"LARGE B-CELL LYMPHOMA":
INTRODUCTION — Diffuse large B-cell lymphoma (DLBCL) is a fast-growing, aggressive form of non-Hodgkin's lymphoma (NHL), a cancer of the body's lymphatic system. The lymphatic system includes the tissues and organs (including the bone marrow, spleen, thymus and lymph nodes) that produce and store cells that fight infection. Although there are more than 20 types of NHL, DLBCL is the most common type, making up about 30 percent of all lymphomas  . In the United States, DLBCL affects about 5 people out of 100,000 each year  .
Diffuse large B-cell lymphoma can be fatal if left untreated, but with timely and appropriate treatment, up to half of all patients are curable. The following discussion will review the risk factors, classification, clinical symptoms, and prognosis of this type of non-Hodgkin's lymphoma.
RISK FACTORS — Age, gender, and race/ethnicity affect a person's likelihood of developing diffuse large B-cell lymphoma. Although DLBCL has been found in people of all age groups, it is found most commonly in people who are middle-aged or elderly. The average age at the time of diagnosis is 64 years. Men are slightly more likely to develop DLBCL than women. People who are white are more likely to develop this type of lymphoma than people of African or Asian race/ethnicity.
CLASSIFICATION — Diffuse large B-cell lymphoma is a cancer of B lymphocytes. The lymph organs include the bone marrow, thymus, spleen, and lymph nodes. These help to fight infection throughout the body. The organs of the lymphatic systems are connected by a network of lymphatic and blood vessels, through which lymphatic fluid flows. Lymphatic fluid contains white blood cells called lymphocytes (show figure 1).
There are two primary types of lymphocytes: B-cells and T-cells. Almost all lymphocytes begin growing in the bone marrow or lymph nodes. T-cells leave the bone marrow before they are completely matured, and finish maturing in the thymus gland. However, B-cells continue to develop and mature in the bone marrow and lymph nodes.
In DLBCL, the abnormal B-cell lymphocytes are larger than normal. The presence of these large cells characterizes DLBCL; typically, the large cells present in DLBCL have nuclei at least twice the size of small lymphocytes. Researchers have identified several variants of DLBCL, including a centroblastic variant, immunoblastic variant, anaplastic variant, T-cell histiocyte rich large B-cell lymphoma, and T-cell infiltration. It is not clear whether understanding the differences between these variants can improve patients' symptoms or overall prognosis.
Genetic events and chromosomal abnormalities are suspected to be related to the development of DLBCL. In 30 percent of cases of diffuse large B-cell lymphoma, an abnormal transfer (translocation) of part of a chromosome occurs (the t(3;14) gene translocation). This translocation causes a rearrangement in a gene called BCL-6. As a result, the abnormal gene signals the body to produce a protein that alters the growth and development of these cells  .
PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA — Patients with this subtype of DLBCL have tumors within the chest cavity that usually involve the thymus, the gland of the immune system that is located in the front upper middle of the chest and extends from the base of the throat to the front of the heart.
Primary mediastinal large B-cell lymphoma comprises 7 percent of all diffuse large B-cell lymphomas and accounts for 2.4 percent of all non-Hodgkin's lymphomas. Women are slightly more likely to develop this disorder, and the median age of diagnosis occurs in the fourth decade of life.
People who have this form of DLBCL usually present to their physicians with a malignant tumor in the chest cavity that causes difficulty breathing and a condition known as superior vena cava syndrome. If this subtype of diffuse large B-cell lymphoma recurs, it can cause problems with other organs, including the liver, gastrointestinal tract, kidneys, ovaries, and central nervous system.
This type of tumor is aggressive, but it is treatable with programs that combine chemotherapy and radiation.
SYMPTOMS — The first noticeable symptom that patients with diffuse large B-cell lymphoma experience is a quickly growing mass, which may be found either in the neck, groin, or abdomen.
In about one in five patients, tumors caused by DLBCL are confined to one part of the body. However, in about 40 percent of people diagnosed with this type of NHL, the cancer spreads from the lymph system into adjacent organs, a condition known as extranodal infiltration. In some patients, DLBCL spreads to the bone marrow.
DIAGNOSIS — Physicians confirm a diagnosis of DLBCL by removing an enlarged lymph node or a portion of an involved organ in a procedure known as a biopsy. This procedure may be performed under a local anesthetic if the involved tissue is relatively close to the surface. In other cases, a sample of tissue must be obtained under a general anesthetic. The cells from the removed tissue are then examined in detail, using a number of different techniques to determine the nature of the abnormal cell.
Physicians also order blood tests, x-rays, imaging scans, and bone marrow samples to obtain more information about the type of lymphoma and the extent to which it has spread in the body, a process termed "staging" (show table 1). The results of these tests will help physicians decide on the most effective course of treatment. As an example of the importance of staging, treatment of diffuse large B-cell lymphoma is generally more likely to provide a cure when the lymphoma is localized than when it has spread to other parts of the body.
Gene studies, such as the use of gene expression profiling, may allow clinicians to determine which patients have a reduced chance of remission after standard treatments and could suggest which patients would be candidates for more aggressive treatment  . These studies are investigational and are not yet part of standard practice.
TREATMENT — The standard of treatment of DLBCL is combination chemotherapy, occasionally with the addition of radiation to areas of large, bulky disease. The most common chemotherapeutic program for patients with advanced disease consists of 5 medicines (called CHOP-rituximab or CHOP-R) given every three weeks for 6 to 8 cycles. Patients with only localized disease may be treated with fewer cycles of chemotherapy in combination with radiation therapy to the involved area.
PROGNOSIS — The five-year survival rate of patients with DLBCL is between 26 and 73 percent, meaning that between one quarter and three quarters of patients with DLBCL will be disease-free for five years after diagnosis. Relapses tend to occur within the first two to three years after the diagnosis of DLBCL; the disease rarely recurs if the patient has been disease-free for four or more years.