Dermatofibrosarcoma protuberans recurrence: Size matters

By Warren R. Heymann, MD, FAAD
April 24, 2024
Vol. 6, No. 17

Editor’s note: An abridged version of this commentary was published in the November 2023 issue of the Journal of the American Academy of Dermatology.

Dermatofibrosarcoma protuberans (DFSP) is a fascinating soft tissue tumor; although considered uncommon, with an overall annual incidence of 4.2 per million accounting for 0.1% of all cancers. (1) I believe that those numbers may be an underestimate. With those statistics, one might expect never to encounter a DFSP — I have seen several such patients in my practice, even reporting a case. (2) I suspect that many DWI&I readers have also diagnosed patients with a DFSP. DFSP has a meager metastatic potential but exhibits highly aggressive tissue infiltration with a propensity for local recurrence. (3) This commentary focuses on the risk of DFSP recurrence.

DFSP characteristically presents as an asymptomatic, skin-colored to red-brown indurated plaques, which may develop multiple raised violaceus to red-brown nodules. DFSPs most often develop in the third to fifth decade of life. The pigmented variant of DFSP (Bednar tumor) and the fibrosarcomatous variant account for < 5% and up to 15% of cases, respectively. Although lesions grow slowly, they can reach several centimeters in diameter. The atrophic variant presents as a violaceous plaque that may resemble morphea or a scar. DFSPs may be mimicked clinically by a dermatofibroma, keloid, lipoma, or abscess, particularly in its early stages. (3,4) As lesions grow, some can ulcerate and become painful. Most DFSPs occur on the trunk (50%), followed by the extremities (35%) and head and neck (15%). The shoulder and pelvic region are particularly characteristic areas for DFSPs. DFSPs usually involve the subcutaneous fat but, if longstanding or recurrent, may extend into fascia, muscle, or bone. DFSPs have relentless growth with asymmetric, root-like projections, which cannot be appreciated on clinical exam, explaining the significant risk of local recurrence following excision. Distant metastasis is rare, occurring in 1% to 4% of cases and usually only after multiple local recurrences. The lung is the most common site of metastasis via hematogenous spread. Regional lymph nodes are rarely involved. The fibrosarcomatous variant of dermatofibrosarcoma protuberans has a higher risk of local recurrence (14% to 52%) and distant metastases (8% to 29%). (4)

Histologically, DFSP is characterized by a dense proliferation of uniform spindle cells with limited pleomorphism and low mitotic activity. Most DFSPs (80%–100%) stain positively with the mesenchymal cell markers CD34 and vimentin, but are negative for factor XIIIA, desmin, smooth muscle actin, S100, and keratin. Subtypes of DFSP include giant cell fibroblastoma, pigmented (Bednar), atrophic, sclerosing, myxoid, myoid, granular cell, and fibrosarcomatous transformation. (4)

As Vindal et al eloquently explains: “The pathogenesis of the tumor results from a chromosomal translocation t(17;22) (q22;q13) resulting in the fusion of collagen type Iα1 gene (COL1A1) and platelet-derived growth factor-beta polypeptide gene (PDGFB) leading to the formation of COL1A1-PDGFB fusion transcripts. This causes the upregulation of PDGFB and continuous activation of platelet-derived growth factor receptor-beta leading to proliferation of cells and tumor formation.” (5) This observation, noted in up to 95% of DFSP cases, led to the FDA-approved use of the tyrosine kinase inhibitor imatinib to treat unresectable, recurrent, and/or metastatic DFSP. (In smaller studies, other tyrosine kinase inhibitors such as sorafenib and pazopanib have demonstrated efficacy.) (3) For more detailed information about the pathogenesis of DFSP please see the prior DWI&I commentary on the topic.

The cornerstone of DFSP treatment is surgical removal, preferably with Mohs micrographic surgery (MMS) over wide local excision because of its high cure rate and maximal tissue conservation. (6) In their systematic review of MMS for DFSP, Foroozan et al concluded: “A weak recommendation is given in favor of MMS or similar surgical techniques with meticulous histologic evaluation of all margins as the first-line therapy for DFSP, particularly in recurrence-prone regions.” (7) DFSP is a radio-responsive tumor; adjuvant radiation should be considered for patients with large or recurrent tumors or when attempts at wide surgical margins result in significant morbidity. (8) The risk of recurrence of DFSP is highest in the first 3 postoperative years, and patients should be followed carefully during this time. (4) Recurrent DFSP is managed similarly to primary DFSP with tumor resection until margins are negative. (3)

