|
Autoimmune pancreatitis: a systemic immune complex mediated disease.
Am J Surg Pathol. 2006 Dec;30(12):1537-45.
Autoimmune
pancreatitis (AIP) is a mass forming inflammatory pancreatobiliary-centric
disease. Recent reports of multiorgan inflammatory mass forming
lesions with increased numbers of IgG4 positive plasma cells suggest
that AIP may have a systemic component. In this study, we explore
the systemic nature of AIP, investigate the relevance of subtyping
AIP, perform a systematic study of tissue IgG4 immunoperoxidase, and
ultrastructurally evaluate the presence of immune complexes. Our
study group consisted of 36 patients with AIP, 21 of whom underwent
a Whipple procedure. On the basis of the pattern of inflammation,
pancreatic involvement was subtyped as ductocentric (AIP-D) or
lobulocentric (AIP-L). Extrapancreatic lesions included bile duct
(n=3), salivary glands (n=3), lung (n=2), gallbladder (n=11), and
kidney (n=4). Clinical and radiologic data was recorded.
Immunohistochemistry for IgG4 was performed on both pancreatic and
extrapancreatic tissues and the numbers of IgG4 positive plasma
cells were semiquantitatively scored. A control cohort composed of
pancreatic adenocarcinoma (n=19) and chronic pancreatitis-not
otherwise specified (NOS) (n=14) was also evaluated. Eleven
pancreatic specimens, including 2 cases of chronic pancreatitis-NOS
and 4 kidneys were evaluated ultrastructurally. The pancreas, bile
duct, gall bladder, salivary gland, kidney, and lung lesions were
characterized by dense lymphoplasmacytic infiltrates with reactive
fibroblasts and venulitis. IgG4 positive plasma cells were
identified in all pancreatic and extrapancreatic lesions. The AIP
cases showed significantly more pancreatic IgG4 positive plasma
cells than chronic pancreatitis-NOS or adenocarcinoma (P=0.001).
However, IgG4 positive cells were identified in 57.1% of chronic
pancreatitis-NOS and 47.4% of ductal adenocarcinoma. Fifteen of 21
resected cases were classified as AIP-D, and 6 as AIP-L, the latter
notably showing significantly more IgG4 positive plasma cells than
the former (P=0.02). Additionally, clinical and radiologic
differences emerged between the 2 groups. Ultrastructurally,
electron dense deposits of immune complexes were identified in the
basement membranes of 7 of the 9 AIP cases and in 3 of the 4 renal
biopsies evaluated. AIP represents the pancreatic manifestation of a
systemic autoimmune disease. Clinical and immunologic findings
justify the recognition of pancreatic lobulocentric and ductocentric
subtypes. Documentation of increased numbers of tissue IgG4 positive
plasma cells, although not an entirely specific marker for AIP, may
provide ancillary evidence for the diagnosis of a IgG4-related
systemic disease.
Comparison of radiological and histological findings in autoimmune
pancreatitis.Hepatogastroenterology.
2006 Nov-Dec;53(72):953-6.
BACKGROUND/AIMS: Autoimmune pancreatitis displays radiological
findings that are sometimes difficult to differentiate from
pancreatic carcinoma. To understand the essential radiological
features of autoimmune pancreatitis (AIP), we compared imaging and
histological findings in resected AIP specimens. METHODOLOGY:
Findings of ultrasonography, computed tomography, endoscopic
retrograde cholangiopancreatography and angiography were examined
retrospectively for 6 patients who underwent pancreatoduodenectomy
on suspicion of pancreatic carcinoma, and compared with histological
findings of the resected specimens. RESULTS: Ultrasonography showed
an enlarged hypoechoic pancreas with sausage-like appearance and no
lobulation in the contour of the pancreas. On computed tomography
imaging, delayed enhancement of the swollen pancreatic parenchyma
became evident. Dense lymphoplasmacytic infiltration with fibrosis
involving peripancreatic tissue was observed throughout almost the
entire pancreas. Periductal non-occlusive fibrosis with lympho
plasmacytic infiltration induced narrowing of the pancreatic duct.
Stenosis of the common bile duct is frequently associated with
autoimmune pancreatitis and is induced by diffuse thickening of the
duct wall by the same inflammatory process as that of the pancreas.
The fibroinflammatory process also involves blood vessels.
CONCLUSIONS: Characteristic radiological findings of autoimmune
pancreatitis are induced with systemic histological changes of
lymphoplasmacytic infiltration with fibrosis, and differ from
schirrous invasion of pancreatic carcinoma.
Involvement of pancreatic and bile ducts in autoimmune pancreatitis.
World J Gastroenterol. 2006 Jan 28;12(4):612-4.
AIM: To examine
the involvement of the pancreatic and bile ducts in patients with
autoimmune pancreatitis. METHODS: Clinical and
cholangiopancreatographic findings of 28 patients with autoimmune
pancreatitis were evaluated. For the purposes of this study, the
pancreatic duct system was divided into three portions: the ventral
pancreatic duct; the head portion of the dorsal pancreatic duct; and
the body and tail of the dorsal pancreatic duct. RESULTS: Both the
ventral and dorsal pancreatic ducts were involved in 24 patients,
while in 4 patients only the dorsal pancreatic duct was involved.
