CH6 - White Blood Cell Disorders Flashcards

1
Q

What does hematopoetic CD34+ stem cells produce?

A

Myeloid stem cells and lymphoid stem cells

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

What does myeloid stem cells produce?

A

Erythroblast, Myeloblast, Monoblast, Megakaryoblast

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

What does erythroblast produce?

A

RBCs

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

What does myeloblast produce?

A

Neutrophils, basophils, Eosinophils

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

What does monoblast produce?

A

Monocytes

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

What does megakaryoblast produce?

A

megakaryocytes

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

What does lymphoid stem cells produce?

A

B lymphoblast and T Lymphoblast

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

What does B lymphoblast produce?

A

Naïve Bcells

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

What does Naïve B cells produce?

A

Plasma cells

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

What does T lymphoblast produce?

A

Naïve Tcells

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

What does Naïve T cells produce?

A

CD8+ and CD4+ T cells

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

How does hematopoiesis occur?

A

via a stepwise maturation of CD34+ hematopoietic stem cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What happens to hematopoetic stem cells?

A

Cells mature and are released from the bone marrow into the blood.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the normal white blood cell (WBC) count?

A

it is approximately 5-10 K/pL

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

What is a low WBC count? What is it called?

A

(< 5 K) is called leukopenia.

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

What is a high WBC count? What is it called?

A

(> 10 K) is called leukocytosis.

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

What is a low or high WBC count usually due to?

A

a decrease or increase in one particular cell lineage.

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

What is neutropenia?

A

refers to a decreased number of circulating neutrophils

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

What are some of the causes of neutropenia?

A

1) Drug toxicity 2) severe infection

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

How can drug toxicity lead to neutropenia?

A

e.g., chemotherapy with alkylating agents, cause damage to stem cells resulting in decreased production of WBCs, especially neutrophils.

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

How does severe infection lead to neutropenia?

A

e.g., gram-negative sepsis leads to increased movement of neutrophils into tissues resulting in decreased circulating neutrophils.

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

What is GM-CSF or G-CSF?

A

granulocyte monocyte stimulating factor or granulocyte stimulating factor, it can be used to boost the neutrophil count decreasing the risk of infection

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

What is lymphopenia?

A

it refers to a decreased number of circulating lymphocytes

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

What are the some of the causes of lymphopenia?

A

1) immunodeficiency 2) high cortisol state 3) autoimmune destruction 4) whole body radiation

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

What are some examples of immunodeficiency that lead to lymphopenia?

A

e.g., DiGeorge syndrome or HIV

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

How does a High Cortisol state lead to lymphopenia?

A

exogenous corticosteroids or Cushing syndrome, induces apoptosis of lymphocytes

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

What is an example of autoimmune destruction leading to lymphopenia?

A

e.g., systemic lupus erythematosus

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

How can whole body radiation lead to lymphopenia?

A

Lymphocytes are highly sensitive to radiation; lymphopenia is the earliest change to emerge after whole body radiation

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

What are the different types of leukocytosis?

A

1) neutrophilic leukocytosis 2) monocytosis 3) Eosinophilia 4) Basophilia 5) Lymphocytic leukocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What does neutrophilic leukocytosis refer to?

A

increased circulating neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the causes of neutrophilic leukocytosis?

A

1) Bacterial infection 2) tissue necrosis 3) High cortisol state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How does Bacterial infection or tissue necrosis lead to neutrophilic leukocytosis?

A

It induces release of marginated pool and bone marrow neutrophils, including immature forms (left shift)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

When immature cells are released into the blood, how are they characterized?

A

by decreased Fc receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is the marker for the decreased Fc receptor?

A

CD16

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Why are Fc receptors important?

A

They help the neutrophil to recognize immunoglobulin which is going to act as an opsonin for phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

How does high cortisol state lead to neutrophilic leukocytosis?

A

impairs leukocyte adhesion, leading to release of marginated pool of neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What does monocytosis refer to?

A

increased circulating monocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What are the causes of monocytosis?

A

inflammatory states (e.g., autoimmune and infections) and malignancy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What does eosinophilia refer to?

A

increased circulating eosinophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are the causes of eosinophilia?

A

include allergic reactions (type I hypersensitivity), parasitic infections, and Hodgkin lymphoma,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is eosinophilia driven by?

