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T1 - Phase 2 - Systems Modules (I) > Neoplasia/Hematology - Mechanisms of Disease - Lymphomas > Flashcards

Neoplasia/Hematology - Mechanisms of Disease - Lymphomas Flashcards

1
Q

What are the three ‘B symptoms’ of lymphoma?

A
  1. Night sweats
  2. Fever
  3. Weight loss
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2
Q

What does it mean for a lymphoma to be stage I?

And stage II?

A

Only 1 lymph node involved;

≥2 lymph nodes on the same side of the diaphragm

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3
Q

What does it mean for a lymphoma to be stage III?

And stage IV?

A

≥2 lymph nodes involved with involvement on both sides of the diaphragm;

metastatic disease

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4
Q

What does it mean if a lymphoma is stage Ib (or stage IIb or IIIb or IVb)?

(I.e. what does the ‘b’ mean?)

A

The stage + ‘B symptoms’

(B symptoms = night sweats + fever + weight loss)

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5
Q

What chemo regimen is used for Hodgkin’s lymphomas?

A

ABVD + radiotherapy

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6
Q

What chemo regimen is used for non-Hodgkin’s lymphomas?

A

R-CHOP

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7
Q

Reed-Sternberg cells are positive for what two CD markers in particular?

A

CD15; CD30

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8
Q

What marker would be an indicator that a population of leukocytes examined under flow cytometry are blasts (immature)?

A

CD34

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9
Q

What is a smudge cell?

A

Lymphocytes squished during smear preparation

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10
Q

What heuristic can be used to determine what a patient’s bone marrow cellularity should be?

A

100% - their age

(E.g. a 60 year old woman would have an expected cellularity of ~40%)

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11
Q

Why might you order an echocardiogram on a patient being prepared for treatment for leukemia?

A

Many chemotherapeutic drugs are cardiotoxic

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12
Q

In what way can flow cytometry of light chains be used to determine if there is a monoclonal lymphoproliferation?

A

The normal 3-to-1 kappa:lambda ratio is skewed nearly 100% in one direction

(i.e. all kappa or all lambda)

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13
Q

What is the most common form of leukemia?

What is the median age of diagnosis?

A

CLL

70

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14
Q

What is the most common leukemia seen in children?

And adults?

A

ALL;

CLL

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15
Q

What mutation is common to follicular lymphomas?

What is overexpressed because of this mutation?

A

t(14 ; 18)

Bcl-2

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16
Q

Name the diseases associated with each of the following translocations:

t(8 ; 14)

t(9 ; 22)

t(14 ; 18)

t(11 ; 14)

A

Burkitt lymphoma

CML

Follicular lymphoma

Mantle cell lymphoma

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17
Q

You note that a proliferation of B cells is positive for t(11 ; 14), and it is Sox-11+.

What is the likely diagnosis?

Note: it is also CD5+, CD20+, and CD23-

A

Mantle cell lymphoma

(t(11 ; 14) leads to increased cyclin-D1 expression)

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18
Q

Name a few translocations associated with marginal zone lymphomas.

A

t(11 ; 18)

t(11 ; 14)

t(1 ; 14)

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19
Q

You note that a proliferation of B cells is positive for t(14 ; 18), and it is CD10+.

What is the likely diagnosis?

A

Follicular lymphoma

(increased expression of Bcl-2)

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20
Q

Mantle cell lymphoma is associated with the t(11 ; 14) mutation which increases cyclin-D1 expression. What effect does cyclin-D1 have on the cell?

A

Increased progression of G1 to S

(increased activation of Rb and E2F)

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21
Q

What are the two basic subtypes of acute lymphocytic leukemia?

A

B cell (more common);

T cell

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22
Q

Which type of ALL typically involves the bone marrow?

Which typically presents as a lymphoma of the anterior mediastinum?

A

B-ALL (more common);

T-ALL

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23
Q

How/where does T cell ALL typically present?

A

Lymphoma of the anterior mediastinum

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24
Q

What is the hallmark sign of acute leukemias (ALL; AML) on blood smear examination?

