Clinical correlation ofClinical correlation of
inflammatory skininflammatory skin
lesionslesions
Mary Jo Robinson, D.O.Mar...
5 clinical keys to diagnosis5 clinical keys to diagnosis
• Type of lesions-very very important
• Region of body affected- ...
8 clinical diagnostic groups8 clinical diagnostic groups
• Pustular-pustule
• Vesicular bullous-vesicles or bullae
• Papul...
>2000 clinical dermatologic diseases>2000 clinical dermatologic diseases
• Many with variety of presentations and
tendency...
100 most common dermatologic dzs100 most common dermatologic dzs
• Represent 85% of problems seen by
practicing dermatolog...
So how does the pathologistSo how does the pathologist
correlate these clinical impressionscorrelate these clinical impres...
PustularPustular
• Microscopic
• Collections of
neutrophils,
eosinophils or
lymphocytes in
epidermis, follicle,
sebaceous ...
Generalized and intenseGeneralized and intense
erythematous rash with pustuleserythematous rash with pustules
Palmoplantar pustulesPalmoplantar pustules
MacropustuleMacropustule
PustularPustular
psoriasispsoriasis
• Biopsy to exclude
fungus, pustular
drug, impetigo,
superficial
pemphigus,
impetigo
h...
Histology not specific, CCHistology not specific, CC
necessarynecessary
• Pustular psoriasis cannot be
distinguished on hi...
Papular minivesicularPapular minivesicular
• Microscopic
• Epidermal
spongiosis w/ scale
crust
• Macroscopic
• Papular min...
Intensely pruritic rash ofIntensely pruritic rash of
elbows, knees, backelbows, knees, back
Early
Late
Floor ofFloor of
blisterblister
DIF granular IgA in dermalDIF granular IgA in dermal
papillaepapillae
D/Dx DH via DIFD/Dx DH via DIF
• DIF DH- granular IgA
• Linear IgA dermatosis-linear IgA
also lack of gluten sensitive
ent...
Dermatitis herpetiformisDermatitis herpetiformis
• clinically Grover’s, atopic dermatitis,
scabies & Pityriasis lichenoide...
• Clinician should biopsy nonexcoriated, non-
vesicular erythematous plaque or papule for
best diagnosis
• d/dx of neutrop...
VesiculobullousVesiculobullous
• Microscopic
• Epidermal or
subepidermal
vesicle(<10mm)
• Bullae(>10 mm)
• Macroscopic
• B...
Firm bullae w/ erosions,Firm bullae w/ erosions,
crusts, papules and whealscrusts, papules and wheals
• groin, axillae,
fo...
HistopathologyHistopathology
DIF linear IgG
DIF Salt split skin IgG
Type IV collagen present alongType IV collagen present along
base of blisterbase of blister
EBA - collagen along roof of b...
Bullous pemphigoidBullous pemphigoid
• Histology- epidermal
spongiosis
• Rete ridge pattern
preserved
• Subepidermal
blist...
Histologic d/dxHistologic d/dx
• Spongiotic
arthropod assault
• Herpes gestationis
• Porphyria cutanea
tarda
• Erythema
mu...
Pruritic vesiculopustular diseasePruritic vesiculopustular disease
of trunk and proximal extremitiesof trunk and proximal ...
HistologyHistology
• Subcorneal pustules
to bullae with
neutrophilic
infiltrate w/ sparse
to moderate
numbers of
eosinophi...
IgA pemphigusIgA pemphigus
• Presented case is
SPD type
(subcorneal
pustular
dermatosis)
• Resemble
SPD/Sneddon-
Wilkinson...
IEN typeIEN type
Intraepidermal
pustules of
neutrophils
and some
eosinophils
IgA DIFIgA DIF
• Intercellular IgA deposits
• SPD form shows antibodies to
desmocollin-1
• Some cases of IEN form antibodi...
PapulosquamousPapulosquamous
• Microscopic
• Confluent
orthokeratosis,
parakeratosis or
alternating OK/PK
sometimes with
m...
