Scirrhous Hepatocellular Carcinoma Research Articles

Minute scirrhous hepatocellular carcinomas undergoing different carcinogenetic processes

Scirrhous hepatocellular carcinoma (scirrhous HCC) is a rare histological subtype of HCC characterized by marked fibrosis along the sinusoid spaces. Carcinogenetic processes and pathological features at earlier stages of scirrhous HCC remain unclarified. In the present report two cases of minute scirrhous HCC suggesting different carcinogenesis, are described. The first case involved a 54-year-old man with liver cirrhosis related to HCV infection. This patient died of ruptured splenic aneurysm. At autopsy a hepatic tumor measuring 1.8 cm was found, and this tumor had a nodule-in-nodule appearance. Histologically, the inner part of the tumor was well-differentiated HCC with prominent collagen fiber deposition along the sinusoids (scirrhous HCC), whereas the outer part was a high-grade dysplastic nodule. The other patient was a 75-year-old woman who died of hepatic failure due to liver cirrhosis probably related to non-alcoholic steatohepatitis. At autopsy a hepatic tumor (1.2 cm in diameter) was incidentally found in the cirrhotic liver, and was histologically scirrhous HCC without dysplastic nodule elements. Carcinoma cells proliferated along the cirrhotic fibrous septa and replaced regenerative nodules. These two cases suggested that scirrhous HCC could occur in dysplastic nodules (the former case) and also develop de novo in cirrhotic liver (the latter case).

Comparison of CT enhancement patterns and histologic features in hepatocellular carcinoma up to 2 cm: Assessment of malignant potential with claudin-10 immunohistochemistry

The purpose of this study was to compare features of computed tomography (CT) and histologic features of hepatocellular carcinoma (HCC) of up to 2 cm in diameter with the immunohistochemical staining pattern of claudin-10, a recently identified prognostic factor for resected HCC. Twelve cases of resected HCC of up to 2 cm in diameter were assessed retrospectively. Preoperative dynamic CT was reviewed, and three enhancement patterns were identified. Type I (n=6) was defined as a pattern of hyperenhancement throughout the tumor in early-phase CT, decreasing to hypoenhancement in late-phase CT (high-low), a finding characteristic of HCC. Type II tumors (n=2) appeared as an area of hyperenhancement in early-phase CT, and an area of hyperenhancement in late-phase CT (low-high). Histologically, type II tumors were considered unusual types, and included combined hepatocellular-cholangiocarcinoma and scirrhous HCC. In type III tumors (n=4), high-low, low-high and low-low components were observed. Type III tumors showed multinodular-type morphology and comprised both moderately and poorly differentiated HCC with marked necrosis and fibrosis. Each nodule was divided by fibrous septa. In three of the four type III cases, recurrence occurred within 6 months after resection. Immunohistochemistry of claudin-10 showed positivity in five of the 12 cases, including four type III cases. Results of this study suggest that type III tumors have greater malignant potential than the other tumor types.

Contrast-enhanced ultrasonographic spoke-wheel sign in hepatic focal nodular hyperplasia

Background To determine the utility of contrast-enhanced ultrasonography (CEUS) in assessing hepatic tumors with central feeding arteries found by color/power Doppler ultrasonograophy (CDUS/PDUS). Methods We prospectively studied 37 hepatic tumors (34 patients), with a mean size of 2.9 cm and each having a central feeding artery, by CDUS/PDUS. The CEUS was performed with a galactose-based microbubble contrast agent. The detection of a spoke-wheel sign was interpreted as evidence of focal nodular hyperplasia (FNH). All patients underwent tumor biopsies or surgical resection. Results CEUS showed a central feeding artery with a spoke-wheel sign in 36 tumors, including 34 FNHs and 2 hepatocellular carcinomas. The remaining tumor was demonstrated to be FNH despite the absence of a spoke-wheel sign as detected by CEUS. The sensitivity of the spoke-wheel sign or central scar for FNH was 97.1% (34/35), 40% (14/35), 28.6% (10/35), 50% (8/16) and 0% (0/15) for CEUS, CDUS/PDUS, dynamic computed tomography (CT) or magnetic resonance imaging (MRI), hepatic angiography and liver scintigraphy, respectively. The two hepatocellular carcinomas showed scirrhous changes histologically. Conclusions CEUS is more sensitive than CDUS/PDUS, dynamic CT, MRI, hepatic angiography and liver scintigraphy in the detection of the spoke-wheel sign or central scar in FNH. Scirrhous hepatocellular carcinoma should be included in the differential diagnosis for liver tumors with spoke-wheel sign detected by CEUS.

