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10.1245/ASO.2003.03.581
Annals of Surgical Oncology 10:1118-1122 (2003)
© 2003 Society of Surgical Oncology
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ORIGINAL ARTICLES

Dermatofibrosarcoma Protuberans: Reappraisal of Wide Local Excision and Impact of Inadequate Initial Treatment

Vijay P. Khatri, MD, Joseph M. Galante, MD, Richard J. Bold, MD, Philip D. Schneider, MD, Rajendra Ramsamooj, MD and James E. Goodnight, Jr., MD

From the Division of Surgical Oncology (VPK, JMG, RJB, PDS, JEG) and the Department of Pathology (RR), University of California, Davis Medical Center, Sacramento, California.

Correspondence: Address correspondence and reprint requests to: Vijay P. Khatri, MD, University of California, Davis, Division of Surgical Oncology, 4501 X Street, Suite 3010, Sacramento, CA 95817; Fax: 916-731-5706; E-mail: vijay.khatri{at}ucdmc.ucdavis.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The extent of local invasion in dermatofibrosarcoma protuberans (DFSP) is often clinically difficult to appreciate, and this leads to inadequate resections. We examined the effect of inadequate initial treatment and the efficacy of wide resection.

Methods: We performed a retrospective analysis of the records of 35 patients with DFSP treated at our institution (1985 and 2001). Data were analyzed with Wilcoxon’s ranked sum test and Fisher’s exact test.

Results: Of the 24 patients eligible for analysis, 11 had definitive wide resection after diagnostic excisions elsewhere (primary group), and 13 had recurrent tumors after previous surgical treatment elsewhere (recurrent group). Twenty-three patients were treated with wide resection only, and adjuvant radiation was administered to one patient who had a fibrosarcoma. At a median follow-up of 54 months, patients definitively treated at our institution had a 100% local recurrence–free survival. In comparison to the primary group, recurrent DFSPs were significantly larger and deeper and occurred in the head and neck region. Five cases had bone involvement, and of these, 80% occurred in the recurrent group.

Conclusions: Inadequate initial treatment results in larger, deeper recurrent lesions, but these can be managed by appropriate wide excision. Wide resection of DFSP (whether recurrent or primary) with negative histological margins predicts a superior local recurrence–free survival.

Key Words: Sarcoma • Surgery • Margins • Recurrence


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade mesenchymal tumor that originates in the dermis and accounts for <5% of adult soft tissue sarcomas. This entity was first described by Darrier and Ferrand1 in 1924, but the currently accepted term was coined by Hoffman2 when he reported three cases in 1925. DFSP is characterized by its progressive, locally infiltrative behavior, and if left untreated, these tumors continue to slowly grow, with invasion into surrounding tissue, including neurovascular bundles. Pulmonary and regional lymph node metastases are rare and are usually preceded by multiple local recurrences. Classic DFSP can also progress to the fibrosarcoma-DFSP (FS-DFSP) variant, which is thought to represent dedifferentiation3 and is associated with a significantly higher local recurrence rate and a shorter local recurrence–free survival. The FS-DFSP variant also demonstrates an increased risk for distant metastases.4,5

Most DFSPs occur over the trunk, followed in frequency by the proximal extremities and the head and neck region. The tumor arises as a plaque or a nodule, purple or pink in color in previously healthy skin, or in areas of repeated trauma, vaccination sites, irradiated skin, or scars. It may be misdiagnosed as a keloid.6 The seemingly benign appearance of this tumor can be misleading both to the patient and the physician, resulting in delayed diagnosis and inadequate initial treatment. Despite its distinct microscopic presentation as spindle-shaped tumor cells arranged in a "cartwheel or whirlgig" pattern with fat entrapment, it can represent a diagnostic dilemma for pathologists unfamiliar with this entity.7

Primary therapy for DFSP remains surgical resection. When resections are performed with inadequate margins, the reported local recurrence rate can be as high as 60%.6 A review of 489 cases by Gloster et al.8 reported a local recurrence rate of 18% with use of a surgical margin designated as "wide," or >2 cm. Achieving local control by performing adequate initial resection is important because locally recurrent and neglected lesions have a propensity for deep fascial, muscular, and bone invasion. Moreover, recurrent tumors predisposes to distant metastasis.9 The purpose of our study was to review the University of California, Davis (UCD) experience with DFSP, with the primary focus of analyzing the effect of inadequate initial treatment on the local aggressiveness of recurrent tumors and recurrence-free survival.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
All patients treated for DFSP between 1985 and 2001 were identified in the University of California, Davis Tumor Registry. The medical records were reviewed to obtain information on demographics, tumor characteristics, type of biopsies performed, surgical therapy, pathology reports, and follow-up information. Operative notes and pathology reports from the referring centers were evaluated to determine surgical therapy before referral to UCD.

