vascular pathology

Question 1

normal vessels (not on test)

Answer 1

Intima - single layer of endothelial cells attached to basement membrane; demarcated from media by internal elastic lamina

Media of elastic arteries (e.g., aorta) arranged in layers of lamellar units of elastin fibers and smooth muscle cells like tree rings- high elastin content allows vessels to expand during systole and recoil during
In muscular arteries, media is mostly made of circumferentially oriented smooth muscle cells

Adventitia lies external to media; consists of loose connective tissue and nerve fibers; in many arteries separated from media by a well-defined external elastic lamina

Question 2

arteries divided based on size and structure

Answer 2

(1) large or elastic arteries including the aorta, the major branches of the aorta, and pulmonary arteries

(2) medium-sized or muscular arteries comprising smaller branches of the aorta (e.g., coronary and renal arteries)

(3) small arteries (≤2 mm in diameter) and arterioles (20 to 100 µm in diameter) within tissues and organs

Question 3

capillaries (not on test)

Answer 3

-slightly smaller (5 µm) than diameter of a red blood cell; have endothelial cell lining but no media
-Collectively, have a huge cross-sectional area and also relatively low flow rate
-Thin walls and slow flow allows for exchange of diffusible substances between blood and tissues

-Blood from capillary beds flows into postcapillary venules and then sequentially through collecting venules and small, medium, and large veins

-Relative to arteries, veins have larger diameters, larger lumens, are thinner with less well-organized walls

-Lymphatics are thin-walled, endothelium-lined channels that drain lymph (water, electrolytes, glucose, fat, proteins, and inflammatory cells) from the interstitium of tissues, eventually reconnecting with the blood stream via the thoracic duct

Question 4

Arteriovenous fistulas aka ArterioVenous Malformation (AVM)

Answer 4

-abnormal direct connections between arteries (high pressure) and veins (low pressure) that bypass capillaries
-MC- developmental defects
-Can rupture

Question 5

arteriosclerosis

Answer 5

-“hardening of the arteries”

-affects small arteries and arterioles and may cause downstream ischemic injury
-Mönckeberg medial sclerosis: usually not clinically significant.
-Fibromuscular intimal hyperplasia occurs in muscular arteries larger than arterioles; associated with stents or balloon angioplasty)

Question 6

atheroma (plaque)

Answer 6

-RAISED FOCAL LESION STARTING WITHIN THE INTIMA
-SOFT, YELLOW CORE OF LIPID (CHOLESTEROL AND CHOLESTEROL ESTERS), COVERED BY FIBROUS CAP

-Three major components:
-1. Cells: smooth muscle, macrophages, leukocytes (T lymphocytes)
-2. ECM: collagen, elastic fibers, proteoglycans
-3. Intracellular and extracellular lipid

Question 7

atherogenesis!!!!

Answer 7

-Current model: response to injury –chronic inflammatory and healing response of the arterial wall initiated by endothelial injury!!!!!!!!!

-IMPORTANT CAUSES OF ENDOTHELIAL INJURY:
Hypercholesterolemia - impairs endothelial cell function by increasing local ROS (reactive oxygen species)
Hemodynamic effects:
-Areas of disturbed, turbulent blood flow - more plaques
-Laminar blood flow protects against AS
-Hypertension directly increases hemodynamic stress on endothelial cells
-Inflammation – triggered by accumulation of cholesterol crystals and free fatty acids in macrophages and other cells

Question 8

atherosclerosis

Answer 8

-Endothelial injury in vivo may also be caused by cigarette smoke, homocysteine, viruses and bacteria ? (CMV and C.pneumoniae studies – circumstantial evidence)

-Hyperhomocysteinemia – increased serum homocysteine levels correlate with coronary atherosclerosis, PVD, stroke, venous thrombosis

Question 9

response to injury hypothesis: chronic endothelial injury

Answer 9

-hyperlipidemia
-hypertension
-smoking
-homocysteine
-hemodynamic factors
-toxins
-viruses
-immune reactions

