Intest Res.  2024 Oct;22(4):428-438. 10.5217/ir.2024.00006.

Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy

• Sakakibara R
• Sugimoto S
• Takabayashi K
• Kiyohara H
• Wakisaka Y
• Kaieda Y
• Kawaida M
• Yoshimatsu Y
• Sujino T
• Hosoe N
• Kato M
• Shimoda M
• Mikami Y
• Iwao Y
• Kanai T

• KMID: 2560293
• DOI: http://doi.org/10.5217/ir.2024.00006

Abstract

Background/Aims
Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features.
Methods
This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component.
Results
Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%).
Conclusions
This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.

Keyword

Colitis-associated neoplasms; Dysplasia; Colorectal neoplasms

Figure

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  Fig. 1. Flow of patients through the study. One hundred and one of 110 patients with ulcerative colitis (UC) and HGD/adenocarcinoma were enrolled and divided into a group with por/sig/muc components (n=35; Group P) and a group without por/sig/muc components (n=55; Group T) and HGD (n=11). The Group P was subdivided according to whether it contained more por/sig/muc components (n=20) or more tub components (n=15). HGD, high-grade dysplasia; por, poorly differentiated adenocarcinoma; sig, signet-ring cell carcinoma; muc, mucinous adenocarcinoma; tub, tubular adenocarcinoma.

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  Fig. 2. Kaplan-Meier survival curves for patients after diagnosis of ulcerative colitis-associated neoplasms. (A) Cumulative survival of all patients with adenocarcinoma in the por/sig/muc (Group P) and tub (Group T) groups. (B, C) Cumulative survival rates for patients in the Group T (B) and Group P (C) divided into stages 0–II, III, and IV. (D) Cumulative survival rates of patients with a tumor depth of at least subserosa divided into Group P and Group T. por, poorly differentiated adenocarcinoma; sig, signet-ring cell carcinoma; muc, mucinous adenocarcinoma; tub, tubular adenocarcinoma.

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  Fig. 3. Lesion histology according to targeted biopsy diagnosis, SCENIC classification, and staging. (A) Discrepancies in the final histologic diagnosis in each resected specimen diagnosed as dysplasia, tub, or por/sig/muc on biopsy. Only cases of identifiable lesions in which both targeted biopsy and resection pathology information were available were analyzed. (B) Proportion of lesions according to the SCENIC classification defined by colonoscopy with final histologic diagnosis. (C) Comparison of the proportions of histologic types of lesions at each disease stage. tub, tubular adenocarcinoma; por, poorly differentiated adenocarcinoma; sig, signet-ring cell carcinoma; muc, mucinous adenocarcinoma; HGD, high-grade dysplasia.

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  Fig. 4. Representative endoscopic and histologic findings in the Group P. (A) Images of CAC in the Group P, which are classified in the same SCENIC classification category but have markedly different tumor depths. Lesions with at least a portion depressed below the level of the mucosa were presented as depressed lesions. (B, C) Representative H&E staining (B) and p53 immunostaining (C) of CAC (right top panel, Fig. 4A) with sig (left bottom panel) and tub (right bottom panel) tumor histology differing by site because of intratumoral heterogeneity. (D, E) Representative H&E staining (D) and p53 immunostaining (E) of CAC (left bottom panel, Fig. 4A) which is difficult to detect from the surface but has a por component infiltrating to the subserosa. Inset shows higher magnification. CAC, colitis-associated neoplasia; Group P, por/sig/muc group; por, poorly differentiated adenocarcinoma; sig, signet-ring cell carcinoma; muc, mucinous adenocarcinoma; tub, tubular adenocarcinoma; H&E, hematoxylin and eosin.

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