Vascular Pathology 2 Flashcards
Vasculitis
Inflammation of vessels
Clinical presentation: depend on location affected and often have nonspecific S/S:
Fever, malaise, arthralgias, myalgias
Infectious vs noninfectious vasculitis
Noninfectious vasculitis: immunologic injury - immune complex deposition or autoantibodies; indicates immunosuppressive therapy
Infectious vasculitis - pathogenic organisms invading vessel wall
Immune complex vasculitis
Deposition of antigen-antibody complexes in vascular walls
◦ Incites an inflammatory reaction within the wall
◦ Antigen is often unidentified
May be seen in
◦ Systemic immunologic diseases (eg, SLE)
◦ Drug hypersensitivity
◦ Secondary to exposure to infectious agent
Antineutrophil cytoplasmic antibodies
Heterogeneous group of antibodies reactant with cytoplasmic enzymes in neutrophil granules, monocytes, and endothelial cells
◦ Anti-proteinase-3 (previously c-ANCA)
◦ Anti-myeloperoxidase (previously p-ANCA)
ANCA titers generally follow disease severity
ANCAs activate neutrophils, which then release reactive oxygen species
Giant cell (temporal) arteritis
Most common vasculitis in older patients, may present with constitutional symptoms
Chronic (T cell mediated) inflammation of arteries in the head, especially the temporal arteries
◦ Medial granulomatous inflammation, often with multinucleated giant cells
◦ Fragmentation of the elastic lamina
◦ Sites of involvement within an artery may be patchy and focal
◦ Healed sites of inflammation show scarring of the media and intimal thickening
Involvement of the ophthalmic artery may lead to vision loss
Takayasu arteritis
Similar histologic findings as those seen in giant cell arteritis, except ◦ Involves the aortic arch and major branch vessels (“pulseless disease”)
◦ Pulmonary, coronary and renal arteries may be involved
◦ Younger age group (<50)
May present with weak pulse and low blood pressure in the upper extremities
Polyarteritis nodosa (PAN) incidence
Systemic vasculitis, likely immune complex mediated
Involves (decreasing order of frequency)
◦ Renal vessels, heart, liver, GI tract
◦ Pulmonary vessels are spared
May affect any age group, but classically young adult
Almost 1/3 of patients have chronic hepatitis B
◦ HBsAg-HBsAb complexes are found in the involved vessels
Polyarteritis nodosa (PAN) characteristics
Transmural necrotizing inflammation, containing neutrophils, eosinophils, lymphocytes and macrophages
Fibrinoid necrosis of the vessel wall
Sites of inflammation are typically not circumferential
The inflamed vessel wall my become susceptible to ◦ Thrombus formation/occlusion
◦ Aneurysm
◦ Rupture
Immunosuppressive therapy usually effective
Kawasaki disease
Acute arteritis of infants and small children (80% ≤ 4 years)
Often involves the coronary arteries
◦ Affected sites may form aneurysms → thrombosis or rupture → acute MI
Presenting picture is usually erythema of the conjunctiva, oral mucosa, palms and soles; rash, and cervical lymph node enlargement
◦ “Mucocutaneous lymph node syndrome”
Usually self-limited, but IV Ig and aspirin are indicated to lower the risk of a coronary event
Microscopic polyangiitis
Necrotizing vasculitis involving arterioles, capillaries and venules
Affects vessels of many organ systems
◦ Renal glomeruli and lung capillaries most common
Most cases associated with MPO-ANCA
Segmental necrotizing inflammation with fibrinoid necrosis
◦ Many apoptotic neutrophils are usually seen
◦ “leukocytoclastic vasculitis”
Churg-Strauss Syndrome
Small vessel necrotizing vasculitis, associated with
◦ Asthma, allergic rhinitis, hypereosinophilia, lung infiltrates, extravascular granulomas
Inflammation may resemble PAN or m. polyangiitis, with the addition of eosinophils and granulomas
Less than half show ANCA positivity
Many organ systems may be involved.
