Chapter 11: Veins/Lymph, DVT, Vascular Tumors Flashcards
Which 3 types of vessels are most often affected by vasculitis?
- Arterioles
- Capillaries
- Venules
Why is distinguishing between infectious and immune-mediated causes of vasculitis important as far as tx goes?
- Immune-mediated can be treated w/ immunosuppressive therapy
- This tx would be counter-productive for infectious causes
How can a non-infectious vasculitis be indirectly triggered by an infection?
Generation of immune complexes or triggering cross-reactive immune response
Infectious causes of vasculitis do so through ________ invasion
Direct
Which non-infectious vasculitis is the only one to affect the aorta amongst other vessels?
Giant Cell (Temporal) Arteritis
Which lesions are most common for Drug Hypersensitivity Vasculitis?
Skin lesions
Immune complex-associated vasculitis may be seen in which systemic immunologic disorder?
SLE
A pt >40 yo with history ± polymyalgia rheumatica is most likely to have what type of vasculitis?
Giant Cell (Temporal) Arteritis
Immune complex vasculitis is due to the production of what?
What deposits in the vascular walls?
- Production of autoantibodies and formation of immune complexes
- Deposition of antigen-antibody complexes in vascular walls
Why is it important to consider Drug Hypersensitivity as a cause of vasculitis as far as treatment goes?
Stop drug –> resolution of vasculitis!
What are very useful diagnostic markers of non-infectious vasculitis and their titers mirror clinical severity?
ANCAs
MPO-ANCA’s are found in what 2 types of non-infectious vasculitis?
- Microscopic polyangiitis
- Churg-Strauss syndrome
ANCAs can directly activate which immune cells and cause the release of?
Neutrophils, stimulating release of ROS and proteolytic enzymes
Why are ANCA-associated vasculitides often described as “pauci-immune”?
ANCA Ab directed against cellular constituents and do NOT form circulating immune complexes
Giant cell arteritis stems from an immune response by which cells and causes inflammation of arteries where?
- T cell mediated (CD4+ > CD8+)
- Inflammation of arteries in the head, especially temporal a.
Which 2 types of antibodies are seen in 2/3 of pt’s with Giant Cell (temporal) Arteritis?
anti-endothelial cell and anti-SM cell
What do the classic lesions associated with Giant Cell (Temporal) Arteritis exhibit morphologically?
- Granulomatous inflammation w/ multinucleated giant cells
- Fragmentation of the elastic lamina and intimal thickening
What are the common signs/sx’s of Giant Cell (Temporal) Arteritis?
- Facial pain or HA, most intense along course of superficial temporal a.; painful to palpation***
- Diplopia or complete vision loss
Why is biopsy of at least a 1-cm segment required for diagnosis of Giant Cell (Temporal) Arteritis?
As it can be extremely PATCHY and FOCAL
Treatment for Giant Cell (Temporal) Arteritis?
Corticosteroidsoranti-TNF therapies
Granulomatous vasculitis of medium and large arteries characterized by ocular disturbances and marked weaking of the pulses and low BP in the UE’s is characteristic of?
Takayasu Arteritis (aka pulseless disease)
Takayasu arteritis has similar histological findings as those seen in giant cell arteritis, except involves which vessels?
Aortic arch (aortitis) and major branch vessels
Since many features of Takayasu arteritis are shared with Giant Cell arteritis, the distinction between the 2 is primarily made how?
- AGE of the pt
- Takayasu = younger (<50 yo)
- Giant cell = older (>50 yo)
Which vessels are the major ones affected in Takayasu Arteritis?
- Aortic arch and major branch vessels
- Pulmonary a. (1/2 of cases)
- Coronary and renal arteries
Major signs/sx’s associated with Takayasu Arteritis?
Sx’s associated w/ involvement of renal, pulmonary, and distal aorta?
- Reduced BP and pulses in carotids and UE’s
- Ocular disturbances + Neuro deficits
- If distal aorta involved –> claudication of legs
- Pulmonary a. involvement –> pulmonary HTN
- Renal a. involvement –> systemic HTN
In 1/3 of pt’s with polyarteritis nodosa the vasculitis is attributable to chronic infection by which virus?