Definitions
The study population was stratified into two groups: primary and recurrent. The primary group was defined as patients who were referred to UCD for definitive treatment after an initial diagnostic incisional or excisional biopsy. The recurrent group included patients with DFSP in whom tumor had recurred after definitive initial treatment elsewhere or after limited excision yielded an incorrect diagnosis. A microscopically positive margin was defined as tumor present at the inked margin. A complete resection was defined as the absence of any macroscopic residual disease at surgery and negative histological margins on pathologic examination.

Pathology
Pathology reports and operative reports were reviewed to abstract the location (head and neck, trunk, and extremity), anatomical site, tumor size, and depth (superficial or deep) in relation to the investing fascia. Tumor size was defined as the maximum diameter of the tumor determined at operation or during pathologic evaluation. In addition, invasion of bone and adjacent neurovascular structures was recorded. Gross resection margins were obtained from pathology reports by subtracting the maximum tumor diameter from the lesser of the length or width measurements of the resected specimen, documented during pathologic specimen processing.10 These margins were also further verified with the dictated operative report.

Statistical Analysis
Analysis of the two groups in relation to patient, tumor, and treatment factors was conducted by using Wilcoxon’s ranked sum test and Fisher’s exact test. In all statistical analyses, P < .05 was considered significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Of the 35 patients identified from the University of California, Davis Tumor Registry, 24 patients met inclusion criteria. Six patients from the Registry were excluded from analysis because no definitive surgery was ever performed at UCD. Another five patients were definitively treated with Mohs’ micrographic surgery. These cases were excluded from analysis because this study was performed to evaluate the efficacy of wide surgical resection. Because of the small numbers of patients with Mohs’ surgery, a comparison of their outcomes with wide excision was also not statistically possible. Nevertheless, descriptive statistics for patients treated with Mohs’ surgery will be presented. Details of the cohort are listed in Table 1.


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  		TABLE 1. Overall characteristics of the patients with DFSP
 
Our study population consisted of 9 males and 15 females, and their median age at presentation was 36.5 years (range, 10–90 years). In 75% of the patients, the tumor occurred between the ages of 10 and 50 years, and most were white (80%). The lesions were predominantly detected by the patient (87.5%), and the lesion was present for a median duration of 15 months (range, 3–480 months). The median follow up was 4.5 years, and 23 patients were alive without recurrent disease. There was one death, which was unrelated to the DFSP.

There were 11 (46%) patients in the primary group and 13 (54%) patients in the recurrent group (Table 2). None of the patients had clinical evidence of regional lymphatic or distant metastatic disease at presentation. The tumors in the primary group were evenly distributed between the extremities (54%) and an axial location (head, neck, or trunk; 46%). In contrast, tumors in the recurrent group were present mainly in an axial location (92.3%); only one occurred on an extremity (P = .023). When analyzed by individual anatomical sites, recurrent DFSPs were significantly more likely to occur on the head and neck region (recurrent group, 53.8%; primary group, 18%; P = .041). The size and depth of the lesions differed between the two groups. Lesions in the primary group were significantly smaller (3.1 cm; 95% confidence interval [CI], 1.6–4.6 cm) than in the recurrent group (6.14 cm; 95% CI, 3.53–8.87 cm; P = .04). Furthermore, 11 (85%) of 13 recurrent tumors were deep (invading the underlying fascia or lying beneath the fascia), compared with 3 (27%) primary DFSPs (P = .011). Bone involvement was noted only in the recurrent DFSP (4 of 13 cases).


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  		TABLE 2. Comparison of demographic and pathologic characteristics between the primary and the recurrent group
 
In the primary group, all 11 patients had definitive wide local excision at UCD, and in each case the surgeon stated that the gross resection margins were "wide." Subsequent pathologic analysis established the microscopic margins to be tumor free in all cases. In the recurrent group, 17 separate excisions were performed on 13 patients, and 2 of these patients each underwent 3 resections for recurrent lesions. Only 3 of these 17 resections had negative histological margins; this was significantly different from the primary group (P = .00003). When the dictated operative reports were reviewed, in 8 of these 17 resections, the surgeon indicated that the gross resection margin at surgery was "wide," but 5 (62.5%) of these 8 cases had positive microscopic margins. All resections performed at UCD were stated as being "wide" and on pathologic examination had negative microscopic margins (P = .005). Review of pathology reports demonstrated that 38.5% of the cases in the recurrent group were initially misdiagnosed by the outside pathologists as myxoma, fibroma, fibrohistiocytoma, or benign inflammation/fibrous changes. Review of the outside slides by the pathologists at UCD established the correct diagnosis of DFSP at the time of definitive resection. At UCD, all 13 patients with recurrent DFSP underwent wide local resection and had negative histological margins. The gross resection margins used at UCD for DFSP did not vary between tumors in the primary group (2.5 cm; 95% CI, 1.78–3.20 cm) and those in the recurrent group (3.3 cm; 95% CI, 2.37–4.24 cm; P = .244).

