VASCULAR PATHOLOGY

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VASCULAR PATHOLOGY By By DR. OLA OMRAN DR. OLA OMRAN ASSOCIATE PROFESSOR ASSOCIATE PROFESSOR PATHOLOGY CONSULTANT PATHOLOGY CONSULTANT PATHOLOGY DEPARTMENT PATHOLOGY DEPARTMENT

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VASCULAR PATHOLOGY. By DR. OLA OMRAN ASSOCIATE PROFESSOR PATHOLOGY CONSULTANT PATHOLOGY DEPARTMENT. VASCULITIS. DEFINITION: It means “ inflammation of the walls of the vessels ” and can be associated to many different clinical conditions - PowerPoint PPT Presentation

Transcript of VASCULAR PATHOLOGY

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VASCULAR PATHOLOGY

ByBy

DR. OLA OMRANDR. OLA OMRAN

ASSOCIATE PROFESSORASSOCIATE PROFESSOR

PATHOLOGY CONSULTANTPATHOLOGY CONSULTANT

PATHOLOGY DEPARTMENTPATHOLOGY DEPARTMENT

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VASCULITISDEFINITION:DEFINITION: It means “inflammation of the walls of the vessels” and can be It means “inflammation of the walls of the vessels” and can be

associated to many different clinical conditions associated to many different clinical conditions

20 primary forms of vasculitis are recognized20 primary forms of vasculitis are recognized

ClassificationsClassifications according to vessel sizeaccording to vessel size, , role of immune role of immune complexes, presence of specific autoantibodiescomplexes, presence of specific autoantibodies, , granuloma granuloma formationformation, , organ tropismorgan tropism, and even , and even population demographicspopulation demographics. .

Several vasculitides tend to Several vasculitides tend to affect only vessels of particular affect only vessels of particular caliber or tissue bedscaliber or tissue beds

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VASCULITIS

The two most common pathogenic mechanisms of vasculitisThe two most common pathogenic mechanisms of vasculitis are:are:

1.1. immune-mediated inflammation immune-mediated inflammation

2.2. direct invasion of vascular walls by infectious pathogens.direct invasion of vascular walls by infectious pathogens. Predictably, infections can also indirectly induce a Predictably, infections can also indirectly induce a noninfectious vasculitis, for example, by noninfectious vasculitis, for example, by generating generating immune complexesimmune complexes or or triggering cross-reactivitytriggering cross-reactivity. .

3.3. Physical and chemical injuryPhysical and chemical injury, such as from irradiation, , such as from irradiation, mechanical trauma, and toxins, can also cause vasculitis. mechanical trauma, and toxins, can also cause vasculitis.

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VASCULAR PATHOLOGY VASCULITIS

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CLASSIFICATION OF VASCULITIS BASED ON THE CLASSIFICATION OF VASCULITIS BASED ON THE PATHOGENESIS: PATHOGENESIS:

*Direct Infection. *Direct Infection. --Bacterial(Neisseria) Bacterial(Neisseria)

-Rickettsial(spotted fever) -Rickettsial(spotted fever) -Spirochetal(Syphilis) -Spirochetal(Syphilis) -Fungal(aspergillosis) -Fungal(aspergillosis) -Viral(herpes zoster) -Viral(herpes zoster)

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*Immunologic. *Immunologic. A. A. Immune complex- mediatedImmune complex- mediated. . --Infection-Infection-

induced(Hepatitis B,C) induced(Hepatitis B,C) -Henoch-Schonlein -Henoch-Schonlein purpura purpura -SLE, etc. -SLE, etc. --Drug-inducedDrug-induced -Cryoglobulinemia(Ig, IgM) -Cryoglobulinemia(Ig, IgM) --Serum sicknessSerum sickness

B. B. ANCA-mediatedANCA-mediated. . --Wegener Wegener granulomatosis granulomatosis -Microscopic -Microscopic polyangeitis polyangeitis -Churg-Strauss -Churg-Strauss syndrome syndrome

