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Hematalogy Lecture > Unit 3: Lymphomas and Plasma Cell Disorders > Flashcards

Unit 3: Lymphomas and Plasma Cell Disorders Flashcards

1
Q

What region of the lymph node focus of B-cell proliferation (germinal centers)

A

Cortex

-Cortical nodules (arranged in circles in outer cortex)

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2
Q

Lymph node medulla has medullary cords (____ lymphs and plamsa cells)

A

B

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3
Q

What area of the lymph nodes contains T cells and macrophages?

A

Paracortex (between the medulla and cortex)

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4
Q

Naïve B lymphs express what CD markers?

A

CD 19, 20, and 5

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5
Q

T cells express what CD markers?

A

(CD3,5,2,7) w/ CD4
and CD8

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6
Q

CD 10 is found in…

A

mature B-cells

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7
Q

All CD 20 except…

A

T-cells?

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8
Q

Lymph node functions:

  • Role in the formation of new ___ lymphocytes from germinal centers
  • Involved in the processing of specific immunoglobulins
  • Involved in the filtration of matter, debris, and bacteria
A

B

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9
Q

Lymph Node Processing:

  • Specimen is transported to Pathology laboratory…..kept moist
  • Sliced into ___mm-thick sections
  • Touch imprints are made
  • Thin sections are sliced and preserved
  • Portion is sent to flow cytometry, and the rest in frozen in -70°C for further
    studies
A

3

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10
Q

True or Flase:

Most lymphomas develop in previously healthy people.

A

true

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11
Q

strongest risk factor for developing lymphoma

A

altered immune function
-Also a link to chemical exposure

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12
Q

Lymphomas subtypes are distinguished based on…

A

morphology,
immunophenotype, molecular characteristics, and clinical characteristics – all are mandatory for
comprehensive lymphoma diagnosis

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13
Q

General characteristics of lymphomas:

Hallmark signs…

A

histology is abnormal, destructive lymph
node enlargement

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14
Q

True or false:

lymphoma diagnosis requires lymph node biopsy

A

True!

-Typically no abnormal cells seen in p.b. until late in disease course (progression to a leukemia)

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15
Q

What is it called when lymphoma progress to the p. b.?

A

peripheralization stage (going towards leukemia)

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16
Q

Lymphomas can be divided into what two categories?

A
  1. Mature B cell lymphomas
  2. Mature T cell lymphomas
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17
Q

What are the two major types of lymphomas?

A

-Hodgkin’s Lymphoma (HL)
-Non-Hodgkin’s Lymphoma (NHL)

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18
Q

Two Major Types of Lymphomas:

Which is more common?
Which is more common in kids?

A

Non-Hodgkin’s Lymphoma (NHL)
-especially in autoimmune pts

Hodgkin’s Lymphoma (HL) more common in kids

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19
Q

Two Major Types of Lymphomas:

Which has a leukemic phase (cleaved lymphocytic nuclei)?

A

Non-Hodgkin’s Lymphoma (NHL)

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20
Q

Two Major Types of Lymphomas:

Pleomorphic cells, some normal, some malignant

A

Hodgkin’s Lymphoma (HL)

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21
Q

Two Major Types of Lymphomas:

Uniform, malignant cells

A

Non-Hodgkin’s Lymphoma (NHL)

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22
Q

Two Major Types of Lymphomas:

Accurate staging crucial to treatment!

A

Hodgkin’s Lymphoma (HL)

-Unifocal origin with predictable spread along lymph node chain

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23
Q

Two Major Types of Lymphomas:

Multifocal origin with unpredictable spread

A

Non-Hodgkin’s Lymphoma (NHL)

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24
Q

Hodgkin’s Lymphoma (HL):

Malignant cell =

A

Reed-Sternberg cell (distinctive, multi-nucleated, & giant-sized; called “owl-eyes”) or a variant of this cell

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25
Q

Non-Hodgkin’s Lymphoma (NHL):

Malignant cell =

A

B lymph in 95% of cases; T lymph in remaining cases, & rarely, even NK cell

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26
Q

Two Major Types of Lymphomas:

Which has good prognosis if still localized (>90% cure)?

Which is worse prognosis?

A

Hodgkin’s Lymphoma (HL)

Non-Hodgkin’s Lymphoma (NHL)

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27
Q

What are the symptoms of Hodgkin Lymphoma?

