Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. Abbreviations: Count: Word sclerotherapy mation, Keywords: [email protected] Room (fax) interest Drive, 919-681-7950 of Trent (phone) conflict 330 919-684-3401 No Center 27710 NC Medical Durham University House Duke Hanes Hematology/Oncology 383 Pediatric MD Pahl Kristy Radiology, of of Author: School University Corresponding Department Stanford (2) Pediatrics, of Center, Department Medical (3) Medicine Center, University Medical Duke University Duke Pediatrics, of the Department discuss to means KS a malformations Pahl vascular as localized cases Simple four Approach presents malformations. We review vascular increasingly How localized This becoming simple, of is disorders. strategies oncologist management these and and of features, hematologist imaging management and pediatric capillary, and clinical include The diagnosis, malformations diagnosis simple These the involvement. malformations. in of malformations. area arteriovenous involved single vascular a and and malformations to vascular tumors localized venous, localized are vascular that Simple, lymphatic, malformations subtypes: non-proliferative. of are distinct group a malformations two to while into refer nature, divided in proliferative disorders are of tumors Vascular group a are anomalies Vascular Abstract 2021 3, April 2 1 Pahl Kristy anomalies vascular localized approach we How tnodUiest eia Center Medical University Stanford Center Medical University Duke 1 ao-ao WM Pabon-Ramos , aclrmlomto,vnu afrain ypai afrain reivnu malfor- arteriovenous malformation, lymphatic malformation, venous malformation, vascular 1 aek Pabon-Ramos Waleska , btat 97 Abstract- , antx-4149 text- Main I aclrItretoa Radiology Interventional Vascular Phenomenon tomography Kasabach-Merritt Computerized VIR imaging resonance Magnetic KMP Ultrasound CT coagulation intravascular Localized MRI malformation Capillary US LIC malformation malformation Arteriovenous Lymphatic CM malformation AVM Venous LM VM 2 egMR Jeng , 1 n ihe Jeng Michael and , . ubro als 2 tables: of Number 3 1 2 . ubro iue:6 Figures: of Number Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. o.Lbrtr okpwssgicn o ltltcuto 7,0 nra 150,000- (normal 175,000 of count low platelet with a lesion for heterogeneous significant compressible, was a workup soft, 450,000x10 demonstrated Laboratory cm Doppler 6 flow. with x anomaly. were ultrasound cm vascular nodules or 6 An hardened sarcoma, process No a annulare), inflammatory lateral hue. lipoblastoma, granuloma exam, the such bluish near subcutaneous lesions tumors lesion physical slight fatty ankle (abscess, skin the included the On a other diagnosis of presentation demonstrated Differential No tissue tissue of healthy. palpated. subcutaneous extremity. overlying time the otherwise the The within at was of his present malleolus. but was use child near mass limiting earlier, extremity the palpable pain, lower months tender, and daily right noted noted causing the was size were of mass in swelling A increased onset had new 1). with (Figure presented extremity ankle lower male the 13-year-old of A malformation venous Localized of 1: care Case the in oncologist, and will CASES we hematologist patients, III. pediatric complex the these including malformations. manage local- vascular disciplines, to describe become simple, with multiple needed we of will patients often of review, strategies tissue is role management this of team and the In multi-disciplinary analysis options, examine a diagnostic available. Genetic As features, increasingly (7). clinical malformations. become the ized VMs therapy examine in targeted and risk, positive cases for without stain four options associated can not SMA are as LYVE-1 architecture and is and usually important vascular (podoplanin) CD31 Biopsy is more of D2-40 imaging examination while vessels. present. (6), and and lymphatic origin markers are evaluation with endothelial Immuno-histochemical clinical features confirms CD34 general, atypical bleed. diagnosis. In to if clarify prone needed (4,5). are is lungs lesions or ranging biopsy proximity as impact airway close occasionally clinical to the of but due variability as symptoms wide diagnostic, such life-threatening a even structures exhibit and They nature. vital (2). concerns, in development (3). to cosmetic extensive fetal childhood to more early during lesions, or in acquired asymptomatic or area, mutations from birth somatic body at from specific present in arise will a Most mal- non-proliferative to to arteriovenous thought are localized or are (which (VM), be malformations venous malformations can Vascular (LM), Malformations 2) lymphatic general and (CM), (1). broad (AVM) capillary nature) two to formations in are refer proliferative There malformations to Simple are continues anomalies. (which vascular and nature). approaching tumors proposed, for initially 1) system (ISSVA) classification Anomalies groups: Vascular held diagnosis, of widely Study a the the update, discuss for to Society International means malformations. The a vascular as localized