Pathology

Question 1

What are the functions of the skin?

Answer 1

Barrier
Thermoregulation
Fluid and electrolyte balance
Endocrine function
Melanin pigment
Immune function
Sensory function

Question 2

Describe the papillary dermis

Answer 2

Thin, lies just beneath the epidermis

Question 3

Describe the reticular dermis

Answer 3

Thicker bundles of type 1 collagen and contains appendage structures

Question 4

Define hyperkeratosis

Answer 4

Increased thickness of the keratin layer

Question 5

Define parakeratosis

Answer 5

Persistence of nuclei in the keratin layer

Question 6

Define acanthosis

Answer 6

Increased thickness of the epithelium

Question 7

Define spongiosis

Answer 7

Oedema in the epidermis

Question 8

What are the 4 main reaction patterns for inflammatory skin disease

Answer 8

Spongiotic-intraepidermal oedema
Psoriaform elongation of the rete ridges
Lichenoid basal layer damage
Vesiculobullous blistering

Question 9

Describe the Koebner phenomenon

Answer 9

New psoriasis lesions arising at sites of trauma

Question 10

What are lichenoid disorders characterised by?

Answer 10

Damage to the basal epidermis

Question 11

Histology of lichen planus

Answer 11

Irregular sawtooth acanthosis
Band like upper dermal infiltrate of lymphocytes
Basal damage with formation of cytoid bodyes

Question 12

What is irregular sawtooth acanthosis?

Answer 12

Jagged appearance of the rete ridges of the epidermis

Question 13

What is the presentation of immunobullous disorders?

Answer 13

Vesicles and bullae occur as secondary phenomena in many skin diseases

Question 14

What happens to form bullae in pemphigus?

Answer 14

Loss of integrity of epidermal cell adhesions

Question 15

Describe the mechanism of pemphigus vulgaris

Answer 15

IgG auto-antibodies made against desmoglein 3
Desmoglein 3 maintains desmosomal attachments
Immune complexes form on the cell surface
Complement activations and protein release
Disruption of desmosomes
Acantholysis

Question 16

What happens to form bullae in bullous pemphigoid

Answer 16

Sub-epidermal blister without evidence of acantholysis

Question 17

What is dermatitis herpetiforms strongly associated with

Answer 17

Coeliac disease

Question 18

What are the hallmarks of dermatitis herpetiforms?

Answer 18

Papillary dermal micro-abcesses

Question 19

What is the mechanism of dermatitis herpetiforms?

Answer 19

Direct immunoflouresence shows deposits of IgA in the dermal papilla
Targets the gliadin component of gluten but cross react with connective tissue matrix proteins
Immune complexes form in dermal papilla and activate complement

Question 20

What is acne a disorder of?

Answer 20

The sebaceous glands

Question 21

What is the mechanism of acne?

Answer 21

Keratin plugging of pilosebaceous units

Question 22

What is the prevalence of rosacea in caucasian adults?

Answer 22

~10%

Question 23

How does rosacea present?

Answer 23

Recurrent facial flushing

Leading to eventual thickening of the skin

Question 24

What is often noted in rosacea?

Answer 24

Follicular demodex mites

Question 25

What is an oncogene?

Answer 25

An overactive form of a gene that positively regulates cell division

Question 26

What is a tumour suppressor

Answer 26

A gene that down regulates cell division

Question 27

What are the two forms of melanin and which is more efficient?

Answer 27

Eumelanin and pheomelanin | Eumelanin is more efficient

Question 28

What are the 5 types of DNA damage?

