imagin g of hepatocellular carcinoma

1. IMAGING OF HEPATOCLULLUR
CARCINOMA
Pradeep Kumar

2. HCC
• 5th most common neoplasm
• 3rd most common cause of cancer-
related deaths
• M:F=5:1
• Risk factors: cirrhosis, Hep B and C virus
infn, alcoholism, and aflatoxin, NASH
• Macronodular or posthepatitis cirrhosis
most frequently associated with HCC,
and micronodular cirrhosis less often.
• Periodic ultrasonography and serum alfa
feto protein (every 3 to 6 months)
allows early HCC detection

3. •Symptoms:
•Small, localized tumors: usually-
asymptomatic.
•Advanced terminal stage: hepatomegaly,
upper abd mass, abd pain, general malaise,
anorexia, abd fullness, wt loss, jaundice,
ascites, edema, GI bleed

4. • Two types of human hepatocarcinogenesis:
• de novo carcinogenesis
• multistep carcinogenesis in liver with
cirrhosis or chronic hepatitis
• Progression: Regenerative nodule ->
dysplastic nodule (DN) DN with malignant
foci (early HCC) early HCC with definitely
well-differentiated HCC foci moderately or
poorly differentiated hepatocellular
carcinoma
• Change in blood supply: with progression,
PV & normal HA supply , abnormal HA
supply increases

5. • MRI SI also useful to estimate the grade of
malignancy of hepatocellular nodules
• With progression,
–T2WI SI increases
–T1WI SI decreases
–SPIO (RES specific) CM accumulation decreases
–Hepatocyte specific CM accumulation decreases

8. Early HCC
• indistinct margin, hypoattenuation or isoattenuation
• decreased but not absent intranodular portal supply
• High SI T1WI & iso/hypointensity on T2WI
• occasional fatty changes
• SPIO usually accumulates in early HCC

11. Classic Hypervascular HCC
•Microscopically, majority are moderately differentiated.
•Macroscopically, simple nodular/ simple nodular with
extranodular growth, confluent multinodular type, or
infiltrative type
•Larger tumors: internal necrosis, hmg, and scarlike changes
•Advanced lesions: cancer cells often invade portal & hepatic
veins, forming tumor thrombi

12. •NCCT:
•Hypodense area may be seen
because of fatty changes
•Calcification is rare
•Copper accumulation/ hmg
slight hyperdensity

13. Arterial phase:
• Enh of entire lesion; intensity differs
with mosaic architecture (distinctive
finding of HCC)
• Poorly differentiated HCC relative
hypovascularity with infiltrative
growth
• Fibrous capsule: hypodense in NCCT;
hyperdense in delayed

14. CONFLUENT MULTINODULAR HCC INFILTRATIVE HCC

15. • T1WI:
• low SI
• 1/3rd cases high SI (fatty metamorphosis in 1/3rd
cases, Cu, glycogen & high-grade cancer cell
differentiation in 2/3rd cases)
• Low SI rim of capsule
• T2WI: high SI, capsule high SI
• T1 low & T2 high SI combination
• Unique among hepatic malignant tumors except
for metastasis from malignant melanoma
• Almost diagnostic for HCC, esp in high-risk pts.
• SPIO & hepatobiliary agents do not accumulate in
classic HCC; but in some well diff HCC

16. Tumour Thrombus
• Tumor thrombus in main PV, 1st/2nd
branches of intrahepatic PV, or major
branches of HV intravascular solid
mass lesion.
• DDx from blood thrombus usually
possible by enh
AP shunting with thread and streak signs
can be seen on dynamic CT
• Area with obstructed PV shows
segmental staining  important sign of
peripheral PV invasion by HCC.
• Portal vein diameter > 23 mm with
arterial enhancement

18. USG
•Variable appearance
•Hypoechoic: most <5cm (no necrosis)
•Complex: with time & enlargement
(fibrosis/necrosis)
•Hyperechoic: small (fatty
metamorphosis/sinusoidal dilatation).

19. Color doppler:
•Characteristic high
velocity signals
•Neovascularity in tumour
thrombi in PV (diagnostic
of HCC )

20. HCC with Atypical Histologic Features
Fatty metamorphosis
Scirrhous
Massive necrosis
Intratumoural hmg
Cu accumulation
Sarcomatous changes
Growth in bile ducts

21. Fatty metamorphosis
•Usually diffuse in small HCCs &
focal in larger tumors
•echogenic on US, hypodense on
CT, & high SI on T1WI.
•When severe, <10HU in tumor,
Dx of fat component possible
•Specific detection of fatty
deposition, chemical shift MRI
useful.

