Fibrolamellar hepatocellular carcinoma (fHCC) is a distinct type of first time used hence- hepatocellular carcinoma affecting particularly young patient with no gender predilection. However, there is increasing evidence of occurrence of this tumor in elderly patients also. Abdominal imaging with pre-operative biopsy provides accurate diagnosis. However, in difficult situations, CD68, cytokeratin 7, HepPar1, etc., immunohistochemical stains provide accurate diagnosis to differentiate this condition from other malignancies. Hereby, we present a case of fHCC in a 55-year-old female with equivocal imaging features and diagnosis was made by histopathology aided by immunohistochemistry

Agrawal, Nikhil

Chaudhari, Sachin

Rastogi, Archana

Taneja, Kanika

Thapar, Shalini

English

Atharva Scientific Publications (E-Jounals)

Vol 4 | Issue 1 | Jan - Feb 2018 Indian J Case Reports 31
Case Report
Unusual presentation of fibrolamellar carcinoma: A rare case report
Sachin Chaudhari1, Archana Rastogi1, Kanika Taneja1, Shalini Thapar2, Nikhil Agrawal3
From 1Departments of Pathology, 2Radio Diagnosis, 3Hepatobiliary Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
Correspondence to: Dr. Archana Rastogi, Department of Pathology, Institute of Liver and Biliary Sciences, D1, VasantKunj, 
New Delhi - 110070, India. Phone: +91-9540950901. E-mail: drarchanarastogi@gmail.com
Received - 27 September 2017 Initial Review - 21 October 2017 Published Online - 17 December 2017
Fibrolamellar hepatocellular carcinoma (fHCC) is recognized as separate hepatic carcinoma in the WHO 2010 classification of tumors of gastrointestinal system [1]. 
This tumor particularly affects young age group with no sex 
predilection and lacks background liver disease [2]. Bimodal age 
distribution of fHCC is recently described [3]. Histopathology 
shows large polygonal cells arranged in the stroma composed 
of lamellar fibrosis. Few cells are eosinophilic due to prominent 
mitochondria [1]. Various immunohistochemistry (IHC) markers 
such as CD68, cytokeratin 7 (CK7), HepPar1, and arginase when 
positive help in diagnosis of fHCC [4]. We present a case of fHCC 
in a 55-year-old female with unusual imaging features. Definite 
diagnosis was made by histopathology combined with IHC.
CASE REPORT
A 55-year-old female presented with abdominal pain for 2 months. 
Pain was dull aching and dragging type. It was not associated with 
fever, vomiting, constipation, or diarrhea. She had no significant 
family or family history. On abdominal examination, abdomen 
was slightly enlarged and mass was felt on palpation, but further 
examination cannot be done due to tenderness.
Ultrasound examination showed abdominal mass; hence, 
she was further evaluated. On routine liver function test, she 
had total bilirubin; 1 mg/dl, aspartate transaminase; 196 IU/L, 
alanine transaminase; 34 IU/L, alkaline phosphatase; 184 IU/L; 
and gamma-glutamyltranspeptidase of 51 IU/L. She had reversal 
of albumin/globulin ratio with albumin of 2.4 g/dl and globulin 
of 4.9 g/dl. Her serum immunoglobulin G was raised (20.6 g/l) 
and hepatitis C virus-RNA and hepatitis B surface antigen 
were negative. Magnetic resonance imaging (MRI) of whole 
abdomen revealed a large lobulated mass measuring 15.5 cm 
× 11 cm × 4 cm × 148 cm in the left subdiaphragmatic space 
with heterogeneous post-enhancement (Figs. 1 and 2). Fat planes 
between mass and stomach were lost. The mass was having a 
very small connection with liver. Liver showed irregular outline 
with relative hypertrophy of left and caudate lobe. Considering 
these, the possibility of malignant gastrointestinal tumor was 
kept. Further, the lesion was showing areas of hypervascularity 
in arterial phase in peripheral parts with evidence of central scar. 
In equilibrium and hepatobiliary phase, there was heterogeneous 
spoke wheel-like pattern of enhancement. Considering these 
features, the possibility of fHCC was kept which may have 
pedunculated from the left lobe. Thus, to differentiate the two 
possibilities, the patient was further investigated. Other serum 
investigations done further showed a carcinoembryonic antigen 
(CEA); 2.14 ng/ml (normal range 0–5 ng/ml), CA19.9; 29.7 U/ml 
(normal range 0–37 U/ml), and mildly raised AFP; 11.64 ng/ml 
(normal range 0–8.5 ng/ml).
Hence, for confirmation, the core biopsy of mass was done. 
Biopsy on low power showed the cells with moderate to abundant 
cytoplasm arranged in the form of sheets, cords, ill-defined acini, 
