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ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 1  |  Page : 248-252

Role of MRI in distinguishing intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma


1 Department of Diagnostic Radiology, Faculty of Medicine, National Liver Institute, Menoufia University, Menoufia, Egypt
2 Department of Diagnostic Radiology, National Liver Institute, Menoufia University, Menoufia, Egypt

Date of Submission19-Mar-2019
Date of Decision18-Apr-2019
Date of Acceptance27-Apr-2019
Date of Web Publication27-Mar-2021

Correspondence Address:
Walaa A. E. Sakr
Shebin El-Kom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_122_19

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  Abstract 


Objectives
To evaluate the role of MRI in the diagnosis of mass-forming intrahepatic cholangiocarcinoma (mICC), its enhancement pattern with contrast agent, and distinction from poorly differentiated hepatocellular carcinoma (pHCC).
Background
mICC is the second most common primary hepatobiliary tumor that is increasing in incidence. Imaging characteristics in mICC differ significantly, having overlapping imaging features with pHCC. Thus, it is important to differentiate mICC from pHCC.
Patients and methods
A retrospective MRI study was conducted on 15 patients with mICC and 15 patients with pHCC referred to MRI unit of the National Liver Institute, Menoufia University from June 2017 to January 2019. MRI were analyzed for tumor shape, intratumoral hemorrhage, fibrous capsule, T2 signal intensity, capsular retraction, intratumoral fat, biliary dilatation, vascular invasion, intraductal lesion, intrahepatic metastasis, restricted diffusion, and enhancement pattern after contrast injection. Associations between MRI features and tumor type were examined using the Fisher's exact and χ2 tests.
Results
Late enhancement was more common in mICC than pHCC (P < 0.001). T2 central hypointense area was more common in mICC versus HCC (P = 0.001). Capsular retraction was more common in mICC than HCC (P = 0.001). Biliary dilatation was more common in mICC than pHCC (P = 0.001). Fat component was more in pHCC than mICC (P = 0.01). Fibrous capsule was more common in pHCC than mICC (P = 0.002). Others parameters were not significant.
Conclusion
Biliary dilatation, central fibrosis, overlying capsular retraction, and late enhancement at 3 min with absence of fat and fibrous capsule appear to be the most important characteristics for mICC and help its differentiation from pHCC.

Keywords: Cholangiocarcinom, hepatocellular carcinoma, intrahepatic tumours, mass-forming cholangiocarcinoma,MRI


How to cite this article:
Ali ZA, Habib RM, Sakr WA. Role of MRI in distinguishing intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma. Menoufia Med J 2021;34:248-52

How to cite this URL:
Ali ZA, Habib RM, Sakr WA. Role of MRI in distinguishing intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma. Menoufia Med J [serial online] 2021 [cited 2021 Dec 4];34:248-52. Available from: http://www.mmj.eg.net/text.asp?2021/34/1/248/311989




  Introduction Top


Intrahepatic cholangiocarcinomas are primary liver cancer composed of carcinoma cells that resemble biliary epithelial cells surrounded by fibrous stroma of various degrees. The Japanese Liver Cancer Group has classified ICCs into three types: mass forming, periductal-infiltrative, and intraductal [1].

Mass-forming intrahepatic cholangiocarcinoma (mICC) is the most common (60% of all ICCs) [2]. It can show various imaging findings on dynamic computed tomography or MRI using extracellular contrast agent [3]. mICC usually appears as a homogenous low-attenuation mass with irregular peripheral enhancement and can be accompanied by capsular retraction, satellite nodules, and peripheral intrahepatic duct dilatation [4].

Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and it is the leading cause of death in patient with cirrhosis [5]. Poorly differentiated hepatocellular carcinoma (pHCC) can show hypovascularity or ring-like enhancement, which sometimes mimics features of mICC. Despite the similarity of imaging finding on the arterial phase, delayed washout of pHCC can enable its differentiation from mICC when the examination is performed using an extracellular contrast agent [1]. Some investigators have reported that central scar displayed on MRI in cholangiocarcinoma can be a reliable marker allowing cholangiocarcinoma to be distinguished from metastatic liver tumor [6].

