Year : 2009 | Volume
: 20 | Issue : 3 | Page : 380--384
Radiation-induced spindle cell sarcoma: A rare case report
Mubeen Khan, Rupa Chandramala, Ridhima Sharma, KR Vijayalakshmi
Departments of Oral Medicine and Radiology, Government Dental College and Research Institute, Bangalore - 560 002, India
Departments of Oral Medicine and Radiology, Government Dental College and Research Institute, Bangalore - 560 002
Ionizing radiation has been known to induce malignant transformation in human beings. Radiation-induced sarcomas are a late sequel of radiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gray (Gy) and above, with a dose ranging from 16 to 112 Gys. Spindle cell sarcomas, arising after radiotherapy given to treat the carcinoma of head and neck region is a very uncommon sequel. This is a rare case report of spindle cell sarcoma of left maxilla, in a 24-year-old male, occurring as a late complication of radiotherapy with Cobalt-60 given for the treatment of retinoblastoma of the left eye 21 years back.
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Khan M, Chandramala R, Sharma R, Vijayalakshmi K R. Radiation-induced spindle cell sarcoma: A rare case report.Indian J Dent Res 2009;20:380-384
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Khan M, Chandramala R, Sharma R, Vijayalakshmi K R. Radiation-induced spindle cell sarcoma: A rare case report. Indian J Dent Res [serial online] 2009 [cited 2019 Jun 24 ];20:380-384
Available from: http://www.ijdr.in/text.asp?2009/20/3/380/57366
Radiation-induced sarcomas (RIS) are well-known and late sequelae of radiation therapy which often escape early detection and timely intervention, thereby, rapidly leading to early demise of afflicted patients. 
A 24-year-old blind man reported with the complaint of a swelling in his upper left jaw, since one- and- a-half months. A history of the present illness revealed that he had left nasal discharge and difficulty in breathing through the left nostril, followed by a swelling in the upper left jaw, which was neither associated with pain nor bleeding. The swelling slowly progressed to attain the present size. There was mobility of the teeth in relation to the area of swelling.
Past medical history revealed that the patient was operated upon for retinoblastoma in the right and left eye, at the age of three months and three years respectively, followed by external beam radiotherapy for the left eye with Cobalt 60 using the Tele-Cobalt set up, delivering a total dose of about 40 Gys.
There was no relevant family history and no history of any deleterious habits. On examination, there were no signs of any systemic disease. Examination of the face revealed empty eye sockets and mucous discharge from the left nostril. A single left sub-mandibular lymph node was palpable, 1.5 centimeters in diameter, non-tender, soft and freely mobile.
Intra-oral examination revealed adequate mouth opening with normal appearing buccal mucosa and tongue. In the left maxillary posterior quadrant, there was a well-defined, localized swelling on the palate, roughly oval in shape, extending antero-posteriorly from the rugae area to the posterior aspect of the hard palate, measuring about seven centimeters. Medio-laterally, the swelling extended from the marginal gingiva in relation to 23 to 28 beyond the mid-palate, measuring about five centimeters. The surface was smooth, with no discharge. There was a single ulcer in the anterior portion of the swelling, measuring about 0.5 centimeters, with a linear depression in the posterior aspect [Figure 1]. On palpation, the swelling was non tender and soft to firm in consistency. There was no discharge on provocation. The teeth related to the area of swelling were of grade 2 mobility and showed no displacement.
Based on the history and clinical findings, a provisional diagnosis of carcinoma of left maxillary antrum was established and the differential diagnoses considered were odontogenic tumar adenoid cystic carcinoma and carcinoma of the alveolus.
Following this, radiographic investigations were performed. The intra-oral peri-apical radiograph revealed a diffuse radiolucency circumscribing the root and resorption at apices of 27 and 28. The orthopantomograph revealed an ill- defined radiolucency from the region of 23 to 28 involving the left maxillary sinus [Figure 2]. Paranasal sinus view revealed haziness involving the left antrum [Figure 3]. A CT scan of the paranasal sinus showed a soft tissue mass in the left nasal cavity, measuring 5.34 cms x 4 cms, causing pressure effect over the surrounding structures and pushing the left lateral nasal wall and nasal septum to the right, obliterating the maxillary sinus. Superiorly, the mass lesion extended into the ethmoid sinus and inferiorly eroded the hard palate [Figure 4],[Figure 5].
