Type 2 Autoimmune Pancreatitis: A Challenge in the Differential Diagnosis of a Pancreatic Mass

Transcription

1 Clinicl Cse Study GE Port J Gstroenterol 2017;24: Received: October 10, 2016 Accepted fter revision: Februry 3, 2017 Published online: Mrch 23, 2017 Type 2 Autoimmune Pncretitis: A Chllenge in the Differentil Dignosis of Pncretic Mss Cláudio Mrtins Pul Lgo c Pul Sous b Trcísio Arújo c José Dvide d, e Fernndo Cstro-Poçs c e Isbel Pedroto c, e Deprtment of Gstroenterology, Centro Hospitlr de Setúbl Hospitl de São Bernrdo, Setúbl, b Deprtment of Gstroenterology, Centro Hospitlr Tondel-Viseu Hospitl de São Teotónio, Viseu, nd c Deprtment of Gstroenterology, nd d Heptobiliopncretic Unit, Centro Hospitlr do Porto Hospitl Gerl de Snto António, nd e Institute of Biomedicl Sciences Abel Slzr, University of Porto, Porto, Portugl Keywords Autoimmune pncretitis Immunoglobulin G4 Pncretic cncer Abstrct Introduction: Autoimmune pncretitis is rre entity of unknown etiology tht cn mimic pncretic cncer nd whose dignosis involves clinicl, serologicl, imgiologicl, nd histologicl findings. There re two types of utoimmune pncretitis: type 1, in which the pncres is involved s one prt of systemic immunoglobulin G4-relted disese, nd type 2, generlly without immunoglobulin G4-positive cells nd without systemic involvement. Cse: We report the cse of 45-yer-old femle, who underwent n bdominl mgnetic resonnce imging for etiologicl study of solid liver lesion, which reveled til pncretic mss. Lbortory nlyses showed norml levels of immunoglobulin G4 nd negtive ntinucler ntibodies. Endoscopic ultrsound reveled homogeneous nd hypoechogenic lesion in the pncretic til with susge-like ppernce. Endoscopic ultrsound-guided fine needle spirtion ws inconclusive nd the ptient underwent lproscopic distl pncretectomy. Histopthology exmintion confirmed the dignosis of type 2 utoimmune pncretitis. Conclusion: This cse highlights the chllenge in the dignostic pproch of pncretic mss, prticulrly in distinguishing benign from mlignnt disese. Published by S. Krger AG, Bsel Pncretite Autoimune Tipo 2: Desfio no Dignóstico Diferencil de um Mss Pncreátic Plvrs Chve Pncretite utoimune Imunoglobulin G4 Cncro pncreático Resumo Introdução: A pncretite utoimune é um entidde rr, de etioptogeni desconhecid, que pode simulr cncro do pâncres e cujo dignóstico envolve integrção de ddos clínicos, serológicos, imgiológicos e histológicos. Descrevem-se dois tipos de pncretite utoimune: tipo 1, cujo envolvimento pncreático integr o espe- E-Mil krger@krger.com Published by S. Krger AG, Bsel This rticle is licensed under the Cretive Commons Attribution- NonCommercil-NoDerivtives 4.0 Interntionl License (CC BY- NC-ND) ( Usge nd distribution for commercil purposes s well s ny distribution of modified mteril requires written permission. Dr. Cláudio Mrtins Deprtment of Gstroenterology, Centro Hospitlr de Setúbl Hospitl de São Bernrdo, Ru Cmilo Cstelo Brnco PT Setúbl (Portugl) E-Mil cmpus.ul.pt

2 tro ds doençs ssocids à imunoglobulin G4, e tipo 2, gerlmente sem evidênci de céluls imunoglobulin G4 positivs e sem mnifestções sistémics. Cso: Apresentmos o cso de um mulher de 45 nos, submetid ressonânci mgnétic bdominl pr esclrecimento etiológico de lesão nodulr hepátic que revelou um mss n cud do pâncres. Anliticmente presentv imunoglobulin G4 norml e nticorpos ntinucleres negtivos. A ultrssonogrfi endoscópic revelou um lesão homogéne e hipoecogénic n cud pncreátic com morfologi em slsich. A punção spirtiv por gulh fin foi inconclusiv tendo doente sido submetid pncretectomi distl por vi lproscópic. O exme histoptológico confirmou o dignóstico de pncretite utoimune tipo 2. Conclusão: Este cso destc o desfio n bordgem dignóstic d mss pncreátic, prticulrmente n diferencição entre ptologi benign e mlign. Introduction Publicdo por S. Krger AG, Bsel Autoimmune pncretitis (AIP) is fibro-inflmmtory