Abstract
Certain types of colitides, such as collagenous colitis, lymphocytic colitis, and ischemic colitis, have distinct histologic features that allow for a specific diagnosis. However, in most colonic biopsy specimens, a definite diagnosis cannot be established on the basis of histology alone. Thus, in most cases of colitis, it is helpful to utilize a systematic approach in order to recognize patterns of injury. This information in conjunction with clinical and laboratory findings may help pathologists narrow the differential diagnosis and/or establish a more definite etiology for the patient’s illness in order to guide clinical management. We provide general guidelines to distinguish variations in normal mucosa and biopsy procedure-related artifacts from true inflammatory conditions. Inflammatory conditions may be further categorized into those with predominantly lymphoplasmacytic inflammation (with or without neutrophils), predominantly neutrophilic inflammation, predominantly eosinophilic inflammation, or paucicellular colitis, since each of these patterns of inflammation are associated with a distinct differential diagnosis. This review will focus on a pattern-based algorithmic approach to evaluating biopsies of patients who present to physicians with signs and symptoms of colitis.
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References
Pascal RR, Gramlich TL, Parker KM, Gansler TS (1997) Geographic variations in eosinophil concentration in normal colonic mucosa. Mod Pathol 10(4):363–365
Ayata G, Ithamukkala S, Sapp H, Shaz BH, Brien TP, Wang HH, Antonioli DA, Farraye FA, Odze RD (2002) Prevalence and significance of inflammatory bowel disease-like morphologic features in collagenous and lymphocytic colitis. Am J Surg Pathol 26(11):1414–1423. https://doi.org/10.1097/00000478-200211000-00003
Arnold CA, Limketkai BN, Illei PB, Montgomery E, Voltaggio L (2013) Syphilitic and lymphogranuloma venereum (LGV) proctocolitis: clues to a frequently missed diagnosis. Am J Surg Pathol 37(1):38–46. https://doi.org/10.1097/PAS.0b013e31826a523e
Selbst MK, Ahrens WA, Robert ME, Friedman A, Proctor DD, Jain D (2009) Spectrum of histologic changes in colonic biopsies in patients treated with mycophenolate mofetil. Mod Pathol 22(6):737–743. https://doi.org/10.1038/modpathol.2009.44
Dubeau M-F, Iacucci M, Beck PL, Moran GW, Kaplan GG, Ghosh S, Panaccione R (2013) Drug-induced inflammatory bowel disease and IBD-like conditions. Inflamm Bowel Dis 19(2):445–456. https://doi.org/10.1002/ibd.22990
Riley SA, Mani V, Goodman MJ, Dutt S, Herd ME (1991) Microscopic activity in ulcerative colitis: what does it mean? Gut 32(2):174–178. https://doi.org/10.1136/gut.32.2.174
Odze R, Antonioli D, Peppercorn M, Goldman H (1993) Effect of topical 5-aminosalicylic acid (5-ASA) therapy on rectal mucosal biopsy morphology in chronic ulcerative colitis. Am J Surg Pathol 17(9):869–875. https://doi.org/10.1097/00000478-199309000-00002
Kleer CG, Appelman HD (1998) Ulcerative colitis: patterns of involvement in colorectal biopsies and changes with time. Am J Surg Pathol 22(8):983–989. https://doi.org/10.1097/00000478-199808000-00008
Bernstein CN, Shanahan F, Anton PA, Weinstein WM (1995) Patchiness of mucosal inflammation in treated ulcerative colitis: a prospective study. Gastrointest Endosc 42(3):232–237. https://doi.org/10.1016/S0016-5107(95)70097-8
Kim B, Barnett JL, Kleer CG, Appelman HD (1999) Endoscopic and histological patchiness in treated ulcerative colitis. Am J Gastroenterol 94(11):3258–3262. https://doi.org/10.1111/j.1572-0241.1999.01533.x
Markowitz J, Kahn E, Grancher K, Hyams J, Treem W, Daum F (1993) Atypical rectosigmoid histology in children with newly diagnosed ulcerative colitis. Am J Gastroenterol 88(12):2034–2037
