Transcript subepidermal bulla

Insitu malignant melanoma
Pagetoid
spread
of malignant
melanocytes
(arrows)
confined to
the epidermis
Lymphocytes in
dermis
Invasive Malignant melanoma
Mitoses –prognostic factor 3
pigmented
non pigmented
Melanoma cells are large with round nuclei containing nucleolus
Mitoses (arrow)
Ulcerated nodular melanoma
Ulceration -prognostic factor 4
Ulceration
Sentinel Node Biopsy
•
Performed in patients with
- invasive melanoma of ≥1mm Breslow
thickness or Clark level IV
- no clinically evident metastatic disease
•
+Sentinel node is the most important
prognostic factor in invasive melanoma
≥1mm Breslow thickness
Sentinel node: metastatic melanoma
Prognostic factor 5
Lymph node
Melanoma
Melanoma- 6 Major
Prognostic Factors in TNM
staging
Breslow thickness
• Clark level
• Mitoses
• Ulceration
• Sentinel lymph node status
• Satellite nodule (intransit metastasis)
•
Important slide
SKIN RASHES
Clinicopathologic Review Session
W
How to Describe a Lesion
SCALDA – Loo
Very important
Size
• Color
• Arrangement (configuration)
• Lesion morphology
• Distribution
• Always check hair, nail, mucosa,
intertriginous areas
•
Arrangement (configuration) - manner in which
lesions relate to one another
Grouped
Annular
Linear
SCALDA
Geographic
Lesional morphology
Macule/patch: ≤/>1cm flat lesion
• Papule/plaque: ≤/> 1cm raised lesion
• Nodule: >1 cm raised lesion, rounded
surface
• Vesicle/bulla: ≤/> 1 cm blister
• Surface - scale/crust/excoriated
– Scale: dry/flaky surface
- Crust (Scab): wet, dried serum, pus
or blood
- Excoriation: scratching
•
SCALDA
Rashes for Clinicians
Dermatitis (Eczema)
• Papulosquamous lesions
• Vasculitis, cutaneous manifestations of
systemic diseases
• Drug reactions
• Vesiculo-bullous diseases
• Infections
• Acne
•
Rashes - Role of a pathologist
3-5% of lesions -difficult for clinicians
-G od
-O nly
-K nows
• Biopsy -Single Most Important Test
•
Biopsy Methods
Excisional B
Tumor
Rash
Incisional B
Punch B
Shave B
Punch
biopsy
3mm
4mm
6mm
Selection of Punch BiopsySelection
of
Biopsy
Rash
Biopsy early/well developed rashes
• Avoid
•
- excoriated lesions, ulcers
- Burned out late lesions
- Sec. infected lesions
Biopsy periphery of lesion
including normal skin
•
Biopsy transportation
BiopsyF ixatives
Universal fixative in Pathology is 10%
neutral buffered formalin
• For immunofluorescence testing Michel’s transporting medium
•
Skin: Histology
Epidermis and Dermis
Stratum Corneum
• Stratum
Granulosum
• Stratum Spinosum
• Stratum Basalis
•
1. DERMATITIS (eczema)
•
Non infective inflammatory
reaction of the skin affecting the
epidermis and dermis due to a
variety of causes.
