Inflammatory skin disease everypathologist should know
Steven D. BillingsCleveland [email protected]
General Concepts⢠Pattern recognition
â Epidermal predominant vs. dermal predominant⢠Epidermal changes trump dermal changes
â Distribution of the inflammatory infiltrate⢠Superficial vs. superficial and deep⢠Location: perivascular, interstitial, nodular
â Nature of inflammatory infiltrate⢠Mononuclear (lymphocytes and histiocytes)⢠Mixed (mononuclear and granulocytes)⢠Granulocytic
⢠Correlation with clinical presentation⢠Never diagnose âchronic nonspecific dermatitisâ
⢠Pattern recognitionâ Epidermal predominant vs. dermal predominant
⢠Epidermal changes trump dermal changesâ Distribution of the inflammatory infiltrate
⢠Superficial vs. superficial and deep⢠Location: perivascular, interstitial, nodular
â Nature of inflammatory infiltrate⢠Mononuclear (lymphocytes and histiocytes)⢠Mixed (mononuclear and granulocytes)⢠Granulocytic
⢠Correlation with clinical presentation⢠Never diagnose âchronic nonspecific dermatitisâ
Principle Patterns:Epidermal Changes Predominant
⢠Spongiotic pattern⢠Psoriasiform pattern
â Spongiotic and psoriasiform often co-exist⢠Interface pattern
â Basal vacuolization⢠Perivascular infiltrate
or⢠Lichenoid infiltrate
⢠Spongiotic pattern⢠Psoriasiform pattern
â Spongiotic and psoriasiform often co-exist⢠Interface pattern
â Basal vacuolization⢠Perivascular infiltrate
or⢠Lichenoid infiltrate
Principle Patterns:Dermal Changes Predominant
⢠Superficial perivascular⢠Superficial and deep perivascular⢠Interstitial pattern
â Palisading granulomatousâ Nodular and diffuse
⢠Sclerosing pattern
⢠Panniculitis⢠Bullous disease⢠Miscellaneous
⢠Superficial perivascular⢠Superficial and deep perivascular⢠Interstitial pattern
â Palisading granulomatousâ Nodular and diffuse
⢠Sclerosing pattern
⢠Panniculitis⢠Bullous disease⢠Miscellaneous
Spongiotic Dermatitis
⢠Three phasesâ Acuteâ Subacuteâ Chronic
⢠Different but overlapping histologicfeatures
⢠Three phasesâ Acuteâ Subacuteâ Chronic
⢠Different but overlapping histologicfeatures
Spongiotic Dermatitis
⢠Acute spongiotic dermatitisâ Normal âbasket-weaveâ stratum corneumâ Pale keratinocytesâ Spongiosisâ Spongiotic vesicles (variable)â Papillary dermal edemaâ Variable superficial perivascular infiltrate of
lymphocytes often with some eosinophilsâ Rarely biopsied in acute phase
⢠Acute spongiotic dermatitisâ Normal âbasket-weaveâ stratum corneumâ Pale keratinocytesâ Spongiosisâ Spongiotic vesicles (variable)â Papillary dermal edemaâ Variable superficial perivascular infiltrate of
lymphocytes often with some eosinophilsâ Rarely biopsied in acute phase
Spongiotic Dermatitis
⢠Subacute spongiotic dermatitisâ Parakeratosis often with serum (wet scale)â Diminished granular layerâ Spongiosisâ Acanthosis (overlap with psoriasiform pattern)â Variable superficial perivascular infiltrate of
lymphocytes often with some eosinophilsâ Less edema
⢠Subacute spongiotic dermatitisâ Parakeratosis often with serum (wet scale)â Diminished granular layerâ Spongiosisâ Acanthosis (overlap with psoriasiform pattern)â Variable superficial perivascular infiltrate of
lymphocytes often with some eosinophilsâ Less edema
Spongiotic Dermatitis
⢠Chronic spongiotic dermatitisâ Hyperkeratosisâ Parakeratosisâ Irregular granular layerâ Acanthosis (overlap with psoriasiform)â Minimal to mild spongiosisâ Variable perivascular infiltrate, often with
eosinophilsâ Dermis may be fibrotic
⢠Chronic spongiotic dermatitisâ Hyperkeratosisâ Parakeratosisâ Irregular granular layerâ Acanthosis (overlap with psoriasiform)â Minimal to mild spongiosisâ Variable perivascular infiltrate, often with
eosinophilsâ Dermis may be fibrotic
Common Clinical Types ofSpongiotic Dermatitis
⢠Eczema Dermatitis Familyâ Atopic dermatitisâ Contact dermatitisâ Nummular dermatitisâ Dyshidrotic dermatitis (hand/foot dermatitis)â Id reaction (autoeczematization)â Eczematous drug eruption
⢠Eczema Dermatitis Familyâ Atopic dermatitisâ Contact dermatitisâ Nummular dermatitisâ Dyshidrotic dermatitis (hand/foot dermatitis)â Id reaction (autoeczematization)â Eczematous drug eruption
Eczema
⢠Clinical term⢠Histologically spongiotic dermatitis⢠Specific diagnosis dependent on
correlation with clinical presentation
⢠CLINICAL SUBTYPES AREHISTOLOGICALLY INDISTINGUISHABLE
⢠Clinical term⢠Histologically spongiotic dermatitis⢠Specific diagnosis dependent on
correlation with clinical presentation
⢠CLINICAL SUBTYPES AREHISTOLOGICALLY INDISTINGUISHABLE
Allergic Contact Dermatitis⢠Clinical
â Erythematous papules, plaques and sometimesvesicles
â May have linear patternâ Secondary to type IV delayed hypersensitivity
reactionâ Examples: nickel allergy, poison ivy
⢠Microscopicâ Typical spongiotic dermatitisâ May have Langerhans cell microabscesses
⢠Clinicalâ Erythematous papules, plaques and sometimes
vesiclesâ May have linear patternâ Secondary to type IV delayed hypersensitivity
reactionâ Examples: nickel allergy, poison ivy
