Yukio Muramatsu, Tatsuya Yamada,
MD MD
#{149} Shigeru #{149} Susumu
Nawano, Yamasaki,
MD MD
#{149} Kenichi
Early Hepatocellular MR Imaging’ All areas in hepatic lesions designated as adenomatous hyperplasia (All) with malignant foci have recently been recognized as cancer. AH with malignant foci can be classified into two types, depending on the presence of overt cancerous nodules. Lesions without macroscopic nodules are defined as early hepatocellular carcinoma (HCC), while those with a macroscopic component are defined as HCC with early components. A comparative study of early HCC and HCC with early components was performed with magnetic resonance imaging. Early HCC lesions (n = 20) were isointense (n = 11) and hyperintense (n = 9) on Ti-weighted spinecho images and isointense (n = 17), partially hyperintense (n = 2), or hypointense (n = 1) on T2-weighted spin-echo images relative to the surrounding liver. Lesions classified as HCC with early components (n =8) were hyperintense (n = 5), isointense (n = 2), and of mixed signal intensity (n = 1) on T2-weighted images. Tiweighted imaging was superior to T2-weighted imaging in depicting early HCC, but the latter could be useful in evaluating the progression of HCC in the histopathologically early stages. Index
terms:
Liver,
neoplasms, plasms,
cirrhosis,
diagnosis, MR studies,
Radiology
1991;
761.321
761.794 Liver
#{149}
#{149} Liver neo-
O
to the progress in developof various kinds of diag-
WING
ment nostic
imaging
tocellubar
modalities,
chances nodular nodules,
of removing lesions such adenomatous
(All),
atypical
lignant
All,
Atypical
All
Departments
of Diagnostic
Radiol-
partment of Pathology, National Cancer Center Research Institute, Tokyo (S.H.). Received October 2, 1990; revision requested November 14; final revision received April 22, 1991; accepted April 30. Supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health © RSNA,
Address 1991
now
(1-5). This in the
other hepatic as regenerative hyperplasia and
foci from
hepa-
can
reprint
requests
to Y.M.
#{149} Noriyuki
Moriyama,
ing
structure
MD
the
AH
with
cirrhotic
is considered
ma-
liver. an
interme-
diate stage between benign and mabignant lesions. All with malignant foci is thought to be an early stage of HCC. Consensus about the histopathologic
significance
malignant
foci has
in Japan
(6,7).
phasized the
very
well
not
achieved
constitute
differentiated
cancer.
There-
fore, we foci into
classified All with two types, depending
whether a tumor
overt cancerous areas were macroscopically
a nodule, macroscopic
with
and
early
without
defined lesions tumor nodules
components gross
HCC. Along istics
lesions
nodules
clarifying
within seen as
with as HCC
and
tumor
with
of the
malignant on
as early
the character-
magnetic
resonance
(MR)
imaging appearance of these types of HCC, we also evaluated the relationship
between
signal
intensity
and
the
of disease.
From
June
men
and
years
1989 four
[mean,
54-69
six
years
early
METHODS
to June women
62.4 years])
(20 lesions),
with
AND
patients
[mean,
61.0
components
1990,
17 patients
aged
53-71
with (all
early
men
years])
(eight
HCC
aged with
HCC
lesions),
and
contained
(Edmondson
were phy
detected (US),
means
their
of partial
operating
was
MR
imaging
at 1.5 T (MRT 200FX;
Tokyo) was used in this study. Images were obtained with a multisection spinecho (SE) technique performed with use of 600/15 or 20 (repetition time [TR] msec/ echo time [TEl msec) and 2,400/20, 60, or 80 sequences.
Section
thickness
was
lesion
that
had
not
destroyed
as a nodular the
underby-
10
mm with no intersection gap. Two and four signal acquisitions were used for the short TRITE and bong TR/TE sequences, respectively. The short TR/TE images were obtained with a field of view of 35 cm, a 256 x 256 matrix, and no phase wrap. The long TR/TE images were obtained with a field of view of 35-40 cm, a 256 x 256 matrix, and a half-encode reduction. Respiratory and electrocardiographic compensation was not used. The signal intensities and morphologic features seen with each SE sequence were retrospectively compared for early HCC and HCC with early components to reveal the characteristics of early HCC.
RESULTS Sixteen
lesions
cases
were
Four
lesions
20 lesions
of early
found
beside
were were
HCC main
solitary. detected
echo,
In comparison
TE
=
echo
time,
with
TR
=
in 13 tumors.
Nine with
Abbreviations: AH = adenomatous sia, HCC = hepatocellular carcinoma,
defined
system
Toshiba,
examination. was
proved
hepatectomy.
aging.