disese tht ccounts for 4.6 5% of chronic pncretitis nd comprises two entities, currently designted s type 1 nd type 2, which hve unique histopthologicl ptterns nd differ significntly in their demogrphic profiles, clinicl presenttion, nd nturl history [1, 2]. Type 1 hs been recognized s the pncretic mnifesttion of multiorgn disese, nmed immunoglobulin G4 (IgG4)-relted disese, while type 2 is pncretic specific disorder not ssocited with IgG4. The dignostic criteri for AIP re combintion of imgiologicl, lbortoril, nd histopthologicl findings. Interntionl criteri for the dignosis of AIP hve been defined, such s the HISORt (histology, imging, elevted serum IgG4 levels, other orgn involvement, nd response to steroids) criteri [3] from the Myo Clinic nd, most recently, Interntionl Consensus Dignostic Criteri from Interntionl Assocition of Pncretology [4]. Despite this, the definitive dignosis of AIP, prticulrly type 2, is chllenging, s this disorder commonly presents s pncretic mss mimicking pncretic cncer. Misdignosis hs the potentil to be ctstrophic s n undignosed cncer my cuse dely or loss of the opportunity for potentil curtive surgery. The opposite scenrio of pncretic surgery performed for benign disese, with its high risk of morbidity nd mortlity, is lso unstisfctory. Herein, we report n uncommon cse of type 2 AIP presented s pncretic mss illustrting the chllenge in the differentil dignosis between AIP nd pncretic cncer. Cse Report A 45-yer-old Cucsin femle underwent n bdominl mgnetic resonnce imging (MRI) for etiologicl study of solid liver lesion (focl nodulr hyperplsi), detected on routine bdominl ultrsound, which reveled til pncretic solid lesion of undetermined etiology. She hd medicl history of rteril hypertension nd ulcertive colitis treted with bisoprolol nd meslzine. She reported no history of smoking or lcohol consumption. There ws no evidence of fever, jundice, bdominl pin, norexi, weight loss, or other gstrointestinl symptoms. Physicl exmintion ws unremrkble. Lbortory nlysis reveled no nemi nd liver tests, mylse, lipse, C rective-protein, erythrocyte sedimenttion rte, CA 19-9, nd IgG4 were norml. Antinucler ntibodies were negtive. In order to clrify the nture of the referred lesion, n endoscopic ultrsound (EUS) ws performed, which reveled homogeneous nd hypoechogenic lesion, with 40 mm of greter dimeter, in the pncretic til with susge-like ppernce ( Fig. 1 ). This lesion showed no vsculr pttern on Doppler exmintion ( Fig. 1 b). There were no pncretic clcifictions nd common biliry duct, pncretic duct, nd splenoportl xis were norml. An EUS-guided fine needle spirtion (FNA) with 19-guge needle ws performed ( Fig. 1 c), whose cytologicl nlysis showed bundnt inflmmtory infiltrte nd ductl epithelium with mild to moderte typi, pprently rective ( Fig. 1 d). Given tht the pncretic denocrcinom hypothesis could not be excluded, the ptient underwent lproscopic distl pncretectomy. Histopthology exmintion confirmed the dignosis of type 2 utoimmune pncretitis ( Fig. 2 ). At the 6-month follow-up, the ptient remined symptomtic with no evidence of recurrence. Discussion A rre form of idiopthic chronic pncretitis ws first described in 1961 by Srles et l. [5]. The term utoimmune pncretitis ws introduced by Yoshid et l. [6] in 1995 to describe steroid-responsive disese ssocited with utoimmune fetures. In 2009, two subtypes of AIP, clled type 1 (lymphoplsmcytic sclerosing pncretitis) nd type 2 (idiopthic duct-centric pncretitis), were formlly recognized [1, 2]. AIP is rre disorder, with reported prevlence in Jpn of 0.82/100,000. Concerning subtypes, type 1 is the most prevlent worldwide while type 2 is more common in Europe nd North Americ. In n interntionl study of 1,064 ptients, the verge ge t the time of dignosis ws 61.4 nd 39.9 yers for types 1 nd 2, respectively, Type 2 Autoimmune Pncretitis GE Port J Gstroenterol 2017;24:

