Carlos Ricotti, M.D.

Clinical Assistant Professor | Department of Dermatology

Herbert Wertheim College of Medicine
Florida International University

DEPARTMENT OF DERMATOLOGY
LEARNING OBJECTIVES
⚫ Define the most common terms used in the field of dermatopathology,
and explain the importance of the terms

⚫ Recognize the most important histopathological patterns, and

understand the differences between them

⚫ Recognize the most important patterns of direct immunofluorescence

of the skin (e.g., bullous diseases, lupus erythematosus)

DEPARTMENT OF DERMATOLOGY
⚫ 1. Terminology

⚫ 2. Patterns of inflammation and neoplasia

⚫ 3. Immunofluorescence patterns

DEPARTMENT OF DERMATOLOGY
⚫ “MACROSCOPIC” used to described gross findings in
the skin visible to the naked eye

⚫ “MICROSCOPIC” used to describe findings in

histologic sections of diagnostic skin biopsies viewed
through the microscope.

DEPARTMENT OF DERMATOLOGY
⚫ Hyperkeratosis ⚫ Spongiosis
⚫ Orthokeratosis ⚫ Lentiginous
⚫ Parakeratosis ⚫ Epidermal atrophy
⚫ Dyskeratosis ⚫ Hypogranulosis
⚫ Acanthosis ⚫ Hypergranulosis
⚫ Papillomatosis ⚫ Liquefaction degeneration
⚫ Acantholysis ⚫ Pseudoepitheliomatous
hyperplasia

DEPARTMENT OF DERMATOLOGY
⚫ Increase in thickness of the
cornified layer (stratum
corneum) of the epidermis.

⚫ Often associated with a

qualitative abnormality of
the keratin.

DEPARTMENT OF DERMATOLOGY
⚫ Keratinization with absence of nuclei
in the stratum corneum. Compact
ortho(hyper)keratosis
⚫ Can be basket-weave, compact, or
lamellar.

basket-weave lamellar
orthokeratosis orthokeratosis

DEPARTMENT OF DERMATOLOGY
⚫ Abnormal Parakeratosis
keratinization
characterized by
retention of nuclei in
the stratum corneum.

DEPARTMENT OF DERMATOLOGY
⚫ Premature keratinization of individual cells or
groups of cells in the epidermis.

DEPARTMENT OF DERMATOLOGY
 Acanthosis: Epidermal hyperplasia
preferentially involving stratum spinosum.

Normal Skin

DEPARTMENT OF DERMATOLOGY
⚫ Thickening of the epidermis and dermis resulting in the formation
of exophytic, finger-like processes (papillae) as in a wart.

DEPARTMENT OF DERMATOLOGY
⚫ Loss of intercellular connections resulting in loss of cohesion between
keratinocytes in the epidermis. Not to be confused with “acanthosis”.

DEPARTMENT OF DERMATOLOGY
⚫ Intercellular edema of
the epidermis.

⚫ Results in attenuation of
the peripheral zone of
cytoplasm of adjacent
keratinocytes between
tight junctions
producing so-called
“intercellular bridges”.

DEPARTMENT OF DERMATOLOGY
⚫ A linear pattern
of melanocytic
proliferation in
the basal layer
of the
epidermis.

DEPARTMENT OF DERMATOLOGY
Thinning of the epidermis, usually accompanied by loss of the rete peg pattern.

DEPARTMENT OF DERMATOLOGY
 Hypogranulosis Hypergranulosis
⚫ Thinning or disappearance of the ⚫ Thickening of the granular layer
granular layer.

PSORIASIS LICHEN PLANUS

DEPARTMENT OF DERMATOLOGY
⚫ aka vacuolar alteration, consists of tiny spaces (vacuoles) in the basal
layer of the epidermis, typically seen in interface dermatitis.
⚫ Necrotic keratinocytes: dead keratinocytes which typically appear
anucleate and strongly eosinophilic (on H&E). May be seen in interface
dermatitis, irritant contact dermatitis, phototoxic dermatitis (eg sunburn).

vacuole

necrotic
keratinocytes

DEPARTMENT OF DERMATOLOGY
⚫ Aka pseudocarcinomatous hyperplasia. Irregular epidermal
hyperplasia that superficially resembles squamous cell carcinoma.

