Роль морфологического исследования в диагностике хронического аутоиммунного гастрита: обзор литературы

Введение. В развитых странах наблюдается тенденция к снижению распространенности гастрита, ассоциированного с H. pylori, что ведет к увеличению относительной частоты хронического аутоиммунного гастрита в структуре поражений желудка при исследовании биопсийного материала. Наблюдаемые тенденции, а также предполагаемый недостаточный уровень диагностики аутоиммунного гастрита в России делают актуальным обсуждение принципов диагностики этого заболевания.
Цель работы — привести современные данные по критериям морфологической диагностики хронического аутоиммунного гастрита.
Материалы и методы. Поиск данных по проблеме осуществлен в базах научных публикаций PubMed, Web of Science, Scopus, eLibrary.ru. Глубина научного поиска составила 175 лет (1849–2024 гг.).
Результаты и обсуждение. Диагностика аутоиммунного гастрита сводится к эндоскопическому исследованию с забором биоптатов по диагностическому протоколу OLGA и модифицированной Сиднейской системе (антральный отдел, угол и тело желудка). При этом серологические методы (обнаружение специфических антител) не всегда позволяют подтвердить или опровергнуть диагноз, ввиду существования серонегативного варианта заболевания, что определяет первостепенную роль морфологического исследования. Постепенное разрушение париетальных клеток под действием аутоиммунного процесса приводит к широкому спектру морфологических изменений, которые проходят ряд стадий: от глубокой воспалительной инфильтрации области тела и дна желудка до тяжелой атрофии с различными вариантами метаплазии (прежде всего псевдопилорической). Практикующему патологоанатому важно уметь проводить дифференциальную диагностику аутоиммунного гастрита от H. pylori-ассоциированного гастрита, постхеликобактерного атрофического гастрита, особым диагностическим вызовом является сочетание H. pylori гастрита с аутоиммунным.
Заключение. Хронический аутоиммунный гастрит является диагнозом, в постановке которого участвуют гастроэнтеролог, эндоскопист, патологоанатом. Определена и обоснована ведущая роль морфологических методов в диагностике хронического аутоиммунного гастрита.

1. Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis — pathogenesis, pathology and management. Nature Reviews Gastroenterology and Hepatology. 2013;10(9):529–541. DOI: https://doi.org/10.1038/nrgastro.2013.101.

2. Khlynova RI, Khromtsova OM, Khlinov IB, Berdnikov RB, Petrov VM, Moroz GA, et al. Prevalence of Helicobacter pylori-associated diseases in the Ural Federal District. Ural Medical Journal. 2023;22(5):14–22. (In Russ.) DOI: https://doi.org/10.52420/2071-5943-2023-22-5-14-22.

3. Lenti MV, Rugge M, Lahner E, Miceli E, Toh BH, Genta RM, et al. Autoimmune gastritis. Nature Reviews Disease Primers. 2020;6(1):56. DOI: https://doi.org/10.1038/s41572-020-0187-8.

4. Rugge M, Bricca L, Guzzinati S, Sacchi, D, Pizzi M, Savarino E, et al. Autoimmune gastritis: Long-term natural history in naïve Helicobacter pylori-negative patients. Gut. 2023;72(1):30–38. DOI: https://doi.org/10.1136/gutjnl-2022-327827.

5. Rugge M, Genta RM, Malfertheiner P, Graham DY. Atrophic autoimmune gastritis: ‘A muddled or misguided core concept compromises our overall comprehension of the problem’. Gut. 2024;73(1):207–208. DOI: https://doi.org/10.1136/gutjnl-2022-329161.

6. Strickland RG, Mackay IR. A reappraisal of the nature and significance of chronic atrophic gastritis. The American Journal of Digestive Diseases. 1973;18(5):426–440. DOI: https://doi.org/10.1007/BF01071995.

7. Misiewicz JI. The Sydney System: A new classification of gastritis. Introduction. Journal of Gastroenterology and Hepatology. 1991;6(3):207–208. DOI: https://doi.org/10.1111/j.1440-1746.1991.tb01467.x.

8. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis: The updated Sydney system. The American Journal of Surgical Pathology. 1996;20(10):1161–1181. DOI: https://doi.org/10.1097/00000478-199610000-00001.

9. Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, et al. Kyoto global consensus report on Helicobacter pylorigastritis. Gut. 2015;64(9):1353–1367. DOI: https://doi.org/10.1136/gutjnl-2015-309252.

10. Coati I, Fassan M, Farinati F, Graham DY, Genta RM, Rugge M. Autoimmune gastritis: Pathologist’s viewpoint. World Journal of Gastroenterology. 2015;21(42):12179–12189. DOI: https://doi.org/10.3748/wjg.v21.i42.12179.

11. Livzan MA, Gaus OV, Mozgovoj SI, Bodunova NA, Yаnova TI, Polyakova VV, et al. Chronic Autoimmune Gastritis: Risk Factors, Clinical Manifestations and Diagnostic Principles. Effektivnaja Farmakoterapija. 2021;17(39):66–73. (In Russ.). DOI: https://doi.org/10.33978/2307-3586-2021-17-39-66-73.

12. Embutnieks YuV, Voynovan IN, Kolbasnikov SV, Bordin DS. Autoimmune gastritis: Pathogenesis, modern approaches to diagnosis and treatment. Pharmateca. 2017;S5:8–15. (In Russ.). EDN: https://elibrary.ru/zxaavz.

13. Mozgovoy SI, Kostenko MB, Krolevets TS, Livzan MA. Autoimmune gastritis in the focus of clinician and morphologist. Pharmateca. 2019;26(2):121–129. (In Russ.). DOI: https://doi.org/10.18565/pharmateca.2019.2.121-129.

14. Livzan MA, Gaus OV, Mozgovoi SI, Bordin DS. Chronic autoimmune gastritis: Modern diagnostic principles. Diagnostics. 2021;11(11):2113. DOI: https://doi.org/10.3390/diagnostics11112113.

15. Losik YA, Selivanova LS, Antonova TV, Lapina TL, Tertychny AS, Ivashkin VT. Morphological diagnostic criteria of autoimmune gastritis. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016; 26(5):13–20. (In Russ.). DOI: https://doi.org/10.22416/1382-4376-2016-5-13-20.

16. Losik YA, Selivanova LS, Konkov MY, Lapina TL, Tertychny AS, Ivashkin VT. Morphological features of autoimmune gastritis. Russian Journal of Gastroenterology, Hepatology, Coloproctolog. 2014;24(1):10–15. (In Russ.). EDN: https://elibrary.ru/sentlj.

17. Livzan MA, Krolevets TS, Mozgovoy SI, Kostoglod TV, Kostoglod AV. Autoimmune gastritis: from symptom to diagnosis. Clinical observations. Consilium Medicum. 2020;22(8):78–84. (In Russ.). DOI: https://doi.org/10.26442/20751753.2020.8.200037.

18. Krolevets TS, Livzan MA, Mozgovoy SI, Kostoglod TV, Kostoglod AV. Autoimmune gastritis in the practice of an internist: Series of clinical observations. Pharmateca. 2021;28(2):60–63. (In Russ.). DOI: https://doi.org/10.18565/pharmateca.2021.2.60-63.

19. Zhang H, Jin Z, Cui R, Ding S, Huang Y, Zhou L. Autoimmune metaplastic atrophic gastritis in chinese: A study of 320 patients at a large tertiary medical center. Scandinavian Journal of Gastroenterology. 2016; 52(2):150–156. DOI: https://doi.org/10.1080/00365521.2016.1236397.

20. Pittman ME, Voltaggio L, Bhaijee F, Robertson SA, Montgomery EA. Autoimmune Metaplastic Atrophic Gastritis. The American Journal of Surgical Pathology. 2015;39(12):1611–1620. DOI: https://doi.org/10.1097/pas.0000000000000481.

21. Miceli E, Lenti MV, Padula D, Luinetti O, Vattiato C, Monti CM, et al. Common features of patients with autoimmune atrophic gastritis. Clinical Gastroenterology and Hepatology. 2012;10(7):812–814. DOI: https://doi.org/10.1016/j.cgh.2012.02.018.