Immune-complexes composed of what?
HBsAg and anti-HBsAg = Chronic HBV
List the 4 vessels most often involved in Polyarteritis Nodosa in descending order of frequency.
- Kidneys
- Heart
- Liver
- GI tract
Vessels of which organ are characteristically spared in Polyarteritis Nodosa?
Pulmonary
Lesions seen in Polyarteritis Nodosa involve which part of the vessel and have a predileciton for which areas?
Only part of the vessel circumference w/ predilection for branch points
Classic Polyarteritis Nodosa is characterized by what morphological pattern of inflammation?
Segmental TRANMURAL necrotizing inflammation of small- to medium-sized arteries
During acute phase of Polyarteritis Nodosa the transmural inflammation of arterial wall shows a mixed inflammatory infiltrate and is often accompanied by what type of necrosis?
Fibrinoid necrosis
Polyarteritis Nodosa is typically a disease affecting which age group?
Typical course of the disease?
- Primarily young adults, but can also affect geriatric and pediatric pts
- Course is remitting and episodic, with long sx-free intervals
What is a “classic” presentation (signs/sx’s) of Polyarteritis Nodosa?
- Rapidly accelerating HTN + abdominal pain + bloody stools
- Diffuse myalgias and peripheral neuritis
What type of treatment can yield remissions or cures in 90% of pt’s with Polyarteritis Nodosa?
Immunosuppression
Acute arteritis affecting large, medium, and small-sized vessels, seen in infants and small children (<4 yo) is characteristic of what disease?
Kawasaki disease
Clinical significance of Kawasaki Disease stems from its predilection for which artery?
Leading to what manifestations?
- Coronary a.
- Aneurysms —> thrombosis or rupture –> acute MI
Vascular damage in Kawasaki Disease is primarily mediated by which immune cells?
T cells and monocytes/macrophages
What is the morphology of the vasculitis seen in Kawasaki Disease; differs from PAN how?
Dense transmural inflammatory infiltrate w/ LESS prominent fibrinoid necrosis than in PAN
Kawasaki disease typically presents with what signs/sx’s?
*First Aid Mnemonic
*CRASH and burn
- Conjunctival injection
- Rash (polymorphous -> desquamating)
- Adenopathy (cervical LN enlargement = mucocutaneous LN syndrome)
- Strawberry tongue (erythema and blistering of oral mucosa)
- Hand-foot changes (edema and erythema)
- Burn = FEVER
If Kawaksaki Disease is recognized early in its course treatment with what will sharply reduce the risk of symptomatic coronary artery disease?
IV immunoglobulin and Aspirin
Microscopic polyangiitis generally affects which type of vessels?
Capillaries + small arterioles and venules
How do the age and distribution of the lesions seen in Microscopic Polyangiitis differ from PAN?
Tend to be of the same age and are distributed more widely
Microscopic polyangiitis affects vessels of many organ systems, but which 3 systems are most common?
- Renal (necrotizing glomerulonphritis)
- Lungs (pulmonary capillaritis)
- Skin (palpable purpura)
Hypersensitivity vasculitis or leukocytoclastic vasculitis are another name for what?
Microscopic Polyangiitis
Microscopic polyangiitis can be a feature of which 3 immune disorders?
- Henoch-Schonlein purpura
- Essential mixed cryoglobulinemia
- Vasculitis assoc. w/ CT disorders
Segmental fibrinoid necrosis of the media and focal transmural necrotizing lesions w/ ABSENCE of granulomatous inflammation is characteristic of what type of vasculitis?
Microscopic polyangiitis
Which immune cells are seen infiltrating in microscopic polyangiitis, many of which are undergoing apoptosis and giving rise to the term leukocytoclastic vasculitis?
Neutrophils
What are the major clinical features (signs/sx’s) seen with microscopic polyangiitis?
