Patterns and mechanisms of inflammatory skin conditions: the pathologist s survival kit SALVADOR J. DIAZ-CANO BAHRAIN, APRIL 2017
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1 Patterns and mechanisms of inflammatory skin conditions: the pathologist s survival kit SALVADOR J. DIAZ-CANO BAHRAIN, APRIL 2017
2 Basic Elements of Lesions
3 Repair Injury Time & Intensity Cell damage oncosis Hyperplastic reaction Cell damage cytopathic Combined Inflammatory cellular Inflammatory Extracellular/vascular
4 Biological Basis of Elementary Lesions Cellular response Cell perpetuation pathway Cell differentiation pathway Activation of default pathway cell death Tissue effects Parenchyma and stroma interactions Combination of findings depending on the primary damage target
5 Biological Processes and Pathology Primary Biological Process Increased keratinocyte turnover Decreased keratinocyte turnover Inflammation Cell damage General Pathology Hyperplastic changes Lack of full cell differentiation Relative increase of cell loss Relative atrophy Full cell differentiation Decreased cell loss Vascular changes and permeability Cellular infiltrate Cell damage (stroma, vessels, epithelia) Reversible Irreversible Regeneration and reparation
6 Psoriasiform Acanthosis Dermatophytosis Psoriasis Seborrheic dermatitis Allergic contact / nummular dermatitis PRP Secondary syphilis Scabies, Norwegian type MF
7 Psoriasiform Dermatitis Neutrophils within parakeratosis Superficial perivascular dermatitis Psoriasis
8 Irregular Epidermal Hyperplasia Pseudoepitheliomatous hyperplasia Suppurative granulomatous dermatitis Deep mycosis, atypical mycobacterias
9 Markedly Thinned Epidermis Dermatomyositis/DLE DLE GVHD LP, atrophic LP-like keratosis Porokeratosis Lichen sclerosus Degos disease
10 Interface Dermatitis Leukocyte infiltration of the dermis Vacuolar change of basilar epidermis Papillary dermal melanophages Necrosis of keratinocytes AKA: lichenoid tissue reaction pattern, vacuolar interface dermatitis
11
12 Lichenoid Interface Dermatitis Wedge-shaped hypergranulosis Lichenoid infiltrate Lichen planus
13 Vacuolar Interface Dermatitis Necrotic keratinocytes Vacuolar alteration Lichenoid inflammation Superficial perivascular lymphohistiocytic Erythema Multiforme
14 Spongiotic Dermatitis Spongiosis around acrosyringia Miliaria rubra
15 Eosinophilic Spongiosis BP/HG, urticarial Allergic dermatitis Pemphigus vulgaris, urticarial Arthropod assault Dermatophytosis Incontinentia pigmenti, vesicular Toxic erythema of newborn
16 Lymphocytic Infiltrate DLE, tumid Pernio PLE Insect bite Erythema figuratum
17 Perivascular Lymphoplasmacytic Infiltrate Acrodermatitis chronica atrophicans Erythema chronicum migrans Secondary syphilis Necrobiosis lipoidica Morphea
18 Exocytosis vs. Epidermotropism EXOCYTOSIS EPIDERMOTROPISM Random through epidermis to surface Spongiotic tissue reaction Inflammatory processes Lower third/half epidermis Tendency to aggregate No/little spongiosis Feature of MF
19 Superficial and Deep Inflammation Light reaction Lymphoma Leprosy Lues Lichen striatus Lupus erythematosus Lipoidica (necrobiosis) Lepidoptera (+ other arthropods) Dermatophyte Reticular erythematous mucinosis Urticarial stages (BP) Gyrate erythemas Scleroderma (localized) Drug reactions 8Ls + DRUGS
20 Nodular Dermatitis Germinal centers in a dense nodular or diffuse infiltrate Delayed hypsersensitivity reaction
