Keratoacanthoma and Keratoacanthoma-Like Squamous Cell Carcinoma: Similar Morphology but Different Pathogenesis

Abstract

Differential diagnosis between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is difficult due to their similarities. The mechanisms that drive their distinct biological behavior are poorly understood. To investigate whether the assessment of microvessel density (MVD) could be helpful in KA and SCC differential diagnosis and to gain insight into the pathogenesis of KA-like neoplasms, we compared the density of CD105- and CD34-stained vessels in KAs and SCCs and their relation to the expression of the p53 oncoprotein and proliferation marker Ki67. This is an observational retrospective cohort study. Forty lesions with clinical appearance of KAs (29 KAs and 11 SCCs) entered the study. A biopsy was taken from each lesion at presentation and the natural clinical course was monitored for at least 1 month. Growing or minimally regressing lesions were submitted to complete surgical excision. The diagnoses were established on combined clinical, histological, and follow-up evaluations. The MVD and p53 or Ki67 expression in neoplastic cells were assessed through morphometry. The MVD did not show discriminating power between KAs and SCCs. The Ki67 proliferation rate was significantly higher in SCCs. Although neoangiogenesis (CD105-MVD) in KAs was associated with cell proliferation, in SCCs it was not. There was significant correlation between p53 expression and neoplasia size in SCCs but not in KAs. From our results, we may conclude that KA and SCC have similarities, as CD105- and CD34-MVD. However, the low Ki67 proliferation index and the positive correlation between Ki-67 index and neovascularization in KA suggest a dependence in neovascularization to grow in KA, pointing to involvement of distinct pathogenesis.

FIGURE 1

Immunostaining of microvessels using CD105 in KA (A) and SCC (B). CD34 membrane staining of endothelial cells in KA (C) and SCC (D). Original magnification: ×400.

FIGURE 2

Diffuse nuclear p53 immunostaining in KA (A) and SCC (B); Ki67 immunostaining in KA (C) and SCC (D). Original magnification: ×400.

FIGURE 3

Expression of Ki67, p53, CD34, and CD105 in keratoacanthomas and squamous cell carcinomas. There were no significant differences between KAs and SCCs regarding the CD34 or CD105 microvessel density nor the p53⁺ cells density. The Ki67 staining index was significantly higher in SCCs.

FIGURE 4

Significant positive correlation of MVD-CD105 and Ki67-proliferation index in KAs (A). This was not the case for SCCs (B).

FIGURE 5

Significant positive correlation between the neoplasma size and p53 index (A) and neoplasm size and age in SCC (B).