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Medical Author:

Jerry R. Balentine, DO, FACEP

Jerry R. Balentine, DO, FACEP

Dr. Balentine received his undergraduate degree from McDaniel College in Westminster, Maryland. He attended medical school at the Philadelphia College of Osteopathic Medicine graduating in1983. He completed his internship at St. Joseph's Hospital in Philadelphia and his Emergency Medicine residency at Lincoln Medical and Mental Health Center in the Bronx, where he served as chief resident.

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Medical Editor:

Melissa Conrad Stöppler, MD, Chief Medical Editor

Melissa Conrad Stöppler, MD, Chief Medical Editor

Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

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Lymphoma Diagnosis

If a person has swelling or symptoms described in the Symptoms section, his or her health-care provider will ask many questions about the symptoms (when they began, recent illnesses, past or current medical problems, any medications, workplace, health history, family history, and habits and lifestyle). These questions are followed by a thorough examination.

If, after an initial interview and examination, the health-care provider suspects that a patient may have lymphoma, the patient will undergo a series of tests designed to provide further clarification. At some point in this workup, the patient will likely be referred to a specialist in blood diseases and cancer (hematologist/oncologist).

Blood tests

Blood is drawn for various tests.

• Some of these tests evaluate the function and performance of blood cells and important organs, such as the liver and kidneys.



• Certain blood chemicals or enzymes (lactate dehydrogenase [LDH]) may be determined. High levels of LDH in cases in which NHL is suspected may indicate a more aggressive form of the disorder.



• Other tests may be done to learn more about lymphoma subtypes.

Biopsy

If there is a swelling (also called lump or mass), a sample of tissue from the swelling will be removed for examination by a pathologist. This is called a biopsy. Any of several methods can be used to obtain a biopsy of a mass.

• Masses that can be seen and felt under the skin are relatively easy to biopsy. A hollow needle can be inserted into the mass and a small sample removed with the needle (called a core-needle biopsy). This is usually done in the health-care provider's office with a local anesthetic.



• Core-needle biopsy does not always obtain a good-quality sample. For that reason, many health-care providers prefer a surgical biopsy. This involves removal of the entire swollen lymph node through a small incision in the skin. This procedure often is done with a local anesthetic, but it sometimes requires a general anesthetic.



• If the mass is not immediately under the skin but is instead deep inside the body, access is somewhat more complicated. The tissue sample is usually obtained via laparoscopy. This means making a tiny incision in the skin and inserting a thin tube with a light and a camera on the end (a laparoscope). The camera sends pictures of the inside of the body to a video monitor, and the surgeon can see the mass. A small cutting tool on the end of the laparoscope can remove all or part of the mass. This tissue is withdrawn from the body with the laparoscope.



• A pathologist (a physician who specializes in diagnosing diseases by looking at cells and tissues) examines the tissue sample with a microscope. The pathologist's report will specify whether the tissue is lymphoma and the type and subset of lymphoma.

Imaging studies

If there is no palpable mass in the presence of persistent symptoms, imaging studies will likely be carried out in order to determine whether a mass is present and, if so, how then to direct a biopsy.

• X-rays: In certain parts of the body, such as the chest, a simple X-ray can sometimes detect lymphoma.



• CT scan: This test provides a three-dimensional view and much greater detail and may detect enlarged lymph nodes and other masses anywhere in the body.



• MRI scan: Similar to the CT scan, MRI gives three-dimensional images with excellent detail. MRI provides better definition than CT scan in certain parts of the body, especially the brain and the spinal cord.



• Lymphangiogram: This approach, which provides an image of the lymphatic system by tracing a dye that moves though the system, has essentially been replaced by either CT scan, MRI, or PET (see below).



• Gallium scan: Lymphomas tend to collect a substance called gallium when injected into the body. For this test, a tiny amount of radioactive gallium is injected into the body. A scan is then done to find areas where the gallium has collected. Collections of gallium suggest a tumor.



• Positron-emission tomographic (PET) scan: PET scan is a newer alternative to lymphangiogram and gallium scan for detecting areas in the body that are affected by lymphoma. A tiny amount of a radioactive substance is injected into the body and then traced on the PET scan. Sites of radioactivity on the scan indicate areas of increased metabolic activity, which implies the presence of a tumor.

Bone marrow examination

Most of the time, an examination of the bone marrow is necessary to see if the marrow is affected by the lymphoma. This is done by collecting a biopsy of the bone marrow.

• Samples are taken, usually from a hip bone.



• A pathologist examines the bone marrow under a microscope.



• Bone marrow containing certain types of abnormal B or T lymphocytes confirms lymphoma.



