Skin Pathology

DR. Willy Sandhika, dr., M.Si, Sp.PA(K)

Patologi Kulit - Makroskopis

 Makula : bercak datar berbatas jelas
 Erythema: bercak warna kemerahan
 Papula : penonjolan padat uk. < 5 mm
 Nodul : penonjolan padat uk. > 5 mm
 Plaque : lesi menonjol permukaan datar >
5 mm
 Vesicle : lesi menonjol berisi cairan < 5 mm
 Bulla : lesi menonol berisi cairan > 5 mm
 Pustule : vesikelberisi pus
 Wheal : daerah pruritik menonjol,
kemerahan.

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 Patologi Kulit - Mikroskopis
 Hiperkeratosis: penebalan / hiperplasia stratum
corneum
 Parakeratosis: retensi inti pd stratum corneum
 Acanthosis: hiperplasia epidermal
 Diskeratosis: keratinisasi abnormal di bawah stratum
granulosum
 Acantholysis: hilangnya hubungan interseluler antar
keratinosit.
 Papillomatosis: elongasi / pelebaran papilla dermis
 Erosi: hilangnya kontinuitas epidermis setempat /
sebagian
 Ulserasi: hilangnya kontinuitas epidermis total, s/d
dermis.

Skin Pathology
1. Inflammatory Dermatoses
1. Infectious Disease
2. Non – Infectious Disease
2. Pigmented Lesion
3. Neoplastic Disease
1. Epithelial Tumor (epidermis and skin
adnexa)
2. Mesenchymal Tumor (dermis)
3. Tumor of inflammatory cells

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1. Non – Neoplastic Disease (Inflammatory
Dermatoses)
 Disorders of Epidermal Maturation

 Acute Inflammatory Dermatoses

 Chronic Inflammatory Dermatoses

 Blistering (Bullous) Disease

 Disorders of Epidermal Appendages

 Infection

Disorders of Epidermal Maturation

ICHTYOSIS
 genetically inherited disorders is associated
with chronic, excessive keratin buildup
(hyperkeratosis) that results clinically in fish-
like scales
 ichthyosis vulgaris (autosomal dominant or
acquired), congenital ichthyosiform
erythroderma (autosomal recessive), lamellar
ichthyosis (autosomal recessive), and X-
linked ichthyosis

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Morfology
 buildup of compacted stratum corneum that is
associated with loss of the normal basket-
weave pattern
 little or no inflammation

 Variations in the thickness of the epidermis

and the stratum granulosum and the gross
appearance and distribution of lesions are
used to subclassify
Pathogenesis
 defective desquamation  retention of
abnormally formed scale

Acute Inflammatory Dermatoses

1. Urticaria
2. Acute Eczematous Dermatitis
3. Erythema Multiforme

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Urticaria
 localized mast cell degranulation and dermal
microvascular hyperpermeability.
 pruritic erythematous, edematous, circular
plaques = wheals.
 Microsc: superficial dermal edema and dilated
lymphatic and blood-filled vascular spaces;
the epithelium is normal.
 Collagen bundles are more widely spaced
than in normal skin  eosinophils

ACUTE ECZEMATOUS DERMATITIS

Classification based on initiating factor:
(1) allergic contact dermatitis
(2) atopic dermatitis
(3) drug-related eczematous dermatitis
(4) Photo-eczematous dermatitis
(5) primary irritant dermatitis.

Characterized with spongiosis  spongiotic

dermatitis
Edema in epidermis ± intraepidermal blister

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Microsc :
 Characterized by Spongiosis = spongiotic
dermatitis.
 progressive accumulation of intercellular
fluid  intraepidermal vesicles
 superficial, perivascular, lymphocytic
infiltrate +/- eosinophils associated with
papillary dermal edema and mast cell
degranulation.

ERYTHEMA MULTIFORME
 superficial perivascular, lymphocytic infiltrate
with dermal edema and accumulation of
lymphocytes along the dermoepidermal
junction + degenerating and necrotic
keratinocytes  interface dermatitis.
 Discrete and confluent zones of epidermal
necrosis occur with concomitant blister
formation.
 The clinical targetoid (target-like) lesion
shows central necrosis surrounded by a rim
of perivenular inflammation

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Chronic Inflammatory Dermatoses

1. Psoriasis (vulgaris)
2. Seborrheic Dermatitis
3. Lichen Planus

PSORIASIS
 well-demarcated, pink to salmon-colored
plaque covered by loosely adherent scale
that is characteristically silver-white in
color
 one cause of total body erythema and
scaling known as erythroderma

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Microsc:
 Acanthosis + regular elongation of the rete
ridges
 The stratum granulosum is thinned or
absent, and extensive overlying
parakeratotic scale is seen
 Neutrophils form small aggregates within
slightly spongiotic foci of the superficial
epidermis (spongiform pustules) and
within the parakeratotic stratum corneum
(Munro microabscesses).

