When should a liver mass suspected of being a hepatocellular carcinoma be biopsied?

I n medicine, the role of pathological examination has reigned supreme as the gold standard for the diagnosis of neoplasms, and sophisticated approaches and techniques have been developed to acquire tissue for pathological diagnosis. For example, percutanous fine-needle aspiration (FNA) of liver lesions is widely available to obtain a pathological diagnosis of hepatocellular carcinoma (HCC). However, concurrent with the advent of these technological advances, major advances have also been made in medical knowledge, imaging modalities, and therapeutic options that can alter the need for pathological confirmation of neoplastic disease. In this issue of Liver Transplantation and Surgery, Takamori et al1 provide data suggesting that cancer seeding is a risk of obtaining a pathological diagnosis. Based on this evidence and other information in the literature, the knowledgeable clinician must now ask, when is a liver biopsy of a liver mass indicated? The answer to this question depends on a careful assessment of the risks and potential benefits, described in the following paragraphs. What is the risk of obtaining tissue from a liver mass? The risk of a liver biopsy relates to (1) the procedure itself, (2) the consequences of the procedure, and (3) the potential mismanagement and emotional distress from interpretive errors. The risk of the procedure itself is related to pain, potential infection, and hemorrhage. Although pain is common, it is transient and well controlled by analgesics. The risk for infection is mainly theoretical because of the use of aseptic techniques, and we personally have never seen an infection resulting from an FNA of a liver mass. Hemorrhage is the most salient complication because of its morbidity and frequent need for hospitalization, blood transfusions, and occasionally surgery, and the risk for death. This risk is greater in HCC because these lesions are usually hypervascular. In one series of 159 patients with HCC who underwent FNA, 4 patients (2.5%) bled significantly; 2 patients required surgery, 1 patient died, and 1 patient responded to conservative management.2 Bleeding into the peritoneum is also associated with peritoneal seeding of the disease and therefore promotion of metastasis.3 Thus, the hemorrhagic complication rate of obtaining tissue from HCC is significant. The risk for tumor seeding from introducing a needle into the liver is even more consequential than the risk for bleeding. Tumor seeding can change a potentially treatable localized disease into metastatic disease and directly reduce the effectiveness of locoregional therapies (i.e., transplantation, surgical resection, radiofrequency ablation, cryosurgery, and ethanol ablation). Tumor seeding can be direct, as evidenced by needle-tract seeding, or indirect, with tumor dissemination into the bloodstream. Although all experienced clinicians have seen examples of needle-tract seeding, the information available is largely anecdotal. However, Takamori et al1 now provide data on the incidence of needle-tract seeding after percutanous biopsy of an HCC. In this retrospective experience, a 5.1% risk for needle-tract seeding was observed. Of even greater potential concern, Louha et al,4 using molecular techniques (reverse-transcriptase polymerase chain reaction for alphafetoprotein messenger RNA), showed that needle biopsies of HCC are associated with evidence of tumor dissemination into the circulation. Although the biological consequence of this observation is unclear and the number of patients small, the observation is disconcerting if the procedure is unnecessary (vide infra). Collectively, these observations suggest tumor dissemination is substantial and must be weighed as an established risk of the procedure. The risk for mismanagement after interpretive errors with liver biopsy specimens is also significant. FNA was a major development in the field of pathology. Usually performed under ultrasound guidance, FNA became an important diagnostic tool with at least the same accuracy for the diagnosis of focal liver lesion as the core biopsy technique.5 Bell et al6 showed that