- Hemoptysis
- Hematuria and Proteinuria
- Bowel pain or bleeding
- Muscle pain or weakness
- Palpable cutaneous purpura
Churg-Strauss Syndrome is a vasculitis affecting which size vessels?
Classically associated with what systemic manifestations?
- Small-vessel necrotizing vasculitis
- ASTHMA, ALLERGIC rhinitis, lung infiltrates, peripheral HYPER-eosinophilia, and extravascular necrotizing granulomata
Churgg-Strauss syndrome may have inflammation that resembles PAN or microscopic polyangiitis with the addition of what 2 things?
Eosinophils and Granulomas = Granulomatous, necrotizing vasculitis w/ eosinophilia
What is the primary manifestation of Churg-Strauss Syndrome affecting the kidneys?
Focal and segmental glomerulosclerosis
What is the primary manifestation of Churg-Strauss Syndrome affecting the myocardium?
Clinically significant why?
- Cardiomyopathy w/ eosinophilic infiltrates
- Accounts for HALF the deaths in this syndrome
Cutanous involvement of Churg-Strauss Syndrome presents with what?
Palpable Purpura
Behcet Disease is a vasculitis of small-to medium-vessels what classically presents with what triad?
1) Recurrent oral apthous ulcers
2) Genital ulcers
3) Uvetis
Which HLA haplotype is associated with Behcet Disease?
HLA-B51
Vessel inflammation in Behcet Disease is due to what inflammatory cell type?
Recruited by which T cells?
- Neutrophilic inflammation
- Recruited by TH17 cells
Mortality seen in Behcet Disease is related to what 2 complications?
- Severe neurologic involvement
- Rupture of vascular aneurysms
Granulomatosis with Polyangitis (Wegener granulomatosis) is a necrotizing vasculitis characterized by a triad of what?
1) Necrotizing granulomas of upper or lower respiratory tract, or both
2) Necrotizing or granulomatous vasculitis most prominenetly in lungs
3) Focal necrotizing, often CRESCENTERIC, glomerulonephritis
Granulomatosis with polyangiitis is a form of hypersensitivity mediated by what?
T-cell-mediated hypersensitivity
PR3-ANCAs (aka c-ANCA) is associated with what form of non-infectious vasculitis?
Granulomatosis w/ polyangiitis (Wegener granulomatosis)
Which non-infectious vasculitis is characterized by the presence of granulomas and a dramatic response to immunosuppressive therapy?
Granulomatosis w/ polyangiitis (Wegener granulomatosis)
Which sex is more often affected by granulomatosis with polyangiitis and at what age?
M > F; average age 40 yo
What are the classic features (signs/sx’s) of granulomatosis with polyangiitis?
- Persistent pneumonitis w/ bilateral nodular and cavitary infiltrates
- Chronic sinusitis
- Nasopharyngeal ulcerations
- Evidence of renal disease
How serious is granulomatosis with polyangiitis if left untreated?
Rapidly fatal w/ 80% mortality at one year
What are the morphological characteristics of the granulomas seen in the upper respiratory tract of someone with granulomatosis with polyangiitis?
Granulomas w/ geographic patterns of CENTRAL necrosis
The necrotizing granulomas seen in granulomatosis with polyangiitis are surrounded by zones of what?
Resembles?
- Zones of proliferating fibroblasts assoc. w/ giant cells and leukocytic infiltrate
- Reminiscent of mycobacterial or fungal infections
What may be seen radiographically in the lower respiratory tract of pt w/ granulomatosis with polyangiitis as multiple necrotizing granulomas coalesce?
Radiographically visible nodules that can also cavitate
Which renal lesions may be seen early on in granulomatosis with polyangiitis?
Eventually progress to what in late stages?
- Focal and segmental glomerulonephritis
- Crescenteric glomerulonephritis
Thromboangiitis obliterans (Buerger disease) is characterized by what type of vasculitis and especially in which arteries?
Occasional secondary extension to affect what?
- Segmental, thrombosing, acute and chronic vasculitis of small- and medium-vessels
- Principally the radial and tibial arteries w/ occasional 2’ extension to veins and nerves of the extremities
Thromboangiitis obliterans (Buerger disease) occurs almost exclusively in which patients and at what age?
