Specific types of cirrhosis

Post-necrotic cirrhosis is characterized by large and irregular nodules with broad bands of connective tissue and occurring most commonly after viral hepatitis.

Biliary cirrhosis is defined as a chronic disorder characterized by clinical, biochemical and morphological features of long-continued cholestasis of extrahepatic or intrahepatic origin. There are primary and secondary biliary cirrhosis. In primary one the destructive process of unknown etiology affects intrahepatic bile ducts. Secondary cirrhosis resulting from prolonged mechanical obstruction of the extrahepatic biliary passages.

Indian childhood cirrhosis is an unusual form of cirrhosis seen in children at the age of 6 months and 3 years. The disease has some familial incidence

suggesting a possible genetic or common environmental origin. Death occurs due to hepatic failure within a year of diagnosis. There are 5 histologic types of ICC. The type 2 is the most common. It is characterized by ballooning degeneration of hepatocytes, with some liver cells showing Mallory bodies and surrounded by neutrophilic exudate. As a rule micronodular cirrhosis develops.

Cardiac cirrhosis is uncommon complication of severe right-sided congestive heart failure of longstanding duration. The common causes culminating in cardiac cirrhosis are cor pulmonale, tricuspid insufficiency or constrictive pericarditis. Microscopically, the hepatic sinusoids are dilated and congested with hemorrhagic necrosis of centrolobular hepatocytes. Then fibrous strands radiating from the central veins are observed.

Alcoholic cirrhosis. The final and irreversible form of alcoholic liver disease usually evolves slowly and sidiously. At first the cirrhotic liver is yellow-fatty, and enlarged, usually weighing more than 2 kg. Over the span of years, it is transformed into a brown, shrunken, nonfatty organ, sometimes less than 1 kg in weight. Cirrhosis may develop within 1 to 2 years in the setting of alcoholic hepatitis. Initially the developing fibrous septae delicate and extend from central vein to portal regions as well as from portal tract to portal tract. Regenerative activity of the entrapped parenchymal acini generates fairly uniformly sized «micro-

nodules». With time, the nodularity becomes more prominent; scattered nodules may become large, and occasionally nodules more than 2 cm diameter may develop. As fibrous septae dissect and surround nodules, the liver becomes more fibrotic, loses fat, and shrinks progressively in size. Parenchymal islands are engulfed by ever wider bands of fibrous tissue, and the liver is converted into a mixed micronodular and macronodular pattern. Further ischemic necrosis and fibrous obliteration of nodules eventually create broad expanses of tough, pale scar tissue, leaving residual parenchymal nodules that protrude like «hobnails» from the surface of the liver. By microscopy, the septae contains variable amounts of scattered lymphocytes and some reactive bile duct proliferation.

Complications are subdivided into 2 groups: hepatic and non-hepatic.

Hepatic complication:

1. Progressive hepatic failure.

2. Development of hepatocellular carcinoma.

3. Steatorrhea due to reduced hepatic bile secretion.

4. Gall stones usually of pigment type, are seen twice more frequently in patients with cirrhosis than in general population.

Non-hepatic complication:

1. Portal hypertension and its effects such as ascites, splenomegaly and development collaterals (e.g. esophageal varices, spider nevi etc.).

2. Chronic relapsing pancreatitis, especially in alcoholic liver disease.

3. Infections are more frequent in patients with cirrhosis due to impaired phagocytic activity of reticuloendothelial system.

4. Hematologic derangements such as bleeding disorders and anemia due to impaired hepatic synthesis of coagulation factors and hypoalbuminemia are present.

5. Cardiovascular complications such as atherosclerosis of coronaries and aorta and myocardial infarction are more frequent in these patients.

6. Musculoskeletal abnormalities like digital clubbing, hypertrophic osteoarthropathy.

7. Endocrine disorders such as gynecomastia, testicular atrophy and impotence, whereas in cirrhotic women amenorrhea is a frequent abnormality.

8. Hepatorenal syndrome leading to renal failure may occur in late stages of cirrhosis.

Causes of death are hepatic coma, massive gastrointestinal hemorrhage from esophageal varices, intercurrent infections, hepatorenal syndrome and development of hepatocellular carcinoma.

