PATHOLOGY

THE SKIN
NORMAL STRUCTURE and FUNCTION
• LAYERS OF EPIDERMIS:
1. Stratus Basale: Contains Stem Cells. Some
minimal cell division occurs in this layer.
2. Stratum Spinosum: This is the main
proliferative layer. Some synthesis begins in
this level too.
• Membrane-Coating Granules (MCG)
begin formation in this layer, near the
top.
3. Stratum Granulosum: This is the mature
synthetic layer, where keratinocytes are
synthesizing the granular components
(Keratin, MCG) of skin.
4. (Stratum Lucidum): Only thick skin, a thin
layer of flat cells marking the uppermost
border of the Stratum Granulosum. They
aren't apparent in thin skin.
5. Stratum Corneum: 15-20 layers of
dehydrated, non-nucleated keratinocytes,
packed with tonofilaments containing
filaggrin.
• EPIDERMAL MIGRANT CELLS:
1. MELANOCYTES:
2. LANGERHANS CELLS:
3. MERKEL CELLS:
• DERMAL-EPIDERMAL BASEMENT MEMBRANE
ZONE:
1. LAMINA LUCIDA
2. LAMINA DENSA
• THE DERMIS
• HAIR FOLLICLES
DERMATOLOGY DICTIONARY
Types of Lesions:
1. Macule: A small, discolored patch or spot
on the skin, neither elevated above nor
depressed below the skin's surface.
2. Papule: A small, circumscribed, solid
elevation on the skin, less than 0.5 cm.
 3. Plaque: Slightly larger circumscribed
elevation, greater than 0.5 cm.
4. Vesicle: A small (less than 0.5 cm)
circumscribed elevation of the skin
containing fluid.
5. Bulla: A large blister appearing as a
circumscribed area of separation of the
epidermis from the subepidermal structure
(subepidermal bulla) or as a circumscribed
area of separation of epidermal cells
(intraepidermal bulla) caused by the
presence of serum, or occasionally by an
injected substance.
6. Pustule: A small circumscribed elevation of
the skin, containing purulent material.
7. Eczema: Generic term for inflammatory
conditions of the skin, particularly with
vesiculation in the acute stage, typically
erythematous, edematous, papular, and
crusting. Sometimes referred to colloquially
as tetter, dry tetter, scaly tetter.
• Followed often by lichenification and
scaling and occasionally by duskiness of
the erythema and, infrequently,
hyperpigmentation
• Often accompanied by sensations of
itching and burning
• The vesicles form by intraepidermal
spongiosis.
8. Nevus: It literally means a hamartoma. In
common use, a benign melanocytic
neoplasm of the skin, or mole.
Dermatological Structures:
9. Keratinocyte: A keratin-secreting stratified
squamous epithelial cell.
10. Panniculus: The superficial fascia which
contains an abundance of fat deposit in its
areolar substance.
11. Rete Ridges: Downward thickening of the
epidermis between the dermal papillae; peg
is a misnomer because the dermal papillae
 are cylindrical but the epidermal thickening
between papillae is not.
Dermatopathology:
12. Acanthosis: An increase in the thickness of
the stratum spinosum of the epidermis.
13. Acantholysis: Separation of individual
epidermal keratinocytes from their
neighbor, as in conditions such as
Pemphigus Vulgaris and Darier's disease.
14. Parakeratosis: Retention of nuclei in the
cells of the stratum corneum of the
epidermis, observed in many scaling
dermatoses such as psoriasis and subacute
or chronic dermatitis.
15. Hyperkeratosis: Thickening of the horny
layer of the epidermis or mucous
membrane.
SELECTED INFECTIONS with CUTANEOUS
MANIFESTATIONS
BACTERIAL INFECTIONS:
IMPETIGO: Staphylococcus Aureus. Weeping,
oozing lesions; red patches developing into
pustules.
SCALDED-SKIN SYNDROME: Staphylococcus
Aureus. Bullous lesions leading to
desquamation in infants.
