was 3 years and 5 months (range 3 months to 10 years) [15]. For vulvar EMPD, the mean time to recurrence was shorter after surgery with positive margins (49 months) than negative margins (73 months) [11]. These studies suggest that long-term follow-up is mandatory in patients with EMPD.

22.6.2.1 Mohs Surgery for EMPD

In 1979, Fred Mohs wrote that “the microscopically oriented histographic surgery technique offers the most reliable means of removing all neoplastic disease in EMPD and preserves as much normal tissue as possible” [27]. Since his writing, multiple case series have been published that confirm the efficacy of Mohs surgery for EMPD. Published series using Mohs surgery with hematoxylin and eosin staining demonstrate a recurrence rate ranging from 0% to 28%, with varying duration of fol- low-up [26, 28, 29]. In a survey of Mohs surgeons, Coldiron et al. reported cumulative recurrence rates of 27%, 17%, and 28% after using Mohs surgery to treat EMPD of the female genitalia, male genitalia, and perianal skin, respectively [18]. Hendi et al. reported treating 19 primary tumors with Mohs surgery with a 16% recurrence rate [26]. They also treated 8 recurrent tumors with Mohs surgery and reported a 50% recurrence rate. These series were published prior to the incorporation of CK7 immunostaining into Mohs surgery.

A recent comparison of men and women with genital EMPD treated with Mohs surgery or a variety of

alternatives including wide local excision with margins up to 3 cm, vulvectomy, and hemivulvectomy found a recurrence rate of 18% in the Mohs surgery group versus 36% in the collective group treated with wide local excision, vulvectomy, or hemivulvectomy [4].

The average number of stages for patients with EMPD treated with Mohs surgery is 3 [28, 29]. EMPD also demonstrates one of the largest discrepancies between initial estimate of the clinical extent of tumor and final defect size. A series of ten patients with EMPD treated at one institution found a difference of 75 cm2 between mean lesion size at presentation and mean defect size after completion of Mohs surgery, with a ratio of defect to lesion size of 3.2 [29].

22.6.3Mohs Surgery with CK7 Immunostaining

As previously discussed, CK7 has proven to be a sensitive marker for detecting the presence of neoplastic cells in EMPD, with near 100% positivity in primary and secondary EMPD. Over the past decade, CK7 has been increasingly implemented in Mohs surgery, improving the detection of subtle disease that would otherwise go unseen. Figures 22.2 and 22.3 demonstrate an example where EMPD is unapparent on hematoxylin and eosin stained frozen section (Fig. 22.2) but apparent on CK7 stained frozen section (Fig. 22.3). In cases treated with

Mohs surgery using CK7 in addition to hematoxylin and eosin, hematoxylin and eosin negative but CK7 positive foci are visualized in about 65% of cases (authors’ experience). This suggests that the false negative rate may be as high as 65% when not using Mohs surgery with CK7, a possible explanation for the higher recurrence rate of EMPD compared to basal-cell and squamous-cell carcinomas treated with Mohs surgery. The recurrence rate of EMPD after Mohs surgery with the addition of CK7 has not yet been published, but preliminary data suggest a significant reduction in recurrence rates (authors’ experience).

22.6.4 Peripheral Mohs Surgery

Peripheral Mohs surgery, as seen in Fig. 22.4, has been used for large tissue areas, >8 cm, with superficial/intraepidermal involvement and no histologic or clinical evidence of invasive disease [26]. In this modification, the peripheral margin of the tumor is initially excised using Mohs surgery to remove 2–3-mm-wide strips of epidermis, dermis, and subcutaneous tissue. These peripheral pieces are processed and evaluated using CK7 immunostaining to augment hematoxylin and eosin staining. After clearing the margin peripherally, the remaining central island of tumor, containing skin, adnexa, and superficial subcutaneous tissue, is excised at the level of the mid-sub- cutaneous tissue. This assures removal of the epidermal tumor, along with any tumor that may extend down the adnexa. Histologic evaluation of the entire deep margin of

Fig. 22.4 The peripheral Mohs surgery technique allows for effective and time-saving treatment of histologically confirmed non-invasive EMPD

these superficial lesions is not undertaken. This modification has been performed as an alternative to save time and expense of microscopic examination of extremely large tissue areas. This method is not suitable for EMPD with histologic or clinical evidence of invasive disease [26].

22.6.5 Scouting Biopsies

Scouting biopsies have been proposed as an alternative method to improve the accuracy of the first stage of Mohs surgery, potentially reducing the number of stages needed to clear EMPD, shortening the total duration of the procedure, and reducing operative