ABSTRACT
Primary esophageal extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) is extremely rare, and its optimal management has not been established. We report a case of primary esophageal MALT lymphoma that was successfully treated by endoscopic submucosal dissection (ESD). A 70‐year‐old woman presented with an elevated lesion in the lower esophagus that was detected incidentally on computed tomography. Endoscopy and endoscopic ultrasonography revealed a subepithelial lesion confined to the submucosal layer without apparent invasion of the muscularis propria. Although an endoscopic biopsy suggested a low‐grade lymphoma, a definitive diagnosis could not be established because of the limited tissue volume. Therefore, ESD was performed to obtain an adequate specimen for definitive diagnosis, and complete resection was achieved as a result. Histopathological and immunohistochemical examinations of the resected specimen confirmed primary esophageal MALT lymphoma. The patient has remained in complete remission for 3 years without additional therapy. This case suggests that ESD may be a diagnostic and therapeutic option for primary esophageal MALT lymphoma.
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Keywords: B‐cell, biopsy, endoscopic submucosal dissection, endoscopy, esophageal neoplasms, lymphoma, marginal zone
1. Introduction
Extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) is an indolent primary extranodal B‐cell lymphoma that frequently arises in the gastrointestinal tract, particularly in the stomach [1]. Primary involvement of the esophagus is rare. Although therapeutic strategies for gastric MALT lymphoma, including Helicobacter pylori eradication, radiotherapy, and systemic chemotherapy, have been well established [2], the optimal management of primary esophageal MALT lymphoma remains to be established.
Herein, we report a patient with primary esophageal MALT lymphoma who was successfully treated by endoscopic submucosal dissection (ESD) and has remained in complete remission for 3 years.
2. Case Report
A 70‐year‐old woman had undergone periodic upper and lower gastrointestinal endoscopic examinations. She was referred to our hospital after multiple colorectal polyps were detected on colonoscopy. She had no gastrointestinal symptoms, such as dysphagia or weight loss. During the initial evaluation, an elevated lesion in the lower esophagus was detected incidentally on computed tomography, warranting further endoscopic examination. Colonoscopy revealed multiple laterally spreading tumors and sessile polyps extending from the ascending colon to the cecum. Because complete identification and endoscopic assessment of all lesions were considered difficult, laparoscopic right hemicolectomy was performed. Histopathological examination of the resected specimen showed tubular adenomas, with no evidence of lymphoma. A physical examination revealed no abnormal findings. Laboratory tests revealed a serum lactate dehydrogenase level of 170 U/L, a serum soluble interleukin‐2 receptor level of 323 U/mL, and negativity for serum anti‐H. pylori antibodies. 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG‐PET/CT) demonstrated focal metabolic activity confined to the lower esophagus (Figure 1A). Esophagogastroduodenoscopy showed a smooth, elevated subepithelial lesion in the lower thoracic esophagus (Figure 2A). The main lesion extended between the 6 and 9 o'clock positions, and a separate, similar whitish lesion with slight elevation was observed at the 4 o'clock position (Figure S1A; arrowheads, main lesion; arrows, separate similar lesion). Mid‐ to long‐distance narrow‐band imaging is shown in Figure 2B, with an additional view provided in Figure S1B. Figure 2C shows magnifying narrow‐band imaging of the area indicated by the yellow square in Figure 2B. The magnifying narrow‐band imaging revealed mildly dilated intrapapillary capillary loops without significant atypia (Figure 2C). Endoscopic ultrasonography revealed a hypoechoic submucosal mass that was predominantly located within the submucosal layer without apparent invasion of the muscularis propria (Figure 2D, arrow).
FIGURE 1.
18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG‐PET/CT). (A) Pretreatment 18F‐FDG‐PET/CT revealed focal metabolic uptake confined to the lower esophagus. (B) Follow‐up 18F‐FDG‐PET/CT performed at 3 months after endoscopic submucosal dissection demonstrated a complete metabolic response.
FIGURE 2.
