Pigmentation - physio, disorders, pigmented lesions Flashcards
What is melanin and its function
- Pigmented polymer
- protects DNA from UV radiation (200-2400nm)
- deactivates free radicals
What are the 3 types of melanin, location and production
- Eumelanin (hair/skin)
- Tyrosine ->(Tyrosinase) ->Eu-M
- Pheomelanin (blond/red hair)
- Tyrosine+cysteine ->(Tyrosinase) - >Pheo-M
- Neuromelanin (Neural tissue)
- unclear fx/production
How/Where is melanin made and distributed?
In melanocyte
- melanin in made in ER, packed in Gogi and released into melanomsome
- Melanosome is distributed to keratinocyte via dendritic processes of melanocyte
In keratinocyte
- melanosome is phagocytized into keratinocyte, and incorproated to cell membrane surrounding nuclei
What are melanocytes, embryology, location in the body
Melanocytes are spindle cells that produce melanin
- derived form neural crest cells in 10th wk GA
- migrate to epidermis (s. basale), hair follicle, mucous membrane, dermis (then named nevus cells), neural tissue, eye, inner ear
What is a nevus cell - and how does it differ from melanocyte?
- Nevus cell is a melanocyte whic hhas migrated into dermis
- Differs from melanocyte in that the nevus cell is:
- round/spindle (vs. dendritic)
- located in dermis (vs. s. basale)
- lives in clusters (vs. individual)
- Similar to melanocyte in that the nevus cell
- has small nuclei
- mitoses are rare
What 4 pigments are responsible for skin color? (list chromophore)
- Endogenous (melanocytes)->Brown w melanin
- Exogenous (diet) ->Yellow/orange w carotene
- Intravascular-> Blue w deoxyhemoglbin
- Intravascular ->Red w oxyhemoglobin
What determines the skin pigment at baseline?
- Density of melanosomes in the keratinocyte and the density of melanin in each melanosome
- Balance of Eumelanin (brown-blakc) vs Pheomelanin (yellow-red)
What factors control the color of skin
- Genetics
- Hormonal control
- melanotrophic hormones (MSH, ACTH, pregnancy, lipotropin)
- UV - stimulates release of melanotrophics from keratinocytes which stimualtes melanocytes to produce more melanin
What are hypopigmentary disorders
- Vitiligo
- Albinism
- Waardenburg
- Leptomeningeal melanocytosis
- Neurocutaneous melanosis
What is vitiligo
Hypopigment disorder with selective destruction of melnocytes in epidermis +/- follicles
- Onset 10-30yo, progressive
- sharply demarcated hypopigment macule which coalesce
Treatment
Non-op: Repigment with phototherapy, Depigment with hydroquinone, Tattoo
Operative: punch graft
What is albinism
Congenital hypopigmentary disorder - no production of melanin
- Onset birth
- No pigment in hair, eyes, skin
- normal density of melanocytes
List types of Nevocellular Nevi
Acquired
- Junctional nevus - at D-E jx
- Compund nevus - in dermis and epidermis
- Dermal nevus - in dermis only
Congenital
- GCMN
- Non-giant CMN
Special
- Halo nevus
- Spitz nevus
- Atypical nevus
When do acquired nevocellular nevi appear, change with age?
- Not present at birth
- progress from junctional ->compound ->dermal
What is a giant CMN?
- Pigmented nevus present at birth or shortly therafter, caused by abnormal migration of melanoblasts b/w 8-24th wk GA
- link to c-met oncogene
How is GCMN defined clinically
>20cm dimater
50% of body region
What conditions are associated w GCMN
- leptomeningeal melanocytosis
- NF
What are treatment options for GCMN?
Medical
- observe (dermoscopy/photo)
- Laser
- dermabrasion
- chemical peel
Surgical
- Serial excision, Tissue expansion, local flaps
What is the prognosis of GCMN
- <4% malignant transformation , usually <age>
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If child presents w GCMN, what are RFs for associated neurocutaneous melanosis
- GCMN on midline trunk/calvarium
- seizures, abnormal CNS development
- multiple satellite lesions
Workup for? neurocutaneous melanosis
MRI <6mths of age
What is a halo nevus?
Pigmented nevus w area of surrounding hypopigment
Treatment - expectant, excise if risk dysplastic nevus
What is a spitz nevus?
Benign Juvenile melanoma (spindle cell nevus of reed)
- Epid: majority <30yo, acquired or congenital
- Presentation; common H&N, symmetric small well circumscribed pigmented papule
Treatment
- observe
- excise if changes/cosmesis
What differentiates spitz nevus, atypical spitz nevus, malignant spitz?
Histology
- nest of spindle nevus cells in variable levels of dermis
What is your DDx of a congenital nevus?
