Utility of p53 immunohistochemistry in atypical fibroxanthoma and pleomorphic dermal sarcoma: a retrospective study of 50 patients

Background Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are uncommon cutaneous mesenchymal neoplasms with overlapping clinical, histopathological and immunohistochemical features. Although TP53 pathway alterations are well recognized in both tumours, the practical role of p53 immunohistochemistry in routine dermatopathology has not been well established. Objectives To assess the practical value of p53 immunohistochemistry in the routine diagnostic evaluation of AFX and PDS. Methods Patients diagnosed with AFX and PDS over a 5-year period were retrospectively identified from the archives of a single dermatopathology department. Clinical and histopathological data were reviewed. p53 immunohistochemistry, performed as part of routine diagnostic practice, was evaluated and categorized as aberrant overexpression, aberrant null pattern or wildtype expression. Particular attention was given to its contribution in diagnostically challenging settings, including assessment of subtle subcutaneous extension, distinction from histological mimics, evaluation of re-excision specimens and assessment of tumour margins. Results Fifty specimens from 43 patients were included. Patients were predominantly men (86%) with a mean age of 71.7 years, and their tumours arose almost exclusively on chronically sun-exposed skin of the head and neck. Aberrant p53 expression was identified in 46 of 50 specimens (92%), comprising diffuse overexpression in 39 specimens and a null pattern in 7, while 4 specimens demonstrated a wildtype staining pattern. In three re-excision specimens containing residual tumour, p53 staining showed concordance with the corresponding primary lesion and facilitated distinction between residual tumour and reactive stromal changes, aiding in assessment of tumour extent and margin status. p53 also highlighted subtle subcutaneous extension supporting classification as PDS and proved useful in diagnostically challenging spindle-cell proliferations with relatively mild cytological atypia. Conclusions p53 immunohistochemistry is a valuable adjunct in the routine assessment of AFX and PDS. Although it lacks specificity and should not be used as a standalone diagnostic marker, its frequent aberrant expression can assist in highlighting neoplastic cells in diagnostically challenging cases. It is particularly useful in re-excision specimens, assessment of subtle tumour extension and distinction from selected histological mimics when interpreted alongside morphology and an appropriate immunohistochemical panel.