Advanced colorectal adenoma (CRA) describes polyps with one of the following features: 1) size ≥ 10 mm, 2) villous component on histology, or 3) high-grade dysplasia.¹ Approximately 75% of colorectal cancers (CRCs) arise from adenomatous polyps and are in the adenoma-carcinoma pathway, and the advanced adenoma is estimated to progress to CRCs at a rate of 1% per year.^2,3 Therefore, these precancerous lesions or early-stage CRCs can be removed using appropriate endoscopic resection methods. With these treatment strategies, there have been few case reports of regression of advanced adenoma or early after immune checkpoint inhibitor (ICI)-based chemotherapy for other cancers. Herein, we report a case of regression of advanced adenoma or early after treating a patient with advanced gastric cancer (AGC).

A 58-year-old man without underlying disease underwent an esophagogastroduodenoscopy (EGD) at an outside hospital for cancer surveillance. The EGD showed an ulcerofungating mass on the upper third of the stomach, suggesting malignancy. He was referred for a diagnostic workup and cancer treatment. The laboratory results (complete blood count, liver function test, electrolyte levels, and serum creatinine measurements) were within the normal range. The EGD performed in our hospital revealed an approximately 4-cm ulcerofungating lesion on the posterior wall extending from high body to cardia. The pathologic diagnosis was moderately differentiated adenocarcinoma. A computed tomography (CT) scan of the abdomen and pelvis revealed known gastric cancer with suspected regional lymph node (LN) enlargement in the left gastric area. Positron emission tomography (PET)-CT showed AGC and regional LN metastasis in the left gastric area. The PET-CT scan showed a focal hypermetabolic lesion at the sigmoid colon. Colonoscopy revealed two polyps, one was located on the hepatic flexure, removed directly because that was a 4 mm-sized, benign-looking polyp. Finally, that polyp was reported as tubular adenoma with clear resection margin. And the other one was a 25-mm lesion compatible with the definition of a laterally spreading tumor (LST) with a nodular-mixed surface located in the rectosigmoid junction. The lesion showed a branch-like pit pattern on the white-light image, compatible with Kudo type IV.⁴ In the narrow-band image, the vascular pattern showed variable vessel caliber and irregular distribution. However, there was no obscure surface pattern (Fig. 1). The endoscopist suspected that the lesion was high-grade dysplasia or early CRC. She performed a biopsy and referred the patient to another specialist for en bloc resection. The biopsy revealed a villotubular adenoma with high-grade dysplasia (Fig. 2). The patient was finally diagnosed with AGC (cT4aN2Mx, stage IIIA, 8th American Joint Committee on Cancer edition)⁵ and advanced adenoma on the rectosigmoid junction. The oncologist decided to treat the AGC with neoadjuvant chemotherapy and planned to remove the LST by endoscopic resection after chemotherapy. The patient received three cycles of chemotherapy with durvalumab (ICI) plus platinum analog combination chemotherapy within two months. In the response evaluation, the cancer showed partial response,^6,7 and the patient were prepared for total gastrectomy. Before the surgery, he was hospitalized for an endoscopic removal of colonic LST. A subsequent colonoscopy aimed for treatment performed 3 months after the initial colonoscopy showed only hyperemic mucosal change at the rectosigmoid junction. To confirm the pathological diagnosis, endoscopic mucosal resection (EMR) was performed for hyperemic mucosal change, and the surface of the EMR ulcer showed fibrosis (Fig. 3). A pathologic report showed only scar change (Fig. 4).

Figure 1. Endoscopic findings of the laterally spreading tumor. (A) White-light endoscopy showing a 25 mm-sized laterally spreading tumor, with flat-elevated, nodular-mixed surface, located in 16 cm above the anal verge. White spot is noticed around the lesion. (B) Narrow-band image showing the brownish color change in the lesion with a gyrus-forming pattern in the background of normal-appearing colonic mucosa.

Figure 2. Histologic findings of the laterally spreading tumor. (A) Endoscopically biopsied specimen showing high-degree atypia (arrow), normal colonic mucosa and tubulovillous change (arrowhead) (H&E stain, ×10). (B) A leaf-like villous projections of dysplastic epithelium, the dysplastic tissue occupies less than 75% of the polyp area. Normal colonic mucosa is also seen (H&E stain, ×100). (C) High-grade dysplasia with significant nuclear pleomorphism (variation in shape/size), cribriform (arrow), loss of polarity and many mitoses is seen (H&E stain, ×200).

Figure 3. Endoscopic findings of the laterally spreading tumor after treatment of the advanced gastric cancer. (A) White-light endoscopy showing a scar change with white spots around the lesion. (B) Narrow-band image showing nearly normal-appearing colonic mucosa. (C) Artificial ulcer after endoscopic mucosal resection. Fibrosis is seen at the base of the ulcer (arrow).

Figure 4. Histologic features of the endoscopically resected specimen. (A) Endoscopically resected specimen showing collagenous fibers on the submucosa. Typical hypertrophy is not seen (H&E stain, ×20). (B) Myxoid degeneration (arrow) with unusual edema is seen (H&E stain, ×100).

The informed consent was waived.

In this case, the advanced CRA totally regressed after treating the AGC with ICI plus platinum analog. ICI possibly affects the achievement of regression by an immune response, and platinum-based chemotherapy, which has been widely used for CRC chemotherapy, could also influence the regression of advanced adenoma.⁸ Interestingly, ICI with platinum-based chemotherapy could treat gastric cancer with simultaneous regression of CRA or early CRC. Considering the mechanism by which ICI binds with immune cells and enables T cells to attack tumor cells, we presumed that ICI contributes to CRA regression more than cytotoxic agents. However, no study has evaluated the pharmacologic effects of each drug for CRA. Further preclinical research is necessary to prove the mechanism and identify the precipitating factors for regression of adenoma.

Subsequent studies should obtain additional data, such as the density of tumor-infiltrating lymphocytes or microsatellite instability (MSI) status, to elucidate the immune response of regression of CRA or early CRC.⁹ Our pathologic review observed unusual edematous change with myxoid degeneration in the resected specimen, probably related to immune response. Unfortunately, we could not perform immunohistochemistry staining for related immune markers and MSI tests due to cost considerations.

In conclusion, this case report describes regression of advanced CRA after treatment of other malignancy with ICI plus platinum analog. Our results suggest that precancerous lesions, such as adenomas, could be regressed by ICI. To our knowledge, this is the first report of regression of advanced CRA in Korea.

None.

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