⢠Microscopicâ Typical spongiotic dermatitisâ May have Langerhans cell microabscesses
Nummular Dermatitis⢠Common form of eczema that is biopsied⢠Clinical
â Pruritic round to oval patches and plaquesâ Often on extremities
⢠Microscopicâ Psoriasiform and spongioticâ Can be classified as psoriasiform dermatitis
⢠Differential diagnosisâ Psoriasis
⢠Common form of eczema that is biopsied⢠Clinical
â Pruritic round to oval patches and plaquesâ Often on extremities
⢠Microscopicâ Psoriasiform and spongioticâ Can be classified as psoriasiform dermatitis
⢠Differential diagnosisâ Psoriasis
Practical Tips for Eczematous Dermatitis
⢠Dx: âspongiotic dermatitis, see noteâ⢠(Dx in cases with acanthosis: âspongiotic
psoriasiform dermatitis, see noteâ)⢠Note: âThe histologic features are compatible
with an eczematous dermatitis. The DDx couldincludeâŚ.. Clinicopathologic correlation isrecommended.â
⢠Tipsâ Eliminate where possible more specific entitiesâ Neutrophils in stratum corneum or epidermis: exclude
dermatophytosis or psoriasisâ Clinical history can be helpfulâ Langerhans cell microabscess: suggest contact
dermatitis
⢠Dx: âspongiotic dermatitis, see noteâ⢠(Dx in cases with acanthosis: âspongiotic
psoriasiform dermatitis, see noteâ)⢠Note: âThe histologic features are compatible
with an eczematous dermatitis. The DDx couldincludeâŚ.. Clinicopathologic correlation isrecommended.â
⢠Tipsâ Eliminate where possible more specific entitiesâ Neutrophils in stratum corneum or epidermis: exclude
dermatophytosis or psoriasisâ Clinical history can be helpfulâ Langerhans cell microabscess: suggest contact
dermatitis
Stasis Dermatitis⢠Clinical
â Lower extremities associated with venousinsufficiency
â May develop ulcers⢠Microscopic
â Subacute to chronic spongiotic dermatitisâ Variable acanthosisâ Lobular proliferation of thick-walled dermal vesselsâ Extravasated erythrocytes, siderophages,
perivascular lymphocytesâ Variable dermal fibrosis
⢠Clinicalâ Lower extremities associated with venous
insufficiencyâ May develop ulcers
⢠Microscopicâ Subacute to chronic spongiotic dermatitisâ Variable acanthosisâ Lobular proliferation of thick-walled dermal vesselsâ Extravasated erythrocytes, siderophages,
perivascular lymphocytesâ Variable dermal fibrosis
⢠37 cases of stasis dermatitis presenting assolitary lesion
⢠33/37 no history of venous stasis⢠33% mistaken for SCC; 24% mistaken for
BCC
⢠37 cases of stasis dermatitis presenting assolitary lesion
⢠33/37 no history of venous stasis⢠33% mistaken for SCC; 24% mistaken for
BCC
J Am Acad Dermatol 2009;61: 1028-32
Stasis Dermatitis⢠Differential diagnosis
â Eczematous dermatitisâ Kaposi sarcoma (acroangiodermatitis)
⢠Tipsâ High index of suspicionâ Vascular changes key featureâ Sometimes clinically mimics neoplasm: consider
deeper levelsâ Can have other form of eczematous dermatitis on
stasis background (descriptive dx: spongioticdermatitis and stasis change)
⢠Differential diagnosisâ Eczematous dermatitisâ Kaposi sarcoma (acroangiodermatitis)
⢠Tipsâ High index of suspicionâ Vascular changes key featureâ Sometimes clinically mimics neoplasm: consider
deeper levelsâ Can have other form of eczematous dermatitis on
stasis background (descriptive dx: spongioticdermatitis and stasis change)
PsoriasisPsoriasis vulgaris⢠Clinical
â Usually presents in2nd-3rd decades
â Erythematous plaqueswith silvery scale
â Extensor surfaces,scalp, gluteal cleft,glans penis
â Nail pitting and yellowdiscoloration
â Arthritis 1-5%
Psoriasis vulgaris⢠Clinical
â Usually presents in2nd-3rd decades
â Erythematous plaqueswith silvery scale
â Extensor surfaces,scalp, gluteal cleft,glans penis
â Nail pitting and yellowdiscoloration
â Arthritis 1-5%
Psoriasis Vulgaris
⢠Microscopicâ Uniform acanthosis with elongated rete ridgesâ Absent (diminished) granular layerâ Prominent parakeratosis (dry scale)â Neutrophils in stratum corneum (Munroâs
microabscess) and/or epidermis (pustules of Kogoj)â Suprapapillary plate thinningâ Dilated, tortuous papillary dermal vesselsâ No eosinophils
⢠Microscopicâ Uniform acanthosis with elongated rete ridgesâ Absent (diminished) granular layerâ Prominent parakeratosis (dry scale)â Neutrophils in stratum corneum (Munroâs
microabscess) and/or epidermis (pustules of Kogoj)â Suprapapillary plate thinningâ Dilated, tortuous papillary dermal vesselsâ No eosinophils
Partially treated psoriasis
Psoriasis Vulgaris
⢠Differential Diagnosisâ Nummular dermatitis
⢠Spongiosis, wet scale, often has eosinophilsâ Contact dermatitis
⢠Spongiosis, wet scale, often has eosinophils,Langerhans cell microabscesses (+/-)
â Dermatophytosisâ Drug-induced psoriasis
⢠Differential Diagnosisâ Nummular dermatitis
⢠Spongiosis, wet scale, often has eosinophilsâ Contact dermatitis
⢠Spongiosis, wet scale, often has eosinophils,Langerhans cell microabscesses (+/-)
â Dermatophytosisâ Drug-induced psoriasis
Dermatophytosis
⢠Clinicalâ Annular scaly plaques
with central clearingâ Usually on trunk
⢠Clinicalâ Annular scaly plaques
