DISEASES OF THE BLOOD VESSELS AND LYMPHATICS

Clent BanaayDOH-PCSHC Intern

EAMC Department of Pathology

Raynaud phenomenon Results from an

exaggerated vasoconstriction of digital arteries and arterioles

Pattern: Red White Blue

Primary Raynaud phenomenon (previously called Raynaud disease)

reflects an exaggeration of central and local vasomotor responses to cold or emotional stresses

Predilection for young women

Arterial wall structural changes appear in late course.

Benign

Long standing results in atrophy of the skin, SC and muscles

Secondary Raynaud phenomenon refers to vascular insufficiency of

the extremities secondary to arterial disease

SLE, scleroderma, Buerger disease, or even atherosclerosis

VEINS AND LYMPHATICS

VARICOSE VEINS

Abnormally dilated, tortuous veins produced by prolonged, increased intraluminal pressure and loss of vessel wall support.

When legs are dependent for prolonged periods, venous pressures in these sites can be markedly elevated (up to 10 times normal) and can lead to venous stasis and pedal edema, even in essentially normal veins (simple orthostatic edema).

Varicose dilation renders the venous valves incompetent and leads to stasis, congestion, edema, pain, and thrombosis.

sequelae include persistent edema in the extremity and ischemic skin changes, including stasis dermatitis and ulcerations; poor wound healing and superimposed infections can lead to chronic varicose ulcers

Other varicosities: Esophageal varices and Hemorrhoids

Thrombophlebitis and Phlebothrombosis

Sites: Deep leg veins- 90% periprostatic venous plexus in males pelvic venous plexus in females , large veins in the skull and the dural

sinuses (especially in the setting of infection or inflammation).

Peritoneal infections, including peritonitis, appendicitis, salpingitis, and pelvic abscesses

conditions associated with platelet hyperactivity e.g., polycythemia vera

Predisposing Factors:

Prolonged immobilization Systemic hypercoagulability Migratory

thrombophlebitis (Trousseau sign) Infection/ Inflammation

Signs and Symptoms

Distal edema, cyanosis, superficial vein dilation, heat, tenderness, redness, swelling, and pain may be entirely absent, especially in bedridden patients

Squeezing the calf muscles, or forced dorsiflexion of the foot (Homan sign).

Pulmonary embolism results from fragmentation or detachment of the whole venous thrombus

SUPERIOR VENA CAVAL SYNDROMES

caused by neoplasms that compress or invade the superior vena cava, such as bronchogenic carcinoma or mediastinal lymphoma

The obstruction produces a characteristic clinical complex that includes marked dilation of the veins of the head, neck, and arms and cyanosis.

Pulmonary vessels can also be compressed, causing respiratory distress.

Inferior vena caval syndrome

Caused by neoplasms that compress or invade the inferior vena cava (IVC) or by a thrombus from the hepatic, renal, or lower extremity veins that propagates upward

E.g. hepatocellular carcinoma and renal cell carcinoma

IVC obstruction induces marked lower extremity edema, distention of the superficial collateral veins of the lower abdomen, and with renal vein involvement massive proteinuria

LYMPHANGITIS AND LYMPHEDEMA

Lymphangitis is the acute inflammation elicited when bacterial infections spread into lymphatics group A β-hemolytic streptococci

lymphatics are dilated and filled with an exudate of neutrophils and monocytes;

these infiltrates can extend through the vessel wall into the perilymphatic tissues and, in severe cases, produce cellulitis or focal abscesses

Primary lymphedema occur due to an isolated congenital defect (simple

congenital lymphedema) or as the familial Milroy disease (heredofamilial congenital lymphedema),

Causes lymphatic agenesis or hypoplasia.

Secondary or obstructive lymphedema stems from blockage of a previously normal

lymphatic; such obstruction can result from :1. Malignant tumors obstructing either the lymphatic

channels or the regional lymph nodes   2.    Surgical procedures that remove regional groups

of lymph nodes (e.g., axillary lymph nodes in radical mastectomy)   

3. Post-irradiation fibrosis    4.     Filariasis    5. Post-inflammatory thrombosis and scarring

lymphedema the hydrostatic pressure in the lymphatics distal to

the obstruction ->increased interstitial fluid accumulation.

Persistence of this edema increased deposition of interstitial

connective tissue

brawny induration or peau d'orange (orange peel)

appearance of the overlying skin ulcers due to inadequate tissue

perfusion.

