This gross liver shows numerous pale nodules of metastatic cancer.

It is not possible here to say from which organ these secondary growths came. |<img src=/f/livercancer.png>|

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IMDEPSAASIAC: Identify: This gross liver shows numerous pale nodules of metastatic cancer. It is not possible here to say from which organ these secondary growths came. Morphology: -Nodules: Massive Single focus or variable sized-multifoci, or diffuse (entire liver). -Hepatocytes arranged in cords or nests around the masses/densities. -Bile may be found in cytoplasm and in pseudocanalicula between cells. Disease: Hepatic carcinoma. Etiology (main): **Repeated cell damage in liver** Alcohol, Hep B virus, Hep C Virus, Hemochromatosis, Aflatoxin (hepatocarcinogen from plants). Or metastasis from other organs: stomach, intestine, colon, etc. Primary tumors are associated with repeated cell death and regeneration which leads to pathogenesis. Pathogenic mechanism: **KEY: REPEATED Cell death and regeneration with carcinogens=Carcinoma of liver.** Repated cell death-->HCC. Accumulations of mutations during continuous cycles of cell division may transform some hepatocytes. HBV DNA causes genomic instability--> deletions, translocations, duplications. X-proteins (from HBV) disrupts normal growth control-->activation of proto-oncogenes and disruption of cell cycles control. Also antiaptotic. HBV proteins also bind and inactivate tumor suppressor gene TP53.

Structural changes (specific, gross, and micro): **KEY: NODULES, Nest+Cords.** Primary liver carcinomas (which are almost all HCC) may appear as (1) a unifocal, massive tumor; (2) a multifocal malignancy, made of widely dstributed nodules of variable size; or (3) a diffusely infiltrative cancer, permeating widely and sometimes involving the entire liver. Sometimes snake-like masses may invade the portal vein, vena cava, and eventually the right heart.

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Extra:Histology is quite variable, ranging from well-differentiated lesions (arranged in cords or small nests) to poorly differentiated lesions, often made up of large multinucleate anaplastic giant cells. The fibrolamellar subtype (associated with young adults:20-40 yrs) is associated with a better prognosis for survival, possibly because it is not associated with cirrhosis and is more likely to be resectable. For this type, histologically, is composed of well-differentiaed polygonal cells arranged in nests or cords, separated by parallel lamellae of dense collagen bundles. The presence of intracellular bile or staining for AFP may be helpful in distinguishing HCC from other hepatic malignancies (eg, cholangiocarcinoma). |<img src=/f/livernest.png>| Are there any other sites of involvement in the body? Metastases may develop in the lung, portal vein, periportal nodes, bones, or brain Are there any other diseases where similar changes can be seen? Signs / Symptoms: Jaundice, ascites, hepatomegaly, alcoholic stigmata, asterixis, pedal edema, periumbilical collateral veins, enlarged hemorrhoidal veins, variceal bleeding, cachexia, right upper quandrant pain (uncommon).

Investigations (confirmation / gauge extent): **KEY: Raised AFP (sensitive, but not specific).** Expect total bilirubin, aspartate aminotransferase (AST), alkaline phosphatase, albumin, and prothrombin time to show results consistent with cirrhosis. Alpha-fetoprotein (AFP) is elevated in 75% of cases. Biopsy, imaging. Are there any other diseases you have studied where such tests can be positive? Increased AFP is associated with 90% of patients with HCC, but it has low specificity, because modestly elevated levels are also encountered in cirrhosis, massive liver necrosis, chronic hepatitis, normal pregnancy, fetal distress or death, fetal neural tube defects (anencephaly, spina bifida), and gonadal germ cell tumors. Very high levels are found almost exclusively in HCC. Course of disease progress (complications, monitoring, outcome): Overall prognosis for survival depends on the extent of cirrhosis and tumor stage, which then determine the appropriate treatment. HCC tends to remail confied to the liver until late in the course, when it may spread to lymph nodes, lungs, bones, adrenal glands, and other sites. Patients able to undergo a curative resection have a median survival of as long as 4 years; patients who present when they are too ill to be treated have a median survival of 3 months. Extra: A primary malignancy of the hepatocyte that generally leads to death within 6 months of onset. HCC frequently arises in the setting of cirrhosis, appearing 20-50 years following initial insult to the liver. However, 25% of patients have no history or risk factors for the development of cirrhosis. The extent of hepatic dysfunction limits treatment options, and patients usually die of liver failure. Highlight 3 important points: 1. Median survival is 7 months 2. Death from: profound cachexia, GI or esophageal bleeding, liver failure with hepatic coma, tumor rupture with fatal hemorrhage. 3. Only hope for cure is surgical resection of smaller tumors. But still have a recurrence rate of greater than 60% at 5 years. 4. Control: Vaccine against HBV. 5. Pronounced male preponderance of HCC worldwide (3:1 to 8:1). Blacks>whites. Vignette: 50 year old alcoholic male showed up to the ER complaining of unexplained weight loss, weakness, enlarged liver, and a slight pain on his right upper quadrant. Later that night, he woke up and threw up a lot of blood and died within minutes. Questions: 1. How do you distinguish primary liver cancer from metastasis in a gross specimen? Primary liver cancer presents as a unifocal nodule, whereas metastasis presents as multiple nodules.

2. What are the common sites of metastasis for cancers? What is the most important factor that determines the site for metastasis? The lungs and liver are common predilection sites for metastases; they are the circulatory sieves which have a tendency to accumulate neoplastic cells. 3. Which are the likely primary sites to produce metastasis in liver? Any area which drains into the hepatic portal system is a likely primary site: the stomach, intestines, colon, bones, etc 3. What is alpha fetoprotein? Alpha fetoprotein is a fetal antigen (i.e. expressed by embryonic tissue) and is a type of tumor marker. Alpha fetoprotein is elevated in cancer, and although it is not diagnostic, it can be useful in establishing a baseline of comparison for subsequent treatment modalities. Elevated levels are associated with hepatocellular carcinoma or embryonic cell carcinoma.