Hepatic stellate cell activation in dysplastic nodules: evidence for an alternate hypothesis concerning human hepatocarcinogenesis

We have previously suggested that dysplastic nodules (also referred to as "adenomatous hyperplasia" or "macroregenerative nodules"), likely precursors of hepatocellular carcinoma (HCC), develop as an infiltrating clonal expansion, in advance of or parallel to cirrhosis. As part of this hypothesis, to explain aspects of their gross and microscopic appearance, we suggested that dysplastic nodules are resistant to the scarring process affecting the rest of the liver. We sought to test this hypothesis by examining the distribution of activated hepatic stellate cells (HSCs), the hallmark of hepatic scarring, in cirrhotic nodules, dysplastic nodules and HCC. We immunohistochemically stained 56 cirrhotic nodules, 20 low grade dysplastic nodules, 27 high grade dysplastic nodules, and 20 HCCs with monoclonal antibodies against alpha-smooth muscle actin to identify activated HSCs. Distribution and number of HSCs were graded semiquantitatively (0 to 4+). In our results, HSCs were significantly less widespread in dysplastic nodules than in cirrhotic nodules or in HCCs (both: p < 0.00001). HSCs were also more prominent in the periphery of dysplastic nodules than in the center, though still fewer in number than in cirrhotic nodules. In conclusion, the low number of activated HSCs in dysplastic nodules, compared to both cirrhotic nodules and HCC, supports our hypothesis concerning dysplastic nodule development: that they arise as clonal expansions of neoplastic hepatocytes in advance of, or parallel to, the development of cirrhosis.     

THe cost of radiotherapy. Piedmontese experience]

The blood supply of hepatocellular carcinoma (HCC) is primarily arterial. Recent studies reported differences of vascular, especially arterial, supply among low- and high-grade dysplastic nodules and HCC. We assessed arterialization using monoclonal antibody specific for smooth muscle actin as well as simultaneous changes in sinusoidal capillarization in cirrhotic nodules, dysplastic nodules, and HCC. We immunohistochemically stained 56 cirrhotic nodules, 20 low-grade dysplastic nodules, 27 high-grade dysplastic nodules, and 20 HCCs for alpha smooth muscle actin (to identify unpaired arteries (i.e., arteries not accompanied by bile ducts) and CD34 (indicating sinusoidal capillarization). Distribution and number of unpaired arteries and distribution of sinusoidal capillarization were graded semiquantitatively. Unpaired arteries were rare in cirrhotic nodules, significantly more common in dysplastic nodules of both types (p < 0.00001), and most common in HCC. Sinusoidal capillarization was least common in cirrhotic nodules, significantly more common in dysplastic nodules (p < 0.0035), and most common in HCC. No topographic relationship between unpaired arteries and sinusoidal capillarization was identified. These findings showed that (1) distributions of sinusoidal capillarization and unpaired arteries in dysplastic nodules are intermediate between those in cirrhotic nodules and HCC, supporting dysplastic nodules as premalignant lesions; (2) unpaired arteries are histologically useful for distinguishing dysplastic nodules from large cirrhotic nodules; and (3) areas of sinusoidal capillarization within dysplastic nodules are unrelated to location of arterialization.     

Immunohistochemical localization of metallothionein in hepatocellular carcinoma: preferential expression in non-cancerous cirrhotic nodules

Metallothionein (MT), an oncofocal gene product was strongly expressed in 35%-95% of hepatocytes in hepatocellular carcinoma (HCC) and MT-positive hepatocytes were localized mainly in the non-cancerous cirrhotic nodules but not in malignant hepatocytes. On the other hand, <10% hepatocytes showed weak staining for MT in chronic hepatitis and cirrhosis of liver. Strong expressions of MT in non-cancerous cirrhotic nodule in HCC and low expressions in liver cirrhosis without HCC indicate a relationship between malignant transformation of hepatocytes and the expression of MT.     

