7 - Skin Flashcards
What does dysfunction cause to the skin?
Leads to hair loss, wrinkles, blisters
Conditions: toxin ingestion, diabetes, SLE
What layers is the skin composed of?
E (HSS)
E (CMM)
Epidermal layer
- hair folicles
- sweat glands
- sebaceous glands
Epidermal layer + superficial dermis
- cornified squamous epithelial cells of the stratum corneum
- melanin-containing dendritic melanocytes
mid-epidermal dendritic Langerhans cells
Explain the cutaneous immune system
N-AIA
A. Non-activated
B. Innate
C. Adaptive
A. No inflammation, skin populates with immune cells (stationary + transitory) that survey environment and are primed for response
- langerhans cells, dermal dendritic cells, dermal fibroblasts
- granulocyte + monocyte
B. Innate response to epithelial injury or antigen presentation activates the resident immune cells that then recruit nonspecific effector cells (neutrophils and eosinophils)
- granulocyte + monocyte effector cell recruitment
C. Adaptive response from antigen presented in major histocompatibility complex that specifically recognised by T cells and as a result additional antigen-specific skin-homing T cells are recruited (TCR and T cells)
Describe the appearance/morphology of pigmentation/melanocytes - Freckles
1-3 mm
tan-red
Morphology
- increased pigmentation of basal keratinocytes
- slightly enlarged
Describe the appearance/morphology of pigmentation/melanocytes - Lentigo
common
benign localised hyperplasia of melanocytes
Morphology
- linear melanocyte hyperplasia above basement membrane
Describe the appearance/morphology of pigmentation/melanocytes - Melanocyte Nevus (Mole)
<6mm
Flat to elevated/round
junction + compound
Morphology
- junctional
— aggregates/nest of cells along epi/der boarder
— nuclei rounded
Compound
- nests into dermis
- epidermal nest can dissipate
- more raised than juncitonal
Junctional -> Compound = MATURATION
- deeping of roots, loss of pigment, low tyrosinase, high cholinesterase activity
- deep maturation - deep neutral like cells - melanoma from benign
- possible transformation of nevi - melanoma
Explain the maturation of non-dysplastic nevi
A - Normal skin - scattered dendritic melanocytes within epi basal cell layer
B - Junctional nevus
C - Compound nevus
D - Dermal nevus
E - dermal nevus with neurotization (extreme maturation)
Describe the pathogensis of pigmentation / melanocytes
nevi = neoplasms
- acquire mutations BRAF, NRAS
- BRAF encode kinases increase RAS signalling
- Mutation = constitutive activation of RAS/BRAF signalling
- BRAF/RAS activation increases proliferation
- Followed by growth arrest accumulation of p16/INK4a via CDKI
- Arrest disrupted in melanoma
Describe the Dysplastic Nevi - morphology/pathogenesis
Dysplastic nevi are precursors to melanoma
Most dysplastic nevi ≠ melanoma
Nevi = risk factor for melanoma
~5mm diameter
Flat, raised, dark centre
Morphology
- enlarged + can fuse together
- nevus cells replace basal membrane epi/dermis (hyperplasia)
- enlarged nucleus /irregular contours - hyperchromatic
- release of melanin - dermis - macrophage/lymphocyte recruitment - fibrosis around nevus border
Pathogenesis
- development nevi - melanoma stepwise process
— mutations, epigenetic changes
—— CDKN2A, CKD4 +NRAS + BRAF
Development stages:::
A. Lentiginous melanocytic hyperplasia
B. Lentiginous junctional nevus
C. Lentiginous compound nevus with abnormal architecture and cytologic features (dysplastic nevus)
D. Early melanoma/ in radial growth phase
Advanced melanoma (vertical growth phase) with malignant spread into the dermis and vessels
How common is melanoma?
10,300 cases diagnosed
1,430 deaths since 2008
deadly if not caught early
Describe the clinical features of Melanoma
Asymptomatic
- itching / pain
- ABCDE - asymmetry, irregular boarder, uneven colour, diameter, evolving
Describe the morphology of melanoma
Radial growth - no metastasis
- lentigo maligna
- superficial spreading
Shift to vertical growth
- deep dermal infiltration
- nodule appearance
- metastatic potential
What are prognostic factors of melanoma?
Use these
- Breslow thickness
- number of mitoses
- evidence of regression
- presence of tumour infiltrating lymphocytes
- gender
- location
Favourable
- <1.7mm
- very few mitoses
- absense of regression
- Fast TIL
Describe the pathogenesis of Melanoma
○ Inherited factors + sun exposure
§ Upper back - men & Legs - women -> light skin
§ Predisposing factor
□ 10-15% familial + dysplastic nevi
§ Mutations in RB tumour suppressor protein
□ Sporadic and familial
§ 40% CDKN2A mutation (familial)
□ Encodes tumour suppressors p14-p16
□ P16 increases RB tumour suppressor, p14 increases p53 tumour suppressor
§ Increased melanocytic proliferation, escape oncogene induced senescence
Describe Premalignant Tumours
Acitic Keratosis
- dysplastic change of epidermis -> squamous cell carcinoma
- sun damage skin + hyperkeratosis
- increased sun exposure, ionising radiation, industrial hydrocarbons
- <1cm tan-brown, red or skin colour
- rough, sandpaper
- keratinocytes accumulate
- face, arms, back of hands
Morphology
- atypical cells, deep epidermis
- basal cell hyperplasia
- hyperplastic cells have keratin staining
- superficial dermis = fibrosis
- stratum corneum thickened
- eradication
