ISSVA classification for vascular anomalies

1 1 ISSVA classification for vascular anomalies (Approved at the 20th ISSVA Workshop, Melbourne, April 2014, last revision May 2018)This classification is intended to evolve as our understanding of the biology and genetics of vascular malformations and tumors continues to growOverview table defined as two or more vascular malformations found in one lesion* high-flow lesionsA list of causal genes and related vascular anomalies is available inAppendix 2 The tumor or malformation nature or precise classification of some lesions is still unclear.

2 These lesions appear in a separate provisional anomaliesVascular tumorsVascular malformationsSimpleCombined of major named vesselsassociated with other anomaliesBenignLocally aggressive or borderlineMalignantCapillary malformationsLymphatic malformationsVenous malformationsArteriovenous malformations*Arteriovenous fistula*CVM, CLMLVM, CLVMCAVM*CLAVM*othersSee detailsSee listFor more details, click on the underlined linksAbbreviations used*some lesions may be associated with thrombocytopenia and/or consumptive coagulopathy see details many experts believe that tufted angioma and kaposiform hemangioendothelioma are part of a spectrum rather than distinct proliferative vascular lesions are listed with benign tumorsISSVA classification ofvascular tumors 1aBenign vascular tumors 1 Infantile hemangioma / Hemangioma of infancysee detailsCongenital hemangiomaGNAQ / GNA11 Rapidly involuting(RICH) *Non-involuting (NICH)

3 Partially involuting(PICH)Tufted angioma * GNA14 Spindle-cell hemangiomaIDH1 / IDH2 Epithelioid hemangiomaFOSP yogenic granuloma (also known as lobular capillary hemangioma)BRAF / RAS / GNA14 Otherssee detailsBack to overviewType Alt for previous viewCausal genes in tumor nature of some of these lesions is not certainReactive proliferative vascular lesions are listed with benign tumorsISSVA classification ofvascular tumors 1bBenign vascular tumors2 OthersHobnail hemangiomaMicrovenular hemangiomaAnastomosing hemangiomaGlomeruloid hemangiomaPapillary hemangiomaIntravascular papillary endothelial hyperplasiaCutaneous epithelioid angiomatous noduleAcquired elastotic hemangiomaLittoral cell hemangioma

4 Of the spleenRelated lesionsEccrine angiomatous hamartomaReactive angioendotheliomatosisBacillary angiomatosisBack to overviewType Alt for previous viewISSVA classification ofvascular tumors 2 Locally aggressive or borderline vascular tumorsKaposiform hemangioendothelioma * GNA14 Retiform hemangioendotheliomaPapillary intralymphatic angioendothelioma (PILA), Dabska tumorComposite hemangioendotheliomaPseudomyogenichemang ioendotheliomaFOSBP olymorphous hemangioendotheliomaHemangioendothelioma not otherwise specifiedKaposi sarcomaOthersMalignant vascular tumorsAngiosarcoma(Post radiation)

5 MYCE pithelioid hemangioendothelioma CAMTA1/ TFE3 OthersBack to overview*some lesions may be associated with thrombocytopenia and/or consumptive coagulopathy see details many experts believe that tufted angioma and kaposiform hemangioendothelioma are part of a spectrum rather than distinct proliferative vascular lesions are listed with benign tumorsType Alt for previous viewCausal genes in blueSimple vascular malformations ICapillary malformations (CM)Nevus simplex / salmon patch, angel kiss , stork bite Cutaneous and/or mucosal CM (also known as port-wine stain) NonsyndromicCMGNAQCM with CNS and/or ocular anomalies (Sturge-Weber syndrome)GNAQCM with bone and/or soft tissues overgrowthGNA11 DiffuseCM with overgrowth (DCMO)GNA11 Reticulate CMCM of MIC-CAP (microcephaly- capillary malformation )STAMBPCM of MCAP (megalencephaly- capillary malformation -polymicrogyria)PIK3 CACM of CM-AVMRASA1 / EPHB4 Cutis marmorata telangiectatica congenita (CMTC)

