Gastric Lymphoma

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Continuing Education Activity

Gastric lymphoma is a rare malignancy that comprises less than 5 % of all neoplasms in the stomach. However, the incidence in the united states is rising. Patients often present with non-specific symptoms that lead to misdiagnosis and delay in treatment. The majority of gastric lymphomas are associated with H. pylori, and treatment is tailored to eradicating this organism. To achieve optimal outcomes, practitioners need to be familiar with gastric lymphoma and be aggressive with diagnosis and management. This activity highlights some of the current diagnostic modalities and treatment options available.


  • Identify the etiology of gastric lymphoma medical conditions and emergencies.
  • Summarize the evaluation of gastric lymphoma.
  • Outline the management options available for gastric lymphoma.
  • Review some interprofessional team strategies that can result in better care coordination for patients presenting with gastric lymphoma.


Gastric lymphoma accounts for only 3% of gastric cancers but is the most common location for extranodal Non-Hodgkin Lymphomas. These indolent cancers are often composed of mucosa-associated lymphoid tissue (MALT) with heterogeneous B-cells located in the stomach or diffuse large B-cells (more often high grade). More than 90% of Gastric MALT Lymphomas are associated with Helicobacter pylori infections. For this reason, treatment of H. pylori remains a key factor in treating gastric lymphomas.[1][2][3][4]


Helicobacter pylori are one of the most common chronic infections, with an estimated 50% of the world’s population having been infected or previously infected by the bacteria. H. pylori are present in up to 90% of patients with gastric MALT Lymphoma. Untreated H. pylori lead to chronic inflammation and proliferation of T-cells and B-cells in the gastric mucosa. Gastric mucosa does not typically have lymphoid tissue but can develop mucosal-associated lymphoid tissue in response to longstanding inflammation. This aberrant tissue can lead to malignant transformation, commonly known as gastric MALT lymphoma. In most cases, the lymphoid tissue resolves with the eradication of H. pylori. Cases refractory to H. pylori eradication are more likely to contain a genetic mutation; the highest prevalence seen with t(11;18) (q21;q21).[5][1][6]


Gastric lymphoma is rare, but the incidence of the disease is increasing. It accounts for up to 40% of extranodal lymphomas but only 3% to 5% of gastric neoplasms. The risk of gastric lymphoma increases with advancing age. A significant increase in incidence occurs after 40, with a peak incidence in the sixth decade of life. Males are 2-3 times more likely to develop primary gastric lymphoma than females.[3][7][6]


Gastric lymphoma arises from the formation of aberrant lymphoid tissue in the stomach. In the vast majority of cases, antigen stimulation by H. pylori recruits B-cells and T-cells to the gastric mucosa giving way to chronic inflammation. Malignant transformation into a low-grade gastric MALT lymphoma happens in the minority of patients with chronic H. pylori gastritis. High-grade gastric MALT lymphomas commonly consist of monoclonal B-cells that progress independently of the presence of H. pylori. Diagnosing and treating low-grade gastric lymphomas is key to preventing progression to high-grade lymphomas that have higher rates of complications, lower rates of regression, lower disease-free survival, and lower overall survival.[1]


Gastric lymphomas can be classified histologically as marginal zone B-cell lymphomas of MALT type, diffuse large B-cell lymphomas, follicular lymphomas, mantle cell lymphomas, Burkitt’s lymphomas, T-cell lymphomas, and plasmacytomas. MALT lymphoma and large B-cell lymphomas make up nearly 90% of all gastric lymphomas. The histologic characteristics of MALT lymphoma include centrocyte-like cells, plasma cell infiltration, and destruction of gastric crypts defined as lymphoepithelial lesions. These centrocyte-like cells will express CD19, CD20, and CD79a but do not express CD5, CD10, CD23, and cyclin D1.[6]

History and Physical

Presenting symptoms for gastric lymphoma vary widely. Commonly patients present with abdominal pain, early satiety, nausea, vomiting, and indigestion. Patients can present with B symptoms (fever, night sweats, and weight loss), but these symptoms are less common. Patients can present with GI bleeding that can range from occult bleeding leading to iron deficiency anemia or acute blood loss presenting as hematemesis, hematochezia, or melena. Obstruction and perforation are rare presentations of gastric lymphoma. The physical exam is often benign but can include epigastric tenderness, a palpable mass, and lymphadenopathy.[3][8][7][9]


Gastric lymphoma is most commonly found in the gastric antrum, and the gold standard for diagnosis is upper endoscopy with biopsies, tissue analysis by trained pathologists, and immunohistochemistry. Endoscopically, gastric lymphoma can present as ulcers, heterogeneous masses, or a combination of ulcers and masses in multiple locations at various stages. Once diagnosed, a CT scan with IV and PO contrast of the chest, abdomen, and pelvis are obtained to assist with staging. Endoscopic ultrasound is often used to evaluate the depth of invasion, peri-gastric lymph node involvement, and staging of disease but is not required for diagnosis.  Diagnosing H. pylori is an important component when diagnosing gastric lymphomas as it is present in up to 90% of cases, and eradication is an important part of treatment. Non-invasive and invasive tests exist for H. pylori, and a patient should have two negative tests before considering them uninfected.