A
  • Painless, enlarged cervical lymph nodes
  • Sometimes mediastinal mass between lungs.
  • “B symptoms” = fever, weight loss, night sweats (poor prognostic indicator)
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28
Q

Hodgkin lymphoma and Non-Hodgkin’s Lymphoma (NHL) are _______-geneous group of disorders

A

hetero-

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29
Q

Hodgkins lymphoma:

Untreated patients die ____ years after onset due to recurrent infections & organ failure.

A

1-2

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30
Q

Hodgkin lymphoma can be divided into what two groups?

A
  • Nodular Lymphocyte-Predominant Hodgkin Lymphoma
  • Classical Hodgkin Lymphoma
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31
Q

Hodgkin lymphoma group:

B cell neoplasm w/ rare neoplastic cells (popcorn cells)

A

Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

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32
Q

Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) cells are positive for CD___ and CD___.

A

20, 45

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33
Q

Reed Sternberg (RS) cells are also known as…

A

owl eyes

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34
Q

Characteristic Reed-Sternberg (RS) cell (or variant) found in lymph nodes, but virtually never found in p.b.

A

Classical Hodgkin Lymphoma***

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35
Q

What must be seen with Hodgkin’s lymphoma to establish diagnosis?

A

Reed-Sternberg (RS) cells!

-Huge! 4-8X size of normal lymph
- Typical large, eosinophilic dual nucleus (“binucleated”), with distinctive surrounding halo (“owl-eyed”).

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36
Q

Reed-Sternberg (RS) cells are ***CD ___+ in all cases, CD___+ in 80% of cases.

A

30

15

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37
Q

Why is it important to stage HL?

A

Essential to accurately stage disease to determine treatment & prognosis! Numerous diagnostic tests used: bone scans, thoracic CT scans, immunophenotyping, routine labs, & both lymph node & liver biopsies.

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38
Q

HL treatment?

A

Radiation & chemo. can effect 90% cure rate if disease is localized! Treatment success judged by degree of reversal of
lymph node dysplasia. However, therapy can cause secondary cancer later on!

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39
Q

How does NHL present?

A

with painless cervical lymph node enlargement, but typically at a more advanced stage.*

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40
Q

Pre-existing NHL causes ↑ risk of developing…

A

a combined B & T Cell disorder by 10,000X

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41
Q

What are the 3 combined B & T cell disorders?

A

Wiskott-Aldrich, SCID, & ataxia telangiectasia (AT)

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42
Q

NHL overall has strong association with _____ proto-oncogene rearrangement on chromosome ___

A

cmyc, 8

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43
Q

_____ is a transcription factor for cell growth found to be over-expressed
in many different kinds of malignancies

A

cmyc

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44
Q

NHL lab findings:

Mostly N. p.b. cell morphology, but may see…

A

cleaved nuclei in lymphs

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45
Q

Ture or false:

NHL typically does have a leukemic presentation at the end stage of the disease.

A

true

46
Q

________ Grade NHL - affects 45-60 yrs. old; slow-growing, survival with treatment 5 - 7 yrs

A

Low

47
Q

_____________ grade NHL - affects 45-60 yrs. old; more rapid enlargement & more common extra-nodal disease. (FYI: frequently the Diffuse Large B Cell Lymphoma subtype.)

A

Intermediate

48
Q

_______ grade NHL - rapidly growing nodes; often rapidly
fatal even with therapy.

A

High

49
Q

NHL treatment?

A

Similar to that of HL:
Radiation
Chemotherapy

50
Q

Mature B cell lymphomas:

  • Derived from various stages of B cell differentiation
  • All produce ____________
    immunoglobulins, clonal immunoglobulin gene
    rearrangements, or both
A

monoclonal light chain***

51
Q

Mature B cell lymphomas:

Most cases are _________-based and occur in elderly individuals

A

lymph node

52
Q

What are the types of Mature B cell lymphomas?

A
  • CLL/SLL (small lymphocyte lymphoma)
  • Mantle cell lymphoma
  • Follicular lymphoma
  • Diffuse large B cell lymphoma
  • Burkitt lymphoma
53
Q

Small Lymphocytic Lymphoma/CLL:

-Diffuse proliferation of small hypermature (“soccer-ball”) lymphoid cells and smudge cells
-Derived from what circulating cells?

A

IgM, IgD, B-cells

54
Q

Small Lymphocytic Lymphoma/CLL:

Both types (naïve B and memory B cells) are positive for CD,,,

A

D19, CD 20, and CD23 (+/- CD5)

55
Q

Median survival for Small Lymphocytic Lymphoma/CLL?

