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World J Gastroenterol 2014 December 14; 20(46): 17674-17679
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
Submit a Manuscript: http://www.wjgnet.com/esps/
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DOI: 10.3748/wjg.v20.i46.17674
© 2014 Baishideng Publishing Group Inc. All rights reserved.
CASE REPORT
Focal autoimmune pancreatitis and chronic sclerosing
sialadenitis mimicking pancreatic cancer and neck
metastasis
Li Sun, Qiang Zhou, David R Brigstock, Su Yan, Ming Xiu, Rong-Li Piao, Yan-Hang Gao, Run-Ping Gao
Li Sun, Qiang Zhou, Su Yan, Ming Xiu, Rong-Li Piao, YanHang Gao, Run-Ping Gao, Department of Hepatic-BiliaryPancreatic Medicine, First Hospital, Jilin University, Changchun
130021, Jilin Province, China
David R Brigstock, Research Institute at Nationwide Children’s
Hospital, Columbus, OH 43205, United States
David R Brigstock, Division of Pediatric Surgery, Department
of Surgery, Ohio State University, Columbus, OH 43205, United
States
Author contributions: Sun L, Zhou Q, Yan S, Xiu M, Piao RL
and Gao YH performed the experiments and analyzed data; Gao
RP designed the study and wrote the manuscript; Brigstock DR
co-ordinated the study and edited the manuscript.
Supported by National Natural Scientific Foundation, No.
81070370, and No. 81270544 to Gao RP; and National Institutes
of Health, No. 5R01AA016003 to Brigstock DR
Correspondence to: Run-Ping Gao, Professor, Department
of Hepatic-Biliary-Pancreatic Medicine, First Hospital, Jilin University, 71 Xinmin Avenue, Changchun 130021, Jilin Province,
China. gao_runping@yahoo.com
Telephone: +86-431-81715110 Fax: +86-431-85612468
Received: May 1, 2014
Revised: June 8, 2014
Accepted: July 11, 2014
Published online: December 14, 2014
Abstract
Type 1 autoimmune pancreatitis (AIP) or chronic sclerosing sialadenitis (Küttner’s tumour) is an uncommon
disorder that has recently been confirmed as an IgG4related disease. Here, we describe a rare case of a
53-year-old male patient who primarily presented with
pancreatic body mass, left neck mass and several lumps
in his lower lip mimicking pancreatic cancer (PC) and
neck metastasis. The patient underwent pancreatic
body mass and labial gland lumps resection as well as
an ultrasound-guided biopsy of the left neck mass. He
was diagnosed with IgG4-related focal type of AIP (f-AIP)
and Küttner’s tumour by immunohistochemistry. The
patient responded well to corticosteroid therapy and
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remains healthy with no signs of recurrence at one year
follow-up. The differentiation of f-AIP from PC is very
important to avoid unnecessary pancreatic resection.
© 2014 Baishideng Publishing Group Inc. All rights reserved.
Key words: IgG4-related disease; IgG4-related focal
type of AIP; Küttner’s tumour; Autoimmune pancreatitis; Pancreatic cancer
Core tip: We report a rare case of 53-year-old male
patient who suffered from IgG4-related focal type of
autoimmune pancreatitis (f-AIP) accompanied with Küttner’s tumour originally suspected of being pancreatic
cancer with neck metastasis. The patient responded
well to corticosteroid therapy but he had undergone an
unnecessary pancreatic body mass resection one year
ago prior to admission. Therefore, we suggest that AIP
should always be considered in case of a focal pancreatic mass.
Sun L, Zhou Q, Brigstock DR, Yan S, Xiu M, Piao RL, Gao
YH, Gao RP. Focal autoimmune pancreatitis and chronic
sclerosing sialadenitis mimicking pancreatic cancer and neck
metastasis. World J Gastroenterol 2014; 20(46): 17674-17679
Available from: URL: http://www.wjgnet.com/1007-9327/full/
v20/i46/17674.htm DOI: http://dx.doi.org/10.3748/wjg.v20.
i46.17674
INTRODUCTION
Autoimmune pancreatitis (AIP) is an uncommon form of
chronic pancreatitis associated with an autoimmune inflammatory process[1]. Two subtypes of AIP have been so
far recognized: type 1 AIP is the pancreatic manifestation
of IgG4-related disease (IgG4-RD), while type 2 AIP
is related to a granulocytic epithelial lesion[2,3]. Although
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December 14, 2014|Volume 20|Issue 46|
Sun L et al . IgG4-related focal autoimmune pancreatitis
A
B
C
Figure 1 Rare computed tomography images of type I autoimmune pancreatitis. A same image with pancreatic cancer (PC) in the body of the pancreas (white
arrow) one year ago prior to admission (A), a similar image of pancreatic head carcinoma (white arrow) accompanied by common bile duct dilation (black arrow) at
admission (B), and slightly reduced in the pancreatic head volume (white arrow) with a normal common bile duct (black arrow) after steroid therapy (C).
