Skin cancer

Skin cancer Microchapters
Patient Information
Overview
Historical Perspective
Classification Melanoma Basal cell carcinoma Squamous cell carcinoma of the skin Actinic keratosis Bowen's disease Keratoacanthoma Dermatofibrosarcoma protuberans Merkel cell carcinoma Kaposi's sarcoma Angiosarcoma Cutaneous B cell lymphoma Cutaneous T-cell lymphoma Sebaceous gland carcinoma
Pathophysiology
Causes
Epidemiology & Demographics
Risk factors
Screening
Diagnosis
Treatment
Prevention

Skin cancer
ICD-10	C43-C44
ICD-9	172, 173
ICD-O:	8010-8720
MeSH	D012878

For patient information click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4] Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[5]

Overview

Skin cancer is the malignant growth on the skin which is the most common type of malignancy in Caucasians. Skin cancer generally develops in the epidermis (the outermost layer of skin), so a tumor is usually clearly visible. This makes most skin cancers detectable in the early stages. There are three common types of skin cancer, each of which is named after the type of the skin cell from which it arises. Cancers caused by UV exposure may be prevented by avoiding exposure to sunlight or other UV sources, wearing sun-protective clothes, and using a broad-spectrum sunscreen. Skin cancers are the fastest growing type of cancer in the United States. Skin cancer represents the most commonly diagnosed malignancy, surpassing lung, breast, colorectal and prostate cancer. More than 1 million Americans were estimated to be diagnosed with skin cancer in 2007.

Historical Perspective

• In 1928, sunscreens were first introduced in United States after which they gained tremendous commercial success
• In 1978, US FDA first adopted the efficacy of protection by sunscreens as indicated by the sun protection factor (SPF)
• In 1988, Bestor first identified DNA methyltransferase 1 (DNMT1), which is the primary target of UV radiations in carcinogenic process of skin cancer
• From 1992 to 1994, free American Academy of Dermatology's National Skin Cancer Early Detection and Screening Program was launched which provided broad skin cancer educational information to general public and enabled almost 750,000 free expert skin cancer examinations which mostly found out thin, localized stage 1 melanomas with high projected 5-year survival rate
• From 2001 to 2005, American Academy of Dermatology National Melanoma/Skin Cancer Screening Program was launched which led to the conclusion that HARMM criteria can be used to identify the higher-risk subgroup of skin cancer screening population via assessment of multiple risk factors for MM , which will not only reduce the cost but will also increase the yields for suspected MM in future mass screening initiatives
• In 2007, more than 1 million Americans were estimated to be diagnosed with skin cancer
• In 2014, 6500 new cases of melanoma and 76,100 cases of NMSC were estimated to have occurred in Canada
• In 2016, the estimated number of new cases of skin melanoma was 76,380 which is 4.5% of all new cancer cases
• In 2016, a National Consensus on Sun Safety Messages was developed in Canada in order to promote the uniformity of public health messages
• From 1946 to December 2018, a search for studies related to protection by sunscreen was performed in MEDLINE

Classification

• Skin cancer is broadly divided into melanoma and nonmelanoma types as shown in the following table:

