Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue tumor that develops in the deep layers of the skin. It affects the mainly the skin, but may also be found in muscle or fat tissue, or may even spread deeper and into the bone tissue.
The tumor is extremely uncommon, with an incidence of 1 in 100 000 to 1 in a million. Only about a thousand cases are diagnosed each year in the US.
The tumor begins as a small patch of rough or wrinkled discolored skin that is firm to the touch, but not tender or painful. It may extend up to 5 cm in diameter and retain flesh color or turn reddish or purple.
Occurrence and Variants
DSFP occurs most often over the torso, but also over the legs or the arms, the head and the neck. The typical time of occurrence is in the thirties, but there is no bar on the age at which it may appear, with tumors being known to appear even in children. This may be particularly troublesome to intially spot in the latter population, as it may resemble a birthmark. The tumor is often asymptomatic, thus local spread may have already occurred by the time of diagnosis. Metastasis is rare, but when it is present, the lungs are often involved. The abdomen has been the site of metastasis in some rare cases.
Several variant forms of DFSP have been observed, including Bednar tumors or pigmented DFSP, which is characterized by pigmented melanin-containing dendritic cells. Another variant is myxoid DFSP containing abnormal myxoid stroma, which is more jelly-like than cellular. There is also giant cell fibroblastoma containing tumor giant cells, which is also called juvenile DFSP, because of its characteristic propensity to develop in childhood and adolescence.
In very rare cases, DFSP tumors may resemble fibrosarcoma. This is far more aggressive and the rate of metastasis is higher, for which reasons its diagnosis is therefore important. The tumor is then called fibrosarcomatous DFSP or FS-DFSP.
Risk Factors for DFSP
There is a current rise in the incidence of DFSP, especially among the white ethnic population. Among these, white people living in the Hawaiian Islands are showing the highest increase in risk. Yet, the overall risk of developing this tumor is highest in the black population, where the is an almost doubled incidence, especially of the Bednar tumor variant.
Women also have a slightly higher risk than males, and during pregnancy, the tumor grows faster than usual.
What Causes DFSP?
DFSP is now known to be associated in almost 90% of patients with a translocation of chromosomes 17 and 22 t(17;22). This is recirpocral abnormality is not inherited, but occurs in tumor cells, after birth.
The reciprocal translocation of genetic material between the chromosomes 17 and 22, involves the genes COL1A1 and PDGFB. This translocation results in the formation of an extra or supernumerary chromosome. This may be either linear or ring-shaped (circular). The sticky ends of the genes snipped off of these chromosomes join to form the ring chromosome.
The COL1A1 gene encodes the collagen type 1 protein. This is crucial for support and structural strength in most tissues and organs of the body, being a ubiquitous connective tissue molecule. On the other hand, the PDGFB gene is responsible for the synthesis of the platelet-derived growth factor in one form, a factor that promotes cell growth, maturation and proliferation.
The fusion of these genes causes an abnormal proliferation of cells from the affected or mutated cell. This is because the fused gene gives rise to excessive amounts of an abnormal fusion protein which, just like PDGF, acts as a growth and proliferation promoter. This in turn leads to tumor formation.
Other unidentified mutations may be responsible for the tumorous growth in the 10% of DFSP patients who lack the COL1A1-PDGFB fusion gene.
What Causes this Mutation?
It is currently thought that DFSP is the result of severe trauma to the skin cells in some cases. For instance, some tumors began on skin that was badly burned or injured, and others on irradiated skin or skin that showed vaccination scars. The nature of this risk is not yet clear.