ClinicalClinical
• Scaly
• Large scale(flakes)
> 1mm size=
large scale dz
(psoriasiform)
• Small scales
< 1 mm size=
small...
HistopathologyHistopathology
• Large scale usually
psoriasiform
may be
spongiotic, interface
vacuolar or interface
• Small...
Plaques with overlying scalePlaques with overlying scale
and erythematous bordersand erythematous borders
IgG, complement
band at base of
epidermis on IF
Lupus erythematosusLupus erythematosus
• Annular to plaques
• Photosensitive distribution
• Scales
• Atrophy/scarring(late...
Follicular pluggingFollicular plugging
Polymorphous autoimmunePolymorphous autoimmune
diseasedisease
• primary changes at epidermal dermal
interface including ha...
Stage of disease affectsStage of disease affects
histologyhistology
• Early – maculopapular more superficial
sparse inflam...
Histologic D/DXHistologic D/DX
• Seborrheic dermatitis- early forms w/
pyknotic neutrophils @ follicular ostia, later
chro...
Flat topped violaceousFlat topped violaceous
papules w/ shiny scalepapules w/ shiny scale
HistologyHistology
Lichen planusLichen planus
• Compact orthokeratosis
• If rubbed, parakeratosis &/or
hypertrophic
• Acanthosis with jagged ...
Dermis in LPDermis in LP
• lichenoid lymphohistiocytic infiltrate
fills papillary dermis, is dense and
close to base of ep...
D/Dx of lichenoid lesionsD/Dx of lichenoid lesions
• Lichenoid photodermatitis-sup & deep w/
spongiosis
• Lichenoid solar ...
PapulonodularPapulonodular
• Microscopic
• Scale crust and
spongiosis are
ABSENT
• Acanthosis, dermal
deposits or
inflamma...
Grouped 1-2 mm flesh colored toGrouped 1-2 mm flesh colored to
pink papules in arcuatepink papules in arcuate
distribution...
Clinical d/dxClinical d/dx
• Sarcoid
• Lichen planus
• Urticaria pigmentosa
• Papular mucinosis
• Tinea corporis
• Necrobi...
Granuloma annulare HistologyGranuloma annulare Histology
D/Dx palisading granulomaD/Dx palisading granuloma
• Granuloma annulare
• Rheumatoid nodules
• Necrobiosis
lipoidica
• Chu...
Vascular dominantVascular dominant
• Microscopic
• Proliferations of
blood vessels
• Or perivascular
inflammatory
infiltra...
Purpura as a clinical cluePurpura as a clinical clue
• Non-purpuric
complete
blanching with
application of
pressure, no
ex...
Bright red to brown red purpuricBright red to brown red purpuric
papules lower extremitiespapules lower extremities
HistologyHistology
Endothelial cell swelling, angiocentric
neutrophilic inflammation with nuclear dust,
fibrin in vessel w...
Henoch-Schoenlein purpura-IgAHenoch-Schoenlein purpura-IgA
mediated in kids(beta strept)mediated in kids(beta strept)
PigmentaryPigmentary
• Microscopic
• Pigment containing
macrophages in
upper dermis
• decreased or
increased number of
mel...
White to yellow linear plaquesWhite to yellow linear plaques
with violaceus to erythematouswith violaceus to erythematous
...
Histology linear morpheaHistology linear morphea
TumorTumor
• Microscopic
• neoplastic
proliferation of cells
• epidermal
• Dermal
• Melanocytic
• other
• Macroscopic
• My...
15 top inflammatory skin lesions15 top inflammatory skin lesions
submitted to pathologysubmitted to pathology
• Arthropod ...
ReferencesReferences
• Bolognia, Jorizzo & Rapini,
Dermatology, 2003:Elsevier,
www.dermtext.com
• McKee, et.al. ,Pathology...
