Zlatko Marusic and Eduardo Calonje Benign lesions can develop from all layers of the skin and subcutis, and the vulva may be affected by these as at other sites. However, there are also specific lesions that affect the vulva. The entities of aggressive angiomyxoma and desmoid tumours, while not malignant, are locally aggressive and are therefore discussed in Chapter 45. These are the most common cysts found in the vulva, as they are elsewhere in the skin. They are more common in adults, but are also reported in adolescents and children [1]. Clitoral epidermal inclusion cysts are known to occur as a complication of female genital mutilation and may present many years later [2]. However, they are also reported in the absence of trauma [3, 4] and can be mistaken for clitoromegaly, especially in younger patients. They usually occur on the inner and outer labia majora and may be single or multiple (Figure 38.1). They present as painless nodular swellings up to 1 cm in diameter but can be larger. They are frequently tethered to the overlying epidermis, which may have a depression or central pore connecting with the lumen. They are lined by bland orthokeratotic squamous epithelium and filled with laminated keratin. Sebaceous differentiation may be present. Rupture of a cyst may lead to inflammation with a foreign body giant cell response. No treatment is needed, and indeed, if there are multiple cysts, excision can cause significant scarring. If large or symptomatic, then simple enucleation can be performed. Mucinous cysts usually occur in adults but have also been described in adolescents [5]. Figure 38.1 Epidermoid cysts both labia majora. Several angiokeratomas are also seen. They are usually single, but may be multiple, and range from a few millimetres to 3 cm in size. They are sometimes pedunculated. They are usually seen on the inner labia minora or vestibule, and it is postulated that they arise from the obstruction of the minor vestibular ducts [6] or the embryological remnants of the urogenital sinus [7]. However, cases are described where there are multiple cysts on the keratinised side of Hart’s line, which may be due to obstruction of the mucinous glands by keratin [8]. The cysts are lined by a single cell layer of bland columnar (endocervical)‐type mucinous epithelium (Figure 38.2). Focal squamous metaplasia, reserve cell hyperplasia, and ciliated cells may be present, but there is no myoepithelial cell layer or associated rim of smooth muscle. They can be excised if troublesome. The anogenital mammary‐like glands seen in the vulva may undergo cystic dilatation, and mimic fibrocystic disease seen in the breast [9]. Small cystic lesions are seen, but they do not have specific diagnostic features clinically. The histological appearance is similar to fibrocystic change of the breast. There is dilation of glands with occasional apocrine metaplasia. In the absence of apocrine metaplasia, the cysts are lined by an outer myoepithelial cell layer and an inner layer of secretory cells that have luminal snouts. The secretory cells are positive for oestrogen and androgen receptors, and are often positive for progesterone receptors. However, metaplastic apocrine epithelium in these cysts is negative for oestrogen and progesterone receptors, and the anogenital gland origin of the cyst may be recognised only by a transition from native to metaplastic epithelium or the presence of typical anogenital glands and absence of apocrine glands in the region of the cyst [10]. Figure 38.2 Mucinous cyst lined by a single layer of columnar endocervical‐type endothelium. The canal of Nuck is a pouch of peritoneum that extends into the labium majus, and if it is not obliterated, cysts can develop. They are seen in the upper labia majora and are frequently associated with an inguinal hernia. [11]. They are lined by bland mesothelial cells. The cysts can be excised, but assessment with imaging including the lymphatics pre‐operatively is recommended [12] as they can be extensive. There are cysts that fail to fit into any of the well‐described types. These tend to be less than 1 cm in diameter and have no connection with the overlying epidermis or adnexal structures. The cysts may be lined by bland ciliated, sebaceous‐like, or apocrine‐like cells. Squamous metaplasia may be present. These benign cysts should be reported as a ‘benign cyst of probable adnexal origin’. Fibroepithelial polyps are common mesenchymal lesions that range in size from small skin tags to huge tumour‐like lesions. They may be associated with pregnancy. They present as flesh‐coloured sessile or pedunculated polypoid lesions usually arising from the labia majora. Huge lesions are described, and infection can be a risk in these situations [13]. They have a vascular connective tissue stroma composed of cells derived from the subepithelial stromal cells that line the lower female genital tract from