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Melanocytic Lesions
Of Skin
Except Melanoma
 Dr Nidhi Rai
• Melanocytic proliferations are composed of one or
more of three related types of cells:
• Melanocytes,
• Nevus cells,
• Melanoma cells
Each of which may be located in the epidermis or in the
dermis
NEVUS CELL MELANOCYTE MELANOMA
CELL
Type Round or spindle
shaped
Dendritic Round or spindle
shaped
Grouping Clusters Solitary Clusters & sheets
Nuclei Vesicular with
nucleolus
Small & regular
dark staining
shrunken
Large & atypical
Mitosis Rare Rare Common &
atypical
 Melanocytes are solitary Dendritic cells that generally are separated from
one another by other cells (keratinocytes or fibroblasts).
BENIGN PIGMENTED LESIONS
Epidermal
melanocytes
Dermal
melanocytes
Benign
tumor of
nevus cells
FROM EPIDERMAL MELANOCYTES
Ephelides
Solar lentigenes ( actinic/senile lentigo)
Lentigo Simplex
Melanotic macule of Albright’s syndrome
Becker’s melanosis
Freckle (EPHELIDES)
• Usually appear in first 3 yrs of life.
• Common – Red hairs / blue eyes.
• Due to increased sun induced
melanogenesis.
• 1-3 mm red brown macule over sun
exposed skin.
• Further exposure to sun deepens the
pigmentation.
Microscopy :
• Hyperpigmentation of the
basal cell layer
• No elongation of the rete
ridges
• No obvious increase in the
concentration of melanocytes.
• Represent a hyperplastic and
hyperactive response of
melanocytes to UV light.
Melanotic Macule Of Albright’s
Syndrome
• Albright’s syndrome –
 Unilateral polyostotic fibrous
dysplasia.
 Precocious puberty in females.
 Melanotic patches.
(Large and few in number ,
located on only one side of the
midline, and have a jagged,
irregular border.)
Microscopy:
• Hyperpigmentation of the basal layer and both the number and
size of the melanocytes are normal .
D/D:
• Cafe-au-lait patches of neurofibromatosis ( Smooth border of
lesions)
Lentigines
• Latin word – Lenz , meaning lens or lentil, clinically referring
to the appearance of small ovoid or lens shaped pigmented
spot.
• Macular hyperpigmentations in which the number of epidermal
melanocytes is increased & no nests of melanocytes as in nevi.
• Lentiginous proliferation – basal proliferation of melanocytes
as single cells with elongation of rete ridges.
Solar Lentigo (Actinic Lentigo)
• Multiple scattered small brown
macules on sun-damaged areas
• Male
• Increase in number with age (Senile
lentigines).
• Microscopy:
 Elongated & clubbed/ tortuous rete
ridges c/o pigmented basaloid cells.
 Slight to moderate prominence of
melanocytes along basal layer
without contiguous proliferation.
 Upper dermis- Elastosis &
scattered melanophages.
Differential diagnosis –
• Lentigo simplex
• Lentigo maligna
Lentigo Simplex
• Early onset (Childhood).
• Unrelated to sun exposure.
• Few scattered small, symmetric and
well circumscribed evenly pigmented
macules.
• Microscopy:
• Increased number of melanocytes in
epidermal basal layer and focally lie in
contiguity.
• Elongated rete ridges-heavily
pigmented & have branching
downgrowths -dirty feet appearance.
• N0 nests
D/D- Junctional nevus
Becker’s Melanosis
• Malformation involving the epidermis ,
pilosebaceous units & erector pilli muscle.
• Increased androgen receptors & heightened
sensitivity to androgen – occurs after
puberty.
• Large U/L poorly demarcated patch with
hyperpigmentation & hypertrichosis.
• Shoulder , back or chest of a adult male
Microscopy :
• Acanthosis, hyperkeratosis
• Regular elongation of rete
ridges
• Hyperpigmentation of basal
layer, number of melanocytes
increased
• Increased smooth muscle
fibers in dermis
Clinical Basal
Layer
Melano-
cytes
Features
Ephelids Sun exposed
skin
Decreases with
age
Inc. Melanin Normal
Melanotic
Macule Albrights syn. Inc. Melanin Normal
Beckers
Melanosis
U/l
hypertrichosis Inc. Melanin Increased
Elongated rete,
smooth muscle
fibres in dermis
Solar
Lentigo
Sun exposed
skin
Increases with
age
Inc. Melanin Increased
No contiguity
Elongated rete,
solar elastosis
Lentigo
Simplex
Not related to
sun exposure
Inc. Melanin Increased
Focal contiguity
Elongated rete
(Dirty feet
appearance)
From Dermal Melanocytes
Persistent
Mongolian
Spot
Nevi
of
Ota & Ito
Blue nevus-
common ,
cellular ,
combined
• Melanocytes appear in dermis- 10 th week of gestation
• Except in dermis of scalp, extensor aspect of extremeties and
sacral region
• Blue colour- Tyndall Phenomenon- decreased reflectance in
longer wavelength region( red, yellow ,orange)
Migrate into epidermis Undergo cell death
Mongolian Spot
• Appears at birth
• Disappears at 3-4years.
• Sacrococcygeal region.
• Uniformly blue discoloration
No pigmentary changes in epidermis
No melanophages
Elongated,slender,slightly wavy dentritic
cells containing melanin granules ,between
the collagen bundles in the lower dermis
Nevus Of Ota
• Oculodermal melanosis.
• Present at birth.
• Ill defined brown to slate blue U/L lesion
in distribution of ophthalmic &
maxillary division of trigeminal nerves.