Classification of skin cancer

Skin cancer type	Characteristics
Malignant melanoma	Can occur anywhere in the body involving either even normal skin or any existing mole becoming cancerous later on Signs suspicious for melanoma include: Mole changing in size, color, feel or bleeding Large brownish spot having darker speckles Itchy or burning painful lesion Darker lesions involving fingertips, toes, palms, soles, or mucous membrane lining of nose, mouth, anus or vagina Small lesion having irregular borders & portions with multiple colors such as white, pink, red, blue or blue-black Most dangerous type of skin cancer Fatal if not treated early Comprises only a small portion of all skin cancers	Most common type
Nonmelanoma skin cancers (NMSC)
Basal cell carcinoma (BCC)	Mostly occurs on the sun-exposed areas such as: Face Neck May appear as any of the following: Waxy or a pearly bump Brown scar-like or flesh-colored flat lesion Scabbing or a bleeding sore (heals and returns)	Most common types
Squamous cell carcinoma (SCC)	Mostly involves sun-exposed skin areas such as: Face Ears Hands Unexposed areas to sun are also involved in darker-skinned individuals May appear as any of the following: Red, firm nodule Flat lesion having a crusted, scaly surface Local disfiguration Unlikely to metastasize
Actinic keratosis	Can appear as: Rough, pink, red or brown, scaly, flat or raised patch on the skin Peeling or cracking of lower lip not cured by lip balm or petroleum jelly Most commonly involves: Face Top of the hands
Bowen's disease	Also known as: Bowen's carcinoma Squamous cell carcinoma in situ of skin Intraepidermal carcinoma skin Considered as a slowly growing, very early stage of squamous cell carcinoma of skin Appears as red or brown scaly patch/plaque on the sun-damaged skin Has 3 to 5% risk of developing into invasive squamous cell carcinoma Most commonly occurs in elderly with multiple comorbidities Involves sun-damaged, and poorly healing areas of skin Easily treatable by excision	Rare types
Keratoacanthoma	Benign epithelial tumor Considered as to be a variant of SCC Erupts with an initial rapid growth (like a little volcano) on sun-damaged skin and resolves on its own later on after few months
Dermatofibrosarcoma protuberans	Associated with t(17,22)(q21;q13) Begins as a minor firm area of skin resembling a bruise, birthmark, or pimple May appear as a raised nodule with bleeding 2-5% cases are reported to metastasize
Merkel cell carcinoma	Most commonly involves: Head Neck Trunk Appear as shiny, firm nodules just beneath or on the skin & in hair follicles
Kaposi's sarcoma	Involves the blood vessels of skin Forms purple or red patches on skin or mucous membrane Involves individuals: Having weak immune system such as: AIDS patients Patients on immunosuppressant therapy (after an organ transplant) Young African men Eastern European jewish or Italian older men
Angiosarcoma	Associated with PTPRB/PLCG1 genes mutation Involves: Head Neck Kidney Liver Lung Breast (radiation-induced angiosarcoma) Common clinical manifestations include: Gradually enlarging, painless mass (most common) Skin thickening, erythema, or skin discoloration (primary cutaneous) Lymphedema (secondary angiosarcoma) Pain, edema or other symptoms due to compression of adjacent neurovascular structures
Cutaneous B cell lymphoma	Appears as: Red-brown bumpy rash or Nodules Involves: Head Neck Torso of the body Cutaneous B cell lymphoma is classified into following types: Primary cutaneous marginal zone B-cell lymphoma Primary cutaneous follicle center lymphoma Primary cutaneous diffuse large B-cell lymphoma (leg type) Intravascular diffuse large B-cell lymphoma Plasmacytoma Plasmacytosis
Cutaneous T-cell lymphoma	Manifests as any of the following: Raised or scaly, itchy, round skin patches Skin patches lighter in color than the surrounding skin Lumps on skin (ulcerate or break open) Hair loss Enlarged lymph nodes Intensely itchy, rash-like skin redness over whole body Skin thickening in palms & soles It is further classified into: Mycosis fungoides Sezary syndrome
Sebaceous gland carcinoma	Uncommon Aggressive tumor of sebaceous glands Can occur anywhere but most commonly involves eyelids

Pathophysiology

• Skin cancer is most closely associated with chronic inflammation of the skin

Normal skin function

• Skin is the largest organ of body with following functions:
  • As a physical barrier, it provides protection against:
    • Sunlight
    • Heat
    • Infection
    • Injury
  • Controls the body temperature (provides insulation to the internal body organs)
  • It stores:
    • Water
    • Vitamin D
    • Fat

Normal skin anatomy

• The two main layers of skin include:
  • Outer layer of epidermis (skin cancer starts in this layer), which has following three different kinds of cells:
    • Top layer of epidermis is made up of thin, flat squamous cells
    • Round basal cells are present below the layer of squamous cells
    • Lower epidermal layer has melanin producing cells (melanocytes) which on increased sun exposure lead to more pigment production causing skin darkening
  • Inner layer of dermis

Layers of the epidermis.[1]

Anatomy of the skin showing the epidermis (including the squamous cell and basal cell layers), dermis, subcutaneous tissue, and other parts of the skin.[2]

Diagram of the layers of the epithelial skin layer: the epidermis.[3]

