Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Heme Week 2 > Hematologic Malignancies V: B-cell lymphomas/leukemias > Flashcards

Hematologic Malignancies V: B-cell lymphomas/leukemias Flashcards

1
Q

What happens to B cells if they react with the host, or fail to react with the pathogen?

A

they are induced to die – and their corpses litter the field in the form of macrophages containing remnants of their nuclei. The remnants tend to pick up hematoxyin – they are “tingible bodies.”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

T or F. In general, malignancies which appear to derive from well differentiated cells are less aggressive.

A

T. These are termed chronic leukemias while those dealing with bone marrow precursor cells are termed acute leukemias.

But there are many exceptions.

Another general rule: malignancies which appear to derive from well differentiated cells (chronic) can transform into more aggressive forms (acute).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

If an evil genius wanted to cause a B-cell malignancy, he (or she) would probably start by finding a way to translocate an oncogene to an Ig promoter. This is a key pathogenetic point and you need to know it.

A

It is highly likely that B and T cells precursors are predisposed to this type of cancer-causing translocation because somatic DNA recombination is an essential part of their development.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

T or F. Most lymphoproliferative diseases manifest themselves in more than one organ system.

A

T. If the bloodstream is the predominant target, we use the term “leukemia.” If not, we use the term “lymphoma”.

In many cases the two overlap.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens in follicular lymphoma?

A

an oncogene (Bcl-2) translocates to an Ig promoter, leading to overexpression, and subsequent lymphoproliferative disease occurs primarily in lymph nodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is another example of a lymphoproliferative disease that involves a translation of an oncogene to an Ig promoter?

A

Burkitt’s lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is an example of a lymphoproliferative disease that does NOT involves a translation of an oncogene to an Ig promoter?

A

Chronic lymphocytic Leukemia (small lymphocytic lymphoma)

aka CLL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

CLL derives mainly from what cell?

A

from the most mature forms of B-cells. Most of those are inactive “memory B-cells”. Some are found in the “marginal zone”, a poorly defined region just outside the mantle zone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Clinical presentation of CLL?

A

lymphocytosis in older males. High familial incidence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the main sites affected in CLL?

A

peripheral blood more than bone marrow, lymph nodes

in peripheral blood you will see small lymphocytes with little cytoplasm called “smudge” cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How is CLL diagnosed?

A
  • peripheral smear
  • confirmed by immunophenotyping (flow cytometry).

Again, the patient’s lymphocytes are small with scant cytoplasm and mature (dense) chromatin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is unique about the appearance of lymph nodes in CLL?

A
  • characteristic “pseudofollicular” appearance in lymph nodes.
  • The pseudofollicles appear to be collections of slightly larger cells which are undergoing DNA synthesis and mitosis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What abnormalities are normal in cytogenetic analysis of CLL?

A

80% show abnormalities by FISH

most common to least:

  • del13q14.3
  • trisomy 12
  • del11q22-23, del17p13(p53 region)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Immunophenotype of CLL?

A

Light chain restricted (kappa or lambda),

CD20 weak,

CD5+, CD23+

ZAP-70, CD38 (presence of bad= bad prognosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Does a 17p deletion indicate a good or bad prognosis in CLL? What about 13q?

A

17p (deletes p53)= BAD

13q- better

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are some other prognostic markers in CLL?

A
  • presence of >30% smudge cells (good)
  • an increasing fraction of immature forms (“prolymphocytes”; bad)
  • immunophenotypic markers
  • certain genetic features.

Again: P53 (located on 17p) is a bad player in a number of malignancies and is a part of your genome with which you should become intimately familiar.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

CLL is common, and at diagnosis you must distinguish it from a more aggressive lymphoproliferative disease with some similar properties: _______

A

Mantle cell lymphoma

normal counterpart: mantle cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is a key difference between CLL and MCL?

A

no proliferation centers in the lymph nodes in MCL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Clinical presentation of MCL?

A

Lymphadenopathy and/or Lymphocytosis in older males.

Can look clinically like CLL at presentation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the main sites affected in MCL?

A

lymph nodes more than bone marrow, spleen, peripheral blood, and GI tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Morphology of MCL?

A

peripheral blood: small lymphocytes with little cytoplasm (aka smudge cells)

Lymph nodes: usually homogeneous effacement , ‘starry sky’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Immunophenotype of MCL?

Important here

A

light chain restricted (kappa or lambda)

CD5+

CD20 strong, CD23-*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What genetic defect in common in MCL?

A

t(11;14)(q13;q32) (IgH;Cyclin D1) is ALWAYS seen BY FISH

translocation of an oncogene to the IgH promoter

Overexpression of cyclin D1 (CCND1) pushes the cell through the cell cycle (G1 phase to S-phase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Is CML more or less aggressive than CLL?

A

more

key clinical predictors: Ki-67 immunization (mitotic rate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is normal counterpart in Burkitt lymphoma (sporadic)?

A

memory B cells

same in endemic Burkitt lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Clinical presentation of Burkitt lymphoma (sporadic)?