In spite of their similarities in preoperative imaging, hepatic resection is the only curative option for mICC, whereas other treatments such as radiofrequency ablation and transcatheter chemoembolization can be alternative treatment options for pHCC. Thus, it is important to differentiate mICC from pHCC [1].

The aim of this study was to retrospectively determine the role of MRI in diagnosis of mICC, its enhancement pattern with contrast agent, and distinction from pHCC.


  Patients and methods Top


This study was retrospective conducted on 30 patients after taking their consent. The study was approved by the ethical committee of the hospital and patients gave an informed consent (15 patients were pathologically diagnosed to have mICC and 15 patients were pathologically diagnosed to have pHCC) referred to the MRI Unit of the National Liver Institute, Menoufia University, from June 2017 to January 2019 for pretherapeutic assessment. Clinical data were obtained on serum viral markers (hepatitis B and hepatitis C). Chronic liver disease or cirrhosis was documented in the medical or pathological reports.

All patients in this study had pathological reports of diagnosed mICC or pHCC, signs of fibrous capsule, and intratumoral fibrous desmoplasia evaluated and compared with MRI findings.

MRI protocol

MRI was performed for all patients using a superconducting magnet operating at 1.5 T with sensitivity-encoding body coil including axial in-phase and out-of phase T1-weighted gradient-echo image (chemical shift imaging), single-shot T2-weighted spin-echo image with or without fat suppression, and diffusion-weighted image (DWI), and apparent diffusion coefficient (ADC) maps were automatically generated on the operating console using all three images with b-factors of 0, 500, and 1000 s/mm and dynamic fat-suppressed T1-weighted image using Gadolinium contrast agent including native, late arterial (18–25 s), portal venous (55–60 s), and dynamic late phases (3 min) following the administration of gadolinium contrast. The contrast was administered as a bolus dose at a rate of 2 ml/s (0.025 mmol/kg body weight) through an intravenous cubital line (22 G) that was flushed with 20-ml saline using a power injector.

The MRI findings were evaluated for primary radiological diagnosis and then compared with pathological results to assess the role of MRI in diagnosis of intrahepatic mICC and distinction from pHCC.

Image evaluation

The MR morphological features of each lesion were recorded, including shape, signal characteristics, intraregional fat/hemorrhage, capsular retraction, biliary dilatation, vascular invasion, intrahepatic metastasis, and pattern of enhancement in the dynamic imaging. The results were compared and correlated with laboratory and histopathology results in all patients.

Intratumoral fat was identified by focal high signal in T1 in phase that dropped off in signal noted in T1 out of phase. Intratumoral hemorrhage was identified by T1 high signal intensity without signal drop in out phase/T2 low signal area. A fibrous capsule was identified by thin hypointense rim encircling the lesion on T2-weighted image with rim enhanced in dynamic late phase. The arterial enhancement pattern was classified as ring like or others, and late enhancement was defined as area of gradually increasing intensity on dynamic late phase. The DWI and ADC maP value of each tumor was measured by placing a region of interest on the ADC map.

Statistical analysis

The data collected were tabulated and analyzed by statistical package IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. for the social science software version 22 on IBM compatible computer.

Student t test

Quantitative data were expressed as mean and SD and analyzed by applying Student t test for comparison of two groups of normally distributed variables and Mann–Whitney U test for nonnormally distributed ones.

χ2 test

Qualitative data were expressed as number and percentage and analyzed by applying χ2 test. Whenever the expected values in one or more of the cells in a 2 × 2 tables were less than 5, Fisher's exact test and likelihood ratio were used instead. All these tests were used at the following level of significance: P value more than 0.05 not significant, P value less than 0.05 significant, and P value less than 0.01 highly significant.


