Pathology of Non-Atherosclerotic Vascular Disease

Question 1

What is Monckeberg disease? When is it seen?

Answer 1

Calcific medial sclerosis

• > a type of calcification of the media of medium-sized muscular arteries (arteriosclerosis)
• > seen as incidental finding of X-ray or mammogram

Question 2

What is a true vs false aneurysm?

Answer 2

True - dilatation of entire wall of cardiovascular system

False - more like a hematoma, communicates with vascular lumen but has ripped through and is walled off by adjacent connective tissue

Question 3

What type of aneurysm is a berry aneurysm?

Answer 3

Saccular aneurysm - focal, spherical outpouching

Question 4

What is it called when an aneurysm is large and linearly dilates along the entire circumference of the vessel?

Answer 4

Fusiform aneurysm

Question 5

What things can cause aneurysm? Include what a mycotic aneurysm is.

Answer 5

Significant weakening of vascular wall

• > atherosclerosis is most common
• > cystic medial degeneration
• > congenital abnormalities (i.e. berry aneurysms in ADPKD)
• > Vasculitides
• > Mycotic aneurysm - aneurysm due to infective embolus

Question 6

Who usually gets an abdominal aortic aneurysm, and what is the typical etiology? What type of aneurysm is it?

Answer 6

Men with a genetic predisposition

Etiology - atherosclerosis since there is little vasa vasorum in abdominal aorta -> thinning and destruction of media
-> Fusiform aneurysm

Question 7

What are the complications of abdominal aortic aneurysm?

Answer 7

1. Rupture - proportional to size
2. Vascular occlusion - due to aneurysm itself or mural thrombosis caused by turbulent flow
3. Embolism - atheromatous or thrombotic debris
4. Compression of neighboring structures - i.e. vertebral bodies

Question 8

What is the pathogenesis of Syphilitic aneurysm and where does it occur?

Answer 8

It is an obliterative endarteritis of tertiary syphilis due to destruction of vasa vasorum in the adventitia -> ischemic damage of the media

Occurs in thoracic aorta, where vasa vasorum is more important

Question 9

How will syphilitic aneurysm appear grossly?

Answer 9

Grossly - fusiform dilatation of aortic arch / thoracic aorta with white, folded appearance on inside, due to contracture of fibrosis “tree-barking”**

Question 10

How will syphilitic aneurysm appear microscopically?

Answer 10

Intima - undamaged, will have ribbon-like effect w/alternating bulges into lumen

Media - scattered patches of smooth muscle cell loss with inflammation & subsequent fibrosis (ischemia)

Adventitia - Vasa vasorum surrounding by plasma cells and lymphocytes -> destruction via syphilis

Question 11

What are the possible complications of syphilitic aneurysm? What is notably absent?

Answer 11

1. Aortic insufficiency - aneurysm increases aortic annulus size -> regurgitation and LV volume overload
2. Superimposed atherosclerosis / ischemic heart disease - from tubulence
3. Compression / erosion of adjacent structures (absent = bronchi, esophagus, recurrent laryngeal nerves, vertebrae)

Absent = Rupture -> media / adventitia is scarred so rupture is unlikely

Question 12

What is the most common, and two uncommon causes of aortic dissection?

Answer 12

Most common - hypertension

Uncommon - inherited connective tissue disorder (i.e. Marfan), or peripartum (due to volume shifts in pregnancy)

Question 13

Where does aortic dissection occur within the wall, and what are the two types?

Answer 13

A tear in the intima allows blood to enter media. Blood begins dissecting between inner 2/3 and outer 1/3 of media

Type A: proximal dissection - involves ascending aorta +/- descending

Type B: distal dissection - involves descending aorta only

Question 14

What is a double-barreled aorta?

Answer 14

When the aorta dissects both proximally and distally, leading to channel of blood flowing through both the aorta and the aortic dissection

Question 15

What is seen microscopically in the elastic media of aortic dissection?