and few singly scattered cells. The stroma showed fibrosis and 
was relatively hypocellular. On high power, the polygonal cells 
with hepatocytes differentiation were seen. They had round 
to oval pleomorphic, hyperchromatic nuclei with prominent 
nucleoli. Few of them were showing intranuclear vacuoles. 
Cytoplasm was granular and eosinophilic to clear. The stroma 
showed parallel lamellated fibers of collagen with spindle cells 
entrapped in between them (Fig. 3a and b). Thus, the possibility 
of gastrointestinal stromal tumor was ruled out.
IHC was done to confirm the diagnosis. Tumor cells 
showed cytoplasmic positivity for arginase 1 and canalicular-
membranous immunostaining with polyclonal CEA indicating 
ABSTRACT
Fibrolamellar hepatocellular carcinoma (fHCC) is a distinct type of first time used hence- hepatocellular carcinoma affecting 
particularly young patient with no gender predilection. However, there is increasing evidence of occurrence of this tumor in elderly 
patients also. Abdominal imaging with pre-operative biopsy provides accurate diagnosis. However, in difficult situations, CD68, 
cytokeratin 7, HepPar1, etc., immunohistochemical stains provide accurate diagnosis to differentiate this condition from other 
malignancies. Hereby, we present a case of fHCC in a 55-year-old female with equivocal imaging features and diagnosis was made 
by histopathology aided by immunohistochemistry.
Key words: Arginase, CD68, Fibrolamellar hepatocellular carcinoma
Chaudhari et al. Fibrolamellar hepatocellular carcinoma
Vol 4 | Issue 1 | Jan - Feb 2018 Indian J Case Reports 32
hepatocytes differentiation [5-7]. Cytoplasmic positivity for 
CK7 was also present. IHC panel also included markers to 
exclude the differential diagnoses of combined hepatocellular-
cholangiocarcinoma (stem cell markers and CD117) and 
adrenocortical carcinoma (vimentin and inhibit) were 
performed [8,9]. Tumor cells showed cytoplasmic granular 
positivity for CD68, whereas CD117, vimentin, and inhibit were 
negative (Fig. 4a-d). Hence, the tumor was finally labeled as 
fHCC. Tissue from the adjacent liver was not received; hence, 
histological confirmation of the parenchymal liver disease was 
not possible. The tumor was not amenable to surgical resection 
due to loss of fat planes with stomach. Considering the spread 
of the tumor, the patient was given palliative treatment but 
succumbed to death after 2 months.
DISCUSSION
The fibrolamellar carcinoma usually occurs in the young patients 
with normal background liver and has no sex predilection. 
Our patient was 55-year-old female with evidence of chronic 
parenchymal disease on MRI. Recently, fHCCs are also known 
to occur in elderly patients, leading to bimodal age distribution 
of this tumor [10]. They express both hepatocyte and bile duct 
IHC markers such as CK7, HepPar1, polyclonal CEA, and 
arginase 1 [4]. Along with these markers, they also commonly 
express CD68 [1]. CD68 is a glycoprotein which is commonly 
found in lysosomes and endosomes. Tumor cells in fHCC are rich 
in these organelles; hence are positive for CD68 IHC [11].
The scirrhous HCC was considered in differential diagnosis 
because the tumor was showing positivity for CK7 and arginase 
and was negative for HepPar1. Furthermore, the tumor had 
fibrous stroma, but the lamellated appearance of stroma with 
positivity for CD68 confirmed the diagnosis of the fHCC [12]. 
Similarly, combined hepatocellular and cholangiocarcinoma 
and adrenocortical carcinoma were ruled out with IHC [8,9]. 
The fHCC has a specific gene mutation, DNAJB1-PRKACA 
fusion. Both these are located on chromosome number 13, and 
their fusion gene is responsible for upregulation of PRKARCA 
gene [13]. The PRKACA is subunit of serine/threonine kinase. 
This kinase has a lot of cellular targets including mitochondrial 
biogenesis [14]. Tumor cells of fHCC are known to have increased 
mitochondria; hence, few of them show dense eosinophilic or 
oncocytic cytoplasm [15]. Thus, there must be some relation 
between PRKACA and this morphology.
Chung et al. in their study have described MRI features of 
fHCC. They found tumor to show increased enhancement on 
T1-weighed images. Central scar is not enhancing in the arterial 
phase similar to the present case [16]. HCC growing outside liver 
is known as exophytic or pedunculated HCC. They are usually 
larger due to enough space for growth in abdominal cavity. They 
arise from right lobe, left lobe, and inferior hepatic rim in the 
