Dermatofibrosarcoma Protuberans
Diagnosis and treatment of DFSP
Obligatory—This is not medical advice
Dermatofibrosarcoma protuberans (DFSP) is one of a few different types of primary cutaneous (of the skin) sarcoma. DFSP is derived from dermal fibroblasts, which are mesenchymal cells. DFSP is the second most common sarcoma of the skin to Kaposi Sarcoma. Even though DFSP is rare, there are established forms of treatment, and outcomes are generally well understood. We’ll review the diagnosis as well as what we know about systemic treatment of advanced disease further, below.
Epidemiology and Diagnosis
Usually, patients will first notice a minimally symptomatic skin lesion that grows slowly over time. The reported incidence is 4.1 per million person-years.1 This indicates slightly more than 1000 new diagnoses annually in the United States. In a 2016 review of the Surveillance, Epidemiology and End Results Registry of the NCI2, 3686 patients with DFSP were included. The mean age was 43.6 years of age, and the median tumors size was 3.0 cm. There was a large standard deviation for each, and so we might see wide variances in size and age. The most common site of diagnosis was the trunk at 49.2%, compared with 37.7% in extremities, and 13.1% in the head and neck. The ten-year survival rate was 99.1%.
After a biopsy is performed, the microscopic appearance of DFSP usually is spindle cells with little atypia and few mitoses (see figure below). Because histologic of neoplastic cells may not be striking, it may sometimes be difficult to clearly delineate margins. As far as staining is concerned, it is positive for CD34 expression, however, this can sometimes be lost in higher grade, or fibrosarcomatous DFSP. Classic DFSP accounts for about 90% of all DFSP. Fibrosarcomatous DFSP has a higher-grade appearance with more atypia and increased mitoses.3
Molecular studies now show that more than 90% of cases of DFSP involve a fusion protein that incorporates COL1A1 and PDGFRB (17q22; 22q13). This leads to continued stimulation of PDGFR receptor with an autocrine mechanism, and therefore growth of DFSP.4
After diagnosis, imaging may be considered depending upon characteristics of the tumor. For DFSP with fibrosarcomatous changes, imaging should be performed in line with soft tissue sarcoma guidelines (contrasted CT imaging).
Treatment
For localized disease, preferred treatment is resection with negative margins. Given the varied locations and sizes of DFSPs, the type of surgery performed is very much dependent upon the tumor itself. It is rare that DFSP spreads to lymph nodes, and so nodal dissection is not usually recommended. What is necessary, however, is negative margins. Should positive margins be found, there is a role for re-resection. This is because with conservative, or undefined margins, recurrence rate may be as high as 60% (see table below). 5 With negative margins, recurrence rates are less than 10%.
For patients with advanced disease, and therefore unlikely to benefit from surgery, we often rely on imatinib. In fact, imatinib has an FDA approval for this indication.6 The initial FDA approval took place in 2006 and data from EORTC and SWOG trials were published in 2010.7
Each trial was a single arm, two-stage phase II study, and combined, they accrued 24 patients. The selection criteria were similar, but not identical, which leads to some confusion. The two studies also had differing starting doses. The EORTC trial had a starting dose of 400 mg twice daily, while the SWOG trial was 400mg daily. One trial evaluated progression-free rate at 14 weeks, while the SWOG trial evaluated response rate by RECIST v1.0. Because of this, it may be difficult to interpret these varied results. Nonetheless, let’s remark on what they saw.
The table above demonstrates the response rate at 14, or 16 weeks. This is the probably the most reliable endpoint from these trials, as afterwards surgical intervention could influence outcomes. Within this context, the rate of partial response was 37.5% (that is percentage of patients in that time window that had a reduced size of the diameters of their cancers by more than 30%).
You can see that some patients remained on therapy for years. Keep in mind that numbers are very small. Toxicity of imatinib was comparable to that seen for other diagnoses and has been better covered elsewhere. Understandably, with small numbers and varied context, questions still remain about the usage of imatinib for patients with DFSP. In particular, we wonder about adjuvant (after surgery) or neoadjuvant (before surgery) administration of imatinib.
Despite the small numbers accrued, imatinib has become the standard first line therapy for patients who have advanced DFSP.
Conclusions
Dermatofibrosarcoma Protuberans is a cutaneous sarcoma that may have varied appearance histologically. Surgery with negative margins is curative for the vast majority of patients with low grade and localized disease. Fibrosarcomatous dermatofibrosarcoma protuberans has a higher rate of recurrence and more aggressive behavior. For patients with unresectable or metastatic dermatofibrosarcoma protuberans, and a COL1A1/PDGFRB fusion, imatinib should be considered preferred treatment in the first line. There continues to be a need for more medications in the later line setting for our patients with dermatofibrosarcoma protuberans.
https://pubmed.ncbi.nlm.nih.gov/26730971/
https://jamanetwork.com/journals/jamadermatology/fullarticle/2525544
https://link.springer.com/chapter/10.1007/978-3-642-05072-5_13
https://pubmed.ncbi.nlm.nih.gov/19205737
https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021588s024lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/20194851/
I believe that getting diagnosed is the difficult part of the treatment for dermatofibrosarcoma. Medical gaslighters will typically pass it off as a lipoma.