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Diagnostic Approach to Vascular Anomalies

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Diagnostic Approach to Vascular Anomalies Diagnostic Approach to Vascular Anomalies Eulalia Baselga Hospital de la Santa Creu i Sant Pau/ Hospital San Joan de Deu Barcelona SPAIN 30 min ESPD2019 DISCLOSURES Speaker for : PI for: Isdin Novartis Almirall Pierre Fabre ▹ Pierre Fabre Polichem ▹ MSD Bioderma ▹ Leti Pfizer ▹ LEO pharma Lilly ▹ Ferrer Sanofi ▹ Mylan Founder: ▹ Sanofi ▹ Venthera ▹ [email protected]▹ 1ST STEP IS IT VASCULAR? NO YES 2nd STEP VASCULAR TUMOR VASCULAR MALFORMATION 3rd STEP INFANTILE H ANOTHER T CAPILLARY VENOUS/GVM LYMPHATIC AV COMPLEX SALMON P UNIFOCAL MICROCYSTIC th 4 STEP PWS MULTIFOCAL MACROCYSTIC CMTC FAMILIAL GLA GORHAM RETICULATED NOT FAMILIAL GEOGRAPHIC LYMPHEDEMA “RASA TYPE” 5th STEP WORK-UP 1st STEP: IS IT VASCULAR? Conditions Masquerading as hemangiomas Fibrosarcoma Rhabdomyosarcoma ▹ Neuroblastoma ▹ BIOPSY! Leukemia cutis ▹ Encephalocele ? ▹ Pilomatrixoma ▹ JXG ▹ LCH ▹ Frieden▹ et al. Austral J Dermatol 2009; 50; 77 Mulliken et al.; ISSVA VASCULAR VASCULAR TUMORS MALFORMATIONS More rapid Proliferative Very slow and progressive lesions changes Histologically “tumoral” Histologically hamartomatous VASCULAR TUMORS OR VASCULAR MALFORMATION A B C Precursor RICH Deep Hemangiomas Lesions May look like May look like venous May look like CM predominant Malformations lesion BRBNS 3rd Step: WHICH VASCULAR TUMOR Vascular tumors, ISSVA 2014 Hemangioma of infancy Hobnail hemangioma Microvenular hemangioma Congenital hemangioma Anastomosing hemangioma Benign ▹ RICH;NICH;PICH ▹ Glomeruloid hemangioma Tufted angioma ▹ Papillary hemangioma ▹ ▸ ▹ Intravascular papillary endothelial Spindle-cell hemangioma ▹ hyperplasia Epithelioid hemangioma ▹ Cutaneous epithelioid angiomatous nodule ▹ ▹ Acquired elastotic hemangioma ▹ Pyogenic granuloma Littoral cell hemangioma of the spleen ▹ ▹ Kaposiform hemangioendothelioma▹ Papillary intralymphatic ▹ Retiform hemangioendothelioma ▹ angioendothelioma (PILA), Dabska tumor Pseudomyogenic hemangioendothelioma Locally Composite hemangioendothelioma ▹ ▹ Polymorphous hemangioendothelioma agressive Kaposi sarcoma ▹ Hemangioendothelioma not otherwise ▹ ▹ specified ▹ ▹ Angiosarcoma ▹ Malignant Epithelioid hemangioendothelioma ▹ ▹ Vascular tumors, ISSVA 2014 Hemangioma of infancy Hobnail hemangioma Congenital hemangioma Microvenular hemangioma Benign Anastomosing hemangioma ▹ RICH;NICH;PICH ▹ Glomeruloid hemangioma Tufted angioma ▹ Papillary hemangioma ▹ ▸ ▹ Intravascular papillary endothelial Spindle-cell hemangioma ▹ hyperplasia ▹ Epithelioid hemangioma ▹ Cutaneous epithelioid angiomatous nodule ▹ Acquired elastotic hemangioma ▹ Pyogenic granuloma Littoral cell hemangioma of the spleen ▹ ▹ Kaposiform hemangioendothelioma ▹ Papillary intralymphatic ▹ Retiform hemangioendothelioma ▹ angioendothelioma (PILA), Dabska tumor Pseudomyogenic hemangioendothelioma Locally Composite hemangioendothelioma ▹ ▹ Polymorphous hemangioendothelioma agressive Kaposi sarcoma ▹ Hemangioendothelioma not otherwise ▹ ▹ specified ▹ ▹ Angiosarcoma ▹ Malignant Epithelioid hemangioendothelioma ▹ ▹ 3rd Step: WHICH VASCULAR MALFORMATION? Capillary M Lymphatic M AV M Venous or GVM Combined/Mixed Malformation CLV CV CL 4th Step: Which SUBTYPE of vascular malformation Capillary malformation or Vascular stain : Which one? Different recognizable phenotypes under the generic “capillary malformation “ There is more than “port-wine” Prognosis and work-up is different “Solid” capillary malf , PWS Somatic GNAQ p183 mutatio “Reticulated” , “ blotchy” , less saturated in color” cm PIK3CA;GNA11;PTPN11… Geographic; “deeply saturated” in color PIK3CA, GNAQ.. “lower lip” capillary malformation PIK3CA “RASA-1 Type” RASA1; EPHB4 CMAVM vascular stains “PRE- AV” stains MAPK:RASA1; EPHB4 CMTC 5 th Work-up for Vascular Tumors Infantile hemangioma PHACEs Syndrome 20-30% (OMIM 606519) • Posterior fossa malformation • Large segmental Facial Hemangioma • Arterial anomalies 91% • Cardiac and Coartation 45% • Eye anomalies • Sternal raphe 90% of pt with Phace: > 1 Pediatrics 2001 139:117-23 extracutaneous manifestation Arch Dermatol 1996;132:307-1 British J Dermatol 2005;153:1053 • 5 pt with thoracic / arm hemangiomas • Tortuosity of CNS vessels • Abnormal subclavian or aortic artery J Pediatr. 