Gastric Adenocarcinoma Resembling Submucosal Tumor: A Case Report

Introduction

Submucosal tumors (SMTs) are usually asymptomatic and are often discovered incidentally during routine gastroscopy. Gastric SMTs include a diverse array of benign, potentially malignant, and malignant lesions, including gastrointestinal stromal tumors (GISTs), leiomyomas, neuroendocrine tumors, lipomas, granular cell tumors, varices, duplication cysts, heterotopic pancreas, Brunner gland hamartoma, lymphangiomas, and endometriosis [1]. Gastric cancer with features of submucosal tumor (GCSMT) is generally a protuberant lesion covered with normal mucosa and is exceedingly rare, with a prevalence estimated to be as low as 0.1% to 0.62% of all gastric cancers [2].

Case Report

A 60-year-old man presented to our hospital with a chief concern of stomach discomfort for 2 months. He had no history of Helicobacter pylori eradication or any antacid medication, such as proton pump inhibitors. On physical examination, the abdomen was soft and flat with no palpable mass or tenderness. No peripheral lymphadenectasis was observed. Five days prior to admission, the patient received a gastroscopy examination. The result showed a tumor 2.0 cm in diameter located at the lesser curvature of the stomach resembling a SMT, chronic atrophic gastrokeratitis with intestinal metaplasia, duodenal bulbtis, and antral ulcer (Figure 1). The tumor was covered by normal gastric mucosa. To clarify the nature of the tumor, the patient further underwent an endoscopic ultrasonography (EUS) examination and 13C-urea breath test. The result of 13C-urea breath test was negative. The EUS displayed a 2.0×0.8-cm, well-defined, hypo-echogenic mass arising from the muscular layer in the stomach wall, which strongly suggested a GIST (Figure 2). The patient was then admitted to our internal digestive ward for further endoscopic treatment.

His laboratory parameters were normal, including the tumor markers carcinoembryonic antigen (1.94 ng/mL) and carbohydrate antigen 19-9 (0.73 U/mL). The contrast-enhanced computed tomography (CT) scan also demonstrated a well-circumscribed, exophytic, SMT in the lesser curvature of the upper stomach, which was enhanced at the arterial phase (Figure 3).

Based on these findings, endoscopic submucosal dissection (ESD) was performed to resect the tumor (Figure 4). The resected specimen was 2.0×2.0 cm in size and a gray-white nodule in the submucosa. Histopathologic examination demonstrated poorly differentiated adenocarcinoma, and Epstein-Barr virus infection in the cancer tissue could not be demonstrated (Figure 5). Immunohistochemical staining showed positive expression for cytokeratin (CK), CK7 (partial), CK8/18, caudal-type homeobox 2 (CDX-2) (partial), villin, and Ki-67 (approximately 50%), and negative expression for synaptophysin (Syn), thyroid transcription factor-1 (TTF-1), CD56, CD34 (Figure 5C). Because no obvious abnormal tissues or cells were found in the mucosa, and the carcinoma was confined to the submucosa, we speculated that there were no mucosal lesions present. Additionally, histological examination did not reveal any characteristic features typically seen in other conditions, such as mucin aggregation in mucinous adenocarcinoma, lymphocyte infiltration in lymphoepithelioma-like carcinoma, or glandular expansion in the submucosa and muscular layer as seen in gastritis cystica profunda. Therefore, the origin of the tumor was not clear. To clarify whether there was metastasis, the patient then underwent positron emission computed tomography (PET-CT), and the result revealed gastric malignancy. Accordingly, subtotal gastrectomy with regional lymph node dissection was performed. Finally, the postoperative specimen showed firm nodules were palpable in the lesser and greater curvatures of the stomach, and pathology examination confirmed the diagnosis of poorly differentiated adenocarcinoma, with infiltration to the muscular layer. Macroscopic stagings according to the TNM classification was T2N0M0, grade IB [3]. Postoperative pathologic examination revealed the specimen had clear margins, indicating complete resection of the tumor. Moreover, follow-up CT and upper gastrointestinal endoscopy were scheduled for after the surgery.

