Smooth Muscle Tumors

2022-03-01 Paola Dal Cin, PhD Affiliation

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

Classification

Definition

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 tumours	Genetic 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

Article Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	24384850	2014	Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis.	Miettinen M et al
2	30271265	2018	Benign Smooth Muscle Tumors (Leiomyomas) of Deep Somatic Soft Tissue.	McCarthy AJ et al
3	28591699	2017	Genetic heterogeneity in leiomyomas of deep soft tissue.	Panagopoulos I et al
4	23222489	2013	MED12 mutations in leiomyosarcoma and extrauterine leiomyoma.	Ravegnini G et al
5	24196187	2014	MED12 exon 2 mutations in uterine and extrauterine smooth muscle tumors.	Schwetye KE et al
6	25621995	2015	Novel KAT6B-KANSL1 fusion gene identified by RNA sequencing in retroperitoneal leiomyoma with t(10;17)(q22;q21).	Panagopoulos I et al
7	25875009	2015	Fusion of the genes EWSR1 and PBX3 in retroperitoneal leiomyoma with t(9;22)(q33;q12).	Panagopoulos I et al
8	32358363	2020	Epstein-Barr virus associated hepatic smooth muscle tumor in a patient with acquired immunodeficiency syndrome: A case report.	Zhou Q et al
9	25027306	2014	Clinico-pathological characteristics of different types of immunodeficiency-associated smooth muscle tumours.	Hussein K et al
10	28112205	2017	A human immunodeficiency syndrome caused by mutations in CARMIL2.	Schober T et al
11	29535735	2018	Epstein-Barr Virus(+) Smooth Muscle Tumors as Manifestation of Primary Immunodeficiency Disorders.	Magg T et al
12	9713368	1998	Inflammatory leiomyosarcoma may be characterized by specific near-haploid chromosome changes.	Dal Cin P et al
13	28884746	2018	Inflammatory leiomyosarcoma is a distinct tumor characterized by near-haploidization, few somatic mutations, and a primitive myogenic gene expression signature.	Arbajian E et al
14	33318583	2021	"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
15	23019412	2012	Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.	Nord KH et al
16	29100075	2017	Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.
17	29220301	2018	Soft Tissue and Uterine Leiomyosarcoma.	George S et al
18	29321523	2018	Integrative genomic and transcriptomic analysis of leiomyosarcoma.	Chudasama P et al
19	26541895	2016	Targeted exome sequencing profiles genetic alterations in leiomyosarcoma.	Agaram NP et al
20	33283135	2020	Clinical Outcome of Leiomyosarcomas With Somatic Alteration in Homologous Recombination Pathway Genes.	Rosenbaum E et al

External Links

Citation

Paola Dal Cin, PhD

Smooth Muscle Tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-03-01