Vascular lesionsKomala Pillay

MBChB, FCPath (SA), FRCPath(UK), MMed Anat Path (UCT)

Histopathologist National Health Laboratory Services and University of Cape Town

Red Cross Children's Hospital

Vascular anomalies of skin and soft tissue

ISSVA WHOISSVA

• TUMOURS

WHO

Benign

• Haemangioma• Haemangioendothelioma

• Haemangioma (benign)Capillary, cavernous, AV, venous

• Lymphangiomag• Angiosarsoma

Lymphangioma• Angiomatosis

I t di t• MALFORMATIONS• Simple (slow flow) C,V,L

Intermediate• Haemangioendothelioma• Kaposi sarcomaSimple (slow flow) C,V,L

• Simple (fast flow) A• Combined, AVM,C-V,C-L,

Malignant• EpithelioidCombined, AVM,C V,C L,

L-V• Epithelioid

haemangioendothelioma• Angiosarcoma

Syndromes characterised by vascular malformations / haemangiomas

Bl bb bl b D S i C hi• Blue rubber bleb nevus syndrome

• Gorham syndrome

• De Santis Cacchione• Bloom syndrome • Ataxia telangiectasiay

• Mafucci syndrome• Proteus syndrome

Ataxia telangiectasia• Goltz syndrome• Xeroderma pigmentosa

• Sturge Weber• Kassabach-Merrit

• Turner• Rothman Thompson

O l W b R d HHT• Osler-Weber-Rendu HHT• Von Hippel Lindau• Bannayan syndromeBannayan syndrome• Riley-Smith

BENIGN

Arteriovenous malformation (arteriovenous haemangioma)

Cli i l f HiClinical features• Fast flow cutaneous

malformations

Histo• distorted arteries and veins• Irregularly thickened

• Present at birth, but only 30% visible at birthD t

Irregularly thickened fibromuscular walls and discontinuous elastic networkSt l fib i• Do not regress

• Purple colour or mass• Mainly head and neck

• Stromal fibrosis• Variable admixture of

capillariesMainly head and neck• Arterial embolisation – may

alter histology

p

http://ades.tmu.edu.tw/english/pcare/course/Hemangioma/small/Hemangioma.html

Venous malformation (venous haemangioma

M t l Histo• Most common vascular malformation

• Low flow

Histo• Poorly circumscribed• Complex network of ectatic

thin walled channels with• Localised or extensive• Head and neck

thin-walled channels with intermixed capillaries

• Thrombi may have recanalised• Calcification frequent• At birth but evident later

• Mafucci syndrome

• Calcification frequent

Clinical• Blue, may swell, expand

slowly phlebolithsslowly, phleboliths• Intralesional sclerotherapy and

Sx

Pathology NHLS,RXH

Blue rubber bleb Differential of ‘blueberry muffin

nevus syndromeS di

Differential of ‘blueberry muffin baby’

Dermal extramedullary• Sporadic• Skin and GIT mainly• Dome shaped, painful at

haemopoiesis• Congenital infection – rubella,

CMV Toxop ppuberty, recurrent GIT bleeding

• Histo – irregular widely dilated

CMV, Toxo• Haemolytic dx of the newborn• Twin transfusion syndromeg y

thin-walled venous channels extending from subcutaneous fat into deep dermis to

• Hereditary spherocytosis

Bl bb bl b dp

immediately beneath thinned epidermis

• May be recanalised thrombi

Blue rubber bleb nevus syndrome

Neoplastic infiltrationsy Neoplastic infiltrations neuroblastoma,leukaemia, RMS, chorioca.