{{#ev:youtube|https://www.youtube.com/watch?v=DnvD6mgSGjg}}

Epigenetics

UVA & UVB have both been implicated in causing DNA damage resulting in cancer by any of the following mechanisms:

• UV radiation induces histone 3 methylation changes in the gene promoters of matrix metalloproteinase 1 and MMP3 in primary human dermal fibroblasts leading to the increased expression of MMP1 and MMP3
• UVB irradiation leads to DNA CpG methylation and transcriptomic changes in following genes & cancer related pathways at the different stages of carcinogenesis:
  • PTEN
  • p53
  • Nrf2
  • p21(Waf1/Cip1)
  • Inflammatory signaling
  • Enf2
  • Mgst2
  • Vegfa
  • Cdk4
• UVA irradiation causes an increase in intracellular reactive oxygen species (ROS), prostaglandin E2 (PGE2), and PGE2 receptors, which leads to decreased expression of transcription factor zinc finger E-box binding homeobox 1(ZEB1) which binds to DNA methyltransferase 1 (DNMT1) promoter and regulates its transcription, thus leading to senescence of DNMT1 in human dermal fibroblasts (HDFs). This causes low methylation level of senescence related proteins p53 thus, increasing its expression, eventually resulting in cellular senescence

UVA exposure to the sun-exposed skin

Suppression of the contact hypersensitivity (CHS) response

Increased intracellular ROS, PGE2, and PGE2 receptors in human dermal fibroblasts

Decreased expression of transcription factor zinc finger E-box binding homeobox 1(ZEB1)

Decreased binding of ZEB1 to DNA methyltransferase 1 (DNMT1) promoter

Senescence of DNMT1 (gene silencer)

This leads to: Low methylation level of senescence related proteins p53, thus, increased expression Hypermethylation of tissue inhibitor of metalloproteinase 2 (TIMP2)

Cellular senescence

• UV radiation leads to overexpression of COX-2 whose end product is prostaglandin E2, involved in skin carcinogenesis
• Overexpression of MiR-211, MiR-217 and miR-377 is associated with suppression of DNMT-1 mediated methylation of p16 and pRb, thus, inducing senescence in human skin fibroblasts
• MicroRNA-152 and -181a modulate the levels of adhesion proteins and extra-cellular matrix components, such as integrin α5 and collagen XVI hence, in this way lead to senescence of human dermal fibroblasts
• Decreased expression of UHRF1 (ubiquitin-like with PHD and ring finger domains 1) is the main initial event in suppressing DNMT1-mediated DNA methylation which increases WNT5A expression resulting in consequent induction of senescence
• MicroRNA‐21 is involved in regulation of ERK/NF‐κB signaling pathway which affects the proliferation, migration, and apoptosis of human melanoma A375 cells by targeting SPRY1, PDCD4, and PTEN

Gross Pathology

• Macroscopically, the tumor is often elevated, fungating, or may be ulcerated with irregular borders
• Malignant melanoma appears as a small lesion having irregular borders & portions with multiple colors such as white, pink, red, blue or blue-black
• Basal cell carcinoma appears as a waxy or a pearly bump, or a brown scar-like or flesh-colored flat lesion, or a scabbing or a bleeding sore that heals and returns
• Squamous cell carcinoma appears as a red, firm nodule or a flat lesion having a crusted, scaly surface
• Bowen's disease appears as a red or brown scaly patch/plaque on the sun-damaged skin
• Merkel cell carcinoma appears as shiny, firm nodules just beneath or on the skin & in hair follicles
• Kaposi's sarcoma appears as purple or red patches on skin or mucous membrane

Microscopic Pathology

• Microscopically, tumor cells destroy the basement membrane and form sheets or compact masses which invade the subjacent connective tissue (dermis)
• In well-differentiated carcinomas, tumor cells are pleomorphic/atypical, but resembling normal keratinocytes from prickle layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central nucleus)
• Their disposal tends to be similar to that of normal epidermis: immature/basal cells at the periphery, becoming more mature to the centre of the tumor masses
• Tumor cells transform into keratinized squamous cells and form round nodules with concentric, laminated layers, called "cell nests" or "epithelial/keratinous pearls"
• The surrounding stroma is reduced and contains inflammatory infiltrate (lymphocytes)
• Poorly differentiated squamous carcinomas contain more pleomorphic cells and no keratinization

