Hepatocellular Carcinoma



Hepatocellular Carcinoma


Jeffrey Olpin, MD

































































(T) Primary Tumor

Adapted from 7th edition AJCC Staging Forms.


TNM

Definitions


TX

Primary tumor cannot be assessed


T0

No evidence of primary tumor


T1

Solitary tumor without vascular invasion


T2

Solitary tumor with vascular invasion or multiple tumors, none > 5 cm


T3a

Multiple tumors > 5 cm


T3b

Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein


T4

Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum


(N) Regional Lymph Nodes


NX

Regional lymph nodes cannot be assessed


N0

No regional lymph node metastasis


N1

Regional lymph node metastasis


(M) Distant Metastasis


M0

No distant metastasis


M1

Distant metastasis


(G) Histologic Grade


G1

Well differentiated


G2

Moderately differentiated


G3

Poorly differentiated


G4

Undifferentiated

















































AJCC Stages/Prognostic Groups

Adapted from 7th edition AJCC Staging Forms.


Stage

T

N

M


I

T1

N0

M0


II

T2

N0

M0


IIIA

T3a

N0

M0


IIIB

T3b

N0

M0


IIIC

T4

N0

M0


IVA

Any T

N1

M0


IVB

Any T

Any N

M1








Gross specimen shows a solitary fibrolamellar hepatocellular carcinoma without vascular invasion. Note well-circumscribed tumor image with radiating fibrous septa that merge to form a central scar image.






Micrograph of H&E stained section of a solitary HCC shows fairly well-defined tumor margins image. The tumor is immediately deep to the liver capsule image. (Original magnification 10×.)






Higher magnification of the preceding figure shows sheets and nests of small neoplastic cells with abdundant eosinophilic cystoplasm image. Lamellar pink fibrous strands image are seen separating nests and sheets of malignant cells. (Original magnification 400×.)






Gross specimen shows multiple small tumor nodules image, none measuring more than 5 cm.







Micrograph of H&E stained section of a solitary hepatocellular carcinoma shows tumor cells image infiltrating a fibrotic background image. Tumor cells image are likewise seen infiltrating dilated vascular spaces. The presence of vascular invasion makes this tumor T2. (Original magnification 100×.)






Higher power micrograph of preceding image shows a small blood vessel lined by endothelial cells image. There is direct vascular infiltration of neoplastic hepatocellular carcinoma cells image.






Gross specimen shows multiple discrete tumor nodules image, some of which measure more than 5 cm.






Micrograph of H&E stained section shows extensive tumoral invasion image into the distended portal vein image. Inset shows a major hepatic vessel wall image with extensive tumoral infiltration of the vessel lumen image. Invasion of large vessels constitutes T3b disease. (Original magnification 100×.)







Graphic shows a solitary tumor without vascular invasion, consistent with T1 disease.






Graphic shows a solitary tumor with small vessel invasion image, consistent with T2 disease.






Graphic shows multiple tumors throughout the liver, all of which are smaller than 5 cm. No vascular invasion is seen, consistent with T2 disease.






Graphic shows multiple tumors throughout the liver measuring more than 5 cm, consistent with T3a disease.







Graphic shows a solitary tumor with adjacent invasion of the portal vein image, consistent with T3b disease.






Graphic shows multiple tumors throughout the liver with portal venous invasion image. The presence of major vascular invasion, whether associated with a single or multiple tumors, is considered T3b disease.






Graphic shows multiple tumors throughout the liver, some of which demonstrate extracapsular extension image. Extracapsular tumoral extension with perforation of the visceral peritoneum is consistent with T4 disease.






Graphic shows multiple tumors throughout the liver. There is extracapsular tumor extension with invasion of the adjacent duodenum image and stomach image, consistent with T4 disease. Invasion of the gallbladder wall would not be classified as T4.







Graphic shows regional lymphadenopathy for metastatic hepatocellular carcinoma. These include paraceliac, hilar (common bile duct, hepatic artery, portal vein, and cystic duct), paraaortic, and portocaval lymph nodes.