Capillary malformations / Macular stainshaemangioma

• Localised or extensive

Macular stains• Port wine stain: Pink –

bluish red to purple –• Localised or extensive• Face, trunk or limbs• Facial – trigeminal nerve area

Gro s in proportion to child

p pdarker irregular thickened and nodular

• Naevus flammeus• Grows in proportion to child• Bright red at birth• Evenly thickened skin, purple

nodules and pyogenic

• Naevus flammeus –resolves with time – may remain and become li htnodules and pyogenic

granuloma develop by adolescence

• Sturge weber – ipsilateral

lighter

• Sturge weber – ipsilateral ocular, pial and facial vascular anomalies

• Histo – marked dilatation of sto a ed d atat o ocapillaries and venules in superficial dermis

http://emedicine.medscape.com/article/459842-overview

Angiokeratoma• Localised or widespread• Dark red to black papules• Many covered by scales• Widespread AK – Fabry’s,

fucosidosis and sialidosisfucosidosis and sialidosis• No systemic findings are

associated with localised i k t

http://ades.tmu.edu.tw/english/pcare/course/Hemangioma/small/H i ht langiokeratoma

Clinical• Verrucous dark red to black

Hemangioma.html

Pathology NHLS,RXHVerrucous dark red to black• Minute – Mibelli type• Large – angiokeratoma

circumscriptumHisto –• Widely thin walled vascular• Widely thin-walled vascular

channels in upper dermis• Closely apposed to epidermis

Epithelioid haemangioma• Angiolymphoid hyperplasia

with eosinophilia

Pathology NHLS,RXH

• Polygonal / epithelioid endothelial cells lining capillary sized vasculature withsized vasculature with lymphocytes and/or endothelial cells

Pathology NHLS,RXH

http://ades.tmu.edu.tw/english/pcare/course/Hemangioma/small/Hemangioma.html

Lobular capillary haemangioma (pyogenic granuloma

Si l l id d l h• Single polypoid nodule that bleeds easily

• Face and lip – common sitesp• Also appears at sites of trauma

and infectionL b l f lif ti• Lobules of proliferating capillaries and fibroblasts

• Epithelial collarette

http://drkevinbrenner.com/wp-content/uploads/2011/04/DSCN0016.jpg

Pathology NHLS,RXHp

• at the base of the nodule

Congenital HaemangiomaSKIN and SOFT TISSUE

Infantile / juvenile haemangioma

Rapidly involuting haemangioma ( C )

Non-involuting haemangioma ( C )

Congenital Haemangioma(RICH) (NICH)

Growth and involution

Rapid postnatal growth,

Fully grown at birth; regresses by 12-18m

Fully grown at birth; fails to involuteinvolution growth,

stabilisation, followed by slow involution

regresses by 12 18m fails to involute

Appearance Strawberry like bright red colour at birth

Protruberant, hemispherical, violaceous and firm with central scar /

Only slightly raised, pink-purple

with central scar / ulcer

Sex F:M 3-5:1 1:1 1:1

The pathogenesis of RICH and NICH has not been elucidated, whereas IH are postulated to arise from embolized placental cells or angioblasts that differentiate p gtoward a placental microvascular phenotype

3. Bruckner A, Frieden I. Infantile hemangiomas. J Am Acad Dermatol 2006; 55:671

SKIN and SOFT TISSUE

Infantile / juvenile haemangioma

Rapidly involuting haemangioma (RICH)

Non-involuting haemangioma (NICH)( ) ( )

Radiology Homogenous signal; uniform parenchymal

MRI – larger flow voids, inhomogeneity

Homogenous signal; uniform parenchymalparenchymal

enhancementinhomogeneityAngiography –arterial aneurysms and direct A-V shunts

parenchymal enhancementArteriography –dilated arterial feeders and drainingshunts feeders and draining veins, like AVM but without early venous filling

Pathology Fat in involution Thrombi, infarction, haemosiderin, calcification, cysts, aneursyms, EMH in

Thrombi

involutionArchitecture, lobules, endothelium,

overlap overlap overlap

endothelium, capillary bm and extralobar vasculatureGLUT 1 P iti N ti N tiGLUT 1 Positive Negative Negative

May be variations of a single entity Pediatr Dev Pathol. 2003 Nov-Dec;6(6):495-510.

http://www.saintluc.be/en/services/vascular-anomalies/vascular-tumors.php

http://www.pedorthpath.com/infantile_hemangioma_gross_new.jpg

Pathology NHLS RXH

Pathology NHLS,RXH

Pathology NHLS,RXH

Pathology NHLS,RXH Pathology NHLS,RXH

Glut 1

Rapidly involuting congenital hemangioma: clinical and histopathologic features.Pediatr Dev Pathol. 2003 Nov-Dec;6(6):495-510.Berenguer B Mulliken JB Enjolras O Boon LM Wassef M Josset PBerenguer B, Mulliken JB, Enjolras O, Boon LM, Wassef M, Josset P, Burrows PE, Perez-Atayde AR, Kozakewich HP.

