肝脏透明细胞癌.pdf

Primary clear cell carcinoma in the liver:CT and MRI findingsQing-Yu Liu,Ming Gao,Xiao-Feng Lin,Yong Li,Jian-Yu Chen,Department of Radiology,The Second Affiliated Hospital of Sun Yat-sen University,Guangzhou 510120,Guangdong Prov-ince,ChinaHai-Gang Li,Department of Pathology,The Second Affili-ated Hospital of Sun Yat-sen University,Guangzhou 510120,Guangdong Province,ChinaAuthor contributions:Liu QY designed the study and wrote the manuscript;Gao M,Li Y and Chen JY contributed to the analy-sis and interpretation of data;Li HG performed the pathological analysis;Lin XF contributed to the statistical analysis.Correspondence to:Qing-Yu Liu,PhD,Department of Radiol-ogy,The Second Affiliated Hospital of Sun Yat-sen University,107 Yan Jiang Xi Road,Guangzhou 510120,Guangdong Prov-ince,CTelephone:[phone] Fax:[phone]Received:August 29,2010 Revised:December 1,2010Accepted:December 8,2010Published online:February 21,2011AbstractAIM:To retrospectively analyze the computed tomogra-phy(CT)and magnetic resonance imaging(MRI)appear-ances of primary clear cell carcinoma of the liver(PCCCL)and compare the imaging appearances of PCCCL and com-mon type hepatocellular carcinoma(CHCC)to determine whether any differences exist between the two groups.METHODS:Twenty cases with pathologically proven PCCCL and 127 cases with CHCC in the Second Affili-ated Hospital of Sun Yat-sen University were included in this study.CT or MRI images from these patients were retrospectively analyzed.The following imaging findings were reviewed:the presence of liver cirrhosis,tumor size,the enhancement pattern on dynamic contrast scanning,the presence of pseudo capsules,tumor rup-ture,portal vein thrombosis and lymph node metastasis.RESULTS:Both PCCCL and CHCC were prone to occur in patients with liver cirrhosis,the association rate of liver cirrhosis was 80.0%and 78.7%,respectively(P 0.05).The mean sizes of PCCCL and CHCC tumors were(7.28 4.25)cm and(6.96 3.98)cm,respectively.Small HCCs were found in 25.0%(5/20)of PCCCL and 19.7%(25/127)of CHCC cases.No significant differ-ences in mean size and ratio of small HCCs were found between the two groups(P=0.658 and 0.803,respec-tively).Compared with CHCC patients,PCCCL patients were more prone to form pseudo capsules(49.6%vs 75.0%,P=0.034).Tumor rupture,typical HCC en-hancement patterns and portal vein tumor thrombosis were detected in 15.0%(3/20),72.2%(13/18)and 20.0%(4/20)of patients with PCCCL and 3.1%(4/127),83.6%(97/116)and 17.3%(22/127)of patients with CHCC,respectively.There were no significant differenc-es between the two groups(all P 0.05).No patients with PCCCL and 2.4%(3/127)of patients with CHCC showed signs of lymph node metastasis(P 0.05).CONCLUSION:The imaging characteristics of PCCCL are similar to those of CHCC and could be useful for dif-ferentiating these from other liver tumors(such as hem-angioma and hepatic metastases).PCCCLs are more prone than CHCCs to form pseudo capsules.2011 Baishideng.All rights reserved.Key words:Clear cell carcinoma;Hepatocellular carcino-ma;Pathology;Magnetic resonance imaging;Computed Tomography;X-rayPeer reviewers:C Triantopoulou,MD,PhD,Head of Radiology Department,Konstantopouleio general Hospital,3-5,Agias Olgas street,14233 N.Ionia,Athens,Greece;Hiroshi Yoshida,Associ-ate Professor,Department of Surgery,Nippon Medical School Tama Nagayama Hospital,1-7-1 Nagayama,Tama-city,Tokyo,206-8512,JapanLiu QY,Li HG,Gao M,Lin XF,Li Y,Chen JY.Primary clear cell carcinoma in the liver:CT and MRI findings.World J Gastroenterol 2011;17(7):946-952 Available from:URL:http:/ DOI:http:/dx.doi.org/10.3748/wjg.v17.i7.946Qing-Yu Liu,Hai-Gang Li,Ming Gao,Xiao-Feng Lin,Yong Li,Jian-Yu ChenBRIEF ARTICLE World J Gastroenterol 2011 February 