PATHOLOGY OF SKIN

ACUTE INFLAMMATION
Urticaria
Acute eczema
Erythema multiforme
 urticaria
Pathogenesis
-Follows exposure to pollens, foods, drugs, pressure, temperature
etc.
-Ag + IgE ->localized Mast cell degranulation->dermal
microvascular permeability->perivascular inflammatory infiltrate
by mononuclear cell (lymphocytes,s/t eosinophils, rare neutrophil)
-resulting erythematous,edematous,pruritic plaque

*Hereditary angioneurotic edema=Congenital C1 esterase inhibitor

deficiency causes uncontrolled complement activation and
urticaria
 ACUTE ECZEMATOUS DERMATITIS
A number of condition which varied
underlying aetiology.
New lesion: papule often with vesicles which
ooze and become crusted
With persistence: lesion developed into raised
scaling plaque
The nature and degree of these changes vary
among the clinical subtype
 ECZEMA
Pathogenesis:
Hypersensitivity Reaction:
- Initial exposure to antigen:
Antigen processed by Langerhans cells and presented to T
cells in the lymph node-> T cell activation ->memory cells.
Re-exposure to antigen:
-Quick (memory T cells) response ->inflammation
->urticaria, erythema, wet eczema
Persistence of antigen stimulation: Chronic inflammation
->Acanthosis, hyperkeratosis (lichenification) dry eczema.
 Histology
Spongiotic dermatitis (oedema fluid seeps into
epidermis,where it splay apart keratinocytes)
Intracellular bridges are stretched and become more
prominent and are easier to visualized
Superficialperivascular lymphocytic infiltrate,edema of
dermal papillae and mast cell degranulation.
Eosinophil prominent in spongiotic eruption provoked
by drug
In ganeral the histologic features are similiaar
regardless of cause
 Macroscopic
-Targetoid appearance: target skin lesion
consist of pale central blister or zone of
epidermal necrosis surrounded by macular
erythema
Microscopic
-superficial perivascular,lymphocytic infiltration,
associated with dermal oedema and margination
of lymphocyte along the dermoepithelial jx in
intimate ass w degenerating keratinocyte (dark
shrunken nuclei and eosonophilic cytoplasm that
undergoing apoptosis)
 Chronic inflammation
Chronic eczema
Psoriasis
Lichen planus
 Psoariasis-pathogenesis
Multifactorial:
genetic and immune strong association HLA-C and
environmental factor contribute the risk
Sensitized T cells infiltrate the skin and secrete cytokines
and growth factors and induce keratinocyte
hyperproliferation
Vascular proliferation angiogenesis
Trauma precipitates lesions Koebner phen.
Multi system disorder:
Arthritis, myopathy, enteropathy, Immunodef.
 Macroscopic:

Well demarcated pink to salmon colored plaque

covered by loosely adherent silver white scale
Auspitz sign:Removal of the scales result in small
pintpoint bleeding because of increase vascularity
under focal area of epidermal thinning. This
feature occur only in psoriasis
Koebner phanomenon: development of
isomoprphic psoriatic lesion immediately
subsequent to and at the site of a cutaneous injury
 Microscopic appearance

Marked epidermal thickening (achantosis)

