Human papillomavirus associated Bowen's disease of the foot: unique clinical features mimicking a common wart

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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