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Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin
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Journal of Plastic, Reconstructive & Aesthetic Surgery (2015) xx, 1e7
Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin Kyong-Je Woo, Sa Ik Bang, Goo-Hyun Mun, Kap Sung Oh, Jai-Kyong Pyon a, So Young Lim*,a Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Received 8 July 2015; accepted 19 October 2015
KEYWORDS Surgical treatment; Local recurrence; Gross resection margin; Adjuvant radiation; Wide local excision; Frozen biopsy
Summary Background: Controversy exists regarding appropriate surgical treatment for dermatofibrosarcoma protuberans (DFSP). The purpose of this study was to propose treatment recommendations based on long-term outcomes of surgical treatments for DFSP. Methods: A total of 63 patients who underwent surgical resection for primary DFSP were retrospectively reviewed from 1999 to 2011. They were classified into three groups based on the width of the gross resection margins: group I with marginal excision (14 patients); group II with resection margins < 3 cm (21 patients); and group III with resection margins 3 cm (28 patients) (group II and group III had wide local excision). Results: The median follow-up period was 65 months (range 31e190 months). The marginal excision group showed a significantly higher recurrence rate than the wide excision group (35.7% vs. 0%, p < 0.001). Among wide excision groups, group III showed a significantly higher requirement for reconstructive surgery than group II (82.7% vs. 52.4%, p Z 0.011), yet both groups had no recurrence and pathologic margin status was comparable. The accuracy rate of frozen section analyses was 100% for the margin status in the wide excision group. Adjuvant radiation was significantly associated with a reduced recurrence in the marginal excision group (0% vs. 60%, p Z 0.016). Conclusions: Wide local excision with margins of 1.5e2 cm along with frozen biopsy is recommended for DFSP. Either re-excision or adjuvant radiation therapy can serve as a treatment option for patients with positive margins. ª 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwonro, Gangnam-gu, Seoul 135-710, South Korea. Tel.: þ82 2 3410 2239; fax: þ82 2 3410 0036. E-mail address: [email protected] (S.Y. Lim). a Jai-Kyong Pyon and So Young Lim contributed equally as corresponding authors. http://dx.doi.org/10.1016/j.bjps.2015.10.027 1748-6815/ª 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Woo K-J, et al., Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin, Journal of Plastic, Reconstructive & Aesthetic Surgery (2015), http://dx.doi.org/10.1016/ j.bjps.2015.10.027
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Introduction Dermatofibrosarcoma protuberans (DFSP) is a rare painless tumor of the skin with an incidence of 0.8e5 cases per 1 million people annually.1 Approximately 85e90% of all DFSPs are low-grade lesions, and the remaining small proportion is associated with a high-grade fibrosarcomatous component.2 Immunohistochemical staining for CD34 is often used for differential diagnosis, because it is positive for DFSP, but negative for dermatofibroma. Tayler et al. first described the histological characteristics of DFSP as spindle-shaped tumor cells invading local tissue by direct extension.3 Local recurrence is frequent after surgical excision, because microscopic tumor margins usually extend beyond the gross margins. Despite frequent local recurrence, DFSP rarely metastasizes unless it undergoes fibrosarcomatous change.4 The probability of regional or distant metastasis is <5% and is frequently preceded by multiple local recurrences. Because recurrence is closely related to adequate surgical margins, obtaining a negative margin through surgical excision is the primary goal of DFSP treatment.5,6 In this regard, wide local excision with margins of at least 3e4 cm has long been recommended as the standard treatment for DFSP.1,7e9 However, recent studies have demonstrated that a good local control could be achieved with narrow resection margins.10e12 The authors have clinically experienced that margins 3 cm in wide local excision often necessitated reconstructive surgery, because even a 1-cm-sized tumor caused a defect of >7 cm. Therefore, it can be of special concern to reconstructive surgeons whether wide excision with gross resection margins of at least 3 cm improved treatment outcomes. Controversy also exists on the role of radiation therapy as an adjuvant therapy. While several single-institution series have reported good local control after adjuvant radiotherapy, these were limited by heterogeneous surgical modalities, which made the direct comparison impossible.13e16 Although frozen sections play a vital role in the evaluation of margins of basal and squamous cell carcinomas, the role of frozen sections in evaluation of softtissue tumors is controversial.17 The purpose of this study was to propose treatment recommendations based on the long-term outcomes of surgical treatments in 63 DFSP patients and a literature review. Treatment outcomes were reviewed focusing on the effect of surgical margins on local recurrence, role of adjuvant radiation therapy, and intraoperative frozen section assessment.
K.-J. Woo et al. who were diagnosed with DFSP by pathologic analysis were also included in this study. Sex, age, tumor location, tumor size, width of gross resection margin, intraoperative frozen biopsy, pathologic analysis, adjuvant radiotherapy, followup period, and recurrence were analyzed. Patients with a follow-up period of <2 years were not included in this study because of the risk of late recurrence.1 Patients were classified into three groups based on the width of the gross resection margin. Group I consisted of patients with marginal excision of the tumor. Patients who received wide local excision were further divided by the width of the gross resection margin into group II and group III (group II: resection margin <3 cm; group III: resection margin 3 cm). The gross resection margin was defined as the closest gross margin as measured by the surgeon at the time of resection.
Surgical treatment Wide local excision was the mainstay of surgical treatment for the patients in this study. The width of the gross resection margin was determined by the surgeon based on tumor location and surgeon’s experience and preferences. The incision line was marked on the normal skin to obtain the planned distance from the tumor margin. Dissection proceeded vertically through subcutaneous tissue until the investing fascia (deep fascia) was exposed. The investing fascia was resected together with the tumor. The specimen was sent to a pathological laboratory for intraoperative frozen section assessment. Four lateral margins (12, 3, 6, and 9 O’clock) and one deep margin were evaluated. Further resection was performed if a positive margin was reported. Primary closure or reconstructive surgery was performed once a negative resection margin was confirmed by frozen biopsy. Frozen biopsy was not undertaken in some cases based on the surgeon’s clinical decision or when frozen section analysis was not available. CD34 staining was performed to distinguish DFSP from other soft-tissue tumors. Except for the width of the peripheral resection margin, patients in groups II and III received the same surgical treatment. Group I patients underwent marginal excision that did not include normal skin or soft tissue in the resected specimen. Marginal excision was planned based on cosmetic or functional concerns or when the excision was for the diagnostic confirmation of the tumor. The patients consulted with a radiation oncologist about adjuvant radiation. Some patients preferred only follow-up to radiation therapy. The dose of radiation was 200 cGy per fraction, 30 fractioned, with a total dose of 60 Gy.
