Before you learn about the diagnosis of follicular lymphoma, understand follicular lymphoma.
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How is Follicular Lymphoma Diagnosed?
Diagnosis is just the first step in your treatment journey, but it’s critical in planning treatment that’s right for you.
- The most common early symptom of follicular lymphoma is enlarged lymph nodesLymph Node
A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland., but many patients experience few or no lymphoma symptoms
- Doctors will conduct a physical exam and blood tests for initial screening and order different types of diagnostic tests for a complete work-up, but biopsies are the only way to confirm a lymphoma diagnosis
- Diagnostic test results help doctors determine the rate of growth (gradeGrading
A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions.) and extent (stageStage
The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.) of the lymphoma
- Doctors evaluate risk factors for follicular lymphoma patients to predict the outcome and the level of treatment the patient requires
What are early symptoms of follicular lymphoma?
Often times, early symptoms of follicular lymphoma are subtle, making them easy to miss. In addition, many people experience no obvious lymphoma symptoms at diagnosis. In that case, the disease is usually initially detected by a doctor during routine physical exams or only after the tumor becomes large enough to cause symptoms.1
The most common early symptom of follicular lymphoma is swelling of one or more lymph nodesLymph Node
A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland..1
Where are lymph nodes in the body?
Lymph nodes are located throughout the body. The figure below shows lymph node locations.
Where does lymph node swelling occur?
Lymph node swelling is usually painless and often occurs in the upper body, such as the neck or upper chest. Enlarged lymph nodes may also occur in the armpit, stomach area, or groin.2
What are other possible symptoms of follicular lymphoma?1
Other follicular lymphoma symptoms can include:
- Shortness of breath
- B symptoms
- Fever over 38oC (over 100.4oF) for 3 consecutive days
- Drenching night sweats
- Weight loss of over 10% of normal body weight (within 6 months)
Remember, experiencing these symptoms does not necessarily mean you have follicular lymphoma. Only a doctor can confirm a diagnosis of follicular lymphoma.
Most patients who experience lymphoma symptoms see a primary care physician (or another general health care practitioner) for their initial examination.
I think I have follicular lymphoma. What happens next?
If you think you have follicular lymphoma, you should visit your doctor to be screened. During the visit for initial screening, your doctor will review your medical history and perform a physical exam to:3
- Examine the size and condition of lymph nodes in several areas–under the chin, in the neck, above the shoulders, on the elbows, in the armpits, in the groin, and in the upper legs
- Examine your body for swelling or fluid in the chest or abdomen caused by swollen lymph nodes
- Examine if any internal organs are enlarged
- Ask about any pain or discomfort
- Look for any weakness or paralysis that may be caused by an enlarged lymph node pressing against nerves or the spinal cord
The doctor may also order blood tests to check for signs of lymphoma. These baseline blood tests are the first step to confirming a diagnosis when lymphoma is suspected.1
Some types of blood tests include:
- Complete Blood Count (CBC)3Complete Blood Count (CBC)
A measure of the number of red blood cells, white blood cells, and platelets in the blood. The amount of hemoglobin (substance in the blood that carries oxygen) and the hematocrit (the amount of whole blood that is made up of red blood cells) are also measured. A complete blood count is used to help diagnose and monitor many conditions. Also called blood cell count, CBC, and full blood count.
- This test measures the number of red cells, white cells, and platelets in the blood
- Having abnormal, too many, or too few of a certain type of blood cell may indicate a blood cancer
- A White Cell DifferentialWhite Cell Differential
The blood differential test measures the percentage of each type of white blood cell (WBC) that you have in your blood. It also reveals if there are any abnormal or immature cells.
- Blood Smear (or Manual Differential)2Blood Smear (or Manual Differential)
A blood smear is a diagnostic test used to look for abnormalities within the blood. The cell types are examined under a microscope for unusual shapes or sizes.
- This test gives information about the number and the shape of red cells, white cells, and platelets in the blood
- Irregularities in the size and shape of these cells may indicate a blood cancer or other underlying conditions
- Blood smears may be ordered to gain further information following an abnormal CBC
- Blood Chemistry (or Chemistry Panel)1,2Blood Chemistry
A procedure in which a sample of blood is examined to measure the amounts of certain substances made in the body. An abnormal amount of a substance can be a sign of disease in the organ or tissue that produces it.