A

Presence of blasts

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25
Q

A 16 year old male presents with easy brusing, pallor, weakness, and vomiting. A workup reveals thrombocytopenia, anemia, and a pronounced increase in WBCs.

You note the presence of many blasts on smear.

How do you quickly differentiate between ALL and AML?

A

ALL — no Auer rods

AML — Auer rods present in blasts

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26
Q

True/False.

Some lymphoproliferative disorders such as CLL may be characterized by monoclonal B cells that are also found on flow cytometry to express some T cell receptors (e.g. CD5) with their B cell receptors.

A

True.

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27
Q

True/False.

CD markers below 10 are characteristic of B cells and CD markers above 10 are characteristic of T cells.

A

False.

CD markers below 10 are characteristic of T cells (e.g. CD1, 2, 3, 4, 5, 8) and CD markers above 10 are characteristic of B cells (e.g. CD19, 20, 21).

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28
Q

What are the differences between CLL, SLL, and MBL?

A
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29
Q

What is necessary for a diagnosis of CLL?

A

B cell count > 5,000

(lymphadenopathy / extranodal disease may or may not be present)

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30
Q

How are CLL and SLL (small lymphocytic leukemia) differentiated on blood analysis?

A

CLL: B cell count > 5,000 (mostly in blood and bone marrow)

SLL: B cell count < 5,000 (mostly in lymph nodes)

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31
Q

What is necessary for a diagnosis of SLL?

A

B cell count < 5,000

+

lymphadenopathy / extranodal disease

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32
Q

What is necessary for a diagnosis of MBL (monoclonal B cell lymphocytosis)?

A

A largely elevated B cell count still < 5,000

(with no lymphadenopathy or extranodal disease — that would make it SLL)

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33
Q

Monoclonal B cell lymphocytosis is a potential precursor to what?

A

CLL

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34
Q

What system is used for classifying the severity of CLL?

A

The Rai system

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35
Q

What can cause thrombocytopenia, anemia, and an increased risk of infection in leukemia patients?

A

Bone marrow out-crowding by proliferating cells

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36
Q

CLL is most common in what age, race, and gender?

A

Older caucasian males

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37
Q

A patient is incidentally diagnosed with CLL. He is currently asymptomatic.

How do you proceed?

A

Do not treat until S/Sy present

(up to 1/3 of patients may not have significant S/Sy before death from other causes)

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38
Q

What are the two main categories of lymphoma?

A

Hodgkin’s;

Non-Hodgkin’s

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39
Q

Hodgkin’s lymphoma is characterized by what cell type?

A

Reed-Sternberg cells

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40
Q

Lymphomas are all characterized by enlargement of what tissue type?

A

Lymphoid tissue

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41
Q

You suspect lymphoma in a patient with swollen lymph nodes.

What is the gold standard for diagnosis?

A

Excisional biopsy

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42
Q

How does a lymph node present when activated?

And when lymphoma is present?

A

Reactive (increase number of germinal centers);

nodular/follicular pattern

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43
Q

Name two methods by which malignant cells can be checked for specific surface molecules.

A

Flow cytometry;

immunohistochemistry

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44
Q

You identify a population of B cells on flow cytometry that are CD5+.

What condition is present?

A

CLL

(CD5 is normally a T cell CD marker)

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45
Q

What system is used for staging lymphomas?

A

The Ann Arbor system

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46
Q

What is the 5-year survival rate for Hodgkin’s lymphoma?

A

87%

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47
Q

What is the most common type of Hodgkin’s lymphoma?

How is its prognosis?

A

Nodular sclerosing;

good

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48
Q

What is the least common type of Hodgkin’s lymphoma?

How is its prognosis?

A

Lymphocyte depleted;

poor

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49
Q

What CD markers are present in classical Hodgkin’s lymphoma?

Which are absent?

A

CD30+ , CD15+

CD20- , CD45-

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50
Q

Classical Hodgkin’s lymphoma makes up ___% of cases.

What type makes up the remainder?

A

Classical Hodgkin’s lymphoma makes up 95% of cases.

nodular lymphocyte predominant Hodgkin’s lymphoma

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51
Q

Name the four main types of classical Hodgkin’s lymphoma in decreasing order of frequency.

