When Pathology Marries Clinics

Generoso Uomo
Department of Internal Medicine, Cardarelli Hospital. Naples, Italy
Autoimmune pancreatitis has been extensively
described in reports from the Far East, Europe and the
USA. The diagnosis was based on the presence of four
main criteria related to histological findings,
radiological features, other organ involvement, and
clinical and instrumental response to steroid therapy [1,
2, 3, 4, 5, 6]. As defined in these terms, the diagnostic
approach and general management of autoimmune
pancreatitis seems to be quite “linear” but the subject
presents a lot a controversial aspects, namely,
concerning histopathology (microscopic and macro-
scopic) as well as clinical findings.
Large series of patients observed in Japan have been
identified as affected by autoimmune pancreatitis based
on distinct clinical features, without the need for
histology to confirm this diagnosis. On the contrary,
detailed descriptions of at least two histopathological
patterns (i.e. lymphoplasmacytic sclerosing pancreatitis
without granulocytic epithelial lesions and idiopathic
duct-centric pancreatitis with granulocytic epithelial
lesions) have been reported in Europe and the USA to
define the presence of autoimmune pancreatitis,
independently from the clinical phenotypes. In
particular, the presence of granulocytic epithelial
lesions associated with idiopathic duct-centric
pancreatitis is considered a hallmark of autoimmune
pancreatitis in Europe while lymphoplasmacytic
sclerosing pancreatitis represents the basis for the
diagnosis in the USA. Accordingly, the identification
of two types of autoimmune pancreatitis has been
proposed: type 1 autoimmune pancreatitis
(histopathological pattern of lymphoplasmacytic
sclerosing pancreatitis) and type 2 autoimmune
pancreatitis (pattern of idiopathic duct-centric
pancreatitis). Differences in serology and clinical
presentation between these two forms are also
described. Type 1 autoimmune pancreatitis presents
high levels of serum IgG4 levels and nonspecific
autoantibodies, prevalence of male gender, more
advanced age, frequent involvement of other organs
(salivary glands, biliary tract, kidney, lung,
retroperitoneum) and possible relapse of the disease
after steroid treatment. On the contrary, type 2
autoimmune pancreatitis does not have definite
serologic autoimmune markers, the affected patients
are younger without any gender difference, only the
colon may be involved (ulcerative colitis) and relapse
after steroids is infrequent. In Japan, only type 1
autoimmune pancreatitis is considered an autoimmune
disorder with the identification of a distinct
clinicopathological entity, called “IgG4-related
sclerosing disease” [7]. In addition, this entity was
recently considered a partial expression of a
lymphoproliferative disease called “IgG4 positive
multiorgan lymphoproliferative syndrome”, a more
complex, multiorgan disorder with the possible
inclusion of Mikulitcz’s disease, Küttner tumors,
inflammatory pseudotumors (of the lung, liver, and
breast), mediastinal fibrosis and autoimmune
hypophysitis [8]. The subject is even more complicated
by the fact that autoimmune pancreatitis may be
macroscopically focal or diffuse [9]. Focal autoimmune
pancreatitis is characterized by segmental involvement
of the parenchyma with the possibility of a low-density
mass being present at imaging. The Italian proposal for
the diagnosis of autoimmune pancreatitis, which is
different from that suggested in Japan and the USA, is
based on the instrumental distinction between the focal
and the diffuse forms of the disease [10]. In the case of
focal autoimmune pancreatitis, particularly in the
presence of a low-density pancreatic mass, the clinical
challenge is to exclude pancreatic cancer and correctly
diagnose the autoimmune pancreatitis whereas diffuse
autoimmune pancreatitis may be confused with acute
Key words Autoimmune Diseases; Pancreatic Neoplasms;
Pancreatitis, Chronic; Practice Guidelines as Topic
Correspondence Generoso Uomo
Department of Internal Medicine; Cardarelli Hospital; via
Cardarelli 9; 80131 Napoli; Italy

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JOP. J Pancreas (Online) 2011 Jul 8; 12(4):431-432.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 12 No. 4 - July 2011. [ISSN 1590-8577]
pancreatitis or with cholangiocarcinoma when jaundice
secondary to a common bile duct stricture is present.
Recently, a group of international experts proposed a
consensus document [11] with the aim of overcoming
controversy on the histopathology and clinics of
autoimmune pancreatitis. In summary, the main
statements of this article are: a) autoimmune
pancreatitis has unique histopathological features
which allow it to be differentiated from other forms of
chronic pancreatitis; b) there are definite histologic
criteria for lymphoplasmacytic sclerosing pancreatitis
and idiopathic duct-centric pancreatitis; c) the two
histopathologically distinct types of autoimmune
pancreatitis are associated with distinct clinical
profiles; d) the clinical phenotypes associated with the
histopathological patterns of lymphoplasmacytic
sclerosing pancreatitis and idiopathic duct-centric
pancreatitis should be referred to as type 1 and type 2
autoimmune pancreatitis, respectively. Starting from
this consensus document, the same group of experts
has more recently published a comprehensive article
[12] which represents the guidelines of the
International Association of Pancreatology on
autoimmune pancreatitis. The distinction of
autoimmune pancreatitis into types was confirmed but
the diagnosis of type 1 and type 2 autoimmune
pancreatitis was categorized as definite or probable in
relation to the diagnostic reliability of each of the five
cardinal features of autoimmune pancreatitis, namely,
imaging of the pancreatic parenchyma and duct,
serology, other organ involvement, pancreatic
histology, and an optional criterion of response to
steroid therapy. In addition, a new category was
identified (autoimmune pancreatitis not otherwise
specified) for some cases in which the distinction
between the two subtypes of autoimmune pancreatitis
was not possible.
These articles are a praiseworthy and successful
attempt of promoting worldwide recognition and
optimal management of autoimmune pancreatitis in
clinical practice.
Conflict of interest The author has no potential
conflicts of interest
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