• Malignant changes – rare
• Associated with persistent mangolian
spots.
Nevus Of Ito
• U/L slate blue mottled , macular
pigmentation.
• Regions Supplied by posterior
supraclavicular & lateral brachial
cutaneous nerves (supraclavicular,
scapular & deltoid regions)
Microscopy:
Hyperpigmentation of epidermis Bipolar melanocytes dispersed singly in
superficial dermis
Blue Nevus
• Benign, localized pigmented lesions.
• On skin 3 types –
 Common blue nevus
 Cellular blue nevus
 Combined nevus
• Childhood – extremities & scalp
• Histologically common feature - Presence of dendritic
melanocytes in reticular dermis associated with variably
stromal fibrotic response.
Common Blue Nevus
• (<10 mm) bluish-grey well
circumscribed dome shaped
papule.
• Near dorsa of the hands & feet ,
scalp.
• Microscopy:
 Normal epidermis.
 Pigmented spindle and dendritic
melanocytes in a focal area of the
reticular dermis, associated with
thickened collagen bundles.
 typically larger and their
density is much greater
 Cells have plenty of
melanin.
 Melanophages are seen, but
not numerous or dense.
 Melanocytes - positive for
S-100, HMB-45 & Melan-
A.
• D/D –
Dermatofibroma
( If minimally pigmented)
Cellular Blue Nevus
• blue nodule,1 to 3 cm in diameter.
• buttocks or in the sacrococcygeal
region.
• Microscopy:
• bulky, heavily pigmented cellular
tumor .
• spanning the reticular dermis.
• Extend into the subcutis forming
a bulbous expansion
( Dumb Bell Pattern).
• comprising of deeply pigmented dendritic melanocytes +
cellular islands large spindle shaped or epitheloid cells with
ovoid nuclei and abundant pale cytoplasm often containing
little or no melanin.
• Melanophages often seen.
• Four histological subtypes:
1. Mixed biphasic
2. Alveolar
3. Fascicular or neuronevoid (monophasic spindle-cell type)
4. Atypical varieties
Spindle cells lie in contiguity with one
another, unlike the cells of common
blue nevi, most of which are separated
from one another by collagen bundles
Mixed biphasic pattern , with ovoid
islands of polygonal cells with somewhat
clear cytoplasm alternating with spindle
cells, the latter often pigmented.
SPECTRUM OF HP FEATURES OF INTRADERMAL
MELANOCYTIC PROLIFERATIONS
MELANO-
CYTOSES
COMMON
BLUE NEVUS
CELLULAR BLUE
NEVUS
COMBINED
NEVUS
Paucicellular,
Interstitial
proliferation of
bland Dendritic
melanocytes
sclerotic stroma
+ heavily
pigmented
lesion larger, deeper
+Oval melanocytes
with abundant
cytoplasm with little
or no melanin
MF+
blue nevus with
an overlying
melanocytic
nevus or to
other
combinations of
benign nevi
Arising From Nevus Cell - Melanocytic
Nevus
CONGENITAL ACQUIRED
• Junctional
• Compound
• Intradermal
SPECIAL
VARIANTS
• Spitz
• Dysplastic
• Halo
• Deep
Penetrating
• Recurrent
• Pigmented
Spindle Cell
Tumor Of Reed
• Balloon Cell
• Benign non neoplastic proliferation of melanocytes
• Pigmented or nonpigmented lesions ,< 5 mm in diameter.
• Adolescence or early adulthood, rarely at birth.
• Cells arranged in cohesive nests with relative uniformity of the
nevus cells and fairly regular spacing of the nests.
• Nests located at the tips of the rete ridges (for junctional and
compound nevi)
CONGENITAL NEVI
• Found in 1% of newborn.
• Usually solitary – trunk , lower
extremities and scalp
• larger than acquired nevi
measuring >1.5 cms.
• Giant congenital nevi,(garment
nevi)- > 20 cms
• Giant congenital melanocytic nevi
– increase risk of the development
of melanoma.
• Microscopy:
 May be junctional, compound
or intradermal
 Presence of melanocytes
around and with in the
adenxae ,nerves , vessel wall.
 Nevus cells extend between
collagen fibers singly or in a
Indian file pattern-
characteristic feature.
nevus is very broad and deep-
epidermis-dermis-fat
spindle shaped heavily pigmented
ACQUIRED NEVI
• More prevalent in boys, more in fair skin and blond or red
hair.
• Undergo progressive maturation with increasing age of the
lesion.
• The lesion become stable after growing to some size and may
even involute. With advancing age there is progressive
decrease in the number of nevi
Histopathological types Clinical types
Junctional Flat macules
Compound Pappilomatous
Intradermal Dome shaped,
pedunculated lesion
Junctional Nevus
• Well circumscribed brown
to black macules, any where
• childhood or early adolescence
• Microscopy:
 Presence of well circumscribed
nests of cohesive melanocytes
either within lower epidermis or
bulging into dermis.(theque)
 Originating from tips and sides
of rete ridges.
• Variable lentiginous melanocytic hyperplasia.
• No continuous proliferation of melanocytes in the
suprapapillary regions of the epidermis between the rete
ridges.
• Melanophages in dermis
• D/D –
1. Lentigo simplex - no theques
2. Junctional lentiginous melanocytic nevus- not circumscribed
Compound Nevus
• Elevated pigmented papule.
• Microscopy:
 Junctional melanocytic theques
+ dermal population of
melanocytes (Nevus cell nests
are present in the epidermis as
well as appearing to ‘drop off’
into the dermis).
