Inflammation-Masked Sporadic Colorectal Cancer Detected After Remission Induction in Elderly-Onset Ulcerative Colitis

ABSTRACT

A 73-year-old patient with newly diagnosed ulcerative colitis (UC) presented with pancolitis and no detectable neoplastic lesion at initial colonoscopy. After remission induction with corticosteroids and maintenance therapy with azathioprine, follow-up colonoscopy 1 year later revealed a 10 mm 0-IIa + IIc lesion in the ascending colon. Endoscopic submucosal dissection demonstrated well-differentiated adenocarcinoma with submucosal invasion. No dysplasia was identified in the surrounding mucosa, and p53 overexpression was confined to the tumor, a finding more compatible with a sporadic phenotype than with colitis-associated neoplasia.

This case suggests that active inflammation may have masked a preexisting colorectal neoplastic lesion, highlighting the importance of colonoscopic reassessment after remission induction in elderly-onset UC.

INTRODUCTION

Patients with ulcerative colitis (UC) are at increased risk of colorectal neoplasia.^1–3 Active mucosal inflammation may impair visualization of subtle lesions and delay diagnosis. We report a case of elderly-onset UC in which a sporadic colorectal cancer became detectable only after remission induction, suggesting an inflammation-related masking effect.

CASE REPORT

A 73-year-old man was referred to our hospital because of a positive fecal occult blood test. He presented with hematochezia and mild diarrhea without abdominal pain, fever, or weight loss. Laboratory examination revealed a white blood cell count of 7,220/μL, hemoglobin of 13.8 g/dL, albumin of 4.3 g/dL, and C-reactive protein of 3.88 mg/dL. Colonoscopy demonstrated continuous diffuse erythema, erosions, and exudates extending from the rectum to the cecum, consistent with pancolitis (Mayo Endoscopic Score 2; Figure 1). Bowel preparation was considered adequate for complete examination of the colon, and no neoplastic lesion was identified. Histopathological examination of biopsy specimens showed marked lymphocytic infiltration of the lamina propria with cryptitis and crypt abscesses, accompanied by glandular distortion, consistent with chronic active UC (corresponding to Matts grade 4).

Figure 1.

Initial colonoscopy showing active pancolitis with diffuse erythema, erosions, and exudates extending from the rectum to the cecum.

Mesalamine (2,400 mg/day) was initiated but discontinued because of drug intolerance characterized by high fever and worsening abdominal pain. Corticosteroid therapy (prednisolone 30 mg/day) induced rapid clinical remission. Because the patient preferred oral maintenance therapy, azathioprine (50 mg/day) was initiated after discussion of potential risks and benefits.

One year later, follow-up colonoscopy performed during sustained remission revealed a 10 mm elevated and depressed lesion (0-IIa + IIc) in the ascending colon (Figure 2). Magnifying endoscopy with blue laser imaging demonstrated a JNET type 2B pattern (Figure 3), and crystal violet chromoendoscopy showed a mildly irregular type VI pit pattern (Figure 3). Endoscopic submucosal dissection was performed.

Figure 2.

Follow-up colonoscopy revealing a 10 mm 0-IIa + IIc lesion.

Figure 3.

Magnifying endoscopy findings of the lesion. (A) Blue laser imaging demonstrates a JNET type 2B pattern. (B) Crystal violet chromoendoscopy shows a mildly irregular type VI pit pattern.

Histopathological examination demonstrated well-differentiated tubular adenocarcinoma with submucosal invasion to a depth of 1,310 μm (Figure 4). No lymphovascular invasion (Ly0, V0) or high-grade tumor budding was identified. Both horizontal and vertical margins were negative. Importantly, no dysplasia was observed in the surrounding mucosa, and p53 overexpression was confined to the tumor. Additional surgical resection was subsequently performed because of the depth of submucosal invasion and confirmed the absence of residual tumor and lymph node metastasis.

Figure 4.

(A–C) Histopathological findings of the endoscopic submucosal dissection specimen. (A) Hematoxylin and eosin staining shows a well-differentiated tubular adenocarcinoma with irregular glandular structures accompanied by adenomatous gland proliferation. No dysplastic changes are identified in the adjacent nonneoplastic mucosa (40×, left; 200×, right). (B) Desmin staining highlights disruption of the muscularis mucosae and confirms submucosal invasion to a depth of 1,310 μm (arrow) (200×, left; 40×, right). (C) Immunohistochemical staining for p53 demonstrates overexpression confined to the tumor, while the surrounding nonneoplastic mucosa shows no abnormal staining. These findings are more compatible with a sporadic phenotype than with the field cancerization typically observed in colitis-associated neoplasia (40×, left; 200×, middle; 200×, right).