  1. ________ ________
  2. ________ ________
  3. Lymphocyte-rich
  4. Lymphocyte-depleted
A
  1. Nodular sclerosis
  2. Mixed cellularity
  3. Lymphocyte-rich
  4. Lymphocyte-depleted
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52
Q

Name the four main types of classical Hodgkin’s lymphoma in decreasing order of frequency.

  1. Nodular sclerosis
  2. Mixed cellularity
  3. ________-________
  4. ________-________
A
  1. Nodular sclerosis
  2. Mixed cellularity
  3. Lymphocyte-rich
  4. Lymphocyte-depleted
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53
Q

Nodular lymphocyte predominant Hodgkin’s lymphoma (responsible for 5% of cases) is characterized by what cell type?

A

Popcorn cells

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54
Q

Reed-Sternberg cells:

CD15__ , CD20__ , CD30__ , CD45__

Popcorn cells:

CD15__ , CD20__ , CD30__ , CD45__

A

Reed-Sternberg cells:

CD15+ , CD20- , CD30+ , CD45-

Popcorn cells:

CD15- , CD20+ , CD30- , CD45+

55
Q

Non-Hodgkin’s lymphomas can first be divided into what two major categories?

A

B-cell derived;

T-cell derived

56
Q

What are the two major categories of non-Hodgkin’s B cell lymphomas?

A

Large cell (aggressive);

small cell (indolent)

57
Q

Which form of leukemia can be classified as either a leukemia or a non-Hodgkin’s B cell lymphoma?

A

CLL (/ SLL)

58
Q

Describe the S/Sy of aggressive (large cell) Non-Hodgkin’s B cell lymphomas:

__________ growing masses

__________ _____ symptoms

Elevated ______

__________ painful lymphadenopathy

A

Describe the S/Sy of aggressive (large cell) Non-Hodgkin’s B cell lymphomas:

Rapidly growing masses

Systemic B symptoms

Elevated LDH

Sometimes painful lymphadenopathy

59
Q

Describe the S/Sy of indolent (small cell) Non-Hodgkin’s B cell lymphomas:

_______ growing masses, _______megaly, cyto_____

_______dious

pain___ lymphadenopathy

A

Describe the S/Sy of indolent (small cell) Non-Hodgkin’s B cell lymphomas:

Slowly growing masses, hepatosplenomegaly, cytopenia

insidious

painless lymphadenopathy

60
Q

These are the S/Sy of __________ (______ cell) Non-Hodgkin’s B cell lymphomas:

Rapidly growing masses

Systemic B symptoms

Elevated LDH

Sometimes painful lymphadenopathy

A

These are the S/Sy of aggressive (large cell) Non-Hodgkin’s B cell lymphomas:

Rapidly growing masses

Systemic B symptoms

Elevated LDH

Sometimes painful lymphadenopathy

61
Q

These are the S/Sy of _______ (______ cell) Non-Hodgkin’s B cell lymphomas:

Slowly growing masses, hepatosplenomegaly, cytopenia

insidious

painless lymphadenopathy

A

These are the S/Sy of indolent (small cell) Non-Hodgkin’s B cell lymphomas:

Slowly growing masses, hepatosplenomegaly, cytopenia

insidious

painless lymphadenopathy

62
Q

Identify which is more likely to be ‘curable’:

Aggressive (large cell) non-Hodgkin’s lymphomas

or

Indolent (small cell) non-Hodgkin’s lymphomas

A

Aggressive (large cell) non-Hodgkin’s lymphomas

(presents much earlier and much more clearly)

63
Q

Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin’s B cell lymphoma?

Mantle cell lymphoma

A

Small cell (indolent) non-Hodgkin’s B cell lymphoma

64
Q

Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin’s B cell lymphoma?

Hairy cell leukemia

A

Small cell (indolent) non-Hodgkin’s B cell lymphoma

65
Q

Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin’s B cell lymphoma?

Marginal zone lymphoma

A

Small cell (indolent) non-Hodgkin’s B cell lymphoma

66
Q

Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin’s B cell lymphoma?

