Actinic Cheilitis: A Case Report and a

Review of the Literature

Neil Hamilton Wooda

Razia Khammissaa
Robin Meyerova
Johan Lemmerb
Liviu Fellera

Abstract
In actinic cheilitis, the current view is that the keratinocytes have undergone transformation
forming a field of epithelium with the potential for neoplastic transformation. Clinical features in-
clude diffuse and poorly demarcated atrophic, erosive or keratotic plaques that may affect some
parts of, or the entire vermilion border. Fair-complexioned people, those with albinism and people
with eversion of the lip are all subject to actinic cheilitis. Prophylactic measures against all forms of
sunlight-induced lesions must include limitation of exposure to the sun during peak sunlight hours,
the use of appropriate protective clothing, and the use of a sunscreen cream. In this article, a case
of albinism is used to illustrate the nature of actinic cheilitis, its clinical features and its treatment.
(Eur J Dent 2011;5:101-106)

Key words: Actinic cheilitis; UVB; Squamous cell carcinoma.

Introduction
Actinic cheilitis is a pathological condition that the upper and lower lips are prominent, as in bi-
most frequently affects the vermilion border of the maxillary protrusion, the upper lip may also be
lower lip.1-3 In persons with everted lower lips, as more vulnerable to sunlight exposure. In the past,
a racial characteristic or as an inherited trait, the actinic cheilitis was regarded as being potentially
mucosal surface of the lower lip, which is partly malignant, with not infrequent transformation into
exposed to sunlight, is also affected. When both invasive, metastasizing squamous cell carcinoma.
An alternative view states that the keratino-
a
Department of Periodontology & Oral Medicine, cytes in actinic cheilitis have already undergone
University of Limpopo, Medunsa Campus, South Africa. ultraviolet light-induced molecular and genetic
b
Honorary Professor, Department of Periodontology &
transformation into neoplastic keratinocytes, that
Oral Medicine, University of Limpopo, Medunsa
Campus; and Professor Emeritus of Oral Medicine and actinic cheilitis is in fact the result of clonal expan-
Periodontology, University of the Witwatersrand, sion of the transformed keratinocytes,3-7 and that
Johannesburg, South Africa. it should be considered from its initiation to be an
in-situ squamous cell carcinoma.8
Corresponding author: Neil Hamilton Wood
Department of Periodontology and Oral Medicine, The affected person complains of an inelas-
Box D26, School of Dentistry, Faculty of Health Sciences, tic or tight sensation in the lip. On examination
University of Limpopo, Medunsa 0204, South Africa. one finds mottling of the lip with atrophic areas or
Phone: (012) 5214834
Fax: (012) 5214835
shallow erosions and rough, scaly, flaky keratotic
E-mail: [email protected] patches on some parts, or on the entire exposed

