J Pathol Transl Med.  2020 Mar;54(2):135-145. 10.4132/jptm.2019.11.06.

Colorectal epithelial neoplasm associated with gut-associated lymphoid tissue

Affiliations
  • 1Department of Pathology, Kosin University College of Medicine, Busan, Korea

Abstract

Background
Colorectal epithelial neoplasm extending into the submucosal gut-associated lymphoid tissue (GALT) can cause difficulties in the differential diagnosis. Regarding GALT-associated epithelial neoplasms, a few studies favor the term “GALT carcinoma” while other studies have mentioned the term “GALT-associated pseudoinvasion/epithelial misplacement (PEM)”.
Methods
The clinicopathologic characteristics of 11 cases of colorectal epithelial neoplasm associated with submucosal GALT diagnosed via endoscopic submucosal dissection were studied.
Results
Eight cases (72.7%) were in males. The median age was 59 years, and age ranged from 53 to 73. All cases had a submucosal tumor component more compatible with GALT-associated PEM. Eight cases (72.7%) were located in the right colon. Ten cases (90.9%) had a non-protruding endoscopic appearance. Nine cases (81.8%) showed continuity between the submucosal and surface adenomatous components. Nine cases showed (81.8%) focal defects or discontinuation of the muscularis mucosae adjacent to the submucosal GALT. No case showed hemosiderin deposits in the submucosa or desmoplastic reaction. No case showed single tumor cells or small clusters of tumor cells in the submucosal GALT. Seven cases (63.6%) showed goblet cells in the submucosa. No cases showed oncocytic columnar cells lining submucosal glands.
Conclusions
Our experience suggests that pathologists should be aware of the differential diagnosis of GALT-associated submucosal extension by colorectal adenomatous neoplasm. Further studies are needed to validate classification of GALT-associated epithelial neoplasms.

Keyword

Humans; Colorectal neoplasms; Lymphoid tissue; Adenomatous polyps

Figure

  • Fig. 1. Continuity of submucosal glands with surface adenomatous component and focal defect of muscularis mucosae adjacent to submucosal gut-associated lymphoid tissue (GALT). (A) Case 5. Tubular adenoma with high-grade dysplasia. Histologic continuity of submucosal glands with surface adenomatous component is seen. Submucosal glands with low-grade dysplasia show similar degree of differentiation compared with surface component. However, this neoplasm shows focal area of glands with complex architecture and corresponding high-grade cytologic features in surface mucosa elsewhere (depicted in inset). This case is more compatible with tubular adenoma with high-grade dysplasia than invasive adenocarcinoma, which usually shows less differentiated tumor cells in the deepest part of invasion. (B) Immunohistochemical (IHC) staining for desmin in case 5 shows focal defects of the muscularis mucosae with GALT-associated pseudoinvasion/epithelial misplacement (PEM). (C) Case 9. Tubular adenoma with high-grade dysplasia. Both surface adenomatous component and submucosal glands show high-grade dysplasia and histologic continuity across the muscularis mucosae. (D) IHC staining for desmin in case 9 highlights discontinuous muscularis mucosae. (E) Case 2. Tubular adenoma with high-grade dysplasia. In contrast to cases 5 and 9, no histologic continuity of submucosal glands with surface adenomatous component is seen. Inset depicts glands with high-grade dysplasia in surface mucosa. Narrow rim surrounding submucosal glands is not compatible with typical desmoplasia. Absence of single tumor cells/small clusters of tumor cells, poorly formed or back-to-back glands, solid tumor nests, or “true” desmoplasia favor diagnosis of tubular adenoma with high-grade dysplasia involving GALT (PEM) over adenocarcinoma with “true” submucosal invasion. (F) Intact muscularis mucosae with subjacent GALT of case 2 is identified with IHC staining for desmin. (G) Case 11. Tubular adenoma with low-grade dysplasia. Cystically dilated tumor glands cross through the muscularis mucosae. Note simultaneous crossing over by non-neoplastic glands (indicated by arrow). (H) IHC staining for desmin in case 11. PEM via GALT is accompanied by discontinuous muscularis mucosae rather than hypertrophy of muscularis mucosae.