Dermatitis: Common Types &
Pathogenesis
Allergic contact dermatitis - Type 1V
hypersensitivity reaction
• Irritant contact dermatitis - direct toxic
effect, non immune
• Nummular dermatitis -unknown cause
• Atopic dermatitis - children- Type 1 (IgE
mediated) hypersensitivity reaction
•
Dermatitis: Common Types &
Pathogenesis
Seborrheic dermatitis - Pityrosporum
ovale
• Stasis dermatitis - venous stasis
• Lichen Simplex Chronicus -repeated
rubbing and scratching of skin
•
A question
W
chronic from acute dermatitis
A)
B)
C)
D)
E)
Lichenification
Erythema and edema
Vesicles and blisters
Exudation
Crusting
Dermatitis – 3 phases
Pathophysiology
1) Acute dermatitis
2) Subacute dermatitis
3) Chronic dermatitis
Dermatitis – 3 phases
Pathophysiology
1) Acute dermatitis - spongiosis, microvesicles
(pain, erythema, edema, vesicles, itchy)
2) Subacute dermatitis - scaling, crusting
3) Chronic dermatitis - scaling and thickening of
skin with increased skin markings
(lichenification, related to repeated
scratching)
Important Integration slide
Acute Dermatitis
Acute allergic contact
dermatitis
Poison Ivy
Acute dermatitis
Acute atopic dermatitis
Subacute dermatitis
Subacute atopic dermatitis
Chronic dermatitis
Lichenification
Chronic dermatitis
Lichenification
Acute D
SPONGIOSIS: intercellular edema
(A), microvesicles (B), dermal
inflammation (C)
A
C
A
Normal skin
B
Chronic D
Lichenification: hyperkeratosis
(A), acanthosis (B), dermal
fibrosis (C)
A
B
C
Normal skin
Thickening of all
layers of skin
What single feature distinguishes
chronic from acute dermatitis
A)
B)
C)
D)
E)
Lichenification
Erythema and edema
Vesicles and blisters
Exudation
Crusting
Answer: A
2. PAPULOSQUAMOUS
DISEASES
A group of etiologically unrelated skin
disorders where lesions share a
common clinical appearance
-Papular, but may contain other forms,
- well demarcated
- scaly
• Psoriasis, Lichen planus and Pityriasis
rosea
•
Dermatitis vs Papulosquamous D
A
B
Psoriasis: clinical forms
Psoriasis vulgaris - most common type
• Guttate psoriasis
• Pustular psoriasis
• Erythrodermic psoriasis
• Psoriatic nails
• Psoriatic arthritis
•
Psoriasis Vulgaris vs Guttate Psoriasis
Discrete erythematous
plaques, silvery white scale
Generalized, rapid onset,
follow strep throat
multiple smaller
erythematous plaques,
scale minimal
A Psoriasis Vulgaris case
Well circumscribed
Erythematous (salmon
pink)
papules/plaques with
silvery white scale
• Kobner phenomenon:
lesions appear at site of
repeated trauma
• Auspitz’s sign -removal
of scale results in
minute bleeding points
•
Auspitz sign
Pinpoint bleeding areas where scale is removed
What is this phenomenon -Koebner P
Psoriasis Vulgaris - Pathology
Parakeratosis (silvery
scale)
Acanthosis
Dilated vessels,
dermal inflammation
Inflammation and epidermal proliferation
Study Psoriasis -under the microscope
A
B
C
For information only
Psoriasis
Pathophysiology
Increased epidermal turn over or shortened
cell cycle from 311 to 36 hours which results
in 28 times the normal production of
epidermal cells of psoriatic skin
• T cell mediated, CD4 T cells mediate
epidermal proliferation
• Stratum corneum is abnormally formed
• Cause unclear, role for genetic and
environmental factors
•
Pityriasis Rosea
Pityriasis Rosea
Common, self limiting, disease of children
• Cause is unknown, but may follow various
infections, debate regarding HHV-7 (viral)
• Herald patch -first lesion, larger
• Symmetrial smaller lesions appear within 2
weeks on trunk, thighs and arms -christmas
tree -like arrangement
• Mostly a clinical diagnosis, biopsy rarely
needed
•
Pityriasis Rosea
Herald patch
and multiple round or
oval macules with fine
scale at the periphery
of each lesion
CHRISTMAS TREE
Herald patch
Lichen Planus (5 P’s)
Purple (violaceous)
• Pruritic
• Polygonal
• Planar
• Papules
•
x
Flat topped
Lichen Planus
Acute or chronic inflammatory
dermatosis involving skin and mucous
membrane
• Idiopathic in most cases
• Possible HLA associated genetic
susceptibility
•
Lichen Planus
Location
Skin -flexural surfaces,
wrists
Mucous membrane-mouth
Nail
Hair loss
Koebner phenomenon: lesions
appear at site of trauma
Hepatitis C has been
associated
Lichen Planus -Pathology
Hyperkeratosis
(Scale)
Irregular acanthosis
Basal cell damage
Band of lymphocytes
Inflammatory injury to the basal cells of the epidermis
leads to epidermal thickening and scaling
Study Lichen Planus: under the
microscope
A
B
C
D
For information only
Prepare
Vasculitis -common types, causes
• Cutaneous manifestations of systemic
disease
•
- Diabetes
- Lupus
- Dermatomyositis
Drug reactions - common types
• All signs and phenomenon
• Acne
•
Vasculitis (inflammation of
vessel) RED RASH
Definition
• How to recognize, why
palpable
• Causes
•
- infection,
- drug
- connective tissue D
- neoplasia
- idiopathic
- blood disorder
Histology
• Approach
•
Palpable purpura, do not
blanch on pressure
B
C
A
Vasculitis histology: Red cells (A), inflammation (B),
and fibrinous necrosis of dermal vessels (C).
