melanin is not just for color.....

1. Dr . RANJAN DASH

2.  BASIS OF SKIN PIGMENTATION
 MELANOSOMES-types ,synthesis & maturation
 SYNTHESIS OF MELANIN
 TRANSPORT OF MELANIN
 DISORDERS OF HYPOMELANOSIS
 DISORDERS OF HYPERMELANOSIS

3. DIFFERENT COLOR OF SKIN IS
DUE TO :
1. Presence of CHROMATOPHORES
(pigment containing cells )
2. Presence & Distribution of
Pigments(coloured particles)
3. Hormonal and Neural control
REASON FOR VARIABLE SHADES OF
COLORATION
1. CAMOUFLAGE ( protective
resemblance),mimesis / crypsis
2. Aggressive Resemblance
Best example is CHAMELEON

7. Determined by : melanin
haemoglobin
carotenoids
At the level of Epidermis : Melanin , the major determinant and
carotenoids
At the level of Dermis - by oxygenated haemoglobin (red) in
capillaries - by reduced haemoglobin (blue) in venules
Constitutive skin colour : genetically predetermined
Facultative skin colour : induced by sun exposure(UV),
hormones & other regulatory factors

8.  derive from pluripotent neural crest cells
that differentiate into numerous cell
lineages including neurons, glia,smooth
muscle, craniofacial bone, cartilage, and
melanocytes.
 Progenitor melanoblasts migrate
dorsolaterally between the mesodermal
and ectodermal layers
 reach the hair follicles and the skin as
well as inner ear cochlea, choroid, ciliary
body, and iris.
 Melanoblast migration and
differentiation influenced by signaling
molecules Wnt, (ET)-3, bone
morphogenetic proteins (BMPs), steel
factor (SF) , and hepatocyte growth
factor .

9.  Melanoblasts migrate
dorsolaterally and then ventrally
around the trunk to the ventral
midline & differentiation into
melanocytes.
 During embryogenesis, melanin
producing melanocytes are found
diffusely throughout the dermis.
 By the end of gestation, active
dermal melanocytes disappear,
except in three anatomic locations
1. the head and neck,
2. the dorsal aspects of the
distal extremities
3. the presacral area
that coincide with the most common
sites for dermal melanocytosis and
dermal melanocytomas (blue nevi)

10.  Melanocytes in skin synthesize &
store melanin in cytosolic
organelles called melanosomes
 A constant need for synthesis &
transfer of melanosomes from
melanocytes to keratinocytes to
maintain cutaneous pigmentation.
 Melanocyte density/square mm
ranges from 550 to 1500, with the
highest concentration within face &
genitalia
 Association of a melanocyte with
approximately 30–40 surrounding
keratinocytes to which it transfers
melanosomes

11.  Follicular melanin unit undergoes cyclic
modifications along with the hair cycle
 located in the proximal hair bulb during anagen
 proliferate, migrate, and undergo maturation
during early to mid anagen.
 Melanogenesis and melanin transfer to
keratinocytes occurs throughout anagen.
 Melanocyteneventually apoptose during late
catagen
 in hair, melanocyte transfer melanin to
differentiated keratinocytes that ultimately form
the hair shaft.
 determine hair color by the amount of melanin
transferred, as well as by the ratio of eumelanin
(black–brown) to pheomelanin (red–yellow)

13. C . Ocular Melanocytes
- Unlike cutaneous melanocytes, ocular melanocytes are in contact
only with each other & don’t transfer melanosomes.
-Albinos may have visual abnormalities due to absence of melanin
D . Otic Melanocytes
- reside in cochlea & are important for hearing loss of otic melanocytes
may leads to deafness as in Waardenburg syndrome TYPE II

14. Depends upon :>
1) Melanogenic activity within the melanocyte
2) The proportion of mature melanosomes
3) Size of melanosomes
4) Type of melanin (eumelanin, or pheomelanin)
5) Melanosomes transfer & distribution within the
keratinocyte

16.  Definition: membrane-bound unique organelle
within the cytoplasm of melanocytes in which
in which melanin pigments are synthesized,
deposited and transported.
 And depending on the type of melanin
(eumelanin or pheomelanin) synthesized,
melanosomes can be divided into:
Eumelanosome and Pheomelanosome

