KIT expression in postradiation sarcoma

Dear Editor, Postradiation sarcomas (PRS) are rare and critical long-term complications of radiotherapy as they are usually aggressive and hardly curable tumours [1]. The prognosis of PRS is generally thought to be worse than that for primary sarcomas regardless of site of origin [1,2]. PRS diagnostic criteria are: development in a previously irradiated field, histological confirmation of the diagnosis, a latency period of at least 3 years between irradiation and appearance of the tumour, and documentation that the region bearing the tumour was normal prior to administration of radiation [2]. Most frequent histological subtypes of PRS are pleomorphic undifferentiated sarcoma (malignant fibrous histiocytoma), osteosarcoma, fibrosarcoma, malignant peripheral nerve sheath tumour, chondrosarcoma and angiosarcoma [2]. We report the case of a PRS of the thorax in a 69-year-old man who had received radiation therapy for a non-Hodgkin lymphoma of the tonsils at the age of 44 years. He was treated with chemotherapy and radiation therapy, receiving 40 Grays on the Waldeyer ring area and in a mantlet form excluding the mediastinum, and was considered cured from the lymphoma. Twenty-five years later, he presented with dysaesthesia of the right hand. Physical examination revealed a moderately firm mass located between the right pectoralis minor and pectoralis major muscles. There was no palpable axillary lymph node. Computed tomography showed an oval mass measuring 50 · 25 mm with liquid density and weak contrast enhancement, whereas ultrasound examination was in favour of solid tissue. Ultrasound-guided fine needle aspiration cytology (FNAC) was performed and cytological smears featured dense cellular clusters and atypical round and ovoid shaped dispersed pleomorphic cells admixed with an abundant myxoid material (Figure 1). Neither necrosis nor mitoses were observed. The cytological report ruled out haematological disease and stated mesenchymal tumour of uncertain type, malignancy not excluded, and requiring histopathological examination . Surgical excision was performed shortly after. Histologically, the tumour was heterogeneous, showing myxoid and cellular areas composed of highly pleomorphic, often multinucleated spindle cells (Figure 2a). There were around 50 mitoses per 10 high-power fields (·400), and few necrotic areas were observed. Immunostainings with antibodies directed against smooth muscle actin, protein S100, caldesmon, desmin, myogenin and MDM2 were all negative. Few scattered tumour cells expressed CD34. A final diagnosis of high-grade pleomorphic undifferentiated sarcoma was rendered. In accordance with two reports showing c-Kit expression in PRS [3,4], we also detected its presence immunohistochemically (polyclonal rabbit antibody A4502; Dako, Glostrup, Denmark) in numerous neoplastic cells, with moderate intensity (Figure 2b). In these previous studies the authors also sequenced exon 11 of the corresponding gene in tumour cells, given that mutations of this exon are associated with a better response to c-Kit pharmacological inhibitors in gastrointestinal stromal tumours (GISTs) [5], but found no mutations. We performed complete sequencing of the c-Kit gene using DNA extracted from paraffin-embedded neoplastic tissue and no mutations were disclosed. We additionally performed sequencing of the platelet-derived growth factor receptor alpha gene which has been reported to be mutated in a Correspondence: Felipe Andreiuolo, Department of Biopathology, Institut Gustave Roussy, 39, rue Camille Desmoulins 94805 Villejuif, France. Tel. : +33 1 45 654 364; Fax: +33 1 45 655 280; E-mail: felipe.andreiuolo@igr.fr K. -C. Wang, J.-D. Hsu and C. -C. Yao have contributed equally. Figure 1. Fine needle aspiration cytology material shows dense cellular clusters and highly atypical dispersed tumour cells in a myxoid background. Correspondence 279