A

abdominal mass in children or young adults. Higher incidence in HIV+ individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Primary involved sites in Burkitt lymphoma (sporadic)?

A

ileo-cecal area/ ovaries/kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Morphology of Burkitt lymphoma (sporadic)?

A

intermediate sized lymphocytes with very blue (basophilic) cytoplasm, unusual cytoplasmic vacuoles, and more variation in nuclear size and shape than we see in the low grade lymphomas like CLL/SLL. (same in endemic BL)

The cells are growing fast, and they die fast too - with the dead cells being taken up by macrophages scattered around in the tumor (the large cells with clear cytoplasm, which at low power make the tumor look like a ‘starry sky’). You can see dark fragments of dead nuclei in some of the macrophages. usually homogeneous effacement in tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Clinical presentation of endemic Burkitt lymphoma?

A

Jaw/facial bone mass in a child (age 4-7) in a p. falciparum malaria-endemic area (Ghana, Papua New Guinea)

30
Q

In central africa and in Papua New Guinea, the tumor is more common, presents in a different anatomic location, and is the most common cancer in kids. We call it, in this context, “endemic Burkitts”, and the tumor cells usually contain EBV (yes, that EBV, the one that causes infectious mononucleosis).

A

EBV can clearly contribute an effective oncogene (It’s a DNA virus with a big genome full of products that can maximize DNA replication), but that alone doesn’t explain this type of lymphoma.

We know that malaria (and specifically, p. falciparum malaria) contributes, but the mechanism connecting EBV, malaria, and this lymphoma is still not clear.

31
Q

Immunophenotype of endemic OR sporadic BL?

A

typical B cell markers (CD10, CD19, CD20)

32
Q

Pathogenesis of BL (sporadic and endemic)?

A

translocation of MYC (on 8q24) to an Ig promoter:

either to IgH (14q32) OR to kappa light chain (2p12) OR to lambda light chain (22q11)

so translocations could be: (8,14), (8,2), OR (8,22)

33
Q

Plasma cell neoplasms are common in what patient population?

A

the elderly.

34
Q

What are the major affected sites in plasma cell neoplasms?

A

bone marrow WAY more than peripheral blood

35
Q

Lab findings of plasma cell neoplasms?

A

in mild forms might see the presence of Reuleaux (little stacks of red cells) in peripheral smear

and increased total protein levels

36
Q

Clinical presentation of plasma cell neoplasms? Mild vs. severe

A

common in older patients

mild forms: asymptomatic lab findings (monoclonal gammopathy of uncertain signifcance, MGUS)

severe forms: Multiple lytic bone lesions (plasma cell myeloma); pain, fractures, renal failure

37
Q

What is you followup after seeing increased serum protein levels?

A

The lab can then help you make the diagnosis by electrophoresing the (non-reduced, non-denatured) serum proteins.

Most labs will “reflexively” identify any abnormal single protein species via IFE.

38
Q

What happens in an IFE?

A

In IFE, six identical lanes of serum proteins are run and transferred to a solid support matrix. They are then visualized with a reagent that stains most proteins (ELP) or reagents that stain particular types of immunoglobulin proteins.

In normals, all of the immunoglobulin lanes show up as smears, collections of polyclonal immunoglobulins. When a clone secreting a single immunoglobulin is present, a single band (in this case, made up of monoclonal IgG kappa antibodies) is seen.

39
Q

How do plasma cells appear?

A
  • lot of cytoplasm, and a nucleus located off to one side of the cell (“eccentric”).
  • clumpy chromatin in their nuclei
  • large, obvious golgi apparati in the cytoplasm – usually evident as a perinuclear clear space that early hematopathologists called a “hof” (a house’s yard, in German).
40
Q

Large collections of plasma cells in bone marrow tend to do what?

A

erode bone– and to leave radiologically evident bone lesions (hence the term multiple myeloma).

41
Q

Immunophenotype of plasma cell neoplasms?

A

CD38+++, CD138+++,

CD19/CD20-

light chain restricted

42
Q

Genetics of plasma cell neoplasms?

A
  • Translocation of IgH to various oncogenes (FISH) in about 2/3 of cases.
  • Trisomies (hyperdiploidy) of ODD NUMBERED CHROMOSOMES are common
43
Q

Clinical courses of the different types of plasma cell neoplasms?

A

MGUS: 1%/yr progress to MM

Multiple myeloma: Median survival is 3-4 yrs

44
Q

What are some key negative prognostic markers in plasma cell neoplasms?

A

Serum beta 2 microglobulin

t(4;14) FGFR3
t(14;16) C-MAF
t(14;20) MAFB
del 17p (p53 region)

45
Q

What is critical to the pathogenesis of follicular lymphoma?

A

Failure of germinal center B-cells to apoptose (because they overexpress an anti-apoptotic protein, Bcl-2)

And that happens via our recurring theme, translocation of an oncogene to an IgH promoter region.

46
Q

What do the lymph nodes look like in follicular lymphoma?