- This test measures levels of naturally occurring chemicals in the blood
- Test results provide information about the patient’s overall health and bodily functions
Based on the results of your initial physical exam and blood tests, your doctor may suspect that you have lymphoma. If that’s the case, further exams will be conducted to confirm the diagnosis.1
What is a biopsy?3
While many exams may be ordered, it’s important to know that only a biopsy can definitively confirm a diagnosis of follicular lymphoma.1
A biopsy is a procedure in which a surgeon removes a piece of tissue from an area of suspected disease, such as an affected lymph node or a tumorTumor
An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.. The tissue removed will be given to another specialist (a pathologist) for further examination.
A doctor who identifies diseases by studying cells and tissues under a microscope. will look at the tissue under a microscope and make a diagnosis. The information provided by this tissue sample is crucial to doctors in correctly diagnosing the disease and deciding on the best course of cancer treatment.
There are two main types of biopsies that doctors use for patients with lymphoma–your doctor will determine the right one for you.
- Excisional or Incisional BiopsyExcisional/Incisional biopsy
A surgical procedure in which an entire/portion of a lump or suspicious area is removed for diagnosis. The tissue is then examined under a microscope to check for signs of disease.
- A surgeon cuts through the skin to remove a full lymph node (excisional) or a portion of the lymph node tissue (incisional)
- These biopsies are best for establishing an initial diagnosis because the procedures allow for extraction of larger samples than other biopsies. Larger samples mean that there is enough sample to diagnose the exact type of lymphoma.
- Core/Fine Needle AspirationCore/Fine needle aspiration
The removal of tissue or fluid with a thin needle for examination under a microscope. Also called FNA biopsy.
- A surgeon inserts a needle into a lymph node to extract a small tissue sample
- This type of biopsy is used when lymph nodes are deeper in the body and are more difficult to reach, or if there are medical reasons for avoiding an excisional or incisional biopsy
Doctors may also order other tests to further inform the diagnosis
Making a follicular lymphoma diagnosis is complex. For that reason, patients diagnosed with follicular lymphoma should consider getting a second opinion to confirm biopsy results.
Additional tests may include:
- Imaging tests1
- Chest X-ray
- This test shows enlarged lymph nodes in the chest and neck area
- Computed Tomography (CT) Scan
- This test is an advanced type of X-ray that provides detailed pictures of the body
- CT scans of the chest, head, neck, abdomen and pelvis can detect abnormalities and help with the staging of the disease
- Magnetic Resonance Imaging (MRI) ScanMagnetic Resonance Imaging (MRI) Scan
A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. MRI makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or x-ray. MRI is especially useful for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. Also called magnetic resonance imaging, NMRI, and nuclear magnetic resonance imaging.
- This test uses magnetic waves to take detailed pictures of the body
- MRIs may be used to detect the spread of the disease to the chest, pelvis, abdomen, brain, or spinal chord
A procedure that uses high-energy sound waves to look at tissues and organs inside the body. The sound waves make echoes that form pictures of the tissues and organs on a computer screen (sonogram). Ultrasound may be used to help diagnose diseases, such as cancer. It may also be used during pregnancy to check the fetus (unborn baby) and during medical procedures, such as biopsies. Also called ultrasonography.
- This test uses sound waves to generate an image of the inside of the body
- Ultrasounds are typically used to find tumors in the abdomen and to see if kidneys have been affected by swollen lymph nodes
- Positron Emission Tomography (PET) ScanPositron Emission Tomography (PET) Scan
A procedure in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is taken up. Because cancer cells often take up more glucose than normal cells, the pictures can be used to find cancer cells in the body. Also called positron emission tomography scan.
- This test detects metabolic activityMetabolic Activity
Having to do with metabolism (the total of all chemical changes that take place in a cell or an organism to produce energy and basic materials needed for important life processes). in the body
- PET scans involve an injection of a sugar and radioactive tracerRadioactive Tracer
A substance (such as a radioisotope) used in imaging procedures., which gets taken up by cancer cells. Special PET cameras then detect the location of the mixtures and where the cancer is in the body
- This test detects metabolic activityMetabolic Activity
- Chest X-ray
A process used to identify cells, based on the types of antigens or markers on the surface of the cell. This process is used to diagnose specific types of leukemia and lymphoma by comparing the cancer cells to normal cells of the immune system. or ImmunohistochemistryImmunohistochemistry
A laboratory test that uses antibodies to test for certain antigens in a sample of tissue. The antibody is usually linked to a radioactive substance or a dye that causes the antigens in the tissue to light up under a microscope. Immunohistochemistry is used to help diagnose diseases, such as cancer. It may also be used to help tell the difference between different types of cancer.
