Abstract

Pleomorphic sarcomas arising from dermatofibrosarcoma protuberans (DFSP) are rare and poorly characterized. DFSP is predominantly a superficial, intermediate-grade fibroblastic neoplasm with storiform architecture, which can undergo fibrosarcomatous transformation (FS-DFSP) with an increased rate of local recurrence and distant metastases. Herein, we report an FS-DFSP which undergoes high-grade transformation to a pleomorphic sarcoma in which we then characterize by capture based next generation sequencing. A 30-year-old woman presented with an 8.5 cm cutaneous and soft tissue right lower quadrant abdominal wall mass. CT imaging showed a heterogeneously hyperdense mass involving the superficial and deep subcutaneous tissue with extension through the superficial fascia. The resection specimen showed a spindled and pleomorphic sarcoma involving the skin and subcutis with a component of DFSP transitioning to FS-DFSP, as well as to pleomorphic sarcoma. The FS areas and pleomorphic areas both showed loss of CD34 by immunohistochemistry. Next generation sequencing was then performed to better characterize the tumor. The canonical DFSP COL1A1::PDGFB fusion was identified, confirming the high-grade transformation arose in a bona fide DFSP. NGS also revealed a homozygous/biallelic deletion of RB1, a likely pathogenic rearrangement in the TERT gene promoter, and a deleterious missense mutation in TP53 with loss of the wild-type allele. Additionally, there were numerous large chromosomal copy number changes including arm-level and whole chromosome gains and losses. Frank pleomorphic sarcomatous differentiation arising in an FS-DFSP is not well understood molecularly and prognostic information is lacking. However, a higher rate of local recurrence and invasion has been reported in pleomorphic sarcomatous transformation. Molecular characterization in combination with histopathologic findings can help alert the potential increased risk to patients with these types of lesions.

Financial Disclosure:
No current or relevant financial relationships exist.