Case Report


Figure 3: Magnetic Resonance Cholangiopancreatography Performed One Year after Steroids and Azathioprine


demonstrating periductal lymphoplasmacytic infiltrate with obliterative phlebitis and storiform fibrosis and/or the presence of 10 or more IgG4-postive cells per high power field on immunostaining of the lymphoplasmacytic infiltrate; (B) imaging showing a diffusely enlarged pancreas and a diffusely irregular, narrow pancreatic duct with elevated serum IgG4 ≥140mg/dl; or (C) unexplained pancreatic disease with negative work-up especially for malignancy, together with elevated IgG4 levels ≥140mg/dl or other organ involvement confirmed by the presence of abundant IgG4 positive cells and resolution or marked improvement in pancreatic or extrapancreatic manifestations with steroid therapy.10,31


There is complete resolution of the distal common bile stricture (horizontal arrow) and marked improvement of the irregular beaded narrowing of the main pancreatic duct (vertical arrows).


of life and without a gender preference.10,11 In contrast to type I AIP, type


II disease is rarely associated with extrapancreatic involvement. The disease is more likely to affect the pancreas focally and is associated with inflammatory bowel disease in up to 30% of cases.20–22


The diagnosis of AIP can be difficult. Serum IgG4 levels are usually elevated but can be misleading as not all patients with AIP have elevated IgG4 levels. When a serum IgG4 cut-off of 140mg/dl is used, two large US series found the sensitivity to be 44–75% and the specificity 93%.23,24 Cross-sectional imaging with CT scan or MRI typically shows diffuse enlargement of the pancreas with loss of lobularity, the so-called ‘sausage-pancreas’, delayed and peripheral enhancement of the rim resulting in a ‘halo’ appearance, or ‘saran wrap’ sign.10–12,25,26 density mass often mimics pancreatic adenocarcinoma.11,27


A focal, low- ERCP findings


in AIP include diffuse narrowing of the main pancreatic duct with beading12


but is not routinely performed for diagnosis in developed countries. MRCP shows similar pancreatic findings but can also be very helpful in indentifying extrapancreatic involvement such as retroperitoneal fibrosis and renal infiltrates.


EUS features in the acute presentation can include a diffusely enlarged, hypoechoic lobular gland with smooth borders, a diminutive pancreatic duct, and diffuse concentric thickening of the bile duct that extends into the extrapancreatic duct.12


EUS-guided fine-needle aspiration is


generally considered inadequate to confirm the diagnosis and a pancreatic core biopsy is preferred to appreciate the full spectrum of features of AIP on histology.12,27,28


Diagnostic criteria have been proposed


by the Japanese Pancreas Society (I and II), the South Korean classification system, and the Mayo Clinic (HISORt criteria).29–31


Recently,


the Asian consensus criteria were developed based on the Japanese and Korean criteria.32


The HISORt criteria includes five major


components: histology; imaging; serology; other organ involvement; and response to steroid treatment.31


diagnosed if the patient falls into one of three groups: (A) histology 70 Based on the HISORt criteria, AIP can be


The Asian Consensus criteria involve three categories: imaging; serology; and pathology. The main difference between the HISORt and the Asian Consensus criteria is that the Asian criteria require ductal imaging by ERCP whereas the HISORt criteria allow ERCP or MRCP. The Asian criteria also require surgical pathology, whereas the HISORt criteria allow for a core or endoscopic biliary biopsy. These diagnostic criteria are geared towards type 1 AIP and do not address type II AIP where patients are typically seronegative and found to have exuberant ductocentric granulocytic epithelioid lesions on histology.12,21


Although our patient did not have elevated serum IgG4 levels, he had typical imaging findings of extrapancreatic involvement and abundant IgG4 positive plasma cells on submandibular gland biopsy. His disease responded dramatically to steroid therapy, thereby meeting HISORt criteria for the diagnosis of AIP. There are limited data on the use of PET scan in diagnosing AIP and demonstrating extrapancreatic involvement, which can be helpful in differentiating AIP from pancreatic adenocarcinoma.1,33 has also been used to assess response to steroid therapy25


PET but further


studies are needed to determine the role of PET in the diagnosis and management of AIP. IgG4-associated cholangitis is characterized by elevations of serum IgG4 and infiltration of IgG4-positive plasma cells in bile ducts, often mimicking cholangiocarcinoma.34 thought to be a local manifestation of ISD.


Similar to AIP, this is


AIP typically responds dramatically to steroids but a relapse rate of up to 40% is seen when steroids are tapered.35,36


Relapses may be treated


with repeat courses of steroids, but long-term immunosuppressive therapy with an immunomodulator such as azathioprine is frequently needed. The use of mycophenolate mofetil, cytoxan, or ritixumab have also been reported.10–12,37 long-term survival.20


Limited studies suggest that AIP does not affect


Our case highlights the diverse clinical spectrum of AIP and ISD and the clinical challenge in differentiating this condition from either pancreatic or cholangiocarcinoma. AIP is a rare entity and clinicians should always maintain a high suspicion for malignancy. A comprehensive approach to the diagnosis through the use of various diagnostic criteria and, preferably, histologic confirmation is likely to decrease the probability of misdiagnosing pancreatic or biliary malignancy as ISD. In selected patients with features highly characteristic of ISD, an empiric steroid trial may be considered without histologic or serologic evidence for ISD. An optimal steroid or immunosuppressive regimen and duration of treatment have not been established in controlled studies. Long-term studies are needed to both define the natural history of the disease and the efficacy of corticosteroid or immunosuppressive medications. n


US GASTROENTEROLOGY & HEPATOLOGY REVIEW


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