morbidity for patients [30]. Other benefits include a more accurate estimate of the size and type of reconstruction, allowing for a more informed preoperative consultation.

The technique consists of performing multiple punch biopsies, shave biopsies, or scissor biopsies between 1 and 5 cm from the clinically apparent margin, prior to initiating Mohs surgery. Specimens are examined microscopically. CK7 staining may be performed, improving the sensitivity of scouting biopsies. Photographs are used to carefully map the involved margins. This approach has been proposed to be especially useful in situations where the degree of involvement may have a significant impact on disease management. For example, urethral involvement is found suggesting that collaboration with a urologist might benefit the patient, or substantial tumor size leads to the consideration of general anesthesia [30].

Interestingly, false negative results have been reported using the scouting biopsy approach; hence the utility of this method remains to be determined.

Summary: Alternative Treatment Options

•Topical treatment of EMPD with imiquimod and 5-fluorouracil has shown variable success.

•Caution is advised when using topical treatment that may lead to the appearance of clinical cure but persistent subclinical, microscopic disease.

•Topical treatments may also fragment tumor, rendering Mohs surgery less effective.

•Radiation therapy may have a role in select cases of non-invasive EMPD.

•There is no consistently effective chemotherapeutic regimen for metastatic disease.

off-label for the treatment of in situ EMPD, with reports of successful treatment of primary and recurrent tumor both clinically and histologically. Authors propose the use of 5% imiquimod cream at least three times weekly for 8–16 weeks, but case reports exist that demonstrate multiple treatment regimens with varying efficacy [31]. Application of 5% imiquimod cream can be accompanied by a localized inflammatory response that can limit the frequency of application, and some studies have found that higher frequency of application leads to higher cure rates.

Imiquimod cream has also been used in the preMohs surgery setting as a method of reducing the tumor burden prior to excision. Caution should be exercised when using a topical treatment that may partially treat a clinically indistinct tumor, leading to discontinuous growth. Using this approach may unintentionally render Mohs surgery less efficacious at achieving clear margins due to fragmentation of the tumor.

Because of the short duration of follow-up of most reported cases treated with 5% imiquimod, no definitive conclusion can be reached regarding the long-term efficacy and recurrence rate. Once long-term recurrence rates after treatment with imiquimod are better characterized, the topical treatment may prove to be a viable alternative to surgery in select patients. Presently, its use may best be reserved for patients who refuse or are unable to tolerate surgical treatment.

5-Fluorouracil has also been explored as a potential surgery-sparing treatment in EMPD. While reports suggest clinical clearance of tumor after 5-fluorouracil treatment, histologic persistence has been noted. Thus caution should be used when considering treatment with a topical therapy that may lead to masking of persistent tumor including deeper, potentially invasive disease [32].

22.7.2 Photodynamic Therapy

22.7Alternative Treatment Options

22.7.1Topical Therapies: Imiquimod and 5-Fluorouracil

Imiquimod has received considerable attention as a topical immunomodulator, FDA approved for the treatment of actinic keratoses and select non-facial superficial basal-cell carcinomas. Imiquimod has been used

Photodynamic therapy (PDT) with topical ALA or intravenous porfimer sodium followed by treatment with a 632.8-nm argon-pumped dye laser has been used for non-invasive EMPD. Results of a recent retrospective series found 78% (7/9) of patients treated with intravenous porfimer photosensitization and argon laser disease free at follow-up (12–96 months) [33]. Eight of 16 patients treated with PDT using topical ALA had a complete clinical response, and 38% were