Reconstructive soft tissue procedures were used in 12 cases to obtain closure of the wound; a split-thickness skin graft was used in 7 cases, and a pedicled flap was used in 5 cases. However, there was no difference in the need for skin graft or tissue advancement between the primary and recurrent DFSP group. At a median follow-up of 54 months, none of the patients has developed local recurrence after undergoing definitive wide resection at UCD. No patient in this series has developed regional nodal or distant metastasis. No patient has died of disease. One patient (4.1%) in our study was found to have fibrosarcoma concomitant with the DFSP. This patient was treated with adjuvant radiotherapy after wide resection.

Details of the patients treated with Mohs’ resection are listed in Table 3. Lesions in this group were present for a median duration of 36 months (range, 9–300 months). After Mohs’ resection, primary closure was feasible in all cases. The wider resections were primarily performed on the trunk, and the lesions on the face and hand were managed with narrow but negative microscopic margins. After Mohs’ surgery was performed at UCD, none of the patients had developed local recurrence at a median follow-up of 7 years.


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  		TABLE 3. Characteristics of patients with DFSP treated with Moh’s surgery
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
When treating dermatofibrosarcoma protuberans, failure to recognize the existence of clinically undetectable extensions of the tumor within the horizontal plane and to plan surgery accordingly is the cause for inadequate resection and is largely responsible for the reported high local recurrence rates. In this series, we examined the characteristics of DFSP on the basis of the method of presentation, i.e., primary versus recurrent disease. We hypothesized not only that initial inadequate excisions would lead to recurrent lesions, but also that these lesions would behave as locally aggressive tumors.

Our study demonstrated that recurrent lesions display a more aggressive local behavior, because they were significantly deeper and larger. Furthermore, these lesions had an increased incidence of bone involvement. Lindner et al.6 reported that involvement of deep tissue is associated with a greater frequency of recurrence because of the difficulty in achieving complete resection with negative surgical margins. Th experience with head and neck DFSP from Memorial Sloan-Kettering Cancer Center (MSKCC), reported by Stojadinovic et al.,10 also confirmed that deep tumors were significantly more likely to have positive margins. Recurrent lesions in our study were more frequently located on the head/scalp area (P = .041), where it is inherently difficult to obtain wide surgical margins, particularly when the lesions are located near critical facial structures. However, even in these locations, the surgeon should strive to achieve negative margins through wide local excision, because it favorably affects the local recurrence rate.10

The natural history of DFSP is one of slow but progressive growth. In this series, recurrent DFSPs were also shown to be significantly larger than primary lesions. Although the size of the lesion has not been demonstrated to increase the risk of local recurrence,4 it does affect the conduct of the surgical resection and perhaps increases morbidity by necessitating either complex closure or skin grafting. We, however, demonstrated in our study that if an aggressive policy of wide resection is adopted, the need for reconstructive procedures to achieve closure does not differ whether the patient presents with primary or recurrent disease.

Even though recurrent lesions were larger, deeper, and more frequently located in difficult locations, such as the head and neck area, the surgical approach was similar to that used for the primary group. Wide local excision was performed with similar margins (2.5–3.3 cm; P = .244). The principle of wide resection was emphasized almost 50 years ago with the first report on DFSP from MSKCC11 and was reaffirmed in their latest analysis of 159 patients with primary or recurrent DFSP.4 Lindner et al.6 reviewed the literature and advocated that circumferential gross margins from 2.5 to 3.5 cm were adequate to achieve improved local control. The minimum gross resection margin necessary to achieve local control remains undefined, and the rarity of this disease precludes evaluation with a large randomized trial. Most authorities would suggest a margin of 2 to 3 cm of normal tissue from the gross tumor boundary, with a three-dimensional resection that includes skin, subcutaneous tissue, and the underlying investing fascia. In areas with underlying bony structures, often the periosteum and a portion of the bone may also need to be resected to achieve negative deep surgical margins.

