Image shows:Hereditary hemochromatosis. In this Prussian blue– stained histologic section, hepatocellular iron appears blue. The parenchymal architecture is normal.
- Hereditary hemochromatosis refers to genetic disorders characterized by excessive accumulation of body iron, most of which is deposited in the liver, pancreas, and heart.
- The hereditary hemochromatosis gene, responsible for the most common form of this disorder, is called HFE. It is located on the short arm of chromosome 6.
- Acquired forms of iron accumulation from known sources of excess iron are called secondary iron overload. Among the most important are multiple transfusions, ineffective erythropoiesis (as in β-thalassemia and myelodysplastic syndromes), and increased iron intake.
- Fully developed cases show (1) cirrhosis (seen in all patients), (2) diabetes mellitus (in 75% to 80% of patients), and (3) skin pigmentation (in 75% to 80%).
- The morphologic changes in hereditary hemochromatosis are all responses to the deposition of hemosiderin in the following organs (in decreasing order of severity): liver, pancreas, myocardium, pituitary, adrenal, thyroid and parathyroid glands, joints, and skin.
- In the liver, iron becomes evident first as golden-yellow hemosiderin granules in the cytoplasm of periportal hepatocytes, which stain blue with the Prussian blue stain.
- With increasing iron load, there is progressive involvement of the rest of the lobule, along with bile duct epithelium and Kupffer cells.
- Iron is a direct hepatotoxin, and inflammation is characteristically absent. At this stage, the liver typically is slightly larger than normal, dense, and chocolate brown.
- Fibrous septa develop slowly, linking portal tracts to each other and leading ultimately to cirrhosis in an intensely pigmented (very dark brown to black) liver