Ridley's The Vulva

The epithelium on the inner aspects of the labia minora is still keratinised, but medially it merges with the vestibule, and this transition is seen clinically as Hart’s line.

The frenulum and prepuce of the clitoris are covered with keratinised stratified squamous epithelium which originates from the labia minora, and sebaceous and mucus‐secreting glands are present. The glans is covered by a thin keratinised epithelium but contains no adnexal or glandular structures.

The vulval vestibule is a mucosal surface and as such is covered by non‐keratinised stratified squamous epithelium rich in glycogen. It is devoid of pilosebaceous units and other adnexal structures.

Bartholin’s glands are lobulated and contain multiple acini grouped around the termination of each of the many branching ducts. The acini are lined with cuboidal epithelium and the ducts with stratified transitional epithelium. Argentaffin cells have been described in the epithelial lining of the main excretory duct of Bartholin’s gland and the paraurethral glands [35].

These are lined by a single layer of secretory cells.

These glands have a mucinous columnar epithelium, and their ducts are lined by transitional‐type epithelium. Small cysts can occur in the duct.

They are composed of delicate fibrovascular cores lined by bland squamous epithelium that may have a thin layer of keratin. There is no koilocytosis.

The vagina has an outer adventitial coat of fibroelastic tissue by which it is bound to the urethra and anchored to the pelvic walls by the pelvic ligaments. The intermediate coat of circular and longitudinal smooth muscle is intermingled with striated muscle from the pelvic floor. Between the muscular and inner epithelial layers is a layer of loose fibroelastic tissue in which there is an extensive network of venous channels. This venous network, with distension, changes the vaginal walls into erectile tissue and is the probable source of vaginal secretion during sexual intercourse. The inner aspect of the vagina is lined with non‐cornifying stratified squamous epithelium, the cells of which are heavily glycogenated. The vaginal surface of the cervix is covered with stratified squamous epithelium, while the cervical canal is lined by columnar epithelium in which there are numerous mucus‐secreting cells. The squamocolumnar junction may occur at the external os, but more often there is a transformation zone of variable extent situated around the external os.

In addition to keratinocytes there are three other cell types in the epidermis: melanocytes, Langerhans cells, and Merkel cells.

Melanocytes are cells of neural crest origin that produce melanin. They appear as rounded cells with clear cytoplasm and are situated in the basal layer of the epidermis. They convert the amino acid tyrosine to melanin within membrane‐bound organelles called melanosomes. These are then transferred to keratinocytes through the melanocytes’ dendritic extensions. This transfer within the ‘epidermal melanin unit’ protects keratinocyte DNA from damage by ultraviolet radiation and certain toxins.

Melanocytes are also capable of other actions including secreting a number of signal molecules targeting keratinocytes, lymphocytes, fibroblasts, Langerhans cells, mast cells, and endothelial cells. Hormones profoundly influence human melanocyte activity, and there is a marked regional variation in the sensitivity of melanocytes to specific hormones. The vulva and perineum are sites that are very sensitive to hormonal factors.

Langerhans cells are found in the epidermis and are bone‐marrow‐derived dendritic cells, present in all layers of the epidermis. They lack pigment and represent 1–2% of the epidermal cell population and are located mainly in the suprabasal area. An analysis of the distribution of Langerhans cells in healthy tissue of the genital tract showed there were 19 per 100 basal squamous cells in the vulva [36]. They contain characteristic Birbeck granules, shaped like a tennis racquet in their cytoplasm. Each cell possesses five to nine dendritic processes, which extend out in the same horizontal plane.

Langerhans cells are antigen‐presenting cells, taking up the antigen and transporting it to the lymph node. They play an important immunological role in the skin and are involved in the sensitisation and activation of contact allergic dermatitis as well as participating in the immune surveillance of the skin. These immunological functions are particularly important in the lower female genital tract as these sites are exposed to a wide range of antigens. They may be involved in oncogenic HPV infection, and it has been shown that Langerhans cell counts are lower in HIV patients with vulval intraepithelial neoplasia [37].

These cells are found throughout the skin, situated singly or in clusters in the basal layer of the epidermis. The dendritic cytoplasmic processes surround adjacent keratinocytes, and they interact with free nerve endings in the skin. They act as mechanoreceptors for light touch, but may have endocrine and inflammatory functions [38].

The basement membrane zone is a complex area with two layers, the upper lamina lucida and the lower lamina densa. The major components are type IV collagen and laminins with hemidesmosomes, anchoring filaments, and fibrils forming attachment structures. The vulval and vaginal basement membrane zone components are the same as those in non‐genital skin [39].

The dermis lies below the epidermis and above the subcutaneous fat. It has two layers: the papillary dermis and the reticular dermis. The upper papillary dermis projects upwards into the rete ridges and is composed of fine collagen fibres, running at right angles to the surface, together with reticular and elastic fibres. This arrangement supports vascular and lymphatic channels as well as nerve endings. The lower reticular is composed of coarse collagen fibres lying parallel with the surface. Thicker elastic fibres accompany the collagen fibres to prevent it being overstretched. In the perineal area, smooth muscle fibres similar to those seen in the nipple, penis, and scrotum are also present. The vascular and lymphatic plexuses that drain the papillary dermis lie within the reticular dermis, which also contains the nerve fibres associated with the papillary nerve terminals.

1 5 Kreklau, A., Vâz, I., Oehme, F. et al. Measurements of a 'normal vulva' in women aged 15‐84: A cross‐sectional prospective single‐centre study. BJOG. 2018 Dec; 125(13): 1656–1661.

2 6 Lloyd, J., Crouch, N.S., Minto, C.L. et al. Female genital appearance: ‘normality’ unfolds. BJOG. 2005 May; 112(5): 643–646.

3 10 Brodie, K., Alaniz, V., Buyers, E. et al. A Study of adolescent female genitalia: What is normal? J Pediatr Adolesc Gynecol. 2019 Feb; 32(1): 27–31.

4 22 Moyal‐Barracco, M., Leibowitch, M. and Orth, G. Vestibular papillae of the vulva. Lack of evidence for human papillomavirus aetiology. Arch Dermatol. 1990; 126: 1594–1598.

5 30 Day, T., Holland, S.M. and Scurry, J. Normal vulvar histology: Variation by site. J Low Genit Tract Dis. 2016 Jan; 20(1): 64–69.