Clin Endosc.  2024 Sep;57(5):637-646. 10.5946/ce.2024.027.

White spots around colorectal tumors are cancer-related findings and may aid endoscopic diagnosis: a prospective study in Japan

• Korekawa K
• Shimoyama Y
• Fujishima F
• Nagai H
• Naito T
• Moroi R
• Shiga H
• Kakuta Y
• Kinouchi Y
• Masamune A

• KMID: 2559215
• DOI: http://doi.org/10.5946/ce.2024.027

Abstract

Background/Aims
During endoscopy, white spots (WS) are sometimes observed around benign or malignant colorectal tumors; however, few reports have investigated WS, and their significance remains unknown. Therefore, we investigated the significance of WS from clinical and pathological viewpoints and evaluated its usefulness in endoscopic diagnosis.
Methods
Clinical data of patients with lesions diagnosed as epithelial tumors from January 1, 2019, to December 31, 2020, were analyzed (n=3,869). We also performed a clinicopathological analysis of adenomas or carcinomas treated with endoscopic resection (n=759). Subsequently, detailed pathological observations of the WS were performed.
Results
The positivity rates for WS were 9.3% (3,869 lesions including advanced cancer and non-adenoma/carcinoma) and 25% (759 lesions limited to adenoma and early carcinoma). Analysis of 759 lesions showed that the WS-positive lesion group had a higher proportion of cancer cases and larger tumor diameters than the WS-negative group. Multiple logistic analysis revealed the following three statistically significant risk factors for carcinogenesis: positive WS, flat lesions, and tumor diameter ≥5 mm. Pathological analysis revealed that WS were macrophages that phagocytosed fat and mucus and were white primarily because of fat.
Conclusions
WS are cancer-related findings and can become a new criterion for endoscopic resection in the future.

Keyword

Adenoma; Colorectal neoplasms; Colorectal tumors; Endoscopic diagnosis; White spots

Figure

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  Fig. 1. Flowchart of the review and analysis. Duplicate lesions from the same patient during the study period were excluded. “n” indicates the number of lesions, not the number of patients. WS, white spots. a)Difficult to evaluate because obtaining a whole image of the lesion was impossible owing to fecal matter or bleeding.

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  Fig. 2. Endoscopic findings of the white spot-positive colorectal epithelial tumor. (A) White spots are distributed around the whole circumference of early-stage colorectal cancer (sigmoid colon, T1b). (B) White spots are distributed around the adenoma (sigmoid colon, low-grade tubular adenoma). The patient provided oral informed consent for the publication and use of her/his images.

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  Fig. 3. Comparison of the positivity rate of white spots (WS) between proximal colon and distal colon. WS were more frequently present in the distal colon than in the proximal colon (Fisher exact test, *p<0.001). Proximal colon: cecum, ascending colon, and transverse colon. Distal colon: descending colon, sigmoid colon, and rectum.

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  Fig. 4. Positive rate of white spots according to tumor diameter. The positivity rate of white spots increased as tumor size became larger.

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  Fig. 5. Electron microscopic observations of white spots (WS). Electron microscopic examination of the WS revealed a cluster of macrophages in an area that appeared to coincide with the WS (the object surrounded by the dotted line represents a macrophage). Inside the cells, vacuolation, which is a result of fat denaturation, is present. a, nuclear; b, fat; c, lysosome; d, myelin body (possibly).

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  Fig. 6. Pathological staining image of white spots (WS). (A) The specimen was excised through endoscopic submucosal dissection, and the WS was observed on the lateral side. Magnified observation revealed that the area corresponding to the WS aligned with the substance was deposited spherically just below the epithelium (arrows). (B) Hematoxylin and eosin (H&E) staining (×100): Histiocytes are clustered immediately below the epithelium in the area consistent with the gross magnified image of WS (corresponding to the area surrounded by the dotted line). (C) Periodic acid–Schiff (PAS) staining (×100): The same area where a cluster of histiocytes was observed in H&E staining was positive (corresponding to the area surrounded by the dotted line). (D) Immunohistochemistry (IHC) with anti-adipophilin antibody (×100): IHC was performed by diluting the antibody to 1/50, and the area matching the H&E and PAS stain-positive areas was considered positive (corresponding to the area surrounded by the dotted line).

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  Fig. 7. Changes in endoscopically resected tumors with white spots (WS) over time. (A) Colonoscopy (CS) of endoscopic mucosal resection: The lesion was resected with sufficient endoscopic margins; however, the WS remained in the mucosa (corresponding to the area surrounded by the dotted line). The pathological diagnosis in this case was pTis, cN0, cM0, and G1; pStage 0 (Union for International Cancer Control 8th edition), and both the horizontal and vertical margins were negative. No lymphovascular invasion was observed, and the patient was cured using endoscopic resection. (B) CS at 1.5 years after treatment: The resection area was scarred (corresponding to the area surrounded by the dotted line), and the WS had disappeared.

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