 Periadenexal & adventitial
dermis spared Compound nevus: both junctional and
dermal nests of nevus cells
• The nevus cells change their morphology as they go deeper
into the dermis. Three morphologic subtypes of nevus cells
are recognized, from superficial to deep:
TYPE LOCATION SHAPE MELANIN
A
(epithelioid)
upper dermis Round to polygonal
with abundant
cytoplasm
variable
B
(lymphocytoid)
mid-dermis same but smaller
than type A
less than A
C lower dermis elongated spindle
shaped ( fibroblast)
rarely contain
INTRADERMAL NEVUS
• Adults, dome shaped lesions
flesh coloured
• Microscopy:
 Upper dermis -
 nests and cords of nevus cells
concentrated around
pilosebaceous units.
 Multinucleated nevus cells -
small nuclei in a rosette-like
arrangement or close together
in the center of the cell.
 Lower dermis –
 Less cellular c/o spindly cells,
similar to that of the fibers in a
neurofibroma(neurotized nevus).
 In other areas, the nevus cells
lie within concentrically
arranged structure , resemble
Meissner's tactile bodies.
 Clefts - between some nests of
nevus cells and the surrounding
epidermis as well as stroma,
simulates a lymphatic space and
mimics lymphatic invasion
cell nests having a neuroid
differentiation
SPECIAL VARIANTS
BALLOON CELL NEVUS
• Clinically indistinguishable from
melanocytic nevi
• Microscopy-
 Epidermis - Balloon cells seen
singly or in groups or absent .
 Dermis - arranged in lobules of
varying size admixed with
ordinary nevus cells.
 Large cells , small round centrally
placed nucleus with empty , finely
granular or vacuolated cytoplasm
 Large vacuoles – Enlargement and coalescence of
degenerating melanosomes.
 Stains for lipid, glycogen and acid or neutral
mucopolysaccharide – negative.
D/D –
 Large adipocyte in intradermal nevi – Flattened nucleus at
periphery.
 Clear cell hidrenoma – Presence of PAS positive glycogen &
keratin.
SPITZ NEVI
(benign juvenile melanoma )
• Spindle &/or epitheloid cell nevus.
• Children & young adults
• Head & neck and extremities
• Solitary dermal dome shaped small
pink nodule
• Majority – Compound , 20%
intradermal, 5-10% junctional
Microscopy
• Small , symmetric, well circumscribed.
• epidermis shows hyperplasia &
elongated rete ridges .
• Nevus cell - Spindle cells & Epitheloid cells
• Arrayed as epidermal nests grouped in a vertical orientation
(bunches of bananas or raining down pattern), with clefting
artifact.
• little or no pagetoid spread pattern.
• Maturation of the cells with increasing depth.
• Bizarre giant cells may be seen.
• Presence within the epidermis of red globules, form large
bodies through coalescence – Kamino Bodies , apoptotic
degenerating melanocytes.
• Little or no melanin.
• At the dermal base - no mitoses
• Lymphocytic infiltration in dermis
• Variants:
1. Desmoplastic
2. Hyalinizing
3. Angiomatoid
large cells, with abundant amphophilic
cytoplasm, which may be spindled or
polygonal in shape (large spindle and/or
epithelioid melanocytes
Maturation in a spitz nevus
Globoid eosinophilic bodies (kamino bodies)
PAS & TRICHOME +VE
Diagnostic criteria :
Major Criteria Minor Criteria
• Symmetry
• Cell type –large spindle
and epithelioid cells
• Maturation
• Absence of pagetoid
spread
• Kamino bodies
• Junctional cleavage
• Superficial multinucleate
nevus cells
• Perivascular inflammation
• No atypical mitoses
• Solitary nevus cells in deeper
parts
• IHC :
 react for HMB45, Melan A/MART1, NK1/C-3 and S100. Of
importance is stratification seen with HMB45- deeper cells stain
intensely than superficial cells, Stratification also seen with
cyclin D1
• D/D –
 Spitzoid melanoma- no maturation, atypical mitoses, pagetoid
spread
 Pigmented spindle cell nevus of reed- seen in blacks & is heavily
pigmented
 Pyogenic granuloma, mastocytoma, juvenile xanthogranuloma,
warts, melanocytic nevi
PIGMENTED SPINDLE CELL NEVUS
• 3-6 mm , deeply pigmented , flat or slightly raised papules.
• Young adult, female,- lower extremities.
• Microscopy:
 Symmetrical - proliferation of elongated spindle shaped
heavily pigmented melanocytes in nests at the dermo-
epidermal junctions.
 Vertically oriented & blend with adjacent keratinocytes
rather than forming clefts as in spitz nevi.
 Characteristic accumulation of melanophages.
 Base of the lesion – superficial reticular dermis, show
lymphocytic response.
Kamino bodies may be seen in epidermal compartment
D/D-
 Melanoma of the superficial spreading type
Pigmented spindle shaped
nevus
Melonoma
( Superficial spreading)
• Small , symmetric , sharply
demarcated lateral margins.
• Cells Uniform from side to
side
• Descend into the dermis and
mature along nevus line.
•Abnormal mitosis in
uncommon
• Large , asymmetric with lateral
extension.
• Cellular variabilty.
• Little or no maturation
• Common
Deep Penetrating Nevus
(Plexiform Spindle Cell Nevus)
• 2nd and 3rd decades
• Head, neck and shoulder
• 2- 9 mm, darkly pigmented
papules and nodules.
• Microscopy –
 Compound type
 Circumscribed and pyramidal in
shape with a broad base abutting
the epidermis and apex towards
the subcutaneous fat.
