Medical Care
Currently, conventional chemotherapy is rarely used in the treatment of dermatofibrosarcoma protuberans (DFSP). Limited case reports have not shown any significant value of conventional chemotherapy in the treatment of DFSP. [30, 31]
Radiation therapy (RT) has had a limited role in the past, but, recently, it has been used as an adjunct to surgery. Radiation therapy may be recommended for patients if the margins of resection are positive or for situations in which adequate wide excision alone may result in major cosmetic or functional deficits. Postoperative adjuvant RT may reduce the risk of recurrence when clear surgical margins are not confident. [32] The complete radiation therapy dose ranges from 50-70 Gy. Overall, the risk of severe complications from RT is low. Close follow-up care after radiation therapy is warranted because some DFSP tumors may become more aggressive. [1, 14, 33, 34]
Based on the knowledge that constitutively activated PDGFB-PDGFR-beta signaling pathway plays a central role in the proliferation of DFSP tumor cells, the development of molecularly targeted therapy holds promise as an additional treatment option. [35] Originally approved for the treatment of chronic myelogenic leukemia, imatinib mesylate has been found to have significant therapeutic value in the treatment of DFSP. [36] Imatinib is a potent and specific inhibitor of several protein-tyrosine kinases, including the platelet-derived growth factor (PDGF) receptors. [5, 37]
On October 19, 2006, the US Food and Drug Administration granted approval for imatinib mesylate (Gleevec) as a single agent for the treatment of DFSP. Imatinib mesylate is indicated for the treatment of adult patients with unresectable, recurrent, and/or metastatic DFSP. The recommended oral dose is 800 mg/d. [16, 38]
With limited clinical data to date, a response rate of approximately 65% has been achieved among DFSP patients treated with imatinib. A small subset of DFSP patients lacking the classic t(17,22) gene aberration seems to have no response to imatinib. [1]
Neoadjuvant imatinib therapy for DFSP has been proposed in recent studies. [25, 39] Using imatinib as a preoperative therapy agent in locally advanced or recurrent DFSP may decrease tumor load, promote tumor cell apoptosis, and subsequently reduce the extent of surgery. Caution should be used when applying such a therapeutic strategy, because the potential exists for creating a skip area wherein discontiguous tumor may obscure the accurate pathology assessment of surgical margins.
Surgical Care
Surgical excision remains the mainstay of treatment for dermatofibrosarcoma protuberans (DFSP). [40] Despite controversy, Mohs micrographic surgery has been increasingly accepted as the treatment of choice, while others advocate wide local excision. [13, 34, 41, 42, 43] The fundamental difference of these two techniques is the pathology processing. Usually, the specimen from wide excision is sectioned in conventional bread-loaf fashion, while the Mohs specimen is freshly frozen and sectioned en face along the margins. Mohs surgery requires less tissue removal and allows complete margin assessment. However, large tumor can be a challenge for this very time-consuming procedure.
Because of its infiltrating growth pattern, DFSP commonly extends far beyond the clinical margins; this accounts in part for the high recurrence rate after standard surgical excision. [44] Hence, a wide excision of 2-3 cm or more of the margins beyond clinically identifiable tumor border, down to and including the fascia, is recommended for the treatment of DFSP. [13, 32, 41] Despite wide local excisions, an average recurrence rate of 15.7% is still observed among 1201 body cases and 51.8% is observed among 193 head and neck cases, as reported in the literature since 1951. A superior cure rate (an overall average recurrence rate of 1.3% among 463 cases reported) and tissue conservation are seen when Mohs micrographic surgery is used; thus, Mohs micrographic surgery is now considered the treatment of choice, [45] particularly when a lesion is located in the head and neck region. [18, 41, 46, 47, 48, 49, 50, 51]
Although some Mohs surgeons consider it unnecessary, taking an extra layer of tissue around the surgical defect at the completion of Mohs surgery for permanent pathology section and/or CD34 immunostaining may potentially enhance the cure rate. Alternatively, some have adopted modified Mohs techniques, or so-called "slow Mohs," by using rush paraffin sections instead of a fresh tissue technique. [46, 49, 52, 53, 54] Mohs surgery may not be readily accessible in many parts of the world. The physician should exercise clinical judgment to offer the best treatment available for the patient and consider multidisciplinary collaboration. Studies have demonstrated a low recurrence rate after surgery for DFSP if a multidisciplinary approach and careful pathology margin assessment are used. [55, 56]
Consultations
In dermatofibrosarcoma protuberans (DFSP), an informative consultation includes proper staging, prognostic evaluation, explanation of treatment options, and planning. All these depend on thorough history taking and physical examination. Imaging studies may facilitate the assessment of local invasion and distal metastasis. Multidisciplinary collaboration between a dermatologist, surgical oncologist, plastic surgeon, medical oncologist, radiation oncologist, and pathologist is necessary in locally advanced, recurrent, or metastatic cases of DFSP.
Long-Term Monitoring
Because of the high local recurrence rate of dermatofibrosarcoma protuberans (DFSP), patients require close follow-up care after treatment. Most recurrences occur within 3 years of the primary excision. Patients should be seen every 6 months during this period and annually thereafter. [14]
A literature review of DFSP case series treated with Mohs surgery shows that 50% of recurrences appear within the first 3 years after operation and 25% of local recurrences are detected after 5 years. A large case review from a series of 159 patients treated at Memorial Sloan-Kettering Cancer Center (New York) showed the medium time to the development of a local recurrence was 32 months. The indolent nature of DFSP requires lifelong surveillance for recurrence. [18]
In each follow-up visit, a complete history and a review of systems, as well as complete physical examinations, including skin examination and palpation of the excision site and regional lymph nodes, should be performed. An extensive workup is not warranted unless metastatic disease is suspected.
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Dermatofibrosarcoma protuberans manifesting as an irregular red-to-violaceous plaque on the chest.
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Closer view of dermatofibrosarcoma protuberans. It has an irregular surface and borders with palpable dermal and subcutaneous induration.
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A large dermatofibrosarcoma protuberans is seen on the abdomen. It has an appearance of atrophic plaque, while foci of nodularity also can be seen.
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Bednar tumor, a pigmented variant of dermatofibrosarcoma protuberans, contains melanin-rich dendritic cells scattered among neoplastic spindle-shaped cells.
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A featureless reddish brown plaque on the arm of a white female. Another example of Bednar tumor.
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Dermatofibrosarcoma protuberans (DFSP) tumor cells take over the dermis and subcutaneous adipose tissue and then approach the fascia plane. The tumor nodule manifests with high cellularity. Under histopathologic examination, these DFSP tumor cells are spindle shaped. They tend to grow in a storiform pattern in the center portion of the tumor. They may also grow in a diffuse infiltrative pattern at the periphery, forming a honeycomb pattern. Often, no defined border can be recognized between the tumor and normal tissue.
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Higher-power view of dermatofibrosarcoma protuberans reveals subcutaneous adipocytes entrapped by densely infiltrative spindle-shaped tumor cells.
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DFSP demonstrates strong CD34 staining with immunohistochemistry.
