Liver hyperplasias & neooplasias

Question 1

Solitary or multiple hyperplastic hepatocellular nodules that may develop in the non-cirrhotic Liver

Answer 1

Nodular hyperplasias

Question 2

Causes of focal nodular hyperplasia

Answer 2

Long-term use of Anabolic Hormones or of Contraceptives

Question 3

Epidemioology of focal nodular hyperplasia

Answer 3

Young to middle-aged adults

Question 4

Microscopic features of focal nodular hyperplasia

Answer 4

• Large arterial vessels within central scar, showing fibromuscular hyperplasia & narrowing of their lumen
• Foci of intense lymphocytic infiltrates within the radiating septa
• Marked bile duct proliferation along septal margins
• Normal appearing Hepatocytes in the parenchyma between the septa, but with a thickened plate architecture (typical for regeneration)

Question 5

Macroscopic features of focal nodular hyperplasia

Answer 5

• Well-demarcated but poorly encapsulated nodule
• Lighter colouration than the surrounding Liver
• Central gray-white, depressed stellate scar, with radiations to the periphery

Question 6

Association with conditions affecting intra-hepatic blood flow

Answer 6

Nodular regenerative Hyperplasia

Question 7

Macroscopic features of Nodular regenerative Hyperplasia

Answer 7

Entirely transformed Liver into roughly spherical nodules, in the absence of fibrosis

Question 8

Microscopic features of Nodular regenerative Hyperplasia

Answer 8

• Plump hepatocytes surrounded by rims of atrophic Hepatocytes (reticulin stain
• Complications: Development of Portal Hypertension

Question 9

Most common benign liver tumours

Answer 9

Cavernous Haemangiomas

Question 10

Localisation of Cavernous Haemangiomas

Answer 10

Directly beneath the capsule

Question 11

Macroscopic features of Cavernous Haemangiomas

Answer 11

Size: <2cm in diameter – Discrete, red-blue, soft nodules

Question 12

Microscopic features of Cavernous Haemangiomas

Answer 12

Vascular channels in a bed of fibrous connective tissue

Question 13

What is a hepatic adenoma?

Answer 13

A benign neoplasm of the liver.

Question 14

What is the incidence of hepatic adenomas?

Answer 14

About 1 in 100,000 population.

Question 15

Which population is most commonly affected by hepatic adenomas?

Answer 15

Women using oral contraceptives.

Question 16

What genetic mutations are associated with hepatic adenomas?

Answer 16

HNF1α mutations: Found in 50% of cases.
β-catenin mutations: Found in 15% of cases.

Question 17

Which syndrome is associated with HNF1 mutations?

Answer 17

Maturity-onset diabetes of the young (MODY3).

Question 18

Where are hepatic adenomas most often localized?

Answer 18

Beneath the liver capsule.

Question 19

Describe the macroscopic features of hepatic adenomas.

Answer 19

Size: Up to 30 cm in diameter.
Well-demarcated lesion.
Pale, yellow-tan, and frequently bile-stained.

Question 20

What are the major etiologic factors for hepatocellular carcinoma (HCC)?

Answer 20

Chronic viral infections (HBV, HCV).
Chronic alcoholism.
Nonalcoholic steatohepatitis (NASH).
Food contaminants (e.g., aflatoxins).
Hereditary tyrosinemia (HCC develops in ~40% of cases).

Question 21

How does HCC develop pathologically?

Answer 21

Originates from small-cell, high-grade dysplastic nodules in cirrhotic livers.
Dysplastic nodules are monoclonal with chromosomal aberrations similar to HCC.
Cells of origin: Mature hepatocytes and progenitor (ductular/oval) cells.
Characterized by genomic instability with structural and numeric chromosomal abnormalities.

Question 22

What are the macroscopic features of HCC?

Answer 22

Patterns:
Solitary large mass.
Multifocal nodules of variable size.
Diffusely infiltrative cancer.
Appearance: Paler than surrounding liver, sometimes green-hued.
Propensity for vascular invasion, leading to:
Extensive intrahepatic metastases.
Long snake-like masses in portal vein or inferior vena cava, occasionally extending into the heart.

Question 23

What are the histologic findings in HCC?

Answer 23

Tumour differentiation ranges from well-differentiated to anaplastic/undifferentiated.
Well and moderately differentiated forms:
Hepatocyte-like cells.
Arranged in trabecular, acinar, or pseudo-glandular patterns.
Poorly differentiated forms:
Pleomorphic tumour cells with anaplastic giant cells.
Small, undifferentiated cells.
Cells resembling spindle cell sarcoma

Question 24

What is fibrolamellar carcinoma?

Answer 24

A distinctive variant of hepatocellular carcinoma (HCC).

Question 25

What is the aetiology of fibrolamellar carcinoma?

Answer 25

Unknown

Question 26

What is the epidemiology of fibrolamellar carcinoma?

Answer 26

Accounts for 5% of HCCs.
Occurs in young male and female adults (20-40 years).
Equal incidence in males and females.

Question 27

What are the macroscopic features of fibrolamellar carcinoma?

Answer 27

Single large, hard “scirrhous” tumour.
Characterized by fibrous bands.

Question 28

What are the microscopic findings in fibrolamellar carcinoma?

Answer 28

Well-differentiated polygonal cells with eosinophilic cytoplasm and prominent nucleoli.
Tumour cells arranged in nests or cords, separated by parallel lamellae of dense collagen bundles.

Question 29

How does fibrolamellar carcinoma progress?

Answer 29

Within the liver: Widespread extension via contiguous growth and satellite nodules.
Extra-hepatic metastases:
Vascular invasion into the hepatic vein system.
Late haematogenous metastases (primarily to the lungs).
Lymph node metastases (<50% of cases) to peri-hilar, peripancreatic, and para-aortic nodes.

Question 30

What are the clinical manifestations of fibrolamellar carcinoma?

Answer 30

Ill-defined upper abdominal pain.
Malaise and fatigue.
Weight loss.
Abdominal mass or fullness (occasionally).

Question 31

What might be found on physical examination in fibrolamellar carcinoma?

Answer 31

Enlarged, palpable liver with irregularity or nodularity.

Question 32

What laboratory findings are associated with fibrolamellar carcinoma?

Answer 32

Elevated serum α-fetoprotein (AFP) in advanced tumours (50% of cases).
Immunostaining for Glypican-3 helps distinguish early HCC from dysplastic nodules.
False-positive AFP results in yolk-sac tumours, cirrhosis, chronic hepatitis, and normal pregnancy.

Question 33

What imaging studies are most valuable for detecting fibrolamellar carcinoma?

Answer 33

Ultrasonography, hepatic angiography, CT, and MRI.

Question 34

How is fibrolamellar carcinoma managed?

Answer 34

Resection or ablation for a single small lesion (curative for fibrolamellar variant).
Liver transplantation.
Sorafenib for advanced disease.
Without resection: Median survival is seven months.