C. C. Direct Ab-induced Direct Ab-induced --Goodpasture syndrome(anti-GBM Abs) Goodpasture syndrome(anti-GBM Abs) -Kawasaki -Kawasaki disease(anti-endoth.Ab)disease(anti-endoth.Ab)

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VASCULAR PATHOLOGY

DD. Cell-mediated. . Cell-mediated. -Organ-allograft rejection -Organ-allograft rejection -Inflammatory bowel disease -Inflammatory bowel disease -Paraneoplastic vasculitis -Paraneoplastic vasculitis

*Unknown. *Unknown. --Giant.cell arteritis Giant.cell arteritis -Takayasu arteritis -Takayasu arteritis --Polyarteritis nodosaPolyarteritis nodosa

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Noninfectious Vasculitis (immune-mediated inflammation)

Immune complex deposition 1.  Vasculitis associated with 1.  Vasculitis associated with drug hypersensitivity drug hypersensitivity (e.g., penicillin), (e.g., penicillin), antibodies directed antibodies directed

against the drug-modified self proteins against the drug-modified self proteins lead to lead to the formation of immune complexesthe formation of immune complexes. . Manifestations frequently involving the Manifestations frequently involving the skinskin and can be and can be mild and self-limitingmild and self-limiting or or severe and severe and

even fataleven fatal. . Discontinuation of the offending agent is often curative.Discontinuation of the offending agent is often curative.

2. vasculitis associated with 2. vasculitis associated with viral infectionsviral infections, , antibody to viral proteinsantibody to viral proteins may form may form immune immune complexescomplexes detectable in the serum and in the vascular lesions; for example, as many as detectable in the serum and in the vascular lesions; for example, as many as 30% of 30% of patients with patients with polyarteritis nodosa polyarteritis nodosa have an underlying hepatitis B infection have an underlying hepatitis B infection with vasculitis with vasculitis attributable to attributable to complexes of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg.complexes of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg.

  

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2. Antineutrophil Cytoplasmic Antibodies (ANCA):

  Many patients with vasculitis have Many patients with vasculitis have circulating antibodiescirculating antibodies that that react with react with neutrophil cytoplasmic antigens,neutrophil cytoplasmic antigens, so-called ANCAs. so-called ANCAs.

ANCAs are ANCAs are a heterogeneous group of autoantibodies directed against a heterogeneous group of autoantibodies directed against constituents (mainly enzymes) of neutrophil primary granules, monocyte constituents (mainly enzymes) of neutrophil primary granules, monocyte lysosomes, and endothelial cells.lysosomes, and endothelial cells.

Two general types of ANCAs based on immunofluorescence staining Two general types of ANCAs based on immunofluorescence staining patterns: patterns:

1.1. Cytoplasmic localization (c-ANCA),Cytoplasmic localization (c-ANCA), wherein the most common target antigen wherein the most common target antigen is p roteinase-3 (PR3), a neutrophil granule constituentis p roteinase-3 (PR3), a neutrophil granule constituent

2.2. Perinuclear localization (p-ANCA),Perinuclear localization (p-ANCA), wherein most of the autoantibodies are wherein most of the autoantibodies are specific for myeloperoxidase (MPO). specific for myeloperoxidase (MPO).

c-ANCA in c-ANCA in Wegener granulomatosisWegener granulomatosis & & p-ANCA in p-ANCA in microscopic polyangiitis microscopic polyangiitis and Churg-Strauss syndromeand Churg-Strauss syndrome. .

  ANCAs is ANCAs is useful quantitative diagnostic markers for the ANCA-associated useful quantitative diagnostic markers for the ANCA-associated vasculitidesvasculitides, and , and their levels reflect the degree of inflammatory activitytheir levels reflect the degree of inflammatory activity . .

  Although the mechanisms are unknown, Although the mechanisms are unknown, ANCAsANCAs can directly can directly activate activate neutrophilsneutrophils and stimulates neutrophils to and stimulates neutrophils to release reactive oxygen speciesrelease reactive oxygen species and and proteolytic enzymesproteolytic enzymes. .

