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Oncology > 6 - B Cell Lymphomas > Flashcards

6 - B Cell Lymphomas Flashcards

1
Q

What is lymphoma?

A

Clonal disease of blood cells and lymph nodes

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2
Q

Lymphocyte origin story

A

Originate in the bone marrow

Travel peripherally through blood and lymphatic system to lymph nodes

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3
Q

Leukemia defined by

A

Presence of malignant lymphocytes in circulation

This can overlap with lymphoma

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4
Q

Lymphoma defined by

A

Proliferation arising in a discrete tissue

This can overlap with leukemia

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5
Q

B-Cell Non-Hodgkins Lymphomas - Range of Clinical Presentations

A

Indolent → Aggressive

Expansion of lymphocytes:
Enlargement of lymph nodes, spleen - 
Invasion into extranodal sites
Superior Vena Cava Syndrome (compressing SVC)
CSF inovlement
Cytopenias - 
Infections
Anemia (fatigue)
Thrombocytopenia (Bleeding, petechiae)
Cytokine secretion:
B symptoms - 
Fever
Weight loss
Pruritus

Paraneoplastic Syndromes:
Nephrotic Syndrome
Hemolytic Anemia & ITP

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6
Q

B-Cell Non-Hodgkins Lymphomas - Approach to History

A

Duration of symptoms

Environmental factors:
Chronic infections
Autoimmune diseases
Chemicals and radiation

Ethnicity and place of birth
Family history and # of siblings (to think about allogeneic transplant ahead of time)

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7
Q

B-Cell Non-Hodgkins Lymphomas - Approach to Exam

A

Lymphadenopathy
Hepatosplenomegaly
Rash

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8
Q

B-Cell Non-Hodgkins Lymphomas - Approach to Imaging

A

PET/CT Scan
Avidity of nodes on PET
Distribution and size of nodes

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9
Q

B-Cell Non-Hodgkins Lymphomas - Approach to Labs

A 
LDH
CBC
SPEP
ESR
Beta-2 Microglobulin
Lumbar puncture
HIV, HBV, HCV, EBV, CMV, HTLV-1
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10
Q

B-Cell Non-Hodgkins Lymphomas - Diagnosis

A

Excisional or Core biopsy of the HOTTEST node on the PET scan:

Histologic exam
Immunohistochemistry phenotype
Cytogenetics
FISH (Fluorescence in situ Hybridization)
PCR
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11
Q

B-Cell Non-Hodgkins Lymphomas - Stage I

A

1 Lymph node chain on one side of the diaphragm

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12
Q

B-Cell Non-Hodgkins Lymphomas - Stage II

A

2 Lymph node chains on one side of the diaphragm

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13
Q

B-Cell Non-Hodgkins Lymphomas - Stage III

A

Lymph node chains on both sides of the diaphragm

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14
Q

B-Cell Non-Hodgkins Lymphomas - Stae IV

A

Extranodal disease or bone marrow involvement

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15
Q

B-Cell Non-Hodgkins Lymphomas - Factors in IPI scores

A

International Prognostic Index is the actual way to tell prognosis.

1 Point each for:
Age > 60
[Serum LDH] above normal
ECOG performance status ≥ 2
Stage III or IV
# of extranodal disease sites > 1
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16
Q

ECOG Performance Status - 0

A

Fully active without restriction

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17
Q

ECOG Performance Status - 1

A

Activity restricted
Ambulatory
“Light” walk only

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18
Q

ECOG Performance Status - 2

A

Ambulatory
All self-care
No work activities
sp>50% waking hours

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19
Q

ECOG Performance Status - 3

A

Limited self-care

Confined >50% waking hours

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20
Q

ECOG Performance Status - 4

A

Completely disabled

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21
Q

B-Cell Non-Hodgkins Lymphomas - IPI Score - 0 to 1

A

Low Risk

91% 3-year survival

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22
Q

B-Cell Non-Hodgkins Lymphomas - IPI Score - 2

A

Low - Intermediate Risk

81% 3-year survival

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23
Q

B-Cell Non-Hodgkins Lymphomas - IPI Score - 3

A

High - Intermediate Risk

65% 3-year survival

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24
Q

B-Cell Non-Hodgkins Lymphomas - IPI Score - 4 to 5

A

High Risk

59% 3-year survival

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25
Q

Follicular Lymphoma - Genetic Abnormality

A

t(14;18)

