Pericytic (perivascular) tumors

2022-02-18 Paola Dal Cin, PhD Affiliation

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

Classification

Definition

Pericytes are contractile cells that surround small blood vessel, that can differentiate along smooth muscle lineage (“myopericytes”) or exhibit a “glomoid” phenotypes .¹ Glomus tumor (GT), together with myofibroma (MF), myopericytoma (MP), and angioleiomyoma (AL) are members of the pericytic family. However, emerging genetic data across these neoplasms is dissimilar, arguing against a pathogenetically unified family: PDGFRB-mutant MF and MP and NOTCH–fusion-positive GT.² Recently, group of neoplasms with GLI1 rearrangements/amplification has been reported which show some resemblance to pericytic tumors, without specific immunophenotype. However, classification of this group of neoplasms remains challenging. ^3-7

Pericytic (perivascular) tumors	Genetics event(s)
Glomus tumors (GT)	NOTCH gene family rearrangement , with the most common alteration being NOTCH2::MIR143 gene fusion ; benign lesions mainly in soft tissue of the extimities , malignant one in the viscera ^8,9
	Abnormalities in NOTCH1–3 have only been rarely identified in non-glomus pericytic tumors ¹. The common subungual GT subset lack NOTCH-gene fusions suggesting an alternative pathogenesis ².
	Inactivating mutations of the glomulin (GLMN) gene, at 1p22.1, in familiar glomuvenous malformations OMIM:138000; ¹⁰ glomus tumors in neurofibromatosis type 1 (NF1) OMIM:162200 arise secondary to biallelic inactivation of the NF1 ¹¹
	BRAF V600E mutation associated with malignant phenotype ⁹ and more rarely KRAS mutation.¹²
	Clinical response to targeted BRAF inhibition.¹³
Myopericytoma(MP), incuding myofibroma (MF)	PDGFRB p.Asn666Lys most requent mutation in myopericytomatosis, low-level PDGFRB amplification} in a subset of both MPs and myopericytomatosis.^14,15
	Recurrent gene rearrangements in the SRF gene, with several gene partners RELA ,ICA1 and CITED1. ^16-18 Othe gene fusions MTCH2::FNBP , FN1::TIMP1, COL4A1::VEGFD ^18,19
	PDGFRB (p.Pro660Thr and p.Arg561Cys) germline mutation in Autosomal Dominant -Infantile myofibromatosis ²⁰ OMIM:228550
	Therapy with tyrosine kinase inhibitors including imatinib may be beneficial ^21,22
	NOTCH3 germline familal myofibromatosis kindred ²³OMIM:615293
Angioleiomyoma	No consistent chromosoems aberrations so far reported , mainly losses of 13q, 6p,6q and 21q.^24,25 No PDGFRB mutations. ^26,27
GLI1 rearrangement (emerging entity)	t(7;12)(p22;q13) associated with ACTB::GLI1 fusion defined an unusual subset of actin-positive, perivascular myoid tumors with benign course. ^28-30
	Additional GLI1 fusions reported with ACTB, MALAT1 , PTCH1 or APOD, partner genes, or high-level ampliﬁcations of the GLI1 locus,with some some resemblance to pericytic/glomus tumors or myoepithelial tumors , but with metastatic disease. ^4,5,7,31-34

