Pericytic and perivascular tumors
2026-10-21 Paola Dal Cin, PhD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
Keywords
Cutaneous soft tissue neoplasms. glomus tumor , myopericytoma, myofibroma, myofibromatosis , angioleiomyoma, PDGFRB, CARMN,Classification
Definition
Cutaneous pericytic and perivascular neoplasms include glomus tumor (GT), myopericytoma (MP), myofibroma (MF) /myofibromatosis , and angioleiomyoma (AL), but these tumors represent a morphological continuum, with some cases showing overlapping features. PDGFRB or NOTCH3 mutations are not useful for subclassifying members of the pericytic tumor family since they are detectable in a wider range of pericytic tumors, and their combined tumors. 1 The presence of CARMN fusions and PDGFRB mutations was mutually exclusive in both myopericytomas and globus tumors, suggesting that they possess key molecular similarities and are generally genetically distinct from angioleiomyoma. 2
The gain-of-function of PDGFRB mutations may respond to tyrosine kinase inhibitors providing therapeutic options for progressive and/or multicentric disease. 3
A rare subset of tumors with pericytic features harboring t(7;12)(p22;q13) associated to with a ACTB::GLI1 fusion. 4 However, recent study showed that tumors with this rearrangement or other variant GLI1 rearrangement may have variable morphology and immunohistochemical phenotype with inconsistent myopericytic characteristics and a propensity for metastasis, 5,6 raising questions regarding the most appropriate classification of these neoplasms.
| Pericytic and perivascular tumors | ||
|---|---|---|
| Benign pericytic and perivascular neoplasms | Gentic events | |
| Glomus tumor | Glomus tumors (GTs) are mainly benign lesions most frequently located in the distal extremities, particularly in the subungual regions of the hands and feet. | |
| Multiple GTs are often found in the children and are due to the mutation in GLMN on chromosome 1p21-22, which shows an autosomal dominant pattern of inheritance,7 and rarely associated with with neurofibromatosis type 1. 8 Rearrangements involving NOTCH genes, with MIR143::NOTCH2 associated with t(1;15)(p13;q32)9 been the most common fusion reported in sporadic benign and malignant cases, 2,10 While NOTCH1 and NOTCH rearrangements were also recognized in a smaller number of benign glomus tumors. 11 BRAF V600E mutation was also detected in a minority of cases of glomus tumors, all of which were malignant. 12 PDGFRB and NOTCH3 mutations were also detected . 1,2 | ||
| Myopericytoma | Most lesions are benign solitary dermal-based or subcutaneous, while deep lesions are rare. PDGFRB and NOTCH3 mutations have been reported,1,13 and also rarely KRAS.2 BRAF V600E mutation was also detetected in a small subset of such indole but locally aggressive perivascual proliferation. 14 CARMN::TXK fusion was the most freqent rearrangement observed, compared with CARMN::NOTCH2 previously known as MIR143::NOTCH2 .2 | |
| Myofibroms and myofibromatosis | Solitary lesions originate in the skin or subcutis of the head and neck, upper extremities, or trunk. PDGFRB mutations have been reorted in both sporadic infantile and adult myofibroma (MFs). 15,16 Germline mutations in PDGFRB and rarely NOTCH3 have been detected in the familial disease.17,18 | |
| A rare and distinctive subset of cellular myofibromas predominantly occurring in children has been newly characterized by SRF fusions mainly with RELA as gene partner , and less coomonly C3orf62, ICA1I, STAT6, CITED1, CITED, NFKBIE, and NCOA2 .19,20 | ||
| Angioleiomyoma | Solitary benign lesions arise in the skin and subcutis of the extremities (particularly around the knee). Chromosomal imbalances have been reported in 9 angioleiomyomas by karyotype and comparative genomic hybridization. 21 A single case angioleiomyoma showed NOTCH2 fusion, 11 and rarely cases with mutations of NOTCH3, PDGFRB and PIK3CA were also reported. 1,2 So far MED12 mutations were not detected. 22 | |
