Skin Flashcards
What is the outermost layer of the epidermis
The stratum corneum.
What cell types are found in the epidermis that are relevant to cutaneous malignancies
Melanocytes
Dendritic cells (langerhans cells)
Squamous epithelial cells
Merkel cells
What is the full name for a mole. What type of mutations are common
Melanocytic nevus
RAS and BRAF mutations are common. They usually don’t go on to become malignant because they induce senescence via p16/INK4.
What type of lesion can be a direct precursor to melanoma. What are frequent mutations these contain
Dysplastic nevi.
NRAS and BRAF mutations (ie similar to melanocytic nevi), but they often also have mutations of the CDKN2A gene, so senescence is not induced
What are macroscopic and microscopic features that distinguish a melanocytic nevi from dysplastic nevi
Macroscopic: larger size, variability in pigmentation, irregular borders
Microscopic: cytological and architectural atypia
What is the most important predisposing factor for risk of melanoma
UV exposure
What are the most common driver mutations in melanoma
CDKN2A: affecting p16 and ARF production
Growth signalling pathways; BRAF (non V600E), NRAS, PTEN, KIT
NF1
Mutations activating telomerase
What receptor tyrosine kinase has frequent activating mutations in melanoma
KIT, particularly mucosal melanoma
What are the two growth phases of melanoma
Horizontal growth phase: epidermis/ superficial dermis spreading of the melanoma, with less malignant potential. This phase is the earlier phase
Vertical growth phase: deeper invasion into the deep dermis with increased malignant potential
What are the microscopic features of melanoma
Larger than normal melanocytes, enlarged nuclei with red (eosinophilic) nuclei, and chromatin clumped at periphery of nuclei.
What pathological features are used to predict probability of metastatic spread of an excised melanoma
1- depth of invasion/breslow thickness
2- number of mitosis
3- evidence of tumour regression
4- ulceration of overlying skin
5- presence and number of tumour invading lymphocytes
6- location
What is the relevance of sentinel lymph node micrometastases in melanoma
A worse prognosis. Degree of involvement prognosticates for overall survival
What are the clinical warning signs for melanoma
ABCDE
A- asymmetry
B- irregular Borders
C- variegated Colour
D- diameter
E- evolution, ie change over time
What does pembrolizumab inhibit
PD-1
What is mutated in Cowden syndrome, what is its normal role
PTEN, a suppressor of the PI3K pathway
What pre-malignant lesson of the skin is often a precursor to SqCC
Actinic keratosis
What are some microscopic features of actinic keratosis
Thinning of epidermis or hyperplasia of basal cells
Thickened elastic fibres
Thickened stratum corneum with retained nuclei (parakeratosis)
What are risk factors for developing skin SqCC
1: UV exposure/ lifetime exposure to sun
2: immunosuppression; possibly due to ability of HPV viruses to cause infection.
What mutations are common in cutaneous SqCC
P53
Also RAS and Notch signalling
What signalling pathway is mutated in most cutaneous basal cell carcinomas
The hedgehog pathway.
It becomes constitutively activated, no longer needing signalling from the sonic hedgehog (SHH) signalling molecule. This causes upregulation of growth promoting gene signalling.
What pathway is mutated in Gorlin’s syndrome. What malignancies are associated with it
Also known as nevoid basal cell carcinoma syndrome
Hedgehog pathway: mutation of PTCH1 gene which is inhibitor for pathway. Therefore pathway becomes more active
Hedgehog pathway important for normal development of cerebellum
Associated with early onset BCCs, medulloblastoma, ovarian fibromas
What are the two main neoplasms of the dermis (from primary dermis cells) benign or malignant
Benign fibrous histiocytoma (dermatofibroma)
Dermatofibrosarcoma protruberans: a low grade sarcoma that doesn’t tend to metastasise.
