Differentiation of focal autoimmune pancreatitis from pancreatic ductal adenocarcinoma

  • Camila Lopes Vendrami
  • Joon Soo Shin
  • Nancy A. Hammond
  • Kunal Kothari
  • Pardeep K. Mittal
  • Frank H. MillerEmail author
Special Section: Pancreatitis


Autoimmune pancreatitis (AIP) is an inflammatory process of the pancreas that occurs most commonly in elderly males and clinically can mimic pancreatic adenocarcinoma and present with jaundice, weight loss, and abdominal pain. Mass-forming lesions in the pancreas are seen in the focal form of AIP and both clinical and imaging findings can overlap those of pancreatic cancer. The accurate distinction of AIP from pancreatic cancer is of utmost importance as it means avoiding unnecessary surgery in AIP cases or inaccurate steroid treatment in patients with pancreatic cancer. Imaging concomitantly with serological examinations (IgG4 and Ca 19-9) plays an important role in the distinction between these entities. Characteristic extra-pancreatic manifestations as well as favorable good response to treatment with steroids are characteristic of AIP. This paper will review current diagnostic parameters useful in differentiating between focal AIP and pancreatic adenocarcinoma.


Pancreatic adenocarcinoma Pancreatitis Autoimmune pancreatitis Chronic pancreatitis Computed tomography Magnetic resonance imaging 



No funding or grant support was used in the preparing of this manuscript.


  1. 1.
    Cao Z, Tian R, Zhang T, Zhao Y (2015) Localized autoimmune pancreatitis: report of a case clinically mimicking pancreatic cancer and a literature review. Medicine (Baltimore) 94 (42):e1656. Google Scholar
  2. 2.
    Kim KP, Kim MH, Song MH, Lee SS, Seo DW, Lee SK (2004) Autoimmune chronic pancreatitis. Am J Gastroenterol 99 (8):1605-1616. Google Scholar
  3. 3.
    Hoshimoto S, Aiura K, Tanaka M, Shito M, Kakefuda T, Sugiura H (2016) Mass-forming type 1 autoimmune pancreatitis mimicking pancreatic cancer. J Dig Dis 17 (3):202-209. Google Scholar
  4. 4.
    Hart PA, Zen Y, Chari ST (2015) Recent advances in autoimmune pancreatitis. Gastroenterology 149 (1):39-51. Google Scholar
  5. 5.
    Madhani K, Farrell JJ (2016) Autoimmune pancreatitis: an update on diagnosis and management. Gastroenterol Clin North Am 45 (1):29-43. Google Scholar
  6. 6.
    Khandelwal A, Shanbhogue AK, Takahashi N, Sandrasegaran K, Prasad SR (2014) Recent advances in the diagnosis and management of autoimmune pancreatitis. AJR Am J Roentgenol 202 (5):1007-1021. Google Scholar
  7. 7.
    Muhi A, Ichikawa T, Motosugi U, Sou H, Sano K, Tsukamoto T, Fatima Z, Araki T (2012) Mass-forming autoimmune pancreatitis and pancreatic carcinoma: differential diagnosis on the basis of computed tomography and magnetic resonance cholangiopancreatography, and diffusion-weighted imaging findings. Journal of magnetic resonance imaging: JMRI 35 (4):827-836. Google Scholar
  8. 8.
    Al-Hawary MM, Kaza RK, Azar SF, Ruma JA, Francis IR (2013) Mimics of pancreatic ductal adenocarcinoma. Cancer Imaging 13 (3):342-349. Google Scholar
  9. 9.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67 (1):7-30. Google Scholar
  10. 10.
    Lee H, Lee JK, Kang SS, Choi D, Jang KT, Kim JH, Lee KT, Paik SW, Yoo BC, Rhee JC (2007) Is there any clinical or radiologic feature as a preoperative marker for differentiating mass-forming pancreatitis from early-stage pancreatic adenocarcinoma? Hepatogastroenterology 54 (79):2134-2140Google Scholar
  11. 11.
    de Pretis N, Amodio A, Frulloni L (2018) Updates in the field of autoimmune pancreatitis: a clinical guide. Expert Rev Gastroenterol Hepatol 12 (7):705-709. Google Scholar
  12. 12.
    Sugumar A, Chari ST (2009) Distinguishing pancreatic cancer from autoimmune pancreatitis: a comparison of two strategies. Clin Gastroenterol Hepatol 7 (11 Suppl):S59-62. Google Scholar
  13. 13.
