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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
Follicular Lymphoma - Genetic Abnormality
t(14;18) | BCL2
26
Mantle Cell Lymphoma - Genetic Abnormality
t(11;14) | Cyclin D1
27
Burkitt Lymphoma - Genetic Abnormality
t(8;14), t(8;22) t(2;8) C-MYC
28
Diffuse Large B-Cell Lymphoma - Incidence
~25,000/year Most common lymphoma Can arise anywhere on the body
29
Diffuse Large B-Cell Lymphoma - Morphology
Large cell size (4 - 5x the size of a normal lymphocyte) | Diffuse growth pattern
30
Diffuse Large B-Cell Lymphoma - Immunohistochemistry
(+)CD19, CD20
31
Diffuse Large B-Cell Lymphoma - CD10+
Germinal Center Subtype
32
Diffuse Large B-Cell Lymphoma - CD10-, Bcl6-
Non-Germinal Center (ABC) subtype
33
Diffuse Large B-Cell Lymphoma - CD10-, Bcl6+, MUM1+
Non-Germinal Center (ABC) Subtype
34
Diffuse Large B-Cell Lymphoma - CD10-, Bcl6+, MUM1-
Germinal Center Subtype
35
Diffuse Large B-Cell Lymphoma - 3 Subtypes
Germinal Center B-Cell-like Activated B-Cell-like Type 3
36
Diffuse Large B-Cell Lymphoma - Germinal Center type (GC)
Mutations of BCL6, HATs & EZH2 | Lead to repressed transcriptional state
37
Diffuse Large B-Cell Lymphoma - Activated B-Cell (ABC) type
Mutations of B-Cell Receptor Pathway | Lead to unchecked activation of NFkB
38
Germinal Center-Derived - When a B Cell enters the dark zone of the follicle - Normal
EZH2 & Bcl6 are upregulated, allowing for growth and evasion of apoptosis until they receive signals to downregulate as the cell enters the light zone.
39
Germinal Center-Derived Diffuse Large B-Cell Lymphoma
Mutations in EZH2, Bcl6 & Bcl2 to prevent their downregulation. This decreases MLL & HAT This drives lymphoma production
40
Activated B-Cell Diffuse Large B-Cell Lymphoma
``` Decreased suppression of NFkB Tonic signaling of BCR pathways Mutations: MYD88 CARD11 A20 CD79b ```
41
Activated B-Cell Diffuse Large B-Cell Lymphoma - Ibrutinib
Inhibits BTK pathway
42
Activated B-Cell Diffuse Large B-Cell Lymphoma - Lenalidomide
Inhibits NFkB pathway
43
Diffuse Large B-Cell Lymphoma - Treatment
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
44
Cyclophosphamide - Side Effect
Hemorrhagic Cystitis
45
Cyclophosphamide - Mechanism of action
Aklylating agent
46
Doxorubicin - Mechanism of action
Topoisomerase II Inhibitor
47
Doxorubicin - Side effect
Cardiomyopathy
48
Vincristine - Mechanism of action
Antimicrotubular
49
Vincristine - Side effect
Neuropathy
50
Rituximab
Monoclonal antibody to CD20 Opsonizes B cells for attack and killing (3 pathways) Human-Mouse chimera (so can have allergic reactions)
51
3 mechanisms of B-Cell killing induced by Rituximab
Complement-mediated cytotoxicity ADCC (phagocytosis via macrophages) Direct lysis from NK cells
52
Pre-treatment for Rituximab to take into account the mouse particles
Acetaminophen Diphenhydramine Have Hydrocortisone on hand just in case Also useful are Dexamethasone and Famotidine
53
Risks with Rituximab
Allergy Tumor lysis when malignant lymphocytes > 25,000 Progressive Multifocal Leukoencephalopathy (JC Virus) Reactivation of HBV Hypogammaglobulinemia
54
Diffuse Large B-Cell Lymphoma - Immunodeficiency-Associated
In the setting of T-Cell immunodeficiency: Advanced HIV Post Allo-transplant Usually associated with EBV
55
Diffuse Large B-Cell Lymphoma - Primary Effusion Lymphoma
KSHV/HHV-8 Associated | HIV-Associated or elderly
56
Double Hit Lymphoma
``` 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
Double Protein Lymphoma
Equally poor prognosis to Double Hit | Immuno HistoChemistry remains undefined method for evaluating for Double Hit Lymphoma
58
DLBCL-U
Diffuse Large B-Cell Lymphoma - Unclassifiable
59
Etoposide
Added to infusional chemotherapy for: DLBCL-U/Double Hit/Double Protein Lymphoma HIV-Associated Lymphoma PTLD PMBCL It helps!
