two cases of autoimmune pancreatitis with coexisting...

Case ReportSt. Marianna Med. J.Vol. 37, pp. 261�267, 2009

Two Cases of Autoimmune Pancreatitis with Coexisting Features of

Tumor-Forming Pancreatitis.

Satoshi Kitajima1, Minoru Kobayashi1, Shunitirou Ozawa1, Ryujiro Negushi1,

Mami Hirakawa1, Hirokazu Obara1, Nobuyuki Obinata1, Masahito Nomoto1,

Tadateru Maehata1, Takashi Tuda1, Takefumi Kouro1, Takeshi Sawada1,

Yoshiyuki Watanabe1, Toshiya Ishii2, Akira Nikai2, Akira Sato2,

and Fumio Itoh1

�Received for Publication: June 11, 2009�

Abstract

Case 1: A 61-year-old male was hospitalized for evaluation of jaundice. The antinuclear antibody

�ANA� titer was 160, and rheumatoid factor �RF� was positive. Contrast abdominal CT showed di#useenlargement of the pancreas and a mass in the pancreatic head. ERCP revealed localized narrowing in the

main pancreatic duct in the pancreatic body. The patient was diagnosed as having autoimmune pancreatitis

�AIP�. Treatment with predonisolone �PSL� improved the pancreatic enlargement and reduced the size of themass in the pancreatic head. Case 2: A 74-year-old male was hospitalized with suspected cancer of the

pancreatic head. Serum IgG was 2,212 mg�dl, IgG4 was 915 mg�dl, and the anti-DNA antibody titer was 4.Abdominal US and abdominal contrast CT showed di#use enlargement of the pancreas and a mass in the

pancreatic head. As the jaundice decreased with endoscopic naso-biliary drainage, the pancreatic enlarge-

ment improved, and the mass in the pancreatic head decreased in size. Based on the clinical course, the

patient was diagnosed with AIP. Both of these patients appear to have had AIP with coexisting features of

tumor-forming pancreatitis �TFP�. Thus, AIP should be considered as an etiology of nonalcoholic TFP. Oneof the two patients initially diagnosed based on the 2002 diagnostic criteria for AIP had a confirmatory

diagnosis based on the 2006 revised clinical diagnostic criteria for AIP. Patients should be re-evaluated based

on the later criteria.

Key Words

Autoimmune Pancreatitis, Tumor-Forming Pancreatitis

Introduction

Autoimmune pancreatitis �AIP� was first de-scribed in 1961 by Sarles et al.1� as a chronic infla-

mmatory sclerosis of the pancreas involving an

autoimmune mechanism. In Japan, since 1992,

when Toki et al.2� reported a case of chronic pan-

creatitis with di#use irregular narrowing of the main

pancreatic duct, the number of cases has increased.

On the other hand, tumor-forming pancreatitis

�TFP� is often referred to clinically in the di#erentialdiagnosis of pancreatic cancer, but TFP is not a

well-defined clinical entity.3� In this report, we de-

scribe two patients with AIP and coexisting features

of TFP.

1 Department of Internal Medicine, Division of Gastroenterology and Hepatology, St. Marianna University School ofMedicine.2 Department of Gastroenterology, St Marianna University School of Medicine Yokohama Seibu Hospital.

261

85

Case Reports

Case 1: This 61-year-old male developed general-

ized malaise and dark urine in late August of 2002

and was hospitalized by his physician for evaluation

of hepatic dysfunction. The history was negative for

alcohol consumption. Physical examination re-

vealed jaundice and scleral icterus. Abdominal ex-

amination revealed a palpable, nontender mass be-

neath the right subcostal margin. Laboratory data

on admission included a blood sedimentation rate

of 61 mm�h �moderately elevated�, a direct bilirubinof 5.1 mg�dl, an antinuclear antibody �ANA� titer of160, and a positive rheumatoid factor �RF�. Con-trast abdominal CT during the parenchymal phase

showed di#use enlargement of the pancreas and a

mass in the pancreatic head, but a corresponding

low-density area suspicious of pancreatic cancer

was not present �Fig 1a, b�. MRCP showed narrow-ing of the lower common bile duct and localized

narrowing of the main pancreatic duct �Fig. 2a�.PTBD was performed for obstructive jaundice.

