Hepatocellular carcinoma (HCC)

What is the most common primary liver malignancy in adults?

Hepatocellular carcinoma (HCC) Summary 1

What is a leading cause of cancer-related mortality worldwide?

Hepatocellular carcinoma (HCC) Summary 2

What is a major risk factor for HCC?

Preexisting liver disease (e.g., cirrhosis, chronic hepatitis) Summary 3

What is a common early feature of HCC?

Often asymptomatic Summary 4

What are some advanced clinical manifestations of HCC?

Abdominal pain, weight loss, and anorexia Summary 5

What screening is recommended for those at risk for HCC?

6-monthly surveillance with abdominal ultrasound with or without serum AFP Summary 6

What is used to confirm the diagnosis of suspected HCC?

Multiphase imaging and liver biopsy (if needed) Summary 7

What are some potentially curative treatment options for HCC?

Tumor resection, liver transplantation, and ablative therapy (e.g., RFA) Summary 8

What are some noncurative treatment options for advanced HCC?

Locoregional therapy (LRT) such as TACE, or systemic chemotherapy Summary 9

What is the general prognosis for HCC?

Poor, due to underlying advanced liver disease Summary 10

What is the global rank of HCC as a malignancy?

Fifth most common malignancy worldwide Epidemiology 11

Where is the highest incidence of HCC?

Southeast Asia and Africa Epidemiology 12

What is the peak incidence of HCC in the US?

70-75 years Epidemiology 13

What is the peak incidence of HCC in Africa and Asia?

30-40 years Epidemiology 14

What is the sex predilection for HCC?

Male > Female Epidemiology 15

What is the primary risk factor for HCC (found in 80% of cases)?

Liver cirrhosis Etiology 16

What are some additional risk factors for HCC?

Chronic hepatitis B or C infection, alcohol-associated liver disease, metabolic dysfunction-associated steatohepatitis (MASH), hemochromatosis, Wilson disease, alpha-1 antitrypsin deficiency, hepatic autoimmune diseases, schistosomiasis, glycogen storage disease, chronic ingestion of aflatoxin Etiology 17

What is aflatoxin and how does it contribute to HCC?

Aflatoxin is a carcinogen produced by Aspergillus flavus. It causes G:C → T:A transversion in codon 249 of TP53 gene, leading to an inactivating mutation Etiology 18

What are the typical early clinical features of HCC?

Usually asymptomatic apart from symptoms of underlying disease (mostly cirrhosis or hepatitis) Clinical features 19

What are some possible clinical features of advanced HCC?

Weight loss, anorexia, hepatomegaly, right upper quadrant tenderness, jaundice, ascites Clinical features 20

How may HCC be detected?

Through screening in at-risk groups or after symptoms develop Diagnosis 21

What is the preferred initial imaging modality for HCC?

Ultrasound abdomen Diagnosis 22

When should further imaging be done in suspected HCC?

Lesion ≥10 mm or lesion of any size and AFP (if performed) ≥ 20 ng/mL Diagnosis 23

When should a liver biopsy be done in suspected HCC?

Inconclusive multiphase imaging or liver lesions suspicious for HCC in patients without cirrhosis Diagnosis 24

When is a liver biopsy NOT routinely needed for HCC diagnosis?

In patients with underlying liver disease and characteristic imaging findings Diagnosis 25

What are some supportive findings on ultrasound for suspected HCC?

Solid nodule(s) typically ≥ 10 mm, of varying homogeneity and echogenicity with irregular borders, signs of cirrhosis may be present Diagnosis 26

What are the indications for multiphase imaging in suspected HCC?

Ultrasound features of HCC, serum AFP ≥ 20 ng/mL, alternative to ultrasound in select patients Diagnosis 27

What are the preferred modalities for multiphase imaging in suspected HCC?

CT or MRI abdomen Diagnosis 28

What is a characteristic finding of HCC with contrast-enhanced imaging?

Arterial phase hyperenhancement followed by portal venous phase washout Diagnosis 29

What lab studies should be obtained in patients with suspected HCC?

CBC, liver chemistries, coagulation screen, serum AFP; additional studies based on suspected paraneoplastic syndromes Diagnosis 30

What might CBC reveal in HCC?

Thrombocytopenia or paraneoplastic erythrocytosis Diagnosis 31

What might liver chemistries reveal in HCC?

May be abnormal in preexisting liver disease or advanced malignancy Diagnosis 32

What might coagulation screen reveal in HCC?

May be abnormal in severe preexisting liver disease or advanced malignancy Diagnosis 33

What is the utility of serum AFP in HCC?

Typically elevated Diagnosis 34

What are the indications for liver biopsy in HCC?

