Multidisciplinary perspective of hepatocellular carcinoma: A Pacific Northwest experience

Abstract

Hepatocellular carcinoma (HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would: (1) greatly facilitate the identification of patients at risk; (2) prompt efforts to decrease risk factors; and (3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC, this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, non-invasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics.

Keywords: Diagnostic imaging; Diagnostic pathology; Epigenetic alterations; Genetic alterations; Hepatocellular carcinoma; Liver resection; Liver transplantation; Locoregional therapy; Sorafenib; Surgical modality.

Figure 1

Pathology of classical hepatocellular carcinoma. A: Gross photo of a well circumscribed, soft, yellowish to tan, and lobulated hepatocellular carcinoma (HCC) in a background of non-cirrhotic liver; B: Gross photo of a yellow and greenish, soft and lobulated HCC in a background of cirrhotic liver; C: Microphotos of HCC showing the pseudoacinar and pseudoglandular patterns, some containg the yellowish bile within the pseudoglandular structure with increased nuclear sizes; D: Microphotos of HCC showing thickened trabeculi, with increased unpaired arteries. Notice there are no normal structures present, i.e., portal tracts.

Figure 2

Pathology of fibrolamellar carcinoma. A: Microphotos of fibrolamellar carcinoma showing the thick lamellar bands of fibrosis under low power magnification; B: In higher power magnification, the tumor cells are large and polygonal with abundant eosinophilic and granular cytoplasm, large vesiculated nuclei, and prominent nucleoli.

Figure 3

A 68-year-old male with cirrhosis and surgically proven hepatocellular carcinoma. A: Thirty-four seconds after intravenous injection of ultrasound contrast (microbubbles) there is tumor (T with dashed line) enhancement; B: One and half minutes after injection the tumor (T with dashed line) is washing out of contrast. The images on the right side are a conventional sonogram (non-contrasted) of the lesion. The image on the left is a pulse inversion harmonics ultrasound for better visualization of ultrasound contrast media.

Figure 4

Ultrasound of hepatocellular carcinoma. A: Ultrasound of the liver demonstrates a heterogeneous tumor (T) in the right lobe of the liver that was later characterized as definite hepatocellular carcinoma by computed tomography; B: Same lesion (T) using color Doppler ultrasound images to demonstrate blood flow in the adjacent vessels.

Figure 5

Computed tomography of hepatocellular carcinoma in 48-year-old male with hepatitis C. A: Arterial phase contrast enhanced CT of the liver shows a strongly enhancing mass (arrow) in the right lobe, adjacent to the IVC. B: The same lesion (arrow) washes-out of contrast on the delayed phase and shows a thin capsule, this is diagnostic for HCC and corresponds to LI-RADS category 5. HCC: Hepatocellular carcinoma; CT: Computed tomography; LI-RADS: Liver imaging reporting and data system; IVC: Inferior vena cava.

Figure 6

Portal vein invasion by hepatocellular carcinoma. Computed tomography in portal venous phase shows a right lobe mass (T) and lack of enhancement of the portal vein (outlined), consistent with tumor invasion.

Figure 7

Magnetic resonance imaging of hepatocellular carcinoma in 19-year-old female. Post contrast liver magnetic resonance imaging in portal venous phase shows a large mass (arrows) arising from the left lobe of a liver without cirrhosis. This lesion that has some imaging similarities with focal nodular hyperplasia, corresponded to fibrolamellar carcinoma on pathologic analysis.

Figure 8

Radiofrequency ablation of a focal hepatocellular carcinoma. A: Contrast-enhanced MR of a 60-year-old male with cirrhosis demonstrates a single hepatocellular carcinoma in the right hepatic lobe (arrow); B: Ultrasound demonstrates a radiofrequency probe coursing through the hypoechoic tumor; C: Contrast-enhanced MR 1 mo after radio-frequency ablation demonstrates a large ablation defect, without any residual enhancement to suggest viable tumor. MR: Magnetic resonance.

Figure 9

Yttrium-90 radioembolization of diffuse, infiltrative hepatocellular carcinoma with vascular invasion. A: Contrast-enhanced MR of a 55-year-old female with cirrhosis demonstrates an infiltrative hepatocellular carcinoma replacing the anterior right hepatic lobe. Tumor-associated portal venous thrombus is present in the right portal vein (arrow); B: Digital subtraction angiogram with a microcatheter in the right hepatic artery shows diffuse tumor hypervascularity. The patient underwent a right hepatic artery Y90 radioembolization; C: Contrast-enhanced MR 12 mo after radioembolization demonstrates complete necrosis of the entire tumor with marked reduction in size. MR: Magnetic resonance; Y90: Yttrium-90.