Palpable purpura (clinical)
BLISTERING SKIN DISEASES
or VESICULO-BULLOUS
DISEASES
Blister
Classification
Size
- Vesicle <1cm
- Bulla >1cm
Location
- Intraepidermal
- Subepidermal
VESICULO-BULLOUS
DISEASES
•
Immunobullous
- Pemphigus Vulgaris
-Bullous Pemphigoid
- Dermatitis Herpetiformis
Objective: Compare and contrast these
immunobullous diseases in terms of
clinical morphology and histology
A Pemphigus Vulgaris Case
56- year-old male of
Mediterranean decent
presented with severe
generalized flaccid
bullae, many ruptured
and turned into
erosions. Scalp, face
and chest are affected.
Oral lesions are
present. Positive
Nikolsky sign
• Skin biopsy shows
intraepidermal bulla
•
A Bullous Pemphigoid Case
80 year old female
presented with multiple
scattered large tense
firm topped bullae on
an erythematous base,
involve lower legs,
abdomen. Negative
Nikolsky sign. No oral
lesions (oral lesions in
only 10-30% of BP)
• A skin biopsy showed a
subepidermal bulla.
•
Pemphigus Vulgaris
Intraepidermal bulla,
acantholysis
(Flaccid)
Bullous Pemphigoid
Subepidermal bulla
(Tense)
Pemphigus Vulgaris vs Bullous Pemphigoid
PV: acantholysis = flaccid blisters
BP: subepidermal = tense blisters
Pemphigus Vulgaris
Pathogenesis
•
Circulating
antibodies of IGG
class, bind to
pemphigus antigens
(desmoglein 3) of
epidermal
desmosome, induce
acantholysis and
intraepidermal
bullae.
The molecular structure of the desmosome
Desmoplakin 2 (215 kd)
Plaque Plakoglobin
(85 kd)
Plakophilin 1,2,3 (75 kd)
Keratocalmin (250 kd)
Desmoglein 1 (165 kd)
Desmoglein 2 (Colon)
Core Desmoglein 3 (130 kd)
Desmocollins:
1a, b
2a, b
3a, b
Other Plaque Components: Envoplakin, Perlplakin, and
Corneodesmosin (Keratinocyte Envelops)
Pemphigus Vulgaris
Immunopathology
•
Direct
immunofluoresence
- Skin biopsy, peri lesional
skin
- Desmosomal IgG/C3 +
•
Indirect
immunofluoresence
- Serum autoantibodies
- Titre correlates with
disease activity
Intercellular
desmosomal IgG and
C3, Fish net like
pattern
Bullous Pemphigoid
Pathogenesis
•
Circulating antibodies of IGG class bind to
pemphigoid antigens (BP 180, BP 230) on the
hemidesmosome of basement membrane, followed
by complement activation and formation of
subepidermal bullae.
Bullous Pemphigoid
Immunopathology
•
Direct
immunofluoresence
- Skin biopsy, perilesional
skin
- Linear deposit, IgG/C3
basement membrane
zone
•
Indirect
immunofluoresence
- Serum autoantibodies
- Does not correlate
with disease activity
Linear IgG and C3 at
Basement Membrane Zone
A Dermatitis Herpetiformis Case
•
35 year old with intensely
pruritic recurrent vesicles
arranged in groups (hence
the term herpetiformis).
Distributed symmetrically
over the extensor surfaces of
extremities and the trunk for
few years. He also has
gluten sensitive enteropathy
(celiac disease).
Dermatitis Herpetiformis
Image from Fitzpatrick’s Color Atlas of Clinical Dermatology, 5th ed
Dermatitis Herpetiformis
Pathogenesis
IgA binds to antigens in the bowel and
complexes, then circulate to bind to the
skin causing small subepidermal
vesicles.
• Skin biopsy and direct IMF are
diagnostic
•
- Granular IgA deposit at the dermal papillae
Understand 2 distinctly
different disorders under
Cutaneous Manifestations of
Systemic Disease
•
Erythema multiforme
- Stevens Johnson syndrome
•
Erythema nodosum
Erythema Multiforme
Target Lesions
Erythema nodosum
Deep painful
nodular lesions
Panniculitis, inflammation in subcutaneous fat
Erythema Nodosum
Panniculitis (inflammation of fat)
• Deep, firm and tender reddish-blue nodules,
1-5 cm, calves, shins and occasionally on
forearm
• Idiopathic (20%), Bacterial, viral, fungal
infections, drugs (sulphonamides, oral
contraceptives) systemic diseases (IBD,
sarcoidosis, Behcet’s disease, malignancy
(rare)
•