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Skin - Hyperkeratosis

Image of hyperkeratosis in the skin from a male F344/N rat in a subchronic study
Hyperkeratosis-parakeratotic hyperkeratosis (arrow) in a male F344/N rat from a subchronic study.
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Image of hyperkeratosis in the skin from a female B6C3F1 mouse in a chronic study
Hyperkeratosis-orthokeratotic hyperkeratosis (arrow) in a female B6C3F1 mouse from a chronic study.
Figure 2 of 2
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Hyperkeratosis is most commonly observed in dermal application studies and is often accompanied by or secondary to epithelial hyperplasia. It is characterized by thickening of the stratum corneum ( Figure 1image opens in a pop-up window and Figure 2image opens in a pop-up window ). Hyperkeratosis is most commonly orthokeratotic (thickening of the cornified layer without retained nuclei;  Figure 2image opens in a pop-up window ). Parakeratotic hyperkeratosis, which is characterized by the presence of nuclei in the cornified layer, occurs rarely and is usually concurrent with epithelial hyperplasia ( Figure 1image opens in a pop-up window ).


Whenever present, hyperkeratosis should be recorded and assigned a severity grade. Since parakeratosis is simply a form of hyperkeratosis, only the term “hyperkeratosis” should be used in NTP studies. However, the hyperkeratosis should be described in the pathology narrative as being orthokeratotic or parakeratotic. Associated lesions, such as epithelial hyperplasia and inflammation, should be diagnosed separately.


Peckham JC, Heider K. 1999. Skin and subcutis. In: Pathology of the Mouse: Reference and Atlas (Maronpot RR, Boorman GA, Gaul BW, eds). Cache River Press, Vienna, IL, 555-612.

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.