HCC
II and/or
ultrasonogra-
existence
10 patients (seven men and three women aged 45-76 years [mean, 61.3 years]) with untreated overt HCC (10 lesions) were studied with MR imaging and pathologic Early
5ev-
grade
at operative
and
A superconducting
of AM be-
foci
and
III). The early HCCs ranged from 0.8 to 2.7 cm in diameter (average, 1 .4 cm), and the HCCs with early components ranged from 0.9 to 3.4 cm in diameter (average, 2.0 cm). Overt HCCs ranged from 2.7 to 12.0 cm in diameter (average, 6.2 cm). All lesions
by
et al (6) em-
components
malignant
with
been
Sakamoto
that
sides
of AH
hepatic
eral areas of well-differentiated HCC (Edmondson grade I or grade I and II) (8) in a thin trabecular or acinar formation. However, these areas were not barge enough to be recognized macroscopically. HCC with early components was defined as an early HCC lesion with macroscopically detect-
able nodules
181:209-213
ogy (Y.M., SN., K.T., N.M., T.Y.) and Surgery (S.Y.), National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104, Japan; and the De-
and Welfare.
(HCCs)
be detected and removed has bed to an improvement
(13 the
small
carcinomas
PATIENTS
From
MD MD
Carcinoma:
progression
761.1214
Takayasu, Hirohashi,
#{149} Setsuo
repetition
of the MR
im-
surround-
hyperpla-
SE
=
spin
time.
209
ing
hepatic
were were
parenchyma,
hyperintense isointense
quences. Seventeen (Fig ib), two were small area within
and
one
was
nine
lesions
(Figs la, 2a) and with SE 600/15 sewere
isointense
hypenntense the
in a
tumor
(Fig
hypointense
2b),
with
SE
2,400/60 or 80 sequences. Pseudocapsubes and a nodule within a nodule appearance were
detected
ic,
at gross
2c) or MR
were HCC
examination
imaging.
11
not
(Figs
All lesions
found to be webb-differentiated at histopathobogic examination:
15 were one was
with and
Edmondson Edmondson
grade grade
I (Fig I and
the
grade
I area
predominant,
four
were
grade
I and
id), II
II with
a.
b.
the
grade I area more predominant and the grade II area only slightly recognized (Fig 2d). Fatty components were recognized within tumors in 17 of the 20 lesions (Table 1). On the other hand, seven of eight lesions nents
of HCC with were detected
ing.
Six were
early with
hyperintense,
one
isointense, and one was with a central hypointense
(Fig 3a) with SE 600/15 Five were hyperintense, pointense
with
nodule,
compoMR imag-
and
sequences. one was
a central
two
was
hyperintense nodule
hy-
hyperintense
were
isointense
with
SE 2,400/60 A pseudocapsule
or 80 sequences (Table 2). was detected in lesion (lesion 7). But a nod-
only one ube in nodule
appearance
was
seen
in
three lesions (lesions 4-6) at gross examination (Fig 3b, 3c), and two of these lesions showed mixed signal intensity patterns on MR images. All lesions in this group were well-differ-
entiated and had
HCC overt
Edmondson
HCC
except nodules grade
in addition
II and/or
to the
as hyperintense
T2-weighted lesions had
grade
were
masses
images.
detected
on 10 on
Pseudocapsubes
in nine
of these
lesions.
DISCUSSION HCC
has
multiple
(7,8).
sis is closely
rebated
AH is a proliferative tential to become
210
#{149} Radiology
of a 1.9-cm-diameter
mass
(lesion
18 in Table
1) in the right
lobe of the liver
in a 62-year-old
man. (a) Ti-weighted MR image (600/15) shows a hyperintense pattern. (b) T2-weighted MR image (2,400/60) shows an isointense pattern. (c) Cross section of surgical specimen shows mass (arrows) similar in configuration to the surrounding liver. Pseudocapsule was not seen. (d) Micrograph shows well-differentiated HCC (Edmondson grade I) with acinar structure (arrows) and thin trabecular pattern within the mass (hematoxylin-eosin
stain;
original
magnification,
diagnosed
as early
usually
accompanied
borderline
x200).
Therefore,
atypical
or
this mass
can be differentiated
from
AH and
HCC.
Hepatocarcinogeneto AH,
because
lesion with poHCC (9) and is
by
foci that
cannot
mined to be cancerous ous foci (7,8,10). The
defined as atypical latter as AH with there
are
with
the
and/or cancerformer has been
All (7) and the malignant foci. But
histopathologic
definition
be deter-
problems
of AH with
malig-
nant foci. Sakamoto et ab (7) reported that all the areas of AH with malignant foci were cancerous. Kanai et ab (8) defined a hepatic nodular lesion
with histopathobogic
stages in the course of carcinogenesis or progression in the cirrhotic liver (7). Several types of HCC in the histopathologically earlier stage have been
discovered
Images
III
peripheral
images. Six of these a hypointense pattern
Ti-weighted
1.
for one (lesion 3) composed of
grade I area (Fig 3d). Fatty components were recognized within tumors in seven of these eight lesions. All lesions of overt HCC were
shown
d.
