Skin Flashcards
1
Q
Where can skin cancers arise?
A
MECA O
- Epidermis
- Connective Tissue
- Melanocytes
- Adnexae
- Other Components
2
Q
Skin tumours of the epidermis
A
Seborrhoeic keratosis*
Keratocanthoma
Basal cell carcinoma*
Squamous carcinoma*
3
Q
Skin tumours of the connective tissue
A
Dermatofibroma DFSP (Dermatofibrosarcoma) Haemangioma Leiomyoma/Sarcoma Angiosarcoma Kaposi’s sarcoma
4
Q
Skin tumours of melanocytes
A
Melanocytic naevi*
Melanoma*
5
Q
Skin tumours of adnexae
A
Hair follicle
Sweat gland
Sebaceous gland
6
Q
Benign epidermal tumours
A
◦ Seborrhoeic keratosis/wart
◦ Viral wart (HVP)
◦ Keratoacanthoma
7
Q
Malignant epidermal tumours
A
◦ Basal cell carcinoma
◦ Squamous carcinoma
8
Q
What’s a seborrhoeic keratosis/wart
A
Syn. Basal cell papilloma
◦ Very common - middle-old age
◦ Greasy, warty plaques
◦ Uniform small-medium sized basaloid cells
9
Q
Basal cell carcinoma
A
Terminology: BASAL CELL: Cells resemble epidermal basal cells CARCINOMA: Malignant tumour Commonest malignant tumour BCC:SCC = 4:1 Not a truly epidermal tumour ◦ related to hair follicle epithelium
10
Q
What’s the commonest malignant skin tumour?
A
BCC
11
Q
What causes ageing and skin wrinkling?
A
UVA
12
Q
Basal Cell Carcinoma: Risk factors
A
UVB- intermittent exposure
Skin type -pale skin, red/blond hair, freckles etc
(The lower the skin type the higher the risk)
Genetic conditions:
Gorlin’s syndrome –PTCH-1 gene mutation
Xeroderma pigmentosum (of nucleotide excision repair)
Immunosuppression
Others – e.g. radiation
13
Q
Basal Cell Carcinoma: Clinical
A
“Rodent ulcer” as it eats through structures
Sun-exposed sites (UVB)
Middle-old age (cumulative sun exposure)
“pearly nodule with telangiectasia” But also plaques, ulcers (depends on growth pattern)
Slow growing
Small (Usually <2cm but occ. much larger)
Behaviour:
10% recur (Depends on growth pattern and resection margins)
1:10,000 - 1:50,000 metastasise (HARDLY EVER)
14
Q
Prognostic factors of BCC
A
Diameter of lesion
Site (head and neck worse)
Tumour type (pattern- infiltrative and micronodular are more likely to recur)
15
Q
What does squamous carcinoma look like?
A
Squamous cell: Tumour cells resemble the keratinocytes of then epidermis
Often show keratinisation like the stratum corneum of the epidermis
16
Q
Is squamous carcinoma malignant?
A
Yes but... Terminology confusing as it may be ◦ Invasive (truly malignant) ◦ In-situ (premalignant): Solar/actinic keratosis Bowen’s disease
17
Q
Squamous Carcinoma: Risk factors
A
UVB (cumulative exposure, p53 mutations) Skin type Immunosuppression (more so than BCC) HPV (as in uterine cervix) Genetic conditions e.g. XP Others e.g. scars, chronic ulcers,etc
18
Q
What’s actinic keratosis?
A
Scaly papules/small patches on sundamaged skin (UVB)
Common in elderly pale-skinned individuals
19
Q
Histology of actinic keratosis and what can it become?
A
Histo:
- Variable dysplasia (akin to CIN of cervix)
- Only severe dysplasia = in situ scc
Evolution of lesions
- development of invasive scc
20
Q
What’s Bowen’s disease?