Regarding the prognosis of DFSP, in their population-based cohort study of 3,686 DFSP cases, older age, male sex, and tumor size were significantly associated with worse overall survival in a controlled analysis. The treatment modality did not influence overall survival — of note, the treatment modality may be influenced by race, sex, and socioeconomic status. For example, it has been noted that Black patients may have higher mortality from DFSP than white patients. When the authors controlled for the size of the lesions, Black patients presented with larger lesions than white patients. Perhaps there was a delay in diagnosis (and treatment) if such lesions were mistakenly diagnosed as keloids. (9) Chen et al used population-based data with a total of 5,640 (74.53%) and 1,927 (25.47%) DFSPs of the skin and soft tissue, respectively. Independent risk factors for cancer-specific mortality included age at diagnosis, histologic grade, and tumor size. Patients with tumors ≥10 cm in size or histologic grade III had significantly higher DFSP-specific mortality (7.07% and 10.08%, respectively, p < .001). Tumor locations and surgical procedures did not significantly influence survival. The authors concluded that DFSP patients have a favorable survival prognosis, even in cases with node-positive or distant metastases. DFSP-specific mortality is significantly higher in patients with grade III or large (≥10 cm) tumors. (10) Baig et al analyzed data on 4451 DFSP patients from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, noting that 56 (1.26%) had recurrences, 52 (1.17%) had a DFSP-specific death. The risk of recurrence/DFSP-specified death in patients with large tumor sizes (≥3cm) was 2.60-fold higher than in patients with small tumor sizes (p = 0.007). (11)

The future of DFSP prognostication — as in all of medicine — may be based on artificial intelligence. Cao et al performed a retrospective study of 146 DFSP patients with MRI scans, comparing those images to the Ki67 index (a histological proliferation index assessing tumor aggressiveness). The authors determined that machine learning-based radiomics of features derived from MRI images were helpful for the accurate prediction of local recurrence of primary DFSP after surgical treatment and were better in predicting performance than the Ki67 index. (12)

Point to Remember: Dermatofibrosarcoma protuberans can be locally destructive and may rarely be fatal. Having the lesion excised (preferably with Mohs micrographic surgery) is the definitive foundation of treatment. Patients with large lesions stand a higher risk for recurrence and should be followed carefully in the postoperative period and beyond.

Our expert’s viewpoint

Randall K. Roenigk, MD, FAAD
Robert H. Kieckhefer Professor in Dermatology
Mayo Clinic
Rochester, Minnesota

There are phrases that could have been added to the title of this nice summary of DFSP. Correctly noted are the clinicopathologic variants of DFSP so I might also have added “…Histologic Subtype Matters.” In one patient, I removed a longstanding Bednar Tumor measuring 20 cm with one stage of Mohs Micrographic Surgery (MMS) and closed it primarily, while in another with a 5 cm DFSP atrophic variant it took eight stages and invaded the rectus abdominus muscle. But the need for a different approach to the fibrosarcomatous (FS) variant of DFSP remains unproven because there are too few cases published and the results anecdotal.

DFSP typically occurs on the trunk, but I have removed them from the face, genitals, and extremities. In cases like that I encountered anatomy with which our surgical colleagues in other specialties are much more comfortable. So, the title might also include “…Anatomic Site Matters.” (13) In addition, DFSP occurs in children and can even be present at birth. In those cases, not only is the anatomy different but the risks associated with anesthesia are greater. So, while much less common than the adult variant of DFSP, one might add “… Age Matters.” (14)

What matters most is the specialized approach to surgical margins offered by MMS, which is uniquely important for DFSP. (6, 15) Recurrence of DFSP in all settings is principally associated with incomplete tumor removal, allowing it to continue its slow growth to other organ systems and occasionally cause death. Our group pointed this out in a Letter to the Editor about an article published in the American Journal of Clinical Oncology. (16) The authors of that study found that after surgery for DFSP, positive margins were present 21.4% of the time in the wide excision (WE) group versus 0% in the MMS group, that there were significantly longer operative times in the MMS group, and that reconstruction was less complex in the WE group. The authors concluded that WE is a faster treatment, results in fewer complex closures, with similar local control compared with the MMS group (WE local recurrence rate of 3.6% vs. MMS of 0%). We wrote that these conclusions were unfounded and misleading, yet there remains a bias for WE in certain practice settings.

Whether a dermatologist with special expertise in MMS is treating routine BCC/SCC, using immunostains for melanoma or managing DFSP, Extramammary Paget’s and a host of large, unusual tumors, especially in the immunosuppressed population; “Size Matters.” I once surgically managed a huge BCC that invaded the inner cortex of the skull resulting in a pneumocephalus. It was a great comfort to the patient and me to have neurosurgery, plastic surgery, and the Neurological ICU available to effectively manage this case. These kinds of complications are often associated with DFSP because of its slow, insidious growth pattern, especially when unrecognized for years as is so often the case. One result of surgery for DFSP after MMS is a larger defect than anticipated but it may also be smaller. Since the first goal of any oncologic operation is to cure the tumor, either outcome is acceptable for DFSP and must be planned for preoperatively.

1. Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. 2007 Jun;56(6):968-73. doi: 10.1016/j.jaad.2006.09.006. Epub 2006 Dec 1. PMID: 17141362.

2. Green JJ, Heymann WR. Dermatofibrosarcoma protuberans occurring in a smallpox vaccination scar. J Am Acad Dermatol. 2003 May;48(5 Suppl):S54-5. doi: 10.1067/mjd.2003.168. PMID: 12734474.

3. Vitiello GA, Lee AY, Berman RS. Dermatofibrosarcoma Protuberans: What Is This? Surg Clin North Am. 2022 Aug;102(4):657-665. doi: 10.1016/j.suc.2022.05.004. PMID: 35952694.

4. Brooks J, Ramsey ML. Dermatofibrosarcoma Protuberans. 2023 Apr 14. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 30020677.

5. Vindal A, Lal T, Gupta Y, Kale AR, Lal P. Recurrent dermatofibrosarcoma protuberans: A report of two cases involving the trunk and abdominal wall. J Cancer Res Ther. 2023 Jan-Mar;19(2):498-500. doi: 10.4103/jcrt.jcrt_125_21. PMID: 37313924.

6. 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 Jul;35(1):82-7. PMID: 8682970.

7. 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 Sep;148(9):1055-63. doi: 10.1001/archdermatol.2012.1440. PMID: 22986859.

8. 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 Jul 1;86(3):585-90. doi: 10.1016/j.ijrobp.2013.02.024. Epub 2013 Apr 26. PMID: 23628134.

9. Criscito MC, Martires KJ, Stein JA. Prognostic Factors, Treatment, and Survival in Dermatofibrosarcoma Protuberans. JAMA Dermatol. 2016 Dec 1;152(12):1365-1371. doi: 10.1001/jamadermatol.2016.1886. PMID: 27262160.

10. Chen S, Xiong L, Zhao L, Li Y, Li L. Survival Outcomes and Prognostic Factors of Dermatofibrosarcoma Protuberans: A Population-Based Retrospective Cohort Analysis. Dermatol Surg. 2023 Jun 22. doi: 10.1097/DSS.0000000000003853. Epub ahead of print. PMID: 37384896.

11. Baig IT, Lauck K, Nguyen QD. Tumor Size is the Most Significant Risk Factor for Local Recurrence in Dermatofibrosarcoma Protuberans: A Large-Scale Retrospective Cohort Analysis. J Am Acad Dermatol. 2023 Jul 5:S0190-9622(23)01264-1. doi: 10.1016/j.jaad.2023.06.044. Epub ahead of print. PMID: 37419185.

12. Cao C, Yi Z, Xie M, Xie Y, Tang X, Tu B, Gao Y, Wan M. Machine learning-based radiomics analysis for predicting local recurrence of primary dermatofibrosarcoma protuberans after surgical treatment. Radiother Oncol. 2023 Jun 12;186:109737. doi: 10.1016/j.radonc.2023.109737. Epub ahead of print. PMID: 37315580.

13. Saifuddin H, Yan M, Jakub J, Martinez-Jorge J, Roenigk R, Vijayasekaran A. Wide local excision, Mohs micrographic surgery, and reconstructive options for treatment of dermatofibrosarcoma protuberans of the breast: A retrospective case series from Mayo Clinic. World J Surg Oncol. 2023 May 6; 21 (1):141 Epub 2023 May 06 PMID: 37147611 PMCID: 10163742 DOI: 10.1186/s12957-023-03022-9.

14. Brough KR, Youssef MJ, Winchester DS, Baum CL, Sharaf BA, Roenigk RK. Mohs micrographic surgery for dermatofibrosarcoma protuberans in 7 patients aged 10 years and younger. J Am Acad Dermatol. 2022 Jun; 86 (6):1429-1431 Epub 2021 June 29 PMID: 34214620 DOI: 10.1016/j.jaad.2021.06.856 .

15. Lowe GC, Onajin O, Baum CL, Otley CC, Arpey CJ, Roenigk RK, Brewer JD. A Comparison of Mohs Micrographic Surgery and Wide Local Excision for Treatment of Dermatofibrosarcoma Protuberans with Long-Term Follow-up: The Mayo Clinic Experience. Dermatol Surg. 2017 Jan; 43 (1):98-106 PMID: 27749444 DOI: 10.1097/DSS.0000000000000910.

16. Brewer JD, Roenigk RK, Otley CC. Wide local excision or Mohs micrographic surgery for primary dermatofibrosarcoma protuberans. Am J Clin Oncol. 2011 Oct; 34(5):545-6. PMID:21946674 DOI:10.1097/COC.0b013e3181f47942.

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