eMedicine Specialties > Dermatology > Malignant Neoplasms

Dermatofibrosarcoma Protuberans: Treatment & Medication

Author: Chih-Shan Jason Chen, MD, PhD, Associate Attending, Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York; Director, Dermatologic Surgery and Mohs Micrographic Surgery Unit, MSK Skin Cancer Center at Hauppauge, Long Island; Chief, Dermatologic Surgery, Northport Veterans Affairs Medical Center, Northport, Long Island
Coauthor(s): Daniel Mark Siegel, MD, MS, Director, Procedural Dermatology Fellowship Program, Clinical Professor of Dermatology, Department of Dermatology, State University of New York Downstate
Contributor Information and Disclosures

Updated: Aug 17, 2009

Treatment

Medical Care

Currently, chemotherapy is rarely used in the treatment of dermatofibrosarcoma protuberans (DFSP). Radiation therapy has had a limited role in the past, but, recently, it has been used as an adjunct to surgery. Radiation therapy may be recommended for patients if the margins of resection are positive or for situations in which adequate wide excision alone may result in major cosmetic or functional deficits. The complete radiation therapy dose ranges from 60-70 Gy. Close follow-up care after radiation therapy is warranted because some DFSP tumors may become more aggressive.1,15,23

The development of molecularly targeted therapy holds promise as an additional treatment option. Originally approved for the treatment of chronic myelogenic leukemia, imatinib mesylate has been found to have significant therapeutic value in the treatment of DFSP. Imatinib is a potent and specific inhibitor of several protein-tyrosine kinases, including the PDGF receptors.5
 
On October 19, 2006, the US Food and Drug Administration granted approval for imatinib mesylate (Gleevec) as a single agent for the treatment of DFSP. Imatinib mesylate is indicated for the treatment of adult patients with unresectable, recurrent, and/or metastatic DFSP. The recommended dose is 800 mg/d.18

With limited clinical data to date, a response rate of approximately 65% has been achieved among DFSP patients treated with imatinib. A small subset of DFSP lacking the classic t(17,22) gene aberration seems to have no response to imatinib.1  

For a partial listing of active and recruiting clinical trials, see Further Reading.

Surgical Care

Surgical excision remains the mainstay of treatment for dermatofibrosarcoma protuberans (DFSP). Mohs micrographic surgery has been increasingly accepted as the treatment of choice (see Mohs Micrographic Surgery).13

Because of its infiltrating growth pattern, DFSP commonly extends far beyond the clinical margins; this accounts in part for the high recurrence rate after standard surgical excision. Hence, a wide excision of 3 cm or more of the margins, down to and including the fascia, is recommended for the treatment of DFSP. Despite wide local excisions, an average recurrence rate of 15.7% is still observed among 1201 body cases and 51.8% is observed among 193 head and neck cases, as reported in the literature since 1951. A superior cure rate (an overall average recurrence rate of 1.3% among 463 cases reported) and tissue conservation are seen when Mohs micrographic surgery is used; thus, Mohs micrographic surgery is now considered the treatment of choice, particularly when a lesion is located in the head and neck region.19,24,25,26,27,28,29

Although some Mohs surgeons consider it unnecessary, taking an extra layer of tissue around the surgical defect at the completion of Mohs surgery for permanent pathology section and/or CD34 immunostaining may potentially enhance the cure rate. Alternatively, some have adopted modified Mohs techniques, or so called "slow Mohs," by using rush paraffin sections instead of a fresh tissue technique.27,24,30,31,32

Medication

Although medical therapy is not a first-line treatment for localized dermatofibrosarcoma protuberans (DFSP), the newly approved molecular targeted drug, imatinib mesylate, is an effective oral medication for unresectable, recurrent, and/or metastatic DFSP.

Molecular targeted therapy

Before starting imatinib therapy, cytogenetic studies to confirm PDGFB gene rearrangement may be necessary in predicting the clinical response. Chromosome translocation t(17,22) is detected in more than 90% of DFSP tumors.


