Dermatofibrosarcoma protuberans: Epidemiology, pathogenesis, clinical presentation, diagnosis, and staging
- 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. Recurrence potential is directly related to the extent of resection. (See "Dermatofibrosarcoma protuberans: Treatment", section on 'Importance of resection margins'.)
This topic review will focus on the epidemiology, molecular pathogenesis, histology, clinical presentation, diagnosis, and staging of DFSP. Treatment of DFSP and issues specific to DFSP arising in the head and neck region are discussed in detail elsewhere. (See "Dermatofibrosarcoma protuberans: Treatment" and "Head and neck sarcomas", section on 'Desmoids and dermatofibrosarcoma protuberans'.)
Dermatofibrosarcoma protuberans (DFSP) is a relatively rare tumor. Estimates of the overall incidence of DFSP in the United States are 0.8 to 4.5 cases per million persons per year [2-4]. In the United States, DFSP accounts for between 1 and 6 percent of all soft tissue sarcomas [5,6] and 18 percent of all cutaneous soft tissue sarcomas . In a series of 12,114 cutaneous soft tissue sarcomas derived from the Surveillance, Epidemiology and End Results (SEER) tumor registry from 1992 through 2004, DFSP was second only to Kaposi sarcoma, which accounted for 71 percent of cases .
The Bednar or pigmented variant (distinguished by the dispersal of melanin-containing cells in an otherwise typical DFSP) is even less common. It represents fewer than 5 percent of all DFSP cases and is more common in black persons [4,7-10]. The fibrosarcomatous variant of DFSP (DFSP-FS) accounts for approximately 5 to 15 percent of DFSPs [11,12].
DFSP most often arises in adults in their thirties [1,4,13-15], but it has been described in all age groups including children and in the elderly; rarely it presents congenitally [1,4,8,14,16-18]. In one large series, children accounted for 6 percent of all cases of DFSP . The so-called giant cell fibroblastoma is considered to be the juvenile form of DFSP, given its similar morphology, identical chromosomal translocation, and CD34 positivity [20-22]. (See 'Molecular diagnostics' below and 'Immunohistochemistry' below.)
- 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.
- Gloster HM Jr. Dermatofibrosarcoma protuberans. J Am Acad Dermatol 1996; 35:355.
- Rouhani P, Fletcher CD, Devesa SS, Toro JR. Cutaneous soft tissue sarcoma incidence patterns in the U.S. : an analysis of 12,114 cases. Cancer 2008; 113:616.
- 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.
- Kransdorf MJ. Malignant soft-tissue tumors in a large referral population: distribution of diagnoses by age, sex, and location. AJR Am J Roentgenol 1995; 164:129.
- 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.
- Yagi Y, Ueda K, Maruyama S, Noborio R. Bednar tumor: a report of two cases. J Dermatol 2004; 31:484.
- Marcus JR, Few JW, Senger C, Reynolds M. Dermatofibrosarcoma protuberans and the Bednar tumor: treatment in the pediatric population. J Pediatr Surg 1998; 33:1811.
- Elgart GW, Hanly A, Busso M, Spencer JM. Bednar tumor (pigmented dermatofibrosarcoma protuberans) occurring in a site of prior immunization: immunochemical findings and therapy. J Am Acad Dermatol 1999; 40:315.
- Dupree WB, Langloss JM, Weiss SW. Pigmented dermatofibrosarcoma protuberans (Bednar tumor). A pathologic, ultrastructural, and immunohistochemical study. Am J Surg Pathol 1985; 9:630.
- 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.
- Stacchiotti S, Pedeutour F, Negri T, et al. Dermatofibrosarcoma protuberans-derived fibrosarcoma: clinical history, biological profile and sensitivity to imatinib. Int J Cancer 2011; 129:1761.
- 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.
- Love WE, Keiler SA, Tamburro JE, et al. Surgical management of congenital dermatofibrosarcoma protuberans. J Am Acad Dermatol 2009; 61:1014.
- Chuang TY, Su WP, Muller SA. Incidence of cutaneous T cell lymphoma and other rare skin cancers in a defined population. J Am Acad Dermatol 1990; 23:254.
- Thornton SL, Reid J, Papay FA, Vidimos AT. Childhood dermatofibrosarcoma protuberans: role of preoperative imaging. J Am Acad Dermatol 2005; 53:76.
- Pappo AS, Rao BN, Cain A, et al. Dermatofibrosarcoma protuberans: the pediatric experience at St. Jude Children's Research Hospital. Pediatr Hematol Oncol 1997; 14:563.