21 Abnormal Lymphocytes in Mixed Cell Infiltrate Tick bite reaction Herpesvirus Dermatophytosis Ruptured molluscum Kikuchi s disease Gianotti-Crosti Lymphomatoid papulosis MF
22 Dense Mixed Inflammation Granuloma faciale / Erythema elevatum diutinum Nodular scabies Tick bite reaction
23 Subcorneal Pustule Dermatophytosis Candidiasis Impetigo Suppurative infundibulitis Pemphigus foliaceus Pustular psoriasis Prurigo pigmentosa
24 Papillary Micro-abscesses DH / linear IgA dermatitis, drug eruptions Acquired EB DLE Bullous LE LCC vasculitis
25 Interstitial Neutrophils in Reticular Dermis Urticaria Cutis laxa DH / linear IgA dermatitis Bullous LE Fixed drug eruption Cellulitis Flea bite Pustular infundibular dermatitis LCC vasculitis Sweet s / PG Lymphomatoid papulosis
26 Cytopathic Dermatitis Acantholytic separation Multinucleated epithelial giant cells Herpesvirus infections
27 Ballooning EM Fixed drug eruption Mucha-Haberman Prurigo pigmentosa Hand-foot-mouth disease Herpesvirus Milker s nodule/orf Irritant contact dermatitis Burn
28 Fibrosing Dermatitis Thinned epidermis Thickened edematous / sclerotic papillary dermis Underlying mononuclear infiltrate Lichen sclerosus
29 Fibrosing Dermatitis Decreased number of adnexal structures Fibrosing inflammatory of neoplastic conditions
30 Elements of Pattern Recognition With/without epidermal changes Spongiotic, interface, hyperplastic, atrophic Distribution of inflammatory infiltrate Topography Superficial vs. superficial & deep Microanatomy Perivascular, interstitial, nodular, diffuse Type of inflammatory infiltrate Mononuclear Lymphocytes ± histiocytes Mixed Mono- and polymorphonuclear Polymorphonuclear ± eosinophils
31 Approach to Microscopic Diagnosis
32 Cytopathic dermatitis Psoriasiform dermatitis Intraepidermal bullous dermatitis Lichenoid dermatitis Vacuolar dermatitis Spongiotic dermatitis Subepidermal bullous dermatitis
33 Approach to Microscopic Diagnosis (2)
34 Vasculitides - dermatitis Nodular dermatitis Fibrosing dermatitis Perivascular dermatitis Diffuse dermatitis
35 Lesions by Topography Adnexal structures Folliculitis and perifolliculitis Follicular lesions with alopecia Subcutaneous soft tissue Panniculitis
36 Folliculitis Septal panniculitis Perifolliculitis Lobular panniculitis
37 Perifolliculitis Peri-infundibular and perifollicular fibroplasia Long-standing perifolliculitis (traction alopecia, LPP)
38 Non-scarring Alopecia Catagen or telogen follicles NO inflammatory infiltrate Other findings: Plucked hair All telogen hairs Common baldness, telogen effluvium, trichotillomania
39 Mostly Septal Panniculitis Miescher s radial granuloma Linear spaces containing lipids Tiny collections of neutrophils Palisading histiocytes Erythema nodosum
40 Mostly Lobular Panniculitis Arteritis Fat necrosis Suppuration Granulomas Fibrosis Nodular vasculitis
41 Cell-Poor Subepidermal Blister Suction blister Gas gangrene Porphyria cutanea tarda Bullous dermatosis of hemodialysis Bullous amyloid Blister above scar Hypoxemia blister Electric current Second-degree burn Bullous pemphigoid EB Darier s disease, systematized epidermal nevus Grover s disease Porokeratosis Solar keratosis
42 Antigen Presentation, Inflammation & Hypersensitivity
43 Antigen Processing
44 Inflammatory and Cellular Response after Injury
45 Mediator release Necrosis Mediator release Adhesion Soluble complexes Ag-Ab complex transfer CYTOTOXIC INACTIVATION ANAPHYLACTIC CELL-MEDIATED CYTOTOXICITY DELAYED HYPERSENSITIVITY GRANULOMATOUS REACTION
