Mantle Cell Lymphoma (MCL) gets its name from the mantle zone, which is the outer edge of lymph nodes where changes take place that lead to this cancer. It wasn’t until recently that mantle cell lymphoma was recognized as a distinct form of [non-Hodgkin] B-cell lymphoma [(NHL)]. Once doctors understood how it is different, they were better able to treat it.

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[The cause is unknown and no inherited predisposition has been identified. MCL is not communicable. It essentially is an abnormal break and subsequent translocation in a gene that causes the cells to divide too early before becoming capable of helping to fight diseases. In addition, the cells do not die as they should and therefore accumulate in the lymphatic system, including lymph nodes and the spleen, with non-useful cells eventually rendering the system dysfunctional. MCL affected cells proliferate in a nodular or diffuse pattern with two main cytologic variants: typical or blastic. Typical cases are small to intermediate sized cells with irregular nuclei. Blastic (aka blastoid) variants have intermediate to large sized cells with finely dispersed chromatin and are more aggressive in nature. MCL is one of the few NHLs that can cross the boundary into the brain, yet it can be treated in that event. http://en.wikipedia.org/wiki/Mantle_cell_lymphoma ]

Doctors had observed that in some people with B-cell lymphoma, the cancer grew much more quickly. However, it was difficult to figure out why, or how to know which patients would be affected in that way. During the past decade, there were a series of breakthroughs, as researchers figured out that a number of people with B-cell lymphoma shared a particular genetic mutation, or change.

Researchers discovered that most people with mantle cell lymphoma have a mutation in two of their chromosomes, the strands of genes that shape all of our characteristics. In mantle cell lymphoma, parts of chromosomes 11 and 14 exchange places, what doctors call a translocation [t(11:14) - -(t(11;14)(q13;q32)]. This translocation leads to the release of too much of a substance called cyclin D1. A buildup of cyclin D1 leads to the uncontrollable growth of a type of B cell and mantle cell lymphoma. An excess of cyclin D1 is almost always found in the lymph nodes of people with mantle cell lymphoma. Another important research finding was that mantle cell lymphoma could be identified through either the presence or absence of B-cell markers on the surface of mantle cell lymphoma cells. There are several types of markers associated with mantle cell lymphoma: CD5, CD19, and CD20. The absence of other B-cell markers, such as CD23 and CD10, is also used to identify mantle cell lymphoma.

Armed with this information, researchers worldwide have joined to look back at a large number of patients who, in the past, were diagnosed with B-cell non-Hodgkin lymphoma. Based on information in these records, doctors can now isolate the cases of mantle cell lymphoma to better understand its course and how it differs from other non-Hodgkin lymphomas.

http://www.cancercare.org/

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Lymphoma

http://www.labtestsonline.org/understanding/conditions/lymphoma.html

[NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated [at the Lab Tests Online website] as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.]

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height=432 Lymphoma is a cancer of certain types of white blood cells (WBCs) called lymphocytes. These cells circulate throughout the body in the blood stream and in the lymphatic system, which is part of the body’s immune system. There are several different types of lymphocytes, the major types being the B-lymphocyte and the T-lymphocyte.

T-lymphocytes can be thought of as the controllers of the immune system. They initiate the immune response, control how big or small it should be, and shut it down when it’s not needed. In addition, they can neutralize several different types of foreign attackers. B-lymphocytes make antibodies. It is these cells that are activated when a person is vaccinated against diseases such as measles, mumps, or hepatitis. Natural killer (NK) cells are also a type of lymphocyte and make up about 10-15% of total lymphocytes in the blood. NK cells attack and "kill"” abnormal cells such as cancer cells or those infected with viruses.

Any one of these cells or a combination of them can be involved in lymphoma. Lymphoma begins with the production of one or more abnormal cells in one or more of the lymph nodes, areas where lymphocytes congregate. These cells reproduce uncontrollably, begin to outnumber normal cells in the node, lead to the enlargement of the lymph node, and eventually travel to one or more other lymph nodes. They may also spread to and from other lymph-system-related organs including the spleen, bone marrow, tonsils, adenoids, and thymus.

