Intrahepatic Biliary Tract Disease and tumors of liver

SECODARY BILIARY CIRRHOSIS 

Prolonged obstruction of extrahepatic biliary tree.

Causes

 - in adults (cholelithiasis, malignancies, surgical strictures)
 - in children (cystic fibrosis, congenital anomalies of biliary tree)

Morphology

 - inflammation > periportal fibrosis > cirrhosis

SECODARY BILIARY CIRRHOSIS 

Autoimmune, chronic, progressive, & often fatal cholestatic liver disease of middle-aged women  

Morphology 

 - destruction of intra-hepatic bile ducts
 - portal inflammation & scarring
 - cirrhosis
 - hepatocellular carcinoma
* presence in 90% of patients circulating antimitochondrial antibodies to bile ducts epithelial cells

PRIMARY SCLEROSING CHOLANGITIS

Inflammation & obliterative fibrosis of intra- & extra-hepatic bile ducts, occurs in the 3^rd through 5^th decades of life, & males predominate by 2:1

Pathogenesis

 - T cells activated in gut mucosa recognize a bile duct antigen that cross-   reacts with gut antigens or enteric bacteria or bacterial products.

 - Antibodies found include (anti-smooth muscle, anti-nuclear, rheumatoid factor, & p-ANCA).

Morphology

 - cholangitis > progressive obliteration & atrophy of bile ducts > scars > cirrhosis
 - surviving ducts become ectatic

Clinical Features

 - asymptomatic patients with persistent elevation of serum alkaline phosphatase - progressive fatigue, pruritus, & jaundice - late outcomes
  * hepatocellular carcinoma
  * cholangiocarcinoma (7%)
  * chronic pancreatitis

Tumors and Tumor-Like Lesions

Presentation

 - Epigastric fullness & discomfort

 - detected by

  1- Routine physical examination 2- Radiographic studies

NODULAR HYPERPLASIAS 

* Focal nodular hyperplasia (solitary)
* Nodular regenerative hyperplasia (numerous)

Common factor in both lesions is focal or diffuse obliteration of portal vein radicles with compensatory augmentation of arterial blood supply

Focal Nodular Hyperplasia

·        Well- demarcated up to many centimeters in diameter most frequently in young to middle - aged adults.

·        Yellowish with central gray-white, depressed stellate scar from which fibrous septa radiate to the periphery.

·        Attributed to long-term use of anabolic hormones or of contraceptives

Liver Cell Adenoma

·        occurs in young women on oral contraceptives.

·        have clinical significance:

 - Mistaken for hepatocellular carcinoma.
 - Subcapsular adenomas may rupture, particularly during pregnancy >life - threatening intraperitoneal hemorrhage.
 - Rarely may transform into carcinoma.

Morphology

 - Grossly
  * well demarcated solitary or multiple nodules up to 30 cm in diameter
  * yellow-tan, & frequently bile-stained         
 - Histology
  * sheets & cords of hepatocytes
  * no portal tracts, instead, prominent solitary vessels are present

MALIGNANT NEOPLASMS

Hepatocellular carcinoma

Cholangiocarcinoma

Hepatoblastoma

Angiosarcoma

Hepatocellular Carcinoma 

* Male:female is 3:1
* Age incidence 20-40 years

* Major etiological factors

 - viral infection (HBV, HCV)
 - chronic alcoholism
 - non-alcoholic steatohepatitis (NASH)
 - food contaminants (aflatoxins)

Pathogenesis

 - Many factors interact (genetic, age, gender, chemicals, hormones, & nutrition)
 - Repeated cell death & regeneration

Morphology

 - Grossly (single mass, multifocal, diffuse)
 - Histologically (differentiated, anaplastic)

Clinical features 

 - non-specific
 - abdominal pain
 - abdominal fullness
 - abdominal mass

Diagnosis

 - radiology
 - biopsy

Natural course    

      
 - progressive enlargement>seriously disturbing hepatic function
 - metastasizes, to lungs & other sites
 - death occurs from
  * cachexia
  * G-I or esophageal variceal bleeding
  * liver failure
  * rupture of tumor with fatal hemorrhage
 - five year survival of large tumors is dismal (death within first 2 years)

Cholangiocarcinoma

* Cancer of bile ducts

* Risk factors

 - Primary sclerosing cholangitis

 - Congenital fibrocholecystic disease of biliary system

 - Previous exposure to Thorotrast

 - Chronic biliary infection by liver fluke

Morphology

-         gross (single mass) 

-         histology (glands formation without bile)

Diagnosis  

 - radiology
 - biopsy
* clinically is detected late as
 - obstruction to bile outflow
 - liver mass

Metastatic Tumors 

* Far more common than primary ones
* the most common primaries
 - breast
 - lung
 - colon
* typically, multiple nodules are produced