Melanocytic Lesions of the Vulva

Clinical Features

Genital melanosis, also known as vulvar lentiginosis and vulvar melanotic macules, is a benign lesion characterized by macular pigmentation that can involve cutaneous or mucosal sites. It accounts for most pigmented vulvar lesions (≈68%) in women of reproductive age, and the median age at presentation is 40 to 44 years. Lesions are often clinically concerning because they are frequently large, with irregular borders. The macules may be single or multiple, with predilection for mucosal surfaces, including the vulva, vagina, and cervix, rather than hair-bearing skin ( Fig. 8.1A and B ). Typically, pigmentation increases slowly over time. Vulvar melanosis has been associated with hormonal factors after reported cases coinciding with the use of oral contraceptives and the postpartum period. Vulvar melanosis has also been associated with lichen sclerosus (see Fig. 8.1C ) and human papillomavirus (HPV) infection.

In children, the possibility of a genodermatosis should be considered (e.g., Peutz-Jeghers syndrome, Dowling-Degos disease). Laugier–Hunziker syndrome (idiopathic lenticular mucocutaneous pigmentation) is a disorder characterized by genital lesions associated with oral pigmentation. Rarely, Carney's complex may present with lentigines in the genital skin and mucosa.

Histopathology

Biopsy of genital melanosis shows increased pigmentation of basal keratinocytes, predominantly affecting the tips of the rete to variable degrees ( Fig. 8.2 ). In many cases, abundant melanin is present within melanophages in the papillary dermis or superficial lamina propria, so-called pigment incontinence. Some authors restrict use of the term genital melanosis to lesions that do not show increased numbers of melanocytes. In contrast, the term genital lentiginosis is applied to similar lesions that are associated with increased numbers of melanocytes. The terminology used is of nosologic but not practical importance. Melanocytic atypia is not a typical feature and, if present, particularly when accompanied by a pagetoid spread of melanocytes, should raise concern for a significant precursor lesion or even melanoma in situ.

Clinical Features

Typical intradermal and compound nevi can be seen in the vulva and are similar to those at other sites ( Fig. 8.3 ). The genital-type nevus (GTN) often shows distinctive histologic features that are also seen in other sites characterized by redundant skin. For this reason, the term flexural-type nevus is sometimes applied to this variant. Other regions where flexural-type nevi are commonly encountered include the axillae, umbilicus, inguinal creases, scrotum, and perianal areas. Familiarity with flexural-type nevi is of great importance because they may be associated with histologic features that raise the possibility of, or may be confused with, melanoma.

It is estimated that the prevalence of vulvar nevi is approximately 2.3%, accounting for approximately 20% of all pigmented lesions of the vulva. GTNs comprise approximately 5% of vulvar nevi. They are most common in young women but may also be seen in young girls and older women. In adults, vulvar nevi are generally encountered on premenopausal women, with an estimated median age range of 28 to 33 years of age for typical nevi and 17 to 26 years for GTN. Compared with common nevi occurring in the vulva, GTNs are more frequently located on the labia minora and equally affect genital hair-bearing skin and mucosal surfaces in adults. In children 10 years of age or younger, GTNs are more common in mucosal sites.

GTNs are often heavily pigmented, irregular, vary in size from a few millimeters to 1 cm or more in their greatest dimension, and may be concerning clinically. They may occur anywhere on the vulva, including the labia majora, labia minora, and clitoris.

Histologic Features

As noted earlier, GTNs can be a source of considerable diagnostic difficulty because they are less frequently encountered than common dermal and compound nevi. Consequently, many surgical pathologists are not familiar with their unique histologic features. When atypical features are present, they may be confused with melanoma ( Table 8.3 ).

GTNs may be junctional or compound. At scanning magnification, they may be symmetric or asymmetric and often have a papillomatous appearance ( Fig. 8.4A ). The junctional component is usually lentiginous and nested (see Fig. 8.4B ). The junctional nests are often large, surrounded by a retraction artifact, and are frequently irregularly placed at the sides of a rete (not a typical feature of nevi at nonflexural sites), as well as rete tips ( Fig. 8.5 ). A common feature is the presence of transepidermal elimination of nests of melanocytes; however, frank intraepidermal pagetoid spread of individual melanocytes is not a prominent feature (see later). In our experience, when pagetoid spread is present, it is usually limited to small numbers of cells and restricted to the lower layers of the epidermis.

The junctional nevus cells are epithelioid and may exhibit cytologic atypia, such as nuclear enlargement and nucleolar prominence. Hyperchromatism is sometimes a feature. Cytologic atypia, if present, is usually seen only in a subpopulation of cells. When it involves a large fraction of melanocytes, concern for melanoma should be raised.

If a dermal component is present, it shows features similar to that of non-GTNs. In other words, it is the architectural features of the junctional component that allow distinction of GTNs from common compound nevi. The dermal component shows maturation with depth. As with the junctional component, however, the dermal component may show cytologic atypia in the superficial component.

Distinction between severely atypical genital nevi and melanoma can, in some cases, be challenging. Expansile dermal nests with diffuse cytologic atypia, lack of maturation with depth, significant pagetoid spread of intraepidermal melanocytes, effacement of the epidermis, conspicuous mitoses, and asymmetry should all prompt concern for melanoma. A potential diagnostic pitfall is the presence of concurrent lichen sclerosus and GTN because the presence of lichenoid inflammation, sclerosis, and pigment incontinence may mimic regression of melanoma. It is important to remember that melanoma of the vulva is usually seen in older women. Studies have shown that in contrast to melanoma of nongenital sites, which has a peak incidence in early to middle adulthood, vulvar melanoma has its peak incidence around the sixth decade of life. Therefore, one should approach the diagnosis of melanoma with caution in young patients and, similarly, the diagnosis of atypical nevus in older women should be rendered with caution. Nevertheless, vulvar melanoma may occur in the young, and nevi are certainly encountered in older women.

The biologic potential of GTNs has not been carefully studied. For this reason, it is recommended that lesions with significant atypia be completely excised. Although there may be some histologic overlap between dysplastic and vulvar nevi, the former is characterized by elongation of the rete ridges and a more prominent lentiginous growth pattern of junctional melanocytes. Stromal changes that favor dysplastic nevus include eosinophilic and lamellar fibrosis of the papillary dermis and a variable mononuclear inflammatory cell infiltrate.