Non-Hodgkin's lymphoma is a heterogeneous group of lymphoproliferative malignancies.
It is the most common hematologic cancer.
The most common subtypes are the diffuse large B-cell and follicular lymphoma. The subtypes are based on the malignant cell's morphology, genetic features, immunohistological characteristics, and stage of maturation.


  • The most common hematologic cancer
  • B-cell non-Hodgkin's lymphoma (NHL) are 80-85% more common than T-cell/NK cell NHLs (15-20%)
  • Advances in molecular genetics allowed better understanding of the pathophysiology & further identification of the different subtypes of NHL
  • NHL subtypes are based on the malignant cell's morphology; genetic features, immunohistological characteristics & stage of maturation


  • A heterogenous group of lymphoproliferative malignancies formed by either B-cells or T-cell/natural killer (NK) cells


Causes of Non-Hodgkin's Lymphoma (NHL)
  • Genetic aberrations & lesions
    • p53 tumor suppressor gene deletions/alterations (eg Burkitt lymphoma, follicular lymphoma, mantle cell lymphoma)
    • Chromosomal deletions (eg chromosome 6q, chromosome 13q14)
    • Chromosomal translocations (eg follicular lymphoma - t[14;18][q32;q21], MCL - t[11;14][q13;q32])
  • Oncogenic viruses (eg Epstein-Barr virus, Human T cell lymphotropic virus I, Human Herpes virus-8)

Signs and Symptoms

Clinical Evaluation
  • Assess patient’s performance status based on the clinical presentation
  • Systemic B-cell symptoms
    • Present in aggressive types of NHLs
    • Fever
    • Night sweats
    • Weight loss
  • Indolent types of NHL
    • Splenomegaly
    • Hepatomegaly
    • Lymphadenopathy
    • Cytopenia
  • Nonspecific signs & symptoms
    • Skin rash
    • Generalized fatigue
    • Fever of unknown origin
    • Pleural effusion
    • Pruritus
    • Malaise
    • Ascites
  • Lymphoma with gastrointestinal tract involvement
    • Anorexia
    • Weight loss
    • Bloatedness
    • Pallor
    • Nausea/vomiting
    • Abdominal pain
    • Early satiety
    • Intestinal bleeding
  • Lymphoma with central nervous system involvement
    • Headache
    • Blurred vision
    • Paralysis
    • Dizziness
    • Seizures
    • Focal neurologic symptoms
  • Adult T-cell leukemia/lymphoma
    • Lymphadenopathy
    • Fatigue
    • Anorexia
    • Splenomegaly
    • CNS involvement
    • Pulmonary complications
    • Skin eruptions
    • Abdominal pain
    • Hepatomegaly
    • Bone marrow involvement
  • Burkitt lymphoma
    • Bone marrow (70%) involvement
    • Leptomeningeal CNS involvement (40%)
  • Extranodal NK/T-cell lymphomas, nasal type
    • Nasal obstruction
    • Nasal bleeding secondary to mass lesion
    • Elevated LDH levels

Risk Factors

  • Acquired immunosuppression (previous organ/bone marrow/stem cell transplant, HIV, AIDS)
  • Congenital immunodeficiency syndromes
  • Old age
  • Positive family history of NHL
  • Positive medical history of Hodgkin lymphoma
  • Chemical exposures (pesticides, wood dust, epoxy glue, organic solvents, medication [eg Methotrexate, TNF-α inhibitors])
  • Radiation exposure
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