Resected case of a double cancer,a hepatocellular carcinoma and a cholangiocellular carcinoma,and their spread to the skin

Combined hepatocellular and cholangiocellular carcinomas are rare. Moreover, double cancer cases of hepatocellular carcinoma and cholangiocellular carcinoma are very rare. This report describes a patient with double cancer. A correct clinical diagnosis was made with successful resection, and cutaneous metastases occurred near the exit site of an abdominal drain after the resection of the tumor. The patient, a 66-year-old man with chronic hepatitis C, was admitted to our hospital because he was suspected of having primary liver cancer. Two liver masses in the anteroinferior segment were detected by using angiography, computed tomography during angiography, and computed tomography during arterioportography. These clinical findings indicated that the tumor in the right lobe was hepatocellular carcinoma. A resection of the S5 subsegmentectomy was performed. One mass was diagnosed histologically as hepatocellular carcinoma, and the other mass was diagnosed as cholangiocellular carcinoma. One year after the operation, the patient palpated a hard subcutaneous nodule 4.0 cm in diameter in the right lower abdominal wall. A subcutaneous tumor was excised, and a histological examination revealed moderately differentiated hepatocellular carcinoma. The patient is currently doing well without further recurrence of hepatocellular carcinoma or cholangiocellular carcinoma, 18 months after subsegmentectomy and six months after excision of the subcutaneous tumor.     

A clinical study of 11 cases of combined hepatocellular-cholangiocarcinoma Assessment of enhancement patterns on dynamics computed tomography before resection.

BACKGROUND AND AIM:: The aim of this study was to identify computed tomography features that contribute to clinical diagnosis of hepatocellular-cholangiocarcinoma. METHODS:: We retrospectively reviewed the clinicopathologic features of 11 patients who underwent hepatectomy for hepatocellular-cholangiocarcinoma between January 1994 and December 2003 at Hiroshima City Hospital and investigated correlation of histopathologic features of surgical specimens with preoperative enhanced computed tomography findings. RESULTS:: Three computed tomography enhancement patterns were observed: an area of hyperenhancement in the early phase and hypoenhancement due to washout of contrast medium in the late phase, resembling hepatocellular carcinoma (Type I, n=4); peripheral enhancement in the early and late phases (Type II, n=2); an area of hyperenhancement in the early phase and an area of slight delayed enhancement in the late phase (Type III, n=4). Histopathologically, all tumors were of mixed morphology (Allen's Type C) comprising hepatocellular carcinoma and cholangiocarcinoma components with transitional features. Computed tomography findings conformed well to pathologic findings. The hepatocellular carcinoma component was predominant in Type I masses. Type II masses showed central necrosis. In Type III masses, the hepatocellular carcinoma-predominant component corresponded to the area of early-phase enhancement and the cholangiocarcinoma-predominant component to the area of late-phase enhancement. CONCLUSIONS:: In Type III tumors, hepatocellular and cholangiocellular components can be identified on the basis of dynamic computed tomography enhancement pattern.     

Occurrence of hepatocellular and cholangiocellular carcinoma in different hepatic lobes

Separate hepatocellular and cholangiocellular carcinoma (double cancer) in the liver are extremely rare subtypes of primary hepatic carcinomas. We report a case of double primary liver carcinomas that were surgically resected simultaneously. A 66-year-old man was admitted because of elevation of serum levels of alpha-fetoprotein. Abdominal computed tomography and angiography showed two hypervascular masses in S4 and S8 hepatic segments. With the diagnosis of multiple hepatocellular carcinomas, the tumors were surgically resected. Histological examination showed that the tumor in S4 segment was moderately differentiated cholangiocellular carcinoma, the other in S8 segment was trabecular, moderately differentiated hepatocellular carcinoma. Immunohistochemically, a positive staining in carcinoembyonic antigen and cytokeratin 7 supported the diagnosis of cholangiocellular carcinoma for the tumor in S4 segment. The frequency of double cancer in the liver is much lower than mixed or combined cancer (0.1-0.5%). The different epithelial malignant tumors of hepatocellular carcinoma and cholangiocellular carcinoma, which were located in different hepatic lobes and resected simultaneously, has been reported in only two cases including the present case.     

