SM_264b: Lymphoid Histology and B Cell Lymphomas Flashcards
This is ___
Normal lymph node
Lymph node is composed of ____, ____, ____, ____, and ____
Lymph node is composed of
- Follicle
- Marginal zone
- Medulla
- Paracortex
- Sinus
____ of lymph node
Follicles of lymph node
____ of lymph node
Marginal zone of lymph node
____ of lymph node
Paracortex of lymph node
____ of lymph node
Medulla of lymph node
Follicle of lymph node consists of ___ and ___
Follicle of lymph node consists of mantle zone and germinal center
- Mantle zone: naive cells meet antigen
- Germinal center: proliferating cells (centroblasts) differentiate into antigen-specific B cells (centrocytes)
Marginal zone of lymph node is ___
Marginal zone of lymph node is memory B cells
Medulla is ___
Medulla is B cell area (accumulation of plasma cells)
Paracortex of lymph node is ___ and ___
Paracortex of lymph node is maInly T cell area and site of entrance of all lymphoid cells and accessory cells for T / B cell interaction
Sinus of lymph node is ___
Sinus of lymph node is macrophage area (sieve functions)
B lymphocytes are located in ___ of lymph node
B lymphocytes are located in cortex of lymph node
Diagnosis of lymphoma involves ____, ____, ____, and ____
Diagnosis of lymphoma involves architecture, cytology, immunophenotype, and molecular
Benign follicles are ___, ___, and ___
Benign follicles are variable, polarized, and have mantle zone intact
Neoplastic follicles are ____, ____, and ____
Neoplastic follicles are crowded, loss of polarity, and have attenuated mantle zone
Describe lymphoma cytology
Cytology
- Normal: mixed population
- Diffuse large B cell lymphoma: large cells, vesicular chromatin, nucleoli
- Mantle cell lymphoma: medium sized cells, condensed chromatin, cleaved nuclei
- Small lymphocytic lymphoma: small cells, condensed chromatin
Describe immunohistochemistry
Immunohistochemistry
- Detecting antigen in cells of a tissue section
- Antibodies bind specifically to antigen
- Molecular markers are characteristic of particular cellular components
CD45 is marker for ___
CD45 is marker for all leukocytes
CD20 and PAX5 are markers for ___
CD20 and PAX5 are markers for B cells
CD3 is marker for ___
CD3 is marker for T cells
CD4 is marker for ___, while CD8 is marker for ___
CD4 is marker for helper T cells, while CD8 is marker for cytotoxic T cells
CD10 is marker for ___
CD10 is marker for germinal center B cells
CD23 is marker for ___
CD23 is marker for follicular dendritic cells
Ig (kappa / lambda) is marker for ___
Ig (kappa / lambda) is marker for plasma cells
Follicular dendritic cell in germinal center is ___
Follicular dendritic cell in germinal center is CD21+
Germinal center B cells are ____, ____, and ____
Germinal center B cells are CD20+, CD10+, and BCL6+
Interfollicular T cells are ___
Interfollicular T cells are CD3+
Describe neoplastic follicles
Neoplastic follicles
- Abnormal immunoarchitecture: CD20 outside of follicles
- Aberrant expression of proteins: expression of BCL-2 in neoplastic germinal centers in follicular lymphoma with t(14;18)
Monotypic immunoglobulin light chain expression pattern suggests ____
Monotypic immunoglobulin light chain expression pattern suggests a clonal B cell population
- Polytypic kappa / lambda expression in normal B lymphocytes
Clonal IgH rearrangement is ___
Clonal IgH rearrangement is abnormal
Some lymphomas are associated with ____ that can be detected with ____
Some lymphomas are associated with specific chromosomal translocations that can be detected with chrosomal analysis and FISH
Describe categories of lymphoma
Lymphoma
- Precursor lymphoid neoplasm
- Mature lymphoid neoplasm
- Non-Hodgkin lymphoma: B cell type, T / NK cell type
- Hodgkin lymphoma
Describe staging of malignant lymphoma
Staging of malignant lymphoma
- Determine extent of disease / dissemination: non-invasive, invasive
- Influences therapy
- Some stage I / IIA: radiotherapy