Clinicopathological study of scirrhous hepatocellular carcinoma

Scirrhous hepatocellular carcinoma (SHCC) is characterized by diffuse fibrosis of the tumor, however, its clinicopathological features are not fully clarified. This study aimed to clarify the clinicopathological features of SHCC. Among 546 consecutively resected HCC without preoperative anticancer therapies, 25 SHCC were selected for the study and compared with 521 cases without scirrhous as the control. SHCC accounted for 4.6% of cases. On diagnostic imagings, SHCC was frequently misdiagnosed as cholangiocarcinoma (CC), combined HCC-CC or metastatic carcinoma. Overall survival rate was significantly higher than the control. The average (+/-SD) tumor size of SHCC was 3.4 +/- 1.8 cm without significant difference to the control. The majority of SHCC (88%) were located close to the liver capsule. SHCC was characterized by stellate fibrosis (84%), no encapsulation (100%), no necrosis and hemorrhage (100%), intratumoral portal tracts (80%), remarkable lymphocyte infiltration (84%), clear cell change (84%), and hyaline bodies (52%). The number of alpha-smooth muscle actin-positive myofibroblast-like cells (activated stellate cells) in the tumor was about three times more than that in the control. Regarding the developmental mechanism of scirrhous change, a close correlation with unique tumor location and activation of stellate cells was suggested. SHCC presents with characteristic clinicopathological features and the recognition of SHCC is important for both clinicians and pathologists.

Cellular and stromal characteristics in the scirrhous hepatocellular carcinoma: Comparison with hepatocellular carcinomas and intrahepatic cholangiocarcinomas

Scirrhous hepatocellular carcinoma (SHCC) is a rare variation of HCC, for which characteristics of tumor cells and the fibrotic stroma have not been clarified in detail. The present study was therefore carried out to elucidate cytological features of tumor and stromal cells and components of the stromal extracellular matrix in 15 SHCC patients undergoing hepatectomy without preoperative transarterial embolization. Diagnosis was on the basis of a scirrhous histological pattern exceeding 50% of the tumor area. Expression of cytoplasmic and extracellular matrix proteins was compared among SHCC, HCC and intrahepatic cholangiocarcinoma (ICC) cases with immunohistochemical staining. The lesions could be histologically divided into radiating and sinusoidal types. Common stromal components of SHCC and ICC were collagen types I and III. There was no expression of laminin-5 in the stroma of SHCC, but it was present in almost all ICC cases. Tenascin-C expression was significantly lower in the SHCC cases and its distribution differed between SHCC and ICC. Matrix metalloproteinase-7 (MMP-7) expression was significantly higher in SHCC compared with HCC. Almost all stromal cells were alpha-smooth muscle actin-positive both in SHCC and ICC, whereas glial fibrillary acid protein (GFAP)-positive stromal cells were significantly more increased in ICC than in SHCC. SHCC clearly differed from HCC with respect to collagen types I, III and MMP-7 expression, and from ICC with regard to stromal components including laminin-5, tenascin-C and GFAP(+) stromal cells.

