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Primary Gastric Lymphoma


Last updated: August 14, 2020
Years published: 1990, 1991, 1992, 1993, 1995, 1997, 2000, 2011, 2014, 2017, 2020


NORD gratefully acknowledges Join Y. Luh, MD, FACP, Clinical Associate Professor, and Charles R. Thomas, Jr., MD, Professor and Chair, Department of Radiation Medicine, OHSU Knight Cancer Institute, for assistance in the preparation of this report.

Disease Overview


Primary gastric lymphoma is a general term for a type of cancer that originates within the stomach. Approximately 90 percent of patients of primary gastric lymphoma are either mucosa-associated lymphoid tissue (MALT) gastric lymphoma or diffuse large B-cell lymphoma (DLBCL) of the stomach. MALT gastric lymphoma is often associated with infection with the Helicobacter pylori bacterium. Within the medical literature, controversy exists regarding the exact definition, classification and staging of primary gastric lymphoma.

The term lymphoma refers to cancer that arises in the lymphatic system. As part of the immune system, the lymphatic system helps protect the body against infection and disease, and has a network of tubes known as lymph vessels that drain a thin watery fluid known as lymph from different areas of the body into the bloodstream. Lymph collects in the tiny spaces between tissue cells and contains proteins, fats, and certain white blood cells known as lymphocytes. As lymph moves through the lymphatic system, it is filtered by a network of small structures known as lymph nodes that help to remove microorganisms (e.g., viruses, bacteria, etc.) and other waste (dead cells and their fragments) from the bloodstream.

Most types of lymphoma result from errors in the production of a type of white blood cell (lymphocyte) or transformation of a single lymphocyte into a malignant (cancerous) cell. Abnormal, uncontrolled growth of malignant lymphocytes leads to enlargement of a specific lymph node region or regions. Involvement of other lymphatic tissues, such as the spleen and bone marrow and spread to other body tissues and organs can lead to life-threatening complications. The specific symptoms (fever, night sweats, itchiness, etc.) and physical findings (weight loss, enlarged spleen, lumps over the neck or axilla, etc.) may vary from person to person depending upon the extent and region(s) of involvement.

Most cases of lymphoma arise in the lymph nodes. When lymphoma arises outside the lymph nodes, it is referred to as extranodal lymphoma. Primary gastric lymphoma is the most common form of extranodal lymphoma.

Most cases of primary gastric lymphoma are B-cell subtypes of non-Hodgkin lymphoma (NHL). NHL may be broadly classified into lymphomas that arise from abnormal B-lymphocytes (B-cell lymphoma) and those derived from abnormal T-lymphocytes (T-cell lymphoma).

The types of NHL may also be based upon certain characteristics of the cancer cells as seen under a microscope and how quickly they may tend to grow and spread. For example, NHL may be characterized as “low-grade” (or indolent), meaning it tends to grow slowly and result in few associated symptoms, or “intermediate-” to “high-grade” (aggressive) lymphomas, which typically grow rapidly, requiring prompt treatment. MALT gastric lymphoma is generally an indolent (slow growing) lymphoma; DLBCL of the stomach is generally a more aggressive lymphoma. Rarely, individuals may have both low and high grade lymphomas at the same time.

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  • non-Hodgkin gastric lymphoma
  • primary Hodgkin's lymphoma of the stomach
  • stomach lymphoma, non-Hodgkins type
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  • diffuse large B-cell lymphoma (DLBCL) of the stomach
  • mucosa-associated lymphoid tissue (MALT) gastric lymphoma
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Signs & Symptoms

The symptoms of primary gastric lymphoma are usually vague and nonspecific, seen in other conditions beside cancer. In many cases, there may be no noticeable physical findings upon diagnosis. Specific symptoms can be very different from one person to another. Abdominal pain or cramping is probably the most common, and may be one of the first symptoms noted.