The lesion was light blue violet in color with central coarse telangiectases and peripheral pallor

Noninvoluting congenital hemangioma Jennifer A Stein MD PhD, Noushin Heidary MD, Melissa Pulitzer MD, Julie V Schaffer MD, Paula North MD PhDDermatology Online Journal 14 (5): 7

The lesion was light blue-violet in color, with central coarse telangiectases and peripheral pallor.

http://dermaamin.com/site/atlas-of-dermatology/13-n/1017-non-involuting-congenital-hemangioma-.html

Angiomatosisg• Diffuse neonatal angiomatosis – occurs in the first year of life• Widespread capillary haemangiomas involving skin and viscera esp.

GIT, brain, liver, lung, and with occasional associatedplacental chorangioma

Pathology NHLS,RXH

• Soft tissue angiomatosis – occurs in newborns and infants, lower extremities and buttocks, haphazard proliferation of vessels of varying i i ll l i l i ith l t i f ill i dsize, especially large irregular veins with clustering of capillary sized

vessels in venous walls or adjacent soft tissue, large amounts of adipose tissue, tendency for local recurrence

• Association with proteus syndrome

http://www.pedorthpath.com/page04.html

• Skeletal-extraskeletal angiomatosis – medullary cavity of bone +1 other siteC di l l h i• Can display cavernous lymphangioma, cavernous haemangioma and arteriovenous haemangioma pattern

• Vascuar tumours of bone (haemangiomas and lymphangiomas) may be associated with extensivelymphangiomas) may be associated with extensive absorption of bone or osteolysis – Gorham syndrome

• Can cross joints and result in loss of entire region of theCan cross joints and result in loss of entire region of the skeleton.

Vascular lesions of the liverVascular lesions of the liver

• Confusing terminology – infantile haemangioendothelioma, haemangioma g , g(cellular, capillary and cavernous) and haemangiomatosis frequently used tohaemangiomatosis frequently used to describe similar lesions.

Infantile haemangioendothelioma of theliver

• Type 1: proliferation of well-formed capillary spaces lined by a single layer of plump endothelial cellsShares histologic features with haemangiomasg gat other sites – early life, multicentricity, rapid early growth followed by involution

• Type 2: metastases and death; believed to represent low grade angiosarcomasrepresent low grade angiosarcomas

Hepatic haemangiomasHepatic haemangiomas• Single masses or more often multiple nodules

• Dark reddish brown masses composed of blood vessels filled with blood with or without areas of fibrosis, calcification and haemorrhageg

• Many cases = juvenile capillary haemangioma, GLUT 1 positive, as mptomatic hepatomegal incidental finding in the first fe eeksasymptomatic hepatomegaly, incidental finding in the first few weeks or months, multiple small nodules

Hepatic haemangiomasHepatic haemangiomas• Other cases featuring large abnormal vessels and arteriovenous

malformation like areas in association with a GLUT 1 negativemalformation-like areas in association with a GLUT 1 negative capillary proliferation – more likely represent vascular malformation, commonly associated with infarction, haemorrhage

d l ifi ti ( i il t RICH) ll t ti t bi thand calcification (similar to RICH), usually symptomatic at birth with severe oedema and congestive heart failure

Pathology NHLS,RXH

• Cavernous haemangioma –mainly in adults

• Associated findings – Kasabach Merrit syndrome and anaemia

• Large unresectable or multiple lesions can be treated by hepatic artery ligation, transarterial y p y gembolisation or transplantation

Skeletal muscle haemangiomaSkeletal muscle haemangioma

• Small vessel, large vessel or mixed types• Can occur during first yearCan occur during first year• More frequent- 2nd to 4th decade• Small cell variant – cellular pattern similar

to infantile haemangiomato a t e ae a g o a• May be impossible to distinguish

histologicall from angiomatosis clinicalhistologically from angiomatosis – clinical correlation essential.