46 Interstitial Granulomatous Infiltrate Granuloma annulare Dermatofibroma Interstitial granulomatous dermatitis Necrobiosis lipoidica MF, interstitial type MF (granulomatous slack skin)
47 Palisaded Granuloma Granuloma annulare Gout Rheumatoid nodule Interstitial granulomatous dermatitis Necrobiosis lipoidica Necrobiotic xanthogranuloma
48 Sarcoidal granulomas Sarcoidal granulomatous pattern Cohesive epithelioid histiocytes Few or no lymphocytes Sarcoidosis, hallogenoderm
49 Tuberculoid granulomas Tuberculoid granulomatous pattern Collections of epithelioid histiocytes Lymphocytes and plasma cells Mycobacterial infections, leishmania, subcutaneous sarcoid
50 Suppurative granulomas Suppurative granulomatous inflammation Neutrophils and necrotic debris Histiocytes Few or no lymphocytes Rupture infundibular cyst, sporotrichosis, dermatophytes
51 Vasculitis Neutrophils, nuclear dust and fibrin in small blood vessel walls Leukocytoclastic vasculitis
52 Vasculitis Neutrophils, nuclear dust and fibrin in small blood vessel walls Thrombi within their lumina Septic vasculitis
53 Psoriasiform Dermatitis
54 Vacuolar Interface Dermatitis
55 Lichenoid Interface Dermatitis
56 Spongiotic Dermatitis
57 Superficial PV Dermatitis
58 Nodular Dermatitis
59 Granulomatous Dermatitis
60 Fibrosing Dermatitis
61 Mostly Septal Panniculitis
62 Mostly Lobular Panniculitis
63 Pathology for ADR Evaluation Confirmation of Drug Etiology Patterns and Mechanisms Prognosis/Activity Eosinophils Necrotic keratinocytes Vascular changes Endothelial prominence Hyperpermeability Exanthematous Extrinsic vascular Spongiotic Vesiculo-spongiotic Intrinsic vascular ± granulomas Vesiculopustular ± lichenoid or psoriasiform component Extension of necrosis: Confluent or not Neutrophilic exocytosis: Isolated / Pustular Vascular damage: IVR, vasculitis Extension of inflammation: PV, interstitial, nodular, diffuse
64 a b c d
65 Patterns: Common Basic and Secondary Exanthematous Psoriasiform Lichenoid Commonest pattern Basic profile Chronicity Relative low risk Common as secondary pattern Certain drugs if pseudoepitheliomatous Chronicity Relative low risk Common as secondary pattern
66 Epithelial Damage and Necrosis Basal cells Multifocal Confluent Isolated, cytotoxic Barrier effect maintained Clustering, cytotoxic Barrier effect maintained Multifactorial Barrier effect lost
67 Vascular Changes and Damage Perivascular IVR Vasculitis Basic profile Permeability Minor vessel wall damage Permeability Major vessel wall damage
68 a b c d
69 Neutrophilic Activity Perivascular Single cell exocytosis Pustular Basic profile Spongiosis No keratinocyte damage/necrosis Spongiosis With keratinocyte damage/necrosis
70 Infiltrate Extension Basic - Perivascular PV + Interstitial Nodular Diffuse Low grade progressive Severe Severe & Tissue Damaging
71 Type I Hypersensitivity
72 IgG4-mediated Reactions
73 Inflammatory Skin Lesions Patterns are the result of the interaction of injury agents and tissue response, modulated in intensity and time Elementary lesions will depend on: basic epidermal reaction (based on cellular turnover and maturation), vascular and cellular inflammatory components, types of cells, and distribution of cells (topography and microanatomy) Activity should be evaluated a from target damage (epithelial necrosis, vasculitis), exocytosis (neutrophilic), and density of infiltrate Morphological and clinico-pathologic correlation should be included in the conclusion
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