invasive spread into deeper structures, or adnexal with upward, Pagetoid spread into the epidermis. Nevertheless, vulvar EMPD is reportedly associated with cutaneous adnexal adenocarcinoma 4–8% of the time and an internal malignancy documented 20% of the time [7]. Perianal EMPD is reported to be associated with cutaneous adnexal adenocarcinoma 7% of the time, with internal malignancy documented 14% of the time [7]. These numbers should be interpreted with caution, however, given the difficulty in assessing whether an underlying adnexal adenocarcinoma is truly a separate process.

The phenomenon of potential tumor spread from epithelial lining of internal organs locally contiguous to the skin has also been described, especially in vulvar EMPD. EMPD in association with endometrial, endocervical, vaginal, Bartholin’s gland, urethral, and bladder neoplasms may arise by this mechanism [5].

22.2.4Affected Areas: Sites with Apocrine Glands

Summary: Clinical Presentation and Natural

History

•EMPD is often diagnosed 2–4 years after onset of symptoms.

•Erythematous plaques with pruritus are the most common clinical presentation.

•Primary EMPD has an excellent overall survival but high local recurrence rate.

•The prognosis of invasive EMPD is related to depth of dermal invasion from the dermoepidermal junction.

•The prognosis of patients with secondary EMPD is poor and related to underlying malignancy.

•Though distinguishing EMPD arising in the epidermis with subsequent adnexal adenocarcinoma and EMPD secondary to adnexal carcinoma may be impossible, the presence of deeper adnexal adenocarcinoma signifies a worse prognosis.

EMPD is primarily a disease of apocrine gland-bearing skin. Apocrine glands are thought to function as a scent gland, primarily a form of sweat gland with secretions rich in sialomucin. At birth, apocrine glands are located in abundance in the axillary and anogenital areas. The glands become active in these regions during puberty. Modified apocrine glands are found in the eyelids (Moll’s glands), external auditory canal, and nipple, where the glands contribute lipid secretions to tears, cerumen (ear wax), and milk, respectively. Apocrine glands are also found in the periumbilical region.

Given the abundance of apocrine glands in the vulvar area, it is not surprising that this is the most common site for EMPD in women, with about 67% of all cases presenting in female genital skin [3]. In men, EMPD most frequently affects genital skin. Rare cases have been reported in other apocrine gland-bearing areas, including the eyelids, auditory canal, and periumbilical skin.

Ectopic EMPD, disease occurring in skin without apocrine glands, has been reported on the sternum, buttock, back, chest, scalp, hypochondrium, upper abdomen, and face. The germinative milk line is a possible source for the origination of ectopic EMPD. It has been reported primarily in the Asian population [8, 9].

22.3Clinical Presentation and Natural History

22.3.1 Clinical Presentation

The diagnosis of EMPD is usually made after multiple other diagnoses have been considered and their typical treatment regimens failed. The differential diagnosis includes Bowen’s disease, tinea cruris, contact dermatitis, lichen simplex chronicus, lichen planus, cutaneous T-cell lymphoma, psoriasis, and seborrheic dermatitis [10]. The average time from the onset of symptoms to diagnosis of EMPD is 2–4 years, but protracted courses of over 10 years prior to the final diagnosis are not uncommon. Onset is often insidious, and a high degree of clinical suspicion should be present in any vulvar, perianal, genital, or axillary dermatosis that does not respond to typical therapies.

EMPD presents with a variety of clinical manifestations. Erythematous plaques and pruritus are the most common clinical findings. Figure 22.1 shows an example of the typical clinical presentation. Patients may later develop erosions and ulcerative lesions, with a burning sensation as well as frank pain associated with more advanced lesions, especially in