A
Type of squamous carcinoma in situ
Middle - old age
Large red-brown scaly (“flaky”- keratin ) patches
More common in sun-exposed skin
Severe dysplasia
21
Q
Pathology of squamous cell carcinoma
A
◦ Malignant squamous cells
Keratinised frequently
Pink
◦ Infiltrate the dermis/subcutis
◦ Variable degrees of differentiation (grade)
Well, moderate, poor
Depending on how much the cells resemble normal epidermal cells
22
Q
Behaviour of squamous cell carcinoma
A
◦ Locally destructive
◦ More likely to metastasise than bcc
Local lymph nodes
Lungs, etc
◦ Less than 5% metastasise BUT depends on site, grade and thickness of tumour
◦ Stage of tumour depends on how early it is discovered (and how thick it is)
23
Q
Poor prognostic features for squamous carcinoma
A
Sites with poor prognosis: ◦ Lips- at least 15% metastasise ◦ Ears - about 10% metastasise ◦ Vulva ◦ Anus
Histological features:
◦ Tumour thickness
◦ Tumour grade
◦ Completeness of excision
Immunosuppression
24
Q
How is Keratoacanthoma similar and different to SCC?
A
Common features with SCC:
Sun-exposed skin
Nodule with keratin BUT within a central crater
Histo: Well differentiated SCC BUT central crater
Differentiating features fromSCC:
Grows quickly (weeks) and spontaneously regresses (months)
Does not recur or metastasise
25
Stages of progression of melanocytic tumours
```
1.Benign
◦ Melanocytic naevi:
- Common acquired (usual “run of the mill”)
- Congenital
- Special naevi: Blue, Spitz, etc
```
2. Dysplastic (premalignant)
◦ Dysplastic naevi
3.Malignant
◦ Melanoma
26
Moles aka
melanocytic naevi
| sometimes look blue if the melanin is deep in the skin
27
Features of melanocytic naevus
Initial presentation:10 and 25 years old
Variable numbers (some families and skin types more prone)
Natural evolution:
- Usually arise at epidermal-dermal junction
(junctional)
- Evolve over many years with nests of melanocytes
entering the dermis (compound)
- Eventually become totally intradermal (intradermal)
Very few may become malignant
28
Melanoma: Risk factors
UVB
◦ Intermittent exposure (“ordinary” melanoma)- burning episodes in childhood
◦ Chronic exposure in some – lentigo maligna on face
◦ NOT in acral or nail melanoma
Skin type
Family history - familial melanoma/dysplastic naevus syndrome
Multiple benign naevi
Congenital naevi - “giant
29
Clinical signs of melanoma
(ABCD)
Brown/blue/black pigmentation
◦ melanin, depends on its location within the skin
Macules, patches (generally if in situ), papules and nodules (generally if invasive)
Bigger, more irregularly shaped and pigmented
than benign naevi
Changes in previously stable naevus
Itching and bleeding
30
Directions of melanoma growth
Large, pleomorphic melanocytes arranged singly, in nests and large nodules
Majority grow for a prolonged period in the epidermis
+/-superficial dermis - RADIAL GROWTH PHASE
Later develop capacity for deeper invasion/metastatic spread = VERTICAL GROWTH PHASE
31
Melanoma prognosis
```
Age - worse with increasing age
Sex - women better than men
Site - arms and legs better than other sites
STAGE - localised > LN > systemic
BRAF mutations do better due to better therapy
TUMOUR THICKNESS
◦ <1mm = 99% (pT1)
◦ >4.00mm = <40%
Mitotic count (pT1a vs pT1b)
Presence of ulceration
Level of invasion (Clark)
Host lymphocyte response and regression
```
32
Treatment of melanoma
Primary excision
Re-excision
Sentinel lymph node bx (pT1b and above)
Lymphadenectomy
Medical treatment
◦ BRAF mutant- “nibs”- Signalling inhibitors that stop cell cycle
◦ BRAF wild type- “mabs”- Immunotherapy that activates immune system
33
Basal cell carcinoma main points
Slow growing
Locally destructive
Local recurrence
Virtually never metastases
34
Squamous cell carcinoma main points
Variable growth rate
Locally destructive
Local recurrence
Metastases much commoner
35
Sometimes melanomas contain large areas that are non-pigmented. What are these called and how do they arise?
amelanotic. In these areas the malignant melanocytes have lost the capacity to produce melanin pigment.