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Actinic cheilitis

portion of the lip and sometimes with small wrin- vermilionectomy showed areas of severe dysplasia
kles in the vermilion border.2,3 When the surface and severe basophilic degeneration. There was no
of the lesion is palpated, there is a fine sandpaper- evidence of in-situ squamous cell carcinoma or in-
like feeling.2 The keratotic patches progress to pal- vasive squamous cell carcinoma. The patient was
pable thickening and induration, and eventually one given advice about sunlight protection. The healing
or more of them may become clearly demarcated was uneventful (Figure 3). The patient had slight
or may ulcerate. Such changes are suggestive of chronic periodontitis, which was treated.
invasive squamous cell carcinoma.2,3,7,9
Histopathological changes in actinic cheilitis DISCUSSION
range from atrophy to hyperplasia of the squamous The wavelength of ultraviolet (UV) light lies
cell epithelium of the vermilion border, with varying within the range of 100-400 nm (1 nm = 10-9 m) of
degrees of keratinisation, disordered maturation, the electromagnetic spectrum. UV light is classi-
increased mitotic activity and cytological atypia. fied as UV-A, -B and -C. UVC is in the range of 100-
Drop-shaped epithelial pegs are often present, but 290 nm; UVB, 290-320 nm; and UVA, about 320-400
the basement membrane is intact. The underlying nm. Sunlight UVC is almost completely filtered out
connective tissue shows basophilic degeneration by the atmosphere. Both UVA and UVB can con-
(solar elastosis).7,10 Based on the above-mentioned tribute to ageing of the skin by damaging collagen,
microscopic changes, actinic cheilitis should be re- breaking down vitamin A,11 by causing local immu-
garded as an intra-epithelial, or in-situ neoplasm.3,8 nosuppression12 and by ionisation, which releases
Anyone who has suffered excessive exposure to hydroxyl and oxygen radicals and thus contributes
the sun can develop actinic cheilitis, but fair-com- indirectly to DNA damage. UVB from the sun, which
plexioned people, especially people affected with is only partly filtered out by the atmosphere, can
albinism, are particularly at risk.8 cause mutagenic changes; a common event of this
kind is the formation of aberrant covalent bonds
CASE REPORT between adjacent cytosine bases in epithelial DNA.
A 35-year-old black female with type 1 oculocuta- Cells with these dimers of cytosine in their DNA
neous albinism and multiple basal cell carcinomas then propagate, giving rise to clones of mutated
of the face (Figure 1) was referred for diagnosis and cells.
treatment of lesions of the vermilion borders of the Actinic keratosis of the skin is thus a primar-
lips (Figure 2), which were of six months duration. ily UVB-induced intra-epithelial neoplasm: the
The patient reported that her basal cell carcinomas analogous lesion of the vermilion border of the lip
had been diagnosed two years previously and had is called actinic cheilitis.13 In the initiation stage of
been treated with topical 5-fluorouracil, but with actinic-induced carcinogenesis following signifi-
only partial success. She was still attending at the cant exposure to the sun, UVB causes mutations
dermatology clinic. Apart from the oculocutaneous in the epithelial p53 tumour-suppressor gene that
albinism and the facial basal cell carcinomas, the result in the dysregulation of its functions.6
patient claimed to be healthy. There were multiple If there is only limited exposure to UVB, p53 can
irregular, rough, scaly macules on the vermilion retain sufficient functionality to arrest the cell cycle,
borders of both the upper and lower lips, extending permitting activation of repair processes of cellular
beyond the vermilion-cutaneous margins in places, DNA before the cell enters the phase of DNA syn-
and both lips were swollen and painful (Figure 2). thesis. A cell with repaired DNA can then proceed
Microscopic examination of two incisional biopsy through the rest of the cell cycle to cell division.
specimens showed epithelial changes of hyperker- Very severe UVB exposure, in contrast, can dam-
atosis, acanthosis, dyskeratosis and moderate dys- age the DNA sufficiently to render it beyond repair,
plasia, with a dense chronic inflammatory infiltrate and p53 then activates cellular pathways leading to
and basophilic degeneration of the lamina propria. programmed cell death (apoptosis) (Figure 4).14
The diagnosis was actinic cheilitis. UVB-induced dysregulation of the function of
In view of the extent of the lip lesions, it was de- the tumour-suppressor gene p53 results in ge-
cided to treat both upper and lower lips surgically. nomic instability, making the cells susceptible to
Microscopic examination of the tissue removed by further critical UVB-induced genetic alterations

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 Wood, Khammissa, Meyerov, Lemmer, Feller

with ultimate malignant transformation of the af- and infection of the lip by the human papillomavi-
fected cells (Figure 4).6,15 It is evident that UVB is rus may cause additional cytogenetic alterations
a complete carcinogen since it not only initiates and further increase the risk of actinic cheilitis be-
the genetic alteration of epithelial cells but also coming carcinomatous.13
subsequently promotes the expansion of clones Oculocutaneous albinism (OCA) encompasses
of transformed cells, which then display all the a heterogeneous group of four genetically inher-
characteristics of malignancy.6,16 Actinic keratosis ited autosomal recessive conditions characterised
and actinic cheilitis occur more frequently in pale by hypopigmentation of the skin, hair and eyes
people, particularly in those with fair complexions, brought about by a complete or partial reduction
persons with albinism, males, the elderly, those in melanin biosynthesis. At least four defective
who live at high altitudes or close to the equator, genes are associated with OCA, and they cause
and of course, those who by reason of their oc- OCA types 1, 2, 3, and 4.17 OCA type 1, the most
cupations or their leisure activities have excessive common type of albinism worldwide, results from
exposure to the sun.6,8 a genetic absence of tyrosinase, which is an es-
The vermilion border of the lower lip may also sential enzyme necessary for melanin produc-
be more vulnerable to sunlight-induced lesions tion.18 In OCA type 2, the most common type of
because its epithelium is thin, has a thin keratin albinism in black people in Africa, there is some
layer and has a lower melanin content.2 Smoking degree of tyrosinase activity and melanin produc-
tion.17 Black persons with OCA type 2 have pale
skin, sandy-coloured hair and light-brown or blue
irises.19
As melanin protects the basal (progenitor)
layer of keratinocytes from solar energy, persons
with relatively few granules of melanin in their ke-
ratinocytes, especially those with OCA, are more
likely to develop non-malignant and malignant
actinic skin lesions, including sunburns, blisters,
solar elastosis and lentigenes, and squamous and
basal cell carcinomas.19
It has been reported that in Africa, black per-
sons with albinism are often exposed to social dis-
crimination as a result of superstitious beliefs.19,20
As a result of the stigma attached to albinism,
Figure 1. Multiple basal cell carcinomas of the face (arrows).

