Document Type : Review Article

Authors

Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

The ileum undergoes endoscopic biopsy much more than before. Most of these biopsies are either completely normal or show non-specific changes. Nevertheless, in some diseases, ileal biopsy is diagnostic, and in some cases it may be the only anatomical location of the disease. Endoscopically normal mucosal biopsy is unlikely to provide useful diagnostic information and is not routinely recommended. However, in the presence of ileitis, ulcers, or erosions, biopsies can be very helpful. Ileitis might be induced by various conditions including infectious diseases, vasculitis, medication-induced, ischemia, eosinophilic enteritis, tumors etc. The conclusive cause of the condition is proposed by a comprehensive clinical background and physical examination, laboratory investigations, ileocolonoscopy, and imaging findings. Ileoscopy and biopsy are mainly useful in correctly selected cases such as patients that present with inflammatory diarrhea and endoscopic lesions. This review is meant to provide a simple algorithmic approach to the ileal biopsy samples. There are several boxes that give diagnostic clues and an idea behind the categories of ileal disorders.
This review is based on the reviewed literature and the authors' experiences. We have summarized different histological patterns in the ileal biopsy specimens that can be used in the diagnosis of inflammatory disorders of the ileum.
This review provides an algorithmic approach to the clinicopathological features of inflammatory disorders of the ileum with a brief discussion of some important related issues.

Keywords

Main Subjects

  1. Bidarizerehpoosh F, Ghasemi S, Moradi A, Moradi A, Kazeminezhad B, Jamali E, et al. Multicentric Study of Clinicopathological Features of Primary Gastrointestinal Lymphoma of Iran: from 2011-2016. Int J Cancer Manag. 2021;14(6). [DOI:10.5812/ijcm.97892]
  2. Jouret-Mourin A, Faa G, Geboes K. Colitis: A Practical Approach to Colon and Ileum Biopsy Interpretation: Springer; 2018. [DOI:10.1007/978-3-319-89503-1]
  3. Koksal AR, Boga S, Alkim H, Ergun M, Bayram M, Sakiz D, et al. How does a biopsy of endoscopically normal terminal ileum contribute to the diagnosis? Which patients should undergo biopsy? Libyan J Med. 2014;9(1). [DOI:10.3402/ljm.v9.23441] [PMCID]
  4. Magro F, Langner C, Driessen A, Ensari A, Geboes K, Mantzaris G, et al. European consensus on the histopathology of inflammatory bowel disease. J Crohn's Colitis. 2013;7(10):827-51. [DOI:10.1016/j.crohns.2013.06.001] [PMID]
  5. Mojtahed A, Pai RK, Anderson MW, Arber DA, Longacre TA. Reactive lymphoid hyperplasia of the terminal ileum: a benign (lymphoma-like) condition that may harbor aberrant immunohistochemical patterns or clonal immunoglobulin heavy chain gene rearrangements. Appl Immunohistochem Molecul Morphol. 2014;22(8):585-92. [PMID] [DOI:10.1097/01.pai.0000446497.93867.98]
  6. Gersemann M, Stange EF, Wehkamp J. From intestinal stem cells to inflammatory bowel diseases. World J Gastroenterol: WJG. 2011;17 (27):3198.
