Pigmented Skin lesions - PATHOLOGY Flashcards
Where do melanocytes derive from?
The Neural crest
Melanocyte - embryonic origins
Early in embryogenesis MELANOBLASTS migrate from neural crest to…
- the skin
- uveal tract
- leptomeninges
What happens once melanoblasts settle in the skin?
Form melanocytes
Basally situated
Melanocyte ratio: basal keratinocyte is constant irrespective of race
Under a microscope, what do melanocytes look like?
Dark cells with pale “halos”
MC1R genetics
Melanocortin 1 receptor gene is central
Encodes MC1R protein - sits on cell surface
Determines balance of pigment in skin and hair
Eumelanin hair colour other than red
Phaeomelanin causes red hair
MC1R turns phaeomelanin into eumelanin
One defective copy of MC1R causes freckling
Two defective copies - red hair and freckles
Ephilides
Freckles. (ephilis)
Patchy increase in melanin pigmentation
Occurs after UV exposure
Most common in fair skinned and red heads
Reflects clumpy distribution of melanocytes
Islands with most melanocytes tan
Pale intervening skin has fewer melanocytes
Have one defective copy of MC1R gene
Actinic lentigines
Actinic/solar lentigines (lentigo sg)
Age/liver spots
Related to UV exposure
Epidermis has elongated rete ridges.
Increase melanin and basal melanocytes
Melanocytic naevi
> Broad range of lesions
> May be congenital or acquired
> most naevi acquired in 1st 2 decades
Congenital melanocytic naevi
Small < 2cm diameter
Medium >2cm but < 20cm
LARGE > 20cm
Giant - garment type lesions
Large lesions have a 10-15% risk of melanoma
Acquired naevi
During infancy the melanocytes: keratinocyte ratio breaks down at a number of cutaneous sites
–>
Formation of SIMPLE NAEVI
- common benign lesions
- average person has 20-30 naevi
- low malignant potential
Type of naevus present in childhood?
Junctional naevus.
Melanocytes proliferate –> clusters of cells at DEJ
Type of naevus present in adolescence?
Compound naevus.
Junctional clusters/nests + groups of cells in dermis
Type of naevus present in Adulthood
Intradermal naevus
- all junctional activity has ceased; entirely dermal
Become flattened, become like nerves
Dysplastic naevi
> size
colour
symmetry
over 6mm diameter
Variegated pigment
Asymmetry of border
Dysplastic naevi - 2 clinical settings
Sporadic
- not inherited
- one to several atypical naevi
- risk of malignant melanoma slightly raised.
Familial
- strong FH of melanoma
- autosomal inheritance
- high penetrance
- atypical naevi
- lifetime risk of melanoma 100%
Dysplastic naevi vs melanoma
Architectural atypic and cellular atypic
Host reaction - fibrosis and inflammation
Unlike melanoma epidermis is not effaced
Severe dysplasia may be difficult to distinguish from melanoma in situ
Halo naevi
Rarer
Peripheral halo of depigmentation.
Overrun by lymphocytes
Blue naevi
Entirely dermal
Pigment rich dendritic spindle cells
Spitz naevus
Consist of large spindle &/or epithelioid cells
May mimic melanoma
Mostly benign
Can be malignant
Often pink/red because they are well vascularised
When to suspect melanoma
> Change in shape > Irregular pigmentation > Bleeding > Development of satellite nodules > ulceration > New pigmented lesion develops in adulthood
Types of malignant melanoma
Four types
> Superficial spreading - trunks and limbs
> Acral/mucosal lentiginous - acral and mucosal
> Lentigo maligna - sun damaged face/neck/scalp
> Nodular - often trunk
Acral/mucosal lentiginous
Type of malignant melanoma
Acral (toes and fingers) and mucosal
Lentigo maligna
Sun damaged face/neck/scalp
Type of melanoma
Superficial spreading melanoma; acral/mucosal lentiginous melanoma; lentigo maligna
Growing pattern
Grow as macule when either entirely in-situ or with dermal microinvasion - radial growth phase
Eventually melanoma cels invade the dermis
–> expansile mass with mitoses (VERTICAL GROWTH PHASE)
Which melanomas can metastasise?
Only Vertical growth phase melanomas
Nodular melanoma
> No clinical or microscopic evidence of RGP
> Simply a nodule of VERTICAL GROWTH PHASE tumour (no macule present)
> Considered more aggressive
Melanoma prognosis
Relates to Breslow depth and ulceration
pTis - in situ (100%)
pT1-tumour <1mm
pT2 tumour 1-2mm
pT3 is 2-4mm
pT4 >4mm thick (20%)
ULCERATION is a strong adverse indicator
Suffic “b” indicates tumour ulceration
High mitotic rate, lymphovascular invasion, satellites, sentinel lymph node involvement
Definition of Breslow thickness?
