blooody wounds
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Adriana Acurio, M.D.
Pathology Department
Chicago Medical School
2012
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Blood Vessels PART II1. Vasculitis
2. Disorders of vascular hyperreactivity3. Vascular tumors
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VasculitisInflammation of the vessel wall with deleteriousconsequences on downstream tissues
Diverse disease group categorized by ETIOLOGY
and SIZE of vessel involvedThe most common etiologic mechanisms include:
1. Noninfectious (Immune-mediated inflammation)
2. Infectious (colonization by infectious pathogens)3. Physical/chemical injury (irradiation, mechanical
trauma, and toxins)
Distinction of etiology is important for
management
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Noninfectious VasculitisPathophysiologic mechanisms:
Immune complex deposition
1. Anti-neutrophil cytoplasmic antibodies2. Anti-endothelial cell antibodies
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Vessel Size Involvement
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Noninfectious Vasculitis
Immune Complex DepositionCirculating antigen-antibody complexes deposit invascular beds and cause an inflammatory response
Can be associated with:Autoimmune disorders Systemic Lupus Erythematosus
Drug hypersensitivities
PenicillinViral infections Hepatitis B virus
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Noninfectious Vasculitis:
Anti-Neutrophil Cytoplasmic AntibodiesANCAs are a diverse group of
autoantibodies directed againstneutrophils, monocyte lysosomes,and endothelial cells
They are classified based onintracellular distribution AND
target antigens:Perinuclear (p-ANCA):
Anti-myeloperoxidase (MPO-ANCA)
Cypolasmic (c-ANCA):
Anti-proteinase-3 (PR3-ANCA)
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ANCA titers are measured byELISA studies, type isdetermined by indirect
immunofluorescence Titers can reflect degree of
inflammatory activity andrecurrence (clinicalmanagement)
ANCAs directly activateneutrophils and stimulate
release of reactive oxygen speciesand proteolytic enzymes ~
endothelial cell dama e
Anti-Neutrophil Cytoplasmic Antibodies
Pathogenesis is poorlyunderstood ANCA production induced by
drugs or cross-reactivity
Predisposing inflammatory
stimuli upregulate MPO/PR3
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Noninfectious Vasculitis:
Anti-endothelial cell antibodiesIt is suspected that certain vasculitides are caused by
autoantibodies directed to endothelial cells in vessels
A prominent example is Kawsakis disease
For most vasculitidies, a specific causative agent has
not been defined. Therefore, site of involvement is avery important clue in diagnosis
P
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Capillaries
VenulesArterioles
Arteries Veins
Aorta
e um vesse vascu s
Immune complexmediated
(e.g., polyarten isnodosa)
Granulomas,no asthma(Wegener
granulomatosis)
Vasculitis withoutasthma or granulomas
(microscopicpolyangiitis)
Eosinophilia, asthma,and granulomas(Chrug-Strauss
syndrome)
Anti-endothelialcell antibodies
(e.g., Kawasakidisease)
Large vessel vasculitis
Paucit of immune com lexes often withANCA
_____________________ ,/ Small vesselvasculitis _______
Granulomatous disease(e.g., giant cell arterilis.
Takayasu arleritis)
Immune complex mediated
SLE IgA Cryoglobulin Other (e.g.,(e.g., SLE (e.g., Henoch- (e.g., cryoglobulin Goodpasturevasculitis) SchOnlein purpura) vasculitis) disease)
Kumar et al: Robbins & Cotran Pathologic Bass of Disease, 8th Edition.Copyright () 2009 by Saunders, an imprint of Elsevier, Inc. All rights reserved.
Vessel Size Involvement In VariousMOP
V a s c u l i t i d e sInvolvementIn-
Various
Vasa'Rides
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Giant-Cell (Temporal) ArteritisMost common form of vasculitis in the USAffects adults >50y, particularly elderly
Chronic, GRANULOMATOUS inflammation of:
Large vessels of the head (temporal, vertebral andophthalmic arteries)
Aorta
Ophthalmic arterial involvement can lead to
permanent blindness = medical emergencySensitive to treatment with corticosteroids and
anti-TNF in refractory cases (prompt diagnosis!)