- This test distinguishes different types of non-Hodgkin’s lymphoma from one another and from other diseases
- Immunohistochemistry involves the use of special antibodiesAntibody
A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. An antibody is a type of immunoglobulin. to detect and color different molecules on the surface of lymphoma cells
- This process is conducted during evaluation of biopsy material
The study of chromosomes and chromosomal abnormalities.
- This test identifies the type of lymphoma
- Cytogenetics involves the analysis of lymphoma cell chromosomesChromosome
Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. (DNA strands) to find abnormalities
- Molecular Genetics TestsMolecular Genetics Tests
Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder.
- This test identifies what genes are active, or “on”, in the lymphoma
- Additional biopsies
- Bone Marrow AspirationBone Marrow Aspiration
A procedure in which a small sample of bone marrow is removed, usually from the hip bone, breastbone, or thigh bone. A small area of skin and the surface of the bone underneath are numbed with an anesthetic. Then, a special wide needle is pushed into the bone. A sample of liquid bone marrow is removed with a syringe attached to the needle. The bone marrow is sent to a laboratory to be looked at under a microscope. This procedure may be done at the same time as a bone marrow biopsy. and Biopsy
- This test determines whether the lymphoma has spread to the bone marrow
- A surgeon inserts a needle into the hip bone to remove a small amount of bone marrow for analysis
- Lumbar Puncture (or Spinal Tap)Lumbar Puncture (or Spinal Tap)
A procedure in which a thin needle called a spinal needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give drugs. Also called spinal tap.
- This test looks for lymphoma cells in the Cerebrospinal fluidLumbar Puncture (or Spinal Tap)
The fluid that flows in and around the hollow spaces of the brain and spinal cord, and between two of the meninges (the thin layers of tissue that cover and protect the brain and spinal cord). Cerebrospinal fluid is made by tissue called the choroid plexus in the ventricles (hollow spaces) in the brain. Also called CSF.—the liquid that surrounds the brain and spinal chord
- A doctor or surgeon inserts a needle between the bones of the spine to withdraw fluid
- Lumbar punctures may be ordered particularly if doctors suspect the lymphoma has spread to the brain
- This test looks for lymphoma cells in the Cerebrospinal fluidLumbar Puncture (or Spinal Tap)
- Bone Marrow AspirationBone Marrow Aspiration
- Heart and lung function tests
What happens after diagnosis?
Once a diagnosis of follicular lymphoma is made, it is important to determine how far the disease has progressedProgressed/Progression
In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.. This will help determine the cancer treatment options and prognosis. Lymphoma progression is measured in two ways:3
A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions.: How aggressively the lymphoma may have grown and developed
The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.: The extent the lymphoma has spread throughout the body
Grading follicular lymphoma
There are three main grades describing how aggressively the lymphoma is growing:3
- Low-grade (indolentIndolent
A type of cancer that grows slowly.): Grows and spreads slowly, with fewer lymphoma symptoms
- Intermediate-grade (aggressiveAggressive
In medicine, describes a tumor or disease that forms, grows, or spreads quickly. It may also describe treatment that is more severe or intense than usual.A type of lymphoma that grows and spreads quickly and has severe symptoms; also known as high-grade or intermediate-grade. ): Grows and spreads quickly, with more severe lymphoma symptoms
- High-grade (highly aggressive): Grows and spreads very quickly, with more severe lymphoma symptoms
All follicular lymphomas start as indolent or low-grade lymphomas.
Staging follicular lymphoma
Determining how far the lymphoma has spread is an important factor in deciding what cancer treatment approach to use. All lymphomas are staged using a scale known as the Ann Arbor Staging System.1,3
This system uses the diaphragm as a point of reference and division line for recognizing the location of affected lymph nodes.3
Lymphoma detected in one lymph node region or single localized site outside lymph nodes.3
Lymphoma detected in two or more lymph node regions situated either above or below the diaphragm.3
Lymphoma detected in lymph node regions situated both above and below the diaphragm.3
Lymphoma detected in one or more organs with or without lymph node involvement.3
In addition to the stage numbers, doctors may further classify the lymphoma by assigning letters to the stage. Non-Hodgkin’s lymphoma staging includes the use of “A” or “B” to describe the disease. This is based on whether the patient has any of the B symptoms. “A” means those symptoms are not present. “B” means the patient has experienced fevers, night sweats, or weight loss. For example, a Stage II patient with these symptoms would be described as Stage IIB. An additional modifier used to describe lymphoma is X. It is added if the largest tumor is greater than 10cm in size.
|A||Patient has not experienced lymphoma symptoms, such as fevers, night sweats, or significant weight loss (more than 10% in 6 months)|
|B||Patient exhibits B symptoms–has experienced fevers, night sweats, or has lost weight (more than 10% in 6 months)|
|X||Patient has “bulky” disease–the largest lymphoma tumor is greater than 10cm or 4in wide|
Because symptoms of follicular lymphoma are subtle and often painless, warning signs are often missed. As a result, a majority of follicular lymphoma patients are in an advanced stage by the time they are diagnosed.