Answer 28

``` Altered or missing base Incorrect base Insertion/deletion Strand break Crosslinking ```

Question 29

What are the two major types of UVB-induced DNA lesions?

Answer 29

Cyclobutane pyrimidine dimers | Pyrimidine-pyrimidone (6-4) photo-products

Question 30

What repairs UVB induced lesions

Answer 30

DNA polymerase

Question 31

How does UVA cause damage to DNA

Answer 31

Via the oxidation of DNA bases

Question 32

Outline excision repair of DNA

Answer 32

Repair of oxidised bases 1. Recognition of chemically altered base causing slight helix distortion 2. Cleavage of altered base from the deoxy-ribose by DNA glycosylase 3. Base-free deoxyribose cleaved away endonuclease 4. Single nucleotide gap filled by DNA polymerase beta 5. DNA ligase seals the end

Question 33

How do UV rays induce immunosuppression?

Answer 33

Depletion of langerhans cells UV induced regulatory T cells with immune supressive activity Secretion of anti-inflammatory cytokines by macrophages and keratinocyes

Question 34

What mutations are important in BCC?

Answer 34

Mutations in PTCH1 | Key component of hedgehog signalling pathway

Question 35

What does hedgehog signalling do?

Answer 35

Activates transcription factors Gli 1/2, leading to induction of cell proliferation genes and angiogenesis factors

Question 36

What drug can be used in the case of mutation in PTCH1?

Answer 36

Vismodeglib

Question 37

What genes have been linked to familial melanoma?

Answer 37

CDKN2A | CDK4

Question 38

What does CDKN2A do?

Answer 38

Prevents cells from replicating when they contain damaged DNA by activating G1/S

Question 39

What does CDK4 do?

Answer 39

Permits cell cycle progression by phosphorylation of retinoblastoma protein

Question 40

What are the important mutations in melanoma?

Answer 40

Ras/Raf/MAPK signalling pathways | ~50% of melanomas have activating BRAF mutations

Question 41

Which drugs target the mutated form of BRAF?

Answer 41

Vemurafenib and dabrafenib

Question 42

Apart from verumafenib and dabrafenib what type of drugs are starting to be used in melanoma?

Answer 42

Target MEK | Trametinib

Question 43

What gene determines how pigmented we are?

Answer 43

MCR1 gene 1 defective = freckles 2 defective = freckles + red hair

Question 44

What are actinic lentigines?

Answer 44

Age or liver spots, related to UV exposure

Question 45

What are junctional naevi?

Answer 45

Melanocyte nests develop along the dermal epidermal junction

Question 46

What are compound naevi?

Answer 46

Juntional clusters and dermis involvement

Question 47

Junctional naevi, compoun naevi, and _______ naevi

Answer 47

Intradermal naevi

Question 48

What are the two clinical settings of dysplastic naevi?

Answer 48

Sporadic | Familial (lifetime MM risk 100%)

Question 49

What are the rarer naevi?

Answer 49

Halo naevi Blue naevi Spitz naevi

Question 50

Is malignant melanoma entirely dependant on UV exposure?

Answer 50

No, it is mostly dependant on UV exposure but it is multi factorial and genetics also plays a role

Question 51

What are the 4 main types of melanoma?

Answer 51

Superficial spreading Acral/mucosal letigo Letigo maligna Nodular

Question 52

What is melanoma prognosis largely related to?

Answer 52

Breslow thickness

Question 53

Define breslow thickness

Answer 53

The distance between the upper layer of the epidermis and the deepest layer of the cancer In ulcerated cancers measurement is from the base of the ulcer

Question 54

What is seborrhoeic keratosis?

Answer 54

Benign profliferation of the epidermal keratinocytes

Question 55

What are the 3 main types of basal cell carcinoma?

Answer 55

Nodular Superficial Infiltrative

Question 56

How are BCCs described?

Answer 56

Slow growing Locally destructive Poorly defined margins

Question 57

What is Bowen's disease?

Answer 57

A precursor of SCC | Scaly patch, irregular border, no dermal invasion

Question 58

What is actinic keratosis?

Answer 58

A precursor of SCC Sun exposed skin several atypical bowenoid lesions

Question 59

Where do SCCs occasionally arise?

Answer 59

Chronic leg ulcers | Sites of burn

Question 60

Adverse prognostic features of SCC

Answer 60

>4mm Vessel invation Perineural spread