BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs ...BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established.AIM To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis.METHODS A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups:A(15 cases with desmoplastic liver metastasis)and B(14 cases with replacement liver metastasis).Clinical information was obtained from patients’charts.Mismatch repair proteins,BRAFV600E,and PD-L1 were evaluated by immunohistochemistry.Five cases were selected randomly from each group for whole exome sequencing(WES)analysis.RESULTS In the primary tumor,expanding growth pattern,low tumor budding score(TBS),and Crohn’s disease-like response(CDR)were associated with desmoplastic liver metastasis and better overall survival,whereas infiltrating growth pattern alone of primary carcinoma could predict the replacement liver metastasis and worse overall survival(P<0.05).On WES analysis,primary carcinoma with desmoplastic liver metastasis showed mutations in APC(4/5);TP53(3/5);KRAS,PIK3CA,and FAT4(2/5);BRCA-1,BRCA2,BRAF,and DNAH5(1/5),whereas primary carcinoma with replacement liver metastasis showed mutations in APC and TP53(3/5);KRAS,FAT4,DNH5,SMAD,ERBB2,ERBB3,LRP1,and SDK1(1/5).CONCLUSION The HGPs,TBS,and CDR of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis,response to therapy,and patients’prognosis.展开更多
BACKGROUND Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct(IPNB),distant metastasis remains unexplained especially in cases of carcinoma in situ.In the present study,we report...BACKGROUND Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct(IPNB),distant metastasis remains unexplained especially in cases of carcinoma in situ.In the present study,we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain.CASE SUMMARY A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma.Laboratory tests on admission reported a mild elevation of alkaline phosphatase,γ-glutamyl transpeptidase,and total bilirubin in serum.Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct(CBD)extending to the left hepatic duct.Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern.Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis.Therefore,a diagnosis of IPNB cT1N0M0 was established.Left hepatectomy with bile duct reconstruction was performed.Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement.The patient was monitored carefully by regular examinations.However,at 32 mo after the operation,a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level.Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated.In addition to histopathological results,a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer.CONCLUSION This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.展开更多
基金the Human Resources Development Program for the Outstanding Talents in The Fifth People’s Hospital of Shanghai,Fudan University,No.2017WYRCJY09the Key Medical Speciality of The Fifth People’s Hospital of Shanghai,Fudan University,No.2017WY202K08
文摘BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established.AIM To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis.METHODS A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups:A(15 cases with desmoplastic liver metastasis)and B(14 cases with replacement liver metastasis).Clinical information was obtained from patients’charts.Mismatch repair proteins,BRAFV600E,and PD-L1 were evaluated by immunohistochemistry.Five cases were selected randomly from each group for whole exome sequencing(WES)analysis.RESULTS In the primary tumor,expanding growth pattern,low tumor budding score(TBS),and Crohn’s disease-like response(CDR)were associated with desmoplastic liver metastasis and better overall survival,whereas infiltrating growth pattern alone of primary carcinoma could predict the replacement liver metastasis and worse overall survival(P<0.05).On WES analysis,primary carcinoma with desmoplastic liver metastasis showed mutations in APC(4/5);TP53(3/5);KRAS,PIK3CA,and FAT4(2/5);BRCA-1,BRCA2,BRAF,and DNAH5(1/5),whereas primary carcinoma with replacement liver metastasis showed mutations in APC and TP53(3/5);KRAS,FAT4,DNH5,SMAD,ERBB2,ERBB3,LRP1,and SDK1(1/5).CONCLUSION The HGPs,TBS,and CDR of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis,response to therapy,and patients’prognosis.
文摘BACKGROUND Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct(IPNB),distant metastasis remains unexplained especially in cases of carcinoma in situ.In the present study,we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain.CASE SUMMARY A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma.Laboratory tests on admission reported a mild elevation of alkaline phosphatase,γ-glutamyl transpeptidase,and total bilirubin in serum.Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct(CBD)extending to the left hepatic duct.Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern.Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis.Therefore,a diagnosis of IPNB cT1N0M0 was established.Left hepatectomy with bile duct reconstruction was performed.Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement.The patient was monitored carefully by regular examinations.However,at 32 mo after the operation,a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level.Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated.In addition to histopathological results,a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer.CONCLUSION This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.
