A case of late lymph node metastasis after three endoscopic mucosal resections of intramucosal gastric cancers

In Japan, the Gastric Cancer Treatment Guidelines (GCTGs) (ver. 3) define absolute indications for endoscopic resection (ER), which include ≤20-mm intramucosal differentiated cancers without an ulcer[1]. Curative resection is restricted to en bloc resection in the latest guideline[1]. However, before the GCTGs were established, piecemeal resection was considered to be curative when the specimen was completely reconstructed and showed negative lymphovascular invasions and horizontal/vertical margins[2]. We experienced a rare late recurrence case of lymph node (LN) metastasis after endoscopic mucosal resections (EMRs) including a piecemeal resection that were curative on the basis of the GCTGs criteria at that time[1‐3].

A 62-year-old man was admitted in 1998 because early gastric cancer (EGC) was detected by annual screening endoscopy. There was no specific finding in the physical examination or laboratory data. He had no medical history of malignant tumors. The lesion was a 10-mm type 0-IIc moderately differentiated adenocarcinoma without an ulcer located at the lesser curvature of the antrum (Figure 1a). We diagnosed that this lesion had a negligible risk of LN metastasis, and ER was indicated[4]. We explained to the patient that EMR was an investigational treatment at that time, and he chose to receive EMR instead of surgery. EMR using piecemeal resection was performed, which was curative macroscopically. The specimens were completely reconstructed, and pathological examination confirmed a 10-mm type 0-IIc moderately differentiated adenocarcinoma, without an ulcer (Figure 1b). The tumor was confined to the mucosa with negative lymphovascular invasions and horizontal/vertical margins, which indicated that the resection was curative according to the Japanese 13th edition of the Classification of Gastric Carcinoma[2]. We performed endoscopy at 1, 3, and 6 months after EMR to check for local recurrence, and every biopsy of the EMR scars revealed no malignancy. Thereafter, we performed follow-up endoscopy and abdominal ultrasonography (AUS) to check locoregional or distant metastasis every year, and no recurrence was detected. After 10 years, another lesion was detected by endoscopy in 2008 when the patient was 72 years old. The lesion was a 12-mm type 0-IIa moderately differentiated adenocarcinoma without an ulcer located at the anterior wall near the pylorus (Figure 1c). En bloc EMR was performed; pathological examination revealed a 12-mm type 0-IIa lesion without an ulcer that was predominantly a moderately differentiated adenocarcinoma with papillary adenocarcinoma components (Figure 1d). The tumor was confined to the mucosa with negative lymphovascular invasions and horizontal/vertical margins, which indicated that the resection was curative according to the GCTG (ver. 2)[3]. Thereafter, we performed follow-up endoscopy and AUS every year; recurrence was not observed, but a nonrecurrent lesion was detected in 2011 when the patient was 75 years old. The lesion was a 7-mm type 0-IIa + IIc moderately differentiated adenocarcinoma without an ulcer, located at the greater curvature of the antrum (Figure 1e). En bloc EMR was performed; pathological examination revealed a 1-mm moderately differentiated adenocarcinoma without an ulcer (Figure 1f). The tumor was confined to the mucosa with negative lymphovascular invasions and horizontal/vertical margins. However, the tumor seemed to invade into the muscularis mucosa, which indicated that the resection was curative (GCTGs, ver. 3)[1]. Although subsequent endoscopy did not detect recurrence, a 20-mm tumor was detected along the lesser curvature of the stomach by screening AUS in 2013 when the patient was 77 years old (Figure 2a). We performed computed tomography (CT) and positron emission tomography (PET)-CT. CT showed a 20-mm tumor along the lesser curvature of the stomach and no other metastatic lesion (Figure 2b). PET-CT showed 18 F-fluorodeoxyglucose hot uptake in the same lesion (Figure 2c). We performed endoscopy to check for new lesions or local recurrence. The endoscopy showed three lesions on EMR scars and an elevated lesion displaced from the outside at the lesser curvature of the upper stomach that had not been detected at the last endoscopy (Figure 3a-d). We performed biopsies of each EMR scar and the elevated lesion, but no malignancy was identified. Gastrointestinal stromal tumor (GIST), carcinoid tumor, and lymphoma were considered in the differential diagnosis along with LN metastasis. Although endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) was considered to determine a pathological diagnosis, EUS-FNA was not performed because of the risk of dissemination. We performed a laparoscopic total excisional biopsy to resect the tumor, and the intraoperative frozen section indicated LN metastasis of the adenocarcinoma (Figure 4a). Because this LN was recognized as #3a LN with stomach invasion, the operation was converted to an open standard total gastrectomy with D1 LN dissection. Postoperative pathological examination indicated that the resected LN was a metastasis of the moderately differentiated adenocarcinoma with stomach wall invasion (Figure 4b-d). Additionally, no remnant or recurrent malignancy was detected at any stomach EMR site, and no other metastasis was found among the 52 other LNs retrieved.

This case presents a rare case of late LN metastasis after EMR based on the indications for endoscopic treatment of gastric cancer. This case might represent a limitation of ER in evaluating LN status. Because piecemeal resection has a risk of not only local recurrence but also of LN metastasis, en block resection is required, and careful follow-up is mandatory.

Written informed consent for publication of this case report and any accompanying images was obtained from the patient. A copy of the written consent is available for review by the Editor-in-Chief of this journal.