A

big, non-tender lymph nodes containing a proliferation of follicles.

47
Q

What do the follicles look like in follicular lymphoma?

A
  • no polarity (large to small cells)
  • no tangible body macrophages
  • ** very low number of mitotic figures** (they are usually high in cancers)
48
Q

What is the clinical presentation of follicular lymphoma?

A

-lymphadenopathy in older individuals (otherwise asymptomatic usually)

49
Q

What sites are most affected in follicular lymphoma?

A

bone marrow involved in 40-70% of cases

can involve peripheral blood

50
Q

Immunophenotype of follicular lymphoma?

A

CD19/CD20/CD10+ (60%)

BCL-2+ (90%)

BCL-6+ (85%)

51
Q

Genetics of follicular lymphoma?

A

t(14;18)(14q32;18q21)+ in >85%)

It is translocated to an IgH promoter region in most – but not all – FL cases.

Multiple other translocations/deletions can occur

52
Q

Clinical course of follicular lymphoma?

A

Depends on stage, grade, and cytogenetics

30% progress eventually to diffuse large B-cell lymphoma

53
Q

How is FL graded?

A

Pathologists grade FL on the basis of how many large cells (centroblasts) are present. That does predict prognosis.

grade 1= mostly centrocytes (small, dark)

grade 3= mostly centroblasts (larger)

54
Q

Diffuse large B-cell lymphoma is a large category defined primarily by what?

A

morphology only (kind of a garbage can category for loosely defined B cell lymphomas)

25-30% of B-cell lymphomas

55
Q

Clinical presentation of diffuse large B-cell lymphoma?

A
  • rapidly growing adenopathy

- presents in elderly patients

56
Q

40% present of patients with diffuse large B-cell lymphoma present with what?

A

extranodal disease (GI tract, bone marrow, other)

57
Q

Immunophenotype of diffuse large B-cell lymphoma?

A

CD19/CD20/CD10 (30-60%)

58
Q

Genetics of diffuse large B-cell lymphoma?

A

t(v, 3q27)(v, BCL-6) in ~30%;

t(14;18) in 20-30%

Multiple other translocations/deletions can occur

59
Q

How does Hodgkin lymphoma present? population?

A
  • Males, age 30-50

Localized or diffuse adenopathy

Often with involvement of cervical, mediastinal,
or abdominal lymph nodes, and/or spleen

60
Q

What are Reed/Sternberg cells seen in HL?

A

Large lymphoid cells with mono- or bi-nucleate appearance, huge eosinophilic nucleoli; overall horseshoe shape is likely

Diverse background cells: small lymphocytes, plasma cells, eosinophils, neutrophils, histiocytes

61
Q

Are Reed/Sternberg cells specific to HL?

A

No, Very similar cells can be seen in some reactive conditions, such as mononucleosis.

62
Q

What are the subtypes of HL?

A

1) Classical hodgkin lymphoma

2) Nodular lymphocyte predominant Hodgkin Lymphoma

63
Q

How are the Reed/Sternberg cells different in NLPHD?

A

they are small with less prominent nucleoli

They sometimes show large, densely staining nuclei with little cytoplasm, which pathologists refer to as ‘mummified’ forms.

64
Q

What are R/S cells?

A

Reed Sternberg cells are B-cells which went into germinal centers expecting to die. But they acquired anti-apoptotic mutations, such as constitutive NFkB expression, mutation from EBV infection, or others that prevents it.

DO NOT express surface immunoglobulins due to “crippling” Ig promoter/transcription factor mutations

There is reason to think they acquired some genetic instability early in the process.

65
Q

Immunophenotype of classical HL?

A

Flow cytometry not currently useful (RS cells too fragile, few)

CD30+ (>90%),
CD15+ (>80%),
Pax5+ (>90%) (B-cell transcription factor)
CD20-/weak

66
Q

Clinical course of classical HL?

A

Curable with chemo/RT

97% 10-yr survival

67
Q

How are R/S cells different in NLPHD compared to CHL?

A

they do express surface immunoglobulins (i.e.No “crippling” Ig promoter/transcription factor mutations)

everything else is the same about them

68
Q

Is the clinical presentation of NLPHD different than CHL?

A

Nope, they are similar

69
Q

What is different about the morphology of nodular hodgkins vs. classical?

A
  • Nodular, with mostly lymphocytes in the background
  • BUT with “popcorn” cells (lympho-histocytic “L&H” cells) in place of classic RS cells

Morphology alone is NOT sufficient to make the diagnosis

70
Q

Immunophenotype of NLPHD?

A

(L&H cells):
Flow cytometry not currently useful (RS cells too fragile, few)

CD30- (~80%),
CD15- (~100%),
Pax5+ (>95%%) (B-cell transcription factor)
CD20+ (>95%)

T-cells ‘ringing’ the R/S cells

71
Q

Clinical course of NLPHD?

A

80% 10-year survival

Treatment at Stage 1 may not be needed

3-5% progression to diffuse large B-cell lymphoma

Heme Week 2 (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions