Denk H, Stumptner C, Fuchsbichler A, Müller T, Farr Gh, Müller W, Terracciano L, Zatloukal K
Department of Pathology, Medical University of Graz, Graz, Austria.
J Pathol. 2006 Apr;208(5):653-61. doi: 10.1002/path.1946.
Mallory bodies (MBs) and intracellular hyaline bodies (IHBs) are cytoplasmic hepatocellular inclusions that consist of aggregated proteins. MBs are characteristically associated with alcoholic and non-alcoholic steatohepatitis, but may also be found in chronic cholestatic and metabolic (eg copper intoxication) diseases and hepatocellular neoplasms, particularly hepatocellular carcinomas. IHBs have hitherto only been described in hepatocellular carcinoma cells. In the present study hepatocellular carcinomas (HCCs) and a case of idiopathic copper toxicosis were evaluated with respect to the presence and mutual relationship of MBs and IHBs. IHBs alone were present in 8.6%, MBs alone in 16.1% and both types of inclusion in 7.5% of HCCs. It is shown that IHBs may also occur in non-neoplastic hepatocytes in association with idiopathic copper toxicosis, together with MBs. In HCCs and idiopathic copper toxicosis, MBs and IHBs may be present within the same cell. Moreover, hybrid inclusions holding an intermediate position between MBs and IHBs regarding light microscopy, ultrastructure and composition exist. MBs and IHBs contain p62, a stress-inducible adapter protein, as the major constituent. In MBs p62 is associated with keratins, whereas classical IHBs lack keratins. Light microscopic, electron microscopic and immunohistochemical data suggest a close pathogenetic relationship between MBs and IHBs. Both types of inclusion are the result of over-expression and accumulation of the stress protein p62. If p62 is induced alone, or at least prevails, IHBs may arise by aggregation. However, if abnormal keratins are present in addition to p62, p62 associates and co-aggregates with keratins, finally leading to classical MBs.
马洛里小体（MBs）和细胞内透明小体（IHBs）是由聚集蛋白构成的细胞质肝细胞内含物。MBs典型地与酒精性和非酒精性脂肪性肝炎相关，但也可见于慢性胆汁淤积性疾病和代谢性疾病（如铜中毒）以及肝细胞肿瘤，尤其是肝细胞癌。迄今，IHBs仅在肝癌细胞中被描述。在本研究中，对肝细胞癌（HCCs）和一例特发性铜中毒病例进行了MBs和IHBs的存在情况及相互关系评估。在HCCs中，单独存在IHBs的占8.6%，单独存在MBs的占16.1%，两种内含物都存在的占7.5%。结果表明，IHBs也可能与特发性铜中毒相关，在非肿瘤性肝细胞中与MBs一起出现。在HCCs和特发性铜中毒中，MBs和IHBs可能存在于同一细胞内。此外，在光学显微镜、超微结构和组成方面介于MBs和IHBs之间的混合性内含物也存在。MBs和IHBs含有应激诱导衔接蛋白p62作为主要成分。在MBs中，p62与角蛋白相关，而典型的IHBs缺乏角蛋白。光学显微镜、电子显微镜和免疫组化数据表明MBs和IHBs之间存在密切的发病机制关系。两种内含物都是应激蛋白p62过度表达和积累的结果。如果单独诱导p62，或至少p62占主导，IHBs可能通过聚集形成。然而，如果除p62外还存在异常角蛋白，p62会与角蛋白结合并共同聚集，最终形成典型的MBs。
