Aneurysms & Vascular Tumors PDF

I- Aneurysms and Dissections II- Tumors of Blood Vessels Dr. Abdul Rehman Department of Pathology  Learning Outcomes Define and classify aneurysms Compare the pathogenesis, morphology and complications of abdominal aortic aneurysm, thoracic aortic an...

I- Aneurysms and Dissections II- Tumors of Blood Vessels Dr. Abdul Rehman Department of Pathology  Learning Outcomes Define and classify aneurysms Compare the pathogenesis, morphology and complications of abdominal aortic aneurysm, thoracic aortic aneurysm and aortic dissection Classify the tumors of blood vessels Elaborate the clinical features and morphology of hemangiomas, lymphangiomas, kaposi sarcoma and angiosarcoma  Aneurysms And Dissections Connectivetissuedialation Definition: “Congenital or acquired dilations of blood vessels or the heart” Localized, abnormal and irreversible True aneurysm: all threelayers are dilated G– All three layers of artery or attenuated wall of heart – Atherosclerotic, congenital vascular aneurysms & TF EE.FIventricular aneurysms resulting from transmural MI TE IntieE m.es n o o iti.mn  ay fusiform False aneurysm (pseudoaneurysm): – A wall defect leads to the formation of extravascular hematoma 1 – Ventricular ruptures by pericardial adhesions Aneurysms can be classified by shape: Saccular aneurysms: – Discrete outpouchings ranging from 5 to 20 cm dia – Often with a contained thrombus Fusiform aneurysms: dialationinbei.de EeitT1t 9meene – Circumferential dilations up to 20 cm in diameter – Involve aortic arch, abdominal aorta & iliac arteries Arterial Dissection: arises when pressurized blood enters the arterial wall through a surface defect and pushes apart the underlying layers (dissecting between its layers)  Aneurysms and dissections are important causes of stasis and subsequent thrombosis Propensity to rupture, often with catastrophic results Pathogenesis of Aneurysm: is notthere Occur when structural integrity of aortic media is compromised due to an imbalance between the hanger synthesis and degradation of the ECM 1. Inadequate or abnormal connective tissue synthesis extracellur matrix Mutations in TGF-β receptors or downstream signaling pathways  defective elastin & collagen synthesis been jabnomam.is Marfan syndrome – defective synthesis of fibrillin congital Type-IV Ehlers-Danlos syndrome – defective type-III connectivetis disease collagen synthesis  ffemif.EE 2. Excessive connective tissue degradation: Increased inflammation- associated MMP (matrix metalloproteinases)  degradation of ECM in arterial wall Decreased TIMP expression  ECM degradation S 3  3. Loss of smooth muscle cells or change in smooth muscle cell synthetic phenotype: Atherosclerotic intimal thickening  ischemia of inner media Tfthelumin wincauset Systemic hypertension  narrowing of aortic vasa vasorum  ischemia of outer media Ischemia  SMC loss & aortic degenerative changes (fibrosis, inadequate ECM synthesis by SMCs & accumulation of amorphous proteoglycans) Cystic Medial Degeneration: (Histological appearance) Marfan syndrome Normal Cystic medial degeneration - Marked elastin fragmentation - Areas devoid of elastin  resemble cystic spaces  Predisposing conditions for Aortic Aneurysms he will ask about what causeAortic Agyth 1. Atherosclerosis 2. Hypertension 3. Smoking Atherosclerosis & smoking abdominal aortic aneurysms Hypertension  thoracic aortic aneurysms Other causes: – Trauma, Vasculitis, Congenital defects, Infections (mycotic aneurysms) L  1. Abdominal Aortic Aneurysm view Cause: Atherosclerosis Important in Examination point of men Risk Factors: Men, smokers, 50 years or more Pathogenesis: Altered balance of collagen degradation & synthesis mediated by local inflammatory infiltrates & destructive proteolytic enzymes Compromised diffusion – Atherosclerosis Direct compression of underlying media – ATH  degeneration & necrosis of media  arterial wall thinning  aneurysm Familial predisposition - hereditary defects in structural components of aorta (Marfan syndrome)  Morphology of AAA Location: Typically b/w renal arteries and aortic bifurcations Shape: saccular or fusiform Size: 15 cm dia, 25 cm length Lysine Extensive atherosclerosis with thinning & focal destruction of underlying media III AorticAneurysm Mural thrombus Inflammatory AAAs: Dense periaortic fibrosis containing abundant lymphoplasmacytic infiltrate with many macrophages & giant cells