PTC showed smooth extrinsic narrowing of the

lower common bile duct margin �Fig. 3a�. OnERCP, localized narrowing of the main pancreatic

duct in the pancreatic body, but no post-stenotic

dilation, was observed. In addition, there was no

narrowing or obstruction of the main pancreatic

duct in the pancreatic head �Fig. 3b�. On cholan-gioscopy, there was no irregularity or redness of the

common bile duct mucosa; thus, the narrowing was

due to extrinsic compression. Based on these fin-

dings, the patient was diagnosed as having AIP, and

treatment with predonisolone �PSL� 30 mg per day

Figure 1. Contrast abdominal CT image of case 1 during the parenchymal phase.

a: CT showed di#use enlargement of the pancreas.

b: A mass was seen in the pancreatic head, but a corresponding low-density area suspicious of pancreatic

cancer was not present. The arrow indicates a mass in the pancreas head.

Figure 2. MRCP image of case 1.

a: MRCP showed narrowing of the lower common bile duct and localized narrowing of the main

pancreatic duct.

b: Narrowing of the lower common bile duct improved after treatment with PSL.

Kitajima S Kobayashi M et al262

86

was started. The pancreatic enlargement and nar-

rowing of the lower common bile duct improved

�Fig. 2b�.

Case 2: This 74-year-old male began to experience

left-sided abdominal pain in March 2003. In May

2003, he noticed clay-colored stools and jaundice.

Since abdominal CT showed enlargement of the

pancreatic head, he was admitted to hospital with

suspected pancreatic cancer. His alcohol consump-

tion consisted of one bottle beer per day. Physical

examination revealed jaundice and scleral icterus.

Abdominal examination revealed an elastic, hard

mass on the left side; the patient complained of

abdominal pain in the area of the mass, with associ-

ated tenderness on palpation. Laboratory data on

admission showed a blood sedimentation rate of 30

mm�h �mildly elevated�, direct bilirubin of 10.8mg�dl, serum IgG of 2,212 mg�dl, IgG4 of 915mg�dl, and an anti-DNA antibody titer of 4. Con-trast abdominal CT during the parenchymal phase

showed di#use enlargement of the pancreas and a

low-density mass in the pancreatic head �Fig. 4a, b�.On abdominal US, sausage-shaped enlargement of

the entire pancreas, a 5-cm mass in the pancreatic

head, and mild dilation of the main pancreatic duct

in the pancreatic body were present �Fig. 5a, b�.Contrast abdominal MRI showed no di#erence in

signal intensity between the pancreatic parenchyma

and the mass in the pancreatic head. MRCP showed

no significant dilation in the main pancreatic duct

of the pancreatic body and tail, but intrahepatic bile

duct dilation and lower common bile duct narrow-

ing were present �Fig. 6�. On ERCP, as on MRCP,intrahepatic bile duct dilation and smooth narrow-

ing of the lower common bile duct margin were

observed. Contrast visualization of the main pan-

creatic duct was di$cult. Endoscopic naso-biliary

drainage was performed, and the jaundice im-

proved. After catheter removal, there was no exac-

erbation of jaundice, and contrast abdominal CT

showed improvement in the pancreatic enlargement

and a reduction in size of the mass in the pancreatic

head �Fig. 4c, d�. The patient’s symptoms improvedduring follow-up.

Discussion

Interest in AIP has increased, with a growing

number of case reports. Etemad and Whitcomb4�

have proposed a new classification for chronic pan-

creatitis �TIGAR-O�, which includes AIP as an eti-ology. In 2002, the Japan Pancreas Society pub-

lished diagnostic criteria for AIP. In the present

report, the diagnosis of AIP in our patients was

based on these 2002 diagnostic criteria for AIP. 5� In

patient 1, with pancreatic enlargement, positive

ANA, and positive RF, the criteria regarding nar-

rowing of the main pancreatic duct were not met.