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Giant-Cell (Temporal) Arteritis
Clinical FeaturesEtiology Uncertain, T cell response
against a vessel antigen,release of cytokines (TNF) andhumoral response mediated byanti-endotheilial antibodies
Morphologic Findings Granulomatous inflammation
of media
Intimal fibrosis Disruption of internal elastic
lamina
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Giant-Cell (Temporal) Arteritis
Clinical FeaturesSymptoms
Fever, fatigue, weight loss Headaches Facial pain Pain on palpation along the
course of the superficialtemporal artery
Ocular symptoms ranging fromdiplopia to complete vision lossare seen (ophthalmic artery
involvement, 50% of patients)Diagnosis Clinical findings Elevated ESR
Histologic confirmation
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Diagnosis: Clinical findings Elevated ESRTreatment:
Corticosteroids
Takayasu Arteritis
GRANULOMATOUS vasculitis ofmedium to large arteries, including the
Aorta
Aortic arch and great vessels (60%)
Distal aorta and branches (30%) Originally described in young females of
Japanese descent
Clinically and morphologically similar to
Giant-cell Aortitis, distinction = age: > 50 yo = Giant-cell aortitis
< 50 yo = Takayasu aortitis
Variable course, slow or rapid/
fulminant progression
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P
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Capillaries
VenulesArterioles
Arteries Veins
Aorta
e um vesse vascu s
Immune complexmediated
(e.g., polyarten isnodosa)
Granulomas,no asthma(Wegener
granulomatosis)
Vasculitis withoutasthma or granulomas
(microscopicpolyangiitis)
Eosinophilia, asthma,and granulomas(Chrug-Strauss
syndrome)
Anti-endothelialcell antibodies
(e.g., Kawasakidisease)
Large vessel vasculitis
Paucit of immune com lexes often withANCA
_____________________ ,/ Small vesselvasculitis _______
Granulomatous disease(e.g., giant cell arterilis.
Takayasu arleritis)
Immune complex mediated
SLE IgA Cryoglobulin Other (e.g.,(e.g., SLE (e.g., Henoch- (e.g., cryoglobulin Goodpasturevasculitis) SchOnlein purpura) vasculitis) disease)
Kumar et al: Robbins & Cotran Pathologic Bass of Disease, 8th Edition.Copyright () 2009 by Saunders, an imprint of Elsevier, Inc. All rights reserved.
Vessel Size Involvement In VariousMOP
V a s c u l i t i d e sInvolvementIn-
Various
Vasa'Rides
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Polyarteritis Nodosa (PAN)Affects all ages, typically young adultsVariable clinical course, episodic with
long disease-free intervals
Clinical Findings:
Peripheral neuritis/ ischemia Hypertension (renal vessels)
Abdominal pain and melena (GI)
Renal failure (major cause of death)
Untreated it is fatal, often duringfulminant acute attackTreatment based on corticosteroids and
cyclophosphamide, 90% effective
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Polyarteritis Nodosa (PAN)
Acute stage: Transmuralinflammation (neutrophils,eosinophils, and mononuclear
cells) and fibrinoid necrosis andthrombosis
Chronic stage: fibrous thickening(scarring) of the vessel wall
Different stages can be seen in agiven patient
Weakening of arterial wall byinflammation leads to aneurysms,
impaired perfusion and ischemia
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Vascular thrombosis and
MI (trichrome stain)
Kawasaki Disease- Clinical Features
Clinical Findings: Conjunctival and oral erythema/ulcer
Edema of hands and feet witherythema of the palms and soles
Desquamative rash
Cervical lymphadenopathy Up to 20% of untreated patients
develop cardiovascular disease:
Aneurysm/rupture of coronary vessels
Thrombosis
Myocardial infarction, sudden death
Treatment with intravenous Igtherapy and aspirin, reducesrate of coronary artery diseaseto
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Capillaries
VenulesArterioles
Arteries Veins
Aorta
e um vesse vascu s
Immune complexmediated
(e.g., polyarten isnodosa)
Granulomas,no asthma(Wegener
granulomatosis)
Vasculitis withoutasthma or granulomas
(microscopicpolyangiitis)
Eosinophilia, asthma,and granulomas(Chrug-Strauss
syndrome)
Anti-endothelialcell antibodies
(e.g., Kawasakidisease)
Large vessel vasculitis
Paucit of immune com lexes often withANCA
_____________________ ,/ Small vesselvasculitis _______
Granulomatous disease(e.g., giant cell arterilis.
Takayasu arleritis)
Immune complex mediated
SLE IgA Cryoglobulin Other (e.g.,(e.g., SLE (e.g., Henoch- (e.g., cryoglobulin Goodpasturevasculitis) SchOnlein purpura) vasculitis) disease)
Kumar et al: Robbins & Cotran Pathologic Bass of Disease, 8th Edition.Copyright () 2009 by Saunders, an imprint of Elsevier, Inc. All rights reserved.