  Results Top


[Table 1] shows MRI findings of patient characteristics. We observed a highly significant difference in patients with liver cirrhosis distribution between mICC and pHCC groups (P = 0.001); however, two of 15 cases also had liver cirrhosis even in mICC group. The two groups had no significant difference in age and sex.
Table 1: MRI findings of patient characteristics

Click here to view


Lobulated shaped masses were seen in nine (60%) mICC cases and three (15%) pHCC cases (P = 0.009). T2 central hypointense area was seen in seven (46.7%) mICC cases [Figure 1] and [Figure 2] and one (6.7%) pHCC case (P = 0.001). Overlying capsular retraction was seen in seven (46.7%) mICC cases [Figure 1] and [Figure 2] and none (0%) of pHCC cases (P = 0.001). Biliary dilatation was seen in all mICC cases (100%) [Figure 1] and [Figure 2] and two (13.3%) pHCC cases [Figure 3] (P = 0.001). Fibrous capsule was seen in six (40%) pHCC cases [Figure 3] and none (0%) of mICC cases (P = 0.002). Intralesional fat was seen in four (26.7%) pHCC cases [Figure 4] and none (0%) of mICC cases (P = 0.01). Vascular invasion was seen in four (26.6%) of pHCC cases and none (0%) of mICC cases (P = 0.013). Progressive enhancement in delayed phase was seen in all mICC cases (100%) [Figure 1] and [Figure 2] and none of pHCC (0%) (P = 0.001). Contrast washout in delayed phase was seen in all pHCC cases (100%) [Figure 3], and [Figure 4] and none (0%) of mICC cases (P = 0.001). No significant difference was observed in terms of intratumoral hemorrhage, intraductal lesion, intrahepatic metastasis, lymph nodes metastasis, or ADC value.
Figure 1: (a–e) A 56-year-old male patient with left hepatic lobe sizable lobulated mass with restricted diffusion shows high signal intensity in DWI (a) and low signal in ADC (b), T2 central low signal area with overlying capsular retraction and peripheral biliary dilatation (c), and peripheral arterial enhancement (d) with progressive enhancement at delayed phase (e). He was pathologically diagnosed as having mICC. ADC, apparent diffusion coefficient; DWI, diffusion-weighted image; mICC, mass-forming intrahepatic cholangiocarcinoma.

Click here to view
Figure 2: (a–d) A 60-year-old female patient with right hepatic lobe sizable mass shows restricted diffusion in DWI (a), T2 central low signal area with minimal peripheral biliary dilatation (b), and peripheral arterial enhancement (c) with progressive enhancement at delayed phase (d). She was pathologically diagnosed as having mICC. DWI, diffusion-weighted image; mICC, mass-forming intrahepatic cholangiocarcinoma.

Click here to view
Figure 3: (a–d) A 62-year-old male patient with right hepatic lobe lobulated mass with restricted diffusion in DWI (a), with T2 high signal with internal hemorrhage of area of low signal and mild biliary dilatation (b), showing arterial enhancement (c) with washout in delayed phase (d). He was pathologically diagnosed as having HCC. DWI, diffusion-weighted image; HCC, hepatocellular carcinoma.

Click here to view
Figure 4: (a–d) A 54-year-old male patient with liver cirrhosis. Axial T1 in-phase (a) and out-of-phase (b) image shows right hepatic lobe multifocal iso signal masses with rim of low signal of fibrous capsule; one of this lesion at segment intravenous shows signal drop in out phase (b), denoting intralesional fat. All lesions show arterial enhancement (c) with washout in delayed phase (d). Pathologically diagnosed as having multicentric HCC. HCC, hepatocellular carcinoma.

Click here to view



  Discussion Top


In this study, MRI revealed interesting differences between mICC and pHCC, particularly relating to the presence of biliary radicles dilatation, capsular retraction, intratumoral fat, and late enhancement at three minutes after contrast agent injection.