  7. Pang L-C. Intussusception revisited: clinicopathologic analysis of 261 cases, with emphasis on pathogenesis. Southern Med J. 1989;82(2):215-28. [DOI:10.1097/00007611-198902000-00017]
  8. Van Kruiningen HJ, West AB, Freda BJ, Holmes KA. Distribution of Peyer's patches in the distal ileum. Inflamm Bowel Dis. 2002;8(3):180-5. [DOI:10.1097/00054725-200205000-00004] [PMID]
  9. Shepherd NA, Crocker PR, Smith AP, Levison DA. Exogenous pigment in Peyer's patches. Hum Pathol. 1987;18(1):50-4. [DOI:10.1016/S0046-8177(87)80193-4]
  10. Eidelman S, Lagunoff D. The morphology of the normal human rectal biopsy. Hum Pathol. 1972;3(3):389-401. [DOI:10.1016/S0046-8177(72)80039-X]
  11. Bejarano PA, Aranda-Michel J, Fenoglio-Preiser C. Histochemical and immunohistochemical characterization of foamy histiocytes (muciphages and xanthelasma) of the rectum. Am J Surg Pathol. 2000;24(7):1009-15. [PMID] [DOI:10.1097/00000478-200007000-00013]
  12. Seldenrijk C, Morson B, Meuwissen S, Schipper N, Lindeman J, Meijer C. Histopathological evaluation of colonic mucosal biopsy specimens in chronic inflammatory bowel disease: diagnostic implications. Gut. 1991;32(12):1514-20. [DOI:10.1136/gut.32.12.1514] [PMID] [PMCID]
  13. Cuvelier C, Demetter P, Mielants H, Veys E, De Vos M. Interpretation of ileal biopsies: morphological features in normal and diseased mucosa. Histopathology. 2001;38(1):1-12. [DOI:10.1046/j.1365-2559.2001.01070.x] [PMID]
  14. Goldstein JL, Eisen GM, Lewis B, Gralnek IM, Zlotnick S, Fort JG. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol. 2005;3(2): 133-41. [DOI:10.1016/S1542-3565(04)00619-6]
  15. Heresbach D, Alexandre J, Branger B, Bretagne J, Cruchant E, Dabadie A, et al. Frequency and significance of granulomas in a cohort of incident cases of Crohn's disease. Gut. 2005;54(2):215-22. [DOI:10.1136/gut.2004.041715] [PMID] [PMCID]
  16. Das P, Gahlot G, Mehta R, Gupta S. Interpretation of ileal biopsies. Indian J Pathol Microbiol. 2015; 58(2):146-. [DOI:10.4103/0377-4929.155302] [PMID]
  17. Tse CS, Deepak P, Smyrk TC, Raffals LE. Isolated acute terminal ileitis without preexisting inflammatory bowel disease rarely progresses to Crohn's disease. Dig Dis Sci. 2017;62(12):3557-62. [DOI:10.1007/s10620-017-4803-8] [PMID]
  18. Gleason TH, Patterson SD. The pathology of Yersinia enterocolitica ileocolitis. Am J Surg Pathol. 1982;6(4):347-55. [DOI:10.1097/00000478-198206000-00007] [PMID]
  19. Naktin J, Beavis KG. Yersinia Enterocolitica and Yersinia Pseudotuherculosis. Clin Lab Med. 1999;19(3):523-36. [DOI:10.1016/S0272-2712(18)30102-1]
  20. Vantrappen G, Ponette E, Geboes K, Bertrand P. Yersinia enteritis and enterocolitis: gastroenterological aspects. Gastroenterology. 1977;72(2):220-7. [DOI:10.1016/S0016-5085(77)80076-0]
  21. Zippi M, Colaiacomo MC, Marcheggiano A, Pica R, Paoluzi P, Iaiani G, et al. Mesenteric adenitis caused by Yersinia pseudotubercolosis in a patient subsequently diagnosed with Crohn's disease of the terminal ileum. World J Gastroenterol. 2006;12(24):3933. [PMID] [PMCID] [DOI:10.3748/wjg.v12.i24.3933]
  22. Aabakken L. Small-bowel side-effects of non-steroidal anti-inflammatory drugs. Eur J Gastroenterol Hepatol. 1999;11(4):383-8. [DOI:10.1097/00042737-199904000-00004] [PMID]
  23. Koulaouzidis A, Douglas S, Plevris JN. Blue mode does not offer any benefit over white light when calculating Lewis score in small-bowel capsule endoscopy. World J Gastrointest Endosc. 2012;4(2):33. [DOI:10.4253/wjge.v4.i2.33] [PMID] [PMCID]
