Unilateral Primary Breast Dermatofibrosarcoma Protuberans with Negative COL1A1-PDGFB Fusion on Fluorescence In Situ Hybridization

Abstract Introduction/Objective Dermatofibrosarcoma protuberans (DFSP) is a superficial and locally aggressive cutaneous soft tissue sarcoma. In most patients, DFSP arises from the trunk and proximal extremities with breast being an uncommon location. Although they rarely metastasize (<5%), DFSP variants tend to recur locally. Most molecularly characterized cases have been defined by the translocation t(17;22)(q21.3;q13.1), which yields a fusion of the COL1A1 and PDGFB genes. In routine practice, dual fusion or break-apart fluorescence in situ hybridization (FISH) for the COL1A1-PDGFB fusion gene is the most widely used screening method for DFSP. However, in ~4% of typical DFSP cases, routine FISH screening is negative. In some of the DFSP cases negative for COL1A1-PDGFB fusion gene by FISH, RNA sequencing has identified two novel gene fusions, COL6A3-PDGFD and EMILIN2-PDGFD, with the former having a predilection for the female breast. Methods/Case Report We present a 32-year-old woman who underwent a biopsy for a 3.4 cm echogenic firm mass in her right breast. Histology showed a cytologically-uniform spindle cell neoplasm with fibroblastic morphology. The neoplastic cells displayed a storiform growth pattern and honeycomb-like infiltration of the adipose tissue. Immunohistochemically, the neoplastic cells expressed CD34 and vimentin and were negative for AE1/AE3, p63, S100, CD31, SMA, β-catenin, and STAT6. PDGFB break-apart FISH was negative. Based on the histologic and immunohistochemical findings, a diagnosis of DFSP was rendered. FISH for PDFGD rearrangements or RNA sequencing targeting PDGFD was not performed at this time. Results (if a Case Study enter NA) NA. Conclusion Awareness is warranted for the rare variant of DSFP with a predilection for female breast, which is characterized by a novel gene fusion not detectable by routine FISH used for DFSP screening.