Fig. 22.1 EMPD typically presents with erythematous plaques, sometimes with erosions and ulcerations

anogenital areas. The disease can also present with scale, nodules, verrucous lesions, and hypopigmentation to depigmentation.

22.3.2 Prognosis

Patients with primary EMPD have a significantly better prognosis than those with secondary EMPD because of coexistent malignancy in the latter group. In terms of overall survival, primary EMPD confined to the epidermis has an excellent prognosis. Though evidence is limited and firm conclusions are difficult to make, primary EMPD restricted to the epidermis with no dermal involvement is reported to have no risk of metastasis [4]. Prognosis of invasive EMPD is closely related to depth of invasion from the dermoepidermal junction, with tumors <1 mm carrying zero to minimal risk of nodal involvement. Microscopic invasive disease (<1 mm) is also believed to have no adverse impact on survival. EMPD >1 mm depth has an increased risk of nodal involvement and metastasis. Overall, patients with primary invasive EMPD have a 5-year survival around 72%. In cases with palpable lymph node involvement, however, the prognosis is significantly worse, with 5-year survival reportedly 0% [5].

Though associated adnexal adenocarcinoma is controversial in terms of its pathogenesis and relationship to EMPD, the presence of adnexal adenocarcinoma signifies a worse prognosis. Patients with EMPD and

Summary: Clinical Subtypes

•EMPD most commonly affects vulvar, penoscrotal, perianal, and axillary regions.

•The vulva is the most commonly affected site in women, the penoscrotal/pubic area in men.

•Perianal and penoscrotal EMPD are more commonly associated with coexistent internal malignancies.

•Perianal EMPD is more likely to be associated with lower gastrointestinal malignancy.

•Penoscrotal EMPD is more likely to be associated with genitourinary malignancy.

22.4Clinical Subtypes

22.4.1 Vulvar EMPD

The vulva is the most common site for women to be affected by EMPD. Primary EMPD is far more prevalent, but secondary vulvar EMPD has been described in association with endometrial, endocervical, vaginal, urethral, and bladder neoplasms [5]. The mean age of diagnosis of vulvar EMPD is 69 years of age, with 92% of women presenting postmenopause. Pruritus is the most common presenting symptom, affecting 91% of women. It is often accompanied by a burning sensation. Erythematous-white plaques appear in almost all (98%) patients [11]. Pain is a less common complaint, affecting around 11%. The disease is unilateral in 54% of women. The labia majora are most commonly involved (68%), while the labia minora are involved in 57% of patients. Less frequently, the disease involves

the clitoris (20%), the perianal skin (18%), and the perineum (18%) [11].

Diagnosis of vulvar EMPD is delayed by an average of 20 months, with most patients treated for fungal infection or postmenopausal vulvovaginitis prior to diagnosis of EMPD. Delayed diagnosis leads to a statistically significant increase in lesion size but not tumor depth. In a series of 56 patients, invasive disease was reported in 18% [11]. Interestingly, in this series, recurrence rate was not related to size of the tumor or positive margins on excision. The only factor found to be predictive of recurrence was perineal involvement. Women with involvement of the perineum experienced recurrence both more often and in a shorter time frame compared to those without.

22.4.2 Perianal EMPD

Perianal EMPD (PPD) is less common than other subtypes, representing about 20% of cases of EMPD [12]. Its presence, however, is correlated more often than other subtypes with underlying malignancy, especially cancer of the anus or colorectum. Reports suggest a rate ranging from 33% to 86%, with the interesting exception of Chinese male patients who have a rate of underlying malignancy reported to be as low as 4.5% [12].The largest literature review to date revealed that in 58% of cases of PPD, the disease was cutaneous only, while in 10% of cases there was an associated synchronous or metachronous internal neoplasm, 28% of cases were reported to demonstrate intraepidermal spread of rectal carcinoma, and 1% of cases were associated with a cutaneous adnexal carcinoma [13]. The authors conclude that PPD exists in several clinical scenarios: primary EMPD, EMPD associated with adenocarcinoma of adnexal structures (either retrograde skin invasion by an adnexal carcinoma or an adenocarcinoma involving the epidermis and adnexal structures), and anorectal carcinoma with pagetoid spread [13]. The last scenario may include cases of adenocarcinoma mislabeled as EMPD.

Most patients with PPD who have underlying internal malignancy present with synchronous visceral malignancy and cutaneous disease. Internal malignancies reported in association include colon adenocarcinoma, prostate cancer, esophageal cancer, and lung cancer, though many of these may represent spurious reports of unclear significance. Perianal EMPD should

prompt careful evaluation for a coexistent tumor, however, especially of the lower gastrointestinal tract.

22.4.3 Penoscrotal EMPD

Penoscrotal EMPD is often misdiagnosed, with reports documenting a rate up to 90% [14]. The most common diagnoses made prior to the correct identification of EMPD are chronic eczema and tinea cruris [14]. The average age at diagnosis is 64 years old. Average time from onset of symptoms to accurate diagnosis is about 4 years [15]. In a large case series of patients, lesion size at presentation ranged from 3 to 250 cm2. Disease was limited to the scrotum in 59.2% of patients, whereas in 36.2% of patients, EMPD involved the scrotum, penis, and/or suprapubic skin [14].

Penoscrotal EMPD, like perianal EMPD, is more commonly associated with an underlying neoplasm in locally adjacent organs and structures, including cancer of the prostate, urethra, bladder, and testicles. Presence of EMPD on the penis or scrotum should lead to a thorough investigation for underlying internal malignancy.

22.4.4 Triple EMPD

EMPD involving the genital region as well as the bilateral axillae has been reported, primarily in Japanese men [16]. In all reported cases, the genital lesions preceded axillary involvement. Any patient with genital EMPD should undergo a thorough examination to exclude additional cutaneous involvement.

22.4.5 Unifocal or Multifocal Disease?

With multiple cases of triple EMPD reported and the well-documented tendency of EMPD to have significant subclinical extension with recurrence despite apparently clear margins, much has been written and speculated about the possible multifocal nature of at least some cases of EMPD. Uncertainty exists as to whether the tumor grows in a contiguous pattern or is the result of a field of cancerization with multiple foci [17]. Multifocal disease has been defined as the absence of tumor cells at the surgical margins of two clinically distinct, excised lesions. Many reports exist