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[Image of Lymphatic System – from Wikipedia.org]

Signs and Symptoms

Patients who have lymphoma may experience painless swelling of the lymph nodes in the armpits, neck, and/or groin. They may experience fatigue, fever, night sweats, unintended weight loss, a loss of appetite, itchiness, and neck or flank pain. If the lymph node is in the chest, it may affect the person’s breathing; if it is in their abdomen, it can cause abdominal discomfort. Lymphoma can sometimes be difficult to diagnose because these signs and symptoms are often mild. Some patients may have no noticeable signs while others might have a low-grade fever. Usually, there are swollen lymph nodes, but the node may not be visible or felt by the patient or physician.

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Types of Lymphoma

There are two primary types of lymphoma: Hodgkin lymphoma (HL, also called Hodgkin’s disease), which is characterized by the presence of large distinctive cells called Reed-Sternberg cells, and non-Hodgkin lymphoma (NHL), a large group of other lymphomas.

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Hodgkin Lymphoma

Hodgkin lymphoma is most prevalent in two age groups: in those between about 25 and 35 years of age and in those over 55. According to the American Cancer Society (ACS), about 8,000 people in the United States are diagnosed with Hodgkin lymphoma in one year and about 1,000 people die of it.

There are many different theories concerning the cause and types of HL. Some think that a type of infectious agent, such as a virus, might be involved. Others think that a mutation in a cell is the cause. While this is an area of active research, specific causes have not yet been identified. Likewise, there is no clear understanding of why males seem to be slightly more susceptible to the disease.

HL can be subdivided based on the structure of the abnormal lymph node and the types of cells that are present. Lymph nodes may have a predominance of small lymphocytes, the presence of bands of fibrosis (scarring), a mixture of cell types, or lymphocyte depletion.

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Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma is the fifth most common cancer in the United States. It is slightly more common in men than women and more common in Caucasians. The incidence of NHL increases with age and is higher in patients with HIV/AIDS and in patients whose immune systems are suppressed. According to the ACS, about 60,000 people are diagnosed with non-Hodgkin lymphoma in one year and about 19,000 people die from it.

There are about 30 different types of non-Hodgkin lymphoma. Over the years, different classification systems have been used to describe the different types of non-Hodgkin lymphoma as knowledge about the condition has grown. New methods of evaluating the cells involved in non-Hodgkin lymphoma have led to changes in classification systems.

The Revised European American Lymphoma (REAL) looks at the function that the cell should be providing. Some lymphocytes (B-lymphocytes) are responsible for producing antibodies while others (T-lymphocytes) are responsible for cell-to-cell interactions. The newest method, the World Health Organization or (WHO) Classification, tries to combine all of these characteristics with genetic studies of the cells.

In the 1990’s, the REAL classification was proposed by the International Lymphoma Study Group and adopted by many physicians. Since that time, the WHO classification has expanded on REAL and has been accepted by many as the current standard. [see Table of Classifications]

Click here to view a table of classifications at LabTestsOnline.org.

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Some Types of Non-Hodgkin Lymphomas

Classification of non-Hodgkin lymphomas can be confusing because there are so many different types and because of the various classification systems that have been developed and amended over the years. In the United States, B-cell non-Hodgkin lymphomas are much more common than T-cell. About 85% of non-Hodgkin lymphomas involve mature B lymphocytes with about 15% affecting T-lymphocytes.

Some of the more common forms of B-Cell lymphomas include:

· Diffuse large B-cell lymphoma (DLBCL): this form constitutes about 33% of all non-Hodgkin lymphomas in the United States. It is a fast growing lymphoma and can affect anyone of any age but occurs mostly in older people.

