About Lymphoma > Types of Lymphoma > Marginal Zone Lymphomas

Last update: 04/20/2008

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Marginal Zone Lymphomas:  MALT, Nodal, Splenic subtypes

Marginal Zone Lymphomas are a related cancers of the lymphatic system - a complex system of lymph organs, including the bone marrow, thymus, spleen, and the lymph nodes.

What is lymphoma?  

Briefly, lymphomas result when damage or changes occurs to an immune cell (a lymphocyte) that alters the behavior of the cells.  The damage to DNA results in the abnormal production of proteins that prevents the cells from dying when they should, or causes sustained rapid cell division that produces more of its kind. The malignant cells then may accumulate to form tumors that may enlarge the lymph nodes or spread to other areas of the lymphatic system, such as the spleen or bone marrow. Lymphoma can also spread or first appear outside the lymphatic system - and is  called extranodal disease. 

The word "marginal zone" describes the cell type. B-cells arise from the bone marrow and mature or differentiate into many cell types that tend to migrate to different areas of the body in order to defend against pathogens (viruses, bacteria, etc.). 

"The marginal zone of the B follicle represents a well-defined compartment of the B-cell area, a distinct cellular composition from that of the follicle center (follicular b-cells), from which it also differs in its functional role in the immune response."

B-cell stage: Mature (peripheral) neoplasms

Incidence: Marginal Zone NHL is a relatively uncommon type of b-cell lymphoma, comprising approximately 2-4% of all cases. There are about 61,000 new cases of NHL diagnosed annually. Therefore we calculate that there are approximately 1,000 to 2,300 new cases of marginal zone NHL diagnosed annually. 

MZL/MALT are often infection-associated, antigen-driven: 
 
"H. pylori, C. jejuni, B. burgdorferi, C. psittaci, and hepatitis C virus (HCV), which have been associated with gastric lymphoma, immunoproliferative small intestinal disease, cutaneous lymphoma, ocular lymphoma, and spleen lymphoma, respectively." *

Source: Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation. Blood. 2006 Apr 15;107(8):3034-44. Epub 2006 Jan 5. Review. PMID: 16397126 | Related articles

Categories of marginal zone cells:  
"Extranodal Marginal Zone Cell Lymphoma (MZCL) of MALT-type share similar features with nodal and splenic MZCL regarding morphology  - cell appearance - and immunophenotype - cell expressions that indicate the maturation stage of the malignant cell. 

At the genetic level, recent cytogenetic studies have shown that t(11;18) is a recurring abnormality in extranodal MALT-type Marginal Zone Cell Lymphoma but has hitherto never been reported in nodal or splenic MZCL. Source: DoctorsDoctor

Common Subtypes of Marginal Zone Lymphomas:

There are three distinct forms (Harris et al, 1999) of marginal zone lymphomas:

Click the links above to go to the section on this page.

Monitoring MZL with PET?  See PET

Recommended Resources:

Non-gastric MZL

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"Non-gastric marginal zone B-cell lymphoma (NG-MZL) is a relatively uncommon indolent lymphoma.

From 1990 to 2005, a total of 247 patients with histologically confirmed
NG-MZL were analyzed.

Ann Arbor stage I/II disease was present in 78% (167 out of 215). 

One hundred eighty-six patients out of two hundred eight were categorized into the low/low-intermediate risk group (89%) according to International
Prognostic Index (IPI).

Eighty percent (172/215) were in low risk group according to Follicular
Lymphoma International Prognostic Index (FLIPI).

Complete and partial remissions (CR and PR) were achieved in 140 (92.7%) and 8 (5.3%) of the 151 stage I/II patients.

Especially, radiation containing treatment achieved 96% CR rate 
(108 out of 113).

In 38 patients with stage III/IV, CR and PR were achieved in 17 
(44.7%) and 11 (26.3%), respectively.

The estimated five-year overall survival (OS) and progression-free survival
(PFS) were 93.8% and 70.1%, respectively.

Although anthracycline-containing regimen could achieve higher CR rate, it
did not improve PFS.

Stage III/IV, low hemoglobin, poor performance status,
high/high-intermediate IPI, poor risk FLIPI, and nodal MZL were poor
prognostic factors for PFS.

NG-MZL is an indolent disease. FLIPI has strong power to predict the
prognosis of NG-MZL. 

Treatment

Also see: 

Treatment of non-follicular 
NHL - PDF

 
Questions for your doctor
  Patients Against Lymphoma
General, Treatment & Side Effects, and Tests


Treatment Overview

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Factors that determine treatment timing and approach:  

The characteristics of the lymphoma at diagnosis as determined by the pathology report, and it's actual clinical behavior, and other factors determine the type of treatment and the timing of treatment you and your doctor will consider. 

Resources & News

Clinical Trials

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Prognosis

Also see Prognostic Indicators

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more frequent in gastrointestinal than in non-gastrointestinal MALT lymphomas (22% vs 10%). 

The longer time to progression showed by Thieblemont et al. for gastrointestinal lymphomas has not been confirmed in our study. 