    Church NI, Pereira SP, Deheragoda MG, Sandanayake N, Amin Z, Lees WR, Gillams A, Rodriguez-Justo M, Novelli M, Seward EW, Hatfield AR, Webster GJ (2007) Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series. Am J Gastroenterol 102 (11):2417-2425. Google Scholar
  14. 14.
    Notohara K, Burgart LJ, Yadav D, Chari S, Smyrk TC (2003) Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases. The American journal of surgical pathology 27 (8):1119-1127Google Scholar
  15. 15.
    Kamisawa T, Takuma K, Anjiki H, Egawa N, Hata T, Kurata M, Honda G, Tsuruta K, Suzuki M, Kamata N, Sasaki T (2010) Differentiation of autoimmune pancreatitis from pancreatic cancer by diffusion-weighted MRI. Am J Gastroenterol 105 (8):1870-1875. Google Scholar
  16. 16.
    Kamisawa T, Imai M, Yui Chen P, Tu Y, Egawa N, Tsuruta K, Okamoto A, Suzuki M, Kamata N (2008) Strategy for differentiating autoimmune pancreatitis from pancreatic cancer. Pancreas 37 (3):e62-67. Google Scholar
  17. 17.
    Chang MC, Liang PC, Jan S, Yang CY, Tien YW, Wei SC, Wong JM, Chang YT (2014) Increase diagnostic accuracy in differentiating focal type autoimmune pancreatitis from pancreatic cancer with combined serum IgG4 and CA19-9 levels. Pancreatology: official journal of the International Association of Pancreatology (IAP) [et al] 14 (5):366-372.
  18. 18.
    Naitoh I, Nakazawa T, Hayashi K, Okumura F, Miyabe K, Shimizu S, Kondo H, Yoshida M, Yamashita H, Ohara H, Joh T (2012) Clinical differences between mass-forming autoimmune pancreatitis and pancreatic cancer. Scand J Gastroenterol 47 (5):607-613. Google Scholar
  19. 19.
    Finkelberg DL, Sahani D, Deshpande V, Brugge WR (2006) Autoimmune pancreatitis. The New England journal of medicine 355 (25):2670-2676. Google Scholar
  20. 20.
    van Heerde MJ, Buijs J, Hansen BE, de Waart M, van Eijck CH, Kazemier G, Pek CJ, Poley JW, Bruno MJ, Kuipers EJ, van Buuren HR (2014) Serum level of Ca 19-9 increases ability of IgG4 test to distinguish patients with autoimmune pancreatitis from those with pancreatic carcinoma. Digestive diseases and sciences 59 (6):1322-1329. Google Scholar
  21. 21.
    Ghazale A, Chari ST, Smyrk TC, Levy MJ, Topazian MD, Takahashi N, Clain JE, Pearson RK, Pelaez-Luna M, Petersen BT, Vege SS, Farnell MB (2007) Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer. Am J Gastroenterol 102 (8):1646-1653. Google Scholar
  22. 22.
    Raina A, Krasinskas AM, Greer JB, Lamb J, Fink E, Moser AJ, Zeh HJ, 3rd, Slivka A, Whitcomb DC (2008) Serum immunoglobulin G fraction 4 levels in pancreatic cancer: elevations not associated with autoimmune pancreatitis. Archives of pathology & laboratory medicine 132 (1):48-53.;2
  23. 23.
    Pak LM, Schattner MA, Balachandran V, D’Angelica MI, DeMatteo RP, Kingham TP, Jarnagin WR, Allen PJ (2018) The clinical utility of immunoglobulin G4 in the evaluation of autoimmune pancreatitis and pancreatic adenocarcinoma. HPB: the official journal of the International Hepato Pancreato Biliary Association 20 (2):182-187. Google Scholar
  24. 24.
    Goonetilleke KS, Siriwardena AK (2007) Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 33 (3):266-270. Google Scholar
  25. 25.
    Chari ST, Takahashi N, Levy MJ, Smyrk TC, Clain JE, Pearson RK, Petersen BT, Topazian MA, Vege SS (2009) A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol 7 (10):1097-1103. Google Scholar
  26. 26.
    Parra JL, Kaplan S, Barkin JS (2005) Elevated CA 19-9 caused by Hashimoto’s thyroiditis: review of the benign causes of increased CA 19-9 level. Digestive diseases and sciences 50 (4):694-695Google Scholar
  27. 27.
