'I GO FOR' (IG4) Autoimmune pancreatitis (AIP) and extrapancreatic imaging features.

'I GO FOR' (IG4) Autoimmune pancreatitis (AIP) and extrapancreatic imaging features. Poster No.: C-2649 Congress: ECR 2013 Type: Educational Exhibit Authors: R. P. Patel, T. M. Chandler, S. Barrett, J. Coyle, C. Zwirewich, 1 4 1 1 2 2 3 3 1 4 A. Harris ; Vancouver, BC/CA, Dublin/IE, Cork/IE, CA Keywords: Abdomen, Pancreas, CT, MR, Ultrasound, Diagnostic procedure, Inflammation Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 38

Learning objectives An exhibit of the multimodality US/CT/MRI/fluoroscopic imaging characteristics of autoimmune pancreatitis to aid in the differentiation of AIP from malignant pancreatic processes. To illustrate other extra-pancreatic imaging features. The role of imaging in follow up after treatment with steroids. Background Autoimmune pancreatitis (AIP) is the pancreatic manifestation of IgG4 related sclerosing disease which was recently recognized as distinct disease entity. Known as a benign disease process, it can clinically mimic pancreatic cancer. Early diagnosis and management is important as it can slowly progress to end stage pancreatic disease. Numerous extrapancreatic organs may be involved either synchronously or metachronously. Most cases of AIP are associated with elevated IgG4 levels; extensive IgG4 positive plasma cells; and infiltration of lymphocytes into various organs which lead to fibrosis. It is important to recognize multiorgan involvement of IgG4 related sclerosing disease and be familiar with its clinical and imaging features because it demonstrates a favourable response to corticosteroid treatment. Imaging findings OR Procedure details Multi-modality imaging and enhancement characteristics of pancreatic features. Multimodality imaging of extrapancreatic pathological processes; biliary tree dilatation Page 2 of 38

lacrimal adenitis siladenitis renal inflammatory pseudotumour prostatitis aortitis retroperitoneal fibrosis Follow up imaging after steroid therapy. Pancreatic features Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis accounting for 1.5-11% of all cases Pathogenesis is though to involve antibodies, hypergammaglobulinemia and evidence of lymphoplasmocytic inflammation and fibrosis Highly responsive to steroids The role of imaging is to make a prompt diagnosis so that steroids can be implemented in a timely fashion Three recognized patterns; Diffuse, focal and multifocal Men>women (15:2) 14-85yrs, mean age 60yrs Signs and symptoms: Can be fluctuating obstructive jaundice, vague abdominal pain, weight loss, steatorrhea and diabetes Focal; painless jaundice, weight loss Diffuse; epigastric pain radiating to back AIP can clinically mimic pancreatic adenocarcinoma Diagnostic evaluation Clinical features alone not helpful A short-term trial of high-dose steroid therapy with repeat imaging can be utilized to look for a reduction in size of the pancreatic parenchymal and normalization of the pancreatic duct. Page 3 of 38

Serology; Serum IgG4 is statistically higher in patients with AIP than in other populations (e.g. pancreatic cancer), other autoantibodies are raised (rheumatoid factor and antinucleur) Imaging; Mayo clinic: utilizes CT features only, Japan relies on ERCP and CT features Histology; Core biopsies can be used to confirm the presence of abundant IgG4 positive plasma cells and lymphocyte infiltration Diffuse parenchymal enlargement Fig 1-8 40-60% AIP cases Pancreatic borders become featureless with effacement of the lobular contour 'sausage pancreas' Typical imaging features: CT; A halo of soft tissue attenuation present in 12-40% Enhancement characteristics Hypoattenuating in early phase Hyperattenuating in the late phase MRI; T1 diffusely hypointense T2 mildly hyperintense Early phase heterogeneously diminished enhancement Late phase delayed enhancement USS Diffusely enlarged and hypoechoic Focal, mass like or segmental enlargement of the pancreas Fig 9-17 30-40% AIP cases Most commonly pancreatic head involvement Can mimic pancreatic adenocarcinoma radiologically Enhancement characteristics Focal mass like enlargement Iso or hypoattenuating to the spared non enlarged segment Parenchymal atrophy Page 4 of 38

