Vascular tumors

2022-03-02   Paola Dal Cin 

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)



Vascular tumors are a diverse group of neoplasms, ranging from benign, self-limited neoplasms to highly aggressive malignancies. Recent advances in our understanding of tumour genetics have led to refine tumor classification system, to guide the development of reliable surrogate immunohistochemical markers and to help recognize potential therapeutic targets in patients with vascular malignancies. 1-3

Vascular tumoursGenetic event(s)
HemangiomaSingle cases with simple chromosomal aberrations which sometimes generate fusion genes. 4 Recurrent GNAQ/GNA14/ GNA11mutations in the majority of the very common cherry hemangioma. 5 GNA14 the most commonly mutated gene in vascular tumors. EWSR1::NFATC1 fusion has been reported in a few vascular malformations /hemangiomas . 6
Recurrent somatic mutations in IDH1 and IDH2 have been identified in a subset of sporadic spindle cell hemangioma (SCHs) and in SCHs from patients with Maffucci syndrome OMIM:614569 7
Anastomosing hemangiomaActivating hotspot mutations in GNAQ, GNA14 or GNA11,8 similar to the one in hepatic small vessel neoplasms. 9
Epithelioid hemangioma (EH)WWTR1::FOS mainly, other FOS partners MBLN1, VIM,lincRNand LMNA, rarely, WWRT1 and SEDT1B. 10 FOSB::ZFP36 often , or rarely WWTR1::FOSB or ACTB::FOSB. 11
Novel GATA6::FOX01 fusion in a subset of EH,mainly in skin, and head and neck locations. 12
Lymphangioma and lymphangiomatosisSomatic PIK3CA mutations in isolated lymphatic malformation (LM) and disorders in which LM is a component feature, 13 as CLOVES syndrome OMIM:612918, Klippel-Trenaunay syndrome OMIM:14900 and in patient with patients with fibro-adipose vascular anomaly (FAVA). 14
Tufted angioma and kaposiform hemangioendotheliomaSomatic activating GNA14 mutations have been reported. 15
Retiform hemangioendothelioma (RHE)MAML2::YAP1 fusions, 16 but also YAP1 rearrangements. 16
Papillary intralymphatic angioendotheliomaNo specific genetic findings so far
Composite hemangioendothelioma (CHE)Mainly MAML2 ::YAP1 fusions; 16 single cases with either PTBP1::MAML2 or EPC1::PCH2 in neuroendocrine variant. 16,17
Kaposi sarcoma (KP)Gain at 11q13 , including both FGF3 and FGF4.18
Copy number varations of chr. 14, 1, 21 and X in more advance lesions.19
Pseudomyogenic hemangioendothelioma (PSHE)t(7;19)(q22;q13) associated with SERPINE1::FOSB fusion. 20,21
ACTB::FOSB, more present in solitary lesions 22. Single case with WWTR1::FOSB 23 , CLTC::FOSB 24 and EGFL7::FOSB 25
Epithelioid hemangioendothelioma (EHE)t(1;3)(p36;q25) associated with WWTR1:: CAMTA1. 26-29 Variant WWTR1 fusions have been reported , which appears to have predilection for the heart. 30 YAP1::TFE3 gene fusion with distinctive features and more favorable outcome and leading to TFE3 overexpression. 29,31,32
Angiosarcoma (AS)Complex genetic profile much more common in secondary than promary ASs. 33 MYC amplification (up-regulates the miR17-92 cluster with/without FLT4 amplification, in radiation and lymphedema-associated ASs. 34,35
PLCG1 ,KDR and PTPRB mutations with/or without MYC amplification. 36,37 More frequently reported in primary mammary ASs . 38 Other genetic alterations and mutations have been reported , but rarely fusions. 3
CIC alterations ( mutations and rearrangements) in 10% of primary AGs , associated with epithelioid morphology and young patient age. 37


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Paola Dal Cin

Vascular tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-03-02

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