A

10 years

56
Q
  • Diffuse proliferation of medium-sized cells w/ irregular nuclear
    outlines
  • Peripheral blood can mimic PLL
A

Mantle Cell Lymphoma

57
Q

Mantle Cells are positive for CD…

A

CD5, CD19, CD20; but negative for CD23**

58
Q

Mantle cell Lymphoma is linked to t(_____) defect

A

t(11;14)

59
Q

Median survival for Mantle Cell Lymphoma?

A

3 to 5 years

60
Q

Nodular proliferation replaces N. architecture

A

Follicular Lymphoma

61
Q

Follicular Lymphoma:

Originates in ________ and involves neoplastic proliferation of medium-sized cells, mixed w/ large lymphoid cells.

A

germinal centers

62
Q

How is Follicular Lymphoma graded?

A

3 grades = graded by counting the average number of large cells observed per hpf

63
Q

True or false:

Follicular Lymphoma cells have an increased sensitivity to apoptosis?

A

False, decreased

64
Q

Follicular Lymphoma cells are positive for CD…

A

CD19 and CD20

65
Q

Follicular lymphoma is linked to t(_____) and (______)

A

t(14:18) and (q32;q21)

66
Q

> 95%. Follicular Lymphoma Express ______ protein – decreased apoptosis sensitivity.

A

BCL-2

67
Q

Follicular Lymphoma:

____% of cases see bone marrow involvement

A

50

68
Q
  • Diffuse proliferation of large lymphocytes (twice the size of normal lymphs)
  • Most common lymphoma (30-40%)
A

Diffuse Large B Cell Lymphoma
(DLBCL)

69
Q

Diffuse Large B Cell Lymphoma (DLBCL) cells are positive for CD…

A

D5, CD10, CD30, and CD138

70
Q
  • Rarely observed in children
  • Rarely extends to bone marrow
  • Survival rate is increasing – varies upon severity
A

Diffuse Large B Cell Lymphoma (DLBCL)

71
Q

What pattern can be observed with macrophages in Burkitt Lymphoma?

A

“starry sky”

72
Q

Mass proliferation of medium-sized cells with basophilic vacuolated cytoplasm

A

Burkitt Lymphoma

73
Q

Burkitt Lymphoma:

Cells are positive for CD…

A

CD10, CD19, and CD20

74
Q

Burkitt Lymphoma:

Linked to MYC gene t(____), t(_____), and t(_____) causing varying degrees of severity

A

(t[8;14], t[2;8], t[8;22])

75
Q
  • Diagnosis is considered a medical emergency
  • Treatment is highly aggressive and helps keep cure rates high
A

Burkitt Lymphoma

76
Q

Mycosis Fungoides & Sezary Syndrome:

Both are _____________ (just different stages of the same neoplasia!)***

A

cutaneous T-cell lymphomas

77
Q
  • Mature T-helper cell (CD4+) lymphoma.
  • Cells produced in lymphatic tissues, then migrate to skin!
  • Highly aggressive.***
A

Mycosis Fungoides & Sezary Syndrome

78
Q

Mycosis Fungoides & Sezary Syndrome pts are usually…

A

middle-aged males.

79
Q

What is the most common cutaneous lymphoma?

A

Mycosis fungoides*

80
Q

What is the skin presentation stage of Mycosis fungoides?

A
  • Typically see pruritus, followed by weepy erythroderma.
  • Then whitish plaques form
  • Finally, nodular tumors occur (very indolent course until end of the disease).
  • Disease progresses from skin to organ involvement.
  • After organ involvement, survival is just a few months if treatment is not instituted.
81
Q

What is the prognosis for Sezary syndrome with p.b. presentation stage?

A

bad prognosis by now

82
Q

Are “butt cells” highly specific for just Sezary?

A

no, seen in other lymphoid neoplasms

83
Q

What are the lymphocytes in Sezary syndrome?

A

Lymphocyte here called Sezary cell:
* Larger lymph than N.
* Scant cytoplasm
* Large, uniquely cleaved nucleus:
* May be cleaved (“butt cell”)

84
Q

Mycosis Fungoides & Sezary Syndrome treatment?

A
  • Topical chemo. & superficial radiation for mycosis fungoides.
  • Regular radiation & chemo. if disease has progressed to organ involvement.
85
Q

HIV infection increases general lymphoma risk (by ~____X).
* Many types (NHL, HL, Burkitt’s, etc.) may occur, especially late in AIDS.
* Usually very aggressive.
* Usually EBV negative.

