Transcript Document

Melanocytic Nevi and Neoplasms
Andrew’s chapter 30
JoAnne M. LaRow, D.O.
Epidermal Melanocytic Lesions
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Normal melanocte occurring at the epidermaldermal junction is a dendritic secretory cell
supplying all normal melanin to skin
These cells contain pigment granules
(melanosomes)
Stain with dopa reaction and silver stains
Melanocytes of the epidermis transfer the
melanosomes through their thin dendritic
processes into surrounding keratinocytes
Size and number in keratinocytes determine
pigmentation of skin and hair
Nevus Spilus
Pigmented, light brown or
tan macule, varied
diameter, speckled with
smaller, darker-colored
macules or papules
Lower extremity & trunk
frequently
May be <1cm or large
May follow a dermatomal
distribution when large
Usually they do not cross the
midline
When these nevi follow a
dermatomal distribution they
may be referred to as a
zosteriform, or sometimes a
speckled lentiginous nevus
When nevus spilus is present with
a nevus flammeus =
phakomatosis
pigmentovascularis
phakomatosis
pigmentokeratotica= a
syndrome of organoid nevus
with sebaceous differentiation,
hemiatrophy with muscular
weakness & other neurologic
findings & speckled
lentiginous nevus
Nevus Spilus
Nevus Spilus
-The darker speckles usually contain nevus
cells
-Due to this melanoma may arise in the with
greater frequency than in normal skin
-However, removal is not necessary
-Removal by Q-switched ruby laser has been
reported effective
Lentigo Simplex
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Usually arise in childhood but can arise anytime
Sharply defined, rounded, brown or black macules
found anywhere on body or mucosa
Histologically shows elongation of rete ridges,
increase in number of melanocytes in basal layer,
increase of melanin in both melanocytes, and basal
keratinocytes, and melanophages in the upper
dermis
No therapy is needed/ there is no predisposition to
neoplastic change
Solar Lentigines
Commonly called “liver
spots”
Hyperpigmented macules
May evolve into sk’s or
lichenoid keratoses
Tx=liquid nitrogen, laser
May recur, as a lentigo
maligna or lentigo
maligna melanoma
Be aware-oral methoxsalen
photochemotherapy or
frequent tanning salons
may develop lentigines on
non-sun-exposed areas
and these may show
cellular atypia
Penile and Vulvar Melanosis
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Localized pigmentary
alterations
Most often show basilar
hyperpigmentation
May appear in large
patches or in smaller,
well-demarcated lesions
Present on the penis or in
women on the labia
majora
Bannayan-Riley-Ruvalcaba
Syndrome
Rare, AD disorder that manifests in
childhood
 80% of the pts are male
 Characterized by genital lentiginosis,
macrocephaly, motor and speech delay,
mental retardation, lipomas, hemangiomas,
verruca vulgaris, and many types of facial
papules
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Multiple Lentigenes Syndrome
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Lentigines are dark
brown macules 1-5
mm.
Preponderance on the
trunk
Multiple generalized
lentigines may occur
with a number of
associated signs as an
dominantly inherited
syndrome
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LEOPARD Syndrome
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Leopard syndrome =
acronym for lentigines,
electrocardiographic
abnormalities, ocular
hypertelorism, pulmonary
stenosis, abnormalities of
genitalia, retardation of
growth, and deafness
Moynahan Syndrome
Multiple lentigines
 Congenital mitral stenosis
 Dwarfism
 Genital hypoplasia
 Mental deficiency
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Centrofacial Lentiginosis
Characterized by lentigines on the nose, and
adjacent cheeks
 Sometimes associated with status
dysraphicus, multiple skeletal anomalies,
and CNS disorders
 Spares the mucous membranes
 Onset is first years of life
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Inherited Patterned Lentiginosis
in Blacks
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AD- reportedly, 10 lightcomplexioned black
patients who developed
numerous lentigines in
infancy or early childhood
Distribution is central
face, lips, with variable
involvement of dorsal
hands and feet, elbows,
and buttocks
Sparing of mucous
membranes and no
