The endoscopic features of gastric MALT lymphoma can be classified into exophytic, ulceroinfiltrative, and superficial types; ulceroinfiltrative type is the most common, accounting for approximately 40–50% of all cases [14-17]. Yokoi et al. categorized the superficial types of gastric MALT lymphoma into IIc-like, submucosal tumor, multiple erosion, cobblestone mucosa, partial fold-thickening, and discoloration types [18]. Gastric MALT lymphoma may be missed during esophagogastroduodenoscopy (EGD) because its endoscopic features are variable and nonspecific. Therefore, this condition needs to be considered when abnormal mucosa is observed during this procedure (Fig. 1).

Endoscopic biopsy using forcep and histopathologic examination are the most basic tests for diagnosis of gastric MALT lymphoma. However, false-negative results in the histologic examination may be possible because the tumor cell of gastric MALT lymphoma originates from the deep mucosa or submucosa and grows without destroying the foveolar gland, which is the basic structure of the mucosal surface [19,20]. Therefore, repeated EGD and endoscopic biopsy may be needed for accurate diagnosis of gastric MALT lymphoma. Furthermore, because gastric MALT lymphoma may have a multifocal distribution of tumors and high-grade gastric MALT lymphoma may be present together, multiple endoscopic biopsies should be performed in the normal mucosa of the antrum, greater and lesser curvatures of the body, and fundus, as well as the abnormal mucosa of at least two tissues in each part [21]. More invasive tissue biopsy such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) may be required if the diagnosis is not confirmed by endoscopic biopsy [22].

Lymphoepithelial lesion is characteristic feature of gastric MALT lymphoma. Wotherspoon et al. [23] proposed a histological classification system to differentiate normal gastric mucosa and gastric MALT lymphoma (Table 1). Gastric MALT lymphoma can be diagnosed if a histopathologic change corresponding to a score of 5 is observed. If the score is 3 or 4, diagnosis is confirmed based on the monoclonality of B-cells in polymerase chain reaction (PCR) [24]. In addition to morphological evaluation of the tissues, immunohistochemical staining of cluster of differentiation (CD) 20, CD79a, CD43, and more can be performed to diagnose gastric MALT lymphoma. A balanced translocation, t(11;18)(q21;q21), is found in 25–30% of gastric MALT lymphoma cases [25], and it was shown to be associated with a low response to H. pylori eradication therapy and poor prognosis [26,27]. Moreover, t(11;18)(q21;q21) assessed by fluorescence in situ hybridization or API2/MALT1 fusion gene, which is the result of chromosomal translocation, detected by reverse transcriptase PCR, can identify the patients who are expected to have low therapeutic response to H. pylori eradication therapy.

Confirming H. pylori infection in gastric MALT lymphoma is important because the presence of H. pylori affects treatment strategy and response. H. pylori infection must be detected by rapid urease test, histological examination, culture test, urea breath test, and stool antigen test [28], and the presence of H. pylori should be confirmed during the histopathologic evaluation for the diagnosis of gastric MALT lymphoma. Because hematoxylin and eosin staining has low sensitivity for H. pylori diagnosis and has difficulty in detecting non-spiral and spherical H. pylori, special stainings, such as Giemsa, Warthin–Starry, and Alcian blue, or immunostaining for H. pylori, which is the most sensitive and specific, may be required to confirm H. pylori infection [29,30].

Recently, several studies have been reported to improve the diagnosis of gastric MALT lymphoma by using imaging-enhanced endoscopy, such as narrow-band imaging or linked color imaging [31,32].

Endoscopic ultrasonography (EUS), which has sensitivity of 89%, a specificity of 97%, and a total accuracy of 97%, is the most accurate test to assess the depth of tumor invasion of gastric MALT lymphoma [33,34]. EUS is also useful for evaluating local lymph node metastasis. EUS findings of gastric MALT lymphoma can be classified into four types: superficially spreading, diffusely infiltrating, mass forming, and mixed. Superficially spreading and diffusely infiltrating types are seen in low-grade gastric MALT lymphoma, and tumor invasion into the whole gastric wall and lymph node enlargement are characteristics of high-grade gastric MALT lymphoma [35].

EUS can be used to diagnose gastric MALT lymphoma. A thickened gastric wall of 6–12 mm in the EUS can predict gastric MALT lymphoma, and EUS–guided fine needle aspiration (EUS–FNA) can provide diagnostic information by securing false negatives that may occur in endoscopic biopsy [36,37].

EUS can help predict the treatment response of gastric MALT lymphoma. When the gastric MALT lymphoma infiltrates into the submucosal layer in EUS, the complete remission rate for H. pylori eradication therapy is lower than that for the mucosal layer. When the tumor invades the muscle layer, complete remission was not achieved by H. pylori eradication therapy [38,39] (Fig. 2).

After the treatment of gastric MALT lymphoma, therapeutic response or relapse after the remission could be evaluated by tracking the changes in the gastric wall thickness by EUS [40]. However, even when remission is achieved, normalization of the thickened gastric wall occurs slowly, and EUS may show normal findings even if the tumor remains histologically [41]. Nevertheless, if thickened stomach wall is observed on EUS even after sufficient time has elapsed since treatment of gastric MALT lymphoma, the possibility of residual gastric MALT lymphoma cannot be ruled out, albeit normal histopathologic examination results [35].