Melanoma: Key aspects and characteristics

• Skin Pathology details the study of skin disorders.
• Most photos are from Copyright © 2017, by Elsevier Inc. All rights reserved.

Objectives of Skin Pathology

• Students will acquire knowledge on the different skin disorders.

The Skin

• The skin is the largest organ in the body.
• The skin consists of three layers: the epidermis, the dermis and the subcutaneous tissue.
• Hair and nails are modified forms of skin.

Function of the Skin

• It provides protection by preventing infectious agents from entering the body.
• It shields internal organs, muscles, nerves, blood vessels, and other structures from the sun's ultraviolet rays.
• The skin prevents the loss of essential fluids and substances.
• Skin contains blood vessels that expand and contract to regulate body temperature in response to a person's body temperature.
• Sweat is a natural response to feeling hot, thus the evaporation of sweat on the skin causes a reduction in body temperature.
• It conserves heat for the body's vital organs.
• It senses painful and pleasant stimuli.
• Nerve cells make the skin sensitive to pressure and touch.
• The skin contains specialized nerve endings that stimulate the nerve and endocrine systems.
• The skin is a minor source of waste disposal.
• Sweat glands excrete waste products such as urea, a byproduct of protein metabolism; therefore, eliminating them from the body.
• Skin characteristics, such as texture, temperature, color, and clarity, can provide information about a person's general health and suggest a number of disorders.
• For example, jaundice (a yellow color in the skin) may be a sign of liver disease or anemia (paleness caused by a condition characterized by decreased red blood cells).

Cells that compose the Skin

• Squamous epithelial cells (keratinocytes)
• Melanocytes
• Dendritic cells interact with the systemic immune system
• Lymphocytes
• Neural end organs and axonal processes
• Neuroendocrine Merkel cells reside within the epithelial basal cell layer
• Sweat glands
• Hair follicles harbor protected niches of epithelial stem cells

Freckle (Ephelis)

• Freckles are the most common pigmented lesions of childhood in lightly pigmented individuals.
• Freckles are 1 to several mm in diameter, tan-red or light brown macules that appear following sun exposure.
• Hyperpigmentation of freckles results from increased amounts of melanin pigment within basal keratinocytes

Melanoma

• Melanomais the deadliest of all skin cancers, strongly linked to acquired mutations caused by exposure to UV radiation in sunlight.
• Melanomas can be found in the skin, oral cavity, anogenital mucosal surfaces, esophagus, meninges, and eye.
• More than 60,000 cases of melanoma are found, and more than 8000 deaths are expected each year.
• Melanomas evolve over time from localized skin lesions to aggressive tumors that metastasize and are resistant to therapy, early recognition and complete excision are critical.
• The most consistent clinical signs are changes in the color, size, or shape of a pigmented lesion.
• The borders of melanomas are irregular and often notched, not smooth, round, and uniform as in melanocytic nevi.
• Important warning signs, sometimes called the ABCs of melanoma, are asymmetry, irregular borders, and variegated color.
• 10% to 15% of melanomas are inherited as an autosomal dominant trait
• Familial cases are associated with germline mutations affecting the genes that regulate cell-cycle progression or telomerase
• The majority of melanoma is sporadic and related to ultraviolet radiation (UVR) damage from sun exposure.
• UVR is associated strongly with DNA damage, leading to a high rate of point mutations Melanomas most commonly arise on sun-exposed surfaces, particularly the upper back in men and the back and legs in women
• Lightly pigmented individuals are at higher risk than are darkly pigmented individuals
• The CDKN2A gene is mutated in approximately 40% of pedigrees with autosomal dominant familial melanoma
• Molecular lesions in sporadic melanoma leads to aberrant increases in RAS and PI3K/AKT signaling
• Reactivation of telomerase, the enzyme activity that preserves telomeres and protects cells from senescence, has long been known to be important in cancer

Melanoma Prognosis

Favorable Prognosis

• Once a melanoma is excised
• Tumor depth (the Breslow thickness) matters
• Number of mitoses is a factor
• Evidence of tumor regression (presumably due to the host immune response)
• The presence and number of tumor infiltrating lymphocytes (TILs)
• Gender
• Location (central body or extremity)
• Tumor depth of less than 1.7 mm,
• No or very few mitoses,
• Brisk TIL response,
• Absence of regression
• Female gender helps
• Location on an extremity is favorable
• Most melanomas initially metastasize to regional lymph nodes, additional prognostic information may be obtained by performing a sentinel lymph node biopsy
• Microscopic involvement of a sentinel node by even a small number of melanoma cells (micrometastases) confers a worse prognosis

