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Pathology Exam 2 > Lecture 16 - WBC Disorders > Flashcards

Lecture 16 - WBC Disorders Flashcards

1
Q

What are malignant proliferations of cells native to lymphoid tissue - lymphocytes and their precursors and derivatives?

A

lymphomas

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2
Q

Lymphoma tumors usually arise in lymphoid tissue and can spread to invovle what other areas?

A
  • solid tissue
  • marrow
  • blood
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3
Q

What are the two main types lymphomas are categorized into?

A

Hodgkin and non-Hodgkin lymphomas

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4
Q

what are malignant proliferations of cells native to the bone marrow, which often spillover into the blood?

A

Leukemias

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5
Q

leukemias can spread to involve solid organs, specifically which two?

A

liver and spleen

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6
Q

This distinction between lymphoma and the lymphocytic leukemias can be difficult sometimes, since in advanced states both can involve what?

A

both can involve lymphoid tissue at any site

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7
Q

what type of lymphoma has the characteristic morphologically of the presence of Reed-Sternberg cells admixed with variable inflammatory infiltrate?

A

hodgkin lymphoma

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8
Q

Is non-hodgkin lymphoma or hodgkin lymphoma accompanied by a fever?

A

hodgkin lymphoma is often accompanied by fever

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9
Q

Is non-HL or HL accompanied as arising in a single lymph node or chain of nodes?

A

Hodgkin lymphoma is accompanied as arising in a single lymph node or chain of nodes

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10
Q

Is HL more common in younger or older individuals and what is the averae age?

A

HL more common in young adults and the average age is 30 years

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11
Q

specifically why is staging so important in Hodgkin lymphoma?

A

because it is characterized by contiguous spread within lymph node groups

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12
Q

the cause of Hodgkin lymphoma is unknown, but what has been implicated in playing a role?

A

EBV (epstein barr virus)

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13
Q

what is the neoplastic cell associated with Hodgkin’s lymphoma?

A

Reed-Sternberg (RS) cell

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14
Q

Describe a Reed-Sternberg (RS) cell

A

A distinctive large cell with mirror image nuclei and prominent nucleoli

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15
Q

In HL are there usually small or large numbers of RS cells present in the involved node?

A

usually only SMALL numbers are present in the involved node

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16
Q

A diagnosis of Hodgkin lymphoma requires the presence of what?

A

RS cells in the appropriate histologic background: RS-like cells alone are NOT specific, and may be seen in non-neoplastic disorders like infectious mononucleosis

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17
Q

Where may RS cells arise?

A

RS cells may arise from specialized antigen-presenting cells in lymph nodes; the precise origin of the RS cell remains uncertain
*EBV genome can be identified in the RS cells in some cases

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18
Q

what does staging refer to?

A

the assessment of the amount of tumor burden and its distribution in the body

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19
Q

what does it mean to have low stage disease?

A

low stage disease denotes localized lymph node involvement, without systemic signs (fever weight loss) and has a better prognosis

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20
Q

what does it mean to have high stage disease?

A

Widespread disease, often with bone marrow involvement, has a worse prognosis
*More aggressive forms of disease typically present in higher stages

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21
Q

The choice of therapy (chemotherapy, radiotherapy, or both) and prognosis are based on what?

A

stage

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22
Q

What is the main treatment for HL and what treatment is used less today

A

chemotherapy is the main treatment and to a less extent radiotherapy

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23
Q

The stages of HL are further divided on the basis of absence or presence of systemic symptoms such as what?

A
  • fever, night sweats, significant unexplained weight loss

* Example: stage IIIA

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24
Q

Most patients typically have what as the initial manifestation of disease in Hodgkin’s lymphoma?

A

-enlarged painless superficial lymph node involvement

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25
Q

involvement of other lymph nodes in the chest and abdomen can occur, but is less common at presentation, except in what type of HL?

A

lymphocyte-depleted type

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26
Q

Involvement of what two organs increase the stage?

A

spleen and liver

*Are assessed by MRI

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27
Q

What complications can occur in advanced disease of HL?

A
  • infections (decrease cell-mediated immunity)
  • anemia
  • thrombocytopenia
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28
Q

what therapy has dramatically improved the survival in HD?

A

combination chemotherapy and to a lesser extent radiotherapy

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29
Q

There is a low, but definite risk for developing acute leukemia after treatment with chemotherapy and radiotherapy because of what?

