OBJECTIVETo study the clinicopathologic features of combined hepatocellular-cholangiocarcinoma (cholangiolocellular type, CLC type) with stem cell features and its relationship to hepatic progenitor cells (HPCs).

METHODSClinical and histologic features of 26 cases of combined hepatocellular-cholangiocarcinoma (CLC type) were reviewed. Histochemistry was performed to confirm the type of mucin and immunohistochemical study was carried out for hepatocytic markers (Hep Par-1 and AFP) and biliary/HPCs markers (CK7, CK9, EMA, EpCAM, NCAM, CKIT).

RESULTSThe age of patients ranged from 51 to 82 years (mean 64 years). All 26 cases contained CLC and hepatocellular carcinoma components. CLC area was composed of mixtures of small monotonous glands with abundant fibrous stroma and lymphocytic infiltrate. Tumor cells were cuboidal, smaller in size than normal hepatocytes, with basophilic cytoplasm and round nuclei. All cases, especially at the tumor boundary, showed HCC-like trabecular areas characterized by mildly atypical tumor cells with abundant eosinophilic cytoplasm and little stroma. Out of 26 cases, 21 showed definite glandular formation with mucin production, representing intrahepatic cholangiocarcinoma areas. The three distinct areas showed transitional zones merging with each other. The surrounding liver tissue showed cirrhosis and chronic hepatitis with varying degrees of fibrosis and periportal ductular reaction. Immunohistochemistry showed that biliary/HPC markers (CK7, CK9, EMA, EpCAM, NCAM and CKIT) were strongly positive in CLC area in almost all cases, similar to the staining pattern of ductular reaction. In HCC-like areas, CK7 and CK19 were positive in all cases and the expression rates of EMA, EpCAM, NCAM, CKIT, AFP, Hep Par-1 were 80.8% (21/26), 88.5% (23/26), 84.6% (22/26), 88.5% (23/26), 46.2% (12/26) and 53.8% (14/26) respectively, similar to the staining pattern of intermediate hepatocytes. In ICC areas, CK7, CK9, EMA and EpCAM were positive in all cases without the expression of NCAM and CKIT.

CONCLUSIONThe clinicopathologic findings and immunohistochemical results in this study highly suggest a hepatic progenitor cell origin of combined hepatocellular-cholangiocarcinoma (CLC type).

Bile Duct Neoplasms ; pathology ; Biomarkers ; metabolism ; Carcinoma, Hepatocellular ; pathology ; Cholangiocarcinoma ; pathology ; Hepatocytes ; cytology ; Humans ; Immunohistochemistry ; Liver Cirrhosis ; pathology ; Liver Neoplasms ; pathology ; Mucins ; metabolism ; Stem Cells ; cytology

No abstract available.
Aged ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Cadherins/metabolism ; Cholangiocarcinoma/*pathology/radiography ; Female ; Giant Cells/metabolism/*pathology/radiography ; Humans ; Osteoclasts/pathology ; Tomography, X-Ray Computed

No abstract available.
Bile Ducts, Intrahepatic ; Cell Differentiation ; Cholangiocarcinoma/*pathology ; Humans ; Immunohistochemistry ; Keratin-19/metabolism ; Liver Neoplasms/*pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed

OBJECTIVETo study the correlation between clinicopathological features and serum carbohydrate antigen 19-9 (CA19-9)/carcinoembryonic antigen (CEA) in patients with extrahepatic cholangiocarcinoma (ECC).

METHODSThe clinicopathological data of 126 cases of extrahepatic cholangiocarcinoma treated in our department from Jan. 1999 to Dec. 2012 were collected and analyzed in this study. The correlation between clinicopathological features and sensitivity of CA19-9/CEA was analyzed by chi-square test. The correlation of clinicopathological features and value of serum CA19-9/CEA was analyzed by t test and F test.

RESULTSThe average value of CA19-9 before surgery in the 126 patients was 595.3 U/ml. The values of CA19-9 in 91 patients were abnormal and the sensitivity of CA19-9 was 72.2%. The average value of CEA before surgery was 12.6 U/ml. The value of CEA in 26 patients were abnormal and the sensitivity of CEA was 20.6%. The values of combined detection of serum CA19-9 and CEA before surgery were abnormal in a total of 97 cases with a sensitivity of 77.0%. There was no significant correlation between clinicopathological features and sensitivity of CA19-9 (P > 0.05). The location of tumor was significantly correlated to the diagnostic sensitivity of CEA. The sensitivity of CEA to distal ECC was only 15.4%. The value of CA19-9 was relatively high in patients >60-year old or with neural invasion, while CEA was higher when tumor was located in the middle of bile duct (P < 0.05). There was no significant difference of serum CA19-9 before and after jaundice reduction (P > 0.05).