cases simple, of four INTRODUCTION strategies presents II. single management review and a diagnosis arteriovenous This features, the to imaging and in involved disorders. localized and venous, increasingly clinical these are lymphatic, becoming of that is capillary, oncologist management malformations include and and of hematologist malformations non-proliferative. pediatric group simple are The These a vascu- malformations malformations. and to while involvement. tumors refer nature, of vascular malformations in area subtypes: proliferative vascular distinct are two localized into tumors Simple, divided Vascular disorders of malformations. group lar a are anomalies Vascular I.ABSTRACT 9 L,ddmro 5 gm (normal ng/ml 455 of d-dimer /L), MHLwmlclrwih heparin weight molecular rapamycin Low sulfate of tetradecyl target Sodium Mammalian LMWH Syndrome Klippel-Trenaunay mTOR malformation STS Venous KTS VM 2 < 0 gm) n bioe f20mg/ml 250 of fibrinogen and ng/ml), 500 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. gnsaepruaeul netdit h M ceohrp a eue ln o ypoai eif or relief, symptomatic for sclerosing alone procedure, of used this rounds be In Multiple can symptoms. Sclerotherapy sclerotherapy. clinical VM. to the and amenable into size is injected lesion which percutaneously on VM are depending be agents symptomatic may needed Analgesics focal, be ectasia. may small, venous sclerotherapy a of had development always patient the should slow This Compression pain. or moderate prevent (23,24). pain help to mmHg can mild causing 20-40 it of for not as pressures used garments recommended typical VMs, are are Compression with in garments which comfort, encouraged compression presence Custom and alone. be VMs tissue, fit pain. observation focal adjacent with proper with help ensure into Small, and conservatively to extension stasis, treated reduce lesion, and appearance. often the flow vascular of are aesthetic improve location impairment or on functional impairment, dependent or functional is VM pain, a of treat to after decision areas (21,22). obtained The hyperintense structures but images contain surrounding malformations, weighted to vascular may relationship T1 of but and classification on Management extent hypointense the enhance lesion in or determine VMs aids can iso- only also not appear calcifications. it MRI images they or weighted administration. T2 images, fat, contrast on intravenous weighted hyperintense products, appear T1 blood VMs On (MRI), shadowing representing imaging posterior resonance with 2). magnetic foci on (Fig hyperechoic patient, a this as in they (20). appear As exam, VM they On for US, the VMs. pathognomonic On to of considered contributes (19). occurrence flow are common nodules be blood and a hardened may Slow and as malformation (18). thrombosis palpated the painful thrombosed If are have are within may which (16,17). flow vessels phleboliths, waveform waveforms, or of venous Doppler spectral detection, development with monophasic and/or and sonographic or flow for a flow, compression slow color or slow releasing too waveforms demonstrate upon demonstrate augmented not no VMs be reveals does can surface. analysis Doppler that skin Spectral flow color the maneuvers. no near Valsalva to vascular if minimal anechoic shows compressible containing typically typically are analysis lesions lesions with heterogeneous The taken as be appear channels. must VMs Caution bleed. or examination, exam to considered. ultrasound physical clinicians propensity be Under on their must Experienced present given biopsy are malignancy. present, lesions features vascular is out unusual history of rule If versus clinical biopsy and optimal. concerning malignant diagnosis are if between examination entities or a Clinical these imaging, distinguish to with mass. lead to onset familiar new generally radiologists a upon and of can differential called imaging the on often with be combined is should anomalies vascular oncologist and masses, and benign hematologist pediatric The The integral other is (14,15). with which (3). adhesion (12,13,14), associated and receptor (KTS) Diagnosis be TIE-2 migration may Syndrome (4,10,11). the proliferation, and in Klippel-Trenaunay vascular growth mutations diffuse of as gain-of-function to or regulation by such to lead caused focal are be syndromes, can VMs Trauma, can of characterized pregnancy VMs majority (3). in or occur (4). puberty types most can occur during VMs malformation not adulthood While changes does or (9). regression hormonal adolescence colored positions Spontaneous in or bluish (2). dependent presentation with on hemorrhage, births delayed masses or 10,000 infection, childhood, maneuvers subcutaneous Valsalva per in soft nerves, with 1-2 joints, appear as enlarge muscles, of present commonly tissue, can VMs incidence subcutaneous They commonly, involve an can Most skin. but with overlying (4,5,8). mucosa, malformation, or organs vascular skin internal the of and in type located typically common are most VMs the are VM and malformation, Background venous pure management. a for with Approachx (VIR) diagnosed radiology was interventional vascular patient to The referred mg/ml). 