with grafts from the inner arms which provide a good match in color and texture and allow for inconspicuous closure of the donor site. Skin from the lateral external portion of the lower limb could also be used to reconstruct defects on the genitalia resulting in satisfactory color and texture match in the recipient site. Significant urethral involvement may be managed utilizing mucosal grafts from the buccal epithelium.

Summary: Common Genital Lesions Treated with Mohs Micrographic Surgery

•Basal cell carcinoma

•Squamous cell carcinoma in situ, including erythroplasia of Queyrat, Bowen’s disease (intraepithelial carcinoma), and cutaneous horn

•Invasive squamous cell carcinoma

•Malignant melanoma in situ

•Malignant melanoma

•Extramammary Paget’s disease

•Dermatofibrosarcoma protuberans

•Granular cell tumor

•Kaposi’s sarcoma

•Leukemias (including lesions of cutaneous T cell lymphoma) and lymphoblastomas

•Langerhans cell histiocytosis

•Hemolymphangioma

•Localized metastases

Fig. 29.2 SCC on the shaft of the penis

perianal regions. Scrotal BCCs often present as persistent ulcerations or plaques without identifiable predisposing factors. These lesions are often poorly circumscribed with relatively high recurrence rates when treated with standard excisions. Furthermore, metastatic disease may be more common as compared to BCCs arising from non-genital locations. Therefore, MMS, which offers the highest cure rate while sparing tumor-free surrounding tissue, is considered the gold standard of treatment for BCCs in the genital region and is the most appropriate initial therapeutic approach.

Although basal cell carcinoma (BCC) is the most common human malignancy, BCCs arising on non-sun- exposed genitalia are rather uncommon and have an unclear pathogenesis [1]. A delay in diagnosis can result in larger and more invasive tumors and increased potential for scarring, anatomic deformity, functional compromise, and tumor recurrence. There have been several reports in the literature of BCCs arising in the vulvar region, with some tumors presenting with characteristic BCC-like lesions and others presenting with nonspecific symptoms such as unilateral pruritus [2]. BCCs have also been reported on the scrotum, perineum, and

By far, the most common form of penile and vulvar carcinoma is SCC (Fig. 29.2 and 29.3). The incidence of penile carcinoma is significantly higher in some emerging countries as compared to developed nations. This is thought to be due to socioeconomic disparities and religious behaviors that contribute to the different incidence rates, as poor local hygiene has been recognized as unfavorable risk factor, while circumcision shortly after birth has been recognized as favorable risk factor. Ritual practice of circumcision seems to influence the prevention of penile cancer statistically, as early circumcision seems to be associated with a lower

Fig. 29.3 Invasive squamous cell carcinoma of the penis measuring 6.0 x 5.0 x 5.0 cm (a) involving the prepuce, glans penis, and urethral meatus, cleared after 5 stages of MMS (b), and repaired with a combination of advancement of the penile

shaft to repair the prepuce and ventral surface of the distal penis, as well as a full-thickness skin graft from the inner arm for reconstruction of the dorsolateral glans penis (c)

incidence of penile cancer compared to later circumcision. Most often, penile SCCs develop in patients over the age of 50. The common presentation for penile cancer is balanoposthitis, followed by an ulcerated lesion, and the most common site where penile cancer occurs is on the glans, followed by the prepuce [3].

Squamous cell carcinomas (SCCs) in the non- sun-exposed genital region have been reported to occur most commonly in the setting of human papilloma virus infection and preexisting chronic inflammatory conditions, such as lichen sclerosus et atrophicus and lichen planus. Balanitis xerotica obliterans (penile lichen sclerosus et atrophicus) may precede, coexist with, or develop after the development of SCC. Non-verruciform low-grade squamous carcinomas, which are strongly

associated with lichen sclerosus, are more frequent in the foreskin of elderly men. These lesions are often multicentric, and subsequent independent tumors may show some verrucous features. Likewise, balanitis has a chance of progressing to squamous cell carcinoma, and if not adequately treated, may lead to invasion.

