Lymphomas are a group of malignancies of lymphoid tissue. They are classified as either Hodgkin or non-Hodgkin lymphoma. While lymphomas generally affect lymph nodes or lymphoid tissue, such as the spleen, they can also affect extranodal tissue, such as the lung, liver, or gastrointestinal tract. They are the most common form of hematologic cancer in the developed world and represent about 5% of all cancers in the US.
Non-Hodgkin lymphomas (NHL) are characterized as B-cell (90%) or T-cell lymphomas, depending on the lymphoid cell of origin. The classification of non-Hodgkin lymphoma has more than 40 separate diagnoses.
The presentation of NHL is highly variable and can have an acute onset with a rapidly enlarging mass, constitutional symptoms (e.g., fever, night sweats and weight loss) and/or laboratory abnormalities (e.g., elevated serum LDH and uric acid). It can also present insidiously with slowly enlarging lymph nodes, hepatomegaly and/or splenomegaly and progressive cytopenias.
Untreated, the most aggressive forms have an extremely poor prognosis, with survival measured in weeks or months. However, with appropriate treatment, many aggressive cases are curable. On the other hand, the less aggressive cancers may not need immediate treatment, but are generally not considered curable.
Hodgkin lymphoma (HL) is characterized by the histologic presence of the Reed-Sternberg cell. There are 5 types of Hodgkin lymphoma, differentiated by histologic appearance:
- Nodular sclerosing
- Mixed cellularity
- Lymphocyte depletion
- Lymphocyte-rich (classical Hodgkin disease)
- Nodular lymphocyte-predominant
HL most often presents as a painless adenopathy or mass. A mediastinal mass on chest x-ray is the second most common presentation. Some patients develop constitutional symptoms such as fever, night sweats, weight loss, and pruritis prior to presentation.
Overall, Hodgkin lymphoma currently has a cure rate of more than 85%. The various types are generally treated similarly and have comparable outcomes
- Increasing age. Although the disease occurs in all age groups, incidence rises dramatically after age 50.
- Family history. Individuals with one or more affected first-degree relatives have twice the usual risk.
- Environmental exposures: Herbicides, pesticides, hair dyes, dioxins (Agent Orange) and other organic chemicals have been linked to an increased risk. ,
- Immune disorders: These include immune deficiency states, chronic immunosuppression, and auto-immune diseases.
- Infectious agents: Viral (e.g., HIV, Epstein-Barr virus, human T-cell lymphotropic virus type I, human herpes virus type 8) and bacterial ( H pylori) infections have been associated with an increased risk of specific types of lymphoma.
- Age. There is a bimodal age distribution with peak incidence in young adults (ages 15-35) and in individuals older than 50.
- Male gender. The condition is more prevalent in males, especially in children and younger adults.
- Geography. Incidence increases in areas with high industrial development.
- Genetics. There is nearly a 100-fold increased risk in monozygotic twins of individuals with Hodgkin disease and, at least among young patients, a 7-fold increased risk among siblings of Hodgkin disease patients. Although associations between certain HLA haplotypes and risk of Hodgkin disease have been identified, it remains unclear whether the increased familial risk is due to a genetic susceptibility or common environmental exposures.
- Infectious agents: Several associations have suggested a link between Epstein-Barr virus and Hodgkin disease. Other infectious etiologies may also play a role.
- Immune disorders: Immune deficiency states (such as HIV infection), chronic immunosuppression, and auto-immune diseases are also risk factors for Hodgkin lymphoma, although less so than in non-Hodgkin lymphoma.
Biopsy of a lymph node or extranodal site of involvement is diagnostic. Histologic findings determine the type and classification of lymphoma.
In many cases, a bone marrow biopsy will be performed to assess marrow involvement. Integrated positron emission tomography (PET) with CT scans typically used for both initial staging and assessment of treatment response.
Radiation and/or chemotherapy are the mainstays of treatment. Aggressive non-Hodgkin lymphoma types and advanced Hodgkin lymphoma require combination chemotherapy. In cases of bulky disease, radiation therapy to the affected area may be considered. Localized Hodgkin lymphoma is treated with radiation therapy to the affected area.