internal abnormalities
Carney’s Syndrome
AKA NAME syndrome or LAMB
syndrome
 Characterized by cardiocutaneous
myxomas, lentigines, blue nevi, and
endocrine anomalies
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Peutz-Jeghers Syndrome
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AD
Pigmented macules on
the lips, oral mucosa,
perioral acral areas
Gastrointestinal
polyps, especially
prominent in the
jejunum are seen
Melanoacanthoma
uncommon lesion, a benign epidermal
melanocytic neoplasm, occurring on the
head
 Resembles a pigmented sk or a pigmented
BCC
 Predominantly seen in white men > 60 yrs
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Cellular Nevi
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Begins to appear in first yrs of life, increase in
prevalence and number over the next two decades,
after which there is a steady decline
Females tent to have more than males
Less common in sun-protected areas
Maximum number is at age 20- 25 yrs, the average
number is 40
Sun exposure increases the number of nevi in the
exposed skin
Eruptive nevi are rare, but may occur after severe
bullous disease such as TEN, EM, or severe
sunburn, Addison’s disease or immunosuppresion
Junctional Nevi
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Nevi begin as small, flat,
pigmented macules =
junctional nevi
A smooth, hairless, light
to dark brown macule,
varying in size from 1 –6
mm
Occurs on any site,
especially on palms,
soles, scrotum
During adolescence some
will become compound or
intradermal
It is characterized by
single melanocytes, or
theques of them in the
lower epidermis
Compound Nevus
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The compound nevus is one that is still
manifesting so-called junctional activity(
accumulation of melanocytes in theques in
the epidermis) but has formed structure of a
cellular nevus in the dermis as well
Junctional Nevi
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Nevi begin as small, flat,
pigmented macules =
junctional nevi
A smooth, hairless, light
to dark brown macule,
varying in size from 1 –6
mm
Occurs on any site,
especially on palms,
soles, scrotum
During adolescence some
will become compound or
intradermal
It is characterized by
single melanocytes, or
theques of them in the
lower epidermis
Compound Nevus
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The compound nevus is one that is still
manifesting so-called junctional activity(
accumulation of melanocytes in theques in
the epidermis) but has formed structure of a
cellular nevus in the dermis as well
Compound Nevus
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An 8-mm, wellcircumscribed,
symmetric, uniformly
colored papule
A lesion of this size
could be an acquired
nevus or a small
congenital pattern
nevus
Compound Nevus
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Nests of
nevus
cells in
the
epidermi
s
overlying
a dermal
compone
nt of
orderly
nevus
cells
Compound Nevus
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Acral type-thickened basket
weave stratum corneum
shows that it is an acral site
Nevus is small and
symmetric, and shows both
a junctional and superficial
dermal component
The nests in the papillary
dermis are small, orderly,
and lack atypia. The
epidermal component may
show a few pagetoid cells
Intradermal Nevus
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a compound nevus in which junctional
activity- that is, theques of melanoctyes in
the epidermis or at the dermal epidermal
junction- has ceased, and all the nevus cells
are in the dermis
Intradermal Nevus
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Low power-as in
junctional nevi , dermal
nevi contain nevus cells
that are recognized at this
power by tendency to be
arranged in nests
High power- at the base of
this dermal nevus the
melanocytic cells
resemble neural
structures( neurotization)
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A pigmented nevus, varying
in size from 1 –5 mm, usually
occurring on the head, neck,
and trunk.
They are clinically
indistinguishable from
ordinary pigmented or
nonpigmented nevus
Histologically, the lesions are
composed of peculiar
vesicular cells that appear to
be foamy and form large pale
polyhedral balloon cells that
may be multinucleated giant
cells in addition to nevus
cells.
