|Non-Hodgkin's Lymphomas (NHL)|
|Classification and external resources|
Micrograph of mantle cell lymphoma, a type of non-Hodgkin lymphoma. Terminal ileum. H&E stain.
The non-Hodgkin lymphomas (NHLs) are diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive.
Lymphomas are types of cancer derived from lymphocytes, a type of white blood cell. Lymphomas are treated by combinations of chemotherapy, monoclonal antibodies, immunotherapy, radiation, and hematopoietic stem cell transplantation.
Non-Hodgkin lymphomas were classified according to the 1982 Working Formulation which recognizes 16 types. The Working Formulation is now considered obsolete, and the classification is commonly used primarily for statistical comparisons with previous decades. The Working Formulation has been superseded twice.
The latest lymphoma classification, the 2008 WHO classification, largely abandoned the "Hodgkin" vs. "Non-Hodgkin" grouping. Instead, it lists over 80 different forms of lymphomas in four broad groups.
A number of peer-reviewed health studies have shown a causal link between non-Hodgkin lymphoma and exposure to polychlorinated biphenyls (PCBs), a persistent organic pollutant now found throughout the natural environment.
|This section does not cite any references or sources. (October 2012)|
Hodgkin lymphoma (HL, Hodgkin disease), described by Thomas Hodgkin in 1832, was the first form of lymphoma described and defined. Other forms were later described and there was a need to classify them. Because Hodgkin lymphoma was much more radiation-sensitive than other forms, its diagnosis was important for oncologists and their patients. Thus, research originally focused on it. The first classification of Hodgkin lymphoma was proposed by Robert J. Luke in 1963.
While consensus was rapidly reached on the classification of Hodgkin lymphoma, there remained a large group of very different diseases requiring further classification. The Rappaport classification, proposed by Henry Rappaport in 1956 and 1966, became the first widely accepted classification of lymphomas other than Hodgkin. Following its publication in 1982, the Working Formulation became the standard classification for this group of diseases. It introduced the term non-Hodgkin lymphoma (NHL) and defined three grades of lymphoma.
However, NHL consists of 16 different conditions that have little in common with each other. They are grouped by their aggressiveness. Less aggressive non-Hodgkin lymphomas are compatible with a long survival while more aggressive non-Hodgkin lymphomas can be rapidly fatal without treatment. Without further narrowing, the label is of limited usefulness for patients or doctors.
Contributing factors 
Non-Hodgkin lymphoma and HIV 
The Centre for Disease Control and Prevention (CDC) included certain types of non-Hodgkin's lymphoma as AIDS-defining cancers in 1987. Immune suppression rather than HIV itself is implicated in the pathogenesis of this malignancy, with a clear correlation between the degree of immune suppression and the risk of developing NHL. HIV-infected patients are at an increased risk for developing both Hodgkin lymphoma and NHL when compared with the general population. Another prominent example of AIDS defining malignancy is Kaposi sarcoma, which is not a lymphoma.
Modern usage of term 
Nevertheless, the Working Formulation and the NHL category continue to be used by many. To this day, lymphoma statistics are compiled as Hodgkin's vs non-Hodgkin lymphomas by major cancer agencies, including the National Cancer Institute in its SEER program, the Canadian Cancer Society and the IARC.
Non-Hodgkin lymphoma and PCBs 
A growing number of peer-reviewed, epidemiologic health studies suggest that the rising incidence of non-Hodgkin lymphoma in recent decades may be at least partially due to incidental exposure to organochlorines such as polychlorinated biphenyls (PCBs). PCBs were widely used as dielectric and coolant fluids in transformers, capacitors, and electric motors. Due to the toxicity of PCBs and their classification as persistent organic pollutants, PCB production was banned by the U.S. Congress in 1977 and by the Stockholm Convention on Persistent Organic Pollutants in 2001. Though they are no longer produced, PCBs do not readily break down once they have been released into the environment.
Patients no longer responding to treatment 
According to the US National Cancer Institute 69 000 new cases of non-Hodgkin's Lymphoma are diagnosed each year and 19 000 die from the disease. Cancer cells modify over time and after years some patients no longer responds to treatment. Change of pharmaceutical is often of limited benefit as they all attach to the CD20 antigen on the cancer cells. Cancer cells without this antigen will continue to grow. B-cell non-Hodgkin's Lymphomas also express other antigens like CD19, CD22, CD23, CD37, CD52, CD80 and HLA-DR of which CD37 seems the most interesting. Pharmaceuticals attaching to the CD37 antigen are assumed to efficient. Betalutin, using CD37 conjugated to a radioactive beta emitter , is now in clinical trial. Preliminary data indicate strong antitumor activity. A cross-fire effect from beta radiation also kills cancer cells close by in a tumor not expressing any of the targetable antigens.
See also 
- Lymphoma, for information about all forms of NHL as well as Hodgkin's lymphoma
- Chemotherapy, for information on the standard of care of all forms of non-Hodgkin lymphomas.
- CHOP-R for the most common chemotherapeutic regimen for non-Hodgkin lymphoma.
- "non-Hodgkin lymphomas " at Dorland's Medical Dictionary
- Swerdlow, Steven H; Campo, Elias; Harris, Nancy Lee; Jaffe, Elaine S.; Pileri, Stefano A.; Stein, Harold; Thiele, Jurgan; Vardiman, James W., eds. (2008). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Oxford Univ Pr. ISBN 978-92-832-2431-0.[page needed]
- Kramer, Shira; Hikel, Stephanie Moller; Adams, Kristen; Hinds, David; Moon, Katherine (2012). "Current Status of the Epidemiologic Evidence Linking Polychlorinated Biphenyls and Non-Hodgkin Lymphoma, and the Role of Immune Dysregulation". Environmental Health Perspectives 120 (8): 1067–75. doi:10.1289/ehp.1104652. PMC 3440083. PMID 22552995.
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- "Sewage sludge is probably a source".
- "EPA admits non-Hodgkin lymphoma link to PCB & sludge".
- Centers for Disease Control (1987). "Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases". Morbidity and Mortality Weekly Report 36 (Suppl 1): 1S–15S. PMID 3039334.
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- "International Agreements and Treaties on Pesticides", Pesticides: International Activities, U.S. Environmental Protection Agency. Retrieved 24 August 2012.
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- Non-Hodgkin Lymphoma at American Cancer Society
- Non-Hodgkins Lymphoma from Cancer.net (American Society of Clinical Oncology)
- Patient information on non-Hodgkin lymphoma
- non-Hodgkin in Brain MR Scans of Primary Brain Lymphoma
- Lymphoma Association – Specialist UK charity providing free information and support to patients, their families, friends and carers