Dermatofibrosarcoma protuberans

Published on 19/03/2015 by admin

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Last modified 22/04/2025

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Dermatofibrosarcoma protuberans

Hooman Khorasani and Kate Kleydman

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade soft-tissue undifferentiated mesenchymal tumor that arises in the dermis and invades deeper underlying soft tissue. It is associated with a high risk for local recurrence and widespread subclinical extension. The incidence of DFSP is 0.1% of all cancers and 1.8% of all soft tissue sarcomas. It occurs most often in adults aged 20–50 years; pediatric and infantile cases, particularly congenital ones, are much less frequent. The tumor most commonly involves the trunk (50–60%) and upper limbs (25%); head and neck sites account for 10–15% of DFSP cases. If left untreated, the tumor grows slowly, invading surrounding tissue as well as neurovascular bundles. Although DFSP can be locally destructive the tumor rarely metastasizes.

Management strategy

Surgical excision remains the mainstay of treatment for DFSP. Since DFSP commonly has an infiltrating growth pattern and extends far beyond the clinical margins, a wide excision of 2–3 cm or more of the margins beyond clinically identifiable tumor border, down to and including the fascia, is recommended. 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.

Since these neoplasms have a high tendency to recur locally after surgical excision, 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. Mohs surgery with continuous histological margin control requires less tissue removal, allows complete margin assessment, low recurrence rates and is rapidly emerging as a first-line treatment modality for this condition.

Alternatively, some dermatologic surgeons have adopted modified Mohs techniques, or so-called ‘slow Mohs,’ by using rush paraffin sections instead of a fresh tissue technique.

Cytogenetically, DFSP is characterized by a t(17;22)(22;q13) aberration with fusion of the collagen type 1α (COL1A1) gene on chromosome 17 with the platelet-derived growth factor-β (PDGFB) gene on chromosome 22, which renders these tumors responsive to targeted therapy with tyrosine kinase inhibitors, such as imatinib mesylate. Originally approved for the treatment of chronic myelogenic leukemia, imatinib mesylate has been found to have significant therapeutic value in the treatment of DFSP. In 2006, the FDA granted approval for imatinib mesylate (Gleevac) as a single agent for the treatment of adult patients with unresectable, recurrent, and/or metastatic DFSP. The recommended oral dose is 800 mg/day. Before starting imatinib therapy, cytogenetic studies to confirm PDGFB gene rearrangement may be necessary for predicting the clinical response.

Neoadjuvant imatinib therapy for DFSP has also been proposed in recent studies. It has been used as a preoperative therapy agent in locally advanced or recurrent DFSPs. This therapeutic strategy may decrease tumor load, promote tumor cell apoptosis, and subsequently reduce the extent of surgery.

Adjuvant radiotherapy, administered either before or after surgery, significantly reduces the risk of local recurrence in patients who have or who are likely to have close or positive margins. This appears to be true for radiation alone or postoperatively for margin-positive disease (primary or recurrent).

DFSP is a radioresponsive tumor and radiation to doses of 50–60 Gy should be considered. Radiation is not recommended in younger patients (under age of 50, because of increased risk of radiodermatitis and scarring) or in patients with a previous history of radiation therapy. Radiation is also contraindicated in patients with connective tissue diseases or genetic conditions predisposing to skin cancer (e.g., patients with Gorlin syndrome or xeroderma pigmentosum). Combined conservation resection and postoperative radiation should also be considered for situations where adequate wide excision alone would result in major cosmetic or functional deficits.

Specific investigations

First-line therapies

imageMohs micrographic surgery B
imageWide local excision C

Second-line therapies

imageImatinib mesylate (Gleevac) B
imageRadiation B

Advanced dermatofibrosarcoma protuberans treated with imatinib mesylate.

Zhu JH, Li QW, Xiao WH, Sun JZ, Wang RL, Lu JY. Zhonghua Zhong Liu Za Zhi J 2011; 33: 470–2.

Twenty-four cases of advanced DFSP diagnosed by pathology and treated were included in this study. The patients were treated with imatinib mesylate (400 mg oral daily) and observed for treatment efficacy, side effects, and survival time. The disease control rate (DCR = complete remission + partial remission + stable disease) was 83.3%. The median response time in 18 cases was 5.6 months. The median survival time in 20 cases with disease control was 30 months; however, in non-responsive cases it was only 10 months. Side effects related to imatinib mesylate included nausea and vomiting (20.8%), neutropenia (12.5%), and edema (8.3%).

Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: results of a multicenter phase II study on 25 patients.

Kérob D, Porcher R, Vérola O, Dalle S, Maubec E, Aubin F, et al. Clin Cancer Res 2010; 16: 3288–95.

Twenty-five adults suffering from primary or recurrent DFSP were included in a phase II multicenter study. Percentage of clinical response was defined to a 2-month preoperative daily administration of 600 mg of imatinib mesylate before wide local excision. A clinical response was achieved in nine (36%) patients (95% CI: 18.9–57.5). The median relative tumoral decrease was 20.0% (range, −12.5 to 100). Apart from expected grade II or III side effects, one grade III neutropenia, one grade III maculopapular rash, and one grade IV transient transaminitis were observed.

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