    Kodama T, Satoh H, Ishikawa H, Ohtsuka M (2007) Serum levels of CA19-9 in patients with nonmalignant respiratory diseases. Journal of clinical laboratory analysis 21 (2):103-106. Google Scholar
  28. 28.
    Kim HR, Lee CH, Kim YW, Han SK, Shim YS, Yim JJ (2009) Increased CA 19-9 level in patients without malignant disease. Clinical chemistry and laboratory medicine 47 (6):750-754. Google Scholar
  29. 29.
    La Greca G, Sofia M, Lombardo R, Latteri S, Ricotta A, Puleo S, Russello D (2012) Adjusting CA19-9 values to predict malignancy in obstructive jaundice: influence of bilirubin and C-reactive protein. World journal of gastroenterology 18 (31):4150-4155. Google Scholar
  30. 30.
    Steinberg W (1990) The clinical utility of the CA 19-9 tumor-associated antigen. Am J Gastroenterol 85 (4):350-355Google Scholar
  31. 31.
    Jefferis R (2005) Glycosylation of recombinant antibody therapeutics. Biotechnology progress 21 (1):11-16. Google Scholar
  32. 32.
    Arnold JN, Wormald MR, Sim RB, Rudd PM, Dwek RA (2007) The impact of glycosylation on the biological function and structure of human immunoglobulins. Annual review of immunology 25:21-50. Google Scholar
  33. 33.
    Dall’Olio F, Vanhooren V, Chen CC, Slagboom PE, Wuhrer M, Franceschi C (2013) N-glycomic biomarkers of biological aging and longevity: a link with inflammaging. Ageing research reviews 12 (2):685-698. Google Scholar
  34. 34.
    Chen G, Li H, Qiu L, Qin X, Liu H, Li Z (2014) Change of fucosylated IgG2 Fc-glycoforms in pancreatitis and pancreatic adenocarcinoma: a promising disease-classification model. Analytical and bioanalytical chemistry 406 (1):267-273. Google Scholar
  35. 35.
    Smyk DS, Rigopoulou EI, Koutsoumpas AL, Kriese S, Burroughs AK, Bogdanos DP (2012) Autoantibodies in autoimmune pancreatitis. International journal of rheumatology 2012:940831. Google Scholar
  36. 36.
    Savides TJ, Donohue M, Hunt G, Al-Haddad M, Aslanian H, Ben-Menachem T, Chen VK, Coyle W, Deutsch J, DeWitt J, Dhawan M, Eckardt A, Eloubeidi M, Esker A, Gordon SR, Gress F, Ikenberry S, Joyce AM, Klapman J, Lo S, Maluf-Filho F, Nickl N, Singh V, Wills J, Behling C (2007) EUS-guided FNA diagnostic yield of malignancy in solid pancreatic masses: a benchmark for quality performance measurement. Gastrointestinal endoscopy 66 (2):277-282. Google Scholar
  37. 37.
    Gress F, Gottlieb K, Sherman S, Lehman G (2001) Endoscopic ultrasonography-guided fine-needle aspiration biopsy of suspected pancreatic cancer. Annals of internal medicine 134 (6):459-464Google Scholar
  38. 38.
    Fritscher-Ravens A, Brand L, Knofel WT, Bobrowski C, Topalidis T, Thonke F, de Werth A, Soehendra N (2002) Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis. Am J Gastroenterol 97 (11):2768-2775. Google Scholar
  39. 39.
    Wiersema MJ, Levy MJ, Harewood GC, Vazquez-Sequeiros E, Jondal ML, Wiersema LM (2002) Initial experience with EUS-guided trucut needle biopsies of perigastric organs. Gastrointestinal endoscopy 56 (2):275-278Google Scholar
  40. 40.
    Levy MJ, Jondal ML, Clain J, Wiersema MJ (2003) Preliminary experience with an EUS-guided trucut biopsy needle compared with EUS-guided FNA. Gastrointestinal endoscopy 57 (1):101-106. Google Scholar
  41. 41.
    Fujinaga Y, Kadoya M, Kawa S, Hamano H, Ueda K, Momose M, Kawakami S, Yamazaki S, Hatta T, Sugiyama Y (2010) Characteristic findings in images of extra-pancreatic lesions associated with autoimmune pancreatitis. Eur J Radiol 76 (2):228-238. Google Scholar
  42. 42.
    Kamisawa T, Chari ST, Lerch MM, Kim MH, Gress TM, Shimosegawa T (2013) Recent advances in autoimmune pancreatitis: type 1 and type 2. Gut 62 (9):1373-1380. Google Scholar
  43. 43.
