Dermatofibrosarcoma Protuberans (DFSP) is a rare, slow-growing cancer originating in the skin. Classified as a malignant cutaneous soft-tissue sarcoma, DFSP develops in the connective tissue cells within the dermis, the middle layer of the skin. The tumor is notable for its locally aggressive behavior, deeply infiltrating surrounding tissues. DFSP is considered a low-grade malignancy because it metastasizes to distant parts of the body in less than 5% of cases, though it poses a significant risk of returning after initial treatment.
Understanding This Rare Sarcoma
DFSP is categorized as an intermediate-grade sarcoma, reflecting its high tendency for local recurrence but low potential for distant spread. The tumor arises from fibroblast-like cells in the dermis, which produce connective tissue like collagen. This fibroblastic origin distinguishes DFSP from more common skin cancers like melanoma or basal cell carcinoma.
The tumor’s local aggressiveness stems from its highly infiltrative growth pattern, sending microscopic projections into surrounding healthy tissue. These extensions often invade deeper structures, including subcutaneous fat, fascia, and sometimes muscle or bone.
DFSP can appear anywhere, but it is most frequently found on the trunk (chest, back, and shoulders), accounting for approximately 40 to 70% of cases. The extremities (arms and legs) are the next most common sites, followed by the head and neck region. It is an uncommon cancer, with an estimated incidence of less than five cases per million people each year.
The Genetic Origin and Clinical Presentation
The underlying cause of most DFSP tumors is a specific genetic abnormality: a chromosomal translocation, typically t(17;22). This results in the fusion of two genes, COL1A1 (chromosome 17) and PDGFB (chromosome 22). This COL1A1-PDGFB fusion gene is found in over 90% of DFSP cases.
The resulting fusion protein acts as a constantly activated signal, leading to the overproduction of Platelet-Derived Growth Factor Beta (PDGFB). PDGFB is a potent mitogen that continuously stimulates the Platelet-Derived Growth Factor Receptor (PDGFR) on the tumor cells. This perpetual signaling drives the uncontrolled growth and proliferation of the cancerous cells.
Clinically, the tumor typically begins as a small, firm, reddish or purplish patch or plaque, often mistaken for a scar, bruise, or cyst. Because it is slow-growing, the initial lesion may persist for months or years before diagnosis. As the tumor progresses, it develops into one or more raised, hard nodules that protrude from the skin surface, the characteristic feature that gives the tumor its name, “protuberans.”
Confirming the Diagnosis
A definitive diagnosis of DFSP requires a deep biopsy for pathological analysis. Physicians perform a punch or excisional biopsy to ensure the sample extends through the dermis and into the subcutaneous fat layer, capturing the tumor’s full infiltration. Superficial biopsies are often inadequate and can lead to misdiagnosis.
Under the microscope, pathologists look for a dense proliferation of spindle-shaped cells arranged in a swirling, cartwheel-like pattern, known as a storiform pattern. The tumor cells typically show diffuse expression of the CD34 marker when stained using immunohistochemistry (IHC). This CD34 positivity is a key feature used to differentiate DFSP from other similar skin lesions.
To confirm the diagnosis, especially in atypical cases, specialized molecular testing is employed. Fluorescence In Situ Hybridization (FISH) or Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) detect the signature COL1A1-PDGFB gene fusion. This specific genetic rearrangement provides molecular confirmation of DFSP and helps rule out other soft-tissue tumors.
Current Approaches to Treatment
The primary treatment for localized DFSP is complete surgical removal of the tumor. The goal is to achieve tumor-free margins, ensuring no cancer cells are left behind. This is challenging because of the tumor’s microscopic extensions into the fat layer.
The preferred surgical technique is Mohs Micrographic Surgery (MMS). MMS allows for precise, layer-by-layer removal with immediate, complete margin control. This minimizes the amount of healthy tissue removed while ensuring the highest cure rate and lowest local recurrence rate (around 1%).
For large tumors or when MMS is unavailable, Wide Local Excision (WLE) is performed, removing the tumor with a large perimeter of healthy tissue (typically a 2 to 4 centimeter margin).
For unresectable, recurrent, or metastatic cases, targeted drug therapy is the standard systemic treatment. This approach uses imatinib, a tyrosine kinase inhibitor. Imatinib works by blocking the activity of the PDGFR receptor, shutting down the growth signal activated by the COL1A1-PDGFB fusion protein.
Imatinib may also be used as neoadjuvant therapy (given before surgery) to shrink the tumor, making subsequent surgical removal less extensive. Radiation therapy is another option, often used as an adjuvant treatment after surgery when clear margins cannot be confirmed or re-excision is not feasible. Radiation targets any remaining localized cancer cells, reducing the risk of recurrence.