creation date: 2025-09-15 16:26
tags: Pathologies, Incomplete
Non-Hodgkin Lymphoma
Background
Definitions
Non-Hodgkin lymphoma (NHL) is a neoplasm of the lymphoid tissues. NHL comprises of various subtypes. Subdivision can be by:
- Cell lineage (B-cell, T-cell, or NK-cell origin)
- Clinical behaviour (indolent or aggressive)
- Specific characteristics (eg. morphology, immunophenotype, genetic features, and molecular profiles)
Widely accepted are the WHO or ICC classifications which recognize >80 distinct variants.
Major subdivisions are:
B-cell lymphomas
- Diffuse large B-cell lymphomas*
- Follicular lymphoma*
- Mantle cell lymphoma
- Burkitt lymphoma*
- Marginal zone lymphoma
- Lymphoplasmacytic lymphoma
T-cell and NK-cell lymphomas - Peripheral T-cell lymphoma
- Angioimmunoblastic T-cell lymphoma
- Anaplastic large cell lymphoma
- Extranodal NK/T-cell lymphoma
Precursor lymphoid neoplasms - Lymphoblastic lymphoma/leukemia of B- or T-cell origin
*Most common types
Etiology
The origin of NHL vary between subtype but is generally associated with factors such as infections, environmental factors, immunodeficient state, and chronic inflammation.
Some infectious agents are:
- EPV - Burkitt lymphoma
- Human T-cell leukemia virus type 1 - adult T-cell lymphoma
- Hepatitis C virus - clonal V-cell expansions (eg. diffuse large B-cell lymphoma)
- Human herpesvirus 8 - primary effusion lymphoma
- Helicobacter pylori - gastric mucosa-associated lymphoid tissue lymphomas
Drugs that are associated with NHL are:
- Phenytoin
- Digoxin
- TNF antagonist
- Other carcinogenic agents (eg. pesticides, solvents)
Congenital immunodeficiency states and autoimmune disorders are also associated with increased risk of NHL.
Pathogenesis
Non-Hodgkin lymphomas arise from lymphocytes due to chromosomal translocation and/or mutation/deletion, in which proto-oncogenes are activated and tumour suppressor genes are inactivated, respectively.
Depending on the genes affected, various forms of lymphoma arise.
Clinical Presentation
Signs & Symptoms
The exact presentation of patient depends on the type of lymphoma.
Indolent lymphomas
- Waxing/waning lymphadenopathy
- Time over many years
Aggressive lymphomas - Specific B symptoms (ie. weight loss, night sweats, fever)
- Can progress rapidly to death within weeks
General findings include:
- Peripheral lymphadenopathy
- Skin rashes
- Increased hypersensitivity reactions to insect bites
- Generalized fatigue
- Pruritus
- Malaise
- Fever of unknown origin
- Ascites
- Effusions
Extranodal disease may present with symptoms specific to region of disease.
History & Physical Exam
Risk factors
Diagnosis
Criteria
Work-up
Workup should include:
- CBC with differential
- Serum chemistries (to r/o tumour lysis syndrome) including LDH (for tumour burden)
- Imaging (CT neck, chest, abdo, pelvis) or PET scan; MRI of brain/spinal cord may be needed
- Lymph node biopsy if abnormal, with immunophenotypic analysis
- Lumbar puncture if high risk of CNS involvement
Bone marrow aspiration and biospy may be needed to stage NHL but PET scans may be sufficient.
Differential
- Hodgkin lymphoma
- Epstein Barr virus infection
- Systemic lupus erythematosus
- Intussusception
- Appendicitis
- Toxoplasmosis
- Metastasis from the primary tumor (eg, nasopharyngeal carcinoma, soft tissue sarcoma)
- Malignancies or lymphoproliferative disorders like granulocytic sarcoma and multicentric Castleman disease.
- Mycobacterial and other bacterial infections cause benign lymph node infiltration and reactive follicular hyperplasia.
Red Flags / Complications
Management
The treatment of NHL is based on type, stage, histopathological features, and symptoms. These include chemotherapy, radiotherapy, immunotherapy, stem cell transplants, and rarely, surgery.
References
Tools / Guidelines
Additional Reading
World Health Organization (WHO) Classification of Haematolymphoid Tumours