Laboratory Studies
No laboratory tests are needed unless the sudden appearance of multiple pruritic seborrheic keratoses occurs, which is known as the Leser-Trélat sign. This has been associated with the development of adenocarcinoma of the gastrointestinal tract, [27] lymphoma, Sézary syndrome, and acute leukemia.
Imaging Studies
No imaging studies are needed, unless the sudden appearance of multiple pruritic seborrheic keratoses occurs (known as the Leser-Trélat sign).
Procedures
The shave biopsy provides histologic material for accurate diagnosis and removes the lesion in a cosmetically acceptable manner at the same time. After a shave biopsy is obtained, a curette can be used to smooth and remove any remaining keratotic material.
Histologic Findings
These lesions are raised above the skin surface, and they show a papillomatous epithelial proliferation containing horn cysts without any tendency toward malignancy. The proliferating cells are epidermal and have a basaloid appearance. The number of epidermal basal cells is greatly increased. The acanthotic pattern (see the images below) is the most frequent, in which a thick layer of basal cells is observed interspersed with pseudo-horny cysts. Invaginations to form keratin-filled pseudocysts are present. Some of these cells contain melanin.
Hyperkeratotic seborrheic keratoses, shown in the images below, have pronounced hyperkeratosis and papillomatosis with less acanthosis. When papillomatosis is particularly prominent, the histology resembles acrokeratosis verruciformis of Hopf. The epidermis is largely composed of squamous cells interspersed with aggregates of basaloid cells.

The reticulated or adenoid type (shown in the images below) of seborrheic keratoses contains numerous thin tracts of basaloid epidermal cells that are branched and interwoven. They have less epidermal thickening, and horn pseudocysts usually are less prominent in reticulated seborrheic keratoses. Marked hyperpigmentation is often present, and they have some histologic similarity to lentigo senilis.
An acantholytic type with acantholysis also occurs and is particularly prominent in the squamous eddies of irritated seborrheic keratosis. Irritated seborrheic keratoses show a change from the basaloid keratinocytes observed in the acanthotic type, which are more mature squamous cells, to cells that are sometimes associated with mild nuclear atypia. The keratinocytes are arranged in swirls or whorls known as squamous eddies. Spindling of keratinocytes is common. Inflammatory cells are often observed intermingled with the proliferated epidermal cells, shown in the image below.

The clonal seborrheic keratoses show well-demarcated nests of basaloid or larger squamous cells within an acanthotic seborrheic keratoses. Melanoacanthoma is a deeply pigmented seborrheic keratosis in which an acanthotic proliferation of large dendritic melanocytes is identified. It probably represents a concomitant proliferation or activation of the dendritic melanocytes and epidermal cells. Lichenoid seborrheic keratosis is an inflammatory variant. In one study of 108 seborrheic keratoses, 66% were acanthotic, 25% were hyperkeratotic, and 9% had a reticulated (adenoid) pattern. In this study, 5.5% (6/108) of the specimens contained squamous cell carcinoma and 4 of these appeared to develop within the central portion of the lesion. Also, 4 of the 6 malignancies developed in the reticulated type of seborrheic keratoses.
In irritated seborrheic keratoses, pronounced squamous metaplasia can occur, which may be misdiagnosed as basosquamous carcinoma. This phenomenon is not due to human papillomavirus. [28] Human papillomavirus can be identified in the seborrheic keratoses of patients with epidermodysplasia verruciformis and in seborrheic keratosis–like lesions exhibiting bowenoid changes. These probably should be considered as condylomata rather than as true seborrheic keratoses. [29, 30]
The histologic differential diagnosis of seborrheic keratoses includes verruca vulgaris, fibroepithelial polyp, condyloma acuminatum, acanthosis nigricans, epidermal nevus, confluent and reticulated papillomatosis of Gougerot and Carteaud, hidroacanthoma simplex, [31] acrokeratosis verruciformis of Hopf, lentigo senilis, and tumor of the follicular infundibulum.
Acanthotic seborrheic keratoses may be confused with eccrine poromas, but no ductular differentiation is observed in seborrheic keratosis. Hidroacanthoma simplex can be distinguished from clonal seborrheic keratosis by the presence of ductal and cystic spaces histologically and by a lower density of Langerhans cells and fewer melanin granules in the intraepidermal nests. Verruca vulgaris can usually be differentiated from seborrheic keratoses because verruca vulgaris usually displays keratohyalin granule clumping, perinuclear vacuolization, and ectatic vessels within the papillary dermal tips.
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Sharply circumscribed elevated seborrheic keratoses.
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Closer view of multiple seborrheic keratoses in an autosomally dominant mode of inheritance.
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Seborrheic keratoses projecting above the level of the epidermis. Cysts represent sections of hyperkeratotic follicles.
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Seborrheic keratosis showing lackluster surface and appearance of being stuck on the skin surface.
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This is an autosomal dominant form of multiple seborrheic keratoses. This man's daughter is developing a similar distribution and quantity of seborrheic keratoses.
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The back of this same patient as in the image above with multiple seborrheic keratoses. His face had a similar number of seborrheic keratoses.
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Acanthotic type of seborrheic keratosis.
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Higher-power view of the cells in an acanthotic seborrheic keratosis.
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Hyperkeratotic type of seborrheic keratosis.
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Reticulated (or adenoid) type of seborrheic keratosis.
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This is a reticulated (or adenoid) seborrheic keratosis with abundant pigment.
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Seborrheic keratosis with inflammation in the dermis.
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This seborrheic keratosis was a pedunculated lesion in an axillary fold. Clinically, it had some resemblance to a skin tag.