Milky accumulations of lymph in various spaces are designated

chylous ascites (abdomen), chylothorax, and chylopericardium;

these are caused by rupture of dilated lymphatics, typically

obstructed secondary to an infiltrating tumor mass.

Tumors of the Blood vessels

Vascular neoplasms

endothelium-derived arise from cells that support and/or

surround blood vessels (e.g., glomus tumor, hemangiopericytoma).

BENIGN VASCULAR TUMORS

MALIGNANT

produce obvious vascular channels filled with blood cells or lymph, lined by a layer of normal-appearing endothelial cells.   

--more cellular

--cytologic atypia,

--proliferative,

---mitotic figures

--do not form well-organized vessels.

--The endothelial derivation of neoplasms that do not form distinct vascular lumens

usually be confirmed by immunohistochemical demonstration of endothelial cell–specific markers such as CD31 or von Willebrand's factor

HEMANGIOMA

characterized by increased numbers of normal or abnormal vessels filled with blood

7% of all benign tumors of infancy and childhood; most are present from birth and expand along with the growth of the child

Mostly localized, involvement of a large portion of the bodyAngiomatosis

Capillary Hemangioma

Occur in the skin, subcutaneous tissues, and mucous membranes of the oral cavities and lips, as well as in the liver, spleen, and kidneys

Most common variant

hemangiomas are bright red to blue and vary from a few millimeters to several centimeters in diameter;

hemangiomas can be level with the surface of the skin or slightly elevated, and have an intact overlying epithelium

unencapsulated aggregates of closely packed, thin-walled capillaries, usually blood-filled and lined by flattened endothelium; vessels are separated by scant connective tissue stroma

Cavernous Hemangioma

exhibit large, dilated vascular channels; compared with capillary hemangiomas

less well circumscribed and more frequently involve deep structures

A component of von Hippel-Lindau disease

Cavernous hemangiomas are red-blue, soft, spongy masses 1 to 2 cm in diameter;

rare giant forms can affect large subcutaneous areas of the face, extremities, or other body regions

the mass is sharply defined but not encapsulated, and composed of large, cavernous blood-filled vascular spaces, separated by a modest connective tissue stroma

Pyogenic Granuloma rapidly growing pedunculated

red nodule on the skin, or gingival or oral mucosa; it bleeds easily and is often ulcerated

Roughly a third of the lesions develop after trauma

Looks like an exuberant granulation tissue

Pregnancy tumor (granuloma gravidarum) is a pyogenic granuloma that occurs infrequently (1% of patients) in the gingiva of pregnant women

Lymphangiomas Simple (Capillary)

Lymphangioma. Composed of small lymphatic

channels predominantly occurring in the head, neck, and axillary subcutaneous tissues.

slightly elevated or sometimes pedunculated lesions up to 1 to 2 cm in diameter.

Histologically, exhibit networks of endothelium-lined spaces that can be distinguished from capillary channels only by the absence of erythrocytes

Cavernous Lymphangioma (Cystic Hygroma) Found in the neck or axilla of

children, and rarely occur in the retroperitoneum

Seen in Turner syndrome Composed of massively dilated

lymphatic spaces lined by endothelial cells

Separated by intervening connective tissue stroma containing lymphoid aggregates

The tumor margins are not discrete and the lesions are not encapsulated

Glomus Tumor (Glomangioma)

Exquisitely painful tumors arising from modified smooth muscle cells of the glomus body, a specialized arteriovenous structure involved in thermoregulation

Resemble cavernous hemangiomas, glomus tumors constitute a distinct entity by virtue of their constituent cells

Morphology: Glomus tumor lesions are round,

slightly elevated, red-blue, firm nodules (usually <1 cm in diameter) that initially resemble a minute focus of hemorrhage.

Histologically, these are aggregates, nests, and masses of specialized glomus cells intimately associated with branching vascular channels, all within a connective tissue stroma.

tumor cells are small, uniform, and round or cuboidal, with scant cytoplasm and ultrastructural features akin to smooth muscle cells.

Vascular Ectasias

Common lesions characterized by local dilation of preexisting vessels; they are not true neoplasms. Telangiectasia is a term used for a congenital anomaly or acquired exaggeration of preformed vessels—usually in the skin or mucous membranes—composed of capillaries, venules, and arterioles that creates a discrete red lesions

Nevus Flammeus

Hereditary Hemorrhagic Telangiectasia (OslerWeber-Rendu Disease).

