Study of Epithelial to Mesenchymal Transition in Atypical Fibroxanthoma and Undifferentiated Pleomorphic Sarcoma to Discern an Epithelial Origin

Abstract

Atypical fibroxanthoma (AFX) is considered a fibroblastic or myofibroblastic neoplasm probably corresponding to a superficial variant of undifferentiated pleomorphic sarcoma (UPS). However, an epithelial origin has also been postulated. An immunohistochemical study of the epithelial to mesenchymal transition (EMT) phenomenon was performed in a series of 19 AFX and 4 UPS to discern an epithelial origin. A panel of epithelial (cytokeratins AE1-AE3 panel, podoplanin D2-40, and E-cadherin) and EMT (vimentin, Twist, Zeb1, and Snail1) markers were evaluated in both tumoral cells and the adjacent epidermis. Podoplanin and Snail1 were negative in all the samples. Nuclear E-cadherin, Twist, and Zeb1 were detected in most lesions, as previously reported in other sarcomas. In the epidermis, E-cadherin showed a normal membranous pattern and only isolated cells were positive for vimentin. Twist and Zeb1 were mainly negative in the epidermis. None of the immunohistochemical markers mentioned above elicited a conspicuous bridging between the epidermis and the dermis. Our findings suggest that EMT does not play a role in the development of AFX or UPS.

Risk factors for local atypical fibroxanthoma recurrence and progression to pleomorphic dermal sarcoma: A meta‐analysis of individualized participant data

“…The differentiation between AFX and PDS is challenging since the tumors resemble each other both histopathologically and immunohistochemically. PDS is distinguished from AFX by features such as histological invasion of the subcutaneous tissue, vascular or perineural invasion, the presence of necrosis or local invasion/metastases 31,32 . The current consensus is that AFX does not metastasize 9,10 ; therefore, we chose to consider the cases of metastasis as a progression of the primary AFX diagnosis to a PDS.…”

Atypical fibroxanthoma and pleomorphic dermal sarcoma: A reappraisal

“…From the immunohistochemical point of view, we did not find a different profile among tumors with different cellular types. Toll and coworkers evaluated the immunohistochemical expression of EMT (epithelial to mesenchymal transition) markers in a series of AFX and PDS, concluding that EMT does not play a role in the development of these tumors 18 . On the contrary, a more recent study found that EMT is upregulated in AFX.…”

Expression of 3q oncogene SEC62 in atypical fibroxanthoma‑immunohistochemical analysis of 41 cases and correlation with clinical, viral and histopathologic features

“…Relationship of AFX and pleomorphic dermal sarcoma (PDS) is still not clearly identified (43). As AFX is a diagnosis of exclusion, it is mandatory to apply strict diagnostic criteria that include diligent immunohistochemical workup (8–12).…”

“…After its first description in 1963, much effort was spent to better understand the tumorigenesis and molecular biology of this tumor entity including immunohistochemical analyses, electron microscopy, comparative genomic hybridization and next generation sequencing (5,6). However, the pathogenesis of AFX is still unclear with keratinocytes, fibroblasts and myofibroblasts having been discussed as potential cells of origin (7,8). Since this tumor shows a highly heterogeneous histological structure with tumor cells ranging from spindle and epithelioid to multinucleated cells and a variably structured extracellular matrix, the histological diagnosis is challenging with undifferentiated pleomorphic sarcoma, malignant fibrous histiocytoma, dedifferentiated squamous cell carcinoma, dermatofibrosarcoma protuberance and leiomyosarcoma as differential diagnoses (1,9).…”

“…Since this tumor shows a highly heterogeneous histological structure with tumor cells ranging from spindle and epithelioid to multinucleated cells and a variably structured extracellular matrix, the histological diagnosis is challenging with undifferentiated pleomorphic sarcoma, malignant fibrous histiocytoma, dedifferentiated squamous cell carcinoma, dermatofibrosarcoma protuberance and leiomyosarcoma as differential diagnoses (1,9). Immunohistochemical markers that can help to differentiate AFX from other tumor entities are CD99, S-100, CD34, cytokeratin, desmin, CD10, vimentin, HMB-45, CD68 and p63 (8–12). However, a disease-specific marker as well as a prognostic marker indicating a higher risk of recurrence or distant metastasis is still missing (1,3,4).…”