Not considered potentially
malignant, and treatment is
same as other nevi
Balloon Cell Nevus
Halo Nevus
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AKA Sutton’s nevus,
perinevoid vitilgo, &
leukoderma acquisitum
centrifugum
A pigmented nevus with
surrounding depigmented
zone
Nevus is usually compound
or intradermal
May be single or multiple
Usually on the trunk
Mostly develop in teenagers
No tx indicated- central
nevus disappears with time
leukodermic area will
usually repigment with time
Halo Nevus
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The nevus architecture
is obscured by a dense
lymphocytic infiltrate
Lymphocytes infiltrate
among the dermal
nevus cells, which
eventually degenerate
and disappear
Congenital Nevocytic Nevus
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Giant Pigmented Nevus
(Giant hairy nevus,
bathing trunk nevus)
Characterized by a large,
darkly pigmented hairy
patch in which smaller,
darker patches are
interspersed or present as
small satellite lesions
Skin may be thickened or
verrucous
Has a tendency to follow
a dermatome distribution
Trunk favored site
Congenital Nevocytic Nevus
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Giant hairy nevi are
present at birth and grow
proportionally to the site
of the body where they are
located
By definition they are
>20cm
When a large congenital
nevus involves the axial
skin, there may be an
associated neurocutaneous
melanocytosis
Incidence of melanoma
developing is 3% to 7%
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About 40% of the malignant
melanomas seen in children
occur in large congenital nevi
-risk is greatest for axial
lesions
If neurocutaneous melanosis
is present (which can be
detected by MRI), the risk of
dying at a young age is high
secondary to hydrocephalus or
leptomeningeal melanoma
Most recommend total
surgical excision and
resurfacing autografts
Alternative treatmentsdermabrasion, curettage, and
laser ablation- are designed to
eliminate some of the nevus
cells, with theoretic lowering
CNN
Small and Medium-sized
Congenital Nevocytic Nevus
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Small - < 1.5 cm in greatest diameter
Medium- > 1.5 cm but < 20 cm
Found in 1% of newborns
Half eventually become hairy
Data to determine the incidence of melanoma are
still being gathered
Excision is recommended for lesions of the hairy
scalp, or those of great cosmetic concern or nevi
with unusual clinical features
Epitheliod and Spindle-Cell
Nevus(benign Juvenile
Melanoma, Spitz Nevus)
Spitz Nevus
A smooth-surfaced, raised, round, slightly
scaly, firm papule with distinctive pink,
brownish red, or purplish red color
 Typically, firm,rosy papule on the face,
especially on the cheek
 3 – 10 mm in diameter
 Female predominance
 Should be completely excised
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Spitz Nevus
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A variant of the compound
nevus
Epidermal irregular
acanthosis,
pseudoepitheliomatous
hyperplasia, and thinning
of the epidermis
Nevus cells are
pleomorphic, but mostly
spindle-shaped (fusiform),
or polygonal (epithelioid)
cells
Spitz Nevus
Giant cells with eosiophilic
cytoplasm and a large
nucleus may be seen
 Multinucleated giant cells
are seen less frequently
 No difference between
childhood and adult
lesions
 Eosinophilic globules with
fibrillar microstructure
(Kamino bodies) are
found in 60% - 85% of SN
 May also be present in
melanomas (12&) and
compound nevi(8%), but
are fewer and smaller in
SN
Spitz Nevus
* Immunohistochemical staining for MIB-1
and bcl-2 will distinguish most Spitz nevi
from melanoma;melanomas are
immunoreactive, whereas Spitz nevi are not
* Differential diagnosis-pyogenic granuloma,
mastocytoma, juvenile xanthogranuloma, or
melanoma
Dysplastic Nevus
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Variegated tan, brown,
pink coloration
Pink hues seen in macular
portion
Macular portion always
present, may comprise
entire lesion, but
frequently surrounds a
papular center
Generally larger than are
common nevi, usually 5 –
12mm, with irregular
borders
Dysplastic Nevus Syndrome
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Around 1978 Lynch et al recognized an autosomal
dominant inheritance pattern in families with
unusual nevi and multiple melanomas-initially
described by Clark et al as B-K mole syndromethen named familial atypical multiple molemelanoma syndrome
Now termed dysplastic nevus syndrome (DNS)
Pts with dysplastic nevi send at least two blood
relatives with dysplastic nevi and melanoma have
the worst prognosis with possibly 100% lifetime
risk of melanoma
Dysplastic Nevus SyndromeGenetics
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25% -33% of pts have germline mutations on
chromosome 9p in the CDKN2A tumorsuppressor gene-which encodes for an inhibitor of
a cyclindependent kinase 4 (CDK4) that functions
to suppress proliferation
In these pts with mutations that impair the
function of the p16 suppressor protein, referred to
as the p16M alleles, there is a concomitant
predisposition to pancreatic cancer
Dysplastic Nevus Syndrome
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Dysplasic nevi occur commonly in pts without a
personal or family history of melanoma-5% -20%
of pts having at least one clinically dysplastic
nevus
This is important for (1) histologic evaluation is
