Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor prognosis. This warrants urgent improvement in the diagnosis and treatment. Liver biopsy plays very important role in the diagnosis and prognosis of HCC, but with technical advancements and progression in the field of imaging, clinical guidelines have restricted the role of biopsy to very limited situations. Biopsy also has its own problems of needle tract seeding of tumor, small risk of complications, technical and sampling errors along with interpretative errors. Despite this, tissue analysis is often required because imaging is not always specific, limited expertise and lack of advanced imaging in many centers and limitations of imaging in the diagnosis of small, mixed and other variant forms of HCC. In addition, biopsy confirmation is often required for clinical trials of new drugs and targeted therapies. Tissue biomarkers along with certain morphological features, phenotypes and immune-phenotypes that serve as important prognostic and outcome predictors and as decisive factors for therapy decisions, add to the continuing role of histopathology. Advancements in cancer biology and development of molecular classification of HCC with clinic pathological correlation, lead to discovery of HCC phenotypic surrogates of prognostic and therapeutically significant molecular signatures. Thus tissue characteristics and morphology based correlates of molecular subtypes provide invaluable information for management and prognosis. This review thus focuses on the importance of histopathology and resurgence of role of biopsy in the diagnosis, management and prognostication of HCC.

Rare diaphragmatic tumor mimicking liver mass

Primary tumors of the diaphragm are quite rare. About 150 cases have been reported in the literature. Fibrosarcomas are the commonest malignant neoplasms of the diaphragm; however, only a few(less than 20) cases have been reported to date. We present the case of an extremely rare tumor of the diaphragm mimicking a liver mass. The patient, a young 28-year-old woman, presented with an 8-month-history of mildly progressive upper abdominal pain and early fullness after meals. Computed tomography scan of the abdomen revealed a mass located in the region of the left lobe of the liver with non visualized left lobe and partial vascular supply of the mass from the left hepatic artery. The tumor was also seen to draw its vascularity from bilateral internal mammary arteries. Surgical excision and hepatectomy was planned, keeping in mind the diagnosis of an atypical left hepatic mass. Laparotomy revealed a left diaphragmatic tumor growing caudally into the upper abdomen, compressing and splaying the liver along the left medial surface where the tumorwas virtually adherent to it. Successful excision of the mass and subsequent histopathological and immunochemistry examination of the specimen revealed low grade fibromyxoid sarcoma of the diaphragm. This case highlights the unusual presentation of a diaphragmatic mesenchymal tumor and how it can be mistaken as an atypical liver mass. It also emphasizes the tumoral vascular supply as an indicator of its organ of origin.

Ductal paucity and Warkany syndrome in a patient with congenital extrahepatic portocaval shunt

An eleven-year-old clinically dysmorphic and devel-opmentally retarded male child presenting with com-plaints of 5 episodes of recurrent cholestatic jaundice since 3 years of age was evaluated. Imaging revealed features consistent with congenital extrahepatic porto-caval shunt(Abernethy type 1b), multiple regenerative liver nodules and intrahepatic biliary radical dilatation. The presence of ductal paucity and trisomy 8 were con-firmed on liver biopsy and karyotyping. The explanation for unusual and previously unreported features in the present case has been proposed.

Bile Cast Nephropathy in Patients with Acute Kidney Injury Due to Hepatorenal Syndrome:A Postmortem Kidney Biopsy Study

Background and Aims:The role of bile cast nephropathy (BCN) in pathogenesis of hepatorenal syndrome (HRS) in decompensated cirrhosis and acute on chronic liver failure (ACLF) is unknown.This study aimed to determine the frequency of BCN detected on postmortem renal biopsy among patients with decompensated cirrhosis and ACLF who had been admitted with acute kidney injury due to HRS (HRAAKI) and expired during that hospitalization.Methods:One-hundred-twenty-seven postmortem renal biopsies with adequate size (>1 cm in length) were included for analysis.These were obtained from 84 patients with decompensated cirrhosis and 43 patients with ACLF.Results:BCN was detected in 57 of the total 127 (44.8%) renal biopsy specimens.Patients with BCN had significantly higher levels of serum total bilirubin,total leukocyte count and model for end-stage liver disease score,as compared to those without BCN.BCN was detected in 32/43 (74.4%) of the patients with ACLF,as compared to 25/84 (29.7%) of the patients with decompensated cirrhosis (p < 0.001).On multivariate analysis,direct bilirubin (OR (95% CI):1.27 (1121-1.698);p < 0.001)and presence of ACLF (OR (95% CI):2.603 (1.054-7.111);p =0.041) were found to be significant predictors of BCN on postmortem renal biopsy.Conclusion:BCN was found in 72.1% of patients with ACLF and 27.4% patients with decompensated cirrhosis who had been hospitalized with an admitting diagnosis of HRS-AKI and who expired during that hospitalization and underwent postmortem renal biopsy.Direct serum bilirubin and presence of ACLF were found to be significant predictors of BCN on postmortem renal biopsy.

Pathomolecular characterization of HCC in non-cirrhotic livers

Hepatocellular carcinoma(HCC)is the most common primary liver cancer and usually arises in cirrhotic livers.Increasingly,it is diagnosed in non-cirrhotic livers.A variety of risk factors and etiologies can trigger the development of HCC in non-fibrotic and non-cirrhotic backgrounds.The most important causes are metabolic syndrome and hepatitis B virus infection.Postulated pathogenetic mechanisms are direct carcinogenesis,chronic liver injury and repair cycles,and genetic/epigenetic aberrations.Histopathology has a very important role in the diagnosis of non-cirrhotic HCC.Gross features of non-cirrhotic HCC are quite different from HCC originating in a cirrhotic background.Microscopic characteristics are similar to a classical HCC.However,certain histological variants show a predilection to occur in non-cirrhotic livers.These encompass fibrolamellar,scirrhous,steatohepatitic and mixed hepato-cholangiocarcinoma subtypes.Due to the non-cirrhotic background,adenoma,metastasis and most of the other non-neoplastic and neoplastic conditions enter the differential diagnosis.Genomic studies and morpho-molecular classifications of HCC provide further understanding of the molecular pathogenesis of non-cirrhotic HCC.This group however,has rarely been exclusively studied.This review offers an update of etiology,patho-molecular characteristics and differential diagnosis of HCC arising in non-cirrhotic backgrounds.