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The Classification of Capillary Malformations

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The Classification of Capillary Malformations The classification of capillary malformations Dubrovnik 3 May 2019 Rudolf Happle Department of Dermatology University of Freiburg Germany Background:: The unsuitable classification of the International Society for the Study of Vascular Anomalies (ISSVA) The unsuitable classification of the ISSVA Capillary malformation Capillary malformation Capillary malformation Capillary malformation Capillary malformation Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies Wassef M et al and ISSVA Board and Scientific Committee: Pediatrics 2015 Klippel-Trenaunay syndrome: CM + VM +/− LM + limb overgrowth Parkes-Weber syndrome: CM + AVF + limb overgrowth Servelle-Martorell syndrome: limb VM + bone undergrowth Sturge-Weber syndrome: facial + leptomeningeal CM + ocular anomalies +/− bone and/or soft tissue overgrowth Limb CM + congenital nonprogressive limb hypertrophy Maffucci syndrome: VM +/− spindle cell hemangioma + enchondroma Macrocephaly-CM (M-CM)/megalencephaly-CM-polymicrogyria (MCAP) Microcephaly-CM (MICCAP) CLOVES syndrome: LM + VM + CM +/− AVM + lipomatous overgrowth Proteus syndrome: CM, VM and/or LM + asymmetric somatic overgrowth Bannayan-Riley-Ruvalcaba syndrome: AVM + VM + macrocephaly, lipomatous overgrowth Approved in Amsterdam, May 2018 For pediatric dermatologists, this classification is useless! http://www.issva.org/classification All of these capillary nevi may occur without any extracutaneous abnormality! Nevus flammeus Nevus roseus Rhodoid nevus Nevus vascularis mixtus Segmental angioma serpiginosum 1 Nevus flammeus 1 Nevus flammeus GNAQ Shirley MD et al: N Engl J Med 2013 Nevus flammeus and Sturge-Weber syndrome are G-protein disorders G proteins control the cellular signal transduction Do facial nevi flammei reflect the trigeminal innervation? No! Do facial nevi flammei reflect the trigeminal innervation? Authors who still believe Authors who argue in this concept against the concept Most authors of chapters Alexander GL: Handbook of in textbooks Clinical Neurology 1972 Happle R: Exp Dermatol 2006 Happle R: Mosaicism in Human Skin 2014 Dutkiewicz AS et al: J Am Acad Dermatol 2015 Apparently, nevus flammeus is arranged in a flag-like (checkerboard) pattern Tomi Ungerer (1931-2019) Torchia D et al: Vissers W et al: Int J Dermatol 2013 Eur J Dermatol 2003 Epilepsy surgery in Sturge-Weber syndrome Epilepsy surgery in Sturge-Weber syndrome: Lobotomy of a posterior quadrant is preferable to lobectomy 8/10 patients became free from seizures Postoperative MRI Line of disconnection: Scheme of disconnection Sugano H et al: Epilepsia 2014 Thomas SG et al: Int J Pediatr 2012 Hemispherotomy is preferable to hemispherectomy Axial scan one year after hemispherotomy Giordano F et al: Childs Nerv Syst 2015 Liu X et al: SpringerPlus 2016 De Palma L et al: Epilepsy Behav 2019 2 Port-wine nevus of the Proteus type AKT1 Thanks to Dr. Sigrid Tinschert, Berlin, Germany 2 3 Port-wine nevus Port-wine nevus of the Proteus type of the CLOVES type AKT1 PIK3CA Thanks to Gucev ZS et al: Dr. Sigrid Tinschert, Am J Med Genet part A Berlin, Germany 2008 4 Nevus roseus Nevus flammeus versus Nevus roseus Thanks to the late Dr. Urs W. Schnyder, Zurich Happle R: Eur J Dermatol 2005 Phacomatosis spilorosea: Macular nevus spilus combined with a nevus roseus (and never with a nevus flammeus!) Jordaan HF, Happle R: Happle R: Fink C et al: Br J Dermatol 2008 J Eur Acad Dermatol Venereol J Eur Acad Dermatol Venereol 2015 2016 Phacomatosis cesioflammea Phacomatosis spilorosea GNAQ PTPN11* GNA11 * Will be presented tomorrow Thomas AC et al: by Dr. Satyamaanasa Polubothu J Invest Dermatol 2016 at 8:30 hrs in Elafiti Hall II ! 5 6 Cutis marmorata Reticular capillary telangiectatica congenita nevus Cause is unknown, so far Postzygotic PIK3CA mutation Rivière JB et al: Nat Genet 2012 PROS (PIK3CA-Related Overgrowth Spectrum) Reticular capillary nevus- megalencephaly syndrome („M-CAP“) Megalencephaly Polymicrogyria Ventriculomegaly Mirzaa GM et al: Am J Med Genet 2012 Reticular capillary nevus Gonzalez ME et al: Lee MS et al: Pediatr Dermatol 2009 J Am Acad Dermatol 2013 7 8 9 Nevus Nevus vascularis Angiokeratoma anemicus mixtus circumscriptum ? ? Hamm H, Happle R: Hautarzt 1986 10 Rhodoid nevus RASA1 (Eerola et al. 2003) EPHB4 (Yu et al. 2017; Amyere M et al. 2017) Thanks to Dr. Regina Fölster-Holst, Thanks to Dr. Antonio Torrelo, Thanks to Kiel, Germany Madrid, Spain Dr. Cornelia Seitz, Göttingen, Germany 10 Rhodoid nevus RASA1 (Eerola et al. 2003) EPHB4 (Yu et al. 2017; Amyere M et al. 2017) Thanks to Dr. Regina Fölster-Holst, Thanks to Dr. Antonio Torrelo, Kiel, Germany