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Hematologic Malignancies II Flashcards

1
Q

Tingible body macrophages

A

macrophages that have phagocytosed remnants of B-cell nuclei containing hematoxyin

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2
Q

What are the small, dark cells in the germinal center of lymph nodes?

A

centrocytes

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3
Q

What are the larger cells in the germinal center of lymph nodes?

A

centroblasts

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4
Q

In general, a B-cell lymphoma or leukemia derived from well differentiated cells are (more/less) aggressive.

A

less

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5
Q

Acute leukemia is (more/less) aggressive.

A

more

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6
Q

Chronic leukemia is (more/less) aggressive.

A

less

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7
Q

T/F: Malignancies derived from well differentiated cells can transform into more aggressive forms.

A

T

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8
Q

What immunophenotype is associated with B cells in germinal centers and mantle zones?

A

CD20

CD19

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9
Q

What immunophenotype is associated with (some) B cells in germinal centers only?

A

CD10

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10
Q

What immunophenotypes are associated with T cells in the paracortex (mostly)?

A

CD5

CD3

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11
Q

Translocations associated with B cell malignancies:

A

IgH t(8;14) [14q32]

Ig lambda t(8;22) [22q11]

Ig kappa t(8;2) [2p12]

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12
Q

Binding of an oncogene to what other gene causes B cell malignancies?

A

Ig promoter

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13
Q

What oncogene is associated with marginal zone (memory B) malignancies?

A

Pax5

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14
Q

What oncogenes are associated with peri-follicular (plasma cell) malignancies?

A

C-MAF

Cyclin-D3

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15
Q

What oncogenes are associated with interfollicular malignancies?

A

Cyclin-D1

Myc

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16
Q

What oncogenes are associated with follicular malignancies?

A

Bcl-2, Bcl-6

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17
Q

What defines the extent of clinical involvement?

A

staging

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18
Q

What B-cell lymphoproliferative conditions manifest in the peripheral blood, BM and lymph nodes?

A

Chronic lymphocytic Leukemia

Small lymphocytic lymphoma

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19
Q

Where does follicular lymphoma manifest?

A

peripheral blood, BM and lymph nodes

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20
Q

Where does Burkitt’s lymphoma present?

A

GI tract*
Lymph nodes
BM

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21
Q

What disorder is derived from the most mature forms of B cells, mostly inactive memory B?

A

CLL

some in marginal zone

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22
Q

What is the clinical presentation of CLL/SLL?

A

Lymphocytosis in older males

with a high familial incidence

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23
Q

What is the morphology of peripheral blood in CLL/SLL?

A

“smudge”cells

  1. small lymphocytes
  2. little cytoplasm
  3. mature, dense chromatin
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24
Q

What is the morphology of lymph nodes in CLL/SLL?

