ARTICLE
Bowen's disease (BD), which is classified in the category of carcinoma
in situ, usually presents as a single erythematous plaque or nodular
lesion, but sometimes shows a pigmented feature [1, 2]. Recently, BD of
the genitalia and fingers have been shown to be strongly linked to the
mucosal type of human papillomavirus (HPV) infection [3-8], and among
them, HPV type 16 (HPV-16) is typically identified in BD lesions. Here
we report a case of an HPV-associated BD lesion found on the left dorsal
foot of a 56-year-old female patient that mimicked a common wart.
Case report
A 56-year-old Japanese female noticed a small warty lesion on her left
dorsal foot about 7 years before coming to our clinic. It had gradually
developed in size without involving any other parts of her body, including
her hands. Physical examination revealed a well-demarcated, rough surfaced,
round-shaped nodule, 8 x 7 mm in size, on her left dorsal foot (Fig.
1). Clinically, the lesion was diagnosed as a common wart, but a skin
biopsy was taken from the lesion for histological confirmation. The specimen
was divided into two parts: One part was fixed in 10% buffered-formalin
solution and was embedded in paraffin for histopathological examination,
and the other part was frozen immediately in liquid nitrogen and was stored
at - 80° C until DNA could be extracted. The histopathological findings
of the biopsy specimen were compatible with those of BD, not with those
of common warts (Fig. 2). There was no so-called cytopathic effect
[9] often found in common and flat warts, in the granular layer of the
epidermis. Total cellular DNA was extracted from the frozen tissue according
to the standard procedure [10]. The presence of HPV DNA was examined by
PCR using L1C1/C2(C2m) primer sets located in the L1 open reading frame
[9]. The sequences of this primer set are as follows: forward primer;
5'-CGT AAA CGT TTT CCC TAT TTT TT-3', backward primer; 5'-TAC CCT AAA
TAC T(C)CT G(A)TA TTG-3'. The size of the PCR product is approximately
250 base pairs. One hundred ng of total cellular DNA was subjected to
PCR with modification. The PCR products were then digested with four restriction
enzymes, DdeI, HaeIII, RsaI and Fok I for
4 hours at 37° C, separated on 4% agarose gels, and visualized with
ethidium bromide staining under UV irradiation. HPV-16 was determined
by restriction fragment length polymorphism (RFLP) analysis compared with
the prototype of HPV-16 (Fig. 3).
To investigate the histological localization of HPV DNA, in situ
hybridization was performed using 4 µm thick sections on silan-coated
glass slides, as described previously [7]. HPV-16 positive cells with
nuclear staining were observed in the upper layer of the epidermis (Fig.
2).
Discussion
Clinically, BD presents as a well-demarcated and erythematous plaque
or nodular lesion, but sometimes appears as a pigmented plaque or nodular
lesions [1, 2]. BD may develop not only in sun exposed areas of the face
and hands, but also in non-exposed areas including the genital region.
In recent studies, BD of the genitalia and fingers has been strongly linked
to the mucosal type of HPV infection [3-8]. HPV transmission by genital-finger
contact is usually associated with the development of BD lesions, although
there are some reports of HPV-induced BD occurring at other sites [8,
12, 13]. Stone et al. used Southern blot hybridization [12] to
correlate the presence of HPV-16 DNA with the development of BD on the
foot. Clinically, that case did not show verrucous features but presented
as an erosive plaque, while in contrast, our case showed exceptional features
that mimicked a common wart.
Common warts usually appear on the hands and feet. Initially we considered
our case to be a common wart, but we did not find similar lesions at any
other sites, and therefore we biopsied that lesion. Histopathologically,
it had the typical features of BD and no vacuolated cells were found in
the upper epidermis of the lesion. PCR with RFLP analysis showed that
the lesion contained HPV-16 and viral DNA was localized in the nuclei
of tumor cells in the upper layer of the epidermis by in situ hybridization.
These findings show that HPV-16 DNA actually exists in the BD lesion and
that the lesion did not show the so-called cytopathic effect usually found
in common or flat warts. Although the infectious route causing this lesion
is not clear, our case suggests that some instances of BD with an oncogenic
HPV-16 can be clinically quite similar to common warts.
Article accepted on 19/4/01
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