PET-CT scans have been used to localize regions for biopsy in certain scenarios but are not required for diagnosis.  Bone marrow biopsies are not required in primary gastric non-Hodgkin lymphomas. Complete blood counts with flow cytometry, renal function, liver function, protein electrophoresis, serum lactate dehydrogenase, Beta-2 microglobulin, hepatitis serologies, and HIV serology are the necessary labs in the initial workup of a patient diagnosed with gastric lymphoma.[1][10][11]

Treatment / Management

Once a gastric MALT lymphoma diagnosis is made, the patient should be treated with H. pylori eradication therapy according to current guidelines, the patient’s prior antibiotic exposure, and local antibiograms. Non-invasive testing for H. pylori should be performed to confirm eradication with either a urea breath test or stool antigen test 6 weeks after therapy is complete.  It is important to understand that even if a patient is confirmed H. pylori-negative with two different forms of testing before eradication therapy, they should still be treated with two weeks of antibiotics and proton pump inhibitors according to H. pylori treatment guidelines. Prior personal exposure to macrolide therapy imparts resistance to H. pylori, thus leading to reduced eradication rates with an antibiotic regimen containing a macrolide. Gastric MALT lymphomas have been shown to respond to H. pylori eradication therapy regardless of bacterial presence at the time of lymphoma diagnosis in >75% of cases. 

In patients with low-grade gastric MALT lymphomas (Laguna Stage I-IIE), an upper endoscopy should be performed 3 to 6 months after H. pylori eradication. During this endoscopy, the gastric mapping should be performed with a histologic evaluation of each specimen using Sydney protocol. Complete remission or complete histological response is determined if there is the total resolution of diffuse lymphoid infiltrates and lymphoepithelial lesions of the biopsy specimens on two consecutive endoscopies. Of note, evidence of histologic remission may take 1 to 14 months post-H. pylori eradication to become apparent.  If an experienced pathologist determines complete remission, complete histologic response, or probable minimal residual disease, the patient should undergo upper endoscopies with biopsies every 6 months for the first 2 years. After 2 years, the patient can be extended to one upper endoscopy with gastric mapping biopsies every 12 to 18 months.

If a patient has evidence of partial response or responding residual disease of low-grade gastric MALT lymphoma after H. pylori eradication therapy, the patient should have an upper endoscopy with gastric mapping biopsies every 3 to 6 months with an expected observation approach. If a patient has no change in low-grade gastric MALT lymphoma after H. pylori eradication therapy, they can be given the option to perform upper endoscopies every 3-6 months with gastric mapping biopsies with the intent of expected observation, or they can choose to be treated with localized radiation or chemotherapy and/or rituximab.

Patients with high-grade gastric MALT lymphoma (Laguna Stage IV) who are asymptomatic can choose expected observation or a more aggressive strategy pending patient preference.  Expected observation is performed with upper endoscopies and abdominal imaging (ultrasound or computed tomography) every 6 months after H. pylori eradication. H.pylori treatment alone may lead to remission of high-grade gastric MALT lymphoma in a minority of patients.

A patient with high-grade gastric MALT lymphoma who is symptomatic, has overt progression, bulky disease, or chooses a more aggressive approach can begin radiation, chemotherapy, and/or immunotherapy with rituximab, but only after H. pylori eradication therapy.

Surgery should be reserved for acute bleeding patients not amenable to endoscopic therapy, perforation, or obstruction.  Practitioners should inform patients that radiation remission rates are higher than chemotherapy and/or immunotherapy in gastric MALT lymphoma, with some studies reporting >95% complete histologic remission rates.  Immunotherapy with rituximab increases the risk of hepatitis B reactivation and should be discussed with patients before choosing treatment options. Screening for HIV, hepatitis B, and hepatitis C should be completed before starting rituximab.[1][12][6][13][5][14][15]

Differential Diagnosis

  • Peptic ulcer disease
  • Celiac disease
  • Symptomatic cholelithiasis
  • Pancreatitis
  • Marijuana hyperemesis syndrome
  • Gastritis
  • Gastroparesis
  • Inflammatory bowel disease
  • Pancreatic cancer
  • Gastroesophageal reflux disease
  • Diverticulitis

Surgical Oncology

Surgical resection of gastric lymphoma was the initial first-line treatment. It is now reserved for complications such as perforation, obstruction, or bleeding not amenable to endoscopic therapy. Surgery by an experienced surgical oncologist can be considered in progressive gastric lymphoma despite H. pylori eradication, chemotherapy/immunotherapy, and radiation if the patient defers an expected observation approach. The patient and physician should discuss the risks (as discussed in the Complications section) and the benefits of surgery.