Imatinib mesylate (Gleevec)

Inhibitor of receptor tyrosine kinase for PDGF. Inhibits PDGF-B receptor-mediated cellular events, the key pathogenetic pathway in DFSP.

Adult

800 mg/d PO divided bid

Pediatric

Not established

CYP3A4 inhibitors (ketoconazole increases distribution of imatinib); CYP3A4 substrates (simvastatin increases maximum concentration of imatinib by a 2- to 3.5-fold factor); CYP3A4 inducers (phenytoin decreases AUC by approximately one fifth of typical AUC); likely to increase blood levels of drugs that are substrates of CYP2C9, CYP2D6, and CYP3A4/5
Increase dose by at least 50% in patients receiving concomitant CYP3A4 inducers (eg, rifampin, phenytoin)

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Dose must be reduced or interrupted if edema or anemia occurs, transaminase or bilirubin levels become elevated, or grade 3-4 neutropenia or thrombocytopenia develops; pediatric patients commonly experience musculoskeletal pain
Adverse effects include congestive heart failure, increased risk of hypereosinophilic cardiac toxicity, grade 3-4 gastrointestinal and tumor site bleeding, pleural effusion, and gastrointestinal perforation (including fatalities); increased risk of edema, severe congestive heart failure, and left ventricular dysfunction reported in elderly persons (>65 y); fatigue, hypokalemia, and hypophosphatemia reported; monitor CBC counts qwk for first month, q2wk for second month, and periodically thereafter; perform liver function tests at baseline and then monthly or as clinically indicated
Initiation in post-thyroidectomy patients receiving levothyroxine has resulted in elevated levels of thyrotropin and symptoms of hypothyroidism

More on Dermatofibrosarcoma Protuberans

Overview: Dermatofibrosarcoma Protuberans
Differential Diagnoses & Workup: Dermatofibrosarcoma Protuberans
Treatment & Medication: Dermatofibrosarcoma Protuberans
Follow-up: Dermatofibrosarcoma Protuberans
Multimedia: Dermatofibrosarcoma Protuberans
References
Further Reading
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References

  1. Lemm D, Mugge LO, Mentzel T, Hoffken K. Current treatment options in dermatofibrosarcoma protuberans. J Cancer Res Clin Oncol. May 2009;135(5):653-65. [Medline].

  2. Dimitropoulos VA. Dermatofibrosarcoma protuberans. Dermatol Ther. Nov-Dec 2008;21(6):428-32. [Medline].

  3. Gisselsson D, Hoglund M, O'Brien KP, Dumanski JP, Mertens F, Mandahl N. A case of dermatofibrosarcoma protuberans with a ring chromosome 5 and a rearranged chromosome 22 containing amplified COL1A1 and PDGFB sequences. Cancer Lett. Nov 27 1998;133(2):129-34. [Medline].

  4. Kikuchi K, Soma Y, Fujimoto M, et al. Dermatofibrosarcoma protuberans: increased growth response to platelet-derived growth factor BB in cell culture. Biochem Biophys Res Commun. Oct 15 1993;196(1):409-415. [Medline].

  5. McArthur G. Molecularly targeted treatment for dermatofibrosarcoma protuberans. Semin Oncol. Apr 2004;31(2 Suppl 6):30-6. [Medline].

  6. Naeem R, Lux ML, Huang SF, Naber SP, Corson JM, Fletcher JA. Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22. Am J Pathol. Dec 1995;147(6):1553-8. [Medline].

  7. Shimizu A, O'Brien KP, Sjoblom 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. Aug 1 1999;59(15):3719-23. [Medline].

  8. 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. Jan 1997;15(1):95-8. [Medline].

  9. Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. Jun 2007;56(6):968-73. [Medline].

  10. 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. Nov 2006;20(10):1237-42. [Medline].

