# Skin **Skin Layers** * Stratum cutaneum #### Diseases Acquired melanocytic nevi → Dysplastic nevi → Melanoma\ Actinic keratosis → Squamous cell carcinoma in situ\ Seborrheic keratoses → Basal cell carcinoma **Acquired melanocytic nevi** * more prominent in pregnancy * flat or dome * uniform * nevi are neoplasms because they have acquired BRAF or NRAS mutations, growth is stopped by p16 1NK4a **Dysplastic nevi** * often >0.5cm * flat macules * slightly raised with 'pebbly' surface **Melanoma** * ACE → Assymetry, Color variation, irregular Edges * change in size, shape, color * variations in color * irregular borders * often notched borders * HMB-45 melanocyte marker, used with sentinel nodes * radial growth pattern (favourable), epidermis and superficial dermis * vertical growth pattern, nodule, metastatic potential * Breslow thickness = deepest intradermal thickness (depth of lesion) **Actinic keratosis** * “cutaneous horn” * sharply defined, scaling plaques * carcinoma in situ if contained to the BM * keratin production and ulceration, may be signs of invasive types * poorly differentiated ones use IHC for keratin to diagnose **Seborrheic keratoses** * round, coin-like, waxy plaques * look for small, pore-like ostia impacted with keratin * appears often with and may progress to BCC * Leser-Trelat sign → appearance in large numbers due to paraneoplastic syndrome **Basal Cell Carcinoma** * slow growing * pearly, smooth-surfaced papule with associated telangiectatic vessels (prominent dilated subepidermal blood vessels) * most common malignancy worldwide * locally aggressive, metastasis rare * associated with the Hedgehog pathway mutation * lifelong life exposure to sun * microscopically resemble normal epidermal basal cell layer * not encountered on mucosal surfaces because they only arise from epidermis or follicular epithelium **Squamous Cell Carcinoma** * highly atypical cells at all levels of the epidermis * SCC in situ appear as sharply defined, red, scaling plaques * nodular, ulceration are signs of invasion * lifelong life exposure to sun * can progress from actinic (sun) keratosis * chemical, thermal burns, HPV with immunosuppression * cutaneous SCC has potential for metastasis but less so than mucosal SCC * mucosal are much more aggressive (oral, pulmonary, esophageal) * [TP53](https://notes.jjjp.ca/pathology/disease/tp53) by DNA damaged by UV light, and activated HRAS mutations * HRAS and loss-of-function mutations in Notch receptions, which transmit signals that regulate the orderly differentiation of normal squamous epithelia * UV light may also have transient immunosuppressive effect on skin by impairing antigen presentation by Langerhans cells **Cowden syndrome** * multiple benign lesions that resemble their organ of origin, hamartomas * mutation in the PTEN gene * [1 in 200 000 people](https://ghr.nlm.nih.gov/condition/cowden-syndrome#genes) **Muir-Torre syndrome**