Premalignant lesions associated with SCC include cutaneous horn, pseudoepithelioma, keratotic and micaceous balanitis, balanitis xerotica obliterans, giant condyloma, and bowenoid papulosis. SCC in situ of the penis includes erythroplasia of Queyrat and Bowen’s disease, which can progress to invasive SCC, with the potential for metastasis to local lymph nodes and distant sites. Risk factors include poor hygiene, being uncircumcised, smoking, and phimosis.

Additionally, HPV coinfection is present in a significant percentage of patients with penile carcinoma. Clinically, invasive SCCs may be either papillary or cauliflower-like, or sclerosing and infiltrating. The prognosis is somewhat better for the former variant.

Penile carcinoma is an aggressive disease with significant treatment-associated urologic and psychosexual morbidity, particularly when partial or complete penectomies are performed instead of tissue-sparing techniques such as MMS. For this reason, MMS is optimal in order to minimize interference with functional anatomy without compromising local cancer control. As a surgical treatment that allows for the highest possible cure rate, maximum tissue sparing, and complete margin control, MMS is considered the treatment of choice for in situ and invasive SCCs of the penis. Due to its ability to metastasize to the lymph nodes, MMS may help minimize the risk of recurrence and ensuing metastasis, with multiple reports in the literature substantiating the successful use of MMS for invasive SCCs of the penis.

Penile SCCs affecting the urethral meatus have a significant propensity for tracking along the urethral epithelium (Fig. 29.3), and the extent of this involvement may be difficult to estimate clinically. MMS is the optimal treatment in this case, as only involved urethral mucosa is removed, without risking missing subclinical urethral spread.

Microscopically, carcinoma of the scrotum (chimney sweeps’ disease) is most often Bowen’s intraepithelial carcinoma or invasive squamous cell carcinoma. Originally, soot and tar products were suspected as factors. Today, this occupational disease is seen also in persons working with mineral oil, paraffin, and tar. Early recognition of chronic warty or eczematousappearing growths on the scrotum is critical.

Vulvar SCCs arising on the labia minora, majora, and at the vaginal vestibule, as with the lesions mentioned above, are all also best treated by MMS.

Intraepithelial carcinoma (Bowen’s disease) of the anus is diagnosed with increasing frequency, as is in situ carcinoma of the vulva, which is also now diagnosed in younger patients than in the past. The reason for this apparent increase in frequency is unknown. Infection by herpes simplex virus type 2 and human papilloma virus are prime suspects in carcinomas arising in the anus and the female lower genital tract. The extensive involvement of the anal mucosa by Bowen’s

disease and its potential to become invasive carcinoma necessitate a surgical approach that is concerned with both cure as well as preservation of anal function. Of note, squamous cell carcinoma in situ of the vulva frequently involves the perianal skin and anal mucosa. Furthermore, the anogenital region, comprising the cervix, vagina, vulva, perineum, and anus, has the potential for the development of multicentric and multiple primary malignancies. All of these tumors are best treated with MMS, which allows complete control of the margin and gives the best results in terms of the cure and sparing tissue in these regions, often with good cosmetic and functional results.

29.4.3In Situ and Invasive Malignant Melanomas

Although uncommon, melanoma of the male and female genitalia is not very rare. The potentially higher incidence of malignant melanoma arising in the nevi on the genitalia has led some to advocate that pigmented nevi of the genitalia be excised when discovered. Metastasis occurs rapidly from malignant melanoma of the anogenital region, possibly due to delayed diagnosis as compared to cutaneous melanomas.

The results of multiple investigators have confirmed the value of MMS in the treatment of malignant melanoma. The success of MMS confirms that melanoma grows in a contiguous fashion before it spreads systemically. It is known that once tumor metastasizes from the primary site, trying to improve survival by increasing the extent of conventional surgery is typically fruitless. Therefore, the goal of surgery is to remove the entirety of the primary tumor, including any subclinical extensions. The value of MMS is the ability to identify these extensions microscopically and to excise tumor-bearing tissue while sparing normal skin. Furthermore, MMS may spare a significant diameter of normal skin that may be removed with fixed-margin standard surgical excisions for melanoma, a distinct advantage to patients whose melanomas are on the genitalia and in patients whose melanomas have indistinct clinical margins and who would require an even wider margin of normal skin when using standard surgical techniques and who are at substantial risk of tumor recurrence and subsequent metastasis.