Follicular lymphoma

A

Small cell (indolent) non-Hodgkin’s B cell lymphoma

67
Q

Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin’s B cell lymphoma?

Lymphoplasmacytic lymphoma

A

Small cell (indolent) non-Hodgkin’s B cell lymphoma

68
Q

Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin’s B cell lymphoma?

Chronic lymphocytic leukemia / small lymphocytic leukemia

A

Small cell (indolent) non-Hodgkin’s B cell lymphoma

69
Q

Describe the similar presentations for all small cell lymphomas according to age, gender, expansion of monoclonal cells (involved markers?), and bodily locations.

A

Older males;

monoclonal Smlg+ (mature) B cells

Variably, blood and bone marrow

70
Q

True/False.

Small cell lymphomas are proliferations of immature B cells.

A

False.

Small cell lymphomas are proliferations of mature B cells.

71
Q

Name two proliferative diseases of B cells that express CD5.

A

CLL (/ SLL);

mantle cell lymphoma

72
Q

Which is the most aggressive of the small cell non-Hodgkin’s lymphomas that has a poor survival rate?

A

Mantle cell lymphoma

73
Q

What are the two most common forms of non-Hodgkin’s lymphoma?

A
  1. Diffuse large B cell lymphoma
  2. Follicular lymphoma
74
Q

Small lymphocytes are similar in size to what?

75
Q

What disease is associated with the leukocytes in this image?

A

Follicular lymphoma

(known as cleaved cells or ‘butt cells’)

76
Q

Hairy cell leukemia is typically seen in what patient population?

(Age — race — gender)

A

Middle-aged caucasian men

77
Q

Hairy cell leukemia is relatively _______ (common/rare).

A

Hairy cell leukemia is relatively rare.

78
Q

What mutation leads to hairy cell leukemia?

A

BRAF

(specifically, the V600E variant also seen in melanoma)

79
Q

Hairy cell leukemia is positive for what distinguishing clusters of differentiation?

Are there any other distinguishing molecules that are expressed?

A

CD11c, CD25, CD103;

TRAP

80
Q

A 49 year old caucasian male presents with splenomegaly and you note pancytopenia on lab results. A peripheral smear shows the cell type in the attached image.

Further testing reveals that these cells are positive for a BRAF mutation, and they are also CD5-, CD10-, CD11c+, CD25+, CD103+, and TRAP+.

What is the likely diagnosis?

A

Hairy cell leukemia

81
Q

How will a bone marrow aspirate appear in a patient with hairy cell leukemia?

A

Dry tap

(reticulin fibrosis and diffuse infiltrate on biopsy)

82
Q

Name the one lymphoma type that is associated with any of the following:

Hashimoto’s disease (thyroid lymphoma) (MALT)

H. pylori (MALT)

Sjogren’s syndrome (salivary glands) (MALT)

A

Marginal zone lymphoma

83
Q

Marginal zone lymphomas are a heterogenous group of proliferative disease that typically arise in the ____nodal ________ tissues (MALT); the ________; and _________ _________.

A

Marginal zone lymphomas are a heterogenous group of proliferative disease that typically arise in the extranodal lymphoid tissues (MALT); the spleen; and lymph nodes.

84
Q

True/False.

Marginal zone lymphomas (e.g. MALT) often remain localized and sometimes regress if the inciting agent (e.g. H. pylori) is removed.

85
Q

True/False.

Marginal zone lymphomas are typically CD5- and CD10-.

86
Q

What is lymphoplasmacytic lymphoma?

A

Malignant B cells differentiating into plasma cells

87
Q

Lymphoplasmacytic lymphomas that hypersecrete IgM (a type of macroglobulin) are known by what name?

This hypersecretion may lead to what?

A

Waldenstrom’s macroglobulinemia;

hyperviscosity syndrome

88
Q

Waldenstrom’s macroglobulinemia is a particular type of __________ lymphoma where hypersecretion of ____ (a type of macroglobulin) leads to hyperviscosity.

A

Waldenstrom’s macroglobulinemia is a particular type of lymphoplasmacytic lymphoma where hypersecretion of IgM (a type of macroglobulin) leads to hyperviscosity.

