Depressed lesion detected during surveillance colonoscopy in a patient with ulcerative colitis

Keijiro Numa; Kazuki Kakimoto; Noboru Mizuta; Naohiko Kinoshita; Kei Nakazawa; Ryoji Koshiba; Yuki Hirata; Ken Kawakami; Takako Miyazaki; Shiro Nakamura; Hiroki Nishikawa

doi:10.5217/ir.2025.00051

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Images of the Issue IBD Depressed lesion detected during surveillance colonoscopy in a patient with ulcerative colitis: Keijiro Numa, Kazuki Kakimoto, Noboru Mizuta, Naohiko Kinoshita, Kei Nakazawa, Ryoji Koshiba, Yuki Hirata, Ken Kawakami, Takako Miyazaki, Shiro Nakamura, Hiroki Nishikawa; Intestinal Research 2026;24(1):189-191.
DOI: https://doi.org/10.5217/ir.2025.00051
Published online: July 23, 2025

Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan

Correspondence to Kazuki Kakimoto, 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daiga-kumachi, Takatsuki 569-8686, Japan. E-mail: kazuki.kakimoto@ompu.ac.jp

• Received: April 2, 2025 • Revised: June 25, 2025 • Accepted: June 25, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Question: A 61-year-old man diagnosed 9 years ago with extensive ulcerative colitis (UC) and intolerance to mesalazine was treated with probiotics and maintained in long-term clinical remission. Levels of inflammatory markers, including white blood cells and C-reactive protein, as well as tumor markers, such as carcinoembryonic antigen and carbohydrate antigen 19-9, were within the normal range. A colonoscopy performed 1 year after the previous surveillance revealed a normal vascular pattern, characterized by clearly defined capillary arborization throughout the colon, indicating endoscopic remission. In contrast, a 15 mm depressed lesion with a slight peripheral elevation was observed in the sigmoid colon (Fig. A1). Chromoendoscopy with indigo carmine dye showed that most of the lesion was covered by normal mucosa with a central depression (Fig. A2). Narrow-band imaging magnification revealed an irregular surface pattern and moderately distorted vessels adjacent to the depression margin (Fig. B). No surface pattern was visible in the depressed area, and irregularities and discontinuities were observed in the blood vessels. Magnifying endoscopy with crystal violet staining revealed mildly irregular pit patterns at the margins of the depression and an absence of pit structure within the depressed area (Fig. C). Written informed consent was obtained. Based on the above information, what is the most likely diagnosis?

Answer to the Images: NEC Associated with Colitic Cancer

Endoscopic findings suggested either a submucosal tumor or early-stage colorectal cancer. A biopsy of the lesion was performed, and histopathological examination revealed a neuroendocrine neoplasm. However, due to the small volume of the tumor, precise histological classification was not possible. Therefore, endoscopic submucosal dissection (ESD) was performed as a diagnostic procedure. Histopathological examination revealed highly differentiated ductal adenocarcinoma at the margins of the ulcer in the center of the lesion, with low-grade dysplasia in the surrounding region (hematoxylin and eosin staining, ×10) (Fig. D). The submucosal layer was infiltrated by a mass of uniformly sized, round, small cancer cells forming small- to medium-sized full-blown foci. Adenocarcinomas and dysplasia in the mucosal layer were p53-positive, whereas the submucosal carcinoma mass was synaptophysin- positive, and the Ki-67 index was >20% (immunohistochemical staining, ×40). Based on these findings, neuroendocrine carcinoma (NEC) associated with colitic cancer was diagnosed. The patient was indicated for total proctocolectomy because of the presence of the complication of colitic cancer; however, laparoscopic sigmoidectomy with lymph node dissection was performed at the patient’s strong request. The surgical specimen showed no obvious tumor remnants, including lymph nodes; the final pathological stage of NEC was T1N0M0 (stage I).

Thereafter, UC remained in clinical remission, but metastatic lung tumor and lymph node appeared on a computed tomography scan 1 year after the surgery. A diagnosis of NEC recurrence was made, and chemotherapy was started with irinotecan (CPT-11) and cisplatin (CDDP). Chemotherapy resulted in temporary shrinkage of the tumor; however, the metastatic tumor subsequently increased in size, and the patient died approximately 4 years after ESD. NEC complications in patients with UC are rare, with only a few reported cases. Yokota et al. [1] reported 14 cases of UC combined with NEC, with a median age of onset of 54 years and a median disease duration of 16 years from diagnosis of UC to onset of NEC. The mechanism by which NEC occurs in patients with UC remains to be elucidated. However, approximately half of the patients with UC and NEC also have dysplasia or colitic cancer, suggesting a mechanism of differentiation from UC-associated neoplasia (UCAN) to NEC [2]. In the present case, the adenocarcinoma was located adjacent to the NEC, suggesting a carcinogenic mechanism involving a dysplasia–carcinoma sequence with subsequent differentiation into NEC. However, the possibility that the UCAN and NEC represent collision tumors, or that dedifferentiation from a sporadic adenocarcinoma to NEC occurred, cannot be ruled out. Further case series and molecular pathological studies are warranted to clarify these mechanisms.