· Follicular lymphomas: these make up about 14% of all lymphomas in the U.S. This is considered a very slow growing lymphoma.

· B cell chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): these are related diseases because they affect the same type of cell (small lymphocytes). However, CLL is found mainly in the bone marrow and the circulating blood while SLL is found mainly in the lymph nodes. These two together make up approximately 24% of all lymphomas.

Some of the more common forms of T-Cell lymphomas include:

· Precursor T-lymphoblastic lymphoma (leukemia): a disease that can be considered either a lymphoma or leukemia depending on whether affected cells are found in the blood or whether a certain percentage of bone marrow cells are abnormal. About 1% of all lymphomas are this type.

· Mature or peripheral T-cell lymphomas: there are many different kinds of mature T-cell lymphomas that all together make up about 4% to 5% of all lymphomas.

· Mycosis fungoides (Sezary syndrome), also called cutaneous T-cell lymphoma: This is a less common form of lymphoma but is unusual because, while most lymphomas begin in lymphoid tissue or internal organs, this type of lymphoma starts in the skin. It is part of a group of skin cancers that make up less than 1% of nonmelanoma skin cancers.

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Staging

Because more than one lymph node can be involved, it is important to find out which ones are affected and where they are located in the body. This process is called staging. The following table contains an example of a classification system that describes how widespread the disease is.

Stages Found in Lymphomas

I. Stage I occurs when there is a single lymphoid area (such as the spleen), a pair of areas (tonsils), or a group of related areas (the tonsils and adenoids) involved.

II. Stage II occurs when there are two or more lymphoid areas involved, but they are on the same side of the diaphragm (the muscle under the rib cage that controls breathing). An example of this would be the tonsils and one underarm lymph node.

III. Stage III occurs when there is involvement on both sides of the diaphragm, such as a node in the neck and another in the abdomen.

IV. Stage IV has involvement throughout the body and, in particular, in major sites such as the bone marrow.

There is another staging system that uses location and prognostic factors such as age, symptoms, and certain laboratory tests in the development of a three-part system.

Stage I involves one or two sites with none of the poor prognostic signs.

Stage II has more than two sites involved and some poor prognostic signs.

Stage III has widespread disease and significant signs of poor prognosis.

Staging allows the physician to determine what choices of therapy are available. For example, if a patient has Stage I with only one node involved, then surgically removing that node may result in a cure. On the other hand, if the patient is at Stage IV, then surgical removal is not generally possible.

The most commonly used staging tests performed in the clinical laboratory are the CBC (Complete Blood Count,) liver and kidney function studies, and bone marrow biopsy. Non-laboratory tests include CAT (or CT - Computed Tomography) scans, MRI (Magnetic Resonance Imaging) evaluations, and x-ray procedures.

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Testing

The goals with testing are to diagnose and stage lymphoma, to distinguish it from other conditions, and to identify and monitor any associated complications. There are few blood tests that clearly indicate lymphoma.

The gold standard diagnostic test for both HL and NHL is the examination of lymph tissue by a pathologist (specialist). The sample is usually collected from an affected lymph node using a biopsy or fine needle aspiration procedure and is examined under the microscope. Other laboratory tests that may be useful include:

Laboratory Tests

· Complete Blood Count (CBC) - may be ordered to rule out non-lymphoma conditions (such as leukemia) and/or to see if anemia or low platelet and/or white blood cells counts are present, which may indicate that lymphoma is present in the bone marrow.

· Bone marrow biopsy and examination – to evaluate the cells present in the bone marrow.

· Blood smear – to evaluate the quality of red and white blood cells and platelets.

· Immunophenotyping can identify the cells involved by testing for the presence or absence of surface markers on the membrane of the cells. These markers are called clusters of differentiation (CD) and are listed numerically. By developing a list of the CDs present on the cells, it is possible to classify the cells. This test can be done by several different methods, including flow cytometry and immunohistochemistry.

