O'Shea Anne-Marie, Wilson Gregory J, Ling Simon C, Minassian Berge A, Turnbull Julie, Cutz Ernest
Department of Pathology and Laboratory Medicine, The Mount Sinai Hospital, Toronto, Ontario, Canada.
Pediatr Dev Pathol. 2007 Sep-Oct;10(5):351-7. doi: 10.2350/06-12-01948.1.
We report 2 cases of ground-glass hepatocyte inclusions occurring in pediatric patients. Case 1 had alpha-thalassaemia major and was receiving iron chelation therapy, whereas case 2 had trisomy 21 with a history of bone marrow transplantation for acute myeloid leukemia. The liver sections in both cases showed eosinophilic, periodic acid-Schiff diastase-positive intracytoplasmic inclusions that were negative for hepatitis B surface antigen. Immunohistochemically the inclusions showed positive staining with KM279, a monoclonal antibody against polyglucosan derived from Lafora inclusions. On electron microscopy, in case 1, intracytoplasmic inclusions were composed of degenerate organelles, glycogen, and irregular fibrillar structures; in case 2, they were composed of vesicular structures containing granular material. Ultrastructural changes in both cases differed from classical Lafora inclusions and ruled out hepatitis B surface antigen, glycogenosis type IV, and fibrinogen storage disease. Genetic analysis of the Lafora's disease genes performed in case 2 revealed no mutations. The development of hepatocyte cytoplasmic inclusions in both our cases could be related to medication effects, because similar inclusions were reported in patients using cyanamide. Drug-induced inclusions, mimicking Lafora's disease, should be included in the differential diagnosis of hepatocyte ground-glass inclusions.
我们报告了2例发生在儿科患者中的毛玻璃样肝细胞包涵体病例。病例1患有重型α地中海贫血,正在接受铁螯合治疗,而病例2患有21三体综合征,有因急性髓系白血病进行骨髓移植的病史。两例患者的肝脏切片均显示嗜酸性、过碘酸-希夫淀粉酶阳性的胞质内包涵体,乙肝表面抗原检测为阴性。免疫组化显示,这些包涵体用KM279呈阳性染色,KM279是一种针对源自拉福拉包涵体的聚葡萄糖的单克隆抗体。电子显微镜检查显示,病例1的胞质内包涵体由退化的细胞器、糖原和不规则的纤维状结构组成;病例2的包涵体由含有颗粒物质的囊泡结构组成。两例患者的超微结构变化均不同于典型的拉福拉包涵体,排除了乙肝表面抗原、IV型糖原贮积病和纤维蛋白原贮积病。对病例2进行的拉福拉病基因的遗传分析未发现突变。我们这两例患者肝细胞胞质包涵体的形成可能与药物作用有关,因为在使用氰胺的患者中也报告了类似的包涵体。模仿拉福拉病的药物性包涵体应纳入肝细胞毛玻璃样包涵体的鉴别诊断。