5-20% pts Likely represents a late burn out phase of disease Also seen after steroid therapy AIP vs. Pancreatic adenocarcinoma: Distinguishing features Capsule-like rim around the pancreas Seen only in AIP Contrast enhancement BOTH adenocarcinoma and focal AIP are hypoattenuating on arterial phase ONLY adenocarcinoma is hypoattenuating on PV phase, whereas AIP on delayed imaging demonstrates retention of contrast with near- normal enhancement (and appears nearly isoattenuating to the normal pancreatic parenchyma). Duct dilatation The pancreatic duct within the lesion is not visible in either AIP or adenocarcinoma - NOT a useful feature Upstream main pancreatic duct dilatation (e.g.> 5mm) seen more often in adenocarcinoma. Extrapancreatic features Prevalence of extrapancreatic findings is 92% Familiarity with these findings can help to make the diagnosis of AIP when the pancreatic findings are ambiguous. Distribution: Retroperitoneum (retroperitoneal fibrosis, AAA) 20% Renal (renal pseudotumours) 14% Biliary (wall thickening and multifocal strictures) 78% Prostate(enlargement) 10% Salivary/ lacrimal gland (enlargement), lymph nodes - 48% Lung (inflammatory nodules, chronic bronchitis, NSIP, LIP) 13% Retroperitoneal fibrosis Fig 18-20 Present in 10%-20% of patients Similar imaging characteristics as those of retroperitoneal fibrosis Manifestations Soft tissue mass surrounding the abdominal aorta (and branches) and IVC Soft tissue mass surrounding the ureters (may result in hydronephrosis) Page 5 of 38

Paravertebral mass Pelvic retroperitoneal mass May be difficult to distinguish from periaortitis as some cases of AIP are associated with AAA Renal pseudotumors Fig 21,22 renal lesions associated with AIP may be difficult to differentiate from pyelonephritis or infarcts - look for ancillary pancreatic and extra-pancreatic findings to help make the diagnosis Pathophysiology: Due to dense lymphocytic infiltration of the renal interstitium Lesions vary from tubulointerstitial nephritis (TIN) to tumor like masses depending on the distribution Most lesions progress to cortical scars at follow up evaluation Appearance: Bilateral and multiple Poorly enhancing, mild enhancement on delayed phase images 4 patterns: Round or wedge shaped renal cortical nodules Peripheral cortical lesions Mass like lesions Renal pelvic involvement Biliary abnormalities Fig 23, 24, 25 The most common form of extrapancreatic involvement which can occur in the absence of pancreatic findings. May progress and lead to biliary cirrhosis AIP associated biliary involvement may mimic primary sclerosing cholangitis (PSC), therefore look for ancillary pancreatic and extrapancreatic findings to aid diagnosis CT; Focal or diffuse thickening and enhancement of the bile duct wall Rarely soft tissue mass that can resemble cholangiocarcinoma GB involvement appears as diffuse thickening of GB wall ERCP Multifocal intra +/- extrahepatic bile duct strictures or thickening Prostate Fig 26 May be difficult to distinguish from prostate cancer and prostatitis. A trial of steroids or a biopsy may be needed to confirm abundant IgG4 positive plasma cell and lymphocytic infiltration Page 6 of 38

Imaging: Prostate enlargement Hypodense Surrounding fat stranding Salivary gland/lymph nodes Fig 27, 28, 29 Distribution Submandibular 76% Lacrimal 75% Parotid 13% Sublingual 5% Affected lymph nodes may be as large as 2cm (exhibit infiltration by IgG4 positive plasma cells) Imaging: Salivary gland involvement in AIP may clinically mimic Sjogren's syndrome. MRI may provide useful distinguishing features; In Sjorgren's the lesions tend to have a 'salt and pepper' appearance, a feature which is not seen in AIP - salivary involvement MRI; Bilateral homogenous swelling of the glands without a discernible mass USS; Multiple hypoechoic nodules Images for this section: Page 7 of 38

Fig. 1: CECT axial CT in 62 yo female with AIP. Pancreas diffusely enlarged with a 'sausage' type appearance. Page 8 of 38

