Modern Classification and Classification of Vascular Nomenclature of Vascular Lesions

■ Accurate diagnosis is crucial for appropriate evaluation and management, which often requires multidisciplinary specialists

William P. Dillon, MD UCSF Pediatrics 2015

Classification: International Society for the International Society for the Study of Vascular Anomalies Study of Vascular Anomalies 2018 2018 Vascular ANOMALIES

Vascular Vascular MALFORMATIONS

Tumors vs Malformations Flow characteristics Genetics/ Syndromes

http://www.issva.org/UserFiles/file/ISSVA-Classification-2018.pdf VASCULAR ANOMALIES VASCULAR ANOMALIES

Vascular NEOPLASMS Vascular MALFORMATIONS Vascular NEOPLASMS Vascular MALFORMATIONS

Locally Aggressive Malignant Benign Malignant Benign Locally Aggressive

Kaposiform Infantile Retiform hemangioendothelioma Angiosarcoma Infantile hemangioma Kaposiform hemangioendothelioma Retiform hemangioendothelioma Others* Congenital hemangioma Composite hemangioendothelioma Others* Congenital hemangioma (RICH/ NICH/ PICH) Kaposi Sarcoma (RICH/ NICH/ PICH) Composite hemangioendothelioma Tufted Papillary Intralymphatic Angioendothelioma Kaposi Sarcoma Papillary Intralymphatic Angioendothelioma Spindle cell hemagioma Polymorphous hemangioendothelioma Spindle cell hemagioma Pseudomyogenic hemangioendothelioma Epitheloid hemangioma Epitheloid hemangioma Pyogenic granuloma Others Others

* Epithelioid Hemangioendothelioma * Epithelioid Hemangioendothelioma

VASCULAR ANOMALIES

Vascular Vascular NEOPLASMS MALFORMATIONS

Evolution scheme of untreated infantile hemangioma, RICH, and NICH Low-Flow High Flow

IH appears after birth, grows until the end of the first year of life, then stabilizes and gradually involutes most significantly during years 1 to 2 and continues to improve over Capillary malformation AVM the ensuing years. Venous malformation AVF Congenital are fully grown at birth and rapidly involute (RICH) or persist Lymphatic malformation Mixed indefinitely (NICH). Mixed malformation Combined Mulliken JB and Enjolras O. J Am Acad Dermatol. 2004;50(6):875–882 CVM, CLM LVM, CLVM NICH, non-involuting congenital hemangioma; RICH, rapidly involuting congenital CAVM hemangioma. The Y axis show relative size. CLAVM

VASCULAR ANOMALIES Vascular ANOMALIES

Vascular Vascular Vascular Vascular NEOPLASMS MALFORMATIONS NEOPLASMS MALFORMATIONS

Low – Flow High-Flow Low-Flow High Flow Capillary Malformation AVM Venous Malformation AVF Capillary malformation AVM Lymphatic Malformation Mixed Venous malformation AVF Mixed Malformation Lymphatic malformation Mixed Mixed malformation Combined Combined CVM, CLM CVM, CLM www.hopkinsmedicine.org LVM, CLVM LVM, CLVM CAVM CAVM CLAVM CLAVM 5 Most Common Vascular Anomalies in Head and Neck Genetics of Vascular Lesions

■ Most vascular anomalies occur sporadically, but several genes and genetic disorders have been identified

■ Infantile hemangioma ■ Five categories of vascular anomalies with patterned ■ Capillary malformation (port wine stains) inheritance include: – Capillary malformation (RASA-1) ■ Lymphatic malformation – CM-Arteriovenous malformation (RASA-1) ■ Venous malformation – Lymphatic malformation (VEGFR3) – Venous malformation (TIE2/TEK) ■ Arteriovenous malformation – Infantile hemangioma (atopy and familial clustering) » erythrocyte-type glucose transporter protein GLUT1 + (all phases)

■ Syndromes associated with Capillary Malformations – Sturge-Weber, Klippel-Trenaunay and Parkes Weber Syndromes

RASA 1 Mutation Congenital vs. Infantile Hemangiomas ■ RASA 1 is involved in signaling for growth factors involved in proliferation, migration and survival of cell Congenital Hemangioma Infantile Hemangioma types, including vascular endothelial cells ■ Less common ( not rare) ■ Common 5% of newborns ■ Present at birth/ US ■ Visible by 2 wks-4 months ■ Associated with multiple hereditary capillary ■ Growth complete or slow ■ Grows rapidly for ~8 malformations (CM) with or without AVM, AVF or Parkes months Weber syndrome. MRI screening of patients with CMs ■ may be indicated to detect spinal or intracranial AVMS ■ M=F F (5) >>M (1) ■ ■ Involution variable Slow involution over months to years ■ Mutation is accompanied at various points of – Rapid (RICH) development of the fetus or child by second mutations – Non Involuting ( NICH) on the second allele of the same gene in the dividing – Partial involuting (PICH) cells: thus variation in location and timing ■ GLUT 1 negative ■ Glut 1 positive

Hemangioma vs

Infantile Hemangioma Vascular Malformation

Age Infancy & childhood All ages

Time course Proliferation, then regression Slow progression

Sex prevalence 3-9 F:M 1:1 F:M

Cellular features High endothelial cell turnover Normal cell turnover

Immunomarkers VEGF, bFGF, Glut 1+ VEGF, bFGF-, Glut 1 -

Factors causing None known Trauma, infection, hormonal flares

GLUT1 = erythrocyte-type glucose transporter protein Thank you !!