Glickman JN, Bousvaros A, Farraye FA, Zholudev A, Friedman S, Wang HH, Leichtner AM, Odze RD (2004) Pediatric patients with untreated ulcerative colitis may present initially with unusual morphologic findings. Am J Surg Pathol 28(2):190–197. https://doi.org/10.1097/00000478-200402000-00006
Washington K, Greenson JK, Montgomery E, Shyr Y, Crissinger KD, Polk DB, Barnard J, Lauwers GY (2002) Histopathology of ulcerative colitis in initial rectal biopsy in children. Am J Surg Pathol 26(11):1441–1449. https://doi.org/10.1097/00000478-200211000-00006
D’Haens G, Geboes K, Peeters M et al (1997) Patchy cecal inflammation associated with distal ulcerative colitis: a prospective endoscopic study. Am J Gastroenterol 92(8):1275–1279
Okawa K, Aoki T, Sano K, Harihara S, Kitano A, Kuroki T (1998) Ulcerative colitis with skip lesions at the mouth of the appendix: a clinical study. Am J Gastroenterol 93(12):2405–2410. https://doi.org/10.1111/j.1572-0241.1998.00695.x
Yang SK, Jung HY, Kang GH, Kim YM, Myung SJ, Shim KN, Hong WS, Min YI (1999) Appendiceal orifice inflammation as a skip lesion in ulcerative colitis: an analysis in relation to medical therapy and disease extent. Gastrointest Endosc 49(6):743–747. https://doi.org/10.1016/S0016-5107(99)70293-2
Davison AM, Dixon MF (1990) The appendix as a “skip lesion” in ulcerative colitis. Histopathology 16(1):93–95. https://doi.org/10.1111/j.1365-2559.1990.tb01069.x
Groisman GM, George J, Harpaz N (1994) Ulcerative appendicitis in universal and nonuniversal ulcerative colitis. Mod Pathol 7(3):322–325
Geboes K, Ectors N, D’Haens G, Rutgeerts P (1998) Is ileoscopy with biopsy worthwhile in patients presenting with symptoms of inflammatory bowel disease? Am J Gastroenterol 93(2):201–206. https://doi.org/10.1111/j.1572-0241.1998.00201.x
Dilauro S, Crum-Cianflone NF (2010) Ileitis: when it is not Crohn’s disease. Curr Gastroenterol Rep 12(4):249–258. https://doi.org/10.1007/s11894-010-0112-5
Lengeling RW, Mitros FA, Brennan JA, Schulze KS (2003) Ulcerative ileitis encountered at ileo-colonoscopy: likely role of nonsteroidal agents. Clin Gastroenterol Hepatol 1(3):160–169. https://doi.org/10.1016/S1542-3565(03)70031-7
Quigley EMM (2014) Small intestinal bacterial overgrowth: what it is and what it is not. Curr Opin Gastroenterol 30(2):141–146. https://doi.org/10.1097/MOG.0000000000000040
Hamilton MJ, Makrauer FM, Golden K, Wang H, Friedman S, Burakoff RB, Levine JS, Joshi P, Banks PA, Odze RD (2016) Prospective evaluation of terminal ileitis in a surveillance population of patients with ulcerative colitis. Inflamm Bowel Dis 22(10):2448–2455. https://doi.org/10.1097/MIB.0000000000000911
McCready FJ, Bargen JA (1949) Involvement of the ileum in chronic ulcerative colitis. N Engl J Med 240(4):119–127. https://doi.org/10.1056/NEJM194901272400401
Saltzstein SL, Rosenberg BF (1963) Ulcerative colitis of the ileum, and regional enteritis of the colon. A comparative histopathology study. Am J Clin Pathol 40(6):610–623. https://doi.org/10.1093/ajcp/40.6.610
Haskell H, Andrews CW, Reddy SI et al (2005) Pathologic features and clinical significance of “backwash” ileitis in ulcerative colitis. Am J Surg Pathol 29(11):1472–1481. https://doi.org/10.1097/01.pas.0000176435.19197.88
Patil DT, Odze RD (2017) Backwash is hogwash: the clinical significance of ileitis in ulcerative colitis. Am J Gastroenterol 112(8):1211–1214. https://doi.org/10.1038/ajg.2017.182
Yao K, Yao T, Iwashita A, Matsui T, Kamachi S (2000) Microaggregate of immunostained macrophages in noninflamed gastroduodenal mucosa: a new useful histological marker for differentiating Crohn’s colitis from ulcerative colitis. Am J Gastroenterol 95(8):1967–1973. https://doi.org/10.1111/j.1572-0241.2000.02258.x
Lin J, McKenna BJ, Appelman HD (2010) Morphologic findings in upper gastrointestinal biopsies of patients with ulcerative colitis: a controlled study. Am J Surg Pathol 34(11):1672–1677. https://doi.org/10.1097/PAS.0b013e3181f3de93
