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Diseases 2014, 2(2), 106-119; doi:10.3390/diseases2020106

Keratoacanthoma Pathobiology in Mouse Models

1,* , 2, 1, 3 and 1
1 Department of Pathology, University of Iowa, Iowa City, IA 52242, USA 2 Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA 3 Department of Anatomy & Cell Biology, Roy J. & Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
* Author to whom correspondence should be addressed.
Received: 25 March 2014 / Revised: 16 May 2014 / Accepted: 19 May 2014 / Published: 23 May 2014
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Recently we described skin tumors driven by skin-specific expression of Zmiz1 and here we define keratoacanthoma pathobiology in this mouse model. Similar to human keratoacanthoma development, we were able to segregate murine keratoacanthomas into three developmental phases: growth, maturation, and regression. These tumors had areas with cellular atypia, high mitotic rate, and minor local invasion in the growth phase, but with development they transitioned to maturation and regression phases with evidence of resolution. The early aggressive appearance could easily be misdiagnosed as a malignant change if the natural pathobiology was not well-defined in the model. To corroborate these findings in the Zmiz1 model, we examined squamous skin tumors from another tumor study in aging mice, and these tumors followed a similar biological progression. Lastly, we were able to evaluate the utility of the model to assess immune cell infiltration (F4/80, B220 Granzyme B, CD3 cells, arginase-1) in the regression phase; however, because inflammation was present at all phases of development, a more comprehensive approach will be needed in future investigations. Our study of keratoacanthomas in selected murine models suggests that these squamous tumors can appear histologically aggressive during early development, but with time will enter a regression phase indicating a benign biology. Importantly, studies of squamous skin tumor models should be cautious in tumor diagnosis as the early growth distinction between malignant versus benign based solely on histopathology may not be easily discerned without longitudinal studies to confirm the tumor pathobiology.
Keywords: keratoacanthoma; mouse models; histopathology; regression keratoacanthoma; mouse models; histopathology; regression
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Gibson-Corley, K.N.; Rogers, L.M.; Goeken, A.; Dupuy, A.J.; Meyerholz, D.K. Keratoacanthoma Pathobiology in Mouse Models. Diseases 2014, 2, 106-119.

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