Endoscopic and endoscopic ultrasonography findings. (A) Esophagogastroduodenoscopy showed a smooth, elevated subepithelial lesion in the lower thoracic esophagus. (B) Mid‐ to long‐distance narrow‐band image. (C) Magnifying the narrow‐band image of the area indicated by the yellow square in panel B. The magnifying narrow‐band image showed mildly dilated intrapapillary capillary loops without significant atypia. No definite background coloration was observed. (D) Endoscopic ultrasonography demonstrated a hypoechoic submucosal mass that was predominantly located within the submucosal layer.
Based on the endoscopic and imaging findings, the differential diagnosis included benign submucosal tumors, such as leiomyoma, and malignant lesions, such as lymphoma. Although an endoscopic biopsy suggested a low‐grade lymphoma, a definitive diagnosis could not be established because of the limited tissue volume. Because a definitive histopathological diagnosis was required and the lesion appeared to be confined to the submucosal layer, the patient underwent ESD. During the procedure, a submucosal injection and mucosal incision led to inversion of the lesion, revealing a yellowish‐white submucosal tumor (Figure 3A). A submucosal dissection was then performed, exposing the submucosal layer (Figure 3B), and the lesion was resected en bloc (Figure 3C). Because approximately three‐quarters of the esophageal circumference was resected, triamcinolone was locally injected into the ulcer base to reduce the risk of postoperative stricture. Pathological analysis of the resected specimen revealed infiltration of small‐to‐medium lymphoid cells with a vague nodular pattern (Figure 4A,B). The horizontal and vertical margins were free of lymphoma. On immunohistochemical examination, the lymphoid cells were positive for CD20 (Figure 4C), Bcl‐2, and MNDA (Figure 4D) and negative for CD3, CD5, CD10, Bcl‐6, cyclin D1, and MUM1. Based on these findings, the patient was diagnosed with primary esophageal MALT lymphoma. The disease was classified as Lugano stage I [3] and was categorized as low risk according to the MALT lymphoma prognostic index [4].
FIGURE 3.
Endoscopic submucosal dissection (ESD) procedure and follow‐up findings. (A) After mucosal incision, the lesion became inverted, revealing a yellowish‐white submucosal tumor. (B) Submucosal layer after partial resection. (C) Resected specimen obtained by en bloc ESD. (D) Follow‐up endoscopy performed at 6 months after the ESD procedure showed no evidence of a residual lesion.
FIGURE 4.
Histopathological findings of the resected specimen. (A, B) Infiltration of small‐to‐medium lymphoid cells with a vague nodular pattern was observed on hematoxylin and eosin staining (A, ×4; B, ×40). (C, D) Immunohistochemical staining revealed lymphoid cells that were positive for CD20 (C, ×40) and MNDA (D, ×40).
At 3 months after the ESD procedure, 18F‐FDG‐PET/CT confirmed a complete metabolic response (Figure 1B). At 6 months, a follow‐up endoscopy revealed no residual lesion (Figure 3D). The patient has remained in complete remission for 3 years.
3. Discussion
Primary esophageal lymphoma is extremely rare, accounting for less than 1% of primary gastrointestinal lymphomas [5]. Because of its rarity, no standard therapeutic approach has been established. In the present case, ESD enabled both definitive diagnosis and complete resection of primary esophageal MALT lymphoma. The patient has remained in complete remission for 3 years without additional therapy.