A

increased eosinophil chemotactic factor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What does basophilia refer to?

A

increased circulating basophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What is basophilia classically seen in?

A

chronic myeloid leukemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What does lymphocytic leukocytosis refer to?

A

increased circulating lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What are the causes of lymphocytic leukocytosis?

A

1) viral infection 2) Bordetella pertussis infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

How does viral infections lead to lymphocytic leukocytosis?

A

T lymphocytes undergo hyperplasia in response to virally infected cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How does Bordetella pertussis infection lead to lymphocytic leukocytosis?

A

Bacteria produce lymphocytosis-promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph node.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is infectious mononucleosis?

A

EBV infection that results in a lymphocytic leukocytosis comprised of reactive CD8+ T cells; CMV is a less common cause

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

How is EBV transmitted?

A

by saliva (kissing disease); classically affects teenagers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What does EBV primarily infect?

A
  1. Oropharynx, resulting in pharyngitis 2. Liver, resulting in hepatitis with hepatomegaly and elevated liver enzymes 3. B cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

CD8+ T-cell response leads to what?

A

1) LAD 2) Splenomegaly 3) High WBC count with atypical lymphocytes (reactive CD8+ T cells) in the blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

How does the CD8+ T cell response lead to generalized lymphadenopathy (LAD)?

A

It is due to T-cell hyperplasia in the lymph node paracortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

How does CD8+ T cell response lead to splenomegaly?

A

It is due to T-cell hyperplasia in the periarterial lymphatic sheath (PALS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What is used for screening of IM?

A

The monospot test

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What does the monospot test do?

A

Detects IgM antibodies that cross-react with horse sheep red blood cells (heterophile antibodies)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

When would the monospot test turn positive?

A

Usually turns positive within 1 week after infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What would a negative monospot test suggest?

A

CMV as a possible cause of IM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

How is a definitive diagnosis for IM made?

A

by serologic testing for the EBV viral capsid antigen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What are the complications of EBV?

A

1) increased risk for splenic rupture 2) Rash 3) Recurrence and B cell lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What are patients told who have an increased risk for splenic rupture?

A

patients are generally advised to avoid contact sports for one year.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

When might a rash develop as a complication of EBV?

A

if exposed to ampicillin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

With EBV complications, why is there a risk of recurrence and B cell lymphoma?

A

Dormancy of virus in B cells leads to increased risk for both recurrence and B-cell lymphoma, especially if immunodeficiency (e.g., HIV) develops.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What is acute leukemia?

A

Neoplastic proliferation of blasts; defined as the accumulation of >20% blasts in the bone marrow.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What is the acute presentation for acute leukemia?

A

Anemia (fatigue), thrombocytopenia (bleeding), or neutropenia (infection)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What is the reason for the acute presentation of acute leukemia?

A

Increased blasts crowd-out normal hematopoiesis,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

In acute leukemia, why is there a high WBC count?

A

Blasts usually enter the blood stream, resulting in a high WBC count

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Describe blasts.

A

they are large, immature cells, often with punched out nucleoli

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What is acute leukemia subdivided into?

A

acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

The subdivision of acute leukemia is based on what?

A

the phenotype of the blasts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What is acute lymphoblastic leukemia?

A

Neoplastic accumulation of lymphoblasts (> 20%) in the bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Why is TdT useful in characterizing lymphoblasts?

A

It is absent in myeloid blasts and mature lymphocytes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Acute lymphoblastic leukemia most commonly arises in whom?

A

children

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

What is acute lymphoblastic leukemia associated with and when does it usually arise?

A

Down syndrome (usually arises after the age of 5 years)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Acute lymphoblastic leukemia is subclassified into? What is it based on?

A

B-ALL and T-ALL based on surface markers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

What is the most common type of ALL?

A

B-ALL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What is B-ALL usually characterized by?

A

lymphoblasts (TdT+) that express CD10, CD19, and CD20.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What is the treatment for B-ALL?

A

Excellent response to chemotherapy; requires prophylaxis to scrotum and CSf

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What is the prognosis B-ALL based on?

A

It is based on cytogenetic abnormalities,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Which B-ALL has a good prognosis and is more commonly seen in children?

A

t(12;21)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Which B-ALL has a poor prognosis and in what population is it seen?

