eMedicine Specialties > Dermatology > Benign Neoplasms

Seborrheic Keratosis

Author: Arthur K Balin, MD, PhD, FACP, Clinical Professor, Lankanau Medical Research Center, Jefferson Health System
Contributor Information and Disclosures

Updated: Jan 6, 2009

Introduction

Background

Seborrheic keratoses are the most common benign tumor in older individuals. Seborrheic keratoses have a variety of clinical appearances, and they develop from the proliferation of epidermal cells. Although no specific etiologic factors have been identified, they occur more frequently in sunlight-exposed areas.

Pathophysiology

Reticulated seborrheic keratoses are usually found on sun-exposed skin, and the reticulated type of seborrheic keratoses may develop from solar lentigines.

Epidermal growth factors or their receptors have been implicated in the development of seborrheic keratoses.^1,2,3 No difference was observed in the expression of immunoreactive growth hormone receptors in keratinocytes from normal epidermis and keratinocytes from seborrheic keratoses. The expression of BCL2, an apoptosis-suppressing oncogene, is low in seborrheic keratosis in contrast to the high values in basal cell and squamous cell carcinoma.⁴ No increase is observed in the sonic hedgehog signal transducers patched (ptc) and smoothened (smo) messenger RNA (mRNA) in seborrheic keratosis over normal skin.⁵

A high frequency of mutations in the gene encoding the tyrosine kinase receptor FGFR3 (fibroblast growth factor receptor 3) has been found in certain types of seborrheic keratoses. This may the first clue into the genetic basis for the pathogenesis of seborrheic keratoses. FGFR3 belongs to a class of transmembrane tyrosine kinase receptors involved in signal transduction to regulate cell growth, differentiation, and migration, as well as wound healing and angiogenesis. Upon ligand binding, FGFR3 dimerizes, which, in turn, induces phosphorylation of the kinase domain. Activating mutations in FGFR3 have been found in approximately 40% of hyperkeratotic seborrheic keratoses, 40% of acanthotic seborrheic keratoses, and 85% of adenoid seborrheic keratoses.^6,7,8

Seborrheic keratoses have a varying degree of pigmentation. In pigmented seborrheic keratoses, the proliferating keratinocytes trigger the activation of neighboring melanocytes by secreting melanocyte-stimulating cytokines. Endothelin-1 has dual stimulatory effects on DNA synthesis and melanization of human melanocytes and has been implicated as playing a part in the hyperpigmentation observed in seborrheic keratoses.⁹ Immunohistochemically, the keratinocytes of seborrheic keratoses express low molecular weight keratin but often exhibit a partial lack of the high molecular weight forms of keratin.

Frequency

United States

Seborrheic keratoses are the most common benign tumor in older individuals. The frequency appears to increase with age. In 1963, Tindall and Smith examined a population of individuals older than 64 years in North Carolina and found that 88% of the people had at least one seborrheic keratosis.¹⁰ In this study, 38% of the white women, 54% of the white men, and 61% of the black men and women were found to have 10 or more seborrheic keratoses. In 1965, Young examined 222 residents of the Orthodox Jewish Home for the Aged in New York and found that 29.3% of the men and 37.9% of the women had seborrheic keratosis.

International

In 2000, Memon et al found in a British population younger than 40 years that 8.3% of the males and 16.7% of the females had at least one seborrheic keratosis.¹¹ In an Australian population, 23.5% of individuals aged 15-30 years were found to have at least one seborrheic keratosis, with no significant differences between the sexes. In another Australian study of 100 people composed of hospital staff and nondermatologic day patients, 12% of people aged 15-25 years (n = 34), 79% of people aged 26-50 years (n = 24), 100% of people aged 51-75 years (n = 25), and 100% of people older than 75 years (n = 17) had seborrheic keratoses. The median number of seborrheic keratoses per person was 6 in the group aged 15-25 years, 5 in the group aged 26-50 years, 23 in the group aged 51-75 years, and 69 in those older than 75 years.

