What is Follicular Lymphoma?

Follicular pattern -- collection of ovals -- as seen in a mammalian lymph node in cross section using light microscopy.

Lymphoma is a cancer that affects the lymphocytes, a kind of cell located in the blood, in the bone marrow, and in the lymph nodes.

Follicular Lymphoma, or FL

FL is the most common type of indolent -- that is, slow growing -- lymphoma, but slow growing cells have the potential to transform into something more aggressive.

-- FL is a non-Hodgkin's Lymphoma, or NHL

The two main kinds of lymphoma are Hodgkin’s lymphoma and non-Hodgkin’s lymphoma, or NHL.

Follicular lymphoma is a non-Hodgkin's lymphoma. Non-Hodgkin lymphomas arise from the cells of the immune system -- B cells, T cells, and natural killer cells. In most of the cases, the cancer cells are located in the lymph nodes or in other lymphoid tissues -- such as the spleen and bone marrow -- but they may also invade other organs such as the small bowel and kidney.

-- FL is a B-cell Lymphoma

Most kinds of NHL -- about 90 percent -- are of B-cell origin.

Like most non-Hodgkin lymphomas, FL is of B-cell origin.

-- FL is a Mature B-cell Lymphoma

Another way to group lymphomas is by the maturity of the cells that give rise to the malignancy – that is, separating lymphomas that arise from immature, “precursor lymphocytes” from those derived from “mature lymphocytes.” FL is derived from mature B lymphocytes. Diffuse large B-cell lymphoma, or DLBCL, is another example of a mature B-cell malignancy.

FL can transform into DLBCL.

FL is Common

FL and DLBCL together account for about 50 percent of lymphomas in the U.S.

FL is the second most common lymphoma, behind DLBCL:

  • DLBCL -- About 1 out of every 3 NHL
  • FL -- About 1 in 5 lymphomas

FL has Subtypes

According to the 2015 guidelines from the National Comprehensive Cancer Network, or NCCN, follicular lymphoma can be further classified into the following subtypes:

-- Extranodal FL -- Primary intestinal and Other extranodal

-- Follicular Lymphoma “in situ”

-- Primary Cutaneous Follicle Center Lymphoma, or PC-FCL*

-- Pediatric-type FL, which is a rare form.

*Lymphomas of the PC-FCL type tend to develop and stay mostly in the skin. Because the diagnosis, behavior, and treatment of this type of FL differ significantly from the other follicular lymphomas, PC-FCL is not discussed in depth here.

Symptoms

  • Most people who are diagnosed with FL have painless swelling in one or more lymph nodes.
  • Besides lymph node swelling, many patients do not have other symptoms when they are first diagnosed. “B symptoms” such as fever and weight loss are relatively rare.

Risk Factors

  • Follicular lymphoma is not an inherited disease. If someone in your family is diagnosed with follicular lymphoma, your risk of developing FL is not much greater than that of an unrelated individual.
  • Follicular lymphoma may be less common in Asians and Blacks than other races.
  • The average age at diagnosis is 65 years. Most individuals diagnosed with FL are adults. By comparison, pediatric type follicular lymphoma is rare.

    Diagnosis

    A diagnosis of follicular lymphoma is confirmed by testing a sample of the enlarged lymph node to look at its cells under a microscope. This procedure is called a lymph node biopsy. Other diagnostic tests and evaluations are done from there, as needed, potentially including the search for markers.

    Staging

    A variety of tests may be done for the purposes of staging, including:

    • Blood tests
    • Bone marrow biopsy -- taking a small sample of tissue from the bone marrow
    • Computed tomography, or CT scan
    • Positron emission tomography, or PET, scan

    Staging refers to the extent of spread. Different staging systems have been in use, but here is one commonly used system that has four stages:

    • Stage I – Only one lymph node region is involved, or only one structure is involved.
    • Stage II – Two or more lymph node regions or structures on the same side of the diaphragm are involved.
    • Stage III – Lymph node regions or structures on both sides of the diaphragm are involved.
    • Stage IV – There is widespread involvement of a number of organs or tissues other than lymph node regions or structures, such as the bone marrow.

    About 15 to 20 percent of people with FL have stage II or I disease at diagnosis.

    Over 40 percent have stage IV disease at diagnosis.

    Grading refers to how aggressive the FL appears to be based on microscopic characteristics. Grades 1, 2 and 3 are possible, with grade 3 being the most controversial in terms of what it means for the outcome.

    Treatment

    Oftentimes, FL is slow-growing and lacks aggressive characteristics. Both the decision to treat as well as the first-line treatment of choice may be influenced by a number of factors, including candidacy for clinical trials, overall health, and presentation of the disease. Specific preferred treatments may vary for different individuals and for different forms of FL.

    According to the 2015 NCCN guidelines, observation -- rather than treatment -- may be appropriate in certain circumstances. When treatment is pursued, with regard to first-choice treatment, NCCN guidelines include a variety of options for different situations. Use of bendamustine plus rituximab is one such option. Treating doctors may suggest alternatives for first-choice therapy based on expectations regarding how well a person might be expected to tolerate a given therapy.

    Prognosis

    The Follicular Lymphoma International Prognostic Index, or FLIPI has been used to score risk from disease. Blood tests, the type of FL and a person's age and overall health are all relevant factors in assessing risk and prognosis.

    Pediatric-type FL has a better prognosis than adult FL and is often cured with minimal therapy. Most patients with primary intestinal follicular lymphoma have slow-growing and localized disease, and survival appears to be excellent even without treatment. PC-FCL has a 5-year survival rate of 95 percent.

    Sources

    NCCN Clinical Practice Guidelines in Oncology. Version 2.2015.

    Leibel and Phillips Textbook of Radiation Oncology: Expert Consult; Hoppe R, et al.

    Trotman J, Fournier M, Lamy T, et al. Positron emission tomography-computed tomography (PET-CT) after induction therapy is highly predictive of patient outcome in follicular lymphoma: analysis of PET-CT in a subset of PRIMA trial participants. J Clin Oncol 2011;29:3194-3200.

    Lymphoma: Pathology, Diagnosis, and Treatment. 2013; Robert Marcus, et al.

    Flinn IW, van der Jagt R, Kahl BS, et al. Open-label, randomized, noninferiority study of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of advanced indolent NHL or MCL: the BRIGHT study. Blood 2014;123:2944-2952.

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