Type 1 autoimmune pancreatitis (AIP1) is an IgG4-related systemic disease that mimics tumors. We report a rare case of AIP1 accompanied by mucinous cystic neoplasm (MCN). A pancreatic lesion was incidentally detected in a woman in her 60s. After 6 years of follow-up, the lesion abruptly increased in size. Computed tomography showed a 3.5 cm unilocular cyst in the tail of the pancreas and distal pancreatectomy was performed. On microscopic examination, the cyst was lined by mucinous and non-mucinous epithelial cells with mild cytologic atypia. The surrounding stroma comprised ovarian-type spindle cells with progesterone receptor positivity. The pericystic pancreas exhibited multifocal lymphoid follicles, lymphoplasmacytic infiltrations, obliterative phlebitis, and storiform fibrosis. IgG4-positive plasma cell infiltration (215 cells high-power field) and the IgG4/IgG ratio (57%) were increased. Cases of MCN coexisting with AIP1 are extremely rare; only two such cases have been reported in the English-language literature. This third case featured low-grade MCN with AIP1

Hyoung Jung Kim

Mee-Jeong Kim

Myung-Hwan Kim

Seung-Mo Hong

Song-Cheol Kim

Tae Jun Song

Journal of Pathology and Translational Medicine

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125© 2019 The Korean Society of Pathologists/The Korean Society for CytopathologyThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/ by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.pISSN 2383-7837eISSN 2383-7845Journal of Pathology and Translational Medicine 2019; 53: 125-128https://doi.org/10.4132/jptm.2018.10.25▒ CASE STUDY ▒Mucinous cystic neoplasms (MCNs) of the pancreas are cyst-forming and composed of columnar mucinous epithelia with varying degrees of cytologic atypia.1 Traditionally, MCNs have been classified as low-, intermediate-, or high-grade dysplasia according to the degree of cytological atypia.1 Recently, however, the Baltimore consensus meeting proposed a two-tiered system for pancreatic precursor lesions, including MCNs and intraductal papillary mucinous neoplasms (IPMNs), classifying them as either low-grade (which includes the previous low- and intermediate-grade dysplasia) or high-grade.2 MCNs are histologically recog-nizable precursor lesions of pancreatic ductal adenocarcinomas.3 They are associated with ovarian-type stroma and do not com-municate with the pancreatic ductal system, which are diagnostic differential points with IPMNs.4 The majority of MCNs occur in women aged 40–60 years at the time of diagnosis.1 The body and tail of the pancreas are the most common locations for MCNs; involvement of the head is rare.1Autoimmune pancreatitis (AIP) is a type of chronic pancre-atitis that presents with obstructive jaundice and/or a pancreatic mass, with histologic features of dense lymphoplasmacytic infil-trations and fibrosis; it responds well to steroid treatment.5 AIP is classified as types 1 and 2. The diagnostic criteria for type 1 AIP (AIP1) are well established by international consensus and include clinical, serological, imaging, and pathology components.6 The characteristic histologic features of AIP1 are dense lym-phoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis.7 A diagnosis of AIP1 is made based on the number of these histologic features observed and the number of IgG4-posi-tive plasma cell infiltrations seen in high-power fields (> 50 cells for surgical resection or > 10 cells for biopsy specimens).7There have been several case reports about AIP1 accompanied by other pancreatic lesions, such as a pseudocyst or IPMN.8-11 However, MCN with AIP1 is extremely rare and only two cases have been reported in the English-language literature.12,13 Here, we report a third case, a patient with both low-grade MCN and AIP1.Coexisting Mucinous Cystic Neoplasm of the Pancreas and Type 1 Autoimmune PancreatitisMee-Jeong Kim · Tae Jun Song1 Hyoung Jung Kim2 · Song-Cheol Kim3 Myung-Hwan Kim1 Seung-Mo Hong Departments of Pathology and 1Gastroenterology, 2Department of Radiology and Research Institute of