In the current study, there was a significant difference in lobulated shape of mICC in nine of 15 cases, which agreed with Chung et al. [4], who found that at gross examination, mICC is characterized by a homogeneous sclerotic mass with an irregular lobulated margin. This is also in agreement with Park et al. [7] who found that mICC frequently appeared as an ill-defined lobulated mass, which differentiated from the sharp and round shape of classic HCC.

In our study, there was a significant difference in central hypointense area on T2-weighted image seen in seven of 15 (46.6%) cases of mICC, which is concordant with Péporté et al. [6] who observed central hypointensity on T2-weighted image in 27 (54%) of 50 cases of mICC and suggested internal desmoplastic changes, reflecting severe fibrosis.

In this study, most of HCC cases had high signal in T2-weighted image, with highly significant difference, which disagrees with Watanabe et al. [8] who noted that HCCs tend to show minimal to mildly increased signal intensity on T2weighted images, as opposed to intrahepatic cholangiocarcinoma or mixed HCC-cholangiocarcinoma.

In the current study, there was a highly significant difference regarding the capsular retraction for mICC seen in seven (46.36%) of 15 cases, which agrees with Chung et al. [4] who found that the capsular retraction may be seen in some HCCs with cirrhotic stroma but is more suggestive of mICC. Moreover, the results agree with Da Ines et al. [9] who found that capsular hepatic retraction is observed in 20% of cholangiocarcinoma.

This finding was against the study done by Zhao et al. [10] who found no significant difference regarding capsular retraction in comparison between patients with mICC and those with HCC.

In this study, there was a highly significant difference in association of biliary dilatation in patients with mICC, which agrees with Ringe and Wacker [11] who noted secondary signs are more commonly associated with mICC, including bile duct dilation distal to the tumor.

In our study, there was a highly significant difference of progressive central enhancement in delayed phase in patients with mICC in comparison with patients with pHCC, which agrees with Ringe and Wacker [11], who stated that the classic enhancement pattern of mICC is heterogeneous or homogeneous with progressive and prolonged delayed enhancement; moreover, it agrees with Chung et al. [4] who stated that both the peripheral and the centripetal enhancement of mICC may be more prominent at MRI than at computed tomography.

This finding was against the study done by Kim et al. [12] who reported that 4.3% of mICC showed arterial enhancement with washout during portal venous phase.

In this study, there was significant difference of liver cirrhosis and vascular invasion in patients with pHCC in comparison with patients with mICC. This finding agrees with Arif-Tiwari et al. [13] who support that HCC is a disease mostly observed in chronic liver disease and also found that vascular invasion by HCC is a common feature that is observed microscopically and is identified on a subset of cases on MRI.

In the current study, fatty changes in pHCC were significant finding in four (26.6%) of 15 cases, which is concordant with Siripongsakun et al. [14] who found that intratumoral fat is an important diagnostic clue for HCC.

In the current study, there was a significant difference regarding fibrous capsule of pHCC cases, which agrees with Asayama et al. [1] who stated that the absence of fat and fibrous capsule and presence of enhancement at 3 min are more indications of mICC than pHCC.

In this study, there was no significant difference regarding DWI and ADC value for differentiating ICC and HCC, which agrees with Nishie et al. [15] who deduced that it is difficult to differentiate mICC from pHCC by means of ADC.

Points of strength

All patients in this study had pathological reports of mICC or pHCC that could be compared with MRI findings.

Points of weakness

There were limited number of mICC cases during the period of the study. Some patients with mICC were excluded from the study as they had only magnetic resonance cholangiopancreatography without dynamic imaging.


