Nonepithelial Cells and Hormone Receptors


Mucosa and skin, including that of the vagina, urethra, and vulva have immune surveillance mechanisms termed mucosa-associated lymphoid tissue (MALT) and skin associated lymphoid tissue (SALT) including the vulva. Consequently, occasional single intraepithelial lymphocytes are seen in the epithelium and stroma of all regions of the vulva and urethra. Jones found more in the labium minus than labium majus (11). However, not infrequently, asymptomatic women show a greater number of lamina propria lymphocytes, particularly in the vestibule, where they may be associated with minor vestibular glands and their ducts (Fig. 16). Consequently, the clinical significance of such an infiltrate in symptomatic women is doubtful.

Langerhans' Cells

Langerhans' cells are a specialized type of histiocyte that function as antigen uptake and presenting cells, which are part of the MALT and SALT systems. They migrate from the epithelium to lymph nodes and enter the lymphatic and venous circulations. About 1 intraepithelial Langerhans' cell is found per 10 basal squamous cells. They can be demonstrated immunohistochemically with CD1a (human leukocyte antigen DR receptor) and S100. These markers show the dendritic nature of the cytoplasm.


The pigment-producing melanocytes reside in the basal layer of skin. While scarcely discernible as small, angulated cells with clear cytoplasm on routine-stained sections, they are much better seen when marked with S100, HMB 45, or MART-1. There is about 1 melanocyte per 10 basal cells. The degree of skin pigmentation relates to melanocyte activity, not number, which is the same in all races. The presence of melanocytes usually ends abruptly at the skin-mucosal junction, and they are only rarely found in the vestibular or vaginal mucosa.

Merkel Cells

Merkel cells are postulated to be keratinocyte-derived specialized neuroendocrine cells functioning in the perception of mechanical stimuli. They appear as single and clustered, subbasal, round, and angular cells with clear cytoplasm in the epidermis, hair follicles, and squamous mucosa. Long cytoplasmic processes keep them in contact with keratinocytes and contiguous nerve fibers in the dermis. Their distribution varies dramatically, but they usually number about 1 per 10 basal cells. They are not usually discerned with routine stains, but mark with CK20, synaptophysin, chromogranin, neuron-specific enolase, neurofilament, CK7, CK8, and CK18, and S100.

Hormone Receptors

The vulva and vagina show estrogen and progesterone receptors in the epithelium, stroma, and fat. Estrogen and progesterone receptors are found in squamous mucosa, where they are identified in all basal cells with a gradual decrease toward the maturing surface of the epithelium (Fig. 18) (16). They abruptly cease at the skin-mucosal junction and are not found in keratinized skin with the exception of the mammary-like glands. Stromal estrogen and progesterone receptors are confined to superficial fibroblasts, including the stellate or multinucleated myofibroblasts of the lamina propria and dermis. Unlike the mucosa, the stromal receptors extend into skin beyond the skin-mucosal junction. Fat also shows estrogen and progesterone receptors. The lateral, hair-bearing vulva contains androgen receptors (17).

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