eMedicine Specialties > Hematology > Stem Cells and Disorders

Lymphoma, Follicular

Author: Cesar O Freytes, MD, FACP, Director of Bone Marrow Transplant Program, Professor, Department of Internal Medicine, Division of Hematology, University of Texas Health Science Center at San Antonio
Coauthor(s): Julianna A Burzynski, PharmD, BCOP, BCPS, Clinical Pharmacy Specialist in Hematology/Oncology, Mayo Clinic
Contributor Information and Disclosures

Updated: Nov 3, 2009

Introduction

Background

Non-Hodgkin lymphoma is a heterogeneous group of malignancies of lymphocyte origin that usually arise or are present in lymphoid tissues, such as lymph nodes, spleen, and bone marrow. Nevertheless, lymphomas can arise in any organ and usually are referred to as primary extranodal lymphomas. Microscopically, follicular lymphomas exhibit a follicular or nodular pattern of growth reminiscent of germinal centers. Despite the fact that most follicular lymphomas are advanced at the time of diagnosis, the median survival of patients with follicular lymphomas is approximately 8-10 years, and many patients may not require treatment for prolonged periods of time.1 (See images below and Images 1-3.)

Follicular lymphoma, low-power view: Note the nod...

Follicular lymphoma, low-power view: Note the nodular pattern reminiscent of germinal centers. Photograph courtesy of Aamir Ehsan, MD.

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Follicular lymphoma, low-power view: Note the nod...

Follicular lymphoma, low-power view: Note the nodular pattern reminiscent of germinal centers. Photograph courtesy of Aamir Ehsan, MD.


Diffuse lymphoma: Note the absence of the nodular...

Diffuse lymphoma: Note the absence of the nodular pattern observed in follicular lymphomas. Photograph courtesy of Aamir Ehsan, MD.

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Diffuse lymphoma: Note the absence of the nodular...

Diffuse lymphoma: Note the absence of the nodular pattern observed in follicular lymphomas. Photograph courtesy of Aamir Ehsan, MD.


A patient with follicular lymphoma who was diagno...

A patient with follicular lymphoma who was diagnosed 6 years earlier presents to his hematologist's office because of rapidly growing lymphadenopathy and a new onset of fever, severe night sweats, and weight loss. In the past, he had been treated with chlorambucil and prednisone when his submandibular lymph nodes became large enough to make him uncomfortable. This treatment had worked well, and he has not required any treatment recently. A biopsy of an involved lymph node is obtained (see image). The diagnosis is transformation to diffuse non-Hodgkin lymphoma.

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A patient with follicular lymphoma who was diagno...

A patient with follicular lymphoma who was diagnosed 6 years earlier presents to his hematologist's office because of rapidly growing lymphadenopathy and a new onset of fever, severe night sweats, and weight loss. In the past, he had been treated with chlorambucil and prednisone when his submandibular lymph nodes became large enough to make him uncomfortable. This treatment had worked well, and he has not required any treatment recently. A biopsy of an involved lymph node is obtained (see image). The diagnosis is transformation to diffuse non-Hodgkin lymphoma.


Pathophysiology

Most lymphomas originate from lymph node tissue and frequently metastasize to other organs. Lymphomas can invade any organ, including the skin and central nervous system. Lymphomas cause detrimental effects by organ invasion and by obstruction of anatomical structures by a tumoral mass.2,3 For example, ureteral obstruction by enlarged lymph nodes can lead to renal failure.

Frequency

United States

Non-Hodgkin lymphoma is the fifth most frequently diagnosed malignancy in the United States. Estimates indicate that more than 66,000 cases of non-Hodgkin lymphoma were diagnosed in 2008. Of those, 15-20% were follicular lymphomas.4

International

In general, age-adjusted incidence rates of non-Hodgkin lymphoma are higher in more developed countries. The age-adjusted incidence rates of non-Hodgkin lymphoma varied from 3.7-14 per 100,000 person years from 1983-1987 in different countries.

Mortality/Morbidity

  • The overall survival rate at 5 years is 72-77%. Median survival is approximately 8-10 years.
  • The Follicular Lymphoma International Prognostic Index (FLIPI) is predictive of survival in patients with follicular lymphomas. Five adverse prognostic factors have been shown to be correlated with reduced overall survival: age older than 60 years, Ann Arbor stage III or IV disease, hemoglobin less than 12 g/dL, presence of more than 4 nodal sites of disease, and serum lactate dehydrogenase above normal. Patients with 3 or more of the above risk factors have a 10-year overall survival rate of 36% compared with 71% for those with one or none of the above variables.

