Esophageal carcinoma is a highly aggressive digestive cancer responsible for a notable proportion of cancer-related deaths worldwide. Its elevated metastatic rate contributes to a poor prognosis in affected patients. In this case review, we aim to summarize the metastatic characteristics of intramural gastric metastasis (IGM) in mucosal esophageal squamous carcinoma.

A 56-year-old man was admitted to our hospital because of a dry cough with an esophageal sensation for one year. Endoscopic examination revealed a 2.0 cm 1.0 cm, superficial esophageal squamous cell carcinoma, and the patient underwent endoscopic submucosal dissection (ESD). Fifteen months after ESD, positron emission tomography/computed tomography revealed that the metabolism of the stomach cardia wall had increased slightly. However, the mucosa of the gastric cardia was smooth under gastroendoscopy. Two years after ESD, endoscopic examination revealed a giant gastric cardia carcinoma, while the esophageal mucosa was smooth, and no advanced cancer was found. A biopsy of the gastric cardia indicated squamous-cell carcinoma. The patient received immunochemotherapy and radiotherapy for esophageal cancer for 8 mo and is currently under follow-up.

Early-stage esophageal carcinoma with IGM is rare. Despite the ESD of the primary lesion, IGM may still occur and should be closely monitored after ESD.

Globally, esophageal squamous cell carcinoma (SCC) (ESCC) is the sixth leading cause of cancer-related deaths. In Asian countries, SCC is the most common pathological type of esophageal cancer. The prognosis of ESCC is poor owing to its increased tendencyfor direct spread and metastasis. The 5-year survival rate of ESCC patients with metastatic disease is less than 5%[1]. ESCC often metastasizes to the lymph nodes and distant organs, and intramural metastasis (IM) occasionally occurs, which is seen in approximately 10% of esophageal carcinomas[2,3]. IM is a form that tumor can occur as a skip lesion in the other parts of esophagus or to the stomach. IM incidence in ESCC in the head and neck is 25%, compared with 11% in stage I ESCC[4]. However, the reported intramural gastric metastasis (IGM) is seldom, accounting for only 1%–4.58% of ESCC through surgical treatment[5-9]. A higher incidence of IGM has been reported in the advanced ESCC, whereas only a few cases of IGM have been reported in the early-stage ESCC[10-13]. Herein, we report a case of mucosal esophageal carcinoma with multi-pathway and multi-organ metastases (including IGM, lymphatic metastasis of celiac lymph nodes, and hematogenous metastasis of the liver and right adrenal gland) that occurred in a metachronous manner, while the IGM progressed rapidly over 1 year. We hope that this case will guideclinicians in identifying unique metastasis of ESCC in some cases when making a treatment plan.

The patient was diagnosed as early-stage esophageal carcinoma with giant gastric cardia metastasis.

To alleviate the observed multi-organ metastasis, the patient was administered immunochemotherapy (carrelizumab 200 mg D1, albumin paclitaxel 400 mg D1, and carboplatin 450 mg D1) and radiotherapy (30 courses) for esophageal cancer. Six immunochemotherapy and 30 radiotherapy courses were completed.

The development and treatment of the disease in the present case are summarized in Figure 6.

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Figure 6 Summary of disease development and treatment of the present case.

The immunochemotherapy and radiotherapy was completed and the patient was still alive. The follow-up is ongoing.

ESCC is an extremely aggressive cancer and has a poor prognosis owing to its higher propensity for lymph nodes and distant metastases. Historically, cancer-distal metastases are considered as the most important barrier to achieving significant advances in cancer management; moreover, it is responsible for 90% of cancer-related deaths[14,15]. The incidence of distant metastases in newly diagnosed ESCC is approximately 20%–30%. However, this proportion raised to approximately 40%–50% in recurrent cases after radical esophagectomy[16] or concurrent radiochemotherapy[17] in ESCC. IM is another metastasis pathway in esophageal cancer. Based on previous endoscopic findings, clinical IM, including gastric metastasis from ESCC, had mainly three characters: (1) Metastatic tumor often separated distantly from the primary tumor; (2) The metastatic lesion presented in the esophagus or stomach wall; and (3) the SMT lacked of an intraepithelial component, occasionally with an erosive change[6]. Accompanied by these findings, the ESCC strongly suggests an IM tumor[18].