Discussion

To elucidate the clinical characteristics of GCSMTs, we reviewed 21 cases published in English, including the present case (Table 1) [2,4–21]. The cases included 14 male patients (66.67%) and 7 female patients (33.33%), ranging in age from 40 to 81 years, with an average age of 58 years. Five patients (23.81%) had preoperative histological diagnosis established by ESD, and the diagnostic methods mentioned included endoscopic biopsy, endoscopic mucosal resection, ESD, EUS-guided fine needle aspiration (FNA), laparoscopic biopsy, and postoperative biopsy. Histological diagnoses included well-differentiated adenocarcinomas in 19.05% (4/21) of cases, moderately differentiated adenocarcinoma in 4.76% (1/21), poorly differentiated adenocarcinomas in 38.10% (8/21), mucinous adenocarcinomas in 19.05% (4/21), signet ring gastric carcinomas in 9.52% (2/21), and lymphoepithelioma-like gastric carcinomas in 9.52% (2/21). Unexpectedly, more than half of the patients had no obvious clinical symptoms, as their tumors were detected through routine health evaluation.

GCSMT is a malignant tumor, and its treatment typically requires systemic gastrectomy with en bloc lymphadenectomy, a treatment approach that differs significantly from that used for other SMTs [22]. Preoperative pathologic diagnosis can be helpful in clinical decision-making. However, a preoperative diagnosis is difficult to make, because most GCSMTs are covered with nearly normal mucosa [5]. Many techniques have been used in attempts to obtain adequate samples for tissue diagnosis of SMTs, including EUS-FNA, EUS-guided trucut biopsy (TCB), endoscopic boring biopsy, biopsy after mucosal incision to expose the tumor, endoscopic submucosal tumorectomy, and biopsy after resection of the mucosa [1]. EUS has been used for diagnosis of SMTs for more than a decade and is considered the most accurate procedure for detecting and diagnosing SMTs owing to its high sensitivity and specificity [23]. Although EUS-FNA and EUS-TCB are reliable diagnostic methods for SMTs, their diagnostic accuracy is influenced by many factors, with sampling adequacy and diagnostic rates reported to be 74% to 83% and 71% to 83%, respectively. Additionally, the amount of tissue sample obtained by FNA is small, which increases the number of needle passes [17]. Repeated EUS-FNA can also cause metastasis of malignant tumors. The 5 cases we reviewed, including our case, were diagnosed by ESD, which has a reported diagnosis rate of almost 90% [23] and can not only improve the diagnosis rate but also remove the whole tumor, reducing the possibility of metastasis.

SMTs can be treated with various endoscopic techniques, including endoscopic mucosal resection, endoscopic band ligation, ESD, endoscopic submucosal enucleation, endoscopic full-thickness resection, and endoscopic submucosal tunneling dissection [1]. ESD can be used both to obtain biopsy specimens for pathological diagnosis and for the treatment of SMTs. However, pathological diagnosis is often unavailable before ESD. Of note, once biopsy specimens for diagnosis are obtained through ESD, the patient’s treatment plan can change significantly. Therefore, before ESD, it is necessary to fully communicate with patients and inform them of possible follow-up treatment plans.

Conclusions

In our patient, the result of gastroscopy, EUS, and contrast-enhanced CT suggested a GIST; however, with the use of ESD, the final diagnosis was gastric adenocarcinoma. Based on our experience, in cases of potentially malignant SMTs, we suggest that although many examinations – such as serum tumor markers, CT, PET-CT, and EUS – can aid diagnosis, biopsy specimen acquisition should still be performed proactively, because the treatment strategy for GCSMTs is completely different from that for other gastric SMTs. Our case shows that for SMTs of an unclear nature, ESD can not only serve as a treatment but also provide biopsy tissue for pathological diagnosis to aid in making a definitive diagnosis. Finally, since SMTs can be malignant, thorough communication with patients is essential when developing treatment plans.