Radiation-Induced Osteosarcoma of the Temporal Bone

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1 台灣癌症醫誌 (J. Cancer Res. Pract.) 28(3), , 2012 Case Report journal homepage: Radiation-Induced Osteosarcoma of the Temporal Bone Yung-Hsin Hsu 1,4, Shih-Ming Jung 5, Wen-Cheng Chang 6, Yeng-Chung Chang 1,2,3 * 1 Institute of Molecular Medicine, National Tsing Hua University, Hinchu, Taiwan 2 Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hinchu, Taiwan 3 Department of Life Science, National Tsing Hua University, Hinchu, Taiwan 4 Department of Neurosurgery, Chang Gung Memory Hospital and Chang Gung University, Taoyuan, Taiwan 5 Department of Pathology, Chang Gung Memory Hospital and Chang Gung University, Taoyuan, Taiwan 6 Department of Hematology-Oncology, Chang Gung Memory Hospital and Chang Gung University, Taoyuan, Taiwan Abstract. A 32-year-old female suffered from a bulging mass over the right temporal area 4 years after radiotherapy for intraventricular neurocytoma. Computed tomography and magnetic resonance imaging revealed an osteolytic lesion over the right temporal bone. The patient underwent a craniotomy procedure for resection of the tumor, and the histological diagnosis was osteosarcoma. Postoperative adjuvant chemotherapy was administered. However, local recurrence developed 8 months later, and the patient again underwent surgical resection and chemotherapy. Though aggressively treated, the patient deteriorated due to local recurrence and lung metastasis, and she died 14 months after the diagnosis. Ultimately, radiation-induced osteosarcoma of the skull bone is a rare complication of radiotherapy for brain tumor, with a generally poor prognosis. 病例報告 Keywords : radiation-induced sarcoma, skull tumor 放射線引發之骨肉瘤 許永信 1,4 容世民 5 張文震 6 張兗君 1, 2, 3 * 1 清華大學分子醫學所 2 清華大學奈米工程與微系統所 3 清華大學生命科學系 4 長庚醫院神經外科 5 長庚醫院病理科 6 長庚醫院血液腫瘤科 中文摘要 32 歲女性,4 年前曾因腦室神經細胞瘤接受放射治療, 發現右顳部腫起 腦部電腦斷層及核磁共振都顯示右顳骨蝕骨性之腫塊 病患於是接受開顱手術切除腫塊, 病理切片顯示為骨肉瘤 術後, 病患接受化學治療 但是, 八個月後出現局部復發, 病患再次接受開顱手術及化學治療 雖經積極治療, 病患又再出現局部復發及肺部轉移 病患於診斷 14 個月後死亡 顱骨之放射線引發骨肉瘤, 乃腦瘤放射治療, 罕見且預後極差之併

2 Y. H. Hsu et al./jcrp 28(2012) 發症 關鍵字 : 放射線引發之骨肉瘤 顱骨腫瘤 INTRODUCTION Radiotherapy is the standard treatment for many brain tumors. Unfortunately, it may induce undesirable late complications, such as radionecrosis and secondary tumors. Osteosarcoma is a highly malignant tumor and mainly occurs in the long bones in adolescents and young adults. Craniofacial sarcoma accounts for less than 10 % of all osteosarcoma [1,2], where patients tends to be older and the prognosis is more favorable than for patient with long bone osteosarcoma. However, radiation-induced osteosarcoma is different. Unlike primary craniofacial osteosarcoma, radiation-induced craniofacial osteosarcoma usually has a less favorable prognosis. We present a patient who was first 28-years-of-age when initially seen at our hospital and treated with radiotherapy for intraventricular neurocytoma, who returned 4 years later with diagnosed osteosarcoma of the right temporal bone. CASE REPORT A 28-year-old female was first admitted to our hospital in January 2004, with symptoms of progressive headache and blurred vision for months. An MRI of the brain showed a large tumor over the right lateral ventricle and apparent hydrocephalus. The patient underwent a craniotomy procedure for removal of the intraventricular tumor and placement of a ventriculo-peritoneal shunt. After further tissue sample testing, the histological diagnosis was central neurocytoma. After surgery was completed, the post-operative *Corresponding author: Yen-Chung Chang M.D. * 通訊作者 : 張兗君醫師 Tel: Fax: ycchang@life.nthu.edu.tw course of treatment was uneventful. She then received radiotherapy with 54 GY in 27 fraction. She was in good condition and receiving regular follow- up at our outpatient department. Annual brain MRI follow-up showed no tumor recurrence (Figure 1). In February 2008, at the age of 32, she suffered from swelling over the right temporal area. Her physical and neurological examinations were normal, except for the presence of an unmovable mass, 2 x 2 cm in size, underneath the right temporal scalp. CT and MRI of the brain (Figure 2) showed an osteolytic lesion over the right temporal bone. A right temporal craniotomy procedure was performed, during which a firm mass arising from temporal bone and the resultant destruction of the temporal bone were noted. However, the overlying scalp and underlying dura remained intact, and the mass and the involved bony structure were totally removed. The histological diagnosis was osteosarcoma (Figure 3), wherein tissue examination showed spindle-shaped tumor cells with widespread nuclear pleomorphism, and numerous signs of mitoses. After surgical removal of the tumor, the patient underwent 3 courses of chemotherapy with intravenous Adriamycin. Thereafter, the post-operative period and chemotherapy courses were uneventful, and no evidence of tumor progression was present at the patient s monthly follow-up. In October 2008, 8 months after the first right temporal craniotomy, the tumor recurred with swelling over the right temporal area. So, a second operation with more extensive resection was immediately undertaken. Subsequent to surgery, the patient underwent 5 courses of chemotherapy with IVP (ifosfamide, etoposide, and cisplatin). Despite two operations and several courses of chemotherapy, further recurrence with extension to the sphenoid ridge (Figure 4), and eventually distant me-