Additional symptoms that may occur in individuals with primary gastric lymphoma include a feeling of stomach fullness after only eating a little food (early satiety), abdominal tenderness, nausea, vomiting, unintended weight loss, a general feeling of poor health (malaise), and indigestion. Bleeding from the stomach may occur in some individuals and can also be the first noticeable sign of primary gastric lymphoma. A mass large enough to be able to be felt when applying pressure to the stomach may also be present in some advanced cases.

Less frequently, weakness, fatigue, night sweats, jaundice (yellowing of the skin and the whites of the eyes), fever, and dysphagia (difficulty swallowing) may occur. Additional less common findings associated with primary gastric lymphoma include abnormal enlargement of the liver or spleen, obstruction of the gastrointestinal tract, and development of a hole or tear in the wall of the stomach (perforation).

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The exact cause of primary gastric lymphoma is unknown. However, a strong association between infection with Helicobacter pylori (H. pylori) and the development of MALT gastric lymphoma has been established. H. pylori is a bacterium that is found in the stomach and the upper portion of the intestines and is well known for causing ulcers.

In approximately 90 percent of cases, MALT gastric lymphoma is strongly associated with chronic H. pylori infection. MALT gastric lymphoma originally arises from certain white blood cells (lymphocytes) found within the lymphoid tissue of the stomach’s inner lining (mucous membranes or mucosa). This lymphoid tissue is not normally found in the stomach but develops as a result of chronic inflammation as occurs with chronic H. pylori infection.

Although H. pylori infection plays a role in the development of MALT gastric lymphoma, the infection is quite common in the general population. Yet only a very small number of individuals with this bacterium develop MALT gastric lymphoma. This indicates that other factors, such as a weak response to the infection by the body’s immune system, also play a role in the development of MALT gastric lymphoma.

Some individuals with MALT gastric lymphoma have chromosomal abnormalities within the tumor(s), specifically a translocation. A translocation means that a piece of one chromosome breaks off and attaches to another. These chromosomal abnormalities may be significant in terms of treatment or prognosis. For example, some affected individuals have a translocation involving chromosomes 11 and 18 (translocation t [11; 18]), which seems to be associated with poorer response to antibiotic therapy and the eradication of H. pylori infection.

Diffuse large B-cell lymphoma (DLBCL) of the stomach may arise spontaneously in individuals without a previous history of cancer, or it may occur from the transformation of an indolent MALT gastric lymphoma into the more aggressive DLBCL form. Some researchers have suggested that DLBCL of the stomach may also be associated with H. pylori infection. Some individuals with DLBCL of the stomach have been infected with the H. pylori bacterium, but some researchers believe that these cases are examples of long-standing MALT gastric lymphoma that has transformed into the more aggressive DLBCL of the stomach.

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Affected populations

Primary gastric lymphoma is estimated to affect approximately 1 in 100,000 people in the general population in Western countries. Several reports have noted that the incidence is increasing. Most cases of primary gastric lymphoma occur in individuals 50 years or older, with a peak incidence in the 60s and 70s. However, cases have been reported in children, adolescents, and young adults as well. Some reports suggest that men are affected more often than women. Primary gastric lymphoma has also been reported to occur more frequently in Caucasians than African-Americans.

As mentioned earlier, primary gastric lymphoma is the most common form of extranodal non-Hodgkin lymphoma (NHL), accounting for 30-40 percent of all extranodal sites. Primary gastric lymphoma accounts for 10-15 percent of all NHL cases. Although it is the most common extranodal site for NHL, primary gastric lymphoma is extremely rare, accounting for only 2-8 percent of all cases of stomach cancers.

Diffuse large B-cell lymphoma (DLBCL) and MALT lymphoma are the second and third most common subtypes of NHL (this is for all cases of these subtypes, not just those confined to the gastrointestinal tract).

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Primary gastric lymphoma is diagnosed based upon a thorough clinical evaluation, detection of certain symptoms and physical findings, a detailed patient history and a variety of specialized tests. Such testing is necessary to confirm the specific type (and subtype) of NHL present, to assess the nature and extent of the disease and to determine the most appropriate treatments.