Although our data showed no significant differences in either DFS (disease free survival) or OS (overall survival) between the two groups of patients, the slight survival advantage for non-gastrointestinal MALT lymphomas could be explained by their local involvement and good performance status at diagnosis. 

It is possible that the single center nature of our study and the inclusion of only patients with unequivocal histologic criteria of MALT lymphoma, could have had some influence on the results." source: haematologica

Abstracts

Research News

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We moved this most common type of Marginal Zone Lymphoma 
to the MALT page

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"Splenic and nodal marginal zone lymphomas are typical low-grade lymphomas with an indolent course. A subset of patients, however, presents with more
aggressive disease and have a shorter survival. Clinical and biological prognostic factors identified in reported series are heterogeneous (varied). 

The role played by hepatitis C virus (HCV) in marginal zone lymphomas is not fully elucidated, but there is demonstration that eradication of HCV infection in splenic lymphoma with villous lymphocytes causes regression of the lymphoma. 

The optimal treatment has not yet been identified. Retrospective series, however, show that splenectomy is a good option if symptoms from the presence of spleen enlargement or cytopenias need to be treated. The utility of purine analogs and of anti-CD20 immunotherapy needs to be clarified in prospective trials."

1. Nodal monocytoid B-cell lymphoma (nodal marginal-zone B-cell lymphoma). Semin Hematol. 1999 Apr;36(2):128-38. Review. PMID: 10319381  PubMed

2. Technical: Marginal zone-related neoplasms of splenic and nodal origin.
   Haematologica. 2003 Jan;88(1):80-93. Review. PMID: 12551831 | Related articles 
   
   Full text  PDF 
   
   The marginal zone is an anatomically distinct B-cell compartment of lymphoid tissue with an abundant antigenic influx. Among marginal zone-derived lymphomas the WHO classification listed, in addition to extranodal marginal zone B-cell lymphoma of MALT type, two other marginal zone B-cell neoplasms: splenic marginal zone B-cell lymphoma (+/- villous lymphocytes) and nodal marginal zone B-cell lymphoma (+/- monocytoid B cells).

3. State-of-the-Art Therapeutics: Marginal-Zone Lymphoma - abstract only jco.ascopubs.org
   
   These data have determined unique approach among all other lymphoma subtypes: the possibility of treating a subset of patients with antibiotics alone as first line of treatment.
   
   Indeed, there is compelling evidence that histologic regressions can be achieved in most gastric MALT lymphomas by eradicating Helicobacter pylori infection. However, molecular follow-up studies showed the persistence of the malignant clone in half of the cases in histologic remission after antibiotic treatment and transient, either histologic or molecular, relapses have been reported, too. 
   
   Hence, a careful long-term follow-up is mandatory after antibiotic treatment. Radiotherapy, chemotherapy, anti-CD20 monoclonal antibodies are effective alternative therapies. The precise role of surgical resection should be redefined in view of the encouraging results of conservative approaches. 
   
   Differently from EMZL, both SMLZ and NMZL often present with disseminated disease at diagnosis. The therapeutic approach comprises splenectomy, for SMZL, and chemotherapy, but with no consensus about the best treatment. "
   
   

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TOPIC SEARCH: ASCO | PubMed | WEB

In "a retrospective study of the pathological features in 69 primary pulmonary non-Hodgkin's lymphomas which have previously been clinically reviewed. The tumors consisted of 61 (88%) low-grade and eight (12%) high-grade malignant lymphomas. Fifty-four of the low-grade malignant lymphomas were MALT lymphomas." [2]

Nearly half of the patients at diagnosis have no symptoms, and are identified incidentally on the basis of a radiological exams. Symptoms are usually non specific, such as cough, mild shortness of breath, chest pain and occasionally coughing of blood. [1]

"Clinical data suggest that limited surgery or non-aggressive chemotherapy can provide long-term survival in patients with such slowly developing neoplasms." [1]

"The role played by hepatitis C virus (HCV) in marginal zone lymphomas is not fully elucidated, but there is demonstration that eradication of HCV infection in splenic lymphoma with villous lymphocytes causes regression of the lymphoma. The optimal treatment has not yet been identified. Retrospective series, however, show that splenectomy is a good option if symptoms from the presence of spleen enlargement or cytopenias need to be treated." ⁵
 

1. About  radiology.uchc.edu | vera_b  

2. Primary pulmonary non-Hodgkin's lymphomas. Histopathology. 1995 Jun;26(6):529-37. PMID: 7665143  PubMed

3. Primary pulmonary lymphoma. Eur Respir J. 2002 Sep;20(3):750-62.
   PMID: 12358356  PubMed

4. Complete Pathologic Remission of BALT Lymphoma with Antibiotics, Case Report  ASCO 2002

5. Marginal zone-related neoplasms of splenic and nodal origin.
   Haematologica. 2003 Jan;88(1):80-93. Review. PMID: 12551831 | Related articles

6. Marginal Zone B-Cell Lymphoma of Bronchus-Associated Lymphoid Tissue (BALT): Imaging Findings in 21 Patients  chestjournal.org 
   
   Marginal zone B-cell lymphomas of BALT manifest diverse patterns of lung abnormality at CT, but single or multiple nodule(s) or area(s) of consolidation are the main patterns that occur in a majority (76%) of patients. Most lesions show heterogeneous but identifiable FDG uptake at PET.