Fig. 2: Grayscale USS showing diffusely enlarged hypoechoic gland with 'sausage' like appearance (arrow) in 62 yo female with AIP. Page 9 of 38

Fig. 3: Follow up imaging in the same patient after steroid treatment. The diffuse enlargement has subsided and the pancreas has a more normal morphology, but is atrophic indicative of the late burnt out phase of disease. Page 10 of 38

Fig. 4: Initial contrast-enhanced CT in a 65 year old male with AIP. The pancreas is diffusely enlarged and there is a hypodense capsule like rim (arrows). Page 11 of 38

Fig. 5: Follow up imaging after a course of steroid treatment. The pancreas has reacquired its normal morphology and appearance, but is atrophic indicative of the late burnt out phase of disease. The hypodense capsule is no longer seen. Page 12 of 38

Fig. 6: Axial CECT in a 55 yo man presenting with epigastric pain and jaundice. 'Sausage' shaped diffusely enlarged pancreas, loss of fatty lobulation and surrounding 'halo' of low attenuation. Page 13 of 38

Fig. 7: Coronal CECT in the same 55yo patient which demonstrates CBD wall enhancement, thickening, dilatation (arrow) and proximal intrahepatic biliary duct dilatation. Page 14 of 38

Fig. 8: ERCP of 55 yo man which shows distal CBD stricture (arrow). Page 15 of 38

Fig. 9: CECT 55 yo male with focal hypodense mass in the pancreatic head (arrow), biliary stent in situ. Adenocarcinoma and focal AIP are often indistinguishable as illustrated. Radiologists need to know about this form of AIP in order to prevent invasive treatment. This patient underwent a Whipple procedure and AIP was diagnosed at pathology. Page 16 of 38

Fig. 10: Axial T2 MR 61 yo male with a a focal T2 hypointense mass in the pancreatic head. Page 17 of 38

Fig. 11: Axial CECT 61 yo old male shows mildly hypoattenuating focal pancreatic head mass (arrow). Page 18 of 38

Fig. 12: Focal AIP in 61 yo axial T2 MR, note the mild associated upstream pancreatic duct dilatation. Page 19 of 38

Fig. 13: Focal AIP in 61 yo axial CECT, note the mild upstream pancreatic duct dilatation. The patient went on to have a Whipple's procedure, subsequently proven to be AIP on histology. Page 20 of 38

Fig. 14: MRCP coronal T2 from the same 61 yo patient demonstrated the focal mass in the pancreatic head (arrow). Mild upstream main pancreatic duct dilatation and parenchymal atrophy. Page 21 of 38

Fig. 15: ERCP in the 61 yo patient, demonstrates marked narrowing of the intrapancreatic portion of the distal CBD (arrow). Page 22 of 38

Fig. 16: Axial CECT showing focal hypoattenuating enlarged pancreatic body (arrow) relative to the rest of the pancreas in a 51 yo with Serology and biopsy proven AIP. Page 23 of 38

Fig. 17: Axial CECT showing normal homogenous pancreatic enhancement (arrow) and resolution of appearances in 51 yo with AIP following steroid treatment. Page 24 of 38

Fig. 18: Axial CECT in a 65 yo with AIP. A rind of soft tissue is seen surrounding the abdominal aorta (arrow). Page 25 of 38

Fig. 19: Axial CECT post steroid treatment in 65 yo with AIP. The previously seen periaortic soft tissue mass has resolved (arrow). Page 26 of 38

Fig. 20: Coronal CECT in a 55 yo man with AIP. There is peri-aortic soft tissue (arrow) and an inflammatory abdominal aortic aneurysm (AAA). Note the CBD wall enhancement, thickening and CBD dilatation. Page 27 of 38

Fig. 21: Axial CECT 65 yo male with AIP and bilateral renal masses (arrows). These appear as wedge shaped hypodense areas which could be confused with pyelonephritis or other pathology. Page 28 of 38

Fig. 22: Axial CECT of the same 65 yo patient with AIP following steroid treatment demonstrating resolution of pseudotumors. Page 29 of 38

Fig. 23: Axial CECT in a 59 yo man with AIP and biliary dilatation. Note the dilated intra and extrahepatic ducts as well as the degree of wall thickening and enhancement. Page 30 of 38