Material and methods Statistical analysis Data collection The institutional review board of authorized institution approved this retrospective study (study number: 2014-09137). A total of 65 cases were retrospectively reviewed in 63 patients with DFSP who underwent surgical resection from 1999 to 2011 (one patient underwent resection thrice because of recurrences). Patients with primary tumor (except the two cases of recurrent surgery in one patient)
Statistical analysis was performed using SAS version 9.3 (SAS Institute Inc, Cary, NC, USA). The primary outcomes were recurrence and the rate at which patients needed reconstructive surgery at the time of the excision. Probable confounding factors, such as tumor size, follow-up, and tumor location (rate of head and neck tumor), were also analyzed to identify between-group differences. Fisher’s exact test and the KruskaleWallis test were used to obtain
Please cite this article in press as: Woo K-J, et al., Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin, Journal of Plastic, Reconstructive & Aesthetic Surgery (2015), http://dx.doi.org/10.1016/ j.bjps.2015.10.027
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Surgical treatment for dermatofibrosarcoma protuberans categorical and numerical data, respectively. P values were corrected by Bonferroni’s method in the case of multiple testing. Samples were statistically significant when p < 0.05.
Results Patient demographics A total of 63 patients were included in this study, including one patient in group I who experienced recurrence twice and underwent surgical excision 18 and 12 months postoperatively. The mean age of all patients was 38.8 years, with a peak incidence in their 30s. The patient group included 33 (52.4%) males and 30 (47.6%) females. The tumor was most commonly on the trunk (n Z 28, 44.4%) followed by the lower extremities (n Z 16, 25.4%) and the head and neck (n Z 11, 17.5%) (Table 1). CD34 staining was performed in 30 patients and fount to be positive in 93.3% (28 patients).
Treatment outcomes The median follow-up period was 65 months (range 31e190 months) (Table 2). The marginal excision group had a recurrence rate of 35.7% (5 of 14), while groups II and III
Table 1
Patient demographics.
Sex Female Male Total Age (years) <20 21e30 31e40 41e50 51e60 61e70 >71 Location of the tumor Head and neck Trunk Chest, clavicle Abdomen Back Upper extremity Shoulder Arm and hand Lower extremity Groin Thigh Lower leg and foot CD34 staining Total Positive
Frequency
Percentage
30 33 63
47.6 52.4 100
4 15 20 12 6 5 1
6.4 23.8 31.8 19 9.5 7.9 1.6
11 28 10 7 11 8 5 3 16 3 6 7
17.5 44.4
30 28
12.7
25.4
93.3
3 showed no recurrence during the follow-up period. The marginal excision group had a significantly higher (p < 0.001, one-sided) recurrence rate than the wide local excision group. Tumor size, rate of head and neck tumors, and follow-up period did not differ among the three groups. The median sizes of the tumor were 9.75 (interquartile range 3e25), 4 (2.1e6.25), and 6.75 cm2 (interquartile range 2.25e17 cm2) for groups I, II, and III, respectively (p Z 0.186). The mean gross resection margins of groups II and III were 1.86 (range 0.5e2.5, SD: 0.73) and 3.68 cm (range 3.0e5.0 cm, SD: 0.76), respectively. Intraoperative frozen section analysis was performed in 35 out of 49 patients in the wide excision group (Table 3). Clear lateral margins were achieved at initial resection in 93.3% (14 out of 15 patients) of group II patients and 95% (19 out of 20 patients) of group III patients. Deep margins were positive for tumor cells in three patients at initial excision. Further excision at the location of positive margins resulted in clear margins of frozen biopsy in all patients (five patients) with positive frozen margins. The accuracy rate of frozen section analysis was 100% compared with the permanent sections. In the wide excision group, the rates of clear permanent margins in no-frozen biopsy group and frozen biopsy group were 85.7% (12 out of 14 patients) and 100% (35 out of 35 patients), respectively. Although it was not statistically significant, the no-frozen biopsy was associated with a trend toward increased odds of positive permanent margins (odds Z 1.167, 95% CI: 0.942e1.445, p Z 0.077, two-sided). Of the 10 patients with data for final pathologic margin in group I, seven patients (70%) had positive margins (Table 3). The rates of negative margin in the final pathologic results for groups I, II, and III were 30% (3 out of 10 patients), 95.2% (20 out of 21), and 96.4% (27 out of 28 patients), respectively (p Z 0.670, one-sided). All patients with negative margins had no recurrences. However, the recurrence rate in patients with positive margins after marginal excision was 42.8% (three out of seven patients). One patient each from groups II and III had focal positive lateral margins on permanent section analysis. The gross resection margins of the patients with positive margins were 0.8 and 4 cm, and intraoperative frozen biopsy was not performed for both of them. The two patients with positive margins declined further treatment, and were followed up for 70 and 124 months, respectively, and no recurrence was found. Radiation therapy was provided to six patients in group I (Table 4). Two patients with positive margin and one recurrent patient were included in this patient group. However, none of them experienced recurrence. On the contrary, recurrence rate of nonradiation group was 60% (6 out of 10 patients), and one patient recurred twice. One patient in group I underwent marginal excision thrice because of recurrence at 18 and 12 months postoperatively. The patient received adjuvant radiotherapy after the third surgery, and did not experience recurrence for over 14 years. Adjuvant radiotherapy was significantly associated with a reduced recurrence rate (p Z 0.016, one-sided). There was no serious complication from radiation therapy. The need for reconstructive surgeries such as skin graft or flap surgery was significantly higher in group III than group II (82.7% vs. 52.4%, p Z 0.011, one-sided).
Please cite this article in press as: Woo K-J, et al., Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin, Journal of Plastic, Reconstructive & Aesthetic Surgery (2015), http://dx.doi.org/10.1016/ j.bjps.2015.10.027
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K.-J. Woo et al. Table 2
Outcomes of treatment.
Number of patients Recurrence, n (%) Median size of tumor, cm2 (IQR) Head and neck location, n (%) Median follow-up periods, months (IQR) Needs for reconstructive surgery, n (%)
Total
Group I
Group II WLE (<3 cm) Group III WLE (3 cm) P value
63 5 (7.9) 6 (2.2e13.7) 11 (17.5) 65 (47e108) 0
14 5 (35.7) 9.7 (3e25) 4 (28.6) 75 (60e122) 1 (7.1)
21 0 4 (2.1e6.2) 5 (23.8) 58 (45e84) 11 (52.4)
28 0 6.7 (2.2e17) 2 (7.1) 64.5 (46.5e103) 24 (82.7)
<0.001a 0.186b 0.140c 0.233b 0.011d
IQR, interquartile range; WLE, wide local excision. a Group I vs. (group II þ group III), one-sided, Fisher’s exact test. b KruskaleWallis test. c Two-sided, Fisher’s exact test. d Group II vs. group III, one-sided, Fisher’s exact test.