The diagnosis, stage, and grade of the disease inform doctors of the current state of the disease. Doctors then need to determine what will happen next–in other words, the prognosis.
The term “prognosis” means the likely outcome of the disease, like the length of time before a person’s lymphoma progresses after diagnosis and/or treatment. Prognosis is often confused with clinical aggressiveness of the disease, but they are not the same thing. Non-Hodgkin’s lymphoma prognosis does not necessarily correlate with the aggressiveness of the disease.3
Patients with follicular lymphoma are often evaluated for different risk factors that may predict prognosis. Ask your doctor more about which risk factors you may have and how they affect your prognosis.
Indications and Usage
ZEVALIN® (ibritumomab tiuxetan) injection for intravenous use is a prescription medication that has three parts: two infusions of rituximab and one injection of Yttrium-90 (Y-90) ZEVALIN. Rituximab is used to reduce the number of B-cells in your blood and Y-90 ZEVALIN is given to treat your non-Hodgkin's lymphoma (NHL).
The ZEVALIN therapeutic regimen is used to treat patients with:
- Low-grade or follicular B-cell NHL that has relapsed during or after treatment with other anticancer drugs.
- Newly diagnosed follicular NHL following a response to initial anticancer therapy.
Patient Important Safety Information
What Is the Most Important Safety Information I Should Know About ZEVALIN Treatment?
The following section provides an overview of the most important safety information you should know about ZEVALIN, including side effects. Not all of the safety information about ZEVALIN treatment is included here. For complete safety information, please see the accompanying full prescribing information for ZEVALIN. Additional information may also be found on the ZEVALIN Website (www.ZEVALIN.com) or by speaking with your health care provider. Because ZEVALIN treatment includes the use of rituximab, please see the rituximab medication guide (www.rituxan.com).
WARNING: ZEVALIN TREATMENT CAN CAUSE SERIOUS SIDE EFFECTS:
- Serious Infusion Reactions: Rituximab, alone or as part of the ZEVALIN treatment, may cause serious infusion reactions. Deaths have occurred within 24 hours of rituximab infusion, an important component of the ZEVALIN treatment. Tell your doctor or infusion nurse or get medical treatment right away if you develop fever or chills, a rash, itching, dizziness, swelling of your hands, feet or face, throat irritation or trouble breathing during or after receiving the ZEVALIN treatment.
- Extended and Severe Decreases in Your Blood Counts (Cytopenias): Your doctor will monitor your blood counts after receiving the ZEVALIN treatment. Decreased blood counts can occur late and continue for more than 12 weeks after receiving ZEVALIN. Tell your doctor if you have a fever, feel too tired to do daily activities, feel weak, develop bruises or pinpoint red or purple spots on your skin, have unusual bleeding or notice blood in your urine or stool.
- Severe Skin or Mucous Membrane Reactions: If you experience any reactions related to your skin or mucous membranes (e.g. mouth, nose), your infusion of rituximab and Y-90 ZEVALIN should be discontinued.
Dosing Warning: The dose of Y-90 ZEVALIN should not exceed 32.0 mCi (1184 MBq).
Additional Safety Information:
Risk of Developing Myelodysplastic Syndrome, Leukemia and Other Malignancies (Cancers): The radiation dose resulting from therapeutic exposure to Y-90 ZEVALIN may result in secondary malignancies.
Myelodysplastic syndrome (MDS; a type of pre-cancerous bone marrow abnormality) and/or Acute Myelogenous Leukemia (AML, a type of cancer of the blood) were reported in 5.2% (11/211) of patients treated with Y-90 ZEVALIN for relapsed or refractory non-Hodgkin's lymphoma (NHL) in clinical studies, and 1.5% (8/535) of all patients included in the expanded-access trial, with median follow-up of 6.5 and 4.4 years, respectively. Among the 19 reported cases, the median time to diagnosis of MDS or AML was 1.9 years following the ZEVALIN therapy; however, the total incidence continues to increase.
