BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

No abstract available.
Adult ; Anterior Temporal Lobectomy ; Bile Duct Neoplasms/*diagnostic imaging/surgery ; *Bile Ducts, Intrahepatic/surgery ; Carcinoma, Hepatocellular/diagnostic imaging ; Cholangiocarcinoma/*diagnostic imaging/surgery ; Cholangiopancreatography, Magnetic Resonance ; Diagnosis, Differential ; Humans ; Liver/diagnostic imaging/metabolism ; Liver Neoplasms/diagnostic imaging ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed

Undifferentiated embryonal sarcoma of the liver (UESL) is rare primary hepatic sarcoma and is known to occur in pediatric patients. This case is the UESL occurred in a 51-year old male patient. Multilocular cystic lesion was composed of primitive spindle cells without specific differentiation. This rare case would help to review differential diagnosis of primary sarcoma in liver and cystic neoplasm of the liver.
Abdomen/diagnostic imaging ; Biomarkers, Tumor/blood ; Desmin/metabolism ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Liver Neoplasms/blood/*pathology/surgery ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Vimentin/metabolism

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.
Adenoma/*diagnosis/surgery ; Carcinoma, Hepatocellular/diagnosis ; Diagnosis, Differential ; Focal Nodular Hyperplasia/*diagnosis/surgery ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnosis/surgery ; beta Catenin/genetics/metabolism

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.
Adenoma/*diagnosis/surgery ; Carcinoma, Hepatocellular/diagnosis ; Diagnosis, Differential ; Focal Nodular Hyperplasia/*diagnosis/surgery ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnosis/surgery ; beta Catenin/genetics/metabolism

BACKGROUND/AIMS: To investigate sequential changes in laboratory markers after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) and the relationship of these changes to the severity of the underlying liver disease. METHODS: This retrospective analysis included 65 patients (44 males, 21 females) who underwent RFA of HCC. Hematologic and biochemical markers were assessed at the pre-RFA period and 1 day, 2-3 days, and 1-2 weeks after RFA. We classified the subjects into two groups: Child-Pugh A (n=41) and Child-Pugh B (n=24). The ablative margin volume (AMV) of each patient was measured. We analyzed the changes in laboratory profiles from the baseline, and investigated whether these laboratory changes were correlated with the AMV and the Child-Pugh classification. RESULTS: Most of the laboratory values peaked at 2-3 days after RFA. AMV was significantly correlated with changes in WBC count, hemoglobin level, and serum total bilirubin level (Pearson's correlation coefficient, 0.324-0.453; P<0.05). The alanine aminotransferase (ALT) level varied significantly over time (P=0.023). CONCLUSIONS: Most of the measured laboratory markers changed from baseline, peaking at 2-3 days. The ALT level was the only parameter for which there was a significant difference after RFA between Child-Pugh A and B patients: it increased significantly more in the Child-Pugh A patients.
Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase/blood ; Bilirubin/blood ; Biomarkers/metabolism ; Carcinoma, Hepatocellular/pathology/*surgery/ultrasonography ; Catheter Ablation ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms/pathology/*surgery/ultrasonography ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index

Hepatocellular carcinoma (HCC) is the fifth most common cancer in Korea. Diverse paraneoplastic syndromes can occur in patients with HCC, but parathyroid hormone-related peptide (PTH-rP)-induced hypercalcemia is uncommon. Hypercalcemia due to PTH or particularly PTH-rP-secreting HCC is associated with poor outcomes. We report a 71-year-old man who presented with symptoms of vague abdominal discomfort, somnolence, lethargy, nausea, vomiting, and weight loss. Imaging studies revealed a large HCC without metastasis. The laboratory findings showed elevated serum calcium level, low intact parathyroid hormone (iPTH) level and elevated PTH-rP level. These results led to a diagnosis of a PTH-rP-secreting HCC and paraneoplastic hypercalcemia. After emergency management of the hypercalcemia, the patient underwent an extended right hemihepatectomy with cholecystectomy. One year after the surgery, he is alive with normal calcium, PTH-rP, and iPTH levels. This case demonstrates that the rare phenomenon of life-threatening hypercalcemia caused by HCC should not be overlooked. These symptoms offer a good opportunity to diagnose HCC early. Radical tumor resection makes it possible to cure patients with PTH-rP-secreting HCC.
Aged ; Carcinoma, Hepatocellular/metabolism/pathology/*surgery ; Humans ; Liver Neoplasms/metabolism/pathology/*surgery ; Magnetic Resonance Imaging ; Male ; Parathyroid Hormone-Related Protein/metabolism/secretion ; Positron-Emission Tomography ; Tomography, X-Ray Computed