Discussion Surgical treatment modalities for DFSP In this study, marginal excision showed a high recurrence rate (35.7%). The rate of positive final pathologic margin was as high as 70% (7 out of 10). On the contrary, groups II and III showed no recurrence during a median follow-up of 60 months (range 31e190 months). Tumor size, rate of head and neck tumors, and follow-up period are potential confounders that can influence the recurrence rate. These variables did not differ between the three groups. In addition, Kimmel et al. reported that preoperative tumor size did not correlate well with true tumor extent.7 Our current experience provides supporting evidence that wide local excision should be a first-line surgical modality for DFSP. There has been no consensus as to what gross margin of excision constitutes proper surgical management. Wide local excision with gross resection margins of 3 cm has Table 3
Table 4 Effects of adjuvant radiotherapy on recurrences in marginal excision. No Radiotherapy Total P radiotherapy value
Microscopic margin status and recurrences. Group Group Group P value I II III
Total number of patients Intraoperative frozen biopsy, n Negative lateral margins at initial resection, n (%) Negative deep margins at initial resection, n (%) Negative permanent margins, n (%) Permanent margin status described, n Negative permanent margins, n (%) Recurrence in patients with negative margins, n (%) Recurrence in patients with positive margins, n (%) a
long been recommended as the standard treatment for DFSP.1,8 A meta-analysis of 98 patients found that a standard wide excision margin of 4 cm was predicted to provide a tumor clearance rate of 95%.7 A 5 cm of peripheral excision margin was performed in certain studies for wide local excision.18 However, a multidisciplinary approach and advances in pathologic technique have led to a recent reduction in recommended gross resection margins for DFSP (Table 5).1,7e12,18,19 Recent studies reported very low or no local recurrences after excision with <3-cm margins.11,12 In 1995, Parker et al. performed Mohs surgery to measure the subclinical extent of tumor and determine appropriate surgical margins and found that a 2.5-cm surgical margin removed all the tumors.19 Mohs surgery is an effective surgical modality for the treatment of DFSP.20e24 Mohs surgery minimizes surgical
14 0
21 15
28 20
e
14 (93.3) 13 (86.6) 15 (100) 21
19 (95) >0.999*
e e 10
19 (95) 20 (100) 28
3 (30) 20 27 0.679a (95.2) (96.4) 0 0 0
3 0 (42.8)
0
Two-sided, Fisher’s exact test between groups II and III.
Total cases, n Recurrence among total cases, n (%) Cases evaluated permanent margins, n Positive margins, n Negative margins, n Recurrence among positive margins, n (%) Recurrence among negative margins, n (%)
10 6 (60.0)
6 0
16a 6 0.016b (37.5)
6
4
10
5
2
7
1
2
3
3 (60.0)
0
3 (42.8)
0
0
0
a
Total surgical cases were 16 in 14 patients, a patient in group I got surgical treatment thrice because of recurrences. Adjuvant radiation was performed after the third surgery. b One-sided, Fisher’s exact test.
Please cite this article in press as: Woo K-J, et al., Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin, Journal of Plastic, Reconstructive & Aesthetic Surgery (2015), http://dx.doi.org/10.1016/ j.bjps.2015.10.027
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Surgical treatment for dermatofibrosarcoma protuberans Table 5
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References regarding gross resection margins of DFSP.
Authors/Ref. No.
Year
No. of cases
Gross margins, mean
Follow-up period, mean
Recurrences (%)
Recommended gross resection margins for wide local excision
Kokkinos10 Hersant11 Farma12 Parker19
2014 2013 2010 1995
20 66 204 20
20 mm or 30 mm 18 mm (10e30 mm) 20 mm (5e30 mm) Mohs (5e25 mm)
5.6 years 30 months 64 months NS
0 0 1 NS
Kimmel7
2007
98
Systematic review
NS
NS
Monnier1
2006 2004 1997
Roses9
1986
<3 cm 3e5 cm 3 cm 5 cm 5 cm <2 cm 2 cm 3 cm
9.6 years
Chang8 Arnaud18
32 30 60 66 primary 41 recurred 50, total
47 7 16.70 0 4.80 41 24 20
20 mm 10e30 mm 10e20 mm 2.5-cm margin removed all the tumors 4-cm margins provided a tumor clearance rate of 95% 3 cm
margins, preserving cosmetically and functionally vital tissues.25 It is most useful in treating head and neck tumors.21 Systematic reviews and retrospective studies reported a lower rate of recurrence with Mohs micrographic surgery than wide local excision.21,24,26,27 On the contrary, it requires multiple excisions and takes more time than wide local excision.28 In addition, a specially trained surgeon and dermatopathologist are necessary for Mohs surgery.17 It is unclear whether Mohs surgery is superior to wide local excision.10,28 The choice between wide local excision and Mohs surgery should be based on tumor characteristics and institutional expertise in these modalities.28
Frozen biopsy and gross resection margin in wide local excision Frozen sections of skin are an effective tool for margin assessment of primary epithelial malignancies of the skin.17 The authors used intraoperative frozen section analysis to reduce the rate of incomplete excision. Further resection was performed in five patients and clear margins could be achieved. This adjunctive method could reduce peripheral excision margins without increasing the possibility of incomplete excision. In surgical resections for DFSP, the deep fascia (nonscalp) or periosteum (scalp) should be resected to remove all the tumors.19 Our case series showed that tumor cells could spread deeper than the deep fascia. Although DFSP is not an aggressive tumor, a deep subcutaneous punch or incisional biopsy for the diagnosis could facilitate vertical spread of the tumor cells. While controversy exists regarding the use of frozen sections in DFSP, frozen biopsy can be an effective way to obtain negative margins, particularly at the deep surface of the DFSP.29 In this study, frozen section assessment could permit reconstructive surgery concurrently with excision. It usually takes <30 min to analyze the frozen section.30 The
59 months 61 months 7.3 years
3 cm 5 cm 3 cm
accuracy of frozen section analysis varies from center to center, but there have been attempts to improve the quality of assessment by using high-quality, completely faced section.17,31 If the frozen biopsy is unavailable, magnetic resonance (MR) imaging can be useful for preoperative evaluation of the depth of infiltration and extent of the tumor.32,33 Permanent pathologic margins were comparable between groups II and III. One patient from each group had a positive lateral margin in the final report. The patient in group III underwent wide excision with a 4-cm resection margin following tissue expander surgery around the tumor for reconstruction. It was assumed that the expansion of the skin around the tumor could have influenced the spread of the tumor. Popov et al. analyzed the differences between gross and histological margins and found that a mean difference of 1.5 cm existed.34 In our case series, four patients in group II had resection margins <1 cm. Although they did not experience recurrence during the follow-up period, a resection margin <1 cm may lead to an increased risk of positive margins during initial excision. This study of long-term follow-up >5 years demonstrated that margins >3 cm for wide local excision did not vary in pathologic status or rate of recurrence, although those patients did have an increased need for reconstructive surgery. Wide local excision with margins <3 cm would be appropriate for initial excision. On the contrary, a <1cm margin may increase the rate of recurrence considering the difference between gross and histologic margins. Therefore, the authors recommend a gross resection margin of 1.5e2 cm with frozen biopsy for initial wide local excision.
