Actinic Keratosis (Clinical)

Overview

Definition

• Synonym: solar keratosis
• Precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett Esophagus 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 lesion or growth caused by sun damage

Epidemiology^[3,4]

• Most common cutaneous lesion with cancerous potential (can 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) (SCC))
• > 40 million people in the United States develop 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 each year.
• Men > women 

Risk factors^[3,4]

• Ultraviolet (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
  • Usually from extensive sun exposure
  • Causes mutations in 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, which prolong their survival and stimulate the proliferation of atypical cells
• History of sunburns
• Light 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
• Age > 50 years
• Immunosuppression
• Geographic location: 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 is more common in Australia than in the United States or Northern Europe due to increased sun exposure.
• Genetic disorders
  • Xeroderma pigmentosum Xeroderma pigmentosum A rare, pigmentary, and atrophic autosomal recessive disease. It is manifested as an extreme photosensitivity to ultraviolet rays as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA. Lentigo Maligna:
    • Autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance condition 
    • Mutations in genes Genes 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. DNA Types and Structure cause a defect in DNA repair mechanisms DNA repair mechanisms Although DNA fidelity is highly protected, DNA can still be damaged by a number of environmental factors, reactive oxygen species, and errors in DNA replication. DNA repair is a continuous process in which the cell corrects the damage. The cell has multiple mechanisms it can use to repair DNA. DNA Repair Mechanisms. 
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with UV light UV light That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-uv or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-uv or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. Bullous Pemphigoid and Pemphigus Vulgaris sensitivity (e.g., severe sunburns) 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 cancer development. 
  • Bloom’s syndrome:
    • Autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance condition (rare)
    • Caused by mutations in the BLM 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 
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with erythematous 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 rash Rash Rocky Mountain Spotted Fever on sun-exposed areas, small stature, immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome, and predisposition to cancer.

Clinical Presentation

Description of lesions^[2,5]

• Appearance:
  • Usually < 1 cm in diameter
  • Single or multiple 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
  • Tan-brown, red, or flesh/skin-colored
  • Progress from small macules/papules with a sandpaper-like texture Texture Dermatologic Examination → scaly, erythematous patches Patches Vitiligo/plaques
• Areas affected (sun-exposed areas):
  • Face and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess
  • Arms and  dorsum of hands
  • Legs
  • Bald scalp
• Adjacent 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 may show signs of solar damage Solar Damage Actinic Keratosis ( field cancerization Field Cancerization Actinic Keratosis):
  • Dry 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
  • Hyperpigmentation Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. Malassezia Fungi 
  • Telangiectasias Telangiectasias Ataxia-telangiectasia
  • Atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation
• The lesions are usually asymptomatic, although tenderness, stinging sensation, or pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) may be present.

Clinical course^[2,4,5]

• 20%–30% of the lesions undergo spontaneous regression Regression Corneal Abrasions, Erosion, and Ulcers each year but may reappear.
• Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship experience persistence of the lesions with no alterations.
• Progression to invasive SCC:
  • Occurs in up to 20% of untreated cases (Note: Reported rate in the literature varies widely.)
  • 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 > 1 cm² ( 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 patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes) is predictive of invasive or in situ SCC in 1½ years

Variants^[2]

• Hypertrophic 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: thick, adherent scales Scales Dry or greasy masses of keratin that represent thickened stratum corneum. Secondary Skin Lesions (accumulation of keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis) on an erythematous base
• Atrophic 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: a smooth, nonpalpable lesion without scale Scale Dermatologic Examination
• Actinic cheilitis Actinic Cheilitis Actinic Keratosis:
  • Affects the lower lip 
  • Presents as a dry, thickened, scaly papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes 
  • May progress to SCC
• 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 with cutaneous horn:
  • A benign Benign Fibroadenoma keratinous growth that resembles a horn/cone
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma recommended as it may transform into SCC
• Pigmented 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:
  • Hyperpigmented macules or patches Patches Vitiligo
  • Can have lateral growth and enlarge beyond 1 cm
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma needed to distinguish from lentigo maligna Lentigo Maligna Lentigo maligna is melanoma in situ, a precancerous lesion that may progress to an invasive melanoma (specifically lentigo maligna melanoma subtype). This condition typically occurs in sun-damaged areas (e.g., face and neck) of elderly patients. Lentigo Maligna

Diagnosis

Diagnosis is usually made clinically by inspection Inspection Dermatologic Examination and palpation Palpation Application of fingers with light pressure to the surface of the body to determine consistency of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. Dermatologic Examination (rough, sandpaper-like texture Texture Dermatologic Examination). Additionally, clinicians may employ:^[3,4,7,8]

