Differentiating keratoacanthoma from squamous cell carcinoma by the use of apoptotic and cell adhesion markers

Aims : Keratoacanthomas (KA) are well-differentiated squamoproliferative skin lesions that grow rapidly and regress spontaneously. In contrast, squamous cell carcinomas (SCC) can have variable differentiation, inexorably progress and on occasion metastasize. Distinguishing between KA and SCC using haematoxylin and eosin-stained sections from an initial biopsy can often be difficult. There is also some debate as to whether KA is simply a variety of well-differentiated SCC or a distinct entity. Methods and results : Initial biopsy sections from 25 cases of SCC and 20 of KA were labelled with markers for both the initiation (the cytolytic receptor P2X7) and end-stage (terminal deoxynucleotidyl transferase biotin–dUTP nick end labelling) of apoptosis, telomerase-associated protein (TP1) and the cell adhesion protein E-cadherin. As this was a retrospective study, the clinical outcome of each case was known. This resulted in a unique labelling pattern of each marker for SCC and KA, allowing a differential diagnosis between the two conditions. The simplest marker to use for this purpose was anti-P2X7. Sections from five cases that were initially very difficult to diagnose were correctly identified as SCC using this method. Conclusions : These results support the view that KA has a different pathogenesis and biochemistry from that of SCC, and is a distinct entity. Anti-P2X7 labelling, using routine immunohistochemical techniques, provides a method for differentially diagnosing these conditions.