Mortality/Morbidity

Seborrheic keratoses are benign but secondary tumors, and Bowen disease (squamous cell carcinoma in situ) or malignant melanoma may occasionally arise within the lesion. Seborrheic keratoses can also catch on clothing and become irritated. They can itch, grow, and bleed.

• Scratching seborrheic keratoses or trying to pick them off the skin can result in a secondary infection.
• People sometimes have many seborrheic keratoses, and they may obscure the detection of a dysplastic nevus or malignant melanoma.

Race

Seborrheic keratoses are less common in populations with dark skin compared to those having white skin; however, black individuals develop a variant of seborrheic keratoses termed dermatosis papulosa nigra. These lesions affect the face, especially the upper cheeks and lateral orbital areas. They are small, pedunculated, and heavily pigmented with a minimal keratotic element. The onset of these lesions generally is earlier than that of ordinary seborrheic keratoses.

Sex

No sex difference is apparent in the frequency of occurrence of seborrheic keratoses.

Age

Seborrheic keratoses are the most common benign tumor in older individuals. They appear to increase with age. Seborrheic keratoses have also been found to occur in younger individuals.

Clinical

History

• Seborrheic keratoses usually are asymptomatic, but they can be an annoyance. Lesions can itch and rub or catch on clothing, thereby becoming inflamed.
• Lesions often are unattractive and serve as negative psychological connotations—daily reminders of aging.
• Patients are sometimes concerned that these enlarging lesions are malignant.
  • Sometimes a person may have many seborrheic keratoses and not notice a dysplastic nevus or a malignant melanoma that develops among the seborrheic keratoses.
  • A significant danger can arise if a person does not detect a malignant melanoma at an early stage.
• Although lesions may resolve on occasion, spontaneous resolution does not ordinarily occur.
• The sign of Lesser-Trélat is the association of multiple eruptive seborrheic keratoses with internal malignancy. Most commonly, the sign is observed with adenocarcinoma, especially of the gastrointestinal tract; however, an eruption of seborrheic keratoses may develop after an inflammatory dermatosis (eg, eczema,¹² severe sunburn).
• Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous.
• As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance.
• They typically have an appearance of being stuck on the skin surface.
• The color of the lesions can vary from pale brown with pink tones to dark brown or black.
• Their natural history includes slow enlargement with increasing thickness and the gradual development of new lesions.
• A familial trait exists for the development of multiple seborrheic keratoses in about half of the patients, with an autosomal dominant mode of inheritance.
• Seborrheic keratoses can occur on almost any site of the body, with the exception of the palms and soles and mucous membranes.
  • In an Australian study of the site of distribution of 3067 seborrheic keratoses, 54.7% were found on the trunk, 15.2% on the hands, 11.4% on the face and neck, 8.5% on the arms, 2.6% on the upper leg, 6% on the lower leg, and 1.6% on the feet.
  • In this study, seborrheic keratoses were found to be most concentrated on the head and neck and hands, areas with the highest amount of sun exposure.¹³

Physical

Initially one or more sharply defined, light brown, flat lesions develop with a velvety to finely verrucous surface. They arise on normal skin. Their initial size is usually less than 1 cm, but the lesions can grow to several centimeters or more. With time, the lesions become thicker and have an appearance of being stuck on the skin surface.

