Demarcated redness associated with increased vascular density/size: a useful marker of flat-type dysplasia in patients with ulcerative colitis

Abstract

Background and study aims Recent advances in endoscopic equipment and diagnostic techniques have improved the detection of dysplasia in the inflamed mucosa of patients with ulcerative colitis (UC). However, it remains difficult to endoscopically identify flat-type dysplasia which has been formerly recognized as invisible dysplasia.

Patients and methods In this retrospective, single-center study, we endoscopically identified 10 cases of flat-type-predominant dysplasia by targeted biopsy among 38 intramucosal dysplasia lesions from patients with UC who underwent surgical or endoscopic resection from 2007 to 2017. Their endoscopic and histological features were examined, including color changes, intramucosal vascular density/size, and vascular endothelial growth factor (VEGF) expression.

Results All flat-type-predominant dysplasias were endoscopically recognized as demarcated red-colored areas and histologically diagnosed as low- (LGDs) or high-grade dysplasias (HGDs). Immunohistochemical examination using resected specimens revealed that flat-type dysplasia was characterized by significantly increased CD34-positive vascular density (LGDs, 1.7-fold, P < 0.01; HGDs, 2.2-fold, P < 0.01) and size (LGDs, 1.03-fold, P < 0.01; HGDs, 1.11-fold, P < 0.01) in the mucosa, compared to adjacent non-neoplastic areas. Increased numbers of vessels were observed at the base of the mucosa in LGDs, whereas HGDs contained increased/enlarged vessels throughout the mucosa. Moreover, VEGF expression was elevated in all dysplastic epithelia.

Conclusions Demarcated red-colored areas, histologically characterized by an increased vascular density/size in the mucosa, are an endoscopic sign of formerly invisible flat-type dysplasia in patients with UC and should be considered for targeted biopsy. Prospective studies focusing on the mucosal color change for their early detection would be desirable in the future.

Publication History

Received: 20 May 2020

Accepted: 27 November 2020

Article published online:
12 April 2021

• References

• 1 Jess T, Rungoe C, Peyrin-Biroulet L. Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol 2012; 10: 639-645
• 2 Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001; 48: 526-535
• 3 Laine L, Kaltenbach T, Barkun A. et al. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastrointest Endosc 2015; 81: 489-501.e26
• 4 Laine L, Kaltenbach T, Barkun A. et al. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology 2015; 148: 639-651 e28
• 5 Sugimoto S, Naganuma M, Iwao Y. et al. Endoscopic morphologic features of ulcerative colitis-associated dysplasia classified according to the SCENIC consensus statement. Gastrointest Endosc 2017; 85: 639-646.e2
• 6 Farraye FA, Odze RD, Eaden J. et al. AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010; 138: 746-774 , 74 e1–4; quiz e12–3
• 7 Van Assche G, Dignass A, Bokemeyer B. et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. J Crohn Colitis 2013; 7: 1-33
• 8 Honmyo U, Misumi A, Murakami A. et al. Mechanisms producing color change in flat early gastric cancers. Endoscopy 1997; 29: 366-371
• 9 Kawamura M, Naganuma H, Shibuya R. et al. Analysis of microvascular density in early gastric carcinoma using magnifying endoscopy with narrow-band imaging. Endosc Int Open 2016; 4: E832-E837
• 10 Ohashi A, Niwa Y, Ohmiya N. et al. Quantitative analysis of the microvascular architecture observed on magnification endoscopy in cancerous and benign gastric lesions. Endoscopy 2005; 37: 1215-1219
• 11 Kinoshita S, Uraoka T, Nishizawa T. et al. The role of colorectal endoscopic submucosal dissection in patients with ulcerative colitis. Gastrointest Endosc 2018; 87: 1079-1084
• 12 Sugimoto S, Shimoda M, Iwao Y. et al. Intramucosal poorly differentiated and signet-ring cell components in patients with ulcerative colitis-associated high-grade dysplasia. Digest Endosc 2019; 31: 706-711
• 13 Shima T, Shimoda M, Shigenobu T. et al. Infiltration of tumor-associated macrophages is involved in tumor programmed death-ligand 1 expression in early lung adenocarcinoma. Cancer Sci 2020; 111: 727-738
• 14 Shimizu H, Shimoda M, Mochizuki S. et al. Hyaluronan-binding protein involved in hyaluronan depolymerization is up-regulated and involved in hyaluronan degradation in human osteoarthritic cartilage. Am J Pathology 2018; 188: 2109-2019
• 15 Riddell RH, Goldman H, Ransohoff DF. et al. Dysplasia in inflammatory bowel disease : standardized classification with provisional clinical applications. Human Pathology 1983; 14: 931-968
• 16 Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease : beyond discovery and development. Cell 2019; 176: 1248-1264
• 17 Chu PG, Weiss LM. Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon. Am J Clin Pathology 2004; 121: 884-892
• 18 Watanabe T, Ajioka Y, Mitsuyama K. et al. Comparison of targeted vs random biopsies for surveillance of ulcerative colitis-associated colorectal cancer. Gastroenterology 2016; 151: 1122-1130
• 19 Kawasaki K, Nakamura S, Esaki M. et al. Clinical usefulness of magnifying colonoscopy for the diagnosis of ulcerative colitis-associated neoplasia. Digest Endosc 2019; 31: 36-42
• 20 Shinagawa T, Hata K, Morikawa T. et al. Pine-cone and villi patterns are endoscopic signs suggestive of ulcerative colitis-associated colorectal cancer and dysplasia. Gastrointest Endosc 2019; 89: 565-575 e3
• 21 Kanesaka T, Uedo N, Yao K. et al. A significant feature of microvessels in magnifying narrow-band imaging for diagnosis of early gastric cancer. Endosc Int Open 2015; 3: E590-E596
• 22 Kaise M, Kato M, Urashima M. et al. Magnifying endoscopy combined with narrow-band imaging for differential diagnosis of superficial depressed gastric lesions. Endoscopy 2009; 41: 310-315
• 23 Gono K, Obi T, Yamaguchi M. et al. Appearance of enhanced tissue features in narrow-band endoscopic imaging. J Biomed Optics 2004; 9: 568-577
• 24 Efthymiou M, Allen PB, Taylor AC. et al. Chromoendoscopy versus narrow band imaging for colonic surveillance in inflammatory bowel disease. Inflamm Bowel Dis 2013; 19: 2132-2138
• 25 Pellise M, Lopez-Ceron M, Rodriguez de Miguel C. et al. Narrow-band imaging as an alternative to chromoendoscopy for the detection of dysplasia in long-standing inflammatory bowel disease: a prospective, randomized, crossover study. Gastrointest Endosc 2011; 74: 840-848
• 26 Scaldaferri F, Vetrano S, Sans M. et al. VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology 2009; 136: 585-595 e5
• 27 Chung AS, Ferrara N. Developmental and pathological angiogenesis. Ann Rev Cell Develop Biology 2011; 27: 563-584
• 28 Ravi R, Mookerjee B, Bhujwalla ZM. et al. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Develop 2000; 14: 34-44
• 29 Li AM, Boichard A, Kurzrock R. Mutated TP53 is a marker of increased VEGF expression: analysis of 7,525 pan-cancer tissues. Cancer Biol Ther 2020; 21: 95-100
• 30 Kanzaki H, Takenaka R, Kawahara Y. et al. Linked color imaging (LCI), a novel image-enhanced endoscopy technology, emphasizes the color of early gastric cancer. Endosc Int Open 2017; 5: E1005-E1013