Composed of loosely arranged
nests or plexiform fascicles
of large pigmented spindle
and epithelioid cells interspersed
with melanophages
• Slight nuclear pleomorphism but inconspicuous nucleoli
• Mitoses absent.
• D/D –
Melanoma- Marked atypia
Pagetoid spread
Irregular acanthosis & thinning
HALO NEVUS
• Sutton's nevus or nevus depigmentosa
centrifugum
• Pigmented macule surrounded by a depigmented
zone or halo.
• children & young adults, Back.
• Almost any of the types.
• Pathogenesis :
 Circulating Abs against neoplastic melanocytes & inflammatory
cells in the lesion( T lymphocytes both Ag presenting and
cytotoxic)
 The halo - due to cross reaction between a field of melanocytes
and the T cells.
Microscopy:
• Common – Inflammatory halo nevus.
• Early - nests of nevus cells embedded in a dense
inflammatory infiltrate in the upper dermis and at the
dermoepidermal jn.
• Later - scattered nevus cells tend to predominate over nests.
apoptotic cells also seen.
• Inflammatory infiltrate -lymphocytes and few melanophages.
• The region of halo nevus at first shows reduction in the
number of melanocytes and later their complete absence
At the periphery of the nevus, the halo is a region where pigment and
melanocytes are reduced or absent, and there may be a subtle
lymphocytic infiltrate at the dermal-epidermal junction
Types Inflammation Involution Halo
Inflammatory Present Present Present
Non inflammatory Absent Absent Present
Halo nevus phenomenon Present May involute Absent
Halo dermatitis around
nevus ( Mayerson’s
eczematous nevus)
Temporary
reaction
surrounding a
nevus
Present
Recurrent Nevus (Pseudomelanoma)
• A nevus may recur following an incomplete excision
presenting clinically as hyperpigmented lesions
• Confined to the region of the scar and typically presents with
in weeks of the surgical procedure.
• Microscopy:
 Lentiginous and junctional theques above the dermal scar.
 No epidermal ridges.
 Dermal fibrosis.
 Nevus cells are present in the deep dermis and at the edge of
the scar.
• HMB45 stains more
prominently in the recurrent nevi
than the original lesion.
• D/D –
RECURRENT MELANOMA -
 Sharp circumscription of the
intraepidermal component,
 Presence of melanocytes in nests
and as single units mostly at the
junction and the typical nevoid
cells of the preexisting dermal
melanocytic nevus beneath a scar
are helpful clues
Dysplastic Nevus
• present as macules often with a
central papule, have irregular
border and irregular pigmentation >
5 cms.
• Multiple or solitary
• Adults
• Trunk , lower legs ( Females)
• Shows cytological and architectural
atypia & regarded as intermediate
b/w common nevi and superficial
spreading melanoma
Junctional / compound nevi
Architectural Abnormality-
• Shoulder phenomenon
• stromal response with fibrosis.(includes lamellar and
concentric fibroplasias)
• Lentiginous proliferation of melanocytes – not contiguous
nevus cells- spindle / epitheloid
• Random cytological atypia in epidermal component- large
pleomorphic nuclei.
Single & nested melanocytes , lamellar
fibroplasia
Cytologic atypia
D/D – Radial growth phase melanoma
References
• Levers histopathology of skin
• Weedons pathology
• Mckee
• Sternberg
Thank You

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Melanocytic lesion of skin ( final)

  • 1. Melanocytic Lesions Of Skin Except Melanoma  Dr Nidhi Rai
  • 2. • Melanocytic proliferations are composed of one or more of three related types of cells: • Melanocytes, • Nevus cells, • Melanoma cells Each of which may be located in the epidermis or in the dermis
  • 3. NEVUS CELL MELANOCYTE MELANOMA CELL Type Round or spindle shaped Dendritic Round or spindle shaped Grouping Clusters Solitary Clusters & sheets Nuclei Vesicular with nucleolus Small & regular dark staining shrunken Large & atypical Mitosis Rare Rare Common & atypical
  • 4.  Melanocytes are solitary Dendritic cells that generally are separated from one another by other cells (keratinocytes or fibroblasts).
  • 5.
  • 7. FROM EPIDERMAL MELANOCYTES Ephelides Solar lentigenes ( actinic/senile lentigo) Lentigo Simplex Melanotic macule of Albright’s syndrome Becker’s melanosis
  • 8. Freckle (EPHELIDES) • Usually appear in first 3 yrs of life. • Common – Red hairs / blue eyes. • Due to increased sun induced melanogenesis. • 1-3 mm red brown macule over sun exposed skin. • Further exposure to sun deepens the pigmentation.
  • 9. Microscopy : • Hyperpigmentation of the basal cell layer • No elongation of the rete ridges • No obvious increase in the concentration of melanocytes. • Represent a hyperplastic and hyperactive response of melanocytes to UV light.
  • 10. Melanotic Macule Of Albright’s Syndrome • Albright’s syndrome –  Unilateral polyostotic fibrous dysplasia.  Precocious puberty in females.  Melanotic patches. (Large and few in number , located on only one side of the midline, and have a jagged, irregular border.)
  • 11. Microscopy: • Hyperpigmentation of the basal layer and both the number and size of the melanocytes are normal . D/D: • Cafe-au-lait patches of neurofibromatosis ( Smooth border of lesions)
  • 12. Lentigines • Latin word – Lenz , meaning lens or lentil, clinically referring to the appearance of small ovoid or lens shaped pigmented spot. • Macular hyperpigmentations in which the number of epidermal melanocytes is increased & no nests of melanocytes as in nevi. • Lentiginous proliferation – basal proliferation of melanocytes as single cells with elongation of rete ridges.