A

t(9;22) has a poor prognosis; more commonly seen in adults (Philadelphia+ALL)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What is T-ALL characterized by?

A

lymphoblasts (TdT+) that express markers ranging from CD2 to CDH (e.g., CD3, CD4, CD7). The blasts do not express CD10.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

How does T-ALL usually present?

A

Usually presents in teenagers as a mediastinal (thymic) mass (called acute lymphoblastic lymphoma because the malignant cells form a mass)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

What is acute myeloid leukemia?

A

Neoplastic accumulation of myeloblasts (> 20%) in the bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

How are myeloblasts usually characterized?

A

by positive cytoplasmic staining for myeloperoxidase (MPO)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What may be seen in the characterization of myeloblasts?

A

Crystal aggregates of MPO may be seen as Auer rods

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

In whom does acute myeloid leukemia most commonly arise?

A

older adults (average age is 50-60 years)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

What is the subclassification of AML based on?

A

cytogenetic abnormalities, lineage of myeloblasts, and surface markers.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

What are the high-yield subtypes?

A

Acute promyelocytic leukemia, Acute monocytic leukemia and acute megakaryoblastic leukemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

What is acute promyelocytic leukemia characterized by?

A

t(15;17), which involves translocation of the retinoic acid receptor (RAR) on chromosome 17 to chromosome 15

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What is the effect of RAR disruption?

A

It blocks maturation and promyelocytes (blasts) accumulate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

How does acute promyelocytic leukemia lead to increased risk for DIC?

A

Abnormal promyelocytes contain numerous primary granules that increase the risk for DIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

What is the treatment for acute promyelocytic leukemia?

A

with all-trans retinoic acid (ATRA, a vitamin A derivative)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

How does ATRA work?

A

It binds the altered receptor and causes the blasts to mature (and eventually die)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

What is acute monocytic leukemia?

A

Proliferation of monoblasts; usually lack MPO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

In acute monocytic leukemia what do blasts characteristically do?

A

infiltrate gums

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

What is acute megakaryoblastic leukemia?

A

Proliferation of megakaryoblasts; lack MPO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

What is acute monocytic leukemia associated with?

A

Down syndrome (usually arises before the age of 5)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

What is myelodysplastic syndrome?

A

acute myeloid leukemia may also arise from pre-existing dysplasia = myelodysplastic syndromes, especially with prior exposure to alkylating agents or radiotherapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

What do myelodysplastic syndromes usually present with?

A

cytopenias, hypercellular bone marrow, abnormal maturation of cells, and increased blasts < 20%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

With myelodysplastic syndromes resulting in acute myeloid dysplastic syndrome what do most patients die from?

A

Most patients die from infection or bleeding, though some progress to acute leukemia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

What is chronic leukemia?

A

Neoplastic proliferation of mature circulating lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

What is chronic leukemia characterized by?

A

a high WBC count

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

Describe the onset of chronic leukemia?

A

Usually insidious in onset and seen in older adults

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

What is chronic lymphocytic leukemia?

A

Neoplastic proliferation of naive B cells that co-express CD5 and CD20;

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

What is the most common leukemia overall?

A

Chronic lymphocytic leukemia (CLL)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

In CLL what is seen on the blood smear?

A

Increased lymphocytes and smudge cells are seen on blood smear

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

small lymphocytic lymphoma

A

In CLL, with involvement of lymph nodes leads to generalized lymphadenopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

What are the complications of CLL?

A

1) Hypogammaglobulinemia, 2) autoimmune hemolytic anemia, 3) Richter transformation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

What is the most common of death in CLL?

A

infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

What is Richter transformation?

A

transformation to diffuse large B-cell lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

What is Richter transformation marked clinically by?

A

an enlarging lymph node or spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

What is Hairy cell leukemia?

A

Neoplastic proliferation of mature B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

What characterizes hairy cell leukemia?

A

hairy cytoplasmic processes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

What are hairy cell leukemia cells positive for?

A

tartrate-resistant acid phosphatase (TRAP).

115
Q

What are the clinical features for hairy cell leukemia?

A

Splenomegaly, dry tap on bone marrow aspiration

116
Q

Why is there splenomegaly in hairy cell leukemia?

