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(DarierJDermatofibromes progressifs et recidivants ou fibrosarcomes de la peuAnn Dermatol Syphiligr (Paris)19245542562)
DarierJDermatofibromes progressifs et recidivants ou fibrosarcomes de la peuAnn Dermatol Syphiligr (Paris)19245542562DarierJDermatofibromes progressifs et recidivants ou fibrosarcomes de la peuAnn Dermatol Syphiligr (Paris)19245542562, DarierJDermatofibromes progressifs et recidivants ou fibrosarcomes de la peuAnn Dermatol Syphiligr (Paris)19245542562
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ArnaudEJPerraultMRevolMServantJMBanzetPSurgical treatment of dermatofibrosarcoma protuberansPlast Reconstr Surg199710088489510.1097/00006534-199709001-000099290656ArnaudEJPerraultMRevolMServantJMBanzetPSurgical treatment of dermatofibrosarcoma protuberansPlast Reconstr Surg199710088489510.1097/00006534-199709001-000099290656, ArnaudEJPerraultMRevolMServantJMBanzetPSurgical treatment of dermatofibrosarcoma protuberansPlast Reconstr Surg199710088489510.1097/00006534-199709001-000099290656
N. Lindner, M. Scarborough, G. Powell, S. Spanier, W. Enneking (1999)
Revision surgery in dermatofibrosarcoma protuberans of the trunk and extremities.European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 25 4
(LemmDMuggeLOMentzelTHoffkenKCurrent treatment options in dermatofibrosarcoma protuberansJ Cancer Res Clin Oncol200913565366510.1007/s00432-009-0550-319205737)
LemmDMuggeLOMentzelTHoffkenKCurrent treatment options in dermatofibrosarcoma protuberansJ Cancer Res Clin Oncol200913565366510.1007/s00432-009-0550-319205737LemmDMuggeLOMentzelTHoffkenKCurrent treatment options in dermatofibrosarcoma protuberansJ Cancer Res Clin Oncol200913565366510.1007/s00432-009-0550-319205737, LemmDMuggeLOMentzelTHoffkenKCurrent treatment options in dermatofibrosarcoma protuberansJ Cancer Res Clin Oncol200913565366510.1007/s00432-009-0550-319205737
DFSP is a locally invasive, slow-growing tumor of the subcutaneous tissue that rarely metastasizes but recurs frequently after surgical excision. We report herein a case of highly recurrent, locally invasive DFSP that failed both postoperative radiation therapy and complete trial of Imatinib, but was successfully treated with Sorafenib, which showed unprecedented response. Background Case report Dermatofibrosarcoma Protuberans (DFSP) is a locally A 36 year-old gentleman presented with a left shoulder invasive and slow-growing tumor of the subcutaneous skin lesion that was initially totally excised. Histopath- tissue. It rarely metastasizes. It was first described in ology reported Dermatofibrosarcoma Protuberans (DFSP). 1924 as a progressive and recurrent dermatofibroma [1]. He relapsed sometime after this initial resection and DFSP has an annual incidence of only 0.8 cases per mil- underwent a second surgery followed by several other lion and presents typically at mid-adult life with a slight relapses and re-resections and 2 courses of radiation ther- male predominance [2]. The trunk and proximal extrem- apy and ended up having multifocal disease sites on the ities are the most frequent locations of the disease, but it upper torso, the shoulder and neck. Plastic surgeons can occur at any other site. exhausted all available skin that could be spared for flaps DFSPs rarely progress to a high-grade fibrosarcoma- and reconstruction. After the third relapse and the first tous component [3]. One to 4% of patients will develop round of radiotherapy, he received Imatinib at 400 mg distant metastasis, typically many years after the devel- daily with a positive response lasting for about 2 years. opment of the initial lesion [4]. Upon progression, he was offered Imatinib 800 mg daily According to the NCCN Clinical Practice Guidelines in with non negligible side effects and no response. Oncology, The gold standards treatment is complete surgi- All pathology readings of repeated excisions were cal excision with appropriate reconstruction [5]. Imatinib reported as DFSP except for one time, where the pres- is approved for treatment of advanced disease [6-17]. ence of cellular pleomorphism and the lack of CD 34 ex- When resection is limited or incomplete, or margins are pression raised the possibility of transformation into a positive recurrence rate is high [18-20]. In these cases, adju- fibrosarcoma. Margins following his third resection were vant radiation therapy is recommended as well as Imatinib always positive. based treatment or enrollment in a clinical trial [5]. There was no FISH analysis or RT-PCR or molecular We report hereafter a case of highly recurrent, locally studies ordered to detect the presence of the typical invasive DFSP that failed both postoperative radiation chromosomal translocation t(17;22)(q21;q13) in the tumor therapy and treatment with Imatinib at 400 mg initially of this patient, resulting in the chimeric gene COL1A1- that was then increased