As the cure rate of Hodgkin disease has improved, research has focused on decreasing the toxicity and long-term consequences of treatment, especially second malignancies.
Observation alone without specific treatment is common in asymptomatic non-Hodgkin lymphoma patients with indolent histologies.
Bone marrow transplantation is an option for some patients.
Only a limited number of research studies have addressed associations between diet and risk for lymphoma. The following factors have been under study for possible roles in reducing risk:
Reducing or avoiding intake of animal products. A meta-analysis of red meat intake and risk for NHL concluded that individuals eating the most red meat had a 10% greater risk when compared with those eating the least. This risk increased to 17% in frequent consumers of processed red meat, and increased still further to 20% for diffuse large B-cell lymphoma. In the European Prospective Investigation into Cancer and Nutrition study, a high (compared with low) intake of poultry was associated with a 22% greater risk for B-cell lymphoma.
The NIH-AARP study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial did not support a role for meat intake in lymphoma. However, previous research that compared individuals who ate beef, pork, or lamb daily found that those who eat these foods daily had more than twice the risk for non-Hodgkin lymphoma when compared with those who ate these less than once per week. The risk for NHL was roughly 25% greater for persons who drank the most milk, compared with those who drank the least.
Reducing intake of saturated fat and trans fats. Most studies that have examined associations between fat intake and lymphoma have revealed that saturated fat is the type of fat most often associated with this cancer.
In a case-control study of diet and non-Hodgkin lymphoma, individuals in the highest tertiles of total, saturated, and monounsaturated fat intake had approximately 50% higher risk, compared with those in the lowest tertile. In the Nurses’ Health Study, women in the highest quintile of trans fat consumption had 2.4 times the risk of non-Hodgkin lymphoma, compared with those in the lowest quintile.
Increasing intake of fruits and vegetables. When the highest category of fruit and vegetable intake was compared with the lowest, a meta-analysis found a roughly 20% lower risk for NHL in high consumers, a difference that appeared due mainly to vegetable rather than fruit intake. Previous research that compared women eating 3 daily servings of fruits and vegetables with those who ate 6 or more servings per day found the higher consumers had a 40% lower risk for non-Hodgkin lymphoma.
High vitamin A and C intakes. The observed benefits of fruits and vegetables in relations to lymphoma prevention may be largely attributable to vitamin C and pro-vitamin A carotenoids. In the Women’s Health Initiative study, total vitamin A intake (from foods and supplements) was inversely related to the risk for NHL, while total vitamin C intake was inversely related to the risk for large B-cell lymphoma.
A gluten-free diet for individuals with celiac disease. Patients with celiac disease have a 25% greater risk for malignancy overall, a 60% greater risk for gastrointestinal malignancy, a 14 times greater risk for small intestine carcinoma, and a 6-9 times greater risk for NHL when compared with the general population. The risk for cancer overall is reduced considerably with a gluten-free diet, but poor adherence to such a diet is a risk factor for enteropathy-associated T-cell lymphoma. Even in individuals who adhere to such a diet, the risk for NHL is still 6 times that of the general population. Patients with dermatitis herpetiformis, a condition often experienced by individuals with celiac disease, have a risk for NHL that is up to 10 times greater than those without this skin condition. These individuals also more frequently develop other lymphomas of both the B-cell and T-cell varieties, although this risk is reduced by following a gluten-free diet.
Maintenance of a healthy weight. Studies suggest that being significantly overweight or obese may increase the risk for lymphomas. In overweight and obese persons, the risk for diffuse large B-cell lymphoma was found to be 14% and 29% greater, respectively. A meta-analysis concluded that persons with a 5 kg/m 2 increase over normal bodyweight increases risk for NHL by 7%.
What to Tell the Family
Lymphoma is a complex group of over 40 diseases with widely differing treatments and prognoses. In general, lymphomas are highly treatable, and most patients survive beyond 5 years. Limited evidence suggests that low-fat, plant-based diets may reduce the risk of this disease. It is not yet known whether dietary factors can influence its course.
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