About Lymphoma | Advocacy | Art | CAM | Clinical trials | Doctors - Experts - Centers | Guidelines at Diagnosis | News
Risk Factors | Side Effects | Statistics | Support | Symptoms | Tests | Treatments | Types of Lymphoma

Search Site   |  How to Help!

Patients Against Lymphoma

 

Types of Lymphoma > Marginal Zone Lymphoma

Last update: 05/20/2014

TOPICS: 
Overview |
Monitoring non-gastric MZL | Treatment | Clinical Trials | Prognosis |
Resources & Research News |
Infection-associations

Common Types of Marginal Zone Lymphoma: 
     
MALT 
and other extranodal types: BALT | Cutaneous | Splenic

Less common types of MZL:

bullet

Nodal

bullet

Primary thyroid mucosa-associated lymphoid tissue lymphoma ncbi.nlm.nih.gov | Related reports

bullet

Parotid Gland Marginal Zone Lymphoma

TOPIC SEARCH: PubMed: Diagnosis | Review | Therapies | Prognosis

ABOUT
Lymphomas
Lymphoma Simplified

Overview of genes and cancer

Lymphoma is a blood cell cancer

About Lymphoma - general

Characteristics of NHL:
  Cell type | Histology | Grading | Staging

 Ann Arbor Staging 
  Extranodal notations 

Host/tumor
interactions

Lymphatic System

Risk Factors

Statistics
 
Staging
 
Symptoms

 Guidelines at diagnosis 

Treatment Decisions
 

When to treat?
 

Watch & Wait

  
Return to top

Marginal Zone Lymphomas

MALT | Pulmonary (BALT) | Splenic | Cutaneous (skin)  Nodal

Lymphoma is a blood cell cancer affecting lymphocytes - immune cells that normally protect our health by fighting infection.  Sometimes these specialized blood cells develop defects (mutations) that cause them to divide or persist longer than they should - forming tumors. The malignant lymphocytes may be t-cells (uncommonly) or b-cells.  One important role of normal b-cell lymphocytes is to make antibodies to fight infection.  See also Lymphoma Simplified 

Marginal Zone lymphoma (MZL) arises from defective b-cell lymphocytes. B-cells arise from the bone marrow and mature (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 word "marginal zone" describes the specific type of b-cell, but also the compartment of the body these cells defend.  

"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."

Natural History:

Marginal Zone Lymphoma (MZL) usually has a favorable and indolent (slow growing) course - similar to the most common indolent b-cell lymphoma called follicular lymphoma.  Transformation to aggressive lymphoma seems to be less common than for follicular lymphoma. 

A good many types of MZL are associated with infection that may cause the defective b-cells to persist and divide.  For this reason, treatment of the underlying infection can be the first line of therapy, such as treating MALT (gastric MZL) when there is an active h-pylori infection. 

See also Antibiotics for Lymphoma  and Infection-associations below.

Since MZL is relatively uncommon, new treatments for this condition are not often studied rigorously because of the challenge of enrolling a sufficient number of patients in well-controlled clinical trials.  For this reason, treatment of advanced stage MZL is guided by practice for indolent follicular lymphoma.

See also Natural History of Follicular Lymphoma

There is usually plenty of time after initial diagnosis to seek an expert second opinion on when to treat and with which approach.  We urge you to consult experts with medical training, experience, and first-hand information about your case ... and not to rely on Internet information.

The range of treatment or management options may include: 

bullet

Antibiotic therapy for infection-associated MZL
(time to best response may be slow - 12 months or more)

bullet

Radiotherapy - to treat localized MZL or judicious use to relieve symptoms - palliative care

bullet

Watchful waiting - treating conservatively as needed when symptoms or steady progression occurs

bullet

Rituxan therapy perhaps when there is a need to treat but also ample time to wait for a response

bullet

Rituxan with chemotherapy (such as Rituxan with Bendamustine or with CHOP) to treat with intent to achieve a durable remission.

bullet

Rituxan maintenance might also be considered after R-chemo

bullet

Radioimmunotherapy such as Zevalin

bullet

Clinical trials for targeted agents developed for b-cell lymphoma (many)

bullet

High dose chemotherapy with stem cell rescue for high risk MZL in select cases.

Localized MZL (not yet spread beyond the area of presentation) can be treated with curative intent - sometimes with radiotherapy.

For advanced (stage III/IV) MZL the goal of therapy is generally not to cure because it has not been demonstrated that aggressive standard therapies can achieve this goal at this time. 