DEPARTMENT OF DERMATOLOGY
⚫ Dermal atrophy

⚫ Solar elastosis

⚫ Dermal edema

⚫ Pigment incontinence

⚫ Scar, sclerosis, fibrosis

⚫ Thrombosis

DEPARTMENT OF DERMATOLOGY
⚫ Thinning of the dermis, usually due mainly to reduction in the
amount of collagen.

Abnormal location of fat

due to atrophy of dermis

DEPARTMENT OF DERMATOLOGY
⚫ An age-related increase in (abnormal)
elastic fibers in the skin due to chronic
sun exposure, formerly known as
collagen basophilic degeneration, so-
called because of the blue-grey or
basophilic appearance of the dermis
on H&E stain.
⚫ Alternative terms include actinic
instead of solar, and elastoidosis
instead of elastosis.

DEPARTMENT OF DERMATOLOGY
⚫ Increased amount of fluid in
the extravascular space.
⚫ Recognized microscopically
as pallor of the dermis due to
increased space between
collagen fibers.

DEPARTMENT OF DERMATOLOGY
⚫ Loss of melanin pigment
from the epidermis into the
dermis, where it is usually
taken up by histiocytes
(macrophages), called
melanophages.

⚫ May be seen in melanocytic

neoplasia and certain
inflammatory processes.

melanophages

DEPARTMENT OF DERMATOLOGY
⚫ Fibrosis: generic term for the
formation of fibrous tissue.
⚫ Scar: fibrous tissue usually
formed after tissue injury as
part of the body’s repair
mechanism.
⚫ Sclerosis: fibrous tissue
consisting of collagen with
few fibroblasts.

DEPARTMENT OF DERMATOLOGY
⚫ Formation of blood clot within intact blood vessels, considered pathologic.
⚫ A thrombus may undergo propagation, embolization, dissolution,
organization and recanalization.

TROMBOANGITIS OBLITERANS

DEPARTMENT OF DERMATOLOGY
⚫ I. Terminology
⚫ II. Patterns of inflammation and neoplasia
⚫ III. Immunofluorescence patterns

DEPARTMENT OF DERMATOLOGY
a. Inflammatory
b. Neoplastic

DEPARTMENT OF DERMATOLOGY
⚫ Perivascular (+/- interstitial)
⚫ Interface
⚫ Spongiotic
⚫ Psoriasiform

⚫ Nodular and diffuse

⚫ Vasculitis
⚫ Vesicular (intra- and sub-epidermal)
⚫ Folliculitis
⚫ Panniculitis

DEPARTMENT OF DERMATOLOGY
⚫ Depth and distribution of the
inflammatory infiltrate.
⚫ Presence or absence of
epidermal changes.
⚫ Blood vessels, adnexa.

DEPARTMENT OF DERMATOLOGY
⚫ Depth:
✓ Superficial
✓ Superficial and deep (dermal)
✓ Subcutaneous (“panniculitis”)

⚫ Distribution
✓ Perivascular only.
✓ Perivascular and interstitial (“intervascular”).
✓ Lichenoid / patchy lichenoid (“band-like”).
✓ Nodular (large collections)
✓ Diffuse (sheet-like)
✓ Intra/perifollicular (“folliculitis”/ “perifolliculitis”)

DEPARTMENT OF DERMATOLOGY
⚫ None
⚫ Interface: vacuolar &/or lichenoid
⚫ Spongiosis
⚫ Psoriasiform (to irregular) acanthosis
⚫ Mixed
⚫ Vesicle formation

DEPARTMENT OF DERMATOLOGY
⚫ Higher power analysis of the composition of
the inflammatory infiltrate, and the presence
of other, disease specific findings:
examples…

