Lymphomas

Overview

     Lymphomas are cancers that start in the lymph nodes.  There are several varieties of lymphomas and they are divided into two broad categories: Hodgkin’s disease and the non-Hodgkin’s lymphomas.  There are about 7,200 new cases of Hodgkin’s disease annually with about 1,300 deaths.  There are about 56,800 new cases of non-Hodgkin’s lymphoma annually with about 25,700 deaths, and the number of new cases of non-Hodgkin’s lymphoma has been increasing in recent years. This is an area where treatment has improved the outlook of cancer patients. Currently, the majority of lymphoma patients will be cured. Treatment will vary with the precise nature and stage of the lymphoma, but will usually include chemotherapy or radiation therapy or both.

In-depth Information

Hodgkin’s Disease

     Hodgkin’s disease draws its name from a description of six cases reported by Thomas Hodgkin in 1832, well before the clear description of any other lymphoma.  Sir Samuel Wilks in 1865 referred to the disease as Hodgkin’s disease, and the name has been retained since then.

     Microscopic tissue examination in Hodgkin’s disease reveals large cells with multiple nuclei known as Reed-Sternberg cells; they are one of the characteristic features of this particular lymphoma.  A partial association of Hodgkin’s disease with infectious mononucleosis and the Epstein-Barr virus has been suggested.  There are four major types of Hodgkin’s disease distinguished by their features under the microscope: lymphocyte predominant, nodular sclerosing, mixed cellularity, and lymphocyte depleted.  The more common types are nodular sclerosing and mixed cellularity.  Lymphocyte predominant is one of the less common types, but it has the most favorable prognosis. The majority of patients are diagnosed at an early stage of the disease, and 90% of the patients will be alive 10 years later.  Treatment may often be less extensive than for the other types.

     Nodular sclerosing Hodgkin’s disease is the most common of the four types.  This type of the disease tends to appear in the neck, chest, and armpits.  The lymphocyte predominant and nodular sclerosing types are sometimes referred to as "favorable histology" because these patients frequently have better outcomes compared to the other two types.  Mixed cellularity Hodgkin’s disease is the second most common type.  Lymphocyte-depleted Hodgkin’s disease is the rarest of the four types, constituting less than 1% of the cases in many reports.  The lymphocyte depleted and mixed cellularity types more frequently have involvement of abdominal sites at the time of diagnosis. Hodgkin’s disease differs from most of the non-Hodgkin’s lymphomas in its tendency to progress in an orderly fashion through the lymphatic system, spreading from the lymph node group of origin to an adjacent group of lymph nodes and then on to the next adjacent group in a sequential manner; this is sometimes referred to as “contiguity theory.”  Contiguity theory figures significantly in the staging system and treatment of Hodgkin’s disease. 

     Both stage and treatment influence the disease-free survival. The staging system most frequently used for Hodgkin’s disease is the Ann Arbor staging system, or one of its close variants.  Stage is determined by the number and distribution of lymph node groups involved, the involvement of other structures in addition to lymph nodes (such as the spleen, bone marrow, liver, and lung), and the presence or absence of “B symptoms" as described below.  The four stages of the Ann Arbor staging system are as follows:

  • Stage I: The most favorable stage. Indicates involvement of a single lymph node region (I), the right armpit, for example, or localized involvement of a single organ or site not in a lymph node (Ie).

  • Stage II: Represents involvement of two or more lymph node groups on the same side of the diaphragm (II) or localized involvement of a single organ and lymph node groups on the same side of the diaphragm (IIe).

  • Stage III: Indicates involvement of lymph node groups on both sides of the diaphragm.  Involvement of a structure outside the lymph nodes is designated as IIIe; a special case of this is the involvement of the spleen (IIIs). 

  • Stage IV: Implies advanced disease with involvement of multiple organs, bone marrow, or a single organ with distant lymph nodes involved.

     The above stages can then be modified by “A” or “B” designations indicating the absence or presence, respectively, of at least one “B symptom.” The possible B symptoms are an unexplained weight loss of more than 10% of body weight in the 6 months preceding diagnosis, unexplained fevers of at least 38o Celsius, or drenching night sweats requiring a change of bedclothes.  Persistent widespread itching was once regarded as a “B symptom”, but it no longer has this designation. 

     Determination of the extent of disease, often referred to as the “staging work-up,” starts with the history and physical examination.  It usually includes various other tests, such as CT scans and bone marrow biopsy.  Historically, the staging of Hodgkin’s Disease that was apparent in the upper half of the body included a staging laparotomy, which is a surgical exploration of the abdomen to confirm that there is no microscopic tumor. Laparotomy is no longer done in most cases if it will not alter treatment.