213-435 (normal \ 3 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 1-3 gm) ata rtrmi ieo 8scns(oml2 eod 2seconds), seconds). 32 13.1 - Background to seconds seconds 24 11.5 150,000- (normal (normal (normal seconds seconds Approach: 275,000 12 28 of of of time count time prothrombin prothrombin platelet and d-dimer. partial elevated a mg/mL), given revealed hematology 213-435 the bleeding analysis pediatric other She in to laboratory no complications. increase 450,000x10 referred but recent bleeding weather, but slight or most dry thrombosis VIR, a of Her by with history note nosebleeds examined family but short initially also significant was occasional no garment, and is has compression There She malformation, custom 18 symptoms. the VM. occasionally the a can At the to Parents within wearing of with therapy. hue tenderness size with nodules aspirin 4). of bluish despite compliant of hardened concerns (Fig malformation diagnosis is a parenteral her palpate her mass given She from had After aspirin pain colored VM. of she developed lesion. a blue daily lately birth, with the mg/kg compressible, consistent 3 of At was on a palpation which started MRI with was pain. an she along underwent hand VM, she thumb left age left of with months her presents of female fingernail old fevers Phleboliths 5-year with with attention A malformation medical venous seek Localized (PJP). to pneumonia 2: advised jiroveci Case are pneumocystis sirolimus against and receiving (38). prophylaxis reduction benefit Patients prescribed sirolimus suppression, dose treatment either are count (39). of with mucositis, between and therapy reversible include are use balance of therapy effects dose studies sirolimus side cessation the the for These of multiple or levels and with effects enzymes. trough VM, liver type, side of symptoms increased Potential lesion monitoring and with pain effects. hypercholesterolemia, with on patients side hours, and depend for 12 In every potential size levels dose the lesion trough per anomalies. Target mg/m2 of highly 0.8 vascular reduction be adjustment. at of to dosed patients in shown generally variety sclerotherapy, is been benefit wide to Sirolimus has a which amenable a sirolimus. inhibitor, described VM of with (mTOR) use have localized rapamycin the patients of consider a in can target had candidates mammalian effective patient non-surgical oral or an the sclerotherapy is to as Sirolimus responsive case not VMs this larger focus to not with by should applicable loss as are approach blood not curative, surgical which minimizing be While A and lesions not structures, (37). (35,36). neurovascular may for needed surgery critical or if after appropriate of may approaches preservation remains appropriate surgery be staged area, tissue lesion, anatomical vascular with may defined the if excision approach a of regrow on if extent to This prone the VMs are on symptomatic structures. VMs Depending with vital sclerotherapy. patients to injure amenable in not considered does six be pain margins minimal can and tissues intervention swelling surrounding decreased Surgical damage with sclerotherapy, 3). and to (Fig choices. risk structures response given treatment nearby acceptable positive mucosa after affect a the be commonly months involving may had nature would of VMs patient which superficial (STS) or This selection necrosis lesions, the sulfate (29,30). a and superficial Given tetradecyl nerves, edema lists near sodium inflammation, effects. 1 embolizing lesions endothelial or for Table side for by avoided bleomycin proper potential or be (28). above, without and tourniquet, should plugs described Alcohol action, VM a or lesion of of the prior coils the mechanism use of needed agents, by of their out is embolic accomplished agents, different flowing veins be liquid sclerosing outflow from of can used with of it control number drainage vein(s) prevent to occlusion venous a outflow ability to of present, the on as agent Occlusion is dependent well sclerosing drainage time. as is sclerosing the venous contact structures), agent the of robust adjacent sclerosing to injection If to related of to proximity subsequent generally (26,27). Choice and of is drainage (depth, VM. success sclerotherapy venous location the improve of VM within to efficacy including time performed The factors, dwell is (25). sclerotherapy and surgeries pre-operative agent which debulking in or approach excisional staged a in 9 L,ddmro 20n/l(normal ng/ml 1200 of d-dimer /L), 4 < 0 gm) bioe f22m/l(normal mg/ml 272 of fibrinogen ng/ml), 500 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. a o niie.Oeligsi a omlapaac.Utaon eelda30x11x blood 1.1 motion Complete x of malformation. 