Using Imatinib as Neoadjuvant Therapy in Dermatofibrosarcoma Protuberans: Potential Pluses and Minuses

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low grade soft-tissue malignancy associated with a high risk for local recurrence and widespread subclinical extension. Imatinib, a selective tyrosine kinase inhibitor, has been a beneficial adjuvant therapy in patients with unresectable, recurrent, or metastatic DFSP. Because of its characteristic infiltrative growth, effective surgical excision of DFSP may be limited by the risk for disfigurement or functional impairment. In recent cases, neoadjuvant imatinib mesylate therapy has been shown to reduce preoperative tumor size and lessen surgical morbidity associated with the removal of residual DFSP. Use of neoadjuvant imatinib before surgery, however, requires appropriate patient selection and careful weighing of the potential risks and benefits of this treatment.

Abstract

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low grade soft-tissue malignancy associated with a high risk for local recurrence and widespread subclinical extension. Imatinib, a selective tyrosine kinase inhibitor, has been a beneficial adjuvant therapy in patients with unresectable, recurrent, or metastatic DFSP. Because of its characteristic infiltrative growth, effective surgical excision of DFSP may be limited by the risk for disfigurement or functional impairment. In recent cases, neoadjuvant imatinib mesylate therapy has been shown to reduce preoperative tumor size and lessen surgical morbidity associated with the removal of residual DFSP. Use of neoadjuvant imatinib before surgery, however, requires appropriate patient selection and careful weighing of the potential risks and benefits of this treatment.

Dermatofibrosarcoma protuberans (DFSP) is a rare soft-tissue malignancy of cutaneous mesenchymal cell origin representing less than 0.1% of all cancers.1,2 DFSP is characterized by slow, infiltrative growth with substantial local invasion. Broad subclinical extension is common, with infiltration of subcutaneous tissue, fascia, or muscle. DFSP is associated with a high rate of local recurrence, particularly for tumors of the head and neck. Although DFSP can occur in childhood or congenitally, it predominantly presents in adults between age 20 and 50 years, with lesions most commonly located on the trunk or proximal extremities.35 Tumors classically appear as indurated, erythematous, or skin-colored plaques that may develop nodular or telangiectatic, atrophic areas. Slow clinical progression and difficulty distinguishing DFSP from benign scarring or dermatofibroma histologically can contribute to diagnostic delays.

Classical DFSP rarely metastasizes and is infrequently fatal. Approximately 10% of tumors can transform into a fibrosarcomatous variant with high-grade histology and poorer prognosis because of greater invasive and metastatic potential. For high-risk DFSP, chest radiograph or CT may be performed to exclude pulmonary metastasis, because the lung is the most common site of spread.68 Surgical excision with careful margin evaluation is the preferred treatment for DFSP. Low recurrence rates have been shown after Mohs micrographic surgery (MMS) or wide local excision, with en face margin evaluation performed using complete circumferential peripheral and deep margin assessment.914 However, in surgically difficult cases, complete excision may result in cosmetic deformity or functional disability. Using imatinib mesylate in the neoadjuvant setting may represent a partial solution to this problem in properly selected patients.

Molecular Pathogenesis of DFSP

The primary cytogenetic aberration detected in more than 90% of patients with DFSP involves a reciprocal chromosomal translocation between chromosomes 17 and 22, often with formation of supernumerary ring chromosomes. This rearrangement fuses the type I alpha I collagen gene (COL1A1), encoding the most abundant protein in the body, and the beta chain of platelet-derived growth factor (PDGFB) gene, generating amplified expression of PDGFB. Overstimulation of the cell-surface receptor tyrosine kinase PDGF receptor (PDGFR) by its ligand PDGFB, a potent growth factor, is thought to contribute to tumorigenesis.1517 No correlation exists between COL1A1 breakpoints and any particular clinical or histopathologic characteristics.18,19