SEBORRHEIC DERMATITIS
 involves regions with a high density of
sebaceous glands, such as the scalp,
forehead (especially the glabella), external
auditory canal, retroauricular area,
nasolabial folds, and the presternal area
 Dandruff is the common clinical
expression of seborrheic dermatitis of the
scalp

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•both spongiotic dermatitis and psoriasis.
mounds of parakeratosis containing
neutrophils are present at the ostia of hair
follicles (so-called follicular lipping).

Lichen Planus

 Pruritic, purple, polygonal, planar papules,

and plaques of skin and mucosa
 a dense, continuous infiltrate of lymphocytes
along the dermoepidermal junction (interface
dermatitis)
 Degeneration, necrosis, squamatization of
basal layer
 Civatte body : anucleate necrotic basal cell

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 Lichen planus

polygonal papule has a white lacelike

pattern that is referred to as Wickham
stria

Blistering (Bullous) Disease

1. Inflammatory Blistering Disorders

 Pemphigus

 Bullous Pemphigoid

 Dermatitis Herpetiformis

2. Non-inflammatory Blistering Disorders

 Epidermolysis Bullosa and Porphyria

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Blistering (Bullous) Diseases

PEMPHIGUS
 autoantibodies anti- keratinocyte  intra-
epidermal blister with acantholysis.
 (1) pemphigus vulgaris, (2) pemphigus
vegetans, (3) pemphigus foliaceus, (4)
pemphigus erythematosus, and (5)
paraneoplastic pemphigus.
 Pemphigus vulgaris (>80%)  mucosa and
skin / oral ulcer; superficial vesicles &
bullae  rupture  shallow erosion

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Blistering (Bullous) Diseases
 Pemphigus foliaceous : more benign form
 Pemphigus vegetans : verrucous (wart-like)
plaques (not blister) - groin, axilla, flexural
surface
 Pemphigus erythematous – malar area of the
face (lupus erythematosus-like)
 Paraneoplastic pemphigus : assoc w/
malignancy esp. NHL

acantholysis, the dissolution, or lysis,

of the intercellular adhesions that
connect squamous epithelial cells

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Bullous Pemphigoid
IF : linear deposit of IgG & C --
basement membrane zone

 Older age
 Skin (local or general)  mucosa
 tense bullae, filled with clear fluid, on normal or
erythematous skin

Sub-epidermal, non-acantholytic blisters

Subepidermal blister with eosinophils +

lymphocytes  neutrophils, assoc w/ basal cell
layer destruction  subepidermal cleft.

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Dermatitis Herpetiformis

 Urticaria & grouped vesicles

 lgA to dietary gluten  gluten-free diet.
 Assoc w/ intestinal celiac disease
 Small microabscess at the tips of dermal
papillae subepidermal blister.
 IF : granular deposit IgA

Epidermolysis Bullosa
 mediated by non-inflammatory mechanisms
 inherited defects in structural proteins that
lend mechanical stability to the skin.
 junctional type: blisters occur in histologically
normal skin at the level of the lamina lucida
 dystrophic types: blisters beneath the lamina
densa, in association with defective
anchoring fibrils.

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Disorders of Epidermal Appendage
ACNE VULGARIS
Non - Inflammatory acne
 Open Comedones : small follicular papules
containing a central black keratin plug 
oxidation of melanin pigment
 Closed Comedones : small follicular papules
without a visible central plug

Inflammatory acne :
 erythematous papules, nodules, and pustules

 Acne conglobata : sinus tract formation and

physical scarring.

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Pathogenesis

1. Changes in keratinization of the lower

portion of the follicular infundibulum w/
keratin plug  block outflow of sebum
2. Hypertrophy of sebaceous glands or
increased activity due to hormonal
stimulation

3. Lipase-synthesizing bacteria
(Propionibacterium acnes) colonizing the
upper and midportion of the hair follicle,
converting lipids within sebum to pro-
inflammatory fatty acids;

4. Inflammation of the follicle associated with

release of cytotoxic and chemotactic factors

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Morfology
 Open or closed comedones, papules,
pustules, or deep inflammatory nodules
 Lymphohistiocytic infiltrates in and around
affected follicles. Extensive acute and chronic
inflammation accompanies follicular rupture.
 Dermal abscesses may form in association
with rupture and gradual resolution, often with
scarring, ensues.