with central clearingâ Usually on trunk
Dermatophytosis
⢠Microscopicâ Neutrophils in stratum corneumâ Parakeratosisâ Hyphae in stratum corneum (usually seen
with PAS or GMS stain)â Acanthosisâ Variable spongiosisâ Superficial perivascular infiltrate often with
some eosinophils
⢠Microscopicâ Neutrophils in stratum corneumâ Parakeratosisâ Hyphae in stratum corneum (usually seen
with PAS or GMS stain)â Acanthosisâ Variable spongiosisâ Superficial perivascular infiltrate often with
some eosinophils
Dermatophytosis
⢠Tips:â Neutrophils may be absent in lesions treated
with topical steroidsâ Always get PAS or GMS stains if clinical
history is ârash not responsive to topicalsteroidsâ
â Look for fungi adjacent to neutrophils
⢠Tips:â Neutrophils may be absent in lesions treated
with topical steroidsâ Always get PAS or GMS stains if clinical
history is ârash not responsive to topicalsteroidsâ
â Look for fungi adjacent to neutrophils
Drug-Induced Psoriasis
⢠Tumor necrosis factor-ι (TNF-ι) inhibitorscan cause psoriasis-like rash
⢠Most commonly seen in patients withinflammatory bowel disease on TNF-ιinhibitors
⢠Looks like psoriasis vulgaris except witheosinophils in the dermis
⢠Tumor necrosis factor-ι (TNF-ι) inhibitorscan cause psoriasis-like rash
⢠Most commonly seen in patients withinflammatory bowel disease on TNF-ιinhibitors
⢠Looks like psoriasis vulgaris except witheosinophils in the dermis
34-year-old womanwith Crohnâs disease
Presented witherythematous plaquesinvolving vulva
Clinical diagnosis:cutaneous Crohnâsdisease
Presented witherythematous plaquesinvolving vulva
Clinical diagnosis:cutaneous Crohnâsdisease
Psoriasis Vulgaris⢠Practical tips
â Eosinophils absent in psoriasis (except drug-induced; intravascular eosinophils donâtcount)
â Epidermal hyperplasia not always uniformâ Impetiginization not seenâ Some features may be absent in partially
treated psoriasisâ Descriptive dx: psoriasiform dermatitis
⢠Practical tipsâ Eosinophils absent in psoriasis (except drug-
induced; intravascular eosinophils donâtcount)
â Epidermal hyperplasia not always uniformâ Impetiginization not seenâ Some features may be absent in partially
treated psoriasisâ Descriptive dx: psoriasiform dermatitis
Guttate Psoriasis⢠Clinical
â Rapid onsetâ Widespread diseaseâ Small scaly plaquesâ Antecedent streptococcal infection
⢠Microscopicâ Minimal acanthosisâ Diminished granular layer (variable)â Focal mounds of parakeratosis with neutrophils
(sometimes neutrophils absent)⢠Differential Diagnosis
â Pityriasis rosea, dermatophyte infection
⢠Clinicalâ Rapid onsetâ Widespread diseaseâ Small scaly plaquesâ Antecedent streptococcal infection
⢠Microscopicâ Minimal acanthosisâ Diminished granular layer (variable)â Focal mounds of parakeratosis with neutrophils
(sometimes neutrophils absent)⢠Differential Diagnosis
â Pityriasis rosea, dermatophyte infection
Guttate Psoriasis
⢠Practical tipsâ Clinical history
⢠Rapid onset⢠Antecedent streptococcal infection 2/3
â Neutrophils not always present⢠Descriptive diagnosis: Psoriasiform or spongiotic
dermatitis, see note⢠Note: The mounds of parakeratosis suggest the
possibilities of guttate psoriasis or pityriasis rosea
⢠Practical tipsâ Clinical history
⢠Rapid onset⢠Antecedent streptococcal infection 2/3
â Neutrophils not always present⢠Descriptive diagnosis: Psoriasiform or spongiotic
dermatitis, see note⢠Note: The mounds of parakeratosis suggest the
possibilities of guttate psoriasis or pityriasis rosea
Lichen Simplex Chronicus andPrurigo Nodularis
⢠Clinicalâ Spectrum of same dermatologic diseaseâ Secondary to persistent rubbing/scratchingâ Lichen simplex chronicus presents as pruritic
indurated plaquesâ Prurigo nodularis presents as pruritic nodulesâ Lesions occur only where the skin can be reached:
posterior scalp, ankle, shin, forearm, anterior thigh,genitalia
â Can develop as a secondary change in underlyingdermatitis
⢠Clinicalâ Spectrum of same dermatologic diseaseâ Secondary to persistent rubbing/scratchingâ Lichen simplex chronicus presents as pruritic
indurated plaquesâ Prurigo nodularis presents as pruritic nodulesâ Lesions occur only where the skin can be reached:
posterior scalp, ankle, shin, forearm, anterior thigh,genitalia
â Can develop as a secondary change in underlyingdermatitis
Lichen Simplex Chronicus andPrurigo Nodularis
⢠Microscopic:â Prominent compact hyperkeratosisâ Variable parakeratosisâ Thickened granular layerâ Acanthosis, sometimes with
pseudoepitheliomatous patternâ Vertical fibrosis of papillary dermisâ Mild perivascular lymphocytic infiltrateâ Looks like acral skin (hairy palm sign)
⢠Microscopic:â Prominent compact hyperkeratosisâ Variable parakeratosisâ Thickened granular layerâ Acanthosis, sometimes with
pseudoepitheliomatous patternâ Vertical fibrosis of papillary dermisâ Mild perivascular lymphocytic infiltrateâ Looks like acral skin (hairy palm sign)
Practical Tips
⢠Acral skin in non-acral location⢠âHairy palmâ sign⢠Clinical history: is it itchy?⢠Descriptive diagnosis