60
PTLDLBCL
Post-Transplant Diffuse Large B Cell Lymphoma | Almost always driven by EBV
61
PTLDLBCL - Early lesions
Reflect EBV infections
62
PTLDLBCL - Polymorphic
Effacement of the lymphoid architecture Doesn't quite meet criteria for clonal or monomorphic state Majority are associated with EBV
63
PTLDLBCL - Monomorphic
``` DLBCL Burkitt's PTCL Plasma Cell Disorders 50% associated with EBV ```
64
PTLDLBCL - Hodgkin or Hodgkin-like
Rare
65
PMDLBCL
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
PMDLBCL - Treatment
Less emphasis on radiation, and on-going study of predictive value of PET while treating with Etoposide
67
Burkitt Lymphoma - Common Features
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
Burkitt Lymphoma - Combination Chemotherapy
Codox-M-IVAC | Very effective
69
Burkitt Lymphoma - 3 Variants
HIV Associated African Endemic Sporadic
70
Burkitt Lymphoma - HIV Associated
25% latent EBV infection
71
Burkitt Lymphoma - African Endemic
All EBV infected Mostly in children ``` Mass involving: Mandible Abdominal viscera Kidneys Ovaries Adrenals ```
72
Burkitt Lymphoma - Sporadic
15 - 20% EBV infected IgH locus translocations t(8;14) Most common lymphoma in children Ileocecum and peritoneum
73
Burkitt Lymphoma - Morphology
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
Burkitt Lymphoma - Immunophenotype
``` IgM CD19+ CD20+ CD10+ BCL6+ ``` Almost NEVER expresses BCL2
75
Burkitt Lymphoma - Molecular
Translocation C-MYC gene t(8;14) - IgH t(8;22) - Lambda t(2;8) - IgKappa p53 mutations
76
Follicular Lymphoma
Second most common lymphoma out there Very indolent & slow growing Translocation t(14;18) Upregulation of BCL2
77
Follicular Lymphoma - Clinical Picture
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
Follicular Lymphoma - Treatment
``` Watch and wait Rituximab-based therapy CHOP or CVP Bendamustine XRT for stage I disease ```
79
Bendamustine - Mechanism of action
Purine analogue / Alkylating agent hybrid
80
Bendamustine - Side effect
Cytopenias
81
Follicular Lymphoma - Morphology
Nodular pattern Small cells with irregular or cleaved nuclear contours Grade depends on # of large cells Grades: 1 - 2, 3a, 3b
82
Follicular Lymphoma - Grade 3B
Treated like DLBCL
83
Follicular Lymphoma - Immunophenotype
``` BCL2+ CD19+ CD20+ CD10+ BCL6+ CD5- ```
84
Mantle Cell Lymphoma - 4 Variants
Blastic Aggressive Indolent Leukemic
85
Ki67
Proliferative Index
86
Mantle Cell Lymphoma - Blastic
Ki67 > 90% (90% of cells are proliferating at any time)
87
Mantle Cell Lymphoma - Aggressive
Ki67 > 25% (25% of cells are proliferating at any time)
88
Mantle Cell Lymphoma - Indolent
Ki67 ~ 10% (10% of cells are proliferating at any time)
89
Mantle Cell Lymphoma - Leukemic
Indolent, behaves like CLL
90
Mantle Cell Lymphoma - Treatment
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
Bortezomib - Mechanism of action
Proteosome inhibitor
92
Bortezomib - Side effect
Neuropathy
93
Mantle Cell Lymphoma - Morphology
Nodular to diffuse | Small lymphocytes
94
Mantle Cell Lymphoma - Immunohistochemistry
``` Cyclin D1+ CD19+ CD20+ CD5+ CD23- ```
95
Mantle Cell Lymphoma - Molecular
t(11;14)
96
Extra-Nodal Marginal Zone Lymphoma (MALT)
Driven by antigenic stimulation | Treat the underlying antigenic stimulus, and lymphoma goes away
97
Salivary Gland MALT caused by
Sjogren Disease
98
Thyroid MALT caused by
Hashimoto's Thyroiditis
99
Gastric MALT caused by
H. Pylori
100
Splenic MALT caused by
HCV
101
Bronchial MALT caused by
Chlamydia Psittaci
102
Ocular Adnexa MALT caused by
Chlamydia Psittaci
103
Skin MALT caused by
Borrelia Burgdorferi/Afzelii
104
Intestinal MALT caused by
Campylobacter Jejuni
105
Lymphoplasmacytic Lymphoma (Waldenstrom's Macroglobulinemia)
``` Indolent Secrete IgM: Hyperviscosity Visual Impairment Neurologic problems Bleeding Cryoglobulinemia ```
106
Lymphoplasmacytic Lymphoma - Morphology
Plasmacytoid PAS staining Ig inclusions (Russell & Dutcher bodies) Serup Plasma Electrophoresis - See a spike in monoclonal IgM
107
Follicular Lymphoma - Surface Markers
CD10+ | CD23+/-
108
Mantle Zone Lymphoma - Surface Markers
CD5+ | Cyclin D1+
109
Marginal Zone Lymphoma - Surface Markers
NONE
110
CLL/SLL - Surface Markers
CD5+ | CD23+
111
Lymphoplasmacytic Lymphoma - Surface Markers
IgM+
112
Ibrutinib
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
Idelalisib
PI3Kδ Inhibitor | Approved in patients with Relapsed Indolent Lymphoma & CLL
114
Prognosis of DLBCL
Predicted by cell of origin

Oncology (23 decks)

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