Follicular lymphomas (or more formally speaking, follicular center cell lymphomas with a follicular growth pattern) are one of the more common non-Hodgkin's lymphomas in North America. They afflict almost exclusively adults, particularly the middle-aged and elderly. They are of B-cell lymphocyte origin. Because the small-cleaved cells of follicular lymphomas know how to circulate in the blood, patients usually present with disseminated lymphadenopathy (lymphoma in multiple parts of the body). Nonetheless these lymphomas have a better prognosis than higher grade lymphomas.

Causes

Most cases of follicular lymphoma, especially those rich in small-cleaved cells, have a t(14;18) gene translocation. This results in a rearranged and constitutively over-expressed gene called BCL-2.

The BCL-2 gene tells the body to produce an inner mitochondrial membrane protein that blocks programmed cell death (apoptosis). Although this protein is produced by an unrearranged BCL-2 gene in much benign (non-cancerous) lymphoid tissue and is present in many lymphomas besides follicular ones, it is not detected in benign, reactive germinal center cells

Follicular Cell Lymphomas: A Breakdown

Follicular lymphomas are divided into 3 types according to the ratio of small-cleaved and large cells:

1. Small-cleaved cell type has less than 20-25% large cells, or fewer than 5 large cells per high power field. This lymphoma is rich in small-cleaved cells, which know how to voyage in the blood and are often found there as well as in the marrow and liver. Patients nevertheless have a median survival of 7.5-9 years. As in other indolent lymphomas, however, standard chemotherapy cannot secure a protracted remission or cure.

2. Mixed small-cleaved and large cell type has between 20-25% and 50% large cells or between 5 and 15 large cells per high power field. Though these lymphomas are also indolent (low grade in the Working Formulation), the increased percentage of large cells is associated with a reduced average survival.

3. Large cell type has more than 50% large cells, or more than 15 large cells per high power field. Large cell lymphomas with a follicular growth pattern are uncommon, and the nodularity can be hard to perceive. These lymphomas are the only intermediate grade follicular lymphomas - they are classified as indolent but their aggressive nature is noted by NCI.

Treatment

Treatment options depend on the stage and grade of the disease. The infrequent adult patients with early-stage disease may be treated with local radiation, with or without hemotherapy . Patients with more advanced but low-grade disease may remain untreated as long as no symptoms or lymphoma-related organ compromise are present (watch and wait). When treatment becomes necessary, the options include:

1) single-agent alkylator chemotherapy
2) low-intensity combined chemotherapy without an anthracycline
3) whole-body irradiation

Large-cell follicular lymphoma is classified as an intermediate-grade lymphoma, and the patients may benefit from the inclusion of an anthracycline in their chemotherapy. Immunotherapy and Monoclonal Antibody Therapy specifically has shown promise in the treatment of follicular lymphomas recently. This includes drugs such as Rituxan (rituximab / MabThera) and possibly others like Bexxar and Zevalin.

T-cell immunotherapy

Cytotoxic T-lymphocytes (CTL), also known as “killer” T-cells, are also an important component of the immune system and specifically directing these immune cells to fight lymphoma cells by gene therapy is an emerging technology. Genetically modified CTL can recognize lymphoma cells like a monoclonal antibody, but then attack the lymphoma cells like a “killer” T-cell. At the Fred Hutchinson Cancer Research Center in Seattle, lymphoma researchers have started using this gene therapy approach following chemotherapy to treat patients with relapsed follicular non-Hodgkin’s lymphoma. For more information about this study, call +1-206-667-5184 or go to http://www.fhcrc.org/cancer_info/studies/1503.html

 

 

Resources

Web Sites

CancerBackup - Follicular Lymphoma (UK) (new name)
The Hematopathology site has a great, often times technical, discussion of follicular lymphoma.

Survivor Sites

Robert Miller is a survivor of follicular and diffuse lymphoma with articles on his site.

Mailing Lists

See the mailing list page for NHL (many) and Follicular (1) mailing lists

Reference Sources

NCI Non-Hodgkin's Lymphoma Information
The Hematopathology discussion of follicular lymphoma
A paper in the Cancer Control Journal: Indolent Lymphomas: Classic Subtypes and Newer Entities
Frontiers in Bioscience is a source of B-cell information.
ESMO Clinical Recommendations for newly diagnosed follicular lymphoma

 

Related Articles

Non-Hodgkin's Lymphoma Information Pages:

Non-Hodgkin's Lymphomas
Non-Hodgkin's Lymphoma: Diagnosis
Non-Hodgkin's Lymphoma: Aggressive Lymphomas
Non-Hodgkin's Lymphoma: Indolent Lymphomas
Non-Hodgkin's Lymphoma: Treatment
Non-Hodgkin's Lymphoma: Resources
Bone Marrow and Stem Cell Transplants

Childhood Lymphoma Information Pages:

Childhood Lymphoma
Childhood Non-Hodgkin's Lymphoma

 

Books

Non-Hodgkin's Lymphomas, Peter M. Mauch (Editor), James O. Armitage (Editor), et al., 2004.

Section IV: Pathology, Biology, Clinical Evaluation, and Treatment Section

Chapter 24: Follicular Lymphoma

Living With Lymphoma, Elizabeth Adler, Oct. 2005

Chapter 10: Lymphoma Classification and Staging Follicular Lymphomas, pp. 298-301