22. Notsu T, Adachi K, Mishiro T, Fujihara H, Toda T, Takaki S, et al. Prevalence of autoimmune gastritis in individuals undergoing medical checkups in Japan. Internal Medicine. 2019;58(13):1817–1823. DOI: https://doi.org/10.2169/internalmedicine.2292-18.

23. Wolf EM, Plieschnegger W, Geppert M, Wigginghaus B, Hoss GM, Eherer A, et al. Changing prevalence patterns in endoscopic and histological diagnosis of gastritis? Data from a cross-sectional Central European multicentre study. Digestive and Liver Disease. 2014;46(5):412–418. DOI: https://doi.org/10.1016/j.dld.2013.12.017.

24. Kulak O, Gurram B, Montgomery EA, Park JY. Pediatric autoimmune gastritis: clinical correlates and histologic features. Human Pathology. 2021;116:31–38. DOI: https://doi.org/10.1016/j.humpath.2021.07.002.

25. Toh BH. Diagnosis and classification of autoimmune gastritis. Autoimmunity Reviews. 2014;13(4–5):459–462. DOI: https://doi.org/10.1016/j.autrev.2014.01.048.

26. Rusak E, Chobot A, Krzywicka A, Wenzlau J. Anti-parietal cell antibodies — diagnostic significance. Advances in Medical Sciences. 2016;61(2):175–179. DOI: https://doi.org/10.1016/j.advms.2015.12.004.

27. Conti L, Lenti MV, Di Sabatino A, Miceli E, Galli G, Cazzato M, et al. Seronegative autoimmune atrophic gastritis is more common in elderly patients. Digestive and Liver Disease. 2020;52(11):1310–1314. DOI: https://doi.org/10.1016/j.dld.2020.04.015.

28. Lenti MV, Miceli E, Cococcia S, Klersy C, Staiani M, Guglielmi F, et al. Determinants of diagnostic delay in autoimmune atrophic gastritis. Alimentary Pharmacology & Therapeutics. 2019;50(2):167–175. DOI: https://doi.org/10.1111/apt.15317.

29. Lahner E, Spoletini M, Buzzetti R, Corleto VD, Vannella L, Petrone A, et al. HLA-DRB1*03 and DRB1*04 are associated with atrophic gastritis in an Italian population. Digestive and Liver Disease. 2010;42(12):854–859. DOI: https://doi.org/10.1016/j.dld.2010.04.011.

30. Oksanen AM, Haimila KE, Rautelin HI, Partanen JA. Immunogenetic characteristics of patients with autoimmune gastritis. World Journal of Gastroenterology. 2010;16 (3):354. DOI: https://doi.org/10.3748/wjg.v16.i3.354.

31. Hughes JW, Muegge BD, Tobin GS, Litvin M, Sun L, Saenz JB, et al. High-risk gastric pathology and prevalent autoimmune diseases in patients with pernicious anemia. Endocrine Practice. 2017;23(11):1297–1303. DOI: https://doi.org/10.4158/ep-2017-0056.

32. Bizzaro N, Antico A. Diagnosis and classification of pernicious anemia. Autoimmunity Reviews. 2014; 13(4–5):565–568. DOI: https://doi.org/10.1016/j.autrev.2014.01.042.

33. Toh BH, Gleeson PA, Simpson RJ, Moritz RL, Callaghan JM, Goldkorn I, et al. The 60-to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a beta subunit of the gastric H+/K (+)-ATPase (proton pump). Proceedings of the National Academy of Sciences. 1990;87(16):6418–6422. DOI: https://doi.org/10.1073/pnas.87.16.6418.

34. Gleeson PA, Toh BH. Molecular targets in pernicious anaemia. Immunology Today. 1991;12(7):233–238. DOI: https://doi.org/10.1016/0167-5699(91)90036-S.

35. Rugge M, Genta RM, Malfertheiner P, Dinis-Ribeiro M, El-Serag H, Graham DY, et al. RE.GA.IN.: The Real-world Gastritis Initiative — updating the updates. Gut. 2024;73(3):407–441. DOI: https://doi.org/10.1136/gutjnl-2023-331164.

36. Di Sabatino A, Lenti MV, Giuffrida P, Vanoli A, Corazza GR. New insights into immune mechanisms underlying autoimmune diseases of the gastrointestinal tract. Autoimmunity Reviews. 2015;14(12):1161–1169. DOI: https://doi.org/10.1016/j.autrev.2015.08.004.