3 b Fig. 1. Endosonogrphic nd cytologicl findings. Endoscopic ultrsound reveled homogeneous nd hypoechoic lesion with susge-like ppernce in the pncretic til ( ) with no vsculr pttern on Doppler exmintion ( b ). Endoscopic ultrsound-guided fine needle spirtion ( c ). Clusters of ductl cells with moderte typi on cytology ( d ) (H&E; 200). c d b Fig. 2. Histopthologicl fetures. c Dense lymphoplsmocytic nd grnulocytic infiltrtion within epithelium nd lumen ducts (grnulocytic epithelil lesion), oblitertive phlebitis, fibrosis, nd cinr trophy (H&E; 20; b 40; c 200). d Rre immunoglobulin G4-positive cells on immunohistochemistry (IHC; 40). c d 298 GE Port J Gstroenterol 2017;24: Mrtins/Lgo/Sous/Arújo/Dvide/ Cstro-Poçs/Pedroto

4 with proportion of mle ptients significntly higher in type 1 (77 vs. 55%) [7]. The clinicl picture of AIP depends on its subtype. Type 1 is more prevlent mong older mles nd belongs to the IgG4-relted systemic disese, which is ssocited with high serum nd/or tissue IgG4 nd other utoimmune disorders, including IgG4 cholngitis, sclerosing sildenitis, interstitil nephritis, nd retroperitonel fibrosis. The clssic clinicl presenttion in type 1 is pinless obstructive jundice (up to 75% of cses) mimicking pncretic cncer. Other clinicl fetures include chronic or recurrent bdominl pin (68%), cute pncretitis, nd stetorrhe. On the other hnd, type 2 AIP ffects minly younger ptients, without gender predilection, nd often is not ssocited with hyper-igg4. As in type 1, type 2 lso frequently presents with obstructive jundice (50% of cses) but without systemic involvement, except for inflmmtory bowel disese which is present in bout 30% of cses, prticulrly ulcertive colitis [8]. Overll, the pncretic disese in ptients with AIP cn present in different wys including (1) focl mss or diffuse enlrgement on imging tht cn be confused with pncretic cncer (85% of cses), (2) mild bdominl pin with or without cute or chronic pncretitis, (3) strictures of the pncretic duct, nd (4) peripncretic vsculr complictions (23%) [9]. We report cse of solid pncretic mss incidentlly detected on bdominl MRI in n symptomtic young femle ptient with history of ulcertive colitis. Dignosis of AIP is chllenging, prticulrly in type 2. Correct dignosis cn help vert the consequences of progressive disese nd unnecessry surgery. In the lst decde, severl dignostic criteri were proposed including clinicl, serologicl, imgiologicl, nd histologicl findings. In order to unify the heterogeneity of dignostic criteri, multintionl group convened in 2011 nd developed Interntionl Consensus Dignostic Criteri for AIP [4]. Due to its bility to provide high-resolution imging, EUS emerged s n importnt dignostic tool. Most common endosonogrphic findings re focl or diffuse susge-shped pncretic enlrgement, homogeneous echo pttern, strnding, nd clcifictions. A long nd/or multiple strictures of the pncretic duct, without significnt ssocited diltion, is lso highly chrcteristic of AIP. The other dvntge of EUS is the possibility to perform FNA or core biopsy, which provides tissue smples for cytologicl or histologicl dignosis. Despite the poor sensitivity (up to 37.5%) nd specificity of EUSguided FNA, the recent dvent of spring-loded biopsy needles provides high dignostic ccurcy (bout 85%) [10, 11]. Elstogrphy nd contrst-enhnced EUS re newer noninvsive technologies tht my help differentite benign from mlignnt solid pncretic lesions. Although both of these techniques my increse the dignostic yield of EUS, there re considerble number of issues tht remin to be solved, requiring dditionl studies. The definitive dignosis of type 2 AIP lwys requires histology, reveling n idiopthic duct-centric pncretitis, the hllmrks of which re grnulocytic epithelil lesions. IgG4 plsm cells re bsent or in smll number. Oblitertive phlebitis nd fibrosis re less prominent thn in type 1 [1, 2]. Unlike other forms of pncretitis, AIP