Imatinib in the Treatment of DFSP

Understanding the molecular pathogenesis of DFSP serves as a basis for targeted therapy using imatinib, a selective tyrosine kinase inhibitor (TKI) with efficacy against the tyrosine kinase receptors PDGFR, KIT, and Abl/Bcr-Abl.20 First approved by the FDA in 2001 for chronic myelogenous leukemia (CML), imatinib's approved useage was expanded in 2006 to include single-agent or adjuvant treatment for patients with unresectable, recurrent, or metastatic DFSP at a dose of 800 mg daily.21 Single-agent or adjuvant imatinib is also cited as an alternative to conventional chemotherapy and radiation therapy in the 2010 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Dermatofibrosarcoma Protuberans (to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org).22

A limited number of case reports and series have shown that imatinib can induce partial or complete regression of DFSP in approximately one half to two thirds of patients treated for FDA-approved indications. In fact, this drug offers a comparatively effective adjuvant option for patients with difficult DFSPs, considering that conventional chemotherapy is largely considered to be ineffective and radiation therapy can induce new or more aggressive tumors.2326 Recent published data from 2 phase II clinical trials enrolling patients with locally advanced or metastatic DFSP showed a nearly 50% response rate with no significant difference in efficacy between imatinib doses of 400 and 800 mg daily.27 Extrapolating from the cumulative published experience with imatinib for treating DFSP, targeted therapy using other PDGFR-inhibiting TKIs may also play a role, especially if advances are made in selectivity, potency, or toxicity.

Cytogenetic confirmation using fluorescence insitu hybridization or reverse-transcriptase polymerase chain reaction may be used to confirm the diagnosis of DFSP or the presence of selected tyrosine kinase receptors in preparation for molecular targeted therapy with imatinib.18,19,28 Tumors without evidence of the t(17;22) chromosomal translocation or that do not depend on PDGFR signaling for growth do not respond to imatinib. Pretreatment testing for the presence of t(17;22) may indicate the potential for a clinical response.24,29

Role for Neoadjuvant Imatinib

Preoperative off-label imatinib therapy may yield partial responses with greater potential for a surgical cure in selected patients with DFSP. Of 16 patients in an EORTC study treated for 14 weeks with 800 mg daily of neoadjuvant imatinib, 4 achieved complete remission after wide local excision.27 Han et al.30 reported clinical responses with a mean decrease of 36.9% in preoperative tumor sizes and 100% local control up to 4 years after MMS in a small series of 4 patients who had taken 800 mg daily of imatinib for 3 months before surgery. Reduction in the clinically apparent tumor size and thickness corresponded with histologic findings of markedly decreased cellularity characterized by fewer CD34+ cells, along with significant hyalinization of dermal collagen (Figure 1). A similar effect has been seen using neoadjuvant imatinib in the treatment of gastrointestinal stromal tumors, and is likely the result of apoptosis.3032 Case reports and data culled from phase II trials featuring small case series have substantiated the use of neoadjuvant imatinib in facilitating complete surgical excision through shrinking the tumor burden.3337

Potential Pluses and Minuses of Neoadjuvant Imatinib

When undertaking preoperative neoadjuvant therapy with imatinib, the objective is to reduce tumor size for surgically challenging cases, including when the tumor is located in an area of cosmetic or functional significance or when incomplete excision is anticipated, which would result in a high risk of local recurrence. For properly selected patients, neoadjuvant imatinib may minimize the chance for disfigurement and enhance the possibility of a surgical cure. Although studies of limited numbers of patients suggest that neoadjuvant imatinib can be effective, long-term outcomes with respect to local margin control and disease-free survival are unknown. The limitations of collecting randomized, prospective clinical data for rare malignancies such as DFSP can be formidable. The decreased cellularity and hyalinization detected histologically after treatment with imatinib also raises the theoretical possibility of discontiguous inhibitory effects resulting from neoadjuvant imatinib treatment, with subsequent generation of skip lesions that could obscure identification of the true negative margin. This concern has not as yet been supported by data in the published literature or observed in patients treated with neoadjuvant imatinib for DFSP who were followed for up to 4 years after MMS.3034

Figure 1
Figure 1

(A) The recurrent lesion on the scalp before imatinib therapy, measuring 7.3 × 6.5 cm. (B) A specimen from the center of the lesion before imatinib therapy, showing spindle cells in a storiform pattern typical of dermatofibrosarcoma protuberans (hematoxylin-eosin, original magnification X20). (C) The lesion size was reduced to 7.0 × 5.5 cm after a 3 month course of imatinib 400 mg twice daily. (D) A specimen from the center of the tumor after imatinib therapy showing decreased cellularity as well as significant hyalinization (hematoxylin-eosin, original magnification X20).