  • Fig. 2. Case 3. (A) Histologic continuity along with subtle rimming of muscularis mucosae in submucosa (so-called herniation pattern) favor diagnosis of tubular adenoma with high-grade dysplasia over invasive adenocarcinoma. Depth of neoplasm is more than twice the thickness of surrounding normal colorectal mucosa. (B) Endoscopic appearance of case 3. Exact measurement of neoplasm depth is not available for endoscopist. Superficial neoplastic lesion with height more than one-third of diameter is compatible with the protruding type. (C) Immunohistochemical staining for desmin in case 3. Rimming of muscularis mucosa is indicated by red arrows. (D) Glands with high-grade dysplasia are seen under imaginary line connecting adjacent muscularis mucosa beneath normal mucosa. Panel D corresponds to green boxes of panels A and C. (E) Glands of surface mucosal layer with high-grade dysplasia.


Reference

1. Neutra MR, Mantis NJ, Kraehenbuhl JP. Collaboration of epithelial cells with organized mucosal lymphoid tissues. Nat Immunol. 2001; 2:1004–9.
Article
2. Rubio CA, Puppa G, de Petris G, Kis L, Schmidt PT. The third pathway of colorectal carcinogenesis. J Clin Pathol. 2018; 71:7–11.
Article
3. Elmore SA. Enhanced histopathology of mucosa-associated lymphoid tissue. Toxicol Pathol. 2006; 34:687–96.
Article
4. Langman JM, Rowland R. The number and distribution of lymphoid follicles in the human large intestine. J Anat. 1986; 149:189–94.
5. Kealy WF. Colonic lymphoid-glandular complex (microbursa): nature and morphology. J Clin Pathol. 1976; 29:241–4.
Article
6. Sipos F, Muzes G. Isolated lymphoid follicles in colon: switch points between inflammation and colorectal cancer? World J Gastroenterol. 2011; 17:1666–73.
Article
7. Nascimbeni R, Villanacci V, Mariani PP, et al. Aberrant crypt foci in the human colon: frequency and histologic patterns in patients with colorectal cancer or diverticular disease. Am J Surg Pathol. 1999; 23:1256–63.
8. Fu KI, Sano Y, Kato S, et al. Incidence and localization of lymphoid follicles in early colorectal neoplasms. World J Gastroenterol. 2005; 11:6863–6.
Article
9. Shah N, Thakkar B, Shen E, et al. Lymphocytic follicles and aggregates are a determinant of mucosal damage and duration of diarrhea. Arch Pathol Lab Med. 2013; 137:83–9.
Article
10. Rubio CA, Asmundsson J, Silva P, Illies C, Hartman J, Kis L. Lymphoid aggregates in Crohn’s colitis and mucosal immunity. Virchows Arch. 2013; 463:637–42.
Article
11. Shepherd NA, Griggs RK. Bowel cancer screening-generated diagnostic conundrum of the century: pseudoinvasion in sigmoid colonic polyps. Mod Pathol. 2015; 28 Suppl 1:S88–94.
Article
12. Lee HE, Wu TT, Chandan VS, Torbenson MS, Mounajjed T. Colonic adenomatous polyps involving submucosal lymphoglandular complexes: a diagnostic pitfall. Am J Surg Pathol. 2018; 42:1083–9.
13. McCarthy AJ, Chetty R. Gut-associated lymphoid tissue or socalled “dome” carcinoma of the colon: review. World J Gastrointest Oncol. 2019; 11:59–70.
Article
14. Rubio CA, De Petris G, Puppa G. Gut-associated lymphoid tissue (GALT) carcinoma in ulcerative colitis. Anticancer Res. 2018; 38:919–21.
Article
15. Zhou S, Ma Y, Chandrasoma P. Inverted lymphoglandular polyp in descending colon. Case Rep Pathol. 2015; 2015:646270.
Article
16. Kannuna H, Rubio CA, Silverio PC, et al. DOME/GALT type adenocarcimoma of the colon: a case report, literature review and a unified phenotypic categorization. Diagn Pathol. 2015; 10:92.
Article
17. Yamada M, Sekine S, Matsuda T. Dome-type carcinoma of the colon masquerading a submucosal tumor. Clin Gastroenterol Hepatol. 2013; 11:A30.
Article
18. Rubio CA, Befrits R, Ericsson J. Carcinoma in gut-associated lymphoid tissue in ulcerative colitis: Case report and review of literature. World J Gastrointest Endosc. 2013; 5:293–6.
Article
19. Yamada M, Sekine S, Matsuda T, et al. Dome-type carcinoma of the colon; a rare variant of adenocarcinoma resembling a submucosal tumor: a case report. BMC Gastroenterol. 2012; 12:21.