is highly responsive to steroid therpy [13]. The dignosis of AIP should be reconsidered in ptients who do not respond to steroids. The relpse rte in ptients with type 1 AIP rnges from 30 60%, while ptients with type 2 typiclly do not relpse (<5%) [14]. Immunosuppressors, such s zthioprine or mycophenolte mofetil, re used in ptients with relpse or steroid-resistnt disese. Spontneous remission is seen in 24 55% of ptients [12, 13]. In spite of this, erly steroid therpy is recommended becuse, if untreted, the pncretic nd biliry disese cn progress to irreversible pncretic insufficiency nd secondry biliry cirrhosis. In this cse, the ptient underwent EUS nd the ultrsonogrphic fetures were suggestive of AIP. Although the clinicl, lbortory, nd imging findings fvor the dignosis of utoimmune pncretitis, the hypothesis of pncretic cncer could not be completely excluded due to the presence of moderte ductl typi on cytology. Therefore, the cse ws discussed t multidisciplinry meeting, nd, in order to definitively rule out more ominous lesion, surgicl pproch ws decided, llowing definitive dignosis. In conclusion, this report describes n uncommon entity highlighting the chllenge in the dignostic pproch of pncretic mss. Although the diffuse form of AIP cn be esily distinguished from pncretic cncer on imging, differentiting focl AIP from pncretic mlignncy is chllenging, like in the presented cse. Mking the correct dignosis nd differentiting AIP from pncretic cncer is of the utmost importnce; n greed dignostic pthwy should be in plce nd multidisciplinry pproch tken with ech ptient. Type 2 Autoimmune Pncretitis GE Port J Gstroenterol 2017;24:

5 Sttement of Ethics This study did not require informed consent nor review/pprovl by the pproprite ethics committee. Disclosure Sttement The uthors declre no conflicts of interest. References 1 Kloppel G, Detlefsen S, Chri ST, et l: Autoimmune pncretitis: the clinicopthologicl chrcteristics of the subtype with grnulocytic epithelil lesions. J Gstroenterol 2010; 45: Zhng L, Chri ST, Smyrk TC, et l: Autoimmune pncretitis (AIP) type 1 nd type 2: n interntionl consensus study on histopthologic dignostic criteri. Pncres 2011; 40: Chri ST, Smyrk TC, Levy MJ, et l: Dignosis of utoimmune pncretitis: the Myo Clinic experience. Clin Gstroenterol Heptol 2006; 4: Shimosegw T, Chri ST, Frulloni L, et l: Interntionl consensus dignostic criteri for utoimmune pncretitis: guidelines of the Interntionl Assocition of Pncretology. Pncres 2011; 40: Srles H, Srles JC, Murtore R, et l: Chronic inflmmtory sclerosis of the pncres n utonomous pncretic disese. Am J Dig Dis 1961; 6: Yoshid K, Toki F, Tkeuchi T, et l: Chronic pncretitis cused by n utoimmune bnormlity. Proposl of the concept of utoimmune pncretitis. Dig Dis Sci 1995; 40: Hrt PA, Kmisw T, Brugge WR, et l: Long-term outcomes of utoimmune pncretitis: multicentre, interntionl nlysis. Gut 2013; 62: Kmisw T, Chri ST, Lerch MM, et l: Recent dvnces in utoimmune pncretitis: type 1 nd type 2. Gut 2013; 62: Rin A, Ydv D, Krsinsks AM, et l: Evlution nd mngement of utoimmune pncretitis: experience t lrge US center. Am J Gstroenterol 2009; 104: Mizuno N, Bhti V, Hosod W, et l: Histologicl dignosis of utoimmune pncretitis using EUS-guided trucut biopsy: comprison study with EUS-FNA. J Gstroenterol 2009; 44: Knno A, Ishid K, Hmd S, et l: Dignosis of utoimmune pncretitis by EUS-FNA by using 22-guge needle bsed on the Interntionl Consensus Dignostic Criteri. Gstrointest Endosc 2012; 76: Kmisw T, Shimosegw T, Okzki K, et l: Stndrd steroid tretment for utoimmune pncretitis. Gut 2009; 58: Sh RP, Chri ST, Pnnl R, et l: Differences in clinicl profile nd relpse rte of type 1 versus type 2 utoimmune pncretitis. Gstroenterology 2010; 139: Ketwroo GA, Sheth S: Autoimmune pncretitis. Gstroenterol Rep (Oxf) 2013; 1: GE Port J Gstroenterol 2017;24: Mrtins/Lgo/Sous/Arújo/Dvide/ Cstro-Poçs/Pedroto