From Han A, Chen EH, Niedt G, et al. Neoadjuvant imatinib therapy for dermatofibrosarcoma protuberans. Arch Dermatol 2009;145:792–796, with permission.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 8, 8; 10.6004/jnccn.2010.0065

Although imatinib is generally well-tolerated with a favorable therapeutic index, each patient should be evaluated for pharmacologic benefits and risk of toxicity. Most adverse effects are mild and seldom limit the tolerability of the drug. Gastrointestinal irritation, fatigue, myalgias, peripheral edema, xerosis, and a maculopapular skin eruption (particularly in older patients) are most commonly encountered. Hematologic toxicity, which is fortunately less frequently observed, may be evaluated through serial complete blood cell counts. Monitoring of weight changes may help identify drug-induced edema. Serious adverse effects are rare, but severe edema, medication-induced cutaneous eruptions, such as Stevens-Johnson Syndrome, and organ failure have all been reported.21,38

Although imatinib is an uncommon cause of heart failure, cardiac safety is a special consideration in a small number of older patients with preexisting cardiac conditions. In addition to evaluating patient comorbidities, a careful medication history is important to assess potential drug interactions. Imatinib is primarily metabolized by the cytochrome P450 (CYP) 3A4 enzyme system. Concentrations of common drugs metabolized by these liver enzymes may therefore increase and the plasma level of imatinib may be altered. Careful monitoring or dosage adjustment is essential in the setting of hepatic impairment. Because targets, including PDGFR, are involved in bone metabolism, long-term use of imatinib may induce osteogenesis.21,38 An advantage of a limited course of imatinib as neoadjuvant therapy is that toxicities associated with long-term use may be avoided, but the ideal dose and duration of preoperative treatment is still unknown. Importantly, the potential teratogenicity of imatinib in animal studies limits its use in pregnancy and during lactation. Finally, as shown in the treatment of CML, measuring trough plasma concentrations of imatinib and maintaining an appropriate circulating dosage may correspond with improved clinical outcomes because drug bioavailability can vary.39 A multidisciplinary management approach facilitates safe use and monitoring in patients taking this drug.

Appropriate patient selection involves careful consideration of various factors. Tumor determinants include DFSP size, location, subtype, and the feasibility of complete excision. Small, low-grade tumors or tumors located in areas with significant skin and soft tissue laxity do not generally require neoadjuvant therapy, because surgical excision is straightforward to perform in these cases. For large or recurrent lesions, tumors on the head and neck, or those in proximity to critical structures may be good settings for neoadjuvant therapy with imatinib, particularly if an opportunity exists to preserve function or improve the likelihood of negative margins after surgery. If there is a chance that surgical treatment of a larger tumor may be inadequate, neoadjuvant imatinib may be able to reduce the tumor size and theoretically improve tumor resectability.

Conclusions

Insufficient data precludes the endorsement of a single treatment modality for high-risk DFSP. Although limited data are available on the use of imatinib in patients with DFSP, the existing data suggest that this drug may be beneficial as neoadjuvant therapy in properly selected individuals. Additional studies are needed to better elucidate the parameters for patient selection and treatment regimens. Because imatinib has a favorable safety profile, off-label use of this drug in the appropriate setting may mitigate unfavorable cosmetic or functional outcomes and even enhance surgical outcomes, suggesting that its beneficial effects have the potential to significantly outweigh its risks.

The authors have disclosed that they have no financial interests, arrangements, or affiliations with the manufacturers of any products discussed in the article or their competitors.

References

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    CriscioneVDWeinstockMA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol2007;56:968973.

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    MaireGFraitagSGalmicheL. A clinical, histologic, and molecular study of 9 cases of congenital dermatofibrosarcoma protuberans. Arch Dermatol2007;143:203210.

    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    MentzelTBehamAKatenkampD. Fibrosarcomatous (``high-grade'') dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance. Am J Surg Pathol1998;22:576587.