For individuals with suspected gastric lymphoma as suggested by patient history and physical examination, various diagnostic tests may be recommended. These include blood tests, biopsies, bone marrow aspirates, and specialized imaging tests. For example, blood tests may include studies to evaluate the number and appearance of white blood cells, red blood cells, and platelets; tests to measure levels of the enzyme lactate dehydrogenase (LDH); and/or other studies. (High elevations of LDH may suggest that the lymphoma may have rapid progression, potentially requiring more intensive therapies.)

For individuals suspected of primary gastric lymphoma, a surgeon or gastroenterologist (a physician specializing in diseases of the digestive organs) will perform a procedure called an esophagogastroduodenoscopy (EGD), also called an upper GI (gastrointestinal) endoscopy. During an EGD, a light, flexible tube with a camera (endoscope) is inserted into the stomach or gastrointestinal tract to allow a physician to view the areas of abnormal tissue. An endoscope also allows a physician to perform a biopsy or biopsies (removal of a small sample of tissue or multiple samples for study under a microscope by a pathologist–a physician who specializes in diagnosing disease through the study of tissue, fluids and blood). The EGD and biopsy procedure may be conducted under local or whole body (general) anesthesia.

Microscopic analysis of affected tissue lets pathologists determine additional microscopic features that may be important in the malignancy’s classification, such as the size of malignant lymphocytes, appearance of the nucleus within a lymphoma cell, distribution or pattern of the abnormal cells, etc. In addition, specialized studies are conducted to help determine the malignancy’s specific cell type of origin. For example, gastric lymphoma cells–and the normal cells from which the malignancy develops–produce distinctive proteins (antigens) that may promote an antibody (immune) response (e.g., antigens such as CD20). They also may express certain antibodies on their outer surfaces (e.g., immunoglobulin M [IgM]). Thus, testing to identify such markers assists in determining the normal cells from which the malignancy derived, helping to distinguish primary gastric lymphoma from other types of lymphoma and aiding in diagnosis and treatment decisions.

Various specialized imaging procedures may also be recommended, such as standard x-ray imaging or computed tomography (CT) scanning. Specialized imaging procedures are generally used to help establish a diagnosis and to determine the extent of the disease. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of internal structures. For those with suspected or diagnosed NHL, CT scans may be taken of the neck, chest, abdominal, and/or pelvic regions to help detect enlargement of certain lymph nodes or spread of the malignancy to certain organs. Although abnormalities of the stomach mucosa are difficult to see on CT scans, such scans are useful in showing any extension or spread of the lymphoma to other parts of the body where they can be more easily seen on CT.

PET scans (positron emission tomography) are an important diagnostic exam for lymphoma. Cancer cells, like lymphoma, metabolize sugar more rapidly than normal cells. PET scans are a nuclear medicine imaging technology where radioactive glucose is injected into the patient and cancer cells take up this glucose more rapidly and in much higher quantities than normal cells, causing the cancer cells to “light-up” on the scan. PET scans are useful in showing to what extent the lymphoma has spread. They can also be used to measure a patient’s response to treatment. PET scans are often performed in conjunction with a CT scan, and when this is done, a separate CT scan can often be omitted. Unfortunately, PET scans can light up in parts of the body where there is infection or inflammation in the absence of cancer, resulting in a false positive scan. Although PET scans are commonly used to stage and follow patients with nodal NHL, they are only used in selected cases of gastric lymphomas getting radiation therapy, as PET images can help define the target for treatment.

MRI (magnetic resonance imaging) can be considered when CT scans and/or PET scans do not provide the needed information. Nevertheless, MRI is not considered a standard imaging study used in the staging, workup, and follow-up of gastric lymphomas.