Heavy cigarette smokers before age 35
Most patients with Thromboangiitis obliterans (Buerger disease) have hypersensitivity to intradermally injected what?
Tobacco products
What are 3 ethnic groups have higher incidences of Thromboangiitis obliterans (Buerger disease)?
- Israeli
- Indian subcontinent
- Japanese
The acute and chronic inflammation seen in Thromboangiitis obliterans (Buerger disease) is accompanied by what other morphological feature?
Luminal thrombus w/ small microabscesses composed of neutrophils surrounded by granulomatous inflammation
What are the early manifestations of Thromboangiitis obliterans (Buerger disease)?
- Raynaud’s
- Leg pain induced by exercise that is relieved on rest
- Instep foot pain induced by exercise
- Superficial nodular phlebitis (venous inflammation)
The vascular insufficiency of Thromboangiitis obliterans (Buerger disease) tends to be accompanied by what type of pain/when?
Chronic extremity ulcerations eventually progress to?
- Severe pain even at rest - due to neural involvement
- Progress to frank gangrene of extremities
Which 3 organisms can directly invade vessels and cause infectious vasculitis?
- Pseudomonas
- Aspergillus
- Mucor
Vascular invasion by organisms resulting in infectious vasculitis typically occurs in association with what, but can also less commonly occur via which route?
- Part of localized tissue infection
- Less commonly via hematogenous spread
Vascular infections can weaken arterial walls and can result in what clinically significant events?
- Mycotic aneurysms
or
- Induce thrombosis and infarction (i.e., thrombosis of meningal vessels in meningitis —> infarction of underlying brain)
How does Primary Raynaud’s vs. Secondary differ in their symmetry of involvement of the digits?
- Primary has symmetrical involvement of the digits
- Secondary has asymmetrical involvement of the digits
Secondary Raynaud’s may be a component of other arterial diseases such as what?
- SLE
- Scleroderma
- Thromboangiitis obliterans
Excessive vasoconstriction of myocardial arteries or arterioles which may cause ischemia or infarct is known as what?
Cardiac Raynaud
What are endogenous and exogenous agnts which are vasoactive mediators and can precipitate prolonged myocardial vessel contraction?
- Endogenous = epinephrine, pheochromocytoma
- Exogenous = cocaine or phenylephrine
Varicose veins are abnormally dilated, tortous veines produced by prolonged, increased intraluminal pressure and most often affect which veins?
Superficial veins of the upper and lower legs
Secondary tissue ischemia resulting from chronic venous congestion and poor vessel drainage results in what skin abnormalities?
- Stasis dermatitis (aka “brawny induration”)
- Ulcerations
- Poor wound healing and superimposed infections
How frequent do emboli arise from superficial LE veins?
Rarely
What is the most serious potential complication associated with DVT’s and is often the first manifestation of thrombophlebitis?
Pulmonary Embolism
Patients with what types of cancer and in which locations are at increased risk for thrombophlebitis, why?
- Adenocarcinoma of lung, ovary, pancreas
- Mucin-producing adenocarcinomas (mucin is thrombogenic)
- May occur as paraneoplastic syndrome, related to elaboration of procoagulant factors by tumor cells
Which factors associated with slow venous return increase the risk for DVT’s?
- Prolonged immobilization = MAJOR
- Pregnancy
- CHF
- Obesity
In the setting of systemic hypercoagulability, including genetic hypercoagulability, and cancers, what is the classical sign of venous thromboses?
- Appear at one site, dissapear, and then occur at another site
- Migratory thrombophlebitis (Trousseau sign)
What are the major causes of Superior Vena Cava Syndrome?
- Neoplasms (i.e., bronchogenic carcinoma or mediastinal lymphoma)
- Less commonly aortic aneurysms
Obstruction associated with superior vena cava syndrome produces what characteristic clinical complex?
- Marked DILATION of the veins of the: head, neck, and arms w/ CYANOSIS
- If pulmonary vessels compressed –> respiratory distress
Which 2 cancers have a tendency to grow within veins and may ultimately lead to inferior vena cava syndrome?