| Recently a CARMN::TXK fusion was reported associated with a t(4;5)(p12;q32) , already previously described by karyotype 23, as well as a four-way translocation, t(X;3;4;16)(q22;p11;q11;p13) with rearrangement of MYH11 at 16p13 with intergenic sequences from Xq22, resulting in enhanced IRS4 expression.21 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 36788105 | 2023 | PDGFRB and NOTCH3 Mutations are Detectable in a Wider Range of Pericytic Tumors, Including Myopericytomas, Angioleiomyomas, Glomus Tumors, and Their Combined Tumors. | Iwamura R et al |
| 2 | 42140550 | 2026 | CARMN fusions and PDGFRB mutations highlight key differences among cutaneous tumors with myopericytic differentiation. | Velasco-Herrera MDC et al |
| 3 | 31291054 | 2019 | PDGRFB mutation-associated myofibromatosis: Response to targeted therapy with imatinib. | Weller JM et al |
| 4 | 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 |
| 5 | 31567194 | 2019 | Pericytoma With t(7;12) and ACTB-GLI1 Fusion: Reevaluation of an Unusual Entity and its Relationship to the Spectrum of GLI1 Fusion-related Neoplasms. | Kerr DA et al |
| 6 | 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 |
| 7 | 15689436 | 2005 | Four common glomulin mutations cause two thirds of glomuvenous malformations ("familial glomangiomas"): evidence for a founder effect. | Brouillard P et al |
| 8 | 25426397 | 2014 | Glomus tumors and neurofibromatosis: a newly recognized association. | Harrison B et al |
| 9 | 26504045 | 2015 | Translocation (1;5) in a Glomus Tumor. | Nishio J et al |
| 10 | 32604167 | 2020 | A Molecular Reappraisal of Glomus Tumors and Related Pericytic Neoplasms With Emphasis on NOTCH-gene Fusions. | Agaram NP et al |
| 11 | 23999936 | 2013 | Novel MIR143-NOTCH fusions in benign and malignant glomus tumors. | Mosquera JM et al |
| 12 | 28834810 | 2017 | BRAF V600E Mutations Occur in a Subset of Glomus Tumors, and Are Associated With Malignant Histologic Characteristics. | Karamzadeh Dashti N et al |
| 13 | 28505006 | 2017 | Myopericytomatosis: Clinicopathologic Analysis of 11 Cases With Molecular Identification of Recurrent PDGFRB Alterations in Myopericytomatosis and Myopericytoma. | Hung YP et al |
| 14 | 25063326 | 2014 | Role of BRAFV600E in the first preclinical model of multifocal infiltrating myopericytoma development and microenvironment. | Sadow PM et al |
| 15 | 27776010 | 2017 | Recurrent Somatic PDGFRB Mutations in Sporadic Infantile/Solitary Adult Myofibromas But Not in Angioleiomyomas and Myopericytomas. | Agaimy A et al |
| 16 | 31566039 | 2020 | A Distinctive Genomic and Immunohistochemical Profile for NOTCH3 and PDGFRB in Myofibroma With Diagnostic and Therapeutic Implications. | Koo SC et al |
| 17 | 23731542 | 2013 | Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. | Martignetti JA et al |
| 18 | 23865785 | 2013 | Mutations in PDGFRB and NOTCH3 are the first genetic causes identified for autosomal dominant infantile myofibromatosis. | Lee JW 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 | 37245628 | 2023 | Cellular myofibromas with SRF fusions: clinicopathological and molecular study of 3 cases of a rare entity and a potential mimic of sarcoma. | Papa B et al |
| 21 | 37889065 | 2023 | Pathogenetic Dichotomy in Angioleiomyoma. | Panagopoulos I et al |
| 22 | 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 |
| 23 | 20471520 | 2010 | Angioleiomyoma: a benign tumor with karyotypic aberrations. | Welborn J et al |
Citation
Paola Dal Cin, PhD
Pericytic and perivascular tumors
Atlas Genet Cytogenet Oncol Haematol. 2026-10-21
Online version: http://atlasgeneticsoncology.org/solid-tumor/209392
