1. Introduction
Gastric lymphoma arising from mucosa-associated lymphoid tissue (MALT) was first reported as a low-grade gastric lymphoma in 1983 by Isaacso [1] . MALT lymphoma has distinct histological and clinical characteristics compared with nodal B-cell lymphoma [1] -[3] . MALT lymphoma arising in the stomach grossly presents as a flat, superficial, or even invasive lesion with erosions and ulcerations, and develops from chronic active gastritis. Gastric MALT lymphoma is often misdiagnosed endoscopically as a gastric ulcer, gastritis, or gastric cancer, and it is necessary to establish the diagnosis of gastric MALT lymphoma from these diseases. It is important to initially suspect gastric MALT lymphoma because of the various macroscopic patterns, even when multiple biopsies cannot yield a definitive diagnosis of MALT lymphoma.
It was reported that 10% - 20% of cases on initial endoscopy and 50% - 70% of cases on biopsies were diagnosed as MALT lymphoma [4] . One of the reasons for misdiagnosis might be the low incidence of stomach MALT lymphoma, that is, 2% - 8%, within gastric malignant disease [5] .
There are few organized reports on the endoscopic findings of gastric MALT lymphoma [6] -[8] , with only a few case reports published on its diverse endoscopic findings [9] -[11] . Recent studies have reported the usefulness of NBI magnifying endoscopy in diagnosing gastric MALT lymphoma [12] -[15] . In addition, the usefulness of endoscopic ultrasound findings as a predictor of the therapeutic efficacy of H. pylori eradication has been reported [16] [17] . In this review, we summarize these reports, and report the endoscopic diagnosis of gastric MALT lymphoma.
2. Conventional Endoscopy
The conventional endoscopic findings of gastric MALT lymphoma vary widely, ranging from ulcerative or gastritis-like lesions to those resembling depressed early gastric cancer, or elevated lesions (Figure 1). In some cases, more than one gross pathologic type of gastric MALT lymphoma coexists in the same stomach. There are also case reports of patients presenting with multiple lymphomatous polyposis (MLP), which is often observed in mantle cell lymphoma [9] [11] . Zullo et al. [6] classified gastric MALT lymphoma into ulcerative, exophytic, hypertrophic, mixed, petechial hemorrhage, and normal/hyperemic types. In Japan, gastric MALT lymphoma has been classified into early-stage gastric carcinoma-like, gastritis-like, and submucosal tumor-like patterns [14] [18] ; into superficial (including superficial ulcer, erosion, gastritis, discolored area, early cancer-like, and cobblestone types), mass, and mixed types [15] ; and into superficial and SMT-like types [19] .
However, it is not easy to classify the wide variety of endoscopic findings by type.
The common conventional endoscopic findings of H. pylori eradication-resistant gastric MALT lymphioma were elevated submucosal lesions [20] . If the remission of gastric MALT lymphoma is achieved after H. pylori eradication or irradiation, endoscopy reveals a scar (Figure 2).
3. Narrow Band Imaging
Narrow band imaging (NBI) is a new image enhancement system employing optic digital methods to enhance images of blood vessels on mucosal surfaces, allowing the improved visualization of mucosal surface structures. Studies have progressed over the last several years, and the clinical usefulness has been demonstrated [21] [23] .
In 2009, we reported a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma presenting with unique vascular features [12] . In the report, we defined the tree-like appearance (TLA) on the images of abnormal blood vessels which resembled branches from the trunk of a tree in the shiny mucosa, in which the glandular structure was lost (Figure 3). Norimura et al. also reported similar findings in 2012 [24] .
Figure 1. Various endoscopic findings of gastric MALT lymphoma. (A) Gastritis-like pattern; (B) SMT-like pattern; (C) Early gastric cancer-like pattern; (D) Ulcer-like pattern.
Figure 2. Changes in findings of MALT lymphoma on conventional endoscopy after successful eradication therapy. Scars with fold convergence were formed after successful eradication therapy.
Figure 3. We defined the tree-like appearance (TLA) on the images of abnormal blood vessels which resembled branches from the trunk of a tree in the shiny mucosa, in which the glandular structure was lost.
TLA observed in gastric MALT lymphoma is useful for differentiation from undifferentiated-type early gastric cancer and gastritis, which is difficult by conventional observation 21.
Therefore, we have clearly shown that target biopsies from a suspected MALT lymphoma based on ME with NBI are useful in the histological diagnosis of gastric MALT lymphoma 13.
As experience with patient treatment increased, we found that gastric MALT lymphoma without TLA existed, with the result that TLA was observed in 75% of gastric MALT lymphomas 14. In that study, H. pylori eradication therapy was performed in 12 patients showing TLA to examine the relationship between changes in NBI findings and the efficacy of H. pylori eradication.
TLA disappeared in all 8 patients in whom no residual MALT lymphoma was observed on biopsy after therapy, whereas TLA remained in all 4 patients in whom residual MALT lymphoma was noted on biopsy (p = 0.002), showing that the sensitivity and specificity were 100%.
NBI magnifying endoscopy is an essential means of diagnosing gastric MALT lymphoma.
4. Endoscopic Ultrasonography
Nakamura et al. [16] considered that evaluation of the depth of SM invasion by endoscopic ultrasonography (EUS) was useful for the prediction of the efficacy of H. pylori eradication therapy: the remission rate was 93% in patients diagnosed with mucosal (M) lesions by EUS, whereas it was only 23% in those with submucosal (SM) or deeper lesions (Figure 4). EUS was also reported to be useful for determining the healing of gastric MALT lymphoma [25] .
Figure 4. Endoscopic ultrasonography findings of gastric MALT lymphoma. A) Conventional endoscopy revealed an ulcerative lesion with fur in the greater curvature of the upper gastric corpus; B) EUS showed that the fourth layer was obscured, suggesting that MALT lymphoma had invaded the muscular and deeper layers.
5. Conclusion
Although further studies involving more patients are needed, the use of NBI, which has been reported to be useful in the endoscopic diagnosis of gastrointestinal tumors over the last several years, has enabled the diagnosis of gastric MALT lymphoma with a high degree of accuracy. The endoscopic appearances of gastric MALT lymphoma are so varied that it is undoubtedly difficult to establish a diagnosis by conventional endoscopy alone.
To make a definitive diagnosis of gastric MALT lymphoma, it is essential to include gastric MALT lymphoma first in the differential diagnoses of lesions identified by conventional endoscopy, particularly when multiple and variable gastric lesions are observed. It is recommended that NBI magnifying endoscopy be performed at the time of suspicion of gastric MALT lymphoma to select an appropriate biopsy site. At present, EUS findings alone can be used to predict the therapeutic efficacy of H. pylori eradication; therefore, it is recommended that EUS be performed, whenever possible, for the pretreatment evaluation of gastric MALT lymphoma. Needless to say, it is necessary for gastric MALT lymphoma to be comprehensively diagnosed by a combination of conventional endoscopy and diagnostic aids, such as NBI and EUS, and treated.
NOTES
*Corresponding author.