BCL2

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26
Q

Mantle Cell Lymphoma - Genetic Abnormality

A

t(11;14)

Cyclin D1

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27
Q

Burkitt Lymphoma - Genetic Abnormality

A

t(8;14), t(8;22)
t(2;8)
C-MYC

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28
Q

Diffuse Large B-Cell Lymphoma - Incidence

A

~25,000/year
Most common lymphoma
Can arise anywhere on the body

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29
Q

Diffuse Large B-Cell Lymphoma - Morphology

A

Large cell size (4 - 5x the size of a normal lymphocyte)

Diffuse growth pattern

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30
Q

Diffuse Large B-Cell Lymphoma - Immunohistochemistry

A

(+)CD19, CD20

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31
Q

Diffuse Large B-Cell Lymphoma - CD10+

A

Germinal Center Subtype

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32
Q

Diffuse Large B-Cell Lymphoma - CD10-, Bcl6-

A

Non-Germinal Center (ABC) subtype

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33
Q

Diffuse Large B-Cell Lymphoma - CD10-, Bcl6+, MUM1+

A

Non-Germinal Center (ABC) Subtype

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34
Q

Diffuse Large B-Cell Lymphoma - CD10-, Bcl6+, MUM1-

A

Germinal Center Subtype

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35
Q

Diffuse Large B-Cell Lymphoma - 3 Subtypes

A

Germinal Center B-Cell-like
Activated B-Cell-like
Type 3

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36
Q

Diffuse Large B-Cell Lymphoma - Germinal Center type (GC)

A

Mutations of BCL6, HATs & EZH2

Lead to repressed transcriptional state

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37
Q

Diffuse Large B-Cell Lymphoma - Activated B-Cell (ABC) type

A

Mutations of B-Cell Receptor Pathway

Lead to unchecked activation of NFkB

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38
Q

Germinal Center-Derived - When a B Cell enters the dark zone of the follicle - Normal

A

EZH2 & Bcl6 are upregulated, allowing for growth and evasion of apoptosis until they receive signals to downregulate as the cell enters the light zone.

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39
Q

Germinal Center-Derived Diffuse Large B-Cell Lymphoma

A

Mutations in EZH2, Bcl6 & Bcl2 to prevent their downregulation.

This decreases MLL & HAT

This drives lymphoma production

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40
Q

Activated B-Cell Diffuse Large B-Cell Lymphoma

A 
Decreased suppression of NFkB
Tonic signaling of BCR pathways
Mutations:
MYD88
CARD11
A20
CD79b
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41
Q

Activated B-Cell Diffuse Large B-Cell Lymphoma - Ibrutinib

A

Inhibits BTK pathway

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42
Q

Activated B-Cell Diffuse Large B-Cell Lymphoma - Lenalidomide

A

Inhibits NFkB pathway

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43
Q

Diffuse Large B-Cell Lymphoma - Treatment

A

R-CHOP

Rituximab (375 mg/m2)
Cyclophosphamide (750 mg/m2)
Doxorubicin (50 mg/m2)
Vincristine (1.4 mg/m2)
Prednisone (100 mg PO days 1 - 5)

Growth Factor Support
Antibiotic prophylaxis in the elderly

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44
Q

Cyclophosphamide - Side Effect

A

Hemorrhagic Cystitis

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45
Q

Cyclophosphamide - Mechanism of action

A

Aklylating agent

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46
Q

Doxorubicin - Mechanism of action

A

Topoisomerase II Inhibitor

47
Q

Doxorubicin - Side effect

A

Cardiomyopathy

48
Q

Vincristine - Mechanism of action

A

Antimicrotubular

49
Q

Vincristine - Side effect

A

Neuropathy

50
Q

Rituximab

A

Monoclonal antibody to CD20
Opsonizes B cells for attack and killing (3 pathways)
Human-Mouse chimera (so can have allergic reactions)

51
Q

3 mechanisms of B-Cell killing induced by Rituximab

A

Complement-mediated cytotoxicity
ADCC (phagocytosis via macrophages)
Direct lysis from NK cells

52
Q

Pre-treatment for Rituximab to take into account the mouse particles

A

Acetaminophen
Diphenhydramine

Have Hydrocortisone on hand just in case

Also useful are Dexamethasone and Famotidine

53
Q

Risks with Rituximab

A

Allergy
Tumor lysis when malignant lymphocytes > 25,000
Progressive Multifocal Leukoencephalopathy (JC Virus)
Reactivation of HBV
Hypogammaglobulinemia