TUMORS

There are benign tumors, primary and metastatic malignant tumors in the liver. Metastatic malignant tumors are much more common than primary ones. Primary tumors may arise from hepatic cells (hepatocellular tumor), bile duct epithelium (biliary tumor) and mesodermal structures.

Derivation__________Benign___________Malignant_____

Hepatic cells Hepatocellular Hepatocellular

adenoma carcinoma

__________________________________Hepatoblastoma_____

Bile duct epithelium Bile duct adenoma Cholangiocarcinoma (Cholangioma) Combined

hepatocellular and

cholangiocarcinoma

Cystadenocarcinoma

Mesodermal Hemangioma Angiosarcoma

structures__________________________Embryonal sarcoma

Liver cell adenomasare pale, yellow-tan, and frequently bile-stained nodules, found anywhere in the hepatic substance but often beneath the capsule. They may reach 30 cm in diameter. Although they are usually well demarcated, encapsulation may not be macrosco-pically evident. Microscopically, liver cell adenomas are composed of sheets and cords of cells that may resemble normal hepatocytes or have some variation in cell and nuclear size. Portal tracts are absent; instead prominent arterial vessels and draining veins are

distributed through the substance of the tumor. A capsule that ranges from delicate collapsed reticulin to well-defined connective tissue usually separates the lesion from the surrounding parenchyma, but it may be deficient in places or entirely absent.

Bile duct adenomasare firm, pale, and usually single discrete nodules rarely more than 1 cm in diameter, frequently found in a subcapsular location. In contrast to the liver cell adenoma, they are almost never bile stained. Microscopically they are composed of uniformly sized, epithelium-lined channels or ducts separated by a scant-to-abundant connective tissue stroma and sharply demarcated from the surrounding liver.

Hepatocellular carcinoma,cholangiocarcinoma may appear macroscopically as a unifocal (usually large) mass; multifocal, widely distributed nodules of variable size; or a diffusely infiltrative cancer, permeating widely and sometimes involving the entire liver. All three patterns may cause liver enlargement (2000 to 3000 gm), particularly the unifocal massive and multinodular patterns. The diffusely infiltrative tumor may blend imperceptibly into a cirrhotic liver background. When discrete masses can be seen, they are basically yellow-white, punctuated sometimes by areas of hemorrhage or necrosis. Hepatocellular carcinoma sometimes take on a green hue when composed of well-differentiated hepatocytes capable of secreting bile. Cholangiocarcinomas are rarely bile

stained because differentiated bile duct epithelium does not synthesize pigmented bile. All patterns of hepatocellular carcinoma have a strong propensity for invasion vascular channels.

Hepatocellular carcinoma range from well-differentiated to highly anaplastic undifferentiated lesions. In well-differentiated and moderately well-differentiated tumors, cells recognizable as hepatocytic in origin are disposed either in a trabecular pattern or in an acinar, pseudoglandular pattern. Supporting connective tissue is minimal to absent, explaining the soft consistency of most hepatocellular carcinoma. Bile may occasionally be seen in canalicular spaces or lumens between tumor cells, and bile canaliculi may be present ultrastructurally.

A distinctive variant of hepatocellular carcinoma is the fibrolamellar carcinoma. This tumor occurs in young men and women (20 to 40 years of age) with equal incidence, has no association with HBV or cirrhosis factors, and has a distinctly better prognosis. It usually constitutes a single large, hard «scirrhous' tumor with fibrous bands coursing through it. Histologically it is composed of well-differentiated polygonal cells growing in nests or cords and separated by parallel lamellae of dense collar bundles, hence the name «fibrolamellar».

Cholangiocarcinomasresemble adenocarcinomas arising in other parts of the body. Most are well-differentiated sclerosing adenocarcinomas

with clearly defined glandular and tubular structures lined by somewhat anaplastic cuboidal to low columnar epithelial cells. These neoplasms are often markedly desmoplastic, so dense collagenous stroma separates the glandular elements. Mucus is frequently present within cells and the lumina but not bile.

Metastatic tumors in the liver develop resulting metastasis to the liver from the cancer of stomach, breast, lungs, colon, esophagus, pancreas, malignant melanoma. Sarcomas rarely produce metastases to the liver.