Article
20. Puppa G, Molaro M. Dome-type: a distinctive variant of colonic adenocarcinoma. Case Rep Pathol. 2012; 2012:284064.
Article
21. Coyne JD. Dome-type colorectal carcinoma: a case report and review of the literature. Colorectal Dis. 2012; 14:e360–2.
Article
22. Rubio CA, Lindh C, Björk J, Törnblom H, Befrits R. Protruding and non-protruding colon carcinomas originating in gut-associated lymphoid tissue. Anticancer Res. 2010; 30:3019–22.
23. Stewart CJ, Hillery S, Newman N, Platell C, Ryan G. Dome-type carcinoma of the colon. Histopathology. 2008; 53:231–4.
Article
24. Asmussen L, Pachler J, Holck S. Colorectal carcinoma with domelike phenotype: an under-recognised subset of colorectal carcinoma? J Clin Pathol. 2008; 61:482–6.
Article
25. Rubio CA, Talbot I. Lymphoid-associated neoplasia in herniated colonic mucosa. Histopathology. 2002; 40:577–9.
Article
26. Jass JR, Constable L, Sutherland R, et al. Adenocarcinoma of colon differentiating as dome epithelium of gut-associated lymphoid tissue. Histopathology. 2000; 36:116–20.
Article
27. Clouston AD, Clouston DR, Jass JR. Adenocarcinoma of colon differentiating as dome epithelium of gut-associated lymphoid tissue. Histopathology. 2000; 37:567.
Article
28. De Petris G, Lev R, Quirk DM, Ferbend PR, Butmarc JR, ElenitobaJohnson K. Lymphoepithelioma-like carcinoma of the colon in a patient with hereditary nonpolyposis colorectal cancer. Arch Pathol Lab Med. 1999; 123:720–4.
Article
29. Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin LH, Parkin MD. International Classification of Diseases for Oncology (ICD-O). 3rd ed. Geneva: World Health Organization;2013.
30. Stintzing S, Tejpar S, Gibbs P, Thiebach L, Lenz HJ. Understanding the role of primary tumour localisation in colorectal cancer treatment and outcomes. Eur J Cancer. 2017; 84:69–80.
Article
31. The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 2003; 58(6 Suppl):S3–43.
32. Vleugels JLA, Hazewinkel Y, Dekker E. Morphological classifications of gastrointestinal lesions. Best Pract Res Clin Gastroenterol. 2017; 31:359–67.
Article
33. Endoscopic Classification Review Group. Update on the paris classification of superficial neoplastic lesions in the digestive tract. Endoscopy. 2005; 37:570–8.
34. Kudo S, Lambert R, Allen JI, et al. Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointest Endosc. 2008; 68(4 Suppl):S3–47.
Article
35. Schlemper RJ, Hirata I, Dixon MF. The macroscopic classification of early neoplasia of the digestive tract. Endoscopy. 2002; 34:163–8.
Article
36. Lokuhetty D, White VA, Watanabe R, Cree IA; Organizacion Mundial de la Salud; International Agency for Research on Cancer. WHO classification of tumours. Vol. 1. Digestive system tumours. 5th ed. Lyon: IARC Press;2019.
37. Fenoglio-Preiser CM, Noffsinger AE, Stemmermann GN, Lantz PE, Isaacson PG. Gastrointestinal pathology: an atlas and text. 3rd ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins;2008. p. 926–31.
38. Muto T, Bussey HJ, Morson BC. Pseudo-carcinomatous invasion in adenomatous polyps of the colon and rectum. J Clin Pathol. 1973; 26:25–31.
Article
39. Dirschmid K, Kiesler J, Mathis G, Beller S, Stoss F, Schobel B. Epithelial misplacement after biopsy of colorectal adenomas. Am J Surg Pathol. 1993; 17:1262–5.
Article
40. Yantiss RK, Bosenberg MW, Antonioli DA, Odze RD. Utility of MMP-1, p53, E-cadherin, and collagen IV immunohistochemical stains in the differential diagnosis of adenomas with misplaced epithelium versus adenomas with invasive adenocarcinoma. Am J Surg Pathol. 2002; 26:206–15.
Article
41. Tanizawa T, Seki T, Nakano M, Kamiyama R. Pseudoinvasion of the colorectal polypoid tumors: serial section study of problematic cases. Pathol Int. 2003; 53:584–90.
Article
42. Molavi D, Argani P. Distinguishing benign dissecting mucin (stromal mucin pools) from invasive mucinous carcinoma. Adv Anat Pathol. 2008; 15:1–17.
Article