  • 13. Solar Lentigo (Actinic Lentigo) • Multiple scattered small brown macules on sun-damaged areas • Male • Increase in number with age (Senile lentigines). • Microscopy:  Elongated & clubbed/ tortuous rete ridges c/o pigmented basaloid cells.
  • 14.  Slight to moderate prominence of melanocytes along basal layer without contiguous proliferation.  Upper dermis- Elastosis & scattered melanophages. Differential diagnosis – • Lentigo simplex • Lentigo maligna
  • 15. Lentigo Simplex • Early onset (Childhood). • Unrelated to sun exposure. • Few scattered small, symmetric and well circumscribed evenly pigmented macules. • Microscopy: • Increased number of melanocytes in epidermal basal layer and focally lie in contiguity. • Elongated rete ridges-heavily pigmented & have branching downgrowths -dirty feet appearance. • N0 nests D/D- Junctional nevus
  • 16. Becker’s Melanosis • Malformation involving the epidermis , pilosebaceous units & erector pilli muscle. • Increased androgen receptors & heightened sensitivity to androgen – occurs after puberty. • Large U/L poorly demarcated patch with hyperpigmentation & hypertrichosis. • Shoulder , back or chest of a adult male
  • 17. Microscopy : • Acanthosis, hyperkeratosis • Regular elongation of rete ridges • Hyperpigmentation of basal layer, number of melanocytes increased • Increased smooth muscle fibers in dermis
  • 18. Clinical Basal Layer Melano- cytes Features Ephelids Sun exposed skin Decreases with age Inc. Melanin Normal Melanotic Macule Albrights syn. Inc. Melanin Normal Beckers Melanosis U/l hypertrichosis Inc. Melanin Increased Elongated rete, smooth muscle fibres in dermis Solar Lentigo Sun exposed skin Increases with age Inc. Melanin Increased No contiguity Elongated rete, solar elastosis Lentigo Simplex Not related to sun exposure Inc. Melanin Increased Focal contiguity Elongated rete (Dirty feet appearance)
  • 19. From Dermal Melanocytes Persistent Mongolian Spot Nevi of Ota & Ito Blue nevus- common , cellular , combined
  • 20. • Melanocytes appear in dermis- 10 th week of gestation • Except in dermis of scalp, extensor aspect of extremeties and sacral region • Blue colour- Tyndall Phenomenon- decreased reflectance in longer wavelength region( red, yellow ,orange) Migrate into epidermis Undergo cell death
  • 21. Mongolian Spot • Appears at birth • Disappears at 3-4years. • Sacrococcygeal region. • Uniformly blue discoloration
  • 22. No pigmentary changes in epidermis No melanophages Elongated,slender,slightly wavy dentritic cells containing melanin granules ,between the collagen bundles in the lower dermis
  • 23. Nevus Of Ota • Oculodermal melanosis. • Present at birth. • Ill defined brown to slate blue U/L lesion in distribution of ophthalmic & maxillary division of trigeminal nerves. • Malignant changes – rare • Associated with persistent mangolian spots.
  • 24. Nevus Of Ito • U/L slate blue mottled , macular pigmentation. • Regions Supplied by posterior supraclavicular & lateral brachial cutaneous nerves (supraclavicular, scapular & deltoid regions)
  • 25. Microscopy: Hyperpigmentation of epidermis Bipolar melanocytes dispersed singly in superficial dermis
  • 26. Blue Nevus • Benign, localized pigmented lesions. • On skin 3 types –  Common blue nevus  Cellular blue nevus  Combined nevus • Childhood – extremities & scalp • Histologically common feature - Presence of dendritic melanocytes in reticular dermis associated with variably stromal fibrotic response.
  • 27. Common Blue Nevus • (<10 mm) bluish-grey well circumscribed dome shaped papule. • Near dorsa of the hands & feet , scalp. • Microscopy:  Normal epidermis.  Pigmented spindle and dendritic melanocytes in a focal area of the reticular dermis, associated with thickened collagen bundles.
  • 28.  typically larger and their density is much greater  Cells have plenty of melanin.  Melanophages are seen, but not numerous or dense.  Melanocytes - positive for S-100, HMB-45 & Melan- A. • D/D – Dermatofibroma ( If minimally pigmented)
  • 29. Cellular Blue Nevus • blue nodule,1 to 3 cm in diameter. • buttocks or in the sacrococcygeal region. • Microscopy: • bulky, heavily pigmented cellular tumor . • spanning the reticular dermis. • Extend into the subcutis forming a bulbous expansion ( Dumb Bell Pattern).
  • 30. • comprising of deeply pigmented dendritic melanocytes + cellular islands large spindle shaped or epitheloid cells with ovoid nuclei and abundant pale cytoplasm often containing little or no melanin. • Melanophages often seen. • Four histological subtypes: 1. Mixed biphasic 2. Alveolar 3. Fascicular or neuronevoid (monophasic spindle-cell type) 4. Atypical varieties
  • 31. Spindle cells lie in contiguity with one another, unlike the cells of common blue nevi, most of which are separated from one another by collagen bundles Mixed biphasic pattern , with ovoid islands of polygonal cells with somewhat clear cytoplasm alternating with spindle cells, the latter often pigmented.
