Lymphomas are malignancies of lymphoid tissue. 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. They are classified as either Hodgkin or non-Hodgkin lymphoma.
Non-Hodgkin lymphomas (NHL) are characterized as B-cell (90%) or T-cell lymphomas, depending on the lymphoid cell of origin. The classification of NHL has more than 40 distinct subtypes.
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. Less aggressive cancers may not need immediate treatment and have a more indolent course. These indolent lymphomas are generally not curable, but patients can live decades after initial diagnosis.
Hodgkin lymphoma (HL) is characterized by the histologic presence of the Reed-Sternberg cell. There are 5 types of HL, 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.
Overall, HL currently has a cure rate of more than 85%. The various subtypes 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 (e.g., Agent Orange) and other organic chemicals have been linked to an increased risk.,
- Immune disorders: These include immune deficiency states, chronic immunosuppression, and autoimmune 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 HL and, at least among young patients, a 7-fold increased risk among siblings of HL patients. Although associations between certain HLA haplotypes and risk of HL 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 HL. Other infectious etiologies may also play a role.
- Immune disorders: Immune deficiency states (such as HIV infection), chronic immunosuppression, and autoimmune diseases are also risk factors for HL, although less so than in NHL.
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 with computerized tomography are typically used for both initial staging and assessment of treatment response.
Radiation and/or chemotherapy are the mainstays of treatment. Aggressive NHL types and advanced HL require combination chemotherapy. In cases of bulky disease, radiation therapy to the affected area may be considered. Localized HL is treated with radiation therapy to the affected area.
As the cure rate of HL 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 NHL patients with indolent histologies.
Bone marrow transplantation is an option for some patients.
A limited number of 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 concluded that individuals eating the most red meat had a 10% greater risk of NHL when compared with those eating the least, and for diffuse B-cell lymphoma, this risk increased to 20%. Those consuming high amounts of red meat also had a 17% increased risk for diffuse large B-cell lymphoma specifically.
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, although no consistent associations between red and processed meat and lymphoma risk were observed in this cohort.
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 looking at women who ate beef, pork, or lamb daily found that those who ate these foods daily had more than twice the risk for NHL when compared with those who ate them less than once per week.
In one meta-analysis, the risk for NHL was roughly 25% greater for persons who drank the most milk, compared with those who drank the least. Echoing these findings, another meta-analysis of 16 studies revealed that those who consumed the most milk had a 41% higher risk of NHL when compared with those who consumed the least, although yogurt was associated with a 22% lower risk. The authors also found a dose-response relationship for total dairy product and milk consumption and NHL, with a 5% and 6% increase in risk, respectively, for every 200 additional grams consumed.
Reducing intake of saturated fat and trans fats. One case-control study revealed that high saturated fat intake is significantly associated with Hodgkin lymphoma. In a case-control study of diet and NHL including 1,642 NHL cases and 5,039 controls, individuals in the highest tertiles of total, saturated, and monounsaturated fat intake had approximately 50% higher risk compared with those in the lowest tertiles. In the Nurses’ Health Study, women in the highest quintile of trans fat consumption had 2.4 times the risk of NHL, 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 to be 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 NHL.
High vitamin A and C intakes. The observed benefits of fruits and vegetables in relation to lymphoma prevention may be in part 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 of 22 prospective studies found that each 5 kg/m2 increase in BMI was significantly associated with a 6% increase in NHL risk. Weight in early adulthood (age 18-21 years) may be even more important, as every 5 kg/m2 increase in BMI in this window corresponded with an 11% increase in NHL in the follow-up period.
See Basic Diet Orders chapter.
What to Tell the Family
Lymphoma is a complex group of more than 40 subtypes 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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