PIGMENTATION



Melanocytes - cells hidden in the basal layer that secrete the dark pigment melanin into skin cells. Melanin (made from Tyrosine in organelles called melanosomes) makes skin dark, and it absorbs harmful UV light. Melanocytes are derived from neural crest cells. 

Vitiligo - ↓melanocytes. AI destruction of melanocytes → splotchy albinism. Easy to spot in people of color. In pale people, vitiligo only materializes when they fail to tan in splotchy areas. No inflammation (no pain or redness). Since it’s autoimmune, vitiligo is managed with steroids. 


Albinism - ↓melanin. AR absence of pigmentation. Usually due to the loss of an enzyme (Tyrosinase) in the melanin production process. They have a normal number of melanocytes, but those melanocytes aren’t very good at their jobs. Albinism often involves the eyes as well as the skin. Without the protective keratin, they have a very high risk of sunburns, Melanoma, SCC and BSC. 


Freckle - ↑melanosomes. Hyperplasia of Melanosome organelles (not Melanocytes). Small brown macule that darkens with sun exposure. 


Melasma - ↑melanin. Mask-like hyperpigmentation of cheeks. Caused by Estrogen (eg, pregnancy and birth control). Pronounced in women with dark complexions. Prevent w/ sunscreen. Treat w/ Hydroquinone (Tyrosinase inhibitor)

MELANOMA

The bad skin cancer


Nevus (Mole) - benign Melanocyte proliferation. Dark papules. Super common. Can be congenital (hair grows out of these). Usually acquired in the following stages: 

     Junctional Nevus - melanocytes grow along the BM. Common in kids.   

          Compound Nevus - Junctional Nevus that grows down into dermis

               Intradermal Nevus - Compound Nevus that loses its Junctional component. Common in adults.


Melanoma - malignant Melanocytes. Deadly! Caused by UV-B light (usually). Melanomas look like moles with: 

          Asymmetry

          Borders that are irregular

          Color that are not uniform

          Diameter > 6 mm

          Evolution

The key feature of metastatic melanoma is invasion past the BM. Phases of Melanoma growth: 

          Radial - horizontal growth along the BM and into the epidermis

          Vertical - downward growth, deep into the BM. Poor prognosis here. 

There are 4 major subtypes of Melanoma:

          Lentiginous - radial growth, good prognosis

          Superficial Spreading - most common, mostly radial growth, superficial = it doesn’t go deep, good prognosis

          Nodular - early vertical phase, nodule on the skin, poor prognosis

          Acral Lentiginous - Arises on palms / soles, often in people of color. Unrelated to UV light. Most aggressive. Killed Bob Marley.

Sometimes, melanoma can be treated with Pembrolizumab, a monoclonal Ab that binds to PD-1 (Programmed Death Receptor). PD-1 is expressed by sneaky cancer cells, and it diminishes the immune response by telling killer T cells to kill themselves (programmed death). But in most cases, the treatment consists of the usual surgical excision plus or minus chemo and radiation.


Genetics stuff 

Melanoma is associated with a BRAF mutation. The V600E mutation is vulnerable to Vemurafenib

S-100 (+) indicates neural crest cell descendants

HMB-45 is an antibody that is expressed in melanoma, used for diagnostics