• Dermoscopy Dermoscopy A noninvasive technique that enables direct microscopic examination of the surface and architecture of the skin. Seborrheic Keratosis:^[7,9]
  • Handheld device with transilluminating light source and magnifying optics
  • Primarily used to evaluate pigmented lesions
  • Findings in 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:
    • Erythematous pseudo-network (“strawberry” appearance)
    • Follicular openings 
    • Surface scale Scale Dermatologic Examination
    • Linear, wavy vessels
• Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:^[7,8] 
  • Shave biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: The lesion with surrounding thin layer of 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, up to the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions, is removed. 
  • Punch biopsy Punch Biopsy Actinic Keratosis: differs from a shave biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma in that it reaches the subcutaneous layer and 3 mm is the typical diameter of the sample
  • Indications for biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
    • Uncertain clinical diagnosis 
    • Suspicion of neoplasm (SCC)
      • > 1 cm in diameter
      • Induration Induration Dermatologic Examination
      • Ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers
      • Tenderness
      • Rapid growth
      • Non-responsive to adequate therapy
    • Low threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction for immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Histopathologic findings:^[2,4]
    • Cytologic atypia Atypia Fibrocystic Change in the lowermost layers 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 
    • A lack of full-thickness atypia Atypia Fibrocystic Change 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
    • No basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN) invasion
    • Parakeratosis Parakeratosis Persistence of the nuclei of the keratinocytes into the stratum corneum of the skin. This is a normal state only in the epithelium of true mucous membranes in the mouth and vagina. Actinic Keratosis (retention of the nuclei in the stratum corneum Stratum corneum Skin: Structure and Functions)
    • Solar elastosis Solar Elastosis Lentigo Maligna (thickened blue-gray elastic Elastic Connective Tissue: Histology fibers in the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions as a result of chronic sun damage)
    • Melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis in cases of pigmented AKs
    • May have coexisting melanocytic atypia Atypia Fibrocystic Change

Management

Management may vary depending on practice location. The following information is primarily from US and UK clinical guidelines. Choice of therapy may be determined by the number of lesions, location, patient comfort and preference, clinician Clinician A physician, nurse practitioner, physician assistant, or another health professional who is directly involved in patient care and has a professional relationship with patients. Clinician–Patient Relationship experience, and availability.

Prevention^[5,7,8]

Prevention consists of the use of sunscreen Sunscreen Chemical or physical agents that protect the skin from sunburn and erythema by absorbing or blocking ultraviolet radiation. Melanoma and sun protection.

Treatment of head and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess lesions

Single or a few discrete lesions (lesion-directed therapy):^[5,7,8]

• 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 (preferred):
  • Use of liquid nitrogen Liquid Nitrogen Molluscum Contagiosum administered by spray or contact
  • Quick, inexpensive, office-based procedure
  • Indicated for flat or hypertrophic lesions that are not suspicious for cancer
  • Use 2 freeze-thaw cycles for hypertrophic lesions.
  • Disadvantage: cannot obtain specimen for pathologic diagnosis (perform if diagnosis is clinically certain)
• 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 followed by electrodesiccation Electrodesiccation Seborrheic Keratosis is used as an alternative therapy for flat lesions.
• Shave removal followed by electrodesiccation Electrodesiccation Seborrheic Keratosis or excision is used for hypertrophic lesions.
  • The specimen is sent for pathologic evaluation (for lesions suspicious for cancer).

Multiple lesions/ field cancerization Field Cancerization Actinic Keratosis (field-directed therapy):^[5‒8]

• Topical fluorouracil Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Bowen Disease and Erythroplasia of Queyrat 5% cream or solution (preferred; also available as 0.5%, 1%, and 4%):
  • 1–2 times a day for 4 weeks until inflammatory response reaches erosion Erosion Partial-thickness loss of the epidermis Generalized and Localized Rashes stage; complete healing may not be evident for 1–2 months.
  • Mechanism of action: decreases cell proliferation by inhibiting thymidylate synthase Thymidylate synthase An enzyme of the transferase class that catalyzes the reaction 5, 10-methylenetetrahydrofolate and dump to dihydrofolate and dtmp in the synthesis of thymidine triphosphate. Purine and Pyrimidine Metabolism
  • Causes erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, blistering, and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
  • Avoid around the eyes.
  • May add calcipotriol 0.005% to enhance efficacy of topical fluorouracil Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Bowen Disease and Erythroplasia of Queyrat 5%
• Topical imiquimod Imiquimod A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial carcinoma, basal cell; and actinic keratosis. Hypertrophic and Keloid Scars 5% cream:
  • Applied before bedtime twice a week for 4 months
  • Mechanism of action: produces inflammatory reaction ( cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response)
  • Causes erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), and erosions Erosions Corneal Abrasions, Erosion, and Ulcers
  • Avoid around the eyes.
• Topical tirbanibulin 1% ointment:
  • Mechanism: synthetic inhibitor of tubulin Tubulin A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagellum; cilia; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120, 000 and a sedimentation coefficient of 5. 8s. It binds to colchicine; vincristine; and vinblastine. Flucytosine, Griseofulvin, and Terbinafine polymerization and Src kinase signaling
  • Approved for field treatment of 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 on the face and scalp
  • Apply once daily to an area up to 25 cm² for 5 days.
• Photodynamic therapy Photodynamic Therapy Actinic Keratosis ( PDT PDT Actinic Keratosis):
  • Application of a photosensitizer agent, aminolevulinic acid Aminolevulinic acid A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. It is used as a photochemotherapy for actinic keratosis. Heme Metabolism 10% gel, followed by narrow-band red light illumination
  • Mechanism of action: The agent is cytotoxic Cytotoxic Parvovirus B19 when activated by light energy.
  • Causes stinging, tingling Tingling Posterior Cord Syndrome, and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
• Sequential Sequential Computed Tomography (CT) treatment:
  • Used for multiple hypertrophic lesions
  • 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 is used for individual lesions, followed by topical fluorouracil Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Bowen Disease and Erythroplasia of Queyrat.