36
What are the clinical features which might help distinguish a melanoma from a benign naevus?
'ABCD'
'A' stands for asymmetry. Melanoma is often asymmetrical whereas benign naevi should show a uniform symmetrical appearance.
'B' stands for borders. In melanoma the border of the lesion is often ill defined or irregular.
'C' stands for colour. In melanomas it is not unusual to see different shades of colouring ranging from red to brown, black and even grey. The more colourful a pigmented skin lesion the more suspicious it is of malignancy.
'D' stands for diameter, i.e. size (>6 mm).
Other pointers are: new pigmented lesion, change of pigmentation or growth in a pre-existing naevus, itching or bleeding. If in doubt, a pigmented lesion should be excised and the majority of melanomas are cured by early surgical excision.
37
Risk factors for melanoma
ultraviolet radiation (UVB
- intermittent (i.e. burning episodes, particularly in childhood)
- chronic (cumulative)
There is some evidence now that the genetic abnormalities vary between melanomas occurring on chronically sun-exposed sites (C-kit) and those occurring on intermittently sun-exposed sites (NRAS and BRAF). This is increasingly important because of targeted chemotherapy for metastatic melanomas.
Skin type (pale freckled skin, red / blond hair) is also an important risk factor. Others are family history (dysplastic naevus syndrome), multiple benign naevi and large congenital naevi.
38
How would you explain the findings? In the dermis and subcutaneous tissue there is a well circumscribed darkly pigmented nodule. The overlying skin surface shows no obvious pigment.
The absence of surface involvement suggests that this is most likely a metastatic melanoma deposit. In fact, the skin / subcutis between a primary melanoma and local lymph nodes is a common site of metastasis (so-called in-transit metastasis). Melanoma may recur locally, spread via the lymph nodes and systemically via the blood stream most commonly to liver, lung, brain and skin. It may recur many years after removal of the primary melanoma.
39
What is the most important prognostic factor for melanomas?
The most important prognostic factor is the thickness of the lesion at the time of primary excision. It is called the Breslow thickness and is measured in mm. The presence or absence of surface ulceration is also important. The cure rate for completely excised non-ulcerated melanomas <1mm approaches 100%, whereas the 5-year survival for lesions >4mm is < 40%. Clearly, increasing age, site (arms and legs are better than other sites) and overall stage (localised > lymph node metastasis > systemic metastasis ) also play a role.
40
How do nodular melanoma grow?
Nodular melanoma invade rapidly without a discernible radial growth phase.
41
What are the most common sites for nodular melanoma?
trunk, head and neck
It is more common for nodular melanoma to begin in normal skin rather than in a pre-existing lesion.
42
What's the tumour?
On the head, ulcerated lesion with rolled everted edges, tumour does not appear to reach the deep margin formed by the aponeurosis
BCC
43
What's the tumour?
On the skin, pearly papules or nodules +/- ulceration.
BCC
44
Nests of darkly staining atypical cells invade the dermis but do not invade the subcutaneous fat. The nests show peripheral palisading (cells lined up like a fence around the edge of the nests) which is characteristic of....
basal cell carcinoma
45
Surface crusting suggestive of...
keratinisation and the most likely diagnosis is that of a squamous cell carcinoma (SCC)
46
Which malignant epidermal tumour are you more at risk of if you're immunosuppressed?
SCC
47
What are the precursor lesions of squamous cell carcinoma in the skin?