  11. Abbott JJ, Oliveira AM, Nascimento AG. The prognostic significance of fibrosarcomatous transformation in dermatofibrosarcoma protuberans. Am J Surg Pathol. Apr 2006;30(4):436-43. [Medline].

  12. Rutgers EJ, Kroon BB, Albus-Lutter CE, Gortzak E. Dermatofibrosarcoma protuberans: treatment and prognosis. Eur J Surg Oncol. Jun 1992;18(3):241-8. [Medline].

  13. 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. Jul 1996;35(1):82-7. [Medline].

  14. McLelland J, Chu T. Dermatofibrosarcoma protuberans arising in a BCG vaccination scar. Arch Dermatol. Apr 1988;124(4):496-7. [Medline].

  15. Ugurel S, Kortmann RD, Mohr P, Mentzel T, Garbe C, Breuninger H. Short German guidelines: dermatofibrosarcoma protuberans. J Dtsch Dermatol Ges. May 2008;6 Suppl 1:S17-8. [Medline].

  16. Thornton SL, Reid J, Papay FA, Vidimos AT. Childhood dermatofibrosarcoma protuberans: role of preoperative imaging. J Am Acad Dermatol. Jul 2005;53(1):76-83. [Medline].

  17. Torreggiani WC, Al-Ismail K, Munk PL, Nicolaou S, O'Connell JX, Knowling MA. Dermatofibrosarcoma protuberans: MR imaging features. AJR Am J Roentgenol. Apr 2002;178(4):989-93. [Medline].

  18. McArthur G. Dermatofibrosarcoma protuberans: recent clinical progress. Ann Surg Oncol. Oct 2007;14(10):2876-86. [Medline].

  19. Bowne WB, Antonescu CR, Leung DH, et al. Dermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution. Cancer. Jun 15 2000;88(12):2711-20. [Medline].

  20. Quigley EA, Marghoob AA, Busam KJ, Chen CS. A firm red-brown plaque on the arm. Dermatofibrosarcoma protuberans(DFSP), pigmented variant (Bednar tumor. Arch Dermatol. May 2009;145(5):589-94. [Medline].

  21. Abenoza P, Lillemoe T. CD34 and factor XIIIa in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans. Am J Dermatopathol. Oct 1993;15(5):429-34. [Medline].

  22. Prieto VG, Reed JA, Shea CR. CD34 immunoreactivity distinguishes between scar tissue and residual tumor in re-excisional specimens of dermatofibrosarcoma protuberans. J Cutan Pathol. Aug 1994;21(4):324-9. [Medline].

  23. Dagan R, Morris CG, Zlotecki RA, Scarborough MT, Mendenhall WM. Radiotherapy in the treatment of dermatofibrosarcoma protuberans. Am J Clin Oncol. Dec 2005;28(6):537-9. [Medline].

  24. Hancox JG, Kelley B, Greenway HT Jr. Treatment of dermatofibroma sarcoma protuberans using modified Mohs micrographic surgery: no recurrences and smaller defects. Dermatol Surg. Jun 2008;34(6):780-4. [Medline].

  25. Nelson RA, Arlette JP. Mohs micrographic surgery and dermatofibrosarcoma protuberans: a multidisciplinary approach in 44 patients. Ann Plast Surg. Jun 2008;60(6):667-72. [Medline].

  26. Nouri K, Lodha R, Jimenez G, Robins P. Mohs micrographic surgery for dermatofibrosarcoma protuberans: University of Miami and NYU experience. Dermatol Surg. Nov 2002;28(11):1060-4; discussion 1064. [Medline].

  27. Paradisi A, Abeni D, Rusciani A, et al. Dermatofibrosarcoma protuberans: wide local excision vs. Mohs micrographic surgery. Cancer Treat Rev. Dec 2008;34(8):728-36. [Medline].

  28. 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. Oct 1997;37(4):600-13. [Medline].

  29. Snow SN, Gordon EM, Larson PO, Bagheri MM, Bentz ML, Sable DB. Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature. Cancer. Jul 1 2004;101(1):28-38. [Medline].

