The diagnostic reference standard was histology. In each patient, an FNB GSK458 order was concurrently performed within the nodule and the surrounding liver parenchyma. The procedure was repeated in all cases with unsolved histological diagnosis (i.e., patients showing similar histological features of cirrhosis within and outside the nodule). A 21-gauge trenchant needle for microhistology

(Biomol, HS Hospital Service, Italy) was used, and the diagnosis was made according to International Working Party criteria.10 Formalin-fixed,paraffin-embedded liver sections were examined by an experienced liver pathologist (G. R.) who was unaware of the results of the clinical and radiological examinations. All liver biopsy samples were re-evaluated by a second expert pathologist (M. R.) who was unware of the clinical, radiological, and pathological diagnoses.

The criteria for diagnosing small and well-differentiated HCCs, which include the so-called very early HCC, are well standardized.11, 12 Table 1 shows the criteria used to distinguish well-differentiated HCCs from high-grade dysplastic nodules. Tumor cell differentiation was evaluated Smoothened antagonist according to the Edmondson-Steiner grading system.13 Figure 1 shows the representative histological features of HCC grading of the series under study. Arterial hypervascularization (contrast wash-in) was a contrast hyperenhancement of the nodule (hyperechogenicity on US, hyperdensity on CT, hyperintensity on MRI) taking place during the arterial phase of the radiological examination, as compared with the surrounding liver parenchyma. Portal/venous contrast wash-out was a hypoenhanced pattern of the nodule (hypoechogenicity on US, hypodensity on CT, hypointensity on MRI) with respect to the surrounding liver parenchyma taking place during the portal/venous phase of the radiological examination. The typical radiological pattern of HCC was the presence of wash-in followed by wash-out of the contrast medium. According to the American Association for the Study of the Liver Disease guidelines, Tacrolimus (FK506) the radiological diagnosis of HCC in 1- to 2-cm HCC was the presence

of the typical radiological pattern on two dynamic imaging techniques. For >2-cm nodules, a single dynamic study showing the typical vascular pattern for HCC is required.2 CT and MRI images were blindly and independently read by two experienced radiologists (L. V. F. and P. B.) who were unaware of the liver biopsy results. MRI was performed with a 1.5-T system (Avanto; Siemens Medical Systems, Erlangen, Germany) using a phased-array torso coil for signal detection. All patients underwent transverse T1-weighted and T2-weighted MRI and multiphasic contrast-enhanced dynamic three-dimensional MRI of the whole liver with fat suppression. T1-weighted imaging included breath-hold in-phase gradient echo (175/5 TR/TE, 256 × 112 matrix, 70° flip angle) and out-of-phase gradient echo (175/2.38 TR/TE, 256 ×112 matrix, 70° flip angle).