Non-Hodgkin Lymphoma - Cancer Institute Overview
The Lymphoma Program of Cleveland Clinic Taussig Cancer Institute is a comprehensive, multidisciplinary effort involving medical oncologists, hematologists, radiation oncologists, surgeons, dermatologists, gastroenterologists, neurologists, radiologists, pathologists, infectious disease specialists, pharmacologists, oncology nurses, social workers, and scientists.
This program is dedicated to the diagnosis, evaluation and treatment of patients with lymphoma; education and support of lymphoma patients and their families and friends; investigation of the cause of lymphoma; and development of innovative treatment for patients with lymphoma both with non-Hodgkin lymphoma, as well as Hodgkin's disease.
Our pathologists now recognize more than three dozen different types of lymphoma, including Hodgkin's Disease, and use the most modern techniques of molecular pathology to characterize them and to help in formulating optimal plans of management. The best treatment for an individual depends upon the specific diagnosis. Cleveland Clinic has pathologists dedicated to the accurate interpretation and classification of each lymphoma biopsy specimen.
What is lymphoma?
Lymphoma is a group of cancers arising from cells of the immune and lymphatic systems. The immune system is body's defense network against disease that includes lymph nodes (the lymphatic system) that remove fluids from tissues. Although these cancers are often discussed together as a single disease, they actually constitute an array of unique entities with widely variable manifestations, behavior, management and prognosis.
Historically, they are divided into two broad categories: "Hodgkin's disease" and "non-Hodgkin's lymphoma." The 2001 World Health Organization classification uses the terms Hodgkin lymphoma and non-Hodgkin lymphoma.
What is non-Hodgkin lymphoma?
Non-Hodgkin lymphoma is a heterogeneous group of cancers, which arise from B lymphocytes (90 percent), T lymphocytes, or rarely NK cells and involve lymph nodes, bone marrow, blood and/or any extralymphatic site. The pattern of dissemination in patients with non-Hodgkin lymphoma is usually unpredictable.
Most patients with non-Hodgkin lymphoma have disseminated disease at the time of diagnosis. Even patients that appear to have localized disease based on standard imaging studies, probably have occult microscopic metastases. Like Hodgkin lymphoma, the manifestations and complications of the disease are due to enlargement of lymph nodes or tumor masses, impingement upon or invasion of normal tissues and organs, and impairment of bone marrow and immune system function.
What are the symptoms of non-Hodgkin lymphoma?
Non-Hodgkin lymphoma may involve any lymphatic or extralymphatic tissue. Consequently, any symptom is possible.
Most patients present with painless enlargement of one or more superficial lymph nodes. These abnormalities may have been present for weeks or months and may have remained stable, progressed, or not uncommonly, even improved (albeit temporarily).
Enlarged lymph nodes in the chest are symptom of lymphoma and may cause chest pain, cough, shortness of breath, or swelling of the face and arms. Enlarged lymph nodes in the abdomen or pelvis or an enlarged spleen may cause discomfort, fullness, loss of appetite, back pain, or swelling of the legs.
Some lymphomas begin in a single organ: lymphoma of the stomach may lead to abdominal discomfort, nausea, vomiting, or internal bleeding; lymphoma of the brain (primary central nervous system lymphoma) may cause headaches, alteration in mental status, seizures, or focal weakness; and lymphoma of the skin may result in localized or extensive skin lesions.
Symptoms may occur due to involvement of less common sites, such as bone, testis, spinal cord, eye, or sinus. Patients may have symptoms of anemia (fatigue, shortness of breath). About 20 percent of patients have "B" symptoms (fever, night sweats or weight loss).
How is non-Hodgkin lymphoma diagnosed?
The diagnosis of non-Hodgkin lymphoma requires an adequate biopsy of an involved lymph node or other site and evaluation by an expert hematopathologist (a specialist in the microscopic analysis of blood).
The World Health Organization classification recognizes more than two dozen distinct types of non-Hodgkin lymphoma. The specific types are defined by morphology (appearance of the malignant cells), histology (architecture of the lymph node), immunophenotype (antigen or protein expression), and genotype (specific acquired genetic abnormalities).
