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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
Q

What are the deletions associated with CLL/SLL?

A 
del13
del11
del17 (p53 deletion)

(*trisomy 12 is another possible cause)

26
Q

What clinical predictors (prognosis) are associated with CLL/SLL?

A

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
Q

Immunophenotype associated with: CLL/SLL

A

CD5, CD23, (weak CD20), light chain restricted

*light chain restricted = only kappa or lambda

28
Q

Clinical presentation of mantle cell lymphoma

A

Lymphadenopathy and/or Lymphocytosis in older males.

might look like CLL

29
Q

What sites are involved in mantle cell lymphoma?

A

Lymph nodes > bone marrow, spleen, peripheral blood, GI tract

30
Q

What is the morphology of peripheral blood in mantle cell lymphoma? Lymph node morphology?

A

Peripheral blood: small lymphocytes, little cytoplasm; “smudge”cells

Lymph node: Usually homogeneous effacement, ‘starry sky’

31
Q

What is a major difference between mantle cell lymphoma and CLL morphology? Which is more aggressive?

A

no proliferation centers in the lymph nodes in MCL

MCL is more aggressive

32
Q

What are genetic abnormality is associated with mantle cell lymphoma? How is it detected?

A

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
Q

Immunotyping associated with mantle cell lymphoma:

A

Light chain restricted (kappa or lambda)
CD5
CD20
(negative for CD23)

34
Q

What is an important clinical predictor of mantle cell lymphoma?

A

mitotic rate, detected by Ki-67 immunostain

35
Q

Plasma cell neoplasms are common is what age group?

36
Q

How does a mild form of plasma cell neoplasm present? Severe form?

A

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
Q

What effect do increased plasma cells have on bone?

A

erode bone, leaving radiologically evident bone lesions

38
Q

Immunophenotype of plasma cell neoplams:

A

CD38
CD138
light chain restricted
(CD19 and CD20 are negative)

39
Q

T/F: If/when MGUS progresses to multiple myeloma, patients survive ~3-4 years.

40
Q

What genetic abnormalities are associated with plasma cell neoplasms?

A

Translocation of IgH to various oncogenes (dx with FISH)

Trisomies of odd numbered chromosomes

41
Q

What are negative clinical predictors associated with plasma cell neoplasms?

A 
Serum beta 2 microglobulin
t(4;14)   FGFR3   
t(14;16)  C-MAF
t(14;20)  MAFB
del 17p (p53)
42
Q

Overexpression of what protein is associated with failure of germinal center B cells to apoptose?

43
Q

What lymph node morphology is associated with follicular lymphoma?

A
  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
Q

How does follicular lymphoma present?

A
  • Lymphadenopathy in older individuals
  • Can be otherwise asymptomatic
  • may involve BM or peripheral blood
  • 30% eventually become diffuse large Bcell lymphoma
45
Q

Most common genetic abnormality associated with follicular lymphoma:

A

t(14;18)

*Bcl-2/IgH

46
Q

Immunophenotype associated with follicular lymphoma

A 
CD19+
CD20+
CD10+ 
BCL-2   (90%)
BCL-6   (85%)
47
Q

How is follicular lymphoma graded?

A

by how many large cells (centroblasts) are present (**this predicts prognosis)
Grade 1: mostly centrocytes
Grade 3: mostly centroblasts

48
Q

Immunophenotype of diffuse large B-cell lymphoma:

A

CD19+, CD20+, CD10+

49
Q

How does diffuse large B-cell lymphoma present?

A
  1. Rapidly growing adenopathy
  2. elderly
  3. extranodal disease (GI tract, bone marrow, etc) in 40%
50
Q

What genetic abnormalities are often associated with diffuse large B-cell lymphoma?

A

t(14;18)

t(v, 3q27)(v, BCL-6)

51
Q

Hodgkin lymphoma’s clinical presentation:

A
  • Males, age 30-50
  • Localized or diffuse adenopathy
  • Often involvement of cervical, mediastinal, or abdominal lymph nodes, and/or spleen
52
Q

What morphology is associated with classical Hodgkin lymphoma?

A
  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
Q

What morphology is associated with Nodular Lymphocyte Predominant Hodgkin lymphoma?

A
  1. Popcorn cells (lympho-histocytic L&H cells) instead of classic RS cells
  2. Mostly lymphocytes in background
54
Q

What are 4 features of Reed-Sternberg cells?

A
  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
Q

4 Morphology patterns associated with classical Hodgkin lymphoma:

A
  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
Q

Immunophenotype of classical Hodgkin lymphoma (R/S cells):

A

CD30
CD15
Pax5 (Bcell transcription factor)
(CD20 negative)

*these cells are too fragile for flow cytometry

57
Q

T/F: Classical Hodgkin lymphoma usually has a very poor prognosis, even with treatment

A

F: curable with chemo and radiation

97% 10 yr survival

58
Q

How are R-S cells in NLP and classical Hodgkin different?

A

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
Q

Immunophenotype of NLP Hodgkin lymphoma (L&H cells):

A

CD20+
PAX5
(CD30 and CD15 negative)

*L&H cells too fragile for flow cytometry

60
Q

What is significant about the relationship between T cells and R/S cells in NLP Hodgkin?

A

T cells surround R/S cells

61
Q

What may NLP Hodgkin progress to?

A

diffuse large B-cell lymphoma

Heme (38 decks)

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