Smooth Muscle Tumors

2022-03-01   Paola Dal Cin 

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



They may occur in any body parts where smooth muscles are present, and are  considered an essentially dichotomous group composed of benign leiomyomas and malignant leiomyosarcomas.1,2

Smooth mucle tumoursGenetic Event(s)
Leiomyoma Similar aberations in uterine leiomyoma e.g. 12q14.3 HMGA2 , 8q12 PLAG1, del(7q) rearrangement,expressing MED12 but none of them had MED12 exon 2 mutation. 3
MED12 exon 2 mutations .4,5
Single fusion reports in deep seated lesions: t(10;17)(q22;q21) associated to KAT6B::KANSL1; 6 t(9;22)(q33;q12) associated to EWSR1::PBX3. 7
EBV-associated smooth muscle tumours (EBV-SMT)Rare Epstein-Barr virus (EBV)+ smooth muscle tumours arising in three distinct clinical settings related to immunosuppression: (i) HIV infection, 8 (ii) solid organ transplant recipients,9 and (iii) congenital immunodeficiency disorders. 10,11 In situ hybridization for Epstein-Barr encoding region (EBER) , the most reliable confirmatory test in the absence of PCR-based methodologies. 9
Inflammatory leiomyosarcoma (ILMS)Near-haploid karyotype with/without whole genome doubling.12,13 Similarr morphologic and genetic features have been reported in "histiocyte-rich rhabdomyoblastic tumor".14
LOH of most chromosomes, except for chrs 5 and 22, and often for chrs. 18, 20 and 22.15
NF1 mutations in a subset of cases. 13
Leiomyosarcoma (LMS)Chromosomal instability: complex karyotype, whole-genome duplication and chromosomal losses affecting tumor suppressor genes such as TP53, RB1, and PTEN.16,17 Near-universal biallelic TP53 and RB1 inactivation.18 Amplification of myocardin MYOCD gene in a subset of cases.19
Alternative telomere lengthening (78%) and recurrent alterations in telomere maintenance genes such as ATRX,RBL2, and SP100.18
Genomic signatures of homologous recombination deficiency.18,20
Genetic predisposition: Li-Fraumeni syndrome OMIM:151623 and hereditary retinoblastoma OMIM:180200


Reference NumberPubmed IDLast YearTitleAuthors
1243848502014Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis.Miettinen M et al
2302712652018Benign Smooth Muscle Tumors (Leiomyomas) of Deep Somatic Soft Tissue.McCarthy AJ et al
3285916992017Genetic heterogeneity in leiomyomas of deep soft tissue.Panagopoulos I et al
4232224892013MED12 mutations in leiomyosarcoma and extrauterine leiomyoma.Ravegnini G et al
5241961872014MED12 exon 2 mutations in uterine and extrauterine smooth muscle tumors.Schwetye KE et al
6256219952015Novel KAT6B-KANSL1 fusion gene identified by RNA sequencing in retroperitoneal leiomyoma with t(10;17)(q22;q21).Panagopoulos I et al
7258750092015Fusion of the genes EWSR1 and PBX3 in retroperitoneal leiomyoma with t(9;22)(q33;q12).Panagopoulos I et al
8323583632020Epstein-Barr virus associated hepatic smooth muscle tumor in a patient with acquired immunodeficiency syndrome: A case report.Zhou Q et al
9250273062014Clinico-pathological characteristics of different types of immunodeficiency-associated smooth muscle tumours.Hussein K et al
10281122052017A human immunodeficiency syndrome caused by mutations in CARMIL2.Schober T et al
11295357352018Epstein-Barr Virus(+) Smooth Muscle Tumors as Manifestation of Primary Immunodeficiency Disorders.Magg T et al
1297133681998Inflammatory leiomyosarcoma may be characterized by specific near-haploid chromosome changes.Dal Cin P et al
13288847462018Inflammatory leiomyosarcoma is a distinct tumor characterized by near-haploidization, few somatic mutations, and a primitive myogenic gene expression signature.Arbajian E et al
14333185832021"Inflammatory Leiomyosarcoma" and "Histiocyte-rich Rhabdomyoblastic Tumor": a clinicopathological, immunohistochemical and genetic study of 13 cases, with a proposal for reclassification as "Inflammatory Rhabdomyoblastic Tumor".Cloutier JM et al
15230194122012Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.Nord KH et al
16291000752017Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.
17292203012018Soft Tissue and Uterine Leiomyosarcoma.George S et al
18293215232018Integrative genomic and transcriptomic analysis of leiomyosarcoma.Chudasama P et al
19265418952016Targeted exome sequencing profiles genetic alterations in leiomyosarcoma.Agaram NP et al
20332831352020Clinical Outcome of Leiomyosarcomas With Somatic Alteration in Homologous Recombination Pathway Genes.Rosenbaum E et al


Paola Dal Cin

Smooth Muscle Tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-03-01

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