Graphic shows thoracic lymph nodes in metastatic hepatocellular carcinoma. These include a) pretracheal, b) right paratracheal, c) left paratracheal, d) right hilar, e) aortopulmonary, f) anterior mediastinal, g) left hilar, and h) cardiophrenic lymph nodes.


















image

METASTASES, ORGAN FREQUENCY


Lung

55%


Bone

28%


Adrenal gland

11%


Peritoneum/omentum

11%




OVERVIEW


General Comments



  • Most common primary hepatic malignant tumor


  • Synonymous with hepatoma


Classification



  • Hepatocellular carcinoma (HCC)



    • Usually occurs in setting of cirrhosis


    • Poor prognosis


  • Fibrolamellar carcinoma



    • Relatively rare variant of HCC


    • Does not occur in setting of cirrhosis


    • Better prognosis than conventional HCC


PATHOLOGY


Routes of Spread



  • Local spread



    • 3 distinct intrahepatic forms have been commonly described



      • Solitary massive tumor


      • Multiple nodules scattered throughout liver


      • Diffuse infiltration of liver


    • Vascular invasion commonly seen



      • Hepatic vein invasion leads to Budd-Chiari syndrome


      • Portal venous invasion


  • Lymphatic spread



    • Regional lymphadenopathy implies N1 disease by TNM criteria


    • Regional nodal involvement (in order of prevalence)



      • Periceliac


      • Portohepatic


      • Paraaortic


      • Portocaval


      • Peripancreatic


      • Aortocaval


      • Retrocaval


    • Distant lymphadenopathy (in order of prevalence)



      • Mediastinal


      • Cardiophrenic


      • Mesenteric


      • Internal mammary


      • Perirectal


      • Retrocrural


      • Iliac


      • Paraspinal


  • Distant metastases (in order of prevalence)



    • Lungs


    • Musculoskeletal sites


    • Adrenal gland


    • Peritoneum &/or omentum


General Features



  • Comments



    • Carcinogenesis of HCC in cirrhosis



      • Commonly described as multistep evolution of cirrhotic nodules


    • International Working Party nomenclature describes 2 types of cirrhotic nodules



      • Regenerative nodules



        • Localized proliferation of hepatocytes and supporting stroma


        • Occur as response to local hepatocellular damage


        • Undergo hyperplasia due to deficient portal venous perfusion → early arterial neovascularity


      • Dysplastic nodules



        • Composed of hepatocytes that undergo abnormal growth due to genetic alteration


        • Histologic precursor to HCC


        • Small HCCs (< 2 cm) are often histologically indistinguishable from dysplastic nodules


        • Increased arterial neovascularity compared to regenerative nodules


  • Genetics



    • Hepatitis B virus (HBV) DNA integrated into host’s genomic DNA in tumor cells


  • Etiology



    • HCC usually occurs in setting of underlying cirrhosis (90%)


    • Common causes of cirrhosis include



      • Viral hepatitis (individuals with chronic hepatitis are at 20x greater risk of developing HCC)



        • Hepatitis C virus (accounts for 55% of cirrhosis)


        • Hepatitis B virus (accounts for 16% of cirrhosis)


      • Alcoholism


      • Carcinogens



        • Aflatoxins


        • Thorotrast


        • Androgens


        • Hemosiderosis (from repeated blood transfusions)


      • Metabolic disorders



        • α-1 antitrypsin deficiency


        • Hemochromatosis


        • Wilson disease


        • Tyrosinosis


  • Epidemiology & cancer incidence



    • 3rd leading cause of death from cancer worldwide


    • Accounts for 250,000 deaths worldwide each year


    • Incidence of HCC in developing nations is over 2x that of developed countries



      • Incidence of HCC is highest in Asia and Africa due to high prevalence of hepatitis B and C


    • Frequency in United States



      • Incidence in USA has doubled in last 20 years from 2.6 to 5.2 per 100,000 population


      • Average age at diagnosis is 65 years


      • 75% of cases occur in men


      • Racial distribution



        • Caucasian (48%)


        • Hispanic (15%)


        • African-American (14%)


        • Other, predominantly Asian (24%)


  • Associated diseases, abnormalities



    • Fibrolamellar carcinoma



      • Variant of hepatocellular carcinoma


      • Relatively rare neoplasm with better prognosis than conventional HCC


      • Occurs most commonly in absence of cirrhosis


      • Affects younger age group with peak incidence at 24.8 ± 8 years


      • Higher incidence among Caucasians


      • No gender predilection



Gross Pathology & Surgical Features



  • Classic macroscopic classification proposed by Eggle in 1901 still used today



    • Nodular



      • Smaller and more distinct than massive lesions


      • Sharper margins


    • Massive: 2 dominant forms



      • Composed of confluent small tumors


      • 1 large lesion occupying almost entire liver


    • Diffuse



      • Multiple infiltrating lesions occupying large part of liver


Microscopic Pathology



  • H&E



    • Edmondson grading system widely used to grade histologic tumor differentiation of HCC