A

Due to accumulation of hairy cells in red pulp

117
Q

Why is there a dry tap on bone marrow aspiration in hairy cell leukemia?

A

due to marrow fibrosis

118
Q

How is lymphadenopathy related to hair cell leukemia?

A

Lymphadenopathy is usually absent

119
Q

What drug is used in the treatment of hairy cell leukemia?

A

2-CDA (cladribine)

120
Q

How does hair cell leukemia respond to cladribine?

A

excellent response

121
Q

How does cladribine work?

A

Its an adenosine deaminase inhibitor, adenosine accumulates to toxic levels in neoplastic B cells.

122
Q

What is adult T cell leukemia?

A

Neoplastic proliferation of mature CD4+ T cells (ATLL)

123
Q

What is adult T cell leukemia associated with?

A

Associated with HTLV-I (human T cell lymphotrophic virus -1)

124
Q

Where is ATLL associated with HTLV-1 most commonly seen in?

A

Japan and the Caribbean

125
Q

What are the clinical features for ATLL?

A

include rash (skin infiltration), generalized lymphadenopathy with hepatosplenomegaly, and lytic (punched-out) bone lesions with hypercalcemia

126
Q

What is mycosis fungoides?

A

Neoplastic proliferation of mature CD44 T cells that infiltrate the skin, producing localized skin rash, plaques, and nodules

127
Q

What are Patitrier microabscesses?

A

Aggregates of neoplastic cells in the epidermis

128
Q

Sezary syndrome

A

cells can spread to involve the blood, producing Sezary syndrome.

129
Q

What are Sezary cells?

A

Characteristic lymphocytes with cerebri form nuclei

130
Q

What would you see on blood smear in mycosis fungoides?

A

Sezary cells

131
Q

What are myeloproliferative disorders?

A

Neoplastic proliferation of mature cells of myeloid lineage; disease of late adulthood (average age is 50-60 years)

132
Q

What does myeloproliferative disorders result in?

A

high WBC count with hypercellular bone marrow

133
Q

How are myeloproliferative disorders characterized?

A

Cells of all myeloid lineages are increased; classified based on the dominant myeloid cell produced

134
Q

What are the complications for myeloproliferative disorders?

A

1) Increased risk for hyperuricemia and gout due to high turnover of cells 2) Progression to marrow fibrosis or transformation to acute leukemia

135
Q

What is chronic myeloid leukemia?

A

Neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors;

136
Q

In chronic myeloid leukemia what are characteristically increased?

A

basophils

137
Q

What is chronic myeloid leukemia driven by?

A

driven by t(9:22) - Philadelphia chromosome - which generates a BCR-ABL fusion protein with increased tyrosine kinase activity

138
Q

What is the first line treatment for chronic myeloid leukemia?

A

imatinib,

139
Q

What does imatinib do?

A

It blocks tyrosine kinase activity

140
Q

How is splenomegaly related to chronic myeloid leukemia?

A

Splenomegaly is common, enlarging spleen suggests accelerated phase of disease;

141
Q

In chronic myeloid leukemia what usually follows after splenomegaly?

A

transformation to acute leukemia

142
Q

What can chronic myeloid leukemia transform to?

A

AML in 2/3 of cases or ALL in 1/3 of cases since mutation is in a pluripotent stem cell,

143
Q

What is a leukemoid reaction?

A

Reactive neutrophilic leukocytosis

144
Q

How is CML distinguished from a leukemoid reaction (reactive neutrophilic leukocytosis)?

A

Negative LAP stain, inc basophils, t(9;22)

145
Q

What is a LAP stain?

A

leukocyte alkaline phosphatase (LAP) stain

146
Q

How is a LAP stain related to a leukemoid reaction?

A

granulocytes in a leukemoid reaction are LAP positive

147
Q

Why are basophils useful in determining the difference between a leukemoid reaction and CML?

A

Basophils are increased in CML and are absent with a leukemoid reaction

148
Q

How is t(9;22) useful in determining the difference between a leukemoid reaction and CML?

A

It is present in CML and absent in leukemoid reaction

149
Q

What is polycythemia vera?

A

Neoplastic proliferation of mature myeloid cells, especially RBCs

150
Q

In polycythemia vera, in addition to the RBC increase what are also increased?

A

Granulocytes and platelets are also increased

151
Q

What mutation is associated with polycythemia vera?