the cervix to the labia minora. The stroma is usually hypocellular and composed of mononucleated stellate cells and multinucleated cells with long tapering cytoplasmic processes and merges with the adjacent non‐polypoid stroma. Approximately half of the tumours are hypercellular, with the cellularity being greatest at the centre of the polyp [14]. Atypical cells may be present, particularly among the multinucleated cells, and there may be high mitotic counts or atypical mitoses. The overlying squamous epithelium is usually acanthotic (Figure 38.3) and may be hyperkeratotic or parakeratotic. Simple surgical excision is needed if large. Small skin tags can be treated with cryotherapy. They can recur, although this is uncommon. Seborrhoeic keratoses are extremely common lesions which occur in most people over the age of 50. They are usually found on the trunk and limbs. They form warty proliferations that appear stuck onto the surface, are usually pigmented and may have a waxy appearance owing to extruded keratin (Figure 38.4). Large lesions can be mistaken for warts [15] or tumours. They can undergo change and become irritated where the appearance can be darker and more nodular. These are referred to as inverted follicular keratoses, and this entity has been reported on the vulva [16]. The melanoacanthoma variant, which generally occurs in older people, has also been described affecting the vulva in a 27‐year‐old [17]. Figure 38.3 Fibroepithelial polyp with mildly cellular stroma and overlying bland epithelium. Figure 38.4 Seborrhoeic keratose showing stuck on waxy papules. The important differential diagnosis is pigmented intraepithelial neoplasia, and this is very difficult to distinguish clinically. Biopsy is needed for atypical lesions. They are composed of papillary proliferations of small bland basaloid cells that resemble those of normal squamous epithelium and have delicate fibrovascular cores. Melanin pigment is frequently present throughout the proliferation, and the surface is usually hyperkeratotic. Mitoses are absent or rare. Commonly, laminated keratin in apparent cystic spaces, ‘keratin tunnels’, is present (Figure 38.5). When irritated, there may be prominent inflammation with mild nuclear atypia and a more squamoid appearance. Unlike squamous carcinoma and vulval intraepithelial neoplasia, mitotic figures remain confined to the basal layers, and atypical mitoses are absent. The proliferation retains its ‘pasted‐on’ appearance, there is an absence of atypical parakeratosis, and residual keratin tunnels may be present. Occasionally, the proliferation may be ‘inverted’ with pushing rounded nests of bland basaloid cells with keratin tunnels that may resemble a basal cell carcinoma. However, unlike basal cell carcinomas, the surface epithelium from which the nests originate is a full thickness of bland basaloid squamoid cells rather than atypical basaloid cells limited to the basal layer, while mitotic figures are rare or absent. Sometimes, early lesions are described as squamous papillomas and are composed of papillary acanthotic change with hyperkeratotic or parakeratotic proliferations of bland squamous epithelium with normal maturation. Figure 38.5 Seborrhoeic keratosis composed of bland basaloid cells and keratin tunnels. Treatment is only required if they are symptomatic. For smaller lesions, cryotherapy will be effective, but larger, thicker lesions may require curettage or excision. Verruciform xanthomas are uncommon lesions that usually occur in the oral cavity. Lesions of the vulva are uncommon but typically occur in women of reproductive age. They are much more common in men, and in one review of 183 patients with genital verruciform xanthoma, only 29 were female [18]. It presents as one or more papillary or cauliflower‐like lesions that are usually clinically diagnosed as warts. They may occur in the context of inflammatory dermatoses such as lichen sclerosus [19] or trauma [20]. There are invaginated areas of confluent hyperkeratosis with parakeratosis and intracorneal neutrophils. The underlying papillary dermis contains characteristic collections of foamy histiocytes that may be cuffed by a pseudoepitheliomatous hyperplastic elongation of the rete pegs (Figure 38.6). Treatment is by local excision. One case of recurrence 8 years after ablation with the CO2 laser is described [21]. Figure 38.6 Verruciform xanthoma with papillary proliferations. These rare lesions are benign tumours of epidermal keratinocytes. The condition may occur sporadically or be genetically inherited and associated with oral lesions. The lesions form white hyperkeratotic plaques on the vulva, which may be pruritic [22]. They may be multiple [23] or linear [24]. Histologically, there is a cup‐shaped invagination of broad rete pegs of hyperkeratotic epithelium with well‐circumscribed borders. Surface papillae are present, but they lack the typical