Provisionally unclassified vascular anomalies

Michel Wassef M.D.

Dept of pathology and vascular anomalies clinics

Lariboisière Hospital

Paris, France

ISSVA classification for vascular anomalies

Paediatric and Perinatal Pathology

Update on vascular anomalies of childhood

ISSVA classification for vascular anomalies

Provisionally unclassified vascular anomalies

Intramuscular hemangioma *

Angiokeratoma

Sinusoidal hemangioma

Acral arteriovenous "tumour"

Multifocal lymphangioendotheliomatosis with thrombocytopenia / cutaneovisceral

angiomatosis with thrombocytopenia (MLT/CAT)

PTEN (type) hamartoma of soft tissue / "angiomatosis" of soft tissue (PHOST) PTEN

Fibro adipose vascular anomaly (FAVA) PIK3CA

Back to

overview

* Distinct from infantile hemangioma, from intramuscular common VM, PHOST/AST, FAVA and AVM

some lesions may be associated with thrombocytopenia and/or consumptive coagulopathy see details

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Causal genes in blue

Intramuscular hemangioma

Correspond to capillary type and part of mixed types

of WHO "intramuscular hemangioma"

T2

T1 T1 G fs

T1 T1 G

Intramuscular (capillary) hemangiomavs.

arteriovenous malformation

• Well delimited tumor-like lesion on imaging

– with capillary blush on arteriograms

– different from the nidus of AVM

– without early venous drainage

• Do not present the possible severe worsening of AVM

• May resemble AVM on histological small specimens

• Differences or identity with AVM need to be clarified

Pediatr Radiol 2014

ISSVA classification for vascular anomalies

Provisionally unclassified vascular anomalies

Intramuscular hemangioma *

Angiokeratoma

Sinusoidal hemangioma

Acral arteriovenous "tumour"

Multifocal lymphangioendotheliomatosis with thrombocytopenia / cutaneovisceral

angiomatosis with thrombocytopenia (MLT/CAT)

PTEN (type) hamartoma of soft tissue / "angiomatosis" of soft tissue (PHOST) PTEN

Fibro adipose vascular anomaly (FAVA) PIK3CA

Back to

overview

* Distinct from infantile hemangioma, from intramuscular common VM, PHOST/AST, FAVA and AVM

some lesions may be associated with thrombocytopenia and/or consumptive coagulopathy see details

Type Alt

for previous

view

Causal genes in blue

Multifocal lymphangioendotheliomatosis with thrombocytopeniaCutaneovisceral angiomatosis with thrombocytopenia

North, Arch Dermatol 2004, Prasad, Pediatr Dev Pathol 2005

• multiple congenital skin lesions

+digestive tract, lung, liver, spleen, muscle,

bone, synovium lesions

• platelets 30 000 to 50 000 / mm3

• normal fibrinogen, no D-dimers

MLT /CAT

Prasad, Pediatr Dev Pathol 2005

MLT / CAT

Yeung et al. J Am Acad Dermatol 2006

D2-40

CD31

CD31

D2-40

MLT / CAT

Esparza JAAD 2012 LYVE1

The endothelial cells

express common endothelial markers,

with partial lymphatic immunophenotype

• Lyve-1 positive

• VEGFR-3 positive

• Podoplanine negative (or weak / focal)

• Prox1 non published

The lesion associate features

of both tumors and malformations

ISSVA classification for vascular anomalies

Provisionally unclassified vascular anomalies

Intramuscular hemangioma *

Angiokeratoma

Sinusoidal hemangioma

Acral arteriovenous "tumour"

Multifocal lymphangioendotheliomatosis with thrombocytopenia / cutaneovisceral

angiomatosis with thrombocytopenia (MLT/CAT)

PTEN (type) hamartoma of soft tissue / "angiomatosis" of soft tissue (PHOST) PTEN

Fibro adipose vascular anomaly (FAVA) PIK3CA

Back to

overview

* Distinct from infantile hemangioma, from intramuscular common VM, PHOST/AST, FAVA and AVM

some lesions may be associated with thrombocytopenia and/or consumptive coagulopathy see details

Type Alt

for previous

view

Causal genes in blue

"Angiomatosis" of soft tissue (AST) (Rao and Weiss 1992)

A not-uncommon multi-tissular anomaly

associating fat, fibrosis, and vessels,

predominantly venous

Diagnosis based on a constellation of findings

multinodular stellate lesion

veins with thick walls fissures and pads

veins with pulmonary alveolar shape

thick onion-bulb vessels

lymphatic vessels

lymphocyte aggregates

bone foci

pulmonary alveolar shape or "cavernous"

bonelymphocyte aggregates myxoid backgroundsmooth m. bundles

radiating slits

Am J Surg Pathol 2012

Am J Surg Pathol 2012

J Pediatr Orthop 2014

Luks VL, et al.

Lymphatic and other vascular

malformative/overgrowth

disorders are caused by

somatic mutations in PIK3CA.

J Pediatr 2015

A series of vascular lesions with features of AST

– all with anomalies of PIK3CA or PTEN

– a majority of PIK3CA anomaly

– a minority of patiens with PTEN germline mutation

Boccara O, et al.

“PTEN hamartoma of soft tissue” may also be related to PIK3CA mutations.

22nd ISSVA Workshop. Amsterdam, May 29- June 1st; 2018

The histologically defined

angiomatosis of soft tissue (AST)

seems to correspond two different clinical entities

PTEN hamartoma of soft tissue (PHOST)

and fibro adipose vascular anomalie (FAVA)

• A diagnosis of AST should prompt testing for

PTEN germline mutation or PIK3CA mosaicism

– PTEN patients are at risk for cancer

– Targeted therapies for PIK3CA lesions exist

2018

2014

Tennant et al. Pediatr Dermatol 2006

Trindale et al. J Cutan Pathol 2013

Verrucous venous malformationformerly

verrucous hemangioma

• congenital lesion (affecting mainly the extremities)

• proportionate growth

• no change in shape and contours

• increase in thickness with increase

of hyperkeratosis

• no regression

• deep and lateral components

Superficial thin-walled dilate vessels

Lobulate capillary aggregates in subcutis

Glut-1

expression

Glut1

Verrucous venous malformation vs.

Angiokeratoma (circumscriptum)

• AK limited to the papillary dermis

• no reported expression of Glut-1

• frequent expression of lymphatic markers (at least focally)

• possibly related to – hyperkeratotic capillary-lymphatic malformations

– hyperkeratotic venous or veno-lymphatic malformations

– vascular skin lesions in patients with CCM

Trindade et al. J Cutan Pathol 2013

Trindade et al. Am J Dermatopathol. 2014

Skin lesions in a

patient with CCM

capillary-lymphatic malformation

in Klippel-Trenaunay syndrome

ISSVA classification for vascular anomalies

Provisionally unclassified vascular anomalies

Intramuscular hemangioma *

Angiokeratoma

Sinusoidal hemangioma

Acral arteriovenous "tumour"

Multifocal lymphangioendotheliomatosis with thrombocytopenia / cutaneovisceral

angiomatosis with thrombocytopenia (MLT/CAT)

PTEN (type) hamartoma of soft tissue / "angiomatosis" of soft tissue (PHOST) PTEN

Fibro adipose vascular anomaly (FAVA) PIK3CA

Back to

overview

* Distinct from infantile hemangioma, from intramuscular common VM, PHOST/AST, FAVA and AVM

some lesions may be associated with thrombocytopenia and/or consumptive coagulopathy see details

Type Alt

for previous

view

Causal genes in blue