  24. Théophile H, David X-R, Miremont-Salamé G, Haramburu F. Five cases of sprue-like enteropathy in patients treated by olmesartan. Dig Liver Dis. 2014;46(5):465-9. [DOI:10.1016/j.dld.2013.12.014] [PMID]
  25. Geboes K, Jouret-Mourin A. Ileitis. Colitis: Springer; 2018. p. 231-42. [DOI:10.1007/978-3-319-89503-1_17]
  26. Wright NA, Pike C, Elia G. Induction of a novel epidermal growth factor-secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells. Nature. 1990;343(6253):82-5. [DOI:10.1038/343082a0] [PMID]
  27. Abdelrazeq AS, Wilson TR, Leitch DL, Lund JN, Leveson SH. Ileitis in ulcerative colitis: is it a backwash? Dis Colon Rectum. 2005;48(11): 2038-46. [DOI:10.1007/s10350-005-0160-3] [PMID]
  28. Goldstein NS. Isolated ileal erosions in patients with mildly altered bowel habits: A follow-up study of 28 patients. Am J Clin Pathol. 2006;125(6):838-46. [DOI:10.1309/4PK0G68M2G1L6X47] [PMID]
  29. Haskell H, Andrews Jr CW, Reddy SI, Dendrinos K, Farraye FA, Stucchi AF, et al. Pathologic features and clinical significance of "backwash" ileitis in ulcerative colitis. Am J Surg Pathol. 2005;29(11):1472-81. [PMID] [DOI:10.1097/01.pas.0000176435.19197.88]
  30. Kobayashi M, Ito M, Nakagawa A, Matsushita M, Nishikimi N, Sakurai T, et al. Neutrophil and endothelial cell activation in the vasa vasorum in vasculo-Behcet disease. Histopathology. 2000;36(4):362-71. [DOI:10.1046/j.1365-2559.2000.00859.x] [PMID]
  31. Nikzamir M, Nejad MR, Sadeghi A, Moradi A, Mohaghegh H, Asadzadeh-Aghdaei H, et al. The correlation between endoscopy manifestations and pathology outcome for diagnosis of celiac disease. Int J Celiac Dis. 2017;5(3):101-3.
  32. Sadeghi A, Rad N, Ashtari S, Rostami-Nejad M, Moradi A, Haghbin M, et al. The value of a biopsy in celiac disease follows up: assessment of the small bowel after 6 and 24 months treatment with a gluten free diet. Rev Esp Enferm Dig. 2020;112(2):101-8. [DOI:10.17235/reed.2019.5947/2018] [PMID]
  33. Arnold C, Lam-Himlin D, Montgomery EA. Atlas of Gastrointestinal Pathology: A Pattern Based Approach to Neoplastic Biopsies: Lippincott Williams & Wilkins; 2018.
  34. Desnues B, Al Moussawi K, Fenollar F. New insights into Whipple's disease and Tropheryma whipplei infections. Microbes Infect. 2010;12 (14-15):1102-10. [DOI:10.1016/j.micinf.2010.08.001] [PMID]
  35. Sid'Amar S, Puppa G. Whipple's disease affecting ileal peyer's patches: the first case report. Case Rep Pathol. 2019;2019. [DOI:10.1155/2019/1509745] [PMID] [PMCID]
  36. Ranchod M, Lewin KJ, Dorfman RF. Lymphoid hyperplasia of the gastrointestinal tract. A study of 26 cases and review of the literature. Am J Surg Pathol. 1978;2(4):383-400. [PMID] [DOI:10.1097/00000478-197812000-00005]
  37. Jonsson OT, Birgisson S, Reykdal S. Resolution of nodular lymphoid hyperplasia of the gastrointestinal tract following chemotherapy for extraintestinal lymphoma. Dig Dis Sci. 2002;47 (11):2463-5. [DOI:10.1023/A:1020547723325] [PMID]
  38. Lin R, Lu H, Zhou G, Wei Q, Liu Z. Clinicopathological and Ileocolonoscopic Characteristics in Patients with Nodular Lymphoid Hyperplasia in the Terminal Ileum. Int J Med Sci. 2017;14(8):750. [DOI:10.7150/ijms.19480] [PMID] [PMCID]
  39. Collins MH. Histopathologic features of eosinophilic esophagitis and eosinophilic gastrointestinal diseases. Gastroenterol Clin. 2014;43(2):257-68. [DOI:10.1016/j.gtc.2014.02.007] [PMID]
  40. Hentschel F, Jansen AF, Günther M, Pauli R, Lüth S. Eosinophil counts in mucosal biopsies of the ileum and colon: interobserver variance affects diagnostic accuracy. Pathology Res Int. 2018;2018. [DOI:10.1155/2018/2638258] [PMID] [PMCID]