A

JAK2 kinase mutation

152
Q

What are the clinical symptoms for polycythemia vera due to?

A

they are mostly due to hyperviscosity of blood

153
Q

What are the clinical symptoms for polycythemia vera?

A
  1. Blurry vision and headache 2. Increased risk of venous thrombosis (e.g., hepatic vein, portal vein, and dural sinus) 3. Flushed face due to congestion (plethora) 4. Itching, especially after bathing (due to histamine release from increased mast cells)
154
Q

What is plethora in relation to PV?

A

One of the clinical symptoms; flushed face due to congestion

155
Q

Why is there itching in PV?

A

Itching, especially after bathing due to histamine release from increased mast cells

156
Q

What is the treatment for PV?

A

phlebotomy;

157
Q

What is the second-line therapy for PV?

A

hydroxyurea.

158
Q

What happens to a patient with PV who goes intreated?

A

Without treatment, death usually occurs within one year.

159
Q

How can PV be distinguished from reactive polycythemia?

A
  1. In PV, erythropoietin (EPO) levels are decreased, and Sao, is normal. 2. In reactive polycythemia due to high altitude or lung disease, SaO2 is low, and EPO is increased. 3. In reactive polycythemia due to ectopic EPO production from renal cell carcinoma, EPO is high, and Sao2 is normal.
160
Q

What are the EPO and SaO2 levels in PV?

A

EPO is decreased and SaO2 is normal

161
Q

What are the EPO and SaO2 levels in reactive polycythemia due to high altitude or lung disease?

A

EPO is increased and SaO2 is low

162
Q

What are the EPO and SaO2 levels in reactive polycythemia due to renal cell carcinoma?

A

EPO is high, SaO2 is normal

163
Q

What is essential thrombocythemia?

A

Neoplastic proliferation of mature myeloid cells, especially platelets

164
Q

In ET, in addition to the platelets what else is increased?

A

RBCs and granulocytes are also increased.

165
Q

What is mutation is ET associated with?

A

JAK2 kinase mutation

166
Q

What do the symptoms of ET result from?

A

they are related to an increased risk of bleeding and/or thrombosis.

167
Q

What do the symptoms of ET rarely progresses to?

A

marrow fibrosis or acute leukemia

168
Q

In ET what is there no significant risk for?

A

hyperuricemia or gout

169
Q

What is myelofibrosis?

A

It is neoplastic proliferation of mature myeloid cells, especially megakaryocytes

170
Q

What mutation is associated with myelofibrosis?

A

JAK2 kinase mutation in 50% of cases

171
Q

In myelofibrosis, what causes marrow fibrosis?

A

Megakaryocytes produce excess platelet-derived growth factor (PDGF) causing marrow fibrosis

172
Q

What are the clinical features for myelofibrosis?

A

1) splenomegaly 2) leukoerythroblastic smear 3) Increased risk of infection, thrombosis, and bleeding

173
Q

In myelofibrosis what is splenomegaly due to?

A

extramedullary hematopoiesis

174
Q

In myelofibrosis what is the leukoerythroblastic smear?

A

It’s tear-drop RBCs, nucleated RBCs, and immature granulocytes

175
Q

What is lymphadenopathy (LAD)?

A

it refers to enlarged lymph nodes

176
Q

Painful LAD is usually seen in what?

A

lymph nodes that are draining a region of acute infection (acute lymphadenitis)

177
Q

Painless LAD can be seen with what?

A

chronic inflammation (chronic lymphadenitis), metastatic carcinoma, or lymphoma.

178
Q

In inflammation, lymph node enlargement is due to what?

A

hyperplasia of particular regions of the lymph node

179
Q

What is follicular hyperplasia seen with?

A

(B-cell region) rheumatoid arthritis and early stages of HIV infection, for example.

180
Q

What is paracortex hyperplasia seen with?

A

(T-cell region) viral infections (e.g., infectious mononucleosis).

181
Q

What is involved with hyperplasia of sinus histiocytes?

A

It is seen in lymph nodes that are draining a tissue with cancer.

182
Q

What is lymphoma?

A

Neoplastic proliferation of lymphoid cells that forms a mass; may arise in a lymph node or in extranodal tissue

183
Q

What is lymphoma divided into?