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  • Gok=god only knows
  • DIF DH- granular IGA; Linear IgA dermatosis-linear IgA, lack of gluten sensitive enteropathy, Bullous pemphigoid-linear IgG
  • Linear IgG which on salt split skin binds to roof of blister
  • Bx usually done for medico/legal reasons prior to tx w/ steroids, to exclude LE and lichenoid drug
  • -Clinical correlation of ...

    1. 1. Clinical correlation ofClinical correlation of inflammatory skininflammatory skin lesionslesions Mary Jo Robinson, D.O.Mary Jo Robinson, D.O. UMDNJ-SOMUMDNJ-SOM Oct.3, 2007Oct.3, 2007
    2. 2. 5 clinical keys to diagnosis5 clinical keys to diagnosis • Type of lesions-very very important • Region of body affected- also important • Distribution of lesions-not that important • Color-somewhat important • Configuration/shape-less important • Summary- pertinent history and complete skin examination is best key.
    3. 3. 8 clinical diagnostic groups8 clinical diagnostic groups • Pustular-pustule • Vesicular bullous-vesicles or bullae • Papular mini-vesicular- vesicles less than 2 mm • Papulosquamous-scales • Papulonodular-non red nodule, no scale or crust • Vascular dominant-red macule, papule or nodule w/o epidermal changes • Pigmentary-brown, black, white or yellow lesions • Tumor –large papules or nodules
    4. 4. >2000 clinical dermatologic diseases>2000 clinical dermatologic diseases • Many with variety of presentations and tendency to change during the chronology of disorder • Thus one disease can have a myriad of radically different presentations, ie. Lupus
    5. 5. 100 most common dermatologic dzs100 most common dermatologic dzs • Represent 85% of problems seen by practicing dermatologist • But most do not need bx-acne, rosacea, seborrheic dermatitis , psoriasis, tinea corporis….diagnosed clinically w/o bx • But atypical presentations of above and a subgroup of patients called “GOK” tend to get biopsies
    6. 6. So how does the pathologistSo how does the pathologist correlate these clinical impressionscorrelate these clinical impressions?? • Given the clinical impression (macroscopic)try to subclassify into microscopic appearance • Such as clinician describes scales, slide shows alternating parakeratosis and orthokeratosis= PRP • Clinician describes pustules, slide shows collections of neutrophils in stratum corneum= pustular psoriasis
    7. 7. PustularPustular • Microscopic • Collections of neutrophils, eosinophils or lymphocytes in epidermis, follicle, sebaceous glands, etc • Macroscopic • Pustular dermatosis - impetigo - folliculitis - acne - Rosacea - candidiasis - Pustular psoriasis - Sweet’s
    8. 8. Generalized and intenseGeneralized and intense erythematous rash with pustuleserythematous rash with pustules
    9. 9. Palmoplantar pustulesPalmoplantar pustules
    10. 10. MacropustuleMacropustule
    11. 11. PustularPustular psoriasispsoriasis • Biopsy to exclude fungus, pustular drug, impetigo, superficial pemphigus, impetigo herpetiformis • Should culture
    12. 12. Histology not specific, CCHistology not specific, CC necessarynecessary • Pustular psoriasis cannot be distinguished on histology from - acrodermatitis continua(pustular eruption on one of more fingers) - Reiter’s disease(arthritis, conjunctivitis, balanitis, pustular dermatosis) - impetigo herpetiformis( pustular dermatosis of pregnancy assoc w/ hypocalcemia)
    13. 13. Papular minivesicularPapular minivesicular • Microscopic • Epidermal spongiosis w/ scale crust • Macroscopic • Papular minivesicular dermatitis - contact dermatitis - atopic dermatitis - scabies - dermatophytosis - stasis dermatitis - Grover’s - Hailey Hailey - Mucha-Habermann - Dermatitis herpetiformis
