Dark-colored Lesions: Brown, Blue, Gray, or Black Disorders

Peter J. Lynch

Pigmented lesions are present on the skin of the genitalia in approximately 10% to 12% of women and a slightly smaller proportion of men. The etiologic basis for these pigmented lesions includes physiologic pigmentation, postinflammatory hyperpigmentation, some infections, and benign and malignant neoplasms. The tan, brown, and black colors arise as a result of melanin pigmentation. Melanin pigment is made within cytoplasmic organelles (melanosomes) in melanocytes that lie along the basement membrane of the epithelium. The amount of color in both normal skin and various lesions is determined by several factors: the density of melanocytes, the amount of melanin produced per melanocyte, and the transfer rate of the melanized melanosomes to the 30 or so keratinocytes that surround each melanocyte. The density of melanocytes, surprisingly, does not vary appreciably in people of different racial backgrounds, but it does vary by site. Genital tissue, for instance, has about 50% more melanocytes per unit of area than does truncal skin. The development of increased pigmentation is partially dependent on genetic factors (variability in racial groups) and partly by acquired factors such as ultraviolet light, the presence of inflammation (especially that involving basal layer damage), some kinds of infection (notably HPV infection in the genital and perigenital areas), and, in women, their hormonal state. Increased pigmentation also occurs when there is proliferation in the number of normally melanized keratinocytes (epithelial hyperplasia) and/or when there is an increased retention of normally melanized keratinocytes in the stratum corneum. For a few disorders in this chapter, heme pigment rather than melanin explains the presence of a dark color.

Physiologic Hyperpigmentation

Physiologic hyperpigmentation occurs as symmetrical, flat, smooth-surfaced, asymptomatic darkening of the skin. The most commonly affected sites include the scrotum in male patients and the labia majora and outer edges of the labia minora in female patients (Fig. 9.1). The perianal skin in both genders usually displays some degree of physiologic hyperpigmentation (Fig. 9.2). Appreciable variation in hue occurs across racial groups and also from person to person even within a given racial group. The degree of pigmentation can be so light that it is hardly noticeable or may be so dark as to be almost black in color.

The diagnosis of physiologic hyperpigmentation is made on a clinical basis. The differential diagnosis includes postinflammatory hyperpigmentation, but the latter tends to be patchier and is often seen less symmetrically distributed. If biopsy of physiologic hyperpigmentation is carried out for reasons of concern by either patient or the clinician, increased melanin will be found in both the melanocytes and keratinocytes, which line the basal layer of the epithelium. Genital hyperpigmentation occurs because of the greater density of melanocytes in the genitalia compared to surrounding skin. These areas of hyperpigmentation will darken further under the influence of both endogenous and exogenous sex hormones. This is particularly notable during pregnancy. Darkening will also occur due to the presence of increased melanocytestimulating hormone (MSH) in neonates and in patients with disorders such as Addison disease due to the marked disturbance in pituitary-adrenal axis function.

Treatment is not necessary or even desirable. However, it is worth noting that obsession with anogenital hyperpigmentation has led to the provision of bleaching services by both licensed and unlicensed practitioners.

Acanthosis Nigricans

The prevalence of acanthosis nigricans (AN) varies with skin color and is present in about 13% of African Americans, 5% of Hispanics, and 1% of Caucasians (1). Prevalence also varies with obesity and obesity-related insulin resistance (2). Acanthosis nigricans was an uncommon disorder 50 years ago, but it is found much more often in recent years due to the marked increase of obesity especially in children. In a 2012 Brazilian study of children and adolescents being cared for in an obesity center, 58% and 43% of the
participants had acanthosis nigricans and insulin resistance, respectively (3). While acanthosis nigricans is most often found in those who are obese, it also occurs with various endocrinopathies, with malignancies, and with the use of a few medications such as niacin.

FIG. 9.1. Physiologic hyperpigmentation of the vulva is most marked on the labia minora and, sometimes, on the posterior fourchette and perineal body.

