Autoimmune pancreatitis is rare disease with a much lower rate of incidence than its principal differential diagnosis, pancreatic cancer. The overall incidence and prevalence are still unclear owing to lack of prospective natural history studies. Study series from Japan have reported the prevalence of autoimmune pancreatitis in a range between 5 and 6% of all patients with chronic pancreatitis of which 6–8% (0.82 per 100,000) had pancreatic resections performed for presumed pancreatic cancer [4, 5]. Moreover, in the last two decades, there has been an increase in the number of reports of autoimmune pancreatitis in the medical literature; however, the overall number of patients is still relatively small. Though this clinical entity was well described initially in Japan, a growing awareness of the condition has led to reports around the world. Hamano et al. [6] reported that serum IgG4 levels are specifically elevated in Japanese patients with AIP; however, in further reported case series by Hirano et al. [7] and Pezzilli and Corinaldesi [8], an increase of IgG4 levels in AIP cohorts has been also confirmed in Western and Eastern countries. Although the pathogenesis of the disease is unknown, current evidence strongly suggests that an autoimmune process has been implicated [9, 10]. Unlike most autoimmune conditions, AIP has a male predominance, with a male : female ratio of 2 : 1. The peak age of onset is the sixth and seventh decades [5, 9, 11].

The histopathological hallmark findings in patients with AIP include dense infiltration of T lymphocytes, IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis in the pancreas; this form is termed lymphoplasmacytic sclerosing pancreatitis (LPSP) [12–14]. Of late, recent studies have provided evidence that there is another subtype of AIP with different histological findings named as idiopathic duct-centric pancreatitis (IDCP) that is more prevalent in Europe and the United States [15, 16]. Recent studies showed consensus that LPSP and IDCP are regarded as two distinct subtypes of AIP, and it has been proposed that LPSP be called “type 1 AIP” and IDCP “type 2 AIP” [17, 18].

In 2011, an international panel of experts met during the 14th Congress of the International Association of Pancreatology held in Fukuoka, Japan, and an international consensus diagnostic criterion for AIP was proposed [19]. According to these, AIP is classified into type 1 and 2. Five cardinal features of AIP are used: imaging of pancreatic parenchyma and ducts; serology; other organ involvement; pancreatic histology; and an optional criterion of response to steroid therapy. Each feature is categorized as a level 1 or 2 finding, depending on the diagnostic reliability (as shown in Table 1).

AIP should always be included in the differential diagnosis particularly in elderly presenting with obstructive jaundice and a pancreatic mass. Prior to initiation of therapy, it is of paramount importance to differentiate AIP from pancreatic cancer. Various strategies help differentiate the clinical, immunological, and radiological presentations in between AIP and pancreatic cancer. Obstructive jaundice induced by bile duct stenosis secondary to pancreatic cancer typically progresses steadily, whereas the jaundice of AIP in IgG4-related sclerosing disease sometimes fluctuates or, in rare cases, improves spontaneously [13, 20]. Elevated serum levels of IgG4 (>135 mg/dL) are seen in more than 90% of patients with AIP [6]. This is the most sensitive and specific diagnostic test for type I AIP, with 95% sensitivity, 97% specificity, and 97% accuracy for discrimination from pancreatic cancer [6]. Ghazale et al [21] in their study series of pancreatic cancer patients 13/135 (10%) noted that elevation of serum IgG4 levels alone cannot rule out pancreatic cancer, as only 1% of the above patients had elevated IgG4 levels >280 mg/dL, compared with 53% of AIP patients. Presence of other organ involvements such as bilateral salivary gland swelling, retroperitoneal fibrosis, and hilar or intrahepatic sclerosing cholangitis is highly suggestive of AIP rather than pancreatic cancer.

Radiological studies aid in differentiation based on the characteristic features on computed tomography (CT) and magnetic resonance imaging (MRI) that include diffuse or focal pancreatic enlargement, a peripancreatic capsule-like rim, enhancement at the late phase of contrast-enhanced images, and abnormal signal intensity on MRI. Diffuse enlargement of the pancreas and effacement of the lobular contour of the pancreas, the so-called “sausage-like” appearance, are a typical finding in AIP and are rarely seen in pancreatic cancer. On delayed phase of dynamic CT and MRI, enhancement of an enlarged pancreas is characteristic of AIP. As fibroinflammatory changes involve the peripancreatic adipose tissue, a capsule-like rim surrounding the pancreas is specifically detected in some AIP patients [22, 23]. The role of transabdominal ultrasonography in the diagnosis of autoimmune pancreatitis is not well established. Ultrasonographic images of the pancreas, obtained transabdominally, are rarely diagnostic of autoimmune pancreatitis. Furthermore, findings on ultrasonography may be similar for autoimmune pancreatitis and for other forms of acute and chronic pancreatitis.

The hallmark finding on endoscopic retrograde cholangiopancreatography (ERCP) in patients with autoimmune pancreatitis is diffuse or segmental attenuation of the main pancreatic duct (MPD), in contrast to the segmental stenoses often encountered with pancreatic adenocarcinoma. The other common findings are narrowing of the intrapancreatic portion of the common bile duct, irregular narrowing of extrahepatic bile ducts, and, less frequently, enlarged intrahepatic bile ducts [24]. It is of paramount importance to reliably distinguish AIP from PSC as making a reliable diagnosis is critical due to the often dramatic response of AIP related biliary strictures to steroid therapy in contrast to equivocal response seen in primary sclerosing cholangitis (PSC) and cholangiocarcinoma. The presence of a long, monomorphic stenosis of the intrapancreatic bile duct is suggestive of AIP, while band-like strictures, beading, or prune-tree appearance is most often found in PSC. Magnetic resonance cholangiopancreatography (MRCP) has become popular as a noninvasive method and it is becoming preferable to diagnostic ERCP. However, the narrowest MPD seen on ERCP cannot be visualized by MRCP due to the inferior resolution of MRCP compared with ERCP, so distinguishing between narrowing of the MPD in AIP and stenosis of the MPD in pancreatic cancer is not possible [25].

Endoscopic ultrasonography (EUS) emerged as a particularly important pancreatic imaging tool due to its ability to provide high-resolution imaging along with short working distances for transluminal pancreatic interventions. Though nonspecific, most common finding on EUS is diffuse or focal pancreatic enlargement inhomogeneous echo pattern, stranding and calcification [26]. EUS guided fine-needle aspiration or core biopsy of the pancreas may aid in the cytologic or histologic diagnosis; however, this approach to tissue acquisition was generally proven inadequate in providing a definitive diagnosis of AIP owing to a small sample size and lack of preserved tissue architecture and has not been evaluated in larger trials [26, 27].