21;17(7):946-952 ISSN 1007-9327(print)ISSN 2219-2840(online)2011 Baishideng.All rights reserved.Online Submissions:http:/ 21,2011|Volume 17|Issue 7|WJG|INTRODUCTIONHepatocellular carcinoma(HCC)is the most common primary malignant tumor of the liver.It can be classified according to its histological architecture or cytological features.HCC includes various cytological types;the less common ones are clear cell type,spindle cell type,giant cell type,small cell type and squamous cell type1,2.Prima-ry clear cell carcinoma of the liver(PCCCL)is rare,with a frequency varying between 2.2%and 6.7%among HCCs reported in the published literatures3,4.Due to the accu-mulation of glycogens and/or fats,the PCCCL cell cyto-plasm is clear to hematoxylin-eosin staining.PCCCL may pose a diagnostic dilemma even with histological evalua-tion because the morphology of PCCCL cells is similar to that of extrahepatic clear cell tumors,such as clear cell cancers of the kidneys,adrenal glands,ovaries,thyroid,en-dometrium,uterine cervix,and vagina5,6.PCCCLs should be differentiated from metastatic clear cell cancer because their treatment strategies and prognoses are quite differ-ent.The prognosis of PCCCL is generally considered bet-ter than that of the common type of HCC(CHCC)3,7,8.Computed tomography(CT)and magnetic resonance imaging(MRI)are important examinations for the de-tection and characterization of liver tumors9,10.To our knowledge,the imaging features of PCCCL have rarely been reported in the English literature11.The purpose of this study was to describe the CT and MRI findings of PCCCL and compare them to CHCC to determine whether any differences exist between the two groups.MATERIALS AND METHODSPatientsBetween January 2005 and August 2009,a total of 570 patients with primary HCC underwent hepatectomy at the Second Affiliated Hospital of Sun Yat-sen University.Twenty(3.5%)of these patients had pathologically con-firmed PCCCL.The participants of this study included 20 patients with PCCCL and 127 patients with CHCC(randomly selected from the other 550 cases of primary HCC).No patient had received preoperative treatment,such as interventional therapy or chemotherapy.Of the 20 patients with PCCCL,14 had right upper abdominal pain,two complained of fatigue and four were asymptomatic.All patients with PCCCL were positive for HBsAg,and two were positive for anti-hepatitis C virus-IgG.The serum concentration of-fetoprotein(AFP)was 5.8-68 787.0 g/L for PCCCL patients,with a median of 149.9 g/L.Of the 20 patients with PCCCL,17 were AFP-positive(25 g/L).Pathologic examinations were retrospectively reviewed by an experienced pathologist.According to diagnos-tic criteria generally accepted by pathologists in China,PCCCL was diagnosed when clear cells accounted for more than 50%of the tumor1,3,4,12.Imaging protocolsCT or MRI examinations were performed no more than 5 days before hepatectomy.Thirteen patients with PCCCL and 73 patients with CHCC underwent dynamic CT ex-amination using a spiral CT scanner(HiSpeed NX/I;GE Medical Systems,Milwaukee,WI)or a multi-detector CT scanner(Sensation 64;Siemens Medical Solutions,Erlan-gen,Germany).The scan parameters were as follows:5-7 mm slice thickness reconstructions,120-kV,220-400 mA current,25 cm field of view,and 256 256 matrix.Scans began at the dome of the diaphragm and proceeded in a caudal direction.After pre-contrast CT scans,the pa-tients underwent dynamic contrast-enhanced scans.A bo-lus injection of 80-100 mL of non-ionic contrast medium(Iopamidol,Bracco,Milano,Italy)with a concentration of 350 mg I/mL was given via the antecubital vein at a rate of 3.5 mL/s.Images of the hepatic arterial phase(HAP),portal venous phase(PVP)and equilibrium phase(EP)were