24. 1) Transcription of proteins required for melanin
synthesis
2) Melanosome biogenesis
3) Sorting of melanogenic proteins into
melanosomes to initiate melanin synthesis
within the melanosome
4) Transport of the mature melanosomes to the
tips of melanocyte dendrites migrates via
microtubules
5) Transfer of melanosomes to keratinocyte

26. 1 .EXOCYTOSIS
- fusion of the melanosomal membrane with the melanocyte plasma membrane
- melanosome is released to the intercellular space
- phagocytosis by surrounding keratinocytes occur
2 .CYTOPHAGOCYTOSIS: projection of dendrites into keratinocyte cytoplasm
then keratinocytes cytophagocytose the tip of a melanocyte dendrite.
3. Fusion of melanocyte & keratinocyte plasma membrane create a space
through which melanosomes are transferred
4.Shedding of melanosome-filled vesicles followed by phagocytosis of the
vesicles by keratinocyte

29. A . Specific genes
B . Hormones: 1.MSH 2. ACTH 3. Estrogens
C . Biochemical factors: IL-1 2, IL-6 , TNF-alpha , basic
fibroblast growth factor (bFGF) 5- Endothelin-1, 3
D. External factors:
1- UV light (amount and wave-length)
2- melanocyte stimulating chemicals like
photosensitizers

35.  MITF, a basic-helix-loop-helix and leucine zipper transcription factor,
 the master gene for melanocyte survival
 A key factor regulating the transcription of the major melanogenic
proteins, tyrosinase, TRP-1, TRP-2 , PKC-β
 In melanocytes, it is the MITF-M isoform that stimulates transcription of
tyrosinase and PKC-b.
 MITF binds to conserved consensus elements in gene promoters, specifically
the M- (AGTCATGTGCT) and E- (CATGTG) boxes.
 MITF comprises a family of nine isoforms: (1) MITFM, (2) -A, (3) -B,
(4) –H , (5) -C, (6) -D, (7) -E, (8) -J, and (9) -Mc.
 MITF-M expression is highly specific for melanocytic cells.

36.  AMELANOSIS
 HYPOMELANOSIS
 HYPERMELENOSIS

37.  AD disorder of melanocyte development a/w Kit/SNCA gene
mutation
 Common characteristics include a congenital white forelock,
scattered normal pigmented and hypopigmented macules and a
triangular shaped depigmented patch on the forehead..
 In some cases, piebaldism occurs together with severe
developmental problems, as in Waardenburg
syndrome and Hirschsprung's disease.
 A kind of neurocristopathy, involving defects of various neural
crest cell lineages that include melanocytes, but also involving
many other tissues derived from the neural crest

38.  autosomal dominant
disorder
 White forelock
 Hypertelorism
 Congenital deafness
 Hypomelanotic
macules
 Heterochromic irides

39.  AD neurocutaneous syndrome
with skin lesions, mental
retardation and epilepsy
 Skin lesions are ash-leaf
macules, angiofibromas and
shagreen patches
 Ash-leaf macules - present at
birth in > 90% cases, so
important in early diagnosis
 Oval or ash-leaf shaped,
hypopigmented macules, look
prominent in Wood’s lamp Long
axis is axial on limbs and
transverse on trunk

40. HERMANSKYPUDLAK
SYNDROME
 autosomal recessive disorder
 Albinism and eye problems:
(photophobia), strabismus
(crossed eyes), and nystagmus
(involuntary eye movements)
 Bleeding disorders: due to
platelet dysfunction.
 Cellular storage disorders: The
syndrome causes a wax-like
substance (ceroid) to
accumulate in the body tissues
and cause damage, especially
in the lungs and kidneys
CHEDIAKHIGASHI
SYNDROME
A rare autosomal recessive disorder
that arises from a mutation of a
lysosomal trafficking regulator
protein,[ which leads to a decrease
in phagocytosis.
results in
recurrent pyogenic infection
s, albinism and
peripheral neuropathy

42.  May be epidermal or dermal
 Epidermal hyperpigmentation due to - Increased
melanin with normal number of melanocytes -
Increased number of melanocytes
 Dermal hyperpigmentation due to - Melanin from
epidermis transferred to dermis - Melanin formed
in dermal melanocytes - Melanin pigments
appears blue-gray due to Tyndall effect