â Psoriasiform dermatitis with f/o LSC/PN⢠May be superimposed on chronic
spongiotic dermatitisâ Spongiotic dermatitis with superimposed
features of LSC
⢠Acral skin in non-acral location⢠âHairy palmâ sign⢠Clinical history: is it itchy?⢠Descriptive diagnosis
â Psoriasiform dermatitis with f/o LSC/PN⢠May be superimposed on chronic
spongiotic dermatitisâ Spongiotic dermatitis with superimposed
features of LSC
Lichen Planus⢠Clinical
â Pruritic violaceous,polygonal papules
â Predilection forflexural surfaces ofwrists and ankles
â May be widespreadâ Oral: lace-like
pattern
⢠Clinicalâ Pruritic violaceous,
polygonal papulesâ Predilection for
flexural surfaces ofwrists and ankles
â May be widespreadâ Oral: lace-like
pattern
Lichen Planus
⢠Microscopic featuresâ Hyperkeratosis without parakeratosisâ Acanthosis with wedge-shaped
hypergranulosisâ Interface change with dense band-like
lymphocytic infiltrate (rare eosinophilsacceptable)
â âSaw-toothâ rete pegsâ Scattered dyskeratotic cells
⢠Microscopic featuresâ Hyperkeratosis without parakeratosisâ Acanthosis with wedge-shaped
hypergranulosisâ Interface change with dense band-like
lymphocytic infiltrate (rare eosinophilsacceptable)
â âSaw-toothâ rete pegsâ Scattered dyskeratotic cells
Oral LichenPlanus⢠Absent or subtle
granular layer⢠Parakeratosis⢠Lichenoid infiltrate
(sometimes lessprominent)
⢠âSaw-toothingâ notusually present
⢠Absent or subtlegranular layer
⢠Parakeratosis⢠Lichenoid infiltrate
(sometimes lessprominent)
⢠âSaw-toothingâ notusually present
Lichen Planus
⢠Differential Diagnosisâ Lichenoid benign keratosisâ Lichenoid drug eruptionâ Lichenoid graft vs. host diseaseâ Lupus erythematosusâ Early lichen sclerosus
⢠Differential Diagnosisâ Lichenoid benign keratosisâ Lichenoid drug eruptionâ Lichenoid graft vs. host diseaseâ Lupus erythematosusâ Early lichen sclerosus
Lichenoid Benign Keratosis
⢠Solitary lesion⢠Usually on trunk⢠Middle-aged and older patients⢠Clinically confused with basal cell
carcinoma⢠Looks like lichen planus or benign
keratosis with lichenoid infiltrate
⢠Solitary lesion⢠Usually on trunk⢠Middle-aged and older patients⢠Clinically confused with basal cell
carcinoma⢠Looks like lichen planus or benign
keratosis with lichenoid infiltrate
Lichenoid DrugEruption
⢠Widespreadviolaceous papules
⢠May occur weeksto months afterinitiation of drugtherapy
⢠May progress toexfoliativedermatitis
⢠Widespreadviolaceous papules
⢠May occur weeksto months afterinitiation of drugtherapy
⢠May progress toexfoliativedermatitis
Lichenoid Drug Eruption
⢠Microscopicâ Very similar to lichen planusâ Occasional to frequent eosinophilsâ Often some parakeratosis
⢠Differential Diagnosisâ Lichen planus, fixed drug eruption
⢠Practical tipsâ Look for eosinophils and parakeratosis
⢠Microscopicâ Very similar to lichen planusâ Occasional to frequent eosinophilsâ Often some parakeratosis
⢠Differential Diagnosisâ Lichen planus, fixed drug eruption
⢠Practical tipsâ Look for eosinophils and parakeratosis
Lichen Sclerosus
⢠Early lesions:â Lichenoid infiltrate of lymphocytes and plasma
cells with interface changeâ Psoriasiform epidermal hyperplasia may be
present earlyâ Basement membrane thickening may be
presentâ Look for evidence of papillary dermal fibrosis
⢠Early lesions:â Lichenoid infiltrate of lymphocytes and plasma
cells with interface changeâ Psoriasiform epidermal hyperplasia may be
present earlyâ Basement membrane thickening may be
presentâ Look for evidence of papillary dermal fibrosis
Lichen Sclerosus⢠Established lesions
â Homogenized orsclerotic papillarydermis
â Scattered lymphocytesand plasma cellsbeneath alteredcollagen
â Atrophic epidermiswith compacthyperkeratosis andthickened granularlayer
⢠Established lesionsâ Homogenized or
sclerotic papillarydermis
â Scattered lymphocytesand plasma cellsbeneath alteredcollagen
â Atrophic epidermiswith compacthyperkeratosis andthickened granularlayer
Practical Tips⢠Rare eosinophils acceptable in lichen planus
â If numerous think lichenoid drug reaction⢠Parakeratosis typically absent in lichen planus
â Exception: oral lichen planus⢠Solitary lesions that look like lichen planus:
lichenoid benign keratosis⢠Looks like lichen planus on genital skin:
â Lichenoid interface dermatitis, see commentâ Comment: the differential diagnosis includes lichen
planus vs. early lichen sclerosus
⢠Rare eosinophils acceptable in lichen planusâ If numerous think lichenoid drug reaction
⢠Parakeratosis typically absent in lichen planusâ Exception: oral lichen planus
⢠Solitary lesions that look like lichen planus:lichenoid benign keratosis
⢠Looks like lichen planus on genital skin:â Lichenoid interface dermatitis, see commentâ Comment: the differential diagnosis includes lichen
planus vs. early lichen sclerosus
Erythema multiforme spectrum⢠Erythema multiforme
â Self-limiting episodic eruptionsâ Erythematous macules, papules and targetoid
lesionsâ Extensor surfaces, palms, soles, and oral