When an individual is diagnosed with primary gastric lymphoma, the “stage” needs to be determined. Staging helps describe how far the disease has spread, characterize the potential disease course, and determine the right treatment. Some of the same diagnostic tests described above may be used in staging a primary gastric lymphoma (e.g., blood tests, CT scanning, PET scan, bone marrow aspiration and biopsy). Different staging systems have been proposed for primary gastric lymphoma. One of the more widely used staging systems used for primary gastric lymphoma was proposed during an international conference in Lugano, Switzerland, known as the Lugano Modification of Ann Arbor Staging System for Primary Nodal Lymphomas. Because this staging system applies to all lymphomas, there is a more specific Lugano Staging System for primary gastrointestinal lymphoma. The “E” subscript stands for extranodal, since gastric lymphomas tend to originate from the lining of the stomach instead of lymph nodes. It includes the following stages:

Stage IE – Lymphoma is confined to the gastrointestinal tract (single lesion or multiple non-contiguous lesions).
IE1 = mucosa, submucosa
IE2 = muscularis propria, serosa
Stage II – Lymphoma extends into the abdomen from the primary site within the gastrointestinal tract.
II1 = local nodal involvement
II2 = distant nodal involvement
Stage IIE – Penetration of serosa to involve adjacent organs or tissues.
Stage IV – Disseminated extranodal involvement or concomitant supra-diaphragmatic nodal involvement.

Note: Stage III involves lymphoma above and below the diaphragm and gastric lymphoma is always below the diaphragm, so Stage III does not exist for gastric lymphomas. If there is any involvement of lymph nodes above the diaphragm, the patient would be a Stage IV.

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Standard Therapies


The diagnosis and therapeutic management of primary gastric lymphoma requires the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer with chemotherapy and other drugs (medical oncologists), disorders of the gastrointestinal tract (gastroenterologists), disorders of the blood and blood-forming tissues (hematologists), or the diagnosis and treatment of cancer with radiation (radiation oncologists); oncology nurses; surgeons; dietitians; and/or other professionals.

Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size; specific lymphoma subtype; the presence or absence of certain symptoms; individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.

A wide variety of treatment options exist for individuals with primary gastric lymphoma including observation, antibiotic therapy, surgery, chemotherapy, and radiation therapy. These treatments may be used alone or in varied combinations.

Because MALT gastric lymphoma is slow-growing (indolent) form of lymphoma and because some individuals remain free of symptoms or disease progression for many years, physicians may recommend a watch and wait strategy. Watch and wait refers to when physicians follow a patient with a slow-growing cancer without giving treatment until progression of the disease occurs. This allows some people to avoid undergoing such therapies for many years and even decades in some cases, thus delaying the need to experience the side effects associated with treatment.

For individuals with early stage MALT gastric lymphoma confined to the stomach, antibiotics alone may be prescribed. Many studies have shown that curing MALT gastric lymphoma is possible with just antibiotics in many patients. The eradication of H. pylori with antibiotics is considered by many physicians to be a reasonable initial therapy for individuals with early stage MALT gastric lymphoma. Thorough follow up studies (e.g., blood tests and endoscopic biopsies) are required to confirm the eradication of the bacteria and to assess the response of lymphoma therapy. Continued follow up is also necessary because MALT gastric lymphoma can return if a person becomes re-infected with H. pylori.

On the other hand, anecdotal reports in the medical literature have described some cases of the more aggressive DLBCL of the stomach that have responded to antibiotic therapy including individuals who have gone into complete remission (all bloodwork, scans, and physical examination indicate the cancer is no longer present). Some researchers advocate that all individuals with DLBCL of the stomach and H. pylori infection should receive antibiotic therapy. Other researchers believe more research is necessary to determine whether antibiotic therapy is appropriate for treating this form of gastric lymphoma.

Some individuals with MALT gastric lymphoma may not respond to therapy with antibiotics. In these cases, radiation therapy to the stomach is often used. Radiation therapy is a treatment method that uses radiation to destroy cancer cells using beams generated from a linear accelerator (a large advanced X-ray machine) aimed at the tumor. A dose of 30 Gy or 3000 cGy is typically given, although a lower dose of 2400 cGy is also acceptable. In cases of advanced MALT lymphoma, and in cases of the more aggressive DLBCL of the stomach, chemotherapy is often used with or without radiation therapy. Higher doses of radiation (36 Gy or 3600 cGy) are used for cases of DLBCL of the stomach. Most people treated with radiation for MALT lymphoma are cured, with 87% of patients being alive after 10 years.