Infection

1. Verrucae (Warts)
2. Molluscum Contagiosum
3. Impetigo

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VERRUCAE (WARTS)
 Children & adolescent,  HPV

(1) Verruca vulgaris

(2) Verruca plana or flat wart
(3) Verruca plantaris and verruca palmaris
(4) Condyloma acuminatum (venereal wart):
cauliflower-like masses  many cm in
diameter

verrucous or papillomatous epidermal

hyperplasia + cytoplasmic vacuolization
(koilocytosis)

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MOLLUSCUM CONTAGIOSUM
  poxvirus

 lesions -- skin and mucous membranes

 Microsc : cuplike verrucous epidermal

hyperplasia + molluscum body (large
cytoplasmic inclusion)

Impetigo

 Bacterial infection -- Staphylococcus aureus

 impetigo contagiosa and impetigo bullosa
 Microsc : accumulation of neutrophils
beneath the stratum corneum  subcorneal
pustule.

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 Bullous Impetigo

Bullous lesion develop in the superficial

layers of the epidermis. Large number of
neutrophils may be present.

2. PIGMENTED LESION
 Hyperpigmentasi
 Neoplastic

 Non – Neoplastic

 Hypopigmentasi
 Leukoderma : post-inflammatory
hypopigmentation
 Vitiligo : decrease of melanocytes

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 Disorders of Pigmentation &
Melanocytes

1. Freckles
2. Lentigo
3. Melanocytic Nevus
4. Dysplatic Nevus
5. Malignant Melanoma

Freckles (Ephelis) :
 most common pigmented lesions of
childhood
 tan-red or light brown macules - after sun
exposure
 increased amounts of melanin pigment
within basal keratinocytes
 The café au lait spots (in
neurofibromatosis)  freckles

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LENTIGO
 common benign localized hyperplasia of
melanocytes, often initiated in infancy and
childhood.
  freckles, lentigines do not darken when
exposed to sunlight
 linear (non-nested) melanocytic hyperplasia
restricted to the cell layer immediately
above the basement membrane that
produces a hyperpigmented basal cell layer

MELANOCYTIC NEVUS (PIGMENTED

NEVUS, MOLE)
 tan to brown, uniformly pigmented, small
(usually <6 mm across), solid regions of
relatively flat (macules) to elevated skin
(papules), well-defined, rounded borders.
 mutations in either BRAF or NRAS genes;
followed by growth arrest by p16/INK4a
(inhibitor of cyclin-dependent kinases
CDK4 and CDK6)

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 Type Nevus :
1.Junctional Nevus
2.Compound Nevus
3.Dermal Nevus
 Maturation of nevus cell

 Blue nevus : non-nested dermal infiltration,

often with associated fibrosis.
 Halo nevus : lymphocytic infiltration
surrounding nevus cells.
 Spindle and epithelioid cell nevus (Spitz
nevus) : fascicular growth of large, plump
cells with pink-blue cytoplasm; fusiform
cells
 Congenital nevus : deep dermal growth
around adnexa, neurovascular bundles,
and blood vessel walls

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DYSPLASTIC NEVUS
 precursors of melanoma (Clark, 1978)
 larger than acquired nevi (often >5 mm
across), flat macules, slightly raised
plaques with a “pebbly” surface.
Pathogenesis :
 Mutation of CDKN2A/p16 on chr 9p21 and
CDK4 (cyclin-dependent kinase 4) on chr
12q14.
 mutations in NRAS and BRAF genes (
conventional nevi).

usually compound type and exhibit

both architectural and cytologic
atypia (nuclear enlargement,
irregular, often angulated nuclear
contours, and hyperchromasia).

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MELANOMA
 changes in the color, size, or shape of a
pigmented lesion, striking variations in color
 ABCD : (1) asymmetry; (2) irregular borders;
and (3) variegated color (4) diameter > 6 mm

Radial Growth Phase / Horizontal Spread:

tumor cells seem to lack the capacity to
metastasize
 lentigo maligna
 superficial spreading melanoma

 acral/mucosal lentiginous
melanoma

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Vertical Growth Phase :
 tumor cells invade downward into the
deeper dermal layers as an expansile
mass
 Nodular melanoma

 emergence of a clone of cells with

metastatic potential

Melanoma Prognostic Factors

(1) tumor depth Breslow thickness <1.7
mm (or Clark’s level 5th)
(2) number of mitoses
(3) evidence of tumor regression
(presumably due to the host immune
response)
(4) the presence and number of tumor
infiltrating lymphocytes (TILs)
(5) gender  female
(6) location (central body or extremity).

