What is the pathogenesis of dermatofibrosarcoma protuberans (DFSP)?

Updated: Oct 07, 2019
  • Author: Guy J Petruzzelli, MD, PhD, MBA, FACS; Chief Editor: Gregory Gary Caputy, MD, PhD, FICS  more...
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Answer

Answer

Pathogenesis

Upon histologic examination, DFSP involves the dermis and often the subcutaneous fat. The lesion consists of plump spindle cells, which radiate from a fibrous center to form the characteristic cartwheel or storiform pattern. This characteristic storiform pattern does not occur in DFs. Corresponding clinically to an indolent growth rate, the lesion contains infrequent mitotic figures. The lesion is not as well defined at the margins, with increased collagen deposition that blends in with the normal dermis. Fingerlike projections of this lesion extend into normal tissue, thereby establishing territory in seemingly normal tissue. This extension often creates difficulties in excising the lesion and is the basis for its frequent recurrence.

The cell origin of DFSP remains controversial. Through tissue culture studies, Shindo and colleagues have concluded that the DFSP cells are of histocytic origin. [80] Through electron microscopic studies, other investigators have concluded DFSP cells have characteristics that are more in line with fibroblasts or myofibroblasts. [81, 82]

Although the characteristic cartwheel pattern can be used to distinguish DFSP from DF, cellular DF can appear similar to DFSP, making histologic diagnosis difficult. With the exclusive expression of the hematopoietic progenitor antigen CD-34 in cells from DFSP, immunohistochemistry studies have been used to differentiate DFSP from DF and cellular DF. [83, 84, 85]

In the era of cytogenetics and molecular biology, a characteristic reciprocal translocation, t(17;22)(q22;q13), has been identified for DFSP, [86, 87] creating the fusion of collagen type I alpha 1 (COL1A1) to platelet-derived growth factor beta (PDGFB). [88] This rearrangement fuses the COL1A1 to the PDGFB chain. However, this fusion product may not necessarily be the oncogenic factor responsible for DFSP. This translocation deletes exon 1 of PDGFB, resulting in the elimination of the normal regulation of the PDGFB gene. In addition, the resulting COL1A1/PDGF-B fusion protein is processed and dimerized to become PDGF-BB, which can then act as a ligand to the PDGFB receptor. [89] The combination of dysregulation of the PDGFB gene at the chromosomal locus and at the posttranslational step presumably results in the constitutive activation of the PDGFB receptor, providing autocrine signals for the cells to proliferate.

For diagnostic purposes, Nishio and colleagues used comparative genomic hybridization as a method to distinguish between DF and DFSP, focusing on chromosomes 17 and 22 as critical determinants. [90] However, comparative genomic hybridization is a cumbersome, time-consuming technique and is currently impractical as a clinical diagnostic tool. On a more practical level, other investigators have used reverse transcriptase polymerase chain reaction to amplify and identify the COL1A1-PDGFB fusion product. [88, 91, 92]


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