Figure 2. Actinic cheilitis of the upper and lower lips. Incisional biopsies were taken Figure 3. The lips 4 weeks after treatment.
from the areas marked as X and Y. The arrows show the extension of the lesions
beyond the vermilion-cutaneous margins.

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Actinic cheilitis

Figure 4. Schematic representation of UV-B induced carcinogenesis.

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 Wood, Khammissa, Meyerov, Lemmer, Feller

black persons with albinism may be shunned by introduced in childhood and continued throughout
their communities and may delay seeking medi- life. The basic precautions are: avoidance of out-
cal treatment until late in the course of any ac- door activities during peak sunlight hours; wear-
tinic lesion, most importantly carcinoma.19 Our ing of protective clothing that covers as much of
patient with albinism was in fact well integrated the skin as the outdoor activity will allow and of a
in her community, was an office worker, and was wide-brimmed hat for the face and lips; and the
not occupationally exposed to the sun. As is typical liberal and frequent use of an effective sunscreen
for persons with albinism, our patient had actinic preparation.1,16,24
cheilitis and multiple basal cell carcinomas. Be-
cause albinism itself is not a premalignant condi- CONCLUSIONS
tion, her actinic skin lesions must have resulted Actinic cheilitis is the result of clonal expan-
from the fact that in the part of South Africa where sion of UVB-induced transformed keratinocytes
she lives, there has been on average in the past 2 characterised by molecular and genomic altera-
years, 8.55 hours of sunlight per day and the alti- tions causing genomic instability. Additional UVB-
tude is 1306 meters above sea level, so substantial induced genetic changes are necessary for full
exposure to the sun is inescapable.21 malignant transformation with the potential for
Actinic cheilitis may show epithelial changes invasiveness and metastasis.
of simple keratosis, different grades of epithe- Prevention of actinic cheilitis can be achieved
lial dysplasia, in-situ carcinoma or even invasive by reducing cumulative exposure to UVB radia-
squamous cell carcinoma, all of which at some tion. The use of protective clothing, reduced out-
stage may have similar clinical appearances.2,3 It door activities, and the use of sunscreens should
cannot be predicted whether or when actinic chei- be introduced early in childhood and continued
litis will progress to squamous cell carcinoma. throughout life.
Consequently, a clinical diagnosis of actinic chei-
litis must always be supported by histopathologi- REFERENCES
cal evidence, but a single biopsy result may not 1. Schwartz RA, Bridges TM, Butani AK, Ehrlich A. Actinic
be conclusive, and the prudent clinician would be keratoses: an occupational and environmental disorder.
well advised to take a biopsy from more than one Eur Acad Dermatol Venerol 2008;22:606-615.
site.3,22 2. Markopoulos A, Albanidou-Farmaki E, Kayavis I. Actinic
Indeed, in some cases, surgical excision of the chelitis: clinical and pathologic characteristics in 65 cases.
entire vermilion border (vermilionectomy) with Oral Dis 2004;10:212-216.
histological examination of serial sections is the 3. Nico MMS, Rivitti EA, Laurenco SV. Actinic chelitis: his-
preferred treatment.3 Other possible treatment tologic study of the entire vermilion and comparison with
modalities include electrodessication, cryosur- previous biopsy. J Cutan Pathol 2007;34:309-314.
gery, laser treatment, photodynamic therapy, or 4. Rewert-Huber J, Stockfleth E, Kerl H. Pathology and
topical treatment with the antineoplastic agent pathobiology of actinic (solar) keratosis an update. Br J
5-fluorouracil or the immunomodulator imiqui- Dermatol 2007;157(suppl 2):18-20.
mod; however, with these modalities, the tissue is 5. Ackerman AB, Mones JM. Solar (actinic) keratosis in squa-
not available for histological examination.1,2,8,9,23,24 mous cell carcinoma. Br J Dermatol 2006;155:9-22.
It has recently been reported that photodynam- 6. Bickers DR. Photosensitivity and other reactants to light.
ic therapy using the methyl-ester of aminolevulin- In: Kasper DL et al., eds. Harrisons Principles of Internal
ic acid as a photosensitising agent is a very effec- Medicine. 16thed. New York: McGraw-Hill; 2005:324-329.
tive treatment modality for actinic cheilitis. It is 7. Cockerell CJ. Pathology and pathobiology of the actinic
well tolerated by patients and provides excellent (solar) keratosis. Br J Dermatol 2003;149(suppl 66):34-36.
cosmetic outcomes.23 8. Rossi R, Mor M, Lott T. Actinic keratosis. Int J Dermatol
Regardless of the treatment modality used for 2007;46:895-904.
actinic cheilitis, regular clinical follow-up is es- 9. Holmes C, Foley P, Freeman M, Chong AH. Solar keratosis:
sential.5 Protection against the potentially damag- Epidemiology, pathogenesis, presentation and treatment.
ing effects of sunlight exposure depends upon tak- Australas J Dermatol 2007;48:67-76.
ing a few straightforward precautions that must be

