Revisiting the distinct histomorphologic features of inflammatory bowel disease–associated neoplastic precursor lesions in the SCENIC and post–DALM Era

Gui, Xianyong; Iacucci, Marietta; Ghosh, Subrata; Ferraz, José G.; Lee, Scott

doi:10.1016/j.humpath.2020.04.010

Cited by 7 publications

(3 citation statements)

References 29 publications

(38 reference statements)

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“…In addition to classic/conventional dysplastic lesions [1][2][3][4][5][6][7], several "non-conventional" atypical lesions or growths have been reported to be associated with (and likely precede) cancer development in IBDs of both large and small intestine [12,19,30,49,50]. We also found such lesions in the mucosa overlying or adjacent to CrD-SBC; indeed, in seven cases, these were in direct continuity with cancer tissue and sometimes with patterns suggestive of direct transition.…”

Section: Discussionsupporting

confidence: 52%

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn’s disease-associated small bowel carcinoma

et al. 2021

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Most Crohn’s disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies.

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Section: Discussionsupporting

confidence: 52%

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn’s disease-associated small bowel carcinoma

et al. 2021

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“…In a recent review of the different histologic features associated with carcinoma in IBD, Gui and colleagues underlined that colitis-associated dysplasia exhibited a mixed/intermingled with inflammatory pseudopolyps and/or granulation tissue [ 28 ], revealing a histologic overlap and confirming the difficult to differentiate the lesions.…”

Section: Discussionmentioning

confidence: 99%

Frequency and Predictors of Dysplasia in Pseudopolyp-like Colorectal Lesions in Patients with Long-Standing Inflammatory Bowel Disease

De Cristofaro,

Lolli,

Migliozzi

et al. 2023

Cancers

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Current endoscopic surveillance programs do not consider inflammatory bowel disease (IBD)-associated post-inflammatory polyps (pseudopolyps) per se clinically relevant, even though their presence seems to increase the risk of colorectal cancer (CRC). However, it remains unclear whether the link between pseudopolyps and CRC is indirect or whether some subsets of pseudopolyp-like lesions might eventually undergo neoplastic transformation. This study aimed to assess the frequency and predictors of dysplasia in pseudopolyp-like lesions in a population with long-standing colonic IBD. This was a retrospective, single-center study including patients with a colonic IBD (median disease duration of 192 months) and at least a pseudopolyp-like lesion biopsied or resected in the period from April 2021 to November 2022. One hundred and five pseudopolyps were identified in 105 patients (80 with ulcerative colitis and 25 with Crohn’s disease). Twenty-three out of 105 pseudopolyp samples (22%) had dysplastic foci, and half of the dysplastic lesions were hyperplastic. Multivariate analysis showed that the age of the patients (odds ratio (OR) 1.1; p = 0.0012), size (OR 1.39; p = 0.0005), and right colonic location (OR 5.32; p = 0.04) were independent predictors of dysplasia, while previous exposure to immunosuppressors/biologics and left colonic location of the lesions were inversely correlated to dysplasia (OR 0.11; p = 0.005, and OR 0.09; p = 0.0008, respectively). No differences were seen between ulcerative colitis and Crohn’s disease patients. Lesions with a size greater than 5 mm had a sensitivity of 87% and a specificity of 63% to be dysplastic. These data show that one-fourth of pseudopolyp-like lesions evident during surveillance colonoscopy in patients with longstanding IBD bear dysplastic foci and suggest treating such lesions properly.

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“…Colorectal dysplasia can be defined as a neoplastic alteration of the intestinal epithelium that remains confined within the basal membrane [ 27 ]. Dysplastic lesions show specific morphological features, such as nuclear alterations, cytoplasmic abnormalities and an abnormal architectural pattern due to uncontrolled cell proliferation [ 28 , 29 ]. In IBD-associated cancer, there is a multi-step sequence of histological and morphological changes, namely from inflamed mucosa to low-grade dysplasia (LGD), high-grade dysplasia (HGD) and eventually carcinoma ( Figure 1 ) [ 30 ].…”

Section: Ibd-associated Cancer: From Inflamed Tissue To Carcinomamentioning

confidence: 99%

The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

Frigerio

Lartey

D’Haens

et al. 2021

IJMS

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Patients with inflammatory bowel disease (IBD) have increased incidence of colorectal cancer (CRC). IBD-associated cancer follows a well-characterized sequence of intestinal epithelial changes, in which genetic mutations and molecular aberrations play a key role. IBD-associated cancer develops against a background of chronic inflammation and pro-inflammatory immune cells, and their products contribute to cancer development and progression. In recent years, the effect of the immunosuppressive microenvironment in cancer development and progression has gained more attention, mainly because of the unprecedented anti-tumor effects of immune checkpoint inhibitors in selected groups of patients. Even though IBD-associated cancer develops in the background of chronic inflammation which is associated with activation of endogenous anti-inflammatory or suppressive mechanisms, the potential role of an immunosuppressive microenvironment in these cancers is largely unknown. In this review, we outline the role of the immune system in promoting cancer development in chronic inflammatory diseases such as IBD, with a specific focus on the anti-inflammatory mechanisms and suppressive immune cells that may play a role in IBD-associated tumorigenesis.

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Revisiting the distinct histomorphologic features of inflammatory bowel disease–associated neoplastic precursor lesions in the SCENIC and post–DALM Era

Cited by 7 publications

References 29 publications

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn’s disease-associated small bowel carcinoma

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn’s disease-associated small bowel carcinoma

Frequency and Predictors of Dysplasia in Pseudopolyp-like Colorectal Lesions in Patients with Long-Standing Inflammatory Bowel Disease

The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

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