Squamous Cell Carcinoma in Situ (Bowen’s Disease)

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Overview

The eponym Bowen's disease is used to describe squamous sell carcinoma in situ on any cutaneous surface except glans penis. Untreated, Bowen's disease may progress to invasive squamous cell carcinoma. Bowen's disease may occur on sun-exposed sites, on extragenital sites where actinic lesions are rare (palms, trunks of persons with no history of sun exposure), in the genital region, and on the glans penis (erythroplasia of Queyrat or penile intraepithelial neoplasia [PIN]). Actinically induced lesions are considered a step in the progression of actinic keratoses to squamous cell carcinoma. Bowen's disease of atypical and sun-protected sites may be associated with exposure to arsenic. When sun-protected Bowen's disease develops into SCC, it may be more aggressive than actinically induced Bowen's disease. When Bowen's disease occurs in the genital area it is often associated with infection with oncogenic human papilloma virus (HPV) strains (most frequently HPV 16 and18), as is PIN. This form of SCC in situ is similar to bowenoid papulosis, however these tend to be solitary lesions that have persisted for many years, now behaving like a lesion of Bowen's disease rather than like HPV infection (bowenoid papulosis). These genital SCCs are more aggressive than actinically induced squamous cell carcinomas. Multifocal Bowen's disease, especially of the lower extremities, is a significant problem in organ transplant recipients (OTR) and other persons with compromised immune systems. They must be managed with care, as progression to carcinoma and aggressive behavior of the ensuing SCCs is the rule.

First Steps

1. Complete surgical excision is effective and is suggested in all patients in whom adequate follow up cannot be assured.
2. Imiquimod applied once daily for 16 weeks may be attempted. The area will become erythematous and may erode. About 20% of patients may not react to imiquimod treatment.

Subsequent Steps

1. If the reaction to imiquimod therapy is painful or erosive, the treatment can be stopped for 1 week and restarted at 3-5 times per week. The full course of treatment is then completed. An alternative approach on the lower legs is to treat in 4-week cycles, with a 4-week holiday between treatment cycles. Two to four such cycles may be required.
2. If there is minimal reaction to daily treatment with imiquimod, the treated site may be occluded to enhance the reaction.
3. The combination of imiquimod 3 times weekly plus 5 fluorouracil cream 5% (5FU) may be used for extragenital and actinic lesions. Imiquimod is applied once at night on 3 alternate days. 5FU is applied at night on the days imiquimod is not used, and every morning. Expect a significant reaction. Cycles of 1 month of treatment followed by a 1-month holiday may be required.
4. For bowenoid papulosis (genital Bowen's disease due to oncogenic HPV), and erythroplasia of Queyrat, topical 5FU twice daily may be used. The lesions are treated for 10 weeks, then reevaluated. Treatment is continued until lesions are completely eradicated.
5. The treated lesion is evaluated 6 weeks after treatment has been completed and followed at regular intervals. Areas of recurrence are biopsied and treated with surgical excision or radiation therapy (for PIN).

Alternative Steps

1. For frail patients or when lesions are not easily excised or treated with topical modalities, or if PIN has failed topical treatment, radiation therapy may be used. It should generally be restricted to patients over 65 years of age.
2. Cryotherapy and 5FU therapy alone are no longer recommended due to the high cure rates obtained with newer topical treatment regimens.

Pitfalls

1. Although a small biopsy from a large lesion may reveal Bowen's disease, invasive
   squamous cell carcinoma may be present in another part of the lesion. Therapies not involving pathologic review may miss this and lead to inadequate treatment.
2. Bowen's disease may occur in non-sun-exposed areas and can be confused for inflammatory skin conditions such as psoriasis. Fixed plaques that do not respond to topical treatment should be biopsied.
3. Bowenoid papulosis of the genitalia is caused by infection with oncogenic HPV types. Histologic features may be identical to those of Bowen's disease. Treatment is with cryotherapy, or 5FU once or twice daily, or imiquimod as described for genital HPV infection.

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