diffuse swelling of the pancreatic parenchyma and diffuse irregular narrowing of the pancreatic duct system
are morphologically characteristics of both subtypes of
AIP, a focal type of AIP (f-AIP) has been recently recognized[4]. The f-AIP exhibits a localized mass lesion in the
pancreas, which closely mimics pancreatic cancer (PC)[4,5].
Since AIP responds extremely well to steroid therapy, the
differentiation of AIP from PC is highly important to
avoid unnecessary laparotomy or pancreatic resection.
Chronic sclerosing sialadenitis (Küttner’s tumour) is
a benign tumour-like lesion most commonly affecting
the submandibular gland first recognized by Küttner in
1896[6]. Histologically it is characterized by acinar atrophy,
periductal sclerosis, and perilobular lymphocytic infiltrate.
Recently, Küttner’s tumour has been recognized within
the spectrum of IgG4-RD because some samples of
sclerosing sialadenitis from Japan or America have abundant IgG4-positive plasma cells[7]. Although unusual cases
that affect the parotid glands or labial glands have also
been described[8], Küttner’s tumour arising in the unilateral submandibular gland and synchronously affecting the
focal salivary gland in lower lip has not been reported.
Here, we report a rare case of a patient with IgG4related f-AIP accompanied with Küttner’s tumour manifesting itself as a mass in the neck and several lumps in
the lower lip, which was originally misdiagnosed of being
PC with neck metastasis.
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CASE REPORT
A 53-year-old male from Northeast China was admitted
for abdominal distension and diarrhea lasting for four
years. He presented a painless, hard left neck mass with
slight dysfunction of salivary secretion and a 20-pound
weight loss over 6 mo. One year prior to admission,
positron emission tomography/computed tomography
(PET/CT) (data not shown) or CT imaging identified a
possible pancreatic body carcinoma resulting in surgical
resection of the pancreatic body and tail with en-bloc
splenectomy at that time. However, the diagnosis of pancreatic carcinoma was ruled out after a routine histological examination was performed (Figure 1A). The patient
denied any history of alcohol, tobacco, or illicit drug use.
On examination, several firm 0.3 cm non-tender lumps
were seen in the mucosa of his lower lip. He also had a
painless, hard, fixed mass in the left submandibular area
(suspected cervical metastasis). Abdominal examination
revealed mild epigastric tenderness to deep palpation
without rebound.
The laboratory test data on admission revealed a
markedly elevated erythrocyte sedimentation rate (74
mm/h), and a mildly elevated serum amylase (158 U/L)
and lipase (109 U/L). Serum immunological testing displayed high levels of IgG4 (32.7 g/L) and IgG (38.9 g/L),
and positive reaction with anti-nuclei antibody.
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December 14, 2014|Volume 20|Issue 46|
Sun L et al . IgG4-related focal autoimmune pancreatitis
A
B
C
D
Figure 2 Histological findings of the excisional biopsy specimen of the lower lip lumps. Hematoxylin and eosin (HE) stain showing normal labial gland (A, ×
400); acinar atrophy and lymphoplasmacyte infiltration and fibrosis from the patient (B, × 400); immunohistochemical staining for IgG4 (red color) (C, × 400) or IgG
(yellow color) (D, × 400) in plasma cells from the patient.
An ultrasound scan of the neck showed left swollen
submandibular gland (4.2 cm length × 2.8 cm width ×
2.1 cm height), suggesting the possibility of chronic sialadenitis. An enhanced CT scan of the abdomen revealed
a relatively low density of the pancreatic head as well as
extra- and intra-hepatic bile duct dilatation (Figure 1B),
suggesting the possibility of pancreatic head cancer.
On the 10th day after admission, we suspected neck
metastasis of pancreatic head cancer or multiple tumors
of the salivary glands or IgG4-related systemic disease.