mucosaâ Associated with HSV, Mycoplasma, and drugs
(sulfonamides)⢠Stevens-Johnson syndrome: mucosal
involvement <10% body surface area
⢠Erythema multiformeâ Self-limiting episodic eruptionsâ Erythematous macules, papules and targetoid
lesionsâ Extensor surfaces, palms, soles, and oral
mucosaâ Associated with HSV, Mycoplasma, and drugs
(sulfonamides)⢠Stevens-Johnson syndrome: mucosal
involvement <10% body surface area
Clinical Features
⢠Toxic epidermal necrolysis (TEN)â Widespread tender macular erythematous eruption
with vesicles and bullae >30% body surface areaâ Associated with drugsâ Mortality 25-50%
⢠Stevens Johnson-TEN overlap: 10-30%body surface area
⢠Toxic epidermal necrolysis (TEN)â Widespread tender macular erythematous eruption
with vesicles and bullae >30% body surface areaâ Associated with drugsâ Mortality 25-50%
⢠Stevens Johnson-TEN overlap: 10-30%body surface area
Erythema Multiforme/TEN⢠Microscopic
â Normal basket-weave stratum corneumâ Spongiosisâ Dyskeratotic cells at all levels of epidermisâ Basal vacuolizationâ Mild superficial perivascular lymphohistiocytic infiltrate
(sometimes eosinophils)â Exocytosis of lymphocytesâ Epidermal necrosis (seen in older lesions)
⢠More common in TEN
⢠Microscopicâ Normal basket-weave stratum corneumâ Spongiosisâ Dyskeratotic cells at all levels of epidermisâ Basal vacuolizationâ Mild superficial perivascular lymphohistiocytic infiltrate
(sometimes eosinophils)â Exocytosis of lymphocytesâ Epidermal necrosis (seen in older lesions)
⢠More common in TEN
Differential Diagnosis
⢠Lupus erythematosus/dermatomyositisâ More epidermal change
⢠Morbilliform drug eruptionâ Less epidermal damage
⢠Graft versus host diseaseâ Clinical history
⢠Lupus erythematosus/dermatomyositisâ More epidermal change
⢠Morbilliform drug eruptionâ Less epidermal damage
⢠Graft versus host diseaseâ Clinical history
Practical Tips: EM and TEN⢠Necrotic keratinocytes, normal stratum
corneum⢠Disproportionate epidermal damage for
amount of inflammation⢠Histologic distinction between EM and
TEN requires clinical information⢠SJS and TEN: medical emergency⢠TEN clinical ddx: Staph scalded skin
syndrome
⢠Necrotic keratinocytes, normal stratumcorneum
⢠Disproportionate epidermal damage foramount of inflammation
⢠Histologic distinction between EM andTEN requires clinical information
⢠SJS and TEN: medical emergency⢠TEN clinical ddx: Staph scalded skin
syndrome
Staph scalded skin syndrome
Lupus Erythematosus⢠Clinical
â Chronic (discoid)⢠Well-demarcated scaly plaques⢠Erythematous to hyper or hypopigmented⢠Usually on head/neck (sun-exposed skin)⢠Most patients with skin only disease
â Subacute⢠Scaly erythematous, often annular plaques⢠Upper trunk, extensor surfaces of arms⢠Positive ANA 75%
⢠Clinicalâ Chronic (discoid)
⢠Well-demarcated scaly plaques⢠Erythematous to hyper or hypopigmented⢠Usually on head/neck (sun-exposed skin)⢠Most patients with skin only disease
â Subacute⢠Scaly erythematous, often annular plaques⢠Upper trunk, extensor surfaces of arms⢠Positive ANA 75%
Lupus Erythematosus
⢠Clinicalâ Acute
⢠Associated with systemic lupus erythematosus⢠Erythematous lesions⢠Malar rash⢠Positive ANA and anti-DNA antibodies
⢠Clinicalâ Acute
⢠Associated with systemic lupus erythematosus⢠Erythematous lesions⢠Malar rash⢠Positive ANA and anti-DNA antibodies
Lupus Erythematosus⢠Microscopic
â Histologic overlap between subtypesâ Basal vacuolizationâ Perivascular and periadnexal mononuclear cell
infiltrateâ Epidermal atrophy (often)â Thickened basement membrane (often)â Increased dermal mucinâ Follicular plugging (often)â May have reactive squamous atypia (AK clue)
⢠Microscopicâ Histologic overlap between subtypesâ Basal vacuolizationâ Perivascular and periadnexal mononuclear cell
infiltrateâ Epidermal atrophy (often)â Thickened basement membrane (often)â Increased dermal mucinâ Follicular plugging (often)â May have reactive squamous atypia (AK clue)
Lupus Erythematosus
⢠Differential diagnosisâ Dermatomyositisâ Lichen planusâ Actinic keratosis
⢠Reactive atypia versus dysplasia⢠Lacks dermal mucin, follicular plugging, deep
inflammation
⢠Differential diagnosisâ Dermatomyositisâ Lichen planusâ Actinic keratosis
⢠Reactive atypia versus dysplasia⢠Lacks dermal mucin, follicular plugging, deep
inflammation
Dermatomyositis⢠Clinical
â Systemic disease withmuscle weakness(some patients haveonly cutaneousdisease)
â Heliotrope periorbitaldiscoloration
â Violaceous rash onface and neck
â Periungual erythemaâ Gottronâs papules on
hands
⢠Clinicalâ Systemic disease with
muscle weakness(some patients haveonly cutaneousdisease)
â Heliotrope periorbitaldiscoloration
â Violaceous rash onface and neck
â Periungual erythemaâ Gottronâs papules on
hands
Dermatomyositis
⢠Microscopicâ Basal vacuolizationâ Superficial perivascular mononuclear cell
infiltrate, usually mildâ Increased dermal mucin
⢠Differential diagnosisâ Lupus erythematosus
⢠Microscopicâ Basal vacuolizationâ Superficial perivascular mononuclear cell