Adjuvant radiation therapy Despite the inclusion of two patients with positive margin and one recurrent patient, no recurrence was found in
Please cite this article in press as: Woo K-J, et al., Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin, Journal of Plastic, Reconstructive & Aesthetic Surgery (2015), http://dx.doi.org/10.1016/ j.bjps.2015.10.027
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patients who underwent adjuvant radiation following marginal excision (Table 4). On the contrary, 60% (6 out of 10 patients) without adjuvant radiation following marginal excision had recurrences (p Z 0.016, one-sided). This result suggests that adjuvant radiation therapy can serve as a treatment option for patients with positive margins, particularly when re-excision will cause severe cosmetic or functional problems. The first report on radiation therapy for DFSP was provided by Rinck et al., in 1982.35 Many studies have reported the positive role of adjuvant radiation therapy for DFSP.2,15,16,36 In the largest study, 53 patients received adjuvant radiation therapy with a local control rate of 93% at 10 years.37 However, none of these was a comparative study and the surgical modalities were heterogeneous. Although the number of patients was small, the authors performed direct comparison in group I patients who underwent the same surgical modality of marginal excision.
Treatment recommendations Treatment recommendations for DFSP were proposed in Figure 1. Initial wide local excision has a definite role in the treatment of DFSP, because inadequate initial treatment can result in larger and deeper recurrent lesions.38 Wide local excision should be considered if the initial treatment was marginal excision. A resection margin of 1.5e2 cm with intraoperative frozen section analysis is reasonable for an initial wide local excision. If the intraoperative frozen biopsy is positive, further resection with margins approximately 1 cm can be performed at the positive margin. The specimen is subjected to final pathologic evaluation, and the defect is closed primarily or covered by reconstructive surgery. Either re-excision or adjuvant radiation therapy can be a treatment option if the final pathologic margin is positive for tumor cells. Recurrent disease can also be managed by appropriate wide excision.38 The potential limitations of this study are as follows: surgeries were not performed by a single surgeon and the recurrence rate in groups II and III could not be compared statistically, because no recurrence was found. In spite of these limitations, this study is the first of its kind to compare long-term outcomes of three different surgical treatment methods. This study suggests that gross resection margins >3 cm had no benefits regarding treatment outcomes. In addition, the current study demonstrated the positive role of intraoperative frozen section analysis and adjuvant radiation therapy, and provided treatment recommendations for DFSP.
Conclusions Treatment recommendations for DFSP were proposed based on the long-term treatment outcomes and a literature review. A resection margin of 1.5e2 cm together with frozen biopsy is sufficient for an initial wide local excision. As DFSP is a radiosensitive disease, either re-excision or adjuvant radiation therapy can serve as a treatment option for patients with positive margins.
Figure 1 Treatment recommendations brosarcoma protuberans (DFSP).
for
dermatofi-
Conflicts of interest statement This study has no source of any financial or material support. There are no potential conflicts of interest for this study.
References 1. Monnier D, Vidal C, Martin L, et al. Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002. J Eur Acad Dermatol Venereol 2006;20:1237e42. 2. Mendenhall WM, Zlotecki RA, Scarborough MT. Dermatofibrosarcoma protuberans. Cancer 2004;101:2503e8. 3. Taylor HB, Helwig EB. Dermatofibrosarcoma protuberans. A study of 115 cases. Cancer 1962;15:717e25. 4. Minter RM, Reith JD, Hochwald SN. Metastatic potential of dermatofibrosarcoma protuberans with fibrosarcomatous change. J Surg Oncol 2003;82:201e8.
Please cite this article in press as: Woo K-J, et al., Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin, Journal of Plastic, Reconstructive & Aesthetic Surgery (2015), http://dx.doi.org/10.1016/ j.bjps.2015.10.027
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Surgical treatment for dermatofibrosarcoma protuberans 5. Heuvel ST, Suurmeijer A, Pras E, Van Ginkel RJ, Hoekstra HJ. Dermatofibrosarcoma protuberans: recurrence is related to the adequacy of surgical margins. Eur J Surg Oncol 2010;36:89e94. 6. Bowne WB, Antonescu CR, Leung DH, et al. Dermatofibrosarcoma protuberans: a clinicopathologic analysis of patients treated and followed at a single institution. Cancer 2000;88:2711e20. 7. Kimmel Z, Ratner D, Kim JY, Wayne JD, Rademaker AW, Alam M. Peripheral excision margins for dermatofibrosarcoma protuberans: a meta-analysis of spatial data. Ann Surg Oncol 2007;14:2113e20. 8. Chang CK, Jacobs IA, Salti GI. Outcomes of surgery for dermatofibrosarcoma protuberans. Eur J Surg Oncol 2004;30: 341e5. 9. Roses DF, Valensi Q, LaTrenta G, Harris MN. Surgical treatment of dermatofibrosarcoma protuberans. Surg Gynecol Obstet 1986;162:449e52. 10. Kokkinos C, Sorkin T, Powell B. To Mohs or not to Mohs. J Plast Reconstr Aesthet Surg 2014;67:23e6. 11. Hersant B, May P, Battistella M, Pages C, Lebbe C, Revol M. Reducing surgical margins in dermatofibrosarcoma protuberans using the pathological analysis technique ’vertical modified technique’: a 5-year experience. J Plast Reconstr Aesthet Surg 2013;66:617e22. 12. Farma JM, Ammori JB, Zager JS, et al. Dermatofibrosarcoma protuberans: how wide should we resect? Ann Surg Oncol 2010; 17:2112e8. 13. Dagan R, Morris CG, Zlotecki RA, Scarborough MT, Mendenhall WM. Radiotherapy in the treatment of dermatofibrosarcoma protuberans. Am J Clin Oncol 2005;28:537e9. 14. Sun LM, Wang CJ, Huang CC, et al. Dermatofibrosarcoma protuberans: treatment results of 35 cases. Radiother Oncol 2000; 57:175e81. 15. Ballo MT, Zagars GK, Pisters P, Pollack A. The role of radiation therapy in the management of dermatofibrosarcoma protuberans. Int J Radiat Oncol Biol Phys 1998;40:823e7. 16. Suit H, Spiro I, Mankin HJ, Efird J, Rosenberg AE. Radiation in management of patients with dermatofibrosarcoma protuberans. J Clin Oncol 1996;14:2365e9. 17. Smith-Zagone MJ, Schwartz MR. Frozen section of skin specimens. Arch Pathol Lab Med 2005;129:1536e43. 18. Arnaud EJ, Perrault M, Revol M, Servant JM, Banzet P. Surgical treatment of dermatofibrosarcoma protuberans. Plast Reconstr Surg 1997;100:884e95. 19. Parker TL, Zitelli JA. Surgical margins for excision of dermatofibrosarcoma protuberans. J Am Acad Dermatol 1995;32: 233e6. 20. Loghdey MS, Varma S, Rajpara SM, Al-Rawi H, Perks G, Perkins W. Mohs micrographic surgery for dermatofibrosarcoma protuberans (DFSP): a single-centre series of 76 patients treated by frozen-section Mohs micrographic surgery with a review of the literature. J Plast Reconstr Aesthet Surg 2014; 67:1315e21. 21. Paradisi A, Abeni D, Rusciani A, et al. Dermatofibrosarcoma protuberans: wide local excision vs. Mohs micrographic surgery. Cancer Treat Rev 2008;34:728e36. 22. Nelson RA, Arlette JP. Mohs micrographic surgery and dermatofibrosarcoma protuberans: a multidisciplinary approach in 44 patients. Ann Plast Surg 2008;60:667e72.