Longitudinal lymphatic vessels contained in the mucosa lamina propria and submucosa of the esophagus are the anatomic basis for IM[19]. The mucosal lymphatic channels in esophagus are not directly connected to those in stomach; however, submucosal channels may have a direct connection with the submucosal gastric lymphatics[20]. Therefore, tumor cells go through the submucosal lymphatic system to the stomach wall and form metastatic loci[20]. Watson and Goodner[21] first reported there existed an interflow of lymphatic channels between the esophagus and stomach through virtue of neo-lymphangiogenesis in the carcinomatous lesion and explained IM as an extension of submucous lymphatics. Kato et al[6] documented that the location of the IM toward the primary tumor did not indicate a predilection in the direction of the lymphogenic spread of carcinoma of the esophagus. However, another study[5] showed that among 1259 patients, although the depth of esophageal cancer may be T1, the possibility of IGM still exists. The incidence of IGM is higher in advanced-stage ESCC[5,22], as only a few cases of IGM in the early-stage ESCC have been reported. From mucosal ESCC, to our best knowledge, only 6 cases (including the present one) have been documented[10-13,23]. Therefore, although the probability of lymphatic metastasis is very low, it can still occur even if the tumor is confined to the mucosa.

IGM from esophageal cancer is rare[5,9]; nonetheless, it is considered to be one of the most significant poor prognostic factors due to its higher rate of lymphatic invasion[24,25] and distant metastasis. The correlation between metastatic tumors and lymph node metastasis can be attributed to the fact that gastric metastases occur via the lymphatic system. In the middle and lower parts of the esophagus, submucosal lymphatic drainage is regarded to be connected to gastric from the cardia and fundus. At times, the primary esophageal lesion could appear to be small, compared with the gastric metastatic lesion, which is exophytic in morphology because of the submucosal site of implantation[22]. In this report, the primary tumor was in the middle-thoracic esophagus, and the IGM was found in the gastric cardia.

In addition, IGM plays a role in distant metastasis, particularly in the liver[6]. IGM of ESCC is categorized as distant metastasis, described as M1b stage IVB, according to the Union for International Cancer Control for International Cancer Control Classification[26]. However, other studies have reported metastases in the reconstructed stomach. IGM develops principally in the upper third of the stomach wall; however, it can also appear in the gastric body[5,9]. These mean IGM happen without direct involvement of the lymphatic system[27]. In this report, the tumor cells giving rise to IGM could not have spread via the lymphatic system because the primary tumor was confined to the mucosa with no lymphatic connection to the submucosa. Thus, IGM sometimes develops via routes other than the lymphatic system, including vascular routes. In addition, we found multiple distant metastases to the liver and right adrenal gland, which indicated that there were hematogenous pathways of metastasis in our case.

In our case, what really surprised us was that from November 2021 (PET-CT suggested abnormal cardiac metabolism) to November 2022 (gastroendoscopy revealed a Borrmann type II lesion in the cardiac area), metastases to the cardia grew rapidly and were so large that no significant primary lesions were found in the esophagus. The cardiac area is rich in blood supply, which is conducive to the root proliferation of squamous cells, and the cardiac area is significantly large[23,24]. Primary gastric adenocarcinoma sometimes has a similar gross appearance but a higher incidence in the lower part of the stomach. Gastrointestinal stromal tumors also appear as exophytic lesions. The detection rate of IM of ESCC ranges 5.5% between 16.6%[6,28]. General endoscopy has certain limitations when the metastases are confined below the mucosa without breaking through the surface. The radiological imaging, especially fluorodeoxyglucose-PET, can detect out early metastatic lesions in time[29-31]. Therefore, preoperative and postoperative radiographic follow-up is conducive to indicating the presence of IM[20,32]. The five-year disease-free survival rate of patients with ESCC with IM is significantly lower than that of patients without IM[6,33]. Therefore, multimodal treatments with strong antitumor effects should be administered.

In conclusion, preoperative and postoperative endoscopic follow-up of patients with ESCC of any stage, although the depth of an esophageal cancer may be T1, in addition to paying attention to esophageal lesions, the stomach should also be carefully examined, especially for the submucosal eminence in the upper part of the stomach, to consider the possibility of IGM, and the nature of the submucosal eminence can be clarified by combining endoscopic ultrasonography and ultrasonic puncture biopsy. Therefore, enhancing the preoperative and postoperative imaging and endoscopic ultrasonography are beneficial for indicating the existence of IM.