  Conclusion Top


Intrahepatic lobulated mass surrounded by biliary radicles dilatation with central fibrosis, overlying capsular retraction, and late enhancement at 3 min with absence of fat and fibrous capsule appear to be most characteristic for mICC and help its differentiation from pHCC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Asayama Y, Nishie A, Ishigami K, Ushijima Y, Takayama Y, Fujita N, et al. Distinguishing intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma using precontrast and gadoxetic acid-enhanced MRI. Diagn Interv Radiol 2015; 21:96–104.  Back to cited text no. 1
    
2.
Seo N, Kim DY, Choi JY. Cross-sectional imaging of intrahepatic cholangiocarcinoma: development, growth, spread, and prognosis. Am J Roentgenol 2017; 209:64–75.  Back to cited text no. 2
    
3.
Asayama Y, Yoshimitsu K, Irie H, Tajima T, Nishie A, Hirakawa M, et al. Delayed-phase dynamic CT enhancement as a prognostic factor for mass-forming intrahepatic cholangiocarcinoma. Radiology 2006; 238:150–155.  Back to cited text no. 3
    
4.
Chung YE, Kim MJ, Park YN, Choi JY, Pyo JY, Kim YC, et al. Varying appearances of cholangiocarcinoma: radiologic-pathologic correlation. Radiographics 2009; 29:683–700.  Back to cited text no. 4
    
5.
Media M, Orlando E, Camma C, Cabibbo G. Staging system of hepatocellular carcinoma: a review of literature. World J Gastroenterol 2014; 20:4141–4150.  Back to cited text no. 5
    
6.
Péporté AR, Sommer, WH, Nikolaou K, Reiser MF, Zech CJ. Imaging features of intrahepatic cholangiocarcinoma in Gd-EOB-DTPA-enhanced MRI. Eur J Radiol 2013; 82:101–106.  Back to cited text no. 6
    
7.
Park HJ, Kim YK, Park MJ, Lee WJ. Small intrahepatic mass-forming cholangiocarcinoma: target sign on diffusion-weighted imaging for differentiation from hepatocellular carcinoma. Abdom Imaging 2013; 38:793–801.  Back to cited text no. 7
    
8.
Watanabe A, Ramalho M, AlObaidy M, Kim HJ, Velloni FG, Semelka RC. Magnetic resonance imaging of the cirrhotic liver: An update. World J Hepatol 2015; 7:468–487.  Back to cited text no. 8
    
9.
Da Ines D, Mons A, Braidy C, Montoriol PF, Garcier JM, Vilgrain V. Hepatic capsular retraction: spectrum of diagnosis at MRI. Acta Radiol Short Rep 2014; 3:1–10.  Back to cited text no. 9
    
10.
Zhao YJ, Chen WX, Wu DS, Zhang WY, Zheng LR. Differentiation of mass-forming intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma: based on the multivariate analysis of contrast-enhanced computed tomography findings. Abdom Radiol 2016; 41:978–989.  Back to cited text no. 10
    
11.
Ringe KI, Wacker F. Radiological diagnosis in cholangiocarcinoma: application of computed tomography, magnetic resonance imaging, and positron emission tomography. Best Pract Res Clin Gastroenterol 2015; 29:253–265.  Back to cited text no. 11
    
12.
Kim SA, Lee JM, Lee KB, Kim SH, Yoon SH, Han JK, et al. Intrahepatic mass-forming cholangiocarcinomas: enhancement patterns at multiphasic CT, with special emphasis on arterial enhancement pattern—correlation with clinicopathologic findings. Radiology 2011; 260:148–157.  Back to cited text no. 12
    
13.
Arif-Tiwari H, Kalb B, Chundru S, Sharma P, Costello J, Guessner RW, et al. MRI of hepatocellular carcinoma: an update of current practices. Diagn Interv Radiol 2014; 20:209–222.  Back to cited text no. 13
    
14.
Siripongsakun S, Lee JK, Raman SS, Tong MJ, Sayre J, Lu D. MRI detection of intratumoral fat in hepatocellular carcinoma: potential biomarker for a more favorable prognosis. Am J Roentgenol 2012; 199:1018–1025.  Back to cited text no. 14
    
15.
Nishie A, Tajima T, Asayama Y, Ishigami K, Kakihara D, Nakayama T, et al. Diagnostic performance of apparent diffusion coefficient for predicting histological grade of hepatocellular carcinoma. Eur J Radiol 2011; 80:29–33.  Back to cited text no. 15
    


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