The patient underwent an excisional biopsy examination
of the lower lip lumps to obtain definitive histological
diagnosis. In distinction from healthy individuals, hematoxylin and eosin (HE) staining of the excisional biopsy
specimen revealed acinar atrophy, abundant lymphocytoplasma cell infiltration, and marked fibrosis (Figure
2A, B). Immunohistochemical staining showed abundant
IgG4-postive plasma cells in the excisional labial gland
specimen of the patient, with a ratio of IgG4/IgGpositive plasma cells of more than 50% (Figure 2C, D).
Fine needle aspiration biopsy (FNA) of the left submandibular gland showed changes consistent with labial gland
spencimen (data not shown). The patient was diagnosed
with Küttner’s tumour which affected left submandibular
gland and labial salivary gland.
To determine weather the patient suffered from
IgG4-related autoimmune pancreatitis, pancreatic specimens that had been obtained from the patient by excision of the body mass of the pancreas one year prior to
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this admission were stained with HE which revealed the
presence of phlebitis (Figure 3A), storiform-type fibrosis and dense lymphoplasmacyte infiltration (Figure 3A,
B). Immunohistochemical staining showed numerous
IgG4-positive plasmacytic infiltrations around the intact
pancreatic ducts, with a ratio of IgG4/IgG-positive plasmacytes of more than 40% thus meeting the diagnostic
criteria for IgG4-related f-AIP (Figure 3C, D).
On the 17th day after admission, the patient received
30 mg/d of prednisone for 4 d without any side effects,
and was then discharged with the same steroid dose for
up to 4 wk. At his 4-wk follow-up, the patient exhibited
no signs of either abdominal distension or diarrhea. His
previously swollen submandibular gland on the left side
was markedly reduced but still palpable, while the epigastric region was not painful upon deep palpation. A
CT scan of the abdomen showed slight reduction of the
pancreatic head volume or in the extra- and intra-hepatic
bile duct dilatations (Figure 1C). The previously elevated
serum levels of amylase and lipase had returned to normal value ranges, but serum IgG4 level was still high (15.6
g/L). The patient then received a long-term maintenance
dose of 10 mg/d of prednisone after steroid tapering. At
12-mo follow-up, his illness had not recurred.
DISCUSSION
IgG4-RD is a recently recognized multi-organ fibroinflammatory condition with a propensity to manifest
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December 14, 2014|Volume 20|Issue 46|
Sun L et al . IgG4-related focal autoimmune pancreatitis
A
B
C
D
Figure 3 Histological findings of the resected specimen from pancreatic body mass. Hematoxylin and eosin (HE) stain showing phlebitis (A, × 200); numerous
lymphoplasmacyte infiltration and storiform fibrosis (B, × 200); immunohistochemical staining showing IgG4-positive plasma cells (C, × 400) and IgG-postive plasma
cells (D, × 400) in the resected pancreatic sections of the patient.
itself as a mass-forming lesion characterized by the presence of abundant IgG4+ plasma cells, elevation of serum
IgG4 levels, and a dramatic steroid responsiveness[9]. New
histological diagnostic criteria for IgG4-RD require the
presence of at least two of three characteristic histological features, namely, dense lymphoplasmacytic infiltration,
fibrosis arranged at least focally in a storiform pattern,
and obliterative phlebitis[10]. Thus, the patient in this study
fully met the diagnostic criteria for IgG4-related f-AIP
and Küttner’s tumour.
Although diagnosis of AIP has greatly improved
because of growing awareness of the condition and proposed diagnostic criteria[3,10], there still remain no good
practical strategies to distinguish AIP from PC. Clinicians
must differentiate between the two disorders to prevent
unnecessary surgery or delayed initiation of corticosteroid therapy. It has been reported that about 2.5% of
pancreatic resections were performed in AIP patients
following a mistaken diagnosis of PC[11] and that 35.3%
of f-AIP patients were surgically treated because PC was
suspected[12]. The patient in this study underwent surgical resection of the pancreatic body mass one year prior
to admission, which we subsequently histologically confirmed as IgG4-related f-AIP.
Over the last decade, clinicians have paid great attention to the differentiation of AIP from PC. Recently Sun
et al[13] reported that five radiological imaging features
helpful for diagnosing f-AIP were (1) sausage-shaped
enlargement; (2) delayed homogeneous enhancement; (3)
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hypoattenuating capsule-like rim; (4) irregular narrowing
of the main pancreatic duct (MPD) and/or stricture of
the common bile duct; and (5) MPD upstream dilatation
≤ 5 mm. Since focal mass and pancreatic duct dilatation are the most common findings for PC as well[14],
differentiating such cases of f-AIP from PC is rather difficult using CT or magnetic resonance imaging alone. A
recent study showed that serum IgG4 > 280 mg/dL or
other organ involvement (exapancreatic biliary stricture,
salivary gland swelling and retroperitoneal fibrosis) were
highly specific findings for f-AIP[15]. More recently, 18Ffluorodeoxyglucose (FDG)-PET/CT could be used to
monitor the drug efficacy of IgG4-RD because abnormal
FDG uptake in all affected lesions had completely disappeared after therapy[16]. Although endoscopic ultrasoundguided FNA (EUS-FNA) is useful to either diagnose or
rule out PC, definitive diagnosis of AIP is difficult by
EUS-FNA because of the small sample size obtained[11].
