Pyloric, pseudopyloric, and spasmolytic polypeptide-expressing metaplasias in autoimmune gastritis: a case series of 22 Japanese patients

Yasuhiro Wada, Shigemi Nakajima, Ryoji Kushima, Shizuki Takemura, Naoko Mori, Hiroshi Hasegawa, Takahisa Nakayama, Ken-Ichi Mukaisho, Akiko Yoshida, Shinji Umano, Kazuo Yamamoto, Hiroyuki Sugihara, Kazunari Murakami, Yasuhiro Wada, Shigemi Nakajima, Ryoji Kushima, Shizuki Takemura, Naoko Mori, Hiroshi Hasegawa, Takahisa Nakayama, Ken-Ichi Mukaisho, Akiko Yoshida, Shinji Umano, Kazuo Yamamoto, Hiroyuki Sugihara, Kazunari Murakami

Abstract

There are two types of pyloric gland-like metaplasia in the corpus of stomach: pyloric and pseudopyloric metaplasias. They show the same morphology as the original pyloric glands in H&E staining. Pseudopyloric metaplasia is positive for pepsinogen (PG) I immunohistochemically, whereas pyloric metaplasia is negative. Recently, spasmolytic polypeptide-expressing metaplasia (SPEM) is proposed for pyloric gland-like metaplasia mainly in animal experiments. SPEM expresses trefoil factor family 2 (TFF2) and is often considered synonymous with pseudopyloric metaplasia. We reviewed consecutive 22 Japanese patients with autoimmune gastritis (AIG) to investigate TFF2 expression in pyloric and pseudopyloric metaplasias by counting all pyloric gland-like glands in biopsy specimens taken from greater curvature of the middle corpus according to the Updated Sydney System. Pyloric metaplasia was seen in all the 22 cases, and pseudopyloric metaplasia was found in 15 cases. Of 1567 pyloric gland-like glands in all the cases, 1381 (88.1%) glands were pyloric metaplasia glands, and the remaining 186 (11.9%) glands were pseudopyloric metaplasia glands. TFF2 expression was observed in pyloric or pseudopyloric metaplasia glands in 20 cases. TFF2 expression was recognized in 409 of 1381 (26.9%) pyloric metaplasia glands and 27 of 186 (14.5%) pseudopyloric metaplasia glands (P<0.01, chi-square test). In conclusion, SPEM was not always the same as pseudopyloric metaplasia in human AIG, and the majority of metaplasia in AIG was not pseudopyloric but pyloric metaplasia.

Keywords: Autoimmune gastritis; Gastrin; Pseudopyloric metaplasia; Spasmolytic polypeptide-expressing metaplasia.

Conflict of interest statement

The authors declare that they have no conflict of interest.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Light microscopic pictures of the typical AIG cases in florid and end stages (H&E stain, low (a, c) and high (b, d) power magnifications). In the florid stage, the parietal cells are extensively reduced and persistent inflammation is observed (a). Parietal cells are under destruction (b: arrow). In the end stage, parietal cells are completely lost and inflammatory cell infiltrates are reduced (c). Pyloric-like glands are seen in the bottom of the mucosa (d). Scale bar: 200μm
Fig. 2
Fig. 2
Light microscopic pictures of the typical AIG cases with H&E (a, c, e) and immunohistochemical stainings with anti- H+/K+-ATPase (b, h), anti-Chromogranin A (d), anti-BCL-10 (f) and anti-α-amylase (g). Parietal cells are significantly reduced in the oxyntic mucosa in a case of florid stage (a, b). ECL cell hyperplasia is recognized in the corpus mucosa in linear (black arrowhead) and nodular types (red arrowhead) in a case of florid stage (c, d). Pancreatic acinar cell metaplasia is found in the oxyntic mucosa of a case in end stage which showed BCL-10 positive (f black arrow), α-amylase vague (g red arrow), and H+/K+-ATPase negative (h). Scale bar 200μm
Fig. 3
Fig. 3
Light microscopic pictures for gastrin cells in serial sectioned slides in the antrum (a, b) and corpus (c, d) in typical AIG cases: H&E (a, c) and immunohistochemical staining with anti-gastrin (b, d). Gastrin-positive cells are recognized in the pyloric glands in the antrum (b). Gastrin-positive cells are also seen in the pyloric gland-like metaplasia glands in the corpus (d). The intensity of gastrin staining is weak in the corpus compared with that in the antrum. Scale bar: 200μm
Fig. 4
Fig. 4
Light microscopic pictures of the four types of metaplasias in the serially sectioned slides: H&E (left pictures) and immunohistochemical stainings with anti-MUC6, PGI, and TFF2 (right 3 pictures). There were four types of glands in immunohistochemical stainings with anti-PGI and TFF2: PGI-/TFF2+ (a), PGI−/TFF2− (b), PGI+/TFF2+ (c), PGI+/TFF2− (d). Scale bar 200μm

