A Clinical and Biological Review of Keratoacanthoma

A. Tisack; A. Fotouhi; C. Fidai; B.J. Friedman; D. Ozog; J. Veenstra


The British Journal of Dermatology. 2021;185(3):487-498. 

In This Article


Current research has led to improved understanding of KA and cSCC but has yet to elucidate a reliable set of criteria to discriminate between them. However, several morphological, biological, molecular and immunological characteristics have begun to separate KA from the cSCC spectrum, suggesting a separate, but related, benign entity (Figure 2). Recent investigation of the Wnt and retinoic acid pathways has led to new insights into the development paradigm of KAs, which has helped better distinguish them from cSCC. This, in conjunction with the differential immune reactivity and response to immune checkpoint inhibitors, suggests discordance in the pathways that lead to cSCC and KA development.

Identifying reliable markers to differentiate malignant cSCC from benign and reactive squamoproliferative lesions, such as KA, is crucial to avoid overtreatment and provide a wider degree of flexibility in treatment than those recommended strictly for cSCC. Definitive removal of cSCC is necessary due to the malignant potential these tumours possess; however, that does not appear to be the case with KAs, where noninvasive treatment options can be highly successful.[97,100] Additionally, new insights generated from Wnt pathway blockade suggest that retinoids offer a viable treatment approach.[57] Clearly, KAs possess different molecular drivers, immune infiltrates and phases of evolution, which may be targeted with a unique therapeutic approach.

Further investigation is needed to reliably discriminate KA from cSCC to better inform patient prognosis, guide clinical management, and optimize outcomes. Whole-genome or total RNA sequencing looking beyond coding elements has yet to be performed. While multimodal single-cell analysis of cSCC has recently been undertaken, further single-cell studies of KA in direct comparison with cSCC are required to fully characterize unique cell populations, cellular interactions, and insights into the activation and behavioural status within the tumour microenvironment. This will enable the development of clinically applicable biomarkers for improved tumour characterization to better guide management strategies, encourage the use of less invasive treatments, and decrease surgical morbidity.