3 136 Y. H. Hsu et al./jcrp 28(2012) Figure 1. Post-op 2 years MRI follow-up showed no bony tumor, only previous craniotomy. (A) T1WI with enhancement, axial view. (B) T1WI with enhancement, coronary view Figure 2. Computed tomography scan showed skull bone mass with bony erosion (A). Brain magnetic resonance T1-weighted image with gadolinium enhancement revealed bony tumor outside the dura (B)

4 Y. H. Hsu et al./jcrp 28(2012) Figure 3. The photomicrography of the resected tumor showed interlacing bundles of spindle-shaped cells (A) (H & E, x200). Nuclear pleomorphism, hyperchromasia, and numerous mitoses were also found (B) (H & E, x400) tastasis to the lung developed. The patient was then transferred to a local hospital, where she died 2 months later. DISCUSSION The occurrence of malignancy in the irradiated field is a rare but well-documented long-term complication of radiotherapy. The first reported case was a squamous cell carcinoma arising in the hand of a X-ray technician in Radiotheary on the head has been proposed to be associated with the developments of glioma [3], meningioma [4], and sarcoma [5]. The estimated incidence of radiation-induced sarcoma is 0.03% to 0.22% [6,7]. The development of sarcoma after radiation is associated with the cumulative dose of radiotherapy given during extended treatment. In general, a minimal radiation dose of 30 Gy is required for radiation-induced sarcoma to develop. The reported radiation doses involved in customary radiotherapy vary from 50 Gy to 60 Gy [5,8]; our patient received 54 Gy. The latency period between radiotherapy and the development of sarcoma ranged from 4 to 15 years, with a mean interval of 9 years [9]. However, a latency period as short as 2 years has been reported [10]. In our case, osteosarcoma developed 4 years after radiotherapy was administered. As Cathan et al. [8] had earlier mentioned, the diagnosis of radiation-induced sarcoma must fulfill 4 prerequisites: (1) There must have been roentgenographic evidence of the non-malignant nature of the initial bone condition; (2) sarcoma must develop on the previously irradiated field; (3) a relatively long latent period must have elapsed between irradiation and the appearance of sarcoma; and (4) the sarcoma must have been pathologically proven. After review of these criteria, our case fulfilled these requirements. Osteosarcoma typicallys occurs in the differing arenas of the long bones, so cases of cranial osteosarcoma are rare. Various predisposing factors of cranial osteosarcoma have been proposed, including Paget s disease, fibrous dysplasia, retinoblastoma, Li-Fraumeni syndrome, and previous irradiation. Even though the trigger mechanism of radiation-induced sarcoma is apparent, the actual pathogenesis of radiation-induced sarcoma remains unknown. Patients with retinoblas-

