Turlin B, Deugnier Y
Department of Pathology, Pontchaillou University Hospital, Rennes, France.
Semin Diagn Pathol. 1998 Nov;15(4):237-45.
Faced with hepatic siderosis, the pathologist must (1) determine the parenchymal, mesenchymal, or mixed type of iron overload; (2) quantify liver iron by either histology or biochemistry; (3) seek for associated iron-related lesions, especially sideronecrosis, fibrosis, and iron-free-foci; and (4) assess any other liver damage. The discovery of the HFE gene has modified the management of hemochromatosis. Because homozygosity for the C282Y mutation is diagnostic of the condition regardless of the liver iron concentration-to-age ratio, indication for liver biopsy in C282Y homozygotes is restricted to the assessment of prognostic lesions, such as fibrosis and iron-free-foci. In patients with a phenotype compatible with hemochromatosis but nonhomozygous for the C282Y mutation, liver biopsy remains mandatory to assess nonhemochromatosis causes of iron overload (rare hereditary defects of iron metabolism and transport and iron overload secondary to polymetabolic syndrome, to porphyria cutanea tarda, or to cirrhosis). The evaluation of iron distribution within liver cells and throughout lobules and the assessment of associated lesions are the most important features that allow for correct classification of nonhemochromatosis iron-overload syndromes.
面对肝铁沉积症，病理学家必须：（1）确定实质型、间质型或混合型铁过载；（2）通过组织学或生物化学方法对肝脏铁进行定量；（3）寻找相关的铁相关病变，特别是铁坏死、纤维化和无铁灶；（4）评估任何其他肝脏损伤。HFE基因的发现改变了血色素沉着症的管理。由于C282Y突变的纯合性可诊断该病，而无需考虑肝脏铁浓度与年龄的比值，因此C282Y纯合子患者进行肝活检的指征仅限于评估预后性病变，如纤维化和无铁灶。对于表型与血色素沉着症相符但C282Y突变非纯合子的患者，仍需进行肝活检以评估铁过载的非血色素沉着症病因（罕见的铁代谢和转运遗传缺陷以及继发于多代谢综合征、迟发性皮肤卟啉症或肝硬化的铁过载）。评估肝细胞内及整个肝小叶内的铁分布以及相关病变是正确分类非血色素沉着症铁过载综合征的最重要特征。