Invasive carcinoma of the skin often develops from premalignant dysplastic epithelium following sun-damage. These lesions are termed actinic or solar keratoses. Severely dysplastic lesions are termed squamous carcinoma in-situ or Bowen's disease.
48
What is a keratoacanthoma and how does it differ from squamous cell carcinoma?
Keratoacanthoma is a rather curious lesion which may mimic squamous cell carcinoma. However, clinically it is a benign lesion and it regresses. It is characterised by a symmetrical crater-like appearance, often occurs on sun-damaged skin, grows very rapidly for several months and then regresses. Histologically, it is virtually indistinguishable from a well differentiated squamous cell carcinoma. However, it never invades deeply and does not metastasise. The architectural symmetry may not be appreciated unless the lesion is excised intact rather than curetted. This tumour may represent a special form of squamous cell carcinoma, which is clinically benign because of its ability to totally regress.
49
Histology of SCC
- squamous eddies
- keratin pearls
- some cells stain deeply pink because of the keratinisation
- intercellular bridges (or prickles)
50
What are cutaneous horns and what are they made of?
A conical projection above the surface of the skin which resembles a miniature horn. It is composed of compacted keratin similar to that of the very superficial layers of the epidermis.
51
What does curetted off mean?
Scrape off
52
What should you do if you take a horn off?
Examine the underlying epithelial lesion!
Whilst the majority are benign (e.g. seborrhoeic keratosis or benign wart), the lesion may be composed of dysplastic epithelium (actinic keratosis) or harvest squamous cell carcinoma in-situ (Bowen's disease).
Even an invasive squamous cell carcinoma may be found. Therefore, the presence of a cutaneous horn is a clinical diagnosis and the underlying keratinising lesion may be of a benign, dysplastic or malignant nature.
53
Common cause of tense bullae in elderly, symmetrical on thighs, forearms, axillae, groin, and abdomen. Oral involvement 30%
Bullous pemphigoid
54
Type II hypersensitivity.
| Antibodies develop against BPAg1or BPAg2 in hemidesmosomes of basement membrane.
Bullous pemphigoid
55
Inflammation with many eosinophils in blister.
Bullous pemphigoid
56
Deposition of IgG antibody & complement C3 along basement membrane zone seen in immunofluorescence.
Bullous pemphigoid
57
Treatment of bullous pemphigoid
```
Corticosteroids
Immunosuppressive drugs (azathioprine, methotrexate)
```
58
Spongiotic rash on the flexor surfaces of skin (antecubital and popliteal fossae, posterior neck, wrist, hands, ankels, feet)
Atopic dermatitis in adults
59
Spongiotic rash on the face, scalp and extensor surfaces of skin
Atopic dermatitis in infants
60
Classification of eczema (to boil out)
Endogenous (hereditary)
- Atopic dermatitis
- Seborrhoeic dermatitis
- Discoid (nummular) eczema
- Pompholyx
Exogenous (environmental)
- Allergic contact
- Irritant contact
61
Eczema, male predominance with two peaks (infancy and adults)
Seborrhoeic dermatitis
62
Areas affected by seborrhoeic dermatitis
Scalp, forehead, cheeks, presternal and interscapular areas
63
- Single or multiple coin shaped erythematous lesions covered in fine scale
- mostly young women
Discoid eczema
64
Areas affected by discoid eczema
Lower legs, forearms and back of hands
65
Symmetrical intensely itchy vesicles on the palm and sides of fingers, history of atopy
Pompholyx
66
Dermititis caused by type IV hypersensitivity. Antigens processed by Langerhans cells and presented to naïve CD4 T cells in lymph node.
Re-exposure caused T cell release of cytokines.
Allergic contact dermatitis
67
Test for type IV sensitivity
Patch test
68
Treatment for eczema
Emollients (aqueous cream, paraffin)
Steroids (hydrocortisone)
Immunosuppressants (azathioprine)
69
Rubbing of skin produces erythema and edema
Darier sign
70
Itchy grouped vesicles present on the extensor surfaces, elbows, knees, upper back and buttock. Associated with celiac disease.