  • 32. SPECTRUM OF HP FEATURES OF INTRADERMAL MELANOCYTIC PROLIFERATIONS MELANO- CYTOSES COMMON BLUE NEVUS CELLULAR BLUE NEVUS COMBINED NEVUS Paucicellular, Interstitial proliferation of bland Dendritic melanocytes sclerotic stroma + heavily pigmented lesion larger, deeper +Oval melanocytes with abundant cytoplasm with little or no melanin MF+ blue nevus with an overlying melanocytic nevus or to other combinations of benign nevi
  • 33. Arising From Nevus Cell - Melanocytic Nevus CONGENITAL ACQUIRED • Junctional • Compound • Intradermal SPECIAL VARIANTS • Spitz • Dysplastic • Halo • Deep Penetrating • Recurrent • Pigmented Spindle Cell Tumor Of Reed • Balloon Cell
  • 34. • Benign non neoplastic proliferation of melanocytes • Pigmented or nonpigmented lesions ,< 5 mm in diameter. • Adolescence or early adulthood, rarely at birth. • Cells arranged in cohesive nests with relative uniformity of the nevus cells and fairly regular spacing of the nests. • Nests located at the tips of the rete ridges (for junctional and compound nevi)
  • 35. CONGENITAL NEVI • Found in 1% of newborn. • Usually solitary – trunk , lower extremities and scalp • larger than acquired nevi measuring >1.5 cms. • Giant congenital nevi,(garment nevi)- > 20 cms • Giant congenital melanocytic nevi – increase risk of the development of melanoma.
  • 36. • Microscopy:  May be junctional, compound or intradermal  Presence of melanocytes around and with in the adenxae ,nerves , vessel wall.  Nevus cells extend between collagen fibers singly or in a Indian file pattern- characteristic feature. nevus is very broad and deep- epidermis-dermis-fat spindle shaped heavily pigmented
  • 37. ACQUIRED NEVI • More prevalent in boys, more in fair skin and blond or red hair. • Undergo progressive maturation with increasing age of the lesion. • The lesion become stable after growing to some size and may even involute. With advancing age there is progressive decrease in the number of nevi Histopathological types Clinical types Junctional Flat macules Compound Pappilomatous Intradermal Dome shaped, pedunculated lesion
  • 38. Junctional Nevus • Well circumscribed brown to black macules, any where • childhood or early adolescence • Microscopy:  Presence of well circumscribed nests of cohesive melanocytes either within lower epidermis or bulging into dermis.(theque)  Originating from tips and sides of rete ridges.
  • 39. • Variable lentiginous melanocytic hyperplasia. • No continuous proliferation of melanocytes in the suprapapillary regions of the epidermis between the rete ridges. • Melanophages in dermis • D/D – 1. Lentigo simplex - no theques 2. Junctional lentiginous melanocytic nevus- not circumscribed
  • 40. Compound Nevus • Elevated pigmented papule. • Microscopy:  Junctional melanocytic theques + dermal population of melanocytes (Nevus cell nests are present in the epidermis as well as appearing to ‘drop off’ into the dermis).  Periadenexal & adventitial dermis spared Compound nevus: both junctional and dermal nests of nevus cells
  • 41. • The nevus cells change their morphology as they go deeper into the dermis. Three morphologic subtypes of nevus cells are recognized, from superficial to deep: TYPE LOCATION SHAPE MELANIN A (epithelioid) upper dermis Round to polygonal with abundant cytoplasm variable B (lymphocytoid) mid-dermis same but smaller than type A less than A C lower dermis elongated spindle shaped ( fibroblast) rarely contain
  • 42. INTRADERMAL NEVUS • Adults, dome shaped lesions flesh coloured • Microscopy:  Upper dermis -  nests and cords of nevus cells concentrated around pilosebaceous units.  Multinucleated nevus cells - small nuclei in a rosette-like arrangement or close together in the center of the cell.
  • 43.  Lower dermis –  Less cellular c/o spindly cells, similar to that of the fibers in a neurofibroma(neurotized nevus).  In other areas, the nevus cells lie within concentrically arranged structure , resemble Meissner's tactile bodies.  Clefts - between some nests of nevus cells and the surrounding epidermis as well as stroma, simulates a lymphatic space and mimics lymphatic invasion cell nests having a neuroid differentiation
  • 45. BALLOON CELL NEVUS • Clinically indistinguishable from melanocytic nevi • Microscopy-  Epidermis - Balloon cells seen singly or in groups or absent .  Dermis - arranged in lobules of varying size admixed with ordinary nevus cells.  Large cells , small round centrally placed nucleus with empty , finely granular or vacuolated cytoplasm
  • 46.  Large vacuoles – Enlargement and coalescence of degenerating melanosomes.  Stains for lipid, glycogen and acid or neutral mucopolysaccharide – negative. D/D –  Large adipocyte in intradermal nevi – Flattened nucleus at periphery.  Clear cell hidrenoma – Presence of PAS positive glycogen & keratin.
  • 47. SPITZ NEVI (benign juvenile melanoma ) • Spindle &/or epitheloid cell nevus. • Children & young adults • Head & neck and extremities • Solitary dermal dome shaped small pink nodule • Majority – Compound , 20% intradermal, 5-10% junctional
  • 48. Microscopy • Small , symmetric, well circumscribed. • epidermis shows hyperplasia & elongated rete ridges . • Nevus cell - Spindle cells & Epitheloid cells • Arrayed as epidermal nests grouped in a vertical orientation (bunches of bananas or raining down pattern), with clefting artifact. • little or no pagetoid spread pattern.
