Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials

Nodular hepatocellular carcinoma (HCC) is characterized by the presence of a pseudocapsule (constructed usually from connective fibrous tissue) that appears hypointense on T1- and T2-weighted spin-echo (SE) and gradient-echo (GE) MR imaging sequences without a contrast medium. The presence of vascular structures inside the tumor, which are verified by histological exam, affects enhancement of the PC after administrating the contrast medium: The impregnation is more evident in the dynamic study but also persists on the delayed T1-weighted SE images. The accuracy of MR in detecting the pseudocapsule of HCC and contrast enhancement of the pseudocapsule during dynamic studies were evaluated and related to pathological findings. Thirty-seven HCC were examined in 33 patients and afterwards resected. In capsulated nodules, besides usual hematoxylin, eosin, and trichrome stainings, histochemical and immunohistochemical methods were performed. On a 1.5-T MR unit, T1- and T2-weighted SE and GE FLASH 2D sequences after intravenous injection of Gd-DTPA (dynamic study) were used. In a later phase, T1-weighted SE sequences were repeated. Histologically, the pseudocapsule (thickness 0.2-6 mm) was present in 26 of 37 nodules (70%). The dynamic study was the most suitable technique to show the pseudocapsule, which was recognized in 80.7% (21 of 26 nodules). In 5 of 26 cases, the pseudocapsule, not demonstrated by MR, was thinner than 0.4 mm. In 16 of 21 cases, in the early portal phase (30-60 s), the pseudocapsule had an early enhancement, which was more evident later; in 5 of 21 cases the enhancement was observed only in the late portal phase (1-2 min). At histological examination, 14 of 16 pseudocapsules with early enhancement showed a more prominent vasculature than those with enhancement in the equilibrium phase. Magnetic resonance was a reliable tool in demonstrating the pseudocapsule of HCC. The histological examination demonstrated a good correlation between the enhancement behavior and the vessel number of the pseudocapsule.