Discussion
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with an estimated incidence of about 1,000,000 cases per year worldwide. This tumor represents the seventh most common cancer in men and the ninth most common cancer in women. HCC shows considerable differences among the various geographic areas with respect to incidence, etiology, and clinico-pathologic features. In Western countries, as well as in Japan, HCC emerge in cirrhotic livers in more than 90% of cases and yearly incidence of HCC in cirrhotic patients may reach 3-5%. HCC is thought to develop through two main pathways: a de novo carcinogenesis and a multistep progression. The multistep progression includes the transition from frankly benign nodules (large regenerative nodules or macroregenerative nodules) to equivocal lesions (dysplastic nodules or borderline lesions), to early HCC (very well differentiated tumor of Edmondson grade 1), and, finally, to overt HCC (advanced tumor of Edmondson grade 2 or greater). Along with progression from regeneration to cancer, the intranodular portal blood supply tends to decrease and, in contrast, the intranodular arterial supply tends to increase in the path from benign to malignancy. Morphologically, HCC may be divided nodular type, infiltrative type, and diffuse type. The infiltrative type HCC strands into surrounding tissue, and frequently invade vascular structures, particularly portal vein branches.
Extrahepatic metastasis occurs at a relatively late stage in HCC. The reported incidence of extrahepatic metastasis ranges from around 50% to 70% in Western countries. The incidence of extrahepatic metastasis tends to be slightly higher in HCC without cirrhosis than HCC with cirrhosis. In general, hematogeneous metastases are more common than lymphatic ones in HCC. Hematogeneous metastases are noted in lung (47,6%), adrenal glands (8,3%), bone (5,6%), gastrointestinal tract (4,7%), gall bladder (3,5%) and pancreas (3,0%). Recent studies have shown that it is possible to detect circulating malignant cells even at early stages of the disease, whose ultimate development into clinically recognizable metastases depends on several additional parameters, such as immunologic factors and attachment-invasion capability of these cells. In addition to these cellular mechanisms, the patients should survive long enugh to allow the microscopic nests to be clinically relevant and/or detectable by imaging techniques. As expected, the rate of dissemination runs parallel to the stage of the tumor, but in a minority of patients the symptoms due to the metastatic spread may be the first symptom of the disease.
Pain is the main symptom of bone disease, with or without motor disturbance, and the most of the cases begins with pathologic fractures.
Contrast-enhanced spiral CT of HCC lesions defines the extent and location of intrahepatic disease, involvement of surgically critical areas (portal hepatis, inferior vena cava, major bile ducts), and presence of extrahepatic disease.
The bone metastases are demonstrated by radiography, CT, and nuclear scintigraphy, in patient with skeletal pain. Purely osteolytic lesions, without surrounding sclerosis, are seen on radiograms in every case; rupture of the cortex and spread to adjacent soft tissues are common findings. CT scans demonstrats the destructive nature of these lesions, which are associated with hypervascular bulky soft-tissue masses. Metastases exhibit increased radiotracer (99m Tc-MDP) uptake at bone scintigraphy.
To determine the characteristics of these metastases, the diagnosis is established either on the basis of concomitant occurrence of malignant bone lesions and HCC in the absence of other detectable malignant disease or on the basis of histological evidence of bone metastasis from an HCC.