Rates of change in peak expiratory flow and in diurnal variation in peak flow in patients recovering from acute severe asthma

Reexpression of the insulin-like growth factor type II (IGF-II) gene has recently been described in hepatocellular carcinoma (HCC). In this study, we used a nonisotopic in situ hybridization method to analyze the expression of IGF-II mRNA in a series of 28 HCCs arising on cirrhotic and noncirrhotic livers. An immunohistochemical method was used to detect IGF-II peptide. Hepatitis B virus (HBV) status and the histological differentiation degree were also evaluated. Increased expression of IGF-II mRNA was found in 4 of 28 HCCs, and 7 of 17 cirrhotic patients showed IGF-II mRNA in the cirrhotic nodules surrounding the HCC. A slightly higher rate of positivity for IGF-II mRNA was found in the HBV-negative patients than in HBV-positive ones. Positive immunostaining for the IGF-II peptide in the HCC and/or in surrounding cirrhotic nodules was found in 10 of 28 cases. The normal hepatocytes of the noncirrhotic patients were always negative for IGF-II peptide and mRNA. The similarities between our results and those from experimental models in woodchucks seem to support the concept that heterogeneous phenotypic groups could exist in human HCCs.     

Liver cell dysplasia in liver cirrhosis and hepatocellular carcinoma

The aim of the study was to assess the incidence of both types of liver cell dysplasia and concomitance with cirrhosis, hepatocellular carcinoma (HCC) and positive reaction for HBsAg in the autopsy material and an attempt to determine a relationship between these two types of liver cell dysplasia and hepatocellular carcinoma. Autopsy material included 102 cases of hepatocellular carcinoma, 101 cases of hepatocirrhosis without accompanying cancer and 106 control cases. Histological specimens stained with HE were analyzed for the presence of large liver cell dysplasia (LLCD) according to Anthony et al., small liver cell dysplasia (SLCD) according to Watanabe et al., the presence of macroregenerative nodules (< 8 mm) and antigen HBs (stained with orcein according to Shikata). The detected LLCD were also assessed semiquantitatively taking into account the number of dysplastic areas in a given case. Statistical significance of the results was tested with the chi square test. LLCD was most frequently detected in HCC with concomitant cirrhosis (55.3%), then in cirrhosis without HCC (40.6%), and in HCC without cirrhosis only in 12.5%. LLCD was found significantly more frequently (p < 0.05) in cirrhosis with HCC than in cirrhosis without HCC. Antigen HBs was found in 25.6% of cirrhoses and/or HCC. No significant differences in the presence of HBsAg were seen between the analyzed groups. The incidence of LLCD and HBsAg in controls was significantly lower than in other groups. A mean age at death in case of cirrhosis with HCC subdivided into that with or without LLCD was not significantly different, whereas in case with cirrhosis with LLCD age at death was 10.8 years higher (the difference statistically significant). Analysis of material with respect to gender revealed a high proportion of men in case of HCC with concomitant cirrhosis but without LLCD (13:1). A strong relationship was seen between the presence of positive reaction for HBsAg and LLCD (p < 0.001). Also the intensity of LLCD positively correlated with the presence of HBsAg. Furthermore, a positive correlation was seen between the presence of LLCD and macronodular cirrhosis (posthepatitic). The present findings suggest a closer relation between HBV infection and LLCD than between cirrhosis or HCC and LLCD. Also morphological patterns of LLCD foci do not confirm the hypothesis of some investigators about the precancerous character of these lesions. In the whole current material only seven cases of SLCD were detected. They were all present in cirrhotic livers with concomitant HCC. Both the morphological pattern of these lesions and their sometimes discerned close spatial relation with HCC foci indicate that SLCD is an alternative way of HCC development.     