See for our perspective on Goals of Therapy and
Curative Potential - preamble on when to consider trials

NOTE:  The above are impressions from the literature written by a patient advocate.  We will review with our scientific advisors and revise if needed very soon.  (3/20/2014 Karl)

In the News

bullet
Study of interest:
Testing Ibrutinib for Relapsed/Refractory Marginal Zone Lymphoma - ClinicalTrials.gov http://1.usa.gov/1863kvn
 
bullet
ASCO 2013: Comparative outcomes of splenectomy and rituximab-based chemotherapy in elderly patients with splenic marginal zone lymphoma.
bullet
MZL ASH 2012 abstracts
 

Recommended Expert Overview:

bullet
Hematology, 2012 Zinzani:
The many faces of marginal zone lymphoma http://bit.ly/1iGgRlc
bullet
Brad Kahl and David Yang
Marginal Zone Lymphomas: Management of Nodal, Splenic, and MALT NHL
asheducationbook

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. 

Marginal Zone Lymphomas are
Infection-associated, may be antigen-driven: 

The list of microbial species associated with MZL now comprises at least 6 distinct members:

bullet
H. pylori (gastric MALT)
 
A very high prevalence (up to 90% of cases) of Hp infection was reported in gastric MALT lymphoma.
bullet
Helicobacter heilmannii (immunoproliferative small intestinal disease)
bullet
Hepatitis C Virus (Nodal MZL)
bullet
Campylobacter  jejuni (cutaneous MALT)
bullet
B. burgdorferi from tick bite (cutaneous MALT - also Mantle Cell lymphoma)
bullet
C. psittaci from birds (orbital MALT)
Sources :
bullet
Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation. Blood. 2006 Review. PMID: 16397126 | Related articles 
bullet
Hematology, 2012 Zinzani:
The many faces of marginal zone lymphoma http://bit.ly/1iGgRlc
bullet Roggero E, Zucca E, Mainetti C, et al.
Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin.
 Hum Pathol. 2000;31:263–268. [PubMed]
 
bullet Clinical Trials and Observations: Borrelia infection and risk of non-Hodgkin lymphoma http://1.usa.gov/1eViXJf

Reports and Papers

bullet

Mediterr J Hematol Infect Dis. 2010:

Hepatitis C Virus Infection and Lymphoma http://1.usa.gov/neu1Kz  

snip:  

"If HCV infection has been inferred to be a factor in the development of NHL on the basis of case-control epidemiological studies as previously discussed, strong line of evidence also arose from response of so called HCV-associated lymphoma to antiviral therapy.

Of the 9 IFN-treated patients, 7 achieved a complete hematological remission, defined by the absence of abnormal lymphocytosis and the resolution of the splenomegaly, after HCV RNA load became undetectable. The remaining 2 patients experienced a partial or a complete response after addition of ribavirin and the loss of detectable HCV RNA. Conversely, none of 6 similarly treated HCV-negative SLVL patients responded to therapy thereby suggesting that the observed response rate was not due to the effect of interferon itself.

__________________
 

bullet
Hepatitis C in Hematological Patients http://1.usa.gov/oQExvz

Abstract:  There is no consensus guideline concerning the management of chronic hepatitis C patients during chemotherapy, and immunosuppression. However, there are some suggestions in literature that hepatitis C viral load increases during chemotherapy and there is a risk of rebound immunity against hepatitis C after discontinuation of immunosuppression with a consequent liver injury.

A close monitoring of liver function of these patients is prudent during treatment of haematological malignancy. Antiviral treatment is deferred after the completion of chemotherapy and recovery of patients' immunity to minimize the toxicity of treatment. A combination of pegylated interferon and ribavirin is the standard therapy in hepatitis C infected haematological patients.
bullet
Cancer: Prognostic value of the Follicular Lymphoma International Prognostic Index (FLIPI) score in marginal zone lymphoma: An analysis of clinical presentation and outcome in 144 patients.  with comments.
bullet
ASCO 2012 Marginal Zone Lymphoma abstracts

Also see abstracts for follicular lymphoma
bullet
MALT - MedWire:
‘Excellent’ outcomes after H. pylori eradication for gastric MALT
bullet
MALT - Alimentary Pharmacology and Therapeutics:
Common misconceptions in the management of H. pylori-associated gastric MALT
bullet
Marginal Zone - Annals of Hematology:
Phase II trial of rituximab plus CVP combination chemotherapy for advanced stage marginal zone lymphoma as a first-line therapy
 

