Melanocytes and Disorders of Pigmentation

Question 1

Define melanocytes

Answer 1

cells responsible for formation of the melanosome. Neural-crest derived cells that migrate into epidermis and hair follicles during embryogenesis. From the dorsal side of the neural crest, melanoblasts migrate and differentiate around week 8 of development.

Question 2

Define melanosome

Answer 2

organelles that synthesize melanin

Question 3

Define melanin

Answer 3

pigment, skin color resulting from several colored pigments (melanin is one, hemoglobin and carotenoid the others).

Question 4

Depigmentation

Answer 4

complete loss of pigment, depigmented lesions appear milk white

Question 5

hypopigmentation

Answer 5

reduced epidermal pigment due to decreased melanocytes or decreased melanin. Appear off-white.

Question 6

leukoderma

Answer 6

general term encompassing depigmentation and hypopigmentation.

Question 7

hyperpigmentation (melanoderma)

Answer 7

increase in melanin deposition

Question 8

ceruloderma

Answer 8

gray, slate, or blue discoloration arising from an increase in the number of melanocytes.

Question 9

What are the only melanocytes not derived from the dorsal portion of the neural crest?

Answer 9

retinal pigments in the eye, from outer layer of optic cup.

Question 10

Describe the necessary components for melanocyte migration and survival.

Answer 10

c-KIT gene for receptor for steel factor on melanocytes and melanoblasts. Upon binding of steel factor to KIT, phosphorylate and begin a signal transduction cascade, causing melanocytes proliferation and migration.

Question 11

In what level of skin do melanocytes reside?

Answer 11

basal layer of the epidermis.

Question 12

Epidermal melanin unit

Answer 12

association of 1 melanocyte to 30-40 keratinocytes, based on its long cellular processes.

Question 13

Describe the sexual and racial differences in the number of melanocytes.

Answer 13

None! Difference in the shape and activity of melanosomes. Darker people have large, dark, singly dispersed, oval melanosomes. Lighter people have fewer, smaller, clustered spherical melanosomes.

Question 14

Key enzyme in melanosome biosynthesis

Answer 14

tyrosinase, catalyzes multiple steps in melanin synthesis, varying the amount produced.

Question 15

Factors that influence melanogenesis proteins include:

Answer 15

MSH, endothelin-1, and UV light.

Question 16

The two major forms of melanin

Answer 16

eumelanin (brown-black) and pheomelanin (yellow-red), concentrations influenced by MSH binding to melanocortin-1 receptor.

Question 17

Factors that increase eumelanogenesis

Answer 17

elevated MSH, thyroid hormone, estrogen, progesterone, and increased ACTH

Question 18

Effect of UV exposure on melanocytes

Answer 18

increase size of melanocytes and increase tyrosinase activity. Chronic sun exposure leads to a 2-3x increase in number of melanosomes.

Question 19

UV radiation may ______ transcription of tyrosinase gene and ______ number and/or activity of MC1-R on melanocytes

Answer 19

increase, increase.

Question 20

Clinical presentation of vitiligo

Answer 20

depigmented patches, especially around the mouth, eyes, nose, hands, and genitals. May demonstrate Koebnerization (development after a trauma). Photoprotection important.

Question 21

Pathology of vitiligo

Answer 21

an autoimmune inflammatory skin disease that leads to the destruction of melanocytes. Complete absence of melanocytes in histopathology section. May develop other autoimmune diseases (alopecia areata, hypothyroidism, pernicious anemia)

Question 22

Clinical presentation of piebaldism

Answer 22

White forelock in 85-90%, patterned depigmentation of midline. Found at birth, persists throughout life.

Question 23

Pathology of piebaldism

Answer 23

autosomal dominant pattern, resulting from mutation in c-KIT gene in a group of cells, so failure to migrate from midline.

Question 24

Pityriasis Alba clinical presentation

Answer 24

ill-defined, hypopigmented round patches, occasionally with overlying scale. Common in pts w/ atopic dermatitis. No tx: uses sunscreen and lotion to improve appearance.

Question 25

Albinism clinical presentation

Answer 25

autosomal recessive lack of pigmentation in hair, skin, and eyes. Leads to white, yellow, or red-brown skin pigmentation. Persists throughout life. Optic issues of nystagmus, photophobia, and diminished acuity.

Question 26

Pathology of albinism

Answer 26

defect in gene encoding tyrosinase, leading to complete absence of pigment and puts patient at risk for skin cancer.

Question 27

Clinical presentation of melasma

Answer 27

"mask of pregnancy" w/ patchy, dark pigment deposition w/ ill-defined boarders on photo-exposed areas of face, arms, and chest.

Question 28

Pathology of melasma

Answer 28

stimulation of melanin synthesis by increased levels of estrogen and progesterone. Tx: photoprotection, stop taking oral contraceptives.

Question 29

Pathology associated with cafe-au-lait macules

Answer 29

etiology unknown, common in 2% of all newborns, 33% of black neonates. Associated with NF-1, an autosomal dominant condition.

Question 30

Clinical presentation of cafe-au-lait macules and NF-1

Answer 30

uniformly-pigmented light brown macules and patches with sharp borders. >6 CALM sign of NF-1. Other symptoms: rubbery skin colored neurofibromas, axillary freckling, plexiform neurofibromas, yellow-brown papules of the iris (Lisch nodules), optic gliomas, and skeletal abnormalities.

Question 31

Describe the indications and use of a Wood's lamp.

Answer 31

UV light source at wavelength 365 nm to evaluate hyper- and hypopigmented skin. Helpful when diagnosing vitiligo. Depigmented skin accentuates, hypopigmented skin doesn't, accentuates pigment in the epidermis, but not dermal pigment (for hyperpigmentation). Used to predict success of bleaching agents (works if only on the epidermis, not the dermis).

Question 32

Tx of vitiligo and other de- or hypopigmentation

Answer 32

stim melanocyte proliferation and melanin production. Topical corticosteroids, calcineurin inhibitors and phototherapy to reduce inflammation and stim repigmentation from melanocytes around hair follicles. May do surgical transfer, but cosmetic result varies. Sunscreen and hats to prevent skin darkening.

Question 33

Tx of hyperpigmentation (ex: melasma)

Answer 33

Directed towards the destruction of melanocytes or melanin. Topical bleaching agents, such as hydroquinone and azelaic acid used as skin lightening. Response varies by depth and density of pigment.