What Is Follicular Lymphoma?

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Follicular Lymphoma is a type of blood cancer arising from a group of white blood cells ( also known as immune cells) called B lymphocytes. This cancer occurs commonly in lymph nodes but can also occur in other organs such as the bone marrow and liver. While most of the time, it is a slow-growing cancer, it can progress into more aggressive behaviour. 

Overview

Cancers arising from lymphocytes are broadly called lymphomas, and there are two main categories: Hodgkin and non-Hodgkin lymphomas.1 Follicular lymphoma belongs to the latter category.

Follicular lymphoma may present as a painless enlargement of lymph nodes and/or with systemic symptoms like a low-grade fever or unexplained weight loss.2 The patient may also present with bone marrow disease that will cause symptoms of reduced red blood cell production like anaemia or reduced platelet counts. Follicular lymphoma is common in those around 60 or above years of age, although there is also a subtype that occurs in children.12

The diagnosis of Follicular lymphoma needs a biopsy, meaning a sample of tissue taken from the patient's enlarged lymph node for testing under the microscope. The treatment varies from radiotherapy in the early stages of the disease to more systemic therapy like chemotherapy for more advanced stages. 

Most of the time, follicular lymphoma cannot be cured and can keep recurring.3

Introduction to follicular lymphoma

Follicular lymphoma is the second most common type of non-Hodgkin lymphoma. This is a type of cancer of a type of white blood cells called B cells. The tumour is caused by a swap between some genetic material units that control the growth of these cells.6 The genetic swap leads to uncontrolled growth of B-lymphocytes. This swap can often be detected by advanced genetic tests.

Who can be affected by follicular lymphoma?

Follicular lymphoma commonly affects older adults, though there is a form of children’s cancer of the same type.5 According to data from The Cleveland Clinic, the cancer is seen in 3 to 4 people per 100,000. The Cleveland Clinic also reports the incidence of follicular lymphoma to be slightly higher in people assigned to males than those assigned to females. 

Causes and risk factors

The cause of Follicular lymphoma is not yet fully understood. However, it is reported that exposure to some environmental chemicals, certain viral infections or immune suppression by various illnesses or medications can cause most non-Hodgkin lymphomas.2

Signs and symptoms

The main symptoms of follicular lymphoma occur in the lymph nodes. This is usually swelling of those glands in your neck region, armpits or in your groin.1 These swellings are generally painless.

The other symptoms, known as ‘B symptoms’, include ‘drenching’ night sweats, low-grade fever and weight loss.1 Unexplained itching of your body can also occur,1 although there may be due to other causes.

Diagnosis

  • Lymph node biopsy:  To diagnose Follicular lymphoma, a sample from the enlarged lymph node is needed and this is called a biopsy. This will then be processed in the laboratory and checked under a microscope. An immunohistochemistry was performed on the biopsy to confirm the diagnosis. These are special tests that highlight the tumour cells to differentiate them from others. 
  • Bone marrow biopsy: Sometimes, the same testing may be done on tissue taken from bone marrow. This is a slightly more complicated procedure of retrieving tissue.
  • Blood tests: Blood tests may be needed to assess the patient further 
  • Imaging: Some imaging like CT scans or even PET scans may be needed to detect the spread of the disease in other potentially affected nodes or organs

Grading and staging

The grading of Follicular lymphoma is based on its microscopic appearance, which can show varying cell types.2 This grading system contains three categories from 1 to 3, with 3 subdivided into 3a and 3b. Grade 3 tumours behave like a typical aggressive high-grade lymphoma.

The staging system categorises how far Follicular Lymphoma has spread in the body. There is a special staging method called ‘Cotswold Modified Ann Arbour Staging’12 to assess the spread of the lymphoma.

According to Cleveland Clinic, this staging depends on how many of your lymph nodes are affected, whether they are above or below the diaphragm level, on both sides of the body, and also whether bone marrow or other organs are affected. 

Additional factors such as B-symptoms, tumour bulk and tumour presence outside of lymph nodes are also considered in this staging system.

According to the staging system, stage 1 and some of stage 2 are considered limited diseases, while stages 3 and 4 are considered to be advanced diseases.1

Treatment options

Treatment for Follicular lymphoma is largely based on the stage of the disease. Radiotherapy is used as a treatment for most stage 1 and some stage 2 cases since these stages are considered limited diseases.5 In selected cases, no prolonged treatment may be used right away if the diseased lymph node can be surgically removed. In this case,  there will be regular checkups to see if the tumour recurs.1

For certain stage 2 tumours, a drug therapy using mono clonal antibodies is used with or without chemotherapy. This therapy option is also used for stages 3 and 4.

In addition, there are treatment methods called  Immunotherapy, which involves utilising the body’s own immunity mechanisms.6

There is an immunotherapy regime called R squared in which two drugs called Rituximab and Revlimid are used, which some patients may be eligible for.

Immunotherapy sometimes takes longer than chemotherapy, but it can help you avoid its side effects like nausea, fatigue and hair loss 6

Haematopoetic stem cell transplant is also another advanced treatment option available for follicular lymphoma that is offered to patients who get recurrences, especially younger patients.3

Prognosis and outlook

The outcome for Follicular Lymphoma is based on a few factors: age of the patient, stage of the disease, number of lymph nodes involved, and  LDH and Hemoglobin levels in the blood. This is called the FLIPI index, and it categorizes patients into low, intermediate and high-risk groups with different overall survival rates.10,11

Supportive care and lifestyle

Supportive care and lifestyle play crucial roles in managing follicular lymphoma. While medical treatments target the cancer directly, supportive care focuses on improving patients' overall well-being and quality of life. This includes addressing symptoms like fatigue, pain, and side effects of treatment. Maintaining a healthy lifestyle by staying active, eating a balanced diet, and managing stress can further contribute to the patient's comfort and resilience. 