Causes

• Skin cancer occurs due to mutations in DNA of skin cells causing them to grow out of control leading to formation of a mass of cancer cells

Epidemiology & Demographics

• Skin cancer is a common condition because of the increased exposure to UV radiation (caused by increasing popularity of sun tanning/sun bathing)
• It is the most common malignancy in Caucasian population
• Individuals with lighter-skin are more vulnerable to get it
• One out of every three new cancers arises from skin in United States
• Incidence of both malignant melanoma (MM) and non-melanoma skin cancer (NMSC) is increasing with MM having an annual increase of 0.6% in individuals >50 years
• In 2014, 6500 new cases of melanoma and 76,100 cases of NMSC were estimated to have occurred in Canada
• In 2016, the estimated number of new cases of skin melanoma was 76,380 which is 4.5% of all new cancer cases
• Annual incidence of melanoma in situ is 9.5% according to some recent epidemiological studies
• National Cancer Registries has reported an underestimation of the incidence of melanoma in certain countries, hence, its incidence may even be higher than actually documented depending upon population-based varying risk factors and discrepancies in national registration systems

Risk factors

Common risk factors for skin cancer include:

Risk factors for the development of skin cancer

Risk factors	Associated features
Excessive sun exposure	Sun bathing Especially early in life can lead to skin damage and even sunburn if skin isn't protected by: Clothing Sunscreen Sun exposure between 10AM and 4PM is considered to be most harmful
Artificial UV exposure	Tanning is the response of skin to excessive UV radiations: Tanning salons Tanning lamps Tanning beds
Fair skin	Less melanin pigment in the skin means less protection from damaging UV radiation Having a fair complexion includes the following: Fair skin that burns and freckles easily, does not tan, or tans poorly Blond or red hair Green, blue, or other light-colored eyes
Genetic predisposition	Congenital Melanocytic Nevi Syndrome is characterized by: Presence of varying sized "nevi" or moles Appear at or within 6 months of birth Nevi larger than 20 mm (3/4") in size are at higher risk for becoming cancerous
Chronic non-healing wounds	Especially burns, known as Marjolin's ulcers (can transform into squamous cell carcinoma)
Prior history of sunburns	History of one or more of the blistering sunburns during childhood or teenage years increases the risk of skin cancer as an adult Sunburns in adult life
High altitude or sunny climate	Increased sunlight exposure occurs to the people living in the areas having: High altitude (i.e. closer to the sun) Warm, and sunny climate (as compared to a colder climate)
Prior chemotherapy	Previous history of chemotherapy puts a person at an increased risk for developing a skin cancer
Moles	Having large number of moles increases the chances of having skin cancer in future Dysplastic nevi which are multiple abnormal irregular moles, have increased tendency to become cancerous
Advanced age	Age >70 years
Precancerous skin lesions	Actinic keratoses increases the risk of having skin cancer and has the following characteristics: Dark pink to brown, scaly, rough patches Involves head, face, and hands Fair-skinned individuals are most commonly affected as their skin is more prone to sun damage
Xeroderma Pigmentosum (XP)	Xeroderma Pigmentosum is an autosomal recessive genetic disorder which leads to decreased ability to repair DNA damage caused by ultraviolet light XP patients are at higher risk for developing melanoma
Radiation exposure	There's an increased risk for development of skin cancer (especially basal cell carcinoma) in individuals with a prior history of radiation therapy for skin conditions such as: Acne Eczema
Personal history of skin cancer	Individuals who have developed skin cancer once are at increased risk for developing it again anytime later in their lives
Exposure to certain substances	Arsenic
Family history of skin cancer	Individuals having a family history of skin cancer especially in parents and siblings are at elevated risk of developing skin cancer themselves
Weakened immune system	Due to: HIV infection (AIDS) Taking immunosuppressant therapy after organ transplantation
Beta-Human Papilloma Virus	HPV infection is associated with increased risk of BCC
Male gender	Being a male is also one of the risk factors for developing skin cancer as compared to the female population
Prolonged skin inflammation	Having a skin inflammation that has lasted for prolonged periods of time also predisposes to the development of skin cancer

