Paediatric and Perinatal Pathology Update on vascular anomalies of childhood
ISSVA classification for vascular anomalies
Provisionally unclassified vascular anomalies
Michel Wassef M.D. Dept of pathology and vascular anomalies clinics Lariboisière Hospital Paris, France Back to Type Alt overview for previous ISSVA classification for vascular anomalies view
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
* 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
Causal genes in blue Intramuscular hemangioma
Correspond to capillary type and part of mixed types of WHO "intramuscular hemangioma" T1 T1 G
T1 T1 G fs
T2
Intramuscular (capillary) hemangioma vs. 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 Back to Type Alt overview for previous ISSVA classification for vascular anomalies view
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
* 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
Causal genes in blue Multifocal lymphangioendotheliomatosis with thrombocytopenia Cutaneovisceral angiomatosis with thrombocytopenia
• 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
North, Arch Dermatol 2004, Prasad, Pediatr Dev Pathol 2005 MLT /CAT
Prasad, Pediatr Dev Pathol 2005 MLT / CAT CD31
Yeung et al. J Am Acad Dermatol 2006 D2-40 MLT / CAT
CD31 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 Esparza JAAD 2012 LYVE1
D2-40 Back to Type Alt overview for previous ISSVA classification for vascular anomalies view
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
* 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
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" radiating slits
smooth m. bundles lymphocyte aggregates bone myxoid background 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 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
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 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 Verrucous venous malformation formerly 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 Tennant et al. Pediatr Dermatol 2006
• deep and lateral components
Trindale et al. J Cutan Pathol 2013 Superficial thin-walled dilate vessels Lobulate capillary aggregates in subcutis
Glut1
Glut-1 expression 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) Trindade et al. J Cutan Pathol 2013 Trindade et al. Am J Dermatopathol. 2014 • possibly related to – hyperkeratotic capillary-lymphatic malformations – hyperkeratotic venous or veno-lymphatic malformations – vascular skin lesions in patients with CCM
capillary-lymphatic malformation Skin lesions in a in Klippel-Trenaunay syndrome patient with CCM Back to Type Alt overview for previous ISSVA classification for vascular anomalies view
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
* 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
Causal genes in blue