Seborrheic Keratosis

• One of the most common types of noncancerous (benign) skin growths in older adults.
• Most people develop at least one seborrheic keratosis during their lives.
• A seborrheic keratosis appears as a brown, black or pale growth on the face, chest, shoulders and back.
• The growth has a waxy, scaly, slightly elevated appearance.
• Occasionally they appear singly, but multiple growths are more common.
• Seborrheic keratoses do not become cancerous, but can look like skin cancer.
• Skin growths are normally painless and require no treatment.
• Activating mutations in the fibroblast growth factor receptor-3 (FGFR3) gene are found in many sporadic seborrheic keratoses and are thought to drive the growth of the tumor.
• The exact cause of seborrheic keratoses is unclear.
• They tend to run in some families, so genetics may play a role.
• Ultraviolet (UV) light may also play a role in their development since they are common on sun-exposed areas, such as the back, arms, face and neck.

Actinic Keratosis

• A skin condition characterized by rough, scaly patches on the skin of your face, lips, ears, back of your hands, forearms, scalp and neck.
• The cause is frequent or intense exposure to ultraviolet (UV) rays, typically from the sun.
• Actinic Keratosis is precancerous.
• Actinic Keratosis is also known as solar keratoses, grow slowly and usually cause no signs or symptoms other than patches or small spots on your skin appearing in older adults.
• Left untreated, about 2 percent to 5 percent of actinic keratoses develop into a serious form of skin cancer called squamous cell carcinoma.
• You're most likely to develop actinic keratosis if you have one or more of these risk factors: frequent sun exposure or sunburn, pale skin, blond or red hair, especially paired with blue, hazel or green eyes, freckling or burning when exposed to sunlight, or a weak immune system because of chemotherapy, chronic leukemia, AIDS or organ transplant medications

Basal Cell Carcinoma

• The most common form of skin cancer.
• The most easily treated and the least likely to spread.
• Can cause extensive damage to surrounding tissue and bone if they're not removed, though it is rarely fatal
• Often takes decades to develop
• Basal cell carcinomas have a high recurrence rate; recurring within five years.
• Caused by long-term exposure to ultraviolet (UV) radiation from sunlight

Squamous Cell Carcinoma

• Found increasingly in people younger than 40, earlier it was commonly found in older adults
• It is highly curable and rarely causes further problems.
• If untreated, may destroy healthy tissue around the tumor, spread to the lymph nodes or other organs, and occasionally prove fatal.
• Results from prolonged exposure to ultraviolet (UV) radiation, either from sunlight or from tanning beds or lamps.
• Risk factors: a lifetime spent in the sun, fair skin
• Men are far more likely to develop it than women
• Other risk factors: a personal history of skin cancer, weakened immune system, rare genetic disorder (xeroderma pigmentosum), smoking, and skin inflammation or injury (exposure to coal or arsenic)

Atopic Dermatitis

• A chronic inflammatory skin disease.
• Commonly appears in the first year of life.
• Affects 10% of all children.
• Associated with allergies.
• Characterized by high levels of IgE and sensitization to food allergens
• Begins with a rash (acute dermatitis)
• Possible secondary infections
• Resolves spontaneously

Contact Dermatitis

• Inflammation of the skin that results from direct contact with substances like soap, cosmetics, jewelry, and weeds.
• Symptoms include a red, itchy, non-contagious rash; it can be uncomfortable.
• Treatment consists primarily of identifying what's causing the inflammation.
• The rash usually resolves in two to four weeks as long as there is no contact with the agent causing inflammation
• Can use self-care measures, such as wet compresses and anti-itch creams help soothe skin and reduce inflammation. Itching may be severe
• It can be identified from dry, red patches and blisters with draining fluid in involved skin in severe cases, skin rash limited to the exposed area
• It falls into two categories: irritant contact dermatitis (common) or allergic contact dermatitis

Rosacea

• A chronic facial disorder of middle age and older patients.
• Can be a form of acne without the comedones.
• Associated to migraine and H. pilori.
• The symptoms include redness of the cheeks and nose, pimples, nasal hypertrophy (rhynophyma)
• Controlled with medications like Ivermectin Cream; however, it has no cure

Psoriasis

• A skin disease that affects the life cycle of skin cells.
• Normally, new cells take about a month to move from the lowest skin layer where they're produced to the outermost layer where they die and flake off.
• In psoriasis, the entire life cycle takes days, resulting in cells rapidly building up, causing thick silvery scales and itchy, dry, red patches that are sometimes painful.
• A persistent (chronic) disease and may be disabling, especially when associated with arthritis. No cure exists, but treatments may offer significant relief.
• Self-care measures, such as using a nonprescription cortisone cream and exposing skin to small amounts of ultraviolet light, can improve symptoms.

