Overview
The NCCN Non-Melanoma Skin Cancer Panel has developed these guidelines outlining the treatment of dermatofibrosarcoma protuberans (DFSP) to supplement their other guidelines (NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Basal Cell and Squamous Cell Skin Cancers and Merkel Cell Carcinoma; to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org). The NCCN Soft Tissue Sarcoma Panel provided expert input in the development of these guidelines. DFSP is an uncommon, low-grade sarcoma of fibroblast origin with an incidence rate of 4.2 to 4.5 cases per million persons per year in the United States.1,2 It rarely metastasizes. However, initial misdiagnosis, prolonged time to accurate diagnosis, and large
NCCN Clinical Practice Guidelines in Oncology for Dermatofibrosarcoma Protuberans
NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. tumor size at the time of diagnosis are common. Three-dimensional reconstruction of DFSP3 has shown tumors with highly irregular shapes and frequent finger-like extensions.4 As a result, incomplete removal and subsequent recurrence are common. The local recurrence rate for DFSP in studies ranges from 0% to 60%, whereas the rate of development of regional or distant metastatic disease is only 1% and 4% to 5%, respectively.5
Diagnosis
As with all solid tumors, clinical suspicion is confirmed with biopsy. In most cases, examination of hematoxylin and eosin-stained specimens using light microscopy results in an unequivocal diagnosis. However, differentiation of DFSP from dermatofibroma can sometimes be difficult. In these instances, immunostaining with CD34, factor XIIIa, metallothioneins, tenascin, and/or stromelysin-3 may be useful.5–9 Therefore, the panel recommends that appropriate and confirmatory immunostaining be performed in all cases of suspected DFSP. Finally, whether the histologic features of a high mitotic rate or evidence of fibrosarcomatous change (typically in > 5% of the surgical specimen) have prognostic significance in DFSP is unclear. Studies in the biomedical literature both support10,11 and refute12 this notion. Thus, the panel requested that these 2 features be noted in all pathology reports assessing this tumor.
When the clinician’s suspicion for DFSP is high but the initial biopsy does not support the diagnosis, rebiopsy is recommended and may show tumor presence. Multiple nonsupportive or equivocal biopsies over time, before definitive diagnosis, are common in the clinical history for this tumor; thus, DFSP is frequently misdiagnosed. Because metastatic disease is rare, an extensive workup is not routinely indicated unless suggestive aspects in the history and physical examination (H&P) or adverse prognostic histologic features are present. Stage I is local disease, stage II is regional disease, and stage III is distant disease.
NCCN Clinical Practice Guidelines in Oncology: Dermatofibrosarcoma Protuberans Version 1.2012
Version 1.2012, 9-27-11 ©2012 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 10, 3; 10.6004/jnccn.2012.0032
Treatment
Initial treatment of DFSP is surgical. Because of its proclivity for irregular and frequently deep subclinical extensions, every effort should be made to completely remove this tumor at initial therapy. If initial surgery yields positive margins, re-resection is recommended whenever possible, with the goal of achieving clear margins. The surgical approach to DFSP must be meticulously planned. Size and location of the tumor and cosmetic issues will dictate the most appropriate surgical procedure. As noted in the algorithm, some form of complete histologic assessment of all surgical margins before reconstruction is preferred. See the NCCN Guidelines for Soft Tissue Sarcoma for principles of sarcoma surgery (to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org [SARC-C]). Mohs or modified Mohs surgery3,4,13–20 and traditional wide excision,21 typically with 2- to 4-cm margins to investing fascia that are subsequently verified to be clear through traditional pathologic examination, are all methods to achieve complete histologic assessment.14,22,23 In a recent series of 244 patients with DFSP, tumor depth was the only factor associated with disease-free survival in the primary setting, underscoring the importance to excise the deep fascia to remove any infiltrating tumor cells.24 In another retrospective review of 48 patients, positive margins were more frequent with wide excision than with Mohs, but the local recurrence rates were statistically similar (3.6% vs. 0%, respectively; P = 1.0).25 Confirmation of negative margins should precede any reconstruction that requires extensive undermining or tissue movement. If concern exists that the surgical margins are not completely clear, tissue rearrangement should be avoided and split-thickness skin grafting considered to monitor for recurrence.
DFSP is characterized by a translocation between chromosomes 17 and 22 (t(17:22)) resulting in the overexpression of platelet-derived growth factor receptor (PDGFR) β.26–28 These findings suggest that targeting PDGFRs may lead to the development of new therapeutic options for DFSP. In recently published results, imatinib mesylate, a protein tyrosine kinase inhibitor, has shown clinical activity against localized and metastatic DFSP tumors containing t(17:22).29–33 Imatinib mesylate has recently been approved by the FDA for the treatment of unresectable, recurrent, and/or metastatic DFSP in adult patients.34 Because tumors lacking the t(17;22) translocation may not respond to imatinib molecular, analysis with cytogenetics may be useful before initiating imatinib therapy.
Radiation has occasionally been used as a primary therapeutic modality for DFSP,35 but it is more commonly used as adjuvant therapy after surgery.36–38 Postoperative radiation therapy or imatinib mesylate should be considered for positive surgical margins if further resection is not feasible (unresectable disease). If a negative margin is achieved, no adjuvant treatment is necessary.
Recurrent tumors, whenever possible, should be resected. Radiation therapy, if not given previously, or imatinib mesylate should be considered if this is not possible, or if additional resection would lead to unacceptable functional or cosmetic outcomes. Clinical trials, imatinib mesylate, chemotherapy, radiation therapy, or re-resection as feasible under specific clinical circumstances should all be considered in the rare event of metastatic disease.
Several clinical trials are underway for the treatment of DFSP with imatinib (www.ClinicalTrials.gov).
Follow-Up
Finally, given the historically high local recurrence rates for DFSP, ongoing clinical follow-up of the primary site every 6 to 12 months is indicated, with rebiopsy of any suspicious regions. Although metastatic disease is rare, a guided H&P should also be performed, with additional imaging studies as indicated.
Individual Disclosures for the NCCN Guidelines Panel for Dermatofibrosarcoma Protuberans
References
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