Categories of marginal zone lymphomas:  

"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

Subtypes:

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

bullet

Extranodal
bullet

MALT (gastric)

bullet

BALT (lung)

bullet

Cutaneous (skin)

bullet

Splenic (spleen)

bullet

Uncommon subtypes:
bullet

Nodal (Monocytoid B-cell Lymphoma) 

bullet

Primary thyroid mucosa-associated lymphoid tissue lymphoma;
a clinicopathological study of seven cases ncbi.nlm.nih.gov | Related reports

bullet

Parotid Gland Marginal Zone Lymphoma
 

Return to top


Recommended Resources:

bullet
Non-Hodgkins Lymphomas 
 
Clinical Practice Guidelines in Oncology – v.1.2006  nccn.org professionals pdf (requires free subscription)
bullet
Technical: Nodal Marginal Zone Lymphoma - Differential Diagnosis: surgpathcriteria.stanford.edu/
bullet
Marginal Zone  NHL, overview - DoctorsDoctor | infobiogen 
bullet
Lymphomas outside the lymphatic system 

Extranodal Lymphomas
bullet
Overview
bullet
Cutaneous
bullet
Hepatic
bullet
Conjunctival/Ocular/Orbital
bullet
Osteo
bullet
Oral 

Return to top

Non-gastric MZL

Return to top

 

Monitoring Non-gastric Marginal Zone Lymphomas

Workup for Non-Gastric MALT
(adapted from NCCN Guidelines 2010)

bullet

Staging tests:
 
bullet

CT of Chest/abdominal/pelvic with contrast of diagnostic quality

bullet

Useful in select cases:
 
bullet

Endoscopy with multiple biopsies of anatomical sites

bullet

Bone marrow biopsy + aspirate (if multifocal disease)

bullet

MRI
 

bullet

Physical exam
 
bullet

Performance status

bullet

B symptoms (patient reported)
 

bullet

Labs and tests:
 
bullet

CBC, differential, platelets,

bullet

LDH

bullet

Comprehensive metabolic panel

bullet

Hepatitis B test (if Rituxan considered)

bullet

Useful in select cases:
 
bullet

Hepatitis C test
 

bullet

Treatment, age and gender specific:
 
bullet

MUGA scan / echocardiogram" 
(prior to anthracycline-based therapy)

bullet

Discuss fertility issues

bullet

Pregnancy testing in women of child-bearing age if chemo is planned
 

Related abstract:
bullet
Nongastric marginal zone B-cell lymphoma: Analysis of 247 cases.
Am J Hematol. 2007 Jan 31;  PMID: 17266060  
"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 (by cell type) 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. 

 

Return to top

 

Monitoring MZL with PET? 

bullet
See PET
Treatment
Also see: 

Treatment of non-follicular 
NHL - PDF

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

Treatment Overview
Return to top

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. 

bullet
See Factors that determine treatment timing and approach
bullet
See Flow chart for frontline indolent NHL
bullet
Your age and treatment priorities

Return to top


Resources & News

bullet
NEW Non-gastric Marginal Zone B-cell Lymphoma in Korea: Clinical Features, Treatment, and Prognostic Factors  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932933/
bullet
Marginal zone lymphomas - Factors that affect outcome interscience.wiley

Factors analyzed included age; gender; presence of B symptoms; performance score; clinical stage; serum 2-microglobulin, lactate dehydrogenase, albumin, and hemoglobin levels; and presence of autoimmune disorder.
bullet
Ongoing monoclonal B-cell proliferation is not common in gastric B-cell lymphoma after combined radiochemotherapy. J Clin Oncol. 2004 Aug 1;22(15):3039-45  PMID: 15284253
bullet
Autologous bone marrow transplantation for marginal zone non-Hodgkin's lymphoma. Leuk Lymphoma. 2004 Feb;45(2):315-20  PMID: 15101717 | Related abstracts
bullet
H-Pylori:  tests for and treatment of for MALT  PAL
bullet
Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood. 2003 Jul 3 PMID: 12842999  PubMed 
bullet
Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with cladribine: a phase II study. J Clin Oncol. 2002 Sep 15;20(18):3872-7. PMID: 12228207  PubMed
bullet
The primary gastric lymphoma: therapeutic strategies  Romeo Giuli MD
bullet
Conservative treatment of primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue: predictive factors of response and outcome. Am J Gastroenterol. 2002 Feb;97(2):292-7. PMID: 11866264   PubMed
bullet
Clinical trials

