Neuromuscular Choristoma: Report of Five Cases With CTNNB1 Sequencing

Abstract

Neuromuscular choristoma (NMC) are lesions of the peripheral nervous system characterized by an admixture of skeletal muscle fibers and nerves fascicles that are frequently associated with desmoid fibromatosis (DF). Mutations in CTNNB1, the gene for β-catenin protein, are common in DF and related to its pathogenesis. They are restricted to exon 3, with 3 point mutations: T41A, S45F, and S45P. To understand the pathogenesis of NMC, we tested CTNNB1 status in 5 cases of NMC whether or not they were associated with DF. The screening of mutations in CTNNB1 gene was based on amplicon deep sequencing using the ION Proton platform. Three patients had the S45F mutation; in 2 the mutation was common to both lesions and in one the DF was wild type while the NMC had the S45F mutation. One patient had a T41A mutation in the NMC and no associated DF. In the last patient, the DF lesion had a T41A mutation; there was no lesion with the S45P mutation. The presence of similar CTNNB1 mutations in NMC/DF-associated lesions and sporadic DF reinforces the relationship between both lesions and points to a common pathogenic mechanism.

Bioinformatic analysis and clinical diagnostic value of hsa_circ_0004099 in acute ischemic stroke

“…In addition, these four cancer pathways were jointly enriched in four genes, CTNNB1, TCF7L2, NRAS, and KRAS, mainly involved in cell proliferation. CTNNB1 is a gene encoding the β-catenin protein [27]. Neutrophils transcriptionally upregulate CTNNB1 expression to compensate for Mdm2/p53-mediated β-catenin degradation induced by exposure to ischemic neurons [28].…”

Multifocal Desmoid-Type Fibromatosis: Case Series and Potential Relationship to Neuronal Spread

“…In one report of seven NMC-DTF cases, six had an S45X mutation (five S45F and one S45P), and one had a T41A mutation [18]. In a report of five cases of NMC, three had a S45F mutation, and two T41A [14]. In general, ~30% of sporadic DTF cases have a T41A mutation [6,[24][25][26].…”

“…The neural spread of DTF is reminiscent of NMC, a peripheral nerve malformation. NMC is frequently associated with aggressive fibromatosis (NMC-DTF), a rare disease of unclear pathogenesis that also frequently bears a CTNNB1 mutation [14][15][16]18,19]. This raises the question of whether DTF spread along nerves could appear as distinct multifocal lesions while actually being contiguous.…”

“…NMC is a developmental lesion in which mature skeletal muscle cells, or rarely smooth muscle cells, infiltrate and enlarge peripheral nerves, typically of large nerves or plexuses, but also cranial nerves [14][15][16][18][19][20][21][22][23]. NMC is quite rare, and in some cases, DTF arises in the NMC lesion (NMC-DTF).…”

“…We report three cases that initially appeared to be multifocal sporadic DTF, two of which were later felt to reflect "subclinical" disease spread along nerves, suggesting they reflected a single atypical extensive tumor rather than true multifocal disease. The relationship of these cases to neuromuscular choristoma (NMC) [14][15][16] is discussed. The third case was thought to represent true multifocal tumor development, although possibly via "seeding" from previous surgery.…”