    14. 14. Intensely pruritic rash ofIntensely pruritic rash of elbows, knees, backelbows, knees, back
    15. 15. Early Late
    16. 16. Floor ofFloor of blisterblister
    17. 17. DIF granular IgA in dermalDIF granular IgA in dermal papillaepapillae
    18. 18. D/Dx DH via DIFD/Dx DH via DIF • DIF DH- granular IgA • Linear IgA dermatosis-linear IgA also lack of gluten sensitive enteropathy, no association w/HLA-B8 &DR-3 antigens, less response to dapsone tx • Bullous pemphigoid-linear IgG
    19. 19. Dermatitis herpetiformisDermatitis herpetiformis • clinically Grover’s, atopic dermatitis, scabies & Pityriasis lichenoides are always part of differential. • Commonly due to intense pruritus of DH, a bx will come in as r/o scabies or atopic dermatitis • Biopsy may often show only erosions or scale crusts
    20. 20. • Clinician should biopsy nonexcoriated, non- vesicular erythematous plaque or papule for best diagnosis • d/dx of neutrophils in papillary dermis includes Bullous eruption of LE, mucous membrane pemphigoid, flea bites, leukocytoclastic vasculitis, linear IgA dermatosis. • Clinical response to dapsone can be used as confirmatory test • 2/3 pts have asymptomatic celiac –like disease on jejunal bx & endomysial antibodies
    21. 21. VesiculobullousVesiculobullous • Microscopic • Epidermal or subepidermal vesicle(<10mm) • Bullae(>10 mm) • Macroscopic • Burn • Erythema multiforme • Pemphigus vulgaris • Dermatitis herpetiformis • Herpes simplex • Bullous pemphigoid • Contact dermatitis • Fixed drug eruptions
    22. 22. Firm bullae w/ erosions,Firm bullae w/ erosions, crusts, papules and whealscrusts, papules and wheals • groin, axillae, forearms, oral • Intertriginous to generalized • Pink to red
    23. 23. HistopathologyHistopathology
    24. 24. DIF linear IgG DIF Salt split skin IgG
    25. 25. Type IV collagen present alongType IV collagen present along base of blisterbase of blister EBA - collagen along roof of blister
    26. 26. Bullous pemphigoidBullous pemphigoid • Histology- epidermal spongiosis • Rete ridge pattern preserved • Subepidermal blister • Early bullae will have many eosinophils • Clinician should biopsy erythematous skin with early bullae • Perilesional skin should be biopsied for DIF
    27. 27. Histologic d/dxHistologic d/dx • Spongiotic arthropod assault • Herpes gestationis • Porphyria cutanea tarda • Erythema multiforme • Dermatitis herpetiformis • Linear IgA bullous dermatosis • Epidermolysis bullosa • Bullous lichen planus • Bullous drug eruption • Bullous LE
    28. 28. Pruritic vesiculopustular diseasePruritic vesiculopustular disease of trunk and proximal extremitiesof trunk and proximal extremities Note the vesicles start clear and then fill with white creamy pus, then erosions form
    29. 29. HistologyHistology • Subcorneal pustules to bullae with neutrophilic infiltrate w/ sparse to moderate numbers of eosinophils
    30. 30. IgA pemphigusIgA pemphigus • Presented case is SPD type (subcorneal pustular dermatosis) • Resemble SPD/Sneddon- Wilkinson, pemphigus foliaceous • Second clinical type is IEN type (interepidermal neutrophilic bullae) • Annular erythema with peripheral vesicular eruption
    31. 31. IEN typeIEN type Intraepidermal pustules of neutrophils and some eosinophils
    32. 32. IgA DIFIgA DIF • Intercellular IgA deposits • SPD form shows antibodies to desmocollin-1 • Some cases of IEN form antibodies to desmoglein1 • Both have serum antibodies to IgA epithelial cell surfaces by IFA • Differentiates from Pemphigus foliaceus which has IgG epithelial cell surface