2016 Nov;178:24-33. Initial Work up for PHACE MRI with gadolinium and MRA head ▹ and neck Echocardiogram ▹ Ophthalmologic exam ▹ Hearing test if postnatal screening ▹ has not been done Growth curve check-up ▹ IF beard area, check airway ▹ Pelvis/Sacral/Lumbar Syndrome • Dysraphism 50% • Abnormal genitalia • Renal abnormalities Arch Derm 2006; 884. Dermatology 2007; 40 Segmental HI Lumbosacral Check for genital abnormalities ▹ < 3 m Ultrasound spine, renal, ▹ abdomen, pelvis > 3 m : Spinal, abdominopelvic MRI ▹ Multifocal Hemangiomas 16% children with more than 5 IH have hepatic hemangiomas. ▹ Usually asymptomatic when screened by ultrasound ▹ When screened usually detected earlier and better prognosis ▹ If diffuse hepatic hemangiomas: Check for hypothyroidism ▹ Pediatr Dermatol. 2011 28:245-53. Pediatr Dermatol 2015;32:808 5th Step: Work-Up for Vascular malformations Capillary M or Vascular stains PWS on face ( GNAQ 183) SWS 10-15% - Leptomeningeal angiomatosis and/or - Glaucoma R. Waelchli et al. New vascular classification of port wine stains: improving prediction of Sturge- Weber risk. BJD 2014, Oct;171(4):861-7 R. Waelchli et al. New vascular classification of port wine stains: improving prediction of Sturge-Weber risk. BJD 2014;171:861-7 GNAQ p183 mutation A prospective study of risk for Sturge-Weber syndrome in children with upper facial port-wine stain 0% 20% 0% Prospective study ▹ 66 pt < 1 y.o with ▹ PWS affecting frontal area 7% 47% 27% MRI to all, under ▹ 1y.o 11/66 (16%) had ▹ SWS Dutkiewicz et al. J Am Acad Dermatol. 2015;72:473-80 • Prospective study • 66 pt < 1 y.o with PWS affecting frontal area • MRI to all, under 1y.o 11/66 had leptomeningeal angiomatosis Distribution in these 11 pt with SWS Dutkiewicz et al. J Am Acad Dermatol. 2015;72:473-80 Zallmann M. Retrospective review of screening for Sturge- Weber syndrome with brain magnetic resonance imaging and electroencephalography in infants with high-risk port- wine stains Retrospective review 32 children at risk SWS ▹ ( frontal area afected) MRI in 14/32 ▹ Positive imaging in 11, and false negative in 3 In false negatives mri was done 4 d,7 wk and 8 wk, very ▹ early ▸ Deep venous anomaly ( highly predictive of epilepsy) PPV▸ 100%; NPV 77% ▹ Somatic Mutation in PIK3CA Cloves MCAP PIK3CA Klippel-trenaunay CLAPO P ik3Ca- PTEN hamartoma Sd PTEN (Cowden/BRRS/Solamen) elated Proteus R AKT O vergrow S mTORpectrum Cell growth, Proliferation, Angiogenesis Where in the gene is the mutation/Degr ee of cell cycle acivation Other Genetic Modifiers/epig enetics What cell lineages are affected PHENOTYPE When during embryogenesis Number of the mutation cells affected occured GENOTYPING-PHENOTYPE correlation of Vascular stains and overgrowth • Multi-institutional study-20 sites • Vascular lesion + discrepancy of growth • Wide phenotypic spectrum • 314 patients enrolled • 160 affected tissue samples • Fresh frozen • Paraffin embedded • 112 sequenced (57 published*) (NGS, hybrid capture) *J Invest Dermatol. 2018 Apr;138(4):957-967. RESULTS PIK3CA (30) ▹ GNAQ (12) ▹ GNA11 (7) ▹ PIK3R1 (7) ▹ RASA1 (2) ▹ MAP2K1 (1) ▹ PTPN11 (1) ▹ Work-up for vascular stains associated with overgrowth Lower Extremities • Check for scoliosis, need to correction Macrocephaly • Cranial MR Dilated veins or venous • D- dimer/ fibrinogen component • Consider LMWH at risk Spinal involvement • Xray if scoliosis lipomas, AVM, • MR trunk Cancer risk (Wilms tumor ?, • Repeted Renal US until 8 years (Cloves and Proteus, other??) others?) WORK-UP for Venous malformations Coagulations studies: D-Dimers ▹ Fibrinogen ▸ Risk▸ DVT ▹ Internal Involvement ▹ WORK-UP for Lymphatic malformations Localized ▹ Generalized Bones afected or not ▹ ▸ Work-up for arteriovenous malformation 1ST STEP IS IT VASCULAR? NO YES 2nd STEP VASCULAR TUMOR VASCULAR MALFORMATION 3rd STEP INFANTILE H ANOTHER T CAPILLARY VENOUS/GVM LYMPHATIC AV COMPLEX SALMON P UNIFOCAL MICROCYSTIC th 4 STEP PWS MULTIFOCAL MACROCYSTIC CMTC FAMILIAL GLA GORHAM RETICULATED NOT FAMILIAL GEOGRAPHIC LYMPHEDEMA “RASA TYPE” 5th STEP WORK-UP.
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