89
Q

Lymphoplasmacytic lymphomas are associated with what infectious agent?

A

Hepatitis C

90
Q

True/False.

The hypoviscosity in some lymphoplasmacytic lymphomas (Waldenstrom’s macroglobulinemia) can lead to blindness, bleeding, neurological issues, and thermoglobulinemia (where IgM precipitates at warm temperatures, leading to Raynaud’s phenomenon and urticaria).

A

False.

The hyperviscosity in some lymphoplasmacytic lymphomas (Waldenstrom’s macroglobulinemia) can lead to blindness, bleeding, neurological issues, and cryoglobulinemia (where IgM precipitates at cold temperatures, leading to Raynaud’s phenomenon and urticaria).

91
Q

How can monoclonal antibody production (e.g. in Waldenstrom’s macroglobulinemia or multiple myeloma) be easily diagnosed?

A

Serum protein electrophoresis

(clear M spike)

(SPEP)

92
Q

What is the most common type of non-Hodgkin’s lymphoma?

A

Diffuse large B cell lymphoma

93
Q

True/False.

Diffuse large B cell lymphomas are often associated with MYC or Bcl-2 mutations.

94
Q

True/False.

Diffuse large B cell lymphoma often follows a fairly standard course with little variability.

A

False.

Many presentations (e.g. primary mediastinal, intravascular, primary effusion, primary cutaneous,

95
Q

What are the two main categories of diffuse large B cell lymphoma?

  1. _______ B-cell-like
  2. _______ B-cell-like
A
  1. Germinal center B-cell-like
  2. Activated B-cell-like
96
Q

Burkitt lymphoma is typically a(n) ______ aggressive, ______-grade malignancy.

A

Burkitt lymphoma is typically an extremely aggressive, high-grade malignancy.

97
Q

Where is Burkitt lymphoma endemic?

A

Equatorial Africa

98
Q

Where do most Burkitt lymphoma tumors typically arise on the body?

A

The jaw / face

99
Q

What lymphoma is associated with EBV?

A

Burkitt lymphoma

100
Q

True/False.

Burkitt lymphoma is basically a mature version of ALL.

101
Q

A man presents with large masses in his jaw and face. The cells in the masses are large lymphocytes with plentiful vacuoles (image attached below), and nearly all (~99%) are positive for Ki-67 (a marker of active cell proliferation). The cells are CD10+ and a t(8 ; 14) mutation is present.

The histology from the biopsies will appear with what general characteristic appearance?

A

‘Starry sky’ appearance

(Burkitt lymphoma)

102
Q

What translocation is associated with Burkitt lymphoma?

The cells will be CD5___

The cells will be CD10___

A

t(8 ; 14)

The cells will be CD5-

The cells will be CD10+

103
Q

The t(8 ; 14) mutation seen in Burkitt lymphoma leads to creation of what oncogene?

104
Q

An unclassifiable lymphoma with characteristics of Hodgkin’s and diffuse large B cell lymphomas is known as what?

A

A gray zone lymphoma

105
Q

A ‘triple-hit’ lymphoma is a highly aggressive, high-grade B cell lymphoma with what mutations?

A
  • MYC*
  • Bcl-2*
  • Bcl-6*
106
Q

What immunodeficiency-related lymphoproliferative disorder develops as a result of immunosuppression following transplant (solid organ, bone marrow, or stem cells) + infection with EBV?

A

Post-transplant lymphoproliferative disorder

(begins as mononucleosis-like lesions –> leads to B and T cell lymphomas)

107
Q

The S/Sy of T cell large granular lymphocytic leukemias often present as:

A_________tic / ________ course

______megaly

_______cytosis

_______penia

A

The S/Sy of T cell large granular lymphomas often present as:

Asymptomatic / indolent course

Splenomegaly

Lymphocytosis

Neutropenia (may also be anemic)

108
Q

Rheumatoid arthritis is associated with what lymphoma?

A

T cell large granular lymphocytic leukemia

109
Q

Adult T cell leukemia/lymphoma is most common in what geographic regions?

