Dermatofibrosarcoma protuberans: Treatment
- William M Mendenhall, MD
William M Mendenhall, MD
- Department of Radiation Oncology
- University of Florida College of Medicine
- Mark T Scarborough, MD
Mark T Scarborough, MD
- Department of Orthopaedics and Rehabilitation
- University of Florida College of Medicine
- Franklin P Flowers, MD
Franklin P Flowers, MD
- Professor Emeritus
- Division of Dermatology and Cutaneous Surgery
- University of Florida College of Medicine
- Section Editors
- Robert Maki, MD, PhD
Robert Maki, MD, PhD
- Section Editor — Bone and Soft Tissue Tumors
- Professor of Medicine
- Monter Cancer Center
- Hofstra-Northwell School of Medicine
- June K Robinson, MD
June K Robinson, MD
- Section Editor — Nonmelanoma Skin Cancer
- Professor of Clinical Dermatology
- Northwestern University Feinberg School of Medicine
- Raphael E Pollock, MD
Raphael E Pollock, MD
- Editor-in-Chief — General Surgery
- Section Editor — Soft Tissue Sarcoma
- Professor of Surgery
- The Ohio State University
Dermatofibrosarcoma protuberans (DFSP) is an uncommon locally aggressive cutaneous soft tissue sarcoma. Approximately 85 to 90 percent of DFSPs are low grade, while the remainder contain a high-grade sarcomatous component (which is usually a fibrosarcoma, designated DFSP-FS) and are considered to be intermediate-grade sarcomas . Although they rarely metastasize (fewer than 5 percent of cases), all DFSP variants have a propensity to recur locally.
This topic review will focus on treatment of DFSP. The epidemiology, molecular pathogenesis, histology, clinical presentation, diagnosis, and staging of DFSP are discussed elsewhere, as are issues specific to DFSP arising in the head and neck region. (See "Dermatofibrosarcoma protuberans: Epidemiology, pathogenesis, clinical presentation, diagnosis, and staging" and "Head and neck sarcomas", section on 'Desmoids and dermatofibrosarcoma protuberans'.)
The preferred initial treatment for a localized dermatofibrosarcoma protuberans (DFSP) is resection with pathologically negative margins. Tumor size and location dictate the most appropriate surgical procedure. Given that metastases to lymph nodes are extremely rare , there is no role for prophylactic regional node dissection. (See "Dermatofibrosarcoma protuberans: Epidemiology, pathogenesis, clinical presentation, diagnosis, and staging", section on 'Metastatic disease'.)
Importance of resection margins — One of the characteristic features of DFSP is its capacity to invade surrounding tissues in an eccentric fashion to a considerable distance from the central focus of the tumor, with tumor cells invading subcutaneous tissue in the form of irregular tentacle-like projections through the septa and fat lobules. This fact, coupled with the rarity of DFSP and diagnostic delay, often leads to inadequate initial resection. The risk of a local recurrence is as high as 50 percent with simple excision ("conservative" surgical margins), and it is even higher if the margins are positive [1,3-6]. (See "Dermatofibrosarcoma protuberans: Epidemiology, pathogenesis, clinical presentation, diagnosis, and staging", section on 'Histology'.)
The status of the surgical margins is the most important prognostic factor in patients with DFSP:
- Bowne WB, Antonescu CR, Leung DH, et al. Dermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution. Cancer 2000; 88:2711.
- Mavili ME, Gursu KG, Gokoz A. Dermatofibrosarcoma with lymph node involvement. Ann Plast Surg 1994; 32:438.
- Suit H, Spiro I, Mankin HJ, et al. Radiation in management of patients with dermatofibrosarcoma protuberans. J Clin Oncol 1996; 14:2365.
- Rutgers EJ, Kroon BB, Albus-Lutter CE, Gortzak E. Dermatofibrosarcoma protuberans: treatment and prognosis. Eur J Surg Oncol 1992; 18:241.
- Terrier-Lacombe MJ, Guillou L, Maire G, et al. Dermatofibrosarcoma protuberans, giant cell fibroblastoma, and hybrid lesions in children: clinicopathologic comparative analysis of 28 cases with molecular data--a study from the French Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol 2003; 27:27.
- Lemm D, Mügge LO, Mentzel T, Höffken K. Current treatment options in dermatofibrosarcoma protuberans. J Cancer Res Clin Oncol 2009; 135:653.
