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MOD 3 > Lymphoid Neoplasms > Flashcards

Lymphoid Neoplasms Flashcards

1
Q

What are the three types of lymphoid neoplasms

A

B-cell, T-cell, and NK-cell origin

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2
Q

Major difference between leukemia and lymphoma

A

Leukemia: bone marrow and peripheral blood (ex: acute lymphoblastic leukemia, chronic lymphocytic leukemia)

Lymphoma: discrete tissue masses

  • lymph node (ex. diffuse large B-cell lymphoma
  • extranodal (ex. MALT lymphoma of stomach)

Note: in reality, theres so much overlap (i.e. lymphomas can spill into the blood “leukemic phase”)

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3
Q

Site of origin for lymphoid tissue neoplasms (4)

A
  1. lymph node
  2. spleen
  3. thymus
  4. bone marrow

(and other sites)

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4
Q

What are the four things you must integrate for a diagnosis, according to WHO classification

A
  1. morphologic
  2. immunophenotypic
  3. genetic
  4. clinical
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5
Q

WHO classifications of lymphoi neoplasms (5)

  1. Precursor B-cell neoplasm
  2. Peripheral B-cell neoplasm
  3. Precursor T-cell neoplasm
  4. Peripheral T-cell neoplasm
  5. Hodgkin lymphoma
A
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6
Q

Two most frequent lymphoma types

A

DLBCL (30%)

Follicular Lymphoma (20%)

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7
Q

6 main etiologies and pathogenesis of lymphoma

A
  1. acquired genetic abnormalities (chromosomal translocations, other mutations)
  2. inherited genetic abnormalities
  3. viruses
  4. chronic inflammation
  5. iatrogenic factors (from medical treatment)
  6. smoking
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8
Q

Abnormal monoclonal (neoplastic)

antigen receptor gene rearrangement

A

express same antigen receptor

IgH, TCR

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9
Q

4 diagnostic tools

A
  • Morphology (light microscopy)
  • Immunophenotyping
  • cytogenetics/FISH
  • molecular diagnostics (PCR)
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10
Q

What are the two subsets of morphology (light microscopy) as a diagnostic tool?

A
  • Patterns
    • follicular/architecture (e.g. follicular lymphoma)
    • diffuse patterns (eg. diffuse large B cell lymphoma)
  • Cytology
    • small cells (eg. CLL/SLL)
    • large cells (eg. DLBCL)
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11
Q

2 subsets of immunophenotyping

A

1) immunohistochemistry
2) flow cytometry

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12
Q

lymphoid progenitor markers (3)

A

Tdt

CD34

HLA-Dr

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13
Q

Pre-B markers (6)

A

CD19

CD20

CD10

Dr

Tdt

cig

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14
Q

mature B cell markers (3)

A

CD19

CD20

slg

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15
Q

plasma cell makers (2)

A

CD138

CD38

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16
Q

Important T cell markers (before differentiating into mature cytotoxic and helper T cells)

A

CD1-CD8

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17
Q

Mature Cytotoxic T cell marker

Mature Helpter T cell marker

A

cytotoxic: CD8
helper: CD4

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18
Q

Which is the most common cancer in children

A

Acute Lymphoblastic Leukemia (ALL)

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19
Q

ALL has symptoms similar to AML. What are 4 exceptions?

A

In ALL:

  1. lymphadenopathy/organomegaly is more common
  2. Sanctuary site involvement
  3. Can sometimes present like a lymphoma (for example: T-ALL tends to present as a mediastinal mass)
  4. CNS involvement
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20
Q

Origin of ALL (Acute Lymphoblastic Leukemia)

A

hematopoietic stem cell

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21
Q

Genetic abnormalities in ALL-general concepts (3)

A
  1. multiple mutations (not just 1 single mutation can produce ALL)
  2. These varied mutations deregulate transcription factors needed for differentiations aka block normal maturation
  3. Ph chromosome 190 kDA (as opposed to the typical 210kDa we see in CML)
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22
Q

90% ALL cases have numerical or structural chromosomal abnormalities. List the 3

A
  • hyperdiploidy (most common)
  • hypodiploidy
  • balanced translocations
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23
Q

What is the key difference between a meyloblast and a lymphoblast?