Race

Variations in racial incidence are found throughout the world. The incidence of follicular lymphomas is low in China and Japan. People of Jewish ancestry have a higher incidence of lymphoma. In the United States, the incidence is 2-3 times higher in Caucasians than in African Americans.

Sex

The male-to-female ratio is approximately 1:1.

Age

Median age at diagnosis is 60-65 years. The incidence of follicular lymphomas increases with age. Follicular lymphomas are extremely rare in children.

Clinical

History

  • Painless, slowly progressive adenopathy is the most frequent clinical presentation.
  • Some patients have waxing and waning adenopathy.
  • Systemic symptoms, such as fever, night sweats, weight loss in excess of 10%, or asthenia, are infrequent at presentation but can be observed in later stages of the disease. Progression to an intermediate-grade or high-grade lymphoma should be considered when a patient develops systemic symptoms.
  • Symptoms related to bone marrow dysfunction, such as anemia, leukopenia, or thrombocytopenia, are rare at presentation but can be observed in the later stages of the disease.

Physical

  • All lymph node areas should be examined, including the retroauricular, submandibular, cervical, supraclavicular, axillary, epitrochlear, inguinal, and popliteal areas.
  • Involved nodes typically are nontender, firm, and rubbery in consistency.
  • Splenomegaly is present in approximately 50% of patients at presentation.
  • The throat should be examined for involvement of the oropharyngeal lymphoid tissue (ie, Waldeyer ring).

Causes

  • Acquired nonrandom chromosomal translocations
    • The most common in patients with follicular lymphomas is the t(14;18) translocation, which is found in more than 80% of cases. This chromosomal translocation brings the bcl2 protooncogene under the transcriptional influence of the immunoglobulin heavy-chain gene. This translocation leads to the overexpression of a functionally normal bcl-2 protein. Overexpression of the bcl-2 protein, a protein of the mitochondrial membrane, confers a survival advantage to the cancer cells by inhibiting programmed cell death, or apoptosis. Although the exact mechanism of action of bcl-2 is unclear, its interaction with other homologs is felt to determine the likelihood of a cell undergoing apoptosis.
    • The detection of the t(14;18) product by polymerase chain reaction is used frequently in the diagnosis and follow-up of patients with follicular lymphomas. Nevertheless, this translocation has been detected in healthy patients and in patients with other types of tumors.
  • Viruses have been implicated as etiologic factors for lymphomas, including the Epstein-Barr virus, human T-cell lymphotropic virus type I, and the herpesvirus associated with Kaposi sarcoma (ie, human herpesvirus 8). Nevertheless, these viruses have been linked mostly to diffuse or high-grade lymphomas.
  • Chemicals, such as pesticides and hair dyes, have been associated with lymphoma.
  • Immunodeficiency states
    • Congenital immunodeficiencies have been associated with lymphoma.
    • Acquired immunodeficiencies may include infection with the human immunodeficiency virus. Most lymphomas associated with the human immunodeficiency virus are intermediate-grade or high-grade lymphomas.
    • Patients who have been on immunosuppressant drugs after organ transplantation may develop lymphoma. Most of the lymphomas observed after organ transplantation are diffuse or high-grade lymphomas.

More on Lymphoma, Follicular

Overview: Lymphoma, Follicular
Differential Diagnoses & Workup: Lymphoma, Follicular
Treatment & Medication: Lymphoma, Follicular
Follow-up: Lymphoma, Follicular
Multimedia: Lymphoma, Follicular
References
Further Reading
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References

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Keywords

follicular lymphoma, non-Hodgkin's lymphoma, nodular lymphomas, low-grade lymphomas, indolent lymphomas, non-Hodgkin lymphoma, lymphoid tissue, lymph nodes, spleen, bone marrow, primary extranodal lymphoma

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Contributor Information and Disclosures

Author

Cesar O Freytes, MD, FACP, Director of Bone Marrow Transplant Program, Professor, Department of Internal Medicine, Division of Hematology, University of Texas Health Science Center at San Antonio
Cesar O Freytes, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Association for the Advancement of Science, American Association of Blood Banks, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, International Society for Experimental Hematology, and New York Academy of Sciences
Disclosure: Genzyme Grant/research funds Review panel membership; Otsuka Consulting fee Review panel membership

Coauthor(s)

Julianna A Burzynski, PharmD, BCOP, BCPS, Clinical Pharmacy Specialist in Hematology/Oncology, Mayo Clinic
Julianna A Burzynski, PharmD, BCOP, BCPS is a member of the following medical societies: American College of Clinical Pharmacy
Disclosure: Nothing to disclose.

Medical Editor

Koyamangalath Krishnan, MD, FRCP, FACP, Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University
Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center
Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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