Exam IV: Pathology of Vascular Interventions

Question 1

Varicose Veins

Answer 1

Abnormally dilated, tortuous veins (serpentine)
Causes prolonged, increased intraluminal pressure and loss of vessel wall support
Involvement: superficial veins of the upper and lower leg

Question 2

Varicose Veins: Causes and Complications

Answer 2

Familial tendency: development of varicosities due to defective development of vein walls

Most disabling complications:

1. Persistent edema in the extremity
2. Ischemic skin changes: stasis dermatitis and cutaneous ulcerations due to poor wound healing and superimposed infections; can develop chronic varicose ulcers

Question 3

Esophageal Varices

Answer 3

Liver cirrhosis causes portal vein hypertension, which opens porto-systemic shunts to increase blood flow into veins at esophagealgastic junction

Development of:

1. Esophageal varices
2. Rectum (hemorrhoids)
3. Periumbilical veins of abdominal wall (caput medusa)

Most important: rupture causes massive (fatal) upper GI hemorrhage

Question 4

Thrombophlebitis/Phlebothrombosis

Answer 4

Venous thrombosis + inflammation

Venous thrombosis: potentiated by cardiac failure, neoplasia, pregnancy, obesity, post-op state, prolonged bed rest/immobilization

Deep leg veins account for > 90% of thrombophlebitis cases

Riding in a plane for a long time without moving
Surgery on knee or hip, or some type of immobilization then DVT to PE

Question 5

Thrombophlebitis/Phlebothrombosis: Other Sites

Answer 5

Other sites:
Periprostatic venous plexus (males)
Pelvic venous plexus (females)
Large veins in the skull and the dural sinuses (infection or inflammation)
Portal vein thrombosis
Peritoneal infections, appendicitis, salpingitis, and pelvic abscesses

Question 6

Thrombophlebitis/Phlebothrombosis: Systemic Hypercoagulability

Answer 6

Carcinoma: adenocarcinomas cause paraneoplastic syndrome, which is a pro-coagulant state caused by factors by the tumor cells

Migratory thrombophlebitis: AKA thrombophlebitis migrans
Trousseau sign of malignancy
Venous thrombi occur in one site and reappear elsewhere

Question 7

Pulmonary Embolism (PE)

Answer 7

Serious complication of DVT
Fragmentation/detachment of whole venous thrombus
First manifestation of thrombophlebitis

Question 8

Lymphangitis

Answer 8

Bacterial infections spread into and through lymphatics:
Acute inflammation in lymphatic channels/nodes
Most common agent: Group A β-hemolytic streptococci

Affected lymphatics:
Dilated and filled with inflammatory infiltrate composed of neutrophils (acute) and histiocytes (starting to become chronic)
Extends through the vessel wall
Perilymphatic tissues
Cellulitis or focal abscesses (severe cases)

Question 9

Clinical Features of Lymphangitis

Answer 9

Painful subcutaneous red streaks extend along the course of lymphatics

Painful enlargement of regional lymph nodes

If lymph nodes fail to block bacteria they drain into venous circulation causing bacteremia or septicemia

Question 10

Primary Lymphedema

Answer 10

Isolated congenital defect (simple congenital lymphedema)
Familial Milroy disease: heredofamilial congenital lymphedema that causes lymphatic agenesis or hypoplasia
The patient will have no lymph nodes or no nodes in that appendage

Question 11

Secondary (Obstructive) Lymphedema

Answer 11

Occlusion of lymphatic vessels causing abnormal accumulation of interstitial fluid

Most common causes:

1. Malignant tumors obstructing lymphatic channels or regional lymph nodes
2. Surgical procedures that remove regional groups of lymph nodes- axillary lymph nodes in radical mastectomy
3. Post-irradiation fibrosis
4. Filariasis- causes elephantitis; larvae of microfilariae that hatch and block fluid
5. Post-inflammatory thrombosis and scarring