54
Q

Diffuse Large B-Cell Lymphoma - Immunodeficiency-Associated

A

In the setting of T-Cell immunodeficiency:
Advanced HIV
Post Allo-transplant
Usually associated with EBV

55
Q

Diffuse Large B-Cell Lymphoma - Primary Effusion Lymphoma

A

KSHV/HHV-8 Associated

HIV-Associated or elderly

56
Q

Double Hit Lymphoma

A 
Diffuse Large B-Cell Lymphoma harboring 2 translocations involving MYC and BCL2 or BCL6
Represent 6 - 14% of DLBCL
13% end up with CNS disease
Disease of the elderly
Average age approaches 71
57
Q

Double Protein Lymphoma

A

Equally poor prognosis to Double Hit

Immuno HistoChemistry remains undefined method for evaluating for Double Hit Lymphoma

58
Q

DLBCL-U

A

Diffuse Large B-Cell Lymphoma - Unclassifiable

59
Q

Etoposide

A

Added to infusional chemotherapy for:

DLBCL-U/Double Hit/Double Protein Lymphoma
HIV-Associated Lymphoma
PTLD
PMBCL

It helps!

60
Q

PTLDLBCL

A

Post-Transplant Diffuse Large B Cell Lymphoma

Almost always driven by EBV

61
Q

PTLDLBCL - Early lesions

A

Reflect EBV infections

62
Q

PTLDLBCL - Polymorphic

A

Effacement of the lymphoid architecture
Doesn’t quite meet criteria for clonal or monomorphic state
Majority are associated with EBV

63
Q

PTLDLBCL - Monomorphic

A 
DLBCL
Burkitt's
PTCL
Plasma Cell Disorders
50% associated with EBV
64
Q

PTLDLBCL - Hodgkin or Hodgkin-like

65
Q

PMDLBCL

A

Type 3
Primary Mediastinal Large B-Cell Lymphoma
Cell of origin (COO) closer to HL than DLBCL
CD30+
CD20+
nuckeal c-rel
TRAF-1
Female young adults
Large mediastinal mass (Leading to SVC Syndrome, Thrombosis)

66
Q

PMDLBCL - Treatment

A

Less emphasis on radiation, and on-going study of predictive value of PET while treating with Etoposide

67
Q

Burkitt Lymphoma - Common Features

A

Rapid enlargement of lymphadenopathy (within days)
All subtypes driven by C-MYC translocation
Often associated with EBV infection
All have Starry Sky appearance
All Aggressive but respond to combination chemotherapy

68
Q

Burkitt Lymphoma - Combination Chemotherapy

A

Codox-M-IVAC

Very effective

69
Q

Burkitt Lymphoma - 3 Variants

A

HIV Associated
African Endemic
Sporadic

70
Q

Burkitt Lymphoma - HIV Associated

A

25% latent EBV infection

71
Q

Burkitt Lymphoma - African Endemic

A

All EBV infected
Mostly in children

Mass involving:
Mandible
Abdominal viscera
Kidneys
Ovaries
Adrenals
72
Q

Burkitt Lymphoma - Sporadic

A

15 - 20% EBV infected
IgH locus translocations t(8;14)
Most common lymphoma in children
Ileocecum and peritoneum

73
Q

Burkitt Lymphoma - Morphology

A

Effaced by diffuse infiltrate
Intermediate size round or oval nuclei
High mitotic index and numerous apoptotic cells
Nuclear remnants are phagocytosed by benign macrophages

74
Q

Burkitt Lymphoma - Immunophenotype

A 
IgM
CD19+
CD20+
CD10+
BCL6+

Almost NEVER expresses BCL2

75
Q

Burkitt Lymphoma - Molecular

A

Translocation C-MYC gene
t(8;14) - IgH
t(8;22) - Lambda
t(2;8) - IgKappa

p53 mutations

76
Q

Follicular Lymphoma

A

Second most common lymphoma out there
Very indolent & slow growing
Translocation t(14;18)
Upregulation of BCL2

77
Q

Follicular Lymphoma - Clinical Picture

A

Painless, generalized lymphadenopathy
Indolent waxing and waning course
Bone marrow involvement in 85%
Histologic transformation in 30 - 50%

Incurable - Median survival 7 - 9 years

78
Q

Follicular Lymphoma - Treatment

A 
Watch and wait
Rituximab-based therapy
CHOP or CVP
Bendamustine
XRT for stage I disease
79
Q