数字减影血管造影对原发性肝癌的术前评价

目的评价数字减影血管造影（DSA）对我国原发性肝癌术前的意义。方法回顾分析1998年5月～2007年5月1000例原发性肝癌术前的DSA影像与多层螺旋CT（MSCT）及彩超检查结果。结果三种方法发现肝癌1000例,直径3em以上的700例肝癌中,DSA发现670例;240例小肝癌中DSA发现202例;30例弥漫性肝癌中,DSA发现28例;900个子灶中,DSA发现890个;440例门脉癌栓中,DSA发现362例;490例动静脉瘘、动门脉瘘中,DSA发现482例。结论DSA检查对原发性肝癌的术前评价具有不可替代的作用。     

Budd-Chiari syndrome as the primary manifestation of a fibrolamellar hepatocellular carcinoma.

An 18-year-old female patient was admitted with ascites, right upper abdominal tenderness and peripheral edema. Angiography showed complete occlusion of the vena cava inferior up to the level of the right atrium. By open heart surgery, masses of thrombotic material were pulled out of the v. cava inferior/vv. iliacae which histologically contained tumor cell populations consistent with a hepatocellular carcinoma. Celiacography showed a highly vascularized tumor in the right hepatic lobe. Histologically, it proved to be fibrolamellar subtype hepatocellular carcinoma.     

Hyperplastic foci reflect the risk of multicentric development of human hepatocellular carcinoma

Background/Aims: Identification of the risk factors of multicentric hepatocarcinogenesis is important for the clinical management of hepatocellular carcinoma. We investigated hyperplastic foci in non-cancerous liver parenchyma, and clarified their pathological features and clinical significance.Methods: Hyperplastic foci were defined as hypercellular areas, which architecturally and cytologically resembled early hepatocellular carcinoma or adenomatous hyperplasia but did not form macroscopically detectable nodules. Surgically resected livers from 155 patients with hepatocellular carcinoma were examined histopathologically and immunohistochemically.Results: Hyperplastic foci were found in 26 of 155 patients (16.8%). All the patients with hyperplastic foci had chronic liver diseases, and the incidence did not differ between those with chronic hepatitis and those with liver cirrhosis. Six of 92 (6.5%) patients with single primary hepatocellular carcinoma nodules, 8 of 42 (19.0%) with two nodules, and 12 of 21 (57.0%) with more than three nodules had hyperplastic foci. The incidence of hyperplastic foci showed a significant positive correlation with the multiplicity of hepatocellular carcinoma nodules. Immunohistochemically, hyperplastic foci were masses of proliferative hepatocytes similar to adenomatous hyperplasia and early hepatocellular carcinoma.Conclusions: Hyperplastic foci reflect the risk of multicentric hepatocarcinogenesis. Our results suggest strongly that hyperplastic foci are precursors of adenomatous hyperplasia or hepatocellular carcinoma.     

Two cases of spontaneous regression of multicentric hepatocellular carcinoma after intraperitoneal rupture: possible role of immune mechanisms

We report two cases of spontaneous regression of hepatocellular carcinoma. Firstly, a 64-year-old man with alcohol related cirrhosis developed multiple liver tumours with elevation of the alpha-fetoprotein level at 915 ng/ml. A spontaneous regression of all the tumoural masses but one and normalization of the alpha-fetoprotein level was observed after intraperitoneal spread of the malignancy. Resection of the remaining tumour 9 months later confirmed a hepatocellular carcinoma. Secondly, a 70-year-old woman with alcohol related cirrhosis developed multiple liver tumours with elevation of the alpha-fetoprotein level to 4000 ng/ml; a regression of all the tumoural masses but one and a decrease of the alpha-fetoprotein level to 400 ng/ml was observed after intraperitoneal spread of the malignancy and treatment with tamoxifen. We discuss a possible immune mechanism of tumoural regression with a review of similar cases described in the literature.     

MR imaging of hepatocellular carcinoma at 1.5 Tesla.