Question 12

Persistence of Lymphedema

Answer 12

Increase of subcutaneous interstitial fibrous tissue
Consequent enlargement of affected part
Induration: peau d’orange (orange peel) appearance and skin ulcers

Question 13

Lymphedema in Cavities

Answer 13

Milky collections of lymph in various spaces
Rupture of dilated lymphatics due to obstruction of lymphatics by infiltrating tumor

Categories:
Chylous ascites (peritoneum)
Chylothorax (pleural cavity)
Chylopericardium (pericardium)

Question 14

Benign Hemangiomas

Answer 14

Locally aggressive lesions with infrequent metastases
Rarely highly malignant angiosarcomas

Primary tumors of large vessels:
Aorta, pulmonary artery, and vena cava
Extremely rare and mostly connective tissue sarcomas

Extremely common tumors
Increased numbers of normal or abnormal vessels filled with blood
Majority are superficial lesions in head or neck
Internal lesions: 1/3rd in the liver
Many types/variations: capillary, cavernous, and pyogenic granuloma

Question 15

Vascular Neoplasms

Answer 15

Endothelium-derived: hemangioma, lymphangioma, angiosarcoma
Arise from cells that support and/or surround blood vessels such as endothelial and glomus cells
Glomus tumor, hemangiopericytoma

Question 16

Capillary Hemangioma

Answer 16

Most common variant
Composed of a proliferation of benign capillaries

Locations:
Skin and subcutaneous tissues
Mucous membranes of the oral cavities and lips
Liver, spleen, and kidneys

Question 17

Capillary Hemangioma Characteristics

Answer 17

Bright red to blue
Millimeters to several centimeters in diameter
Flat or elevated
Unencapsulated aggregates of closely packed, thin-walled capillaries- blood-filled and lined by flattened endothelium
Scant connective tissue stroma separates vessels
Lumens may be partially or completely thrombosed
Microscopically: everything looks well maintained, just see a lot of capillaries

Question 18

Capillary Hemangioma: Strawberry Type

Answer 18

AKA Juvenile hemangioma of the skin of newborns
Extremely common
May be multiple
Grows rapidly in the first few months
Fades at 1 to 3 years of age
Completely regresses by age 7 (75% to 90% of cases)

Question 19

Cavernous Hemangioma

Answer 19

Large, dilated vascular channels
Less well circumscribed
Involve deep structures
Brain hemangiomas–most problematic because pressure symptoms or rupture
Component of von Hippel-Lindau disease: cerebellum, brain stem, or retina

Question 20

Cavernous Hemangioma Characteristics

Answer 20

Red-blue, soft, spongy masses
1 to 2 cm in diameter and sharply defined
Composed of large, cavernous blood-filled vascular spaces separated by a modest connective tissue stroma
Intravascular thrombosis with associated dystrophic calcification (will degenerate over time and calcifications develop)

Question 21

Pyogenic Granuloma

Answer 21

Rapidly growing pedunculated red nodule
Skin, gingival or oral mucosa
Bleeds easily; often ulcerated
Proliferating capillaries
Extensive edema
Acute and chronic inflammatory infiltrate
Purulent debris producing = see neutrophils
Pyogenic: capillary hemangioma + acute inflammation, irritated, ulcerated, or bleeding

Question 22

Lymphangiomas

Answer 22

Benign lymphatic analogues of blood vessel hemangiomas

Simple (Capillary) Lymphangioma:
Small lymphatic channels
Head, neck, and axillary subcutaneous tissues
Elevated or pedunculated; 1 to 2 cm in diameter
Networks of endothelium-lined spaces distinguished from capillary channels only by the absence of erythrocytes

Question 23

Cavernous Lymphangioma (Cystic Hygroma)

Answer 23

Neck or axilla of children usually with other genetic conditions like Turner syndrome
Can be very large (15 cm in diameter) and may fill the axilla and form gross deformities of neck
Massively dilated lymphatic spaces lined by endothelial cells and separated by intervening connective tissue stroma
Lymphoid aggregates
Cavernous angioma - RBCs = cystic hygroma

