Dermatofibrosarcoma protuberans (DFSP) is a rare dermal soft tissue sarcoma characterized by a typically indolent clinical course. The greatest clinical challenge in management of DFSP is achieving local control. There is vigorous debate in the literature as to the optimal surgical approach to these tumors. The choice between wide local excision and Mohs micrographic surgery for DFSP should be governed by the attainment of three goals: (1) to completely excise the tumor with negative margins, tantamount to cure; (2) to preserve function, optimize cosmesis, and minimize morbidity of resection; and (3) to minimize cost and inconvenience to the patient and the health care system at large.
Key points
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Dermatofibrosarcoma protuberans (DFSP) is a rare dermal soft tissue sarcoma characterized by a typically indolent clinical course.
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Complete surgical resection is the mainstay of treatment, and this is accomplished with either a standard wide local excision (WLE) or with Mohs micrographic surgery (MMS), as long as a comprehensive pathologic examination of the margins is completed before reconstruction of the defect.
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MMS is the ideal surgical approach for relatively small DFSPs in cosmetically sensitive areas (ie, face, scalp, or neck), where tissue preservation is critical to achieve optimal cosmetic and functional outcomes.
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WLE with a 1.0- to 1.5-cm margin width is the ideal approach for most DFSPs on the trunk or extremities, because it is likely to achieve complete tumor clearance with excellent cosmetic and functional outcomes in a single stage.
Introduction
Dermatofibrosarcoma protuberans (DFSP) is a rare dermal soft tissue sarcoma characterized by a typically indolent clinical course. Although transformation to a high-grade fibrosarcoma is possible, particularly in the case of recurrent DFSP, by far the greatest clinical challenge in the management of DFSP is achieving local control. Because DFSP arises in the dermis and invades radially through preexisting collagen bundles and deeply along connective tissue septae, its extent of invasion is often difficult to clinically appreciate, and thus determining the appropriate width of the margins of resection is challenging. There has been vigorous debate in the literature as to the optimal surgical approach to these tumors, with some groups advocating for radical resection with defined margins of excision, and others advocating for Mohs micrographic surgery (MMS).
Ultimately, there is no “one size fits all” surgical technique for the treatment of DFSP. Indeed, the choice between wide local excision (WLE) and MMS for DFSP should be governed by the attainment of the following three goals: (1) to completely excise the tumor with negative margins, which is tantamount to cure, because these tumors very rarely metastasize; (2) to preserve function, optimize cosmesis, and minimize the morbidity of resection; and (3) to minimize the cost and inconvenience to the patient and the health care system at large. Both WLE and MMS are capable of achieving the first goal, such that the choice of surgical approach may be driven more by individual patient and tumor factors that make the attainment of the second and third goals important.
Introduction
Dermatofibrosarcoma protuberans (DFSP) is a rare dermal soft tissue sarcoma characterized by a typically indolent clinical course. Although transformation to a high-grade fibrosarcoma is possible, particularly in the case of recurrent DFSP, by far the greatest clinical challenge in the management of DFSP is achieving local control. Because DFSP arises in the dermis and invades radially through preexisting collagen bundles and deeply along connective tissue septae, its extent of invasion is often difficult to clinically appreciate, and thus determining the appropriate width of the margins of resection is challenging. There has been vigorous debate in the literature as to the optimal surgical approach to these tumors, with some groups advocating for radical resection with defined margins of excision, and others advocating for Mohs micrographic surgery (MMS).
Ultimately, there is no “one size fits all” surgical technique for the treatment of DFSP. Indeed, the choice between wide local excision (WLE) and MMS for DFSP should be governed by the attainment of the following three goals: (1) to completely excise the tumor with negative margins, which is tantamount to cure, because these tumors very rarely metastasize; (2) to preserve function, optimize cosmesis, and minimize the morbidity of resection; and (3) to minimize the cost and inconvenience to the patient and the health care system at large. Both WLE and MMS are capable of achieving the first goal, such that the choice of surgical approach may be driven more by individual patient and tumor factors that make the attainment of the second and third goals important.
