Immunohistochemical demonstration of sinusoidal capillarization in human benign liver tumors: distinction from neoangiogenesis

Abstract To better understand how benign hepatocellular tumors acquire nutrient vessels, we investigated the angioarchitecture of the smallest vessels in hepatocellular adenoma (HA) and focal nodular hyperplasia (FNH). In biopsy or resection specimens, microscopic angioarchitecture was characterized in terms of intratumoral fibrous septa and portal tract. Immunohistochemistry for CD34, factor-VIII-related antigen (F-VIII), type IV collagen (collagen IV), α-smooth muscle actin (α-SMA), and CD68 was performed. HA had no portal tract in fibrous septa although FNH showed portal tract in fibrous septa. The smallest vessels in HA stained diffusely for CD34, and arterial segments of the smallest vessels were stained for F-VIII, and collagen IV. Pericyte surrounding the smallest vessels in HA were stained for α-SMA. The smallest vessels in all but one FNH specimen stained for CD34, F-VIII, collagen IV, and α-SMA along portal tract or the artery. Both HA and FNH stained for CD68, as did normal liver. The results indicate that the smallest vessels in HA and FNH are incomplete capillaries, that have both characters of sinusoid and capillaries morphologically and phenotypically, i.e., capillarized sinusoid as in chronic hepatitis or early well-differentiated hepatocellular carcinoma. Benign hepatocellular tumors such as HA and FNH would acquire new vessels gradually by sinusoidal capillarization, not by rapid arterial angiogenesis.