- Some stage I/ IIB / III / IV: chemotherapy
Describe Ann Arbor staging system for lymphoma
Ann Arbor staging system for lymphoma
- Single lymph node region or extranodal site
- ≥ 2 lymph node regions (or one extranodal site and ≥ 1 lymph node regions) on same side of diaphragm
- Lymph node regions (or extranodal sites and lymph nodes) on both sides of diaphragm
- Any previous with additional extranodal site or ≥ 2 extranodal sites with lymph nodes
Prognosis of B cell lymphoma is primarily based on ___ and ___
Prognosis of B cell lymphoma is primarily based on inherent biology of tumor and stage
Describe follicular lymphomas
fzollicular lymphomas
- 25-30% of non-Hodgkin’s lymphoma
- Cell of origin: germinal center B cell
- Older individuals (> 50) and rare in kids
- Painless generalized lymphadenopathy: marrow involvement at diagnosis is common
Follicular lymphomas are associated with ___
Follicular lymphomas are associated with t(14;18) translocation
- Fuse BCL2 with IGH promoter -> increase expression of anti-apoptotic BCL2 gene
Describe follicular lymphoma morphology
Follicular lymphoma morphology
- Nodular proliferation
- Neoplastic cells are centrocytes admixed with centroblasts
- Centroblasts predominantly correlate with more aggressive clinical course
- Neoplastic cells express CD20, B cell markers, and germinal center B cell markers (CD10, BCL6)
Describe treatment and prognosis of follicular lymphoma
Follicular lymphoma treatment and prognosis
- Observation
- Chemo
- Antibody against CD20 and BCR signaling inhibitor
- 30-40% of patients progress to diffuse large B cell lymphoma
Describe diffuse large B cell lymphoma
Diffuse large B cell lymphoma
- Most common type
- Adults > 50 years but constitutes 15% of childhood lymphoma
- Presents with a rapidly enlarging symptomatic mass at one or several sites
- Can arise in any organ or tissue
Describe diffuse large B cell lymphoma pathogenesis
Diffuse large B cell lymphoma pathogenesis
- Most common genetic events are chromosomal translocations that lead to over-expression of several oncogenes
- BCL2: t(14;18), BCL2/IgH translocation in 30%, some represent transformation from follicular lymphoma
- BCL6: rearrangement or mutation, 1/3 of cases
- MYC: 5-10% have rearrangement in MYC a transcriptional factor that regulates cell growth
Describe diffuse large B cell lymphoma morphology
Diffuse large B cell lymphoma morphology
- Neoplastic cells are large (3-4x size of normal lymphocytes)
- Variable morphology (round / oval, single / multiple nucleoli, variable cytoplasm, rare anaplastic or Reed-Sternberg like)
- Tumor cells express CD20 with variable CD10, BCL6, BCL2, and MYC
Describe treatment and prognosis of diffuse large B cell lymphoma
Diffuse large B cell lymphoma treatment and prognosis
- Progressive and fatal without treatment
- Treat with intensive combination chemo and anti-CD20
- Remission in 60-80% of patients
- Stem cell transplant offered to patients with refractory / relapsed disease
Describe clinical characteristics of chronic lymphocytic leukemia / small lymphocytic lymphoma
Chronic lymphocytic leukemia / small lymphocytic lymphoma clinical chracteristics
- Identical but differ in extent of peripheral blood involvement
- Often asymptomatic with enlarged lymph nodes
- If blood neoplastic cells exceed 5000/uL it is CLL
- Most common leukemia of adults in western world
Describe CLL/SLL pathogenesis
CLL/SLL pathogenesis
- Indolent and slowly growing: increased cell survival
- High level of BCL2 (a protein that inhibits apoptosis)
- Abnormal B-cell receptor signaling (BTK / NFKB pathway) increases cell survival
- Abnormal immune function: patients often have hypoglobulinemia and some have autoantibodies
Describe CLL/SLL morphology
CLL/SLL morphology
- Blood: increased number of small mature appearing lymphocytes with condensed chromatin
- Marrow, spleen, and liver involved in almost all cases