Fig. 24: Axial CECT in a 59 yo man with AIP and biliary dilatation. Note the degree of circumferential wall thickening and enhancement (arrow). A biliary stent is in situ. Page 31 of 38

Fig. 25: ERCP image from the same 59 yo male with presumed PSC. The CBD has been cannulated and is moderately dilated. The intrahepatic ducts appear strictured peripherally (arrow). Cytologic brushings revealed a diagnosis of autoimmune pancreatitis rather than the expected PSC. Page 32 of 38

Fig. 26: Axial CECT in a 57 yo male with AIP. The prostate is diffusely enlarged, heterogeneously hypodense, there is periprostatic fat stranding. Interval improvement after steroid treatment helped aid diagnosis. Page 33 of 38

Fig. 27: Color doppler transverse image of enlarged lymph nodes in the submandibular region. USS guided fine needle aspiration(fna) revealed abundant IgG4 bearing plasma cells. Page 34 of 38

Fig. 28: Grayscale image of only the left parotid gland (although bilateral parotid gland involvement) which has a heterogeneous appearance containing multiple hypoechoic nodules. FNA proven IgG4 rich plasma cells were found in the specimen. Page 35 of 38

Fig. 29: Color doppler image of only the left parotid gland which has an heterogeneous appearance containing multiple hypoechoic nodules. FNA proven IgG4 rich plasma cells were found in the specimen. Page 36 of 38

Conclusion AIP is a clinical entity frequently recognized in the radiology community. Patients often present with obstructive jaundice and can be misdiagnosed with pancreatic cancer. It is important to recognize this disorder, its extra-pancreatic processes and promptly commence steroid therapy to avoid end stage pancreatic disease and surgery. A multimodality imaging approach can support a clinical and biochemically suspected diagnosis. References 1. Yoshida K, Toki F, Takeuchi T, Watanabe S, Shiratori K, Hayashi N. Chronic pancreatitis caused by autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 1995; 40: 1561-8. 2. Fujinaga Y, Kadoya M, Kawa S et. al. Characteristic findings in images of extra-pancreatic lesions association with autoimmune pancreatitis. Eur J Radiol. 2010; 76: 228-238. 3. Bodily KD, Takahashi N, Fletcher JG et. al. Autoimmune pancreatitis: Pancreatic and extrapancreatic imaging findings. AJR. 2009; 192:431-437. 4. Wook KS, Suk K, Woo JL et al. Evaluation of unusual causes of pancreatitis: role of cross-sectional imaging. Eur J Radiol. 2009; 296-312. 5. Manfredi R, Graziani R, Cicero C et. al. Autoimmune pancreatitis: CT patterns and their changes after steroid treatment. Radiology. 2008; 247(2): 435-443. 6. Sahani DV, Sainani NI, Deshpande V et al. Autoimmune pancreatitis: disease evolution, staging, response assessment, and CT features that predict response to corticosteroid therapy. Radiology. 2009; 250 (1): 118-129. 7. Shandhogue AKP, Fasih N, Surabhi VR et. al. A clinical and radiologic review of uncommon types and causes of pancreatitis. Radiology. 2009;29:1003-1026. 8. Sunnapwa A, Prasad S, Menias C. Nonalcoholic, nonbiliary pancreatitis: cross sectional imaging spectrum. AJR. 2010;195:67-75. 9. Takahashi N, Fletcher JG, Hough DM. Autoimmune pancreatitis: differentiation from pancreatic carcinoma and normal pancreas on the Basis of Enhancement Characteristic at Dual phase CT. AJR. 2009;193:479-484. 10. Takahashi N, Kawashima A, Fletcher JG, Chari ST. Renal involvement in patients with autoimmune pancreatitis: CT and MR imaging findings. Radiology. 2007;242(3): 791-801. 11. Vlachou A, Khalili K, Hyun-Jung J, Fischer S, Hirschfield G, Tae Kyoung K. IgG4 related sclerosing disease. Autoimmune pancreatitis and extrpancreatic manifestations. Radiographics. 2011; 31: 1379-1402. Page 37 of 38

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