Screening

According to different studies going on for so many years, following data is available regarding the different methods/tools and their effectiveness for skin cancer screening:

• From 1992 to 1994, free American Academy of Dermatology's National Skin Cancer Early Detection and Screening Program was launched which provided broad skin cancer educational information to general public and enabled almost 750,000 free expert skin cancer examinations which mostly found out thin, localized stage 1 melanomas with high projected 5-year survival rate
• From 2001 to 2005, American Academy of Dermatology National Melanoma/Skin Cancer Screening Program was launched which led to the conclusion that HARMM criteria can be used to identify the higher-risk subgroup of skin cancer screening population via assessment of multiple risk factors for MM , which will not only reduce the cost but will also increase the yields for suspected MM in future mass screening initiatives
• Melanoma Genetics Program identifies the genetic causes of skin cancer, and also provides genetic counseling to the individuals having a strong family history of melanoma
• Dermoscopy usage improves the ability of primary care physicians to triage lesions which are suggestive of skin cancer and saves from unnecessary expert consultations
• Combination of dermoscopy and short-term sequential digital dermoscopy imaging (SDDI) in a primary care setting doubles the sensitivity for melanoma diagnosis and also leads to >50% chance of reduction in excision or referral of benign pigmented lesions

Diagnosis

The two sentinel features of skin cancer diagnosis are skin examination and subsequent biopsy of the suspected skin lesion. Common history, symptoms, physical examination findings and diagnostic tests are mentioned below:

History and Symptoms

Common sites of involvement

• Primarily involves the sun-exposed areas of skin such as:
  • Scalp
  • Face
  • Lips
  • Ears
  • Neck
  • Chest
  • Arms
  • Hands
  • Legs (especially in women)
  • Eyelids (sebaceous gland carcinoma)
• Can also involve the skin areas very rarely exposed to sun such as:
  • Underneath fingernails or toenails
  • Palm of the hand
  • Sole of the foot
  • Genital region

Common symptoms

• There are a variety of different skin cancer symptoms including crabs or changes in the skin that do not heal, ulcers in the skin, discoloration, and changes in existing moles
• Malignant melanoma appears as a small lesion having irregular borders & portions with multiple colors such as white, pink, red, blue or blue-black
• Basal cell carcinoma appears as a waxy or a pearly bump, or a brown scar-like or flesh-colored flat lesion, or a scabbing or a bleeding sore that heals and returns
• Squamous cell carcinoma appears as a red, firm nodule or a flat lesion having a crusted, scaly surface
• Actinic keratosis appears as either a rough, pink, red or brown, scaly, flat or raised patch on the skin or as peeling or cracking of lower lip not cured by lip balm or petroleum jelly and most commonly involves face and top of the hands
• Bowen's disease appears as a red or brown scaly patch/plaque on the sun-damaged skin
• Keratoacanthoma erupts with an initial rapid growth (like a little volcano) on sun-damaged skin and resolves on its own later on after few months
• Dermatofibrosarcoma protuberans begins as a minor firm area of skin resembling a bruise, birthmark, or pimple
• Merkel cell carcinoma appears as shiny, firm nodules just beneath or on the skin & in hair follicles and mostly involves head, neck and trunk
• Kaposi's sarcoma appears as purple or red patches on skin or mucous membrane
• Angiosarcoma's most common manifestation is a gradually enlarging, painless mass, with other symptoms including skin thickening, erythema, or skin discoloration (primary cutaneous),lymphedema (secondary angiosarcoma), pain, edema or other symptoms due to compressionof adjacent neurovascular structures
• Cutaneous B cell lymphoma appears as red-brown bumpy rash or nodules involving head, neck or torso of the body
• Cutaneous T-cell lymphoma has multiple manifestations including raised or scaly, itchy, round skin patches, skin patches lighter in color than the surrounding skin, lumps on skin (ulcerate or break open), hair loss, enlarged lymph nodes, intensely itchy, rash-like skin redness over whole body, and skin thickening in palms & soles