DEPARTMENT OF DERMATOLOGY
⚫ Compact orthohyperkeratosis (as in LSC).
⚫ Parakeratosis (psoriasis, pityriasis rosea, guttate parapsoriasis).
⚫ Parakeratosis containing neutrophils (PLEVA, psoriasis, fungus,
seborrheic dermatitis).
⚫ Intraepidermal collections of eosinophils (urticarial BP).
⚫ Necrotic keratinocytes in the epidermis (EM, phototoxic
dermatitis, irritant contact dermatitis, toxic shock syndrome).
⚫ Pigment, e.g. hemosiderin, melanin, tattoo pigment.
⚫ Extravasated red blood cells (“bug bites”, pigmented purpura,
vasculitis).

DEPARTMENT OF DERMATOLOGY
⚫ Perivascular (+/- interstitial): fungus, insect bite, pigmented purpura
⚫ Interface: erythema multiforme, lichen planus
⚫ Spongiotic: acute contact dermatitis, nummular dermatitis, fungus
⚫ Psoriasiform: psoriasis, chronic contact dermatitis, fungus
⚫ Nodular and diffuse: lymphoma, “pseudolymphoma”
⚫ Small vessel vasculitis: leukocytoclastic vasculitis
⚫ Subepidermal vesicles: bullous pemphigoid, dermatitis herpetiformis
⚫ Panniculitis: erythema nodosum, erythema induratum

DIFFERENTIAL DIAGNOSIS OF EACH PATTERN IS DIFFERENT.

Rare diseases such as fungal infection may have more than one pattern. Also pattern may change as disease evolves;
e.g. allergic contact dermatitis is spongiotic when acute but may evolve into psoriasiform if it becomes chronic.

DEPARTMENT OF DERMATOLOGY
 Perivascular Pattern (+ Interstitial)

Pigmented purpuric dermatitis Schamberg’s dis. Fungus (tinea versicolor)

Deep gyrate erythema

Polymorphous light eruption

Stasis dermatitis

DEPARTMENT OF DERMATOLOGY
 Interface Pattern

Pityriasis lichenoides
Lichen planus

Interface dermatitis, vacuolar type,

necrotic keratocytes - Erythema multiforme

Lichen planus-like keratosis

Fixed drug eruption
(patchy lichenoid)

DEPARTMENT OF DERMATOLOGY
 Spongiotic Pattern
⚫ Spongiotic dermatitis,
with intraepidermal
vesicles.
⚫ Histologic differential
diagnosis includes:
✓ acute allergic contact
dermatitis
✓ insect bite
✓ urticarial stage of bullous
pemphigoid.

Spongiotic dermatitis ⚫ Clinical history is

necessary for a
definitive diagnosis in
such a case.
Eosinophilic spongiosis

DEPARTMENT OF DERMATOLOGY
 Psoriasiform

Psoriasiform, with coarse collagen in the dermis in “vertical” streaks.

Diagnosis: Lichen simplex chronicus

DEPARTMENT OF DERMATOLOGY
⚫ Inflammatory dermatoses may present as acute or chronic
depending on the time course of the disease process. In general:

✓ Acute: evolve rapidly

➢In general, develop over hours to days.
➢Last days to 6 weeks.

✓ Chronic: evolve slowly

➢More than 6 weeks: In general last months to years
Some may even persist for life

DEPARTMENT OF DERMATOLOGY
⚫ Is there any correlation between clinical presentation and
histology?
⚫ To some extent, yes.
✓ Spongiosis, dermal edema, necrotic keratinocytes ➔ ACUTE
✓ Hyperkeratosis, acanthosis, fibrosis ➔ CHRONIC
EXAMPLES:

ACUTE: Urticaria, Acute eczematous dermatitis, Erythema Multiforme.