Article Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	31705190	2020	What is new in pericytomatous, myoid, and myofibroblastic tumors?	John I et al
2	32604167	2020	A Molecular Reappraisal of Glomus Tumors and Related Pericytic Neoplasms With Emphasis on NOTCH-gene Fusions.	Agaram NP et al
3	31147874	2019	Pericytes in Sarcomas and Other Mesenchymal Tumors.	Chang L et al
4	32798311	2021	Novel APOD-GLI1 rearrangement in a sarcoma of unknown lineage.	Lopez-Nunez O et al
5	34779913	2022	GLI1-altered mesenchymal tumor: a clinicopathological and molecular analysis of ten additional cases of an emerging entity.	Liu J et al
6	34655412	2022	Epithelioid Soft Tissue Neoplasm of the Soft Palate with a PTCH1-GLI1 Fusion: A Case Report and Review of the Literature.	Klubíčková N et al
7	34643288	2022	Primary cutaneous epithelioid mesenchymal neoplasm with ACTB-GLI1 fusion: a case report.	Rollins BT et al
8	23999936	2013	Novel MIR143-NOTCH fusions in benign and malignant glomus tumors.	Mosquera JM et al
9	28834810	2017	BRAF V600E Mutations Occur in a Subset of Glomus Tumors, and Are Associated With Malignant Histologic Characteristics.	Karamzadeh Dashti N et al
10	23801931	2013	Genotypes and phenotypes of 162 families with a glomulin mutation.	Brouillard P et al
11	19738042	2009	Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association.	Brems H et al
12	22317887	2012	BRAF and KRAS mutations in sporadic glomus tumors.	Chakrapani A et al
13	30556047	2018	Sporadic Malignant Glomus Tumor of the Brachial Plexus With Response to Targeted Therapy Directed Against Oncogenic BRAF.	Cuviello A et al
14	28334876	2017	PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis.	Arts FA et al
15	31017643	2019	Association of PDGFRB Mutations With Pediatric Myofibroma and Myofibromatosis.	Dachy G et al
16	28248815	2017	Recurrent SRF-RELA Fusions Define a Novel Subset of Cellular Myofibroma/Myopericytoma: A Potential Diagnostic Pitfall With Sarcomas With Myogenic Differentiation.	Antonescu CR et al
17	31478943	2020	Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential For Malignant Behavior.	Suurmeijer AJ et al
18	33830670	2021	Novel COL4A1-VEGFD gene fusion in myofibroma.	Dachy G et al
19	33021523	2020	SRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular Tumors.	Karanian M et al
20	23731537	2013	A recurrent PDGFRB mutation causes familial infantile myofibromatosis.	Cheung YH et al
21	31291054	2019	PDGRFB mutation-associated myofibromatosis: Response to targeted therapy with imatinib.	Weller JM et al
22	31645346	2019	Novel PDGFRB rearrangement in multifocal infantile myofibromatosis is tumorigenic and sensitive to imatinib.	Hassan M et al
23	2373154	1990	Non-selenium glutathione peroxidase without glutathione S-transferase activity from bovine ciliary body.	Shichi H et al
24	2917333	1989	Cytogenetic abnormalities in an angioleiomyoma.	Nilbert M et al
25	20471520	2010	Angioleiomyoma: a benign tumor with karyotypic aberrations.	Welborn J et al
26	23517922	2013	Mediator complex subunit 12 exon 2 mutation analysis in different subtypes of smooth muscle tumors confirms genetic heterogeneity.	de Graaff MA et al
27	27776010	2017	Recurrent Somatic PDGFRB Mutations in Sporadic Infantile/Solitary Adult Myofibromas But Not in Angioleiomyomas and Myopericytomas.	Agaimy A et al
28	15111311	2004	Activation of the GLI oncogene through fusion with the beta-actin gene (ACTB) in a group of distinctive pericytic neoplasms: pericytoma with t(7;12).	Dahlén A et al
29	15555571	2004	Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma with t(7;12).	Dahlén A et al
30	32132020	2020	An Unbalanced Chromosome Translocation Between 7p22 and 12q13 Leads to ACTB-GLI1 Fusion in Pericytoma.	Panagopoulos I et al
31	29309307	2018	A Distinct Malignant Epithelioid Neoplasm With GLI1 Gene Rearrangements, Frequent S100 Protein Expression, and Metastatic Potential: Expanding the Spectrum of Pathologic Entities With ACTB/MALAT1/PTCH1-GLI1 Fusions.	Antonescu CR et al
32	31189998	2019	GLI1-amplifications expand the spectrum of soft tissue neoplasms defined by GLI1 gene fusions.	Agaram NP et al
33	31934916	2020	Head and Neck Mesenchymal Neoplasms With GLI1 Gene Alterations: A Pathologic Entity With Distinct Histologic Features and Potential for Distant Metastasis.	Xu B et al
34	34040702	2021	Plexiform fibromyxoma: Review of rare mesenchymal gastric neoplasm and its differential diagnosis.	Arslan ME et al

External Links

Citation

Paola Dal Cin

Pericytic (perivascular) tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-02-18

Online version: http://atlasgeneticsoncology.org/solid-tumor/208938/gene-fusions-explorer/gene-fusions-explorer/css/template-nav.css