Atypical fibroxanthoma and pleomorphic dermal sarcoma - gene expression analysis compared with undifferentiated cutaneous squamous cell carcinoma

Background: The histogenetic origin of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) has not been definitively elucidated. In addition to a fibroblastic origin, a keratinocytic differentiation is discussed due to strong clinical, histomorphological and molecular genetic similarities with undifferentiated cutaneous squamous cell carcinoma (cSCC). Patients and Methods: 56 cases (36 AFXs, 8 PDSs, 12 undifferentiated cSCCs) were evaluated for their clinical, histomorphological, and immunohistochemical characteristics. RNA transcriptome analysis was performed on 18 cases (6 AFXs/PDSs, 6 undifferentiated cSCCs, 6 differentiated cSCCs). Results: Clinically, the strong similarities in age, gender and tumor location were confirmed. Without further immunohistochemical staining, histomorphological differentiation between AFX/PDS and undifferentiated cSCC is often impossible. Principal component analysis of the RNA transcriptome analysis showed that AFX/PDS and differentiated cSCC each formed their own cluster, while the undifferentiated cSCCs fall in between these two groups, but without forming a cluster of their own. When examining differentially expressed genes (DEGs), the heat maps showed that there were cases within the undifferentiated cSCC that were more likely to be AFX/PDS than differentiated cSCC based on their expression profile. Conclusions: The results provide evidence of molecular similarities between AFX/PDS and undifferentiated cSCC and suggest a common histogenetic origin.