Seborrheic Keratosis

Seborrheic keratosis (SK) is the most common benign epithelial cutaneous neoplasm. The condition consists of immature keratinocytes. Seborrheic keratosis is the most common benign skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin tumor in middle-aged and elderly adults and presents as a sharply demarcated, exophytic, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesion that may be tan or black and has a “stuck-on” appearance. Pruritus or pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain can occur if these lesions become secondarily inflamed by trauma, especially if they are within the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin folds. Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics are thought to play a role, but the pathogenesis is uncertain. The most common mutations involve two oncogenes: fibroblast growth factor receptor 3 (FGFR3) and PIK3CA. There is a familial predisposition to develop a high number of seborrheic keratoses. Treatment is not necessary, as this is a benign condition, but cryotherapy, curettage or electrodesiccation can be performed for discomfort or cosmetic concerns.

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Overview

Definition

Seborrheic keratosis (SK) is a benign skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin tumor consisting of proliferating immature keratinocytes.

Epidemiology

  • Seborrheic keratoses are the most common benign tumors in middle-aged and older adults.
  • Most adults will develop at least 1 SK in their lifetime.
  • Age group prevalence: 
    • 15–25 years: 8%–24% have at least 1 SK
    • > 64 years: 90% have at least 1 SK; 30%–60% have ≥ 10 SKs
  • More frequent in people with lighter skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin tones
  • Sex: No differences

Etiology

  • Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics:
    • Most common mutations in two oncogenes: fibroblast growth factor receptor 3 (FGFR3) and PIK3CA
    • Familial/genetic predisposition to develop a high number of seborrheic keratoses
  • Leser–Trélat sign: 
    • Paraneoplastic syndrome associated with sudden eruption of multiple SKs caused by an internal malignancy
    • Possibly due to hypersensitivity to a growth factor (GF) from the tumor (e.g., epidermal GF or alpha-transforming GF)
  • Cumulative UV radiation exposure:
    • Most mutational patterns are typical UV signature types with C > T and CC > TT base changes at dipyrimidinic sites.
    • More common in lighter-skinned people; 3× more common in Australian surfers
  • HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomaviridae: HPV infection: inconsistent evidence

Pathophysiology and Clinical Presentation

Pathogenesis

  • Clonal expansion of somatically mutated cells (not epidermal hyperplasia):
    • Growth is driven by mutations in oncogenes, most commonly FGFR3 and PIK3CA.
    • Genetically stable (unlike malignant tumors)
  • Lack malignant potential, possibly owing to:
    • Lack of tumor suppressor gene mutations
    • FGFR3 stimulation of the differentiation transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factor FOXN1

Morphology

  • Sites: hair-bearing surfaces only (e.g., trunk, head, neck, face, extremities, genitals)
  • Size: 0.2 cm to > 3 cm
  • Shape: domed or flat-topped; round or irregular borders
  • 3 characteristics common to all SKs:
    • Sharply circumscribed borders (can be irregular)
    • “Stuck-on” appearance due to growth being limited to epidermis
    • Tan, brown, or black color (can be variegated)
  • Surface characteristics are uniform in each lesion (differentiate from melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma):
    • Rough-surfaced SKs more common than smooth-surfaced: submillimeter keratinous horn pearls on surface (differentiate from melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma)
    • Waxy appearance due to keratin production
  • Solitary or multiple lesions: increasing number with age

Histology

  • Exophytic proliferative lesion, composed of small keratinocytes entirely within epidermis, without cytologic atypia; similar to basal cells of normal epidermis
  • “Horn pseudocysts”: round intralesional cysts of loose keratin
  • Lesion extends uniformly at one depth only such that a horizontal line can be drawn parallel to the epidermal surface underlying the lesion (“string sign”).
  • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables melanin pigmentation is present.
  • Many histologic variants but no clinical significance (e.g., hyperkeratotic, irritated with pronounced squamous metaplasia)

Clinical presentation

  • Raised skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions with stuck-on appearance
  • Well-demarcated, with verrucous surface
  • Tan, brown, or black
  • Single or multiple
  • Usually painless, but friction trauma may cause bleeding and pruritus.
Seborrheic keratosis with rough surface

Seborrheic keratosis with rough surface:
Note the typical waxy appearance, the well-circumscribed border, and the superficial stuck-on appearance.

Image: “Queratose seborreica 2” by Lmbuga. License: Public Domain
Multiple eruptive seborrheic keratoses

A and B: Leser–Trélat sign in a 92-year-old woman with advanced ovarian cancer Ovarian cancer Ovarian cancer is a malignant tumor arising from the ovarian tissue and is classified according to the type of tissue from which it originates. The 3 major types of ovarian cancer are epithelial ovarian carcinomas (EOCs), ovarian germ cell tumors (OGCTs), and sex cord-stromal tumors (SCSTs). Ovarian Cancer. Multiple eruptive seborrheic keratoses had dramatically increased in size and number over the previous 2 years.
C: CT scan showing a necrotic ovarian tumor accompanied by signs of peritoneal carcinomatosis

Image: “Leser-Trélat sign presenting in a patient with ovarian cancer Ovarian cancer Ovarian cancer is a malignant tumor arising from the ovarian tissue and is classified according to the type of tissue from which it originates. The 3 major types of ovarian cancer are epithelial ovarian carcinomas (EOCs), ovarian germ cell tumors (OGCTs), and sex cord-stromal tumors (SCSTs). Ovarian Cancer: a case report” by Bölke E, et al. License: CC BY 3.0

Diagnosis and Management

Diagnosis

Physical exam:

  • Classic clinical appearance
  • Typically on trunk, face, or upper extremities
  • Horn cysts can be seen with hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand lens.