parakeratosis of warts. The basal epithelium lacks atypia but may have increased mitotic activity relative to the adjacent non‐involved epithelium. Abnormal mitoses are absent. Dyskeratotic cells are present in the overlying maturing epithelium, and the surface granular cell layer contains coarse keratohyalin granules and corps ronds and dense eosinophilic globoid bodies that are the remnants of the dyskeratotic cells. Although binucleated cells may be present, well‐developed warty koilocytes are absent. No treatment is needed if they are asymptomatic, but cryotherapy or other ablative techniques are effective. The anogenital mammary‐type glands are described in Chapter 2. These are very common benign lesions in the breast. Histologically identical lesions are seen in the vulva arising from the anogenital mammary‐type glands of the vulva. Vulval fibroadenomas present as painless subcutaneous lumps. They may be multiple and seen in association with breast fibroadenomas [25]. They can suddenly increase in size with lactational changes after delivery [26]. Like their mammary counterpart, they are positive for oestrogen and progesterone receptors and may undergo apocrine metaplasia. A proliferation of anogenital glands may lead to a fibroadenoma that has a histological appearance identical to that of its counterpart in the breast and may undergo lactational change. In cases with prominence of fibrous stroma (stromal overgrowth) or stromal hypercellularity, the histology is identical to that of a phyllodes tumour. However, no clinically malignant phyllodes‐like tumours have been described in the vulva. Treatment is excision but they can recur, and this is most likely to happen with an increased tumour size and incomplete excision [27]. These are the vulval counterpart of the mammary intraductal papilloma. In one series of 189 vulval adnexal lesions, hidradenoma papilliferum (HP) was the commonest type seen [28]. HP tends to occur during the reproductive years and menopause. They usually arise in the interlabial sulcus (Figure 38.7) or in the labia adjacent to the sulcus or in the perineum, which are sites of the anogenital mammary‐like glands [29, 30]. They are often long‐standing with no change in size, but rapid growth can occur. They are solitary, firm, mobile nodules that may be red or blue in appearance and rarely enlarge over 2 cm. Cystic change may be apparent. They are usually asymptomatic, but if they do enlarge, the surface may ulcerate and bleed on contact. Variable dermoscopic features are described [31]. Histologically, there are well‐formed non‐encapsulated subepithelial nodules of acinar–papillary proliferations lined by an outer layer of myoepithelial cells [32, 33], and an inner layer of bland to mildly atypical amphophilic to eosinophilic cuboidal to columnar cells with secretory snouts (Figure 38.8). Rarely, an opening onto the surface may be present. The fibrous stroma is usually scant but may be prominent. Mitotic figures can rarely be seen, and atypical mitotic figures are absent. Apocrine metaplasia is frequent (Figure 38.9) [34]. The tumours are positive for cytokeratin 7 and androgen receptor [33], and unlike most tumours of sweat gland origin, are negative for epidermal growth factor (EGF) receptor protein. The areas lined by cuboidal to columnar cells are positive for oestrogen and progesterone receptors and are usually negative for gross cystic disease fluid protein (GCDFP), whereas areas of apocrine metaplasia are negative for oestrogen and progesterone receptors and positive for GCDFP [33]. This profile closely resembles that of the non‐neoplastic anogenital glands. Figure 38.7 Hidradenoma papilliferum. Small nodule in right interlabial sulcus. Figure 38.8 Hidradenoma papilliferum with variable sized tubular glands.
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Benign Vulval Tumours
Benign cysts
Epidermoid (tricholemmal, sebaceous, keratinous, epidermal inclusion) cysts
Pathophysiology
Clinical features
Histological features
Complications
Management
Mucinous cysts
Clinical features
Histological features
Management
Anogenital gland cysts
Clinical features
Histological features
Cyst of canal of Nuck (Mesothelial cyst)
Clinical features
Histological features
Management
Benign cysts of probable adnexal origin
Benign tumours of the epithelium
Fibroepithelial polyps
Clinical features
Histological features
Management
Seborrhoeic keratoses
Clinical features
Differential diagnosis
Histological features
Management
Verruciform xanthoma
Clinical features
Histological features
Management
Epidermolytic acanthoma (epidermolytic hyperkeratosis)
Clinical features
Histological features
Management
Benign tumours of the anogenital mammary‐type glands
Fibroadenomas
Clinical features
Histological features
Management
Hidradenoma papilliferum
Clinical features
Histological features
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