infiltrate, usually mildâ Increased dermal mucin
⢠Differential diagnosisâ Lupus erythematosus
Practical Tips LE/DM⢠Eosinophils absent⢠Mucin helpful but non-specific⢠LE may have superficial or superficial and deep
perivascular patterns⢠âAKâ clue: reactive atypia in keratinocytes⢠DM generally does not have deep infiltrate⢠DM cannot be distinguished from LE⢠Descriptive Dx: interface dermatitis
â Note: The ddx would include connective tissuedisease such as lupus erythematosus.
⢠Eosinophils absent⢠Mucin helpful but non-specific⢠LE may have superficial or superficial and deep
perivascular patterns⢠âAKâ clue: reactive atypia in keratinocytes⢠DM generally does not have deep infiltrate⢠DM cannot be distinguished from LE⢠Descriptive Dx: interface dermatitis
â Note: The ddx would include connective tissuedisease such as lupus erythematosus.
Graft vs. Host Disease⢠Clinical
â Acute GVHD⢠Usually 2-4 weeks after bone marrow transplant⢠Late onset with lymphocyte reinfusion⢠Rarely solid organ transplants⢠Macular erythema on trunk, neck, hands, and feet⢠May form blisters⢠Systemic symptoms (e.g. diarrhea)
â Chronic GVHD⢠Months to years after bone marrow transplant⢠Lichenoid: violaceous papules on extremities, palms, and
soles⢠Sclerodermoid: presents as dermal sclerosis
⢠Clinicalâ Acute GVHD
⢠Usually 2-4 weeks after bone marrow transplant⢠Late onset with lymphocyte reinfusion⢠Rarely solid organ transplants⢠Macular erythema on trunk, neck, hands, and feet⢠May form blisters⢠Systemic symptoms (e.g. diarrhea)
â Chronic GVHD⢠Months to years after bone marrow transplant⢠Lichenoid: violaceous papules on extremities, palms, and
soles⢠Sclerodermoid: presents as dermal sclerosis
Graft vs. Host Disease⢠Microscopic
â Acute GVHD⢠Grade 0 : normal epidermis⢠Grade 1: Basal vacuolization, mild superficial
perivascular lymphocytic infiltrate⢠Grade 2: Same as Grade 1 changes with
dyskeratotic keratinocytes, satellite cell necrosis⢠Grade 3: Same as grade 2 but with cleft formation
between dermis and epidermis⢠Grade 4: Same as Grade 3 but with complete
separation of epidermis from dermis
⢠Microscopicâ Acute GVHD
⢠Grade 0 : normal epidermis⢠Grade 1: Basal vacuolization, mild superficial
perivascular lymphocytic infiltrate⢠Grade 2: Same as Grade 1 changes with
dyskeratotic keratinocytes, satellite cell necrosis⢠Grade 3: Same as grade 2 but with cleft formation
between dermis and epidermis⢠Grade 4: Same as Grade 3 but with complete
separation of epidermis from dermis
Acute GVHD, grade II
Acute GVHD grade III
Lichenoid chronic GVHD
Sclerodermoid chronic GVHD
Practical Tips: Acute GVHD
⢠Rare to see GVHD earlier than 14 days⢠May see late onset acute GVHD in some
settings⢠Eosinophils may be seen in GVHD⢠Dx of drug eruption should be approached
with caution⢠Multiple levels may be needed
⢠Rare to see GVHD earlier than 14 days⢠May see late onset acute GVHD in some
settings⢠Eosinophils may be seen in GVHD⢠Dx of drug eruption should be approached
with caution⢠Multiple levels may be needed
Dermal HypersensitivityReaction
⢠Clinical: Variableâ Drug eruptionâ Urticariaâ Arthropod bite reaction
⢠Microscopicâ Superficial or superficial and deep
perivascular infiltrateâ Lymphocytes and some eosinophils, variable
neutrophils
⢠Clinical: Variableâ Drug eruptionâ Urticariaâ Arthropod bite reaction
⢠Microscopicâ Superficial or superficial and deep
perivascular infiltrateâ Lymphocytes and some eosinophils, variable
neutrophils
Morbilliform drugeruption
⢠Clinicalâ Blanchable, Symmetric,
widespread macular orpapular eruption
⢠Microscopicâ Superficial perivascular
infiltrate of lymphocytesand eosinophils
â Mild vacuolar interfacechange sometimespresent
⢠Clinicalâ Blanchable, Symmetric,
widespread macular orpapular eruption
⢠Microscopicâ Superficial perivascular
infiltrate of lymphocytesand eosinophils
â Mild vacuolar interfacechange sometimespresent
Urticaria⢠Clinical
â Transient edematous pruritic plaques (hives)â Typically resolve in 24 hours
⢠Microscopicâ Normal epidermisâ Dermal edemaâ Superficial perivascular infiltrate of lymphocytes and
eosinophils and sometimes a few neutrophilsâ Sometimes a deeper component present
⢠Clinicalâ Transient edematous pruritic plaques (hives)â Typically resolve in 24 hours
⢠Microscopicâ Normal epidermisâ Dermal edemaâ Superficial perivascular infiltrate of lymphocytes and
eosinophils and sometimes a few neutrophilsâ Sometimes a deeper component present
Arthropod bite reaction⢠Clinical
â Solitary or groupedpapules
⢠Microscopicâ Superficial and deep
infiltrateâ Usually dense infiltrateâ Lymphocytes and
eosinophils
⢠Clinicalâ Solitary or grouped
papules⢠Microscopic
â Superficial and deepinfiltrate
â Usually dense infiltrateâ Lymphocytes and
eosinophils
Dermal hypersensitivity reaction⢠Practical Tips:
â Descriptive dx: Dermal hypersensitivity reaction, seenote
â Note: The histologic features are consistent with adermal hypersensitivity reaction such as a drugeruption. Clinicopathologic correlation isrecommended.