• It is a result of the toxin -- not the bugs
themselves. No bugs are found in the
lesion.
• It will heal without scarring, if treated
carefully and not spread.
TINEA (RINGWORM): Fungal infection caused by
the dermatophytes, Epidermophyton,
Microsporum, and Trichophyton.
PATHOLOGY: The fungi infect the stratum
corneum layer of the epidermis. They don't
go any deeper.
SPECIFIC INFECTIONS:
• TINEA CRURIS: Jock itch does not occur
over mucous membranes, hence the
scrotum is not involved.
• TINEA CAPITIS: Head
 • TINEA CORPORIS: Trunk
• TINEA PEDIS: Feet
VIRAL INFECTIONS
HERPES SIMPLEX:
• Group Lesions: Characteristic lesion is
groups of vesicles, that may become
confluent, but that heal without
scarring.
VARICELLA-ZOSTER (CHICKEN-POX): Herpetic
lesions over dermatomal distribution.
HUMAN PAPILLOMAVIRUS (HPV): Causes
benign keratinocytic neoplasms.
• VERRUCA VULGARIS: Common warts,
HPV-2,4. Most frequent on dorsum of
hands or on face.
• PLANTAR WARTS: HPV-1, frequently
painful and difficult to get rid of.
• VERRUCA PLANA: HPV-3. Small flat
papules on the face.
• CONDYLOMA ACUMINATUM:
Venereal warts
• HPV-1,6 are the most common
causes.
• HPV-16,18 will lead to squamous
carcinoma of cervix.
• BOWENOID PAPULOSIS
• EPIDERMODYSPLASIA VERRUCIFORMIS
ERYTHEMA INFECTIOSUM (FIFTH DISEASE):
Caused by Human Parvovirus B19.
MOLLUSCUM CONTAGIOSUM: Caused by the
Molluscum Contagiosum poxvirus.
ARTHROPOD INFESTATIONS:
SCABIES: very itchy lesions, typically
between fingers.
• PATHOLOGY: Little red papules.
PEDICULOSIS:
ARTHROPOD BITES:
EPIDERMAL DISEASES of EXCESSIVE CORNIFICATION
ICHTHYOSIS:
DARIER DISEASE (KERATOSIS FOLLICULARIS)
PSORIASIS: Persistent, abnormal epidermal
squamous-cell hyperplasia.
PATHOGENESIS
GENETIC: Psoriasis has a genetic component.
The more severe the disease, the more likely
it is to be familial.
• HLA-B13, B17, Bw6 are found
commonly and indicate worse
prognosis.
ENVIRONMENT: Psoriasis is like a
hypersensitive response to normal injury
(physical, sunlight, chemical), except that it
doesn't go away after the injury.
• Inflammatory neutrophils probably
release Epidermal Growth Factor (EGF),
which stimulates excessive growth.
CELL-PROLIFERATION: Abnormal or
unregulated cell-proliferation occurs. There is
a decrease in the number of beta-receptors,
and decreased levels of cAMP, but the
mechanism is unclear.
MICROCIRCULATORY CHANGES: Capillary
loops in the dermal papillae become venular.
Neutrophils are thus attracted to the (venous)
vessels, and they accumulate in places where
they are not normally found.
• You see neutrophilic infiltrates in the
epidermal layers; normally they remain
in dermis.
PATHOLOGY
Hypergranulosis: Increased thickness of the
granular layer of the epidermis.
Parakeratosis: Cell-nuclei of keratinocytes
grow all the way up into the cornified layer,
where they are not supposed to be.
Elongation of Rete Ridges: Excessive
proliferation of the basal layer cause it to get
thrown into folds. Looks like a "picket fence."
Munro Microabscesses: Dense collections of
neutrophils in the stratum corneum.
SYMPTOMS: Large, erythematous, scaly plaques,
commonly on dorsal extensor surfaces.
Severity of disease varies.
 Psoriatic Arthritis (Rheumatoid negative) is
often also found.