Regular downward elongation of the rate ridges (test tube in
rack)
Increase epidermal cell turn over and lack of maturation
result in loss of the stratum granulosum and extensive
parakeratosis scale
Thinning of the epidermal layer overlying the tip of dermal
papillae.this velles bleed readily when the scales is removed-
multiple punctate bleeding point
Neutrophils form small aggregate within both the spongiotic
superficial epidermis and the parakeratotic startum corneum
 Lichen planus
Pruritic,purple,polygonal,planar papule and
plaques describe tnid disorder of skin and
squamous mucosa
Pathogenesis:lesion result from CD8 T cell
against Ag in the basal layer and
dermoepidermal jx that are produce by unkown
mech.Perhaps as a consequence of a viral
infection or drug exposure
Self limited 1-2 yrs
Macroscopic
Flat topped pink-purple polygonal papule has white
lace like marking referred to as Wickham striae
Microscopic
Band-like infiltrate of lymphocyte along the
mucoepidermal jx,herperkeratosis,
hypergranulosis and pointed rate ridge
(sawtoothing) which resullts from chronic injury of
the basal cell layer
 LICHEN SIMPLEX CHRONICUS
Manifest as a roughening of the skin
It is a response to a local repetative trauma
such as cont rubbing or scratching
Pathogenesis: the trauma probably induce
epithelial hyperplasia and eventually
epidermal scarring
Microscopic:
Achantosis,hyperkeratosis and hypergranulosis
Elongation of the rete ridges, fibrosisof the
papillary dermis and a chronic inflammatory
infiltrate
These lesion are similar in appearance to normal
skin of palm and sole in which the thickening
serves as an adaptation to repetative mechanical
stress
 infection
Bacteria (acne,impetigo)
Viral (wart,moluscum contagium,
 microscopic
Acne is a special form of folliculitis.
Follicular plugging with entrapped bacteria
and hairs
Intrafollicular pustules
Ruptured pilosebaceous apparatus
Mixed perifollicular inflammatory infiltrate
Sometimes abscesses, sinus tracts and
scarring
 impetigo
Characterized by accumulation of neutrophil
beneath the startum corneum that often
produce a subcorneal pustule.
Organism staph aureus, strep pyogenes
Person colonized by s.aureus or s pyogenes
are more likely to be affected
Bullous impetigo
 Verrucae (wart)
Most wart caused by low risk HPV subtype that
lack malignancy transforming potential
Like high risk viruses,these low risk viruses
express viral E6 and E7 oncoprotien that lead to
dysregulated epidermal cell growth & increase
survival
Infection thru direct contact or autoinoculation
Self limited,regress spontaneously 6m-2yrs
 Type of wart
Based on their gross appearance,location and
cause by distinct HPV subtype
Verruca vulgaris:most common type,found on
dorsal aspect of hand,periungual
Verruca plana/flat wart: flat smooth and tan
macules
Verruca plantaris/plantaris:on sole/palm
Condyloma accuminatum (vanereal wart): on
genitelia
 histology
Epidermal hyperplasia often undulant in character
(so called verrucous or papillomatous epidermal
hyperplasia)
Cytoplasmic vacuolisation (koilocytosis) which
involve the more superficial epidermal layer
producing halos of palor surrounding infected nuclei
Infected cell also demonstrate prominent
keratohyalin ganules and jagged eosonophillic
intracytoplasmic protein aggregates as a result of
impared maturation
warts
 Viral wart
Koliocytes
Evidence of viral infection.
Rasinoid nucleus
surrounded by a halo. Can
be found in all warts, but
most easily found in
condyloma accumulata.
 Moluscum contagiosum
Caused by a poxvirus.
Umbilicated papules.
Found in children and immunocompromised.
Spread by direct contact with lesions and by fomites.
histology:
Epidermal hyperplasia
Little to dense mixed inflammatory cell infiltratioN
Will have intracytoplasmic inclusions (molluscum
bodies) within keritinocytes.
Moluscum contagiosum
 BLISTERING DISORDER
Pemphigus
Pemphigoid
Dematitis herpetiformis
 pemphigus
Rare autoimmune blistering d/o resulting from loss of
normal intracellular attachment within the epidermis and
the squamous mucosal epithelium
In elderly, women
3 major variant
1.pemphigus vulgaris*
2.pemphigus foliaceus*
3.paraneoplastic pemphigus (ass w internal malignancy)
*autoimmune dss, type II hypersensitivity reaction,IgG
autoAb bind to intracellulat desmosomal protein type 1 and
3 of skin mucosa membrane->disrupt the intracellular
adhesive fx
 Pemphigus-morphology
Pemphigus vulgaris:
-most common type,involve both mucosa
and skin. Lesion are superficial flaccid vesicles
and bullae ruptured easily leaving deep and
extensive erosion covered with a serum crust.
Pemphigus foliaceus:
rare,benign,bullae confine to skin,infrequent
mucous membrane involvement
 Common histology findings
Acantholysis:lysis of the intracellular adhesive jx bw
neighboring squamous epithelial cell that result in
rounding up of detached cell
In phemphigus vulgaris acantholysis selectively
involve the layer of the cells immediately above the
basal layer giving rise to suprabasal acantholytic
blister
In pemphigus foliaceus acantholysis involvethe
superficial epidermis at the level of stratum
granulosum
 Bullous pemphigoid
Acquired blistering d/o w an autoimmune dss
Triggered by Ig autoAb to hemidesmosom
(basement membrane attachment plaque)