Blood flow rate: an important determinant of urea clearance and delivered Kt/V

PURPOSE: To compare the magnetic resonance (MR) imaging findings of primary hepatocellular carcinoma (HCC) in cirrhotic versus noncirrhotic livers. MATERIALS AND METHODS: MR images in 36 patients with HCC (30 men and she women aged 42-84 years [mean age, 65 years]) were retrospectively reviewed. The number and size of hepatic lesions were assessed. Lesion margins were categorized as well circumscribed or ill defined. The presence of a capsule, intratumoral high signal intensity on T1-weighted MR images, and a stellate scar were determined. RESULTS: Eleven (31%) patients had MR imaging evidence of cirrhosis, and 25 (69%) did not: Lesions in cirrhotic livers differed significantly from those in noncirrhotic livers in terms of size (22 cm2 vs 99 cm2, P < .05), frequency of a solitary lesion (27% vs 72%, P < .05), and frequency of a central scar (6% vs 50%, P < .05). There was no difference between the cirrhotic and noncirrhotic livers with regard to tumor margin, intratumoral high signal intensity on T1-weighted images, or tumor capsule. CONCLUSION: Differences exist in the MR imaging appearance of HCC between patients with and those without cirrhosis, although there is overlap of imaging findings.     

Hepatocellular carcinoma in an orthotopic mouse model metastasizes intrahepatically in cirrhotic but not in normal liver

Prognosis of hepatocellular carcinoma (HCC) still remains poor mainly because of intrahepatic metastasis. In the majority of cases, HCC is found in conjunction with liver cirrhosis. It is, therefore, of great importance to investigate the invasive and metastatic behavior of HCC in cirrhotic liver. To examine this, a liver cirrhosis model was produced by injecting thioacetamide i.p. into mice. Murine HCC cells were labeled with the fluorescent carbocyanine dye, DiI, and implanted directly under the capsule of cirrhotic and normal livers of syngeneic mice. DiI-labeled HCC cells in the liver were observed under fluorescent and confocal microscopy. Histological analysis of cirrhotic and normal livers revealed that implanted HCC cells migrated to and invaded the adjacent periportal regions, but not the adjacent centrolobular areas. This characteristic behavior of HCC was more evident in cirrhotic liver than in normal liver. Furthermore, intrahepatic metastasis to unimplanted hepatic lobes was observed in cirrhotic liver as early as 7 days after implantation, while it was not detected in normal liver even 4 weeks later. Thus, an orthotopic animal model for HCC with cirrhosis described here may be suitable for investigating the invasive and metastatic behavior of HCC. Importantly, labeling tumor cells with a fluorescent dye before orthotopic implantation may be a convenient and useful method to investigate the invasive and metastatic behavior of various types of cancer.     

Human hepatic preneoplasia: phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia

Foci of altered hepatocytes (FAH) represent preneoplastic lesions, as shown in various animal models of hepatocarcinogenesis, but their significance in the human liver has not been established. The cellular composition, size distribution and proliferation kinetics of FAH in 163 explanted and resected human livers with or without hepatocellular carcinoma (HCC) and their possible association with small-cell change of hepatocytes (SCC) were therefore studied. FAH, including glycogen-storing foci, were found in 84 of 111 cirrhotic livers, demonstrating higher incidences in cases with (29/32) than in those without HCC (55/79). FAH were observed more frequently in HCC-free cirrhosis associated with hepatitis B or C virus or chronic alcoholic abuse (high-risk group) (37/47) than in that due to other causes (low-risk group) (12/21). MCF, predominant in cirrhotic livers of the high-risk group, were more proliferative, larger and more often involved in formation of nodules of altered hepatocytes (39.3%) than were GSF (8.5%). The results suggest that the FAH are preneoplastic lesions, MCF being more advanced than GSF. Oncocytic and amphophilic cell foci were also observed, but their significance remains to be clarified. Two types of SCC, namely diffuse and intrafocal SCC, were identified, but only intrafocal SCC was found to be related to increased proliferative activity and more frequent nodular transformation of the FAH involved, suggesting a close association with progression from FAH to HCC.     