Behcet disease
Vasculitis of small to medium vessels with the following additional findings:
◦ Aphthous ulcers of the oral cavity
◦ Genital ulcers
◦ uveitis
The vessel inflammation is neutrophilic and morphologically nonspecific, may involve visceral organ systems with subsequent aneurysm formation
Associated with HLA-B51
Granulomatosis with polyangiitis features
Necrotizing vasculitis featuring:
◦ Necrotizing granulomas of the upper and/or lower respiratory tracts
◦ Necrotizing or granulomatous vasculitis, most prominently in the respiratory tract
◦ Focal necrotizing, often crescentic, glomerulonephritis
Associated with PR3-ANCA (up to 95% of cases)
◦ Upper respiratory tract: sinonasal and pharyngeal inflammation with granulomas and vasculitis
◦ Lower respiratory tract: multiple necrotizing granulomas, which may coalesce and cavitate
Immunosuppressive therapy is usually successful (untreated, 80% mortality in one year)
Clinical features of Granulomatosis with polyangiitis
◦ M >F
◦ Avg age of 40
◦ Most patients have persistent pneumonitis and sinusitis, renal disease, and nasopharyngeal ulceration
Thromboangiitis obliterans
Acute and chronic thrombosing vasculitis of small and medium vessels, especially
◦ Tibial arteries
◦ Radial arteries
May lead to vascular insufficiency of the extremities
Patients are almost always smokers, and young adults
Inflammation may extend to involve adjacent veins and nerves (leading to pain)
Chronic ulcerations, which may lead to gangrene
Raynaud phenomenon
excessive vasospasm of small arteries and arterioles, especially in the fingers and toes
Primary Raynaud phenomenon
◦ Induced by cold or emotion; symmetric involvement of the digits ◦ Estimated 3-5% general population; young women
◦ Benign course
Secondary Raynaud phenomenon
◦ A component of another arterial disease such as SLE, scleroderma, or thromboangiitis obliterans; asymmetric involvement of digits
◦ Worsens with time
Myocardial vessel vasospasm
Excessive vasoconstriction of myocardial arteries or arterioles (“cardiac Raynaud”) may cause ischemia or infarct
Usually caused by circulating vasoactive agents, which may be endogenous
◦ epinephrine
Or exogenous
◦ cocaine
Varicose veins
Abnormal dilation of veins with valvular incompetence, secondary to sustained intraluminal pressure
◦ Stasis, congestion, thrombus, edema and ischemia of overlying skin (stasis dermatitis)
Embolism from thrombi of superficial lower extremity veins is rare.
Esophageal varices
Portal hypertension (often due to cirrhosis) opens portosystemic shunts which direct blood to veins at the gastroesophageal junction ◦ Esophageal varices (clinically important because they may fatally rupture)
the rectum
◦ hemorrhoids
and periumbilicus
◦ Caput medusa
Hemorrhoids
Dilation of the venous plexus at the anorectal junction
Extremely common, and cause pain, bleeding, and may ulcerate
Thrombophlebitis
Venous thrombosis and inflammation
Almost always (>90%) involves deep veins in the legs, and can be completely asymptomatic
Single most important risk factor for developing a deep venous thrombosis (DVT) in the LE is prolonged inactivity/immobilization
Systemic hypercoagulability may also increase risk of DVT
Pulmonary embolism is the most serious potential consequence
Migratory thrombophlebitis (Trousseau sign)
◦ Patients with cancer may experience hypercoagulability as a paraneoplastic syndrome
◦ Particularly seen with mucin-producing adenocarcinomas (mucin is thought to be thrombogenic)
◦ In the classic case, venous thromboses appear at one site, disappear, and reappear at a different site
◦ Associated with adenocarcinomas of the lung, ovary, pancreas
Hemangiomas - general
common tumors showing a localized increase in neoplastic blood vessels
Common sites include skin and mucous membranes of the head and neck, and in the liver
Congenital (juvenile, or “strawberry”) hemangiomas often regress
Capillary hemangioma
most common
thin-walled capillaries, tightly packed together
Cavernous hemangioma
◦ Irregular, dilated vascular channels making a lesion with an indistinct border
◦ More likely to involve deep tissue, more likely to bleed
Pyogenic granuloma (lobular capillary hemangioma)
◦ type of capillary hemangioma (not pyogenic, not a granuloma)
◦ Rapidly growing, often in oral mucosa (where they may ulcerate)
Simple lymphangioma
◦ Appear very similar to capillary hemangiomas, but without RBCs
◦ Subcutis of head/neck and axillae
Cavernous lymphangioma (cystic hygroma)
◦ Neck or axilla of children
◦ Can be large (up to 15 cm)
◦ Large cavernous lymphangiomas of the neck are often seen in Turner syndrome
Glomus tumor
Benign tumors arising from glomus bodies, and most often appear in distal fingers
Of smooth muscle origin rather than endothelial
Painful
Bacillary angiomatosis
A vascular proliferation in response to gram negative Bartonella bacilli
Occurs on the skin of immunocompromised patients
◦ lesions localized, forming red papules
◦ Microscopically, a proliferation of capillaries with plump endothelial cells
◦ The bacteria can be identified with PCR, or visualized with a Warthin-Starry stain
◦ Macrolide antibiotics are effective
Epithelioid hemangioendothelioma
Intermediate vascular tumor
neoplastic endothelial cells are plump and cuboidal, resembling epithelium
Vascular channels may be difficult to recognize.
variable clinical behavior, with metastasis in 20-30%
Kaposi sarcoma
Intermediate vascular tumor
Caused by human herpesvirus 8 (HHV8)
AIDS-associated Kaposi sarcoma
The most common form seen in the US.
Most common AIDS-related malignant tumor.
May spread to lymph nodes and viscera.
Classic Kaposi sarcoma
Older men from Middle Eastern, Mediterranean or Eastern European descent.
NOT associated with HIV.
Tumors localized to skin.
Endemic African Kaposi sarcoma
Not associated with HIV.
Patients < 40.
Can involve lymph nodes.
Transplant-associated Kaposi sarcoma
Not associated with HIV, but with T-cell immunosuppression.
Can spread to lymph nodes and viscera.
Angiosarcoma
Malignant endothelial tumor
Age: older; M = F
May occur anywhere, but the most common sites are ◦ Skin
◦ Soft tissue
◦ Breast
◦ liver
Locally invasive and may metastasize
5 year survival around 30%