6 OthersTelangiectasia*Hereditary hemorrhagic telangiectasia (HHT)(HHT1 ENG, HHT2 ACVRL1, HHT3, JPHTSMAD4)OthersBack to overviewType Alt for previous view* The CM nature of some subtypes of telangiectasia is debated. Some telangiectasia may be reclassified in other sections in the futureCausal genes in blueISSVA classification for vascular anomaliesSimple vascular malformations IIaLymphatic malformations (LM) Common (cystic) LM *PIK3 CAMacrocystic LMMicrocystic LMMixed cystic LMGeneralized lymphatic anomaly (GLA)Kaposiform lymphangiomatosis (KLA)LM in Gorham-Stout diseaseChannel type LM Acquired progressive lymphatic anomaly (so called acquired progressive "lymphangioma")Primary lymphedema (different types)

7 Others ISSVA classification for vascular anomaliesBack to overviewCausal genes in blueType Alt for previous view* When associated with overgrowth, some of these lesions belong to the PIK3CA-related overgrowth spectrumsee detailsSome of these lesions may be associated with thrombocytopenia and/or consumptive coagulopathy see detailsBack to overviewISSVA classification for vascular anomaliesType Alt for previous viewSimple vascular malformations IIbPrimary lymphedema Nonne-Milroy syndromeFLT4 / VEGFR3 Primary hereditary lymphedemaVEGFCP rimary hereditary lymphedemaGJC2 / Connexin 47 Lymphedema-distichiasisFOXC2 Hypotrichosis-lymphedema-telangiectasia SOX18 Primary

8 Lymphedema with myelodysplasiaGATA2 Primary generalized lymphatic anomaly (Hennekam lymphangiectasia-lymphedema syndrome)CCBE1 Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndromeKIF11 Lymphedema-choanal atresiaPTPN14 Causal genes in blueSimple vascular malformations IIIV enous malformations (VM) Common VMTEK (TIE2) / PIK3 CAFamilial VM cutaneo-mucosal (VMCM)TEK (TIE2)Blue rubber bleb nevus (Bean) syndrome VMTEK (TIE2)Glomuvenous malformation (GVM)GlomulinCerebral cavernous malformation (CCM) (CCM1 KRIT1, CCM2 Malcavernin, CCM3 PDCD10)Familial intraosseous vascular malformation (VMOS)ELMO2 Verrucous venous malformation (formerly verrucous hemangioma)MAP3K3 OthersISSVA classification for vascular anomaliesBack to overviewsome lesions may be associated with thrombocytopenia and/or consumptive coagulopathy see detailsType Alt for previous viewCausal genes in blueSimple vascular malformations IVArteriovenous malformations (AVM) SporadicMAP2K1In HHT(HHT1 ENG, HHT2 ACVRL1, HHT3, JPHTSMAD4)

9 In CM-AVMRASA1/ EPHB4 OthersArteriovenous fistula (AVF) (congenital)SporadicMAP2K1In HHT(HHT1 ENG, HHT2 ACVRL1, HHT3, JPHTSMAD4)In CM-AVMRASA1/ EPHB4 OthersISSVA classification for vascular anomaliesBack to overviewAbbreviations usedType Alt for previous viewCausal genes in blueISSVA classification for vascular anomaliesCombined vascular malformations*CM + VMcapillary-venous malformationCVMCM + LMcapillary-lymphatic malformationCLMCM + AVMcapillary-arteriovenous malformationCAVMLM + VMlymphatic-venous malformationLVMCM + LM + VMcapillary-lymphatic-venous malformationCLVMCM + LM + AVMcapillary-lymphatic-arteriovenous malformationCLAVMCM + VM +

10 AVMcapillary-venous-arteriovenous malformationCVAVMCM + LM + VM + AVMcapillary-lymphatic-venous-arterioven ous to overviewAbbreviations used* defined as two or more vascular malformations found in one lesionType Alt for previous viewISSVA classification for vascular anomaliesBack to overviewAnomalies of major named vessels(also known as "channel type" or "truncal" vascular malformations)Affectlymphaticsveinsarter iesAnomalies oforigincoursenumberlengthdiameter (aplasia, hypoplasia, stenosis, ectasia / aneurysm)valvescommunication (AVF)persistence (of embryonal vessel)Abbreviations usedType Alt for previous viewISSVA classification for vascular anomaliesBack to overviewVascular malformations associated with other anomaliesKlippel-Trenaunay syndrome: *CM + VM +/-LM + limb overgrowthPIK3 CAParkes Weber syndrome: CM + AVF + limb overgrowthRASA1 Servelle-Martorell syndrome:limb VM + bone undergrowthSturge-Weber syndrome.