Question 24

Glomus Tumor (Glomangioma)

Answer 24

Benign, exquisitely painful tumors

Arises from modified smooth muscle cells of the glomus body, which are specialized arteriovenous structure involved in thermoregulation

Located anywhere in the skin most commonly found in the distal portions of the digits and under fingernails

“Patient that is very tough that is crying in pain over this dot under fingernail” = glomus tumor

Question 25

Glomus Tumor (Glomangioma) Characteristics

Answer 25

Round, slightly elevated, red-blue Firm nodules (<1 cm in diameter) Aggregates, nests, and masses of specialized glomus cells Branching vascular channels Microscopically: nice round nodule, but made up of specialized purple glomus cells

Question 26

Vascular Ectasias: Nevus Flammeus

Answer 26

Group of abnormally prominent capillaries, venules and arterioles that creates a focal red lesion usually in skin or mucous membranes Nevus Flammeus: “Birthmark" Most common form of ectasia Head or neck; light pink to deep purple Vascular dilation of blood vessels in dermis Doesn’t grow with child, stays the same size

Question 27

Vascular Ectasias: Port Wine Stain

Answer 27

Port wine stain- special form of nevus flammeus that grows with child Thickens skin surface Distribution of the trigeminal nerve or occasionally associated with Sturge-Weber syndrome AKA encephalotrigeminal angiomatosis Rare congenital disorder Associations: Venous angiomatous masses in cortical leptomeninges Ipsilateral facial port wine nevi Mental retardation, seizures, hemiplegia

Question 28

Spider Telangiectasia

Answer 28

Focal network of subcutaneous small arteries or arterioles Arranged in a radial fashion around a central core Non-neoplastic vascular lesion Blanches when pressure is applied to its center Face, neck, or upper chest Pregnant women or patients with cirrhosis from alcoholism

Question 29

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease)

Answer 29

Autosomal dominant disorder Multiple aneurysmal telangiectasias Skin and oral mucous membranes, respiratory, GI, urinary tracts Present from birth Lesions rupture (occasional): serious epistaxis (nosebleeds), GI bleed, or hematuria

Question 30

Bacillary Angiomatosis

Answer 30

Vascular proliferation Opportunistic infection in immunocompromised individuals Lesions involve skin, bone, brain, other organs Infection with gram-negative bacilli of the Bartonella family: 1. Bartonella henselae (cat-scratch disease) 2. B. quintana ("trench fever“)

Question 31

Bacillary Angiomatosis: Characteristics

Answer 31

Skin lesions: red papules and nodules and rounded subcutaneous masses Capillary proliferation with epithelioid endothelial cells Nuclear atypia and mitotic figures Lesions contain neutrophils, nuclear dust, and bacteria Diagnosis: polymerase chain reaction (PCR) Treatment: Macrolide antibiotics (erythromycin)

Question 32

Kaposi Sarcoma

Answer 32

Common in AIDS patients Four forms of the disease: 1. Chronic KS AKA classic or European KS 2. Lymphadenopathic KS AKA African or endemic KS 3. Transplant-associated KS 4. AIDS-associated (epidemic) KS

Question 33

Chronic Kaposi Sarcoma/European KS

Answer 33

Older men of Eastern European (Ashkenazi Jews) or Mediterranean descent Can see with underlying malignancy; not HIV Multiple red to purple skin plaques or nodules Distal lower extremities Increase in size and number; spread proximally Locally persistent; asymptomatic Remain localized to skin and subcutaneous tissue

Question 34

Lymphadenopathic KS/ African or Endemic KS

Answer 34

Same geographic distribution as Burkitt lymphoma Prevalent among South African Bantu children NOT associated with HIV Skin lesions are sparse Lymphadenopathy Extremely aggressive

Question 35

Transplant-Associated KS

Answer 35

Solid-organ transplantation on long-term immunosuppression Aggressive (even fatal) Nodal, mucosal, and visceral involvement Cutaneous lesions may be absent Lesions occasionally regress when immunosuppressive therapy is reduced, which risks organ rejection

