetic history. Although the patient with extragnathic TAEOS frequently shows pathologic fracture,(1,2,13) no patient who experienced pathologic fracture was found.

The diagnosis of TAEOS was based on the criteria according to WHO classification of tumors.(1) These criteria are 1) bone tumor with compatible imaging; bone production by tumor cells; permeative and destructive growth pattern, 2) blood-filled or empty cystic spaces separated by fibrous septa, 3) Tumor cells with high-grade atypia. 1) and 2) are essential and 3) is desirable.

The present case radiographically showed aggressive bone destruction of the mandible, anteriorly to symphysis, posteriorly to retromolar trigone. (Fig.1A-D) Although there was no evident periosteal reaction, eg. sun-ray appearance or codman triangle which is common in osteosarcoma(13), T2-weighted MR image showed fluid-fluid level, which is one of the characteristic features of TAEOS.(Fig.1E)(13)

In histopathological evaluations, evident but minimal periosteal reaction was found, suggesting that it was not prominent enough to show the CT or MR imagings. Clear surgical resection margins except the inferior surgical margin were confirmed. In the area of close resection margin, tumor cells invaded through the cortical bone, resulting unexpected surgical resection margin. Thus, it is worth considering surgical resection with wide margins when surgical planning.

In the present case, the tumor was differentiated from aneurysmal bone cyst (ABC), central giant cell granuloma (CGCG) and conventional osteosarcoma (COS). On MR imaging, ABC has limited thin peripheral septa (usually 2-3 mm thick). On the other hand, TAEOS has relative thick septa around the hemorrhagic spaces.(14) The presence of an osteoid matrix within nodular or septa region is a second distinguishing feature from ABC at CT image.(14) Histopathologically, TAEOS differs from ABC in having frankly sarcomatous cells with atypical mitosis, despite their similarities at the radiologic and macroscopic levels.(15,16) CGCG sometimes has histologic features of fibrous septa with osteoid deposition or woven bone formation.(14) But CGCG does not show large cystic space.(6) In the present case, focal solid mass area showed anaplastic tumor cells forming osteoid, which is also found in COS.(17) But blood-filled large cystic space with sarcomatous cells, occupying most of the lesion helps to diagnosis.

TAEOS is treated with neoadjuvant chemotherapy, surgical resection followed by adjuvant chemotherapy. Chemotherapeutic agents of TAEOS are similar to those of COS(18), which include cisplatin, carboplatin, methotrexate, doxorubicin and ifosfamide.(18) It is recommended that at least two of them need to be included.(18) It is well known that TAEOSs are better response to chemotherapy compared to COSs(10) and poor response to neoadjuvant chemotherapy is related to poor outcome.(1)

The prognosis of OS is influenced by histological response to neoadjuvant chemotherapy, tumor stage, anatomical location, and adequate surgical resection margins.(19– 23) A good response to neoadjuvant chemotherapy is defined as more than 90% necrosis, suggesting that out patient was little response to chemotherapy.(20)

Telangiectatic osteosarcoma is a rare malignant bone forming tumor mimicking other benign entities, such as aneurysmal bone cyst and central giant cell granuloma.(16) Thus, careful diagnosis through thorough radiographic and histopathologic evaluation is important to establish a treatment plan, prognosis, prediction and management strategy.