37. Park JY, Lam-Himlin D, Vemulapalli R. Review of autoimmune metaplastic atrophic gastritis. Gastrointestinal Endoscopy. 2013;77(2):284–292. DOI: https://doi.org/10.1016/j.gie.2012.09.033.

38. Kamada T, Maruyama Y, Monobe Y, Haruma K. Endoscopic features and clinical importance of autoimmune gastritis. Digestive Endoscopy. 2021;34 (4):700–713. DOI: https://doi.org/10.1111/den.14175.

39. Khalaf K, Ching C, Wang T, Bechara R. White globe appearance in autoimmune atrophic gastritis. Journal of the Canadian Association of Gastroenterology. 2023;7(3):219–220. DOI: https://doi.org/10.1093/jcag/gwad050.

40. Iwamuro M, Tanaka T, Kanzaki H, Kawano S, Kawahara Y, Okada H, et al. Two cases of white globe appearance in autoimmune atrophic gastritis. Case Reports in Gastrointestinal Medicine. 2018;2018(1):7091520. DOI: https://doi.org/10.1155/2018/7091520.

41. Doyama H, Yoshida N, Tsuyama S, Ota R, Takeda Y, Nakanishi H, et al. The “white globe appearance” (WGA): A novel marker for a correct diagnosis of early gastric cancer by magnifying endoscopy with narrow-band imaging (M-NBI). Endoscopy International Open. 2015;03(02):E120–E124. DOI: https://doi.org/10.1055/s-0034-1391026.

42. Rugge M, Correa P, Di Mario F, El-Omar E, Fiocca R, Geboes K, et al. OLGA staging for gastritis: A tutorial. Digestive and Liver Disease. 2008;40(8):650–658. DOI: https://doi.org/10.1016/j.dld.2008.02.030.

43. Solcia E, Rindi G, Fiocca R, Villani L, Buffa R, Ambrosiani L, et al. Distinct patterns of chronic gastritis associated with carcinoid and cancer and their role in tumorigenesis. Yale Journal of Biology and Medicine. 1992;65(6):793–804. PMID: https://pubmed.gov/1341079.

44. Rugge M, Fassan M, Pizzi M, Zorzetto V, Maddalo G, Realdon S, et al. Autoimmune gastritis: Histology phenotype and OLGA staging. Alimentary Pharmacology & Therapeutics. 2012;35(12):1460–1466. DOI: https://doi.org/10.1111/j.1365-2036.2012.05101.x.

45. Wada Y, Kushima R, Kodama M, Fukuda M, Fukuda K, Okamoto K, et al. Histological changes associated with pyloric and pseudopyloric metaplasia after Helicobacter pylori eradication. Virchows Archiv. 2020; 477(4):489–496. DOI: https://doi.org/10.1007/s00428-020-02805-9.

46. Goldenring JR. Pyloric metaplasia, pseudopyloric metaplasia, ulcer-associated cell lineage and spasmolytic polypeptide-expressing metaplasia: Reparative lineages in the gastrointestinal mucosa. The Journal of Pathology. 2018;245(2):132–137. DOI: https://doi.org/10.1002/path.5066.

47. Wada Y, Nakajima S, Kushima R, Takemura S, Mori N, Hasegawa H, et al. Pyloric, pseudopyloric, and spasmolytic polypeptide-expressing metaplasias in autoimmune gastritis: A case series of 22 Japanese patients. Virchows Archiv. 2021;479(1):169–178. DOI: https://doi.org/10.1007/s00428-021-03033-5.

48. Schmidt PH, Lee JR, Joshi V, Playford RJ, Poulsom R, Wright NA. Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Laboratory Investigation. 1999;79(6):639–646. PMID: https://pubmed.gov/10378506.

49. Graham DY, Zou WY. Guilt by association: Intestinal metaplasia does not progress to gastric cancer. Current Opinion in Gastroenterology. 2018;34(6):458–464. DOI: https://doi.org/10.1097/mog.0000000000000472.

50. Goldenring J. No H. pylori, no adenocarcinoma for patients with autoimmune gastritis. Gut. 2023;72(1):1–2. DOI: https://doi.org/10.1136/gutjnl-2022-328068.

