DERMATOFIBROSARCOMA
PROTUBERANS
Dermatofibrosarcoma protuberans is a rare cutaneous malignancy that is
locally aggressive. The tumor is derived from the dermal fibroblast, and it is
not believed to arise from previously existing dermatofibromas.
Dermatofibrosarcoma protuberans rarely metastasizes, but it has a distinctive
tendency to recur locally.
Clinical Findings: Dermatofibrosarcoma protuberans is a slow-growing,
locally aggressive malignancy of the skin. These tumors are low-grade sarcomas
and make up approximately 1% of all soft tissue sarcomas. The tumor is found
equally in all races and affects males slightly more often than females. Most
tumors grow so slowly that the patient is not aware of their presence for many
years. The tumor starts off as a slight, fleshcolored thickness to the skin.
Over time, the tumor enlarges and has a pink to slightly red coloration. It
slowly infiltrates the surrounding tissue, particularly the subcutaneous
tissue. If the tumor is allowed to grow long enough, the malignancy will grow
into the fat and then back upward in the skin to develop satellite nodules
surrounding the original plaque. This is often the reason a patient seeks
medical care. The tumor tends to grow slowly for years, but it can hit a phase
of rapid growth. This rapid growth phase allows the tumor to grow in a vertical
direction, and hence the term protuberans is applied. If medical care is
not undertaken, the tumor will to continue to invade the deeper structures,
eventually invading underlying tissue, including fascia, muscle, and bone.
Dermatofibrosarcoma protuberans is,
for the most part, asymptomatic in the initial phases of the tumor. As it
enlarges, the patient may notice an itching sensation or, less frequently, a
burning sensation or pain. As the tumor enlarges, patients often notice
tightness of the skin or a thickening sensation; however, this development is
so slow that most patients ignore it for many more months or even years. The
differential diagnosis is often between dermatofibrosarcoma protuberans and a
keloid or hypertrophic scar. The atrophic variant can often be confused with
morphea. One clue to the diagnosis of dermatofibrosarcoma is the loss of hair
follicles within the tumor region. The adnexal structures are crowded out by
the ever-expanding tumor. If the tumor is allowed to enlarge enough, it will
begin to outgrow its blood supply, and ulceration and erosions develop
thereafter. The tumors have ill-defined borders, and determining the extent of
the tumor clinically can be challenging or impossible. A punch biopsy of the
tumor leads to the appropriate pathological diagnosis. Metastatic disease is
uncommon; however, local recurrence after surgical excision remains an issue.
Pathogenesis: The exact pathogenesis is unknown. By genetic
chromosomal tissue analysis, these tumors have been found to have a reciprocal
translocation, t(17;22)(q22;q13.1), which is believed to be pathogenic in
causing the tumor. The exact reason for this translocation is unknown. The translocation
causes fusion of the platelet-derived growth factor B-chain (PDGFB) gene
with the collagen type I α1 (COL1A1) gene. This translocation directly
causes the PDGFB gene to be under control of the COL1A1 gene.
PDGFB is then overex-pressed, and it drives a continuous stimulation of its
tyrosine kinase receptor.
Histology: Dermatofibrosarcoma protuberans shows an
infiltrative growth pattern. It invades the subcutaneous fat tissue. The tumor
cells can be seen encasing adipocytes. The tumor is poorly circumscribed, and
its borders can be difficult to distinguish from normal dermis. The tumor
itself is made up fibroblasts arranged in a storiform pattern. These tumors
stain positively with the CD34 immunohistochemical stain and are negative for
factor XIII. These two stains are often used to differentiate
dermatofibrosarcoma protuberans from the benign dermatofibroma, which has the
opposite staining pattern. The stromolysein-3 stain is also used to help
differentiate the two tumors; it is positive in cases of dermatofibroma and
negative in cases of dermatofibrosarcoma protuberans.
Treatment: Because of the ill-defined nature of the tumors
and their often large size at diagnosis, wide local excision with 2- to 3-cm
margins is often undertaken. Postoperative localized radiotherapy has been used
to help decrease the recurrence rate. Imatinib has shown promise in
dermatofibrosarcoma protuberans as a treatment before surgery to help shrink
large or inoperable tumors. There has also been anecdotal success with the use
of imatinib in metastatic disease.