Sinusoidal capillarization of human hepatocellular carcinoma: possible promotion by fibroblast growth factor

Expression of acidic and basic fibroblast growth factors (aFGF and bFGF) and von Willebrand factor (vWF) was immunohistochemically investigated in 55 nodules of human hepatocellular carcinoma (HCC), 15 nodules of adenomatous hyperplasia (AH) of the liver and 10 cirrhotic livers (LC). AH, a putative preneoplastic lesion in the cirrhotic liver, was subdivided into ordinary and atypical types: the former was characterized by little cellular and structural atypia and the latter had some atypia equivocal as to benignity and malignancy. The positive rates of FGF (aFGF and/or bFGF) were as follows: 0% in LC, 20% in AH (ordinary and atypical) and 42% in HCC, whereas the positivity of vWF was 10% in LC, 20% in ordinary AH, 30% in atypical AH and 40% in HCC. There was no correlation between the expression of FGF or vWF and the size of HCC. No correlation was also found between the positivity of FGF and that of vWF in HCC and atypical AH. While vWF was not constantly expressed in the vicinity of FGF-positive HCC cells, capillarized sinusoids were significantly more numerous in FGF-positive cases than in FGF-negative cases (p < 0.01). These data indicate that FGF may be pathogenetically linked to the multistep development of HCC in relation to sinusoidal capillarization.     

Tenascin and type IV collagen expression in liver cell dysplasia and in hepatocellular carcinoma

The extracellular matrix (ECM) located in and around tumors is different from normal organ stroma, and there is evidence that it is critically involved in carcinogenesis and malignant growth. Whereas an abnormal composition of ECM in hepatocellular carcinomas (HCC's) has previously been demonstrated, not much is known so far with respect to putative HCC precursor lesions. We have, therefore, systematically analyzed the immunohistochemical reactivity for two major ECM components, tenascin and type IV collagen, in three types of liver cell dysplasia (LCD), and compared the findings with patterns observed in HCC's of different types and grades. Tenascin reactivity was generally stronger in HCC's than in cirrhosis. In cirrhotic nodules harboring areas of LCD, tenascin expression was significantly lower in small cell LCD than in large cell LCD. Type IV collagen reactivity in and around HCC's decreased as a function of a lower differentiation grade. In both groups of cirrhosis, i.e. with or without HCC, cirrhotic nodules occupied by the small cell variant of LCD exhibited a significantly lower type IV collagen reactivity than those with large cell LCD or simple regenerative cells. Taken together these findings suggest that, similar to adenomatous hyperplasia, small cell LCD is characterized by an abnormal tenascin and type IV collagen expression, thus reflecting the defective ECM pattern observed in HCC's.     

Percutaneous ethanol injection in the treatment of hepatocellular carcinoma. A multicenter survey of evaluation practices and complication rates

BACKGROUND: Percutaneous ethanol injection (PEI) has become a widely used procedure in the treatment of hepatocellular carcinoma (HCC). However, the criteria for selecting patients are not standardized, and little information is available about the complications of the procedure. METHODS: A questionnaire was sent to 11 experienced Italian centers. It investigated: the size and the number of HCC nodules suitable for treatment and the Child-Pugh risk class of the associated cirrhosis; the performance of the procedure; the number and characteristics of the patients treated; and, finally, any complications. RESULTS: Most of the centers performed PEI in single HCC nodules less than 5 cm in diameter or in multiple nodules if fewer than three, the larger being less than 3 cm. Patients in Child-Pugh's classes A, B, and C with single nodules were generally considered for PEI. A prothrombin time of less than 40% and a platelet count of less than 40,000/mm3 contraindicated PEI in most of the centers. PEI was generally performed on outpatients, using Chiba or spinal needles. One thousand and sixty-six patients (8118 sessions) were enrolled; 74% had a single HCC nodule and 26% multiple nodules. All except four had cirrhosis; 53% were in Child class A, 38% in class B, and 9% in class C. The mean number of sessions needed to destroy an HCC nodule was 6.7 (range, 2-14), with a mean alcohol injection volume of 5.0 ml per session (range, 2-20 ml). One death (0.09%) and 34 complications (3.2%) were reported. Among the complications we call attention to the hemorrhagic ones (eight cases) and tumoral seeding (seven cases). Severe pain experienced during the maneuver led to discontinuation of the procedure in 3.7% of the patients; 13.5% of the patients required analgesics and 24% had fever after PEI. CONCLUSIONS: Some procedural aspects of PEI treatment differ among the various centers a standardization is advisable. In the present survey PEI is a low-risk technique.     

