The only known sequence of tissue changes seen during liver cancer development involves microscopic foci or islands of altered hepatocytes, hepatocyte nodules, a subset of these nodules, the persistent nodules, nodules in nodules and ultimately hepatocellular carcinoma. The nodules show an array of architectural, fine ultrastructural, vascular, biochemical and physiological properties characteristic of this new population of hepatocytes. Despite their origin following initiation with a chemical carcinogen, the vast majority (98-99%) of nodules undergo a complex process of remodeling or redifferentiation to normal looking mature liver. A very small minority persist, continue to grow slowly and ultimately may act as a site of origin for new later precancerous nodules and metastasizing hepatocellular carcinoma. The basis for the different behaviour patterns, remodelling of the majority and persistence of the minority is not understood. Even though the vast majority of nodules do undergo remodelling and “disappear”, it would be unwise at this time to ignore this key role of nodules in general in cancer development.
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