Return to top

Clinical Trials
Return to top

Clinical Trials

bullet
Find trials in the ClinicalTrials.gov registry

by type of lymphoma AND treatment status

Return to top

Prognosis

Also see Prognostic Indicators

Return to top

Prognosis

"Few studies have investigated the relation between the location of MALT lymphomas and their prognosis. In contrast to the results referred by Thieblemont et al.,7 we found that the tendency to progress or relapse seemed to be:

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

bullet
Splenic marginal zone lymphoma: a prognostic model for clinical use.
Blood. 2006 Feb 21; PMID: 16493005
bullet
[1125] Gene Expression Profiling Analysis in Splenic Marginal Zone Lymphoma Allows To Predict Survival and Histological Transformation. Session Type: Poster Session 279-I ASH 2004
bullet
Treatment outcome of mucosa-associated lymphoid tissue/marginal zone non-Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys. 2002 Mar 15;52(4):1058-66. PMID: 11958902  PubMed
bullet
Predictive value of endoscopic ultrasonography for regression of gastric low grade and high grade MALT lymphomas after eradication of Helicobacter pylori. Gut. 2001 Apr;48(4):454-60. PMID: 11247887  PubMed
bullet
Immunological and molecular analysis of B lymphocytes in low-grade MALT lymphoma of the stomach. Are there any useful markers for predicting outcome after Helicobacter pylori eradication? J Gastroenterol. 2002;37(6):428-33. PMID: 12108676  PubMed
bullet
Comparative study of marginal zone lymphoma involving bone marrow. Am J Clin Pathol. 2002 May;117(5):698-708. PMID: 12090417  PubMed

Return to top

Research News
Return to top

Research News

bullet
Nongastric marginal zone B-cell lymphoma: Analysis of 247 cases.
Am J Hematol. 2007 Jan 31;  PMID: 17266060  

Nongastric 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. Am. J. Hematol., 2007. (c) 2007 Wiley-Liss, Inc.

PMID: 17266060

bullet
Rituxan® Effective in Treatment of Splenic Marginal Zone Lymphoma and Marginal Zone Lymphoma   cancerconsultants.com  

" A complete or partial disappearance of detectable cancer was experienced by 88% of patients treated with Rituxan alone, 83% of patients treated with Rituxan and chemotherapy, and 55% of patients treated with chemotherapy alone.  The proportion of patients who survived for three years or longer was 95% among patients treated with Rituxan alone, 100% among patients treated with Rituxan and chemotherapy, and 55% among patients treated with chemotherapy alone."
bullet
Marginal Zone Lymphomas & Hepatitis C: Splenic and nodal marginal zone lymphomas are indolent disorders at high hepatitis C virus seroprevalence with distinct presenting features but similar morphologic and phenotypic profiles. Cancer. 2004 Jan 1; 100(1): 107-15. PMID: 14692030 | Related articles
bullet
IELSG phase II study of rituximab in MALT lymphoma: final results Year: 2002 Abstract No: 1067  
bullet
Stage I and II MALT lymphoma: results of treatment with radiotherapy. Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1258-64. PMID: 11483337  PubMed
bullet
Mucosa-associated lymphoid tissue lymphoma with initial supradiaphragmatic presentation: natural history and patterns of disease progression. Int J Radiat Oncol Biol Phys. 2000 Sep 1;48(2):399-403. PMID: 10974453  PubMed
bullet
Molecular follow-up in gastric mucosa-associated lymphoid tissue lymphomas: early analysis of the LY03 cooperative trial. Blood. 2002 Apr 1;99(7):2541-4. PMID: 11895791  PubMed
bullet
Of interest to pts with MALT: Randomized trial of endoscopy with testing for Helicobacter pylori compared with non-invasive H pylori testing alone in the management of dyspepsia  BMJ 2002;324:999 (27 April)
bullet
The Modified International Prognostic Index Can Predict The Outcome of Localized Primary Intestinal Lymphoma of Both Extranodal Marginal Zone B-Cell and Diffuse Larege B-Cell Histologies  International Extranodal Lymphoma Study Group (IELSG) British Journal of Haematology, 2002, 118, 218–228   PDF | PDF Help

Return to top


Subtype of Marginal Zone Lymphomas

MALT

Return to top

 

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

Nodal  (Monocytoid B-cell Lymphoma)

 
Return to top

 

Michiel van den Brand and J. Han J.M. van Krieken write:

"There is currently no consensus on how to treat NMZL patients. Usually, guidelines for follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma are adopted.

