DERMATOPATHOLOGY
PREPARED BY: MARK JAYSON BARCELONA
Cell types and structure in the skin
Squamous
Serves to create a
epithelial cell
tough, durable
production
ofof the first line
Serves
as
one
physical barriera
Melanocyte
melanin
of
defense
stimulated
by
Secretes
cytokines
Dendritic cell
Constantly
exposed
to
absorbs and
Referred
to
as
neural
dendritic
cell
and defensins
microbial
and
non micro agent
Lymphocyte
protect
against
end
organ
Mediate the dendritic cell
Intraepidermal
UV radiationfor
Responsible
Afferent nerve
microscopic
pattern
Langerhan cell
fiber
physical
sensation:
and
clinical
expression
Sweat glands
pain,
touch , vibration
Adnexal
cutaneous
Hairoffollicles
itchiness,
coldand
and cells
components
Harboring
inflammatory
epithelial
stem
heat.
Maybe
disrupted
by trauma, burns etc.
infectious
disease
Nomenclature of skin lesion
Disorder of pigmentation and melanocyte
1. FRECKLES (ephiles)
Most common pigmented lesion of
childhood and lightly pigmented
individual
1 to several mm in diameter
Tan-red or light brown macules that
appear after sun exposure
Fade and darken in a cyclic
fashion during winter and
summer
Hyperpigmentation results
from increase amount of
melanin pigment within the
basal keratinocyte
2. Lentigo
Refers to a common benign
localized hyperplasia of melanocyte.
occurring at all ages, but often
initiated in infancy and childhood
The pathogenesis is unknown
May involve mucous membranes as
well as the skin
Consist of small (5 to 10 mm
across) oval, tan-brown macules or
patches.
Do not darken when exposed to
sunlight
histologic feature is linear (nonnested)
melanocytic hyperplasia
Elongation and thinning of the rete ridges are also
commonly seen in a lentigo.
Melanocytic Nevus (Pigmented Nevus, Mole)
common benign neoplasms caused in most
cases by acquired activating mutations in
components of the Ras signaling pathway.
Acquired melanocytic nevi are the most
common type and are found in virtually all
individuals.
subtypes of melanocytic nevi that are
distinguished based on their clinical and
histologic features;
Pathogenesis
acquired mutations that lead to constitutive
activation of NRAS or the serine/ threonine kinase
BRAF, which lies immediately down- stream of RAS
nevi only rarely give rise to melanomas
oncogene-induced senescence ;
Expression of either activated RAS or BRAF in
normal
human melanocytes causes only a
limited period of
proliferation
followed by a permanent growth arrest
mediated by the accumulation of p16/INK4a
Morphology
Common acquired melanocytic nevi are
tan to brown, uniformly pigmented,
small (usually less than 6 mm across),
relatively flat macules or elevated
papules with well defined, rounded
borders
May become more prominent during
pregnancy
Deeper nevus
Superficial cell are:
larger
tend to produce melanin
and grow in nest
are:
smaller
produce little or no
pigment
appears as cord and
Morphological changes
over
consist
of aggregates
or
most junctional
nevi grow
nests
of underlying
round cells that
into
the
time
grow along
the or cords
dermis
as nests
Junctional nevi
Compound
nevi
Intradermal
nevi
dermoepidermal
junction
of cells
Grossly,
lesions
arecombine
small,
compound
nevi
relatively
at, of
symmetric,
the features
and uniform.
junctional
nevi
(intraepidermal nevus cell
nests) with nests and cords
of dermal nevus cells.
In older lesions the
epidermal nests may
be lost entirely
Dysplastic Nevi
May be direct precursors of melanoma
Probability of dysplastic nevus to develop
melanoma
over 50% by age 60
the vast majority of such lesions are clinically
stable and never progress
Pathogenesis
acquired activating mutations in the NRAS and
BRAF genes
inherited loss of function mutations in CDKN2A.
negative regulator of cyclin-dependent kinase 4
(CDK4)
CDKN2A encodes PI6/INK4A
it appears that RAS or BRAF activation and
increased CDK4 activity contributes to the
development of dysplastic nevi.
Morphology
larger than most acquired nevi (often
greater than 5 mm across)
flat macules, slightly raised plaques
with a pebbly surface, or target-like
lesions with a darker raised center and
irregular at periphery
dysplastic nevi occur on both sunexposed and protected body surfaces.
dysplastic nevi usually involve both the
epidermis and the dermis
Nevus cell nests within the epidermis may
be enlarged and coalescence with adjacent
nest
lentiginous hyperplasia.
