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Hiroshi Hano,
Keisuke Nagatsuma, Tomoe Lu, Chenxi Meng, Satoru Chiba, Department
of Pathology, Jikei University School of Medicine, Tokyo, Japan
Ichiro Takagi, Department of Internal Medicine Division of
Gastroenterology and Hepatology, Jikei University School of Medicine,
Tokyo, Japan
Correspondence to: Dr. Hiroshi Hano, Department of Pathology,
Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku,
Tokyo 105-8461, Japan. hhano@jikei.ac.jp
Telephone: +81-3-34331111-2230 Fax: +81-3-54720700
Received: 2006-10-13
Accepted: 2006-12-18
Abstract
An 81-year-old Japanese man with jaundice was strongly suspected
clinically of having primary sclerosing cholangitis based on clinical
examinations and later died of hepatic failure. The entire course of the
disease lasted about 10 mo. The autopsy revealed extensive fibrinoid
necrosis in the liver, kidney, spleen, pancreas, lung, lymph nodes, and
pleura. Particularly extensive fibrinoid necrosis in the portal tracts
of the liver induced severe stenoses of the intrahepatic bile ducts,
resulting in cholestasis in association with prominent liver injury.
There were no findings indicating primary sclerosing cholangitis. The
hepatic lesions in this case did not coincide with any known disease
including collagen diseases. To clarify the cause of irregular stenoses
of the intrahepatic biliary trees on cholangiographic findings, we
postulate that some form of immunological derangement might be involved
in pathogenesis of fibrinoid necrosis. However, the true etiology
remains unknown.
© 2007 The WJG Press. All rights reserved.
Key words: Jaundice; Fibrinoid necrosis; Cholangio-graphy;
Primary sclerosing cholangitis; Liver; Autopsy
Hano H, Takagi I, Nagatsuma K, Lu T, Meng C, Chiba S. An autopsy case
showing massive fibrinoid necroses of the portal tracts of the liver
with cholangiographic findings similar to those of primary sclerosing
cholangitis. World J Gastroenterol 2007; 13(4): 639-642
http://www.wjgnet.com/1007-9327/13/639.asp
INTRODUCTION
We herein present an unusual autopsy case showing systemic fibrinoid
necroses in various organs. The case was strongly suspected clinically
of primary sclerosing cholangitis (PSC) based on the cholangiographic
findings; however, the autopsy disclosed systemic fibrinoid necroses
instead of histological features of PSC. Particularly noteworthy was the
presence of fibrinoid necrosis in the portal tracts of the liver caused
stenoses of the biliary trees in association with cholestasis. We could
not find any similar case reported in the literature. Presently, the
etiology remains unknown.
CASE REPORT
About 10 mo before admission to our hospital, an 81-year-old Japanese
man was admitted to a local hospital because of jaundice. Laboratory
examinations revealed elevated levels of serum total bilirubin and other
serum enzymes such as alkaline phosphatase, γ-glutamyltranspeptidase,
leucine aminopeptidase. Serum autoantibodies such as anti nuclear
antibody, anti mitochondrial antibody and anti smooth muscle antibody
were negative. Endoscopical retrograde cholangiogram showed
characteristic irregularity and beading of the intrahepatic biliary tree
(Figure 1).
No extrahepatic involvement was found. The patient was strongly
suspected clinically of PSC. The pathologic diagnosis of the liver
biopsy specimen was liver damage with cholestasis. Concentric fibrosis
around the bile ducts suggesting PSC was not found. The patient was
transferred to our hospital 18 d before death because of aggravation of
jaundice, anorexia and easy fatigability. Chronological laboratory data
is shown in
Table 1. Serum fibrinogen was within normal lower limit.
Plasminogen and D-dimer in serum were not examined. Serologic markers
for hepatits B and C viral hepatitis were negative. These findings
indicated that the liver cell damage rapidly worsened with aggravation
of cholestasis, especially in end stage. Despite symptomatic and
supportive treatment, the jaundice became progressively worse, and
ascites and hepatic encephalopathy developed. The patient eventually
died of hepatic failure.
An autopsy was performed about two hours after his death. The
diagnoses at autopsy except for systemic fibrinoid necrosis were
cholestatic liver damage, acute renal swelling, acute pancreatitis, mild
cardiac hypertrophy
(350 g) and latent adenocarcinoma of the prostate. Pathologic findings
concerning fibrinoid necrosis are described as follows.