- Mentzel T, Beham A, Katenkamp D, et al. Fibrosarcomatous ("high-grade") dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance. Am J Surg Pathol 1998; 22:576.
- Khatri VP, Galante JM, Bold RJ, et al. Dermatofibrosarcoma protuberans: reappraisal of wide local excision and impact of inadequate initial treatment. Ann Surg Oncol 2003; 10:1118.
- Arnaud EJ, Perrault M, Revol M, et al. Surgical treatment of dermatofibrosarcoma protuberans. Plast Reconstr Surg 1997; 100:884.
- Serra-Guillén C, Sanmartín O, Llombart B, et al. Correlation between preoperative magnetic resonance imaging and surgical margins with modified Mohs for dermatofibrosarcoma protuberans. Dermatol Surg 2011; 37:1638.
- Kransdorf MJ, Meis-Kindblom JM. Dermatofibrosarcoma protuberans: radiologic appearance. AJR Am J Roentgenol 1994; 163:391.
- Riggs K, McGuigan KL, Morrison WB, et al. Role of magnetic resonance imaging in perioperative assessment of dermatofibrosarcoma protuberans. Dermatol Surg 2009; 35:2036.
- Bergin P, Rezaei S, Lau Q, Coucher J. Dermatofibrosarcoma protuberans, magnetic resonance imaging and pathological correlation. Australas Radiol 2007; 51 Spec No.:B64.
- Thornton SL, Reid J, Papay FA, Vidimos AT. Childhood dermatofibrosarcoma protuberans: role of preoperative imaging. J Am Acad Dermatol 2005; 53:76.
- Torreggiani WC, Al-Ismail K, Munk PL, et al. Dermatofibrosarcoma protuberans: MR imaging features. AJR Am J Roentgenol 2002; 178:989.
- Chang CK, Jacobs IA, Salti GI. Outcomes of surgery for dermatofibrosarcoma protuberans. Eur J Surg Oncol 2004; 30:341.
- Fiore M, Miceli R, Mussi C, et al. Dermatofibrosarcoma protuberans treated at a single institution: a surgical disease with a high cure rate. J Clin Oncol 2005; 23:7669.
- Stojadinovic A, Hoos A, Karpoff HM, et al. Soft tissue tumors of the abdominal wall: analysis of disease patterns and treatment. Arch Surg 2001; 136:70.
- Behbahani R, Patenotre P, Capon N, et al. [To a margin reduction in the dermatofibrosarcoma protuberans? Retrospective study of 34 cases]. Ann Chir Plast Esthet 2005; 50:179.
- Gloster HM Jr, Harris KR, Roenigk RK. A comparison between Mohs micrographic surgery and wide surgical excision for the treatment of dermatofibrosarcoma protuberans. J Am Acad Dermatol 1996; 35:82.
- DuBay D, Cimmino V, Lowe L, et al. Low recurrence rate after surgery for dermatofibrosarcoma protuberans: a multidisciplinary approach from a single institution. Cancer 2004; 100:1008.
- Popov P, Böhling T, Asko-Seljavaara S, Tukiainen E. Microscopic margins and results of surgery for dermatofibrosarcoma protuberans. Plast Reconstr Surg 2007; 119:1779.
- Foroozan M, Sei JF, Amini M, et al. Efficacy of Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans: systematic review. Arch Dermatol 2012; 148:1055.
- Monnier D, Vidal C, Martin L, et al. Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002. J Eur Acad Dermatol Venereol 2006; 20:1237.
- Guillén DR, Cockerell CJ. Cutaneous and subcutaneous sarcomas. Clin Dermatol 2001; 19:262.
- Kimmel Z, Ratner D, Kim JY, et al. Peripheral excision margins for dermatofibrosarcoma protuberans: a meta-analysis of spatial data. Ann Surg Oncol 2007; 14:2113.
- Yu W, Tsoukas MM, Chapman SM, Rosen JM. Surgical treatment for dermatofibrosarcoma protuberans: the Dartmouth experience and literature review. Ann Plast Surg 2008; 60:288.
- Fields RC, Hameed M, Qin LX, et al. Dermatofibrosarcoma protuberans (DFSP): predictors of recurrence and the use of systemic therapy. Ann Surg Oncol 2011; 18:328.
- D'Andrea F, Vozza A, Brongo S, et al. Dermatofibrosarcoma protuberans: experience with 14 cases. J Eur Acad Dermatol Venereol 2001; 15:427.