Acanthosis nigricans appears as poorly demarcated light brown to dark brown lesions around the neck, in the axillae, and in the crural folds (Figs. 9.3 and 9.4). Rarely, it develops in other folded areas of the body and on the genitalia. The background of hyperpigmentation may be flat, but characteristically, there are elevated linear ridges running parallel to one another. The surface of the lesions is slightly “bumpy” and is often velvety or very slightly rough on palpation. Acanthosis nigricans is asymptomatic or mildly pruritic but is very troubling to the patient because it suggests the appearance of dirty skin. The diagnosis is established clinically. The major disorder to be considered in the list differential diagnoses is lichen simplex chronicus in which postinflammatory hyperpigmentation has occurred.

FIG. 9.2. Perianal skin very often manifests poorly demarcated hyperpigmentation of physiologic hyperpigmentation.

FIG. 9.3. Acanthosis nigricans is manifested by hyperpigmentation in skin folds, often with a velvety or linear appearance that mimics lichenification. Skin tags often accompany acanthosis nigricans.

Treatment of acanthosis nigricans is problematic. Topical retinoids and trichloroacetic acid peels can be tried, but often, the side effects are perceived as worse than the disorder. However, the appearance can be improved through weight loss or treatment for any associated endocrinopathy. Evaluation of patients with AN is usually desirable because of the frequently associated presence of insulin resistance, abnormal glucose homeostasis, hypertension, and elevated cholesterol (1). Very rarely, acanthosis nigricans is associated with the development of malignancy, especially that involving the gastrointestinal
tract. This association should be considered in those adults who lack endocrinopathy, are nonobese, and/or have a recent history of unintentional weight loss.

FIG. 9.4. The papillomatous appearance of acanthosis nigricans is generally found in areas of friction, such as this man’s perineum, and in obese patients who are naturally dark complected.

Postinflammatory Hyperpigmentation

Inflammation affects melanocytes in two ways. While severely damaged melanocytes discontinue the production of melanin with resulting hypopigmentation, mildly damaged melanocytes react with increased melanin production and hyperpigmentation. Postinflammatory hyperpigmentation develops at the site of previous inflammation. Tanning after mild sunburn can be considered as an example of postinflammatory hyperpigmentation. Inflammation may be an inherent component of a skin disease, or inflammation may develop at the site of trauma such as might occur following incessant scratching, the use of liquid nitrogen or trichloroacetic acid (Fig. 9.5). Postinflammatory hyperpigmentation is clinically recognized as light to dark brown, nonpalpable macules and patches occasionally displaying hues of gray, blue, or black. The distribution, location, and intensity of hyperpigmentation are dependent on the underlying cause.

Diseases such as lichen sclerosus and lichen planus, in which inflammation preferentially damages the basal layer of the epithelium, are likely to be associated with darker pigmentation than occur with other inflammatory disorders (Figs. 9.6 and 9.7). Not surprisingly, patients with darker constitutive skin are more likely to develop exaggerated postinflammatory hyperpigmentation. Similarly, because normal genital color is generally darker than surrounding skin, inflammation in genital tissue is particularly likely to cause postinflammatory hyperpigmentation.

FIG. 9.5. Postinflammatory hyperpigmentation can occur after trauma, as seen in this patient’s prurigo nodules of excoriated, thickened papules produced by chronic picking.

FIG. 9.6. Lichen sclerosus sometimes produces poorly demarcated hyperpigmentation owing to basal layer damage and resulting phagocytosis of melanin granules by macrophages in the dermis.

A history of prior trauma or previous inflammation is an important diagnostic clue, but sometimes, such a history cannot be evoked. This is particularly true in anogenital lichen planus and lichen sclerosus where extraordinarily long-lasting hyperpigmentation may
first be noted a very long time after any clinical evidence of inflammation has resolved. In some instances in which a history of previous inflammation cannot be obtained, a biopsy will be necessary to confirm a diagnosis of postinflammatory hyperpigmentation. This is particularly true for pigmented macules or patches where the pigment is variable in density or where gray or black hues are present (See the sections on genital melanosis and melanocytic nevi in this chapter).

FIG. 9.7. Lichen planus is a common cause of postinflammatory hyperpigmentation; both active, red papules are evident as well as brown pigmentation left by resolving lesions.