Question 10

pathogenesis: overview of progression

Answer 10

-Endothelial injury: endothelial dysfunction causes increased permeability, wbc adhesion, and exposure to thrombogenic agents (thrombosis)
-Accumulation of lipoproteins (mostly LDL), in vessel wall; lipoproteins undergo oxidation; intracellular and extracellular accumulation of lipids
-Monocytes (mostly) adhere to endothelium, migrate into intima and transform into macrophages/foam cells; platelets also adhere to endothelium
-Factors (e.g., PDGF, FGR) released from activated platelets, macrophages, and vascular cells cause smooth muscle cells to migrate from media to intima
-Smooth muscle cells proliferate in intima and produce ECM so that collagen and proteoglycans accumulate and plaque mature
-Lipid accumulation – extracellulary and within macrophages and smooth muscle cells
-Calcification of ECM and necrotic debris late in pathogenesis

Question 11

hypercholesteremia in plaque formation

Answer 11

-LDL is mostly cholesterol
-Chronic hypercholesteremia may cause endothelial dysfunction by producing oxygen free radicals
-Lipoproteins accumulate within intima
-LDL in macrophages oxidized by free radical generation, then engulfed by macrophages via the scavenger receptor

Question 12

inflammatory cells in AS (dont need all details)

Answer 12

-Inflammation triggered by accumulation of cholesterol crystals and free fatty acids in macrophages

-Dysfunctional endothelial cells express surface selective adhesion molecules, VCAM-1 – binds monocytes and T lymphocytes

-Monocytes adhere to endothelium, migrate to intima, and transform to macrophages that engulf oxidized LDL

-Progressive accumulation of lipids

-Macrophages produce IL-1,TNF and chemokines further increasing adhesion of wbcs

-T-lymphs and monocytes also interact with cytokines and a chronic inflammatory state develops

Question 13

maturation/stabilization of plaque

Answer 13

-Smooth muscle cells migrate from media to intima, proliferate, and elaborate ECM components

-Growth factors such as PDGF, FGF, and TGF contribute to smooth muscle cell proliferation

-Smooth muscle cells in vessel wall make extracellular matrix molecules (esp. collagen) which stabilize plaques

Question 14

what can happen?

Answer 14

-Rupture, ulceration, erosion (exposes blood stream to highly thrombogenic substances) leading to thrombosis and possible complete occlusion
-Hemorrhage into plaque; may extend plaque or induce rupture
-Atheroembolism
-Aneurysm formation leads to wall weakness

Question 15

atherosclerosis progression (dont need to know all diff types)

Answer 15

-Type I – isolated macrophage foam cells!!
-Type II – intracellular lipid accumulation
-Type III - Type II + small extracellular lipid pools
-Type IV – Type II + core of extracellular lipid
-Type V – lipid core and fibrotic layer, or multiple lipid cores, fibrotic/calcific layer
-Type VI – surface defect; hematoma/ hemorrhage/thrombosis

-fatty steaks are earliest lesions seen

Question 16

non atherosclerosis vascular diseases

Answer 16

-hypertension
-aneurysms
-vasculitides
-vein disorders
-neoplasms

Question 17

hypertension

Answer 17

-HYPERTENSION causes ATHEROSCLEROSIS: Pressure causes intimal damage.
-ATHEROSCLEROSIS causes HYPERTENSION. Reduction of lumen sizes increases pressure.
-“ESSENTIAL” 95%
-“SECONDARY” 5%

Question 18

secondary HTN (dont need to know)

Answer 18

-Renal  
-Acute glomerulonephritis    
-Chronic renal disease    
-Polycystic disease    
-Renal artery stenosis    
-Renal artery fibromuscular dysplasia
-Renal vasculitis    
-Renin-producing tumors    

-Endocrine  
-Adrenocortical hyperfunction
(Cushing syndrome, primary aldosteronism, congenital adrenal hyperplasia, licorice ingestion)
-Exogenous hormones (glucocorticoids, estrogen [including pregnancy-induced and oral contraceptives], sympathomimetics and tyramine-containing foods, monoamine oxidase inhibitors)
-Pheochromocytoma, Acromegaly, Hypothyroidism (myxedema), Hyperthyroidism
-Pregnancy-induced    

-Cardiovascular: Coarctation of aorta, Polyarteritis nodosa (or other vasculitis)
Increased intravascular volume

