Yonago Acta medica 2014;57:117–118

Short Communication

Epithelial Stem Cells of the Skin Contribute to the Histopathologic Umbrella-likeAppearance in Actinic Keratosis
Motoyuki Mihara
Mihara Dermatology Clinic, Tottori University, 1933-1 Takao, Niimi 718-0003, Japan

ABSTRACT
Although the histopathologic umbrella-like appearanceof the epidermis in actinic keratosis (AK) is well known,
its histopathogenesis has remained unknown. The author
suggests that the penetration depth of ultraviolet B (UVB)
radiation can account for such a histopathologic feature
by affecting specific epidermal stem cell pools, as thestem cells in the epidermis and the bulge stem cells andsebocyte stem cells in the mid-dermis reside at different
depths.

atakatak

Key words

actinic keratosis; buldge stem cell; epidermal stem cell; sebocyte stem cell; ultraviolet B
Hyperplastic/hyperkeratotic actinic keratosis is a frequently encountered subtype of actinic keratosis. Its
defining histopathologic feature is the extension of theuninvolved hyperplastic epithelium of the follicular ostia
and sweat gland orifices over the dysplastic epithelia of
AK in an umbrella-like fashion. This histopathologic
feature has been well known as the Freudenthal funnel
since it was described by Freudenthal 1 in 1926, but its
histopathogenesis has remained unclear to date. The author suggests that this unknown histopathogenesis may
be explained by the different resident locations of theepithelial stem cell populations of the skin.

Fig. 1. Umbrella-like appearance in actinic keratosis (AK). The
border between acrotrichial cells (at) and dysplastic epithelial cellsof actinic keratosis (ak) is sharply defined (hematoxylin and eosinstain). Bar = 50 µm.

guishable from the surrounding epidermal cells undernormal conditions, while their border is sharply definedin AK (Fig. 1), resulting in the characteristic umbrellalike appearance.
AK is a precancerous lesion usually related to sunexposure. UV exposure is the most harmful agent contributing to sunlight-induced carcinogenesis. In the UVrays from sunlight, approximately 95% of the UV radiation that reaches the Earth’s surface is UVA (wavelengthof 320–400 nm), and approximately 5% of it is UVB(wavelength of 290–320 nm).3 However, UVA is poorly
absorbed by DNA, while UVB is readily absorbed byDNA.4 Therefore, UVB more effectively causes DNA
damage and photocarcinogenesis. For UVB to perform
its biological action, it must penetrate to the appropriate
level in the skin. UVB can penetrate the skin to the upper dermis.3 At this depth, UVB is able to influence epidermal stem cells, but cannot influence the bulge stem
cells in the hair follicle bulge and sebocyte stem cells inthe base of sebaceous glands, because the resident locations of these stem cells are definitively in the mid-dermis. As a result, they escape UVB-induced DNA damage and maintain normal conditions. Such a pathologic

REPORT
The epithelial component of the epidermis consistsof epidermal cells and appendageal cells, including
acrotrichial cells and acrosyringeal cells. Pinkus andMehregan2 proposed a theory termed epidermal symbiosis. According to the theory, the epidermal cells and theappendageal cells maintain homeostasis by mitotic division of their own germinal cells, and they may independently act and react under pathologic conditions. Thus,
AK may be considered to be a pathologic condition inwhich the interrelationship between the epidermal cells
and the appendageal cells is disorganised. As described
previously,2 the acrotrichial cells are essentially indistinCorresponding author: Emeritus Professor Motoyuki Mihara, MD
motoyuki@mountain.ocn.ne.jp
Received 2014 June 26
Accepted 2014 July 9
Abbreviation: AK, actinic keratosis

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M. Mihara
The author declares no conflict of interest.

phenomenon may generate an umbrella-like appearance
in the epidermis.
Eccrine gland stem cells were recently identified insweat glands and ducts in the mouse.5 However, to myknowledge, there has not been a report defining the resident location of eccrine gland stem cells in normal human skin. Thus, there is a possibility that eccrine glandstem cells reside much deeper in the dermis than thehair follicle bulge.
In conlusion, UVB can penetrate the skin to theupper dermis. Therefore, epidermal stem cell DNA isalways susceptible to UVB-induced damage from sunlight, while the DNA of bulge stem cells and sebocyte
stem cells is protected from UVB damage because thesestem cells reside deeper, in the mid-dermis. Histopathogenetically, the umbrella-like appearance of AK epidermis may support such a pathologic phenomenon.

References
1 Freudenthal W. Verruca senilis und Keratoma senile. Arch
Dermatol Syph. 1926;152:505-8.
2 Pinkus H, Mehregan AH. A guide to dermatohistopathology.
New York: Appleton-Century-Crofts. Educational Division.
Meredith Corporation; 1969. p. 20-2.
3 Kochevar IE, Taylor CR, Krutuman J. Fundamentals of cutaneous photobiology and photoimmunology. In: Goldsmith
L, Katz SI, Gilchrest BA, Paiier AS, Leffell DJ, Wolff K, eds.
Fitzpatrick’s Dermatology in General Medicine. 8th ed. Volume 1. Chapter 90. New York: McGraw Hill Medical; 2012. p.
1031-48.
4 Kawasumi M, Nghiem P. Ultraviolet radiation carcinogenesis.
In: Goldsmith L, Katz SI, Gilchrest BA, Paiier AS, Leffell DJ,Wolff K, eds. Fitzpatrick’s Dermatology in General Medicine.
8th ed. Volume 1. Chapter 112. New York: McGraw HillMedical; 2012. p. 1251-60.
5 Lu CP, Polak L, Rocha AS, Pasolli HA, Chen SC, Sharma N,et al. Identification of stem cell populations in sweat glands
and ducts reveals roles in homeostasis and wound repair. Cell.
2012;150:136-50. PMID: 22770217.

The main point of this paper was published in Nishinihon Hifuka
2014;76:52 (Japanese), in which the figure and the references were
not attached.

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