Non-Hodgkin’s Lymphoma:
This is a very heterogeneous group of malignancies of the lymphoid glands, and other lymphatic tissue, e.g. the spleen and bone marrow. But all organs contain lymphoid tissue, and one can see lymphomas involving the stomach, testicles, skin, oral cavity and central nervous system.
Risk Factors and Causative Factors: Are linked to
-Viruses, e.g. EBV, HTLV-1, hepatitis C virus,
-Environment: occupations using chemicals like pesticides and herbicides and solvents like farmers, pesticide applicators, chemists, painters, and machinists.
-Previous chemotherapy or radiation therapy.
-Immune deficient states, either Congenital or acquired, like HIV disease
-Chromosomal abnormalities.
Classifications: are a constant work in progress. Broadly, the subtypes fall into 3 groups:
Low Grade Lymphomas: include small lymphocytic lymphoma, Follicular small cleaved cells, and follicular mixed variety. These mainly present with waxing and waning lymph node enlargement. These behave in an indolent manner, and do not require immediate treatment.
Intermediate Grade, which includes Follicular large cell, diffuse small cleaved, diffuse mixed small and large cell, and diffuse large cell. B symptoms are common, as well as disease outside the lymph node areas like the GI tract, skin, CNS, sinuses and thyroid
High Grade includes Lymphoblastic lymphoma, Burkitt’s lymphoma and Immunoblastic Lymphoma.
Other systems of classification go by dividing them by cell of origin: T cell, B cell, and NK cell.
Diagnosis: involves careful history taking and physical examination.
-Excisional biopsy of an enlarged lymph node. Fine needle aspirations are not enough, since diagnosis require description of the pattern of involvement (diffuse vs. follicular). This can only be obtained by getting a whole sample, either by a core biopsy or excision.
-CT scans of the chest/ abdomen/ pelvis + baseline PET scan
-Bone marrow biopsy
-Blood tests for a CBC, Sedimentation rate, LDH, liver panel and B2 microglobulin.
-Viral testing for specific subtypes of lymphoma, e.g. HIV
-Spinal fluid analysis for specific subtypes, which tend to travel to the Central Nervous System.
-Examination of the GI tract in lymphomas of the throat lining.
Staging: depends on the number of lymph nodes involved, involvement of the spleen, and/ or a non lymphatic site
Prognosis: depends on the kind of lymphoma and stage. Slow growing, low-grade lymphomas can do well for many years, even without treatment. High-grade lymphomas need urgent, aggressive treatment, as their survival can be measured in weeks. There is an International Prognostic Index, which assigns a score, depending on age, LDH, Performance Status, Stage and number of extra or Non-Nodal sites of involvement. Cytogenetic abnormalities and tumor proliferation markers also predict behavior.
Treatment is mainly combinations of chemotherapy, depending on the nature of the lymphoma, and the need for aggressive intervention.
Common combinations include CVP-R: Cytoxan-Vincristine-Prednisone- Rituximab given every 21 days, CHOP-R: Cytoxan, Doxorubicin, Vincristine, Prednisone + Rituximab every 21 days, FC-R: Fludarabine-Cytoxan+ Rituximab, Bendamustine + Rituximab, etc., etc. The addition of Rituximab, which is an antibody preparation, both to the main combination, and as a maintenance treatment afterwards has added significantly to cure rates.
Radiation can be used in early stage low-grade disease.
Stem cell transplantation is used for salvage therapy as well as for management of aggressive, poor risk disease in first remission.
CNS prophylaxis may be required for high-risk areas, or high-risk histologies. This can involve giving chemotherapy directly into the spinal fluid space, or by weaving High Dose Methotrexate into the chemotherapy regimen. High dose Methotrexate penetrates the blood brain barrier to confer protection.