obtained at 25 s,70 s and 120 s,respectively,after the injection of contrast agent.Seven patients with PCCCL and 54 patients with CHCC underwent MRI studies with a 1.5-T MR unit(Gyroscan Intera,Philips Medical System,Best,the Neth-erlands).Unenhanced MR images included T1-weighted images with a water-selective excitation technique(FFE,TR 218ms,TE 4.9 ms,flip angle of 80,one acquisition)and turbo spin-echo T2-weighted images with fat satura-tion(TR 1600 ms,TE 70 ms,TSE Factor 24,three acqui-sitions).Five patients with PCCCL and 43 patients with CHCC underwent dynamic contrast-enhanced MR scans using a high-resolution turbo spin-echo sequence(TR 5.3 ms,TE 1.4 ms,flip angle of 40,3.0-mm slice thick-ness,no gap,one acquisition)via a power injector;con-trast agent was administrated at a rate of 2.5 mL/sec.HAP,PVP and EP scans were obtained at 20,60,and 110 s,respectively.The other 13 patients(2 with PCCCL and 11 with CHCC)received manual injections of gadopentetate dimeglumine(Magnevist,Bayer Schering,Berlin,Germa-ny)at a dose of 0.1 mmol/kg;post-contrast T1-weighted images were obtained at PVP(60-80 s after injection)with the same scanning parameters as the pre-contrast T1W scan.Regardless of the technique employed,axial and coronal images were acquired with 5.0-mm slice thickness.Image interpretationThe CT and MRI images were retrospectively analyzed by two radiologists who have 10 and 15 years of experience in diagnosing abdominal diseases.Neither radiologist was aware of the patients clinicopathological data.Reviews were performed jointly and by consensus.The presence of liver cirrhosis,tumor size,the enhancement pattern on dynamic contrast scanning,the presence of pseudo-capsule,tumor rupture,portal vein thrombus,and lymph node metastasis were recorded.A typical HCC enhance-ment pattern was defined as early enhancement at HAP and rapid contrast medium washout at PVP or EP with hypo-attenuation/intense signal or iso-attenuation/intense signal9,10.Statistical analysisDifferences in mean age and tumor size were assessed Liu QY et al.Primary clear cell carcinoma in the liver947February 21,2011|Volume 17|Issue 7|WJG|with an independent-samples t test.Differences in the frequencies of liver cirrhosis,tumor capsule formation,tumor rupture,typical enhancement pattern,portal vein tumor thrombus and lymph node metastases between the two groups were compared using the Chi-squared test or Fischers exact test.A P value of 0.05 or less was consid-ered significant.Statistical analysis was performed using the SPSS 13.0 software package(SPSS Inc.,Chicago,IL,USA).RESULTSThe male-to-female ratio was 4.0:1 in the PCCCL group and 6.1:1 in the CHCC group.The mean age was 52.00 10.09 years(range,29-66 years)in the PCCCL group and 51.82 13.20 years(range,19-83 years)in the CHCC group.There were no statistical differences between the two groups regarding sex or age(P=0.733 and P=0.953,respectively).Table 1 summarizes the imaging features observed in pa-tients with PCCCL and patients with CHCC.Both PCCCL and CHCC were prone to occur in patients with liver cirrho-sis,with a rate of 80.0%and 78.7%,respectively.The mean sizes of PCCCLs and CHCCs were 7.28 4.25 cm(range,2.0-15.9 cm),and 6.96 3.98 cm(range,1.0-17.0 cm),respectively.Small HCCs with diameters 3.0 cm were found in 25.0%(5/20)of PCCCL cases and 19.7%(25/127)of CHCC cases.No statistically significant differences in mean size or ratio of small HCC were found between the two groups(P=0.658 and 0.803,respectively).Compared with CHCCs,PCCCLs were more prone to form pseudo capsules,with a rate of 49.6%and 75.0%,respectively(P=0.034).Pseudo capsules showed hypo-attenuation/intensity haloes on pre-contrast scans and rim enhancement after contrast administration(Figures 