Dermatitis herpetiformis
71
Treatment for dermatitis herpetiformis
dapsone and avoid gluten
72
Subepidermal blisters filled with neutrophils form at tips of dermal papillae. Direct immunofluorescence shows granular deposits of IgA at the tips of the dermal papillae.
Dermatitis herpetiformis
73
Localized cutaneous form of lupus. Usually does not develop systemic disease (SLE).
Discoid lupus erythematosus
74
Chronic, relapsing and remitting
| Adults 20-30, 50-60
Psoriasis
75
Scalp extensor surfaces, lower back, umbilicus and genitals
Psoriasis
76
Sharply demarcated erythematous plaques, silvery scaly surface, multiple and symmetric
Psoriasis
77
Bleeding when scale is removed
Auspitz's sign
78
Pathogenesis of psoriasis
T- cell mediated
| An increased proliferative rate of keratinocytes stimulated by IFN-gamma
79
Triggers of psoriasis
```
Infection
Stress
Withdrawal of steroids
Drugs
Trauma
```
80
Normal vs psoriatic transit time of keratinocytes from the basal cell layer to the stratum corneum
56 days
7 days
81
Thickened stratum corneum with confluent parakeratosis.
| Regular hyperplasia of the epidermis with elongation of the rete pegs and thinning of the suprapapillary plate
Psoriasis
82
What is parakeratosis?
Retained nuclei in the keratin layer
83
Targetoid lesions caused by hypersensitivity response to HSV, Mycoplasma, sulfa, penicillin, barbiturates, carcinogens, lupus erythematosus, and dermatomyositis.
Erythema multiforme
84
Histology shows dyskeratotic keratinocytes, vacuoles in basal layer, and lymphocytes chewing up dermal-epidermal junction.
Erythema multiforme
85
Target lesions on hands, mucosal involvement, can get full thickness apoptosis
Erytema multiforme
86
Severe urticaria-like swelling of face and airways caused by C1 esterase inhibitor deficiency, which leads to uncontrolled complement activation.
Hereditary angioedema
87
Pruritic, Purple, Polygonal Papules & Plaques on skin and mucosa. May be associated with HepC. May involve gingival, buccal, or vulvar mucosa.
Histology shows hyperkeratosis, hypergranulosis, “sawtoothing” at DE junction, and Apoptotic dying keratinocytes (Civatte body). Dense band of lymphocytes at DE junction.
Lichen Planus
88
Thin papery itchy skin, often genital area. Risk of squamous cell carcinoma.
Lichen sclerosus
89
Chronic eczema, epidermis becomes hyperplastic and the stratum corneum is thickened
Lichenification
90
Treatment of psoriasis
Topical treatments (tar and steroids)
PUVA
Immunomodulators and suppressants
91
Autoantibodies to desmoglein 1 & 3
Pemphigus vulgaris
92
Flaccid blisters that rupture easily resulting in shallow erosions with crust in the middle aged and elderly. Oral mucosal involvement.
Pemphigus vulgaris
93
IgG autoantibodies against desmosomal proteins leads to loss of intercellular attachments within epidermis. Type II hypersensitivity reaction.
Pemphigus vulgaris
94
Suprabasilar blister (split above basal cell layer) that leaves “tombstone row” of basal layer. “Fish net” appearance on immunofluorescence staining. Treat with corticosteroids.
Pemphigus vulgaris
95
Sites affected by pemphigus vulgaris
Scalp, face, axillae, groins but can be generalised
| Aslo oesophagus and conjunctiva
96
What's acantholysis?
The loss of intercellular connections, such as desmosomes, resulting in loss of cohesion between keratinocytes, seen in diseases such as pemphigus vulgaris. The cells can float in the blister.