     Treatment of stages I and II Hodgkin’s disease sometimes is done by radiation therapy alone, and stage IV Hodgkin’s disease is sometimes treated by multiple courses of chemotherapy without radiation therapy.  Many cases of Hodgkin’s disease are treated by a combination of radiation therapy and chemotherapy.  Many cases of stage I and II Hodgkin’s disease in the upper half of the body will receive “mantle” radiotherapy as some or all of the treatment in an attempt to cure the patient.  “Contiguity theory” predicts that the most likely sites to have microscopic deposits of Hodgkin’s disease will be the lymph node groups near the obviously involved lymph nodes.  The mantle field is an irregularly shaped radiation field, thought to resemble the mantle of a medieval knight, that is designed to treat the lymph nodes at risk in the neck, the center of the chest, and the armpits.

     The great majority of patients with Hodgkin’s disease will be cured in their initial course of treatment today, especially if the disease is diagnosed in stage I or II.  However, patients should receive ongoing regular check-ups following treatment for this disease. Recurrence of this disease can often be cured with a second course of therapy.  Hodgkin’s disease patients also have an increased risk of developing a second kind of cancer later in life.

     Several subtypes of the non-Hodgkin’s lymphomas are described below.  There are a large number of classification schemes for these lymphomas, giving them different names.  There are also many uncommon subtypes. 

Diffuse Large Cell Lymphoma

     Diffuse large cell lymphoma is the most common of the group sometimes referred to as the aggressive non-Hodgkin’s lymphomas.  The term aggressive indicates that if the disease were untreated, it would be expected to lead to the patient’s death in a matter of months.  Diffuse large cell lymphoma constitutes about 30% of all cases of non-Hodgkin’s lymphomas.  The same staging system used for Hodgkin’s disease is also used for non-Hodgkin’s lymphomas (see above).  About 40% of patients with advanced stage disease and 80-90% of patients with stage I-II disease are curable by the use of chemotherapy or chemotherapy and radiation therapy.  A common chemotherapy regimen frequently employed is known as CHOP (cyclophosphamide, daunorubicin, vincristine, and prednisone), although there are many similar regimens.

Nodular or Follicular Lymphomas

     Collectively, follicular small-cleaved  or nodular poorly differentiated lymphocytic lymphoma and follicular mixed small-cleaved and large cell lymphoma or nodular mixed lymphocytic and histiocytic lymphoma, are often referred to as "indolent lymphomas" and constitute about 30 % of the non-Hodgkin’s lymphomas.  These lymphomas are considered indolent because even untreated a patient can often survive for several years.  Some experts consider these lymphomas incurable; unfortunately, most patients are diagnosed at an advanced stage with perhaps only 20% of the patients being stage I or II, and patients put into complete remission by active treatment can have disease recurrence many years later.  Approximately half of the nodular lymphoma patients will have bone marrow involved at the time of diagnosis, makeing them stage IV.  Stage I and II patients can be treated in a curative attempt by radiation therapy alone as one principal option.  Regional radiation therapy for stage I and II nodular or follicular lymphomas consists of radiation treatment of the apparently involved lymph node areas plus the adjacent lymph node areas.  The best strategy to deal with stage III and IV follicular lymphomas remains unclear, and recommendations may vary widely.  The majority of stage III and IV patients will eventually die of lymphoma, although the time frame may be in years.  Some doctors will recommend no active treatment until the lymphoma causes symptomatic problems.  At the time symptoms appear, the treatment options consist of single agent chemotherapy, combination chemotherapy, or radiation treatment.   A more aggressive approach would be to undertake multiple courses of combination chemotherapy, with or without radiation therapy, at the time of diagnosis.

Cutaneous T-Cell Lymphoma (Mycosis Fungoides)

     Several clinical pictures once regarded as different diseases are now generally recognized as being just different presenting forms of one disease, cutaneous T-cell lymphoma (skin lymphoma).  These include mycosis fungoides, Sezary syndrome, and reticulum cell sarcoma of the skin. Diagnosis may be difficult because the cutaneous lymphoma may have the appearance of a benign skin disorder.  Also, the Ann Arbor staging system is not appropriate for staging this disease, and several alternate staging systems have been proposed.  In general, very early stage disease would consist of skin plaques covering a limited part of the body with no tumor nodules or major organ involvement. The “red man” with abnormal cells circulating in the bloodstream is characteristic of Sezary syndrome.  Other factors of importance in the staging of cutaneous T cell lymphoma include the involvement of lymph nodes, whether or not abnormal cells are seen in the blood stream, and whether or not major vital organs are involved.  Patients may have skin lesions for 8-10 years before diagnosis.  After diagnosis, the overall survival generally may be 5-10 years, with some improvement in the most recent reports.  The median (average) survival of patients with lymph node involvement at diagnosis is about 2 years and the median survival of patients with vital organ involvement is about 1 year.

     Treatment of cutaneous lymphoma may consist of local radiation therapy or total skin electron beam radiation therapy for disease limited to the skin.  Emory University has a technique available in which a patient is rotated on a platform while an electron beam is scattered by a clear shield to effectively bathe the whole body of the patient in electrons to treat this skin lymphoma.  More advanced stages of the disease are often treated by some form of chemotherapy.

Research & Clinical Trials

     At Emory University, we participate in a number of clinical trials for different types of diseases.  Click here to visit our clinical trials center.

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