    33. 33. PapulosquamousPapulosquamous • Microscopic • Confluent orthokeratosis, parakeratosis or alternating OK/PK sometimes with minimal serum • Macroscopic • Lichen planus • Psoriasis • Lupus erythematosus • Pityriasis rosea • Seborrheic dermatitis • Solar keratosis • Scaly dermatophytosis • Ichthyosis • Mycosis fungoides • Pityriasis rubra pilaris
    34. 34. ClinicalClinical • Scaly • Large scale(flakes) > 1mm size= large scale dz (psoriasiform) • Small scales < 1 mm size= small scale dz (pityriasis) • Shiny compact scales compact scale dz (lichenoid)
    35. 35. HistopathologyHistopathology • Large scale usually psoriasiform may be spongiotic, interface vacuolar or interface • Small scale usually spongiotic, but may be interface vacuolar or interface • Compact scale usually interface but spongiotic or interface vacuolar may be seen
    36. 36. Plaques with overlying scalePlaques with overlying scale and erythematous bordersand erythematous borders
    37. 37. IgG, complement band at base of epidermis on IF
    38. 38. Lupus erythematosusLupus erythematosus • Annular to plaques • Photosensitive distribution • Scales • Atrophy/scarring(late) • Follicular plugging(late) • Dermal edema &/or mucin deposits • Telangiectases • Lichenoid to sup & deep pv lymph infiltrate
    39. 39. Follicular pluggingFollicular plugging
    40. 40. Polymorphous autoimmunePolymorphous autoimmune diseasedisease • primary changes at epidermal dermal interface including hair follicle • Vacuolar change • BM thickening –chronic cases PAS • Compact Orthokeratosis • Loss of rete ridges late • Necrotic keratinocytes occasionally
    41. 41. Stage of disease affectsStage of disease affects histologyhistology • Early – maculopapular more superficial sparse inflammation, lichenoid and may be neutrophilic • Later smudging subtle to progress to more obvious vacuolar • Then plaque stage shows dermal mucin and adnexal inflammation • Late- scarring, atrophy, melanophages
    42. 42. Histologic D/DXHistologic D/DX • Seborrheic dermatitis- early forms w/ pyknotic neutrophils @ follicular ostia, later chronic forms more spongiosis • Actinic keratosis- interface changes due to solar damage, check the follicular ostia, no interface change there? It is not DLE • Lichen planus • PMLE- no atrophy, no foll. plugging, no fibrosis • Rosacea –central face especially, but more vascular than LE & assoc clinically w/ flushing, perifollicular infl, no mucin
    43. 43. Flat topped violaceousFlat topped violaceous papules w/ shiny scalepapules w/ shiny scale
    44. 44. HistologyHistology
    45. 45. Lichen planusLichen planus • Compact orthokeratosis • If rubbed, parakeratosis &/or hypertrophic • Acanthosis with jagged sawtoothed rete ridges • Focal wedge-shaped hypergranulosis that is more prominent next to acrosyringium • Colloid bodies- more prominent in lower epidermis
    46. 46. Dermis in LPDermis in LP • lichenoid lymphohistiocytic infiltrate fills papillary dermis, is dense and close to base of epidermis • Coarse collagen bundles • No mucin, no edema
    47. 47. D/Dx of lichenoid lesionsD/Dx of lichenoid lesions • Lichenoid photodermatitis-sup & deep w/ spongiosis • Lichenoid solar keratosis-atypical budding w/ alternating ok/pk • Lichenoid LE-vacuolar change prominent, dermal mucin, may be tough call • Lichen aureus-pigmented purpuric dermatosis, hemosiderin macrophages • MF- epidermotropism, lamellar fibrosis • LPLK- usually solitary, peripheral SK/SL
    48. 48. PapulonodularPapulonodular • Microscopic • Scale crust and spongiosis are ABSENT • Acanthosis, dermal deposits or inflammation are PRESENT • Macroscopic • Prurigo nodularis • Granuloma annulare • Amyloidosis • Sarcoid • Acne • Follicular cysts • Arthropod assaults • Lymphocytoma cutis • Polyarteritis nodosa