7 23. Snow SN, Gordon EM, Larson PO, Bagheri MM, Bentz ML, Sable DB. Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature. Cancer 2004;101: 28e38. 24. Gloster Jr HM, 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;35:82e7. 25. Dawes KW, Hanke CW. Dermatofibrosarcoma protuberans treated with Mohs micrographic surgery: cure rates and surgical margins. Dermatol Surg 1996;22:530e4. 26. Bogucki B, Neuhaus I, Hurst EA. Dermatofibrosarcoma protuberans: a review of the literature. Dermatol Surg 2012;38: 537e51. 27. Foroozan M, Sei JF, Amini M, Beauchet A, Saiag P. Efficacy of Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans: systematic review. Arch Dermatol 2012;148:1055e63. 28. Meguerditchian AN, Wang J, Lema B, Kraybill WG, Zeitouni NC, Kane 3rd JM. Wide excision or Mohs micrographic surgery for the treatment of primary dermatofibrosarcoma protuberans. Am J Clin Oncol 2010;33:300e3. 29. Massey RA, Tok J, Strippoli BA, Szabolcs MJ, Silvers DN, Eliezri YD. A comparison of frozen and paraffin sections in dermatofibrosarcoma protuberans. Dermatol Surg 1998;24: 995e8. 30. Horn LC, Wagner S. Frozen section analysis of vulvectomy specimens: results of a 5-year study period. Int J Gynecol Pathol 2010;29:165e72. http: //dx.doi.org/10.1097/PGP.0b013e3181b8e5d4. 31. Manstein ME, Manstein CH, Smith R. How accurate is frozen section for skin cancers? Ann Plast Surg 2003;50:607e9. 32. Serra-Guillen C, Sanmartin O, Llombart B, et al. Correlation between preoperative magnetic resonance imaging and surgical margins with modified Mohs for dermatofibrosarcoma protuberans. Dermatol Surg 2011;37:1638e45. 33. Torreggiani WC, Al-Ismail K, Munk PL, Nicolaou S, O’Connell JX, Knowling MA. Dermatofibrosarcoma protuberans: MR imaging features. AJR Am J Roentgenol 2002;178:989e93. 34. Popov P, Bohling T, Asko-Seljavaara S, Tukiainen E. Microscopic margins and results of surgery for dermatofibrosarcoma protuberans. Plast Reconstr Surg 2007;119:1779e84. 35. Rinck PA, Habermalz HJ, Lobeck H. Effective radiotherapy in one case of dermatofibrosarcoma protuberans. Strahlentherapie 1982;158:681e5. 36. Haas RL, Keus RB, Loftus BM, Rutgers EJ, van Coevorden F, Bartelink H. The role of radiotherapy in the local management of dermatofibrosarcoma protuberans. Soft Tissue Tumours Working Group. Eur J Cancer 1997;33:1055e60. 37. Castle KO, Guadagnolo BA, Tsai CJ, Feig BW, Zagars GK. Dermatofibrosarcoma protuberans: long-term outcomes of 53 patients treated with conservative surgery and radiation therapy. Int J Radiat Oncol Biol Phys 2013;86:585e90. 38. Khatri VP, Galante JM, Bold RJ, Schneider PD, Ramsamooj R, Goodnight Jr JE. Dermatofibrosarcoma protuberans: reappraisal of wide local excision and impact of inadequate initial treatment. Ann Surg Oncol 2003;10:1118e22.
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Journal of Plastic, Reconstructive & Aesthetic Surgery (2015) xx, 1e7
Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin Kyong-Je Woo, Sa Ik Bang, Goo-Hyun Mun, Kap Sung Oh, Jai-Kyong Pyon a, So Young Lim*,a Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Received 8 July 2015; accepted 19 October 2015
KEYWORDS Surgical treatment; Local recurrence; Gross resection margin; Adjuvant radiation; Wide local excision; Frozen biopsy
Summary Background: Controversy exists regarding appropriate surgical treatment for dermatofibrosarcoma protuberans (DFSP). The purpose of this study was to propose treatment recommendations based on long-term outcomes of surgical treatments for DFSP. Methods: A total of 63 patients who underwent surgical resection for primary DFSP were retrospectively reviewed from 1999 to 2011. They were classified into three groups based on the width of the gross resection margins: group I with marginal excision (14 patients); group II with resection margins < 3 cm (21 patients); and group III with resection margins 3 cm (28 patients) (group II and group III had wide local excision). Results: The median follow-up period was 65 months (range 31e190 months). The marginal excision group showed a significantly higher recurrence rate than the wide excision group (35.7% vs. 0%, p < 0.001). Among wide excision groups, group III showed a significantly higher requirement for reconstructive surgery than group II (82.7% vs. 52.4%, p Z 0.011), yet both groups had no recurrence and pathologic margin status was comparable. The accuracy rate of frozen section analyses was 100% for the margin status in the wide excision group. Adjuvant radiation was significantly associated with a reduced recurrence in the marginal excision group (0% vs. 60%, p Z 0.016). Conclusions: Wide local excision with margins of 1.5e2 cm along with frozen biopsy is recommended for DFSP. Either re-excision or adjuvant radiation therapy can serve as a treatment option for patients with positive margins. ª 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwonro, Gangnam-gu, Seoul 135-710, South Korea. Tel.: þ82 2 3410 2239; fax: þ82 2 3410 0036. E-mail address: [email protected] (S.Y. Lim). a Jai-Kyong Pyon and So Young Lim contributed equally as corresponding authors. http://dx.doi.org/10.1016/j.bjps.2015.10.027 1748-6815/ª 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
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Introduction Dermatofibrosarcoma protuberans (DFSP) is a rare painless tumor of the skin with an incidence of 0.8e5 cases per 1 million people annually.1 Approximately 85e90% of all DFSPs are low-grade lesions, and the remaining small proportion is associated with a high-grade fibrosarcomatous component.2 Immunohistochemical staining for CD34 is often used for differential diagnosis, because it is positive for DFSP, but negative for dermatofibroma. Tayler et al. first described the histological characteristics of DFSP as spindle-shaped tumor cells invading local tissue by direct extension.3 Local recurrence is frequent after surgical excision, because microscopic tumor margins usually extend beyond the gross margins. Despite frequent local recurrence, DFSP rarely metastasizes unless it undergoes fibrosarcomatous change.4 The probability of regional or distant metastasis is <5% and is frequently preceded by multiple local recurrences. Because recurrence is closely related to adequate surgical margins, obtaining a negative margin through surgical excision is the primary goal of DFSP treatment.5,6 In this regard, wide local excision with margins of at least 3e4 cm has long been recommended as the standard treatment for DFSP.1,7e9 However, recent studies have demonstrated that a good local control could be achieved with narrow resection margins.10e12 The authors have clinically experienced that margins 3 cm in wide local excision often necessitated reconstructive surgery, because even a 1-cm-sized tumor caused a defect of >7 cm. Therefore, it can be of special concern to reconstructive surgeons whether wide excision with gross resection margins of at least 3 cm improved treatment outcomes. Controversy also exists on the role of radiation therapy as an adjuvant therapy. While several single-institution series have reported good local control after adjuvant radiotherapy, these were limited by heterogeneous surgical modalities, which made the direct comparison impossible.13e16 Although frozen sections play a vital role in the evaluation of margins of basal and squamous cell carcinomas, the role of frozen sections in evaluation of softtissue tumors is controversial.17 The purpose of this study was to propose treatment recommendations based on the long-term outcomes of surgical treatments in 63 DFSP patients and a literature review. Treatment outcomes were reviewed focusing on the effect of surgical margins on local recurrence, role of adjuvant radiation therapy, and intraoperative frozen section assessment.