to 800 mg. The patient received PDGFB. Sorafenib off label and showed an unprecedented re- The patient ended up with left upper extremity ampu- sponse for his disease. tation at the level of the shoulder and was referred to us. He presented with massive and bulky soft tissue le- sions on his upper torso and in the neck. A contrast en- * Correspondence: kamars@idm.net.lb Division of Hematology & Oncology, Clemenceau Medical Center, City hanced CT scan also revealed large mediastinal masses Center Building, Suite 3 A, Avenue Nouvelle, P.O. Box 1076, Beirut, Jounieh, and post obstructive pneumopathy on the left. Lebanon Full list of author information is available at the end of the article © 2013 Kamar et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Kamar et al. Clinical Sarcoma Research 2013, 3:5 Page 2 of 5 http://www.clinicalsarcomaresearch.com/content/3/1/5 He was offered to start on Sorafenib as it was made The expression of CD34 is almost a consistent finding available for us on compassionate use. A dramatic re- and it is extremely useful in differentiation of DFSP from sponse was seen after only few days of treatment (Figures 1 benign fibrous histiocytoma [32], dermatofibroma and and 2). The patient received Sorafenib 800 mg daily for 5 other soft tissue tumors [33-35]. The sensitivity of CD34 months without recurrence or progression of the tumor. staining in DFSP ranges from 84 to 100% [30]. There was no significant side effect reported beside mod- Cryptogenic abnormalities are also distinguishable char- erate fatigue, and dehiscence of prior surgical wounds. acteristics of DFSP since more than 90% of cases have However, he suffered from recurrent pulmonary infections supernumerary ring chromosomes or a unique translo- despite decompression of his left main bronchus since cation involving chromosomes 17 and 22 as in t(17;22) attaining a very good partial response, and unfortunately (22;q13) [36-41]. This abnormality results in a constitutive passed away after an episode of septic shock. He remained stimulation of the platelet-derived growth factor recep- progression free during the whole treatment time. Ther- tor (PDGFR) with subsequent enhancement of the tumor apy was discontinued only one week prior to his death. cell growth [6,28]. Furthermore, among all the family of PDGF receptors, this translocation is responsible for the Discussion activation of PDGFR-beta [42]. DFSP accounts for 2 to 6% of all soft tissue sarcomas Distant metastasis is rarely observed, with a rate of [21,22]. It is the most frequent skin sarcoma. 4-6%, predominantly to the lungs [20,30]. The tumor involves most frequently the trunk (42-72%), DFSP can transform, especially in the recurring forms, the proximal extremities (16%-30%), and the head and into fibrosarcomatous DFSP (FS-DFSP), a tumor with neck (10-16%) especially the scalp [23-28]. higher invasion and malignancy potential [3,4,28,43]. It The initial presentation of DFSP is a skin lesion de- usually requires a more intensive treatment approach. scribed as a single, raised, red to bluish, firm cutaneous The optimal and the mainstay treatment of DFSP, re- nodule or plaque with surrounding discoloration [29]. gardless of its location, is wide and deep excision with The lesion is painless and indurated, but is extremely in- adequate tumor-free margins. The proper excision with filtrative and has a locally destructive growth that can in- clean margins is directly related to the risk of recurrence vade the underlying structure such as fascia, muscles or of the disease despite adjuvant therapy [18,19,44,45]. bones [18-20,30]. The tumor is often covered by a brown- The involvement of the deep fascia and muscles requires yellow, red-tinged, sclerodermiform or teleangiectatic and excision of these structures [18,19]. atrophic skin [20]. At the initial stages of the disease, his- The most significant prognostic factor in patients with tory of trauma, burn or surgical scar is often found. DFSP has proved to be the extent of surgical resection. At advanced stages, the tumor can ulcerate, bleed, and The success of the initial surgical excision has a major become painful, as reported in our case. effect on the outcome as well. In fact, if this procedure Near to 90% of DFSP are considered to be tumors of fails and hence, the tumor recurs, it could lead to an un- low-grade malignancy [4]. Histologically, DFSP is iden- controllable local growth, as seen in our case. tified by a pattern of monomorphous proliferation of cy- Due to its infiltrative nature, DFSP is characterized tological bland spindle cells with a visible storiform or by a high recurrence rate varying in the literature from whorled (rushmat-like) architecture [4,23,31]. Other char- 10-80% [18]. The risk of recurrence was 41% when the acteristic features are low mitotic activity and deep, honey- excision margin was less than 2 cm and 24% when it comb