CHRONIC: Psoriasis, Lichen Planus, Lichen Simplex Chronicus

DEPARTMENT OF DERMATOLOGY
⚫ A “dermal hypersensitivity reaction” ⚫ Microscopic (biopsy) findings
⚫ Diverse etiologies ✓ Dermal edema
⚫ IgE mediated mast cell ✓ Sparse perivascular and interstitial mixed
degranulation, manifesting as inflammatory cell infiltrate (lymphocytes,
transient wheals. neutrophils, eosinophils)
✓ No epidermal changes

DEPARTMENT OF DERMATOLOGY
⚫ Allergic contact dermatitis, atopic dermatitis, certain ⚫ Microscopic (biopsy) findings:
types of photodermatitis, irritant contact dermatitis Spongiosis; Perivascular infiltrate of
that present as pruritic, edematous, oozing papules lymphocytes and often eosinophils
and plaques, often with vesicles and bullae, that
may become chronic.

POISON IVY DERMATITIS

DEPARTMENT OF DERMATOLOGY
⚫ A “multiform” eruption with characteristic “targetoid” lesions that may be associated with certain
infections (Herpes simplex, mycoplasmas, certain fungi) or drugs (sulfonamides, penicillin, NSAIDs)

⚫ Microscopic findings: Lymphocytic infiltrate in the superficial dermis that extends into the epidermis
(“interface” dermatitis”) + necrotic keratinocytes in the epidermis. In severe cases, the entire epidermis
may become necrotic.

DEPARTMENT OF DERMATOLOGY
⚫ A chronic condition that presents as
⚫ Microscopic findings
scaly plaques with a predilection for
✓ The classic “psoriasiform” dermatitis:
the extensor surfaces, scalp.
➢Psoriasiform epidermal hyperplasia
➢Confluent parakeratosis containing
neutrophils

DEPARTMENT OF DERMATOLOGY
 ⚫ Microscopic findings
⚫ Idiopathic eruption
of pruritic, flat- ✓ Dense, band-like (“lichenoid”) infiltrate
of lymphocytes at the epidermal-
topped papules with dermal junction
a predilection for ✓ Epidermal hyperplasia (not
the flexor surfaces of psoriasiform) with altered shape of the
the wrists but may rete pegs (“saw-toothing”), necrotic
involve other keratinocytes, hyperkeratosis and
anatomic sites. hypergranulosis.

DEPARTMENT OF DERMATOLOGY
⚫ Circumscribed pruritic plaques of ⚫ Microscopic findings
lichenified (thickened) skin, caused ✓ Psoriasiform dermatitis
✓ Thickened, hyperkeratotic epidermis
by repetitive rubbing and scratching.
✓ Thickened fibrotic dermis

DEPARTMENT OF DERMATOLOGY
⚫ Premalignant lesions.
⚫ Histologic approach to cutaneous neoplasms.
⚫ Selection of cutaneous neoplasms.

DEPARTMENT OF DERMATOLOGY
⚫ Usually take the form of an intraepithelial proliferation of cytologically
atypical cells.
⚫ Non-invasive; no capacity to metastasize.
⚫ Cytologic atypia manifests mainly as nuclear changes, such as
enlargement, altered shape, altered chromatin pattern, nucleoli etc.
⚫ Other features: increased mitoses, abnormal mitoses, necrotic cells.
⚫ EXAMPLES (common premalignancies):
✓ Actinic keratosis
✓ Bowen’s disease (squamous cell carcinoma-in-situ)
✓ Melanoma-in-situ

DEPARTMENT OF DERMATOLOGY
⚫ A premalignant
epidermal lesion.
Parakeratosis
⚫ Gross lesions are
crusted, often
inconspicuous.
⚫ Microscopically
characterized by
abnormal
keratinization of the
epidermis and atypia
of epidermal
keratinocytes in the
lower portion of the Abnormal keratinocyte
epidermis. population in basal
aspect of epidermis

DEPARTMENT OF DERMATOLOGY
 ⚫ Microscopically characterized by aypia of epidermal
Left Forehead keratocytes in all levels of the epidermis.

DEPARTMENT OF DERMATOLOGY
 ⚫ Microscopically characterized by a
haphazard proliferation of atypical
melanocytes within the epidermis.