K.-J. Woo et al. who were diagnosed with DFSP by pathologic analysis were also included in this study. Sex, age, tumor location, tumor size, width of gross resection margin, intraoperative frozen biopsy, pathologic analysis, adjuvant radiotherapy, followup period, and recurrence were analyzed. Patients with a follow-up period of <2 years were not included in this study because of the risk of late recurrence.1 Patients were classified into three groups based on the width of the gross resection margin. Group I consisted of patients with marginal excision of the tumor. Patients who received wide local excision were further divided by the width of the gross resection margin into group II and group III (group II: resection margin <3 cm; group III: resection margin 3 cm). The gross resection margin was defined as the closest gross margin as measured by the surgeon at the time of resection.
Surgical treatment Wide local excision was the mainstay of surgical treatment for the patients in this study. The width of the gross resection margin was determined by the surgeon based on tumor location and surgeon’s experience and preferences. The incision line was marked on the normal skin to obtain the planned distance from the tumor margin. Dissection proceeded vertically through subcutaneous tissue until the investing fascia (deep fascia) was exposed. The investing fascia was resected together with the tumor. The specimen was sent to a pathological laboratory for intraoperative frozen section assessment. Four lateral margins (12, 3, 6, and 9 O’clock) and one deep margin were evaluated. Further resection was performed if a positive margin was reported. Primary closure or reconstructive surgery was performed once a negative resection margin was confirmed by frozen biopsy. Frozen biopsy was not undertaken in some cases based on the surgeon’s clinical decision or when frozen section analysis was not available. CD34 staining was performed to distinguish DFSP from other soft-tissue tumors. Except for the width of the peripheral resection margin, patients in groups II and III received the same surgical treatment. Group I patients underwent marginal excision that did not include normal skin or soft tissue in the resected specimen. Marginal excision was planned based on cosmetic or functional concerns or when the excision was for the diagnostic confirmation of the tumor. The patients consulted with a radiation oncologist about adjuvant radiation. Some patients preferred only follow-up to radiation therapy. The dose of radiation was 200 cGy per fraction, 30 fractioned, with a total dose of 60 Gy.
Material and methods Statistical analysis Data collection The institutional review board of authorized institution approved this retrospective study (study number: 2014-09137). A total of 65 cases were retrospectively reviewed in 63 patients with DFSP who underwent surgical resection from 1999 to 2011 (one patient underwent resection thrice because of recurrences). Patients with primary tumor (except the two cases of recurrent surgery in one patient)
Statistical analysis was performed using SAS version 9.3 (SAS Institute Inc, Cary, NC, USA). The primary outcomes were recurrence and the rate at which patients needed reconstructive surgery at the time of the excision. Probable confounding factors, such as tumor size, follow-up, and tumor location (rate of head and neck tumor), were also analyzed to identify between-group differences. Fisher’s exact test and the KruskaleWallis test were used to obtain
Please cite this article in press as: Woo K-J, et al., Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin, Journal of Plastic, Reconstructive & Aesthetic Surgery (2015), http://dx.doi.org/10.1016/ j.bjps.2015.10.027
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Surgical treatment for dermatofibrosarcoma protuberans categorical and numerical data, respectively. P values were corrected by Bonferroni’s method in the case of multiple testing. Samples were statistically significant when p < 0.05.
Results Patient demographics A total of 63 patients were included in this study, including one patient in group I who experienced recurrence twice and underwent surgical excision 18 and 12 months postoperatively. The mean age of all patients was 38.8 years, with a peak incidence in their 30s. The patient group included 33 (52.4%) males and 30 (47.6%) females. The tumor was most commonly on the trunk (n Z 28, 44.4%) followed by the lower extremities (n Z 16, 25.4%) and the head and neck (n Z 11, 17.5%) (Table 1). CD34 staining was performed in 30 patients and fount to be positive in 93.3% (28 patients).
Treatment outcomes The median follow-up period was 65 months (range 31e190 months) (Table 2). The marginal excision group had a recurrence rate of 35.7% (5 of 14), while groups II and III
Table 1
Patient demographics.
