Dermatofibrosarcoma protuberans with platelet‐derived growth factor‐D rearrangement; two cases with morphologically distinct presentations

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a mesenchymal neoplasm that is usually located in the dermis or subcutis and is locally aggressive. Rarely, these lesions may undergo fibrosarcomatous transformation, which is thought to increase their metastatic potential. DFSP is classically associated with a 17;22 translocation (or ring chromosome thereof) resulting in fusion of the COL1A1 and PDGFB genes. However, variant fusions involving PDGFD have been recently reported. Herein, we present two morphologically diverse cases of DFSP with PDGFD rearrangement. Case 1 is a 68-year-old female with a left dorsal foot lesion. Morphologically, the lesion is unusual as it is a well-circumscribed, hypercellular, subcutaneous nodule with uniform CD34-positive spindle cells arranged in a herringbone pattern without storiform arrangement or "honeycombing" fat entrapment. It was diagnosed as pure fibrosarcomatous DFSP. Case 2 is a 37-year-old male with a right supra-auricular lesion. Morphologically, the lesion displays classic DFSP features including bland CD34-positive spindle cells with storiform growth, fat entrapment, and infiltrative borders. Both lesions were negative for COL1A1-PDGFB fusion but positive for PDGFD rearrangement by fluorescence in situ hybridization (FISH) analysis. FISH testing for PDGFD rearrangement should be performed in cases where there is a high suspicion for DFSP but initial studies for COL1A1-PDGFB are negative.

Spindle cell neoplasms with novel LTK fusion – Expanding the spectrum of kinase fusion‐positive soft tissue tumors

“…Interestingly, the DNA methylation clustering analysis suggests a closer histogenesis to DFSP, similar to our previously reported case of a primary bone sarcoma with MAP4::RAF1 fusion 15 . DFSP is a locally aggressive fibroblastic neoplasm, having a cellular storiform appearance and carrying a COL1A1::PDGFB fusions 26 or rarely alternative PDGFD rearrangements 27–30 . There are some morphological variants such as pigmented, myxoid, myoid, and fibrosarcomatous variants, 31 but the morphology of the current cases does not fully fit into classical or any of the known specific variant.…”

“…15 DFSP is a locally aggressive fibroblastic neoplasm, having a cellular storiform appearance and carrying a COL1A1::PDGFB fusions 26 or rarely alternative PDGFD rearrangements. [27][28][29][30] There are some morphological variants such as pigmented, myxoid, myoid, and fibrosarcomatous variants, 31 but the morphology of the current cases does not fully fit into classical or any of the known specific variant. The patchy coexpression of CD34 with S100 is also unusual.…”

Platelet-Derived Growth Factor-D Fusion-Positive Dermatofibrosarcoma Protuberans: Case Report of an Atypical Breast Mass and Literature Review

“…11 Thus far, COL6A3, EMILIN2, and TNC have been described as forming fusion products with PDGFD in DFSP. [7][8][9][10]12,15 Table 1 enumerates the 30 PDGFD fusionpositive cases reported in the literature, as well as the case presented here. Two of the cases in Table 1 are found in a retrospective cohort of 16 breast and upper chest DFSPs, resulting in a slight selection bias for breast tumors.…”

“…[6][7][8][9] Less than 10% of DFSP may be negative for the COL1A1::PDGFB fusion, and instead have an atypical fusion such as COL6A3::PDGFD t(2;11), EMILIN2:: PDGFD t(11;18), or TNC::PDGFD t(9;11). 3,[7][8][9][10][11][12] Similar to COL1A1::PDGFB, the COL6A3::PDGFD translocation brings together a different collagen gene (COL6A3, located on chromosome 2q37) and platelet-derived growth factor gene (PDGFD, located on chromosome 11q22) to drive unregulated autocrine expression of platelet-derived growth factor subunit D driven by the highly expressed collagen type IV alpha 3 chain. Unlike PDGFB, the native PDGFD protein has an N-terminal CUB domain, which must be proteolytically cleaved at Arg-247 or Arg-249 by urokinase plasminogen activator before it can stimulate platelet-derived growth factor receptor signaling.…”