    • Search Google Scholar
    • Export Citation
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    FarmaJMAmmoriJBZagerJS. Dermatofibrosarcoma protuberans: how wide should we resect?Ann Surg Oncol2010;17:21122118.

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    RatnerDThomasCOJohnsonTM. 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 Dermatol1997;37:600613.

    • Search Google Scholar
    • Export Citation
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    GlosterHMJrHarrisKRRoenigkRK. A comparison between Mohs micrographic surgery and wide surgical excision for the treatment of dermatofibrosarcoma protuberans. J Am Acad Dermatol1996;35:8287.

    • Search Google Scholar
    • Export Citation
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    SnowSNGordonEMLarsonPO. Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature. Cancer2004;101:2838.

    • Search Google Scholar
    • Export Citation
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    HancoxJGKelleyBGreenwayHTJr. Treatment of dermatofibroma sarcoma protuberans using modified Mohs micrographic surgery: no recurrences and smaller defects. Dermatol Surg2008;34:780784.

    • Search Google Scholar
    • Export Citation
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    PedeutourFCoindreJMSozziG. Supernumerary ring chromosomes containing chromosome 17 sequences. A specific feature of dermatofibrosarcoma protuberans? Cancer Genet Cytogenet1994;76:19.

    • Search Google Scholar
    • Export Citation
  • 16.

    NaeemRLuxMLHuangSF. Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22. Am J Pathol1995;47:15531558.

    • Search Google Scholar
    • Export Citation
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    ShimizuAO'BrienKPSjoblomT. 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 Res1999;59:37193723.

    • Search Google Scholar
    • Export Citation
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    PatelKUSzaboSSHernandezVS. 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 Pathol2008;39:184193.

    • Search Google Scholar
    • Export Citation
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    LlombartBSanmartinOLopez-GuerreroJA. Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1-PDGFB) study with therapeutic implications. Histopathology2009;54:860872.

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    • Export Citation
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    • Search Google Scholar
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    LemmDMuggeLOMentzelTHoffkenK. Current treatment options in dermatofibrosarcoma protuberans. J Cancer Res Clin Oncol2009;135:653665.

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    McArthurGA. Molecular targeting of dermatofibrosarcoma protuberans: a new approach to a surgical disease. J Natl Compr Canc Netw2007;5:557562.

    • Search Google Scholar
    • Export Citation
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    McArthurG. Dermatofibrosarcoma protuberans: recent clinical progress. Ann Surg Oncol2007;14:28762886.

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    • Search Google Scholar
    • Export Citation
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    HaycoxCLOdlandPBOlbrichtSMPiepkornM. Immunohistochemical characterization of dermatofibrosarcoma protuberans with practical applications for diagnosis and treatment. J Am Acad Dermatol1997;37(3 Pt 1):438444.

    • Search Google Scholar
    • Export Citation
  • 29.

    MakiRGAwanRADixonRH. Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans. Int J Cancer2002;100:623626.

    • Search Google Scholar
    • Export Citation
  • 30.

    HanAChenEHNiedtG. Neoadjuvant imatinib therapy for dermatofibrosarcoma protuberans. Arch Dermatol2009;145:792796.

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    SciotRDebiec-RychterM. GIST under imatinib therapy. Semin Diagn Pathol2006;23:8490.

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    ThomisonJMcCarterMMcClainD. Hyalinized collagen in a dermatofibrosarcoma protuberans after treatment with imatinib mesylate. J Cutan Pathol2008;35:10031006.

    • Search Google Scholar
    • Export Citation
  • 33.

    McArthurGADemetriGDvan OosteromA. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol2005;23:866873.

    • Search Google Scholar
    • Export Citation
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    MehranyKSwansonNAHeinrichMC. Dermatofibrosarcoma protuberans: a partial response to imatinib therapy. Dermatol Surg2006;32:456459.

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    WrightTIPetersenJE. Treatment of recurrent dermatofibrosarcoma protuberans with imatinib mesylate, followed by Mohs micrographic surgery. Dermatol Surg2007;33:741744.

    • Search Google Scholar
    • Export Citation
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    LemmDMueggeLOHoeffkenK. Remission with Imatinib mesylate treatment in a patient with initially unresectable dermatofibrosarcoma protuberans—a case report. Oral Maxillofac Surg2008;12:209213.

