Background

Dermatofibrosarcoma protuberans
Although DFSP may have been reported in the literature as early as 1890,
Darier and Ferrand first described it in 1924 as a distinct cutaneous disease
entity called progressive and recurring dermatofibroma. Hoffman officially
coined the term dermatofibrosarcoma protuberans in 1925. [1] Note the images
below.

Dermatofibrosarcoma protuberans (DFSP) merupakan tumor berupa plak atau

nodule yang tumbuh infiitratif, yang melibatkan kulit dan jaringan sub kutan. DFSP tersusun

oleh populasi sel-sel yang cenderung uniform, monomorfik, menyerupai fibroblas dan

fibrosit.

The cellular origin of DFSP is not clear. Evidence supports the cellular origin
being fibroblastic, histiocytic, or neuroectodermal. DFSP manifests partial
features of each. Therefore, many authorities suggest pluripotential progenitor
cells, such as undifferentiated mesenchymal cells, may be the origin of DFSP,
because they have the capacity to differentiate into all 3 cell types. [2]
Cultured DFSP tumor cells have increased growth in response to platelet-
derived growth factor (PDGF)–beta. Cytogenetic studies reveal specific
abnormalities in DFSP tumor cells, such as reciprocal translocations of
chromosomes 17 and 22, t(17;22), and supernumerary ring chromosomes
composed of interspersed sequences from bands 17(17q22) and 22(22q12).
These rearrangements fuse the collagen type I alpha 1 (COL1A1) and the
PDGF-beta chain (PDGFB, c-sis proto-oncogene) genes. The collagen
promoter drives COL1A1 and PDGFB fusion protein production. The fusion
protein is then processed into functional PDGF-B and subsequently interacts
with the PDGF receptor on the cell surface of DFSP tumor cells. The
activation of the PDGF receptor tyrosine kinase triggers the proliferation of
DFSP tumor cells. [2, 3, 4, 5, 6, 7, 8]

History

Physical Examination
Dermatofibrosarcoma protuberans (DFSP) usually presents as a large,
indurated plaque several centimeters in diameter. DFSP is composed of firm,
irregular nodules varying in color from flesh to reddish brown. Telangiectasia
may be apparent on the surface or at the periphery.
Sometimes, DFSP may present as a morphealike, atrophic, sclerotic,
violaceous plaque without nodularity that may ulcerate as it slowly increases
in size.

Mostly the tumor is mobile upon palpation; however, fixation to deeper structures such
as fascia, muscle, and bone may occur in the later stage of the tumor.
DFSP most commonly occurs on the trunk (42-72%), followed by the proximal
extremities (16-30%). DFSP rarely occurs above the neck (10-16%)  [1] and extremely
rarely on the breast. [19]

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. 

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.