5 138 Y. H. Hsu et al./jcrp 28(2012) Figure 4. Brain magnetic resonance T1-weighted images with gadolinium enhancement showed extension of tumor to sphenoid bone and orbital wall during later stage (A, B) toma have an increased risks to develop sarcoma, particularly after radiotherapy [11]. Patients with Li- Fraumeni syndrome, which is among the germ-line p53 gene mutations, are at a higher risk of radiation-induced sarcoma [12,13]. RB 1 and p53 gene mutation are common among patients with radiation-induced sarcoma, suggesting that the mutation on tumor suppressor genes might play a crucial role in tumor development [14]. Cranial osteosarcoma usually presents as a growing mass beneath the scalp, which is sometimes tender and painful. The tumor mainly arises from the skull, and rarely from the meninges. In our case, the patient suffered from a painless growing mass, with intact dura. Craniofacial osteosarcoma is different from long bone osteosarcoma because a typical patient is older so the tumor tends to be lower grade, with infrequent distant metastasis and a better prognosis. However, the radiation-induced craniofacial osteosarcoma has distinct clinicopathological features. Compared to primary craniofacial osteosarcoma, radiation-induced osteosarcoma tends to be a high grade tumor, more aggressive and having a poor prognosis [15]. Our case showed repeated local recurrence, eventual lung metastasis, and ultimately an unfavorable outcome. The treatment of choice for osteosarcoma is complete surgical resection with negative margin. Surgery and chemotherapy have been used in combination to treat primary craniofacial osteosarcoma [16]. However, in cases of radiation-induced cranial osteosarcoma, the tumor grows rapidly intracranially and extracranially, with invasion into many vital structures. Complete resection is not possible because of involvement of the skull base and these other vital structures. Any additional survival benefit associated with adjuvant chemotherapy for radiation-induced osteosarcoma has not been established. CONCLUSIONS Skull radiation-induced osteosarcoma is a serious late complication of radiotherapy for brain tumors. Relative to primary skull osteosarcoma, radiation-

6 Y. H. Hsu et al./jcrp 28(2012) induced osteosarcoma is more aggressive, recurs more frequently, and has a more unfavorable prognosis. It is critically important that postradiation patients should have long-term follow-up, and in case of osteosarcoma occurrence, more extensive excision should be undertaken during surgery. REFERENCES 1. Clark JL, Unni KK, Dahlin DC, et al. Osteosarcoma of the jaw. Cancer 51: , Junor AT, de Abreu Alves F, Pinto CA, et al. Clinicopathological and immunohistological analysis of twenty-five head and neck osteosarcoma. Oral Oncol 39: , Linwicz BH, Berger TS, Linwicz RG, et al. Radiation associated gliomas: a report of four cases and analysis of post-radiation tumors of the central nervous system. Neurosurgery 17: , Mack EE, Wilson CB. Meningioma induced by high dose cranial irradiation. J Neurosurg 79: 28-31, Chabchoub I, Gharbi O, Remadi S, et al. Postirradiation osteosarcoma of the maxilla: a case report and current review of literature. J Oncol 2009: , Amendola BE, Amedola MA, McCltchey KD, et al. Radiation associated sarcoma: a review of 23 patients with postradiation sarcoma over a 50-year period. Am J Clin Oncol 12: , Kohn HI, Fry F JM. Medical progress: radiation carcinogenesis N Engl J Med 310: , Cathan W, Woodward H, Higinbotham N, et al. Sarcoma arising in irradiated bone: report of 11 cases. Cancer 28: , Chang SM, Barkr FG, Bollen AW, et al. Sarcoma subsequent to cranial irradiation. Neurosurgery 36: , Murray EM, Werner D, Greeff FA, et al. Postradiation sarcoma: 20 cases and a literature review. Int J Radiat Oncol Biol Phys 45: , Kleinerman RA, Tucker MA, Tarone RE, et al. Risk of new cancers after radiotherapy in long term survivors of retinoblastoma. J Clin Oncol 23: , Heymann S, Delaloge S, Rahal A, et al. Radioinduced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome. Radiat oncol 5: , Gonin-Laurent N, Gibaund A, Huygue M, et al. Specific TP 53 mutation pattern in radiationinduced sarcoma. Carcinogenesis 27: , Gonin-Laurent N, Hadj-Hamou NS, Vogt N, et al. RB 1 and TP 53 pathways in radiation-induced sarcoma. Oncogene 26: , Mchugh JB, THomas DG, Herman JM, et al. Primary versus radiation-associated craniofacial osteosarcoma. Cancer 107: , Patel SG, Meyers P, Huvos AG, et al. Improved outcomes in patients with osteogenic sarcoma of head and neck. Cancer 95: , 2002.