However, as important as wide macroscopic resection is, achieving negative microscopic margins is equally critical because it independently influences the local recurrence rate. In our series, when the referring surgeons stated that a wide resection was performed, 62% of patients had positive microscopic margins and consequently experienced a recurrence. In comparison, all our wide resections were achieved with negative microscopic margins to provide a high local recurrence–free survival rate regardless of whether the lesions were primary or recurrent. Analysis of the prospective database of DFSP treated at MSKCC demonstrated that for patients with classic DFSP, 7% with negative microscopic margins and 27% with close or positive microscopic margins experienced recurrence at 5 years.4 The influence of microscopic margins was even more evident for the FS-DFSP variant, for which the respective recurrence rates were 28% and 100%. We had only one patient with the FS-DFSP variant who was treated with adjuvant radiation. Given the aggressive clinical course of these variants, Mentzel et al.3 advocated a more intense therapeutic approach, with use of radiotherapy in select patients.12

The importance of negative microscopic margins is also highlighted by Mohs’ micrographic surgery, an elaborate, time-consuming, and staged surgical procedure that has been reported to achieve high cure rates. This accuracy is achieved by histological and CD34 immunohistochemical examination of serial excisions that facilitates precise mapping of the tumor. This technique may have unique application in children and for locations where radical resection would result in significant functional or cosmetic morbidity. In these situations, Mohs’ surgery has the advantage of precisely tailoring the excision to the extent of the disease rather than using an arbitrary width of excision. In a multi-institutional review of 58 cases of DFSP treated with Mohs’ surgery, an overall local recurrence rate of 2% (0% for primary tumors and 4% for recurrent tumors) was reported.13 In our series, all five cases achieved local control at a median follow-up of 7 years, but with such a small number of cases, definitive comments on the utility of Mohs’ micrographic surgery in comparison to standard wide resection cannot be made.

DFSP is a rare, indolent tumor that can present challenging local problems if initial treatment is inadequate, either because of misdiagnosis or because of failure to perform an appropriate wide resection. Recurrent tumors are significantly more likely than primary DFSP to be deeper and larger and to be located in the difficult head and neck region. However, if a correct diagnosis is established and a gross resection margin of 2.5 to 3.5 cm is used, then a favorable local recurrence–free survival can be achieved.


   FOOTNOTES
 
Inadequate initial treatment of dermatofibrosarcoma protuberans (DFSP) due to misdiagnosis or failure to perform an appropriate wide resection can lead to locally aggressive recurrences. However, both primary and recurrent tumors can be successfully treated with a gross resection margin of 2.5–3.5 cm.

Received for publication March 20, 2003. Accepted for publication July 6, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Darrier J, Ferrand M. Dermatofibromes progressifs et recidivants ou fibrosarcomas de la peau. Ann Dermatol Syphiligr (Paris) 1924; 5: 545–62.
  2. Hoffman E. Uber das knollentreibende fibrosarkom de haut. Dermatol Z 1925; 43: 1–28.
  3. Mentzel T, Beham A, Katenkamp D, Dei Tos AP, Fletcher CD. Fibrosarcomatous ("high-grade") dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance. Am J Surg Pathol 1998; 22: 576–87.[CrossRef][Medline]
  4. Bowne WB, Antonescu CR, Leung DH, et al. Dermatofibrosarcoma protuberans: a clinicopathologic analysis of patients treated and followed at a single institution. Cancer 2000; 88: 2711–20.[CrossRef][Medline]
  5. Diaz-Cascajo C, Weyers W, Rey-Lopez A, Borghi S. Deep dermatofibrosarcoma protuberans: a subcutaneous variant. Histopathology 1998; 32: 552–5.[Medline]
  6. Lindner NJ, Scarborough MT, Powell GJ, Spanier S, Enneking WF. Revision surgery in dermatofibrosarcoma protuberans of the trunk and extremities. Eur J Surg Oncol 1999; 25: 392–7.[Medline]
  7. Taylor HB, Helwig EB. Dermatofibrosarcoma protuberans: a study of 115 cases. Cancer 1962; 15: 717–25.[CrossRef][Medline]
  8. 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 1996; 35: 82–7.[CrossRef][Medline]
  9. Rutgers EJ, Kroon BB, Albus-Lutter CE, Gortzak E. Dermatofibrosarcoma protuberans: treatment and prognosis. Eur J Surg Oncol 1992; 18: 241–8.[Medline]
  10. Stojadinovic A, Karpoff HM, Antonescu CR, et al. Dermatofibrosarcoma protuberans of the head and neck. Ann Surg Oncol 2000; 7: 696–704.[Abstract]
  11. Pack G, Tabah G. Dermatofibrosarcoma protuberans: a report of thirty nine cases. Arch Surg 1951; 62: 391–411.
  12. Lal P, Sharma R, Mohan H, Sekhon MS. Dermatofibrosarcoma protuberans metastasizing to lymph nodes: a case report and review of literature. J Surg Oncol 1999; 72: 178–80.[CrossRef][Medline]
  13. 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 1997; 37: 600–13.[CrossRef][Medline]



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