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3. Anti-Endothelial Cell Antibodies

Antibodies to ECs may predispose to certain Antibodies to ECs may predispose to certain vasculitides, for example vasculitides, for example Kawasaki disease. Kawasaki disease.

Another ClassificationsAnother Classifications according to vessel according to vessel size:……… size:………

  

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Vasculitis type* Examples DescriptionLarge-Vessel Vasculitis (Aorta and Large Branches to Extremities, Head, and Neck)

Giant-cell (temporal) arteritis

Granulomatous inflammation; also frequently involves the temporal artery. Usually occurs in patients older than age 50 and is associated with polymyalgia rheumatica.

  Takayasu arteritis

Granulomatous inflammation usually occurring in patients younger than age 50

Medium-Vessel Vasculitis (Main Visceral Arteries and Their Branches)

Polyarteritis nodosa

Necrotizing inflammation typically involving renal arteries but sparing pulmonary vessels

  Kawasaki disease Arteritis with mucocutaneous lymph node syndrome; usually occurs in children. Coronary arteries can be involved with aneurysm formation and/or thrombosis.

Small-Vessel Vasculitis (Arterioles, Venules, Capillaries, and Occasionally Small Arteries)

Wegener granulomatosis

Granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small vessels, including glomerulonephritis. Associated with c-ANCAs.

  Churg-Strauss syndrome

Eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small vessels. Associated with asthma and blood eosinophilia. Associated with p-ANCAs.

  Microscopic polyangiitis

Necrotizing small-vessel vasculitis with few or no immune deposits; necrotizing arteritis of small and medium-sized arteries can occur. Necrotizing glomerulonephritis and pulmonary capillaritis are common. Associated with p-ANCAs.

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1. GIANT CELL (TEMPORAL) ARTERITIS.

MOST common form of systemic vasculitis MOST common form of systemic vasculitis Adults males over 50ys Adults males over 50ys acute or chronic acute or chronic large sized vessels ( affects temporal arteries, large sized vessels ( affects temporal arteries,

ophtalmic(blindness) and aorta (aneurysm) ophtalmic(blindness) and aorta (aneurysm)

GP: tender, nodular thickening of the arteryGP: tender, nodular thickening of the artery reduction of the reduction of the lumenlumenthrombosis. thrombosis.

MP: Granulomatous inflammation in inner half of media with MP: Granulomatous inflammation in inner half of media with giant cells. giant cells.

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Thickened, nodular, and tender arteries

GIANT CELL (TEMPORAL) ARTERITIS.

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Temporal (giant cell) arteritis

thickened, nodular, and tender segment

Giant cells & granuloma at the degenerated internal elastic membrane in active arteritis H&E

Elastic tissue stain demonstrating focal destruction of internal elastic membrane (arrow) and intimal thickening (IT) characteristic of long-standing or healed arteritis

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Elastic tissue stainElastic tissue stain demonstrating:demonstrating:

focal destruction of focal destruction of internal elastic internal elastic membranemembrane ( (arrowarrow) ) and and

intimal thickeningintimal thickening ((ITIT) characteristic of ) characteristic of long-standing or long-standing or healed arteritis.healed arteritis.

Giant cell arteritis

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GIANT CELL ARTERITIS...(cont.)

CLINICAL FEATURES: CLINICAL FEATURES: Old patients with fever, fatigue, loss of weight, Old patients with fever, fatigue, loss of weight,

with or w/o facial pain and headache. with or w/o facial pain and headache. More severe form ….involvement of ophtalmic More severe form ….involvement of ophtalmic

artery artery diplopia or blindness of abrupt onset. diplopia or blindness of abrupt onset.

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2. TAKAYASU ARTERITIS.

Predominant in females Predominant in females below 50´s below 50´s Propable autoimmune mechanismPropable autoimmune mechanism, , characterized by ocular manifestations/weakness of characterized by ocular manifestations/weakness of

pulses in upper extremities (reduced brachial pulse), pulses in upper extremities (reduced brachial pulse), due to vasculitis of due to vasculitis of Aortic Arch Aortic Arch + branches + branches narrowing narrowing obliteration. obliteration.

