Liver



Liver


Ryan O’Hara, MD

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








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 tumor 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 demonstrates the various liver segments.







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.



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


NATURAL HISTORY


General Features



  • Comments



    • Carcinogenesis of HCC in cirrhosis



      • Commonly described as multistep evolution of cirrhotic nodules


    • International Working Party describes 2 types of cirrhotic nodules



      • Regenerative nodules



        • Localized proliferation of hepatocytes and supporting stroma


        • Response to local hepatocellular damage


        • Hyperplasia secondary to deficient portal venous perfusion → early arterial neovascularity


      • Dysplastic nodules



        • Hepatocytes that undergo abnormal growth due to genetic alteration


        • Histologic precursor to HCC


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


        • ↑ arterial neovascularity compared to regenerative nodules


Etiology



  • Risk factors



    • HCC usually occurs in setting of 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: Particular populations found in sub-Saharan Africa and China have a mutated hepatic enzyme that fails to deactivate aflatoxin


        • Activated aflatoxin interacts with specific sites within p53 gene contributing to high incidence of HCC


        • Thorotrast (particularly in development of cholangiocarcinoma)


        • Androgens


        • Hemosiderosis (from repeated blood transfusions)


      • Metabolic disorders



        • α-1-antitrypsin deficiency


        • Hemochromatosis


        • Wilson disease


        • Tyrosinosis


  • Protective factors



    • Universal vaccination of children against HBV in endemic areas (began in Taiwan in 1984 and has markedly decreased HBV infection rate)


Epidemiology & Cancer Incidence



  • Number of cases in USA per year



    • 35,557 (2011)


  • Sex predilection



    • M:F = 8:1 (in countries with high incidence); 2-3:1 (in countries with low incidence)


  • Age of onset



    • Median age of diagnosis is 63 years


  • 3rd leading cause of death from cancer worldwide


  • Accounts for 250,000 deaths worldwide each year


  • Incidence of HCC in developing nations is more than double 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 more than doubled in last 20 years from 2.6 to 7.5 per 100,000 population


    • There is an increased incidence in USA amongst Asian/Pacific Islander men (22:100,000)


    • 75% of cases occur in men compared to women (11.6 vs. 3.9 per 100,000)


    • Racial distribution



      • Caucasian (48%)


      • Hispanic (15%)


      • African American (14%)


      • Other, predominantly Asian (24%)


Genetics



  • Common translocations



    • Aflatoxin acts on guanosine base in codon 249 of p53 tumor suppressor gene leading to a G to T transversion



      • This is often identified in HCC found in regions of sub-Saharan Africa and China, contributing to high incidence in these regions


  • HBV



    • Viral DNA integrates into host’s genomic DNA in tumor cells


    • HBV X protein acts as a transactivator of cellular and viral promoters



      • Disrupts normal cell growth


      • Also binds to p53 tumor suppressor gene


  • Cirrhosis



    • Repeated cycles of cell death and regeneration lead to accumulation of mutations


    • Important component of the pathogenesis of HCV-and HBV-associated liver cancer


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



  • Cholangiocarcinoma



    • 15-20% of primary liver tumors


    • 2nd most common primary liver tumor (80% extrahepatic subtype)


    • 30-50% have nodal spread at presentation


    • 10-20% have distant metastasis at presentation


    • Similar risk factors as hepatocellular, but also



      • Primary sclerosing cholangitis, tobacco smoke, chronic ulcerative colitis in Western countries, and endobiliary infections in Asia (liver flukes)


    • Incidence ↑ in USA (0.7 per 100,000)


    • Average age of diagnosis is 73 years


  • Metastatic disease



    • Secondary liver cancer is ˜ 20x more common than primary


    • Most commonly secondary to colorectal cancer


    • 5-year survival < 5% with hepatic failure most common cause of death


    • Surgical resection may achieve 5-year survival of 37-58% but only 20-25% are eligible


    • Most metastatic cancers are adenocarcinomas that quickly outgrow blood supply and thus have a central necrotic region on imaging


Gross Pathology & Surgical Features



  • Classic macroscopic classification proposed by Eggle in 1901 is 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 histology 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


    • Hep-Par 1



      • Commonly used immunostain for suspected HCC


      • Highly sensitive and specific for hepatocytic differentiation


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 may lead to Budd-Chiari syndrome


      • Portal venous invasion


  • Lymphatic extension



    • 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


  • Hematogenous spread



    • Hematogenous spread is relatively uncommon despite obvious vascular invasion


  • Metastatic sites



    • Distant metastases (in order of prevalence)



      • Lungs


      • Musculoskeletal sites


      • Adrenal gland


      • Peritoneum &/or omentum


IMAGING


Detection



  • 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 gradient-echo 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 may be seen as wedge-shaped region of ↑ perfusion from local portal vein occlusion


        • Some advocate both early and late arterial phases 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 (“coned-beam CT”)


  • MR



    • Most sensitive and specific imaging modality for detection of HCC


    • Considered gold standard for characterization of liver nodules in setting of cirrhosis


    • T1WI



      • Variable signal, depending on degree of fatty metaplasia, fibrosis, and necrosis


      • Generally iso- to hypointense


      • Rarely hyperintense in presence of fat, copper, or glycoproteins


    • T2WI



      • Variable signal although generally hyperintense


      • “Nodule within nodule” occasionally seen (small T2 hyperintense focus within uniformly T2 hypointense dysplastic nodule)


    • T1 C+



      • Small lesions (< 2 cm) generally show rapid arterial enhancement with rapid washout in portal venous and delayed phases


      • Large lesions (> 2 cm) demonstrate heterogeneous nodular enhancement during both arterial and later phases


    • Diffusion-weighted imaging (DWI)



      • Evolving technology used in conjunction with other imaging sequences


      • Useful tool for lesion detection


      • DWI presently limited for lesion characterization; good for follow-up post TACE and radioembolization


  • Arteriography

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Jun 1, 2016 | Posted by in ONCOLOGY | Comments Off on Liver

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