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 Skin Tumors (Neoplastic Lesion)

Epidermal Tumor
1. Benign : Seborrheic Keratosis
2. Pre-malignant : Actinic Keratosis
3. Malignant :
 Squamous Cell Cracinoma

 Basal Cell Carcinoma

SEBORRHEIC KERATOSES
 round, flat, coin-like, waxy plaques that vary
in diameter (mm – cm) ; tan to dark brown
and have a velvety to granular surface
 Microsc : exophytic and sharply demarcated
from the adjacent epidermis, composed of
sheets of small cells that most resemble
basal cells + variable melanin pigmentation.
 Hyperkeratosis at the surface + small
keratin-filled cysts (horn cysts) and
invaginations of keratin into the main mass
(invagination cysts) are characteristic
features.

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ACTINIC KERATOSIS
 < 1 cm in diameter; tan-brown, red, or
skin-colored; rough, sandpaper-like
consistency, + “cutaneous horn”
 Cytologic atypia is seen in the lowermost
layers of the epidermis and may be
associated with hyperplasia of basal cells
+ Parakeratosis

SQUAMOUS CELL CARCINOMA

 nodular, variable keratin production
(hyperkeratotic scale), may ulcerate
 Ca insitu : sharply defined, red, scaling
plaques
 Microsc : anaplastic squamous epithelial
cells w/ variable differentiation, invasion
into dermis

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BASAL CELL CARCINOMA
 pearly papules often containing prominent,
dilated subepidermal blood vessels
(telangiectasias)
 rodent ulcers : ulceration in advanced
lesions + extensive local invasion of bone
or sinuses
 superficial basal cell carcinoma:
erythematous  pigmented plaque 
resemble early forms of melanoma.

Microsc :
 cords and islands of basophilic cells with
hyperchromatic nuclei, embedded in a
mucinous matrix, and often surrounded by
many fibroblasts and lymphocytes.
 The cells at the periphery of the tumor cell
islands arranged radially with their long
axes in parallel alignment (palisading).
 The stroma retracts away from the
carcinoma, creating clefts or separation
artifacts.

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Tumors of the Dermis

1. Dermatofibroma
2. Dermatofibrosarcoma Protuberans

Dermatofibroma

 = Benign Fibrous Histiocytoma

 benign, spindle-shaped cells arranged in a
well-defined, nonencapsulated mass within
the mid-dermis
 overlying with epidermal hyperplasia /
pseudo-epitheliomatous hyperplasia

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Dermatofibrosarcoma Protuberans

 well-differentiated, primary fibrosarcoma of

the skin
 slow growing, locally aggressive, recurrence,
rarely metastasize.
 cellular, composed of fibroblasts arranged
radially (storiform pattern).

Tumors of the Inflammatory Cells

1. Cutaneous T-Cell Lymphoma :

Mycosis Fungoides & Sezary Syndrome

2. Mastocytosis : increased numbers of mast

cells in the skin

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MYCOSIS FUNGOIDES (CUTANEOUS T-
CELL LYMPHOMA)
 Patch stage : ill-defined patches w/ a fine
scale
 Plaque stage : well-demarcated lesions
which are annular or arciform in
arrangement
 Tumor stage : nodul +/- ulceration

 seeding of the blood by malignant T cells is

accompanied by diffuse erythema and
scaling of the entire body surface
(erythroderma) = Sézary syndrome

Microsc :
 Sézary-Lutzner cells (T-helper cells
(CD4+) form band-like aggregates within
the superficial dermis and invade the
epidermis as single cells and small
clusters (Pautrier microabscesses).
 hyperconvoluted or cerebriform contour.

 epidermotropism

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Mycosis Fungoides / Sezary Syndrome
 Tumor of CD 4+; w/ cerebriform nuclei
 Different manifestation, skin predilection
 MF : inflammatory premycotic phase 
plaque phase  tumor phase ; infiltration of
epidermis & upper dermis by tumor cells,
extracutaneous spread (lnn, bone marrow)
 SS : generalyzed exfoliative erythrodermia ;
rarely form tumor,  leukemia of Sezary cells

Mastocytosis
 Urticaria pigmentosa : multiple & widely
distributed, round to oval, red-brown,
nonscaling papules and small plaques
 Solitary mastocytomas : one or several pink
to tan-brown nodules that may be pruritic or
show blister formation
 Systemic mastocytosis : lesions similar to
urticaria pigmentosa, accompanied by mast
cell infiltration of bone marrow, liver, spleen,
and lymph nodes

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Morphology :
1. Subtle increase in the numbers mast cells --
large numbers mast cells in the upper to
mid-dermis.
2. Mast cells can be visualized with special
metachromatic stains (toluidine blue or
Giemsa)
3. Failure to recognize these cells by LM 
IHC mast cell tryptase.

ROBBINS AND COTRAN PATHOLOGIC

BASIS OF DISEASE, 8/ED © 2010

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