3.0 Range vascular a for a revealed neck. notable for Ultrasound left is concerning lower appearance. lesion exam normal the subcutaneous His a on complex has 2x3cm cm sweats. skin measuring 2.6 Overlying further night mass On inhibited. or tissue malignancy. He not loss, soft for was apparent. recently weight concern tender, became He unintentional of mobile, mass out fever, mass. the a oncology illness neck denies and this right he hematology during onset history, pediatric and new to infection, for referred respiratory pediatrician was upper his viral to a presented had pre- male weeks two 8-year-old for An Malformation LMWH Lymphatic administered Localized be normal Special 3: of patients Anomalies Case limit that Vascular recommended upper the Oncology the (55). from and times post-procedure Hematology five guidelines and Pediatric than published of greater both Prior Society including guide d-dimer American complications, to with known. the data procedural of evidence-based not for Group of risk is Interest peri-procedural lack at thrombosis, a patients the is places and regarding which there bleeding discussion Unfortunately, threshold resection, d-dimer warranted. pain. The be surgical in would improvement approach. or LIC with sclerotherapy complica- lovenox her potential of undergone of and the dosing management had to difficult prophylactic regards on patient be in started would present this was were resection If patient concerns Surgical This similar and sclerotherapy. chosen. damage, of was patients muscle tions management adult or medical nerve in to hand, use lead the their could on of a (53,54). location play on reports symptoms may the Case depending continuous agents LIC Given LIC. these or in needed children, improvement associated episodic be in shown VM have use either may for for VMs requiring day) anti-coagulation approved with patients in become a function, anti-coagulants role with twice renal oral significant variable, direct count, mg/kg more is the dosing blood (1.0 As treatment prophylactic complete LMWH (52). of on of dosing of Duration started monitoring dosing typically appropriate Treatment response. are with patient Patients LMWH, levels. molecular of choice. low LMWH day) generally first and and a of (46), twice agent antagonists anti-coagulation. mg/kg K of the A vitamin initiation (0.5 is to to considered. (LMWH) response prior be of completed heparin lack can be weight less a anti-coagulation should documented either bleeding symptoms, have of improve as studies were history Prior selected not manifested bruising family does and in response, and Bleeding aspirin personal positive helpful VM. If thorough of a be shrinkage (51). obtaining and may fullness/swelling, complications participants decreased Aspirin reported of pain, patients shooting of 45% survey less aspirin. reported retrospective pain, A with aching aspirin efficacy. on treated and safety VMs initially analyzed have with was studies prospective LIC no although symptomatic patients, patient, this In hardened painful as exquisitely exam be physical can and on Management time, palpated As over are calcify (49,50). and which complications thrombi VMs, intravascular thromboembolic in of (19). present for because be factors occur malformation, They can risk of thromboem- phleboliths be extent nodules. of above, larger to reports patient age, shown case the the Increasing been rare, as with have (47,48,49). be important, phleboliths to reported thought is palpable been While have and distinction VMs (46). This from different char- complications is is Kasabach- thrombocytopenia. bolic conditions KMP two the profound hemangioendothelioma while these from kaposiform consumption, and of factor LIC as consumption management as clotting distinguish such by such platelet predominantly to stressors tumors by characterized of important vascular is acterized LIC setting is in the angioma. It occurs in tufted and which and (45). occur system (KMP), can surgery coagulation DIC phenomenon or the overt of Merritt (44), to activation sclerotherapy slow to Progression (43), but lead (42). unknown, to infection factors is thought the LIC clotting more is driving in channels of with mechanism and venous consumption associated exact d-dimer, malformed elevated The are within in- by flow phleboliths thrombocytopenia. characterized size, coagulopathy, blood and palpable malformation consumptive fibrinogen of a Large low is presence cases, LIC severe VMs. and (40,41). with nature, LIC patients diffuse of presence in structures, common deep is of volvement (LIC) coagulation intravascular Localized 5 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. sdpneto h ceoigaetue,deltm,adtp fL.Hge ae fcr r enin seen are cure of rates Higher LM. of type and time, sclerotherapy of dwell is success fluid used, VMs, a lymphatic agent to so space, hours, Similar sclerosing 48 cystic (37,64). to the the 24 injections on over into repeated injections inserted dependent facilitate multiple is treatment require to is may inserted needle preferred cysts is the a Large catheter be LMs, injected. pigtail Given would is of agent sclerotherapy age. treatment sclerosing of above, For and months patient drained, 6 patient. the least this of at for is nature patient course symptomatic the until and quality improved performed location an not the to often shown leading is general, sclerotherapy