Treatment of other body sites^[5,6,8]

• Sites with thicker 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: dorsal hands, forearm Forearm The forearm is the region of the upper limb between the elbow and the wrist. The term “forearm” is used in anatomy to distinguish this area from the arm, a term that is commonly used to describe the entire upper limb. The forearm consists of 2 long bones (the radius and the ulna), the interosseous membrane, and multiple arteries, nerves, and muscles. Forearm: Anatomy, legs
• Sequential Sequential Computed Tomography (CT) treatment:
  • 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 followed by topical fluorouracil Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Bowen Disease and Erythroplasia of Queyrat
  • Gentle 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 followed by PDT PDT Actinic Keratosis

Other field-ablation treatments^[5,6,8]

• Topical diclofenac Diclofenac A non-steroidal anti-inflammatory agent (nsaid) with antipyretic and analgesic actions. It is primarily available as the sodium salt. Nonsteroidal Antiinflammatory Drugs (NSAIDs) 3% in hyaluronan gel:
  • Lower efficacy (28%–40%) than other topical treatments
  • Apply twice daily for 60–90 days.
• Dermabrasion Dermabrasion The mechanical planing of the skin with sandpaper, emery paper, or wire brushes, to promote reepithelialization and smoothing of skin disfigured by acne scars or dermal nevi. Actinic Keratosis:
  • For large areas
  • A handheld specialized instrument removes stratum corneum Stratum corneum Skin: Structure and Functions.
  • Painful; requires sedation and analgesia Analgesia Methods of pain relief that may be used with or in place of analgesics. Anesthesiology: History and Basic Concepts
• Chemical peels:
  • Often used on the face
  • Trichloroacetic acid 35% is applied topically.
  • Medium-depth peel causes stinging pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and visible exfoliation (up to 1 week).
• Laser resurfacing: multiple treatments required

Differential Diagnosis

• 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): a cutaneous malignancy Malignancy Hemothorax most commonly found in sun-exposed sites. Unlike 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, the atypical cells of in situ carcinoma involve the entire 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, and invasive SCC invades beyond the basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN).
• Seborrheic keratosis 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 tumor in middle-aged and elderly adults and presents as a sharply demarcated, exophytic, skin lesion that may be tan or black and has a “stuck-on” appearance. Seborrheic Keratosis: a benign Benign Fibroadenoma neoplasm consisting of 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 occurring commonly in the elderly. A seborrheic keratosis 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 tumor in middle-aged and elderly adults and presents as a sharply demarcated, exophytic, skin lesion that may be tan or black and has a “stuck-on” appearance. Seborrheic Keratosis usually has a sharply demarcated, round, stuck-on appearance on 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.
• Basal cell Basal Cell Erythema Multiforme carcinoma (BCC): a 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 arising from the basal cell Basal Cell Erythema Multiforme layer 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 Basal Cell Erythema Multiforme carcinoma is the 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 and usually presents as slowly growing “pearly papules” with telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency (prominent, dilated subepidermal blood vessels). 
• Seborrheic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema): a chronic inflammatory dermatosis characterized by the presence of greasy, red (inflamed) 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 affecting the scalp (as dandruff Dandruff Excessive shedding of dry scaly material from the scalp in humans. Seborrheic Dermatitis), posterior aspect of the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, and the forehead Forehead The part of the face above the eyes. Melasma. The etiology is uncertain, but the condition appears to be linked to increased sebum Sebum The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. Infectious Folliculitis production and possibly colonization Colonization Bacteriology 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. Skin: Structure and Functions by fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology of the genus Malassezia Malassezia Malassezia is a lipophilic yeast commonly found on the skin surfaces of many animals, including humans. In the presence of certain environments or triggers, this fungus can cause pathologic diseases ranging from superficial skin conditions (tinea versicolor and dermatitis) to invasive disease (e.g., Malassezia folliculitis, catheter-associated fungemia, meningitis, and urinary tract infections). Malassezia Fungi.