Imaging detection of diffuse hepatocellular carcinoma

(HCC): Comparison of ultrasound, CT and MRI in small

infiltrative HCC and diffuse dissemination types

Poster No.: C-0030

Congress: ECR 2010
Type: Scientific Exhibit
Topic: Abdominal Viscera (Solid Organs)
Authors: M. A. Hernandes, J. Elias Jr, A. C. Teixeira, V. F. Muglia,
M. Koenigkam-Santos, F. F. Souza, A. L. C. Martinelli, A. K.
Sankarankutty, O. Castro e Silva; Ribeirão Prêto/BR
Keywords: hepatocellular carcinoma, diffuse type, cirrhosis
DOI: 10.1594/ecr2010/C-0030

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Page 1 of 17
Purpose

HCC has 3 growth patterns: solitary lesion, multifocal or multinodular pattern and
the diffuse type [1]. Diffuse-type HCC has been considered as an extensive and
infiltrative tumor with ill defined margins, frequently accompanied by portal venous
tumor thrombosis and high level of serum #-fetoprotein (AFP) [3,4,5,6]. Clinical and
pathological findings of diffuse-type HCC were described by Okuda et al [4] in 1981 in
six patients. Clinical features were characterized by rapid deterioration of the patient's
general condition, with hepatic failure, fast enlargement of the liver size and abdominal
pain. Pathologically the liver presented multiple minute, uniformly sized tumor nodules,
some of them grossly indistinguishable from cirrhotic nodules.

1. The major purpose of this study was to review the imaging findings of diffuse HCC.

2. We also aimed to present differences between small infiltrative HCC and diffuse intra-
hepatic HCC dissemination.

Methods and Materials

Patients:

A retrospectively active search was carried out in the radiologic and clinical databases
of Ribeirão Preto University Hospital, a regional reference Hospital for 1.000.000
inhabitants, from January 2001 to September 2009, looking for diffuse HCCs, based on
imaging criteria. Twenty-six out of 180 patients with diagnosed HCC (14.4%) met the
criteria for diffuse-type HCC (21 men (80.7%) and 5 women (19.3%); mean age of 55 +/-
11.8 years, ranging from 18 to 72 years).

Imaging criteria - modified from Kanematsu et al [3]:

1) no distinct margination on any portion of the tumor;

Page 2 of 17
2) permeative appearance;

3) patchy or miliary enhancement corresponding to the tumors on the early-phase

postcontrast CT and/or MR images (fig. 1).

Additional criteria:

• Neoplasic portal venous thrombosis characterized by expansive intra-portal

mass with early-phase postcontrast enhancement with no visualization of
well-defined hepatic mass lesion (fig. 2,3).

• Small infiltrative diffuse-type HCC were characterized when the imaging

findings were restrict to a hepatic segment only (fig. 4).

Images for this section:

Page 3 of 17
Fig. 1: Diffuse-type HCC with portal vein thrombosis. CT images, non enhanced (A);
postcontrast arterial phase (B), portal venous phase (C) and intersticial phase (D).
Extensive liver lesion with ill-defined margins and patchy enhancement, associated
with expansive intra-portal mass, which has an early-phase postcontrast enhancement
(arrow, B).

Page 4 of 17
Fig. 2: Diffuse-type HCC with portal vein thrombosis. Color Doppler ultrasound of
another patient showns a vascularized expansive portal vein thrombus (arrows) and an
heterogeneous liver.

Page 5 of 17
Fig. 3: Same patient as in fig. 2. CT images, non enhanced (A), postcontrast arterial
phase (B) and portal venous phase (C,D). Tumor portal vein thrombus enhances in a
diffuse heterogeneous fashion (arrows, B,D). Heterogeneous enhanced ill defined area
is seen in right hepatic lobe superior segments (circle, C).