- Saiag P, Grob JJ, Lebbe C, et al. Diagnosis and treatment of dermatofibrosarcoma protuberans. European consensus-based interdisciplinary guideline. Eur J Cancer 2015; 51:2604.
- Farma JM, Ammori JB, Zager JS, et al. Dermatofibrosarcoma protuberans: how wide should we resect? Ann Surg Oncol 2010; 17:2112.
- Meguerditchian AN, Wang J, Lema B, et al. Wide excision or Mohs micrographic surgery for the treatment of primary dermatofibrosarcoma protuberans. Am J Clin Oncol 2010; 33:300.
- Jimenez FJ, Grichnik JM, Buchanan MD, Clark RE. Immunohistochemical margin control applied to Mohs micrographic surgical excision of dermatofibrosarcoma protuberans. J Dermatol Surg Oncol 1994; 20:687.
- Bogucki B, Neuhaus I, Hurst EA. Dermatofibrosarcoma protuberans: a review of the literature. Dermatol Surg 2012; 38:537.
- Paradisi A, Abeni D, Rusciani A, et al. Dermatofibrosarcoma protuberans: wide local excision vs. Mohs micrographic surgery. Cancer Treat Rev 2008; 34:728.
- Llombart B, Serra-Guillén C, Monteagudo C, et al. Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management. Semin Diagn Pathol 2013; 30:13.
- Tan WP, Barlow RJ, Robson A, et al. Dermatofibrosarcoma protuberans: 35 patients treated with Mohs micrographic surgery using paraffin sections. Br J Dermatol 2011; 164:363.
- Llombart B, Monteagudo C, Sanmartín O, et al. Dermatofibrosarcoma protuberans: a clinicopathological, immunohistochemical, genetic (COL1A1-PDGFB), and therapeutic study of low-grade versus high-grade (fibrosarcomatous) tumors. J Am Acad Dermatol 2011; 65:564.
- Snow SN, Gordon EM, Larson PO, et al. Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature. Cancer 2004; 101:28.
- Wacker J, Khan-Durani B, Hartschuh W. Modified Mohs micrographic surgery in the therapy of dermatofibrosarcoma protuberans: analysis of 22 patients. Ann Surg Oncol 2004; 11:438.
- Nouri K, Lodha R, Jimenez G, Robins P. Mohs micrographic surgery for dermatofibrosarcoma protuberans: University of Miami and NYU experience. Dermatol Surg 2002; 28:1060.
- Robinson JK. Dermatofibrosarcoma protuberans resected by Mohs' surgery (chemosurgery). A 5-year prospective study. J Am Acad Dermatol 1985; 12:1093.
- Ratner D, Thomas CO, Johnson TM, et al. Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans. Results of a multiinstitutional series with an analysis of the extent of microscopic spread. J Am Acad Dermatol 1997; 37:600.
- Haycox CL, Odland PB, Olbricht SM, Casey B. Dermatofibrosarcoma protuberans (DFSP): growth characteristics based on tumor modeling and a review of cases treated with Mohs micrographic surgery. Ann Plast Surg 1997; 38:246.
- Nelson RA, Arlette JP. Mohs micrographic surgery and dermatofibrosarcoma protuberans: a multidisciplinary approach in 44 patients. Ann Plast Surg 2008; 60:667.
- Serra-Guillén C, Llombart B, Nagore E, et al. Mohs micrographic surgery in dermatofibrosarcoma protuberans allows tumour clearance with smaller margins and greater preservation of healthy tissue compared with conventional surgery: a study of 74 primary cases. Br J Dermatol 2015; 172:1303.
- Loghdey MS, Varma S, Rajpara SM, et al. Mohs micrographic surgery for dermatofibrosarcoma protuberans (DFSP): a single-centre series of 76 patients treated by frozen-section Mohs micrographic surgery with a review of the literature. J Plast Reconstr Aesthet Surg 2014; 67:1315.
- Ah-Weng A, Marsden JR, Sanders DS, Waters R. Dermatofibrosarcoma protuberans treated by micrographic surgery. Br J Cancer 2002; 87:1386.
- Massey RA, Tok J, Strippoli BA, et al. A comparison of frozen and paraffin sections in dermatofibrosarcoma protuberans. Dermatol Surg 1998; 24:995.
- Matin RN, Acland KM, Williams HC. Is Mohs micrographic surgery more effective than wide local excision for treatment of dermatofibrosarcoma protuberans in reducing risk of local recurrence? A Critically Appraised Topic. Br J Dermatol 2012; 167:6.