The authors investigated the magnetic resonance appearance of hepatocellular carcinoma using a 1.5-Tesla magnet. Twenty-four patients with pathologically proven hepatocellular carcinoma had magnetic resonance imaging (MRI) studies, which were retrospectively reviewed. All patients were imaged with at least two of the following techniques: (1) T1-weighted (T1W), (2) T1-weighted with Gd-DTPA enhancement (T1W-E), (3) T2-weighted (T2W), (4) proton density (PD), and (5) gradient-recalled echoes (GRE). T1W images were equal to T2W images for tumor detection using a grading system. T1W images were slightly better than T2W images for the total number of lesions detected. The other pulsing techniques (PD, T1W-E, and GRE) detected fewer lesions. Eight cases of hepatocellular carcinoma (33%) had nonhomogeneous increased signal intensity on both T1W and T2W images. The authors conclude that T1W images are equal to T2W images for detection of hepatocellular carcinoma. The authors also conclude that 33% of hepatocellular carcinomas have an imaging pattern with increased signal intensity on both T1W and T2W images. This pattern is atypical for most other hepatic masses and hence can be used to suggest the mass is hepatocellular carcinoma.     

Association of hepatocellular carcinoma and a hyperplastic nodule after phosphate diethylstilbestrol therapy

We treated a patient in whom a hepatocellular carcinoma and a hyperplastic nodule of the liver concomitantly grew in association with long term phosphate diethylstilbestrol therapy for a carcinoma of the prostate. A 72-year-old Japanese man was admitted for investigation of hepatic masses. A diagnosis of prostate carcinoma had been made seven years ago and phosphate diethylstilbestrol 200mg daily had been prescribed. A small mass was first detected in the liver four years later and another mass appeared three years after the appearance of the first mass. Histology of the excised tissue showed the former mass to be a hyperplastic nodule and the latter one hepatocellular carcinoma. Findings of cirrhosis, hepatitis or fibrosis were nil but fatty metamorphosis of the hepatocytes was apparent. These histological changes were considered to be associated with long-term phosphate diethylstilbestrol therapy therefore careful follow-up using imazing diagnosis is recommended for patients on phosphate diethylstilbestrol therapy.     

Association of hepatocellular carcinoma and a hyperplastic nodule after phosphate diethylstilbestrol therapy

We treated a patient in whom a hepatocellular carcinoma and a hyperplastic nodule of the liver concomitantly grew in association with long term phosphate diethylstilbestrol therapy for a carcinoma of the prostate. A 72-year-old Japanese man was admitted for investigation of hepatic masses. A diagnosis of prostate carcinoma had been made seven years ago and phosphate diethylstilbestrol 200 mg daily had been prescribed. A small mass was first detected in the liver four years later and another mass appeared three years after the appearance of the first mass. Histology of the excised tissue showed the former mass to be a hyperplastic nodule and the latter one hepatocellular carcinoma. Findings of cirrhosis, hepatitis or fibrosis were nil but fatty metamorphosis of the hepatocytes was apparent. These histological changes were considered to be associated with long-term phosphate diethylstilbestrol therapy therefore careful follow-up using amazing diagnosis is recommended for patients on phosphate diethylstilbestrol therapy.     

Imaging of hepatic steatosis

Hepatic steatosis is a common finding encountered during cross-sectional imaging examinations. This article reviews the imaging findings of hepatic steatosis as revealed by sonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy. Focal fatty sparing and focal hepatic steatosis are conditions that can create potential diagnostic challenges for the radiologist. The typical findings, distribution, and etiology of these focal processes are presented. In the setting of diffuse hepatic steatosis, hepatic mass lesions can be difficult to discern on both computed tomography and sonography, with reported decreased sensitivity and specificity of lesion detection. In such cases, magnetic resonance imaging may be the imaging procedure of choice for the detection and characterization of both hepatic steatosis and coexistent hepatic masses. Some hepatocellular neoplasms, particularly hepatic adenoma and well-differentiated hepatocellular carcinoma, can have intratumoral lipid. By demonstrating the lipid content of these masses, imaging can add specificity in characterizing them as hepatocellular in origin because nonhepatocellular neoplasms in general do not contain intracellular lipid.     

Ultrasonographic evaluation of portal blood flow using transhepatic carbon dioxide injection.