1 and 2).A higher percentage of tumor rupture was found in patients with PCCCL(15.0%,3/20)than in patients with CHCC(3.1%,4/127);however,there was no sig-nificant difference between the two groups(P 0.05).Of the 20 PCCCL cases,three showed tumor ruptures.The ruptured tumors were 15.9 cm,10.9 cm and 9.3cm in diameter and were located at the periphery of the liver with protruding contours.Two cases presented as discon-tinuities of the liver surface on CT scan(Figure 1).The remaining case presented a local hematoma at the rupture site on MRI,which appeared as mixed iso-/hypo-intense signals on T1WI and hypo-intense signals on T2WI with no enhancement after injection of contrast agent.Typical HCC enhancement patterns were noted in 72.2%(13/18)of PCCCLs and 83.6%(97/116)of CHCCs;however,no significant difference was found between the two groups(P 0.05)(Figures 1 and 3).The other five PCCCL cases showed atypical CT features on dynamic scan:two cases showed minimal enhancement and remained hypo-attenuated at HAP and PVP,while the other three cases showed gradual contrast enhancement during the portal phase.Four patients(20.0%)with PCCCL had portal vein tumor thrombosis:one located at the left branch of the portal vein,one at the right branch,and one at the right anterior branch and main portal vein.Compared with CHCC patients,PCCCL patients showed a slightly higher incidence of portal vein tumor thrombosis(17.3%and 20.0%,respectively);however,there was no significant dif-ference between the two groups(P 0.05).No PCCCL patients and 2.4%(3/127)CHCC patients showed sign of lymph node metastasis(P 0.05).DISCUSSIONPCCCL is a specific and rare subtype of primary HCC.The reported incidence of PCCCL is 0.4%-37%;inconsis-tent diagnostic criteria may be responsible for the variable reports1,3,4,7,8,12,13.Lai et al7 suggested that the diagnosis of PCCCL could be made even when the proportion of clear cells was 30%.Most studies diagnosed PCCCL when the proportion of clear cells was 50%1,3,4,12.Us-ing this criteria,PCCCL only accounts for 2.2%-6.7%of all resectable HCCs in most reports3,4.Among the 570 cases of primary HCC resected in our hospital,only 3.5%patients had PCCCL.The clear cell development is pre-sumed to involve metabolic disorders and abnormalities of sugar metabolism14,15.The clinicopathological presentations of PCCCL were different from those of CHCC.The rates of hepatitis C infection and capsule formation were higher in PCCCL patients than in those with CHCC;however,no remark-able differences in patients age,sex,AFP-positive rate or 948February 21,2011|Volume 17|Issue 7|WJG|Table 1 Characteristics of clear cell hepatocellular carcinoma in the liverParametersPCCCL(n=20)CHCC(n=127)P valueSex0.733 Male16109 Female418Liver cirrhosis1.000 Positive16100 Negative427Tumor diameter(cm)0.803 3.0525 3.015102Capsule formation0.034 Positive1563 Negative564Rupture0.053 Positive34 Negative17123Typical enhancement pattern0.399 Positive1397 Negative519Portal vein tumor thrombus1.000 Positive422 Negative16105Lymph node metastases1.000 Positive03 Negative20124PCCCL:Primary clear cell carcinoma of the liver;CHCC:Common type of hepatocellular carcinoma.Liu QY et al.Primary clear cell carcinoma in the liver949February 21,2011|Volume 17|Issue 7|WJG|DCBAEFigure 1 Primary clear cell carcinoma of the liver in a 47-year-old woman.A:On pre-contrast computed tomography scan,the mass shows slight hyper-atten-uation with a hypo-attenuation halo(arrows);B:At hepatic arterial phase,the mass shows early enhancement;C:At the equilibrium phase,the mass presents hypo-attenuation with rim enhancement(arrows);D:At portal venous phase,the reconstructed coronal image shows the mass with a discontinuous liver capsul