  • 49. • Maturation of the cells with increasing depth. • Bizarre giant cells may be seen. • Presence within the epidermis of red globules, form large bodies through coalescence – Kamino Bodies , apoptotic degenerating melanocytes. • Little or no melanin. • At the dermal base - no mitoses • Lymphocytic infiltration in dermis
  • 50. • Variants: 1. Desmoplastic 2. Hyalinizing 3. Angiomatoid
  • 51. large cells, with abundant amphophilic cytoplasm, which may be spindled or polygonal in shape (large spindle and/or epithelioid melanocytes Maturation in a spitz nevus Globoid eosinophilic bodies (kamino bodies) PAS & TRICHOME +VE
  • 52. Diagnostic criteria : Major Criteria Minor Criteria • Symmetry • Cell type –large spindle and epithelioid cells • Maturation • Absence of pagetoid spread • Kamino bodies • Junctional cleavage • Superficial multinucleate nevus cells • Perivascular inflammation • No atypical mitoses • Solitary nevus cells in deeper parts
  • 53. • IHC :  react for HMB45, Melan A/MART1, NK1/C-3 and S100. Of importance is stratification seen with HMB45- deeper cells stain intensely than superficial cells, Stratification also seen with cyclin D1 • D/D –  Spitzoid melanoma- no maturation, atypical mitoses, pagetoid spread  Pigmented spindle cell nevus of reed- seen in blacks & is heavily pigmented  Pyogenic granuloma, mastocytoma, juvenile xanthogranuloma, warts, melanocytic nevi
  • 54. PIGMENTED SPINDLE CELL NEVUS • 3-6 mm , deeply pigmented , flat or slightly raised papules. • Young adult, female,- lower extremities. • Microscopy:  Symmetrical - proliferation of elongated spindle shaped heavily pigmented melanocytes in nests at the dermo- epidermal junctions.  Vertically oriented & blend with adjacent keratinocytes rather than forming clefts as in spitz nevi.  Characteristic accumulation of melanophages.  Base of the lesion – superficial reticular dermis, show lymphocytic response. Kamino bodies may be seen in epidermal compartment
  • 55. D/D-  Melanoma of the superficial spreading type Pigmented spindle shaped nevus Melonoma ( Superficial spreading) • Small , symmetric , sharply demarcated lateral margins. • Cells Uniform from side to side • Descend into the dermis and mature along nevus line. •Abnormal mitosis in uncommon • Large , asymmetric with lateral extension. • Cellular variabilty. • Little or no maturation • Common
  • 56. Deep Penetrating Nevus (Plexiform Spindle Cell Nevus) • 2nd and 3rd decades • Head, neck and shoulder • 2- 9 mm, darkly pigmented papules and nodules. • Microscopy –  Compound type  Circumscribed and pyramidal in shape with a broad base abutting the epidermis and apex towards the subcutaneous fat. Composed of loosely arranged nests or plexiform fascicles of large pigmented spindle and epithelioid cells interspersed with melanophages
  • 57. • Slight nuclear pleomorphism but inconspicuous nucleoli • Mitoses absent. • D/D – Melanoma- Marked atypia Pagetoid spread Irregular acanthosis & thinning
  • 58. HALO NEVUS • Sutton's nevus or nevus depigmentosa centrifugum • Pigmented macule surrounded by a depigmented zone or halo. • children & young adults, Back. • Almost any of the types. • Pathogenesis :  Circulating Abs against neoplastic melanocytes & inflammatory cells in the lesion( T lymphocytes both Ag presenting and cytotoxic)  The halo - due to cross reaction between a field of melanocytes and the T cells.
  • 59. Microscopy: • Common – Inflammatory halo nevus. • Early - nests of nevus cells embedded in a dense inflammatory infiltrate in the upper dermis and at the dermoepidermal jn. • Later - scattered nevus cells tend to predominate over nests. apoptotic cells also seen. • Inflammatory infiltrate -lymphocytes and few melanophages. • The region of halo nevus at first shows reduction in the number of melanocytes and later their complete absence At the periphery of the nevus, the halo is a region where pigment and melanocytes are reduced or absent, and there may be a subtle lymphocytic infiltrate at the dermal-epidermal junction
  • 60. Types Inflammation Involution Halo Inflammatory Present Present Present Non inflammatory Absent Absent Present Halo nevus phenomenon Present May involute Absent Halo dermatitis around nevus ( Mayerson’s eczematous nevus) Temporary reaction surrounding a nevus Present
  • 61. Recurrent Nevus (Pseudomelanoma) • A nevus may recur following an incomplete excision presenting clinically as hyperpigmented lesions • Confined to the region of the scar and typically presents with in weeks of the surgical procedure. • Microscopy:  Lentiginous and junctional theques above the dermal scar.  No epidermal ridges.  Dermal fibrosis.  Nevus cells are present in the deep dermis and at the edge of the scar.
  • 62. • HMB45 stains more prominently in the recurrent nevi than the original lesion. • D/D – RECURRENT MELANOMA -  Sharp circumscription of the intraepidermal component,  Presence of melanocytes in nests and as single units mostly at the junction and the typical nevoid cells of the preexisting dermal melanocytic nevus beneath a scar are helpful clues
  • 63. Dysplastic Nevus • present as macules often with a central papule, have irregular border and irregular pigmentation > 5 cms. • Multiple or solitary • Adults • Trunk , lower legs ( Females) • Shows cytological and architectural atypia & regarded as intermediate b/w common nevi and superficial spreading melanoma
  • 64. Junctional / compound nevi Architectural Abnormality- • Shoulder phenomenon • stromal response with fibrosis.(includes lamellar and concentric fibroplasias) • Lentiginous proliferation of melanocytes – not contiguous nevus cells- spindle / epitheloid • Random cytological atypia in epidermal component- large pleomorphic nuclei. Single & nested melanocytes , lamellar fibroplasia Cytologic atypia
  • 65. D/D – Radial growth phase melanoma
  • 66. References • Levers histopathology of skin • Weedons pathology • Mckee • Sternberg

Editor's Notes

  1. Lentiginous proliferation tem used for basal proliferation of melanocytes as single cells rather than nest with typically but not always elongation of rete ridges.