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MICROSCOPIC: MICROSCOPIC: Mononuclear infiltration of adventecia.Mononuclear infiltration of adventecia. Giant-cell granulomatous inflammation NOT Giant-cell granulomatous inflammation NOT

distinguishable from giant-cell arteritis. distinguishable from giant-cell arteritis.

CLINICAL: CLINICAL: Reduced brachial pulse, difference in BP between R Reduced brachial pulse, difference in BP between R

& L arm>10 mm Hg, coldness+ numbness of & L arm>10 mm Hg, coldness+ numbness of fingers,, fingers,,

Visual defects Visual defects blindness. blindness.

TAKAYASU ARTERITIS...(cont.)

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Takayasu arteritis A,A, Aortic arch angiogram showing Aortic arch angiogram showing

narrowing of the brachiocephalic, narrowing of the brachiocephalic, carotid, and subclavian arteries carotid, and subclavian arteries ((arrowsarrows). ).

B,B, Gross photograph of two cross- Gross photograph of two cross-sections of the right carotid artery sections of the right carotid artery demonstrating marked intimal demonstrating marked intimal thickening with minimal residual thickening with minimal residual lumen. lumen.

C,C, Destruction and fibrosis of the Destruction and fibrosis of the arterial media and an infiltrate of arterial media and an infiltrate of mononuclear inflammation, mononuclear inflammation, including giant cells. including giant cells.

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3. POLYARTERITIS NODOSA (PAN).

Medium sized arteritis affecting multiple organs Medium sized arteritis affecting multiple organs (skin, peripheral nerves, gut, kidney and heart. (skin, peripheral nerves, gut, kidney and heart.

Childhood Childhood late adulthood (average 40 ys) late adulthood (average 40 ys) Associated with Hepatitis B, C or both (most Associated with Hepatitis B, C or both (most

common in injection drug abusers).common in injection drug abusers). Probably mediated by immune complexes Probably mediated by immune complexes

(Igs + viral Ags) (Igs + viral Ags) circulating and circulating and deposited in inflammed vessels.deposited in inflammed vessels.

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3. POLYARTERITIS NODOSA (PAN). ...(cont.)

CLINICAL FEATURES:CLINICAL FEATURES: Onset is gradual (wks Onset is gradual (wks mos.) mos.) Non specificNon specific: malaise,fever, weight loss, abdominal pain, : malaise,fever, weight loss, abdominal pain,

melena, myalgias, muscular weakness, diastolic pressure >90 melena, myalgias, muscular weakness, diastolic pressure >90 mm Hg, mm Hg,

Specific:Specific: Renal involvementRenal involvementhypertensionhypertension GI tractGI tract abdominal angina (hemorrhage, perforation). abdominal angina (hemorrhage, perforation). heart: myocarditis/myocardial infarction.heart: myocarditis/myocardial infarction. Eye: scleritis. Eye: scleritis.

About 1/3 of patients About 1/3 of patients HBAb+. HBAb+.

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POLYARTERITIS NODOSA..(cont.)

Diagnosis:Diagnosis:

*Elevated BUN or creatinine *Elevated BUN or creatinine

*Proven hepatitis B/C virus infection *Proven hepatitis B/C virus infection *Angiographic signs of aneuryms/vascular *Angiographic signs of aneuryms/vascular

occlusion (60% sensitive) occlusion (60% sensitive) *MP: Demonstration of necrotizing inflammation *MP: Demonstration of necrotizing inflammation

(segmental fibrinoid necrosis) & granulocytes in (segmental fibrinoid necrosis) & granulocytes in medium sized vessels (biopsy). medium sized vessels (biopsy).

