Pathological changes of the pancreas in autopsied patients with SjS who had no pancreatic symptoms during life have been described. These changes include moderate levels of chronic pancreatitis, atrophy, replacement of pancreatic tissue by vascular connective tissue, and lymphocytic infiltration [5, 30, 31]. Autopsy of patients with SjS who had known pancreatic dysfunction showed similar histopathological findings to those reported previously in cases of asymptomatic patients [18].

18.3.5Imaging Studies of the Pancreas

Evaluation of a group of patients with SjS and elevated pancreatic enzymes revealed no specific alteration in the morphology of the pancreas as assessed by computed tomography [17]. Magnetic resonance cholangiopancreatography of asymptomatic patients with SjS showed chronic pancreatitis-like changes in 2 out of 12 patients. None of these patients had radiologic changes characteristic of autoimmune pancreatitis (AIP) [32].

18.4Autoimmune Pancreatitis

18.4.1Introduction

AIP is a fibroinflammatory disease of the pancreas. Although this disease was described initially by Sarles and colleagues in the early 1960s, wider recognition took another 50 years [33]. The revival of interest in this disease was triggered by a case report from Japan [13]. In addition to reporting their case, the authors identified a cohort of previously published reports that describe patients with enlarged pancreata, many of which were responsive to glucocorticoids. We now believe that these cases were examples of AIP. In a landmark paper, Hamano and coworkers identified serum IgG4 as a biomarker of AIP [34].

Following the observation by Hamano and colleagues in serum, investigators demonstrated that the diseased pancreas in AIP is infiltrated with large numbers of IgG4-positive plasma cells [35, 36]. It is likely but unproven that the intrapancreatic IgG4-bearing plasma cells are the source of elevated serum IgG4 concentration. Another potential contributor to serum IgG4 elevation is IgG4-producing plasma cells infiltrating other organs as part of systemic IgG4-RD. Immunohistochemical detection of IgG4-positive plasma cells in pancreatic tissue is now widely regarded as a robust marker of AIP [35–37].

As pathologists examined their archived cases of pancreatitis, it became apparent that not all cases of AIP were associated with elevated serum and tissue levels of IgG4. It is now accepted that there are two forms of the disease “autoimmune-medi- ated” pancreatic inflammation, currently termed type 1 and type 2 AIP. Of these two

disease subsets, type 1 AIP is now viewed as being part of the IgG4-RD spectrum [36, 38]. Types 1 and 2 AIP have overlapping clinical and radiological features, but distinct differences exist between the two groups with regard to histopathologic features and relapse rates. Type 2 AIP may in fact be a novel form of chronic pancreatitis that should be considered an entirely separate category of disease [38].

18.4.2Clinical Features

The type 1 variant of AIP typically affects elderly males in their 60s and 70s [36, 38]. The prototypical patient is an elderly man who presents with painless obstructive jaundice and weight loss. These patients show little overlap with other forms of chronic pancreatitis. Specifically, they do not report episodes of acute pancreatitis, although some complain of mild abdominal pain.

Patients with type 2 AIP are younger, with a mean age of 52 years [36]. Moreover, in contrast to type 1 AIP, which affects male patients almost exclusively, the male:female ratio in type 2 disease is approximately 1:1. At presentation, patients with type 2 AIP also show overlap with other forms of chronic pancreatitis. In one series, two thirds of patients had abdominal pain. In rare patients, more overt overlaps between acute and chronic pancreatitis are observed, with recurrent attacks of pancreatitis and pseudocyst formation.

Type 1 AIP is a systemic disease even though the pancreas may appear to be the sole manifestation of the disease at presentation. The presence of tumefactive lesions in other organ, either synchronously or metachronously, often clinch the diagnosis of AIP (see Table 18.2). For example, the finding of such extrapancreatic disease as tumefactive enlargement of the submandibular glands in an elderly male with obstructive jaundice strongly favors the diagnosis of AIP over that of pancreatic carcinoma. Type 2 AIP is less likely to have extrapancreatic manifestations, but there does appear to be a connection between type 2 AIP and inflammatory bowel disease.

Fig. 18.1 Fibroinflammatory infiltrate organized in a storiform pattern. This pattern of inflammation is seen both within the pancreas (autoimmune pancreatitis) and with IgG4-RD. Hematoxylin and Eosin stain

Fig. 18.2 Type 2 autoimmune pancreatitis. Note the periductal chronic inflammatory infiltrate (arrow head) and intraductal neutrophilic infiltrate (arrow). Hematoxylin and Eosin stain

presence of periductal inflammation. Type 1 AIP is characterized by a storiform fibroinflammatory infiltrate, obliterative phlebitis, and occasionally obliterative arteritis (however, necrotizing features are absent) [36] (Fig. 18.1). In contrast, type 2 AIP shows a ductal pattern of injury, the most characteristic features of which are intraductal neutrophilic infiltrates, with microabscesses [36] (Fig. 18.2). More severe forms of ductal injury are also seen – ulceration and total loss of epithelial cells. These findings can be detected on needle biopsy specimens, enabling nonoperative management in many cases. Tissue immunostains for IgG4 have proven to be robust ancillary markers for the diagnosis of AIP. The presence of greater than 50 IgG4-positive plasma cells per high power field and an IgG4:IgG ratio of >50% is virtually diagnostic of type 1 AIP. Biopsies from patients with type 2 AIP lack this feature.