Vessel Size Involvement In VariousMOP
V a s c u l i d i t e sInvolvementIn-
Various
Vasculidites
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Microscopic Polyangiitis
NECROTIZING vasculitis of capillaries, arterioles and venules Broad systemic involvement of skin, mucous membranes,
lungs, brain, heart, gastrointestinal tract, kidneys, and muscle
Necrotizing glomerulonephritis (90%) and pulmonary
capillaritis (60%) are common Pathogenesis:
Associated with MPO-ANCAs (p-ANCAs)
Immune complex deposition: Antibody response
to drug(e.g., penicillin), bacterial (e.g., streptococci),protein antigens
Manifestations are attributed to recruitment andactivation of neutrophils
Cyclophosphamide and steroids lead to
remission (renal and
brain involvement are difficult to treat)
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brain involvement are difficult to treat)
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Wegner Granulomatosis Clinical Features:
Males > females, usually in their 40s Chronic sinusitis Nasopharyngeal ulceration Persistent pneumonitis Renal disease (80%): hematuria, failure Rashes, muscle pains, articular involvement,
neuritis and fever
Responds to immunosuppressive
therapy, 80% of untreated patients diewithin 1 year
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Wegner GranulomatosisMorphologic Features:
Necrotizing granulomas arecharacteristic (central necrosis,fibroblastic proliferation, giant
cell reaction and mononuclearinfiltrate)
In the kidney, the inflammationaffects the glomeruli,
progressing formfocal/segmental to diffusecrescentic glomerulonephritis
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progression Arterial acute and chronic inflammation with luminalh b d d
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progression thrombosis can extend into contiguous veins and nervesresulting in fibrous scarring of all three structures
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Vasculitis Associated with Other
DiseasesImmunologic disease
Rheumatoid arthritis
SLE
Mixed cryoglobulinemia
Antiphospholipid antibody syndrome
Henoch-Schnlein purpura
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Infectious Vasculitis
Vessel wall inflammation due to colonization byinfectious pathogens (bacteria/fungi)
Subsequent immune complex deposition and
antibody cross-reactivity can occurCan lead to weakening of vessel wall and mycotic
aneurysms
Examples:
Bacterial pneumonia pulmonary hemorrhage
Bacterial meningitis - brain infarction
Aspergillus and Mucor - vasoinvasive fungal sp.
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Raynaud Phenomenon
Recurrent vasospasms of the fingers and toes inresponse to stress or cold
Primary Raynaud (Raynaud disease): Vasospasmwith no association with systemic illness
Secondary Raynaud phenomenon: Vasospasmassociated with other illness (autoimmune disease).Most common associations:Scleroderma (90%)
Mixed connective-tissue disease (85%)
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Raynaud Phenomenon
Patients often describe 3 phases of color change:
Intial white (vasoconstriction)
followed by blue (cyanosis)
red (rapid blood reflow)
Changes are reversible, must be distinguishedfrom irreversible causes of ischemia such as
vasculitis or thrombosisMost commonly affects fingers and toes but may
affect nose, ears and tongue
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Raynaud Phenomenon
Pathophysiology: UnknownStructural vessel wall abnormalities
and deficiencies in autonomiccontrol cause recurrent
vasoconstriction followed byimpared vasodilation of cutaneous
vessels in the prescence of stressfulstimuli
Epidemiology: Slightly moreprevalent in women in the 2ndor 3rd
decades
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Vascular Tumors
Benign Neoplasms, Developmental and Acquired Conditions
HemangiomaCapillary hemangiomaCavernous hemangioma
Lymphangioma
Simple (capillary) lymphangiomaCavernous lymphangioma (cystic hygroma)
Glomus tumor
Vascular ectasiasNevus flammeus
Spider telangiectasia (arterial spider)Hereditary hemorrhagic telangiectasis (Osler-Weber-Rendu disease)
Reactive vascular proliferationsBacillary angiomatosis
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Hemangioma
Tumors of blood-filled vessels, often present at birth
Most commonly seen in the head and neck, can alsopresent in internal organs such as liver
Their classification is based on histologic appearanceCapillary Hemangiomas: Strawberry Hemangiomas (newborn) Pyogenic Granulomas
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HemangiomaCavernous Hemangiomas:
Composed of larger vascular channels
Circumscribed, locally destructive, do not regress
In von Hippel-Lindau disease, they present in retina,central nervous system, pancreas, liver
Retinal cavernous hemangioma in patient with von Hippel-Lindau disease
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Bacillary Angiomatosis
Vascular proliferation secondary to Bartonella infectionaffecting immunosuppressed patients
Can involve the skin, bone, brain, and other organs. Twospecies have been implicated:
Bartonella henselae (cat-scratch disease)
Bartonella quintana ("trench fever transmitted by body lice)
Bacillary angiomatosis in patient with AIDS (silver stain highlighting bacilli)
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Vascular TumorsIntermediate-Grade Neoplasms
Kaposi sarcoma
HemangioendotheliomaMalignant Neoplasms
Angiosarcoma
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Angiosarcoma
Malignant vascular neoplasms composed of rapidlyproliferating, extensively infiltrating anaplastic cells
It is a rare malignancy showing association to special
settings:Hepatic angiosarcomas associated with exposure to vinyl
chloride monomer (VCM) in polyvinyl chloride (PVC)polymerization plants as well as arsenic-containing
insecticides and ThorotrastCutaneous angiosarcoma of breast after lumpectomy,
axillary lymph node dissection, and radiotherapy forprimary breast carcinoma
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Angiosarcoma
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