TREATMENTS: Anthralin, topical
corticosteroids, systemic methotrexate in severe cases.
DYSHESIVE DISORDERS and RELATED DISEASES
PEMPHIGUS VULGARIS
PATHOGENESIS: Type-II (antibody-dependent
cellular cytotoxicity) hypersensitivity response
against squamous epithelial cells.
PATHOLOGY:
• Desmosomal Dissolution: Antibodies
to keratinocytes causes dissolution of
desmosomes ---> epidermis falls apart
(acantholysis)
• Acantholysis: Separation of the
stratum spinosum and outer epidermis
from the underlying basal epidermis.
• Acantholytic Cells: Rounded,
detached keratinocytes found in the
fluid of the bullae. In contrast to
erythema multiforme, these are vital
epithelial cells.
SYMPTOMS / CLINICAL:
• Bullae: Progressive flaccid bullae
resembling a second-degree burn,
which can be fatal.
• Nikolsky's Sign: Sliding thumb across
the skin separates the outer layer from
the underlying basal cells.
TREATMENT: Corticosteroids.
EPIDERMOLYSIS BULLOSA: Hereditary group of
disorders, in which blisters are formed in response
to minor trauma. Underlying defect involves easy
separation between the dermis and epidermis.
EPIDERMOLYTIC EPIDERMOLYSIS BULLOSA
(EB-SIMPLEX)
JUNCTIONAL EPIDERMOLYSIS BULLOSA
DERMOLYTIC EPIDERMOLYSIS BULLOSA
BULLOUS PEMPHIGOID: Autoimmune disease
similar to pemphigus, but acantholysis is absent.
PATHOGENESIS: Circulating IgG antibodies
bind to the BP antigen in the lamina lucida.
 The antigen is on basal cells that are attached
to hemidesmosomes, and binding causes
separation of the hemidesmosomes.
PATHOLOGY: Complement is activated as a
result of Ab-binding.
• Dermal-epidermal separation in the
lamina lucida occurs as a result. This
differs from acantholysis (separation
within the epidermis), as seen in
Pemphigus.
DERMATITIS HERPETIFORMS: Intensely pruritic
urticaria-like plaques over the extensor surfaces of
the body.
PATHOGENESIS: Related to gluten-
sensitivity in patients with HLA-B8 and HLA-
DRw3 haplotypes. The disease can be
controlled with gluten-free diet.
DISEASES of BASAL KERATINOCYTIC INJURY
ERYTHEMA MULTIFORME: Hypersensitivity
reaction to drugs or infectious agents.
PATHOGENESIS: Evidence of both Type-III and
Type-IV hypersensitivity reactions.
• Drugs: Sulfonamides, other drugs.
• Infectious agents: Herpes Simplex,
Mycoplasma.
PATHOLOGY:
• Sparse lymphocytic infiltrate into
epidermis.
• Necrosis and pyknosis of individual
epidermal cells.
SYMPTOMS: Characteristically, both skin and
mucous membranes are involved.
• Peak incidence 20's-30's.
• Target Lesions: Maculopapular rash
with characteristic target-lesions on
gross-inspection. The target-lesions
may coalesce to form large areas of
necrosis.
STEVENS-JOHNSON SYNDROME: Dreaded
complication, severe form of Erythema
Multiforme.
• TRIAD:
 Erythema Multiforme
Mucous membrane inflammation
(conjunctivitis, stomatitis,
urethritis, bronchitis)
Systemic involvement: fever,
headache, malaise
May also see (rare): glomerulonephritis, myocarditis,
arthritis, encephalitis.
LUPUS ERYTHEMATOSUS (SLE)
PATHOGENESIS: Involves both Type-III and
Type-IV autoimmune reactions.
Type-III: Deposition of anti-dsDNA immune complexes at
the dermal-epidermal junction.
Type-IV: T-Cell reactivity to basal cells.
PATHOLOGY / SYMPTOMS: Inflammatory
response ---> erythematous plaques --->
atrophy and scarring of epidermis.