22. Scirrhous
• Abundant fibrous stroma
separating cords of tumor cells
• Hypovascularity in arterial
phase & delayed enhancement
in delayed phase
• DD-confluent hepatic fibrosis,
granuloma & cholangioCa

23. Spontaneous massive necrosis:
• Small HCC with fibrous capsule
• Nonenhanced cystic mass with
irregular wall
Intratumoral hemorrhage :
• NCCT- relatively massive,
intratumoral or peritumoral
hyperdensity.
• On dynamic CT a pseudoaneurysm
may be visualized.
• Intraperitoneal hmg usu a/w
subcapsular HCC rupture

24. •Copper accumulation: marked
Cu accumulation show
hyperdensity (50 to 60 HU)
(abundant Cu-binding protein in
cancer cells). High SI on T1WI.
•Sarcomatous changes:
sporadic; hypodense or avascular in
arterial phase

25. •Tumor growth into bile
ducts:
A cast like defect with smooth
margin (differentiates it from
bile duct cancer)

26. Extra point --
• The key pathological feature of early HCCs which is helpful
for differentiating them from HGDNs is stromal invasion,
which is defined as the infiltration of tumor cells into the
fibrous tissue surrounding the portal tracts and replacing
growth.
• Heat shock protein-70, glutamine synthetase and glypican-3
by immunohistochemical stains is a useful adjunct in
distinguishing early HCC from DNs .

27. • The key pathological feature of early HCCs which is helpful
for differentiating them from HGDNs is stromal invasion,
which is defined as the infiltration of tumor cells into the
fibrous tissue surrounding the portal tracts and replacing
growth.
• Heat shock protein-70, glutamine synthetase and glypican-3
by immunohistochemical stains is a useful adjunct in
distinguishing early HCC from DNs .

28. Key Alterations during Hepatocarcinogenesis
• During the hepatocarcinogenesis, Kupffer cell density,
hepatocyte function, portal tracts and organic anionic
transporting polypeptide (OATP) expression simultaneously
and gradually decrease, while sinusoidal capillarization and
recruitment of unpaired arterioles develop.
• Intranodular fat content usually increases in early
hepatocarcinogenesis, but regresses in progressed HCC

29. Angiogenesis and Venous Drainage
• The vascular supply of DNs is derived from unpaired arteries
and portal tracts, which are induced by growth factor
produced by lesional cells.
• In small and early HCCs, neoangiogenesis is not fully
developed

31. Fat and Iron Contents
• early stage of hepatocarcinogenesis, LGDNs, HGDNs, and early
HCCs show increased fat accumulation in the hepatocytes
• Forty percent of early HCCs manifest diffuse fat accumulation.
• Iron accumulation occurs preferentially in LGDNs and in some
HGDNs. With further de-differentiation, most HGDNs, early
HCCs, an progressed HCCs become iron free.

32. OATP Transporters
• OATP expression levels are high in RNs and LGDNs and lower
in many HGDNs, early HCCs, and progressed HCCs.
• During hepatocarcinogenesis, OATP8 expression level
decreases prior to complete neoangiogenesis.

33. Computed Tomography
• Most DNs show iso- or hypoattenuation on arterial, portal
venous, and delayed-phase images because of the relatively
preserved hepatic arterial flow.
• However, hepatic arterial flow in some HGDNs increases owing to
neo angiogenesis resulting in the potential misdiagnosis of a
hypervascular HCC.
• On dynamic contrast-enhanced CT, most early HCCs also did not
show arterial-phase hyperenhancement because of preservation
of the portal venous flow

34. Magnetic Resonance Imaging
• Pathological characteristics of an increased cellular density,
arterioportal imbalance, and decreased OATP expression
during the hepatocarcinogenesis could be evaluated by
various MRI techniques
• This protocol includes at least 3 dynamic phases: the late
hepatic arterial, portal venous (50∼70 s after contrast
injection), and delayed (2∼3 min) phases.

35. • Some DNs, especially HGDNs, contain higher intracellular fat than
the background liver . The nodules manifest as hyperintensity on
T1-weighted in-phase images
• The presence of restricted diffusion favors the diagnosis of
malignancy and helps differentiate HCCs from DNs because
restrictive diffusion reflects tissue hypercellularity
• current reports, Gd-EOB-DTPA-enhanced MRI enables the accurate
detection and characterization of HCCs and has demonstrated an
increased sensitivity for the detection of HCCs.

36. •However, because OATP8 expression decreases during
hepatocarcinogenesis prior to complete neoangiogene
increased arterial flow, borderline hepatic nodules can be seen
as nonhypervascular and hypointense nodules on HBP
•On Gd-EOB-DTPA-enhanced MRI, a considerable number of
early HCCs, and some HGDNs, are hypointense on HBP due to
underexpression of OATP

38. THANK YOU