Pathology of pigmented lesions Flashcards
How can melanomas of odd body sites (e.g the liver) be explained?
Melanocytes become lost during migration from the neural crest and later become cancerous
What is the function of the melanocortin 1 receptor (MC1R) gene?
Production of the melanocortin 1 protein which is involved in the conversion of phaeomelanin into eumelanin (controls pigmentation of hair & skin)
What happens when there are mutations in the MC1R gene?
Freckling (one defective copy) and red-hair (two defective copies)
What is another name for freckles? What are freckles?
Ephilides. Patchy increases in melanin pigment
What are actinic/solar lentingines? How do they occur?
Age/liver spots. UV exposure causes changes within the epidermis (elongated rete ridges, increased melanocytes & pigment)
Where are actinic lentingines typically found?
Dorsal hands, face & forearms
What are melanocytic naevi? How are they acquired?
A broad catagory of moles/raised skin lesions. Congenital or developing over time (often within the first two decades of life)
How are congenital melanocytic naevi classified?
Small - 2cm but 20cm
What is the risk of progression to cancer with congenital melanocytic naevi?
Giant melanocytic naevi has a 10-20% risk of progression to melanoma
How are congenital melanocytic naevi treated?
Small lesions are generally left along while larger lesions may be surgically excised (may need to be a staged excision)
How are simple naevi acquired?
Melanocyte : keratinocyte ratio breaks down at specific cutaneous sites during childhood > simple naevus forms
What is the risk of progression to cancer with simple naevi?
Minimal
What is the relation to simple naevi and the immune system?
Immunosuppressed children develop more naevi
How do simple naevi develop?
Melanocytes proliferate creating a junctional naevi > compound naevi form as clusters of melanocytes form in the DEJ and dermis > intradermal naevi form when DEJ melanocyte clusters disappear and the naevi is entirely dermal
What is the presentation of dysplastic naevi?
Asymmetrical border, variegated pigment & generally >6mm diameter
What are the features of sporadic dysplastic naevi?
Not inherited, generally only a few naevi, slightly increased risk of progression to melanoma
What are the features of inherited dysplastic naevi?
Family history of melanoma (autosomal inheritance), high penetrance, many atypical naevi, high risk of progression to melanoma
What differentiates dysplastic naevi from typical naevi in terms of architecture and histology?
Dysplastic naevi is architecturally AND histologically abnormal (with evidence of inflammation and fibrosis)
What is the main distinguishing feature between melanoma and dysplastic naevi?
The epidermis is not effaced in cases of dysplastic naevi
What are halo naevi? Why does this occur?
A naevi surrounded by a ring of depigmentation. The body is attacking the melanocytes of the naevi and surrounding skin to cause regression
What are blue naevi?
Dermal proliferations of pigment rich dendritic spindle cells (may mimic melanoma)
At what age is halo naevi most common?
Late teens/early twenties
What is a spitz naevi?
A (commonly) benign skin tumour composed of large spindle and/or epithelioid cells which may resembled melanoma
Which age group most commonly develops spitz naevi?
Spitz naevi with prominent vasculature are commonly red in colour. T/F
True
How are malignant melanomas acquired?
De novo or transformation from a dysplastic naevi
What is the sex distribution of malignant melanoma?
More common in females
Which age groups most commonly develop malignant melanoma?
Middle aged (rare in children)
What is the aetiology of malignant melanoma?
Childhood sunburn, UV exposure, genetic risk, dysplastic naevi, skin type
When should malignant melanoma be suspected?
Change in shape of existing naevi, irregularly pigmented lesion, bleeding lesion, development of satellite nodules, ulceration, new pigmented lesion developing in adulthood
What are the four main types of malignant melanoma?
Superficial spreading, acral/mucosal lentiginous, lentigo maligna, nodular
What the the most common type of melanoma and where is it most commonly found?
Superficial spreading & on the arms and trunk
What is the second most common type of melanoma and where is it most commonly found?
Lentigo maligna & on sun-damaged skin of the face, scalp and neck
Where is nodular melanoma most commonly found?
Trunk
A mole which shows some patchy regression is typical of what?
Malignant melanoma
What are acral melanomas commonly misdiagnosed as?
Trauma related
What is the pathogenesis of non-nodular malignant melanomas?
Grow as macules in situ or with microinvasion (radio growth phase) > melanoma invades dermis forming expansile mass with mitoses (vertical growth phase) > metastases
RGP and VGP melanomas can both metastasise. T/F
False - only VGP melanomas can metastasise
Nodular melanomas have both a RGP and VGP. T/F
False - they do not have a RGP and instead present as nodules of VGP tumour
Which is the most aggressive form of melanoma?
Nodular
Describe Breslow classification of melanoma
pTis = melanoma in situ pT1 = tumour 4mm
What are the adverse prognostic factors of melanoma?
Increasing breslow classification, ulceration (suffix b), high mitotic rate, lymphovascular invasion, satellite lesions, sentinel lymph node involvement
How does melanoma spread?
- local dermal lymphatics (satellite deposits)
- regional lymph node metastases
- blood spread
How is melanoma treated?
Primary excision with clear markings, sentinal node biopsy, regional lymphadenectomy (questionable), chemotherapy, immunotherapy, genetic therapies
What is the process for excision of suspected melanoma?
Narrow excision (confirms diagnosis & breslow thickness) > re-excision margins based on breslow thickness
pTis = 5mm clearance pT1 = 1cm clearance pT2,3,4 = 2cm clearance & SNB
How may acral melanomas with c-kit mutations be treated?
Imatinib
When might BRAF-inhibitors be particularly useful in melanoma treatment?
Melanomas on intermittently sun exposed skin
What is BRAF? What happens when it mutates?
Weak cytosolic proto-oncogene. Drives cell proliferation via MEK and ERK
Name 2 BRAF inhibitors
Dabrafenib & vemurafenib
