ARTICLE
Human papillomaviruses (HPV) are small
DNA tumor viruses affecting epidermal (cutaneous) and epithelial (mucosal)
tissues. They are associated with a large variety of different clinical
lesions, ranging from benign common (cutaneous) warts to malignant tumors
of the anogenital area. The number of HPV types analyzed is steadily increasing.
Among these, HPV 29 is identified only on rare occasions.
Case report
A healthy, human immunodeficiency virus (HIV)-negative, 40-year-old
white man presented with a 4-year history of hyper macules on the cheeks
and forehead (Fig. 1).
Local treatment with aceleic acid and retinoid cream brought no improvement.
Skin-biopsies taken from these lesions revealed slight acanthosis of the
epidermis with vacuolization within the keratinocytes in the upper malpighian
layer similar to HPV-induced cytopathic viral effects (Fig.
2). The basal cell layer showed moderate hyperpigmentation. DNA was
extracted from the paraffin embedded material and polymerase chain reaction
(PCR) was performed with the "general'' primer pair RK91, which is able
to amplify viral DNA of approx. 230 bp length of the following HPV types:
1-4,10,11,15,16,26, 27,29,30,53,56,57,65. Sense primer sequence: 5'ACHCCTAGTGGBTCTWTRGTDWC3';
antisense primer sequence: 5'HHTCAWAYTCCTCYAYATGYCT3' (B = C or G or T,
H = A or C or T, W = A or T, Y = C or T). PCR was performed in a total
volume of 50 mul with 2.5 U of the Taq-polymerase AmpliTaq Gold (Perkin
Elmer, Roche Diagnostics, Basel, Switzerland) according to the manufacturer's
recommendations (35 cycles: 1 min 94° C, 1 min 52° C, 1 min
72° C) using the DNA Thermal Cycler 960 (Perkin Elmer, Roche Diagnostics,
Basel, Switzerland). The purified PCR product was then sequenced by dye
terminator cycle sequencing according to the manufacturer's recommendations
(Perkin Elmer Applied Biosystems, Warrington). The sequence comparison
with DNA from HPV types 1-70 demonstrated a > 96.3% homology with HPV
29 DNA. In contrast a comparison with other cutaneous HPV-types revealed
a 43% homology for HPV3 and a 50% homology for HPV10.
Discussion
Spotted hyperpigmentation on sun-exposed sites such as the face can
be quite common. In young people simple freckles must be distinguished
from solar lentigines. The later have a more intensive color and do not
darken or increase in number on sun exposure as freckles do. Simple freckles
show no morphological abnormality on biopsy. Solar lentigines are histologically
characterized by a linear increase in the number of melanocytes at the
dermoepidermal junction without any cytological atypia and no budding
down of these melanocytes into the underlying dermis. Pigmented actinic
keratoses and the flat type of seborrhoeic warts show characteristic changes
within the epidermis.
In 1988 and in 1999, we reported two cases of pigmented bowenoid papulosis
of the neck containing HPV 16 in the first and HPV 18 in the second patient
[1, 2]. Clinically, the lesions on the face of the patient we describe
in this report resembled those found in our patients with extragenital
bowenoid papulosis. However, the microscopic examination of the facial
skin lesions did not show bowenoid features within the epidermis. Nevertheless,
on the basis of finding intracellular vacuolization within the cells of
the upper epidermal layers, we suspected that the lesions could have been
induced by viral infection [3-5]. Using PCR and DNA sequencing we clearly
identified HPV 29 DNA.
HPV 29 was first described by Favre et al.
in 1989, and appears to be related to HPV types associated with common
as well as with flat warts [6]. Later on, HPV 29 was also found in benign
proliferations and in carcinomas of the skin in immunosuppressed patients
[7].
Altogether, the occurrence of HPV 29 is only rarely mentioned within
the extensive HPV-literature. We find it very interesting to detect this
virus type in the unusual lesions of our male immunocompetent patient.
To our knowledge, this is the first case of HPV 29-induced spotted hyperpigmentation
of the face. Our findings suggest that HPV could cause more varied skin
lesions than is generally assumed.
Article accepted on 15/10/01
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