â Urticaria and drug eruption histologicallyindistinguishable but clinically different
â If infiltrate is dense, consider arthropod bite reaction
⢠Practical Tips:â Descriptive dx: Dermal hypersensitivity reaction, see
noteâ Note: The histologic features are consistent with a
dermal hypersensitivity reaction such as a drugeruption. Clinicopathologic correlation isrecommended.
â Urticaria and drug eruption histologicallyindistinguishable but clinically different
â If infiltrate is dense, consider arthropod bite reaction
Granuloma Annulare⢠Clinical
â Asymptomatic papuleswith annularconfiguration
â Usually on extremities
⢠Clinicalâ Asymptomatic papules
with annularconfiguration
â Usually on extremities
Granuloma Annulare⢠Microscopic
â Most commonly involves upper and mid reticulardermis
â Central zone of altered collagen fibers withassociated dermal mucin surrounded by a palisade ofhistiocytes with some giant cells
â Interstitial pattern commonâ Perivascular lymphocytic infiltrate with variable
numbers of eosinophilsâ Neutrophils may be prominent earlyâ Rarely may resemble sarcoidal granulomasâ Rarely may be confined to the subcutis
⢠Microscopicâ Most commonly involves upper and mid reticular
dermisâ Central zone of altered collagen fibers with
associated dermal mucin surrounded by a palisade ofhistiocytes with some giant cells
â Interstitial pattern commonâ Perivascular lymphocytic infiltrate with variable
numbers of eosinophilsâ Neutrophils may be prominent earlyâ Rarely may resemble sarcoidal granulomasâ Rarely may be confined to the subcutis
Granuloma Annulare
⢠Differential Diagnosisâ Necrobiosis lipoidicaâ Rheumatoid noduleâ Granulomatous drug reactionâ Sarcoidosisâ Dermatofibroma
⢠Differential Diagnosisâ Necrobiosis lipoidicaâ Rheumatoid noduleâ Granulomatous drug reactionâ Sarcoidosisâ Dermatofibroma
Practical Tips: Granuloma Annulare
⢠Palisade not always well developed⢠Low power examination⢠Altered collagen looks more âredâ⢠Interstitial pattern common
⢠Palisade not always well developed⢠Low power examination⢠Altered collagen looks more âredâ⢠Interstitial pattern common
Necrobiosis Lipoidica⢠Clinical
â Yellow, indurated plaques on lower legsâ Two-thirds of patients have underlying diabetes
mellitus⢠Microscopic
â Affects entire dermisâ Tiered arrangement of elongated zones of altered
collagen (necrobiosis) separated by an interstitialinfiltrate of histiocytes
â Multinucleated histiocytes commonâ Aggregates of lymphocytes and plasma cells
⢠Clinicalâ Yellow, indurated plaques on lower legsâ Two-thirds of patients have underlying diabetes
mellitus⢠Microscopic
â Affects entire dermisâ Tiered arrangement of elongated zones of altered
collagen (necrobiosis) separated by an interstitialinfiltrate of histiocytes
â Multinucleated histiocytes commonâ Aggregates of lymphocytes and plasma cells
Practical Tips⢠Low power examination⢠Tiers of altered collagen and histiocytes
create layer cake or bacon look⢠Plasma cells favor necrobiosis lipoidica
over GA⢠Most cases on legs⢠Ambiguous cases
⢠Dx: palisading granulomatous dermatitis⢠Note: what you favor
⢠Low power examination⢠Tiers of altered collagen and histiocytes
create layer cake or bacon look⢠Plasma cells favor necrobiosis lipoidica
over GA⢠Most cases on legs⢠Ambiguous cases
⢠Dx: palisading granulomatous dermatitis⢠Note: what you favor
RheumatoidNodule
Rheumatoid Nodule⢠Microscopic
â Lesions are located in the deep dermis,subcutaneous fat or soft tissue
â Central areas of acellular fibrin surroundedby histiocytes and giant cells in a palisadedpattern
â Lymphocytes, plasma cells and eosinophilsmay be present
⢠Microscopicâ Lesions are located in the deep dermis,
subcutaneous fat or soft tissueâ Central areas of acellular fibrin surrounded
by histiocytes and giant cells in a palisadedpattern
â Lymphocytes, plasma cells and eosinophilsmay be present
Erythema Nodosum⢠Most common form of panniculitis (>80%)⢠Acute onset of tender, erythematous
nodules⢠Shins most common site, often bilateral⢠Subcutaneous hypersensitivity reaction
â Idiopathicâ Associated with infection (e.g. group A β-
hemolytic streptococcus)â Drugs (e.g. sulfa drugs, oral contraceptives)
⢠Most common form of panniculitis (>80%)⢠Acute onset of tender, erythematous
nodules⢠Shins most common site, often bilateral⢠Subcutaneous hypersensitivity reaction
