Dermatofibrosarcoma protuberans

Did You Know?

• More than 90% of DFSP tumors carry the t(17;22) translocation, fusing COL1A1 with PDGF, creating a self-stimulatory growth signal.
• DFSP tissue is often positive for CD34.
• DFSPs may enlarge more rapidly during pregnancy, possibly due to expression of the progesterone receptor.

Presentation

DFSP begins as a firm skin area 1 to 5 cm in diameter, resembling a bruise, birthmark, or pimple. It grows slowly and is most often found on the torso, though it can occur anywhere. About 90 percent of DFSPs are low-grade sarcomas; 10 percent contain a high-grade sarcomatous component (DFSP-FS) and are considered intermediate-grade. Fewer than 5 percent metastasize, but local recurrence is possible. Patients are typically in their thirties at diagnosis, possibly due to diagnostic delay. Site distribution from SEER data (2000–2010): trunk 42%, lower extremity 21%, upper extremity 21%, head and neck 13%, genitals 1%.

Variants

The World Health Organization in 2020 classified fibrosarcomatous DFSP (DFSP-FS) as a specific form of intermediate (rarely metastasizing) fibroblastic and myofibroblastic tumors, and other variants as intermediate (locally aggressive) fibroblastic and myofibroblastic tumors. Bednar (pigmented) DFSP, representing 1–5 percent of all DFSP in people with high melanin pigments, contains melanin-rich dendritic cells and has the same metastatic risk as classic DFSP. Myxoid DFSP shows myxoid stromal degeneration. Giant cell fibroblastoma (juvenile DFSP) arises in childhood, may be associated with DFSP, and can transform or recur as DFSP. Atrophic DFSP resembles benign lesions like morphea or atrophic scar, behaves like classic DFSP, and has a high local recurrence rate if not completely excised. Sclerosing DFSP has low cellularity with collagen bundles interspersed with typical DFSP cells. Granular cell variant contains spindle cells mingled with lysosomal granular cells. Fibrosarcomatous DFSP is a rare, more aggressive variant with higher local recurrence and metastatic potential, though fewer than 5 percent metastasize.

Diagnostic delay and misdiagnosis

Because DFSP initially presents as a flat plaque without a protuberance, diagnostic delay is common. A 2019 study of 214 patients found a range from less than a year to 42 years before diagnosis (median four years). A majority of patients (53%) receive a misdiagnosis; the most frequent prebiopsy suspicions were cyst (47.2%), lipoma (14.0%), and scar (7.9%). An alternative term, dermatofibrosarcoma often protuberant, has been suggested.

Treatment

Treatment is primarily surgical, with chemotherapy and radiation therapy used if clear margins are not achieved. Mohs micrographic surgery (MMS) offers a high cure rate and lower recurrence if negative margins are obtained. Wide local excision (WLE) was the gold standard but is under reevaluation; in the United States, WLE may be suggested after MMS recurrence. Larger margins are recommended for WLE, which has a recurrence rate of about 8.5 percent. DFSP invades surrounding tissues in a tentacle-like fashion, and diagnostic delay can lead to inadequate initial resection, resulting in larger recurrent lesions. Radiation therapy is not first-line but is used if clear margins are not achieved. Imatinib mesylate, a tyrosine kinase inhibitor, was approved by the US FDA in 2006 for unresectable, recurrent, or metastatic DFSP. It inhibits PDGF-receptors and may be effective for tumors positive for the t(17;22) translocation.