Epidemiology
DFSP is a rare sarcoma, accounting for less than 0.1% of all malignancies and between 2% and 6% of all soft tissue sarcomas, although it is the most common sarcoma of the skin. Rouhani and colleagues, in an analysis of the Surveillance, Epidemiology, and End Results database from 1992 to 2004, reported that the incidence of DFSP was 4.5 cases per million person-years and that DFSP comprised 18.4% of all cutaneous sarcomas during that time period. It typically occurs in the third and fourth decades of life, has an equal gender distribution, and has a higher incidence among black persons than seen for other cutaneous sarcomas.
Clinical presentation and natural history
DFSP most commonly presents as a slow-growing, asymptomatic nodular or plaque-like lesion that may have a violaceous or reddish brown appearance. The tumor has a hard consistency and is fixed to the dermis but is usually freely movable over the underlying fascia and muscle. Over time, which can vary from months to years, DFSP may grow radially to generate a larger plaque and vertically to generate multiple nodules within the plaque, from which its name “protuberans” is derived. The average tumor diameter is on the order of a few centimeters, although neglected tumors can grow to much larger sizes. DFSP can occur anywhere on the body, although the most common locations are the extremities, trunk, and head and neck. Diagnostic delays are common with these tumors, which are often mistaken as dermatofibromas, sebaceous cysts, lipomas, and scars.
Despite the frequent, long delays in diagnosis, distant metastasis is exceedingly rare, with a reported rate of 2% to 4%. The main site of distant recurrence is the lung, via hematogenous tumor spread, and in nearly all cases metastases are preceded by multiple local recurrences or in the context of transformation to a higher-grade fibrosarcoma. As with most other soft tissue sarcomas, DFSP rarely metastasizes to the regional lymph nodes, having been reported to occur in 1% or fewer cases.
Pathology
Grossly, DFSP appears as a solitary, poorly circumscribed, gray-white mass that infiltrates the dermis and subcutaneous tissue ( Fig. 1 ). Histologically, the tumor is composed of a dense, uniform array of cells with spindle-shaped nuclei embedded within collagen and may demonstrate a cartwheel or storiform pattern. Tumor cells have large nuclei with low pleomorphism and rare mitotic figures. A defining characteristic of DFSP is its capacity to invade the surrounding tissues to a considerable distance, with tumor cells forming tentacle-like projections along the fibrous septae and into fat lobules in a distinctive honeycomb pattern ( Fig. 2 ). Notably, this infiltration is often eccentric, with long, narrow tumor extensions in one direction but not in another, making it difficult to determine the true extent of the lesion.
There are several histologic subtypes of DFSP, including pigmented (Bednar tumor), myxoid, sclerosing, granular cell, atrophic, and giant cell fibroblastoma variants. Approximately 80% to 90% of DFSPs are low-grade lesions, whereas the remaining 10% to 20% of DFSPs contain a high-grade fibrosarcomatous (DFSP-FS) component classically showing a “herringbone” pattern with hypercellularity, atypical cells, and an increased mitotic rate ( Fig. 3 ). This histologic variant is associated with a more aggressive clinical behavior, with a higher rate of local recurrence after resection and an increased risk of distant metastasis.
Immunohistochemical expression of the CD34 antigen is the most helpful diagnostic marker of DFSP ( Fig. 4 ), and immunostaining for CD34 and factor XIIIa may be necessary to distinguish a DFSP from a benign dermatofibroma, respectively. However, CD34 expression is by no means specific for DFSP and may be absent in a significant percentage of these tumors, including in DFSP-FS.
Molecular biology and pathogenesis
Advances in understanding the molecular pathogenesis of DFSP have enabled the diagnosis of most of these tumors using modern molecular pathologic techniques. Genetically, DFSP is characterized by either a reciprocal translocation [t(17;22)] or, more often, by a supernumerary ring chromosome [r(17;22)] involving chromosomes 17 and 22. These chromosomal rearrangements lead to a fusion of the collagen type Iα1 ( COL1A1 ) gene on chromosome 17 and the platelet-derived growth factor β ( PDGFB ) gene on chromosome 22, which leads to constitutive activation of the PDGFB receptor and its tyrosine kinases that results in cell growth and proliferation. The chromosomal translocation is detected by fluorescence in situ hybridization, and although this study is not absolutely necessary for the routine pathologic diagnosis of DFSP, identification of the COL1A1/PDGFB rearrangement is mandatory in cases where standard pathologic studies are inconclusive.
