Dermatofibrosarcoma Protuberans-Like Tumor With COL1A1 Copy Number Gain in the Absence of t(17;22)

Abstract

A 57 year-old woman presented with a three year history of a progressive firm plaque on the right cheek. Skin biopsies revealed a bland, storiform, spindle cell proliferation involving the deep dermis and subcutaneous fat. By immunohistochemistry the tumor cells were diffusely positive for CD34 and caldesmon with multifocal reactivity for EMA and focal, weak staining for SMA. Retinoblastoma protein expression was not detectable in tumor cells by immunohistochemistry. An interphase FISH analysis for PDGFB gene rearrangement was negative. A SNP-array study detected 1) a gain of chromosome segment 17q21.33-q25.3 which overlapped the entire COL1A1 gene with a breakpoint at 17q21.33, approximately 250 Kb centromeric to the 3′ end of COL1A1 gene, 2) several segmental gains on chromosome 11 and 3) an RB1 gene locus with normal copy number and allele frequency. While the current case resembles DFSP, it is unique in that it demonstrates a copy number gain of chromosome 17q in the absence of fusion of COL1A1 and PDGFB genes and an unusual immunohistochemical staining profile. The morphologic and molecular findings suggest a novel molecular variant of DFSP not detectable with standard FISH for PDGFB rearrangement. This variant appears to respond to imatinib after 9 months of follow-up.

Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without PDGFB fusions

“…Altogether, routine molecular screening remains negative in approximately 4% of otherwise typical dermatofibrosarcomas protuberans, raising clinical uncertainties and leading to render a diagnosis of dermatofibrosarcoma protuberans 5 lacking the canonical translocation and therefore "molecularly unconfirmed" (5). Single reports of molecular variants of dermatofibrosarcoma protuberans have been reported but no systematic study has been performed so far (10)(11)(12)(13).…”

Dermatofibrosarcoma protuberans of the face: A clinicopathologic and molecular study of 34 cases

“…A simple summary of clinicopathological information in all 851 DFSPs is shown in Table 2. A review of 72 DFSPs on the face is shown in Table S4 (online Supplement Information) [11,12,17,18]. All 34 patients in our study were adults.…”

“…Besides, Karanian et al [21] described a large group of patients and found that approximately 4 % of typical DFSP remained negative for COL1A1-PDGFB fusion rearrangement in routine molecular screening, consistent with those in our series (5.9 %). In addition, a recent series emphasized that COL1A1-PDGFB fusions and PDGFB rearrangement could be cytogenetically cryptic on FISH [18,22]. Thus, further detection, such as COL1A1 FISH and/or NGS, is needed to enrich the genetic spectrum.…”

Dermatofibrosarcoma protuberans im Gesicht: Klinisch‐pathologische und molekulare Studie mit 34 Fällen

“…Tabelle 2 zeigt einen kurzen Überblick der klinisch-pathologischen Eigenschaften sämtlicher 851 Fälle von DFSP. Tabelle S4 (Online-Supplement) enthält einen Überblick über insgesamt 72 Fälle von fazialen DFSP [11,12,17,18]. Alle In unserer Studie waren die meisten Tumore an Stirn oder Wangen lokalisiert (26/34; 76,5 %).…”