Liver biopsy interpretation in liver cancer
Authors: Charles Balabaud
Journal: Hepatology (2011)

Having the privilege of working closely with a liver pathologist, I fully agree with the comments of Brunt and Gores.1 Today, the widespread ignorance of both the medical and scientific communities about the role of liver pathologists has led to a misapprehension of the complexity of the pathology underlying hepatocellular carcinoma (HCC). There is a paradox in most specialized (tertiary) liver centers. Radiologists often perform liver biopsy to prove that imaging approaches can effectively replace this invasive procedure for diagnosing HCC; however, clinicians seldom use biopsies for what they can bring to the understanding of the disease. As a result of this paradigm shift, the time is long gone when pathologists were the most influential in the understanding of diseases. I do not, however, share the pessimism of Brunt and Gores.1 Indeed, having the chance to work with a molecular biologist and a liver pathologist, I know that pathologists have also made great progress from their interactions with molecular biologists in the understanding of what they are used to seeing (but not necessarily understanding). This is clearly illustrated by recent studies of hepatocellular adenoma (HCA) from our group. HCA is a benign hepatocellular tumor with the potential to transform into HCC. Until 2007, HCA was described as a single benign liver tumor entity in all the textbooks. Although HCA phenotypes present clear characteristics that could have led to a phenotypic classification of these tumors, it was only around 2006 that molecular biology–based approaches demonstrated HCA to be an heterogeneous entity with three major classes driven by genetic mutations (i.e., hepatocyte nuclear factor 1α, β-catenin, and inflammation).2, 3 The reason that liver pathologists ignored these phenotypes for more than 30 years is probably that they did not think that HCA could be due to genetic disorders. A similar example has been observed with the diagnostic correction brought by molecular biology approaches in cases of inflammatory HCA wrongly diagnosed as telangiectatic focal nodular hyperplasia.4 Pathologists definitely have learned from molecular biologists and will learn more from them. I doubt, however, that molecular biologists alone, without a pathological background in HCC, will be able to identify relevant subgroups of HCC in terms of diagnosis, prognosis, and/or clinical management. However, I have no doubt that liver pathologists, once they have examined the liver tissue provided to molecular biologists and have efficiently collaborated with them, will be able in the near future to identify relevant HCC subtypes. HCC is too complex an entity to be left in the hands of a single group of liver specialists, whoever they might be. The multidisciplinary approach to tackling HCC pathology in terms of diagnosis, prognosis, and clinical management should become real. In that context, liver pathologists not only should be adding tags to samples but also should be actively participating in the characterization of the samples. In the mean time, liver pathologists should keep faith in what they do best: preserving tissue for molecular studies and establishing up-to-date and meaningful pathology reports. Charles Balabaud M.D.*, * Université Bordeaux 2, Bordeaux, France.