    Manfredi R, Frulloni L, Mantovani W, Bonatti M, Graziani R, Pozzi Mucelli R (2011) Autoimmune pancreatitis: pancreatic and extrapancreatic MR imaging-MR cholangiopancreatography findings at diagnosis, after steroid therapy, and at recurrence. Radiology 260 (2):428-436. Google Scholar
  44. 44.
    Agrawal S, Daruwala C, Khurana J (2012) Distinguishing autoimmune pancreatitis from pancreaticobiliary cancers: current strategy. Ann Surg 255 (2):248-258. Google Scholar
  45. 45.
    Hafezi-Nejad N, Singh VK, Fung C, Takahashi N, Zaheer A (2018) MR imaging of autoimmune pancreatitis. Magn Reson Imaging Clin N Am 26 (3):463-478. Google Scholar
  46. 46.
    Naitoh I, Nakazawa T, Ohara H, Ando T, Hayashi K, Tanaka H, Okumura F, Miyabe K, Yoshida M, Sano H, Takada H, Joh T (2010) Clinical significance of extrapancreatic lesions in autoimmune pancreatitis. Pancreas 39 (1):e1-5. Google Scholar
  47. 47.
    Furuhashi N, Suzuki K, Sakurai Y, Ikeda M, Kawai Y, Naganawa S (2015) Differentiation of focal-type autoimmune pancreatitis from pancreatic carcinoma: assessment by multiphase contrast-enhanced CT. Eur Radiol 25 (5):1366-1374. Google Scholar
  48. 48.
    Kozoriz MG, Chandler TM, Patel R, Zwirewich CV, Harris AC (2015) Pancreatic and extrapancreatic features in autoimmune pancreatitis. Can Assoc Radiol J 66 (3):252-258. Google Scholar
  49. 49.
    Wakabayashi T, Kawaura Y, Satomura Y, Watanabe H, Motoo Y, Okai T, Sawabu N (2003) Clinical and imaging features of autoimmune pancreatitis with focal pancreatic swelling or mass formation: comparison with so-called tumor-forming pancreatitis and pancreatic carcinoma. Am J Gastroenterol 98 (12):2679-2687. Google Scholar
  50. 50.
    Takahashi N, Fletcher JG, Hough DM, Fidler JL, Kawashima A, Mandrekar JN, Chari ST (2009) Autoimmune pancreatitis: differentiation from pancreatic carcinoma and normal pancreas on the basis of enhancement characteristics at dual-phase CT. AJR Am J Roentgenol 193 (2):479-484. Google Scholar
  51. 51.
    Sun GF, Zuo CJ, Shao CW, Wang JH, Zhang J (2013) Focal autoimmune pancreatitis: radiological characteristics help to distinguish from pancreatic cancer. World J Gastroenterol 19 (23):3634-3641. Google Scholar
  52. 52.
    Lee-Felker SA, Felker ER, Kadell B, Farrell J, Raman SS, Sayre J, Lu DS (2015) Use of MDCT to differentiate autoimmune pancreatitis from ductal adenocarcinoma and interstitial pancreatitis. AJR Am J Roentgenol 205 (1):2-9. Google Scholar
  53. 53.
    Chang WI, Kim BJ, Lee JK, Kang P, Lee KH, Lee KT, Rhee JC, Jang KT, Choi SH, Choi DW, Choi DI, Lim JH (2009) The clinical and radiological characteristics of focal mass-forming autoimmune pancreatitis: comparison with chronic pancreatitis and pancreatic cancer. Pancreas 38 (4):401-408. Google Scholar
  54. 54.
    Ryan DP, Hong TS, Bardeesy N (2014) Pancreatic adenocarcinoma. N Engl J Med 371 (22):2140-2141. Google Scholar
  55. 55.
    Al-Hawary MM, Francis IR, Chari ST, Fishman EK, Hough DM, Lu DS, Macari M, Megibow AJ, Miller FH, Mortele KJ, Merchant NB, Minter RM, Tamm EP, Sahani DV, Simeone DM (2014) Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the Society of Abdominal Radiology and the American Pancreatic Association. Radiology 270 (1):248-260. Google Scholar
  56. 56.
    Gardner TB, Chari ST (2008) Autoimmune pancreatitis. Gastroenterol Clin North Am 37 (2):439-460, vii.
  57. 57.