Sex Female Male Total Age (years) <20 21e30 31e40 41e50 51e60 61e70 >71 Location of the tumor Head and neck Trunk Chest, clavicle Abdomen Back Upper extremity Shoulder Arm and hand Lower extremity Groin Thigh Lower leg and foot CD34 staining Total Positive
Frequency
Percentage
30 33 63
47.6 52.4 100
4 15 20 12 6 5 1
6.4 23.8 31.8 19 9.5 7.9 1.6
11 28 10 7 11 8 5 3 16 3 6 7
17.5 44.4
30 28
12.7
25.4
93.3
3 showed no recurrence during the follow-up period. The marginal excision group had a significantly higher (p < 0.001, one-sided) recurrence rate than the wide local excision group. Tumor size, rate of head and neck tumors, and follow-up period did not differ among the three groups. The median sizes of the tumor were 9.75 (interquartile range 3e25), 4 (2.1e6.25), and 6.75 cm2 (interquartile range 2.25e17 cm2) for groups I, II, and III, respectively (p Z 0.186). The mean gross resection margins of groups II and III were 1.86 (range 0.5e2.5, SD: 0.73) and 3.68 cm (range 3.0e5.0 cm, SD: 0.76), respectively. Intraoperative frozen section analysis was performed in 35 out of 49 patients in the wide excision group (Table 3). Clear lateral margins were achieved at initial resection in 93.3% (14 out of 15 patients) of group II patients and 95% (19 out of 20 patients) of group III patients. Deep margins were positive for tumor cells in three patients at initial excision. Further excision at the location of positive margins resulted in clear margins of frozen biopsy in all patients (five patients) with positive frozen margins. The accuracy rate of frozen section analysis was 100% compared with the permanent sections. In the wide excision group, the rates of clear permanent margins in no-frozen biopsy group and frozen biopsy group were 85.7% (12 out of 14 patients) and 100% (35 out of 35 patients), respectively. Although it was not statistically significant, the no-frozen biopsy was associated with a trend toward increased odds of positive permanent margins (odds Z 1.167, 95% CI: 0.942e1.445, p Z 0.077, two-sided). Of the 10 patients with data for final pathologic margin in group I, seven patients (70%) had positive margins (Table 3). The rates of negative margin in the final pathologic results for groups I, II, and III were 30% (3 out of 10 patients), 95.2% (20 out of 21), and 96.4% (27 out of 28 patients), respectively (p Z 0.670, one-sided). All patients with negative margins had no recurrences. However, the recurrence rate in patients with positive margins after marginal excision was 42.8% (three out of seven patients). One patient each from groups II and III had focal positive lateral margins on permanent section analysis. The gross resection margins of the patients with positive margins were 0.8 and 4 cm, and intraoperative frozen biopsy was not performed for both of them. The two patients with positive margins declined further treatment, and were followed up for 70 and 124 months, respectively, and no recurrence was found. Radiation therapy was provided to six patients in group I (Table 4). Two patients with positive margin and one recurrent patient were included in this patient group. However, none of them experienced recurrence. On the contrary, recurrence rate of nonradiation group was 60% (6 out of 10 patients), and one patient recurred twice. One patient in group I underwent marginal excision thrice because of recurrence at 18 and 12 months postoperatively. The patient received adjuvant radiotherapy after the third surgery, and did not experience recurrence for over 14 years. Adjuvant radiotherapy was significantly associated with a reduced recurrence rate (p Z 0.016, one-sided). There was no serious complication from radiation therapy. The need for reconstructive surgeries such as skin graft or flap surgery was significantly higher in group III than group II (82.7% vs. 52.4%, p Z 0.011, one-sided).
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K.-J. Woo et al. Table 2
Outcomes of treatment.
Number of patients Recurrence, n (%) Median size of tumor, cm2 (IQR) Head and neck location, n (%) Median follow-up periods, months (IQR) Needs for reconstructive surgery, n (%)
Total
Group I
Group II WLE (<3 cm) Group III WLE (3 cm) P value
63 5 (7.9) 6 (2.2e13.7) 11 (17.5) 65 (47e108) 0
14 5 (35.7) 9.7 (3e25) 4 (28.6) 75 (60e122) 1 (7.1)
21 0 4 (2.1e6.2) 5 (23.8) 58 (45e84) 11 (52.4)
28 0 6.7 (2.2e17) 2 (7.1) 64.5 (46.5e103) 24 (82.7)
<0.001a 0.186b 0.140c 0.233b 0.011d
IQR, interquartile range; WLE, wide local excision. a Group I vs. (group II þ group III), one-sided, Fisher’s exact test. b KruskaleWallis test. c Two-sided, Fisher’s exact test. d Group II vs. group III, one-sided, Fisher’s exact test.
Discussion Surgical treatment modalities for DFSP In this study, marginal excision showed a high recurrence rate (35.7%). The rate of positive final pathologic margin was as high as 70% (7 out of 10). On the contrary, groups II and III showed no recurrence during a median follow-up of 60 months (range 31e190 months). Tumor size, rate of head and neck tumors, and follow-up period are potential confounders that can influence the recurrence rate. These variables did not differ between the three groups. In addition, Kimmel et al. reported that preoperative tumor size did not correlate well with true tumor extent.7 Our current experience provides supporting evidence that wide local excision should be a first-line surgical modality for DFSP. There has been no consensus as to what gross margin of excision constitutes proper surgical management. Wide local excision with gross resection margins of 3 cm has Table 3
Table 4 Effects of adjuvant radiotherapy on recurrences in marginal excision. No Radiotherapy Total P radiotherapy value
Microscopic margin status and recurrences. Group Group Group P value I II III
Total number of patients Intraoperative frozen biopsy, n Negative lateral margins at initial resection, n (%) Negative deep margins at initial resection, n (%) Negative permanent margins, n (%) Permanent margin status described, n Negative permanent margins, n (%) Recurrence in patients with negative margins, n (%) Recurrence in patients with positive margins, n (%) a
long been recommended as the standard treatment for DFSP.1,8 A meta-analysis of 98 patients found that a standard wide excision margin of 4 cm was predicted to provide a tumor clearance rate of 95%.7 A 5 cm of peripheral excision margin was performed in certain studies for wide local excision.18 However, a multidisciplinary approach and advances in pathologic technique have led to a recent reduction in recommended gross resection margins for DFSP (Table 5).1,7e12,18,19 Recent studies reported very low or no local recurrences after excision with <3-cm margins.11,12 In 1995, Parker et al. performed Mohs surgery to measure the subclinical extent of tumor and determine appropriate surgical margins and found that a 2.5-cm surgical margin removed all the tumors.19 Mohs surgery is an effective surgical modality for the treatment of DFSP.20e24 Mohs surgery minimizes surgical
14 0
21 15
28 20
e
14 (93.3) 13 (86.6) 15 (100) 21
19 (95) >0.999*
e e 10
19 (95) 20 (100) 28
3 (30) 20 27 0.679a (95.2) (96.4) 0 0 0
3 0 (42.8)
0
Two-sided, Fisher’s exact test between groups II and III.
Total cases, n Recurrence among total cases, n (%) Cases evaluated permanent margins, n Positive margins, n Negative margins, n Recurrence among positive margins, n (%) Recurrence among negative margins, n (%)
10 6 (60.0)
6 0
16a 6 0.016b (37.5)
6
4
10
5
2
7
1
2
3
3 (60.0)
0
3 (42.8)
0
0
0
a
Total surgical cases were 16 in 14 patients, a patient in group I got surgical treatment thrice because of recurrences. Adjuvant radiation was performed after the third surgery. b One-sided, Fisher’s exact test.
Please cite this article in press as: Woo K-J, et al., Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin, Journal of Plastic, Reconstructive & Aesthetic Surgery (2015), http://dx.doi.org/10.1016/ j.bjps.2015.10.027
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Surgical treatment for dermatofibrosarcoma protuberans Table 5
5
References regarding gross resection margins of DFSP.
Authors/Ref. No.