Despite the success of surgery in the past, surgery’s role in the treatment of primary gastric lymphoma is now only reserved for highly selected cases that do not respond to chemotherapy or radiation. The current standard of care for MALT gastric lymphoma is nonsurgical and includes antibiotics (if H. pylori positive) or locoregional radiation therapy to the stomach if there is persistent disease after antibiotics or if the patient does not have H. pylori infection. The current standard of care for gastric DLBCL is also nonsurgical and includes chemotherapy with or without subsequent locoregional radiation therapy depending on response to chemotherapy, or size of the initial tumor.

Chemotherapy is the use of several different drugs (given intravenously) alone or in combination to kill cancer cells. Chemotherapy is usually not needed for MALT gastric lymphoma, but biologic therapy with rituximab (discussed below) is used in patients who for one reason or another, cannot receive radiation therapy. Chemotherapy is used frequently in DLBCL of the stomach. The most common chemotherapeutic regimen used to treat individuals with DLBCL of the stomach is R-CHOP. The “R” stands for rituximab (Rituxan), a biological therapy (or immunotherapy), which has been highly successful in treating many types of lymphoma including DLBCL (although its role in treating of DLBCL of the stomach is less studied). Rituximab is a monoclonal antibody that is specifically directed against the CD20 antigen, which is a protein that may be found on the surface of certain lymphoma B-cells.

Monoclonal antibodies are produced by mature B-cells known as plasma cells; each plasma cell secretes a specific type of monoclonal antibody, which in turn acts against a specific antigen as part of an antibody-mediated immune response. Laboratories can now make large amounts of a specific monoclonal antibody that can be directed against a particular target, such as the CD20 antigen on lymphoma cells, often destroying the cell. Rituximab is an antibody that targets the CD20 antigen, and is often given with a standard chemotherapy regimen called “CHOP”. CHOP stands for: cyclophosphamide, hydroxydaunorubicin (doxorubicin or Adriamycin), Oncovin (vincristine) and prednisone.

The response to such treatments may vary widely. Nevertheless, Stage I-II DLBCL of the stomach are typically treated with 3 to 6 cycles of R-CHOP, followed by radiation therapy to the stomach to a dose of 3000 to 3600 cGy if there was a complete response to chemotherapy. If there was only a partial response, higher doses of radiation are often used. Stage III-IV DLBCL of the stomach is often treated with chemotherapy alone.

Some individuals may have insufficient response to standard chemotherapeutic regimens or may experience relapses, or the disease may become resistant (refractory) to treatment, potentially leading to life-threatening complications. Therefore, researchers are exploring the potential effectiveness of differing combinations of various chemotherapeutic drugs, high-dose chemotherapy regimens followed by stem cell/bone marrow transplantation, and/or other investigational therapies that may be warranted for selected individuals, possibly at the time of diagnosis, following certain standard therapies, and/or for those with refractory disease or relapse. They are also investigating appropriate ways in which to combine various therapies and to reduce potential side effects.

Other therapies for individuals with primary gastric lymphoma include symptomatic and supportive measures. These include but are not limited to medications to counteract nausea and vomiting, intravenous fluids to treat dehydration, pain medications, antacids to lower the risk of ulcers, stenting to open up any obstruction, and bone marrow stimulating drugs to reverse the low white blood cell counts (leukopenia) and red blood cell counts (anemia) caused by chemotherapy.