been in symptomatic, has size Unless sirolimus the decreasing with less but also therapy is and (66). above, medical but lesions life lesions patient the (64), of softening lesions microcystic the in micro/macrocystic In beneficial to lesions. mixed be (65). macrocytic or offered to LMs of macrocystic be treatment with microcystic for with treatment patients could for rates procedures line efficacious in Surgery success first debulking high successful the given but indicated. is approach most (37), Sclerotherapy reasonable be is most structures may LM the with adjacent is malformations for treatment important sclerotherapy treatment complex invade medical Surgical or not large, sclerotherapy, do for surgery, combination. that include in malformations options or localized indicated, alone is either observation treatment sirolimus; careful If is of concerns, cosmetic features LM significant warranted. or imaging a is impairment key functional unless without summarizes patients seen, 2 asymptomatic MRI. In Table be and CT (61). should US, mass component ultrasound, including solid either image to enhancing modality a US Treatment as Similar imaging solid as The LM. by classified No macrocystic appear VM (62). be a can and mixed with can LM masses. it or consistent both LMs case size) was cystic which and in as 5B, (60,61). in cm present and chyle 1 microcystic 5A LMs than or Fig (greater MRI, pus in macrocystic seen on blood, size), is levels contain patient in Fluid this cm spaces masses. for 1 cystic cystic multi-loculated than the as (less present if microcystic LMs present exam, ultrasound be on infection, may vignette, the viral in or described bacterial As with associated addition be in arise can may Diagnosis swelling (59). issues and bleeding speech intra-lesional pain or or feeding, Increased airway, trauma, from the inflammation, ranging (58). of of involvement LMs, concerns impairment for to cosmetic functional propensity secondary their area, sur- to Given symptoms neck proliferation, clinical and complications. mutation cell significant head of function cause the increased spectrum that of wide those in to gain a resulting lesions is This pathway, asymptomatic phosphatidylinositol- (56).There PI3K/AKT/mTOR the angiogenesis (57). active in and gene mutations constitutively vival somatic (PIK3CA) a to alpha KTS to due as subunit or are leads scoliosis/skeletal/spinal such hue, LMs catalytic syndromes and bluish of 3-kinase other a nevi majority with exhibit 4,5-biphosphonate epidermal The associated can and malformations, (56). but be head vascular (CLOVES) skin, can the overgrowth, anomalies overlying LMs in normal lipomatosis located (11). often congenital commonly blebs with most or or masses vesicles are soft lymphatic and are associated adolescence, they have KMP. or exam, with childhood, On (42). early associated area. elevation birth, neck be of at can degrees present which varying having can typically have tumor LMs LMs often vascular with VMs types, a while malformation to out between levels institution’s obtained distinguish rule d-dimer our help often are helps to normal are fibrinogen used tests labs and be of d-dimer, screening can testing, d-dimer malformation, cohort Additionally, coagulation of This CBC, type a case, of screen. this question standard In a clinician. is the there guide when help imaging, any to Prior Background: (normal mg/ml 256 was (normal). Approach: d-dimer seconds 14.5 normal, PT were and acid seconds), uric and LDH < unremarkable, was count 0 gm) bioe 6 (normal 262 fibrinogen mg/ml), 500 > 5 gd) T 0scns(oml2 seconds-32 24 (normal seconds 30 PTT mg/dL), 150 6 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. h ik n eet ftetetetotosfrbt ye fAM.Taiinlypoeue uhas such procedures Traditionally AVMs. of multi- types a of both Otherwise, consideration for through care. options outcomes guide treatment optimal to the promote neurosurgery of to of benefits help inclusion and will the intracranial risks decisions either to the as clinical leads classified to are lesion they approach cranial and disciplinary location, A on dependent extracranial. is AVMs or of management to approach (74). AVM The heart the output across can high shunting screening for of monitoring appropriate degree routine Management so the AVMs, crucial on with brain, is patients depending the diagnosis In necessary in Early is (73). occur complications failure telangiectasia. can avoid AVMs mucosal to to to warranted (HHT). penetrance. completed variable telangiectasia is addition be with hemorrhagic examination in fashion hereditary physical liver dominant carotid as and or autosomal such external history lungs, an syndrome in family the genetic inherited complete systemic from is a a HHT branch child, for a small possibility in the a syndrome. diagnosed assess steal and is or AVM arterial artery AVMs The an intra-cranial subclavian When space. of revealed right carotid evidence the ultrasound the no to had an from posterior connection She inferiorly patient, arise vascular artery. lesion extending hypervascular to the this space, with