A

non-Hodgkin lymphoma (NHL 60%) and Hodgkin lymphoma (HL 40%)

184
Q

NHL further classified based on what?

A

cell type (e.g., B versus T), cell size, pattern of cell growth, expression of surface markers, and cytogenetic translocations, - small, intermediate and large B cells

185
Q

What are some examples of small B cells?

A

follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma (i.e.. CLL cells that involve tissue)

186
Q

What are some examples of intermediate-sized B cells

A

Burkitt lymphoma

187
Q

What are some examples of large B cells

A

diffuse large B-cell lymphoma

188
Q

What is the overall frequency for NHL?

A

60%

189
Q

What is the overall frequency for HL?

A

40%

190
Q

What are the malignant cells of NHL?

A

Lymphoid cells

191
Q

What are the malignant cells of HL?

A

Reed-Sternberg cells

192
Q

What is the composition of mass for NHL?

A

lymphoid cells

193
Q

What is the composition of mass of HL?

A

Predominantly reactive cells (inflammatory cells and fibrosis)

194
Q

How does NHL present clinically?

A

Painless lymphadenopathy, usually arises in late adulthood

195
Q

How does HL present clinically?

A

Painless lymphadenopathy occasionally with ‘B’ symptoms, usually arises in young adults

196
Q

What is the spread of NHL?

A

Diffuse: often extranodal

197
Q

What is the spread of HL?

A

Contiguous; rarely extra nodal

198
Q

Do you use staging in NHL?

A

Limited importance

199
Q

Do you use staging in HL?

A

Guides therapy; radiation is the mainstay of treatment.

200
Q

Is there a Leukemic phase in lymphoma?

A

Occurs in NHL but not in HL

201
Q

What is follicular lymphoma?

A

Neoplastic proliferation of small B cells (CD20+) that form follicle-like nodules

202
Q

How does follicular lymphoma present clinically?

A

in late adulthood with painless lymph adenopathy

203
Q

What is follicular lymphoma driven by?

A

t(14;18)

204
Q

How does t(14:18) result in follicular lymphoma?

A

BCL2 on chromosome 18 translocates to the Ig heavy chain locus on chromosome 14 this results in overexpression of Bcl2, which inhibits apoptosis

205
Q

What is the treatment for follicular lymphoma?

A

is reserved for patients who are symptomatic and involves low-dose chemotherapy or rituximab (anti-CD20 antibody).

206
Q

What does follicular lymphoma progress to and how does it present?

A

diffuse large B-cell lymphoma which is an important complication and presents as an enlarging lymph node

207
Q

How is follicular lymphoma distinguished from reactive follicular hyperplasia?

A

1) disruption of normal lymph node architecture (maintained in follicular hyperplasia) 2) Lack of tangible body macrophages in germinal centers (tangible body macrophages are present in follicular hyperplasia) 3) Bcl2 expression in follicles (not expressed in follicular hyperplasia) 4) Monoclonality (follicular hyperplasia is polyclonal)

208
Q

What is mantle cell lymphoma?

A

Neoplastic proliferation of small B cells (CD20+) that expands the mantle zone

209
Q

How does mantle cell lymphoma present clinically?

A

presents in late adulthood with painless lymph adenopathy

210
Q

What is mantle cell lymphoma driven by?

A

t(ll;14)

211
Q

How does t(11;14) result in mantle cell lymphoma?

A

1) Cydin D1 gene on chromosome 11 translocates to Ig heavy chain locus on chromosome 14. 2) Overexpression of cydin Dl promotes Gl/S transition in the cell cycle, facilitating neoplastic proliferation

212
Q

What is marginal zone lymphoma?

A

Neoplastic proliferation of small B cells (CD 20+) that expands the marginal zone

213
Q

What is marginal zone lymphoma associated with?

A

chronic inflammatory states such as Hashimoto thyroiditis, Sjogren syndrome, and H pylori gastritis

214
Q

What is the marginal zone formed by?

A

post-germinal center B cells.

215
Q

What is MALToma?

A

it is marginal zone lymphoma in mucosal sites.

216
Q

How might Gastric MALToma regress

A

with treatment of H Pylori,

217
Q

What is burkitt lymphoma?

A

Neoplastic proliferation of intermediate-sized B cells (CD20+);

218
Q

What is butkitt lymphoma associated with?