-MISC: Increased cardiac output, Rigidity of the aorta, Neurologic, Psychogenic, Increased intracranial pressure, Sleep apnea, Acute stress, including, surgery

Question 19

renin -> angiotensin -> Aldosterone axis (RAAS)

Answer 19

-Renin: proteolytic enzyme made by renal juxtaglomerular cells, released in response to
-low blood pressure in afferent arterioles
-elevated levels of circulating catecholamines
-or low sodium levels in the distal convoluted renal tubules
-Renin cleaves plasma angiotensinogen to angiotensin I; converted to angiotensin II by angiotensin-converting enzyme (ACE), mainly from vascular endothelium

-Angiotensin II raises blood pressure by:
-(1) inducing vascular contraction
-(2) stimulating aldosterone secretion by adrenal gland
-(3) increasing tubular sodium resorption

-Adrenal aldosterone increases blood pressure by effect on blood volume; aldosterone increases sodium resorption (and thus water) in distal convoluted tubules, which increases blood volume

Question 20

summary

Answer 20

-Blood pressure is determined by vascular resistance and cardiac output
-Vascular resistance is regulated at the level of the arterioles, influenced by neural and hormonal inputs
-Cardiac output determined by heart rate and stroke volume, strongly influenced by blood volume
-Blood volume regulated mainly by renal sodium excretion or resorption
-Renin, major regulator of blood pressure, secreted by kidneys in response to decreased blood pressure in afferent arterioles
-Renin cleaves angiotensinogen to angiotensin I; subsequent endothelial catabolism produces angiotensin II, which regulates blood pressure by:
-increasing vascular smooth muscle tone
-increasing adrenal aldosterone secretion, which increases renal sodium resorption

Question 21

hypertension vessel pathology

Answer 21

-Hyaline arteriolosclerosis
-Arterioles show homogeneous, pink hyaline thickening with associated luminal narrowing
-Why? both plasma protein leakage across injured endothelial cells and increased smooth muscle cells matrix synthesis in response to chronic hemodynamic pressures of hypertension

-Hyperplastic arteriolosclerosis
-Occurs in severe hypertension; vessels exhibit concentric, laminated (“onion-skin”) thickening of the walls with luminal narrowing
-The laminations consist of smooth muscle cells with thickened, reduplicated basement membrane; in malignant hypertension, accompanied by fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis), especially in the kidney

Question 22

mechanisms: essential hypertension

Answer 22

-Genetic factors
-Insufficient renal sodium excretion may lead to increase in fluid volume, increased cardiac output, and peripheral vasoconstriction, causing elevated blood pressure
-Vasoconstrictive influences: factors that induce vasoconstriction or stimuli that cause structural changes in vessel wall, can lead to an increase in peripheral resistance
-Environmental factors: stress, obesity, smoking, physical inactivity, and heavy salt consumption

Question 23

aneurysm/dissection

Answer 23

-Localized abnormal dilation of a blood vessel or the heart; may be congenital or acquired
-True aneurysm: involves all layers of an intact (but attenuated) arterial wall or the thinned ventricular wall of the heart
-False aneurysm (aka pseudoaneurysm): defect in vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space
-Arterial dissection: blood enters a defect in the arterial wall and tunnels through medial or medial-adventitial planes

Question 24

aneurysm pathogenesis

Answer 24

-Occurs when structure or function of connective tissue within vascular wall is compromised

-Defects in synthesis or breakdown of connective tissue contribute to pathobiology of both heritable aneurysmal diseases and common, sporadic forms:

-Poor intrinsic quality of vascular wall connective tissue (e.g., Ehlers-Danlos syndrome - weak vessel walls due to defective type III collagen synthesis)

-Abnormal transforming growth factor-β (TGF-β) signaling: excessive TGF-β activity changes vascular wall remodeling (mostly ascending aorta) which leads to decreased ECM content and integrity with aneurysmal dilation (e.g., Marfan syndrome - defective synthesis of the scaffolding protein fibrillin leads to inability to sequester endogenously produced TGF-β)

-Balance of collagen degradation and synthesis altered by inflammation and associated proteases

-Vascular wall weakened by loss of smooth muscle cells or inappropriate synthesis of noncollagenous or nonelastic ECM. (e.g., ischemia of inner media occurs with atherosclerotic thickening of intima, due to increased distance that oxygen and nutrients must diffuse)

Question 25

abdominal aortic aneurysm

Answer 25

-Aneurysms occurring as a result of atherosclerosis form most commonly in the abdominal aorta and common iliac arteries

-AAAs occur more frequently in men and in smokers, rarely developing before age 50; Atherosclerosis major cause

-Risk of rupture directly related to size of aneurysm (0% for AAAs ≤4 cm in diameter; 1% per year for AAAs between 4 and 5 cm; 11% per year for AAAs between 5 and 6 cm; 25% per year for aneurysms >6 cm.