A

myeloblast tend to be bigger and have moderate cytoplasm

lymphoblasts are a little smaller, can barely see cytoplasm, and have immature chromatin

when you see a slide collection, you can narrow it doen to ACUTE leukemia, but can’t commit to lymphoid or meyloid. Need to do flow cytometry to determine the lineage

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24
Q

What are prognostic factors for ALL? (3)

Overall, what is the prognosis?

A
  • Age (worse if under 2 or over 10
  • WBC (>100,00/ul), poor prognostic feature
  • Karyotype
    • good: hyerdiploidy, trisomy 4, 7, 10, t(12;21)
    • Philadlephia chromsome t(9;22): good thing about Ph is we have targeted treatment (imatinib/gleevec)

Overall, good prognosis! 78-85% children cured

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25
Q

What is the problem in Non-Hodgkin Lymphomas?

What type of cell (at what stage) does the problem arise?

A
  • Arrest at maturation OR over-proliferation at a particular stage of development
  • arises from mature lymphocytes
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26
Q

Increase in LDH–what is it, what does it mean?

A
  • clinical feature of lymphoma
  • indicates you’re dealing with high grade
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27
Q

“B symptoms”

A

Fever, night sweat, weight loss

associated with lymphomas

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28
Q

Mature B Cell Neoplasms (B-NHL)

Pre germinal center:

A

Mantle cell lymphoma

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29
Q

Mature B Cell Neoplasms (B-NHL)

Germinal center: (3)

A
  • follicular lymphoma
  • burkitt lymphoma
  • DLBCL

*also see hodgkins occur at germinal center, but we’re talking here specifically about non-hodgkins*

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30
Q

Mature B Cell Neoplasms (B-NHL)

Post germinal center: (4)

A
  • CLL
  • Marginal zone lymphomas
  • Waldenstrom macroglobulinemia
  • Multiple Myeloma
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31
Q

Lymphomagenesis: two important general mechanisms

A
  1. activation of proto-oncogenes
  2. inactivation of tumor suppressor genes
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32
Q

What are the two main types of proto-oncogene activations that occur in lymphomas?

A
  • translocation (usually involves immunoglobulin heavy chain gene)
  • point mutation
33
Q

Most common inactivation of tumor suppressor gene in lymphoma development. What is the requirement of this type of inactivation?

A

p53 is most common example

  • you NEED bi-allelic inactivation
  • one allele deleted and one mutated
34
Q

t(14;18)

  • type of lymphoma
  • result of the translocation
A

Follicular lymphoma

Bcl2 over expression (blocks apoptosis)

35
Q

t(11;14)

lymphoma

gene affected

A

Mantle cell lymphoma

BCL1 / Cyclin D1

36
Q

t(8;14)

t(8;2)

t(8;22)

  • lymphoma
  • gene affected
A

Burkitt’s lymphoma

MYC

37
Q

Besides activation of proto-oncogenes, and inactivation of tumor suppressor genes, what are 3 other mechanisms of lymphomagenesis?

A

1. INFECTIONS by oncogenic viruses

  • HHV-8 (primary effusion lymphooma)
  • EBV

2. Antigenic stimulation

  • H. pylori infection
  • MALT lymphoma of the stomach

3. Host immunodeficiency

  • HIV
  • immunosuppressive theraoy
38
Q

Memory B-cells are associated with what two types of lymphomas?

A

1) Chronic Lymphocytic leukemia
2) MALT lymphomas

39
Q

In terms of lymphoma grading, explain the major differences between “low” grade and “high” grade. What are examples of each? (2)

A

Low grade:

indolent, long survival but not curable, disseminated at presentation (follicular lymphoma, CLL/SLL)

High grade:

short survival if untreated, curable (50%) if aggressively treated (DLBCL, Burkitt lymphoma)

40
Q

Ann Arbor Classification / Lymphoma staging

What does “A” “B” and “E” mean?