    • Search Google Scholar
    • Export Citation
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Correspondence: Hillary Johnson-Jahangir, MD, PhD, Columbia University Medical Center, Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032. E-mail: hj2256@columbia.edu
  • View in gallery

    (A) The recurrent lesion on the scalp before imatinib therapy, measuring 7.3 × 6.5 cm. (B) A specimen from the center of the lesion before imatinib therapy, showing spindle cells in a storiform pattern typical of dermatofibrosarcoma protuberans (hematoxylin-eosin, original magnification X20). (C) The lesion size was reduced to 7.0 × 5.5 cm after a 3 month course of imatinib 400 mg twice daily. (D) A specimen from the center of the tumor after imatinib therapy showing decreased cellularity as well as significant hyalinization (hematoxylin-eosin, original magnification X20).

    From Han A, Chen EH, Niedt G, et al. Neoadjuvant imatinib therapy for dermatofibrosarcoma protuberans. Arch Dermatol 2009;145:792–796, with permission.

  • 1.

    MoriTMisagoNYamamotoO. Expression of nestin in dermatofibrosarcoma protuberans in comparison to dermatofibroma. J Dermatol2008;35:419425.

    • Search Google Scholar
    • Export Citation
  • 2.

    CriscioneVDWeinstockMA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol2007;56:968973.

    • Search Google Scholar
    • Export Citation
  • 3.

    GlosterHMJr. Dermatofibrosarcoma protuberans. J Am Acad Dermatol1996;35(3 Pt 1):355374; quiz 375–376.

  • 4.

    WeinsteinJMDroletBAEsterlyNB. Congenital dermatofibrosarcoma protuberans: variability in presentation. Arch Dermatol2003;139:207211.

    • Search Google Scholar
    • Export Citation
  • 5.

    MaireGFraitagSGalmicheL. A clinical, histologic, and molecular study of 9 cases of congenital dermatofibrosarcoma protuberans. Arch Dermatol2007;143:203210.

    • Search Google Scholar
    • Export Citation
  • 6.

    BowneWBAntonescuCRLeungDH. Dermatofibrosarcoma protuberans: a clinicopathologic analysis of patients treated and followed at a single institution. Cancer2000;88:27112720.

    • Search Google Scholar
    • Export Citation
  • 7.

    FioreMMiceliRMussiC. Dermatofibrosarcoma protuberans treated at a single institution: a surgical disease with a high cure rate. J Clin Oncol2005;23:76697675.

    • Search Google Scholar
    • Export Citation
  • 8.

    MentzelTBehamAKatenkampD. Fibrosarcomatous (``high-grade'') dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance. Am J Surg Pathol1998;22:576587.

    • Search Google Scholar
    • Export Citation
  • 9.

    DuBayDCimminoVLoweL. Low recurrence rate after surgery for dermatofibrosarcoma protuberans: a multidisciplinary approach from a single institution. Cancer2004;100:10081016.

    • Search Google Scholar
    • Export Citation
  • 10.

    FarmaJMAmmoriJBZagerJS. Dermatofibrosarcoma protuberans: how wide should we resect?Ann Surg Oncol2010;17:21122118.

  • 11.

    RatnerDThomasCOJohnsonTM. 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 Dermatol1997;37:600613.

    • Search Google Scholar
    • Export Citation
  • 12.

    GlosterHMJrHarrisKRRoenigkRK. A comparison between Mohs micrographic surgery and wide surgical excision for the treatment of dermatofibrosarcoma protuberans. J Am Acad Dermatol1996;35:8287.

    • Search Google Scholar
    • Export Citation
  • 13.

    SnowSNGordonEMLarsonPO. Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature. Cancer2004;101:2838.

    • Search Google Scholar
    • Export Citation
  • 14.

    HancoxJGKelleyBGreenwayHTJr. Treatment of dermatofibroma sarcoma protuberans using modified Mohs micrographic surgery: no recurrences and smaller defects. Dermatol Surg2008;34:780784.

    • Search Google Scholar
    • Export Citation
  • 15.

    PedeutourFCoindreJMSozziG. Supernumerary ring chromosomes containing chromosome 17 sequences. A specific feature of dermatofibrosarcoma protuberans? Cancer Genet Cytogenet1994;76:19.