Radiation Oncology

Radiation has been demonstrated to be the most effective treatment for gastric lymphomas refractory to H. pylori eradication. It is best suited for localized disease with its known side effects. Given the rarity of gastric lymphoma, a radiation oncologist experienced in gastric lymphomas should perform the desired treatment.


Staging any neoplastic disease is crucial for determining treatment options and prognosis.  Gastric lymphoma lacks a uniform staging system. TNM staging has proven to be ineffective in lymphomas.  As a result, the Ann Arbor classification system has historically been used for Hodgkin and Non-Hodgkin lymphomas. The Ann Arbor classification system lacks specific relevant features needed to stage extra-nodal gastric lymphomas  

The most commonly used staging system is the Lugano staging system which is one of the proposed modifications of Ann Arbor classification.  Lugano staging consists of Stage I, Stage II (1, 2, & E), and stage IV.  There is no stage three disease and correlates with many experts who believe gastric lymphomas should be categorized as low or high-grade lymphomas.  Stage I is defined by lymphoma confined to the gastrointestinal tract.  Stage II indicates gastrointestinal lymphoma that extends into the abdomen. Stage II1 indicates local nodal involvement, whereas Stage II2 indicates distant nodal involvement. Stage IIE is defined as an invasion of the serosa to involve adjacent organs or tissues. Stage IV is defined as disseminated extra-nodal involvement and/or the presence of supradiaphragmatic nodal involvement. 

The Paris staging system is occasionally used in addition to Lugano with a focus on depth of invasion into the gastrointestinal wall to delineate disease stage more accurately.[4][16]


Gastric Lymphomas are slow-growing indolent neoplasms that respond well to treatment, especially if caught early in the course of the disease. Low-grade gastric MALT lymphomas involving the mucosa and submucosal layers carry a favorable prognosis with up to 90% survival at 10 years. In the vast majority of cases, the low-grade disease can completely resolve with H. pylori eradication therapy alone and recurrence of disease can be influenced by re-infection with H. pylori. Deeper tissue involvement and the presence of chromosomal translocation (t(11;18)(q21;21)) can indicate an increased rate of progression to high-grade disease that does not resolve with H. pylori eradication therapy alone.

High-grade gastric MALT Lymphoma may eventually require chemotherapy, immunotherapy, and/or surgery despite having slow progression over time. MALT-IPI was developed to categorize patients with gastric MALT lymphoma into three prognostic groups: low risk, intermediate-risk, and high risk. The risk factors assessed are age greater than or equal to 70, elevated serum lactate dehydrogenase levels, and Ann Arbor Stage III or IV disease.

If no risk factors are present, the patient is considered low risk with a 5-year event-free survival rate approaching 70% and overall survival of 99%. Intermediate risk patients with one risk factor present carry a 5-year event-free survival rate of 56% and an overall survival rate of 93%. Patients with over 2 risk factors are believed to have higher rates of poor outcomes with a 5-year event-free survival rate of 29% and overall survival of 64%.[12][17][6][13][1]


Adverse events associated with gastric MALT Lymphoma increase as the disease progresses. Complications from the disease alone include gastrointestinal bleeding, perforation, and gastric outlet obstruction. Invasion into surrounding organs such as the hepatobiliary system and pancreas can lead to numerous complications, including biliary obstruction, infection, and pancreatitis.

Radiation always carries a risk of complications that increases with the dose given to include adhesions, scarring, pancreatitis, and various other complications arising from inflammation and scarring. Immunotherapy with Rituximab carries a risk of Hepatitis B reactivation, leading to acute liver failure and even death in extreme cases. Hepatitis B serology should be checked before initiating rituximab. Surgery complications include bleeding, gastric outlet obstruction, anastomotic leaks, adhesions, fistulas, and infection.

Deterrence and Patient Education

The patient should be educated on the slow progression of the disease and the options, which range from an expected observation approach to more aggressive options, including a combination of chemotherapy, immunotherapy, radiation, or surgery. Patients must be educated on the importance of compliance with H. pylori eradication therapy as this alone can lead to regression of the disease if taken correctly and prevention of progression to high-grade disease.

Enhancing Healthcare Team Outcomes

Research is limited, given the low incidence of gastric lymphoma. More clinical trials are needed to develop a uniform staging system and define the usefulness of various imaging techniques (especially endoscopic ultrasound) when staging gastric lymphoma. Education and incorporation of many specialties, including gastroenterology, radiology, hematology, oncology, and surgical oncology, are paramount in progressing the diagnosis and treatment of gastric MALT lymphoma. Personalized and targeted treatments appear to be the future in the management of gastric lymphomas.

Article Details

Article Author

Vincent Herlevic

Article Editor:

James D. Morris


12/28/2021 11:54:01 PM

PubMed Link:

Gastric Lymphoma



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