The 2022 World Health Organization classification divides high-grade colorectal tumors into 3 categories according to the proportion of neuroendocrine and non-neuroendocrine tumors as follows: (1) NEC ( ≥30% neuroendocrine component and <30% non-neuroendocrine component); (2) mixed neuroendocrine non-neuroendocrine neoplasm ( ≥30% both components); (3) adenocarcinoma with neuroendocrine differentiation ( ≥30% adenocarcinoma and <30% neuroendocrine component) [3]. In this case, the tumor was classified as NEC. NEC associated with UC is mostly detected at stage III or IV with lymph node metastasis or distant metastasis. Because of its high malignant potential, many cases recur or metastasize within a short period of time after surgical treatment, and the prognosis is very poor. According to the 2021 NCCN clinical practice guidelines, adjuvant chemotherapy is recommended even for resectable colorectal NEC [4]. In contrast, the ENETS 2023 guidance paper discusses the significance of adjuvant chemotherapy based on the stage of colorectal NEC. They state that “Adjuvant chemotherapy may be considered for stage III cases and discussed individually for patients with stage II disease.” [5] However, in the present case, the patient experienced recurrence despite the NEC being classified as stage I. This highlights that even stage I NEC may carry a risk of early recurrence, suggesting that adjuvant chemotherapy should be considered even in such early-stage cases. The presence of colitic cancer further complicated the clinical course. Although partial resection of the sigmoid colon was performed in this patient, total proctocolectomy is generally recommended for UC patients who develop colorectal cancer. This recommendation is based on the elevated risk of synchronous and metachronous colorectal cancers in UC patients. In this case, however, no evidence of synchronous or metachronous carcinoma was found, and the adenocarcinoma in the sigmoid colon was treated with curative intent via partial resection. Nevertheless, the patient developed early recurrence postoperatively, which was due to NEC rather than adenocarcinoma. Thus, even if total proctocolectomy had been performed instead of partial sigmoidectomy, recurrence of NEC likely would not have been prevented. When UCAN is recognized, careful endoscopic observation and biopsy should be performed, bearing in mind that NEC may complicate and cause deep invasion. Even in early-stage NEC, the risk of recurrence is high, and multidisciplinary treatment, including adjuvant chemotherapy, should be considered. Accumulation of more such cases in the future is important to aid identification of risk factors that may predispose patients with UC to NEC.

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Funding Source

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Data Availability Statement

Not applicable.

Author Contributions

Conceptualization; Formal analysis; Methodology: Kakimoto K. Data curation: Numa K, Mizuta N, Kinoshita N, Nakazawa K, Koshiba R, Hirata Y, Miyazaki T, Nakamura S, Nishikawa H. Acquisition of endoscopic images: Kawakami K. Project administration; Supervision: Kakimoto K. Visualization: Kakimoto K, Kawakami K. Writing - original draft: Numa K, Kakimoto K. Writing - review & editing: Mizuta N, Kinoshita N, Nakazawa K, Koshiba R, Hirata Y, Kawakami K, Miyazaki T, Nakamura S, Nishikawa H. Approval of final manuscript: all authors.

REFERENCES

1. Yokota Y, Anzai H, Nagai Y, et al. Neuroendocrine carcinoma associated with chronic ulcerative colitis: a case report and review of the literature. Ann Coloproctol 2024;May;40(Suppl 1): S32–S37.Article PubMed PMC PDF
2. Lacerda-Filho A, da Mota FF, Lacerda GC, de Castro AF. Smallcell neuroendocrine carcinoma associated with non adenoma-like raised lesion in a patient with long-standing ulcerative colitis. J Crohns Colitis 2016;10:1125–1126.Article PubMed
3. WHO Classification of Tumours Editorial Board. WHO classification of tumours: endocrine and neuroendocrine tumours. Lyon: IARC, 2022.
4. Shah MH, Goldner WS, Benson AB, et al. Neuroendocrine and Adrenal Tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021;19:839–868.PubMed
5. Rinke A, Ambrosini V, Dromain C, et al. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for colorectal neuroendocrine tumours. J Neuroendocrinol 2023;35:e13309.PubMed

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Depressed lesion detected during surveillance colonoscopy in a patient with ulcerative colitis

Intest Res. 2026;24(1):189-191. Published online July 23, 2025

DOI: https://doi.org/10.5217/ir.2025.00051

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Depressed lesion detected during surveillance colonoscopy in a patient with ulcerative colitis

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Depressed lesion detected during surveillance colonoscopy in a patient with ulcerative colitis