Mycotic AAAs: occur when circulating microorganisms seed the aneurysm wall or the associated thrombus  Clinical Consequences of AAA Obstruction of aortic branch vessel  distal ischemia Embolism of atheromatous material or mural thrombus Impingement on adjacent structures Presentation as an abdominal mass Rupture into peritoneal cavity or retroperitoneal tissues Risk of rupture  25% in larger than 6cm in diameter Surgical management – 5.5 cm or larger aneurysms  2. Thoracic Aortic Aneurysm Most commonly associated with 1. Hypertension 2. Bicuspid aortic valves 3. Marfan syndrome if 4. Disorders caused by mutations in TGF-β signaling pathway Signs & symptoms: 1. Respiratory or feeding difficulties Because compition of heaim Arah 2. Persistent cough Team.EE 3. Pain 4. Cardiac disease otisai a 5. Aortic dissection or rupture  g 3. Aortic Dissection tonicamedia The blood splays apart the laminar planes of media to form a blood-filled channel within the aortic wall Two epidemiologic age groups 1. Men aged 40 to 60 years with hypertension 2. Younger patients with connective tissue abnormalities affecting the aorta (Marfan syndrome) Iatrogenic dissections Pregnancy (rare) maybe associate with highestrogen level  Pathogenesis Hypertension  major risk factor for aortic dissection Hypertension  Narrowing of vasa vasorum with ECM degeneration & variable loss of medial SMCs  decreased blood flow through vasa vasorum Inherited or acquired connective tissue disorders that give rise to abnormal aortic ECM e.g. Marfan syndrome, Ehlers-Danlos syndrome Intimal tear – point of origin  progression of medial hematoma  Morphology: Location of intimal tear: Ascending aorta Shape of tear: Transverse or oblique Length of tear: 1-5 cm he will not ask Usually lies b/w middle & outer third of media External rupture – massive hemorrhage or cardiac tamponade Double-barreled aorta: Occasionally hematoma reenters the lumen of the aorta through a second distal intimal tear – chronic dissection Histologically: Cystic medial degeneration  Classification of Aortic Dissection Important tearted wit from away core Proximal Dissection Distal Dissection went  Clinical Features of Aortic Dissection Classic clinical symptoms  sudden onset of excruciating tearing or stabbing pain Most common cause of death is rupture of dissection into pericardial, pleural & peritoneal cavity Retrograde dissection into the aortic root can cause disruption of aortic valvular apparatus or compression of coronary arteries Common clinical manifestations:  Cardiac tamponade  Aortic insufficiency  Myocardial infarction  Extension of dissection into other arteries Tumors of Blood Vessels Distinction Between Benign and Malignant Vascular tumors Benign tumors: - Composed of well-formed vascular channels filled with blood cells or lymph that are lined by a monolayer of bland ECs Malignant tumors - More cellular, show cytologic atypia, are proliferative (increased mitotic figures) and usually do not form well-organized vessels  Benign Tumors Hemangiomas: Benign tumors composed of blood-filled vessels Mostly present from birth – expansion & regression Typically localized lesions Superficial (head & neck) & internal (liver) lesions 1. Capillary Hemangiomas: Most common type Site: skin, subcutaneous tissues, mucous membranes of oral cavities, lips, liver, spleen, and kidneys Histologically: Thin-walled capillaries with scant stroma 2. Infantile hemangiomas: Strawberry hemangiomas Newborn skin lesion Grow rapidly for a few months, begin to involute by 1 to 3 years of age & completely regress by 7 years of age in majority cases 3. Pyogenic granulomas: Capillary proliferations of uncertain etiology Manifest as rapidly growing red pedunculated lesions on the skin, gingival, or oral mucosa Bleed easily & often ulcerate Microscopically, resemble granulation tissue, proliferating capillaries with extensive edema and an acute and chronic inflammatory infiltrate  Morphology of Hemangiomas Capillary Hemangioma Pyogenic Granuloma Cavernous Hemangioma 4. Cavernous Hemangiomas: Composed of large, dilated vascular channels More infiltrative and locally destructive Frequently involve deep structures No spontaneous regression Site: Liver is common site but may affect any tissue Vulnerable to traumatic ulceration & bleeding Histology – sharply defined but unencapsulated Large blood-filled vascular spaces separated by connective tissue