Immunohistological evaluation of single small hepatocellular carcinoma with negative staining of monoclonal antibody Hepatocyte Paraffin 1

The sensitivity and specificity of the monoclonal antibody Hepatocyte Paraffin 1 (Hep Par 1) for hepatocellular carcinoma (HCC) are very high, and the usefulness for differential diagnosis of hepatic tumors has been reported. However, there are some cases of HCC with negative staining for Hep Par 1. We examined the histopathological features of HCC with negative staining for Hep Par 1. We examined 69 samples of single nodular HCC less than 2 cm in greatest dimension, resected from 1985 to 1994 in our hospital, with immunohistological staining for Hep Par 1, cytokeratin 19 (CK 19), MUC-1 glycoprotein (MUC-1), and epithelial membrane antigen (EMA). Hep Par 1 staining was positive in 64 cases (93%) and negative in 5 cases (7%). With regard to the histological structure, 3 of the 5 negative cases were scirrhous HCC. With regard to the grade of histological differentiation, 2 cases were poorly differentiated HCC, 3 cases were moderately differentiated HCC, and no well-differentiated HCC was found in the negative cases. CK 19, MUC-1, and EMA staining were negative in all cases. It is necessary to recognize the existence of Hep Par 1 negative HCC, in particular scirrhous HCC. This may be due to a different mechanism in the earlier stage of hepatocarcinogenesis.

Spin-echo and dynamic gadolinium-enhanced FLASH MR imaging of hepatocellular carcinoma: correlation with histopathologic findings.

Evaluation of histologic subtype and degree of differentiation in hepatocellular carcinoma (HCC) is essential because it affects patient prognosis and treatment planning. To evaluate the histologic subtype of HCC with magnetic resonance (MR) imaging, conventional spin-echo and dynamic studies were correlated with histopathologic and angiographic findings in 72 HCCs. Dynamic MR imaging was performed with the fast low-angle shot (FLASH) technique after administration of gadopentetate dimeglumine. There was considerable overlap in signal intensity between various tumor grades on both T1- and T2-weighted images. On dynamic MR images, the peak contrast enhancement ratio correlated with tumor grade (well-differentiated, 29.5 +/- 24.7; moderately differentiated, 63.5 +/- 24.1; poorly differentiated, 86.9 +/- 26.4) or degree of dilatation of the sinusoidlike vascular space between tumor cells. The maximum contrast-to-noise ratio in tumor (relative to surrounding liver) was achieved within 60 seconds in 45 HCCs (mostly of the trabecular or pseudoglandular type). Enhancement was slight or minimal in 17 tumors (mostly small, well-differentiated tumors). In 10 tumors, the degree of enhancement increased with time, with maximum enhancement in the delayed phase (most frequently in scirrhous HCC). These dynamic patterns correlated with angiographic findings. These data indicate that the degree and pattern of enhancement on dynamic MR images reflect tumor differentiation and architecture of HCC.

Clinicopathological study on combination therapy consisting of arterial infusion of lipiodol-dissolved SMANCS and transcatheter arterial embolization for hepatocellular carcinoma.

Combination therapy (LpTAE) consisting of arterial infusion of a lipophilic anticancer drug, SMANCS, dissolved in an oily lymphographic agent, lipiodol (LPD), and transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) was studied with special reference to the pathological findings. A total of 32 patients were subjected to surgical resection after LpTAE. The pattern of LPD deposition in the tumor was examined by CT scan (Lipiodol CT, LpCT) at 7 days and/or 1 month after LpTAE. The resected materials were examined radiographically with soft X-rays and histologically. LPD was deposited in tiny daughter nodules with a diameter of less than 5 mm and in tumor thrombi as well as in the main tumors, which showed necrotic change. Part of the LPD flowed out from the main tumor via the drainage vein and was deposited in the capsular invasion, resulting in necrosis. LPD accumulated almost exclusively within the blood spaces of trabecular-type HCC, creating a pattern corresponding to a cast of the tumor vessels, which showed prominent necrosis. On the other hand, LPD was not deposited in scirrhous, compact, or well-differentiated HCC, which showed little or no necrosis. It was demonstrated that LpCT images, which accurately depicted the existence and the extent of LPD deposition and necrosis in the tumor, were useful for precise evaluation of the therapeutic effect. Our findings indicate that LpTAE and LpCT are valuable for the diagnosis and treatment of HCC and should play a central role in systemic therapeutic approaches to this disease.