43. Loughrey MB, Shepherd NA. The pathology of bowel cancer screening. Histopathology. 2015; 66:66–77.
Article
44. Panarelli NC, Somarathna T, Samowitz WS, et al. Diagnostic challenges caused by endoscopic biopsy of colonic polyps: a systematic evaluation of epithelial misplacement with review of problematic polyps from the bowel cancer screening program, United Kingdom. Am J Surg Pathol. 2016; 40:1075–83.
45. Ferreira da Silva MJ, Pinho R, Wen X, Tente D, Leite S, Carvalho J. Adenoma with pseudoinvasion: s crucial differential diagnosis for invasive adenocarcinoma. Gastroenterol Hepatol. 2017; 40:96–8.
46. Chang HJ, Park CK, Kim WH, et al. A standardized pathology report for colorectal cancer. Korean J Pathol. 2006; 40:193–203.
47. Rubio CA. Ectopic colonic mucosa in ulcerative colitis and in Crohn’s disease of the colon. Dis Colon Rectum. 1984; 27:182–6.
Article
48. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013; 310:2191–4.
49. Nauss KM, Locniskar M, Pavlina T, Newberne PM. Morphology and distribution of 1,2-dimethylhydrazine dihydrochloride-induced colon tumors and their relationship to gut-associated lymphoid tissue in the rat. J Natl Cancer Inst. 1984; 73:915–24.
50. Carter JW, Lancaster HK, Hardman WE, Cameron IL. Distribution of intestine-associated lymphoid tissue, aberrant crypt foci, and tumors in the large bowel of 1,2-dimethylhydrazine-treated mice. Cancer Res. 1994; 54:4304–7.
51. Hardman WE, Cameron IL. Colonic crypts located over lymphoid nodules of 1,2-dimethylhydrazine-treated rats are hyperplastic and at high risk of forming adenocarcinomas. Carcinogenesis. 1994; 15:2353–61.
Article
52. Rubio CA, Shetye J, Jaramillo E. Non-polypoid adenomas of the colon are associated with subjacent lymphoid nodules: an experimental study in rats. Scand J Gastroenterol. 1999; 34:504–8.
53. Rubio CA. The histogenesis of the third pathway of colonic carcinogenesis in rats. Anticancer Res. 2017; 37:1039–42.
54. Dukes C, Bussey HJ. The number of lymphoid follicles of the human large intestine. J Pathol Bacteriol. 1926; 29:111–6.
Article
55. O’Leary AD, Sweeney EC. Lymphoglandular complexes of the colon: structure and distribution. Histopathology. 1986; 10:267–83.
Article
56. Rubio CA, Schmidt PT. Gut-associated lymphoid tissue (GALT) carcinoma or dome carcinoma? Anticancer Res. 2016; 36:5385–7.
Article
57. Greene FL. Epithelial misplacement in adenomatous polyps of the colon and rectum. Cancer. 1974; 33:206–17.
Article
58. Fenoglio-Preiser CM, Lantz P, Listrom M, Noffsinger A, Riker F, Stemmermann G. Gastrointestinal pathology: an atlas and text. 2nd ed. Philadelphia: Lippincott-Raven;1999.
59. Schlemper RJ, Itabashi M, Kato Y, et al. Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma. Cancer. 1998; 82:60–9.
Article
60. Risio M. The natural history of pT1 colorectal cancer. Front Oncol. 2012; 2:22.
Article
61. Quirke P, Risio M, Lambert R, von Karsa L, Vieth M. Quality assurance in pathology in colorectal cancer screening and diagnosis-European recommendations. Virchows Arch. 2011; 458:1–19.
Article
62. Lewin MR, Fenton H, Burkart AL, Sheridan T, Abu-Alfa AK, Montgomery EA. Poorly differentiated colorectal carcinoma with invasion restricted to lamina propria (intramucosal carcinoma): a follow-up study of 15 cases. Am J Surg Pathol. 2007; 31:1882–6.
Article
63. Kenney BC, Jain D. Identification of lymphatics within the colonic lamina propria in inflammation and neoplasia using the monoclonal antibody D2-40. Yale J Biol Med. 2008; 81:103–13.
64. Fenoglio CM, Kaye GI, Lane N. Distribution of human colonic lymphatics in normal, hyperplastic, and adenomatous tissue. Its relationship to metastasis from small carcinomas in pedunculated adenomas, with two case reports. Gastroenterology. 1973; 64:51–66.
65. Hashimoto H, Horiuchi H, Kurata A, et al. Intramucosal colorectal carcinoma with lymphovascular invasion: clinicopathological characteristics of nine cases. Histopathology. 2019; 74:1055–66.
Article
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