    49. 49. Grouped 1-2 mm flesh colored toGrouped 1-2 mm flesh colored to pink papules in arcuatepink papules in arcuate distribution on extremitiesdistribution on extremities
    50. 50. Clinical d/dxClinical d/dx • Sarcoid • Lichen planus • Urticaria pigmentosa • Papular mucinosis • Tinea corporis • Necrobiosis lipoidica • Rheumatoid nodule • Foreign body • Granulomatous rosacea
    51. 51. Granuloma annulare HistologyGranuloma annulare Histology
    52. 52. D/Dx palisading granulomaD/Dx palisading granuloma • Granuloma annulare • Rheumatoid nodules • Necrobiosis lipoidica • Churg-Strauss granulomatosis • Lupus miliaris disseminatus facei • Bovine collagen injections • Actinic granuloma • Foreign body granuloma • Infectious granuloma
    53. 53. Vascular dominantVascular dominant • Microscopic • Proliferations of blood vessels • Or perivascular inflammatory infiltrate w/ no epidermal changes • Redness, macular or papular erythema • Wheals • purpura • Macroscopic • Urticarial vasculitis • Macular papular erythema • Vasculitis • Gyrate erythema • Schamberg’s • telangiectasia Hemangiomas • Kaposi’s
    54. 54. Purpura as a clinical cluePurpura as a clinical clue • Non-purpuric complete blanching with application of pressure, no extravasated rbc’s in dermis • Sunburn, urticaria, macular papular erythema, erythema nodosum, fixed drug, gyrate erythemas • Purpuric residual erythema persists with pressure ecchymosis and petechiae • Leukocytoclastic vasculitis, septic vasculitis, pigmented purpura, dysproteinemic purpura, thrombocytopenic purpura
    55. 55. Bright red to brown red purpuricBright red to brown red purpuric papules lower extremitiespapules lower extremities
    56. 56. HistologyHistology Endothelial cell swelling, angiocentric neutrophilic inflammation with nuclear dust, fibrin in vessel walls, extravasated erythrocytes
    57. 57. Henoch-Schoenlein purpura-IgAHenoch-Schoenlein purpura-IgA mediated in kids(beta strept)mediated in kids(beta strept)
    58. 58. PigmentaryPigmentary • Microscopic • Pigment containing macrophages in upper dermis • decreased or increased number of melanocytes in epidermis • Of dermis with collections of histiocytic foams cells in dermis fibrosis • Macroscopic • Lichen sclerosus • Vitiligo • Lentigo • Xanthelasma • Lupus erythematosus • Morphea • Tinea versicolor • Melanocytic nevus • Basal cell carcinoma, pigmented • Seborrheic keratosis • Dermatofibroma
    59. 59. White to yellow linear plaquesWhite to yellow linear plaques with violaceus to erythematouswith violaceus to erythematous halohalo
    60. 60. Histology linear morpheaHistology linear morphea
    61. 61. TumorTumor • Microscopic • neoplastic proliferation of cells • epidermal • Dermal • Melanocytic • other • Macroscopic • Mycosis fungoides • Kaposi sarcoma • Melanoma • Basal cell carcinoma • Seborrheic keratosis • Sebaceous hyperplasia • Etc.
    62. 62. 15 top inflammatory skin lesions15 top inflammatory skin lesions submitted to pathologysubmitted to pathology • Arthropod assault • Erythema multiforme • Fixed drug • Granuloma annulare • Jessner’s/ lymphocytoma cutis • Lesion • Lichen planus • Leukocytoclasitc vasculitis • Mycosis fungoides/ parapsoriasis • Polymorphous light eruption • Psoriasis • Scleroderma/morphea • Urticaria • vasculitis
    63. 63. ReferencesReferences • Bolognia, Jorizzo & Rapini, Dermatology, 2003:Elsevier, www.dermtext.com • McKee, et.al. ,Pathology of the Skin with Clinical Correlations, 3rd ed. 2005:Elsevier. • Bozzo P & Miller RC Clinical Dermatology and Dermatopathology: A Dynamic Interface series of ASCP lectures.

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