Year
No. of cases
Gross margins, mean
Follow-up period, mean
Recurrences (%)
Recommended gross resection margins for wide local excision
Kokkinos10 Hersant11 Farma12 Parker19
2014 2013 2010 1995
20 66 204 20
20 mm or 30 mm 18 mm (10e30 mm) 20 mm (5e30 mm) Mohs (5e25 mm)
5.6 years 30 months 64 months NS
0 0 1 NS
Kimmel7
2007
98
Systematic review
NS
NS
Monnier1
2006 2004 1997
Roses9
1986
<3 cm 3e5 cm 3 cm 5 cm 5 cm <2 cm 2 cm 3 cm
9.6 years
Chang8 Arnaud18
32 30 60 66 primary 41 recurred 50, total
47 7 16.70 0 4.80 41 24 20
20 mm 10e30 mm 10e20 mm 2.5-cm margin removed all the tumors 4-cm margins provided a tumor clearance rate of 95% 3 cm
margins, preserving cosmetically and functionally vital tissues.25 It is most useful in treating head and neck tumors.21 Systematic reviews and retrospective studies reported a lower rate of recurrence with Mohs micrographic surgery than wide local excision.21,24,26,27 On the contrary, it requires multiple excisions and takes more time than wide local excision.28 In addition, a specially trained surgeon and dermatopathologist are necessary for Mohs surgery.17 It is unclear whether Mohs surgery is superior to wide local excision.10,28 The choice between wide local excision and Mohs surgery should be based on tumor characteristics and institutional expertise in these modalities.28
Frozen biopsy and gross resection margin in wide local excision Frozen sections of skin are an effective tool for margin assessment of primary epithelial malignancies of the skin.17 The authors used intraoperative frozen section analysis to reduce the rate of incomplete excision. Further resection was performed in five patients and clear margins could be achieved. This adjunctive method could reduce peripheral excision margins without increasing the possibility of incomplete excision. In surgical resections for DFSP, the deep fascia (nonscalp) or periosteum (scalp) should be resected to remove all the tumors.19 Our case series showed that tumor cells could spread deeper than the deep fascia. Although DFSP is not an aggressive tumor, a deep subcutaneous punch or incisional biopsy for the diagnosis could facilitate vertical spread of the tumor cells. While controversy exists regarding the use of frozen sections in DFSP, frozen biopsy can be an effective way to obtain negative margins, particularly at the deep surface of the DFSP.29 In this study, frozen section assessment could permit reconstructive surgery concurrently with excision. It usually takes <30 min to analyze the frozen section.30 The
59 months 61 months 7.3 years
3 cm 5 cm 3 cm
accuracy of frozen section analysis varies from center to center, but there have been attempts to improve the quality of assessment by using high-quality, completely faced section.17,31 If the frozen biopsy is unavailable, magnetic resonance (MR) imaging can be useful for preoperative evaluation of the depth of infiltration and extent of the tumor.32,33 Permanent pathologic margins were comparable between groups II and III. One patient from each group had a positive lateral margin in the final report. The patient in group III underwent wide excision with a 4-cm resection margin following tissue expander surgery around the tumor for reconstruction. It was assumed that the expansion of the skin around the tumor could have influenced the spread of the tumor. Popov et al. analyzed the differences between gross and histological margins and found that a mean difference of 1.5 cm existed.34 In our case series, four patients in group II had resection margins <1 cm. Although they did not experience recurrence during the follow-up period, a resection margin <1 cm may lead to an increased risk of positive margins during initial excision. This study of long-term follow-up >5 years demonstrated that margins >3 cm for wide local excision did not vary in pathologic status or rate of recurrence, although those patients did have an increased need for reconstructive surgery. Wide local excision with margins <3 cm would be appropriate for initial excision. On the contrary, a <1cm margin may increase the rate of recurrence considering the difference between gross and histologic margins. Therefore, the authors recommend a gross resection margin of 1.5e2 cm with frozen biopsy for initial wide local excision.
Adjuvant radiation therapy Despite the inclusion of two patients with positive margin and one recurrent patient, no recurrence was found in
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patients who underwent adjuvant radiation following marginal excision (Table 4). On the contrary, 60% (6 out of 10 patients) without adjuvant radiation following marginal excision had recurrences (p Z 0.016, one-sided). This result suggests that adjuvant radiation therapy can serve as a treatment option for patients with positive margins, particularly when re-excision will cause severe cosmetic or functional problems. The first report on radiation therapy for DFSP was provided by Rinck et al., in 1982.35 Many studies have reported the positive role of adjuvant radiation therapy for DFSP.2,15,16,36 In the largest study, 53 patients received adjuvant radiation therapy with a local control rate of 93% at 10 years.37 However, none of these was a comparative study and the surgical modalities were heterogeneous. Although the number of patients was small, the authors performed direct comparison in group I patients who underwent the same surgical modality of marginal excision.
Treatment recommendations Treatment recommendations for DFSP were proposed in Figure 1. Initial wide local excision has a definite role in the treatment of DFSP, because inadequate initial treatment can result in larger and deeper recurrent lesions.38 Wide local excision should be considered if the initial treatment was marginal excision. A resection margin of 1.5e2 cm with intraoperative frozen section analysis is reasonable for an initial wide local excision. If the intraoperative frozen biopsy is positive, further resection with margins approximately 1 cm can be performed at the positive margin. The specimen is subjected to final pathologic evaluation, and the defect is closed primarily or covered by reconstructive surgery. Either re-excision or adjuvant radiation therapy can be a treatment option if the final pathologic margin is positive for tumor cells. Recurrent disease can also be managed by appropriate wide excision.38 The potential limitations of this study are as follows: surgeries were not performed by a single surgeon and the recurrence rate in groups II and III could not be compared statistically, because no recurrence was found. In spite of these limitations, this study is the first of its kind to compare long-term outcomes of three different surgical treatment methods. This study suggests that gross resection margins >3 cm had no benefits regarding treatment outcomes. In addition, the current study demonstrated the positive role of intraoperative frozen section analysis and adjuvant radiation therapy, and provided treatment recommendations for DFSP.
Conclusions Treatment recommendations for DFSP were proposed based on the long-term treatment outcomes and a literature review. A resection margin of 1.5e2 cm together with frozen biopsy is sufficient for an initial wide local excision. As DFSP is a radiosensitive disease, either re-excision or adjuvant radiation therapy can serve as a treatment option for patients with positive margins.
Figure 1 Treatment recommendations brosarcoma protuberans (DFSP).
for
dermatofi-
Conflicts of interest statement This study has no source of any financial or material support. There are no potential conflicts of interest for this study.
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Please cite this article in press as: Woo K-J, et al., Long-term outcomes of surgical treatment for dermatofibrosarcoma protuberans according to width of gross resection margin, Journal of Plastic, Reconstructive & Aesthetic Surgery (2015), http://dx.doi.org/10.1016/ j.bjps.2015.10.027