Because postinflammatory hyperpigmentation usually resolves over several months, no treatment is necessary. However, the presence of pigmentation sometimes obscures continuing low-grade inflammation. Thus, if the pigmentation persists longer than expected, biopsy should be obtained to determine whether or not subclinical inflammation is present. If present, anti-inflammatory treatment, such as topical steroids, should be administered. Topical fading agents, such as hydroquinone, may improve pigmentation located superficially in the epidermis but are of no use for pigment lying deeper in dermal melanophages.

Seborrheic Keratoses

Seborrheic keratoses are extremely common, benign growths. Most individuals over the age of 40 have at least one or two lesions, and often 50 to 100 may be present. Most are located on the trunk, but occasionally, they are noted on the proximal limbs and anogenital area. Seborrheic keratoses present as sharply marginated, square-shouldered, tan, brown, or black papules 10 to 15 mm wide and 2 to 10 mm tall (Figs. 9.8 and 9.9). These attributes contribute to a characteristic “stuck on” appearance. The surface often contains visible scale and is usually rough on palpation. However, in some instances, the surface has a smooth “waxy” feeling simulating a drop of candle wax on the surface of the skin. However, in these smooth lesions, the presence of scale can be identified if the surface is gently scraped with a blade held perpendicular to the top of the lesion.

FIG. 9.8. Seborrheic keratoses vary from tan or even skin colored to dark brown, but they nearly always have a slightly rough or “warty” surface.

FIG. 9.9. Seborrheic keratoses mimic both melanocytic nevi and genital warts.

The presence of scale is a very helpful point in distinguishing seborrheic keratoses from those of nevi, lentigines, and melanomas. Small, characteristic surface pits may be found when magnification is used in the course of examination. Specifically, in making this differentiation, dermoscopy may be helpful (4). Genital seborrheic keratoses may be quite difficult to differentiate from both pigmented genital warts and HPV-related intraepithelial neoplasia. The number of lesions present is a helpful clue. Genital seborrheic keratoses are generally solitary, whereas HPV-related lesions are almost always more numerous. Seborrheic keratoses may also resemble pigmented basal cell carcinomas. Because differentiation of seborrheic keratosis from all of these lesions is so important, most genital seborrheic keratoses should be biopsied.

The cause of seborrheic keratoses is unknown, but frequent familial patterns regarding age at onset and number of lesions suggest that both genetic and aging factors play a role. It is of considerable interest that mutations in oncogenes are found in 80% of seborrheic keratoses (5). These same mutations are found in other lesions that behave in a malignant fashion, whereas malignancy essentially never develops in seborrheic keratosis. The reasons for this are not completely known, but additional discussion of this topic can be found elsewhere (5,6). Much controversy exists whether human papillomavirus (HPV) plays any role in the development of anogenital seborrheic keratosis, but we and others believe it does
not and that the controversy arises simply because of the difficulty in clinically differentiating seborrheic keratosis from anogenital warts and HPV-related intraepithelial neoplasia (7).

Biopsy is desirable in any instance of uncertainty regarding the diagnosis. No therapy is necessary for clinically typical, or histologically proven, seborrheic keratoses. Lesions that are irritated by clothing and those that are particularly bothersome to the patient may be treated with liquid nitrogen or with shave excision.

Pigmented Warts

Genital warts of the flat-topped type are frequently tan, brown, or black in color (Figs. 9.10 and 9.11). These lesions are covered along with other morphologic types of warts in Chapter 5.

Genital Intraepithelial Neoplasia

HPV-related vulvar, penile, and scrotal intraepithelial neoplasia is frequently tan, brown, or black in color (Figs. 9.12, 9.13 and 9.14). These conditions are primarily discussed in Chapter 5.

Pigmented Basal Cell Carcinoma

Basal cell carcinomas are normally skin colored, but a small proportion contains sufficient melanin to be at least partially brown, blue, or black in color (Fig. 9.15). These lesions are primarily covered in Chapter 5.

FIG. 9.10. This solitary pigmented wart is indistinguishable clinically from a seborrheic keratosis; the diagnosis was made by a biopsy.

FIG. 9.11. Individuals who have naturally dark complexion typically exhibit brown warts.