51. Stolte M, Baumann K, Bethke B, Ritter M, Lauer E, Eidt H. Active autoimmune gastritis without total atrophy of the glands. Zeitschrift fur Gastroenterologie. 1992;30(10):729–735. PMID: https://pubmed.gov/1441676.

52. Torbenson M, Abraham SC, Boitnott J, Yardley JH, Wu TT. Autoimmune gastritis: Distinct histological and immunohistochemical findings before complete loss of oxyntic glands. Modern Pathology. 2002; 15(2):102–109. DOI: https://doi.org/10.1038/modpathol.3880499.

53. Terao S, Suzuki S, Kushima R. Histopathologic diagnosis of ultra‐early autoimmune gastritis: A case report. Clinical Case Reports. 2023;11(6): e7458. DOI: https://doi.org/10.1002/ccr3.7458.

54. Hall SN, Appelman HD. Autoimmune gastritis. Archives of Pathology & Laboratory Medicine. 2019; 143(11):1327–1331. DOI: https://doi.org/10.5858/arpa.2019-0345-ra.

55. Mozgovoi SI, Livzan MA, Krolevets TS, Shimanskaya AG. Neuroendocrine tumour as a diagnostic and prognostic criterion for autoimmune gastritis. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(6):49–59. (In Russ.). DOI: https://doi.org/10.22416/1382-4376-2019-29-6-49-59.

56. Tertychnyy AS, Mnikhovich МV, Nagornaya DP, Pavlov PV, Kiryukhin AP, Fedorenko AA, et al. Gastric neuroendocrine tumors in patients with autoimmune gastritis. Clinical and Experimental Morphology. 2023; 12(3):19–27. (In Russ.). DOI: https://doi.org/10.31088/CEM2023.12.3.19-27.

57. Kazimirova AA, Kazachkov EL, Gorelik GL. Morphological characteristics of the neuroendocrine hyperplasia in chronic atrophic gastritis with autoimmune component. Ural Medical Journal. 2013;(3):15–18. (In Russ.). EDN: https://www.elibrary.ru/QAMFVZ.

58. Torbenson M, Abraham SC, Boitnott J, Yardley JH, Wu TT. Autoimmune gastritis: Distinct histological and immunohistochemical findings before complete loss of oxyntic glands. Modern Pathology. 2002; 15(2):102–109. DOI: https://doi.org/10.1038/modpathol.3880499.

59. Kulak O, Gurram B, Montgomery EA, Park JY. Pediatric autoimmune gastritis: Clinical correlates and histologic features. Human Pathology. 2021;116:31–38. DOI: https://doi.org/10.1016/j.humpath.2021.07.002.

60. Park JY, Cornish TC, Lam-Himlin D, Shi C, Montgomery E. Gastric lesions in patients with autoimmune metaplastic atrophic gastritis (AMAG) in a tertiary care setting. The American Journal of Surgical Pathology. 2010;34(11):1591–1598. DOI: https://doi.org/10.1097/PAS.0b013e3181f623af.

61. Li HL, Wang Y, Ren YB, Yang XS, Wang L, Zhang L, et al. Pyloric gland adenoma with low-grade intraepithelial neoplasia. Medicine. 2021;100(25): e26378. DOI: https://doi.org/10.1097/md.0000000000026378.

62. Vieth M, Montgomery EA. Some observations on pyloric gland adenoma: An uncommon and long ignored entity! Journal of Clinical Pathology. 2014;67(10):883–890. DOI: https://doi.org/10.1136/jclinpath-2014-202553.

63. Chen ZM, Scudiere JR, Abraham SC, Montgomery EA. Pyloric gland adenoma. The American Journal of Surgical Pathology. 2009;33(2):186–193. DOI: https://doi.org/10.1097/pas.0b013e31817d7ff4.

64. Hackeng WM, Montgomery EA, Giardiello FM, Singhi AD, Debeljak M, Eshleman JR, et al. Morphology and genetics of pyloric gland adenomas in familial adenomatous polyposis. Histopathology. 2016;70(4):549–557. DOI: https://doi.org/10.1111/his.13105.