A

60

86
Q

HIV-Related Lymphoma:

What therapy increases CD4 counts, unfortunately does not ↓ rate of incidence of HIV-related lymphomas?

A

Highly Active Anti-Retroviral Therapy

87
Q

occurs when a tumor of malignant plasma cells overgrows in the bone marrow
* Causes overproduction of a single Ig (synthesis of normal Igs is suppressed).

A

Multiple Myeloma (MM)

88
Q

_____ is the most common malignant disease of plasma cells!***

A

MM

Pts. generally > 40 yrs. old.

89
Q

SPE & urine elp show characteristic monoclonal “spike”, Bence-Jones
proteinuria, and ↑ ESR

A

MM

90
Q

MM lab findings?

A

*Characteristic mod. rouleaux & few abnormal plasma cells in p.b. smear.
* FYI: ↑ [plasma protein] can depress plt. function.

91
Q

What type of anemia do MM pts have?

A

Normo- normo- anemia due to Myelophthisic Anemia

92
Q

MM:

Lytic bone disease seen on bone scans. Patients also can develop amyloidosis: condition in which…

A

amyloid (starch-like protein deposits) are deposited throughout body, causing multiple organ defects*

93
Q

Bone marrow findings with MM?

A

plasma cells that contain Russell bodies (rounded accumulations of Ig in rER), are called Mott cells/grape cells/morula cells.

94
Q

MM:

Plasma cell seen in Ig___ myeloma is called a Flame Cell

A

A

95
Q

MM Clinical Symptoms?

A
  • Painful bone lesions*
  • Pathologic fractures*
  • FYI: These occur bc. plasma cells secrete an osteoclast-activating factor.
  • Weakness & fatigue
  • Renal failure*
96
Q

What is the prognosis for MM?

A

Not curable, but treatable (but poor prognosis
overall)*

97
Q

MM treatment:

what meds are used in various combinations?

A
  • Steroids
  • Chemo. & radiation before stem cell transplant.
  • Aredia – new drug; strengthens bones.
  • Newest med. for MM: Velcade – used for relapsed & refractory MM only.
  • First in new drug class of IV proteasome inhibitors
    -For unknown reason, proteasome inhibition causes more apoptosis
    in malignant cells than in N. cells!
98
Q

-Occurs when absolute # of circulating plasma cells exceeds cutoff (> 2000/uL)
* May occur as end-stage sequela of MM, or by itself.
* Usually found in pts. younger than middle age.

A

Plasma Cell Leukemia (PCL)

99
Q
  • Malignant plasmacytoid lymphocytes
  • Pt. typically male, over 50 yoa.
  • Rarer condition than MM.
A

Waldenstrom’s Macroglobulinemia (WM)

100
Q

Waldenstrom’s Macroglobulinemia (WM):

Abnormally increased CD___ cell surface markers.

A

20***

101
Q

Waldenstrom’s Macroglobulinemia (WM):

  • Oversecretion of Ig___
A

M

102
Q

Malignant plasmacytoid lymphocytes

A

Waldenstrom’s Macroglobulinemia (WM)

103
Q

Waldenstrom’s Lab Findings:
* P.b. smear looks similar to ______

A

MM

104
Q

Waldenstrom’s Lab Findings:

___+ increased ESR
-Slt. Bence-Jones proteinuria

A

4

105
Q

Waldenstrom’s Lab Findings characteristic marked __________ in p.b. smear.

A

rouleaux

106
Q

Automated Heme instrumentation may give spuriously high WBC & plt. counts due to the cryoglobulin activity of IgM – it forms gels & precipitates upon refrigeration!

A

Waldenstrom’s Macroglobulinemia (WM)

107
Q

increased [plasma protein] can ↓ plt. function, same as MM.

A

Waldenstrom’s Macroglobulinemia (WM)

108
Q

Waldenstrom’s Clinical Findings:

A
  • Gradual onset of following as IgM levels increase:
  • Weakness & fatigue
  • Weight loss
  • Epistaxis
  • But no bone lesions – organomegaly instead
109
Q

Waldenstrom’s Treatment:

A
  • Steroids
  • Plasmapheresis and/or chemo.
  • Rituximab, an I.V. monoclonal Ab binds CD20 antigens, & thus flags malignant plasmacytoid lymphs for death!
110
Q

Waldenstrom’s Macroglobulinemia (WM):

Why are CD20 Ags important here?

A

Because they are so highly overexpressed in this disease.

111
Q

Ig produced with MM?

with Macroglobulinemia?

A

IgG > A > D > E

IgM

Hematalogy Lecture (35 decks)

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