Answer 15

“cystic” medial degeneration -> loss of layers of elastic connective tissue which are replaced by loose, pale, amorphous extracellular matrix

Question 16

What are the major symptoms of aortic dissection?

Answer 16

Severe chest pain radiating to the back and extending downward

Question 17

What are the complications of aortic dissection and why?

Answer 17

1. Rupture into body cavity -> most often pericardial sac if proximal dissection, leading to tamponade
2. Aortic insufficiency - valve becomes flopping when unanchored from wall
3. External compression of aortic branches (i.e. renal)

Question 18

What is the most common result of infectious vasculitis?

Answer 18

Mycotic aneurysm -> usually due to bacterial or fungal pathogen (i.e. aspergillus)

Question 19

What are the two types of antineutrophil cytoplasmic antibodies (ANCAs) and their targets?

Answer 19

cytoplasmic, c-ANCA - proteinase-3

perinuclear, p-ANCA - myeloperoxidase

p doesn’t go with p

Question 20

What are the three types of immune-mediated, noninfectious vasculitis?

Answer 20

1. Immune-complex mediated
2. ANCA-mediated
3. Anti-endothelial antibody mediated

Question 21

How are ANCAs originally generated and what is their pathogenesis?

Answer 21

Initial insult -> neutrophil activation -> sensitization of immune system against neutrophil antigens PR3 and MPO -> antibodies bind neutrophils and cause degranulation + vascular injury

Question 22

What are the three broad possible outcomes of vascular inflammation and injury which can lead to a wide variety of sequellae in vasculitis?

Answer 22

1. Luminal narrowing -> ischemia
2. Thrombosis -> embolic events
3. Aneurysm -> wall weakening and risk or rupture

Question 23

What vessels are involved in temporal arteritis, and what type of inflammation dominates?

Answer 23

Temporal and ophthalmic arteries

Inflammation: Granulomatous inflammation with giant cells lined up on internal elastic lamina, with focal destruction and fibrosis of vessel -> narrowed lumen + ischemia

Question 24

How tends to get temporal arteritis, and what are the symptoms? Should it be treated?

Answer 24

Older adults, present with constitutional symptoms as well as painful and nodular temporal artery, with headache and visual impairment

YES - it needs to be treated very rapidly with systemic corticosteroids if suspected before bilateral vision loss occurs

Question 25

What disease is associated with temporal arteritis and what are its symptoms?

Answer 25

Polymyalgia rheumatica
-Chronic inflammatory condition characterized by joint / muscle pain and stiffness

• > hips and shoulders most affected, with worse symptoms in morning (rheumatica = like rheumatoid arthritis)
• > synovitis of proximal joints / structures

Question 26

What is Takayasu arteritis also called and why? What vessels does it involve?

Answer 26

Pulseless disease - involves aortic arch and its major branches

Associated with weak upper extremity pulses due to degeneration of aortic arch branches

Question 27

What is the vascular pathology of pulseless disease?

Answer 27

Granulomatous inflammation very similar to temporal arteritis, except it involves aorta + branches so giant cells will span the entire thickness of the vessel wall, with luminal narrowing

Question 28

Who does Takayasu arteritis typically affect and what are the symptoms?

Answer 28

Young women - symptoms include neurologic / visual deficits from poor perfusion and strokes / TIAs from thromboembolism.

Can cause myocardial ischemia due to coronary artery involvement or hypertension if it affects kidneys (increased RAA system)

Question 29

What is granulomatosis with polyangiitis also called, and what is the clinical triad?

Answer 29

Wegener’s granulomatosis

Triad:
1. Necrotizing granulomatous inflammation of upper / lower respiratory tract

2. Necrotizing granulomatous vasculitis of small vessels of upper / lower respiratory tract
3. Necrotizing, proliferative glomerulonephritis -> hematuria / proteinuria

Question 30

Who is Wegener’s typically found in, and what marker correlates with disease activity?

Answer 30

Typically middle-aged men

c-ANCA levels (Proteinase-3) correlate with disease activity

Question 31

What vessels are involved in polyarteritis nodosa? Treatment?

