12-3 Liver Path 8 - Nodules & Tumors Flashcards
What are the 3 general categories of hepatic masses?
Nodular hyperplasia
Benign neoplasms
Malignant tumors
What are the benign neoplasms that affect the liver?
•Benign neoplasms
–Cavernous hemangioma
–Hepatic adenoma
What are the malignant tumors that affect the liver?
•Malignant tumors
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Hepatoblastoma
–Metastatic tumors
What are some clinical pearls to keep in mind when diagnosing hepatic masses?
- Although the emphasis is on primary liver tumours, it is important to remember that metastases far outnumber primary tumours and so these are always considered in differential diagnosis.
- The clinical scenario is an important feature in the differential diagnosis of any mass lesion in the liver. Age, gender and predisposing factors such as underlying liver disease or exposure to drugs, chemicals or parasites influence the likelihood of development of many tumours
- Consequently, one should be very circumspect about diagnosing a tumour of infancy, like hepatoblastoma, in an adult or a tumour like hepatocellular adenoma that is strongly associated with oral contraceptive steroids in an elderly male.
Describe the cells and structures involved in focal nodular hyperplasia.
- Composed of hyperplastic nodules of hepatocytes, separated by fibrous septa which often form typical stellate scars
- Absence of true bile ducts and a connection to the biliary outflow tract
- Estrogen can enhance growth, but do not cause FNH
What is the hypothesis behind the pathology of focal hodular hyperplasia?
Hypothesis
•Focal nodular hyperplasia is usually thought to be due to hyperplastic growth of normal hepatocytes with a malformed biliary draining system and/or pre-existent arteriovenous malformation. The arterial supply is derived from the hepatic artery whereas the venous drainage is into the hepatic veins. FNH does not contain portal venous supply.
What are the demographics behind focal nodular hyperplasia?
- Most commonly found in adult women (20-30 yo)
- Benign, second most common benign tumor of the liver, after hemangioma
What are the diagnostic features of focal nodular hyperplasia?
•Diagnostic features of fibrous septa with a ductular reaction and irregularly thickened arteries unaccompanied by bile ducts, lying against nodular proliferation of hepatocytes without portal tracts or central veins.
What’s this?
Focal nodular hyperplasia
Resected and bisected specimen shows a discrete nodule with central scar. Normal liver tissue is not present
•Stellate scar with nodular parenchyma
What’s this?
Gross appearances of focal nodular hyperplasia
What’s this?
Focal nodular hyperplasia
Fibrosis with ductular proliferation
What happens in nodular regenerative hyperplasia?
- Liver is entirely transformed into nodules grossly similar to micronodular cirrhosis but without fibrosis
- Thought to represent a chronic ischemic injury secondary to disturbance to the blood flow (such as sinusoidal obstructive syndrome) within the liver
What is associated with nodular regenerative hyperplasia?
- Can be associated with the development of portal hypertension
- Thought to be a regenerative response to vascular injury (small vessel vasculitis??)
- Thought to represent a chronic ischemic injury secondary to disturbance to the blood flow (such as sinusoidal obstructive syndrome) within the liver
What can cause nodular regenerative hyperplasia?
•Chronic use of medications (commonly associated drugs include thiopurines, chemotherapeutic agents, and antiretroviral agents) can cause NRH
azathioprine- Treat autoimmune disease, transplant patient IBD
mercatopurine- Therapy for acute (lymphocytic,lymphoblastic) leukemia
•May be reversible with medication withdrawal
What’s this?
Nodular regenerative hyperplasia
There is sinusoidal dilation present (arrows). There are no inflammatory infiltrates, fibrosis and no areas of necrosis.
What are the SSXs of nodular regenerative hyperplasia?
- Nodular regenerative hyperplasia (NRH) is a form of noncirrhotic portal hypertension that can be caused by chronic use of medications.
- NRH typically presents with the insidious or unexpected onset of signs or symptoms of portal hypertension (weakness, ascites, splenomegaly, esophageal varices) in a patient with little evidence of chronic liver disease. The diagnosis is made by liver biopsy, showing absence of significant fibrosis and presence of nodularity usually best defined by reticulin staining. On superficial review, the liver biopsy may appear normal.
Serum enzymes are only modestly elevated and, by themselves, would be little matter of concern. The presence of jaundice, symptoms of fatigue and fluid overload with ascites and edema, however, indicates that the injury is potentially severe
What does nodular regenerative hyperplasia give rise to?
non-cirrhotic portal HTN
What is hepatic adenoma, and what is it associated with?
•Benign tumor of hepatocytes in young women taking oral contraceptives (increased 30-40 fold)
–If in males, associated with anabolic steroids
Why is the location of hepatic adenoma important?
•Subcapsular location prone to rupture especially in pregnancy. Resect if > 5cm or symptomatic, cessation of sex hormones can lead to full regression
Describe the histopathology of hepatic adenoma.
- Hepatocellular adenoma (HCA) is a benign neoplasm. HCA is composed of benign hepatocytes arranged in sheets and cords without acinar architecture. HCA lacks the central scar and large arteries of focal nodular hyperplasia.
- Diagnosis of HA is made on the basis of benign hepatocytes regularly arranged separated by non-dilated sinusoids but completely lacking portal tracts
What are the 3 subtypes of hepatic adenoma?
HNF1-alpha Inactivated hepatocellular adenoma
Beta-catenin activated hepatocellular adenomas
Inflammatory hepatocellular adenoma
What population is HNF1-alpha inactivated hepatocellular adenoma most commonly found in?
women
What is important pathologically about beta catenin activated hepatocellular adenomas?
•β-Catenin Activated Hepatocellular Adenomas (minority of adenomas)
–Very high risk for malignant transformation
–Often have a high degree of cytologic or architectural dysplasia
What populations does inflammatory hepatocellular adenoma affect?
both men and women
What is inflammatory hepatocellular adenoma associated with? Benign or malignant?
–Associated with non-alcoholic fatty liver disease
–Small but definite risk of malignant transformation
What’s this?
Hepatic adenoma
rounded smooth borders and no central scar
•Hepatic adenoma typically develop in women in the reproductive age group (15–45 years), nearly always associated with oral contraceptive steroid use. The incidence of OCP-related adenomas appears to have decreased in recent decades with the introduction of lower dose oral contraceptive preparations
What’s this?
Hepatic adenoma that lead to fatal hemorrhage