Seborrheic Keratosis



Seborrheic Keratosis







Key Points



  • Seborrheic keratosis (SK) is the most common benign epithelial tumor and accounts for about 20% of benign epithelial neoplasms seen on the eyelid


  • The pathogenesis of SK is not completely understood, but they are considered to arise in aging skin associated with UV exposure


  • It does not represent reactive epidermal hyperplasia but more likely results from clonal expansion of a somatically mutated keratinocyte


  • Genetic mutations have been detected in SK, showing a typical UV signature


  • They present as sharply demarcated, skin-colored to darkly pigmented hyperkeratotic, slightly elevated lesions with a “stuck-on” appearance, occasionally associated with a cutaneous horn


  • Treatment is generally not required, but when removal is desired for cosmetic reasons, surgical shave excision, electrodesiccation, or curettage are frequently used options


  • The prognosis for seborrheic keratosis is generally very good


Seborrheic keratosis (SK) is the most common benign epithelial tumor.1 It is estimated that about 83 million people in the United States are affected with SK, primarily middle-aged and elderly adults.2 Lesions are seen most often on the eyelids and face, but also can be seen on the chest, back, and abdomen.3 SK accounts for about 20% of benign epithelial neoplasms seen on the eyelid.4,5 The occurrence of SK on the conjunctiva is very rare, with only a few cases reported.6,7,8,9 They may be pigmented or nonpigmented, and when pigmented, they can be misdiagnosed as melanoma.

Rare cases of familial SK have been reported, including lesions presenting at a younger age. These cases tend to support a hereditary background, and somatic activating mutations of FGFR3 have been identified in some lesions.10,11 These mutations may be early events in the pathogenesis of a subset of SK, conferring a risk factor independent of age or ultraviolet (UV) radiation exposure.12 However, the underlying genetic alterations in familial SK are still not clearly understood.

Dermatosis papulosa nigra has been described as a clinical variant of SK with multiple tiny lesions. It is more common in patients of African and Asian descent, and females are affected twice as often as males. Positive family history is seen in up to 85% of cases.13 Although some authors consider this a distinct entity, the histopathology is identical to that of SK.14,15

The Leser-Trélat sign is the sudden appearance of multiple eruptive SKs as a paraneoplastic disorder associated with an underlying malignancy such as lung, esophageal, and nasopharyngeal carcinoma, mycosis fungoides, Sézary syndrome, and plasmacytoma.16,17,18,19,20,21 Because of this relationship, screening for systemic cancer is recommended in cases of abrupt development of multiple pruritic SKs.


Etiology and Pathogenesis

The pathogenesis of SK is not completely understood, but they are considered to arise in aging skin associated with UV exposure. Studies have shown that some benign lesions, including SK, accumulate a number of UV-induced genomic aberrations.22,23 SK does not represent reactive epidermal hyperplasia but more likely results from clonal expansion of a somatically mutated keratinocyte.24 Even though SK does not have a malignant potential, more than 80% have at least one mutation, and 45% have more than one oncogenic mutation.25

A viral etiology involving human papillomavirus has been proposed, but this has not been substantiated in recent studies.26,27 Amyloid precursor protein (APP) and its downstream products are expressed more strongly in SK than in adjacent normal skin tissues, and also more strongly in UV-exposed skin compared with nonexposed skin. This suggests that overexpression of APP may promote the initiation of SK in aging, UV-damaged skin.28

Genetic mutations have been detected in SK, showing a typical UV signature. FGFR3 mutations are the most frequent, detected in 48% of SK lesions, followed by the PIK3CA (32%), TERT promoter (24%), and DPH3 promoter mutations (24%).29 Neel et al30 reported oncogenic mutations in the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt signaling cascade and demonstrated that SK are sensitive to Akt inhibition. SK and squamous cell carcinoma (SCC) are both clonal tumors derived from keratinocytes, and they both have similar and overlapping genomic alterations.31 Yet SK exhibits a benign clinical behavior and remains in situ, whereas cutaneous SCC
is locally invasive and has a small but definite malignant potential. SK is not a precursor lesion to SCC.30 In SK there is a defect in the cornification process of epithelial differentiation, where some cells live longer than normal and undergo inappropriate intraepithelial cornification, forming so-called pseudocysts.30 The high levels of Akt activity seem to underlie this pathological condition.


Clinical Presentation

Clinically, SKs typically present as sharply demarcated, hyperkeratotic, slightly elevated lesions with a “stuck-on” appearance (Figures 115.1 and 115.2)32 and occasionally can be associated with a cutaneous horn.32,33 They vary from skin-colored to darkly pigmented, and from a flat macule to an elevated nodule, and can be associated with irritation or inflammation. Irritative symptoms are frequent and lesions can become ulcerated, mimicking malignant cutaneous tumors such as basal cell carcinoma and SCC.7,34,35 Although most SKs are 4 cm or less in diameter, giant lesions occasionally develop.36






A number of dermoscopic features have been shown to characterize SK.37,38,39 These include comedo-like openings, milia-like cysts, fissures, ridges, hairpin vessels, and multiple horn pearls.38,40 Fissures and ridges, sometimes referred to as gyri and sulci, are thick, curved, sometimes branched lines varying from hypopigmented to brown, black, or blue that correlate with the papillomatous surface of the epidermis. Hairpin or looped vessels are two parallel vessels that form a half-looped or hairpin-like structure. They are often surrounded by a white halo and are often multiple and monomorphous in SK lesions. But they are not specific to SK and can also be observed in melanoma, SCC, basal cell carcinoma, and
other cutaneous neoplasms. Histologically, hairpin vessels correspond to enlarged capillaries of the dermal papillae.37 Dark brown, gray, or black, round to oval clefts containing keratin plugs, called comedo-like openings, correspond to pseudohorn cysts in the epidermis that open to the surface of the lesion. Milia-like cysts are round, well-circumscribed, white to yellowish structures that correspond to intraepidermal cysts, and multiple such cysts are characteristic of SK.


Differential Diagnosis

The differential diagnosis of SK includes melanocytic nevus, verruca vulgaris, actinic keratosis, acanthosis nigricans, pigmented basal cell carcinoma, and malignant melanoma.41