A
  1. “Pseudofollicular”: slighter larger cells undergoing DNA synth and mitosis
  2. loss of normal architecture
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25
What are the deletions associated with CLL/SLL?
``` del13 del11 del17 (p53 deletion) ``` (*trisomy 12 is another possible cause)
26
What clinical predictors (prognosis) are associated with CLL/SLL?
Markers of somatic hypermutation 1. ZAP-70 expression (bad) 2. CD38 expression (bad) Genetics: 1. 17p deletion (bad) 2. 13q deletion (good) >30% smudge cells (good) increasing fraction of immature prolymphocytes (bad)
27
Immunophenotype associated with: CLL/SLL
CD5, CD23, (weak CD20), light chain restricted *light chain restricted = only kappa or lambda
28
Clinical presentation of mantle cell lymphoma
Lymphadenopathy and/or Lymphocytosis in older males. | might look like CLL
29
What sites are involved in mantle cell lymphoma?
Lymph nodes > bone marrow, spleen, peripheral blood, GI tract
30
What is the morphology of peripheral blood in mantle cell lymphoma? Lymph node morphology?
Peripheral blood: small lymphocytes, little cytoplasm; “smudge”cells Lymph node: Usually homogeneous effacement, ‘starry sky’
31
What is a major difference between mantle cell lymphoma and CLL morphology? Which is more aggressive?
no proliferation centers in the lymph nodes in MCL MCL is more aggressive
32
What are genetic abnormality is associated with mantle cell lymphoma? How is it detected?
t(11;14)(q13;q32) (IgH;Cyclin D1) --cyclin D1 is overexpressed, which pushes the cell from G1 to S phase ALWAYS seen BY FISH
33
Immunotyping associated with mantle cell lymphoma:
Light chain restricted (kappa or lambda) CD5 CD20 (negative for CD23)
34
What is an important clinical predictor of mantle cell lymphoma?
mitotic rate, detected by Ki-67 immunostain
35
Plasma cell neoplasms are common is what age group?
elderly
36
How does a mild form of plasma cell neoplasm present? Severe form?
Mild: 1. asymptomatic 2. monoclonal gammopathy of uncertain significance (MGUS) 3. increased total protein on labs with Rouleaux on periph smear Severe: lytic bone lesions, pain, fractures, renal failure (lytic bone lesions = plasma cell myeloma)
37
What effect do increased plasma cells have on bone?
erode bone, leaving radiologically evident bone lesions
38
Immunophenotype of plasma cell neoplams:
CD38 CD138 light chain restricted (CD19 and CD20 are negative)
39
T/F: If/when MGUS progresses to multiple myeloma, patients survive ~3-4 years.
T
40
What genetic abnormalities are associated with plasma cell neoplasms?
Translocation of IgH to various oncogenes (dx with FISH) | Trisomies of odd numbered chromosomes
41
What are negative clinical predictors associated with plasma cell neoplasms?
``` Serum beta 2 microglobulin t(4;14) FGFR3 t(14;16) C-MAF t(14;20) MAFB del 17p (p53) ```
42
Overexpression of what protein is associated with failure of germinal center B cells to apoptose?
Bcl-2
43
What lymph node morphology is associated with follicular lymphoma?
1. Enlarged lymph node with many follicles 2. no cell polarity 3. no tingible-body macrophages (no apoptosis of B cells) 4. fewer mitotic figures
44
How does follicular lymphoma present?
- Lymphadenopathy in older individuals - Can be otherwise asymptomatic - may involve BM or peripheral blood - 30% eventually become diffuse large Bcell lymphoma
45
Most common genetic abnormality associated with follicular lymphoma:
t(14;18) | *Bcl-2/IgH
46
Immunophenotype associated with follicular lymphoma
``` CD19+ CD20+ CD10+ BCL-2 (90%) BCL-6 (85%) ```
47
How is follicular lymphoma graded?
by how many large cells (centroblasts) are present (**this predicts prognosis) Grade 1: mostly centrocytes Grade 3: mostly centroblasts
48
Immunophenotype of diffuse large B-cell lymphoma:
CD19+, CD20+, CD10+
49
How does diffuse large B-cell lymphoma present?
1. Rapidly growing adenopathy 2. elderly 3. extranodal disease (GI tract, bone marrow, etc) in 40%
50
What genetic abnormalities are often associated with diffuse large B-cell lymphoma?
t(14;18) | t(v, 3q27)(v, BCL-6)
51
Hodgkin lymphoma's clinical presentation:
- Males, age 30-50 - Localized or diffuse adenopathy - Often involvement of cervical, mediastinal, or abdominal lymph nodes, and/or spleen
52
What morphology is associated with classical Hodgkin lymphoma?
1. Reed/Sternberg cells (large mono- or binucleate cells with eosinophilic nuclei; likely horseshoe shaped) 2. Diverse background cells 3. May have collagenous bands
53
What morphology is associated with Nodular Lymphocyte Predominant Hodgkin lymphoma?
1. Popcorn cells (lympho-histocytic L&H cells) instead of classic RS cells 2. Mostly lymphocytes in background
54
What are 4 features of Reed-Sternberg cells?
1. contain clonal, rearranged Ig V genes 2. can't be killed (due to constitutive NFkB expression, EBV, mutations in anti-apoptotic pathways) 3. genetic instability (likely to keep mutating) 4. no Ig expressin in/on cell *these cells should die in germinal centers, but don't
55
4 Morphology patterns associated with classical Hodgkin lymphoma:
1. Nodular sclerosis pattern (bands) 2. Mixed cellularity pattern (no bands) 3. Lymphocyte rich pattern (lymphocyte rich) 4. Lymphocyte depleted pattern (large # R-S cells)
56
Immunophenotype of classical Hodgkin lymphoma (R/S cells):
CD30 CD15 Pax5 (Bcell transcription factor) (CD20 negative) *these cells are too fragile for flow cytometry
57
T/F: Classical Hodgkin lymphoma usually has a very poor prognosis, even with treatment
F: curable with chemo and radiation | 97% 10 yr survival
58
How are R-S cells in NLP and classical Hodgkin different?
NLP expresses Ig and other markers; they do NOT have the Ig promoter and transcription factor mutations NLP has (like classical) 1. genetic instability 2. cant be killed (mutations, EBV, NFkB)
59
Immunophenotype of NLP Hodgkin lymphoma (L&H cells):
CD20+ PAX5 (CD30 and CD15 negative) *L&H cells too fragile for flow cytometry
60
What is significant about the relationship between T cells and R/S cells in NLP Hodgkin?
T cells surround R/S cells
61
What may NLP Hodgkin progress to?
diffuse large B-cell lymphoma

Heme (38 decks)

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