A 64-year-old man began treatment for chronic hepatitis C with peg-interferon and ribavirin. His hepatitis C virus ribonucleic acid (HCV-RNA) results turned negative. Just after the treatment, a computed tomography (CT) scan revealed a hypovascular mass in the segment 8. We performed a right hemihepatectomy as HCC. Upon macroscopic examination, the tumour was yellow and firm with a fibrous capsule. A wedge-shaped necrotic area was located at the top of an artery and a portal vein of segment 8. Necrosis was observed not only in the tumour but in the adjacent parenchyma. A histopathological examination showed that the tumour had been completely replaced by necrosis. This tumour was surrounded by capillary vessels and fed by several thick arteries, but organized thrombi were not detected. No viable cells were found. The histopathological diagnosis was a spontaneous complete necrosis of HCC caused by the occlusion of feeding vessels outside the capsule

Amemiya, Takeshi

Arai, Toshiyuki

Goto, Hidenari

Hiramatsu, Kiyoshi

Saeki, Satomi

Seki, Takashi

Tanaka, Hiroshi

English

Atharva Scientific Publications (E-Jounals)

Tanaka et al                            Spontaneous necrosis of hepatocellular carcinoma 
Vol 3 Issue 2 Apr – Jun 2017                                                        Indian J Case Reports / 54 
Case Report 
Spontaneous complete necrosis of hepatocellular carcinoma caused by 
feeding vessel occlusion outside the tumour capsule 
Hiroshi Tanaka, Satomi Saeki, Kiyoshi Hiramatsu, Takeshi Amemiya, Hidenari Goto, Takashi 
Seki, Toshiyuki Arai 
From, the Department of, Surgery, Anjo Kosei Hospital, Japan. 
Correspondence to: Dr Hiroshi Tanaka, Division of Surgical Oncology, Nagoya University Graduate School of Medicine, 65 
Tsurumai-cho, Showa-ku, Nagoya, Aichi, Japan 466-8550. Email: h-tanaka@med.nagoya-u.ac.jp 
Received: 20 Feb 2017    Initial Review: 10 Mar 2017    Accepted: 20 Mar 2017         Published Online: 25 Apr 2017 
ABSTRACT 
A 64-year-old man began treatment for chronic hepatitis C with peg-interferon and ribavirin. His hepatitis C virus ribonucleic 
acid (HCV-RNA) results turned negative. Just after the treatment, a computed tomography (CT) scan revealed a hypovascular 
mass in the segment 8. We performed a right hemihepatectomy as HCC. Upon macroscopic examination, the tumour was 
yellow and firm with a fibrous capsule. A wedge-shaped necrotic area was located at the top of an artery and a portal vein of 
segment 8. Necrosis was observed not only in the tumour but in the adjacent parenchyma. A histopathological examination 
showed that the tumour had been completely replaced by necrosis. This tumour was surrounded by capillary vessels and fed by 
several thick arteries, but organized thrombi were not detected. No viable cells were found. The histopathological diagnosis 
was a spontaneous complete necrosis of HCC caused by the occlusion of feeding vessels outside the capsule. 
Keywords: Spontaneous Necrosis, Hepatocellular Carcinoma, Vascular Occlusion. 
 
pontaneous necrosis or regression of neoplasms 
occurs in 1 in 60,000 to 100,000 of all tumours [1]. 
The spontaneous complete necrosis of 
hepatocellular carcinoma (HCC) is quite rare, with a 
frequengy of 1 in 140,000 cases of HCC [2]. Possible 
causes of necrosis include feeding vessels thrombosis, 
oxygen deprivation due to bleeding, and cessation of 
exposure to noxious agents, such as alcohol and tobacco 
smoke [3]. HCCs are generally fed only by the hepatic 
artery; hence, they shrink easily due to ischemia included 
by degreased arterial blood flow. In contrast, some 
immunological mechanisms, such as lymphocyte 
infiltration and various cytokines are related to the 
spontaneous necrosis of HCC [3-7]. However, the 
mechanism of the spontaneous necrosis and regression of 
HCC remains unclear.  
 