Physical Examination

• On physical examination, basal cell carcinoma usually looks like a raised, smooth, pearly bump on the sun-exposed skin of the head, neck or shoulders
• Small blood vessels, crusting and bleeding in the center of tumor can be seen sometimes, hence, often mistaken as a non-healing sore
• Squamous cell carcinoma commonly appears as a red, scaling, thickened patch on sun-exposed skin with/without ulceration or bleeding, and can develop into a large mass if left untreated
• Most melanomas appear as brown to black looking lesions
• Signs indicating a malignant melanoma include change in size, shape, color or elevation of a mole
• Appearance of a new mole during adulthood, or new pain, itching, ulceration or bleeding of an existing mole should always be checked as it is suspicious for melanoma

Laboratory Tests

• Dermoscopy usage improves the ability of primary care physicians to triage lesions which are suggestive of skin cancer and saves from unnecessary expert consultations
• Combination of dermoscopy and short-term sequential digital dermoscopy imaging (SDDI) in a primary care setting doubles the sensitivity for melanoma diagnosis and also leads to >50% chance of reduction in excision or referral of benign pigmented lesions

Biopsy

• Skin biopsy (i.e. removal of a sample of suspicious skin for testing) is an essential component of skin cancer diagnosis and by histopathological lab analysis, can determine whether it is a skin cancer or not, and if so, what type of skin cancer it is

Other Diagnostic Studies

• In case of a metastatic stage IV skin cancer such as a large SCC, melanoma, & merkel cell carcinoma, lymph nodes become involved, which requires further testing such as:
  • Sentinel lymph node biopsy
  • Imaging tests for lymph node involvement such as Chest X-ray, CT, MRI, PET scan or ultrasound depending on the site involved
• Eye examination with dilated pupil to look for retina and optic nerve involvement in case of metastasis

Treatment

• Treatment of skin cancer varies depending upon the size, type, depth, location, stage of the tumor, involved body part, and patient’s general health
• Small lesions limited only to the skin surface can easily be cured by simple initial skin biopsy and may not require any further treatment whereas large lesions with metastasis require further treatment options as shown in the table below:

Different treatment options for skin cancer

Treatment option	Description
Cryosurgery/Freezing	Cancer cells are destroyed by freezing them with liquid nitrogen Later on, the dead tissue sloughs off on thawing	For precancerous or small, low-risk, superficial lesions Overall lower cure rates than surgery Done in case of localized disease
Electrotherapy	Electromagnetic therapy uses electrical stimulation to kill cancer cells
Curettage & electrodesiccation or cryotherapy	After removal of most of the growth, layers of cancer cells are scraped away using a device having a circular blade (curet) An electric needle destroys any of the remaining cancer cells Liquid nitrogen can be used in order to freeze the base and edges of the treated area
Photodynamic therapy	Uses combination of laser light and drugs making cancer cells sensitive to light to destroy skin cancer cells
Chemical peel	Chemical solution is put on the skin to dissolve the top layers of cancerous skin cells Used to treat actinic keratosis Also known as: Chemabrasion Chemexfoliation
Other drug therapy	Retinoids are used to treat squamous cell carcinoma of skin Topical drugs used to treat actinic keratosis include: Diclofenac Ingenol
Simple excisional surgery	It includes cutting off the cancerous tissue with a surrounding margin of healthy skin Sometimes, wide excision is done involving excision of extra normal skin around the tumor	Overall higher cure rates Done in case of metastatic disease, larger lesions, recurring or difficult to treat cancer
Mohs micrographic surgery	Uses special training & technique involving the skin removal, layer by layer with subsequent examination of each layer under microscope, until no abnormal cells are remaining Least amount of the surrounding healthy tissue is removed Edges are immediately checked to see if tumor is found Provides best cosmetically favorable results especially on the skin areas with limited excess skin such as face Cure rates are equivalent to wide excision
Shave excision	Abnormal area is shaved off the skin surface using a small blade
Laser surgery	This surgical procedure uses a laser beam as a knife in order to make bloodless cuts in tissue or for removal of a surface lesion such as a tumor
Dermabrasion	Top layer of skin is removed using a rotating wheel or small particles to rub away skin cells
Chemotherapy	Topical chemotherapy including creams or lotions containing anticancer agents can be applied directly to the skin in case of cancers limited to the top layer of skin Systemic chemotherapy can be used to treat skin cancers with metastasis to other parts of the body
Radiation therapy	High-powered energy beams such as X-rays are used to kill cancer cells Used when cancer can't be completely removed via surgery Two types of radiation therapy can be used: External radiation therapy (a machine outside the body is used to send radiation towards the cancer) Internal radiation therapy (radioactive substance is used which is sealed in needles, seeds, wires, or catheters which are placed directly into or near the cancer)
Targeted therapy	Targeted therapy uses signal transduction inhibitor to treat basal cell carcinoma, which includes: Vismodegib Sonidegib
Biological therapy	Also known as: Biotherapy Immunotherapy Immunotherapy uses body's own immune system to kill cancer cells Commonly used immunotherapeutic agents include: Injectable interferon (SCC) Topical imiquimod (BCC)	Done when surgery or radiation therapy has failed to cure skin cancer