Ikeuchi H, Hori K, Nishigami T, Nakano H, Uchino M, Nakamura M, Kaibe N, Noda M, Yanagi H, Yamamura T (2006) Diffuse gastroduodenitis and pouchitis associated with ulcerative colitis. World J Gastroenterol 12(36):5913–5915. https://doi.org/10.3748/wjg.v12.i36.5913
Valdez R, Appelman HD, Bronner MP, Greenson JK (2000) Diffuse duodenitis associated with ulcerative colitis. Am J Surg Pathol 24(10):1407–1413. https://doi.org/10.1097/00000478-200010000-00011
Tobin JM, Sinha B, Ramani P, Saleh ARH, Murphy MS (2001) Upper gastrointestinal mucosal disease in pediatric Crohn disease and ulcerative colitis: a blinded, controlled study. J Pediatr Gastroenterol Nutr 32(4):443–448. https://doi.org/10.1097/00005176-200104000-00010
Yantiss RK, Sapp HL, Farraye FA, El-Zammar O, O’Brien MJ, Fruin AB, Stucchi AF, Brien TP, Becker JM, Odze RD (2004) Histologic predictors of pouchitis in patients with chronic ulcerative colitis. Am J Surg Pathol 28(8):999–1006. https://doi.org/10.1097/01.pas.0000126758.35603.8d
Mahadeva U, Martin JP, Patel NK, Price AB (2002) Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn’s disease from ulcerative colitis. Histopathology 41(1):50–55. https://doi.org/10.1046/j.1365-2559.2002.01416.x
Heppell J, Farkouh E, Dubé S, Péloquin A, Morgan S, Bernard D (1986) Toxic megacolon. An analysis of 70 cases. Dis Colon Rectum 29(12):789–792. https://doi.org/10.1007/BF02555345
Yantiss RK, Farraye FA, O’Brien MJ et al (2006) Prognostic significance of superficial fissuring ulceration in patients with severe “indeterminate” colitis. Am J Surg Pathol 30(2):165–170. https://doi.org/10.1097/01.pas.0000189178.00440.bf
Lynch JP, Fishbein M, Echavarria M (2011) Adenovirus. Semin Respir Crit Care Med 32(04):494–511. https://doi.org/10.1055/s-0031-1283287
García Rodríguez LA, Ruigómez A, Panés J (2006) Acute gastroenteritis is followed by an increased risk of inflammatory bowel disease. Gastroenterology 130(6):1588–1594. https://doi.org/10.1053/j.gastro.2006.02.004
Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH (1970) Eosinophilic gastroenteritis. Medicine (Baltimore) 49(4):299–319. https://doi.org/10.1097/00005792-197007000-00003
Doyle LA, Sepehr GJ, Hamilton MJ, Akin C, Castells MC, Hornick JL (2014) A clinicopathologic study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of mucosal mast cell density in irritable bowel syndrome and asymptomatic patients. Am J Surg Pathol 38(6):832–843. https://doi.org/10.1097/PAS.0000000000000190
Horny HP, Metcalfe DD, Bennett JM, et al. (2008) Mastocytosis. In: WHO classification of tumors of hematopoietic and lymphoid tissues, Swerdlow SH, campo E, Harris NL, et al, 4th edition. International Agency for Research and Cancer (IARC); Lyon (France), pp 54–63
Star KV, Ho VT, Wang HH, Odze RD (2013) Histologic features in colon biopsies can discriminate mycophenolate from GVHD-induced colitis. Am J Surg Pathol 37(9):1319–1328. https://doi.org/10.1097/PAS.0b013e31829ab1ef
Vieth M, Montgomery E (2017) Medication-associated gastrointestinal tract injury. Virchows Arch 470(3):245–266. https://doi.org/10.1007/s00428-017-2077-3
Marginean EC (2016) The ever-changing landscape of drug-induced injury of the lower gastrointestinal tract. Arch Pathol Lab Med 140(8):748–758. https://doi.org/10.5858/arpa.2015-0451-RA
De Petris G, De Marco L, López JI (2017) Drug-induced gastrointestinal injury (DIGI). Updates, reflections and key points. Pathologica 109(2):97–109
McCarthy AJ, Lauwers GY, Sheahan K (2015) Iatrogenic pathology of the intestines. Histopathology 66(1):15–28. https://doi.org/10.1111/his.12598
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Patil, D.T., Odze, R.D. Biopsy diagnosis of colitis: an algorithmic approach. Virchows Arch 472, 67–80 (2018). https://doi.org/10.1007/s00428-017-2274-0
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DOI: https://doi.org/10.1007/s00428-017-2274-0