neede (2) a careful history and evaluation of
family members (3) they provide another risk
factor for melanoma predisposition
Dysplastic Nevus Syndrome
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Histologic features as per an NIH consensusbasilar melanocytic hyperplasia with elongation of
rete ridges; spindle-shaped or occasionally,
epithelioid melanocytes arranged horizontally and
aggregating in nests that fuse with adjacent rete
ridges; lamellar and concentric superficial dermal
infiltrate; cytologic atypia, usually present but not
essential for diagnosis
Dysplastic Nevi
Patients with dysplastic nevi and a positive
family or personal history of melanoma,
physician examination every 3 – 6 months
 Excision of those nevi that change clinically
 Photographs with measured scale is useful
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Melanoma
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Originate from
melanocytes at epidermaldermal junction
Half will develop in
preexisting nevi
Prolonged, non invasive,
horizontally oriented
growth phase
When tumor nodule
develops the vertical
growth phase is occurring
and the risk of metastatic
disease increases
dramatically
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One in 80 Americans will
develop melanoma
Incidence is low until after
puberty
Children may present with
congenital melanoma or
acquired melanoma
Congenital melanoma may
occur because of
transplacental
transmission, as a primary
intrauterine lesion, as a
melanoma from a
congenital nevus in utero,
or as prenatal metastatic
lesions from
neurocutaneous melanosis
all of these have a poor
prognosis
Melanoma
Diagnosis of Melanoma
- surgical excision is the best method
-for larger lesions an incisional or punch biopsy,
deep enough is considered good practice
-when melanoma is suspected in a melanotic freckle
or a giant pigmented nevus, biopsy should be done
through the thickest and most atypical area and
multiply sectioned to find thickest area of
involvement
Histologic diagnosis:
-presence of mitoses
-inflammatory reaction
composed of
lymphocytes and
possibly plasma cells
-dermoepidermal
junctional activity
-absence of dermal
stroma
Histologic diagnosis:
-a moderately brisk tumorinfiltrating lymphocyte
response is present around
the nodule
- the cells in the nodule are
large epithelioid
melanoma cells that have
abundant cytoplasm and
large irregular nuclei with
prominent nucleoli with
numerous mitoses
Melanoma
Metastasis-usually
manifested by
pigmented nodules
appearing around the
site of the excision
Early remote metastases
occur via lymphatics
and regional
lynphadenopathy may
be the first sign
Melanoma
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> 50 benign nevi
Presence of large congenital nevus
Presence of clinically dysplasic nevus
Mutations in the p16-CDK4
Immunodefiency syndromes-acquired or genetic
PUVA treatments
Xeroderma pigmentosum
Use of tanning lamps
Levodopa therapy for Parkinson’s disease has
been implicated in 19 case reports by Rampen
Melanoma
There are four recognized clinicohistologic
types:
1.) Lentigo maligna (melanoma in situ,
noninvasive melanoma)
2.) Superficially spreading melanoma
3.) Acral-lentiginous melanoma
4.) Nodular melanoma
Melanoma
*Pedunculated, polypoidal melanomas,
inflammatory melanomas, amelanotic
melanomas, and hyperkeratotic and
verrucous melanomas are clinical findings
*At a microscopic level-desmoplastic,
neurotropic, myxoid, balloon cell, and
signet cell patterns are seen
Lentigo maligna(melanoma in
situ, noninvasive melanoma)
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Begins as a tan macule that extends peripherally,
with gradual uneven darkening, over several years
After a radial growth of 5 to 20 years, vertically
growing melanoma usually develops within it
A palpable nodule within the original macule is the
best evidence that a lentigo maligna melanoma has
occurred
Equal incidence in men and women
Usually 60-70 yrs
Usually on chronically sun-damaged skin, most
often on the face
Accounts for 5% of all melanomas
Lentigo maligna(melanoma in
situ, noninvasive melanoma)
Superficially spreading
melanoma
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In a study by Bolognia et
al 5% of lesions with an
eccentric foci of
hyperpigmentation(a
roundish area of brown or
black 3mm or< and
located peripherally) are
melanomas arising from
within a nevus
It is necessary to ensure
that the pathologist
sections through the black
dot to make this early
diagnosis
Acral-lentiginous melanoma
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Acral-lentiginous melanoma lies midway between
the lentigo maligna and the superficially spreading
melanoma in respect to speed of horizontal growth
into adjacent epidermis
Subungual and mucosal lesions are in this
category
Account for 10% of all melanomas
The most common type among Japanese, African
American, Hispanics, and Native Americans
Median age is 50 yrs with equal sex distribution
Melanoma- workup and followup
-establish a family history
-thorough review of systems
- physical exam
- A consensus conference in 1992 concluded that a
staging workup was not indicated for melanomas
below 1.0 mm thickness
- Many physicians obtain a CXR and an LDH
- As in the initial workup, more information and a
consensus statement would help to establish
indications for testing