Patient 2 had a history of alcohol consumption, but

pancreatic calcification and irregular pancreatic

Figure 3. PTC and ERCP image of case 1.

a: PTC showed smooth extrinsic narrowing of the lower common bile duct margin. The arrow indicates

narrowing of the lower common bile duct margin.

b: Localized narrowing of the main pancreatic duct in the pancreatic body, but no post-stenotic dilation,

was observed. In addition, there was no narrowing or obstruction of the main pancreatic duct in the

pancreatic head. The arrow indicates localized narrowing of the main pancreatic duct in the pancreatic

body.

AIP Coexist Tumor-Forming Pancreatitis 263

87

Figure 4. Contrast abdominal CT image of case 2 during the parenchymal phase.

a, b: CT showed di#use enlargement of the pancreas and a low-density mass in the pancreatic head. The

arrow indicates a mass in the pancreas head.

c, d: CT showed improvement in the pancreatic enlargement and a reduction in size of the mass in the

pancreatic head after endoscopic naso-biliary drainage.

Figure 5. Abdominal US image of case 2.

a: US showed sausage-shaped enlargement of the entire pancreas.

b: US showed a 5-cm mass in the pancreatic head and mild dilation of the main pancreatic duct in the

pancreatic body were present. The arrow indicates a mass in the pancreas head.


88

margins, as defined in the diagnostic criteria for

chronic pancreatitis, were not present. Di#use en-

largement of the pancreas was observed. Elevated

IgG and IgG4 levels suggested AIP, but ERCP did

not visualize the main pancreatic duct, thus not

meeting the diagnostic criteria. However, in patient

1, based on the revised clinical diagnostic criteria

for AIP in 2006,6�7� except for narrowing of�1�3 ofthe main pancreatic duct, the diagnostic criteria

were fitted. In addition, elevated IgG4 is reported to

be useful in the di#erential diagnosis between AIP

and other disorders, including pancreatic cancer,8�9�

and in the 2006 clinical diagnostic criteria for AIP,

elevated IgG4 is listed. Therefore, in patient 2, even

though the main pancreatic duct was not visualized

with contrast, the findings were consistent with AIP.

Among the case reports that we reviewed, AIP was

often diagnosed, as in our patients, based on clini-

cal findings, even though all diagnostic criteria were

not fitted. Re-evaluation based on the revised

guidelines is necessary.10�11�

TFP is a clinical entity that is often di$cult to

distinguish from cancer and may represent the so-

called tumor-forming stage of dynamically chang-

ing chronic pancreatitis.3� The etiology of TFP is

broadly classified as alcoholic and nonalcoholic,

and in the latter, an autoimmune mechanism is

thought to play a role.12� TFP often involves the

pancreatic head, but as compared to pancreatic

cancer, the incidence of jaundice and obstruction �narrowing of the main pancreatic duct is lower.

Even if the main pancreatic duct is narrowed, dila-

tion of the pancreatic duct in the pancreatic tail is

usually not present. Furthermore, smooth narrow-

ing of the common bile duct is often observed.13� The

di#erential diagnosis between TFP and pancreatic

cancer, especially with tumor fibrosis, can be

di$cult based on CT or MRI contrast e#ects in the

parenchyma. In these cases, the “duct penetrating

sign” may be useful in the di#erential diagnosis.14�

AIP is usually associated with di#use pancreatic

enlargement, but localized enlargement can also

occur. This can be a factor in TFP, and, in particu-

lar, when the pancreatic head is enlarged, the di#e-

rential diagnosis with pancreatic cancer may be

di$cult. However, when pancreatic head enlarge-

ment is part of more di#use pancreatic enlargement,

the presence of a capsule-like rim around the pan-

creas is helpful in diagnosis. Histologically, this is a

fibrous capsule, so on dynamic CT or MRI, there is

gradual enhancement.15� Our each patient also had

mass in the pancreatic head, making it di$cult to

distinguish from pancreatic cancer, but the di#use

pancreatic enlargement and absence of main pan-

creatic duct dilation helped in the di#erential diag-

nosis.