Lymphatic malformation / lymphangioma

L h i i i t

http://www.huidziekten.nl/afbeeldingen/lymphangiomacystichygroma.jpg

Lymphangioma circumscriptum• Plaque like lesion – skin and

submucosa• Vesicles• Recurrent cellulitis and

ecchymosesy

L h ti filli th d i- Lymphatics filling the dermis –• dilated, thin walled, may get

haemorrhageg

Pathology NHLS,RXH

http://www.huidziekten.nl/afbeeldingen/lymphan

Cystic hygroma / lymphangioma• Soft multilobular masses with slight bluish

discolouration usually involve large areas

http://www.huidziekten.nl/afbeeldingen/lymphangiomacystichygroma.jpg

discolouration, usually involve large areas• Limb - lymphoedema

– poorly circumscribed, numerous irregular lymphatic channels, with variable smooth muscle

Pathology NHLS,RXHPathology NHLS,RXH

and D2-40 esp. in small channels

Surgery,RXH

LymphangiomatosisLymphangiomatosis• Multiple• Diffuse involvement of bone, soft tissue and / or viscera

D2-40

CD34

Pathology NHLS,RXH

Intermediate

Infantile kaposiform haemangioendothelioma (KHE)

Ab h lf d bi h Diff f hildh d• About half – noted at birth or develop in early infancy

• Red or purple cutaneous patch

Differs from common childhood haemangioma

• Sexes affected equallyp p pthat rapidly enlarges, eventually becoming an indurated deep soft tissue

q y• Occurs more often on the

trunk, in the retroperitoneumand the proximal portion of theindurated deep soft tissue

mass• May be associated with

K b h M it d

and the proximal portion of the extremities

• Large and infiltrative Kasabach-Merrit syndrome

http://www.saintluc.be/en/services/vascular-anomalies/vascular-tumors.php

Histology KHE• Angiomatous – rounded or dilated vascular spaces lined by flattened

endothelial cellsendothelial cells• Kaposiform – infiltrating fascicles, sheets or nodules of spindled

cells lining compressed (slit-like) or crescentic vascular channels –peripheryperiphery

• Microthrombi, haemosiderin and hyaline globules• GLUT 1 negative• HHV-8 negativeRetroperitoneum – high mortality

Pathology NHLS,RXH

Pathology NHLS,RXHgy ,

Tufted angiomaTufted angiomaB i l l i Hi ll l b l• Benign vascular lesion

• <20% present at birth• Histo – small lobules or

vascular tufts scatterred in a multiple ‘cannon-ball’like’

• Slow growth, can cover large areas of the trunk and neck

distribution in the dermis and subcutis

• Overlap with KHE• Also head and extremities• May present with Kasabach-

Merritt syndrome

Overlap with KHE• Rapid expansion may require

surgical excisionMerritt syndrome

Tufted angioma. Schaffer, JV et al. Dermatology Online Journal. 2008 14 (10) 20Pathology NHLS,RXH

Endovascular papillary angioendothelioma

D b k• Dabska tumour• Intravascular proliferation• May be congenitalMay be congenital• Diffuse swelling or intradermal mass• Rare cases metastasizes to lymph nodes• Surgery is effective treatment

Retiform haemangioendotheliomaDabska-retiform haemangioendothelioma

Pathology NHLS,RXH

Composite haemangioendothelioma (CHE)• Heterogenous• Retiform HE epithelioid HE cavernousRetiform HE, epithelioid HE, cavernous

haemangioma, spindle cell haemangiomaR l it l• Rarely congenital

• Tendency for persistent growth with local e de cy o pe s ste t g o t t ocarecurrence and rare incidence of metastasismetastasis

Giant cell angioblastomaGiant cell angioblastomaR i l d i f il l• Rare congenital and infantile vascular tumour