Management of dermatofibrosarcoma protuberans: overview
The diagnostic work-up of DFSP entails a complete history and physical examination. Radiographic imaging of the primary tumor is generally not necessary, especially in the case of small tumors. However, for larger tumors in difficult locations, MRI may be helpful. Because the risk of metastasis is very low, staging scans of the chest or other sites are generally not indicated unless there are worrisome findings on the history and physical examination or high-risk features on pathology. Patients with larger tumors and/or tumors in cosmetically sensitive areas may benefit from a multidisciplinary approach to optimize the clinical and reconstructive outcomes.
Complete surgical resection is the mainstay of treatment, and this is accomplished with either a standard WLE or with MMS, as long as a comprehensive pathologic examination of the margins is completed before reconstruction of the defect. In the occasional circumstance when a surgical margin is positive or very narrow and further surgical resection is not possible, adjuvant radiation therapy may be considered. In the case of locally advanced or recurrent DFSP, neoadjuvant imatinib mesylate (Gleevec) therapy has been shown to reduce the preoperative tumor size and to lessen surgical morbidity associated with the resection of residual DFSP. Indeed, because the pathogenesis of DFSP is caused by activation of the PDGFRB receptor, which has tyrosine kinase activity, it makes perfect sense that tyrosine kinase inhibitors, such as imatinib, would have activity in DFSP. Conventional chemotherapy, however, is generally considered ineffective in the treatment of DFSP.
Surgical treatment: wide local excision
WLE down to and including the underlying fascia has long been the standard surgical approach to DFSP, and in most cases this is all that is required. However, the optimal width of excision around the primary tumor has never been defined in prospective studies. Older retrospective studies describing 1- to 3-cm margins of excision report local recurrence rates of 50% or more. Such high recurrence rates are thought to be caused by the extensive and eccentric pattern of local invasion of DFSP, which is difficult to appreciate at the time of resection, making it difficult to do a margin-negative excision. Thus, even lesions that have been said to have been excised with “negative” margins exhibit high rates of local recurrence. More recent large series evaluating WLE for DFSP have advocated for margin widths ranging from 1 cm to greater than or equal to 3 cm, with positive margin rates and local recurrence rates ranging from 3% to 32% and 0% to 50%, respectively ( Table 1 ).
| Authors/Year | Patient (N) | Margin Width (cm) | Negative Margins (%) | Positive Margins (%) | Local Recurrence (%) |
|---|---|---|---|---|---|
| Bowne et al, 2000 | 159 | NA | 58 | 32 | 21 |
| Chang et al, 2004 | 60 | ≥3.0 | NA | NA | 16 |
| DuBay et al, 2004 | 43 | 1–2 | 95 | 5 | 0 |
| Khatri et al, 2003 | 24 | 2.5–3.3 | 100 | 0 | 0 |
| Fiore et al, 2005 | 136 primary | NA | 88 | 12 | 4 |
| 82 recurrent | NA | 85 | 15 | 5 | |
| Monnier et al, 2006 | 4 | <0.9 | NA | NA | 50 |
| 31 | 1–2.9 | NA | NA | 46 | |
| 31 | ≥3.0 | NA | NA | 7 | |
| Kimmel et al, 2007 | 98 | 2.0 | NA | NA | 41 |
| — | 2.5 | NA | NA | 24 | |
| — | 3.0 | NA | NA | 11–20 | |
| Popov et al, 2007 | 40 | 1.5–6.0 | 100 | 0 | 0 |
| Yu et al, 2008 | 25 | 3.0 | NA | NA | 0 |
| Paradisi et al, 2008 | 38 | 2–5 | NA | NA | 13 |
| Meguerditchian et al, 2010 | 28 | 2.0 | 79 | 21 | 3.6 |
| Heuvel et al, 2010 | 38 | 2–3 | 95 | 5 | 7 |
| Farma et al, 2010 | 206 | 2 (median) | 97 | 3 | 1 |
| Cai et al, 2012 | 81 | 1.5–2.5 | NA | NA | 13.6 |
| 141 | ≥3.0 | — | — | 5.7 | |
| Woo et al, 2016 | 21 | <3.0 | 95 | 5 | 0 |
| 28 | ≥3.0 | 96 | 4 | 0 | |
| Kim et al, 2015 | 90 | 1–5 | 100 | 0 | 5.5 |
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