3例Lafora病的临床病理和超微结构特征

Clinical pathology and ultrastructural features of 3 cases of Lafora disease

目的:Lafora病是一种罕见的遗传性神经退行性疾病,其病因、临床表现、检查与诊断等均具有一定的复杂性和特殊性。本研究基于一家系3例Lafora病皮肤活体组织检查(以下简称“活检”),探讨Lafora病的病理学、免疫组织化学和超微结构特征。方法:收集2022年3月经广州金域医学检验中心病理诊断、临床确诊的3例Lafora病患者的临床资料、皮肤活体组织病理和超微病理特征及遗传学改变。3位患者为同一家系,其中男1例,女2例,均经皮肤活检证实。皮肤活检均取自患者右侧腋窝皮肤,常规标本经中性甲醛固定,行苏木素-伊红(Hematoxylin and Eosin,HE)染色、过碘酸希夫染色(periodic acid Schiff staining,PAS)、淀粉酶消化-过碘酸希夫染色(amylase digestion-periodic acid Schiff staining,D-PAS)、阿尔新蓝-过碘酸希夫染色(periodic acid Schiff and alcian blue staining,AB-PAS)及α1-抗胰蛋白酶(alpha 1-antitrypsin,α1-ATT)免疫组织化学染色。对于先症者,同时取右侧腋窝皮肤标本,用2.5%戊二醛固定液固定,半薄切片经甲苯胺蓝染色定位汗腺,超薄切片在透射电镜下观察超微结构。结果:3例皮肤活检光镜下组织病理学变化均轻微,HE染色仅表现为个别小汗腺导管细胞和大汗腺肌上皮细胞胞质空泡化,可见苍白色圆形包涵体,即Lafora小体。PAS、DPAS、AB-PAS示Lafora小体阳性,甲苯胺蓝染色不显色,免疫组织化学染色示Lafora小体不表达α1-AAT。电镜下小汗腺导管上皮、大汗腺肌上皮细胞可见胞质内包涵体,小汗腺周围间质成纤维细胞可见核内包涵体。结论:Lafora病皮肤病变轻微,组织学诊断困难,PAS和电镜检查发现Lafora小体具有重要诊断价值。完整详细的病史、家族史结合临床检查,特别是病理及基因检测可以帮助尽早诊断。

Objective:Lafora disease is a rare genetic neurodegenerative disorder characterized by its complex etiology,clinical manifestations,and diagnostic challenges.This study examines the clinical pathology immunohistochemistry,and ultrastructural features of skin biopsies from three patients with Lafora disease within a single family.Methods:Clinical data,skin biopsy pathology,ultrastructural pathology,and genetic changes of three Lafora disease patients diagnosed at Guangzhou KingMed Laboratory Center in March 2022 were collected.The 3 patients,all from the same family,included 1 male and 2 females,and were confirmed by skin biopsy.Biopsies were taken from the right axillary skin of each patient and processed for standard procedures:fixation in neutral formalin,Hematoxylin and Eosin(HE)staining,periodic acid-Schiff(PAS)staining,amylase digestion-periodic acid-Schiff(D-PAS)staining,periodic acid-Schiff and alcian blue(AB-PAS)staining,and alpha 1-antitrypsin(α1-AAT)immunohistochemical staining.For one patient,additional right axillary skin specimens were fixed in 2.5%glutaraldehyde,Semi-thin sections were stained with toluidine blue to locate sweat glands.The ultrastructure of Ultrathin section was observed by transmission electron microscope.Results:Light microscopy of skin biopsies from all 3 cases showed only minor changes.HE staining revealed cytoplasmic vacuolation in a few small sweat gland myoepithelial cells,with pale round inclusions identified as Lafora bodies.PAS,D-PAS,and AB-PAS staining were positive for Lafora bodies,while toluidine blue staining was negative,and immunohistochemical staining showed no expression ofα1-AAT in Lafora bodies.Electron microscopy revealed inclusions in the cytoplasm of small sweat gland duct epithelial cells and large sweat gland myoepithelial cells,and nuclear inclusions in the surrounding fibroblasts of small sweat glands.Conclusion:Skin lesions in Lafora disease are subtle,making histological diagnosis challenging.PAS and electron microscopy findings of Lafora bodies provide significant diagnostic value.Comprehensive clinical and family history,combined with clinical examination,pathology,and genetic testing,can aid in early diagnosis.