Dermatofibrosarcoma protuberans with a novel COL6A3‐PDGFD fusion gene and apparent predilection for breast

Abstract

Dermatofibrosarcoma protuberans is a locally aggressive superficial mesenchymal neoplasm. It typically occurs in adulthood, and has been reported to have a slight male predilection. Tumors have a characteristic histopathologic appearance, including: storiform architecture, infiltrative "honeycomb" growth within subcutaneous adipose tissue, and immunoreactivity for CD34. Virtually all molecularly characterized cases to date have been found to harbor a COL1A1-PDGFB fusion product. Following identification of an index patient with a novel COL6A3-PDGFD fusion gene, we undertook a molecular investigation, using a combination of RNA sequencing and fluorescence in situ hybridization (FISH), to assess the prevalence of PDGFD rearrangement in dermatofibrosarcoma protuberans (N = 63). Three additional patients were found to have balanced PDGFD rearrangements. Interestingly, all 4 tumors arose on the breast of females. As a result, we subsequently examined 16 additional cases of primary breast dermatofibrosarcoma protuberans, identifying 2 additional tumors with PDGFD rearrangement. The morphology and immunophenotype of all 6 cases was analogous to those with the canonical COL1A1-PDGFB fusion; none of the cases showed fibrosarcomatous transformation. This study illustrates that the COL6A3-PDGFD fusion product is rare in dermatofibrosarcoma protuberans, and associated with an apparent predilection for breast. An awareness of this variant is important for pathologists, as it will not be detected using conventional reverse transcription polymerase chain reaction or FISH-based diagnostic assays for dermatofibrosarcoma protuberans.

Detection of CSF1 rearrangements deleting the 3′ UTR in tenosynovial giant cell tumors

“…RNA quality was assessed with the RNA 6000 Nano Bioanalyzer kit (5067‐1511; Agilent, Santa Clara, CA, USA) and quantitated using the Qubit RNA HS Assay Kit (Q32852; Thermofisher Scientific, Waltham, MA, USA). About 20 to 100 ng total RNA was used as input to prepare RNA‐seq libraries with the TruSight RNA Fusion Panel (RS‐304‐1002; Illumina, San Diego, CA, USA), following the manufacturer's instructions as previously described . Samples were sequenced using 76 base‐pair paired‐end reads on an Illumina MiSeq at eight samples per flow cell (approximately 3 million reads/sample).…”

S1 guidelines for dermatofibrosarcoma protuberans (DFSP) – update 2018

“…The gene product, a COL1A1‐PDGF‐β fusion protein, binds to the constitutively expressed PDGF receptor (PDGF‐R) and thus acts as an autocrine factor that continually stimulates growth of DFSP cells. A special DFSP variant is associated with a COL6A3‐PDGFD fusion gene and typically occurs on the breast of females . There have also been some reports of DFSP patients with an EMILIN2‐PDGFD fusion gene .…”

“…Das Genprodukt, ein COL1A1-PDGF-b-Fusionsprotein, wirkt auf die Zellen des DFSP über eine Bindung an den konstitutiv exprimierten PDGF-Rezeptor (PDGF-R) als autokriner kontinuierlicher Wachstumsstimulus. Eine Sonderform des DFSP geht mit einer CO-L6A3-PDGFD-Genfusion einher, und ist typischerweise an der Brust lokalisiert [7]. Ebenso sind seltene Fälle von DFSP margins of 1 to 2 cm.…”

S1‐Leitlinie Dermatofibrosarcoma protuberans (DFSP) – Update 2018

“…Das Genprodukt, ein COL1A1‐PDGF‐β‐Fusionsprotein, wirkt auf die Zellen des DFSP über eine Bindung an den konstitutiv exprimierten PDGF‐Rezeptor (PDGF‐R) als autokriner kontinuierlicher Wachstumsstimulus. Eine Sonderform des DFSP geht mit einer COL6A3‐PDGFD‐Genfusion einher, und ist typischerweise an der Brust lokalisiert . Ebenso sind seltene Fälle von DFSP mit einer EMILIN2‐PDGFD‐Genfusion beschrieben .…”