A

bone marrow toxicites of the chemotherapeutic drugs used

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30
Q

where does Non-Hodgkin lymphomas (NHL) arise and where can it spread

A

arise in lymphoid tissue - either in lymph nodes or lymphoid tissue of solid organs - have the capacity to spread into other nodes, solid organs, bone marrow and blood

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31
Q

does NHL of HL have more morphologic diversity?

A

more morphologic diversity in NHL

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32
Q

How many different subtypes of NHL are recognized for purposes of determining prognosis and selecting therapy?

A

more than two dozen subtypes

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33
Q

How many subtypes comprise over 90% of the NHLs in the US?

A

only 8 of these subtypes

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34
Q

Do NHLs tend to have multiple or isolated node involvement?

A

NHLs tend to have multiple node involvement, more frequent extanodal spread and peripheral blood involvemnt

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35
Q

(T/F) NHL affects mostly young individuals

A

FALSE

NHL affect all ages

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36
Q

Similar to HD what is required for diagnosis of NHL?

A

histologic examination of involved tissue

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37
Q

what percent of NHL are clonal neoplasms of B lymphocytes?

A

majority (85%) of NHL are clonal neoplasms of B lymphocytes

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38
Q

B lymphocytes are specialized for what?

A

antibody production

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39
Q

what percent of NHL are of T cell origin?

A

15% - the remainder of NHL is of T cell origin

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40
Q

B lymphocytes normally have to capacity to differentiate into what as part of the immune response, just as T-lymphocytes become activated as part of the normal immune response?

A

plasma cells (the most mature B cell)

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41
Q

when does a lymphoma develop

A

when there is monoclonal expansion of lymphocytes that have been “arrested” (or have acquired a genetic rearrangement that alters growth regulation) at a particular stage in transformation

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42
Q

(T/F) the clonal cells proliferate with normal regulatory mechanisms

A

FALSE

The clonal cells proliferate WITHOUT normal regulatory mechanisms

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43
Q

All lymphoid neoplasms are considered to arise from what?

A

a single transformed cell

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44
Q

Daughter cells synthesize antigen receptor proteins identical to the original cell that reflect a “frozen” state of what?

A

B cell maturation

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45
Q

NHL is a tumor of the immune system, do immune abnormalities occur frequently or infrequently?

A

immune abnormalities occur frequently

hypogammaglobulnemia - increased risk of infection

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46
Q

What is the classification of NHL?

A

moderately complicated

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47
Q

What is the principal reason for the classification system?

A

to facilitate communication and to obtain information on response to treatment and prognosis in similar histologic types

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48
Q

NHLs are classified on the basis of what four things?

A
  1. Morphology (microscopic appearance)
  2. Cell or origin (immunophenotype)
  3. Clinical features
  4. Genotype
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49
Q

What organization convenes panels of lymphoma experts to examine the accuracy and utility of the classification system

A

World health organization

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50
Q

T/F: There is less correlation between stage and prognosis in NHL than in HD

A

True

*Cell type and tumor proliferative index are better correlated with prognosis

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51
Q

Describe stage 1 distribution of disease

A

involves single lymph node region or extralyphatic organ or site

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52
Q

Describe stage 2 distribution of disease

A

involves two or more lymph node regions on side same of diaphragm along or with involvement of contiguous extrapyramidal organ or tissue

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53
Q

Describe stage 3 distribution of disease

A

Involves lymph node regions on both sides of diaphragm which may include spleen

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54
Q

Describe stage 4 distribution of disease

A

Multiple or disseminated foci of involvement of one or more extralymphatic organs or tissue with or without lymphatic involvement

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55
Q

in NHL is the clinical presentation painful or painless

A

usually painless

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56
Q

What area of the body is often enlarged with NHL and what two organs does it often spread?

A

enlarged lymph nodes, evidence of extranodal spread - enlarged liver or spleen

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57
Q

is more marrow involvement more common in HL of NHL

A

NHL

*And lymphoma cells may circulate in peripheral blood

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58
Q

Circulating lymphoma cells in the peripheral blood represent what phase of disease?

A

‘leukemic phase’ of the disease, in distinction to the group of diseases classified as leukemias

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59
Q

NHL can spread to involve solid organs, GI tract, bones, and what other system?

A

Nervous system

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60
Q

In NHL enlargement of lymph node groups can produce obstruction where?

A

can produce vascular and lymphatic obstruction

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61
Q

(T/F) in NHL complications with infections, anemia, and thrombocytopenia occur.

A

true

62
Q

what is the treatment for NHL?

A

chemotherapy and less often radiotherapy

63
Q

What treatment can be used for highly resistant disease, allowed higher doses of chemotherapy to be delivered with the hope of a cure?