Lesions start out hot, edematous, and swollen and end up
scarred, shrunken, and contracted.
Plaques are typically piecemeal, rather than confluent as
we see in Erythema Multiforme.
SUBTYPES
CHRONIC CUTANEOUS LUPUS ERYTHEMATOSUS
(DISCOID LUPUS): A non-systemic disease only of the
skin.
PATHOLOGY: Discoid papules with hyperkeratotic
margins and a depigmented center.
SYMPTOMS: Lesions usually limited to face, scalp, and
ears.
SUBACUTE CUTANEOUS LUPUS ERYTHEMATOSUS:
May see musculoskeletal involvement, but further
systemic involvement is rare.
SYMPTOMS: Lesions occur in classic photosensitive areas:
(1) malar rash, and (2) V-neck area of upper chest.
ACUTE CUTANEOUS LUPUS ERYTHEMATOSUS: Full
blown disease with systemic involvement.
LICHEN PLANUS: Chronic eruption of flat-topped,
shiny, violaceous papules on flexor surfaces, male
genitalia, and buccal mucosa of unknown cause.
PATHOLOGY: It may form linear groups of
lesions.
Microscopically characterized by a bead-like
subepidermal lymphocytic infiltrate.
CLINICAL: Spontaneous resolution is common
after months to years.
INFLAMMATORY DISEASES of VASCULAR BEDS:
The most common diseases of the skin occur by
allergic reactions.
URTICARIA and ANGIOEDEMA:
URTICARIA (HIVES)
PATHOGENESIS: Type-I immediate-type, IgE-mediated
hypersensitivity against a variety of antigens.
IgE sticks to Mast Cells and basophils.
Subsequent interaction with antigen causes
degranulation ---> local and systemic inflammatory
responses.
PATHOLOGY: Raised, pale, pruritic papules and plaques
that appear and disappear within a few hours.
The epidermis remains untouched in a pure urticarial
reaction. The reaction is a vasodilation and inflammatory
infiltrate (lymphocytes, eosinophils) of the underlying
dermis.
ANGIOEDEMA :Edema involves the deeper
dermis and subcutaneous tissues.
DERMATOGRAPHISM: Linear-hives with a rick-pink
flare, in which you can write on the lesion and the
impression sticks.
LEUKOCYTOCLASTIC VASCULITIS: Also known
as Cutaneous Necrotizing Venulitis,
Hypersensitivity Angiitis
PATHOGENESIS: Type-III immune-complex
reaction results in elaboration of complement
---> endothelial damage and fibrin deposition.
May be associated with HBV.
May occur in conjunction with SLE, RA, ulcerative colitis.
PATHOLOGY / CLINICAL: Small-vessel vasculitis
showing fibrinoid necrosis of small vessels.
Petechial hemorrhages.
ALLERGIC CONTACT DERMATITIS (POISON
IVY)
PATHOGENESIS: Type-IV delayed, cell-
mediated hypersensitivity reaction against
poison ivy in the epidermis. Antigens are
 taken up Langerhans cells and presented to T-
Cells.
PATHOLOGY:
Eczematous dermatitis, inflammatory reaction with
vesiculation.
Epidermal edema is seen, with T-Cell infiltrates.
DERMAL CONNECTIVE TISSUE DISEASES
SCLERODERMA (PROGRESSIVE SYSTEMIC
SCLEROSIS):
EOSINOPHILIA-MYALGIA SYNDROME:
PSEUDOXANTHOMA ELASTICUM:
SARCOIDOSIS:
INFLAMMATORY DISORDERS of PANNICULUS
ERYTHEMA NODOSUM: Septal Panniculitis
Without Vasculitis.
SYMPTOMS: Self-limited, tender nodules over
the extensor surfaces of the lower extremities.
PATHOLOGY: Inflammation of subcutaneous
tissues around the cutaneous septa.
PATHOGENESIS: Triggered by a variety of
drugs and bugs, and associated with various
diseases.