Question 26

thoracic aneurysms

Answer 26

-Most commonly associated with hypertension
-Before dissection or rupture, symptoms can include:
-(1) chest pain from encroachment or erosion into bone
-(2) myocardial ischemia from compression of a coronary artery
-(3) difficulty swallowing due to compression of the esophagus
-(4) hoarseness from irritation of or pressure on the recurrent laryngeal nerves
-(5) respiratory complications from compression of the bronchi

-Most do not cause symptoms unless they rupture

Question 27

aneurysms (leutic)

Answer 27

-Tertiary syphilis: rare cause of aortic aneurysms in which obliterative endarteritis occurs in vasa vasorum of the thoracic aorta leading to medial ischemia: results in SMC loss, elastic fiber loss, and inadequate/inappropriate ECM synthesis
-Mostly thoracic
-PLASMA CELLS predominate

Question 28

aneurysms (sequelae)

Answer 28

-RUPTURE
-OBSTRUCTION
-EMBOLISM

-COMPRESSION
-URETER
-SPINE

-MASS EFFECT

Question 29

aortic dissection

Answer 29

-Occurs when blood separates laminar planes of media and forms blood-filled channel within aortic wall; can rupture through adventitia and hemorrhages into adjacent spaces
-Pathogenesis: Hypertension major risk factor
-Aortas of hypertensive patients have medial degenerative changes with smooth muscle cell loss and altered ECM content
-Other dissections occur in inherited or acquired connective tissue disorders with defective TGF-β signaling or defective ECM synthesis or degradation
-Ultimate trigger for intimal tear and initial intramural aortic hemorrhage usually not known

-Usually starts with an intimal tear!!!! – for most spontaneous dissections, tear occurs in the ascending aorta, usually within 10 cm of the aortic valve
-Dissection can extend retrograde toward heart as well as distally, sometimes as far as the iliac and femoral arteries

-After intimal tear, blood flow under systemic pressure dissects through media leading to progression of the hematoma
-Usually medial degeneration is present at site of tear showing elastic fiber fragmentation and loss, mucoid ECM accumulation, and SMC attrition; inflammation usually absent

Question 30

dissection

Answer 30

-The dissecting hematoma spreads between lamellar units of the outer third of the media or between media and adventitial layers
-Can rupture through adventitia causing massive hemorrhage (e.g., into the thoracic or abdominal cavities) or cardiac tamponade (hemorrhage into pericardial sac)
-Traumatic chest injury (e.g., motor vehicle accident, or even extremely vigorous cardiopulmonary resuscitation) can cause intimal tears that begin after the origin of arch vessels at the ligamentum arteriosum

Question 31

debakey (not on test)

Answer 31

Type A dissections: more common (and dangerous) proximal lesions involving either both ascending and descending aorta or ascending aorta only (types I and II of the DeBakey classification)

• Type B dissections: Distal lesions not involving the ascending aorta and usually beginning distal to the subclavian artery (called DeBakey type III)

Question 32

vasculitis

Answer 32

-Vessel wall inflammation
-Most vasculitides affect small vessels ranging from arterioles to capillaries to venules
-Some vasculitides affect only vessels of a certain size or location

-AKA Vasculitides:
-TEMPORAL “GIANT CELL” ARTERITIS
-TAKAYASU ARTERITIS
-POLYARTERITIS NODOSA
-KAWASAKI DISEASE
-Granulomatosis with polyangiitis (formerly know as Wegener’s)
-THROMBOANGITIS OBLITERANS (BUERGER[‘s] DISEASE)
-OTHER
-Infectious

Question 33

vasculitides

Answer 33

-Mostly arterial
-Infectious (5%) vs. Non-infectious (95%)
-NON-infectious are generally “AUTO”-IMMUNE

-Persistent findings:
-Immune complexes
-ANTI-NEUTROPHIL AB’s (ANCA) (Granulomatosis with polyangiitis, “Temporal” arteritis)
-ANTI-ENDOTHELIAL CELL AB’s (Kawasaki)

-Often DRUG related (Hypersensitivity, e.g.)