In recent years, techniques have been developed to enhance the ability to detect melanoma cells on frozen section slides. During MMS for melanoma, tyrosine and silver stains, in addition to more commonly used Melan-A and MART-1 immunohistochemical stains, can be used to highlight premelanin, melanin, and melanocytes. The use of these stains during MMS allows for improved clearance of malignant melanoma while preserving as much of the healthy surrounding tissue as possible by improving the sensitivity and specificity of the microscopic examination of the excised margins.

29.4.4 Extramammary Paget’s Disease

Extramammary Paget’s disease (EMPD) is an uncommon intraepithelial neoplasm typically occurring in apocrine-gland-rich regions. EMPD usually involves the epidermis but may extend into the dermis, and deeper invasion can occur. The anogenital region is a very common site of occurrence, with the most commonly involved anatomical sites being the vulvar, perianal, perineal, scrotal, and penile regions. Its peak incidence is in patients between 65 and 70 years of age, and postmenopausal Caucasian women are most commonly affected. However, in some populations, such as the Asian population, EMPD seems to affect more men than women, and the scrotum and perianal areas are the most commonly involved sites. The onset of EMPD is insidious. Clinically, the lesions typically present as well-defined, moist, and erythematous plaques usually accompanied by pruritus or other nonspecific symptoms such as bleeding, edema, burning, or pain. EMPD tends to carry a good prognosis because the spread of atypical cells is usually limited to the epidermis.

Histopathological examination shows epidermal acanthosis and elongated rete ridges. Paget’s cells are large, mucin-containing intraepidermal cells with a large nucleus and abundant pale cytoplasm (Fig. 29.4). Recent studies of perianal and vulvar EMPD have described distinct immunohistochemical subtypes termed cutaneous and endodermal. Cutaneous EMPD is characteristically positive for cytokeratin 7, negative for cytokeratin 20, and positive for gross cystic disease fluid protein 15, whereas endodermal EMPD is positive for cytokeratins 7 and 20, while it stains negative for gross cystic disease fluid protein 15. Consequently, intraoperative cytokeratin-7 immunostaining may be

used with MMS for EMPD. In addition, to facilitate identification of involved tissue, a rapid carcinoembryonic antigen stain has also been reported to have been used as an adjunct to conventional H&E-stained slides to enhance the ability to obtain clear margins with MMS [4]. This technique was particularly useful in highlighting involvement in areas of marked dysplasia and artifact where discrimination is often difficult. Specifically, in anal epithelium, the presence of goblet cells may complicate discrimination of EMPD from normal epithelium.

Since it is a malignant lesion, surgery remains the treatment of choice. Wide surgical excision is currently the standard treatment for EMPD. However, EMPD almost always extends well beyond its clinically apparent borders. Consequently, standard excision is often insufficient to achieve complete remission, with EMPD having a notoriously high rate of recurrence after wide local excision. Recurrence is often associated with invasion. Therefore, MMS should be considered the gold standard of treatment for nonmetastatic EMPD.

Effective clearance of EMPD with Mohs micrographic surgery was first reported in 1979 [5]. It has since been suggested that this malignancy may be multifocal, particularly as reports of recurrences after resection with MMS have appeared. However, investigators have found the tumor to be unifocal with thin, long, and finger-like projections extending from the main body of tumor [6]. As such, if there are any doubts, an additional resection of a margin of tissue may be considered even after clear surgical slides are obtained. Overall, MMS has been shown to achieve a significantly lower recurrence rate for EMPD as compared to standard wide excision [7].

The alternative to MMS is wide local excision with a 4-cm surgical margin. In comparison, MMS is a tissuesparing technique that not only minimizes the size of the surgical defect in comparison to wide local excision but also provides the best cure rates. Furthermore, multiple scouting biopsies, which can be processed as either permanent or frozen sections prior to initiating MMS, can be a beneficial adjuvant technique and can be used to guide the extent of the initial Mohs layer, allowing for MMS to more rapidly clear tumors with the best preservation of the healthy surrounding tissue [8]. In addition, there have been reports of 5-fluorouracil being applied topically for 10 days prior to MMS, resulting in a sharply delineated, erythematous patch of biopsy-proven EMPD well beyond the original clinical borders [9].