Different studies have reported different (combinations of) treatments, including watchful waiting, surgery, radiotherapy, different chemotherapeutic regimens, rituximab, and autologous stem cell transplantation. However, no optimal treatment strategy can be deduced from these studies. Complete response is achieved in 55–74% of patients.

".... Nodal marginal zone lymphoma remains an enigmatic entity with accompanying difficulties in diagnosis and a lack of knowledge of prognosis and treatment. Because of its rarity, it is hard to obtain large study groups. Also, because NMZL is frequently a diagnosis of exclusion, the series that have been studied might contain a somewhat heterogeneous group of low-grade B-cell lymphomas. Nevertheless, progress is being made; recent studies have identified positive markers for MZL (i.e. MNDA and IRTA1), and gene expression studies have identified a specific gene expression profile that separates NMZL from other lymphoma types. 

Source: 
Haematologica, 2013: Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review http://1.usa.gov/1kDQVXp
 

Workup for Nodal Marginal Zone
(adapted from NCCN Guidelines 2010)

bullet

Staging tests:
 
bullet

CT of Chest/abdominal/pelvic with contrast of diagnostic quality

bullet

Bone marrow biopsy + aspirate

bullet

Evaluation for extranodal primary sites:
 
Neck nodes: ocular, parotid, thyroid, salivary
Axillary nodes: lung, breast, skin
Mediastinal/hilar nodes: lung
Abdominal nodes: splenic and GI
Inguinal/iliac nodes: GI and skin

bullet

Useful in select cases:
 
bullet

Additional imaging as indicated by exam and reports

bullet

Endoscopy with multiple biopsies of anatomical sites
 

bullet

Physical exam
 
bullet

Performance status

bullet

B symptoms (patient reported)
 

bullet

Labs and tests:
 
bullet

CBC, differential, platelets,

bullet

LDH

bullet

Comprehensive metabolic panel

bullet

Hepatitis B test (if Rituxan considered)

bullet

Useful in select cases:
 
bullet

Hepatitis C test
 

bullet

Treatment, age and gender specific:
 
bullet

MUGA scan / echocardiogram" 
(prior to anthracycline-based therapy)

bullet

Discuss fertility issues

bullet

Pregnancy testing in women of child-bearing age if chemo is planned

Return to top

Resources

  1. Haematologica, 2013: Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review http://1.usa.gov/1kDQVXp

    Nodal marginal zone lymphoma remains an enigmatic entity with accompanying difficulties in diagnosis and a lack of knowledge of prognosis and treatment. Because of its rarity, it is hard to obtain large study groups. Also, because NMZL is frequently a diagnosis of exclusion, the series that have been studied might contain a somewhat heterogeneous group of low-grade B-cell lymphomas. Nevertheless, progress is being made; recent studies have identified positive markers for MZL (i.e. MNDA and IRTA1), and gene expression studies have identified a specific gene expression profile that separates NMZL from other lymphoma types.
  2. * JCO, 2005: State-of-the-Art Therapeutics: Marginal-Zone Lymphoma http://bit.ly/1g7MODo

    * JCO 2005: Role of Anti-Hepatitis C Virus (HCV) Treatment in HCV-Related, Low-Grade, B-Cell, Non-Hodgkin's Lymphoma: A Multicenter Italian Experience http://bit.ly/1nBEK1W

    * From jstage, Case report: Lacrimal Gland Marginal Zone Lymphoma: Regression
    after Treatment of Chronic Hepatitis C Virus Infection:
    Case Report and Review of the Literature http://bit.ly/1mfWNsV 
     
  3. Nodal monocytoid B-cell lymphoma (nodal marginal-zone B-cell lymphoma). Semin Hematol. 1999 Apr;36(2):128-38. Review. PMID: 10319381  PubMed
  4. Technical: 

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

    "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).
  5. 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. "
  6. 1990: Monocytoid B cell lymphoma: clinical and prognostic features of 21 patients http://www.ncbi.nlm.nih.gov/pmc/articles/PMC502639/

    The prognosis of MBCL was comparable with that of other low grade malignant lymphomas.
  7. Nodal Marginal Zone Lymphoma - Differential Diagnosis: surgpathcriteria.stanford.edu/