OBJECTIVETo study the clinical features, pathologic findings and prognosis of patients with dysplastic nodules of liver (DN) and early hepatocellular carcinomas (eHCC).

METHODSOne hundred and forty-five archival cases previously diagnosed as DN or eHCC or well-differentiated HCC during the period from 2000 to 2009 were retrieved and reevaluated with the new diagnostic criteria by two experienced pathologists, according to International Consensus Group for Hepatocellular Neoplasia (ICGHN) 2008. Immunohistochemical study (EnVision method) for CD34, HSP70, glutamine synthetase, glypican 3 and Ki-67 was carried out. The original diagnosis and diagnosis after review were compared and correlated with the survival data of the patients, with statistical analysis.

RESULTSWith the new criteria, 16 cases were diagnosed as low-grade DN, 50 cases as high-grade DN, 72 cases as DN with microinvasion, 7 cases as advanced HCC. Slide review showed no diagnostic discrepancy in 112 cases (77.2%). Amongst the 33 (22.8%) underdiagnosed cases, there were 7 cases of advanced HCC initially diagnosed as DN or DN with microinvasion and 26 cases of eHCC initially diagnosed as high-grade DN. Kaplan-Meier analysis showed that the diagnosis of high-grade DN or early HCC carried no statistically significant difference in overall survival (P = 0.778, 0.677) or disease-free survival (P = 0.949, 0.700) in all patients and in patients with no history of HCC. The co-existence of advanced HCC in patients with DN or eHCC significantly correlated with overall survival (P = 0.004) but not with disease-free survival (P = 0.079).

CONCLUSIONSThe new diagnostic criteria by ICGHN 2008 are useful in delineating high-grade DN and eHCC. The overall survival and disease-free survival of patients with eHCC or high-grade DN undergoing hepatectomy show no statistically significant difference. Patients with DN or eHCC have better prognosis than patients with advanced HCC, though there is still a high risk of tumor recurrence.

Antigens, CD34 ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; surgery ; Cell Transformation, Neoplastic ; Disease-Free Survival ; Female ; Follow-Up Studies ; HSP70 Heat-Shock Proteins ; metabolism ; Hepatectomy ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen ; metabolism ; Liver Cirrhosis ; metabolism ; pathology ; surgery ; Liver Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Survival Rate

Adult ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; surgery ; Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Chromogranin A ; metabolism ; Female ; Humans ; Keratin-7 ; metabolism ; Keratin-8 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Liver Neoplasms ; secondary ; Mixed Tumor, Malignant ; metabolism ; pathology ; surgery ; Nephrectomy ; Neprilysin ; metabolism ; Synaptophysin ; metabolism ; Vimentin ; metabolism

Adenocarcinoma, Clear Cell ; metabolism ; pathology ; surgery ; Alkaline Phosphatase ; metabolism ; Carcinoma, Endometrioid ; metabolism ; pathology ; Diagnosis, Differential ; Endodermal Sinus Tumor ; metabolism ; pathology ; surgery ; Female ; GPI-Linked Proteins ; metabolism ; Glypicans ; metabolism ; Humans ; Isoenzymes ; metabolism ; Keratin-7 ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; secondary ; Middle Aged ; Mucin-1 ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; surgery ; alpha-Fetoproteins ; metabolism