• Fully developed seborrheic keratoses often are deeply pigmented and do not reflect light.
• Many lesions show keratotic plugging of the surface.
• Some lesions are covered by an adherent greasy-appearing scale and are raised above the surface of the skin. Seborrheic keratoses can feel soft and greasy.
• The shape is round to oval, and multiple lesions may be aligned in the direction of skin folds.
• The smallest lesions are placed around follicular orifices, especially on the trunk.
• Most seborrheic keratoses have fewer hairs than the surrounding skin that they come from.
• Sometimes the lesions can grow large, with individual seborrheic keratoses reaching up to 35 X 15 cm.
• Epiluminescent surface microscopic examination of seborrheic keratoses reveals globulelike structures. The globule like structures in seborrheic keratoses are due to intraepidermal horn cysts filled with cornified cells containing melanin. They resemble the brown globules observed in melanocytic neoplasms, which are due to nests of melanocytes at the dermoepidermal junction.
• Irritation can cause swelling and sometimes bleeding, oozing, and crusting and a deepening of the color due to inflammation.
• Seborrheic keratoses may become red-brown in color when they become inflamed.
• Variants include the following:
  • Dermatosis papulosa nigra: These lesions affect the face, especially the upper cheeks and lateral orbital areas. They are small, pedunculated, and heavily pigmented with a minimal keratotic element. The onset of these lesions generally is earlier than that of ordinary seborrheic keratoses. These lesions appear to be caused by a nevoid developmental defect of the pilosebaceous follicles. Histologically, they show irregular acanthosis and hyperkeratosis.
  • Stucco keratosis: Some adults develop large numbers of superficial gray-to-light brown flat keratotic lesions favoring the dorsa of the feet, the ankles, and the dorsa of the hands and forearms. Some investigators think these stucco keratoses are a variant of seborrheic keratosis. Histologically, horn cysts are not observed and a regular spiky papillomatosis with a loose lamellated hyperkeratosis capping the epidermis is prominent.
  • Melanoacanthoma: 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.
  • Differential diagnosis: The clinical differential diagnosis of seborrheic keratoses includes malignant melanoma, melanocytic nevus, verruca vulgaris, condyloma acuminatum, fibroepithelial polyp, epidermal nevus, actinic keratoses, pigmented basal cell carcinomas, and squamous cell carcinomas.
    • Melanoma can clinically resemble seborrheic keratosis. A retrospective review of 9204 consecutive pathology reports from the Massachusetts General Hospital containing a clinical diagnosis of seborrheic keratosis revealed that 61 of these specimens (0.66%) were malignant melanoma. The submitted clinical differential diagnosis was seborrheic keratosis versus melanoma (31 cases, 51%), melanocytic nevus (17 cases, 28%), basal cell carcinoma (7 cases, 12%), squamous proliferation (3 cases, 5%), and no other differential diagnosis (3 cases, 5%).
    • Distinguishing superficial seborrheic keratoses from lentigo maligna and pigmented actinic keratoses may be difficult. The pigmented domed variety of acanthotic seborrheic keratoses may closely resemble a melanocytic nevus, but the surface is less lustrous and the follicular orifices are plugged.
    • Some seborrheic keratoses have a verrucous architecture that can produce a clinical and histologic appearance similar to an aging viral wart. Routine histopathologic examination may not reliably make this distinction, and special studies to look for evidence of papillomavirus DNA may be needed.
    • An inflamed seborrheic keratosis may be confused with a malignant melanoma or a squamous cell carcinoma.
    • Pigmented basal cell carcinomas usually are rather irregular with a rolled edge, a thin shiny epidermis with telangiectases, and a depressed or ulcerated center.
    • Inflammatory eruptions (eg, psoriasis,¹⁴ pemphigus erythematosus¹⁵ ) have been confused with seborrheic keratoses.
    • The use of topical products to achieve a "sunless tan" is increasing. Approximately 15% of women aged 18-24 years use sunless tanners. These topical products contain the active ingredient dihydroxyacetone (DHA). The artificial tan can alter the appearance of a skin lesion. More than one patient has been referred to a skin cancer clinic with a history of a change in the appearance of a pigmented lesion from which the use of sunless tanners was revealed after inquiry.¹⁶
  • Polypoid lesions: A clinical variant of the typical seborrheic keratosis is small polypoid lesions around the neck, under the breast, or in the axillae. They are commonly called skin tags, but different from smooth skin tags, these lesions have a furrowed rough surface. They have a predilection for points of chronic trauma.

Causes

The cause of seborrheic keratoses is not known (see Pathophysiology). Some cases are inherited through an autosomal dominant mode of inheritance. Sunlight seems to play a role in the development of some seborrheic keratoses.¹⁷ Evidence indicates that at least some seborrheic keratoses have a clonal nature. Activating mutations in the gene encoding the tyrosine kinase receptor FGFR3 have been found in 85% of adenoid seborrheic keratoses. This is discussed in Pathophysiology.

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