Marked stricture of the bile duct was detected in 20 patients and
their initial symptom was obstructive jaundice. Six patients showed
moderate stenosis to 30%-40% of the normal diameter, and the other
two patients showed no stenosis of the bile duct. Although marked
stricture of the bile duct was detected in 83% (20/24) of patients
who showed narrowing of both the ventral and dorsal pancreatic
ducts, it was not observed in the 4 patients who showed involvement
of the dorsal pancreatic duct alone (P=0.0034). CONCLUSION: Both the
ventral and dorsal pancreatic and bile ducts are involved in
patients with autoimmune pancreatitis.
Autoimmune pancreatitis: radiologic findings in 20 patients.Abdom
Imaging. 2006 Jan-Feb;31(1):94-102.
BACKGROUND:
Autoimmune pancreatitis is a new clinical entity that is
characterized by peculiar histopathologic and laboratory findings
and by a dramatic clinical response to corticosteroid therapy. We
evaluated the radiologic findings of autoimmune pancreatitis.
METHODS: Computed tomographic, magnetic resonance imaging,
endoscopic retrograde cholangiopancreatographic, and
ultrasonographic findings of 20 patients with autoimmune
pancreatitis in our hospital between November 2000 and December 2003
were retrospectively reviewed regarding changes and ancillary
findings in the pancreatic parenchyma, the main pancreatic duct,
peripancreatic vessels, and distal common bile duct. In addition,
follow-up images were reviewed for changes in any abnormality seen
on the initial examinations. RESULTS: Pancreatic parenchymal
enlargement was invariably seen that was diffuse (n = 19) or focal
(n = 1), with homogeneous contrast enhancement on computed
tomography (n = 20) and magnetic resonance imaging (n = 15).
Capsule-like rim enhancement was seen in six patients. There was
focal (n = 18) or diffuse (n = 2) narrowing of the main pancreatic
duct and it was usually multifocal (n = 17) in the former. Narrowing
of the peripancreatic veins was seen in 14 patients. There was
tapered (n = 15) or abrupt (n = 3) narrowing of the distal common
bile duct in 18 patients, with contrast enhancement of the narrowed
segment in eight. Invariably, changes in the pancreatic parenchyma,
main pancreatic duct, peripancreatic vessels, and common bile duct
were normalized on follow-up studies after steroid therapy.
CONCLUSION: In this series, common radiologic findings of autoimmune
pancreatitis were (a) diffuse pancreas enlargement, (b) multifocal
narrowing of the main pancreatic duct, (c) narrowing of
peripancreatic veins, and (d) tapered narrowing of the distal common
bile duct with frequent contrast enhancement. These findings were
usually reversible with steroid therapy.
Diagnostic
features and differential diagnosis of autoimmune pancreatitis.
Semin Diagn Pathol. 2005 Nov;22(4):309-17.
A clinically
and pathologically distinct form of chronic pancreatitis is now
widely recognized and has been designated variably as
lymphoplasmacytic sclerosing pancreatitis, duct-destructive
(duct-centric) pancreatitis or autoimmune pancreatitis. This entity
is currently defined by a constellation of clinical and pathologic
findings, including the lack of both conventional risk factors for
pancreatitis, such as alcohol use and gallstones, and their hallmark
pattern of injury, including calcifications and pseudocysts.
Histologically, it is characterized by lymphoplasmacytic
inflammation with abundant IgG4-positive plasma cells that exhibit
an affinity for ducts as well as venules ("peri-venulitis," with or
without frank vasculitis). Inflammation is often associated with
sclerosis and expansion of periductal tissue. In some cases,
fibroblastic activity is prominent and resembles "inflammatory
pseudotumor" or is even misdiagnosed as "inflammatory
myofibroblastic tumor." In what appears to be a distinct subset of
this entity, intraepithelial granulocytic infiltrates may be seen.
Well-developed examples are readily recognized; however, lesser ones
may be difficult to distinguish from other forms of pancreatitis
based on morphology alone. This type of pancreatitis is considered
an autoimmune process. In about 15% to 20% of patients, the clinical
stigmata of autoimmune conditions are present at the time of
diagnosis, and in many others, discovered subsequently. The usual "lymphoplasmacytic
sclerotic" type tends to be associated with Sjogren, whereas the
"granulocytic" subset, with inflammatory bowel disease. Most
patients present with a pancreatic head mass, often with an
accompanying stricture of the distal common bile duct, which thus
radiologically resembles "pancreas cancer." In fact, this entity
accounts for more than a third of the cases of pseudotumoral
pancreatitis (mass-forming inflammatory lesions that resemble
carcinoma). Elevated serum IgG4 levels are characteristic and may be
very helpful in the differential diagnosis from tumors and
tumor-like lesions of the pancreas which seldom result in levels
above 135 mg/dL. The mean age of the patients with this condition is
in the mid-50s; the subset with granulocytic intraepithelial lesions
seem to be younger (mid 40s). Despite the autoimmune association,
males are afflicted as commonly as (if not more than) females.