Question 34

temporal arteritis AKA giant cell arteritis

Answer 34

-ADULTS – chronic granulomatous inflammation of large to small sized arteries mostly affecting head; most common form in elderly adults; rare < 50 years
-Temporal artery most easily biopsied (visible, palpable, surgically accessible)
-GRANULOMATOUS WALL inflammation diagnostic

-Pathogenesis – mostly likely result of Tcell-mediated immune response to unknown vessel wall antigen
-Immune etiology supported by granulomatous inflammation, association with certain major histocompatibility complex (MHC) class II haplotypes, and excellent therapeutic response to steroids

-Symptoms may be vague and constitutional—fever, fatigue, weight loss—or may involve facial pain or headache, especially along superficial temporal artery (may be painful to palpation)
-Ocular symptoms (ophthalmic artery) occur abruptly in about 50% of patients ranging from diplopia to complete vision loss
-Diagnosis depends on biopsy and histologic confirmation; negative biopsy does not exclude diagnosis
-Treatment usually corticosteroids or anti-TNF therapies

Question 35

temporal arteritis morphology

Answer 35

-Involved arterial segments develop intimal thickening (occasional thromboses), reduces luminal diameter
-Classic lesions show medial granulomatous inflammation centered on the internal elastic membrane with elastic lamina fragmentation
-Infiltrate of T cells and macrophages

-Multinucleated giant cells seen in approximately 75% of biopsied specimens but granulomas and giant cells can be rare or absent
-Inflammatory lesions only focally distributed along vessel

Question 36

takayasu arteries (dont need to know anything else)

Answer 36

-autoimmune, pulseless disease, no pulses in upper extremities !!!!

Question 37

polyarteritis nodosa (PAN)- dont need details

Answer 37

-Systemic vasculitis of small- or medium-sized muscular arteries, usually affects renal and visceral vessels but NOT pulmonary circulation
-Third of patients have chronic hepatitis B, leading to formation of HBsAg-HbsAb complexes that deposit in affected vessels; cause unknown in most cases
-Segmental transmural necrotizing inflammation of small- to medium-sized arteries; kidney, heart, liver, and GI tract vessels involved (descending order); results in ulcerations, infarcts, ischemic atrophy, or hemorrhage distal to lesions

-Acute phase: transmural inflammation of arterial wall with mixed inflammation (neutrophils, eosinophils, mononuclear cells) often with fibrinoid necrosis and luminal thrombosis
-Clinical Features – result from ischemia and infarction of affected tissues/organs; All age groups but mostly young adults; remitting and episodic course, with long symptom-free intervals
-Typical presentation: combination of rapidly accelerating hypertension (renal artery involvement); abdominal pain and bloody stools; diffuse myalgias; and peripheral neuritis
-Renal involvement - major cause of mortality; if untreated, typically fatal, immunosuppression can result in remissions or cure in 90% of cases

Question 38

kawasaki disease (all you need to know !)

Answer 38

-!Acute, febrile, usually self-limited illness: infancy and childhood associated with large- to medium-sized vessel arteritis (80% < 4 years of age).
-!Involvement of coronary arteries (coronary arteritis) can result in aneurysms that rupture or thrombose, causing myocardial infarction

Question 39

granulomatosis with polyangiitis

Answer 39

-Formerly known as Wegener’s granulomatosis
-respiratory and renal
-Necrotizing vasculitis with triad:
-Acute necrotizing granulomas of upper respiratory tract (ear, nose, sinuses, throat) or ower respiratory tract (lung) or both
-Necrotizing or granulomatous vasculitis affecting small- to medium-sized vessels mostly in lungs and upper airways but other sites also
-Focal necrotizing, often crescentic, glomerulonephritis (micro)