Radiology, 3Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaType 1 autoimmune pancreatitis (AIP1) is an IgG4-related systemic disease that mimics tumors. We report a rare case of AIP1 accompanied by mucinous cystic neoplasm (MCN). A pancreatic lesion was incidentally detected in a woman in her 60s. After 6 years of follow-up, the lesion abruptly increased in size. Computed tomography showed a 3.5 cm unilocular cyst in the tail of the pancreas and distal pancreatectomy was performed. On microscopic examination, the cyst was lined by mucinous and non-mucinous epithelial cells with mild cytologic atypia. The surround-ing stroma comprised ovarian-type spindle cells with progesterone receptor positivity. The pericystic pancreas exhibited multifocal lymphoid follicles, lymphoplasmacytic infiltrations, obliterative phlebitis, and storiform fibrosis. IgG4-positive plasma cell infiltration (215 cells high-power field) and the IgG4/IgG ratio (57%) were increased. Cases of MCN coexisting with AIP1 are extremely rare; only two such cases have been reported in the English-language literature. This third case featured low-grade MCN with AIP1.Key Words: Pancreas; Mucinous cystic neoplasm; Autoimmune pancreatitisReceived: October 1, 2018Revised: October 17, 2018Accepted: October 24, 2018Corresponding AuthorSeung-Mo Hong, MD, PhDDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, KoreaTel: +82-2-3010-4558Fax: +82-2-472-7898E-mail: smhong28@gmail.comhttp://jpatholtm.org/ https://doi.org/10.4132/jptm.2018.10.25126     •  Kim MJ et al.CASE REPORTA woman in her 60s admitted our hospital with a symptom-less, incidentally detected pancreatic cystic lesion. Initial com-puted tomography (CT) imaging revealed a 2.2 cm unilocular cystic pancreas lesion in the body and tail of the pancreas with-out accompanying wall enhancement and with no mural nodule. There was no evidence of narrowing of the main pancreatic duct or of acute pancreatitis (Fig. 1A). The initial laboratory findings were unremarkable, including normal levels of γ-GT (13 IU/L; normal range, 5 to 36 IU/L), amylase (65 U/L; normal range, 30 to 110 U/L), and lipase (37 U/L; normal range, 13 to 60 U/L). Suspecting either a pseudocyst or MCN, the patient was regularly followed up. After 6 years of follow-up, the cystic lesion had increased in size to 3.5 cm (Fig. 1B). As a result, the patient underwent a distal pancreatectomy. On gross examination, a 3.5 cm-sized unilocular cyst was observed in the body and tail of the pancreas. The cyst wall was irregularly thickened, firm, and fibrotic (Fig. 1C). The inner surface of the cyst was yellowish white and rough, with multifocal hemorrhagic spots. The cyst contained sticky mucinous fluid. The remaining pancreatic parenchyma away from the cystic neoplasm was unremarkable, and there was no dilatation of the main pancreatic duct.Low-power magnification images revealed that the cystic wall was surrounded by dense spindle cell clusters, with numerous lymphoid follicles observed in a fibrotic background (Fig. 1D). The thin sections of the cyst wall were lined by a single layer of epithelial cells that were mostly non-mucinous or focally mucinous (Fig. 1E). The epithelial cells were pseudostratified without showing pleomorphism or prominent nucleoli, and the surround-ing dense spindle cells were closely packed, showing ovarian-type spindle cells. Nuclear progesterone receptor labeling showed these spindle cells to be dense (Fig. 1F). The irregularly thick-ened portions of the cyst wall observed in the gross examination contained multiple lymphoid follicles in a background of chronic inflammatory cell infiltrations, predominantly lymphoplasma-cytic (Fig. 1G). Some areas contained dense periductal lympho-plasmacytic infiltrations (Fig. 1H). Several foci of obliterative Fig. 1. (A) Coronal contrast-enhanced computed tomography image showing a unilocular cyst in the pancreas tail. (B) Six years later, the cyst had grown, with its longest diameter increasing from 2.2 to 3.5 cm, as well as thickening of the cyst wall (arrowheads). (C) The unilocu-lar cyst in the body and tail of the pancreas showing irregular thickening of the cyst wall. (D) Scanning power image showing lymphoid folli-cles and lymphoplasmacytic infiltration around the cyst wall. (E) The cyst wall was lined mostly by non-mucinous and focally mucinous epi-thelial cells with mild cytologic atypia. (F) Progesterone receptor nuclear labeling highlighted ovarian-type stromal cells. (G) The irregularly thickened cyst wall contained multiple lymphoid follicles in a background of chronic inflammatory cell infiltrations. (H) Some areas showed dense periductal lymphoplasmacytic infiltrations. (I, J) Several foci of obliterative phlebitis were noted by hematoxylin and eosin staining (I) and elastic staining (J). (K, L) Areas of dense lymphoplasmacytic infiltrations (K) showed numerous IgG4-positive plasma cell infiltrations (L).AEIBFJCGKDHLhttp://jpatholtm.org/https://doi.org/10.4132/jptm.2018.10.25Type 1 AIP with Pancreatic MCN  •     127phlebitis were revealed by H&E and elastic staining (Fig. 1I, J). Areas of dense lymphoplasmacytic infiltrations (Fig. 1K) in-cluded numerous IgG4-positive plasma cell infiltrations (Fig. 1L). As many as 215 IgG4-positive plasma cells were observed in the most active area. The IgG4/ IgG ratio was about 57%. Serum IgG4 measured 6 days after the distal pancreatectomy was within the normal range (0.4 mg/dL). The patient was diag-nosed with low-grade MCN associated with AIP1.All procedures performed in the current study were approved by Institutional Review Board approval (approval No. 2018-1160) for waiver of the informed consent in accordance with the 1964 Helsinki declaration and its later amendments.DISCUSSIONMCN is a precursor lesion of pancreatic ductal adenocarcino-mas, whereas AIP is a tumor mimicker. This case was interesting because the patient underwent distal pancreatectomy after the MCN increased in size. In addition to low-grade MCN, we ob-served features of AIP1 in the irregularly thickened periphery of the cyst wall. This case exhibited a range of histologic features considered to be pathologic diagnostic criteria of AIP1,7 including lymphoplasmacytic infiltration, stromal storiform fibrosis, and obliterative phlebitis, along with > 50 IgG4-positive plasma cell infiltrations (with up to 215 IgG4-positive plasma cells observed). Thus, this case was histologically highly suggestive of AIP1.However, other histologic, imaging and serologic features con-sistent with AIP1, such as diffuse pancreatic enlargement and pancreatic ductal strictures without significant ductal dilata-tion, were not observed in the present case. The patient’s serum IgG4 level 6 days postoperatively was not significantly elevated.It is rare for the histologic features of AIP1 to be reported in association with pancreatic cystic lesions, including IPMNs and pseudocysts. All the reported cases exhibited the histologic fea-tures of AIP1; in addition, some cases showed increased serum IgG4 levels,8,9,11 whereas another did not.10 There has been only one English-language report of a case of MCN accompanied by the histologic features of AIP1, and that case had an elevated se-rum IgG4 level.12In the present case, the histologic features of AIP1 were observed in a limited area, the periphery of the cyst wall, and did not extend into the surrounding pancreatic parenchyma. With the normal pancreatic ductal system observed on radiologic imaging, these features can be interpreted as indicating a localized form of AIP1. Similar features were reported in the previous case.12 Comparisons of clinicopathologic characteristics of MCN in association with AIP1 with previously reported cases and the present case are summarized in Table 1.The pathogenesis of AIP1 in association with MCN is not fully understood. The most plausible explanation is the co-exis-tence of two lesions, the AIP1 and the MCN.13 Other possibili-ties include a secondary inflammatory response to a pre-existing MCN due to the use of fine needle aspiration biopsy or cytology of the MCN for histologic