Prevention

Although the possibility of skin cancer can't be eliminated completely, but the risk for developing skin cancer can be significantly reduced by acting on the following preventive measures in the first place to decrease the excessive exposure to UV rays:

Primary preventive measures for skin cancer

Preventive method	Details
Avoiding sunburns and suntans	Avoid sun exposure: During the middle of the day, usually from 10 AM to 4 PM, especially in North America Even during cloudy days or winters
Wearing protective clothing	Wear the following while being in the outdoor environment: Tightly woven, dark clothing Shirts with long sleeves Broad-brimmed hats Pants that fully cover the legs (avoid shorts) Photoprotective clothing Sunglasses (the ones which block both types of UV radiation i.e. UVA & UVB)
Wearing SPF sunscreen	Wear a sunscreen generously year-round, even during winters & cloudy days It should be at least SPF 30 It should be broad-spectrum blocking both UVA and UVB rays Cover all the exposed areas including the back of hands, neck, lips, tip of ears Reapply it every 2 hours & more often after swimming or if perspiring a lot
Avoiding tanning beds	Tanning beds use the lights that emit UV rays which can increase the risk for skin cancer
Being aware of sun-sensitizing medications	Over-the-counter drugs and common prescriptions including antibiotics may have tendency to increase the sensitivity of skin Always ask the doctor or pharmacist about the possible side effects of any medications before taking them Take extra precautions to protect the skin by staying away from the sun,in case if the medications being used have tendency to increase the skin sensitivity to sunlight
Checking skin regularly and reporting any new or unusual skin changes to the doctor	Examine the skin often for any new skin growths or changes in existing moles, bumps, birthmarks, & freckles Check face, ears, neck, and scalp by using the mirror Examine the chest, trunk, top & underside of arms and hands Examine both the front and back of legs, and feet, including soles and spaces between the toes Also check the genital area and area between the buttocks
Watching dysplastic nevi (abnormal irregular multiple moles) regularly	Watch dysplastic nevi (abnormal irregular multiple moles) regularly as they have increased tendency to become malignant
Reducing the exposure to ultraviolet (UV) radiation, especially during the early years of life	Prior history of radiation exposure (both UV or artifical radiation therapy for acne or eczema) leads to increased chance for development of basal cell carcinoma

Effectiveness of sunscreen in prevention of skin cancer

Multiple studies have been carried out to find out the effectiveness of sunscreen in protection against skin cancer:

Different sunscreen recommendations and recommendations' grading according to Canadian Task Force on Preventive Health Care (CTFPHC) GRADE System

