Non-Hodgkin's Lymphoma Flashcards
NHL Subtypes by Prognosis
- Aggressive NHL (high grade)
*60% of NHL
*diffuse large B-cell lymphoma
*potentially curable, responds to chemotherapy
- Indolent NHL (low grade)
*40% of NHL
*follicular lymphoma
*Often not curable
*can sometimes transform into aggressive form
- Intermediate grade
*somewhere in b/w
Non-Hodgkin Lymphoma Stage
- Stage I
*localized disease; single lymph node region or single organ
- Stage II
*2 or more lymph node regions on the same side of the diaphragm
- Stage III
*2 or more lymph node regions above and below the diaphragm
- Stage IV
*widespread disease; multiple organs, w/ or w/o lymph node involvement
Immune Cell Antigens Detected by Monoclonal Antibodies
Primarily T-Cell Assoc.
- CD3; Thymocytes, mature T cells
- CD5; T cells and a small subset of B cells
Primarily B-Cell Assoc.
- CD10; Pre-B cells and germinal-center B cells
- CD20; Pre-B cells after CD19 and mature B cells but not plasma cells
- CD23; Activated mature B cells
Primarily Monocyte or Macrophage Assoc.
- CD15; Granulocytes; Reed-Sternberg cells and variants
Activation Markers
- CD30; Activated B cells, T cells, and monocytes; Reed-Sternberg cells and variants
Somatic Hypermutation
- Important normal immune process
- Creates point mutations within Ig genes that may increase antibody affinity for antigen
- Advantageous mutations lead to a larger pop. of these specialized lymphocytes
- Helps fight infections better
B-Symptoms
- Assoc. w/ NHL
- Fever, night sweats, and unintentional weight loss
- Lymph nodal/splenic/other enlargement
Origin of Lymphomas
- B lymphocytes (B cells)
- T lymphocytes (T cells)
- Natural killer (NK) cells
How Do Lymphomas Form?
- Chromosomal translocations
*Involved genes are involved in the development, growth, or survival of the normal counterpart of the malignant cell
*Oncoproteins created by mutations block normal maturation, turn on pro-growth signaling pathways, or protect cells from apoptotic cell death
Lymphoid Malignancy and Infection
- Epstein Barr: Burkitt’s, Hodgkin’s
- HTLV-1: Adult T-cell leukemia/lymphoma
- H. pylori: Gastric lymphoma
How do lymphomas form?
- Chronic inflammation
*H. pylori and gastric B-cell lymphoma
*Gluten-sensitive enteropathy and intestinal T-cell lymphomas
- Iatrogenic factors
*Radiation
*Chemotherapy
*Chemical-Agent Orange
- Smoking
*Carcinogens in tobacco smoke
Hodgkin’s vs. Non-Hodgkin’s Epidemioly Chart
Hodgkin’s vs. Non-Hodgkin’s Lymphoma Clinical Presentation
Small Lymphocytic Lymphoma (SLL)
- Tissue version of CLL
- Cell of origin: antigen-naive B-lymphocytes
- Immunophenotype: CD20 (B-cell marker), CD5 and CD23 (fairly specific combination for CLL/SLL)
- Genotype: Tisomy 12, deletions of 11q, 13q, and 17p
- Clinical features: Indolent (slow growing, not curable), lymphocytosis, lymphadenopathy
- Smudge cells; Important lab feature: cells of CLL/SLL are more friable and tend to break upon preipheral blood smear preparation
Follicular Lymphoma (FL)
- Cell of origin: Germinal center B-cell
- Immunophenotype: CD20+, CD10+, bcl-2+
*neoplastic cells express CD20 (B-cell marker), CD10 (germinal center marker) and bcl-2 (anti-apoptotic marker-abnormal in germinal centers)
- Genotype: t(14;18)
- Clinical features: older adults, lymphadenopathy, BM involvement, widespread at diagnosis, often asymptomatic
Follicular Lymphoma (FL) Genetic Abnormality
- BCL-2/IgH Translocation
*BCL-2 on chromosome 18 and IgH locus on chromosome 14
*constitutive expression of BCL-2 protein
*inhibition of apoptosis- survival advantage
Mantle Cell Lymphoma (MCL)
- Cell of origin:
- Immunophenotype: CD20+, CD5+
- Molecular:
*overexpression of cyclin D1 (a protein that stimulates cell growth)
*translocation t(11;14)
- Clinical features: Usually begins w/ lymph node enlargement- can involve BM, liver, GI tract, more aggressive than CLL/SLL