- Consultation with an oncologist is worthwhile
Melanoma-treatment
-early diagnosis and excision
-margin of 0.5 to 1.0 cm for melanoma in situ
-1.0 cm margin for melanomas < 2.0 cm thick
-3.0 cm margin for those thicker than 2.0 mm
-Zitelli et al recommended wider margins for
melanomas of the head, neck, hands, and feetthey recommend a minimum surgical margin of
1.5 cm, unless Mohs’ micrographic surgery is use
- ELND is controversial and therefore intraoperative
lymphatic mapping is used
Melanoma-treatment
-high-dose interferon alfa-2b therapy has been used,
however efficacy is equivocal and toxicity high
-adjuvant interferon alfa-2a treatment has been
reported to diminish the occurrence of mets and
prolong disease free survival in pts with
melanoma > 1.5 mm thick
-chemotherapy is not effective
-Adoptive immunotherapy with lymphokineactivated killer cells + interleukin-2, or high –dose
into leukin-2 alone is also toxic, some patients are
responsive
-perfusion chemotherapy has been used for extremity
melanoma and has almost eliminated the need for
amputation
Dermal Melanocytic Lesions
At birth, melanocytes may be present in the
dermal portion of the skin of the scalp, the
backs of the hands, and the sacrum
 These are large ameboid cells that normally
disappear shortly after birth
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Mongolian Spot
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Bluish gray macule of
varying size from 2-8 cm
Occurs typically in the
sacral area of the newborn
80-90% of Asians,
Southern Europeans,
American blacks, and
Native Americans
Multiple spots may be
situated in other locations
Mongolian Spot
Multiple spots occurring in a widespread
distribution have been termed generalized
dermal melanocytosis or dermal
melanocytic hamartomas
If associated with a nevus flammeusphakomatosis pigmentovascularis
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Aka nevus fuscocerulleus
opthalmaomaxillaris
Usually present at birth ,
especially if the patient is going
to have ocular involvement
May have involvement of the
conjunctiva and the skin about
the eye
On the skin brown, slate gray,
or blue-black macules grow
slowly larger and deeper in
color
80% occur in women; 5% are
bilateral
Usually a benign lesion
malignant melanoma may occur
Most common location is the
choroid
Glaucoma may occur
Nevus of Ota
Nevus of Ito
Aka nevus fuscoceruleus acromiodeltoideus
 Has the same features as nevus of Ota
except that it occurs in the distribution of
the posterior supraclavicular and lateral
cutaneous brachial nerves
 It involves the shoulder, side of the neck,
and supraclavicular areas
 Tx –Q-switched ruby laser are dramatic
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Blue Nevus
Two types:
 1.) Blue nevus of Jadassohn-Tiche
(common blue nevus)
 2.) Cellular blue nevus
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Within the dermis there is
a poorly defined but
symmetric spindle cell
proliferation that is dark
brown in color
No significant change in
the overlying dermis
The spindled heavily
pigmented cells encircle
collagen bundles in the
reticular dermis, a pattern
also seen in
dermatofibromas
The lesion is composed of
elongate cells that are
heavily pigmented and
show prominent
pigmented dendrites
Blue Nevus
Blue Nevus of Jadassohn-Tiche
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The typical common blue
nevus or nevus ceruleus
Steel-blue nodule that
begins early in life
Slow growing
Rarely reaches 2-10mm
Occurs most frequently on
the dorsal hands, feet,
forearms, shins, face, and
the buttocks
Cellular Blue Nevus
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Large, firm, blue or blueblack nodule
Frequently seen on the
buttock and sacrococcygeal
region
Occasionally present at birth
Seen in women 2.5 times as
frequently as men
Average age is 40
Uncommonly these invade
underlying structure such as
the skull in scalp lesions
Cellular Blue Nevus
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Frequently large and
involve a good part of the
dermis and extending
deeply as tonguelike
aggregates of tumor cells
at the base of the lesion
Involvement of the
subcutaneous fat is
common and does not
imply a malignant
diagnosis
Cellular Blue Nevus
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The cellular areas are
composed of uniform
spindled melanocytic cells
with mor cytoplasm and
larger nuclei than what is
seen in common blue
nevus.
There are irregularly
distributed collections of
course melanin pigment
within the cells
Epithelioid Blue Nevus
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Newly described lesion
Strong association with Carney’s complex
(myxomas, spotty skin pigmentation, endocrine
over activity, and schwannomas)
Occur frequently on the head and neck, and are at
times multiple
They are darkly pigmented, domed, and less than
1 cm
Malignant Blue Nevus
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-Cellular blue nevus may rarely undergo
malignant transformation into malignant
melanoma
-clinically increase in size, suddenly and
ulceration
-histologically, pleomorphism of nuclei, mitotic
figures, and invasion of clusters of malignant cells
into the deep dermis and fatty tissue
-excision has been mainstay of treatment
-Q-switched ruby laser has been reported to be
successful
- treatment of the malignant variety is the same as
MM