Epidermal melanocytic lesions - pathology Flashcards
what embryo layer do melanocytes arise from
neuroectoderm
do melanocytes proliferate frequently
no; they have a low mitotic rate
where do melanocytes migrate to during fetal development
migrate from the neural crest to the eye (iris, retina, choroid), medulla oblongata, leptomeninges, schwann cells etc.
where do melanoblasts remain in the body after gestation (3)
- head and neck;
- dorsal aspects of distal extremities;
- pre sacral
where are blue naevi and pigmented epitheliod melanocytomas found
in areas where melanoblasts remain, especially in dorsal aspects of distal extremities
what cells are melanocytes closely related to
keratinocytes
what does a melanocyte-keratinocyte unit comprise of
1 melanocyte and 30-40 keratinocytes which recieve melanin granules produced by the melanocyte
what determines the colour of skin
the ratio of melanin in membrane bound granules: melanin lying free in cells
% of membrane bound granules in differnet skin types
black - 11%
brown - 37%
white - 85%
what are the 2 types of melanin found in skin and what kind of skin are they found in
- phaeomelanin (yellow-red, oval shape) - found in white skin;
- eumelanin (brown-black, round shaped) - found in black skin
how is melanin transferred to keratinocytes
via dendritic process
where is melanin located in keratinocytes
located above the nucleus (like an umbrella) and shields the nucleus from UV radiation
what 2 hormones affect melanin production
proopiomelanocortin (POMC) and alpha-melanocyte stimulating hormone (MSH)
what drives melanin production
UV exposure
what enzymes are most implicated in the pathways for melanin production
kinases
when do melanocytic lesions generally appear and why (lifespan)
start during puberty and end during menopause - the development of these are sensitive to sex hormones
what is an ephelis
freckle - increase in melanin within the basal keratinocytes (no increase in melanophages or melanocytes)
what is lentigo
linear proliferation of melanocytes in the basal layer, lens shaped
how does lentigo appear clinically
well circumscribed lens shaped dark lesion with soft edges
3 types of lentigo
acral; actinic; ink spot
what is a junctional naevus
a flat mole - progession of a lentiginous lesion - melanocytes arrange themselves in nests at the tip of epidermal rete ridges located at the junction of the epidermis and the dermis
junctional naevi clinical presentation
flat pigmented macule, commonly arises during puberty
what is a compound naevus
the presence of melanocyte nests at the junction and underlying dermis
how do the cells differ in compound naevi compared to junctional
the cells are smaller (size maturation) and not pigmented
what is the most common melanocyte lesion seen
compound naevi
where are the cells in compound naevi found
majority are in the dermis, some junctional nests present
what is an intradermal naevus
benign melanocytic lesion consisting only of nests in dermis
compound naevus presentation
A central raised area surrounded by a flat patch
intradermal naevus presentation
elevated, dome-shaped bump on the surface of the skin seen in middle ages pts
naevus natural progression
lentigo -> junctional naeuvus -> compound naevus -> intradermal naevus -> regression (senescence)
how do the cells in an intradermal naevus appear
nests of small uniform mature cells in the dermis that may be multinucleated; melanin is not usually seen in these cells
what is a spitz naevus
a benign lesion that shows enlarged melanocytes with a prominent nucleoi; may have kamino bodies at the epidermodermal junction; may show collagen deposition
what are kamino bodies
pink “blobs” that consist of basement membrane material (collagen type IV/VII, fibronectin etc.)
