14. Non-Hodgkin's Lymphomas. Diffuse Large B-cell Lymphoma

Essay 14- Non-Hodgkin’s Lymphomas. Diffuse Large B-Cell Lymphoma

Definition of lymphoma

• Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and other lymphoid tissue

Definition of NH lymphomas

• Large group of clonal lymphoid tumours!
• About 85% of B cell and 15% of T or NK cell origin

Etiology

• NHL is associated with various factors:
• Infections- EBV, HTLV-1, HEP C, H.pylori infection
• Environmental factors
• Immunodeficiency states
• Chronic inflammation
• Drugs- phenytoin, digoxin, TNF antagonists
• Autoimmune disorders- SLE, RA, Sjögren syndrome, Hashimoto thyroiditis

Pathophysiology

• Non-Hodgkin lymphoma arises either from B cells, T cells, or NK cells due to chromosomal translocation or mutation/deletion
• Proto-oncogenes are activated by chromosomal translocation, and tumor suppressor genes are inactivated by chromosomal deletion or mutation
• The t(14;18) translocation is the most common chromosomal abnormality in NHL

Classification of NHL

Clinical features of NHL

• Superficial lymphadenopathy- asymmetric, painless enlargement of LN
• Constitutional symptoms- fever, night sweats, oropharyngeal involvement
• Symptoms due to anemia
• Infections due to neutropenia
• Abdominal disease

Diagnosis

• LN biopsy:
• It is definitive investigation!
• For B-cell lymphomas, expression of either κ or λ light chains confirms clonality and distinguishes the disease from a reactive node
• Labs:
• In advanced disease- anemia, neutropenia, thrombocytopenia
• Lymphoma cells may be found in peripheral blood
• LDH is raised
• Cytogenetics:
• Burkitts lymphoma t(8; 14)
• Follicular lymphoma t(14;18)
• Mantle cell lymphoma t(11;14)
• Anaplastic large cell lymphoma t(2; 5)
• Imaging- CT, PET, MRI (maybe)
• Immunoglobulin electrophoresis may reveal paraprotein
• HIV status testing as indicated

General principles of treatment

• Treatment is started in the form of a combination of chemotherapy with monoclonal antibodies against the tumour cell
• Monoclonal antibody therapy- 85% are B cell origin, anti-CD20 antibodies have proven to benefit
• Rituximab- IV or SC administration
• Ofatumumab
• Some new drugs have been developed:
• Oral agents that block activity of the BTK or PI3KD proteins, as used for B-CLL (see p. 201)
• Drugs that inhibit BCL-2 activity
• Drugs that block activity of kinases, such as ALK which is increased in patients with anaplastic large cell lymphoma.