• Bone marrow biopsy can be an uncomfortable procedure, but it can usually be performed in a medical office. Most people receive pain medication prior to the procedure to make them more comfortable.

Other tests

• Lumbar puncture: This test, sometimes called a spinal tap, is a method for collecting a sample of the fluid surrounding the brain and spinal cord. This fluid is called cerebrospinal fluid. If the lymphoma has affected the central nervous system, the cerebrospinal fluid will likely contain lymphoma cells.



• Organ function tests: These tests are usually done before starting treatment to make sure that one's organs are healthy enough to withstand the side effects of therapy. Examples include an echocardiogram or MUGA scan (a test that provides a movie-like image of the working heart) for the heart and pulmonary function tests for the lungs.

Staging

Staging is the classification of a cancer type by its size and whether and how much it has spread around the body. Determining a cancer's stage is very important because it tells the oncologist which treatment is most likely to work and what are the chances of remission or a cure (prognosis).

Staging of lymphomas is based on the results of imaging studies and related tests that reveal the extent of the cancer involvement.

HL is often described as being "bulky" or "nonbulky." Nonbulky means the tumor is small; bulky means the tumor is large. Nonbulky disease has a better prognosis than bulky disease.

NHL is a complicated set of diseases with a complex classification system. In fact, the classification system is continuously evolving as we learn more about these cancers. The newest classification system takes into account not only the microscopic appearance of the lymphoma but also its location in the body and genetic and molecular features.

Grade is also an important component of the NHL classification.

• Low grade: These are often called "indolent" lymphomas because they grow slowly. Low-grade lymphomas are often widespread when discovered, but because they grow slowly, they usually do not require immediate treatment unless organ function is compromised. They are rarely cured and can transform over time to a combination of indolent and aggressive types.



• Intermediate grade: These are rapidly growing (aggressive) lymphomas that usually require immediate treatment, but they are often curable.



• High grade: These are very rapidly growing and aggressive lymphomas that require immediate, intensive treatment and are much less often curable.

The "staging," or evaluation of extent of disease, for both HL and NHL, are similar.

• Stage I (early disease): Lymphoma is located in a single lymph node region or in one area or organ outside the lymph node.



• Stage II (locally advanced disease): Lymphoma is located in two or more lymph node regions all located on the same side of the diaphragm or in one lymph node region and a nearby tissue or organ. (The diaphragm is a flat muscle that separates the chest from the abdomen.)



• Stage III (advanced disease): Lymphoma affects two or more lymph node regions, or one lymph node region and one organ, on opposite sides of the diaphragm.



• Stage IV (widespread or disseminated disease): Lymphoma is outside the lymph nodes and spleen and has spread to another area or organ such as the bone marrow, bone, or central nervous system.

Both HL and NHL are further classified with letters.

• An "A" or "B" designation indicates whether the person with lymphoma had symptoms such as fevers and/or weight loss at the time of diagnosis. "A" indicates no such symptoms, and "B" indicates symptoms.



• An "E" designation indicates that the tumor spread directly from a lymph node into an organ or that a single organ outside the lymphatic system is affected with no apparent lymphatic involvement. If the spleen is involved an "S" designation is added.

Prognostic factors

Several risk factors have been extensively evaluated and shown to play a role in treatment outcome. For HL, the International Prognostic Index includes the following seven risk factors:

1. Male sex



2. Age 45 years or older



3. Stage IV disease



4. Albumin (blood test) less then 4.0 g/dL



5. Hemoglobin (red blood cell level) less than 10.5 g/dL



6. Elevated white blood cell (WBC) count of 15,000/mL



7. Low lymphocyte count less than 600/mL or less than 8% of total WBC

The absence of any of the above risk factors is associated with an 84% rate of control of Hodgkin's disease, whereas the presence of a risk factor is associated with a 77% rate of disease control. The presence of five or more risk factors was associated with a disease control rate of only 42%.

The outcomes for these patients were also determined by the treatment they received, which occurred primarily in the 1980s. Newer treatments for Hodgkin's lymphoma may improve these predicted outcomes. Furthermore, new treatments are being developed for patients with greater risk factors.

The International Prognostic Index for NHL includes five risk factors:

1. Age older than 60 years



2. Stage III or IV disease



3. High LDH



4. More than one extranodal site



5. Poor performance status (as a measure of general health): From these factors, the following risk groups were identified:

• Low risk: one risk factor, five-year lymphoma-free survival (LFS) of 70%



• Intermediate risk: two to three risk factors, five-year LFS of 49%-50%



• Poor risk: four to five risk factors, five-year LFS of 26%

The prognostic models were developed to evaluate groups of patients and are useful in developing therapeutic strategies. It is important to remember that any individual patient might have significantly different results than the above data, which represent statistical results for a patient group.