infiltration into subcutaneous adipose tissue [30]. was equal to or higher than 2 cm [44]. Figure 1 Radiological response to Sorafenib. Kamar et al. Clinical Sarcoma Research 2013, 3:5 Page 3 of 5 http://www.clinicalsarcomaresearch.com/content/3/1/5 Figure 2 Clinical improvement and dramatic shrinking of the tumor. DFSP is considered as one of the radiosensitive tu- remarkable. The tumor almost totally regressed and the pa- mors. Earlier studies suggested that additional postoper- tient improved clinically. This case suggests that Sorafenib ative RT reduces the risk of local recurrence in patients could be an important targeted therapy for DFSP especially with questionable or positive surgical margins [46,47]. in case of recurrence or metastasis. When complete surgical resection is unachievable, RT is indicated [46,48]. RT can reduce the morbidity or func- Conclusion tional impairment associated with extensive resection. Invasive DSFP could be uncontrollable and challenging to As seen in the present case, locally recurrent DFSP cure. We present a case of recurrent and infiltrative DSFP can be devastating. Salvage by further resection increases that failed all conventional therapeutic options. Sorafenib the risk of functional deficits and metastatic disease. was administered as final resort with impressive results. Since the recent identification of the significance of This is to our knowledge the only reported case of PDGFR activation in the DFSP pathogenesis, the effective- DFSP treated with Sorafenib after failure of Imatinib. ness of targeted chemotherapy by inhibition of the PDGFR Sorafenib could represent a therapeutic alternative in protein-tyrosine kinase has been evaluated. Imatinib, a such cases of DFSP. small adenosine triphosphate analog is a selective PDGFR tyrosine kinase-inhibitor. It was approved for the treat- Consent ment of DFSP at a dose of 800 mg daily. Such dose is eas- Written informed consent was obtained from the pa- ily reached orally, with non negligible side effects. Some tient for publication of this report and any accompanying clinical reports showed Imatinib induced regression in pa- images. tients with recurrent or metastatic DFSP [6-17]. Abbreviations However, response was not consistent in all cases as DFSP: Dermatofibrosarcoma protuberans; NCCN: National comprehensive described in our patient. cancer network; FISH: Fluorescence in situ hybridization; PDGFR: Platelet- derived growth factor receptor. To date, no other targeted therapy for DFSP has been reported. Competing interest We report the first case of recurrent and extensive The authors declare that they have no competing interests. DFSP successfully treated with Sorafenib after failure of Authors’ contributions postoperative radiation therapy and refractory to treat- FGK established the conception, the design, and the interpretation of data. ment with 800 mg of Imatinib. After finalizing the draft, he approved of the version to be published. VFK Sorafenib is a small molecule B-raf and vascular endo- has made substantial contributions to acquisition, analysis, and interpretation of data. He also was involved in drafting the manuscript and revising it thelial growth factor (VEGF) receptor inhibitor. It has critically for important intellectual content. ANS contributed in data analysis shown great value in the treatment of angiosarcomas and interpretation, and was involved in revising the critical aspects of the [49] Maki et al., and some other specific sarcoma sub- manuscript. All authors read and approved the final manuscript. types (e.g. peripheral-nerve sheath tumors (MPNST) with Funding loss of NF1 and activation of the ras-raf signaling path- No external funding, apart from the support of the authors' institution, was way) [50-52]. available for this study. Since it has been reported to have an important role Author details in the treatment of some sarcomas, we elected Sorafenib 1 Division of Hematology & Oncology, Clemenceau Medical Center, City as a salvage option for our patient. The response was Center Building, Suite 3 A, Avenue Nouvelle, P.O. Box 1076, Beirut, Jounieh, Kamar et al. Clinical Sarcoma Research 2013, 3:5 Page 4 of 5 http://www.clinicalsarcomaresearch.com/content/3/1/5 Lebanon. Department of Medicine, University at Buffalo, Buffalo, NY, USA. 25. Barnes L, Coleman JA Jr, Johnson JT: Dermatofibrosarcoma protuberans of American University of Beirut Medical Center, Beirut, Lebanon. the head and neck. 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J Biol Chem 1995, 270:28834–28838. doi:10.1186/2045-3329-3-5 Cite this article as: Kamar et al.: Dermatofibrosarcoma protuberans (DFSP) successfully treated with sorafenib: case report. Clinical Sarcoma Research 2013 3:5. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit
Clinical Sarcoma Research – Springer Journals
Published: Apr 4, 2013
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