Fig. 4: Small infiltrative difuse-type HCC. MRI, T2 fat-suppressed turbo spin echo (TSE)
(A); T1 post-gadolinium spoiled gradient echo (SGE) arterial phase (B), portal venous
phase (C) and intersticial phase (D). Ill-defined lesion on hepatic segment IV (arrows and
circle) with intermediate signal intensity on T2 image and heterogeneous post-gadolinium
enhancement.

Page 6 of 17
Results

All patients presented with chronic liver disease, which etiologic distribution is shown in
figures 1 and 2.

Fifty percent only of the patients were included in the screening program for HCC
detection, based on ultrasound and AFP dosages in intervals of 4 to 6 months.

Ultrasound has missed infiltrative HCC detection in 10/20 patients (50%) while CT has
missed in 2/20 patients (10%). All 18 patients studied by MRI were diagnosed for
infiltrative HCC.

Four patients were classified as small infiltrative diffuse-type HCC, which represented
15.3% of diffuse-type HCC, and 2.2 % of all patients with HCC.

Mean serum AFP level was 1451.9 ng/ml, varying from 12.46 to 3630 ng/ml. Only six
patients (23%) presented with AFP lower than 200 ng/ml in the period close to the
diagnostic confirmation (12.46; 16.46; 31.34; 32.19; 52.39 and 143.99 ng/ml). There
was no difference of AFP levels between small infiltrative and diffuse disseminated HCC
groups (P = 0.71).

Mortality rate for diffuse disseminated HCC group was 72.7%, while for small infiltrative
diffuse HCC was 0%. The time interval average from the diagnose to death was 60 days
+/- 71, varying from 6 to 220 days.

Images for this section:

Page 7 of 17
Fig. 1

Page 8 of 17
Fig. 2

Page 9 of 17
Conclusion

1. Diffuse-type HCC imaging, clinical and laboratory findings in our study were similar to
those described in the literature [1,3].

2. Despite the fact that ultrasound is the method used in the majority of HCC screening
programs, its accuracy for the diffuse-type HCC is lower when compared with published
data on solitary and multifocal HCC types [7]. This can lead to a delayed diagnosis and
worse prognosis.

3. Identification of vascularized expansive portal vein thrombosis in patients with diffuse

liver disease with no defined hepatic mass lesion should indicate the possibility of diffuse-
type of HCC (fig. 1,2,3).

4. MR imaging with dynamic postcontrast technique is the most accurate method for
detection and characterization of the diffuse type HCC [3] (fig. 4).

5. Small infiltrative HCC type seems to have a better prognosis compared to disseminated
HCC type, although further studies are needed to confirm this finding.

6. Diffuse type HCC diagnosis remains a challenge for all imaging methods. It is also a
well-known cause of delayed HCC diagnosis in surveillance protocols of chronic hepatic
disease patients. Recognition of diverse imaging features of this tumor is paramount to
make an earlier diagnosis. Small infiltrative HCC is a rare and distinct presentation of
diffuse-type HCC and can be diagnosed by MRI.

Images for this section:

Page 10 of 17
Fig. 1: Color Doppler ultrasound showns an hypoechogenic vascularized expansive
portal vein thrombus (arrows). An heterogeneous liver without any defined mass is also
noted.

Fig. 2: Same patient as in fig. 1. Diffuse-type HCC with portal vein thrombosis. MRI,
T2 fat-suppressed TSE (A); T1 fat-suppressed SGE non enhanced (B), post-gadolinium
arterial phase (C) and portal venous phase (D). These images confirm the expansive

Page 11 of 17
portal vein thrombosis (arrows), which enhances in early phase post-gadolinium series.
There is an extensive ill-defined liver lesion involving the entire right lobe and partially the
left lobe, with a patchy enhancement pattern in early phase post-gadolinium image (C).
The portal venous phase image showns tumor as areas of multiple foci of wash-out (D).

Fig. 3: Diffuse-type HCC with portal vein thrombosis in a patient with hemochromatosis.
MRI, coronal T2 TSE (A), coronal T1 fat-suppressed SGE (B), axial T2 fat-suppressed
TSE (C), axial T1 SGE non enhanced (D), and post-gadolinium arterial phase (E), porta
venous phase (F) and fat-suppressed intersticial phase (G). Non-marginated lesion in the
right hepatic lobe, also associated with an extensive tumor thrombus in portal vein and
its branches. Miliary enhancement pattern of the lesion is noticed in the post-gadolinium
dynamic series, and a heterogeneous enhancement of the tumor thrombus. Liver showns
low signal intensity in all images due to hemochromatosis.

Page 12 of 17
Fig. 4: Diffuse-type HCC with portal vein thrombosis. CT images, axial non enhanced (A),
post-contrast dynamic series (B,C,D); MRI, axial T2 fat-suppressed TSE (E), T1 SGE in-
phase (F), T1 SGE post-gadolinium arterial phase (G), intersticial phase (H,I), coronal T2
TSE (J), T1 SGE (K) and T1 fat-suppressed intersticial phase (L). Extensive lesion with
ill defined margins involving the left and caudate lobes, associated with tumor portal vein
thrombosis. Post-gadolinium dynamic series shown patchy enhancement of the lesion
(circle) and tumor thrombus (arrows). There is no distinct margination of the lesion in
any image.

Page 13 of 17
References

1. Semelka RC, Voultsinos V, Altun E, Elias Junior, J. MRI of Focal Lesions in Normal
and Chronically Diseased Liver. In: Vincent B. Ho; Mark J. Kransdorf; Caroline Reinhold.
(Org.). Body MRI - Categorical Course Syllabus. Leesburg, VA: American Roentgen Ray
Society, 2006, v. , p. 11-38.

2. Franca AV, Elias Junior J, Lima BL, Martinelli AL, Carrilho FJ. Diagnosis, staging and
treatment of hepatocellular carcinoma. Braz J Med Biol Res 2004; 37:1689-1705.

3. Kanematsu M, Semelka RC, Leonardou P, Mastropasqua M, Lee JK. Hepatocellular

carcinoma of diffuse type: MR imaging findings and clinical manifestations. J Magn Reson
Imaging 2003; 18:189-195.

4. Okuda K, Noguchi T, Kubo Y, Shimokawa Y, Kojiro M, Nakashima T. A clinical and

pathological study of diffuse type hepatocellular carcinoma. Liver 1981; 1:280-289.

5. Livraghi T, Sangalli G, Giordano F, et al. 240 hepatocellular carcinomas: ultrasound

features, tumor size, cytologic and histologic patterns, serum alpha-fetoprotein and HBs
Ag. Tumori 1987; 73:507-512.

6. Kim YK, Han YM, Kim CS. Comparison of diffuse hepatocellular carcinoma and
intrahepatic cholangiocarcinoma using sequentially acquired gadolinium-enhanced and
Resovist-enhanced MRI. Eur J Radiol 2008.

7. Myung SJ, Yoon JH, Kim KM, et al. Diffuse infiltrative hepatocellular
carcinomas in a hepatitis B-endemic area: diagnostic and therapeutic impediments.
Hepatogastroenterology 2006; 53:266-270.

Personal Information

Jorge Elias Jr, MD, PhD.

Assistant Radiology Professor

Page 14 of 17
Head of Imaging Center of School of Medicine of Ribeirao Preto - University of Sao Paulo

jejunior@fmrp.usp.br

Mateus de Andrade Hernandes, MD.

Radiology Resident

PGY-3

mateusah@yahoo.com.br

Centro de Ciências das Imagens e Física Médica

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de

São Paulo

Av. Bandeirantes, 3.900 - Campus Universitário - Monte Alegre - 14.048-900 - Ribeirão

Preto - SP - Brazil

Images for this section:

Page 15 of 17
Fig. 1: School of Medicine of Ribeirao Preto shield and Imaging Center logo.

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