Patients with cirrhosis and inconclusive imaging; Patients without cirrhosis with suspicious lesions Diagnosis 35

What are some risks associated with liver biopsy?

Bleeding, tumor seeding Diagnosis 36

What are some typical findings of HCC on gross pathology?

Often a solitary tumor with a variable appearance, may be nodular or multinodular; may appear hemorrhagic or necrotic Pathology 37

What are some typical histological findings of HCC?

Trabecular pattern of cells, often with thick cords, may have pseudoglandular or solid patterns; cells with variable atypia, may have clear cytoplasm or Mallory bodies; tumor cells may invade vessels Pathology 38

What are the general principles of HCC treatment?

Initiate treatment based on stage of HCC, prevent further deterioration of associated liver disease Treatment 39

What are some curative treatments for very early or early-stage HCC?

Surgical resection (if minimal concomitant liver disease), liver transplantation (if Milan criteria are met), or ablative therapy (e.g. RFA) Treatment 40

What are some treatment options for intermediate-stage HCC

Neoadjuvant (curative)

OR noncurative?

Locoregional therapy (e.g., TACE or transarterial radioembolization) Treatment 41

What are the treatment options for advanced HCC? (Noncurative)

Systemic chemotherapy (targeted or nontargeted) or hepatic arterial infusion chemotherapy Treatment 42

What is the typical approach for end-stage HCC? (Noncurative)

Typically supportive care only Treatment 43

What is the most common malignant liver lesion overall?

Metastatic liver disease Differential diagnoses 44

What are some common primary tumor sites for liver metastases?

Gastrointestinal tract (colon, stomach, pancreas), lung, and breast Differential diagnoses 45

What are some clinical features of liver metastases?

Often asymptomatic; can manifest with nonspecific symptoms, such as malaise, anorexia, weight loss, jaundice, ascites; Features of the underlying primary may be present. Differential diagnoses 46

What are some typical diagnostic findings for liver metastases?

Elevated liver chemistries, Ultrasound (often "bulls-eye" with a hyperechoic center and hypoechoic periphery), multiple hypodense lesions on CT abdomen with IV contrast Differential diagnoses 47

What are some treatment options for liver metastases?

Surgery (if resectable), ablative therapy, systemic chemotherapy, palliative care Differential diagnoses 48

What is hepatic angiosarcoma?

Rare malignant tumor of the liver associated with exposure to vinyl chloride, arsenic, or thorium dioxide Differential diagnoses 49

What are some clinical features of hepatic angiosarcoma?

Nonspecific (abdominal pain, weight loss, jaundice, ascites, anemia), can manifest acutely with hypotension and abdominal pain (hemorrhage) Differential diagnoses 50

What imaging findings are associated with hepatic angiosarcoma?

Variable appearance; single or multiple lesions, typically hypervascular, rapid growth on serial imaging Differential diagnoses 51

What confirms the diagnosis of hepatic angiosarcoma?

Histology: endothelial cells positive for PECAM-1 (CD31) Differential diagnoses 52

What is the prognosis of hepatic angiosarcoma?

Poor (∼ 6 months), often metastatic at diagnosis, high recurrence rate Differential diagnoses 53

What is primary hepatic lymphoma?

A very rare hepatic malignancy associated with HIV, hepatitis B, hepatitis C, and chemical exposure Differential diagnoses 54

What are the clinical features of primary hepatic lymphoma?

Nonspecific; abdominal pain, fatigue, anorexia, weight loss, jaundice, night sweats Differential diagnoses 55

How is primary hepatic lymphoma diagnosed?

Liver biopsy (after imaging studies) Differential diagnoses 56

What is the treatment for primary hepatic lymphoma?

Surgery when possible, followed by chemotherapy Differential diagnoses 57

What is the prognosis of early stage HCC?

5-year survival rate of >70% Prognosis 58

What is the prognosis of advanced HCC?

5-year survival rate of ∼20% (median survival ∼1-1.5 years) Prognosis 59

What are some primary prevention methods for HCC?

Reduce the risk of bloodborne viruses, maintain alcohol intake within normal limits, manage obesity Primary prevention 60

What are some high-risk conditions warranting HCC screening?

Cirrhosis from any cause, chronic hepatitis B (active infection, family history, Asian men >40/women >50, African individuals ≥ 20), Screening 61

What is the preferred screening modality for HCC?

Abdominal ultrasound Screening 62

What screening intervals are recommended for HCC?

Depends on imaging findings; no lesion: repeat US in 6 months; lesion < 10 mm: repeat US in 3-6 months; lesion ≥ 10 mm: perform further imaging Screening 63

When should serum AFP be considered in HCC screening?

If AFP ≥ 20 ng/mL in patient with a lesion of any size, then perform multiphase imaging Screening 64