References

    1. Vinay K, Abul KA, Nelson F, Richard NM. Robbins basic pathology. 8. Philadelphia: Saunders Elsevier; 2007.
    1. Hattori T, Helpap B, Gedigk P. The morphology and cell kinetics of pseudopyloric glands. Cell Pathol. 1982;39:31–40.
    1. Solcia E, Capella C, Fiocca R, Cornaggia M, Rindi G, Villani L, Bosi F, Ambrosiani L. Exocrine and endocrine epithelial changes in types A and B chronic gastritis. In: Malfertheiner P, Ditschuneit H, editors. Helicobacter pylori, Gastritis and Peptic Ulcer. Berlin: Springer-Verlag; 1990. pp. 245–258.
    1. Wada Y, Kushima R, Kodama M, Fukuda M, Fukuda K, Okamoto K, Ogawa R, Mizukami K, Okimoto T, Murakami K. Histological changes associated with pyloric and pseudopyloric metaplasia after Helicobacter pylori eradication. Virchows Arch. 2020;477:489–496. doi: 10.1007/s00428-020-02805-9.
    1. Krishnamurthy S, Dayal Y. Pancreatic metaplasia in Barrett's esophagus. An immunohistochemical study. Am J Surg Pathol. 1995;19:1172–1180. doi: 10.1097/00000478-199510000-00007.
    1. Johansson J, Håkansson HO, Mellblom L, Kempas A, Kjellén G, Brudin L, Granath F, Johansson KE, Nyrén O. Pancreatic acinar metaplasia in the distal oesophagus and the gastric cardia: prevalence, predictors and relation to GORD. J Gastroenterol. 2010;45:291–299. doi: 10.1007/s00535-009-0161-4.
    1. Schneider NI, Plieschnegger W, Geppert M, Wigginghaus B, Höss GM, Eherer A, Wolf EM, Rehak P, Vieth M, Langner C. Pancreatic acinar cells--a normal finding at the gastroesophageal junction? Data from a prospective Central European multicenter study. Virchows Arch. 2013;463:643–650. doi: 10.1007/s00428-013-1471-8.
    1. Wang TC, Goldenring JR, Dangler C, Ito S, Mueller A, Jeon WK, Koh TJ, Fox JG. Mice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacter felis infection. Gastroenterology. 1998;114:675–689. doi: 10.1016/S0016-5085(98)70581-5.
    1. Schmidt PH, Lee JR, Joshi V, Playford RJ, Poulsom R, Wright NA, Goldenring JR. Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab Investig. 1999;79:639–646.
    1. Goldenring JR, Nam KT. Oxyntic atrophy, metaplasia, and gastric cancer. Prog Mol Biol Transl Sci. 2010;96:117–131. doi: 10.1016/B978-0-12-381280-3.00005-1.
    1. Hu GY, Yu BP, Dong WG, Li MQ, Yu JP, Luo HS, Rang ZX. Expression of TFF2 and Helicobacter pylori infection in carcinogenesis of gastric mucosa. World J Gastroenterol. 2003;9:910–914. doi: 10.3748/wjg.v9.i5.910.
    1. Halldórsdóttir AM, Sigurdardóttrir M, Jónasson JG, Oddsdóttir M, Magnússon J, Lee JR, Goldenring JR. Spasmolytic polypeptide-expressing metaplasia (SPEM) associated with gastric cancer in Iceland. Dig Dis Sci. 2003;48:431–441. doi: 10.1023/A:1022564027468.
    1. Yoshizawa N, Takenaka Y, Yamaguchi H, Tsukamoto T, Tanaka H, Tatematsu M, Nomura S, Goldenring JR, Kaminishi M. Emergence of spasmolytic polypeptide-expressing metaplasia in Mongolian gerbils infected with Helicobacter pylori. Lab Investig. 2007;87:1265–1276. doi: 10.1038/labinvest.3700682.