    Sugiyama Y, Fujinaga Y, Kadoya M, Ueda K, Kurozumi M, Hamano H, Kawa S (2012) Characteristic magnetic resonance features of focal autoimmune pancreatitis useful for differentiation from pancreatic cancer. Jpn J Radiol 30 (4):296-309. Google Scholar
  58. 58.
    Hur BY, Lee JM, Lee JE, Park JY, Kim SJ, Joo I, Shin CI, Baek JH, Kim JH, Han JK, Choi BI (2012) Magnetic resonance imaging findings of the mass-forming type of autoimmune pancreatitis: comparison with pancreatic adenocarcinoma. Journal of magnetic resonance imaging: JMRI 36 (1):188-197. Google Scholar
  59. 59.
    Choi SY, Kim SH, Kang TW, Song KD, Park HJ, Choi YH (2016) Differentiating mass-forming autoimmune pancreatitis from pancreatic ductal adenocarcinoma on the basis of contrast-enhanced MRI and DWI findings. AJR Am J Roentgenol 206 (2):291-300. Google Scholar
  60. 60.
    Kim HJ, Kim YK, Jeong WK, Lee WJ, Choi D (2015) Pancreatic duct “icicle sign” on MRI for distinguishing autoimmune pancreatitis from pancreatic ductal adenocarcinoma in the proximal pancreas. Eur Radiol 25 (6):1551-1560. Google Scholar
  61. 61.
    Carbognin G, Girardi V, Biasiutti C, Camera L, Manfredi R, Frulloni L, Hermans JJ, Mucelli RP (2009) Autoimmune pancreatitis: imaging findings on contrast-enhanced MR, MRCP and dynamic secretin-enhanced MRCP. Radiol Med 114 (8):1214-1231. Google Scholar
  62. 62.
    Nishino T, Oyama H, Toki F, Shiratori K (2010) Differentiation between autoimmune pancreatitis and pancreatic carcinoma based on endoscopic retrograde cholangiopancreatography findings. J Gastroenterol 45 (9):988-996. Google Scholar
  63. 63.
    Kamisawa T, Tu Y, Egawa N, Tsuruta K, Okamoto A, Kodama M, Kamata N (2009) Can MRCP replace ERCP for the diagnosis of autoimmune pancreatitis? Abdom Imaging 34 (3):381-384. Google Scholar
  64. 64.
    Negrelli R, Manfredi R, Pedrinolla B, Boninsegna E, Ventriglia A, Mehrabi S, Frulloni L, Pozzi Mucelli R (2015) Pancreatic duct abnormalities in focal autoimmune pancreatitis: MR/MRCP imaging findings. Eur Radiol 25 (2):359-367. Google Scholar
  65. 65.
    Zhang J, Jia G, Zuo C, Jia N, Wang H (2017) (18)F- FDG PET/CT helps differentiate autoimmune pancreatitis from pancreatic cancer. BMC Cancer 17 (1):695. Google Scholar
  66. 66.
    Lee TY, Kim MH, Park DH, Seo DW, Lee SK, Kim JS, Lee KT (2009) Utility of 18F-FDG PET/CT for differentiation of autoimmune pancreatitis with atypical pancreatic imaging findings from pancreatic cancer. AJR Am J Roentgenol 193 (2):343-348. Google Scholar
  67. 67.
    Ozaki Y, Oguchi K, Hamano H, Arakura N, Muraki T, Kiyosawa K, Momose M, Kadoya M, Miyata K, Aizawa T, Kawa S (2008) Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography. J Gastroenterol 43 (2):144-151. Google Scholar
  68. 68.
    Cho MK, Moon SH, Song TJ, Kim RE, Oh DW, Park DH, Lee SS, Seo DW, Lee SK, Kim MH (2018) Contrast-enhanced endoscopic ultrasound for differentially diagnosing autoimmune pancreatitis and pancreatic cancer. Gut Liver 12 (5):591-596. Google Scholar
  69. 69.
    Miller FH, Rini NJ, Keppke AL (2006) MRI of adenocarcinoma of the pancreas. AJR Am J Roentgenol 187 (4):W365-374. Google Scholar
  70. 70.
    Vlachou PA, Khalili K, Jang HJ, Fischer S, Hirschfield GM, Kim TK (2011) IgG4-related sclerosing disease: autoimmune pancreatitis and extrapancreatic manifestations. Radiographics 31 (5):1379-1402. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiology, Northwestern Memorial HospitalNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Department of Radiology and ImagingMedical College of GeorgiaAugustaUSA

Personalised recommendations