-Most likely a form of T cell–mediated hypersensitivity response to normally “innocuous” inhaled microbial or other environmental agents
-PR3-ANCAs present in up to 95% of cases
-Upper respiratory tract lesions range from inflammatory sinusitis with mucosal granulomas to ulcerative lesions of nose, palate, or pharynx, rimmed by granulomas with geographic patterns of central necrosis and accompanying vasculitis
-Renal lesions range from mild, focal glomerular necrosis to more advanced glomerular lesions with diffuse necrosis and crescent formation (crescentic glomerulonephritis)

Question 40

granulomatosis with polyangiitis- GPA

Answer 40

-M > F; average age 40 years

-Classic presentation: bilateral pneumonitis with nodules and cavitary lesions (95%), chronic sinusitis (90%), mucosal ulcerations of nasopharynx (75%), and renal disease (80%); rashes, myalgias, joint involvement, neuritis, and fever can occur

-Rapidly fatal if untreated (80% mortality within 1 year); treatment with steroids, cyclophosphamide, TNF antagonists, and anti–B-cell antibodies result in chronic relapsing and remitting disease

Question 41

thromboangiitis obliterans beurger disease

Answer 41

-Segmental, thrombosing, acute and chronic inflammation of medium- and small-sized arteries, especially tibial and radial arteries
-Almost exclusively in heavy cigarette smokers, usually before the age of 35 (young!)
-Pathogenesis - either direct EC toxicity caused by some tobacco component or immune response to same agents
-Acute and chronic inflammation with luminal thrombosis; Inflammation extends into contiguous veins and nerves (rare with other vasculitides)
-Early manifestations: Raynaud phenomenon (see later), instep foot pain induced by exercise (instep claudication), and superficial nodular phlebitis (venous inflammation)
-Severe pain—even at rest— due to neural involvement
-Chronic extremity ulcerations can develop, progressing over time to gangrene
-Early in disease, smoking cessation often improves disease; but once established does not help

Question 42

raynaud phenomenon

Answer 42

-Results from exaggerated vasoconstriction of arteries and arterioles in responses to cold or emotion
-Most commonly affects extremities, especially fingers and toes, sometime also nose, earlobes, or lips
-Restricted blood flow causes paroxysmal pallor and cyanosis, if severe; involved digits classically show “red, white, and blue” color changes (proximal vasodilation, central vasoconstriction, and more distal cyanosis)

-Primary Raynaud phenomenon affects 3% to 5% of general population, most often young women, usually symmetrically involves extremities, usually does not progress - results from intrinsic hyperreactivity of medial SMCs
-Secondary Raynaud phenomenon - vascular insufficiency due to arterial disease caused by other conditions (e.g., including SLE, scleroderma, Buerger disease, or atherosclerosis); usuall asymmetric involvement of extremities; worsens over time

Question 43

varicose veins

Answer 43

-Abnormally dilated, tortuous veins produced by prolonged, increased intraluminal pressure with vessel dilation and incompetence of venous valves
-Superficial veins of upper and lower leg commonly involved
-Obesity increases risk
-Incompetence of venous valves leads to stasis, congestion, edema, pain, and thrombosis
-Secondary tissue ischemia results from chronic venous congestion and poor vessel drainage leading to stasis dermatitis (from hemolysis of extravasated red cells) and ulcerations

Question 44

thrombophlebitis and phlebothrombosis

Answer 44

-Venous thrombosis and inflammation usually in deep leg veins but also the periprostatic venous plexus and the pelvic venous plexus in females, large veins in skull and the dural sinuses (especially with infection or inflammation)
-Decreased blood flow due to prolonged immobilization - most common cause of lower extremity deep venous thrombosis (DVT) (extended bed rest or sitting during long airplane or automobile trips, post-op, CHF, pregnancy, oral contraceptive use, malignancy, and obesity)
-In cancer, especially adenocarcinomas, hypercoagulability because of tumor elaboration of procoagulant factors – usually venous thromboses appear in one location, disappear, and then occur in another site— migratory thrombophlebitis (Trousseau syndrome)
-Thrombi in legs usually asymptomatic (sometimes, pain can be produced by pressure over affected veins, squeezing calf muscles, or forced dorsiflexion of foot (Homan sign)) ; absence of these findings does not exclude diagnosis of DVT