CONCLUSIONSThe diagnostic sensitivity of CA19-9 is not affected by gender, age, blood type, tumor location, degree of differentiation, tumor size, T stage, vascular tumor thrombus, lymph node metastasis, perineural invasion, and preoperative jaundice. However, the diagnostic sensitivity of CEA is affected by tumor location. The value of CA19-9 is correlated with tumor invasion and is relatively high in patients above 60 years old.

Bile Duct Neoplasms ; metabolism ; pathology ; Bile Ducts, Intrahepatic ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; CA-19-9 Antigen ; metabolism ; Carcinoembryonic Antigen ; metabolism ; Cholangiocarcinoma ; metabolism ; pathology ; Humans ; Lymphatic Metastasis

OBJECTIVETo explore the clinicopathological features and prognostic factors of three rare and poor-prognostic pathological subtypes of primary liver carcinoma, and improve the clinical diagnosis and surgical treatment.

METHODSA retrospective analysis of clinicopathological data of 69 patients with rare pathological subtypes of primary liver carcinoma, diagnosed by postoperative pathology in our hospital from October 1998 to June 2013 was carried out. The data of 80 cases of common poorly differentiated hepatocellular carcinoma treated in the same period were collected as control group. Kaplan-Meier method was used to analyze the survival rate, and Cox proportional hazards model was used for prognostic analysis in the patients.

RESULTSThirty-four cases were combined hepatocellular carcinoma and cholangiocarcinoma (CCC, 28 males, 6 females), with a median age of 52 years (range, 33 to 73). Ninteen cases were giant cell carcinoma (GCC, 16 males and 3 females), with a median age of 59 years (range, 38 to 66). Sixteen cases were sarcomatoid carcinoma (SC, 14 males and 2 females), with a median age of 57 years (range, 46 to 70). The survival analysis revealed that median survival time and the 1-, 3-, 5-year survival rates for these 3 groups were 20 months, 61.8%, 29.4%, and 20.6% in the CCC patients, 13 months, 52.6%, 31.6%, and 0% in the GCC patients, and 8 months, 31.3%, 0%, 0% in the SC patients, respectively. The median survival time and survival rate of the SC group were significantly lower than those of the other three groups (P < 0.05). However, in the SC group, the incidences of hilar lymph nodes metastasis, vascular tumor emboli and invasion of adjacent organs were significantly higher than those in the other three groups (P < 0.05). There were no statistically significant differences among the other three groups (P > 0.05). The levels of carcino-embryonic antigen were higher in the three rare subtype groups than that of the control group. The incidences of multiple tumors of the three rare subtype groups were higher than that of the control group (P < 0.05). Positive surgical margin was an independent unfavorable prognostic factor.

CONCLUSIONSThe combined hepatocellular carcinoma and cholangiocarcinoma, giant cell carcinoma and sarcomatoid carcinoma have a poor prognosis. Among them sarcomatoid carcinoma is the most malignant and poor prognostic one. Radical resection is recommended.

Adult ; Aged ; Carcinoembryonic Antigen ; metabolism ; Carcinoma, Giant Cell ; metabolism ; pathology ; surgery ; Carcinoma, Hepatocellular ; metabolism ; pathology ; surgery ; Carcinosarcoma ; metabolism ; pathology ; surgery ; Cholangiocarcinoma ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Hepatectomy ; methods ; Humans ; Liver Neoplasms ; metabolism ; pathology ; surgery ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplastic Cells, Circulating ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Survival Rate

Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability to differentiate histologically into two distinct tumor types. Bi-phenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although a rare tumor, is important for clinicians to recognize, since treatment options targeting both elements of the tumor are crucial. Imaging findings of bi-phenotypic HCC-CC are not specific and include features of both HCC and CC. A combination of imaging and immuno-histochemical analysis is usually needed to make the diagnosis.
CA-19-9 Antigen/metabolism ; Carcinoma, Hepatocellular/mortality/pathology/radiography ; Cholangiocarcinoma/mortality/pathology/radiography ; Humans ; Liver Neoplasms/mortality/pathology/*radiography ; Magnetic Resonance Imaging ; Phenotype ; Risk Factors ; Survival Analysis ; Tomography, X-Ray Computed ; alpha-Fetoproteins/analysis