- Weinstein JM, Drolet BA, Esterly NB, et al. Congenital dermatofibrosarcoma protuberans: variability in presentation. Arch Dermatol 2003; 139:207.
- McKee PH, Fletcher CD. Dermatofibrosarcoma protuberans presenting in infancy and childhood. J Cutan Pathol 1991; 18:241.
- Shmookler BM, Enzinger FM, Weiss SW. Giant cell fibroblastoma. A juvenile form of dermatofibrosarcoma protuberans. Cancer 1989; 64:2154.
- Macarenco RS, Zamolyi R, Franco MF, et al. Genomic gains of COL1A1-PDFGB occur in the histologic evolution of giant cell fibroblastoma into dermatofibrosarcoma protuberans. Genes Chromosomes Cancer 2008; 47:260.
- Diwan AH, Skelton HG 3rd, Horenstein MG, et al. Dermatofibrosarcoma protuberans and giant cell fibroblastoma exhibit CD99 positivity. J Cutan Pathol 2008; 35:647.
- Connelly JH, Evans HL. Dermatofibrosarcoma protuberans. A clinicopathologic review with emphasis on fibrosarcomatous areas. Am J Surg Pathol 1992; 16:921.
- 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.
- Rutgers EJ, Kroon BB, Albus-Lutter CE, Gortzak E. Dermatofibrosarcoma protuberans: treatment and prognosis. Eur J Surg Oncol 1992; 18:241.
- 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.
- 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.
- Sirvent N, Maire G, Pedeutour F. Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosomes Cancer 2003; 37:1.
- Nishio J, Iwasaki H, Ishiguro M, et al. Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: a fluorescence in situ hybridization and comparative genomic hybridization analysis. Genes Chromosomes Cancer 2001; 30:305.
- Simon MP, Pedeutour F, Sirvent N, et al. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nat Genet 1997; 15:95.
- Naeem R, Lux ML, Huang SF, et al. Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22. Am J Pathol 1995; 147:1553.
- Salgado R, Llombart B, M Pujol R, et al. Molecular diagnosis of dermatofibrosarcoma protuberans: a comparison between reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization methodologies. Genes Chromosomes Cancer 2011; 50:510.
- 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.
- Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. Dermatofibrosarcoma protuberans and giant cell fibroblastoma. Cancer Genet Cytogenet 2003; 140:1.
- Sjöblom T, Shimizu A, O'Brien KP, et al. Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Res 2001; 61:5778.
- McArthur GA. Dermatofibrosarcoma protuberans: a surgical disease with a molecular savior. Curr Opin Oncol 2006; 18:341.
- 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.
- Patel KU, Szabo SS, Hernandez VS, et al. Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays. Hum Pathol 2008; 39:184.
- Shimizu A, O'Brien KP, Sjöblom T, et al. The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res 1999; 59:3719.
- Llombart B, Sanmartín O, López-Guerrero JA, et al. Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1-PDGFB ) study with therapeutic implications. Histopathology 2009; 54:860.
- Bianchini L, Maire G, Guillot B, et al. Complex t(5;8) involving the CSPG2 and PTK2B genes in a case of dermatofibrosarcoma protuberans without the COL1A1-PDGFB fusion. Virchows Arch 2008; 452:689.
- Gisselsson D, Höglund M, O'Brien KP, et al. A case of dermatofibrosarcoma protuberans with a ring chromosome 5 and a rearranged chromosome 22 containing amplified COL1A1 and PDGFB sequences. Cancer Lett 1998; 133:129.
- Sonobe H, Furihata M, Iwata J, et al. Dermatofibrosarcoma protuberans harboring t(9;22)(q32;q12.2). Cancer Genet Cytogenet 1999; 110:14.
- Nakamura I, Kariya Y, Okada E, et al. A Novel Chromosomal Translocation Associated With COL1A2-PDGFB Gene Fusion in Dermatofibrosarcoma Protuberans: PDGF Expression as a New Diagnostic Tool. JAMA Dermatol 2015; 151:1330.
- Szollosi Z, Scholtz B, Egervari K, Nemes Z. Transformed dermatofibrosarcoma protuberans: real time polymerase chain reaction detection of COL1A1-PDGFB fusion transcripts in sarcomatous areas. J Clin Pathol 2007; 60:190.
- 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.
- Ha SY, Lee SE, Kwon MJ, et al. PDGFB rearrangement in dermatofibrosarcoma protuberans: correlation with clinicopathologic characteristics and clinical implications. Hum Pathol 2013; 44:1300.