However, in AIP, narrowing of the common

bile duct within the pancreas can cause obstructive

jaundice, thus making it di$cult to di#erentiate

from pancreatic head cancer or bile duct cancer.

The narrowing often occurs in the lower common

bile duct and is relatively smooth; it is probably due

to compression by the enlarged pancreas, but coex-

isting biliary lesions in AIP have also been

reported.16� It is necessary to care for diagnosis be-

cause CT and�or intraductal ultrasound show

thickening of the bile duct wall, and the findings in

some cases may resemble primary sclerosing

cholangitis.17�18� Both of our patients had smooth

narrowing of the lower bile ducts, but no other

findings were evident.

Conclusions

1. We reported two patients with AIP and coexist-

ing features of TFP.

2. Much remains unknown about the etiology of

TFP, but in nonalcoholic TFP, underlying AIP

should be kept in mind.

3. Suspected cases of AIP should be re-evaluated

based on the revised clinical diagnostic criteria for

AIP.

Figure 6. MRCP image of case 2.

MRCP showed no significant dilation in the main

pancreatic duct of the pancreatic body and tail, but

intrahepatic bile duct dilation and lower common bile

duct narrowing were present.


89

Reference

1� Sarles H, Sarles JC, Muratore R and Guien C.Chronic inflammatory sclerosis of the pan-

creas-an autonomous pancreatic disease? Am J

Dig Dis 1961; 6: 688�698.2� Toki F, Kozu T and Oi I. An unusual type ofchronic pancreatitis showing di#use irregular

narrowing of the entire main pancreatic duct

on ERCP-A report of four cases. Endoscopy

1992; 24: 640.

3� Kuroda A and Yahata K. Cancer-mimickingpancreatitis. Kan Tan Sui 1988; 17: 1191�1198.�In Japanese�

4� Etemad B and Whitcomb C. D. Chronic Pan-creatitis: Diagnosis, Classification, and New

Genetic Developments. Gastroenterology

2001; 120: 682�707.5� Members of the Criteria Committee for Auto-immune Pancreatitis of the Japan pancreas So-

ciety. Diagnostic Criteria for Autoimmune

Pancreatitis by the Japan Pancreas Society

�2002�. J. JPN. PANC. SOC 2002; 17: 585�587.6� Members of the Autoimmune Pancreatitis Di-agnostic Criteria Committee, the Research

Committee of Intractable Diseases of the Pan-

creas supported by the Japanese Ministry of

Health, Labor and Welfare, and Members of

the Autoimmune Pancreatitis Diagnostic Crite-

ria Committee, the Japan Pancreas Society.

Clinical diagnostic criteria of Autoimmune

Panceratitis 2006. J. JPN. PANC. SOC 2006;

21: 395�397.7� Kamisawa T, Okazaki K and Kawa S. Diag-nostic criteria for autoimmune pancreatitis in

Japan . World J Gastroenterol 2008; 28: 4992�4994.

8� Hamano H, Kawa S, Horiuchi A, Unno H,Furuya N, Akamatsu T, Nikaido T,

Nakayama K, Usuda N and Kiyosawa K.

High serum IgG4concentrations in patients

with sclerosing pancreatitis. N Engl J Med

2001; 344: 732�738.9� Kamisawa T, Okamoto A and Funata N.Clinicopathological features of autoimmune

pancreatitis in relation to elevation of serum

IgG4. Pancreas 2005; 31: 28�31.

10� Horiuchi A, Kawa S, Hamano H, Ota H andKiyosawa K. ERCP features in 27 patients with

autoimmune panceratitis. Gastrointestinal En-

doscopy 2002; 55: 494�499.11� Ozaki T, Takai S, Satoi S, Yanagimoto Y,

Kwon A. H and Kamiyama Y. A case of auto-

immune pancreatitis with localized irregular

narrowing of the main pancreatic duct and

acute interstitial nephritis successfully treated

with corticosteroid therapy. J. JPN. PANC.

