Multiple Bowen's disease of the fingers

ARTICLE

In several recent studies, a relationship between genital or digital Bowen's disease (BD) and mucosal types of human papillomaviruses (HPVs) has been reported [1-6] In particular, HPV type 16 has been demonstrated in the majority of cases with BD. The common surgical treatments for BD are excision, curettage, and CO₂ laser therapy. Moreover, useful or beneficial treatments for BD also include liquid nitrogen (LN₂) cryotherapy, topical 5-fluorouracil, injection of bleomycin and photodynamic therapy [7, 8].

In this paper, we report a case of a patient with multiple BD of the fingers, who was treated by excision of lesions, topical application of bleomycin and several courses of LN2 cryotherapy. In addition, the oncogenic virus HPV type 18 was detected in the lesions of this patient.

Case report

An 80-year-old male, who had practiced as a gynecologist for about 40 years, developed multiple small warty lesions and an erythematous plaque on the fingers of his left hand. The lesions slowly developed in size despite topical application of corticosteroid and antibiotic ointments. He had no history of radiation therapy or arsenic ingestion. Clinically, one of the lesions was a sharply demarcated erythematous plaque, 15 x 17 mm in diameter, on the periungual site of the second finger of his left hand. Two small greyish to brownish nodules, 2.0 mm to 2.5 mm in diameter, were found on the third finger of his left hand (Fig 1). We performed a skin biopsy from the lesion on his second finger and excised the two nodules on the third finger of his left hand under local anesthesia. Histologically, all three lesions showed the typical histopathology of BD (Fig 2a). Topical application of bleomycin (5 to 10 mg/day) and three courses of LN₂ cryotherapy (two freeze thaw cycles of 10-15 sec) on the periungual site of the second finger of his left hand, including a 3 mm margin around the skin lesion, was performed and the lesion disappeared gradually. Six months later, we performed a biopsy on the periungual site of his second finger. Histopathologically, it contained no atypical cells with hyperchromatic mitotic nuclei throughout the whole epidermis (Fig. 2b).

Total cellular DNA was extracted from the frozen tissue according to standard procedures [5]. The presence of HPV DNA was examined by polymerase chain reaction (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', reverse 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. Positive PCR products were then digested with four restriction enzymes, DdeI, HaeIII, RsaI, and FokI for 4 h at 37° C and the digested fragments were run on a 4% agarose gel and visualized with ethidium bromide staining. HPV type 18 was determined by restriction fragment length polymorphism analysis compared with the prototype of HPV type 18 DNA.

Discussion

Chronic sun damage, a history of arsenic ingestion, or radiation therapy have all been implicated in the pathogenesis of multiple BD of the fingers [5]. In 1983, since Ikenberg et al. [1] originally reported the correlation of BD and HPV, many studies concerning the relationship between BD and HPV have been published [2, 6]. In particular, BD of the genitalia and fingers are generally associated with HPV infection [1, 6]. HPV type 16 is usually correlated with BD lesions, although other genotypes, which are related to mucosal HPV types, are sometimes detected in BD lesions [2, 10]. HPV types detected are usually limited to a group of mucosal types in BD of the hands. Among HPV genotypes, HPV type 18 is regarded as an oncogenic virus and often is detected in cervical cancer [11]. Oncogenic HPVs encode at least 3 proteins (E5, E6, and E7) that have growth-stimulating and transforming properties. In addition, the expression of oncogenic HPV E6 and E7 proteins enhances the integration of foreign DNA into host-cell DNA, which results in increased mutagenesis [12 ]. In this case, an oncogenic high risk virus, which is usually detected in cervical cancer, was found. Our patient had practiced as a gynecologist for 40 years, and he had rarely examined patients with cervical cancer without wearing gloves. Therefore, he was infected with HPV type 18 through a small injury of his fingers and this had developed into the BD lesions. In general, LN₂ cryotherapy, topical application of 5-fluorouracil, injection of bleomycin, excision, curettage, and CO₂ laser therapy are accepted treatments for BD [7, 8]. Moreover, topical application of bleomycin (5 to 12.5 mg/day) is also used to treat skin cancers and is effective in treating such lesions without severe side effects [13]. However, pre- and post-treatment biopsies are usually considered necessary. After application of bleomycin and several courses of LN2 cryotherapy to treat BD lesions, an improvement was seen, as shown in Figure 2b. One year later, the lesion has not relapsed in any of the fingers of his left hand. However, continued careful observation is required for this patient, because HPVs can exist even in normal skin [14].

Article accepted on 31/1/02

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