In 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 FNA cytological examination combined with histological examination of visible fragments of tissue ejected from the needle had a sensitivity of 66.6% for HCC (6 of 9 specimens). In a series of 58 cases of HCC, Bru et al7 confirmed an FNA sensitivity of 69%, with 1 case of false-positive diagnosis (positive and negative predictive values of 97% and 40%, respectively). In this study, no relationship between HCC diameter and FNA positivity was shown. Aspiration of necrotic material and the degree of differentiation of the tumor seem to be limiting factors for the sensitivity of FNA. Well-differentiated HCCs are virtually impossible to differentiate from benign hepatocytes. For example, Rapaccini et al8 followed up 12 cases of focal liver lesion with an initial FNA diagnosis of a regenerating nodule. During an average follow-up of 10.2 months, HCC was subsequently diagnosed in 10 of these patients. These studies highlight the clinical axiom that a negative biopsy result is not helpful in suspected HCC. Thus, an FNA is of limited value in the management of patients with suspected HCC because a negative result is difficult to interpret and a positive biopsy result only confirms the clinical diagnosis.

What is the positive predictive value of imaging modalities? Most benign space-occupying lesions in the liver can be appropriately diagnosed by imaging modalities, patient history, physical examination, and appropriate biochemical and serological studies. Few would disagree that most simple liver cysts, cavernous hemangiomas, focal fat, and focal nodular hyperplasia can readily be diagnosed by complementary imaging modalities (e.g., computed tomography, magnetic resonance imaging, and ultrasound studies). Likewise, liver metastases are also readily diagnosed because of the history of cancer, numerous lesions within the liver, or their radiographic appearance.9 Furthermore, in the context of chronic liver disease, we now appreciate that HCC is the principle diagnostic concern. Recently, Torzilli et al10 assessed the accuracy of radiographic imaging studies, including angiography, for HCC in the absence of FNA. The sensitivity, specificity, and positive and negative predictive values as percentages were all greater than 98% in 107 patients with HCC. Although these numbers need to be confirmed, they suggest that in the right clinical context, the clinical diagnosis of HCC can be readily established, obviating the need for a histological diagnosis.

Will obtaining a liver biopsy of an HCC alter clinical outcome? This is the most difficult question to answer because published literature is not available to answer this question and likely never will be. In the past, the outcome for most patients with HCC regardless of stage was believed to be dismal. However, with the realization that transplantation for early-stage HCC results in prolonged disease-free survival (>5 years),11 most transplant physicians and/or surgeons prefer to avoid a biopsy unless it would change management. If the clinical diagnosis appears firm and a definitive and potentially curative treatment option is available, why risk hemorrhagic complications, needle-track seeding, and/or tumor vascular dissemination? In this context, a preoperative biopsy may alter outcome and, in a given patient, deny that patient the opportunity for the best therapy available. Thus, in our transplant unit, we only biopsy lesions for which the alphafetoprotein level is less than 20 ng/mL, the lesion is not hypervascular on angiography, and the presence of an HCC will favorably alter the patient's candidacy for liver transplantation. If resection appears to be the best option, we proceed to surgery without a preoperative biopsy. We realize our approach may appear aggressive, but in our transplant experience, we have never had a misdiagnosis.12

What will become the gold standard for the diagnosis of HCC in clinical studies if biopsies are to be avoided? This is a question for academic pursuits rather than one for improving patient care. Nonetheless, it becomes an important question for academic studies, and a consensus conference will be necessary to answer this question. Such a conference is now being planned by the European Association for the Study of the Liver in 2000. We await the consensus results from this conference to answer this question, but without doubt, the conference will develop nonpathological criteria for the diagnosis of HCC using clinical and radiographic information (e.g., vascularity of the lesion, presence of cirrhosis, an elevated alphafetoprotein level).

Will these suggestions become established as the standard of care for the next millennium? Predictions, especially those regarding the future, are dangerous, as Yogi Berra (an American baseball icon) once stated. Nonetheless, we believe that imaging techniques will continue to evolve, resulting in a greater sensitivity and specificity than current techniques, further limiting the utility of pathological examination. Conversely, two developments may alter our predictions. First, the information obtained from molecular analysis of malignant tissue may have such an impact on treatment and outcome that obtaining tissue will be essential. A molecular diagnosis of HCC could potentially become the gold standard. This concept is far from reality but is the goal of many investigators in the field, and with the advent of DNA chip array technology, its practical application has been accelerated. Second, chemotherapeutic agents may be developed that are so effective that their administration during a biopsy procedure would protect against tumor dissemination. However, until such developments are clinical reality, we advise against the clinical custom of performing a biopsy of a liver mass lesion as a reflex without considering the issues raised here.

This was sent to me by someone who has the time to look up reports on Liver conditions and treatment... ((((YOU KNOW WHO YOU ARE BIG HUG)))

But the fact that is stated here is one that I knew of long before I knew I had HCV... The only reason I don't let this happen to my body is I've had this condition to long to chance that I don't have HCC and I will do anything to prevent that from spreading.