Skin and Melanoma

Chapter 37 Skin and Melanoma ______

Anatomy and Physiology:

 Skin is the largest organ of the body (22 sq. ft.; 10-12#) . Regulates the body temperature through perspiration . Acts as a barrier . Participates in production of vitamin D- absorption of calcium in GI tract . Provides receptors for external stimuli- heat, cold, pressure, touch

 Layers: . Subcutaneous layer: a layer of areolar connective tissue and adipose tissue that lies beneath the dermis and contains nerves and blood vessels . Dermis: the deeper layer of the skin composed of connective tissue that contains blood and lymphatic vessels, nerves and verve endings, sweat glands and hair follicles. . Basement layer . Epidermis: the extremely thin outer layer of the skin composed of four to five distinct layers of cells. No blood or lymphatics- no spread. o Stratum basale:  Keratinocytes: any one of the cells in the skin that synthesizes keratin. . Keratin: an extremely tough, waterproof protein substance in hair, nails and horny tissue.  Melanocytes: the melanin-forming cell- all races have approximately the same amount. . Melanin: the pigment that gives color to the skin (amount produced determined by genetics) and hair and serves as protection from ultraviolet light. A tan is a response by the body to damage caused by UV light- stimulates melanocytes in the stratum basale to make melanin to protect the skin.  Merkel’s cells- touch o Stratum spinosum: keratinocytes absorb melanin o Stratum granulosum: keratinocytes produce keratohyalin- precursor to keratin o Stratum lucidum: found in thick skin o Stratum corneum: dead layer, squamous cells filled with keratin ______

Types of Cancers

 Melanoma: a dark pigmented malignant tumor arising from the skin. . Tend to develop from melanocytes which grow in clusters to from a mole or nevus. o Nevus: a benign, localized cluster of melanocytes arising in the skin, usually early in life. . Most lethal form of cancer . Commonly found on legs of women, trunk and face of men  Nonmelanomas: . Basal cell carcinoma: a slow-growing, locally invasive but rarely metastasizing neoplasm derived from stem cells of stratum basale of the epidermis or hair follicles. (most common cancer in humans-5X more common than SCC) . Squamous cell carcinoma: a faster growing cancer than the basal cell type with a higher propensity for metastasis; arises from the more nature keratinocytes of the upper layers of the epidermis. This type of nonmelanoma skin cancer can arise anywhere on the body but is especially common on sun-exposed areas such as the head, neck, face, arms, and hands.

 Less common skin cancers: . Mycosis fungoides: a chronic, progressive T-cell lymphoma of the skin. Initially the disease resembles eczema or other inflammatory dermatoses, in advanced cases, ulcerated tumors and infiltrations of lymph nodes may occur. o Can be localized for a long time o Can treat with TBI with electrons or topical nitrogen mustard. . Kaposi’s sarcoma: arise from vascular tissue, nodular purple lesions common in AIDS patients, may be treated with RT, poor prognosis . Merkel’s cell carcinoma: firm, nontender, pink-red nodular lesions that tend to recur after surgery; can spread to lymph nodes and distantly. ______

Epidemiology

Epidemiology: Skin Cancer in General:  Incidence of skin cancer related to: . Geography:  Equator- sun’s rays intense and direct;  Elevation- less ozone to filter out rays . Skin type:  Fair skin- lack melanin  Albinos, freckles, light eyes, Xeroderma pigmentosum . History of skin cancer:  Exposed to same carcinogens  Weakened immune system to fight skin cancer . Gender:  Men: increase in both melanoma and nonmelanoma except legs with nonmelanoma.

 Skin cancer is the most common type of human malignancy  The incidence of both melanoma and nonmelanoma is on the rise  Death rates for melanomas have increased over the past 40 years; while death rates for nonmelanomas have decreased.  Nonmelanomas are 30 times more common, but 3 times as many people die each year from melanoma compared to nonmelanoma  At least 50% of those who reach the age of 65 will develop some type of skin cancer. Epidemiology: Melanoma  Melanoma incidence has increased approximately 7% per year worldwide  Melanomas are responsible for 1.3% of all cancer deaths

Epidemiology: Nonmelanoma  Nonmelanoma’s incidence has increased by 65% since 1983. . The healthy tan . Clothing trends . Ozone layer depletion: filters out UV rays (1% decrease = 2.6% increase in cancer rates) ______

Etiology

Etiology- Skin Cancer in General:  Ultraviolet light, specifically from the sun, is involved in 90% of skin cancers  Exposure to arsenic (cigarettes, soil, water)  Exposure to occupational or therapeutic radiation  20% increase in risk in previously treated area (SCC likely)  Latent period up to 50 years  Squamous cell carcinomas are 2/3 of the radiation-induced lesions and have a 10% mortality rate

