Katsunori Wada

Hepatocellular carcinoma without cirrhosis in Japanese patients

Hepatocellular carcinoma is closely associated with cirrhosis, but it also develops, although much less frequently, in a noncirrhotic liver. It is suspected, without supporting evidence, that hepatocellular carcinoma has a different etiology when associated and not associated with chronic liver disease. In this study, 66 noncirrhotic cases found among 618 autopsies for hepatocellular carcinoma (10.7%) were analyzed retrospectively. The noncirrhotic liver was histologically unremarkable in 3 cases and in the histologically evaluable 56 cases it had fibrosis of varying degrees or mild cellular infiltrate, or both, in the portal tract. There was one liver that had portal venous changes compatible with those in idiopathic portal hypertension (Bantis syndrome). In these noncirrhotic livers, the parenchymal cells were generally unremarkable except for liver cell dysplasia that was seen in 26.8%. Serum hepatitis B surface antigen was positive in only 7.4% in contrast to 26.6% in cirrhotic cases. Three histologically unremarkable cases had no clinical or histologic evidence of chronic liver disease; two involved painter-plasterers and one a farmer. The liver weight in these cases ranged from 4400 to 6180 g. In contrast, the average liver weight in cirrhotic cases was 1998 g. Noncirrhotic patients when compared with cirrhotic patients had better liver function tests and much less frequent varices. It was concluded that approximately 11% of hepatocellular carcinoma cases in Japan are noncirrhotic, the majority having some histologic changes in the portal tracts suggestive of past or ongoing chronic liver disease, and that there are rare cases that have no histologic changes in the liver.

Morphological clues for the diagnosis of small hepatocellular carcinomas

Histological features of 44 cases of small hepatocellular carcinoma (HCC) were examined and compared with those of large regenerative nodules. The highly differentiated type of HCC most often occurred in nodules which were less than 2 cm in diameter. Noticeably, in 9 out of 15 such cases (60.0%), tumour cells were arranged in trabeculae of almost normal thickness (normotrabecular pattern). These trabeculae, however, showed variable nuclear crowding, occasional microacinar formation, and increase in cytoplasmic basophilia. It is emphasized that the presence of this triad may be a very reliable indicator for the histological identification of early HCC, especially in examining limited material such as a biopsy specimen. However, cellular and structural atypia becomes more prominent in nodules which are larger than 2 cm.

Etiological analysis of focal nodular hyperplasia of the liver, with emphasis on similar abnormal vasculatures to nodular regenerative hyperplasia and idiopathic portal hypertension.

Pathological studies were performed on 23 cases of focal nodular hyperplasia (FNH) under the hypothesis that FNH is a hyperplastic lesion caused by abnormal vasculatures of portal tracts within the nodule. For a comparison of the histological features of portal tracts, nodular regenerative hyperplasia (NRH), idiopathic portal hypertension (IPH), chronic hepatitis and so-called normal liver were used as control tissues. Extranodular areas of FNH nodules were also examined. Clinical data were briefly summarized. Most of the portal tracts within FNH nodules showed various abnormal findings, such as dilatation and/or stenosis of portal vein, muscular thickening of arterial wall with dilated or stenotic lumina, lymphocyte infiltration, and bile ductule proliferation. However, portal vein thrombi were not found. These findings were not thought to represent compensatory reaction to portal vein thrombosis. Similar abnormal features were also observed in extranodular areas of FNH although to a milder degree. These abnormal features resembled those of NRH and IPH. Moreover, the characteristic scar-like tissues within FNH nodules were proved to be abnormally large portal tracts including large feeding arteries, portal veins and bile ducts. It has been believed that septa and scar-like tissue within FNH nodules are not portal tracts and that arterial malformation independent of portal tracts are related to the development of FNH. In addition, venous structures within FNH modules have until now not been considered to be portal veins. However, this study revealed that severe anomaly of portal tracts including portal veins and hepatic arterial branches existed in FNH nodules. Moreover, portal tracts in extranodular areas were also abnormal. Clinically, only one patient had a history of oral contraceptives. Based on these findings, congenital anomaly of the portal tracts histologically resembling the abnormal portal tracts of NRH and IPH may be related to the pathogenesis of FNH.

Biliary cystadenocarcinoma of the liver. A clinicopathologic and histochemical evaluation of nine cases

Nine cases of biliary cystadenocarcinoma of the liver were studied, with emphasis on its clinicopathologic features, mucin profiles, and immunohistochemical characteristics. In general, the cystic tumors had protrusions that consisted of well‐differentiated papillary adenocarcinoma cells with or without benign‐appearing epithelial elements. In invading or metastatic foci, the carcinoma cells tended to show distinctive anaplastic changes. Tumor growth was confined to the cystic lesions in five cases (noninvasive type), whereas in four cases it extended to the hepatic parenchyma or neighboring organs (invasive type). There was a considerable difference between the two groups in terms of prognosis. In fact, the patients included in the group with the noninvasive type had no sign of tumor recurrence after an appropriate surgical procedure. With mucin histochemical and immuno‐histochemical approaches, positive reactions with car‐cinoembryonic antigen, tissue polypeptide antigen, carbohydrate 19‐9, and Dupan‐2 and the predominance of sialomucin were observed in most cases of biliary cysta‐denocarcinoma, indicating a similar cellular nature of cholangiocarcinoma. Cancer 1992; 69:2426‐2432.

Interstitial tumour cell invasion in small hepatocellular carcinoma. Evaluation in microscopic and low magnification views.

In order to study the process of hepatocellular carcinoma (HCC) development, and to search for a clue to histologic diagnosis of well‐differentiated HCC (wd‐HCC), interstitial invasion in small HCC was evaluated. The study material consisted of 35 cases of HCC that were smaller than 3 cm that comprised 17 cases of wd‐HCC, 18 cases of moderately or poorly differentiated classical HCC (cl‐HCC), and 20 cases of large regenerative nodules (LRN). Interstitial invasion was microscopically classified into three patterns: (i) crossing type, in which HCC was invading across fibrous septa of tumour nodules; (ii) longitudinal type, in which tumour cells were growing longitudinally within fibrous septa; and (iii) irregular type, in which the portal area was irregularly invaded by HCC. The crossing type was found in two cases (12%) of wd‐HCC and 10 cases (56%) of cl‐HCC while the longitudinal type was observed in 16 cases (94%) of wd‐HCC and eight cases (44%) of cl‐HCC. The irregular type was frequently seen in wd‐HCC (15 cases, 88%), and cl‐HCC (12 cases, 67%). No interstitial invasion was observed in LRN. Interstitial invasion could be recognized even in the low magnification view of histological specimens, with a detection rate of 59% (10 cases) in wd‐HCC and 72% (13 cases) in cl‐HCC.

Morphometric analysis of hepatocellular carcinoma

In order to characterize the cytological features of highly differentiated hepatocellular carcinoma (HCC), a comparative morphometric study was made by observing 30 cases of HCCs and controls (normal, cirrhotic, and atrophic livers). Among trabecular HCCs, normotrabecular subtype (1–2 cell thick cell plate) usually showed minimal cytological atypism and was categorized as well or highly differentiated HCC. Using an image analyzer, the following 4 parameters were applied to quantitate the hepatocyte changes: mean cell size (

Intrahepatic metastasis of hepatocellular carcinoma: A histopathologic study

\bar C

Biopsy diagnosis of well-differentiated hepatocellular carcinoma based on new morphologic criteria

), mean nuclear size (