Following complete hemogram, which was normal, an incisional biopsy was performed, which revealed normal mucosal lining with underlined stroma showing well demarcated tumor, composed of spindle cells arranged in short and long fascicles, having tapering, hyperchromatic nuclei with moderate amount of eosinophilic cytoplasm amidst fibrous stroma and significant mitotic figures. [Figure 6] and [Figure 7]. The features were suggestive of spindle cell sarcoma. Immunohistochemistry was positive for S-100 protein [Figure 8], smooth muscle actin (SMA) and epithelial membrane antigen (EMA) and negative for cytokeratin (CK), desmin and homatropine methyl bromide (HMB-45). The findings were consistent with malignant schwannoma and the patient was kept for further follow-up for treatment.
After a three-day investigatory procedure, the lesion revealed a rapid advancement in size [Figure 9]. We referred the patient to an Oncology centre for further management, where left hemimaxillectomy was performed.
The excised specimen was further subjected to histopathologic examination, which revealed tumor cells with ill-defined margins, extending till the overlying mucosa [Figure 10]. Tumor cells were spindle shaped showing marked pleomorphism and were arranged in the form of long interlacing fascicles [Figure 11]. Giant cells with extensive hyalinization of the stroma were also evident [Figure 12]. Atypical mitosis was observed with no areas of hemorrhage or necrosis [Figure 13]. The histological features were suggestive of spindle cell sarcoma. On subjecting the sections to immuno-histochemistry, the neoplastic spindle cells were seen to be diffusely SMA positive [Figure 14], focally Desmin positive [Figure 15], and negative for CK, EMA, CD34, Myo D1 and S-100.
Hence, a final diagnosis of radiation induced high grade undifferentiated spindle cell sarcoma of the left maxilla was established.
RIS is a well-documented long-term complication of radiotherapy, with an incidence ranging from 0.03% to 0.80%.  Spontaneous development of malignancies in the form of sarcomas is related to the tumorigenic effects of prior radiation therapy in doses ranging from 16 to 112 Gys, and the risk increases further with a total dose of 55 Gy or above. ,,,
In 1948, Cahan et al. described the criteria used for diagnosis of RIS in irradiated bone, which was modified by Arlen et al. in 1971 as follows: (1) history of radiation therapy (2) the development of neoplasm within the field of the radio-therapeutic beam (3) a relatively long period of latency of at least five years and (4) histological proof of a sarcoma. 
In the present subject, who was treated with radiotherapy for retinoblastoma at the age of three years, there was histological evidence of occurrence of spindle cell sarcoma following radiotherapy in the head and neck region after a span of 21 uneventful years. Immunohistochemistry of the biopsy specimen obtained from the lesion was found to be positive for S-100, SMA and EMA, which was most consistent with malignant schwannoma. Based on these findings, the differential diagnosis considered were sarcomatoid carcinoma and malignant spindle cell myoepithelioma but negativity for CK, made these possibilities unlikely. Osteosarcoma was also considered, but was ruled out as no osteoid was evident in the histological section.
However, after the hemimaxillectomy was performed and the excised specimen subjected to immuno-histochemistry, it was seen to be diffusely positive for SMA and focally positive for desmin. Hence, a final diagnosis of radiation induced high grade undifferentiated spindle cell sarcoma of the left maxilla was considered most appropriate.
Documentations reveal that retinoblastoma patients are genetically susceptible for the development of second primary tumors because of an inherited aberrant RB1 gene in all their somatic cells. The risk may be further increased by radiotherapy, through mechanisms which are yet to be determined. 
Patients with bilateral retinoblastoma are carriers of a germline mutation of the RB1 gene and are classified as hereditary (30%-40%). Unilateral patients without a family history (60%-70%) are classified as having non- hereditary disease, where retinoblastoma is presumably caused by somatic mutations of the RB1 gene. Unlike survivors of non-hereditary retinoblastoma, survivors of hereditary retinoblastoma have an elevated risk of developing second malignancies. The presented case had bilateral occurrence of retinoblastoma (hereditary) which places him at high risk of second malignancies. Literature also mentions that the increased risk of second malignancies among hereditary retinoblastoma patients derives mainly from excess risks of soft tissue sarcoma, osteosarcoma, and melanoma. 
Although the incidence of RIS is rare, its biological behavior is more aggressive than spontaneous tumors. Prognosis is also hampered due to limitations in further use of radiation to treat these lesions and their relative insensitivity to chemotherapy. Hence, surgery provides the only chance of cure. 
The reported case demonstrates that the oral diagnosticians as well as pathologists dealing with such patients should be aware of RIS as a long-term complication following radiation treatment of head and neck malignancies. Hence, it is not unreasonable to maintain lifetime follow up of patients previously treated with radiotherapy for head and neck malignancies, to ensure an early diagnosis and treatment.
We would like to place on record our gratitude to Dr. Siddique and Dr. Dayanand, Professors-Department of General Pathology, Bangalore Medical College and Research Institute, Bangalore.
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