A

A = no symptoms (think A for Absent)

B = presence of B symptoms

E = Extranodal site contiguous to a nodal site

41
Q

Lymphoma Staging / Ann Arbor Classifications

Briefly describe Stages I-IV

A

I: single lymph node region

II: two lymph node regions on _same side of diaphragm _

III: lymph node regions or structures on both sides of diaphgram

IV: involvement of an extranodal site (beyond E), usually bone marrow or liver

42
Q

two major differences between Non-Hodkin and Hodgkin lymphoma

A

NHL: spreads in less predictable fashion, widespread growth

HL: spreads in predictable fashion, contiguous growth

43
Q

most common leukemia

A

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

44
Q

How do most patients look with CLL/SLL?

What are two possible fates of CLL?

A

many pts are asymptomatic

CLL can transform to more aggresive lymphoid neoplasms:

                 - prolymphocytic transformation (prolymphocytes are large lymphoid cells)
          - Richter's transformation to large B-cell lymphoma
45
Q

4 types of Genetics involved in CLL pathogenesis

A
  • deletions (11q, 13q, 17p)
  • trisomy 12
  • Somatic hypermutated vs Non-mutated Ig variable genes (hypermutated have better prognosis)
  • Notch1 receptor

**unlike most other lymphoid malignancies, translocations are rare in CLL/SLL**

46
Q

Describe CLL morphology on a peripheral blood smear

A

small round lymphocytes with mature chromatin and round nuclei

pattern: clubbed, dark chromatin

47
Q

What exactly is Small lymphocytic lymphoma

A

CLL in a lymph node

basically CLL can present as a leukemia in blood or lymphoma in lymph node, or both.

48
Q

Classic immunophenotype of CLL (3)

A

CD20+ (B-cell)

CD5 (T cell marker, but just so happens to be expressed on CLL, also see in mantle cell lymphoma)

CD23

In addition you’d see: CD45 (general leukocyte marker), CD19, CD20 (B-cell marker), **kappa or lambda light chain restriction **(monoclonality)

49
Q

what does follicular lymphoma typically present with

A

lymphadenopathy

50
Q

Classic immunophenotype of Follicular Lymphoma

A

CD20+

CD10+

BCL2+, BCL6+

(recall that CLL is CD10 negative. CD10 is also see in Burkitt)

also see CD45, CD19

51
Q

follicular pattern

what type of cells do you see

A

nodular pattern

small cell centrocytes

large cell centroblasts

52
Q

does DLBCL have good response to chemo?

A

YES. Good response to intensive combination chemotherapy:

60-80% complete remission

40-50% cured

This goes to show that aggressive (high grade) lymphomas such as DLBCl that may be nodal and/or extranodal can have good response to chemo. In fact, low grade lymphomas are TOUGHER to treat with chemo.

53
Q

DLBCL subtypes (4)

A
  • T-cell/Histiocyte-rich large B-cell lymphoma
  • Primary DLBCl of CNS
  • Primary cutaneous DLBCL, leg type
  • EBV positive DLBCL of the elderly
54
Q

Diffuse Large B-cell Lymphomas are molecularly heterogenous. What are 3 main genes that can be affected?

A

1) BCL6 (translocations with breakpoint in chromosome 3q27; mutations in BCL6 promoter regions
2) BCL2 t(14;18)
3) MYC

55
Q

What is Marginal Zone Lymphoma associated with?

A

Chronic inflammation or infection

56
Q

Lymphoma associated with memory B cells

A

Marginal zone Lymphoma-post germinal center B-cell deviation

57
Q

Marginal Zone lymphoma is comprised of what type of cells? What are the 3 main locations?

A

B-cell lymphocytes comprised of small cells

1) MALT lymphoma (extranodal sites i.e. stomach, thyroid)
2) Nodal marginal zone lymphoma (arising in lymph nodes)
3) splenic marginal zone lymphoma

58
Q

role of persistent antigen stimulation and chronic inflammation

A

polyclonal–> monoclonal

59
Q

Gastric MALT lymphoma:

  • translocations
  • upregulation
  • TF activation
  • effect
A
  • t(11;18), t(14;18), t(1;14)
  • upregulate BCL10 and/or MALT1
  • MALT1/BCL10 complex part of signaling pathway that activates the transcription factor NF-kB
  • NF-kB promotes B-cell proliferation
60
Q

CD10+

A

Follicular Lymphoma, Burkitt Lymphoma

61
Q

Burkitt lymphoma

  • type of cell and marker
  • lymphoma grade, who it occurs in
A
  • high grade, children and young adults
  • MATUREB cells, CD10+
62
Q

Two types of Burkitt lymphoma

A

Endemic:

  • associated with EBV
  • jaw (African)/abdomen(sporadic), visceral mass

Non-endemic:

-ileo-cecal or peritoneal mass

63
Q

What do plasma cell neoplasms secrete?