C.
Figure
macroscopically
cancerous scopically,
areas early
ferentiated
and
pia
such
or acinar
as a thin
formation
undetectable as early HCC. MicroHCC is very well dif-
shows
structural
trabecular
and
aty-
pattern
increased
cel-
bubarity with slight nuclear atypia; but it differs from overt HCC in that it has no pseudocapsule and shows no destruction of underlying liver structure
(7,8). On the other hand, HCC with early components has been judged to be a more progressive disease than early HCC because an overt HCC nodule within a tumor is large enough to be detected at gross examination (7) and usually shows hypervascularity (ii). However, a means of diagnosing these types of HCC with use of radiologic imaging has not been established. MR imaging is useful in diagnosing overt HCC, AH, and regenerative nodules (4,5,12,13). Generally,
HCC
shows
a hypo-
overt
or isointense
pat-
tern on Ti-weighted images and a hyperintense pattern on T2-weighted images (5). AH and regenerative nodules show a hyperintense pattern on Ti-weighted images and a hypoin-
tense pattern (12,13).
On
on T2-weighted the
other
hand,
images early
October
HCC
1991
b.
a.
C.
e.
d. Figure
2.
Images
of a 1.7-cm-diameter
mass
(lesion
17 in Table
1) in the right
lobe of the liver in a 62-year-old
image (600/15) shows a hyperintense pattern (arrow) with a central hypointense spot. (b) However, only a hyperintense area on the T2-weighted image (2,400/60). (c) Cross section of surgical specimen shows an mass without a pseudocapsule. (d) Histologic section shows fatty change (J) and Glison sheath (g) within shows well-differentiated HCC (Edmondson grade I) around Glison sheath (g) that shows remodeling of lularity with slight nuclear atypia (hematoxylin-eosin stain; original magnification, x 100). Therefore, this
mainly pattern
showed a hyperon Ti-weighted
an isointense
pattern
images
study.
HCCs aged
in our
in our while
ing treatment) intense pattern imaging. differentiate
on T2-weighted All of the overt (which were im-
study the
or isointense images and
patient
was
demonstrated at T2-weighted
Therefore, early
HCC within
a hyper-
nodules. can be
into two subtypes macroOne has dominant early and small, central overt
nodules
and
a nodule
has
a nodule
appearance
(lesions
and a mixed on MR images
signal intensity (lesions 4 and
181
#{149} Number
4-6
1
in Table
2)
pattern 6 in Ta-
this
subtype
can
be
differentiated from both early HCC and overt HCC with MR imaging. The other subtype (lesions i-3, 7, and 8 in Table 2) has a large overt and scanty early components
HCC
nodule that
were recognized in the periphery of the lesions. Only overt HCC nodules within a tumor could be recognized as hyperintense images. Therefore, may stage
represent than the
The sion
a more former.
has
signal
not
fully
85%
images
of early
HCCs
(cs) and
celHCC.
pattern and 100% of HCCs with early components not having a nodule within a nodule appearance and 100% of overt HCCs had a hyperintense pattern on T2-weighted images. Therefore, we conclude that the signab intensity pattern on T2-weighted images gression
is closely rebated to HCC proand that the presence of a
for
nosis
(12,13). had
(arrows).
structure
Gen-
progres-
erably, AH and regenerative have a hypointense pattern
weighted
mass
(e) Micrograph increased can be diagnosed as early
as
studied.
between
been
cord
MR
the mass is seen yellow-white
pattern
progressive
intensity
the mass
(a) Ti-weighted within shaped,
hyperintense pattern on T2-weighted images depends on the gross size of overt nodules composed of Edmondson grade II or grade III HCC within a tumor. MR imaging is sensitive in the diag-
areas on T2-weighted the latter subtype
relationship and
HCC at gross
examination
Volume
receiv-
it is possible to HCC from overt
HCC, Afl, and regenerative HCC with early components classified scopicably. components
not
bbe 2). Therefore,
woman.
a small part irregularly
nodules on T2-
In our an
study,
isointense
of early
hepatic pattern
extremely erably,
HCC
because
malignant
tumors with a hyperintense on Ti-weighted images are rare, except for HCC. GenT2-weighted
imaging
is useful
Radiology
#{149} 211
in detecting
overt
HCC
(5).
