The clinicopathological characteristics analysis and differential diagnosis of muscle disorder cases with nemaline⁃shaped structure

Objective Summarize the pathological and clinical characteristics of muscle disorder cases with nemaline⁃shaped structure, to improve the diagnosis and differential diagnosis of the disease. Methods and Results A total of 22 cases with nemaline⁃shaped structure underwent muscle biopsy were selected from May 2021 to May 2024. As to final diagnosis, there were 3 cases (13.64%) of congenital nemaline myopathy, 12 cases (54.54%) of amyotrophic lateral sclerosis (ALS), 2 cases (9.09%) of limb⁃girdle muscular dystrophy (LGMD), one case (1.45%) of desminopathy, one case (1.45%) of charcot⁃marie⁃tooth disease (CMT), one case (1.45%) of non⁃specific myositis, one case (1.45%) of frontotemporal dementia (FTO) caused by GRN, and one case (1.45%) of hypothyroid myopathy. The muscle biopsy of all 22 cases revealed various granular, rod⁃shape or flaky purplish⁃red depositions in the sarcoplasm as nemaline⁃shaped structure in modified Gomori trichrome (MGT) staining and positive immunohistochemistry staining of myotilin and/or α⁃actin. Under electron microscopy, some cases had the ultrastructural characteristics of nemaline body or nemaline⁃shaped structure. Muscle biopsy that confirmed congenital nemaline myopathy had more typical nemaline, besides myotilin and α⁃actin were both immunopositively. Besides nemaline myopathy, the pathological changes of other muscle diseases also had specific characteristics, such as neurogenic atrophy was often present in ALS; abnormal aggregation of desmin protein was often present in desminopathy; circular atrophy, large amount internalized nuclei and interstitial fibrosis were often present in LGMD; in addition, obvious inflammatory cell infiltration was common in non⁃specific myositis. Therefore, the diagnosis of nemaline myopathy could not be relied on HE staining and electron microscopy alone. Apart from 14 patients that diagnosed with ALS, non⁃specific myositis and hypothyroid myopathy, NEB gene mutation (3 cases), CAPN3 gene mutation (one case), DYSF gene mutation (one case), SH3TC2 gene mutation (one case), GRN gene mutation (one case), and DES gene heterozygous mutation (one case) were detected by whole exome sequencing (WES) in the remaining 8 cases. Conclusions Nemaline⁃shaped structure can appear in a variety of muscular disorder and neurodegenerative diseases. Combined with clinicopathological characteristics are contribute to recognize nemaline myopathy, and the genetic test by WES is strong evidence for nemaline myopathy.