WEBER-CHRISTIAN DISEASE: Lobular Panniculitis
Without Vasculitis.
ERYTHEMA INDURATUM: Lobular Panniculitis
With Vasculitis.
ACNE VULGARIS:
MELANOCYTIC NEOPLASIA
BENIGN / PRE-MALIGNANT LESIONS:
MELANOCYTIC NEVUS (MOLE): Benign, melanocytic
neoplasm with symmetric, well-circumscribed margins,
with diameter less than 6 mm
Lentigo: A freckle. Melanocytes are limited to the basal-
cell layer.
Junctional Nevus: Melanocytes cluster at the tips of the
rete ridges.
Compound Nevus: Nests of melanocytes seen in the
epidermis and dermis.
Dermal Nevus: Intraepidermal melanocytic growth
ceases, and melanocytes are confined entirely to the
dermis.
Skin Tag: Dermal component is terminally differentiated
into neuro-mesenchyme, and all that is left is a skin tag.
ATYPICAL NEVUS: Nevus with abnormal
growth patterns. Cytologic atypia are not
found.
DYSPLASTIC NEVUS: Malignant nevus with
abnormal growth pattern and cytologic atypia.
TUMOR PROGRESSION
RADIAL GROWTH-PHASE MELANOMA:
Intermediate lesion. A dysplastic nevus, in the
dermal epidermal junction, that spreads
outward. At this point the lesion is curable by
wide excision.
VERTICAL GROWTH-PHASE MELANOMA:
By definition, a melanoma that has extended
into the lower half of the reticular dermis.
High-grade lesion with very high chance of
metastasis.
Cells may appear white or contain no pigment.
Dominant site of growth is shifted from the epidermis to
the dermis.
METASTATIC MELANOMA: Both lymphatic
and hematogenous. Every organ may be
involved, and widespread, multiple
metastases are common.
TYPES of MELANOMA
NODULAR MALIGNANT MELANOMA: Very
rare, deadly tumor that skips the radial growth
phases and arises as an already-anchored
malignant tumor in the vertical growth phase.
LENTIGO MALIGNANT MELANOMA: Also
called a senile freckle. Large, pigmented
macule that occurs on sun-damaged skin.
Invasion is not as prominent as in superficial
spreading melanomas.
ACRAL LENTIGINOUS MELANOMA: Most
common form of melanoma in dark-skinned
persons.
SYMPTOMS: Arises in palms, soles, or sub-uncal region.
Often presents as a pigmented streak on the nail-bed.
They are often picked up late and can metastasize. Hence
somewhat worse prognosis.
CLINICAL
NUMBER: The greatest single predictor of
whether a nevus will be malignant is the
number of nevi the patient has. Patients with
over 50 nevi on the body tend to develop a
melanoma.
CLARKE'S STAGING: Growth-Phase of Tumor
Stage I: Melanoma in situ, limited to epidermis.
Stage II: Radial-Growth-Phase melanoma that has
invaded the papillary dermis.
Stage III: Vertical-Growth-Phase melanoma that has
invaded the reticular dermis.
Stage IV: Vertical-Growth-Phase melanoma that has
invaded the collagen bundles beneath the reticular
dermis.
Stage V: Subcutaneous invasion, metastases.
ABCD CRITERIA: Things that indicate
malignancy.
Asymmetry of lesion
Borders are irregular
Color variation. Can see black, blue, red in the lesion.
White can be seen too and is an ominous sign, as it
generally means the lesion has already entered vertical
growth phase.
Diameter is larger than 6 mm.
PROGNOSTIC FEATURES:
Mitotic Rate: Aside from the growth-phase, it is the
most powerful indicator of prognosis. Patients with no
mitosis have a greater chance for survival.
Lymphocytic Response: An infiltrating, lymphocytic
response to the tumor is a good sign.
TREATMENT: Melanomas are resistant to
chemotherapy and radiation therapy. Once it
has metastasized, the prognosis is dismal.