- Ballo MT, Zagars GK, Pisters P, Pollack A. The role of radiation therapy in the management of dermatofibrosarcoma protuberans. Int J Radiat Oncol Biol Phys 1998; 40:823.
- Lindner NJ, Scarborough MT, Powell GJ, et al. Revision surgery in dermatofibrosarcoma protuberans of the trunk and extremities. Eur J Surg Oncol 1999; 25:392.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- Sun LM, Wang CJ, Huang CC, et al. Dermatofibrosarcoma protuberans: treatment results of 35 cases. Radiother Oncol 2000; 57:175.
- Haas RL, Keus RB, Loftus BM, et al. The role of radiotherapy in the local management of dermatofibrosarcoma protuberans. Soft Tissue Tumours Working Group. Eur J Cancer 1997; 33:1055.
- Dagan R, Morris CG, Zlotecki RA, et al. Radiotherapy in the treatment of dermatofibrosarcoma protuberans. Am J Clin Oncol 2005; 28:537.
- Parsons JT, Zlotecki RA, Reddy KA, et al. The role of radiotherapy and limb-conserving surgery in the management of soft-tissue sarcomas in adults. Hematol Oncol Clin North Am 2001; 15:377.
- Kreicher KL, Kurlander DE, Gittleman HR, et al. Incidence and Survival of Primary Dermatofibrosarcoma Protuberans in the United States. Dermatol Surg 2016; 42 Suppl 1:S24.
- Goldblum JR, Reith JD, Weiss SW. Sarcomas arising in dermatofibrosarcoma protuberans: a reappraisal of biologic behavior in eighteen cases treated by wide local excision with extended clinical follow up. Am J Surg Pathol 2000; 24:1125.
- Gayner SM, Lewis JE, McCaffrey TV. Effect of resection margins on dermatofibrosarcoma protuberans of the head and neck. Arch Otolaryngol Head Neck Surg 1997; 123:430.
- Connelly JH, Evans HL. Dermatofibrosarcoma protuberans. A clinicopathologic review with emphasis on fibrosarcomatous areas. Am J Surg Pathol 1992; 16:921.
- Abbott JJ, Oliveira AM, Nascimento AG. The prognostic significance of fibrosarcomatous transformation in dermatofibrosarcoma protuberans. Am J Surg Pathol 2006; 30:436.
- Ding J, Hashimoto H, Enjoji M. Dermatofibrosarcoma protuberans with fibrosarcomatous areas. A clinicopathologic study of nine cases and a comparison with allied tumors. Cancer 1989; 64:721.
- Szollosi Z, Nemes Z. Transformed dermatofibrosarcoma protuberans: a clinicopathological study of eight cases. J Clin Pathol 2005; 58:751.
- Cai H, Wang Y, Wu J, Shi Y. Dermatofibrosarcoma protuberans: clinical diagnoses and treatment results of 260 cases in China. J Surg Oncol 2012; 105:142.
- Liang CA, Jambusaria-Pahlajani A, Karia PS, et al. A systematic review of outcome data for dermatofibrosarcoma protuberans with and without fibrosarcomatous change. J Am Acad Dermatol 2014; 71:781.
- Wrotnowski U, Cooper PH, Shmookler BM. Fibrosarcomatous change in dermatofibrosarcoma protuberans. Am J Surg Pathol 1988; 12:287.
- Castle KO, Guadagnolo BA, Tsai CJ, et al. Dermatofibrosarcoma protuberans: long-term outcomes of 53 patients treated with conservative surgery and radiation therapy. Int J Radiat Oncol Biol Phys 2013; 86:585.
- Kabumoto T, Fujiwara H, Kariya N, et al. Skin metastasis of dermatofibrosarcoma protuberans with distinct morphological features, confirmed by COL1A1-PDGFB fusion gene analysis. J Am Acad Dermatol 2009; 61:130.
- Lal P, Sharma R, Mohan H, Sekhon MS. Dermatofibrosarcoma protuberans metastasizing to lymph nodes: a case report and review of literature. J Surg Oncol 1999; 72:178.
- Westermann GW, Buerger H, Kappes U, et al. Dermatofibrosarcoma protuberans with lung metastasis in a patient with progressive systemic sclerosis. South Med J 2002; 95:363.
- Maki RG, Awan RA, Dixon RH, et al. Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans. Int J Cancer 2002; 100:623.