97
Well-demarcated pink plaque covered with loose silvery scales on elbows, knee, scalp, lumbosacral area, intergluteal cleft and glans penis. Oilslick nail discoloration and pitting.
Psoriasis
98
Associated with arthritis, myopathy, enteropathy, AIDS, CV diseases, and depression. T cells infiltrate the skin and secrete cytokines and growth factors that increase squamous cell turnover, vascular proliferation and inflammation. Histology shows diffuse parakeratosis, absent granular layer, elongation of rete ridges, tortuous capillaries in papillary dermis, and neutrophil microabscess in stratum corneum.
Psoriasis
99
Large, necrotic ulcers with rolled, undermined red-purple borders. May recur repeatedly for years. Associated with inflammatory bowel disease. Can be mistaken for necrotizing
fasciitis. Treat with systemic corticosteroids
Pyoderma gangrenosum
100
Assoicated with viral infection
Erythma multiforme
| Treat with acyclovir
101
Interface dermatitis
lichenoid
102
Hypersensitivity response to HSV, Mycoplasma, sulfa, penicillin, barbiturates, carcinogens, lupus erythematosus, and dermatomyositis that covers <30% of body area.
Extensive and symptomatic. Erosion and crusting of mucosal surfaces.
Steven Johnson Syndrome
103
Hypersensitivity response to HSV, Mycoplasma, sulfa, penicillin, barbiturates, carcinogens, lupus erythematosus, and dermatomyositis that covers >30% body area.
Diffuse necrosis and sloughing of cutaneous and mucosal surface. Positive Nikolsky sign. Full thickness necrosis and death of epidermis.
Toxic Epidermal Necrolysis
104
Allergy (immediate) hypersensitivity caused by antigen binding to IgE on mast cells.
Type I hypersensitivity
105
Cytotoxic, antibody-dependent hypersensitivity caused by IgM and IgG binding to antigens.
Type II hypersensitivity
106
Immune complex hypersensitivity caused by complexes of antigens and IgG antibodies.
Type III hypersensitivity
107
Delayed-type hypersensitivity, cell-mediated immune memory response, antibody-independent hypersensitivity caused by T cells recognizing antigens bound to MCH II on antigen
presenting cells.
Type IV hypersensitivity
108
Face, lips, buttocks, genitals
Round/oval lesions within 30mins-8 hours
Hyperpigmented macule in same place
Fixed drug eruption
109
commonly presents as painless, mobile, solitary mass in the elderly
lipoma
110
most common malignant neoplasm, rolled borders, peripheral palisades
basal cell carcinoma
111
shiny, white plaques on an erythematous base
psoriasis
112
the term describing the normal loss of orthokeratosisnuclei in the stratum corneum
orthokeratosis
113
scaly papules or plaques on sun-bearing skin, can progress to SCC
actinic keratosis
114
pattern describing a band of inflammatory cells at the dermal-epidermal junction
lichenoid
115
'stuck-on' papules or plaques on hairbearing skin
seborrheic keratosis
116
absence of melanocytes, resulting in depigmented patches
vitiligo
117
replacement of the spinous and granular layers by basaloid keratinocytes; squamous cell carcinoma in situ
Bowen's disease
118
CREST
calcinosis, Raynaud's phenomenon, sclerodactyly, telangectasia, esophageal dysmotility
119
firm nodules or ulcers on sun-exposed skin, nuclear pleomorphism, dyskeratosis, keratin pearls
squamous cell carcinoma
120
benign vascular proliferation, common in children
hemangioma
121
bloodborne variant of T cell lymphoma where skin becomes red all over body
sezary syndrome
122
virus that causes verruca vulgaris
HPV-2
123
melanoma in situ, common in head and neck
lentigo maligna
124
most common cause of skin cancer death
melanoma
125
pruritic, purple, polygonal, planar papules and plaques
lichen planus