43. A .EPIDERMAL
 Physiologic: Pigmentary demarcation lines, sun tanning
 Genetic and Developmental: Lentigines, Freckles, Peutz-Jeghers
syndrome, Melanocytic nevus, Café-au-lait spots, Xeroderma
pigmentosum, Becker’s nevus, Acanthosis nigrican
 Post-inflammatory: Eczema, Psoriasis, Lichen planus, Lupus
erythematosus, Scleroderma, Morphoea, Vagabond’s disease
 Nutritional: Kwashiorkor, Pellagra, Vit.B12, Vit.C, Folic acid
deficiency
 Physical: Trauma, Radiation dermatitis
 Endocrine: Melasma, Addison’s disease, Cushing’s syndrome,
Phaeochromocytoma, Acromegaly, Hyperthyroidism
 Neoplastic: Malignant melanoma, Seborrhoeic keratosis,
Pigmented basal cell carcinoma

44.  Genetic and Developmental: Mongolian spots,
Nevus of Ota/Ito, Incontinentia pigmenti
 Inflammatory: Stasis dermatitis, Post
inflammatory to eczema and fixed drug
eruption
 Chemicals and Drugs: Anti-malarials, OC Pills,
Minocycline, Clofazimine, Topical
hydroquinone, Tattoo

45.  Endocrine: Melasma
 Physical: Thermal burns, Post traumatic Infection:
Syphilis, Yaws, Pinta
 Neoplastic: Metastasis of melanoma
 Nutritional: Chronic nutritional deficiency Metabolic:
Hemochromatosis, Alkaptonuria, Macular / Lichen
amyloidosis
 Miscellaneous: Pigmented purpuric dermatosis,
Purpura

46.  Also known as Futcher’s or Voight’s
lines
 are borders of abrupt transition
between more deeply pigmented
skin and that of lighter pigmentation
 do not correspond to Blaschko’s lines
or dermatomal lines but to voigt’
lines
 Considered by some to be a variant
of normal pigmentation

47. Can be divided into five five categories:
 Group A - lines along the outer upper arms with variable extension
across the chest
 Group B - lines along the posteromedial aspect of the lower limb
 Group C - Paired median or paramedian lines on the chest, with
midline abdominal extension
 Group D - medial, over the spine
 Group E - bilaterally symmetrical, obliquely oriented, hypopigmented
macules on the chest

48.  Benign proliferations of cells at the dermo-epidermal
junction
 May be congenital or acquired
 Acquired nevi are more common
 Appear in infancy or childhood, slowly grow and mature
and then regress in older life
 Important for cosmetic reasons and as precursors for
melanoma (esp. in white)

49.  Round or oval, uniformly coloured and sharply bordered lesions
 Appear after birth
 Increase in frequency during childhood & adolescence and plateaus during middle age
 Most of them start as junctional nevi which are flat and histologically confined to
dermalepidermal junction
 Gradually mature to compound nevi which have nests and columns of nevus cells in
dermis along with the junctional component. These are raised, rounded, brown or black
 Intradermal nevi : Compound nevi mature to intradermal nevi with nevus cells only in
dermis having neuron like appearance. These are dome shaped, nonpigmented and may
have one or more coarse hair

52.  Acquired, pigmented, hairy
plaque common on trunk,
more common in males
 Appears in first or second
decade
 Common sites: shoulder,
chest, back
 May become verrucous with
hair growth and then remains
stable

53.  Circumscribed, brown
macules with irregular
margins, 2-5 cm in size
 Isolated CALM may occur
in 10-20% of normal
population
 No increase in the number
of melanocytes
 Five or more CALM of
size >0.5 cm in
prepubertal age group
and >1.5 cm in an adult
are strongly suggestive of
neurofibromatosis

54.  A common macular brown
coloured lesion seen on face in
males and females
 Common in pregnancy: Mask of
pregnancy (clears in few months)
 Forehead, nose, cheeks affected.
 The three clinical patterns are:
centrofacial, malar, mandibular
 Exacerbation on sun exposure
 Histologically may be epidermal,
dermal or mixed