Types of Psoriasis

• Plaque psoriasis is the more common form, it causes causes dry, red skin lesions (plaques) covered with silvery scales which can occur anywhere on the body, including the genitals and the soft tissue inside of the mouth.
• Nail psoriasis causes fingernails and toenails to have pitting, abnormal nail growth and discoloration; nails may become loose and separate from the nail bed (onycholysis).
• Scalp psoriasis has red, itchy areas with silvery-white scales

Herpes Zoster

• Anyone who has had chicken pox can develop herpes zoster.
• Also known as shingles or zoster.
• Caused by the same virus as chicken pox.
• Around 20% of people develop Zoster if they have had chicken pox.
• Most patients only develop zoster usually once.
• It isn't clear what reactivates the virus and spreads the shingles
• A temporary weakness in immunity may cause the virus to move along nerve fibers and multiply toward the skin.
• It is more common in people over the age of 50.
• Illness, trauma, and stress can all trigger zoster.
• Zoster is less contagious than chicken pox.
• Newborns and those with decreased immunity are at the highest risk.
• Shingles only occurs after someone already had chicken pox when the virus is reactivated in certain nerve cells after developing chicken pox
• If someone contracts the virus and never had chicken pox they will develop chicken pox and not shingles

Complications of Herpes Zoster

• The most common problem of herpes zoster is post-herpetic neuralgia with the pain, numbness, itching, and tingling lasting for months or years.
• Bacterial infection can develop in the blisters, delaying healing
• Treat early to avoid scarring from sores
• An infection involving zoster lesions can lead to scarring
• Zoster in the eye that is not promptly treated can lead to complications such as glaucoma, scarring, and blindness

Warts

• Common warts are local growths in the skin caused by Human Papilloma virus (HPV) infection and is contagious
• Locations are often found at the back of fingers/toes/knees, the bottom of the foot as plantar warts, on the face/legs and other areas of the body; often in large numbers in what is called "plane" warts.
• Periungual warts are around or under the nail.
• Filiform warts typically appear as a single long stalk, often on the face.

Wart treatments

• Salicylic-acid preparations dissolves the protein (keratin).
• Nonprescription freezing methods using aerosol wart treatments will freeze warts at a temperature of minus 70 F (minus 57 C).
• Duct tape can "suffocate" them by covering the area being used all the time and removed for only a few hours per week until the wart is gone

Tinea Corporis

• Superficial dermatophyte infection characterized by either inflammatory or noninflammatory lesions on the skin, except the scalp, groin, palms, and soles).
• Caused by dermatophytoses: Trichophyton, Microsporum, and Epidermophyton.
• Dermatophytes preferentially inhabit the nonliving, cornified layers of the skin, hair, and nail, which is attractive for its warm, moist environment conducive to fungal proliferation.

Tinea Pedis

• Athlete's foot infection, caused by a fungus.
• Tinea pedis thrives in warm humid conditions.
• Most common in young adult men.
• Most frequently due to: Trichophyton (T.) rubrum, T. interdigitale and Epidermophyton floccosum.

Ulcers

• A skin ulcer is an open sore often accompanied by the shedding of inflamed tissues.
• Ulcers can be caused by trauma, damage to heat / cold, poor circulation, corrosive materials and/or reduced blood supply in certain areas due to pressure.

Pressure Ulcers

• Bedsores can quickly develop and progress rapidly.
• Often difficult to heal, they are caused by sustained pressure on the body
• They're especially common in areas that aren't well padded with muscle or fat that lie just over a bone, such as your spine, tailbone (coccyx), shoulder blades, hips, heels and elbows.
• Blood flow is restricted because the skin and the underlying tissues are trapped between bone and a surface.
• This deprives tissue of oxygen and nutrients, causing irreversible tissue damage and in some cases death.

This flashcard covers key aspects and characteristics of melanoma, including hyperpigmentation, prognosis factors and the role of UV radiation. Explore cellular processes, genetic mutations, and prognostic indicators, vital for understanding melanoma development and management.