Forner et al.1 seem determined to “unequivocally validate the value” of the criteria for noninvasive diagnosis of hepatocellular carcinoma (HCC) published by the American Association for the Study of Liver Diseases,2 that is, that nodules ≤ 20 mm in diameter in cirrhotic livers be treated as HCC without a positive biopsy if two coincidental dynamic imaging studies reveal arterial-phase hypervascularity followed by washout in the portal/venous phases; otherwise, biopsy is indicated. Unfortunately, their study methods are poorly described, and their interpretation of their (and others') findings seems blatantly forced.
A few examples: they declare that fine-needle biopsy (FNB) results were “the gold standard” used to analyze the accuracy of their imaging (contrast-enhanced ultrasonography [CEUS] plus magnetic resonance imaging [MRI]) diagnoses. Instead, the definitive diagnoses were based on variable combinations of imaging findings, clinical follow-up, and in most, but not all, cases FNB. Five nodules were never biopsied because there was already a “confident imaging diagnosis” (wasn't this diagnosis the object of their analysis?). And one nodule was definitively diagnosed as HCC based on two negative FNBs, “conclusive” findings in computed tomography and MRI (no mention of CEUS findings), “significant growth” (no specifics supplied), and recurrence 9 months after ablation. How they excluded the possibility that this nodule was a cholangiocarcinoma, a lymphoma, or a hypervascular metastatic lesion remains unexplained.
Imaging diagnosis of HCC is needed, the authors insist, because of the limitations of FNB, but their own experience belies the importance of these limitations. FNB is not feasible in certain cases (due to tumor location, coagulation disorders, ascites), but it was possible in at least 94% (84 of 89) of the small nodules they studied (the phrase “at least” seems mandatory because, as noted above, their decision to omit FNB sometimes appears to be dictated by choice rather than necessity). As for the risks of FNB-induced bleeding or tumor seeding, Forner et al. subjected their own 89 study patients to as many as three FNBs, some with multiple punctures, and not one case of bleeding or seeding is reported (actually, the question of complications is not considered at all with respect to the FNBs they performed). As for the sensitivity of FNB, their first biopsy failed to identify 30% of the true HCCs. This is something of a limitation. But if FNB misses one of three HCCs, the solution they propose (diagnosis by coincidental CEUS and MRI positivity) misses two of three of these tumors!
In our multicenter study of almost 300 nodules < 20 mm in diameter, we achieved a false negative rate of approximately 12%3 (the affirmation by Forner et al. that our findings should be regarded with caution because “no false negatives were observed” is a deliberate distortion of the facts). The success of our FNBs is due in part to the fact that we routinely collect both cytological and histological specimens (often with a single puncture). Histological analysis is especially important for small nodules, in which the distinction between a dysplastic nodule and well-differentiated HCC requires assessment of preserved tissue architecture.4 Forner et al. limited almost half of their FNB analyses to aspirates for cytology.
But even so, after the initial sampling, their repeat FNBs of the original false negatives allowed them to achieve a false-negative rate similar to ours (approximately 12%), thus validating our conviction that FNB—not imaging—is the most effective first-line approach to the diagnosis of nodules ≤ 20 mm in cirrhotic livers.