A

bone marrow transplant

64
Q

What is leukemia?

A

Malignant neoplasms of hematopoietic tissue that arise in the bone marrow

  • The malignant cells proliferate in the bone marrow, commonly producing a pattern of diffuse infiltration
  • There is often “spill over” of the proliferating cells into the blood and other groups
65
Q

The cell types of acute and chronic leukemias include what?

A

myelogenous (myeloid and monocytic) and lymphoid

66
Q

What are the basic classification of leukemias (4 of them)

A

Acute lymphoblastic leukemia (ALL)
Chronic lymphhocytic leukemia (CLL)
Acute myelogenous leukemia (AML)
Chronic myelogenous leukemia (CML)

67
Q

Is acute of chronic leukemia described: indolent, often long survival; survival in years

A

chronic leukemia

68
Q

Is acute or chronic leukemia described: rapid, usually fatal, survival in months

A

acute leukemia

69
Q

Is acute or chronic leukemia described: in the peripheral blood mostly blasts (immature cells)

A

acute leukemia

70
Q

Is acute or chronic leukemia described: in the peripheral blood mostly mature cells

A

chronic leukemia

71
Q

Is acute or chronic leukemia described: White cell count often increased

A

both acute and chronic leukemia - but acute leukemia is decreased in 30%

72
Q

Is acute or chronic leukemia described: more than 20% blasts in the bone marrow

A

acute leukemia

73
Q

Is acute or chronic leukemia described: blasts usually not increased in the bone marrow

A

chronic leukemia

74
Q

In acute lymphoblastic leukemia (ALL) the proliferating cell is what?

A

A primitive lymphoid cell

75
Q

Which type of leukemia accounts for 40% of the acute leukemias and is the most frequent type in children less than 15 years old

A

acute lymphoblastis leukemia (ALL)

76
Q

which type of leukemia is the principal cause of cancer deaths in childhood, with peak incidence at age 4, but can affect persons of all ages?

A

acute lymphoblastic leukemia (ALL)

77
Q

what are the four subtypes that are recognized immunologically in acute lymphoblastic leukemia (ALL)?

A
  1. early B precursor
  2. Pre-B
  3. Mature B
  4. T cell
78
Q

cytogenetic analysis has prognostic significance and what is the subtype with the best prognosis (most are children)

A

hyperdiploidy ( more than 50 chromosomes per leukemic cell)

79
Q

in enlargement of lymph nodes, liver and spleen more common in AML or ALL?

A

enlargemnt of lymphnodes, liver and spleen is more common in ALL
*ALL also often involves the central nervous system

80
Q

what is the best prognosis group for acute lymphatic leukemia (ALL)?

A

children aged 2-10 with pre-B cell type

81
Q

What is the proliferating cell in acute myelogenous leukemias (AML)?

A

primitive myeloid cell

82
Q

what is the cytoplasmic evidence of myeloid differentiation in acute myelogenous leukemia (AML)?

A

includes the presence of several types of granules (myeloperoxidase) found in more mature myeloid cells

83
Q

What are Auer rods in acute myelogenous leukemia (AML)?

A

cytoplasmic inclusions that when present are diagnostic

84
Q

How can many subtypes of AML be recognized?

A

Based on morphology, cytochemistry, immunophenotype and karyotype
*KARYOTYPE IS MOST PREDICTIVE OF PROGNOSIS

85
Q

AML affects what population and what is the median age?

A

usually affects an older adult population, with a median age of 50 years

86
Q

What is granulocytic sarcoma?

A

in AML sometimes the lesional cells will proliferate in soft tissue (including the gingivae)

87
Q

what is the current therapy for AML undergoing evaluation/ trial for treatment of refractory patient as well as those in first remission from standard chemotherapy, as is a potentially curative procedure?

A

Bone marrow transplant

88
Q

What is the proliferating cell in chronic lymphocytic leukemia (CLL)?

A

the proliferating cell is a mature-appearing, but immunologically incompetent, lymphocyte
*Immunologically these cells can be proven to be monoclonal (derived from the same precursor cell) and within a given patient all have identical cell surface phenotype

89
Q

In CLL what percentage are B cell type?

A

more than 95%

90
Q

In CLL what immunoglobulin is commonly expressed?

A

IgM kappa surface immunoglobulin

91
Q

Chronic Lymphocytic Leukemia (CLL) accounts for what percent of chronic leukemias and is most common in adults older than what age?