A

Japan;

West Africa;

the Caribbean

110
Q

True/False.

Adult T cell leukemia/lymphoma follows a relatively benign course and has no cutaneous lesions.

A

False.

Adult T cell leukemia/lymphoma follows a relatively aggressive course and has cutaneous lesions.

111
Q

Adult T cell leukemia/lymphoma often causes what bone or skin or serum abnormalities?

A

Osteolytic lesions;

cutaneous lesions;

hypercalcemia

112
Q

Adult T cell leukemia/lymphoma is associated with what infectious agent?

113
Q

Nasopharyngeal NK or T cell lymphomas are most common in what geographic region(s)?

How does they typically present?

A

Asia;

aggressive, destructive nasopharyngeal mass (often midline)

114
Q

True/False.

T cell lymphomas are often aggressive and difficult to treat.

115
Q

What is mycoses fungoides (/ Sézary syndrome)?

What specific cell type is involved?

A

A T cell lymphoma that causes cutaneous lesions;

CD4+ cells

116
Q

What is the basic progression of the lesions seen in mycosis fungoides?

A

Patch –> Plaque –> Tumor

117
Q

The T cells in mycosis fungoides are unique in that they are CD__+ and CD__-.

A

The T cells in mycosis fungoides are unique in that they are CD4+ and CD7-.

118
Q

True/False.

Mycosis fungoides is typically indolent but progressive.

119
Q

What is the most common form of T cell lymphoma?

In what gender is it more common?

A

Peripheral T cell lymphoma;

males (2:1)

120
Q

Anaplastic large cell lymphomas are rare and typically CD___+.

They are often characterized by a t(__ ; __) mutation.

A

Anaplastic large cell lymphomas are rare and typically CD30+.

They are often characterized by a t(2 ; 5) mutation.

121
Q

True/False.

Anaplastic cell lymphomas are often aggressive, ALK+, present in older adults, and they typically respond poorly to chemotherapy.

A

False.

Anaplastic cell lymphomas are often aggressive, ALK+, present in children/young adults, and they typically respond well to chemotherapy.

122
Q

Multiple myeloma is a neoplasm of what cell type?

A

Plasma cells

123
Q

What are the main S/Sy of multiple myeloma?

A

CRAB

HyperCalcemia

Renal dysfunction

Anemia

Bone pain

124
Q

Where are the proliferating plasma cells of multiple myeloma typically found?

A

Colonizing the bone marrow

125
Q

The immunoglobulins secreted by multiple myeloma cells are referred to as what?

A

The M component

126
Q

True/False.

The M component of multiple myeloma is mostly associated with elevated IgG levels, but it can be any of the following: IgG, IgA, IgM, or just light chains.

(Note: the M component is a homogenous secretion — i.e. a particular case of MM will only produce one of the options listed above at a time.)

127
Q

What is the most common cause of death in multiple myeloma?

128
Q

How does the bone marrow appear in multiple myeloma?

What is seen on peripheral smear?

A

Punched-out, lytic lesions;

roleaux formation

129
Q

In the attached image of multiple myeloma cells, what is the lighter shaded area of the cell adjacent to the nucleus (note: this is seen in several lymphomas)?

A

The enlarged Golgi apparati

(highlighted below)

130
Q

How is the M component of multiple myeloma measured and classified?

A

Serum protein electrophoresis

+

Immunofixation (e.g. checking gamma vs. lambda monoclonal production)

131
Q

In an asymptomatic patient, you identify that they have a proliferation of plasma cells in their bone marrow replacing < 10% of the bone marrow cellularity. Upon further investigation, you identify a small M spike (<3 g/dL) .

What is the diagnosis?

A

Monoclonal gammopathy of undetermined significance

(MGUS)

132
Q

How often does monoclonal gammopathy of undetermined significance progress to multiple myeloma?

A

Rarely

(typically follows benign course)

133
Q

What malignancy is strongly associated with EBV infection and the appearance in this micrograph?

(Clear vacuoles within leukocytes in peripheral smear)

A

Burkitt lymphoma

(Burkitt has bubbles)

T1 - Phase 2 - Systems Modules (I) (27 decks)

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