A

Almost always secrete an antibody or antibody fragment (e.g. light chain)

64
Q

What are the 5 main types of plasma cell neoplasms?

A

1) Plasma cell myeloma (Multiple Myeloma)
2) Waldenstrom Macroglobulinemia
3) Heavy chain disease
4) Amyloidosis (primary)
5) monoclonal gammopathy of undetermined significance (MGUS)

65
Q

What can the M component B in monoclonal plasma cells? (3)

A
  • complete antibody
  • heavy chains
  • light chains (urine: Bence Jones proteins)
66
Q

M-spikes

A

-since neoplastic plasma cells produce immunoglobulin, M spike is seen most commonly due to monoclonal IgG or IgA

present in plasma cell myeloma (Multiple Myeloma) and occasionally found in asymptomatic patients (MGUS)

67
Q

Proliferation and survival of neoplastic plasma cells depends on: (2)

A
  • IL-6
  • bone marrow stromal cells
68
Q

Myeloma cells upregulate pathways. Provide one important example

A

activate osteoclasts–> increased bone resorption –> hypercalcemia

69
Q

Diagnosis of plasma cell myeloma: 3 main signs

A

1) increased # of plasma cells
2) Monoclonal (M spike)
ex. IgG/Kappa, SPEP/UPEP/IFE, increase in serum free light chains
3) end organ damage “CRAB”
- hypercalcemia, renal failure, anemia, lytic bone lesions/back pain

70
Q

Hodkins Lymphoma: 4 clinical and laboratory features

A
  • HL starts in ONE lymph node or chain of nodes, and typically spread to anatomically contiguous lymph nodes
    - lymphadenopathy, splenomegaly, hepatomegaly, bone marrow, other tissues
  • B symptoms (fever, night sweats, weight loss)
  • Anemia, increased ESR (how much inflammation in the body), eosinophilia
  • Cell mediated immune defects
71
Q

Hodgkin Lymphoma pathogenesis

A
  • Hodgkin Reed Sternberg cells (HRS): most often derive from germinal center B cells
    • cells have somatic hypermutation
    • loss of B-cell genes, reprogrammed gene expression
  • Activation of NF-kB
    • multiple signaling pathways and TF are deregulated
    • activation of NF-kB by EBV
    • NF-kB activated: promote lymphocyte survival and prolifreation
    • rescue crippled germinal center B-cells
72
Q

In general, what do HRS cells attract?

A

INFLAMMATORY cells into the tissue (inflammatory cells can make up to 90% of the tumor: HRS are the minority)

73
Q

List the 4 main cytokines/chemokines HRS stimulate and their effects

A
  1. GM-CSF –> increased WBC and monocyte/macrophage activation
  2. IL-5 –> eosinophilia –> TGF-beta –> Fibrosis
  3. TGF-beta –> fibrosis
  4. TNF –> fever, malaise, cachexia, acute/chronic phase proteins
74
Q

Under classical Hodgkin Lymphoma, what are the 4 WHO classifications?

A
  1. nodular sclerosis
  2. lymphocyte rich
  3. lymphocyte depeletion
  4. Mixed cellularity
75
Q

Classical Hodgkin Lymphoma markers (2)

A

CD30+ CD15+

CD20-, CD45-

76
Q

targeted therapy for Hodgkin lymphoma

A

anti-CD30 antibodies

77
Q

early stage HL can be treated with ____

B symptoms require _____

A

early stage (IA, IIA): radiation therapy

B symptoms (and Stage III and IV): chemotherapy

78
Q
A

MOD 3 (19 decks)

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