Vascular tumors
2022-03-02 Paola Dal Cin, PhD Affiliation1.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 tumours | Genetic event(s) | ||
|---|---|---|---|
| Hemangioma | Single 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 hemangioma | Activating 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 lymphangiomatosis | Somatic 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 hemangioendothelioma | Somatic activating GNA14 mutations have been reported. 15 | ||
| Retiform hemangioendothelioma (RHE) | MAML2::YAP1 fusions, 16 but also YAP1 rearrangements. 16 | ||
| Papillary intralymphatic angioendothelioma | No 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 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 30762622 | 2019 | Epithelioid Vascular Tumors: A Review. | Shon W et al |
| 2 | 31463731 | 2020 | What is new in endothelial neoplasia? | Papke DJ Jr et al |
| 3 | 34958509 | 2022 | The genetics of vascular tumours: an update. | Torrence D et al |
| 4 | 32576583 | 2020 | Fusion of the COL4A5 Gene With NR2F2-AS1 in a Hemangioma Carrying a t(X;15)(q22;q26) Chromosomal Translocation. | Panagopoulos I et al |
| 5 | 31189994 | 2019 | High 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 |
| 6 | 34081036 | 2021 | Expanding the Spectrum of EWSR1-NFATC2-rearranged Benign Tumors: A Common Genomic Abnormality in Vascular Malformation/Hemangioma and Simple Bone Cyst. | Ong SLM et al |
| 7 | 22057234 | 2011 | Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. | Pansuriya TC et al |
| 8 | 31707589 | 2020 | GNA11 joins GNAQ and GNA14 as a recurrently mutated gene in anastomosing hemangioma. | Liau JY et al |
| 9 | 29975248 | 2018 | Frequent GNAQ and GNA14 Mutations in Hepatic Small Vessel Neoplasm. | Joseph NM et al |
| 10 | 32948323 | 2021 | Intravascular epithelioid haemangioma of deep soft tissue with novel SETD1B-FOSB gene rearrangement. | Ooi LY et al |
| 11 | 25043949 | 2014 | ZFP36-FOSB fusion defines a subset of epithelioid hemangioma with atypical features. | Antonescu CR et al |
| 13 | 25681199 | 2015 | Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA. | Luks VL et al |
| 14 | 24322574 | 2014 | Fibro-adipose vascular anomaly: clinical-radiologic-pathologic features of a newly delineated disorder of the extremity. | Alomari AI et al |
| 15 | 27476652 | 2016 | GNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation. | Lim YH et al |
| 16 | 32991341 | 2020 | Recurrent YAP1 and MAML2 Gene Rearrangements in Retiform and Composite Hemangioendothelioma. | Antonescu CR et al |
| 17 | 28731049 | 2017 | Composite hemangioendothelioma with neuroendocrine marker expression: an aggressive variant. | Perry KD et al |
| 18 | 10786811 | 2000 | FGF4 and INT2 oncogenes are amplified and expressed in Kaposi's sarcoma. | Kiuru-Kuhlefelt S et al |
| 19 | 16954721 | 2006 | CGH of microdissected Kaposi's sarcoma lesions reveals recurrent loss of chromosome Y in early and additional chromosomal changes in late tumour stages. | Pyakurel P et al |
| 20 | 21536240 | 2011 | Translocation t(7;19)(q22;q13)−a recurrent chromosome aberration in pseudomyogenic hemangioendothelioma? | Trombetta D et al |
| 21 | 24374978 | 2014 | A novel SERPINE1-FOSB fusion gene results in transcriptional up-regulation of FOSB in pseudomyogenic haemangioendothelioma. | Walther C et al |
| 22 | 30256258 | 2018 | Expanding the Spectrum of Genetic Alterations in Pseudomyogenic Hemangioendothelioma With Recurrent Novel ACTB-FOSB Gene Fusions. | Agaram NP et al |
| 23 | 31243110 | 2019 | Fusion of the Genes WWTR1 and FOSB in Pseudomyogenic Hemangioendothelioma. | Panagopoulos I et al |
| 24 | 32749039 | 2021 | A novel CLTC-FOSB gene fusion in pseudomyogenic hemangioendothelioma of bone. | Bridge JA et al |
| 25 | 33550637 | 2021 | Novel EGFL7-FOSB fusion in pseudomyogenic haemangioendothelioma with widely metastatic disease. | Hakar MH et al |
| 26 | 11342786 | 2001 | Gastric dysplasia: the Pavoda International Classification. | Robinson MJ et al |
| 27 | 21584898 | 2011 | A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. | Errani C et al |
| 28 | 21885404 | 2011 | Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. | Tanas MR et al |
| 29 | 31537895 | 2020 | Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets. | Rosenbaum E et al |
| 30 | 32170768 | 2020 | Variant WWTR1 gene fusions in epithelioid hemangioendothelioma-A genetic subset associated with cardiac involvement. | Suurmeijer AJH et al |
| 31 | 23737213 | 2013 | Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. | Antonescu CR et al |
| 32 | 26840265 | 2016 | Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements. | Lee SJ et al |
| 33 | 19723655 | 2009 | KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors. | Antonescu CR et al |
| 34 | 20008140 | 2010 | MYC high level gene amplification is a distinctive feature of angiosarcomas after irradiation or chronic lymphedema. | Manner J et al |
| 35 | 20949568 | 2011 | Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypical vascular lesions. | Guo T et al |
| 36 | 24633157 | 2014 | Recurrent PTPRB and PLCG1 mutations in angiosarcoma. | Behjati S et al |
| 37 | 26735859 | 2016 | Recurrent 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 |
| 38 | 32123305 | 2020 | Primary mammary angiosarcomas harbor frequent mutations in KDR and PIK3CA and show evidence of distinct pathogenesis. | Beca F et al |
Citation
Paola Dal Cin, PhD
Vascular tumors
Atlas Genet Cytogenet Oncol Haematol. 2022-03-02
Online version: http://atlasgeneticsoncology.org/solid-tumor/208942/vascular-tumors