- Lymph node is effaced by sheets of small lymphocytes
- Neoplastic cells express CD20 (variable) and CD5
Describe CLL/SLL treatment and prognosis
CLL/SLL treatment and prognosis
- Generally indolent
- May not need treatment
- Symptomatic patients can be treated with antiboides against CD20 and i inhibitors BCL2
- Presence of TP53 mutation portends worse prognosis
- Small fraction transform to diffuse large B cell lymphoma (Richter transformation)
Describe mantle cell lymphoma
Mantle cell lymphoma
- Cell of origin: naive B cells in mantle zone of lymphoid follicles
- Men ≥ 50
- Presents with fatigue and lymphadenopathy
- Generalized disease involving lymph nodes, bone marrow, spleen, liver, GI tract
Describe mantle cell lymphoma pathogenesis
Mantle cell lymphoma pathogenesis
- Strongly associated with t(11;14) translocation
- Fuse cyclin D1 with IGH promoter
- Overexpession of cyclin D1 drives cell growth: cyclin D1 is part of cyclin-dependent kinase complex that promotes cell cycle progression from G1 to S phase
Describe mantle cell lymphoma morphology
Mantle cell lymphoma morphology
- Lymph nodes are effaced by tumor cells growing in diffuse or nodular patterns
- Tumor cells are intermediate in size with irregular nuclear contours
- Tumor cells express CD20, CD5, and cyclin D1
- Proliferation rate by Ki67 is important prognostic marker
Describe mantle cell lymphoma treatment and prognosis
Mantle cell lymphoma treatment and prognosis
- Moderately aggressive
- Treat with chemo, antibody against CD20, and BCR signaling inhibitor
- Median survival is 4 to 6 years
Describe extranodal marginal zone lymphoma
Extranodal marginal zone lymphoma
- Presents as swelling of salivary gland, thyroid, orbit or discovered in H. pylori induced gastritis
- Can be curred by simple excision followed by radiotherapy or antibiotics for H. pylori infection when localized
Describe extranodal marginal zone lymphoma pathogenesis
Extranodal marginal zone lymphoma pathogenesis
- Indolent lymphoma arises within and sustained by chronic inflammation
- Most often in tissues inflamed due to chronic inflammation or autoimmune disorder
- Cell of origin: antigen-stimulated B cells
- Disease may start from polyclonal immune reaction with subsequently acquired driver mutations
- Neoplastic clone emerges and may need environmental signal to sustain growth and survival
Describe extranodal marginal zone lymphoma morphology
Extranodal marginal zone lymphoma morphology
- Clonal B-cells infiltrate epithelium of involved tissue: lymphoepithelial lesion
- Small lymphocytes with abundant cytoplasm or exhibit plasma cell differentiation
- Neoplastic B cells express CD20 and other markers and are CD5- and CD10-
- Gastric cases may have H. pylori infection
Describe Burkitt lymphoma
Burkitt lymphoma
- Endemic form: Africa, maxillary or mandibular masses, EBV associated
- Sporadic form: other parts of the world, involving bowel / retroperitoneum / ovaries
- Immunodeficiency related form
- Present as rapidly growing masses (fastest growing human tumor)
- Most patients can be cured with intensive chemo
Describe Burkitt lymphoma pathogenesis
Burkitt lymphoma pathogenesis
- Translocation involving MYC (chromosome 8) with IGH (chromosome 14), IGK (chromosome 2), and IGL (chromosome 22)
- MYC: oncogene plays a role in cell cycle progression, apoptosis, and cellular transformation
- Latently infected with EBV
Describe Burkitt lymphoma morphology
Burkitt lymphoma morphology
- Starry sky pattern: lymphocytes admixed with phagocytic macrophages with cellular debris (high cellular turnover)
- Intermediate in size, round / oval cells with basophilic cytoplasm and cytoplasmic vacuole
- Tumor cells express CD20, germinal center B cell markers (CD10, BCL6, and MYC)
Mantle cell lymphoma has ___
Mantle cell lymphoma has t(11;14)
- IgH/CCND1
Follicular lymphoma has ____
Follicular lymphoma has t(14;18)
- BCL2/IgH
