Basic knowledge for USMLE 1

Natalia Stelson

Statistic facts
- 3-7% of all tumors - amount of cases grows in white population, but in nonwhite is stable -65% caused by sun exposure -5-12%of patient with melanoma have first degree relatives with melanoma - 1/3 melanomas from nevus

Risk factors
Amount of nevi ( typical and atypical) Cutaneous pigmintation phenotype Skin phenotype Family and personal story of skin cancer Exposure sun in childhood Intermittent recreational sun exposure in adult

Premelanoma
Atypical melanocitic proliferation (Lentigo maligna Hutchinson melanotic frecle and ect)

Rare forms of melanoma

Dermoplastic melanoma Nerotrophic melanoma Resembling melanocytic nevi ( nevoid) Arising in congenital nevi Small sell melanoma Balloon melanoma Myxoid melanoma

Other types of melanoma

Solar melanoma sites greatest sun exposure Acral melanoma in places with glabrous skin (without hair) palm, sol (subungunales, digits. under the nail Nodular melanoma any localization progressed from nodule or papule ( blue, dark blue or pink) Amelanotic melanoma

Amelanotic melanoma
Color: pink, ivory, white. Can resemble scar Desmoplastic melanoma Can be acral, lentigo or subungunal Better prognosis, less mts Highly reccurent (spindle shape of cell)

Features of melanocytes
Low proliferetion potential Melanoblasts migrate to the their position from neural crest almost fully differentiated and stay there almost all life Melanocytes are resistant to apoptosis ( have antiapoptotic gene BCL2) Have very long life span (decades) so, mutation can accumulate by years

Factors, that determinate skin pigmentation

Rate synthesis of melanin by melanocytes Rate of transfer melanosomes from melanocytes to keratocytes Activity of 2 enzymes in melanocytes (tyrosine related protein 1(TYRP 1) and dopachrome tauomerase (DCT) or other name tyrosine-related protein 2 (TRP 2) ! Amount melanocytes in different race almost the same. All difference in melanins synthesis and transport

Way melanin gets keranocyte

1. Melanocytes are dendritic cells. Point of their dendrites place of releasing melanosomes for their transfer to keratocytes 2. Keratocytes have receptors protease activated receptor 2 (PAR2) 3. PAR2 activate keratocytes phagocytosis of melanosomes ! Expression of PAR 2 by keratocytes depends of UV. UV- more PAR 2 more melanosomes phagocytized more

Function of melanin in skin

- Protects against of reactive oxygen species, produced by UV. This decreases damage of DNA, proteins and lipids - Photoprotective for fibroblats , preventing their aging ! Increasing production of melanin is sign of damage of DNA

Genetic
MC1R highly polymorphic gene (gives diversity of pigmintation) Mutation in p16 cause rise susceptibility CDKN2A alternative reading frame, that disable p53

Symptoms
(mnemonic)

Asimetric Border (uneven) Color (unsolid) Diameter (more 6 mm) + for nodular forms Elevated Firm Growning

One of possible reason, among other, is change in character of cell junction: melanocyte connected with keratocytes by gap junction through E-catherins. It creates epidermal-melanin unit (36 keratocytes : 1 melanocytes) Melanoma produces N-catherins. This protein is connectes not with keratocytes, but with fibroblasts and other melanocytes. In theory the same situation with endothelium, who has a great deal of adhesion proteins used for immune reaction. Among them exist number of receptors that can open junctions between endothelial cells for immune cells. Cancer cells can trick endothelium.

Early metastases

Sites of metastasis.
Lymph Nodes: 70% to 75% Other areas of the skin, fat and muscle: 65% to 70% Lungs and area between the lungs: 70% to 87% Liver and gallbladder: 54% to 77% Brain: 36% to 54% Bone: 23% to 49% Gastrointestinal tract: 26% to 58% Heart: 40% to 45% Pancreas: 38% to 53% Adrenal glands: 36% to 54% Kidneys: 35% to 48% Spleen: 30% Thyroid: 25% to 39%