Following resection, emergence of new fibro-inflammatory lesions in
the remaining pancreaticobiliary tree has been noted in some cases;
however, the process typically responds to steroids. It is important
to recognize the distinctive clinicopathologic features of this
entity, so that it can be diagnosed accurately and managed
appropriately.
Morphological changes after steroid therapy in autoimmune
pancreatitis.
Scand J Gastroenterol. 2004 Nov;39(11):1154-8.
BACKGROUND:
Although many patients with autoimmune pancreatitis undergo steroid
therapy, detailed evaluation of morphological changes in the
pancreas and bile duct following therapy has not been performed in
this disease. In this study serological and morphological changes
occurring during steroid treatment of autoimmune pancreatitis are
comparatively examined. METHODS: Ten patients with autoimmune
pancreatitis were treated with corticosteroids. Morphological
findings were: pancreatic enlargement (n = 9), irregular narrowing
of the main pancreatic duct (n = 10), and biliary stenosis (n = 9).
An initial dose of prednisolone was 40-30 mg/day, and this was
tapered by 5 mg every 1-2 weeks. All patients underwent ultrasound
and serological testing 1-2 weeks after commencing medication,
followed by weekly serological testing and by CT and endoscopic
retrograde cholangiopancreatography after 1-2 months. Radiological
and serological changes were compared. RESULTS: All 10 patients were
responsive to steroid therapy. Pancreatic size normalized within 1
month; however, irregularity of the pancreatic duct remained in 6
patients. Rigidity or lateral deformity of the bile duct remained in
3 patients and biliary stenosis persisted in 5. Four patients in
whom elevated serum IgG4 failed to normalize also showed incomplete
morphological improvement. Three patients with complete improvement
of the pancreatic duct stopped medication, but recurrence of
pancreatitis did not occur. CONCLUSIONS: Although steroid therapy
was morphologically and serologically effective in patients with
autoimmune pancreatitis, cholangiopancreatographic abnormalities
remained in many patients. Morphological improvement on
cholangiopancreatography and normalization of serum IgG4 after
steroid therapy appeared to be good indicators for discontinuing
medication in patients with autoimmune pancreatitis.
A new
clinicopathological entity of IgG4-related autoimmune disease.J
Gastroenterol. 2003;38(10):982-4.
BACKGROUND:
Autoimmune pancreatitis (AIP) is occasionally associated with other
autoimmune diseases. METHODS: To investigate the pathophysiology of
AIP, we immunohistochemically examined the pancreas and other organs
in eight patients with AIP, and in controls, using anti-CD4-T and
CD8-T cell subsets, as well as IgG4 antibodies. RESULTS: In AIP
patients, severe or moderate infiltration of IgG4-positive plasma
cells associated with CD4- or CD8-positive T lymphocytes was
detected in the peripancreatic tissue (6/6), bile duct (8/8),
gallbladder (8/8), portal area of the liver (3/3), gastric mucosa
(5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes
(6/6), and bone marrow (2/2), as well as in the pancreas (8/8).
There were few IgG4-positive plasma cells at the same sites in
controls. CONCLUSIONS: These results suggest that AIP is not simply
pancreatitis but that it is a pancreatic lesion involved in
IgG4-related systemic disease with extensive organ involvement. We
propose a new clinicopathological entity, of a systemic IgG4-related
autoimmune disease in which AIP and its associated diseases might be
involved.Autoimmune pancreatitis (AIP) is occasionally associated
with other autoimmune diseases.
Involvement of the
biliary system in autoimmune pancreatitis: a follow-up study.Clin
Gastroenterol Hepatol. 2003 Nov;1(6):453-64
BACKGROUND &
AIMS: The aim of this study was to define the bile duct changes
associated with autoimmune pancreatitis. METHODS: Eight patients
with autoimmune pancreatitis were followed for a mean of 4 years.
The clinical features of these patients, including extrapancreatic
bile duct changes, were examined by using biochemical parameters and
several imaging modalities. Pathologic features of the pancreas and
liver were examined by using the biopsy specimens of 7 patients.
RESULTS: Diffuse or focal narrowing of the main pancreatic duct was
observed in all patients. Histologic examination of the pancreas
showed lymphoplasmacyte infiltration with severe fibrosis and acinar
cell depletion. In 6 patients extrapancreatic bile duct changes such
as stricture of the bile duct at hilus or intrahepatic area were
observed. In 2 patients abnormalities in the bile duct and pancreas
were detected simultaneously at diagnosis, and changes in the bile
duct were observed later in 4 patients. Lymphoplasmacyte
infiltration and fibrosis were observed in the portal area of all 7
liver biopsy samples. Five of the patients with bile duct changes
received steroid therapy, and the pathological changes improved.
CONCLUSIONS: Extrapancreatic bile duct changes are frequently
associated with autoimmune pancreatitis. Similar pathogenic
mechanism might produce the biliary tract and pancreatic
abnormalities in autoimmune pancreatitis resulting in a similar
histopathology in the liver and pancreas and response to steroid
therapy.
|