Sunscreen property	Recommendation	Grade of Recommendations
SPF (Sun Protection Factor)	An ideal sunscreen should have the following properties: Broad-spectrum Both UVA & UVB filters Atleast SPF 30	Strongly recommended
Water resistance	Sunscreen providing water-resistance for 40-80 minutes must be worn in following conditions: Water immersion Excessive sweating Contact with sand Physical contact causing increased skin friction
Organic vs inorganic sunscreens	Whether the components of sunscreen are organic or inorganic, the recommended sunscreen must be broad spectrum with both UVA & UVB filters
Lip protection	Whole lip should be generously covered by high-SPF (>/= 30) and reapplication of lip sunscreen
Sunscreen application	Sunscreen is recommended to be applied according to the following guidelines: Should be applied liberally (approximately 45 ml) to all the exposed areas Strong reapplication within a period of 8 hours is mandatory only after activities that may remove the sunscreen layer such as sweating, swimming, or friction Should be applied before any sun exposure and at least 20 minutes before the water activities
Patient education on sunscreen	Patients should be educated about the meaning of SPF and its effectiveness
Sunscreen safety	Sunscreens have a favorable risk-benefit profile, hence, are considered to be safe overall There is still a risk of following few complications due to sunscreen application in some people: Photoallergy (most common, but quite rare) Reproductive toxicity
Sunscreen benefits	Prevents photoaging Prevents melanoma and non–melanoma skin cancer
Sunscreen vehicle	Highest SPF and water resistance properties of sunscreen can be obtained by using a water-in-oil emulsion formulation for sunscreens	Weakly recommended
Expiry date	Avoid using sunscreens past their manufacturer-specified expiry date/recommended period after opening Sunscreens should be stored at normal room temperature in order to ensure their proper stability

US FDA monograph list of active ingredients of sunscreen

Type of filter	Name of UV filter		Concentration in percentage
Organic UVB Filters	Cinnamates	Octinoxate (octyl methoxycinnamate, Parsol MCX)	7.5%
		Cinoxate	3%
	PABA derivatives	15% Para-aminobenzoic acid (PABA)	15%
		Padimate O (octyl dimethyl PABA)	8%
	Salicylates	Octisalate (octyl salicylate)	5%
		Homosalate	15%
		Trolamine salicylate	12%
	Others	Octocrylene	10%
		Ensulizole (phenylbenzimidazole sulfonic acid)	4%
Organic UVA Filters	Benzophenones	Oxybenzone (benzophenone-3)	6%
		Sulisobenzone (benzophenone-4)	10%
		Dioxybenzone (benzophenone-8)	3%
	Others	Butyl methoxydibenzoylmethane (avobenzone, Parsol 1789)	3%
		Meradimate (menthyl anthranilate)	5%
Inorganic Filters	Titanium dioxide		25%
	Zinc oxide		25%

Measurement of UV protection afforded by sunscreens and clothing

Measurement system	SPF (Sun protection factor)	UVA‐PF (UVA‐protection factor)	UPF (Ultraviolet protection factor)
Definition	Minimal erythema dose (MED) of UVB radiation causing erythema after applying 2 mg/cm2 of sunscreen to skin divided by the dose producing 1 MED on unprotected skin	The dose of UVA causing observable pigment darkening (minimal pigment dose [MPD]) after applying 2 mg/cm2 of sunscreen to skin divided by the dose producing 1 MPD on unprotected skin	The ability of fabrics to prevent UV radiation transmission via absorption and/or reflection and highly dependent on fabric type, color, porosity, thickness, weight, and other factors
Developed for	Sunscreens	Sunscreens	Clothing
Global acceptance	International	United States only	International
UV wavelengths protected	UVB	UVA	UVA, UVB
Examples	SPF 2 protects against 50% of UVB SPF 8 protects against 88% of UVB SPF 15 protects against 93% of UVB SPF 30 protects against 97% of UVB SPF 50 protects against 98% of UVB	UVA‐PF1 protects against 20–39% of UVA UVA‐PF2 protects against 40–69% of UVA UVA‐PF3 protects against 70–95% of UVA UVA‐PF4 protects against >95% of UVA	UPF cotton 5–10 UPF denim 1700

Knowing individual skin type and using the right sunscreen accordingly

Skin type by the Fitzpatrick Scale	Skin color	Skin tone or other common descriptors	Sun exposure effects	Recommended sunscreen SPF
I	Pale white	Pale or albino, freckles common (Celtic)	Always burns Never tans	30+
II	White	Light or fair (European)	Always burns Rarely tans
III	White	Light‐intermediate (Dark European)	Sometimes burns Sometimes tans	15+
IV	Light brown	Olive with/without brown tint (Mediterranean)	Tans easily Burns less
V	Dark brown	Brown	Tans easily Rarely burns
VI	Black	Black	Does not burn

Skin Cancer Prevention Facial-Aging Mobile App

app

Related Chapters

• Cancer
• Mohs surgery

References

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