Seborrheic keratosis

INTRODUCTION — Seborrheic keratosis (SK) is a common benign skin neoplasm consisting of immature epidermal keratinocytes [1,2]. It presents with various morphologies, ranging from a lightly pigmented, superficial patch to a brown to black, scaly papule or plaque with a "stuck-on" appearance. SKs are primarily seen in adults and older adults.

The clinical features, diagnosis, differential diagnosis, and management of SK are discussed here. Dermatofibroma and an overview of other benign skin lesions are presented separately.

●(See "Dermatofibroma (benign fibrous histiocytoma)".)

●(See "Overview of benign lesions of the skin".)

EPIDEMIOLOGY — SK is one of the most common, if not the most common, benign skin tumors occurring in adults and older individuals of all ethnicities without sex predilection. Its prevalence increases with age, reaching nearly 100 percent in individuals older than 60 years [3-7].

PATHOGENESIS — The pathogenesis of SK is poorly understood. Evidence for a role of cumulative ultraviolet (UV) radiation exposure [8,9] or human papillomavirus (HPV) infection [10,11] is inconsistent. Somatic activating variants in the fibroblast growth factor receptor 3 (FGFR3) and PIK3CA oncogenes and, with lower frequency, in TERT and DHPH3 promoters have been found in SKs [12,13]. However, their significance in the development of SK remains unclear [14].

CLINICAL FEATURES

General features

●Morphology – SKs present with a spectrum of clinical morphologies, although most fit into the classic description of stuck-on, hyperkeratotic or scaly, adherent papules ranging in color from light tan to brown or black (picture 1A-D). The surface is typically dull and has numerous plugged follicular orifices that result in a cerebriform appearance (picture 2).

Early lesions appear as flat, light brown or skin-colored, macular lesions resembling lentigines (picture 3A-B).

●Location and distribution – SKs can appear on any nonglabrous surface of the body. The number can vary from an isolated lesion to literally hundreds. Frequently, SKs cluster on the trunk, in the inframammary folds, on the face/scalp, and on the arms and legs. In skin folds, SK may be pedunculated. A "Christmas tree" pattern may be seen on the back due to lesion distribution along the Blaschko lines (picture 4).

●Symptoms – SKs are usually asymptomatic. However, inflamed or irritated lesions (picture 5), especially those located in skin folds or subject to persistent irritation from friction with clothing, may be associated with pruritus and/or mild pain.

Clinical variants — Specific clinical variants of SK include:

●Stucco keratosis – Some patients may present with an array of small, white, fine, stuck-on SK papules, typically located on the ankles and dorsum of the feet, called "stucco keratoses" (picture 6).

●Dermatosis papulose nigra – Patients with darkly pigmented skin may develop an acanthotic variant of SK called dermatosis papulosa nigra. It presents with brown to black papules, predominantly located on the face and neck (picture 7A-D), that increase in number with age.

Sign of Leser-Trélat — The sign of Leser-Trélat, which refers to the sudden appearance of multiple SKs in association with skin tags and acanthosis nigricans, has been associated with a variety of malignancies, including gastrointestinal and lung cancers. (See "Cutaneous manifestations of internal malignancy", section on 'Sign of Leser-Trélat'.)

NATURAL HISTORY — Most patients notice their first SK in mid-adulthood. They grow slowly in size and number over the years.

DIAGNOSIS

Clinical — The diagnosis of SK is usually a clinical one, based on its distinctive appearance as a stuck-on, scaly, brown to black, adherent papule (picture 1A-D) that is easily recognized by the experienced clinician.

Dermoscopy — Dermoscopy can support the clinical diagnosis of SK. Typical dermoscopic findings of SK include comedo-like openings, milia-like cysts, gyri and sulci, and hairpin vessels (picture 8A-C). Although some typical dermoscopic features may be obscured in heavily pigmented SKs, features of melanocytic lesions, such as pigment network or globules, are absent. (See "Dermoscopic evaluation of skin lesions", section on 'Seborrheic keratoses and solar lentigo'.)