    • Search Google Scholar
    • Export Citation
  • 16.

    NaeemRLuxMLHuangSF. Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22. Am J Pathol1995;47:15531558.

    • Search Google Scholar
    • Export Citation
  • 17.

    ShimizuAO'BrienKPSjoblomT. 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 Res1999;59:37193723.

    • Search Google Scholar
    • Export Citation
  • 18.

    PatelKUSzaboSSHernandezVS. 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 Pathol2008;39:184193.

    • Search Google Scholar
    • Export Citation
  • 19.

    LlombartBSanmartinOLopez-GuerreroJA. Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1-PDGFB) study with therapeutic implications. Histopathology2009;54:860872.

    • Search Google Scholar
    • Export Citation
  • 20.

    CapdevilleRSilbermanS. Imatinib: a targeted clinical drug development. Semin Hematol2003;40(2 Suppl 2):1520.

  • 21.

    Gleevec (imatinib mesylate). U.S. Food and Drug Administration Web site. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=GLEEVEC. Accessed April 7 2010.

  • 22.

    MillerSJAlamMAndersenJ. NCCN clinical practice guidelines in oncology: dermatofibrosarcoma protuberans. Version 12010. Available at:http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed April 7 2010.

    • Search Google Scholar
    • Export Citation
  • 23.

    LemmDMuggeLOMentzelTHoffkenK. Current treatment options in dermatofibrosarcoma protuberans. J Cancer Res Clin Oncol2009;135:653665.

  • 24.

    McArthurGA. Molecular targeting of dermatofibrosarcoma protuberans: a new approach to a surgical disease. J Natl Compr Canc Netw2007;5:557562.

    • Search Google Scholar
    • Export Citation
  • 25.

    McArthurG. Dermatofibrosarcoma protuberans: recent clinical progress. Ann Surg Oncol2007;14:28762886.

  • 26.

    AbramsTASchuetzeSM. Targeted therapy for dermatofibrosarcoma protuberans. Curr Oncol Rep2006;8:291296.

  • 27.

    RutkowskiPVan GlabbekeMRankinCJ. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol2010;28:17721779.

    • Search Google Scholar
    • Export Citation
  • 28.

    HaycoxCLOdlandPBOlbrichtSMPiepkornM. Immunohistochemical characterization of dermatofibrosarcoma protuberans with practical applications for diagnosis and treatment. J Am Acad Dermatol1997;37(3 Pt 1):438444.

    • Search Google Scholar
    • Export Citation
  • 29.

    MakiRGAwanRADixonRH. Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans. Int J Cancer2002;100:623626.

    • Search Google Scholar
    • Export Citation
  • 30.

    HanAChenEHNiedtG. Neoadjuvant imatinib therapy for dermatofibrosarcoma protuberans. Arch Dermatol2009;145:792796.

  • 31.

    SciotRDebiec-RychterM. GIST under imatinib therapy. Semin Diagn Pathol2006;23:8490.

  • 32.

    ThomisonJMcCarterMMcClainD. Hyalinized collagen in a dermatofibrosarcoma protuberans after treatment with imatinib mesylate. J Cutan Pathol2008;35:10031006.

    • Search Google Scholar
    • Export Citation
  • 33.

    McArthurGADemetriGDvan OosteromA. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol2005;23:866873.

    • Search Google Scholar
    • Export Citation
  • 34.

    MehranyKSwansonNAHeinrichMC. Dermatofibrosarcoma protuberans: a partial response to imatinib therapy. Dermatol Surg2006;32:456459.

  • 35.

    WrightTIPetersenJE. Treatment of recurrent dermatofibrosarcoma protuberans with imatinib mesylate, followed by Mohs micrographic surgery. Dermatol Surg2007;33:741744.

    • Search Google Scholar
    • Export Citation
  • 36.

    LemmDMueggeLOHoeffkenK. Remission with Imatinib mesylate treatment in a patient with initially unresectable dermatofibrosarcoma protuberans—a case report. Oral Maxillofac Surg2008;12:209213.

    • Search Google Scholar
    • Export Citation
  • 37.

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