Ti-
weighted imaging was superior to T2-weighted imaging in detection of early HCC in our study. However, ii of the 20 early HCC lesions were not detected due to isointensity on both Ti- and T2-weight#{235}d images. Consequently, other modalities such as computed tomography and/or US or operative US are also necessary to screen for them. Generally, tumors show a hyperin-
tense pattern on Ti-weighted images because of bleeding or fatty degeneration. In our study, there was not one case in which a clear bleeding focus
a.
b.
existed within a tumor, but fatty degeneration was observed in almost all of the lesions. However, except for one lesion (lesion i9), distinct differences
in the
degree
of fatty
compo-
nents were not observed between hyper- and isointense lesions on Tiweighted images, so we could not attribute the hyperintensity simply to the fatty components. Furthermore, evidence of shortening of Ti by a paramagnetic substance could not be obtained. This has an
study shows that iso- or hyperintense
early
Ti-weighted
images
and
tense
with
or without
pattern
hyperintensity ages.
HCC pattern partial
on T2-weighted
Therefore,
we
conclude
of their
patterns
on T2-weighted
imthat
early HCC is an intermediate between AH and overt HCC HCC with early components standpoint
on
an isoin-
signal
lesion and/or from the
2.
3.
U
Yumoto Y, Jinno K, Tokuyama K, et al. Hepatocellular carcinoma detected by iodine oil. Radiology 1985; 154: 19-24. Matsui 0, Kadoya M, Suzuki M, et al. Dynamic sequential computed tomography during arterial portography in the detection of hepatic neoplasms. Radiology 1983; 146:721-727.
Makuuchi al.
M, Hasegawa
The
Figure
H, Yamazaki
S,
Table 1 Relationship HCC
5.
7.
et
HeRadiDi-
tologic studies. Radiology 1986; 159:371377. Sakamoto M, Hirohashi S, Shimosato Y. Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma. Human Pathol 1991; 22:172-178. Kanai T, Hirohashi S, Upton MP, et al. Pa-
8.
212
of small hepatocellular
carcinoma:
a proposal for new gross Cancer 1987; 60:810-819.
classification.
Edmondson
PE.
#{149} Radiology
HA, Steiner
Primacy
(lesion 4 in Table 2) near right hepatic vein in a (600/15) shows hyperintense pattern (arrows)
MR Imaging
Findings
Diameter
(cm)
and
Histopathologic
Fmndings* SE 2,400/60
Sequence
or 80
4
bsointense Isointense Isointense Isointense
5 6 7
1.0 1.1 i.1
Hyperintense Isointense Hyperintense
Isointense Isointense Hyperintenset
8 9 10 11 12 13 14 15 i6 17 18 19
1.2 1.2 1.2 1.2 1.4 1.4 1.5 1.6 1.6 1.7 1.9 2.0 2.7
Isointense Isointense Hyperintense Hypermntense Isointense Hypenntense Isointense Isointense Isointense Hyperintense Hypermntense Hyperintense Hyperintense
Isointense Isointense Isointense Isointense Isointense Isointense Isointense Isointense Isointense Hyperintense Isointertse Isointense Hypermntense
The signal intensity of the lesion was compared t - = not detected, + = mild, + + = moderate, t Lesion was only partially hyperintense. S Grade I area predominant. *
I area
predominant
in Early
Histopathologic
Results
Edmondson Grade
Isointense Isointense Isointense Isointense
20
Results
Sequence
0.8 0.8 0.9 1.0
Grade car-
between
1 2 3
use of operative ultrasound as an resection in patients with hepacarcinoma. World J Surg 1987;
Ito K, Nishimura K, Togashi K, et al. patocellular carcinoma: MR imaging. ology 1987; 164:21-25. Ebara M, Ohto M, Watanabe Y, et al.
thology
mass
SE 600/15 Lesion
agnosis of small hepatocellular carcinoma: correlation of MR imaging and tumor his6.
of a 1.7-cm-diameter
MR Imaging
11:615-621. 4.
Images
65-year-old man. (a) TI-weighted MR image with a central hypointense area. (b) Cross section of surgical specimen shows a mass (arrows) with a nodule within a nodule pattern. (c) Histologic section shows a mass (arrowheads) with necrosis (n) in central nodule due to transcatheter arterial embolization, but another area within the mass is viable (v). (d) Micrograph shows necrotic area (ii) corresponding to the central nodule in c. This area was thought to be a “ghost” HCC of Edmondson grade II. A welldifferentiated HCC of Edmondson grade I showing remodeling of cord structure (cs) and foci of acinar structure is seen on the left side of the image (hematoxylin-eosin stain; original magnification, x40). Therefore, this mass can be diagnosed as HCC with early components.
aid to liver tocellular
3.
intensity
images.
References 1.
d.
C.
with
and
that
+ + +
and grade II area only slightly
I I I I I
+
I I
+
I I I I I I I I I I I I I
of the surrounding =
Fatty Changet
+ +
++ + + +
and
IP
+ + + + +
and and
W II’
and
IP
and
IV
+ -
+ + +
+ + ++ +
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