Answer 31

Small to medium-sized arteries of kidneys, GI tract, and heart

Notably - LUNGS are spared

Treatment = immunosuppressive therapy - cyclophosphamide + corticosteroids

Question 32

What does polyarteritis nodosa look like under the microscope?

Answer 32

Type III hypersensitivity - patchy, transmural acute / chronic inflammation and fibrinoid necrosis / thrombosis.

Notable: alternating regions of fibrosis and necrosis (lesions of varying stages present)

Question 33

Who typically gets polyarteritis nodosa and what symptoms do they present with?

Answer 33

Young adults - especially following hepatitis B infection

Symptoms - constitutional symptoms, signs of multifocal vascular injury -> hypertension (kidneys), abdominal pain w/melena, skin lesions (nodules)

Question 34

What is Kawasaki disease? What disease is it similar to under the microscope? Who tends to get it?

Answer 34

Mucocutaneous lymph node syndrome

Similar to polyarteritis nodosa, young children tend to get it.

Question 35

What vessels are affected in Kawasaki disease, and what are the clinical symptoms?

Answer 35

Vessels affected are coronary arteries

Symptoms: Erythematous rash of palms / soles (mucosa), peripheral edema (lymph involvement), cervical adenopathy (lymph node syndrome), and cardiovascular complications

Question 36

What are the cardiovascular complications of Kawasaki disease and what is the treatment?

Answer 36

Myocardial infarction or coronary artery aneurysms with possible rupture

Treatment - Aspirin and IV immunoglobulin (aspirin normally contraindicated in children)

Question 37

What vessels does microscopic polyangiitis affect, and what marker correlates with severity?

Answer 37

Smallest vessels, multi-organ involvement, includes arterioles, capillaries, and venules

p-ANCA correlates -> microscopic Polyangiitis

Question 38

What vascular pathology predominates microscopic polyangiitis?

Answer 38

Looks alot like polyarteritis nodosa, except the lesions will be the same age, smaller vessels are affected, and there will be the presence of fragmented neutrophils due to anti-p-ANCA

(also called leukocytoclastic vasculitis. Leukocytoclastic = destruction of WBCs)

Question 39

When does microscopic polyangiitis typically develop and what does it look like clinically?

Answer 39

Frequently following a drug exposure or malignancy

Involves small vessels of kidney, lung, and skin the most:
Palpable purpura on skin, hematuria, and hemoptysis

Question 40

What vasculitis is caused by deposition of IgA immune complexes, especially following an upper respiratory infection in children? What vessels does it preferentially involve?

Answer 40

Henoch-Schonlein purpura
= skin + GI + IgA nephropathy + kids

• > small blood vessels, especially skin and GI tract
• > glomeruli - mesangial deposits of IgA immune complexes, similar to IgA nephropathy

Question 41

What are the symptoms of HSP?

Answer 41

Palpable purpura on buttocks, dorsal legs, and arms

Arthralgias / abdominal pain / intestinal bleeding / renal abnormalities (hematuria, proteinuria, HTN)

Question 42

What is thromboangiitis obliterans also called and what vessels are affected?

Answer 42

Buerger disease

-> small to medium-sized arterties of distal extremities

Question 43

What is the clinical presentation of Buerger disease and how is it treated?

Answer 43

Occurs in young adult smokers

Thrombosis and microabscesses in distal exremities, can include veins and nerves, very PAINFUL and may lead to autoamputation

-> treated with smoking cessation

Question 44

What is Churg-Strauss syndrome and what marker might is be associated with? What disease is associated?

Answer 44

Allergic granulomatous angiitis

• > vasculitis with eosinophil predominance
• > heavily associated with asthma

Question 45

Is Churg-Strauss syndrome focal or widespread? What do lesions look like?

Answer 45

In its most severe phase, it is very widespread, affecting almost any small vessels in any tissue in the body

Lesions are necrotizing granulomatous inflammation with eosinophils

Question 46

What causes varicose veins and what are the most common sites?