â Idiopathicâ Associated with infection (e.g. group A β-
hemolytic streptococcus)â Drugs (e.g. sulfa drugs, oral contraceptives)
Erythema Nodosum
⢠Microscopicâ Widened septae with edema, inflammation,
and later fibrosisâ Lymphocytes, histiocytes, eosinophils and
some neutrophilsâ Small granulomasâ Lobular inflammation at periphery of
subcutaneous fat lobule
⢠Microscopicâ Widened septae with edema, inflammation,
and later fibrosisâ Lymphocytes, histiocytes, eosinophils and
some neutrophilsâ Small granulomasâ Lobular inflammation at periphery of
subcutaneous fat lobule
Erythema Nodosum
⢠Differential Diagnosisâ Infectionâ Traumaâ Erythema induratumâ Lipodermatosclerosis
⢠Differential Diagnosisâ Infectionâ Traumaâ Erythema induratumâ Lipodermatosclerosis
Nodular Vasculitis(Erythema Induratum)
⢠Clinicalâ Chronic, recurring tender nodules on lower legs,
especially calvesâ Subcutaneous hypersensitivity
⢠Subset: reaction to underlying infection with M. tuberculosis
⢠Microscopicâ Acute vasculitis in septae affecting artery and/or veinsâ Adjacent lobular panniculitis with granulomas and fat
necrosisâ Septae may be widened in older lesions
⢠Clinicalâ Chronic, recurring tender nodules on lower legs,
especially calvesâ Subcutaneous hypersensitivity
⢠Subset: reaction to underlying infection with M. tuberculosis
⢠Microscopicâ Acute vasculitis in septae affecting artery and/or veinsâ Adjacent lobular panniculitis with granulomas and fat
necrosisâ Septae may be widened in older lesions
Lipodermatosclerosis⢠Clinical
â Usually bilateralindurated plaques onmedial aspects oflower legs
â Associated with stasischanges secondary tovenous insufficiencyand obesity
⢠Clinicalâ Usually bilateral
indurated plaques onmedial aspects oflower legs
â Associated with stasischanges secondary tovenous insufficiencyand obesity
Lipodermatosclerosis
⢠Microscopicâ Widened septaeâ Membranocystic fat necrosis
⢠Cystic cavities lined by a crenulated, hyaline membraneâ Mild perivascular lymphocytic infiltrateâ Overlying features of stasis change in dermis and
epidermis
Panniculitis practical tips
⢠Look for predominant pattern at low power⢠Most cases are erythema nodosum⢠Absence of inflammation: think
lipodermatosclerosis
⢠Look for predominant pattern at low power⢠Most cases are erythema nodosum⢠Absence of inflammation: think
lipodermatosclerosis
Bonus Diagnosis:Chondrodermatitis Nodularis
Helicis
Bonus Diagnosis:Chondrodermatitis Nodularis
Helicis
Chondrodermatitis NodularisHelicis (CNCH)
⢠Clinicalâ Older patientsâ Crusted to ulcerated lesion on helixâ On âsleeping sideââ Essentially a small pressure ulcerâ Clinically mimics squamous cell carcinoma or
basal cell carcinoma
⢠Clinicalâ Older patientsâ Crusted to ulcerated lesion on helixâ On âsleeping sideââ Essentially a small pressure ulcerâ Clinically mimics squamous cell carcinoma or
basal cell carcinoma
CNCH
⢠Microscopicâ Ulcerâ Reactive epidermal hyperplasiaâ Fibrinoid degeneration of dermisâ Proliferation of perichondrial fibroblasts
⢠Microscopicâ Ulcerâ Reactive epidermal hyperplasiaâ Fibrinoid degeneration of dermisâ Proliferation of perichondrial fibroblasts
CNCH
⢠Tipsâ High index of suspicion from ear lesionsâ Fibrinoid changeâ Absence of atypia
⢠Tipsâ High index of suspicion from ear lesionsâ Fibrinoid changeâ Absence of atypia
Bonus Diagnosis: Rosacea⢠Clinical features
â Predominantly involves central faceâ Erythema, telangiectasia earlyâ Acneiform lesions, pustules, papules laterâ Can mimic basal cell carcinoma
⢠Microscopic featuresâ Perivascular and perifollicular infiltrateâ Lymphocytes, histiocytes, sometimes
granulomas
⢠Clinical featuresâ Predominantly involves central faceâ Erythema, telangiectasia earlyâ Acneiform lesions, pustules, papules laterâ Can mimic basal cell carcinoma
⢠Microscopic featuresâ Perivascular and perifollicular infiltrateâ Lymphocytes, histiocytes, sometimes
granulomas
Rosacea Practical Tips
⢠If BCC suspected clinically, get deeperlevels
⢠Diagnosis: Perivascular and perifollicularlymphohistiocytic infiltrate, see comment
⢠Comment: The histologic features areconsistent with rosacea in the right clinicalcontext. CPC recommended.
⢠If BCC suspected clinically, get deeperlevels
⢠Diagnosis: Perivascular and perifollicularlymphohistiocytic infiltrate, see comment
⢠Comment: The histologic features areconsistent with rosacea in the right clinicalcontext. CPC recommended.