    1. Nam KT, O'Neal RL, Coffey RJ, Finke PE, Barker M, Goldenring JR. Spasmolytic polypeptide-expressing metaplasia (SPEM) in the gastric oxyntic mucosa does not arise from Lgr5-expressing cells. Gut. 2012;61:1678–1685. doi: 10.1136/gutjnl-2011-301193.
    1. Graham DY, Zou WY. Guilt by association: intestinal metaplasia does not progress to gastric cancer. Curr Opin Gastroenterol. 2018;34:458–464. doi: 10.1097/MOG.0000000000000472.
    1. Goldenring JR. Pyloric metaplasia, pseudopyloric metaplasia, ulcer-associated cell lineage and spasmolytic polypeptide-expressing metaplasia: reparative lineages in the gastrointestinal mucosa. J Pathol. 2018;245:132–137. doi: 10.1002/path.5066.
    1. Xia HH, Yang Y, Lam SK, Wong WM, Leung SY, Yuen ST, Elia G, Wright NA, Wong BC. Aberrant epithelial expression of trefoil family factor 2 and mucin 6 in Helicobacter pylori infected gastric antrum, incisura, and body and its association with antralisation. J Clin Pathol. 2004;57:861–866. doi: 10.1136/jcp.2003.015487.
    1. Fox JG, Rogers AB, Whary MT, Ge Z, Ohtani M, Jones EK, Wang TC. Accelerated progression of gastritis to dysplasia in the pyloric antrum of TFF2 -/- C57BL6 x Sv129 Helicobacter pylori-infected mice. Am J Pathol. 2007;171:1520–1528. doi: 10.2353/ajpath.2007.070249.
    1. Lennerz JK, Kim SH, Oates EL, Huh WJ, Doherty JM, Tian X, Bredemeyer AJ, Goldenring JR, Lauwers GY, Shin YK, Mills JC. The transcription factor MIST1 is a novel human gastric chief cell marker whose expression is lost in metaplasia, dysplasia, and carcinoma. Am J Pathol. 2010;177:1514–1533. doi: 10.2353/ajpath.2010.100328.
    1. Jin RU, Mills JC. Are gastric and esophageal metaplasia relatives? The case for Barrett’s stemming from SPEM. Dig Dis Sci. 2018;63:2028–2041. doi: 10.1007/s10620-018-5150-0.
    1. Strickland RG, Mackay IR. A reappraisal of the nature and significance of chronic atrophic gastritis. Am J Dig Dis. 1973;18:426–440. doi: 10.1007/BF01071995.
    1. Callaghan JM, Khan MA, Alderuccio F, Driel IR, Gleeson PA, Toh BH. Alpha and beta subunits of the gastric H+/K(+)-ATPase are concordantly targeted by parietal cell autoantibodies associated with autoimmune gastritis. Autoimmunity. 1993;16:289–295. doi: 10.3109/08916939309014648.
    1. Karlsson FA, Burman P, Lööf L, Mårdh S. Major parietal cell antigen in autoimmune gastritis with pernicious anemia is the acid-producing H+,K+-adenosine triphosphatase of the stomach. J Clin Invest. 1988;81:475–479. doi: 10.1172/JCI113344.
    1. Stolte M, Baumann K, Bethke B, Ritter M, Lauer E, Eidt H. Active autoimmune gastritis without total atrophy of the glands. Z Gastroenterol. 1992;30:729–735.