Etiology- Melanoma:  B-K syndrome aka Dysplastic nevi syndrome: . Occurrence of melanoma in one or more first or second degree relatives . Large number of moles, (50+) some of which are atypical and often variable in size . Moles that demonstrate certain histological features  Family history: 8X increased chance  Number of moles

Etiology- Basal Cell Carcinomas:  Xeroderma pigmentosum: a rare disease of the skin starting in childhood and marked by disseminated pigment discoloration, ulcers, cutaneous and muscular atrophy and death.  Basal cell nevus syndrome: a genetically linked condition that appears during the late teens . Multiple BCCs of the skin . Cysts of the jaw bones . Pitting of the palms and soles . Skeletal anomalies (particularly the ribs)

Etiology- Squamous Cell Carcinoma:  Human papilloma virus (HPV)  Immunosuppression- transplant, lymphoma/leukemia  Thermal or electrical burns  Scars or inflammatory conditions  Hydrocarbons from coal and petroleum  Area of chronic drainage- fistulas, sinuses  Smoking (lip) Melanoma:

Clinical Presentations:  70% occur as a change in a preexisting nevus/mole  ABCD rules of detection . Asymmetry . Border: uneven/smooth . Color: non-uniform/uniform . Diameter: greater than 6 mm/less than 6 mm  Other changes to look for: . Change in color- red, white, blue . Change in surface- scaly, flaky, bleeding, oozing . Change in texture- hard, lumpy, elevated . Change in surrounding skin- pigmentation, swelling, or redness around skin . Change in sensation- unusual pain or tenderness in a mole

Pathology:  If diagnosed with melanoma; also need to know . Depth of penetration . Mitotic rate . Subtype . Growth patterns: most melanomas start with a radial (horizontal) growth phase followed by a vertical growth phase. o Superficial spreading melanoma- radial growth, most common subtype 70% o Nodular melanoma- more common in men, lesions tend to be raised, lack radial growth phase, invade early and frequently show ulceration when advanced, 15% of all lesions o Lentigo malignant melanomas- aka Hutchinson’s freckles, 5% of all lesions o Acral lentginous melanomas- 10% of all lesions, occur mainly on palms, soles, nail beds or mucous membranes especially in Asian and African American patients

Staging:  Clark system: categorized melanomas based on level of invasion through the epidermis and dermis  Breslow system: categorizes melanomas based on tumor thickness from top to bottom found to be a little more accurate than Clarks system *When melanomas metastasize, usually go to lungs, liver, bone and brain

Prognostic indicators:  Thickness  Depth of invasion  Ulceration  Lymph node status  Gender, age  Location of primary: tumors located on the extremities (excluding feet), have a better prognosis than tumors on the head and neck, which have a better prognosis than a tumor on the trunk Treatment:  Surgery: the only treatment for cure . Prior to 1970’s, wide excision with 5 cm margins were standard, but no evidence that wide excision increased survival . Margin size now determined by o Thickness o Site o Potential side effects o Chance of recurrence

Other treatments:  Isolated limb perfusion with chemo and hyperthermia: extremity isolated with a tourniquet while the blood in the limb circulates though a caching that pumps, oxygenates, and heats it(melanoma cells cannot survive above 105.8 degrees, large doses of chemotherapy delivered.  Chemotherapy  Hormone therapy: some melanomas contain estrogen receptors, respond to antiestrogen therapy.  Immunotherapy- . Interferons: proteins that activate and enhance the tumor killing ability of monocytes and produce chemicals toxic to cells . Interleukins: act as co-stimulators and intensifiers of immune responses.

Radiation Therapy  Melanoma is radioresistant, so RT used for palliation of mets or as an adjuvant to surgery  If used at all, 500 cGy fractions usually needed to overcome SLD repair  Greatest role of RT is to palliate mets or recurrent disease . Bone and brain mets palliated with 3000-4000 cGy ______

Nonmelanoma:

Precancerous lesions:  Actinic (solar) keratoses: a warty lesion with areas of red, scaly patches occurring on the sun-exposed skin of the face or hands of older, light-skinned individuals.  Arsenical keratoses: hard corn-like masses on palms and soles  Bowen’s disease: a precancerous dermatosis or form of intraepidermal carcinoma characterized by the development of pink or brown papules covered with a thickened, horny layer.  Keratoacanthoma: a papular rapid growing lesion that appears suddenly on a sun-exposed area; dome shaped mass filled with a keratin plug that can resemble squamous cell carcinoma. It is benign and usually subsides spontaneously within 6 months.