Madrid, Spain In this autosomal dominant trait, AVM is a type 2 segmental manifestation that occurs rather rarely. Gandon C et al: Hence, „CM-AVM“ is a misleading term. Pediatr Dermatol 2016 11 12 Segmental angioma serpiginosum Midfacial port-wine stain of the PROS type ? Chen WC et al: Dermatology 2006 Krämer D et al: Int J Dermatol 2016 13 14 15 Unilateral punctate Unilateral nevoid Carter-Mirzaa macules telangiectasia telangiectasia, patchy type STAMPB Grimaldi M et al: ? McDonell LM et al: Nat Genet 2013 ? Acta Derm Venereol 2001 Capillary non-nevi Capillary non-nevi 16 17 18 Autosomal dominant Teleangiectasia Fabry disease angiokeratoma corporis diffusum haemorrhagica hereditaria ENG; GLA ? HHT2; ALK1 Zampetti A et al: Calzavara-Pinton PG et al: Bedford J et al: Br J Dermatol 2012 Arch Dermatol 1995 N Z Med J 2013 19 Hereditary angioma serpiginosum Marriott PT et al: Br J Dermatol 1975 ? Capillary non-nevi 20 Salmon patch „Unna‘s nevus“ „Nevus simplex“ „Median nevus flammeus“ Juern AM et al: J Am Acad Dermatol 2010 20 different capillary malformations Capillary nevi • Naevus flammeus • Carter-Mirzaa macules • Port-wine nevus of the Proteus type • Unilateral punctate telangiectasia • Port-wine nevus of the CLOVES type • Unilateral nevoid telangiectasia, patchy type (PROS) • Nevus roseus • Cutis marmorata telangiectatica • Reticular capillary nevus (PROS) Capillary non-nevi • Nevus anemicus • Salmon patch • Nevus vascularis mixtus • Rendu-Osler disease • Angiokeratoma circumscriptum • Fabry disease • Rhodoid nevus • Autosomal dominant angiokeratoma • Segmental angioma serpiginosum corporis diffusum • Hereditary angioma serpiginosum • Midfacial port-wine patch (PROS) 20 different capillary malformations Capillary nevi • Naevus flammeus • Carter-Mirzaa macules • Port-wine nevus of the Proteus type • Unilateral punctate telangiectasia • Port-wine nevus of the CLOVES type • Unilateral nevoid telangiectasia, patchy type (PROS) • Nevus roseus • Cutis marmorata telangiectatica • Reticular capillary nevus (PROS) Capillary non-nevi • Nevus anemicus • Salmon patch • Nevus vascularis mixtus • Rendu-Osler disease • Angiokeratoma circumscriptum • Fabry disease • Rhodoid nevus • Autosomal dominant angiokeratoma • Segmental angioma serpiginosum corporis diffusum • Hereditary angioma serpiginosum • Midfacial port-wine patch (PROS) 20 different capillary malformations Capillary nevi • Naevus flammeus • Carter-Mirzaa macules • Port-wine nevus of the Proteus type • Unilateral punctate telangiectasia • Port-wine nevus of the CLOVES type • Unilateral nevoid telangiectasia, patchy type (PROS) • Nevus roseus • Cutis marmorata telangiectatica • Reticular capillary nevus (PROS) Capillary non-nevi • Nevus anemicus • Salmon patch • Nevus vascularis mixtus • Rendu-Osler disease • Angiokeratoma circumscriptum • Fabry disease • Rhodoid nevus • Autosomal dominant angiokeratoma • Segmental angioma serpiginosum corporis diffusum • Hereditary angioma serpiginosum • Midfacial port-wine patch (PROS) 20 different capillary malformations Capillary nevi • Naevus flammeus • Carter-Mirzaa macules • Port-wine nevus of the Proteus type • Unilateral punctate telangiectasia • Port-wine nevus of the CLOVES type • Unilateral nevoid telangiectasia, patchy type (PROS) • Nevus roseus • Cutis marmorata telangiectatica • Reticular capillary nevus (PROS) Capillary non-nevi • Nevus anemicus • Salmon patch • Nevus vascularis mixtus • Rendu-Osler disease • Angiokeratoma circumscriptum • Fabry disease • Rhodoid nevus • Autosomal dominant angiokeratoma • Segmental angioma serpiginosum corporis diffusum • Hereditary angioma serpiginosum • Midfacial port-wine patch (PROS) 20 different capillary malformations Capillary nevi • Naevus flammeus • Carter-Mirzaa macules • Port-wine nevus of the Proteus type • Unilateral punctate telangiectasia • Port-wine nevus of the CLOVES type • Unilateral nevoid telangiectasia, patchy type (PROS) • Nevus roseus • Cutis marmorata telangiectatica • Reticular capillary nevus (PROS) Capillary non-nevi • Nevus anemicus • Salmon patch • Nevus vascularis mixtus • Rendu-Osler disease • Angiokeratoma circumscriptum • Fabry disease • Rhodoid nevus • Autosomal dominant angiokeratoma • Segmental angioma serpiginosum corporis diffusum • Hereditary angioma serpiginosum • Midfacial port-wine patch (PROS) Different capillary nevi: Rhodoid nevus Nevus flammeus Nevus roseus „Capillary malformation“ Nevus vascularis Nevus anemicus mixtus is an Port-wine nevus asylum ignorantiae of the CLOVES type Reticular Happle R: J Eur Acad Dermatol Venereol 2015 capillary nevus Port-wine nevus Cutis marmorata Angiokeratoma Segmental angioma telangiectatica congenita of the Proteus type circumscriptum serpiginosum Thank you! .
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