Non-Hodgkins Lymphoma

» Haematology» Oncology

Overview

Lymphomas are derived from B and T lymphocytes or natural killer (NK) cells at varying stages of maturation. B cell lymphomas can arise at any stage of normal B cell development, but most are derived from cells that have been exposed to the germinal center reaction. T and natural killer (NK) cell lymphomas can arise at any stage of normal T or NK cell development. B cell lymphoma are more common.

Epidemiology

Lymphoma is divided into Hodgkins and Non-Hodgkins Lymphoma (NHL)
NHL accounts for 90% of all lymphomas
The incidence of NHL increases with age.
They are uncommon before age 50 years.
The relative incidences of some of the most important types of NHL are:
- Diffuse large B-cell lymphoma (DLBCL)
- Follicular lymphoma (FL)
- The rest have 1% or lower incidence

Sign and Symptoms

Night sweats
Weight loss
Fatigue
Fever
Lympadenopathy
Splenomegaly
Shortness of breath
Cough
Anaemia

Differential Diagnosis

Hodgkins Lymphoma (bimodal age distribution at diagnosis -peaks at mid-20s and mid-60s, lymph node biopsy reveals Reed-Sternberg Cells)
Acute Lymphoblastic Leukemia (acute onset, purpura, bleeding, and infection are key presenting symptoms.)
Infectious mononucleosis (self-limiting condition with abrupt onset of symptoms; pharyngitis, rash and myalgias) - also known as the kissing disease
Tuberculosis
Rheumatoid Arthritis
Systemic lupus erythematosus (SLE) (characteristic butterfly rash, photosensitivity, oral ulcers, arthritis)

Acute lymphoblastic leukaemia tetrad: acute onset, purpura, bleeding, and infection

Risk Factors

Immunological

Autoimmune Diseases
Immunodeficiency

Genetic

Klienfelters Syndrome
SCID

Viral

Hepatitis C Virus (HCV)
HIV
EBV

Environmental

Herbicides
Pesticides
Smoking

Investigations and Diagnosis

Full blood count (thrombocytopenia, pancytopenia)
Blood smear (nucleated red blood cells, giant platelets)
Lymph node biopsy
Bone marrow biopsy
- 30-50% of patients have involvement of bone
LDH (elevated and is a indirect indication of proliferative rate of lymphoma)
Erythrocyte sedimentation rate (elevated)
CT scan (staging tool)
Immunophenotype studies (Sub-classification of most forms of NHL)
Flow cytometry -> on a single cell
Immunohistochemistry -> on a tissue

Diagnosis

Lymph, Skin or Bone Marrow Biopsy can be used for diagnosis depending on the type of NHL. Imaging for monitoring progression (CT, PET)

Ann Arbor Staging System for NHL

I: Single lymph node group
II: Multiple lymph node groups on same side of diaphragm
III: Multiple lymph node groups on both sides of diaphragm
IV: Multiple extranodal sites

Pathophysiology

B and T cells have different stages of development. Accumulation of multiple genetic lesion affecting proto-oncogenes and Tumour Suppressor Genes (TGS) during stages of lymphocyte development leads to Lymphoma

B cell Lymphoma

Majority of B cell lymphomas are derived from germinal center or post-germinal center B-cells
Major genetic modifications occur during the normal germinal center reaction of B cells
These changes (class-switch recombination and somatic hypermutation) are required for normal immune development, but also place the cell at risk of acquiring additional mutations that may be oncogenic

T cell Lymphoma

Majority of T cell lymphomas are derived from post-thymic T cells.
Gene rearrangement of T cell receptors (TCRs) is essential for the development of a highly diverse repertoire of TCRs required for an effective immune system, but also places the cell at risk for acquiring potentially oncogenic chromosomal translocations.