Focal hyperplastic hepatocellular nodules in hepatic venous outflow obstruction: a clinicopathological study of four patients and 24 nodules

AIMS: In hepatic venous outflow obstruction (Budd-Chiari syndrome), focal hepatocellular nodules are occasionally discovered showing variable morphology. These could be interpreted either as neoplastic (adenoma), regenerative (large regenerative nodule) or reactive to abnormal vasculature (focal nodular hyperplasia). The aim of this study was to investigate their histogenesis and to determine their morphological characteristics in order to provide diagnostic criteria. MATERIAL AND METHODS: Twenty-four hepatocellular nodules were studied, which were found in three explanted livers and in one additional autopsied liver from four patients with Budd-Chiari syndrome. As controls, we employed three explanted livers without nodules from patients who also suffered from Budd-Chiari syndrome. We attempted to classify the nodules morphologically as either adenoma-like, large regenerative nodule or focal nodular hyperplasia-like, using criteria from the literature. RESULTS: Out of the four cases, we observed two nodules in each of two livers, five in the third one and up to 15 in the remaining one. The size of the nodules ranged from 4 to 25 mm. Eleven nodules could be categorized as large regenerative nodules (two of them with a central scar), seven as focal nodular hyperplasia-like and six as adenoma-like. Some large regenerative nodules showed proliferated arteries with muscular hyperplasia similar to that seen in focal nodular hyperplasia. In the individual livers we could find nodules of various categories. Patchy or diffuse monoacinar regeneration was seen in most cases (six out of seven cases) in the macroscopically non-nodular liver parenchyma. In addition, thrombotic obstruction of portal vein branches was present in all except one of the nodular cases, but in none of the controls. Thus, it appears that portal venous obstructions are frequently, but not invariably associated with the development of nodules. CONCLUSIONS: The hepatocellular nodules seen in livers from patients with Budd-Chiari syndrome share morphological characteristics with large regenerative nodules, focal nodular hyperplasia and hepatocellular adenomas. Their multiplicity, the existence of mixed lesions, the frequent hepatocellular regenerative background as well as the frequently associated portal venous obstructions suggest that these nodules are regenerative in nature and conditioned by an uneven blood perfusion throughout the liver. In their differential diagnosis, the clinicopathological context in which they occur is of paramount importance and should allow recognition that those resembling adenomas may not be true neoplasms.