Staging:  Since BCC and SCC are considered very curable if treated early, there is no staging system used commonly. Treatment:  Treatment for BCC and SCC based on: (goal is eradication of tumor with good cosmesis) . Previous treatments . Location of cancer . Risk of recurrence/ mets . Volume of tissue invasion

Surgery:  Best option when scarring is acceptable and quick results are wanted  If margins are clear after removal, no further treatment is necessary  Moh’s surgery: a surgical method in which the tumor is removed one layer at a time and examined microscopically. It is used for tumors in high-risk sites for recurrence and those with aggressive histologic subtypes. Known for its 96% success rate. Slow and expensive.  Curettage & electrodessication: tumor scooped out and cauterized . Good for BCC and early SCC  Cryosurgery: freezes cells using liquid nitrogen or carbon dioxide, may have to be repeated several times  Photodynamic therapy: a photosensitizing agent is injected and absorbed and retained in cancer cells, laser light causes reaction which destroys cells.

Radiation Therapy  Effective for small tumors where cosmetic results are important (lips, nose, eyelid, face, and ears)  Electrons, kilovoltage x-rays, or brachytherapy implants (surface molds)  Advantages: . Normal tissue sparing  Disadvantages: . Cost . Multiple treatments . Late skin changes (scarring, necrosis, chronic radiation dermatitis)

 Kilovoltage VS. electron treatment . Factors to consider: o Field size: kilovoltage allows a smaller field size to be treated (important for next to critical structures) o Dmax: better with kilovoltage, Dmax of electrons is a function of field size, location of secondary collimation and surface contour. o Deep tissue dose: electrons fall off faster than kilovoltage, so less dose to underlying structures with electrons o More bone absorption with kilovoltage

 Technical components: . Cones- both electrons and kilovoltage use cones . Filters- for kilovoltage . Cutouts/ lead shields o For electron treatments: placed in the cone o Orthovoltage: placed directly on patient  Radiation Dose . Varies according to size and penetration of lesion: can treat with large fraction size because it’s a superficial treatment o Small BCC: 3500-4000 cGy o Large (over 5 cm BCC or most SCC): 5000 - 6000 cGy  Margins: . 1cm margin around tumor for small BCC . 2 cm margin around all others

 Special considerations: . Bolus: to increase dose to surface or fill in for tissue deficit o Lips- wax covered lead to protect teeth and gums o Nose- wax covered lead to protect nostrils o Eyes- lead eye shields internal or external o Ears- wax behind ears

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Basal Cell Carcinoma

Clinical Presentation:  Smooth, red, or milky lumps with pearly borders  Multiple telangiectases  80% occur on head and neck, especially T-zone

Pathology:  Usually don’t grow deeper than epidermis, no chance of metastasis  Can get large if not treated and invade bone or cartilage  Four main subtypes: curable if caught early . Nodulated-ulcerated BCC . Superficial BCC . Morphea-form, or sclerosing: scab like . Cystic BCC

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Squamous cell carcinoma

Clinical Presentation:  Scaly, crusty, slightly elevated lesions, can be ulcerated or nodular  80& of UV induced lesions occur on arms, head, and neck Pathology:  More likely to metastasize than BCC (3 – 10% chance)  Patients with high risk factors more likely to metastasize . Etiology: developing in areas of: o Scar tissue o Post-radiation o Inflammation . Poor differentiation ______

Side effects of Radiation Therapy Treatment:

Melanomas and nonmelanomas:  Acute:  Erythema: acute radiation effect, manifested by redness and inflammation of the skin or mucous membranes, is caused by capillary congestion, caused by dilation of the superficial capillaries. . Hyperpigmentation: increased production of melanin . Dry and moist desquamation: shedding of the epidermis . Temporary hair loss . Decreased oil and sweat gland function  Chronic or late effects . Skin usually doesn’t return to normal o Fibrosis o Hypopigmentation o Telengiectasia: dilation of the surface blood vessels caused by the loss of capillary tone, resulting in a fine spider-vein appearance on the skin surface. . Necrosis possible in high dose cases ______

Prevention of skin cancer:

 90% of skin cancers are preventable with proper precautions  Limiting UV exposure is key to prevention . Avoid sun between 10 am and 2 pm . Avoid reflected sun from sand, snow, cement, water . Avoid tanning beds . Even on a cloudy day, 20-80% of UV rays still get though . Wear hats and appropriate clothing ______

Sunscreen

 Even with a high SPF, need to limit sun exposure  Apply 15 minutes before exposure, reapply every two hours or after swimming  The UV index is 0-15, the higher the number, the shorter amount of time it will take to burn.