The distinction of the specific type of lymphoma is often crucial and helps to predict the clinical behavior and dictate management. The different types of non-Hodgkin lymphoma can be divided clinically into two categories: indolent (or "low-grade") and aggressive (or "intermediate-grade" or "high-grade"), both with subcategories:
Indolent Non-Hodgkin Lymphoma
- Follicular lymphoma (the most common type of indolent lymphoma)
- Small lymphocytic lymphoma (equivalent to chronic lymphocytic leukemia)
- Marginal zone lymphoma
- Splenic marginal zone lymphoma
- Nodal marginal zone B-cell lymphoma
- Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoma tissue (MALT)
- Lymphoplasmacytic lymphoma (associated with Waldenstrom's macroglobulinemia)
- Mycosis fungoides
- Aggressive B-Cell Non-Hodgkin Lymphoma
Diffuse large B-cell lymphoma (the most common type of aggressive lymphoma)
- Mediastinal (thymic) large B-cell lymphoma
- Intravascular large B-cell lymphoma
- Primary effusion lymphoma
- Burkitt lymphoma/leukemia
- Precursor B lymphoblastic lymphoma (equivalent to acute lymphoblastic leukemia)
- Precursor T lymphoblastic lymphoma (equivalent to acute lymphoblastic leukemia)
- Adult T-cell leukemia/lymphoma
- Blastic NK cell lymphoma
- Extranodal NK/T cell lymphoma, nasal type
- Enteropathy-type T-cell lymphoma
- Hepatosplenic T-cell lymphoma
- Subcutaneous panniculitis-like T-cell lymphoma
- Peripheral T-cell lymphoma, unspecified
- Angioimmunoblastic T-cell lymphoma
- Anaplastic large cell lymphoma
- Primary cutaneous anaplastic large cell lymphoma
- Sezary syndrome
A complete evaluation provides prognostic information and guides management. The evaluation includes a detailed history, including age, performance status, and HIV risk factors; a complete physical examination, including the size of lymph nodes, liver, and spleen; laboratory evaluation, including a various blood counts and HIV screening (if risk factors are present); imaging studies, including chest X ray, CT neck (if applicable), chest, abdomen and pelvis, and occasionally other imaging studies; bone marrow aspirate and biopsy; and infrequently, other studies, (lumbar puncture or spinal tap for cerebral spinal fluid analysis), which may identify other suspected sites of disease. Like Hodgkin lymphoma, there are four stages:
- Involvement of a single lymph node region or lymphoid structure (e.g., spleen)
- Involvement of two or more lymph node regions or lymphoid structures on the same side of the diaphragm
- Involvement of lymph node regions or lymphoid structures on both sides of the diaphragm
- Diffuse or disseminated involvement of one or more extranodal organs or tissue with or without associated lymph node involvement
Treatment of Non-Hodgkin Lymphoma
The initial management of the disease depends on the specific type of non-Hodgkin lymphoma, clinical behavior, prognostic factors, other health problems, and specific goals of therapy.
Among patients with indolent non-Hodgkin lymphoma, up to 50 percent may initially not require any treatment. In these patients, expectant monitoring of symptoms, physical findings, laboratory studies, and radiographic abnormalities is all that is required.
When patients develop symptoms (fever, night sweats, weight loss, pain or anemia), bulky tumors with impending complications, treatment is initiated. Most patients with indolent lymphoma will require a variety of different treatments over the course of many years.
Patients with localized indolent lymphoma may sometimes receive radiation therapy alone. Most patients, however, including those with advanced stage disease, are usually treated with systemic therapy.
Some patients may initially receive relatively mild treatment while others may require more intensive treatment. Rituximab, a monoclonal antibody that binds to certain cells and can kill them, is frequently administered either alone or in combination with chemotherapy. Some patients may receive 90-yttrium ibritumomab tiuxetan or 131-iodine tositumomab, (radiolabeled monoclonal antibodies), which are designed to deliver a lethal radioisotope directly to the tumor target.
Patients with Helicobacter pylori associated gastric lymphoma are frequently treated with a combination of antibiotics and antacids. Patients with small lymphocytic lymphoma are treated the same as patients with chronic lymphocytic leukemia. Some patients with indolent non-Hodgkin lymphoma are candidates for very intensive therapies (stem cell transplantation), which are also used in patients with aggressive non-Hodgkin lymphoma.
Patients with newly diagnosed, aggressive, non-Hodgkin lymphoma are treated with systemic combination therapy at the time of diagnosis. Patients with localized (stage I or II) disease may also receive radiation therapy.
The most commonly used chemotherapy regimen consists of cyclophosphamide, Doxorubicin (hydroxydaunomycin), Vincristine (oncovin), and prednisone, known as CHOP. Patients with aggressive B-cell non-Hodgkin lymphoma (diffuse large B-cell lymphoma) also receive rituximab. Patients with lymphoblastic lymphoma are treated the same as patients with acute lymphoblastic leukemia.
Patients at high risk for relapse may be offered stem cell transplantation as part of their initial treatment. Patients with progressive disease during or following initial therapy are treated with "salvage" therapy. If the lymphoma responds to this treatment, high dose therapy with stem cell transplantation may offer the best chance for long-term, disease-free survival.