May also be caused by thrombosis from where?
- Hepatocellular carcinoma
- Renal cell carcinoma
- Thrombosis of the hepatic, renal, or LE veins which propogate cephalad
What are the signs/sx’s associated with inferior vena cava syndrome?
With renal involvement?
- Marked LE edema + distention of superficial collateral veins of lower abdomen
- Renal involvement —> MASSIVE proteinuria
Which bacteria is most commonly responsible for Lymphangitis?
group A β-hemolytic strep
Red, painful subcutaneous streaks w/ painful enlargement of the draining LN’s, is characteristic of what?
Lymphangitis
Port wine stains a special form of nevus flammeus, found within the distribution of the trigeminal nerve are associated with what congenital disorder?
Sturge-Weber Syndrome (encephalotrigeminal angiomatosis)
Sturge-Weber syndrome is associated with what clinical findings?
- Port wine nevi in trigeminal distribution
- Ipsilateral venous angioma in cortical leptomeninges
- Mental retardation + Seizures
- Hemiplegia
- Skull radio-opacities
What are the common sites for hemangiomas?
- Skin and mucous membranes of HEAD and NECK
- Liver
What is the most common type of hemangioma and where are they found?
- Capillary hemangioma
- Skin, subcutaneous tissues, and mucous membranes of the mouth, lips, liver, spleen, and kidneys
Which type of hemangioma is very common in newborns and often presents with multiple lesions, growing rapidly for a few months, and then regressing by age 7?
Juvenile Hemangioma (“strawberry type”)
How do Cavernous Hemangiomas differ in terms of infiltration and regression as compared to Capillary Hemangiomas?
- Are more infiltrative and frequently involve deep structures
- Do NOT spontaneously regress
- Locally destructive!
How do Cavernous Hemangiomas appear histologically?
- Unencapsulated mass
- Large, cavernous blood-filled vascular spaces
- Separated by CT stroma
What is the characteristic histology of Capillary Hemangiomas?
Thin-walled capillaries w/ scant stroma
Which type of hemangioma is commonly seen in VHL disease and where are the lesions most often seen?
- Cavernous hemangiomas
- Cerebellum, brain stem, retina, pancreas, and liver
What are 3 sequelae commonly associated with Cavernous Hemangiomas?
- Dystrophic calcifications
- Traumatic ulceration
- Intravascular thrombosis
Which subtype of capillary hemangioma presents as a rapdily growing red pedunculated lesion on the skin, gingival, or oral mucosa which often ulcerate and bleed easily?
Pyogenic granulomas
Simple (capillary) lymphangiomas can arise in the head, neck, and axillary regions and appear very similar to capillary hemangiomas, but can be differentiated how?
Absence of RBC’s
Cavernous lymphangiomas (cystic hygromas) are typically found where and in whom?
Common features?
- Neck or axilla of children
- Can occasionally be enormous (up to 15 cm) and may fill axilla or produce gross deformities of the neck.
Cavernous lymphangiomas (cystic hygromas) are a common feature of which congenital disorder?
Turner Syndrome
What are the histologic findings associated with cavernous lymphangiomas (cystic hygromas)?
- Massively dilated lymphatic spaces lined by endothelial cells
- Separated by intervening CT stroma containing lymphoid aggregates
What are the characteristics of Glomus Tumor (Glomangioma)?
Arise from what cells and are most often found where?
- Benign but VERY painful tumor
- Arising from modified smooth m. cells of the glomus bodies
- Most commonly in distal portion of the digits, especially under fingernails
Bacillary Angiomatosis is a vascular proliferation most commonly arising in whom and is due to what organism?
- Immunocompromised hosts (i.e., AIDS)
- Gram negative bacilli of Bartonella family
The bacillary angiomatosis induced by B. henselae infection is caused by induction of which host factors and upregulation of?
HIF-1 –> ↑ VEGF
How do the skin lesions in Bacillary Angiomatosis appear both grossly and microscopically?