Among 204 newly diagnosed patients who received Y-90 ZEVALIN, following complete or partial response to initial anticancer therapy, 7 patients (3.4%) were diagnosed with MDS/AML after receiving ZEVALIN treatment, compared to one patient (0.5%, 1/205) in the control arm, with a median follow-up of 7.3 years. Deaths due to secondary new malignancies occurred in 8 (3.9%) patients treated with ZEVALIN compared to 3 (1.5%) patients in the control arm of the study. Deaths due to MDS or AML occurred in 5 (2.5%) patients treated with ZEVALIN compared to no patients in the control arm.
- Infusion Site Leakage: ZEVALIN may leak from your vein or infusion site. Your doctor will monitor you during treatment and will stop the infusion and switch to another vein, if this occurs during treatment.
- Immunization: Do not get a vaccine that contains live virus for at least 12 months following ZEVALIN treatment.
- Precautions During and After Administration: Your doctor will discuss precautions with you to minimize radiation exposure.
- Potential for Birth Defects: ZEVALIN therapy may cause harm to an unborn baby, please tell your doctor if you are pregnant or plan to become pregnant.
- Reproductive Organs: There is a risk that ZEVALIN therapy will affect the male and female reproductive organs. Use birth control during treatment and for a minimum of 12 months following ZEVALIN therapy.
- Nursing Mothers: Discontinue nursing during and after ZEVALIN treatment.
Adverse Reactions (Side Effects): The most common adverse reactions (≥10%) in clinical trials with ZEVALIN were: decreases in blood counts, tiredness, inflammation of the nose and upper throat, nausea (upset stomach), abdominal (stomach) pain, weakness, cough, diarrhea, and fever. The most serious adverse reactions of ZEVALIN are prolonged and severe reduction in the number of blood counts and secondary cancers.
When administered following initial anticancer therapy, grade 3/4 adverse reactions of ZEVALIN include prolonged and severe decrease in blood counts (decrease in platelets [51%], decrease in neutrophils (a type of white blood cell) [41%], decrease in total white blood cells [36%], decrease in lymphocytes [18%], and decrease in red blood cells or hemoglobin [5%]), and secondary cancers (12.7%). Reductions in blood cells were more severe and more prolonged among 11 (5%) patients who received ZEVALIN after first-line fludarabine or a fludarabine-containing anticancer regimen as compared to patients receiving non-fludarabine-containing regimens. Grade 3/4 infections occurred in 8% of ZEVALIN-treated patients and in 2% of controls and included neutropenic sepsis (fever and infection due to decrease in the number of neutrophils [1%]), bronchitis, catheter sepsis (bacterial infection in the blood related to catheter), diverticulitis (inflammation in the intestines), shingles or blistering skin rash caused from herpes virus reactivation, flu, lower air passage infection, sinusitis (swelling of the sinuses), and upper air passage infection.
Grade 3/4 adverse reactions of ZEVALIN in recurring NHL patients include prolonged and severe reduction of blood cells (decrease in platelets [63%], decrease in neutrophils [60%], decrease in red blood cells or hemoglobin [17%], and ecchymosis (small blue or purple patch on the skin or mucous membrane [<1%])) and secondary cancers (5.2%). Serious infections occurred in 3% of patients (urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis (type of skin infection), colitis (swelling of the large intestine), diarrhea, osteomyelitis (bone infection), and upper-air passage infection). Life-threatening infections were reported in 2% of patients (sepsis, empyema (collection of pus in a cavity in the body), pneumonia, febrile neutropenia, fever, and biliary stent-associated cholangitis (bile duct infection)).
Please click here to see the full Prescribing Information, including the BOXED WARNINGS, for ZEVALIN. Because ZEVALIN treatment includes the use of rituximab, please see the rituximab medication guide (www.rituxan.com).
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
1. Non-Hodgkin Lymphoma Overview. American Cancer Society Web site. http://www.cancer.org/acs/groups/cid/documents/webcontent/003067-pdf.pdf. Updated January 28, 2015. Accessed March 13, 2015.
2. Adult Non-Hodgkin Lymphoma Treatment (PDQ®). National Cancer Institute Web site. http://www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/Patient/page1/print. Updated April 25, 2014. Accessed March 13, 2015.
3. Understanding Non-Hodgkin Lymphoma. Lymphoma Research Foundation Web site. http://www.lymphoma.org/atf/cf/%7Baaf3b4e5-2c43-404c-afe5-fd903c87b254%7D/LRF%20UNDERSTANDING%20NHL%20GUIDE2.PDF. Updated 2012. Accessed March 13, 2015.