Laparoscopic prediction of hepatocellular carcinoma in cirrhosis patients

Previously, laparoscopic studies have not been successful in predicting the occurrence of small hepatocellular carcinoma because cirrhotic patients had not been separated into groups of those who developed small hepatocellular carcinoma under 3 cm in diameter, and those who did not. Retrospective examination with better separation of the two groups gave improved results. Of the 26 laparoscopic findings, only the presence of large complex regenerative nodules was closely associated with the occurrence of subclinical small hepatocellular carcinoma. The study of other cirrhotic patients with and without large complex regenerative nodules gave a cumulative hepatocellular carcinoma occurrence rate of 73% for patients who had these nodules by the third year after laparoscopy. In contrast, the rate for patients without such nodules was 6%, showing a significant difference (P < 0.05) between the two groups. We concluded that the laparoscopic finding of large complex regenerative nodules of liver cirrhosis can be used to predict the occurrence, or a complication, of subclinical small hepatocellular carcinoma.     

The first 300 videothorascopic (VTS) and video-assisted (VATS) operations

To diagnose hepatocellular carcinoma (HCC) functionally and immediately, we examined the usefulness of indocyanine green (ICG) injection during ultrasound-guided liver biopsy. Liver specimens were obtained after intravenous ICG injection by ultrasound-guided biopsy from 251 space-occupying lesions (SOL) in 136 patients. The tissues were immediately examined for ICG uptake using an infrared Vidicon camera and were also subjected to histopathological examinations. Of the 112 ICG-negative biopsy specimens, 105 were histologically diagnosed as HCC, 6 as dysplastic nodules (DN) and 1 as a regenerative nodule (RN). Of the 139 ICG-positive specimens, 18 were diagnosed as HCC, 1 as DN and 120 as RN. The sensitivity of the absence of ICG uptake (SEAIU), the specificity of the absence of ICG uptake (SPAIU), and the positive predictive value of the absence of ICG uptake (PPAIU) for the diagnosis of HCC were 85.3%, 94.5% and 93.8%, respectively. Of the 251 SOLs, 184 were less than 2 cm. SEAIU, SPAIU and PPAIU for the diagnosis of these small HCC were 85.3%, 94.5% and 91.4%, respectively. These results support the reliability of ICG injection during ultrasound-guided liver biopsy to diagnose even small HCC.     

Hepatitis, cirrhosis, and hepatoma

Virus hepatitis and liver cirrhosis are found at high incidence in Asia, and they require not only biochemical examination of blood but also subsequent imaging, because they are often complicated by hepatocellular carcinoma (HCC). It is, therefore, very important to know the specific appearances of hepatitis, liver cirrhosis, and HCC when we diagnose these diffuse liver diseases. Liver necrosis due to severe hepatitis is seen as high intensity on T2-weighted spin echo images. Regeneration is seen as low intensity on T2-weighted images. Morphologic and pathologic changes of cirrhotic liver are well demonstrated by MR imaging techniques. Fibrotic septum with inflammatory cell infiltration or rich pseudo bile duct show high intensity on T2-weighted images, and regenerating nodules shows low intensity. Gradient echo images show regenerating nodules with iron deposition as low-intensity nodules due to susceptibility artifact. MRI also has the potential to evaluate function of diffuse liver disease, cirrhosis, and hepatitis. MRI can visualize and diagnose HCC objectively. Dynamic MRI is very useful for diagnosing HCC. It is also applied for evaluation of effect after transcatheter arterial chemoembolization, because it shows enhancement only in the viable region at an arterial phase. MRI is less invasive and is thus an extremely important form of liver imaging.     

Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: matched case-control study, pathological analysis, and pathogenetic hypothesis

Large cell change (LCC), characterized by cellular enlargement, nuclear pleomorphism and hyperchromasia, and multinucleation of hepatocytes, is a common lesion in cirrhotic livers, but its nature, significance, and pathogenesis remain uncertain. Therefore, we assessed the prognostic value of LCC as a marker of subsequent hepatocellular carcinoma (HCC) through a case-control study that compared pretransplant liver biopsy specimens from 37 cirrhotic liver transplant recipients with HCC to specimens from a control group of recipients without HCC, matched for sex, age (+/-5 years), and cause of cirrhosis. LCC was identified in 16 (43%) of the study and 7 (19%) of the control group biopsy specimens. By matched-pair analysis, LCC conveyed a moderately increased risk of later HCC with an estimated odds ratio of 3.3 (95% CI, 1.2-15; P = .038). However, a pathology review of 45 HCCs showed adjoining LCC in only 12 (27%) and did not suggest a morphological transition or a histogenetic association between the two lesions. LCC hepatocytes displayed a low proliferative rate by Ki-67 or proliferating cell nuclear antigen immunostaining (labeling indices of 0.27 and 0.73) but showed a greater degree of apoptosis than normal hepatocytes (labeling indices of 1.9 and 0.23; P = .03) To reconcile these findings, we propose that LCC derives from derangements in the hepatocyte's normal process of polyploidization. Such derangements, possibly caused by chronic inflammation-induced DNA damage, could yield a population of enlarged liver cells with nuclear atypia and pleomorphism, frequent binuclearity, and minimal proliferation. According to this hypothesis, LCC would be a habitual feature of cirrhosis and a regular accompaniment of HCC but would not represent a direct malignant precursor.     

Serial changes in serum alpha-fetoprotein prior to detection of hepatocellular carcinoma in liver cirrhosis

In 49 liver cirrhosis patients with hepatocellular carcinoma in which the hepatocellular carcinoma nodule was smaller than 30 mm in size, serial changes in serum alpha-fetoprotein levels prior to the detection of the hepatocellular carcinoma were studied retrospectively, and compared with those of 70 cirrhotic patients with no hepatocellular carcinoma. The changes in alpha-fetoprotein levels were classified into the 4 types normal, low plateau, high plateau and spiky type. The spiky type (spiky elevation during a short period) was more frequently noted in the patients with hepatocellular carcinoma than in those with liver cirrhosis. In a prospective analysis of 39 patients with liver cirrhosis, hepatocellular carcinoma was detected in 6, and was also more frequently noted in the spiky type than the other types. Moreover, in the hepatocellular carcinoma patients with the spiky type of alpha-fetoprotein, hepatocellular carcinoma was suspected, on the basis of the tumor doubling time, to exist at the time of the first elevation of alpha-fetoprotein. These results suggest that the liver cirrhotics with the spiky type of alpha-fetoprotein may be considered to be a high-risk group of hepatocellular carcinoma.     

Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men. Genetic and pharmacological evidence

Inhibin is a heterodimeric glycoprotein originally detected in gonadal tissues. One report described inhibin immunopositivity in 17 of 19 hepatocellular carcinomas (HCCs) and the hepatocytes of the surrounding nonneoplastic parenchyma. The reported immunohistochemical method, which used avidin-biotin complex, did not describe blocking endogenous biotin. Since liver tissue may contain high levels of biotin, endogenous biotin may result in false-positive immunostaining. We wondered whether this reported immunopositivity represented a false-positive result due to unblocked endogenous biotin. By using a similar antigen retrieval technique and the same specificity, titer, and clonal source of primary antibody as the aforementioned study, we performed immunostaining for inhibin with and without an endogenous biotin blocking step on 23 cases of HCC and the surrounding cirrhotic liver. In all cases, the HCC and the hepatocytes in the cirrhotic nodules were negative for inhibin when the endogenous biotin blocking step was used. When the blocking step was omitted, apparent immunostaining was noted in 20 of 23 HCCs and in the hepatocytes in all cases. Accordingly, HCC and the hepatocytes of the surrounding cirrhotic liver are immunohistochemically negative for inhibin. The previously reported immunopositivity of HCC and nontumoral hepatocytes for inhibin represents a false-positive result due to endogenous biotin.     

