Before you learn about the diagnosis of follicular lymphoma, understand follicular lymphoma.
Click here to learn about follicular lymphoma >>

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.

Key takeaways:

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

Locations of lymph nodes in the body

Locations of lymph nodes
in the body

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:

  • Fatigue
  • 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?

Example of swollen lymph nodes

Example of swollen
lymph nodes

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:

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.

The pathologistPathologist
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.

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:

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

Grading follicular lymphoma

There are three main grades describing how aggressively the lymphoma is growing:3

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

Stage I: Early Disease

Stage I: Early Disease

Lymphoma detected in one lymph node region or single localized site outside lymph nodes.3

Stage II: Locally Advanced Disease

Stage II: Locally Advanced Disease

Lymphoma detected in two or more lymph node regions situated either above or below the diaphragm.3

Stage III: Advanced Disease

Stage III: Advanced Disease

Lymphoma detected in lymph node regions situated both above and below the diaphragm.3

Stage IV: Widespread Disease

Stage IV: Widespread Disease

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.

Letter Defining Characteristics
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.

Prognosis

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.

Next section: How is Follicular Lymphoma Treated? >>

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.

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References:

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.