confirmation, or a secondary immune reaction of the periphery of the cyst wall of the pancreas to in-spissated extracellular mucin from the MCN.12In summary, we report a case of low-grade MCN coexisting with AIP1. This case exceptionally demonstrated the presence of both a cystic tumor and a tumor mimicker in the same pancreas.ORCIDMee-Jeong Kim: https://orcid.org/0000-0001-7466-7586Tae Jun Song: https://orcid.org/0000-0002-6156-8746Hyoung Jung Kim: https://orcid.org/0000-0003-3391-5621Song-Cheol Kim: https://orcid.org/0000-0003-4552-4169Myung-Hwan Kim: https://orcid.org/0000-0003-0992-6734Seung-Mo Hong: https://orcid.org/0000-0002-8888-6007Author Contributions Conceptualization: SMH.Data curation: MJK, SCK, MHK.Formal analysis: TJS, HJK, SMH.Investigation: MJK, SMH.Validation: MJK, SMH.Visualization: MJK, HJK, SMH.Writing—original draft: MJK, SMH.Writing—review & editing: MJK, HJK, SMH.Table 1. Comparisons of clinicopathologic characteristics of MCN in association with AIP1 with previously reported casesStudy Age (yr) Sex Dysplasia Fibrosis Obliterative phlebitis IgG4+plasma cells/HPF IgG4/IgG (%) Serum IgG4 level (mg/dL)Yakirevich et al.12 33 Female High-grade  Storiform Present 75 42 97.5DiCarlo et al.13 26 Female Low-grade  Dense band Present 160 NA NAPresent case 60 Female Low-grade  Storiform Present 215 57 0.4aMCN, mucinous cystic neoplasm; AIP1, type 1 autoimmune pancreatitis; NA, not applicable; HPF, high-power field.aSampled on postoperative day 6.http://jpatholtm.org/ https://doi.org/10.4132/jptm.2018.10.25128     •  Kim MJ et al.Conflicts of InterestThe authors declare that they have no potential conflicts of interest.AcknowledgmentsThis study was funded by a grant (1320200) from National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea.REFERENCES1. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classifica-tion of tumours of the digestive system. 4th ed. Lyon: International Agency for Research on Cancer, 2010.2. Basturk O, Hong SM, Wood LD, et al. A revised classification system and recommendations from the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas. Am J Surg Pathol 2015; 39: 1730-41.3. Hong SM, Park JY, Hruban RH, Goggins M. Molecular signatures of pancreatic cancer. Arch Pathol Lab Med 2011; 135: 716-27.4. Hruban RH, Pitman MB, Klimstra DS. AFIP atlas of tumor patholo-gy, series IV. Tumors of the pancreas. Washington, DC: Armed Forces Institute of Pathology, 2007.5. Hart PA, Zen Y, Chari ST. Recent advances in autoimmune pancre-atitis. Gastroenterology 2015; 149: 39-51.6. Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas 2011; 40: 352-8.7. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012; 25: 1181-92.8. Gompertz M, Morales C, Aldana H, Castillo J, Berger Z. Cystic lesions in autoimmune pancreatitis. Case Rep Gastroenterol 2015; 9: 366-74.9. Nakaji S, Hirata N, Fujii H, et al. A case of focal autoimmune pan-creatitis (AIP) mimicking an intraductal papillary mucinous neo-plasm (IPMN). Clin J Gastroenterol 2013; 6: 329-33.10. Urata T, Naito Y, Izumi Y, et al. Localized type 1 autoimmune pan-creatitis superimposed upon preexisting intraductal papillary mu-cinous neoplasms. World J Gastroenterol 2013; 19: 9127-32.11. Vaquero EC, Salcedo MT, Cuatrecasas M, et al. Autoimmune pan-creatitis type-1 associated with intraduct papillary mucinous neo-plasm: report of two cases. Pancreatology 2014; 14: 316-8.12. Yakirevich E, Henriksen KJ, Miner T, Resnick MB. Mucinous cystic neoplasm of the pancreas with increased IgG4+ plasma cells and histopathologic features of autoimmune pancreatitis/IgG4-related disease. Pancreas 2015; 44: 674-6.13. DiCarlo C, Silverman J, Bunker M. Type 1 autoimmune pancreatitis associated with mucinous cystic neoplasm. Am J Clin Pathol 2016; 146(Suppl 1): 290 .

Coexisting Mucinous Cystic Neoplasm of the Pancreas and Type 1 Autoimmune Pancreatitis

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Coexisting Mucinous Cystic Neoplasm of the Pancreas and Type 1 Autoimmune Pancreatitis

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