Biopsy and histopathology

●When to biopsy – A lesion biopsy is generally not needed for the diagnosis of SK. However, if the clinical or dermoscopic diagnosis are unclear, biopsy and histopathologic examination should be performed to exclude melanoma, squamous cell carcinoma, or basal cell carcinoma. (See 'Differential diagnosis' below.)

●Typical histopathologic features – On histopathology, SKs are typically described as well-demarcated intraepidermal proliferations of typical but immature keratinocytes, frequently with papillomatosis, acanthosis, hyperkeratosis, and horn cysts. Melanocytes and melanin may be present in various amounts depending on lesion pigmentation.

●Histologic subtypes – Several histologic subtypes have been identified, including the acanthotic/solid type (most common), the hyperkeratotic type, the reticular/adenoid type (frequently seen in facial SKs), and the clonal type. Clonal SK is characterized by two distinct clones of basaloid cells. One of them appears as nests of cytologically distinct keratinocytes that expand the stratum spinosum between normal acanthotic epidermis [15]. Cytologic atypia has been reported in approximately 50 percent of clonal SKs, with rare progression to cutaneous squamous cell carcinoma in situ [15].

DIFFERENTIAL DIAGNOSIS — Several benign and malignant skin lesions can mimic SKs [16].

●Viral warts – Hyperkeratotic SKs may have considerable clinical and histologic overlap with common warts (verruca vulgaris). In the author's experience, lesions with an SK appearance in the genital/perineal area may frequently represent genital warts (condyloma acuminata), and as such, biopsies and human papillomavirus (HPV) typing may be a consideration versus empiric treatment with destructive methods. (See "Cutaneous warts (common, plantar, and flat warts)".)

●Actinic keratosis and keratinocyte carcinoma – On the face and sun-exposed areas, pigmented SKs may be confused with pigmented actinic keratosis, cutaneous squamous cell carcinoma, or pigmented basal cell carcinoma (picture 9). However, these lesions lack the typical stuck-on appearance of SK. (See "Actinic keratosis: Epidemiology, clinical features, and diagnosis".)

●Melanoma – Melanomas with features mimicking SKs as well as collision tumors are exceedingly rare but have been reported [17-19]. The clinical and dermoscopic diagnosis of melanoma mimicking SK is challenging. Notably, hyperkeratosis is not generally associated with melanoma, and most melanomas are superficial spreading type and macular (flat) in appearance, whereas most SKs are raised, hyperkeratotic lesions. On dermoscopy, the presence of blue-white veil, pseudopods or streaks, and pigment network suggests melanoma [16,18]. A biopsy and histologic examination are essential for the correct diagnosis of lesions showing ambiguous clinical and dermoscopic features. (See "Melanoma: Clinical features and diagnosis".)

MANAGEMENT — SKs are benign and slow-growing lesions and generally do not require treatment. However, patients may require treatment for lesions that are symptomatic, cause functional impairment (eg, affect vision), or that cause cosmetic concerns.

Treatments commonly used in clinical practice include a variety of destructive measures, most commonly liquid nitrogen cryotherapy, electrocautery, curettage, shave removals, or snip removal in the case of pedunculated lesions [2]. The choice of treatment is based on the size and location of the lesion and on patient preference.

●Locally destructive treatments

•For removal of superficial SKs, we suggest liquid nitrogen cryotherapy as first-line treatment. Liquid nitrogen cryotherapy is easily available, rapid, and does not require local anesthesia. Following treatment, blistering and crusting are expected to occur in the treated areas, which typically heal in one to three weeks. Recurrence may occur. Long-term adverse effects include hypo- or hyperpigmentation and scarring. (See "Minor dermatologic procedures", section on 'Cryotherapy (cryosurgery)'.)

•Electrodesiccation and curettage (ED&C) is an alternative treatment, particularly for large, thick SKs. ED&C requires local anesthesia and carries a higher risk of scarring compared with cryotherapy. (See "Minor dermatologic procedures", section on 'Curettage and electrodesiccation'.)