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Polyarteritis nodosaPolyarteritis nodosa There is segmental There is segmental fibrinoid necrosis fibrinoid necrosis and and thrombotic occlusion of the lumen thrombotic occlusion of the lumen of this of this

small artery. small artery. Note that part of the vessel wall at the upper right (arrow) is uninvolvedNote that part of the vessel wall at the upper right (arrow) is uninvolved

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4. WEGENER´S GRANULOMATOSIS.

Granulomatous inflammation & necrotizing vasculitis Granulomatous inflammation & necrotizing vasculitis Average age is about 40 yrs. Average age is about 40 yrs. Affects Affects upper respiratory tract, lower respiratory tract upper respiratory tract, lower respiratory tract

and kidneys. and kidneys. Other organs affected: Other organs affected:

Eye (proptosis/diplopia), Eye (proptosis/diplopia), Skin (ulcers, purpura)Skin (ulcers, purpura) It may remain localized to one site for yrs./mos. It may remain localized to one site for yrs./mos.

systemic later (fever, fatigue, loss of weight, anemia, systemic later (fever, fatigue, loss of weight, anemia, leukocytosis andleukocytosis and increasedincreased ESRESR

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4. WEGENER´S GRANULOMATOSIS….CONTCLINICAL FEATURES: CLINICAL FEATURES:

*Chronic sinusitis(90%) *Chronic sinusitis(90%) *Chronic pneumonitis in about 95% of patients.*Chronic pneumonitis in about 95% of patients. *Mucosal ulcerations of nasopharynx (75%) *Mucosal ulcerations of nasopharynx (75%) *Renal disease (80%)*Renal disease (80%)

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WEGENER´S GRANULOMATOSIS

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Wegener granulomatosis inflammation of a small artery along with adjacent

granulomatous inflammation, in which epithelioid cells and giant cells (arrows)

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5. BUERGER´S DISEASE (Thromboangiitis obliterans)

Characterized by segmental thrombosis + Characterized by segmental thrombosis + acute / chronic inflammation of medium and acute / chronic inflammation of medium and small arteries MOSTLY tibial and radial ar teries, small arteries MOSTLY tibial and radial ar teries, and secondarily involvement of veins and secondarily involvement of veins and nerves of limbs. and nerves of limbs.

Apparently heavy cigarette-smokers are MOST frequently Apparently heavy cigarette-smokers are MOST frequently affected (endoth. cells hypersensitivity?) affected (endoth. cells hypersensitivity?)

Moreover Moreover increased prevalence of HLA-A9/ increased prevalence of HLA-A9/ HLA-B5 in these patients and in Israel, Japan, HLA-B5 in these patients and in Israel, Japan, India (genetic trait?)India (genetic trait?)

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Buerger disease The lumen is occluded by a thrombus containing two abscesses (arrows). The vessel wall is infiltrated with leukocytes.

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BUERGER´S DISEASE..(cont.)

Microscopically: Microscopically: acute + chronic inflammation in arterial walls + acute + chronic inflammation in arterial walls +

thrombosisthrombosisorganization/recanalization. Also, organization/recanalization. Also, thrombosis contains microabscesses + thrombosis contains microabscesses + granulomatous inflammation granulomatous inflammation extension to extension to veins/nerves. veins/nerves.

Late complication: chronic ulceration of toes or Late complication: chronic ulceration of toes or fingers fingers gangrene. gangrene.

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BUERGER´S DISEASE...(cont.)

CLINICAL FEATURES: CLINICAL FEATURES:

Claudication in feet and/or hands sometimes Claudication in feet and/or hands sometimes centrally radiated. centrally radiated.

Numbness and tingling in limbs + Raynaud´s Numbness and tingling in limbs + Raynaud´s phenomenon. phenomenon.

Skin ulcerations + gangrene of digitsSkin ulcerations + gangrene of digits

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TUMORS OF BLOOD VESSELS

Cavernous hemangioma

•Large blood filled vascular spaces•Separated by mild to moderate amount of CT stroma•Intravascular thrombosis may be seen.

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Kaposi sarcoma

Coalescent red-purple macules and plaques of the skin

sheets of plump, proliferating spindle cells