DISCUSSION

This case illustrates the potential for active inflammation to mask colorectal neoplasia in UC. At the time of diagnosis, moderate pancolonic inflammation was present and no neoplastic lesion was identified. After remission induction, a small colorectal cancer became clearly detectable, suggesting that active inflammation may have obscured the lesion during the initial colonoscopy. Previous studies have shown that persistent inflammatory activity is associated with colorectal neoplasia and may complicate lesion detection.⁴

An additional important finding was the distinction between sporadic colorectal cancer and colitis-associated neoplasia. In the present case, the depth of submucosal invasion was 1,310 μm, exceeding the 1,000 μm threshold that is generally regarded as deep submucosal invasion. According to the European Society of Gastrointestinal Endoscopy guideline and the United States Multi-Society Task Force recommendations, additional surgical resection with lymph node dissection should be considered because of the increased risk of lymph node metastasis.^5,6 The absence of residual tumor and lymph node metastasis in the surgical specimen confirmed the appropriateness of this management strategy. The lesion was localized and well demarcated, without dysplasia in the surrounding mucosa. Furthermore, p53 overexpression was confined to the tumor and was absent in adjacent nonneoplastic tissue. Taken together, these clinicopathological findings are more compatible with a sporadic colorectal neoplasm than with colitis-associated neoplasia. However, p53 immunostaining alone cannot distinguish these entities because its diagnostic role remains controversial and should therefore be interpreted in conjunction with the overall clinicopathological findings.^7–9

This observation may be particularly relevant in elderly-onset UC. In older patients, sporadic colorectal neoplasia may already be present at or near the time of UC diagnosis. When active inflammation obscures mucosal details, such lesions may remain undetected until remission is achieved. Although it cannot be determined whether the carcinoma was already present at the initial examination, active inflammatory changes may have obscured a subtle lesion. Therefore, clinicians should maintain awareness of coexisting neoplasia in elderly patients with newly diagnosed UC.

This concept is consistent with the recent European Crohn's and Colitis Organization, the European Society of Gastrointestinal and Abdominal Radiology, the European Society of Pathology, and the International Bowel Ultrasonography Group Guidelines, which recommend repeat endoscopic evaluation after resolution of active inflammation when dysplasia is suspected, because accurate histological assessment may be difficult in severely inflamed mucosa.¹⁰ Although our patient had no visible dysplastic lesion at the initial examination, this case illustrates that active inflammatory changes may also obscure subtle neoplastic lesions. Our findings suggest that colonoscopic reassessment after remission induction may be useful when the initial examination is limited by active inflammation. Current surveillance recommendations mainly address long-term surveillance in established UC, whereas evidence regarding early colonoscopic reassessment after remission induction remains limited. Nevertheless, our case supports careful reevaluation after mucosal healing, particularly in elderly patients with newly diagnosed UC in whom preexisting sporadic neoplasia may have been obscured by active inflammation.^11–13

Although the optimal timing remains uncertain, reassessment following remission may improve the detection of clinically significant neoplastic lesions. Because the diagnostic value of p53 immunohistochemistry remains controversial, the distinction between sporadic and colitis-associated neoplasia should be based on the overall clinicopathological findings rather than p53 staining alone.

In conclusion, active inflammation may obscure preexisting colorectal neoplastic lesions in elderly-onset UC; therefore, colonoscopic reassessment after remission induction may facilitate earlier detection of clinically significant neoplasia.

DISCLOSURES

T. Tanaka contributed to study conception, patient management, data collection, manuscript preparation, and final approval of the manuscript. All authors contributed to clinical management, manuscript review, and final approval of the submitted version. T. Tanaka is the article guarantor.

Acknowledgements: The authors would like to thank Mohei Kouyama, MD, PhD, Kosei Kitamura, MD, and Songde Cho, MD, PhD, for their valuable contributions to the clinical care of the patient.

Financial disclosure: None to report.

Informed consent was obtained for this case report.

ABBREVIATIONS:

UC

ulcerative colitis

JNET

Japan NBI (Narrow Band Imaging) Expert Team