Follicular lymphoma is the most common of the indolent non-Hodgkin's lymphomas, and the second most common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma

Lymphoma

Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...

 of follicle center B-cells (centrocytes and centroblasts), which has at least a partially follicular pattern. It is positive for the B-cell markers CD10, CD19, CD20, and CD22 but almost always negative for CD5

CD5 (protein)

CD5 is a cluster of differentiation found on a subset of IgM-secreting B cells called B-1 cells, and also on T cells. B-1 cells have limited diversity of their B-cell receptor due to their lack of the enzyme terminal deoxynucleotidyl transferase and are potentially self-reactive...

.

There are several synonymous and obsolete terms for this disease, such as CB/CC lymphoma (Centroblastic and Centrocytic lymphoma), nodular lymphoma and Brill-Symmers Disease.

Morphology

The tumor

Tumor

A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 is composed of follicles containing a mixture of centrocyte

Centrocyte

A centrocyte generally refers to a B cell with a cleaved nucleus, as may appear in e.g. follicular lymphoma.It can also refer to a cell with a protoplasm that contains single and double granules of varying size stainable with hematoxylin, as seen in lesions of lichen planus, or a nondividing,...

s (WHO nomenclature) or cleaved follicle center cells (older American nomenclature), "small cells

Small Cells

Small Cells are low-powered radio access nodes that operate in licensed and unlicensed spectrum that have a range of 10 meter to 200 meters, compared to a mobile Macrocell which might have a range of a few kilometres. With mobile operators struggling to support the growth in mobile data traffic,...

", and centroblasts (WHO nomenclature) or large noncleaved follicle center cells (older American nomenclature), "large cells". These follicles are surrounded by non-malignant cells, mostly T-cells. In the follicles, centrocytes typically predominate; centroblasts are usually in minority.

Grading

According to the WHO criteria, the disease is morphologically graded into:

• grade 1 (<5 centroblasts per high-power field (hpf))
• grade 2 (6–15 centroblasts/hpf)
• grade 3 (>15 centroblasts/hpf).

Grade 3 is further subdivided into:

• • grade 3A (centrocytes still present)
  • grade 3B (the follicles consist almost entirely of centroblasts)

The clinical relevance of this grading system is still being debated; Grades 1, 2, and 3A are considered to be indolent and incurable while grade 3B is considered an aggressive but curable disease similar to diffuse large B-cell lymphoma. Occasional cases may show plasmacytoid differentiation or foci of marginal zone

Marginal zone

The marginal zone is the region at the interface between the non-lymphoid red pulp and the lymphoid white-pulp of the spleen. A marginal zone also exists in lymph nodes.-Composition and markers:It is composed of cells derived...

 or monocytoid B-cells.

Causes

A translocation

Chromosomal translocation

In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...

 between chromosome

Chromosome

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 14 and 18 results in the overexpression of the bcl-2

Bcl-2

Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...

 gene. As the bcl-2 protein is normally involved in preventing apoptosis

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

, cells with an overexpression of this protein are basically immortal. The bcl-2 gene is normally found on chromosome 18, and the translocation moves the gene near to the site of the immunoglobulin heavy chain enhancer element on chromosome 14.

Translocations of BCL6

BCL6

B-cell lymphoma 6 protein is a protein that in humans is encoded by the BCL6 gene.- Function :The protein encoded by this gene is an evolutionarily conserved zinc finger transcription factor and contains an N-terminal POZ/BTB domain...

 at 3q27 can also be involved.

Treatment

There is no consensus regarding the best treatment protocol. Several considerations should be taken into account including age, stage and prognostic scores. Patients with advanced disease who are asymptomatic might benefit of a watch and wait approach as early treatment does not provide survival benefit. When patients are symptomatic, specific treatment is required which might include various combinations of alkylators, nucleoside analogues, anthracycline-containing regimens (e.g. CHOP

CHOP

CHOP is the acronym for a chemotherapy regimen used in the treatment of non-Hodgkin lymphoma. CHOP consists of:* Cyclophosphamide, an alkylating agent which damages DNA by binding to it and causing cross-links...

) monoclonal antibodies (rituximab), radioimmunotherapy, autologous and allogeneic hematopoietic stem cell transplantation. The disease is regarded as incurable (although allogeneic stem cell transplantation may be curative, the mortality

Death

Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

 from the procedure is too high to be a first line option). The exception is localized disease, which can be cured by local irradiation

Irradiation

Irradiation is the process by which an object is exposed to radiation. The exposure can originate from various sources, including natural sources. Most frequently the term refers to ionizing radiation, and to a level of radiation that will serve a specific purpose, rather than radiation exposure to...

.

Personalised idiotype vaccines have shown great promise, but has still to prove its efficacy in randomized clinical trials.

In 2010 Rituximab

Rituximab

Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...

 was approved by the EC for first-line maintenance treatment of follicular lymphoma.

There are a large number of recent and current clinical trials for FL.

Prognosis

Median

Median

In probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...

 survival is around 10 years, but the range is wide, from less than one year, to more than 20 years. Some patients may never need treatment. The overall survival rate at 5 years is 72-77%.

Epidemiology

Of all cancers involving the same class of blood cell

Lymphoproliferative disorders

Lymphoproliferative disorders refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in patients who have compromised immune systems...

, 22% of cases are follicular lymphomas.

External links

• An integrative medicine approach
• Resource page for follicular lymphoma
• Information on follicular lymphoma from Lymphoma Information Network