Case reports: Bowen's disease of the penis treated with topical imiquimod 5% cream

Journal of Drugs in Dermatology, May, 2008 by Sumayah J. Taliaferro, George F. Cohen

Abstract

Bowen's disease of the penis is relatively uncommon, but the prevalence has increased in recent years. Risk factors for penile squamous cell cancer include smoking, infection with human papilloma virus (HPV), immunosuppression, and a history of conditions such as balanitis, phimosis, and lichen sclerosis et atrophicus. Bowen's disease of the penis is often managed by local excision of the lesion. Less invasive methods are now employed more frequently and include laser ablation, electrodessication and curettage, cryosurgery, application of 5 -fluorouracil, and topical imiquimod 5% cream. This case report describes the successful treatment of Bowen's disease of the penis with topical imiquimod 5% cream in a 42 -year-old African American male with human immunodeficiency virus (HIV) disease.

Introduction

The incidence of penile carcinomas has increased in recent years. The majority of malignant neoplasms of the penis are squamous cell carcinomas (SCCs). Three types of penile SCCs in situ are recognized: Bowen's disease, erythroplasia of Queyrat, and bowenoid papulosis. Bowen's disease and its clinical variant, erythroplasia of Queyrat, may present as a shiny or scaly erythematous patch on the glans penis. Bowenoid papulosis frequently occurs on the penis as discrete, red-brown dome-shaped papules, typically affecting a younger age group. A histological distinction among the 3 types is difficult, and all are generally categorized as intraepithelial neoplasia or SCCs in situ.

Treatment modalities for Bowen's disease of the penis include local and wide excision and destructive techniques. The trend in current therapies aims to avoid aggressive surgical excision to prevent cosmetic deformity and preserve organ function. A case of Bowen's disease of the penis treated with topical imiquimod 5% (AldanC[R]) is described.

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Case Report

A 42-year-old African American male with human immunodeficiency virus (HIV) disease and a history of Kaposi's sarcoma presented with a nonhealing lesion on the penis which had been present for approximately 1 year. Over a 3-month period, he noticed that the lesion began to expand in size, and did not resolve with the application of bacitracin ointment. The patient denied a history of trauma to the area and had a past medical history of cigarette smoking, hyperlipidemia, hepatitis B, and chronic periodontitis. At the time of presentation, the patient's CD4 count was 374 and HIV RNA1 was >75. He was on the following medications: efavirenz, emtric-itabme/tenofovir, fluvastatin, and valacyclovir.

On physical exam, the patient had a well-demarcated pink scaly plaque 1.8X2 cm on the dorsolateral aspect of the shaft of the penis (Figure 1). He had no notable penile discharge, inguinal adenopathy, or testicular masses. No other lesions were noted in the pubic area. Histological examination of a punch biopsy of the lesion revealed SCC in situ (Figure 2). Special stains for periodic acid schiff (PAS) and acid fast bacilli (AFB) indicated negative cultures. The patient was treated with imiquimod 5% cream 3 times per week for 12 weeks while applying petrolatum to the surrounding skin areas to minimize irritation. The plaque cleared and histological resolution was confirmed (Figure 3).

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Discussion

Squamous cell carcinoma of the penis accounts for less than 1% of all cancers in the US. Its prevalence is increasing with the rising rates of HIV disease. Risk factors for penile SCC include immunosuppression, smoking, infection with HPV, and unprotected exposure to ultraviolet light due to phototherapy. Men who have not been circumcised are also at an increased risk. The incidence of SCC of the penis is reportedly rare in countries that routinely practice male circumcision. The occurrence of balanitis, phimosis, and chronic penile dermatoses, such as lichen sclerosis et atrophicus, are proposed risk factors as well.

Although the progression to metastatic disease is uncommon in SCC of the penis, a small percentage of patients may develop an invasive malignancy requiring penile amputation. While the standard ofcare for invasive penile carcinoma continues to be partial penectomy, conservative treatment options are favored for SCC in situ of the penis. Local excision with 5 mm margins has been widely used, but still carries the risk of scarring, deformity, and potential impaired organ function. More recently, laser ablation and Mohs micrographic surgery have been promoted to maximize organ preservation. A few case reports demonstrate successful management of this epithelial neoplasm using neodymiurmyttrium-aluminum-garnet (NdtYAG) laser surgery.2 Other reported treatments include the use of the carbon dioxide laser, photodynamic therapy, topical application of 5-fluorouracil, electrodessica-tion and curettage, and cryosurgery. Several case reports have tecently demonstrated the successful treatment of SCC with topical imiquimod.(3-5)

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Imiquimod 5% cream is a topical imidazoquinoline immune response modulator approved by the FDA for the treatment of genital and perianal warts, actinic keratosis, and superficial basal cell carcinomas. While the precise mechanism of action of topical imiquimod is unknown, it has been shown to activate the innate immune system to produce cytotoxic inflammatory and antiviral cytokines such as interferon-alpha, interleukin-12, and tumor necrosis factor-alpha.6 Imiquimod can stimulate the elaboration of these cytokines via its action on toll-like receptors, which are cell-surface receptors that recognize ligands associated with pathogenic organisms. Imiquimod binds to toll-like receptor 7 and in high concentrations binds to toll-like receptor 8. Both tolllike receptors 7 and 8 are involved in the mammalian immune defense against viral pathogens.'