Question 45

lymphedema

Answer 45

-From blockage of previously normal lymphatics, including:
-Tumors obstructing lymphatic channels or regional lymph nodes
-Surgical procedures that sever lymphatic connections (e.g., axillary lymph node resection in a radical mastectomy)
-Postradiation fibrosis
-Filariasis (worm)
-Postinflammatory thrombosis and scarring

-Increased hydrostatic pressure in lymphatics distal to obstruction causes edema

Question 46

vascular tumors

Answer 46

-BENIGN (Do not metastasize) – rare mitoses
-INTERMEDIATE (rarely metastasize)
-MALIGNANT (FREQUENT and EARLY metastases, especially to lung) – many mitoses, severe atypia of cells

Question 47

hemangioma

Answer 47

-Common tumors composed of blood-filled vessels
-Most present from birth, initially increase in size, many eventually regress spontaneously

-Capillary hemangiomas - most common type; occur in skin, subcutaneous tissues, and mucous membranes of oral cavities and lips; also in liver, spleen, and kidneys
-Juvenile hemangiomas (strawberry-type hemangiomas) of newborn skin - extremely common (1 in 200 births), can be multiple; grow rapidly for a few months, but fade by 1 to 3 and regress by age 7 in most cases
-Cavernous hemangiomas – made of large, dilated vascular channels; more infiltrative, frequently involve deep structures, do not spontaneously regress;

Question 48

lympgangioma

Answer 48

-Benign lymphatic counterparts of hemangiomas.
-Simple (capillary) lymphangiomas - slightly elevated, sometimes pedunculated lesions up to 1 to 2 cm in diameter; mostly in head, neck, and axillary subcutaneous tissue
-Cavernous lymphangiomas (cystic hygromas) - typically in neck or axilla of children; can be extremely large
-cavernous lymphangiomas of the neck common in Turner syndrome

Question 49

glomus tumor glomangioma

Answer 49

-benign, very painful tumors arising from modified SMCs of glomus bodies (arteriovenous structures involved in thermoregulation)
-May superficially resemble hemangiomas; however, glomangiomas arise from SMCs rather than ECs
-Most commonly found in distal portion of the digits, especially under fingernails
-Excision curative

Question 50

intermediate-grade (boderline) tumors: kaposi sarcoma

Answer 50

-Vascular neoplasm caused by human herpesvirus 8 (HHV8, aka Kaposi sarcoma herpesvirus
-between benign and malignant
-Classic KS - older men of Mediterranean, Middle Eastern, or Eastern European descent; can be associated with malignancy or altered immunity, but not HIV infection - multiple red-purple skin plaques or nodules, usually in lower legs; usually persistent, asymptomatic, remain localized to skin and subcutaneous tissue
-Endemic African KS - HIV-seronegative individuals younger than age 40 years; can follow indolent or aggressive course
-Transplant-associated KS occurs in solid-organ transplant recipients receiving T-cell immunosuppression; usually aggressive
-AIDS-associated (epidemic) KS - AIDS-defining illness; worldwide, most common HIV-related malignancy; often disseminates widely early in its course

-Pathogenesis - infection by HHV8, transmitted sexually and potentially via oral secretions and cutaneous exposures; virus causes lytic and latent infections in ECs

-In classic KS skin lesions progress through three stages:
-Patches are red-purple
-With time, lesions become larger, violaceous, raised plaques
-Eventually, lesions become nodular (micro: sheets of plump, proliferating spindle cells, mostly in the dermis or subcutaneous tissue with small vessels and slitlike spaces with red cells, mitoses increased

Question 51

angiosarcoma

Answer 51

-Malignant endothelial neoplasms
-Older adults more commonly affected
-Occur most often in skin, soft tissue, breast, and liver
-Can also arise in setting of lymphedema, classically in ipsilateral upper extremity several years after radical mastectomy for breast cancer
-Hepatic angiosarcomas: associated with various carcinogenic exposures including arsenic (e.g., in pesticides), Thorotrast (radioactive contrast agent formerly used for radiologic imaging), and polyvinyl chloride
-Locally invasive, can readily metastasize; 5-year survival rates approximately 30%