- Kerob D, Pedeutour F, Leboeuf C, et al. Value of cytogenetic analysis in the treatment of dermatofibrosarcoma protuberans. J Clin Oncol 2008; 26:1757.
- McArthur GA, Demetri GD, van Oosterom A, et al. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol 2005; 23:866.
- Mizutani K, Tamada Y, Hara K, et al. Imatinib mesylate inhibits the growth of metastatic lung lesions in a patient with dermatofibrosarcoma protuberans. Br J Dermatol 2004; 151:235.
- Rubin BP, Schuetze SM, Eary JF, et al. Molecular targeting of platelet-derived growth factor B by imatinib mesylate in a patient with metastatic dermatofibrosarcoma protuberans. J Clin Oncol 2002; 20:3586.
- Rutkowski P, Van Glabbeke M, Rankin CJ, et al. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol 2010; 28:1772.
- Labropoulos SV, Fletcher JA, Oliveira AM, et al. Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate. Anticancer Drugs 2005; 16:461.
- Kiuru-Kuhlefelt S, El-Rifai W, Fanburg-Smith J, et al. Concomitant DNA copy number amplification at 17q and 22q in dermatofibrosarcoma protuberans. Cytogenet Cell Genet 2001; 92:192.
- Abbott JJ, Erickson-Johnson M, Wang X, et al. Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans. Mod Pathol 2006; 19:1512.
- Wang J, Morimitsu Y, Okamoto S, et al. COL1A1-PDGFB fusion transcripts in fibrosarcomatous areas of six dermatofibrosarcomas protuberans. J Mol Diagn 2000; 2:47.
- Stacchiotti S, Pantaleo MA, Negri T, et al. Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP). Clin Cancer Res 2016; 22:837.
- Lemm D, Muegge LO, Hoeffken K, et al. Remission with Imatinib mesylate treatment in a patient with initially unresectable dermatofibrosarcoma protuberans--a case report. Oral Maxillofac Surg 2008; 12:209.
- Ugurel S, Mentzel T, Utikal J, et al. Neoadjuvant imatinib in advanced primary or locally recurrent dermatofibrosarcoma protuberans: a multicenter phase II DeCOG trial with long-term follow-up. Clin Cancer Res 2014; 20:499.
- Rutkowski P, Dębiec-Rychter M, Nowecki Z, et al. Treatment of advanced dermatofibrosarcoma protuberans with imatinib mesylate with or without surgical resection. J Eur Acad Dermatol Venereol 2011; 25:264.
- Kérob D, Porcher R, Vérola O, et al. Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: results of a multicenter phase II study on 25 patients. Clin Cancer Res 2010; 16:3288.
- Neoadjuvant imatinib in DFSP, sponsored by the Sarcoma Alliance for Research through Collaboration. http://clinicaltrials.gov/ct2/show/NCT00243191?term=00243191&rank=1 (Accessed on November 01, 2012).
- A short course of neoadjuvant Gleevec (imatinib mesylate) in DFSP (NCT 00176709). http://clinicaltrials.gov/ct2/results?term=00176709 (Accessed on November 01, 2012).
- Kamar FG, Kairouz VF, Sabri AN. Dermatofibrosarcoma protuberans (DFSP) successfully treated with sorafenib: case report. Clin Sarcoma Res 2013; 3:5.
- Ong HS, Ji T, Wang LZ, et al. Dermatofibrosarcoma protuberans on the right neck with superior vena cava syndrome: case report and literature review. Int J Oral Maxillofac Surg 2013; 42:707.
- Ng A, Nishikawa H, Lander A, Grundy R. Chemosensitivity in pediatric dermatofibrosarcoma protuberans. J Pediatr Hematol Oncol 2005; 27:100.
- LOCALIZED DISEASE
- Importance of resection margins
- - Role of diagnostic imaging
- Surgical techniques
- - Wide local excision
- - Mohs micrographic surgery
- - RT following surgical resection
- Posttreatment surveillance
- TREATMENT OF LOCALLY ADVANCED, RECURRENT, AND METASTATIC DISEASE
- Molecularly targeted therapy
- - Imatinib
- Neoadjuvant and adjuvant imatinib
- - Other tyrosine kinase inhibitors
- Conventional chemotherapy
- SUMMARY AND RECOMMENDATIONS
- Treatment of localized disease
- Treatment for locally advanced and metastatic disease