Lymphoma Main Categories
Follicular Lymphoma Clinical Features
4 listed
- Painless generalized lymphadenopathy is common
- incurable and indolent clinical course except when transformed
- histologic transformation occurs in up to half of the cases
- Diffuse large B-cell lymphoma is the most common type of transformation but can also become Hodgkins Lymphoma
Most common indolent type of Non-Hodgkin Lymphoma in the US
Follicular Lymphoma
Follicular Lymphoma Morphological Features
5 listed
- Nodular growth pattern
- closely arranged neoplastic follicles
- Neoplastic cells include:
- Small cleaved lymphocytes (centrocytes)
- Large lymphocytes (centroblasts)
Follicular Lymphoma Cells arise from?
Germinal Center B-cells
Follicular Lymphoma Neoplastic Cells
2 listed
- Small cleaved lymphocytes (Centrocytes)
- Large Lymphocytes (Centroblasts)
Follicular Lymphoma Histology
look like germinal center cells
Neoplastic vs Reactive Follicles: Reactive Follicle Features
4 listed
- Reactive Follicle:
- Intact mantle zone
- Many ‘tingible body’ macrophage
- polarization is present
Neoplastic vs Reactive Follicles: Neoplastic Follicle Features
3 listed
- Absent or thin Mantle Zone
- Lack of ‘tingible body’ macrophages
- lack of polarization
Identify
Reactive Follicle
Tingible Body Macrophages
beig macrophages with lots of debris
present in a reactive follicle
Absent in neoplastic follicle
Follicular Lympha Flow Cytometry
- Small cells
- CD19+ CD20+ and CD10+ (germinal center like)
- Monoclonal so either kappa or lambda
Follicular Hyperplasia Flow Cytometry
- small cells
- few CD10+ germinal center cells
- B cells are not monoclonal
Follicular Lymphoma Genetics
t(14;18)(q32;q21)
- present in 90% of follicular lymphomas
- Balanced reciprocal translocation
- BCL2 oncogene on chromosome 18 is juxtaposed to IGH gene on chromosome 14
- Results in upregulation of BCL2 gene
Follicular Lymphoma specific mutation
Follicular Lymphoma Genetic testing
t(14;18)(q32;q21) can be seen in karyotype
or FISH
Follicular Lymphoma Pathophysiology
3 listed
consequences of BCL2/IGH rearrangement
Follicular Lymphoma Immunohistiochemistry
- Reactive follicles never express BCL2
- Only neoplastic germinal centers express BCL2 in 90% of them
Mantle Cell Lymphoma prevalence
2.5% of Non-Hodgkin Lymhoma
Mantle Cell Lymphoma Clinical Presentations
- commonly present with painless lymphadenopathy
- Frequent extranodal involvement including BM, spleen, liver and GI tract
- intestinal involvement may present with polyps (lymphomatoid polyposis)
Mantle Cell Lymphoma Prognosis
4 listed
- Very aggressive
- Poor prognosis
- median survival 3-4 years
- Currently incurable
Mantle Cell Lymphoma Cells come from?
Mantle Cell Lymphoma Morphologic Features
Mantle Cell Lymphoma Immunophenotype
4 listed
- CD19+
- CD20+
- CD5+ (usually T cell marker)
- Cyclin D1+
Mantle Cell Lymphoma Genetics
t(11;14)(q13;q32)
Mantle Cell Lymphoma Pathophysiology
- CCD1 (Cyclin D1) gene juxtaposed to the IGH gene resulting in upregulation of the gene
- The upregulated CCND1 gene results in overexpression of cyclin D1
Mantle Cell Lymphoma Genetic testing
- Karyotype
- FISH
Mantle Cell Lymphoma Immunohistochemistry
Role of Cyclin D1 in cell cycle
passes G0 to S
Marginal Zone Lymphoma Follicle Histology
Arise from memory B cells in the marginal zone
Marginal Zone Lymphoma Morphology
MALT Lymphoma Associations
2 listed
Helicobacter pylori associations with lymphoma
MALT Lymphoma Clinical Course
MALT Lymphoma Immunophenotype
4 listed
- CD19+
- CD20+
- CD5-
- CD10-
Burkitt Lymphoma Types
3 listed
- Endemic in Africa all EBV+
- Sporadic
- Immunodeficiency-related (HIV)
Burkitt Lymphoma Histology
Identical histology in all types Starry-sky
Burkitt Lymphoma Immunophenotype
4 listed
- CD20+
- CD10+
- BCL6+
- BCL2-
Burkitt Lymphoma Genetics
3 listed
- t(8;14) in 80%
- t(2;8) or t(8;22) in 20%
Burkitt Lymphoma Endemic type and lymphoma belt of Africa
Fastest growing tumor
Burkitt Lymphoma
Burkitt Lymphoma Molecular Pathogenesis
t(8;14)(q24;32) in 80% of cases
- MYC gene on chromosome 8 is juxtaposed to the IGH locus on chromosome 14
- The breakpoints in IGH locus in endemic occurs within or in proximity to JH region
- The breakpoints in IGH locus in sporadic and HIV-associated Burkitt Lymphomas involve class switching regions
BurkitBurkitt Lymphoma genetic testing
Karyotype and FISH
Burkitt Lymphoma Pathophysiology
All translocations result in MYC gene upregulation and the consequences are:
- promote cell cycle entry
- block differentiation
- Stimulate cell proliferation
- increase cellular metabolism
- Induce apoptosis in the absence of adequate growth support
Clinical & Diagnostic utility of detection of specific chromosomal rearrangements
3 listed
The significance of distinction of subtypes of B-cell lymphoma
Antigen receptor gene rearrangements
Light and Heavy chain rearrangements
- this process involves chromosomal breaking and rejoining and errors can occur during this process
- The antigen receptor genes serve as a second set of tumor markers in lymphoid neoplasms
- Antigen receptor gene rearrangements in lymphoid cells occur often before clonal expansion
Clinical and diagnostic utility of IGH gene rearrangements
3 listed
PCR can identify clonal populations
Polyclonal vs monoclonal populations capillary electrophoresis
Question 1
Mantle Cell Lymphoma
Question 2
Mantle Cell Lymphoma
C
- CD10+
- CD20+
- CD5+
- Cyclin D1+
Summary of Selected Mature B Cell Lymphomas
Indolent Lymphomas Treatment
- incurable in an advanced stage
- Treat only symptomatic Disease
- Rituximab + Chemotherapy
Aggressive Lymphomas Treatment
- Rapidly fatal if untreated but is curable
- Treated aggressively at diagnosis - chemo + Rituximab
Mantle Cell Lymphomas Treatment
Treated according to patient tolerance
MALT Lymphomas Treatment
Triple Antibiotic therapy if localized disease
Indolent lymphomas
- Follicular Lymphoma
- Marginal Zone Lymphoma
Aggressive Lymphomas
2 listed
- Burkitt Lymphoma
- DLBCL