    1. Bettington M, Brown I. Autoimmune gastritis: novel clues to histological diagnosis. Pathology. 2013;45:145–149. doi: 10.1097/PAT.0b013e32835cc22c.
    1. Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis--pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013;10:529–541. doi: 10.1038/nrgastro.2013.101.
    1. Pittman ME, Voltaggio L, Bhaijee F, Robertson SA, Montgomery EA. Autoimmune metaplastic atrophic gastritis: recognizing precursor lesions for appropriate patient evaluation. Am J Surg Pathol. 2015;39:1611–1620. doi: 10.1097/PAS.0000000000000481.
    1. Kulnigg-Dabsch S. Autoimmune gastritis. Wien Med Wochenschr. 2016;166:424–430. doi: 10.1007/s10354-016-0515-5.
    1. Doglioni C, Laurino L, Dei Tos AP, Boni MD, Franzin G, Braidotti P, Viale G. Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases. Am J Surg Pathol. 1993;17:1134–1143. doi: 10.1097/00000478-199311000-00006.
    1. Jhala NC, Montemor M, Jhala D, Lu L, Talley L, Haber MM, Lechago J. Pancreatic acinar cell metaplasia in autoimmune gastritis. Arch Pathol Lab Med. 2003;127:854–857. doi: 10.5858/2003-127-854-PACMIA.
    1. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–1181. doi: 10.1097/00000478-199610000-00001.
    1. Greenson JK, Lawers GY, Montgomery EA, Owens SR, Polydorides AD. Diagnostic pathology; Gastrointestinal. 3. Amsterdam: Elsevier; 2019.
    1. Chlumská A, Boudová L, Benes Z, Zámecník M. Autoimmune gastritis. A clinicopathologic study of 25 cases. Cesk Patol. 2005;41:137–142.
    1. La Rosa S, Franzi F, Marchet S, Finzi G, Clerici M, Vigetti D, Chiaravalli AM, Sessa F, Capella C. The monoclonal anti-BCL10 antibody (clone 331.1) is a sensitive and specific marker of pancreatic acinar cell carcinoma and pancreatic metaplasia. Virchows Arch. 2009;454:133–142. doi: 10.1007/s00428-008-0710-x.
    1. Hosoda W, Sasaki E, Murakami Y, Yamao K, Shimizu Y, Yatabe Y. BCL10 as a useful marker for pancreatic acinar cell carcinoma, especially using endoscopic ultrasound cytology specimens. Pathol Int. 2013;63:176–182. doi: 10.1111/pin.12045.
    1. Jeong S, Choi E, Petersen CP, Roland JT, Federico A, Ippolito R, D'Armiento FP, Nardone G, Nagano O, Saya H, Romano M, Goldenring JR. Distinct metaplastic and inflammatory phenotypes in autoimmune and adenocarcinoma-associated chronic atrophic gastritis. United European Gastroenterol J. 2017;5:37–44. doi: 10.1177/2050640616644142.
    1. Kim J, Kim MJ, Kho HS. Oral manifestations in vitamin B12 deficiency patients with or without history of gastrectomy. BMC Oral Health. 2016;16:60. doi: 10.1186/s12903-016-0215-y.
    1. Kawanaka M, Tanikawa T, Kamada T, Ishii K, Urata N, Nakamura J, Nishino K, Suehiro M, Sasai T, Manabe N, Monobe Y, Kawamoto H, Haruma K. High prevalence of autoimmune gastritis in patients with nonalcoholic steatohepatitis. Intern Med. 2019;58:2907–2913. doi: 10.2169/internalmedicine.2693-19.

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