Return to top

Pulmonary (Lung) MALT Lymphoma

An Extranodal type of Marginal Zone Lymphoma
affecting
Bronchus-Associated Lymphoid Tissue (BALT)

 
Return to top

 

TOPIC SEARCH: PubMed  

Diagnosis:

As of this writing, there is a need for less invasive procedures to diagnose lesions that present in the lung .... which may be obtained by 

bullet video-assisted thoracoscopic (VATS) mayoclinic.org
bullet open thoracotomy nlm.nih.gov
bullet ultrasound-guided percutaneous biopsy  ncbi.nlm.nih.gov

Source

A favorable prognosis:

Most patients diagnosed with BALT are without symptoms and pulmonary lesions are incidentally discovered on a routine chest radiograph, which cannot be distinguished from other conditions by imaging features.

"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."   6

Treatment:

"The optimal management of BALT lymphoma with regard to surgery, chemotherapy, and radiation therapy alone or in combination, as well as abstention from therapy, has yet to be clearly determined.

From the perspective of MZL, localized PMZL, which is limited to one side of the lung, may be a marker of favorable response to local radiation or operation [9, 11, 14].

Additionally, advanced or disseminated P-MZL, involving bilateral lung or extra-pulmonary sites, could be controlled via chemotherapy. However, in the lung, even though the lesions were localized, radiation and surgical excision of segments or lobes should be carefully considered due to surgical complications, reductions in organ function, and a favorable clinical course of MZL itself.

In our series, we noted no difference between chemotherapy and operation in TTP and OS. This was the case even in the patients with single-lobe or unilateral P-MZL. Thus, in patients for whom surgery is not necessary for diagnosis, the operation might not be the first choice of PMZL treatment to preserve lung function and avoid the risks of surgery like any other primary pulmonary NHL [15, 16].

In another study, watchful vigilance until patients developed symptoms made no difference in terms of the efficacy of TTP treatment [17]. "Watchful waiting" might constitute another treatment option for asymptomatic patients. In order to assess the efficacy of this approach, a prospective multi-center randomized study will be necessary." ncbi.nlm.nih.gov
 

  1. Primary pulmonary non-Hodgkin's lymphomas.
    Histopathology. 1995 Jun;26(6):529-37. PMID: 7665143  PubMed
  2. Primary pulmonary lymphoma. Eur Respir J. 2002 Sep;20(3):750-62.
    PMID: 12358356  PubMed  Full text
  3. Complete Pathologic Remission of BALT Lymphoma with Antibiotics,
    Case Report  ASCO 2002
  4. Marginal zone-related neoplasms of splenic and nodal origin.
    Haematologica. 2003 Jan;88(1):80-93. Review. PMID: 12551831 | Related articles


    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. 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.
  6. 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. 
  7. Pulmonary marginal zone B-cell lymphoma of MALT type,"
    Ann Hematol (2010), p. 568 springerlink.com - full text pdf
     
  8. Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease
    http://www.ncbi.nlm.nih.gov/pubmed/15177490
     
  9. A patient with endobronchial BALT lymphoma successfully treated with radiotherapy http://www.ncbi.nlm.nih.gov/pubmed/17616383
     
  10. Bronchus-associated lymphoid tissue lymphomas
    http://www.ncbi.nlm.nih.gov/pubmed/20016430

Return to top

Splenic Marginal Zone Lymphoma (SMZL)

SMZL

B-cell stage
Mature (peripheral) neoplasms

Also see: Splenic Lymphoma with Villous Lymphocytes

 
Return to top

TOPIC SEARCH: 
PubMed  Diagnosis | Review | Therapies | Prognosis | Other

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."  

"Many cases show a protracted uncomplicated evolution, a good response to splenectomy or chemotherapy, or even an unmodified clinical picture in the absence of any kind of treatment. " 2

"Splenectomy will rapidly improve performance status and correct anemia, thrombocytopenia, and neutropenia within 6 months of the procedure.[19] This improvement is maintained for years, with a median period of freedom from treatment of 8 years, even if bone marrow and blood lymphocytosis persist, suggesting a partial response. Adjuvant chemotherapy following splenectomy provides an increased remission rate without modifying relapse-free and overall survival." 6

Antiviral therapy can lead to clearance of HCV RNA in 75% of patients and to concomitant clinical remission in SMZL associated with active HCV infection. 6

In the News

bullet
ASH Paper:
Outcomes In Splenic Marginal Zone Lymphoma: Analysis Of 108 Patients Treated In British Columbia http://bit.ly/1h7ozoK
bullet
Leuk Lymphoma 2013:
Treatment of splenic marginal zone lymphoma: should splenectomy be abandoned? http://1.usa.gov/1aCh2rT
bullet
ASCO 2013: Comparative outcomes of splenectomy and rituximab-based chemotherapy in elderly patients with splenic marginal zone lymphoma.
 