  41. Kaushal R, Quon MG. Eosinophilic Colitis. Proceedings of UCLA Health. 2019;23.
  42. Yantiss RK. Eosinophils in the GI tract: how many is too many and what do they mean? Mod Pathol. 2015;28(1):S7-S21. [DOI:10.1038/modpathol.2014.132] [PMID]
  43. Marston A, Clarke J, Garcia JG, Miller A. Intestinal function and intestinal blood supply: a 20 year surgical study. Gut. 1985;26(7):656-66. [DOI:10.1136/gut.26.7.656] [PMID] [PMCID]
  44. Ottinger LW. Mesenteric ischemia. N Engl J Med. 1982;307(9):535-7. [DOI:10.1056/NEJM198208263070905] [PMID]
  45. Umphrey H CC, Lockhart ME. Differential diagnosis of small
  46. bowel ischemia. Radiol Clin North Am. 2008;46:943-52. [DOI:10.1016/j.rcl.2008.06.004] [PMID]
  47. Greenson JK, Lauwers GY, Montgomery EA, Owens SR, Polydorides AD, Srivastava A. Diagn Pathol. 2018.
  48. Segmental Xanthomatosis of the Ileum. ELECTRONIC IMAGE OF THE MONTH. 2019;17(3). [DOI:10.1016/j.cgh.2018.01.013] [PMID]
  49. Sauntry J, Knudtson K. A technique for marking the mucosa of the gastrointestinal tract after polypectomy. Cancer. 1958;11(3):607-10. [DOI:10.1002/1097-0142(195805/06)11:33.0.CO;2-Y]
  50. Trakarnsanga A, Akaraviputh T. Endoscopic tattooing of colorectal lesions: is it a risk-free procedure? World J Gastrointest Endosc. 2011;3(12):256. [DOI:10.4253/wjge.v3.i12.256] [PMID] [PMCID]
  51. Bisordi WM, Kleinman MS. Melanosis duodeni. Gastrointest Endosc. 1976;23(1):37-8. [DOI:10.1016/S0016-5107(76)73576-4]
  52. Cantu JA, Adler DG. Pseudomelanosis duodeni. Endoscopy. 2005;37(08):789-. [DOI:10.1055/s-2005-870144] [PMID]
  53. Fernando SS. Pseudomelanosis duodeni: a case report with electron-probe X-ray analysis. Pathology. 1990;22(3):169-72. [DOI:10.3109/00313029009063559] [PMID]
  54. Giusto D, Jakate S. Pseudomelanosis duodeni: associated with multiple clinical conditions and unpredictable iron sustainability-a case series. Endoscopy. 2008;40(02):165-7. [DOI:10.1055/s-2007-995472] [PMID]
  55. Rex DK, Jersild Jr RA. Further characterization of the pigment in pseudomelanosis duodeni in three patients. Gastroenterology. 1988;95(1):177-82. [DOI:10.1016/0016-5085(88)90308-3]
  56. de Magalhães Costa MH, Pegado MdGF, Vargas C, Castro MEC, Madi K, Nunes T, et al. Pseudomelanosis duodeni associated with chronic renal failure. World J Gastroenterol: WJG. 2012;18(12):1414. [PMID] [PMCID] [DOI:10.3748/wjg.v18.i12.1414]
  57. Holmes EJ. Remarks on further properties of formalin pigment. Arch Dermatol. 1971;103 (5): 565-6. [DOI:10.1001/archderm.1971.04000170099028] [PMID]