Methods of diagnosis in<unk>  have evolved with the improvement in medical imaging. The evaluation of both asymptomatic patients and those with symptoms of liver disease involves blood testing and imaging evaluation. Although historically a biopsy of the tumor was required to prove the diagnosis, imaging (especially MRI) findings may be conclusive enough to obviate histopathologic confirmation. Screening<unk>  remains associated with a high mortality rate, in part related to initial diagnosis commonly at an advanced stage of disease. As with other cancers, outcomes are significantly improved if treatment is initiated earlier in the disease process. Because the vast majority of<unk>  occurs in people with certain chronic liver diseases, especially those with cirrhosis, liver screening is commonly advocated in this population. Specific screening guidelines continue to evolve over time as evidence of its clinical impact becomes available. In the United States, the most commonly observed guidelines are those published by the American Association for the Study of Liver Diseases, which recommends screening people with cirrhosis with ultrasound every 6 months, with or without measurement of blood levels of tumor marker alpha-fetoprotein (AFP). Elevated levels of AFP are associated with active<unk>  disease, although inconsistently reliable. At levels >20 sensitivity is 41–65% and specificity is 80–94%. However, at levels >200 sensitivity is 31, specificity is 99%. On ultrasound,<unk>  often appears as a small hypoechoic lesion with poorly defined margins and coarse, irregular internal echoes. When the tumor grows, it can sometimes appear heterogeneous with fibrosis, fatty change, and calcifications. This heterogeneity can look similar to cirrhosis and the surrounding liver parenchyma. A systematic review found that the sensitivity was 60% (95% CI 44–76%) and specificity was 97% (95% CI 95–98%) compared with pathologic examination of an explanted or resected liver as the reference standard. The sensitivity increases to 79% with AFP correlation. Controversy remains as to the most effective screening protocols. For example, while some data support decreased mortality related to screening in people with hepatitis B infection, the AASLD notes. “there are no randomized trials for screening in Western populations with cirrhosis secondary to chronic hepatitis C or fatty liver disease, and thus there is some controversy surrounding whether surveillance truly leads to a reduction in mortality in this population of patients with cirrhosis.” Higher risk people In a person where a higher suspicion of<unk>  exists, such as a person with symptoms or abnormal blood tests (i.e. alpha-fetoprotein and des-gamma carboxyprothrombin levels), evaluation requires imaging of the liver by CT or MRI scans. Optimally, these scans are performed with intravenous contrast in multiple phases of hepatic perfusion to improve detection and accurate classification of any liver lesions by the interpreting radiologist. Due to the characteristic blood flow pattern of<unk>  tumors, a specific perfusion pattern of any detected liver lesion may conclusively detect an<unk>  tumor. Alternatively, the scan may detect an indeterminate lesion and further evaluation may be performed by obtaining a physical sample of the lesion. Imaging Triphasic contrast CT of<unk> . Ultrasound, CT scan, and MRI may be used to evaluate the liver for<unk> . On CT and MRI,<unk>  can have three distinct patterns of growth: * A single large tumor * Multiple tumors * Poorly defined tumor with an infiltrative growth pattern A systematic review of CT diagnosis found that the sensitivity was 68% (95% CI 55–80%) and specificity was 93% (95% CI 89–96%) compared with pathologic examination of an explanted or resected liver as the reference standard. With triple-phase helical CT, the sensitivity was 90% or higher, but these data have not been confirmed with autopsy studies. However, MRI has the advantage of delivering high-resolution images of the liver without ionizing radiation.<unk>  appears as a high-intensity pattern on T2-weighted images and a low-intensity pattern on T1-weighted images. The advantage of MRI is that it has improved sensitivity and specificity when compared to ultrasound and CT in cirrhotic patients with whom it can be difficult to differentiate<unk>  from regenerative nodules. A systematic review found that the sensitivity was 81% (95% CI 70–91%) and specificity was 85% (95% CI 77–93%) compared with pathologic examination of an explanted or resected liver as the reference standard. The sensitivity is further increased if gadolinium contrast-enhanced and diffusion-weighted imaging are combined. MRI is more sensitive and specific than CT. Liver image reporting and data system (LI-RADS) is a classification system for the reporting of liver lesions detected on CT and MRI. Radiologists use this standardized system to report on suspicious lesions and to provide an estimated likelihood of malignancy. Categories range from LI-RADS (LR) 1 to 5, in order of concern for cancer. A biopsy is not needed to confirm the diagnosis of<unk>  if certain imaging criteria are met. Pathology Micrograph of<unk> . Liver biopsy. Trichrome stain. Macroscopically, liver cancer appears as a nodular or infiltrative tumor. The nodular type may be solitary (large mass) or multiple (when developed as a complication of cirrhosis). Tumor nodules are round to oval, gray or green (if the tumor produces bile), well circumscribed but not encapsulated. The diffuse type is poorly circumscribed and infiltrates the portal veins, or the hepatic veins (rarely). Microscopically, the four architectural and cytological types (patterns) of<unk>  are: fibrolamellar, pseudoglandular (adenoid), pleomorphic (giant cell), and clear cell. In well-differentiated forms, tumor cells resemble hepatocytes, form trabeculae, cords, and nests, and may contain bile pigment in the cytoplasm. In poorly differentiated forms, malignant epithelial cells are discohesive, pleomorphic, anaplastic, and giant. The tumor has a scant stroma and central necrosis because of the poor vascularization. A fifth form – lymphoepithelioma like<unk>  – has also been described. File:Histopathology of well-differentiated<unk> .Well-differentiated<unk>  File:Histopathology of moderately differentiated<unk> .Moderately differentiated<unk> . File:Histopathology of poorly differentiated<unk> .Poorly differentiated<unk>  Staging BCLC Staging System The prognosis of<unk>  is affected by the staging of the tumor and the liver's function due to the effects of liver cirrhosis. A number of staging classifications for<unk>  are available; however, due to the unique nature of the carcinoma to fully encompass all the features that affect the categorization of the<unk> , a classification system should incorporate tumor size and number, presence of vascular invasion and extrahepatic spread, liver function (levels of serum bilirubin and albumin, presence of ascites, and portal hypertension) and general health status of the patient (defined by the ECOG classification and the presence of symptoms). Of all the staging classification systems available the Barcelona Clinic Liver Cancer staging classification encompasses all of the above characteristics. This staging classification can be used to select people for treatment. + Barcelona Clinic Liver Cancer classification Stage Description Child-Pugh class ECOG performance status 0 (very early stage) Single nodule, < 3 cm A 0 A (early stage) 1–3 nodule, all < 3 cm A or B B (intermediate stage) Multi-nodular tumor C (advanced stage) Portal invasion and extra-hepatic spread 1 or 2 D (terminal stage) Severe liver damage C 3 or 4 Important features that guide treatment include: * size * spread (stage) * involvement of liver vessels * presence of a tumor capsule * presence of extrahepatic metastases * presence of daughter nodules * vascularity of the tumor MRI is the best imaging method to detect the presence of a tumor capsule. The most common sites of metastasis are the lung, abdominal lymph nodes, and bone.
Hepatocellular carcinoma
Hepatoid tumor
Focal fatty liver
Cholangiocarcinoma
Hepatoblastoma
Echinococcosis
Liver angiosarcoma
Metastatic carcinoma