abnormal retropharyngeal while appeared communication In an the flow, showed clear supply in contrast venous level a (72). without C2 exhibited with and the well abnormally malformation with at neck/shoulder, as MRI The to right AVMs waveforms. due and the artery. arterial of is location demonstrated of carotid feature which on musculature common a right the depending bruit, the in symptoms is a malformation of Pulsation demonstrates vascular variety typically a wide flow. auscultation a blood examination, with physical high present On or incidentally, size. found (71). be syndrome steal can as AVMs can known AVMs phenomenon through a when flow children in High in pain, any Diagnosis (70). higher and for consideration ischemia, is complication higher hypoxic rupture feared of of hypoperfusion, most intervention rate to the timely The lead is making veins Rupture warranted. adults, ectatic always rupture. to progressively almost bypasses eventual compared is and is with system connections intervention flow, venous vascular therefore the blood abnormal (69). and to velocity AVM these children connects high of in directly the history diagnosed artery to natural an malformation due when The vascular occurs common beds. and least capillary lesion the flow the high are a and is age AVM An any at or present may history AVMs medical other no rest is Background and there pain, Acetaminophen note, denied Of epistaxis. changes. she or approach: headaches. visual and issues severity, vascular severe with ago, varying of more of months associated history headaches the 3-4 (Fig not intermittent family her for endorse about region and to does relief this clavicular weeks, She visit provide noticed right 2 well they her every area. annual over that the occurring to area regular report trauma pulsating parents her or raised Her bleeding, for round, presented a female 6). noted healthy who previously pediatrician, old 9-year time over An re-expand with can malformation treatment LMs Arteriovenous to well (37). 4: respond response CASE favorable LMs less Macrocystic a procedures. (68). have repeated toxicity lesions causes require dose with mixed which cumulative and associated or the bleomycin, complication is than microcystic nerves, potential that smaller but a to much greater OK-432, is typically close or toxicity are mg are pulmonary sclerotherapy lesions dependent 400 or in For Dose of doses for orbit (34). Bleomycin airway, (65). rates rate therapy. choice the success bleomycin efficacy of involve of 80% highest agent which an the the area, demonstrating is has neck swelling, LM Doxycycline neck minimal and and head treated. head the treated be of in can meta-analysis endothelium a entire with LM, the as LMs, macrocystic 7 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. rw,tree hrp rgnlydvlpdfroclgcidctos uha RSihbtr,wl lya play will malformations. inhibitors, of vascular KRAS care of References malformations as treatment the vascular such the for in or indications, in basis oncologic role resection, role genetic for substantial ever-increasing surgical the developed more an of management, originally understanding playing therapy medical our targeted is involve As grows, oncologist can malformations. and dependent but vascular is with hematologist location, malformations patients pediatric vascular imaging, lesion of The and and Management exam malformation present. sclerotherapy. clinical are of through features type accomplished atypical their often if on to is approach indicated multi-disciplinary is malformations a biopsy vascular require but simple and which of impairment lesions Diagnosis cosmetic develop children or care. Other functional, observation. chil- pain, many expectant significant with require cause widely, which vary include lesions symptoms which asymptomatic Clinical lesions having of dren malformations. population arteriovenous heterogeneous or a venous of lymphatic, composed capillary, are malformations vascular testing localized genetic Simple, no was has note, She She Of sampling. AVM. MRI. imaging. tissue in and Summary MRI biopsy increase exam IV. by of or both and lack recurrence with to without exam annually years due clinical then 5 performed and on for year was both procedure a weeks, smaller post for 2 became followed months every ascending been lesion 6 procedures, origin, every Her embolization followed common 3 and response. underwent and asymptomatic She good and trunk a thoracic arteries. thyrocervical better had occipital upper the allow right and right from and to the supply cervical within performed deep blood malformation was cervical, significant a order utilizing angiogram with revealed in embolization cerebral and regions, used selective vasculature, cervical A was A anatomic sirolimus AVM. the (80,81). peri-procedural the of the collateralization addition, of visualization in In size post-embolism pain in (79). decrease cramping increase performed to with was an re-presented (Onyx) patient was increased cyanoacrylate the there for n-butyl later, monitor and with months to area asked six embolism