· Cytogenetics – an evaluation of the chromosomes in the nucleus of cancer cells to determine if pieces of the chromosomes have moved (translocation).

· Molecular genetic analysis – evaluating the cancer cell’s DNA for genetic changes.

Non-Laboratory Tests

Primarily used to help stage and monitor lymphoma. They include:

· Physical examination

· Computed tomography (CT) scans

· Positron emission tomography (PET) scan

· Chest X-ray

· Exploratory surgery (occasionally necessary)

· Magnetic Resonance Imaging (MRI)

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Treatment

Each lymphoma is unique; some are more aggressive than others. The physician will also “grade” the cancer based on its apparent aggressiveness. This information, along with the type and location(s) of the lymphoma, are used to guide treatment. The ultimate goal of treatment is to cure the patient. Where this is not possible, the goals are to put the lymphoma into remission for as long as possible, slow it down, relieve symptoms, and to minimize and address complications. If the lymphoma is in an area that allows for its complete surgical removal, such as confined to a single lymph node, then that is the best choice.

When the lymphoma cannot be completely removed, combinations of cancer chemotherapy and radiation are used. For some cases, high dose chemotherapy followed by stem cell transplantation may be used. Prognosis depends on the stage and grade of the disease and the general health of the patient. All patients, even those whose lymphoma has been “cured” or put into remission, must be monitored for the rest of their lives. Many never experience lymphoma again but in others, it may recur years after the first incidence.

The following table [Table of Classifications] illustrates the two most commonly used classifications plus an older classification. Because of differences in how the lymphomas are described, there is not a one-to-one comparison between the systems, and a single disease could be known by multiple names.

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[quick links to images of the Lymphatic System:]

http://www.healthline.com/vpbody/lymphatic

http://en.wikipedia.org/wiki/Lymphatic_system

http://www.daviddarling.info/encyclopedia/L/lymphatic_system.html

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TABLE OF CLASSIFICATIONS

Comparison of Some Non-Hodgkin Lymphoma Classifications

Note: These classifications cannot always be compared.
*NCI (Working Formulation) (Older Classification)**	REAL**	WHO* Classification**
	B cell lineage/NHL	Mature B cell lymphoma
Low grade lymphoma Small lymphocytic lymphoma (plasmacytoid) Follicular lymphoma (small cleaved cell, large cell, mixed cell) High Grade lymphoma Diffuse lymphoma (small cleaved, large, mixed cell) Diffuse immunoloblastic lymphoma Burkitt Lymphoma Burkitt-like Lymphoma Lymphoblastic lymphoma	B-cell chronic lymphocytic leukemia Lymphoplasmacytic lymphoma Nodal and extranodal marginal B-cell lymphoma Follicular Center, grades I, II, and III lymphoma Mantle Cell lymphoma	B cell CLL / SLL Splenic marginal zone B-cell lymphoma Extranodal marginal B cell lymphoma Follicular lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma Burkitt’s lymphoma
T and NK Cell Neoplasms		T and NK Cell Neoplasms
		Mature T cell lymphoma
Small lymphocyte lymphoma Mycosis Fungoides Diffuse lymphoma (small cleaved, large, mixed cell) Large cell immunoblastic lymphoma		Adult T cell lymphoma Mycosis Fungoides Anaplastic large cell lymphoma not otherwise characterized Immunoblastic T cell lymphoma
		Langerhans cell histiocytosis Langerhans cell sarcoma Interdigitating dendritic cell sarcoma/tumor Follicular dendritic cell sarcoma/tumor Dendritic cell sarcoma, not otherwise specified
* NCI = National Cancer Institute REAL = Revised European American Lymphoma * WHO = World Health Organization

This article was last reviewed on February 14, 2007. | This article was last modified on June 18, 2010.

The review date indicates when the article was last reviewed from beginning to end to ensure that it reflects the most current science. A review may not require any modifications to the article, so the two dates may not always agree.