spitz naevus clinical presentation
may mimic melanoma - central homogenous black-blue pigmentation surrounded by
streaks, pseudopods, or finger-like projections, which are regularly and symmetrically distributed at the periphery
what are blue naevi
a type of melanocytic naevus in which spindle-shaped or, less commonly, ovoid naevus cells, are located deep within the dermis
how do blue naevi occur
cells stop their migration to the epidermis and remain in the dermis, they produce melanin which is picked up by macrophages and histocytes
why doe blue naevi appear blue
due to the depth of the melanin in the dermis and the Tyndall effect
what is the Tyndall effect
the preferential absorption
of long light wavelengths by melanin and the scattering of
shorter wavelengths, representing the blue end of the spectrum, by collagen bundles
what is a dysplastic naevus
a naevus that extends in an irregular manner beyond the border of the intradermal component - shouldering phenomenon
junctional naevus vs dysplastic
junctional - will
usually end in line with the intradermal component, located at the tips of the rete ridges, no nuclear atypia, no fibrosis;
dysplastic - extends past the jucntional boarder irregularly (shouldering phenomemnon), junctional nests will be present between the rete ridges and will bridge adjacent rete ridges (architectural disorder), enlarged, variable nuclei, characteristic layers of
eosinophilic fibrosis surrounding the elongated epidermal rete ridges, melanophages in the superficial dermis, lymphohistiocytic inflammatory infiltrate
how is high grade vs low grade assessed in dysplastic naevus
cytological atypia
how does lamella fibroplasia occur (pathway)
basal keratinocytes/ melanocytes die -> melanin released -> picked up by macrophages forming melanophages -> invoked healing sequence ->chronic inflammation followed by fibrosis
what is regression
the process of lymphocitic inflammation -> melanophase accumulation -> vascular proliferation -> fibrosis in a melanocytic lesion
what does regression look like clinically
melanocytic pattern but with a clearing (white/pale area) in the middle of the lesion where melanin is being taken up by melanophages
what other lesions are characterised by lymphocytic reaction and regression
kertatoacanthoma and melanoma
what is the critera used for melanoma diagosis
A - asymmetry
B - boarder irregularity
C - conspicuous junctional activity
D - dermal mitotic activity
what are the 4 main types of malignant melanoma
- lentigo maligna/LMM
- superficial spreading
- nodular
- acral-lentiginous
which melanoma is not related to sun exposure
acral lentiginous melanoma
lentigo maligna melanoma -pathology
- lentiginous proliferation of single cells at the epidermodermal
junction, which can also colonise hair follicles; - The dermis usually shows a lot of sun damage and the epidermis is often quite atrophic with flattening of the rete ridges;
- When lentigo maligna invades, the malignant cells will be present in the
dermis where they can have an epithelioid or spindle cell
appearance
superficial spreading pathology
lots of chaotic cells arranged in nests and single cells at the junction with prominent pagetoid extension of malignant melanocytes into
the upper layers of the epidermis
nodular melanoma pathology
- a nodule of pleomorphic, mitotically active melanocytes in the dermis;
- no junctional activity beyond the border of the main lesion;
- often arises
on intermittently sun exposed skin
acral melanoma pathology
lentiginous proliferation of
single cells along the epidermodermal junction and when it invades comprises nests of pleomorphic melanocytes within the dermis
what are the 2 growth phases in melanoma
radial and verticle
what is the radial growth phase
growth horizontally - don’t have capacity to get into lymphatics and metastasise
what is the vertical growth phases
grow vertically/downwards into the dermis - can metastesise
clinical appearance of a tumour in the radial growth phase
flat, pigmented lesions
clinical appearance on transformation from radial to vertical growth phase
nodule forms on an otherwise flat pigmented lesion
why can tumours not metastasise in the radial phase
the majority of the malignant melanocytes are present within the epidermis and at the epidermodermal junction in a radial growth phase
what does pleomorphic mean
nuclei vary in shape and size
what would a melanoma biopsy show (3)
- pleomorphic cells - some show prominent eosinophilic
nucleoli, reflecting their increased metabolic activity; - nests
- mitotic activity
what does a biopsy of lentigo maligna show
irregular proliferation of single dark atypical
melanocytes distributed along the base of the
epidermis -> when it invades it forms nests of malignant cells, characteristic of invasive lentigo maligna melanoma
what does a superficial spreading melanoma biopsy show
- chaotic proliferation of very atypical melanocytes distributed at all levels of the
epidermis in a buckshot pattern (pagetoid spread); - When this tumour invades the dermis it forms nests of mitotically active pleomorphic cells
acral melaonoma biopsy
- crowded proliferation of single atypical melanocytes distributed along the base of the thick epidermis;
- these single cells also extend upwards into all layers of the epidermis
what is Breslow’s thickness
a measure of the granular layer of the epidermis to the deepest melaoncyte in the dermis -> the thicker the layer the more likely it will metastesise
what is used to determine the T staging on the melanoma
the breslow thickness
what else impacts the T staging of melanoma (2)
- ulceration;
- mitotic activity;
- perinerual invasion - increases risk of vascular invasion and metastasis
what marker can be used for identifying lymphatic channels in tissue sections
D240 - an immunohistochemical marker
what is a good prognostic sign in melanoma
tumour infiltrating lymphocytes - indicate that the host’s immune system is responding to the tumour
what contributes to the N classification of staging melanoma
microstellites - small deposits of tumour away from the main tumour mass (within 2cm, if further then they are ‘in-transit’ metastesies)
mutation in what gene is highly involved in melanoma
p53
what other pathway is implicated in melanoma
MAP-kinase