Deepest tumour from granular layer mm
Malignant melanoma - spread
- Local dermal lymphatics –> satellite deposits of MM
2. Regional lymph node metastases - common pattern Nodes excised (radical lymphadenectomy)
- Blood spread
- -> Skin/soft tissue
- -> heart
- -> lungs
- -> GI tract
- -> Liver
- -> Brain
Melanoma treatment
> Primary excision to give clear margins
> Sentinel node biopsy
- if positive then regional lymphadenectomy
> Treatment of advanced disease is difficult
If cancer is in situ, how much is cleared?
5mm ish
If cancer is invasive by <1mm thick - how much clearance?
1cm
If invasive and >1mm thick -clearance?
2cm
Sentinel node biopsy if…
> 1mm thick or thinner with mitoses
Ckit mutations treated with
Imatinib
BRAF
Weak cytosolic proto-oncogene
Mutated: drives cell proliferation by up-regulating MEK and ERK
Dabrafenib
Vemurafenib
+ MEK inhibitor
Benign seborrhoeic keratosis
Epidermal tumour
Look stuck on - rice crispy on the skin. Greasy hyperkeratotic surface
Benign proliferation of epidermal keratinocytes
Face & trunk
Epidermal acanthosis, hyperkeratosis, horn cysts
Precancerous dysplasias
Bowen’s disease
Actinic keratosis
Viral lesions
Invasive malignancies
Basal and squamous cell carcinoma
Epidermal acanthosis
Thickening
Eruptive appearance may indicate…
Internal malignancy
Leser-Trelat sign
Leser-Trelat sign
the explosive onset of multiple seborrheic keratoses (many pigmented skin lesions) often with an inflammatory base.
BCC subtypes
- Nodular
- Superficial
- Infiltrative (morphoeic)
Where do BCCs sprout from?
From epidermis.
Groups of cells invade the dermis.
Peripheral palisading.
Mitoses and apoptosis very numerous
Are BCCs slow or fast growing?
Slow growing
Locally destructive
Almost never metastasises
Could invade eye –> brain
Most important type of BCC?
Infiltrative.
May infiltrate tissues widely.
Prominent desmoplastic fibrous stroma
Margins are poorly defined
May spread along nerves
Resection may be challenging.
Precursors of SCC
Range of precursors for SCC
Bowen’s disease - especially on legs
Actinic keratosis - esp head and neck
Viral lesions - especially on anogenital skin
Precursors show squamous DYSPLASIA
Precursors of SCC show?
Dysplasia
BOWEN’S DISEASE
SCC in situ
Mostly on lower leg
Scaly patch/plaque
Irregular border
No dermal invasion.
Actinic keratosis
Common
Sun exposed skin
Variable epidermal dysplasia
Common precursor of invasive SCC
Viral precursors
> Viral genital lesions often dysplastic
> Erythroplasia of Queryat- Bowen’s of glans
> Associated with HPV
HPV Type 16 associated with…
Dysplasia
HPV in 100% of
Penile dysplasia
HPV found in 50% of
Invasive penile SCC
Most common clinical setting for SCC
Elderly, sun exposed sites
UV implicated
Occasional setting for SCC
Rare
> Chronic leg ulcers
Sites of burns
Chronic lupus vulgaris
Rare - xeroderma pigmentosum (dystrophic varian of epidermolysis bullosa)
Xeroderma pigmentosum
Cant repair the DNA
Accumulate mutations very quickly and develop numerous skin tumours.
SCC
> Behaviour
Adverse Prognostic features
BEHAVIOUR:
> generally good prognosis
> locally invasive
> low but definite risk of metastasis
ADVERSE PROGNOSTIC FEATURES
- Thickness > 4mm and poor differentiation
- lymphatic / vascular space invasion
- perineural spread
- specific sites poorer prognosis - scalp, ear, nose
Columella
columella is the bridge of tissue that separates the nostrils at the nasal base
1.Dermatofibroma
Dermatofibrosarcoma protuberans
- overgrowth of the fibrous tissue situated in the dermis
2. very rare tumor. It is a rare neoplasm of the dermis layer of the skin,[2] and is classified as a sarcoma.
Angiosarcoma
diffuse
Bruise-like lesion
Highly malignant
Merkel cell carcinoma
HIGHLY AGGRESSIVE SKIN CANCER
Pressure receptor cells beneath the basement membrane
Cutaneous equivalent of small cell carcinoma of lung
Merkel cell polyomavirus
(Primary small cell neuroendocrine)
Mycosis fungoides
Cutaneous T cell lymphoma
T cells move towards epidermis
Neoplastic T cells
Epidermotropic
Cutaneous B cell lymphoma
Tumours of the lymph nodes and lymphatic system
Malignant proliferation of B cell lymphocytes
