Fibrolamellar hepatocellular carcinoma(FLC)is a rare but aggressive liver cancer of children that occurs predominantly in teenagers without a history of liver disease.Surgical resection remains the only therapeutic op...Fibrolamellar hepatocellular carcinoma(FLC)is a rare but aggressive liver cancer of children that occurs predominantly in teenagers without a history of liver disease.Surgical resection remains the only therapeutic option,and the recurrence rate is extremely high(>50%within 3 years).A newly discovered chromosomal deletion that occurs in the majority of FLCs generates a novel kinase fusion between DnaJ heat shock protein family member B1(DNAJB1)and protein kinase cAMP-activated catalytic subunit alpha(PRKACA)(DNAJB1-PRKACA).Despite its high penetrance and apparent specificity for FLC,the oncogenic role of this fusion event remains unclear.In this review article,we discuss the histology,presentation and diagnosis,current treatment,and roles of the DNAJB1-PRKACA as well as research models contributing to our understanding of this disease.展开更多
Subtypes of hepatocellular carcinoma are important for 2 primary reasons:they help improve diagnostic accuracy,as different subtypes have their own diagnostic pitfalls;they are an important building block to the perso...Subtypes of hepatocellular carcinoma are important for 2 primary reasons:they help improve diagnostic accuracy,as different subtypes have their own diagnostic pitfalls;they are an important building block to the personalization of patient care,as subtypes are enriched for shared genetic changes and biological associations.The most common subtype of hepatocellular carcinoma is steatohepatitic hepatocellular carcinoma(SH-HCC),a subtype that is strongly linked to tumorigenesis in the setting of the metabolic syndrome and metabolic-associated liver disease(MAFLD)and/or alcoholic hepatitis.SH-HCC shows macrovesicular steatosis,balloon cells,Mallory hyaline,intratumoral inflammation,and intratumoral fibrosis.This review examines the historical development of this subtype and explores in detail the histological features that are used to define SH-HCC.The strongest molecular correlates to-date include a low frequency of CTNNB1 mutations and possible activation of the IL6/JAK/STAT pathway.In addition,critical unresolved questions are discussed in detail to refine the histological definition of SHHCC,including the minimal histological thresholds needed to make the diagnosis,as well as whether or not SHHCC currently is a mixed category of tumors,containing some tumors where the distinctive morphology is driven by tumor-specific genetic changes,and other tumors where the findings are an epiphenomenon,a reflection of metabolic or alcohol-associated fatty liver disease,and not necessarily of genetic/epigenetic changes.展开更多
文摘Fibrolamellar hepatocellular carcinoma(FLC)is a rare but aggressive liver cancer of children that occurs predominantly in teenagers without a history of liver disease.Surgical resection remains the only therapeutic option,and the recurrence rate is extremely high(>50%within 3 years).A newly discovered chromosomal deletion that occurs in the majority of FLCs generates a novel kinase fusion between DnaJ heat shock protein family member B1(DNAJB1)and protein kinase cAMP-activated catalytic subunit alpha(PRKACA)(DNAJB1-PRKACA).Despite its high penetrance and apparent specificity for FLC,the oncogenic role of this fusion event remains unclear.In this review article,we discuss the histology,presentation and diagnosis,current treatment,and roles of the DNAJB1-PRKACA as well as research models contributing to our understanding of this disease.
文摘Subtypes of hepatocellular carcinoma are important for 2 primary reasons:they help improve diagnostic accuracy,as different subtypes have their own diagnostic pitfalls;they are an important building block to the personalization of patient care,as subtypes are enriched for shared genetic changes and biological associations.The most common subtype of hepatocellular carcinoma is steatohepatitic hepatocellular carcinoma(SH-HCC),a subtype that is strongly linked to tumorigenesis in the setting of the metabolic syndrome and metabolic-associated liver disease(MAFLD)and/or alcoholic hepatitis.SH-HCC shows macrovesicular steatosis,balloon cells,Mallory hyaline,intratumoral inflammation,and intratumoral fibrosis.This review examines the historical development of this subtype and explores in detail the histological features that are used to define SH-HCC.The strongest molecular correlates to-date include a low frequency of CTNNB1 mutations and possible activation of the IL6/JAK/STAT pathway.In addition,critical unresolved questions are discussed in detail to refine the histological definition of SHHCC,including the minimal histological thresholds needed to make the diagnosis,as well as whether or not SHHCC currently is a mixed category of tumors,containing some tumors where the distinctive morphology is driven by tumor-specific genetic changes,and other tumors where the findings are an epiphenomenon,a reflection of metabolic or alcohol-associated fatty liver disease,and not necessarily of genetic/epigenetic changes.