• Head, neck and extremities• Concentric arrays of oval to spindle cells and multinucleate cells areConcentric arrays of oval to spindle cells and multinucleate cells are

arranged around small vessels

http://ades.tmu.edu.tw/english/pcare/course/Hemangioma/small/Hemangioma.html

Vascular anomalies of skin and soft tissue

ISSVA WHOISSVA

• TUMOURS

WHO

Benign

• Haemangioma• Haemangioendothelioma

• Haemangioma (benign)Capillary, cavernous, AV, venous

• Lymphangiomag• Angiosarsoma

Lymphangioma• Angiomatosis

I t di t• MALFORMATIONS• Simple (slow flow) C,V,L

Intermediate• Haemangioendothelioma• Kaposi sarcomaSimple (slow flow) C,V,L

• Simple (fast flow) A• Combined, AVM,C-V,C-L,

Malignant• EpithelioidCombined, AVM,C V,C L,

L-V• Epithelioid

haemangioendothelioma• Angiosarcoma

Take home messagesTake home messages

• Benign vascular tumours are very common and most frequently occur in the q yskin

• At all sites it is often difficult to determine• At all sites, it is often difficult to determine whether benign vascular lesions are

fmalformations, true neoplasms or, in some cases, reactive processesp

Take home messagesTake home messages

• Immunohistiochemistry in the context of vascular lesions:

• CD31 pan-vascular marker• CD34 > blood vessel endotheliumCD34 blood vessel endothelium• D2-40 (podoplanin) > lymphatic

endotheliumendothelium• Glut 1 glucose transporter protein - positive in

endothelia at sites of blood tissue barrier

Take home messagesTake home messages• Congenital infantile haemangioma (Glut 1 positive),

RICH and NICH (Glut 1 negative) have overlapping features and may be variations of a single entityfeatures and may be variations of a single entity

T pe I hepatic infantile haemangioendothelioma• Type I hepatic infantile haemangioendothelioma = haemangiomaType II hepatic infantile haemangioendothelioma =Type II hepatic infantile haemangioendothelioma = angiosarcoma

• Haemangioendothelioma – intermediate malignancy except epithelioid haemangioendotheliomaexcept epithelioid haemangioendothelioma

ReferencesReferencesDiagnostic paediatric s rgical patholog B Neil Sebire MB BS FRCPath Marian Malone MB BCh BAO• Diagnostic paediatric surgical pathology, By Neil Sebire, MB, BS, FRCPath, Marian Malone, MB, BCh, BAO, FRCPath, Michael Ashworth, MBBCh, FRCPath and Thomas S. Jacques, MA, PhD, MRCP, FRCPath. Churchill Livingstone, 2010

• Potter's Pathology of the Fetus Infant and ChildPotter s Pathology of the Fetus, Infant and Child• Enid Gilbert-Barness AO MD FRCPA FRCPath DSci(hc) MD(hc) (Editor), Raj P. Kapur MD PhD (Editor), Luc

Laurier Oligny MSc MD (Editor), Joseph R. Siebert PHD (Editor) , Elsevier Inc, 2007

• Stocker and Dehner's Pediatric PathologyStocker and Dehner s Pediatric Pathology • J. Thomas Stocker (Author), Louis Dehner (Author), Aliya Husain (Author) , Lippincott Williams & Wilkins, 2011

• Pathology and Genetics of Tumours of Soft Tissue and Bone World Health Organization Classification ofPathology and Genetics of Tumours of Soft Tissue and Bone. World Health Organization Classification of Tumours. Edited by Christopher D.M. Fletcher, K. Krishnan Unni, Fredrik Mertens

• IARC Press Lyon, 2002

Rapidly involuting congenital hemangioma: clinical and histopathologic features.Rapidly involuting congenital hemangioma: clinical and histopathologic features.• Pediatr Dev Pathol. 2003 Nov-Dec;6(6):495-510.• Berenguer B, Mulliken JB, Enjolras O, Boon LM, Wassef M, Josset P, Burrows PE, Perez-Atayde AR, Kozakewich

HP.

THANK YOUAcknowledgement: RXH NHLS Histopathology staffAcknowledgement: RXH NHLS Histopathology staff