A

2/3 or 66% of chronic leukemias and is most common in adults over 60

92
Q

what is the male: female ratio in CLL?

A

2:1

93
Q

In CLL is the course of the disease is indolent, and patients may not require treatment when?

A

they may not require treatment in the early stages

94
Q

In CLL as the monoclonal lymphocytes proliferate and migrate to other lymphoid sites there can be involvement of ____, _____, and ____ _____

A

spleen, liver and lymph nodes

95
Q

In CLL, Peripheral leukocytosis is common and can be how many time normal?

A

5-10X normal

96
Q

In CLL, as the marrow is overrun by leukemic cell eventually what may develop?

A

cytopenias (anemia and thrombocytopenia)

97
Q

In CLL, because the neoplastic lymphocytes do not respond to antigenic stimuli, what develops in most patients?

A

hypogammagobulinemia

98
Q

What is the median survival for chronic lymphocytic leukemia (CLL)

A

4-6 years

99
Q

What is the proliferating cell in chronic myelogenous leukemia (CML)?

A

an immature hematopoietic cell, a stem cell from which all other hematopoietic cells arise

100
Q

In CML the stem cell pool is increased how many time normal?

A

10-20 X normal, and although the cell can mature, there is failure to respond to normal regulators of growth

101
Q

In CML, there is a marked increase in peripheral white cell count, with all myeloid ell types present especially which ones?

A

myelocytes, eosinophils, and basophils

102
Q

what is the specific chromosomal abnormality is found in chronic myelogenous leukemia (CML) that occurs in all the proliferating cells?

A

Philadelphia chromosome [t(9;22)]

103
Q

The chromosomal abnormality results in fusion of what genes, which mimic the effects of growth factor activation, driving the proliferation of CML

A

BCR-ABL genes

*While this fusion gene is ALWAYS present in CML, it is not unique to this disorder

104
Q

what percent of chronic leukemias does CML account for and what the the age range for the adults it effects?

A

1/3 of chronic leukemia

adults from 25-60 years of age

105
Q

In CML, enlargement of what organ to the due to proliferation of abnormal cells is almost always present?

A

the spleen

106
Q

the terminal phase of CML is also known as what and characterized by what?

A

Blast crisis

marked by relative increase in immature cells in peripheral blood and bone marrow, and decreased response to treatment

107
Q

the terminal phase of CML is equivalent to an acute leukemia, and is what fraction of myeloid linage and what fraction of lymphoid lineage?

A

myeloid lineage (2/3) and lymphoid lineage (1/3)

108
Q

what is the initial therapy of CML?

A

targeted inhibitors of the BCR-ABL tyrosine kinase, which induce complete remission in a high percentage of patients
*With relapsed or resistant disease, bone marrow transplant may be performed, although this is risky in older patients

109
Q

In leukemia, the clinical features result from:

A
  1. impairment of marrow function as abnormal cells suppress growth of normal cells
  2. infiltration of body organs due to proliferation of the abnormal cells
110
Q

anemia is manifest as what three things?

A

pallor, weakness, and fatigue

111
Q

what is thrombocytopenia and what does it produce?

A

decreased platelets and it produces bleeding and bruises

112
Q

Why do infections result in leukemia?

A

infectiosn result from decreased production of mature granulocytes and production of non-functional granulocytes and/or lymphocytes

113
Q

in leukemia, what can result due to infection or increased metabolism of proliferating cells?

A

fever

114
Q

In leukemia, organ enlargement int he lymph nodes, spleen, and liver occurs because of what?

A

the abnormal cells proliferate in these sites

115
Q

In leukemia, abnormal pain or obstrauction of vascular and lymphatic channels can result. Infiltration of the gingiva is a feature commonly associated with which type of leukemia?

A

acute myelo-monocytic leukemias

116
Q

Plasma cell disorders result from what?

A

clonal expansion of immunoglobulin-secreting cells

117
Q

In plasma cell disorders, the secreted immunoglobulin (or portion of immunoglobulin) results in increases in serum monoclonal protein (M component) which may have adverse effects of what two functions?

A

renal and neurologic function

118
Q

what is the proliferating cell in multiple myeloma?

A

plasma cell that produces immunoglobulin

119
Q

In multiple myeloma, because this is a clonal disorder, only one immunoglobulin type is produced by the which cells and what immunoglobulin type is produced in most cases?

A 
neoplastic cells
* In 60% this is IgG
In 20-25% IgA
remainder it is only kappa or lamba light chain
Rarely is it IgM, IgD, or IgE

*In some patients complete monoclonal immunoglobulin is present as well as excess light chains

120
Q

what is Bence Jones proteinuria?

