Seborrheic Keratosis

Overview

Definition

Seborrheic keratosis (SK) is a benign 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 tones
• Sex: No differences

Etiology

• 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 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 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):
  • Rough-surfaced SKs more common than smooth-surfaced: submillimeter keratinous horn pearls on surface (differentiate from 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 melanin pigmentation is present.
• Many histologic variants but no clinical significance (e.g., hyperkeratotic, irritated with pronounced squamous metaplasia)

Clinical presentation

• Raised 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.

Diagnosis and Management

Diagnosis

Physical exam:

• Classic clinical appearance
• Typically on trunk, face, or upper extremities
• Horn cysts can be seen with 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 or 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 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 tumor, derived from the malignant transformation of melanocytes: Melanomas present as growing pigmented 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 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 or sometimes 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 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 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 (AN, dysplastic nevus): Atypical nevus is a benign lesion but is a phenotypic marker for an increased risk of melanoma, especially if there are multiple lesions and/or if there is a positive family history of melanoma. An AN may develop into 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 during an attempt to compress and elevate it (“retraction,” or “dimple sign”). Diagnosis is usually clinical, and treatment is typically not required.