      • Grade I



        • Tumor cells similar in size to normal hepatocytes


        • Arranged in relatively thin trabeculae


        • Acini containing bile are rare


      • Grade II



        • Cells larger than normal hepatocytes


        • Hyperchromatic nuclei occupy greater proportion of cells


        • Thicker trabeculae


        • Acini containing bile are common


      • Grade III



        • Hepatocytes with large nuclei that occupy > 50% of cytoplasm


        • Trabeculae still dominant, although isolated cells may be present


        • Giant and bizarre cells common


        • Bile is rarely present


      • Grade IV



        • Cells contain nuclei that occupy most of cytoplasm


        • Predominantly solid areas with little or no bile


        • Intravascular and intrasinusoidal growth common


  • Special stains



    • Reticulin stain commonly used to visualize reticular fibers


    • HepPar 1



      • Commonly used immunostain for suspected HCC


      • Highly sensitive and specific for hepatocytic differentiation


IMAGING FINDINGS


Detection



  • HCC commonly occurs in setting of chronic liver disease &/or cirrhosis



    • Frequently results as final manifestation in continuum of nodular liver disease


  • Cirrhosis alters normal liver morphology with variable degree of



    • Fibrosis


    • Scarring


    • Nodular regeneration


    • Altered hepatic perfusion



      • Portal hypertension


      • Portal venous occlusion ± reversal of flow


  • Regenerative nodules



    • Ultrasound



      • Plays little role in detection of discrete liver nodules


      • Liver margins may demonstrate nodular contour in setting of macronodular cirrhosis


    • CT



      • Nodules poorly visualized on NECT


      • Enhancement similar to background parenchyma on CECT


      • Siderotic nodules may be occasionally seen as hyperdense on NECT


    • MR



      • T1WI



        • Nonsiderotic nodules can occasionally be detected as slightly hyperintense


        • Siderotic nodules well visualized on gradientecho images, but rarely seen on spin-echo images


      • T2WI



        • Nonsiderotic nodules rarely seen


        • Siderotic nodules well visualized as discrete hypointense foci


      • T1 C+



        • Nonsiderotic nodules poorly visualized (may very rarely demonstrate arterial phase enhancement)


        • Siderotic nodules commonly seen as hypointense foci


  • Dysplastic nodules



    • Ultrasound



      • Plays little role in detection of liver nodules


    • CT



      • Nodules may occasionally be seen as hyperdense on NECT


      • Generally isodense to liver on CECT


    • MR



      • T1WI



        • Large nodules may be homogeneously hyperintense


      • T2WI



        • Large nodules may be homogeneously hypointense


      • T1 C+



        • Enhancement rare


        • Mimics HCC when seen


  • Hepatocellular carcinoma



    • Ultrasound



      • Usual modality of choice for screening of HCC in cirrhotic patient



        • Most affordable imaging modality


        • No ionizing radiation


      • Echogenicity of HCC highly variable


      • Small lesions (< 5 cm) are usually hypoechoic



        • Thin hypoechoic halo corresponding to fibrous capsule commonly seen


      • Larger lesions (> 5 cm) are generally mixed echogenicity



        • Hyperechoic areas can be seen in setting of intratumoral fat


        • Hypoechoic regions commonly seen in setting of necrosis


      • Color Doppler




        • Neovascularity and arteriovenous shunting may be seen


        • High velocity waveforms characteristic, albeit nonspecific


        • Power Doppler signal variable; cannot be used to reliably distinguish HCC from metastatic disease


  • CT



    • NECT



      • Visualization generally limited without IV contrast


      • Lesions are usually hypodense if detected



        • Patchy fat attenuation may be seen in lesions with intratumoral fat


        • Fluid attenuation may be seen with tumoral necrosis


    • CECT



      • Arterial phase



        • Avid homogeneous enhancement in small lesions


        • Heterogeneous enhancement in larger lesions


        • Transient hepatic attenuation difference (THAD) may be seen as wedge-shaped region of increased perfusion from local portal vein occlusion


        • Some investigators advocate both early and late arterial phases in order to overcome differences in blood flow kinetics and tumor characteristics


      • Portal venous phase



        • Small lesions usually not detectable due to washout


        • Larger lesions may retain variable degree of enhancement


      • Delayed phase



        • Both small and large lesions generally not well visualized


      • Hepatic artery catheter CT



        • Invasive procedure requiring selective catheterization of hepatic artery


        • May reveal small lesions not seen during routine intravenous arterial phase studies


        • May potentially alter treatment options


  • MR findings

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Sep 18, 2016 | Posted by in GASTROINTESTINAL IMAGING | Comments Off on Hepatocellular Carcinoma

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