The modified date indicates that one or more changes were made to the article. Such changes may or may not result from a full review of the article, so the two dates may not always agree.

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Related Pages
On This Site [http://www.labtestsonline.org/]
Tests: CBC, Platelet count, WBC, Bone marrow biopsy, Blood smear, Beta-2 Microglobulin

Elsewhere On The Web
The Lymphoma Information Network
The Leukemia & Lymphoma Society
MedlinePlus Medical Encyclopedia: Hodgkin’s Lymphoma
MedlinePlus Medical Encyclopedia: Non-Hodgkin’s Lymphoma
University of Medicine and Dentistry of New Jersey: Hemepath Tutorial Table of Contents
American Cancer Society: Detailed Guide: Lymphoma, Non-Hodgkin's type
American Cancer Society: Detailed Guide: Hodgkin Disease
Patient list [services] for lymphoma can be found at [the Association of Cancer Online Resources] http://acor.org/. They include specific online patient communities concerned with Hodgkin, Mantle cell, Non-Hodgkin lymphoma or pediatric lymphomas.

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Article Sources

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated [at the Lab Tests Online website] as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

American Cancer Society [On-line information]. Available online at http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=32 through http://www.cancer.org.

(2006 April 20, Revised). Detailed Guide: Hodgkin Disease, What Are the Key Statistics About Hodgkin Disease? American Cancer Society [On-line information]. Available online through http://www.cancer.org.

(2006 May 30). Detailed Guide: Lymphoma, Non-Hodgkin's type, What Are the Key Statistics About Non-Hodgkin Lymphoma? American Cancer Society [On-line information]. Available online through http://www.cancer.org.

Matsui, W. (2006 May 3). Hodgkin’s lymphoma. Medline Plus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000580.htm.

Brose, M. (2004 August 3, Updated). Non-Hodgkin's lymphoma. Medline Plus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000581.htm.

Weissmann, D. (2006 May 18, Revised). Hemepath Tutorial Table of Contents. University of Medicine and Dentistry of New Jersey [On-line information]. Available online at http://pleiad.umdnj.edu/~dweiss/default.html through http://pleiad.umdnj.edu.

(© 2006). Hodgkin Lymphoma (HL): An Overview. University of Medicine and Dentistry of New Jersey [On-line information]. Available online at http://pleiad.umdnj.edu/~dweiss/hd_intro/hd_intro.html through http://pleiad.umdnj.edu.

(© 2006). Introduction to Non-Hodgkin Lymphomas (NHLs). University of Medicine and Dentistry of New Jersey [On-line information]. Available online at http://pleiad.umdnj.edu/~dweiss/lymph_intro/lymph_intro.html through http://pleiad.umdnj.edu.

(© 2006). Classifying Non-Hodgkin’s Lymphomas. University of Medicine and Dentistry of New Jersey [On-line information]. Available online at http://pleiad.umdnj.edu/hemepath/classification/classification.html through http://pleiad.umdnj.edu.

(2003 February 1, Revised). Hodgkin’s Disease. Merck Manual Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec14/ch177/ch177b.html through http://www.merck.com.

(2003 February 1, Revised). Non-Hodgkin’s Lymphomas. Merck Manual Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec14/ch177/ch177c.html through http://www.merck.com.

(2003 February 1, Revised). Biology of the Immune System, Merck Manual Home Edition. Merk Manual Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec16/ch183/ch183a.html#fg183_2 through http://www.merck.com.

Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson, RA, Pincus, MR, eds. New York: Saunders, Elsevier: 2007.

Harrison's Principles of Internal Medicine, Kasper, et al, 16th Edition, McGraw Hill, 2005.

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Types of Lymphoma

Hodgkin Lymphoma

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Some Types of Non-Hodgkin Lymphomas

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Stages Found in Lymphomas

Testing

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Comparison of Some Non-Hodgkin Lymphoma Classifications

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