Bendamustine - Mechanism of action

A

Purine analogue / Alkylating agent hybrid

80
Q

Bendamustine - Side effect

A

Cytopenias

81
Q

Follicular Lymphoma - Morphology

A

Nodular pattern
Small cells with irregular or cleaved nuclear contours
Grade depends on # of large cells
Grades: 1 - 2, 3a, 3b

82
Q

Follicular Lymphoma - Grade 3B

A

Treated like DLBCL

83
Q

Follicular Lymphoma - Immunophenotype

A 
BCL2+
CD19+
CD20+
CD10+
BCL6+
CD5-
84
Q

Mantle Cell Lymphoma - 4 Variants

A

Blastic
Aggressive
Indolent
Leukemic

85
Q

Ki67

A

Proliferative Index

86
Q

Mantle Cell Lymphoma - Blastic

A

Ki67 > 90% (90% of cells are proliferating at any time)

87
Q

Mantle Cell Lymphoma - Aggressive

A

Ki67 > 25% (25% of cells are proliferating at any time)

88
Q

Mantle Cell Lymphoma - Indolent

A

Ki67 ~ 10% (10% of cells are proliferating at any time)

89
Q

Mantle Cell Lymphoma - Leukemic

A

Indolent, behaves like CLL

90
Q

Mantle Cell Lymphoma - Treatment

A

Guided by variant

Blastic & Aggressive:
Aggressive chemotherapy & transplant
R-Hyper CVAD followed by autologous stem cell transplant
High dose cytarabine

Indolent & Leukemic:
Bendamustine
Bortezomib

Relapse:
Ibrunitiv & Idelalisib

The most indolent ones (behaving like Follicular Lymphoma) we can watch and wait

91
Q

Bortezomib - Mechanism of action

A

Proteosome inhibitor

92
Q

Bortezomib - Side effect

A

Neuropathy

93
Q

Mantle Cell Lymphoma - Morphology

A

Nodular to diffuse

Small lymphocytes

94
Q

Mantle Cell Lymphoma - Immunohistochemistry

A 
Cyclin D1+
CD19+
CD20+
CD5+
CD23-
95
Q

Mantle Cell Lymphoma - Molecular

96
Q

Extra-Nodal Marginal Zone Lymphoma (MALT)

A

Driven by antigenic stimulation

Treat the underlying antigenic stimulus, and lymphoma goes away

97
Q

Salivary Gland MALT caused by

A

Sjogren Disease

98
Q

Thyroid MALT caused by

A

Hashimoto’s Thyroiditis

99
Q

Gastric MALT caused by

100
Q

Splenic MALT caused by

101
Q

Bronchial MALT caused by

A

Chlamydia Psittaci

102
Q

Ocular Adnexa MALT caused by

A

Chlamydia Psittaci

103
Q

Skin MALT caused by

A

Borrelia Burgdorferi/Afzelii

104
Q

Intestinal MALT caused by

A

Campylobacter Jejuni

105
Q

Lymphoplasmacytic Lymphoma (Waldenstrom’s Macroglobulinemia)

A 
Indolent
Secrete IgM:
Hyperviscosity
Visual Impairment
Neurologic problems
Bleeding
Cryoglobulinemia
106
Q

Lymphoplasmacytic Lymphoma - Morphology

A

Plasmacytoid
PAS staining Ig inclusions (Russell & Dutcher bodies)
Serup Plasma Electrophoresis - See a spike in monoclonal IgM

107
Q

Follicular Lymphoma - Surface Markers

A

CD10+

CD23+/-

108
Q

Mantle Zone Lymphoma - Surface Markers

A

CD5+

Cyclin D1+

109
Q

Marginal Zone Lymphoma - Surface Markers

110
Q

CLL/SLL - Surface Markers

A

CD5+

CD23+

111
Q

Lymphoplasmacytic Lymphoma - Surface Markers

112
Q

Ibrutinib

A

First in class Bruton’s tyrosine kinase (BTK) inhibitor
Highly effective in lymphomas with tonic BCR signaling
Approved for relapsed Mantle Cell Lymphoma and CLL

113
Q

Idelalisib

A

PI3Kδ Inhibitor

Approved in patients with Relapsed Indolent Lymphoma & CLL

114
Q

Prognosis of DLBCL

A

Predicted by cell of origin

Oncology (23 decks)

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