descending order of their frequency [17]. There is rare case report 
Figure 1: Non-enhanced magnetic resonance imaging images of the tumor (a) coronal balanced steady state free precession sequence depicting 
the extent of the heterogeneous soft tissue mass in the left subdiaphragmatic location, abutting the left lobe of liver (red dotted outlines of 
tumor margins)with a central hyperintense scar(*) (b) T2-weighted axial sequence of the upper abdomen demonstrating small area in left 
lobe of liver, segment II (bold arrow) showing heterogeneity of signal in contiguity with the left subdiaphragmatic mass lesion (*) (c) diffusion 
weighted sequence (b value=1000) showing restriction of the segment of liver (bold arrow) and the restricted signal of the mass lesion (*)
a b c
Figure 2: Dynamic contrast-enhanced magnetic resonance imaging 
(CEMRI) of the liver with hepatocyte specific contrast (Gd-BOPTA) 
(a) T1-weighted non-enhanced axial sequence of upper abdomen 
showing hyper intense area (bold white arrow with black outline) 
within the mass lesion (*) suggestive of hemorrhage (b) T1-weighted 
CEMRI axial sequence in arterial phase of the upper abdomen 
demonstrating areas of hyper vascularity (white arrow) in the 
peripheral portion of the left subdiaphragmatic mass lesion (*) (c) 
T1-weighted CEMRI axial sequence in equilibrium phase showing 
heterogeneous spoke wheel pattern like enhancement (bold white 
arrow) of the mass lesion (*) (d) T1-weighted CEMRI axial sequence 
in hepatobiliary phase showing diffuse hypointense signal of the mass 
(*) with heterogeneous spoke wheel pattern and partly enhancing 
central scar (bold white arrow)
a
c
b
d
Chaudhari et al. Fibrolamellar hepatocellular carcinoma
Vol 4 | Issue 1 | Jan - Feb 2018 Indian J Case Reports 33
of diagnostic dilemma between pedunculated HCC and adrenal 
metastasis. The authors have stated that as the tumor enlarges it 
becomes increasingly difficult to distinguish between adrenal and 
hepatic origin [18]. However, our large tumor was presenting as 
left-sided subdiaphragmatic mass, so the possibility of adrenal 
origin was low. Furthermore, we ruled out this possibility with 
the help of IHC.
The scirrhous HCC can resemble fHCC on imaging as 
both show delayed contrast enhancement due to significant 
fibrous component. Further, as scirrhous carcinoma is located 
commonly in subcapsular location, so it may also lead to 
pedunculated appearance [12]. The delayed enhancement is 
also seen in other tumors with fibrous component such as 
intrahepatic cholangiocarcinoma and combined hepatocellular-
cholangiocarcinoma. Thus, there is often diagnostic dilemma 
on imaging due to fibrous component. Central scar with delayed 
enhancement is also seen in focal nodular hyperplasia [19]. 
Finally, pre-operative percutaneous biopsy helps in accurate 
diagnosis of the condition.
Prognosis of fHCC is similar to the classic HCC in normal 
liver background, and their specific clinical features are not 
responsible for the better prognosis of disease [20]. As compared 
to the classic HCC, they are relatively less chemosensitive; hence, 
surgery is the main modality of treatment. There is increased 
chance of lymph node and peritoneal metastasis than classic 
HCC; hence, these tumors are more prone to recur [1]. Adjacent 
liver was not sampled in the biopsy in this case; hence, the MRI 
findings could not be confirmed on histology. The liver function 
tests were considerably abnormal. Deranged tests can also be due 
to the secondary effects of tumor in normal liver. Thus, although 
MRI showed evidence of chronic parenchymal liver disease, this 
case is labeled as fHCC in view of typical histological and IHC 
profile.
CONCLUSION
The diagnostic dilemma of equivocal radiology features can be 
solved by histopathology and ancillary techniques in a case of 
suspected HCC. The fHCC diagnosis can be confidently given in 
biopsy sample when there is the presence of classic histological 
features with positive immunopanel composed of CD68, arginase 
or HepPar1, and CK7.
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Funding: None; Conflict of Interest: None Stated.
How to cite this article: Chaudhari S, Rastogi A, Taneja K, Thapar S, 
Agrawal N. Unusual presentation of fibrolamellar carcinoma: A rare case 
report. Indian J Case Reports. 2018;4(1):31-34.


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Unusual presentation of fibrolamellar carcinoma: A rare case report

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