  2. Microscopically it shows lentiginous proliferation that means…
  3. Non contiguous means cell bodies are separated from one another by keratinocytes. Contiguous means cell bodies at least focally touches each other. In lentigo simplex though there is elongated rete ridges but melanocytes more obviously increased and lie in contiguity. Lentigo maligna shows flattening or absence of rete ridges with continuous proliferation & cytological atypia.
  4. In lentigo simplex focally lie in contiguity with one another around the tips m side but not between the rete.
  5. Increase in melanin pigment due to increase in the melanocytes within the dermis.
  6. Most of them are filled with numerous fine granules of melanin, often so completely that their nuclei cannot be visualized. the melanocytes have a similar appearance to those seen in the Mongolian spot and in the nevus of Ota, but they are typically larger and their density is much greater The melanophages differ from the melanocytes by being shorter and thicker, by showing no dendritic processes, and by containing larger granules. In contrast to the melanocytes, the melanophages are DOPA negative. (B) Spindle-shaped or dendritic melanocytes are placed among reticular dermis collagen bundles, which are often, as here, slightly thickened (C) Unlike the cells of most common or congenital nevi that involve the reticular dermis, the cells of blue nevi are usually heavily pigmented, with coarsely divided melanin granules. (D) Especially at the periphery of the lesion, the cells are arranged as single cells placed among collagen bundles, rather than sheets or fascicles.
  7. often distinctive at scanning magnification. . In lesions that enter the subcutis there is often a cellular nodule at the base, connected to the overlying tumor in a “dumbbell” pattern.
  8. In the common mixed-biphasic type, there are clusters of epithelioid cells with somewhat clear cytoplasm, between which there are fascicles of spindle cells . Lesions termed atypical blue nevi - rare but distinct variant of cellular blue nevi, characterized by unusual features including architectural atypia (infiltrative margin and/or asymmetry) and/or cytologic atypia .
  9. Giant nevus- Focal areas of increased pigmenation some times associated with nodularity. They are deeply pigmented and covered with moderated growth of hairs.
  10. Involvement of eccrine glands and septa is an important feature of a true congenital nevus.
  11. it should be realized that these are transitional stages in the life cycle of nevi, which are believed to start out as junctional nevi and, after having become intradermal nevi, undergo involution.
  12. But still in contact with epidermis.perhaps in the process of dropping off to form compound nevus.
  13. In the epidermis, single cells and nests of nevi are arranged near the dermal-epidermal junction near the tips and sides of elongated rete ridges (a lentiginous pattern). There is minimal or no atypia.
  14. Histologically, a compound nevus possesses features of both a junctional and an intradermal nevus.
  15. These giant cells are different from cells that is found in spitz nevus tose are bizarre.
  16. Color is pink because of scarcity of melanin and in some lesions associated vascularization. Therefore it is often diagnosed clinically as pyogenic granuloma , an angioma or a dermal nevus.
  17. In term of their architecture pattern they resemble common nevi. Occasional hyperplasia of epidermis is so florid to be termed as pseudoepitheliomatosis, give a confusion with SCC especially in superficial biopsies. Cleftng artifact at the perimetry. Spindle cells or epitheloid cells may predominate or the two types ma intermingled. Apart from the cell bodies these cells in any given spitz nevus resemble in their nuclear and cytoplasmic features.
  18. As they mature become smaller and look like a cell of a commmon nevus. Giant cells also seen in melanoma but difference being spitz nevi giant cells have regular nuclei of same size. Kamino bodies a useful but not pathognomic cytological criterion for spitz nevi also seen in 2% cases of melanoma and 0.9 % of ordinary nevi.
  19. Due to its sudden appearance a diagnosis of melanoma is usually suspected clinically. Configuration is typical of a plaque where breadth is more than the height. And the lesional cells are typical junctional or confined to epidermis and papillary dermis. Unlike those of spitz nevus Cells are narrow elongated spindle cells without epithelioid cells, and they contain abundant, usually coarse melanin pigment. some (usually slight) degree of pagetoid melanocytosis is not unexpected. Mitoses may be numerous in the epidermis, but the lesional cells in the dermis tend to be mature, with few if any mitoses. Clefting artifact between the nests and the adjacent keratinocytes tends to be less prominent than in Spitz nevi, but may be present, as seen here.
  20. (B) A dense infiltrative lymphocytic response blurs the silhouette of the lesional nevus cells in the dermis at scanning magnification. (C) Small lymphocytes are diffusely placed among the dermal nevus cells, which may appear swollen and slightly atypical (reactive atypia).
  21. Halo dermitis refers to temporary inflammatory reaction around a nevus.
  22. The pigmentation is confined to scar.
  23. residual dermal nevus cells of the persistent original nevus are present to the right of the scar and beneath it. (B) The cells of the recurrent nevus in the epidermis are variably enlarged, and they may be arranged with single cells predominating in foci and extending up into the epidermis in a pagetoid pattern
  24. 'shoulder phenomenon' characterized by  peripheral extension of the junctional component, beyond the  dermal component. The stroma around the rete ridges appear more condensed and eosinophilic than the collagenous stroma in the papillary dermis