Ongoing research and advancements

Ongoing research and advancements in the field of follicular lymphoma are bringing hope for improved treatments and outcomes. Scientists and doctors are working to better understand the disease's underlying mechanisms, which can lead to more targeted and effective therapies. 

New drugs and treatment approaches are being developed, aiming to minimize side effects and enhance patients' quality of life. Clinical trials are a crucial part of this progress, allowing patients to access cutting-edge treatments before they become widely available. As researchers continue to unravel the complexities of follicular lymphoma, there is optimism that these efforts will lead to even more personalized and successful strategies for managing the disease in the future.

Summary

Follicular lymphoma is a cancer of B-lymphocytes, which are a type of immune cell (white blood cells) in the body. It belongs to a group of blood cancers called non-Hodgkin lymphomas. While it is usually a slow-growing tumour, it acts aggressively in its advanced stages. Follicular lymphoma is commonly a disease of the elderly, but it can happen in children, called the paediatric type.

The cancer commonly presents as enlarged, painless lymph nodes or glands in your body, especially in the neck, armpits or groin. Some general symptoms like unexplained fever, weight loss or night sweats can occur. A doctor will examine you and often will need to take a sample of your enlarged nodes for testing. They may also do blood tests and imaging tests to see how much it has spread. Rarely, tests on bone marrow may need to be done.

Follicular lymphoma is graded with a number and also staged according to how much it has spread. If Follicular lymphoma is in its early stages, the treatment may be limited therapy like radiotherapy or, for later stages,  chemotherapy will need to be added on. The outcome and survival depend on the stage at diagnosis, age and other factors.

There are no known risk factors specific to Follicular lymphoma. In general, for all non-Hodgkin’s lymphomas, chemicals, viruses and immunosuppression are postulated as causes. Follicular lymphoma tends to reoccur, and long-term monitoring is needed.

Reference

  1. Follicular lymphoma | non-Hodgkin lymphoma | Cancer Research UK [Internet]. www.cancerresearchuk.org. Available from: https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/types/follicular-lymphoma
  2. Follicular Lymphoma: Practice Essentials, Etiology and Pathophysiology, Epidemiology. eMedicine [Internet]. 2021 Jul 15; Available from: https://emedicine.medscape.com/article/203268-overview
  3. Follicular Lymphoma [Internet]. Lymphoma Research Foundation. [cited 2023 Aug 10]. Available from: https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/follicular-lymphoma/
  4. Follicular-usual [Internet]. www.pathologyoutlines.com. Available from: https://www.pathologyoutlines.com/topic/lymphomafollicularnodalusual.html
  5. Mayo Clinic. Non-Hodgkin’s lymphoma - Symptoms and causes [Internet]. Mayo Clinic. 2018. Available from: https://www.mayoclinic.org/diseases-conditions/non-hodgkins-lymphoma/symptoms-causes/syc-20375680
  6. Adams M. 7 questions about follicular lymphoma, answered [Internet]. MD Anderson Cancer Center. [cited 2023 Aug 10]. Available from: https://www.mdanderson.org/cancerwise/7-questions-about-follicular-lymphoma--answered.h00-159541323.html
  7. Blood Cancer UK | Follicular lymphoma prognosis [Internet]. Blood Cancer UK. 2023 [cited 2023 Aug 10]. Available from: https://bloodcancer.org.uk/understanding-blood-cancer/lymphoma/follicular-lymphoma/follicular-lymphoma-prognosis/?gad=1&gclid=Cj0KCQjwz8emBhDrARIsANNJjS5yUxcjoOFlvnHiAeAjcsZDEgy5Wj3gm2c1v9VynAIA0Ura5FSmsu0aAnZhEALw_wcB
  8. Carbone A, Roulland S, Gloghini A, Younes A, von Keudell G, López-Guillermo A, et al. Follicular lymphoma. Nature Reviews Disease Primers. 2019 Dec;5(1).
  9. Jacobsen E. Follicular lymphoma: 2023 update on diagnosis and management. American Journal of Hematology. 2022 Sep 17;97(12).
  10. Follicular-usual [Internet]. www.pathologyoutlines.com. Available from: https://www.pathologyoutlines.com/topic/lymphomafollicularnodalusual.html
  11. Follicular Lymphoma (Non-Hodgkin Lymphoma) Staging: Classification and Staging Systems for Follicular Lymphoma. eMedicine [Internet]. 2020 Mar 22; Available from: https://emedicine.medscape.com/article/2007038-overview
  12. Pediatric type [Internet]. www.pathologyoutlines.com. [cited 2023 Aug 10]. Available from: https://www.pathologyoutlines.com/topic/lymphomafollicularchildhood.html

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Varuni Upamali Fernando

MBBS(Colombo), DipRCpath, CHCCT(UK)

Curent role as Specialty Doctor in Histopathology and previously as Associate Specialist in GI pathology. STEM ambassador and former freelance copywriter for advertising agencies and healthcare institutes.

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