Here, we report the spontaneous complete necrosis of 
HCC by feeding artery or portal venous occlusion, as 
demonstrated by a histological examination. 
CASE REPORT 
A 64-years-old man began treatment for chronic 
hepatitis C with peg-interferon and ribavirin in October 
2011. His blood hepatitis C virus ribonucleic acid (HCV-
RNA) level decreased to below the measurable range 12 
weeks later. After the interruption of treatment 53 weeks 
later due to pancytopenia, an abdominal computed 
tomography (CT) scan revealed a tumour in the liver. The 
serum concentrations of proteins induced by vitamin K 
absence or antagonism-2 (PIVKA-2) and that of alpha-
fetoprotein (AFP) were not elevated, but that of cancer 
S 
Tanaka et al                            Spontaneous necrosis of hepatocellular carcinoma 
Vol 3 Issue 2 Apr – Jun 2017                                                        Indian J Case Reports / 55 
antigen 19-9 (CA19-9) was slightly elevated (43 IU/ml). 
The patient was referred to our hospital for surgery. 
A dynamically enhanced multi-detector-row CT 
(MDCT) images revealed a hypovascular mass measuring 
41 mm in the segment 8 of liver. An arterial phase image 
showed a capsule-like enhancement around the mass. This 
enhancement was unremarkable and continued in the 
delayed phase without wash-out. The inside of the mass 
took in little material, but slight intake by the intratumoral 
nodule appeared in the delayed phase (Fig. 1). Gadolinium 
ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-
EOB-DTPA) - enhanced magnetic resonance imaging 
(MRI) showed that the mass structure was more 
remarkable than that demonstrated by the CT scan, with a 
thick capsule and internal nodule. In contrast to the CT 
findings, the capsule and nodule were slightly enhanced 
from the early phase to the delayed phase. In the 
hepatocyte phase, the triangular enhancement of the 
parenchyma around the mass was absent (Fig. 2). 
 
Figure 1: Dynamically enhanced MDCT image A) Arterial 
phase, B) portal phase, and C) delayed phase. A 
hypovascular mass was present in the anterior segment. A 
capsule-like enhancement around the mass continued 
from the arterial phase to the delayed phase. Slight intake 
by an intratumoral nodule appeared in the delayed phase 
(yellow arrows). 
 
Figure 2: Gd-EOB-DTPA-enhanced MRI image of 
hepatocyte phase A) Axial and B) coronal images. The 
thick capsule and internal nodule were more remarkable 
than shown by CT and continually enhanced. The 
enhancement of the parenchyma around the mass was 
absent in triangular shape. 
We diagnosed the lesion as HCC or a combined 
hepatocellular and cholangiocarcinoma lesion due to the 
imaging findings and the patient’s history of hepatitis C. 
We performed a right hemihepatectomy in December 2012 
(operation time 465 min. blood loss 6536 ml). The patient 
was discharged on the 20th day after the operation. No 
recurrence was detected at 30 months after the operation. 
Upon macroscopic examination, the tumour was 
yellow and firm with a fibrous capsule. The wedge-shaped 
necrotic area was located at the top of an artery and a 
portal vein that fed the tumour and segment 8. These 
vessels were approximately 2 cm away from the HCC 
capsule. Necrosis was observed not only in HCC itself, but 
also in the adjacent parenchyma (Fig. 3). The histo-
pathological examination showed that the tumour in the 
cirrhotic liver had been completely replaced by central 
coagulative necrosis, which consisted of linearly-arranged 
large cells, similar to hepatocytes, and a few inflammatory 
cells. This coagulative necrosis was found not only in this 
tumour, but also in adjacent regenerative nodules. This 
tumour was surrounded by capillary vessels and was fed 
by several thick arteries, but no organised thrombi or 
Tanaka et al                            Spontaneous necrosis of hepatocellular carcinoma 
Vol 3 Issue 2 Apr – Jun 2017                                                        Indian J Case Reports / 56 
tumour cells in the hepatic artery were detected. No viable 
cells were found in this tumour (Fig. 4). The 
histopathological diagnosis was a spontaneous complete 
necrosis of HCC, possibly caused by the occlusion of 
feeding vessels outside the capsule. 
DISCUSSION 
The spontaneous regression of cancer is defined as the 
partial or complete disappearance of a malignant tumour in 
absence of all treatments or in presence of a therapy that is 
considered inadequate to exert a significant influence on 
neoplastic disease [8]. According to a report by Huz et al. 
in 2012 that reviewed 75 studies on spontaneous HCC 
regressions published in the English language, the 
common mechanisms of spontaneous regression of HCC 
were tumour hypoxia (n=21, 28.0%), a systemic 
inflammatory response (n=25, 33.3%) and unknown 
causes (n=29, 38.7%) [9]. These authors also noted that 
hypoxia resulted not only from direct ischemia, such as 
arterial or portal obstruction, but also from hypoperfusion, 
such as hypotension associated with variceal bleeding. 
 
Figure 3: Macroscopic findings of the specimen A) 
Resected liver and B) cut side of the tumour. The tumour 
was yellow and firm with a fibrous capsule. The wedge-
shaped necrotic area was located at the top of vessels 
feeding the tumour and segment 8 (yellow arrow). 
Necrosis was observed not only in the tumour itself, but 
also in the adjacent parenchyma (white arrows). 
 
Figure 4: Histopathological examination A,B) 
Hematoxylin-Eosin stain, and C,D) Elastica van Gieson 
stain. A) The tumour covered by thick fibrous capsule 
(white arrows) had been completely replaced by central 
coagulative necrosis, B) which consisted of linearly-
arranged large cells similar to hepatocytes and a few 
inflammatory cells. C) This coagulative necrosis (black 
arrows) was found not only in this tumour, but also in 
adjacent regenerative nodules. D) This tumour was 
surrounded by several thick arteries, but organized 
thrombi in the hepatic artery were not detected. 
As most previous cases have suggested, during 
vascular occlusion, arteries feeding necrotic HCCs become 
markedly narrowed and obstructed at the point at which 
they penetrate HCC capsules. Thick fibrous capsules 
around HCC stop the blood supply, resulting in necrosis. 
Theses occlusions have also originated from a thick 
fibrous medial membrane or a hyaline thrombus in the 
arterial wall. However, the adjacent tissues outside the 
capsule were nearly intact. Therefore, the occlusion was 
considered to have occurred in the vessels penetrating the 
HCC capsule. 
In the present case, we found an unusual 
histopathological result of spontaneous necrosis of HCC. 
A wedge-shaped necrotic area was located at the top of an 
artery and a portal vein that fed the HCC and segment 8. 
These vessels were distant from the capsule, and necrosis 
was observed not only in the HCC itself, but also in the 
adjacent parenchyma. This finding suggests that the 
occlusion of the vessels could have occurred at this point, 
particularly at the feeding artery, as though transcatheter 
arterial or portal venous embolisation had been performed 
before the operation. However, no emboli, such as 
thrombi, were detected in the vessels. Neither HCCs nor 
Tanaka et al                            Spontaneous necrosis of hepatocellular carcinoma 
Vol 3 Issue 2 Apr – Jun 2017                                                        Indian J Case Reports / 57 
inflammatory cells had invaded these vessels. No reports 
exist that describe their similar histological findings.  
We believe that some type of vascular obstruction, 
such as a spasm, occured in the present case. Regarding 
the start of necrosis, it is reasonable that the HCC was 
already present when this patient was medicated for 
hepatitis C. Two possible causes exist for this speculation. 
One cause is the cessation of smoking. The patient stopped 
smoking immediately before hepatitis C treatment. 
Changes in a vasoactive substance, such as nicotine or 
nitrogen oxide, cause an arterial occlusion [5]. The other 
cause is the medication that was administered for chronic 
hepatitis C. The administration and interruption of peg-
interferon and ribavirin might have stimulated an 
immunoreaction in the patient’s liver to cause necrosis, 
despite no previous report mentioning this effect.  
Although surgical case reports of the spontaneous 
regression and necrosis of HCC are increasing in 
frequency, but the detailed mechanism of necrosis remains 
unclear. Most of these cases include a partial resection; 
thus, the discussion of histopathological findings including 
adjacent parenchyma, are insufficient. Additional case 
reports of anatomical hepatectomy with detailed 
histopathological findings, such as those of Tomino, 
Yokoyama and Lee [10-12], are needed to investigate this 
necrotic mechanism. 
CONCLUSION 
We observed a rare case of spontaneous necrosis of HCC 
with specific histopathological findings. Additional case 
reports of anatomical hepatectomy are needed to clarify 
this phenomenon. 
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How to cite this article: Tanaka H, Saeki S, Hiramatsu 
K, Amemiya T, Goto H, Seki T, Arai T, Spontaneous 
complete necrosis of hepatocellular carcinoma caused 
by feeding vessel occlusion outside the tumour capsule. 
Indian J Case Reports. 2017; 3(2): 54-57. 
Conflict of interest: None stated, Funding: Nil 


Spontaneous complete necrosis of hepatocellular carcinoma caused by feeding vessel occlusion outside the tumour capsule

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Spontaneous complete necrosis of hepatocellular carcinoma caused by feeding vessel occlusion outside the tumour capsule

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