Transcript Vascular Malformations and Tumours

Vascular
Anomalies:
Introduction
Dr Lip Teh
Famous Mark
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History
• Jacob and peeled tree branches
• Spartan wives and beautiful statues
• Imaginatio gravidarum - maternal cravings
for fruit or maternal dreams, frights, and
fantasies (Shakespeare, Pare, Montaigne)
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James Blondel
1727
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History
• Hunter (1754) – no communication
between maternal and fetal circulation
• Dugas (1866) – no neural connections
between uterus and fetus
• Fisher (1870) - defects in embryologic
development.
• Shaw (1981) – 25% of Welsh women
believed in maternal impressions
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Classification
• Virchow (1863) – angiomas
– simplex, cavernosum, or racemosum
• Wegner (1877) – lymphagiomas
– Simplex, cavernosum, cystoides
• Confusing nomenclatures = misdiagnosis
and mistreatment
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History
• Mulliken and Glowacki (1982)
– Clinical and histologic classification
– Endothelial characteristics
– Hemangiomas and Vascular Malformations
– Validated by radiographic and biochemical
studies
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Mulliken Classification
• Vascular tumors
– Hemangioma
– Pyogenic granuloma
– kaposiform hemangioendothelioma
• Vascular malformations
– Low flow
• Capillary, Venous, lymphatic, mixed
– High flow
• Arteriovenous malformations/fistulas
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Pathogenesis: Hemangiomas
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Pathogenesis: Hemangioma
• Vasculogenesis
• 1) Intrinsic
– Mutation in a gene regulating angiogenesis
– Placental endothelial cell implantation
• 2) Extrinsic
– Growth response to factors secreted by
neighbouring cells
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Pathogenesis: Hemangioma
• proliferating phase
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endothelial hyperplasia with incorporation of [3H]thymidine
proliferation markers - alkaline phosphatase, and factor VIII
multilaminated basement membrane
clinical history of rapid growth during early infancy.
increased number of mast cells
• involuting phase
– 1) histologic fibrosis and fat deposition
– 2) low to absent [3H]thymidine labeling of endothelial cells
– 3) remaining vessels dilate
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Pathogenesis: Hemangioma
• proliferative phase
– angiogenesis factors increase.
• basic fibroblast growth factor, vascular endothelial cell
growth factor, matrix metalloproteinases, proliferating cell
nuclear antigen, E-selectin, and type IV collagenase.
• Involutional phase
– factors decrease with the onset of involution
– Urinary levels of basic fibroblast growth factor can be
monitored to assess the efficacy of treatment.
– abnormal levels of angiogenic inhibitors ie TIMP 1
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Hemangioma: Role of Mast Cells
PRS. 113(3):999-1011, March 2004 Tan, Swee T.
• hemopoietic stem cells
• Role in
– angiogenesis
• Highest numbers in proliferating phase
• FGF2, VEGF, heparin, type VIII collagen, tryptase,
chymase, histamine
– Involution
• Transgranulation (cell-cell adhesion with
macrophages and fibroblasts)
• IFN-α, IFN-β, IFN-γ, and TGF-β, clusterin/
apolipoprotein J
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Pathogenesis: Malformations
• abnormal, often combined, capillary,
arterial, venous, and lymphatic vascular
elements
• normal ultrastructural characteristics
– flat, quiescent endothelium
– normal, single-layer basement membranes
• no thymidine incorporation
• normal mast cell concentrations
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Pathogenesis: Malformations
• Errors of morphogenesis
– failure of regression of arteriovenous channels
in the primitive retiform plexus.
– Aplasia/hypoplasia
– Abnormal haemodynamics
– local ischemia
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Clinical Presentation
• Malformations
• Hemangiomas
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10-12% Caucasian
F>M 2-5x
Appears first 2 months
Involutes
Visual/airway/auditory
obstruction, ulceration,
bleeding, CHF, skeletal
distortion
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1-4%
M=F
Present at birth
Grows with age
Limb under and
overgrowth,
hyperhidrosis,bleeding,
ulceration, CHF
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Associations: Hemangioma
• Kasabach-Merritt Syndrome
• Diffuse Neonatal Hemangioma
– Visceral hemangiomas
• Benign Neonatal Hemangiomatosis
– Intracranial and facial hemangiomas
• Cobb Syndrome
– Lumbosacral hemangiomas with underlying spinal
angiomas
• Maffucci's Syndrome
– Hemangiomas and enchondromas
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Associations: Malformations
• Klippel-Trenaunay-Weber syndrome
– Limb hypertrophy, venous insufficiency
• Blue Rubber Bleb Nevus Syndrome
– GI malformations
• Sturge-Weber syndrome
• von Hippel-Lindau disease
– Retinal/optic vessels
• Osler-Weber-Rendu disease
– GI telangiectasias
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