Pigmented Skin Lesions Flashcards
Describe the formation and migration of melanocytes
Derived from the neural crest and, early in embryogenesis, MELANOBLASTS migrate from here to the skin, uveal tract and leptomeninges (melanomas can occur in the skin and eyes and, rarely, in the meninges)
Once melanoblasts settle in the skin, they form melanocytes
Where are melanocytes in the skin?
Solitary cells that are basally situated and surrounded by keratinocytes
Melanocyte : basal keratinocyte = 1 : 5 - 1 : 10
Melanocyte variation amongst different races?
Ratio is constant, irrespective of race
Describe the melanocytes in this image
Basal melanocytes have a small halo area around them and the keratinocytes adjacent are mostly pigmented
Which gene governs melanin production?
Melanocortin 1 receptor gene is central; it encodes MC1R protein (which sits on the cell surface)
Different types of melanin?
Eumelanin is responsible for hair colours other than red
Phaeomelanin is responsible for red hair
MC1R turns phaemoelanin into eumelanin
Defective copy/copies of MC1R cause?
One defective copy = freckling
Two defective copies = red hair and freckles
What are freckles?
AKA epihilides (singular is ephelis); they are patches where there is an increase in melanin pigmentation, due to UV exposure, and they are areas where there is an increase in mealnocytes
What are actinic lentigines (singular is lentigo)?
AKA solar lentigines OR age/liver spots; these are related to chronic UV exposure
Common areas with actinic lentigines?
Face, forearms, and forsal hands; there is increases melanin and basal melanocytes
Epidermis has elongated rete ridges, that extend between the dermal papillae
Development of melanocytic naevi?
AKA mole
May be CONGENITAL (1%) or ACQUIRED (majority in the 1st/2nd decade of life)
Sizes of congenital melanocytic naevi?
Small <2 cm
Medium >2 cm but <20 cm diameter
Giant-garment type lesions
Risk of melanoma with congenital melanocytic naevi?
Large lesions have a 10-15% increased risk of melanoma
Formation of usual type acquired naevi?
- During infancy, melanocytes : keratinocyte ratio breaks down at a no. of cutaneous sites
- Formation of simple naevi (very common benign lesions with most people having 20-30)
Immune regulation with relation to naevi?
Common naevi have low malignant potential; there is a question of whether naevus induction is immune regulated
Well-defined path along which acquired naevi develop?
Junctional naevus (CHILDHOOD) - melanocytes proliferate and form clusters/nests of cells at the DEJ , forming a flat mole
Compound naevus (ADOLESCENCE/early adulthood) - nests of naevus cells at the DEJ, as well as within the dermis, forming a central raised area surrounded by a flat patch
Intradermal naevus (ADULTHOOD) - naevus nests are entirely dermal, forming a papule/plaque/nodule with a pedunculated/papillomatous/ smooth surface; all junctional activity has ceased
What type of naevus is this?
Junctional naevus - there are nests of melanocytes attached to the epidermis
What type of naevus is this?
Intradermal naevus - nests of naevus cells within the dermis
Characteristics of dysplastic naevi?
>6 mm diameter
Variegated pigment
Asymmetry of the border
Resemble MM and may be difficult to distinguish from melanoma in-situ
What are the 2 clinical settings in which a dysplastic naevus can present?
SPORADIC:
Not inherited
One to several atypical naevi
Risk of MM is slightly increased
FAMILIAL:
Strong FH of melanoma and autosomal inheritance with a high penetrance
Lifetime risk of melanoma is 100%
Histological appearance of a dysplastic naevus?
Architectural and cellular atypia; the host reaction causes inflammation and fibrosis
However, unlike in melanoma, the epidermis is not effaced (junctional naevus or, more frequently, a compound naevus)
Describe halo naevi (rare)
Have a peripheral halo of depigmentation around them; these are areas of inflammatory regression that have been invaded by lymphocytes
Describe blue naevi (rare)
Entirely dermal (deeper than normal moles) and consist of pigment-rich dendritic spindle cells; cellular variant may have mitoses and mimic melanoma
Describe Spitz naevi (rare)
Benign naevi that may resemble MM (Spitzoid melanoma); they tend to occur on the faces/limbs of children
Histology of Spitz naevi?