BACKGROUND/AIMS: The evaluation of portal blood flow in hepatic mass is important for the diagnosis of hepatocellular carcinoma. We have designed a new method to easily evaluate portal blood flow in hepatic mass using ultrasonography with injection of carbon dioxide into the intrahepatic portal vein by direct puncture with a fine needle. METHODOLOGY: We evaluated 29 masses in the liver of 20 patients ultrasonically with injection of carbon dioxide into the intrahepatic portal vein. RESULTS: Of 29 space-occupying lesions (SOLs), 13 were found to have portal blood flow and 16 were found to have no portal flow by this method. All 15 SOLs which had no portal flow were histologically confirmed to be hepatocellular carcinoma. Of 13 SOLs with portal flow, 5 were confirmed to be hepatocellular carcinoma. For 7 of 9 SOLs in which both this method and arterial portographic computed tomography were performed, the results were in agreement. CONCLUSIONS: Ultrasonographic evaluation of portal blood flow using transhepatic carbon dioxide injection appears to be useful for the evaluation of portal flow in mass and may aid in the diagnosis and management of mass in patients with liver disease.     

Hepatocellular carcinoma developed in a patient with chronic hepatitis C after the disappearance of hepatitis C virus due to interferon therapy.

A 62 year-old man was admitted to Asahikawa Medical College Hospital. Injection therapy of natural interferon-alpha was performed against chronic active hepatitis with hepatitis C virus infection. He successfully responded to interferon therapy with normalization of serum transaminases and disappearance of serum hepatitis C virus RNA. The liver function test remained within normal limits and serum hepatitis C virus RNA was not detected throughout the observation period. Three years later, CT examination demonstrated 2 small hepatic masses. Ultrasound-guided biopsy of the hepatic mass demonstrated well-differentiated hepatocellular carcinoma histologically. Laparoscopic examination revealed chronic hepatitis, but neither active inflammation nor cirrhotic changes were noted as an underlying liver disease. In the liver specimen, hepatitis C virus RNA was not detected by RT-PCR. Percutaneous ultrasound-guided ethanol injection therapy achieved complete necrosis of the hepatocellular carcinoma and there was no recurrence of hepatic cancer during the follow-up period. This case suggests that patients with chronic hepatitis C infection, who have complete disappearance of serum hepatitis C virus RNA by interferon therapy, should be followed-up carefully for the potential development of hepatocellular carcinoma.     

Hepatic mucosa-associated lymphoid tissue lymphoma and hepatocellular carcinoma in a patient with hepatitis B virus infection

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare disease. A 65-year-old female patient with chronic hepatitis B presented with multiple solid masses in segment (S) 4, S5, and S6 of the liver. The nodule in S5 was diagnosed preoperatively as hepatocellular carcinoma by computed tomography, magnetic resonance imaging, and angiography. The nodule in S4 was initially interpreted as lymphoid follicles by needle biopsy. Segmentectomy of S5 and partial resection of S6 were performed. Microscopic examination of the S5 nodule revealed moderately differentiated hepatocellular carcinoma. The nodule from S6 showed nodular proliferation of atypical intermediate to medium-sized lymphoid cells in the portal area and lymph epithelial lesions of bile ducts. The atypical lymphoid cells were positive for LCA, L-26 and bcl-2 and negative for UCHL-1. These features were consistent with the diagnosis of MALT lymphoma. This is the first case report of synchronous hepatic MALT lymphoma and hepatocellular carcinoma associated with chronic hepatitis B.     

Hepatocellular carcinoma in a patient with focal nodular hyperplasia

BackgroundFocal nodular hyperplasia is an uncommon liver tumour that typically requires no therapeutic intervention.Case outlineA 43-year-old woman with a 20-year history of oral contraceptive use presented with symptomatic bilateral liver masses. Biopsy revealed hepatocellular carcinoma in the right hemiliver and focal nodular hyperplasia in the left hemiliver.At operation,the patient was noted to have multiple liver nodules bilaterally, and all intraoperative biopsies were consistent with focal nodular hyperplasia including a biopsy taken from the region that demonstrated carcinoma preoperatively. Because of the earlier biopsy results and the patient''s preoperative symptoms, a right hemihepatectomy was performed. Final pathology revealed hepatocellular carcinoma directly adjacent to an area of focal nodular hyperplasia, as well as multiple other areas of hyperplastic liver tumour.DiscussionAlthough focal nodular hyperplasia is believed to be benign, few studies have followed patients with this tumour beyond three years. Longer-term follow-up studies are needed to determine the natural history of focal nodular hyperplasia, potentially focussing on a subset of patients with either diffuse tumours or prolonged oral contraceptive use.     