Dermoscopy:

  • Milia cysts, comedo-like openings
  • Cerebriform pattern (ridges and fissures)

Biopsy:

  • If diagnosis is uncertain and malignancy is suspected
  • Rarely may coexist with melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma or basal cell carcinoma Basal cell carcinoma Basal cell carcinoma is the most common skin malignancy. This cancer arises from the basal layer of the epidermis. The lesions most commonly appear on the face as pearly nodules, often with telangiectatic blood vessels and ulceration in elderly individuals. Basal Cell Carcinoma

Management

  • Treatment is generally not required.
  • If lesion is symptomatic or causes cosmetic problems, various removal methods can be used, depending on size of lesion and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin type:
    • Cryotherapy: 
      • Most common method, particularly for flat or thin lesions
      • Minimal postoperative wound care needed
      • Avoid in dark-skinned individuals (may cause hypopigmentation)
    • Curettage/shave excision: can submit to pathology for diagnosis
    • Electrodesiccation: alone or followed by curettage
    • Lasers: many types
    • 40% hydrogen peroxide: modest efficacy only

Differential Diagnosis

  • Melanoma: most lethal malignant skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin tumor, derived from the malignant transformation of melanocytes: Melanomas present as growing pigmented skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions, raised or flat, usually with irregular borders and color variegation. Diagnosis is established with biopsy. Melanomas are treated with wide local excision.
  • Actinic keratosis Actinic keratosis Actinic keratosis (AK) is a precancerous skin lesion that affects sun-exposed areas. The condition presents as small, non-tender macules/papules with a characteristic sandpaper-like texture that can become erythematous scaly plaques. Actinic Keratosis (AK): Actinic keratoses are precancerous lesions that affect sun-exposed areas and consist of atypical/dysplastic keratinocytes that do not occupy the complete thickness of the epidermis. These lesions may spontaneously resolve, remain stable, or progress to squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma or sometimes basal cell carcinoma Basal cell carcinoma Basal cell carcinoma is the most common skin malignancy. This cancer arises from the basal layer of the epidermis. The lesions most commonly appear on the face as pearly nodules, often with telangiectatic blood vessels and ulceration in elderly individuals. Basal Cell Carcinoma. Diagnosis can be established on the basis of the clinical appearance and biopsy. Actinic keratoses can be managed with excision.
  • Basal cell carcinoma: most common invasive skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin cancer, arising from the basal keratinocytes of the epidermis: Basal cell carcinoma usually presents as raised pearly lesions, most commonly on the face. Diagnosis can be made on the basis of clinical appearance and supported with biopsy. Management is with surgical excision.
  • Squamous cell carcinoma: second most common skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin cancer: Squamous cell carcinoma usually presents as a firm, erythematous, keratotic plaque or papule. Diagnosis is established with biopsy. Treatment is usually surgical excision, but can involve radiation or topical chemotherapy.
  • Atypical nevus Nevus Nevi (singular nevus), also known as "moles," are benign neoplasms of the skin. Nevus is a non-specific medical term because it encompasses both congenital and acquired lesions, hyper- and hypopigmented lesions, and raised or flat lesions. Nevus/Nevi (AN, dysplastic nevus Nevus Nevi (singular nevus), also known as "moles," are benign neoplasms of the skin. Nevus is a non-specific medical term because it encompasses both congenital and acquired lesions, hyper- and hypopigmented lesions, and raised or flat lesions. Nevus/Nevi): Atypical nevus Nevus Nevi (singular nevus), also known as "moles," are benign neoplasms of the skin. Nevus is a non-specific medical term because it encompasses both congenital and acquired lesions, hyper- and hypopigmented lesions, and raised or flat lesions. Nevus/Nevi is a benign lesion but is a phenotypic marker for an increased risk of melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma, especially if there are multiple lesions and/or if there is a positive family history of melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma. An AN may develop into melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma. Diagnosis is made with biopsy. Excision may be required if diagnosis is in doubt.
  • Dermatofibroma (DF): a common, benign, fibrohistiocytic proliferative reaction, usually to trauma, a viral infection, or an insect bite: Dermatofibroma is often present on anterior surfaces of lower legs as a firm, indurated, mobile 0.5–1 cm nodule that retracts beneath the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin during an attempt to compress and elevate it (“retraction,” or “dimple sign”). Diagnosis is usually clinical, and treatment is typically not required.

References

  1. Balin AK AK Actinic keratosis (AK) is a precancerous skin lesion that affects sun-exposed areas. The condition presents as small, non-tender macules/papules with a characteristic sandpaper-like texture that can become erythematous scaly plaques. Actinic Keratosis (AK). (2020). Seborrheic keratosis: background, pathophysiology, etiology. https://emedicine.medscape.com/article/1059477-overview#a7
  2. Dinulos JGH. (2020). Benign skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin yumors. In Dinulos J. (Ed.). Habif’s Clinical Dermatology, 7th ed. Elsevier, pp. 787–793.
  3. Lazar AJ. (2020). The skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin. In Kumar V, et al. (Eds.), Robbins & Cotran Pathologic Basis of Disease. 10th ed. p. 1142.
  4. Goldstein BG, Goldstein AO. (2020). Overview of benign lesions of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin. Uptodate. Retrieved December 24, 2020, from https://www.uptodate.com/contents/overview-of-benign-lesions-of-the-skin
  5. Heidenreich B, et al. (2017). Genetic alterations in seborrheic keratoses. Oncotarget 8:36639–36649. https://www.oncotarget.com/article/16698/text/

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