  30. Cecchi R, Rapicano V. Micrographic surgery (Tübingen technique) for the treatment of dermatofibrosarcoma protuberans: a single-centre experience. Eur J Dermatol. Nov-Dec 2007;17(6):543-4. [Medline].

  31. Hafner HM, Moehrle M, Eder S, Trilling B, Rocken M, Breuninger H. 3D-Histological evaluation of surgery in dermatofibrosarcoma protuberans and malignant fibrous histiocytoma: differences in growth patterns and outcome. Eur J Surg Oncol. Jun 2008;34(6):680-6. [Medline].

  32. Kimmel Z, Ratner D, Kim JY, Wayne JD, Rademaker AW, Alam M. Peripheral excision margins for dermatofibrosarcoma protuberans: a meta-analysis of spatial data. Ann Surg Oncol. Jul 2007;14(7):2113-20. [Medline].

  33. 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. Sep 1999;49(9):799-806. [Medline].

  34. Brown MD. Recognition and management of unusual cutaneous tumors. Dermatol Clin. Jul 2000;18(3):543-52. [Medline].

  35. Dawes KW, Hanke CW. Dermatofibrosarcoma protuberans treated with Mohs micrographic surgery: cure rates and surgical margins. Dermatol Surg. Jun 1996;22(6):530-4. [Medline].

  36. 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. Oct 20 2005;23(30):7669-75. [Medline].

  37. Gloster HM Jr. Dermatofibrosarcoma protuberans. J Am Acad Dermatol. Sep 1996;35(3 Pt 1):355-74; quiz 375-6. [Medline].

  38. Gutierrez G, Ospina JE, de Baez NE, de Escorcia EK, Gutierrez R. Dermatofibrosarcoma protuberans. Int J Dermatol. Jul-Aug 1984;23(6):396-401. [Medline].

  39. 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. Feb 1 2005;23(4):866-73. [Medline].

  40. Mendenhall WM, Zlotecki RA, Scarborough MT. Dermatofibrosarcoma protuberans. Cancer. Dec 1 2004;101(11):2503-8. [Medline].

  41. Peters CW, Hanke CW, Pasarell HA, Bennett JE. Chemosurgical reports. Dermatofibrosarcoma protuberans of the face. J Dermatol Surg Oncol. Oct 1982;8(10):823-6. [Medline].

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Keywords

dermatofibrosarcoma protuberans, DFSP, sarcomatous tumors resembling keloid, hypertrophic morphea, progressive and recurring dermatofibroma, fibrosarcomatous tumors with attenuated dermal surfaces, fibrosarcoma of the skin

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Contributor Information and Disclosures

Author

Chih-Shan Jason Chen, MD, PhD, Associate Attending, Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York; Director, Dermatologic Surgery and Mohs Micrographic Surgery Unit, MSK Skin Cancer Center at Hauppauge, Long Island; Chief, Dermatologic Surgery, Northport Veterans Affairs Medical Center, Northport, Long Island
Chih-Shan Jason Chen, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Society for Dermatologic Surgery, Association of Professors of Dermatology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Daniel Mark Siegel, MD, MS, Director, Procedural Dermatology Fellowship Program, Clinical Professor of Dermatology, Department of Dermatology, State University of New York Downstate
Daniel Mark Siegel, MD, MS is a member of the following medical societies: American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American College of Physician Executives, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, American Society for MOHS Surgery, and International Society for Dermatologic Surgery
Disclosure: Nothing to disclose.

Medical Editor

Abdul-Ghani Kibbi, MD, Chairman and Professor, Department of Dermatology, American University of Beirut Medical Center, Lebanon
Disclosure: none None None

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

John G Albertini, MD, Consulting Staff, Dermatologic Surgery, The Skin Surgery Center
John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology and American College of Mohs Micrographic Surgery and Cutaneous Oncology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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