January 2011 - Vol.5 European Journal of Dentistry

105
Actinic cheilitis

10. Neto Pimentel DR, Michalany N, Alchorne M, Abreu M,

Borra RC, Weckx L. Actinic cheilitis: histopathology and
p53. J Cutan Pathol 2006;33:539-544.
11. Torma H, Berne B, Vahlquist A. UV irradiation and topical
vitamin A modulate retinol esterification in hairless mouse
epidermis. Acta Derm Venereol 1988;68:291-299.
12. Matsumura Y, Ananthaswamy HN. Toxic effects of ultravio-
let radiation on the skin. Toxicology and Applied Pharmacol-
ogy 2004;195:298-308.
13. Chiller KG, Washington C, Sober AJ, Koh HK. Cancer of the
skin. In: Kasper DL et al., eds. Harrisons Principles of Inter-
nal Medicine. 16thed. New York: McGraw-Hill; 2005:497-
503.
14. Nghiem P, Kupper TS. Basal- and squamous-cell carcino-
mas. In: Jameson JL, Collins FS eds: Principles of Molecu-
lar Medicine Molecular Genetics, Humana Press Inc, New
Jersey; 1998:785-788.
15. Horta MCR, de Assis LAP, de Souza AF, de Araujo VC, Go-
mez RS, Aguiar MCF. p53 and p21 WAF1/CIP1 overexpres-
sion at the invasive front of lower lip squamous cell carci-
noma. J Oral Pathol Med 2007;36:88-92.
16. Leffell DL. The scientific basis of skin cancer. J Am Acad
Dermatol 2000;42:518-522.
17. Gronskov K, Ek J, Brondum-Nielsen K. Oculocutaneous al-
binism. Orphanet J Rare Dis 2007;2:43-53.
18. Bolognia JL, Braverman IM. Skin manifestation of internal
disease. In: Kasper DL et al., eds. Harrisons Principles of In-
ternal Medicine. 16thed. New York: McGraw-Hill; 2005:296-
311.
19. Hong ES, Zeeb H, Repacholi MH. Albinism in Africa as a
public health issue. BMC Public Health 2006;6:212-222.
20. McBride SR, Leppard BJ. Attitudes and beliefs of an al-
bino population toward sun avoidance. Arch Dermatol
2002;138:629-632.
21. The South African Weather Service. Personal Communica-
tion 11 September 2009.
22. Ulrich M, Maltusch A, Rewert-Huber J, Gonzlez S, Sterry
W, Stockfleth E, et al. Actinic keratoses: non-invasive diag-
nosis for field cancerisation. Br J Dermatol 207;156(suppl
3):13-17.
23. Rossi R, Assad GB, Buggiani G, Lotti T. Photodynamic ther-
apy: treatment of choice for actinic cheilitis? Dermatol Ther
2008;21:412-415.
24. Brawley OW, Kramer BS. Prevention and early detection of
cancer. In: Kasper DL et al., eds. Harrisons Principles of In-
ternal Medicine. 16thed. New York: McGraw-Hill; 2005:441-
447.

European Journal of Dentistry

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