The liver (1380 g) showed a deeply yellow-brown cut-surface due to
cholestasis with scattered simple small cysts. Gross examination could
not detect remarkable changes of the common bile duct and bilateral
hepatic ducts. Microscopically the most striking feature was a massive
deposition of homogeneous material stained scarlet with Masson's
trichrome in the portal tracts (Figure
2). Careful examinations disclosed that the material was
deposited in the walls of arteries and portal veins as well as in the
connective tissue (Figure
3). In the bile ducts the deposits circumscribed the lumen
leaving the epithelial lining intact and caused marked stenosis. The
area of the involved vessels and ducts extended from the distal
interlobular portion to the proximal septal portion (Figures 2 and 3).
The material was stained violet with PTAH and immunohistochemically was
positive for fibrinogen and negative for immunoglobulins such as IgG,
IgM, and IgA, C3 and C1q (Figure
4A). Electron microscopic findings of the liver were electron
dense materials deposited in the involved tissue (Figure
4B). The results of these stainings and electronmicrogram
suggested that the lesion with homogeneous material deposition was
fibrinoid necrosis. In addition, the portal tracts were enlarged and
infiltrated with lymphocytes and plasma cells with an occasional
intermingling of polymorphonuclear cells, ductular proliferation and
fibrosis. The histologic features were biliary interface activity,
resulting from cholestasis. However, it was noted that the lesion with
fibrinoid necrosis was scarcely accompanied by inflammatory reactions.
Cholestasis also caused conspicuous paren-chymal damage including
feathery degeneration or necrosis. Although the liver was extensively
examined histologically, there were no detectable features of PSC.
The kidney (250 g, respectively) showed marked swelling. Histologically
fresh fibrinoid necrosis was found in various degrees mainly in the wall
of the interlobular arteries (Figure
5). However, it was not accompanied by any inflammatory
reaction. Elastica-Van Gieson stain also demonstrated the destructive
changes of the arterial walls suggestive of old vascular lesions.
Occasionally, focal fibrinoid necrosis involved tubules and connective
tissue.
Intensive fibrinoid necrosis was noticed in lymph nodes and
the spleen. Old vascular lesions were also found frequently in the
spleen. The pancreas, lung and pleura showed scattered foci of fresh
fibrinoid change.
On re-examination of the liver biopsy specimen, the same
fibrinoid necrosis as observed on autopsy materials was seen in the
portal tracts.
DISCUSSION
The case reported here is characterized with unusual systemic fibrinoid
necroses in the walls of blood vessels and connective tissue in various
organs, especially in the liver. It is clear that massive fibrinoid
material around the bile ducts compressed the lumen and caused various
degrees of stenoses. It was considered that such stenosis of the bile
ducts resulted in the findings similar to those of PSC on the
cholangiogram[1,2]. Obstructive jaundice over time aggravated and
severely damaged the liver parenchyma. This was considered to reflect
the progressive deposition of fibrinoid material in the portal tracts.
Klemperer proposed the term, collagen diseases, to describe
systemic connective tissue disorders that are characterized
histologically by fibrinoid necrosis of the connective tissue[3,4].
Thereafter many studies clarified that fibrinoid material is composed
mainly of fibrins, while other minor components are immunoglobulins.
Although the pathogenesis of fibrinoid necrosis has not yet been fully
elucidated, it is assumed to result from the insudation of
immunoglobulins into blood vessel walls, leading to activation of the
coagulation cascade and deposition of fibrins[5]. Furthermore, fibrinoid
necrosis of blood vessels is also known to develop in non-autoimmune
diseases like malignant hypertension[6,7]. In our case laboratory
findings or symptoms were not suggestive of any autoimmune disease or
malignant hypertension. The liver pathology was also quite different
from that of reported cases with collagen diseases[8-10]. On a search of
the literature using key words such as fibrinoid necrosis, vasculitis,
we could not find any case similar to ours.
It is well known that the main cholangiographic features of
PSC are a beaded appearance, very short strictures, and diverticulum-like
outpourchings[11]. Cholangiographic differential diagnosis of PSC
involves cholangiocarcinoma, cirrhosis, acute cholangitis, and advanced
primary biliary cirrhosis in general[12]. In addition, it might be
necessary, in diagnosing PSC, to keep in mind that the lesions severely
involving the portal tracts like our case also cause severe damage,
besides stenosis of the biliary tracts.
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S- Editor Liu Y L- Editor Zhu LH
E- Editor Ma WH
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