A qualitative signature for early diagnosis of hepatocellular carcinoma based on relative expression orderings

Background & Aims

Currently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate.

Methods

Based on the within‐sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non‐tumour tissues from cirrhosis tissues of non‐hepatocellular carcinoma patients.

Results

A signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non‐hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non‐hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long‐lasting cirrhosis could have already gained hepatocellular carcinoma characteristics.

Conclusions

The signature can distinguish both hepatocellular carcinoma tissues and tumour‐adjacent tissues from cirrhosis tissues of non‐hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early diagnosis of hepatocellular carcinoma.     

Synchronous Primary Lung Adenocarcinoma and Hepatocellular Carcinoma Successfully Treated with a Combination of Atezolizumab,Bevacizumab, Carboplatin,and Paclitaxel

Chemotherapy for multiple primary malignancies is challenging. We herein report a case of synchronous primary lung adenocarcinoma and hepatocellular carcinoma (HCC). A 72-year-old man was admitted for the evaluation of an abnormal shadow on his lung. Computed tomography revealed a lung nodule in the right upper lobe and multiple liver masses. He was diagnosed with synchronous primary lung adenocarcinoma and HCC. Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) chemotherapy was efficacious for both tumors. ABCP chemotherapy may be a potential treatment option for synchronous primary lung adenocarcinoma and HCC.     

Helicobacter pylori and hepatocellular carcinoma: Correlated or uncorrelated?

Helicobacter pylori can be detected in liver tissue resected from patients with hepatocellular carcinoma. Conflicting reports regarding the relationship between H. pylori and hepatocellular carcinoma mean it is uncertain whether H. pylori acts as a troublemaker, co-risk factor or innocent bystander to the development of hepatocellular carcinoma. Clinical studies in patients without known causes of hepatocellular carcinoma are important to discover whether H. pylori is involved in the carcinogenesis of hepatocellular carcinoma. High quality prospective studies in patients with hepatocellular carcinoma, hepatitis C virus infection and no cirrhosis are needed to determine whether H. pylori is a co-risk factor for hepatocellular carcinoma.     

Different 18F-FDG imaging: A rare case of liver multiple carcinomas

A 49-year-old man was referred to the hospital with the complaints of haematochezia and weight loss. Colonoscopy and pathological needle biopsy suggested moderately to highly differentiated adenocarcinoma. The patient underwent abdominal CT examination, which demonstrated two augmented and irregular masses in the liver. However, the glucose metabolism of 18F-FDG in these two lesions was completely different. Considering the different glucose metabolism, a needle biopsy of the liver mass was performed, and the diagnosis was rectal cancer with liver metastasis and primary hepatocellular carcinoma.     

Hepatocellular carcinoma presenting with obstructive jaundice: a clinicopathological study of eight cases

BACKGROUND/AIMS: The prognosis of icteric type hepatocellular carcinoma is extremely poor, not only because of obstructive jaundice, but also because of difficulties for early diagnosis. The aim of this study is to evaluate characteristics of icteric hepatocellular carcinoma for early diagnosis. METHODOLOGY: Eight patients with icteric hepatocellular carcinoma among 326 patients with hepatocellular carcinoma in our hospitals were retrospectively examined by laboratory data, image studies and pathology studies. RESULTS: Most cases were already advanced, with a portal tumor thrombus at the time of diagnosis. Imaging studies fail to reveal tumors because this type of hepatocellular carcinoma has an irregular faint margin and has lost the characteristic pattern of hepatocellular carcinoma, such as capsular formation or early enhancement. Pathology observations demonstrated poorly or moderately differentiated hepatocellular carcinoma in all our cases. CONCLUSIONS: This type of hepatocellular carcinoma should be considered in cirrhotic patients with obstructive jaundice or in patients with high tumor marker levels even if image studies fail to reveal tumors. For better prognosis, combination therapies such as biliary drainage, support for portal flow as well as treatment for the hepatocellular carcinoma, are necessary.