BACKGROUND/AIMS: Biliary drainage is performed in many patients with cholangiocarcinoma (CCA) to relieve obstructive jaundice. For those who have undergone biliary drainage, bile cytology can be easily performed since the access is already achieved. This study aims to determine the clinical usefulness of bile cytology for the diagnosis of CCA and to evaluate factors affecting its diagnostic yield. METHODS: A total of 766 consecutive patients with CCA underwent bile cytology via endoscopic nasobiliary drainage or percutaneous transhepatic biliary drainage from January 2000 to June 2012. Data were collected by retrospectively reviewing the medical records. We evaluated the diagnostic yield of bile cytology with/without other sampling methods including brush cytology and endobiliary forcep biopsy, and the optimal number of repeated bile sampling. Several factors affecting diagnostic yield were then analyzed. RESULTS: The sensitivity of bile cytology, endobiliary forceps biopsy, and a combination of both sampling methods were 24.7% (189/766), 74.4% (259/348), and 77.9% (271/348), respectively. The cumulative positive rate of bile sampling increased from 40.7% (77/189) at first sampling to 93.1% (176/189) at third sampling. On multivariate analysis, factors associated with positive bile cytology were perihilar tumor location, intraductal growing tumor type, tumor extent > or =20 mm, poorly differentiated grade tumor, and three or more samplings. CONCLUSIONS: Although bile cytology itself has a low sensitivity in diagnosing CCA, it has an additive role when combined with endobiliary forceps biopsy. Due to the relative ease and low cost, bile cytology can be considered a reasonable complementary diagnostic tool for diagnosing CCA.
Aged ; Bile/*cytology ; Bile Duct Neoplasms/*diagnosis/pathology/radiography ; CA-19-9 Antigen/metabolism ; Cholangiocarcinoma/*diagnosis/pathology/radiography ; Drainage ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Retrospective Studies

BACKGROUND/AIMS: To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. METHODS: An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. RESULTS: The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. CONCLUSIONS: CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.
Aged ; Bile Duct Neoplasms/metabolism/*pathology ; Bile Ducts, Intrahepatic/metabolism/*pathology ; Case-Control Studies ; Cell Line, Tumor ; Cell Proliferation ; Cholangiocarcinoma/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/metabolism/pathology ; RNA Interference/*physiology ; RNA, Small Interfering/metabolism ; Receptors, CXCR4/antagonists & inhibitors/*metabolism ; Tumor Cells, Cultured

No abstract available.
Aged ; Bile Duct Neoplasms/metabolism/*pathology ; Bile Ducts, Intrahepatic/metabolism/*pathology ; Cholangiocarcinoma/metabolism/*pathology ; Humans ; Immunohistochemistry ; Keratin-19/metabolism ; Male ; Positron-Emission Tomography ; Tomography, X-Ray Computed

OBJECTIVETo investigate clinicopathological features of combined hepatocellular-cholangiocarcinoma (C-HCC-CC) with neuroendocrine carcinoma (NEC) differentiation and to review the literature.

METHODSThe clinical data, histological manifestations and immunohistochemical staining results of two cases of C-HCC-CC were analyzed along with a review of the current literature.

RESULTSBoth patients were male with an average age of 57.5 years. Both patients were positive for hepatitis B virus antigen. The tumors of both cases demonstrated the following 3 unequivocal mixed elements: (1) polygonal epithelial tumor cells growing in nests or trabeculae with positive staining for Hepatocyte and AFP, diagnostic of hepatocellular carcinoma (HCC). Cytoplasmic bile production was present in the tumor cells in one case; (2) elliptic or short spindle-shape small blue tumor cells growing in nests or organoid pattern with Syn/CgA/CD56 positivity confirming the presence of neuroendocrine carcinoma (NEC) component; (3) oval tumor cells growing in nests or glandular forms with positivity of CK19 and CK7 confirming differentiation of cholangiocarcinoma (CC). In both cases, the tumors contained at least 20% of each of HCC, NEC and CC components.

CONCLUSIONC-HCC-CC with NEC is a rare form of primary malignancy of the liver with a poor prognosis.

Bile Duct Neoplasms ; Bile Ducts, Intrahepatic ; Bone Neoplasms ; secondary ; CD56 Antigen ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; therapy ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; therapy ; Chemoembolization, Therapeutic ; Cholangiocarcinoma ; metabolism ; pathology ; therapy ; Chromogranin A ; metabolism ; Humans ; Immunohistochemistry ; Keratin-19 ; metabolism ; Keratin-7 ; metabolism ; Ki-67 Antigen ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; therapy ; Male ; Middle Aged ; Mixed Tumor, Malignant ; metabolism ; pathology ; therapy ; Synaptophysin ; metabolism ; alpha-Fetoproteins ; metabolism