Skin cancer melanoma picture

Hyperpigmentation usually can be traced to the presence and activity of melanocytes. Part I of this two-part article presents a suggested approach to patients with increased pigmentation. Part II continues the review of conditions associated with hyperpigmentation.

New, Changing, or Symptomatic Localized Lesions

A localized hyperpigmented or irregularly pigmented lesion that is new in onset, arises within a congenital nevus, or causes pain or itching could be a malignant melanoma (Figures 1 through 3). The American Cancer Society has developed useful guidelines for identifying suspicious nevi (Table 1). (1) [Evidence level C, consensus/expert guidelines]

When possible, suspicious lesions should be excised totally for pathologic evaluation. If size or location precludes complete excision, incisional biopsy (usually punch biopsy) is performed. (2)

Seborrheic keratoses are localized, benign, hyperplastic, hyperpigmented lesions that may mimic melanomas. The hyperpigmentation is associated with hyperplasia of melanocytes. (3) Experienced physicians usually can differentiate seborrheic keratoses based on their sharp borders; tan, brown, or black color; and typical appearance. These lesions have a "stuck-on" appearance, with a surface that is rough and craggy (Figure 4, left) or smooth with small keratin "pearls" (Figure 4, right). (4)

If seborrheic keratoses are symptomatic or there is a question about possible malignancy, the lesions should be removed and sent for pathologic evaluation.

Acanthosis Nigricans

Acanthosis nigricans, usually related to insulin resistance or obesity, ranges in appearance from a thickened, velvety brown streaking to a leathery, verrucous, papillomatous lesion (Table 2). The condition commonly occurs on the neck or in skin folds (e.g., in the axilla, under the breast, at the belt line, in the groin), but it may develop in other parts of the body. Patients with this condition may complain that they have a "dirty area" that cannot be cleansed (Figure 5).

Microscopically, acanthosis nigricans is characterized by an increased number of melanocytes, with papillary hypertrophy and hyperkeratosis. (5) Associated hypertrophy and hyperkeratosis cause acanthosis nigricans to be palpable rather than macular.

It is important for physicians to recognize acanthosis nigricans, because the condition can be associated with insulin resistance (as occurs in type 2 diabetes and polycystic ovary syndrome), obesity and, occasionally, malignancy. Type 2 diabetes is increasing in incidence in the United States, especially among black and hispanic children; 60 to 92 percent of these children have acanthosis nigricans. (6) According to one study (7) that compared 50 children with type 2 diabetes and 50 children with type 1 diabetes, acanthosis nigricans was present in 86 percent of the children with type 2 diabetes but in none of the children with type 1 diabetes. (7) [Evidence level B, retrospective cohort study]

If a patient rapidly develops acanthosis nigricans, especially on the palms or soles, occult malignancy is a possibility. A thorough physical examination, a review of systems, a complete blood count, fecal occult blood testing, and chest radiography should be considered if the patient does not fit the typical clinical pattern of insulin resistance. (8) [Evidence level C, consensus/expert guidelines] Adenocarcinomas are the most common malignancies found in patients with acanthosis nigricans; the tumors are most often present in the stomach (60 percent), followed by the colon, ovary, pancreas, rectum, and uterus. (9)

Treatment of acanthosis nigricans is directed at the underlying cause, rather than the appearance of the skin. If present, insulin resistance should be managed appropriately. Screening for hypercholesterolemia and coronary artery disease may be appropriate, depending on the clinical picture.

Melasma

Pregnancy or the use of hormones (e.g., oral contraceptive pills) can cause melasma, a localized facial hyperpigmentation (Figure 6). Melasma may be seen in patients who take phenytoin (Dilantin). While melasma may regress after pregnancy, it may increase with each subsequent pregnancy and become quite obvious. Because of the facial location, melasma may be quite disturbing to patients.

Frequently called the "mask of pregnancy," melasma (chloasma) differs from the ruborous glow of pregnancy. Histologically, women who have this condition develop an increased number of melanocytes, with the deposition of additional melanin and a background of solar elastosis, typically on the cheeks, forehead, and upper lip. (10) Examination using a Wood's light in a darkened room demonstrates enhanced contrast if hyperpigmentation affects the epidermal layer of skin. (11)

Patients with hyperpigmentation of the superficial epidermal layer who desire treatment may attempt a trial of bleaching agents after patch testing elsewhere on the body to confirm low levels of inflammation. Use of bleaching agents on inflamed skin could lead to postinflammatory changes and further hyperpigmentation.

Tretinoin 0.1 percent (Retin-A) cream and hydroquinone (Eldoquin Forte), a bleaching agent available in 2 to 4 percent creams and gels, have been the mainstays of topical treatment. Combining tretinoin and hydroquinone (applied at different times during the day) can potentiate the effect.

A new medication that contains tretinoin, hydroquinone, and fluocinolone acetonide (Tri-Luma) has been effective in the treatment of melasma. In a company-sponsored, double-blind, randomized controlled trial of the triple-combination agent, 77 percent of patients showed complete or nearly complete clearing of melasma, compared with 47 percent for hydroquinone and tretinoin, 42 percent for fluocinolone acetonide and hydroquinone, and 27 percent for tretinoin and fluocinolone acetonide. (12) [Evidence level B, lower quality randomized controlled trial] The triple-combination agent should be applied daily, 30 minutes before bedtime. Azelaic acid (20 percent), kojic acid formulations, and alpha-hydroxy acids also have been useful in the treatment of melasma. (13)

Side effects of all topical treatments include allergic and contact dermatitis, depigmentation of surrounding normal skin, and postinflammatory hyperpigmentation. Tretinoin alone or combined with hydroquinone and fluocinolone acetonide should not be used during pregnancy.

If no increase in contrast is seen with use of the Wood's light, the deeper dermal tissues usually are involved, and bleaching agents will not help. (11) Laser therapy may be used for superficial epidermal or deeper dermal melasma, but strict avoidance of sun exposure is important to prevent recurrence. (14) [Evidence level C, expert opinion]

Diabetic Dermopathy

Diabetic dermopathy (pigmented pretibial papules) develops in up to 70 percent of patients with diabetes. (15) This condition usually affects the skin of the anterior tibial area, where it starts as a papular pink or brown eruption and progresses to a macular, sometimes confluent, brown dermatitis, with the coloration caused by hemosiderin deposition (Figure 7). The exact cause of the lesions is unknown.

The lesions of diabetic dermopathy may resolve spontaneously, even as new lesions arise. Treatment should focus on the patient's diabetes. No treatment for the asymptomatic cutaneous lesions is effective or recommended. (16)

Tinea Versicolor

While tinea versicolor is not truly a hyperpigmentation disorder, it is included in this review because affected skin on the trunk may appear darker than normal. Tinea versicolor rarely occurs until after adolescence, when production of sebum increases, especially in the skin of the anterior trunk and back. The increased sebum production allows the proliferation of Pityrosporum ovale or Pityrosporum orbiculare (Malassezia furfur), (17) which can cause a brown, pink, or reddish discoloration of the skin.

Technically a papulosquamous eruption, tinea versicolor presents as numerous macules or slightly raised papules with subtle scale. Patients may have a coalescence of lesions or a single patch with an irregular border. The lesions of tinea versicolor may be several centimeters in diameter, or they may cover most of the trunk.

Over time, the Pityrosporum species can block the conversion of tyrosine to melanin, (18) leading to hypopigmented patches instead of increased coloration. The scale on the surface of the affected skin (Figure 8) and the "spaghetti and meatball" appearance of fungal forms on a potassium hydroxide preparation help to clarify the diagnosis.