Origin of neovascular structure in an early stage of hepatocellular carcinoma: study of alpha-smooth muscle actin immunohistochemistry in serial thin sections of surgically resected cancer.

Background: To elucidate the origin of the neovascular structure found in well-differentiated hepatocellular carcinoma (HCC), an immunohistochemical study was performed on sequential thin section specimens.

Method: Eleven surgically resected specimens of well-differentiated HCC were analyzed for neovascular structure using monoclonal alpha-smooth muscle actin (alpha-SMA) antibody. Each paraffin specimen was serially sliced to a thickness of 3 microm for immunohistochemistry. When a ring-shaped structure was found unrelated to portal triads on alpha-SMA staining, it was regarded as abnormal neovascularity (non-triadal vessel or unaccompanied vessel).

Results: All of the 11 liver cancers had thin-walled, round- or oval-shaped non-triadal vessels in their well-differentiated parts. Immunohistochemistry of serial thin sections of HCC showed that these non-triadal vessels were connected to portal veins in portal triads in well-differentiated cancer in a total of nine patients (81.8%). This type of neovascular structure found in a well-differentiated cancer seemed to be a surviving portal vein among diminishing and disappearing arteries and bile ducts. All 11 tumors showed isovascular staining on ordinary digital subtraction angiography, and four of the tumors showed negative enhancement on intra-arterial carbon dioxide-enhanced ultrasonography or computerized tomographic (CT) hepatic arteriography, suggesting a relative arterial blood scarcity in the tumor nodules.

Conclusion: At an early stage of HCC, non-triadal vessels originate from ordinary portal veins in intratumoral portal triads. This fact sufficiently explains the reason why a well-differentiated liver cancer can sometimes show arterial blood paucity on CT arteriography or enhanced ultrasonography.