Kenji Doishita

Pathology of the Liver in “Idiopathic Portal Hypertension” Associated with Autoimmune Disease

The histopathology of the liver in idiopathic portal hypertension (IPH) associated with autoimmune disease (15 cases), was examined and compared with that of IPH without autoimmune disease (31 cases). It was found that hepatic histopathology was heterogeneous in the cases with autoimmune disease. That is, the hepatic histopathology in 7 cases was similar to that of classic IPH without autoimmune disease, and the remaining 8 cases disclosed unusual lesions such as focal non suppurative cholangitis, nodular parenchymal hyperplasia, moderate portal inflammation, and intrahepatic ductopenia. These unusual lesions, which frequently coexisted in the same case, were not typical ones for making other diagnoses such as primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. These findings suggest that unusual histologic lesions in the livers of IPH patients with autoimmune disease may represent an accentuated immunologic reaction inherent in IPH, or that such cases may be an abortive or incomplete form of primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. Acta Pathol Jpn 39: 586‐592, 1989.

Intrahepatic cholangiocarcinomas associated with nonbiliary cirrhosis : a clinicopathologic study

To determine the prevalence and clinicopathologic features of cholangiocarcinoma (CC) associated with nonbiliary cirrhosis, we performed a clinicopathologic study. Among the 5,563 autopsies in our laboratories during the past 14 years, 85 (1.5%) were CCs. Four (4.7%) were associated with cirrhosis, due to hepatitis B virus in one case and cryptogenic (probably non-A non-B hepatitis virus) in the remaining three. Clinically, patients with CC and cirrhosis were characterized by male preponderance, lower age, past history of liver injury, and elevated values of zinc sulfate and thymol turbidity tests. Pathologically, all CCs with cirrhosis were basically adenocarcinoma; other histologic features included adenocarcinoma resembling bile ductules without mucin (one case), adenocarcinoma with broad areas of signet ring cell carcinoma (one case), adenocarcinoma with extensive sarcomatoid transformation (one case), and adenocarcinoma associated with hepatoliths (one case). Immunohistochemically, immunophenotypes of carcinoma cells of CC with cirrhosis were not different from those of CC without cirrhosis. Carcinoembryonic antigens, CA19-9, DU-PAN-2, and biliary-type cytokeratins were positive and alpha-fetoprotein was negative, suggesting that our CCs are not hepatocellular neoplasms but true CCs. It must be stressed that there are actual CCs arising in nonbiliary cirrhotic livers.

Quantitation and serial section observations of focal venocclusive lesions of hepatic veins in liver cirrhosis

The pathogenesis and functional significance of the venocclusive (VO) lesions in small hepatic veins occurring in liver cirrhosis, remain controversial. The present study, using quantitative examination and serial sections has disclosed that these lesions are present in 71.7% of 106 autopsy livers with alcoholic, HBsAg-positive, biliary or cryptogenic cirrhosis. The lesions were usually focal: their number in a liver section (10 cm2) was below 15 in 86.7% of the livers having them. The incidence and morphology of the lesions appeared similar in cirrhotic livers with different aetiology. Serial sections disclosed that the affected veins disappeared within the fibrous stroma at one side and were directly connected with the patent larger hepatic veins at other side, indicating that these veins had lost their function as a draining vein of the hepatic parenchyma. In addition, there was frequent recanalization within the VO lesions, and the recanalized vessels frequently communicated with neighboring thin-walled veins in cirrhotic stroma, suggesting an intrahepatic vein to vein anastomosis. In conclusion, VO lesions, when focal, may themselves be responsible to a lesser degree for obstruction of hepatic venous outflow in liver cirrhosis.

Histological study of intrahepatic cavernous transformation in a patient with primary myelofibrosis and portal venous thrombosis

Cavernous transformation in the liver was examined histologically by serial section observations, in an autopsy case of portal venous thrombosis and primary myelofibrosis. Cavernous transformation was present from the hepatic hilus to medium-sized portal tracts and was composed of dilated and thin-walled vessels. Serial sections disclosed that these vascular channels were anastomotic and occasionally communicated with occluded portal venous radicles. In places they entered directly into the hepatic parenchyma without accompanying biliary or arterial elements, and also drained into the patent portal venous branches beyond the occluded segment. The study demonstrated that cavernous transformation in the liver develops as hepatopetal collaterals secondary to the portal venous obstruction. Periportal and peribiliary capillary plexus may become cavernous in the presence of portal venous occlusion.

Intrahepatic bile duct destruction in a patient with sarcoidosis and chronic intrahepatic cholestasis.

An autopsy case of sarcoidosis with chronic intrahepatic cholestasis for 2 and a half years was presented. Generalized distribution of noncaseating epithelioid granulomas and positive Kveim test were consistent with sarcoidosis. Histological examination of the liver revealed extensive bile duct destruction similar to that seen in the liver of primary biliary cirrhosis. Destructive cholangitis found in the liver appeared to be responsible for long term intrahepatic cholestasis, and no sarcoid granulomas in the liver were found to destroy any bile duct. The possible relation in pathogenesis of the bile duct destruction between primary biliary cirrhosis and sarcoidosis was discussed.

Florid duct lesions and extensive bile duct loss of the intrahepatic biliary tree in chronic liver diseases other than primary biliary cirrhosis.

Intrahepatic biliary tree with either florid duct lesions or a moderate to severe degree of the duct loss in four livers with chronic hepatic diseases other than primary biliary cirrhosis were studied with histometric and serial section observations. Florid duct lesions, distributed segmentally in the liver, were found in one case with incomplete septal cirrhosis and one case with idiopathic portal hypertension. The florid duct lesions including marked plasma cell infiltration and occasional periductal granulomas, were not associated with any bile duct loss in the two cases. The duct lesions were reversible in one case during a long clinical course. On the other hand, a moderate to severe bile duct loss with biliary epithelial degeneration and necrosis was associated with no or little periductal inflammatory cell infiltration in one other case with chronic intrahepatic cholestasis, probably drug‐induced, and in one case with idiopathic portal hypertension. Although florid duct lesions and bile duct loss were important diagnostic features of primary biliary cirrhosis, one of them was observed to develop independently in severely diseased livers, not consistent with a diagnosis of primary biliary cirrhosis, sclerosing cholangitis or intrahepatic bile duct paucity syndrome.

A case of hepatic fibrosis with abnormal intrahepatic bile duct

肝内胆管系の異常を伴った肝線維症の1例(53歳,女性)を報告した.アルカリフォスファターゼ値の上昇と高γ-グロブリン血症が7年間持続し,死亡2年前より門脈圧亢進症が出現した.肝組織像では線維化がみられ,特発性門脈圧亢進症の組織豫に一致するものであった.私どもの開発した組織計測法と連続切片法により本例の肝内胆管系を検索したところ,約50～60μ以下の太さの胆管に消失がみられ,胆管消失に付随して胆管上皮の障害がみられた.しかし,原発性胆汁性肝硬変にみられる胆管周囲の浮腫性病変や細胞浸潤はみられなかった.本例と原発性胆汁性肝硬変における胆管崩壊の病態発生に関して,若干の検討を行った.