Vascular tumors

2022-03-02   Paola Dal Cin 

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

Classification

Definition

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

Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
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4325765832020Fusion of the COL4A5 Gene With NR2F2-AS1 in a Hemangioma Carrying a t(X;15)(q22;q26) Chromosomal Translocation.Panagopoulos I et al
5311899942019High frequency of GNA14, GNAQ, and GNA11 mutations in cherry hemangioma: a histopathological and molecular study of 85 cases indicating GNA14 as the most commonly mutated gene in vascular neoplasms.Liau JY et al
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13256811992015Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA.Luks VL et al
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18107868112000FGF4 and INT2 oncogenes are amplified and expressed in Kaposi's sarcoma.Kiuru-Kuhlefelt S et al
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23312431102019Fusion of the Genes WWTR1 and FOSB in Pseudomyogenic Hemangioendothelioma.Panagopoulos I et al
24327490392021A novel CLTC-FOSB gene fusion in pseudomyogenic hemangioendothelioma of bone.Bridge JA et al
25335506372021Novel EGFL7-FOSB fusion in pseudomyogenic haemangioendothelioma with widely metastatic disease.Hakar MH et al
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30321707682020Variant WWTR1 gene fusions in epithelioid hemangioendothelioma-A genetic subset associated with cardiac involvement.Suurmeijer AJH et al
31237372132013Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma.Antonescu CR et al
32268402652016Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements.Lee SJ et al
33197236552009KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors.Antonescu CR et al
34200081402010MYC high level gene amplification is a distinctive feature of angiosarcomas after irradiation or chronic lymphedema.Manner J et al
35209495682011Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypical vascular lesions.Guo T et al
36246331572014Recurrent PTPRB and PLCG1 mutations in angiosarcoma.Behjati S et al
37267358592016Recurrent CIC Gene Abnormalities in Angiosarcomas: A Molecular Study of 120 Cases With Concurrent Investigation of PLCG1, KDR, MYC, and FLT4 Gene Alterations.Huang SC et al
38321233052020Primary mammary angiosarcomas harbor frequent mutations in KDR and PIK3CA and show evidence of distinct pathogenesis.Beca F et al

External Links

Citation

Paola Dal Cin

Vascular tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-03-02

Online version: http://atlasgeneticsoncology.org/solid-tumor/208942/vascular-tumors