- Takahira T, Oda Y, Tamiya S, et al. Microsatellite instability and p53 mutation associated with tumor progression in dermatofibrosarcoma protuberans. Hum Pathol 2004; 35:240.
- Hisaoka M, Okamoto S, Morimitsu Y, et al. Dermatofibrosarcoma protuberans with fibrosarcomatous areas. Molecular abnormalities of the p53 pathway in fibrosarcomatous transformation of dermatofibrosarcoma protuberans. Virchows Arch 1998; 433:323.
- Sasaki M, Ishida T, Horiuchi H, MacHinami R. Dermatofibrosarcoma protuberans: an analysis of proliferative activity, DNA flow cytometry and p53 overexpression with emphasis on its progression. Pathol Int 1999; 49:799.
- Enzinger FM, Weiss SW. Fibrohistiocytic tumors of intermediate malignancy. In: Soft Tissue Tumors, Stamatis G (Ed), Mosby, St. Louis 1988. p.252.
- Tanaka A, Hatoko M, Tada H, et al. Dermatofibrosarcoma protuberans arising from a burn scar of the axilla. Ann Plast Surg 2004; 52:423.
- Green JJ, Heymann WR. Dermatofibrosarcoma protuberans occurring in a smallpox vaccination scar. J Am Acad Dermatol 2003; 48:S54.
- Baker PA, O'Dowd GJ, Khan IU. Dermatofibrosarcoma protuberans arising in a decorative tattoo. Sarcoma 2005; 9:37.
- Hirano SA, Torosky CM. Dermatofibrosarcoma protuberans arising at a Rho(D) immune globulin injection site. Cutis 2012; 90:233.
- Bague S, Folpe AL. Dermatofibrosarcoma protuberans presenting as a subcutaneous mass: a clinicopathological study of 15 cases with exclusive or near-exclusive subcutaneous involvement. Am J Dermatopathol 2008; 30:327.
- Lin JY, Sheen-Chen SM, Hsu W, et al. Dermatofibrosarcoma protuberans of the breast. Tumori 2008; 94:861.
- Lee SJ, Mahoney MC, Shaughnessy E. Dermatofibrosarcoma protuberans of the breast: imaging features and review of the literature. AJR Am J Roentgenol 2009; 193:W64.
- 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.
- Parlette LE, Smith CK, Germain LM, et al. Accelerated growth of dermatofibrosarcoma protuberans during pregnancy. J Am Acad Dermatol 1999; 41:778.
- Har-Shai Y, Govrin-Yehudain J, Ullmann Y, et al. Dermatofibrosarcoma protuberans appearing during pregnancy. Ann Plast Surg 1993; 31:91.
- Mavili ME, Gursu KG, Gokoz A. Dermatofibrosarcoma with lymph node involvement. Ann Plast Surg 1994; 32:438.
- Lemm D, Mügge LO, Mentzel T, Höffken K. Current treatment options in dermatofibrosarcoma protuberans. J Cancer Res Clin Oncol 2009; 135:653.
- Bernard J, Poulalhon N, Argenziano G, et al. Dermoscopy of dermatofibrosarcoma protuberans: a study of 15 cases. Br J Dermatol 2013; 169:85.
- Domanski HA, Gustafson P. Cytologic features of primary, recurrent, and metastatic dermatofibrosarcoma protuberans. Cancer 2002; 96:351.
- Klijanienko J, Caillaud JM, Lagacé R. Fine-needle aspiration of primary and recurrent dermatofibrosarcoma protuberans. Diagn Cytopathol 2004; 30:261.
- Haycox CL, Odland PB, Olbricht SM, Piepkorn M. Immunohistochemical characterization of dermatofibrosarcoma protuberans with practical applications for diagnosis and treatment. J Am Acad Dermatol 1997; 37:438.
- Reimann JD, Fletcher CD. Myxoid dermatofibrosarcoma protuberans: a rare variant analyzed in a series of 23 cases. Am J Surg Pathol 2007; 31:1371.
- Frierson HF, Cooper PH. Myxoid variant of dermatofibrosarcoma protuberans. Am J Surg Pathol 1983; 7:445.
- Mentzel T, Schärer L, Kazakov DV, Michal M. Myxoid dermatofibrosarcoma protuberans: clinicopathologic, immunohistochemical, and molecular analysis of eight cases. Am J Dermatopathol 2007; 29:443.
- BEDNAR B. Storiform neurofibromas of the skin, pigmented and nonpigmented. Cancer 1957; 10:368.
- 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.
- Stojadinovic A, Karpoff HM, Antonescu CR, et al. Dermatofibrosarcoma protuberans of the head and neck. Ann Surg Oncol 2000; 7:696.