Recently, EUS-guided core biopsy techniques are recommended[11]. IgG4 immunostaining of biopsy specimens
obtained from the major duodenal papilla was also used
for diagnosis of AIP[17]. Therefore, comprehensive data
including clinical, imaging, serological, histological differences and other organ involvement should be analyzed to
differentiate f-AIP from PC.
The patient in this study responded well to corticosteroid therapy. However, after 4-wk steroid therapy the
serum IgG4 level was still high (15.6 g/L). Since IgG4
antibodies are directly pathogenic in IgG4-RD, rituximab
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December 14, 2014|Volume 20|Issue 46|
Sun L et al . IgG4-related focal autoimmune pancreatitis
therapy is chosen to realize rapid decline of serum IgG4
levels and prompt clinical improvement in IgG4-RD by
depleting the pool B lymphocytes that replenish shortlived IgG4-secreting plasma cells[18]. Additionally, steroid
sparing regimens such as Azathioprine and mycophenolate mofetil may be used in patients with incomplete
response to steroid.
In summary, we report a rare case of IgG4-related
f-AIP and Küttner’s tumour which primarily mimics
pancreatic cancer and neck metastasis. Since the differentiation of f-AIP from PC is very difficult and their
treatment and prognosis are quite different, we suggest
that AIP should always be considered in case of a focal
pancreatic mass.
REFERENCES
1
2
3
4
COMMENTS
COMMENTS
5
Case characteristics
A 53-year-old male patient primarily presented with pancreatic body mass, left
neck mass and several lumps in his lower lip mimicking pancreatic cancer (PC)
and neck metastasis.
Clinical diagnosis
The patient was diagnosed with IgG4-related focal type of autoimmune pancreatitis (f-AIP) and Küttner’s tumour.
Differential diagnosis
The differential diagnosis included PC with neck metastasis and other malignant tumors in the neck region.
6
7
Laboratory diagnosis
The patient was diagnosed with IgG4-related f-AIP and Küttner’s tumour on the
basis of numerous IgG4-positive plasma cells in excisional pancreatic mass
sample and labial gland specimen, and also had a high serum IgG4 level.
8
Imaging diagnosis
Computed tomography (CT) showed a same image with PC in the body of the
pancreas one year ago prior to admission and a similar image of pancreatic
head carcinoma at admission. An ultrasound scan of the neck showed left swollen submandibular gland.
9
Pathological diagnosis
The patient underwent pancreatic body mass and labial gland lumps resection.
He was diagnosed with IgG4-related f-AIP and Küttner’s tumour by immunohistochemistry.
10
Treatment
The patient received 30 mg/d of prednisone for 4-wk, and a long-term maintenance dose of 10 mg/d of prednisone.
Related reports
IgG4-related AIP or Küttner’s tumour has been reported previously, however,
IgG4-related f-AIP accompanied with Küttner’s tumour maneifesting itself as a
mass in the neck and several lumps in the lower lip has not yet been described.
Term explanation
Chronic sclerosing sialadenitis, also known as Küttner’s tumour is a benign
tumor lesion most commonly affecting the submandibular gland first recognized
by Küttner in 1896. Recently, Küttner’s tumour has been recognized within the
spectrum of IgG4-related disease because some samples of sclerosing sialadenitis from Japan or America have abundant IgG4-positive plasma cells.
Experiences and lessons
11
12
This case reports IgG4-related f-AIP accompanied with Küttner’s tumour which
primarily mimics PC and neck metastasis. Since the differention of f-AIP from
PC is quite difficult, the authors suggest that AIP should always be considered
in case of a focal pancreatic mass.
13
This is an important case from the awareness point of view, and also of the
prognosis being far more positive than that of pancreatic cancer with metastasis. The manuscript is interesting and well written.
14
Peer review
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17678
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P- Reviewer: Gonzalez-Granado LI, Khan S, Murdaca G
S- Editor: Nan J L- Editor: A E- Editor: Ma S
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