Spider Telangiectasia

Bacillary Angiomatosis

Vascular proliferation resulting from an opportunistic infection in immunocompromised individuals;

lesions can involve skin, bone, brain, and other organs

caused by infection with gram-negative bacilli of the Bartonella family.

Skin lesions are red papules and nodules, or rounded subcutaneous masses; histologically,

there is capillary proliferation with prominent epithelioid endothelial cells exhibiting nuclear atypia and mitoses

Kaposi Sarcoma INTERMEDIATE-GRADE (BORDERLINE) TUMORS

4 forms of Kaposi sarcoma:1. Chronic KS (also called classic

or European KS) chronic KS can be associated

with an underlying second malignancy or altered immunity

not associated with human immunodeficiency virus (HIV).

2. Lymphadenopathic KS (also called African or endemic KS)

not associated with HIV. Skin lesions are sparse, and patients present

instead with lymphadenopathy due to KS involvement

3. Transplant-associated KS occurs in the setting of solid-organ

transplantation with its attendant long-term immunosuppression.

It tends to be aggressive (even fatal) with nodal, mucosal, and visceral involvement.

4. AIDS-associated (epidemic) KS

KS was originally found in a third of AIDS patients

95% of KS lesions have subsequently been shown to be KSHV-infected

Pathogenesis: KSHV infection

a lytic and latent infection in endothelial cells,

both of which are probably important in KS pathogenesis

Cytokines and VEGF production

Cellular proliferation and prevent apoptosis by viral production of p53 inhibitors and a viral homologue of cyclin D.

MorphologyPATCH, PLAQUE, NODULE

Patches - red to purple macules

typically confined to the distal lower extremities

-Histology shows only dilated irregular endothelial cell–lined vascular spaces with interspersed lymphocytes, plasma cells, and macrophages (sometimes containing hemosiderin)

Raised Plaques -Composed of dermal accumulations of

dilated, jagged vascular channels lined and surrounded by plump spindle cells. -Scattered between the vascular channels are extravasated red cells, hemosiderin-laden macrophages, and other mononuclear inflammatory cells.

Nodules These lesions are composed of

sheets of plump, proliferating spindle cells, mostly in the dermis or subcutaneous tissues encompassing small vessels and slitlike spaces containing red cells.

More marked hemorrhage, hemosiderin pigment, and mononuclear inflammation is present; mitotic figures are common, as are round, pink, cytoplasmic globules of uncertain nature.

The nodular stage has nodal and visceral involvement seen in African and AIDS-associated variants

MALIGNANT TUMORS Angiosarcoma

Hemangiopericytoma

Angiosarcomas Malignant endothelial neoplasms with

histology varying from well-differentiated tumors that resemble hemangiomas (hemangiosarcoma) to anaplastic lesions difficult to distinguish from carcinomas or melanomas

Often involve skin, soft tissue, breast, and liver.

Hepatic angiosarcomas are associated with carcinogen exposures:

Arsenic, Thorotrast (a radioactive contrast agent formerly used for radiologic imaging), and polyvinyl chloride

begin as deceptively small, sharply demarcated, asymptomatic, often multiple red nodules; most eventually become large, fleshy masses of red-tan to gray-white tissue . The margins blend imperceptibly with surrounding structures. Central areas of necrosis and hemorrhage are frequent

all degrees of differentiation can be seen, from plump, anaplastic but recognizable endothelial cells producing vascular channels to wildly undifferentiated tumors with a solid spindle cell appearance and without definite blood vessels

Hemangiopericytomas

Derived from pericytes—myofibroblast-like cells that are normally arranged around capillaries and venules.

Can occur as slowly enlarging, painless masses at any anatomic site,

most common on the lower extremities (especially the thigh) and in the retroperitoneum.

They consist of numerous branching capillary channels and gaping sinusoidal spaces enclosed within nests of spindle-shaped to round cells.

Special stains confirm that these cells are outside the endothelial cell basement membrane and are therefore pericytes

Pathology of Vascular Interventions

ANGIOPLASTY AND ENDOVASCULAR STENTS

Various injuries can induce an intimal hyperplastic response

Trauma caused by vascular interventions tends to induce a concentric intimal thickening composed of recruited smooth muscle cells and their associated matrix deposition.

VASCULAR REPLACEMENT

Grafts thrombosis or late intimal hyperplasia, primarily at the junction of the graft with the native vasculature

long-term patency of saphenous vein grafts is only 50% at 10 years;

90% patency for internal mammary artery

Banaay’s

Acraman Macadaag