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Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, encompasses a diverse group of blood cancers that exclude Hodgkin lymphomas. These cancers originate from lymphocytes, a type of white blood cell, and can vary significantly in their clinical presentations and progression rates.

Micrograph of mantle cell lymphoma, a type of non-Hodgkin lymphoma. Terminal ileum. H&E stain.
Micrograph of mantle cell lymphoma, a type of non-Hodgkin lymphoma. Terminal ileum. H&E stain.

Signs and Symptoms

The manifestations of NHL depend on its anatomical location within the body. Common symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and fatigue. Additional symptoms may include bone pain, chest pain, or itchiness. Some forms of NHL grow slowly, while others are more aggressive. Enlarged lymph nodes may be palpable under the skin if they are superficial. Lymphomas in the skin can present as itchy, red, or purple lumps. When lymphomas affect the brain, they can cause neurological symptoms such as weakness, seizures, cognitive impairments, and personality changes.


Diagnosing NHL involves several tests:

  • Complete blood count (CBC)
  • Blood chemistry studies
  • Hepatitis B and C tests
  • HIV test
  • Imaging studies like CT scans and PET scans
  • Bone marrow aspiration and biopsy

If cancer is detected, further analyses such as immunohistochemistry, cytogenetic analysis, and immunophenotyping help determine the specific characteristics of the cancer cells. Additional tests may be required based on the specific symptoms and cancer location.

Causes and Risk Factors

The aetiology of NHL is multifactorial, with various potential causes and associations:

  • Infectious agents: Epstein–Barr virus (associated with Burkitt's lymphoma and others), Human T-cell leukaemia virus, Helicobacter pylori (linked with gastric lymphoma), and Hepatitis C virus.
  • Chemical exposures: Polychlorinated biphenyls (PCBs), dioxin, and certain herbicides.
  • Medical treatments: Prior radiation therapy and chemotherapy.
  • Genetic factors: Conditions like Klinefelter syndrome and ataxia–telangiectasia.
  • Autoimmune diseases: Conditions such as Sjögren syndrome and systemic lupus erythematosus.
  • Other factors: Bone trauma, implants, and a familial predisposition to lymphoid cancers.


Treatment strategies for NHL depend on the type and stage of the lymphoma, as well as the patient's overall health. Options include:

  • Chemotherapy: The R-CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) is commonly used for B-cell NHL. R-CHP with polatuzumab vedotin is another preferred regimen for certain cases.
  • Radiation therapy: Often used in combination with chemotherapy.
  • Immunotherapy: Uses the body's immune system to fight cancer cells.
  • Targeted therapy: Drugs specifically designed to target cancer cell mechanisms.
  • Stem cell transplantation: Used in some aggressive forms of NHL.
  • Surgery: Rarely used, except for specific localised cases.
  • Watchful waiting: Monitoring slow-growing lymphomas without immediate treatment.

Treatment Complications

Complications from treatment can include graft-versus-host disease in stem-cell transplantation and increased risk of bleeding, necessitating platelet transfusions. Additionally, aerobic physical exercise may help manage fatigue and depression but has limited impact on overall mortality and quality of life.


The prognosis of NHL varies widely based on subtype, stage, patient age, and other factors. Generally, the five-year survival rate for NHL in the United States is around 71-74%.


NHL incidence increases with age and is more common in males up to 45 years. In 2015, 4.3 million people were affected globally, with 231,400 deaths. In the UK, approximately 13,900 cases are diagnosed annually, making it the sixth most common cancer. In the US, 2.2% of people will be diagnosed with NHL in their lifetime, with an age-adjusted rate of 19.6 cases per 100,000 adults per year.


The classification of NHL has evolved over time, with the Working Formulation introduced in 1982 standardising the term "non-Hodgkin lymphoma" and categorising lymphomas by their aggressiveness. Despite the diverse nature of NHL, this classification remains widely used for disease statistics and clinical management.

Self-assessment MCQs (single best answer)

Which of the following is NOT a common symptom of Non-Hodgkin Lymphoma (NHL)?

What type of white blood cell does Non-Hodgkin Lymphoma originate from?

Which virus is associated with Burkitt's lymphoma?

Which of the following is NOT a diagnostic test for NHL?

The R-CHOP regimen includes all of the following drugs EXCEPT:

Which of the following is a potential complication of stem cell transplantation in NHL treatment?

Which infectious agent is linked with gastric lymphoma?

Which of the following treatments is RARELY used for NHL?

What is the approximate five-year survival rate for NHL in the United States?

What classification system introduced in 1982 helped standardise the term "non-Hodgkin lymphoma"?


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