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Non-Hodgkin Lymphoma (NHL)

Non-Hodgkin Lymphoma (NHL) is a heterogeneous group of lymphoid malignancies arising from B lymphocytes, T lymphocytes, or natural killer (NK) cells. Unlike Hodgkin lymphoma, NHL lacks Reed-Sternberg cells and often spreads in a non-contiguous pattern

Also called

Non-Hodgkin's Lymphoma (older term)

ICD-10

C85

Specialty

Hematology

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

Non-Hodgkin Lymphoma (NHL) is a diverse group of lymphoid cancers that vary from indolent (slow-growing) to highly aggressive forms. Most cases arise from B cells, with Diffuse Large B-cell Lymphoma (DLBCL) being the most common aggressive subtype and Follicular Lymphoma the most common indolent subtype. Diagnosis is established by excisional lymph node biopsy, and treatment depends on the histological subtype and stage.

Etiology & Risk Factors

-Etiology

The exact cause is unknown. Non-Hodgkin Lymphoma (NHL) develops through acquired genetic mutations causing malignant transformation of lymphocytes.

Risk Factors

  • Increasing age

  • Immunodeficiency (HIV/AIDS)

  • Organ transplantation

  • Autoimmune diseases

  • Epstein-Barr virus (EBV)

  • Helicobacter pylori (gastric MALT lymphoma)

  • Hepatitis C virus

  • Human T-cell leukemia virus-1 (HTLV-1)

  • Previous chemotherapy or radiotherapy

  • Family history

  • Exposure to pesticides or certain chemicals

Pathophysiology

Genetic mutations in B, T, or NK lymphocytes → uncontrolled clonal proliferation → accumulation of malignant lymphocytes in lymph nodes, bone marrow, spleen, and extranodal organs → replacement of normal tissue → impaired immune function and bone marrow failure in advanced disease. Unlike Hodgkin lymphoma, NHL often spreads non-contiguously and frequently involves extranodal organs such as the gastrointestinal tract, skin, bone marrow, or central nervous system

Clinical Presentation

Symptoms

  • Painless lymph node enlargement

  • Fatigue

  • Fever

  • Night sweats

  • Weight loss

  • Abdominal pain

  • Early satiety

  • Persistent cough

  • Dyspnea

  • Recurrent infections

Signs

  • Generalized lymphadenopathy

  • Splenomegaly

  • Hepatomegaly

  • Pallor

  • Petechiae

  • Extranodal masses

B Symptoms

  • Fever (>38°C)

  • Drenching night sweats

  • Unintentional weight loss (>10% over 6 months)

History Taking

-Ask about:

  • Duration of lymph node enlargement
  • Fever
  • Night sweats
  • Weight loss
  • Fatigue
  • Recurrent infections
  • Abdominal pain
  • Gastrointestinal symptoms
  • Skin lesions
  • HIV status
  • Autoimmune disease
  • Previous chemotherapy or radiation
  • Family history

Physical Examination

-General Examination

Look for:

  • Fever

  • Pallor

  • Weight loss

-Lymph Node Examination

Assess for:

  • Cervical lymphadenopathy

  • Axillary lymphadenopathy

  • Inguinal lymphadenopathy

-Abdominal Examination

Assess for:

  • Splenomegaly

  • Hepatomegaly

  • Abdominal masses

-Additional Examination

Look for:

  • Skin lesions

  • Neurological deficits (if CNS involvement)

  • Signs of extranodal disease

Investigations

-Complete Blood Count (CBC)

May show:

  • Anemia

  • Leukopenia or leukocytosis

  • Thrombocytopenia (bone marrow involvement)

Blood Tests

  • LDH (prognostic marker)

  • Uric acid

  • Liver function tests

  • Renal function tests

  • HIV test

  • Hepatitis B and C screening

  • Beta-2 microglobulin

-Excisional Lymph Node Biopsy (Gold Standard)

Required for:

  • Histological diagnosis

  • Immunophenotyping

  • Subtype classification

Immunophenotyping

Common B-cell markers:

  • CD19

  • CD20

  • CD22

  • CD79a

Additional markers according to subtype.

-Bone Marrow Aspiration and Biopsy

Performed for staging and assessment of marrow involvement.

-Imaging

  • PET-CT scan (preferred for staging in FDG-avid lymphomas)

  • CT neck, chest, abdomen, and pelvis

-Cytogenetic & Molecular Studies

Performed according to subtype:

  • MYC rearrangement

  • BCL2 rearrangement

  • BCL6 rearrangement

  • FISH and molecular testing when indicated

Diagnosis

Diagnosis is based on:

  • Excisional lymph node biopsy
  • Immunophenotyping
  • Histological classification
  • Bone marrow examination (when indicated)
  • PET-CT staging
  • Ann Arbor staging system
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Related Topics

Management

–Indolent Non-Hodgkin Lymphoma (NHL)

  • Active surveillance (selected asymptomatic patients)

  • Rituximab-based therapy

  • Radiotherapy for localized disease

-Aggressive NHL

  • R-CHOP chemotherapy

    • Rituximab

    • Cyclophosphamide

    • Doxorubicin

    • Vincristine

    • Prednisolone

-Relapsed or Refractory Disease

  • Salvage chemotherapy

  • Autologous hematopoietic stem cell transplantation

  • CAR T-cell therapy (selected patients)

  • Targeted therapies according to subtype

-Supportive Care

  • Infection prevention

  • Tumor lysis syndrome prophylaxis

  • Blood transfusions if required

  • Vaccination when appropriate

Complications

  • Bone marrow failure
  • Severe infections
  • Tumor lysis syndrome
  • Superior vena cava syndrome
  • CNS involvement
  • Relapse
  • Secondary malignancies
  • Treatment-related toxicity

Prognosis

The prognosis depends on the lymphoma subtype, stage, patient age, performance status, and response to therapy. Indolent lymphomas usually have prolonged survival but frequent relapses, whereas aggressive lymphomas may be curable with appropriate treatment. The International Prognostic Index (IPI) is commonly used to estimate prognosis in aggressive Non-Hodgkin Lymphoma (NHL).

Key Points / Clinical Pearls

  • Non-Hodgkin Lymphoma (NHL) is a heterogeneous group of lymphoid malignancies.
  • Most cases arise from B lymphocytes.
  • Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive subtype.
  • Follicular lymphoma is the most common indolent subtype.
  • NHL does not contain Reed-Sternberg cells.
  • Extranodal involvement is common.
  • Excisional lymph node biopsy is the gold standard for diagnosis.
  • PET-CT is preferred for staging aggressive NHL.
  • R-CHOP is the standard first-line treatment for most DLBCL patients.
  • Prognosis varies according to the lymphoma subtype, stage, and response to treatment