Dermatofibrosarcoma protuberans (DFSP) is an uncommon low-grade sarcoma of the skin and soft tissue.1 The fibrohistiocytic tumor is derived from connective tissue cells called fibroblasts located in the dermis.2 Though slow-growing with low metastatic potential, DFSP is locally aggressive and tends to recur following surgical treatment.2 Given its indolent clinical course, diagnosis of DFSP is frequently delayed.
In the late 1800s, DFSP was recognized as a keloid sarcoma given its resemblance to keloids.3 In the early 1900s, the tumor was described as a progressive recurrent dermatofibroma by French dermatologist Ferdinand-Jean Darier (1856-1938).3 Shorty afterward in 1925, German dermatologist Erich Hoffmann (1868-1959) coined the modern term dermato-fibrosarcoma protuberans to describe the protuberant sarcomatous tumor.3
Comprising less than 0.1% of all malignancies, DFSP is relatively rare.4,5 Based on the Surveillance, Epidemiology, and End Results (SEER) program, the annual incidence of DFSP in the US population is estimated to be 4.1 to 4.2 cases per million people.4,5 The majority of cases occur among middle-aged adults, though cases have been reported across all age groups including children and older adults.4,5 The SEER-based epidemiologic studies also identified an increased incidence among Black individuals (6.5-7.1 per million) compared with White persons (3.6-3.9 per million).4,5 Men and women are affected at roughly the same ratio with some evidence of a slightly increased incidence among women.4,5
The cause of DFSP is unknown. A history of trauma or injury to the affected skin may be a predisposing factor.1 Factors associated with worse survival outcomes include increased age at diagnosis, male sex, Black race, and atypical anatomic locations such as the extremities and the head.5 Previous reports have suggested accelerated tumor growth during pregnancy.6 Biopsy specimens of DFSP appear to express low levels of hormone receptors such as progesterone receptors that may facilitate the rapid tumor enlargement observed in pregnant patients.6 In addition, multiple DFSPs have been reported in patients with immunodeficiency disorders, such as adenosine deaminase-deficient severe combined immunodeficiency in children.2
Although risk factors for DFSP remain obscure, multiple studies have identified a genetic basis for the tumorigenesis of DFSP. In the 1990s, scientists identified the reciprocal translocation t(17;22)(q22;q13) in a significant majority of DFPS specimens.7,8 This unique cytogenetic abnormality was found to result in the formation of a COL1A1-PDGFβfusion gene transcript. The resultant constitutive expression of the platelet-derived growth factor β (PDGFβ) protein is believed to drive the long-term self-propagation of DFSP cells.8 These discoveries eventually paved the way for the current use of targeted therapy against the PDGFβ receptor in the treatment of DFSP.8,9
This condition occurs most frequently on the trunk followed by the proximal extremities (including the shoulders and the pelvic region) and the head/neck region.1,4,5 The clinical and pathologic course of DFSP is divided broadly into 2 stages: plaque and nodular. In the plaque stage, an early nonprotuberant lesion with subcutaneous thickening may be observed.2,10 The lesion is usually asymptomatic and may be reddish-brown, reddish-blue, or skin-colored.2
On histopathologic analysis, spindle cells are loosely scattered in the upper dermis and CD34-positive on immunostaining.2 Over a span of months or years, the lesion enlarges into a cluster of indurated nodules or protuberances.2 Microscopically, spindle cells in the nodular stage are arranged in a storiform pattern, forming uniform short fascicles that infiltrate the subcutaneous tissue.2 If left untreated, tumor cells may invade more deeply and cause significant cosmetic disfigurement.2
Dermatofibrosarcoma protuberans may be difficult to clinically diagnose because it resembles many benign skin growths. Depending on the stage of the tumor (plaque or nodular) at the time of clinical presentation, the differential diagnosis for DFSP may include keloid, dermatofibroma, dermatomyofibroma, peripheral nerve sheath tumor (eg, neurofibroma, schwannoma), intradermal spindle cell/pleomorphic lipoma, and desmoplastic melanoma.2,10 To facilitate specific pathologic diagnosis, a generous biopsy (punch or excisional) should be performed to collect sufficient tissue for histopathologic evaluation.2 In immunohistochemistry studies, spindle cells in DFPS typically are strongly and diffusely positive for the marker CD34 and negative for other immunostains such as factor XIIIa, S-100, and α-smooth muscle actin.2,8,11 For difficult cases, molecular studies using fluorescence in situ hybridization (FISH) and reverse transcriptase–polymerase chain reaction (RT-PCR) are especially valuable in detecting specific tumor-associated chromosomal translocations and fusion gene transcripts.2
Once the diagnosis is confirmed, the initial treatment of DFSP is mainly surgical.1,10 Mohs micrographic surgery (MMS) is generally preferred over wide local excision in most cases because of the higher cure rate and lower recurrence rate associated with MMS.1,2 For patients with unresectable, recurrent, or metastatic DFSP, the oral chemotherapy agent imatinib mesylate has demonstrated long-term antitumor activity in DFSP characterized by the COL1A1-PDGFβ fusion gene.12 As an FDA-approved and well-tolerated treatment for DFSP in adults, this small molecule inhibitor functions by inhibiting PDGFβ receptors.12 Overall, the 5-year survival rate for DFSP is highly favorable (>99%).4,5
To promote early detection of local recurrence, follow-up examinations are recommended every 6 months for the first 5 years following diagnosis and every year thereafter.10 In addition to clinical examinations, imaging examinations with local ultrasound, magnetic resonance imaging (MRI), and/or computed tomography (CT), may be performed in patients with a history of disease recurrence.10
A punch biopsy taken from the lesion of the patient in this case was consistent with DFSP. Given the size and location of this lesion, she was referred for excision with surgical oncology with subsequent tissue reconstruction with plastic surgery.
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