OTHER BENIGN LESIONS:
CONGENITAL MELANOCYTIC NEVUS:
EPITHELIOID-CELL NEVUS (SPITZ TUMOR):
BENIGN KERATOSES: Precursor lesions to basal cell
and squamous cell carcinomas.
SEBORRHEIC KERATOSIS: The benign counterpart to
Basal Cell Carcinoma.
 CLINICAL: Benign, stuck on, sharply
demarcated papule or plaque. Lesion looks
like it was stuck on the skin and cut out with
a cookie cutter.
PATHOLOGY: Sheets of squamous cells that
resemble basal cells (basal keratinocytes).
Horn Cysts: Microscopic structures, indicating a benign
lesion.
The cells are thought to be derived from hair-follicle
germ-cells.
The cells resemble Basal Cell Carcinoma, except they do
not grow inward (invade), and never metastasize.
ACTINIC KERATOSIS: The benign counterpart to
Squamous Cell Carcinoma.
CLINICAL: Circumscribed, erythematous, scaly
patch or plaque, usually on the back of the
hand or the face.
Sand-paper lesions: They have characteristic sand-
paper quality when touched.
PATHOLOGY: Abnormal squamous cells begin
at the basal layer. As the lesion progresses,
atypia progress from the basal layer to the
surface. When the abnormal cells stretch from
the basal layer to the surface, then you have a
carcinoma in situ.
Parakeratosis: Keratinization in the lesion is not normal.
The keratin layer does not slough off normally and thus
accumulates, similar to psoriasis. Thus a plaque forms.
TREATMENT: Actinic Keratosis can be reversed
by withdrawing UV radiation and sometimes
applying cytotoxic treatment. But, it often
progresses to squamous cell carcinoma.
KERATOACANTHOMA
BASAL CELL CARCINOMA: Basal cell carcinoma is
the single most common malignant neoplasm in
human beings.
PATHOGENESIS: Caused by UV-light damage. Very
rare or unheard of in black skin, but very common
in white skin.
CLINICAL:
LOCATION: Basal cell tumors very commonly
occur in the head and neck region. Less often,
 they occur on upper body, but almost never
on lower body.
Pearly white papules are typical lesion, 2-3
mm in diameter. The lesions almost look
translucent on the naked skin.
The tumors can erode (superficial, central depression) or
ulcerate (deeper hole in center).
INVASIVE: In the gray-zone between benign
and malignant. They almost never
metastasize, but they can be very invasive
and destructive, so they're called malignant.
They can grow downward, right through the dermis, then
muscle, and then bone.
PATHOLOGY: Multiple nests and elongated fingers
of small, very basophilic epithelial cells.
Morphea-like Basal Cell Carcinoma: A
particularly nasty variant. Pale, tough, scar-
like tumor.
Tiny nests of basal cells in a very fibrotic stroma.
TREATMENT: Electrodesiccation and curettage.
SQUAMOUS CELL CARCINOMA
PATHOGENESIS: UV-light induced chromosomal damage.
Very rare in black skin.
Squamous Cell Carcinoma in situ: Essentially,
an actinic keratosis that spans the entire thickness
of the epidermis, but does not invade the dermis.
There is no clear cut line you can draw between
actinic keratosis and squamous cell carcinoma in
situ.
PATHOLOGY: Raised, hyperkeratotic lesions that
may ulcerate if large. The squamous cells regress
in maturity. In an advanced SCC, 99% of the
squamous cells, throughout the thickness of the
skin, show no maturity.
SYMPTOMS: Tend to occur on backs of hands or on
the face, lips, or ears.
SKIN-APPENDAGE TUMORS:
CYLINDROMA
SYRINGOMA
ECCRINE POROMA
TRICHOEPITHELIOMA
FIBROHISTIOCYTIC NEOPLASMS:
DERMATOFIBROMA:
ATYPICAL FIBROXANTHOMA:
KAPOSI SARCOMA:
MYCOSIS FUNGOIDES (PRIMARY CUTANEOUS T-CELL
LYMPHOMA):