Answer 46

Long-standing increased intravenous pressure with poor wall support -> dilated veins with wall abnormalities

Sites:

1. Superficial on lower extremities
2. Submucosal veins - i.e. distal esophagus / rectum due to portal HTN

Question 47

What are the potential complications of varicose veins?

Answer 47

Usually just thrombosis (NOT thromboembolism) and worsening congestion / edema

Submucosal varicosities may hemorrhage

Question 48

What are thrombophlebitis and phlebothrombosis and what usually causes them? Major complication?

Answer 48

Deep vein thrombosis

Usually caused by stasis, occurring in lower extremities

Complication: Pulmonary thromboembolism

Question 49

What typically causes lymphangitis / lymphadenitis?

Answer 49

Bacterial infection spreading thru lymphatic vessels with acute inflammation til it reaches lymph nodes

Question 50

What causes lymphedema?

Answer 50

Obstruction of lymphatic vessels (i.e. filariasis) or s/p surgery / radiation (i.e. breast cancer removal of axillary nodes)

Question 51

What are nevus simplex and port wine stains examples of?

Answer 51

Nevus simplex = salmon patch on skin

Port wine stain - large collection of ruby capillaries

Examples of capillary malformations, the most common type of simple vascular malformation

Question 52

Are nervus simplexes and port wine stains flat or raised? What are they made of?

Answer 52

Flat - patches of discoloration (pink to reddish-purple macules)

Consist of dilated capillaries and/or postcapillary venules

Question 53

Do vascular malformations usually regress? What types of lesions do these include?

Answer 53

No

Includes capillary malformations and lymphatic malformations

Question 54

What would a cystic hygroma be called now and what is it?

Answer 54

Macrocystic lymphatic malformation

Lesion composed of variably-sized, dilated lymphatic channels

Tend to develop under skin of neck / axillary region, may also be microcystic or mixed

Question 55

What is the most common type of benign vascular tumor? What does it look like under the microscope?

Answer 55

Infantile hemangioma - most common tumor of infancy

Looks like plump endothelial cells (with unique markers and pericytes) that form densely packed vascular spaces

Question 56

When do infantile hemangiomas appear and do they regress? Where do they appear?

Answer 56

Tend to be in subcutaneous skin / face, appearing within first few weeks of life

Gradually regress over 5-9 years

Question 57

How does a congenital hemangioma differ from an infantile hemangioma, and do they regress?

Answer 57

Congenital must be present at birth, and may involve other locations like soft tissue / viscera. May also involve lympatic vessels / larger, dilated vessels.

Wide variability in regression -> some regress rapidly, others never do

Question 58

What causes Kaposi sarcoma and where do they tend to appear?

Answer 58

STI with HHV-8 in combination with immunosuppression

Appear in reddish-purple plaques on skin (esp. nose), mucous membranes, lymph nodes, and visceral organs (esp. GI tract)

Question 59

What does Kaposi sarcoma look like under the microscope?

Answer 59

Irregular vascular spaces, plump spindle cells, and mononuclear infiltrate (chronic inflammation to fight virus) with hemorrhage

Question 60

What is the classic form of Kaposi sarcoma and where does it tend to be?

Answer 60

Indolent form affecting distal extremities of lower limb preferentially of Eastern European (Russia) / Mediterranean men

Question 61

What are the features of endemic Kaposi sarcoma?

Answer 61

Aggressive -> found in Africa, primarily involves lymph nodes

Question 62

What are the features of immunosuppression-associated Kaposi sarcoma?

Answer 62

In AIDS / transplant patients

Multi-organ systemic disease with visceral involvement
-> treat with immunosupportive therapy + antineoplastics

Question 63

What are the common sites for angiosarcoma and what is it?

Answer 63

Highly aggressive malignancy of endothelial cells

Common sites include skin, breast, and liver

Question 64

What carcinogens is angiosarcoma associated with?

Answer 64

polyvinyl chloride (PVC), Thorotrast (radiocontrast agent), arsenic (pesticides)