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Fig. 1. Phenotype and histotype of HK1.fos/ ${Delta}$ 5Pten^flx mice. (Top row) RU486-treated homozygous and heterozygous HK1.fos- ${Delta}$ 5Pten^flx mice exhibit ear keratoacanthomas (KAs). Control HK1.fos siblings possess small papillomas and RU486-treated K14.cre/ ${Delta}$ 5Pten^flx mice exhibit hyperkeratosis. Lower panel: (A) RU486-treated HK1.fos skin histology was indistinguishable from normal. (B) K14.cre/ ${Delta}$ 5Pten^flx epidermis exhibits mild hyperplasia, significant hyperkeratosis and ghost cells indicative of incorrect cornification. (C) HK1.fos papilloma histology displays expanded epidermal compartments but an overall ordered keratinocyte differentiation pattern. (D) A composite HK1.fos/ ${Delta}$ 5Pten^flx KA micrograph displays two distinct histotypes: an upper differentiated area of massive keratosis interspaced with fronds of keratinocytes; and a lower hyperproliferative papilloma-like region. (E) HK1.fos/ ${Delta}$ 5Pten^flx KA keratinocytes of differentiated regions display a distinct disorder to the programme of differentiation, with cornified and granular cells co-existing alongside basal layer keratinocytes (arrows). (F) Such regions also exhibited a prominent stratum lucidum (arrows) and (G) premature differentiation gave rise to micro-cysts (arrows). Scale bars: 100 µm in A-C; 50 µm in E-G; $~$ 175 µm in D.

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