A

EBV

219
Q

How does burkitt lymphoma classically present?

A

as an extranodal mass in a child or young adult

220
Q

What is specific about the african form of burkitts lymphoma?

A

usually involves the jaw

221
Q

What does the sporadic form of Burkitts lymphoma usually involve?

A

the abdomen

222
Q

What is Burkitt lymphoma driven by?

A

Driven by translocations of c-myc (chromosome 8)

223
Q

What is the most common translocation for Burkitts lymphoma?

A

t(8;14) is most common,

224
Q

In Burkitts lymphoma what does t(8:14) result in?

A

translocation of c-myc to the Ig heavy chain locus on chromosome 14.

225
Q

What does overexpression of c-myc oncogene do?

A

promotes cell growth

226
Q

How is Burkitts lymphoma characterized?

A

by high mitotic index and ‘starry-sky’ appearance on microscopy

227
Q

What is diffuse large B-cell lymphoma?

A

Neoplastic proliferation of large B cells (CD20+) that grow diffusely in sheets

228
Q

What is the most common form of non-hodgkins lymphoma?

A

Diffuse large B-cell lymphoma

229
Q

Describe diffuse large B-Cell lymphoma clinically?

A

Clinically aggressive (high-grade)

230
Q

How does diffuse large B-cell lymphoma arise?

A

either sporadically or from transformation of a low-grade lymphoma (e.g., follicular lymphoma)

231
Q

How does diffuse large B-cell lymphoma present?

A

Presents in late adulthood as an enlarging lymph node or an extranodal mass

232
Q

What is Hodgkins Lymphoma?

A

Neoplastic proliferation of Reed-Slernberg (RS) cells,

233
Q

What are Reed-Slernberg cells?

A

large B cells with multilobed nuclei and prominent nucleoli (‘owl-eyed nuclei’);

234
Q

Hodgkins lymphoma is classically positive for what?

A

CD15 and CD30

235
Q

What do RS cells secrete?

A

cytokines.

236
Q

What are the symptoms for HL

A

Occasionally results in ‘B’ symptoms (fever, chills, and night sweats)

237
Q

In HL what do the RS cells attract?

A

reactive lymphocytes, plasma cells, macrophages, and eosinophils

238
Q

What may the RS cells in HL lead to?

A

fibrosis

239
Q

What makes up a bulk of the tumor and form the basis for classification of HL?

A

Reactive inflammatory cells

240
Q

What are the subtypes of reactive inflammatory cells in HL?

A

Include 1. Nodular sclerosis 2. Lymphocyte-rich 3. Mixed cellularity 4. Lymphocyte-depleted

241
Q

What is the most common subtype of HL?

A

Nodular sclerosis (70% of all cases),

242
Q

What is the classic presentation for nodular sclerosis?

A

it is an enlarging cervical or mediastinal lymph node in a young adult, usually female

243
Q

Dsecribe the lymph node in nodular sclerosis?

A

It is divided by bands of sclerosis; RS cells are present in lake-like spaces (lacunar cells),

244
Q

What are lacunar cells?

A

Lake like spaces in the lymph node where the RS cells are present

245
Q

What type of HL has the best prognosis of all types?

A

Lymphocyte-rich

246
Q

In HL mixed cellularity is often associated with what?

A

abundant eosinophils (RS cells produce IL-5).

247
Q

What is the most aggressive HL type and in whom is it usually seen?

A

Lymphocyte-depleted is the most aggressive of all types; usually seen in the elderly and HIV-positive individuals

248
Q

What are the plasma cell disorders?

A

Dyscrasias: 1) multiple myeloma 2) MGUS 3) Waldenstrom Macroglobulinemia

249
Q

What is multiple myeloma?

A

Malignant proliferation of plasma cells in the bone marrow

250
Q

Whis the most common primary malignancy of bone?

A

metastatic cancer,

251
Q

What is the most common malignant lesion of bone overall?

A

Multiple myeloma

252
Q

In multiple myeloma what is usually present?

A

High serum IL-6 is sometimes present; stimulates plasma cell growth and immunoglobulin production

253
Q

What are the clinical features for multiple myeloma?