Consist of large spindle and/or epithelioid cells
There is EPIDERMAL HYPERPLASIA
Macroscopic appearance of Spitz naevi?
Pink colouration, due to prominent vasculature; look like a haemangioma
Development of MM?
Most arise “de novo” but some arise in dysplastic naevi
Occurrence of MM?
More common in females (2 : 1) and are rare in childhood; incidence peaks at middle-age
May arise at any site
Common MM sites?
Sun-exposed sites, e.g: scalp, face, neck, arm, trunk and legs
Why do MMs sometimes occur in rare sites, e.g: anus, biliary tract, meninges, oesophagus?
Become stuck in these regions during the embryonic migration
Red flags of an MM?
Change in shape
Irregular pigmentation
Bleeding
Development of satellite nodules (bad prognostic factor)
Ulceration (bad prognostic factor)
New pigmented lesions develop in adulthood
Four main types of melanoma?
Superficial spreading (most common) - often affecting trunk and limbs and show regressed areas
Acral/mucosal lentiginous - acral, e.g: on the heel or sunungual, and mucosal
Lentigo maligna - affect sun-damaged face/neck/scalp
Nodular - affect various sites but most common on the trunk
What is meant by: RGP (radial growth phase) VGP (vertical growth phase) ?
RGP - grow as macules when either entirely in-situ or with dermal microinvasion
VGP - eventually, melanoma cells invade the dermis, forming an expansile mass with mitoses
Melanomas in which growth phase can metastasise?
Only those in VGP
What is a melanoma in-situ?
Confined to the epidermis, above the basement membrane; when they drop out, this is when they are invasive
What is nodular melanoma?
MM cells proliferate downwards through the skin – AKA vertical growth (there is no clinical/microscopic RGP and so it may be more aggressive)
Lesion presents as a nodule that has been rapidly enlarging
3 types of MM with RGP +/- VGP?
- Superficial spreading melanoma (SSM)
- Acral / mucosal lentiginous melanoma (A/MLM)
- Lentigo maligna melanoma (LMM)
MM with VGP only?
Nodular melanoma
Note: some melanomas cannot be accurately classified
What is the Breslow thickness?
mm between the deepest tumour cell and the granular layer of the epidermis
Stages of melanoma corresponding to different Breslow thicknesses?
pTis-melanoma (in-situ) - 100% survival
pT1-tumour 4mm thick - 20% survival
pT2-tumour is 1-2mm - 80% survival
pT3-tumour is 2-4mm - 55% survival
pT4-tumour > 4mm thick - 20% survival
Description of ulcerated melanomas?
Suffix “b” indicated tumour ulceration, e.g: pT3b is a tumour between 2-4 mm with ulceration but this is equivalent to a non-ulcerated pT4
Adverse prognostic factors for MM?
High mitotic rate
Lymphovascular invasion
Satellites
Sentinel lymph node involvement
Spread of MM?
- Local dermal lymphatics - satellite deposits of MM
- Regional lymph node metastases – common pattern of disease progression; nodes can have a sentinel node biopsy and be excised (radical lymphadenectomy)
- Blood spread to various bodily regions
MM treatment?
Primary excision to give clear margins
Some also receive a sentinel node biopsy and, if +ve, a regional lymphadenectomy (controversial)
Chemo/immunotherapies Genetic therapies
Excision of MM based on Breslow thickness?
If in-situ then clear by circa 5 mm
If invasive but 1 mm thick - 2cm clearance
SNB if >1 mm thick or thinner with mitoses
Mutations in different types of melanoma and how these can be specifically treated?
Some acral melanoma have c-kit mutations (treat with imatinib)
On intermittently sun-exposed skin, may have a BRAF mutation
Difference between wild Type B-Raf and mutated B-raf?
Wild type is a weak proto-oncogene; when mutated, it drives cell proliferation by up-regulating MEK and ERK
Drugs that interfere with BRAF, MEK and ERK?
Dabrafenib and Vemurafenib
Stop having an effect after 6 month and should be combined with MEK inhibitor
