Small Submucosal Adenocarcinoma Curatively Resected by Minimally Invasive Treatment in the Third Portion of the Duodenum

A 74-year-old man presented with nonspecific symptoms. His previous doctor found an 8-mm-diameter polypoid lesion in the third portion of the duodenum by screening endoscopy. A biopsy showed a low-grade adenoma, and the patient was referred to our hospital for treatment. White light endoscopy showed a partial milky-white color change [1] in the small lesion (Figure 1a). Indigo carmine chromoendoscopy showed a clear demarcation line without irregularities. Magnifying endoscopy with narrow-band imaging (ME-NBI) demonstrated high-density mucosal patterns characterized by heterogeneity in shape and size, as well as dilated vascular patterns exhibiting irregular bending and changes in caliber (Figure 1b). Based on these findings, high-grade adenoma or mucosal adenocarcinoma of an intestinal type was suspected. The lesion was removed using en bloc endoscopic mucosal resection (EMR). The nonlifting sign were not observed, and no findings suggestive of submucosal invasion were seen during EMR (Figure 1c). Histological analysis revealed a dense proliferation of atypical glands in the mucosal and submucosal layers, with an obscured vertical margin owing to thermal coagulation (Figure 2a). High-power microscopy demonstrated irregularly branching tubular structures with disruption of nuclear polarity, consistent with tubular adenocarcinoma (Figure 2b). Immunohistochemical staining for desmin confirmed muscularis mucosal disruption and submucosal invasion of ≥ 500 μm (Figure 2c). Immunohistochemistry showed that the tumor cells were positive for MUC2 and CD10, while negative for MUC5AC and MUC6, indicative of an intestinal-type adenocarcinoma. Histological examination of the EMR specimen revealed no lymphovascular invasion, with a negative horizontal margin. Additional surgery, minimally invasive sentinel-node navigation surgery (SNNS), was performed because the tumor showed submucosal invasion and the vertical margin could not be assessed owing to thermal effects. Sentinel lymph nodes were identified using local injection of indocyanine green solution near the EMR scar, which revealed lymphatic flows through laparoscopic infrared imaging. Four sentinel lymph nodes were detected and removed; intraoperative rapid pathological diagnosis revealed no cancer metastasis. Subsequently, partial duodenal resection was performed without adverse events (Figure 1d). Histologically, no residual cancer cells were observed in the surgical specimens. No recurrence or metastasis occurred during the 6-year postoperative follow-up. We found that 10 cases of submucosal cancer measuring ≤ 10 mm have been reported in the literature. To our knowledge, no case of small submucosal cancer < 10 mm and located in the third portion of the duodenum has previously been reported. This case highlights that the distal duodenum (the third or fourth portion) can harbor a small submucosal cancer lesion, and it is not possible to predict submucosal cancer invasion because a preoperative biopsy specimen was diagnosed as low-grade adenoma. Endoultrasonography (EUS) was not performed in this case since using EUS to predict the depth of duodenal cancer invasion is not well-established, and performing EUS in the third portion would be very difficult or impossible. In this case, ME-NBI findings revealed irregularities in the surface structure and vascular patterns of the mucosa, suggesting the possibility of high-grade adenoma or mucosal adenocarcinoma. However, the surface structures of the mucosa were preserved and showed no evidence of disruption or nonstructural areas suggesting submucosal cancer invasion. Therefore, we removed this lesion using EMR rather than cold snare polypectomy (CSP). CSP has become widely used for small duodenal lesions (≤ 10 mm); however, specimens resected using CSP do not include the submucosal tissue. Thus, information about the histology of the submucosal layer cannot be obtained with CSP specimens. Therefore, CSP is clearly indicated for adenoma and contraindicated for lesion suspected of cancer which had potential of submucosal invasion [2]. Based on this, CSP for superficial nonampullary duodenal epithelial tumors should be limited to lesions that are endoscopically diagnosed as adenoma ≤ 10 mm, and EMR should be performed for lesions ≤ 10 mm but are thought to be mucosal cancer, as in this case. The lymph node metastasis rate for duodenal submucosal cancer ranges from 5% to 11% [3]. Despite the relatively low risk of metastasis, pancreaticoduodenectomy—a highly invasive surgery, particularly for older adults in cases such as this—remains the standard treatment for submucosal cancer in the duodenum. However, considering the patient's age and the small size of the submucosal cancer, pancreaticoduodenectomy was considered excessively invasive in this case. Hence, we performed a partial duodenectomy using the special technique SNNS. The patient experienced no postsurgical adverse events and has shown an excellent postoperative course for over 5 years. SNNS may be a minimally invasive option alternative to pancreaticoduodenectomy for small submucosal cancer in the duodenum. In conclusion, we report a case of small submucosal adenocarcinoma in the third portion of the duodenum that was difficult to diagnose preoperatively but was curatively treated using EMR followed by SNNS. We thank Mamoru Ito, Naoya Tada, and Jumpei Yamamoto for their technical assistance and valuable discussions. All authors declare no conflicts of interest.