component fix complement and coz tissue
injury by recuiting neutrophil and eusinophil.
Bullae not ruptured easily
Tend to remit and relapse
Response to immunosuppressive drug
Gestational pemphigoid (herpes gestational)
A clinical distinct subtype that appear during
2nd-3rd trimester
Also cause by autoAb against BPAG
Typically resolved after childbirth
 Macroscopic
Tense bullae filled w clear fluid on normal or erythematous
skin
Microscopic
-subepidermal nonacantholytic blister
-early lesion show perivascular lymphocyte
infiltration and superficial dermal edema ass w basal
cell layer vacuolization
-vacuolization give rise to a fluid filled blister
the blister roof consist of full-thickness epidermis w
intact intracellular jx (a key distinction from the
blister seen in pemphigus)
 Dermatitis herpetiformis
Autoimmune blistering d/o
Extremely pruritic urticaria & grouped vesicle
Male predominant, 30-40th decades
Occur in ass w coeliac dss (small portion)like
coeliac dss, dematitis herpertiformis responds
to a gluten-free diet
 Dermatitis herpetiformis
Pt developed IgA Ab to dietary gluten
IgA Ab also cross react w endomysium and
tissue transglutaminases including epidermal
transglutaminase expresses by keratinocyte
Injury and inflammation produce a
subepithelial blister
BENIGN SKIN LESION
 SEBORRHIC KERATOSIS
Common pigmented epidermal tumour
Middle aged-older pt
Arise spontaneously
Hudred of lesion may appear suddenly as a
paraneoplastic syndrome (sign of Lesser-
Trelat).Pt w this presentation may habour
internal malignancy, most commonly GIT ca
which produce growth factor that stimulate
epidermal proliferation
 Macroscopic
round,exophytic coin like plaque varying in
diameter from mm to cm that have stuck-on
appearance.they are tan to dark brown, have a
velvety to granular appearing surface.Their drak
brownocc suggestive of melanoma
Microscopic
Composed of monotonous sheet of small cell that
resemble the basal cell of the normal epidermis.variable
melanin pigmentation is present within this basaloid cell.
Hyperkeratosis occur at the surface and the presence of
keratin-filled cyst (horn cyst) and down growth of keratin
into the main tumor mass (pseudo horn cyst) are
characteristic feature
MALIGNANT SKIN DISORDER
 SCC
<5% have mets to regional nodes at dx bcoz
often discovered while small n resectable
Tumor arise from actinic keratoses may be
locally aggressive
Mucosal squamous cell ca generally are more
aggressive
 Macroscopic:
sharply defiine,red scalling plaques many arise from
prior actinic keratoses,more advance invasive lesion
are nodular show variable scale and may ulcerate
Microscopic
Highly atypical cell at all level of epidermis w
nuclear crowding and disorganisation.
Invasive tumor define by penetration of the
basement membrane, show variable degree of
differentiation,ranging from tumot arrange in orderly
lobule that exhibit extensive keratinization to
neoplasm consisting of anaplastic cell w foci of
necrosis and abortive
 Microscopic
-the tumor cell resemble the normal
epidermal basal cell layer from which they
qare derived.bcoz they may arise from either
the epidermis or the follicular epithelium
2 common pattern are seen
1. multifocal growth originating from the epidermis
(superficial pattern)
2.nodular lesion growing downward into the
dermis as cord and island
The cell are basophilic,hyperchromatic nuclei
embedded in a fibrotic or mucinous stroma
matrix.peripheral tumor nuclei align in the outermost
layer in pallisading pattern which often separates
from the stroma creating a characteristic cleft
 Malanocytic proliferation
Melanocytic nevi
Refer to any benign congenital or acquired
neoplasm of melanocyte
Macroscopic: tan to brown uniformly pigmented
rounded border
Early lesion are composed of round to oval cell
that grow in nest along the dermoepithelial jx
Nuclei are uniform and round, contain
inconspicuous nucleoli w little or no mitotic actvt
Melanocytic nevi
Junctional nevi: early lesion that grow along the
dermoepithelial jx
Compound nevei: eventually most jx nevi growth
into the underlying dermis as nest or cord of cell
Intradermal nevi: in older lesion,the epidermal
nest may be lost entirely
*compound and intradermal nevi often are more
elevated than jx nevi
Dysplastic nevus
May be sporadic or familial
The familial potential precursor of melanoma
Life time risk is closed to 100%
In sporadic cases only if dysplastic nevi>10 are at
risk of melanoma
Tend to occur on body surface not expose to sun
Most melanoma arise de novo and not from pre
existing nevus
 MELANOMA
Most lesion arise in skin
May also involve the oral and anogenital mucosa
surface,oesophagus,meninges and eye
Skin melanoma usu asymp
The most important clinical sign
-rapid enlarge of pre existing nevus
-Itching or pain in a lesion
-Development of a new pigmented lesion during adult life
-irregularity of the borders of a pigmented lesion
-vegetation of a color within a pigmented lesion
 The probability of mets is predicted by
measuring the depth of invasion (breslow
thickness) measure in mm
Mets risk also is increase in tumour with a
high mitotic rate and in those who failed to
induce a local immune response
Mets not only to LN but other site that can be
seeded hematogenously