supraclavicular were Approximately elective parents right non-urgent The symptoms. a new year. Therefore, next or (78). the size resolved. underway in headaches recommended are may was patients AVMs studies radiology the for several interventional therapies visit, and medical initial future Therefore, her the Following of in (76,77). aberrant inhibition treatment inhibitors to to for AKT lead response modalities as mutations radiologic such new describe These agents, be have reports biologic (76). case investigators with AVMs Several several path pathway. and Recently, this signaling mutations MAPK KRAS (75). the somatic of management activation with AVM therapy association for radiation and interventions an placement, primary reported coil glue, the for considered chemical a are using embolization resection, endovascular surgical Chl M isE.Pdarcvsua afrain:ptohsooy igoi n oeo inter- of role and diagnosis pathophysiology, malformations: vascular Pediatric EL. Nijs AM, Cahill 10. BhaehS ae ,GpaN ta.Vnu afrain:ciia igoi n treatment. and diagnosis clinical malformations: Venous al. surgical et N, calf: the Gupta of W, malformations for Yakes venous marker Intramuscular S, common Behravesh al. a et 9. N, as Paraskevas CD34 P, anomalies. vascular Cerceau for of C, evidence Histopathology Laurian H. review: 8. Kozakewich A, Concise Gupta SE. comprehensive 7. a Dunphy neck: MJ, and Branch head LE, the Sidney of malformations malforma- 6. venous Venous Understanding AK. IM. Greene Ieraradi D, Zurakowski G, AI, Colletti Alomari 5. anomalies. SJ, malformations. vascular Fishman of vascular JB, Pathogenesis Mulliken of M. AH, Vikkula genetics Hassanein F, Molecular 4. Ballieux LM, JB. Boom Mulliken 3. 2020. LM, 1, October Boon Accessed M, 2018. Vikkula Published http://www.issva.org/classification. 2. Classification. 2018 1. etoa radiology. ventional Ther Diagn Cardiovasc patients. 57 of outcomes treatment progenitors. diverse adolescence. insight. and childhood during progression of risk tions: 2001;20:327-335. e Oncol Med 073() 896-899. 2017;34(3): . tmCell Stem adoa nevn Radiol Intervent Cardiovas 2016;6(6):557-569. . 2014;32(6):1380-1389. . Phlebology 2020;35(8):597-604. . 8 2011;34(4):691-704. . n ls Surg Plast Ann lnPatcSurg. Plastic Clin lnPatSurg. Plast Clin 2012;68:198-201. . 2011;38:31-44. 2011;38:7-19. arxBiol. Matrix Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. Dfe M ardaN enne Le l eiti ypai afrain:eovn under- evolving malformations: lymphatic the Pediatric in al. malformation et venous SL solitary Hernandez of N, management Bagrodia malformations. Surgical venous AM, of Defnet management al. 37. Surgical DA. et Loose WJ, 36. Yang A, Ow head the 2013. LP, of group. Zhong malformations oncology lymphatic 35. Children’s for Sclerotherapy alert. al. bleomycin et link: K, Health Balakrishnan PD, al. Sanctis et L, treatment K, Maria the neck. Stormer de for bleomycin and E, and 34. Walz ethanol head M, absolute the between Schaffer Comparison of 33. al. malformations et of SY, lymphatic Zhou update HB, for sclerotherapy. Li an of J, Sclerotherapy Zhang Pharmacology children: KL. 32. al. Kondo in G, et lymphangiomas Albanese V, of 31. Patel Treatment HM, Do al. JH, et Tu Y, 30. Sato DK, are, radiology. Burke we interventional where JH, by data, Greinwald approach the 29. malformations: malformations: venous Vascular of Treatment S. al. Pimpalwar complications et 28. J, malformations: Srinivasa vascular JF, for Chick Sclerotherapy AN, al. Hage et 27. 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(OK-432) picibanil 2014;28(2):91-193. done. is it how avoid. to techniques of review a and follow-up term long and parameters surgical on impact Disord Lymphat Venous Surg Vasc J review. systemic a extremities- the of malformations vascular follow-up. therapy and classification, ultrasound. Doppler with diagnosis patients: neck. and head the of malformations malformations. vascular 2: part Surg Maxillofac Oral issues. therapeutic formation. vessel blood malformations. venous sporadic multiple and solitary TIE2. kinase tyrosine receptor the in 2014;23:221-226. Pediatr 2015;27(3):356-363. . ehVs nevRadiol Interv Vasc Tech rlSr rlMed Oral Surg Oral Radiographics 2014;72(3):510-528. . Nature. eit Radiol Pediatr 1995;376:70-74. 2001;21(6):1519-1531. . tlrno edNc Surg Neck Head Otolaryngol eit ugInt. Surg Pediatr ls eosrAshtSurg Aesthet Reconstr Plast J x hrMed. Ther Exp Phlebology Cell Radiographics 2017;5(4):587-595. . 2012;114:160-166. . 2018;21:45-54. . 1996;87(8):1181-1190. . 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Hematology/Oncology; Pediatric of Society American The IL: Chicago, 2019;26:185-192. . rhDermatol Arch 2021;36(1):38-42. . u eit Surg Pediatr J Eur rhOoayglHa ekSurg. Neck Head Otolaryngol Arch eit lo Cancer Blood Pediatr eit Surg Pediatr J 2008;144(7):873-877. . eit mr Care Emerg Pediatr 2017;27(02):181-184. . 2011;57(6):1018-1024. . 2016;52(3):400–410. . LSOne PLOS 10 rJDermatol J Br Pediatr J 1995;121(5):577-582. 2013;29(3):371-373. . 