SOC 2004; 19: 425�431.12� Takase M and Suda K. Histopathological

study on mechanism and background of tu-

mor-forming pancreatitis. Pathology Interna-

tional 2001; 51: 349�354.13� Kobayashi T, Fujita N, Noda Y, Kimura A

and Yago T. Diagnosis of Inflammatory Pseu-

dotumor of the Pancreas by ERCP and EUS.

Tan to Sui 1999; 20: 285�292. �In Japanese�14� Ichikawa T, Sou H, Araki T, Arbab A. S,Yoshikawa T, Ishigame K, Haradome H and

Hachiya J. Duct-penetrating Sing at MRCP:

Usefulness for Di#erentating Inflammatory

Pancreatic Carcinomas. Radiology 2001; 221:

107�116.15� Irie H, Harada H, Baba S, Kuroiwa T,Yoshimitsu K, Tajima T, Jimi M, Sumii T and

Masuda K. Autoimmune pancreatitis : CT and

MR characteristics. AJR 1998; 170: 1323�1327.16� Ichimura T, Kondou S, Ambo Y, Hirano S,Ohmi M, Okushiba S, Morikawa T, Shimizu

M and Katoh H. Primary Sclerosing Cholangi-

tis Associated with Autoimmune Pancreatitis.

Hepat-Gastroenterology 2002; 49: 1221�1224.17� Nakazawa T, Sano H, Ohara H and Itoh M.

Di#erence between biliary lesions associated

with chronic pancreatitis exhibiting di#use ir-

regular narrowing of the main pancreatic duct

and primary sclerosing cholangitis. J. JPN.

PANC. SOC 2002; 17: 645�654.18� Mendes F. D, Jorgensen R, Keach J, Katz-

mann J. A, Smyrk T, Donlinger J, Chari S, and

Lindor K. D. Elevated Serum IgG4 Concentra-

tion in Patients with Primary Sclerosing

Cholangitis. Am J Gastroenterol 2006; 101:

2070�2075.


90

�� 2��

��

��

��

��

1 ��

��

1 ��

1 ��

1

��

��

��

��1 �

�

��

��

��1 �

�

��

��

��

�!�1 �

�

�"�

��

��1

��#

�$�

��%

& 1 !

'

"%

#��

$�1 %

��

��

&�(

')�1 �

��

"%

(�(�

1

)��

��*

*+�

+!�1 ,

��

-�

��

.2

,

/��

0-��

2 1�

2��

3-��

2

4�

5��

6)�

7�1

� �8� 1: 619:;<. =�>?@A. BCBD 160E/ FGHIJKL<. MNOP CT >

?�QD:R�S�TN:R�UVWXYZ. ERCP [\DN]�^>_`<abcUdXYZ. efgh<�iSjk/ lmnopqrstuv/ �R�:wxS�TNR�:y�UzXYZ. 8� 2: 749:;<. �TN{|}>?@A. IgG 2212 mg�dl/ IgG4 915 mg�dl/B DNA BD 4E. MN US, MNOP CT >?�TN:R�S�QD:R�UdXYZ. ~=SS�>�R�:wx/ �TNR�:y�UzXY/ ��efgh<�iS��vZ.�0\efgh<�i>R��<�i:��U��vZSjkXY� 28�s��vZ. ��<:R��<�i:��>efgh<�i��T>��U��SjkXYZ. �Z��\|}8�[��Z 28�:� 18�\efgh<�i��¡¢ 2002£¤Xefgh<�i¥¦��¡¢ 2006§:w¨>��©��Sª�/ 8�:«¬��Sjk�.

1 ®HF�r¯°±�² ³±²�´µ¶�·¸³±�2 ®HF�r¯°±�²¹º»¼N�A ´µ¶³±


91

two cases of autoimmune pancreatitis with coexisting...

Documents