Workup for Splenic Marginal Zone Lymphoma
(adapted from NCCN Guidelines 2010)

bullet

Staging tests:
 
bullet

CT of Chest/abdominal/pelvic with contrast of diagnostic quality

bullet

Bone marrow biopsy + aspirate (if multifocal disease)

bullet

Useful in select cases:
 
bullet

Additional imaging as indicated by exams / patient reporting

bullet

PET-CT imaging
 

bullet

Physical exam
 
bullet

Performance status

bullet

B symptoms (patient reported)
 

bullet

Labs and tests:
 
bullet

CBC, differential, platelets,

bullet

LDH

bullet

Comprehensive metabolic panel

bullet

SPEP and/or immunoglobulin levels

bullet

Hepatitis B test (if Rituxan considered)

bullet

Hepatitis C test

bullet

Useful in select cases:
 
bullet

Cryoglobulins
 

bullet

Treatment, age and gender specific:
 
bullet

MUGA scan / echocardiogram" 
(prior to anthracycline-based therapy)

bullet

Discuss fertility issues

bullet

Pregnancy testing in women of child-bearing age if chemo is planned

About Splenic Marginal Zone Lymphoma (SMZL) 

  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 
  4. Non-gastric Marginal Zone B-cell Lymphoma in Korea: Clinical Features, Treatment, and Prognostic Factors  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932933/
  5. Hum Pathol., 2010 - technical: Defining the Borders of Splenic Marginal Zone Lymphoma: A Multiparameter Study
  6. CancerNetwork: Splenic Marginal Zone Lymphoma: Current Knowledge and Future Directions

    Detailed information about diagnosis and treatment - including watch and
    wait, and antiviral therapy for SMZL associated with active HCV infection,
    and Splenectomy.
  7. SMZL - CancerNetwork: Splenic Marginal Zone Lymphoma: Current Knowledge and Future Directions
Return to top

Treatment

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]

"French authors reported on a series of 18 patients with splenic lymphoma with villous lymphocytes associated with type II cryoglobulinemia and HCV infection,8 some of whom were responsive to antiviral treatment. " [4]

According to NCCN guidelines (2011), the appropriate treatment (when indicated) depends in part on test results for Hepatitis C and guidance from a Hepatology consult if Hep C positive. Otherwise, except for splenectomy or Rituxan mono-therapy as first treatment, SMZL is treated like follicular lymphoma.

Treatment of splenic marginal zone lymphoma: splenectomy versus rituximab.
Bennett M, Schechter GP.

Source Department of Hematology, Ha'Emek Medical Center, Afula, Israel.

Abstract

Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell lymphoma causing marked splenic enlargement with CD20-rich lymphoma cells infiltrating blood and bone marrow. In the pre-rituximab era, the treatment of choice for patients with symptomatic splenomegaly or threatening cytopenia was splenectomy, since chemotherapy had limited efficacy.

Responses to splenectomy occurred in approximately 90% of patients. However, SMZL patients are often elderly and poor surgical risks.

Since approval of rituximab, treatment of such patients with the anti-CD20 antibody both alone or in combination with chemotherapy has shown remarkable responses. In retrospective series of rituximab monotherapy totaling 52 patients, including both chemotherapy-naive and -refractory patients, overall responses of 88% to 100% were noted with marked and prompt regression of splenomegaly and improvement of cytopenias.

Sustained responses occurred both with and without rituximab maintenance in 60% to 88% of patients at 3 years. Relapsed patients responded to second courses of rituximab monotherapy.

Overall survival was comparable to that reported following splenectomy. Rituximab in combination with purine nucleosides may provide further improvement in progression-free survival; however, confirmatory prospective trials are necessary.

These results suggest that splenectomy should no longer be considered as initial therapy for SMZL but rather as palliative therapy for patients not responsive to immunotherapy with or without chemotherapy.

