Pathology of Pigmented Lesions Flashcards
What components of the skin can give rise to tumours?
All of them = epidermis, dermis, melanocytes, appendages, lymphoid elements
Where are melanocytes derived from?
The neural crest
How are melanocytes formed?
Early in embryogenesis melanoblasts migrate from the neural crest to the skin, uveal tract and leptomeninges, once melanoblasts settle in the skin they from melanocytes
Where are the melanocytes located in the skin?
Basally located
What is the melanocytes to basal keratinocytes ratio?
From 1:5 to 1:10 (constant irrespective of race)
What does the melanocortin 1 gene do?
Encodes MC1R protein (sits on cell surface), determines balance of pigment in skin and hair
What gives hair a red colour?
Phaeomelanin
What causes hair to be any colour except red?
Eumelanin
How can MC1R impact hair colour?
Changes phaeomelanin to eumelanin
What does one defective copy of MC1R cause?
Freckling
What does two defective copies of MC1R cause?
Red hair and freckling
What are freckles (ephilides)?
Patchy increases in melanin production that occur after sun exposure
Who are freckles most common in?
Fair skinned people and red heads
What do freckles reflect?
The clumpy distribution of melanocytes, islands with most melanocytes tan
What is the other name for actinic/solar lentigines?
Age/liver spots
What are some features of actinic lentigines?
Reflect UV exposure, found on face, forearms and dorsal hands, epidermis elongated rete edges, increases melanin and basal melanocytes
When do most melanocytic naevi occur?
Most naevi acquired in first two decades, 1% of babies born with congenital nauvus
What are the different size categories of naevi?
Small = <2cm diameter Medium = >2cm but <20cm diameter (giant garment-type lesions) Large = >20cm diameter (10-15% of melanoma, may need staged surgical excision)
How do usual type acquired naevi develop?
During infancy the melanocyte to keratinocyte ratio breaks down at a number of cutaneous sites (immune related), allows for formation of simple naevi
How many naevi does the average person have?
20-30 (normal naevi have low malignant potential)
How do acquired naevi develop over time?
Junctional naevus = melanocytes proliferate causing cluster of cells at DEJ (childhood)
Compound naevus = junctional clusters plus groups of cells (adolescence/early adulthood)
Intradermal naevus = all junctional activity has stopped so is now entirely dermal (adulthood)
What are some features of dysplastic naevi?
Generally >6cm, variegated pigment, border asymmetry, architectural and cellular atypia, epidermis not effaced, host reaction (fibrosis and inflammation)
What are the two kinds of dysplastic naevi?
Sporadic = not inherited, one to several atypical naevi, risk of malignant melanoma slightly raised Familial = strong family history of melanoma, autosomal inheritance, high penetrance, atypical naevi, lifetime risk of melanoma up to 100%
What are some examples of rarer naevi?
Halo naevi, Blue naevi, Spitz naevi
What are some features of halo naevi?
Have peripheral halo of depigmentation, show inflammatory regression and are overrun by lymphocytes
What are some features of blue naevi?
Entirely dermal and consist of pigment rich dendritic spindle cells, cellular variant may have mitoses and mimic melanoma
What are some features of Spitz naevi?
Described in 1948, used to be called benign juvenile melanoma, usually occur in < 20 year olds, consist of large spindle and/or epithelioid cells, may closely mimic melanoma, most are entirely benign but there is a malignant variant
Why can dysplastic naevi be difficult to distinguish from melanomas?
They have severe dysplasia
How do most malignant melanomas arise?
Arise de-novo, some come from dysplastic naevi
What is the female to male incidence of malignant melanoma?
2:1 (more common in females)
What age group are most likely to get malignant melanomas?
Incidence peaks in middle age, rare in childhood
Where is melanoma most common on the skin?
Sun exposed areas = scalp, neck, face, arms, trunk, legs (can occur anywhere, sun and UV exposure plays major role)
Where are some rare sites for melanomas to form?
Eyes, meninges, oesophagus, biliary tract and anus
When should you suspect a melanoma?
Change in shape, irregular pigmentation, bleeding, ulceration, development of satellite nodules, new pigmented lesion develops in adulthood
What are the four main types of melanoma?
Superficial spreading (SS) = most common, trunk and limbs Acral/mucosal lentiginous (A/ML) = acral and mucosal sites Lentigo maligna (LM) = sun damaged face, neck or scalp Nodular = varied sites but often trunk
How do all the types of melanoma except nodular develop?
Grow as macules when either entirely in-situ or with dermal microinvasion (RGP), eventually the melanoma cells invade the dermis forming an expansive mass with moles (VGP)
What are the only category of melanoma that can metastasise?
VGP melanomas
How do nodular melanomas develop?
No clinical or microscopic evidence of RGP, simply a nodule of VGP tumour (some say this is more aggressive)
What measures are used to decide melanoma prognosis?
Ulceration (strong adverse indicator) and Breslow depth (deepest tumour from granular layer in mm)
What are the different grades of Breslow depth?
pTis = melanoma in-situ (100% survival) pT1 = tumour is < 1mm (90% survival) pT2 = tumour is 1-2 mm (80% survival) pT3 = tumour is 2-4 mm (55% survival) pT4 = tumour > 4mm thick (20% survival)
What are some tumour features that can influence prognosis?
High mitotic rate, lymphovascular invasion, satellites, sentinel lymph node involvement
What occurs if there is spread of the melanoma to local dermal lymphatics?
Satellite deposits of malignant melanoma
Where can melanomas spread to after local dermal lymphatics?
Regional lymph node metastases = common pattern of disease progression, nodes excised (regional lymphadenectomy)
Where can a melanoma spread to once its in the blood?
Skin/soft tissue, heart, lungs, GI tract, liver, brain
What are some treatment options for melanomas?
Primary excision to give clear margins
Some also receive sentinel node biopsy (SNB)
If SNB positive then regional lymphadenectomy
What are the treatment options for advanced melanomas?
Chemotherapy, immunotherapy, genetic therapies (treatment of advanced disease difficult)
How much should the melanoma be cleared by when carrying out a narrow complete excision?
Depends on size In-situ = clear by circa 5mm Invasive but <1 cm thick = 1cm clearance Invasive and >1 cm thick = 2cm clearance Do an SNB if thicker than > 1cm or thinner with mitoses
What are some genetic treatments for melanomas?
Some acral melanomas have c-kit mutations and may be treated with imatinib
Melanomas on intermittently sun-exposed skin may have a BRAF mutation which is a potential target
Can test for mutations on paraffin fixed tissue
What is the BRAF gene?
Weak cytosolic proto-oncogene
What happens when the BRAF gene is mutated?
Drives cell proliferation by up-regulating MEK and ERK
What are some drugs developed to interfere with the BRAF pathway?
Dabrafenib, vemurafenib
What are some limitations of BRAF drugs?
Response times are limited, may be better in combination with MEK inhibitor, may be better in adjuvant setting for high risk lesions before metastases develop