DEPARTMENT OF DERMATOLOGY
 MORE SKIN
NEOPLASIAS WILL BE
SEEN IN THE MOST
COMMON SKIN
TUMORS CLASS

DEPARTMENT OF DERMATOLOGY
⚫ Direct immunofluorescence (DIF) is a laboratory technique for
demonstrating immunoglobulin (Ig) and complement in the skin.
⚫ Used as an adjunctive technique to confirm the diagnosis in certain
diseases known to be immunologically mediated.
⚫ Employs fluorescent-tagged antibodies to the target molecules
(Ig/complement), whose localization in the tissue can then be
visualized using a fluorescent microscope.
⚫ Typically used in certain vesicobullous diseases and sometimes in
cases of vasculitis.
⚫ Allows the determination of both the location, pattern, and
composition of deposits in skin biopsies.

DEPARTMENT OF DERMATOLOGY
⚫ Routinely employed in the diagnosis of “immunobullous” diseases such as:
✓ Bullous pemphigoid (subepidermal vesicles)
✓ Epidermolysis bullosa acquisita (subepidermal vesicles)
✓ Lupus erythematosus (subepidermal vesicles)
✓ Pemphigus (intraepidermal vesicles with acantholysis)
✓ Dermatitis herpetiformis (subepidermal vesicles)
✓ Linear IgA bullous dermatosis (subepidermal vesicles)

SOME OF THESE DISEASES MAY BE DIFFICULT TO DISTINGUISH FROM EACH

OTHER BY ROUTINE MICROSCOPY DUE TO SIMILAR OR OVERLAPPING
HISTOPATHOLOGY, MAKING DIF ESSENTIAL FOR ACCURATE DIAGNOSIS.

DEPARTMENT OF DERMATOLOGY
Typically includes Ig class (G, A, M, D, E), complement and
pattern of deposits (location, quality).
Examples of patterns reported:
Linear BMZ*
Granular BMZ
Intercellular (epidermal)
Dermal papillary
Vascular/perivascular

*BMZ = basement membrane zone

DEPARTMENT OF DERMATOLOGY
 acantholysis SUPERFICIAL TYPE
⚫ Caused by deposition of
DEEP TYPE

immunoglobulin and complement in

the epidermis in an “intercellular”
fashion, resulting in loss of keratinocyte
cohesion (“acantholysis”) and
subsequent blister formation.
⚫ May involve mucous membranes as
well as skin.

DIF: “Chicken
wire” pattern
of intercellular
immunoglobu
lin and
complement
in the
Blisters rupture easily resulting in epidermis.
crusting and erosions

DEPARTMENT OF DERMATOLOGY
⚫ Caused by linear basal
keratinocyte
deposition of Ig and SITE OF CLEFT
complement in the FORMATION IN
subepidermal BULLOUS
PEMPHIGOID
lamina lucida
basement membrane
lamina densa
zone. SUBEPIDERMAL
dermis
⚫ May involve mucous
BLISTER

membranes as well as
skin. DIF: Linear
deposition of
immunoglobulin
(IgG) and
complement in
the
subepidermal
Tense fluid-filled blisters of BP basement
membrane
zone.

DEPARTMENT OF DERMATOLOGY
⚫ Associated with sensitivity to dietary SITE OF CLEFT
basal FORMATION IN
gluten and celiac disease. keratinocyte DERMATITIS
HERPETIFORMIS
⚫ Intensely pruritic lesions with a
predilection for the extensor surfaces Early: split above
Microabscesses
at the tips of
of the extremities, buttocks, scalp, lamina lucida lamina lucida.
dermal papillae
nuchal area. lamina densa
⚫ IgA deposits in the papillary dermis. dermis Late: lamina Subepidermal
densa destroyed. blisters.

DIF: Granular
deposits of
immunoglobulin
(IgA) at the tips
of dermal
papillae.

DEPARTMENT OF DERMATOLOGY
MORE EXAMPLES OF DIRECT
IMMUNOFLUORESCENCE
WILL BE SEEN IN THE
BLISTERING DISEASES AND
COLLAGEN DISEASES
CLASSES

DEPARTMENT OF DERMATOLOGY
Dermatology
DEPARTMENT OF DERMATOLOGY