Child, adolescent and general psychiatry

The incidence and characteristics of hepatic tumors -primitive or secondary- were analyzed in a series of 596 patients with cirrhosis and on whom an autopsy was carried out. A hepatic tumor was discovered in 43.6%: 96.5% with histological findings of malignant disease and only 3.4% with benign disease. The tumors discovered showed the following in order of frequency: hepatocellular carcinoma (90.3%), hepatic metastases (4.2%), cholangiocarcinoma (2.3%), adenoma (1.5%), hemangioma (1.2%) and hamartoma (0.8%). Therefore, 10% of the neoplasms located in the cirrhotic liver were different from the hepatocellular carcinoma. In 2% of the subjects with hepatic tumors, two histologically different lesions were found to co-exist in the liver, and in every case it was found to be a hepatocellular carcinoma related to another tumor, which further complicated the diagnosis. The most frequent type of hepatocellular carcinoma was multinodular, although diffuse tumors most frequently developed metastases. When the hepatocellular carcinoma was uninodular and small, distal spread was exceptional. Metastatic infiltration of the liver by neoplasms of different origin, characteristically infrequent in cirrhosis, was always accompanied by spread to other organs and did not appear as a single nodule in any case. We conclude that the correct diagnosis of tumor-related lesions located, in a cirrhotic liver is occasionally difficult during life, especially when the neoplasms are different from the hepatocellular carcinoma.     

An unusual hyperplastic hepatocellular nodule in a patient with hepatitis C virus-related liver cirrhosis

Recent advances in diagnostic imaging techniques have increased the likelihood of detecting novel nodular lesions of the liver. We report here a case of unusual hyperplastic hepatocellular tumor found in a 70-yr-old woman with hepatitis C virus-related cirrhosis. A mass was incidentally detected in the right lobe by abdominal ultrasonography and confirmed by computed axial tomography (CT). Magnetic resonance imaging demonstrated that the tumor had hyperintense signal with a small hypointense region in the center and a thin, hypointense rim on T1-weighted image and a hypointense signal on T2-weighted image. CT during hepatic arteriography showed that the tumor was hypodense with a central hyperdense region, whereas CT during arterial portography revealed that the tumor was isodense and surrounded by a thin circular hypodense band with a central hypodense region. These radiographic findings suggested a diagnosis of dysplastic nodule with malignant foci of hepatocellular carcinoma. The patient underwent tumor resection. Macroscopically, the tumor, 45 x 45 x 30 mm in size, was encapsulated and had a central stellate-like scar with radiating septa. Histological examination showed a hyperplastic hepatocellular tumor without cellular, nuclear or structural atypia. The central fibrous scar contained abundant small, artery-like and vein-like vessels, whereas there were no normal portal triads but rather several portal tract-like structures lacking bile ducts in the parenchyma of the tumor. Some of the portal tract-like structures were composed of artery-like and vein-like vessels, and the others possessed vein-like vessels only. There were no bile ducts in the tumor. The nontumorous liver tissue had evidence of macronodular cirrhosis. Finally, this tumor was regarded as an unusual type of hyperplastic hepatocellular nodule encountered in cirrhotic liver, characterized by the presence of central stellate-like fibrosis and the lack of bile ducts. Although the pathogenesis of the hyperplastic lesion is unclear, it may represent a focal regenerative hepatocellular response to localized circulatory disorder.