Primary esophageal MALT lymphoma often presents as a subepithelial or submucosal lesion, making a definitive diagnosis by standard endoscopic biopsy difficult. In the present case, the main lesion was located in the lower thoracic esophagus. Previous reports of esophageal MALT lymphoma cases have described variable tumor locations within the esophagus, with several cases involving the middle‐to‐lower esophagus [6, 7]. In previously reported cases of primary esophageal lymphoma, ulcerative or infiltrative endoscopic appearances were more frequently described for aggressive histological subtypes, such as diffuse large B‐cell lymphoma, while MALT lymphoma was often described as a subepithelial or submucosal lesion with intact mucosa [6]. Because tumor cells predominantly infiltrate the submucosal layer, a standard forceps biopsy may yield insufficient tissue for accurate histopathological evaluation and subclassification. In the present case, although an endoscopic biopsy suggested a low‐grade lymphoma, the limited tissue volume hindered a definitive diagnosis. Endoscopic ultrasonography was useful for evaluating the tumor depth and excluding invasion of the muscularis propria, but could not provide a histological confirmation. Endoscopic ultrasound‐guided fine‐needle aspiration has been proposed as a diagnostic approach for esophageal MALT lymphoma [8]. However, it only provides limited tissue architecture for comprehensive pathological assessment. In the present case, ESD enabled the acquisition of an adequate specimen for precise pathological assessment and achieved complete resection.
Reported treatments for primary esophageal MALT lymphoma have included surgical resection, radiotherapy, systemic chemotherapy, H. pylori eradication, and endoscopic resection [7, 9, 10]. Most reported patients had localized disease at diagnosis. Among the treatment options, only a few patients have been treated by endoscopic resection [10]. In those cases, endoscopic mucosal resection or ESD achieved complete resection and favorable outcomes, and the follow‐up periods ranged from 1 to 3 years without documented recurrence. In the present case, the lesion was confined to the submucosal layer with no invasion of the muscularis propria. ESD allowed en bloc resection with tumor‐free margins, and the patient has remained disease‐free for 3 years without additional therapy. These findings suggest that ESD may represent a potential diagnostic and therapeutic option for primary esophageal MALT lymphoma.
In conclusion, primary esophageal MALT lymphoma is a rare clinical entity for which optimal management remains to be established. The present case suggests that for localized disease confined to the submucosal layer without apparent invasion of the muscularis propria, ESD may provide a definitive diagnosis and result in complete resection. Accumulation of additional cases with long‐term follow‐up is required to further clarify the role of endoscopic resection in the management of primary esophageal MALT lymphoma.
Author Contributions
Junya Makiyama: conceptualization, data curation, investigation, and writing – original draft. Hiroko Fukuda: investigation, data curation, and writing – review & editing. Kyoko Minamino: writing – review & editing. Yukiyoshi Moriuchi: writing – review & editing. Koichi Ohshima: pathological diagnosis validation, and writing – review & editing. All authors approved the final version of the manuscript.
Funding
The authors have nothing to report.
Ethics Statement
Institutional review board approval: N/A.
Consent
Written informed consent for publication of the case details and images was obtained from the patient.
Conflicts of Interest
Junya Makiyama reports consulting fees from Daiichi Sankyo and Janssen Pharmaceutical; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AbbVie GK, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Genmab, Janssen Pharmaceutical, Kyowa Kirin, Meiji Seika Pharma, Minophagen, Nippon Shinyaku, Ono Pharmaceutical, Sanofi, and Takeda Pharmaceutical; and support for attending meetings and/or travel from Takeda Pharmaceutical. Hiroko Fukuda, Kyoko Minamino, Yukiyoshi Moriuchi, and Koichi Ohshima declare no conflicts of interest.
Supporting information
Supporting Figure 1: Additional endoscopic findings. (A) Endoscopic image showing the main lesion (arrowheads) and a separate, similar whitish lesion with slight elevation (arrows) in the lower thoracic esophagus. (B) Mid‐ to long‐distance narrow‐band image showing the two lesions.
Acknowledgments
The authors thank Alison Sherwin, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.
Data Availability Statement
The original data are available on a collaborative basis upon request to the corresponding author (Junya Makiyama).
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supporting Figure 1: Additional endoscopic findings. (A) Endoscopic image showing the main lesion (arrowheads) and a separate, similar whitish lesion with slight elevation (arrows) in the lower thoracic esophagus. (B) Mid‐ to long‐distance narrow‐band image showing the two lesions.
Data Availability Statement
The original data are available on a collaborative basis upon request to the corresponding author (Junya Makiyama).