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Heme / Onc > SM_264b: Lymphoid Histology and B Cell Lymphomas > Flashcards

SM_264b: Lymphoid Histology and B Cell Lymphomas Flashcards

1
Q

This is ___

A

Normal lymph node

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2
Q

Lymph node is composed of ____, ____, ____, ____, and ____

A

Lymph node is composed of

  • Follicle
  • Marginal zone
  • Medulla
  • Paracortex
  • Sinus
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3
Q

____ of lymph node

A

Follicles of lymph node

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4
Q

____ of lymph node

A

Marginal zone of lymph node

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5
Q

____ of lymph node

A

Paracortex of lymph node

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6
Q

____ of lymph node

A

Medulla of lymph node

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7
Q

Follicle of lymph node consists of ___ and ___

A

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)
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8
Q

Marginal zone of lymph node is ___

A

Marginal zone of lymph node is memory B cells

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9
Q

Medulla is ___

A

Medulla is B cell area (accumulation of plasma cells)

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10
Q

Paracortex of lymph node is ___ and ___

A

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

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11
Q

Sinus of lymph node is ___

A

Sinus of lymph node is macrophage area (sieve functions)

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12
Q

B lymphocytes are located in ___ of lymph node

A

B lymphocytes are located in cortex of lymph node

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13
Q

Diagnosis of lymphoma involves ____, ____, ____, and ____

A

Diagnosis of lymphoma involves architecture, cytology, immunophenotype, and molecular

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14
Q

Benign follicles are ___, ___, and ___

A

Benign follicles are variable, polarized, and have mantle zone intact

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15
Q

Neoplastic follicles are ____, ____, and ____

A

Neoplastic follicles are crowded, loss of polarity, and have attenuated mantle zone

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16
Q

Describe lymphoma cytology

A

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
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17
Q

Describe immunohistochemistry

A

Immunohistochemistry

  • Detecting antigen in cells of a tissue section
  • Antibodies bind specifically to antigen
  • Molecular markers are characteristic of particular cellular components
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18
Q

CD45 is marker for ___

A

CD45 is marker for all leukocytes

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19
Q

CD20 and PAX5 are markers for ___

A

CD20 and PAX5 are markers for B cells

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20
Q

CD3 is marker for ___

A

CD3 is marker for T cells

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21
Q

CD4 is marker for ___, while CD8 is marker for ___

A

CD4 is marker for helper T cells, while CD8 is marker for cytotoxic T cells

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22
Q

CD10 is marker for ___

A

CD10 is marker for germinal center B cells

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23
Q

CD23 is marker for ___

A

CD23 is marker for follicular dendritic cells

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24
Q

Ig (kappa / lambda) is marker for ___

A

Ig (kappa / lambda) is marker for plasma cells

25
Q

Follicular dendritic cell in germinal center is ___

A

Follicular dendritic cell in germinal center is CD21+

26
Q

Germinal center B cells are ____, ____, and ____

A

Germinal center B cells are CD20+, CD10+, and BCL6+

27
Q

Interfollicular T cells are ___

A

Interfollicular T cells are CD3+

28
Q

Describe neoplastic follicles

A

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)
29
Q

Monotypic immunoglobulin light chain expression pattern suggests ____

A

Monotypic immunoglobulin light chain expression pattern suggests a clonal B cell population

  • Polytypic kappa / lambda expression in normal B lymphocytes
30
Q

Clonal IgH rearrangement is ___

A

Clonal IgH rearrangement is abnormal

31
Q

Some lymphomas are associated with ____ that can be detected with ____

A

Some lymphomas are associated with specific chromosomal translocations that can be detected with chrosomal analysis and FISH

32
Q

Describe categories of lymphoma

A

Lymphoma

  • Precursor lymphoid neoplasm
  • Mature lymphoid neoplasm
    • Non-Hodgkin lymphoma: B cell type, T / NK cell type
    • Hodgkin lymphoma
33
Q

Describe staging of malignant lymphoma

A

Staging of malignant lymphoma

  1. Determine extent of disease / dissemination: non-invasive, invasive
  2. Influences therapy
    1. Some stage I / IIA: radiotherapy
    2. Some stage I/ IIB / III / IV: chemotherapy
34
Q

Describe Ann Arbor staging system for lymphoma

A

Ann Arbor staging system for lymphoma

  1. Single lymph node region or extranodal site
  2. ≥ 2 lymph node regions (or one extranodal site and ≥ 1 lymph node regions) on same side of diaphragm
  3. Lymph node regions (or extranodal sites and lymph nodes) on both sides of diaphragm
  4. Any previous with additional extranodal site or ≥ 2 extranodal sites with lymph nodes
35
Q

Prognosis of B cell lymphoma is primarily based on ___ and ___

A

Prognosis of B cell lymphoma is primarily based on inherent biology of tumor and stage

36
Q

Describe follicular lymphomas

A

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
37
Q

Follicular lymphomas are associated with ___

A

Follicular lymphomas are associated with t(14;18) translocation

  • Fuse BCL2 with IGH promoter -> increase expression of anti-apoptotic BCL2 gene
38
Q

Describe follicular lymphoma morphology

A

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)
39
Q

Describe treatment and prognosis of follicular lymphoma

A

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
40
Q

Describe diffuse large B cell lymphoma

A

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
41
Q

Describe diffuse large B cell lymphoma pathogenesis

A

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
42
Q

Describe diffuse large B cell lymphoma morphology

A

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
43
Q

Describe treatment and prognosis of diffuse large B cell lymphoma

A

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
44
Q

Describe clinical characteristics of chronic lymphocytic leukemia / small lymphocytic lymphoma

A

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
45
Q

Describe CLL/SLL pathogenesis

A

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
46
Q

Describe CLL/SLL morphology

A

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
47
Q

Describe CLL/SLL treatment and prognosis

A

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)
48
Q

Describe mantle cell lymphoma

A

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
49
Q

Describe mantle cell lymphoma pathogenesis

A

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
50
Q

Describe mantle cell lymphoma morphology

A

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
51
Q

Describe mantle cell lymphoma treatment and prognosis

A

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
52
Q

Describe extranodal marginal zone lymphoma

A

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
53
Q

Describe extranodal marginal zone lymphoma pathogenesis

A

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
54
Q

Describe extranodal marginal zone lymphoma morphology

A

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
55
Q

Describe Burkitt lymphoma

A

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
56
Q

Describe Burkitt lymphoma pathogenesis

A

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
57
Q

Describe Burkitt lymphoma morphology

A

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)
58
Q

Mantle cell lymphoma has ___

A

Mantle cell lymphoma has t(11;14)

  • IgH/CCND1
59
Q

Follicular lymphoma has ____

A

Follicular lymphoma has t(14;18)

  • BCL2/IgH

Heme / Onc (41 decks)

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