Question 36

AIDS-Associated (Epidemic) KS

Answer 36

Originally found in 1/3rd of AIDS patients Male homosexuals Regimens of antiretroviral therapy: incidence is less than 1% Lymph nodes or viscera Disseminates/spreads widely early in disease

Question 37

Pathogenesis of Kaposi Sarcoma

Answer 37

Human herpesvirus-8 (HHV-8) KS-associated herpesvirus (KSHV) Member of the γ-herpesvirus subfamily Transmitted sexually and nonsexual routes (? Saliva)

Question 38

Kaposi Sarcoma: Three Stages

Answer 38

1. Patch 2. Plaque 3. Nodule

Question 39

Kaposi Sarcoma: Stage 1

Answer 39

Patch Red to purple macules Confined to the distal lower extremities Dilated irregular endothelial cell-lined vascular spaces Interspersed lymphocytes, plasma cells, and macrophages

Question 40

Kaposi Sarcoma: Stage 2

Answer 40

Plaque More purple than red Over time, spread proximally Larger, violaceous, raised Dermal accumulations of dilated, jagged vascular channels Lined and surrounded by plump spindle cells Extravasated red cells, hemosiderin-laden macrophages, and other mononuclear inflammatory cells

Question 41

Kaposi Sarcoma: Stage 3

Answer 41

Nodule Distinctly neoplastic Sheets of plump, proliferating spindle cells Dermis or subcutaneous tissues Small vessels and slit-like spaces: contain red cells More marked hemorrhage, hemosiderin pigment, and mononuclear inflammation Mitotic figures are common Heralds nodal and visceral involvement African and AIDS-associated variants

Question 42

Hemangioendothelioma

Answer 42

``` Wide spectrum of vascular neoplasms Epithelioid hemangioendothelioma Vascular tumor of adults Around medium-sized and large veins Plump and cuboidal tumor cells Inconspicuous well-defined vascular channels ```

Question 43

Angiosarcoma

Answer 43

Malignant endothelial neoplasms Varying histology: well-differentiated tumors (hemangiosarcoma) and anaplastic lesions Older adults--more commonly affected Skin, soft tissue, breast, and liver

Question 44

Hepatic Angiosarcoma

Answer 44

Associated with carcinogen exposures: 1. Arsenic (arsenical pesticides) 2. Thorotrast- radioactive contrast agent formerly used for radiologic imaging 3. Polyvinyl chloride (PVC) Long latent periods between initial exposure and tumor development

Question 45

Angiosarcoma: Setting of Lymphedema

Answer 45

Setting of lymphedema then develop angiosarcoma Ipsilateral upper extremity Several years after radical mastectomy with lymph node resection Tumor arises from lymphatic vessels (lymphangiosarcoma)

Question 46

Angiosarcoma Characteristics

Answer 46

Small, sharply demarcated, asymptomatic, red nodules Large, fleshy masses of red-tan to gray-white tissue Margins blend with surrounding structures Central areas of necrosis and hemorrhage Malignant tumor that forms vessels = looks like little red nodules and see it when hemorrhage See where highly vascularized like the heart Hard to delineate malignant tissue from normal tissue because no capsule

Question 47

Angiosarcoma: Microscopic Evaluation

Answer 47

Plump, anaplastic endothelial cells producing vascular channels Wildly undifferentiated tumors Solid spindle cell appearance and without definite blood vessels CD31 or von Willebrand factor Locally invasive; metastasize readily Aggressive tumors; 5-year survival rates approaching 30%

Question 48

Hemangiopericytoma

Answer 48

Rare neoplasm Derived from pericytes-myofibroblast-like cells arranged around capillaries and venules Slowly enlarging, painless masses Most common in lower extremities (thigh) and retroperitoneum Numerous branching capillary channels Gaping sinusoidal spaces enclosed within nests of spindle-shaped to round cells Recur after excision: about half will metastasize hematogenously to lungs, bone, or liver