- Nevis spillus
- beckers nevus
- acquired nevus
- lentigo nevus sebaceous
- mongolian spot
- cafe au lait
List benign melanocytic lesions
Epidermal
- Ephelis
- Lentigo
- Cafe au lait
- becker nevus
Dermal
- Blue nevus
- mongolian blue spot
- Nevus of Oto/Ito
What is lentigo pathology, types and presentation
- increased melanocytes in basal layer
- Lentigo simplex (younger pt) associated w LEOPARD, LAMB, PEutz Jagher
- Solar lentigo due to sun
- Malingna lentigo
What is an ephelide, pathology and presentation, treatment
Melanocytic lesion in the epidermis
- increased melanin, normal # melanocytes
- decrease in number w age
Tx
- laser, cryo
What is a Cafe au lait spot
Benign melanocytic lesion of the epidermis
- increased # melanocytes + acanthosis
- looks alike large brown patch
- present at birth, fades w age
What is a becker nevus
Benign HAIRY melanocytic lesion in ther epidermis
- increase #melanocytes and melanin granules
- appears in M, at puverty +/- hair, on back/shoulder, submammary
Treatment
- depilation, laser may lighten
What is a nevus spillus
Lentigo simplex ( melanocytic lesion in the epidermis) + smaller darker papule/macule
What is associated w cafe au lait spots
- McCune albright
- NF 1/2
What is your DDx for a pigmented macule <1cm
- Lentigo (solar)
- lentigo implex
- lentigo maligna
- LEOPARD syndrome
- LAMB syndrome
- Peutz Jeghers
- dysplastic nevus
- junctional nevus
What is the tyndall effect
Red (long) wavelengths pass by melanin but the shorter wavelengths (blue) are scattered, with some going back to skin surface
What is a mongolian spot
Congenital melanocytic lesion in dermis
- increased # of melnaocytes
- caused by abnornal migration of neural crest cells
- located in sacrococcygeal region, most common in hispanic, asian, native american
- uniform blue gray well demarcated lesion
- FADE by 3-4yrs of age
What is Nevus of ota and nevus of Ito
COngenital melanocytic lesion in the dermis
- located in 1st or 2nd branchial arch (Oto)
- or located on shoulder, deltoid, supraclav (Ito)
- occur at birth OR puberty, F:M
- confluence of blue black macules w associated brown spots
Treatment
Q-switched laser or NdYAG laser
What is Hori’s Nevus
Congenital melanocytic lesion in dermis
- looks like Nevus of Oto but bilateral and apepars in 40-50yo asians
What is a blue nevus
Congenital melanocytic lesion in dermis
- blue raised papule - may arise at any age
- increased # of melnocytes
- MM can arise from blue nevus
- Assocaited with syndrome LAMB if multiple present
- Lentiges
- Atrial myxoma
- Mucocutaneous myxomas
- blue nevi
- TREATMENT
- excise if >10mm or changing- margin 3-5mm
What is ur DDx of a blue nevus
- Nodular melanoma
- Cutaneous melanocytic melanoma
- Kaposi sarcoma
- Venous malformation
What are premalingnat lesions for melanoma
- GCMN
- Lentigo melanoma
- MIS
- atypical/dysplastic nevus
What is the histology of dysplastic nevus?
- discontinuous priliferation of atypical melanocytes with nest formation intraepidermal
What is the risk of melanoma from dyspalstic nevus?
- DN is a RF for development of melanoma
- DN is also a precursor for melanoma - 1/40 000 transform
What is lentigo malingna and te pahtology
COnsidered melanoma in situ on sun damaged skin
Path
- non-nested proliferation of atypical melanoctyes in an atrophic epidermis
Prognosis
- up to 30% trasnform into MIS, LMM or desmoplastic melanoma
WHat is MIS
Intraepidermal proliferation of atypical melnocytes w fully evolved atypia
- most commonly melanoma arises form MIS
What is FAMM
Familial Atypical Mole and Melanoma syndrome
- FDR or SDR with MM
- >50 nevi
- AD inheritance
Prognosis
- 10% risk of melanoma over 10yrs
What are syndromes associated with melanocytic lesions
- FAMM
- Waardenburg syndrome
- ALbright syndrome
- LAMB syndrome
- LEOPARD syndrome
- Peutz Jegher syndrome
- Central facial lentiginous
What is waardenburng syndrome
Congenital ABSENCE of melanocytes in hair, skin, ears, stria vascularis of ear
Associated w CL/P 7%
AD, due to defect in migration of NCC and melanin synthesis
Clinical features
- Skin; patchy hypo and hyperpigmented patches
- Hair:premature greying/white forelock
- Ear: SNL
- Eye: heterochromia, isohypochromia (pale blue), blepharophimosis, telecanthus
What is albright syndrome
Unilatreal polyostotic FD with cafe au lait spots and hyperfunctional endocrinopathies
What is LEOPARD syndrome
- Hypertelorism
- lentigo
- pulmonary stenosis
- genital abnormalities
- deafness
What is peutz jegher
- intestinal polyposis
- mucosal lentigo
What is LAMB syndrome
- Lentigo
- Atrial myxoma
- Mucocutaneous myxoma
- Blue nevi
What is centrofacial lentiginosous
- LEntigo simplex in horizontal band across face
- craniofacial microsomia
- CLP
What is epidermal nevus syndrome
- Craniofacial overgrowth
- Digital gigantism
- acquired nevocellular nevi
- Vascular mlaformations (CNS or cutaneous)
What is Neurocutaneous melanosis (= leptomeningeal melanocytosis)
Def. Nevocellular infiltrate into leptomeninges and brain parenchyma
Clinical features
- hydrocephalus
- seizure
- focal neurologic deficits
Presents around 2yr
RFs
- GCMN
- Congenital nevocellular nevus at midline on scalp, neck, spine
Do MRI before 6mths
Treatment - symptomatic. Delay excision due to poor prognosis
Prognosis
- asymptomatic: 60% risk of leptomeningeal melanoma (90% fatal)
- symptomatic (90% mortality)
