Pericytic (perivascular) tumors

2022-02-18   Paola Dal Cin 

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



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) tumorsGenetics 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


Reference NumberPubmed IDLast YearTitleAuthors
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2326041672020A Molecular Reappraisal of Glomus Tumors and Related Pericytic Neoplasms With Emphasis on NOTCH-gene Fusions.Agaram NP et al
3311478742019Pericytes in Sarcomas and Other Mesenchymal Tumors.Chang L et al
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5347799132022GLI1-altered mesenchymal tumor: a clinicopathological and molecular analysis of ten additional cases of an emerging entity.Liu J et al
6346554122022Epithelioid Soft Tissue Neoplasm of the Soft Palate with a PTCH1-GLI1 Fusion: A Case Report and Review of the Literature.Klubíčková N et al
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9288348102017BRAF V600E Mutations Occur in a Subset of Glomus Tumors, and Are Associated With Malignant Histologic Characteristics.Karamzadeh Dashti N et al
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19330215232020SRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular Tumors.Karanian M et al
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21312910542019PDGRFB mutation-associated myofibromatosis: Response to targeted therapy with imatinib.Weller JM et al
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2323731541990Non-selenium glutathione peroxidase without glutathione S-transferase activity from bovine ciliary body.Shichi H et al
2429173331989Cytogenetic abnormalities in an angioleiomyoma.Nilbert M et al
25204715202010Angioleiomyoma: a benign tumor with karyotypic aberrations.Welborn J et al
26235179222013Mediator complex subunit 12 exon 2 mutation analysis in different subtypes of smooth muscle tumors confirms genetic Graaff MA et al
27277760102017Recurrent Somatic PDGFRB Mutations in Sporadic Infantile/Solitary Adult Myofibromas But Not in Angioleiomyomas and Myopericytomas.Agaimy A et al
28151113112004Activation 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
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30321320202020An Unbalanced Chromosome Translocation Between 7p22 and 12q13 Leads to ACTB-GLI1 Fusion in Pericytoma.Panagopoulos I et al
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Paola Dal Cin

Pericytic (perivascular) tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-02-18

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