Dermatofibrosarcoma Protuberans (DFSP) is a locally invasive and slow-growing tumor of the subcutaneous tissue. It rarely metastasizes. It was first described in 1924 as a progressive and recurrent dermatofibroma [1]. DFSP has an annual incidence of only 0.8 cases per million and presents typically at mid-adult life with a slight male predominance [2]. The trunk and proximal extremities are the most frequent locations of the disease, but it can occur at any other site. DFSPs rarely progress to a high-grade fibrosarcomatous component [3]. One to 4% of patients will develop distant metastasis, typically many years after the development of the initial lesion [4]. According to the NCCN Clinical Practice Guidelines in Oncology, The gold standards treatment is complete surgical excision with appropriate reconstruction [5]. Imatinib is approved for treatment of advanced disease [6-17]. When resection is limited or incomplete, or margins are positive recurrence rate is high [18-20]. In these cases, adjuvant radiation therapy is recommended as well as Imatinib based treatment or enrollment in a clinical trial [5]. We report hereafter a case of highly recurrent, locally invasive DFSP that failed both postoperative radiation therapy and treatment with Imatinib at 400 mg initially that was then increased to 800 mg. The patient received Sorafenib off label and showed an unprecedented response for his disease.

A 36 year-old gentleman presented with a left shoulder skin lesion that was initially totally excised. Histopathology reported Dermatofibrosarcoma Protuberans (DFSP). He relapsed sometime after this initial resection and underwent a second surgery followed by several other relapses and re-resections and 2 courses of radiation therapy and ended up having multifocal disease sites on the upper torso, the shoulder and neck. Plastic surgeons exhausted all available skin that could be spared for flaps and reconstruction. After the third relapse and the first round of radiotherapy, he received Imatinib at 400 mg daily with a positive response lasting for about 2 years. Upon progression, he was offered Imatinib 800 mg daily with non negligible side effects and no response.

All pathology readings of repeated excisions were reported as DFSP except for one time, where the presence of cellular pleomorphism and the lack of CD 34 expression raised the possibility of transformation into a fibrosarcoma. Margins following his third resection were always positive.

There was no FISH analysis or RT-PCR or molecular studies ordered to detect the presence of the typical chromosomal translocation t(17;22)(q21;q13) in the tumor of this patient, resulting in the chimeric gene COL1A1- PDGFB.

The patient ended up with left upper extremity amputation at the level of the shoulder and was referred to us.

He presented with massive and bulky soft tissue lesions on his upper torso and in the neck. A contrast enhanced CT scan also revealed large mediastinal masses and post obstructive pneumopathy on the left.

He was offered to start on Sorafenib as it was made available for us on compassionate use. A dramatic response was seen after only few days of treatment (Figures 1 and 2). The patient received Sorafenib 800 mg daily for 5 months without recurrence or progression of the tumor. There was no significant side effect reported beside moderate fatigue, and dehiscence of prior surgical wounds. However, he suffered from recurrent pulmonary infections despite decompression of his left main bronchus since attaining a very good partial response, and unfortunately passed away after an episode of septic shock. He remained progression free during the whole treatment time. Therapy was discontinued only one week prior to his death...