•Ablative laser treatment with erbium-doped yttrium aluminum garnet (Er:YAG) or carbon dioxide (CO₂) lasers is an additional option. Potential adverse effects of laser treatment include hypo- or hyperpigmentation and scarring. Cost may be a limitation. (See "Principles of laser and intense pulsed light for cutaneous lesions".)

•Shave biopsy or curettage are indicated for lesions that are not unequivocally diagnosed as SK clinically and/or dermoscopically and require histopathologic examination. (See "Skin biopsy techniques".)

Evidence for the efficacy of destructive treatments for SK is limited to a few small studies.

•A small intrapatient comparative study that included 25 adults examined the efficacy and patient satisfaction for cryotherapy or simple curettage for the treatment of SK [20]. At six weeks, the mean patient ratings for cosmetic outcome were similar for both procedures, though 15 of 25 patients (60 percent) preferred cryotherapy.

•In another study that included 33 patients, two similar SKs on the trunk of each patient were randomly assigned to cryosurgery or electrodesiccation [21]. At eight weeks, 25 lesions (81 percent) in both intervention groups were considered completely cleared by a clinician blinded to lesion assignment. Patient preference was similar for the two procedures at baseline and at two and eight weeks. However, at eight weeks, lesions treated with electrodesiccation were more likely to have residual hyperpigmentation compared with lesions treated with cryotherapy.

•In an intrapatient comparative study that included 42 patients with multiple SKs on the face, neck, and trunk treated with Er:YAG laser or cryotherapy, laser treatment was associated with more rapid healing and less hyperpigmentation compared with cryotherapy [22].

●Topical agents – Several topical agents, including hydrogen peroxide 40% solution [23], tazarotene 0.1% ointment [24], 50% trichloroacetic acid [25], and calcipotriol 0.005% ointment [26], have been evaluated for the treatment of SK in a few uncontrolled studies. However, their efficacy is limited.

PROGNOSIS — SKs are benign keratinocytic neoplasms without malignant potential. Recurrence of treated lesions and development of new lesions over time may occur.

SUMMARY AND RECOMMENDATIONS

●Definition – Seborrheic keratosis (SK) is a common benign skin neoplasm consisting of immature epidermal keratinocytes. It typically occurs in adults and older individuals, with a prevalence approaching 100 percent in people older than 60 years.

●Clinical presentation – SKs present with a spectrum of clinical morphologies, although most fit into the classic description of stuck-on, hyperkeratotic or scaly, adherent papules ranging in color from skin colored to tan, brown, or black (picture 1A-D). They vary in number from a single or few isolated lesions to hundreds. Patients with darkly pigmented skin may develop a variant of SK called dermatosis papulosa nigra, which presents with brown to black papules predominantly located on the face and neck (picture 7A-D). (See 'Clinical features' above.)

●Diagnosis – The diagnosis of SK is usually a clinical one, based on its distinctive appearance. Dermoscopy can support the clinical diagnosis. Typical dermoscopic findings of SK include comedo-like openings, milia-like cysts, gyri and sulci, and hairpin vessels (picture 8A-C). Biopsy and histopathologic examination should be performed if the clinical diagnosis is uncertain. (See 'Diagnosis' above.)

●Management – SKs are benign and slow-growing lesions and generally do not require treatment. However, patients may desire treatment for lesions that are symptomatic (eg, chronically irritated, itchy) or cause cosmetic concerns. For removal of superficial SKs, we suggest liquid nitrogen cryotherapy as first-line treatment rather than other destructive treatments, such as electrodesiccation and curettage (ED&C) or laser ablation (Grade 2C). Liquid nitrogen cryotherapy is easily available, rapid, and does not require local anesthesia.

ED&C is an alternative treatment, particularly for large, thick SKs. ED&C requires local anesthesia and carries a higher risk of scarring compared with cryotherapy. Laser ablation is an additional treatment modality, but cost may be a limitation. (See 'Management' above.)