Seborrheic Keratosis

Overview

Definition

Seborrheic keratosis (SK) is a benign Benign Fibroadenoma 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. Skin: Structure and Functions tumor Tumor Inflammation consisting of proliferating immature keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions.

Epidemiology

• Seborrheic keratoses are the most common benign Benign Fibroadenoma tumors in middle-aged and older adults.
• Most adults will develop at least 1 SK in their lifetime.
• Age group prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 
  • 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. Skin: Structure and Functions tones
• Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria: 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 Oncogenes Genes whose gain-of-function alterations lead to neoplastic cell transformation. They include, for example, genes for activators or stimulators of cell proliferation such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of ‘v-‘ before oncogene symbols indicates oncogenes captured and transmitted by retroviruses; the prefix ‘c-‘ before the gene symbol of an oncogene indicates it is the cellular homolog (proto-oncogenes) of a v-oncogene. Carcinogenesis: fibroblast growth factor Fibroblast growth factor A family of small polypeptide growth factors that share several common features including a strong affinity for heparin, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family. X-linked Hypophosphatemic Rickets receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors 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 Malignancy Hemothorax
  • Possibly due to hypersensitivity to a growth factor (GF) from the tumor Tumor Inflammation (e.g., epidermal GF or alpha-transforming GF)
• Cumulative UV radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma 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. Papillomavirus (HPV) infection: inconsistent evidence

Pathophysiology and Clinical Presentation

Pathogenesis

• Clonal expansion of somatically mutated cells (not epidermal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation):
  • Growth is driven by mutations in oncogenes Oncogenes Genes whose gain-of-function alterations lead to neoplastic cell transformation. They include, for example, genes for activators or stimulators of cell proliferation such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of ‘v-‘ before oncogene symbols indicates oncogenes captured and transmitted by retroviruses; the prefix ‘c-‘ before the gene symbol of an oncogene indicates it is the cellular homolog (proto-oncogenes) of a v-oncogene. Carcinogenesis, most commonly FGFR3 and PIK3CA.
  • Genetically stable (unlike malignant tumors)
• Lack malignant potential, possibly owing to:
  • Lack of tumor Tumor Inflammation suppressor gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations
  • FGFR3 stimulation of the differentiation transcription factor Transcription factor Generic term for proteins necessary for transcription Regulation of Transcription FOXN1

Morphology

• Sites: hair-bearing surfaces only (e.g., trunk, head, neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, 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 Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions
  • 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 Exophytic Retinoblastoma proliferative lesion, composed of small keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions entirely within epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions, without cytologic atypia Atypia Fibrocystic Change; similar to basal cells of normal epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions
• “Horn pseudocysts”: round intralesional cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change 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 String Sign Hypertrophic Pyloric Stenosis”).
• 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 Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation)

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. Skin: Structure and Functions 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 Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema).

Diagnosis and Management

Diagnosis

Physical exam:

• Classic clinical appearance
• Typically on trunk, face, or upper extremities
• Horn cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change 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: Anatomy lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy.

Dermoscopy:

• Milia cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change, comedo-like openings
• Cerebriform pattern (ridges and fissures)

Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:

• If diagnosis is uncertain and malignancy Malignancy Hemothorax 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 (BCC)

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. Skin: Structure and Functions type:
  • Cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma: 
    • Most common method, particularly for flat or thin lesions
    • Minimal postoperative wound care needed
    • Avoid in dark-skinned individuals (may cause hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi)
  • Curettage Curettage A scraping, usually of the interior of a cavity or tract, for removal of new growth or other abnormal tissue, or to obtain material for tissue diagnosis. It is performed with a curet (curette), a spoon-shaped instrument designed for that purpose. Benign Bone Tumors/shave excision: can submit to pathology for diagnosis
  • Electrodesiccation: alone or followed by curettage Curettage A scraping, usually of the interior of a cavity or tract, for removal of new growth or other abnormal tissue, or to obtain material for tissue diagnosis. It is performed with a curet (curette), a spoon-shaped instrument designed for that purpose. Benign Bone Tumors
  • Lasers: many types
  • 40% hydrogen peroxide Hydrogen peroxide A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. Myeloperoxidase Deficiency: modest efficacy only

Differential Diagnosis

• 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: 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. Skin: Structure and Functions tumor Tumor Inflammation, derived from the malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology of melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions: 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. Skin: Structure and Functions lesions, raised or flat, usually with irregular borders and color variegation. Diagnosis is established with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. 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: Actinic keratoses are precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett’s Esophagus lesions that affect sun-exposed areas and consist of atypical/dysplastic keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions that do not occupy the complete thickness of the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions. 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 (SCC) 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 (BCC). Diagnosis can be established on the basis of the clinical appearance and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Actinic keratoses can be managed with excision.
• 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 (BCC): 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. Skin: Structure and Functions cancer, arising from the basal keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions of the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions: 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 (BCC) 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 Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Management is with surgical excision.
• 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 (SCC): 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. Skin: Structure and Functions cancer: 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 (SCC) usually presents as a firm, erythematous, keratotic plaque Plaque Primary Skin Lesions or papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes. Diagnosis is established with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Treatment is usually surgical excision, but can involve radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma or topical chemotherapy Chemotherapy Osteosarcoma.
• 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 Benign Fibroadenoma 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 Family History Adult Health Maintenance 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 Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Excision may be required if diagnosis is in doubt.
• Dermatofibroma (DF): a common, benign Benign Fibroadenoma, 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 Nodule Chalazion 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. Skin: Structure and Functions during an attempt to compress and elevate it (“retraction,” or “dimple sign”). Diagnosis is usually clinical, and treatment is typically not required.