2018;13(7):1-18. . mJRoentgenol J Am eit hl Health Child Pediatr J e Derm Ped aclrAoaisSeilInterest Special Anomalies Vascular e nshCi Care Crit Anesth Ped 2007;157(3):558-563. . ypa e Biol Res Lymphat 2015;166(4):1048-1054. . rhOoayglHa Neck Head Otolaryngol Arch 2014;31(5):556-560. . hobThrombolysis Thromb J 2001;177(6):1359-1363. . lnLbHaematol Lab Clin 2018;16(3):278- . 2017;53(8):737- . lnPatSurg Plast Clin rn Pediatr Front 2015;3(1):22- . Curr . . . . Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. otdfile Hosted localized-vascular-anomalies 1.pdf Table file Hosted CeihM,D ,Zn ,e l aaeeto ope reivnu afrain sn Novel a Using Malformations Arteriovenous Complex of Management al. et Z, Extracranial Zinn for (Rapamycin) H, Sirolimus Do of MP, Tolerance Cheliah and Efficacy complica- 81. techniques, al. et embolotherapy: V, Soupre cyanoacrylate O, N-butyl Boccara R, R. Gabeff Srinivasa Arteriovenous Monitoring A, 80. Hage. KA. Shimano JF , Chick HJ H, Fullerton Hill an MA, of 79. Zapala Treatment Medical IJ, Frieden Genotype-Guided D, J. Cooke Teng EA, arte- KJ, Phelps Choate in 78. S mutations Admani KRAS YH, Activating Lim K. R, Lekwuttikam Curless 77. HY Pe- Chang for S, Embolization Zhang of AO, Outcomes Vortmeyer Treatment DS, re- al. Priemer as et presenting 76. BH, malformations Verhoeven arteriovenous SMBI, Pulmonary Botden W. arteriovenous FCM, Song Bouwman telangiectasia: G-Y, 75. hemorrhagic Huang Hereditary K-H, Chen and al. Y, variables et Liao P, Prognostic 74. Suppressa G. GM, Marquardt Lenato V, P, Seifert Giordano J, 73. management. Berkefeld and J, evaluation Quick-Weller AVM: SY, Cerebral Won al. N, et Dinc Pop- RM, Pediatric 72. Starke the in N, Malformations Chalouhi Arteriovenous N, al. Ajiboye et O 71. Kass-Hout malforma- arteriovenous T, of Kass-Hout management , micro- and M for Diagnosis El-Ghanem C. sclerotherapy Raffel bleomycin 70. RC, of Anderson efficacy Jr, flow and P low Klimo Safety TN, of al. Niazi management et in 69. KL, bleomycin Rialon of CJ, injection Guevara Intralesion G, al. patients Chaudry 19 et 68. for K, treatment Adams as S, Sirolimus Adams CC. AT, Trenor Mohan H, Padua 67. MJ, O’Hare treatment. R, current Rahbar of review JE, a Strychowsky malformations: Lymphatic 66. malformations. lymphatic al. et lymphatic macrocystic RM, Tempero of cervical SC, Manning Management of JA, Perkins AI. treatment 65. Alomari surgical malformations. CA, venous and neck Perlyn and Diagnosis head AK, of Greene Imaging al. SE. 64. Connor exami- et CM, clinical F, Flis from Lou 63. pitfalls: R, malformation vascular Biao flow Low J, treatment. al. Ma and et diagnosis 62. R, Restrep malformations: B, Lymphatic Olivieri CL, al. White et HM, 61. Padua K, Balakrishnan RG, Elluru 60. obnto hrpui Algorithm. Therapeutic Combination Adults. and Children in Malformations Arteriovenous management. and tions, Therapy. Genotype-Targeted to Response Malformation Child. a in correlation. Malformation clinicopathologic Arteriovenous and frequency brain: the 2019;89:33-39. of malformations riovenous Malformations. Arteriovenous ripheral failure. heart fractory children. in malformations. malformations arteriovenous in patterns bleeding different to 2019;42(3):731-736. relation in outcome Journal World Literature. Existing the of Review ulation: children. in tions malformation. lymphatic cystic children in malformations vascular malformation. lymphatic cervicofacial refractory with Surg Neck Head Otolaryngol 2011;38:75-82. infants. in malformation evaluation. imaging practical to nation Surg Ped in Seminars Surg 2010;136(3):270-276. . vial at available 04 1-6. 2014. . ersr lnNAm N Clin Neurosurg https://authorea.com/users/405595/articles/516537-how-we-approach- hrcDis Thorac J 2014;23(4):178-185. . ig nevRadiol. Interv Diagn x hrMed. Ther Exp Pediatr J 2010;142(6):795-803. . adoacItretRadiol. Intervent Cardiovasc ls ugadHn Surg Hand and Surg Plast J . 2013;163(1):179-86.e1-3. . 0469:E169–E172. 2014;6(9): . AADermatol. JAMA mJo Rotentgenology of J Am acItr Radiol Interv Vasc J aaDermatol Jama 2010;21(3):443-456. . 2017;14(2):1293-1298. nevNeurol. Interv 08 42:98–103. 24(2): 2018; 11 Laryngoscope caDr Venereol Derm Acta 2019;155(2):256-257. 2018;154(11):1316-1319. Pediatrics 2016;5(3-4):218-225. 2014;37:1476-1481. 2020;1(11):1801-1809. . 2016;206(5):940-951. . 2015;49(2):116-120. . 2020;146(3):e3206. . 2018;128(1):269-276. . u Radiol Eur 2019;99(12):1105-1109. . 2005;15:2185-2193. . lnPatSurg Plast Clin ersr Rev Neurosurg u Pathol Hum Scientific . . . Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. localized-vascular-anomalies 2.pdf Table vial at available https://authorea.com/users/405595/articles/516537-how-we-approach- 12 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 13 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 14 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 15 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 16 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 17 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 18 Posted on Authorea 3 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161746184.45717973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 19