After completing treatment for primary gastric lymphoma, it is recommended that the patient get an EGD with biopsy in 3 to 6 months. If the biopsies show no evidence of lymphoma or H. pylori infection, then patients should follow up with their oncologist every 3 to 6 months for 5 years, then once a year. There is no set recommendation for how often a patient should get an EGD after the first post treatment EGD; however, if a patient begins experiencing unexplained nausea, abdominal pain, or fullness after eating small meals, then an EGD should be done.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com

For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/

Contact for authors:
Charles R. Thomas, Jr., MD
Professor & Chair
Department of Radiation Medicine
OHSU Knight Cancer Institute
Portland, Oregon
Tel: 503-494-8758
Fax: 503-346-0237
Email: thomasch@ohsu.edu

Join Y. Luh, MD, FACP
Clinical Associate Professor
Department of Radiation Medicine
OHSU Knight Cancer Institute
Department of Radiation Oncology
St. Joseph Hospital
2700 Dolbeer Street
Eureka, California, USA 95501
Tel.: 707.269.4229
Fax.: 707.269.3849

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(Newer editions are available, but the editions listed are the ones used for this update.)
Yamada T, Alpers DH, Kaplowitz N, Laine L, et al. Eds. Textbook for Gastroenterology. 4th ed. Lippincott Williams & Wilkins. Philadelphia, PA; 2003:1433-1434.

DeVita Jr VT, et al, eds. Cancer Principles and Practice of Oncology. 5th Ed. New York, NY: J.B. Lippincott Company; 1997:1025, 1185.

Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:941-46; 1065-66.

Juárez-Salcedo LM, Sokol L, Chavez JC, Dalia S. Primary gastric lymphoma, epidemiology, clinical diagnosis, and treatment. Cancer Control. 2018 Jan-Mar;25(1):1073274818778256. doi: 10.1177/1073274818778256.

Ohkubo Y, Saito Y, Ushijima H, et al. Radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma: long-term outcomes over 10 years. J Radiat Res. 2017 Jan 10. doi: 10.1093/jrr/rrw044. [Epub ahead of print]

Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68.

Psyrri A, Papageorgiou S, Economopoulos T. Primary extranodal lymphomas of the stomach: clinical presentation, diagnostic pitfalls and management. Ann Oncol. 2008;19:1992-1999.

Cavanna L, Pagani R, Seghini P, Zangrandi A, Paties C. High grade B-cell gastric lymphoma with complete pathologic remission after eradication of Helicobacter pylori infection: report of a case and review of the literature. World J Surg Oncol. 2008;6:35.

Tovorich M, Balint B, Jevtic M, et al. Primary gastric mucosa associated lymphoid tissue lymphoma: clinical data predicted treatment outcome. World J Gastroenterol. 2008;14:2388-2393.

Vrieling C, de Jong D, Boot H, de Boer JP, Wegman F, Aleman BM. Long-term results of stomach-conversing therapy in gastric MALT lymphoma. Radiother Oncol. 2008;87:405-11

Bacon CM, Du MQ, Dogan A. Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists. J Clin Path. 2007;60:351-372.

Houssain FS, Koak Y, Khan FH. Primary gastric Hodgkin’s lymphoma. World J Surg Oncol. 2007;5:119.

Ferrucci pF, Zucca E. Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years. Br J Haematol. 2006;136:521-538.

Cohen SM, Petryk M, Varma M, et al. Non-Hodgkin’s lymphoma of mucosa-associated lymphoid tissue. Oncologist. 2006;11:1100-1117.

Al-Akwaa A, Siddiqui N, Al-Mofleh IA. Primary gastric lymphoma. World J Gastroenterol. 2004;10:5-11.

Ibrahim EM, Ezzat AA, Raja MA, et al. Primary gastric non-Hodgkin’s lymphoma: clinical features, management, and prognosis of 185 patients with diffuse large B-cell lymphoma. Ann Oncol. 1999;10:1441-49.

Grethlein S. Mucosa-Associated Lymphoid Tissue. Medscape. Last Update January 17, 2019. Available at: https://emedicine.medscape.com/article/207891-overview  Accessed August 9, 2020.

National Comprehensive Cancer Network. Guidelines for Patients: Diffuse Large B-Cell Lymphomas (Version 3.2020). Available at: https://www.nccn.org/patients/guidelines/nhl-diffuse/index.html  Accessed August 9, 2020.

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