PMID:20350661

Return to top

More Resources and Reports on SMZL:

  1. SMZL - CancerNetwork: Splenic Marginal Zone Lymphoma: Current Knowledge and Future Directions

    REVIEW ARTICLE

    Splenic Marginal Zone Lymphoma: Current Knowledge and Future Directions

    By Catherine Thieblemont, MD, PhD1, et al, February 9, 2012

    New Therapeutic Strategies in SMZL cancernetwork.com

    "Treatment is required only in symptomatic patients with painful splenomegaly, with or without associated cytopenia due to hypersplenism. Asymptomatic patients, who constitute a large percentage of patients, can be appropriately managed with watchful waiting for several years.

    Withholding treatment does not influence the course of disease, and these patients often have stable disease for at least 10 years.[7] The only exception to this management approach is in the setting of SMZL associated with active HCV infection. "


    On this report Mike (a survivor on nhl-MALT) writes:

    Of note, the attached paper also references 2 other recent SMZL papers at the bottom.  For those of us with the splenic sub-type, reading all 3 gives a full and slightly different approach to the same topic.

    One of the papers features Dr's Leonard and Martin at Weill-Cornell, describing
    encouraging preliminary results using Bendamustine with R for smzl, among other options not limited to (but including) splenectomy.

    The other paper described the recently found genetic mutation in HCL (June 2011) if my memory serves me correctly). Although the 2 conditions appeared to be very similar, patients with SMZL are all testing negative for the HCL mutation. I still continue to follow papers on HCL since some of their treatments (e.g. Cladribine) have also shown effectiveness for SMZL.

    Another recent article of note was ASH-2712 from the December ASH meetings in San Diego. This article discussed the use of R monotherapy in SMZL specifically (encouraging results).

    The good news is that there are already plenty of options. The challenge seems
    to be that there's still much to be learned about the underlying genetics of
    SMZL. Even if these challenges are not figured out in the near future, I expect that new -mabs (e.g. GA-101) and Btk inhibitors will improve life with SMZL in the not too distant future. If one of the main signaling pathways is in fact NF-kB, I believe that has commonality with several other  B-cell lymphomas.
  2. 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."
  3. Comparative study of marginal zone lymphoma involving bone marrow. Am J Clin Pathol. 2002 May;117(5):698-708. PMID: 12090417  PubMed
  4. Splenic Marginal Zone Lymphoma Associated With Hepatitis B Virus Infection: A Case Report  ispub.com 
  5. Splenic marginal zone lymphoma: hydra with many heads? http://bit.ly/lAWHaV 

    Another important issue is the role of hepatitis C virus (HCV) infection in SMZL. ...
  6. Treatment of splenic marginal zone B-cell lymphoma: an analysis of 81 patients.  http://www.ncbi.nlm.nih.gov/pubmed/12141954
  7. Treatment of splenic marginal zone lymphoma: splenectomy versus rituximab http://www.ncbi.nlm.nih.gov/pubmed/20350661
  8. Significant efficacy of 2-CdA with or without rituximab in the treatment of splenic marginal zone lymphoma (SMZL) http://annonc.oxfordjournals.org/content/21/4/851.long

Return to top

Cutaneous Marginal Zone Lymphoma (PCMZL or MZCL)

PCMZL or MZCL
Return to top

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 (what it expresses on the cell surface).

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. 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
  6. Primary Cutaneous Marginal Zone B-Cell Lymphoma
    Clinical and Therapeutic Features in 50 Cases  archderm.ama-assn.org pdf

     

Return to top

Parotid Gland Marginal Zone Lymphoma
(Uncommon)

Return to top

Primary parotid gland lymphoma: a case report
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170354/

Nihon Kokyuki Gakkai Zasshi. 2011 Jul
A case of Sjogren syndrome coexistent with MALT lymphoma occurring along the parotid gland and trachea
http://www.ncbi.nlm.nih.gov/pubmed/21842694

Vojnosanit Pregl. 2009 Dec
Clinical, histopathological and immunohistological study of lymphoid disorders in the parotid gland of patients with Sjögren's syndrome.
http://www.ncbi.nlm.nih.gov/pubmed/20095514

Arthritis Rheum. 2005 Sep
Rituximab treatment in patients with primary Sjögren's syndrome: an open-label phase II study.
http://www.ncbi.nlm.nih.gov/pubmed/16142737 

Acta Otorrinolaringol Esp. 2010
Primary non-Hodgkin lymphoma of the parotid gland: Revision of 8 cases
http://www.ncbi.nlm.nih.gov/pubmed/20346432
 
Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
Patients Against Lymphoma, Copyright © 2004,  All Rights Reserved.