7. Low-grade B-cell bronchial associated lymphoid tissue (BALT) lymphoma. Cancer Invest. 2002;20(7-8):1059-68. Review. PMID: 12449739 
   
   Low-grade B-cell bronchial associated lymphoid tissue (BALT) lymphoma is a distinct subgroup of non-Hodgkin's lymphoma. Chronic antigen stimulation, triggered by autoimmune process or persistent infection may precede the development of BALT lymphoma. The lymphoma cells originate from the marginal zone and by invading the bronchial epithelial tissue, give rise to the lymphoepithelial lesion. BALT lymphoma shares the morphologic, immunophenotypic, and cytogenetic characteristics of other mucosa associated lymphoid tissue lymphomas. 
   
   A majority of the patients are asymptomatic and pulmonary lesions are incidentally discovered on a routine chest radiograph. However, the clinical and radiographic features of BALT lymphoma are nonspecific. The disease is often localized at the time of diagnosis and responds favorably to local treatment, but the optimal management is not clearly defined. Overall, BALT lymphoma has a favorable prognosis and is associated with long-term survival. 

B-cell stage
Mature (peripheral) neoplasms

Also see: 

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A recently described primary Splenic lymphoproliferative disorder that mainly affects older individuals. 

Splenic Marginal Zone Lymphoma is an indolent (slow growing) b-cell lymphoma. It typically presents with an enlarged spleen (splenomegaly). "Splenic lymphomas present with a massive splenomegaly (enlarged spleen) sometimes with mesenteric lymph nodes or hepatic involvement, but without peripheral lymph nodes; bone marrow and blood are often involved." ² 

Treatment: Splenectomy is often indicated and can result in remissions. Treatment is similar to other indolent lymphomas - not typically initiated until the patient is symptomatic. 

 "Rituximab with or without chemotherapy was found to have major activity in patients with SMZL. These results may be associated with high levels of cellular CD20 antigen sites. Rituximab should be the treatment of choice, at least in older patients with SMZL who have comorbid diseases." [1]

About: 

1. Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 60 patients - full text  bloodjournal.org 

2. Splenic marginal zone lymphoma - Review article  bloodjournal.org 

3. Doctors-Doctors  doctorsdoctor.com 

Resources:

1. Outcomes in patients with splenic marginal zone lymphoma and marginal zone lymphoma treated with rituximab with or without chemotherapy or chemotherapy alone. Cancer. 2006 May 12; PMID: 16700034 | Related articles 
   
   "CONCLUSIONS: Rituximab with or without chemotherapy was found to have major activity in patients with SMZL. These results may be associated with high levels of cellular CD20 antigen sites. Rituximab should be the treatment of choice, at least in older patients with SMZL who have comorbid diseases."

2. Comparative study of marginal zone lymphoma involving bone marrow.
   Am J Clin Pathol. 2002 May;117(5):698-708. PMID: 12090417  PubMed

3. Splenic Marginal Zone Lymphoma Associated With Hepatitis B Virus Infection:
   A Case Report  ispub.com 

    

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TOPIC SEARCH: ASCO | PubMed | WEB

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a low-grade (slow growing) b-cell lymphoma that originates in the skin, with no evidence of extracutaneous disease.¹

"Cutaneous marginal zone B-cell lymphoma is a recently proposed entity and constitutes a cutaneous counterpart of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)." ²

MZCL appears to be a well recognizable entity, clinically, histologically and immunophenotypically. Although prognosis is generally good, the disease has potential for skin as well as extracutaneous recurrences. Large cell transformation and head and neck presentation may be associated with a worse prognosis.³

Primary cutaneous B-cell lymphomas have been associated with Borrelia burgdorferi, the spirochete responsible for Lyme disease. ⁴  This association warrants discussion of antibiotics as initial treatment.  See Related PubMed articles

1. Marginal Zone Lymphomas doctorsdoctor.com 

2. Primary cutaneous marginal zone B-cell lymphoma: a molecular and clinicopathologic study of 24 asian cases.
   Am J Surg Pathol. 2003 Aug;27(8):1061-9. PMID: 12883238

3. Primary cutaneous marginal zone B-cell lymphoma: a clinical, histopathological, immunophenotypic and molecular genetic study of 22 cases. Br J Dermatol. 2002 Dec;147(6):1147-58. PMID: 12452864

4. Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin. Hum Pathol. 2000 Feb;31(2):263-8. PMID: 10685647

5. Primary cutaneous marginal zone B-cell lymphoma. Am J Clin Pathol. 2006 Jun;125 Suppl:S38-49. PMID: 16830956