Clinical, Dermoscopic, and Molecular Features of Acantholytic Squamous Cell Carcinoma: A Systematic Review

Introduction: Acantholytic squamous cell carcinoma (aSCC) is a rare clinicopathological subtype of cutaneous squamous cell carcinoma, accounting for approximately 4.9% of all SCC cases. However, there are currently no standardized criteria for the diagnosis of aSCC. This systematic review is the first to summarize the clinical and molecular features of aSCC.

Methods: A systematic search of Medline, Embase, Scopus, and PubMed was performed. All articles in English or French were included, with no restriction of publication date. All articles with original data pertaining to clinical or molecular characteristics of aSCC were included. Two reviewers screened articles and resolved conflicts.

Results: Our systematic review included 52 studies on the clinical and molecular features of aSCC, including a total of 482 patients (76% male, mean age at diagnosis 68.9 years): 430 cases assessed clinical features, while 149 cases assessed molecular features. The most common location of aSCC was the head and neck (n = 329/430; 76.5%). In terms of morphology, most lesions were described as nodules (n = 93/430, 21.6%), with common surface changes being hyperkeratosis (n = 6), erosion (n = 6), ulceration (n = 5), and crusting (n = 3). With regard to dermoscopy, only six cases were noted in the literature, including findings such as ulceration (n = 3), keratin clots (n = 2), and erosions (n = 2). Thirty-four studies discussed the molecular markers of aSCC, with the most prevalent markers being cytokeratins. CD15 negativity was noted in 23 cases, while common endothelial vascular markers such as CD34 (n = 16), CD31 (n = 15), factor VIII-related antigen (n = 10), and ERG (n = 1) were often not expressed. Finally, expression of intracellular adhesion molecules (i.e., E-cadherin, CD138) was markedly decreased compared to non-acantholytic invasive SCC.

Conclusions: This systematic review summarizes the clinical characteristics and molecular features of aSCC. As clinical differentiation can be difficult, clinicopathological correlation with molecular markers may help ensure proper diagnosis.