Pericytic (perivascular) tumors

2022-02-18   Paola Dal Cin 

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 GT2. 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. 3,4,5,6,7

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 extrmities , malignant one in the viscera. 8,9 A t(1;5)(p13;q32), resulting in the fusion CARMN::NOTCH2 gene fusion ,has been described mainly in the upper digestive track .10,11
Abnormalities in NOTCH1–3 have only been rarely identified in non-glomus pericytic tumors.1 The common subungual GT subset lack any NOTCH gene rearrangements 2, suggesting an alternative pathogenesis. 2
Inactivating mutations of the glomulin (GLMN) gene, at 1p22.1, in familiar glomuvenous malformations OMIM:13800012; glomus tumors in neurofibromatosis type 1 (NF1) OMIM:162200 arise secondary to biallelic inactivation of the NF1 13
BRAF V600E mutation associated with malignant phenotype 9 and more rarely KRAS mutation.14
Clinical response to targeted BRAF inhibition. 15
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.16,17
Recurrent gene rearrangements in the SRF gene, with several gene partners RELA ,ICA1 and CITED1. 18,19,20,21 Othe gene fusions MTCH2::FNBP4 , FN1::TIMP1, COL4A1::VEGFD. 21
PDGFRB (p.Pro660Thr and p.Arg561Cys) germline mutation in Autosomal Dominant -Infantile myofibromatosis 22 OMIM:228550
Therapy with tyrosine kinase inhibitors including imatinib may be beneficial. 23,24
NOTCH3 germline familal myofibromatosis kindred 25OMIM:615293
Angioleiomyoma No consistent chromosoems aberrations so far reported , mainly losses of 13q, 6p,6q and 21q. 26,27 No PDGFRB mutations. 28,29
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. 30,31,32
Additional GLI1 fusions reported with ACTB, MALAT1 , PTCH1 or APOD, partner genes, or high-level GLI1amplification,with some some resemblance to pericytic/glomus tumors or myoepithelial tumors , but with metastatic disease. 4,5,7,33,34,35,36

Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
1317051902020What is new in pericytomatous, myoid, and myofibroblastic tumors?John I et al
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
4327983112021Novel APOD-GLI1 rearrangement in a sarcoma of unknown lineage.Lopez-Nunez O et al
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
7346432882022Primary cutaneous epithelioid mesenchymal neoplasm with ACTB-GLI1 fusion: a case report.Rollins BT et al
8239999362013Novel MIR143-NOTCH fusions in benign and malignant glomus tumors.Mosquera JM et al
9288348102017BRAF V600E Mutations Occur in a Subset of Glomus Tumors, and Are Associated With Malignant Histologic Characteristics.Karamzadeh Dashti N et al
10265040452015Translocation (1;5) in a Glomus Tumor.Nishio J et al
11342451962021CARMN-NOTCH2 fusion transcript drives high NOTCH2 expression in glomus tumors of the upper digestive tract.Girard N et al
12238019312013Genotypes and phenotypes of 162 families with a glomulin mutation.Brouillard P et al
13197380422009Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association.Brems H et al
14223178872012BRAF and KRAS mutations in sporadic glomus tumors.Chakrapani A et al
15305560472018Sporadic Malignant Glomus Tumor of the Brachial Plexus With Response to Targeted Therapy Directed Against Oncogenic BRAF.Cuviello A et al
16283348762017PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis.Arts FA et al
17310176432019Association of PDGFRB Mutations With Pediatric Myofibroma and Myofibromatosis.Dachy G et al
18282488152017Recurrent SRF-RELA Fusions Define a Novel Subset of Cellular Myofibroma/Myopericytoma: A Potential Diagnostic Pitfall With Sarcomas With Myogenic Differentiation.Antonescu CR et al
19314789432020Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential For Malignant Behavior.Suurmeijer AJ et al
20330215232020SRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular Tumors.Karanian M et al
21338306702021Novel COL4A1-VEGFD gene fusion in myofibroma.Dachy G et al
22237315372013A recurrent PDGFRB mutation causes familial infantile myofibromatosis.Cheung YH et al
23312910542019PDGRFB mutation-associated myofibromatosis: Response to targeted therapy with imatinib.Weller JM et al
24316453462019Novel PDGFRB rearrangement in multifocal infantile myofibromatosis is tumorigenic and sensitive to imatinib.Hassan M et al
2523731541990Non-selenium glutathione peroxidase without glutathione S-transferase activity from bovine ciliary body.Shichi H et al
2629173331989Cytogenetic abnormalities in an angioleiomyoma.Nilbert M et al
27204715202010Angioleiomyoma: a benign tumor with karyotypic aberrations.Welborn J et al
28235179222013Mediator complex subunit 12 exon 2 mutation analysis in different subtypes of smooth muscle tumors confirms genetic heterogeneity.de Graaff MA et al
29277760102017Recurrent Somatic PDGFRB Mutations in Sporadic Infantile/Solitary Adult Myofibromas But Not in Angioleiomyomas and Myopericytomas.Agaimy A et al
30151113112004Activation 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
31155555712004Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma with t(7;12).Dahlén A et al
32321320202020An Unbalanced Chromosome Translocation Between 7p22 and 12q13 Leads to ACTB-GLI1 Fusion in Pericytoma.Panagopoulos I et al
33293093072018A 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
34311899982019GLI1-amplifications expand the spectrum of soft tissue neoplasms defined by GLI1 gene fusions.Agaram NP et al
35319349162020Head and Neck Mesenchymal Neoplasms With GLI1 Gene Alterations: A Pathologic Entity With Distinct Histologic Features and Potential for Distant Metastasis.Xu B et al
36340407022021Plexiform 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/pericytic-(perivascular)-tumors