stroma Intravascular thrombosis with dystrophic calcification  Lymphangiomas Simple (Capillary) lymphangiomas: Slightly elevated or pedunculated lesions,1 to 2 cm in diameter that occur predominantly in head, neck, and axillary subcutaneous tissues Histologically- Networks of endothelium-lined spaces that are distinguished from capillary channels only by the absence of blood cells Cavernous lymphangiomas (Cystic hygromas): Typically found in neck, or axilla of children Common in Turner syndrome Massively dilated lymphatic spaces lined by ECs & separated by connective tissue stroma containing lymphoid aggregates Unencapsulated and indistinct margins  Glomus tumors (Glomangiomas) Benign, painful tumors Arise from specialized SMCs of glomus bodies (arteriovenous structures involved in thermoregulation) Most commonly found in distal portion of digits, especially under fingernails Bacillary Angiomatosis A rare vascular proliferation in immunocompromised patients caused by opportunistic gram –ve bacilli of Bartonella family Skin, bone, brain and other organs Intermediate-Grade (Borderline) Tumors Kaposi Sarcoma (KS): A vascular neoplasm caused by Kaposi sarcoma herpesvirus (KSHV, HHV-8) Most primary KSHV infections are asymptomatic Four forms of KS have been recognized 1. Classic KS (European KS): Older men of Mediterranean, Central and Eastern European region Multiple red-purple skin plaques or nodules, usually on the distal lower extremities  progressively increase in size and number & spread proximally Persistent, typically asymptomatic & remain localized to skin and subcutaneous tissue 2. Endemic African KS: Occurs in sub-Saharan Africa Younger under 40 years of age Indolent or aggressive course Lymph node involvement > classic variant A particularly severe form with prominent LN & visceral involvement occurs in prepubertal children Poor prognosis (100% mortality within 3 years) 3. Transplantation-associated KS: Solid-organ transplant recipients with T-cell immunosuppression Aggressive course with nodal, mucosal & visceral involvement Cutaneous lesions may be absent 4. AIDS-associated (epidemic KS): Most common HIV-related malignancy Incidence has fallen > 80%  antiretroviral therapy Involves lymph nodes & disseminates widely to viscera early in its course Majority die of opportunistic infections rather from KS Pathogenesis: All KS lesions are infected by KSHV (HHV-8) Transmission – sexual contact, oral secretions & cutaneous exposures KSHV and altered T-cell immunity Inherited variations in genes that modulate cytokine expression such as interleukin 8 receptor-beta (IL8Rβ) and interleukin 13 (IL-13) genes  Morphology of Kaposi Sarcoma In classic KS, the cutaneous lesions progress through three stages 1. Patch 2. Plaque 3.Nodule 1. Patches: Pink, red, or purple macules Typically affecting distal lower extremities 2. Plaques: With time, lesions spread proximally Become larger, violaceous, raised plaques Microscopic examination- composed of dilated, jagged dermal vascular channels lined & surrounded by plump spindle cells, hemosiderin-laden macrophages and mononuclear inflammatory cells 3. Nodules: – Composed of sheets of plump, proliferating spindle cells in the dermis or subcutaneous tissues, often with interspersed slitlike spaces – Hemorrhage & hemosiderin deposition – Numerous mitotic figures – Accompanied by nodal and visceral involvement  Malignant Tumors Angiosarcomas: Malignant endothelial neoplasms Highly differentiated  wildly anaplastic lesions Older adults without gender predilection Site (any) – skin, soft tissue, breast and liver Aggressive tumors that invade locally & metastasize Prognosis: 5-year survival rates  30% Hepatic angiosarcomas – carcinogenic exposure {Arsenical pesticides and polyvinyl chloride (PVC)} Lymphedema – lymphangiosarcoma Radiation Gross Morphology: Begin as small, sharply demarcated, asymptomatic red nodules  large, fleshy red-tan to gray-white masses with poorly defined margins Necrosis & hemorrhage Microscopic Morphology: Variable extent of differentiation ranging from plump, atypical ECs producing vascular channels to undifferentiated spindled to epithelioid cell tumors without definite blood vessels Endothelial cell origin – CD31 & ERG  Morphology of Angiosarcoma Angiosarcoma of Right Moderately differentiated IHC- CD 31 (Endothelial ventricle Angiosarcoma cell marker)  Reference (Chapter 8- Page 288-292, 300-304)