Melanin incontinence diagnosis is based
on this features
Linear fibrosis
Melanoma
most deadly of all skin cancers and is
strongly linked to acquired mutations caused
by exposure to UV radiation in sunlight
relatively common neoplasm
other sites of origin include the mucosal surfaces
reported incidence of melanoma; more than
76,000 cases and more than 9,700 deaths are
expected in the United States in 2014.
pathogenesis
About 10% to 15% of melanomas are inherited
as an autosomal dominant trait with variable
penetrance
majority of melanoma is sporadic : ultraviolet
radiation (UVR) damage from sun exposure
most commonly arise on sun-exposed surfaces;
the upper back in men and the back and legs in
women
mutation that disrupts cell cycle control genes
CDKN2a
P15/INK4
b
P16/INk4
a
Inhibits
CDK4 and
CDK6
P14/ARF
Enhance the
activity of p53
tumor supressor
Mutations that activate pro-growth
signaling pathway
increases in RAS and PI3K/ AKT signaling
activating mutations in BRAF -seen in
40% to 50% of melanomas
loss of the PTEN tumor suppressor, leading to
heightened activation of the PI3K/ AKT pathway
activating mutations in NRAS- additional
15%-20% of tumor
Mutations that activate telomerase.
reactivation of telomerase have a key
role in the development of most
melanomas
Morphology
melanomas show
striking variations in
color, appearing in shades of black,
brown, red, dark blue, and gray
The borders of melanomas are
irregular and often notched. Unlike the
smooth, round and uniform boarders of
MN
Progression of melanoma- has 2 phases
1.Radial growth
.horizontal spread of melanoma within the
epidermis and superficial dermis
.tumor cells seem to lack the capacity to
metastasize
.lentigo maligna- indolent lesion that
remain in the radial phase for several
decades. Usually involving sun-exposed
skin
.Acral/ mucosal lentiginos- melanoma that is
unrelated to sun exposure.
2. Vertical growth phase
during which the tumor cells invade
downward into the deeper dermal layers as
an expansile mass
heralded by the appearance of a nodule
and correlates with the emergence of a
tumor subclone with metastatic
potential
The probability of metastasis in such lesions
correlates with the depth of invasion,Breslow Thickness
Prognostic factor
Variables thats used in the probability of metastatic
spread:
Tumor depth (Breslow thickness)
Number of mitoses
Evidence of tumor regression
Ulceration of overlying skin
Presence and number of tumor infiltrating lymphocytes
Gender
Location
Clinical feature
ABCDEs of melanoma ( warning signs)
1.
2.
3.
4.
5.
Asymemetry
Irregular Boarders
Variated Color
Increasing Diameter
Evolution or change overtime
Melanoma of the skin is
usually asymptomatic,
although itching or pain may
be early manifestations.
majority of lesions are >10
mm in diameter at diagnosis.
most consistent clinical signs
are changes in the color, size,
or shape of a pigmented
lesion.
Benign epithelial tumors
common tumors that are derived from the
keratinizing stratified squamous epithelium
of
epidermis
hair follicle
ductular epithelium of cutaneous
glands.
Seborrheic Keratoses
occur most frequently in middle-aged or older
individuals.
Arise particularly numerous on the trunk,
although the extremities, head, and neck may
also be involved.
dermatosis papulosa nigra.- multiple small
lesions on the face
pathogenesis
Activating mutations in the fibroblast growth factor
receptor-3
Seborrheic keratoses may suddenly appear in large
numbers as part of a paraneoplastic syndrome- (LeserTrlat sign)
morphology
characteristically appear as round, at,
coinlike, waxy plaques that vary in diameter
from millimeters to several centimeters
uniformly tan to dark brown
velvety to granular surface.
Inspection usually reveals small, round, porelike ostia impacted with keratin
Histologic findings
exophytic and sharply demarcated from the
adjacent epidermis.
Hyperkeratosis occur at the surface
Characteristic feature- small keratin-filled
cysts (horn cysts) and invaginations of keratin
into the main mass (invagination cysts)
Acanthosis Nigricans
important cutaneous sign of several
underlying benign and malignant
conditions
marked by thickened, hyperpigmented skin
with a velvet-like texture
commonly appears in the flexural area
2 types based on the underlying cause
1. Acanthosis nigricans is associated
with benign conditions and develop
gradually
2. arises in association with cancermost commony gastrointestinal
adenocarcinoma
Pathogenesis
unifying feature of acanthosis nigricans is a
disturbance that leads to increased growth
factor receptor signaling in the skin
Familial form- germline activation mutation in
tyrosine kinase FGFR3
DM2 , hyperinsulinimia is believe to provoke
increased stimulation of IGFR1
maybe seen together with skeletal deformitiesachondroplasia and thanatropic dysplasia
Morphology
All forms of acanthosis nigricans have similar
histologic feature;
The epidermis and underlying enlarged dermal papillae
undulate sharply to form numerous repeating peaks and
valleys.
hyperplasia may
be seen, along
with
hyperkeratosis
and slight basal
cell layer
Fibroepithelial Polyp
crochordon, squamous papilloma, skin tag
is one of the most common cutaneous
lesions
middle-aged and older individuals on the
neck, trunk, face, and intertriginous areas
vast majority of polyps are sporadic.
can occasionally be associated with
diabetes, obesity, and intestinal polyposis
morphology
Fibroepithelial polyps are soft, fleshcolored, bag-like tumors
attached to the surrounding skin by a
slender stalk
consist of fibrovascular cores covered
by benign squamous epithelium
Epithelial or Follicular Inclusion Cyst (Wen)
common lesions formed by the invagination and
cystic expansion of the epidermis or hair follicle
Lay term is wen
they may be subject to traumatic rupture.
can spill keratin into the dermis
lead to an extensive and often painful
granulomatous inflammatory response
