Novel TNC-PDGFD fusion in fibrosarcomatous dermatofibrosarcoma protuberans: a case report

Abstract

Background Dermatofibrosarcoma protuberans (DFSP) is a superficial fibroblastic tumor characterized by high rate of local recurrence and low metastatic potential. Fibrosarcomatous transformation can rarely arise in DFSP either de novo or as recurrent, which represents a form of tumor progression and carries an increased risk of metastasis over classic DFSP. Cytogenetically, DFSP is characterized by a recurrent unbalanced chromosome translocation t (17;22)(q22;q13), leading to the formation of COL1A1-PDGFB fusion transcript that is present in more than 90% of cases. Alternative fusions involving the PDGFD with partners of COL6A3 or EMILIN2 have recently been documented in less than 2% of cases. Herein, we report a DFSP with fibrosarcomtous morphology harboring a novel TNC-PDGFD fusion. Case presentation A 54-year-old female presented with a slowly growing mass in the right thigh. Excision demonstrated a 2-cm ovoid, well-circumscribed, gray-white, mass. Microscopic examination revealed a partially encapsulated subcutaneous nodule without dermal connection. The neoplasm was composed of cellular and fairly uniform spindle cells with brisk mitoses, arranged in elongated fascicles and herringbone patterns, with focal collagenized stroma. The neoplastic cells were positive for CD34 and smooth muscle actin. Fluorescence in-situ hybridization analyses showed negative for COL1A1-PDGFB fusion as well as NTRK1/2/3 rearrangements. A subsequent RNA sequencing detected an in-frame fusion between exon 15 of TNC and exon 6 of PDGFD. This fusion was further confirmed by nested reverse transcription polymerase chain reaction amplification followed by Sanger sequencing. A diagnosis of fibrosarcomatous DFSP was rendered and the patient was in good status at a follow-up of 12 months after the operation. Conclusions We report a fibrosarcomatous DFSP with novel TNC-PDGFD fusion, which adds to the pathologic and genetic spectrum of PDGFD-rearranged DFSP.

Pediatric dermatofibrosarcoma protuberans: A clinicopathologic and genetic analysis of 66 cases in the largest institution in Southwest China

“…Dadone-Montaudiéet al described one pediatric pigmented DFSP, which was not found to have suspicious transcript even after using RNA sequencing, indicating that a more complicated mechanism might exist (36). There were three cases (present cases 23, 42, and 52) of genetic aberrations in the current study that could not be further identified using NGS because of the poor quality of the specimens, which could be associated with alternative rearrangement (including PDGFD rearrangement and PDGFB rearrangement with novel partner genes), cryptic COL1A1-PDGFB fusion, and even other sophisticated chromosomal aberrations (36, [49][50][51][52]. We still needed more specimens to reveal the genetic characteristics of cryptic pediatric DFSP.…”

Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue

“…TNC is an extracellular matrix protein implicated in guidance of migrating neurons as well as endothelial cells, and in progression of many different types of tumors [39] . Interestingly, it also overexpressed in chondrosarcoma, Ewing sarcoma and dermatofibrosarcoma protuberans and known to promote cancer cell survival and migration as well as metastasis and malignancy therein [40][41][42][43] . Furthermore, TNC has been advocated as a potential target in STS treatment, and TNC specific ligands are available for experimental use [44] .…”

Molecular Characterization of Dermatofibrosarcoma Protuberans

“…Leaving aside a single FS-DFSP recently reported to harbor a novel TNC-PDGFD fusion,22 we combined 22 PDGFD -rearranged DFSPs (14 published; 8 current) with known fusion partners and found that difference in 5′ partner genes might account for their clinicopathologic variations (Table 4). The major COL6A3-PDGFD fusion had a striking predominance in the trunk of females (14/16, 88%), especially the breast (7, 44%) 12,13 .…”

“…The transformation to the fibrosarcomatous (FS) variant mostly occurs de novo but varies in incidence between 5% and 20% of DFSPs with overtly increased recurrent and metastatic rates. [4][5][6] More than 90% of DFSPs harbor an unbalanced t (17;22)(q22;q13) translocation in the form of supernumerary ring chromosome or linear translocation der (22), creating the chimeric fusion of collagen type I alpha 1 chain (COL1A1) and platelet-derived growth factor subunit B (PDGFB) gene. [7][8][9] COL1A1-PDGFB fusion is formed by 5′-COL1A1 with highly variable breakpoints and 3′-PDGFB with a constant breakpoint in exon 2, resulting in a strong swapped COL1A1 promoter that upregulates expression and signaling of PDGFB in an autocrine loop.…”