摘要：

目的: 总结具有杆状体结构的肌肉病的临床病理学特征及其鉴别诊断。方法与结果: 纳入2021年5月至2024年5月在北京大学第三医院经肌肉组织活检证实的22例具有杆状体结构的肌肉病患者, 最终诊断为先天性杆状体肌病3例（13.64%）、肌萎缩侧索硬化12例（54.54%）、肢带型肌营养不良症2例（9.09%）, 以及结蛋白病、腓骨肌萎缩症、非特异性肌炎、GRN基因变异的额颞叶痴呆、甲状腺功能减退性肌病各1例（4.55%）。改良Gomori三色染色可见肌浆内数量不等的颗粒状、杆状或片状紫红色物质。免疫组化染色肌收缩蛋白和（或）α-肌动蛋白阳性。超微结构观察, 部分具有杆状体超微结构特征。先天性杆状体肌病杆状体形态较典型且数量较多, 肌收缩蛋白和α-肌动蛋白均免疫阳性; 其他疾病除存在杆状体结构外, 固有病理改变各有特点, 肌萎缩侧索硬化常见神经源性肌萎缩, 结蛋白病肌纤维可见结蛋白异常聚集, 肌营养不良常见圆形萎缩、多量核内移、间质纤维化, 非特异性肌炎常见较明显的炎性细胞浸润等。因此, 杆状体肌病的诊断不能仅依靠HE染色和电子显微镜检查。全外显子组测序显示存在NEB基因变异（3例）、CAPN3基因杂合突变（1例）、DYSF基因变异（1例）、SH3TC2基因杂合突变（1例）、GRN基因变异（1例）和DES基因杂合突变（1例）。结论: 杆状体结构可见于多种肌肉病和神经系统变性疾病, 结合临床病理学特点有助于诊断杆状体肌病, 明确诊断依靠基因检测。

关键词: 肌病，杆状体, 免疫组织化学, 显微镜检查，电子，透射, 病理学, 诊断，鉴别

Abstract:

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-marietooth 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.

Key words: Myopathies, nemaline, Immunohistochemistry, Microscopy, electron, transmission, Pathology, Diagnosis, differential