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Review
. 2025 May 27;17(11):1785.
doi: 10.3390/cancers17111785.

Molecular Characterization of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma

Jason C Klein  1   2 , Breelyn A Wilky  3 , Heide L Ford  4
Affiliations
Review

Molecular Characterization of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma

Jason C Klein et al. Cancers (Basel). .

Abstract

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are dermal-based sarcomas that fall along a spectrum with different rates of local recurrence and metastasis. While AFX is less aggressive and confined to the dermis, PDS invades the subcutis. These tumors are most likely of mesenchymal origin, although they share common mutations with undifferentiated squamous cell carcinoma. Due to the rarity of these tumors, few studies have examined their molecular composition and gene expression. Initial studies, including exome and bulk RNA sequencing, targeted DNA sequencing of gene panels, DNA methylation, and copy number analyses, have identified recurrent UV-induced mutations in TP53, NOTCH, CDKN2A, and the TERT promoter. Recently, the first scRNA-seq dataset in AFX and PDS identified COL6A3 as a novel biomarker. In this review, we synthesize the above datasets and discuss our current understanding of the molecular drivers and prognostic biomarkers in these tumors.

Keywords: atypical fibroxanthoma; genetics; pleomorphic dermal sarcoma; soft tissue sarcoma; undifferentiated pleomorphic sarcoma.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Diseases associated with frequently mutated genes in AFX and PDS. Blue text for disease indicates cancer.
See this image and copyright information in PMC

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