- 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.
- Abenoza P, Lillemoe T. CD34 and factor XIIIa in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans. Am J Dermatopathol 1993; 15:429.
- Kamino H, Reddy VB, Gero M, Greco MA. Dermatomyofibroma. A benign cutaneous, plaque-like proliferation of fibroblasts and myofibroblasts in young adults. J Cutan Pathol 1992; 19:85.
- Zelger B, Sidoroff A, Stanzl U, et al. Deep penetrating dermatofibroma versus dermatofibrosarcoma protuberans. A clinicopathologic comparison. Am J Surg Pathol 1994; 18:677.
- Sato N, Kimura K, Tomita Y. Recurrent dermatofibrosarcoma protuberans with myxoid and fibrosarcomatous changes paralleled by loss of CD34 expression. J Dermatol 1995; 22:665.
- Calikoglu E, Augsburger E, Chavaz P, et al. CD44 and hyaluronate in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans. J Cutan Pathol 2003; 30:185.
- Sellheyer K, Nelson P, Krahl D. Dermatofibrosarcoma protuberans: a tumour of nestin-positive cutaneous mesenchymal stem cells? Br J Dermatol 2009; 161:1317.
- Lisovsky M, Hoang MP, Dresser KA, et al. Apolipoprotein D in CD34-positive and CD34-negative cutaneous neoplasms: a useful marker in differentiating superficial acral fibromyxoma from dermatofibrosarcoma protuberans. Mod Pathol 2008; 21:31.
- Yan X, Takahara M, Xie L, et al. Cathepsin K expression: a useful marker for the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans. Histopathology 2010; 57:486.
- Allan AE, Tsou HC, Harrington A, et al. Clonal origin of dermatofibrosarcoma protuberans. J Invest Dermatol 1993; 100:99.
- Dominguez-Malagón HR, Ordóñez NG, Mackay B. Dermatofibrosarcoma protuberans: ultrastructural and immunocytochemical observations. Ultrastruct Pathol 1995; 19:281.
- Aiba S, Tabata N, Ishii H, et al. Dermatofibrosarcoma protuberans is a unique fibrohistiocytic tumour expressing CD34. Br J Dermatol 1992; 127:79.
- Nickoloff BJ. The human progenitor cell antigen (CD34) is localized on endothelial cells, dermal dendritic cells, and perifollicular cells in formalin-fixed normal skin, and on proliferating endothelial cells and stromal spindle-shaped cells in Kaposi's sarcoma. Arch Dermatol 1991; 127:523.
- Kerob D, Pedeutour F, Leboeuf C, et al. Value of cytogenetic analysis in the treatment of dermatofibrosarcoma protuberans. J Clin Oncol 2008; 26:1757.
- Italiano A, Di Mauro I, Rapp J, et al. Clinical effect of molecular methods in sarcoma diagnosis (GENSARC): a prospective, multicentre, observational study. Lancet Oncol 2016; 17:532.
- Young CR 3rd, Albertini MJ. Atrophic dermatofibrosarcoma protuberans: case report, review, and proposed molecular mechanisms. J Am Acad Dermatol 2003; 49:761.
- Fujimoto M, Kikuchi K, Okochi H, Furue M. Atrophic dermatofibrosarcoma protuberans: a case report and review of the literature. Dermatology 1998; 196:422.
- Enneking WF, Spanier SS, Goodman MA. Current concepts review. The surgical staging of musculoskeletal sarcoma. J Bone Joint Surg Am 1980; 62:1027.
- AJCC (American Joint Committee on Cancer). Cancer Staging Manual, 7th edition, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.291.
- Yoon SS, Maki RG, Asare EA, et al.. Soft Tissue Sarcoma of the Trunk and Extremities. In: AJCC Cancer Staging Manual, 8th, Amin. MB. (Ed), AJCC, Chicago 2017. p.507.
- O'Sullivan B, Maki R, Agulnik M, et al.. Soft Tissue Sarcoma of the Head and Neck. In: AJCC Cancer Staging Manual, 8th, Amin MB. (Ed), AJCC, Chicago 2017. p.504.
- Ugurel S, Kortmann RD, Mohr P, et al. Short German guidelines: dermatofibrosarcoma protuberans. J Dtsch Dermatol Ges 2008; 6 Suppl 1:S17.
- Torreggiani WC, Al-Ismail K, Munk PL, et al. Dermatofibrosarcoma protuberans: MR imaging features. AJR Am J Roentgenol 2002; 178:989.
- 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.
- 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.