Angiokeratomas

Genital angiokeratomas are usually light to dusky red in color, but those occurring on the vulva are sometimes blue, purple, or black (Figs. 9.16 and 9.17). These lesions are primarily covered in Chapter 7.

Kaposi Sarcoma

The nodules and plaques of Kaposi sarcoma occurring on the trunk and genitalia are usually medium to dusky red in color. Less often, they are darker in color and may have
blue, purple, or even black hues (Fig. 9.18). This neoplasm is primarily discussed in Chapter 5.

FIG. 9.12. Flat brown warts in a person with light skin are likely to represent warts with atypia. These warts showed high-grade squamous intraepithelial lesions (HSIL), previously called vulvar intraepithelial neoplasia 3 (VIN 3) on biopsy. Some of these have evolved into the large invasive squamous cell carcinomas present on the perineum and vulva.

FIG. 9.13. These flat-topped tan papules showed HSIL on biopsy. The brown color in a pale person, flat morphology, and clustered pattern prompted the biopsy.

Genital Varicosities

Varicosities may be small or large. Larger lesions are usually blue in color (Figs. 9.19 and 9.20). Large varicose veins occur on the vulva with some frequency in pregnant women and they may or may not resolve following parturition (8,9). Varicosities are much less common on the penis and scrotum. Very small diameter dilated vessels (“spider veins”) are more likely to be dusky or dark red. Such telangiectatic vessels occur commonly on the scrotum. Often tiny angiokeratomas overly these small dilated red telangiectatic vessels. Varicosities are identified by their disappearance following compression with a glass slide (diascopy). No treatment is ordinarily necessary, but bleeding following trauma may require electrosurgery or even excision.

FIG. 9.14. Not all flat or slightly elevated, hyperpigmented HPV-associated lesions are dangerous. A biopsy simply showed benign genital warts.

FIG. 9.15. Although basal cell carcinomas are most often skin colored or pink, these can sometimes show either black speckling or bluegray discoloration as seen in the woman’s multiple basal cell carcinomas that appeared following radiation therapy.

Genital Melanosis (Lentiginosis)

Clinical Presentation

Genital melanosis and genital lentiginosis have been used interchangeably by clinicians, but, strictly speaking, the latter term is only applicable to those lesions that demonstrate a lentigo-like histologic pattern on biopsy. Since
this is not present in all cases, we prefer the term genital melanosis. Pigmented lesions of melanocytic type are common on the genitalia with a prevalence estimated to be about 10% to 15% in both men and women (4,10). In women, about 60% to 70% of all vulvar pigmented lesions represent vulvar melanosis (4,11), and this is likely true for men as well (4).

FIG. 9.16. Angiokeratomas are vascular, shiny, dome-shaped papules, but they often are such a dark purple that they appear black.

FIG. 9.17. When solitary, an angiokeratoma should be differentiated from a nodular melanoma; this is an easy distinction with evaluation with a dermatoscope. Fortunately also, this man exhibits surrounding more subtle lesions.

Genital melanosis consists of nonpalpable, nonelevated macules and patches of pigmentation (Figs. 9.21, 9.22 and 9.23). This pigmentation occurs most often on mucous membranes or modified mucous membranes, but it can arise on keratinizing skin as well. Genital melanosis is particularly likely to arise from a background of lichen sclerosus (Fig. 9.24). Lesions of melanosis may be solitary or multifocal with the latter occurring more frequently. There is a great deal of variation in the size and color of the pigmentation. Lesions may be as small as 5 mm, but most are considerably larger with diameters up to 2 cm. Asymmetry in distribution is common, and the configuration is at times quite angular. Pigmentation may be tan, brown, blue, or black; often, there is considerable pigment variegation within the lesions. The borders may be either poorly or sharply marginated.
In men, given the ready visibility of the penis, there is commonly a history of long duration with little or no change in appearance, but for women, the duration is often unknown. In women, the pigmented patches are most often found on the labia minora (11). The labia majora are less frequently involved, and vaginal and perineal lesions are only rarely encountered. In men, most lesions occur on the glans and inner aspects of the prepuce, but penile shaft and urethral meatus involvement is possible (4).

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