- Grossly = red nodules and papules, or rounded SQ masses
- Histo = capillary proliferation w/ plump epitheloid endothelial cells exhibiting nuclear atypia and mitoses
What stain can help visualize the Bartonella bacilli associated with Bacillary Angiomatosis?
Warthin-Starry Silver
The infections and lesions associated w/ Bacillary Angiomatosis can be cleared with what med?
Macolide antibiotics (i.e., erythromycin)
How does the gross morphology of the lesions associated with Bacillary Angiomatosis differ from Kaposi Sarcoma?
- Bacillary = raised lesions
- Kaposi = flat lesions
Classic kaposi sarcoma is a disease most often seen in whom and where?
Older men of Mediterranean, Middel Eastern, or Eastern European descent
Which types of Kaposi Sarcoma are not associated with HIV?
- Classic KS
- Endemic African KS
- Transplant-associated KS
How does classic kaposi sarcoma typically manifest?
Most common location and spreads how?
- Multiple red-purple skin plaques or nodules
- Usually in distal LE; progressively ↑ in size and number and spread proximally
Endemic African kaposi sarcoma differs from classic KS in that it more frequently involves what?
Lymph nodes
How great of risk are transplant patients at for transplant-associated kaposi sarcoma?
100x ↑ risk
Which structures are most often involved in Transplant-Associated KS?
Lymph nodes, viscera, and mucosa
What is the most common HIV-related malignancy worldwide?
AIDS-associated (epidemic) KS
AIDS-associated (epidemic) KS frequently involves what structures and follows what course?
Lymph nodes and disseminates widely to viscera EARLY in its course
The nodular lesions seen in KS have what histological features and cells?
Sheets of plump, proliferating spindle cells
In classic KS, the cutaneous lesions progress through what 3 stages?
- Patches –> red, purple macules confined to distal LE’s
- Raised plaques –> as lesions spread prox.
- Nodular lesions –> distinctly neoplastic; sheets of plump proliferating spindle cells in dermis and SQ tissues
Which treatment is usually adequate for excellent prognosis in cases of Classic KS?
Surgical resection
Which therapy has greatly reduced the frequency of KS in HIV infected patients?
Anti-retroviral therapy
Vascular tumor occurring around medium and large-sized veins with neoplastic cells that are plump and often cuboidal is characteristic of?
Epitheliod Hemangioendothelioma
Hepatic angiosarcoma is associated with exposures to what?
- Arsenic (i.e., pesticides)
- Thorotrast (radioactive constrast agent)
- Polyvinyl Chloride (widely used plastic)
Angiosarcomas most often occur in which sex?
Either = NO gender predilection; typically older adults
Angiosarcomas may arise from lymph edema, classically where and in what setting?
Arise from which vessels?
- Ipsilateral UE years after radical masectomy (i.e., w/ LN resection) for breast cancer
- Arising from lymphatic vessels (lymphangiosarcoma)
How invasive and what is the risk of metastasis for angiosarcomas?
5-year survivial?
- Locally invasive and can readily metastasize
- 5-year survival around 30%
What is the gross morphology of cutaneous angiosarcomas?
- Begin as multiple small and asymptomatic red papules or nodules
- Eventually become large, fleshy masses of red-tan to gray-white tissue w/ margins blurring into surrounding structures
- Central areas of necrosis and hemorrhage common
In angiosarcomas what kind of differentiation can be seen?
- ALL degrees of differentiation may be seen:
- From plump, atypical endothelial cells forming vascular channels
- Wildly undifferentiated tumors w/ solid spindled appearance and no discernible blood vessels
The endothelial origin of Angiosarcomas can be demonstrated with staining for what?
- CD31
- von Willebrand factor
Angiosarcomas most commonly is found in which 4 locations?
- Skin
- Liver
- Breast
- Soft tissue
Small bore artificial grafts generally fail as a result of what 2 complications?
If small bore replacement required, best to use which grafted vessels?
- Thrombosis or intimal hyperplasia at jct. of the graft
- Use saphenous vein or left internal mammary arteries (best option)