A

when only light chains are produced, patients can excrete the lower molecular weight light chains in the urine

121
Q

What characterizes myeloma?

A

multifocal destructive bone lesions

122
Q

Bone resorption results from secretion of _____ activating factors by the myeloma cells

A

osteoclast

123
Q

Proteinaceous casts may for in what part of the body

A

the kidneys (myeloma kidney)

124
Q

Hypercalcemia is often present and _______ may form from the monoclonal protein

A

amyloid

125
Q

how many cases of multiple myeloma are projected to be diagnosed in 2015 in the US, and what is the average age of the patient

A

24,000

average patient is 70 years old

126
Q

What do patients often present with in multiple myeloma?

A

bone pain, hypercalcemia, and renal disease

127
Q

As the tumor cells proliferate, complications with recurrent infections, anemia, and thrombocytopenia develop due to what?

A

destruction of normal marrow by the tumor

128
Q

What makes the diagnosis in multiple myeloma?

A

documenting monoclonal protein and skeletal lesions

129
Q

the terminal phase of CML is equivalent to an acute leukemia, and is what fraction of myeloid linage and what fraction of lymphoid lineage?

A

myeloid lineage (2/3) and lymphoid lineage (1/3)

130
Q

what is the initial therapy of CML?

A

targeted inhibitors of the BCR-ABL tyrosine kinase, which induce complete remission in a high percentage of patients
*With relapsed or resistant disease, bone marrow transplant may be performed, although this is risky in older patients

131
Q

In leukemia, the clinical features result from:

A
  1. impairment of marrow function as abnormal cells suppress growth of normal cells
  2. infiltration of body organs due to proliferation of the abnormal cells
132
Q

anemia is manifest as what three things?

A

pallor, weakness, and fatigue

133
Q

what is thrombocytopenia and what does it produce?

A

decreased platelets and it produces bleeding and bruises

134
Q

Why do infections result in leukemia?

A

infectiosn result from decreased production of mature granulocytes and production of non-functional granulocytes and/or lymphocytes

135
Q

in leukemia, what can result due to infection or increased metabolism of proliferating cells?

A

fever

136
Q

In leukemia, organ enlargement int he lymph nodes, spleen, and liver occurs because of what?

A

the abnormal cells proliferate in these sites

137
Q

In leukemia, abnormal pain or obstrauction of vascular and lymphatic channels can result. Infiltration of the gingiva is a feature commonly associated with which type of leukemia?

A

acute myelo-monocytic leukemias

138
Q

Plasma cell disorders result from what?

A

clonal expansion of immunoglobulin-secreting cells

139
Q

In plasma cell disorders, the secreted immunoglobulin (or portion of immunoglobulin) results in increases in serum monoclonal protein (M component) which may have adverse effects of what two functions?

A

renal and neurologic function

140
Q

what is the proliferating cell in multiple myeloma?

A

plasma cell that produces immunoglobulin

141
Q

In multiple myeloma, because this is a clonal disorder, only one immunoglobulin type is produced by the which cells and what immunoglobulin type is produced in most cases?

A 
neoplastic cells
* In 60% this is IgG
In 20-25% IgA
remainder it is only kappa or lamba light chain
Rarely is it IgM, IgD, or IgE

*In some patients complete monoclonal immunoglobulin is present as well as excess light chains

142
Q

what is Bence Jones proteinuria?

A

when only light chains are produced, patients can excrete the lower molecular weight light chains in the urine

143
Q

What characterizes myeloma?

A

multifocal destructive bone lesions

144
Q

Bone resorption results from secretion of _____ activating factors by the myeloma cells

A

osteoclast

145
Q

Proteinaceous casts may for in what part of the body

A

the kidneys (myeloma kidney)

146
Q

Hypercalcemia is often present and _______ may form from the monoclonal protein

A

amyloid

147
Q

how many cases of multiple myeloma are projected to be diagnosed in 2015 in the US, and what is the average age of the patient

A

24,000

average patient is 70 years old

148
Q

What do patients often present with in multiple myeloma?

A

bone pain, hypercalcemia, and renal disease

149
Q

As the tumor cells proliferate, complications with recurrent infections, anemia, and thrombocytopenia develop due to what?

A

destruction of normal marrow by the tumor

150
Q

What makes the diagnosis in multiple myeloma?

A

documenting monoclonal protein and skeletal lesions

Pathology Exam 2 (8 decks)

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