Non-Hodgkin lymphoma is a heterogeneous group of malignancies of lymphocyte origin that usually arise or are present in lymphoid tissues, such as lymph nodes, spleen, and bone marrow. Nevertheless, lymphomas can arise in any organ and usually are referred to as primary extranodal lymphomas. Microscopically, follicular lymphomas exhibit a follicular or nodular pattern of growth reminiscent of germinal centers. Despite the fact that most follicular lymphomas are advanced at the time of diagnosis, the median survival of patients with follicular lymphomas is approximately 8-10 years, and many patients may not require treatment for prolonged periods of time.
Most lymphomas originate from lymph node tissue and frequently metastasize to other organs. Lymphomas can invade any organ, including the skin and central nervous system. Lymphomas cause detrimental effects by organ invasion and by obstruction of anatomical structures by a tumoral mass. For example, ureteral obstruction by enlarged lymph nodes can lead to renal failure.
Non-Hodgkin lymphoma is the seventh most frequently diagnosed malignancy in the United States. Estimates indicate that more than 56,000 cases of non-Hodgkin lymphoma were diagnosed in 2005. Of those, 15-20% were follicular lymphomas.
In general, age-adjusted incidence rates of non-Hodgkin lymphoma are higher in more developed countries. The age-adjusted incidence rates of non-Hodgkin lymphoma varied from 3.7-14 per 100,000 person years from 1983-1987 in different countries.
The overall survival rate at 5 years is 72-77%. Median survival is approximately 8-10 years.
The Follicular Lymphoma International Prognostic Index (FLIPI) is predictive of survival in patients with follicular lymphomas. Five adverse prognostic factors have been shown to be correlated with reduced overall survival: age older than 60 years, Ann Arbor stage III or IV disease, hemoglobin less than 12 g/dL, presence of more than 4 nodal sites of disease, and serum lactate dehydrogenase above normal. Patients with 3 or more of the above risk factors have a 10-year overall survival rate of 36% compared with 71% for those with one or none of the above variables.
Variations in racial incidence are found throughout the world. The incidence of follicular lymphomas is low in China and Japan. People of Jewish ancestry have a higher incidence of lymphoma. In the United States, the incidence is 2-3 times higher in Caucasians than in African Americans.
The male-to-female ratio is approximately 1:1.
Median age at diagnosis is 60-65 years. The incidence of follicular lymphomas increases with age. Follicular lymphomas are extremely rare in children.
Painless, slowly progressive adenopathy is the most frequent clinical presentation.
Some patients have waxing and waning adenopathy.
Systemic symptoms, such as fever, night sweats, weight loss in excess of 10%, or asthenia, are infrequent at presentation but can be observed in later stages of the disease. Progression to an intermediate-grade or high-grade lymphoma should be considered when a patient develops systemic symptoms.
Symptoms related to bone marrow dysfunction, such as anemia, leukopenia, or thrombocytopenia, are rare at presentation but can be observed in the later stages of the disease.
All lymph node areas should be examined, including the retroauricular, submandibular, cervical, supraclavicular, axillary, epitrochlear, inguinal, and popliteal areas.
Involved nodes typically are nontender, firm, and rubbery in consistency.
Splenomegaly is present in approximately 50% of patients at presentation.
The throat should be examined for involvement of the oropharyngeal lymphoid tissue (ie, Waldeyer ring).
Acquired nonrandom chromosomal translocations
The most common in patients with follicular lymphomas is the t(14;18) translocation, which is found in more than 80% of cases. This chromosomal translocation brings the bcl2 protooncogene under the transcriptional influence of the immunoglobulin heavy-chain gene. This translocation leads to the overexpression of a functionally normal bcl-2 protein. Overexpression of the bcl-2 protein, a protein of the mitochondrial membrane, confers a survival advantage to the cancer cells by inhibiting programmed cell death, or apoptosis. Although the exact mechanism of action of bcl-2 is unclear, its interaction with other homologs is felt to determine the likelihood of a cell undergoing apoptosis.
The detection of the t(14;18) product by polymerase chain reaction is used frequently in the diagnosis and follow-up of patients with follicular lymphomas. Nevertheless, this translocation has been detected in healthy patients and in patients with other types of tumors.
Viruses have been implicated as etiologic factors for lymphomas, including the Epstein-Barr virus, human T-cell lymphotropic virus type I, and the herpesvirus associated with Kaposi sarcoma (ie, human herpesvirus 8). Nevertheless, these viruses have been linked mostly to diffuse or high-grade lymphomas.
Chemicals, such as pesticides and hair dyes, have been associated with lymphoma.
Congenital immunodeficiencies have been associated with lymphoma.
Acquired immunodeficiencies may include infection with the human immunodeficiency virus. Most lymphomas associated with the human immunodeficiency virus are intermediate-grade or high-grade lymphomas.
Patients who have been on immunosuppressant drugs after organ transplantation may develop lymphoma. Most of the lymphomas observed after organ transplantation are diffuse or high-grade lymphomas.