A

1) Bone pain with hypercalcemia 2) Elevated serum protein 3) increased risk of infection 4) Rouleaux formation of RBC’s on blood smears 5) Primary AL amyloidosis 6) Proteinuria

254
Q

Why is there bone pain with hypercalcemia in multiple myeloma?

A

Neoplastic plasma cells activate the RANK receptor on osteoclasts, leading to bone destruction.

255
Q

With multiple myeloma what might you see on x-ray?

A

Lytic, ‘punched-out’ skeletal lesions are seen on x-ray, especially in the vertebrae and skull; increased risk for fracture

256
Q

Why is there elevated serum protein in multiple myeloma?

A

Neoplastic plasma cells produce immunoglobulin;

257
Q

In multiple myeloma, what is seen on electrophoresis?

A

M spike is present on serum protein electrophoresis (SPEP), most commonly due to monoclonal IgG or IgA

258
Q

In multiple myeloma why is there increased risk of infection?

A

Monoclonal antibody lacks antigenic diversity

259
Q

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

A

infection

260
Q

Why is there rouleaux formation of RBCs on blood smear?

A

increased serum protein decreases charge between RBCs

261
Q

Why is there primary AL amyloidosis in multiple myeloma?

A

Free light chains circulate in serum and deposit in tissues.

262
Q

Why is there proteinuria in multiple myeloma? What does this increase the risk for?

A

Free light chain is excreted in the urine as Bence Jones protein; deposition in kidney tubules leads to risk for renal failure (myeloma kidney).

263
Q

What is monoclonalgammopathy of undetermined significance?

A

Increased serum protein with M spike on SPEP; other features of multiple myeloma are absent (no lytic bone lesions, hypercalcemia, AL amyloid, or Bence Jones proteinuria)

264
Q

MGUS is common in what group of people?

A

elderly (seen in 5% of 70-year-old individuals);

265
Q

What are the odds of a patient with MGUS developing multiple myeloma?

A

1% of patients with MGUS develop multiple myeloma each year.

266
Q

What is Waldenstrom macroglobulinemia?

A

B-cell lymphoma with monoclonal IgM production

267
Q

What are the clinical features for waldenstrom macroglobulinemia?

A

1) Generalized lymphadenopathy, lytic bone lesions are absent 2) Increased serum protein with M spike (comprised of IgM) 3) Visual and neurologic deficits (e.g., retinal hemorrhage or stroke) IgM (large pentamer) causes serum hyperviscosity. 4) Bleeding

268
Q

Why is there bleeding in waldenstrom macroglobulinemia?

A

Viscous serum results in defective platelet aggregation

269
Q

What are the complications for waldenstrom macroglobulinemia treated with?

A

plasmapheresis, which removes IgM from the serum

270
Q

What are langerhans cells?

A

specialized dendritic cells found predominantly in the skin.

271
Q

What are langerhans cells derived from?

A

bone marrow monocytes

272
Q

What do langerhans cells present?

A

Present antigen to naive T cells

273
Q

What is langerhans cell histiocytosis?

A

it is a neoplastic proliferation of Langerhans cells

274
Q

What is seen on electron microscopy in langerhan cell histiocytosis?

A

Characteristic Birbeck (tennis racket) granules are seen on electron microscopy;

275
Q

What is langerhan cell histiocytosis immunochemistry?

A

cells are CDla+ and S100+

276
Q

What is Letterer-Siwe disease?

A

Malignant proliferation of Langerhans cells

277
Q

What is the classic presentation of Letterer-Siwe?

A

it is a skin rash and cystic skeletal defects in an infant (< 2 years old).

278
Q

Can Letterer-Siwe be fatal?

A

Multiple organs may be involved; rapidly fatal

279
Q

What is eosinophilic granuloma?

A

Benign proliferation of Langerhans cells in bone

280
Q

What is the classic presentation for eosinophilic granuloma?

A

it is a pathologic fracture in an adolescent; skin is not involved

281
Q

What does biopsy of eosinophilic granuloma show?

A

Langerhans cells with mixed inflammatory cells, including numerous eosinophils

282
Q

What is Hand-Schuller-Christian disease?

A

Malignant proliferation of Langerhans cells

283
Q

What is the classic presentation of Hand-Schuller-Christian disease?

A

it is scalp rash, lytic skull defects, diabetes insipidus, and exophthalmos in a child.